Polystyrene nanoplastics induce cardiotoxicity by upregulating HIPK2 and activating the P53 and TGF-ß1/Smad3 pathways.

Nanoplastics (NPs) pollution has become a global environmental problem, raising numerous health concerns. However, the cardiotoxicity of NPs exposure and the underlying mechanisms have been understudied to date. To address this issue, we comprehensively evaluated the cardiotoxicity of polystyrene nanoplastics (PS-NPs) in both healthy and pathological states. Briefly, mice were orally exposed to four different concentrations (0 mg/day, 0.1 mg/day, 0.5 mg/day, and 2.5 mg/day) of 100-nm PS-NPs for 6 weeks to assess their cardiotoxicity in a healthy state. Considering that individuals with underlying health conditions are more vulnerable to the adverse effects of pollution, we further investigated the cardiotoxic effects of PS-NPs on pathological states induced by isoprenaline. Results showed that PS-NPs induced cardiomyocyte apoptosis, cardiac fibrosis, and myocardial dysfunction in healthy mice and exacerbated cardiac remodeling in pathological states. RNA sequencing revealed that PS-NPs significantly upregulated homeodomain interacting protein kinase 2 (HIPK2) in the heart and activated the P53 and TGF-beta signaling pathways. Pharmacological inhibition of HIPK2 reduced P53 phosphorylation and inhibited the activation of the TGF-ß1/Smad3 pathway, which in turn decreased PS-NPs-induced cardiotoxicity. This study elucidated the potential mechanisms underlying PS-NPs-induced cardiotoxicity and underscored the importance of evaluating nanoplastics safety, particularly for individuals with pre-existing heart conditions.

Bridge effect on charge transfer and energy transfer in fullerene-chromophore dyads.

Fullerene-chromophore dyads have attracted a great deal of research interest because these complexes can be potentially designed as nanoscale artificial photosynthetic centers, in which the chromophore and fullerene function as the electron donor and acceptor, respectively. The basic operation of this dyad-type artificial reaction center is photoinduced electron transfer from the donor to the acceptor. The fullerene and chromophore are usually covalently linked so that sufficient electronic coupling between these two moieties can facilitate the electron transfer. However, other deactivation pathways for the chromophore excited state, such as energy transfer to the fullerene, may reduce the quantum yield of the photoinduced electron transfer. Here, a series of C60-perylene dyads is exploited to interrogate the effect of the linkage on deactivation mechanisms of the chromophore excited state. For the C60-perylene dyads with a single or double bond bridge, we find that the decay of the singlet state of the chromophore is dominated by the electron transfer, and the corresponding time constant is determined to be 45 ps. On the other hand, for the dyad with a triple bond bridge, the singlet state of the chromophore is quickly quenched through energy transfer to fullerene, and the time constant is as short as 7.9 ps. Our finding suggests that the bond order of the bridge in the fullerene-chromophore dyads can be utilized to control the deactivation pathways of the excited state.

A tailored ratiometric fluorescent sensor based on CdTe and MgF2 quantum dots for trace N-ethylpentylone detection.

The development of low-cost and highly sensitive ratiometric fluorescence sensor, CdTe@MIPs/MgF2, for N-Ethylpentylone (NEP) detection in wastewater samples is described. In this system, CdTe@MIPs (λex = 370, λem = 570) are employed as the receptor and response unit for NEP, with MgF2 (λex = 370, λem = 470) as the reference signal to enhance stability. Under optimal conditions, the sensor shows fluorescent quenching response at 570 nm to NEP in linear range of 2-200 nM, with LOD of 0.6 nM. The sensor also demonstrates significant selectivity for NEP over other analogues and interferents, making it ideal for practical applications in wastewater analysis. This approach is potentially more cost-effective and sensitive than conventional mass spectrometry in detecting abused substances in sewage. Additionally, the MgF2 fluorescent nano-material was first-ever developed and investigated, which may be significant in future research.

Phosphorus-based soil prophylactics for managing Pb contamination in soil: Slow-release kinetics and microbiological effects.

