Helical van der Waals crystals with discretized Eshelby twist.

The ability to manipulate the twisting topology of van der Waals structures offers a new degree of freedom through which to tailor their electrical and optical properties. The twist angle strongly affects the electronic states, excitons and phonons of the twisted structures through interlayer coupling, giving rise to exotic optical, electric and spintronic behaviours1-5. In twisted bilayer graphene, at certain twist angles, long-range periodicity associated with moiré patterns introduces flat electronic bands and highly localized electronic states, resulting in Mott insulating behaviour and superconductivity3,4. Theoretical studies suggest that these twist-induced phenomena are common to layered materials such as transition-metal dichalcogenides and black phosphorus6,7. Twisted van der Waals structures are usually created using a transfer-stacking method, but this method cannot be used for materials with relatively strong interlayer binding. Facile bottom-up growth methods could provide an alternative means to create twisted van der Waals structures. Here we demonstrate that the Eshelby twist, which is associated with a screw dislocation (a chiral topological defect), can drive the formation of such structures on scales ranging from the nanoscale to the mesoscale. In the synthesis, axial screw dislocations are first introduced into nanowires growing along the stacking direction, yielding van der Waals nanostructures with continuous twisting in which the total twist rates are defined by the radii of the nanowires. Further radial growth of those twisted nanowires that are attached to the substrate leads to an increase in elastic energy, as the total twist rate is fixed by the substrate. The stored elastic energy can be reduced by accommodating the fixed twist rate in a series of discrete jumps. This yields mesoscale twisting structures consisting of a helical assembly of nanoplates demarcated by atomically sharp interfaces with a range of twist angles. We further show that the twisting topology can be tailored by controlling the radial size of the structure.

Synthetic Placement of Active Sites in MFI Zeolites for Selective Toluene Methylation to para-Xylene.

Brønsted acidic zeolites are ubiquitous catalysts in fuel and chemical production. Broadening the catalytic diversity of a given zeolite requires strategies to manipulate the acid site placement at framework positions within distinct microporous locations. Here, we combine experiment and theory to elucidate how intermolecular interactions between organic structure-directing agents (OSDAs) and framework Al centers influence the placement of H+ sites in distinct void environments of MFI zeolites and demonstrate the catalytic consequences of active site location on kinetically controlled (403 K) toluene methylation to xylene regioisomers. Kinetic measurements, interpreted using mechanism-derived rate expressions and transition state theory, alongside density functional theory (DFT) calculations show that larger intersection environments similarly stabilize all three xylene isomer transition states without altering well-established aromatic substitution patterns (ortho/para/meta ∼ 60%:30%:10%), while smaller channel environments preferentially destabilize transition states that form bulkier ortho- and meta-isomers, thereby resulting in high intrinsic para-xylene selectivity (∼80%). DFT calculations reveal that the flexibility of nonconventional OSDAs (e.g., 1,4-diazabicyclo[2.2.2]octane) to reorient within MFI intersections and their ability to hydrogen-bond to form protonated complexes favor the placement of Al in smaller channel environments compared to conventional quaternary OSDAs (e.g., tetra-n-propylammonium). These molecular-level insights establish a mechanistic link between OSDA structure, active site placement, and transition state stability in MFI zeolites and provide active site design strategies that are orthogonal to crystallite design approaches harnessing complex reaction-diffusion phenomena to enhance regioisomer selectivity in the industrial production of valuable polymer precursors.

Proteomic profiling of aqueous humor-derived exosomes in Vogt-Koyanagi-Harada disease and Behcet's uveitis.

Vogt-Koyanagi-Harada (VKH) disease and Behcet's uveitis (BU) are the two major vision-threatening uveitis entities. This study performed the first label-free quantitative proteomics on aqueous humor-derived exosomes from 84 patients with VKH or BU to determine their potential roles. Sixty-five differentially expressed proteins (DEPs) and 40 DEPs were detected in the VKH and BU groups, respectively. GO and KEGG analysis showed that DEPs were mainly enriched in the complement-related pathways. The complement C1q subcomponent subunit B (C1QB) was identified as a key exosomal protein, and its expression was significantly increased by western blotting in both diseases. Additionally, the integrated analysis based on the published scRNA-seq data showed that C1QB-containing exosomes were mainly produced by mononuclear macrophages in the anterior segment tissue. Overall, our proteomic profiling highlights that complement-related pathways may be actively involved in the pathogenesis of these two diseases. These pathways may also serve as treatment targets for both diseases.

