Type I interferon induced during chronic viral infection favors B-cell development in the thymus.

Chronic viral infections cause thymic involution yet the potential for broader, longer-term impact on thymic composition remains unexplored. Here we show that chronic, but not acute, lymphocytic choriomeningitis virus infection promotes a unique population of immature B cells in the thymus. We show that chronic viral infection promotes signals within the thymus, including the expression of B-cell activating factor (BAFF), that favor the maturation of this population as these cells acquire expression of CD19 and immunoglobulin M. Mechanistically, type I interferon (IFN-I), predominantly IFNß, signals to thymic hematopoietic cells, strongly delaying T-cell development at the earliest precursor stage. Furthermore, IFN-I signaling to the nonhematopoietic compartment provides a second signal essential to favor B-cell differentiation and maturation within the thymus. Importantly, chronic infection yields changes in the B-cell population for at least 50 days following infection, long after thymic atrophy has subsided. Thus, the inflammatory milieu induced by chronic viral infection has a profound, and long-lasting, effect on thymic composition leading to the generation of a novel population of thymic B cells.

Tetrabromobisphenol A exerts thyroid disrupting effects but has little overt impact on postnatal brain development and neurobehaviors in mice.

Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant. There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals, but different results were also reported, along with inconsistent reports regarding its neurotoxicity. Here, we investigated thyroid disrupting effects and neurotoxicity of TBBPA (5, 50, 500 µg/(kg·day)) to male mice following maternal and direct exposure through drinking water, with the anti-thyroid drug propylthiouracil (PTU) as the positive control. On postnatal day (PND) 15, we expectedly observed severe thyroid compensatory hyperplasia and cerebellar developmental retardation in PTU-treated pups. The highest dose of TBBPA also caused thyroid histological alteration but had no effects on cerebellar development in terms of Purkinje cell morphology and the thickness of the internal granular layer and the molecular layer of the cerebellum. During puberty and adulthood, the thyroid morphological alterations became more pronounced in the TBBPA-treated animals, accompanied by decreased serum thyroid hormone levels. Furthermore, the 50 and 500 µg/(kg·day) TBBPA groups showed a significant decrease in the serum level of serotonin, a neurotransmitter associated with anxiety behaviors. Correspondingly, the highest dose group displayed anxiety-like behaviors in the elevated plus-maze test on PND 35, but this neurobehavioral alteration disappeared on PND 56. Moreover, no changes in neurobehavioral parameters tested were found in TBBPA-treated animals at puberty and adulthood. Altogether, all observations show that TBBPA can exert thyroid disrupting effects but has little overt impact on brain development and neurobehaviors in mice, suggesting that thyroid disruption does not necessarily cause overtly adverse neurodevelopmental outcomes.

Infiltrating myeloid cell-derived properdin markedly promotes microglia-mediated neuroinflammation after ischemic stroke.

BACKGROUND: Emerging evidence has shown that myeloid cells that infiltrate into the peri-infarct region may influence the progression of ischemic stroke by interacting with microglia. Properdin, which is typically secreted by immune cells such as neutrophils, monocytes, and T cells, has been found to possess damage-associated molecular patterns (DAMPs) properties and can perform functions unrelated to the complement pathway. However, the role of properdin in modulating microglia-mediated post-stroke neuroinflammation remains unclear. METHODS: Global and conditional (myeloid-specific) properdin-knockout mice were subjected to transient middle cerebral artery occlusion (tMCAO). Histopathological and behavioral tests were performed to assess ischemic brain injury in mice. Single-cell RNA sequencing and immunofluorescence staining were applied to explore the source and the expression level of properdin. The transcriptomic profile of properdin-activated primary microglia was depicted by transcriptome sequencing. Lentivirus was used for macrophage-inducible C-type lectin (Mincle) silencing in microglia. Conditioned medium from primary microglia was administered to primary cortex neurons to determine the neurotoxicity of microglia. A series of cellular and molecular biological techniques were used to evaluate the proinflammatory response, neuronal death, protein-protein interactions, and related signaling pathways, etc. RESULTS: The level of properdin was significantly increased, and brain-infiltrating neutrophils and macrophages were the main sources of properdin in the ischemic brain. Global and conditional myeloid knockout of properdin attenuated microglial overactivation and inflammatory responses at the acute stage of tMCAO in mice. Accordingly, treatment with recombinant properdin enhanced the production of proinflammatory cytokines and augmented microglia-potentiated neuronal death in primary culture. Mechanistically, recombinant properdin served as a novel ligand that activated Mincle receptors on microglia and downstream pathways to drive primary microglia-induced inflammatory responses. Intriguingly, properdin can directly bind to the microglial Mincle receptor to exert the above effects, while Mincle knockdown limits properdin-mediated microglial inflammation. CONCLUSION: Properdin is a new medium by which infiltrating peripheral myeloid cells communicate with microglia, further activate microglia, and exacerbate brain injury in the ischemic brain, suggesting that targeted disruption of the interaction between properdin and Mincle on microglia or inhibition of their downstream signaling may improve the prognosis of ischemic stroke.

