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Abstract Optical skyrmions are an emerging class of structured light with sophisticated particle-like topologies with great potential for revolutionizing modern informatics. However, the current generation of optical skyrmions involves complex or bulky systems, hindering the development of practical applications. Here, exploiting the emergent “lab-on-fiber” technology, we demonstrate the design of a metafiber-integrated photonic skyrmion generator. We not only successfully generate high-quality optical skyrmions from metafibers, but also verify their remarkable properties, such as topology switchability and topology stability with subwavelength polarization features beyond the diffraction limits. Our flexible fiber-integrated optical skyrmions platform paves the avenue for future applications of topologically-enhanced remote super-resolution microscopy and robust information transfer.

Abstract Background The safety and efficacy of combination of gefitinib with chemotherapy and bevacizumab in treatment patients with epidermal growth factor receptor (EGFR) mutations are currently unknown. This study was designed to evaluate the safety and preliminary efficacy of a combination therapy consisting of gefitinib, bevacizumab, pemetrexed, and carboplatin in patients with advanced non-squamous non–small cell lung cancer (NSCLC) harboring EGFR mutations. Methods Eligible patients with EGFR-mutated advanced non-squamous NSCLC were recruited and received gefitinib combination with bevacizumab plus pemetrexed and carboplatin treatment. The primary endpoints were safety and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS). Results From June 2019 to June 2021, 20 patients were enrolled in this study. The median follow-up was 33.8 months (95% CI, 31.0-36.6). Grade ≥ 3 adverse events was 65%, including neutropenia (30%), thrombocytopenia (20%), nausea (20%), skin rash (20%), bleeding (10%), and increased ALT (10%). There was no death related to toxicity occurred. The median PFS was 28 months (95% CI, 20.4–35.6). the ORR was 95% (95% CI, 75.1-99.9%), the DCR was 100% (95% CI, 83.2-100%), and the median DOR was 26.4 months (95% CI, 18.9–33.9). The median OS has not been reached. Conclusion The results of this study demonstrate that the four-drug combination regimen, led by gefitinib, is manageable and tolerated and effective for patients with EGFR-mutated advanced non-squamous NSCLC.

To study the quality discrepancy of jujube vinegar brewed from different jujube varieties, six types of jujube vinegar made from different varieties of jujube were evaluated by the analysis of basic physicochemical components (such as pH, total acid, total phenol and total flavone), color, in vitro functional activity (antioxidant capacity and lipid-lowering ability), organic acids, amino acids, and volatile aroma components, combined with electronic nose and sensory evaluation. The results showed that there were significant differences in the quality of jujube vinegar brewed from different jujubes. In terms of physical and chemical analysis, the total acid and total flavonoids of Xinjiang jujube vinegar were the highest, which were 54.87 g/L and 1168.84 mg RE/L, respectively. By contrast, the total phenolic content of Xinjiang Jun-jujube jujube vinegar was the highest, which was 1815.63 mg GAE/L. Henan Lingbao jujube vinegar and Fuping jujube vinegar had better color values. Xinjiang Jujube vinegar showed the best antioxidant and lipid lowering activities. Fuping jujube vinegar had the lowest total organic acid content of 47.07 g/L. Xinjiang gray jujube vinegar and Xinjiang Jun-jujube vinegar had higher essential amino acid and total amino acid content, while Hebei Fuping jujube vinegar had lower amino acid content. A total of 41 volatile aromas were detected in 6 kinds of jujube vinegar, and there were certain differences in the types and contents of volatile aromas contained in different kinds of jujube vinegar. The sensory evaluation showed that all jujubes were suitable for brewing jujube vinegar, among which Xinjiang Hui-jujube vinegar had the best sensory acceptance. In summary, there were certain differences in the quality of 6 kinds of jujube vinegar. The high functional activity of Xinjiang Jun-jujube vinegar made it more suitable as a functional fruit vinegar. Based on the high sensory acceptance of Xinjiang Hui-jujube vinegar, the Xinjiang Hui-jujube would be suitable for the vinegar processing too.

Abstract AlphaFold model has reshaped biological research. However, vast unstructured data in the entire AlphaFold field requires further analysis to fully understand the current research landscape and guide future exploration. Thus, this scientometric analysis aimed to identify critical research clusters, track emerging trends, and highlight underexplored areas in this field by utilizing machine-learning-driven informatics methods. Quantitative statistical analysis reveals that the AlphaFold field is enjoying an astonishing development trend (Annual Growth Rate = 180.13%) and global collaboration (International Co-authorship = 33.33%). Unsupervised clustering algorithm, time series tracking, and global impact assessment point out that Cluster 3 (Artificial Intelligence-Powered Advancements in AlphaFold for Structural Biology) has the greatest influence (Average Citation = 48.36 ± 184.98). Additionally, regression curve and hotspot burst analysis highlight “structure prediction” (s = 12.40, R2 = 0.9480, p = 0.0051), “artificial intelligence” (s = 5.00, R2 = 0.8096, p = 0.0375), “drug discovery” (s = 1.90, R2 = 0.7987, p = 0.0409), and “molecular dynamics” (s = 2.40, R2 = 0.8000, p = 0.0405) as core hotspots driving the research frontier. More importantly, the Walktrap algorithm further reveals that “structure prediction, artificial intelligence, molecular dynamics” (Relevance Percentage[RP] = 100%, Development Percentage[DP] = 25.0%), “sars-cov-2, covid-19, vaccine design” (RP = 97.8%, DP = 37.5%), and “homology modeling, virtual screening, membrane protein” (RP = 89.9%, DP = 26.1%) are closely intertwined with the AlphaFold model but remain underexplored, which implies a broad exploration space. In conclusion, through the machine-learning-driven informatics methods, this scientometric analysis offers an objective and comprehensive overview of global AlphaFold research, identifying critical research clusters and hotspots while prospectively pointing out underexplored critical areas.

