A candidate competitive ELISA based on monoclonal antibody 3A8 for diagnosis of contagious bovine pleuropneumonia.

For the development of a competitive ELISA (cELISA) to detect serum antibodies against the Mycoplasma mycoides subsp. Mycoides (Mmm) (strain PG1), the causative agent of contagious bovine pleuropneumonia (CBPP), all the proteins of this pathogen were analyzed. Then, a specific extracellular region of a transmembrane protein with the potential for diagnosis was identified. After that, a monoclonal antibody (Mab) named 3A8 was obtained using this extracellular region as an immunogen. Finally, a cELISA was established with the extracellular domain of this transmembrane protein as the coating antigen, Mab 3A8 as the competitive antibody, and HRP-labeled goat anti-mouse IgG as the enzyme-labeled antibody. This established method was used to detect the antibody dynamic regularity of goats which are artificially immunized Mmm and was also compared with a commercial ELISA kit. Further, the sera of 1011 different cattle from border provinces of China were monitored using a candidate Mab 3A8 cELISA. The detection results of known background sera used in this study indicate that a candidate diagnostic marker was successfully identified by analyzing all the coding proteins of Mmm in this research, and the cELISA established based on the Mab 3A8 against this protein can detect CBPP-positive serum with specificity and has no cross-reaction with other related epidemic disease-positive sera. In addition, we tested the sera collected from the border areas of China using the established ELISA, and no positive sample was detected. The research protocol of the CBPP cELISA established in this study is different from the traditional method, which can greatly reduce the investment of manpower and capital and save development time. We believe that this study's protocol could serve as a reference for the development of detection methods for mycoplasma and other complex pathogens. KEY POINTS: • A Mmm-specific diagnostic marker was obtained based on protein characteristics. • A cELISA was established for CBPP serum antibody detection. • The serological investigation was conducted for CBPP in the border areas of China.

Visible Light-Induced 1,2-Diphenyldisulfane-Mediated Defluoroborylation of Polyfluoroarenes.

A green and practical protocol of defluoroborylation of polyfluoroarenes with stable and readily accessible NHC-borane was developed, using 1,2-diphenyldisulfane as a hydrogen atom transfer (HAT) and single electron transfer (SET) reagent precursor under visible-light irradiation, leading to the concise formation of value-added fluorinated organoboron scaffolds. Mechanism studies revealed the method underwent a boryl radical addition reaction with polyfluoroarene, followed by successive single electron transfer pathways and defluorination of the C-F bond to offer the targeted product. This unprecedented platform relies on 1,2-diphenyldisulfane and base without using expensive photocatalysts, highlighting the methodology has promising application value to prepare borylated polyfluoroarene compounds.

Monocarboxylate transporter 4 protects against myocardial ischemia/reperfusion injury by inducing oxidative phosphorylation/glycolysis interconversion and inhibiting oxidative stress.

Myocardial ischemia/reperfusion (I/R) injury is the primary cause of heart damage in the treatment of myocardial infarction, and the imbalance of the energy metabolism in the pathogenesis of myocardial I/R is one of the main triggers of cardiac dysfunction. Monocarboxylate transporter 4 (MCT4) is a key transporter of lactate, which plays a vital role in cellular metabolism. The present study investigated the role and underlying mechanism of MCT4 in myocardial I/R injury. The results of this study showed that MCT4 was upregulated during oxygen-glucose deprivation (OGD) and restored after reoxygenation in cardiomyocytes HL-1. Interestingly, the overexpression of MCT4 increased cell viability and decreased apoptosis of OGD/R-induced HL-1 cells. Furthermore, MCT4 boosted glucose uptake and lactate levels and promoted protein expression of glycolysis regulator LDHA, while also impeding oxidative phosphorylation (OXPHOS) regulators C-MYC and NDUFB8 in OGD/R-induced HL-1 cells. A reduction in reactive oxygen species and oxidative stress markers malonaldehyde and superoxide dismutase was also observed within the OGD/R stimulated HL-1 cells. Additionally, the in vivo exogenous application of MCT4 restored cardiac function, as demonstrated by the reduced infarct size and decreased myocardial apoptosis in I/R rats. OXPHOS and oxidative stress declined, while glycolysis was activated when the I/R mice were injected with AAV-MCT4. Our findings indicate that MCT4 could exert a cardioprotective effect after myocardial I/R injury by inducing OXPHOS/glycolysis interconversion and inhibiting oxidative stress.