Novel Polystyrene-Binding Nanobody for Enhancing Immunoassays: Insights into Affinity, Immobilization, and Application Potential.

Nanobodies, which represent the next generation of antibodies due to their unique properties, face a significant limitation in their poor physical adsorption on solid supports. In this study, we successfully discovered polystyrene binding nanobodies from a synthetic nanobody library. Notably, bivalent nanobody B2 exhibited high affinity for polystyrene (0.7 nM for ELISA saturation binding analysis and 15.6 nM for isothermal titration calorimetry), displaying a pH-dependent behavior. Remarkably, hydrophobic and electrostatic interactions contribute minimally to the binding process. Molecular modeling provided insights into the interaction between B2 and polystyrene, revealing that the Trp51 residue within the CDR2 loop formed an aromatic H-bond with polystyrene at a distance of 2.74 Å, thus explaining the observed reduction in B2 affinity caused by Trp51 mutations. To explore B2's potential in protein immobilization, we constructed a bispecific nanobody by fusing B2 to an anticarcinoembryonic antigen nanobody 11C12, which cannot be immobilized on polystyrene through passive adsorption. Remarkably, the fusion construct achieved effective immobilization on polystyrene within 5 min by passing the need for periplasmic protein purification despite its low expression level. Moreover, the fusion construct demonstrated excellent linearity in the chemiluminescent enzyme immunoassay. For the first time, this study reports a simplified and seamless platform for the oriented immobilization of nanobody. Importantly, the entire process eliminated the need for protein purification, enabling efficient and rapid immobilization of fusion proteins directly from crude cell extracts, even when the expression level was low. Our developed process dramatically reduced the processing time from 2.5 days to just 5 min.

Electrochemical Synthesis of Selenosulfonates from Diselenides and Sulfonyl Hydrazides.

The electrochemical oxidative radical-radical cross-coupling of sulfonyl hydrazides with diselenides for the synthesis of selenosulfonates was successfully accomplished. The method is applicable to a wide range of aromatic/aliphatic sulfonyl hydrazides and diselenides, providing products in good to excellent yields. Notably, this protocol stands out for its green and sustainable nature, as it does not rely on transition metals and oxidizing agents, and the starting materials are cost-effective and readily available.

Sphingomonas lacusdianchii sp. nov., an attached bacterium inhibited by metabolites from its symbiotic cyanobacterium.

An alpha-proteobacterial strain JXJ CY 53 T was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) collected from Lake Dianchi, China. JXJ CY 53 T was observed to be an aerobic, Gram-stain-negative, oval shaped, and mucus-secreting bacterium. It had C18:1ω7c and C16:0 as the major cellular fatty acids, Q-10 as the predominant ubiquinone, and sphingoglycolipid, diphosphatidylglycerol, phosphatidylcholine, and phosphatidylmethylethanolamine as the polar lipids. The G + C content of DNA was 65.85%. The bacterium had 16S rRNA gene sequence identities of 98.9% and 98.7% with Sphingomonas panni DSM 15761 T and Sphingomonas hankookensis KCTC 22579 T, respectively, while less than 97.4% identities with other members of the genus. Further taxonomic analysis indicated that JXJ CY 53 T represented a new member of Sphingomonas, and the species epithet was proposed as Sphingomonas lacusdianchii sp. nov. (type strain JXJ CY 53 T = KCTC 72813 T = CGMCC 1.17657 T). JXJ CY 53 T promoted the growth of MF-905 by providing bio-available phosphorus and nitrogen, plant hormones, vitamins, and carotenoids. It could modulate the relative abundances of nonculturable bacteria associated with MF-905 and influence the interactions of MF-905 and other bacteria isolated from the cyanobacterium, in addition to microcystin production characteristics. Meanwhile, MF-905 could provide JXJ CY 53 T dissolved organic carbon for growth, and control the growth of JXJ CY 53 T by secreting specific chemicals other than microcystins. Overall, these results suggest that the interactions between Microcystis and its attached bacteria are complex and dynamic, and may influence the growth characteristics of the cyanobacterium. This study provided new ideas to understand the interactions between Microcystis and its attached bacteria. KEY POINTS: • A novel bacterium (JXJCY 53 T) was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) • JXJCY 53 T modulated the growth and microcystin production of MF-905 • MF-905 could control the attached bacteria by specific chemicals other than microcystins (MCs).

