MiR-30c suppresses the proliferation, metastasis and polarity reversal of tumor cell clusters by targeting MTDH in invasive micropapillary carcinoma of the breast.

Purpose: Invasive micropapillary carcinoma (IMPC) of the breast has a high propensity for lymphovascular invasion and axillary lymph node metastasis and displays an 'inside-out' growth pattern, but the molecular mechanism of invasion, metastasis and cell polarity reversal in IMPC is unclear. Methods: and Patients: Cell growth curves, tumor sphere formation assays, transwell assays, mouse xenograft model and immunofluorescence were evaluated to investigate the effects of miR-30c and MTDH. Dual luciferase reporter assays was performed to confirm that the MTDH (metadherin) 3'UTR bound to miR-30c. MiRNA in situ hybridization (ISH) and immunohistochemistry (IHC) were carried out on IMPC patient tissues for miR-30c and MTDH expression, respectively. Results: We found miR-30c as a tumor suppressor gene in cell proliferation, metastasis and polarity reversal of IMPC. Overexpression of miR-30c inhibited cell growth and metastasis in vitro and in vivo. MiR-30c could directly target the MTDH 3'UTR. MiR-30c overexpression inhibited breast cancer cell proliferation, invasion and metastasis by targeting MTDH. Moreover, miR-30c/MTDH axis could also regulate cell polarity reversal of IMPC. By ISH and IHC analyses, miR-30c and MTDH were significantly correlated with tumor size, lymph nodule status and tumor grade, the 'inside-out' growth pattern, overall survival (OS) and disease-free survival (DFS) in IMPC patients. Conclusions: Overall, miR-30c/MTDH axis was responsible for tumor proliferation, metastasis and polarity reversal. It may provide promising therapeutic targets and prognostic biomarkers for patients with IMPC.

Fasting Blood Glucose-Based Novel Predictors in Detecting Metastases and Predicting Prognosis for Patients with PNENs.

OBJECTIVE: To explore three novel fasting blood glucose (FBG)-based novel indicators, including the FBG-to-albumin ratio (FAR), FBG-to-lymphocytes ratio (FLR), and FBG-to-hemoglobin ratio (FHR), in predicting prognosis and detecting metastasis for patients with pancreatic neuroendocrine neoplasms (pNENs) after resection. MATERIALS AND METHODS: A total of 178 pNENs patients who underwent surgical resection were included in this study. Receiver operating characteristic (ROC) curves were used to evaluate the diagnosis values of FAR, FLR, and FHR, and the cutoff values were obtained for further analyses. Univariate and multivariate analyses were conducted to determine the independent predictors. The Kaplan-Meier method was used to evaluate the progression-free survival (PFS) and overall survival (OS) of the pNENs patients. RESULTS: The optimal cutoff values of FAR, FLR, and FHR were 0.17, 2.85, and 0.028, respectively. As for PFS, the area under the curve (AUC) was 0.693 for FAR, 0.690 for FLR, and 0.661 for FHR, respectively. The AUC was 0.770, 0.692, and 0.715 accordingly for OS. The groups with lower FAR, FLR, and FHR were significantly associated with prolonged PFS and OS (p < 0.05). In patients with metastasis, the lower FAR group was correlated with significantly longer PFS and OS (p = 0.022 and 0.002, respectively). The FLR was an independent predictor of PFS in pNENs patients, and the FAR was a predictor of OS. FAR was an independent indicator of PFS in patients with metastasis. CONCLUSIONS: Preoperative FAR, FLR, and FHR are effective in predicting the prognosis of pNEN patients and detecting the synchronous metastases.

Epoxidized Soybean Oil Toughened Poly(lactic acid)/Lignin-g-Poly(lauryl methacrylate) Bio-Composite Films with Potential Food Packaging Application.

