The effects of alfacalcidol combined with calcitonin in the treatment of osteoporosis and its influence on levels of inflammation.

OBJECTIVE: To investigate the effectiveness of Alfacalcidol combined with Calcitonin in the treatment of osteoporosis and its influence on the degree of pain, bone metabolism indexes, bone mineral density and inflammatory factor levels. METHODS: In this retrospective study, 110 patients with osteoporosis treated in The Second Affiliated Hospital of Shandong First Medical University from January 2019 to June 2021 were selected as the study subjects. According to different treatment methods, these patients were divided into an observation group and a control group with 55 cases in each group. Patients from the control group were treated with the alfacalcidol capsules alone, while those from the observation group were treated with the alfacalcidol capsules combined with intramuscular calcitonin injection. Patients in both groups were treated for 6 months continuously. The treatment effect, visual analogue scale (VAS) score and Oswestry disability index (ODI), bone mineral density (BMD), serum markers levels such as calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase-5b (TRACP-5b), insulin-like growth factor (IGF-1), type I procollagen amino terminal propeptide (PINP) and ß-collagen special sequence (ß-Crosslaps), the levels of inflammatory factor including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), quality Life Questionnaire Core 30 (QLQ-C30) scores and incidences of adverse reactions were evaluated and compared between the two groups. RESULTS: The effective rate of patients in the observation group was 90.91%, which was significantly higher than 74.54% in the control group (P<0.05). There was no significant difference in the term of VAS score, ODI score, serum markers levels, bone mineral density, inflammatory levels, QLQ-C30 before treatment between the two groups. Compared with the control group, the post-treatment VAS score, ODI score, the levels of IL-6, TNF-α, TRACP-5b, PINP and ß-Crosslaps in the observation group were obviously lower, while the post-treatment QLQ-C30, bone mineral density, Ca, P, ALP, IGF-1 levels were significantly higher (all P<0.05). No statistical differences were found in the incidences of adverse reactions between the two groups (P>0.05). CONCLUSION: The combination of Alfacalcidol combined with Calcitonin is effective in the treatment of osteoporosis patients, which can effectively improve the levels of bone metabolism indexes and bone mineral density, alleviate the symptoms, enhance the life quality and reduce the levels of inflammation. Therefore, it is worth promoting.

Rapid determination of total flavonoid content, xanthine oxidase inhibitory activities, and antioxidant activity in Prunus mume by near-infrared spectroscopy.

Evaluating the quality of herbal medicine based on the content and activity of its main components is highly beneficial. Developing an eco-friendly determination method has significant application potential. In this study, we propose a new method to simultaneously predict the total flavonoid content (TFC), xanthine oxidase inhibitory (XO) activity, and antioxidant activity (AA) of Prunus mume using near-infrared spectroscopy (NIR). Using the sodium nitrite-aluminum nitrate-sodium hydroxide colorimetric method, uric acid colorimetric method, and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) free radical scavenging activity as reference methods, we analyzed TFC, XO, and AA in 90 P. mume samples collected from different locations in China. The solid samples were subjected to NIR. By employing spectral preprocessing and optimizing spectral bands, we established a rapid prediction model for TFC, XO, and AA using partial least squares regression (PLS). To improve the model's performance and eliminate irrelevant variables, competitive adaptive reweighted sampling (CARS) was used to calculate the pretreated full spectrum. Evaluation model indicators included the root mean square error of cross-validation (RMSECV) and determination coefficient (R2) values. The TFC, XO, and AA model, combining optimal spectral preprocessing and spectral bands, had RMSECV values of 0.139, 0.117, and 0.121, with RCV2 values exceeding 0.92. The root mean square error of prediction (RMSEP) for the TFC, XO, and AA model on the prediction set was 0.301, 0.213, and 0.149, with determination coefficient (RP2) values of 0.915, 0.933, and 0.926. The results showed a strong correlation between NIR with TFC, XO, and AA in P. mume. Therefore, the established model was effective, suitable for the rapid quantification of TFC, XO, and AA. The prediction method is simple and rapid, and can be extended to the study of medicinal plant content and activity.