Abstract The oxide and halide perovskite materials with a ABX3 structure exhibit a number of excellent properties, including a high dielectric constant, electrochemical properties, a wide band gap, and a large absorption coefficient. These properties have led to a range of applications, including renewable energy and optoelectronics, where high-performance catalysts are needed. However, it is difficult for a single structure of perovskite alone to simultaneously fulfill the diverse needs of multiple applications, such as high performance and good stability at the same time. Consequently, perovskite nanocomposites have been developed to address the current limitations and enhance their functionality by combining perovskite with two or more materials to create complementary materials. This review paper categorizes perovskite nanocomposites according to their structural composition and outlines their synthesis methodologies, as well as their applications in various fields. These include fuel cells, electrochemical water splitting, CO2 mitigation, supercapacitors, and optoelectronic devices. Additionally, the review presents a summary of their research status, practical challenges, and future prospects in the fields of renewable energy and electronics. Graphical abstract

Abstract Solitons, the distinct balance between nonlinearity and dispersion, provide a route toward ultrafast electromagnetic pulse shaping, high-harmonic generation, real-time image processing, and RF photonic communications. Here we uniquely explore and observe the spatio-temporal breather dynamics of optical soliton crystals in frequency microcombs, examining spatial breathers, chaos transitions, and dynamical deterministic switching – in nonlinear measurements and theory. To understand the breather solitons, we describe their dynamical routes and two example transitional maps of the ensemble spatial breathers, with and without chaos initiation. We elucidate the physical mechanisms of the breather dynamics in the soliton crystal microcombs, in the interaction plane limit cycles and in the domain-wall understanding with parity symmetry breaking from third-order dispersion. We present maps of the accessible nonlinear regions, the breather frequency dependences on third-order dispersion and avoided-mode crossing strengths, and the transition between the collective breather spatio-temporal states. Our range of measurements matches well with our first-principles theory and nonlinear modeling. To image these soliton ensembles and their breathers, we further constructed panoramic temporal imaging for simultaneous fast- and slow-axis two-dimensional mapping of the breathers. In the phase-differential sampling, we present two-dimensional evolution maps of soliton crystal breathers, including with defects, in both stable breathers and breathers with drift. Our fundamental studies contribute to the understanding of nonlinear dynamics in soliton crystal complexes, their spatio-temporal dependences, and their stability-existence zones.

Previous works employ the Large Language Model (LLM) like GPT-3 for knowledge-based Visual Question Answering (VQA). We argue that the inferential capacity of LLM can be enhanced through knowledge injection. Although methods that utilize knowledge graphs to enhance LLM have been explored in various tasks, they may have some limitations, such as the possibility of not being able to retrieve the required knowledge. In this paper, we introduce a novel framework for knowledge-based VQA titled “Prompting Large Language Models with Knowledge-Injection” (PLLMKI). We use vanilla VQA model to inspire the LLM and further enhance the LLM with knowledge injection. Unlike earlier approaches, we adopt the LLM for knowledge enhancement instead of relying on knowledge graphs. Furthermore, we leverage open LLMs, incurring no additional costs. In comparison to existing baselines, our approach exhibits the accuracy improvement of over 1.3 and 1.7 on two knowledge-based VQA datasets, namely OK-VQA and A-OKVQA, respectively.

Abstract Small cell lung cancer (SCLC) is an extremely aggressive cancer with a relatively low median survival rate after diagnosis. Treatment options such as chemotherapy or combination immunotherapy have shown clinical benefits, but resistance and relapse can occur. Antibody–drug conjugates (ADCs), as a novel class of biopharmaceutical compounds, have broad application prospects in the treatment of SCLC. ADCs consist of monoclonal antibodies that specifically target cancer cells and are attached to cytotoxic drugs, allowing for targeted killing of cancer cells while sparing healthy tissues. Current clinical studies focus on Delta-like protein 3 (DLL3), CD56, Trophoblast cell surface antigen 2 (Trop-2), B7-H3, and SEZ6. Although toxicities exceeding expectations have been observed with Rova-T, drugs targeting TROP-2 (Sacituzumab Govitecan), B7-H3 (DS-7300), and SEZ6 (ABBV-011) have shown exciting clinical benefits. In this review, we collect the latest clinical evidence to describe the therapeutic efficacy and safety of ADCs in SCLC and discuss prospects and challenges.

Rapid morphological and socioeconomic changes have accelerated the urbanization process and urban land use transformation in China. Megacities comprise clusters of urban cities and exhibit both newly formed and well-developed urban land use development beyond administrative boundaries. It is necessary to distinguish the changing effects of spatial-varying driving factors on newly formed urban land uses from well-developed built-up areas in megacities. This study proposed a multi-spatial urbanization framework to quantify region-level socioeconomics, cluster-level ecological morphologies, and grid-level urban functional morphologies. A three-level Bayesian hierarchical model was developed to investigate the impacts of multi-spatial driving factors on urban land use transformation in megacities. The study period focused on the urbanization process between 2000 and 2018 in Guangdong–Hong Kong–Macao Greater Bay Area (GBA). Results revealed that compared with well-developed urban built-up land, changing impacts of three-level driving factors in urban land use transformation could be captured based on the proposed Bayesian hierarchical model. The region-level total population was associated with increasing possibilities in forming new residential land than the well-developed ones in 35 districts/counties/cities in GBA. Cluster-level ecological attributes with higher proportion, lower edge density of urban built areas, and lower-degree ecological complexity showed increasing probability on newly formed industrial and public land. Grid-level urban functional factors including public transportation density and shopping/dining distribution exhibited significantly decreasing probability (coefficients: −2.12 to −0.51) on contributing newly formed land uses compared with the well-developed areas, whereas business/industry distribution represented higher (coefficients: 0.99 and 0.15) and lower probabilities (coefficient: −0.22) of forming industrial/public land and residential land separately. This research shows a new attempt to distinguish multi-spatial morphological and socioeconomic effects in urban land use transformation in megacities.

Abstract Chitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein that is induced and regulated by multiple factors during inflammation in enteritis, pneumonia, asthma, arthritis, and other diseases. It is associated with the deterioration of the inflammatory environment in tissues with chronic inflammation caused by microbial infection or autoimmune diseases. The expression of CHI3L1 expression is upregulated in several malignant tumors, underscoring the crucial role of chronic inflammation in the initiation and progression of cancer. While the precise mechanism connecting inflammation and cancer is unclear, the involvement of CHI3L1 is involved in chronic inflammation, suggesting its role as a contributing factor to in the link between inflammation and cancer. CHI3L1 can aggravate DNA oxidative damage, induce the cancerous phenotype, promote the development of a tumor inflammatory environment and angiogenesis, inhibit immune cells, and promote cancer cell growth, invasion, and migration. Furthermore, it participates in the initiation of cancer progression and metastasis by binding with transmembrane receptors to mediate intracellular signal transduction. Based on the current research on CHI3L1, we explore introduce the receptors that interact with CHI3L1 along with the signaling pathways that may be triggered during chronic inflammation to enhance tumorigenesis and progression. In the last section of the article, we provide a brief overview of anti-inflammatory therapies that target CHI3L1.

