Activation of the HMGB1-TLR4 pathway impacts the functionality of bone marrow mesenchymal stem cells and disrupts macrophage polarization in immune thrombocytopenia.

Recent evidence suggests that immune thrombocytopenia (ITP), a common bleeding disorder, is linked to an imbalance in macrophage polarization and impaired bone marrow mesenchymal stem cells (BMSCs). However, the relationship between macrophage polarization imbalance and functional defects in BMSCs, as well as the involvement of associated molecules in BMSCs' defects, is not well understood. This study aimed to investigate the regulatory effects of high mobility group protein 1 (HMGB1) on the physiological functions of BMSCs, specifically in relation to macrophage polarization imbalance. Patients with ITP showed dysregulation in monocyte/macrophage polarization and impaired BMSCs function. HMGB1 was found to have a negative impact on the ability of BMSCs to regulate the imbalance in macrophage polarization, especially when inflammatory factors are present. The MyD88-dependent pathway downstream of BMSCs was found to be significantly enhanced with HMGB1 treatment. Furthermore, treatment with toll-like receptor 4 (TLR4) inhibitors successfully restored the regulatory capacity of BMSCs in ameliorating macrophage polarization imbalance and effectively inhibited the activation of the MyD88-dependent pathway. Meanwhile, infusion of si-TLR4-BMSCs reversed HMGB1-induced platelet dysfunction and reduced over-polarization to M1-like macrophages in the ITP mouse model. Consequently, targeting the HMGB1-TLR4 pathway could be a potential approach to restore the immunoregulatory function of BMSCs.

Identification of Microorganism in Infected Wounds by Positively Charged Selective Sensor Array and Deep Learning Algorithm.

Microorganism are ubiquitous and intimately connected with human health and disease management. The accurate and fast identification of pathogenic microorganisms is especially important for diagnosing infections. Herein, three tetraphenylethylene derivatives (S-TDs: TBN, TPN, and TPI) featuring different cationic groups, charge numbers, emission wavelengths, and hydrophobicities were successfully synthesized. Benefiting from distinct cell wall binding properties, S-TDs were collectively utilized to create a sensor array capable of imaging various microorganisms through their characteristic fluorescent signatures. Furthermore, the interaction mechanism between S-TDs and different microorganisms was explored by calculating the binding energy between S-TDs and cell membrane/wall constituents, including phospholipid bilayer and peptidoglycan. Using a combination of the fluorescence sensor array and a deep learning model of residual network (ResNet), readily differentiation of Gram-negative bacteria (G-), Gram-positive bacteria (G+), fungi, and their mixtures was achieved. Specifically, by extensive training of two ResNet models with large quantities of images data from 14 kinds of microorganism stained with S-TDs, identification of microorganism was achieved at high-level accuracy: over 92.8% for both Gram species and antibiotic-resistant species, with 90.35% accuracy for the detection of mixed microorganism in infected wound. This novel method provides a rapid and accurate method for microbial classification, potentially aiding in the diagnosis and treatment of infectious diseases.

Empathy in undergraduate medical students: a multi-center cross-sectional study in China.

BACKGROUND: Fostering empathy has been continuously emphasized in the global medical education. Empathy is crucial to enhance patient-physician relationships, and is associated with medical students' academic and clinical performance. However, empathy level of medical students in China and related influencing factors are not clear. METHODS: This was a cross-sectional study among medical students in 11 universities. We used the Jefferson Scale of Empathy Student-version of Chinese version to measure empathy level of medical students. Factors associated with empathy were identified by the univariate and multivariate logistic regression analyses. Based on the variables identified above, the nomogram was established to predict high empathy probability of medical students. Receiver operating characteristic curve, calibration plot and decision curve analysis were used to evaluate the discrimination, calibration and educational utility of the model. RESULTS: We received 10,901 samples, but a total of 10,576 samples could be used for further analysis (effective response rate of 97.02%). The mean empathy score of undergraduate medical students was 67.38 (standard deviation = 9.39). Six variables including gender, university category, only child or not, self-perception doctor-patient relationship in hospitals, interest of medicine, Kolb learning style showed statistical significance with empathy of medical students (P < 0.05). Then, the nomogram was established based on six variables. The validation suggested the nomogram model was well calibrated and had good utility in education, as well as area under the curve of model prediction was 0.65. CONCLUSIONS: We identify factors influencing empathy of undergraduate medical students. Moreover, increasing manifest and hidden curriculums on cultivating empathy of medical students may be needed among medical universities or schools in China.

