Associations between UGT1A1, SLCO1B1, SLCO1B3, BLVRA and HMOX1 polymorphisms and susceptibility to neonatal severe hyperbilirubinemia in Chinese Han population.

BACKGROUND: Severe neonatal hyperbilirubinemia could lead to kernicterus and neonatal death. This study aimed to analyze the association between single nucleotide polymorphisms in genes involved in bilirubin metabolism and the incidence of severe hyperbilirubinemia. METHODS: A total of 144 neonates with severe hyperbilirubinemia and 50 neonates without or mild hyperbilirubinemia were enrolled in 3 institutions between 2019 and 2020. Twelve polymorphisms of 5 genes (UGT1A1, SLCO1B1, SLCO1B3, BLVRA, and HMOX1) were analyzed by PCR amplification of genomic DNA. Genotyping was performed using an improved multiplex ligation detection reaction technique based on ligase detection reaction. RESULTS: The frequencies of the A allele in UGT1A1-rs4148323 and the C allele in SLCO1B3-rs2417940 in the severe hyperbilirubinemia group (30.2% and 90.6%, respectively) were significantly higher than those in the controls (30.2% vs.13.0%, 90.6% vs. 78.0%, respectively, both p < 0.05). Haplotype analysis showed the ACG haplotype of UGT1A1 were associated with an increased hyperbilirubinemia risk (OR 3.122, p = 0.001), whereas the GCG haplotype was related to a reduced risk (OR 0.523, p = 0.018). CONCLUSION: The frequencies of the A allele in rs4148323 and the C allele in rs2417940 are highly associated with the incidence of severe hyperbilirubinemia in Chinese Han neonates. TRIAL REGISTRATION: Trial registration number:ChiCTR1800020424; Date of registration:2018-12-29.

Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities.

Clinical application of PD-1 and PD-L1 monoclonal antibodies (mAbs) is hindered by their relatively low response rates and the occurrence of drug resistance. Co-expression of B7-H3 with PD-L1 has been found in various solid tumors, and combination therapies that target both PD-1/PD-L1 and B7-H3 pathways may provide  additional therapeutic benefits. Up to today, however, no bispecific antibodies targeting both PD-1 and B7-H3 have reached the clinical development stage. In this study, we generated a stable B7-H3×PD-L1 bispecific antibody (BsAb) in IgG1-VHH format by coupling a humanized IgG1 mAb against PD-L1 with a humanized camelus variable domain of the heavy-chain of heavy-chain antibody (VHH) against human B7-H3. The BsAb exhibited favorable thermostability, efficient T cell activation, IFN-γ production, and antibody-dependent cell-mediated cytotoxicity (ADCC). In a PBMC humanized A375 xenogeneic tumor model, treatment with BsAb (10 mg/kg, i.p., twice a week for 6 weeks) showed enhanced antitumor activities compared to monotherapies and, to some degree, combination therapies. Our results suggest that targeting both PD-1 and B7-H3 with BsAbs increases their specificities to B7-H3 and PD-L1 double-positive tumors and induces a synergetic effect. We conclude that B7-H3×PD-L1 BsAb is favored over mAbs and possibly combination therapies in treating B7-H3 and PD-L1 double-positive tumors.

Microtiter plate-based chemistry and in situ screening: SuFEx-enabled lead discovery of selective AChE inhibitors.

Sulphur fluoride exchange (SuFEx) is a category of click chemistry that enables covalent linking of modular units through sulphur connective hubs. Here, we reported an efficient synthesis and in situ screening method for building a library of sulphonamides on the picomolar scale by SuFEx reaction between a sulphonyl fluoride (RSO2F) core and primary or secondary amines. This biocompatible SuFEx reaction would allow us to rapidly synthesise sulphonamide molecules, and evaluate their ChE inhibitory activity. Compound T14-A24 was identified as a reversible, competitive, and selective AChE inhibitor (Ki = 22 nM). The drug-like evaluation showed that T14-A24 had benign BBB penetration, remarkable neuroprotective effect, and safe toxicological profile. In vivo behavioural study showed that T14-A24 treatment improved the Aß1 - 42-induced cognitive impairment, significantly prevented the effects of Aß1 - 42 toxicity. Therefore, this SuFEx click reaction can accelerate the discovery of lead compounds.

