GL-V9 synergizes with oxaliplatin of colorectal cancer via Wee1 degradation mediated by HSP90 inhibition.

OBJECTIVES: GL-V9 exhibited anti-tumour effects on various types of tumours. This study aimed to verify if GL-V9 synergized with oxaliplatin in suppressing colorectal cancer (CRC) and to explore the synergistic mechanism. METHODS: The synergy effect was tested by MTT assays and the mechanism was examined by comet assay, western blotting and immunohistochemistry (IHC). Xenograft model was constructed to substantiated the synergy effect and its mechanism in vivo. RESULTS: GL-V9 was verified to enhance the DNA damage effect of oxaliplatin, so as to synergistically suppress colon cancer cells in vitro and in vivo. In HCT-116 cells, GL-V9 accelerated the degradation of Wee1 and induced the abrogation of cell cycle arrest and mis-entry into mitosis, bypassing the DNA damage response caused by oxaliplatin. Our findings suggested that GL-V9 binding to HSP90 was responsible for the degradation of Wee1 and the vulnerability of colon cancer cells to oxaliplatin. Functionally, overexpression of either HSP90 or WEE1 annulled the synergistic effect of GL-V9 and oxaliplatin. CONCLUSIONS: Collectively, our findings revealed that GL-V9 synergized with oxaliplatin to suppress CRC and displayed a promising strategy to improve the efficacy of oxaliplatin.

Revealing the interaction forms between Hg(II) and group types (-Cl, -CN, -NH2, -OH, -COOH) in functionalized Poly(pyrrole methane)s for efficient mercury removal.

To explore the impact of different functional groups on Hg(II) adsorption, a range of poly(pyrrole methane)s functionalized by -Cl, -CN, -NH2, -OH and -COOH were synthesized and applied to reveal the interaction between different functional groups and mercury ions in water, and the adsorption mechanism was revealed through combined FT-IR, XPS, and DFT calculations. The adsorption performance can be improved to varying degrees by the incorporation of functional groups. Among them, the oxygen-containing functional groups (-OH and -COOH) exhibit stronger affinity for Hg(II) and can increase the adsorption capacity from 180 mg g-1 to more than 1400 mg g-1 at 318 K, with distribution coefficient (Kd) exceeding 105 mL g-1. The variations in the capture and immobilization capabilities of functionalized poly(pyrrole methane)s predominantly stem from the unique interactions between their functional groups and mercury ions. In particular, oxygen-containing -OH and -COOH effectively capture Hg(OH)2 through hydrogen bonding, and further deprotonate to form the -O-Hg-OH and -COO-Hg-OH complexes which are more stable than those obtained from other functionalized groups. Finally, the ecological safety has been fully demonstrated through bactericidal and bacteriostatic experiments to prove the functionalized poly(pyrrole methane)s can be as an environmentally friendly adsorbent for purifying contaminated water.

Decreasing denitrification rates poses a challenge to further decline of nitrogen concentration in Lake Taihu, China.

Nitrogen (N) concentrations in many lakes have decreased substantially in recent years due to external load reduction to mitigate harmful algal blooms. However, little attention has been paid to the linkage between the lakes' nitrogen removal efficiency and improved water quality in lakes, especially the variation of denitrification rate (DNR) under decreasing N concentrations. To understand the efficiency of N removal under improving water quality and its influence on the N control targets in Lake Taihu, a denitrification model based on in situ experimental results was developed and long-term (from 2007 to 2022) water quality and meteorological observations were used to estimate DNR and relate it to the amount of N removal (ANR) from the lake. The concentration of total nitrogen (TN) in Lake Taihu decreased from 3.28 mg L-1 to 1.41 mg L-1 from 2007 to 2022 but the reduction showed spatial heterogeneity. The annual mean DNR decreased from 45.6 µmol m-2 h-1 to 4.2 µmol m-2 h-1, and ANR decreased from 11.85×103 t yr-1 to 1.17×103 t yr-1 during the study years. N budget analysis suggested that the amount of N removed by denitrification accounted for 23.3 % of the external load in 2007, but decreased to only 4.0 % in 2022. Thus, the contribution of N removal by internal N cycling decreased significantly as water quality improved. Notably, the proportion of ANR in winter to total ANR increased from 14 % in 2007 to 23 % in 2022 due to warming. This could potentially lead to N deficiencies in spring and summer, thus limiting the availability of N to phytoplankton. A TN concentration of less than 1.0 mg L-1 in the lake and 1.5 mg L-1 in the inflowing lake zones in spring contribute to local N-limitation in Lake Taihu for cyanobacteria control. Our study revealed a general pattern that N removal efficiency decreases with improved water quality, which is instructive for eutrophic lakes in nitrogen management.