A strategy of vascular-targeted therapy for liver fibrosis.

BACKGROUND AND AIMS: No effective treatments are available for liver fibrosis. Angiogenesis is deeply involved in liver fibrogenesis. However, current controversial results suggest it is difficult to treat liver fibrosis through vascular targeting. There are three different microvessels in liver: portal vessels, liver sinusoids, and central vessels. The changes and roles for each of the three different vessels during liver fibrogenesis are unclear. We propose that they play different roles during liver fibrogenesis, and a single vascular endothelial cell (EC) regulator is not enough to fully regulate these three vessels to treat liver fibrosis. Therefore, a combined regulation of multiple different EC regulatory signaling pathway may provide new strategies for the liver fibrosis therapy. Herein, we present a proof-of-concept strategy by combining the regulation of leukocyte cell-derived chemotaxin 2 (LECT2)/tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 signaling with that of vascular endothelial growth factor (VEGF)/recombinant VEGF (rVEGF) signaling. APPROACH AND RESULTS: The CCl4 -induced mouse liver fibrosis model and NASH model were both used. During fibrogenesis, vascular changes occurred at very early stage, and different liver vessels showed different changes and played different roles: decreased portal vessels, increased sinusoid capillarization and the increased central vessels the increase of portal vessels alleviates liver fibrosis, the increase of central vessels aggravates liver fibrosis, and the increase of sinusoid capillarization aggravates liver fibrosis. The combinational treatment of adeno-associated viral vector serotype 9 (AAV9)-LECT2-short hairpin RNA (shRNA) and rVEGF showed improved therapeutic effects, but it led to serious side effects. The combination of AAV9-LECT2-shRNA and bevacizumab showed both improved therapeutic effects and decreased side effects. CONCLUSIONS: Liver vascular changes occurred at very early stage of fibrogenesis. Different vessels play different roles in liver fibrosis. The combinational treatment of AAV9-LECT2-shRNA and bevacizumab could significantly improve the therapeutic effects on liver fibrosis.

NR4A3 Mediates Thymic Negative Selection.

Central tolerance aims to limit the production of T lymphocytes bearing TCR with high affinity for self-peptide presented by MHC molecules. The accumulation of thymocytes with such receptors is limited by negative selection or by diversion into alternative differentiation, including T regulatory cell commitment. A role for the orphan nuclear receptor NR4A3 in negative selection has been suggested, but its function in this process has never been investigated. We find that Nr4a3 transcription is upregulated in postselection double-positive thymocytes, particularly those that have received a strong selecting signal and are destined for negative selection. Indeed, we found an accumulation of cells bearing a negative selection phenotype in NR4A3-deficient mice as compared with wild-type controls, suggesting that Nr4a3 transcriptional induction is necessary to limit accumulation of self-reactive thymocytes. This is consistent with a decrease of cleaved caspase-3+-signaled thymocytes and more T regulatory and CD4+Foxp3-HELIOS+ cells in the NR4A3-deficient thymus. We further tested the role for NR4A3 in negative selection by reconstituting transgenic mice expressing the OVA Ag under the control of the insulin promoter with bone marrow cells from OT-I Nr4a3 +/+ or OT-I Nr4a3 -/- mice. Accumulation of autoreactive CD8 thymocytes and autoimmune diabetes developed only in the absence of NR4A3. Overall, our results demonstrate an important role for NR4A3 in T cell development.