Integrated analysis of tRNA-derived small RNAs in proliferative human aortic smooth muscle cells.

BACKGROUND: Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to vascular remodeling diseases. Recently, it has been discovered that tRNA-derived small RNAs (tsRNAs), a new type of noncoding RNAs, are related to the proliferation and migration of VSMCs. tsRNAs regulate target gene expression through miRNA-like functions. This study aims to explore the potential of tsRNAs in human aortic smooth muscle cell (HASMC) proliferation. METHODS: High-throughput sequencing was performed to analyze the tsRNA expression profile of proliferative and quiescent HASMCs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the sequence results and subcellular distribution of AS-tDR-001370, AS-tDR-000067, AS-tDR-009512, and AS-tDR-000076. Based on the microRNA-like functions of tsRNAs, we predicted target promoters and mRNAs and constructed tsRNA-promoter and tsRNA-mRNA interaction networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to reveal the function of target genes. EdU incorporation assay, Western blot, and dual-luciferase reporter gene assay were utilized to detect the effects of tsRNAs on HASMC proliferation. RESULTS: Compared with quiescent HASMCs, there were 1838 differentially expressed tsRNAs in proliferative HASMCs, including 887 with increased expression (fold change > 2, p < 0.05) and 951 with decreased expression (fold change < ½, p < 0.05). AS-tDR-001370, AS-tDR-000067, AS-tDR-009512, and AS-tDR-000076 were increased in proliferative HASMCs and were mainly located in the nucleus. Bioinformatics analysis suggested that the four tsRNAs involved a variety of GO terms and pathways related to VSMC proliferation. AS-tDR-000067 promoted HASMC proliferation by suppressing p53 transcription in a promoter-targeted manner. AS-tDR-000076 accelerated HASMC proliferation by attenuating mitofusin 2 (MFN2) levels in a 3'-untranslated region (UTR)-targeted manner. CONCLUSIONS: During HASMC proliferation, the expression levels of many tsRNAs are altered. AS-tDR-000067 and AS-tDR-000076 act as new factors promoting VSMC proliferation.

Fluorosulfate-containing pyrazole heterocycles as selective BuChE inhibitors: structure-activity relationship and biological evaluation for the treatment of Alzheimer's disease.

Novel scaffolds are expected to treat Alzheimer's disease, pyrazole-5-fluorosulfates were found as selective BuChE inhibitors. Compounds K1-K26 were assayed for ChE inhibitory activity, amongst them, compound K3 showed potent BuChE and hBuChE inhibition (IC50 = 0.79 µM and 6.59 µM). SAR analysis showed that 1-, 3-, 4-subtituent and 5-fluorosulfate of pyrazole ring affected BuChE inhibitory activity. Molecular docking showed that the fluorosulfate increased the binding affinity of hBuChE through π-sulphur interaction. Compound K3 was a reversible, mixed and non-competitive BuChE inhibitor (Ki = 0.77 µM) and showed remarkable neuroprotection, safe toxicological profile and BBB penetration. In vivo behavioural study showed that K3 treatment improved the Aß1 - 42-induced cognitive impairment, and significantly prevented the effects of Aß1 - 42 toxicity. Therefore, selective BuChE inhibitor K3 has potential to be further developed as AD therapeutics.

Myelin sheath structure and regeneration in peripheral nerve injury repair.

Observing the structure and regeneration of the myelin sheath in peripheral nerves following injury and during repair would help in understanding the pathogenesis and treatment of neurological diseases caused by an abnormal myelin sheath. In the present study, transmission electron microscopy, immunofluorescence staining, and transcriptome analyses were used to investigate the structure and regeneration of the myelin sheath after end-to-end anastomosis, autologous nerve transplantation, and nerve tube transplantation in a rat model of sciatic nerve injury, with normal optic nerve, oculomotor nerve, sciatic nerve, and Schwann cells used as controls. The results suggested that the double-bilayer was the structural unit that constituted the myelin sheath. The major feature during regeneration was the compaction of the myelin sheath, wherein the distance between the 2 layers of cell membrane in the double-bilayer became shorter and the adjacent double-bilayers tightly closed together and formed the major dense line. The expression level of myelin basic protein was positively correlated with the formation of the major dense line, and the compacted myelin sheath could not be formed without the anchoring of the lipophilin particles to the myelin sheath.

