Pilot analysis of tire tread characteristics and associated tire-wear particles in vehicles produced across distinct time periods.

Owing to stringent vehicle emission regulations and the shifting automotive landscape towards clean-energy vehicles, the emission of non-exhaust tire-wear particles and its implications for microplastic contamination have garnered substantial attention, emerging as a focal point of research interest. Unlike traditional source apportionment methods involving direct environmental sampling, this study focuses on the physical and chemical attributes of tire treads, the tread temperature changes, and the tire-wear particle emissions of three light-duty vehicles manufactured between 2011 and 2021. This study advances the understanding of the effects of tire properties on particle emissions, which provides preliminary information on low-wear tires. The results show that tire-wear particle emissions, mainly composed of ultrafine particles in terms of number, heavily depend on the elevated tread temperatures. The change in tread temperature is influenced not only by the initial tread temperature but also by tread pyrolysis characteristics. Ca, Mg, and Zn are abundantly contained in the tire tread and tire-wear particles.

Causal association between rheumatoid arthritis and an increased risk of age-related macular degeneration: A Mendelian randomization study.

This study's goal is to evaluate if there is a causal connection between rheumatoid arthritis (RA) and age-related macular degeneration (AMD), despite past epidemiological studies suggesting an association between the 2 disorders. The impact of RA on AMD is still unknown. Mendelian randomization (MR) was utilized in this study to assess the two-sample causal relationship between RA and AMD. Summary data from GWAS for RA and AMD in individuals with all European ancestries were gathered using the IEU GWAS database. The GWAS summary statistics of RA (14,361 RA patients and 43,923 healthy controls) and AMD (14,034 AMD patients and 91,214 controls participated) were obtained from the IEU GWAS database. After identifying suitable instrumental variables in line with the 3 MR assumptions, we conducted MR using the Mendelian randomization-Egger (MR-Egger), weighted median, and inverse variance weighting techniques. The MR-Egger intercept and MR-Polyvalent Residuals and Outliers methods were used to investigate the effects of horizontal pleiotropy. The leave-one-out strategy was used to prevent bias caused by certain single nucleotide polymorphisms. Sensitivity analysis was used to detect the heterogeneity. Using 50 single nucleotide polymorphisms as instrumental variables, this study examined the relationship between RA and AMD and discovered that RA increased the risk of AMD (inverse variance weighting odds ratio [OR] = 1.056, 95% confidence interval [CI] = 1.02-1.09, P = 5.44E-04; weighted median OR = 1.085, 95% CI = 1.04-1.14, P = 4.05E-04; MR-Egger OR = 1.074, 95% CI = 1.01-1.14, P = 2.18E-2). The current investigation demonstrated a causal link between AMD and RA. RA increased the risk of AMD. It is advised that future research concentrate on the processes underlying the relationship between RA and AMD.

Integrative omics analysis elucidates the genetic basis underlying seed weight and oil content in soybean.

Synergistic optimization of key agronomic traits by traditional breeding has dramatically enhanced crop productivity in the past decades. However, the genetic basis underlying coordinated regulation of yield- and quality-related traits remains poorly understood. Here, we dissected the genetic architectures of seed weight and oil content by combining genome-wide association studies (GWAS) and transcriptome-wide association studies (TWAS) using 421 soybean (Glycine max) accessions. We identified 26 and 33 genetic loci significantly associated with seed weight and oil content by GWAS, respectively, and detected 5,276 expression quantitative trait loci (eQTLs) regulating expression of 3,347 genes based on population transcriptomes. Interestingly, a gene module (IC79), regulated by two eQTL hotspots, exhibited significant correlation with both seed weigh and oil content. Twenty-two candidate causal genes for seed traits were further prioritized by TWAS, including Regulator of Weight and Oil of Seed 1 (GmRWOS1), which encodes a sodium pump protein. GmRWOS1 was verified to pleiotropically regulate seed weight and oil content by gene knockout and overexpression. Notably, allelic variations of GmRWOS1 were strongly selected during domestication of soybean. This study uncovers the genetic basis and network underlying regulation of seed weight and oil content in soybean and provides a valuable resource for improving soybean yield and quality by molecular breeding.

A quaternary ammonium-based nanosystem enables delivery of CRISPR/Cas9 for cancer therapy.

