PEI-Mediated Assembly of Fe3O4 onto SiO2-Encapsulated CsPbBr3 for Highly Sensitive Fluorescent Lateral Flow Immunoassay.

The conventional lateral flow immunoassay (LFIA) method using colloidal gold nanoparticles (Au NPs) as labeling agents faces two inherent limitations, including restricted sensitivity and poor quantitative capability, which impede early viral infection detection. Herein, we designed and synthesized CsPbBr3 perovskite quantum dot-based composite nanoparticles, CsPbBr3@SiO2@Fe3O4 (CSF), which integrated fluorescence detection and magnetic enrichment properties into LFIA technology and achieved rapid, sensitive, and convenient quantitative detection of the SARS-CoV-2 virus N protein. In this study, CsPbBr3 served as a high-quantum-yield fluorescent signaling probe, while SiO2 significantly enhanced the stability and biomodifiability of CsPbBr3. Importantly, the SiO2 shell shows relatively low absorption or scattering toward fluorescence, maintaining a quantum yield of up to 74.4% in CsPbBr3@SiO2. Assembly of Fe3O4 nanoparticles mediated by PEI further enhanced the method's sensitivity and reduced matrix interference through magnetic enrichment. Consequently, the method achieved a fluorescent detection range of 1 × 102 to 5 × 106 pg·mL-1 after magnetic enrichment, with a limit of detection (LOD) of 58.8 pg·mL-1, representing a 13.3-fold improvement compared to nonenriched samples (7.58 × 102 pg·mL-1) and a 2-orders-of-magnitude improvement over commercial colloidal gold kits. Furthermore, the method exhibited 80% positive and 100% negative detection rates in clinical samples. This approach holds promise for on-site diagnosis, home-based quantitative tests, and disease procession evaluation.

Development of radiofluorinated MLN-4760 derivatives for PET imaging of the SARS-CoV-2 entry receptor ACE2.

PURPOSE: The angiotensin converting enzyme 2 (ACE2) plays a regulatory role in the cardiovascular system and serves SARS-CoV-2 as an entry receptor. The aim of this study was to synthesize and evaluate radiofluorinated derivatives of the ACE2 inhibitor MLN-4760. [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 were demonstrated to be suitable for non-invasive imaging of ACE2, potentially enabling a better understanding of its expression dynamics. METHODS: Computational molecular modeling, based on the structures of human ACE2 (hACE2) and mouse ACE2 (mACE2), revealed that the ACE2-binding modes of F-MLN-4760 and F-Aza-MLN-4760 were similar to that of MLN-4760. Co-crystallization of the hACE2/F-MLN-4760 protein complex was performed for confirmation. Displacement experiments using [3H]MLN-4760 enabled the determination of the binding affinities of the synthesized F-MLN-4760 and F-Aza-MLN-4760 to hACE2 expressed in HEK-ACE2 cells. Aryl trimethylstannane-based and pyridine-based radiofluorination precursors were synthesized and used for the preparation of the respective radiotracers. [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 were evaluated with regard to the uptake in HEK-ACE2 and HEK-ACE cells and in vitro binding to tissue sections of HEK-ACE2 xenografts and normal organs of mice. Biodistribution and PET/CT imaging studies of [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 were performed using HEK-ACE2 and HEK-ACE xenografted nude mice. RESULTS: Crystallography data revealed an equal hACE2-binding mode for F-MLN-4760 as previously found for MLN-4760. Moreover, computer-based modeling indicated that similar binding to hACE2 and mACE2 holds true for both, F-MLN-4760 and F-Aza-MLN-4760, as is the case for MLN-4760. The IC50 values were three-fold and seven-fold higher for F-MLN-4760 and F-Aza-MLN-4760, respectively, than for MLN-4760. [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 were obtained in 1.4 ± 0.3 GBq and 0.5 ± 0.1 GBq activity with > 99% radiochemical purity in a 5.3% and 1.2% radiochemical yield, respectively. Uptake in HEK-ACE2 cells was higher for [18F]F-MLN-4760 (67 ± 9%) than for [18F]F-Aza-MLN-4760 (37 ± 8%) after 3-h incubation while negligible uptake was seen in HEK-ACE cells (< 0.3%). [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 accumulated specifically in HEK-ACE2 xenografts of mice (13 ± 2% IA/g and 15 ± 2% IA/g at 1 h p.i.) with almost no uptake observed in HEK-ACE xenografts (< 0.3% IA/g). This was confirmed by PET/CT imaging, which also visualized unspecific accumulation in the gall bladder and intestinal tract. CONCLUSION: Both radiotracers showed specific and selective binding to ACE2 in vitro and in vivo. [18F]F-MLN-4760 was, however, obtained in higher yields and the ACE2-binding affinity was superior over that of [18F]F-Aza-MLN-4760. [18F]F-MLN-4760 would, thus, be the candidate of choice for further development in view of its use for PET imaging of ACE2.

