Dysregulated expression of miR-140 and miR-122 compromised microglial chemotaxis and led to reduced restriction of AD pathology.

BACKGROUND: Deposition of amyloid ß, which is produced by amyloidogenic cleavage of APP by ß- and γ-secretase, is one of the primary hallmarks of AD pathology. APP can also be processed by α- and γ-secretase sequentially, to generate sAPPα, which has been shown to be neuroprotective by promoting neurite outgrowth and neuronal survival, etc. METHODS: The global expression profiles of miRNA in blood plasma samples taken from 11 AD patients as well as from 14 age and sex matched cognitively normal volunteers were analyzed using miRNA-seq. Then, overexpressed miR-140 and miR-122 both in vivo and in vitro, and knock-down of the endogenous expression of miR-140 and miR-122 in vitro. Used a combination of techniques, including molecular biology, immunohistochemistry, to detect the impact of miRNAs on AD pathology. RESULTS: In this study, we identified that two miRNAs, miR-140-3p and miR-122-5p, both targeting ADAM10, the main α-secretase in CNS, were upregulated in the blood plasma of AD patients. Overexpression of these two miRNAs in mouse brains induced cognitive decline in wild type C57BL/6J mice as well as exacerbated dyscognition in APP/PS1 mice. Although significant changes in APP and total Aß were not detected, significantly downregulated ADAM10 and its non-amyloidogenic product, sAPPα, were observed in the mouse brains overexpressing miR-140/miR-122. Immunohistology analysis revealed increased neurite dystrophy that correlated with the reduced microglial chemotaxis in the hippocampi of these mice, independent of the other two ADAM10 substrates (neuronal CX3CL1 and microglial TREM2) that were involved in regulating the microglial immunoactivity. Further in vitro analysis demonstrated that both the reduced neuritic outgrowth of mouse embryonic neuronal cells overexpressing miR-140/miR-122 and the reduced Aß phagocytosis in microglia cells co-cultured with HT22 cells overexpressing miR-140/miR-122 could be rescued by overexpressing the specific inhibitory sequence of miR-140/miR-122 TuD as well as by addition of sAPPα, rendering these miRNAs as potential therapeutic targets. CONCLUSIONS: Our results suggested that neuroprotective sAPPα was a key player in the neuropathological progression induced by dysregulated expression of miR-140 and miR-122. Targeting these miRNAs might serve as a promising therapeutic strategy in AD treatment.

Which one is the best in treating deep venous thrombosis -- percutaneous mechanical thrombectomy, catheter-directed thrombolysis or combination of them?

OBJECTIVE: To compare the treatment outcomes among percutaneous mechanical thrombectomy (PMT) with AngioJet, Catheter-directed thrombolysis (CDT), and a combination of both. METHODS: One hundred forty nine patients with acute or sub-acute iliac-femoral vein thrombosis accepting CDT and/or PMT were divided into three groups respectively: PMT group, CDT group, PMT + CDT group (PMT followed by CDT). The severity of thrombosis was evaluated by venographic scoring system. Technical success was defined as restored patent deep venous blood flow after CDT and/or PMT. Clinical follow-up were assessed by ultrasound or venography imaging. The primary endpoints were recurrence of DVT, and severity level of post-thrombotic syndrome (PTS) during the follow-up. RESULTS: Technical success and immediate clinical improvements were achieved on all patients. The proportion of sub-acute DVT and the venographic scoring in PMT + CDT group were significantly higher than that in CDT group and PMT group (proportion of sub-acute DVT: p = 0.032 and p = 0.005, respectively; venographic scoring: p < 0.001, respectively). The proportion of May-Thurner Syndrome was lower in PMT group than that in CDT and PMT + CDT group (p = 0.026 and p = 0.005, respectively). The proportion of DVT recurrence/stent thrombosis was significantly higher in CDT group than that in PMT + CDT group (p = 0.04). The severity of PTS was the highest in CDT group ( χ2 = 14.459, p = 0.006) compared to PMT group (p = 0.029) and PMT + CDT group (p = 0.006). CONCLUSION: Patients with sub-acute DVT, high SVS scoring and combined May-Thurner Syndrome were recommended to take PMT + CDT treatment and might have lower rate of DVT recurrence/stent thrombosis and severe PTS. Our study provided evidence detailing of PMT + CDT therapy.

Enhanced quantum state transfer by circumventing quantum chaotic behavior.

