Contamination of dairy products with tris(2,4-di-tert-butylphenyl) phosphite and implications for human exposure.

Tris(2,4-di-tert-butylphenyl) phosphite (AO168), an organophosphite antioxidant, can be oxidized to tris(2,4-di-tert-butylphenyl) phosphate (AO168 = O) during the production, processing, and application of plastics. AO168 = O can be further transformed to bis(2,4-di-tert-butylphenyl) phosphate and 2,4-di-tert-butylphenol. Here, we discovered the contamination of AO168 and its transformation products in dairy products for the first time. More samples contained AO168 (mean concentration: 8.78 ng/g wet weight [ww]), bis(2,4-di-tert-butylphenyl) phosphate (mean:11.1 ng/g ww) and 2,4-di-tert-butylphenol (mean: 46.8 ng/g ww) than AO168 = O (mean: 40.2 ng/g ww). The concentrations of AO168 and its transformation products were significantly correlated, and differed with the packaging material and storage conditions of the product. Estimated daily intakes (EDIs) of AO168 and its transformation products were calculated. Although the overall dietary risks were below one, transformation products accounted for 96.7% of the total hazard quotients. The high-exposure EDIs of total AO168 were above the threshold of toxicological concern (300 ng/kg bw/day), and deserve continual monitoring.

PNO1 promotes the progression of osteosarcoma via TGF-ß and YAP/TAZ pathway.

This study aimed to explore the potential role and mechanisms of the partner of NOB1 homolog (PNO1) in osteosarcoma. The expression of PNO1 in tumor and adjacent tissue samples was examined using western blotting. Lentiviral transfection was used to establish sh-Ctrl and sh-PNO1 osteosarcoma cell lines. MTT assay, Celigo cell cytometer count, and cell colony formation assay were used to investigate the proliferation of osteosarcoma cells in vitro, whereas xenotransplantation assay was performed for in vivo experiments. Wound-healing and Transwell assays were chosen to verify the migration and invasion of osteosarcoma cells. Flow cytometry assay and caspase-3/7 activity analysis were adopted for the analysis of cell apoptosis and cell cycle. Finally, transcriptome sequencing and bioinformatics analysis were adopted to explore the acting mechanisms. The expression of PNO1 was higher in osteosarcoma tissues than that in adjacent tissues. Down-regulation of PNO1 inhibited the proliferation, migration, and invasion, and induced cell apoptosis and cell cycle arrest of osteosarcoma cells. Furthermore, according to transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analysis, we found that PNO1 might affect the progression of osteosarcoma via TGF-ß and YAP/TAZ signaling pathways. PNO1 could be a potential target for osteosarcoma treatment.

Inhibition of neutrophil extracellular trap formation ameliorates neuroinflammation and neuronal apoptosis via STING-dependent IRE1α/ASK1/JNK signaling pathway in mice with traumatic brain injury.