The application of lignin as a filler for poly (lactic acid) (PLA) is limited by their poor interfacial adhesion. To address this challenge, lignin-graft-poly(lauryl methacrylate) (LG-g-PLMA) was first blended with poly (lactic acid), and then epoxidized soybean oil (ESO) was also added to prepare PLA/LG-g-PLMA/ESO composite, which was subsequently hot pressed to prepare the composite films. The effect of ESO as a plasticizer on the thermal, mechanical, and rheological properties, as well as the fracture surface morphology of the PLA/LG-g-PLMA composite films, were investigated. It was found that the compatibility and toughness of the composites were improved by the addition of ESO. The elongation at break of the composites with an ESO content of 5 phr was increased from 5.6% to 104.6%, and the tensile toughness was increased from 4.1 MJ/m3 to 44.7 MJ/m3, as compared with the PLA/LG-g-PLMA composite without ESO addition. The toughening effect of ESO on composites is generally attributed to the plasticization effect of ESO, and the interaction between the epoxy groups of ESO and the terminal carboxyl groups of PLA. Furthermore, PLA/LG-g-PLMA/ESO composite films exhibited excellent UV barrier properties and an overall migration value below the permitted limit (10 mg/dm2), indicating that the thus-prepared biocomposite films might potentially be applied to environmentally friendly food packaging.

[Tumor-Like Primary Central Nervous System Vasculitis With Spina Involvement:Report of One Case].

Primary central nervous system vasculitis (PACNS) is a vasculitic disorder affecting small to medium-sized blood vessels primarily in the central nervous system,involving the brain,spinal cord,and meninges.Tumor-like PNCAS,a rare subtype of PACNS,is often misdiagnosed as intracranial malignancy,and that with spinal cord involvement is even more uncommon.The lack of specific clinical symptoms and imaging manifestations poses a challenge to the diagnosis of PACNS.This report presents a case of tumor-like PACNS with spinal cord involvement based on the pathological evidence,aiming to enrich the knowledge about this condition.

Electrospun O-quaternary ammonium chitosan/polyvinyl alcohol nanofibrous film by application of Box-Behnken design response surface method for eliminating pathogenic bacteria.

In this study, O-quaternary ammonium chitosan (O-HTCC) containing bicationic antibacterial active groups was synthesized to develop an O-HTCC/PVA porous nanofibrous film to enhance antibacterial activity, leveraging surface modification and nano-porous structure design. Uniform and smooth nanofibrous structures (average diameter: 72-294 nm) were successfully obtained using a simple and feasible electrospinning method. A response surface model via Box-Behnken design (BBD) was used to clarify the interaction relationship between O-HTCC fiber diameter and three critical electrospinning parameters (O-HTCC concentration, applied voltage, feed flow rate), predicting that the minimum O-HTCC fiber diameter (174 nm) could be achieved with 7 wt% of O-HTCC concentration, 14 kV of voltage, and 0.11 mL/h of feed flow rate. Linear regression (R2 = 0.9736, Radj2 = 0.9716) and the Anderson Darling test demonstrated the excellent fit of the RSM-BBD model. Compared to N-HTCC/PVA nanofibrous film, the O-HTCC/PVA version showed increased growth inhibition and more effective antibacterial efficacies against Escherichia coli (E. coli) (~;86.34 %) and Staphylococcus aureus (S. aureus) (~;99.99 %). DSC revealed improved thermal stability with an increased melting temperature (238 °C) and endothermic enthalpy (157.7 J/g). This study holds potential for further development of antibacterial packaging to extend food shelf-life to reduce bacterial infection.

Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM.

Purpose: Type 2 diabetes mellitus (T2DM) is associated with multiple neuropsychiatric impairments, including cognitive dysfunction, and melatonin (MLT) plays a crucial role in maintaining normal neuropsychiatric functions. This study is aimed at investigating the change in plasma MLT levels and its association with neuropsychiatric impairments in T2DM patients. Methods: One hundred twenty-six T2DM patients were recruited, and their demographics and clinical data were collected. Apart from the plasma glycated hemoglobin (HbA1c) levels and other routine metabolic indicators, the plasma concentrations of MLT, C-reactive protein (CRP), Interleukin 6 (IL-6), soluble myeloid triggered receptor 1 (sTREM 1), and receptor 2 (sTREM 2) were measured. Moreover, the executive function and depressive tendency were evaluated via the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and the Epidemiological Research Center Depression Scale (CES-D), respectively. Result: Compared with the low HbA1c group, the T2DM patients in the high HbA1c group presented lower plasma MLT levels but higher plasma concentrations of inflammatory biomarker levels, together with higher scores in the BRIEF-A and CES-D scales. Moreover, results of the Pearson correlation test showed that the plasma MLT levels were negatively correlated with the BRIEF-A and CES-D scores, as well as plasma concentrations of HbA1c and inflammatory indications, indicating that MLT may mediate their neuroinflammation and neuropsychiatric impairments. Furthermore, the ROC curve results indicated that plasma MLT levels have a predictive effect on executive impairment and depressive status in T2DM patients. Conclusion: MLT levels decreased in patients with T2DM and were associated with neuropsychiatric impairments and inflammatory status, and MLT might be developed as a therapeutic agent and predictive indicator for T2DM-associated executive impairment and depression status.

