Identifying suitable candidates for pancreaticoduodenectomy with extended lymphadenectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: To evaluate long-term quality of life and survival in pancreatic ductal adenocarcinoma (PDAC) patients after pancreatoduodenectomy with extended lymphadenectomy (PDEL) and identify candidates. METHODS: Patients with resectable PDAC with ≥1 examined lymph node (LN) during pancreatoduodenectomy (PD), and were divided into the PD with standard lymphadenectomy (PDSL) and PDEL groups. Perioperative data, long-term quality of life and survival were compared, and the prognostic effect of LNs ± in every peripancreatic station were analysed. RESULTS: Screening 446 PDAC patients, 237 and 126 were included in the PDSL and PDEL groups, respectively. The PDEL group showed a longer operation time, greater intraoperative blood loss, severe diarrhoea, a higher incidence of grade III complications. Notably, the PDEL patients experienced significant relief from low back pain and diarrhoea, with an obvious survival advantage (p = 0.037), especially in patients with preoperative tumor contact with vascular and pathological N0; however, LNs+ in any station (No. 8p, 12, 14, or 16) were associated with a poorer prognosis. The vascular reconstruction, T and N stage were independent risk factors for survival. CONCLUSION: PDEL can relieve symptoms and prolong the survival of PDAC patients with acceptable complications, and EL should be performed regardless of preoperative LN enlargement.

The lncRNA LINC01605 promotes the progression of pancreatic ductal adenocarcinoma by activating the mTOR signaling pathway.

BACKGROUND: This study investigated the molecular mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in the process of tumor growth and liver metastasis of pancreatic ductal adenocarcinoma (PDAC). METHODS: LINC01605 was filtered out with specificity through TCGA datasets (related to DFS) and our RNA-sequencing data of PDAC tissue samples from Renji Hospital. The expression level and clinical relevance of LINC01605 were then verified in clinical cohorts and samples by immunohistochemical staining assay and survival analysis. Loss- and gain-of-function experiments were performed to estimate the regulatory effects of LINC01605 in vitro. RNA-seq of LINC01605-knockdown PDAC cells and subsequent inhibitor-based cellular function, western blotting, immunofluorescence and rescue experiments were conducted to explore the mechanisms by which LINC01605 regulates the behaviors of PDAC tumor cells. Subcutaneous xenograft models and intrasplenic liver metastasis models were employed to study its role in PDAC tumor growth and liver metastasis in vivo. RESULTS: LINC01605 expression is upregulated in both PDAC primary tumor and liver metastasis tissues and correlates with poor clinical prognosis. Loss and gain of function experiments in cells demonstrated that LINC01605 promotes the proliferation and migration of PDAC cells in vitro. In subsequent verification experiments, we found that LINC01605 contributes to PDAC progression through cholesterol metabolism regulation in a LIN28B-interacting manner by activating the mTOR signaling pathway. Furthermore, the animal models showed that LINC01605 facilitates the proliferation and metastatic invasion of PDAC cells in vivo. CONCLUSIONS: Our results indicate that the upregulated lncRNA LINC01605 promotes PDAC tumor cell proliferation and migration by regulating cholesterol metabolism via activation of the mTOR signaling pathway in a LIN28B-interacting manner. These findings provide new insight into the role of LINC01605 in PDAC tumor growth and liver metastasis as well as its value for clinical approaches as a metabolic therapeutic target in PDAC.

Bridging cultures: Chinese elements in scientific illustrations.

In the context of globalization, the integration of cultural elements into scientific research, particularly through the incorporation of traditional Chinese cultural motifs in scientific illustrations, represents a novel frontier in enhancing the universality and appeal of scientific discoveries. This paper explores the innovative practice of embedding traditional Chinese cultural elements into scientific paper illustrations, highlighting its significant role in augmenting the global appeal of research findings, promoting diversity and innovation in scientific inquiry, and facilitating cross-cultural understanding. Through a series of case studies, including symbolic representations of ancient myths and the use of traditional themes to elucidate complex scientific phenomena, we demonstrate how this cultural integration not only makes scientific content more accessible and engaging but also fosters a deeper appreciation of Chinese heritage among international audiences. This approach not only bridges the gap between science and culture but also contributes to a more inclusive and interconnected global scientific community, underscoring the importance of cultural diversity in enriching scientific exploration and communication.

