Affinity purification of mAb from serum-containing hybridoma culture supernatant through a novel nanobody that discriminates mouse IgG from bovine IgG by recognizing the mouse kappa constant region (mCK).

When purifying mAb from serum-containing hybridoma culture supernatant, it is essential that mouse IgG remains free from contaminations of bovine IgG. However, the broadly used Protein A resin cannot achieve this goal due to binding between both mouse and bovine IgG. Here, a novel nanobody-based affinity purification magnetic beads that discriminates mouse IgG from bovine IgG was developed. To bind all subtypes of mouse IgG (IgG1, IgG2a, IgG2b and IgG3) that contain the kappa light chain, mCK (mouse kappa constant region)-specific nanobody binders were selected from an immune phage display VHH library; this library was constructed with peripheral blood mononuclear cells (PBMCs), which were collected from Bactrian camels immunized with a mix of intact mouse IgGs (IgG1, IgG2a, IgG2b and IgG3). A novel clone that exhibited a higher expression level and a higher binding affinity was selected (4E6). Then, the 4E6 nanobody in the format of VHH-hFC (human Fc) was conjugated on magnetic beads with a maximal binding capacity of 15.41±0.69 mg mouse IgG/mL beads. Furthermore, no bovine IgG could be copurified from hybridoma culture supernatant with immunomagnetic beads. This approach is valuable for the large-scale in vitro production of highly pure antibodies by hybridoma cells.

Flexible light-stimulated artificial synapse based on detached (In,Ga)N thin film for neuromorphic computing.

Because of wide range of applications, the flexible artificial synapse is an indispensable part for next-generation neural morphology computing. In this work, we demonstrate a flexible synaptic device based on a lift-off (In,Ga)N thin film successfully. The synaptic device can mimic the learning, forgetting, and relearning functions of biological synapses at both flat and bent states. Furthermore, the synaptic device can simulate the transition from short-term memory to long-term memory successfully under different bending conditions. With the high flexibility, the excitatory post-synaptic current of the bent device only shows a slight decrease, leading to the high stability. Based on the experimental conductance for long-term potentiation and depression, the simulated three-layer neural network can achieve a high recognition rate up to 90.2%, indicating that the system comprising of flexible synaptic devices could have a strong learning-memory capability. Therefore, this work has a great potential for the development of wearable intelligence devices and flexible neuromorphic systems.

Yellow pigments produced by oxidative oligomerization of dihydrochalcone glucoside and the reaction mechanism.

From the dried leaves of Lithocarpus polystachyus, yellow pigments, lithocarputins B (11) and C (12), were isolated with a colorless dihydrochalcone dimer, lithocarputin A (10). The pigments 11 and 12 are dimeric dihydrochalcone glycosides with bicyclo[3.2.1]octane structures. Each pigment is a diastereomeric mixture with enantiomeric aglycones that could not be separated. The production mechanisms of the pigments were proposed based on the in vitro enzymatic preparation from trilobatin (1), the major dihydrochalcone glucoside of L. polystachyus. The majority of the pigments in the dried leaves were the oligomers of the dihydrochalcone glycosides generated by a mechanism similar to dimerization. The pigments are probably artifacts produced in the drying process. This is the first report disclosing a detailed chemical mechanism for pigment formation from dihydrochalcone.

Isolation of Two New Phenolic Glycosides from Castanopsis chinensis Hance by Combined Multistep CC and HSCCC Separation and Evaluation of Their Antioxidant Activity.

