Human amnion mesenchymal stem cells promote endometrial repair via paracrine, preferentially than transdifferentiation.

BACKGROUND: Intrauterine adhesion (IUA) is one of the most severe causes of infertility in women of childbearing age with injured endometrium secondary to uterine performance. Stem cell therapy is effective in treating damaged endometrium. The current reports mainly focus on the therapeutic effects of stem cells through paracrine or transdifferentiation, respectively. This study investigates whether paracrine or transdifferentiation occurs preferentially in treating IUA. METHODS: Human amniotic mesenchymal stem cells (hAMSCs) and transformed human endometrial stromal cells (THESCs) induced by transforming growth factor beta (TGF-ß1) were co-cultured in vitro. The mRNA and protein expression levels of Fibronectin (FN), Collagen I, Cytokeratin19 (CK19), E-cadherin (E-cad) and Vimentin were detected by Quantitative real-time polymerase chain reaction (qPCR), Western blotting (WB) and Immunohistochemical staining (IHC). The Sprague-Dawley (SD) rats were used to establish the IUA model. hAMSCs, hAMSCs-conditional medium (hAMSCs-CM), and GFP-labeled hAMSCs were injected into intrauterine, respectively. The fibrotic area of the endometrium was evaluated by Masson staining. The number of endometrium glands was detected by hematoxylin and eosin (H&E). GFP-labeled hAMSCs were traced by immunofluorescence (IF). hAMSCs, combined with PPCNg (hAMSCs/PPCNg), were injected into the vagina, which was compared with intrauterine injection. RESULTS: qPCR and WB revealed that FN and Collagen I levels in IUA-THESCs decreased significantly after co-culturing with hAMSCs. Moreover, CK19, E-cad, and Vimentin expressions in hAMSCs showed no significant difference after co-culture for 2 days. 6 days after co-culture, CK19, E-cad and Vimentin expressions in hAMSCs were significantly changed. Histological assays showed increased endometrial glands and a remarkable decrease in the fibrotic area in the hAMSCs and hAMSCs-CM groups. However, these changes were not statistically different between the two groups. In vivo, fluorescence imaging revealed that GFP-hAMSCs were localized in the endometrial stroma and gradually underwent apoptosis. The effect of hAMSCs by vaginal injection was comparable to that by intrauterine injection assessed by H&E staining, MASSON staining and IHC. CONCLUSIONS: Our data demonstrated that hAMSCs promoted endometrial repair via paracrine, preferentially than transdifferentiation.

IUA is the crucial cause of infertility in women of childbearing age, and no satisfactory treatment measures have been found in the clinic. hAMSCs can effectively treat intrauterine adhesions through paracrine and transdifferentiation mechanisms. This study confirmed in vitro and in vivo that amniotic mesenchymal stem cells preferentially inhibited endometrial fibrosis and promoted epithelial repair through paracrine, thus effectively treating intrauterine adhesions. The level of fibrosis marker proteins in IUA-THESCs decreased significantly after co-culturing with hAMSCs for 2 days in vitro. However, the level of epithelial marker proteins in hAMSCs increased significantly, requiring at least 6 days of co-culture. hAMSCs-CM had the same efficacy as hAMSCs in inhibiting fibrosis and promoting endometrial repair in IUA rats, supporting the idea that hAMSCs promoted endometrial remodeling through paracrine in vivo. In addition, GFP-labeled hAMSCs continuously colonized the endometrial stroma instead of the epithelium and gradually underwent apoptosis. These findings prove that hAMSCs ameliorate endometrial fibrosis of IUA via paracrine, preferentially than transdifferentiation, providing the latest insights into the precision treatment of IUA with hAMSCs and a theoretical basis for promoting the "cell-free therapy" of MSCs.

Ecotoxicological effects of polyethylene microplastics and lead (Pb) on the biomass, activity, and community diversity of soil microbes.

