Non-canonical pattern recognition of a pathogen-derived metabolite by a nuclear hormone receptor identifies virulent bacteria in C. elegans.

Distinguishing infectious pathogens from harmless microorganisms is essential for animal health. The mechanisms used to identify infectious microbes are not fully understood, particularly in metazoan hosts that eat bacteria as their food source. Here, we characterized a non-canonical pattern-recognition system in Caenorhabditis elegans (C. elegans) that assesses the relative threat of virulent Pseudomonas aeruginosa (P. aeruginosa) to activate innate immunity. We discovered that the innate immune response in C. elegans was triggered by phenazine-1-carboxamide (PCN), a toxic metabolite produced by pathogenic strains of P. aeruginosa. We identified the nuclear hormone receptor NHR-86/HNF4 as the PCN sensor in C. elegans and validated that PCN bound to the ligand-binding domain of NHR-86/HNF4. Activation of NHR-86/HNF4 by PCN directly engaged a transcriptional program in intestinal epithelial cells that protected against P. aeruginosa. Thus, a bacterial metabolite is a pattern of pathogenesis surveilled by nematodes to identify a pathogen in its bacterial diet.

Boron supply restores aluminum-blocked auxin transport by the modulation of PIN2 trafficking in the root apical transition zone.

The supply of boron (B) alleviates the toxic effects of aluminum (Al) on root growth; however, the mechanistic basis of this process remains elusive. This study filled this knowledge gap, demonstrating that boron modifies auxin distribution and transport in Al-exposed Arabidopsis roots. In B-deprived roots, treatment with Al induced an increase in auxin content in the root apical meristem zone (MZ) and transition zone (TZ), whereas in the elongation zone (EZ) the auxin content was decreased beyond the level required for adequate growth. These distribution patterns are explained by the fact that basipetal auxin transport from the TZ to the EZ was disrupted by Al-inhibited PIN-FORMED 2 (PIN2) endocytosis. Experiments involving the modulation of protein biosynthesis by cycloheximide (CHX) and transcriptional regulation by cordycepin (COR) demonstrated that the Al-induced increase of PIN2 membrane proteins was dependent upon the inhibition of PIN2 endocytosis, rather than on the transcriptional regulation of the PIN2 gene. Experiments reporting on the profiling of Al3+ and PIN2 proteins revealed that the inhibition of endocytosis of PIN2 proteins was the result of Al-induced limitation of the fluidity of the plasma membrane. The supply of B mediated the turnover of PIN2 endosomes conjugated with indole-3-acetic acid (IAA), and thus restored the Al-induced inhibition of IAA transport through the TZ to the EZ. Overall, the reported results demonstrate that boron supply mediates PIN2 endosome-based auxin transport to alleviate Al toxicity in plant roots.

PIN2/3/4 auxin carriers mediate root growth inhibition under conditions of boron deprivation in Arabidopsis.

The mechanistic basis by which boron (B) deprivation inhibits root growth via the mediation of root apical auxin transport and distribution remains elusive. This study showed that B deprivation repressed root growth of wild-type Arabidopsis seedlings, which was related to higher auxin accumulation (observed with DII-VENUS and DR5-GFP lines) in B-deprived roots. Boron deprivation elevated the auxin content in the root apex, coinciding with upregulation of the expression levels of auxin biosynthesis-related genes (TAA1, YUC3, YUC9, and NIT1) in shoots, but not in root apices. Phenotyping experiments using auxin transport-related mutants revealed that the PIN2/3/4 carriers are involved in root growth inhibition caused by B deprivation. B deprivation not only upregulated the transcriptional levels of PIN2/3/4, but also restrained the endocytosis of PIN2/3/4 carriers (observed with PIN-Dendra2 lines), resulting in elevated protein levels of PIN2/3/4 in the plasma membrane. Overall, these results suggest that B deprivation not only enhances auxin biosynthesis in shoots by elevating the expression levels of auxin biosynthesis-related genes but also promotes the polar auxin transport from shoots to roots by upregulating the gene expression levels of PIN2/3/4, as well as restraining the endocytosis of PIN2/3/4 carriers, ultimately resulting in auxin accumulation in root apices and root growth inhibition.