Abstract Background Cannabidiol (CBD) is a widely available cannabis product with many claims as to potential health benefits including alleviating symptoms related to opioid use disorder (OUD). However, little is known as to how individuals with OUD perceive CBD, to what extent they may already be using CBD, and for what purposes. Methods A survey was conducted among individuals receiving treatment for OUD at the Addiction Institute of Mount Sinai in New York City from July 2021 to August 2023. The survey consisted of demographic questions, questions about opioid use, CBD use, and perceptions regarding CBD. Statistical analysis using ordinal logistic regression was employed to compare perceptions between CBD users and non-users while adjusting for age and race. Results Among 587 respondents, 550 completed the survey. Among all survey completers, 129 (23%) reported a history of using CBD for a variety of reasons including: anxiety (81, 62.8%), pain (65, 50.4%), sleep (63, 48.8%), depression (62, 48.1%), recreational purposes (32, 24.8%), or for other reasons (8, 6.2%). Of note, 22 (17.1%) respondents reported using CBD to control their addiction and 54 (41.9%) reported using CBD to ease opioid withdrawal symptoms. CBD users demonstrated more positive perceptions regarding its legality (β = 0.673, OR = 1.960, 95% CI [1.211, 3.176], p = .006), social acceptance (β = 0.718, OR = 2.051, 95% CI [1.257, 3.341], p = .004), and therapeutic potential compared to non-users. CBD users also had a more positive view of its potential future role in managing addiction (β = 0.613, OR = 1.846, 95% CI [1.181, 2.887], p = .007). Conclusions This study highlights a significant association between CBD usage and progressive views regarding CBD among individuals with OUD, suggesting a growing interest in CBD as a potential adjunctive therapy for individuals in substance use treatment. Some patients are already using CBD for anxiety, pain, sleep, depression, or as a harm reduction intervention to control their addiction or for opioid withdrawal symptoms. These findings underscore the importance of integrating patient perspectives into future research and treatment strategies involving CBD in the context of OUD.

Abstract Metastatic breast cancer (mBC) poses a significant threat to women's health and is a major cause of malignant neoplasms in women. Human epidermal growth factor receptor (HER)3, an integral member of the ErbB/HER receptor tyrosine kinase family, is a crucial activator of the phosphoinositide-3 kinase/protein kinase B signaling pathway. HER3 overexpression significantly contributes to the development of resistance to drugs targeting other HER receptors, such as HER2 and epidermal growth factor receptors, and plays a crucial role in the onset and progression of mBC. Recently, numerous HER3-targeted therapeutic agents, such as monoclonal antibodies (mAbs), bispecific antibodies (bAbs), and antibody–drug conjugates (ADCs), have emerged. However, the efficacy of HER3-targeted mAbs and bAbs is limited when used individually, and their combination may result in toxic adverse effects. On the other hand, ADCs are cytotoxic to cancer cells and can bind to target cells through antibodies, which highlights their use in targeted HER3 therapy for mBC. This review provides an overview of recent advancements in HER3 research, historical initiatives, and innovative approaches in targeted HER3 therapy for metastatic breast cancer. Evaluating the advantages and disadvantages of current methods may yield valuable insights and lessons.

The shaping of urban features is profoundl influenced by the underlying urban context, and architectural features and style management are important parts of the protection and cultivation of urban identity. However, in China, oversight in managing the urban context often results in neglect of the cultural values embedded in architectural aspects at the micro level. This, in turn, contributes to the convergence and disorder of urban architectural features and styles. This study builds upon the significance of the urban context and takes the typical Chinese megacity Wuhan as a case study. First, the research systematically outlines the diachronic development of architectural features and styles in Wuhan and meticulously analyses the prevailing problems. Subsequently, an evaluation is conducted on the efficacy of existing architectural features and style management policies and the approval processes for architectural schemes. Finally, the research formulates a comprehensive architectural feature and style management and implementation system that harmonizes Wuhan’s urban cultural heritage and urban identification characteristics. This paper aims to contribute to the refinement of urban identity management and the preservation of architectural diversity to foster a more cohesive and culturally resonant urban environment in Wuhan.

Abstract Cancer incidence escalates exponentially with advancing age; however, the underlying mechanism remains unclear. In this study, we build a chronological molecular clock at single-cell transcription level with a mammary stem cell-enriched population to depict physiological aging dynamics in female mice. We find that the mammary aging process is asynchronous and progressive, initiated by an early senescence program, succeeded by an entropic late senescence program with elevated cancer associated pathways, vulnerable to cancer predisposition. The transition towards senescence program is governed by a stem cell factor Bcl11b, loss of which accelerates mammary ageing with enhanced DMBA-induced tumor formation. We have identified a drug TPCA-1 that can rejuvenate mammary cells and significantly reduce aging-related cancer incidence. Our findings establish a molecular portrait of progressive mammary cell aging and elucidate the transcriptional regulatory network bridging mammary aging and cancer predisposition, which has potential implications for the management of cancer prevalence in the aged.

Abstract Introduction and objectives In diseases characterized by fibrosis, hepatic stellate cells (HSCs) are mesenchymal cells that play an important role in liver fibrosis. circRNAs are involved in regulating hydatid exocyst formation through miRNA sponge adsorption. The mechanisms of hepatic cystic hydatid outer cyst formation, HSC, and liver fibrosis are unclear. Materials and methods Based on our sequencing data, we validated the mechanism by which circRNA-049637 regulated hepatic cystic hydatid growth and promoted outer fibrocystic wall formation. Results Our results revealed that circRNA_049637 silencing promoted the proliferation of LX-2 human HSCs, affected the cell cycle, and increased the mRNA and protein expression levels of liver fibrosis-related indicators such as α-SMA, COL1A1, COL3A1, and TGFβRII. Conclusions CircRNA_049637 may induce the formation of hepatic hydatid cysts by promoting hepatic fibrosis via HSC activation.

The genus Salmonella contains the most common foodborne pathogens frequently isolated from food-producing animals and is responsible for zoonotic infections in humans and animals. Salmonella infection in humans and animals can cause intestinal damage, resulting in intestinal inflammation and disruption of intestinal homeostasis more severe cases can lead to bacteremia. Pyroptosis, a proinflammatory form of programmed cell death, is involved in many disease processes. Inflammasomes, pyroptosis, along with their respective signaling cascades, are instrumental in the preservation of intestinal homeostasis. In recent years, with the in-depth study of pyroptosis, our comprehension of the virulence factors and effector proteins in Salmonella has reached an extensive level, a deficit persists in our knowledge regarding the intrinsic pathogenic mechanisms about pyroptosis, necessitating a continued pursuit of understanding and investigation. In this review, we discuss the occurrence of pyroptosis induced by Salmonella effectors to provide new ideas for elucidating the regulatory mechanisms through which Salmonella virulence factors and effector proteins trigger pyroptosis could pave the way for novel concepts and strategies in the clinical prevention of Salmonella infections and the treatment of associated diseases.

