Pathogen protein modularity enables elaborate mimicry of a host phosphatase.

Pathogens produce diverse effector proteins to manipulate host cellular processes. However, how functional diversity is generated in an effector repertoire is poorly understood. Many effectors in the devastating plant pathogen Phytophthora contain tandem repeats of the "(L)WY" motif, which are structurally conserved but variable in sequences. Here, we discovered a functional module formed by a specific (L)WY-LWY combination in multiple Phytophthora effectors, which efficiently recruits the serine/threonine protein phosphatase 2A (PP2A) core enzyme in plant hosts. Crystal structure of an effector-PP2A complex shows that the (L)WY-LWY module enables hijacking of the host PP2A core enzyme to form functional holoenzymes. While sharing the PP2A-interacting module at the amino terminus, these effectors possess divergent C-terminal LWY units and regulate distinct sets of phosphoproteins in the host. Our results highlight the appropriation of an essential host phosphatase through molecular mimicry by pathogens and diversification promoted by protein modularity in an effector repertoire.

Exploring the diverse clinical and variant spectrum of CEP78-associated syndrome: Novel pathogenic variants identified in a case series.

Dual sensory impairment, commonly referred to as combined hearing and vision loss, can stem from a diverse spectrum of conditions, each presenting with its unique set of clinical characteristics. Our understanding of dual sensory impairment has expanded significantly in the past decade, broadening the scope of genetic differential diagnoses, including genes such as CEP250, ARSG, TUBB4B, CEP78, and ABHD12. A case series including three patients from two families with genetically diagnosed CEP78-associated cone-rod dystrophy was identified. We collected and reviewed their clinical records, imaging data, and genetic testing results. In addition, a comprehensive literature review was conducted on the phenotype and the genetic testing modality employed in all published CEP78 cases through a PubMed search using the keyword "CEP78." A retinal dystrophy panel detected a novel homozygous CEP78 pathogenic variant (c.1447C>T, p.Arg483*) in siblings-Cases 1 and 2-from Family 1. Both teenagers have a clinical diagnosis of cone-rod dystrophy with presumed normal hearing. Case 3 from Family 2, diagnosed with cone-rod dystrophy and early-onset hearing loss, was found to carry a CEP78 pathogenic variant (c.1206-2A>C) and a likely pathogenic variant (c.856_857del, p.Leu286Glyfs*12) also through panel-based genetic testing. Intriguingly, neither of these variants was reported in an affected sibling's clinical whole-exome sequencing (WES) report when performed in 2015. A review of CEP78-related literature unveiled that the initial report linking CEP78 to cone-rod dystrophy and hearing loss was published in September 2016. Any pathogenic variant found in CEP78 before 2016 would have been categorized as a "clearly disruptive variant in a gene of uncertain significance (GUS)" and might not have been reported in the WES report. It is important to acknowledge that our understanding of genotype-phenotype associations is undergoing rapid expansion. It is also crucial to recognize that repeat genetic testing may represent a fundamentally different approach, given the technological advancements not only in the coverage of the sequencing but also in the more comprehensive understanding of genotype-phenotype associations. This case series also enriches the existing CEP78 literature by providing phenotypic details of the youngest case of CEP78-associated retinopathy reported in the literature (Case 2), which expands our perspective on the natural history of disease in this disorder.

LECT2 mediates antibacterial immune response induced by Nocardia seriolae infection in the northern snakehead.

Leukocyte-derived chemotaxin-2 (LECT2) is a multifunctional immunoregulator that plays several pivotal roles in the host's defense against pathogens. This study aimed to elucidate the specific functions and mechanisms of LECT2 (CaLECT2) in the northern snakehead (Channa argus) during infections with pathogens such as Nocardia seriolae (N. seriolae). We identified CaLECT2 in the northern snakehead, demonstrating its participation in the immune response to N. seriolae infection. CaLECT2 contains an open reading frame (ORF) of 459 bp, encoding a peptide of 152 amino acids featuring a conserved peptidase M23 domain. The CaLECT2 protein shares 62%-84% identities with proteins from various other fish species. Transcriptional expression analysis revealed that CaLECT2 was constitutively expressed in all examined tissues, with the highest expression observed in the liver. Following intraperitoneal infection with N. seriolae, CaLECT2 transcription increased in the spleen, trunk kidney, and liver. In vivo challenge experiments showed that injecting recombinant CaLECT2 (rCaLECT2) could protect the snakehead against N. seriolae infection by reducing bacterial load, enhancing serum antibacterial activity and antioxidant capacity, and minimizing tissue damage. Moreover, in vitro analysis indicated that rCaLECT2 significantly enhanced the migration, respiratory burst, and microbicidal activity of the head kidney-derived phagocytes. These findings provide new insights into the role of LECT2 in the antibacterial immunity of fish.