Fully Integrated Multiplexed Wristwatch for Real-Time Monitoring of Electrolyte Ions in Sweat.

Considerable progress has already been made in sweat sensors based on electrochemical methods to realize real-time monitoring of biomarkers. However, realizing long-term monitoring of multiple targets at the atomic level remains extremely challenging, in terms of designing stable solid contact (SC) interfaces and fully integrating multiple modules for large-scale applications of sweat sensors. Herein, a fully integrated wristwatch was designed using mass-manufactured sensor arrays based on hierarchical multilayer-pore cross-linked N-doped porous carbon coated by reduced graphene oxide (NPCs@rGO-950) microspheres with high hydrophobicity as core SC, and highly selective monitoring simultaneously for K+, Na+, and Ca2+ ions in human sweat was achieved, exhibiting near-Nernst responses almost without forming an interfacial water layer. Combined with computed tomography, solid-solid interface potential diffusion simulation results reveal extremely low interface diffusion potential and high interface capacitance (598 µF), ensuring the excellent potential stability, reversibility, repeatability, and selectivity of sensor arrays. The developed highly integrated-multiplexed wristwatch with multiple modules, including SC, sensor array, microfluidic chip, signal transduction, signal processing, and data visualization, achieved reliable real-time monitoring for K+, Na+, and Ca2+ ion concentrations in sweat. Ingenious material design, scalable sensor fabrication, and electrical integration of multimodule wearables lay the foundation for developing reliable sweat-sensing systems for health monitoring.

Protective effect of resveratrol on nickel-refining fumes-induced inflammatory damage.

Nickel (Ni), a ductile and hard silver-white transition metal, is commonly found in occupational environments and can harm the human body. Since it is a toxic compound, long-term Ni exposure can cause pneumonia, rhinitis, and other types of respiratory inflammatory diseases. Resveratrol (Res) is a plant antitoxin polyphenol, which also has anti-cancer and anti-inflammatory properties. In this report, the toxicity of Ni-refining fumes on the human lung bronchial epithelial (BEAS-2B) cells, as well as the protective effects of Res were investigated in vitro, and the specific mechanism of its anti-inflammatory effect was explained. The experimental observations of this study revealed that Ni-refining fumes induce BEAS-2B cell damage, increase reactive oxygen species (ROS) content, activate NLRP3 (LRR-, NOD-, and pyrin domain-containing 3) inflammasome, and promote the secretion of the cytokine Interleukin (IL)-1ß, leading to cellular inflammation and reducing cell activity. Resveratrol (20 µmol/L) activated sirtuin 1 (SIRT1) in BEAS-2B cells to increase protein and mRNA expression. SIRT1 was observed to inhibit the transcriptional activity of nuclear factor-kappaB (NF-κB), reduced the expression of NLRP3 protein and mRNA, and inhibited NLRP3 inflammation. The level of inflammasome activation and IL-1ß overexpression could reduce the inflammatory damage caused by the Ni-refining fume particles on the BEAS-2B cells and exert anti-inflammatory protective effects. In vivo experiments further confirmed that resveratrol could effectively alleviate the acute inflammatory injuries caused due to exposure to the Ni-refining fume particles in the lung tissues of the Wistar rats, and verified that resveratrol could exert its anti-inflammatory impact through the SIRT1-NF-κB-NLRP3 pathway. These results provide an important theoretical basis for developing novel protective drugs and investigating the mechanism of action for inflammatory injury in occupational populations caused by exposure to nickel and other heavy metals.

Evaluating the causal effect of atherosclerosis on the risk of intervertebral disc degeneration.