Genome editing mediated by CRISPR/Cas9 is an attractive weapon for cancer therapy. However, in vivo delivery of CRISPR/Cas9 components to achieve therapeutic efficiency is still challenging. Herein, a quaternary ammonium-functionalized poly(L-lysine) and a cholesterol-modified PEG (QNP) were self-assembled with a negatively charged CRISPR Cas9/sgRNA ribonucleoprotein (RNP) to form a ternary complex (QNP/RNP). Such a delivery system of QNP exhibited multiplex genome editing capabilities in vitro (e.g., the GFP gene and the PLK1 gene). In addition, QNP/RNPPLK1 containing PLK1 sgRNA led to 30.99% of genome editing efficiency in MCF-7 cells with negligible cytotoxicity of the carrier. QNP/RNPPLK1, which was capable of simultaneously inhibiting cell proliferation, mediating cell cycle arrest and downregulating expression of PLK1, held great in vitro therapeutic efficiency. Moreover, QNP/RNPPLK1 exhibited outstanding accumulation in tumors and high biocompatibility in vivo. In an MCF-7 xenograft animal model, QNP/RNPPLK1 showed excellent anti-tumor efficacy and achieved 17.75% indels ratio. This work showcases the successful delivery of CRISPR Cas9/sgRNA RNP with enhanced genome editing efficiency and provides a potential on-demand strategy for cancer therapy.

Policy instruments facilitate China's COVID-19 work resumption.

Governments worldwide have announced stimulus packages to remobilize the labor force after COVID-19 and therefore to cope with the COVID-19-related recession. However, it is still unclear how to facilitate large-scale work resumption. This paper aims to clarify the issue by analyzing the large-scale prefecture-level dataset of human mobility trajectory information for 320 million workers and about 500,000 policy documents in China. We model work resumption as a collective behavioral change due to configurations of capacity, motivation, and policy instruments by using qualitative comparative analysis. We find that the effectiveness of post-COVID-19 recovery stimulus varied across China depending on the fiscal and administrative capacity and the policy motivation of the prefecture. Subnational fiscal and procurement policies were more effective for the wholesale and retail sector and the hotel and catering sector, whereas the manufacturing and business services sectors required more effort regarding employment policies. Due to limited prefectural capacity and wavering policy motivation, the simultaneous adoption of fiscal, employment, and procurement policy interventions endangered post-COVID-19 work resumption. We highlight the necessity of tailored postcrisis recovery strategies based on local fiscal and administrative capacity and the sectoral structure.

Exosome-mediated delivery of superoxide dismutase for anti-aging studies in Caenorhabditis elegans.

Aging is a dynamic and progressive process mediated by reactive oxygen species (ROS), and the antioxidant enzyme superoxide dismutase (SOD) can effectively scavenge ROS to extend longevity. However, the instability and impermeability of native enzyme limit its in vivo biomedical application. Currently, exosome as protein carriers attracts considerable attention in the disease treatment owing to low immunogenicity and high stability. Herein, SOD was encapsulated into exosomes via mechanical extrusion with saponin permeabilization to obtain SOD-loaded EXO (SOD@EXO). SOD@EXO with a hydrodynamic diameter of 101.7 ± 5.6 nm could scavenge excessive ROS and protect the cells from oxidative damage induced by 1-methyl-4-phenylpyridine. Compared with native SOD, SOD@EXO significantly extended the lifespan of N2 wild-type Caenorhabditis elegans under normal conditions. Moreover, SOD@EXO improved the resistance against heat and oxidative stress, leading to notable survival ratio under these hostile conditions. Overall, the exosome-mediated delivery of SOD could reduce ROS level and delay aging in C. elegans model, thereby providing potential strategies to treat ROS-related diseases in future.

Brain functional specialization in obsessive-compulsive disorder associated with neurotransmitter profiles.