BACKGROUND: Neuroinflammation is one of the most important pathogeneses in secondary brain injury after traumatic brain injury (TBI). Neutrophil extracellular traps (NETs) forming neutrophils were found throughout the brain tissue of TBI patients and elevated plasma NET biomarkers correlated with worse outcomes. However, the biological function and underlying mechanisms of NETs in TBI-induced neural damage are not yet fully understood. Here, we used Cl-amidine, a selective inhibitor of NETs to investigate the role of NETs in neural damage after TBI. METHODS: Controlled cortical impact model was performed to establish TBI. Cl-amidine, 2'3'-cGAMP (an activator of stimulating Interferon genes (STING)), C-176 (a selective STING inhibitor), and Kira6 [a selectively phosphorylated inositol-requiring enzyme-1 alpha [IRE1α] inhibitor] were administrated to explore the mechanism by which NETs promote neuroinflammation and neuronal apoptosis after TBI. Peptidyl arginine deiminase 4 (PAD4), an essential enzyme for neutrophil extracellular trap formation, is overexpressed with adenoviruses in the cortex of mice 1 day before TBI. The short-term neurobehavior tests, magnetic resonance imaging (MRI), laser speckle contrast imaging (LSCI), Evans blue extravasation assay, Fluoro-Jade C (FJC), TUNEL, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative-PCR were performed in this study. RESULTS: Neutrophils form NETs presenting in the circulation and brain at 3 days after TBI. NETs inhibitor Cl-amidine treatment improved short-term neurological functions, reduced cerebral lesion volume, reduced brain edema, and restored cerebral blood flow (CBF) after TBI. In addition, Cl-amidine exerted neuroprotective effects by attenuating BBB disruption, inhibiting immune cell infiltration, and alleviating neuronal death after TBI. Moreover, Cl-amidine treatment inhibited microglia/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization at 3 days after TBI. Mechanistically, STING ligand 2'3'-cGAMP abolished the neuroprotection of Cl-amidine via IRE1α/ASK1/JNK signaling pathway after TBI. Importantly, overexpression of PAD4 promotes neuroinflammation and neuronal death via the IRE1α/ASK1/JNK signaling pathway after TBI. However, STING inhibitor C-176 or IRE1α inhibitor Kira6 effectively abolished the neurodestructive effects of PAD4 overexpression after TBI. CONCLUSION: Altogether, we are the first to demonstrate that NETs inhibition with Cl-amidine ameliorated neuroinflammation, neuronal apoptosis, and neurological deficits via STING-dependent IRE1α/ASK1/JNK signaling pathway after TBI. Thus, Cl-amidine treatment may provide a promising therapeutic approach for the early management of TBI.

Activatable Graphene Quantum-Dot-Based Nanotransformers for Long-Period Tumor Imaging and Repeated Photodynamic Therapy.

Photodynamic therapy (PDT) is considered as an emerging therapeutic modality against cancer with high spatiotemporal selectivity because the utilized photosensitizers (PSs) are only active and toxic upon light irradiation. To maximize its effectiveness, PDT is usually applied repetitively for ablating various tumors. However, the total overdose of PSs from repeated administrations causes severe side effects. Herein, acidity-activated graphene quantum dots-based nanotransformers (GQD NT) are developed as PS vehicles for long-period tumor imaging and repeated PDT. Under the guidance of Arg-Gly-Asp peptide, GQD NT targets to tumor tissues actively, and then loosens and enlarges in tumor acidity, thus promising long tumor retention. Afterwards, GQD NT transforms into small pieces for better penetration in tumor. Upon laser irradiation, GQD NT generates mild hyperthermia that enhances cell membrane permeability and further promotes the PSs uptake. Most intriguingly, the as-prepared GQD NT not only "turns-on" fluorescence/magnetic resonance signals, but also achieves efficient repeated PDT. Notably, the total PSs dose is reduced to 3.5 µmol kg-1 , which is 10-30 times lower than that of other reported works. Overall, this study exploits a smart vehicle to enhance accumulation, retention, and release of PSs in tumors through programmed deformation, thus overcoming the overdose obstacle in repeated PDT.

Effect of blood flow-restricted resistance training on myocardial fibrosis in early spontaneously hypertensive rats.