Association between ultrasound BI-RADS signs and molecular typing of invasive breast cancer.

Objective: To explore the correlation between ultrasound images and molecular typing of invasive breast cancer, so as to analyze the predictive value of preoperative ultrasound for invasive breast cancer. Methods: 302 invasive breast cancer patients were enrolled in Heping Hospital affiliated to Changzhi Medical College in Shanxi, China during 2020 to 2022. All patients accepted ultrasonic and pathological examination, and all pathological tissues received molecular typing with immunohistochemical (IHC) staining. The relevance between different molecular typings and ultrasonic image, pathology were evaluated. Results: Univariate analysis: among the four molecular typings, there were significant differences in tumor size, shape, margin, lymph node and histological grade (P<0.05). 1. Size: Luminal A tumor was smaller (69.4%), Basal -like type tumors are mostly larger (60.9%); 2. Shape: Basal-like type is more likely to show regular shape (45.7%); 3. Margin: Luminal A and Luminal B mostly are not circumscribed (79.6%, 74.8%), Basal -like type shows circumscribed(52.2%); 4. Lymph nodes: Luminal A type tends to be normal (87.8%), Luminal B type,Her-2+ type and Basal-like type tend to be abnormal (35.6%,36.4% and 39.1%). There was no significant difference in mass orientation, echo pattern, rear echo and calcification (P>0.05). Multivariate analysis: Basal-like breast cancer mostly showed regular shape, circumscribed margin and abnormal lymph nodes (P<0.05). Conclusion: There are differences in the ultrasound manifestations of different molecular typings of breast cancer, and ultrasound features can be used as a potential imaging index to provide important information for the precise diagnosis and treatment of breast cancer.

A method for extracting tumor events from clinical CT examination reports.

Accurate and efficient extraction of key information related to diseases from medical examination reports, such as X-ray and ultrasound images, CT scans, and others, is crucial for accurate diagnosis and treatment. These reports provide a detailed record of a patient's health condition and are an important part of the clinical examination process. By organizing this information in a structured way, doctors can more easily review and analyze the data, leading to better patient care. In this paper, we introduce a new technique for extracting useful information from unstructured clinical text examination reports, which we refer to as a medical event extraction (EE) task. Our approach is based on Machine Reading Comprehension (MRC) and involves two sub-tasks: Question Answerability Judgment (QAJ) and Span Selection (SS). We use BERT to build a question answerability discriminator (Judger) that determines whether a reading comprehension question can be answered or not, thereby avoiding the extraction of arguments from unanswerable questions. The SS sub-task first obtains the encoding of each word in the medical text from the final layer of BERT's Transformer, then utilizes the attention mechanism to identify important information related to the answer from these word encodings. This information is then input into a bidirectional LSTM (BiLSTM) module to obtain a global representation of the text, which is used, along with the softmax function, to predict the span of the answer (i.e., the start and end positions of the answer in the text report). We use interpretable methods to calculate the Jensen-Shannon Divergence (JSD) score between various layers of the network and confirm that our model has strong word representation capabilities, enabling it to effectively extract contextual information from medical reports. Our experiments demonstrate that our method outperforms existing medical event extraction methods, achieving state-of-the-art results with a notable F1 score.

Platelets Facilitate Wound Healing by Mitochondrial Transfer and Reducing Oxidative Stress in Endothelial Cells.

