Functionalized nano cellulose double-template imprinted aerogel microsphere for the targeted enrichment of taxanes.

Paclitaxel, a diterpenoid isolated from the bark of Taxus wallichiana var. chinensis (Pilger) Florin, is currently showing significant therapeutic effects against a variety of cancers. Baccatin III (Bac) and 10-Deacetylbaccatin III (10-DAB) are in great demand as important precursors for the synthesis of paclitaxel. This work aims to develop a simple, rapid and highly selective, safe, and non-polluting molecularly imprinted material for 10-DAB and Bac enrichment. In this study, we innovatively prepared molecularly imprinted materials with nanocellulose aerogel microspheres and 2-vinylpyridine (2-VP) as a bifunctional monomer, and 10-DAB and Bac as bis-template molecules. In particular, functionalized nanocellulose dual-template molecularly imprinted aerogel microsphere (FNCAG-DMIM) were successfully synthesized by the bifunctional introduction of functional nanocellulose aerogel microsphere (FNCAG) modified with Polyethyleneimine (PEI) as a carrier and functional monomer, which provided a large number of recognition sites for bimodal molecules. FNCAG-DMIM showed high specificity for 10-DAB and Bac specific assays. Under the optimal experimental conditions, the adsorption capacities of FNCAG-DMIM for 10-DAB and Bac reached 52.27 mg g-1 and 53.81 mg g-1, respectively. In addition, it showed good reliability and practicality in the determination of real samples. The present study extends the research on the synthesis of natural functional monomers by molecularly imprinted materials and opens up new horizons for the targeted isolation of plant compounds by dual-template molecularly imprinted materials.

Persistent organic pollutants in feathers of various terrestrial and aquatic bird species: Interspecies difference and source apportionment.

Feathers are regarded as important nondestructive biomonitoring tools for bird pollutants. However, external contamination of feathers by different pollutants in different bird species remains unclear. In the present study, the feathers of 16 bird species, including terrestrial, freshwater, and marine birds, were analyzed for persistent organic pollutants (POPs). Bird feathers from an abandoned e-waste recycling site had higher POP concentrations and were more correlated with the POP muscle concentrations than those from the less polluted areas. The significant and positive POP correlations between the feathers and muscles of different species indicate that feathers are a good indicator of inter-species and spatial pollution. For individual species, the most hydrophobic POPs in feathers, such as hepta- to deca-polybrominated diphenyl ethers, had higher proportions than in muscles and worse correlations with muscle POPs compared with other POPs. Results of the chemical mass balance (CMB) model revealed that the gaseous phase, internal pollution, and atmospheric particle phase were the main contributors to low-, medium-, and high-hydrophobicity POPs in feathers, respectively. Overall, this study provides a preliminary but meaningful framework for distinguishing between internal and external contamination in feathers and gives information concerning the fitness of feathers as POP indicators with specific physicochemical properties.

LNCHC directly binds and regulates YBX1 stability to ameliorate metabolic dysfunction-associated steatotic liver disease progression.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the foremost cause of chronic liver disease, yet its underlying mechanisms remain elusive. Our group previously discovered a novel long non-coding RNA (lncRNA) in rats, termed lncHC and its human counterpart, LNCHC. This study aimed to explore the role of LNCHC in the progression of MASLD. METHODS: RNA-binding proteins bound to LNCHC were searched by mass spectrometry. The target genes of LNCHC and Y-Box binding protein 1 (YBX1) were identified by RNA-seq. MASLD animal models were utilised to examine the roles of LNCHC, YBX1 and patatin-like phospholipase domain containing 3 (PNPLA3) in MASLD progression. RESULTS: Here, we identified LNCHC as a native restrainer during MASLD development. Notably, LNCHC directly binds YBX1 and prevents protein ubiquitination. Up-regulation of YBX1 then stabilises PNPLA3 mRNA to alleviate lipid accumulation in hepatocytes. Furthermore, both cell and animal studies demonstrate that LNCHC, YBX1 and PNPLA3 function to improve hepatocyte lipid accumulation and exacerbate metabolic dysfunction-associated steatohepatitis development. CONCLUSIONS: In summary, our findings unveil a novel LNCHC functionality in regulating YBX1 and PNPLA3 mRNA stability during MASLD development, providing new avenues in MASLD treatment.

