Synthesis and Evaluation of Novel meso-Tetraphenyltetrabenzoporphyrins for Photodynamic Therapy.

To discover effective photosensitizers for photodynamic therapy (PDT), a series of new meso-tetraphenyltetrabenzoporphyrin (m-Ph4TBP) derivatives were designed, prepared, and characterized. All m-Ph4TBPs own two characteristic absorption bands in the range of 450-500 and 600-700 nm and have the ability to generate singlet oxygen upon photoexcitation. Most of the m-Ph4TBPs demonstrated high photoactivity, among which compounds I4, I6, I12, and I13 induced apoptosis and also exhibited excellent photodynamic activities in vivo. Nonetheless, the liver organs of the I4 and I6-PDT groups showed clear calcifications, whereas the liver tissues of the other PDT groups showed no calcification. It was indicated that compared to phenolic m-Ph4TBPs, glycol m-Ph4TBPs exhibited superior biological safety in mice. According to comprehensive evaluations, m-Ph4TBP I12 displayed excellent photodynamic antitumor efficacy and biological safety and can be regarded as a promising antitumor drug candidate.

Development and validation of machine learning models to predict MDRO colonization or infection on ICU admission by using electronic health record data.

BACKGROUND: Multidrug-resistant organisms (MDRO) pose a significant threat to public health. Intensive Care Units (ICU), characterized by the extensive use of antimicrobial agents and a high prevalence of bacterial resistance, are hotspots for MDRO proliferation. Timely identification of patients at high risk for MDRO can aid in curbing transmission, enhancing patient outcomes, and maintaining the cleanliness of the ICU environment. This study focused on developing a machine learning (ML) model to identify patients at risk of MDRO during the initial phase of their ICU stay. METHODS: Utilizing patient data from the First Medical Center of the People's Liberation Army General Hospital (PLAGH-ICU) and the Medical Information Mart for Intensive Care (MIMIC-IV), the study analyzed variables within 24 h of ICU admission. Machine learning algorithms were applied to these datasets, emphasizing the early detection of MDRO colonization or infection. Model efficacy was evaluated by the area under the receiver operating characteristics curve (AUROC), alongside internal and external validation sets. RESULTS: The study evaluated 3,536 patients in PLAGH-ICU and 34,923 in MIMIC-IV, revealing MDRO prevalence of 11.96% and 8.81%, respectively. Significant differences in ICU and hospital stays, along with mortality rates, were observed between MDRO positive and negative patients. In the temporal validation, the PLAGH-ICU model achieved an AUROC of 0.786 [0.748, 0.825], while the MIMIC-IV model reached 0.744 [0.723, 0.766]. External validation demonstrated reduced model performance across different datasets. Key predictors included biochemical markers and the duration of pre-ICU hospital stay. CONCLUSIONS: The ML models developed in this study demonstrated their capability in early identification of MDRO risks in ICU patients. Continuous refinement and validation in varied clinical contexts remain essential for future applications.

Enhance PD/A biofilm formation via a novel biochar/tourmaline modified-biocarriers to treat low-strength contaminated surface water: Initial adhesion and high-substrate microenvironment.

In this work, a novel polyurethane carrier modified with biochar and tourmaline/zeolite powder at ratio of 1:1 and 1:2 was developed to promote the formation of biofilms and the synergy of overall bacterial activity for Partial Denitrification/Anammox to treat low-nitrogen contaminated surface water. Based on the batch experiment, the modified biocarrier, BTP2 (biochar: tourmaline = 2: 1), exhibited the highest total nitrogen removal efficiency (83.63%) under influent total nitrogen of 15 mg/L and COD/NO3- of 3. The dense biofilm was formed in inner side of biocarrier owing to the increased surface roughness and various functional groups suggested by scanning electron microscopy and Fourier-transform infrared analysis. The EPS content increased from 200.15 to 220.26 mg/g VSS in BTP2 system. Besides, the rapid NH4+ capture and organics release of the modified carrier fueled the growth of anammox and denitrification bacteria, with the activity of 2.13 ± 0.52 mg N/gVSS/h and 6.70 ± 0.52 mg N/gVSS/h (BTP2). High-throughput sequencing unraveled the increased abundances of Candidatus_Competibacter (0.82%), Thauera (0.60%) and Candidatus_Brocadia (0.55%) which was responsible for the synergy of incomplete reduction of NO3- to NO2- and NH4+ oxidation. Overall, this study provided a valid and simple-control guide for biofilm formation towards rapid enrichment and great collaboration of Anammox and denitrification bacteria.