Improvement of TaC9-ABE mediated correction of human SMN2 gene.

Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Gene editing technology repairs the conversion of the 6th base T to C in exon 7 of the paralogous SMN2 gene, compensating for the SMN protein expression and promoting the survival and function of motor neurons. However, low editing efficiency and unintended off-target effects limit the application of this technology. Here, we optimized a TaC9-adenine base editor (ABE) system by combining Cas9 nickase with the transcription activator-like effector (TALE)-adenosine deaminase fusion protein to effectively and precisely edit SMN2 without detectable Cas9 dependent off-target effects in human cell lines. We also generated human SMA-induced pluripotent stem cells (SMA-iPSCs) through the mutation of the splice acceptor or deletion of the exon 7 of SMN1. TaC9-R10 induced 45% SMN2 T6 > C conversion in the SMA-iPSCs. The SMN2 T6 > C splice-corrected SMA-iPSCs were directionally differentiated into motor neurons, exhibiting SMN protein recovery and antiapoptosis ability. Therefore, the TaC9-ABE system with dual guides from the combination of Cas9 with TALE could be a potential therapeutic strategy for SMA with high efficacy and safety.

Two {CuI[P4Mo6]2}-Based Coordination Polymers Incorporating In Situ Converted Tetrapyridyl Ligands for Trace Analysis of Nitrofuran Antibiotics.

Nitrofurans are important synthetic broad-spectrum antibacterial drugs with the basic structure of 5-nitrofuran. Due to their toxicity, it is essential to develop a sensitive sensor with strong anti-interference capabilities for their detection. In this work, two {P4Mo6O31}12--based compounds, [H4(HPTTP)]2{CuI[Mo12O24(OH)6(PO4)3(HPO4)(H2PO4)4]}·xH2O (x = 13 for (1), 7 for (2); HPTTP = 4,4',4″,4‴-(1H-pyrrole-2,3,4,5-tetrayl)tetrapyridine), exhibiting similar coordination but distinct stacking modes. Both compounds were synthesized and used for the electrochemical detection of nitrofuran antibiotics. The tetrapyridine-based ligand was generated in situ during assembly, and its potential mechanism was discussed. Composite electrode materials, formed by mixing graphite powder with compounds 1-2 and physically grinding them, proved to be highly effective in the electrochemical trace detection of furazolidone (FZD) and furaltadone hydrochloride (FTD·HCl) under optimal conditions. Besides, the possible electrochemical detection mechanisms of two nitro-antibiotics were studied.

Effect of citric acid on cell membrane structure and function of Issatchenkia terricola WJL-G4.