CD5 levels define functionally heterogeneous populations of naïve human CD4+ T cells.

Studies in murine models show that subthreshold TCR interactions with self-peptide are required for thymic development and peripheral survival of naïve T cells. Recently, differences in the strength of tonic TCR interactions with self-peptide, as read-out by cell surface levels of CD5, were associated with distinct effector potentials among sorted populations of T cells in mice. However, whether CD5 can also be used to parse functional heterogeneity among human T cells is less clear. Our study demonstrates that CD5 levels correlate with TCR signal strength in human naïve CD4+ T cells. Further, we describe a relationship between CD5 levels on naïve human CD4+ T cells and binding affinity to foreign peptide, in addition to a predominance of CD5hi T cells in the memory compartment. Differences in gene expression and biases in cytokine production potential between CD5lo and CD5hi naïve human CD4+ T cells are consistent with observations in mice. Together, these data validate the use of CD5 surface levels as a marker of heterogeneity among human naïve CD4+ T cells with important implications for the identification of functionally biased T- cell populations that can be exploited to improve the efficacy of adoptive cell therapies.

The ICOS-ICOSL pathway tunes thymic selection.

Negative selection of developing T cells plays a significant role in T-cell tolerance to self-antigen. This process relies on thymic antigen-presenting cells which express both self-antigens and cosignaling molecules. Inducible T-cell costimulator (ICOS) belongs to the CD28 family of cosignaling molecules and binds to ICOS ligand (ICOSL). The ICOS signaling pathway plays important roles in shaping the immune response to infections, but its role in central tolerance is less well understood. Here we show that ICOSL is expressed by subsets of thymic dendritic cells and medullary thymic epithelial cells as well as thymic B cells. ICOS expression is upregulated as T cells mature in the thymus and correlates with T-cell receptor signal strength during thymic selection. We also provide evidence of a role for ICOS signaling in mediating negative selection. Our findings suggest that ICOS may fine-tune T-cell receptor signals during thymic selection contributing to the generation of a tolerant T-cell population.

Effects of postnatal exposure to tetrabromobisphenol A on testis development in mice and early key events.

Whether or not tetrabromobisphenol A (TBBPA) has reproductive developmental toxicity remains controversial. Here, we evaluated the effects of postnatal TBBPA exposure of dams (before weaning) and pups through drinking water (15, 150, 1500 ng/mL) on testis development in mice. On postnatal day (PND) 56, we found that TBBPA exerted little effects on testis weight, anogenital distance, sperm parameters, and the serum testosterone level, but resulted in dose-dependent reductions in the seminiferous tubule area coupled with decreased Sertoli cells and spermatogonia and the number of stage VII-VIII seminiferous tubules, and cytoskeleton damage in Sertoli cells, along with down-regulated expression of marker genes for Sertoli cells, spermatogonia and spermatocyte. Further study revealed that the reduced tubule area coupled decreased Sertoli cell and germ cell numbers and marker gene expression also occurred in TBBPA-treated testes on PND 7, along with reduced cell proliferation and disordered arrangement of Sertoli cell nuclei. On PND 15, most of these testicular alterations were still observed in TBBPA-treated males, and cytoskeleton damage in Sertoli cells became observable. All observations convincingly demonstrate that postnatal exposure to TBBPA disturbed testis development in early life and ultimately caused adverse outcomes in adult testes, and that cell proliferation inhibition, the reduction in the seminiferous tubule area coupled decreased Sertoli cell and germ cell numbers and marker gene expression, and cytoskeleton damage in Sertoli cells, are early events contributing to adverse outcomes in adult testes. Our study improves the understanding of reproductive developmental toxicity of TBBPA, highlighting its risk for human health.

Photosynthesis of winter wheat effectively reflected multiple physiological responses under short-term drought-rewatering conditions.