Data-Driven and Machine Learning to Screen Metal-Organic Frameworks for the Efficient Separation of Methane.

With the rapid growth of the economy, people are increasingly reliant on energy sources. However, in recent years, the energy crisis has gradually intensified. As a clean energy source, methane has garnered widespread attention for its development and utilization. This study employed both large-scale computational screening and machine learning to investigate the adsorption and diffusion properties of thousands of metal-organic frameworks (MOFs) in six gas binary mixtures of CH4 (H2/CH4, N2/CH4, O2/CH4, CO2/CH4, H2S/CH4, He/CH4) for methane purification. Firstly, a univariate analysis was conducted to discuss the relationships between the performance indicators of adsorbents and their characteristic descriptors. Subsequently, four machine learning methods were utilized to predict the diffusivity/selectivity of gas, with the light gradient boosting machine (LGBM) algorithm emerging as the optimal one, yielding R2 values of 0.954 for the diffusivity and 0.931 for the selectivity. Furthermore, the LGBM algorithm was combined with the SHapley Additive exPlanation (SHAP) technique to quantitatively analyze the relative importance of each MOF descriptor, revealing that the pore limiting diameter (PLD) was the most critical structural descriptor affecting molecular diffusivity. Finally, for each system of CH4 mixture, three high-performance MOFs were identified, and the commonalities among high-performance MOFs were analyzed, leading to the proposals of three design principles involving changes only to the metal centers, organic linkers, or topological structures. Thus, this work reveals microscopic insights into the separation mechanisms of CH4 from different binary mixtures in MOFs.

Disruption of zebrafish sex differentiation by emerging contaminants hexafluoropropylene oxides at environmental concentrations via antagonizing androgen receptor pathways.

As alternatives of perfluorooctanoic acid (PFOA), hexafluoropropylene oxide dimeric acid (HFPO-DA) and trimeric acid (HFPO-TA) have been detected increasingly in environmental media and even humans. They have been shown to exhibit reproductive toxicity to model species, but their effects on human remain unclear due to the knowledge gap in their mode of action. Herein, (anti-)androgenic effects of the two HFPOs and PFOA were investigated and underlying toxicological mechanism was explored by combining zebrafish test, cell assay and molecular docking simulation. Exposure of juvenile zebrafish to the chemicals during sex differentiation promoted feminization, with HFPO-TA acting at an environmental concentration of 1 µg/L. The chemicals inhibited proliferation of human prostate cells and transcriptional activity of human and zebrafish androgen receptors (AR), with HFPO-TA displaying the strongest potency. Molecular docking revealed that the chemicals bind to AR in a conformation similar to a known AR antagonist. Combined in vivo, in vitro and in silico results demonstrated that the chemicals disrupted sex differentiation likely by antagonizing AR-mediated pathways, and provided more evidence that HFPO-TA is not a safe alternative to PFOA.

Insights into the antineoplastic activity and mechanisms of action of coumarin-coordinated 8-hydroxyquinoline ruthenium(II/III) compounds.

