Trajectory of Caregiver Burden and Associated Factors in Family Caregivers of Individuals with Colorectal Cancer: A Longitudinal, Observational Multicenter Study.

Purpose: To (1) investigate the changes in 5 domains (lack of family support, impact on finance, impact on daily schedule, impact on health, and self-esteem) of family caregiver (FC) burden and overall burden for first diagnosed colorectal cancer; (2) exploring changes in FC burden for colorectal cancer patients over time and analyze the trajectory and sub-trajectories of FC burden; and (3) identify the FC-related and patient-related factors most associated with the overall FC burden and each of its sub-trajectories. Patients and methods: This study is a descriptive longitudinal study. A convenience sampling method was used to recruit patients with colorectal cancer and their primary FCs from seven hospitals. Results: A total of 185 pairs of first diagnosed colorectal cancer patient and their FC were investigated for 4 times. The results reveal the overall burden and 5 domains of burden showed a trend of increasing first and then decreasing, and the burden was the heaviest at the time in the middle of chemotherapy. In the course of time, the aspect that caused the greatest amount of burden on average transitioned from the "effect on daily schedule" (range= 3.3 and 3.9) to the "effect on finances" (range= 3.1 to 3.4). Conclusion: Almost 88% of FCs have a either a moderate or a high level of burden. The quality of life of patients and the self-efficacy, social support and care ability of FCs have a great impact on the overall FC burden and each sub-trajectory.

Efficacy and Safety of Epidural Chloroprocaine for Breakthrough Pain During Labor Analgesia: A Prospective, Double-Blind, Randomized Trial.

INTRODUCTION: A significant number of women who undergo neuraxial labor analgesia experience breakthrough pain. Prompt mitigation of breakthrough pain is essential to improve maternal and fetal outcomes. We evaluated epidural chloroprocaine compared with ropivacaine in alleviating labor breakthrough pain. METHODS: We performed a double-blind randomized controlled clinical trial between May and July 2023. Eligible parturients received epidural analgesia with ropivacaine and sufentanil. Those with breakthrough pain were randomized to receive either 0.125% epidural ropivacaine (group R) or chloroprocaine at concentrations of 0.5% (group C1), 1.0% (group C2), or 1.5% (group C3), all in a volume of 6 mL. The primary outcome was the treatment success rate, indicated by a decrease of at least 4 points on the numerical rating scale pain score 9 min after analgesic injection. Secondary outcomes and adverse effects were also recorded. RESULTS: Out of 323 patients receiving epidural analgesia, 192 experienced breakthrough pain. After exclusion of three patients because of protocol deviation, there were 47, 48, 47, and 47 patients in group R, C1, C2, and C3, respectively. Group C3 demonstrated a higher treatment success rate (39/47, 83.0%) in managing breakthrough pain than group R (26/47, 55.3%), group C1 (12/48, 25.0%), and group C2 (30/47, 63.8%) (p < 0.001). Group C3 had lower numerical rating scale scores at 6 and 9 min after injection and required fewer patient-controlled epidural boluses than other groups. In addition, group C3 reported greater satisfaction than the other groups (p < 0.001). No significant differences were observed in obstetric or neonatal outcomes across these groups. CONCLUSION: Parturients experiencing breakthrough pain could receive 1.5% epidural chloroprocaine, rather than lower chloroprocaine concentrations and ropivacaine, to achieve more rapid and better pain relief with higher patient satisfaction. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2300071069, http://www.chictr.org.cn/index.aspx .

Elevation of H3K27me3 level contributes to the radioresistance of nasopharyngeal carcinoma by inhibiting OAS1 expression.