Abstract The VIM (belonged to E3 ubiquitin ligase) gene family is crucial for plant growth, development, and stress responses, yet their role in salt stress remains unclear. We analyzed phylogenetic relationships, chromosomal localization, conserved motifs, gene structure, cis-acting elements, and gene expression patterns of the VIM gene family in four cotton varieties. Our findings reveal 29, 29, 17, and 14 members in Gossypium hirsutum (G.hirsutum), Gossypium barbadense (G.barbadense), Gossypium arboreum (G.arboreum), and Gossypium raimondii (G. raimondii), respectively, indicating the maturity and evolution of this gene family. motifs among GhVIMs genes were observed, along with the presence of stress-responsive, hormone-responsive, and growth-related elements in their promoter regions. Gene expression analysis showed varying patterns and tissue specificity of GhVIMs genes under abiotic stress. Silencing GhVIM28 via virus-induced gene silencing revealed its role as a salt-tolerant negative regulator. This work reveals a mechanism by which the VIM gene family in response to salt stress in cotton, identifying a potential negative regulator, GhVIM28, which could be targeted for enhancing salt tolerance in cotton. The objective of this study was to explore the evolutionary relationship of the VIM gene family and its potential function in salt stress tolerance, and provide important genetic resources for salt tolerance breeding of cotton.

To study the relationship between DNA methylation and tumour development and provide experimental evidence for the personalized diagnosis and treatment of hepatic carcinoma.

Abstract In this paper, we investigate the shadow and optical appearance of the hairy Reissner–Nordström (RN) black hole illuminated by two toy models of static accretion. The hairy RN black hole was constructed in the gravitation decoupling approach to describe the deformation of a Schwarzschild black hole due to the inclusion of additional arbitrary source (scalar field, tensor field, fluidlike dark matter, etc.). So it is characterized by the parameters: mass (M), deformation factor ( $$\alpha $$ α ), electric charge (Q) and the additional hairy charge ( $$l_o$$ l o )., differentiating from the case in RN black hole. Though the specific background theory that results in this hairy RN black hole is still tricky, here we shall focus on the novel observable features introduced by the hair of this black hole. First, we find that for the hairy RN black hole, the event horizon, radius of photon sphere and critical impact parameter all increase as the increasings of Q and $$l_o$$ l o , but decrease as $$\alpha $$ α grows. Furthermore, the three characterized parameters are found to have significant effects on the photon trajectories, and shadows as well as images of the hairy RN black hole surrounded by the static accretion disk and spherical accretion, respectively. In particular, both Q and $$l_o$$ l o have mutually reinforcing effects on the optical appearance and shadows of the hairy RN black hole, which implies that we may not distinguish the electric charge and hairy charge from the shadow and image of black hole in this scenario. Additionally, because of the competing effects of the charge parameters ( $$Q, l_o$$ Q , l o ) and the deviation parameter $$\alpha $$ α on the observed intensities of brightness, the optical appearance between the hairy RN black hole and RN black hole could have degeneracies, indicating the indistinguishability. Our current results contribute more to the phenomenal aspects which could be helpful to build the background theory of this hairy RN black hole.

Vitrification is the safest and most effective method for treating solid waste incineration residues, and the utilization of vitrified slag can promote recovery of waste resources. By using the response surface methodology to comprehensively consider the impact of three factors – cement substitution ratio, water-binder ratio, and sand rate – on the strength of concrete, the optimal process parameters for predicting the maximum 28-day compressive strength of concrete specimens are determined as follows: 5% cement substitution ratio, 0.69 water-binder ratio, and 40% sand rate. The experiments demonstrate that concrete specimens prepared by partially replacing cement with molten glass slag exhibit excellent mechanical and physicochemical properties. As the curing age increases, the compressive strength of the specimens also enhances. Leaching test results showed that the concrete test block met groundwater Class III quality standards, and the addition of vitrified slag powder reduced the content of calcium hydroxide and improved concrete performance.

The pathogenesis of epilepsy remains unclear; however, a prevailing hypothesis suggests that the primary underlying cause is an imbalance between neuronal excitability and inhibition. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway, which is primarily involved in deoxynucleic acid synthesis and antioxidant defense mechanisms and exhibits increased expression during the chronic phase of epilepsy, predominantly colocalizing with neurons. G6PD overexpression significantly reduces the frequency and duration of spontaneous recurrent seizures. Furthermore, G6PD overexpression enhances signal transducer and activator of transcription 1 (STAT1) expression, thus influencing N-methyl-d-aspartic acid receptors expression, and subsequently affecting seizure activity. Importantly, the regulation of STAT1 by G6PD appears to be mediated primarily through reactive oxygen species signaling pathways. Collectively, our findings highlight the pivotal role of G6PD in modulating epileptogenesis, and suggest its potential as a therapeutic target for epilepsy.

Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, yet effective treatment is lacking. Moreover, the underlying pathomechanisms of ALS remain unclear, with impaired mitophagy function being increasingly recognized as a contributing factor. FUN14 domain-containing protein 1 (FUNDC1) is an autophagy receptor localized to the outer mitochondrial membrane and a mitochondrial membrane protein that mediates mitophagy and therefore considered as important factor in neurodegenerative diseases. However, its specific role in ALS is not yet clear. Therefore, this study aimed to investigate the regulatory role of FUNDC1 in ALS and determine its regulatory mechanisms. ALS transgenic mice were obtained and maintained under standard conditions. Cell lines were generated by stable transfection with hSOD1G93A or control vectors. Mice received intrathecal injections of AAV9 vectors expressing FUNDC1 or EGFP. Motor function was assessed through behavioral tests, and histological and immunostaining analyses were performed. Colocalization analysis was conducted in transfected cells, and protein expression was evaluated via western blotting. We first observed that FUNDC1 was significantly downregulated in the spinal cord tissues of SOD1G93A mice. FUNDC1 overexpression considerably improved locomotor activity and prolonged survival time in SOD1G93A mice. Mechanistically, reduced expression of FUNDC1 resulted in decreased mitophagy, as indicated by decreased recruitment through LC3 in SOD1G93A mice and cellular models. Consequently, this led to increased mitochondrial accumulation and cell apoptosis, exacerbating the ALS phenotype. Furthermore, we identified transcription factor FOXD3 as an essential upstream factor of FUNDC1, resulting in reduced transcription of FUNDC1 in ALS lesions. This study suggests a novel strategy of targeting FUNDC1-mediated mitophagy for developing therapeutic interventions to mitigate disease progression and improve outcomes for ALS patients.

