3D Printable Modular Soft Elastomers from Physically Cross-linked Homogeneous Associative Polymers.

Three-dimensional (3D) printing of elastomers enables the fabrication of many technologically important structures and devices. However, there remains a critical need for the development of reprocessable, solvent-free, soft elastomers that can be printed without the need for post-treatment. Herein, we report modular soft elastomers suitable for direct ink writing (DIW) printing by physically cross-linking associative polymers with a high fraction of reversible bonds. We designed and synthesized linear-associative-linear (LAL) triblock copolymers; the middle block is an associative polymer carrying amide groups that form double hydrogen bonding, and the end blocks aggregate to hard glassy domains that effectively act as physical cross-links. The amide groups do not aggregate to nanoscale clusters and only slow down polymer dynamics without changing the shape of the linear viscoelastic spectra; this enables molecular control over energy dissipation by varying the fraction of the associative groups. Increasing the volume fraction of the end linear blocks increases the network stiffness by more than 100 times without significantly compromising the extensibility. We created elastomers with Young's moduli ranging from 8 kPa to 8 MPa while maintaining the tensile breaking strain around 150%. Using a high-temperature DIW printing platform, we transformed our elastomers to complex, highly deformable 3D structures without involving any solvent or post-print processing. Our elastomers represent the softest melt reprocessable materials for DIW printing. The developed LAL polymers synergize emerging homogeneous associative polymers with a high fraction of reversible bonds and classical block copolymer self-assembly to form a dual-cross-linked network, providing a versatile platform for the modular design and development of soft melt reprocessable elastomeric materials for practical applications.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Circulating plasma cells as a predictive biomarker in Multiple myeloma: an updated systematic review and meta-analysis.

BACKGROUND: Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status. METHODS: The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software. RESULTS: Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81-2.66, p < 0.001) and PFS (HR = 2.45, 95% CI: 1.93-3.12, p < 0.001). Subgroup analyses did not alter the prognostic role of CPCs, regardless of region, sample size, cut-off value, detection time, initial treatment, or data type. Moreover, the increased CPCs were significantly related to advanced tumour stage (ISS III vs. ISS I-II: pooled OR = 2.89, 95% CI: 2.41-3.46, p < 0.001; R-ISS III vs. R-ISS I-II: pooled OR = 3.65, 95% CI: 2.43-5.50, p < 0.001) and high-risk cytogenetics (high-risk vs. standard-risk: OR = 2.22, 95% CI: 1.60-3.08, p < 0.001). CONCLUSION: Our meta-analysis confirmed that the increased number of CPCs had a negative impact on the PFS and OS of MM patients. Therefore, CPCs could be a promising prognostic biomarker that helps with risk stratification and disease monitoring.

There is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.Our meta-analysis revealed that a high CPCs level was significantly associated with worse OS and PFS in MM patients.CPCs could be a promising predictive biomarker that helps with risk stratification and disease monitoring.

The safety, feasibility and oncological outcomes of laparoscopic completion total gastrectomy for remnant gastric cancer: a prospective study with 3-year follow-up (FUGES-004 study).

BACKGROUND: The efficacy of laparoscopic completion total gastrectomy (LCTG) for remnant gastric cancer (RGC) remains controversial. METHODS: The primary outcome was postoperative morbidity within 30 days after surgery. Secondary outcomes included 3-year disease-free survival (DFS), 3-year overall survival (OS), and recurrence. Inverse probability treatment weighted (IPTW) was used to balance the baseline between LCTG and OCTG. RESULTS: Final analysis included 46 patients with RGC who underwent LCTG at the FJMUUH between June 2016 and June 2020. The historical control group comprised of 160 patients who underwent open completion total gastrectomy (OCTG) in the six tertiary teaching hospitals from CRGC-01 study. After IPTW, no significant difference was observed between the LCTG and OCTG groups in terms of incidence (LCTG vs. OCTG: 28.0% vs. 35.0%, P=0.379) or severity of complications within 30 days after surgery. Compared with OCTG, LCTG resulted in better short-term outcomes and faster postoperative recovery. However, the textbook outcome rate was comparable between the two groups (45.9% vs. 32.8%, P=0.107). Additionally, the 3-year DFS and 3-year OS of LCTG were comparable to those of OCTG (DFS: log-rank P=0.173; OS: log-rank P=0.319). No significant differences in recurrence type, mean recurrence time, or 3-year cumulative hazard of recurrence were observed between the two groups (all P>0.05). Subgroup analyses and concurrent comparisons demonstrated similar trends. CONCLUSIONS: This prospective study suggested that LCTG was non-inferior to OCTG in both short- and long-term outcomes. In experienced centers, LCTG may be considered as a viable treatment option for RGC.

