Hemodiafiltration with endogenous reinfusion for uremic toxin removal in patients undergoing maintenance hemodialysis: a pilot study.

OBJECTIVE: To delineate the efficacy and safety profile of hemodiafiltration with endogenous reinfusion (HFR) for uremic toxin removal in patients undergoing maintenance hemodialysis (MHD). METHODS: Patients who have been on MHD for a period of at least 3 months were enrolled. Each subject underwent one HFR and one hemodiafiltration (HDF) treatment. Blood samples were collected before and after a single HFR or HDF treatment to test uremic toxin levels and to calculate clearance rate. The primary efficacy endpoint was to compare uremic toxin levels of indoxyl sulfate (IS), λ-free light chains (λFLC), and ß2-microglobulin (ß2-MG) before and after HFR treatment. Secondary efficacy endpoints was to compare the levels of urea, interleukin-6 (IL-6), P-cresol, chitinase-3-like protein 1 (YKL-40), leptin (LEP), hippuric acid (HPA), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), fibroblast growth factor 23 (FGF23) before and after HFR treatment. The study also undertook a comparative analysis of uremic toxin clearance between a single HFR and HDF treatment. Meanwhile, the lever of serum albumin and branched-chain amino acids before and after a single HFR or HDF treatment were compared. In terms of safety, the study was meticulous in recording vital signs and the incidence of adverse events throughout its duration. RESULTS: The study enrolled 20 patients. After a single HFR treatment, levels of IS, λFLC, ß2-MG, IL-6, P-cresol, YKL-40, LEP, HPA, TMAO, ADMA, TNF-α, and FGF23 significantly decreased (p < 0.001 for all). The clearance rates of λFLC, ß2-MG, IL-6, LEP, and TNF-α were significantly higher in HFR compared to HDF (p values: 0.036, 0.042, 0.041, 0.019, and 0.036, respectively). Compared with pre-HFR and post-HFR treatment, levels of serum albumin, valine, and isoleucine showed no significant difference (p > 0.05), while post-HDF, levels of serum albumin significantly decreased (p = 0.000). CONCLUSION: HFR treatment effectively eliminates uremic toxins from the bloodstream of patients undergoing MHD, especially protein-bound toxins and large middle-molecule toxins. Additionally, it retains essential physiological compounds like albumin and branched-chain amino acids, underscoring its commendable safety profile.

Exploring the link between brain topological resilience and cognitive performance in the context of aging and vascular risk factors: A cross-ethnicity population-based study.

Brain aging is typically associated with a significant decline in cognitive performance. Vascular risk factors (VRF) and subsequent atherosclerosis (AS) play a major role in this process. Brain resilience reflects the brain's ability to withstand external perturbations, but the relationship of brain resilience with cognition during the aging process remains unclear. Here, we investigated how brain topological resilience (BTR) is associated with cognitive performance in the face of aging and vascular risk factors. We used data from two cross-ethnicity community cohorts, PolyvasculaR Evaluation for Cognitive Impairment and Vascular Events (PRECISE, n = 2220) and Sydney Memory and Ageing Study (MAS, n = 246). We conducted an attack simulation on brain structural networks based on k-shell decomposition and node degree centrality. BTR was defined based on changes in the size of the largest subgroup of the network during the simulation process. Subsequently, we explored the negative correlations of BTR with age, VRF, and AS, and its positive correlation with cognitive performance. Furthermore, using structural equation modeling (SEM), we constructed path models to analyze the directional dependencies among these variables, demonstrating that aging, AS, and VRF affect cognition by disrupting BTR. Our results also indicated the specificity of this metric, independent of brain volume. Overall, these findings underscore the supportive role of BTR on cognition during aging and highlight its potential application as an imaging marker for objective assessment of brain cognitive performance.

Triptolide alleviates cerebral ischemia/reperfusion injury via regulating the Fractalkine/CX3CR1 signaling pathway.