A multicenter cross-sectional study in China revealing the intrinsic relationship between medical students' grade and their perceptions of the learning environment.

BACKGROUND: Medical school learning environment (MSLE) has a holistic impact on students' psychosomatic health, academic achievements, and personal development. Students in different grades perceive MSLE in different ways. Thus, it is essential to investigate the specific role of student's grade in the perception of MSLE. METHODS: Using the Johns Hopkins Learning Environment Scale (JHLES) as a quantification instrument for the perception level of MSLE, 10,901 medical students in 12 universities in China were categorized into low or high JHLES group according to their questionnaires. We investigated the relationship between student's grade and JHLES category by univariate analysis employing Pearson Chi-square test and Welch's ANOVA. Then multivariable logistic regression analysis confirmed the predictive efficacy of student's grade. A nomogram concerning the prediction of low JHLES score probability in medical students was also constructed. RESULTS: A significant difference between two JHLES categories among students in different grades was observed (p < 0.001), with the proportion of the high JHLES group dominating in grade 1, 5, and the graduate subgroups (p < 0.001). The mean JHLES score declined especially in the third and fourth graders compared to freshmen (p < 0.001), while the mean score among the fifth graders had a remarkable rebound from the third graders (p < 0.001). Most imperatively, identified by multivariable logistic regression analysis, students in grade 3 (OR = 1.470, 95% CI = 1.265-1.709, p < 0.001) and 4 (OR = 1.578, 95% CI = 1.326-1.878, p < 0.001) perceived more negatively than freshmen. The constructed nomogram provided a promising prediction model for student's low JHLES score probability, with accuracy, accordance, and discrimination (area under the curve (AUC) = 0.627). CONCLUSION: The student's grade was a significant influencing factor in medical students' perception of MSLE. The perceptions among the third and fourth graders got worse, probably due to the worrying changes in various aspects of MSLE during that period. The relevant and appropriate interventions to improve medical students' perceptions are urgently needed.

Interprofessional collaboration in primary care for patients with chronic illness: a scoping review protocol mapping leadership and followership.

Effective interprofessional collaboration (IPC) in primary care is essential for providing high-quality care for patients with chronic illness. However, the traditional role-based leadership approach in which physicians are the sole leaders, may hinder IPC. To improve IPC, leadership roles may need to shift dynamically based on expertise and experience, allowing for fluid transitions between leaders and followers within teams. Until now, most studies exploring this phenomenon focus on secondary care settings where teamwork is often physician-led, protocol-driven, and time-limited. Our understanding of followership in primary care remains limited. Therefore, we present a protocol for a scoping review to map the research on leadership and followership within IPC in primary care settings for patients with chronic illness and relevant training interventions within this context. An electronic search will be conducted across PubMed, Embase, and Web of Science to identify studies published in English. Three independent reviewers will assess publications for eligibility. Data will be extracted on definitions, conceptualizations, and training programs of leadership and followership. Through descriptive and thematic analysis, the review will map the landscape of leadership and followership, and provide insights into related competencies necessary for effective IPC in primary care for patients with chronic illness.

Near-Infrared Fluorescent Probe for the In Situ Visualization of Oxidative Stress in the Brains of Neuroinflammatory and Schizophrenic Mice.