Focus on the cGAS-STING Signaling Pathway in Sepsis and Its Inflammatory Regulatory Effects.

Sepsis is a severe systemic inflammatory response commonly occurring in infectious diseases, caused by infection with virulent pathogens. In the pathogenesis of sepsis, the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway serves a crucial role as a fundamental immunoregulatory mechanism. This signaling pathway activates STING upon recognizing intracellular DNA damage and pathogen-derived DNA, subsequently inducing the production of numerous inflammatory mediators, including interferon and inflammatory cytokines, which in turn trigger an inflammatory response. The aim of this paper is to explore the activation mechanism of the cGAS-STING signaling pathway in sepsis and its impact on inflammatory regulation. By delving into the mechanism of action of the cGAS-STING signaling pathway in sepsis, we aim to identify new therapeutic strategies for the treatment and prevention of sepsis.

Enhanced catalytic activity of Fe3O4-carbon dots complex in the Fenton reaction for enhanced immunotherapeutic and oxygenation effects.

Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe3O4-carbon dots complex (Fe3O4-CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe3O4-CDs@Fc nano complex. The CDs catalyzed the Fenton reaction activity of Fe3O4 by helping to improve the electron transfer efficiency, extended the reaction pH condition to 7.4. The Fe3O4-CDs@Fc exhibit exceptional optical activity, achieving a thermal conversion efficiency of 56.43 % under 808 nm light and a photosensitive single-line state oxygen quantum yield of 33 % under 660 nm light. Fe3O4-CDs@Fc improved intracellular oxygen level and inhibited hypoxia-inducing factor (HIF-1α) by in-situ oxygen production based on Fenton reaction. The multimodal combination of Fe3O4-CDs@Fc (CDT/PDT/PTT) strongly induced immune cell death (ICD). The expression of immune-related protein and HIF-1α was investigated by immunofluorescence method. In vivo, Fe3O4-CDs@Fc combined with immune checkpoint blocker (antibody PD-L1, αPD-L1) effectively ablated primary tumors and inhibited distal tumor growth. Fe3O4-CDs@Fc is a promising immune-antitumor drug.

Anti-Colon Cancer Activity of Copper-Doped Folate Carbon Dots/MnO2 Complexes Based on Oxygenation and Immune-Enhancing Effects.

In clinical practice, the treatment of colon cancer is faced with the dilemma of metastasis and recurrence, which is related to immunosuppression and hypoxia. Immune checkpoint blockade (ICB) is a negative regulatory pathway of immunity. Immune checkpoint blockade (ICB) is an important immunotherapy method. However, inadequate immunogenicity reduces the overall response rate of ICB. In this study, a tumor microenvironment-responsive nanomedicine (Cu-FACD@MnO2@FA) was prepared to increase host immune response and increase intracellular oxygen levels. Cu-FACD@MnO2@FA preferentially enriched at the tumor site, combined with the immune checkpoint inhibitor alpha PD-L1, induced sufficient immunogenicity to treat colon cancer. Immunofluorescence detection of tumor cells and tissues showed that the expression of hypoxa-inducing factor 1α was significantly down-regulated after treatment and the expression of immunoactivity-related proteins was significantly changed. In vivo treatment in a bilateral tumor mouse model showed complete ablation of the primary tumor and efficient inhibition of the distal tumor. In this study, for the first time, the oxygenation effects of MnO2-coated Cu-doped carbon dots and chemodynamic therapy and a strategy of combining with immuno-blocking therapy were used for treating colon cancer.

The network structures of depressive and insomnia symptoms among cancer patients using propensity score matching: Findings from the Health and Retirement Study (HRS).

