Self-assembly formation of Co quantum dot loaded N-doped porous carbon cathode for quinoline degradation in the electro-Fenton system.

Quinoline is high toxicity and difficult biodegradation in oil washing wastewater. Therefore, efficient removal of quinoline contaminant from water bodies poses a major challenge. Hence, Co quantum dot loaded N-doped porous carbon (CoNC) nanosheets grown in situ on carbon cloth were fabricated as cathode for the degradation of quinoline in electro-Fenton system. Under optimal conditions (c(Fe2+) = 0.5 mM, U = -0.3 V, pH = 3), quinoline was completely degraded within 15 min with superior apparent rate constant of 0.385 min-1, which was 19.6 times higher than that of the ZIF-L precursor, due to the abundance of Co QDs active sites and hydrophilicity and electrical conductivity of N-doped porous carbon. In addition, three reaction pathways for quinoline were deduced by combining Density Functional Theory (DFT) calculation and Liquid Chromatography-Mass Spectrometry (LC-MS). More importantly, in situ FTIR and free energy calculations were analyzed to reveal that pathway Ⅰ as spontaneous reaction was the main reaction pathway. Finally, the toxicity of the intermediates was assessed with ECOSAR software and E. coli experiments, and the overall toxicity decreased during the degradation reactions. This work provides novel perspectives on environmental protection by designing in-situ grown cathodes through self-assembly method, thereby effectively purifying pollutants from wastewater.

Unlocking the anticancer activity of gambogic acid: a shift towards ferroptosis via a GSH/Trx dual antioxidant system.

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in ferroptosis by regulating the cellular antioxidant response and maintaining redox balance. However, compounds that induce ferroptosis through dual antioxidant pathways based on Nrf2 have not been fully explored. In our study, we investigated the impact of Gambogic acid (GA) on MCF-7 cells and HepG2 cells in vitro. The cytotoxicity, colony formation assay and cell cycle assay demonstrated potent tumor-killing ability of GA, while its effect was rescued by ferroptosis inhibitors. Furthermore, RNA sequencing revealed the enrichment of ferroptosis pathway mediated by GA. In terms of ferroptosis indicators detection, evidences for GA were provided including reactive oxygen species (ROS) accumulation, alteration in mitochondrial membrane potential (MMP), disappearance of mitochondrial cristae, lipid peroxidation induction, malondialdehyde (MDA) accumulation promotion, iron ion accumulation as well as glutathione (GSH)/thioredoxin (Trx) depletion. Notably, Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) successfully rescued GA-induced MDA accumulation. In terms of mechanism, Nrf2 was found to play a pivotal role in GA-induced ferroptosis by inducing protein alterations through the iron metabolism pathway and GSH/Trx dual antioxidant pathway. Furthermore, GA exerted good antitumor activity in vivo through GSH/Trx dual antioxidant pathway, and Fer-1 significantly attenuated its efficacy. In conclusion, our findings first provided new evidence for GA as an inducer of ferroptosis, and Nrf2-mediated GSH/Trx dual antioxidant system played an important role in GA-induced ferroptosis.

Arthroscopic debridement improves range of motion for heterotopic ossification after total knee replacement: a retrospective cohort study.

The presence of heterotopic ossification (HO) after primary total knee replacement (TKR) is rare and associated with limited mobility and stiffness of the knee. This study aimed to identify if the arthroscopic debridement after TKR could decrease HO and improve the function and range of motion. Thirty HO patients after TKR were retrospectively separated into 2 cohorts. 15 patients of group A accepted the arthroscopic debridement, while 15 patients of group B only had non-operative treatment, mainly including oral nonsteroidal anti-inflammatory drugs (NSAIDs) and rehabilitative treatment. Visual analog scale (VAS) scores, knee society knee scores (KSS), range of motion (knee flexion and knee extension) were obtained before treatment and at 1 month, 3 months, and 6 months after treatment. Radiography of after-treatment was also evaluated to assess the changes in HO. There were 3 males and 27 females with a mean age of 67.4 ± 0.8 years in group A and 68.2 ± 1.3 in group B. The onset time of HO was 3-6 months. The maximum size of the ossification was < 2 cm in 23 knees, 2 cm < heterotopic bone < 5 cm in 6 knees and > 5 cm in 1 knee. The size of HO decreased gradually in all knees by X-ray film at the last follow-up. There were no significant differences in VAS scores after replacement between two groups (p > 0.05). The average range of motion preoperatively in group A was - 15.2-90.6°, which postoperatively increased to - 4.2-110.0°. Meanwhile, the KSS scores and average range of motion of the group A were better than those of the group B at each follow-up time after treatment. Arthroscopic debridement can decrease HO seen from postoperative X-rays, improve the function and range of motion, as well as the pain remission between two groups are comparable. Consequently, arthroscopic resection of HO after TKR is recommended as soon as there is aggravating joint stiffness.