Objective: The purpose of this study was to explore the effect of blood flow-restricted resistance training on myocardial fibrosis in early spontaneously hypertensive rats (SHRs). Methods: Four-week-old male Wistar-Kyoto rats and SHRs were randomly divided into the following groups: normal group (WKY), SHR control (SHR-SED) group, high-intensity resistance training (HIRT) group, low- and medium-intensity resistance training (LMIRT) group, and blood flow-restricted low- and medium-resistance training (BFRT) group. Body weight, hemodynamics, cardiac function, myocardial morphology and fibrosis, and the expression levels of transforming growth factor-beta1-Smad (TGFß-1-Smad) pathway-related proteins in the myocardium were assessed. Results: (1) BFRT lowered blood pressure significantly, decreased left ventricular wall thickness, and improved cardiac function. At the same time, BFRT was superior to traditional resistance training in lowering diastolic blood pressure, and was superior to HIRT in improving left ventricular compliance, reducing heart rate, and reducing left ventricular posterior wall and left ventricular mass (P < 0.05). (2) BFRT decreased collagen I and collagen fiber area in the myocardium, increased the collagen III area, and decreased the collagen I/III ratio (P < 0.05). BFRT produced a better proportion of myocardial collagen fibers than did traditional resistance training (P < 0.05). (3) In the myocardium of the BFRT group compared to the traditional resistance training group, the expression of TGFß-1, Smad2/3/4, p-Smad2/3, CTGF, and TIMP1 was significantly downregulated, MMP2 and TIMP2 were significantly upregulated, the MMP/TIMP ratio significantly increased, and TGFß-1 expression significantly decreased (P < 0.05). Conclusion: BFRT inhibited the TGFß-1-Smad pathway in the myocardium, downregulated the expression of CTGF, and regulated the balance between MMPs and TIMPs, thereby reducing myocardial fibrosis in SHR, and improving cardiac morphology and function. BFRT also lowered blood pressure, and achieved an effect of early prevention and treatment of hypertension. At the same time, BFRT was superior to traditional resistance training in reducing diastolic blood pressure and adjusting the proportion of myocardial collagen fibers.

Percutaneous nephroscopy combined with the laser used for right kidney bullet extraction: A case report.

RATIONALE: Wounds caused by firearms are intractable problems in treating war traumas and clinical management. Conventional open surgery inflicts large injury and leads to slow recovery. At the same time, most patients suffer from compound injuries with the critical condition and poor operation tolerance. Thus, it is crucial to probe into the minimally invasive surgical removal of residual kidney bullets. PATIENT CONCERNS: We report a case where a bullet remained in the right renal parenchyma on the patient, with penetrating injury in his liver. DIAGNOSIS: Obviously the patient has suffered gunshot wound with a bullet stuck in his kidney, while his liver function was impacted. INTERVENTIONS: Six months after the injury, we performed the minimally-invasive procedures on the patient with percutaneous nephroscope technology and laser technology under the guidance of ultrasound localization. The bullet and ammunition granulation and scar surrounding tissue were fully removed. Intraoperative bleeding was little, while the incision was small. The patient could leave the bed and walk on the 1st postoperative day. The drainage tube was removed on the 3rd postoperative day, after which the patient was discharged on the 4th postoperative day. OUTCOMES: The patient recovered well after surgery and was followed up for 5 years. The latest examination of his liver and kidney function was as follows: alanine aminotransferase 61IU/L, aspartate aminotransferase 33 IU/L, albumin/globulin 46.6/26.0, total bilirubin 19.1µmol/L, direct bilirubin 4.9µmol/L, indirect bilirubin 14.2µmol/L, alkaline phosphatase 111 IU/L, creatinine 57µmol/L, urea 5.16mmol/L, cystatin 0.73mg/L. The plain computed tomography scan showed a few calcifications in the liver and a patchy low-density shadow in the right kidney. It was proved that the liver and kidney function of the patient recovered well, and his living qualify has come back to the track, with no postoperative complications. LESSONS: Innovative integration of percutaneous nephroscopy technology and laser was used to remove kidney foreign bodies and developed the optimal surgical plan, small trauma, fast recovery, and the treatment of kidney foreign bodies was newly explored.

Cytomegalovirus-specific neutralizing antibodies effectively prevent uncontrolled infection after allogeneic hematopoietic stem cell transplantation.

Cytomegalovirus (CMV) infection remains one of the most frequent and life-threatening infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Herein, we comprehensively compared the immune cells of patients with uncontrolled and controlled CMV infection post-allo-HSCT and found that B-cells were extraordinarily insufficient because of impaired B-cells reconstitution in the uncontrolled infection group. Furthermore, in the controlled infection group, reconstructed B-cells showed signatures of mature B-cells, high expression of CXCR4 and IFITM1, and enrichment of CMV-associated B-cell receptors, which were lacking in the uncontrolled infection group. Consistently, sera from the uncontrolled infection group failed to inhibit CMV infection via neutralizing virus in vitro because of its lower content of anti-CMV-specific immunoglobulin G (IgG) than the controlled infection group. Overall, these results highlighted the contribution of B cells and anti-CMV-specific neutralizing IgGs to the restraint of CMV infection post-allo-HSCT, suggesting their potential as a supplementary treatment to improve outcomes.