Soil remediation poses significant challenges due to its spatial heterogeneity, surpassing the complexities of atmospheric and water remediation. This study introduces an innovative approach to prevent soil heavy metal pollution by developing three phosphorus slow-release heavy metal soil prophylactic agents (SLPs) - Sap-11, Sap-12, and Sap-21. At a liquid-to-solid ratio of 1:20, the three types of SLPs achieve phosphorus sustained slow release amounts of 1.586 g/L, 4.259 g/L, and 1.444 g/L within 30 days, respectively. Over a cultivation period of 120 days, after amendment with the three SLPs, the surface soil demonstrates stabilization capacities for Pb of 29.56 mg/g, 46.24 mg/g, and 25.77 mg/g, respectively, representing enhancements of 283.64 %, 500.12 %, and 250.74 % compared to the control. Firstly, the direct contribution of P (up to 3.778 mg/g) released from SLPs chemically binding with Pb, and secondly, a significant proportion of the indirect contribution originating from the microbial activity and soil organic matter. In summary, SLP emerges as an effective strategy for soil heavy metal management, stabilizing heavy metals by stimulating the soil's inherent physiological and biochemical reactions. This approach provides a practical solution for the application of P-containing materials and introduces novel perspectives for soil heavy metal management strategies.

How micro-/nano-plastics influence the horizontal transfer of antibiotic resistance genes - A review.

Plastic debris such as microplastics (MPs) and nanoplastics (NPTs), along with antibiotic resistance genes (ARGs), are pervasive in the environment and are recognized as significant global health and ecological concerns. Micro-/nano-plastics (MNPs) have been demonstrated to favor the spread of ARGs by enhancing the frequency of horizontal gene transfer (HGT) through various pathways. This paper comprehensively and systematically reviews the current study with focus on the influence of plastics on the HGT of ARGs. The critical role of MNPs in the HGT of ARGs has been well illustrated in sewage sludge, livestock farms, constructed wetlands and landfill leachate. A summary of the performed HGT assay and the underlying mechanism of plastic-mediated transfer of ARGs is presented in the paper. MNPs could facilitate or inhibit HGT of ARGs, and their effects depend on the type, size, and concentration. This review provides a comprehensive insight into the effects of MNPs on the HGT of ARGs, and offers suggestions for further study. Further research should attempt to develop a standard HGT assay and focus on investigating the impact of different plastics, including the oligomers they released, under real environmental conditions on the HGT of ARGs.

Ultra-high Q-factor quasi-BIC BaTiO3 metasurface for electro-optic modulation.

Metasurfaces play a crucial role in trapping electromagnetic waves with specific wavelengths, serving as a significant platform for enhancing light-matter interactions. In all kinds of dynamic modulation metasurfaces, electro-optic modulation metasurfaces have attracted much attention due to its advantages of fast, stable and high efficiency. In order to respond to the extremely weak refractive index change of the electro-optical effect of the materials, the metasurfaces are required to support optical signals with high Q values. The quasi-bound state in the continuum (Q-BIC) is often used to enhance the light-field modulation capability of metasurfaces and to improve the modulation sensitivity of electro-optic modulators due to its ability to generate high Q-factor resonances. However, the design of an electro-optic modulation metasurface that facilitates the application of voltage and achieves modulation efficiency of nearly 100% is still in urgent need of development. In this study, single-crystal BTO metasurfaces are modeled using finite-difference time-domain method, and the structural symmetry is broken to introduce a Q-BIC resonance to generate a high Q-factor optical signal of 2.45 × 104 for high-depth electro-optic modulation. By simulating an applied electric field of 143 V/mm on the metasurface, a slight refractive index change of BTO of 8 × 10-4 was produced, leading to an electro-optical intensity modulation depth of 100%. Furthermore, the nanostructure of the metasurface was carefully designed to facilitate nano-fabrication and voltage application, and it is ideal for the development of low-power, CMOS-compatible, and miniaturized electro-optic modulation devices. Although the results of this study are based on simulations, they provide a crucial theoretical basis and guidance for the realization of efficient and realistic design of dynamic metasurfaces.

Association between blood pressure control during aneurysm clipping and functional outcomes in patients with aneurysmal subarachnoid hemorrhage.

Objectives: We explored the relationship between blood pressure variability (BPV) during craniotomy aneurysm clipping and short-term prognosis in patients with aneurysmal subarachnoid hemorrhage to provide a new method to improve prognosis of these patients. Methods: We retrospectively analyzed the differences between patient groups with favorable modified Rankin Scale (mRS ≤ 2) and unfavorable (mRS > 2) prognosis, and examined the association between intraoperative BPV and short-term prognosis. Results: The intraoperative maximum systolic blood pressure (SBPmax, p = 0.005) and the coefficient of variation of diastolic blood pressure (DBPCV, p = 0.029) were significantly higher in the favorable prognosis group. SBPmax (OR 0.88, 95%CI 0.80-0.98) and Neu% (OR 1.22, 95%CI 1.03-1.46) were independent influence factors on prognosis. Patients with higher standard deviations of SBP (82.7% vs. 56.7%; p = 0.030), DBP (82.7% vs. 56.7%; p = 0.030), and DBPCV (82.7% vs. 56.7%; p = 0.030) had more favorable prognosis. Conclusion: Higher SBPmax (≤180 mmHg) during the clipping is an independent protective factor for a 90-day prognosis. These results highlight the importance of blood pressure (BP) control for improved prognosis; higher short-term BPV during clipping may be a precondition for a favorable prognosis.

