Impact of DNA ligase inhibition on the nick sealing of polß nucleotide insertion products at the downstream steps of base excision repair pathway.

DNA ligase (LIG) I and IIIα finalize base excision repair (BER) by sealing a nick product after nucleotide insertion by DNA polymerase (pol) ß at the downstream steps. We previously demonstrated that a functional interplay between polß and BER ligases is critical for efficient repair, and polß mismatch or oxidized nucleotide insertions confound final ligation step. Yet, how targeting downstream enzymes with small molecule inhibitors could affect this coordination remains unknown. Here, we report that DNA ligase inhibitors, L67 and L82-G17, slightly enhance hypersensitivity to oxidative stress-inducing agent, KBrO3, in polß+/+ cells more than polß-/- null cells. We showed less efficient ligation after polß nucleotide insertions in the presence of the DNA ligase inhibitors. Furthermore, the mutations at the ligase inhibitor binding sites (G448, R451, A455) of LIG1 significantly affect nick DNA binding affinity and nick sealing efficiency. Finally, our results demonstrated that the BER ligases seal a gap repair intermediate by the effect of polß inhibitor that diminishes gap filling activity. Overall, our results contribute to understand how the BER inhibitors against downstream enzymes, polß, LIG1, and LIGIIIα, could impact the efficiency of gap filling and subsequent nick sealing at the final steps leading to the formation of deleterious repair intermediates.

Ultra-low frequency magnetic energy focusing for highly effective wireless powering of deep-tissue implantable electronic devices.

The limited lifespan of batteries is a challenge in the application of implantable electronic devices. Existing wireless power technologies such as ultrasound, near-infrared light and magnetic fields cannot charge devices implanted in deep tissues, resulting in energy attenuation through tissues and thermal generation. Herein, an ultra-low frequency magnetic energy focusing (ULFMEF) methodology was developed for the highly effective wireless powering of deep-tissue implantable devices. A portable transmitter was used to output the low-frequency magnetic field (<50 Hz), which remotely drives the synchronous rotation of a magnetic core integrated within the pellet-like implantable device, generating an internal rotating magnetic field to induce wireless electricity on the coupled coils of the device. The ULFMEF can achieve energy transfer across thick tissues (up to 20 cm) with excellent transferred power (4-15 mW) and non-heat effects in tissues, which is remarkably superior to existing wireless powering technologies. The ULFMEF is demonstrated to wirelessly power implantable micro-LED devices for optogenetic neuromodulation, and wirelessly charged an implantable battery for programmable electrical stimulation on the sciatic nerve. It also bypassed thick and tough protective shells to power the implanted devices. The ULFMEF thus offers a highly advanced methodology for the generation of wireless powered biodevices.

Long-term efficacy analysis of radiotherapy and local management of metastases in patients with newly diagnosed oligometastatic nasopharyngeal carcinoma: A prospective, single-arm, single-center clinical study.

PURPOSE: We conducted a single-center, single-arm study (NCT03129412) to prospectively analyze the long-term outcomes of newly diagnosed patients with oligometastatic nasopharyngeal carcinoma (NPC) who received radical radiotherapy and local treatment of metastases. PATIENTS AND METHODS: Patients who reached disease controll after platinum-based palliative chemotherapy continued to receive radical radiotherapy for the nasopharyngeal region and neck. Appropriate local treatments were selected to treat the metastatic lesions. The primary endpoint of this study was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). RESULTS: Fifty-one patients were included in the final analysis. During a median follow-up of 60 months, the median OS and PFS were 53.87 and 24.23 months, respectively. The 1-year, 3-year, and 5-year PFS and OS rates were 76.5 %, 38.1 %, and 31.8 % and 98 %, 75.4 %, 45.6 %, respectively. Both single and multivariate analysis indicated that maintenance therapy after radiotherapy could significantly increase PFS (36.43 vs. 16.1 months, P = 0.005). The OS of patients with single organ metastasis was significantly better than that of patients with double organ metastasis (P = 0.001). In addition, the number of metastatic organs also significantly affected PFS in the multifactor analysis. CONCLUSION: Patients with newly diagnosed oligometastatic NPC can achieve long-term survival after receiving radical radiotherapy to the primary site and local treatment for metastases.