New dual-function in situ bone repair scaffolds promote osteogenesis and reduce infection.

BACKGROUND: The treatment of infectious bone defects is a difficult problem to be solved in the clinic. In situ bone defect repair scaffolds with anti-infection and osteogenic abilities can effectively deal with infectious bone defects. In this study, an in situ polycaprolactone (PCL) scaffold containing ampicillin (Amp) and Mg microspheres was prepared by 3D printing technology. RESULTS: Mg and Amp were evenly distributed in PCL scaffolds and could be released slowly to the surrounding defect sites with the degradation of scaffolds. In vitro experiments demonstrated that the PCL scaffold containing Mg and Amp (PCL@Mg/Amp) demonstrated good cell adhesion and proliferation. The osteogenic genes collagen I (COL-I) and Runx2 were upregulated in cells grown on the PCL@Mg/Amp scaffold. The PCL@Mg/Amp scaffold also demonstrated excellent antibacterial ability against E. coli and S. aureus. In vivo experiments showed that the PCL@Mg/Amp scaffold had the strongest ability to promote tibial defect repair in rats compared with the other groups of scaffolds. CONCLUSIONS: This kind of dual-function in situ bone repair scaffold with anti-infection and osteogenic abilities has good application prospects in the field of treating infectious bone defects.

Correction: Rapid and sensitive leukemia-derived exosome quantification via nicking endonuclease-assisted target recycling.

Correction for 'Rapid and sensitive leukemia-derived exosome quantification via nicking endonuclease-assisted target recycling' by Mengyang Zhou et al., Anal. Methods, 2021, 13, 4001-4007, https://doi.org/10.1039/D1AY00854D.

In-situ formed nanoscale Fe0 for fenton-like oxidation of thermosetting unsaturated polyester resin composites: Nondestructively recycle carbon fiber.

Thermosetting unsaturated polyester resin (UPR) composites were found widespread industrial applications. However, the numerous stable carbon-carbon bonds in cross-linked networks made them intractable for degradation, causing the large-scale composite wastes. Here a nanoscale Fe0 catalyst in-situ forming strategy was exploited to nondestructively recycle carbon fiber (CF) from UPR composites via Fenton-like reaction. The nano-Fe0 catalyst employed in this strategy activated H2O2 for removing UPR, featuring mild conditions and efficient degradation ability. Aiming at facile growth of the catalyst, a porous UPR was achieved by the hydrolysis of alkalic system. The nanoscale Fe0 catalyst was subsequently formed in-situ on the surface of hydrolyzed resin by borohydride reduction. Benefiting from fast mass transfer, the in-situ grown nano-Fe0 showed more efficient degradation ability than added nano-Fe0 or Fe2+ catalyst during Fenton-like reaction. The experiments indicated that hydrolyzed resin could be degraded more than 90% within 80 min, 80 °C. GC-MS, FT-IR analysis and Density functional theory (DFT) calculation were conducted to explained the fracture processes of carbon skeleton in hydrolyzed resin. Especially, a remarkable recovery process of CF from composites was observed, with a 100 percent elimination of resin. The recycled CF cloth exhibited a 99% strength retention and maintained the textile structure, microtopography, chemical structure, resulting in the nondestructive reclaim of CF. This in-situ formed nanoscale Fe0 catalytic degradation strategy may provide a promising practical application for nondestructively recycle CF from UPR composites.

Highly efficient thermoelectric air conditioner with kilowatt capacity realized by ground source heat-exchanging system.

