HIV infection increases the risk of inflammatory bowel disease: a systematic review and meta-analysis.

OBJECTIVE: In order to synthesize available results regarding human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD), we conducted a systematic review and meta-analysis to provide quantitative estimates of associated risk. METHODS: A systematic search of four scientific databases, PubMed, the Cochrane Library, EMBASE, and Scopus, was performed. The overall odds ratio (OR) with the corresponding 95% CI was calculated via a random effects model. Sensitivity analyses and tests for publication bias were then performed. RESULTS: Of the 3046 articles retrieved, seven studies with a cumulative sample size greater than 57,000,000 were included in our analysis. A subsequent meta-analysis based on a random effects model (heterogeneity test, I2 = 99.9) revealed an association between HIV infection and IBD: OR = 2.68 (95% CI: 1.17, 6.13). The funnel plot of this meta-analysis was asymmetric (Egger's test: P = 0.01), and significant publication bias was found. Sensitivity analysis of the 3 dimensions revealed that the results of this meta-analysis were relatively stable. CONCLUSIONS: A significant correlation may exist between HIV infection and intestinal disease, and more large-scale studies are needed to draw firm conclusions. It is recommended that HIV patients be screened for intestinal diseases.

Development and validation of a nomogram for oral mucosal membrane pressure injuries in ICU patients: A prospective cohort study.

AIMS: Establishing a nomogram to estimate the probability of oral mucosal membrane pressure injury of endotracheal tube-intubated hospitalized patients in intensive care unit. DESIGN: Multicentre prospective cohort study. METHODS: Using Lasso regression and COX regression, variable selection was performed on demographic, clinical and laboratory data of 1037 ICU endotracheal tube-intubated hospitalized patients from West China Hospital, to construct a nomogram. External validation was conducted on 484 ICU endotracheal tube-intubated patients from People's Hospital of Zhongjiang County. RESULTS: Among 38 potential predictors, five variables emerged as independent predictors, integrated into the nomogram: administration of antibiotics, nutritional therapy duration, agitation, hypotension and albumin levels. CONCLUSIONS: We established a nomogram based on the hospital characteristics of ICU endotracheal tube-intubated patients, aiding in the prediction of the occurrence of oral mucosal membrane pressure injury. REPORTING METHOD: The study followed TRIPOD guidelines. RELEVANCE TO CLINICAL PRACTICE: The nomogram we developed can assist clinical worker in better identifying at-risk patients and risk factors. It enables the implementation of evidence-based nursing interventions in care to prevent the development of oral mucosal membrane pressure injury. TRIAL REGISTRATION: The study has been registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn) under registration number ChiCTR2200056615.

Factors associated with moral sensitivity among nurses in adult intensive care units: A cross-sectional study in China.

BACKGROUND: Moral sensitivity may play a role in dealing with ethical issues in ICUs. However, the moral sensitivity of adult ICU nurses in China and its predictors have not been well investigated. AIMS: To analyse the moral sensitivity of intensive care unit (ICU) nurses and its predictors. STUDY DESIGN: A cross-sectional study through convenience sampling was conducted in the ICUs of five hospitals in China between November and December 2022. A total of 331 ICU nurses were recruited. Data were obtained using a self-developed socio-demographic characteristic questionnaire, the Moral Sensitivity Questionnaire, the Jefferson Scale of Empathy-Health Professionals and the Organizational Climate Scale for Nursing. The participating institutions received a link to the tools used for online data collection, which they then forwarded to nursing staff. RESULTS: The valid response rate was 96.98% (n = 321). The total mean moral sensitivity score of nurses was 43.04 ± 5.95. The mean scores for empathic ability and organizational climate for nursing were 91.97 ± 17.88 and 101.28 ± 14.77, respectively. Regression analyses revealed that the primary factors associated with moral sensitivity among critical care nurses included work tenure (p < .05), empathic ability (p < .001) and organizational climate (p < .001). CONCLUSIONS: High levels of moral sensitivity were found in critical care nurses in China. Work tenure, empathic ability and organizational climate were significant predictors of moral sensitivity in critical care nurses. RELEVANCE TO CLINICAL PRACTICE: To enhance the ethical sensitivity of ICU nurses, we suggest to strengthen the training of novice nurses so that they can better face the moral dilemma in clinical practice. In addition, organizational managers should also take measures to create a positive and harmonious working atmosphere, promote the application of moral knowledge in nursing practice and enhance their moral sensitivity.