Polyketides with α-glucosidase inhibitory and neuroprotective activities from Aspergillus versicolor associated with Pedicularis sylvatica.

Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC50 value of 25.57 µM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.

Ultra-mechanosensitive Chloride Ion Transport through Bioinspired High-Density Elastomeric Nanochannels.

Mechanosensitive ion channels play crucial roles in physiological activities, where small mechanical stimuli induce the membrane tension, trigger the ion channels' deformation, and are further transformed into significant electrochemical signals. Artificial ion channels with stiff moduli have been developed to mimic mechanosensory behaviors, exhibiting an electrochemical response by the high-pressure-induced flow. However, fabricating flexible mechanosensitive channels capable of regulating specific ion transporting upon dramatic deformation has remained a challenge. Here, we demonstrate bioinspired high-density elastomeric channels self-assembled by polyisoprene-b-poly4-vinylpyridine, which exhibit ultra-mechanosensitive chloride ion transport resulting from nanochannel deformation. The PI-formed continuous elastic matrix can transmit external forces into internal tensions, while P4VP forms transmembrane chloride channels that undergo dramatic deformation and respond to mechanical stimuli. The integrated and flexible chloride channels present a dramatic and stable electrochemical signal toward a low pressure of 0.2 mbar. This research first demonstrates the artificial mechanosensory chloride channels, which could provide a promising avenue for designing flexible and responsive channel systems.

Amphiphilic HZSM-5 for Cyclopentene Hydration at the Liquid-Liquid Interface in Pickering Emulsion.

Zeolite is considered an ideal catalyst for olefin hydration due to its high specific surface area and abundant acid sites. However, the immiscibility of the water-oil two phases in olefin hydration limits mass transfer, and the side reaction of etherification occurs acutely, resulting in a low yield of alcohol. Thus, water-oil amphiphilic HZSM-5 was prepared by sulfonating silanized zeolite. The successful introduction of organic and sulfonic acid groups is demonstrated by FT-IR, TG, and water contact angles. Amphiphilic HZSM-5 can stabilize the Pickering emulsion and catalyze cyclopentene hydration at the phase interface. In addition, NH3-TPD and Py-IR show that the amount of strong BroÌ·nsted acid sites of zeolites increases significantly after sulfonation. This facilitates the rate-determining step of cyclopentene activation by H+ to form carbocation. Moreover, the nucleophilic side reactions are inhibited by a high concentration of H+. Finally, under the optimized reaction condition, the conversion of cyclopentene can achieve 5.066% with a selectivity of 85.37% to cyclopentanol, which almost reaches the reaction equilibrium.

Clinical characteristics of patients with prenatal hydronephrosis in early postnatal period: a single center retrospective study.