Radiotherapy has long been a main treatment option for nasopharyngeal carcinoma (NPC). However, during clinical treatment, NPC is prone to developing radioresistance, resulting in treatment failure. This study aims to examine the role of histone methylation in the induction of radioresistance. It was found that the radioresistance of NPC cells was related to the increase of the level of histone H3 lysine 27 trimethylation (H3K27me3). Treatment of cells with histone methyltransferase inhibitor GSK126 increased the radiosensitivity of NPC cells by triggering Bcl2 apoptosis regulator/BCL2-associated X, apoptosis regulator (Bcl2/BAX) signaling pathway. Bioinformatics analysis indicated that the expression of 2'-5'-oligoadenylate synthetase 1 (OAS1) was reduced in the radioresistant cells but increased in the GSK126-treated cells. Chromatin immunoprecipitation assay confirmed that the decrease of OAS1 expression in radioresistant cells was mainly due to the enrichment of H3K27me3 in its promoter region. Furthermore, downregulation of OAS1 reduced apoptosis due to the inhibition of Bcl2/BAX pathway after irradiation, while OAS1 overexpression increased radiosensitivity. Our findings revealed for the first time that the increase of H3K27me3 level was associated with the decrease of OAS1 expression, leading to the inhibition of apoptosis and ultimately contributing to the radioresistance of NPC cells. Moreover, the histone methyltransferase inhibitor GSK126 could overcome the radioresistance and thus might be a potential therapeutic strategy for NPC.NEW & NOTEWORTHY Our findings revealed for the first time that the increase of H3K27me3 level was associated with the decrease of OAS1 expression, leading to the inhibition of apoptosis and ultimately contributing to the radioresistance of NPC cells. Moreover, we demonstrated that the histone methyltransferase inhibitor GSK126 could be a promising therapeutic strategy for NPC by overcoming radioresistance, providing valuable insights into the clinical treatment of NPC.

Source-based health risk assessment of heavy metal contamination in soil: a case study from a polymetallic mining region in Southeastern Hubei, Central China.

To conduct a precise health risk assessment of heavy metals (HMs) in soil, it is imperative to ascertain the primary sources of potential health risks. In this study, we conducted comprehensive measurements of HMs, specifically focusing on the accumulation of Cu, Cd, Sb, Zn, and Pb in local soil, which may pose threats to environmental quality. To achieve our objective, we employed a method that combines positive matrix factorization with a health risk assessment model to quantify the health risks associated with specific sources. The results obtained from the geo-accumulation index indicate that the majority of HMs found in the local soil are influenced by anthropogenic activities. Among these sources, local industrial-related activities contributed the largest proportion of HMs to the soil at 34.7%, followed by natural sources at 28.7%, mining and metallurgy-related activities at 28.2%, and traffic-related activities at 8.40%. Although the non-carcinogenic and carcinogenic risks associated with individual HMs were found to be below safety thresholds, the cumulative health risks stemming from total HMs exceeded safety limits for children. Moreover, the unacceptable health risks for children originating from industrial-related activities, natural sources, and mining and metallurgy-related activities were primarily concentrated in proximity to mining sites and industrial areas within the local region. This investigation furnishes valuable insights that can aid governmental authorities in formulating precise control policies to mitigate health threats posed by soils in polymetallic mining areas.

Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches.

Non-small cell lung cancer (NSCLC) is often driven by mutations in the epidermal growth factor receptor (EGFR) gene. However, rare mutations such as G719X and S768I lack standard anti-EGFR targeted therapies. Understanding the structural differences between wild-type EGFR and these rare mutants is crucial for developing EGFR-targeted drugs. We performed a systematic analysis using molecular dynamics simulations, essential dynamics (ED), molecular mechanics Poisson-Boltzmann surface area, and free energy calculation methods to compare the kinetic properties, molecular motion, and free energy distribution between wild-type EGFR and the rare mutants' structures G719X-EGFR, S768I-EGFR, and G719X + S768I-EGFR. Our results showed that S768I-EGFR and G719X + S768I-EGFR have higher global and local conformational flexibility and lower thermal and global structural stability than WT-EGFR. ED analysis revealed different molecular motion patterns between S768I-EGFR, G719X + S768I-EGFR, and WT-EGFR. The A-loop and αC-helix, crucial structural elements related to the active state, showed a tendency toward active state development, providing a molecular mechanism explanation for NSCLC caused by EGFR S768I and EGFR G719C + S768I mutations. The present study may be helpful in the development of new EGFR-targeted drugs based on the structure of rare mutations. Our findings may aid in developing new targeted treatments for patients with EGFR S768I and EGFR G719X + S768I mutations.

