The suppressive role of NLRP6 in host defense against Streptococcus suis infection.

Streptococcus suis (S. suis) disease is a prevalent zoonotic infectious threat that elicits a systemic inflammatory response in both swine and humans, frequently culminating in high mortality rates. The excessive inflammation triggered by S. suis infection can precipitate tissue damage and sudden death; however, a comprehensive strategy to mitigate this inflammatory response remains elusive. Our study examines the role of NLRP6 in S. suis infection, with a particular focus on its involvement in pathogen regulation. A marked upregulation of NLRP6 was observed in peritoneal macrophages post-infection with S. suis SC19 strain, consequently activating the NLRP6 inflammasome. Furthermore, SC19 infection was found to augment the secretion of pro-inflammatory cytokines IL-1ß via NLRP6 activation, while NLRP6 deficiency mitigates the invasion and adhesion of SC19 to macrophages. In vivo models revealed that NLRP6 deletion enhanced survival rates of SC19-infected mice, alongside a reduction in tissue bacterial load and inflammatory cytokine levels. NLRP6-/- mice were shown to exhibit attenuated inflammatory responses in pulmonary, hepatic, and splenic tissues post-SC19 infection, as evidenced by lower inflammation scores. Flow cytometry analyses further substantiated that NLRP6 is involved in modulating macrophage and neutrophil recruitment during infection. Our findings suggest that NLRP6 negatively regulates host resistance against S. suis infection; its absence results in reduced mortality, bacterial colonization, and a milder inflammatory response. Elucidating the mechanism of NLRP6 in S. suis-induced inflammation provides novel insights and theoretical underpinnings for the prophylaxis and therapeutics of S. suis diseases.

Interaction of general obesity and abdominal obesity with frailty in patients with chronic kidney disease: a nationally representative analysis.

Background: General and abdominal obesity are prevalent, with established associations to frailty in the elderly. However, few studies have investigated these associations in patients with chronic kidney disease (CKD), yielding inconsistent results. Methods: This cross-sectional study analysed data from the National Health and Nutrition Examination Survey (NHANES 2003-2018). Frailty was evaluated by the 36-item frailty index. General obesity was defined as a body mass index (BMI) >30 kg/m2; abdominal obesity was identified if waist circumference (WC) reached 102 cm in men and 88 cm in women. The associations of general and abdominal obesity with frailty were analysed using weighted multivariate logistic regression and restricted cubic splines. The interaction of general and abdominal obesity with frailty was examined. Results: A total of 5604 adult patients (median age 71 years, 42% men) with CKD were included in this analysis, with a median estimated glomerular filtration rate of 57.3 ml/min/1.73 m2. A total of 21% were frail with general obesity and 32% were frail with abdominal obesity. Neither general nor abdominal obesity alone was associated with frailty. There was an interaction between general and abdominal obesity with frailty. Compared with individuals with normal BMI and WC, those with both general and abdominal obesity, rather than either alone, exhibited significantly increased odds of frailty {odds ratio [OR] 1.53 [95% confidence interval (CI) 1.20-1.95]}. General obesity was associated with being frail only when CKD patients had abdominal obesity [OR 1.59 (95% CI 1.08-2.36)]. Conclusions: There may be an interaction between general and abdominal obesity with frailty in patients with CKD. Interventions aimed at preventing frailty should consider both aspects.

Assessment of prevalence of elevated blood lead levels and risk factors among children and pregnant women in Bihar, India.

BACKGROUND: While modeled estimates and studies in contaminated areas indicate high lead exposure among children in Bihar, India, local data on lead exposure in the child population is limited. OBJECTIVES: To characterize lead exposure, and assess potential sources of lead exposure among a state-representative sample of children and their pregnant mothers residing in Bihar. METHODS: Blood samples were collected from 697 children under five and 55 pregnant women from eight districts in Bihar. Blood lead levels were determined using capillary blood and a portable lead analyzer. Household demographics, home environment, behavior, and nutrition information were collected through computer-assisted personal interviews with primary caregivers. Logistic regression was used to assess associations between potential risk factors and elevated blood lead levels. RESULTS: More than 90% of children and 80% of pregnant women reported blood lead levels ≥5 µg/dL. Living near a lead-related industry and pica behavior of eating soil were significantly associated with increased odds of having elevated blood lead levels. Additional risk factors for having a blood level ≥5 µg/dL included the use of skin lightning cream (aOR = 5.11, 95%CI: 1.62, 16.16) and the use of eyeliners (aOR = 2.81, 95%CI: 1.14, 6.93). Having blood lead levels ≥10 µg/dL was also significantly associated with the household member who had an occupation or hobby involving the use of lead (aOR = 1.75, 95%CI: 1.13, 2.72). DISCUSSION: Elevated blood lead levels were prevalent among children and pregnant women in Bihar, indicating the urgent need for a comprehensive lead poisoning prevention strategy.