OBJECTIVE: Both depression and insomnia are found to be more prevalent in cancer patients compared to the general population. This study compared the network structures of depression and insomnia among cancer patients versus cancer-free participants (controls hereafter). METHOD: The 8-item Center for Epidemiological Studies Depression Scale (CESD-8) and the 4-item Jenkins Sleep Scale (JSS-4) were used to measure depressive and insomnia symptoms, respectively. Propensity score matching (PSM) was used to construct the control group using data from the Health and Retirement Study (HRS). In total, a sample consisting of 2216 cancer patients and 2216 controls was constructed. Central (influential) and bridge symptoms were estimated using the expected influence (EI) and bridge expected influence (bridge EI), respectively. Network stability was assessed using the case-dropping bootstrap method. RESULT: The prevalence of depression (CESD-8 total score ≥ 4) in cancer patients was significantly higher compared to the control group (28.56 % vs. 24.73 %; P = 0.004). Cancer patients also had more severe depressive symptoms relative to controls, but there was no significant group difference for insomnia symptoms. The network structures of depressive and insomnia symptoms were comparable between cancer patients and controls. "Felt sadness" (EI: 6.866 in cancer patients; EI: 5.861 in controls), "Felt unhappy" (EI: 6.371 in cancer patients; EI: 5.720 in controls) and "Felt depressed" (EI: 6.003 in cancer patients; EI: 5.880 in controls) emerged as the key central symptoms, and "Felt tired in morning" (bridge EI: 1.870 in cancer patients; EI: 1.266 in controls) and "Everything was an effort" (bridge EI: 1.046 in cancer patients; EI: 0.921 in controls) were the key bridge symptoms across both groups. CONCLUSION: Although cancer patients had more frequent and severe depressive symptoms compared to controls, no significant difference was observed in the network structure or strength of the depressive and insomnia symptoms. Consequently, psychosocial interventions for treating depression and insomnia in the general population could be equally applicable for cancer patients who experience depression and insomnia.

Immunogenic Cell Death Induction and Oxygenation by Multifunctional Hollow Silica/Copper-Doped Carbon Dots.

The metastasis and recurrence of cancer are related to immunosuppression and hypoxia in the tumor microenvironment. Activating immune activity and improving the hypoxic environment face essential challenges. This paper reports on a multifunctional nanomaterial, HSCCMBC, that induces immunogenic cell death through powerful photodynamic therapy/chemodynamic therapy synergistic antitumor effects. The tumor microenvironment changed from the immunosuppressive type to immune type, activated the immune activity of the system, decomposed hydrogen peroxide to generate oxygen based on Fenton-like reaction, and effectively increased the level of intracellular O2 with the assistance of 3-bromopyruvate, a cell respiratory inhibitor. The structure and composition of HSCCMBC were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, infrared spectroscopy, etc. Oxygen probe RDPP was used to investigate the oxygen level inside and outside the cell, and hydroxyl radical probe tetramethylbenzidine was used to investigate the Fenton-like reaction ability. The immunofluorescence method investigated the expression of various immune markers and hypoxia-inducing factors in vitro and in vivo after treatment. In vitro and in vivo experiments indicate that HSCCMBC is an excellent antitumor agent and is expected to be a candidate drug for antitumor immunotherapy.

Downregulated GPX4 in salivary gland epithelial cells contributes to salivary secretion dysfunction in Sjogren's syndrome via lipid ROS/pSTAT4/AQP5 axis.

