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Background: Malignant pleural effusion is mostly a complication of advanced malignant tumors. However, the cancer markers such as carbohydrate antigen 125 (CA 125), carbohydrate antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), and cytokeratin fragment 21-1 (CYFRA 21-1) have low sensitivity and organ specificity for detecting malignant pleural effusion. Research question: Is IR808@MnO nano-near infrared fluorescent dye worthy for the diagnosis in differentiating benign and malignant pleural effusions. Study design and methods: This experiment was carried out to design and characterize the materials for in vitro validation of the new dye in malignant tumor cells in the A549 cell line and in patients with adenocarcinoma pleural effusion. The dye was verified to possess tumor- specific targeting capabilities. Subsequently, a prospective hospital-based observational study was conducted, enrolling 106 patients and excluding 28 patients with unknown diagnoses. All patients underwent histopathological analysis of thoracoscopic biopsies, exfoliative cytological analysis of pleural fluid, and analysis involving the new dye. Statistical analyses were performed using Microsoft Excel, GraphPad Prism, and the R language. Results: The size of IR808@MnO was 136.8 ± 2.9 nm, with peak emission at 808 nm, and it has near-infrared fluorescence properties. Notably, there was a significant difference in fluorescence values between benign and malignant cell lines (p < 0.0001). The malignant cell lines tested comprised CL1-5, A549, MDA-MB-468, U-87MG, MKN-7, and Hela, while benign cell lines were BEAS-2B, HUVEC, HSF, and VE. The most effective duration of action was identified as 30 min at a concentration of 5 μl. This optimal duration of action and concentration were consistent in patients with lung adenocarcinoma accompanied by pleural effusion and 5 μl. Of the 106 patients examined, 28 remained undiagnosed, 39 were diagnosed with malignant pleural effusions, and the remaining 39 with benign pleural effusions. Employing the new IR808@MnO staining method, the sensitivity stood at 74.4%, specificity at 79.5%, a positive predictive value of 69.2%, and a negative predictive value of 82.1%. The area under the ROC curve was recorded as 0.762 (95% CI: 0.652–0.872). The confusion matrix revealed a positive predictive value of 75.7%, a negative predictive value of 75.6%, a false positive rate of 22.5%, and a false negative rate of 26.3%. Interpretation: The IR808@MnO fluorescent probe represents an efficient, sensitive, and user-friendly diagnostic tool for detecting malignant pleural fluid, underscoring its significant potential for clinical adoption. [ABSTRACT FROM AUTHOR]

