Polystyrene Microplastics Induce Injury to the Vascular Endothelial Through NLRP3-Mediated Pyroptosis.

The health risks associated with microplastics have attracted widespread attention. Polystyrene microplastics (PS-MPs) can induce damage to cardiac tissue, while pyroptosis-mediated injury to the vascular endothelial plays a vital role in the pathogenesis of cardiovascular diseases. The study intended to explore the role and mechanism of NLR family pyrin domain containing 3 (NLRP3) mediated pyroptosis in PS-MPs causing the injury of vascular endothelial cells. In vivo, Wistar rats were exposed to 0.5, 5, and 50 mg/kg/d 0.5 µm PS-MPs. In vitro, the human vascular endothelial cells (HUVECs) were used for mechanistic studies. siRNA was used for silencing the NILRP3 gene. H&E staining and flow cytometry were performed to examine the vascular injury and cell membrane damage. The oxidative stress was detected by flow cytometry, immunofluorescence, and corresponding kits. ELISA were used to measure the levels of inflammatory factors. Real-time PCR and western blot were used to measure the expression of pyroptosis signaling pathway. In rats, PS-MPs could cause vascular damage, oxidative stress, and inflammatory response, and activated the pyroptosis signaling pathway. HUVECs exposure to PS-MPs, the vitality decreased in a dose-dependent manner, ROS and MDA were significantly increased while SOD was decreased. PS-MPs induced the onset of pyroptosis signaling pathway in HUVECs. Cell membrane damage and the levels of IL-Iß and IL-18 in HUVECs significantly increased, those are symbols for the development of pyroptosis. Inhibition of NLRP3-mediated pyroptosis effectively protected HUVECs from PS-MPs-induced damage. Pyroptosis played a vital role in controlling the vascular endothelial injury caused by PS-MPs.

Filamentous bacteria-induced sludge bulking can alter antibiotic resistance gene profiles and increase potential risks in wastewater treatment systems.

Sludge bulking caused by filamentous bacteria is a prevalent issue in wastewater treatment systems. While previous studies have primarily concentrated on controlling sludge bulking, the biological risks associated with it have been overlooked. This study demonstrates that excessive growth of filamentous bacteria during sludge bulking can significantly increase the abundance of antibiotic resistance genes (ARGs) in activated sludge. Through metagenomic analysis, we identified specific ARGs carried by filamentous bacteria, such as Sphaerotilus and Thiothrix, which are responsible for bulking. Additionally, by examining over 1,000 filamentous bacterial genomes, we discovered a diverse array of ARGs across different filamentous bacteria derived from wastewater treatment systems. Our findings indicate that 74.84% of the filamentous bacteria harbor at least one ARG, with the occurrence frequency of ARGs in these bacteria being approximately 1.5 times higher than that in the overall bacterial population in activated sludge. Furthermore, genomic and metagenomic analyses have shown that the ARGs in filamentous bacteria are closely linked to mobile genetic elements and are frequently found in potentially pathogenic bacteria, highlighting potential risks posed by these filamentous bacteria. These insights enhance our understanding of ARGs in activated sludge and underscore the importance of risk management in wastewater treatment systems.

Efficacy and safety of aspirin in venous thromboembolism prevention after total hip arthroplasty, total knee arthroplasty or fracture.