Detecting mir-155-3p through a Molecular Beacon Bead-Based Assay.

Lung cancer (LC) is recognized as one of the most prevalent and lethal cancers worldwide, underscoring an urgent need for innovative diagnostic and therapeutic approaches. MicroRNAs (miRNAs) have emerged as promising biomarkers for several diseases and their progression, such as LC. However, traditional methods for detecting and quantifying miRNAs, such as PCR, are time-consuming and expensive. Herein, we used a molecular beacon (MB) bead-based assay immobilized in a microfluidic device to detect miR-155-3p, which is frequently overexpressed in LC. The assay relies on the fluorescence enhancement of the MB upon binding to the target miRNA via Watson and Crick complementarity, resulting in a conformational change from a stem-loop to a linear structure, thereby bringing apart the fluorophores at each end. This assay was performed on a microfluidic platform enabling rapid and straightforward target detection. We successfully detected miR-155-3p in a saline solution, obtaining a limit of detection (LOD) of 42 nM. Furthermore, we evaluated the method's performance in more complex biological samples, including A549 cells' total RNA and peripheral blood mononuclear cells (PBMCs) spiked with the target miRNA. We achieved satisfactory recovery rates, especially in A549 cells' total RNA.

Ferritin and Serum Iron in a Causal Relationship with Estrogen Receptor-Negative Breast Cancer: a Two-Sample Mendelian Randomization Study.

BACKGROUND: The aim of this study was to explore the causal relationship between different serum iron statuses (ferritin, transferrin, transferrin saturation, and serum iron) and the occurrence of estrogen receptor (ER)-positive or ER-negative breast cancer. METHODS: The summary data on serum iron status exposure were gathered from the IEU OpenGWAS Project, the UK Biobank, and other databases. Concurrently, the summary data for ER+ and ER- breast cancer are sourced from the Breast Cancer Association Consortium (BCAC). By examining the causal link between iron status and breast cancer, we deployed five distinct Mendelian randomization (MR) algorithms, namely MR-Egger, inverse variance weighted (IVW), weighted median, simple mode, and MR-PRESSO. To assess heterogeneity and horizontal pleiotropy, Cochran's Q and MR-Egger algorithms were applied, respectively. RESULTS: Elevated ferritin levels are associated with an increased risk of ER-negative breast cancer (OR(IVW) = 1.042, 95% CI (1.005, 1.081), p = 0.025; OR (weighted median) = 1.050, 95% CI (1.001, 1.102), p = 0.046; and OR (MR-PRESSO) = 1.042, 95% CI (1.005, 1.081), p = 0.039). Conversely, an increase in the serum iron level is linked to a reduced risk of ER-negative breast cancer (OR (IVW) = 0.791, 95% CI (0.649, 0.962), p = 0.019; and OR (MR-PRESSO) = 0.791, 95% CI (0.649, 0.962), p = 0.028). However, there is no evidence of a causal relationship between transferrin, transferrin saturation, and ER-negative breast cancer. For ER-positive breast cancer, none of the four different iron statuses demonstrated a causal relationship. CONCLUSIONS: Ferritin is positively correlated with ER-negative breast cancer, while serum iron is negatively associated with ER-negative breast cancer. However, there is no causal relationship between the four iron statuses and ER-positive breast cancer.

Saccharopolyspora mangrovi sp. nov., a novel mangrove soil actinobacterium with distinct metabolic potential revealed by comparative genomic analysis.