High toxin concentration in pollen may deter collection by bees in butterfly-pollinated Rhododendron molle.

BACKGROUNDS AND AIMS: The hypothesis that plants evolve features that protect accessible pollen from consumption by flower visitors remains poorly understood. METHODS: To explore potential chemical defenses against pollen consumption, we examined the pollinator assemblage, foraging behaviour, visitation frequency and pollen transfer efficiency in Rhododendron molle, a highly toxic shrub containing Rhodojaponin III. Nutrient (protein and lipid) and toxic components in pollen and other tissues were measured. KEY RESULTS: Overall in the five populations, floral visits by butterflies and bumblebees were relatively more frequent than visits by honeybees. All foraged for nectar but not pollen. Butterflies did not differ from bumblebees in the amount of pollen removed per visit, but deposited more pollen per visit. Pollination experiments indicated that R. molle was self-compatible, but both fruit and seed production were pollen limited. Our analysis indicated that the pollen was not protein-poor and had a higher concentration of the toxic compound Rhodojaponin III than petals and leaves, which compound was undetectable in nectar. CONCLUSION: Pollen toxicity in Rhododendron flowers may discourage pollen robbers (bees) from taking the freely accessible pollen grains, while the toxin-free nectar rewards effective pollinators, promoting pollen transfer. This preliminary study supports the hypothesis that chemical defense in pollen would be likely to evolve in species without physical protection from pollinivores.

Technological Advances of Wearable Device for Continuous Monitoring of In Vivo Glucose.

Managing diabetes is a chronic challenge today, requiring monitoring and timely insulin injections to maintain stable blood glucose levels. Traditional clinical testing relies on fingertip or venous blood collection, which has facilitated the emergence of continuous glucose monitoring (CGM) technology to address data limitations. Continuous glucose monitoring technology is recognized for tracking long-term blood glucose fluctuations, and its development, particularly in wearable devices, has given rise to compact and portable continuous glucose monitoring devices, which facilitates the measurement of blood glucose and adjustment of medication. This review introduces the development of wearable CGM-based technologies, including noninvasive methods using body fluids and invasive methods using implantable electrodes. The advantages and disadvantages of these approaches are discussed as well as the use of microneedle arrays in minimally invasive CGM. Microneedle arrays allow for painless transdermal puncture and are expected to facilitate the development of wearable CGM devices. Finally, we discuss the challenges and opportunities and look forward to the biomedical applications and future directions of wearable CGM-based technologies in biological research.

Coupling of nanostraws with diverse physicochemical perforation strategies for intracellular DNA delivery.

Effective intracellular DNA transfection is imperative for cell-based therapy and gene therapy. Conventional gene transfection methods, including biochemical carriers, physical electroporation and microinjection, face challenges such as cell type dependency, low efficiency, safety concerns, and technical complexity. Nanoneedle arrays have emerged as a promising avenue for improving cellular nucleic acid delivery through direct penetration of the cell membrane, bypassing endocytosis and endosome escape processes. Nanostraws (NS), characterized by their hollow tubular structure, offer the advantage of flexible solution delivery compared to solid nanoneedles. However, NS struggle to stably self-penetrate the cell membrane, resulting in limited delivery efficiency. Coupling with extra physiochemical perforation strategies is a viable approach to improve their performance. This study systematically compared the efficiency of NS coupled with polyethylenimine (PEI) chemical modification, mechanical force, photothermal effect, and electric field on cell membrane perforation and DNA transfection. The results indicate that coupling NS with PEI modification, mechanical force, photothermal effects provide limited enhancement effects. In contrast, NS-electric field coupling significantly improves intracellular DNA transfection efficiency. This work demonstrates that NS serve as a versatile platform capable of integrating various physicochemical strategies, while electric field coupling stands out as a form worthy of primary consideration for efficient DNA transfection.

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study.

OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. METHOD: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006). CONCLUSION: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Respective evolution of soil and biochar on competitive adsorption mechanisms for Cd(II), Ni(II), and Cu(II) after 2-year natural ageing.

