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Environmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO2 air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.

Stress variation induced bandgap tuning and surface wettability switching of spinel nickel ferrite (NiFe2O4, NFO) films were demonstrated and directly driven by phase transition via a post-annealing process. Firstly, the as-deposited NFO films showed hydrophilic surface with water contact angle (CA) value of 80 ± 1°. After post-annealing with designed temperatures ranged from 400 to 700 °C in air ambience for 1 hour, we observed that the crystal structure was clearly improved from amorphous-like/ nanocrystalline to polycrystalline with increasing post-annealing temperature and this phenomenon is attributed to the improved crystallinity combined with relaxation of internal stress. Moreover, super-hydrophilic surface (CA = 14 ± 1°) was occurred due to the remarkable grain structure transition. The surface wettability could be adjusted from hydrophilicity to super-hydrophilicity by controlling grain morphology of NFO films. Simultaneously, the saturation magnetization (Ms) values of NFO films at room temperature increased up to 273 emu/cm3 accompanied with transitions of the phase and grain structure. We also observed an exceptionally tunable bandgap of NFO in the range between 1.78 and 2.72 eV under phase transition driving. Meanwhile, our work demonstrates that direct grain morphology combined with the stress tuning can strongly modulate the optical, surface and magnetic characteristics in multifunctional NFO films.

In this work, a high thermoelectric figure of merit, zT of 1.9 at 740 K is achieved in Ge1−xBixTe crystals through the concurrent of Seebeck coefficient enhancement and thermal conductivity reduction with Bi dopants. The substitution of Bi for Ge not only compensates the superfluous hole carriers in pristine GeTe but also shifts the Fermi level (EF) to an eligible region. Experimentally, with moderate 6–10% Bi dopants, the carrier concentration is drastically decreased from 8.7 × 1020 cm−3 to 3–5 × 1020 cm−3 and the Seebeck coefficient is boosted three times to 75 μVK−1. In the meantime, based on the density functional theory (DFT) calculation, the Fermi level EF starts to intersect with the pudding mold band at L point, where the band effective mass is enhanced. The enhanced Seebeck coefficient effectively compensates the decrease of electrical conductivity and thus successfully maintain the power factor as large as or even superior than that of the pristine GeTe. In addition, the Bi doping significantly reduces both thermal conductivities of carriers and lattices to an extremely low limit of 1.57 W m−1K−1 at 740 K with 10% Bi dopants, which is an about 63% reduction as compared with that of pristine GeTe. The elevated figure of merit observed in Ge1−xBixTe specimens is therefore realized by synergistically optimizing the power factor and downgrading the thermal conductivity of alloying effect and lattice anharmonicity caused by Bi doping.

In this work, a high thermoelectric figure of merit, zT of 1.9 at 740 K is achieved in Ge1−xBixTe crystals through the concurrent of Seebeck coefficient enhancement and thermal conductivity reduction with Bi dopants. The substitution of Bi for Ge not only compensates the superfluous hole carriers in pristine GeTe but also shifts the Fermi level (EF) to an eligible region. Experimentally, with moderate 6–10% Bi dopants, the carrier concentration is drastically decreased from 8.7 × 1020 cm−3 to 3–5 × 1020 cm−3 and the Seebeck coefficient is boosted three times to 75 μVK−1. In the meantime, based on the density functional theory (DFT) calculation, the Fermi level EF starts to intersect with the pudding mold band at L point, where the band effective mass is enhanced. The enhanced Seebeck coefficient effectively compensates the decrease of electrical conductivity and thus successfully maintain the power factor as large as or even superior than that of the pristine GeTe. In addition, the Bi doping significantly reduces both thermal conductivities of carriers and lattices to an extremely low limit of 1.57 W m−1K−1 at 740 K with 10% Bi dopants, which is an about 63% reduction as compared with that of pristine GeTe. The elevated figure of merit observed in Ge1−xBixTe specimens is therefore realized by synergistically optimizing the power factor and downgrading the thermal conductivity of alloying effect and lattice anharmonicity caused by Bi doping.