A novel mangrove soil-derived actinomycete, strain S2-29T, was found to be most closely related to Saccharopolyspora karakumensis 5K548T based on 16 S rRNA sequence (99.24% similarity) and genomic phylogenetic analyses. However, significant divergence in digital DNA-DNA hybridization, average nucleotide identity, and unique biosynthetic gene cluster possession distinguished S2-29T as a distinct Saccharopolyspora species. Pan genome evaluation revealed exceptional genomic flexibility in genus Saccharopolyspora, with > 95% accessory genome content. Strain S2-29T harbored 718 unique genes, largely implicated in energetic metabolisms, indicating different metabolic capacities from its close relatives. Several uncharacterized biosynthetic gene clusters in strain S2-29T highlighted the strain's untapped capacity to produce novel functional compounds with potential biotechnological applications. Designation as novel species Saccharopolyspora mangrovi sp. nov. (type strain S2-29T = JCM 34,548T = CGMCC 4.7716T) was warranted, expanding the known Saccharopolyspora diversity and ecology. The discovery of this mangrove-adapted strain advances understanding of the genus while highlighting an untapped source of chemical diversity.

Tumor-intrinsic P2RY6 drives immunosuppression by enhancing PGE2 production.

Despite the success of anti-programmed cell death-1 (anti-PD-1) immunotherapy, many cancer patients remain unresponsive, and reliable predictive biomarkers are lacking. Here, we show that aberrant expression of the pyrimidinergic receptor P2RY6 is frequent in human cancers and causes immune evasion. In mouse syngeneic and human xenograft tumor models, ectopic expression of P2RY6 shapes an immunosuppressive tumor microenvironment (TME) to enhance tumor growth and resistance to immunotherapy, whereas deletion of P2RY6 from tumors with high P2RY6 expression inflames the TME to inhibit tumor growth. As a G protein-coupled receptor, P2RY6 activates Gq/phospholipase C-ß signaling and stimulates the synthesis of prostaglandin E2, which is a key mediator of immunosuppression in the TME. In contrast to the essential role of P2RY6 in tumors, global deletion of P2ry6 from mice does not compromise viability. Our study thus nominates P2RY6 as a precision immunotherapy target for patients with high tumor-intrinsic P2RY6 expression.

Rapid assessment of heavy metal accumulation capability of Sedum alfredii using hyperspectral imaging and deep learning.

Hyperaccumulators are the material basis and key to the phytoremediation of heavy metal contaminated soils. Conventional methods for screening hyperaccumulators are highly dependent on the time- and labor-consuming sampling and chemical analysis. In this study, a novel spectral approach assisted with multi-task deep learning was proposed to streamline accumulating ecotype screening, heavy metal stress discrimination, and heavy metals quantification in plants. The significant Cd/Zn co-hyperaccumulator Sedum alfredii and its non-accumulating ecotype were stressed by Cd, Zn, and Pb. Spectral images of leaves were rapidly acquired by hyperspectral imaging. The self-designed deep learning architecture was composed of a shallow network (ENet) for accumulating ecotype identification, and a multi-task network (HMNet) for heavy metal stress type and accumulation prediction simultaneously. To further assess the robustness of the networks, they were compared with conventional machine learning models (i.e., partial least squares (PLS) and support vector machine (SVM)) on a series of evaluation metrics of classification, multi-label classification, and regression. S. alfredii with heavy metals accumulation capability was identified by ENet with 100 % accuracy. HMNet reduced overfitting and outperformed machine learning models with the average exact match ratio (EMR) of heavy metal stress discrimination increased by 7.46 %, and residual prediction deviations (RPD) of heavy metal concentrations prediction increased by 53.59 %. The method succeeded in rapidly and accurately discriminating heavy metal stress with EMRs over 91 % and accuracies over 96 %, and in predicting heavy metals accumulation with an average RPD of 3.29 for Zn, 2.57 for Cd, and 2.53 for Pb, indicating the satisfactory practicability and potential for sensing heavy metals accumulation. This study provides a relatively novel spectral method to facilitate hyperaccumulator screening and heavy metals accumulation prediction in the phytoremediation process.

MMP11 as a prognostic biomarker correlated with immune infiltrates in pancreatic adenocarcinoma.