PURPOSE: To evaluate the potential efficacy of Triptolide (TP) on cerebral ischemia/reperfusion injury (CIRI) and to uncover the underlying mechanism through which TP regulates CIRI. METHODS: We constructed a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to simulate CIRI, and established a lipopolysaccharide (LPS)-stimulated BV-2 cell model to mimic the inflammatory state during CIRI. The neurological deficits score (NS) of mice were measured for assessment of neurologic functions. Both the severity of cerebral infarction and the apoptosis level in mouse brain tissues or cells were respectively evaluated using corresponding techniques. The expression levels of Ionized calcium binding adapter molecule 1 (IBA-1), Inductible Nitric Oxide Synthase (iNOS), Arginase 1 (Arg-1), Tumor necrosis factor-α (TNF-α), Interleukin 1ß (IL-1ß), Cysteine histoproteinase S (CTSS), Fractalkine, chemokine C-X3-C motif receptor 1 (CX3CR1), BCL-2-associated X protein (BAX), and antiapoptotic proteins (Bcl-2) were detected using immunofluorescence, qRT-PCR as well as Western blot, respectively. RESULTS: Relative to the Sham group, treatment with TP attenuated the increased NS, infarct area and apoptosis levels observed in MCAO/R mice. Upregulated expression levels of IBA-1, iNOS, Arg-1, TNF-α and IL-1ß were found in MCAO/R mice, while TP suppressed iNOS, TNF-α and IL-1ß expression, and enhanced Arg-1 expression in both MCAO/R mice and LPS-stimulated BV-2 cells. Besides, TP inhibited the CTSS/Fractalkine/CX3CR1 pathway activation in both MCAO/R mice and LPS-induced BV-2 cells, while overexpression of CTSS reversed such effect. Co-culturing HT-22 cells with TP+LPS-treated BV-2 cells led to enhanced cell viability and decreased apoptosis levels. However, overexpression of CTSS further aggravated HT-22 cell injury. CONCLUSION: TP inhibits not only microglia polarization towards the M1 phenotype by suppressing the CTSS/Fractalkine/CX3CR1 pathway activation, but also HT-22 apoptosis by crosstalk with BV-2 cells, thereby ameliorating CIRI. These findings reveal a novel mechanism of TP in improving CIRI, and offer potential implications for addressing the preventive and therapeutic strategies of CIRI.

AnDREB5.1, a A5 group DREB gene from desert shrub Ammopiptanthus nanus, confers osmotic and cold stress tolerances in transgenic tobacco.

The Dehydration-Responsive Element Binding (DREB) subfamily of transcription factors plays crucial roles in plant abiotic stress response. Ammopiptanthus nanus (A. nanus) is an eremophyte exhibiting remarkable tolerance to environmental stress and DREB proteins may contribute to its tolerance to water deficit and low-temperature stress. In the present study, an A. nanus DREB A5 group transcription factor gene, AnDREB5.1, was isolated and characterized in terms of structure and function in abiotic stress tolerance. AnDREB5.1 protein is distributed in the nucleus, possesses transactivation capacity, and is capable of binding to DRE core cis-acting element. The transcription of AnDREB5.1 was induced under osmotic and cold stress. Tobacco seedlings overexpressing AnDREB5.1 displayed higher tolerance to cold stress, osmotic stress, and oxidative stress compared to wild-type tobacco (WT). Under osmotic and cold stress, overexpression of AnDREB5.1 increased antioxidant enzyme activity in tobacco leaves, inhibiting excessive elevation of ROS levels. Transcriptome sequencing analysis showed that overexpression of AnDREB5.1 raised the tolerance of transgenic tobacco seedlings to abiotic stress by regulating multiple genes, including antioxidant enzymes, transcription factors, and stress-tolerant related functional genes like NtCOR413 and NtLEA14. This study provides new evidence for understanding the potential roles of the DREB A5 subgroup members in plants.

The miR184-3p targets neuron-specific ecdysone inducible protein 78 to promote rice black streaked dwarf virus propagation in its planthopper vector.

