Mitochondrial Dysfunction and Chronic Liver Disease.

Mitochondria are generally considered the powerhouse of the cell, a small subcellular organelle that produces most of the cellular energy in the form of adenosine triphosphate (ATP). In addition, mitochondria are involved in various biological functions, such as biosynthesis, lipid metabolism, oxidative phosphorylation, cell signal transduction, and apoptosis. Mitochondrial dysfunction is manifested in different aspects, like increased mitochondrial reactive oxygen species (ROS), mitochondrial DNA (mtDNA) damage, adenosine triphosphate (ATP) synthesis disorder, abnormal mitophagy, as well as changes in mitochondrial morphology and structure. Mitochondrial dysfunction is related to the occurrence and development of various chronic liver diseases, including hepatocellular carcinoma (HCC), viral hepatitis, drug-induced liver injury (DILI), alcoholic fatty liver (AFL), and non-alcoholic fatty liver (NAFL). In this review, we summarize and discuss the role and mechanisms of mitochondrial dysfunction in chronic liver disease, focusing on and discussing some of the latest studies on mitochondria and chronic liver disease.

Overexpression of miR-125a-5p Inhibits Hepatocyte Proliferation through the STAT3 Regulation In Vivo and In Vitro.

microRNAs (miRNAs) are critically involved in liver regeneration (LR). miR-125a-5p (miR-125a) is a tumor-suppressing miRNA, but its role in LR has not been studied. Our previous studies have proved that miR-125a was related to LR at the initiation phase, while the mechanism hepatocyte proliferation triggered by miR-125a in LR has been rarely evaluated. Herein, we mainly studied the molecular mechanism of miR-125a in triggering hepatocyte proliferation and the proliferation stage of LR. Firstly, a striking reduction of miR-125a was found at 24 h as well as 30 h following partial hepatectomy (PH) in rat liver tissue by miRNAs expression profiles as well as qRT-PCR analysis. Furthermore, in vitro, upregulation of miR-125a decreased proliferation as well as G1/S conversion, which promoted hepatocytes apoptosis. STAT3 was the target of miR-125a. In vivo, upregulation of miR-125a by tail vein injection of agomir inhibited LR index. Upregulation of miR-125a inhibited LR index and hepatocytes proliferation by STAT3/p-STAT3/JUN/BCL2 axis. In summary, these current discoveries indicated that miR-125a inhibited hepatocytes proliferation as well as LR by targeting STAT3 and via acting on the STAT3/p-STAT3/JUN/BCL2 axis.

Overview of MicroRNAs as Diagnostic and Prognostic Biomarkers for High-Incidence Cancers in 2021.

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) about 22 nucleotides in size, which play an important role in gene regulation and are involved in almost all major cellular physiological processes. In recent years, the abnormal expression of miRNAs has been shown to be associated with human diseases including cancer. In the past ten years, the link between miRNAs and various cancers has been extensively studied, and the abnormal expression of miRNAs has been reported in various malignant tumors, such as lung cancer, gastric cancer, colorectal cancer, liver cancer, breast cancer, and prostate cancer. Due to the high malignancy grade of these cancers, it is more necessary to develop the related diagnostic and prognostic methods. According to the study of miRNAs, many potential cancer biomarkers have been proposed for the diagnosis and prognosis of diseases, especially cancer, thus providing a new theoretical basis and perspective for cancer screening. The use of miRNAs as biomarkers for diagnosis or prognosis of cancer has the advantages of being less invasive to patients, with better accuracy and lower price. In view of the important clinical significance of miRNAs in human cancer research, this article reviewed the research status of miRNAs in the above-mentioned cancers in 2021, especially in terms of diagnosis and prognosis, and provided some new perspectives and theoretical basis for the diagnosis and treatment of cancers.

Enhanced production of seed oil with improved fatty acid composition by overexpressing NAD+ -dependent glycerol-3-phosphate dehydrogenase in soybean.