The enormous need for refrigeration of modern human life has inevitably aggravated the environmental crisis worldwide. To date, there are very few refrigeration technologies available beholding both harmless refrigerants and high efficiency. Here, we proposed a geothermal-thermoelectric air conditioning system (GeoTEAC) with refrigerant-free and high energy efficiency through synergistically combining the merits of thermoelectric effect and ground source heat exchanging system. The system showed competitive cooling and heating COPs of 5.83 and 2.92, respectively, with kilowatt capacity, which are 3-4 times higher than that of previously reported thermoelectric air-conditioning setups. For a conceptual scenario, we demonstrated the lowest TEWI values for the GeoTEAC system among different air-conditioning types. Our work provides sustainable and climate-friendly solutions to realize worldwide emission peaks and carbon neutralization.

γ-Ray-driven degradation of robust epoxy thermosets.

The γ ray is a promising candidate for thermoset material degradation owing to its high energy, strong penetrability, low carbon emission and economy. However, the development of irradiation degradation technology is limited by irradiation cross-linking and irradiation degradation simultaneously, and a controllable degradation remains a considerable challenge. Herein, we exploit stable conjugated linkages, phenyl imine conjugated N-N bonds, for the γ-ray-induced controllable cleavage of polymer chains. Using this distinctive conjugated structure, we design γ-ray-responsive epoxy networks that can be readily degraded at a dose of 40 kGy at room temperature and show mechanical properties, thermal properties and chemical resistance comparable to commodity epoxy resins. Additionally, the incorporation of a radical scavenger can reduce the uncontrolled recombination of degradation segments, which further accelerates the degradation of the epoxy thermosets.

The effects of fructose diphosphate on routine coagulation tests in vitro.

To evaluate the effects of fructose diphosphate (FDP) on routine coagulation tests in vitro, we added FDP into the mixed normal plasma to obtain the final concentration of 0, 1, 2, 3, 4, 5, 6, 10, 15, 20, 25, 30 and 35 mg/mL of drug. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (FBG) and thrombin time (TT) of samples were analyzed with blood coagulation analyzers from four different manufacturers(Sysmex, Stago, SEKISUI and Werfen) and their corresponding reagents, respectively. Before the experiment, we also observed whether there were significant differences in coagulation test results of different lots of reagents produced by each manufacturer. At the same time as the four routine clotting tests, the Sysmex blood coagulation analyzer and its proprietary analysis software were used to detect the change of maximum platelet aggregation rate in platelet-rich plasma after adding FDP (0, 1, 2, 3, 4, 5 and 6 mg/mL). The results of PT, aPTT and TT showed a FDP (0-35 mg/mL) concentration-dependent increase and a FBG concentration-dependent decrease. The degree of change (increase or decrease) varied depending on the assay system, with PT and aPTT being more affected by the Sysmex blood coagulation testing instrument reagent system and less affected by CEKISUI, TT less affected by CEKISUI and more affected by Stago, and FBG less affected by Stago and more affected by Sysmex. The results of PT, aPTT and TT were statistically positively correlated with their FDP concentrations, while FBG was negatively correlated. The correlation coefficients between FDP and the coagulation testing systems of Sysmex, Stago, Werfen and SEKISUI were 0.975, 0.988, 0.967, 0.986 for PT, and 0.993, 0.989, 0.990 and 0.962 for aPTT, 0.994, 0.960, 0.977 and 0.982 for TT, - 0.990, - 0.983, - 0.989 and - 0.954 for FBG, respectively. Different concentrations of FDP (0, 1, 2, 3, 4, 5 and 6 mg/mL) had different effects on the maximum aggregation rate of platelet induced by the agonists of adenosine diphosphate (ADP, 5 µmol/L), arachidonic acid (Ara, 1 mmol/L), collagen (Col, 2.5 µg/mL) and epinephrine (Epi,10 µmol/L), but the overall downward trend was consistent, that is, with the increase of FDP concentration, the platelet aggregation rate decreased significantly. Our experimental study demonstrated a possible effect of FDP on the assays of coagulation and Platelet aggregation, which may arise because the drug interferes with the coagulation and platelet aggregation detection system, or it may affect our in vivo coagulation system and Platelet aggregation function, the real mechanism of which remains to be further verified and studied.