Cells are the basic unit of life. Electrochemical analysis of single cells/organelles is essential for uncovering the molecular mechanisms of physiological and pathological processes that are difficult to elucidate on a larger scale. This paper provides an overview of the commonly used fabrication methods for micro/nanoelectrodes applied in the investigations of single cells/organelles as well as the corresponding electrochemical measurements over the last four years including extracellular measurement, combination of extra and intracellular measurement, intracellular reactive oxygen species and reactive nitrogen species (ROS/RNS) measurement, and isolated organelles measurement. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the value of tissue inhibitors of MMPs-2 (TIMP-2) to indicate 5-Fluorouracil (5-Fu) resistance status in colorectal cancer. Methods: The 5-Fu resistance of colorectal cancer cell lines was detected using Cell-Counting Kit-8 (CCK-8) and calculated using IC50. Enzyme-linked immunosorbent assay (ELISA) and real time-quantitative polymerase chain reaction (RT-qPCR) were used to detect TIMP-2 expression level in the culture supernatant and serum. Twenty-two colorectal cancer patients' TIMP-2 levels and clinical characteristics were analyzed before and after chemotherapy. Additionally, the patient-derived xenograft (PDX) model of 5-Fu resistance was used to evaluate the feasibility of TIMP-2 as a predictive biomarker of 5-Fu resistance. Results: Our experimental results display that TIMP-2 expression is elevated in colorectal cancer drug-resistant cell lines, and its expression level is closely related to 5-Fu resistance. Moreover, TIMP-2 in colorectal cancer patient serum undergoing 5-Fu-based chemotherapy could indicate their drug resistance status, and its efficacy is higher than CEA and CA19-9. Finally, PDX model animal experiments reveal that TIMP-2 can detect 5-Fu resistance in colorectal cancer earlier than tumor volume. Conclusion: TIMP-2 is a good indicator of 5-Fu resistance in colorectal cancer. Monitoring the serum TIMP-2 level can help the clinician identify 5-Fu resistance in colorectal cancer patients earlier during chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is one of the most common cancers, which has a poor prognosis and is prone to recurrence and metastasis. DPP7 is a prolyl peptidase, which is an enzyme characterized by the feature of cleaving proline-containing peptides. We found that the expression level of DPP7 in CRC samples was significantly higher than that in adjacent non-tumor tissues by analyzing public colorectal cancer data and surgical specimens of CRC patients. Moreover, the increased expression of DPP7 is correlated with a higher stage of cancer and shorter overall survival, indicating the diagnostic value of DPP7 for CRC. Furthermore, functional annotations indicated that DPP7 is involved in neuroactive ligand–receptor interaction and olfactory transduction signaling. Our data demonstrated that DPP7 is a promising diagnostic and prognostic biomarker as well as a new therapeutic target for CRC. Colorectal cancer has a poor prognosis and is prone to recurrence and metastasis. DPP7, a prolyl peptidase, is reported to regulate lymphocyte quiescence. However, the correlation of DPP7 with prognosis in CRC remains unclear. With publicly available cohorts, the Wilcoxon rank-sum test and logistic regression were employed to analyze the relationship between DPP7 expression and the clinicopathological features of CRC patients. Specific pathways of differentially expressed genes were determined through biofunctional analysis and gene set enrichment analysis (GSEA). qPCR and immunohistochemical staining were used to determine DPP7 expression levels in surgical specimens. The public dataset and analysis of the biospecimens of CRC patients revealed that DPP7, in the CRC samples, was expressed significantly higher than in non-tumor tissues. Moreover, increased DPP7 was significantly associated with a higher N stage, lymphatic invasion, and shorter overall survival. Functionally, DPP7 is involved in neuroactive ligand–receptor interaction and olfactory transduction signaling. We identified a series of targeted drugs and small-molecule drugs with responses to DPP7. To conclude, DPP7 is a valuable diagnostic and prognostic biomarker for CRC and considered as a new therapeutic target. [ABSTRACT FROM AUTHOR]

The concept of submodularity has wide applications in data science, artificial intelligence, and machine learning, providing a boost to the investigation of new ideas, innovative techniques, and creative algorithms to solve different submodular optimization problems arising from a diversity of applications. However pure submodular problems only represent a small portion of the problems we are facing in real life applications. In this paper, we further discuss the two-stage submodular maximization problem under a ℓ -matroid constraint. We design an approximation algorithm with constant approximation ratio with respect to the curvature, which improves the previous bound. In addition, we generalize our algorithm to the two-stage submodular maximization problem under a ℓ -exchange system constraint. [ABSTRACT FROM AUTHOR]