Background: Matrix metalloproteinase 11 (MMP11) plays a vital role in cell proliferation, apoptosis, tumor angiogenesis, migration, and other basic processes. Currently, few studies have examined the value of MMP11 in pancreatic cancer in relation to prognostic risk, diagnostic indicators, and immunotherapy. This study aims to explore the association between MMP11 and the tumor immune microenvironment in pancreatic adenocarcinoma (PAAD). Methods: We selected clinical samples and data downloaded from The Cancer Genome Atlas and Genotype-Tissue Expression, in addition, we use other online data for further analysis. Through a comprehensive bioinformatics investigation, we systematically analyzed the clinical significance and expression level of MMP11 in pancreatic cancer. Results: MMP11 was overexpressed in many cancers, and a higher expression of MMP11 was associated with a poorer prognosis in pancreatic cancer. Conversely, the hypermethylation of MMP11 was associated with better overall survival. The MMP11 expression network had widespread effects on the prognosis and immune activation of PAAD. The expression of MMP11 was significantly associated with a variety of tumor-infiltrating immune cells. An association was also found between MMP11 expression and chemokines in PAAD. High MMP11 expression might be involved in immune cell migration to the tumor microenvironment. Conclusions: MMP11 is a prognostic biomarker for patients in pancreatic cancer and may regulate the tumor immune microenvironment. The potential effects and mechanisms of MMP11 in PAAD require further exploring.

Nonlinear and abnormal relationship between turbidity and suspended solids concentration in mountainous rivers: A case study of the Lai Chi Wo river in Hong Kong, China.

Suspended solids concentration (SSC) in a river is closely relevant to river water turbidity. Investigation of their relationship in this study is accompanied by observed turbidity and SSC values, which were obtained from the testing results of water samples and monitored conditions in streamflow. The water samples were collected from two observation stations with a broad range of sediment concentrations in the Lai Chi Wo catchment in Hong Kong, China. We classified the target rainfall events into single-peak event type and dual-peak event type for a distinguished discussion of the relationship between SSC and turbidity in this study. At a finer classification, each event is separated into defined processes for the analysis, where two main processes refer to the periods that SSC rises from a normal state to a peak state first and the followed periods that SSC recesses to ordinary status gradually. It is advised by the analysis results that the estimation of SSC through turbidity values should be based on the same rainfall types for the upstream station. However, the results show that the classification of rainfall types does not need to take downstream areas into consideration. Furthermore, current research implies that the individual established connections between SSC and turbidity value at different stages (particularly referring to the rising period and recessing period) could be applied to estimate SSC at the same station via continuous turbidity values for both this and other ungauged stations with similar topographical features in the future. Meanwhile, this research approach provides new insight exploring various behaviors of sediments at different stages during an integral rainfall event. A comparison of distinguished performances of sediment during corresponding stages in a rainfall event makes contributions to diverse relationship between SSC and turbidity in the mountainous river.

Fluorogenic Aptamer Optimizations on a Massively Parallel Sequencing Platform.

F luorogenic ap tamers (FAPs) have become an increasingly important tool in cellular sensing and pathogen diagnostics. However, fine-tuning FAPs for enhanced performance remains challenging even with the structural details provided by X-ray crystallography. Here we present a novel approach to optimize a DNA-based FAP (D-FAP), Lettuce, on repurposed Illumina next-generation sequencing (NGS) chips. When substituting its cognate chromophore, DFHBI-1T, with TO1-biotin, Lettuce not only shows a red-shifted emission peak by 53 nm (from 505 to 558 nm), but also a 4-fold bulk fluorescence enhancement. After screening 8,821 Lettuce variants complexed with TO1-biotin, the C14T mutation is found to exhibit an improved apparent dissociated constant ( vs. 0.82 µM), an increased quantum yield (QY: 0.62 vs. 0.59) and an elongated fluorescence lifetime (τ: 6.00 vs. 5.77 ns), giving 45% more ensemble fluorescence than the canonical Lettuce/TO1-biotin complex. Molecular dynamic simulations further indicate that the π-π stacking interaction is key to determining the coordination structure of TO1-biotin in Lettuce. Our screening-and-simulation pipeline can effectively optimize FAPs without any prior structural knowledge of the canonical FAP/chromophore complexes, providing not only improved molecular probes for fluorescence sensing but also insights into aptamer-chromophore interactions.