BACKGROUND: The study aims to investigate the clinical characteristics of early postnatal period in children with prenatal hydronephrosis (HN) in our single center for 8 years. STUDY DESIGN: The clinical data of 1137 children with prenatal HN from 2012 to 2020 were retrospectively analyzed in our center. Variables of our study mainly included different malformations and urinary tract dilation (UTD) classification, and main outcomes were recurrent hospitalization, urinary tract infection (UTI), jaundice, and surgery. RESULTS: Among the 1137 children with prenatal HN in our center, 188 cases (16.5%) were followed-up in early postnatal period, and 110 cases (58.5%) were found malformations. The incidence of recurrent hospitalization (29.8%) and UTI (72.5%) were higher in malformation, but the incidence of jaundice (46.2%) was higher in non-malformation(P < 0.001). Furthermore, UTI and jaundice were higher in vesicoureteral reflux (VUR) than those in uretero-pelvic junction obstruction (UPJO) (P < 0.05). Meanwhile, Children with UTD P2 and UTD P3 were prone to recurrent UTI, but UTD P0 was prone to jaundice (P < 0.001). In addition, 30 cases (16.0%) of surgery were all with malformations, and the surgical rates of UTD P2 and UTD P3 were higher than those of UTD P0 and UTD P1 (P < 0.001). Lastly, we concluded that the first follow-up should be less than 7 days, the first assessment should be 2 months, and the follow up should be at least once every 3 months. CONCLUSION: Children with prenatal HN have been found many malformations in early postnatal period, and with high-grade UTD were more prone to recurrent UTI, even to surgery. So, prenatal HN with malformations and high-grade UTD should be followed up in early postnatal period regularly.

Momentum contrast transformer for COVID-19 diagnosis with knowledge distillation.

Intelligent diagnosis has been widely studied in diagnosing novel corona virus disease (COVID-19). Existing deep models typically do not make full use of the global features such as large areas of ground glass opacities, and the local features such as local bronchiolectasis from the COVID-19 chest CT images, leading to unsatisfying recognition accuracy. To address this challenge, this paper proposes a novel method to diagnose COVID-19 using momentum contrast and knowledge distillation, termed MCT-KD. Our method takes advantage of Vision Transformer to design a momentum contrastive learning task to effectively extract global features from COVID-19 chest CT images. Moreover, in transfer and fine-tuning process, we integrate the locality of convolution into Vision Transformer via special knowledge distillation. These strategies enable the final Vision Transformer simultaneously focuses on global and local features from COVID-19 chest CT images. In addition, momentum contrastive learning is self-supervised learning, solving the problem that Vision Transformer is challenging to train on small datasets. Extensive experiments confirm the effectiveness of the proposed MCT-KD. In particular, our MCT-KD is able to achieve 87.43% and 96.94% accuracy on two publicly available datasets, respectively.

Tricrilactones A-H, Potent Antiosteoporosis Macrolides with Distinctive Ring Skeletons from Trichocladium crispatum, an Alpine Moss-Associated Fungus.

Tricrilactones A-H (1-8), a new family of oligomeric 10-membered macrolides featuring collectively five unique ring skeletons, were isolated from a hitherto unexplored fungus, Trichocladium crispatum. Compounds 1 and 7 contain two unconventional bridged (aza)tricyclic core skeletons, 2, 3, 5, and 6 share an undescribed tetracyclic 9/5/6/6 ring system, 4 bears an uncommon 9/5/6/10/3-fused pentacyclic architecture, and 8 is a dimer bridged by an unexpected C-C linkage. Their structures, including absolute configurations, were elucidated by spectroscopic analysis, quantum chemical calculations, and X-ray diffraction analysis. Importantly, the absolute configuration of the highly flexible side chain of 1 was resolved by the asymmetric synthesis of its four stereoisomers. The intermediate-trapping and isotope labeling experiments facilitated the proposal of the biosynthetic pathway for these macrolides. In addition, their antiosteoporosis effects were evaluated in vivo (zebrafish).

One Porphyrin Per Chain Self-Assembled Helical Ion-Exchange Channels for Ultrahigh Osmotic Energy Conversion.

Ion-exchange membranes (IEMs) convert osmotic energy into electricity when embedded in a reverse electrodialysis cell. IEMs with both high permselectivity and ionic conductivity are highly needed to increase the energy conversion efficiency. The ionic conductivity can be improved by increasing the content of immobile charge carriers, but it is always accompanied by undesirable permselectivity decrease due to excess swelling. Until now, breaking the permselectivity-conductivity tradeoff still has remained a challenge. Here, we demonstrate a membrane with the least ion-exchange capacity (∼10-2 mequiv g-1), generating an ultrahigh power density of 19.3 W m-2 at a 50-fold concentration ratio. The membrane is made of a porphyrin-core four-star block copolymer (p-BCP), forming the high-density helical porphyrin channels (∼1011 cm-2) under the synergistic effect of BCP self-assembly and porphyrin π-π stacking. The porphyrin channel shows high Cl- selectivity and high conductivity, benefiting high-performance osmotic energy conversion. This economic and facile membrane design strategy provides a promising approach to developing a new generation of IEMs.