Applications of MRI in Schizophrenia: Current Progress in Establishing Clinical Utility.

Schizophrenia is a severe mental illness that significantly impacts the lives of affected individuals and with increasing mortality rates. Early detection and intervention are crucial for improving outcomes but the lack of validated biomarkers poses great challenges in such efforts. The use of magnetic resonance imaging (MRI) in schizophrenia enables the investigation of the disorder's etiological and neuropathological substrates in vivo. After decades of research, promising findings of MRI have been shown to aid in screening high-risk individuals and predicting illness onset, and predicting symptoms and treatment outcomes of schizophrenia. The integration of machine learning and deep learning techniques makes it possible to develop intelligent diagnostic and prognostic tools with extracted or selected imaging features. In this review, we aimed to provide an overview of current progress and prospects in establishing clinical utility of MRI in schizophrenia. We first provided an overview of MRI findings of brain abnormalities that might underpin the symptoms or treatment response process in schizophrenia patients. Then, we summarized the ongoing efforts in the computer-aided utility of MRI in schizophrenia and discussed the gap between MRI research findings and real-world applications. Finally, promising pathways to promote clinical translation were provided. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Protective effectiveness of previous infection against subsequent SARS-Cov-2 infection: systematic review and meta-analysis.

Background: The protective effectiveness provided by naturally acquired immunity against SARS-CoV-2 reinfection remain controversial. Objective: To systematically evaluate the protective effect of natural immunity against subsequent SARS-CoV-2 infection with different variants. Methods: We searched for related studies published in seven databases before March 5, 2023. Eligible studies included in the analysis reported the risk of subsequent infection for groups with or without a prior SARS-CoV-2 infection. The primary outcome was the overall pooled incidence rate ratio (IRR) of SARS-CoV-2 reinfection/infection between the two groups. We also focused on the protective effectiveness of natural immunity against reinfection/infection with different SARS-CoV-2 variants. We used a random-effects model to pool the data, and obtained the bias-adjusted results using the trim-and-fill method. Meta-regression and subgroup analyses were conducted to explore the sources of heterogeneity. Sensitivity analysis was performed by excluding included studies one by one to evaluate the stability of the results. Results: We identified 40 eligible articles including more than 20 million individuals without the history of SARS-CoV-2 vaccination. The bias-adjusted efficacy of naturally acquired antibodies against reinfection was estimated at 65% (pooled IRR = 0.35, 95% CI = 0.26-0.47), with higher efficacy against symptomatic COVID-19 cases (pooled IRR = 0.15, 95% CI = 0.08-0.26) than asymptomatic infection (pooled IRR = 0.40, 95% CI = 0.29-0.54). Meta-regression revealed that SARS-CoV-2 variant was a statistically significant effect modifier, which explaining 46.40% of the variation in IRRs. For different SARS-CoV-2 variant, the pooled IRRs for the Alpha (pooled IRR = 0.11, 95% CI = 0.06-0.19), Delta (pooled IRR = 0.19, 95% CI = 0.15-0.24) and Omicron (pooled IRR = 0.61, 95% CI = 0.42-0.87) variant were higher and higher. In other subgroup analyses, the pooled IRRs of SARS-CoV-2 infection were statistically various in different countries, publication year and the inclusion end time of population, with a significant difference (p = 0.02, p < 0.010 and p < 0.010), respectively. The risk of subsequent infection in the seropositive population appeared to increase slowly over time. Despite the heterogeneity in included studies, sensitivity analyses showed stable results. Conclusion: Previous SARS-CoV-2 infection provides protection against pre-omicron reinfection, but less against omicron. Ongoing viral mutation requires attention and prevention strategies, such as vaccine catch-up, in conjunction with multiple factors.