BACKGROUND: Cerebral specialization is an important functional architecture of the human brain. Abnormal cerebral specialization may be the underlying pathogenesis of obsessive-compulsive disorder (OCD). Resting-state functional magnetic resonance imaging (rs-fMRI) was used to show that the specialization pattern of OCD was of great significance for early warning and precise intervention of the disease. METHOD: The autonomy index (AI) based on the rs-fMRI was calculated to compare brain specializations between 80 OCD patients and 81 matched healthy controls (HCs). In addition, we also correlated the AI alteration patterns with neurotransmitter receptor/transporter densities. RESULTS: OCD patients showed increased AI in the right insula and right superior temporal gyrus when compared with HCs. In addition, AI differences were associated with serotonin receptors (5-HT1AR and 5HT4R), dopamine D2 receptors, norepinephrine transporters, and metabotropic glutamate receptor densities. LIMITATIONS: Drug effect; cross-sectional study design; the selection of positron emission tomography template. CONCLUSIONS: This study showed abnormal specialization patterns in OCD patients, which may lead to the elucidation of the underlying pathological mechanism of the disease.

Responses of bacterial community and N-cycling functions stability to different wetting-drying alternation frequencies in a riparian zone.

Wetting-drying alternation (WD) of the soil is one of the key characteristics of riparian zones shaped by dam construction, profoundly impacting the soil microenvironment that determines the bacterial community. Knowledge concerning the stability of bacterial community and N-cycling functions in response to different frequencies of WD remains unclear. In this study, samples were taken from a riparian zone in the Three Gorges Reservoir (TGR) and an incubation experiment was conducted including four treatments: constant flooding (W), varied wetting-drying alternation frequencies (WD1 and WD2), and constant drying (D) (simulating water level of 145 m, 155 m, 165 m, and 175 m in the riparian zone respectively). The results revealed that there was no significant difference in the diversity among the four treatments. Following the WD1 and WD2 treatments, the relative abundances of Proteobacteria increased, while those of Chloroflexi and Acidobacteriota decreased compared to the W treatment. However, the stability of bacterial community was not affected by WD. Relative to the W treatment, the stability of N-cycling functions estimated by resistance, which refers to the ability of functional genes to adapt to changes in the environment, decreased following the WD1 treatment, but showed no significant change following the WD2 treatment. Random forest analysis showed that the resistances of the nirS and hzo genes were core contributors to the stability of N-cycling functions. This study provides a new perspective for investigating the impacts of wetting-drying alternation on soil microbes.

Gram-scale preparation of quercetin supramolecular nanoribbons for intestinal inflammatory diseases by oral administration.

Gastrointestinal (GI) tract, which possesses the largest surface area of mucosa in the body, is easily suffered from inflammatory damages under the exposure of external stimulations. Excessive reactive oxygen species (ROS) production and continuous oxidative stress in intestines can elicit local mucosal injury, accelerate mucosal ulceration, and amplify the inflammatory response. Thereby, antioxidant therapy is a potential strategy against intestinal inflammatory diseases. Herein, we demonstrate the gram-scale preparation of quercetin supramolecular nanoribbons (SNRs) by using free quercetin molecules as the sole building block for preventing and treating intestinal inflammatory diseases. Unlike current clinical medicines, which mainly confront with poor response and severe adverse effects via bloodstream delivery, our quercetin SNRs possess an excellent antioxidant activity in the harsh environments of GI tract, a relative long retention time in GI tract, an admirable metabolism in GI tract without burdening other organs, and a specific adhesion to the inflamed intestinal epithelium via electrostatic interactions. These advantages strongly guarantee the applications of quercetin SNRs as oral medicines for intestinal inflammatory diseases. After establishing the models of intestinal inflammatory diseases caused by irradiation and drug stimulations, our quercetin SNRs exhibit the promising protective and therapeutic effects for radiation-induced acute enteritis and dextran sulfate sodium (DSS)-induced acute colitis. Because the super easy and fast preparation procedure and the nearly 100% loading capacity of quercetin SNRs, the current work provides a supramolecular nanomedicine with great clinical translation potential against intestinal inflammatory diseases.

Correction: Zhang et al. The Effect of Non-Invasive Brain Stimulation on the Downregulation of Negative Emotions: A Meta-Analysis. Brain Sci. 2022, 12, 786.

In the original article [...].

The Effect of Non-Invasive Brain Stimulation on the Downregulation of Negative Emotions: A Meta-Analysis.