Small extracellular vesicles-transported lncRNA TDRKH-AS1 derived from AOPPs-treated trophoblasts initiates endothelial cells pyroptosis through PDIA4/DDIT4 axis in preeclampsia.

BACKGROUND: Substantial studies have demonstrated that oxidative stress placenta and endothelial injury are considered to inextricably critical events in the pathogenesis of preeclampsia (PE). Systemic inflammatory response and endothelial dysfunction are induced by the circulating factors released from oxidative stress placentae. As a novel biomarker of oxidative stress, advanced oxidation protein products (AOPPs) levels are strongly correlated with PE characteristics. Nevertheless, the molecular mechanism underlying the effect of factors is still largely unknown. METHODS: With the exponential knowledge on the importance of placenta-derived extracellular vesicles (pEVs), we carried out lncRNA transcriptome profiling on small EVs (sEVs) secreted from AOPPs-treated trophoblast cells and identified upregulated lncRNA TDRKH-AS1 as a potentially causative factor for PE. We isolated and characterized sEVs from plasma and trophoblast cells by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting. The expression and correlation of lncRNA TDRKH-AS1 were evaluated using qRT-PCR in plasmatic sEVs and placentae from patients. Pregnant mice injected with TDRKH-AS1-riched trophoblast sEVs was performed to detect the TDRKH-AS1 function in vivo. To investigate the potential effect of sEVs-derived TDRKH-AS1 on endothelial function in vitro, transcriptome sequencing, scanning electron Microscopy (SEM), immunofluorescence, ELISA and western blotting were conducted in HUVECs. RNA pulldown, mass spectrometry, RNA immunoprecipitation (RIP), chromatin isolation by RNA purification (ChIRP) and coimmunoprecipitation (Co-IP) were used to reveal the latent mechanism of TDRKH-AS1 on endothelial injury. RESULTS: The expression level of TDRKH-AS1 was significantly increased in plasmatic sEVs and placentae from patients, and elevated TDRKH-AS1 in plasmatic sEVs was positively correlated with clinical severity of the patients. Moreover, pregnant mice injected with TDRKH-AS1-riched trophoblast sEVs exhibited a hallmark feature of PE with increased blood pressure and systemic inflammatory responses. Pyroptosis, an inflammatory form of programmed cell death, is involved in the development of PE. Indeed, our in vitro study indicated that sEVs-derived TDRKH-AS1 secreted from AOPPs-induced trophoblast elevated DDIT4 expression levels to trigger inflammatory response of pyroptosis in endothelial cells through interacting with PDIA4. CONCLUSIONS: Herein, results in the present study supported that TDRKH-AS1 in sEVs isolated from oxidative stress trophoblast may be implicated in the pathogenesis of PE via inducing pyroptosis and aggravating endothelial dysfunction.

[Application of Midline Catheter Placed Under Ultrasound Guidance in Intravenous Therapy for Oral and Maxillofacial Tumor].

