An ultra-efficient pretreatment method adopted LPUV/CoFe2O4/PMS-based photolysis for accurate detection of Cd(II) and Pb(II) in water via SWASV.

Dissolved organic matter (DOM) is a widely occurring substance in rivers that can strongly complex with heavy metal ions (HMIs), severely interfering with the electrochemical signal of anodic stripping voltammetry (ASV) and reducing the detection accuracy of HMIs in water. In this study, we investigated a novel advanced oxidation process (AOP) that involves the activation of peroxymonosulfate (PMS) using low-pressure ultraviolet (LPUV) radiation and CoFe2O4 photocatalysis. This novel AOP was used for the first time as an effective pretreatment method to break or weaken the complexation between HMIs and DOM, thereby restoring the electrochemical signals of HMIs. The key parameters, including the PMS concentration, CoFe2O4 concentration, and photolysis time, were optimized to be 6 mg/L, 12 mg/L, and 30 s for eliminating DOM interference during the electrochemical analysis of HMIs via LPUV/CoFe2O4-based photolysis. Investigations of the microstructure, surface morphology, specific surface area, and pore volume of CoFe2O4 were conducted to reveal the exceptional signal recovery capability of LPUV/CoFe2O4/PMS-based photolysis in mitigating interference from DOM during HMIs analysis. The PMS activation mechanism, which is critical to the signal recovery process, was elucidated by analyzing the reactive oxygen species (ROS) and the surface elemental composition of CoFe2O4. Additionally, the degradation and transformation behavior of humus-HMIs complexes were analyzed to study the mechanism of ASV signal recovery further. Notably, the detection results of HMIs in actual water samples obtained using the proposed pretreatment method were compared with those obtained from ICP-MS, yielding an RMSE less than 0.04 µg/L, which indicated the satisfactory performance of the proposed pretreatment method for the ASV detection of HMIs in complex actual samples.

ZnO/g-C3N4 photocatalyst activated by low-pressure ultraviolet for restoring the SWASV signals: A fast pretreatment method for electrochemically detecting Cd2+ and Pb2+ in soil extracts.

Soil organic matter (SOM) significantly impacts the detection accuracy of Cd2+ and Pb2+ using square wave anodic stripping voltammetry (SWASV) due to the complexation of SOM to heavy metal ions (HMIs), thereby attenuating SWASV signals. This study explored an effective pretreatment method that combined low-pressure ultraviolet (LPUV) photolysis with the ZnO/g-C3N4 photocatalyst, activating the photocatalyst to generate highly oxidative •OH radicals and O2•- radicals, which effectively disrupted this complexation, consequently restoring the electroactivity of HMIs and achieving high-fidelity SWASV signals. The parameters of the LPUV-ZnO/g-C3N4 photocatalytic system were meticulously optimized, including the pH of photolysis, duration of photolysis, g-C3N4 mass fraction, and concentration of the photocatalyst. Furthermore, the ZnO/g-C3N4 photocatalyst was thoroughly characterized, with an in-depth investigation on the synergistic interaction between ZnO and g-C3N4 and the mechanisms contributing to the restoration of SWASV signals. This synergistic interaction effectively separated charge carriers and reduced charge transfer resistance, enabling photogenerated electrons (e-) from the conduction band of g-C3N4 to be quickly transferred to the conduction band of ZnO, preventing the recombination of e- and hole (h+) and generating more radicals to disrupt complexation and restore the SWASV signals. Finally, the analysis of HMIs in real soil extracts using the proposed pretreatment method demonstrated high detection accuracy of 94.9% for Cd2+ and 99.8% for Pb2+, which validated the feasibility and effectiveness of the proposed method in environmental applications.

Analysis of the current situation and factors influencing bullying in junior high schools in backward areas of Western, China & A case study of Qingyang City in Gasu.

BACKGROUND: Qingyang is located in the northwest of China. By analyzing the current situation and risk factors of bullying in junior high schools in Qingyang City, and identify relevant data for formulating prevention and control measures of bullying in western backward areas. METHODS: Qingyang City is divided into four regions based on economic level and population quality. One junior high school is randomly selected from each region, a total of 1200 students from 4 junior high schools of different levels in Qingyang City were randomly selected, and the "Questionnaire on Middle School Students' School bullying" was administered between December 2021 and February 2022. RESULTS: The reporting rate of bullying in junior high schools in Qingyang was 47.35%. The incidence of campus bullying among urban-rural integration junior high schools, senior students, and male students is higher than that of municipal -level junior high schools, junior students, and female students (P< 0.05). The results of binary logistic regression showed that the second grade of junior high school (OR = 1.39,95% CI: 1.022-1.894), poor student performance (OR = 1.744,95% CI: 1.09-2.743), external dissatisfaction (OR = 2.09,95% CI: 1.177-3.427), mother working in an enterprise (OR = 1.623,95% CI: 1.074-2.453), and urban-rural integration middle school (OR = 3.631,95% CI: 2.547-5.177) were factors affecting bullying in junior high school campus. CONCLUSION: The reporting rate of bullying in junior high schools in Qingyang City was relatively high, mostly occurring in places lacking supervision and after-school hours. TRIAL REGISTRATION: Not applicable.