Sjogren's syndrome (SS) is an autoimmune disease characterized by dysfunction of exocrine glands, such as salivary glands. However, the molecular mechanism of salivary secretion dysfunction in SS is still unclear. Given the significance of glutathione peroxidase 4 (GPX4) in cellular redox homeostasis, we hypothesized that dysregulation of GPX4 may play a pivotal role in the pathogenesis of salivary secretion dysfunction observed in SS. The salivary gland of SS patients and the SS mouse model exhibited reduced expression of the ferroptosis inhibitor GPX4 and the important protein aquaporin 5 (AQP5), which is involved in salivary secretion. GPX4 overexpression upregulated and GPX4 knockdown downregulated AQP5 expression in salivary gland epithelial cells (SGECs) and salivary secretion. Bioinformatics analysis of GSE databases from SS patients' salivary glands revealed STAT4 as a key intermediary regulator between GPX4 and AQP5. A higher level of nuclear pSTAT4 was observed in the salivary gland of the SS mouse model. GPX4 overexpression inhibited and GPX4 knockdown promoted STAT4 phosphorylation and nuclear translocation in SGECs. CHIP assay confirmed the binding of pSTAT4 within the promoter of AQP5 inhibiting AQP5 transcription. GPX4 downregulation accumulates intracellular lipid ROS in SGECs. Lipid ROS inhibitor ferrostatin-1 treatment during in vitro and in vivo studies confirmed that lipid ROS activates STAT4 phosphorylation and nuclear translocation in SGECs. In summary, the downregulated GPX4 in SGECs contributes to salivary secretion dysfunction in SS via the lipid ROS/pSTAT4/AQP5 axis. This study unraveled novel targets to revitalize the salivary secretion function in SS patients.

Perioperative Adjunctive Esketamine for Postpartum Depression Among Women Undergoing Elective Cesarean Delivery: A Randomized Clinical Trial.

Importance: Postpartum depression (PPD) is one of the most common mental health conditions during the perinatal and postpartum periods, which can have adverse effects on both mother and infant. Objective: To investigate the efficacy of perioperative adjunctive esketamine administration after cesarean deliveries in the prevention of PPD. Design, Setting, and Participants: A single-center, double-blind, placebo-controlled, randomized clinical trial was conducted from January 1, 2022, to January 1, 2023, at Fujian Provincial Hospital among 298 women aged 18 to 40 years, with an American Society of Anesthesiologists grade I to III classification and singleton full-term pregnancies who were scheduled for elective cesarean deliveries. Primary analyses were performed on a modified intention-to-treat basis. Interventions: Patients were randomly assigned to the esketamine (n = 148) and control (n = 150) groups. Those in the esketamine group received a single intravenous injection of 0.25 mg/kg of esketamine immediately after fetal delivery, followed by 50 mg of esketamine as an adjuvant in patient-controlled intravenous analgesia for 48 hours after surgery. Saline was given to the control group of patients. Main Outcomes and Measures: The primary outcome was assessments of PPD symptoms by using the Edinburgh Postnatal Depression Scale (EPDS) at postpartum day 7. Positive screening for PPD was defined as a score of 10 or more points on the EPDS. In addition, the EPDS was analyzed as a continuous variable to evaluate depressive symptoms. Secondary outcomes included the Numeric Rating Scale (NRS) of postoperative pain, along with safety evaluations including adverse events and clinical assessments at postpartum days 14, 28, and 42. Results: A total of 298 pregnant women were included, with 150 in the control group (median age, 31.0 years [IQR, 29.0-34.0 years]) and 148 in the esketamine group (median age, 31.0 years [IQR, 28.0-34.0 years]). The prevalence of depression symptoms was significantly lower among patients given esketamine compared with controls (23.0% [34 of 148] vs 35.3% [53 of 150]; odds ratio, 0.55; 95% CI, 0.33-0.91; P = .02) on postpartum day 7. In addition, the esketamine group also showed a significantly lower change in EPDS scores (difference of least-squares means [SE], -1.17 [0.44]; 95% CI, -2.04 to -0.31; effect size, 0.74; P = .008). However, there were no differences between the groups in the incidence of positive screening results for PPD or in changes from the baseline EPDS scores at postpartum days 14, 28, and 42. There were no differences in NRS scores at rest and on movement except on movement at 72 hours postoperatively, when scores were significantly lower in the esketamine group (median, 3.0 [IQR, 2.0-3.0] vs 3.0 [IQR, 3.0-3.5]; median difference, 0 [95% CI, 0-0]; P = .03). Conclusions and Relevance: These results suggest that intravenous administration of esketamine during the perioperative period of elective cesarean delivery can improve depression symptoms during the early postpartum period. However, this antidepression effect may not be universally applicable to patients with low EPDS scores. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100054199.