Identification of mitochondrial related signature associated with immune microenvironment in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease. Mitochondrial dysfunction and immune responses are important factors in the pathogenesis of AD, but their crosstalk in AD has not been studied. In this study, the independent role and interaction of mitochondria-related genes and immune cell infiltration in AD were investigated using bioinformatics methods. METHODS: The datasets of AD were obtained from NCBI Gene Expression Omnibus (GEO), and the data of mitochondrial genes was from MitoCarta3.0 database. Subsequently, differential expression genes (DEGs) screening and GSEA functional enrichment analysis were performed. The intersection of DEGs and mitochondrial related genes was used to obtain MitoDEGs. The MitoDEGs most relevant to AD were determined by Least absolute shrinkage and selection operator and multiple support vector machine recursive feature elimination, as well as protein-protein interactions (PPI) network and random forest. The infiltration of 28 kinds of immune cells in AD was analyzed by ssGSEA, and the relationship between hub MitoDEGs and the proportion of immune infiltration was studied. The expression levels of hub MitoDEGs were verified in cell models and AD mice, and the role of OPA1 in mitochondrial damage and neuronal apoptosis was investigated. RESULTS: The functions and pathways of DEGs were significantly enriched in AD, including immune response activation, IL1R pathway, mitochondrial metabolism, oxidative damage response and electron transport chain-oxphos system in mitochondria. Hub MitoDEGs closely related to AD were obtained based on PPI network, random forest and two machine learning algorithms. Five hub MitoDEGs associated with neurological disorders were identified by biological function examination. The hub MitoDEGs were found to be correlated with memory B cell, effector memory CD8 T cell, activated dendritic cell, natural killer T cell, type 17 T helper cell, Neutrophil, MDSC, plasmacytoid dendritic cell. These genes can also be used to predict the risk of AD and have good diagnostic efficacy. In addition, the mRNA expression levels of BDH1, TRAP1, OPA1, DLD in cell models and AD mice were consistent with the results of bioinformatics analysis, and expression levels of SPG7 showed a downward trend. Meanwhile, OPA1 overexpression alleviated mitochondrial damage and neuronal apoptosis induced by Aß1-42. CONCLUSIONS: Five potential hub MitoDEGs most associated with AD were identified. Their interaction with immune microenvironment may play a crucial role in the occurrence and prognosis of AD, which provides a new insight for studying the potential pathogenesis of AD and exploring new targets.

Immobilization of Actinobacillus succinogenes on nano- and micro-fiber membranes for efficient and robust production of succinic acid.

This work aimed to study the efficiency of nano- and micro- fiber membranes in immobilizing Actinobacillus succinogenes CCTCC M2012036 for succinic acid production. Among the four kinds of electrospun nanofiber membranes of cellulose acetate, chitosan, poly(vinyl alcohol) (PVA) and chitosan-PVA, the cellulose acetate nanofiber membrane-immobilized cells performed the best with a succinic acid concentration and yield to be 27.3 ± 3.5 g/L and 70.9 ± 5.8%. The cell-immobilized viscose microfiber membrane presented good reuse stability, and 17 batches of fermentation without activity loss were realized with the highest succinic acid yield of 83.20%. A microfiber membrane bioreactor was further constructed with the cell-immobilized viscose microfiber membrane to perform fermentation on a larger scale, and the concentration, yield and productivity of succinic acid were 73.20 g/L, 86.50% and 1.49 g/(L⋅h) using a fed-batch strategy, which were 124.30%, 127.60% and 124.2% of those obtained in the traditional fermenter. This study provided an approach for improving the practicality of biological succinic acid production.

Advances in functional photonic crystal materials for the analysis of chemical hazards in food.