Background: This study aims to analyse the efficacy and safety of aspirin in the prevention of venous thromboembolism (VTE) for patients undergoing total hip arthroplasty (THA), total knee arthroplasty (TKA) or fracture. Patients and methods: Two independent investigators searched PubMed, Embase, Cochrane and ClinicalTrials.gov from January 2000 to June 2023 to retrieve randomized control trials (RCTs) about aspirin in VTE prevention after arthroplasty or fracture. Then, the relative risk (RR) was utilized to evaluate its efficiency and safety. Results: A total of 16 RCTs with 27,864 patients were included. There was no statistical difference in the incidence of deep-vein thrombosis (RR: 1.31, p = 0.100), pulmonary embolism (RR:1.05, p = 0.850), VTE (RR:1.28, p = 0.290), major bleeding (RR:0.96, p = 0.900), and death (RR:1.01, p = 0.960) between the aspirin group and the anticoagulants group. Subgroup analysis showed that a relatively higher incidence of deep-vein thrombosis in patients undergoing TKA (RR:1.49, p = 0.030), fracture (RR:1.48, p = 0.001), patients receiving 81 mg aspirin twice daily (RR:1.48, p = 0.001) and patients from North America (RR:1.57, p<0.001) when comparing aspirin with anticoagulants. Meanwhile, the incidence of VTE was higher in patients receiving 100 mg aspirin once daily (RR:1.82, p<0.001) compared with anticoagulants. Additionally, the incidence of all bleeding (RR:2.00, p = 0.030) was higher in patients receiving aspirin in Asia compared with anticoagulants. Conclusions: In terms of clinical effectiveness and safety, aspirin (antiplatelet agent) was generally not inferior to anticoagulants in the prevention of VTE after THA, TKA, or fracture. Notably, the clinical effectiveness of aspirin was affected by different surgical types, the doses of aspirin and races.

Hyperactivation of mTOR/eIF4E Signaling Pathway Promotes the Production of Tryptophan-To-Phenylalanine Substitutants in EBV-Positive Gastric Cancer.

Although messenger RNA translation is tightly regulated to preserve protein synthesis and cellular homeostasis, chronic exposure to interferon-γ (IFN-γ) in several cancers can lead to tryptophan (Trp) shortage via the indoleamine-2,3-dioxygenase (IDO)- kynurenine pathway and therefore promotes the production of aberrant peptides by ribosomal frameshifting and tryptophan-to-phenylalanine (W>F) codon reassignment events (substitutants) specifically at Trp codons. However, the effect of Trp depletion on the generation of aberrant peptides by ribosomal mistranslation in gastric cancer (GC) is still obscure. Here, it is shows that the abundant infiltrating lymphocytes in EBV-positive GC continuously secreted IFN-γ, upregulated IDO1 expression, leading to Trp shortage and the induction of W>F substitutants. Intriguingly, the production of W>F substitutants in EBV-positive GC is linked to antigen presentation and the activation of the mTOR/eIF4E signaling pathway. Inhibiting either the mTOR/eIF4E pathway or EIF4E expression counteracted the production and antigen presentation of W>F substitutants. Thus, the mTOR/eIF4E pathway exposed the vulnerability of gastric cancer by accelerating the production of aberrant peptides and boosting immune activation through W>F substitutant events. This work proposes that EBV-positive GC patients with mTOR/eIF4E hyperactivation may benefit from anti-tumor immunotherapy.

Sinensetin Inhibits Angiogenesis in Lung Adenocarcinoma via the miR-374c-5p/VEGF-A/VEGFR-2/AKT Axis.

Sinensetin is a product isolated from Orthosiphon aristatus, and its antitumor activities have been well established. This study focused on the role and mechanism of sinensetin in lung adenocarcinoma (LUAD). LUAD cells were treated with various concentrations of sinensetin. The proliferation, migration, invasion, and angiogenesis of LUAD cells were detected using colony formation, transwell, and tube formation assays, respectively. The protein levels of VEGF-A, VEGFR-2, and phosphorylated AKT (ser473) were measured by western blotting. The targeted relationship between VEGF-A and miR-374c-5p was verified by luciferase reporter assay. BALB/c nude mice inoculated with A549 cells were treated with sinensetin (40 mg/kg/day) by gavage for 21 days to investigate the effect of sinensetin on tumor growth and angiogenesis in vivo. We found that sinensetin reduced proliferation, migration, invasion, angiogenesis, and cancer stem characteristics of LUAD cells. Sinensetin also suppressed LUAD tumor growth and angiogenesis in vivo. Sinensetin downregulated VEGF-A expression in LUAD cells by enhancing miR-374c-5p expression. MiR-374c-5p inhibited the VEGF-A/VEGFR-2/AKT pathway in LUAD cells. The antitumor effect of sinensetin was reversed by overexpression of VEGF-A or inhibition of miR-374c-5p. Overall, sinensetin upregulates miR-374c-5p to inhibit the VEGF-A/VEGFR-2/AKT pathway, thereby exerting antitumor effect on LUAD.