Subsequent fractures after vertebroplasty in osteoporotic vertebral fractures: a meta-analysis.

Percutaneous vertebroplasty (VP) provides substantial benefit to patients with painful osteoporotic vertebral compression fractures (OVCF). However, the reoccurrence of vertebral fracture after VP is a major concern. The purpose of this study is to conduct a meta-analysis on the incidence of subsequent fractures after VP in patients with OVCF. PubMed and EMBASE were searched. In addition, we scrutinized the reference list of all relevant articles to supplement the database search. We included original articles reporting on new fracture rates after VP in OVCF patients. Subsequent fracture rates were pooled across studies using a random-effects meta-analysis. Thirty-nine studies with a total of 8047 participants from 12 countries were included in this meta-analysis. Patients' age ranged from 64.2 to 94.6 years (reported by 31 studies). The median follow-up was 21 months (36 studies). Pooled estimate for subsequent fractures after VP was 23.4% (95% CI, 19.8-27.2%; I2 = 93.0%, p < 0.01). New fractures after VP in 54.6% of cases occurred in the vertebral bodies adjacent to the treated vertebra (95% CI, 49.0-60.1%; I2 = 66.0%, p < 0.01). A significant proportion of patients undergoing VP for OVCF experience new fractures after treatment, most of which are developed in the vertebral bodies adjacent to the treated vertebra.

Structural analysis of Phytophthora suppressor of RNA silencing 2 (PSR2) reveals a conserved modular fold contributing to virulence.

Phytophthora are eukaryotic pathogens that cause enormous losses in agriculture and forestry. Each Phytophthora species encodes hundreds of effector proteins that collectively have essential roles in manipulating host cellular processes and facilitating disease development. Here we report the crystal structure of the effector Phytophthora suppressor of RNA silencing 2 (PSR2). PSR2 produced by the soybean pathogen Phytophthora sojae (PsPSR2) consists of seven tandem repeat units, including one W-Y motif and six L-W-Y motifs. Each L-W-Y motif forms a highly conserved fold consisting of five α-helices. Adjacent units are connected through stable, directional linkages between an internal loop at the C terminus of one unit and a hydrophobic pocket at the N terminus of the following unit. This unique concatenation results in an overall stick-like structure of PsPSR2. Genome-wide analyses reveal 293 effectors from five Phytophthora species that have the PsPSR2-like arrangement, that is, containing a W-Y motif as the "start" unit, various numbers of L-W-Y motifs as the "middle" units, and a degenerate L-W-Y as the "end" unit. Residues involved in the interunit interactions show significant conservation, suggesting that these effectors also use the conserved concatenation mechanism. Furthermore, functional analysis demonstrates differential contributions of individual units to the virulence activity of PsPSR2. These findings suggest that the L-W-Y fold is a basic structural and functional module that may serve as a "building block" to accelerate effector evolution in Phytophthora.

Vitelline Membrane Protein 26 Mutagenesis, Using CRISPR/Cas9, Results in Egg Collapse in Plutella xylostella.

Vitelline membrane proteins (VMPs) are the main proteins that form the inner shell (vitelline membrane layer) of insect eggs and are an integral part of egg formation and embryo development. Here, we characterized the molecular structure and expression patterns of the VMP26 gene and analyzed its reproductive functions in diamondback moth, Plutella xylostella (L.), a worldwide migratory pest of cruciferous plants. The PxVMP26 gene was shown to be a single exon gene that contained an open reading frame of 852 base pairs (bp) encoding 283 amino acids. Both qPCR and western blot analyses showed that PxVMP26 was specifically expressed in female adults and was significantly highly expressed in the ovary. Further anatomical analysis indicated that the expression level of PxVMP26 in the ovarian tube with an incomplete yolk was significantly higher than that in the ovarian tube with a complete yolk. CRISPR/Cas9-induced PxVMP26 knockout successfully created two homozygous strains with 8- and 46-bp frameshift mutations. The expression deficiency of the PxVMP26 protein was detected in the mutant strains using immunofluorescence and western blot. No significant difference was found in the number of eggs laid within three days between wild and mutant individuals, but there was a lower egg hatchability. The loss of the PxVMP26 gene changed the mean egg size, damaged the structure of the vitelline membrane, and increased the proportion of abnormal eggs due to water loss, resulting in egg collapse. This first analysis of the roles of the VMP gene in the oocyte formation and embryonic development of P. xylostella, using CRISPR/Cas9 technology, provides a basis for screening new genetic control targets of P. xylostella.