The mitogenome of Chinese grass shrimp, Palaemonetes sinensis, was determined through Illumina sequencing, and the basic characteristics and gene arrangement were analyzed. The mitogenome of P. sinensis was 15955 bp in length, consisting of 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes and one control region, with tightly packed. 33 of these genes were encoded on the heavy strand, and the remainders encoded on the light strand. The composition of P. sinensis mitogenome presented a strong A + T bias, which account for 66.7%. All PCGs were initiated by a canonical ATN codon, except nad5, which was initiated by GTG. The termination codons of the PCGs were TAA, TAG and T–. The secondary structures of 22 tRNAs of P. sinensis had the typical clover structure, except of trnS1 owing to the lack of dihydroxyuridine (DHU) arm. Gene order comparison of P. sinensis and previously-sequenced Palaemoninae revealed a unique translocation between trnT and trnP in Macrobrachium. The phylogenetic analyses showed that three Exopalaemon species formed a monophyletic group and then clustered with two Palaemon species and P. sinensis successively whereas Macrobrachium clustered with Palaemon capensis in the other clade.

Epizootic rabbit enteropathy (ERE) is reproduced successfully in the present study by feeding rabbits a low-fibre diet, and high-throughput sequencing and quantitative real-time PCR (qPCR) analysis were applied to examine the microbial variations in the stomach, small intestine and caecum. The evenness was disturbed and the richness was decreased in the ERE groups. When the rabbits were suffering from ERE, the abundance of the Firmicutes was decreased in three parts of the digestive tract, whereas the Proteobacteria was increased in the stomach and caecum, the Bacteroidetes and Verrucomicrobia were increased in the small intestine. Correlation analysis showed that the reduced concentrations of TVFA and butyrate in the caeca of the ERE group were attributed to the decreased abundances of genera such as Lactobacillus, Alistipes and other fibrolytic bacteria and butyrate- producing bacteria such as Eubacterium and Faecalibacterium. It is concluded that, in terms of microorganisms, the overgrowth of Bacteroides fragilis, Clostridium perfringen, Enterobacter sakazakii and Akkermansia muciniphila and inhibition of Bifidobacterium spp. and Butyrivibrio fibrisolvens in the stomach, small intestine and caecum resulted in a decrease in butyrate yield, leading to the incidence of ERE, and the probability of developing ERE could be manipulated by adjusting the dietary fibre level.

The large-conductance calcium-activated K+ (BK) channel contains two intracellular tandem Ca2+-sensing RCK domains (RCK1 and RCK2), which tetramerize into a Ca2+ gating ring that regulates channel opening by conformational expansion in response to Ca2+ binding. Interestingly, the gating ring’s intersubunit assembly interface harbors the RCK2 Ca2+-binding site, known as the Ca2+ bowl. The gating ring’s assembly interface is made in part by intersubunit coordination of a Ca2+ ion between the Ca2+ bowl and an RCK1 Asn residue, N449, and by apparent intersubunit electrostatic interactions between E955 in RCK2 and R786 and R790 in the RCK2 of the adjacent subunit. To understand the role of the intersubunit assembly interface in Ca2+ gating, we performed mutational analyses of these putative interacting residues in human BK channels. We found that N449, despite its role in Ca2+ coordination, does not set the channel’s Ca2+ sensitivity, whereas E955 is a determinant of Ca2+ sensitivity, likely through intersubunit electrostatic interactions. Our findings provide evidence that the intersubunit assembly interface contains molecular determinants of Ca2+-sensitivity in BK channels.

