Expansion of Pathogenic Cardiac Macrophages in Immune Checkpoint Inhibitor Myocarditis.

BACKGROUND: Immune checkpoint inhibitors (ICIs), antibodies targeting PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1) or CTLA4 (cytotoxic T-lymphocyte-associated protein 4), have revolutionized cancer management but are associated with devastating immune-related adverse events including myocarditis. The main risk factor for ICI myocarditis is the use of combination PD-1 and CTLA4 inhibition. ICI myocarditis is often fulminant and is pathologically characterized by myocardial infiltration of T lymphocytes and macrophages. Although much has been learned about the role of T-cells in ICI myocarditis, little is understood about the identity, transcriptional diversity, and functions of infiltrating macrophages. METHODS: We used an established murine ICI myocarditis model (Ctla4+/-Pdcd1-/- mice) to explore the cardiac immune landscape using single-cell RNA-sequencing, immunostaining, flow cytometry, in situ RNA hybridization, molecular imaging, and antibody neutralization studies. RESULTS: We observed marked increases in CCR2 (C-C chemokine receptor type 2)+ monocyte-derived macrophages and CD8+ T-cells in this model. The macrophage compartment was heterogeneous and displayed marked enrichment in an inflammatory CCR2+ subpopulation highly expressing Cxcl9 (chemokine [C-X-C motif] ligand 9), Cxcl10 (chemokine [C-X-C motif] ligand 10), Gbp2b (interferon-induced guanylate-binding protein 2b), and Fcgr4 (Fc receptor, IgG, low affinity IV) that originated from CCR2+ monocytes. It is important that a similar macrophage population expressing CXCL9, CXCL10, and CD16α (human homologue of mouse FcgR4) was expanded in patients with ICI myocarditis. In silico prediction of cell-cell communication suggested interactions between T-cells and Cxcl9+Cxcl10+ macrophages via IFN-γ (interferon gamma) and CXCR3 (CXC chemokine receptor 3) signaling pathways. Depleting CD8+ T-cells or macrophages and blockade of IFN-γ signaling blunted the expansion of Cxcl9+Cxcl10+ macrophages in the heart and attenuated myocarditis, suggesting that this interaction was necessary for disease pathogenesis. CONCLUSIONS: These data demonstrate that ICI myocarditis is associated with the expansion of a specific population of IFN-γ-induced inflammatory macrophages and suggest the possibility that IFN-γ blockade may be considered as a treatment option for this devastating condition.

Transcriptional and Immune Landscape of Cardiac Sarcoidosis.

BACKGROUND: Cardiac involvement is an important determinant of mortality among sarcoidosis patients. Although granulomatous inflammation is a hallmark finding in cardiac sarcoidosis, the precise immune cell populations that comprise the granuloma remain unresolved. Furthermore, it is unclear how the cellular and transcriptomic landscape of cardiac sarcoidosis differs from other inflammatory heart diseases. METHODS: We leveraged spatial transcriptomics (GeoMx digital spatial profiler) and single-nucleus RNA sequencing to elucidate the cellular and transcriptional landscape of cardiac sarcoidosis. Using GeoMX digital spatial profiler technology, we compared the transcriptomal profile of CD68+ rich immune cell infiltrates in human cardiac sarcoidosis, giant cell myocarditis, and lymphocytic myocarditis. We performed single-nucleus RNA sequencing of human cardiac sarcoidosis to identify immune cell types and examined their transcriptomic landscape and regulation. Using multichannel immunofluorescence staining, we validated immune cell populations identified by single-nucleus RNA sequencing, determined their spatial relationship, and devised an immunostaining approach to distinguish cardiac sarcoidosis from other inflammatory heart diseases. RESULTS: Despite overlapping histological features, spatial transcriptomics identified transcriptional signatures and associated pathways that robustly differentiated cardiac sarcoidosis from giant cell myocarditis and lymphocytic myocarditis. Single-nucleus RNA sequencing revealed the presence of diverse populations of myeloid cells in cardiac sarcoidosis with distinct molecular features. We identified GPNMB (transmembrane glycoprotein NMB) as a novel marker of multinucleated giant cells and predicted that the MITF (microphthalmia-associated transcription factor) family of transcription factors regulated this cell type. We also detected additional macrophage populations in cardiac sarcoidosis including HLA-DR (human leukocyte antigen-DR)+ macrophages, SYTL3 (synaptotagmin-like protein 3)+ macrophages and CD163+ resident macrophages. HLA-DR+ macrophages were found immediately adjacent to GPMMB+ giant cells, a distinct feature compared with other inflammatory cardiac diseases. SYTL3+ macrophages were located scattered throughout the granuloma and CD163+ macrophages, CD1c+ dendritic cells, nonclassical monocytes, and T cells were located at the periphery and outside of the granuloma. Finally, we demonstrate mTOR (mammalian target of rapamycin) pathway activation is associated with proliferation and is selectively found in HLA-DR+ and SYLT3+ macrophages. CONCLUSIONS: In this study, we identified diverse populations of immune cells with distinct molecular signatures that comprise the sarcoid granuloma. These findings provide new insights into the pathology of cardiac sarcoidosis and highlight opportunities to improve diagnostic testing.