Background: Intervertebral disc degeneration (IDD) and atherosclerosis are two common age-related conditions that can cause significant morbidity. While previous studies have suggested an association between the two conditions, the nature of this association remains unclear. Methods: We used Mendelian randomization (MR) to investigate the causal relationship between IDD and atherosclerosis. We identified genetic variants associated with IDD using summary statistics from a large genome-wide association study (GWAS). These variants were then used as instrumental variables to infer causal relationships with atherosclerosis in summary statistics from a separate GWAS. Results: Our MR analysis provided evidence for a causal relationship between IDD and atherosclerosis. We found that the genetic predisposition to atherosclerosis was associated with a higher risk of IDD (odds ratio [OR] = 3.55, 95% confidence interval [CI]: 1.07-11.74, p = 0.04). The IVW estimates were consistent with the observational findings and other robust MR methods. Sensitivity analyses suggested that our findings were robust to potential sources of bias. Conclusions: Our study provides evidence for a causal link between IDD and atherosclerosis, suggesting that interventions targeting atherosclerosis could have potential benefits for reducing the risk of IDD. Further research is needed to explore the underlying mechanisms that link these two conditions and to investigate potential therapeutic interventions.

Highly Accurate Determination of the Total Amount of Pb2+ and Pb(OH)+ in a Natural Water Environment Revealed by Dynamic Simulation and DFT Calculation: Benefit from the Electron Inverse Effect of Pt Nanoclusters over Defective g-C3N4.

Although utilizing nanomaterial-modified electrodes for lead ion detection has achieved great success, most of them are carried out under acidic conditions and ignore the variation of Pb(II) speciation at different pH conditions, leading to the potential inaccuracy of Pb(II) detection in a neutral natural water environment. Thus, designing a novel catalyst with high accuracy for the detection of various forms of the total amount of Pb(II) (Pb2+ and Pb(OH)+) in neutral waters is significant. Herein, Pt nanoclusters (Pt NCs) were elaborately constructed and stabilized on the Co single-atom-doped g-C3N4 with abundant N vacancies (Pt NCs/VN-C3N4), which achieved the ultrasensitive detection (102.16 µM µA-1) of Pb(II) in neutral conditions. The dynamic simulation and theoretical calculations reveal that the parallel deposition of Pb2+ and Pb(OH)+ occurs on the electrode surface modified by Pt NCs/VN-C3N4, and the current peaks of Pb(II) are cocontributed by Pb2+ and Pb(OH)+ species. An "electron inverse" phenomenon in Pt NCs/VN-C3N4 from the VN-C3N4 substrate to Pt NCs endows Pt NCs in an electron-rich state, serving as active centers to promote rapid and efficient reduction for both Pb2+ and Pb(OH)+, facilitating the accurate detection of the total amount of Pb(II) in all forms in the actual water environment.

Predictive potentials of glycosylation-related genes in glioma prognosis and their correlation with immune infiltration.

Glycosylation is currently considered to be an important hallmark of cancer. However, the characterization of glycosylation-related gene sets has not been comprehensively analyzed in glioma, and the relationship between glycosylation-related genes and glioma prognosis has not been elucidated. Here, we firstly found that the glycosylation-related differentially expressed genes in glioma patients were engaged in biological functions related to glioma progression revealed by enrichment analysis. Then seven glycosylation genes (BGN, C1GALT1C1L, GALNT13, SDC1, SERPINA1, SPTBN5 and TUBA1C) associated with glioma prognosis were screened out by consensus clustering, principal component analysis, Lasso regression, and univariate and multivariate Cox regression analysis using the TCGA-GTEx database. A glycosylation-related prognostic signature was developed and validated using CGGA database data with significantly accurate prediction on glioma prognosis, which showed better capacity to predict the prognosis of glioma patients than clinicopathological factors do. GSEA enrichment analysis based on the risk score further revealed that patients in the high-risk group were involved in immune-related pathways such as cytokine signaling, inflammatory responses, and immune regulation, as well as glycan synthesis and metabolic function. Immuno-correlation analysis revealed that a variety of immune cell infiltrations, such as Macrophage, activated dendritic cell, Regulatory T cell (Treg), and Natural killer cell, were increased in the high-risk group. Moreover, functional experiments were performed to evaluate the roles of risk genes in the cell viability and cell number of glioma U87 and U251 cells, which demonstrated that silencing BGN, SDC1, SERPINA1, TUBA1C, C1GALT1C1L and SPTBN5 could inhibit the growth and viability of glioma cells. These findings strengthened the prognostic potentials of our predictive signature in glioma. In conclusion, this prognostic model composed of 7 glycosylation-related genes distinguishes well the high-risk glioma patients, which might potentially serve as caner biomarkers for disease diagnosis and treatment.