There is growing interest in expanding the production of soybean oils (mainly triacylglycerol, or TAG) to meet rising feed demand and address global energy concerns. We report that a plastid-localized glycerol-3-phosphate dehydrogenase (GPDH), encoded by GmGPDHp1 gene, catalyzes the formation of glycerol-3-phosphate (G3P), an obligate substrate required for TAG biosynthesis. Overexpression of GmGPDHp1 increases soybean seed oil content with high levels of unsaturated fatty acids (FAs), especially oleic acid (C18:1), without detectably affecting growth or seed protein content or seed weight. Based on the lipidomic analyses, we found that the increase in G3P content led to an elevated diacylglycerol (DAG) pool, in which the Kennedy pathway-derived DAG was mostly increased, followed by PC-derived DAG, thereby promoting the synthesis of TAG containing relatively high proportion of C18:1. The increased G3P levels induced several transcriptional alterations of genes involved in the glycerolipid pathways. In particular, genes encoding the enzymes responsible for de novo glycerolipid synthesis were largely upregulated in the transgenic lines, in-line with the identified biochemical phenotype. These results reveal a key role for GmGPDHp1-mediated G3P metabolism in enhancing TAG synthesis and demonstrate a strategy to modify the FA compositions of soybean oils for improved nutrition and biofuel.

Chemical Visualization of Sweat Pores in Fingerprints Using GO-Enhanced TOF-SIMS.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been used in imaging of small molecules (<500 Da) in fingerprints, such as gunshot residues and illicit drugs. However, identifying and mapping relatively high mass molecules are quite difficult owing to insufficient ion yield of their molecular ions. In this report, graphene oxide (GO)-enhanced TOF-SIMS was used to detect and image relatively high mass molecules such as poison, alkaloids (>600 Da) and controlled drugs, and antibiotics (>700 Da) in fingerprints. Detail features of fingerprints such as the number and distribution of sweat pores in a ridge and even the delicate morphology of one pore were clearly revealed in SIMS images of relatively high mass molecules. The detail features combining with identified chemical composition were sufficient to establish a human identity and link the suspect to a crime scene. The wide detectable mass range and high spatial resolution make GO-enhanced TOF-SIMS a promising tool in accurate and fast analysis of fingerprints, especially in fragmental fingerprint analysis.

Signaling pathways of liver regeneration: Biological mechanisms and implications.

The liver possesses a unique regenerative ability to restore its original mass, in this regard, partial hepatectomy (PHx) and partial liver transplantation (PLTx) can be executed smoothly and safely, which has important implications for the treatment of liver disease. Liver regeneration (LR) can be the very complicated procedure that involves multiple cytokines and transcription factors that interact with each other to activate different signaling pathways. Activation of these pathways can drive the LR process, which can be divided into three stages, namely, the initiation, progression, and termination stages. Therefore, it is important to investigate the pathways involved in LR to elucidate the mechanism of LR. This study reviews the latest research on the key signaling pathways in the different stages of LR.

Toward multidimensional information: A derivatization-free UHPLC-QqQ MS/MS method for amino acid components of fingerprint.