Objective: To examine the application effect of ultrasound-guided placement of midline catheter and to select the appropriate placement method of intravenous catheter for patients with oral and maxillofacial tumors. Methods: We retrospectively analyzed the general data and venous catheter-related information of 143 oral and maxillofacial tumor patients who received treatment between June 2019 and December 2021. There were two patient groups, a control group of patients with inserted peripheral venous catheters (PVC) and an observation group of patients with midline catheters placed under ultrasound guidance. We made a comparative analysis of the incidence of catheter-related complications, including bleeding at the insertion site, phlebitis, catheter blockage, extravasation, etc., in the two groups. When the baseline data from the two groups were not balanced, we used propensity score matching (PSM) to match the general data before comparing the complication incidence between the two groups. Results: There were 71 patients who underwent 215 times of PVC placement in the control group and 72 patients who underwent 72 times of midline catheter placement in the observation group. There was no significant difference between the patients in the two groups in terms of age, sex, diagnosis, or the use of anticoagulant medication ( P>0.05) . The observation group had longer average length-of-stay than the control group did ( P<0.01). The cost of catheter placement in the observation group was 1080 yuan per set, with the average daily cost being about (56.27±20.23) yuan. Patients in the control group had PVC placement for an average of (3.03±0.93) times. The cost for PVC placement was 96 yuan per time and the average daily cost was about (19.94±7.50) yuan. There was significant difference in the average daily cost between the observation group and the control group ( P<0.01). PSM was performed for the two groups. Before PSM, the incidence of catheter-related complications in the observation group (8.3%, 6/72) was lower than that of the control group (30.2%, 65/215) and the difference was statistically significant ( P<0.01). After PSM, 72 times of catheter placement from each group were included in comparative analysis. The incidence of catheter-related complications in the observation group (8.3%, 6/72) was lower than that of the control group (54.2%, 39/72) and the difference was statistically significant ( P<0.01). Conclusion: Patients have low incidence of catheter-related complications when they have midline catheter placed under ultrasound guidance, which helps reduce the pain of repeated venous insertion that patients incur and the workload of clinical nurses. The use of midline catheters is appropriate for and should be popularized among patients with oral and maxillofacial malignant tumors, especially patients who have poor peripheral venous conditions and those who are undergoing repair and reconstruction surgeries.

Nutritional status in patients of mandibular osteoradionecrosis: A single-institution experience.

BACKGROUND: Mandibular osteoradionecrosis (ORN) is a devastating complication secondary to the radiotherapy of head and neck cancer. The nutritional status of ORN patients is compromised, but remains rarely studied. We aimed to evaluate the overall nutritional status of patients with ORN and explore the risk factors behind poor nutrition. METHODS: This is a single-institution cross-sectional study. Patients diagnosed with ORN were consecutively recruited in a tertiary teaching hospital from July 2017 to August 2019. Multiple laboratory markers and physical indicators were examined to profile their nutritional status. The potential risk factors of poor nutrition were explored by logistic regression. RESULTS: A total of 107 patients with ORN were recruited. Among them, almost all patients (95.3%) had at least one laboratory marker lower than the normal physiological range. A total of 40 (37.5%) patients were categorized as undernutrition, who had lower serum albumin (mean difference: 1.8 ± 0.8 g/L; p = .02), prealbumin (mean difference: 26.8 ± 10.8 mg/L; p = .02), and BMI (3.8 ± 0.4 kg/m2 ; p < .0001) compared to patients of normal nutrition. Notably, the multivariate logistic regression indicated that patients with semi-liquid diet had 14.41 (95% CI: 3.03-68.54, p = .001) times; patients with liquid diet had 5.70 (95% CI: 1.55-20.98, p = .009) times more likely to be in undernutrition, as compared to patients with regular diets. CONCLUSIONS: This is the first study characterizing the poor nutritional status in ORN patients. Patients having semi-liquid or liquid diets tended to have poorer nutritional status. The nutritional status of ORN patients should be underlined for professional nutritional supports so as to enhance their quality of life. More studies are warranted.

Risk factors and nomogram for predicting carotid blowout syndrome based on computed tomography angiography.

OBJECTIVES: To identify independent factors for head and neck cancer (HNC) patients with carotid blowout syndrome (CBS) and construct a nomogram to predict risk of CBS preoperatively based on computed tomography angiography (CTA) imaging. SUBJECT AND METHODS: From January 2010 to July 2020, 73 HNC patients who had surgery in hospitalization and underwent CTA examination for head and neck region were included in this study. Vascular alterations and the relationship between carotid artery (CA) and tumor were evaluated in CTA. Clinical and CTA imaging features were distinguished by logistic regression analysis and used to perform receiver operating curve analysis. Nomogram was created to predict risk of CBS and assessed by concordance index (C-index) and calibration curve. RESULTS: Three independent risk factors were identified, including radical neck dissection, CA surrounded by tumor, and CA invaded by tumor without clear boundary. Area under curve of the combination of 3 variables was 0.836 (95% CI, 0.72-0.952, p < 0.001). The C-index of nomogram was 0.84 (95% CI, 0.73-0.94), and the calibration plot showed a good fitting between prediction and observation. CONCLUSIONS: We established a useful nomogram based on CTA imaging, which showed a satisfied efficacy for evaluating risk of CBS in HNC patients preoperatively.