Endogenous hydrogen sulfide inhibition suppresses tumor growth by promoting apoptosis and pyroptosis in esophageal cancer cells.

BACKGROUND: Hydrogen sulfide (H2S) has been identified as the third gaseous signaling molecule. Endogenous H2S plays a key role in the progression of various types of cancer. However, the effect of endogenous H2S on the growth of esophageal cancer (EC) remains unknown. METHODS: In this study, three kinds of H2S-producing enzymes inhibitors, DL-propargylglycine (PAG, inhibitor of cystathionine-γ-lyase), aminooxyacetic acid (AOAA, inhibitor of cystathionine-ß-synthase), and L-aspartic acid (L-Asp, inhibitor of 3-mercaptopyruvate sulfurtransferase) were used to determine the role of endogenous H2S in the growth of EC9706 and K450 human EC cells. RESULTS: The results indicated that the combination (PAG+AOAA+L-Asp) group showed higher inhibitory effects on the viability, proliferation, migration, and invasion of EC cells than PAG, AOAA, and L-Asp group. Inhibition of endogenous H2S promoted apoptosis via activation of mitogen-activated protein kinase pathway in EC cells. Endogenous H2S suppression triggered pyroptosis of EC cells by activating reactive oxygen species-mediated nuclear factor-κB signaling pathway. In addition, the combine group showed its more powerful growth-inhibitory effect on the growth of human EC xenograft tumors in nude mice without obvious toxicity. CONCLUSION: Our results indicate that inhibition of endogenous H2S production can significantly inhibit human EC cell growth via promotion of apoptosis and pyroptosis. Endogenous H2S may be a promising therapeutic target in EC cells. Novel inhibitors for H2S-producing enzymes can be designed and developed for EC treatment.

Bromine-Enhanced Generation and Epoxidation of Ethylene in Tandem CO2 Electrolysis Towards Ethylene Oxide.

The indirect electro-epoxidation of ethylene (C2 H4 ), produced from CO2 electroreduction (CO2 R), holds immense promise for CO2 upcycling to valuable ethylene oxide (EO). However, this process currently has a mediocre Faradaic efficiency (FE) due to sluggish formation and rapid dissociation of active species, as well as reductive deactivation of Cu-based electrocatalysts during the conversion of C2 H4 to EO and CO2 to C2 H4 , respectively. Herein, we report a bromine-induced dual-enhancement strategy designed to concurrently promote both C2 H4 -to-EO and CO2 -to-C2 H4 conversions, thereby improving EO generation, using single-atom Pt on N-doped CNTs (Pt1 /NCNT) and Br- -bearing porous Cu2 O as anode and cathode electrocatalysts, respectively. Physicochemical characterizations including synchrotron X-ray absorption, operando infrared spectroscopy, and quasi in situ Raman spectroscopy/electron paramagnetic resonance with theoretical calculations reveal that the favorable Br2 /HBrO generation over Pt1 /NCNT with optimal intermediate binding facilitates C2 H4 -to-EO conversion with a high FE of 92.2 %, and concomitantly, the Br- with strong nucleophilicity protects active Cu+ species in Cu2 O effectively for improved CO2 -to-C2 H4 conversion with a FE of 66.9 % at 800 mA cm-2 , superior to those in the traditional chloride-mediated case. Consequently, a single-pass FE as high as 41.1 % for CO2 -to-EO conversion can be achieved in a tandem system.

Comparative efficacy of mind-body exercise for depression in breast cancer survivors: A systematic review and network meta-analysis.