The analysis of fingerprint chemical composition is a meaningful way to excavate the multidimensional information of fingerprint, including the donor profiling information and the age of a fingerprint, which broadens the evidential values of fingerprint, especially for the partial and distorted fingerprint. But the research remains still in the pilot phases or is ongoing. Amino acids are the dominant organic substances in latent sweat fingerprint and influenced by many donor factors. Hence, their content reflects personal information of donors. Forensic science will be revolutionized if suspects can be individualized by their amino acid content. The diverse nature, distinct physicochemical properties, and ultra-micro levels of amino acids present in fingerprints make it hard to detect. A high sensitivity method for detecting and quantifying multiple amino acid components is required. UHPLC-QqQ MS/MS offers high sensitivity, high separation, simultaneous multicomponents detection, and no derivatization, making it an ideal method for detecting and analyzing amino acids in fingerprints. Therefore, in this study, we propose and validate an efficient UHPLC-QqQ MS/MS method for the extraction and analysis of 13 amino acids from fingerprint. We compared the results of amino acids of 10 different substrates and found that the inherent amino acids in most porous substrates would have been extracted along with the fingerprint amino acids, making them unsuitable for quantitative amino acid analysis. Instead, plastic sheets are ideal substrates for laboratory studies. Then, extensive experiments were conducted among 30 donors for multidimensional information analysis. The type of samples analyzed were eccrine-rich fingerprints. A Binary Logistic Regression (BLR) model was developed, and the female and male donors were successfully differentiated by amino acids in fingerprints. Two other mathematical models were also developed to verify the accuracy, and all three different mathematical models were able to identify donors of different genders with over 90% accuracy. This demonstrates that amino acids have the potential to provide more information for donors as metabolic markers. In the future, we will conduct a series of experiments to analyze more multidimensional information for individual identification by amino acid content in the fingerprint.

Sarcoidosis with Severe Bone Involvement: A Case Report and Literature Review.

Sarcoidosis is a systemic granulomatous disease of the lungs that commonly involves intrathoracic lymph nodes. Here, we report the case of a 68-year-old woman who complained of shortness of breath and had suffered from the enlargement of intrathoracic lymph nodes for 12 years, swelling of the right middle finger for 7 years, and nasal obstruction for 2 years. The damage to the phalange was aggravated continuously and a malignant lesion could not be excluded, thus leading to amputation of the right middle finger. Pathological data indicated chronic inflammatory granulomatous disease and anti-acid staining was negative. Examination of the paranasal sinuses indicated destruction of the sinonasal bone and the swollen mucosa. Combined with the elevated ratio of CD4+/CD8+ T cells in bronchoalveolar lavage fluid and other results, the patient was finally diagnosed with sarcoidosis and received corticosteroid therapy. The shortness of breath and abnormality of the nose were significantly improved after treatment. Our case demonstrated the process of differential diagnosis for systemic granulomatous diseases, indicating the necessity of corticosteroid therapy for systematic sarcoidosis.

TOF-SIMS study of latent fingerprints on challenging substrates with the aid of transfer films.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been applied in forensic science for fingerprint detection. However, due to limitations of the instrument, it is not always possible to directly sample fingerprints on certain substrates. In this report, we indirectly sampled fingerprints using transfer films. First, we optimized the experimental conditions and identified transfer films with better results. We then explored the feasibility of revealing fingerprints after transfer and successfully transferred and revealed the detailed features of fingerprints on several common objects that could not be directly sampled. Fingerprints transferred from smooth surfaces yield clearer feature details in ion images. Additionally, we analyzed the substances in the transferred fingerprints and detected components of morphine and MDMA(3,4-methylenedioxy-n-methylamphetamine). By combining feature details with identified chemical components, the identity of a person can be determined, linking suspects to the crime scene. This work provides a new approach for sample introduction in instrumental analysis, enabling TOF-SIMS to be applied in more scenarios.

Closed incision management with negative pressure wound therapy (CIM): biomechanics.

A novel closed incision management with negative pressure wound therapy (CIM) has been developed for convenient use with closed incisions that has the potential to be beneficial for patients at risk for postoperative complications. Incisions are typically under lateral tension. This study explored the biomechanical mechanisms by which integrity of the incisional closure is enhanced by CIM. CIM was hypothesized to affect local stresses around closed incisions in a beneficial manner. Finite element analyses (FEA) indicated that application of CIM decreased the lateral stresses ~50% around the incision and changed the direction of the stresses to a distribution that is typical of intact tissue. Bench evaluations corroborated findings that CIM significantly increased the force required to disrupt the closed incision by ~50% as compared with closure alone. In conclusion, using 2 FEAs and bench modeling, CIM was shown to reduce and normalize tissue stresses and bolster appositional forces at the incision.