An optical mechanism-based deep learning approach for deriving water trophic state of China's lakes from Landsat images.

Widespread eutrophication has been considered as the most serious environment problems in the world. Given the critical roles of lakes in human society and serious negative effects of water eutrophication on lake ecosystems, it is thus fundamentally important to monitor and assess water trophic status of lakes. However, a reliable model for accurately estimating the trophic state index (TSI) of lakes across a large-scale region is still lacking due to their high complexity. Here, we proposed an optical mechanism-based deep learning approach to remotely estimate TSI of lakes based on Landsat images. The approach consists of two steps: (1) determining the optical indicators of TSI and modeling the relationship between them, and (2) developing an approach for remotely deriving the determined optical indicator from Landsat images. With a large number of in situ datasets measured from lakes (2804 samples from 88 lakes) across China with various optical properties, we trained and validated three machine learning methods including deep neural network (DNN), k-nearest neighbors (KNN) and random forest (RF) to model TSI with the optical indicators and TSI and derive the determined optical indicator from Landsat images. The results showed that (1) the total absorption coefficients of optically active constituents at 440 nm (at-w(440)) performs best in characterizing TSI, and (2) DNN outperforms other models in the inversion of both TSI and at-w(440). Overall, our proposed optical mechanism-based deep learning approach demonstrated a robust and satisfactory performance in assessing TSI using Landsat images (root mean squared error (RMSE) = 5.95, mean absolute error (MAE) = 4.81). This highlights its merit as a nationally-adopted method in lake water TSI estimation, enabling the convenience of the acquisition of water eutrophic information in large scale, thereby assisting us in managing lake ecology. Therefore, we assessed water TSI of 961 lakes (>10 km2) across China using the proposed approach. The resulting at-w(440) and TSI ranged from 0.01 m-1 to 31.42 m-1 and from 6 to 96, respectively. Of all these studied lakes, 96 lakes (11.40 %) were oligotrophic, 338 lakes were mesotrophic (40.14 %), 360 lakes were eutrophic (42.76 %), and 48 were hypertrophic (5.70 %) in 2020.

Paclitaxel combined with Compound K inducing pyroptosis of non-small cell lung cancer cells by regulating Treg/Th17 balance.

BACKGROUND: Immune checkpoint inhibitors, which have attracted much attention in recent years, have achieved good efficacy, but their use is limited by the high incidence of acquired drug resistance. Therefore, there is an urgent need to develop new immunotherapy drugs. Compound taxus chinensis capsule (CTC) is an oral paclitaxel compound drug, clinical results showed it can change the number of regulatory T cells and T helper cell 17 in peripheral blood. Regulating the balance between regulatory T cells and T helper cell 17 is considered to be an effective anticancer strategy. Paclitaxel and ginsenoside metabolite compound K are the main immunomodulatory components, it is not clear that paclitaxel combined with compound K can inhibit tumor development by regulating the balance between regulatory T cell and T helper cell 17. METHODS: MTT, EdU proliferation and plate colony formation assay were used to determine the concentration of paclitaxel and compound K. AnnexinV-FITC/PI staining, ELISA, Western Blot assay, Flow Cytometry and Immunofluorescence were used to investigate the effect of paclitaxel combined with compound K on Lewis cell cultured alone or co-cultured with splenic lymphocyte. Finally, transplanted tumor C57BL/6 mice model was constructed to investigate the anti-cancer effect in vivo. RESULTS: According to the results of MTT, EdU proliferation and plate colony formation assay, paclitaxel (10 nM) and compound K (60 µM) was used to explore the mechanism. The results of Flow Cytometry demonstrated that paclitaxel combined with compound K increased the number of T helper cell 17 and decreased the number of regulatory T cells, which induced pyroptosis of cancer cells. The balance was mediated by the JAK-STAT pathway according to the results of Western Blot and Immunofluorescence. Finally, the in vivo results showed that paclitaxel combined with compound K significantly inhibit the progression of lung cancer. CONCLUSIONS: In this study, we found that paclitaxel combined with compound K can activate CD8+ T cells and induce pyroptosis of tumor cells by regulating the balance between regulatory T cells and T helper cell 17. These results demonstrated that this is a feasible treatment strategy for lung cancer.

