Zinc transporter 1 functions in copper uptake and cuproptosis.

Copper (Cu) is a co-factor for several essential metabolic enzymes. Disruption of Cu homeostasis results in genetic diseases such as Wilson's disease. Here, we show that the zinc transporter 1 (ZnT1), known to export zinc (Zn) out of the cell, also mediates Cu2+ entry into cells and is required for Cu2+-induced cell death, cuproptosis. Structural analysis and functional characterization indicate that Cu2+ and Zn2+ share the same primary binding site, allowing Zn2+ to compete for Cu2+ uptake. Among ZnT members, ZnT1 harbors a unique inter-subunit disulfide bond that stabilizes the outward-open conformations of both protomers to facilitate efficient Cu2+ transport. Specific knockout of the ZnT1 gene in the intestinal epithelium caused the loss of Lgr5+ stem cells due to Cu deficiency. ZnT1, therefore, functions as a dual Zn2+ and Cu2+ transporter and potentially serves as a target for using Zn2+ in the treatment of Wilson's disease caused by Cu overload.

Tuning the Inter-Metal Interaction between Ni and Fe Atoms in Dual-Atom Catalysts to Boost CO2 Electroreduction.

Dual-atom catalysts (DACs) are promising for applications in electrochemical CO2 reduction due to the enhanced flexibility of the catalytic sites and the synergistic effect between dual atoms. However, precisely controlling the atomic distance and identifying the dual-atom configuration of DACs to optimize the catalytic performance remains a challenge. Here, the Ni and Fe atomic pairs were constructed on nitrogen-doped carbon support in three different configurations: NiFe-isolate, NiFe-N bridge, and NiFe bonding. It was found that the NiFe-N bridge catalyst with NiN4 and FeN4 sharing two N atoms exhibited superior CO2 reduction activity and promising stability when compared to the NiFe-isolate and NiFe-bonding catalysts. A series of characterizations and density functional theory calculations suggested that the N-bridged NiFe sites with an appropriate distance between Ni and Fe atoms can exert a more pronounced synergy. It not only regulated the suitable adsorption strength for the *COOH intermediate but also promoted the desorption of *CO, thus accelerating the CO2 electroreduction to CO. This work provides an important implication for the enhancement of catalysis by the tailoring of the coordination structure of DACs, with the identification of distance effect between neighboring dual atoms.

Auriculasin induces mitochondrial oxidative stress and drives ferroptosis by inhibiting PI3K/Akt pathway in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for the majority of cases of lung cancer with poor outcomes. Auriculasin is a prenylated isoflavone abundant in the root of F. philippinensis with multiple pharmacological effects, including anticancer role. However, its roles in NSCLC remain largely unknown. NSCLC A549 cells were treated with auriculasin in vitro, and used to induce xenograft models. Cell viability was detected via CCK-8 assay. Mitochondrial oxidative stress was analyzed by JC-1 staining, ROS staining, and levels of MDA, SOD and GSH. Ferroptosis was assessed via iron content, and levels of ACSL4, PTGS2, FSP1 and GPX4. The phosphorylation levels of PI3K and Akt were measured by western blot. Auriculasin reduced NSCLC cell viability. Auriculasin promoted mitochondrial oxidative stress by reducing mitochondrial membrane potential, SOD and GSH levels, and enhancing ROS and MDA contents. In addition, auriculasin induced ferroptosis via increasing iron, ACSL4 and PTGS3 levels, and decreasing FSP1 and GPX4 levels. Furthermore, the potential targets of auriculasin in NSCLC were enriched in PI3K/Akt signaling. Auriculasin blunted PI3K/Akt pathway activation by blocking the phosphorylation. Activated PI3K/Akt signaling by activator 740Y-P reversed the effects of auriculasin on mitochondrial oxidative stress and ferroptosis. Finally, auriculasin reduced NSCLC cell growth in xenograft models. Auriculasin facilitates mitochondrial oxidative stress and induces ferroptosis through inhibiting PI3K/Akt pathway in NSCLC.

Construction and Evaluation of BAL-PTX Co-Loaded Lipid Nanosystem for Promoting the Anti-Lung Cancer Efficacy of Paclitaxel and Reducing the Toxicity of Chemotherapeutic Drugs.