Ion-Electron Transduction Layer of the SnS2-MoS2 Heterojunction to Elevate Superior Interface Stability for All-Solid Sodium-Ion Selective Electrode.

The high selectivity and fast ion response of all-solid sodium ion selective electrodes were widely applied in human sweat analysis. However, the potential drift due to insufficient interfacial capacitance leads to the deterioration of its stability and ultimately affects the potential accuracy of ion analysis. Designing a novel ion-electron transduction layer between the electrode and the ion selective membrane is an effective method to stabilize the interfacial potential. Herein, the SnS2-MoS2 heterojunction material was constructed by doping Sn in MoS2 nanosheets and used as the ion electron transduction layers of an all-solid sodium ion selective electrode for the first time, achieving the stable and efficient detection of Na+ ions. The proposed electrode exhibited a Nernst slope of 57.86 mV/dec for the detection of Na+ ions with a detection limit of 10-5.7 M in the activity range of 10-6-10-1 M. Via the electronic interaction at the heterojunction interfaces between SnS2 and MoS2 materials, the micro-nanostructure of the SnS2-MoS2 heterojunction was changed and SnS2-MoS2 as the ion-electron transduction layer acquired excellent capacitance (699 µF) and hydrophobicity (132°), resulting in a long-term potential stability of 1.37 µV/h. It was further proved that the large capacitance and high hydrophobicity of the ion-electron transduction layer are primary reasons for the excellent stability of the all-solid sodium ion selective electrode toward Na+ ions.

Integrated analysis of plasma proteome and cortex single-cell transcriptome reveals the novel biomarkers during cortical aging.

Background: With the increase of age, multiple physiological functions of people begin gradually degenerating. Regardless of natural aging or pathological aging, the decline in cognitive function is one of the most obvious features in the process of brain aging. Brain aging is a key factor for several neuropsychiatric disorders and for most neurodegenerative diseases characterized by onset typically occurring late in life and with worsening of symptoms over time. Therefore, the early prevention and intervention of aging progression are particularly important. Since there is no unified conclusion about the plasma diagnostic biomarkers of brain aging, this paper innovatively employed the combined multi-omics analysis to delineate the plasma markers of brain aging. Methods: In order to search for specific aging markers in plasma during cerebral cortex aging, we used multi-omics analysis to screen out differential genes/proteins by integrating two prefrontal cortex (PFC) single-nucleus transcriptome sequencing (snRNA-seq) datasets and one plasma proteome sequencing datasets. Then plasma samples were collected from 20 young people and 20 elder people to verify the selected differential genes/proteins with ELISA assay. Results: We first integrated snRNA-seq data of the post-mortem human PFC and generated profiles of 65,064 nuclei from 14 subjects across adult (44-58 years), early-aging (69-79 years), and late-aging (85-94 years) stages. Seven major cell types were classified based on established markers, including oligodendrocyte, excitatory neurons, oligodendrocyte progenitor cells, astrocytes, microglia, inhibitory neurons, and endotheliocytes. A total of 93 cell-specific genes were identified to be significantly associated with age. Afterward, plasma proteomics data from 2,925 plasma proteins across 4,263 young adults to nonagenarians (18-95 years old) were combined with the outcomes from snRNA-seq data to obtain 12 differential genes/proteins (GPC5, CA10, DGKB, ST6GALNAC5, DSCAM, IL1RAPL2, TMEM132C, VCAN, APOE, PYH1R, CNTN2, SPOCK3). Finally, we verified the 12 differential genes by ELISA and found that the expression trends of five biomarkers (DSCAM, CNTN2, IL1RAPL2, CA10, GPC5) were correlated with brain aging. Conclusion: Five differentially expressed proteins (DSCAM, CNTN2, IL1RAPL2, CA10, GPC5) can be considered as one of the screening indicators of brain aging, and provide a scientific basis for clinical diagnosis and intervention.