The ability to realize high-fidelity quantum communication is one of the many facets required to build generic quantum computing devices. In addition to quantum processing, sensing, and storage, transferring the resulting quantum states demands a careful design that finds no parallel in classical communication. Existing experimental demonstrations of quantum information transfer in solid-state quantum systems are largely confined to small chains with few qubits, often relying upon non-generic schemes. Here, by using a superconducting quantum circuit featuring thirty-six tunable qubits, accompanied by general optimization procedures deeply rooted in overcoming quantum chaotic behavior, we demonstrate a scalable protocol for transferring few-particle quantum states in a two-dimensional quantum network. These include single-qubit excitation, two-qubit entangled states, and two excitations for which many-body effects are present. Our approach, combined with the quantum circuit's versatility, paves the way to short-distance quantum communication for connecting distributed quantum processors or registers, even if hampered by inherent imperfections in actual quantum devices.

Causal relationships of gut microbiota, plasma metabolites, and metabolite ratios with diffuse large B-cell lymphoma: a Mendelian randomization study.

Background: Recent studies have revealed changes in microbiota constitution and metabolites associated with tumor progression, however, no causal relation between microbiota or metabolites and diffuse large B-cell lymphoma (DLBCL) has yet been reported. Methods: We download a microbiota dataset from the MiBioGen study, a metabolites dataset from the Canadian Longitudinal Study on Aging (CLSA) study, and a DLBCL dataset from Integrative Epidemiology Unit Open genome-wide association study (GWAS) project. Mendelian randomization (MR) analysis was conducted using the R packages, TwoSampleMR and MR-PRESSO. Five MR methods were used: MR-Egger, inverse variance weighting (IVW), weighted median, simple mode, and weighted mode. Reverse MR analyses were also conducted to explore the causal effects of DLBCL on the microbiome, metabolites, and metabolite ratios. Pleiotropy was evaluated by MR Egger regression and MR-PRESSO global analyses, heterogeneity was assessed by Cochran's Q-test, and stability analyzed using the leave-one-out method. Results: 119 microorganisms, 1,091 plasma metabolite, and 309 metabolite ratios were analyzed. According to IVW analysis, five microorganisms were associated with risk of DLBCL. The genera Terrisporobacter (OR: 3.431, p = 0.049) andgenera Oscillibacter (OR: 2.406, p = 0.029) were associated with higher risk of DLBCL. Further, 27 plasma metabolites were identified as having a significant causal relationships with DLBCL, among which citrate levels had the most significant protective causal effect against DLBCL (p = 0.006), while glycosyl-N-tricosanoyl-sphingadienine levels was related to higher risk of DLBCL (p = 0.003). In addition, we identified 19 metabolite ratios with significant causal relationships to DLBCL, of which taurine/glutamate ratio had the most significant protective causal effect (p = 0.005), while the phosphoethanolamine/choline ratio was related to higher risk of DLBCL (p = 0.009). Reverse MR analysis did not reveal any significant causal influence of DLBCL on the above microbiota, metabolites, and metabolite ratios (p > 0.05). Sensitivity analyses revealed no significant heterogeneity or pleiotropy (p > 0.05). Conclusion: We present the first elucidation of the causal influence of microbiota and metabolites on DLBCL using MR methods, providing novel insights for potential targeting of specific microbiota or metabolites to prevent, assist in diagnosis, and treat DLBCL.

Melatonin modulates neuroinflammatory response and microglial activation in mice exposed to dim blue light at night.

Objectives: Dim light at night contributes to neurodegenerative diseases by causing neuroinflammation. In the central nervous system, the activation of microglia is a significant contributor to neuroinflammation. Therefore, there is an urgent need to find an intervention to treat the neuroinflammatory response caused by dim light at night. Melatonin is a rhythmic hormone whose synthesis is suppressed during the day. In this study, we attempt to explore whether and how melatonin improves hippocampal neuroinflammation in mice exposed to dim blue light at night. Materials and Methods: In vivo, a total of 36 male C57BL6/J mice that exposed to no light at night, dim blue light at night, and dim blue light at night with melatonin treatment. In vitro, the corticosterone-induced BV2 cells with or without melatonin treatment were used. Results: Both in vivo and in vitro experiments showed melatonin treatment significantly reduced dim blue light -induced hippocampal microglial activation and the expression of inflammatory factors IL-1ß and TNF-α. This improved effect of melatonin is related to its receptor MT2 rather than MT1. The MT2 blockers significantly increased mRNA levels of M1-type activation marker CD86 and inflammatory cytokines IL-1ß and TNF-α in melatonin-treated BV2 cells. Binding of melatonin to its receptor MT2 downregulated the expression of inflammatory proteins P-P65 and NLRP3, consequently inhibited the CD80 expression and M1-type activation in microglia. Furthermore, consistent with the decrease in microglial activation and inflammatory response after melatonin treatment, we also observed a reduction in hippocampal neuron loss and damage to the HT22 cells. Conclusion: Our findings suggested that melatonin may regulate microglial polarization through MT2/NF-kB-NLRP3 pathway and improves dim blue light -induced hippocampal neuroinflammation in mice.