Purpose: The present study aimed to develop a lipid nanoplatform, denoted as "BAL-PTX-LN", co-loaded with chiral baicalin derivatives (BAL) and paclitaxel (PTX) to promote the anti-lung cancer efficacy of paclitaxel and reduce the toxicity of chemotherapeutic drugs. Methods: BAL-PTX-LN was optimized through central composite design based on a single-factor experiments. BAL-PTX-LN was evaluated by TEM, particle size, encapsulation efficiency, hemolysis rate, release kinetics and stability. And was evaluated by pharmacokinetics and the antitumor efficacy studied both in vitro and in vivo. The in vivo safety profile of the formulation was assessed using hematoxylin and eosin (HE) staining. Results: BAL-PTX-LN exhibited spherical morphology with a particle size of 134.36 ± 3.18 nm, PDI of 0.24 ± 0.02, and with an encapsulation efficiency exceeding 90%, BAL-PTX-LN remained stable after 180 days storage. In vitro release studies revealed a zero-order kinetic model of PTX from the liposomal formulation. No hemolysis was observed in the preparation group. Pharmacokinetic analysis of PTX in the BAL-PTX-LN group revealed an approximately three-fold higher bioavailability and twice longer t1/2 compared to the bulk drug group. Furthermore, the IC50 of BAL-PTX-LN decreased by 2.35 times (13.48 µg/mL vs 31.722 µg/mL) and the apoptosis rate increased by 1.82 times (29.38% vs 16.13%) at 24 h compared to the PTX group. In tumor-bearing nude mice, the BAL-PTX-LN formulation exhibited a two-fold higher tumor inhibition rate compared to the PTX group (62.83% vs 29.95%), accompanied by a ten-fold decrease in Ki67 expression (4.26% vs 45.88%). Interestingly, HE staining revealed no pathological changes in tissues from the BAL-PTX-LN group, whereas tissues from the PTX group exhibited pathological changes and tumor cell infiltration. Conclusion: BAL-PTX-LN improves the therapeutic effect of poorly soluble chemotherapeutic drugs on lung cancer, which is anticipated to emerge as a viable therapeutic agent for lung cancer in clinical applications.

Recent Advancements and Trends of Topical Drug Delivery Systems in Psoriasis: A Review and Bibliometric Analysis.

Psoriasis is an immune-mediated inflammatory skin disease where topical therapy is crucial. While various dosage forms have enhanced the efficacy of current treatments, their limited permeability and lack of targeted delivery to the dermis and epidermis remain challenges. We reviewed the evolution of topical therapies for psoriasis and conducted a bibliometric analysis from 1993 to 2023 using a predictive linear regression model. This included a comprehensive statistical and visual evaluation of each model's validity, literature profiles, citation patterns, and collaborations, assessing R variance and mean squared error (MSE). Furthermore, we detailed the structural features and penetration pathways of emerging drug delivery systems for topical treatment, such as lipid-based, polymer-based, metallic nanocarriers, and nanocrystals, highlighting their advantages. This systematic overview indicates that future research should focus on developing novel drug delivery systems characterized by enhanced stability, biocompatibility, and drug-carrying capacity.

Survival and analysis of prognostic factors for fibroblastic osteosarcoma patients: a population-based study.

Background: Osteosarcoma is the most common mesenchymal cell malignancy, 10% of which is fibroblastic osteosarcoma (FOS). Due to the low incidence of osteosarcoma, the impact of many pathological factors on survival is still unclear, especially FOS. The goal of this study was to assess the latest survival rates for FOS and the risk factors affecting survival using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Age, sex, race, SEER stage, surgery, radiation, chemotherapy, site of FOS, and survival time were collected from the SEER database for survival and prognostic factor analysis. The patients were randomly assigned to either the training cohort or the testing cohort. The overall survival (OS) curves were obtained by Kaplan-Meier according to different factors. A multivariate Cox regression model and a predictive nomogram have also been constructed. Results: The study enrolled a total of 120 patients. OS at 1, 3, and 5 years for all patients was 90.83%, 79.17%, and 70.83%, respectively. In the 5-year survival analysis, in distant of SEER stage (P<0.01), radiation (P=0.03), and no surgery (P<0.01) were associated with a worse prognosis in patients with FOS. Multivariate analysis showed that age, and in distant of SEER stage were independent indicators of unfavorable prognosis. A nomogram was used to predict the prognosis of FOS and a calibration curve was used to validate the nomogram prediction against the actual observed survival outcomes. Conclusions: In summary, older age, and worse SEER stage were associated with poorer OS. The nomogram effectively predicted the probabilities of 1-, 3-, and 5-year OS, demonstrating strong concordance with the actual observed outcomes.