Julolidinyl aza-BODIPYs as NIR-II fluorophores for the bioimaging of nanocarriers.

The aggregation-caused quenching (ACQ) rationale has been employed to improve the fluorescence imaging accuracy of nanocarriers by precluding free probe-derived interferences. However, its usefulness is undermined by limited penetration and low spatiotemporal resolution of NIR-I (700-900 nm) bioimaging owing to absorption and diffraction by biological tissues and tissue-derived autofluorescence. This study aimed to develop ACQ-based NIR-II (1000-1700 nm) probes to further improve the imaging resolution and accuracy. The strategy employed is to install highly planar and electron-rich julolidine into the 3,5-position of aza-BODIPY based on the larger substituent effects. The newly developed probes displayed remarkable photophysical properties, with intense absorption centered at approximately 850 nm and bright emission in the 950-1300 nm region. Compared with the NIR-I counterpart P2, the NIR-II probes demonstrated superior water sensitivity and quenching stability. ACQ1 and ACQ6 exhibited more promising ACQ effects with absolute fluorescence quenching at water fractions above 40% and higher quenching stability with less than 2.0% fluorescence reillumination in plasma after 24 h of incubation. Theoretical calculations verified that molecular planarity is more important than hydrophobicity for ACQ properties. Additionally, in vivo and ex vivo reillumination studies revealed less than 2.5% signal interference from prequenched ACQ1, in contrast to 15% for P2.

Preliminary Report of Nationwide COVID-19 Vaccine Compensation in Taiwan.

The potential adverse effects of coronavirus disease 2019 (COVID-19) vaccinations raise public concerns. Data from Taiwan's Vaccine Injury Compensation Program (VICP) can provide valuable insights. This study analyzed the preliminary application data for COVID-19 vaccine compensation in Taiwan's VICP, focusing on applicants receiving vaccines between March 2021 and June 2022. Among the 2941 adverse events, 113 cases (3.8%) were deemed causally associated with vaccination, 313 (10.6%) were indeterminate, and 2515 (85.5%) had no causal association. Nearly half (47.6%) of the applicants were over 60 years old, and 76.6% had a history of pre-existing chronic diseases. Among the 426 vaccine-associated or indeterminate cases, the most common causes were hematological diseases and thrombosis. There were 920 mortality cases reported, and 97.4% were unassociated with vaccination. Only five deaths were judged to be associated with the COVID-19 vaccination, all involving the adenovirus vector vaccine and thrombosis with thrombocytopenia syndrome. In conclusion, most compensation applications were not causally linked to vaccination. Compared to other countries, the number of applications in Taiwan's VICP is relatively high. These findings may indicate a need to adjust the application requirements for compensation in Taiwan's program.

Chemical constituents from a marine medicinal brown alga-derived Xylaria acuta SC1019.

In this study, a marine medicinal brown alga Sargassum cristaefolium-derived fungal strain Xylaria acuta SC1019 was isolated and identified. Column chromatography of the extracts from liquid- and solid-fermented products of the fungal strain was carried out, and led to the isolation of twenty-one compounds. Their structures were characterized by spectroscopic analysis, and the absolute configurations were further established by single X-ray diffraction analysis or modified Mosher's method as nine previously undescribed compounds, namely xylarilactones A-C (1-3), ent-gedebic acid 8-O-α-D-glucopyranoside (4), 5R-hydroxylmethylmellein 11-O-α-D-glucopyranoside (5), ent-hymatoxin E 16-O-α-D-mannopyranoside (6), 19,20-epoxycytochalasin S (7), 19,20-epoxycytochalasin T (8), and (2R)-butylitaconic acid (9), along with twelve known compounds 10-21. All the isolates were subjected to anti-inflammatory and anti-angiogenic assays. Compounds 1, 5, 7, 10, and 17 showed moderate nitric oxide production inhibitory activities in lipopolysaccharide-activated BV-2 microglial cells with IC50 values of 19.55 ± 0.35, 16.10 ± 0.57, 15.20 ± 0.87, 11.76 ± 0.49, and 11.30 ± 0.32 µM, respectively, as compared to curcumin (IC50 = 2.69 ± 0.34 µM) without any significant cytotoxicity. Compounds 7, 8, and 21 displayed potent anti-angiogenic activities by suppressing the growth of human endothelial progenitor cells with IC50 values of 0.44 ± 0.01, 0.47 ± 0.03, and 0.53 ± 0.01 µM, respectively, as compared to sorafenib (IC50 = 5.50 ± 1.50 µM).