Chemical contaminants in food generally include natural toxins (mycotoxins, animal toxins, and phytotoxins), pesticides, veterinary drugs, environmental pollutants, heavy metals, and illegal additives. Developing a low-cost, simple, and rapid detection technology for harmful substances in food is urgently needed. Analytical methods based on different advanced materials have been developed into rapid detection methods for food samples. In particular, photonic crystal (PC) materials have a unique surface periodic structure, structural color, a large surface area, easy integration with photoelectronic and magnetic devices which have great advantages in the development of rapid, low-cost, and highly sensitive analytical methods. This review focuses on the PC materials in the view of their fabrication processes, functionalized recognition components for the specific recognition of hazardous substances, and applications in the separation, enrichment, and detection of chemical hazards in real samples. Suspension array based on three-dimensional PC microspheres by droplet-based microfluidic assembly is a great promising and powerful platform for food safety detection fields. For the PCs selective analysis, biological antibodies, aptamers, and molecularly imprinted polymers (MIPs) could be modified for specific recognition of target substances, particularly MIPs because of their low-cost and easy mass production. Based on these functional PCs, various toxic and hazardous substances can be selectively enriched or recognized in real samples and further quantified in combination of liquid chromatography method or optical detection methods including fluorescence, chemiluminescence, and Raman spectroscopy.

Anatomical and functional coupling between the dorsal and ventral attention networks.

Studies have indicated that the dorsal attention network (DAN) and the ventral attention network (VAN) functionally interact via several fronto-parietal connector hubs. However, the anatomical connectivity profiles of these connector hubs, and the coupling between the anatomical and functional connectivities of them, are still unknown. In the present study, we found that functional connector hubs anatomically bridged the DAN and VAN based on multimodal magnetic resonance imaging data from the Human Connectome Project (HCP) Consortium and an independent Chinese cohort. The three hubs had unique anatomical connectivity patterns with the attention sub-networks. For each connector hub, the pattern of anatomical connectivity resembled the functional one. Finally, the strength of the anatomical connectivity of these connector hubs was positively associated with the functional connectivity at the group- and individual-levels. Our findings help to better understand the anatomical mechanisms underlying the functional interactions between the DAN and the VAN.

Prohibitin 1 (PHB1) controls growth and development and regulates proliferation and apoptosis in Schistosoma japonicum.

Schistosomiasis is a zoonotic parasitic disease caused by the trematode blood flukes of the genus Schistosoma. The prodigious egg output of females is the main cause of the disease in definitive hosts, while the female worm relies on continuous pairing with the male worm to fuel the growth and maturation of the reproductive organs and egg production. Prohibitin, which contains the functionally interdependent PHB1 and PHB2 subunits in human and some other species, has been proposed to participate in the cell proliferation and apoptosis regulation in mammals. However, little is known about the function of PHB homolog in the growth and reproductive development of schistosomes. Here, we reported the Phb1 gene that was structurally and evolutionarily conserved in Schistosoma japonicum when compared with that of other species from Caenorhabditis elegans to human. Real-time PCR detected that SjPhb1 was highly transcribed in the vitellaria of female worms. SjPhb1 knockdown achieved through the dsRNA-mediated RNAi in vivo resulted in retarded growth, decreased pairing, and fecundity in adult worms, as well as attenuated pathogenicity or virulence of worms to their hosts. Cell proliferation and apoptosis examination found decreased cell proliferation and increased cell apoptosis in SjPhb1 dsRNA-treated worms. Therefore, our study provides the first characterization of S. japonicum PHB1 and reveals its fundamental role in the regulation of growth and development of S. japonicum by specific dsRNA-mediated RNAi in vivo. Our findings prompt for a promising molecular of schistosomes that can be targeted to effectively retard the growth and development of the schistosomes.

Structural connectivity profile supports laterality of the salience network.