Efficient solar-driven CO2-to-fuel conversion via Ni/MgAlO x @SiO2 nanocomposites at low temperature.

Solar-driven CO2-to-fuel conversion assisted by another major greenhouse gas CH4 is promising to concurrently tackle energy shortage and global warming problems. However, current techniques still suffer from drawbacks of low efficiency, poor stability, and low selectivity. Here, a novel nanocomposite composed of interconnected Ni/MgAlO x nanoflakes grown on SiO2 particles with excellent spatial confinement of active sites is proposed for direct solar-driven CO2-to-fuel conversion. An ultrahigh light-to-fuel efficiency up to 35.7%, high production rates of H2 (136.6 mmol min-1g- 1) and CO (148.2 mmol min-1g-1), excellent selectivity (H2/CO ratio of 0.92), and good stability are reported simultaneously. These outstanding performances are attributed to strong metal-support interactions, improved CO2 absorption and activation, and decreased apparent activation energy under direct light illumination. MgAlO x @SiO2 support helps to lower the activation energy of CH* oxidation to CHO* and improve the dissociation of CH4 to CH3* as confirmed by DFT calculations. Moreover, the lattice oxygen of MgAlO x participates in the reaction and contributes to the removal of carbon deposition. This work provides promising routes for the conversion of greenhouse gasses into industrially valuable syngas with high efficiency, high selectivity, and benign sustainability.

Environment consistently impact on aquaculture: The predominant source of residual pollutants in cultured Chinese mitten crab (Eriocheir sinensis) across China.

Advancements in monitoring and operation of aquaculture environments has minimized the concentrations of some residual pollutants in cultured aquatic products. However, currently most aquatic products are "farmed", and relationships among residual pollutants in tissues of crabs were still unclear. In this study, 64 typical pollutants, including 25 antibiotics, 15 metal, 23 organochlorine pesticides, and one dioxin-like compound inducing hydrocarbon-receptor (AHR) activity were measured in Chinese mitten crab (Eriocheir Sinensis) risks of consumption assessed and ranked. The superposition of properties including severity and relative potency of effects and parameters describing persistence and exposure along with rates of usage and identification of groups most likely to be exposed were assessed in combination to rank likelihood of dietary exposure and probabilities of adverse effects for each contaminant. The results indicated that the total scores per pollutants found that Cadmium (Cd), Heptachlor epoxide (HEPE), dioxin TEQ exhibited the greatest scores and explained the severity of dietary risk, while source analysis found that the three main pollutants resulted from the ambient environment and are not due to specific aquaculture processes. In summary, environment is still the predominant source of residual pollutants in cultured Chinese mitten crab across China.

Comparison of postoperative outcomes between endoscopy assisted minimal invasive direct anterior approach and bikini direct anterior approach in total hip arthroplasty.

BACKGROUND: We have innovatively developed a modified bikini direct anterior approach total hip arthroplasty (THA), endoscopy assisted minimal invasive direct anterior approach (Endo-DAA). The study compared aesthetic appearance of the scar, postoperative radiographic and functional outcomes, and complications of Endo-DAA with Bikini-DAA. METHODS: Patients who underwent primary THA using Endo-DAA or Bikini-DAA were included. The main innovation of Endo-DAA is the use of minimally invasive 5-7 cm proximal transverse incision and distal puncture with an endoscopy assisted split-type tool to complete the acetabular preparation and prosthesis implantation. Outcomes evaluated included evaluation of scar satisfaction, hip reconstruction including inclination, anteversion and leg-length discrepancy (LLD) and patient-reported outcomes including Harris Hip Scores (HHS) and Forgotten Joint Score (FJS). Follow-up time points included preoperative, 6 weeks, 6 months and 12 months. RESULTS: Finally, 195 hips in Endo-DAA and 207 hips in Bikini DAA completed the follow-up. The Endo-DAA group was superior to the Bikini-DAA group in the cosmetic aspects of scars. the cup anteversion angle of Endo-DAA group was significantly better than that in the Bikini-DAA group. The early HHS and FJS of the Endo-DAA group were superior to those of the Bikini-group. Operation time, blood loss, incision length, length of stay and duration to start no-assistive-device walking were also significantly better in the Endo-DAA group. Furthermore, the Bikini-DAA group had a higher incidence of complication. CONCLUSION: Compared with Bikini-incision, Endo-DAA improves patients' subjective satisfaction with scar aesthetics, accelerates rapid recovery of postoperative function, and reduces postoperative complications.