Ruthenium(II/III) coordination compounds have gained widespread attention as chemotherapy drugs, photosensitizers, and photodynamic therapy reagents. Herein, a family of 11 novel coumarin-coordinated 8-hydroxyquinoline ruthenium(II/III) compounds, i.e., [RuII2(µ2-Cl)2(QL1a)2(DMSO)4] (YNU-4a = Yulin Normal University-4a), [RuII2(µ2-Cl)2(QL1b)2(DMSO)4] (YNU-4b), [RuII2(µ2-Cl)2(QL1c)2(DMSO)4] (YNU-4c), [RuII2(µ2-Cl)2(QL1d)2(DMSO)4]⋅2CH3OH (YNU-4d), [RuII(QL1e)2(DMSO)2] (YNU-4e), [RuIII(QL1e)2(QL3a)] (YNU-4f), [RuIII(QL1e)2(QL3b)] (YNU-4g), [RuIII(QL1e)2(QL3c)] (YNU-4h), [RuIICl2(H-QL3a)2(DMSO)2] (YNU-4i), [RuIICl2(H-QL3b)2(DMSO)2] (YNU-4j), and [RuIICl2(H-QL3c)2(DMSO)2] (YNU-4k), featuring the coligands 5,7-diiodo-8-hydroxyquinoline (H-QL1a), 5,7-dichloro-8-quinolinol (H-QL1b), 5-chloro-7-iodo-8-hydroxyquinolin (H-QL1c), 5,7-dibromo-8-hydroxyquinoline (H-QL1d), and 5,7-dichloro-8-hydroxy-2-methylquinoline (H-QL1e) and the main ligands 6,7-dichloro-3-pyridin-2-yl-chromen-2-one (H-QL3a), 6-bromo-3-pyridin-2-yl-chromen-2-one (H-QL3b), and 6-chloro-3-pyridin-2-yl-chromen-2-one (H-QL3c), respectively. The structure of compounds YNU-4a-YNU-4k was fully confirmed by conducting various spectroscopic analyses. The anticancer activity of YNU-4a-YNU-4k was evaluated in cisplatin-resistant A549/DDP lung cancer cells (LC549) versus normal embryonic kidney (HEK293) cells. Notably, compound YNU-4f bearing QL1e and QL3a ligands showed a more pronounced antiproliferative effect against LC549 cells (IC50 = 1.75 ± 0.09 µM) with high intrinsic selectivity toward LC549 cancer cells than YNU-4a-YNU-4e, H-QL1a-H-QL1e, cisplatin (PDD), YNU-4g-YNU-4k, and H-QL3a-H-QL3c. Additionally, a colocalization assay analysis of YNU-4e and YNU-4f showed that these two ruthenium(II/III) compounds were subcellularly accumulated in the mitochondria and other regions of the cytoplasm, where they induce mitophagy, adenosine triphosphate (ATP) reduction, mitochondrial respiratory chain complex I/IV(RC1/RC4) inhibition, and mitochondrial dysfunction. Accordingly, compounds YNU-4a-YNU-4k can be regarded as mitophagy inductors for the eradication of cisplatin-resistant LC549 cancer cells.

Multiple effects of spicy flavors on neurological diseases through the intervention of TRPV1: a critical review.

The spicy properties of foods are contributed by various spicy flavor substances (SFs) such as capsaicin, piperine, and allicin. Beyond their distinctive sensory characteristics, SFs also influence health conditions and numerous studies have associated spicy flavors with disease treatment. In this review, we enumerate different types of SFs and describe their role in food processing, with a specific emphasis on critically examining their influence on human wellness. Particularly, detailed insights into the mechanisms through which SFs enhance physiological balance and alleviate neurological diseases are provided, and a systematic analysis of the significance of transient receptor potential vanilloid type-1 (TRPV1) in regulating metabolism and nervous system homeostasis is presented. Moreover, enhancing the accessibility and utilization of SFs can potentially amplify the physiological effects. This review aims to provide compelling evidence for the integration of food flavor and human health.

Enhanced biodegradation of benzo[a]pyrene with Trametes versicolor stimulated by citric acid.

Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants with carcinogenic, mutagenic and teratogenic effects. The white-rot fungi in the fungal group have significant degradation ability for high molecular weight organic pollutants. However, exogenous fungi are easily antagonized by indigenous microorganisms. Low molecular weight organic acids, a small molecular organic matter secreted by plants, can provide carbon sources for soil microorganisms. Combining organic acids with white rot fungi may improve the nutritional environment of fungi. In this study, immobilized Trametes versicolor was used to degrade benzo[a]pyrene in soil, and its effect on removing benzo[a]pyrene in soil mediated by different low molecular weight organic acids was investigated. The results showed that when the degradation was 35 days, the removal effect of the experimental group with citric acid was the best, reaching 43.7%. The degradation effect of Trametes versicolor on benzo[a]pyrene was further investigated in the liquid medium when citric acid was added, and the effects of citric acid on the biomass, extracellular protein concentration and laccase activity of Trametes versicolor were investigated by controlling different concentrations of citric acid. In general, citric acid can act as a carbon source for Trametes versicolor and promote its extracellular protein secretion and laccase activity, thereby accelerating the mineralization of benzo[a]pyrene by Trametes versicolor. Therefore, citric acid can be used as a biostimulant in the remediation of PAHs contaminated soil with Trametes versicolor.

Assessment of metabolomic variations among individuals returning to plain areas after exposure to high altitudes: a metabolomic analysis of human plasma samples with high-altitude de-acclimatization syndrome.

Background: High altitude de-acclimatization (HADA) is gradually becoming a public health concern as millions of individuals of different occupations migrate to high-altitude areas for work due to economic growth in plateau areas. HADA affects people who return to lower elevations after exposure to high altitudes. It causes significant physiological and functional changes that can negatively impact health and even endanger life. However, uncertainties persist about the detailed mechanisms underlying HADA. Methods: We established a population cohort of individuals with HADA and assessed variations in metabolite composition. Plasm samples of four groups, including subjects staying at plain (P) and high altitude (H) as well as subjects suffering from HADA syndrome with almost no reaction (r3) and mild-to-moderate reaction (R3) after returning to plain from high altitude, were collected and analyzed by Liquid Chromatography-Mass Spectrometry metabolomic. Multivariate statistical analyses were used to explore significant differences and potential clinical prospect of metabolites. Result: Although significantly different on current HADAS diagnostic symptom score, there were no differences in 17 usual clinical indices between r3 and R3. Further multivariate analyses showed isolated clustering distribution of the metabolites among the four groups, suggesting significant differences in their metabolic characteristics. Through K-means clustering analysis, we identified 235 metabolites that exhibited patterns of abundance change consistent with phenotype of HADA syndrome. Pathway enrichment analysis indicated a high influence of polyunsaturated fatty acids under high-altitude conditions. We compared the metabolites between R3 and r3 and found 107 metabolites with differential abundance involved in lipid metabolism and oxidation, suggesting their potential role in the regulation of oxidative stress homeostasis. Among them, four metabolites might play a key role in the occurrence of HADA, including 11-beta-hydroxyandrosterone-3-glucuronide, 5-methoxyindoleacetate, 9,10-epoxyoctadecenoic acid, and PysoPC (20:5). Conclusion: We observed the dynamic variation in the metabolic process of HADA. Levels of four metabolites, which might be provoking HADA mediated through lipid metabolism and oxidation, were expected to be explore prospective indices for HADA. Additionally, metabolomics was more efficient in identifying environmental risk factors than clinical examination when dramatic metabolic disturbances underlying the difference in symptoms were detected, providing new insights into the molecular mechanisms of HADAS.

Shallow sea reverberation suppression based on a range azimuth patch matrix model.

Reverberation is the main background interference for active sonar detection in shallow sea. Reverberation suppression is crucial for enhancing the performance of active sonar. In this paper, a reverberation suppression method based on low-rank sparse decomposition is proposed. First, both the sparseness property of the targets and the non-local self-correlation property of the reverberation are used to construct a range azimuth patch matrix model. The reverberation suppression problem is then transformed into an optimization problem for the recovery of a low-rank sparse matrix. The validity of the proposed method is verified by using the measured data. Results show that, compared with the reverberation pre-whitening and sparse fractional Fourier transform methods, the proposed method significantly improves the reverberation suppression performance and achieves a better detection result when the signal-to-interference ratio is below -2 dB.

