Population-level exploration of alternative splicing and its unique role in controlling agronomic traits of rice.

Alternative splicing (AS) plays crucial roles in regulating various biological processes in plants. However, the genetic mechanisms underlying AS and its role in controlling important agronomic traits in rice (Oryza sativa) remain poorly understood. In this study, we explored AS in rice leaves and panicles using the rice minicore collection. Our analysis revealed a high level of transcript isoform diversity, with approximately one-fifth of the potential isoforms acting as major transcripts in both tissues. Regarding the genetic mechanism of AS, we found that the splicing of 833 genes in the leaf and 1,230 genes in the panicle was affected by cis-genetic variation. Twenty-one percent of these AS events could only be explained by large structural variations. Approximately 77.5% of genes with significant splicing quantitative trait loci (sGenes) exhibited tissue-specific regulation, and AS can cause 26.9% (leaf) and 23.6% (panicle) of sGenes to have altered, lost, or gained functional domains. Additionally, through splicing-phenotype association analysis, we identified phosphate-starvation-induced RING-type E3 ligase (OsPIE1; LOC_Os01g72480), whose splicing ratio was significantly associated with plant height. In summary, this study provides an understanding of AS in rice and its contribution to the regulation of important agronomic traits.

mRNA cleavage by 21-nucleotide phasiRNAs determines temperature-sensitive male sterility in rice.

Temperature-sensitive male sterility is one of the core components for hybrid rice (Oryza sativa) breeding based on the 2-line system. We previously found that knockout of ARGONAUTE 1d (AGO1d) causes temperature-sensitive male sterility in rice by influencing phased small interfering RNA (phasiRNA) biogenesis and function. However, the specific phasiRNAs and their targets underlying the temperature-sensitive male sterility in the ago1d mutant remain unknown. Here, we demonstrate that the ago1d mutant displays normal female fertility but complete male sterility at low temperature. Through a multiomics analysis of small RNA (sRNA), degradome, and transcriptome, we found that 21-nt phasiRNAs account for the greatest proportion of the 21-nt sRNA species in rice anthers and are sensitive to low temperature and markedly downregulated in the ago1d mutant. Moreover, we found that 21-nt phasiRNAs are essential for the mRNA cleavage of a set of fertility- and cold tolerance-associated genes, such as Earlier Degraded Tapetum 1 (EDT1), Tapetum Degeneration Retardation (TDR), OsPCF5, and OsTCP21, directly or indirectly determined by AGO1d-mediated gene silencing. The loss of function of 21-nt phasiRNAs can result in upregulation of their targets and causes varying degrees of defects in male fertility and grain setting. Our results highlight the essential functions of 21-nt phasiRNAs in temperature-sensitive male sterility in rice and suggest their promising application in 2-line hybrid rice breeding in the future.

A rice variation map derived from 10 548 rice accessions reveals the importance of rare variants.

Detailed knowledge of the genetic variations in diverse crop populations forms the basis for genetic crop improvement and gene functional studies. In the present study, we analyzed a large rice population with a total of 10 548 accessions to construct a rice super-population variation map (RSPVM), consisting of 54 378 986 single nucleotide polymorphisms, 11 119 947 insertion/deletion mutations and 184 736 presence/absence variations. Assessment of variation detection efficiency for different population sizes revealed a sharp increase of all types of variation as the population size increased and a gradual saturation of that after the population size reached 10 000. Variant frequency analysis indicated that ∼90% of the obtained variants were rare, and would therefore likely be difficult to detect in a relatively small population. Among the rare variants, only 2.7% were predicted to be deleterious. Population structure, genetic diversity and gene functional polymorphism of this large population were evaluated based on different subsets of RSPVM, demonstrating the great potential of RSPVM for use in downstream applications. Our study provides both a rich genetic basis for understanding natural rice variations and a powerful tool for exploiting great potential of rare variants in future rice research, including population genetics and functional genomics.

Understanding Electrochemical Performance Enhancement with Quaternary NCMA Cathode Materials.