Schizophrenia is a common mental disorder with unclear mechanisms. Oxidative stress and neuroinflammation play important roles in the pathological process of schizophrenia. Superoxide anion (O2•-) is an important oxidative stress biomarker in vivo. However, due to the existence of the blood-brain barrier (BBB), few near-infrared (NIR) fluorescent probes have been used for the sensing and detection of O2•- in the brain. With this research, we developed the first near-infrared fluorescent probe (named CT-CF3) for noninvasive detection of endogenous O2•- in the brain of mice. Enabling fluorescence monitoring of the dynamic changes in O2•- flux due to the prolonged activation of microglia in neuroinflamed and schizophrenic (SZ) mice brains, thereby providing direct evidence for the relationship between oxidative stress, neuroinflammation, and schizophrenia. Furthermore, we confirmed the O2•- burst in the brains of first-episode schizophrenic mice and assessed the effect of two atypical antipsychotic drugs (risperidone and olanzapine) on redox homeostasis.

Selenite-Catalyzed Reaction between Benzoquinone and Acetylacetone Deciphered the Enhanced Inhibition on Microcystis aeruginosa Growth.

The coexistence of selenite (Se(IV)) and acetylacetone (AA) generated a synergistic effect on the growth inhibition of a bloom-forming cyanobacterium, Microcystis aeruginosa. The mechanism behind this phenomenon is of great significance in the control of harmful algal blooms. To elucidate the role of Se(IV) in this effect, the reactions in ternary solutions composed of Se(IV), AA (or two other similar hydrogen donors), and quinones, especially benzoquinone (BQ), were investigated. The transformation kinetic results demonstrate that Se(IV) played a catalytic role in the reactions between AA (or ascorbic acid) and quinones. By comparison with five other oxyanions (sulfite, sulfate, nitrite, nitrate, and phosphate) and two AA derivatives, the formation of an AA-Se(IV) complexation intermediate was confirmed as a key step in the accelerated reactions between BQ and AA. To our knowledge, this is the first report on Se(IV) as a catalyst for quinone-involved reactions. Since both quinones and Se are essential in cells and there are many other chemicals of similar electron-donating properties to that of AA, the finding here shed light on the regulation of electron transport chains in a variety of processes, especially the redox balances that are tuned by quinones and glutathione.

A multi-center cross-sectional study on identification of influencing factors of medical students' emotional engagement in China.

BACKGROUND: Studies exploring influencing factors of emotional engagement among medical students are scarce. Thus, we aimed to identify influencing factors of medical students' emotional engagement. METHODS: We carried out a multi-center cross-sectional study among 10,901 medical students from 11 universities in China. The Chinese version of Utrecht Work Engagement Scale-Student version (UWES-S) was used to evaluate emotional engagement level of medical students. The predictors related to engagement level were determined by the logistic regression analysis. Furthermore, we constructed a nomogram to predict emotional engagement level of medical students. RESULTS: A total of 10,576 sample were included in this study. The mean emotional engagement score was 74.61(± 16.21). In the multivariate logistic regression model, we found that males showed higher engagement level compared with females [odds ratio (OR) (95% confidence interval (CI)): 1.263 (1.147, 1.392), P < 0.001]. Medical students from the second batches of medical universities had higher engagement level and from "Project 985" universities had lower engagement level compared with 211 project universities [OR (95%CI): 1.376 (1.093, 1.733), P = 0.007; OR (95%CI): 0.682 (0.535, 0.868), P = 0.002]. Medical students in grade 4 and grade 2 presented lower engagement level compared with in grade 1 [OR (95%CI): 0.860 (0.752, 0.983), P = 0.027; OR (95%CI): 0.861 (0.757, 0.980), P = 0.023]. Medical students lived in provincial capital cities had higher engagement level compared with in country [OR (95%CI): 1.176 (1.022, 1.354), P = 0.024]. Compared with eight-year emotional duration, medical students in other emotional duration (three-year and four-year) had lower engagement level [OR (95%CI): 0.762 (0.628, 0.924), P = 0.006]. Medical students' engagement level increased with increases of grade point average and interest in studying medicine. Medical students learned by converging style showed lower engagement level [OR (95%CI): 0.827 (0.722, 0.946), P = 0.006] compared with accommodating style. The model showed good discriminative ability (area under curve = 0.778), calibrating ability and clinical utility. CONCLUSIONS: We identified influencing factors of medical students' emotional engagement and developed a nomogram to predict medical students' emotional engagement level, providing reference and convenience for educators to assess and improve emotional engagement level of medical students. It is crucial for educators to pay more attention to emotional engagement of medical students and adopt effective strategies to improve their engagement level.