PmiREN2.0: from data annotation to functional exploration of plant microRNAs.

Nearly 200 plant genomes have been sequenced over the last two years, and new functions of plant microRNAs (miRNAs) have been revealed. Therefore, timely update of the plant miRNA databases by incorporating miRNAs from the newly sequenced species and functional information is required to provide useful resources for advancing plant miRNA research. Here we report the update of PmiREN2.0 (https://pmiren.com/) with an addition of 19 363 miRNA entries from 91 plants, doubling the amount of data in the original version. Meanwhile, abundant regulatory information centred on miRNAs was added, including predicted upstream transcription factors through binding motifs scanning and elaborate annotation of miRNA targets. As an example, a genome-wide regulatory network centred on miRNAs was constructed for Arabidopsis. Furthermore, phylogenetic trees of conserved miRNA families were built to expand the understanding of miRNA evolution across the plant lineages. These data are helpful to deduce the regulatory relationships concerning miRNA functions in diverse plants. Beside the new data, a suite of design tools was incorporated to facilitate experimental practice. Finally, a forum named 'PmiREN Community' was added for discussion and resource and new discovery sharing. With these upgrades, PmiREN2.0 should serve the community better and accelerate miRNA research in plants.

In Situ Separable Nanovaccines with Stealthy Bioadhesive Capability for Durable Cancer Immunotherapy.

Because of tumor heterogeneity and the immunosuppressive tumor microenvironment, most cancer vaccines typically do not elicit robust antitumor immunological responses in clinical trials. In this paper, we report findings about a bioadhesive nanoparticle (BNP)-based separable cancer vaccine, FeSHK@B-ovalbumin (OVA), to target multi-epitope antigens and exert effective cancer immunotherapy. After the FeSHK@B-OVA "nanorocket" initiates the "satellite-rocket separation" procedure in the acidic tumor microenvironment, the FeSHK@B "launch vehicle" can amplify intracellular oxidative stress persistently. This procedure allows for bioadhesiveness-mediated prolonged drug retention within the tumor tissue and triggers the immunogenic death of tumor cells that transforms the primary tumors into antigen depots, which acts synergistically with the OVA "satellite" to trigger robust antigen-specific antitumor immunity. The cooperation of these two immunostimulants not only efficiently inhibits the primary tumor growth and provokes durable antigen-specific immune activation in vivo but also activates a long-term and robust immune memory effect to resist tumor rechallenge and metastasis. These results highlight the enormous potential of FeSHK@B-OVA to serve as an excellent therapeutic and prophylactic cancer nanovaccine. By leveraging the antigen depots in situ and the synergistic effect among multi-epitope antigens, such a nanovaccine strategy with stealthy bioadhesion may offer a straightforward and efficient approach to developing various cancer vaccines for different types of tumors.

TET2-mediated upregulation of 5-hydroxymethylcytosine in LRRC39 promoter promotes Th1 response in association with downregulated Treg response in Vogt-Koyanagi-Harada disease.

DNA 5-Hydroxymethylcytosine (5-hmC), an oxidative reaction mediated by the ten-eleven translocation (TET) family, has been reported to play an essential role in the progression of auto-inflammatory and autoimmune diseases. By far, little is known about the effect of DNA 5-hmC and the TET family on the development of Vogt-Koyanagi-Harada (VKH) disease. In this study, we discovered that the global DNA 5-hmC level and the TET activity were elevated in association with the up-regulated expression of TET2 at both mRNA and protein levels in CD4+T cells from active VKH patients compared to healthy controls. Integrated analysis of DNA 5-hmC pattern and transcription profile of CD4+ T cells revealed that 6 candidate target genes were involved in the development of VKH disease. The promoter 5-hmC and mRNA levels of leucine rich repeat containing 39 (LRRC39) were verified to be elevated in active VKH patients. Functional experiments showed that TET2 could up-regulate LRRC39 mRNA expression by increasing the promoter 5-hmC level of LRRC39 in CD4+ T cells from active VKH patients. Up-regulated LRRC39 expression could increase the frequencies of IFN-γ+ and IL-17+ CD4+ T cells as well as the secretions of IFN-γ and IL-17 in association with the decreased frequency of CD4+CD25+FOXP3+ regulatory T (Treg) cells and the reduced production of IL-10. Additionally, restoration of LRRC39 rescued TET2-silencing-mediated reduced frequency of IFN-γ+ CD4+ T cells and increased frequency of CD4+CD25+FOXP3+ Treg cells. Collectively, our study reveals a novel axis, the TET2-5-hmC-LRRC39-Th1/Treg responses axis, in the pathogenesis of VKH and provides a potential target for further investigation into the epigenetic therapy of this disease.