[Characteristic chromatogram and index components content of substance benchmark of Xuanfu Daizhe Decoction].

The methods for determining the characteristic chromatogram and index components content of Xuanfu Daizhe Decoction were established to provide a scientific basis for the quality evaluation of substance benchmarks and preparations. Eighteen batches of Xuanfu Daizhe Decoction were prepared with the decoction pieces of different batches and of the same batch were prepared respectively, and the HPLC characteristic chromatograms of these samples were established. The similarities of the chromatographic fingerprints were analyzed. With liquiritin, glycyrrhizic acid, 6-gingerol, ginsenoside Rg_1, and ginsenoside Re as index components, the high performance liquid chromatography was established for content determination with no more than 70%-130% of the mass average as the limit. The results showed that there were 19 characteristic peaks corresponding to the characteristic chromatograms of 18 batches of Xuanfu Daizhe Decoction, including 8 peaks representing liquiritin, 1,5-O-dicaffeoylqunic acid, ginsenoside Rg_1, ginsenoside Re, 1-O-acetyl britannilactone, ginsenoside Rb_1, glycyrrhizic acid, and 6-gingerol, and the fingerprint similarity was greater than 0.97. The contents of liquiritin, glycyrrhizic acid, 6-gingerol, and ginsenosides Rg_1 + Re in the prepared Xuanfu Daizhe Decoction samples were 0.53%-0.86%, 0.61%-1.2%, 0.023%-0.068%, and 0.33%-0.66%, respectively. Except for several batches, most batches of Xuanfu Daizhe Decoction showed stable contents of index components, with no discrete values. The characteristic chromatograms and index components content characterized the information of Inulae Flos, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens in Xuanfu Daizhe Decoction. This study provides a scientific basis for the further research on the key chemical properties of substance benchmark and preparations of Xuanfu Daizhe Decoction.

Micro/Nanoengineered α-Fe2 O3 Nanoaggregate Conformably Enclosed by Ultrathin N-Doped Carbon Shell for Ultrastable Lithium Storage and Insight into Phase Evolution Mechanism.

The Fe-based transition metal oxides are promising anode candidates for lithium storage considering their high specific capacity, low cost, and environmental compatibility. However, the poor electron/ion conductivity and significant volume stress limit their cycle and rate performances. Furthermore, the phenomena of capacity rise and sudden decay for α-Fe2 O3 have appeared in most reports. Here, a uniform micro/nano α-Fe2 O3 nanoaggregate conformably enclosed in an ultrathin N-doped carbon network (denoted as M/N-α-Fe2 O3 @NC) is designed. The M/N porous balls combine the merits of secondary nanoparticles to shorten the Li+ transportation pathways as well as alleviating volume expansion, and primary microballs to stabilize the electrode/electrolyte interface. Furthermore, the ultrathin carbon shell favors fast electron transfer and protects the electrode from electrolyte corrosion. Therefore, the M/N-α-Fe2 O3 @NC electrode delivers an excellent reversible capacity of 901 mA h g-1 with capacity retention up to 94.0 % after 200 cycles at 0.2 A g-1 . Notably, the capacity rise does not happen during cycling. Moreover, the lithium storage mechanism is elucidated by ex situ XRD and HRTEM experiments. It is verified that the reversible phase transformation of α↔γ occurs during the first cycle, whereas only the α-Fe2 O3 phase is reversibly transformed during subsequent cycles. This study offers a simple and scalable strategy for the practical application of high-performance Fe2 O3 electrodes.

First report of Geotrichum candidum causing postharvest sour rot on kiwifruits in China.