Introduction: Pentraxin 3 (PTX3) is involved in inflammation regulation and has a certain association with infectious diseases. However, its specific correlation with infectious diseases remains controversial. This study aimed to analyze the association between them and explore the possible role of PTX3 in the prognosis of coronavirus disease 2019 (COVID-19). Methods: Five databases (PubMed, Cochrane Library, Embase, Clinicaltrials.gov, and gray literature) were searched. Outcomes were expressed as a standardized mean difference (SMD) and 95% confidence intervals (CI). The Newcastle–Ottawa Scale (NOS) was used to evaluate the quality of included articles. Stata 12 and Meta-DiSc were applied to analyze the pooled data. Receiver operating characteristic (ROC) curves were conducted to determine the prognostic value of PTX3 for mortality. Results: Six articles met the inclusion criteria. Circulating PTX3 levels had a nonsignificant difference between intensive care unit (ICU) and non-ICU patients with COVID-19 [SMD 1.37 (−0.08, 2.81); I2 = 93.9%, P < 0.01], while the PTX3 levels in nonsurvival COVID-19 patients was significantly lower than those in survival patients [SMD −1.41 (−1.92, −0.91); I2 = 66.4%, P = 0.051]. Circulating PTX3 had good mortality prediction ability (area under ROC curve, AUC = 0.829) in COVID-19. Funnel plots and Egger's tests showed low probabilities of publication bias. Through sensitivity analysis, the results of this study were robust. Conclusion: This study found that PTX3 was differentially expressed between survival and nonsurvival patients with COVID-19, while there was no significant difference between ICU and non-ICU patients. Meanwhile, circulating PTX3 may be a good biomarker for monitoring the prognosis of COVID-19, which may provide new ideas and directions for clinical and scientific research. Plain Language Summary: This study focuses on the relationship between circulating pentraxin 3 (PTX3) and coronavirus disease 2019 (COVID-19). COVID-19 can initiate the inflammatory reaction of the body, trigger a series of immune mechanisms, and cause death in severe cases. PTX3 is a soluble pattern recognition molecule (PRM) belonging to the humoral innate immune system, which may be increasingly deemed as an independent strong prognostic indicator in severe infectious diseases, such as COVID-19. Five databases (Pubmed, Cochrane Library, EMBASE, Clinicaltrials.gov, and gray literature) were searched for six keywords. There was no significant difference in circulating PTX3 levels between intensive care unit (ICU) and non-ICU patients with COVID-19, while the PTX3 levels of nonsurvival patients with COVID-19 was significantly lower than those of survival patients. Circulating PTX3 may indicate good diagnostic value in predicting the mortality of COVID-19, which may be useful as an indicator for monitoring. [ABSTRACT FROM AUTHOR]

Acute mastitis is one of the main reasons why breastfeeding women stop breastfeeding, and medication should be used with caution. Considering the uncertainty of mastitis infection and the indications of antibiotic use, as well as the problem of drug resistance and the safety of medication during lactation, probiotics have become an alternative treatment choice. However, a meta-analysis of the effects of probiotics in preventing and treating lactational mastitis is still lacking. Therefore, we searched six electronic databases and the sites of clinical trial registration, a total of six randomized controlled trials were included in this meta-analysis, which showed that oral probiotics during pregnancy can reduce the incidence of mastitis (RR: 0.49, 95% CI: 0.35 to 0.69; p<0.0001). After oral administration of probiotics, the counts of bacteria in the milk of healthy people and mastitis patients were both significantly reduced (in healthy people: MD: -0.19, 95% CI: -0.23 to -0.16, p<0.00001; in mastitis patients: MD: -0.89, 95% CI: -1.34 to -0.43, p = 0.0001). These indicate that to a certain extent, probiotics are beneficial in reducing the incidence rate of mastitis during lactation and some related mastitis symptoms. However, high-quality multicenter clinical trials are still needed to support this result. [ABSTRACT FROM AUTHOR]