Ni-rich cathode materials show promise for use in lithium-ion batteries. However, a significant obstacle to their widespread adoption is the structural damage caused by microcracks. This research paper presents the synthesis of Ni-rich cathode materials, including LiNi0.8Co0.1Mn0.1O2 (referred to as NCM) and Li(Ni0.8Co0.1Mn0.1)0.98Al0.02O2 (referred to as NCMA), achieved through the high-temperature solid-phase method. Electrochemical (EC) testing results reveal the impressive EC performance of NCMA. NCMA exhibited a discharge capacity of 141.6 mAh g-1 and maintained a cycle retention rate of up to 74.92% after 300 cycles at a 1 C rate. In contrast, the NCM had a discharge capacity of 109.7 mAh g-1 and a cycle retention rate of 61.22%. Atomic force microscopy showed that the Derjaguin-Muller-Toporov (DMT) modulus value of NCMA exceeded that of NCM, signifying a greater mechanical strength of NCMA. Density functional theory calculations demonstrated that the addition of aluminum during the delithiation process led to the mitigation of anisotropic lattice changes and the stabilization of the NCMA structure. This improvement was attributed to the relatively stronger Al-O bonds compared to the Ni(Co, Mn)-O bonds, which reduced the formation of microcracks by enhancing NCMA's mechanical strength.

Improving the Cycle Stability of LiNiO2 through Al3+ Doping and LiAlO2 Coating.

In this study, we addressed the poor cycling and rate performance of LiNiO2, a material with ultrahigh nickel content considered a strong contender for high-energy-density lithium-ion battery cathodes. We introduced nano-Al2O3 during the lithiation process to achieve dual modified material through bulk phase element doping and in situ LiAlO2 coating. Comparison revealed notable improvements in the modified materials. In particular, LiNi0.99Al0.01O2 maintained a capacity retention rate of 73.1% after 300 cycles in a long-cycle test at 0.5C current density, outperforming the undoped material. In rate performance tests, the doped samples consistently exhibited higher discharge-specific capacities than that of the undoped counterpart. Notably, at a high current density of 5C, LiNi0.99Al0.01O2 exhibited a discharge-specific capacity of 101.75 mAh g-1. The results indicate that an appropriate amount of Al doping can effectively stabilize the layered structure of the cathode material and delay the irreversible phase transition from H2 to H3. Further, Al doping facilitates the formation of a LiAlO2 coating on the surface of the particles. This coating acts as a fast-ion conductor, enhancing the transport of lithium ions and reducing the erosion of the active material by the electrolyte.

Enhanced Cathode Performance: The Heterostructure Construction of LiCoO2@Co3O4@Li6.4La3Zr1.4Ta0.6O12.

In this study, the heterostructure cathode material LiCoO2@Co3O4@Li6.4La3Zr1.4Ta0.6O12 was prepared by coating Li6.4La3Zr1.4Ta0.6O12 on the surface of LiCoO2 through a one-step solid-phase synthesis. The morphology, structure, electrical state, and elemental contents of both pristine and modified materials were assessed through a range of characterization techniques. Theoretical calculations revealed that the LCO@LLZTO material possessed a reduced diffusion barrier compared to LiCoO2, thereby facilitating the movement of Li ions. Electrochemical tests indicated that the capacity retention rate of the modified cathode composites stood at 70.43% following 300 cycles at a 2C rate. This high rate occurred because the Li6.4La3Zr1.4Ta0.6O12 film on the surface enhanced the migration of Li+, and the spinel phase of Co3O4 had better interfacial stability to alleviate the generation of microcracks by inhibiting the phase change from the layered phase to the rock-salt phase, which considerably improved the electrochemical properties.

A centromere map based on super pan-genome highlights the structure and function of rice centromeres.

Rice (Oryza sativa) is a significant crop worldwide with a genome shaped by various evolutionary factors. Rice centromeres are crucial for chromosome segregation, and contain some unreported genes. Due to the diverse and complex centromere region, a comprehensive understanding of rice centromere structure and function at the population level is needed. We constructed a high-quality centromere map based on the rice super pan-genome consisting of a 251-accession panel comprising both cultivated and wild species of Asian and African rice. We showed that rice centromeres have diverse satellite repeat CentO, which vary across chromosomes and subpopulations, reflecting their distinct evolutionary patterns. We also revealed that long terminal repeats (LTRs), especially young Gypsy-type LTRs, are abundant in the peripheral CentO-enriched regions and drive rice centromere expansion and evolution. Furthermore, high-quality genome assembly and complete telomere-to-telomere (T2T) reference genome enable us to obtain more centromeric genome information despite mapping and cloning of centromere genes being challenging. We investigated the association between structural variations and gene expression in the rice centromere. A centromere gene, OsMAB, which positively regulates rice tiller number, was further confirmed by expression quantitative trait loci, haplotype analysis and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 methods. By revealing the new insights into the evolutionary patterns and biological roles of rice centromeres, our finding will facilitate future research on centromere biology and crop improvement.