Helicobacter pylori upregulates circPGD and promotes development of gastric cancer.

PURPOSE: Helicobacter pylori (H. pylori) has unique biochemical traits and pathogenic mechanisms, which make it a substantial cause of gastrointestinal cancers. Circular RNAs (circRNAs) have concurrently been identified as an important participating factor in the pathophysiology of several different cancers. However, the underlying processes and putative interactions between H. pylori and circRNAs have received very little attention. To address this issue, we explored the interaction between H. pylori and circRNAs to investigate how they might jointly contribute to the occurrence and development of gastric cancer. METHODS: Changes in circPGD expression in H. pylori were detected using qRT-PCR. Cell proliferation and migration changes were assayed by colony formation, the CCK-8 assay and the transwell assay. Apoptosis was measured by flow cytometry. Western blot was conducted to detect changes in cell migration, apoptosis, proliferation and inflammation-associated proteins. QRT-PCR was used to measure changes in circPGD and inflammation-associated factors. RESULTS: We found that H. pylori induced increased circPGD expression in infected human cells and facilitated gastric cancer progression in three ways by promoting cell proliferation and migration, enhancing the inflammatory response, and inhibiting apoptosis. CONCLUSIONS: CircPGD appears to play a role in H. pylori-related gastric cancer and may thus be a viable, novel target for therapeutic intervention.

Effect of Gut Microbiota-Mediated Tryptophan Metabolism on Inflammaging in Frailty and Sarcopenia.

Frailty syndrome refers to the nonspecific state of increased body vulnerability and decreased antistress and recovery abilities after stress during aging. Sarcopenia is the major component of frailty and is characterized by the gradual loss of muscle mass, strength, and function with age. Inflammaging is the gradual increase in inflammatory status during aging, and it disrupts immune tolerance, causes physiological changes in tissues, organs, and normal cells, and is related to frailty and sarcopenia. The gut microbiota is an extremely complex and diverse microbial community that coevolves with the host. The composition and structure of the gut microbiota and the metabolism of tryptophan (Trp) significantly change in older adults with frailty and sarcopenia. The gut microbiota participates in regulating the Trp metabolic pathways of kynurenine (Kyn), 5-hydroxytryptamine (5-HT), and indole in the gastrointestinal tract. The Trp metabolites derived from the gut microbiota may synergistically promote the occurrence of age-related frailty and sarcopenia by promoting inflammation in the intestines, nervous system, and muscles. The role and mechanisms of the gut microbiota, Trp metabolism, and inflammaging in age-related frailty and sarcopenia may be a worthwhile research direction to help promote healthy aging.

Transcriptomic and physiological analysis of atractylodes chinensis in response to drought stress reveals the putative genes related to sesquiterpenoid biosynthesis.

BACKGROUND: Atractylodes chinensis (DC) Koidz., a dicotyledonous and hypogeal germination species, is an important medicinal plant because its rhizome is enriched in sesquiterpenes. The development and production of A. chinensis are negatively affected by drought stress, especially at the seedling stage. Understanding the molecular mechanism of A. chinensis drought stress response plays an important role in ensuring medicinal plant production and quality. In this study, A. chinensis seedlings were subjected to drought stress treatment for 0 (control), 3 (D3), and 9 days (D9). For the control, the sample was watered every two days and collected on the second morning after watering. The integration of physiological and transcriptomic analyses was carried out to investigate the effects of drought stress on A. chinensis seedlings and to reveal the molecular mechanism of its drought stress response. RESULTS: The malondialdehyde, proline, soluble sugar, and crude protein contents and antioxidative enzyme (superoxide dismutase, peroxidase, and catalase) activity were significantly increased under drought stress compared with the control. Transcriptomic analysis indicated a total of 215,665 unigenes with an average length of 759.09 bp and an N50 of 1140 bp. A total of 29,449 differentially expressed genes (DEGs) were detected between the control and D3, and 14,538 DEGs were detected between the control and D9. Under drought stress, terpenoid backbone biosynthesis had the highest number of unigenes in the metabolism of terpenoids and polyketides. To identify candidate genes involved in the sesquiterpenoid and triterpenoid biosynthetic pathways, we observed 22 unigene-encoding enzymes in the terpenoid backbone biosynthetic pathway and 15 unigene-encoding enzymes in the sesquiterpenoid and triterpenoid biosynthetic pathways under drought stress. CONCLUSION: Our study provides transcriptome profiles and candidate genes involved in sesquiterpenoid and triterpenoid biosynthesis in A. chinensis in response to drought stress. Our results improve our understanding of how drought stress might affect sesquiterpenoid and triterpenoid biosynthetic pathways in A. chinensis.