Oestrogen Represses Noggin Expression by Interfering With BMP/Smad Signalling in ER Positive Breast Cancer.

BACKGROUND/AIM: As an antagonist of bone morphogenetic protein (BMP), Noggin facilitates osteolytic bone metastases from breast cancer. The present study aimed to further dissect its role in oestrogen receptor (ER) positive breast cancer. MATERIALS AND METHODS: Noggin expression in ER positive breast cancer cell lines (MCF-7 and T-47D) was determined under conditions of oestrogen deprivation and treatment with 17-ß-oestradiol (E2). Activation of Smad1/5/8 in the oestrogen-regulated Noggin was examined using recombinant human BMP7 (rhBMP7) and a BMP receptor inhibitor (LDN-193189). The influence of Noggin on cellular functions was evaluated in MCF-7 and T-47D cell lines. Responses to tamoxifen and chemotherapy drugs were determined in MCF-7 and T-47D cells with Noggin over-expression using MTT assay. RESULTS: Noggin expression was negatively correlated with ERα in breast cancers. Noggin was up-regulated upon oestrogen deprivation, an effect that was eliminated by E2 Furthermore, increased levels of phosphorylated Smad1/5/8 were observed in the oestrogen-deprived MCF-7 and T-47D cells, which was prevented by E2 and LDN-193189, respectively. BMP7-induced Noggin expression and activation of Smad1/5/8 was also prevented by E2 and LDN-193189. Noggin over-expression resulted in an increase in the proliferation of both MCF-7 and T-47D cells. MCF-7 and T-47D cells over-expressing Noggin exhibited a good tolerance to tamoxifen (TAM), DTX, and 5-FU, but the percentage of viable cells was higher compared with the controls. CONCLUSION: Noggin expression can be repressed by oestrogen through inference with the BMP/Smad signalling. Over-expression of Noggin promotes the proliferation of MCF-7 and T-47D cells, contributing to drug resistance.

Automatic semantic segmentation of EHG recordings by deep learning: An approach to a screening tool for use in clinical practice.

BACKGROUND AND OBJECTIVE: Preterm delivery is an important factor in the disease burden of the newborn and infants worldwide. Electrohysterography (EHG) has become a promising technique for predicting this condition, thanks to its high degree of sensitivity. Despite the technological progress made in predicting preterm labor, its use in clinical practice is still limited, one of the main barriers being the lack of tools for automatic signal processing without expert supervision, i.e. automatic screening of motion and respiratory artifacts in EHG records. Our main objective was thus to design and validate an automatic system of segmenting and screening the physiological segments of uterine origin in EHG records for robust characterization of uterine myoelectric activity, predicting preterm labor and help to promote the transferability of the EHG technique to clinical practice. METHODS: For this, we combined 300 EHG recordings from the TPEHG DS database and 69 EHG recordings from our own database (Ci2B-La Fe) of women with singleton gestations. This dataset was used to train and evaluate U-Net, U-Net++, and U-Net 3+ for semantic segmentation of the physiological and artifacted segments of EHG signals. The model's predictions were then fine-tuned by post-processing. RESULTS: U-Net 3+ outperformed the other models, achieving an area under the ROC curve of 91.4 % and an average precision of 96.4 % in detecting physiological activity. Thresholds from 0.6 to 0.8 achieved precision from 93.7 % to 97.4 % and specificity from 81.7 % to 94.5 %, detecting high-quality physiological segments while maintaining a trade-off between recall and specificity. Post-processing improved the model's adaptability by fine-tuning both the physiological and corrupted segments, ensuring accurate artifact detection while maintaining physiological segment integrity in EHG signals. CONCLUSIONS: As automatic segmentation proved to be as effective as double-blind manual segmentation in predicting preterm labor, this automatic segmentation tool fills a crucial gap in the existing preterm delivery prediction system workflow by eliminating the need for double-blind segmentation by experts and facilitates the practical clinical use of EHG. This work potentially contributes to the early detection of authentic preterm labor women and will allow clinicians to design individual patient strategies for maternal health surveillance systems and predict adverse pregnancy outcomes.