Elucidating genetic and molecular basis of altered higher-order brain structure-function coupling in major depressive disorder.

Previous studies have shown that major depressive disorder (MDD) patients exhibit structural and functional impairments, but few studies have investigated changes in higher-order coupling between structure and function. Here, we systematically investigated the effect of MDD on higher-order coupling between structural connectivity (SC) and functional connectivity (FC). Each brain region was mapped into embedding vector by the node2vec algorithm. We used support vector machine (SVM) with the brain region embedding vector to distinguish MDD patients from health controls (HCs) and identify the most discriminative brain regions. Our study revealed that MDD patients had decreased higher-order coupling in connections between the most discriminative brain regions and local connections in rich-club organization and increased higher-order coupling in connections between the ventral attentional network and limbic network compared with HCs. Interestingly, transcriptome-neuroimaging association analysis demonstrated the correlations between regional rSC-FC coupling variations between MDD patients and HCs and α/ß-hydrolase domain-containing 6 (ABHD6), ß 1,3-N-acetylglucosaminyltransferase-9(ß3GNT9), transmembrane protein 45B (TMEM45B), the correlation between regional dSC-FC coupling variations and retinoic acid early transcript 1E antisense RNA 1(RAET1E-AS1), and the correlations between regional iSC-FC coupling variations and ABHD6, ß3GNT9, katanin-like 2 protein (KATNAL2). In addition, correlation analysis with neurotransmitter receptor/transporter maps found that the rSC-FC and iSC-FC coupling variations were both correlated with neuroendocrine transporter (NET) expression, and the dSC-FC coupling variations were correlated with metabotropic glutamate receptor 5 (mGluR5). Further mediation analysis explored the relationship between genes, neurotransmitter receptor/transporter and MDD related higher-order coupling variations. These findings indicate that specific genetic and molecular factors underpin the observed disparities in higher-order SC-FC coupling between MDD patients and HCs. Our study confirmed that higher-order coupling between SC and FC plays an important role in diagnosing MDD. The identification of new biological evidence for MDD etiology holds promise for the development of innovative antidepressant therapies.

Generation of an induced pluripotent stem cell line (CSBZZUi001-A) from a female Alzheimer's patient carrying the PSEN1 709 T > C heterozygous mutation.

Pluripotent stem cells were generated through the electroporation of episomal plasmids, containing crucial reprogramming factors, into skin fibroblasts extracted from a female Alzheimer's patient harboring the PSEN1 709 T > C (p.Phe237Leu) heterozygous mutation. The pluripotent stem cells exhibit a normal karyotype and express pivotal stem cell markers including TRA-1-60, Nanog, SOX2, and OCT4. Furthermore, their capacity to differentiate into the three germ layers in in vivo teratoma experiments has been substantiated. The pluripotent stem cell line can serve as a cellular model for Alzheimer's disease, offering significant value in elucidating the pathogenesis and therapeutic strategies of the disease.

The ratio of bone marrow myeloid progenitor cell proportion to mature lymphocytes proportion can effectively differentiate aplastic anemia and hypoplastic myelodysplastic syndrome and evaluate the quality of bone marrow aspirates.

INTRODUCTION: Aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (MDS-h) are bone marrow failure disease and difficult to distinguish merely by morphological analysis. In this study, we investigated the value of flow cytometry (FCM) in the differential diagnosis of AA and MDS-h. METHODS: We included 822 patients (626 control, 69 AA, 22 MDS-h and 105 dilution patients) from January 2017 to December 2022 for a retrospective study. Bone marrow myeloid progenitor (MP) cell and mature lymphocytes proportions were analyzed by FCM. The ratio of MP cell proportion and mature lymphocytes proportion, MPLR, was calculated. Data were compared by Kruskal-Wallis test. Differential diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. Cutoff value was determined by the maximum Youden index. RESULTS: Bone marrow MP cell proportion and MPLR of MDS-h patients were higher than AA patients. Mature lymphocytes proportion of MDS-h patients was lower than AA patients. Area under ROC curve (AUC of ROC) of MP cell proportion, MPLR and mature lymphocytes proportion to distinguish AA from MDS-h were 0.992, 0.988, and 0.850, respectively. Moreover, MPLR of dilution patients was higher than AA patients but lower than MDS-h patients. The AUC of ROC curves of MPLR to distinguish MDS-h and AA from dilution were 0.854 and 0.871, respectively. CONCLUSION: Bone marrow MP cell proportion and MPLR can effectively discriminate AA from MDS-h with similar differential efficacy, which is higher than mature lymphocytes proportion. Moreover, MPLR can evaluate the quality of bone marrow aspirates, which would interfere with the differential diagnosis.