miR615-3p inhibited FBLN1 and osteogenic differentiation of umbilical cord mesenchymal stem cells by associated with YTHDF2 in a m6 A-miRNA interaction manner.

To investigate the role and mechanism of FBLN1 in the osteogenic differentiation and bone regeneration by using umbilical cord mesenchymal stem cells (WJCMSCs). We found that FBLN1 promoted osteogenic differentiation of WJCMSCs and WJCMSC-mediated bone regeneration. It was showed that there was an m6 A methylation site in 3'UTR of FBLN1 mRNA, and the mutation of the m6 A site enhanced the stability of FBLN1 mRNA, subsequently fostering the FBLN1 enhanced osteogenic differentiation of WJCMSCs. YTHDF2 was identified as capable of recognizing and binding to the m6 A site, consequently inducing FBLN1 instability and repressed the osteogenic differentiation of WJCMSCs. Meanwhile, miR-615-3p negatively regulated FBLN1 by binding FBLN1 3'UTR and inhibited the osteogenic differentiation of WJCMSCs and WJCMSC-mediated bone regeneration. Then, we discovered miR-615-3p was found to regulate the functions of FBLN1 facilitated by YTHDF2 through an m6 A-miRNA regulation mechanism. We demonstrated that FBLN1 is critical for regulating the osteogenic differentiation potentials of WJCMSCs and have identified that miR615-3p mediated the decay of FBLN1 mRNA which facilitated by m6 A reading protein YTHDF2. This provided a novel m6 A-miRNA epigenetic regulatory pattern for MSC regulation and bone regeneration.

[Factors Influencing the Variation in Phytoplankton Functional Groups in Fuchunjiang Reservoir].

To explore the distribution characteristics, blooming risk mechanism and driving factors of phytoplankton community structure in Fuchunjiang Reservoir. The variation characteristics of phytoplankton, zooplankton and physicochemical indicators in Fuchunjiang Reservoir and its upper and lower reaches were investigated in 2020 and 2021. Based on the phytoplankton functional groups, non-metric multidimensional scale analysis, redundancy analysis and other statistical methods, the seasonal succession characteristics and driving factors of phytoplankton functional groups were analyzed. A total of 18 phytoplankton functional groups were identified, in of which 10 were predominant. The composition of phytoplankton functional groups in the Fuchunjiang Reservoir was significant different. Spatially, the upstream were dominated by group C and P while the represent species were Cyclotella and Aulacoseira,reflecting the mixed meso-eutrophic environments. However, group P was the main group in Fuchunjiang reservoir, and the dominance decreased gradually along the stream direction. Meanwhile, in the downstream, MP has an absolute advantage at Qiantang River estuary. It reflected the environmental characteristics of frequent disturbance and high turbidity of tide-sensing rivers. In addition, the predominant functional groups demonstrated strong seasonal variations. The dominant functional groups were diverse in summer and consisted of P+L0+J+M+S1+H1+MP. In addition to group P (Aulacoseira), which was dominant throughout the year, it also included several groups represented by cyanobacteria and chlorophyta, reflecting the environmental characteristics of changeable habitats and vigorous productivity. In autumn, the succession was dominated by H1 group represented by Dolichospermum and the representative function groups were P and H1, reflecting the hydrological background of reduced flow and static flow. In winter, the increase of Cyclotella led to the predominance of group C, which was dominated by P+C, reflecting the changing conditions of weakened water exchange and intensified eutrophication problems. In spring, the dominant functional groups were gradually enriched and were composed of C, D, P, and MP, which also reflected the changing environmental habitat characteristics which caused by increasing rainfall and air temperature. According to the results of the C-R-S growth strategy, the Fuchunjiang Reservoir has been in the R strategy for a long time, which was consistent with the habitat characteristics of Fuchunjiang Reservoir and its upper and lower reaches with high disturbance and low stress. In addition, C strategy and S strategy appeared in some reaches, reflecting the variability of water quality and hydrology. RDA analysis showed that water temperature, discharge, zooplankton biomass, permanganate index, total nitrogen and total phosphorus were significantly correlated with the seasonal succession of phytoplankton functional groups (P < 0.05), and temperature and flow pattern were probably the most critical factors for the succession. Studies have shown that the impact of hydrometeorological processes on phytoplankton in the Fuchunjiang Reservoir is crucial:high temperature and changing discharge during the summer may lead to cyanobacterial blooms in the Fuchunjiang reservoir; To reduce the risk of algal blooms, it is still necessary to increase the control of nitrogen and phosphorus load in rivers, and fully consider the coordination of water conservancy dispatch methods.