Associations between meteorological variation and rupture of intracranial aneurysm in Fujian, China: A 5-year multicenter study.

OBJECTIVE: By exploring the exposure-response relationships between meteorological factors and rupture of intracranial aneurysm (IA) to reveal the influence of meteorological variation on IA rupture under the specific climate in Fujian, China. METHOD: 7515 cases of IA rupture from several municipal medical institutions in Fujian Province as well as local meteorological data during the same period were collected from 2013 to 2017. Poisson regression and Spearman correlation analysis were applied to explore the distribution characteristics of IA rupture and how it is associated with meteorological parameters. Poisson generalized additive model was established to further analyze the exposure-response relationships between meteorological factors and IA rupture, and its hysteresis effects. RESULT: The IA rupture exhibited a negative correlation with temperature (rs = -0.323, 95% CI: -0.539 ~ -0.068) and a positive correlation with atmospheric pressure (rs = 0.397, 95% CI: 0.152-0.597) or pressure difference (rs = 0.296, 95% CI: 0.038-0.517), 21.05 â„ƒ and 1000.14 hPa were the risk thresholds for the onset ascribed to variation in temperature and atmospheric pressure, respectively. Temperature and atmospheric pressure also exerted hysteresis effects on IA rupture. Cold will increase the rupture risk in the subsequent 1-3 days, and high pressure will raise the morbidity in the next 1-2 days. Besides, drastic variations in temperature and atmospheric pressure were also associated with the higher risk of IA rupture in the next 2 days and 1 day, respectively. CONCLUSION: Temperature and atmospheric pressure have a negative and positive correlation with IA rupture in Fujian, China, respectively. Variation in temperature and atmospheric pressure exert different degrees of hysteresis effects on IA rupture.

High-Throughput Data Reveals Novel Circular RNAs via Competitive Endogenous RNA Networks Associated with Human Intracranial Aneurysms.

BACKGROUND Little is known about epigenetic regulation of intracranial aneurysms (IAs). Circular non-coding RNAs (circRNAs) play crucial roles in cardiovascular diseases, but they have received scant research attention regarding their relationship with IAs. This study aimed to explore new pathological mechanisms of IA through circRNA expression profiles and to provide novel therapeutic strategies. MATERIAL AND METHODS The comprehensive circRNA and mRNA expression profiles were detected by RNA-Seq in human IA walls and superficial temporal arteries (STAs). The RNA-Seq findings were validated by qRT-PCR. GO and KEGG analyses indicated the functions of these circRNAs. A competing endogenous RNA (ceRNA) network was constructed to reveal the circRNA-miRNA-mRNA relationship. Two newly discovered circRNAs were further detected in peripheral blood of IA patients and healthy people to clarify their expression patterns in the periphery. RESULTS Many differentially expressed circRNAs are closely involved in immune/inflammatory response and cell adhesion/adherens junction. The novel circRNAs (hsa_circ_0072309 and hsa_circ_0008433) regulate DDR2 and MMP2, respectively, which are associated with SMC dysfunction and vascular injury through ceRNA. Moreover, we found differential expression of these 2 circRNAs in the peripheral blood of IA patients, and the expression pattern of hsa_circ_0072309 had central and peripheral consistency. CONCLUSIONS To the best of our knowledge, this is the first study to perform circRNA sequencing analysis of IAs. hsa_circ_0072309 and hsa_circ_0008433 are novel and pivotal circRNAs related to IAs. This study provides new insights into therapeutic targets and biomarkers for IA patients.

Association Between the 4p16 Susceptibility Locus and the Risk of Atrial Septal Defect in Population from Southeast China.