AIMS: This study aimed to investigate the changes of cell membrane structure and function of Issatchenkia terricola under citric acid by performing physiological analysis. METHODS AND RESULTS: The membrane integrity, surface hydrophobicity, structure, fluidity, apoptosis, and fatty acid methyl esters composition of I. terricola WJL-G4 cells were determined by propidium iodide staining, microbial adhesion to hydrocarbon test, transmission electron microscopy analysis, fluorescence anisotropy, flow cytometry, and gas chromatography-mass, respectively. The results showed that with the increasing of citric acid concentrations, the cell vitality, membrane integrity, and fluidity of I. terricola reduced; meanwhile, apoptosis rate, membrane permeable, hydrophobicity, and ergosterol contents augmented significantly. Compared to control, the activities of Na+, K+-ATPase, and Ca2+, Mg2+-ATPase increased by 3.73-fold and 6.70-fold, respectively, when citric acid concentration increased to 20 g l-1. The cells cracked and their cytoplasm effused when the citric acid concentration reached 80 g l-1. CONCLUSIONS: I. terricola could successfully adjust its membrane structure and function below 60 g l-1 of citric acid. However, for citric acid concentrations above 80 g l-1, its structure and function were dramatically changed, which might result in reduced functionality.

Improved Precision and Safety of Supra-Tentorial Intracranial Hematoma Puncture Using C-Arm CT Four-Dimensional Navigation.

BACKGROUND Spontaneous intracerebral hemorrhage has a high fatality rate within the initial month after onset. This study determined the safety and therapeutic efficacy of minimally invasive puncture for supra-tentorial intracranial hematoma under C-arm computed tomography (CT) 4-dimensional navigation. MATERIAL AND METHODS We retrospectively analyzed 64 patients with supra-tentorial cerebral hemorrhage from June 2020 to May 2023; 31 patients were assigned to the study group (C-arm CT navigation puncture) and 33 patients were in the control group (conventional CT-guided puncture). The analysis focused on assessment of puncture error, postoperative complication rate, and the Glasgow Outcome Scale (GOS) and National Institute of Health Stroke Scale (NIHSS) scores 30 and 90 days after surgery. RESULTS C-arm CT navigation puncture had improved precision, with significantly reduced transverse (3.17±1.75 mm) and longitudinal (1.83±1.21 mm) deviations, compared with the control group (7.88±1.74 mm and 5.50±1.84 mm, respectively; P<0.05). The overall postoperative complication rate was significantly lower in the study group than in the control group (12.90% vs 36.36%, P<0.05). The mean GOS score was higher in the study group than in the control group 30 and 90 days postoperatively (3.42±0.96 and 3.97±0.95 vs 2.94±0.79 and 3.46±0.90, respectively; P<0.05), while the mean NIHSS score was lower in the study group than in the control group 30 and 90 days postoperatively (10.58±6.52 and 5.97±4.55 vs 14.42±8.13 and 9.55±8.31, respectively; P<0.05). CONCLUSIONS Supra-tentorial intracranial hematoma puncture under C-arm CT 4-dimensional navigation is accurate, safe, and beneficial.

A highly sensitive point-of-care detection platform for Salmonella typhimurium by integrating magnetic enrichment and fluorescent CsPbBr3@SiO2.

A platform was designed based on Fe3O4 and CsPbBr3@SiO2 for integrated magnetic enrichment-fluorescence detection of Salmonella typhimurium, which significantly simplifies the detection process and enhances the working efficiency. Fe3O4 served as a magnetic enrichment unit for the capture of S. typhimurium. CsPbBr3@SiO2 was employed as a fluorescence-sensing unit for quantitative signal output, where SiO2 was introduced to strengthen the stability of CsPbBr3, improve its biomodificability, and prevent lead leakage. More importantly, the SiO2 shell shows neglectable absorption or scattering towards fluorescence, making the CsPbBr3@SiO2 exhibit a high quantum yield of 74.4%. After magnetic enrichment, the decreasing rate of the fluorescence emission intensity of the CsPbBr3@SiO2 supernatant at 527 nm under excitation light at UV 365 nm showed a strong linear correlation with S. typhimurium concentration of 1 × 102~1 × 108 CFU∙mL-1, and the limit of detection (LOD) reached 12.72 CFU∙mL-1. This platform has demonstrated outstanding stability, reproducibility, and resistance to interference, which provides an alternative for convenient and quantitative detection of S. typhimurium.