Abstract Objective Immunotherapy, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. However, it can also cause immune‐related adverse events (irAEs). This study aimed to develop a clinically practical animal model of irAEs using BALB/c mice. Methods Subcutaneous tumors of mouse breast cancer 4T1 cells were generated in inbred BALB/c mice. The mice were treated with programmed death‐1 (PD‐1) and cytotoxic t‐lymphocyte antigen 4 (CTLA‐4) inhibitors once every 3 days for five consecutive administration cycles. Changes in tumor volume and body weight were recorded. Lung computed tomography (CT) scans were conducted. The liver, lungs, heart, and colon tissues of the mice were stained with hematoxylin–eosin (H&E) staining to observe inflammatory infiltration and were scored. Serum samples were collected, and enzyme‐linked immunosorbent assay (ELISA) was used to detect the levels of ferritin, glutamic‐pyruvic transaminase (ALT), tumor necrosis factor‐α (TNF‐α), interferon‐gamma (IFN‐γ), and interleukin‐6 (IL‐6). Mouse liver and lung cell suspensions were prepared, and changes in macrophages, T cells, myeloid‐derived suppressor cells (MDSCs), and regulatory (Treg) cells were detected by flow cytometry. Results Mice treated with PD‐1 and CTLA‐4 inhibitors showed significant reductions in tumor volume and body weight. The tissue inflammatory scores in the experimental group were significantly higher than those in the control group. Lung CT scans of mice in the experimental group showed obvious inflammatory spots. Serum levels of ferritin, IL‐6, TNF‐α, IFN‐γ, and ALT were significantly elevated in the experimental group. Flow cytometry analysis revealed a substantial increase in CD3+T cells, Treg cells, and macrophages in the liver and lung tissues of mice in the experimental group compared with the control group, and the change trend of MDSCs was opposite. Conclusions The irAE‐related animal model was successfully established in BALB/c mice using a combination of PD‐1 and CTLA‐4 inhibitors through multiple administrations with clinical translational value and practical. This model offers valuable insights into irAE mechanisms for further investigation.

Organic-inorganic metal halide perovskites solar cells (PSCs) have been emerging as a counterpart or a supplement of silicon-based solar cells. They have shown various interesting optoelectronic properties and impressive power conversion efficiencies, even outperforming the theoretical limits in tandem configurations. However, challenges such as long-term stability and scalable manufacturing remain significant obstacles to commercialization. Key factors like material composition and crystal quality are essential for the reliability and performance of PSCs. Traditional solution-based processes face challenges in scalability and reproducibility. This has drawn attention to vacuum processes, which have been successfully employed in the commercial mass production of optoelectronic devices like displays. Also, recent innovations in automated deposition systems aided by machine learning offer promising solutions. These technological advancements enable rapid optimization of material combinations and manufacturing processes, facilitating a transition from lab-scale prototypes to industrial applications. This review highlights the converging efforts from multiple disciplines—materials science, process engineering and machine learning—that are essential for the transition from experimental validation to commercial, sustainable energy solutions. In summary, the work sets a path forward, where collective expertize can address lingering challenges, making clean, accessible, and affordable energy an attainable goal.

IntroductionPeripartal cows are susceptible to a negative energy balance due to inadequate nutrient intake and high energy requirements for lactation. Improving the energy metabolism of perinatal dairy cows is crucial in increasing production in dairy cows.MethodsIn this study, we investigated the impact of rumen-protected branched-chain amino acid (RPBCAA) on the production performance, energy and lipid metabolism, oxidative stress, and immune function of primiparous dairy cows using metabolomics through a single-factor experiment. Twenty healthy primiparous Holstein cows were selected based on body condition scores and expected calving date, and were randomly divided into RPBCAA (n = 10) and control (n = 10) groups. The control group received a basal diet from calving until 21 d in milk, and the RPBCAA group received the basal diet and 44.6 g/d RPLeu, 25.14 g/d RPIle, and 25.43 g/d RPVal.ResultsIn comparison to the control group, the supplementation of RPBCAA had no significant effect on milk yield and milk composition of the dairy cows. Supplementation with RPBCAA significantly increased the concentrations of insulin, insulin growth factor 1, glucagon, and growth hormones, which are indicators of energy metabolism in postpartum cows. The very low density lipoprotein, fatty acid synthase, acetyl coenzyme A carboxylase, and hormone-sensitive lipase contents of the RPBCAA group were significantly greater than that of the control group; these metrics are related to lipid metabolism. In addition, RPBCAA supplementation significantly increased serum glutathione peroxidase and immunoglobulin G concentrations and decreased malondialdehyde concentrations. Liquid chromatography–mass spectrometry (LC-MS) analysis revealed 414 serum and 430 milk metabolic features. Supplementation with RPBCAA primarily increased concentrations of amino acid and lipid metabolism pathways and upregulated the abundance of serotonin, glutamine, and phosphatidylcholines.DiscussionIn summary, adding RPBCAA to the daily ration can influence endocrine function and improve energy metabolism, regulate amino acid and lipid metabolism, mitigate oxidative stress and maintain immune function on primiparous cows in early lactation.

Binge drinking exerts cardiac toxicity through various mechanisms, including oxidative stress and inflammation. NLRP3 inflammasomes possess both pro- and anti-inflammatory properties, although the role of NLRP3 in ethanol-induced cardiotoxicity remains unknown. This study is designed to examine the role of NLRP3 inflammasome in acute ethanol cardiotoxicity and the underlying mechanisms of action. Nine- to twelve-week-old adult male C57BL/6 mice are administered with ethanol (1.5 g/kg, twice daily, i.p.) for 3 days. A cohort of control and ethanol-challenged mice are treated with the NLRP3 inhibitor MCC950 (10 mg/kg/day, i.p., days 1 and 3). Myocardial geometry and function are monitored using echocardiography and cardiomyocyte edge-detection techniques. Levels of NLRP3 inflammasome, mitophagy and apoptosis are evaluated by western blot analysis and immunofluorescence techniques. Acute ethanol challenge results in abnormally higher cardiac systolic function, in conjunction with deteriorated cardiac diastolic function and cardiomyocyte contractile function. Levels of NLRP3 inflammasome and apoptosis are elevated, and mitophagy flux is blocked (elevated Pink1-Parkin and LC3B along with diminished p62 and Rab7) in mice receiving acute ethanol challenge. Although MCC950 does not elicit a notable effect on myocardial function, apoptosis or inflammasome activation in the absence of ethanol exposure, it effectively rescues acute ethanol cardiotoxicity, as manifested by restored myocardial and cardiomyocyte functional homeostasis, suppressed NLRP3 inflammasome activation and apoptosis, and improved mitophagy flux. Our data further suggest that FBXL2, an E3 ubiquitin ligase associated with mitochondrial homeostasis and mitophagy, is destabilized due to proteasomal degradation of caspase-1 by ethanol-induced hyperactivation of NLRP3-caspase-1 inflammasome signaling, resulting in mitochondrial injury and apoptosis. These findings denote a role for NLRP3 inflammasome in acute ethanol exposure-induced cardiotoxicity in an FBXL2-dependent manner and the therapeutic promise of targeting NLRP3 inflammasome for acute ethanol cardiotoxicity.