(1) Background: Emotion regulation (ER) is regarded as a core treatment target for depression and other mental illnesses. In recent years, non-invasive brain stimulation (NIBS) has been extensively used as an intervention for mental illnesses, but there has been no systematic review conducted regarding its effect on emotion regulation. Therefore, we conducted a meta-analysis of the effectiveness of NIBS for emotion regulation; (2) Methods: Systematic searches were conducted in Embase, Web of Science, PubMed, and Cochrane Library. We analyzed the effects of NIBS on tasks assessing emotion regulation using a random-effects model, and further explored the moderating role of the following factors on transcranial direct current stimulation (tDCS) studies by conducting subgroup analyses and meta-regression: target electrode placement, return electrode placement, current intensity, target electrode size, and duration of intervention; (3) Results: A total of 17 studies were included. Our meta-analysis indicated a small but significant effect of NIBS on the downregulation of negative emotions. Separate analyses indicated that repetitive transcranial magnetic stimulation (rTMS) had a medium and significant effect on the downregulation of negative emotions, whereas tDCS had no significant effect. Subgroup analyses showed that the effect of tDCS was moderated by target and return electrode placemen; (4) Conclusions: These results indicate that NIBS had a positive effect on the downregulation of negative emotions. The stimulation protocols should be carefully considered and the underlying mechanisms should be further explored.

Multi-analytical approach to the mural painting from an ancient tomb of Ming Dynasty in Jiyuan, China: Characterization of materials and techniques.

The pigments, surface deposition, preparatory layer and support from a mural painting tomb of Ming Dynasty (1368-1644 CE) were first time analyzed by micro-Raman, Fourier-transform Infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscope with energy-dispersive X-ray microanalysis (SEM-EDX), thermogravimetry and differential scanning calorimetry (TG-DSC) to reach a better understanding of the composition of the materials and the techniques adopted. All the pigments were identified, including hematite, cinnabar, malachite, yellow ochre, calcite and carbon black. The preparatory layer was found to be prepared by fine lime mortar with cotton fiber inside. The crystalline depositions on the mural painting were identified as calcite and dolomite originated from the lime-based preparatory layer. The support was found to be constructed with sticky rice lime mortar with several kinds of additives. The original lime stone was demonstrated to be magnesium-rich and the carbonization results were also discussed. These results revealed significant information on the materials and techniques used to build mural painting tomb in Ming Dynasty. This will benefit the further restoration and conservation works and also provide a methodology solution for the scientific analysis of ancient tomb mural paintings.

A carrier-free photodynamic nanodrug to enable regulation of dendritic cells for boosting cancer immunotherapy.

Immune response is initiated by dendritic cells (DCs), where the cross-presentation of antigens by DCs determines the activating of cytotoxic T cells. However, the efficacy of DCs-initiated immune response is governed by multiple (cascade) steps of immunogenic cell death (ICD), recruitment of DCs, and cross-presentation of DCs. It is urgent but challenging to achieve a platform for simultaneously regulating these multiple steps, amplifying the immune response against tumors. Herein, we reported a photodynamic nanodrug enabling simultaneous regulation of these multiple steps for realizing powerful immune response. The nanodrug was designed by the co-assembling of chlorin e6 (Ce6), celecoxib and 6-thio-2'-deoxyguanosine (6-thio-dG). In our nanodrug, Ce6 enables induction of ICD, while celecoxib down-regulates the prostaglandin E2 (PGE2) for promoting recruitment of DCs enabled by chemokine CCL5 produced from natural killer (NK) cells. Moreover, 6-thio-dG triggers DNA damages in the tumor cells, which in turn activates STING/interferon I pathway for enhancing the cross-presentation ability of DCs. Therefore, an amplified immune therapeutic effect against tumors is achieved, thanks to the simultaneous regulation of these multiple steps. The nanodrug effectively inhibits tumor growth and postoperative recurrence, demonstrating a new approach for boosting immune response initiated by DCs in cancer therapy. STATEMENT OF SIGNIFICANCE: The dendritic cells (DCs)-initiated immune response against tumors is dominated by multiple (cascade) steps including the process of (I) immunogenic cell death (ICD), (II) recruitment of DCs, and (III) cross-presentation of antigens by DCs. Based on this, it is urgent to design a nanoplatform enabling simultaneous regulation of these multiple steps for achieving a potent therapeutic efficacy. A carrier-free photodynamic nanodrug, engineered by a co-assembling approach, was designed to regulate DCs for realizing a powerful DCs-initiated immune response against tumors, thanks to the simultaneous regulation of the above multiple steps. Our nanodrug demonstrated a boosted immune response against tumors, powerfully suppressing primary/abscopal tumor growth and postoperative recurrence, which offers a conceptually innovative strategy for amplifying immunity against tumors.