Antibiotics and polycyclic aromatic hydrocarbons in marine food webs of the Yellow River Estuary: Occurrence, trophic transfer, and human health risks.

Antibiotics and polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants in the aquatic region encompassing the estuary of the Yellow River and Laizhou Bay. But little information is available about the trophic transfer of antibiotics and PAHs in the marine food web of this area. This study investigated the occurrence and trophic transfer of 19 antibiotics and 16 PAHs in marine organisms from a food web of Laizhou Bay of the Yellow River estuary. Sulfonamides, fluoroquinolones, and 2 to 4-ring PAHs were the dominant contaminants in organisms. There was a significant positive correlation between the log total concentration of sulfonamides and trophic level (TL). Sulfadiazine, sulfamethazine, and erythromycin had biomagnification effects, while ciprofloxacin and ofloxacin had biological dilution effects. The log total concentration of PAHs had a significant negative correlation with TL. Naphthalene, fluorene, anthracene, pyrene, and benzo[g,h,i]perylene had biological dilution effects. The distinct correlations of trophic magnification factors Dow of antibiotics and Kow of 2 to 5-ring PAHs, indicating that the potential of these two coefficients for predicting their transfer. Risk assessment indicated that the consumption of seafood containing antibiotics and PAHs in Laizhou Bay of the Yellow River estuary posed health and carcinogenic risks to human, respectively.

Advances in microbial community, mechanisms and stimulation effects of direct interspecies electron transfer in anaerobic digestion.

Anaerobic digestion (AD) has been proven to be an effective green technology for producing biomethane while reducing environmental pollution. The interspecies electron transfer (IET) processes in AD are critical for acetogenesis and methanogenesis, and these IET processes are carried out via mediated interspecies electron transfer (MIET) and direct interspecies electron transfer (DIET). The latter has recently become a topic of significant interest, considering its potential to allow diffusion-free electron transfer during the AD process steps. To date, different multi-heme c-type cytochromes, electrically conductive pili (e-pili), and other relevant accessories during DIET between microorganisms of different natures have been reported. Additionally, several studies have been carried out on metagenomics and metatranscriptomics for better detection of DIET, the role of DIET's stimulation in alleviating stressed conditions, such as high organic loading rates (OLR) and lower pH, and the stimulation mechanisms of DIET in mixed cultures and co-cultures by various conductive materials. Keeping in view this significant research progress, this study provides in-depth insights into the DIET-active microbial community, DIET mechanisms of different species, utilization of various approaches for stimulating DIET, characterization approaches for effectively detecting DIET, and potential future research directions. All these can help accelerate the field's research progress, enable a better understanding of DIET in complex microbial communities, and allow its utilization to alleviate various inhibitions in complex AD processes.

A single-center, retrospective study of hospitalized patients with lower respiratory tract infections: clinical assessment of metagenomic next-generation sequencing and identification of risk factors in patients.