Boosting urea-assisted water splitting over P-MoO2@CoNiP through Mo leaching/reabsorption coupling CoNiP reconstruction.

Combining the urea oxidation reaction (UOR) with the hydrogen evolution reaction (HER) is an effective technology for energy-saving hydrogen production. Herein, a bifunctional electrocatalyst with CoNiP nanosheet coating on P-doped MoO2 nanorods (P-MoO2@CoNiP) is obtained via a two-step hydrothermal followed a phosphorization process. The catalyst demonstrates exceptional alkaline HER performance due to the formation of MoO2 and the dissolution/absorption of Mo. Meanwhile, the inclusion of Co and P in the P-MoO2@CoNiP catalyst facilitated the formation of NiOOH, enhancing UOR performance. Density functional theory calculations reveal that the hydrogen adsorption Gibbs free energy (ΔGH*) of P-MoO2@CoNiP is closer to 0 eV than CoNiP, favoring the HER. The catalyst only needs -0.08 and 1.38 V to reach 100 mA cm-2 for catalyzing the HER and UOR, respectively. The full urea electrolysis system driven by P-MoO2@CoNiP requires 1.51 V to achieve 100 mA cm-2, 120 mV lower than the traditional water electrolysis.

Direct and stable hydrogenation of CO2 to aromatics over a tandem catalyst Zn0.1Ti0.9Ox/HZSM-5.

Direct and stable conversion of CO2 to aromatics (CTA) is an attractive route for reducing CO2 emissions. However, due to the chemical inertness of CO2, direct CTA reaction with high aromatics selectivity is still challenging. In this work, a tandem catalyst Zn0.1Ti0.9Ox/HZSM-5 with appropriate density and strength of acid sites exhibits a high aromatics selectivity of 67.2% and long-term stability over 100 h. Furthermore, the total selectivity of benzene, toluene, and xylene achieves 24.1% over Zn0.1Ti0.9Ox/HZSM-5 with a modified hydrophilic surface. In addition, the CTA via the formate route has been determined in this reaction system.

Testing the ectomycorrhizal-dominance hypothesis for ecosystem multifunctionality in a subtropical mountain forest.

Mycorrhizal associations are key mutualisms that shape the structure of forest communities and multiple ecosystem functions. However, we lack a framework for predicting the varying dominance of distinct mycorrhizal associations in an integrated proxy of multifunctionality across ecosystems. Here, we used the datasets containing diversity of mycorrhizal associations and 18 ecosystem processes related to supporting, provisioning, and regulating services to examine how the dominance of ectomycorrhiza (EcM) associations affects ecosystem multifunctionality in subtropical mountain forests in Southwest China. Meanwhile, we synthesized the prevalence of EcM-dominant effects on ecosystem functioning in forest biomes. Our results demonstrated that elevation significantly modified the distributions of EcM trees and fungal dominance, which in turn influenced multiple functions simultaneously. Multifunctionality increased with increasing proportion of EcM associations, supporting the ectomycorrhizal-dominance hypothesis. Meanwhile, we observed that the impacts of EcM dominance on individual ecosystem functions exhibited different relationships among forest biomes. Our findings highlight the importance of ectomycorrhizal dominance in regulating multifunctionality in subtropical forests. However, this ectomycorrhizal feedback in shaping ecosystem functions cannot necessarily be generalized across forests. Therefore, we argue that the predictions for ecosystem multifunctionality in response to the shifts of mycorrhizal composition could vary across space and time.

Biomedical application of materials for external auditory canal: History, challenges, and clinical prospects.

Biomaterials play an integral role in treatment of external auditory canal (EAC) diseases. Regarding the special anatomic structure and physiological characteristics of EAC, careful selection of applicable biomaterials was essential step towards effective management of EAC conditions. The bioactive materials can provide reasonable biocompatibility, reduce risk of host pro-inflammatory response and immune rejection, and promote the healing process. In therapeutic procedure, biomaterials were employed for covering or packing the wound, protection of the damaged tissue, and maintaining of normal structures and functions of the EAC. Therefore, understanding and application of biomaterials was key to obtaining great rehabilitation in therapy of EAC diseases. In clinical practice, biomaterials were recognized as an important part in the treatment of different EAC diseases. The choice of biomaterials was distinct according to the requirements of various diseases. As a result, awareness of property regarding different biomaterials was fundamental for appropriate selection of therapeutic substances in different EAC diseases. In this review, we firstly introduced the characteristics of EAC structures and physiology, and EAC pathologies were summarized secondarily. From the viewpoint of biomaterials, the different materials applied to individual diseases were outlined in categories. Besides, the underlying future of therapeutic EAC biomaterials was discussed.