Biomarker Testing Disparities in Metastatic Colorectal Cancer.

Importance: Among patients with metastatic colorectal cancer (mCRC), data are limited on disparate biomarker testing and its association with clinical outcomes on a national scale. Objective: To evaluate the socioeconomic and demographic inequities in microsatellite instability (MSI) and KRAS biomarker testing among patients with mCRC and to explore the association of testing with overall survival (OS). Design, Setting, and Participants: This cohort study, conducted between November 2022 and March 2024, included patients who were diagnosed with mCRC between January 1, 2010, and December 31, 2017. The study obtained data from the National Cancer Database, a hospital-based cancer registry in the US. Patients with mCRC and available information on biomarker testing were included. Patients were classified based on whether they completed or did not complete MSI or KRAS tests. Exposure: Demographic and socioeconomic factors, such as age, race, ethnicity, educational level in area of residence, median household income, insurance type, area of residence, facility type, and facility location were evaluated. Main Outcomes and Measures: The main outcomes were MSI and KRAS testing between the date of diagnosis and the date of first-course therapy. Univariable and multivariable logistic regressions were used to identify the relevant factors in MSI and KRAS testing. The OS outcomes were also evaluated. Results: Among the 41 061 patients included (22 362 males [54.5%]; mean [SD] age, 62.3 [10.1] years; 17.3% identified as Black individuals, 78.0% as White individuals, 4.7% as individuals of other race, with 6.5% Hispanic or 93.5% non-Hispanic ethnicity), 28.8% underwent KRAS testing and 43.7% received MSI testing. A significant proportion of patients had Medicare insurance (43.6%), received treatment at a comprehensive community cancer program (40.5%), and lived in an area with lower educational level (51.3%). Factors associated with a lower likelihood of MSI testing included age of 70 to 79 years (relative risk [RR], 0.70; 95% CI, 0.66-0.74; P < .001), treatment at a community cancer program (RR, 0.74; 95% CI, 0.70-0.79; P < .001), rural residency (RR, 0.80; 95% CI, 0.69-0.92; P < .001), lower educational level in area of residence (RR, 0.84; 95% CI, 0.79-0.89; P < .001), and treatment at East South Central facilities (RR, 0.67; 95% CI, 0.61-0.73; P < .001). Similar patterns were observed for KRAS testing. Survival analysis showed modest OS improvement in patients with MSI testing (hazard ratio, 0.93; 95% CI, 0.91-0.96; P < .001). The median (IQR) follow-up time for the survival analysis was 13.96 (3.71-29.34) months. Conclusions and Relevance: This cohort study of patients with mCRC found that older age, community-setting treatment, lower educational level in area of residence, and treatment at East South Central facilities were associated with a reduced likelihood of MSI and KRAS testing. Highlighting the sociodemographic-based disparities in biomarker testing can inform the development of strategies that promote equity in cancer care and improve outcomes for underserved populations.

Equisetin protects from atherosclerosis in vivo by binding to STAT3 and inhibiting its activity.

Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound isolated from fungus of marine sponge origin, which has antibacterial, anti-inflammatory, lipid-lowering, and weight loss effects. Whether EQST has anti-atherosclerotic activity has not been reported. In this study, we revealed that EQST displayed anti- atherosclerosis effects through inhibiting macrophage inflammatory response, lipid uptake and foam cell formation in vitro, and finally ameliorated high-fat diet (HFD)-induced atherosclerosis in AopE-/- mice in vivo. Mechanistically, EQST directly bound to STAT3 with high-affinity by forming hydrophobic bonds at GLN247 and GLN326 residues, as well as hydrogen bonds at ARG325 and THR346 residues. EQST interacted with STAT3 physically, and functionally inhibited the transcription activity of STAT3, thereby regulating atherosclerosis. Therefore, these results supports EQST as a candidate for developing anti-atherosclerosis therapeutic agent.