BACKGROUND: As pharmacotherapy often leads to adverse reactions, mind-body exercise (MBE) treatments have become a more popular option for treating depression in people living with breast cancer (BC). However, the most effective type of MBE treatment for this population remains unclear. AIMS: The aim of this systematic review and network meta-analysis (NMA) was to compare the efficacy of the different MBE modes for depression in people with BC. METHODS: A systematic search for randomized controlled trials (RCTs) from inception to March 25, 2023, was conducted in the following database: EMBASE, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine, OpenGrey, and ClinicalTrials.gov. A traditional meta-analysis was conducted using the random-effects model to directly assess the effectiveness of various MBE interventions. Stata 16.0 software was used for performing the NMA. RESULTS: The NMA was performed in 32 eligible RCTs including 2361 participants. The efficacy of MBE treatments on depression was ranked as the following: Liuzijue (surface under the cumulative ranking curve [SUCRA] = 95.4%) > Tai chi (SUCRA = 76.9%) > yoga (SUCRA = 55.0%) > Baduanjin (SUCRA = 53.9%) > Pilates (SUCRA = 38.6%) > dance (SUCRA = 30.2%) > Qigong (SUCRA = 28.1%) > control (SUCRA = 21.9%). LINKING EVIDENCE TO ACTION: Our research showed that Liuzijue and Tai chi might be the most significantly effective MBE intervention for mitigating depression among BC survivors. Healthcare professionals could consider recommending Liuzijue and Tai Chi as a complementary therapy for BC survivors who experience depression.

Degradation of malachite green by g-C3N4-modified magnetic attapulgite composites under visible-light conditions.

Water resources are seriously threatened by dye wastewater, and the removal of the dye molecules from the wastewater has garnered considerable interest. People have favored photocatalytic technology in recent years for the treatment of dye wastewater. In this work, attapulgite (ATP) was used as a carrier, Fe3O4 and g-C3N4 were grafted onto ATP, and the surface was then modified with polyethyleneimine (PEI) to produce photocatalyst ATP-Fe3O4-g-C3N4-PEI, which was used in Malachite green (MG) dye wastewater. The structure and surface properties of the composites were analyzed and characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray spectrum (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Uv-vis spectrum analysis, zeta potential measurement, and vibrating-sample magnetometry (VSM) analysis. The removal performance of ATP-Fe3O4-gC3N4-PEI for MG was studied, and the removal mechanism was explored and revealed. It has been shown that the heterojunction formed by Fe3O4 and g-C3N4 can inhibit the compounding of photogenerated electrons and holes, effectively improving the performance of the ATP-Fe3O4-g-C3N4-PEI. Electron paramagnetic resonance (EPR) analysis confirmed that ATP-Fe3O4-g-C3N4-PEI could generate hydroxyl radicals (·OH) and superoxide radicals (·O2-) to degrade the MG. It was believed that ATP-Fe3O4-g-C3N4-PEI could generate hydroxyl radicals (·OH) through the photocatalysis and the Fenton reaction of the composite materials. Under the action of H+, ·O2-, and ·OH, the removal rate of MG by ATP-Fe3O4-g-C3N4-PEI exceeded 98 % at an optimal condition. The intermediate products and degradation pathways of MG degradation were also inferred by LC-MS analysis. These results showed that the prepared photocatalyst has excellent degradation performance for MG and could be used in dye wastewater treatment.

ANKRD22 knockdown suppresses papillary thyroid cell carcinoma growth and migration and modulates the Wnt/ß-catenin signaling pathway.