Small molecule drug discovery for glioblastoma treatment based on bioinformatics and cheminformatics approaches.

Background: Glioblastoma (GBM) is a common and highly aggressive brain tumor with a poor prognosis for patients. It is urgently needed to identify potential small molecule drugs that specifically target key genes associated with GBM development and prognosis. Methods: Differentially expressed genes (DEGs) between GBM and normal tissues were obtained by data mining the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Gene function annotation was performed to investigate the potential functions of the DEGs. A protein-protein interaction (PPI) network was constructed to explore hub genes associated with GBM. Bioinformatics analysis was used to screen the potential therapeutic and prognostic genes. Finally, potential small molecule drugs were predicted using the DGIdb database and verified using chemical informatics methods including absorption, distribution, metabolism, excretion, toxicity (ADMET), and molecular docking studies. Results: A total of 429 DEGs were identified, of which 19 hub genes were obtained through PPI analysis. The hub genes were confirmed as potential therapeutic targets by functional enrichment and mRNA expression. Survival analysis and protein expression confirmed centromere protein A (CENPA) as a prognostic target in GBM. Four small molecule drugs were predicted for the treatment of GBM. Conclusion: Our study suggests some promising potential therapeutic targets and small molecule drugs for the treatment of GBM, providing new ideas for further research and targeted drug development.

Integrated bioinformatics analysis and network pharmacology to explore the potential mechanism of Patrinia heterophylla Bunge against acute promyelocytic leukemia.

INTRODUCTION: Current treatment with arsenic trioxide and all-trans retinoic acid has greatly improved the therapeutic efficacy and prognosis of acute promyelocytic leukemia (APL), but may cause numerous adverse effects. Patrinia heterophylla Bunge (PHEB), commonly known as "Mu-Tou-Hui" in China, is effective in treating leukemia. However, no studies have reported the use of PHEB for APL treatment. In this study, we aimed to investigate the potential anticancer mechanism of PHEB against APL. METHODS: Public databases were used to search for bioactive compounds in PHEB, their potential targets, differentially expressed genes associated with APL, and therapeutic targets for APL. The core targets and signaling pathways of PHEB against APL were identified by the protein-protein interaction network, Kaplan-Meier curves, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and compound-target-pathway network analysis. Molecular docking was performed to predict the binding activity between the most active compounds and the key targets. RESULTS: Quercetin and 2 other active components of PHEB may exert anti-APL effects through proteoglycans in cancer, estrogen signaling, and acute myeloid leukemia pathways. We also identified 6 core targets of the bioactive compounds of PHEB, including protein tyrosine phosphatase receptor type C, proto-oncogene tyrosine-protein kinase Src, mitogen-activated protein kinase phosphatase 3 (MAPK3), matrix metalloproteinase-9, vascular endothelial growth factor receptor-2, and myeloperoxidase, most of which were validated to improve the 5-year survival of patients. Molecular docking results showed that the active compound bound well to key targets. CONCLUSION: The results not only predict the active ingredients and potential molecular mechanisms of PHEB against APL, but also help to guide further investigation into the anti-APL application of PHEB.

An efficient pretreatment method based on AgNPs-doped SnO2 photocatalyst for the accurate detection of heavy metals in organic-rich water samples.

Humic acid (HA), the primary composition of natural organic matter (NOM) widely distributed in water and soil, can complex with heavy metal ions (HMIs), i.e., Cd(II) and Pb(II) in this study, which deters the accurate detection of HMIs using square wave anodic stripping voltammetry (SWASV). Hence, in this study, an efficient pretreatment method was proposed to restore the electrochemical signal of Cd(II) and Pb(II) by breaking the complexation based on AgNPs-doped SnO2 photocatalyst combined with LP/UV irradiation. Optimization of the key parameters for electrochemical signal restoration including pH for photolysis, AgNPs doping rate, photocatalyst dosage and photolysis time were performed to further elevating the accuracy in the proposed pretreatment method over 96.9% for Cd(II) and Pb(II) in 15 min. The effect of different HA concentrations on SWASV signal of Cd(II) and Pb(II) was also investigated adopting the optimal parameters. Then, the UV-vis absorption spectra, crystal structure, and the morphology of AgNPs-doped SnO2 photocatalyst were investigated to excavate the reasons behind the most excellent AgNPs doping rate to SnO2 in signal restoration. Moreover, the behavior of HA degradation and transformation under LP/UV irradiation was studied to investigate the mechanism of electrochemical signal restoration. Finally, the feasibility of the proposed method was testified by comparing detection results with ICP-MS results using real water samples extracted from aquaculture water.