Specific drug therapy has been proven to improve functional capacity and slow disease progression in pulmonary arterial hypertension (PAH), regretfully with the data on the risk of respiratory tract infection (RTI) associated with specific drug therapy being limited. Databases of Medline, Embase, Cochrane Library and the ClinicalTrials.gov Website were searched for randomized controlled trials (RCTs) that reported the RTI data of PAH-specific drug therapy in patients. The primacy outcome was assessed by employing a fixed-effects model. Totally, 24 trials involving 6307 patients were included in the analysis. PAH-specific drug therapy was not significantly associated with the increased risk of both RTI (19.4% vs. 21.1% RR 1.02, 95%CI 0.92–1.14, P = 0.69) and serious RTI (4.3% vs. 5.0% RR 0.99, 95%CI 0.77–1.26, P = 0.93) compared to placebo. The results were consistent across the key subgroups. No heterogeneity between the studies (I2 = 35.8% for RTI, and I2 = 0.0% for serious RTI) and no publication bias was identified. In conclusion, no significant increase in RTI had been found in PAH-specific drug therapy when compared with placebo. Whereas, RTI in PAH patients is still worthy of clinical attention.

Gallid alphaherpesvirus 2 (GaHV2) is an oncogenic avian herpesvirus inducing Marek’s disease (MD) and rapid-onset T-cell lymphomas. To reveal molecular events in MD pathogenesis and tumorigenesis, the dynamic splenic transcriptome of GaHV2-infected chickens during early infection and pathogenic phases has been determined utilizing RNA-seq. Based on the significant differentially expressed genes (DEGs), analysis of gene ontology, KEGG pathway and protein-protein interaction network has demonstrated that the molecular events happening during GaHV2 infection are highly relevant to the disease course. In the ‘Cornell Model’ description of MD, innate immune responses and inflammatory responses were established at early cytolytic phase but persisted until lymphoma formation. Humoral immunity in contrast began to play a role firstly in the intestinal system and started at late cytolytic phase. Neurological damage caused by GaHV2 is first seen in early cytolytic phase and is then sustained throughout the following phases over a long time period. During the proliferative phase many pathways associated with transcription and/or translation were significantly enriched, reflecting the cell transformation and lymphoma formation. Our work provides an overall view of host responses to GaHV2 infection and offers a meaningful basis for further studies of MD biology.

The large-conductance calcium-activated K+ (BK) channel contains two intracellular tandem Ca2+-sensing RCK domains (RCK1 and RCK2), which tetramerize into a Ca2+ gating ring that regulates channel opening by conformational expansion in response to Ca2+ binding. Interestingly, the gating ring’s intersubunit assembly interface harbors the RCK2 Ca2+-binding site, known as the Ca2+ bowl. The gating ring’s assembly interface is made in part by intersubunit coordination of a Ca2+ ion between the Ca2+ bowl and an RCK1 Asn residue, N449, and by apparent intersubunit electrostatic interactions between E955 in RCK2 and R786 and R790 in the RCK2 of the adjacent subunit. To understand the role of the intersubunit assembly interface in Ca2+ gating, we performed mutational analyses of these putative interacting residues in human BK channels. We found that N449, despite its role in Ca2+ coordination, does not set the channel’s Ca2+ sensitivity, whereas E955 is a determinant of Ca2+ sensitivity, likely through intersubunit electrostatic interactions. Our findings provide evidence that the intersubunit assembly interface contains molecular determinants of Ca2+-sensitivity in BK channels.

Stress variation induced bandgap tuning and surface wettability switching of spinel nickel ferrite (NiFe2O4, NFO) films were demonstrated and directly driven by phase transition via a post-annealing process. Firstly, the as-deposited NFO films showed hydrophilic surface with water contact angle (CA) value of 80 ± 1°. After post-annealing with designed temperatures ranged from 400 to 700 °C in air ambience for 1 hour, we observed that the crystal structure was clearly improved from amorphous-like/ nanocrystalline to polycrystalline with increasing post-annealing temperature and this phenomenon is attributed to the improved crystallinity combined with relaxation of internal stress. Moreover, super-hydrophilic surface (CA = 14 ± 1°) was occurred due to the remarkable grain structure transition. The surface wettability could be adjusted from hydrophilicity to super-hydrophilicity by controlling grain morphology of NFO films. Simultaneously, the saturation magnetization (Ms) values of NFO films at room temperature increased up to 273 emu/cm3 accompanied with transitions of the phase and grain structure. We also observed an exceptionally tunable bandgap of NFO in the range between 1.78 and 2.72 eV under phase transition driving. Meanwhile, our work demonstrates that direct grain morphology combined with the stress tuning can strongly modulate the optical, surface and magnetic characteristics in multifunctional NFO films.