As a critical member in wound healing, vascular endothelial cells (ECs) impaired under high levels of reactive oxygen species (ROS) would hamper neovascularization. Mitochondria transfer can reduce intracellular ROS damage under pathological condition. Meanwhile, platelets can release mitochondria and alleviate oxidative stress. However, the mechanism by which platelets promote cell survival and reduce oxidative stress damage has not been clarified. Here, first, we selected ultrasound as the best method for subsequent experiments by detecting the growth factors and mitochondria released from manipulation platelet concentrates (PCs), as well as the effect of manipulation PCs on the proliferation and migration of HUVECs. Then, we found that sonicate platelet concentrates (SPC) decreased the level of ROS in HUVECs treated with hydrogen peroxide in advance, increased mitochondrial membrane potential, and reduced apoptosis. By transmission electron microscope, we saw that two kinds of mitochondria, free or wrapped in vesicles, were released by activated platelets. In addition, we explored that platelet-derived mitochondria were transferred to HUVECs partly by means of dynamin-dependent clathrin-mediated endocytosis. Consistently, we determined that platelet-derived mitochondria reduced apoptosis of HUVECs caused by oxidative stress. What is more, we screened survivin as the target of platelet-derived mitochondria via high-throughput sequencing. Finally, we demonstrated that platelet-derived mitochondria promoted wound healing in vivo. Overall, these findings revealed that platelets are important donors of mitochondria, and platelet-derived mitochondria can promote wound healing by reducing apoptosis caused by oxidative stress in vascular endothelial cells. And survivin is a potential target. These results further expand the knowledge of the platelet function and provide new insights into the role of platelet-derived mitochondria in wound healing.

Weakly acidic microenvironment of the wound bed boosting the efficacy of acidic fibroblast growth factor to promote skin regeneration.

The pH value within the wound microenvironment influences indirectly and directly all biochemical reactions taking place in the process of skin wound healing. Currently, it is generally believed that a low pH value, such as it is found on normal skin, is favorable for wound regeneration, while some investigations have shown that in fact alkaline microenvironments are required for some healing processes. The role of growth factors in promoting wound healing requires a specific microenvironment. In wound microenvironments of different pH, growth factors with different isoelectric points may have different effects. To explore whether the application of FGF with different isoelectric points in wounds with different pH values interferes with the healing process to different degrees, GelMA hydrogels with different pH values were prepared to maintain the wounds microenvironment with the same pH values, in which aFGF and bFGF were loaded as well. The results show that GelMA hydrogels of different pH values maintained the same pH of the wound microenvironment sustainably on the 4th day. Moreover, aFGF and bFGF promoted skin wound healing to varying degrees in different pH wound microenvironments. In particular, aFGF significantly promoted wound re-epithelialization in a weak acidic microenvironment, while bFGF promoted collagen synthesis and deposition in the early stage of weak acid wounds. In addition, aFGF plays a superior role in inhibiting inflammation in weak acidic wounds.

[Establishment and Application of Foshan Ozone Concentration Forecast Equation].

The formation and changes of ozone (O3), a secondary pollutant in the atmosphere, are complex, and ozone forecasting has become one of the current problems in air pollution prevention and control. In this study, the relationships between the near-surface O3 concentration and meteorological elements (high- and low-level) in Foshan from 2014 to 2017 were analyzed, and the concentration forecasting equation was established, tested, and applied. The results showed that the near-surface O3 changed closely related to high- and low-level meteorological elements. Meteorological elements such as temperature and sunshine hours were significantly positively correlated with O3 concentration, whereas relative humidity, total (low) cloud cover, and wind speed were negatively correlated with O3. Heavy O3 pollution often occurred with meteorological conditions of low wind speed, sunny days and few clouds, low relative humidity, longer sunshine time, and higher temperature. The definitions of high-concentration O3 potential index (HOPI) and wind direction index (WDI) in the Foshan area could better characterize the meteorological conditions of O3 pollution. Considering 13 meteorological elements, such as HOPI and WDI at different heights, the O3 concentration forecasting equation in the Foshan area was established using multi-indicator stacking and multiple stepwise regression methods. Using the 2018 data, it was found that the correlation coefficient R between the simulated values and the measured values reached 0.82, and the forecast equation had a good fitting effect and predictability.

A composite hydrogel containing resveratrol-laden nanoparticles and platelet-derived extracellular vesicles promotes wound healing in diabetic mice.