Lung function and risk of incident dementia: A prospective cohort study of 431,834 individuals.

BACKGROUND: Whether lung function prospectively affects cognitive brain health independent of their overlapping factors remains largely unknown. This study aimed to investigate the longitudinal association between decreased lung function and cognitive brain health and to explore underlying biological and brain structural mechanisms. METHODS: This population-based cohort included 43,1834 non-demented participants with spirometry from the UK Biobank. Cox proportional hazard models were fitted to estimate the risk of incident dementia for individuals with low lung function. Mediation models were regressed to explore the underlying mechanisms driven by inflammatory markers, oxygen-carrying indices, metabolites, and brain structures. FINDINGS: During a follow-up of 3,736,181 person-years (mean follow-up 8.65 years), 5,622 participants (1.30 %) developed all-cause dementia, which consisted of 2,511 Alzheimer's dementia (AD) and 1,308 Vascular Dementia (VD) cases. Per unit decrease in lung function measure was each associated with increased risk for all-cause dementia (forced expiratory volume in 1 s [liter]: hazard ratio [HR, 95 %CI], 1.24 [1.14-1.34], P = 1.10 × 10-07; forced vital capacity [liter]: 1.16 [1.08-1.24], P = 2.04 × 10-05; peak expiratory flow [liter/min]: 1.0013 [1.0010-1.0017], P = 2.73 × 10-13). Low lung function generated similar hazard estimates for AD and VD risks. As underlying biological mechanisms, systematic inflammatory markers, oxygen-carrying indices, and specific metabolites mediated the effects of lung function on dementia risks. Besides, brain grey and white matter patterns mostly affected in dementia were substantially changed with lung function. INTERPRETATION: Life-course risk for incident dementia was modulated by individual lung function. Maintaining optimal lung function is useful for healthy aging and dementia prevention.

Daytime napping and Alzheimer's dementia: A potential bidirectional relationship.

INTRODUCTION: Daytime napping is frequently seen in older adults. The longitudinal relationship between daytime napping and cognitive aging is unknown. METHODS: Using data from 1401 participants of the Rush Memory and Aging Project, we examined the longitudinal change of daytime napping inferred objectively by actigraphy, and the association with incident Alzheimer's dementia during up to 14-year follow-up. RESULTS: Older adults tended to nap longer and more frequently with aging, while the progression of Alzheimer's dementia accelerates this change by more than doubling the annual increases in nap duration/frequency. Longer and more frequent daytime naps were associated with higher risk of Alzheimer's dementia. Interestingly, more excessive (longer or more frequent) daytime napping was correlated with worse cognition a year later, and conversely, worse cognition was correlated with more excessive naps a year later. DISCUSSION: Excessive daytime napping and Alzheimer's dementia may possess a bidirectional relationship or share common pathophysiological mechanisms.

The interleukin-enhanced binding factor 3-mediated inhibition of nitric oxide production via phosphoinositide 3-kinase/protein kinase B pathway contributes to central cardiovascular regulation in the rostral ventrolateral medulla in hypertension.

Hypertension is characterized by sympathetic hyperactivity, which is related to the overexcitation of the presympathetic neurons in the rostral ventrolateral medulla (RVLM). Nitric oxide (NO) has been reported to be a vital neuromodulator involved in central cardiovascular regulation. However, the mechanism of interleukin-enhanced binding factor 3 (ILF3) participating in blood pressure (BP) regulation is still unclear. Therefore, this study aims to clarify the role of ILF3 within the rostral ventrolateral medulla (RVLM) in regulating NO in hypertension. It was found that the expression level of ILF3 was significantly increased in the RVLM of spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats through microarray gene expression analysis, Western blot, and immunofluorescence. Overexpression of ILF3 by injecting constructed adenovirus into the RVLM increased the BP and renal sympathetic nerve activity (RSNA) of the WKY rats, significantly decreasing NO production and neuronal nitric oxide synthase (nNOS) expression. Knockdown of ILF3 in the RVLM of SHR significantly reduced BP but increased NO production and the neuronal nitric oxide synthase (nNOS) expression. Furthermore, it was found that the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was activated via Western blotting in the RVLM after overexpression of ILF3, whereas it was attenuated after knockdown of ILF3 in SHR. In addition, inhibition of PI3K by intracisternal infusion of the PI-103 attenuated the increase in Akt phosphorylation and decrease in nNOS expression and NO production caused by overexpressing ILF3, which ultimately blunted high BP induced by overexpressing ILF3. Taken together, this current study suggests that ILF3 participates in high BP via reducing NO production in the RVLM through PI3K/Akt pathway.