Objective evaluation of similarity scores derived by Evofinder® system for marks on bullets fired from Chinese Norinco QSZ-92 pistols.

In recent years, many studies have been conducted in the field of firearm identification with the objective of providing an objective method of evaluating the comparison of cartridge cases. However, less attention has been paid to the objective evaluation of bullet comparisons. In this study, 1 000 registered Chinese Norinco QSZ-92 pistols were used, and a database of 2 996 bullets was constructed. Both the receiver operating characteristic (ROC) curve and the score-based likelihood ratio method were used to objectively evaluate the similarity scores derived by the Evofinder® system. The results indicate that this system has excellent ability to discriminate between the selected pistols. This paper proposes an objective evaluation method, which serves as a response to the ongoing debates regarding the foundation of the discipline.

Expression of S100A9 and KL-6 in common interstitial lung diseases.

ABSTRACT: By evaluating S100 calcium binding protein A9 (S100A9) and Klebs von den Lungen-6 (KL-6) expression in patients with 4 common interstitial lung diseases (ILDs), we aimed to investigate whether S100A9 or KL-6 can be of any value in the differential diagnosis of these ILDs and simultaneously signal the disease progression.We collected the data of patients diagnosed with the 4 ILDs and underwent fiber-optic bronchoscopy and BAL in the First Affiliated Hospital, China Medical University from January 2012 to December 2020. The data related to BGA, C-reactive protein, pulmonary function test, total number and fraction of cells, T lymphocyte subsets in bronchoalveolar lavage fluid (BALF), and the expression of S100A9 and KL-6 in BALF and serum were collected. We analyzed, whether S100A9 or KL-6 could serve as a biomarker for differential diagnosis between the 4 common ILDs; whether the levels of S100A9 and KL-6 correlated with each other; whether they were correlated with other clinical parameters and disease severity.This study included 98 patients, 37 patients with idiopathic pulmonary fibrosis (IPF), 12 with hypersensitivity pneumonitis, 13 with connective tissue disease-associated ILD, and 36 with sarcoidosis (SAR): stage I (18), stage II (9), stage III (5), and stage IV (4). The expression of KL-6 in BALF was significantly higher in IPF patients than other 3 groups (all P-value < .05). However, there was no significant difference in the levels of S100A9 in BALF and serum between the 4 groups (P-value > .05). The levels of S100A9 in BALF of IPF patients was positively and significantly correlated with KL-6 expression and the percentage of neutrophils in BALF (P-value < .05). Along with the stage increase of SAR patients, the level of S100A9 in BALF gradually increased, which was negatively and significantly correlated with the forced vital capacity/predicted, carbon monoxide diffusing capacity/predicted%, and PaO2 (all P-value < .05).The expression of KL-6 in BALF can be used as a biomarker to differentiate IPF from the other 3 common ILDs. While, this was not the case with expression of S100A9 in BALF and serum. However, the expression S100A9 in BALF is useful to indicate the progression of SAR. Thus, simultaneous measurement of KL-6 and S100A9 levels in BALF makes more sense in differential diagnosing of the 4 common ILDS.

Neutrophils in Bronchoalveolar Lavage Fluid Indicating the Severity and Relapse of Pulmonary Sarcoidosis.