To reveal the respective evolution of soil and biochar on competitive heavy metal adsorption mechanisms after natural ageing, three soils and two biochars were tested in this study. The soil-biochar interlayer samples were buried in the field for 0.5, 1, and 2 years, for which competitive adsorption characteristics and mechanisms of soils and biochars in four systems (Cd, Cd+Ni, Cd+Cu, and Cd+Ni+Cu) were investigated. Results showed that physicochemical properties, adsorption capacity and mechanisms of soils and biochars all changed the most in the first 0.5 years. The properties and adsorption capacity of biochars gradually weakened with the ageing time, meanwhile, those of soils gradually enhanced. After co-ageing with acidic soil for 0.5 years, the Cd(II) adsorption capacity of modified biochar decreased by 86.59% in the ternary system; meanwhile, that of acidic soil increased by 65.52%. The contributions of mineral mechanisms decreased significantly, while non-mineral mechanisms were slightly affected by ageing. This study highlighted that when using biochar to remediate heavy metal-contaminated soils, biochar should be applied at least half a year in advance before planting crops so that biochar can fully contact and react with the soil.

Integrated electronic/fluidic microneedle system for glucose sensing and insulin delivery.

Background: Precise and dynamic blood glucose regulation is paramount for both diagnosing and managing diabetes. Continuous glucose monitoring (CGM) coupled with insulin pumps forms an artificial pancreas, enabling closed-loop control of blood glucose levels. Indeed, this integration necessitates advanced micro-nano fabrication techniques to miniaturize and combine sensing and delivery modules on a single electrode. While microneedle technology can mitigate discomfort, concerns remain regarding infection risk and potential sensitivity limitations due to their short needle length. Methods: This study presents the development of an integrated electronic/fluidic microneedle patch (IEFMN) designed for both glucose sensing and insulin delivery. The use of minimally invasive microneedles mitigates nerve contact and reduces infection risks. The incorporation of wired enzymes addresses the issue of "oxygen deprivation" during glucose detection by decreasing the reliance on oxygen. The glucose-sensing electrodes employ wired enzyme functionalization to achieve lower operating voltages and enhanced resilience to sensor interference. The hollow microneedles' inner channel facilitates precise drug delivery for blood glucose regulation. Results: Our IEFMN-based system demonstrated high sensitivity, selectivity, and a wide response range in glucose detection at relatively low voltages. This effectively reduced interference from both external and internal active substances. The microneedle array ensured painless and minimally invasive skin penetration, while wired enzyme functionalization not only lowered sensing potential but also improved glucose detection accuracy. In vivo, experiments conducted in rats showed that the device could track subcutaneous glucose fluctuations in real-time and deliver insulin to regulate blood glucose levels. Conclusions: Our work suggests that the IEFMN-based system, developed for glucose sensing and insulin delivery, exhibits good performance during in vivo glucose detection and drug delivery. It holds the potential to contribute to real-time, intelligent, and controllable diabetes management.

Effects of soil water content on Cd immobilization and uptake by leek with the combined application of biochar and organic fertilizer.

This study investigated the effects of soil water content on Cd immobilization and uptake by leek with the combined application of biochar and organic fertilizer using mechanism experiment and pot experiment. Mechanism experiment was conducted with the three-layer mesh method, which can reveal the individual mechanisms and contributions of biochar and soil to Cd immobilization. The results of mechanism experiment showed that the Cd adsorption amount by biochar was very little at low soil water content (θw = 20%, w/w), and both of Cd adsorption amount and rate significantly increased at higher θw (40% and 60%). The Cd immobilization by biochar at higher θw (40% and 60%) was significantly better than that at low θw (20%) in soils because F1 (percentages of exchangeable Cd) decreased with increasing moisture. For example, the F1 percentages were 58.27%, 40.67%, and 38.46% in the soil at 4.40 mg·kg-1 under M20, M40, and M60 (θw = 20%, 40%, 60%) at day 120, respectively. The results of pot experiment showed that the Cd in leek leaves and roots continuously accumulated with planting time in each batch, and biochar and organic fertilizer treatments significantly reduced the Cd enrichment in leek. Combined treatment of biochar and organic fertilizer (BO) is superior to biochar treatments (BC) and CK for Cd immobilization in soil. For example, the percentages of F1 under the treatments of CK, BC, and BO were 64.43%, 49.13%, and 43.67% at 75% field water capacity treatment, respectively. For the same treatment, with increasing water contents, the better the Cd was immobilized in the soil and the greater the leek biomass. However, the total uptake of Cd by leek were increased by promoting crop growth under water content conditions.