Kiwifruit (Actinidia spp.) has been extensively cultivated (about 165728 hm2 recorded in 2017) and postharvest rot diseases have caused severe losses to the industry in China. In October 2019, fruit (n=60) of cv. Xuxiang (A. deliciosa) were obtained from a farm (120.62°E, 28.92°N) in Pan'an county, Zhejiang province, China. After the fruit were stored at 24 °C and 70% relative humidity (RH) for 10 days, soft lesions (20 to 45 mm in diameter) with sour odor and white mycelium were observed on ~20% of fruits (Fig. 1a). Irregular lesions were produced on the mesocarp were off-white to pale yellow (Fig. 1b). Small pieces (4×4 mm) from the lesion margins were excised, surface disinfested in 70% ethanol for 1 min and 10% NaOCl for 5 min, washed, dried, plated on PDA and incubated at 25°C for 7 days. A total of seven pure fungal colonies were obtained, and included two isolates of Nigrospora sphaerica (Li et al. 2018) and five unknown isolates. The remaining five isolates produced thin, flat, white to cream and feathery (Fig.1c & d) mycelium. Hyphae were hyaline, septate, dichotomously branched and break into chains of subglobose to cylindrical arthrospores (Fig. 1e, f & g). The dimension of arthrospores varies from 4.11 to 12.55 × 2.54 to 5.84 µm (n=100) (Fig. 1h). To identify these isolates to species, the internal transcribed spacer (ITS), 26S rDNA, translation elongation factor-1 alpha regions (TEF-1α) were amplified and sequenced (Ma et al. 2018). Sequence analysis indicated no differences in 26S rDNA and TEF-1α, but the ITS that placed the isolates into two phylogenetic groups. Isolates gx2-2 and gx3-1 representing group one (gx2-1, gx2-2, and gx5-1) and group two (gx3-1 and gx4-1) respectively, were employed for further studies. Based on BLASTn analysis, ITS sequences for gx2-2 (MT946912) and gx3-1(MT946913) isolates had 100% and 98.40% identity respectively, with G. candidum accessions KY103452 and KY103455. Nevertheless, 26S rDNA sequences (MT981194; MT981195) showed 99.82% identity with G. candidum accessions JN974268 and KF112070. Consistently, the TEF-1α (MT981184; MT981185) had 100% identity with G. candidum accession MT346370. Phylogenetic trees were constructed using the Neighbor-Joining method with a dataset of ITS (Fig. 2a) and 26S rDNA sequences (Fig. 2b), respectively. Based on morphology and phylogenetic analysis, the pathogens gx2-2 and gx3-1 were identified as Geotrichum candidum (De Hoog et al. 1986). To determine pathogenicity, healthy and mature kiwis cv. Xuxiang were surface sterilized. Wounded and unwounded fruits were inoculated with each conidial suspension derived from the two isolates (107 conidia/mL, 30 µL for each fruit) and stored at 24 °C under 90% RH. Control fruit were treated with sterile distilled water. Each treatment consisted of 20 fruit was evaluated daily for 10 days and repeated once. The symptom was mimic the naturally infected fruits (Fig.1i, m & n). The pathogen could develop into inner pericarp after 7 days while cv. Jinyan (A. chinensis) was used as host (Fig. 1k & l). However, control group remained disease-free (Fig. 1j, o & p). The fungus could penetrate into fruit peel and produce spores that were visualized by scanning electron microscope (Fig.1q & r). For both isolates, the incidence of wounded fruit were 100%, and the incidence of unwounded fruit was 80%. The fungi were re-isolated from diseased tissues and re-identified as G. candidum based on morphology and sequences analyses. G. candidum causes sour rot on many hosts and similar symptom have been previously reported in other regions(Pennycook et al.1989; Horita et al. 2016; Ma, et al. 2018; Zhang et al. 2018; Khan et al. 2019; Halfeld-Vieira et al. 2020), but this is the first report of G. candidum on kiwifruit in China.

Chondroitin sulfate proteoglycan represses neural stem/progenitor cells migration via PTPσ/α-actinin4 signaling pathway.