Excess Mortality for Femoral Intertrochanteric Fracture Patients Aged 50 Years and Older Treated Surgically and Conservatively in Tianjin, China: A Cohort Study.

OBJECTIVE: Intertrochanteric fracture is one type of hip fracture, which is the most serious consequence of osteoporosis. Along with the growing elderly population, intertrochanteric fracture is expected to rise increasingly. The aim of this study was to assess excess mortality after intertrochanteric fractures and to identify the predictors of long-term mortality by therapy among patients aged 50 years and older in Tianjin. METHODS: This is a retrospective cohort study on mortality for 3029 patients aged 50 years and older in Tianjin experiencing an intertrochanteric fracture between December 26, 2014 and December 31, 2018. Data were from Tianjin Hospital Hip Fracture (THHF) cohort. Follow-up period was until March 31, 2022. Mortality, excess mortality, and comorbidities were analyzed and stratified by therapy and gender. Time dependent Cox models were performed to estimate the effects of the variables. RESULTS: Absolute mortality for all the patients was 5.90% at 3 months, 12.55% at 12 months, 19.92% at 24 months and 27.28% at 36 months. Absolute mortality for surgical group was 1.57% at 3 months, 4.77% at 12 months, 8.49% at 24 months and 12.07% at 36 months, significantly lower than conservative group: 10.50% at 3 months, 20.73% at 12 months, 31.96% at 24 months and 43.04% at 36 months. We found a substantially lower mortality (hazard ratio [HR] 0.34, 95% confidence internal, [CI]: 0.23-0.52, p = 0.000) among patients undergoing surgical therapy than those undergoing conservative therapy, even when controlled for gender, age, the length of hospital stay, and all the comorbidities. Female patients (HR 0.68, 95% CI: 0.58-0.79, p = 0.000) were less likely to die than male patients after an intertrochanteric fracture. Patients treated by the two methods were both found to have excess mortality rates compared to the general population, although in different levels. The excess mortality rates for patients in the conservative therapy group were 14.46% in males and 17.93% in females, while in the surgical therapy group, 2.78% in females and 4.37% in males. The comorbidities moderate or severe renal disease (HR 2.19, 95% CI: 1.61-2.98, p = 0.000), metastatic solid tumor (HR 6.35, 95% CI: 1.56-25.85, p = 0.010), hypoproteinemia (HR 1.22, 95% CI: 1.01-1.47, p = 0.034), and older age (HR 1.89, 95% CI: 1.73-2.08, p = 0.000) were also risk factors on mortality. A worse-case analysis for the primary outcome were performed as sensitivity analysis and it was consistent with the original conclusion. CONCLUSION: Intertrochanteric factures for people aged 50 years older were found to have excess mortality compared to the general population in Tianjin city, and preventing the fractures in the hip for elderly people was imperative. After controlling tfor comorbidities and age, female gender and surgical therapy were protective factors for the death after fractures, which could provide strong evidence for patients and surgeons to make decisions.

AsHC 360 Exposure Influence on Epileptiform Discharges in Hippocampus of Infantile Male Rats In Vitro.