CDC167 exhibits potential as a biomarker for airway inflammation in asthma.

Current asthma treatments have been discovered to decrease the risk of disease progression. Herein, we aimed to characterize novel potential therapeutic targets for asthma. Differentially expressed genes (DEGs) for GSE64913 and GSE137268 datasets were characterized. Weighted correlation network analysis (WGCNA) was used to identify trait-related module genes within the GSE67472 dataset. The intersection of the module genes of interest, as well as the DEGs, comprised the key module genes that underwent additional candidate gene screening using machine learning. In addition, a bioinformatics-based approach was used to analyze the relative expression levels, diagnostic values, and reverently enriched pathways of the screened candidate genes. Furthermore, the candidate genes were silenced in asthmatic mice, and the inflammation and lung injury in the mice were validated. A total of 1710 DEGs were characterized in GSE64913 and GSE137268 for asthma patients. WGCNA identified 2367 asthma module genes, of which 285 overlapped with 1710 DEGs. Four candidate genes, CDC167, POSTN, SEC14L1, and SERPINB2, were validated using the intersection genes of three machine learning algorithms, including Least Absolute Shrinkage and Selection Operator, Random Forest, and Support Vector Machine. All the candidate genes were significantly upregulated in asthma patients and demonstrated diagnostic utility for asthma. Furthermore, silencing CDC167 reduced the levels of inflammatory cytokines significantly and alleviated lung injury in ovalbumin (OVA)-induced asthmatic mice. Our study demonstrated that CDC167 exhibits potential as diagnostic markers and therapeutic targets for asthma patients.

An EEG Signature of MCH Neuron Activities Predicts Cocaine Seeking.

Background: Identifying biomarkers that predict substance use disorder (SUD) propensity may better strategize anti-addiction treatment. The melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) critically mediates interactions between sleep and substance use; however, their activities are largely obscured in surface electroencephalogram (EEG) measures, hindering the development of biomarkers. Methods: Surface EEG signals and real-time Ca2+ activities of LH MCH neurons (Ca2+MCH) were simultaneously recorded in male and female adult rats. Mathematical modeling and machine learning were then applied to predict Ca2+MCH using EEG derivatives. The robustness of the predictions was tested across sex and treatment conditions. Finally, features extracted from the EEG-predicted Ca2+MCH either before or after cocaine experience were used to predict future drug-seeking behaviors. Results: An EEG waveform derivative - a modified theta-to-delta ratio (EEG Ratio) - accurately tracks real-time Ca2+MCH in rats. The prediction was robust during rapid eye movement sleep (REMS), persisted through REMS manipulations, wakefulness, circadian phases, and was consistent across sex. Moreover, cocaine self-administration and long-term withdrawal altered EEG Ratio suggesting shortening and circadian redistribution of synchronous MCH neuron activities. In addition, features of EEG Ratio indicative of prolonged synchronous MCH neuron activities predicted lower subsequent cocaine seeking. EEG Ratio also exhibited advantages over conventional REMS measures for the predictions. Conclusions: The identified EEG Ratio may serve as a non-invasive measure for assessing MCH neuron activities in vivo and evaluating REMS; it may also serve as a potential biomarker predicting drug use propensity.

Infant Formulas With Partially or Extensively Hydrolyzed Milk Proteins for the Prevention of Allergic Diseases: A Systematic Review and Meta-Analysis of Clinical Trials.