Gestational organophosphate esters (OPEs) exposure in association with placental DNA methylation levels of peroxisome proliferator-activated receptors (PPARs) signaling pathway-related genes.

BACKGROUND: Organophosphate esters (OPEs) exposure could affect offspring health. However, the underlying mechanisms are not well documented. OBJECTIVES: Based on a birth cohort study, we aimed to investigate the associations among gestational OPEs exposure, placental DNA methylation levels of peroxisome proliferator-activated receptor (PPAR) signaling pathway-related genes, and fetal growth. METHODS: We measured the concentrations of eight OPE metabolites in maternal urine samples and neonatal anthropometric measurements in 733 mother-child pairs. In 327 placental samples, we assessed the DNA methylation levels of 14 genes which were involved in the PPARs signaling pathway and expressed in placenta. Multiple linear regression models were used to examine the associations of OPEs exposure with placental DNA methylation, and of OPEs and placental DNA methylation with neonatal anthropometric measurements. Causal mediation analyses were conducted to examine the potential mediating role of placental DNA methylation in the pathway between OPEs exposure and fetal growth. RESULTS: We observed a general pattern of OPEs exposure being associated with hypermethylation of candidate genes, with statistically significant associations identified for several OPEs with RXRA, ACAA1, ACADL, ACADM, PLTP, and NR1H3 methylation. Further, gestational exposure to BCIPP, DPP, BBOEP, ∑NCl-OPEs, and ∑OPEs tended to be associated with lower anthropometric measurements, with more significant associations observed on arm circumference, and abdominal and back skinfold thickness. Notably, RXRA, ACAA1, ACOX1, CPT2, ACADM, and NR1H3 methylation tended to be associated with lower neonatal anthropometric measurements, especially for abdominal and back skinfold thickness. Moreover, mediation analyses showed that 19.42 % of the total effect of DPP on the back skinfold thickness was mediated by changes in RXRA methylation, and there was a significant indirect effect of RXRA methylation. CONCLUSIONS: Gestational OPEs exposure could disrupt the placental DNA methylation levels of PPAR signaling pathway-related genes, which might contribute to the effect of OPEs on fetal growth.

Vancomycin-Loaded Sol-Gel System for In Situ Coating of Artificial Bone to Prevent Surgical Site Infections.

Surgical site infections (SSIs) related to implants have always been a major challenge for clinical doctors and patients. Clinically, doctors may directly apply antibiotics into the wound to prevent SSIs. However, this strategy is strongly associated with experience of doctors on the amount and the location of antibiotics. Herein, an in situ constructable sol-gel system is developed containing antibiotics during surgical process and validated the efficacy against SSIs in beagles. The system involves chitosan (CS), ß-glycerophosphate (ß-GP) and vancomycin (VAN), which can be adsorbed onto porous hydroxyapatite (HA) and form VAN-CS/ß-GP@HA hydrogel in a short time. The VAN concentration from VAN-CS/ß-GP@HA hydrogel is higher than minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) at the 21st day in vitro. In an in vivo canine model for the prevention of SSIs in the femoral condyle, VAN-CS/ß-GP@HA exhibits excellent biocompatibility, antimicrobial properties, and promotion of bone healing. In all, the CS/ß-GP instant sol-gel system is able to in situ encapsulate antibiotics and adhere on artificial bone implants during the surgery, effectively preventing SSIs related to implants.

The Role of Placental DNA Methylation at Reproduction-Related Genes in Associations between Prenatal Bisphenol Analogues Exposure and the Digit Ratio in Children at Age 4: A Birth Cohort Study.