Arsenic-containing hydrocarbons (AsHCs) are typical arsenolipids found in various marine organisms. They can penetrate the blood-brain barrier, specifically affecting synaptic plasticity and the learning and memory ability of hippocampal neurons. Temporal lobe epilepsy often occurs in the hippocampus. Thus, the possible influence of AsHCs exposure to temporal lobe epilepsy garnered attention. The present study investigated the effects of epileptiform discharges (EDs) signals introduced by low-magnesium ACSF in the hippocampus of infantile male rats in vitro, using electrophysiological techniques with multi-electrode arrays under AsHC 360 exposure. In our study of the effects of AsHC 360 on EDs signals, we found that inter-ictal discharges (IIDs) were not significantly impacted. When AsHC 360 was removed, any minor effects observed were reversed. However, when we examined the impact of AsHC 360 on ictal discharges (IDs), distinct patterns emerged based on the concentration levels. For low-concentration groups (5, 20, 60 µg As L-1), both the frequency and duration effects on IDs returned to normal post-elimination of AsHC 360. However, this recovery was not evident for concentrations of 100 µg As L-1 or higher. IDs were only observed in EDs signals during exposures to AsHC 360 concentrations up to 60 µg As L-1. In these conditions, ID frequencies significantly enhanced with the increased of AsHC 360 concentration. At high concentrations of AsHC 360 (≥100 µg As L-1), the transition from IIDs or pre-ictal discharges (PIDs) to IDs was notably inhibited. Additional study on co-exposure of AsHC 360 (100 µg As L-1) and agonist (10 nM (S)-(-)-Bay-K-8644) indicated that the regulation of EDs signals under AsHC 360 exposure could be due to directly interference with the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) expression which influences the binding of excitatory glutamate neurotransmitter to AMPAR. The results suggest that EDs activities in the hippocampus of infantile Sprague Dawley rats are concentration-dependent on AsHC 360 exposure. Thus, it provides a basis for the seafood intake with AsHCs for epileptic patients and those with potential seizures.

A non-inferiority study to compare the effect of silica gel fiber dressing with alginate dressing on healing of venous leg ulcers.

BACKGROUND: Silica gel fiber (SGF) dressing is a novel patch for wound healing. OBJECTIVE: To compare the efficacy and safety of SGF dressing with alginate dressing in local treatment of venous leg ulcers. METHODS: Patients with venous leg ulcers who had undergone effective treatment of venous hypertension and debridement were randomized to receive wound care with either SGF dressing or alginate dressing for 4 weeks. Wounds were assessed weekly during the first 4 weeks and then every 2 weeks until the 8th week. The primary endpoint was the efficacy rate. Secondary endpoints included ulcer area reduction rate, healing rate, frequency of dressing changes, pain score, patient satisfaction, and treatment-related adverse events. RESULTS: A total of 130 patients were enrolled, 67 treated with SGF and 63 with alginate dressing, and the efficacy rates were 89.6% (SGF group) and 84.1% (alginate group). SGF induced a higher "no pain" rate than alginate at week 2 (61.4% vs 43.5%) and week 3 (67.6% vs 53.1%), and a higher "highly satisfied" rate at week 4 (83.3% vs 78.8%) and week 8 (75% vs 59.1%). Markedly fewer dressing changes were required in the SGF group. CONCLUSIONS: SGF dressing is non-inferior to alginate dressing in treating venous leg ulcers. It even substantially decreased the frequency of dressing changes when compared with alginate dressing.

Prognostic biomarkers for sepsis mortality based on the literature and LC-MS-based metabolomics of sepsis patients.

OBJECTIVES: The management of sepsis, a potentially lethal overreaction to infection, is limited by the lack of prognostic tools to guide its treatment. Our aim is to identify a novel metabolic biomarker panel for predicting sepsis mortality based on a literature review and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. METHODS: In the literature, we found metabolomics biomarkers reported to predict sepsis mortality. We determined the classifications, reported frequency, and KEGG pathway enrichment of these markers. Using serum samples from 20 sepsis survivors and 20 non-survivors within 28 days after admission to the intensive care unit (ICU), we performed LC-MS-based metabolomics. Based on the literature review and metabolomics, a prognostic biomarker panel for sepsis was identified and its area under the curve (AUC) values was assessed. RESULTS: Kynurenate, caffeine, and lysoPC 22:4 were selected as a prognostic biomarker panel for sepsis. The panel had an area under the curve (AUC) of 0.885 (95% CI, 0.694-1) evaluated by linear support vector machine (SVM) and 0.849 (0.699-1) by random forest (RF), which was higher than that of the Sequential Organ Failure Assessment (SOFA). A combination of kynurenate, caffeine, and lysoPC 22:4 and SOFA provided the best discriminating performance, with AUCs of 0.961 (0.878-1) for SVM and 0.916 (0.774-1) for RF. CONCLUSIONS: The prognostic biomarker panel consisting of kynurenate, caffeine, and lysoPC 22:4 may aid in the identification of sepsis patients at a high risk of death, leading to personalized therapy in clinical practice that will improve sepsis survival.