The characteristics of high polarity and susceptibility to oxidation in phenolic glycosides increase the difficulty of their separation from natural products. In the present study, two new phenolic glycosides with similar structures were isolated from Castanopsis chinensis Hance using a combination of multistep CC and high-speed countercurrent chromatography. Preliminary separation of the target fractions was carried out by Sephadex LH-20 chromatography (100-0% EtOH in H2O). High-speed countercurrent chromatography with an optimized solvent system of N-Hexane/Ethyl acetate/Methanol/Water (1:6:3:4, v/v/v/v) with a satisfactory stationary phase retention and separation factor was used for further separation and purification of the phenolic glycosides. Consequently, two new phenolic glycoside compounds were obtained with purities of 93.0% and 95.7%. 1D-NMR and 2D-NMR spectroscopy, mass spectrometry, and optical rotation were employed to identify their structures, which were assigned as chinensin D and chinensin E. The antioxidant and α-glucosidase inhibitory activities of these two compounds were evaluated using a DPPH antioxidant assay and a α-glucosidase inhibitory assay. Both compounds showed good antioxidant activity with IC50 values of 54.5 ± 0.82 µg/mL and 52.5 ± 0.47 µg/mL. The α-glucosidase inhibitory activity of the compounds was poor. The successful isolation and structure identification of the two new compounds provides materials not only for a systematic isolation method of phenolic glycosides with similar structures, but also for the screening of antioxidants and enzyme inhibitors.

Identification of Unstable Ellagitannin Metabolites in the Leaves of Quercus dentata by Chemical Derivatization.

The identification of unstable metabolites of ellagitannins having ortho-quinone structures or reactive carbonyl groups is important to clarify the biosynthesis and degradation of ellagitannins. Our previous studies on the degradation of vescalagin, a major ellagitannin of oak young leaves, suggested that the initial step of the degradation is regioselective oxidation to generate a putative quinone intermediate. However, this intermediate has not been identified yet. In this study, young leaves of Quercus dentata were extracted with 80% acetonitrile containing 1,2-phenylenediamine to trap unstable ortho-quinone metabolites, and subsequent chromatographic separation afforded a phenazine derivative of the elusive quinone intermediate of vescalagin. In addition, phenylenediamine adducts of liquidambin and dehydroascorbic acid were obtained, which is significant because liquidambin is a possible biogenetic precursor of C-glycosidic ellagitannins and ascorbic acid participates in the production of another C-glycosidic ellagitannin in matured oak leaves.

The complete chloroplast genome sequence of Castanopsis fordii Hance (Fagaceae).

Castanopsis fordii Hance 1884 is a typical evergreen broad-leaved forest plant in the south subtropical and middle subtropical regions of China. It has high utilization value in wood production and soil erosion protection. Here, we first reported and characterized the complete chloroplast (cp) genome sequence of C. fordii based on Illumina paired-end sequencing data. The complete cp genome sequence of C. fordii was 160,853 base pairs (bp) in length which contained two inverted repeats (IRs) of 25,699 bp separated by a large single-copy (LSC) and a small single copy (SSC) of 90,474 bp and 18,981 bp, respectively. The cpDNA contained 129 genes, comprising 85 protein-coding genes, 36 tRNA genes, 8 rRNA genes. The overall GC content of the plastome was 36.8%. Phylogenetic analysis base on 14 chloroplast genomes indicated that C. fordii was closely related to the species C. tibetana and C. concinna in Fagaceae.

Two new isoflavones from the barks of Dalbergia hancei Benth.

Two new isoflavone compounds, Dalhancei A (1) and Dalhancei B (2), along with a known compound epicatechin (3) were isolated from 80% methanol extract of the barks of Dalbergia hancei Benth. The structures of compounds 1-3 were elucidated by comparison with the literature and physical data analysis, including optical rotation, MS, 1D and 2D NMR spectra. Compounds 1 and 2 showed weak inhibitory activity against tyrosinase at 16.22 mmol/L, with inhibition rates of 42.23 ± 0.18% and 45.68 ± 0.17%, respectively; compound 1 exhibited weak inhibitory activity against α-glucosidase with the inhibition rate of 43.72 ± 0.22% at 5.41 mmol/L, compounds 2 and 3 had better α-glucosidase inhibitory activity than compound 1 with IC50 values of 0.90 ± 0.18 and 0.41 ± 0.17 mmol/L, respectively.

Two truxinate derivatives and a phenyldilactone from the leaves of Castanopsis eyrei.

Phytochemical investigation of the Leaves of Castanopsis eyrei led to the isolation of two new natural truxinate derivatives and a new phenyldilactone. The structures of the new natural compounds were determined by spectroscopic methods and chemical evidence as 3,3',4,4'-tetrahydroxy-ß-truxillic acid (1), 3,3',4,4'-tetrahydroxy-δ-truxillic acid (2), 3'-hydroxymaysedilactone A (3). Establishment of a Caenorhabditis elegans lipid metabolism model using GFP and mCherry fluorescently labeled lipid droplets to screen compound 3 for its activity in reducing lipid accumulation.