The salience network (SN) is mainly involved in detecting and filtering multimodal salient stimuli, and mediating the switch between the default mode network and central executive network. Early studies have indicated a right-sided dominance in the functional organization of the SN; however, the anatomical basis of the functional lateralization remains unclear. Here, we hypothesized that the structural connectivity profile between the frontoinsular cortex (FIC) and dorsal anterior cingulate cortex (dACC), which are two core hubs of the SN, is also dominant in the right hemisphere. Based on diffusion and resting-state functional magnetic resonance imaging (rfMRI) of adult healthy volunteers in independent datasets, we found a stable right-sided laterality of both the FIC-dACC structural and functional connectivity in both the human connectome project cohort and a local Chinese cohort. Furthermore, a significant effect of aging on the integrity of the right FIC-dACC structural connectivity was also identified. The right-sided laterality of the structural organization of the SN may help us to better understand the functional roles of the SN in the normal human brain.

Dysfunctional white-matter networks in medicated and unmedicated benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECT) is the most common childhood idiopathic focal epilepsy syndrome, which characterized with white-matter abnormalities in the rolandic cortex. Although diffusion tensor imaging research could characterize white-matter structural architecture, it cannot detect neural activity or white-matter functions. Recent studies demonstrated the functional organization of white-matter by using functional magnetic resonance imaging (fMRI), suggesting that it is feasible to investigate white-matter dysfunctions in BECT. Resting-state fMRI data were collected from 24 new-onset drug-naive (unmedicated [NMED]), 21 medicated (MED) BECT patients, and 27 healthy controls (HC). Several white-matter functional networks were obtained using a clustering analysis on voxel-by-voxel correlation profiles. Subsequently, conventional functional connectivity (FC) was calculated in four frequency sub-bands (Slow-5:0.01-0.027, Slow-4:0.027-0.073, Slow-3:0.073-0.198, and Slow-2:0.198-0.25 Hz). We also employed a functional covariance connectivity (FCC) to estimate the covariant relationship between two white-matter networks based on their correlations with multiple gray-matter regions. Compared with HC, the NMED showed increased FC and/or FCC in rolandic network (RN) and precentral/postcentral network, and decreased FC and/or FCC in dorsal frontal network, while these alterations were not observed in the MED group. Moreover, the changes exhibited frequency-specific properties. Specifically, only two alterations were shared in at least two frequency bands. Most of these alterations were observed in the frequency bands of Slow-3 and Slow-4. This study provided further support on the existence of white-matter functional networks which exhibited frequency-specific properties, and extended abnormalities of rolandic area from the perspective of white-matter dysfunction in BECT.

CT and MR imaging characteristics of primary hepatic lymphoma.

BACKGROUND: Primary hepatic lymphoma (PHL) is a rare primary liver tumor. The purpose of this study was to investigate the crucial imaging characteristics of PHL. METHODS: CT/MR data and clinical features of 16 patients with pathologically proven PHL were retrospectively reviewed. The assessed imaging characteristics included lesion distribution, growth appearance, density or signal characteristics, and typical signs during the dynamic enhancement. RESULTS: A total of sixteen patients were included in this study, ranging in age from 27 to 86 years (nine men and seven women; mean age, 62 years). Right upper abdominal pain, malaise, or first detection during physical examination were the chief complaint. Dynamic contrast-enhanced CT and MRI demonstrated focal masses in thirteen patients (13/16, 81%), and multiple nodules in three patients (3/16, 19%). The lesions showed vascular floating sign in 10 patients (10/16, 63%) and biliary pass-through sign in 6 patients (6/16, 37%). Necrosis in PHLs were observed in 10 patients (10/16, 63%) and presented target sign on T2WI in 5 out of 11 patients (5/11, 45%) undergoing MRI. After enhancement, PHLs had multinodular sign in the arterial phase in 10 patients (10/16, 63%), and presented washout of contrast medium in the portal-venous or delayed phase in 12 patients (12/16, 75%), pseudocapsule in the delayed phase in 15 patients (15/16, 94%), and double-ring sign in the delayed phase in 8 patients (8/16, 50%). CONCLUSION: PHL is generally seen in elderly patients with elevated beta-2-microglobulin levels. Its distinctive imaging features including obviously low ADC value, biliary/vascular floating sign, multinodular sign and double-ring sign in the delayed phase, may help to diagnose and differentiate PHL.