CircRNA_15430 reduced by Helicobacter pylori infection and suppressed gastric cancer progression via miR-382-5p/ZCCHC14 axis.

BACKGROUND: Helicobacter pylori (H.pylori, HP) is one of the main causes of gastric cancer (GC). CircRNAs have been reported to play a crucial role in developing many types of cancer. However, the role of circRNAs in the development and progression of HP infected-GC has not been studied. METHODS: The location of circRNA_15430 in GC cells were detected by nuclear and cytoplasmic RNA fractionation and RNA fluorescence in situ hybridization analysis (FISH) assays, and circRNA_15430, miR-382-5p and ZCCHC14 expression in GC cell lines and tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The function of circRNA_15430 in GC cells were examined by using colony formation, cell counting kit-8 (CCK-8) and Transwell assays, flow cytometry and laser scanning confocal microscopy. The protein levels were detected by Western blotting. Whether circRNA_15430 sponges miR-382-5p was monitored with a dual-luciferase reporter assay. Furthermore, circRNA_15430 was analyzed in vivo in tumor growth with nude mice. RESULTS: CircRNA_15430 is primarily localized in the cytoplasm of GC cells, and downregulated in the GC cell lines and tissues, and is negatively correlated with the tumor size. Downregulation of circRNA_15430 promotes proliferation, migration and suppresses cell apoptosis and autophagy in GC cells. Mechanically, circRNA_15430 acts as a miR-382-5p sponge, alleviating the inhibitory effect of miR-382-5p on its target ZCCHC14. Knockdown circRNA_15430 enhances tumor growth in vivo. In addition, circRNA_15430 was reduced in HP + gastritis tissues and HP-infected MGC-803 cells, reversing the pro-HP effect on autophagy. Additionally, miR-382-5p was increased in HP + gastritis tissue and HP-infected MGC-803 cells while ZCCHC14 decreased in HP-infected MGC-803 cells. MiR-382-5p reverses the effect of si-ZCCHC14 on autophagosome numbers in MGC-803 cells. CONCLUSIONS: Therefore, circRNA_15430 plays an inhibitory role in GC and regulates the progression of HP infection-related GC, providing a novel molecular marker for GC therapy.

Low Expression of GIGYF1 Inhibits Metastasis, Proliferation, and Promotes Apoptosis and Autophagy of Gastric Cancer Cells.

GRB10 interacting GYF protein 1 (GIGYF1) binds to the N-terminal region of Grb10, regulates multiple signaling pathways. However, it is not clear what happens to cell proliferation, metastasis, apoptosis, and autophagy when the expression level of GIGYF1 gene is reduced. Detection of GIGYF1 expression in clinical tissue specimens and gastric cancer (GC) cell lines by quantitative Real-time PCR (qRT-PCR), GIGYF1 gene was knocked down in MGC-803 cells using small interfering RNA, the effect of GIGYF1 gene on cell metastasis was detected using Transwell assay and wound healing assay, the effect on cell proliferation was detected using plate cloning assay and cck-8 assay, the effect on apoptosis was detected using flow cytometry, autophagosomes were detected using laser confocal microscopy, and the effect on protein expression was detected using immunofluorescence and Western blotting. GIGYF1 gene expression was higher in tumor tissue samples than in paracancer tissue samples, and higher in human GC cell lines than in human normal gastric epithelial cells. GIGYF1 gene knockdown inhibited cell migration, scratch healing ability and EMT process, weakened cell proliferation ability, increased apoptosis rate, promoted the formation of autophagosomes, and changed the corresponding protein expression level. Meanwhile, GIGYF1 knockdowns inhibited the ERK and AKT signaling. In conclusion, the low expression of GIGYF1 gene can inhibit the occurrence and progression of gastric cancer, during which the ERK and AKT signaling pathways are inhibited.

Relationship between inferior mesenteric artery diameter and rectal cancer.