Effects of understory intercropping with salt-tolerant legumes on soil organic carbon pool in coastal saline-alkali land.

Phytoremediation through understory intercropping with salt-tolerant legumes (forest-green manure composite patterns) efficiently and sustainably enhances saline-alkali soils, while significantly improving the stability of monoculture forest ecosystems and the efficacy of soil upgrades. However, exactly how forest-green manure patterns regulate the dynamics of the soil organic carbon (SOC) pool and related mechanisms remain unclear. For this study, a pure forest was used as the control, and three leguminous herbaceous plants (M. sativa, S. cannabina, and C. pallida) were intercropped under two forest stand types (T. hybrid 'Zhongshanshan' and C. illinoensis). The variable characteristics and control factors of SOC and its components under different patterns were elucidated by analyzing the soil physical and chemical properties, enzyme activities, and microbial communities. The results revealed that the composite pattern improved soil salinization and increased the activities of ß-1,4-glucosidase, polyphenol oxidase, peroxidase (PER), invertase (INV), and urease, as well as the carbon pool management index and the proportion of active organic carbon. At the T. hybrid 'Zhongshanshan' experimental site, planting M. sativa effectively increased the total carbon (TC) content. The ammonium nitrogen, soil moisture content, total phosphorus, alkaline phosphatase, PER, and polyphenol oxidase were the primary driving factors that affected the SOC pool. At the C. illinoensis experimental site, S. cannabina planting was observed to increase the TC content, with the TC, exchangeable Na+, ß-1,4-N-acetylglucosaminidase, and INV being the main driving factors that impacted the SOC pool. The composite pattern can indirectly influence the SOC pool by altering the soil properties to regulate the microbial community. Further, it was found that soil inorganic carbon (SIC) was the main contributor to increasing the soil carbon pool following the short-term planting of legumes; thus, there may have been a transfer process that occurred from the SOC to SIC. Our study suggests that the forest-green manure pattern has more positive effects on improving soil quality and the carbon pool in saline-alkali land.

Effects of an inoculation dose of Issatchenkia terricola WJL-G4 on physicochemical properties, active substances, and antioxidant capacity of black, red, and white currant juice.

BACKGROUND: Due to the high level of organic acids - primarily citric acid - black, red, and white currants have an excessively sour taste, making taste adjustment during processing challenging. This study investigated and evaluated the effects of an inoculation dose of the acid-reducing yeast Issatchenkia terricola WJL-G4 on several aspect such as physicochemical properties, chromaticity, active substances, and antioxidant capacity. A sensory evaluation was also conducted. RESULTS: The results indicated that, when the inoculation dose increased from 2% to 12%, the total phenol, total flavonoid, and total anthocyanin content, and antioxidant capacity in currant juice decreased. A low inoculation dose (2-4%) was beneficial for preserving the total phenol and total flavonoid content. Although the levels of most phenolic compounds decreased, the concentrations of caffeic acid, p-coumaric acid, ferulic acid, rutin, and epicatechin were significantly higher than the control after fermentation. Overall acceptability and taste scores of fermented currants improved compared with those of the control group. CONCLUSION: This experiment provided an effective solution, with a theoretical basis, to the problems of the sour taste and harsh flavor of currant juice. © 2024 Society of Chemical Industry.

Fixed-Time Aperiodic Intermittent Control for Quasi-Bipartite Synchronization of Competitive Neural Networks.

This paper concerns a class of coupled competitive neural networks, subject to disturbance and discontinuous activation functions. To realize the fixed-time quasi-bipartite synchronization, an aperiodic intermittent controller is initially designed. Subsequently, by combining the fixed-time stability theory and nonsmooth analysis, several criteria are established to ensure the bipartite synchronization in fixed time. Moreover, synchronization error bounds and settling time estimates are provided. Finally, numerical simulations are presented to verify the main results.