What influences newly graduated registered nurses' intention to leave the nursing profession? An integrative review.

BACKGROUND: Newly graduated registered nurses leaving the nursing profession in the early stages of their career have enormous financial and time implications for nursing organizations and affect the quality of nursing care. OBJECTIVE: To identify the factors influencing newly graduated registered nurses' intention to leave the nursing profession over the past 10 years. METHODS: The framework developed by Whittemore and Knafl was used to conduct this integrative review. An electronic search was conducted for English articles to identify research studies published between 2011-2022 using the following databases of PubMed, MEDLINE, CINAHL, PsycINFO, and Scopus. Eligible publications were critically reviewed and scored using the Critical Appraisal Skills Program Checklist and the Center for Evidence-Based Management appraisal. RESULTS: Twenty-one studies were analyzed. The main factors affecting newly graduated registered nurses' intention to leave the nursing profession included demographic factors (age, educational level, year of experience, professional title, employment status, health status, shift, hospital location and size), supervisor and peer support, challenges in the workplace, cognitive and affective response to work, work environment (collegial nurse-physician relations, insufficient staffing level, person-work environment fit), gender stereotypes, autonomous motivation, role models, and resilience. CONCLUSIONS: The factors affecting newly graduated registered nurses' intention to leave the nursing profession are multifaceted and should receive continuous attention from nurse managers. The findings provide more comprehensive for nurse administrators to develop intervention strategies to mitigate newly graduated registered nurses' turnover intention.

Optimal dosage of rituximab for children with Burkitt lymphoma.

The current chemotherapy treatments have led to an improvement in survival rates for pediatric Burkitt's lymphoma (BL). Survival in children with high-grade, mature B-cell non-Hodgkin's lymphoma (B-NHL) has been prolonged by six rituximab doses combined with chemotherapy, whereas the efficacy of four doses has not been reported. This study aimed to explore optimal therapeutic strategies-the number of doses of rituximab based on different risk groups-and also aim to investigate the clinical characteristics of Chinese pediatric BL. This study consecutively enrolled children with BL in Beijing Children's Hospital who received French-American-British mature B-cell lymphoma 96 (FAB/LMB96). The patients were divided into three groups: R0 group (chemotherapy alone), R6 group (chemotherapy combined with six rituximab doses), and R4 group (chemotherapy combined with four rituximab doses). The clinical characteristics and outcomes were evaluated. Univariate and multivariate analyses and prognostic nomogram were used to assess prognostic factors. A nomogram was developed that predicted overall survival based on the Cox proportional hazards model, and the concordance index (C-index) and a calibration curve were used to determine its predictive and discriminatory capacity. We enrolled 385 boys and 71 girls, with a median age of 6 years (1-14 years). Of these, 296 patients (65%) had initial abdominal symptoms, 182 (40%) had bulky disease, 46 (10%) had B symptoms, 77 (16.9%) had BL-ALL (blasts ≥ 25% in bone marrow (BM)), 96 (21%) had central nervous system (CNS) disease, 406 (89%) were in stages III-IV, 378 (83%) were in group C, 170 (37.2%) had lactate dehydrogenase (LDH) levels ≥ 1000 U/L at initial diagnosis, and 137 (30%) had tumor lysis syndrome. The R0, R6, and R4 groups included 79, 144, and 227 patients, respectively. Six patients were excluded due to treatment withdrawal for various reasons. The 3-year overall survival (OS) and event-free survival (EFS) percentages were 92% ± 1.3% and 91.3% ± 1.3%, respectively, in all cohorts, whereas the 3-year EFS percentage was 83.5% ± 4.2%, 93% ± 2.1%, and 92.9% ± 1.8% in the R0, R6, and R4 groups, respectively (P = 0.025). The nomogram included four important variables based on a multivariate analysis of the primary cohort: course of disease ≤ 20 days, presence of bulky disease at the beginning of diagnosis, central nervous system(CNS) invasion, and dosage of rituximab. The calibration curve showed that the nomogram was able to predict 3-year OS accurately. The C-index of the nomogram for OS prediction was 0.79 for both cohorts. In our hospital, pediatric BL was more commonly observed in school-age boys with an abdominal mass and mostly in advanced stages at initial diagnosis. The FAB/LMB96 regimen combined with rituximab significantly increased survival outcomes. We observed no significant differences between four and six doses of rituximab in terms of treatment outcomes. The proposed nomogram provides an individualized risk estimate of OS in patients with BL and may assist treatment decision-making or rituximab dose design.