Introduction: A dilated inferior mesenteric vein has been reported in rectal cancer patients. However, no study has yet reported inferior mesenteric artery (IMA) enlargement in rectal cancer. We aimed to assess the relationship between the IMA diameter and rectal cancer. Material and methods: Patients diagnosed with rectal cancer and a control group of 42 patients in our hospital from July 2017 to June 2019 were evaluated. The IMA diameter was independently measured by two observers on axial computed tomography images. Results: The mean IMA diameter was wider in rectal cancer patients (2.49 ±0.53 mm) than in the control group (2.20 ±0.47 mm, p < 0.001). The IMA diameter of patients with stage I, stage II, stage III, and stage IV cancers was 2.24 ±0.36 mm, 2.45 ±0.39 mm, 2.80 ±0.55 mm, and 2.85 ±0.51 mm, respectively (p < 0.001). The IMA diameter correlated positively and moderately with TNM stage (r = 0.519, p < 0.001). The IMA diameter of patients with T1, T2, T3, and T4 tumors was 2.18 ±0.31 mm, 2.39 ±0.50 mm, 2.55 ±0.48 mm, and 2.73 ±0.51 mm, respectively (p < 0.001). The IMA diameter also correlated positively and moderately with T stage (r = 0.457, p < 0.001). The IMA diameter of patients with N0, N1, and N2 tumors was 2.37 ±0.39 mm, 2.83 ±0.60 mm, and 2.71 ±0.40 mm, respectively (p < 0.001); however, the IMA diameter did not correlate with N stage (r = 0.166, p = 0.077). Patients with M1 tumors had a wider IMA diameter than patients with M0 tumors (p = 0.011). Conclusions: The IMA in rectal cancer patients enlarges as the TNM stage gets higher. The IMA diameter can be accepted as a possibly important marker for the staging of rectal cancer.

Holes on surfaces of the weathered plastic fragments from coastal beaches.

The surface morphology of weathered plastics undergoes a variety of changes. In this study, 3950 plastic fragments from 26 beaches around the world, were assessed to identify holes. Holes were identified on 123 fragments on 20 beaches, with the highest frequency (10.3 %) being identified at Qesm AL Gomrok Beach in Egypt. The distribution of holes could be divided into even, single-sided, and random types. The external and internal holes were similar in size (37 ± 15 µm) of even type fragments. The external holes were larger than the internal holes in single-sided (516 ± 259 µm and 383 ± 161 µm) and random (588 ± 262 µm and 454 ± 210 µm) fragment types. The external hole sizes were positively correlated with the internal hole sizes for each type. This study reports a novel deformation phenomenon on the surface of weathered plastics and highlights their potential effects on plastics.

Probiotic-fermented Portulaca oleracea L. alleviated DNFB-induced atopic dermatitis by inhibiting the NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Probiotic fermentation is a mild and safe biological method to boost the performance of herbs. Portulaca oleracea L. (PO), with folklore records of purgative, anti-dermatological and anti-epidemic effects, has been demonstrated to possess anti-inflammatory, immunomodulatory, and antioxidant properties. However, the potential of PO for the treatment of atopic dermatitis (AD) has not been sufficiently explored. AIM OF STUDY: This study aimed to evaluate the therapeutic benefits of PO and fermented Portulaca oleracea L. (FPO) and explore their intrinsic mechanisms. METHODS: By utilizing 2,4-dinitrofluorobenzene-induced AD mice as a model, the histopathology of the lesions was observed using H&E and toluidine blue staining methods; the levels of immunoglobulin E (Ig E), histamine (HIS), and thymic stromal lymphopoietin (TSLP) in serum were measured using ELISA, whereas, the expression of inflammatory cytokines in skin lesion was measured using ELISA and immunohistochemistry experiments. The expression of tumor necrosis factor-α (TNF-α), IKKα, NF-κB mRNA was measured using qPCR; and the expression of TNF-α、p-IKKα, p-IκBα, p-NF-κB was measured using western blotting. RESULTS: Both 20 mg/mL PO and FPO alleviated mast cell infiltration and lesion pathology, reduced serum levels of Ig E, HIS and TSLP, down-regulated the expression of AD-related inflammatory cytokines, such as, TNF-α, interferon-γ, and interleukin-4, and increased filaggrin expression. Furthermore, they inhibited the expression of TNF-α, IKKα, and NF-κB genes and TNF-α, p-IKKα, p-NF-κB and p-IκBα proteins associated with the NF-κB signaling pathway. CONCLUSIONS: PO and FPO has a positive therapeutic potential on AD, indicating that it may be employed as alternative therapies for AD.

Characterization and distribution of polybrominated diphenyl ethers in shellfish in Shenzhen coastal waters and assessment of human health risks.