BACKGROUND: Based on the interrelationship among photosynthesis (Pn), water consumption and drought resistance physiology under water changes, this study aimed to explore whether easily measured Pn could be used to reflect the physiological state of winter wheat and soil moisture. The study was a greenhouse pot experiment, with three growth periods and four gradients of moisture. RESULTS: The instantaneous water use efficiency of wheat improved significantly under short-term regulated deficit irrigation conditions. The photosynthetic parameters could effectively reflect the level of soil moisture (receiver operating characteristic curve analysis, area under the curve = 0.683-0.988). There was a significant correlation between Pn and yield under drought and rewatering (P < 0.05). The water consumption of winter wheat was significantly reduced by 15.5% to 47.6% (P < 0.05) during drought owing to the reduction of stomatal conductance and transpiration rate (Tr). There was a significant linear relationship between Tr and daily water consumption (R2 > 0.745, P< 0.05). There was a significant quadratic linear relationship (R2 > 0.600, P < 0.05) between Pn and the drought resistance indicators. The protective effect of drought resistance physiology on Pn was more significant during drought than during rewatering. Among the four physiological indicators of drought resistance, the relationship between peroxidase activity and Pn was relatively close (grey relational analysis, GRO = 1). CONCLUSIONS: The photosynthetic parameters during conditions of short-term water changes could effectively reflect the status of soil moisture, water consumption, yield and drought resistance. A focus on Pn and the rational use of related relationships are conducive to the selection of drought-resistant varieties and developing refined agricultural management. © 2021 Society of Chemical Industry.

CD5 levels reveal distinct basal T-cell receptor signals in T cells from non-obese diabetic mice.

Type 1 diabetes in non-obese diabetic (NOD) mice occurs when autoreactive T cells eliminate insulin producing pancreatic ß cells. While extensively studied in T-cell receptor (TCR) transgenic mice, the contribution of alterations in thymic selection to the polyclonal T-cell pool in NOD mice is not yet resolved. The magnitude of signals downstream of TCR engagement with self-peptide directs the development of a functional T-cell pool, in part by ensuring tolerance to self. TCR interactions with self-peptide are also necessary for T-cell homeostasis in the peripheral lymphoid organs. To identify differences in TCR signal strength that accompany thymic selection and peripheral T-cell maintenance, we compared CD5 levels, a marker of basal TCR signal strength, on immature and mature T cells from autoimmune diabetes-prone NOD and -resistant B6 mice. The data suggest that there is no preferential selection of NOD thymocytes that perceive stronger TCR signals from self-peptide engagement. Instead, NOD mice have an MHC-dependent increase in CD4+ thymocytes and mature T cells that express lower levels of CD5. In contrast, T cell-intrinsic mechanisms lead to higher levels of CD5 on peripheral CD8+ T cells from NOD relative to B6 mice, suggesting that peripheral CD8+ T cells with higher basal TCR signals may have survival advantages in NOD mice. These differences in the T-cell pool in NOD mice may contribute to the development or progression of autoimmune diabetes.

Signal intensity ratio of draining vein on silent MR angiography as an indicator of high-flow arteriovenous shunt in brain arteriovenous malformation.