Despite the widely recommended usage of partially hydrolyzed formula (PHF) or extensively hydrolyzed formula (EHF) of milk protein for preventing allergic diseases (ADs), clinical studies have been inconclusive regarding their efficacy compared with that of cow milk formula (CMF) or breast milk (BM). We aimed to systematically evaluate the effects of PHF or EHF compared with those of CMF or BM on risk of ADs (cow milk allergy, allergic rhinitis, eczema, asthma, wheeze, food allergy, and sensitization) in children. We searched PubMed, Embase, Cochrane Library, and Web of Science for clinical trials published from inception to 21 October, 2022. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to grade the strength of evidence. Overall, 24 trials (10,950 infants) were included, 17 of which specifically included high-risk infants. GRADE was low for the evidence that, compared with CMF, infants early fed with EHF had lower risk of cow milk allergy at age 0-2 y [relative risk (RR): 0.62; 95% CI: 0.39, 0.99]. Moderate evidence supported that PHF and EHF reduced risk of eczema in children aged younger or older than 2 y, respectively (RR: 0.71; 95% CI: 0.52, 0.96; and RR: 0.79; 95% CI: 0.67, 0.94, respectively). We also identified moderate systematic evidence indicating that PHF reduced risk of wheeze at age 0-2 y compared with CMF (RR: 0.50; 95% CI: 0.29, 0.85), but PHF and EHF increased the risk compared with BM (RR: 1.61; 95% CI: 1.11, 2.31; and RR: 1.64; 95% CI: 1.26, 2.14). Neither PHF nor EHF had significant effects on other ADs in children of any age. In conclusion, compared with CMF, PHF, or EHF had different preventive effect on cow milk allergy, eczema, and wheeze. Compared with BM, both PHF and EHF may increase risk of wheeze but not other ADs. Given that most trials included only high-risk infants, more research on non-high-risk infants is warranted before any generalization is attempted. This protocol was registered at PROSPERO as CRD42022320787.

The Associations of Prenatal Exposure to Fine Particulate Matter and Its Chemical Components with Allergic Rhinitis in Children and the Modification Effect of Polyunsaturated Fatty Acids: A Birth Cohort Study.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have been shown to protect against fine particulate matter <2.5µm in aerodynamic diameter (PM2.5)-induced hazards. However, limited evidence is available for respiratory health, particularly in pregnant women and their offspring. OBJECTIVES: We aimed to investigate the association of prenatal exposure to PM2.5 and its chemical components with allergic rhinitis (AR) in children and explore effect modification by maternal erythrocyte PUFAs. METHODS: This prospective birth cohort study involved 657 mother-child pairs from Guangzhou, China. Prenatal exposure to residential PM2.5 mass and its components [black carbon (BC), organic matter (OM), sulfate (SO42-), nitrate (NO3-), and ammonium (NH4+)] were estimated by an established spatiotemporal model. Maternal erythrocyte PUFAs during pregnancy were measured using gas chromatography. The diagnosis of AR and report of AR symptoms in children were assessed up to 2 years of age. We used Cox regression with the quantile-based g-computation approach to assess the individual and joint effects of PM2.5 components and examine the modification effects of maternal PUFA levels. RESULTS: Approximately 5.33% and 8.07% of children had AR and related symptoms, respectively. The average concentration of prenatal PM2.5 was 35.50±5.31 µg/m3. PM2.5 was positively associated with the risk of developing AR [hazard ratio (HR)=1.85; 95% confidence interval (CI): 1.16, 2.96 per 5 µg/m3] and its symptoms (HR=1.79; 95% CI: 1.22, 2.62 per 5 µg/m3) after adjustment for confounders. Similar associations were observed between individual PM2.5 components and AR outcomes. Each quintile change in a mixture of components was associated with an adjusted HR of 3.73 (95% CI: 1.80, 7.73) and 2.69 (95% CI: 1.55, 4.67) for AR and AR symptoms, with BC accounting for the largest contribution. Higher levels of n-3 docosapentaenoic acid and lower levels of n-6 linoleic acid showed alleviating effects on AR symptoms risk associated with exposure to PM2.5 and its components. CONCLUSION: Prenatal exposure to PM2.5 and its chemical components, particularly BC, was associated with AR/symptoms in early childhood. We highlight that PUFA biomarkers could modify the adverse effects of PM2.5 on respiratory allergy. https://doi.org/10.1289/EHP13524.