BACKGROUND: MicroRNAs (miRNAs) are non-coding RNAs that play a pivotal role in antiviral infection. The miR184-3p has been identified to promote rice black streaked dwarf virus (RBSDV) infection in vector Laodelphax striatellus, whether it targets other genes of L. striatellus to modulate RBSDV propagation remains unknown. RESULTS: We first analyzed the expression profiles of miR184-3p and its role in regulating RBSDV infection in L. striatellus. Then the candidate genes expression of miR184-3p were systemically analyzed with gain and loss function of miR184-3p, and the interaction of candidate gene, ecdysone inducible protein 78 (Eip78) with miR184-3p was verified by dual luciferase reporter assay. We found Eip78 is evolutionary conserved among agricultural pests and predominantly expressed in the central nervous system (CNS) of L. striatellus. Knockdown of Eip78 effectively increased RBSDV propagation and transmission. Blockade with Eip78 antibody or injection with Eip78 protein could significantly regulate RBSDV infection. Further analysis revealed that knockdown of Eip78 specifically suppresses RBSDV infection in the head part but not in the body part of L. striatellus. Besides, knockdown of ecdysone receptor (EcR) notably restricted Eip78 expression and increased RBSDV accumulation in L. striatellus. CONCLUSIONS: Taken together, we identified a novel target gene of miR184-3p, Eip78, a member of the ecdysone signaling pathway, and revealed the anti-RBSDV role of Eip78 in the CNS of L. striatellus. These results shed light on the interaction mechanisms of miRNAs, virus and ecdysone signaling pathway in insect vector. © 2024 Society of Chemical Industry.

AmDHN4, a winter accumulated SKn-type dehydrin from Ammopiptanthus mongolicus, and regulated by AmWRKY45, enhances the tolerance of Arabidopsis to low temperature and osmotic stress.

Ammopiptanthus mongolicus, a rare temperate evergreen broadleaf shrub, exhibits remarkable tolerance to low temperature and drought stress in winter. Late embryogenesis abundant (LEA) proteins, a kind of hydrophilic protein with a protective function, play significant roles in enhancing plant tolerance to abiotic stress. In this present study, we analyzed the evolution and expression of LEA genes in A. mongolicus, and investigated the function and regulatory mechanism of dehydrin under abiotic stresses. Evolutionary analysis revealed that 14 AmLEA genes underwent tandem duplication events, and 36 AmLEA genes underwent segmental duplication events Notably, an expansion in SKn-type dehydrins was observed. Expression analysis showed that AmDHN4, a SKn-type dehydrin, was up-regulated in winter and under low temperature and osmotic stresses. Functional analysis showcased that the heterologous expression of the AmDHN4 enhanced the tolerance of yeast and tobacco to low temperature stress. Additionally, the overexpression of AmDHN4 significantly improved the tolerance of transgenic Arabidopsis to low temperature, drought, and osmotic stress. Further investigations identified AmWRKY45, a downstream transcription factor in the jasmonic acid signaling pathway, binding to the AmDHN4 promoter and positively regulating its expression. In summary, these findings contribute to a deeper understanding of the functional and regulatory mechanisms of dehydrin.

Onset of acute severe autoimmune hepatitis after severe acute respiratory syndrome coronavirus 2 infection: a case report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can trigger autoimmune inflammation in the liver, leading to acute autoimmune hepatitis (AIH). We herein report a case involving a 39-year-old woman with a 23-day history of yellow skin and urine. Using the revised original scoring system of the International AIH Group, we definitively diagnosed the patient with acute severe AIH (AS-AIH). She began treatment with 80 mg/day intravenous methylprednisolone, which was gradually reduced and followed by eventual transition to oral methylprednisolone. The patient finally achieved a biochemical response after 30 days of therapy, and liver transplantation was avoided. Clinicians should be aware that the onset of AS-AIH after SARS-CoV-2 infection differs from the onset of conventional AIH with respect to its clinical and pathological features. Early diagnosis and timely glucocorticoid treatment are crucial in improving outcomes.

A Novel Dual-Fc Bispecific Antibody with Enhanced Fc Effector Function.