Boosted Solar Thermochemical Low-temperature CO2 Splitting On Pt/CeO2 By Interface Catalysis.

Solar thermochemical CO2 splitting using metal oxides is considered as a promising approach to produce solar fuels since it is capable to tap abundant sunlight directly and store solar energy in the renewable fuel. It remains a grand challenge to achieve highly efficient CO2 splitting at low temperature (<800 oC) due to insufficient activation of metal oxides for CO2.Herein, the introduction of a small amount of Pt was found to be able to greatly increase the performance of CO2 splitting with the highest peak CO production rate of about 65 mL min-1 g-1, CO productivity of about 53 mL g-1, nearly 100% CO2 conversion and long-term stability for 0.5Pt/CeO2 which exceeded most of the state-of-the-art transition metals-based oxides even at lower temperature (700 oC). This could be attributed to the addition of Pt leading to the formation of an interface (Pt0-Ov-Ce3+) after CH4 reduction, which improved CO2 activation and dissociation due to beneficial breakage of C=O bond by the cooperation of Pt0 and oxygen vacancies in the interface.

Mechanism exploration of synergistic photo-immunotherapy strategy based on a novel exosome-like nanosystem for remodeling the immune microenvironment of HCC.

The immunosuppressive tumor microenvironment (TME) has become a major challenge in cancer immunotherapy, with abundant tumor-associated macrophages (TAMs) playing a key role in promoting tumor immune escape by displaying an immunosuppressive (M2) phenotype. Recently, it was reported that M1 macrophage-derived nanovesicles (M1NVs) can reprogram TAMs to an anti-tumor M1 phenotype, thereby significantly alleviating the immunosuppressive TME and enhancing the anti-tumor efficacy of immunotherapy. Herein, we developed M1NVs loaded with mesoporous dopamine (MPDA) and indocyanine green (ICG), which facilitated the recruitment of M2 TAMs through synergistic photothermal and photodynamic therapy. Thereafter, M1NVs can induce M1 repolarization of TAMs, resulting in increased infiltration of cytotoxic T lymphocytes within the tumor to promote tumor regression. This study investigated the effect of phototherapy on the immune environment of liver cancer using single-cell RNA sequencing (scRNA-seq) by comparing HCC tissues before and after MPDA/ICG@M1NVs + NIR treatment. The results showed significant shifts in cell composition and gene expression, with decreases in epithelial cells, B cells, and macrophages and increases in neutrophils and myeloid cells. Additionally, gene analysis indicated a reduction in pro-inflammatory signals and immunosuppressive functions, along with enhanced B-cell function and anti-tumor immunity, downregulation of the Gtsf1 gene in the epithelial cells of the MPDA/ICG @M1NVs + NIR group, and decreased expression of the lars2 gene in immune subpopulations. Eno3 expression is reduced in M1 macrophages, whereas Clec4a3 expression is downregulated in M2 macrophages. Notably, the B cell population decreased, whereas Pou2f2 expression increased. These genes regulate cell growth, death, metabolism, and tumor environment, indicating their key role in HCC progression. This study highlights the potential for understanding cellular and molecular dynamics to improve immunotherapy.

Rejuvenation Strategy for Inducing and Enhancing Autoimmune Response to Eliminate Senescent Cells.