OBJECTIVES: To evaluate whether the signal intensity ratio (rSI) of the draining vein on silent MR angiography is correlated with arteriovenous (A-V) transit time on digital subtraction angiography (DSA), thereby identifying high-flow A-V shunt in brain arteriovenous malformation (BAVM), and to analyze whether the rSI and the characteristic of draining veins on silent MRA are associated with hemorrhage presentation. METHODS: Eighty-one draining veins of 46 participants with BAVM (mean age 33.2 ± 16.9 years) who underwent silent MRA and DSA were evaluated retrospectively. The correlation between the rSI of the draining vein on silent MRA and A-V transit time on DSA was examined. The AUC-ROC was obtained to evaluate the performance of the rSI in determining the presence of high-flow A-V shunt. The characteristics of draining veins with the maximum rSI (rSImax) were further compared between the hemorrhagic and non-hemorrhagic untreated BAVM. RESULTS: The rSI of each draining vein on silent MRA was significantly correlated with A-V transit time from DSA (r = -0.81, p < .001). The AUC-ROC was 0.89 for using the rSI to determine the presence of high-flow A-V shunt. A cut-off rSI value of 1.09 yielded a sensitivity of 82.4% and a specificity of 82.8%. The draining vein with rSImax and no ectasia was significantly more observed in the hemorrhagic group (p = 0.045). CONCLUSIONS: The rSI of the draining vein on silent MRA is significantly correlated with A-V transit time on DSA, and it can be used as an indicator of high-flow A-V shunt in BAVM. KEY POINTS: • The signal intensity ratio (rSI) of the draining vein on silent MRA significantly correlated with arteriovenous (A-V) transit time of brain arteriovenous malformation (BAVM) on digital subtraction angiography (DSA). • The area under the receiver operating characteristic curve (AUC) was 0.89 for using the rSI of draining veins to determine high-flow A-V shunt. • Draining veins with maximum rSI and no ectasia were significantly more observed in the hemorrhagic group of BAVM (p = 0.045).

PSMB11 Orchestrates the Development of CD4 and CD8 Thymocytes via Regulation of Gene Expression in Cortical Thymic Epithelial Cells.

T cell development depends on sequential interactions of thymocytes with cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells. PSMB11 is a catalytic proteasomal subunit present exclusively in cTECs. Because proteasomes regulate transcriptional activity, we asked whether PSMB11 might affect gene expression in cTECs. We report that PSMB11 regulates the expression of 850 cTEC genes that modulate lymphostromal interactions primarily via the WNT signaling pathway. cTECs from Psmb11 -/- mice 1) acquire features of medullary thymic epithelial cells and 2) retain CD8 thymocytes in the thymic cortex, thereby impairing phase 2 of positive selection, 3) perturbing CD8 T cell development, and 4) causing dramatic oxidative stress leading to apoptosis of CD8 thymocytes. Deletion of Psmb11 also causes major oxidative stress in CD4 thymocytes. However, CD4 thymocytes do not undergo apoptosis because, unlike CD8 thymocytes, they upregulate expression of chaperones and inhibitors of apoptosis. We conclude that PSMB11 has pervasive effects on both CD4 and CD8 thymocytes via regulation of gene expression in cTECs.

Tetrabromobisphenol A Disturbs Brain Development in Both Thyroid Hormone-Dependent and -Independent Manners in Xenopus laevis.

Although tetrabromobisphenol A (TBBPA) has been well proven to disturb TH signaling in both in vitro and in vivo assays, it is still unclear whether TBBPA can affect brain development due to TH signaling disruption. Here, we employed the T3-induced Xenopus metamorphosis assay (TIXMA) and the spontaneous metamorphosis assay to address this issue. In the TIXMA, 5-500 nmol/L TBBPA affected T3-induced TH-response gene expression and T3-induced brain development (brain morphological changes, cell proliferation, and neurodifferentiation) at premetamorphic stages in a complicated biphasic concentration-response manner. Notably, 500 nmol/L TBBPA treatment alone exerted a stimulatory effect on tadpole growth and brain development at these stages, in parallel with a lack of TH signaling activation, suggesting the involvement of other signaling pathways. As expected, at the metamorphic climax, we observed inhibitory effects of 50-500 nmol/L TBBPA on metamorphic development and brain development, which was in agreement with the antagonistic effects of higher concentrations on T3-induced brain development at premetamorphic stages. Taken together, all results demonstrate that TBBPA can disturb TH signaling and subsequently interfere with TH-dependent brain development in Xenopus; meanwhile, other signaling pathways besides TH signaling could be involved in this process. Our study improves the understanding of the effects of TBBPA on vertebrate brain development.

Low Concentrations of Tetrabromobisphenol A Disrupt Notch Signaling and Intestinal Development in in Vitro and in Vivo Models.