The combination of detection and simulation for the distribution and sourcing of microplastics in Shing Mun River estuary, Hong Kong.

For the first time, combined detection and simulation was performed on microplastic (MP) debris in surface water, sediment, and oyster samples at ten coastal sites of Shing Mun River estuary, Hong Kong at different tidal conditions. The MP debris were extracted and detected using Fourier transform infrared (FT-IR) spectroscopy, and the simulation was conducted using Weather Research & Forecasting Model (WRF) / Regional Ocean Modelling System (ROMS) coupled hydro-dynamic modelling and the subsequent Lagrangian particle tracking. The results demonstrated the majority of polyethylene (with partial chlorine substitution) debris among all the MPs found, and great spatial and tidal variabilities of MP concentrations were observed. The combination of MP observation and simulations referred to the interpretation that a considerable percentage of MPs found in this study originated from South China Sea. Those MPs were probably transported to Tolo Harbour through sea currents and drifted inshore and offshore with tides. This study provided baseline measures of MP concentrations in Shing Mun River estuary and comprehensive understanding for how MPs transport and distribute within a dynamic estuarine system.

Evaluation of the outcomes of biliary-enteric reconstruction in robotic radical resection of hilar cholangiocarcinoma: a single-center propensity score matching analysis.

Although robotic radical resection for hilar cholangiocarcinoma (HCCA) has been reported in some large hepatobiliary centers, biliary-enteric reconstruction (BER) remains a critical step that hampers the operation's success. This study aimed to evaluate the feasibility and quality of BER in robotic radical resection of HCCA and propose technical recommendations. A retrospective study was conducted on patients with HCCA who underwent minimally invasive radical resection at Zhejiang Provincial People's Hospital between January 2016 and July 2023. A 1:2 propensity score matching (PSM), widely used to reduce selection bias, was performed to evaluate the outcomes, especially BER-related data, between the robotic and laparoscopic surgery. Forty-six patients with HCCA were enrolled; ten underwent robotic-assisted resection, while the others underwent laparoscopic surgery. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robot-assisted and laparoscopic groups, respectively. The baseline characteristics of both groups were generally well-balanced. The average liver resection time was longer in the robotic group than in the laparoscopic group (139.5 ± 38.8 vs 108.1 ± 35.8 min, P = 0.036). However, the former had less intraoperative blood loss [200 (50-500) vs 310 (100-850) ml], despite no statistical difference (P = 0.109). The number of residual bile ducts was 2.6 ± 1.3 and 2.7 ± 1.2 (P = 0.795), and anastomoses were both 1.6 ± 0.7 in the two groups (P = 0.965). The time of BER was 38.4 ± 13.6 and 59.1 ± 25.5 min (P = 0.024), accounting for 9.9 ± 2.8% and 15.4 ± 4.8% of the total operation time (P = 0.001). Although postoperative bile leakage incidence in laparoscopic group (40%) was higher than that in robotic group (10%), there was no significant difference between the two groups (P = 0.204); 6.7 ± 4.4 and 12.1 ± 11.7 days were observed for tube drawing (P = 0.019); anastomosis stenosis and calculus rate was 10% and 30% (P = 0.372), 0% and 15% (P = 0.532), respectively. Neither group had hemorrhage- or bile leakage-related deaths. Robotic radical resection for HCCA may offer perioperative outcomes comparable to conventional laparoscopic procedures and tends to be advantageous in terms of anastomosis time and quality. We are optimistic about its wide application in the future with the improvement of surgical techniques and experience.

Quantitative phosphoproteomics reveals molecular pathway network in wheat resistance to stripe rust.