INTRODUCTION: Lower respiratory tract infections(LRTIs) in adults are complicated by diverse pathogens that challenge traditional detection methods, which are often slow and insensitive. Metagenomic next-generation sequencing (mNGS) offers a comprehensive, high-throughput, and unbiased approach to pathogen identification. This retrospective study evaluates the diagnostic efficacy of mNGS compared to conventional microbiological testing (CMT) in LRTIs, aiming to enhance detection accuracy and enable early clinical prediction. METHODS: In our retrospective single-center analysis, 451 patients with suspected LRTIs underwent mNGS testing from July 2020 to July 2023. We assessed the pathogen spectrum and compared the diagnostic efficacy of mNGS to CMT, with clinical comprehensive diagnosis serving as the reference standard. The study analyzed mNGS performance in lung tissue biopsies and bronchoalveolar lavage fluid (BALF) from cases suspected of lung infection. Patients were stratified into two groups based on clinical outcomes (improvement or mortality), and we compared clinical data and conventional laboratory indices between groups. A predictive model and nomogram for the prognosis of LRTIs were constructed using univariate followed by multivariate logistic regression, with model predictive accuracy evaluated by the area under the ROC curve (AUC). RESULTS: (1) Comparative Analysis of mNGS versus CMT: In a comprehensive analysis of 510 specimens, where 59 cases were concurrently collected from lung tissue biopsies and BALF, the study highlights the diagnostic superiority of mNGS over CMT. Specifically, mNGS demonstrated significantly higher sensitivity and specificity in BALF samples (82.86% vs. 44.42% and 52.00% vs. 21.05%, respectively, p < 0.001) alongside greater positive and negative predictive values (96.71% vs. 79.55% and 15.12% vs. 5.19%, respectively, p < 0.01). Additionally, when comparing simultaneous testing of lung tissue biopsies and BALF, mNGS showed enhanced sensitivity in BALF (84.21% vs. 57.41%), whereas lung tissues offered higher specificity (80.00% vs. 50.00%). (2) Analysis of Infectious Species in Patients from This Study: The study also notes a concerning incidence of lung abscesses and identifies Epstein-Barr virus (EBV), Fusobacterium nucleatum, Mycoplasma pneumoniae, Chlamydia psittaci, and Haemophilus influenzae as the most common pathogens, with Klebsiella pneumoniae emerging as the predominant bacterial culprit. Among herpes viruses, EBV and herpes virus 7 (HHV-7) were most frequently detected, with HHV-7 more prevalent in immunocompromised individuals. (3) Risk Factors for Adverse Prognosis and a Mortality Risk Prediction Model in Patients with LRTIs: We identified key risk factors for poor prognosis in lower respiratory tract infection patients, with significant findings including delayed time to mNGS testing, low lymphocyte percentage, presence of chronic lung disease, multiple comorbidities, false-negative CMT results, and positive herpesvirus affecting patient outcomes. We also developed a nomogram model with good consistency and high accuracy (AUC of 0.825) for predicting mortality risk in these patients, offering a valuable clinical tool for assessing prognosis. CONCLUSION: The study underscores mNGS as a superior tool for lower respiratory tract infection diagnosis, exhibiting higher sensitivity and specificity than traditional methods.

Neurotoxic mechanisms of mycotoxins: Focus on aflatoxin B1 and T-2 toxin.

Aflatoxin B1 (AFB1) and T-2 toxin are commonly found in animal feed and stored grain, posing a serious threat to human and animal health. Mycotoxins can penetrate brain tissue by compromising the blood-brain barrier, triggering oxidative stress and neuroinflammation, and leading to oxidative damage and apoptosis of brain cells. The potential neurotoxic mechanisms of AFB1 and T-2 toxin were discussed by summarizing the relevant research reports from the past ten years. AFB1 and T-2 toxin cause neuronal damage in the cerebral cortex and hippocampus, leading to synaptic transmission dysfunction, ultimately impairing the nervous system function of the body. The toxic mechanism is related to excessive reactive oxygen species (ROS), oxidative stress, mitochondrial dysfunction, apoptosis, autophagy, and an exaggerated inflammatory response. After passing through the blood-brain barrier, toxins can directly affect glial cells, alter the activation state of microglia and astrocytes, thereby promoting brain inflammation, disrupting the blood-brain barrier, and influencing the synaptic transmission process. We discussed the diverse effects of various concentrations of toxins and different modes of exposure on neurotoxicity. In addition, toxins can also cross the placental barrier, causing neurotoxic symptoms in offspring, as demonstrated in various species. Our goal is to uncover the underlying mechanisms of the neurotoxicity of AFB1 and T-2 toxin and to provide insights for future research, including investigating the impact of mycotoxins on interactions between microglia and astrocytes.

Immunomodulation Pathogenesis and Treatment of Bone Nonunion.