Synergistic effects of superfine grinding and high hydrostatic pressure on the contents, distribution, digestive behaviors and antioxidant activities of polyphenols in barley leaves.

Barley leaves (BLs) naturally contained abundant phenolics, most of which are hardly completely released from food matrix during gastrointestinal digestion. Superfine grinding (SFG) and high hydrostatic pressure (HHP) are generally used to treat the functional plants due to their effectiveness to cell wall-breaking and improvement of nutraceutical bioavailability. Thus, this study investigated the synergistic effects of SFG and HHP (100, 300, 500 MPa/20 min) on the bioaccessbility of typical phenolics in BLs during the simulated in-vitro digestion. The results demonstrated that the highest bioaccessbility (40.98%) was found in the ultrafine sample with HHP at 500 MPa. CLSM and SEM confirmed SFG led to microstructurally rapture of BLs. Moreover, the recovery index of ABTS radical scavenging activity and FRAP of HHP-treated ultrafine and fine BLs samples maximumly increased by 53.62% and 9.61%, respectively. This study is expecting to provide the theoretical basis to improve the consumer acceptance of BLs.

The gut microbiota contributes to methamphetamine-induced reproductive toxicity in male mice.

Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.

Complete genome sequence of Lacticaseibacillus paracasei A02.

Lacticaseibacillus paracasei, a facultative anaerobic gram-positive bacterium, is commonly found in the gut of humans and animals, as well as in dairy products and plant ferments. Here, we report the complete genome sequence of L. paracasei A02, whose total genome length is 3,038,472 bp, with a GC content of 46.41%.

Zeolite-Templated Carbons Supported Rh and Ru Electrocatalysts for Highly Active Hydrogen Evolution Reaction.

Here, we report the systematical synthesis of zeolite-templated carbon (ZTC) supported Ru and Rh mono- or bi-metallic electrocatalysts towards hydrogen evolution reaction (HER). The zeolite A or ZSM-5 derived ZTC supports and metal sites were adjusted, and all electrocatalysts outperformed the commercial Pt/C electrocatalyst for HER performance. In particular, the RhRu/(ZTC/ZSM5) sample exhibited superior catalytic performance with the overpotential of 24.8 mV@10 mA ⋅ cm-2, and outstanding stability with 1 mV drop after 20000 cyclic voltammetry circles. This work offers a simple impregnation method for the synthesis of highly performed HER electrocatalysts supported on porous zeolite-templated carbon.

Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives.

Over 120 small-molecule kinase inhibitors (SMKIs) have been approved worldwide for treating various diseases, with nearly 70 FDA approvals specifically for cancer treatment, focusing on targets like the epidermal growth factor receptor (EGFR) family. Kinase-targeted strategies encompass monoclonal antibodies and their derivatives, such as nanobodies and peptides, along with innovative approaches like the use of kinase degraders and protein kinase interaction inhibitors, which have recently demonstrated clinical progress and potential in overcoming resistance. Nevertheless, kinase-targeted strategies encounter significant hurdles, including drug resistance, which greatly impacts the clinical benefits for cancer patients, as well as concerning toxicity when combined with immunotherapy, which restricts the full utilization of current treatment modalities. Despite these challenges, the development of kinase inhibitors remains highly promising. The extensively studied tyrosine kinase family has 70% of its targets in various stages of development, while 30% of the kinase family remains inadequately explored. Computational technologies play a vital role in accelerating the development of novel kinase inhibitors and repurposing existing drugs. Recent FDA-approved SMKIs underscore the importance of blood-brain barrier permeability for long-term patient benefits. This review provides a comprehensive summary of recent FDA-approved SMKIs based on their mechanisms of action and targets. We summarize the latest developments in potential new targets and explore emerging kinase inhibition strategies from a clinical perspective. Lastly, we outline current obstacles and future prospects in kinase inhibition.

Progress and Innovative Combination Therapies in Trop-2-Targeted ADCs.