[National Nutrition and Health Systematic Survey for 0-18 years old children in China:study protocol for 6-18 years old children].

OBJECTIVE: To systematically collect basic data on nutrition and health of children aged 6-18 years in China. METHODS: A cross-sectional survey was conducted in 7 regions, including Eastern China, Northern China, Central China, Southern China, Southwestern China, Northwestern China, and Northeastern China. A total of 65 000 children aged 6-18 years were selected from 28 urban and rural survey sites in 14 provinces through multistage stratified random cluster sampling. Through a questionnaire survey, physical examination, laboratory examination, dietary survey, children's information on dietary intake, physical development, bone development, psychological intelligence, physiological development, and physique were collected to evaluate children's nutrition and health status; nutrition and health knowledge, physical activity and lifestyle of children and their parents were investigated. RESULTS: The project has basically completed the field investigation and data entry, and it has measured the physical development indicators of 64 999 children aged 6-18 years in China.64 463 completed the student questionnaire; 62 448 completed the body composition measurement, and 3359 completed the assessment of intellectual development. CONCLUSION: This project brings together the nutrition, epidemiology, child care, mental health experts with the centers for disease control and prevention, and maternal and child health care system in our country. Combining with research institutes and children's hospitals of professional expertise, the project comprehensively collects children's dietary nutrition, growth and development, and health-related data in our country. It would put forward strategies to improve the children's nutrition and health in China and provide the basis for data sharing.

The differences of carotid atherosclerosis among non-OSAHS and OSAHS patients of different severities: a cross-sectional study.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a widely prevalent problem with many complications, such as hypertension and cerebral vascular diseases. Atherosclerosis, whose most severe outcome is ischemic stroke, is reported being affected by OSAHS. The objective of this article is to investigate the differences of carotid atherosclerosis patients with or without OSAHS by a cross-sectional research. MATERIALS AND METHODS: Patients diagnosed with carotid atherosclerosis by ultrasonography were recruited. They were requested to fill the primary screening OSAHS questionnaire. Patients with high tendency of OSAHS underwent polysomnography (PSG) tests into OSAHS group, and patients without OSAHS were into non-OSAHS group. Blood tests and medical history were collected. Carotid atherosclerosis severity was analyzed by carotid artery intima-media thickness (IMT), carotid plaque, blood flow velocity, etc. Differences between the two groups and subgroups were analyzed. RESULTS: A total of 242 carotid atherosclerosis patients were enrolled including 118 non-OSAHS patients (38 males and 80 females) and 124 OSAHS patients (40 mild, 32 moderate, and 52 severe). Significant differences were found in PSV-ICA and EDV-ICA on both sides (p < 0.05) but no significant differences on IMT and velocity of CCV. CA patients with OSAHS were younger than ones without OSAHS. With the severity of OSAHS increasing, the age of CA patients decreased. The more severity of OSAHS, the younger the patients were. There were no significant differences in comparing cholesterol, triglyceride, HDL, LDL, and glucose. CONCLUSION: As far as CIMT, carotid plaque, blood flow velocity, and blood lipid are concerned, the severity of CA is not affected by the severity of OSAHS accordantly. The relationship between OSAHS and CA may not be dose dependent. TRIAL REGISTRATION: This study has been registered on clinical trials (No. NCT03665818).

The reproductive regulation of LPXRFa and its receptor in the hypothalamo-pituitary-gonadal axis of the spotted scat (Scatophagus argus).