Attachment of various-shaped polystyrene microplastics to silica surfaces: Experimental validation of the equivalent Cassini oval extended DLVO model.

Microplastics (MPs) vary in shape and surface characteristics in the environment. The attachment of MPs to surfaces can be studied using the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. However, this theory does not account for the shape MPs. Therefore, we investigated the attachment of spherical, pear-shaped, and peanut-shaped polystyrene MPs to quartz sand in NaCl and CaCl2 solutions using batch tests. The attachment of MPs to quartz sand was quantified using the attachment efficiency (alpha). Subsequently, alpha behaviors were interpreted using energy barriers (EBs) and interaction minima obtained from extended DLVO calculations, which were performed using an equivalent sphere model (ESM) and a newly developed equivalent Cassini model (ECM) to account for the shape of the MPs. The ESM failed to interpret the alpha behavior of the three MP shapes because it predicted high EBs and shallow minima. The alpha values for spherical MPs (0.62-1.00 in NaCl and 0.48-0.96 in CaCl2) were higher than those for pear- and peanut-shaped MPs (0.01-0.63 in NaCl and 0.02-0.46 in CaCl2, and 0.01-0.59 in NaCl and 0.02-0.40 in CaCl2, respectively). Conversely, the ECM could interpret the alpha behavior of pear- and peanut-shaped MPs either by changes in EBs or interaction minima as a function of orientation angles and electrolyte ionic strength. Therefore, the particle shape must be considered to improve the attachment analyses.

The non-linear relationship between serum albumin and diabetic retinopathy in type 2 diabetes mellitus: a secondary analysis based on a cross-sectional study.

BACKGROUND: Most studies had shown a linear relationship between serum albumin (sALB) and the prevalence of diabetic retinopathy (DR). Thus, the purpose of this study is to investigate whether their relationship is non-linear. METHODS: We included 426 patients with type 2 diabetes who were hospitalized in Guangdong Provincial People's Hospital from December 2017 to November 2018. The outcome was the prevalence of DR. A two-piecewise logistics regression model was performed to identify the non-linear relationship between sALB and the prevalence of DR. The inflection point was calculated to determine the saturation effect through the maximum likelihood ratio and a recursive algorithm. RESULTS: DR was diagnosed in 167 of 426 type 2 diabetic patients. The relationship between sALB and DR was nonlinear. When sALB was less than 38.10 g/L, a significant negative association was observed (OR = 0.82; 95% CI, 0.72-0.94; P = 0.0037), while no significant association was observed when sALB was greater than 38.10 g/L (OR = 1.12; 95% CI, 0.92-1.35; P = 0.2637). CONCLUSIONS: The relationship between sALB and the prevalence of DR is non-linear. sALB is negatively associated with the prevalence of DR when sALB is less than 38.10 g/L. Our findings need to be confirmed by further prospective research.

[Potential Ecological Risk Characteristics and Source Apportionment of Heavy Metals in Farmland Soils around Typical Factories in Hunan Province Based on Monte-Carlo Simulation].