Synergistic effects of silicon and goethite co-application in alleviating cadmium stress in rice (Oryza sativa L.): Insights into plant growth and iron plaque formation mechanisms.

Rice is one of the most important staple food crops; however, it is prone to cadmium (Cd) accumulation, which has negative health effects. Therefore, methods to reduce Cd uptake by rice are necessary. At present, there is limited research on the effects of co-application of silicon (Si) and goethite in mitigating Cd stress in rice. Furthermore, the specific mechanisms underlying the effects of their combined application on iron plaque formation in rice roots remain unclear. Therefore, this study analyzed the effects of the combined application of Si and goethite on the biomass, physiological stress indicators, Cd concentration, and iron plaques of rice using hydroponic experiments. The results revealed that co-treatment with both Si and goethite increased the plant height and dry weight, superoxide dismutase and catalase activities, photosynthetic pigment concentration, and root activity. Moreover, this treatment decreased the malondialdehyde concentration, repaired epidermal cells, reduced the Cd concentration in the roots by 57.2 %, and increased the number of iron plaques and Cd concentration by 150.9 % and 266.2 % in the amorphous and crystalline fractions, respectively. The Cd/Fe ratio in amorphous iron plaques also increased. Our findings suggest that goethite serves as a raw material for iron plaque formation, while Si enhances the oxidation capacity of rice roots. The application of a combination of Si and goethite increases the quantity and quality of iron plaques, enhancing its Cd fixation capacity. This study provides theoretical evidence for the effective inhibition of Cd uptake by iron plaques in rice, providing insights into methods for the remediation of Cd contamination.

[Association between the change in the job facilitating and inhibiting factors of care staff due to the employment of older assistant workers and the emotional exhaustion among care staff].

Objectives　The mental health condition of care staff in Japan is becoming problematic. Older assistant workers are currently being employed to assist care staff with their jobs and alleviate their job burden. This employment of older assistant workers is drawing attention; however, their influence on the job facilitating and inhibiting factors of care staff and the association with the care staff's emotional exhaustion remains unclear. In this study, we aim to examine how the employment of older care assistant workers relates to the job-facilitating and job-inhibiting factors of care staff and explore that association with the care staff's emotional exhaustion.Methods　Data from a mail survey of geriatric health services facilities with older assistant workers were analyzed. Among the answers obtained from the care staff, answers from 5,185 who reported working in facilities that employ older assistant workers (over the age of 60) were analyzed. The Emotional Exhaustion subscale of the Japanese Version of the Burnout Questionnaire was used as the dependent variable. The change in job-facilitating and job-inhibiting factors of care staff due to the employment of older assistant workers (improve, maintain/exacerbate) was explored for nine contents.Results　Care staff reported a decrease in the total volume of the task (63.6%), less stress during daily tasks (39.8%), and more concentration on the tasks that require expert care knowledge (38.0%). The results of multiple regression analysis showed that the emotional exhaustion score of care staff was low when the total volume of tasks decreased (ß=－0.383, 95%CI=－0.719, －0.047), when less stress was perceived during daily tasks (ß=－0.432, 95%CI=－0.796, －0.068), when concentration on tasks that required expert care knowledge increased (ß=－0.574, 95%CI=－0.937, －0.210), and when human relationships among staff improved (ß=－0.871, 95%CI=－1.263, －0.480). Conversely, an increase in tasks requiring work with regional personnel and organizations (ß=0.800, 95%CI=0.162, 1.437) was associated with a high emotional exhaustion score.Conclusion　The employment of older care workers was related to the job-facilitating or job-inhibiting factors of care staff, and the change in these factors was associated with lower emotional exhaustion. The employment of older personnel may lower the risk of burnout among care staff.