Gonadotropin-inhibitory hormone (GnIH) plays a critical role in regulating gonadotropin-releasing hormone (GnRH), gonadotropin hormone (GtH), and steroidogenesis. The Lpxrfa (the piscine ortholog of GnIH) system has been found to regulate fish reproduction. To gain insight into the role of Lpxrfa in the regulation of spotted scat (Scatophagus argus) reproduction, spotted scat Lpxrfa (ssLpxrfa), and its receptor (ssLpxrfa-r) were cloned and analyzed. Tissue distribution and expression patterns at the hypothalamo-pituitary-gonadal axis (HPG axis) of sslpxrfa and sslpxrfa-r mRNA were also investigated during gonadal development of spotted scat. The open reading frame (ORF) of the sslpxrfa was 606 bp encoding 201 amino acids and includes a putative signal peptide and two mature ssLpxrfa peptides with LPXRFamide motif at their C-terminus. The sslpxrfa-r ORF was 1449 bp encoding 482 amino acids and contracted a seven-hydrophobic transmembrane (TM) domain structure. The tissue distribution showe d that the sslpxrfa was highly expressed in hypothalami, gill, and the gonads. In addition, sslpxrfa-r was highly expressed in hypothalami, pituitaries, and the gonads. Quantitative real-time polymerase chain reaction (qPCR) revealed that sslpxrfa had the highest expression in the hypothalami and pituitaries, and the lowest expression in the gonads in stage V. During gonadal development, the expression of sslpxrfa-r was gradually increased in the hypothalami but reduced in the gonads. However, no obvious trend was observed in the pituitaries. The expression of sslpxrfa and sslpxrfa-r decreased significantly after injection with 17ß-estradiol (E2). However, the expression of both sslpxrfa and sslpxrfa-r was not changed after injection with 17α-methyltestosterone(17α-MT) in the hypothalami. In addition, no changes were observed in the expression of fshß and lhß in the pituitaries after injecting ssLpxrfa-1. However, ssLpxrfa-2 could downregulate the expression of sbgnrh and fshß in the hypothalami and pituitaries, respectively. Taken together, these findings suggested that ssLpxrfa may participate in E2 feedback in reproduction and regulate the reproductive axis of spotted scat.

[Effect of nuciferine on gut microbiota and inflammatory response in obese model mice].

The aim of this study was to elucidate the mechanism of nuciferine on alleviating obesity based on modulating gut microbiota, ameliorating chronic inflammation, and improving gut permeability. In this study, the obese model mice were induced by high-fat diet and then randomly divided into model group, and nuciferine group; some other mice of the same week age were fed with normal diet as normal group. In the modeling process, the mice were administered intragastrically(ig) for 12 weeks. In the course of both modeling and treatment, the body weight and food intake of mice in each group were measured weekly. After modeling and treatment, the Lee's index, weight percentage of inguinal subcutaneous fat, and the level of blood lipid in each group were measured. The pathological changes of adipocytes were observed by HE staining to evaluate the efficacy of nuciferine treatment in obese model mice. 16 S rRNA sequencing analysis was conducted to study the changes in diversity and abundance of gut microbiota after nuciferine treatment. Enzyme-linked immunosorbent assay(ELISA) and quantitative Real-time polymerase chain reaction(qPCR) were used to detect the levels of inflammatory factors interleukin-6(IL-6), interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α) and the expression of related genes in adipose tissue of mice in each group, so as to evaluate the effect of nuciferine on chronic inflammation of mice in obese model group. qPCR was used to detect the expression of occludin and tight junction protein 1(ZO-1)gene in colon tissure, so as to evaluate the effect of nuciferine on intestinal permeability of mice in obese group. Nuciferine decreased the body weight of obese mice, Lee's index, weight percentage of inguinal subcutaneous fat(P<0.05), and reduced the volume of adipocytes, decreased the level of total cholesterol(TC), triglyceride(TG), and low density lipoprotein cholesterol(LDL-C)(P<0.05) in serum, improved dysbacteriosis, increased the relative abundance of Alloprevotella, Turicibacter, and Lactobacillus, lowered the relative abundance of Helicobac-ter, decreased the expression of inflammatory cytokines IL-6, IL-1ß, and TNF-α genes in adipose tissue(P<0.01), decreased the levels of inflammatory cytokines IL-6, IL-1ß, and TNF-α in serum(P<0.05), and increased the expression of occludin and ZO-1 genes related to tight junction in colon tissue(P<0.01). Nuciferine could treat obesity through modulating gut microbiota, decreasing gut permeability and ameliorating inflammation.