Use of 18F-FDG PET/MRI as an Initial Staging Procedure for Nasopharyngeal Carcinoma.

BACKGROUND: Compared with the conventional work-up (CWU) including computed tomography (CT) of the chest and abdomen, MRI of the head and neck, and skeletal scintigraphy, positron emission tomography (PET)/MRI might improve diagnostic accuracy, shorten the work-up time, and reduce false-positive (FP) findings in patients with nasopharyngeal carcinoma (NPC). However, evidence of cost-effectiveness is needed for the adoption of PET/MRI for the initial staging in NPC. PURPOSE: To evaluate the cost-effectiveness and clinical value of PET/MRI as an initial staging procedure for NPC. STUDY TYPE: Retrospective cohort cost effectiveness study. SUBJECTS: Three hundred forty-three patients with a median age of 51 (13-81) years underwent PET/MRI before treatment (the PET/MRI group) and the remaining 677 patients with a median age of 55 (15-95) years only underwent CWU (the CWU group). There were 80 (23.3%) females and 193 (28.5%) females in the PET/MRI and CWU groups, respectively. FIELD STRENGTH/SEQUENCE: 3-T integrated PET/MRI system, diffusion-weighted echo-planar imaging (b = 0 and 1000 s/mm2 ) and [18F] fluorodeoxyglucose PET. ASSESSMENT: The primary end point was the FP rate. Costs were determined as issued in 2021 by the Medical Insurance Administration Bureau of Zhejiang, China. STATISTICAL TESTS: Incremental cost effectiveness ratio (ICER) measured cost of using PET/MRI per percent of patients who avoided a FP. A P-value <0.05 was considered statistically significant. RESULTS: For the whole group, the de novo metastatic disease rate was 5.2% (53/1020). A total of 187 patients with FP results were observed. Significantly more patients with FP results were observed in the CWU group compared to the PET/MRI group (25.6% vs. 4.1%). The ICER was $54 for each percent of patients avoiding a FP finding. DATA CONCLUSION: Compared with CWU, PET/MRI may reduce the FP risk. Furthermore, PET/MRI may be cost-effective as an initial staging procedure for NPC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 6.

Bacteriology of Different Phenotypes of Chronic Rhinosinusitis.

OBJECTIVES: Chronic rhinosinusitis (CRS) reduces the health-related quality of life and subsequently causes a tremendous socio-economic impact. Although many studies have been conducted, few have identified a relationship between bacteriological characteristics and different phenotypes or endotypes. Therefore, this study aimed to elucidate the recent trends in bacterial cultures from different types of CRS in the Asian population. METHODS: This retrospective case-control study recruited patients diagnosed with CRS who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. The patients were classified into those with chronic rhinosinusitis with nasal polyps (CRSwNP)/chronic rhinosinusitis without nasal polyps (CRSsNP), eosinophilic chronic rhinosinusitis (eCRS)/non-eosinophilic chronic rhinosinusitis (NECRS), and central compartment atopic disease (CCAD)/lateral-dominant nasal polyp (LDNP) groups. The demographic data and bacteriological characteristics of the groups were analyzed. RESULTS: We included 503 patients, identifying no significant difference between CRSwNP and CRSsNP for several common bacteria in CRS. The number of Staphylococcus epidermidis isolates in culture was significantly higher in the NECRS group (50.46% vs. 32.56%, p = 0.0003) than that in the eCRS group. The number of methicillin-resistant Staphylococcus aureus (MRSA; 8.51% vs. 2.35%, p = 0.0221) positive isolates was significantly higher in the CCAD group than that in the LDNP group. CONCLUSIONS: This was the first study in Asia to analyze the relationship between bacteriological characteristics and CCAD. MRSA is significantly higher in the CCAD group than that in the LDNP group. Recognizing the unique microbiology of CRSwNP, eCRS, and CCAD is crucial when selecting antimicrobial therapy to lessen the socio-economic impact. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1071-1076, 2024.