Bispecific antibodies (BsAbs) are undergoing continued development for applications in oncology and autoimmune diseases. While increasing activity by having more than one targeting arm, most BsAb engineering employs single Fc engagement as monoclonal antibodies. Here, we designed a novel immunoglobulin gamma-1 (IgG1)-derived dual-Fc BsAb containing two Fc regions and two distinct asymmetric antigen binding arms comprising a Fab arm and another VHH domain. In conjunction with the knob-into-hole technology, dual-Fc BsAbs could be produced with a high yield and good stability. We explore how Fc engineering effects on dual-Fc constructs could boost the desired therapeutic efficacy. This new format enabled simultaneous bispecific binding to corresponding antigens. Furthermore, compared to the one-Fc control molecules, dual-Fc BsAbs were shown to increase the avidity-based binding to FcγRs to result in higher ADCC and ADCP activities by potent avidity via binding to two antigens and Fc receptors. Overall, this novel BsAb format with enhanced effector functionalities provides a new option for antibody-based immunotherapy.

2-Hydroxy-5-nitro-3-(trifluoromethyl)pyridine as a Novel Matrix for Enhanced MALDI Imaging of Tissue Metabolites.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which is a label-free imaging technique, determines the spatial distribution and relative abundance of versatile endogenous metabolites in tissues. Meanwhile, matrix selection is generally regarded as a pivotal step in MALDI tissue imaging. This study presents the first report of a novel MALDI matrix, 2-hydroxy-5-nitro-3-(trifluoromethyl)pyridine (HNTP), for the in situ detection and imaging of endogenous metabolites in rat liver and brain tissues by MALDI-MS in positive-ion mode. The HNTP matrix exhibits excellent characteristics, including strong ultraviolet absorption, µm-scale matrix crystals, high chemical stability, low background ion interference, and high metabolite ionization efficiency. Notably, the HNTP matrix also shows superior detection capabilities, successfully showing 185 detectable metabolites in rat liver tissue sections. This outperforms the commonly used matrices of 2,5-dihydroxybenzoic acid and 2-mercaptobenzothiazole, which detect 145 and 120 metabolites from the rat liver, respectively. Furthermore, a total of 152 metabolites are effectively detected and imaged in rat brain tissue using the HNTP matrix, and the spatial distribution of these compounds clearly shows the heterogeneity of the rat brain. The results demonstrate that HNTP is a new and powerful positive-ion mode matrix to enhance the analysis of metabolites in biological tissues by MALDI-MSI.

Breviscapine alleviates myocardial ischemia-reperfusion injury in diabetes rats.

PURPOSE: To investigate the protective effect of breviscapine on myocardial ischemia-reperfusion injury (MIRI) in diabetes rats. METHODS: Forty rats were divided into control, diabetes, MIRI of diabetes, and treatment groups. The MIRI of diabetes model was established in the latter two groups. Then, the treatment group was treated with 100 mg/kg breviscapine by intraperitoneal injection for 14 consecutive days. RESULTS: After treatment, compared with MIRI of diabetes group, in treatment group the serum fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance, and glycosylated hemoglobin levels decreased, the serum total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels decreased, the serum high-density lipoprotein cholesterol level increased, the heart rate decreased, the mean arterial pressure, left ventricular ejection fraction, and fractional shortening increased, the serum cardiac troponin I, and creatine kinase-MB levels decreased, the myocardial tumor necrosis factor α and interleukin-6 levels decreased, the myocardial superoxide dismutase level increased, and the myocardial malondialdehyde level decreased (all P < 0.05). CONCLUSIONS: For treating MIRI of diabetes in rats, the breviscapine can reduce the blood glucose and lipid levels, improve the cardiac function, reduce the myocardial injury, and decrease the inflammatory response and oxidative stress, thus exerting the alleviating effect.

Disrupted pattern of rich-club organization in structural brain network from prediabetes to diabetes: A population-based study.