Insights into the convergent evolution of fructan biosynthesis in angiosperms from the highly characteristic chicory genome.

Fructans in angiosperms play essential roles in physiological functions and environmental adaptations. As a major source of industrial fructans (especially inulin-type), chicory (Cichorium intybus L.) is a model species for studying fructan biosynthesis. However, the genes underlying this process and their evolutionary history in angiosperms remain elusive. We combined multiple sequencing technologies to assemble and annotate the chicory genome and scan its (epi)genomic features, such as genomic components, DNA methylation, and three-dimensional (3D) structure. We also performed a comparative genomics analysis to uncover the associations between key traits and gene families. We achieved a nearly complete chicory genome assembly and found that continuous bursts of a few highly active retrotransposon families largely shaped the (epi)genomic characteristics. The highly methylated genome with its unique 3D structure potentially influences critical biological processes. Our comprehensive comparative genomics analysis deciphered the genetic basis for the rich sesquiterpene content in chicory and indicated that the fructan-accumulating trait resulted from convergent evolution in angiosperms due to shifts in critical sites of fructan-active enzymes. The highly characterized chicory genome provides insight into Asteraceae evolution and fructan biosynthesis in angiosperms.

Molecular diagnostic yield for Blau syndrome in previously diagnosed juvenile idiopathic arthritis with uveitis or cutaneous lesions.

OBJECTIVE: Diagnostic pitfalls often arise in the community because of potentially misleading similarities between juvenile idiopathic arthritis (JIA) and Blau syndrome, an immune-related disorder caused by NOD2 gene mutations. It remains unclear in which population and to which extent next-generation sequencing techniques can aid in diagnosis. METHODS: We evaluated clinical usefulness of targeted next-generation sequencing in previously diagnosed JIA. Participants were required to have symptoms and signs suspected of Blau syndrome, including at least uveitis or cutaneous lesions in addition to arthritis. Targeted sequencing was conducted on NOD2 gene to detect diagnostic variants classified as pathogenic or likely pathogenic for Blau syndrome. We assessed the molecular diagnostic yield and clinical implications on patient care. RESULTS: Between May 1, 2008, and June 1, 2021, sequencing data were accrued from 123 previously diagnosed JIA (median age: 5 years; female: 62.6%). Targeted NOD2 sequencing yielded a positive molecular diagnosis of Blau syndrome in 21.1% (95% CI, 14.9%-29.2%), encompassing six heterozygous missense mutations classified as pathogenic variants. Among those receiving a molecular diagnosis, changes in clinical management and treatment were considered as having occurred in 38.5%. Nine predictors were identified to be associated with a higher diagnostic yield, providing clinical clues to suspect the possibility of Blau syndrome. CONCLUSION: Among some patients with pediatric-onset arthritis complicated with uveitis or cutaneous lesions, reassessing their diagnosis of JIA may be warranted. Targeted NOD2 sequencing established the molecular diagnosis of Blau syndrome in nearly one fifth of these cases and provided clinically relevant information for patient-care decisions.

HLA-DR genetic polymorphisms and hepatitis B virus mutations affect the risk of hepatocellular carcinoma in Han Chinese population.