Tetrabromobisphenol A (TBBPA) was recently reported to upregulate Notch target gene expression in embryonic stem cells differentiating to neurons in vitro, implying activation on Notch signaling, a crucial signaling involved in multiple organ development and homeostasis.The present study aimed to determine whether TBBPA at low concentrations can disrupt Notch signaling in the intestine and subsequently its development using in vitro and in vivo models, given TBBPA uptake mainly via the intestine. In rat intestinal epithelium cells (IEC-6), an in vitro model for intestinal development and homeostasis, we found 5-500 nM TBBPA upregulated Notch-related gene expression and stimulated cell proliferation as well as the growth of microvilli in a linear concentration-dependent manner. When Notch inhibitor DAPT had no obvious effects on all end points, DAPT significantly antagonized all changes caused by TBBPA, indicating that TBBPA activated Notch signaling in IEC-6 cells and subsequently stimulated cell proliferation and differentiation. Then we employed Xenopus laevis, an ideal model species for intestinal development with the strong similarities to mammals, to further confirm the action of TBBPA in vivo. Expectedly, we observed the stimulatory effects of TBBPA on Notch signaling and cell proliferation and differentiation in X. laevis intestines, which agrees with the results in vitro. Antagonistic actions of Notch inhibitor DBZ on TBBPA-caused intestinal changes show that TBBPA affected intestinal development via disrupting Notch signaling. Interestingly, TBBPA stimulated cell differentiation into secretory cells, which is generally believed to be regulated by Wnt signaling, suggesting disruption of Wnt signaling besides Notch signaling. All the results for the first time demonstrate that TBBPA at low concentrations, including environmentally relevant concentrations, disrupt Notch signaling and subsequently affect intestinal development by altering cell proliferation and differentiation in vertebrates. Our study highlights the intestine as a new target of TBBPA and broaden our understanding of developmental toxicity of TBBPA.

The interaction of CaM7 and CNGC14 regulates root hair growth in Arabidopsis.

Oscillations in cytosolic free calcium determine the polarity of tip-growing root hairs. The Ca2+ channel cyclic nucleotide gated channel 14 (CNGC14) contributes to the dynamic changes in Ca2+ concentration gradient at the root hair tip. However, the mechanisms that regulate CNGC14 are unknown. In this study, we detected a direct interaction between calmodulin 7 (CaM7) and CNGC14 through yeast two-hybrid and bimolecular fluorescence complementation assays. We demonstrated that the third EF-hand domain of CaM7 specifically interacts with the cytosolic C-terminal domain of CNGC14. A two-electrode voltage clamp assay showed that CaM7 completely inhibits CNGC14-mediated Ca2+ influx, suggesting that CaM7 negatively regulates CNGC14-mediated calcium signaling. Furthermore, CaM7 overexpressing lines phenocopy the short root hair phenotype of a cngc14 mutant and this phenotype is insensitive to changes in external Ca2+ concentrations. We, thus, identified CaM7-CNGC14 as a novel interacting module that regulates polar growth in root hairs by controlling the tip-focused Ca2+ signal.

Alterations in the Thymic Selection Threshold Skew the Self-Reactivity of the TCR Repertoire in Neonates.

Neonatal and adult T cells differ in their effector functions. Although it is known that cell-intrinsic differences in mature T cells contribute to this phenomenon, the factors involved remain unclear. Given emerging evidence that the binding strength of a TCR for self-peptide presented by MHC (self-pMHC) impacts T cell function, we sought to determine whether altered thymic selection influences the self-reactivity of the TCR repertoire during ontogeny. We found that conventional and regulatory T cell subsets in the thymus of neonates and young mice expressed higher levels of cell surface CD5, a surrogate marker for TCR avidity for self-pMHC, as compared with their adult counterparts, and this difference in self-reactivity was independent of the germline bias of the neonatal TCR repertoire. The increased binding strength of the TCR repertoire for self-pMHC in neonates was not solely due to reported defects in clonal deletion. Rather, our data suggest that thymic selection is altered in young mice such that thymocytes bearing TCRs with low affinity for self-peptide are not efficiently selected into the neonatal repertoire, and stronger TCR signals accompany both conventional and regulatory T cell selection. Importantly, the distinct levels of T cell self-reactivity reflect physiologically relevant differences based on the preferential expansion of T cells from young mice to fill a lymphopenic environment. Therefore, differences in thymic selection in young versus adult mice skew the TCR repertoire, and the relatively higher self-reactivity of the T cell pool may contribute to the distinct immune responses observed in neonates.