Study on adsorption of ammonia nitrogen by sodium-modified kaolin at calcination temperature.

Natural kaolin (NK) is not used as a material for removal of ammonia nitrogen in wastewater because of its low ammonia adsorption capacity. In this study, sodium-modified kaolin adsorbent (NaCK) with high ammonia nitrogen adsorption capacity was prepared by NaOH modification of calcined NK, which was developed to address this problem. The adsorption properties were evaluated by batch static adsorption test. The results showed that when the initial concentration of ammonia nitrogen was 10 mg/L, pH = 8, and dosage of adsorbent was 1 g/L, the adsorption capacity of NaCK-600 for ammonia nitrogen was the best, reaching 6.23 mg/g, which was 34.6 times higher than that of NK (0.18 mg/g). Batch static adsorption test combined with adsorption kinetics, adsorption isothermal, and characteristic data showed that NaCK prepared at different temperatures had different adsorption mechanisms. Batch static adsorption test data of NaCK-600 was in good agreement with the pseudo-second-order model and Langmuir model, and the main mechanism of its adsorption of ammonia nitrogen was the ion exchange of NH4+ and Na+ in NaCK. After the third cycle, the removal rate of NaCK-600 was still up to 76.44%, which indicates that NaCK-600 has considerable potential for removal of ammonia nitrogen in wastewater and provides a new way for the application of kaolin in removal of ammonia nitrogen.

Studying noncovalent or covalent bond problem between smoothened and cholesterol by molecular dynamics simulation and Markov state model.

Smoothened (SMO) is an attractive therapeutic target for the treatment and prevention of several malignant tumors of the nervous system. The crystal structure of SMO shows cholesterol interacts with residue Asp95 via the noncovalent bond. However, some studies indicate that cholesterol covalently binds to residue Asp95 of SMO. To study these contradictory results, we performed molecular dynamics (MD) simulations and Markov state model (MSM) on SMO in complex with noncovalent-bound and covalent-bound cholesterol. The MD simulated results showed that the noncovalent-bound cholesterol was extremely unstable around the position of residue Asp95 of SMO, while the covalent-bound cholesterol could keep the stable connection with residue Asp95 of SMO. The free energy landscape showed that noncovalent-bound cholesterol had more deep energy wells than covalent-bound cholesterol when it dynamically interacted with the extracellular domain of SMO crystal structure. The MSM results showed the noncovalent-bound cholesterol had more dynamic configuration transformation pathways than the covalent-bound cholesterol. These results theoretically revealed cholesterol should have a covalent bond with residue Asp95 if cholesterol could be stable in the near position of residue Asp95 of SMO. Our studies not only elucidate the covalent binding contradictory issue between cholesterol and residue Asp95 of SMO, but also supply helpful information for antagonists design of SMO.

Two birds with one stone: A highly sensitive near-infrared BODIPY-based fluorescent probe for the simultaneous detection of Fe2+ and H+ in vivo.

Ferrous ion (Fe2+) plays an essential role in many physiological and pathological processes, and its cellular metabolism is closely related to acidic pH. However, the lack of multifunctional Fe2+ probes has hindered the further study of Fe2+ in vivo. Herein, we report a dual-responsive near-infrared (NIR) fluorescent probe BODIPY-Fe for the simultaneous of Fe2+ and H+ in vivo by harnessing the N-oxide strategy and photoinduced electron transfer (PeT) mechanism. BODIPY-Fe exhibited NIR fluorescence at 671 nm, rapid response to Fe2+ within 90 s, and high sensitivity of low LOD of 292 nM towards Fe2+. Moreover, BODIPY-Fe could sensitively and selectively detect Fe2+ and H+ in the lysosomes of living cells simultaneously. Notably, BODIPY-Fe was able to noninvasively visualize Fe2+ and H+ in vivo, showing "ON-OFF-ON" NIR fluorescence signal changes. This work demonstrates that BODIPY-Fe has great potential to promote the simultaneous imaging of Fe2+ and H+ in biological systems.

Conformation Transition of Intracellular Part of Glucagon Receptor in Complex With Agonist Glucagon by Conventional and Accelerated Molecular Dynamics Simulations.