This study aims to investigate the profiles of polybrominated diphenyl ethers (PBDEs) in shellfish obtained from Shenzhen coastal waters and assess the potential health risks. We analyzed 74 shellfish samples from eight different species for PBDEs (BDE-28, -47, -99, -100, -153, -154, -183, -209). The concentrations of total PBDEs in different shellfish species ranged from 2.02 to 360.17 pg g-1 wet weight, with the highest levels found in Pectinidae, Babylonia areolate, Ostreidae, Perna viridis, Haliotis diversicolor, Corbiculidae, Pinctada margaritifera, and Veneridae in descending order. Among the PBDE congeners analyzed, BDE-47 was the most abundant, followed by BDE-154 and BDE-153. Furthermore, the estimated daily intake of PBDEs through shellfish consumption for Shenzhen residents were between 0.11 and 0.19 ng kg-1(bw) day-1. To our knowledge, this is the first study to systematically investigate the profiles of PBDEs in eight different shellfish species from Shenzhen's coastal waters and evaluate the potential human health risks associated with shellfish consumption.

Case Report: Identification of a novel NTRK3-AJUBA fusion co-existing with ETV6-NTRK3 fusion in papillary thyroid carcinoma.

NTRK fusions are validated oncogenic drivers of various adult and pediatric tumor types, including thyroid cancer, and serve as a therapeutic target. Recently, tropomyosin receptor kinase (TRK) inhibitors, such as entrectinib and larotrectinib, display promising therapeutic efficacy in NTRK-positive solid tumors. Although some NTRK fusion partners have been identified in thyroid cancer, the spectrum of NTRK fusion is not fully characterized. In this study, a dual NTRK3 fusion was identified by targeted RNA-Seq in a 47-year-old female patient with papillary thyroid carcinoma. The patient harbors a novel in-frame fusion between NTRK3 exon 13 and AJUBA exon 2, co-existing with a known in-frame fusion between ETV6 exon 4 and NTRK3 exon 14. The dual NTRK3 fusion was validated by Sanger sequencing and fluorescence in situ hybridization (FISH) but lack TRK protein expression as defined by pan-TRK immunohistochemistry (IHC). We supposed the pan-TRK IHC result to be falsely negative. In conclusion, we present the first case of a novel NTRK3-AJUBA fusion co-existing with a known ETV6-NTRK3 fusion in thyroid cancer. These findings extend the spectrum of translocation partners in NTRK3 fusion, and the effect of dual NTRK3 fusion on TRK inhibitor therapy and prognosis needs long-term follow-up.

Changes in intracellular calcium concentration level accompany age-related inhibitions of long-term potentiation in hippocampus induced by extremely low frequency electromagnetic fields.

Extremely low frequency electromagnetic fields (ELF-EMFs) have received increasing attention and in-depth research due to their ability to affect learning and memory functions. However, its regulation and intrinsic mechanism at different ages in early developmental stages remains unclear. In this article, the regulation of 15 Hz/2 mT ELF-EMFs on long-term potentiation (LTP) persistence in the hippocampal CA1 region of Sprague-Dawley (SD) rats at early developmental stages (8-, 15-, 22-, and 29-day-old) are investigated by electrophysiological techniques. The results show that ELF-EMFs differentially inhibit LTP persistence due to age difference, and the younger the age, the more significant the inhibitory effect. Second, the inhibitory effect of ELF-EMFs on LTP persistence disappeared after the addition of 2-aminoethoxydiphenyl borate (2-APB) to block inositol-1,4,5-trisphosphate receptors (IP3 Rs) localized to intracellular calcium stores to reduce the intracellular calcium concentration ([Ca2+ ]i ), proving that the LTP persistence regulated by ELF-EMFs is associated with the IP3 Rs-mediated intracellular calcium stores. Finally, the level of [Ca2+ ]i was intervened by adjusting the extracellular calcium concentration([Ca2+ ]e ). Interestingly, the inhibitory effect of ELF-EMFs on LTP persistence in the 15-day-old group disappeared by increasing [Ca2+ ]e , whereas the inhibitory effect of ELF-EMFs on LTP persistence in the 29-day-old group appeared by decreasing [Ca2+ ]e . Our findings reveal the underlying mechanism of the effect of ELF-EMFs on synaptic plasticity in hippocampal CA1 area at early developmental stages and provide new insights into more rational application and protection of ELF-EMFs.

Peripheral blood T-lymphocyte subsets are potential biomarkers of disease severity and clinical outcomes in patients with ulcerative colitis: a retrospective study.