In order to explore the pollution characteristics， ecological risks， and pollution sources of heavy metals in farmland soils around typical factories in Hunan Province， the content characteristics of eight heavy metals in farmland soils around fluoride factories， leather factories， and plating plants were analyzed. The geo-accumulation index and potential ecological risk index were used to evaluate the pollution and environmental risk of heavy metals. The correlation analysis， hierarchical cluster analysis， and principal component analysis were used to analyze the sources of heavy metals. The Monte-Carlo model was used to evaluate the probability risk of regional ecological risk. The results showed that the main pollution elements in the soil were Cd and Zn， and their mean values were 4.46 and 2.73 times the background values， respectively. Zn was at a mild pollution level in the soil of the three typical factories， and Cd was at a moderate pollution level in the whole fluoride factory. The pollution sources of heavy metals in the typical factories were mainly natural sources， industrial activity sources （industrial waste discharge， mineral mining， and smelting activities）， traffic sources， etc. The results of potential ecological risk assessment showed that the ecological risk of the fluoride factory was at a high risk level， and the ecological risk of the leather factory and plating plants was at a high risk level. Cd was the main contributing element. The results of Monte-Carlo probabilistic ecological risk assessment reduced the uncertainty of deterministic assessment， which could provide scientific basis for accurate risk management and control in the regions.

Prevalence and influencing factors of kinesiophobia in older patients with primary osteoporosis: A cross-sectional survey.

AIM: To explore the prevalence of kinesiophobia in older patients with primary osteoporosis and analyze its influencing factors. METHODS: A cross-sectional survey was conducted among 221 older patients with primary osteoporosis in a general hospital in Kunming, China. Data were collected through a sociodemographic-clinical questionnaire, Tampa Scale for Kinesiophobia-11 (TSK-11), Global Pain Scale (GPS), Five Facets Mindfulness Questionnaire-Short Form (FFMQ-SF), and Hospital Anxiety and Depression Scale (HADS). SPSS 27.0 software was utilized for univariate and binary logistic regression analyses. RESULTS: The findings revealed that the prevalence of kinesiophobia in this study was 57.01 %. Age, history of fractures, chronic obstructive pulmonary disease (COPD), lumbar disc herniation, chronic pain, mindfulness, anxiety, and depression were identified as significant influencing factors of kinesiophobia in the binary logistic regression analyses. CONCLUSION: Healthcare professionals should be attentive to occurrence of kinesiophobia. Timely measures should be implemented to improve pain, anxiety and depression, and employ mindfulness interventions to mitigate kinesiophobia.

Multimodal Spectroscopic Studies to Evaluate the Effect of Nod-Factor-Based Fertilizer on the Maize (Zea mays) Stem.

Maize (Zea mays) is one of the most cultivated plants in the world. Due to the large area, the scale of its production, and the demand to increase the yield, there is a need for new environmentally friendly fertilizers. One group of such candidates is bacteria-produced nodulation (or nod) factors. Limited research has explored the impact of nodulation, factors on maize within field conditions, with most studies restricted to greenhouse settings and early developmental stages. Additionally, there is a scarcity of investigations that elucidate the metabolic alterations in the maize stem due to nod-factor exposure. It was therefore the aim of this study. Maize stem's metabolites and fibers were analyzed with various imaging analytical techniques: matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI), Raman spectroscopy, attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR), and diffuse reflectance infrared Fourier transform spectroscopy. Moreover, the biochemical analyses were used to evaluate the proteins and soluble carbohydrates concentration and total phenolic content. These techniques were used to evaluate the influence of nod factor-based biofertilizer on the growth of a non-symbiotic plant, maize. The biofertilizer increased the grain yield and the stem mass. Moreover, the spectroscopic and biochemical investigation proved the appreciable biochemical changes in the stems of the maize in biofertilizer-treated plants. Noticeable changes were found in the spatial distribution and the increase in the concentration of flavonoids such as maysin, quercetin, and rutin. Moreover, the concentration of cell wall components (fibers) increased. Furthermore, it was shown that the use of untargeted analyses (such as Raman and ATR FT-IR, spectroscopic imaging, and MALDI-MSI) is useful for the investigation of the biochemical changes in plants.

Self-Assembly of Amphiphilic PDI and NDI Derivatives with Opposite Thermoresponsive Fluorescent Behaviors in Aqueous Solution.