Placental DNA methylation (DNAm) may be a potential mechanism underlying the effects of prenatal bisphenol analogues (BPs) exposure on reproductive health. Based on the Shanghai-Minhang Birth Cohort Study (S-MBCS), this study investigated associations of placental DNAm at reproduction-related genes with prenatal BPs exposure and children's digit ratios at age 4 using multiple linear regression models, and mediation analysis was further used to examine the mediating role of placental DNAm in the associations between prenatal BPs exposure and digit ratios among 345 mother-child pairs. Prenatal exposure to bisphenol A (BPA) was associated with hypermethylation at Protocadherin 8 (PCDH8), RBMX Like 2 (RBMXL2), and Sperm Acrosome Associated 1 (SPACA1), while bisphenol F (BPF) exposure was associated with higher methylation levels of Fibroblast Growth Factor 13 (FGF13). Consistent patterns were found in associations between higher DNAm at the 4 genes and increased digit ratios. Further mediation analysis showed that about 15% of the effect of BPF exposure on increased digit ratios was mediated by placental FGF13 methylation. In conclusion, the altered placental DNAm status might be a mediator underlying the feminizing effect of prenatal BPs exposure.

Perfluorooctane sulfonate promotes the migration of colorectal cancer cells by inducing epithelial-mesenchymal transition.

The potential association between colorectal cancer (CRC) and environmental pollutants is worrisome. Previous studies have found that some perfluoroalkyl acids, including perfluorooctane sulfonate (PFOS), induced colorectal tumors in experimental animals and promoted the migration of and invasion by CRC cells in vitro, but the underlying mechanism is unclear. Here, we investigated the effects of PFOS on the proliferation and migration of CRC cells and the potential mechanisms involving activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition (EMT). It was found that PFOS promoted the growth and migration of HCT116 cells at non-cytotoxic concentrations and increased the mRNA expression of the migration-related angiogenic cytokines vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). In a mechanistic investigation, the up-stream signal pathway PI3K/Akt-NF-κB was activated by PFOS, and the process was suppressed by LY294002 (PI3K/Akt inhibitor) and BAY11-7082 (NF-κB inhibitor) respectively, leading to less proliferation of HCT116 cells. Furthermore, matrix metalloproteinases (MMP) and EMT-related markers were up-regulated after PFOS exposure, and were also suppressed respectively by LY294002 and BAY11-7082. Moreover, the up-regulation of EMT markers was suppressed by a MMP inhibitor GM6001. Taken together, our results indicated that PFOS promotes colorectal cancer cell migration and proliferation by activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition. This could be a potential toxicological mechanism of PFOS-induced malignant development of colorectal cancer.

Molecular fingerprint and machine learning enhance high-performance MOFs for mustard gas removal.

Chemical warfare agents (CWAs), epitomized by the notoriously used mustard gas (HD), represent a class of exceptionally toxic chemicals whose airborne removal is paramount for battlefield safety. This study integrates high-throughput computational screening (HTCS) with advanced machine learning (ML) techniques to investigate the efficacy of metal-organic frameworks (MOFs) in adsorbing and capturing trace amounts of HD present in the air. Our approach commenced with a comprehensive univariate analysis, scrutinizing the impact of six distinct descriptors on the adsorption efficiency of MOFs. This analysis elucidated a pronounced correlation between MOF density and the Henry coefficient in the effective capture of HD. Then, four ML algorithms were employed to train and predict the performance of MOFs. The Random Forest (RF) algorithm demonstrates strong model learning and good generalization, achieving the best prediction result of 98.3%. In a novel exploratory stride, we incorporated a 166-bit MACCS molecular fingerprinting (MF) to identify critical functional groups within adsorbents. From the top 100 MOFs analyzed, 22 optimal functional groups were identified. Leveraging these insights, we designed three innovative substructures, grounded in these key functional groups, to enhance HD adsorption efficiency. In this work, the combination of MF and ML could provide a new direction for efficient screening of MOFs for the capture of HD in the air. The outcomes of this study offer substantial potential to revolutionize the domain of CWA capture. This represents a significant stride toward developing practical solutions that enhance both environmental protection and battlefield security.