Aflatoxin B1-induced liver pyroptosis is mediated by disturbing the gut microbial metabolites: The roles of pipecolic acid and norepinephrine.

The disturbed gut microbiota is a key factor in activating the aflatoxin B1 (AFB1)-induced liver pyroptosis by promoting inflammatory hepatic injury; however, the pathogen associated molecular pattern (PAMP) from disturbed gut microbiota and its mechanism in activating liver pyroptosis remain undefined. By transplanting AFB1-originated fecal microbiota and sterile fecal microbial metabolites filtrate, we determined the association of PAMP in AFB1-induced liver pyroptosis. Notably, AFB1-originated sterile fecal microbial metabolites filtrate were more active in triggering liver pyroptosis in mice, as compared to parental fecal microbiota. This result supported a critical role of the metabolic homeostasis of gut microbiota in AFB1-induced liver pyroptosis, rather than an injurious response to direct exposure of AFB1 in liver. Among the gut-microbial metabolites, pipecolic acid and norepinephrine were proposed to bind TLR4 and NLRP3, the upstream proteins of pyroptosis signaling pathway. Besides, the activations of TLR4 and NLRP3 were linearly correlated with the concentrations of pipecolic acid and norepinephrine in the serum of mice. In silenced expression of TLR4 and NLRP3 in HepG2 cells, pipecolic acid or norepinephrine did not able to activate hepatocyte pyroptosis. These results demonstrated the necessity of gut microbial metabolism in sustaining liver homeostasis, as well as the potential to provide new insights into targeted intervention for AFB1 hepatotoxicity.

LncRNA DYNLRB2-AS1 promotes gemcitabine resistance of nasopharyngeal carcinoma by inhibiting the ubiquitination degradation of DHX9 protein.

Gemcitabine (GEM) based induction chemotherapy is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, approximately 15 % of patients are still resistant to GEM-containing chemotherapy, which leads to treatment failure. Nevertheless, the underlying mechanisms of GEM resistance remain poorly understood. Herein, based on a microarray analysis, we identified 221 dysregulated lncRNAs, of which, DYNLRB2-AS1 was one of the most upregulated lncRNAs in GEM-resistance NPC cell lines. DYNLRB2-AS1 was shown to function as contain an oncogenic lncRNA that promoted NPC GEM resistance, cell proliferation, but inhibited cell apoptosis. Mechanistically, DYNLRB2-AS1 could directly bind to the DHX9 protein and prevent its interaction with the E3 ubiquitin ligase PRPF19, and thus blocking PRPF19-mediated DHX9 degradation, which ultimately facilitated the repair of DNA damage in the presence of GEM. Clinically, higher DYNLRB2-AS1 expression indicated an unfavourable overall survival of NPC patients who received induction chemotherapy. Overall, this study identified the oncogenic lncRNA DYNLRB2-AS1 as an independent prognostic biomarker for patients with locally advanced NPC and as a potential therapeutic target for overcoming GEM chemoresistance in NPC.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

ScRNA-seq revealed the tumor microenvironment heterogeneity related to the occurrence and metastasis in upper urinary tract urothelial carcinoma.

Metastasis is the greatest clinical challenge for UTUCs, which may have distinct molecular and cellular characteristics from earlier cancers. Herein, we provide single-cell transcriptome profiles of UTUC para cancer normal tissue, primary tumor lesions, and lymphatic metastases to explore possible mechanisms associated with UTUC occurrence and metastasis. From 28,315 cells obtained from normal and tumor tissues of 3 high-grade UTUC patients, we revealed the origin of UTUC tumor cells and the homology between metastatic and primary tumor cells. Unlike the immunomicroenvironment suppression of other tumors, we found no immunosuppression in the tumor microenvironment of UTUC. Moreover, it is imperative to note that stromal cells are pivotal in the advancement of UTUC. This comprehensive single-cell exploration enhances our comprehension of the molecular and cellular dynamics of metastatic UTUCs and discloses promising diagnostic and therapeutic targets in cancer-microenvironment interactions.