Barth Syndrome: Psychosocial Impact and Quality of Life Assessment.

BACKGROUND: Barth syndrome (BTHS) is a rare X-linked genetic disease that affects multiple systems and leads to complex clinical manifestations. Although a considerable amount of research has focused on the physical aspects of the disease, less has focused on the psychosocial impact and quality of life (QoL) in BTHS. METHODS: The current study investigated caregiver- (n = 10) and self-reported (n = 16) psychological well-being and QoL in a cohort of BTHS-affected patients and families. Participants completed the depression and anxiety components of the Patient-Reported Outcomes Information System (PROMIS) Short Form 8A and Health-related quality of life (HRQoL) surveys at enrollment and again during a follow-up period ranging from 6 to 36 months after baseline. RESULTS: Quality of life changed significantly over time and the various domains with some improvement and some decline. Among the available caregiver-patient dyad data, there was a trend toward discordance between caregiver and self-reported outcomes. Most notably, patients reported improvement in HRQoL, while caregivers reported declines. This suggests that there may be differences in perceived quality of life between the patients and parents, though our study is limited by small sample size. CONCLUSION: Our study provides valuable insights into the impacts of psychosocial and mental health aspects of BTHS. Implications of these findings include incorporating longitudinal assessment of QoL and screening for psychological symptoms in BTHS care to identify interventions that may drastically impact health status and the course of the disease.

Triterpene hexahydroxydiphenoyl ester and phenol glucosides from the leaves of Castanopsis eyrie (Champ. ex Benth.) Hutch.

As a part of our systematic study on Castanopsis genus (Fagaceae), one new triterpene hydrolysable tannin (1) and two new phenol glucosides (2 and 3) were isolated from the leaves of Castanopsis eyrei (Champ. ex Benth.) Hutch. Compound 1 was identified as a triterpene hexahydroxydiphenoyl (HHDP) ester. This type of compounds has only been isolated from Castanopsis genus. The structures of 1-3 were elucidated by the combination of spectroscopic analysis (MS, 1 D and 2 D NMR) and chemical evidence.

Structural Characterization and Assessment of Anti-Inflammatory Activities of Polyphenols and Depsidone Derivatives from Melastoma malabathricum subsp. normale.

The roots of Melastoma malabathricum subsp. normale (D. Don) Karst. Mey have been used in traditional ethnic medicine systems in China to treat inflammation-triggered ailments, such as trauma, toothache, and fever. Therefore, the aim of this study is to screen for compounds with anti-inflammatory activity in the title plant. The extract of M. malabathricum subsp. normale roots was separated using various chromatographic methods, such as silica gel, ODS C18, MCI gel, and Sephadex LH-20 column chromatography, as well as semi-preparative HPLC. One new complex tannin, named whiskey tannin D (1), and an undescribed tetracyclic depsidone derivative, named guanxidone B (2), along with nine known polyphenols (2-10) and three known depsidone derivatives (12-14) were obtained from this plant. The structures of all compounds were elucidated by extensive NMR and CD experiments in conjunction with HR-ESI-MS data. All these compounds were isolated from this plant for the first time. Moreover, compounds 1-4, 8, and 10-14 were obtained for the first time from the genus Melastoma, and compounds 1, 2, and 11-14 have not been reported from the family Melastomataceae. This is the first report of complex tannin and depsidone derivatives from M. malabathricum subsp. normale, indicating their chemotaxonomic significance to this plant. Compounds 1-12 were investigated for their anti-inflammatory activities on the production of the nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and compounds 1, 11, and 12 showed anti-inflammatory activities with IC50 values of 6.46 ± 0.23 µM, 8.02 ± 0.35 µM, and 9.82 ± 0.43 µM, respectively. The structure-activity relationship showed that the catechin at glucose C-1 in ellagitannin was the key to its anti-inflammatory activity, while CH3O- at C-16 of aromatic ring A in depsidone derivatives had little effect on its anti-inflammatory activity. The study of structure-activity relationships is helpful to quickly discover new anti-inflammatory drugs. The successful isolation and structure identification of these compounds, especially complex tannin 1, not only provide materials for the screening of anti-inflammatory compounds, but also provide a basis for the study of chemical taxonomy of the genus Melastoma.