The energetic particles bombardment can produce large internal stress in the zinc oxide (ZnO) thin film, and it can be used to intentionally modify the surface characteristics of ZnO films. In this article, we observed that the internal stress increased from −1.62 GPa to −0.33 GPa, and the naturally wettability of the textured ZnO nanostructured films changed from hydrophobicity to hydrophilicity. According to analysis of surface chemical states, the naturally controllable wetting behavior can be attributed to hydrocarbon adsorbates on the nanostructured film surface, which is caused by tunable internal stress. On the other hand, the interfacial water molecules near the surface of ZnO nanostructured films have been identified as hydrophobic hydrogen structure by Fourier transform infrared/attenuated total reflection. Moreover, a remarkable near-band-edge emission peak shifting also can be observed in PL spectra due to the transition of internal stress state. Furthermore, our present ZnO nanostructured films also exhibited excellent transparency over 80% with a wise surface wetting switched from hydrophobic to hydrophilic states after exposing in ultraviolet (UV) surroundings. Our work demonstrated that the internal stress of the thin film not only induced natural wettability transition of ZnO nanostructured films, but also in turn affected the surface properties such as surface chemisorption.

Sero-negative rheumatoid arthritis (RA) is a highly heterogeneous disorder with only a few additive loci identified to date. We report a genotypic variability-based genome-wide association study (vGWAS) of six cohorts of sero-negative RA recruited in Europe and the US that were genotyped with the Immunochip. A two-stage approach was used: (1) a mixed model to partition dichotomous phenotypes into an additive component and non-additive residuals on the liability scale and (2) the Levene’s test to assess equality of the residual variances across genotype groups. The vGWAS identified rs2852853 (P = 1.3e-08, DHCR7) and rs62389423 (P = 1.8e-05, near IRF4) in addition to two previously identified loci (HLA-DQB1 and ANKRD55), which were all statistically validated using cross validation. DHCR7 encodes an enzyme important in cutaneous synthesis of vitamin D and DHCR7 mutations are believed to be important for early humans to adapt to Northern Europe where residents have reduced ultraviolet-B exposure and tend to have light skin color. IRF4 is a key locus responsible for skin color, with a vitamin D receptor-binding interval. These vGWAS results together suggest that vitamin D deficiency is potentially causal of sero-negative RA and provide new insights into the pathogenesis of the disorder.

Small molecule metabolites and their allosterically regulated repressors play an important role in many gene expression and metabolic disorder processes. These natural sensors, though valuable as good logic switches, have rarely been employed without transcription machinery in cells. Here, two pairs of repressors, which function in opposite ways, were cloned, purified and used to control DNA replication in rolling circle amplification (RCA) in vitro. By using metabolites and repressors as inputs, RCA signals as outputs, four basic logic modules were constructed successfully. To achieve various logic computations based on these basic modules, we designed series and parallel strategies of circular templates, which can further assemble these repressor modules in an RCA platform to realize twelve two-input Boolean logic gates and a three-input logic gate. The RCA-output and RCA-assembled platform was proved to be easy and flexible for complex logic processes and might have application potential in molecular computing and synthetic biology.

We used a novel asymmetric cleavage analysis method based on rolling circle amplification (RCA) to determine the effects of LNA modification of substrate on the two subunits of R.BbvCI cleavage. We designed two sets of cleavage circular substrates by using two different ligation strategies and analyzed the single strand cleavage efficiency affected by different modification positions both from the cleaved strands and the uncleaved strands. Results showed that the effects of LNA on cleavage rates of modified strands and unmodified strands were both site-dependent. The Nb.BbvCI and Nt.BbvCI were affected by LNA modification in different way. Most of the modification positions showed strong inhibition of both of these two nickases cleavage. However, the modification in T3 position of bottom strand hardly affected both of the two nickases activities. The results suggested an intimated interaction between the two subunits of R.BbvCI and the T3 position in bottom strand might be a less tight position which was hard to be disturbed.