Abstract In this paper, we investigate the gravitational lensing effects in the weak and strong field limits of a static black hole with conformally coupled scalar field. In the weak field limit, with the use of Gauss–Bonnet theorem we calculate the deflection angle of the light. It is found that comparing to Schwarzschild and Reissner–Nordstr $$\ddot{\text {o}}$$ o ¨ m (RN) black holes in general relativity, the weak deflection angle can be enhanced/suppressed by the scalar hair. In the strong field limit, we first compute the light deflection angle via calculating the lensing coefficients, all of which increase as the values of electric and scalar charges increase. Then we evaluate the lensing observables in strong field regime by supposing the hairy black hole as the candidate of M87* and SgrA* supermassive black holes, respectively. We find that the scalar hair has significant influences on various observables. In particular, the lensing observables of the charged black hole with positive scalar hair and RN black hole have degeneracy, which will be broken by the case with negative scalar hair. Our theoretical findings imply that it is feasible to employ the gravitational lensing effects as a probe of Einstein–Maxwell theory with negative scalar field differentiating from general relativity, once the future astrophysical observation is precise enough.

AP2/ERF transcription factors play important roles in plant growth, development and response to abiotic stress. In order to explore the response of AvAP2/ERF genes in Aquilegia vulgaris to salt stress, based on the transcriptome data obtained under salt stress in previous experiments, the AP2/ERF gene family in A. vulgaris were screened by bioinformatic methods, and their physical and chemical properties, conserved motifs, phylogenetic relations and expression changes of these genes in leaves and roots under salt stress were analyzed, etc. The expression of candidate genes was verified by qRT-PCR. The results were as follows：(1) 86 AvAP2/ERF genes were identified which encoded 132-722 amino acids, with molecular weight of 14 763.30-79 069.47 Da and isoelectric point ranged from 4.49 to 9.68. Most of them were slightly acidic proteins and all of them were hydrophilic. Most of AvAP2/ERF were localized in nucleus. (2)The similarity of secondary structure was high, which was proportionally composed of random coil and α-helix. The members all contained AP2 domains, and two conserved motifs were predicted. (3) Under different stages of salt treatment, there were 71 AvAP2/ERF genes responded to salt stress. There were 18 and 19 differentially expressed genes in leaves and roots, respectively. There were 86 AP2/ERF genes of A. vulgaris were divided into five subfamilies clustering with A. thaliana; the AP2/ERF genes of A. vulgaris and Arabidopsis thaliana were clustered into five subfamilies and 15 subgroups. Through expression analysis and homology relationship, AvAP2/ERF-56, AvAP2/ERF-61 and AvAP2/ERF-80 of them might be involved in salt resistance, and the qRT-PCR results were consistent with sequencing expression trends. The results of this study provides a reliable reference for further research on the function and stress response mechanism of AP2/ERF gene in Aquilegia vulgaris.

Abstract Cytokinin oxidase/dehydrogenase (CKX) is a key regulatory enzyme for the irreversible degradation of the plant hormone cytokinin (CK), which is important in growth and development and response to abiotic stresses in cotton. In this study, 27, 28, 14 and 14 CKXs were screened by FAD structural domain and cytokinin binding structural domain in Gossypium hirsutum, Gossypium barbadense, Gossypium arboreum and Gossypium raimondii, respectively. Their phylogenetic relationships and expression patterns were analyzed, and most GhCKXs were found to be tissue-specific and responsive to various abiotic stresses such as cold, heat, salt and PEG. GhCKX6b-Dt was selected for gene silencing in evolutionary branch II for salt stress, because its expression increased after salt stress in cotton plants. An increase in PRO and MDA content and a decrease in SOD activity due to this gene were found after inducing salt stress, contributing to oxidative damage and decreased salt tolerance. In this study, CKXs were analyzed to reveal the possible role of GhCKXs against abiotic stresses in cotton, which provides a basis for further understanding of the biological functions of CK in plants such as growth and development and stress resistance.

Abstract Background Inositol monophosphates (IMP) are key enzymes in the ascorbic acid (AsA) synthesis pathways, which play vital roles in regulating plant growth and development and stresses tolerance. To date, no comprehensive analysis of the expression profile of IMP genes and their functions under abiotic stress in cotton has been reported. Results In this study, the genetic characteristics, phylogenetic evolution, cis-acting elements and expression patterns of IMP gene family in cotton were systematically analyzed. A total of 28, 27, 13 and 13 IMP genes were identified in Gossypium hirsutum (G. hirsutum), Gossypium barbadense (G. barbadense), Gossypium arboreum (G. arboreum), and Gossypium raimondii (G. raimondii), respectively. Phylogenetic analysis showed that IMP family genes could cluster into 3 clades. Structure analysis of genes showed that GhIMP genes from the same subgroup had similar genetic structure and exon number. And most GhIMP family members contained hormone-related elements (abscisic acid response element, MeJA response element, gibberellin response element) and stress-related elements (low temperature response element, defense and stress response element, wound response element). After exogenous application of abscisic acid (ABA), some GhIMP genes containing ABA response elements positively responded to alkaline stress, indicating that ABA response elements played an important role in response to alkaline stress. qRT-PCR showed that most of GhIMP genes responded positively to alkaline stress, and GhIMP10D significantly upregulated under alkaline stress, with the highest up-regulated expression level. Virus-induced gene silencing (VIGS) experiment showed that compared with 156 plants, MDA content of pYL156:GhIMP10D plants increased significantly, while POD, SOD, chlorophyII and AsA content decreased significantly. Conclusions This study provides a thorough overview of the IMP gene family and presents a new perspective on the evolution of this gene family. In particular, some IMP genes may be involved in alkaline stress tolerance regulation, and GhIMP10D showed high expression levels in leaves, stems and roots under alkaline stress, and preliminary functional verification of GhIMP10D gene suggested that it may regulate tolerance to alkaline stress by regulating the activity of antioxidant enzymes and the content of AsA. This study contributes to the subsequent broader discussion of the structure and alkaline resistance of IMP genes in cotton.

bZIP transcription factors play important roles in regulating plant development and stress responses. Although bZIPs have been identified in many plant species, there is little information on the bZIPs in Chrysanthemum. In this study, bZIP TFs were identified from the leaf transcriptome of C. mongolicum, a plant naturally tolerant to drought. A total of 28 full-length bZIP family members were identified from the leaf transcriptome of C. mongolicum and were divided into five subfamilies based on their phylogenetic relationships with the bZIPs from Arabidopsis. Ten conserved motifs were detected among the bZIP proteins of C. mongolicum. Subcellular localization assays revealed that most of the CmbZIPs were predicted to be localized in the nucleus. A novel bZIP gene, designated as CmbZIP9, was cloned based on a sequence of the data of the C. mongolicum transcriptome and was overexpressed in tobacco. The results indicated that the overexpression of CmbZIP9 reduced the malondialdehyde (MDA) content and increased the peroxidase (POD) and superoxide dismutase (SOD) activities as well as the expression levels of stress-related genes under drought stress, thus enhancing the drought tolerance of transgenic tobacco lines. These results provide a theoretical basis for further exploring the functions of the bZIP family genes and lay a foundation for stress resistance improvement in chrysanthemums in the future.