Quantitative proteomic analysis of exosomes from umbilical cord mesenchymal stem cells and rat bone marrow stem cells.

Exosomes derived from mesenchymal stem cells (MSCs) have been used for cancer treatment, however, an in-depth analysis of the exosomal proteomes is lacking. In this manuscript, we use the diaPASEF (parallel accumulation serial fragmentation combined with the data-independent acquisition) method to quantify exosomes derived from human umbilical cord mesenchymal stem cells (UCMSCs) and rat bone marrow stem cells (BMSCs), resulting in identification of 4200 human proteins and 5362 rat proteins. Comparison of human exosomal proteins and total cellular proteins reveals that some proteins exist in the exosomes exclusively that can be served as potential markers for exosomes. Quantitative proteomic analysis of exosomes from different passages of BMSCs shows that the proteins involved in TGF-ß signaling pathway are regulated in abundance, which could be markers for the therapeutic ability of BMSC exosomes. Collectively, the data presented by this study can be a resource for further study of exosome research.

Long-term Outcomes of Ultrasound-guided Thermal Ablation for the Treatment of Solitary Low-risk Papillary Thyroid Microcarcinoma: A Multicenter Retrospective Study.

OBJECTIVE: To report more than 5-year outcomes of ultrasound-guided thermal ablation (TA) for patients with solitary low-risk papillary thyroid microcarcinoma (PTMC) in a large multicenter cohort. BACKGROUND: TA, including radiofrequency ablation (RFA) and microwave ablation (MWA) have been used in patients with low-risk PTMC who refuse surgery or active surveillance. However, its clinical value remains controversial. MATERIALS AND METHODS: This retrospective multicenter study included 474 patients with solitary low-risk PTMC treated with TA (357 for RFA; 117 for MWA) from 4 centers and followed up for at least 5 years. Disease progression including lymph node metastasis and recurrent tumors, volume reduction rate (VRR), tumor disappearance rate, complications, and delayed surgery were assessed. RFA and MWA outcomes were compared using propensity score matching. RESULTS: During the median follow-up period of 77.2 months, disease progression incidence, lymph node metastasis, and recurrent tumors rates were 3.6%, 1.1%, and 2.5%, respectively. Age below 40 years old, male sex, Hashimoto thyroiditis, and tumor size were not independent factors associated with disease progression by Cox analysis. The median VRR was 100% and 471 tumors disappeared radiographically. Eight patients experienced transient voice change (1.7%) which recovered within 3 months. None of the patients underwent delayed surgery because of anxiety. After 1:1 matching, no significant differences were found in the disease progression, VRR, tumor disappearance rate, or complications between RFA and MWA subgroups. CONCLUSION: This multicenter study revealed that TA was an effective and safe treatment for patients with solitary low-risk PTMC, which could be offered as a treatment option for the management for low-risk PTMC.

A Lipid Droplet-Specific NIR Fluorescent Probe with a Large Stokes Shift for In Vivo Visualization of Polarity in Contrast-Induced Acute Kidney Injury.

The research on lipid droplets (LDs) has attracted great attention in the field of biomedical science in recent years. LD malfunction is found to be associated with the development of acute kidney injury (AKI). To monitor this biological process and explain related pathological behavior, the development of excellent LD fluorescent probes with a polarity-sensitive character would provide a desirable strategy. Herein, we designed a new polarity-susceptible fluorescent probe named LD-B with LD targetability, which exhibits very weak fluorescence in highly polar solvents based on the twisted intramolecular charge transfer effect but enhanced fluorescence in low polar environments, enabling us to visualize polarity alteration. The probe LD-B also possesses the merits of intense near-infrared (NIR) emission, good photostability, large Stokes shift, low toxicity, faster metabolic rate, and wash-free ability; thereby, it would contribute to efficient LD fluorescence visualization application. Using LD-B via confocal laser scanning fluorescence imaging and a small-animal imaging system in vivo, we first manifested a prominent rise of LD polarity in contrast-induced AKI (CI-AKI), not only at the cellular level but also in animals in vivo. Furthermore, the in vivo studies suggest that LD-B could accumulate in the kidney. In addition, the normal cell lines (including kidney cells) exhibiting a greater polarity of LDs than the cancer cells have been demonstrated systemically. Altogether, our work presents an effective approach for the medical diagnosis of LDs related to CI-AKI and identification of potential therapeutic markers.