Protein phosphorylation plays an important role in immune signaling transduction in plant resistance to pathogens. Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), severely devastates wheat production. Nonetheless, the molecular mechanism of wheat resistance to stripe rust remains limited. In this study, quantitative phosphoproteomics was employed to investigate the protein phosphorylation changes in wheat challenged by Pst. A total of 1537 and 2470 differentially accumulated phosphoproteins (DAPs) were identified from four early infection stage (6, 12, 18 and 24 h post-inoculation) in incompatible and compatible wheat-Pst interactions respectively. KEGG analysis revealed that Oxidative Phosphorylation, Phosphatidylinositol Signaling, and MAPK signaling processes are distinctively enriched in incompatible interaction, while Biosynthesis of secondary metabolites and RNA degradation process were significantly enriched in compatible interactions. In particular, abundant changes in phosphorylation levels of chloroplast proteins were identified, suggesting the regulatory role of photosynthesis in wheat-Pst interaction, which is further emphasized by protein-protein interaction (PPI) network analysis. Motif-x analysis identified [xxxxSPxxxx] motif, likely phosphorylation sites for defensive response-related kinases, and a new [xxxxSSxxxx] motif significantly enriched in incompatible interaction. The results shed light on the early phosphorylation events contributing to wheat resistance against Pst. Moreover, our study demonstrated that the phosphorylation levels of Nucleoside diphosphate kinase TaNAPK1 are upregulated at 12 hpi with CYR23 and at 24 hpi with CYR31. Transient silencing of TaNAPK1 was able to attenuate wheat resistance to CYR23 and CYR31. Our study provides new insights into the mechanisms underlying Pst-wheat interactions and may provide database to find potential targets for the development of new resistant varieties.

Visualization of oxygen vacancies and self-doped ligand holes in La3Ni2O7-δ.

The recent discovery of superconductivity in La3Ni2O7-δ under high pressure with a transition temperature around 80 K (ref. 1) has sparked extensive experimental2-6 and theoretical efforts7-12. Several key questions regarding the pairing mechanism remain to be answered, such as the most relevant atomic orbitals and the role of atomic deficiencies. Here we develop a new, energy-filtered, multislice electron ptychography technique, assisted by electron energy-loss spectroscopy, to address these critical issues. Oxygen vacancies are directly visualized and are found to primarily occupy the inner apical sites, which have been proposed to be crucial to superconductivity13,14. We precisely determine the nanoscale stoichiometry and its correlation to the oxygen K-edge spectra, which reveals a significant inhomogeneity in the oxygen content and electronic structure within the sample. The spectroscopic results also reveal that stoichiometric La3Ni2O7 has strong charge-transfer characteristics, with holes that are self-doped from Ni sites into O sites. The ligand holes mainly reside on the inner apical O and the planar O, whereas the density on the outer apical O is negligible. As the concentration of O vacancies increases, ligand holes on both sites are simultaneously annihilated. These observations will assist in further development and understanding of superconducting nickelate materials. Our imaging technique for quantifying atomic deficiencies can also be widely applied in materials science and condensed-matter physics.

Distinct biological signature and modifiable risk factors underlie the comorbidity between major depressive disorder and cardiovascular disease.

Major depressive disorder (MDD) and cardiovascular disease (CVD) are often comorbid, resulting in excess morbidity and mortality. Here we show that CVDs share most of their genetic risk factors with MDD. Multivariate genome-wide association analysis of shared genetic liability between MDD and atherosclerotic CVD revealed seven loci and distinct patterns of tissue and brain cell-type enrichments, suggesting the involvement of the thalamus. Part of the genetic overlap was explained by shared inflammatory, metabolic and psychosocial or lifestyle risk factors. Our data indicated causal effects of genetic liability to MDD on CVD risk, but not from most CVDs to MDD, and showed that the causal effects were partly explained by metabolic and psychosocial or lifestyle factors. The distinct signature of MDD-atherosclerotic CVD comorbidity suggests an immunometabolic subtype of MDD that is more strongly associated with CVD than overall MDD. In summary, we identified biological mechanisms underlying MDD-CVD comorbidity and modifiable risk factors for prevention of CVD in individuals with MDD.