Si-Rhodamine Derivatives for Brain Fluorescence Imaging and Monitoring of H2S in the Brain of Schizophrenic Mice before and after Treatment.

Schizophrenia is a common type of serious mental illness with an unclear etiology. Recently, the excessive production of hydrogen sulfide in the brain has been considered to be one of the pathophysiological bases of schizophrenia. However, due to the existence of the blood-brain barrier (BBB), almost no fluorescent probe has been successfully used for the sensing and detection of H2S in the brain. Herein, we designed and synthesized a series of near-infrared fluorescent probes SiR-Bs based on a hemicyanine and Si-rhodamine structure. Among them, Mindo-SiR presented a good penetration ability of the BBB, a high brain uptake (transport: 4.95% ID/g at 5 min), and good response to H2S in vitro and in vivo. For the first time, a fluorescent probe was used to image the changes of H2S in the brains of schizophrenic (SZ) mouse models, and it was successfully proven that there was an abnormally high level of H2S in the brains of SZ mice. Moreover, the therapeutic effect of risperidone for the treatment of SZ could be evaluated by the changes of SiR-Bs' fluorescence imaging.

Quercetin induces autophagy-associated death in HL-60 cells through CaMKKß/AMPK/mTOR signal pathway.

Acute myeloid leukemia (AML) is one of the most common malignancies of the hematopoietic progenitor cell in adults. Quercetin has gained recognition over the years because of its anti-cancer effect with minimal toxicity. Herein, we aim to investigate the anti-leukemia mechanism of quercetin and to decipher the signaling pathway of quercetin in HL-60 leukemic cells. We observed that quercetin induces apoptosis and autophagic cell death, in which both pathways play an important role in suppressing the viability of leukemia cells. Phosphorylated AMPK (p-AMPK) protein expressions are lower in primary AML cells, HL-60 cells, KG-1 and THP-1 cells than in peripheral blood monocular cells. After quercetin treatment, the expression of p-AMPK is increased while the expression of p-mTOR is decreased in a dose-dependent manner. Mechanistically, compound C, an AMPK phosphorylation inhibitor, upregulates the phosphorylation of mTOR and inhibits autophagy and apoptosis in quercetin-induced HL-60 cells, while silencing of CaMKKß inhibits the quercetin-induced phosphorylation of AMPK, resulting in increased mTOR phosphorylation. Furthermore, silencing of CaMKKß inhibits the autophagy in HL-60 cells. Taken together, our data delineate that quercetin plays its anti-leukemia role by inhibiting cell viability and inducing apoptosis and autophagy in leukemia cells. Quercetin inhibits the phosphorylation of mTOR by regulating the activity of AMPK, thus playing a role in the regulation of autophagy and apoptosis. CaMKKß is a potential upstream molecule for AMPK/mTOR signaling pathway, through which quercetin induces autophagy in HL-60 cells.

Recent Progress of Surface Modified Nanomaterials for Scavenging Reactive Oxygen Species in Organism.

Reactive oxygen species (ROS) are essential for normal physiological processes and play important roles in signal transduction, immunity, and tissue homeostasis. However, excess ROS may have a negative effect on the normal cells leading to various diseases. Nanomaterials are an attractive therapeutic alternative of antioxidants and possess an intrinsic ability to scavenge ROS. Surface modification for nanomaterials is a critical strategy to improve their comprehensive performances. Herein, we review the different surface modified strategies for nanomaterials to scavenge ROS and their inherent antioxidant capability, mechanisms of action, and biological applications. At last, the primary challenges and future perspectives in this emerging research frontier have also been highlighted. It is believed that this review paper will offer a top understanding and guidance on engineering future high-performance surface modified ROS scavenging nanomaterials for wide biomedical applications.