Adaptive scatter kernel deconvolution modeling for cone-beam CT scatter correction via deep reinforcement learning.

BACKGROUND: Scattering photons can seriously contaminate cone-beam CT (CBCT) image quality with severe artifacts and substantial degradation of CT value accuracy, which is a major concern limiting the widespread application of CBCT in the medical field. The scatter kernel deconvolution (SKD) method commonly used in clinic requires a Monte Carlo (MC) simulation to determine numerous quality-related kernel parameters, and it cannot realize intelligent scatter kernel parameter optimization, causing limited accuracy of scatter estimation. PURPOSE: Aiming at improving the scatter estimation accuracy of the SKD algorithm, an intelligent scatter correction framework integrating the SKD with deep reinforcement learning (DRL) scheme is proposed. METHODS: Our method firstly builds a scatter kernel model to iteratively convolve with raw projections, and then the deep Q-network of the DRL scheme is introduced to intelligently interact with the scatter kernel to achieve a projection adaptive parameter optimization. The potential of the proposed framework is demonstrated on CBCT head and pelvis simulation data and experimental CBCT measurement data. Furthermore, we have implemented the U-net based scatter estimation approach for comparison. RESULTS: The simulation study demonstrates that the mean absolute percentage error (MAPE) of the proposed method is less than 9.72% and the peak signal-to-noise ratio (PSNR) is higher than 23.90 dB, while for the conventional SKD algorithm, the minimum MAPE is 17.92% and the maximum PSNR is 19.32 dB. In the measurement study, we adopt a hardware-based beam stop array algorithm to obtain the scatter-free projections as a comparison baseline, and our method can achieve superior performance with MAPE < 17.79% and PSNR > 16.34 dB. CONCLUSIONS: In this paper, we propose an intelligent scatter correction framework that integrates the physical scatter kernel model with DRL algorithm, which has the potential to improve the accuracy of the clinical scatter correction method to obtain better CBCT imaging quality.

Competitive adsorption behaviors and mechanisms of Cd, Ni, and Cu by biochar when coexisting with microplastics under single, binary, and ternary systems.

In this study, the effects of coexistence with microplastics and co-ageing with the soil on adsorption behaviors and mechanisms of biochar for heavy metals were investigated. Adsorption experiments of Cd, Ni, and Cu by microplastics, biochar, and their combination were conducted in single, binary, and ternary systems. The results indicated that the heavy metal adsorption by microplastics was ranked as Ni > Cd > Cu, which increased with decreasing particle size, and the adsorption capacity of microplastics was enhanced after dry-wet and freeze-thaw ageing. Biochar preferentially adsorbed Cd in the single system, while the maximum adsorption of Cu was observed in the binary and ternary systems due to the minimizing impact of competition on the Cu adsorption by biochar. The heavy metal adsorption by the combination of microplastics and biochar was less than that by single biochar, and the smaller the particle size of microplastics, the greater the negative effects on heavy metal adsorption. Coexistence with microplastics reduced Cd adsorption of biochar by 0.72 %-50.35 %, Ni adsorption by 1.17 %-30.43 %, and Cu adsorption by 5.78 %-47.88 %, respectively. Moreover, coexistence with microplastics exacerbated the adverse impacts of competition on biochar adsorption for heavy metals. The contribution percentages of biochar mineral mechanisms for heavy metal adsorption were ranked as Cu > Cd > Ni. When coexisting with microplastics or after ageing, the mineral mechanisms of heavy metal adsorption by biochar significantly decreased. This study investigated the competitive adsorption behaviors and mechanisms of heavy metals by biochar when coexisting with microplastics, which highlighted that the application of biochar for the remediation of heavy metal pollution should be concerned with the impacts of microplastics.

MiR-4521 affects the propagation of Cryptosporidium parvum in HCT-8 cells through targeting foxm1 by regulating cell apoptosis.