CCL17 Aggravates Myocardial Injury by Suppressing Recruitment of Regulatory T Cells.

BACKGROUND: Recent studies have established that CCR2 (C-C chemokine receptor type 2) marks proinflammatory subsets of monocytes, macrophages, and dendritic cells that contribute to adverse left ventricle (LV) remodeling and heart failure progression. Elucidation of the effector mechanisms that mediate adverse effects of CCR2+ monocytes, macrophages, and dendritic cells will yield important insights into therapeutic strategies to suppress myocardial inflammation. METHODS: We used mouse models of reperfused myocardial infarction, angiotensin II and phenylephrine infusion, and diphtheria toxin cardiomyocyte ablation to investigate CCL17 (C-C chemokine ligand 17). We used Ccl17 knockout mice, flow cytometry, RNA sequencing, biochemical assays, cell trafficking studies, and in vivo cell depletion to identify the cell types that generate CCL17, define signaling pathways that controlled its expression, delineate the functional importance of CCL17 in adverse LV remodeling and heart failure progression, and determine the mechanistic basis by which CCL17 exerts its effects. RESULTS: We demonstrated that CCL17 is expressed in CCR2+ macrophages and cluster of differentiation 11b+ conventional dendritic cells after myocardial infarction, angiotensin II and phenylephrine infusion, and diphtheria toxin cardiomyocyte ablation. We clarified the transcriptional signature of CCL17+ macrophages and dendritic cells and identified granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling as a key regulator of CCL17 expression through cooperative activation of STAT5 (signal transducer and activator of transcription 5) and canonical NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells) signaling. Ccl17 deletion resulted in reduced LV remodeling, decreased myocardial fibrosis and cardiomyocyte hypertrophy, and improved LV systolic function after myocardial infarction and angiotensin II and phenylephrine infusion. We observed increased abundance of regulatory T cells (Tregs) in the myocardium of injured Ccl17 knockout mice. CCL17 inhibited Treg recruitment through biased activation of CCR4. CCL17 activated Gq signaling and CCL22 (C-C chemokine ligand 22) activated both Gq and ARRB (ß-arrestin) signaling downstream of CCR4. CCL17 competitively inhibited CCL22 stimulated ARRB signaling and Treg migration. We provide evidence that Tregs mediated the protective effects of Ccl17 deletion on myocardial inflammation and adverse LV remodeling. CONCLUSIONS: These findings identify CCL17 as a proinflammatory mediator of CCR2+ macrophages and dendritic cells and suggest that inhibition of CCL17 may serve as an effective strategy to promote Treg recruitment and suppress myocardial inflammation.

Stronger susceptibilities to air pollutants of influenza A than B were identified in subtropical Shenzhen, China.