Ultrasensitive molecular building block for biothiol NMR detection at picomolar concentrations.

Magnetic resonance imaging (MRI) provides structural and functional information, but it did not probe chemistry. Chemical information could help improve specificity of detection. Herein, we introduce a general method based on a modular design to construct a molecular building block Xe probe to help image intracellular biothiols (glutathione (GSH), cysteine (Cys) and homocysteine (Hcy)), the abnormal content of which is related to various diseases. This molecular building block possesses a high signal-to-noise ratio and no background signal effects. Its detection threshold was 100 pM, which enabled detection of intracellular biothiols in live cells. The construction strategy can be easily extended to the detection of any other biomolecule or biomarker. This modular design strategy promotes efficiency of development of low-cost multifunctional probes that can be combined with other readout parameters, such as optical readouts, to complement 129Xe MRI to usher in new capabilities for molecular imaging.

Clinical Characteristics and Inflammatory Immune Responses in COVID-19 Patients With Hypertension: A Retrospective Study.

Coronavirus disease (COVID-19) patients with cardiovascular and metabolic disorders have been found to have a high risk of developing severe conditions with high mortality, further affecting the prognosis of COVID-19. However, the effect of hypertension and angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blocker (ARB) agents on the clinical characteristics and inflammatory immune responses in COVID-19 patients is still undefined. In this study, 90 COVID-19 patients were divided into hypertension and nonhypertension groups. The hypertension group was divided into well-controlled and poorly controlled subgroups based on blood pressure levels; moreover, hypertensive patients were also divided into ACEI/ARB and non-ACEI/ARB subgroups according to the administration of ACEI/ARB antihypertensive agents. The clinical characteristics of and inflammatory immune biomarker levels in the different groups of COVID-19 patients were compared, and the association between the combined effect of hypertension with ACEI/ARB antihypertensive agents and the severity of COVID-19 was examined. The results showed that the levels of aminotransferase (AST) and hs-cTnI were higher in the hypertension group compared with the nonhypertension group. The long-term use of ACEI/ARB agents in patients had statistically significantly lower AST, low-density lipoprotein cholesterol (LDL-C), and oxygen uptake and lower white cell count, neutrophil count, and levels of CD4, CD8, CRP, and PCT but without statistical significance. In addition, compared with COVID-19 patients without hypertension, hypertensive patients without the use of ACEI/ARB had a higher risk of developing severity of COVID-19 (for poorly controlled patients: OR = 3.97, 95% CI = 1.03-15.30; for well-controlled patients: OR = 6.48, 95% CI = 1.77-23.81). Hypertension could cause organ damage in COVID-19 patients, but the long-term use of ACEI/ARB agents may be beneficial to alleviate this injury.

Rapid and sensitive leukemia-derived exosome quantification via nicking endonuclease-assisted target recycling.

Exosomes as fluid biomarkers hold great promise for noninvasive cancer diagnosis. However, a method for the rapid and convenient detection of exosomes is still a challenge because current analysis processes involve multiple steps and yield low sensitivity. Here, we developed a wash-free fluorescent biosensor for the rapid and sensitive quantification of exosomes by combining aptamer and nicking endonuclease (Nb·BbvCI). In this system, an aptamer-trigger complex was used as the recognition element; the trigger probe could be released, and it hybridized with gold nanoparticles (GNPs)-DNA-FAM conjugates, thereby resulting in Nb·BbvCI-assisted target recycling. As a result, our method allowed the quantification of exosomes with lower analysis time by using a cocktail containing an aptamer-trigger complex, Nb·BbvCI, and GNPs-DNA-FAM. A high sensitivity with a limit of detection (LOD) of 1.0 × 104 particles per µL could be achieved. Besides, this biosensor exhibited potential application for the quantification of exosomes in human plasma, facilitating the development of exosome-based noninvasive cancer diagnosis.

Diagnosing scrub typhus without eschar: a case report using metagenomic next-generation sequencing (mNGS).