Pulmonary delivery of nano-particles for lung cancer diagnosis and therapy: Recent advances and future prospects.

Although our understanding of lung cancer has significantly improved in the past decade, it is still a disease with a high incidence and mortality rate. The key reason is that the efficacy of the therapeutic drugs is limited, mainly due to insufficient doses of drugs delivered to the lungs. To achieve precise lung cancer diagnosis and treatment, nano-particles (NPs) pulmonary delivery techniques have attracted much attention and facilitate the exploration of the potential of those in inhalable NPs targeting tumor lesions. Since the therapeutic research focusing on pulmonary delivery NPs has rapidly developed and evolved substantially, this review will mainly discuss the current developments of pulmonary delivery NPs for precision lung cancer diagnosis and therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

LW-213 induces immunogenic tumor cell death via ER stress mediated by lysosomal TRPML1.

Dying tumor cells release biological signals that exhibit antigenicity, activate cytotoxic T lymphocytes, and induce immunogenic cell death (ICD), playing a key role in immune surveillance. We demonstrate that the flavonoid LW-213 activates endoplasmic reticulum stress (ERS) in different tumor cells and that the lysosomal calcium channel TRPML1 mediates the ERS process in human cellular lymphoma Hut-102 cells. Apoptotic tumor cells induced by ERS often possess immunogenicity. Tumor cells treated with LW-213 exhibit damage-associated molecular patterns (DAMPs), including calreticulin translocation to the plasma membrane and extracellular release of ATP and HMGB1. When co-cultured with antigen-presenting cells (APCs), LW-213-treated tumor cells activated APCs. Two groups of C57BL/6J mice were inoculated with Lewis cells: a "vaccine group", which demonstrated that LW-213-treated tumor cells promote the maturation of dendritic cells and increase CD8+ T cells infiltration in the tumor microenvironment and a "pharmacodynamic group", treated with a combination of LW-213 and PD1/PD-L1 inhibitor (BMS-1), which reduced tumor growth and significantly prolonged the survival time of mice in the "pharmacodynamic group". Therefore, LW-213 can be developed as a novel ICD inducer, providing a new concept for antitumor immunotherapy.

Distribution, sources, and risk analysis of heavy metals in sediments of Xiaoqing River basin, Shandong province, China.

The accumulation of heavy metals in river sediment poses a major threat to ecological safety. The Xiaoqing River originates in western Jinan, with higher population density and per capita gross domestic product (GDP) in its basin compared to the Shandong province average. This study analyzed the spatial characteristics, ecological risk, human health risk, and contamination sources of heavy metals by collecting sediment samples from Xiaoqing River. We use the methods such as geo-accumulation index (Igeo), ecological risk assessment based on the interval number sorting method, and health risk assessment to evaluate the risk of heavy metals in sediments. The research finding suggests heavy metals including Pb, As, Ni, and Cr are low ecological risks, while Hg and Cd have reached high and extreme ecological risks. Correlation analysis and principal component analysis were used to analyze the correlation and sources of different heavy metals. The six heavy metals were categorized into three groups. Factor 1, comprising Hg, Cr, and Pb, was identified as a mixed source with a contribution rate of 37.76%. Factor 2 is an agricultural source and comprises Ni, Cd, and As with a contribution rate of 27.05%. Factor 3 includes Pb and Ni contributing to 15.30% as a natural source. This study offers valuable insights for the prevention of heavy metal pollution, as well as promoting sustainable urban development.