Nanoporous copper titanium tin (np-Cu2TiSn) Heusler alloy prepared by dealloying-induced phase transformation for electrocatalytic nitrate reduction to ammonia.

Heusler alloys are a series of well-established intermetallic compounds with abundant structure and elemental substitutions, which are considered as potentially valuable catalysts for integrating multiple reactions owing to the features of ordered atomic arrangement and optimized electronic structure. Herein, a nanoporous copper titanium tin (np-Cu2TiSn) Heusler alloy is successfully prepared by the (electro)chemical dealloying transformation method, which exhibits high nitrate (NO3-) reduction performance with an NH3 Faradaic efficiency of 77.14 %, an NH3 yield rate of 11.90 mg h-1 mg-1cat, and a stability for 100 h under neutral condition. Significantly, we also convert NO3- to high-purity ammonium phosphomolybdate with NH4+ collection efficiency of 83.8 %, which suggests a practical approach to convert wastewater nitrate into value-added ammonia products. Experiments and theoretical calculations reveal that the electronic structure of Cu sites is modulated by the ligand effect of surrounding Ti and Sn atoms, which can simultaneously enhance the activation of NO3-, facilitate the desorption of NH3, and reduce the energy barriers, thereby boosting the electrochemical nitrate reduction reaction.

Transition of cooking fuels and obesity risk in Chinese adults.

BACKGROUND: Since 1990 s, China has witnessed a widespread transition to clean cooking fuels, presenting an opportunity to investigate whether household fuel transition could mitigate obesity risk and reconcile inconsistencies in the literature regarding the association between cooking fuels and obesity. METHODS: The China Health and Nutrition Survey (CHNS) is a prospective cohort study covering 12 provinces of China (1989-2015). Participants were classified into persistent cleaner fuel users, fuel transitioners, and persistent polluting fuel users according to self-reported primary cooking fuels. Obesity and central obesity were defined as BMI ≥ 28.0 kg/m2 and waist circumference ≥ 90 cm in men and ≥ 85 cm in women according to Chinese criteria. FINDINGS: Among 13,032 participants, 3657 (28.06 %) were persistent cleaner fuel users; 5264 (40.39 %) transitioned from using polluting fuels to cleaner fuels after the baseline survey; and 4111 (31.55 %) were persistent polluting fuel users. During the period of follow-up of 9.0 ± 6.8 years, 1248 (9.58 %) participants were classified into the obesity category, and 4703 (36.09 %) into the central obesity category. Persistent polluting fuel users had a significantly higher risk of developing obesity (hazard ratio [HR]: 1.45, 95 %CI: 1.22-1.72) and central obesity (HR: 1.32, 95 %CI: 1.21-1.44), compared to persistent cleaner fuel users. Persistent polluting fuel use was positively associated with developing obesity in women (HR: 1.64, 95 %CI: 1.30-2.06), but not in men. Subgroup analyses showed higher HR of persistent polluting fuel use among individuals aged 18-44 years (HR: 2.04, 95 %CI: 1.62-2.56). In contrast, the transitioners did not exhibit a significantly different risk of developing obesity (HR: 0.94, 95 %CI: 0.80-1.10) compared to persistent cleaner fuel users, which was consistent across different sex, age and urbanicity. Similar trends were observed for developing central obesity. INTERPRETATION: Persistent polluting fuel use increased obesity risk while the obesity risk of the transition to cleaner fuels was similar to persistent use of cleaner fuels. The finding underscores the significance of advocating for the adoption of cleaner fuels as a strategy to mitigate the disease burden associated with obesity.