Air pollution was indicated to be a key factor contributing to the aggressive spread of influenza viruses, whereas uncertainty still exists regarding to whether distinctions exist between influenza subtypes. Our study quantified the impact of five air pollutants on influenza subtype outbreaks in Shenzhen, China, a densely populated and highly urbanized megacity. Daily influenza outbreak data of laboratory-confirmed positive cases were obtained from the Shenzhen CDC, from May 1, 2013 to Dec 31, 2015. Concentrations of nitrogen dioxide (NO2), sulfur dioxide (SO2), particulate matters ≤2.5 µm (PM2.5), particulate matters ≤10 µm (PM10), and ozone (O3), were retrieved from the 18 national monitoring stations. The generalized additive model (GAM) and distributed lag non-linear model (DLNM) were used to calculate the concentration-response relationships between environmental inducers and outbreak epidemics, respectively for influenza A (Flu-A) and B (Flu-B). There were 1687 positive specimens were confirmed during the study period. The cold season was restricted from Nov. 4th to Apr. 20th, covering all seasons other than the long-lasting summer. Relatively heavy fine particle matter (PM2.5) and NO2 pollution was observed in cold months, with mean concentrations of 46.06 µg/m3 and 40.03 µg/m3, respectively. Time-series analysis indicated that high concentrations of NO2, PM2.5, PM10, and O3 were associated with more influenza outbreaks at short lag periods (0-5 d). Although more Flu-B (679 cases) epidemics occurred than Flu-A (382 cases) in the cold season, Flu-A generally showed higher susceptibility to air pollutants. A 10 µg/m3 increment in concentrations of PM2.5, PM10, and O3 at lag 04, was associated with a 2.103 (95%CI: 1.528-2.893), 1.618 (95%CI: 1.311-1.996), and 1.569 (95%CI: 1.214-2.028) of the relative risk (RR) of Flu-A, respectively. A 5 µg/m3 increase in NO2 was associated with higher risk of Flu-A at lag 03 (RR = 1.646, 95%CI: 1.295-2.092) and of Flu-B at lag 04 (RR = 1.319, 95%CI: 1.095-1.588). Nevertheless, barely significant effect of particulate matters (PM2.5, PM10) on Flu-B and SO2 on both subtypes was detected. Further, the effect estimates of NO2 increased for both subtypes when coexisting with other pollutants. This study provides evidence that declining concentrations of main pollutants including NO2, O3, and particulate matters, could substantially decrease influenza risk in subtropical Shenzhen, especially for influenza A.

Osteogenic effect and mechanism of IL-10 in diabetic rat jaw defect mode.

OBJECTIVE: The aim of this study was to investigate the effect of IL-10 on the phenotype polarization of macrophages and osteogenesis in diabetes mellitus type 2 (T2DM) rat jaw defects. METHODS: Lipopolysaccharide (LPS) and interleukin-10 (IL-10) were chosen to induce the polarization of macrophages. In vitro assessment included wound-healing assay, western blotting, and alizarin red staining after co-culture of the bone marrow-derived mesenchymal stem cells (BMSCs) and induced macrophages. For in vivo study, IL-10 was loaded on GelMA-Heparin and applied to bone defects of the alveolar ridge in diabetic rats, while Bio-Oss Collagen, simple GelMA-Heparin, and blank control groups were set for contrast experiment. The mandibles of rats were processed for micro-computed tomography, histology, and immunohistochemistry 1 week and 4 weeks after the operation. RESULTS: IL-10 induced expression of arginase 1, TGF-ß1, EGR2, and Mannose Receptor (CD206), whereas LPS induced expression of iNOS, TNF-α, IL-6, CD80. The BMSCs co-cultured with macrophages induced by IL-10 showed increased migration, osteogenic differentiation, and mineralization in vitro. Notably, the IL-10-laden GelMA-Heparin group showed quicker new bone formation and a higher M2/M1 ratio of macrophages in the jawbone defect area compared with the control groups. CONCLUSIONS: IL-10 can stably induce macrophages to M2 type, thereby influencing BMSCs and improving the osteogenesis of jaw bone defects.

Cadmium distribution and transformation in leaf cells involved in detoxification and tolerance in barley.

Barley is a diagnostic plant that often used in the research of soil pollution by heavy metals, our research explored the detoxification and tolerance mechanism of cadmium(Cd) in barley through pot experiment. We investigated subcellular distribution, chemical forms and oxidative damage of Cd in barley leaves, combing with the transmission electron microscopy and Fourier-transform infrared spectroscopy(FT-IR) to further understand the translocation, transformation characteristics and toxic effect of Cd in cells. The results showed that, the bioaccumulation factors in roots and shoots of barley were ranged of 4.03-7.48 and 0.51-1.30, respectively. Barley reduces the toxic effects by storing Cd in the roots and reducing its transport to the shoots. Compared to the control treatment (0 mg/kg), the percentage of Cd in the cell wall fractions of leaves in 300 mg/kg Cd treatment increased from 34.74 % to 38.41 %; the percentage of the organelle fractions increased from 24.47 % to 56.02 %; and the percentage of soluble fraction decreased from 40.80 % to 5.57 %. We found that 69.13 % of the highly toxic inorganic Cd and water-soluble Cd were converted to less toxic pectates and protein-integrated Cd (50.20 %) and undissolved Cd phosphates (18.93 %). This conversion of Cd was mainly due to its combination with -OH, -NH, -CN, -C-O-C, and -C-O-P groups. Excessive Cd induced a significant (P < 0.05) increase in the levels of peroxidase, malondialdehyde, and cell membrane permeability, which damaged the cell membrane and allowed Cd to enter the organelles. The chloroplasts and mitochondria were destroyed, and eventually the metabolism of intracellular substances was affected, resulting in symptoms of toxicity. Our research provides cellular-scale insight into the mechanisms of Cd tolerance in barley.