The process of aging, which involves progressive changes in the body over time, is closely associated with the development of age-related diseases. Cellular senescence is a pivotal hallmark and mechanism of the aging process. The accumulation of senescent cells can significantly contribute to the onset of age-related diseases, thereby compromising overall health. Conversely, the elimination of senescent cells enhances the body's regenerative and reparative capacity, thereby retarding the aging process. Here, we present a brief overview of 12 Hallmarks of aging and subsequently emphasize the potential of immune checkpoint blockade, innate immune cell therapy (including T cells, iNKT cells, macrophages, and NK cells), as well as CAR-T cell therapy for inducing and augmenting immune responses aimed at eliminating senescent cells. In addition to CAR-T cells, we also explore the possibility of engineered immune cells such as CAR-NK and CAR-M cells to eliminate senescent cells. In summary, immunotherapy, as an emerging strategy for the treatment of aging, offers new prospects for age-related research.

Correction: Hybrid 2D perovskite and red emitting carbon dot composite for improved stability and efficiency of LEDs.

Correction for 'Hybrid 2D perovskite and red emitting carbon dot composite for improved stability and efficiency of LEDs' by Amandeep Singh Pannu et al., Nanoscale, 2023, 15, 2659-2666, https://doi.org/10.1039/D2NR06942C.

Epidemiology, incidence, and survival of synovial sarcoma of children: a SEER database analysis.

Background: Roughly 5% to 10% of soft tissue sarcomas fall under the category of synovial sarcomas (SSs), a rare and malignant tumor originating from soft tissues with unclear differentiation, primarily affecting teenagers and young adults. The goal of this study was to assess the latest survival rates for SS of children and the risk factors affecting survival using the Surveillance, Epidemiology and End Results (SEER) database. Methods: Age, sex, race, SEER stage, surgery, radiation, chemotherapy, laterality, site of SS, and survival time were collected in the SEER database for survival and prognostic factor analysis. The overall survival curves and cancer special survival were obtained by Kaplan-Meier according to different factors. A multivariate Cox regression model and a predictive nomogram have also been constructed. Results: A total of 130 patients were enrolled in the study. In the overall survival analysis, age (P=0.01), male (P=0.04), no surgery (P<0.01), chemotherapy (P<0.01), primary tumor site in soft tissue (P=0.02), and in distant of SEER stage (P<0.01) were associated with a worse prognosis in children with SS. Multivariate analysis showed that chemotherapy and in distant of SEER stage were independent indicators of unfavorable prognosis. A similar result was released in the specialized cancer survival analysis. A nomogram was used to predict the prognosis of SS in children and a calibration curve was used to validate the nomogram prediction against the actual observed survival outcomes. Conclusions: In summary, chemotherapy, and worse SEER stage were associated with poorer overall and cancer special survivals. Nomogram was able to predict the probability of 1-, 5- and 10-year overall survivals and showed good consistency with the actual observed outcomes.

Multiprobe Amplification (MPA) with Melting Curve Analysis: A Highly Stable and Cost-Effective Platform for the Simultaneous Detection of Eight Potential Bacterial Bioterrorism Agents in Complex Samples.

We aimed to develop an efficient detection platform that can identify a larger number of suspicious samples in a single test, saving time, manpower, and material costs, and providing vital support to the public health system in coping with the current challenging and dynamic bioterrorism threat landscape, particularly in regions of turmoil and conflict. We have successfully developed a high-throughput, multitarget fluorescent array detection platform by effectively combining integrating multiprobe amplification (MPA) with melting curve analysis. Specifically, we have established reliable laboratory testing methods for eight highly pathogenic bacteria, including Bacillus anthracis, Yersinia pestis, Brucella spp., Burkholderia pseudomallei, Francisella tularensis, Vibrio cholerae, Salmonella typhi, and Staphylococcus aureus. Our method achieves sensitive and specific simultaneous detection of eight target bacteria in one well by optimizing the reaction conditions of MPA. In the assessment of 192 simulated environmental samples, both positive and negative coincidence rates were 100.00%. Among 48 simulated clinical samples, the positive coincidence rate reached 97.73%, while maintaining a perfect negative coincidence rate of 100.00%. Moreover, the detection platform holds immense potential for attaining a more comprehensive bioterrorism screening, and its high cost-effectiveness enables the provision of diverse and adaptable diagnostic methods for public health quarantine in underdeveloped countries and regions.