A critical review on quantitative evaluation of aqueous toxicity in water quality assessment.

Conventional chemical techniques have inherent limitations in detecting unknown chemical substances in water. As a result, effect-based methods have emerged as a viable alternative to overcome these limitations. These methods provide more accurate and intuitive evaluations of the toxic effects of water. While numerous studies have been conducted, only a few have been applied to national water quality monitoring. Therefore, it is crucial to develop toxicity evaluation methods and establish thresholds based on quantifying toxicity. This article provides an overview of the development and application of bioanalytical tools, including in vitro and in vivo bioassays. The available methods for quantifying toxicity are then summarized. These methods include aquatic life criteria for assessing the toxicity of a single compound, comprehensive wastewater toxicity testing for all contaminants in a water sample (toxicity units, whole effluent toxicity, the potential ecotoxic effects probe, the potential toxicology method, and the lowest ineffective dilution), methods based on mechanisms and relative toxicity ratios for substances with the same mode of action (the toxicity equivalency factors, toxic equivalents, bioanalytical equivalents), and effect-based trigger values for micropollutants. The article also highlights the advantages and disadvantages of each method. Finally, it proposes potential areas for applying toxicity quantification methods and offers insights into future research directions. This review emphasizes the significance of enhancing the evaluation methods for assessing aqueous toxicity in water quality assessment.

[Influence of Denitrification on Cyanobacterial Blooms Trends in Lake Taihu, China].

Denitrification is a major process in aquatic ecosystems, and it competes with cyanobacterial growth for nitrogen. However, the effect of denitrification on cyanobacterial blooms under the background of climate change remains unclear. This study explored the interaction between lake denitrification and formation of cyanobacterial blooms, using the historical water quality monitoring data of North Lake Taihu over five years from 2017 to 2021 and via incubation experiments of cyanobacteria and sediment denitrification. The monitoring data showed that algal biomass (Chla as a proxy) primarily peaked during summer and autumn. The seasonal variations in total N concentration showed a completely opposite trend than that of algal biomass, which peaked in winter and spring. Nitrate was the major component of dissolved inorganic nitrogen, and the nitrate concentration was approximately zero in summer and autumn. The total phosphorus concentration varied in the same way as the Chla concentration. The experimental results showed that Cyanobacteria did not grow when the temperature was below 20℃. In comparison, denitrification showed a significant linear relationship with temperatures between 10-25℃ (R2=0.99) and reached the maximum value of (62.98±21.36) µmol·(kg·h)-1 in Lake Taihu at 25℃. Additionally, the nitrate concentration threshold at the maximum denitrification rate was 4 mg·L-1. Cyanobacteria assimilate nitrate for growth, thereby reducing the concentration of nitrate required for denitrification. This study indicated that the advance in lake temperature warming due to climate change may result in earlier growth of cyanobacteria, thereby leading to large amounts of N being assimilated by algae before denitrification, further affecting the dynamics of cyanobacterial blooms. The present results are scientifically important for explaining the mechanism of cyanobacterial bloom rebound in Lake Taihu under the background of recent climate changes.

RING box protein-1(RBX1), a key component of SCF E3 ligase, induced multiple myeloma cell drug-resistance though suppressing p27.