BACKGROUND: Pulmonary sarcoidosis is a highly heterogeneous granulomatous disease without any specific symptoms and manifestations. Neutrophils in bronchoalveolar lavage fluid (BALF) have been proposed to indicate the severity and prognosis of pulmonary sarcoidosis, but this needs confirmation in patients from different populations due to the heterogeneity of the disease. This study aimed to determine the characteristics of patients with pulmonary sarcoidosis in northeastern China and to explore the relationship between neutrophils in BALF and the severity of pulmonary sarcoidosis. METHODS: We enrolled 432 patients who were diagnosed with pulmonary sarcoidosis in this retrospective study. The symptoms, extrapulmonary involvement, forced vital capacity percentage predicted (FVC % pred), and diffusing capacity of the lung for carbon monoxide percentage predicted (DLco % pred) were recorded. BAL was performed in 319 patients, and the results of a cellular examination of BALF were collected. A total of 123 patients who received corticosteroid treatment were followed up for at least 12 months, and the outcomes were recorded. RESULTS: Cough was the most common symptom, and cutaneous involvement was the most common extrapulmonary manifestation in 304 (70.4%) and 82 (19.0%) patients, respectively. The percentages of patients with high neutrophil counts in BALF (>3%) were higher at Stages 2 and 3 compared with Stages 0 and 1 (33.2 vs. 19.4%, p = 0.007), although the percentages of neutrophils in BALF showed no difference between patients at Stages 0, 1, 2, and 3. Patients with high neutrophil counts in BALF had lower FVC % pred compared with the other patients (79.5 ± 18.2 vs. 84.9 ± 14.5%, p = 0.025) and were prone to relapse after corticosteroids were tapered. High neutrophil counts in BALF were independently associated with relapse after corticosteroids were tapered in a binary logistic regression analysis (p = 0.027). CONCLUSIONS: Patients with pulmonary sarcoidosis lacked specific symptoms and manifestations. The neutrophil count in BALF could indicate the severity and outcomes of pulmonary sarcoidosis.

Visualization of latent fingermarks on fabric using multi-metal deposition (MMD)-A preliminary study.

Multi-metal deposition (MMD) is a versatile fingermarks detection technique adapted from the colloidal gold biolabeling. However, the tedious procedures of MMD makes it receive little attention compared with other methods. The aim of this study is to evaluate the efficacy of MMD technique on several common fabrics, which is considered notoriously challenging for latent fingermark detection. Four different MMD formulations were examined to process fingermarks deposited on nylon taffeta, polyester taffeta, polyester pongee and cotton sateen to determine the most suitable one and the influence of aging and water immersion were also determined through subsequent experiments. It was found that MMD I outperformed other three formulations and obtained excellent results on nylon taffeta, polyester taffeta and satin ribbon, with polyester taffeta and satin ribbon providing more than 30% of identifiable marks even for fingermarks aged over 28 days. Cotton sateen and oxford cloth failed to produce ridge details but evidence of "touch" were successfully visualized, which may contribute to further DNA extraction. Water immersion did have some observable influence on the quality of detected marks as part of the MMD reactant within fingermarks lost during immersion, but the result from nylon taffeta and satin ribbon is still satisfying with the percentage of marks scored 3 and 4 reached 30%. The result of this study confirmed the capability of MMD I in treated with fingermarks on several kinds of fabrics, and shows potential to promote this non-instrumentation dependent technique.

Effect of carrier solvent in 1,2-indanedione formulation on the development of fingermarks on porous substrates.

As an important technique for the detection of fingermarks on porous surfaces, 1,2-indanedione is widely used due to its excellent detection performance. In order to optimize the effectiveness of 1,2-indanedione, several institutions have modified the original formulation. In this study, four different 1,2-indanedione formulations were used to treat fingermarks deposited on different porous substrates to determine the most suitable formulation and whether Solstice-PF can be an alternative carrier solvent for the currently used HFE7100. It was found that the Solstice-PF-based formulation performed similarly to the HFE7100-based formulation on copy paper, but when treating fingermarks deposited on brown paper and newspaper, Solstice-PF was superior to HFE7100 by developing up to 10% more marks graded 3 and 4 regardless of the ageing period. The results confirm that Solstice-PF can be used as an alternative carrier solvent for 1,2-indanedione formulations with good detection rates and lower costs.

Expression and Significance of HPV16 E6/E7 mRNAs in the Bronchial Brush and TBNA Cells of Patients With Small Cell Lung Cancer.