Intensive care of a patient undergoing combined multi-organ cluster ("larynx-trachea-thyroid-hypopharynx-esophagus") transplantation: A case report.

OBJECTIVE: The aim of this study was to summarize the intensive care experience of a patient undergoing combined multi-organ cluster ("larynx-trachea-thyroid-hypopharynx-esophagus") transplantation. METHODS: The intensive care management plan for this case was developed by a multidisciplinary team, with focus on 6 aspects: (1) stabilizing the circulation and reducing anastomotic tension by position management to improve the survival chances of transplanted organs, (2) adopting goal-directed analgesia and sedation protocols, as well as preventing anastomotic fistula, (3) implementing a bedside ultrasound-guided nutrition plan, (4) employing "body-mind" synchronous rehabilitation to facilitate functional recovery, (5) taking antirejection treatment and protective isolation measures, (6) monitoring and nursing thyroid function. RESULTS: During the intensive care, the patient's vital signs were stable. The patient was successfully weaned from the ventilator and transferred to the general ward for further treatment at 9 days postoperatively, and discharged upon recovery at 58 days postoperatively. The patient was in good condition during follow-up. CONCLUSION: This study provides reference for the care of patients who undergo similar transplantation in the future.

Preoperative prediction of renal fibrous capsule invasion in clear cell renal cell carcinoma using CT-based radiomics model.

OBJECTIVES: To develop radiomics-based classifiers for preoperative prediction of fibrous capsule invasion in renal cell carcinoma (RCC) patients by CT images. METHODS: In this study, clear cell RCC (ccRCC) patients who underwent both preoperative abdominal contrast-enhanced CT and nephrectomy surgery at our hospital were analysed. By transfer learning, we used base model obtained from Kidney Tumour Segmentation challenge dataset to semi-automatically segment kidney and tumours from corticomedullary phase (CMP) CT images. Dice similarity coefficient (DSC) was measured to evaluate the performance of segmentation models. Ten machine learning classifiers were compared in our study. Performance of the models was assessed by their accuracy, precision, recall, and area under the receiver operating characteristic curve (AUC). The reporting and methodological quality of our study was assessed by the CLEAR checklist and METRICS score. RESULTS: This retrospective study enrolled 163 ccRCC patients. The semiautomatic segmentation model using CMP CT images obtained DSCs of 0.98 in the training cohort and 0.96 in the test cohort for kidney segmentation, and DSCs of 0.94 and 0.86 for tumour segmentation in the training and test set, respectively. For preoperative prediction of renal capsule invasion, the AdaBoost had the best performance in batch 1, with accuracy, precision, recall, and F1-score equal to 0.8571, 0.8333, 0.9091, and 0.8696, respectively; and the same classifier was also the most suitable for this classification in batch 2. The AUCs of AdaBoost for batch 1 and batch 2 were 0.83 (95% CI: 0.68-0.98) and 0.74 (95% CI: 0.51-0.97), respectively. Nine common significant features for classification were found from 2 independent batch datasets, including morphological and texture features. CONCLUSIONS: The CT-based radiomics classifiers performed well for the preoperative prediction of fibrous capsule invasion in ccRCC. ADVANCES IN KNOWLEDGE: Noninvasive prediction of renal fibrous capsule invasion in RCC is rather difficult by abdominal CT images before surgery. A machine learning classifier integrated with radiomics features shows a promising potential to assist surgical treatment options for RCC patients.

Oridonin Attenuates Diabetes­induced Renal Fibrosis via the Inhibition of TXNIP/NLRP3 and NF­κB Pathways by Activating PPARγ in Rats.