Scrub typhus is a disease caused by the bacteria, Orientia tsutsugamushi, which is spread to people through the bites of infected larval mites. Symptoms include eschar at the place of infection, as well as many flu-like symptoms, e.g., fever, headache, chills and skin rash. As eschar is the most typical symptom of scrub typhus, it is often used to diagnose the disease, but if a patient does not display an obvious eschar lesion, diagnosing the disease can prove to be difficult. To help improve the diagnoses of scrub typhus, metagenomic next-generation sequencing (mNGS) has been used as a new approach to identifying pathogens. Here, we report a 51-year-old patient who had unexplained fever for a week and was admitted to hospital with no obvious eschar on her body. Smears and cultures of blood and sputum samples were first performed, but all returned a negative result for scrub typhus. We then conducted a mNGS analysis of blood and sputum samples and were able to identify the pathogenic microbe. Subsequently, a total of 377 reads, as well as 12 unique reads of Orientia tsutsugamushi were detected in the patient's blood and sputum. Quantitative polymerase chain reaction (qPCR) results of blood samples further confirmed our mNGS detection, suggesting that the patient did indeed have scrub typhus. From these results, we determined that mNGS as a diagnostic tool provides a better method of identifying clinical febrile pathogens with atypical characteristics.

FOXP3 Inhibits the Metastasis of Breast Cancer by Downregulating the Expression of MTA1.

BACKGROUND: FOXP3, as a tumour suppressor gene, has a vital function in inhibiting the metastasis of breast cancer cells, but the mechanisms by which it inhibits metastasis have not been fully elucidated. This study intended to explore a new mechanism by which FOXP3 inhibits breast cancer metastasis. METHODS: Bioinformatic analysis was performed to identify potential downstream molecules of FOXP3. The function of FOXP3 in inhibiting MTA1 expression at the mRNA and protein levels was verified by real-time PCR and Western blot analysis. The interaction between FOXP3 and the MTA1 promoter was verified by transcriptomic experiments. In vitro and in vivo experiments were used to determine whether the regulation of MTA1 by FOXP3 affected the invasion and migration of breast cancer cells. Immunohistochemistry was adopted to explore the correlation between the expression levels of FOXP3 and MTA1 in breast cancer samples. RESULTS: Bioinformatics-based sequencing suggested that MTA1 is a potential downstream molecule of FOXP3. FOXP3 downregulated the expression of MTA1 in breast cancer cells by directly inhibiting MTA1 promoter activity. Importantly, FOXP3's regulation of MTA1 affected the ability of breast cancer cells to invade and metastasize in vitro and in vivo. Moreover, analysis of clinical specimens showed a significant negative correlation between the expression levels of FOXP3 and MTA1 in breast cancer. CONCLUSION: We systematically explored a new mechanism by which FOXP3 inhibits breast cancer metastasis via the FOXP3-MTA1 pathway.

Pulling-Force Spinning Top for Serum Separation Combined with Paper-Based Microfluidic Devices in COVID-19 ELISA Diagnosis.

The spread of Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), resulting in a global pandemic with around four million deaths. Although there are a variety of nucleic acid-based tests for detecting SARS-CoV-2, these methods have a relatively high cost and require expensive supporting equipment. To overcome these limitations and improve the efficiency of SARS-CoV-2 diagnosis, we developed a microfluidic platform that collected serum by a pulling-force spinning top and paper-based microfluidic enzyme-linked immunosorbent assay (ELISA) for quantitative IgA/IgM/IgG measurements in an instrument-free way. We further validated the paper-based microfluidic ELISA analysis of SARS-CoV-2 receptor-binding domain (RBD)-specific IgA/IgM/IgG antibodies from human blood samples as a good measurement with higher sensitivity compared with traditional IgM/IgG detection (99.7% vs 95.6%) for early illness onset patients. In conclusion, we provide an alternative solution for the diagnosis of SARS-CoV-2 in a portable manner by this smart integration of pulling-force spinning top and paper-based microfluidic immunoassay.