Three new compounds from the leaves of Castanopsis tibetana Hance.

Three new compounds (6S,9S)-6'-galloyl-roseoside (1), purpurogallin ethyl carboxylate (2), and tibetana A (3) were isolated from 80% methanol extract of the leaves of Castanopsis tibetana Hance. Their structures were elucidated based on comprehensive spectroscopic methods and chemical data, including optical rotation, UV, MS, 1 D and 2 D NMR spectra. Compounds 1 and 3 were evaluated for their α-glucosidase inhibitory activity, pancreatic lipase inhibitory activity, and tyrosinase inhibitory activity.

Selfish parents, parenting practices, and psychopathic traits in children.

Parental personality and parenting behavior have been associated with the development of psychopathic traits in offspring. However, no study has examined the effect of parental dispositional selfishness on the development of psychopathic traits in offspring, and the potential mechanism underlying this relationship. To address this issue, parents' reports on their dispositional selfishness, negative and positive parenting behavior, and child's psychopathic traits were collected for a group of children from the community (n = 118, 47% male, mean age = 14.1 years). Results showed that parental selfishness was associated with grandiose-manipulative (GM), daring-impulsive (DI), and callous-unemotional (CU) traits in children. In addition, the egocentric selfishness-GM relationship was indirectly mediated by parenting behavior including lack of involvement, poor monitoring, and inconsistent discipline, whereas the association with CU traits was directly mediated by lack of involvement. These effects remained significant after controlling for child's sex, age, race, social adversity, and a prior measure of psychopathic traits. Findings provide initial empirical evidence on the effect of parental selfishness on a child's psychopathic traits, and further support to the proposition that distinct etiology may underlie different dimensions of psychopathic traits.

Structural Characterization and Assessment of Anti-Inflammatory and Anti-Tyrosinase Activities of Polyphenols from Melastoma normale.

Polyphenols, widely distributed in the genus Melastoma plants, possess extensive cellular protective effects such as anti-inflammatory, anti-tyrosinase, and anti-obesity, which makes it a potential anti-inflammatory drug or enzyme inhibitor. Therefore, the aim of this study is to screen for the anti-inflammatory and enzyme inhibitory activities of compounds from title plant. Using silica gel, MCI, ODS C18, and Sephadex LH-20 column chromatography, as well as semipreparative HPLC, the extract of Melastoma normale roots was separated. Four new ellagitannins, Whiskey tannin C (1), 1-O-(4-methoxygalloyl)-6-O-galloyl-2,3-O-(S)-hexahydroxydiphenoyl-ß-d-glucose (2), 1-O-galloyl-6-O-(3-methoxygalloyl)-2,3-O-(S)-hexahydroxydiphenoyl-ß-d-glucose (3), and 1-O-galloyl-6-O-vanilloyl-2,3-O-(S)-hexahydroxydiphenoyl-ß-d-glucose (4), along with eight known polyphenols were firstly obtained from this plant. The structures of all isolates were elucidated by HRMS, NMR, and CD analyses. Using lipopolysaccharide (LPS)-stimulated RAW2 64.7 cells, we investigated the anti-inflammatory activities of compounds 1-4, unfortunately, none of them exhibit inhibit nitric oxide (NO) production, their IC50 values are all > 50 µM. Anti-tyrosinase activity assays was done by tyrosinase inhibition activity screening model. Compound 1 showed weak tyrosinase inhibitory activity with IC50 values of 426.02 ± 11.31 µM. Compounds 2-4 displayed moderate tyrosinase inhibitory activities with IC50 values in the range of 124.74 ± 3.12-241.41 ± 6.23 µM. The structure-activity relationships indicate that hydroxylation at C-3', C-4', and C-3 in the flavones were key to their anti-tyrosinase activities. The successful isolation and structure identification of ellagitannin provide materials for the screening of anti-inflammatory drugs and enzyme inhibitors, and also contribute to the development and utilization of M. normale.