This work presents a study of the thermally induced aggregation of perylene diimide (PDI) and naphthalene diimide (NDI) derivatives modified with oligo ethylene glycol (OEG) chains in aqueous solution. Water-soluble and flexible OEG side chains were introduced into the π-core of glutamate-modified NDI and PDI structures, and the aggregation process was modulated by heating or cooling in water. Interestingly, a rare opposite temperature response of fluorescent behavior from the two amphiphilic chromophores was revealed, in which the PDI exhibited fluorescent enhancement, while fluorescent quenching upon temperature increase was observed from the NDI assembly. The mechanism of thermally induced aggregation is clearly explained by studies with various spectroscopic techniques including UV-visible, fluorescence, 1H NMR, 2D NMR spectroscopy, and SEM observation as well as control experiments operated in DMSO solution. It is found that although similar J-aggregates were formed by both amphiphilic chromophores in aqueous solution, the temperature response of the aggregates to temperature was opposite. The degree of PDI aggregation decreased, while that of NDI increased upon temperature rising. This research paves a valuable way for understanding the complicated supramolecular behaviors of amphiphilic chromophores.

Effects of solution chemistry on dielectric barrier atmospheric non-thermal plasma for operative degradation of antiretroviral drug nevirapine.

The global prevalence of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has been an environmental menace. Tons of drug wastes from antiretroviral therapy are released into the environment annually. We, for the first time, employed the novel dielectric barrier atmospheric non-thermal plasma (DBANP) discharge, to mitigate the inadvertent pollution arising from the antiretroviral therapy. A 40-min treatment of nevirapine achieved >94 % (0.075 min-1) removal efficiency at discharge power of 63.5 W and plasma working gas of atmospheric air. Chemical probes confirmed •OH, ONOO- and eaq- as the dominant reactive species whilst further revealing the reaction acceleration role of NaNO3 and CCl4 which are known reaction terminators. The commonly coexisting inorganic anions potentiated nevirapine removal with over 98 % efficiency, achieving the highest rate constant of 0.148 min-1 in this study. Moreover, the initial solution pH (1.5-11.1) was no limiting factor either. The insensitivity of the DBANP discharge to actual water matrices was an eminent inference of its potential applicability in practical conditions. With reference to data obtained from the liquid chromatography-mass spectrometer analysis, nevirapine degradation pathway was proposed. A nucleophilic attack by ONOO- at the cyclopropyl group and •OH attack at the carbonyl carbon of the amide group, respectively, initiated nevirapine degradation process. It is anticipated that the findings herein, will provide new insights into antiretroviral drug waste management in environmental waters using the innovative and green non-thermal plasma process.

Shikonin suppresses rheumatoid arthritis by inducing apoptosis and autophagy via modulation of the AMPK/mTOR/ULK-1 signaling pathway.

BACKGROUND: The overproliferation of fibroblast-like synoviocytes (FLS) contributes to synovial hyperplasia, a pivotal pathological feature of rheumatoid arthritis (RA). Shikonin (SKN), the active compound from Lithospermum erythrorhizon, exerts anti-RA effects by diverse means. However, further research is needed to confirm SKN's in vitro and in vivo anti-proliferative functions and reveal the underlying specific molecular mechanisms. PURPOSE: This study revealed SKN's anti-proliferative effects by inducing both apoptosis and autophagic cell death in RA FLS and adjuvant-induced arthritis (AIA) rat synovium, with involvement of regulating the AMPK/mTOR/ULK-1 pathway. METHODS: SKN's influences on RA FLS were assessed for proliferation, apoptosis, and autophagy with immunofluorescence staining (Ki67, LC3B, P62), EdU incorporation assay, staining assays of Hoechst, Annexin V-FITC/PI, and JC-1, transmission electron microscopy, mCherry-GFP-LC3B puncta assay, and western blot. In AIA rats, SKN's anti-arthritic effects were assessed, and its impacts on synovial proliferation, apoptosis, and autophagy were studied using Ki67 immunohistochemistry, TUNEL, and western blot. The involvement of AMPK/mTOR/ULK-1 pathway was examined via western blot. RESULTS: SKN suppressed RA FLS proliferation with reduced cell viability and decreased Ki67-positive and EdU-positive cells. SKN promoted RA FLS apoptosis, as evidenced by apoptotic nuclear fragmentation, increased Annexin V-FITC/PI-stained cells, reduced mitochondrial potential, elevated Bax/Bcl-2 ratio, and increased cleaved-caspase 3 and cleaved-PARP protein levels. SKN also enhanced RA FLS autophagy, featuring increased LC3B, reduced P62, autophagosome formation, and activated autophagic flux. Autophagy inhibition by 3-MA attenuated SKN's anti-proliferative roles, implying that SKN-induced autophagy contributes to cell death. In vivo, SKN mitigated the severity of rat AIA while also reducing Ki67 expression, inducing apoptosis, and enhancing autophagy within AIA rat synovium. Mechanistically, SKN modulated the AMPK/mTOR/ULK-1 pathway in RA FLS and AIA rat synovium, as shown by elevated P-AMPK and P-ULK-1 expression and decreased P-mTOR expression. This regulation was supported by the reversal of SKN's in vitro and in vivo effects upon co-administration with the AMPK inhibitor compound C. CONCLUSION: SKN exerted in vitro and in vivo anti-proliferative properties by inducing apoptosis and autophagic cell death via modulating the AMPK/mTOR/ULK-1 pathway. Our study revealed novel molecular mechanisms underlying SKN's anti-RA effects.