Multiple myeloma (MM) is a clonal disease of plasma cells that remains, for the most part, incurable despite the advent of several novel therapeutics. The elevated expression of p27 and its association with cell-cycle arrest is speculated to be one of the major mechanisms by which MM cells escape the cytotoxic effects of therapeutic agents. In this study, we demonstrated that RBX1 silencing could inhibit MM cell growth and promote cell drug resistance. RBX1 directly interacted with and triggered the ubiquitination and degradation of p27, ultimately causing p27 reduction. Additionally, cell growth and apoptosis analysis indicated that the role of RBX1 in regulating myeloma cell proliferation and drug resistance resulted from p27 accumulation, which occurred in a Thr187 phosphorylation-dependent manner. Furthermore, the cell-cycle analysis demonstrated that RBX1 overexpression induced cells to enter the cell cycle (S-phase) and partially inhibited chemotherapeutic drugs-mediated cell cycle arrest. Notably, the forced expression of RBX1 also inhibited the cell adhesion-mediated elevation of p27 and induced the accumulation of adherent cells in apoptosis, especially the proteolytic cleavage of caspase-3. Additionally, RBX1 knockdown significantly inhibited myeloma development in SCID-Hu mice and in a human MM xenotransplant model. Overall, these in vitro and in vivo experiments indicated that the RBX1-p27 axis could be a central molecular mechanism by which RBX1 functions as a tumor promoter and stimulates cell growth in chemotherapeutic drugs treated MM cells.

Extracellular vesicles derived from human dental mesenchymal stem cells stimulated with low-intensity pulsed ultrasound alleviate inflammation-induced bone loss in a mouse model of periodontitis.

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have emerged as a new mode of intercellular crosstalk and are responsible for many of the therapeutic effects of MSCs. To promote the application of MSC-EVs, recent studies have focused on the manipulation of MSCs to improve the production of EVs and EV-mediated activities. The current paper details an optimization method using non-invasive low-intensity pulsed ultrasound (LIPUS) as the stimulation for improving oral MSC-EV production and effectiveness. Stem cells from apical papilla (SCAP), a type of oral mesenchymal stem cell, displayed intensity-dependent pro-osteogenic and anti-inflammatory responses to LIPUS without significant cytotoxicity or apoptosis. The stimuli increased the secretion of EVs by promoting the expression of neutral sphingomyelinases in SCAP. In addition, EVs from LIPUS-induced SCAP exhibited stronger efficacy in promoting the osteogenic differentiation and anti-inflammation of periodontal ligament cells in vitro and alleviating oral inflammatory bone loss in vivo. In addition, LIPUS stimulation affected the physical characteristics and miRNA cargo of SCAP-EVs. Further investigations indicated that miR-935 is an important mediator of the pro-osteogenic and anti-inflammatory capabilities of LIPUS-induced SCAP-EVs. Taken together, these findings demonstrate that LIPUS is a simple and effective physical method to optimize SCAP-EV production and efficacy.

Responses of soil microbes and enzymes to long-term warming incubation in different depths of permafrost peatland soil.

Soil microbes and enzymes mediate soil carbon-climate feedback, and their responses to increasing temperature partly affect soil carbon stability subjected to the effects of climate change. We performed a 50-month incubation experiment to determine the effect of long-term warming on soil microbes and enzymes involved in carbon cycling along permafrost peatland profile (0-150 cm) and investigated their response to water flooding in the active soil layer. Soil bacteria, fungi, and most enzymes were observed to be sensitive to changes in temperature and water in the permafrost peatland. Bacterial and fungal abundance decreased in the active layer soil but increased in the deepest permafrost layer under warming. The highest decrease in the ratio of soil bacteria to fungi was observed in the deepest permafrost layer under warming. These results indicated that long-term warming promotes recalcitrant carbon loss in permafrost because fungi are more efficient in decomposing high-molecular-weight compounds. Soil microbial catabolic activity measured using Biolog Ecoplates indicated a greater degree of average well color development at 15 °C than at 5 °C. The highest levels of microbial catabolic activity, functional diversity, and carbon substrate utilization were found in the permafrost boundary layer (60-80 cm). Soil polyphenol oxidase that degrades recalcitrant carbon was more sensitive to increases in temperature than ß-glucosidase, N-acetyl-ß-glucosaminidase, and acid phosphatase, which degrade labile carbon. Increasing temperature and water flooding exerted a synergistic effect on the bacterial and fungal abundance and ß-glucosidase, acid phosphatase, and RubisCO activity in the topsoil. Structural equation modeling analysis indicated that soil enzyme activity significantly correlated with ratio of soil bacteria to fungi and microbial catabolic activity. Our results provide valuable insights into the linkage response of soil microorganisms, enzymes to climate change and their feedback to permafrost carbon loss.