Revealing the solid-solution interface interference behaviors between Cu2+ and As(III) via partial peak area analysis of simulations and experiments.

The mutual interference in the sensing detection of heavy metal ions (HMIs) is considerably serious and complex. Besides, the co-existed ions may change the stripping peak intensity, shape and position of the target ion, which partly makes peak current analysis inaccurate. Herein, a promising approach of partial peak area analysis was proposed firstly to research the mutual interference. The interference between two species on their electrodeposition processes was investigated by simulating different kinetics parameters, including surface coverage, electro-adsorption, -desorption rate constant, etc. It was proved that the partial peak area is sensitive and regular to these interference kinetics parameters, which is favorable for distinctly identifying different interferences. Moreover, the applicability of the partial peak area analysis was verified on the experiments of Cu2+, As(III) interference at four sensing interfaces: glassy carbon electrode, gold electrode, Co3O4, and Fe2O3 nanoparticles modified electrodes. The interference behaviors between Cu2+ and As(III) relying on solid-solution interfaces were revealed and confirmed by physicochemical characterizations and kinetics simulations. This work proposes a new descriptor (partial peak area) to recognize the interference mechanism and provides a meaningful guidance for accurate detection of HMIs in actual water environment.

Bimodal interferences of Pb(II) induced by parallel deposition in Pb(II)-Cu(II) electrochemical detections: Voltammetric signals analysis combined with numerical simulations on transient interfacial phenomena.

The perplexity of double peaks in Pb(II) detections has been a threat to the reliability of Pb(II) electroanalysis results for a long term. For the complexity of electrode interfaces, rare studies were taken on mechanisms of Pb(II) double peaks through interfacial kinetics. In this work, analyses on experimental signals and interfacial simulations were working together to reveal that the generation of Pb(II) double peaks in Pb(II)-Cu(II) systems is the deposition of Pb(II) on Cu deposits occurring in parallel. By applying anode stripping voltammetry and cyclic voltammetry, a parallel deposition reaction was found to influence the shape of Pb(II) peaks, and the existence of the second peak was controlled through the adjustment of experimental conditions. A kinetic model was built to reveal the interference of electroanalysis signals caused by a parallel deposition reaction and simulations based on the model were combined with experiments to illustrate that double peaks of Pb(II) were caused by the parallel deposition on Cu(II) deposits. This work proposes another insight of Pb(II) double peaks from macroscale kinetics and pays more attention on the dynamic procedure of electroanalysis interfaces, which makes the study on environmental electroanalysis interface phenomena more clear and is enlightening to develop efficient electrical methods for pollutant monitoring.

Scutellarin inhibits the glioma cell proliferation by downregulating BIRC5 to promote cell apoptosis.

The expression changes of baculovirus inhibitor of apoptosis repeat-containing protein5 in brain glioma after administration of Scutellarin was detected. To explore the effort of scutellarin on anti-glioma by downregulating BIRC5.The effect of scutellarin on tumour growth and animal survival was detected by administering scutellarin to nude mice subcutaneous tumour formation and SD rats in situ tumour formation models. A significantly different gene BIRC5 was found by using the combination of TCGA databases and network pharmacology. And then qPCR was performed to detect the expression of BIRC5 in glioma tissues, cells and normal brain tissues and glial cells. CCK-8 was used to detect the IC50 of scutellarin on glioma cells. The wound healing assay, flow cytometry and MTT test were used to detect the effect of scutellarin on the apoptosis and proliferation of glioma cells. The expression of BIRC5 in glioma tissues was significantly higher than that in normal brain tissues. Scutellarin can significantly reduce tumour growth and improve animal's survival. After scutellarin was administered, the expression of BIRC5 in U251 cells was significantly reduced. And after same time, apoptosis increased and cell proliferation was inhibited. This original research showed that scutellarin can promote the apoptosis of glioma cells and inhibit the proliferation by downregulating the expression of BIRC5.

