Cotransport of nanoplastics with nZnO in saturated porous media: From brackish water to seawater.

The ocean serves as a repository for various types of artificial nanoparticles. Nanoplastics (NPs) and nano zinc oxide (nZnO), which are frequently employed in personal care products and food packaging materials, are likely simultaneously released and eventually into the ocean with surface runoff. Therefore, their mutual influence and shared destiny in marine environment cannot be ignored. This study examined how nanomaterials interacted and transported through sea sand in various salinity conditions. Results showed that NPs remained dispersed in brine, while nZnO formed homoaggregates. In seawater of 35 practical salinity units (PSU), nZnO formed heteroaggregates with NPs, inhibiting NPs mobility and decreasing the recovered mass percentage (Meff) from 24.52% to 12.65%. In 3.5 PSU brackish water, nZnO did not significantly aggregate with NPs, and thus barely affected their mobility. However, NPs greatly enhanced nZnO transport with Meff increasing from 14.20% to 25.08%, attributed to the carrier effect of higher mobility NPs. Cotransport from brackish water to seawater was simulated in salinity change experiments and revealed a critical salinity threshold of 10.4 PSU, below which the mobility of NPs was not affected by coexisting nZnO and above which nZnO strongly inhibited NP transport. This study highlights the importance of considering the mutual influence and shared destiny of artificial nanoparticles in the marine environment and how their interaction and cotransport are dependent on changes in seawater salinity.

Nomograms for prognosis prediction in esophageal adenocarcinoma: realities and challenges.

Prognostic assessment is of great significance for individualized treatment and care of cancer patients. Although the TNM staging system is widely used as the primary prognostic classifier for solid tumors in clinical practice, the complexity of tumor occurrence and development requires more personalized probability prediction models than an ordered staging system. By integrating clinical, pathological, and molecular factors into digital models through LASSO and Cox regression, a nomogram could provide more accurate personalized survival estimates, helping clinicians and patients develop more appropriate treatment and care plans. Esophageal adenocarcinoma (EAC) is a common pathological subtype of esophageal cancer with poor prognosis. Here, we screened and comprehensively reviewed the studies on EAC nomograms for prognostic prediction, focusing on performance evaluation and potential prognostic factors affecting survival. By analyzing the strengths and limitations of the existing nomograms, this study aims to provide assistance in constructing high-quality prognostic models for EAC patients.

Different inhibitory mechanisms of flexible and rigid clay minerals on the transport of microplastics in marine porous media.

Colloidal interactions between clay minerals and microplastics (MPs) in high salinity seawater are crucial for determining MP fate in marine environments. Montmorillonite (MMT) forms thin and pliable films that tightly cover MPs, while the thick and rigid lamellae of kaolinite (KLT) have limited contact with MPs, resulting in unstable bonding. However, a small quantity of small-sized KLT can create relatively stable heteroaggregates by embedding into the interstitial spaces of MPs. Both MMT and KLT colloids can decrease the mobility of MPs in seawater-saturated sea sand, but their breakthrough curves (BTCs) show distinct phenomena of "blocking" and "ripening", respectively. The "blocking" phenomenon occurs when flexible MMT adheres to the sand surface, depleting attachment sites quickly and inhibiting the retention of subsequent heteroaggregates of MMT-wrapped MPs. The transport of single MMT also experiences colloid competition for attachment sites, but pre-equilibration experiments reveal no competition between MMT and bare MPs for attachment sites. Instead, the attached MMT provides additional attachment sites for MPs. These results suggest that the wrapping of MPs by MMT plays a dominant role in the "blocking" of cotransport. In contrast, rigid KLT forms a three-dimensional stack on the sand surface, offering more attachment sites for subsequent MPs and heteroaggregates.

TROP2 is highly expressed in triple-negative breast cancer CTCs and is a potential marker for epithelial mesenchymal CTCs.