Neural stem/progenitor cells (NSPCs) are a promising candidate for the cell-replacement therapy after central nervous system (CNS) injury. However, the short of sufficient NSPCs migration and integration into the lesions is an essential challenge for cell-based therapy after CNS injury due to the disturbance of local environmental homeostasis. Chondroitin sulfate proteoglycan (CSPG) is obviously accumulated at the lesions and destroyed local homeostasis after CNS injury. The previous study has demonstrated that the CSPG is a dominating ingredient inhibiting axonal regrowth of newly born neurons after CNS injury. NSPCs, a strain of special neural subtypes, hold the capacity of leading processes formation to regulate NSPCs migration, which has the same mechanism as axonal regrowth. Hence, it is worth investigating the effect of CSPG on NSPCs migration and its underlying mechanism. Here, different concentration of CSPG was used to evaluate its effect on NSPCs migration. The results showed that the CSPG suppressed NSPCs migration in a dose-dependent manner from 10 to 80 µg/mL with phase-contrast microscopy after 24 hours. Meanwhile, transwell assays were performed to certify the above results. Our data indicated that the 40 µg/mL CSPG obviously suppressed NSPCs migration via decreasing filopodia formation using immunofluorescence staining. Furthermore, data indicated that the 40 µg/mL CSPG upregulated protein tyrosine phosphatase receptor σ (PTPσ) expression and decreased α-actinin4 (ACTN4) expression through immunofluorescence, reverse transcription polymerase chain reaction, and Western blot assays. While the inhibitory effect was attenuated using PTPσ-specific small interfering RNA. In addition, data demonstrated that the 40 µg/mL CSPG facilitated NSPCs differentiation into glial fibrillary acidic protein-positive cells and inhibited NSPCs directing into MAP2- and MBP-positive cells. Collectively, these data demonstrated that the CSPG suppressed NSPCs migration through PTPσ/ACTN4 signaling pathway. Meanwhile, CSPG facilitated NSPCs differentiation into astrocytes and inhibited NSPCs directing into neurons and oligodendrocytes.

Immunomodulatory Biscembranoids and Assignment of Their Relative and Absolute Configurations: Data Set Modulation in the Density Functional Theory/Nuclear Magnetic Resonance Approach.

Five new biscembranoids, bistrochelides A-E (3-7), were isolated together with glaucumolides A (1) and B (2) from the soft coral Sarcophyton trocheliophorum. Their structures and absolute configurations were determined by spectroscopic methods, X-ray crystal diffraction, and DFT/NMR (density functional theory/nuclear magnetic resonance) and TDDFT/ECD (time-dependent density functional theory/electronic circular dichroism) calculations. A new approach is introduced to determine the relative configuration of a stereocenter through the dynamic evaluation of the mean absolute errors (MAEs) between the investigated diastereoisomers, moving from an "extended" to a more diagnostic "restricted" set of atoms. This research leads to the structure revision of glaucumolides A and B. In in vitro immunomodulatory screening, compounds 1 and 4 significantly induced the proliferation of CD3+ T cells, while compounds 1 and 5 significantly increased the CD4+/CD8+ ratio at 3 µM.

3D Hierarchical Microballs Constructed by Intertwined MnO@N-doped Carbon Nanofibers towards Superior Lithium-Storage Properties.

MnO is a promising high-capacity anode material for lithium-ion batteries (LIBs), but pristine material suffers short cycle life and poor rate capability, thus hindering the practical application. In this work, a new type of porous MnO microballs stringed with N-doped porous carbon (3DHB-MnO@NC) with a well-connected hierarchical three-dimensional network structure was prepared by the facile self-template method. The 3DHB-MnO@NC electrode can effectively promote the ion/electron transfer and buffer the large volume change of electrode during the electrochemical reaction. As the anode for LIBs, the 3DHB-MnO@NC possesses outstanding cycling performance (1247.7 mA h g-1 after 90 cycles at 200 mA g-1 ) and good rate capabilities (949.6 mA h g-1 after 450 cycles at 1000 mA g-1 ). The facile self-template method of the prepared 3DHB-MnO@NC composite paves a new way for practical applications of MnO in high performance LIBs.

Feasibility of free-breathing dynamic contrast-enhanced MRI of gastric cancer using a golden-angle radial stack-of-stars VIBE sequence: comparison with the conventional contrast-enhanced breath-hold 3D VIBE sequence.