A cryptic site in class 5 epitope of SARS-CoV-2 RBD maintains highly conservation across natural isolates.

The emergence of SARS-CoV-2 variants raises concerns about the efficacy of existing COVID-19 vaccines and therapeutics. Previously, we identified a conserved cryptic class 5 epitope of SARS-CoV-2 receptor binding domain (RBD) by two cross-neutralizing antibodies 7D6 and 6D6. Intriguingly, this site remains resistant to substantial mutations occurred in ever-changing SARS-CoV-2 subvariants. As compared to class 3 antibody S309, 6D6 maintains broad and consistent neutralizing activities against SARS-CoV-2 variants. Furthermore, 6D6 effectively protected hamster from the virulent Beta strain. Sequence alignment of approximately 6 million documented SARS-CoV-2 isolates revealed that 6D6 epitope maintains an exceptionally high conservation rate (99.92%). Structural analysis demonstrated that all 33 mutations accumulated in XBB.1.5 since the original strain do not perturb the binding 6D6 to RBD, in line with the sequence analysis throughout the antigenicity evolution of SARS-CoV-2. These findings suggest the potential of this epitope serving as a critical determinant for vaccines and therapeutic design.

Deubiquitination of CIB1 by USP14 promotes lenvatinib resistance via the PAK1-ERK1/2 axis in hepatocellular carcinoma.

Background: Lenvatinib is the most common multitarget receptor tyrosine kinase inhibitor for the treatment of advanced hepatocellular carcinoma (HCC). Acquired resistance to lenvatinib is one of the major factors leading to the failure of HCC treatment, but the underlying mechanism has not been fully characterized. Methods: We established lenvatinib-resistant cell lines, cell-derived xenografts (CDXs) and patient-derived xenografts (PDXs) and obtained lenvatinib-resistant HCC tumor tissues for further study. Results: We found that ubiquitin-specific protease 14 (USP14) was significantly increased in lenvatinib-resistant HCC cells and tumors. Silencing USP14 significantly attenuated lenvatinib resistance in vitro and in vivo. Mechanistically, USP14 directly interacts with and stabilizes calcium- and integrin-binding protein 1 (CIB1) by reversing K48-linked proteolytic ubiquitination at K24, thus facilitating the P21-activated kinase 1 (PAK1)-ERK1/2 signaling axis. Moreover, in vivo adeno-associated virus 9 mediated transduction of CIB1 promoted lenvatinib resistance in PDXs, whereas CIB1 knockdown resensitized the response of PDXs to lenvatinib. Conclusions: These findings provide new insights into the role of CIB1/PAK1-ERK1/2 signaling in lenvatinib resistance in HCC. Targeting CIB1 and its pathways may be a novel pharmaceutical intervention for the treatment of lenvatinib-resistant HCC.

Pseudouridine Detection and Quantification Using Bisulfite Incorporation Hindered Ligation.

Pseudouridine (Ψ) is a widespread RNA modification found in various RNA species, including rRNA, tRNA, snRNA, mRNA, and long noncoding RNA (lncRNA). Understanding the function of Ψ in these RNA types requires a robust method for the detection and quantification of the Ψ level at single-nucleotide resolution. A previously used method utilizes Ψ labeling by N-cyclohexyl-N'-ß-(4-methylmorpholinium)ethylcarbodiimide (CMC). The quantification of Ψ is based on the stop ratio after reverse transcription. However, the use of CMC followed by strong alkaline treatment causes severe RNA degradation, often requiring a large amount of RNA. The removal of CMC and recovery of RNA by ethanol precipitation are also time-consuming. Here, we introduce a Bisulfite Incorporation Hindered ligation-based method (BIHIND), which can detect and quantify Ψ sites on rRNA, mRNA, and noncoding RNA. BIHIND can be coupled with quantitative PCR (BIHIND-qPCR) for quantitative detection of Ψ fraction at individual modification sites, as well as with next-generation sequencing (BIHIND-seq) for high-throughput sequencing of Ψ without requiring reverse transcription. We validated the robustness of BIHIND with the elucidation of Ψ dynamics following pseudouridine synthase depletion.