Ellagitannin Digestion in Moth Larvae and a New Dimeric Ellagitannin from the Leaves of Platycarya strobilacea.

Ellagitannins (ETs) are plant polyphenols with various health benefits. Recent studies have indicated that the biological activities of ETs are attributable to their degradation products, including ellagic acid and its gut microflora metabolites, such as urolithins. Insect tea produced in the Guangxi region, China, is made from the frass of moth larvae that feed on the ET-rich leaves of Platycarya strobilacea. Chromatographic separation of the Guangxi insect tea showed that the major phenolic constituents are ellagic acid, brevifolin carboxylic acid, gallic acid, brevifolin, and polymeric polyphenols. Chemical investigation of the feed of the larvae, the fresh leaves of P. strobilacea, showed that the major polyphenols are ETs including pedunculagin, casuarictin, strictinin, and a new ET named platycaryanin E. The new ET was confirmed as a dimer of strictinin having a tergalloyl group. The insect tea and the leaves of P. strobilacea contained polymeric polyphenols, both of which were shown to be composed of ETs and proanthocyanidins by acid hydrolysis and thiol degradation. This study clarified that Guangxi insect tea contains ET metabolites produced in the digestive tract of moth larvae, and the metabolites probably have higher bioavailabilities than the original large-molecular ETs of the leaves of P. strobilacea.

Ellagitannins and Oligomeric Proanthocyanidins of Three Polygonaceous Plants.

The aim of this study was to characterize hydrolyzable tannins in Polygonaceous plants, as only a few plants have previously been reported to contain ellagitannins. From Persicaria chinensis, a new hydrolyzable tannin called persicarianin was isolated and characterized to be 3-O-galloyl-4,6-(S)-dehydrohexahydroxydiphenoyl-d-glucose. Interestingly, acid hydrolysis of this compound afforded ellagic acid, despite the absence of a hexahydroxydiphenoyl group. From the rhizome of Polygonum runcinatum var. sinense, a large amount of granatin A, along with minor ellagitannins, helioscpoinin A, davicratinic acids B and C, and a new ellagitannin called polygonanin A, were isolated. Based on 2D nuclear magnetic resonance (NMR) spectroscopic examination, the structure of polygonanin A was determined to be 1,6-(S)-hexahydroxydiphenoyl-2,4-hydroxychebuloyl-ß-d-glucopyranose. These are the second and third hydrolyzable tannins isolated from Polygonaceous plants. In addition, oligomeric proanthocyanidins of Persicaria capitatum and P. chinensis were characterized by thiol degradation. These results suggested that some Polygonaceous plants are the source of hydrolyzable tannins not only proanthocyanidins.

Gray matter asymmetry in the orbitofrontal cortex in relation to psychopathic traits in adolescents.

BACKGROUND: Structural abnormalities in the orbitofrontal cortex (OFC) of incarcerated psychopaths have been well documented. However, the neural correlates of psychopathic traits in younger and nonclinical samples remain poorly understood. AIM: The present study aimed to examine the structural brain asymmetry in the OFC in relation to dimensions of psychopathic traits in adolescents from the community. METHOD: In 29 youths from the community, childhood psychopathic traits including narcissism, impulsivity, and callous-unemotional traits were assessed when they were 7- to 10 years old (Time 1), and their gray matter (GM) volumes were measured using structural Magnetic Resonance Imaging when they were 10- to 14 years old (Time 2). RESULTS: After controlling for age, sex, IQ, pubertal stage, and whole-brain volumes, callous-unemotional traits were associated with right-left asymmetry in the medial OFC (mOFC), that is, smaller right mOFC GM as compared to the left. Impulsivity was associated with left-right asymmetry in the mOFC, that is, smaller left mOFC than the right. Narcissism was not associated with any GM asymmetry measure. No significant association was found for the lateral OFC, amygdala, caudate and putamen. CONCLUSION: The present findings provide further support that dimensions of psychopathic traits may have distinct neurobiological correlates.

Rational Designed Mixed-Conductive Sulfur Cathodes for All-Solid-State Lithium Batteries.