The incidence of thyroid cancer is escalating globally, particularly among women. Studies have demonstrated the abnormal activation of Ankyrin Repeat Domain 22 (ANKRD22) in various cancers, but it remains uncertain whether it is also highly expressed in papillary thyroid carcinoma (PTC). Our objective was to evaluate the role of ANKRD22 in PTC. The expression of ANKRD22 varies among tissues, as validated by the Cancer Genome Atlas, and further predicted using the Tumor Immune Estimation Resource. Predicted results were examined via polymerase chain reaction and western blotting. Subsequently, the expression of ANKRD22 in cells was suppressed by RNA interference, and changes in cell progression were examined in conjunction with the cell counting kit-8 assay, transwell assay, and colony formation assay. Finally, the effects of ANKRD22 knockdown on the Epithelial-to-Mesenchymal transition and the Wnt/ß-catenin signaling pathway were investigated through western blotting. An in vivo mice model was established to validate the effect of ANKRD22. This study discovered that ANKRD22 was highly expressed in PTC, which was validated by polymerase chain reaction and western blotting. Knockdown of ANKRD22, significantly reduced thecell viability, colony formation capability, and cell invasion and migration abilities. Furthermore, we found that knockdown of ANKRD22 impaired both tumor Epithelial-to-Mesenchymal transition and the activation of the Wnt/ß-catenin signaling pathway. In conclusion, this study revealed that the knockdown of ANKRD22 inhibits the growth and migration of papillary thyroid cell carcinoma by regulating the Wnt/ß-catenin signaling pathway.

A Single-Event-Hardened Scheme for Ring Oscillator Applied to Radiation-Resistant PLL Microsystems.

A voltage-controlled oscillator (VCO) is one of the key modules of the phase-locked loop (PLL) microsystem, and it is easy to bombard using high-energy particles in a radiation environment, resulting in the single-event effect. In order to improve the anti-radiation ability of the PLL microsystems used in the aerospace environment, a new voltage-controlled oscillator hardened circuit is proposed in this work. The circuit consists of delay cells with an unbiased differential series voltage switch logic structure with a tail current transistor. By reducing sensitive nodes and using the positive feedback of the loop, the recovery process of the VCO circuit to the single-event transient (SET) is reduced and accelerated, so as to reduce the sensitivity of the circuit to the single-event effect. The simulation results based on the SMIC 130 nm complementary metal-oxide-semiconductor (CMOS) process show that the maximum phase shift difference of the PLL with the hardened VCO is reduced by 53.5%, which shows that the hardened VCO structure can reduce the sensitivity of the PLL to the SET and improve the reliability of the PLL in the radiation environment.

Synthesis of Si/C Composites by Silicon Waste Recycling and Carbon Coating for High-Capacity Lithium-Ion Storage.

It is of great significance to recycle the silicon (Si) kerf slurry waste from the photovoltaic (PV) industry. Si holds great promise as the anode material for Li-ion batteries (LIBs) due to its high theoretical capacity. However, the large volume expansion of Si during the electrochemical processes always leads to electrode collapse and a rapid decline in electrochemical performance. Herein, an effective carbon coating strategy is utilized to construct a precise Si@CPPy composite using cutting-waste silicon and polypyrrole (PPy). By optimizing the mass ratio of Si and carbon, the Si@CPPy composite can exhibit a high specific capacity and superior rate capability (1436 mAh g-1 at 0.1 A g-1 and 607 mAh g-1 at 1.0 A g-1). Moreover, the Si@CPPy composite also shows better cycling stability than the pristine prescreen silicon (PS-Si), as the carbon coating can effectively alleviate the volume expansion of Si during the lithiation/delithiation process. This work showcases a high-value utilization of PV silicon scraps, which helps to reduce resource waste and develop green energy storage.

SFPQ promotes the proliferation, migration and invasion of hepatocellular carcinoma cells and is associated with poor prognosis.

Liver cancer is a prevalent type of tumor worldwide. CRISPR-Cas9 technology can be utilized to identify therapeutic targets for novel therapeutic approaches. In this study, our goal was to identify key genes related to the survival of hepatocellular carcinoma (HCC) cells by analyzing the DepMap database based on CRISPR-Cas9. We screened candidate genes associated with HCC cell survival and proliferation from DepMap and identified their expression levels in HCC from the TCGA database. To develop a prognostic risk model based on these candidate genes, we performed WGCNA, functional pathway enrichment analysis, protein interaction network construction, and LASSO analysis. Our findings show that 692 genes were critical for HCC cell proliferation and survival, and among them, 571 DEGs were identified in HCC tissues. WGCNA categorized these 584 genes into three modules, and the blue module consisting of 135 genes was positively linked to the tumor stage. Using the MCODE approach in Cytoscape, we identified ten hub genes in the PPI network, and through Cox univariate analysis and Lasso analysis, we developed a prognostic model consisting of three genes (SFPQ, SSRP1, and KPNB1). Furthermore, knocking down SFPQ inhibited HCC cell proliferation, migration, and invasion. In conclusion, we identified three core genes (SFPQ, SSRP1, and KPNB1) that are essential for the proliferation and survival of HCC cells. These genes were used to develop a prognostic risk model, and knockdown of SFPQ was found to inhibit the proliferation, migration, and invasion of HCC cells.