Urbanization in developing countries overrides catchment productivity in fueling inland water CO2 emissions.

We compiled a nationwide dataset of carbon dioxide (CO2 ) efflux from 1405 measurements, and found that lakes, reservoirs, and rivers emit a total of 61.9 ± 55.3 TgC as CO2 each year, corresponding to ~6.3% of the annual total national CO2 emission in 2020. Our analysis showed that the presence of anthropogenic disturbances in catchments strongly influences the emission of CO2 from these waters in the non-pristine areas, masking the catchment productivity effect on the emission of CO2 . Our results highlight the need for adjusting climate change models for taking into account anthropogenic effects on CO2 emissions from inland waters.

Prevalence and molecular characterization of Cryptosporidium spp. in dairy cattle in Central Inner Mongolia, Northern China.

BACKGROUND: Cryptosporidium is a gastrointestinal protozoan that widely exists in nature, it is an established zoonotic pathogen. Infected cattle are considered to be associated with cryptosporidiosis outbreaks in humans. In the present study, we aimed to assess the prevalence and species distribution of Cryptosporidium in dairy cattle in Central Inner Mongolia. METHODS: We focused on the small subunit ribosomal RNA gene (SSU rRNA) of Cryptosporidium and 60-kDa glycoprotein gene (gp60) of Cryptosporidium parvum. We collected 505 dairy cattle manure samples from 6 sampling sites in Inner Mongolia in 2021; the samples were divided into 4 groups based on age. DNA extraction, polymerase chain reaction (PCR), sequence analysis, and restriction fragment length polymorphism (RFLP) using SspI and MboII restriction endonucleases were performed. RFLP analysis was performed to determine the prevalence and species distribution of Cryptosporidium. RESULTS: SSU rRNA PCR revealed that the overall prevalence of Cryptosporidium infection was 29.90% (151/505), with a prevalence of 37.67% (55/146) and 26.74% (96/359) in diarrheal and nondiarrheal samples, respectively; these differences were significant. The overall prevalence of Cryptosporidium infection at the 6 sampling sites ranged from 0 to 47.06% and that among the 4 age groups ranged from 18.50 to 43.81%. SSU rRNA sequence analysis and RFLP analysis revealed the presence of 4 Cryptosporidium species, namely, C. bovis (44.37%), C. andersoni (35.10%), C. ryanae (21.85%), and C. parvum (11.92%), along with a mixed infection involving two or three Cryptosporidium species. Cryptosporidium bovis or C. andersoni was the most common cause of infection in the four age groups. The subtype of C. parvum was successfully identified as IIdA via gp60 analysis; all isolates were identified as the subtype IIdA19G1. CONCLUSIONS: To the best of our knowledge, this is the first report of dairy cattle infected with four Cryptosporidium species in Inner Mongolia, China, along with a mixed infection involving two or three Cryptosporidium species, with C. bovis and C. andersoni as the dominant species. Moreover, this is the first study to identify C. parvum subtype IIdA19G1 in cattle in Inner Mongolia. Our study findings provide detailed information on molecular epidemiological investigation of bovine cryptosporidiosis in Inner Mongolia, suggesting that dairy cattle in this region are at risk of transmitting cryptosporidiosis to humans.