Exploring and comparing two means of preparing and fractionating oligomeric proanthocyanidins from mangosteen pericarp: gel filtration chromatography and progressive solvent precipitation.

The preparation and fractionation of oligomeric proanthocyanidins (OPCs) are particularly important for the application of tannins in the biomedical field. By use of two different methods-gel filtration chromatography (GFC) with Sephadex LH-20 and progressive solvent precipitation-the OPCs were prepared and fractionated from mangosteen pericarp. The fractions were compared by reversed-phase and normal-phase high-performance liquid chromatography-electrospray ionization mass spectrometry and gel permeation chromatography. GFC directly purified oligomers (monomer to pentamer) with polydispersity values close to 1 and generated fractions with a higher level of total phenols (800.59 mg gallic acid equivalents per gram) but a lower yield (7.72%). Progressive solvent precipitation rapidly prepared and fractionated OPCs with a lower level of total phenols (609.57 mg gallic acid equivalents per gram) but a higher yield (24.74%) and higher polydispersity. Additionally, we found pronounced structural and quantitative differences among different tannin-rich fractions, and fractions obtained by GFC better reflected the structural diversity and complexity of OPCs from mangosteen pericarp. This study presents different ways of preparing and fractionating OPCs in the biomedical field.

Development of three-dimensional brain arteriovenous malformation model for patient communication and young neurosurgeon education.

PURPOSE: Rapid prototyping technology is used to fabricate three-dimensional (3D) brain arteriovenous malformation (AVM) models and facilitate presurgical patient communication and medical education for young surgeons. METHODS: Two intracranial AVM cases were selected for this study. Using 3D CT angiography or 3D rotational angiography images, the brain AVM models were reconstructed on personal computer and the rapid prototyping process was completed using a 3D printer. The size and morphology of the models were compared to brain digital subtraction arteriography of the same patients. 3D brain AVM models were used for preoperative patient communication and young neurosurgeon education. RESULTS: Two brain AVM models were successfully produced. By neurosurgeons' evaluation, the printed models have high fidelity with the actual brain AVM structures of the patients. The patient responded positively toward the brain AVM model specific to himself. Twenty surgical residents from residency programs tested the brain AVM models and provided positive feedback on their usefulness as educational tool and resemblance to real brain AVM structures. CONCLUSIONS: Patient-specific 3D printed models of brain AVM can be constructed with high fidelity. 3D printed brain AVM models are proved to be helpful in preoperative patient consultation, surgical planning and resident training.

Novel Natural Product- and Privileged Scaffold-Based Tubulin Inhibitors Targeting the Colchicine Binding Site.

Tubulin inhibitors are effective anticancer agents, however, there are many limitations to the use of available tubulin inhibitors in the clinic, such as multidrug resistance, severe side-effects, and generally poor bioavailability. Thus, there is a constant need to search for novel tubulin inhibitors that can overcome these limitations. Natural product and privileged structures targeting tubulin have promoted the discovery and optimization of tubulin inhibitors. This review will focus on novel tubulin inhibitors derived from natural products and privileged structures targeting the colchicine binding site on tubulin.

Safety Profile of TiO2-Based Photocatalytic Nanofabrics for Indoor Formaldehyde Degradation.

Anatase TiO2 nanoparticles (TNPs) are synthesized using the sol-gel method and loaded onto the surface of polyester-cotton (65/35) fabrics. The nanofabrics degrade formaldehyde at an efficiency of 77% in eight hours with visible light irradiation or 97% with UV light. The loaded TNPs display very little release from nanofabrics (~0.0%) during a standard fastness to rubbing test. Assuming TNPs may fall off nanofabrics during their life cycles, we also examine the possible toxicity of TNPs to human cells. We found that up to a concentration of 220 µg/mL, they do not affect viability of human acute monocytic leukemia cell line THP-1 macrophages and human liver and kidney cells.