Diabetic wounds are difficult to heal because of persistent inflammation and limited angiogenesis. Resveratrol (RES) is an anti-inflammatory and antioxidant agent. Platelet-derived extracellular vesicles (PDEVs) are rich in growth factors and cytokines, which promote proliferation and angiogenesis. However, single drug treatment has limited efficacy and delivery efficiency. Bioengineering can improve the limited effect of single drugs by combining drugs and materials to obtain complementary or cooperative bioengineered drugs. In this study, gelatin methacrylate (GelMA) and silk fibroin glycidyl methacrylate (SFMA) were used to synthesize GelMA/SFMA composite hydrogels with suitable mechanical properties, swelling ratio and biodegradability. The composite hydrogel was used as a wound dressing for sustained drug release. RES was loaded into mesoporous silica nanoparticles (MSNs) to synthesize MSN-RES to enhance the release dynamic, and MSN-RES and PDEVs were combined with the composite hydrogels to form GelMA/SFMA/MSN-RES/PDEVs hydrogels. The GelMA/SFMA/MSN-RES/PDEVs had low cytotoxicity and good biocompatibility, inhibited macrophage iNOS expression, and promoted the tube formation by human umbilical vein endothelial cells (HUVECs) in vitro. In a diabetic mouse wound model, the GelMA/SFMA/MSN-RES/PDEVs hydrogels decreased the expression of pro-inflammatory factors TNF-α and iNOS, increased the expression of anti-inflammatory factors TGF-ß1 and Arg-1, promoted angiogenesis, and accelerated wound healing. Interestingly, the GelMA/SFMA/MSN-RES/PDEVs hydrogels promoted the expression of extracellular purinergic signaling pathway-related CD73 and adenosine 2A receptor (A2A-R). Therefore, the GelMA/SFMA/MSN-RES/PDEVs hydrogels could be used as wound dressings to regulate the inflammation and angiogenesis of diabetic wounds and accelerate wound healing. STATEMENT OF SIGNIFICANCE: Drugs often fail to function because of a continuous oxidative stress microenvironment and inflammation. Here, a GelMA/SFMA hydrogel, with enhanced mechanical properties and liquid absorption ability, is proposed for sustained release of drugs. In addition to carrying platelet-derived extracellular vesicles (PDEVs) with pro-angiogenic effects, the hydrogels were also loaded with nanoparticle-encapsulated resveratrol with anti-inflammatory activities, aiming to reduce inflammation and oxidative stress in the wound microenvironment, such that the wound could receive proliferative repair signals to achieve sequential treatment and heal quickly. We also experimentally predicted that the regulatory mechanism of the GelMA/SFMA/MSN-RES/PDEVs in wound healing might be related to the extracellular purinergic signaling pathway.

Long non-coding RNA SNHG16 promotes human placenta-derived mesenchymal stem cell proliferation capacity through the PI3K/AKT pathway under hypoxia.

BACKGROUND: The effect of hypoxia on mesenchymal stem cells (MSCs) is an emerging topic in MSC biology. Although long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) are reported to play a critical role in regulating the biological characteristics of MSCs, their specific expression and co-expression profiles in human placenta-derived MSCs (hP-MSCs) under hypoxia and the underlying mech anisms of lncRNAs in hP-MSC biology are unknown. AIM: To reveal the specific expression profiles of lncRNAs in hP-MSCs under hypoxia and initially explored the possible mechanism of lncRNAs on hP-MSC biology. METHODS: Here, we used a multigas incubator (92.5% N2, 5% CO2, and 2.5% O2) to mimic the hypoxia condition and observed that hypoxic culture significantly promoted the proliferation potential of hP-MSCs. RNA sequencing technology was applied to identify the exact expression profiles of lncRNAs and mRNAs under hypoxia. RESULTS: We identified 289 differentially expressed lncRNAs and 240 differentially expressed mRNAs between the hypoxia and normoxia groups. Among them, the lncRNA SNHG16 was upregulated under hypoxia, which was also validated by reverse transcription-polymerase chain reaction. SNHG16 was confirmed to affect hP-MSC proliferation rates using a SNHG16 knockdown model. SNHG16 overexpression could significantly enhance the proliferation capacity of hP-MSCs, activate the PI3K/AKT pathway, and upregulate the expression of cell cycle-related proteins. CONCLUSION: Our results revealed the specific expression characteristics of lncRNAs and mRNAs in hypoxia-cultured hP-MSCs and that lncRNA SNHG16 can promote hP-MSC proliferation through the PI3K/AKT pathway.