Circulating tumor cells (CTCs) are the seeds of distant metastases of malignant tumors and are associated with malignancy and risk of metastasis. However, tumor cells undergo epithelial-mesenchymal transition (EMT) during metastasis, leading to the emergence of different types of CTCs. Real-time dynamic molecular and functional typing of CTCs is necessary to precisely guide personalized treatment. Most CTC detection systems are based on epithelial markers that may fail to detect EMT CTCs. Therefore, it is clinically important to identify new markers of different CTC types. In this study, bioinformatics analysis and experimental assays showed that trophoblast cell surface antigen 2 (TROP2), a target molecule for advanced palliative treatment of triple-negative breast cancer (TNBC), was highly expressed in TNBC tissues and tumor cells. Furthermore, TROP2 can promote the migration and invasion of TNBC cells by upregulating EMT markers. The specificity and potential of TROP2 as an EMT-associated marker of TNBC CTCs were evaluated by flow cytometry, immunofluorescence, spiking experiments, and a well-established CTC assay. The results indicated that TROP2 is a potential novel CTC marker associated with EMT, providing a basis for more efficacious markers that encompass CTC heterogeneity in patients with TNBC.

Constructing Asymmetric Charge Polarized NiCo Prussian Blue Analogue for Promoted Electrocatalytic Methanol to Formate Conversion.

The highly selective electrochemical conversion of methanol to formate is of great significance for various clean energy devices, but understanding the structure-to-property relationship remains unclear. Here, the asymmetric charge polarized NiCo prussian blue analogue (NiCo PBA-100) is reported to exhibit remarkable catalytic performance with high current density (210 mA cm-2 @1.65 V vs RHE) and Faraday efficiency (over 90%). Meanwhile, the hybrid water splitting and Zinc-methanol-battery assembled by NiCo PBA-100 display the promoted performance with decent stability. X-ray absorption spectroscopy (XAS) and operando Raman spectroscopy indicate that the asymmetric charge polarization in NiCo PBA leads to more unoccupied states of Ni and occupied states of Co, thereby facilitating the rapid transformation of the high-active catalytic centers. Density functional theory calculations combining operando Fourier transform infrared spectroscopy demonstrate that the final reconstructed catalyst derived by NiCo PBA-100 exhibits rearranged d band properties along with a lowered energy barrier of the rate-determining step and favors the desired formate production.

Relict Plants Are Better Able to Adapt to Climate Change: Evidence from Desert Shrub Communities.

Shrubs are the main dominant plants in arid desert systems and play an important role in maintaining the biodiversity, ecosystem services and stability of desert ecosystems. Studies have shown that the survival of a large number of shrub species in desert areas under the influence of climate change is significantly threatened, with different species showing different response strategies. To test the tolerance of different shrub species to climate change, this study selected 10 dominant shrub species (ancient relict shrub species and regional endemic shrub species) in the Alashan desert area as the research object. Based on a field survey of species distribution, a species distribution model was developed to simulate the suitable distribution area of shrub species under current conditions and under future climate change scenarios. The distribution changes of ancient relict and regional endemic shrub species under the climate change scenarios were tested, and the tolerance of the two types of shrub to climate change was analyzed. The results showed that under different climate change scenarios, except for Ammopiptanthus mongolicus, the total suitable area of four out of the five relict plants was relatively stable, the potential distribution area of Tetraena mongolica increased, and the future distribution pattern was basically consistent with the current distribution. However, the suitable area of typical desert plants was unstable under different climate change scenarios. Except for Kalidium foliatum, the suitable distribution areas of four out of the five shrubs showed different degrees of reduction, and the distribution location showed significant migration. Based on the research results, climate change will lead to the reduction and displacement of the distribution area of typical desert shrubs, while relict shrubs will be less affected by climate change. This is because, compared to desert species, relict plants have a longer evolutionary history and have developed a wider range of adaptations after experiencing dramatic environmental changes. This study provides a scientific basis for actively responding to the impacts of climate change on desert ecosystems.

RNF13 protects against pathological cardiac hypertrophy through p62-NRF2 pathway.