INTRODUCTION: Oridonin possesses remarkable anti-inflammatory, immunoregulatory properties. However, the renoprotective effects of oridonin and the underlying molecular mechanisms in diabetic nephropathy (DN). We hypothesized that oridonin could ameliorate diabetes­induced renal fibrosis. METHODS: Streptozocin (STZ)-induced diabetic rats were provided with a high-fat diet to establish a type 2 diabetes mellitus (T2DM) animal model, and then treated with Oridonin (10, 20 mg/kg/day) for two weeks. Kidney function and renal fibrosis were assessed. High glucose-induced human renal proximal tubule epithelial cells (HK-2) were also treated with oridonin. The expression of inflammatory factors and fibrotic markers were analyzed. RESULTS: Oridonin treatment preserved kidney function and markedly limited the renal fibrosis size in diabetic rats. The renal fibrotic markers were inhibited in the oridonin 10 mg/kg/day and 20 mg/kg/day groups compared to the T2DM group. The expression of thioredoxin-interacting proteins/ nod-like receptor protein-3 (TXNIP/NLRP3) and nuclear factor (NF)­κB pathway decreased, while that of peroxisome proliferator-activated receptor-gamma (PPARγ) increased in the oridonin treatment group compared to the non-treated group. In vitro, PPARγ intervention could significantly regulate the effect of oridonin on the high glucose-induced inflammatory changes in HK-2 cells. CONCLUSION: Oridonin reduces renal fibrosis and preserves kidney function via the inhibition of TXNIP/NLRP3 and NF­κB pathways by activating PPARγ in rat T2DM model, which indicates potential effect of oridonin in the treatment of DN.

Effect of nitrogen addition on soil net nitrogen mineralization in topsoil and subsoil regulated by soil microbial properties and mineral protection: Evidence from a long-term grassland experiment.

Soil net nitrogen mineralization (Nmin), a microbial-mediated conversion of organic to inorganic N, is critical for grassland productivity and biogeochemical cycling. Enhanced atmospheric N deposition has been shown to substantially increase both plant and soil N content, leading to a major change in Nmin. However, the mechanisms underlying microbial properties, particularly microbial functional genes, which drive the response of Nmin to elevated N deposition are still being discussed. Besides, it is still uncertain whether the relative importance of plant carbon (C) input, microbial properties, and mineral protection in regulating Nmin under continuous N addition would vary with the soil depth. Here, based on a 13-year multi-level field N addition experiment conducted in a typical grassland on the Loess Plateau, we elucidated how N-induced changes in plant C input, soil physicochemical properties, mineral properties, soil microbial community, and the soil Nmin rate (Rmin)-related functional genes drove the responses of Rmin to N addition in the topsoil and subsoil. The results showed that Rmin increased significantly in both topsoil and subsoil with increasing rates of N addition. Such a response was mainly dominated by the rate of soil nitrification. Structural equation modeling (SEM) revealed that a combination of microbial properties (functional genes and diversity) and mineral properties regulated the response of Rmin to N addition at both soil depths, thus leading to changes in the soil N availability. More importantly, the regulatory impacts of microbial and mineral properties on Rmin were depth-dependent: the influences of microbial properties weakened with soil depth, whereas the effects of mineral protection enhanced with soil depth. Collectively, these results highlight the need to incorporate the effects of differential microbial and mineral properties on Rmin at different soil depths into the Earth system models to better predict soil N cycling under further scenarios of N deposition.

Genome-wide and functional analysis of late embryogenesis abundant (LEA) genes during dormancy and sprouting periods of kernel consumption apricots (P. armeniaca L. × P. sibirica L.).