Dataset of soil hydraulic parameters in the Yellow River Basin based on in situ deep sampling.

Soil hydraulic parameters are vital for precisely characterizing soil hydrological processes, which are critical indicators for regulating climate change effects on terrestrial ecosystems and governing feedbacks between water, energy, and carbon-nitrogen cycles. Although many studies have integrated comprehensive soil datasets, data quality and cost challenges result in data completeness deficiencies, especially for deep soil information. These gaps not only impede methodological endeavours but also constrain soil parameter-based ecosystem process studies spanning from local profiles to global earth system models. We established a soil dataset across the entire Yellow River Basin (YRB) (795,000 km2) using high-density in situ field sampling. This observation-based dataset contains records of soil texture (2924), bulk density (2798), saturated hydraulic conductivity (2782), and water retention curve parameters (1035) down to a maximum depth of 5 m. This dataset, which extends the recorded data range for deep soil hydraulic parameters, is valuable as a direct data resource for environmental, agronomical and hydrological studies in the YRB and regions with similar pedological and geological backgrounds around the world.

Efficacy and mechanism of the Ermiao San series of formulas for rheumatoid arthritis based on Chinmedomics strategy.

BACKGROUND: The Ermiao San Series of Formulas (ESSF) refers to Ermiao San (TS), Sanmiao Wan (TW), and Simiao Wan (FW), which are widely used traditional Chinese medicine (TCM) formulas for treating rheumatoid arthritis (RA). However, the therapeutic advantages and underlying mechanisms of ESSF treatment are unclear, especially regarding the improper selection of these three formulas when treating RA. PURPOSE: To explore the efficacy and mechanisms of ESSF treatment for RA. METHODS: Complete Freund's adjuvant was used to induce RA in rats. Chinmedomics strategy, which included metabolomics, serum pharmacochemistry of TCM, molecular docking, western blotting and qPCR, was applied to reveal the therapeutic advantages, pathways, and targets of ESSF. RESULTS: In the early stages of treatment, TS quickly reduced joint swelling and the arthritis score index and regulated pathways such as arachidonic acid metabolism and purine metabolism. TW increases the regulation of tryptophan metabolism and pyrimidine metabolism pathways, promoting the recovery of the thymus and spleen. FW increases the regulation of linoleic acid metabolism and has the greatest effect on immune organ and bone recovery. In addition, 54, 67, and 86 bioactive compounds were detected in the serum from TS, TW, and FW, respectively. Berberine, phellodendrine, atractylolide III, limonin, 25R-inokosterone, coixol, and stigmasterol were found to act on the key enzymes COX-2, mPGES-1, ALOX5, and XDH in arachidonic acid metabolism and purine metabolism pathways. Western blot and qPCR results showed that ESSF can reduce the activity of these targets, thereby inhibiting the expression of the inflammatory factors IL-1ß, IL-6, IL-17, and TNF-α; the tissue injury factors MMP-3 and CRP; and the rheumatoid factors CCP Ab and RF, thereby achieving anti-RA efficacy. CONCLUSION: ESSF has a good therapeutic effect on RA. TS focus on rapid swelling reduction in the early stages of RA, TW focus on the recovery of immune organ function, and FW can be used for bone recovery in the later stage of RA treatment. The key mechanism of treating RA is that ESSF reduces the activity of COX-2, mPGES-1, ALOX5, and XDH. These findings provide valuable guidance for targeted therapy for RA and for the clinical application of ESSF.

Correction: MicroRNA-329-3p inhibits the Wnt/ß-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1.

[This corrects the article DOI: 10.32604/or.2023.044085.].

Ultrasensitive detection of aggregated α-synuclein using quiescent seed amplification assay for the diagnosis of Parkinson's disease.