Three single nucleotide polymorphisms (SNPs), rs16835979, rs870142 and rs6824295, located in chromosome 4p16 were associated with the risk of ostium secundum atrial septal defect (ASD) in the European population. The 4p16 susceptibility locus in congenital heart disease was replicated in Chinese populations. Here, we analyzed the associations between these three SNPs and ASD in Chinese population from Fujian Province in southeast China. We conducted a case-control study by genotyping three SNPs in 354 non-syndromic ASD patients and 557 non-CHD control subjects. Logistic regression analyses showed that the genotype and allele frequencies of these three SNPs were significantly different between the cases and controls in Fujian Chinese population. The allele A of rs870142, the allele A of rs16835979 and the allele A of rs6824295 were significantly associated with an increased risk of ASD. According to the analysis of the three SNPs, the haplotype of AAA was associated with a significantly increased risk of ASD. Our study further supports that these three SNPs confer the predisposition to ASD phenotype in Chinese population.

No association of pri-miR-143 rs41291957 polymorphism with the risk of congenital heart disease in a Chinese population.

MiR-143 plays an important role in the heart development of zebra fish. The rs41291957 variant located in the pri-miR-143 sequence is associated with colorectal carcinogenesis. Therefore, the authors hypothesized that rs41291957 in pri-miR-143 might be involved in the risk of sporadic congenital heart disease (CHD). The authors conducted a case-control study of CHD in a Chinese population to test their hypothesis by genotyping pri-miR-143 rs41291957 in 1,109 CHD cases and 915 non-CHD control subjects. Logistic regression analyses showed no significant association of genotype or allele frequencies of pri-miR-143 rs41291957 A/G polymorphism with the CHD cases in overall or various subtypes compared with the control group. To the authors' knowledge, this is the first study to investigate the relationship between miR-143 and CHD cases. The results demonstrated that rs41291957 in pri-miR-143 has no major role in genetic susceptibility to sporadic CHD, at least in the current study population.

OTAMatch: Optimal Transport Assignment with PseudoNCE for Semi-supervised Learning.

In semi-supervised learning (SSL), many approaches follow the effective self-training paradigm with consistency regularization, utilizing threshold heuristics to alleviate label noise. However, such threshold heuristics lead to the underutilization of crucial discriminative information from the excluded data. In this paper, we present OTAMatch, a novel SSL framework that reformulates pseudo-labeling as an optimal transport (OT) assignment problem and simultaneously exploits data with high confidence to mitigate the confirmation bias. Firstly, OTAMatch models the pseudo-label allocation task as a convex minimization problem, facilitating end-to-end optimization with all pseudo-labels and employing the Sinkhorn-Knopp algorithm for efficient approximation. Meanwhile, we incorporate epsilon-greedy posterior regularization and curriculum bias correction strategies to constrain the distribution of OT assignments, improving the robustness with noisy pseudo-labels. Secondly, we propose PseudoNCE, which explicitly exploits pseudo-label consistency with threshold heuristics to maximize mutual information within self-training, significantly boosting the balance of convergence speed and performance. Consequently, our proposed approach achieves competitive performance on various SSL benchmarks. Specifically, OTAMatch substantially outperforms the previous state-of-the-art SSL algorithms in realistic and challenging scenarios, exemplified by a notable 9.45% error rate reduction over SoftMatch on ImageNet with 100K-label split, underlining its robustness and effectiveness.

Effects of exercise combined with cervicothoracic spine self-mobilization on chronic non-specific neck pain.