Fractures and bone nonunion commonly require surgical intervention. Serious outcomes of non-healing in the late stages of fracture place a significant financial burden on society and families. Bone nonunion occurs when a fracture stops healing, for many reasons, and leads to a variety of bad outcomes. Numerous factors, including biomechanics and immunology, are involved in the complicated mechanisms of bone nonunion. The immune-inflammatory response plays a significant part in the emergence of bone nonunion, and the occurrence, control, and remission of inflammation in the bone healing process have a significant influence on the ultimate success of bone tissue repair. In the bone microenvironment, immune cells and associated cytokines control bone repair, which is significantly influenced by macrophages, T cells, and fibroblast growth factor. To limit acute inflammation and  balance osteogenesis and osteoblastogenesis for tissue repair and regeneration, immune cells and various cytokines in the local microenvironment must be precisely regulated. As a bad complication of late-stage fractures, bone nonunion has a significant effect on patients' quality of life and socioeconomic development. Therefore, in-depth research on its pathogenesis and treatment methods has important clinical value. To provide more precise, focused therapeutic options for the treatment of bone nonunion, we discuss the regulatory roles of the key immune cells engaged in bone healing within the microenvironment during bone healing and their effect on osteogenesis.

Responses of Digestive, Antioxidant, Immunological and Metabolic Enzymes in the Intestines and Liver of Largemouth Bass (Micropterus salmoides) under the Biofloc Model.

To investigate the activities of intestinal digestive enzymes, liver antioxidant enzymes, immunological enzymes, and glucometabolic enzymes in largemouth bass (Micropterus salmoides) under the biofloc model, an experiment was conducted in 300-liter glass tanks. The experiment comprised a control group, which was fed a basal diet, and a biofloc group, where glucose was added to maintain a C/N ratio of 15. Each group had three parallel setups, with a stocking density of 20 fish per tank. The experiment ran for 60 days, employing a zero-water exchange aquaculture model. The results showed that at the end of the culture period, there were no significant differences between the initial weight, final weight, WGR, SGR, and SR of the biofloc group and the control group of largemouth bass (p > 0.05), whereas the lower FCR and the higher PER in the biofloc group were significant (p < 0.05); intestinal α-amylase, trypsin, and lipase activities of largemouth bass in the biofloc group were significantly increased by 37.20%, 64.11%, and 51.69%, respectively, compared with the control group (p < 0.05); liver superoxide dismutase and catalase activities, and total antioxidant capacity of largemouth bass in the biofloc group were significantly increased by 49.26%, 46.87%, and 98.94% (p < 0.05), while the malondialdehyde content was significantly reduced by 19.91% (p < 0.05); liver lysozyme, alkaline phosphatase, and acid phosphatase activities of largemouth bass in the biofloc group were significantly increased by 62.66%, 41.22%, and 29.66%, respectively (p < 0.05); liver glucokinase, pyruvate kinase, glucose-6-phosphate kinase, pyruvate kinase, glucose-6-phosphatase, and glycogen synthase activities were significantly increased by 46.29%, 99.33%, 32.54%, and 26.89%, respectively (p < 0.05). The study showed that the biofloc model of culturing largemouth bass can not only enhance digestive enzyme activities, antioxidant capacity, and immune response but can also promote the process of glucose metabolism and reduce feeding costs. This study provides data support for healthy culturing of largemouth bass in future production, provides a theoretical reference for optimizing the biofloc technology culture model, and is crucial for promoting the healthy and green development of aquaculture.

Noninvasive diagnosis of interstitial fibrosis in chronic kidney disease: a systematic review and meta-analysis.

RATIONALE AND OBJECTIVES: Researchers have delved into noninvasive diagnostic methods of renal fibrosis (RF) in chronic kidney disease, including ultrasound (US), magnetic resonance imaging (MRI), and radiomics. However, the value of these diagnostic methods in the noninvasive diagnosis of RF remains contentious. Consequently, the present study aimed to systematically delineate the accuracy of the noninvasive diagnosis of RF. MATERIALS AND METHODS: A systematic search covering PubMed, Embase, Cochrane Library, and Web of Science databases for all data available up to 28 July 2023 was conducted for eligible studies. RESULTS: We included 21 studies covering 4885 participants. Among them, nine studies utilized US as a noninvasive diagnostic method, eight studies used MRI, and four articles employed radiomics. The sensitivity and specificity of US for detecting RF were 0.81 (95% CI: 0.76-0.86) and 0.79 (95% CI: 0.72-0.84). The sensitivity and specificity of MRI were 0.77 (95% CI: 0.70-0.83) and 0.92 (95% CI: 0.85-0.96). The sensitivity and specificity of radiomics were 0.69 (95% CI: 0.59-0.77) and 0.78 (95% CI: 0.68-0.85). CONCLUSIONS: The current early noninvasive diagnostic methods for RF include US, MRI, and radiomics. However, this study demonstrates that US has a higher sensitivity for the detection of RF compared to MRI. Compared to US, radiomics studies based on US did not show superior advantages. Therefore, challenges still exist in the current radiomics approaches for diagnosing RF, and further exploration of optimized artificial intelligence (AI) algorithms and technologies is needed.