Microplastics and heavy metals are ubiquitous and persistent contaminants that are widely distributed worldwide, yet little is known about the effects of their interaction on soil ecosystems. A soil incubation experiment was conducted to investigate the individual and combined effects of polyethylene microplastics (PE-MPs) and lead (Pb) on soil enzymatic activities, microbial biomass, respiration rate, and community diversity. The results indicate that the presence of PE-MPs notably reduced soil pH and elevated soil Pb bioavailability, potentially exacerbated the combined toxicity on the biogeochemical cycles of soil nutrients, microbial biomass carbon and nitrogen, and the activities of soil urease, sucrase, and alkaline phosphatase. Soil CO2 emissions increased by 7.9% with PE-MPs alone, decreased by 46.3% with single Pb, and reduced by 69.4% with PE-MPs and Pb co-exposure, compared to uncontaminated soils. Specifically, the presence of PE-MPs and Pb, individually and in combination, facilitated the soil metabolic quotient, leading to reduced microbial metabolic efficiency. Moreover, the addition of Pb and PE-MPs modified the composition of the microbial community, leading to the enrichment of specific taxa. Tax4Fun analysis showed the effects of Pb, PE-MPs and their combination on the biogeochemical processes and ecological functions of microbes were mainly by altering amino acid metabolism, carbohydrate metabolism, membrane transport, and signal transduction. These findings offer valuable insights into the ecotoxicological effects of combined PE-MPs and Pb on soil microbial dynamics, reveals key assembly mechanisms and environmental drivers, and highlights the potential threat of MPs and heavy metals to the multifunctionality of soil ecosystems.

Effects of silencing hsa_circ_0015326 on proliferation, migration, invasion, and apoptosis of epithelial ovarian cancer cells.

Although the treatment of ovarian cancer has made great progress, there are still many patients who are not timely detected and given targeted therapy due to unknown pathogenesis. Recent studies have found that hsa_circ_0015326 is upregulated in ovarian cancer and is involved in the proliferation, invasion, and migration of ovarian cancer cells. However, whether hsa_circ_0015326 can be used as a new target of ovarian cancer needs further investigation. Therefore, the effect of hsa_circ_0015326 on epithelial ovarian cancer was investigated in this study. At first, si-hsa_circ_0015326 lentivirus was transfected into epithelial ovarian cancer cells. Then real-time fluorescence quantitative PCR (qRT-PCR) was used to detect hsa_circ_0015326 level. The proliferation of ovarian cancer cells was detected by CCK-8 assay. The horizontal and vertical migration abilities of the cells were detected by wound-healing assay and Transwell assay, respectively. Transwell assay was also used to determine the invasion rate. As for the apoptosis rate, it was assessed by flow cytometry. As a result, the expression level of hsa_circ_0015326 in A2780 and SKOV3 was found to be higher than that in IOSE-80. However, after transfecting si-hsa_circ_0015326 and si-NC into the cells, the proliferation, migration, and invasion abilities of A2780 and SKOV3 cells in the si-hsa_circ_0015326 group were significantly reduced in comparison to those in the si-NC and mock groups, while their apoptosis rates were elevated. Collectively, silencing hsa_circ_0015326 bears the capability of inhibiting the proliferation, migration, and invasion of ovarian cancer cells while increasing apoptosis rate. It can be concluded that hsa_circ_0015326 promotes the malignant biological activities of epithelial ovarian cancer cells.

Association Between Helicobacter pylori and Laryngopharyngeal Reflux Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: It is controversial that Helicobacter pylori (H pylori) is involved in the pathogenesis or development of laryngopharyngeal reflux disease (LPRD). OBJECTIVE: To investigate the potential association between LPRD and H pylori infection. MATERIAL AND METHODS: A systematic review was performed of studies assessing the diagnosis or treatment of LPRD among patients with H pylori infection. Data sources are PubMed/MEDLINE, EMBASE[Ovid], Cochrane Library, and Web of Science, and ClinicalTrials.gov. RESULTS: Fifteen studies were analyzed in the review, with all eligible for the meta-analysis. A significant association between H pylori infection and LPRD was detected for higher rates of H pylori infection in patients with LPRD than in non-LPRD patients (relative risk (RR), 1.35; 95% CI, 1.12-1.63; P = 0.002), and H pylori-positive patients had a higher prevalence of LPRD than H pylori-negative patients (RR, 1.19; 95% CI, 1.07-1.31; P = 0.001). The prevalence of H pylori among patients with LPRD was 49% (95% CI, 36-61), the prevalence of H pylori among patients with non-LPRD was 35% (95% CI, 23-49). CONCLUSION AND SIGNIFICANCE: The limited evidence indicated the association between LPRD risk and increased H pylori infection. Different population races, diagnostic approach to LPRD, variant H pylori testing methods, age and sex may contribute to the heterogeneity. Further well-designed studies regarding the efficacy of H pylori eradication in the treatment of LPRD are strongly recommended in the future.