Immunoantitumor Activity and Oxygenation Effect Based on Iron-Copper-Doped Folic Acid Carbon Dots.

Cancer metastasis and recurrence are closely associated with immunosuppression and a hypoxic tumor microenvironment. Chemodynamic therapy (CDT) and photothermodynamic therapy (PTT) have been shown to induce immunogenic cell death (ICD), effectively inhibiting cancer metastasis and recurrence when combined with immune adjuvants. However, the limited efficacy of Fenton's reaction and suboptimal photothermal effect present significant challenges for successfully inducing ICD through CDT and PTT. This paper described the synthesis and immunoantitumor activity of the novel iron-copper-doped folic acid carbon dots (CFCFB). Copper-doped folic acid carbon dots (Cu-FACDs) were initially synthesized via a hydrothermal method, using folic acid and copper gluconate as precursors. Subsequently, the nanoparticles CFCFB were obtained through cross-linking and self-assembly of Cu-FACDs with ferrocene dicarboxylic acid (FeDA) and 3-bromopyruvic acid (3BP). The catalytic effect of carbon dots in CFCFB enhanced the activity of the Fenton reaction, thereby promoting CDT-induced ICD and increasing the intracellular oxygen concentration. Additionally, 3BP inhibited cellular respiration, further amplifying the oxygen concentration. The photothermal conversion efficiency of CFCFB reached 55.8%, which significantly enhanced its antitumor efficacy through photothermal therapy. Immunofluorescence assay revealed that treatment with CFCFB led to an increased expression of ICD markers, including calreticulin (CRT) and ATP, as well as extracellular release of HMGB-1, indicating the induction of ICD by CFCFB. Moreover, the observed downregulation of ARG1 expression indicates a transition in the tumor microenvironment from an immunosuppressive state to an antitumor state following treatment with CFCFB. The upregulation of IL-2 and CD8 expression facilitated the differentiation of effector T cells, resulting in an augmented population of CD8+ T cells, thereby indicating the activation of systemic immune response.

Exploring gene biomarkers and targeted drugs for ferroptosis and cuproptosis in osteosarcoma: A bioinformatic approach.

Osteosarcoma predominantly affects adolescents and young adults and is characterized as a malignant bone tumor. In recent decades, substantial advancements have been achieved in both diagnosing and treating osteosarcoma. Resulting in enhanced survival rates. Despite these advancements, the intricate relationship between ferroptosis and cuproptosis genes in osteosarcoma remains inadequately understood. Leveraging TARGET and GEO datasets, we conducted Cox regression analysis to select prognostic genes from a cohort of 71 candidates. Subsequently, a novel prognostic model was engineered using the LASSO algorithm. Kaplan-Meier analysis demonstrated that patients stratified as low risk had a substantially better prognosis compared with their high-risk counterparts. The model's validity was corroborated by the area under the receiver operating characteristic (ROC) curve. Additionally, we ascertained independent prognostic indicators, including clinical presentation, metastatic status, and risk scores, and crafted a clinical scoring system via nomograms. The tumor immune microenvironment was appraised through ESTIMATE, CIBERSORT, and single-sample gene set enrichment analysis. Gene expression within the model was authenticated through PCR validation. The prognostic model, refined by Cox regression and the LASSO algorithm, comprised two risk genes. Kaplan-Meier curves confirmed a significantly improved prognosis for the low-risk group in contrast to those identified as high-risk. For the training set, the ROC area under the curve (AUC) values stood at 0.636, 0.695, and 0.729 for the 1-, 3-, and 5-year checkpoints, respectively. Although validation set AUCs were 0.738, 0.668, and 0.596, respectively. Immune microenvironmental analysis indicated potential immune deficiencies in high-risk patients. Additionally, sensitivity to three small molecule drugs was investigated in the high-risk cohort, informing potential immunotherapeutic strategies for osteosarcoma. PCR analysis showed increased mRNA levels of the genes FDX1 and SQLE in osteosarcoma tissues. This study elucidates the interaction of ferroptosis and cuproptosis genes in osteosarcoma and paves the way for more targeted immunotherapy.