Precise targeting has become the main direction of anti-cancer drug development. Trophoblast cell surface antigen 2 (Trop-2) is highly expressed in different solid tumors but rarely in normal tissues, rendering it an attractive target. Trop-2-targeted antibody-drug conjugates (ADCs) have displayed promising efficacy in treating diverse solid tumors, especially breast cancer and urothelial carcinoma. However, their clinical application is still limited by insufficient efficacy, excessive toxicity, and the lack of biological markers related to effectiveness. This review summarizes the clinical trials and combination therapy strategies for Trop-2-targeted ADCs, discusses the current challenges, and provides new insights for future advancements.

Chemical Composition of Essential Oil from Citrus reticulata Blanco cv. Chachiensis (Chachi) and Its Anti-Mosquito Activity against Pyrethroid-Resistant Aedes albopictus.

The overuse of synthetic insecticides has led to various negative consequences, including insecticide resistance, environmental pollution, and harm to public health. This may be ameliorated by using insecticides derived from botanical sources. The primary objective of this study was to evaluate the anti-mosquito activity of the essential oil (EO) of Citrus reticulata Blanco cv. Chachiensis (Chachi) (referred to as CRB) at immature, semi-mature, and mature stages. The chemical compositions of the CRB EO were analyzed using GC-MS. The main components were identified to be D-limonene and γ-terpinene. The contents of D-limonene at the immature, semi-mature, and mature stages were 62.35%, 76.72%, and 73.15%, respectively; the corresponding contents of γ-terpinene were 14.26%, 11.04%, and 11.27%, respectively. In addition, the corresponding contents of a characteristic component, methyl 2-aminobenzoate, were 4.95%, 1.93%, and 2.15%, respectively. CRB EO exhibited significant larvicidal activity against Aedes albopictus (Ae. albopictus, Diptera: Culicidae), with the 50% lethal doses being 65.32, 61.47, and 65.91 mg/L for immature, semi-mature, and mature CRB EO, respectively. CRB EO was able to inhibit acetylcholinesterase and three detoxification enzymes, significantly reduce the diversity of internal microbiota in mosquitoes, and decrease the relative abundance of core species within the microbiota. The present results may provide novel insights into the utilization of plant-derived essential oils in anti-mosquitoes.

Active-matrix digital microfluidics design for field programmable high-throughput digitalized liquid handling.

Digital liquid sample handling is an enabling tool for cutting-edge life-sciences research. We present here an active-matrix thin-film transistor (TFT) based digital microfluidics system, referred to as Field Programmable Droplet Array (FPDA). The system contains 256 × 256 pixels in an active area of 10.65 cm2, which can manipulate thousands of addressable liquid droplets simultaneously. By leveraging a novel TFT device and circuits design solution, we manage to programmatically manipulate droplets at single-pixel level. The minimum achievable droplet volume is around 0.5 nL, which is two orders of magnitude smaller than the smallest droplet ever reported on active-matrix digital microfluidics. The movement of droplets can be either pre-programmed or controlled in real-time. The FPDA system shows great potential of the ubiquitous thin-film electronics technology in digital liquid handling. These efforts will make it possible to create a true programmable lab-on-a-chip device to enable great advances in life science research.

Surface-Initiated Polymerization with an Initiator Gradient: A Monte Carlo Simulation.

Due to the difficulty of accurately characterizing properties such as the molecular weight (Mn) and grafting density (σ) of gradient brushes (GBs), these properties are traditionally assumed to be uniform in space to simplify analysis. Applying a stochastic reaction model (SRM) developed for heterogeneous polymerizations, we explored surface-initiated polymerizations (SIPs) with initiator gradients in lattice Monte Carlo simulations to examine this assumption. An initial exploration of SIPs with 'homogeneously' distributed initiators revealed that increasing σ slows down the polymerization process, resulting in polymers with lower molecular weight and larger dispersity (D) for a given reaction time. In SIPs with an initiator gradient, we observed that the properties of the polymers are position-dependent, with lower Mn and larger D in regions of higher σ, indicating the non-uniform properties of polymers in GBs. The results reveal a significant deviation in the scaling behavior of brush height with σ compared to experimental data and theoretical predictions, and this deviation is attributed to the non-uniform Mn and D.

A portable transistor immunosensor for fast identification of porcine epidemic diarrhea virus.