To investigate the short-term effects and differences between exercise alone and exercise combined with self-mobilization training on chronic non-specific neck pain (CNSNP). Thirty subjects who met the criteria were recruited and randomly assigned to the exercise training group, the exercise combined with cervical self-mobilization training group (ECCM), and the exercise combined with cervicothoracic self-mobilization training group (ECCTM). The exercise training group received 6 weeks of deep neck flexor under biofeedback and scapular stability training, and the other two groups received 6 weeks of cervical self-mobilization and cervicothoracic self-mobilization, respectively, in addition to exercise training. Neck pain, cervical range of motion (ROM), neck disability, strength and endurance of deep neck flexor and quality of life were assessed before and after 6 weeks of training. The study results showed that all the three training programs for 6 weeks increased the strength and endurance of deep neck flexor, increased cervical ROM, reduced pain, and improved neck function (P < 0.05). The exercise combined with self-mobilization two groups compared with only the exercise training group had better improvement in ROM of extension, lateral flexion, rotation and quality of life (P < 0.05). Compared with exercise alone and exercise combined with cervical self-mobilization training, the exercise combined with cervicothoracic self-mobilization training was the best in improving ROM of right lateral flexion (exercise training group vs ECCTM: P < 0.01, d = 1.61, ECCM vs ECCTM: P < 0.05, d = 1.14) and pain (exercise training group vs ECCTM: P < 0.05, d = 1.34, ECCM vs ECCTM: P < 0.05, d = 1.23). Deep flexor muscle and shoulder stability training can improve the endurance and strength of the deep flexor muscles of the neck and coordinate the movement patterns of the shoulder and neck. Self-mobilization techniques can promote improvements in cervical lateral flexion and rotation range of motion, alleviate neck disability and further improve quality of life. A combination of exercise and cervicothoracic self-mobilization training appears beneficial for the management of neck pain.

Cortical Changes of Dual Cognitive-Task Balance Training in Patients with Chronic Ankle Instability: A Randomized Trial.

CONTEXT: Researchers have shown that patients with chronic ankle instability (CAI) have deficits in memory and attention allocation. This functional deficit affects the lower extremity performance. Motor-cognitive dual-task training may improve lower limb dysfunction caused by central nervous system injury. Whether dual-task training is more favorable than single-task training for neuromuscular control in patients with single-task training still needs to be further proven. OBJECTIVE: To determine whether balance-cognitive dual-task training can influence cortical activity and has more effective treatment effects than balance single-task training. DESIGN: Randomized controlled clinical trial (Clinical Trials: XXX). SETTING: Rehabilitation training room. PATIENTS OR OTHER PARTICIPANTS: After recruitment, twenty-four patients with CAI (age=22.33±2.43 years, height=175.62±7.7 cm, mass=70.63±14.59 kg) were block randomized into two groups. INTERVENTION(S): Protocols were performed three times per week for six weeks. The single-task group underwent one-leg static balance training with and without vision and hopping balance training. The dual-task group underwent balance and cognitive training (backward counting task). MAIN OUTCOME MEASURE(S): The follow variables were assessed before and after the interventions: cortical activity, proprioception, muscle onset time, and dynamic balance. We performed MANOVAs to compare changes of main effects and interactions across groups and time. A post-hoc Bonferroni test was performed for pairwise comparisons when there were significant interactions with the MANOVAs. RESULTS: Twenty-four participants successfully completed the six-week interventions. Proprioception, peroneus longus muscle onset time, and dynamic postural control improved significantly after the interventions in both groups (P<0.05). Dual-task training was superior to single-task training in improving JPS plantarflexion, shortening peroneus longus muscle onset time, and altering cortical activity(P<0.05). CONCLUSIONS: A six-week balance training program or balance combined with cognitive training could improve the functional deficits associated with CAI. Meanwhile, the dual-task training could improve cortical activity and lower extremity function.

VqNAC44 enhances stilbene synthesis and disease resistance in Chinese wild grape by interacting with VqMYB15.

As significant phytoalexins, stilbene compounds can improve the stress resistance of grapes under biotic and abiotic stress conditions and have biological effects such as antitumour, antioxidant, immune regulation and cardiovascular protection activities in humans. RESVERATROL SYNTHASE (RS), also known as STILBENE SYNTHASE (STS), is the critical enzyme regulating stilbene synthesis and has been identified in a few plant species. However, the regulatory mechanisms of stilbene synthesis are uncertain. In this study, an NAC family transcription factor from Vitis quinquangularis, named VqNAC44, was characterized as an indirect regulator of stilbene synthesis. It is worth noting that VqNAC44 did not bind to the STS promoter nor did it interact with the STS protein but interacted with the MYB transcription factor VqMYB15. This interaction between VqMYB15 and VqNAC44 was validated by a yeast two-hybrid assay and bimolecular fluorescence complementation. Overexpressing VqNAC44 in Arabidopsis thaliana significantly increased its tolerance to biotic and abiotic stresses. Transient overexpression of VqNAC44 and VqMYB15 in grape leaves resulted in increased expression of the STS gene and increased production of stilbene compounds. The experimental results confirmed that VqNAC44 regulated stilbene synthesis by interacting with VqMYB15, thereby enhancing the plant stress resistance.