Analysis of Metabolites and Metabolic Pathways of Three Chinese Jujube Cultivar.

Most studies on metabolites in jujube fruits focus on specific types of metabolites, but there are only a few comprehensive reports on the metabolites in jujube fruits. In order to understand the variance of metabolites in fruits of different jujube varieties. The objective of this study was to explore the metabolic components of jujube fruit by comparing three cultivars, namely Linyi LiZao (LZ), Jiaocheng SuantianZao (STZ), and Xianxian Muzao (MZ). The metabolites present in the fruits of these three cultivars were evaluated and compared. The results revealed the detection of 1059 metabolites across the three jujube varieties, with each cultivar exhibiting distinct metabolic characteristics. Notably, MZ exhibited a higher abundance of six metabolite classes, namely amino acids and derivatives, flavonoids, lipids, organic acids, phenolic acids, and terpenoids, compared to LZ. Conversely, LZ exhibited higher concentrations of alkaloids, lignans, coumarins, nucleotides, and their derivatives compared to the other two cultivars. In terms of STZ, its content of amino acids and derivatives, lignans and coumarins, organic acids, and phenolic acids was largely similar to that of LZ. However, the content of alkaloids, nucleotides, and their derivatives, and terpenoids was significantly higher in STZ compared to LZ. Additionally, STZ exhibited lower levels of flavonoids and lipids compared to LZ. Moreover, MZ was found to be less nutritionally rich than STZ, except for lignans and coumarins, as it displayed lower levels of all the metabolites. KEGG pathway enrichment analysis revealed six significantly different metabolic pathways (p < 0.05) between LZ and MZ, including arginine and proline metabolism, sphingolipid metabolism, flavonoid biosynthesis, glutathione metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. The metabolites in STZ and MZ exhibited three significantly different pathways (p < 0.05), primarily associated with flavonoid biosynthesis, arginine and proline metabolism, and sphingolipid metabolism. The significantly differential metabolites between LZ and STZ were observed in the phenylpropionic acid biosynthesis pathway and the ubiquinone and other terpenoid-quinone biosynthesis pathways. LZ showed a closer relationship with STZ than with MZ. STZ and LZ exhibited higher medicinal values, while LZ had lower acidity and MZ displayed better antioxidant activity. This study presents the first thorough analysis of metabolites in LZ, STZ, and MZ cultivars, which can serve as a theoretical basis for quality analysis, functional research, and classification processing of jujube fruit.

An Improved Blind Zone Channelization Structure and Rapid Implementation Method.

The paper proposes an enhanced design for broadband digital receivers that aims to improve signal capture probability, real-time performance, and the hardware development cycle. To overcome the issue of false signals in the blind zone channelization structure, this paper introduces an improved joint-decision channelization structure that reduces channel ambiguity during signal reception. Xilinx's high-level synthesis (HLS) tools are used for accelerated algorithm implementation, and techniques such as pipelining and loop parallelization are employed to reduce system latency. The entire system is implemented on FPGA. The simulation results demonstrate that the proposed solution effectively eliminates channel ambiguity, improves algorithm implementation speed, and meets the design requirements.

Polyphenols from Prunus mume: extraction, purification, and anticancer activity.