Background and objective: The application of curcumin is limited by its instability. Mono‐carbonyl analogues of curcumin (MCACs) are structurally stable, yet the intermediate bridging ketones in their skeletons account for increased toxicity. This study aimed to synthesize and screen MCACs that exhibit low cytotoxicity and high antioxidant ability, and the effects of MCACs on experimental periodontitis were also investigated. Materials and methods: The cytotoxicity of MCACs on MC3 T3‐E1 was determined by MTT assay. The antioxidant capacity was investigated by the cell viability against H2O2‐induced damage and the level of reactive oxygen species (ROS) and malondialdehyde (MDA). The localization and protein expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) was detected by immunofluorescence and western blot, respectively. In addition, MCAC was intragastrically administrated in rats with ligature‐induced experimental periodontitis. The effects were assessed by bone resorption, as well as the immunohistology staining of inflammatory and oxidative stress markers. Results: MCACs with cyclopentanone and containing pyrone showed lower toxicity than natural curcumin were synthesized (1A‐10A, 1H‐10H), among which, 1A exhibited the most potent cytoprotective effect against H2O2‐induced damage. Such effects could be explained by the reduced MDA and ROS level, possibly through the nucleus translocation of Nrf2 and the induction of HO‐1. Micro‐CT results further indicated that 1A significantly reduced bone loss, along with an increased level of Nrf2 and HO‐1, and decreased TNF‐α and IL‐1β. Conclusion: The present study has synthesized a novel antioxidant MCAC 1A with good biosafety and stability. MCAC 1A could serve as a host response modulator with preventive and protective effects on periodontitis. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is a chronic infection initiated by oral bacterial and their virulence factors, yet the severity of periodontitis is largely determined by the dysregulated host immuno-inflammatory response. Baicalein is a flavonoid extracted from Scutellaria baicalensis with promising anti-inflammatory properties. This study aims to clarify the anti-inflammatory and osteogenic effects of baicalein in periodontal ligament cells (PDLCs) treated with lipopolysaccharides (LPS). Methods: Human PDLCs were incubated with baicalein (0–100 μM) for 2 h prior to LPS challenge for 24 h. MTT analysis was adopted to assess the cytoxicity of baicalein. The mRNA and protein expression of inflammatory and osteogenic markers were measured by real-time polymerase chain reaction (PCR), western blot and enzyme-linked immunosorbent assay (ELISA) as appropriate. Alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were performed to evaluate the osteogenic differentiation of PDLCs. The expression of Wnt/β-catenin and mitogen-activated protein kinase (MAPK) signaling related proteins was assessed by western blot. Results: MTT results showed that baicalein up to 100 μM had no cytotoxicity on PDLCs. Baicalein significantly attenuated the inflammatory factors induced by LPS, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), matrix metalloprotein-1 (MMP-1), MMP-2 and monocyte chemoattractant protein 1 (MCP-1) at both mRNA and protein level. Moreover, MAPK signaling (ERK, JNK and p38) was significantly inhibited by baicalein, which may account for the mitigated inflammatory response. Next, we found that baicalein effectively restored the osteogenic differentiation of LPS-treated PDLCs, as shown by the increased ALP and ARS staining. Accordingly, the protein and gene expression of osteogenic markers, namely runt-related transcription factor 2 (RUNX2), collagen-I, and osterix were markedly upregulated. Importantly, baicalein could function as the Wnt/β-catenin signaling activator, which may lead to the increased osteoblastic differentiation of PDLCs. Conclusions: With the limitation of the study, we provide in vitro evidence that baicalein ameliorates inflammatory response and restores osteogenesis in PDLCs challenged with LPS, indicating its potential use as the host response modulator for the management of periodontitis. [ABSTRACT FROM AUTHOR]

This work demonstrates a novel chemosensor, SPTPA, that exhibits fluorescence and colorimetric dual sensing of hypochlorite with an ICT ON strategy. Additionally, the chemosensor successfully detected and imaged endogenous hypochlorite in living cells, various types of bacteria, and zebrafish. [ABSTRACT FROM AUTHOR]