Heart failure (HF) severely impairs human health because of its high incidence and mortality. Cardiac hypertrophy is the main cause of HF, while its underlying mechanism is not fully clear. As an E3 ubiquitin ligase, Ring finger protein 13 (RNF13) plays a crucial role in many disorders, such as liver immune, neurological disease and tumorigenesis, whereas the function of RNF13 in cardiac hypertrophy remains largely unknown. In the present study, we found that the protein expression of RNF13 is up-regulated in the transverse aortic constriction (TAC)-induced murine hypertrophic hearts and phenylephrine (PE)-induced cardiomyocyte hypertrophy. Functional investigations indicated that RNF13 global knockout mice accelerates the degree of TAC-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis and heart dysfunction. On the contrary, adeno-associated virus 9 (AAV9) mediated-RNF13 overexpression mice alleviated cardiac hypertrophy. Furthermore, we demonstrated that adenoviral RNF13 attenuates the PE-induced cardiomyocyte hypertrophy and down-regulates the expression of cardiac hypertrophic markers, while the opposite results were observed in the RNF13 knockdown group. The RNA-sequence of RNF13 knockout and wild type mice showed that RNF13 deficiency activates oxidative stress after TAC surgery. In terms of the mechanism, we found that RNF13 directly interacted with p62 and promoted the activation of downstream NRF2/HO-1 signaling. Finally, we proved that p62 knockdown can reverse the effect of RNF13 in cardiac hypertrophy. In conclusion, RNF13 protects against the cardiac hypertrophy via p62-NRF2 axis.

LncRNA DGCR5-encoded polypeptide RIP aggravates SONFH by repressing nuclear localization of ß-catenin in BMSCs.

The differentiation fate of bone marrow mesenchymal stem cells (BMSCs) affects the progression of steroid-induced osteonecrosis of the femoral head (SONFH). We find that lncRNA DGCR5 encodes a 102-amino acid polypeptide, RIP (Rac1 inactivated peptide), which promotes the adipogenic differentiation of BMSCs and aggravates the progression of SONFH. RIP, instead of lncRNA DGCR5, binds to the N-terminal motif of RAC1, and inactivates the RAC1/PAK1 cascade, resulting in decreased Ser675 phosphorylation of ß-catenin. Ultimately, the nuclear localization of ß-catenin decreases, and the differentiation balance of BMSCs tilts toward the adipogenesis lineage. In the femoral head of rats, overexpression of RIP causes trabecular bone disorder and adipocyte accumulation, which can be rescued by overexpressing RAC1. This finding expands the regulatory role of lncRNAs in BMSCs and suggests RIP as a potential therapeutic target.

Genetic lineage tracing in skin reveals predominant expression of HEY2 in dermal papilla during telogen and that HEY2+ cells contribute to the regeneration of dermal cells during wound healing.

Dermal papilla (DP) cells are specialized mesenchymal cells that play a crucial role in regulating hair morphology, colour and growth through the secretion of specific factors. It is still unclear what the source of progenitor cells is for dermal cell regeneration during wound healing, and whether DP cells are involved in this process. We analyzed the gene expression profile of various skin cell populations using existing datasets and found that the Hey2 gene was predominantly expressed in DP cells. We introduced Hey2-CreERT2 knockin mice and crossed them with Rosa26-ZsGreen reporter mice. After induction in the double transgenic mice by administration of tamoxifen, the reporter ZsGreen was found to be predominantly expressed in DP cells both at anagen and telogen phases, and broadly expressed in some other dermal cells at anagen. We also created a wound after tamoxifen induction, and found there were abundant ZsGreen+ cells in the regenerated dermis. We conclude that the HEY2+ DP cells and dermal cells exhibit some stemness properties and can contribute to the dermal cell regeneration during wound healing.

Sensitive Quantitative In Vivo Assay for Evaluating the Effects of Biomolecules on Hair Growth and Coloring Using Direct Microinjections into Mouse Whisker Follicles.