BACKGROUND: Human leucocyte antigen (HLA)-DR plays a crucial role in the immune response against hepatitis B virus (HBV). We aimed to investigate the associations of HLA-DR single nucleotide polymorphisms (SNPs) with the generation of hepatocellular carcinoma (HCC)-related HBV mutations. The effects of HLA-DR SNPs and their interactions with HBV mutations on HCC risks were also determined. METHODS: Five HLA-DR SNPs (rs3135363, rs9268644, rs35445101, rs24755213, and rs984778) were genotyped in 792 healthy controls, 586 chronic hepatitis B (CHB) patients, 536 liver cirrhosis (LC) patients, and 1500 HCC patients using quantitative PCR. Sanger sequencing was used to identify the HBV mutations. Logistic regression model was performed to evaluate the association of HLA-DR SNPs with HCC risk and the frequencies of HCC-related HBV mutations. RESULTS: The variant genotypes at rs3135363, rs9268644, rs35445101, rs24755213, and rs984778 were associated with decreased HCC risks. In genotype C HBV-infected subjects, variant genotypes of these SNPs were associated with decreased frequencies of HCC-related HBV mutations such as C1653T, T1674C/G, G1719T, T1753A/C, A1762T/G1764A, A1846T, G1896A, G1899A, and preS deletion. AG genotype at rs3135363, CA genotype at rs9268644, and AG genotype at rs24755213 reduced the generation of T1753A/C and G1896A in genotype B HBV-infected subjects, respectively. In addition, the interactions of rs3135363, rs9268644, rs24755213 with C1653T, T1753A/C, A1846T, and G1896A decreased the risks of HCC. CONCLUSIONS: HLA-DR genetic polymorphisms might predispose the host to immunoselection of HCC-related HBV mutations and affect the HCC risks possibly through interacting with HBV mutations.

Direct Hydroxylarylation of Benzylic Carbons (sp3/sp2/sp) via Radical-Radical Cross-Coupling Powered by Paired Electrolysis.

Diaryl alcohol moieties are widespread in pharmaceuticals. Existing methods for the synthesis of diaryl alcohols require the use of pre-functionalized benzylic alcohols, aromatic aldehydes, or ketones as starting materials. Herein, the first convergent paired electrochemical approach to the direct hydroxylarylation of unactivated benzylic carbons (sp3/sp2/sp) is proposed. This protocol features direct functionalization of unactivated benzylic C(sp3)-H bonds and benzylic sp2/sp-carbons, mild conditions (open air, room temperature), an environmentally friendly procedure (without any external catalyst/mediator/additive), and direct access to sterically hindered alcohols from inexpensive and readily available alkyl/alkenyl/alkynylbenzenes. Mechanistic studies, including divided-cell experiments, isotope labeling, radical trapping, electron paramagnetic resonance, reaction kinetics, and cyclic voltammetry, strongly support the proposed radical-radical cross-coupling between transient ketyl radicals and persistent radical anions. Gram-scale synthesis and diversification of drug derivatives have visualized the tremendous potential of this protocol for practical applications.

Polymyxin B exerts nephrotoxicity effects via inhibition of the Nrf2/NQO1 pathway-mediated antioxidant response.

Polymyxin B (PMB) is a polypeptide antibiotic widely used in treating multidrug-resistant Gram-negative bacteria. However, nephrotoxicity is a serious adverse effect that limits its clinical use. Therefore, clarification of the molecular mechanism of PMB-induced renal injury is essential. Our study aimed to explore possible mechanisms of PMB-induced nephrotoxicity in vivo and in vitro. Mice were treated with PMB to construct the kidney injury model. The antioxidant capacity was assessed by measuring the superoxide dismutase (SOD) and catalase (CAT) activities and the glutathione (GSH) and malondialdehyde (MDA) contents. The pathway of the nuclear factor erythroid 2-related factor 2/NADH quinone oxidoreductase 1 (Nrf2/NQO1) was examined after PMB treatment in NRK-52E cells and mice. Finally, the expressions of genes and proteins (Bax, Bcl-2, Caspase-3, Caspase-9) related to apoptosis were evaluated through quantitative polymerase chain reaction and western blot assay. The study verified PMB-induced nephrotoxicity in mice and NRK-52E cells in a dose- and time-dependent manner. PMB treatment significantly decreased the expression of Nrf2 and its downstream target gene NQO1 and increased the apoptosis-related proteins expression. In summary, our results suggested that PMB-induced oxidative stress damage by inhibiting the Nrf2/NQO1 pathway and promoting apoptosis in kidney tissues.

Burden of early-onset colorectal cancer along with attributable risk factors from 1990 to 2019: a comparative study between China and other G20 countries.