Magnetic-guided nanocarriers for ionizing/non-ionizing radiation synergistic treatment against triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with the worst prognosis. Radiotherapy (RT) is one of the core modalities for the disease; however, the ionizing radiation of RT has severe side effects. The consistent development direction of RT is to achieve better therapeutic effect with lower radiation dose. Studies have demonstrated that synergistic effects can be achieved by combining RT with non-ionizing radiation therapies such as light and magnetic therapy, thereby achieving the goal of dose reduction and efficacy enhancement. METHODS: In this study, we applied FeCo NPs with magneto thermal function and phototherapeutic agent IR-780 to construct an ionizing and non-ionizing radiation synergistic nanoparticle (INS NPs). INS NPs are first subjected to morphology, size, colloidal stability, loading capacity, and photothermal conversion tests. Subsequently, the cell inhibitory and cellular internalization were evaluated using cell lines in vitro. Following comprehensive assessment of the NPs' in vivo biocompatibility, tumor-bearing mouse model was established to evaluate their distribution, targeted delivery, and anti-tumor effects in vivo. RESULTS: INS NPs have a saturation magnetization exceeding 72 emu/g, a hydrodynamic particle size of approximately 40 nm, a negatively charged surface, and good colloidal stability and encapsulation properties. INS NPs maintain the spectral characteristics of IR-780 at 808 nm. Under laser irradiation, the maximum temperature was 92 °C, INS NPs also achieved the effective heat temperature in vivo. Both in vivo and in vitro tests have proven that INS NPs have good biocompatibility. INS NPs remained effective for more than a week after one injection in vivo, and can also be guided and accumulated in tumors through permanent magnets. Later, the results exhibited that under low-dose RT and laser irradiation, the combined intervention group showed significant synergetic effects, and the ROS production rate was much higher than that of the RT and phototherapy-treated groups. In the mice model, 60% of the tumors were completely eradicated. CONCLUSIONS: INS NPs effectively overcome many shortcomings of RT for TNBC and provide experimental basis for the development of novel clinical treatment methods for TNBC.

Single-cell transcriptome sequencing reveals SPP1-CD44-mediated macrophage-tumor cell interactions drive chemoresistance in TNBC.

Triple-negative breast cancer (TNBC) is often considered one of the most aggressive subtypes of breast cancer, characterized by a high recurrence rate and low overall survival (OS). It is notorious for posing challenges related to drug resistance. While there has been progress in TNBC research, the mechanisms underlying chemotherapy resistance in TNBC remain largely elusive. We collect single-cell RNA sequencing (scRNA-seq) data from five TNBC patients susceptible to chemotherapy and five resistant cases. Comprehensive analyses involving copy number variation (CNV), pseudotime trajectory, cell-cell interactions, pseudospace analysis, as well as transcription factor and functional enrichment are conducted specifically on macrophages and malignant cells. Furthermore, we performed validation experiments on clinical samples using multiplex immunofluorescence. We identified a subset of SPP1+ macrophages that secrete SPP1 signals interacting with CD44 on malignant cell surfaces, potentially activating the PDE3B pathway within malignant cells via the integrin pathway, leading to chemotherapy resistance. The abnormally enhanced SPP1 signal between macrophages and malignant cells may serve as a factor promoting chemotherapy resistance in TNBC patients. Therefore, SPP1+ macrophages could potentially serve as a therapeutic target to reduce chemotherapy resistance.

Deoxycholic acid inducing chronic atrophic gastritis with colonic mucosal lesion correlated to mucosal immune dysfunction in rats.

The present study aimed to explore the underlying mechanism of bile reflux-inducing chronic atrophic gastritis (CAG) with colonic mucosal lesion. The rat model of CAG with colonic mucosal lesion was induced by free-drinking 20 mmol/L sodium deoxycholate to simulate bile reflux and 2% cold sodium salicylate for 12 weeks. In comparison to the control group, the model rats had increased abundances of Bacteroidetes and Firmicutes but had decreased abundances of Proteobacteria and Fusobacterium. Several gut bacteria with bile acids transformation ability were enriched in the model group, such as Blautia, Phascolarctobacter, and Enterococcus. The cytotoxic deoxycholic acid and lithocholic acid were significantly increased in the model group. Transcriptome analysis of colonic tissues presented that the down-regulated genes enriched in T cell receptor signaling pathway, antigen processing and presentation, Th17 cell differentiation, Th1 and Th2 cell differentiation, and intestinal immune network for IgA production in the model group. These results suggest that bile reflux-inducing CAG with colonic mucosal lesion accompanied by gut dysbacteriosis, mucosal immunocompromise, and increased gene expressions related to repair of intestinal mucosal injury.

Engineering an energy-dissipating hybrid tissue in vivo for obesity treatment.