The adaptor protein ECAP, the co-repressor LEUNIG, and the transcription factor BEH3 interact and regulate microsporocyte generation in Arabidopsis.

Histo-specification and morphogenesis of anthers during development in Arabidopsis (Arabidopsis thaliana) are well understood. However, the regulatory mechanism of microsporocyte generation at the pre-meiotic stage remains unclear, especially how archesporial cells are specified and differentiate into two cell lineages with distinct developmental fates. SPOROCYTELESS (SPL) is a key reproductive gene that is activated during early anther development and remains active. In this study, we demonstrated that the EAR motif-containing adaptor protein (ECAP) interacts with the Gro/Tup1 family co-repressor LEUNIG (LUG) and the BES1/BZR1 HOMOLOG3 (BEH3) transcription factor to form a transcription activator complex, epigenetically regulating SPL transcription. SPL participates in microsporocyte generation by modulating the specification of archesporial cells and the archesporial cell-derived differentiation of somatic and reproductive cell layers. This study illustrates the regulation of SPL expression by the ECAP-LUG-BEH3 complex, which is essential for the generation of microsporocytes. Moreover, our findings identified ECAP as a key transcription regulator that can combine with different partners to regulate gene expression in distinct ways, thereby facilitating diverse processes in various aspects of plant development.

The Discharge Behavior and Mechanism of Polyimide Aerogel under Electron Irradiation.

The response and mechanism of polyimide aerogel under electron irradiations were investigated. The experimental results indicated that electron irradiation could not damage the skeleton polyimide in the aerogel due to its high stability, but could result in a discharge within. The morphology of the discharge shows some dendritic discharge patterns, and the material surrounding the discharge channels was carbonized. The numerical simulation results indicated that the incident electrons, and also large amount induced secondary electrons, would be deposited inhomogeneously within the nano-porous polyimide aerogel. This would result in forming an ultra-high electrical potential of up to about 8.5 × 1010 V/m (which is far higher than the breakdown strength (2 × 108 V/m) of bulk polyimide materials) in a local region. This may be the leading cause of the obvious discharge in the materials. Furthermore, it was found that the actual reason for the discharge is related to the residual gas within the nano-porous structure; namely, the more internal residual gas (as a shorter-time vacuum pumping in the irradiated chamber), the more serious the discharge phenomenon. Correspondingly, the phenomenon may largely consist of both residual-gas discharge and surface flashover due to ultra-high local potentials induced by unevenly deposited charges in the porous aerogel.

Cepharanthine maintains integrity of the blood-brain barrier (BBB) in stroke via the VEGF/VEGFR2/ZO-1 signaling pathway.

Dysfunction of tight junctions such as zonula occludens protein-1 (ZO-1)-associated aggravation of blood-brain barrier (BBB) permeability plays an important role in the progression of stroke. Cepharanthine (CEP) is an extract from the plant Stephania cepharantha. However, the effects of CEP on stroke and BBB dysfunction have not been previously reported. In this study, we report that CEP improved dysfunction in neurological behavior in a middle cerebral artery occlusion (MCAO) mouse model. Importantly, CEP suppressed blood-brain barrier (BBB) hyperpermeability by increasing the expression of ZO-1. Notably, we found that CEP inhibited the expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) in the cortex of MCAO mice. Additionally, the results of in vitro experiments demonstrate that treatment with CEP ameliorated cytotoxicity of human bEnd.3 brain microvascular endothelial cells against hypoxia/reperfusion (H/R). Also, CEP attenuated H/R-induced aggravation of endothelial permeability in bEND.3 cells by restoring the expression of ZO-1. Further study proved that the protective effects of CEP are mediated by inhibition of VEGF-A and VEGFR2. Based on the results, we conclude that CEP might possess a therapeutic prospect in stroke through protecting the integrity of the BBB mediated by the VEGF/VEGFR2/ZO-1 axis.