Deciphering the SOX4/MAPK1 regulatory axis: a phosphoproteomic insight into IQGAP1 phosphorylation and pancreatic Cancer progression.

OBJECTIVE: This study aims to elucidate the functional role of IQGAP1 phosphorylation modification mediated by the SOX4/MAPK1 regulatory axis in developing pancreatic cancer through phosphoproteomics analysis. METHODS: Proteomics and phosphoproteomics data of pancreatic cancer were obtained from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Differential analysis, kinase-substrate enrichment analysis (KSEA), and independent prognosis analysis were performed on these datasets. Subtype analysis of pancreatic cancer patients was conducted based on the expression of prognostic-related proteins, and the prognosis of different subtypes was evaluated through prognosis analysis. Differential analysis of proteins in different subtypes was performed to identify differential proteins in the high-risk subtype. Clinical correlation analysis was conducted based on the expression of prognostic-related proteins, pancreatic cancer typing results, and clinical characteristics in the pancreatic cancer proteomics dataset. Functional pathway enrichment analysis was performed using GSEA/GO/KEGG, and most module proteins correlated with pancreatic cancer were selected using WGCNA analysis. In cell experiments, pancreatic cancer cells were grouped, and the expression levels of SOX4, MAPK1, and the phosphorylation level of IQGAP1 were detected by RT-qPCR and Western blot experiments. The effect of SOX4 on MAPK1 promoter transcriptional activity was assessed using a dual-luciferase assay, and the enrichment of SOX4 on the MAPK1 promoter was examined using a ChIP assay. The proliferation, migration, and invasion functions of grouped pancreatic cancer cells were assessed using CCK-8, colony formation, and Transwell assays. In animal experiments, the impact of SOX4 on tumor growth and metastasis through the regulation of MAPK1-IQGAP1 phosphorylation modification was studied by constructing subcutaneous and orthotopic pancreatic cancer xenograft models, as well as a liver metastasis model in nude mice. RESULTS: Phosphoproteomics and proteomics data analysis revealed that the kinase MAPK1 may play an important role in pancreatic cancer progression by promoting IQGAP1 phosphorylation modification. Proteomics analysis classified pancreatic cancer patients into two subtypes, C1 and C2, where the high-risk C2 subtype was associated with poor prognosis, malignant tumor typing, and enriched tumor-related pathways. SOX4 may promote the occurrence of the high-risk C2 subtype of pancreatic cancer by regulating MAPK1-IQGAP1 phosphorylation modification. In vitro cell experiments confirmed that SOX4 promoted IQGAP1 phosphorylation modification by activating MAPK1 transcription while silencing SOX4 inhibited the proliferation, migration, and invasion of pancreatic cancer cells by reducing the phosphorylation level of MAPK1-IQGAP1. In vivo, animal experiments further confirmed that silencing SOX4 suppressed the growth and metastasis of pancreatic cancer by reducing the phosphorylation level of MAPK1-IQGAP1. CONCLUSION: The findings of this study suggest that SOX4 promotes the phosphorylation modification of IQGAP1 by activating MAPK1 transcription, thereby facilitating the growth and metastasis of pancreatic cancer.

Effects of 16.8-22.0 T high static magnetic fields on the development of zebrafish in early fertilization.