Cytogenetic Characterization and Molecular Marker Development for a Wheat-T. boeoticum 4Ab (4B) Disomic Substitution Line with Stripe Rust Resistance.

Triticum boeoticum (2n = 2x = 14, AbAb) is an important relative of wheat. This species tolerates many different types of environmental stresses, including drought, salt, and pathogenic infection, and is lower in dietary fiber and higher in antioxidants, protein (15 to 18%), lipids, and trace elements than common wheat. However, the gene transfer rate from this species to common wheat is low, and few species-specific molecular markers are available. In this study, the wheat-T. boeoticum substitution line Z1889, derived from a cross between the common wheat cultivar Crocus and T. boeoticum line G52, was identified using multicolor fluorescence in situ hybridization, multicolor genomic in situ hybridization, and a 55K single-nucleotide polymorphism array. Z1889 was revealed to be a 4Ab (4B) substitution line with a high degree of resistance to stripe rust pathogen strains prevalent in China. In addition, 22 4Ab chromosome-specific molecular markers and 11 T. boeoticum genome-specific molecular markers were developed from 1,145 4Ab chromosome-specific fragments by comparing the sequences generated by specific-length amplified fragment sequencing, with an efficiency of up to 55.0%. Furthermore, the specificity of these markers was verified in four species containing the Ab genome. These markers not only can be used for the detection of the 4Ab chromosome but also provide a basis for molecular marker-assisted, selection-based breeding in wheat.

FedRAD: Heterogeneous Federated Learning via Relational Adaptive Distillation.

As the development of the Internet of Things (IoT) continues, Federated Learning (FL) is gaining popularity as a distributed machine learning framework that does not compromise the data privacy of each participant. However, the data held by enterprises and factories in the IoT often have different distribution properties (Non-IID), leading to poor results in their federated learning. This problem causes clients to forget about global knowledge during their local training phase and then tends to slow convergence and degrades accuracy. In this work, we propose a method named FedRAD, which is based on relational knowledge distillation that further enhances the mining of high-quality global knowledge by local models from a higher-dimensional perspective during their local training phase to better retain global knowledge and avoid forgetting. At the same time, we devise an entropy-wise adaptive weights module (EWAW) to better regulate the proportion of loss in single-sample knowledge distillation versus relational knowledge distillation so that students can weigh losses based on predicted entropy and learn global knowledge more effectively. A series of experiments on CIFAR10 and CIFAR100 show that FedRAD has better performance in terms of convergence speed and classification accuracy compared to other advanced FL methods.

Identification of the Solid Stem Suppressor Gene Su-TdDof in Synthetic Hexaploid Wheat Syn-SAU-117.

Lodging is one of the most important factors affecting the high and stable yield of wheat worldwide. Solid-stemmed wheat has higher stem strength and lodging resistance than hollow-stemmed wheat does. There are many solid-stemmed varieties, landraces, and old varieties of durum wheat. However, the transfer of solid stem genes from durum wheat is suppressed by a suppressor gene located on chromosome 3D in common wheat, and only hollow-stemmed lines have been created. However, synthetic hexaploid wheat can serve as a bridge for transferring solid stem genes from tetraploid wheat to common wheat. In this study, the F1, F2, and F2:3 generations of a cross between solid-stemmed Syn-SAU-119 and semisolid-stemmed Syn-SAU-117 were developed. A single dominant gene, which was tentatively designated Su-TdDof and suppresses stem solidity, was identified in synthetic hexaploid wheat Syn-SAU-117 by using genetic analysis. By using bulked segregant RNA-seq (BSR-seq) analysis, Su-TdDof was mapped to chromosome 7DS and flanked by markers KASP-669 and KASP-1055 within a 4.53 cM genetic interval corresponding to 3.86 Mb and 2.29 Mb physical regions in the Chinese Spring (IWGSC RefSeq v1.1) and Ae. tauschii (AL8/78 v4.0) genomes, respectively, in which three genes related to solid stem development were annotated. Su-TdDof differed from a previously reported solid stem suppressor gene based on its origin and position. Su-TdDof would provide a valuable example for research on the suppression phenomenon. The flanking markers developed in this study might be useful for screening Ae. tauschii accessions with no suppressor gene (Su-TdDof) to develop more synthetic hexaploid wheat lines for the breeding of lodging resistance in wheat and further cloning the suppressor gene Su-TdDof.