OBJECTIVES: To investigate the feasibility and diagnostic value of free-breathing, radial, stack-of-stars three-dimensional (3D) gradient echo (GRE) sequence ("golden angle") on dynamic contrast-enhanced (DCE) MRI of gastric cancer. METHODS: Forty-three gastric cancer patients were divided into cooperative and uncooperative groups. Respiratory fluctuation was observed using an abdominal respiratory gating sensor. Those who breath-held for more than 15 s were placed in the cooperative group and the remainder in the uncooperative group. The 3-T MRI scanning protocol included 3D GRE and conventional breath-hold VIBE (volume-interpolated breath-hold examination) sequences, comparing images quantitatively and qualitatively. DCE-MRI parameters from VIBE images of normal gastric wall and malignant lesions were compared. RESULTS: For uncooperative patients, 3D GRE scored higher qualitatively, and had higher SNRs (signal-to-noise ratios) and CNRs (contrast-to-noise ratios) than conventional VIBE quantitatively. Though 3D GRE images scored lower in qualitative parameters compared with conventional VIBE for cooperative patients, it provided images with fewer artefacts. DCE parameters differed significantly between normal gastric wall and lesions, with higher Ve (extracellular volume) and lower Kep (reflux constant) in gastric cancer. CONCLUSIONS: The free-breathing, golden-angle, radial stack-of-stars 3D GRE technique is feasible for DCE-MRI of gastric cancer. Dynamic enhanced images can be used for quantitative analysis of this malignancy. KEY POINTS: • Golden-angle radial stack-of-stars VIBE aids gastric cancer MRI diagnosis. • The 3D GRE technique is suitable for patients unable to suspend respiration. • Method scored higher in the qualitative evaluation for uncooperative patients. • The technique produced images with fewer artefacts than conventional VIBE sequence. • Dynamic enhanced images can be used for quantitative analysis of gastric cancer.

Development of an HSV-1 neutralization test with a glycoprotein D specific antibody for measurement of neutralizing antibody titer in human sera.

BACKGROUND: Investigating the neutralizing antibody (NAb) titer against HSV-1 is essential for monitoring the immune protection against HSV-1 in susceptible populations, which would facilitate the development of vaccines against herpes infection and improvement of HSV-1 based oncolytic virotherapy. RESULTS: In this study, we have developed a neutralization test based on the enzyme-linked immunospot assay (ELISPOT-NT) to determine the neutralizing antibody titer against HSV-1 in human serum samples. This optimized assay employed a monoclonal antibody specifically recognizing glycoprotein D to detect the HSV-1 infected cells. With this test, the neutralizing antibody titer against HSV-1 could be determined within one day by automated interpretation of the counts of cell spots. We observed good correlation in the results obtained from ELISPOT-NT and plaque reduction neutralization test (PRNT) by testing 22 human serum samples representing different titers. Moreover, 269 human serum samples collected from a wide range of age groups were tested, the average neutralizing antibody titer (log2NT50) was 8.3 ± 2.8 and the prevalence of NAbs was 83.6 % in this cohort, it also revealed that the average neutralizing antibody titer in different groups increased with the age, and no significant difference in neutralizing antibody titers was observed between males and females. CONCLUSIONS: These results prove that this novel assay would serve as an accurate and simple assay for the assessment of the neutralizing antibody titers against HSV-1 in large cohorts.

EphB2 contributes to human naive B-cell activation and is regulated by miR-185.