PJA1-mediated suppression of pyroptosis as a driver of docetaxel resistance in nasopharyngeal carcinoma.

Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells. Mechanistically, PJA1 promotes the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, which further facilitates DRP1 phosphorylation at S637 and reduced mitochondrial reactive oxygen species production, resulting in suppression of GSDME-mediated pyroptosis and the antitumour immune response. PGAM5 knockdown fully restores the docetaxel sensitization effect of PJA1 knockdown. Moreover, pharmacological targeting of PJA1 with the small molecule inhibitor RTA402 enhances the docetaxel sensitivity of nasopharyngeal carcinoma in vitro and in vivo. Clinically, high PJA1 expression indicates inferior survival and poor clinical efficacy of TPF IC in nasopharyngeal carcinoma patients. Our study emphasizes the essential role of E3 ligases in regulating chemoresistance and provides therapeutic strategies for nasopharyngeal carcinoma based on targeting the ubiquitin-proteasome system.

The effects of vitamin D and gene polymorphisms on susceptibility to thyroid peroxidase antibody positivity.

BACKGROUND: The etiology of Hashimoto's thyroiditis (HT) involves genetic and environmental factors. There is a lack of clarity regarding the relationship between Vitamin D and HT. This study aimed to investigate the effect of Vitamin D and gene polymorphisms on thyroid peroxidase antibody (TPOAb) positivity. METHODS: A total of 9,966 participants were included from a survey conducted in East China from 2014 to 2016. We measured the levels of 25(OH)D, thyroid hormones and autoimmune antibodies. rs11675434, rs9277555, and rs301799 were genotyped. Based on these 3 SNPs, a weighted genetic risk score was calculated for TPOAb. RESULTS: The proportion of females in the TPOAb-positive group was greater than that in the TPOAb-negative group (74.2% vs. 57.2%, P<0.001). Vitamin D levels were lower in the TPOAb-positive group than in the TPOAb-negative group (40.07±11.87 vs. 40.80±12.84, P=0.01). The GG genotype of rs9277555 and the TT genotype of rs11675434 were correlated with the risk of TPOAb positivity (OR=1.34, 95% CI 1.13-1.59, P=0.001; OR=1.29, 95% CI 1.06-1.58, P=0.01). TPOAb-GRS was associated with TPOAb positivity (OR=3.17, 95% CI 1.72-5.84; P<0.001). When stratified by Vitamin D group, the association between TPOAb-GRS and TPOAb positivity existed only in the Vitamin D deficiency group (OR=3.41, 95% CI 1.73-6.70 P<0.001) but not in the control group (OR=2.45, 95% CI 0.59-10.19, P=0.22). CONCLUSIONS: This study suggested that TPOAb-GRS was associated with TPOAb positivity in the Han Chinese population, mainly due to rs9277555 and rs11675434. The hereditary effect of TPOAb positivity differed depending on Vitamin D status.

Progress and trends in photodynamic therapy research in oral science: A bibliometric analysis.

BACKGROUND: Photodynamic therapy is garnering increasing attention in oral science. Despite its promising potential, further exploration is warranted to delve into the research paradigms and evolving trends within oral science. Therefore, this study aimed to conduct a comprehensive bibliometric analysis of photodynamic therapy in oral science (PDTOS), investigating research landscapes, identifying key contributors, analyzing collaborative networks, pinpointing emerging research directions, and exploring factors influencing high citations. METHODS: Research and review articles in PDTOS were retrieved from the Web of Science Core Collection database up to December 31, 2023. The R package "bibliometrix" and VOSviewer were utilized for visualizing collaboration networks and keyword co-occurrence, alongside trend analysis. Negative binomial regression was used to model factors affecting citation counts. RESULTS: A total of 2784 articles with significant international collaboration (23.14 %) were analyzed. Brazil, China, the USA, Iran, and Italy led in publications, with predominant USA-European collaborations. The University of Sao Paulo in Brazil was the most published institution in the field. Photodiagnosis and Photodynamic Therapy was the core journal in the field and has the highest number of publications. The main research fields included photodynamic therapy, antibacterial and anticancer treatment, management, and peri­implant periodontitis, with a recent focus on peri­implantitis. Factors such as international cooperation, funding, article age, type, author count, and references significantly influenced citations. CONCLUSIONS: This research provided valuable insights into PDTOS trends and knowledge structures. These findings underscored a significant increase in the number of PDTOS publications, urging strengthened international cooperation. Emerging research has focused on peri­implantitis and nano-photosensitizer materials. Authors should consider various citation-related factors in their research endeavors.