Translation and validation of the Chinese version of the orthorexia nervosa assessment questionnaires among college students.

PURPOSE: The main objective of the study was to translate, validate, and compare the Chinese ORTO scales (ORTO-15 and ORTO-R). The secondary objective was to assess factors that may be related with risk of orthorexia nervosa (ON). METHODS: Two cross-sectional surveys were conducted on March-to-June 2021 for ORTO-15 and April 2022 for ORTO-R. ORTO questionnaires were translated into Chinese using the forward-backward-forward method. Exploratory factor analysis (EFA), discriminant validity and confirmatory factor analysis (CFA) were used to examine the construct validity of the questionnaires. The internal consistency was assessed using the Cronbach alpha coefficient and the test-retest reliability. Multivariate linear regression analysis was used to explore potential factors related with ON scores. RESULTS: Totally, 1289 and 1084 eligible participants were included for assessment of ORTO-15 and ORTO-R, with the mean age of 20.9 ± 2.0 years and 21.0 ± 2.3 years. The internal consistency of Chinese ORTO-15 scale and ORTO-R scale were both satisfactory (α = 0.79, ICC = 0.79; α = 0.77, ICC = 0.82). However, all ORTO-15 models showed a poor fit using CFA whereas the ORTO-R was characterized by acceptable goodness-of-fit. Multivariate linear regression indicated that physical activities and mental disorders were positively associated with ON risk assessed by both ORTO-R and ORTO-15. CONCLUSION: The Chinese ORTO-R scale was a more reliable tool to screen for ON tendencies than the Chinese version of ORTO-15. Mental disorders and physical activities might be associated with the increased ON risk. LEVEL OF EVIDENCE: Level V (descriptive cross-sectional study).

Development and application of tricolor ratiometric fluorescence sensor based on molecularly imprinted nanoparticles for visual detection of dibutyl phthalate in seawater and fish samples.

A tricolor ratiometric fluorescence sensor was fabricated by mixing blue- and red-emission molecularly imprinted quantum dots (MIP-QDs) with green-emission quantum dots at the optimal ratio. The MIP-QDs were synthesized by coating CdSe/ZnS QDs in polymer by inverse microemulsion method. Compared with single-emission or dual-emission sensors, the tricolor ratiometric fluorescence sensor provided a wider range of color variations for visual DBP detection. The ratio fluorescence value I530/(I450 + I630) of the tricolor ratiometric fluorescence sensor linearly changed within the concentration of 2.0-20.0 × 103 µg/L DBP. The correlation coefficient was 0.9910, and the limits of detection were 1.0 µg/kg and 0.65 µg/L in fish and seawater, respectively. Meanwhile, the fluorescence color gradually changed from purple to plum to pink to salmon to yellowish green and finally to green. The recoveries of DBP in fish and seawater were 84.3 %-91.4 % and 88.3 %-110.3 %, respectively. Moreover, no obvious differences were observed between the detection results of the tricolor ratiometric fluorescence sensor and gas chromatography-tandem mass spectrometry. The tricolor ratiometric fluorescence sensor constructed herein provides an ideal choice for rapid and intuitive DBP detection in environmental and aquatic products.

Mycoplasma hyopneumoniae membrane protein Mhp271 interacts with host UPR protein GRP78 to facilitate infection.