EphB2 is an important member of the receptor tyrosine kinases. Recently, EphB2 was shown to facilitate T-cell migration and monocyte activation. However, the effects of EphB2 on B cells remain unknown. In this study, the expression of EphB2 on B cells was tested by Western blot, and the roles of EphB2 in B-cell proliferation, cytokine secretion, and immunoglobulin (Ig) production were evaluated using EphB2 siRNA interference in human B cells from healthy volunteers. Our study revealed that EphB2 was distributed on naive B cells and was up-regulated on activated B cells. Moreover, B-cell proliferation (decreased by 22%, P<0.05), TNF-α secretion (decreased by 40%, P<0.01) and IgG production (decreased by 26%, P < 0.05) were depressed concordantly with the down-regulated EphB2 expression. Subsequently, we screened microRNAs that could regulate EphB2 expression in B cells, and discovered that miR-185 directly targeted to EphB2 mRNA and suppressed its expression. Furthermore, miR-185 overexpression inhibited B-cell activation, and the inhibitor of miR-185 enhanced B-cell activation. Moreover, abatement of EphB2 through miR-185 mimics or EphB2 siRNA attenuated the activation of Src-p65 and Notch1 signaling pathways in human B cells. Our study first suggested that EphB2 was involved in human naive B cell activation through Src-p65 and Notch1 signaling pathways and could be regulated by miR-185.

A plum-pudding like mesoporous SiO2/flake graphite nanocomposite with superior rate performance for LIB anode materials.

A novel kind of plum-pudding like mesoporous SiO2 nanospheres (MSNs) and flake graphite (FG) nanocomposite (pp-MSNs/FG) was designed and fabricated via a facile and cost-effective hydrothermal method. Transmission electron microscopy (TEM) analysis showed that most of the MSNs were well anchored on FG. This special architecture has multiple advantages, including FG that offers a conductive framework and hinders the volume expansion effect. Moreover, the porous structure of MSNs could provide more available lithium storage sites and extra free space to accommodate the mechanical strain caused by the volume change during the repeated reversible reaction between Li(+) and active materials. Due to the synergetic effects of its unique plum-pudding structure, the obtained pp-MSNs/FG nanocomposite exhibited a decent reversible capacity of 702 mA h g(-1) (based on the weight of MSNs in the electrode material) after 100 cycles with high Coulombic efficiency above 99% under 100 mA g(-1) and a charge capacity of 239.6 mA h g(-1) could be obtained even under 5000 mA g(-1). Their high rate performance is among the best-reported performances of SiO2-based anode materials.

Fabrication of functionalized polysulfide reservoirs from large graphene sheets to improve the electrochemical performance of lithium-sulfur batteries.

The effect of graphene lateral size on the electrochemical performance of lithium-sulfur (Li-S) batteries is often ignored. In this study, the thermally exfoliated large lateral-sized graphene (denoted LTG) was employed as the conductive matrix to support sulfur, and its performance was then compared with that of a smaller lateral-sized graphene (denoted STG) for Li-S batteries. The results showed that the LTG-S composite exhibited much higher capacity retention (53%) versus the STG-S (29%) and better rate capabilities. Because they were both identical in morphology, in terms of sulfur content and sulfur distribution, the improved properties probably resulted from the potential prevention of polysulfide diffusion upon cycling due to the larger graphene-based network and higher aspect ratio of the LTG matrix, referred as better polysulfide reservoirs. To further improve the cell performance, a reduced graphene oxide-coated carbon fiber paper (RCF) was inserted between the LTG-S cathode and the separator by a simple drop-coat method, which provided an increased conductive surface area for polysulfides to be oxidized/reduced and buffered volume expansion. As expected, the discharge capacities of 1143 and 622 mA h g(-1) at first use and after 100th cycles were obtained with an average Coulombic efficiency of 99.7%, which were higher than 847 and 455 mA h g(-1) for the cathode without the RCF, respectively. This study highlights the significance of large graphene sheets and interlayers on the inhibition of polysulfide diffusion and offers a new way to solve the problems of Li-S batteries.

Deliberate self-harm among pediatric psychiatric inpatients in China: A single-center retrospective study.