OBJECTIVES: Despite some existing studies on the safety of high static magnetic fields (SMFs), the effects of ultra-high SMFs above 20.0 T for embryonic development in early pregnancy are absent. The objective of this study is to evaluate the influence of 16.8-22.0 T SMF on the development of zebrafish embryos, which will provide important information for the future application of ultra-high field magnetic resonance imaging (MRI). METHODS: Two-hour exposure to homogenous (0 T/m) 22.0 T SMF, or 16.8 T SMFs with 123.25 T/m spatial gradient of opposite magnetic force directions was examined in the embryonic development of 200 zebrafish. Their body length, heart rate, spontaneous tail-wagging movement, hatching and survival rate, photomotor response, and visual motor response (VMR) were analyzed. RESULTS: Our results show that these ultra-high SMFs did not significantly affect the general development of zebrafish embryos, such as the body length or spontaneous tail-wagging movement. However, the hatching rate was reduced by the gradient SMFs (p < 0.05), but not the homogenous 22.0 T SMF. Moreover, although the zebrafish larva activities were differentially affected by these ultra-high SMFs (p < 0.05), the expression of several visual and neurodevelopmental genes (p < 0.05) was generally downregulated in the eyeball. CONCLUSIONS: Our findings suggest that exposure to ultra-high SMFs, especially the gradient SMFs, may have adverse effects on embryonic development, which should cause some attention to the future application of ultra-high field MRIs. CLINICAL RELEVANCE STATEMENT: As technology advances, it is conceivable that very strong magnetic fields may be adapted for use in medical imaging. Possible dangers associated with these higher Tesla fields need to be considered and evaluated prior to human use. KEY POINTS: Ultra-High static magnetic field may affect early embryonic development. High strength gradient static magnetic field exposure impacted zebrafish embryonic development. The application of very strong magnetic fields for MR technologies needs to be carefully evaluated.

Serum metabolomics study reveals a distinct metabolic diagnostic model for renal calculi.

Renal calculi (RC) represent a prevalent disease of the urinary system characterized by a high incidence rate. The traditional clinical diagnosis of RC emphasizes imaging and stone composition analysis. However, the significance of metabolic status in RC diagnosis and prevention remains unclear. This study aimed to investigate serum metabolites in RC patients to identify those associated with RC and to develop a metabolite-based diagnostic model. We employed nontargeted metabolomics utilizing ultra-performance liquid chromatography‒mass spectrometry (UPLC‒MS) to compare serum metabolites between RC patients and healthy controls. Our findings demonstrated significant disparities in serum metabolites, particularly in fatty acids and glycerophospholipids, between the two groups. Notably, the glycerophospholipid (GP) metabolic pathway in RC patients was significantly disrupted. Logistic regression models using differentially abundant metabolites revealed that elevated levels of 2-butyl-4-methyl phenol and reduced levels of phosphatidylethanolamine (P-16:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)) had the most substantial effect on RC risk. Overall, our study indicates that RC induces notable alterations in serum metabolites and that the diagnostic model based on these metabolites effectively distinguishes RC. This research offers promising insights and directions for further diagnostic and mechanistic studies on RC.

Citizen science in action: Time-resolved immunofluorescence-based field detection of antibiotics with portable analytical kit.

Citizen scientist-based environmental monitoring and public education are becoming increasingly popular. However, current technologies for antibiotic-based novel contaminant identification are still restricted to laboratory sample collection and analysis due to detection methodologies and apparatus limitations. This study developed a time-resolved immunofluorescence-based simultaneous field-based assay for ciprofloxacin (CIP) and enrofloxacin (ENR) that matches test results to geographic locations. The assay helps the public understand the potential levels of antibiotic exposures in their environments and helps them take appropriate action to reduce risk. The assay was developed using smartphones and social software in addition to rapid testing. The method uses a portable, low-cost analytical kit with a smartphone app to build a field-based detection platform for the detection and analysis of ENR and CIP in water and aquatic products. The methodological evaluation was good, with detection limits of 0.4 ng/mL and 0.5 ng/g for ENR in water and fish, and quantification limits of 1.2 ng/mL and 1.4 ng/g, with recoveries of 89.0 %-101.0 % and 78.0 %-97.0 %. For CIP in water and fish, the limits of detection were 0.3 ng/mL and 0.4 ng/g, the limits of quantification were 0.9 ng/mL and 1.2 ng/g, and the recoveries were 75.0 %-91.0 % and 72.0 %-89.0 %, both with coefficients of variation <15 %. These limits were sufficient to prevent the two antibiotics from crossing over during simultaneous detection. The assay was validated using real samples to assess the effectiveness of the assay platform in field deployments, and the results were consistent with those obtained through liquid chromatography-tandem mass spectrometry (LC-MS) and enzyme-linked immunoassay (ELISA) techniques. In addition, the TRFIA assay process requires less time, uses more portable instruments, and is less complex than traditional methods. This study provides a new scientific, accurate, and rapid detection method for antibiotic detection by citizen scientists, helping scientists to obtain a wider range of data and providing more opportunities to solve scientific problems.