Biomagnification of persistent organic pollutants (POPs) in detritivorous, phytophagous, and predatory invertebrates: How POPs enter terrestrial food web?

Invertebrates are primary contributors to fluxes of nutrients, energy, and contaminants in terrestrial food webs, but the trophodynamic of contaminants in invertebrate food chains is not fully understood. In this study, occurrence and biomagnification of persistent organic pollutants (POPs) were assessed in detritivorous, phytophagous, and predatory invertebrate food chains. Detritivorous species (earthworm and dung beetle) have higher concentrations of POPs than other species. Different composition patterns and biomagnification factors (BMFs) of POPs were observed for invertebrate species. Negative correlations were found between BMFs and log KOW of POPs for detritivorous and most phytophagous species. In contrast, parabolic relationships between BMFs and log KOW were observed in snails and predatory species, possibly attributed to the efficient digestion and absorption of diet and POPs for them. Bioenergetic characteristics are indicative of the biomagnification potential of POPs in terrestrial wildlife, as suggested by the significant and positive correlation between basal metabolic rates (BMRs) and BMFs of BDE 153 for invertebrates, amphibians, reptiles, birds, and mammals. The estimations of dietary exposure suggest that the terrestrial predators, especially feeding on the underground invertebrates, could be exposed to high level POPs from invertebrates.

Sodium-alginate-based indicator film containing a hydrophobic nanosilica layer for monitoring fish freshness.

In this study, hydrophobic sodium alginate/anthocyanin/cellulose nanocrystal indicator films were fabricated by incorporating nanosilica (NS) as a waterproofing layer. The concentrations and formation methods (spraying (S), coating (C), and impregnation (I)) of the NS layer (denoted as NSS, NSC, NSI, respectively) were optimized. The results indicated that the optimum concentration of the NS layer was 5 % at a water contact angle (WCA) 110.5°. Further, Fourier transform infrared spectra showed the presence of SiOSi and SiCH3 groups in the NSS, NSC, and NSI films, and X-ray diffraction spectra indicated that original structures of these films were disordered. Moreover, the surface morphology, mechanical properties, and light transmission were affected by the NS layer, and the optimal layer was found to be NSI. After 10 days of storage at 100 % humidity, the NSI film exhibited low water vapor adsorption (37.22 g) and permeability (0.1484 g/m·s·Pa·10-11) and a high WCA (110.2°). In addition, the NSI film exhibited a visible color shift with an increasing pH of the buffer solution. A monitoring test of fish freshness showed that the NSI film displayed a distinctive color change corresponding to fish spoilage during 14 days of storage. This indicates that NSI has high potential in indicator film applications.

CD4 T cell-secreted IFN-γ in Sjögren's syndrome induces salivary gland epithelial cell ferroptosis.