BACKGROUND: Ulcerative colitis (UC) is considered an immune-mediated disease. The disorder of T-lymphocyte subsets plays an important role in the pathogenesis of UC. The aim of this study was to evaluate the significance of peripheral blood T-lymphocyte subsets in assessing disease severity and predicting clinical outcomes in UC patients. METHODS: The retrospective case-control study was performed in 116 UC patients with active disease and 90 healthy controls (HC). The UC patients included were followed up for 180 days. Analyses of t-test, Spearman's correlation coefficient, multivariable Cox regression analysis, receiver operating characteristic (ROC) curves and cumulative survival analysis were done. RESULTS: The UC patients had lower proportions of CD4+T cells (42.85%±9.77% vs 45.71%±7.94%, P=0.021) and higher proportion of CD8+T cells (27.88%±8.86% vs 25.00%±6.47%, P=0.008) than HC. The severely active UC patients had higher proportion of CD3+HLA-DR+ T cells (8.83%±6.55% vs 2.80%±1.55%, P<0.001; 8.83%±6.55% vs 4.06%±5.01%, P<0.001) and CD8+T cells (31.35%±8.49% vs 26.98%±7.98%, P=0.029; 31.35%±8.49% vs 25.46%±9.15%, P=0.003) than mild and moderate group, whereas lower proportion of CD4+CD25+T cells (2.86%±1.35% vs 3.46%±1.07%, P=0.034) than mild group and CD4+T cells (40.40%±9.36% vs 44.73%±10.39%, P=0.049) than moderate group. The area under the curve (AUC) of CD3+HLA-DR+ T cells for assessing severely active UC was 0.885, with the cut-off value of 5.33%. The sensitivity was 76.32% and specificity was 89.74%. The combination of CD3+HLA-DR+ T cells and CRP had stronger assessment value with AUC of 0.929. The AUC of CD8+T cells, CD4+/CD8+ ratio and CD4+CD25+T cells for assessing disease severity was 0.677, 0.669 and 0.631 respectively. Within the 180 days follow-up, 24 patients (20.69%) had UC-related readmission or surgery, with higher proportion of CD3+HLA-DR+ T cells (10.66%±9.52% vs 3.88%±2.56%, P=0.003) and CD8+T cells (31.19%±10.59% vs 27.01%±8.20%, P=0.039) than those without readmission and surgery. The proportion of CD3+HLA-DR+ T cells was the independent predictor of UC-related readmission or surgery (HR=1.109, P=0.002). The AUC of CD3+HLA-DR+ T cells for predicting readmission or surgery was 0.796 with the cut-off value of 5.38%. UC patients with CD3+HLA-DR+T cells proportion>5.38% had a shorter time to readmission or surgery (log-rank test, P<0.001). CONCLUSIONS: The combination of CD3+HLA-DR+T cells and CRP may be potential biomarker of disease severity in UC patients. The high proportion of CD3+HLA-DR+T cells may be associated with an increased risk of readmission or surgery in UC patients.

Modulatory effects of real-time electromagnetic stimulation on epileptiform activity in juvenile rat hippocampus based on multi-electrode array recordings.

Electromagnetic stimulation (EMS) has proven to be useful for the focal suppression of epileptiform activity (EFA) in the hippocampus. There is a critical period during EFA for achieving the transition from brief interictal discharges (IIDs) to prolonged ictal discharges (IDs), and it is unknown whether EMS can modulate this transition. Therefore, this study aimed to evaluate the intensity- and time-dependent effect of EMS on the transition of EFA. A juvenile rat EFA model was constructed by perfusing magnesium-free artificial cerebrospinal fluid (aCSF) on brain slices, and the induced EFA was recorded using a micro-electrode array (MEA) platform. After a stable EFA event was recorded for some time, real-time pulsed magnetic stimulation with low and high peak-to-peak input magnetic field intensities was carried out. A 5-min intervention with real-time magnetic fields with low intensity was found to reduce the amplitude of IDs (ID events still existed), whereas a 5-min intervention with real-time magnetic fields with high input voltages completely suppressed IDs. Short-time magnetic fields (9 s and 1 min) with high or low input intensity had no effect on EFA. Real-time magnetic fields can block the normal EFA process from IIDs to IDs (i.e., a complete EFA cycle) and this suppression effect is dependent on input intensities and intervention duration. The experimental findings further indicate that magnetic stimulation may be chosen as an alternative antiepileptic therapy.