Prunus mume is an ancient medicinal herb and food that are commonly used in Asian countries with high nutritional ingredients and biological activities. Polyphenols are important functional components in Prunus mume. To obtain a more efficient extraction process of Prunus mume polyphenols, a single-factor test and response surface method were used. After extraction and purification, the final polyphenol content of Prunus mume (L1) was up to 90%. Biological experiments showed that L1 had high anticancer activity against HeLa (125.28 µg mL-1), HepG2 (117.24 µg mL-1), MCF-7 (170.19 µg mL-1), and A549 (121.78 µg mL-1) in vitro by MTT assay. The combination of DDP and DOX significantly enhanced the anticancer activity of the four cell lines, especially L1-DOX had the smallest IC50 value of 0.04 µg mL-1 against HepG2 cells, indicating the combination of drugs had synergistic effects. It is further demonstrated that L1 could inhibit cell proliferation by inducing apoptosis with ROS detection and confocal fluorescence images. The relative tumor proliferation rate (T/C) was 40.6%, and the tumor inhibition rate was 57.9%, indicating L1 to have no significant toxicity but high anti-HepG2 activity in vivo. Although the study is very limited, it is anticipated to provide a reference for further exploration of the functionality of the plant.

LncRNA CASC19 Enhances the Radioresistance of Nasopharyngeal Carcinoma by Regulating the miR-340-3p/FKBP5 Axis.

Radioresistance remains a serious obstacle encountered in the radiotherapy of nasopharyngeal carcinoma (NPC). Both mRNAs and non-coding RNAs (ncRNAs), including long ncRNA (lncRNA) and microRNA (miRNA), play essential roles in radiosensitivity. However, the comprehensive expression profiles and competing endogenous RNA (ceRNA) regulatory networks among lncRNAs, miRNAs, and mRNAs in NPC radioresistance are still bewildering. In this study, we performed an RNA-sequencing (RNA-seq) assay in the radioresistant NPC cells CNE2R and its parental cells CNE2 to identify the differentially expressed lncRNAs, miRNAs, and mRNAs. The ceRNA networks containing lncRNAs, miRNAs, and mRNAs were predicted on the basis of the Pearson correlation coefficients and authoritative miRanda databases. In accordance with bioinformatic analysis of the data of the tandem mass tag (TMT) assay of CNE2R and CNE2 cells and the gene chip assay of radioresistant NPC samples in pre- and post-radiotherapy, the radioresistance-related signaling network of lncRNA CASC19, miR-340-3p, and FKBP5 was screened and further verified using an RT-qPCR assay. CASC19 was positively associated with FKBP5 expression while negatively correlated with miR-340-3p, and the target binding sites of CASC19/miR-340-3p and miR-340-3p/FKBP5 were confirmed using a dual-luciferase reporter assay. Moreover, using an mRFP-GFP-LC3 maker, it was found that autophagy contributed to the radioresistance of NPC. MiR-340-3p inhibition or FKBP5 overexpression could rescue the suppression of autophagy and radioresistance induced by CASC19 knockdown in CNE2R cells. In conclusion, the CASC19/miR-340-3p/FKBP5 network may be instrumental in regulating NPC radioresistance by enhancing autophagy, which provides potential new therapeutic targets for NPC.

Occurrence and exposure risk assessment of organochlorine pesticides in two waterbird species from Honghu Lake Wetland, Central China.

Monitoring and evaluating bird exposure to hazardous pollutants in wetlands are receiving considerable attention. In this study, the occurrence of 18 organochlorine pesticides (OCPs) in the muscle of bean geese (Anser fabalis) and common teals (Anas crecca) collected from Honghu Lake Wetland (HLW), Central China was studied. Additionally, an exposure risk assessment model was applied to obtain risk levels of OCPs to these birds through three oral routes (food intake, water drinking and soil ingestion). The results suggested that the most abundant OCPs detected in the muscle of waterbirds were DDTs (7.68-602 ng/g lipid weight), followed by HCHs (1.39-89.8 ng/g lipid weight). A significant difference (p < 0.05) existed between two species, but most of OCPs exhibited no statistically relationship with age or gender (p > 0.05). The compositional patterns of OCPs combined with ratios of certain metabolites to their parent compounds indicated that all OCPs in the HLW were largely from historical usage except heptachlor. The exposure risk assessment revealed that common teals with lighter weight had greater exposure risks than bean geese. Of the OCPs analyzed, DDTs could probably cause harm to target birds studied here. Exposure via food intake was identified to be significant while soil ingestion and water drinking contributed least, but they should still be concerned.