Jasmonate signaling pathway confers salt tolerance through a NUCLEAR FACTOR-Y trimeric transcription factor complex in Arabidopsis.

Jasmonate (JA) is a well-known phytohormone essential for plant response to biotic stress. Recently, a crucial role of JA signaling in salt resistance has been highlighted; however, the specific regulatory mechanism remains largely unknown. In this study, we found that the NUCLEAR FACTOR-Y (NF-Y) subunits NF-YA1, NF-YB2, and NF-YC9 form a trimeric complex that positively regulates the expression of salinity-responsive genes, whereas JASMONATE-ZIM DOMAIN protein 8 (JAZ8) directly interacts with three subunits and acts as the key repressor to suppress both the assembly of the NF-YA1-YB2-YC9 trimeric complex and the transcriptional activation activity of the complex. When plants encounter high salinity, JA levels are elevated and perceived by the CORONATINE INSENSITIVE (COI) 1 receptor, leading to the degradation of JAZ8 via the 26S proteasome pathway, thereby releasing the activity of the NF-YA1-YB2-YC9 complex, initiating the activation of salinity-responsive genes, such as MYB75, and thus enhancing the salinity tolerance of plants.

Isolation and antioxidant activity of peptides from Chinese hairy tofu.

Hairy tofu is a famous Chinese snack that is made from soybeans and rich in various nutrients. In order to further explore the antioxidant peptides of hairy tofu hydrolysates, seven proteases were used to hydrolyze hairy tofu. The results of in vitro radical scavenging activity showed that hairy tofu hydrolysates obtained by pancreatin exhibited the highest antioxidant activity. After Sephadex G-25 gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC), 97 peptides were identified in the most antioxidant fraction using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, nine peptides were synthesized and their antioxidant activities were assessed using a H2O2-induced oxidative 293T cell model. Finally, four peptides (QCESHK, LAWNEGR, NLQGENEWDQK, and FTEMWR) at concentrations of < 50 µg/ml significantly decreased the malondialdehyde content compared with the model group, displaying in vivo antioxidant activity and low cytotoxicity. Overall, this research provided the choice of using hairy tofu peptides as antioxidant products in the pharmaceutical and food industries.

Label-free colorimetric detection platform based on catalytic hairpin self-assembly and G-quadruplex/hemin DNAzyme for comprehensive biomarker profiling.

The expression level of human apurinic/apyrimidinic endonuclease 1 (APE1) is closely associated with the onset of various diseases, establishing it as a crucial clinical biomarker and a target in anti-cancer efforts. This study accomplished colorimetric and visual detection of APE1 by harnessing its endonuclease activity through catalytic hairpin self-assembly (CHA) and G-quadruplex/hemin DNAzyme. Optimization of the freedom degrees of the G-rich sequence significantly improved the detection performance of the strategy by influencing DNAzyme formation. Additionally, we replaced the signal reporting system with a molecular beacon to develop a fluorescence detection strategy, which served as an extension of the signal amplification system for validation and signal readout. The fluorescent probe method achieved a detection limit of 3.37 × 10-4 U/mL, while the colorimetric method yielded a detection limit of 6.5 × 10-3 U/mL, with a linear range spanning from 0.01 to 0.25 U/mL. Subsequently, the colorimetric approach effectively assessed APE1 activity in biological samples and facilitated the screening of APE1 activity inhibitors. Furthermore, this CHA/G-quadruplex/hemin DNAzyme strategy was adapted for the colorimetric detection of adenosine, showcasing its broad applicability across various biomarkers. The developed colorimetric analytical strategy represents a pivotal biosensing platform for diagnosing and treating diseases.

Migration of phosphorus in pig manure during pyrolysis process and slow-release mechanism of biochar in hydroponic application.