Policies and Practices Regarding Preparative Fasting for Contrast-Enhanced Computed Tomography: A Nationwide Survey.

OBJECTIVES: To evaluate current policies and practices regarding preparative fasting before contrast-enhanced computed tomography (CECT) and the knowledge and attitudes of radiology head nurses. METHODS: Radiology head nurses in 499 Chinese hospitals participated in an online survey on preparative fasting for CECT, which mainly included current departmental policies and practices and their knowledge and attitudes. RESULTS: Response rate was 89.8% (448/499). All surveyed hospitals established preparative fasting protocols, mainly based on guidelines for iodinated contrast media (ICM) usage (68.8%). For the nongastrointestinal CECT scan, the most frequent fasting duration for solid food, semiliquid diet, liquid diet, and clear liquids was 4 to 6 hours (215/422 [50.9%]), less than 6 hours (332/396 [83.8%]), less than 6 hours (275/320, 85.9%), and less than 6 hours (151/189 [79.9%]), respectively. Forty-six percent of the respondents confirmed that unnecessary excessive fasting existed in practice, and the related patient discomfort occurred in 60.3% of the hospitals, mainly manifested as hypoglycemia (86.7%). Expert consensus and guidelines for iodinated contrast media usage (75%) were the leading approach to gain knowledge about preparative fasting; 90.6% of the respondents believed that the clinical scenarios requiring preparative fasting were the upper abdominal examinations. A majority of respondents (72.1%) believed that the current preparative fasting policies needed improvement. CONCLUSION: Preparative fasting policies varied among hospitals in terms of the fasting content and duration. Respondents' opinions differed on fasting requirements based on various CECT examination sites and patients. The latest guideline regarding no fasting before CECT has not been fully adopted. Further research is required to promote the transformation of guideline evidence.

Protective effects of piperlongumine against adjuvant-induced arthritis in rats through modulating OPG/RANKL/NF-κB signaling pathway.

OBJECTIVES: We examined the antirheumatoid effects of piperlongumine (PLM) on rat adjuvant-induced arthritis (AIA) and explored the underlying mechanisms involved. METHODS: PLM (2.5, 5, and 10 mg/kg) was administered intraperitoneally to AIA rats to assess its effectiveness. Blood, thymus, spleen, ankle joint, and synovial tissue samples were gathered for subsequent analyses, like enzyme-linked immunosorbent assay, thymus/spleen index measurement, ankle joint pathological examination, immunohistochemistry assay, polymerase chain reaction, and western blot assay. Moreover, the involvement of osteoprotegerin (OPG)/receptor activators of nuclear factor κB ligand (RANKL)/nuclear factor-κB (NF-κB) signaling was investigated. KEY FINDINGS: PLM effectively relieved inflammation and joint destruction in AIA rats, as indicated by reductions in hind paw swelling, arthritis index, thymus/spleen index, ankle joint pathological damage, production of TNF-α, IL-1ß, and IL-6 in both serum and synovium, and osteoclast formation. Also, PLM treatment raised OPG production, reduced RANKL expression, and elevated the OPG/RANKL ratio in synovial tissues. Furthermore, PLM prevented IκBα degradation and phosphorylation, resulting in a reduced expression of the nuclear NF-κB p65 protein in AIA rat synovial tissues. CONCLUSIONS: PLM demonstrated strong antiarthritic effects in rats with AIA by influencing the OPG/RANKL/NF-κB signaling pathway, highlighting its potential clinical relevance in treating rheumatoid arthritis.