The unfolded protein response (UPR) plays a crucial role in Mycoplasma hyopneumoniae (M. hyopneumoniae) pathogenesis. We previously demonstrated that M. hyopneumoniae interferes with the host UPR to foster bacterial adhesion and infection. However, the underlying molecular mechanism of this UPR modulation is unclear. Here, we report that M. hyopneumoniae membrane protein Mhp271 interacts with host GRP78, a master regulator of UPR localized to the porcine tracheal epithelial cells (PTECs) surface. The interaction of Mhp271 with GRP78 reduces the porcine beta-defensin 2 (PBD-2) production, thereby facilitating M. hyopneumoniae adherence and infection. Furthermore, the R1-2 repeat region of Mhp271 is crucial for GRP78 binding and the regulation of PBD-2 expression. Intriguingly, a coimmunoprecipitation (Co-IP) assay and molecular docking prediction indicated that the ATP, rather than the substrate-binding domain of GRP78, is targeted by Mhp271 R1-2. Overall, our findings identify host GRP78 as a target for M. hyopneumoniae Mhp271 modulating the host UPR to facilitate M. hyopneumoniae adherence and infection.

Treatment of Acute Wounds With Recombinant Human-Like Collagen and Recombinant Human-Like Fibronectin in C57BL/6 Mice Individually or in Combination.

Wound repair is accomplished by the interaction between the cells involved in the repair and the extracellular matrix (ECM). Collagen is the main component of ECM, which is involved in transduction of signal, transportation of growth factors and cytokines. Fibronectin (FN) is also an important ECM, which participates in the initiation of fibroblast cell (FC) and promotes adhesion, migration, proliferation and differentiation of target cells. Compared with natural protein, the recombinant protein prepared by artificial method has the advantages of poor immunogenicity, wide range of sources, low cost and high activity. In this study, we used recombinant human-like collagen (RHC) and recombinant human-like fibronectin (rhFN) to treat acute wounds in C57BL/6 mice individually or in combination, and explored their effects on wound healing. Our study confirmed that these two recombinant proteins could effectively promote the proliferation, migration and adhesion of FCs. Meanwhile, it could positively regulate the healing speed and quality of acute wounds, re-epithelialization, collagen deposition, inflammation and angiogenesis. Moreover, we proved that the combination of the two was better than the treatment alone. Consequently, it has a good prospect as a new tissue material in the field of skin repair.

Highly selective molecularly imprinted-electrochemiluminescence sensor based on perovskite/Ru(bpy)32+ for simazine detection in aquatic products.

A novel molecularly imprinted electrochemiluminescence (MIECL) sensor based on the luminescence of molecularly imprinted polymer-perovskite (MIP-CsPbBr3) layer and Ru(bpy)32+ was fabricated for simazine detection. MIP-CsPbBr3 layers were immobilized onto the surface of glassy carbon electrode as the capture and signal amplification probe, and Ru(bpy)32+ and co-reactant tripropylamine exhibited stronger electrochemiluminescence (ECL) emission. Under optimal conditions, the ECL signal of the MIECL sensor was linearly quenched, with the logarithm of simazine concentration ranging from 0.1 µg/L to 500.0 µg/L, correlation coefficient of 0.9947, and limit of detection of 0.06 µg/L. The practicality of the developed MIECL sensor method for simazine determination in aquatic samples was validated. Excellent recoveries of 86.5 %-103.9 % with relative standard deviation below 1.6 % were obtained for fish and shrimp samples at three different spiked concentrations. The MIECL sensor exhibited excellent selectivity, sensitivity, reproducibility, accuracy, and precision for simazine determination in actual aquatic samples.

Effectiveness of Nano Bioactive Glass Fiber Loaded with Platelet-Rich Plasma on Thermal Wound Healing Process in Rats.