SCASP: A Simple and Robust SDS-Aided Sample Preparation Method for Proteomic Research.

SDS is widely used in sample preparation for proteomic research. However, SDS is incompatible with LC and electrospray ionization. SDS depletion is therefore required ahead of LC-MS analysis. Most of current SDS removal strategies are time consuming, laborious, and have low reproducibility. Here, we describe a method, SDS-cyclodextrin (CD)-assisted sample preparation, by which CD can bind to SDS and form CD-SDS complexes in solutions, allowing for direct tryptic digestion. We demonstrate that SDS-CD-assisted sample preparation is a simple, fast, and robust SDS-based sample preparation method for proteomics application.

Prediction of osteoporosis using radiomics analysis derived from single source dual energy CT.

BACKGROUND: With the aging population of society, the incidence rate of osteoporosis is increasing year by year. Early diagnosis of osteoporosis plays a significant role in the progress of disease prevention. As newly developed technology, computed tomography (CT) radiomics could discover radiomic features difficult to recognize visually, providing convenient, comprehensive and accurate osteoporosis diagnosis. This study aimed to develop and validate a clinical-radiomics model based on the monochromatic imaging of single source dual-energy CT for osteoporosis prediction. METHODS: One hundred sixty-four participants who underwent both single source dual-energy CT and quantitative computed tomography (QCT) lumbar-spine examination were enrolled in a study cohort including training datasets (n = 114 [30 osteoporosis and 84 non-osteoporosis]) and validation datasets (n = 50 [12 osteoporosis and 38 non-osteoporosis]). One hundred seven radiomics features were extracted from 70-keV monochromatic CT images. With QCT as the reference standard, a radiomics signature was built by using least absolute shrinkage and selection operator (LASSO) regression on the basis of reproducible features. A clinical-radiomics model was constructed by incorporating the radiomics signature and a significant clinical predictor (age) using multivariate logistic regression analysis. Model performance was assessed by its calibration, discrimination and clinical usefulness. RESULTS: The radiomics signature comprised 14 selected features and showed good calibration and discrimination in both training and validation cohorts. The clinical-radiomics model, which incorporated the radiomics signature and a significant clinical predictor (age), also showed good discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.938 (95% confidence interval, 0.903-0.952) in the training cohort and an AUC of 0.988 (95% confidence interval, 0.967-0.998) in the validation cohort, and good calibration. The clinical-radiomics model stratified participants into groups with osteoporosis and non-osteoporosis with an accuracy of 94.0% in the validation cohort. Decision curve analysis (DCA) demonstrated that the radiomics signature and the clinical-radiomics model were clinically useful. CONCLUSIONS: The clinical-radiomics model incorporating the radiomics signature and a clinical parameter had a good ability to predict osteoporosis based on dual-energy CT monoenergetic imaging.

Transcriptome analysis reveals molecular regulation mechanism of Tibet sheep tolerance to high altitude oxygen environment.

As one of the most important livestock breeds on the Qinghai-Tibet Plateau, Tibetan sheep are of great importance to the local economy, agriculture and culture. Its adaptive mechanism in low temperature and low oxygen at highland altitudes has not been reported. In this study, transcriptome sequencing was used to analyze the heart, liver, spleen, lung, kidney, and muscle tissue of sheep at low and highland altitudes. LOC101112291, SELENOW, COL3A1, GPX1, TMSB4X and HSF4 were selected as candidate genes for adapting to plateau characteristics in Tibet Sheep. Besides, glutathione metabolism, arachidonic acid metabolism, nucleotide excision repair, regulation of actin cytoskeleton, protein digestion and absorption, thyroid hormone synthesis, relaxation signaling pathways may play important roles in the adaptation to plateau hypoxia, and cold tolerance. Structural analysis also showed that sequencing genes related to the adaptation mechanism of Tibet sheep to highland altitude. This study will lay a certain foundation for Tibet sheep research.