Adjusting Ion Diffusion Kinetics of Li Deposition Enabled by an Elastic Porous Melamine Sponge Host for Stable Lithium Metal Anodes.

Lithium (Li) dendritic growth and huge volume expansion seriously hamper Li-metal anode development. Herein, we design a lightweight 3D Li-ion-affinity host enabled by silver (Ag) nanoparticles fully decorating a porous melamine sponge (Ag@PMS) for dendrite-free and high-areal-capacity Li anodes. The compact Ag nanoparticles provide abundant preferred nucleation sites and give the host strong conductivity. Moreover, the high specific surface area and polar groups of the elastic, porous melamine sponge enhance the Li-ion diffusion kinetics, prompting homogeneity of Li deposition and stripping. As expected, the integrated 3D Ag@PMS-Li anode delivered a remarkable electrochemical performance, with a Coulombic efficiency (CE) of 97.14% after 450 cycles at 1 mA cm-2. The symmetric cell showed an ultralong lifespan of 3400 h at 1 mA cm-2 for 1 mAh cm-2. This study provides a facile and cost-effective strategy to design an advanced 3D framework for the preparation of a stable dendrite-free Li metal anode.

The effects of nitric oxide in Alzheimer's disease.

Alzheimer's disease (AD), the most prevalent cause of dementia, is a progressive neurodegenerative condition that commences subtly and inexorably worsens over time. Despite considerable research, a specific drug that can fully cure or effectively halt the progression of AD remains elusive. Nitric oxide (NO), a crucial signaling molecule in the nervous system, is intimately associated with hallmark pathological changes in AD, such as amyloid-beta deposition and tau phosphorylation. Several therapeutic strategies for AD operate through the nitric oxide synthase/NO system. However, the potential neurotoxicity of NO introduces an element of controversy regarding its therapeutic utility in AD. This review focuses on research findings concerning NO's role in experimental AD and its underlying mechanisms. Furthermore, we have proposed directions for future research based on our current comprehension of this critical area.

Research on the Mechanism and Material Basis of Corn (Zea mays L.) Waste Regulating Dyslipidemia.

Corn (Zea mays L.) is an essential gramineous food crop. Traditionally, corn wastes have primarily been used in feed, harmless processing, and industrial applications. Except for corn silk, these wastes have had limited medicinal uses. However, in recent years, scholars have increasingly studied the medicinal value of corn wastes, including corn silk, bracts, husks, stalks, leaves, and cobs. Hyperlipidemia, characterized by abnormal lipid and/or lipoprotein levels in the blood, is the most common form of dyslipidemia today. It is a significant risk factor for atherosclerosis and can lead to cardiovascular and cerebrovascular diseases if severe. According to the authors' literature survey, corn wastes play a promising role in regulating glucose and lipid metabolism. This article reviews the mechanisms and material basis of six different corn wastes in regulating dyslipidemia, aiming to provide a foundation for the research and development of these substances.

Detection and phylogenetic classification of Neoehrlichia mikurensis in rodents from the region of Liupan Mountain, China.

Neoehrlichia mikurensis (N. mikurensis) is an emerging tick-borne pathogen that can cause neoehrlichiosis. Rodents are considered the major host for N. mikurensis. Currently, N. mikurensis has been detected in rodents in several studies from China and other countries. However, no research on N. mikurensis infection in rodents has been reported in the Liupan mountain region. The region of Liupan Mountain, located in northwestern China, is the center of the triangle formed by the cities of Xi'an, Yinchuan, and Lanzhou, with multiple tourist sites in the region. To survey whether there is N. mikurensis in hosts, rodents were captured in this region in September 2020. A nested polymerase chain reaction was used to detect the DNA of N. mikurensis, followed by nucleotide sequencing and phylogenetic analysis. In the region, among 88 rodents, 3 rodents were detected positive for N. mikurensis, a detection rate of 3.4%. Based on phylogenetic analysis of the partial groEL gene sequences, N. mikurensis from rodents in Liupan Mountain clustered in the same evolutionary branch with those found in rodents from Japan, Russia, and northeastern China, and also in ticks and clinical cases from Heilongjiang Province in northeastern China.