PURPOSE: The credible data about the burden of early-onset colorectal cancer (EOCRC) in China when compared to other countries in the group of twenty (G20) remained unavailable. We aimed to assess the burden and trends of EOCRC and attributable risk factors in China. Meanwhile, the comparison in the burden and attributable risk factors between China and other G20 countries was also evaluated. METHODS: Data on the incidence, prevalence, mortality, disability-adjusted life years (DALYs), and attributable risk factors of EOCRC in China were obtained from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 and compared with other G20countries. Temporal trends of age-standardized rates for incidence, prevalence, mortality, and DALYs were evaluated by estimated annual percentage change (EAPC). The autoregressive integrated moving average (ARIMA) model was used to forecast the incidence, mortality, and DALY rates of EOCRC in China from 2020 to 2029. RESULTS: From 1990 to 2019, the age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR) of EOCRC in China increased with the EAPCs of 4.61 [95% confidence interval (CI): 4.45-4.77] and 5.82 (95% CI: 5.60-6.05). When compared to G20 countries, China was ranked 13th in the ASIR in 1990 and then increased to 2nd in 2019, second only to Japan. The ASPRs increased in all G20 countries, being highest in Saudi Arabia, followed by China and Mexico. Moreover, China had the highest age-standardized mortality rate and highest age-standardized DALY rate in 2019. In China, the five leading risk factors, for both sexes, were diet low in milk [18.54% (95% UI: 12.71-24.07)], diet low in calcium [15.06% (95% UI: 10.70-20.03)], alcohol use [12.16% (95% UI: 8.87-15.64)], smoking [9.08% (95% UI: 3.39-14.11)], and diet high in red meat [9.08% (95% UI: 3.39-14.11)] in 2019. Over the next 10 years, ASIR, ASMR, and age-standardized DALY rate of EOCRC will increase continuously in males and females. CONCLUSION: The burden of EOCRC in China and other G20 countries is worrisome, indicating that coordinated efforts are needed to conduct high-quality researches, allocate medical resources, adjust screening guidelines, and develop effective treatment and prevention strategies in the G20 countries.

Burden and trends of mental disorders in China from 1990 to 2019: findings from the Global Burden of Disease Study 2019.

PURPOSE: Mental disorders remain the leading causes of disability worldwide. We aimed to determine the burden and trends of mental disorders in China from 1990 to 2019. METHODS: The incidence, prevalence, and disability-adjusted life years (DALYs) of mental disorders at national level of China were examined by age, sex, and subcategories. Temporal trends in the age-standardized rates for incidence, prevalence, and DALYs were assessed by the average annual percentage change (AAPC). All estimates are presented as numbers and age-standardized rates, with 95% uncertainty intervals (UIs). RESULTS: The number of incident cases due to mental disorders increased from 42.90 million to 52.72 million, the number of prevalent cases increased from 132.63 million to 160.16 million, and the number of DALYs increased from 15.64 million to 20.29 million during 1990-2019. Decreasing trends were observed in the age-standardized rates for incidence, prevalence and DALYs. Anxiety and depressive disorders were more frequent in women, while ADHD, conduct disorder, and autism spectrum disorders were more common in men. Compared with 1990, the age-specific incidence rates were higher in individuals under 14 years and over 55 years, whereas rates were lower in those aged 15-49 years in 2019. CONCLUSION: The number of incident cases, prevalent cases, and DALYs due to mental disorders gradually increased in China from 1990 to 2019. Anxiety and depressive disorders were the leading causes of burden due to mental disorders, which affected women more than men. Mental disorders deserve greater attention in health policy decision making.

Genetic landscape and autoimmunity of monocytes in developing Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder affecting multiple organs, including eyes, skin, and central nervous system. It is known that monocytes significantly contribute to the development of autoimmune disease. However, the subset heterogeneity with unique functions and signatures in human circulating monocytes and the identity of disease-specific monocytic populations remain largely unknown. Here, we employed an advanced single-cell RNA sequencing technology to systematically analyze 11,259 human circulating monocytes and genetically defined their subpopulations. We constructed a precise atlas of human blood monocytes, identified six subpopulations-including S100A12, HLA, CD16, proinflammatory, megakaryocyte-like, and NK-like monocyte subsets-and uncovered two previously unidentified subsets: HLA and megakaryocyte-like monocyte subsets. Relative to healthy individuals, cellular composition, gene expression signatures, and activation states were markedly alternated in VKH patients utilizing cell type-specific programs, especially the CD16 and proinflammatory monocyte subpopulations. Notably, we discovered a disease-relevant subgroup, proinflammatory monocytes, which showed a discriminative gene expression signature indicative of inflammation, antiviral activity, and pathologic activation, and converted into a pathologic activation state implicating the active inflammation during VKH disease. Additionally, we found the cell type-specific transcriptional signature of proinflammatory monocytes, ISG15, whose production might reflect the treatment response. Taken together, in this study, we present discoveries on accurate classification, molecular markers, and signaling pathways for VKH disease-associated monocytes. Therapeutically targeting this proinflammatory monocyte subpopulation would provide an attractive approach for treating VKH, as well as other autoimmune diseases.