We performed a meta analysis to assess the relationship of FCGRs polymorphisms with the risk of SLE. Thirty-five articles (including up to 5741 cases and 6530 controls) were recruited for meta-analysis. The strongest association was observed between FCGR2B rs1050501 and SLE under the recessive genotypic model of C allele in the overall population (CC vs CT/TT, OR = 1.754, 95%CI: 1.422–2.165, P = 1.61 × 10−7) and in Asian population (CC vs CT/TT, OR = 1.784, 95%CI; 1.408–2.261, P = 1.67 × 10−6). We also found that FCGR3A rs396991 were significant association with the susceptibility to SLE in overall population in recessive model of T allele (TT vs TG/GG, OR = 1.263, 95%CI: 1.123–1.421, P = 9.62 × 10−5). The results also showed that significant association between FCGR2A rs1801274 and SLE under the allelic model in the overall population (OR = 0.879 per A allele, 95%CI: 0.819–0.943, P = 3.31 × 10−4). The meta-analysis indicated that FCGR3B copy number polymorphism NA1·NA2 was modestly associated with SLE in overall population (OR = 0.851 per NA1, 95%CI: 0.772–0.938, P = 1.2 × 10−3). We concluded that FCGR2B rs1050501 C allele and FCGR3A rs396991 T allele might contribute to susceptibility and development of SLE, and were under recessive association model. While, FCGR2A rs1801274 A allele and FCGR3B NA1 were associated with SLE and reduced the risk of SLE.

The yellow peach moth (YPM), Conogethes punctiferalis (Guenée), is a multivoltine insect pest of crops and fruits. Antennal-expressed receptors are important for insects to detect olfactory cues for host finding, mate attraction and oviposition site selection. However, few olfactory related genes were reported in YPM until now. In the present study, we sequenced and characterized the antennal transcriptomes of male and female YPM. In total, 15 putative odorant binding proteins (OBPs), 46 putative odorant receptors (ORs) and 7 putative ionotropic receptors (IRs) were annotated and identified as olfactory-related genes of C. punctiferalis. Further analysis of RT-qPCR revealed that all these olfactory genes are primarily or uniquely expressed in male and female antennae. Among which, 3 OBPs (OBP4, OBP8 and PBP2) and 4 ORs (OR22, OR26, OR44 and OR46) were specially expressed in male antennae, whereas 4 ORs (OR5, OR16, OR25 and OR42) were primarily expressed in female antennae. The predicted protein sequences were compared with homologs in other lepidopteran species and model insects, which showed high sequence homologies between C. punctiferalis and O. furnacalis. Our work allows for further functional studies of pheromone and general odorant detection genes, which might be meaningful targets for pest management.

Dumbbell probe (DP) attracts increasing interests in rolling circle amplification (RCA). A universal DP production method through cleavage-ligation of hairpin was proposed and optimized. The production is characterized by restriction endonuclease (RE)-induced cleavage ends ligation. It has the advantage of phosphorylation-free, splint-free and purification-free. To optimize designing, we found that the position of RE cleavage sequence in the stem and the primer position in the loop affected the formation and amplification of DP obviously. Both sticky and blunt ends cleaved by RE produce DP efficiently. Moreover, we introduced this DP into circle to circle (C2C) RCA based on the same cleavage-ligation principle and acquired high sensitivity. By combining a two-ligation design and the C2C strategy, specificity for detecting let-7 family members was increased extremely. Furthermore, coreaction of different steps facilitated convenient formation and amplification process of DP.