BACKGROUND AND OBJECTIVE: Small cell lung cancer (SCLC) is characterized by rapid growth, strong invasion, and early metastasis. However, the cause of its occurrence remains unclear. High-risk HPV infection is closely related to the occurrence of non-small cell lung cancer and cervical small cell neuroendocrine carcinoma. METHODS: The expression levels of E6 mRNA and E7 mRNA in HPV16 were detected by qRT-PCR in the bronchial brushing and transbronchial needle aspiration (TBNA) of 310 patients with lung cancer and with benign lung diseases. To make the design of this experiment scientific and reasonable, the expression levels in lung squamous cell carcinoma were taken as positive controls, while those in benign cells were taken as negative controls. RESULTS: The expression levels of E6 mRNA and E7 mRNA in SCLC group were significantly higher than those in benign cell group and slight higher than those in squamous cell carcinoma group. The expression levels of E6 mRNA and E7 mRNA in the central type of SCLC were significantly higher than those in the peripheral type of SCLC. CONCLUSIONS: We speculate that the occurrence of some small cell carcinoma is the same as that of some squamous cell carcinoma, which is closely related to HPV16 infection. The overexpression of E6 mRNA and E7 mRNA is in some benign lesion cells, which may be related to HPV transient infection.

Real-life experiences in a single center: efficacy of pirfenidone in idiopathic pulmonary fibrosis and fibrotic idiopathic non-specific interstitial pneumonia patients.

BACKGROUND: Pirfenidone is the first antifibrotic drug approved for the treatment of idiopathic pulmonary fibrosis (IPF) and it is used in the treatment of other interstitial pneumonias, such as unclassifiable interstitial lung disease (ILD) and connective tissue-related ILD. This study examined the efficacy of pirfenidone in patients with IPF and fibrotic idiopathic non-specific interstitial pneumonia (f-iNSIP). METHODS: In a retrospective real-life study, 67 IPF and 24 f-iNSIP patients were enrolled and classified into a pirfenidone group and a non-antifibrotic group. The level of forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLco) at baseline, 6, 12 and 24 months were recorded. The level of KL-6 in serum was detected by chemiluminescence enzyme immunoassay (CLEIA). The prognosis and safety outcomes were collected from patients. RESULTS: In IPF patients, pirfenidone decreased the mean change of FVC and DLco, and decreased the proportion of patients with a ⩾10% decline in FVC or a ⩾15% decline in DLco compared with the non-antifibrotic group. There was no difference in the mean change of FVC and DLco between smokers and non-smokers who received pirfenidone treatment. There was an improvement in progression-free survival, defined as the time to the first occurrence of acute exacerbation or death related to pulmonary fibrosis. Moreover, the ratio of patients who experienced acute exacerbation and death related to pulmonary fibrosis was lower in the pirfenidone group. There was no change in lung function and prognosis between the pirfenidone and non-antifibrotic groups in f-iNSIP patients. The KL-6 level slightly decreased after 1 year of pirfenidone treatment but not significantly. Gastrointestinal and skin-related adverse events were most common, and four patients ceased treatment due to the side effects. CONCLUSIONS: Pirfenidone safely reduced disease progression by improving the lung function and progression-free survival in IPF patients, with acceptable side effects. The efficacy of pirfenidone on f-iNSIP was not significant, suggesting the need for further studies.The reviews of this paper are available via the supplemental material section.

The Morphological Analysis of Cells in the Bronchoscopic Brushing and TBNA of Patients with Lung Adenocarcinoma.