Detection of common pathogenesis of rheumatoid arthritis and atherosclerosis via microarray data analysis.

Despite extensive research reveal rheumatoid arthritis (RA) is related to atherosclerosis (AS), common pathogenesis between these two diseases still needs to be explored. In current study, we explored the common pathogenesis between rheumatoid arthritis (RA) and atherosclerosis (AS) by identifying 297 Differentially Expressed Genes (DEGs) associated with both diseases. Through KEGG and GO functional analysis, we highlighted the correlation of these DEGs with crucial biological processes such as the vesicle transport, immune system process, signaling receptor binding, chemokine signaling and many others. Employing Protein-Protein Interaction (PPI) network analysis, we elucidated the associations between DEGs, revealing three gene modules enriched in immune system process, vesicle, signaling receptor binding, Pertussis, and among others. Additionally, through CytoHubba analysis, we pinpointed 11 hub genes integral to intergrin-mediated signaling pathway, plasma membrane, phosphotyrosine binding, chemokine signaling pathway and so on. Further investigation via the TRRUST database identified two key Transcription Factors (TFs), SPI1 and RELA, closely linked with these hub genes, shedding light on their regulatory roles. Finally, leveraging the collective insights from hub genes and TFs, we proposed 10 potential drug candidates targeting the molecular mechanisms underlying RA and AS pathogenesis. Further investigation on xCell revealed that 14 types of cells were all different in both AS and RA. This study underscores the shared pathogenic mechanisms, pivotal genes, and potential therapeutic interventions bridging RA and AS, offering valuable insights for future research and clinical management strategies.

FeNi-MIL-88B-based electrochemiluminescence immunosensor for ultra-sensitive detection of CD44 protein via dual-quenching strategy.

BACKGROUND: Cluster of Differentiation 44 (CD44) is considered an important biomarker for various cancers, and achieving highly sensitive detection of CD44 is crucial, which plays a significant role in tumor invasion and metastasis, providing essential information for clinical tumor diagnosis. Commonly used methods for analysis include fluorescence spectroscopy (FL), photoelectrochemical analysis (PEC), electrochemical analysis (EC), and commercial ELISA kits. Although these methods offer high sensitivity, they can be relatively complex to perform experimentally. Electrochemiluminescence (ECL) has gained widespread research attention due to its high sensitivity, ease of operation, effective spatiotemporal control, and close to zero background signal. RESULTS: In this work, a sandwich-type ECL immunosensor for detecting CD44 was constructed using luminol as a luminophore. In this sensing platform, bimetallic MOFs (Pd@FeNi-MIL-88B) loaded with palladium nanoparticles (Pd NPs) were used as a novel enzyme mimic, exhibiting excellent catalytic performance towards the electroreduction of H2O2. The hybrids provided a strong support platform for luminol and antibodies, significantly enhancing the initial ECL signal of luminol. Subsequently, core-shell Au@MnO2 nanocomposites were synthesised by gold nanoparticles (Au NPs) encapsulated in manganese dioxide (MnO2) thin layers, as labels. In the luminol/H2O2 system, Au@MnO2 exhibited strong light absorption in the broad UV-vis spectrum, similar to the black body effect, and the scavenging effect of Mn2+ on O2•-, which achieved the dual-quenching of ECL signal. Under the optimal experimental conditions, the immunosensor demonstrated a detection range of 0.1 pg mL-1 - 100 ng mL-1, with a detection limit of 0.069 pg mL-1. SIGNIFICANCE: Based on Pd@FeNi-MIL-88B nanoenzymes and Au@MnO2 nanocomposites, a dual-quenching sandwich-type ECL immunosensor for the detection of CD44 was constructed. The proposed immunosensor exhibited excellent reproducibility, stability, selectivity, and sensitivity, and provided a valuable analytical strategy and technical platform for the accurate detection of disease biomarkers, and opened up potential application prospects for early clinical treatment.