Correlation between childhood trauma experience and depressive symptoms among young adults: The potential mediating role of loneliness.

BACKGROUND: It is widely recognized that childhood trauma poses a significant risk of developing depressive symptoms. However, the underlying mediation mechanism between childhood trauma and depressive symptoms requires further exploration. OBJECTIVE: This study focuses on exploring whether loneliness may act as a potential mediator between childhood trauma and depressive symptoms. PARTICIPANTS AND SETTING: We analyzed a large sample of college students (N = 7293). Participants completed online questionnaires in the WeChat group. METHODS: Childhood trauma, depressive symptoms, and loneliness were evaluated using the Childhood Trauma Questionnaire-Short Form (CTQ-SF), the Patient Health Questionnaire-9 (PHQ-9), and the University of California Los Angeles Loneliness Scale (UCLA-LS) respectively. The linear regression method was applied to explore the mediating role. RESULTS: Gender, relationship with family, and left-behind experience are all substantial depressive symptoms risk factors. Childhood trauma was shown to be highly related to depressive symptoms, and this relationship was potentially mediated by loneliness. CONCLUSIONS: Our research indicates that treating loneliness in those who have undergone childhood trauma may help prevent or treat depressive symptoms. Therefore, loneliness should be taken into consideration while treating and preventing depressive symptoms.

Bloom-induced internal release controlling phosphorus dynamics in large shallow eutrophic Lake Taihu, China.

High phosphorus (P) concentrations are commonly observed in lakes during algal blooms despite massive efforts on external nutrient reduction. However, the knowledge about the relative contribution of internal P loading linked with algal blooms on lake phosphorus (P) dynamics remains limited. To quantify the effect of internal loading on P dynamics, we conducted extensive spatial and multi-frequency nutrient monitoring from 2016 to 2021 in Lake Taihu, a large shallow eutrophic lake in China, and its tributaries (2017-2021). The in-lake P stores (ILSP) and external loading were estimated and then internal P loading was quantified from the mass balance equation. The results showed that the in-lake total P stores (ILSTP) ranged from 398.5 to 1530.2 tons (t), and exhibited a dramatic intra- and inter-annual variability. The annual internal TP loading released from sediment ranged from 1054.3 to 1508.4 t, which was equivalent to 115.6% (TP loading) of the external inputs on average, and responsible for the fluctuations of ILSTP on a weekly scale. High-frequency observations exemplified that ILSTP increased by 136.4% during algal blooms in 2017, while by only 47.2% as a result of external loading after heavy precipitation in 2020. Our study demonstrated that both bloom-induced internal loading and storm-induced external loading are likely to run counter significantly to watershed nutrient reduction efforts in large shallow lakes. More importantly, bloom-induced internal loading is higher than storm-induced external loading over the short term. Given the positive feedback loop between internal P loadings and algal bloom in eutrophic lakes, which explains the significant fluctuation of P concentration while nitrogen concentration decreased. It is emphasized that internal loading and ecosystem restoration are unignorable in shallow lakes, particularly in the algal-dominated region.

External Fields Assisted Highly Efficient Oxygen Evolution Reaction of Confined 1T-VSe2 Ferromagnetic Nanoparticles.