Urban residential areas significantly influence outdoor thermal comfort through architectural morphology. This study concentrates on the multi-objective optimization of the thermal comfort environment in residential areas, with a focus on Yulin—a city in the cold, inland region of Northwestern China. Yulin is characterized by its distinctly defined seasons, particularly harsh and windy conditions in the spring, which significantly impact thermal comfort. Utilizing field surveys, characteristics of scale and layout from high-rise residential areas in Yulin were extracted to formulate design strategies adapted to local climates. The Universal Thermal Climate Index (UTCI) served as the optimization criterion, and genetic algorithms, integrated with parametric modeling software, generated multiple layout schemes. These were refined through the Pareto evolutionary algorithm II to optimize thermal comfort across seasons. Furthermore, the Sobol’ sensitivity analysis method was employed to assess the impact of key parameters on outdoor thermal comfort, identifying crucial layout design elements. The optimization improved UTCI values for different seasons, ensuring year-round comfort. Specifically, summer UTCI improved to 25.51, while winter and spring values reached optimal values of −14.02 and −6.41, demonstrating enhanced thermal retention and reduced wind exposure. Sobol’ sensitivity analysis identified building length, orientation, and density as key parameters, highlighting their critical impact on thermal comfort. This study offers practical guidelines for urban residential area design in similar climatic zones, aligning architectural planning with environmental sustainability and enhancing thermal comfort effectively. This study provides practical guidelines for the design of residential areas in cold inland—seasonal windy—regions and other similar climatic zones, aligning building morphology design with environmental sustainability and enhancing thermal comfort effectively.

Iris typhifolia Kitag is a perennial herbaceous species with high ornamental and applied value. Elucidating the mechanism of saline–alkali tolerance in Iris is crucial for their promotion in saline–alkali areas. Saline–alkali stress is one of the factors that affects plant growth, which has become a significant global issue. In this study, we measured the physiological and biochemical indexes of I. typhifolia, through germination and potting trials, to evaluate the resistance of I. typhifolia to different levels of artificial saline–alkali stress (0, 50, 100, 150, and 200 mmol·L−1). The results showed that artificial saline–alkali stress negatively impacted germination parameters, cell membrane integrity, and photosynthetic parameters. Different trends in osmoregulatory substances and endogenous hormones were observed. It was shown that I. typhifolia had a potential adaptability to the saline–alkali environment by enhancing its internal defense mechanism. Based on regression analyses, the germination threshold of I. typhifolia was calculated to be 87.15 mmol·L−1, which provided a theoretical basis for the application in soil saline–alkalization areas.

ObjectiveTo explore the effects of comprehensive nursing during treatment on incidence of complications and nursing satisfaction in patients with neuromyelitis optica （NMO）. MethodsA total of 96 NMO patients admitted to Beijing Tiantan Hospital from June 2020 to May 2022 were selected and randomly divided into control group （with routine nursing, n=48） and observation group （with comprehensive nursing, n=48）. The functional disability, daily living ability, self-management behavior, incidence of complications and nursing satisfaction were compared between two groups. ResultsAfter nursing, the extended disability status scale （EDSS） score in observation group was significantly lower than that in control group and before nursing （P＜0.05）, and the Barthel index （BI） score and self-management behaviors score were significantly higher than those in control group and before nursing （P＜0.05）. In observation group, the total nursing satisfaction （95.83%vs77.08%, χ2=7.207, P=0.007） significantly increased, and the incidence of complications （6.25%vs 20.83%, χ2=4.359, P=0.037） significantly decreased compared with those in control group. ConclusionComprehensive nursing is more conducive to restoring neurological function and activities of daily living, improving the self-management behaviors and the nursing satisfaction of patients and reducing the occurrence of complications.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1–BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination–deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Abstract Epilepsy is a widespread neurological disorder affecting more than 65 million people, but the mechanisms of epilepsy remains unknown. Abnormal synaptic transmission has a crucial role in the occurrence and development of epilepsy. Here, we found that syntabulin, a neuronal transporter, was mainly localized in neurons, and its expression was increased in epileptic tissues. Knockdown of syntabulin increased susceptibility and severity of epilepsy, whereas overexpression of syntabulin had the opposite effect. Mechanistically, in the epileptic brain tissue, syntabulin mainly translocated syntaxin 1B (STX1B) rather than syntaxin 1A (STX1A) to the presynaptic membrane, which resulted in increased presynaptic transmitter release. Further studies showed that syntabulin had a more significant effect on presynaptic functionality of GABAergic activity over that of excitatory synapses and resulted in an excitation/inhibition (E/I) imbalance, thereby regulating the epileptic phenotype. In addition, we found that the increased expression of syntabulin in epileptic brain tissue was mainly regulated by transcription factor TFAP2A. In summary, syntabulin plays a protective role in epilepsy by maintaining a proper E/I balance in the hippocampus.