BACKGROUND: Sjögren's syndrome (SS) is a chronic autoimmune disease that predominantly affects exocrine glands. Previous studies have demonstrated that upregulated interferon-gamma (IFN-γ) in SS triggers ferroptosis in salivary gland epithelial cells (SGECs), resulting in impaired salivary gland secretion. However, the immune cells responsible for secreting IFN-γ remain unclear. Therefore, this study conducted bioinformatics analysis and molecular validation to identify the origin of IFN-γ in SS salivary gland. METHODS: The 'limma' package in R software was utilized to identify differentially expressed genes (DEGs) in the human SS dataset. Subsequently, the identified DEGs were compared with the ferroptosis database and screened through Cytoscape to determine candidate genes. The cellular localization and expression patterns of candidate genes were further confirmed in the salivary gland single-cell RNA sequence (scRNA-seq) data set from healthy control and SS mice. Furthermore, in vitro and in vivo studies were performed to analyze the effect of CD4 T-secreted IFN-γ on SGECs' ferroptosis and functions. RESULTS: Upregulated TLR4, IFNG, and IL33 were screened as candidates ferroptosis ferroptosis-inducing genes in SS salivary glands. The association of IFNG and IL33 with CD4 T cells was established through immune infiltration analysis. The expression of IFN-γ on CD4 T cells was robustly higher compared with that of IL33 as evidenced by scRNA-seq and immunofluorescence co-localization. Subsequent experiments conducted on candidate genes consistently demonstrated the potent ability of IFN-γ to induce SGECs' ferroptosis and inhibit AQP5 expression. CONCLUSIONS: Our findings indicate that CD4 T cell-secreted IFN-γ in SS induces SGECs' ferroptosis and inhibits AQP5 expression.

Analysis of physical activity and prescription opioid use among US adults: a cross-sectional study.

BACKGROUND: Opioid crisis has become a global concern, but whether physical activity (PA) can effectively reduce prescription opioid use remains unclear. The study aimed to examine the relationship of different domains of PA (e.g., occupation-related PA [OPA], transportation-related PA [TPA], leisure-time PA [LTPA]) with prescription opioid use and duration of prescription opioid use. METHODS: This cross-sectional study was conducted on 27,943 participants aged ≥ 18 years from National Health and Nutrition Examination Survey (NHANES, 2007- March 2020). We examined the relationship of different domains of PA with prescription opioid use and duration of prescription opioid use using multivariable logistic regression. Stratified analysis and a series of sensitivity analysis were used to elevate robustness. All analyses were conducted using appropriate sampling weights. RESULTS: Of the 27,943 participants, the mean age was 45.10 years, with 14,018 [weighted, 50.0%] females and 11,045 [weighted, 66.0%] non-Hispanic White. After multivariable adjustment, inverse associations between PA and prescription opioid use were observed for sufficient (≥ 150 min/week) total PA (OR,0.68 95%CI [0.56-0.81]), TPA (OR,0.73 95%CI [0.58-0.92]), and LTPA (OR,0.60 95%CI [0.48-0.75]) compared with insufficient PA(< 150 min/week), but not for sufficient OPA (OR,0.93 95%CI [0.79-1.10]). In addition, the associations were dose-responsive, participants had 22-40%, 27-36%, and 26-47% lower odds of using prescription opioids depending on the duration of total PA, TPA, and LTPA, respectively. Nevertheless, the impact of PA on prescription opioid use varied by duration of opioid use. Sufficient total PA was associated with elevated odds of short-term use of prescription opioids (< 90 days). Comparatively, sufficient total PA, TPA, and LTPA had different beneficial effects on reducing long-term use of prescription opioids (≥ 90 days) depending on the strength of opioids. CONCLUSIONS: This study demonstrated sufficient total PA, TPA, and LTPA were inversely associated with prescription opioid use and varied depending on the duration and strength of prescription opioid use. These findings highlight PA can provide policy guidance to address opioid crisis.

pH-Responsive Hyaluronic Acid Nanomicelles for Photodynamic /Chemodynamic Synergistic Therapy Trigger Immunogenicity and Oxygenation.