The network nature of the brain is gradually becoming a consensus in the neuroscience field. A set of highly connected regions in the brain network called "rich-club" are crucial high efficiency communication hubs in the brain. The abnormal rich-club organization can reflect underlying abnormal brain function and metabolism, which receives increasing attention. Diabetes is one of the risk factors for neurological diseases, and most individuals with prediabetes will develop overt diabetes within their lifetime. However, the gradual impact of hyperglycemia on brain structures, including rich-club organization, remains unclear. We hypothesized that the brain follows a special disrupted pattern of rich-club organization in prediabetes and diabetes. We used cross-sectional baseline data from the population-based PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study, which included 2218 participants with a mean age of 61.3 ± 6.6 years and 54.1% females comprising 1205 prediabetes, 504 diabetes, and 509 normal control subjects. The rich-club organization and network properties of the structural networks derived from diffusion tensor imaging data were investigated using a graph theory approach. Linear mixed models were used to assess associations between rich-club organization disruptions and the subjects' glucose status. Based on the graphical analysis methods, we observed the disrupted pattern of rich-club organization was from peripheral regions mainly located in frontal areas to rich-club regions mainly located in subcortical areas from prediabetes to diabetes. The rich-club organization disruptions were associated with elevated glucose levels. These findings provided more details of the process by which hyperglycemia affects the brain, contributing to a better understanding of the potential neurological consequences. Furthermore, the disrupted pattern observed in rich-club organization may serve as a potential neuroimaging marker for early detection and monitoring of neurological disorders in individuals with prediabetes or diabetes.

Characterization of NAC Gene Family in Ammopiptanthus mongolicus and Functional Analysis of AmNAC24, an Osmotic and Cold-Stress-Induced NAC Gene.

The NAC family of transcription factors (TFs) is recognized as a significant group within the plant kingdom, contributing crucially to managing growth and development processes in plants, as well as to their response and adaptation to various environmental stressors. Ammopiptanthus mongolicus, a temperate evergreen shrub renowned for its remarkable resilience to low temperatures and drought stress, presents an ideal subject for investigating the potential involvement of NAC TFs in stress response mechanisms. Here, the structure, evolution, and expression profiles of NAC family TFs were analyzed systematically, and a cold and osmotic stress-induced member, AmNAC24, was selected and functionally characterized. A total of 86 NAC genes were identified in A. mongolicus, and these were divided into 15 groups. Up to 48 and 8 NAC genes were generated by segmental duplication and tandem duplication, respectively, indicating that segmental duplication is a predominant mechanism in the expansion of the NAC gene family in A. mongolicus. A considerable amount of NAC genes, including AmNAC24, exhibited upregulation in response to cold and osmotic stress. This observation is in line with the detection of numerous cis-acting elements linked to abiotic stress response in the promoters of A. mongolicus NAC genes. Subcellular localization revealed the nuclear residence of the AmNAC24 protein, coupled with demonstrable transcriptional activation activity. AmNAC24 overexpression enhanced the tolerance of cold and osmotic stresses in Arabidopsis thaliana, possibly by maintaining ROS homeostasis. The present study provided essential data for understanding the biological functions of NAC TFs in plants.

Chemical and Transcriptomic Analyses of Leaf Cuticular Wax Metabolism in Ammopiptanthus mongolicus under Osmotic Stress.

Plant cuticular wax forms a hydrophobic structure in the cuticle layer covering epidermis as the first barrier between plants and environments. Ammopiptanthus mongolicus, a leguminous desert shrub, exhibits high tolerances to multiple abiotic stress. The physiological, chemical, and transcriptomic analyses of epidermal permeability, cuticular wax metabolism and related gene expression profiles under osmotic stress in A. mongolicus leaves were performed. Physiological analyses revealed decreased leaf epidermal permeability under osmotic stress. Chemical analyses revealed saturated straight-chain alkanes as major components of leaf cuticular wax, and under osmotic stress, the contents of total wax and multiple alkane components significantly increased. Transcriptome analyses revealed the up-regulation of genes involved in biosynthesis of very-long-chain fatty acids and alkanes and wax transportation under osmotic stress. Weighted gene co-expression network analysis identified 17 modules and 6 hub genes related to wax accumulation, including 5 enzyme genes coding KCS, KCR, WAX2, FAR, and LACS, and an ABCG transporter gene. Our findings indicated that the leaf epidermal permeability of A. mongolicus decreased under osmotic stress to inhibit water loss via regulating the expression of wax-related enzyme and transporter genes, further promoting cuticular wax accumulation. This study provided new evidence for understanding the roles of cuticle lipids in abiotic stress tolerance of desert plants.

An improved prediction model for COD measurements using UV-Vis spectroscopy.