BACKGROUND: For children and adolescents, deliberate self-harm (DSH) is becoming a mental health problem of concern. Despite several studies on the prevalence and factors of DSH in the world, there is little information on DSH among children and adolescents in China. This study explores the prevalence, types, associated risk factors and tendency of DSH in pediatric psychiatric inpatients in China. AIM: To understand the situation of DSH among hospitalized children and adolescents and its related factors. METHODS: In this study, we retrospectively studied 1414 hospitalized children and adolescents with mental illness at Xiamen Mental Health Center from 2014 to 2019, extracted the demographic and clinical data of all patients, and analyzed clinical risk factors of DSH. RESULTS: A total of 239 (16.90%) patients engaged in at least one type of DSH in our study. Cutting (n = 115, 48.12%) was the most common type of DSH. Females (n = 171, 71.55%) were more likely to engage in DSH than males (n = 68, 28.45%). DSH was positively associated with depressive disorders [OR = 3.845 (2.196-6.732); P < 0.01], female [OR = 2.536 (1.815-3.542); P < 0.01], parental marital status [OR = 5.387 (2.254-12.875); P < 0.01] and negative family history of psychiatric illness [OR = 7.767 (2.952-20.433); P < 0.01], but not with occupation, substance use and history of physical abuse. CONCLUSION: Our findings suggest that for patients with depression, females, an abnormal marriage of parents, and no history of mental illness, attention should be paid to the occurrence of DSH.

TNF-α-secreting B cells contribute to myocardial fibrosis in dilated cardiomyopathy.

PURPOSE: Excessive inflammation responses mediated by CD4(+) T cells contributes to myocardial fibrosis in dilated cardiomyopathy (DCM) resulting from viral myocarditis. Recently, some scholars discovered that B cells harbored an abnormal pro-inflammatory capacity besides the production of autoantibodies. Thus, we aimed to explore whether and which type of B cells act on myocardial fibrosis in DCM. METHODS: A total of 56 newly hospitalized DCM patients were studied, and among these, 17 patients accepted the gadolinium enhanced cardiovascular magnetic resonance imaging (MRI) for myocardial fibrosis evaluations. RESULTS: B cell functions including the frequency and proliferation were significantly elevated in DCM patients. After screening the important cytokines including IL-1ß, IL-6, IL-10, IL-17, TNF-α and TGF-ß produced in these B cells by flow cytometry, we found that only the TNF-α-secreting B cells were obviously increased. Furthermore, the TNF-α protein secretion and mRNA levels were also enhanced in LPS-stimulated B cell isolated from DCM patients. In addition, 10 patients (59%) with increased TNF-α-secreting B cells showed late enhancement and boosted serum procollagen type III compared with the other 7 patients (41%) whose enhancement could not be detected. Moreover, the frequencies of TNF-α-secreting B cells were negatively correlated with LVEF and positively correlated with LVEDD, NT-proBNP and procollagen type III in all of the DCM patients. CONCLUSIONS: Our study firstly suggested that TNF-α-secreting B cells were involved in myocardial fibrosis, which revealed the new pathogenic mechanism of B cells in DCM, and therapeutic targets against these cells might be valuable.

Cardiac fibroblasts recruit Th17 cells infiltration into myocardium by secreting CCL20 in CVB3-induced acute viral myocarditis.

AIMS: Th17 cells contributed to myocardial inflammatory injury in acute viral myocarditis (AVMC), and the migration of these cells were mainly mediated by CCL20-secreting inflammatory cells. However, whether and how the resident cells such as cardiomyocytes and cardiac fibroblasts could mediate Th17 cell migration into the heart remains unclear in AVMC. METHODS: The effect of CCL20 on the dynamic alterations of intracardiac Th17 cells and disease severity were investigated through the neutralization of CCL20 in AVMC mice. The key cells releasing CCL20 in the heart and the effects of CCL20-secreting cells on Th17 cell arrest, migration and differentiation were detected in vitro. RESULTS: Neutralization of CCL20 efficiently repressed the myocardial inflammation along with the reduction of Th17 cell infiltrations in the course of AVMC. In vitro, after stimulations of TNF-α, IL-1ß and IL-17, cardiac fibroblasts rather than cardiomyocytes could be dominantly induced for CCL20 production. CCL20-secreting cardiac fibroblasts boosted Th17 cell arrest on endothelium, and induce Th17 cell migration. However, CCL20 produced by cardiac fibroblasts had no effect on Th17 cell differentiation and IL-17 production. CONCLUSIONS: It firstly suggested that cardiac fibroblasts could recruit Th17 cells infiltration into myocardium by secreting CCL20 in AVMC.