As a clean and effective approach, the introduction of external magnetic fields to improve the performance of catalysts has attracted extensive attention. Owing to its room-temperature ferromagnetism, chemical stability, and earth abundance, VSe2 is expected to be a promising and cost-effective ferromagnetic electrocatalyst for the accomplishment of high-efficient spin-related OER kinetics. In this work, a facile pulsed laser deposition (PLD) method combined with rapid thermal annealing (RTA) treatment is used to successfully confine monodispersed 1T-VSe2 nanoparticles in amorphous carbon matrix. As expected, with external magnetic fields of 800 mT stimulation, the confined 1T-VSe2 nanoparticles exhibit highly efficient oxygen evolution reaction (OER) catalytic activity with an overpotential of 228 mV for 10 mA cm-2 and remarkable durability without deactivation after >100 h OER operation. The experimental results together with theoretical calculations illustrate that magnetic fields can facilitate the surface charge transfer dynamics of 1T-VSe2 , and modify the adsorption-free energy of *OOH, thus finally improving the intrinsic activity of the catalysts. This work realizes the application of ferromagnetic VSe2 electrocatalyst in highly efficient spin-dependent OER kinetics, which is expected to promote the application of transition metal chalcogenides (TMCs) in external magnetic field-assisted electrocatalysis.

Targeting lysosomal HSP70 induces acid sphingomyelinase-mediated disturbance of lipid metabolism and leads to cell death in T cell malignancies.

BACKGROUND: T cell malignancies proliferate vigorously, are highly dependent on lysosomal function, with limited therapeutic options. Deregulation of lysosomal structure and function has been confirmed to be a key role in the treatment of hematologic malignant disease. METHODS: Cell counting kit 8 and Annexin V/PI staining were used to assess the cell viability and apoptosis rate. Flow cytometry, liquid chromatography mass spectrometry, immunofluorescence and western blot were performed to detect the effect on lysosomes. Drug affinity responsive target stability, molecular docking and cellular thermal shift assay were employed to confirm the target protein of V8 on lysosomes. A xenograft model was constructed in NOD/SCID mice to assess the effect and mechanism. RESULTS: V8, a new lysosomotropic compound, could be rapidly trapped by lysosomes and accumulation in lysosomes, contributing to lysosomal-dependent cell death by evoking lysosomal membrane permeabilization (LMP), accompanied with disrupted lysosome and autophagic flux. Mechanistically, heat shock protein 70 (HSP70) was identified as the binding target of V8 in lysosome. As a downstream effect of targeting HSP70, enzymatic activity of acid sphingomyelinase (ASM) was inhibited, which induced disturbance of lipid metabolism, instability of lysosomal membrane, and leakage of cathepsin B and D, leading to LMP-mediated cell death. In vivo study showed V8 well controlled the growth of the tumour and confirmed lysosomal cell death induced by V8. CONCLUSIONS: Collectively, this study suggests targeting lysosomal HSP70-ASM axis by V8 illustrates the great value of drug therapy for T cell malignancies and the unlimited potential of lysosomal targeting for cancer therapy.

Perfluorobutanesulfonate exposure induces metabolic disturbances in different regions of mouse gut.

Perfluorobutanesulfonate (PFBS), an alternative to perfluorooctanesulfonate (PFOS), has raised many health concerns. However, PFBS toxicity in the mammalian gut remains unclear. C57BL/6 mice were exposed to 10 µg/L and 500 µg/L PFBS or 500 µg/L PFOS in their water supply for 28 days. PFBS toxicity in the ileum and colon was explored and compared to that of PFOS. Biochemical analysis showed that tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels increased in the ileum exposed to 10 µg/L PFBS, whereas no significant changes were observed in those levels in the colon. Catalase (CAT) activity, malondialdehyde (MDA), TNF-α, and IL-1ß levels increased and glutathione (GSH) levels decreased in the ileum of the 500 µg/L-PFBS group, whereas only MDA levels increased in the colon of the 500 µg/L-PFBS group. The results showed that more severe damage occurred in the ileum than in the colon after PFBS exposure, and these align with the 500 µg/L-PFOS group exposure as well. Furthermore, metabolomic analysis revealed glutathione metabolism as a vital factor in inducing PFBS and PFOS toxicities in the ileum. Steroid hormone and amino acid metabolisms were other important factors involved in PFBS and PFOS toxicities, respectively. In the colon, GSH, pyrimidine, and glucose (especially galactose) metabolism was the main contributor to PFBS toxicity, and sulfur amino acid metabolism was the main pathway for PFOS toxicity. This study provides more evidence of the health hazards due to low-dose PFBS exposure in the mammalian gut.