Biopsy, brushing, and transbronchial needle aspiration (TBNA) are the most common methods for diagnosis of lung adenocarcinoma and are taken during the same diagnostic bronchoscopic procedure. However, it is not clear what the morphological diagnostic criteria of cytology by brushing or TBNA are. A retrospective analysis was performed on 136 patients who underwent video bronchoscopy examination for diagnostic purposes. All the subjects were performed brushing or TBNA and confirmed as lung adenocarcinoma by biopsy or postoperative pathology. An additional 140 randomly selected patients with benign lung diseases were included in the study and used as a control group. The benign cells usually confused with adenocarcinoma cells were ciliated columnar cells, mucous columnar cells, ciliated cuboid cells, and reactive ciliated cells, respectively. The number of cases diagnosed as adenocarcinoma cells, carcinoma cells, suspicious cancer cells, and atypical proliferative cells by cytology was 101, 11, 20, and 4, respectively. The main basis for the interpretation of adenocarcinoma cells is the enlargement of individual nucleus, the arrangements of multistage papillary, and the general enlargement of nuclei, while the main clue for the interpretation of suspicious cancer cells and dysplasia cells comes from escape cells. The results suggested that the degree of nuclear enlargement, multiple papillary arrangement, and escape cells or escape trend cells are important clues for the interpretation of lung adenocarcinoma cells, while the atypical proliferative cells were similar to escape cells or escape trend cells, which were essentially benign cells beside the cancer.

Distinct miRNA Gene Expression Profiles Among the Nodule Tissues of Lung Sarcoidosis, Tuberculous Lymphadenitis and Normal Healthy Control Individuals.

Background: Sarcoidosis and tuberculosis share similarities in clinical manifestations and histopathological features. We aimed to identify the microRNA (miRNA) profiles of the lymph nodes of individuals with sarcoidosis and of those with tuberculous lymphadenitis to investigate the value of miRNAs in the differential diagnosis of sarcoidosis and tuberculous lymphadenitis. Methods: The miRNA profiles of the lymph nodes of individuals with sarcoidosis, those with tuberculous lymphadenitis (TBLN) and controls were detected by miRNA microarray analysis in the age- and sex-matched development group of the controls (n = 3), patients with TBLN (n = 3) and patients with sarcoidosis (n = 3), and the results were validated by quantitative real-time polymerase chain reaction in the validation group of the controls (n = 30), TBLN (n = 30) and patients with sarcoidosis (n = 31). The relationship between miRNA expression and the clinical parameters of sarcoidosis was analyzed. Results: miR-145, miR-185-5p, miR-301, miR-425-5P, miR-449b and miR-885-5P were differentially expressed between individuals with sarcoidosis and controls (P < 0.0001, P < 0.0001, P = 0.0008, P = 0.0002, P = 0.0018, and P < 0.0001, respectively), and the same six miRNAs were differentially expressed between individuals with tuberculous lymphadenitis and controls (P = 0.0002, P = 0.0004, P = 0.0238, P = 0.0006, P = 0.0149, and P = 0.0045, respectively). miR-185-5p was differentially expressed between individuals with tuberculous lymphadenitis and those with sarcoidosis (P = 0.0101). The area under the receiver operating characteristic curve calculated for miR-185-5p was 0.6860, and the sensitivity and specificity of miR-185-5p for the differential diagnosis of sarcoidosis from TBLN were 61 and 80%, respectively. The levels of miR-145, miR-301, miR-425-5P, and miR-885-5P were positively correlated with CD4+/CD8+ T lymphocytes in bronchoalveolar lavage fluid. Conclusions: miRNAs in lymph nodes show similar expression patterns between individuals with sarcoidosis and those with tuberculous lymphadenitis, which were experimentally selected. miR-185-5p in the lymph nodes can be used as an auxiliary marker for the differential diagnosis of sarcoidosis and tuberculous lymphadenitis.

Exploiting the divergent reactivity of aryl-palladium intermediates for the rapid assembly of fluorene and phenanthrene derivatives.

They all fall down: The value of domino processes can be greatly enhanced when the possibility exists for one to selectively diverge from a common intermediate. In preliminary studies the dual reactivity of aryl-palladium intermediates is exploited. A diverse array of fluorene and phenanthrene derivatives were synthesized in a rapid and efficient manner (see scheme).