Excellent Dielectric Properties and Finite Element Simulation of Al-Epoxy Composites with Constructed Ultrathin Al2O3 Parallel-Plate Microcapacitors.

Metal-polymer dielectric composites show promising potential as embedded capacitors, whereas it remains a great challenge to achieve a high dielectric constant (εr) and low dielectric loss (tan δ) simultaneously. This work demonstrates a strategy for overcoming this challenge. Al nanoparticles with self-passivated ultrathin Al2O3 shells are compacted under the uniaxial pressure (P), and Al-epoxy composites are prepared by curing the liquid epoxy monomer that infiltrates into Al compacts. The contacting regions between adjacent Al nanoparticles are flattened and enlarged during the compacting process, so that the ultrathin Al2O3 parallel-plate microcapacitors are constructed by the insulating Al2O3 shells and conductive Al cores. The composite with P of 100 MPa and Al volume fraction (υAl) of 53.7% exhibits the εr of 189 at 10 kHz, which is much higher than the εr (48-102) of 0-3 type Al-polymer composites with similar υAl and even higher than the highest εr (160) reported in the Al-polymer composite with υAl > 80%. Furthermore, the present composites show low tan δ (<0.03) and good frequency and temperature stability of εr. The finite element simulation proves that the construction and enlargement of ultrathin Al2O3 parallel-plate microcapacitors dramatically increase the electric energy stored in Al2O3 and therefore greatly improve the εr.

Heavy metals in riverine/estuarine sediments from an aquaculture wetland in metropolitan areas, China: Characterization, bioavailability and probabilistic ecological risk.

Aquaculture wetlands, particularly those located within urban areas, are fragile ecosystems due to urban and aquaculture impacts. However, to date, there are no reports on the combined toxicity of heavy metal mixtures in aquatic biota in sediments from aquaculture wetlands in metropolitan areas. Thus, the characterization, bioavailability, and ecological probability risk of heavy metals were studied in the riverine/estuarine sediments of the Rongjiang River in an aquaculture wetland in Chaoshan metropolis, South China. In the study area, the average total concentrations (mg/kg) were 2.38 (Cd), 113.40 (Pb), 88.27 (Cr), 148.25 (Ni), 62.08 (Cu), 125.18 (Zn), 45,636.44 (Fe), and 797.18 (Mn), with the Cd pollution being regarded as extremely serious based on the enrichment factor (EF). There are two main sources of heavy metals in the study area; Ni, Pb, Zn, Fe and Mn are mainly from domestic waste, while Cr, Cd and Cu are possibly associated with industrial production activities. The bioavailability of most heavy metals accounted for more than 20% of the total concentration. The combined toxicity of heavy metal mixtures based on probabilistic risk assessment suggests that the surface sediments of the Rongjiang River and its estuary had a 15.71% probability of toxic effects on aquatic biota.

Distribution, Multi-Index Assessment, and Sources of Heavy Metals in Surface Sediments of Zhelin Bay, a Typical Mariculture Area in Southern China.

The occurrence, multi-index assessment, and sources of heavy metals in surface sediments of Zhelin Bay were investigated. Average heavy metal concentrations (mg/kg) were 81.89 (Cr), 770.76 (Mn), 16.81 (Co), 62.25 (Ni), 96.30 (Cu), 162.04 (Zn), and 73.40 (Pb), with the concentrations of studied seven heavy metals being significantly higher than their corresponding background values. Geo-accumulation index (Igeo) and pollution load index (PLI) were implemented to assess degree of heavy metal contamination. The Igeo and PLI indicated that Cr, Mn, Co, Zn, and Pb were slightly polluted, and Cu and Ni were moderately polluted in the region. Potential ecological risk index (RI) and mean possible effect level (PEL) quotient were conducted to assess ecological risk. The RI and mean PEL quotient demonstrated that surface sediments of Zhelin Bay were slight ecological risks and exhibited a 21% probability of toxicity. Principal component analysis (PCA) combined with the correlation analysis (CA) and hierarchical cluster analysis (HAC) revealed that the heavy metal contamination in Zhelin Bay might originate from three type sources.