In this study we evaluated the impact of topical application of bioactive glass fibers loaded PRP on a deep seconddegree thermal wound and its healing process sub-streaming molecular pathway of re-epithelialization. Wistar rats were randomly divided into four groups: normal control group, model group (deep second-degree thermal wound), PRP group, and PRP+nanobioactive glass fiber group. After treatment, the changes of wounds were observed daily. H&E staining was used to evaluate the pathological changes and also, qRT-PCR was used to detect the mRNA expression of KGF, IL-1, IL-6, IL-10, TGF-ß, EGF, VEGF, HIF-1α, integrin α3 and integrin ß1 in wound tissues. In the current study, we observed that PRP group and the PRP group basically re-epithelized on the 21st day. The wound healing rates of the PRP+nanobioactive glass fiber group and PRP group at each time point were higher than those in the model group, while there was no significant difference in wound healing rate between the PRP+nanobioactive glass fiber group and PRP group at each time point. H&E staining showed that the pathological scores of skin wound repairing in the PRP+nanobioactive glass fiber group on the 7th, 14th and 21st day were higher than that of in the model group. The qPCR results suggested the mRNA expression of IL-1, IL-6 and IL-10 in the PRP+nanobioactive glass fiber group and the PRP group were lower than those in the untreated group on the 14th day; the expression of VEGF and EGF mRNA were higher on the 3rd day; the mRNA expression of TGF-ß, HIF-1α showed a tendency of increasing first and decreasing then; integrin ß1 mRNA expression increased significantly, which was highest; integrin α3 mRNA expression was higher on day 3rd and 21th, respectively. The PRP+nanobioactive glass fibers and PRP can shorten the wound healing time and improve the healing quality mainly by promoting the wound epithelization through increasing the expression of EGF, VEGF, TGF-ß, HIF-1α, Integrin α3, and meanwhile increasing the release of Integrin ß1 and other mechanisms.

Accuracy of cytokeratin 19 fragment in the diagnosis of bladder cancer.

Aim: CYFRA21-1 is a biomarker of cancer and has a promising future in the diagnosis of bladder cancer. The purpose of this study was to assess the diagnostic accuracy of CYFRA21-1 for bladder cancer. Methods: We included articles from the Cochrane Library, Web of Science, PubMed and Embase. Meta-DiSc 1.4 and Stata 12.0 were used for data analysis. Results: Twenty-eight articles were analyzed, and the results are as follows: sensitivity, specificity, PLR, NLR, DOR and AUC were 0.69 (95% CI [0.67, 0.71]), 0.81 (95% CI [0.80, 0.83]), 5.99 (95% CI [4.42, 8.11]), 0.31 (95% CI [0.25, 0.38]), 24.58 (95% CI [15.15, 39.89]) and 0.8917, respectively. Conclusion: CYFRA21-1 has a high diagnostic efficiency for bladder cancer.

Ultrasensitive electrochemiluminescence sensor based on perovskite quantum dots coated with molecularly imprinted polymer for prometryn determination.

A highly effective molecularly imprinted electrochemiluminescence sensor was constructed for prometryn determination in environmental and biological samples by using perovskite quantum dots coated with a molecularly imprinted silica layer (MIP/CsPbBr3-QDs) as the recognition and response element. MIP/CsPbBr3-QDs were immobilized on a glassy carbon electrode (GCE) through electropolymerization, and the electrochemiluminescence (ECL) response of MIP/CsPbBr3-QDs could be motivated under the condition of H2O2 as co-reactant. ECL signal was selectively quenched with prometryn by hindering electron transfer and directly proportional to the logarithm of prometryn concentration (0.10-500.0 µg/L) with a correlation coefficient of 0.9960. Limits of detection in fish and seawater samples were 0.010 µg/kg and 0.050 µg/L, respectively. Excellent recoveries of 88.0%-106.0% were acquired for fish and seawater samples with a relative standard deviation below 4.2%. The constructed MIECL sensor based on MIP/CsPbBr3-QDs showed good stability, accuracy, and precision for sensitive detection of prometryn in aquaculture products and environmental samples.

[The role of semaphorin 4D in the mechanism of bisphosphonate-related osteonecrosis of the jaw in rats].