Late embryogenesis abundant (LEA) proteins play a crucial role in protecting cells from stress, making them potential contributors to abiotic stress tolerance. This study focuses on apricot (P. armeniaca L. × P. sibirica L.), where a comprehensive genome-wide analysis identified 54 LEA genes, categorized into eight subgroups based on phylogenetic relationships. Synteny analysis revealed 14 collinear blocks containing LEA genes between P. armeniaca × P. sibirica and Arabidopsis thaliana, with an additional 9 collinear blocks identified between P. armeniaca × P. sibirica and poplar. Examination of gene structure and conserved motifs indicated that these subgroups exhibit consistent exon-intron patterns and shared motifs. The expansion and duplication of LEA genes in P. armeniaca × P. sibirica were driven by whole-genome duplication (WGD), segmental duplication, and tandem duplication events. Expression analysis, utilizing RNA-seq data and quantitative real-time RT-PCR (qRT-PCR), indicated induction of PasLEA2-20, PasLEA3-2, PasLEA6-1, Pasdehydrin-3, and Pasdehydrin-5 in flower buds during dormancy and sprouting phases. Coexpression network analysis linked LEA genes with 15 cold-resistance genes. Remarkably, during the four developmental stages of flower buds in P. armeniaca × P. sibirica - physiological dormancy, ecological dormancy, sprouting period, and germination stage - the expression patterns of all PasLEAs coexpressed with cold stress-related genes remained consistent. Protein-protein interaction networks, established using Arabidopsis orthologs, emphasized connections between PasLEA proteins and cold resistance pathways. Overexpression of certain LEA genes in yeast and Arabidopsis conferred advantages under cold stress, including increased pod length, reduced bolting time and flowering time, improved survival and seed setting rates, elevated proline accumulation, and enhanced antioxidative enzymatic activities. Furthermore, these overexpressed plants exhibited upregulation of genes related to flower development and cold resistance. The Y1H assay confirmed that PasGBF4 and PasDOF3.5 act as upstream regulatory factors by binding to the promoter region of PasLEA3-2. PasDOF2.4, PasDnaJ2, and PasAP2 were also found to bind to the promoter of Pasdehydrin-3, regulating the expression levels of downstream genes. This comprehensive study explores the evolutionary relationships among PasLEA genes, protein interactions, and functional analyses during various stages of dormancy and sprouting in P. armeniaca × P. sibirica. It offers potential targets for enhancing cold resistance and manipulating flower bud dormancy in this apricot hybrid.

Chronic kidney disease and NLRP3 inflammasome: Pathogenesis, development and targeted therapeutic strategies.

Chronic kidney disease (CKD) is a global health concern and public health priority. The condition often involves inflammation due to the accumulation of toxins and the reduced clearance of inflammatory cytokines, leading to gradual loss of kidney function. Because of the tremendous burden of CKD, finding effective treatment strategies against inflammation is crucial. Substantial evidence suggests an association between kidney disease and the inflammasome. As a well-known multiprotein signaling complex, the NLR family pyrin domain containing 3 (NLRP3) inflammasome plays an important role in inducing renal inflammation and fibrosis. Small molecule inhibitors targeting the NLRP3 inflammasome are potential agents for the treatment of CKD.The NLRP3 inflammasome activation amplifies the inflammation response, promoting pyroptotic cell death. Thus, it may contribute to the onset and progression of CKD, but the mechanism behind inflammasome activation in CKD remains obscure.In this review, we summarized recent findings on the role of the NLRP3 inflammasome in CKD and new strategies targeting the NLRP3 inflammasome.

Hemoglobin to red cell distribution width ratio as a prognostic marker for ischemic stroke after mechanical thrombectomy.

Background: The hemoglobin to red cell distribution width ratio (HRR) has been experimentally associated with the prognosis of acute ischemic stroke (AIS). However, its relationship with mechanical thrombectomy (MT) for AIS remains unclear. Therefore, this study aimed to investigate the relationship between HRR at admission, follow-up HRR, and clinical outcomes in patients undergoing MT. Methods: Acute ischemic stroke patients undergoing MT were consecutively enrolled from January 2017 to December 2022. Demographic, clinical, and laboratory information were collected. HRR was measured by dividing hemoglobin (Hb) by red cell distribution width (RDW) at admission and after 24 h of MT. Clinical outcomes after 3 months were evaluated using the modified Rankin Scale (mRS). The primary outcome was poor prognosis (mRS > 2) at 3 months, while the secondary outcome was death within 3 months. Results: A total of 310 patients were analyzed, of whom 216 patients (69.7%) had poor prognosis, and 92 patients (29.6%) died. Patients with a poor prognosis and death had significantly lower HRR levels at admission and after 24 h. HRR at admission was not associated with clinical outcomes according to multivariable logistic regression analysis. However, HRR after 24 h was significantly associated with poor prognosis (adjusted odds ratio [OR]: 0.646, 95% confidence interval [CI]: 0.520-0.803, p < 0.001) and death (adjusted OR: 0.615, 95% CI: 0.508-0.744, p < 0.001). Receiver-operating characteristic curve analysis demonstrated the predictive ability of HRR after 24 h, with areas under the curves of 0.790 for poor prognosis and 0.771 for death. Conclusion: Rapidly measurable HRR levels are an independent marker of outcome after MT in AIS patients. This may provide a reliable auxiliary outcome measure for clinical routine and interventional therapy.

Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome.

Intermittent hypoxia is the best predictor of developing cognitive decline and Alzheimer's disease progression in patients with obstructive sleep apnea. The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome has been poorly studied as a regulator of neuroinflammation in cognitive impairment caused by intermittent hypoxia. As critical inflammatory cells, exosomes secreted by microglia have been found to affect the spread of pathologic proteins and neuropathology in neurodegenerative diseases. However, the effects of microglial exosomes on neuroinflammation and cognitive outcomes after intermittent hypoxia remain unclear. In this study, the role of miRNAs in microglial exosomes in improving cognitive deficits in mice exposed to intermittent hypoxia was investigated. We demonstrated that miR-146a-5p fluctuated over time in microglial exosomes of mice exposed to intermittent hypoxia for different periods of time, which could regulate neuronal NLRP3 inflammasome and neuroinflammation. In primary neurons, we found that miR-146a-5p regulated mitochondrial reactive oxygen species by targeting HIF1α, thus affecting the NLRP3 inflammasome and secretion of inflammatory factors. Similarly, further studies showed that inhibition of NLRP3 by administering overexpressed miR-146a-5p in microglial exosomes and MCC950 has improved neuroinflammation and cognitive dysfunction in mice after intermittent hypoxia. In conclusion, NLRP3 inflammasome may be a regulatory target for ameliorating cognitive impairment caused by intermittent hypoxia, and microglial exosomal miR-146a-5p may be a promising therapeutic strategy.

Combined effect of cortical superficial siderosis and cerebral microbleed on short-term and long-term outcomes after intracerebral haemorrhage.

BACKGROUND AND PURPOSE: Cortical superficial siderosis (cSS) and cerebral microbleed (CMB) have distinct effects on intracerebral haemorrhage (ICH). We aim to investigate the combined effect of cSS and CMB on outcomes after ICH. METHODS: Based on a single-centre stroke registry database, patients with spontaneous ICH who had CT scan within 48 hours after ictus and MRI subsequently were identified. Eligible patients were divided into four groups (cSS-CMB-, cSS-CMB+, cSS+CMB-, cSS+CMB+) according to cSS and CMB on susceptibility-weighted image of MRI. Primary outcomes were haematoma volume on admission and unfavourable outcome defined as modified Rankin Scale scores ≥3 at 3 months. Secondary outcomes were all-cause death, recurrence of stroke and ICH during follow-up (median follow-up 2.0 years, IQR 1.0-3.0 years). RESULTS: A total of 673 patients were identified from 1044 patients with spontaneous ICH. 131 (19.5%) had cSS and 468 (69.5%) had CMB. Patients with cSS+CMB+ had the highest rate of poor outcome at 3 months, as well as all-cause death, recurrent stroke and ICH during follow-up. In cSS- patients, CMB was associated with smaller haematoma (ß -0.13; 95% CI -0.22 to -0.03; p=0.009), but it still increased risks of recurrent ICH (OR 4.6; 95% CI 1.3 to 15.6; p=0.015) and stroke (OR 2.0; 95% CI 1.0 to 4.0; p=0.049). These effects of CMB became unremarkable in the context of cSS+. CONCLUSIONS: Patients with different combinations of cSS and CMB have distinct patterns of short-term and long-term outcomes. Although CMB is related to restrained haematoma, it does not improve long-term outcomes. TRIAL REGISTRATION NUMBER: NCT04803292.