Pyrolysis is an effective method for treating of livestock and poultry manure developed in recent years. It can completely decompose pathogens and antibiotics, stabilize heavy metals, and enrich phosphorus (P) in biochar. To elucidate the P migration mechanism under different pig manure pyrolysis temperatures, sequential fractionation, solution 31P nuclear magnetic resonance, X-ray photoelectron spectroscopy, X-ray diffraction, and K-edge X-ray absorption near-edge structure techniques were used to analyze the P species in pig manure biochar (PMB). The results indicated that most of the organic P in the pig manure was converted to inorganic P during pyrolysis. Moreover, the transformation to different P groups pathways was clarified. The phase transition from amorphous to crystalline calcium phosphate was promoted when the temperature was above 600 °C. The content of P extracted by hydrochloric acid, which was the long-term available P for plant uptake, increased significantly. PMB pyrolyzed at 600 °C can be used as a highly effective substitute for P source. It provides the necessary P species (e.g. water-soluble P.) and metal elements for the growth of water spinach plants, and which are slow-release comparing with the Hogland nutrient solution.

AMPpred-MFA: An Interpretable Antimicrobial Peptide Predictor with a Stacking Architecture, Multiple Features, and Multihead Attention.

Antimicrobial peptides (AMPs) are small molecular polypeptides that can be widely used in the prevention and treatment of microbial infections. Although many computational models have been proposed to help identify AMPs, a high-performance and interpretable model is still lacking. In this study, new benchmark data sets are collected and processed, and a stacking deep architecture named AMPpred-MFA is carefully designed to discover and identify AMPs. Multiple features and a multihead attention mechanism are utilized on the basis of a bidirectional long short-term memory (LSTM) network and a convolutional neural network (CNN). The effectiveness of AMPpred-MFA is verified through five independent tests conducted in batches. Experimental results show that AMPpred-MFA achieves a state-of-the-art performance. The visualization interpretability analyses and ablation experiments offer a further understanding of the model behavior and performance, validating the importance of our feature representation and stacking architecture, especially the multihead attention mechanism. Therefore, AMPpred-MFA can be considered a reliable and efficient approach to understanding and predicting AMPs.

Treatment with adult glottic stenosis using CO2 laser surgery combined with self-made laryngeal dilator.

BACKGROUND/AIMS/OBJECTIVES: To investigate the treatment for adult glottic stenosis using CO2 laser surgery combined with a self-made laryngeal dilator. MATERIAL AND METHODS: A retrospective analysis was performed on 18 patients with glottic stenosis who were treated using CO2 laser surgery combined with a self-made laryngeal dilator in our hospital from January 2018 to December 2020. RESULTS: 4 cases were caused by trauma and one by laryngophthisis. Laryngeal stenosis occurred in 4 and 9 patients respectively after CO2 laser surgery and open partial laryngectomy. Of them, one patient underwent postoperative radiotherapy. All patients were treated through CO2 laser surgery combined with a self-made laryngeal dilator under general anesthesia. 3-6 months later, the dilator was removed. Inflammation, ulceration and granulation were observed surrounding the dilator. But these complications would be cured and respiration was not affected. Finally, four patients could not be extubated and the decannulation rate achieved 78%. All patients successfully decannulated could normally intake. 13 cases had good voice quality and only one patient pronounced hoarsely. CONCLUSIONS AND SIGNIFICANCE: It is demonstrated that the application of CO2 laser surgery combined with a laryngeal self-made dilator is feasible and effective for the treatment with adult glottic stenosis.

Environmental Stimuli and Phytohormones in Anthocyanin Biosynthesis: A Comprehensive Review.

Anthocyanin accumulation in plants plays important roles in plant growth and development, as well as the response to environmental stresses. Anthocyanins have antioxidant properties and play an important role in maintaining the reactive oxygen species (ROS) homeostasis in plant cells. Furthermore, anthocyanins also act as a "sunscreen", reducing the damage caused by ultraviolet radiation under high-light conditions. The biosynthesis of anthocyanin in plants is mainly regulated by an MYB-bHLH-WD40 (MBW) complex. In recent years, many new regulators in different signals involved in anthocyanin biosynthesis were identified. This review focuses on the regulation network mediated by different environmental factors (such as light, salinity, drought, and cold stresses) and phytohormones (such as jasmonate, abscisic acid, salicylic acid, ethylene, brassinosteroid, strigolactone, cytokinin, and auxin). We also discuss the potential application value of anthocyanin in agriculture, horticulture, and the food industry.

Arabidopsis MYB21 Negatively Regulates KTN1 to Fine-Tune the Filament Elongation.