PURPOSE: To study the expression level of semaphorin 4D (Sema4D) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) and to explore its possible role in the occurrence of BRONJ. METHODS: BRONJ-like rat model was established by intraperitoneal injection of zoledronic acid assisted with tooth extraction. The maxillary specimens were extracted for imaging and histological examination, and bone marrow mononuclear cells(BMMs) and bone marrow mesenchymal stem cells(BMSCs) of each group were obtained in vitro for co-culture. Trap staining and counting were performed on monocytes after osteoclast induction. RAW264.7 cells were induced by osteoclast orientation under bisphosphonates(BPs) environment, and Sema4D expression was detected. Similarly, MC3T3-E1 cells and BMSCs were induced to osteogenic orientation in vitro, and the expression level of osteogenic and osteoclastic related genes ALP, Runx2, and RANKL was detected under the intervention of BPs, Sema4D and Sema4D antibody. Statistical analysis of the data was performed using GraphPad Prism 8.0 software. RESULTS: BRONJ-like rat model was successfully constructed. Two weeks after tooth extraction, the healing of the tooth extraction wound in the experimental group was significantly limited, and the tooth extraction wound was exposed. H-E staining results showed that regeneration of new bone in the extraction socket of the experimental group was significantly restricted, dead bone was formed, and the healing of the soft tissue was limited. The results of trap staining showed that the number of osteoclasts in the experimental group was significantly less than that in the control group. Micro-CT results showed that bone mineral density and bone volume fraction in the extraction socket of the experimental group were significantly lower than those of the control group. Immunohistochemical results showed that compared with the control group, the expression level of Sema4D in the experimental group was significantly increased. In vitro studies showed that compared with the control group, the osteoclast induction of BMMs in the experimental group was significantly lower than that in the control group. BMSCs in the experimental group significantly reduced the induction of osteoclasts. Osteoclastic induction experiments revealed that bisphosphonates could effectively inhibit the formation of osteoclasts, and the expression of Sema4D was significantly reduced. Osteogenic induction experiment found that Sema4D significantly reduced the expression of Runx2 and RANKL genes in osteoblasts, while the expression of ALP gene decreased and the expression of RANKL up-regulated after adding Sema4D antibody. CONCLUSIONS: BPs can interfere with normal bone healing time by up-regulating the expression of Sema4D in tissues, leading to coupling disorder between osteoclasts and osteoblasts with inhibition of the maturation of osteoclasts, thereby inhibiting the growth of osteoblasts. Differentiation and expression of related osteogenic factors mediate the development of BRONJ.

Hypoxia-inducible factor-1α-mediated upregulation of CD99 promotes the proliferation of placental mesenchymal stem cells by regulating ERK1/2.

BACKGROUND: As human placenta-derived mesenchymal stem cells (hP-MSCs) exist in a physiologically hypoxic microenvironment, various studies have focused on the influence of hypoxia. However, the underlying mechanisms remain to be further explored. AIM: The aim was to reveal the possible mechanisms by which hypoxia enhances the proliferation of hP-MSCs. METHODS: A hypoxic cell incubator (2.5% O2) was used to mimic a hypoxic microenvironment. Cell counting kit-8 and 5-ethynyl-20-deoxyuridine incorporation assays were used to assay the proliferation of hP-MSCs. The cell cycle was profiled by flow cytometry. Transcriptome profiling of hP-MSCs under hypoxia was performed by RNA sequencing. CD99 mRNA expression was assayed by reverse transcription-polymerase chain reaction. Small interfering RNA-mediated hypoxia-inducible factor 1α (HIF-1α) or CD99 knockdown of hP-MSCs, luciferase reporter assays, and the ERK1/2 signaling inhibitor PD98059 were used in the mechanistic analysis. Protein expression was assayed by western blotting; immunofluorescence assays were conducted to evaluate changes in expression levels. RESULTS: Hypoxia enhanced hP-MSC proliferation, increased the expression of cyclin E1, cyclin-dependent kinase 2, and cyclin A2, and decreased the expression of p21. Under hypoxia, CD99 expression was increased by HIF-1α. CD99-specific small interfering RNA or the ERK1/2 signaling inhibitor PD98059 abrogated the hypoxia-induced increase in cell proliferation. CONCLUSION: Hypoxia promoted hP-MSCs proliferation in a manner dependent on CD99 regulation of the MAPK/ERK signaling pathway in vitro.