In the 21st century, although water quality has been improved in the last two decades, water pollution by organic contaminants has remained a non-negligible issue in China, so Chemical-Oxygen Demand (abbreviated as COD, unit: mg L-1) is often used as the main index to measure the degree of surface water pollution. UV-Vis spectroscopy, as a sensitive and rapid analytical technique, is a green detection technology suitable for automatic online COD detection equipment. However, due to the complex composition of surface water, the interference degree of the UV-Vis spectrum caused by turbidity is strongly correlated with the size, type and color of particulate matter in the solution, which results in noise sensitivity and poor generalization of the current detection model. Therefore, the main purpose of this research is to improve the traditional detection model performance by using deep learning and a spectrum preprocessing algorithm. Firstly, we used an improved noise filter based on discrete wavelet transforms to solve the noise sensitivity. Secondly, we proposed a novel COD detection network to address poor generalization. Thirdly, we collected a total of 2259 water samples' UV-Vis absorption spectra and corresponding COD as a dataset. Then, we pipelined the improved noise removal algorithm and proposed COD detection network, as a complete COD prediction model. Finally, the experiment on the dataset shows that the COD prediction model has a good performance in terms of both noise tolerance and accuracy.

A convolutional neural network-based method for the generation of super-resolution 3D models from clinical CT images.

BACKGROUND AND OBJECTIVE: The accurate evaluation of bone mechanical properties is essential for predicting fracture risk based on clinical computed tomography (CT) images. However, blurring and noise in clinical CT images can compromise the accuracy of these predictions, leading to incorrect diagnoses. Although previous studies have explored enhancing trabecular bone CT images to super-resolution (SR), none of these studies have examined the possibility of using clinical CT images from different instruments, typically of lower resolution, as a basis for analysis. Additionally, previous studies rely on 2D SR images, which may not be sufficient for accurate mechanical property evaluation, due to the complex nature of the 3D trabecular bone structures. The objective of this study was to address these limitations. METHODS: A workflow was developed that utilizes convolutional neural networks to generate SR 3D models across different clinical CT instruments. The morphological and finite-element-derived mechanical properties of these SR models were compared with ground truth models obtained from micro-CT scans. RESULTS: A significant improvement in analysis accuracy was demonstrated, where the new SR models increased the accuracy by up to 700 % compared with the low-resolution data, i.e. clinical CT images. Additionally, we found that the mixture of different CT image datasets may improve the SR model performance. CONCLUSIONS: SR images, generated by convolutional neural networks, outperformed clinical CT images in the determination of morphological and mechanical properties. The developed workflow could be implemented for fracture risk prediction, potentially leading to improved diagnoses and subsequent clinical decision making.

Integration of human organoids single-cell transcriptomic profiles and human genetics repurposes critical cell type-specific drug targets for severe COVID-19.

Human organoids recapitulate the cell type diversity and function of their primary organs holding tremendous potentials for basic and translational research. Advances in single-cell RNA sequencing (scRNA-seq) technology and genome-wide association study (GWAS) have accelerated the biological and therapeutic interpretation of trait-relevant cell types or states. Here, we constructed a computational framework to integrate atlas-level organoid scRNA-seq data, GWAS summary statistics, expression quantitative trait loci, and gene-drug interaction data for distinguishing critical cell populations and drug targets relevant to coronavirus disease 2019 (COVID-19) severity. We found that 39 cell types across eight kinds of organoids were significantly associated with COVID-19 outcomes. Notably, subset of lung mesenchymal stem cells increased proximity with fibroblasts predisposed to repair COVID-19-damaged lung tissue. Brain endothelial cell subset exhibited significant associations with severe COVID-19, and this cell subset showed a notable increase in cell-to-cell interactions with other brain cell types, including microglia. We repurposed 33 druggable genes, including IFNAR2, TYK2, and VIPR2, and their interacting drugs for COVID-19 in a cell-type-specific manner. Overall, our results showcase that host genetic determinants have cellular-specific contribution to COVID-19 severity, and identification of cell type-specific drug targets may facilitate to develop effective therapeutics for treating severe COVID-19 and its complications.

The miR-184-3p promotes rice black-streaked dwarf virus infection by suppressing Ken in Laodelphax striatellus (Fallén).