Single-nucleotide polymorphisms (SNPs) represent the most widespread type of genetic variation (approximately 90%) in the human genome, and the demand to overcome such variation has received more attention now than ever before. The capacity to rapidly assess SNPs that correlate with disease predisposition, drug efficacy and drug toxicity is a key step for the development of personalized medicine. In this work, a rapid one-step SNP detection method, real-time loop-mediated isothermal amplification (RT-LAMP), was first applied for CYP2C19 polymorphisms testing. The optimized method was established with specifically designed primers for target amplification by real-time detection in approximately 30 min under isothermal conditions. RT-LAMP amplified few copies of template to produce significant amounts of product and quantitatively detected human DNA with compatible specificity and sensitivity. The success in the establishment of this RT-LAMP protocol for CYP2C19 polymorphism testing is significant for the extension of this technique for the detection of other SNPs, which will further facilitate the development of personalized medicine.

Dry eye is a highly prevalent, chronic and multifactorial disease that compromises quality of life and generates socioeconomic burdens. The pathogenic factors of dry eye disease (DED) include tear secretion abnormalities, tear film instability and ocular surface inflammation. An effective intervention targeting the pathogenic factors is needed to control this disease. Here we applied α-Melanocyte-stimulating hormone (α-MSH) twice a day to the ocular surface of a scopolamine-induced dry eye rat model. The results showed that α-MSH at different doses ameliorated tear secretion, tear film stability and corneal integrity and corrected overexpression of proinflammatory factors, TNF-α, IL-1β and IFN-γ, in ocular surface of the dry eye rats. Moreover, α-MSH, at 10−4 μg/μl, maintained corneal morphology, inhibited apoptosis and restored the number and size of conjunctival goblet cells in the dry eye rats. Mechanistically, α-MSH activated both PKA-CREB and MEK-Erk pathways in the dry eye corneas and conjunctivas; pharmacological blockade of either pathway abolished α-MSH’s protective effects, suggesting that both pathways are necessary for α-MSH’s protection under dry eye condition. The peliotropic protective functions and explicit signaling mechanism of α-MSH warrant translation of the α-MSH-containing eye drop into a novel and effective intervention to DED.

For the novel interpretation of Raman spectrum from molecule at metal surface, the plasmon driven surface catalysis (PDSC) reactions have become an interesting topic in the research field of surface enhanced Raman scattering (SERS). In this work, the selective PDSC reactions of p,p’-dimercaptoazobenzene (DMAB) produced from para-aminothiophenol (PATP) or 4-nitrobenzenethiol (4NBT) were demonstrated in the Ag nanowires dimer-Au film systems. The different SERS spectra collected at individual part and adjacent part of the same nanowire-film system pointed out the importance of the electromagnetic field redistribution induced by image charge on film in this selective surface catalysis, which was confirmed by the simulated electromagnetic simulated electro- magnetic field distributions. Our result indicated this electromagnetic field redistribution induced selective surface catalysis was largely affected by the polarization and wavelength of incident light but slightly by the difference in diameters between two nanowires. Our work provides a further understanding of PDSC reaction in metal nanostructure and could be a deep support for the researches on surface catalysis and surface analysis.

Glutamate excitotoxicity is a common pathology to blinding ischemic retinopathies, such as diabetic retinopathy, glaucoma and central retinal vein or artery occlusion. The development of an effective interventional modality to glutamate excitotoxicity is hence important to preventing blindness. Herein we showed that α-melanocyte-stimulating hormone (α-MSH) time-dependently protected against glutamate-induced cell death and tissue damage in an improved embryonic chicken retinal explant culture system. α-MSH down-regulated microRNA-194 (miR-194) expression during the glutamate excitotoxicity in the retinal explants. Furthermore, pharmacological antagonists to melanocortin 4 receptor (MC4R) and lentivirus-mediated overexpression of pre-miR-194 abrogated the suppressing effects of α-MSH on glutamate-induced activities of caspase 3 or 7, the ultimate enzymes for glutamate-induced cell death. These results suggest that the protective effects of α-MSH may be due to the MC4R mediated-down-regulation of miR-194 during the glutamate-induced excitotoxicity. Finally, α-MSH attenuated cell death and recovered visual functions in glutamate-stimulated post-hatch chick retinas. These results demonstrate the previously undescribed protective effects of α-MSH against glutamate-induced excitotoxic cell death in the cone-dominated retina both in vitro and in vivo and indicate a novel molecular mechanism linking MC4R-mediated signaling to miR-194.