Tibet sheep are an ancient species in the Qinghai Tibet Plateau. After a long period of domestication. Tibet sheep adapt to the hypoxic environment of the plateau in terms of physiology and morphology. At the same time, Tibet sheep is also one of the major sources of material for herdsmen in tibetan. In this study, six different tissue samples (heart, liver, spleen, lung, kidney, and muscle) of Tibet sheep were analyzed to reveal the underlying mechanisms of different tissues respond to hypothermia condition. The results showed that six key genes and eight important signaling pathways involved in regulating the adaptation of Tibet sheep to the plateau. In addition, there were more alternative splicing (AS) events and single nucleotide polymorphism (SNP) sites in highland altitude Tibet sheep than in lowland altitude sheep, which was also a concern in the highland altitude adaptability of Tibet sheep.

Prevalence and molecular characterization of Cryptosporidium spp. in dairy and beef cattle in Shanxi, China.

Cryptosporidium spp. are key gastrointestinal protists in humans and animals worldwide. Infected cattle are considered the main source of cryptosporidiosis outbreaks in humans. However, little is known about the genetic makeup of Cryptosporidium populations in Shanxi province, China. We analyzed 858 fecal samples collected from farms in Shanxi. The presence of Cryptosporidium spp. was determined via polymerase chain reaction and subsequent sequence analysis of the small subunit rRNA gene as well as restriction fragment length polymorphism analysis. Cryptosporidium parvum was subtyped following sequence analysis of the 60 kDa glycoprotein gene (gp60). The overall prevalence of Cryptosporidium in cattle was 11.19%, with a prevalence of 13.30% and 8.67% in Lingqiu and Yingxian, respectively. The overall prevalence of Cryptosporidium in dairy and beef cattle was 10.78% and 11.50%, respectively. Cryptosporidium infection was detected across all analyzed age groups. The overall prevalence of Cryptosporidium in diarrhea and nondiarrhea samples was 18.24% and 9.72%, respectively, whereas that in intensively farmed and free-range cattle was 17.40% and 3.41%, respectively. We identified five Cryptosporidium species, with C. andersoni being the dominant species. Further, two cases of mixed infections of Cryptosporidium species were detected. All identified C. parvum isolates belonged to the subtype IIdA17G1.

Mitochondrial iron overload mediated by cooperative transfer of plasma membrane ATP5B and TFR2 to mitochondria triggers hepatic insulin resistance under PFOS exposure.

In general populations, insulin resistance (IR) is related to perfluorooctane sulfonate (PFOS), a persistent organic pollutant. However, the underlying mechanism remains unclear. In this study, PFOS induced mitochondrial iron accumulation in the liver of mice and human hepatocytes L-O2. In the PFOS-treated L-O2 cells, mitochondrial iron overload preceded the occurrence of IR, and pharmacological inhibition of mitochondrial iron relieved PFOS-caused IR. Both transferrin receptor 2 (TFR2) and ATP synthase ß subunit (ATP5B) were redistributed from the plasma membrane to mitochondria with PFOS treatment. Inhibiting the translocation of TFR2 to mitochondria reversed PFOS-induced mitochondrial iron overload and IR. In the PFOS-treated cells, ATP5B interacted with TFR2. Stabilizing ATP5B on the plasma membrane or knockdown of ATP5B disturbed the translocation of TFR2. PFOS inhibited the activity of plasma-membrane ATP synthase (ectopic ATP synthase, e-ATPS), and activating e-ATPS prevented the translocation of ATP5B and TFR2. Consistently, PFOS induced ATP5B/TFR2 interaction and redistribution of ATP5B and TFR2 to mitochondria in the liver of mice. Thus, our results indicated that mitochondrial iron overload induced by collaborative translocation of ATP5B and TFR2 was an up-stream and initiating event for PFOS-related hepatic IR, providing novel understandings of the biological function of e-ATPS, the regulatory mechanism for mitochondrial iron and the mechanism underlying PFOS toxicity.