The role of post-transcriptional modification on a new tRNAIle(GAU) identified from Ganoderma lucidum in its fragments' cytotoxicity on cancer cells.

Ganoderma lucidum (Ganoderma) is a famous Chinese herbal medicine which has been used clinically for thousands of years in China. Despite numerous studies on triterpenes and polysaccharides, the bioactivity of RNAs abundant in Ganoderma remains unknown. Here, based on LC-MS techniques, dihydrouracil, 5-methyluridine (m5U) and pseudouridine were identified at position 19, 52 and 53 of a new tRNAIle(GAU) which was isolated as the most abundant tRNA species in Ganoderma, and is the first purified tRNA from fungus. Cytotoxic screening of tRNA-half (t-half) and tRNA fragment (tRF) derived from this tRNA, as well as their mimics (t-half or tRF as antisense strand), demonstrated that the double-stranded form, i.e., tRF and t-halve mimics, exhibited stronger cytotoxicity than their single-stranded form, and the cytotoxicity of t-half mimic is significantly stronger than that of tRF mimic. Notably, the cytotoxicity of 3'-t-half mimic is not only much more potent than that of taxol, but also is much more potent than that of ganoderic acids, the major bioactive components in Ganoderma. Furthermore, 3'-t-half mimic_M2 (m5U modified) exhibited significantly stronger cytotoxicity than unmodified 3'-t-half mimic, which is consistent with the computational simulation showing that m5U modification enhances the stability of the tertiary structure of 3'-t-half mimic. Overall, the present study not only indicates t-halves are bioactive components in Ganoderma which should not be neglected, but also reveals an important role of post-transcriptional modification on tRNA in its fragments' cytotoxicity against cancer cells, which benefits the design and development of RNAi drugs from natural resource.

Practical Strategy for Arsenic(III) Electroanalysis without Modifier in Natural Water: Triggered by Iron Group Ions in Solution.

Significant progress has been made in nanomaterial-modified electrodes for highly efficient electroanalysis of arsenic(III) (As(III)). However, the modifiers prepared using some physical methods may easily fall off, and active sites are not uniform, causing the potential instability of the modified electrode. This work first reports a promising practical strategy without any modifiers via utilizing only soluble Fe3+ as a trigger to detect trace-level As(III) in natural water. This method reaches an actual detection limit of 1 ppb on bare glassy carbon electrodes and a sensitivity of 0.296 µA ppb-1 with excellent stability. Kinetic simulations and experimental evidence confirm the codeposition mechanism that Fe3+ is preferentially deposited as Fe0, which are active sites to adsorb As(III) and H+ on the electrode surface. This facilitates the formation of AsH3, which could further react with Fe2+ to produce more As0 and Fe0. Meanwhile, the produced Fe0 can also accelerate the efficient enrichment of As0. Remarkably, the proposed sensing mechanism is a general rule for the electroanalysis of As(III) that is triggered by iron group ions (Fe2+, Fe3+, Co2+, and Ni2+). The interference analysis of coexisting ions (Cu2+, Zn2+, Al3+, Hg2+, Cd2+, Pb2+, SO42-, NO3-, Cl-, and F-) indicates that only Cu2+, Pb2+, and F- showed inhibitory effects on As(III) due to the competition of active sites. Surprisingly, adding iron power effectively eliminates the interference of Cu2+ in natural water, achieving a higher sensitivity for 1-15 ppb As(III) (0.487 µA ppb-1). This study provides effective solutions to overcome the potential instability of modified electrodes and offers a practical sensing platform for analyzing other heavy-metal anions.

Multi-index assessment of heavy metal contamination in surface sediments of the Pearl River estuary intertidal zone.