The inactive conformations of glucagon receptor (GCGR) are widely reported by crystal structures that support the precision structure for drug discovery of type 2 diabetes. The previous study shows that the intracellular part is open in the glucagon-bound GCGR (glu-GCGR) and closed in the apo-GCGR by accelerated molecular dynamics (aMD) simulations. However, the crystal structure of GCGR in complex with partial agonist shows that the intracellular part is closed in the inactive conformation. To understand the differences between the studies of aMD simulations and crystal structure, the 2,500 ns conventional molecular dynamics (cMD) simulations are performed on the simulated model of glu-GCGR. The result shows that the transmembrane helices (TMH) 6 of glu-GCGR is outward ~4 Å to drive the intracellular part of glu-GCGR open until ~390 ns cMD simulations. The (TMH) 6 of glu-GCGR becomes closed after ~490 ns cMD simulations, which are consistent with the crystal structure of GCGR in complex with the partial agonist. To further elucidate the activation mechanism of GCGR deeply, the simulated models of glu-GCGR, apo-GCGR, and antagonist-bound GCGR (ant-GCGR) are constructed to perform 10 of parallel 300 ns aMD simulations, respectively. The results show that both of glu-GCGR and apo-GCGR can generate the open conformations of the intracellular part. But the glu-GCGR has the higher percentage of open conformations than apo-GCGR. The ant-GCGR is restricted to generate the open conformations of the intracellular part by antagonist MK-0893. It indicates that the glu-GCGR, apo-GCGR, and ant-GCGR can be distinguished by the aMD simulated method. Free energy landscape shows that the open conformations of the intracellular part of GCGR are in intermediate state. Our results show that aMD simulations enhance the space samplings of open conformations of GCGR via adding extra boost potential. It indicates that the aMD simulations are an effective way for drug discovery of GCGR.

[Prognostic value of cyclin E and its relation to blood vessel invasion in rectal cancer].

OBJECTIVE: To investigate the expression of cyclin E in rectal carcinoma and its prognostic significance. METHODS: Cyclin E expression was examined by Western blotting in tumor tissue samples from 130 potentially resected rectal cancer patients with pathological stages I- III. Blood vessel invasion (BVI) was detected by immunohistochemistry. Multivariate analysis using the COX proportional hazards models was applied to evaluate the independent prognostic tumor markers of rectal cancer. RESULTS: The high expression rate of cyclin E in rectal carcinoma tissue was 23.1%(30/130). Except for a positive correlation with BVI and the gross configuration of tumor, the expression of cyclin E showed no significant relation to other clinicopathological factors. The 5-year disease-specific survival rate of cyclin E high expression group was 29.2%, which was significantly lower as compared to that of cyclin low expression group 70.5% (P<0.05). Multivariate analysis revealed that histology and cyclin E expression were independent prognostic indicators for rectal cancer patients at stages I- III. Compared to those with low expression levels, patients with high cyclin E levels had the hazard ratio (95%CI) for death from rectal cancer for 3.544 (1.528-8.215). In stage I- II, multivariate analysis showed that stronger predictive values of cyclin E expression even were detected. Patients with low cyclin E expression and negative BVI had a significantly better prognosis than those with high cyclin E expression and positive BVI. CONCLUSIONS: The expression of cyclin E is independent prognostic factor in rectal carcinoma at stages I- III. Detecting the expression of cyclin E and/or combined with BVI may help to predict clinical outcome and design further individualized intensive adjuvant treatment.

The association of CYP2D6 *10 polymorphism with breast cancer risk and clinico-pathologic characteristics in Chinese women.

A relatively little is known of whether CYP2D6 *10 (188 C to T) polymorphism mediates susceptibility to breast cancer. In this study the CYP2D6 *10 polymorphism was detected in Chinese women (286 breast cancer patients and 305 healthy women) by a PCR-RFLP assay. We found that women with the 188T/T genotype displayed a slightly increased risk for breast cancer as compared with those with the 188C/C genotype (OR 1.36, CI 0.89-2.1), the association of the 188T/T genotype with breast cancer risk was more pronounced among postmenopausal women (OR 1.49, CI 0.8-2.76), but the association did not reach statistical significance. Furthermore, we found that patients carrying the 188T/T or T/C genotype were more likely to be a positive lymph node status than those with the 188C/C genotype (OR 2.12, CI 1.08-4.18, P = 0.019). Our results suggest that CYP2D6 *10 mutant 188T/T genotype displays a non-significant increased risk for breast cancer. Moreover, patients carrying 188T/T or T/C genotype might exhibit a more aggressive phenotype than those carrying 188C/C genotype, as the observation association of genotype with clinical outcome may be due to chance, therefore, further studies are required to confirm our present findings.