An all-in-one approach for synthesis and functionalization of nano colloidal gold with acetylacetone.

Controllable synthesis, proper dispersion, and feasible functionalization are crucial requirements for the application of nanomaterials in many scenarios. Here, we report an all-in-one approach for the synthesis and functionalization of gold nanoparticles (AuNPs) with the simplestß-diketone, acetylacetone (AcAc). With this approach, the particle size of the resultant AuNPs was tunable by simply adjusting the light intensity or AcAc dosage. Moreover, owing to the capping role of AcAc, the resultant AuNPs could be stably dispersed in water for a year without obvious change in morphology and photochemical property. Formation of ligand to metal charge transfer complexes was found to play an important role in the redox conversion of Au with AcAc. Meanwhile, the moderate complexation ability enables the surface AcAc on the AuNPs to undergo ligand exchange reactions (LER). With the aid of Ag+, the AuNPs underwent LER with glutathione and exhibited enhanced photoluminescence (PL) with a maximum of 22-fold increase in PL intensity. The PL response was linear to the concentration of glutathione in the range of 0-500µM. Such a LER makes the obtained AuNPs being good imaging probes. To the best of our knowledge, this is the first work on illustrating the roles of AcAc as a multifunctional ligand in fabrication of NPs, which sheds new light on the surface modulation in synthesis of nanomaterials.

UV-Induced Redox Conversion of Tellurite by Biacetyl.

Tellurium (Te) is a rare element of great value, but it exists mainly in the toxic form of tellurite (TeIV) in water. Effective approaches that are able to reduce the toxicity and recover Te from contaminated water are highly needed. Here, we developed a simple but effective way to reduce toxic TeIV to widely applicable elemental Te0. With the combination of ultraviolet (UV) and biacetyl (BD), the oxidation state of Te could be feasibly changed from IV to 0 or VI. The consumption of dissolved oxygen (DO) was a key factor in the redox conversion of TeIV. Under UV irradiation, BD was first cleaved to acetyl radicals, which could then combine with water molecules to form more reductive diol radicals or combine with DO to form strongly oxidative peroxide radicals. Even without deoxygenation, the UV/BD system could rapidly change from being oxidative to being reductive because of the fast depletion of DO. Owing to the high quantum yield of the acetyl radical, the reduction efficiency of the UV/BD system was about 1 order of magnitude higher than that of UV/sulfite and was more efficient than the commonly used biological methods. This work provides a proof of concept for the reduction of tellurite, which could have relevant implications for water treatment and resource recovery applications.

Quantitative structure-activity relationship in the photodegradation of azo dyes.

The photolysis characteristics of azo dyes are critically important in environmental pollution control, dye-sensitized solar cells, and dyeing-related industries. However, there is still lack of quantitative relationship between the structures of azo dyes and their photolysis characteristics. To address this issue, the photolysis of 22 azo dyes were conducted side by side at three pH (4.0, 6.0, 9.0). The obtained pseudo-first order photodegradation rate constants (k1) were processed with meta-analysis. Statistically, the hydrazone tautomer had a smaller excitation energy and was easier to undergo photolysis than the azo tautomer. The ortho-substituted sulfonate groups had an obvious protective effect on the photostability of azo dyes. The softness (s), the most positive and negative partial charge on a carbon atom (qC+, qC-) were found to be crucial descriptors in the establishment of QSAR models for the photostability of azo dyes. The QSAR model at pH 9.0 was robust for predicting the photostability of azo dyes under UV irradiation. N2-purging experiments and quantum chemical computation verified that the cleavage of azo bond was not a result of direct photolysis but was caused by the attack of photoinduced reactive oxygen species. The results here are helpful for the design of more stable azo dyes or the selection of suitable approaches for the treatment of dye-contaminated water bodies.

Mesenchymal stem cells improve platelet counts in mice with immune thrombocytopenia.

Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. The breakdown of immune tolerance (regulatory T [Treg] cells and suppressor cytokines) plays an important role in ITP pathophysiology, especially in refractory ITP. Bone marrow-derived mesenchymal stem cells (BM-MSCs) show immunomodulatory properties and have been extensively utilized for autoimmune diseases. However, it has not been fully elucidated how BM-MSCs affect ITP. In this study, we explore the therapeutic mechanism of BM-MSCs on ITP in mice. Dose-escalation passive ITP mice were inducted by injection of MWReg30. BALB/c mice were randomly divided into two groups: ITP with BM-MSC transplantation and ITP controls. The serum levels of cytokines (interleukin 10 [IL-10] and transforming growth factor-ß1 [TGF-ß1]) were examined by enzyme-linked immunosorbent assays. The frequency of Treg cells in both peripheral blood and spleen mononuclear cells was analyzed by flow cytometry, and the forkhead box P3 (Foxp3) messenger RNA (mRNA) level was measured by real-time polymerase chain reaction. After BM-MSC treatment, the platelet (PLT) counts were significantly elevated. Meanwhile, cytokines (TGF-ß1 and IL-10), the ratios of Treg cells, and the Foxp3 mRNA expression level were significantly higher in the BM-MSC group. Our results show that BM-MSCs can improve PLT counts mainly by secreting suppressive cytokines and upregulating Tregs, which may provide new therapeutic potential for human ITP.

Enhanced Photooxidation of Hydroquinone by Acetylacetone, a Novel Photosensitizer and Electron Shuttle.

Quinones are important electron shuttles as well as micropollutants in the nature. Acetylacetone (AA) is a newly recognized electron shuttle in aqueous media exposed to UV irradiation. Herein, we studied the interactions between AA and hydroquinone (QH2) under steady-state and transient photochemical conditions to clarify the possible reactions and consequences if QH2 and AA coexist in a solution. Steady-state experimental results demonstrate that the interactions between AA and QH2 were strongly affected by dissolved oxygen. In O2-rich solutions, the phototransformation of QH2 was AA-independent. Both QH2 and AA utilize O2 as the electron acceptor, but in O2-insufficient solutions, AA became an important electron acceptor for the oxidation of QH2. In all cases, the coexistence of AA increased the phototransformation of QH2, whereas the decomposition of AA in O2-saturated and oversaturated solutions was inhibited by the presence of QH2. The underlying mechanisms were investigated by a combination of laser flash photolysis (LFP) and reduction potential analysis. The LFP results show that the excited AA serves as a better electron shuttle than QH2. As a consequence, AA might regulate the redox cycling of quinones, leading to significant effects on many processes, ranging from photosynthesis and respiration to photodegradation.

Nonnegligible Generation of Hydroxyl Radicals from UVC Photolysis of Aqueous Nitrous Oxide.

Nitrous oxide (N2O) is widely used in radiation-chemistry and photochemistry as a scavenger to convert a hydrated electron ( eaq-) into a hydroxyl radical (·OH). However, few investigations pay attention to the photochemistry of dissolved N2O itself. The effects of purged N2O on photochemical processes are unclear and neglected. In the present work, the effects of N2O on the hydroxylation of terephthalic acid (TPA) were investigated with both medium-pressure and low-pressure mercury lamps as the light sources. Under short-wavelength UV (200-300 nm) irradiation, N2O accelerated the decay of TPA and the formation of 2-hydroxylterephthalic acid (hTPA). The effective quantum yield of ·OH from the photolysis of dissolved N2O at 254 nm was determined as 1.15-1.63, which was far larger than those of NO3- (0.09) and NO2- (0.046). On the basis of the kinetic analysis in N2 and N2O purged solutions, isotope fractionation with heavy oxygen water, and ·OH scavenging experiments with tert-butyl alcohol, the contribution of the ·OH radicals generated from the photolysis of N2O to the formation of hTPA (61.7%) was determined to be 1 order of magnitude higher than that from the converted eaq- (6.5%). These results demonstrate that using N2O and ·OH probes to quantify photogenerated eaq- in UVC irradiation might lead to false results. The work here is helpful for the proper design of scavenging and probing experiments by the combination of N2O and ·OH probes.

Redox Conversion of Arsenite and Nitrate in the UV/Quinone Systems.