The formation of glial scar impedes the neurogenesis and neural functional recovery following cerebral ischemia. Histamine showed neuroprotection at early stage after cerebral ischemia, however, its long-term effect, especially on glial scar formation, hasn’t been characterized. With various administration regimens constructed for histidine, a precursor of histamine, we found that histidine treatment at a high dose at early stage and a low dose at late stage demonstrated the most remarkable long-term neuroprotection with decreased infarct volume and improved neurological function. Notably, this treatment regimen also robustly reduced the glial scar area and facilitated the astrocyte migration towards the infarct core. In wound-healing assay and transwell test, histamine significantly promoted astrocyte migration. H2 receptor antagonists reversed the promotion of astrocyte migration and the neuroprotection provided by histidine. Moreover, histamine upregulated the GTP-bound small GTPase Rac1, while a Rac1 inhibitor, NSC23766, abrogated the neuroprotection of histidine and its promotion of astrocyte migration. Our data indicated that a dose/stage-dependent histidine treatment, mediated by H2 receptor, promoted astrocyte migration towards the infarct core, which benefited long-term post-cerebral ischemia neurological recovery. Therefore, targeting histaminergic system may be an effective therapeutic strategy for long-term cerebral ischemia injury through its actions on astrocytes.

In this work, the circular dichroisms (CD) of nanorice heterodimers consisting of two parallel arranged nanorices with the same size but different materials are investigated theoretically. Symmetry-breaking is introduced by using different materials and oblique incidence to achieve strong CD at the vicinity of Fano resonance peaks. We demonstrate that all Au-Ag heterodimers exhibit multipolar Fano resonances and strong CD effect. A simple quantitative analysis shows that the structure with larger Fano asymmetry factor has stronger CD. The intensity and peak positions of the CD effect can be flexibly tuned in a large range by changing particle size, shape, the inter-particle distance and surroundings. Furthermore, CD spectra exhibit high sensitivity to ambient medium in visible and near infrared regions. Our results here are beneficial for the design and application of high sensitive CD sensors and other related fields., Comment: 17 pages,9 figures, including supporting information

Given the existence of plenty of river valleys connecting Southeast and East Asia, it is possible that some inland route(s) might have been adopted by the initial settlers to migrate into the interior of East Asia. Here we analyzed mitochondrial DNA (mtDNA) HVS variants of 845 newly collected individuals from 14 Myanmar populations and 5,907 published individuals from 115 populations from Myanmar and its surroundings. Enrichment of basal lineages with the highest genetic diversity in Myanmar suggests that Myanmar was likely one of the differentiation centers of the early modern humans. Intriguingly, some haplogroups were shared merely between Myanmar and southwestern China, hinting certain genetic connection between both regions. Further analyses revealed that such connection was in fact attributed to both recent gene flow and certain ancient dispersals from Myanmar to southwestern China during 25–10 kya, suggesting that, besides the coastal route, the early modern humans also adopted an inland dispersal route to populate the interior of East Asia.

Contemporary Jews retain a genetic imprint from their Near Eastern ancestry, but obtained substantial genetic components from their neighboring populations during their history. Whether they received any genetic contribution from the Far East remains unknown, but frequent communication with the Chinese has been observed since the Silk Road period. To address this issue, mitochondrial DNA (mtDNA) variation from 55,595 Eurasians are analyzed. The existence of some eastern Eurasian haplotypes in eastern Ashkenazi Jews supports an East Asian genetic contribution, likely from Chinese. Further evidence indicates that this connection can be attributed to a gene flow event that occurred less than 1.4 kilo-years ago (kya), which falls within the time frame of the Silk Road scenario and fits well with historical records and archaeological discoveries. This observed genetic contribution from Chinese to Ashkenazi Jews demonstrates that the historical exchange between Ashkenazim and the Far East was not confined to the cultural sphere but also extended to an exchange of genes.