Many people suffer from hair loss and abnormal skin pigmentation, highlighting the need for simple assays to support drug discovery research. Current assays have various limitations, such as being in vitro only, not sensitive enough, or unquantifiable. We took advantage of the bilateral symmetry and large size of mouse whisker follicles to develop a novel in vivo assay called "whisker follicle microinjection assay". In this assay, we plucked mouse whiskers and then injected molecules directly into one side of the whisker follicles using microneedles that were a similar size to the whiskers, and we injected solvent on the other side as a control. Once the whiskers grew out again, we quantitatively measured their length and color intensity to evaluate the effects of the molecules on hair growth and coloring. Several chemicals and proteins were used to test this assay. The chemicals minoxidil and ruxolitinib, as well as the protein RSPO1, promoted hair growth. The effect of the clinical drug minoxidil could be detected at a concentration as low as 0.001%. The chemical deoxyarbutin inhibited melanin production. The protein Nbl1 was identified as a novel hair-growth inhibitor. In conclusion, we successfully established a sensitive and quantitative in vivo assay to evaluate the effects of chemicals and proteins on hair growth and coloring and identified a novel regulator by using this assay. This whisker follicle microinjection assay will be useful when investigating protein functions and when developing drugs to treat hair loss and abnormal skin pigmentation.

Th17/Treg balance is regulated by myeloid-derived suppressor cells in experimental autoimmune myocarditis.

OBJECTIVE: Autoimmune myocarditis is caused by both innate and adaptive immune responses. Many studies have found that myeloid-derived suppressor cells (MDSCs) suppress T-cell responses and reduce immune tolerance, while MDSCs may serve as a key player in inflammatory responses and pathogenesis in variety of autoimmune diseases. However, research into the role of MDSCs in experimental autoimmune myocarditis (EAM) remains lacking. METHODS AND RESULTS: We discovered that the expansion of MDSCs in EAM was closely related to the severity of myocardial inflammation. At an early stage of EAM, both adoptive transfer (AT) and selective depletion of MDSCs could inhibit the expression of IL-17 in CD4+ cells and downregulate the Th17/Treg ratio, alleviating excessive inflammation of EAM myocarditis. In another experiment, in addition, MDSCs transferred after selective depletion could increase IL-17 and Foxp3 expressions in CD4+ cells, as well as the Th17/Treg ratio, contributing to the aggravation of myocardial inflammation. MDSCs promoted the Th17 cell induction under Th17-polarizing conditions in vitro but suppressed Treg expansion. CONCLUSION: These findings suggest that MDSCs play a plastic role in sustaining mild inflammation in EAM by shifting Th17/Treg balance.

Optimization Methods of Tungsten Oxide-Based Nanostructures as Electrocatalysts for Water Splitting.

Electrocatalytic water splitting, as a sustainable, pollution-free and convenient method of hydrogen production, has attracted the attention of researchers. However, due to the high reaction barrier and slow four-electron transfer process, it is necessary to develop and design efficient electrocatalysts to promote electron transfer and improve reaction kinetics. Tungsten oxide-based nanomaterials have received extensive attention due to their great potential in energy-related and environmental catalysis. To maximize the catalytic efficiency of catalysts in practical applications, it is essential to further understand the structure-property relationship of tungsten oxide-based nanomaterials by controlling the surface/interface structure. In this review, recent methods to enhance the catalytic activities of tungsten oxide-based nanomaterials are reviewed, which are classified into four strategies: morphology regulation, phase control, defect engineering, and heterostructure construction. The structure-property relationship of tungsten oxide-based nanomaterials affected by various strategies is discussed with examples. Finally, the development prospects and challenges in tungsten oxide-based nanomaterials are discussed in the conclusion. We believe that this review provides guidance for researchers to develop more promising electrocatalysts for water splitting.

GNPNAT1 is a potential biomarker correlated with immune infiltration and immunotherapy outcome in breast cancer.