The growth process of the stamen filament is crucial for plant reproduction. However, the molecular mechanisms underlying the regulation of filament growth remain largely unclear. Our study has identified that MYB21 is involved in the regulation of filament growth in Arabidopsis. In comparison to the wild type, the cell length of the filaments is notably reduced in the myb21 mutant. Moreover, we found that KTN1, which encodes a microtubule-severing enzyme, is significantly upregulated in the myb21 mutant. Additionally, yeast one-hybrid assays demonstrated that MYB21 can bind to the promoter region of KTN1, suggesting that MYB21 might directly regulate the expression of KTN1. Finally, transcriptional activity experiments showed that MYB21 is capable of suppressing the driving activity of the KTN1 promoter. This study indicates that the MYB21-KTN1 module may play a precise regulatory role in the growth of Arabidopsis filament cells.

Gas therapy strategies for depression and schizophrenia: A review.

Depression and schizophrenia are 2 serious mental disorders. Their effective treatment is an urgent medical and social problem at present. Drug treatment is the basic measure to improve mental disorders, especially serious mental disorders. However, the side effects of traditional antipsychotic drugs cannot be avoided. Surprisingly, in recent years, it has been found that nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S) and hydrogen (H2) can regulate corresponding signal pathways to treat mental diseases in animal models. More importantly, as gas signal molecules, they will not bring toxicity and side effects after metabolism. Therefore, in this review, we analyzed the effects of gas on depression and schizophrenia through endogenous gas generation and external gas delivery strategies in some animal models. Endogenous gas generation strategy: summarized the therapeutic mechanism of gas signaling molecules on depression and schizophrenia, and listed the main ways to inhibit or stimulate gas generation. External gas delivery strategy: The common external stimuli-responsive gasotransmitter prodrugs and some study of these prodrugs in the treatment of depression and schizophrenia are summarized. We also analyzed the prospects of nano-gas carrier in the treatment of depression and schizophrenia. Through this review, we hope to provide guidance for treating depression and schizophrenia by regulating relevant gas signal pathways, and provide reference for developing safe and effective drugs for treating mental disorders by summarizing exogenous gas drugs.

Spatial distribution and influencing factors of China's household biogas: evidence from provincial-level data.

To address the adjustment of the Chinese agricultural industry and to better promote the development of Chinese household biogas, this article summarizes and analyzes the spatial distribution characteristics and influencing factors of the type and number of biogas digesters, biogas production, biogas fermentation materials, and methods of fermentation residue utilization and ecological agriculture with household biogas by compiling a dataset covering 31 provincial administrative regions in China. The results show that hydraulic biogas digesters are distributed mainly in northwestern and northeastern China; in addition, continuously stirred biogas digesters and bottom-discharging biogas digesters are distributed mainly in southern and northern China, respectively. Because of temperature and population, the Sichuan and Henan Provinces have the highest number of biogas digesters and biogas production. The type of biogas fermentation materials depends on the local raw materials. Biogas slurry and residue are widely used as fertilizers; furthermore, biogas slurry is used for seed soaking in northeastern and southern China, and biogas residue is used as feed in central southern and northern China. The "Three-in-one" and "Four-in-one" biogas ecological models are used mostly in southern and northern China, respectively, and both are mainly affected by temperature. Finally, we propose various problems and countermeasures to enhance the development of the household biogas industry in China. Our findings are critical for China's policymakers to adopt effective measures for promoting the development of cleaner energy and the layout of the agricultural industry.

Chemical modification of curcumin increases its potency against hypopharyngeal carcinoma.

Hypopharyngeal carcinoma is notorious for its poor prognosis among all head and neck cancers, posing a persistent challenge in clinical settings. The continuous hyperactivation of the NFκB signalling pathway has been noted in various cancer types, including hypopharyngeal carcinoma. In our quest to develop a novel drug that targets hypopharyngeal cancer via the NFκB pathway, we employed curcumin, a well-known lead compound, and performed chemical modifications to create a mono-carbonyl analogue called L42H17. This compound exhibited exceptional stability and displayed an enhanced binding affinity to myeloid differentiation protein 2 (MD2). Consistent with expectations, L42H17 demonstrated the ability to inhibit TNF-α-induced phosphorylation of inhibitor of κB (IκB) kinase (IKK), prevent IκB degradation, and subsequently impede NFκB-p65 nuclear translocation in hypopharyngeal cancer cells. Additionally, L42H17 exhibited a remarkable capacity to induce cell cycle arrest at the G2-M phase by inactivating the cdc2-cyclin B1 complex. Moreover, it facilitated cell apoptosis by reducing Bcl-2 levels and augmenting the expression of cle-PARP and cle-caspase3. Importantly, we observed a significant enhancement in the anti-cancer efficacy of L42H17 in a patient-derived tumour xenograft (PDTX) model of hypopharyngeal carcinoma. In conclusion, our findings strongly suggest that L42H17 holds promise as a potential candidate drug for the treatment of hypopharyngeal carcinoma in the future.