Boosting the Ion Mobility in Solid Polymer Electrolytes Using Hollow Polymer Nanospheres as an Additive.

Solid polymer electrolytes (SPEs) possess improved thermal and mechanical stability as safe energy storage devices. However, their low ion mobilities and poor electrochemical stabilities still hinder the wide industrial application of SPEs. Herein, we introduce an SPE design that provides an enormous number of electrochemically stable pathways and space for lithium-ion transport, blending polymer (polydopamine) hollow nanospheres with an inactive inorganic template into a poly(ethylene oxide) (PEO) and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) based SPE. Hollow silica acts as a template for polydopamine processing a large contact area with the polymer electrolyte, and the interface between the polymer electrolyte and hollow composite fillers provides amounts of ion transport channels. In addition, theoretical calculations reveal a strong adsorption between polydopamine and TFSI-, which suppresses the TFSI- motion and meanwhile facilitates the selective Li+ transport. The hollow polydopamine can serve as a versatile platform for anion trapping and has large compatible and stable depression for a well-defined ion transfer interface layer, forming a three-in-one nanocomposite for the enhancement of ionic conductivity with no sacrifice of the mechanical properties. Experimental data confirmed the high mobility of ions within the composite electrolyte with an ionic conductivity of 0.189 mS cm-1 in comparison to the SPE without additives (0.105 mS cm-1) at 60 °C. The mobility of the Li+ increases after adding the polymer-coated inorganic additives, associated with a noticeable enlargement of the electrochemical window. Furthermore, an all-solid-state Li/LiFePO4 battery with a hollow polydopamine nanoparticle-polymer composite electrolyte shows long life, high reversible capacity (134.9 mAh g-1), and high capacity retention (97.2%) after 205 cycles at 0.2 C.

Evaporative emission characteristics of high-mileage gasoline vehicles.

Evaporative emissions of vehicles are an essential source of atmospheric volatile organic compounds (VOCs), contributing to ozone contamination, especially in urban areas. Due to the outdated standards under which in-use vehicles were constructed and the ageing of control devices, high-mileage vehicles tend to produce an enormous amount of evaporative emissions. In this study, evaporative emissions from two high-mileage light-duty gasoline vehicles were quantified using VT-SHED, and their ozone-forming potential (OFP) values were calculated based on the identified VOC species. The results show that VOCs with high boiling points are released at low rates when the temperature inside the VT-SHED ranges from 20 to 28 °C. The release rates of all VOC species increase when the VT-SHED temperature is 28-35 °C. Diurnal loss dominates evaporative emissions from high-mileage gasoline vehicles, with the levels of VOCs quantified within this stage being 3-fold higher than those during the hot-soak stage. Only during the hot-soak stage, C11-C16 n-alkanes occupy an overall increased portion in the identified VOC inventory. OFP values of the two high-mileage vehicles exceeded 600.0 mgO3/day during the 48-h diurnal-loss tests. The specific reactivity (SR) values of the diurnal-loss VOCs are deemed more relevant to fuel compositions because the two vehicles have the same fuel yield and close SR values of approximately 4.3 mgO3/mgVOCs, despite different certification standards, potentially allowing for the use of unified SR values to ease the estimation of the ozone contamination of evaporative emissions from in-use fleets.

A self-amplifying nanodrug to manipulate the Janus-faced nature of ferroptosis for tumor therapy.