Background: Glucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a crucial enzyme involving hexosamine biosynthesis pathway and is upregulated in breast cancer (BRCA). However, its biological function and mechanism on patients in BRCA have not been investigated. Methods: In this study, the differential expression of GNPNAT1 was analyzed between BRCA tissues and normal breast tissues using the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, which was validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry. Then, the potential clinical value of GNPNAT1 in BRCA was investigated based on TCGA database. Functional enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Variation Analysis, were performed to explore the potential signaling pathways and biological functions involved in GNPNAT1 in BRCA. Tumor immune infiltration was analyzed using ESTIMATE, CIBERSORT and TISIDB database; and immune therapy response scores were assessed using TIDE. Finally, Western blot, Cell counting kit-8 and Transwell assay were used to determine the proliferation and invasion abilities of breast cancer cells with GNPNAT1 knockdown. Results: GNPNAT1 was up-regulated in BRCA tissues compared with normal tissues which was subsequently verified in different cell lines and clinical tissue samples. Based on TCGA and GEO, the overexpression of GNPNAT1 in BRCA contributed to a significant decline in overall survive and disease specific survive. Functional enrichment analyses indicated that the enriched pathways in high GNPNAT1 expression group included citrate cycle, N-glycan biosynthesis, DNA repair, and basal transcription factors. Moreover, the overexpression of GNPNAT1 was negatively correlated with immunotherapy response and the levels of immune cell infiltration of CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. Knockdown of GNPNAT1 impairs the proliferation and invasion abilities of breast cancer cells. Conclusion: GNPNAT1 is a potential diagnostic, prognostic biomarker and novel target for intervention in BRCA.

PDK1-stabilized LncRNA SPRY4-IT1 promotes breast cancer progression via activating NF-κB signaling pathway.

Pyruvate dehydrogenase kinase 1 (PDK1) is a widely known glycolytic enzyme, and some evidence showed that PDK1 promoted breast cancer by multiple approaches. However, very few lncRNAs have been identified to be associated with PDK1 in breast cancer in previous research. In this study, we found that lncRNA sprouty4-intron transcript 1 (SPRY4-IT1) was regulated by PDK1 with correlation analysis, and PDK1 upregulated SPRY4-IT1 remarkably in breast cancer cells, as PDK1 interacted with SPRY4-IT1 in the nucleus and significantly enhanced the stability of SRPY4-IT1. Furthermore, SPRY4-IT1 was highly expressed in breast cancer, significantly promoted the proliferation and inhibited apoptosis of breast cancer cells. In terms of mechanism, SPRY4-IT1 inhibited the transcription of NFKBIA and the expression of IκBα, thus promoting the formation of p50/p65 complex and activating NF-κB signaling pathway, which facilitated survival of breast cancer cells. Therefore, our finding reveals that PDK1/SPRY4-IT1/NFKBIA axis plays a crucial role that promoting tumor progression, and SPRY4-IT1 knockdown incombined with PDK1 inhibitor is promising to be a new therapeutic strategy in breast cancer.

Application of iontophoresis in ophthalmic practice: an innovative strategy to deliver drugs into the eye.

Delivery of drugs to special locations of ocular lesions, while minimizing systemic and local toxic effects, is recognized as a critical challenge in the ophthalmic practice. The special anatomy and physiology barriers within the eyeball entail effective drug delivery systems. Emerging attempts in drug delivery has led to developments in ocular iontophoresis, which acts as a noninvasive technology to enhance drug penetration using a small electric current. This technique offers greater flexibility to deliver desired drug dose in a controlled and tolerable manner. In previous studies, this technique has been testified to deliver antibiotics, corticoid, proteins and other gene drugs into the eye with the potency of treating or alleviating diverse ophthalmological diseases including uveitis, cataract, retinoblastoma, herpes simplex and cytomegalovirus retinitis (CMVR), etc. In this review, we will introduce the recent developments in iontophoresis device. We also summarize the latest progress in coulomb controlled iontophoresis (CCI), hydrogel ionic circuit (HIC) and EyeGate II delivery system (EGDS), as well as overview the potential toxicity of iontophoresis. We will discuss these factors that affect the efficacy of iontophoresis experiments, and focus on the latest progress in its clinical application in the treatment of eye diseases.