Simultaneous photothermal and photocatalytic MOF- derived C/TiO2 composites for high-efficiency solar driven purification of sewage.

Solar-driven water evaporation is a promising technology of freshwater production to address the water scarcity. However, the photothermal material and the distilled water would be contaminated in the evaporation of wastewater including organic pollutants. In this work, MOF-derived C/TiO2 composites (carbonized UiO-66-NH2 (Ti)) with simultaneous photothermal and photocatalytic functions are designed for producing freshwater from sewage. With advantageous features of porous structure with large specific area, excellent sunlight absorption and super-hydrophilicity, the carbonized UiO-66-NH2 (Ti) layer exhibits high water evaporation efficiency of 94% under 1.0 sun irradiation. Meanwhile, the layer can simultaneously decompose the organic pollutants with degradation efficiency of 92.7% in the underlying water during solar-driven water evaporation. This bifunctional material will provide a new approach for solar-driven water evaporation and photocatalytic degradation of organic pollutant synergistically.

The potential role of GSK-3ß signaling pathway for amelioration actions of ketamine on the PTSD rodent model.

RATIONALE: Post-traumatic stress disorder (PTSD) is a complex, chronic psychiatric disorder typically triggered by life-threatening events and, as yet, lacks a specialized pharmacological treatment. The potential therapeutic role of ketamine, an N-methyl-D-aspartate receptor antagonist, in mitigating PTSD has been the subject of investigation. OBJECTIVE: The aim of this study was to elucidate alterations in the glycogen synthase kinase-3ß (GSK-3ß) signaling pathway in response to ketamine intervention, using the single prolonged stress (SPS) model of PTSD at a molecular level. METHODS: PTSD-like symptoms were simulated using the SPS model. Ketamine (10 mg/kg) and GSK-3ß antagonist SB216763 (5 mg/kg) were then administered intraperitoneally. Stress-related behavior was evaluated through the open field test (OFT) and the elevated plus maze test (EMPT). Additionally, brain activity was analyzed using quantitative electroencephalography (qEEG). Changes in protein and mRNA expressions of glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF), GSK-3ß, phosphorylated ser-9 GSK-3ß (p-GSK-3ß), FK506 binding protein 5 (FKBP5), and corticotropin-releasing hormone (CRH) were assessed in the hypothalamus via western blot and qPCR. RESULTS: SPS-exposed rats exhibited reduced distance and time spent in the center of the open arms, a pattern divergent from control rats. qEEG readings revealed SPS-induced increases in alpha power, low gamma and high gamma power. Furthermore, SPS triggered an upregulation in the protein and gene expression of GSK-3ß, GR, BDNF, p-GSK-3ß, and FKBP5, and downregulated CRH expression in the hypothalamus. Ketamine administration following the SPS procedure counteracted these changes by increasing the time spent in the center of the OFT, the distance traversed in the open arms of the EMPT, and mitigating SPS-induced alterations in cerebral cortex oscillations. Moreover, ketamine reduced the protein levels of GSK-3ß, GR, p-GSK-3ß, and altered the ratio of p-GSK-3ß to GSK-3ß. Gene expression of GSK-3ß, GR, BDNF, and FKBP5 decreased in the SPS-Ket group compared to the SPS-Sal group. CONCLUSIONS: Ketamine appeared to remediate the abnormal GSK-3ß signaling pathway induced by SPS. These findings collectively suggest that ketamine could be a promising therapeutic agent for PTSD symptoms, working through the modulation of the GSK-3ß signaling pathway.