Predictive value of the C-reactive protein to albumin ratio in the treatment of septic arthritis in young children: A retrospective study.

INTRODUCTION: Septic arthritis (SA) can cause lifelong disability in children due to joint dysfunction but there is controversy regarding the timing of surgery in SA. The C-reactive protein to albumin ratio (CAR) has emerged as a novel marker of inflammation and has been extensively used in predicting inflammatory bowel disease, arthritis, and systemic inflammation. Despite advancements, few studies have evaluated the role of CAR in SA. Therefore, the present study was aimed to investigate whether CAR could serve as predictive indicators for determining whether patients under four years old with SA should be managed conservatively or require surgical intervention, and to analyze its predictive accuracy. HYPOTHESIS: An increase in CAR values among patients under four years old with SA indicates the requirement of surgical intervention. MATERIALS AND METHODS: This retrospective study enrolled SA children under four years old and divided them into two groups, the surgery and conservative groups. The clinical data between the two groups were compared and multivariate logistic regression was performed to assess the independent predictors of SA requiring surgery. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to determine the predictive ability of CAR in SA requiring surgery. RESULTS: A total of 82 SA children were included, with 42 children (51.3%) in the surgery group and 40 children (48.7%) in the conservative group. CAR ≥ 1.165 [OR = 12.641, 95% CI (4.264 - 37.479),p < 0.001] was an independent predictive indicator for surgery in SA children under four years old, with a predicted sensitivity of 0.714, specificity of 0.850, and AUC of 0.793 [95% (0.694-0.893)] indicating good predictive accuracy. DISCUSSION: CAR to be an independent predictive indicator patients under four years old with SA. And a CAR value ≥ 1.165 upon admission in these patients suggests the necessity for surgical intervention. LEVEL OF EVIDENCE: IV, Retrospective study.

Short-term forecasting of vegetable prices based on LSTM model-Evidence from Beijing's vegetable data.

The vegetable sector is a vital pillar of society and an indispensable part of the national economic structure. As a significant segment of the agricultural market, accurately forecasting vegetable prices holds significant importance. Vegetable market pricing is subject to a myriad of complex influences, resulting in nonlinear patterns that conventional time series methodologies often struggle to decode. In this paper, we exploit the average daily price data of six distinct types of vegetables sourced from seven key wholesale markets in Beijing, spanning from 2009 to 2023. Upon training an LSTM model, we discovered that it exhibited exceptional performance on the test dataset. Demonstrating robust predictive performance across various vegetable categories, the LSTM model shows commendable generalization abilities. Moreover, LSTM model has a higher accuracy compared to several machine learning methods, including CNN-based time series forecasting approaches. With R2 score of 0.958 and MAE of 0.143, our LSTM model registers an enhancement of over 5% in forecast accuracy relative to conventional machine learning counterparts. Therefore, by predicting vegetable prices for the upcoming week, we envision this LSTM model application in real-world settings to aid growers, consumers, and policymakers in facilitating informed decision-making. The insights derived from this forecasting research could augment market transparency and optimize supply chain management. Furthermore, it contributes to the market stability and the balance of supply and demand, offering a valuable reference for the sustainable development of the vegetable industry.

Strategy to Antibacterial, High-Mechanical, and Degradable Polylactic Acid/Chitosan Composite Film through Reactive Compatibilization via Epoxy Chain Extender.

Research into the production of antibacterial, high strength, and environmentally friendly biobased films for use in food packaging is crucial due to growing concerns about food safety. Herein, the preparation of antibacterial, high mechanical, and degradable Polylactic acid/chitosan (PLA/CS) composite films with exceptional interfacial compatibility through reactive compatibilization via the epoxy chain extender ADR4468 is reported. A strong bond, in the form of a chemical bond between PLA and CS, is established by the cycloaddition opening reaction of ADR, which induces cross-linking between hydroxyl and carboxyl groups on the molecular chains. As a result, the elongation at break increased by 31.8% compared to the composite film without ADR. In addition, the composite films exhibited good compost degradability, with a mass reduction of 42-45% after 100 days of degradation.