The application and progression of CRISPR/Cas9 technology in ophthalmological diseases.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (Cas) system is an adaptive immune defence system that has gradually evolved in bacteria and archaea to combat invading viruses and exogenous DNA. Advances in technology have enabled researchers to enhance their understanding of the immune process in vivo and its potential for use in genome editing. Thus far, applications of CRISPR/Cas9 genome editing technology in ophthalmology have included gene therapy for corneal dystrophy, glaucoma, congenital cataract, Leber's congenital amaurosis, retinitis pigmentosa, Usher syndrome, fundus neovascular disease, proliferative vitreoretinopathy, retinoblastoma and other eye diseases. Additionally, the combination of CRISPR/Cas9 genome editing technology with adeno-associated virus vector and inducible pluripotent stem cells provides further therapeutic avenues for the treatment of eye diseases. Nonetheless, many challenges remain in the development of clinically feasible retinal genome editing therapy. This review discusses the development, as well as mechanism of CRISPR/Cas9 and its applications and challenges in gene therapy for eye diseases.

Efficient Synthesis and Evaluation of Novel Sulfonated Dihydropyrimidinthione Derivatives for the Treatment of UV-B-Induced Corneal Damage.

UV-B-induced corneal damage remains a challenge in clinics, and it is needed to develop novel and effective medicines against UV-B induced photodamage. 3,4-Dihydropyrimidine-2(1H)-thione derivatives have shown many interesting biological activities, including antibacterial, anti-inflammatory, antioxidant, etc. In order to find a promising anticorneal photodamage agent, we designed and synthesized two novel sulfonated dihydropyrimidinthione derivatives to evaluate cytoprotective effect against UV-B-mediated photodamage. With simple structure, compound 6 possessed good water solubility, photostability and biocompatibility. We demonstrated that 6 exhibited significant cytoprotective effects against UV-B-mediated photodamage and the cell viability was up to 93% at 0.2 mg mL-1 . The corneal cells were highly sensitive to UV-B radiation, resulting in the release of inflammatory mediators and DNA damage, which were significantly reversed by 6. Moreover, compound 6 reduced Bax and cleaved Caspase-3 expressions to suppress UV-B mediated the intrinsic apoptosis pathway. Our findings suggest that 6 is a promising UV-B resistant agent with potential to be a promising drug candidate for the treatment of corneal photodamage.

Corrigendum: Identification of differentially expressed hub genes associated with immune cell recruitment in claudin-low breast cancer.

[This corrects the article DOI: 10.3389/fonc.2022.848206.].

Correlation of Serum M-CSF, CER, and TIMP-1 Levels with Liver Fibrosis in Viral Hepatitis.

Objective: This research is aimed at investigating the relationship between liver fibrosis in viral hepatitis and macrophage colony-stimulating factor (M-CSF), tissue inhibitor of matrix metalloproteinase (TIMP-1), and ceruloplasmin (CER) in serum level. Methods: Patients were randomly selected among those admitted to our hospital, and 60 healthy volunteers were chosen to serve as control participants. The levels of serum M-CSF, CER, and TIMP-1 were compared. According to the severity of their liver fibrosis, patients with CHB were separated into four groups: S1, S2, S3, and S4. Serum levels of M-CSF, CER, and TIMP-1 were correlated with liver fibrosis and hepatitis markers, and the diagnostic usefulness of the three indices was assessed with liver cirrhosis patients. Results: Increases in M-CSF and TIMP-1 in the CHB group but decreases in CER were statistically significant (P < 0.05). Serum levels of M-CSF, CER, TIMP-1, HA, PC-III, C-IV, and LN differed significantly across the four study groups (P < 0.05). Over time, as liver fibrosis worsened, we observed a progressive uptick in M-CSF, TIMP-1, LN, HA, C-IV, and PC-III levels and a progressive downtick in CER levels, with significant (P < 0.05) differences between the groups. There was a significant positive correlation between liver fibrosis and serum M-CSF, PC-III, TIMP-1, HA, LN, and C-IV levels in the CHB group (P < 0.05) and a significant negative correlation between serum CER and these same factors (P < 0.05). The AUC of 0.956 for diagnosing the S4 stage was greater than that of 0.857, 0.851, and 0.817 for M-CSF, CER, and TIMP-1, respectively. Conclusions: In CHB patients, the liver fibrosis degree is associated with the M-CSF, CER, and TIMP-1 levels, and the combined clinical detection of these three markers has better diagnostic significance.