All-solid-state lithium-sulfur batteries (ASSLSBs) hold great promise for safe and high-energy-density energy storage. However, developing high-performance sulfur cathodes has been proven difficult due to low electronic and ionic conductivities and large volume change of sulfur during charge and discharge. Here, we reported an approach to synthesize sulfur cathodes with a mixed electronic and ionic conductivity by infiltrating a solution consisting of Li3PS4 (LPS) solid electrolyte and S active material into a mesoporous carbon (CMK-3). This approach leads to a uniform dispersion of amorphous Li3PS7 (L3PS) catholyte in an electronically conductive carbon matrix, enabling high and balanced electronic/ionic conductivities in the cathode composite. The inherent porous structure of CMK-3 also helps to accommodate the strain/stress generated during the expansion and shrinkage of the active material. In sulfide-based all-solid-state batteries with Li metal as the anode, this cathode composite delivered a high capacity of 1025 mAh g-1 after 50 cycles at 60 °C at 1/8C. This work highlights the important role of high and balanced electronic and ionic conductivities in developing high-performance sulfur cathodes for ASSLSBs.

Aß monomer induces phosphorylation of Tau at Ser-214 through ß2AR-PKA-JNK signaling pathway.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with synaptic dysfunction, pathological accumulation of ß-amyloid peptide 1-42 (Aß1-42 ), and neuronal loss. The self-association of Aß1-42 monomers (Aß-M) into soluble oligomers seems to be crucial for the development of neurotoxicity. Previous publications have shown that Aß oligomers and dimers might play key roles in inducing AD. The role of Aß-M was rarely investigated and still unclear in AD. To understand the effects of Aß-M on neurons and other cell types in the brain could be the key to understand its function. In our study, we found that Aß-M expression slowly induced cell apoptosis within 48 hours after transfection, ß2 adrenergic receptor (ß2AR) interacted with Aß-M in the pull-down and the yeast two-hybrid assays, and Aß-M played a major role in inducing phosphorylation of Tau at Ser-214, c-Jun N-terminal kinase (JNK) at Thr-183/Tyr-185, p70 ribosomal protein S6 kinase (p70S6K) at Thr-389. We also discovered that ß2AR, G protein-coupled receptor kinase 2 (GRK2), and protein kinase A (PKA) mediated the phosphorylation of Tau and JNK. Aß-M induced phosphorylation of Tau at Ser-214 through both ß2AR-cAMP/PKA-JNK and ß2AR-GRK signaling pathways. Mitogen-activated protein kinase kinase (MEK) mediated the phosphorylation of p70S6K induced by Aß-M.

Altered growth trajectory in children born to mothers with gestational diabetes mellitus and preeclampsia.

PURPOSE: Gestational diabetes mellitus (GDM) and preeclampsia are leading causes of mortality and morbidity in mothers and children. High childhood body mass index (BMI) is among their myriad of negative outcomes. However, little is known about the trajectory of the child BMI exposed to GDM and co-occurring preeclampsia from early to mid-childhood. This study examined the independent and joint impact of GDM and preeclampsia on childhood BMI trajectory. METHODS: A population-based sample of 356 mothers were recruited from OB/GYN clinics in New York. Their children were then followed annually from 18 to 72 months. Maternal GDM and preeclampsia status were obtained from medical records. Child BMI was calculated based on their height and weight at annual visits. RESULTS: Hierarchical Linear Modeling was used to evaluate the trajectories of child BMI exposed to GDM and preeclampsia. BMI trajectory by GDM decreased (t ratio = - 2.24, [Formula: see text]0.45, 95% CI - 0.05-0.95, p = 0.07), but the trajectory by preeclampsia increased over time (t ratio = 3.153,[Formula: see text]0.65, 95% CI 0.11-1.18, p = 0.002). Moreover, there was a significant interaction between the two (t ratio = -2.24, [Formula: see text]- 1.244, 95% CI 0.15-2.33, p = 0.02), such that the BMI of children born to mothers with both GDM and preeclampsia showed consistent increases over time. CONCLUSIONS: GDM and preeclampsia could be used as a marker for childhood obesity risk and the identification of a high-risk group, providing potential early intervention. These findings highlight the importance of managing obstetric complications, as an effective method of child obesity prevention.