Genetic Risk of Alzheimer's Disease and Sleep Duration in Non-Demented Elders.

Growing evidence has suggested an association between sleep duration and Alzheimer's disease (AD), but it is unclear if sleep duration is a manifestation of the AD disease process. We studied whether genetic liability for AD predicts sleep duration using a genetic risk score (GRS) for AD (AD-GRS), in 406,536 UK Biobank participants with European ancestry and without dementia at enrollment. Higher AD-GRS score was associated with shorter sleep (b = -0.014, 95% confidence interval [CI] = -0.022 to -0.006), especially in those aged 55+. Using AD-GRS as an instrumental variable for AD diagnosis, incipient AD reduced sleep duration by 1.87 hours (95% CI = 0.96, 2.78). Short sleep duration might be an early marker of AD. ANN NEUROL 2021;89:177-181.

Volumetric Analysis of Intravoxel Incoherent Motion Diffusion-Weighted Imaging for Predicting the Response to Chemotherapy in Patients With Locally Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: We aimed to prospectively investigate intravoxel incoherent motion parameters to predict the response to chemotherapy in locally advanced non-small cell lung cancer (NSCLC) patients. METHODS: From July 2016 to March 2018, 30 advanced NSCLC patients were enrolled and underwent chest intravoxel incoherent motion-diffusion-weighted imaging at Siemens 3T magnetic resonance imaging before and at the end of the first cycle of chemotherapy. Regions of interest were drawn including the whole tumor volume to derive the apparent diffusion coefficient value, D, D*, and f, respectively. Time-dependent receiver operating characteristic curves were generated to evaluate the cutoff values of continuous variables. A Cox proportional hazards model was used to assess the independent predictors of progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves and log-rank test were generated. RESULTS: Among the 30 patients, 28 cases (93.3%) died and 2 cases (6.7%) survived till the closeout date. Univariate Cox regression analyses revealed that the significant predictors of PFS and OS were the tumor size reduction rate, the change rates of D and apparent diffusion coefficient values, and the D value before therapy (PFS: P = 0.015, hazard ratio [HR] = 2.841; P < 0.001, HR = 5.840; P = 0.044, HR = 2.457; and P = 0.027, HR = 2.715; OS: P = 0.008, HR = 2.987; P < 0.001, HR = 4.357; P = 0.006, HR = 3.313; and P = 0.013, HR = 2.941, respectively). Multivariate Cox regression analysis suggested that △D% was identified as independent predictors of both PFS and OS (P = 0.003, HR = 9.200 and P = 0.016, HR = 4.617). In addition, the cutoff value of △D% was 21.06% calculated by receiver operating characteristic curve analysis. In the Kaplan-Meier analysis, the PFS and OS were significantly greater in the group of patients with △D% larger than 21.06% (log-rank test, χ2 = 16.453, P < 0.001; χ2 = 13.952, P < 0.001). CONCLUSIONS: Intravoxel incoherent motion-diffusion-weighted imaging was preferred for predicting the prognosis of advanced NSCLC patients treated with chemotherapy. A D increase more than 21.06% at 1 month was associated with a lower rate of disease progression and death.

Pharmacological and non-pharmacological interventions to enhance sleep in mild cognitive impairment and mild Alzheimer's disease: A systematic review.

Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD dementia cases. However early intervention is needed in the course of AD at Mild Cognitive Impairment (MCI) or mild dementia stages to help prevent decline and maintain good quality of life. This systematic review aims to summarize evidence on sleep interventions in MCI and mild AD dementia. Seven databases were systematically searched for interventional studies where ≥ 75% of participants met diagnostic criteria for MCI/mild AD dementia, with a control group and validated sleep outcome measures. Studies with a majority of participants diagnosed with Moderate to Severe AD were excluded. After removal of duplicates, 22,133 references were returned in two separate searches (August 2019 and September 2020). 325 full papers were reviewed with 18 retained. Included papers reported 16 separate studies, total sample (n = 1,056), mean age 73.5 years. 13 interventions were represented: Cognitive Behavioural Therapy - Insomnia (CBT-I), A Multi-Component Group Based Therapy, A Structured Limbs Exercise Programme, Aromatherapy, Phase Locked Loop Acoustic Stimulation, Transcranial Stimulation, Suvorexant, Melatonin, Donepezil, Galantamine, Rivastigmine, Tetrahydroaminoacridine and Continuous Positive Airway Pressure (CPAP). Psychotherapeutic approaches utilising adapted CBT-I and a Structured Limbs Exercise Programme each achieved statistically significant improvements in the Pittsburgh Sleep Quality Index with one study reporting co-existent improved actigraphy variables. Suvorexant significantly increased Total Sleep Time and Sleep Efficiency whilst reducing Wake After Sleep Onset time. Transcranial Stimulation enhanced cortical slow oscillations and spindle power during daytime naps. Melatonin significantly reduced sleep latency in two small studies and sleep to wakefulness transitions in a small sample. CPAP demonstrated efficacy in participants with Obstructive Sleep Apnoea. Evidence to support other interventions was limited. Whilst new evidence is emerging, there remains a paucity of evidence for sleep interventions in MCI and mild AD highlighting a pressing need for high quality experimental studies exploring alternative sleep interventions.

Identification of dicyclohexyl phthalate as a glucocorticoid receptor antagonist by molecular docking and multiple in vitro methods.

The potential activities of phthalate esters (PAEs) that interfere with the endocrine system have been focused recently. However, information on modulating the glucocorticoid receptor (GR) of PAEs is scarce. Our aim was to evaluate the agonistic / antagonistic properties of PAEs on human GR. Luciferase reporter gene assay revealed that the tested chemicals displayed no agonistic effects but dicyclohexyl phthalate (DCHP) exerted antagonistic activity in a dose-responsive manner for GR in HeLa cells. The effects of DCHP on dexamethasone (DEX)-induced GR nuclear translocation and gene expression of glucocorticoid-responsive gene expression (G6Pase, PEPCK, FAS, GILZ and MKP-1), as well as protein expression of G6Pase and PEPCK were further examined by RT-qPCR and western blot analysis. DCHP antagonized DEX-induced GR nuclear translocation and suppressed gene expression in both mRNA and protein levels. Furthermore, the results of molecular docking and molecular dynamics simulation showed that DCHP could bind to GR and exhibited potential regulation on this target protein. Collectively, we demonstrate that DCHP may act as a GR antagonist in vitro and is considered to exert endocrine effects via human GR.

Comparative Analysis of the Extracellular Matrix Proteome across the Myotendinous Junction.

The myotendinous junction is a highly interdigitated interface designed to transfer muscle-generated force to tendon. Understanding how this interface is formed and organized, as well as identifying tendon- and muscle-specific extracellular matrix (ECM), is critical for designing effective regenerative therapies to restore functionality to damaged muscle-tendon units. However, a comparative analysis of the ECM proteome across this interface has not been conducted. The goal of this study was to resolve the distribution of ECM proteins that are uniformly expressed as well as those specific to each of the muscle, tendon, and junction tissues. The soleus muscles from 5-month-old wild-type C57BL/6 mice were harvested and dissected into the central muscle (M) away from tendon, the junction between muscle and tendon (J) and the tendon (T). Tissues were processed by either homogenizing in guanidine hydrochloride or fractionating to isolate the ECM from more soluble intracellular components and then analyzed using liquid chromatography-tandem mass spectrometry. Overall, we found that both tissue processing methods generated similar ECM profiles. Many ECM were found across the muscle-tendon unit, including type I collagen and associated fibril-regulating proteins. The ECM identified exclusively in M were primarily related to the basal lamina, whereas those specific to T and J tissue included thrombospondins and other matricellular ECM. Type XXII collagen (COL22A1) was restricted to J, and we identified COL5A3 as a potential marker of the muscle-tendon interface. Immunohistochemical analysis of key proteins confirmed the restriction of some basal lamina proteins to M, tenascin-C to T, and COL22A1 to J. COL5A3, PRELP, and POSTN were visualized in the tissue surrounding the junction, suggesting that these proteins play a role in stabilizing the interface. This comparative map provides a guide for tissue-specific ECM that can facilitate the spatial visualization of M, J, and T tissues and inform musculoskeletal regenerative therapies.

Mortality risk of loneliness in the oldest old over a 10-year follow-up.