Removal of per- and polyfluoroalkyl substances from water by plasma treatment: Insights into structural effects and underlying mechanisms.

Non-thermal plasma emerges as a promising technology for per- and polyfluoroalkyl substances (PFAS) decomposition due to its notable efficacy and environmentally friendly characteristics. In this study, we demonstrated the efficacy of a falling film dielectric barrier discharge (DBD) system for the removal of 10 PFAS, including perfluoroalkyl carboxylic acids (PFCAs), perfluoroalkyl sulfonic acids (PFSAs) and hexafluoropropylene oxide (HFPO) oligomer acids. Results showed that compounds with fluoroalkyl chain length>4 were effectively decomposed within 100 min, with long-chain PFAS demonstrating more pronounced removal performance than their short-chain analogues. The superior removal but low defluorination observed in HFPO oligomer acids could be ascribed to their ether-based structural features. The integration of experimental results with density functional theory (DFT) calculations revealed that the synergistic effects of various reactive species are pivotal to their efficient decomposition, with electrons, OH•, and NO2• playing essential roles. In contrast, the degradation of PFSAs was more dependent on electron attack than that of PFCAs and HFPO oligomer acids. Significantly, the most crucial degradation pathway for HFPO oligomer acids was the cleavage of ether CO, whether through radical or electron attack. Furthermore, the demonstrated effective removal in various water matrices showed the potential of the plasma system for removing PFAS in complex aquatic environments. This study provided mechanistic insights into PFAS degradation behavior in plasma processes, and it underscored the vital influence of molecular structures on degradability, thereby contributing to the further development and regulation of plasma-based technologies for treating PFAS in water.

Decreased transport of nano- and micro-plastics in the presence of low-molecular-weight organic acids in saturated quartz sand.

Low-molecular-weight organic acids (LMWOAs) and nano- and micro-plastics (NPs and MPs) are both widely distributed in terrestrial systems. To better understand the influence of LMWOAs on the transport of NPs and MPs, the effects of 0.5 mM citric- (CA), malic- (MA), and tartaric- (TA) acid on the transport of nano- (0.51 µm, PS NPs) and micro- (1.1 µm, PS MPs) polystyrene particles (2 mg L-1) in saturated quartz sand were investigated. All three LMWOAs decreased the transport of PS NPs and MPs, regardless of ionic composition or strength (0.1-10 mM NaCl and 0.1-1 mM CaCl2). Further investigation revealed that the interfacial interactions between PS-quartz sand surfaces and PS-PS were altered by LMWOAs. LMWOAs adsorbed to quartz sand surfaces could serve as new deposition sites, as evidenced by the decreased transport of PS NPs and MPs in quartz sand that was subjected to pre-equilibration with selected MA, the low inhibition of PS transport with low concentrations of LMWOAs (0.1 mM), and also the adsorption of LMWOAs onto quartz sand surfaces by batch experiments. Meanwhile, the adsorption of LMWOAs on PS, hydrodynamic measurement and visual TEM observation together clarified the slight aggregation of PS NPs and MPs in suspensions, inducing the subsequent decrease in transport. Among them, the adsorption of LMWOAs onto quartz sand surfaces was found to be the main factor dominating the decreased transport of both PS NPs and MPs in saturated quartz sand.