Cancer metastasis and invasion are closely related to tumor cell immunosuppression and intracellular hypoxia. Activation of immunogenicity and intracellular oxygenation are effective strategies for cancer treatment. In this study, multifunctional nanomicelle hyaluronic acid and cinnamaldehyde is self-assembled into nanomicelles (HPCNPs) were constructed for immunotherapy and tumor cell oxygenation. The Schiff base was constructed of HPCNPs with pyropheophorbide a-Cu (PPa-Cu). HPCNPs are concentrated in tumor sites under the guidance of CD44 proteins, and under the stimulation of tumor environment (weakly acidic), the Schiff base is destroyed to release free PPa. HPCNPs with photodynamic therapeutic functions and chemokinetic therapeutic functions produce a large number of reactive oxygen species (1O2 and •OH) under exogenous (laser) and endogenous (H2O2) stimulations, causing cell damage, and then inducing immunogenic cell death (ICD). ICD markers (CRT and ATP) and immunoactivity markers (IL-2 and CD8) were characterized by immunofluorescence. Downregulation of Arg1 protein proved that the tumor microenvironment changed from immunosuppressive type (M2) to antitumor type (M1). The oxidation of glutathione by HPCNP cascades to amplify the concentration of reactive oxygen species. In situ oxygenation by HPCNPs based on a Fenton-like reaction improves the intracellular oxygen level. In vitro and in vivo experiments demonstrated that HPCNPs combined with an immune checkpoint blocker (α-PD-L1) effectively ablated primary tumors, effectively inhibited the growth of distal tumors, and increased the oxygen level in tumor cells.

Elimination of copper obstacle factor in anaerobic digestion effluent for value-added utilization: Performance and resistance mechanisms of indigenous bacterial consortium.

The presence of excessive residual Cu(II), a high-risk heavy metal with potential toxicity and biomagnification property, substantially impede the value-added utilization of anaerobic digestion effluent (ADE). This study adapted indigenous bacterial consortium (IBCs) to eliminate Cu(II) from ADE, and their performances and resistance mechanisms against Cu(II) were analyzed. Results demonstrated that when the Cu(II) exposure concentration exceeded 7.5 mg/L, the biomass of IBCs decreased significantly, cells produced a substantial amount of ROS and EPS, at which time the intracellular Cu(II) content gradually decreased, while Cu(II) accumulation within the EPS substantially increased. The combined features of a high PN/PS ratio, a reversed Zeta potential gradient, and abundant functional groups within EPS collectively render EPS a primary diffusion barrier against Cu(II) toxicity. Mutual physiological and metagenomics analyses reveal that EPS synthesis and secretion, efflux, DNA repair along with coordination between each other were the primary resistance mechanisms of IBCs against Cu(II) toxicity. Furthermore, IBCs exhibited enhanced resistance by enriching bacteria carrying relevant resistance genes. Continuous pretreatment of actual ADE with IBCs at a 10-day hydraulic retention time (HRT) efficiently eliminated Cu(II) concentration from 5.01 mg/L to ∼0.68 mg/L by day 2. This elimination remained stable for the following 8 days of operation, further validated their good Cu(II) elimination stability. Notably, supplementing IBCs with 200 mg/L polymerized ferrous sulfate significantly enhanced their settling performance. By elucidating the intricate interplay of Cu(II) toxicity and IBC resistance mechanisms, this study provides a theoretical foundation for eliminating heavy metal barriers in ADE treatment.

Effect of clove essential oil nanoemulsion on physicochemical and antioxidant properties of chitosan film.

This study evaluated the physicochemical and antioxidant properties of clove essential oil (0, 0.2, 0.4, 0.6, 0.8, 1.0 % v/v) nanoemulsion (CEON) loaded chitosan-based films. With the increasing concentrations of the CEON, the thickness, b* and ΔE values of the films increased significantly (P < 0.05), while L* and light transmission dropped noticeably (P < 0.05). The hydrogen bonds formed between the CEON and chitosan could be demonstrated through Fourier-transform infrared spectra, indicating their good compatibility and intermolecular interactions. Furthermore, the added CEON considerably reduced the crystallinity and resulted in a porous structure of the films, as observed through X-ray diffraction plots and scanning electron microscopy images, respectively. This eventually led to a drop in both tensile strength and moisture content of the films. Moreover, the antioxidant properties were significantly enhanced (P < 0.05) with the increase in the amount of clove essential oil (CEO) due to the encapsulation of CEO by the nanoemulsion. Films containing 0.6 % CEO had higher elongation at break, higher water contact angle, lower water solubility, lower water vapor permeability, and lower oxygen permeability than the other films; therefore, such films are promising for application in meat preservation.