Prevotella copri alleviates hyperglycemia and regulates gut microbiota and metabolic profiles in mice.

Prevotella copri is the dominant species of the Prevotella genus in the gut, which is genomically heterogeneous and difficult to isolate; hence, scarce research was carried out for this species. This study aimed to investigate the effect of P. copri on hyperglycemia. Thirty-nine strains were isolated from healthy individuals, and three strains (HF2123, HF1478, and HF2130) that had the highest glucose consumption were selected to evaluate the effects of P. copri supplementation on hyperglycemia. Microbiomics and non-target metabolomics were used to uncover the underlying mechanisms. Oral administration of P. copri in diabetic db/db mice increased the expression and secretion of glucagon-like peptide-1 (GLP-1), significantly improved hyperglycemia, insulin resistance, and lipid accumulation, and alleviated the pathological morphology in the pancreas, liver, and colon. P. copri changed the composition of the gut microbiota of diabetic db/db mice, which was characterized by increasing the ratio of Bacteroidetes to Firmicutes and increasing the relative abundance of genera Bacteroides, Akkermansia, and Faecalibacterium. After intervention with P. copri, fecal metabolic profiling showed that fumaric acid and homocysteine contents decreased, and glutamine contents increased. Furthermore, amino acid metabolism and cAMP/PKA signaling pathways were enriched. Our findings indicate that P. copri improved glucose metabolism abnormalities in diabetic db/db mice. Especially, one of the P. copri strains, HF2130, has shown superior performance in improving hyperglycemia, which may have the potential as a probiotic against hyperglycemia. IMPORTANCE: As a core member of the human intestinal ecosystem, Prevotelal copri has been associated with glucose metabolic homeostasis in previous studies. However, these results have often been derived from metagenomic studies, and the experimental studies have been based solely on the type of strain DSM 18205T. Therefore, more experimental evidence from additional isolates is needed to validate the results according to their high genomic heterogeneity. In this study, we isolated different branches of strains and demonstrated that P. copri could improve the metabolic profile of hyperglycemic mice by modulating microbial activity. This finding supports the causal contribution of P. copri in host glucose metabolism.

Machine Learning Identification of Nutrient Intake Variations across Age Groups in Metabolic Syndrome and Healthy Populations.

This study undertakes a comprehensive examination of the intricate link between diet nutrition, age, and metabolic syndrome (MetS), utilizing advanced artificial intelligence methodologies. Data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018 were meticulously analyzed using machine learning (ML) techniques, specifically extreme gradient boosting (XGBoost) and the proportional hazards model (COX). Using these analytic methods, we elucidated a significant correlation between age and MetS incidence and revealed the impact of age-specific dietary patterns on MetS. The study delineated how the consumption of certain dietary components, namely retinol, beta-cryptoxanthin, vitamin C, theobromine, caffeine, lycopene, and alcohol, variably affects MetS across different age demographics. Furthermore, it was revealed that identical nutritional intakes pose diverse pathogenic risks for MetS across varying age brackets, with substances such as cholesterol, caffeine, and theobromine exhibiting differential risks contingent on age. Importantly, this investigation succeeded in developing a predictive model of high accuracy, distinguishing individuals with MetS from healthy controls, thereby highlighting the potential for precision in dietary interventions and MetS management strategies tailored to specific age groups. These findings underscore the importance of age-specific nutritional guidance and lay the foundation for future research in this area.