Ferroptosis, an unusual non-apoptotic cell death caused by the iron-dependent accumulation of lipid peroxide, enables the flexible design of an antitumor platform. Specifically, as a positive role, ferroptosis can induce an immune response accompanied with the interferon-γ (IFN-γ)-triggered disruption of the glutathione peroxidase 4 pathway for cascade enhancement of ferroptotic cell death and ferroptosis-induced immunotherapeutic efficacy. However, as a negative role, ferroptosis also triggers inflammation-associated immunosuppression by up-regulation of the cyclooxygenase-2/prostaglandin E2 pathway and IFN-γ-associated adaptive immune resistance by up-regulation of programmed death ligand-1 (PD-L1), impeding the antitumor efficacy of multiple immune cells by immune escape. Negative and positive roles endow ferroptosis with a Janus-faced nature. It is urgent to manipulate the Janus-faced nature of ferroptosis for eliciting the maximized ferroptotic therapeutic efficacy. Herein, a self-amplifying nanodrug (RCH NPs) was designed by co-assembling hemin (ferric porphyrin), celecoxib (anti-inflammatory drug) and roscovitine (cyclin-dependent kinase 5 inhibitor) with the assistance of human serum albumin for reprograming the Janus-faced nature of ferroptosis. During hemin-triggered ferroptosis, celecoxib disrupted the inflammation-related immunosuppression while roscovitine destroyed the IFN-γ-induced up-regulation of PD-L1 via the genetic blockade effect. The RCH NPs thus demonstrated superior therapeutic effects on tumors, thanks to self-amplifying ferroptotic immunotherapy. Our work offers a conceptually innovative strategy for harnessing ferroptosis against tumors.

A heme-regulatable chemodynamic nanodrug harnessing transcription factor Bach1 against lung cancer metastasis.

Non-small cell lung cancer (NSCLC) is a type of cancer dominated by metastasis-induced death. The transcription factor BTB and CNC homology 1 (Bach1) regulates almost all metastasis steps by activating the transcription of critical metastatic genes. It is urgent to engineer a nanodrug enabling regulation of Bach1 against tumor metastasis. Herein, a minimalist nanodrug integrating chemodynamic therapy (CDT) and Bach1 degradation was reported to prevent metastasis of NSCLC. The nanodrug was achieved by self-assembly of ferrocene (Fc) and Tin protoporphyrin IX (TinPPIX). In our nanodrug, Fc not only triggers the production of highly cytotoxic ∙OH for tumor ablation via Fenton reaction, but also induces heme release from heme-containing proteins to stimulate Bach 1 degradation. Moreover, TinPPIX further augments the free heme level along with amplifies the CDT efficacy by disabling heme oxygenase-1 (HO-1)-mediated heme conversion into antioxidative bilirubin. The results showed that, compared with control group, TinPPIX/Fc nanodrug caused a four-fold increase in heme level, which triggered remarkable Bach1 degradation in Fbxo22-mediated manner and successfully inhibited Bach1-dominated metastasis. Therefore, this nanodrug could powerfully impeded NSCLC progression and metastasis, offering an innovative heme-regulatable chemodynamic therapeutic approach for lung cancer with strong metastasis capability.

Development of an in vitro carcinogenesis model of human papillomavirus-induced cervical adenocarcinoma.

Cervical adenocarcinoma (ADC) is the second most common pathological subtype of cervical cancer after squamous cell carcinoma. It accounts for approximately 20% of cervical cancers, and the incidence has increased in the past few decades, particularly among young patients. The persistent infection of high-risk human papillomavirus (HPV) is responsible for most cervical ADC. However, almost all available in vitro models are designed to study the carcinogenesis of cervical squamous cell carcinoma. To gain better insights into molecular background of ADC, we aimed to establish an in vitro carcinogenesis model of ADC. We previously reported the establishment of an in vitro model for cervical squamous cell carcinoma by introducing defined viral and cellular oncogenes, HPV16 E6 and E7, c-MYC, and activated RAS to human cervical keratinocytes. In this study, the expression of potential lineage-specifying factors and/or SMAD4 reduction was introduced in addition to the defined four oncogenes to direct carcinogenesis toward ADC. The cell properties associated with the cell lineage were analyzed in monolayer and organoid cultures and the tumors in mouse xenografts. In the cells expressing Forkhead box A2 (FOXA2), apparent changes in cell properties were observed, such as elevated expression of columnar cell markers and decreased expression of squamous cell markers. Strikingly, the histopathology of tumors expressing FOXA2 resembled cervical ADC, proposing that FOXA2 plays a vital role in dictating the histopathology of cervical cancers.