BACKGROUND: MicroRNAs (miRNAs) play a key role in various biological processes by influencing the translation of target messenger RNAs (mRNAs) through post-transcriptional regulation. The miR-184-3p has been identified as an abundant conserved miRNA in insects. However, less is known about its functions in insect-plant virus interactions. RESULTS: The function of miR-184-3p in regulation of plant viral infection in insects was investigated using a rice black-streaked dwarf virus (RBSDV) and Laodelphax striatellus (Fallén) interaction system. We found that the expression of miR-184-3p increased in L. striatellus after RBSDV infection. Injection of miR-184-3p mimics increased RBSDV accumulation, while treatment with miR-184-3p antagomirs inhibits the viral accumulation in L. striatellus. Ken, a zinc finger protein, was identified as a target of miR-184-3p. Knockdown of Ken increased the virus accumulation and promoted RBSDV transmission by L. striatellus. CONCLUSION: This study demonstrates that RBSDV infection induces the expression of miR-184-3p in its insect vector L. striatellus. The miR-184-3p targets Ken to promote RBSDV accumulation and transmission. These findings provide a new insight into the function of the miRNAs in regulating plant viral infection in its insect vector. © 2023 Society of Chemical Industry.

Hydroxyapatite particle shape affects screw attachment in cancellous bone when augmented with hydroxyapatite-containing hydrogels.

Screw-bone construct failures are a true challenge in orthopaedic implant fixation, particularly in poor quality bone. Whilst augmentation with bone cement can improve the primary stability of screws, there are cements, e.g. PMMA, that may impede blood flow and nutrients and hamper bone remodelling. In this study, soft, non-setting biomaterials based on Hyalectin gels and hydroxyapatite (HA) particles with different morphological parameters were evaluated as potential augmentation materials, using a lapine ex vivo bone model. The pull-out force, stiffness, and work to fracture were considered in evaluating screw attachment. The pull-out force of constructs reinforced with Hyalectin containing irregularly shaped nano-HA and spherically shaped micro-HA particles were found to be significantly higher than the control group (no augmentation material). The pull-out stiffness increased for the micro-HA particles and the work to fracture increased for the irregular nano-HA particles. However, there were no significant augmentation effect found for the spherical shaped nano-HA particles. In conclusion, injectable Hyalectin gel loaded with hydroxyapatite particles was found to have a potentially positive effect on the primary stability of screws in trabecular bone, depending on the HA particle shape and size.

Effects of brain atrophy and altered functional connectivity on poststroke cognitive impairment.

BACKGROUND AND PURPOSE: Brain atrophy and disrupted functional connectivity are often present in patients with poststroke cognitive impairment (PSCI). This study aimed to explore the relationship between remote brain atrophy, connectional diaschisis and cognitive impairment in ischemic stroke patients to provide valuable information about the mechanisms underlying cognitive function recovery. METHODS: Forty first-time stroke patients with basal ganglia infarcts and twenty-nine age-matched healthy people were enrolled. All participants underwent T1-weighted and functional MRI scans, comprehensive cognitive function assessments at baseline, and 3-month follow-up. Brain volumes were calculated, and the atrophic regions were regarded as regions of interest in seed-based functional connectivity analyses. Pearson correlation analysis was used to explore the relationships among cognitive performance, brain atrophy, and functional connectivity alterations. RESULTS: Compared with healthy participants, stroke patients had worse cognitive performance at baseline and the 3-month follow-up. Worse cognitive performance was associated with smaller bilateral thalamus, left hippocampus, and left amygdala volumes, as well as lower functional connectivity between the left thalamus and the left medial superior frontal gyrus, between the right thalamus and the left median cingulate and paracingulate gyri, between the right hippocampus and the left medial superior frontal gyrus, and between the left amygdala and the right dorsolateral superior frontal gyrus. CONCLUSIONS: In patients with basal ganglia infarction, connectional diaschisis between remote brain atrophy and the prefrontal lobe plays a significant role in PSCI. This finding provides new scientific evidence for understanding the mechanisms of PSCI and indicates that the prefrontal lobe may be a target to improve cognitive function after stroke.