Background and objective: Bone remodeling during orthodontic treatment is achieved by the osteogenesis of human periodontal ligament cells (PDLCs) subjected to mechanical loadings. Transcriptional co‐activator with PDZ‐binding motif (TAZ) mediates bone remodeling in response to extracellular mechanical signals. This study aims to investigate the role of TAZ in osteogenesis of PDLCs under tensile strain. Materials and methods: A uniaxial cyclic tensile stress (CTS) at 12% elongation and 6 cycles/min (5 s on and 5 s off) was applied to PDLCs. The osteogenic differentiation was determined by the protein and gene expressions of osteogenic markers using qRT‐PCR and Western blot, respectively, and further by alkaline phosphatase (ALP) activity and Alizarin Red S staining. The interaction of TAZ with core‐binding factor α1 (Cbfα1) was examined by co‐immunoprecipitation. The immunofluorescence histochemistry was used to examine the nucleus aggregation of TAZ and the reorganization of actin filaments. Moreover, small interfering RNA‐targeting TAZ (TAZsiRNA) was used for TAZ inhibition and Y‐27632 was employed for Ras homologue‐associated coiled‐coil protein kinase (ROCK) signaling blockage. Results: CTS clearly stimulated the nucleus accumulation of TAZ and its interaction with Cbfα1. CTS‐induced osteogenesis in PDLCs was significantly abrogated by the infection with TAZsiRNA, as shown by the decreased stained nodules and protein expressions of Cbfα1, collagen type I, osterix, and osteocalcin, along with the inhibition of β‐catenin signaling. Moreover, ROCK inhibition by Y‐27632 hindered TAZ nucleus aggregation and its binding with Cbfα1, which subsequently lead to the decreased osteoblastic differentiation of PDLCs. Conclusions: Taken together, we propose that TAZ nucleus localization and its interaction with Cbfα1 are essential for the CTS‐induced osteogenic differentiation in PDLCs. And such TAZ activation by CTS could be mediated by ROCK signaling, indicating the pivot role of ROCK‐TAZ pathway for PDLCs differentiation. [ABSTRACT FROM AUTHOR]

Copper (Cu) is an important microelement for the maintenance of normal metabolism of dairy cows and a variety of enzymic composition. When Cu deficiency is occurred in dairy cows, it’ll be accompanied by many diseases. The main objective of the present study was to explore the correlation between Cu deficiency and oxidative stress of lactating dairy cows and evaluate early-warning index for Cu deficiency. There were divided into two groups based on serum Cu levels: a Cu deficiency group and a control group. Serum levels of ceruloplasmin (CP), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), and Cu were analysed. The results showed that CP levels in the Cu deficiency group were significantly lower than in the control group, while T-AOC levels were significantly higher, but there were no significant differences between SOD and GSH-PX levels. Pearson correlation analysis showed that serum CP levels were very significantly positively correlated with Cu deficiency, while serum T-AOC levels were very significantly negatively correlated and SOD and GSH-PX serum levels showed no correlations. Logistic regression analysis showed that CP was a risk factor for Cu deficiency, ROC analysis showed that CP had diagnostic value for Cu deficiency, with a critical value of 13.7 U/l. Hence, CP and T-AOC levels in lactating cows showed strong correlations to Cu deficiency, indicating that serum CP can be used to predict Cu deficiency. [ABSTRACT FROM AUTHOR]

The upper-level jet stream, a narrow band of maximum wind speed in the mid-latitude westerlies, exerts a considerable influence on the global climate by modulating the transport and distribution of momentum, heat and moisture. In this study by using four high-resolution models in the Paleoclimate Modelling Intercomparison Project phase 3, the changes of position and intensity of the northern hemisphere westerly jet at 200 hPa in summer during the mid-Holocene (MH), as well as the related mechanisms, are investigated. The four models show similar performance on the westerly jet. At the hemispheric scale, the simulated westerly jet has a poleward shift during the MH compared to the preindustrial period. The warming in arctic and cooling in the tropics during the MH are caused by the orbital changes of the earth and the precipitation changes, and it could lead to the weakened meridional temperature gradient and pressure gradient, which might account for the poleward shift of the westerly jet from the thermodynamic perspective. From the dynamic perspective, two maximum centers of eddy kinetic energy are simulated over the North Pacific and North Atlantic with the north deviation, which could cause the northward movement of the westerly jet. The weakening of the jet stream is associated with the change of the Hadley cell and the meridional temperature gradient. The largest weakening is over the Pacific Ocean where both the dynamic and the thermodynamic processes have weakening effects. The smallest weakening is over the Atlantic Ocean, and it is induced by the offset effects of dynamic processes and thermodynamic processes. The weakening over the Eurasia is mainly caused by the dynamic processes. [ABSTRACT FROM AUTHOR]