Femtosecond Time-Resolved Neighbor Roles in the Fragmentation Dynamics of Molecules in a Dimer.

How the neighbor effect plays its role in the fragmentation of molecular clusters attracts great attention for physicists and chemists. Here, we study this effect in the fragmentation of N_{2}O dimer by performing three-body coincidence measurements on the femtosecond timescale. Rotations of bound N_{2}O^{+} triggered by neutral or ionic neighbors are tracked. The forbidden dissociation path between B^{2}Π and ^{4}Π is opened by the spin-exchange effect due to the existence of neighbor ions, leading to a new channel of N_{2}O^{+}→NO+N^{+} originating from B^{2}Π. The formation and dissociation of the metastable product N_{3}O_{2}^{+} from two ion-molecule reaction channels are tracked in real time, and the corresponding trajectories are captured. Our results demonstrate a significant and promising step towards the understanding of neighbor roles in the reactions within clusters.

Natural bioactive constituents from herbs and nutraceuticals promote browning of white adipose tissue.

Obesity is a significant public health problem worldwide that is characterized by abnormal or excessive fat accumulation. Unfortunately, the application of available weight-loss drugs has been restricted because of their serious adverse effects. Browning of white adipose tissue (WAT), which refers to the transformation of white adipocytes to beige adipocytes under certain stimulations, is regarded as a new strategy to solve the obesity problem. Numerous studies have recently evidenced that traditional Chinese medicine (TCM) could promote browning of WAT with multi-component and multi-target characteristics. This article summarizes natural constituents from TCM with stimulatory effects on browning of WAT in the past two decades. The active ingredients can be generally divided into polyphenols, saponins, alkaloids, terpenoids, phenylpropanoids and others, such as resveratrol, quercetin, curcumin, genistein, capsaicin, epigallocatechin gallate (EGCG), berberine, menthol, emodin and ginsenosides. Simultaneously, the chemical structures, source, model, efficacy and mechanism of these monomeric compounds are also described. And the mechanisms of these active ingredients are mainly involved in the regulation of PRDM16, PGC-1α, PPARγ, SIRT1, AMPK, ß3-adrenergic receptors, TRPV1 and TRPM8 channels, FGF21 and miRNAs. The present article opens opportunities for developing novel drugs or supplements from TCM with wide acceptability to prevent obesity progression and its associated metabolic disorders.

Genetic Polymorphism of 24 Autosomal STR in the Population of Rwanda.

Rwanda is one of the smallest countries of Africa, where forensic genetic studies are rarely being conducted and very few DNA databases have been developed. Short tandem repeats (STRs) polymorphisms were investigated in 505 unrelated Rwandese by using the HUMDNA TYPING (Yanhuang) Kit. The following STRs were targeted: D3S1358, D13S317, D7S820, D16S539, SE33, D10S1248, D5S818, D21S11, TPOX, D1S1656, D6S1043, D19S433, D22S1045, D8S1179, Penta E, D2S441, D12S391, D2S1338, vWA, Penta D, TH01, D18S51, CSF1PO and FGA. The purpose of this study was to elucidate the genetic diversity and explore the potential of applying these 24 STR in 505 Rwandan population in forensics. A total of 360 alleles, with corresponding allele frequencies in the range from 0.001 to 0.442, were found in the Rwandan population. SE33 presented the highest polymorphism (PIC=0.921) among these 24 loci, whereas D13S317 presented the lowest one (PIC=0.671). No deviation from the Hardy-Weinberg equilibrium was observed for any of the 24 loci. The forensic parameters, including the combined power of discrimination (PD and the combined exclusion power, have demonstrated that this panel of 24 STRs is highly informative and useful for forensic applications such as individuals' identification and paternity tests. Additionally, the genetic distances between Rwanda population and other 24 published populations were calculated based on 8 overlapping loci with the polygenetic tree revealing significant clusters in the populations associated with their geographic locations and their historical relationship.