BACKGROUND: Seed amplification assays (SAA) enable the amplification of pathological misfolded proteins, including α-synuclein (αSyn), in both tissue homogenates and body fluids of Parkinson's disease (PD) patients. SAA involves repeated cycles of shaking or sonication coupled with incubation periods. However, this amplification scheme has limitations in tracking protein propagation due to repeated fragmentation. METHODS: We introduced a modified form of SAA, known as Quiescent SAA (QSAA), and evaluated biopsy and autopsy samples from individuals clinically diagnosed with PD and those without synucleinopathies (control group). Brain biopsy samples were obtained from 14 PD patients and 6 controls without synucleinopathies. Additionally, skin samples were collected from 214 PD patients and 208 control subjects. Data were analyzed from April 2019 to May 2023. RESULTS: QSAA successfully amplified αSyn aggregates in brain tissue sections from mice inoculated with pre-formed fibrils. In the skin samples from 214 PD cases and 208 non-PD cases, QSAA demonstrated high sensitivity (90.2%) and specificity (91.4%) in differentiating between PD and non-PD cases. Notably, more αSyn aggregates were detected by QSAA compared to immunofluorescence with the pS129-αSyn antibody in consecutive slices of both brain and skin samples. CONCLUSION: We introduced the new QSAA method tailored for in situ amplification of αSyn aggregates in brain and skin samples while maintaining tissue integrity, providing a streamlined approach to diagnosing PD with individual variability. The integration of seeding activities with the location of deposition of αSyn seeds advances our understanding of the mechanism underlying αSyn misfolding in PD.

Translocase of Outer Mitochondrial Membrane 40, as a Promising Biomarker for the Diagnosis of Polycystic Ovary Syndrome and Pan-Cancer.

Polycystic ovary syndrome (PCOS) is a metabolic disease that affects the reproductive system, and its pathogenesis remains unresolved. Through the application of bioinformatics and molecular biology techniques, this study has identified a significant association between translocase of outer mitochondrial membrane 40 (TOMM40) and both PCOS and pan-cancers. The selection of PCOS biomarkers included TOMM40, which we found to be significantly decreased in the PCOS group both in vitro and in vivo, using molecular biology methods such as Western Blot as well as immunohistochemistry. Over-expression TOMM40 can rescue the effect on apoptosis rate and proliferation suppression induced by DHEA in KGN cells. TOMM40 as a biomarker for the diagnosis of PCOS. The pan-cancer analysis revealed an association between elevated TOMM40 expression in Uterine Corpus Endometrial Carcinoma and an unfavorable prognosis, while increased TOMM40 expression in six tumor types was linked to a favorable prognosis. Therefore, TOMM40 can be regarded as a promising biomarker for diagnosing both PCOS and pan-cancer.

Case report: A patient with brachio-cervical inflammatory myopathy was misdiagnosed as flail arm syndrome.

Brachio-cervical inflammatory myopathy (BCIM) is a rare inflammatory myopathy characterized by dysphagia, bilateral upper limb atrophy, limb-girdle muscle weakness, and myositis-specific antibody (MSA) negativity. BCIM has a low incidence and is commonly associated with autoimmune diseases. We present a case report of a 55-year-old man with progressive upper limb weakness and atrophy, diagnosed with flail arm syndrome (FAS). The initial electromyography revealed extensive spontaneous muscle activity and increased duration of motor unit potentials (MUPs). During follow-up, evidence of myogenic damage was observed, as indicated by a decreased duration of MUPs in the right biceps muscle. Laboratory and genetic testing ruled out hereditary or acquired diseases. Negative serological antibodies for myasthenia gravis. Hereditary or acquired diseases were ruled out through laboratory and genetic testing. Whole-body muscle magnetic resonance imaging (MRI) showed extensive edema and fat replacement in the bilateral upper limbs, scapular, and central axis muscles, while the lower extremities were relatively mildly affected. Muscle biopsy revealed numerous foci of inflammatory cells distributed throughout the muscle bundle, with predominant CD20, CD138, and CD68 expression, accompanied by a light infiltration of CD3 and CD4 expression. The muscle weakness improved with the combination of oral prednisone (initially 60 mg/day, tapered) and methotrexate (5 mg/week) treatment.