Objective: To investigate the impact of loneliness on all-cause mortality in the oldest old population over a 10-year follow-up.Method: Participants were from the third wave of the Cambridge City over-75s Cohort (CC75C) study, a population-based longitudinal study of older people aged 75 or over. Loneliness was measured two further times. At each wave, participants were asked how often they felt lonely and the answers were divided into three levels: not lonely, slightly lonely and lonely. The relationship between loneliness and all-cause mortality was examined using Cox regression with loneliness as a time-varying predictor. The association was adjusted for socio-demographic factors, number of chronic diseases, functional ability and depression.Results: Seven hundred thirteen participants were seen at wave 3 (out of 2166 at baseline), of whom 665 had data on loneliness. The prevalence of feeling slightly lonely and lonely was 16% and 25%, respectively. Vital status was followed for a further 10 years. A total of 562 participants died during the follow-up. After adjusting for age, sex and other socio-demographic factors, loneliness was associated with a 20% increased risk of mortality (HR: 1.2, 95% CI: 1.0-1.6). The association was disappeared after further adjusting for health conditions and depression (HR: 1.0, 95% CI: 0.8-1.4). Individuals who reported being slightly lonely were not at risk of mortality.Conclusions: The association between loneliness and mortality was fully explained by health conditions, suggesting that in the very old age, health problem is the proximal risk factor for mortality.

Phthalate esters and dexamethasone synergistically activate glucocorticoid receptor.

This study was conducted to determine the endocrine-disrupting effects of phthalate esters (PAEs) on the glucocorticoid receptor (GR) signaling. Potential (anti)glucocorticoid activities of six typical PAEs including di (2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), diethyl phthalate (DEP) and dimethyl phthalate (DMP) were evaluated on human GR using cell viability assessment, reporter gene expression analysis, mRNA analysis, and molecular docking and simulation. For all tested chemicals, co-treatment of DEHP and DINP with dexamethasone (DEX) exhibited a synergistic effect on GR transactivity in the reporter assays. Such co-treatment also synergistically enhanced DEX-induced upregulation of GR mediated gene (PEPCK, FAS and MKP-1) mRNA expression in HepG2 cells and A549 cells. Molecular docking and dynamics simulations showed that hydrophobic interactions may stabilize the binding between molecules and GR. In summary, DEHP and DINP may be involved in synergistic effects via human GR, which highlight the potential endocrine-disrupting activities of PAEs as contaminants.

Three-dimensional visualization of extracellular matrix networks during murine development.

The extracellular matrix (ECM) plays a crucial role in embryogenesis, serving both as a substrate to which cells attach and as an active regulator of cell behavior. However, little is known about the spatiotemporal expression patterns and 3D structure of ECM proteins during embryonic development. The lack of suitable methods to visualize the embryonic ECM is largely responsible for this gap, posing a major technical challenge for biologists and tissue engineers. Here, we describe a method of viewing the 3D organization of the ECM using a polyacrylamide-based hydrogel to provide a 3D framework within developing murine embryos. After removal of soluble proteins using sodium dodecyl sulfate, confocal microscopy was used to visualize the 3D distribution of independent ECM networks in multiple developing tissues, including the forelimb, eye, and spinal cord. Comparative analysis of E12.5 and E14.5 autopods revealed proteoglycan-rich fibrils maintain connections between the epidermis and the underlying tendon and cartilage, indicating a role for the ECM during musculoskeletal assembly and demonstrating that our method can be a powerful tool for defining the spatiotemporal distribution of the ECM during embryogenesis.

Analysis of misdiagnosed cases of hemorrhagic fever with renal syndrome in children: two cases and literature review.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is an acute disease caused by hantavirus infection and is clinically characterized by fever, various hemorrhagic manifestations and transient renal and hepatic dysfunctions. Although various cases of HFRS have been reported, cases in children have rarely been described. Herein, we report two atypical cases of HFRS in children without distinctive manifestations and typical disease clinically progresses. CASE PRESENTATION: Patient 1 was a 11-year-old girl who attended our clinic for fever accompanying with acute renal failure, proteinuria and decreased level of complement 3 (C3) and thrombocytopenia without any hemorrhagic manifestations, acute glomerulonephritis was suspected first, especially lupus nephritis. Patient 2 was misdiagnosed as encephalitis at local hospital because of fever and headache for 4 days. With elevated liver transaminases, proteinuria and normal cerebrospinal fluid examination, HFRS was taken into consideration. Both of the two cases were supported and confirmed by serological test for Hantavirus. CONCLUSIONS: Clinical manifestations of HFRS in children often presented atypically and were milder than adults. Febrile disease accompanying with thrombocytopenia may lead to the suspected diagnosis of HFRS.