Influenza A and B outbreaks differed in their associations with climate conditions in Shenzhen, China.

Under the variant climate conditions in the transitional regions between tropics and subtropics, the impacts of climate factors on influenza subtypes have rarely been evaluated. With the available influenza A (Flu-A) and influenza B (Flu-B) outbreak data in Shenzhen, China, which is an excellent example of a transitional marine climate, the associations of multiple climate variables with these outbreaks were explored in this study. Daily laboratory-confirmed influenza virus and climate data were collected from 2009 to 2015. Potential impacts of daily mean/maximum/minimum temperatures (T/Tmax/Tmin), relative humidity (RH), wind velocity (V), and diurnal temperature range (DTR) were analyzed using the distributed lag nonlinear model (DLNM) and generalized additive model (GAM). Under its local climate partitions, Flu-A mainly prevailed in summer months (May to June), and a second peak appeared in early winter (December to January). Flu-B outbreaks usually occurred in transitional seasons, especially in autumn. Although low temperature caused an instant increase in both Flu-A and Flu-B risks, its effect could persist for up to 10 days for Flu-B and peak at 17 C (relative risk (RR) = 14.16, 95% CI: 7.46-26.88). For both subtypes, moderate-high temperature (28 C) had a significant but delayed effect on influenza, especially for Flu-A (RR = 26.20, 95% CI: 13.22-51.20). The Flu-A virus was sensitive to RH higher than 76%, while higher Flu-B risks were observed at both low (< 65%) and high (> 83%) humidity. Flu-A was active for a short term after exposure to large DTR (e.g., DTR = 10 C, RR = 12.45, 95% CI: 6.50-23.87), whereas Flu-B mainly circulated under stable temperatures. Although the overall wind speed in Shenzhen was low, moderate wind (2-3 m/s) was found to favor the outbreaks of both subtypes. This study revealed the thresholds of various climatic variables promoting influenza outbreaks, as well as the distinctions between the flu subtypes. These data can be helpful in predicting seasonal influenza outbreaks and minimizing the impacts, based on integrated forecast systems coupled with short-term climate models.

A Solvent-Mediated Excited-State Intermolecular Proton Transfer Fluorescent Probe for Fe3+ Sensing and Cell Imaging.

Constructing excited-state intermolecular proton transfer (ESIPT-e) fluorophores represents significant challenges due to the harsh requirement of bearing a proton donor-acceptor (D-A) system and their matching proton donating-accepting ability in the same molecule. Herein, we synthesized a new-type ESIPT-e fluorophor (2-APC) using the "four-component one-pot" reaction. By the installing of a cyano-group on pyridine scaffold, the proton donating ability of -NH2 was greatly enhanced, enabling 2-APC to undergo ESIPT-e process. Surprisingly, 2-APC exhibited dual-emissions in protic solvents ethanol and normal fluorescence in aprotic solvents, which is vastly different from that of conventional ESIPT-a dyes. The ESIPT emission can be obviously suppressed by Fe3+ due to the coordination reaction of Fe3+ with the A-D system in 2-APC. From this basis, a highly sensitive and selective method was established using 2-APC as a fluorescent probe, which offers the sensitive detection of Fe3+ ranging from 0 to 13 µM with the detection limit of 7.5 nM. The recovery study of spiked Fe3+ measured by the probe showed satisfactory results (97.2103.4%) with the reasonable RSD ranging from 3.1 to 3.8%. Moreover, 2-APC can also exhibit aggregation-induced effect in poor solvent or solid-state, eliciting strong red fluorescence. 2-APC was also applied to cell-imaging, exhibiting good cell-permeability, biocompatibility and color rendering. This multi-mode emission of 2-APC is significant departure from that of conventional extended p-conjugated systems and ESIPT dyes based on a flat and rigid molecular design. The "one-pot synthesis" strategy for the construction of ESIPT molecules pioneered a new route to achieve tricolor-emissive fluorophores.