Copper nanoparticles lead to reproductive dysfunction by affecting key enzymes of ovarian hormone synthesis and metabolism in female rats.

Studies on the general toxicity of copper nanoparticles (Cu NPs) have been conducted extensively, but their effects on reproductive toxicity remain unclear. In this study, we evaluated the toxic effect of Cu NPs on pregnant rats and their litter. The comparative in vivo toxicity of Cu ions, Cu NPs, and Cu microparticles (MPs) was studied in a 17-day repeated oral-dose experiment at the doses of 60, 120, and 180 mg/kg/day in pregnant rats. The pregnancy rate, mean live litter size, and number of dams decreased when exposed to Cu NPs. Moreover, Cu NPs caused a dose-dependent increase in ovarian Cu levels. The metabolomics results showed that Cu NPs caused reproductive dysfunction by altering sex hormones. In addition, in vivo and in vitro experiments showed that the ovarian cytochrome P450 enzymes (CYP450), responsible for hormone production, were significantly upregulated, whereas the enzymes responsible for hormone metabolism were significantly inhibited, resulting in a metabolic imbalance in some ovarian hormones. Furthermore, the results revealed that the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways significantly participated in the regulation of ovarian CYP enzyme expression. Overall, the results of the in vivo and in vitro toxicity experiments with Cu ions, Cu NPs, and Cu MPs suggested that toxicity from nanoscale Cu particles poses a more serious reproductive threat than microscale Cu as Cu NPs could directly damage the ovary and affect the metabolism of ovarian hormones.

Influence of monsoon anomalies on intra-annual density fluctuations of Chinese pine in the Loess Plateau.

In the past few decades, the East Asian summer monsoon (EASM) has experienced an unprecedented weakening, exacerbating drought in northern China, especially in the monsoon margin area. Improving our understanding of monsoon variability will benefit agricultural production, ecological construction, and disaster management. Tree-ring is widely used as proxy data for extending the monsoon history. However, in the East Asian monsoon margin, the tree-ring width were mostly formed before the rainy season, thus may have limited ability to indicate the monsoon variability. Intra-annual density fluctuations (IADFs) can provide higher resolution information on tree growth as well as evidence of short-term climate events. Here, we used Chinese pine (Pinus tabuliformis Carr.) samples from the eastern edge of the Chinese Loess Plateau (CLP), where the climate is deeply affected by monsoon, to investigate the response of tree growth and IADFs frequency to climate variation. We show that tree-ring width and IADFs record significantly different climatic signals. The former was mainly affected by moisture conditions at the end of the previous growing season and the current spring. While the latter was common in years when severe droughts occurred in June and July, especially in June. This period coincides with the onset of the EASM, so we further analyzed the relationship between IADFs frequency and the rainy season. Both correlation analysis and the GAM model suggest that the frequent occurrence of IADFs may be related to the late start of the monsoon rainy season, meaning that we have found a new indicator in tree-ring records that can capture monsoon anomalies. Our results provide further insight into drought variation in the eastern CLP, which also implicates the Asian summer monsoon dynamic.

Two-Step Matching Approach to Obtain More Control Points for SIFT-like Very-High-Resolution SAR Image Registration.

Airborne VHR SAR image registration is a challenging task. The number of CPs is a key factor for complex CP-based image registration. This paper presents a two-step matching approach to obtain more CPs for VHR SAR image registration. In the past decade, SIFT and other modifications have been widely used for remote sensing image registration. By incorporating feature point location affine transformation, a two-step matching scheme, which includes global and local matching, is proposed to allow for the determination of a much larger number of CPs. The proposed approach was validated by 0.5 m resolution C-band airborne SAR data acquired in Sichuan after the 2008 Wenchuan earthquake via a SAR system designed by the IECAS. With the proposed matching scheme, even the original SIFT, which is widely known to be unsuitable for SAR images, can achieve a much larger number of high-quality CPs than the one-step SIFT-OCT, which is tailored for SAR images. Compared with the classic one-step matching approach using both the SIFT and SITF-OCT algorithms, the proposed approach can obtain a larger number of CPs with improved precision.