Surface sediments from 21 stations within the Pearl River estuary (PRE) intertidal zone were sampled for heavy metal contamination analysis. Average heavy metal concentrations (mg/kg) in the PRE intertidal zone were 118.5 (Cr), 860.4 (Mn), 19.5 (Co), 72.5 (Ni), 128.1 (Cu), 198.5 (Zn), and 73.0 (Pb), with the concentrations of Mn, Co, Ni, Cu, and Zn being significantly higher than their corresponding background values. The enrichment factor (EF) and geo-accumulation index (Igeo) reveal the same contamination status, with Pb, Ni, Co, Mn, and Cu showing slight to moderate contamination. Overall, the combined heavy metal concentration in the PRE intertidal surface sediments had a 24.7 % probability of toxic effects on aquatic biota based on the joint probabilistic risk (JPR) approach. Principal component analysis (PCA) coupled with the correlation analysis (CA) revealed that the heavy metal contamination in the PRE intertidal zone might originate from natural and anthropogenic sources.

Features of gastric cancer by anatomic subsite in northern China: A multi-center Health Science Report database study.

BACKGROUND: The features of gastric cancer based on the anatomic site remain unknown in northern China patients. AIM: To analyze gastric cancer features and associated trends based on the anatomical site in northern China patients. METHODS: This cross-sectional study used incident gastric cancer case data from 10 Peking University-affiliated hospitals (2014 to 2018). The clinical and prevailing local features were analyzed. RESULTS: A total of 10709 patients were enrolled, including antral (42.97%), cardia (34.30%), and stomach body (18.41%) gastric cancer cases. Cancer in the cardia had the highest male:female ratio, proportion of elderly patients, and patients with complications, including hypertension, diabetes, cerebrovascular, and coronary diseases (P < 0.001). gastric cancer involving the antrum showed the lowest proportion of patients from rural areas and accounted for the highest hospitalization rate and cost (each P < 0.001). The proportion of patients with cancer involving the cardia increased with an increase in the number of gastroesophageal reflux disease cases during the same period (P < 0.001). Multivariate analysis revealed that tumor location in the cardia increased the risk of in-hospital mortality (P = 0.046). Anatomical subsite was not linked to postoperative complications. CONCLUSION: The features of gastric cancer based on the anatomical site differ between northern China and other regions, both globally and within the country. Social factors may account for these differences and should affect policy-making and clinical practice.

MicroRNA-582-5p targeting Creb1 modulates apoptosis in cardiomyocytes hypoxia/reperfusion-induced injury.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) caused by the reperfusion therapy of myocardial ischemic diseases is a kind of major disease that threatens human health and lives severely. There are lacking of effective therapeutic measures for MIRI. MicroRNAs (miRNAs) are abundant in mammalian species and play a critical role in the initiation, promotion, and progression of MIRI. However, the biological role and molecular mechanism of miRNAs in MIRI are not entirely clear. METHODS: We used bioinformatics analysis to uncover the significantly different miRNA by analyzing transcriptome sequencing data from myocardial tissue in the mouse MIRI model. Multiple miRNA-related databases, including miRdb, PicTar, and TargetScan were used to forecast the downstream target genes of the differentially expressed miRNA. Then, the experimental models, including male C57BL/6J mice and HL-1 cell line, were used for subsequent experiments including quantitative real-time polymerase chain reaction analysis, western blot analysis, hematoxylin and eosin staining, flow cytometry, luciferase assay, gene interference, and overexpression. RESULTS: MiR-582-5p was found to be differentially upregulated from the transcriptome sequencing data. The elevated levels of miR-582-5p were verified in MIRI mice and hypoxia/reperfusion (H/R)-induced HL-1 cells. Functional experiments revealed that miR-582-5p promoted apoptosis of H/R-induced HL-1 cells via downregulating cAMP-response element-binding protein 1 (Creb1). The inhibiting action of miR-582-5p inhibitor on H/R-induced apoptosis was partially reversed after Creb1 interference. CONCLUSIONS: Collectively, the research findings reported that upregulation of miR-582-5p promoted H/R-induced cardiomyocyte apoptosis by inhibiting Creb1. The potential diagnostic and therapeutic strategies targeting miR-582-5p and Creb1 could be beneficial for the MIRI treatment.