Partnered Excited-State Intermolecular Proton Transfer Fluorescence (P-ESIPT) Signaling for Nitrate Sensing and High-Resolution Cell-Imaging.

Nitrite (NO2-) is a common pollutant and is widely present in the environment and in human bodies. The development of a rapid and accurate method for NO2- detection is always a very important task. Herein, we synthesized a partnered excited-state intermolecular proton transfer (ESIPT) fluorophore using the "multi-component one pot" method, and used this as a probe (ESIPT-F) for sensing NO2-. ESIPT-F exhibited bimodal emission in different solvents because of the solvent-mediated ESIPT reaction. The addition of NO2- caused an obvious change in colors and tautomeric fluorescence due to the graft of NO2- into the ESIPT-F molecules. From this basis, highly sensitive and selective analysis of NO2- was developed using tautomeric emission signaling, achieving sensitive detection of NO2- in the concentration range of 0~45 mM with a detection limit of 12.5 nM. More importantly, ESIPT-F showed the ability to anchor proteins and resulted in a recognition-driven "on-off" ESIPT process, enabling it to become a powerful tool for fluorescence imaging of proteins or protein-based subcellular organelles. MTT experimental results revealed that ESIPT-F is low cytotoxic and has good membrane permeability to cells. Thus, ESIPT-F was further employed to image the tunneling nanotube in vitro HEC-1A cells, displaying high-resolution performance.

Revealing Molecular Strong Field Autoionization Dynamics.

The novel strong field autoionization (SFAI) dynamics is identified and investigated by channel-resolved angular streaking measurements of two electrons and two ions for the double-ionized CO. Comparing with the laser-assisted autoionization calculations, we demonstrate the electrons from SFAI are generated from the field-induced decay of the autoionizing state with a following acceleration in the laser fields. The energy-dependent photoelectron angular distributions further reveal that the subcycle ac-Stark effect modulates the lifetime of the autoionizing state and controls the emission of SFAI electrons in molecular frame. Our results pave the way to control the emission of resonant high-harmonic generation and trace the electron-electron correlation and electron-nuclear coupling by strong laser fields. The lifetime modulation of quantum systems in the strong laser field has great potential for quantum manipulation of chemical reactions and beyond.

Design and Implementation of a Novel Interferometric Microwave Radiometer for Human Body Temperature Measurement.

In this paper, the key technology of interferometric microwave thermometer is studied, the research can be applied to the temperature measurement of human body and subcutaneous tissue. This paper proposes a hardware architecture of interferometric microwave thermometer with 2 GHz bandwidth, in which the phase shifter is used to correct phase error and the quadrature demodulator is used to realize autocorrelation detection function. The results show that when input power is 7 dBm, the detection sensitivity can reach 176.54 mV/dBm and the temperature resolution of the microwave radiometer can reach 0.4 K. Correction algorithm is designed to improve the accuracy of temperature measurement. After correction, the phase error is reduced from 40° to 1.4° and when temperature changes 0.1 °C, the voltage value changes obviously. Step-by-step calibration and overall calibration are used to calibrate the device. Inversion algorithm can determine the relationship between physical temperature and output voltage. The mean square error of water temperature inversion by multiple linear regression algorithm is 0.607 and that of BP neural network algorithm is 0.334. The inversion accuracy can be improved by reducing the temperature range. Our work provides a promising realization of accurate, rapid and non-contact detection device of human body temperature.

Low-RF-loss and large-rejection reconfigurable Brillouin-based RF photonic bandpass filter.

We present a high-performance radio frequency (RF) photonic bandpass filter enabled by combining on-chip Brillouin scattering with a suppressed carrier phase modulation scheme. We achieve a low RF loss of 5 dB and a large stopband rejection of more than 40 dB, which represents a significant improvement of 20 dB to the RF passband gain and 31 dB to the RF rejection ratio over traditional modulation schemes under the same optical power consumption. We further demonstrate filter reconfigurability including multiple passbands, wide frequency (1-20 GHz), and bandwidth tunability (30-350 MHz) without compromising the RF performance.