Cryptosporidium parvum could regulate the expression of microRNAs of epithelial cells to facilitate its intracellular propagation. MiR-4521 has been reported to play an important role during the development and progression of tumors and infectious diseases by regulating cell proliferation, apoptosis, and autophagy. However, the implication of miR-4521 during C. parvum infection was still unknown. In this study, the expression of miR-4521 was found to be upregulated in HCT-8 cells infected with C. parvum from 8 h post-infection (pi) to 48 hpi, and its upregulation would be related with the TLR/NF-κB signal pathway during C. parvum infection. One potential target of miR-4521, foxm1, was down-regulated in HCT-8 cells from 24 hpi to 48 hpi, and the expression of foxm1 was negatively regulated by miR-4521. The target relationship between miR-4521 and foxm1 was further validated by using dual luciferase reporter assay. Further studies showed that miR-4521 promoted the propagation of C. parvum in HCT-8 cells through targeting foxm1 by regulating BCL2-mediating cell apoptosis. These results contribute to further understanding of the regulatory mechanisms of host miRNAs during Cryptosporidium infection.

ASC/inflammasome-independent pyroptosis in ovarian cancer cells through translational augmentation of caspase-1.

Canonical pyroptosis is type of programmed cell death depending on active caspase-1, and the inflammasome carries out caspase-1 activation. Here, we showed that docosahexaenoic acid (DHA) induced ovarian cancer cell deaths in caspase-1-dependent manner. DHA increased caspase-1 activity and led to interleukin-1ß secretion and gasdermin D cleavage while disulfiram inhibited DHA-induced cell death, suggesting that DHA triggered pyroptosis. Intriguingly, ASC, the molecule recruiting caspase-1 to inflammasome for activation, was dispensable for DHA-induced pyroptosis. Instead, we observed remarkable elevation in caspase-1 abundance concurrent with the activation of caspase-1 in DHA-treated cells. As ectopically overexpressing caspase-1 resulted in robust amount of active caspase-1, we reason that DHA activates caspase-1 and pyroptosis through the generation of excessive amount of caspase-1 protein. Mechanistically, DHA increased caspase-1 by specifically accelerating caspase-1 protein synthesis via the p38MAPK/Mnk1 signaling pathway. We have uncovered an unknown pyroptosis mechanism in which caspase-1-dependent pyroptosis can occur without the participation of ASC/inflammasome.

Clinical feature-based diagnosis criteria of eosinophil and non-eosinophil chronic rhinosinusitis in Taiwan.

Background: The prevalence of eosinophilic chronic rhinosinusitis (ECRS) has increased in Taiwan with a higher recurrence rate of nasal polyps after surgery. Therefore, we aimed to formulate the pre-operative diagnostic criteria for patients with ECRS in Taiwan. Methods: This case-control study included patients diagnosed with CRS with nasal polyps (CRSwNP) who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. The patients were classified into ECRS and non-eosinophilic CRS (NECRS) groups based on their histopathology. Demographic data, symptom severity scores, and computed tomography findings of the two groups were analyzed. We utilized receiver operating characteristic curve (ROC) analysis to evaluate parameters that could predict the diagnosis of ECRS. Results: Total 408 CRSwNP patients were enrolled (ECRS group: 163; NECRS group: 245). ECRS group was strongly associated with asthma (6.1% vs. 2.0%, p = .03), higher blood eosinophil counts (4.3% vs. 2.7%, p < .01), higher serum IgE (285.3 vs. 50.2 IU/mL, p = .02), and higher 22-item Sino-Nasal Outcome Test (SNOT-22) score (40.5 vs. 36.7, p = .03). The ECRS criteria based on ROC curve included the SNOT-22 (>45, 2 points), serum eosinophil count percentage (>4%, 4 points), asthma (4 points), total serum IgE (>140 IU/mL, 4 points), Lund-Mackay score (>9.5, 4 points), and ethmoid-to-maxillary opacification ratio on CT (>1.5, 5 points). The cutoff score was 14 points (sensitivity, 70.2%; specificity, 93.3%). Conclusions: Clinical-feature-based criteria may predict the diagnosis of ECRS before FESS in Taiwan. Level of Evidence: Level 3.