Obesity is a global health challenge with limited therapeutic solutions. Here, we demonstrate the engineering of an energy-dissipating hybrid tissue (EDHT) in the body for weight control. EDHT is constructed by implanting a synthetic gel matrix comprising immunomodulatory signals and functional cells into the recipient mouse. The immunomodulatory signals induce the host stromal cells to create an immunosuppressive niche that protects the functional cells, which are overexpressing the uncoupling protein 1 (UCP1), from immune rejection. Consequently, these endogenous and exogenous cells co-develop a hybrid tissue that sustainedly produces UCP1 to accelerate the host's energy expenditure. Systematic experiments in high-fat diet (HFD) and transgenic (ob/ob) mice show that EDHT efficiently reduces body weight and relieves obesity-associated pathological conditions. Importantly, an 18-month observation for safety assessment excludes cell leakage from EDHT and reports no adverse physiological responses. Overall, EDHT demonstrates convincing efficacy and safety in controlling body weight.

Targeting Rab7-Rilp Mediated Microlipophagy Alleviates Lipid Toxicity in Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DbCM) is characterized by diastolic dysfunction, which progresses into heart failure and aberrant electrophysiology in diabetic patients. Dyslipidemia in type 2 diabetic patients leads to the accumulation of lipid droplets (LDs) in cardiomyocytes and results in lipid toxicity which has been suggested to drive DbCM. It is aimed to explore potential pathways that may boost LDs degradation in DbCM and restore cardiac function. LDs accumulation resulted in an increase in lipid toxicity in DbCM hearts is confirmed. Microlipophagy pathway, rather than traditional macrolipophagy, is activated in DbCM hearts. RNA-Seq data and Rab7-CKO mice implicate that Rab7 is a major modulator of the microlipophagy pathway. Mechanistically, Rab7 is phosphorylated at Tyrosine 183, which allows the recruitment of Rab-interacting lysosome protein (Rilp) to proceed LDs degradation by lysosome. Treating DbCM mice with Rab7 activator ML-098 enhanced Rilp level and rescued the observed cardiac dysfunction. Overall, Rab7-Rilp-mediated microlipophagy may be a promising target in the treatment of lipid toxicity in DbCM is suggested.

Systemic oxidative stress levels during the course of pregnancy: Associations with exposure to air pollutants.

Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM2.5), and nitrogen dioxide (NO2). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM2.5, NO2, and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM2.5 concentration (3.20 µg/m3) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2nd (-7.99%, 95% CI: 13.8%, -2.23%) or 3rd trimester (-2.81%, 95% CI: 10.0%, 4.38%). The average cumulative PM2.5 exposures in the 3-7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM2.5 concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO2 exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM2.5 and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure.

Effects of ambient temperature on pediatric incident seizure: A case-crossover analysis using distributed lag non-linear models.

OBJECTIVE: Emerging evidence supports that brain dysfunction may be attributable to environmental factors. This study aims to examine associations of ambient temperature and temperature variability (TV) with seizure incidence in children, which has not been explored. MATERIAL AND METHODS: Data on 2718 outpatient visits due to seizure were collected in Shanghai, China, from 2018 to 2023. Exposure to ambient temperature was estimated at children's residential addresses using spatial-temporal models. A time-stratified case-crossover design with a distributed lag non-linear model (DLNM) was conducted to assess the association between seizure incidence and daily average of ambient temperature over a period of 21 days prior to a case date of disease onset. For a given case date, we selected all dates falling on the same day of the week within the same month as control dates. We calculated a composite index of intra-day and inter-day TV, which was the standard deviation of the daily minimum and maximum temperatures, respectively, over 7 days preceding a case date. We then assessed the association between TV and seizure incidence. Stratified analyses were conducted by age (73.51% < 5 years old and 26.49 % ≥ 5 years old), sex (41.83% female), presence of fever (69.72%), and diagnosis of epilepsy (27.63%). RESULTS: We observed inversed J-shaped temperature-response curves. Lower temperatures had a significant and prolonged effect than higher temperatures. Using 20 °C (with the minimum effect) as the reference, the cumulative odds ratios (ORs) for over 0-21 days preceding the onset at the 5th percentile of the temperature (3 °C) and at the 95th percentile (29 °C) were 3.17 (95% CI: 1.77, 5.68) and 1.54 (95% CI: 0.97, 2.44), respectively. In addition, per 1 °C increases in TV0-7 was associated with OR of 1.08 (95% CI: 1.01, 1.15). Older children and those experiencing seizure with fever exhibited a higher risk of seizure onset at both lower and higher ambient temperatures. CONCLUSION: Both low and high temperatures can contribute to the morbidity related to pediatric seizure. Lower temperatures, however, exerted a longer period of effect prior to seizure onset than higher temperatures. An increased risk for incident seizure was significantly associated with temperature variability during preceding 7 days.