Whether superoxide radical anion (O2•-) was a key reactive species in the oxidation of arsenite (As(III)) in photochemical processes has long been a controversial issue. With hydroquinone (BQH2) and 1,4-benzoquinone (BQ) as redox mediators, the photochemical oxidation of As(III) and reduction of nitrate (NO3-) was carefully investigated. O2•-, singlet oxygen (1O2), H2O2, and semiquinone radical (BQH•) were all possible reactive species in the irradiated system. However, since the formation of As(IV) is a necessary step in the oxidation of As(III), taking the standard reduction potentials into account, the reactions between the above species and As(III) were thermodynamically unfavorable. On the basis of radical scavenging experiments, hydroxyl radical (•OH) was proved as the key species that led to the oxidation of As(III) in the UV/BQH2 system. It should be noted that the •OH radicals were generated from the photolysis of H2O2, which came from the disproportionation of O2•- and the reaction of O2•- with BQH2. Both the photoejected eaq- from 1(BQH2)* and the direct electron transfer with 3(BQH2)* contributed to the reduction of NO3- in the UV/BQH2 process. No synergistic effect was observed in the redox conversion of As(III) and NO3-, further demonstrating that the role of BQH• was negligible in the studied systems. The results here are helpful for a better understanding of the photochemical behaviors of quinones in the aquatic environment.

Methylation-associated silencing of miR-495 inhibit the migration and invasion of human gastric cancer cells by directly targeting PRL-3.

Phosphatase of regenerating liver-3 (PRL-3) is believed to be associated with cell motility, invasion, and metastasis. Our previous work found that PRL-3 is highly overexpressed in gastric cancer (GC) tissue with peritoneal metastasis and directly involved in the pathogenesis of GC peritoneal metastasis. Moreover, we further found that the down-regulation of endogenous miR-495 expression plays a causative role in over expression of PRL-3 in GC peritoneal metastasis. However, the molecular regulation mechanisms by which endogenous miR-495 expression is down-regulated and PRL-3 promotes GC peritoneal metastasis remain to be clearly elucidated. Some studies have shown that the promoter methylation is closely related to the miRNA gene expression. Therefore, in present study, based on our previous findings, we will analysis whether DNA methylation is a major cause of the down-expression of endogenous miR-495, which results in PRL-3 overexpression in GC peritoneal metastasis. Methylation specific PCR (MSP) and sodium bisulfite sequencing method (BSP) detected miR-495 gene promoter methylation status. We treated GC cell lines with 5-Aza-2'-deoxycytidine (5-Aza-dC) to make the gene promoter methylation inactivation. By treating with 5-Aza-dC the migration and invasion of GC cells were significantly inhibited. And the miR-495 was overexpressing, corresponds to the mRNA and protein levels of PRL-3 were reduced, the ability of invasion and metastasis was inhibited. This study suggest that miR-495 have tumor suppressor properties and are partially silenced by DNA hypermethylation in GC, will provide new strategies for prevention and treatment of GC peritoneal metastasis.

Unravelling structural features of small molecules for photochemical transformation of environmental contaminants.

Small molecules, including natural metabolites, organic matter decomposition products, and engineered oxidation byproducts, are widespread in aquatic environment. However, the limited understanding of the photochemical interactions of these small molecules with water pollutants hampers the development of effective environmental protection strategies. This study explores the structural features governing the photochemical transformation of toxic oxyanions by α- and ß-dicarbonyl compounds. By integrating experimental observations with quantum chemical calculations, a robust correlation network was constructed. The correlation network reveals that the reactivity of small organic molecules with oxyanions could be quantitively predicted by their intrinsic properties, such as electronic transition energy, bond dissociation energy, molecular softness, molecular orbital gap, atomic charge, and molecular surface local ionization energy. This network maps the relationship between the molecular architecture of chemicals and their photochemical behaviors. This perspective offers fresh insights into the photochemical behaviors of small molecules in diverse environmental and chemical contexts and are helpful for developing advanced water treatment strategies toward a sustainable future.