Antimicrobial peptide CAMA-syn expressed in pulmonary epithelium by recombination adenovirus inhibited the growth of intracellular bacteria.

BACKGROUND: Intracellular bacteria, especially Mycobacterium tuberculosis, are important pathogenic microorganisms that endanger human health. Purified and synthesized cecropin A-magainin 2 (CAMA-syn) can exhibit a higher antibacterial activity and lower cytotoxicity. To enhance such antimicrobial potential, it would be desirable to deliver CAMA-syn expressed in lung epithelial cells by an adenovirus vector using gene therapy. METHODS: A549 cells in vitro and lung epithelial cells in vivo were used to express CAMA-syn by transducing recombinant adenovirus Ad-SPC-CAMA/GFP, and the expression of CAMA-syn was determined by a reverse transcriptase-polymerase reaction (RT-PCR) and immunofluorescence. The antimicrobial activity in cells was investigated by colony-forming rate and growth curve. Forty Kunming mice of a Bacillus Calmette-Guerin (BCG) infection animal model were randomly divided into three groups: adenoviruses delivery of Ad-SPC-CAMA/GFP, Ad-CMV-CAMA/GFP and empty-virus Ad-CMV-GFP. The expression of CAMA-syn in mice was confirmed by RT-PCR and immunofluorescence. After tracheal injection of adenoviral vector for 3 days, lungs from the mouse model were extracted and homogenized for detection of colony-forming efficiency. RESULTS: CAMA-syn expressed in lung epithelial cells A549 conferred antimicrobial activity against a series of bacteria, including Salmonella abortusovis and BCG. The results obtained in vivo showed that the colony-forming rate of Ad-SPC-CAMA/GFP (74.54%) and Ad-CMV-CAMA/GFP (62.31%) transduced into mice was significantly lower than that of the control group. CONCLUSIONS: Lung epithelial-specific expression of antimicrobial peptide CAMA-syn mediated by adenovirus suppressed the growth of intracellular bacteria, providing a promising approach for the control of refractory intracellular infection.

Flexible 3D core-shell nanoforest arrays trimetal electrode for high capacitance supercapacitor.

A supercapacitor electrode with high capacitance is mainly based on the careful design of nanostructures and the intelligent hybridization of custom active materials. Herein, we designed 3D core-shell nanoforest arrays with hierarchical structure which are directly grown on carbon cloth using a two-step bracket-hydrothermal method and electrodeposition process. Due to the advantages of large specific surface area, abundant pores and active sites, the structure of Mo-Co-Ni(nanotube)@Ni-Co(nanosheet) arrays can promote electrolyte penetration and ions diffusion, further improving the electrochemical performance. The 3D core-shell nanoforest arrays electrode shows outstanding electrochemical performance: a superb areal capacitance of 9.81 F cm-2 (1998.0 F g-1) at the current densities of 1 mA cm-2, as well as long cycle stability (after 3000 cycles maintains 85.4% of the highest capacitance value). This work may provide a promising method for design of flexible supercapacitor electrode materials.

Phaeosphaones: Tyrosinase Inhibitory Thiodiketopiperazines from an Endophytic Phaeosphaeria fuckelii.

Phaeosphaeria fuckelii, an endophytic fungus associated with the herbal medicine Phlomis umbrosa, produced four new thiodiketopiperazine alkaloids, phaeosphaones A-D (1-4), featuring an unusual ß-(oxy)thiotryptophan motif, along with four known analogues, phaeosphaone E (5), chetoseminudin B (6), polanrazine B (7), and leptosin D (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. Compounds 4, 6, and 8 were found to display mushroom tyrosinase inhibitory activity with IC50 values of 33.2 ± 0.2, 31.7 ± 0.2, and 28.4 ± 0.2 µM, respectively, more potent than that of the positive control, kojic acid (IC50 = 40.4 ± 0.1 µM). A molecular-docking study disclosed the π-π stacking interaction between the indole moiety of 8 and the His243 residue of tyrosinase.