Mechanically skin-like and water-resistant self-healing bioelastomer for high-tension wound healing.

The biomedical application of self-healing materials in wet or (under)water environments is quite challenging because the insulation and dissociation effects of water molecules significantly reduce the reconstruction of material-interface interactions. Rapid closure with uniform tension of high-tension wounds is often difficult, leading to further deterioration and scarring. Herein, a new type of thermosetting water-resistant self-healing bioelastomer (WRSHE) was designed by synergistically incorporating a stable polyglycerol sebacate (PGS) covalent crosslinking network and triple hybrid dynamic networks consisting of reversible disulfide metathesis (SS), and dimethylglyoxime urethane (Dou) and hydrogen bonds. And a resveratrol-loaded WRSHE (Res@WRSHE) was developed by a swelling, absorption, and crosslinked network locking strategy. WRSHEs exhibited skin-like mechanical properties in terms of nonlinear modulus behavior, biomimetic softness, high stretchability, and good elasticity, and they also achieved ultrafast and highly efficient self-healing in various liquid environments. For wound-healing applications of high-tension full-thickness skin defects, the convenient surface assembly by self-healing of WRSHEs provides uniform contraction stress to facilitate tight closure. Moreover, Res@WRSHEs gradually release resveratrol, which helps inflammatory response reduction, promotes blood vessel regeneration, and accelerates wound repair.

Angiopoietin-like protein 2 inhibits thrombus formation.

Acute myocardial infarction is mainly caused by a lack of blood flood in the coronary artery. Angiopoietin-like protein 2 (ANGPTL2) induces platelet activation and thrombus formation in vitro through binding with immunoglobulin-like receptor B, an immunoglobulin superfamily receptor. However, the mechanism by which it regulates platelet function in vivo remains unclear. In this study, we investigated the role of ANGPTL2 during thrombosis in relationship with ST-segment elevation myocardial infarction (STEMI) with spontaneous recanalization (SR). In a cohort of 276 male and female patients, we measured plasma ANGPTL2 protein levels. Using male Angptl2-knockout and wild-type mice, we examined the inhibitory effect of Angptl2 on thrombosis and platelet activation both in vivo and ex vivo. We found that plasma and platelet ANGPTL2 levels were elevated in patients with STEMI with SR compared to those in non-SR (NSR) patients, and was an independent predictor of SR. Angptl2 deficiency accelerated mesenteric artery thrombosis induced by FeCl3 in Angptl2-/- compared to WT animals, promoted platelet granule secretion and aggregation induced by thrombin and collogen while purified ANGPTL2 protein supplementation reversed collagen-induced platelet aggregation. Angptl2 deficiency also increased platelet spreading on immobilized fibrinogen and clot contraction. In collagen-stimulated Angptl2-/- platelets, Src homology region 2 domain-containing phosphatase (Shp)1-Y564 and Shp2-Y580 phosphorylation were attenuated while Src, Syk, and Phospholipase Cγ2 (PLCγ2) phosphorylation increased. Our results demonstrate that ANGPTL2 negatively regulated thrombus formation by activating ITIM which can suppress ITAM signaling pathway. This new knowledge provides a new perspective for designing future antiplatelet aggregation therapies.

Reduced human fecundity attributable to ambient fine particles in low- and middle-income countries.

BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) has been associated with reduced human fecundity. However, the attributable burden has not been estimated for low- and middle-income countries (LMICs), where the exposure-response function between PM2.5 and the infertility rate has been insufficiently studied. OBJECTIVE: This study examined the associations between long-term exposure to PM2.5 and human fecundity indicators, namely the expected time to pregnancy (TTP) and 12-month infertility rate (IR), and then estimated PM2.5-attributable burden of infertility in LMICs. METHODS: We analyzed 164,593 eligible women from 100 Demographic and Health Surveys conducted in 49 LMICs between 1999 and 2021. We assessed PM2.5 exposures during the 12 months before a pregnancy attempt using the global satellite-derived PM2.5 estimates produced by Atmospheric Composition Analysis Group (ACAG). First, we created a series of pseudo-populations with balanced covariates, given different levels of PM2.5 exposure, using a matching approach based on the generalized propensity score. For each pseudo-population, we used 2-stage generalized Gamma models to derive TTP or IR from the probability distribution of the questionnaire-based duration time for the pregnancy attempt before the interview. Second, we used spline regressions to generate nonlinear PM2.5 exposure-response functions for each of the two fecundity indicators. Finally, we applied the exposure-response functions to estimate number of infertile couples attributable to PM2.5 exposure in 118 LMICs. RESULTS: Based on the Gamma models, each 10 µg/m3 increment in PM2.5 exposure was associated with a TTP increase by 1.7 % (95 % confidence interval [CI]: -2.3 %-6.0 %) and an IR increase by 2.3 % (95 %CI: 0.6 %-3.9 %). The nonlinear exposure-response function suggested a robust effect of an increased IR for high-concentration PM2.5 exposure (>75 µg/m3). Based on the PM2.5-IR function, across the 118 LMICs, the number of infertile couples attributable to PM2.5 exposure exceeding 35 µg/m3 (the first-stage interim target recommended by the World Health Organization global air quality guidelines) was 0.66 million (95 %CI: 0.061-1.43), accounting for 2.25 % (95 %CI: 0.20 %-4.84 %) of all couples affected by infertility. Among the 0.66 million, 66.5 % were within the top 10 % high-exposure infertile couples, mainly from South Asia, East Asia, and West Africa. CONCLUSION: PM2.5 contributes significantly to human infertility in places with high levels of air pollution. PM2.5-pollution control is imperative to protect human fecundity in LMICs.

Mechanism insights into the histopathological changes of polypropylene microplastics induced gut and liver in zebrafish.

Microplastics (MPs), emerging as significant pollutants, have been consistently detected in aquatic environments, with the Yangtze River experiencing a particularly severe level of microplastic pollution, exceeding all other watersheds in China. Polypropylene (PP), the plastic most abundantly found in the middle and lower reaches of the Yangtze River Basin, has less comprehensive research results into its toxic effects. Consequently, the present investigation employed zebrafish as a model organism to delve into the toxicological impacts of polypropylene microplastics (PP-MPs) with a diameter of 5 µm across varying concentrations (300 mg/L and 600 mg/L). Using histopathological, microbiota profiling, and transcriptomic approaches, we systematically evaluated the impact of PP-MPs exposure on the intestine and liver of zebrafish. Histopathological analysis revealed that exposure to PP-MPs resulted in thinner intestinal walls, damaged intestinal mucosa, and hepatic cellular damage. Intestinal microbiota profiling demonstrated that, the richness, uniformity, diversity, and homogeneity of gut microbes significantly increased after the PP-MPs exposure at high concentration. These alterations were accompanied by shifts in the relative abundance of microbiota associated with intestinal pathologies, suggesting a profound impact on the intestinal microbial community structure. Concurrently, hepatic transcriptome analysis and RT-qPCR indicated that the downregulation of pathways and genes associated with cell proliferation regulation and DNA damage repair mechanisms contributed to hepatic cellular damage, ultimately exerting adverse effects on the liver. Correlation analysis between the intestinal microbiota and liver transcriptome profiles further highlighted significant associations between intestinal microbiota and the downregulated hepatic pathways. Collectively, these results provide novel insights into the subacute toxicological mechanisms of PP-MPs in aquatic organisms and highlight the need for further research on the ecological and health risks associated with PP-MPs pollution.

Nanomaterials-assisted gene editing and synthetic biology for optimizing the treatment of pulmonary diseases.

The use of nanomaterials in gene editing and synthetic biology has emerged as a pivotal strategy in the pursuit of refined treatment methodologies for pulmonary disorders. This review discusses the utilization of nanomaterial-assisted gene editing tools and synthetic biology techniques to promote the development of more precise and efficient treatments for pulmonary diseases. First, we briefly outline the characterization of the respiratory system and succinctly describe the principal applications of diverse nanomaterials in lung ailment treatment. Second, we elaborate on gene-editing tools, their configurations, and assorted delivery methods, while delving into the present state of nanomaterial-facilitated gene-editing interventions for a spectrum of pulmonary diseases. Subsequently, we briefly expound on synthetic biology and its deployment in biomedicine, focusing on research advances in the diagnosis and treatment of pulmonary conditions against the backdrop of the coronavirus disease 2019 pandemic. Finally, we summarize the extant lacunae in current research and delineate prospects for advancement in this domain. This holistic approach augments the development of pioneering solutions in lung disease treatment, thereby endowing patients with more efficacious and personalized therapeutic alternatives.