Operation-friendly and accurate naked-eye observation assay for fast zoonotic echinococcosis and pulmonary tuberculosis monitoring in clinics.

Echinococcosis and tuberculosis are two common zoonotic diseases that can cause severe pulmonary infections. Early screening and treatment monitoring are of great significance, especially in areas with limited medical resources. Herein, we designed an operation-friendly and rapid magnetic enrichment-silver acetylene chromogenic immunoassay (Me-Sacia) to monitor the antibody. The main components included secondary antibody-modified magnetic nanoparticles (MNP-Ab2) as capture nanoparticles, specific peptide (EG95 or CFP10)-modified silver nanoparticles (AgNP-PTs) as detection nanoparticles, and alkyne-modified gold nanoflowers as chromogenic nanoparticles. Based on the magnetic separation and plasma luminescence techniques, Me-Sacia could completely replace the colorimetric assay of biological enzymes. It reduced the detection time to approximately 1 h and simplified the labor-intensive and equipment-intensive processes associated with conventional ELISA. Meanwhile, the Me-Sacia showed universality for various blood samples and intuitive observation with the naked eye. Compared to conventional ELISA, Me-Sacia lowered the detection limit by approximately 96.8 %, increased the overall speed by approximately 15 times, and improved sensitivity by approximately 7.2 %, with a 100 % specificity and a coefficient of variation (CV) of less than 15 %.

Lysophosphatidylcholine acyltransferase 1 suppresses nanoclustering and function of KRAS.

KRAS is frequently mutated in cancer, contributing to 20% of all human cancer especially pancreatic, colorectal and lung cancer. Signaling of the constitutively active KRAS oncogenic mutants is mostly compartmentalized to proteolipid nanoclusters on the plasma membrane (PM). Signaling nanoclusters of many KRAS mutants selectively enrich phosphatidylserine (PS) lipids with unsaturated sn-2 acyl chains, but not the fully saturated PS species. Thus, remodeling PS acyl chains may suppress KRAS oncogenesis. Lysophosphatidylcholine acyltransferases (LPCATs) remodel sn-2 acyl chains of phospholipids, with LPCAT1 preferentially generating the fully saturated lipids. Here, we show that stable expression of LPCAT1 depletes major PS species with unsaturated sn-2 chains while decreasing minor phosphatidylcholine (PC) species with the corresponding acyl chains. LPCAT1 expression more effectively disrupts the nanoclustering of oncogenic GFP-KRASG12V, which is restored by acute addback of exogenous unsaturated PS. LPCAT1 expression compromises signaling and oncogenic activities of the KRAS-dependent pancreatic tumor lines. LPCAT1 expression sensitizes human pancreatic tumor MiaPaCa-2 cells to KRASG12C specific inhibitor, Sotorasib. Statistical analyses of patient data further reveal that pancreatic cancer patients with KRAS mutations express less LPCAT1. Higher LPCAT1 expression also improves survival probability of pancreatic and lung adenocarcinoma patients with KRAS mutations. Thus, PS acyl chain remodeling selectively suppresses KRAS oncogenesis.

Intrinsic Stress Field for Liquid Surfaces.

The microscopic stress field inhomogeneity in the interfacial region adjacent to the liquid surface is the fundamental origin of the liquid surface tension, but because of broadening due to capillary fluctuations, a detailed molecular level understanding of the stress field remains elusive. In this work, we deconvolute the capillary fluctuations to reveal the intrinsic stress field and show that the atomic-level contributions to the surface tension are similar in functional form across a variety of monatomic systems. These contributions are confined to an interfacial region approximately 1.5±0.1 times the particle diameter for all systems studied. In addition, the intrinsic density and stress profiles show a strong spatial correlation that should be useful in the development of a statistical mechanical theory for the prediction of surface stress and surface tension.