SDC1-dependent TGM2 determines radiosensitivity in glioblastoma by coordinating EPG5-mediated fusion of autophagosomes with lysosomes.

Glioblastoma multiforme (GBM) is the most common brain malignancy insensitive to radiotherapy (RT). Although macroautophagy/autophagy was reported to be a fundamental factor prolonging the survival of tumors under radiotherapeutic stress, the autophagic biomarkers coordinated to radioresistance of GBM are still lacking in clinical practice. Here we established radioresistant GBM cells and identified their protein profiles using tandem mass tag (TMT) quantitative proteomic analysis. It was found that SDC1 and TGM2 proteins were overexpressed in radioresistant GBM cells and tissues and they contributed to the poor prognosis of RT. Knocking down SDC1 and TGM2 inhibited the fusion of autophagosomes with lysosomes and thus enhanced the radiosensitivity of GBM cells. After irradiation, TGM2 bound with SDC1 and transported it from the cell membrane to lysosomes, and then bound to LC3 through its two LC3-interacting regions (LIRs), coordinating the encounter between autophagosomes and lysosomes, which should be a prerequisite for lysosomal EPG5 to recognize LC3 and subsequently stabilize the STX17-SNAP29-VAMP8 QabcR SNARE complex assembly. Moreover, when combined with RT, cystamine dihydrochloride (a TGM2 inhibitor) extended the lifespan of GBM-bearing mice. Overall, our findings demonstrated the EPG5 tethering mode with SDC1 and TGM2 during the fusion of autophagosomes with lysosomes, providing new insights into the molecular mechanism and therapeutic target underlying radioresistant GBM.Abbreviations: BafA1: bafilomycin A1; CQ: chloroquine; Cys-D: cystamine dihydrochloride; EPG5: ectopic P-granules 5 autophagy tethering factor; GBM: glioblastoma multiforme; GFP: green fluorescent protein; LAMP2: lysosomal associated membrane protein 2; LIRs: LC3-interacting regions; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NC: negative control; RFP: red fluorescent protein; RT: radiotherapy; SDC1: syndecan 1; SNAP29: synaptosome associated protein 29; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TGM2: transglutaminase 2; TMT: tandem mass tag; VAMP8: vesicle associated membrane protein 8; WT: wild type.

Angiotensin II increases the firing activity of pallidal neurons and participates in motor control in rats.

The globus pallidus has emerged as a crucial node in the basal ganglia motor control circuit under both healthy and parkinsonian states. Previous studies have shown that angiotensin II (Ang II) and angiotensin subtype 1 receptor (AT1R) are closely related to Parkinson's disease (PD). Recent morphological study revealed the expression of AT1R in the globus pallidus of mice. To investigate the functions of Ang II/AT1R on the globus pallidus neurons of both normal and parkinsonian rats, electrophysiological recordings and behavioral tests were performed in the present study. Electrophysiological recordings showed that exogenous and endogenous Ang II mainly excited the globus pallidus neurons through AT1R. Behavioral tests further demonstrated that unilateral microinjection of Ang II into the globus pallidus induced significantly contralateral-biased swing in elevated body swing test (EBST), and bilateral microinjection of Ang II into the globus pallidus alleviated catalepsy and akinesia caused by haloperidol. AT1R was involved in Ang II-induced behavioral effects. Immunostaining showed that AT1R was expressed in the globus pallidus of rats. On the basis of the present findings, we concluded that pallidal Ang II/AT1R alleviated parkinsonian motor deficits through activating globus pallidus neurons, which will provide a rationale for further investigations into the potential of Ang II in the treatment of motor disorders originating from the basal ganglia.