Arachidonic Acid Metabolites in Self-collected Biospecimens Following Campfire Exposure: Exploring Non-invasive Biomarkers of Wildfire Health Effects.

Climate change has contributed to increased frequency and intensity of wildfire. Studying its acute effects is limited due to unpredictable nature of wildfire occurrence, which necessitates readily deployable techniques to collect biospecimens. To identify biomarkers of wildfire's acute effects, we conducted this exploratory study in eight healthy campers (four men and four women) who self-collected nasal fluid, urine, saliva, and skin wipes at different time points before, during, and after 4-hour exposure to wood smoke in a camping event. Concentrations of black carbon in the air and polycyclic aromatic hydrocarbons in participants' silicone wristbands were significantly elevated during the exposure session. Among 30 arachidonic acid metabolites measured, lipoxygenase metabolites were more abundant in nasal fluid and saliva, whereas cyclooxygenase and non-enzymatic metabolites were more abundant in urine. We observed drastic increases, at 8 hours following the exposure, in urinary levels of PGE2 (398%) and 15-keto-PGF2α (191%) (FDR<10%), with greater increases in men (FDR < 0.01%) than in women. No significant changes were observed for other metabolites in urine or the other biospecimens. Our results suggest urinary PGE2 and 15-keto-PGF2α as promising biomarkers reflecting pathophysiologic (likely sex-dependent) changes induced by short-term exposure to wildfire.

Engineering Short Antimicrobial Peptides to Specifically Target Fusobacterium nucleatum in the Mixed Microbial Population.

Antimicrobial peptides (AMPs) are becoming next-generation alternative antibacterial agents because of the rapid increase in resistance in bacteria against existing antibiotics, which can also be attributed to the formation of resilient biofilms. However, their widespread use is limited because of their poor absorption, higher dosage requirements, and delayed onset of the bioactivity to elicit a desired response. Here we developed a short AMP that specifically targeted Fusobacterium nucleatum. We conjugated 23R to a statherin-derived peptide (SDP) through rational design; this conjugate binds to FomA, a major porin protein of F. nucleatum. The SDP-tagged 23R exhibited rapid and highly specific bactericidal efficacy against F. nucleatum. Further, IC50 values were in the nanomolar range, and they were 100-fold lower than those obtained with unconjugated 23R. In a human gut microbiota model, 0.1 nM SDP-23R achieved 99% clearance of F. nucleatum ATCC 25586 without markedly altering resident microbiota. Here we demonstrated that binding-peptide-coupled AMPs show increased killing efficacy and specificity for the target pathogen without affecting the resident microbiota.

Glycerophospholipid metabolism changes association with ozone exposure.

Exposure to ozone (O3) has been associated with cardiovascular outcomes in humans, yet the underlying mechanisms of the adverse effect remain poorly understood. We aimed to investigate the association between O3 exposure and glycerophospholipid metabolism in healthy young adults. We quantified plasma concentrations of phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) using a UPLC-MS/MS system. Time-weighted personal exposures were calculated to O3 and co-pollutants over 4 time windows, and we employed orthogonal partial least squares discriminant analysis to discern differences in lipids profiles between high and low O3 exposure. Linear mixed-effects models and mediation analysis were utilized to estimate the associations between O3 exposure, lipids, and cardiovascular physiology indicators. Forty-three healthy adults were included in this study, and the mean (SD) time-weighted personal exposures to O3 was 9.08 (4.06) ppb. With shorter exposure durations, O3 increases were associated with increasing PC and lysoPC levels; whereas at longer exposure times, the opposite relationship was shown. Furthermore, two specific lipids, namely lysoPC a C26:0 and lysoPC a C17:0, showed significantly positive mediating effects on associations of long-term O3 exposure with pulse wave velocity and systolic blood pressure, respectively. Alterations in specific lipids may underlie the cardiovascular effects of O3 exposure.