Synergetic-effect-enhanced electrochemiluminescence of zein-protected Au-Ag bimetallic nanoclusters for CA15-3 detection.

In this work, a sandwich-type electrochemiluminescence (ECL) system was constructed for the detection of CA15-3. Gold-silver bimetallic nanoclusters (Au-Ag BNCs) with zein as a protective ligand were synthesized, and the excellent ECL performance of this material was demonstrated for the first time. Zein carrying a variety of groups that ligated with Au-Ag BNCs, forming a protective shell of zein, effectively prevented clusters from aggregating or growing into larger nanoparticles. The synergistic effect of the bimetal promotes the ECL emission, making this nanoscale material an ideal ECL probe. GO-PANI, which effectively promoting the production of sulfate radicals of the co-reactant and significantly increasing the ECL strength, was a good sensing platform for antibody immobilization. Consequently, we constructed an ECL sensor with GO-PANI as the sensing platform and Au-Ag BNCs@zein as the ECL probe, with a detection range of 0.001-100 U mL-1 and a detection limit of 0.0003 U mL-1, provided a strong support for the sensor for future CA15-3 detection applications.

Quantification of placental extracellular vesicles in different pregnancy status via single particle analysis method.

BACKGROUND: The nano-sized, lipid bilayer-delimited placental extracellular vesicles (PEVs) released by the placenta are now regarded as important mediators involved in various physiological and pathological processes of pregnant women. The number and contents of PEVs are significantly altered in preeclampsia and are considered as potential biomarkers. However, the distribution pattern of PEVs in the maternal circulation in different pregnancy status is still unclear for the limitation of the traditional method with low sensitivity. METHODS: In this work, we recruited 561 pregnant women with different pregnancy status and investigated the distribution pattern of PEVs in the maternal circulation based on a single extracellular vesicle analysis method and placental alkaline phosphatase (PLAP), a placenta-specific marker. RESULTS: The concentration of PEVs in pregnant women increased with the progression of gestational age, while the ratio of PEVs decreased to about 10% in the third trimester. Surprisingly, the PLAP+ EVs also presented in the plasma of non-pregnant women and normal male about 5%. The change in the ratio of PEVs can reflect the pregnancy status and also had a better diagnostic value in severe preeclampsia (AUC = 0.7811). CONCLUSIONS: Our study not only reveals the distribution pattern of PEVs, but also identifies the diagnostic potential of PEVs as biomarkers.

Rational N,P-Codoped pH-Activatable Red Carbon Dot for In Vitro and In Vivo Tumor Imaging.

Tumor detection and imaging via tumor microenvironmental indicators can have practical value. Here, a low-pH-responsive red carbon dot (CD) was prepared via a hydrothermal reaction for specific tumor imaging in vitro and in vivo. The probe responded to the acidic tumor microenvironment. The CDs are codoped by nitrogen and phosphorene and contain anilines on the surface. These anilines are efficient electron donors and modulate the pH response: Fluorescence is undetectable at common physical pH (>7.0), but red fluorescence (600-720 nm) increases with decreasing pH. The inactivation of fluorescence is due to three aspects: photoinduced electron transfer from anilines, deprotonation-induced energy states changing, and particle aggregation-induced quenching. It is believed that this pH-responsive character of CD is better than other reported CDs. Thus, in vitro images of HeLa cells show strong fluorescence that is 4-fold higher than normal cells. Subsequently, the CDs are used for in vivo imaging of tumors in mice. Tumors can be clearly observed within 1 h, and clearance of CDs will be finished within 24 h due to the small size of the CDs. The CDs offer excellent tumor-to-normal tissue (T/N) ratios and have great potential for biomedical research and disease diagnosis.