Widespread distribution of porcine epidemic diarrhea virus (PEDV) has led to catastrophic losses to the global pig farming industry. As a result, there is an urgent need for rapid, sensitive and accurate tests for PEDV to enable timely and effective interventions. In the present study, we develop and validate a floating gate carbon nanotubes field-effect transistor (FG CNT-FET)-based portable immunosensor for rapid identification of PEDV in a sensitive and accurate manner. To improve the affinity, a unique PEDV spike protein-specific monoclonal antibody is prepared by purification, and subsequently modified on FG CNT-FET sensor to recognize PEDV. The developed FET biosensor enables highly sensitive detection (LoD: 8.1 fg/mL and 100.14 TCID50/mL for recombinant spike proteins and PEDV, respectively), as well as satisfactory specificity. Notably, an integrated portable platform consisting of a pluggable FG CNT-FET chip and a portable device can discriminate PEDV positive from negative samples and even identify PEDV and porcine deltacoronavirus within 1 min with 100% accuracy. The portable sensing platform offers the capability to quickly, sensitively and accurately identify PEDV, which further points to a possibility of point of care (POC) applications of large-scale surveillance in pig breeding facilities.

Association of testosterone with myocardial infarction and severity of coronary artery disease among male patients.

Background: Coronary heart disease (CHD) remains a leading cause of morbidity and mortality, particularly in aging populations. Men typically exhibit higher rates of CHD compared to women, with testosterone levels inversely associated with cardiovascular risk. This study investigates the relationship between testosterone levels and angiographically confirmed CHD, disease severity, and myocardial infarction (MI) among CHD cases. Methods: A cohort of 1724 male patients undergoing diagnostic or interventional coronary angiography was examined. Demographic, clinical, and biochemical data were collected, including serum total testosterone levels. The severity of CHD was assessed using the Gensini score, and MI cases were diagnosed according to World Health Organization criteria. Results: Results revealed significant differences in testosterone levels among CHD subtypes, particularly between MI and unstable angina/stable angina groups (p < 0.001). Testosterone levels were inversely correlated with CHD severity, as evidenced by the Gensini score (Pearson coefficient = -0.062, P = 0.004). Cross-validation random forest analysis demonstrated the significant contribution of testosterone to CHD severity discrimination (p < 0.05). Conclusions: There is an association between testosterone and a predisposition to severe CAD indicated by Gensini score and myocardial infarction.

Potential effects of soil petroleum contamination on decomposition of Artemisia annua plant litter.

The accumulation of petroleum contaminants in phytoremediating plants can significantly impact the decomposition of their litter. However, the mechanisms underlying these effects and the potential influence of the contaminant concentration remain unclear. In this study, litter from Artemisia annua plants grown in soil with varying concentrations of petroleum (0, 15, 30, and 45 g kg-1) was collected. The litter samples were then inoculated with soil microorganisms and subjected to an indoor simulation of decomposition under controlled temperature and humidity conditions. Changes in the chemical properties, activities of decomposition-related enzymes in the litter, and decomposition rates were measured. Additionally, structural equation modeling was employed to analyze the mechanism through which soil petroleum contamination affects litter decomposition. The findings revealed several key points: (1) increasing soil petroleum contamination tended to reduce the concentration of carbon and nitrogen in litter while increasing those of lignin and total petroleum hydrocarbons (TPH). (2) Soil petroleum contamination tended to increase the activities of both total lignocellulases and total nutrient cycling-related enzymes in litter. (3) Soil petroleum contamination might indirectly inhibit the activity of lignocellulases by increasing the concentration of lignin and TPH in litter. However, it might also directly accelerate the activity of these enzymes, resulting in contradictory effects on litter decomposition. (4) Finally, A. annua litter produced in soil contaminated with 15 and 30 g kg-1 of petroleum exhibited significantly lower decomposition rates than that from uncontaminated soil.

Double synergic chitosan-coated poly (lactic-co-glycolic) acid nanospheres loaded with nucleic acids as an intranasally administered vaccine delivery system to control the infection of foot-and-mouth disease virus.

BACKGROUND & AIMS: The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial. PATIENTS AND METHODS: Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL). Then, the constructed plasmid was electrostatically attached to mannose-modified chitosan-coated poly(lactic-co-glycolic) acid (PLGA) nanospheres (MCS-PLGA-NPs) to obtain an active nasal vaccine targeting the mannose-receptor on the surface of antigen-presenting cells (APCs). RESULTS: The MCS-PLGA-NPs loaded with pTB-FL not only induced a local mucosal immune response, but also induced a systemic immune response in mice. More importantly, the nasal vaccine afforded an 80% protection rate against a highly virulent FMDV strain (AF72) when it was subcutaneously injected into the soles of the feet of guinea pigs. CONCLUSIONS: The nasal vaccine prepared in this study can effectively induce a cross-protective immune response against the challenge with FMDV of same serotype in animals and is promising as a potential FMDV vaccine.