Background With the successful development of modern immunotherapy, immune checkpoint inhibitors (ICIs) are currently considered potential therapeutic options for patients with cancer. However, the therapeutic potential of ICIs in human cancer is mainly limited by their systemic toxicity and low response rate, which suggests the necessity of local drug delivery with an effective vector and reshaping the immunosuppressive tumor microenvironment (TME) to enhance ICI therapy. Here, we constructed a novel double-gene recombinant oncolytic adenovirus named RCAd-LTH-shPD-L1 based on the RCAd virus platform armed with a DNA fragment encoding an anti-VEGF antibody and shRNA to inhibit PD-L1 expression.Methods The correct assembly of RCAd-LTH-shPD-L1 was characterized by analyzing its secretion, antigen specificity, and replication using western blotting, ELISA and quantitative PCR, respectively. The in vitro effects of RCAd-LTH-shPD-L1 on cell proliferation, vasculogenic, and cell migration were assessed. Antitumor effects and therapeutic mechanisms were evaluated in vivo using immunodeficient and humanized immune system mouse models. The TME was studied by ELISA, immunohistochemistry and flow cytometry.Results RCAd-LTH-shPD-L1 cells secreted anti-VEGF antibodies and inhibited the expression of PD-L1 in cancer cells. Moreover, RCAd-LTH-shPD-L1 exerted a specific cytotoxic effect on human cancer cells, but not on murine cancer cells or normal human cells. RCAd-LTH-shPD-L1 elicited a more potent antitumor effect in an immunodeficient mouse model and a humanized immune system mouse model than RCAd-shPD-L1, as demonstrated by the significant decrease in tumor growth. Furthermore, RCAd-LTH-shPD-L1 modulated the TME, which led to lymphocyte infiltration and alteration of their immune phenotype, as characterized by downregulation of anoxic factor HIF-1α and angiogenesis marker CD31, upregulation of cytokine such as IFN-γ, IL-6 and IL-12.Conclusions In summary, our data demonstrated that the localized delivery of anti-VEGF antibodies and shPD-L1 by engineered RCAd-LTH-shPD-L1 is a highly effective and safe strategy for cancer immunotherapy. Moreover, the data underscore the potential of combining local virotherapy and anti-angiogenic therapy with ICIs as an effective TME therapy for poorly infiltrating tumors.

A-galactosidases (AGALs), the oligosaccharide (RFO) catabolic genes of the raffinose family, play crucial roles in plant growth and development and in adversity stress. They can break down the non-reducing terminal galactose residues of glycolipids and sugar chains. In this study, the whole genome of AGALs was analyzed. Bioinformatics analysis was conducted to analyze members of the AGAL family in Gossypium hirsutum, Gossypium arboreum, Gossypium barbadense, and Gossypium raimondii. Meanwhile, RT-qPCR was carried out to analyze the expression patterns of AGAL family members in different tissues of terrestrial cotton. It was found that a series of environmental factors stimulated the expression of the GhAGAL3 gene. The function of GhAGAL3 was verified through virus-induced gene silencing (VIGS). As a result, GhAGAL3 gene silencing resulted in milder wilting of seedlings than the controls, and a significant increase in the raffinose content in cotton, indicating that GhAGAL3 responded to NaCl stress. The increase in raffinose content improved the tolerance of cotton. Findings in this study lay an important foundation for further research on the role of the GhAGAL3 gene family in the molecular mechanism of abiotic stress resistance in cotton.

Abstract Alcoholic liver disease (ALD) is an ignored global issue of public health. It is urgent for searching bioactive foods to prevent ALD. Zhenjiang aromatic vinegar (ZAV) contained antioxidant compounds, including polyphenols, flavonoids, and melanoidins. The mechanism of ZAV on preventing acute liver injury was evaluated in alcohol‐treated mice. Our results showed that ZAV ameliorated morphological damage by hematoxylin and eosin and Oil Red O staining in alcohol‐treated liver. ZAV relieved symptoms of ALD, which presented as decreased serum triacylglycerol, total cholesterol, alanine transaminase, and aspartate aminotransferase levels. In addition, ZAV treatment inhibited hepatic oxidative stress levels by downregulating reactive oxygen species generation, and the oxidative products (malonaldehyde, 4‐hydroxynonenal, and 8‐hydroxydeoxyguanosine), and upregulating catalase, superoxide dismutase, glutathione, and glutathione peroxidase. ZAV further reduced production of tumor necrosis factor‐α and monocyte chemoattractant protein‐1, and elevated levels of interleukin‐4 and transforming growth factor‐β indicating the inhibition of alcohol‐induced inflammation. Furthermore, ZAV treatment increased expression levels of autophagy‐associated proteins in ALD mice by western blot, which participated in anti‐ALD effect of ZAV. These findings demonstrate that ZAV could be an alternative for ALD intervention by regulating oxidative stress and autophagy.

The complex underground public space brings challenge on pathfinding cognition. This research took Luoxiong Road Station in Wuhan as experimental site, using eye movement and electroencephalogram (EEG) synchronous detection, through pathway analysis and space-time fault method, exploring relationship between pathfinding cognition and complex underground public space. It was found that pathfinding habits and pathfinding decision-making were mainly affected by personal factors and environmental factors, respectively. Pathfinders influenced by personal factors, had behaviors such as left-walking or right-walking tendency, and the ratio of brain wave β/α was low (impression ratio ≤1). Pathfinders influenced by environmental factors, interested in the other side situation, vertical traffic and so on, and the ratio of brain wave β/α was high (impression ratio >1), with the frontal and parietal occipital lobe regions of brain being more active. These conclusions provided theoretical and data supplements for underground rail transit environment optimizing design in future.

AbstractBackground Decreased serum hemoglobin (Hb) level is associated with Immunoglobulin A nephropathy (IgAN) progression. However, whether serum Hb level is an independent prognostic factor of IgAN remains controversial. Herein, we aimed to investigate the prognostic value of serum Hb level in IgAN.Methods The Cochrane Library, Embase, PubMed and Open Grey databases were systematically searched and reviewed. Kidney disease progression of IgAN was defined as a doubling of serum creatinine (SCr), a 30% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), or death. We evaluated the hazard ratio (HR) between serum Hb level and the incidence of kidney disease progression in IgAN before and after adjusting for relevant covariates.Results We included nine studies with 10006 patients in the meta-analysis. As a continuous variable, we found that serum Hb was an independent prognostic factor of IgAN [unadjusted HR = 0.89, 95% confidence interval (CI) = 0.84–0.95, I2 = 98%; adjusted HR = 0.85, 95% CI = 0.79–0.91, I2 = 0%]. The sensitivity analysis confirmed the stability of these results. Consistently, as a dichotomous variable defined as the below/above cutoff for anemia, we observed a positive correlation between serum Hb and kidney disease progression in IgAN (unadjusted HR = 2.12, 95% CI = 1.44–3.12, I2 = 79%; adjusted HR = 1.65, 95% CI = 1.20–2.27, I2 = 0%).Conclusion Serum Hb level was independently correlated with the incidence of kidney disease progression in IgAN.

Telomerase Cajal body protein 1 (TCAB1) is closely related to the occurrence, development and prognosis of tumors, and may affect the sensitivity of tumor radiotherapy. There are no reports about the effect of TCAB1 gene expression on proliferation and apoptosis of HEPG2 cells. We plan to investigate whether silencing TCAB1 using siRNA is helpful for the diagnosis and treatment of hepatocellular carcinoma.

Abstract Epitaxy technology produces high-quality material building blocks that underpin various fields of applications. However, fundamental limitations exist for conventional epitaxy, such as the lattice matching constraints that have greatly narrowed down the choices of available epitaxial material combinations. Recent emerging epitaxy techniques such as remote and van der Waals epitaxy have shown exciting perspectives to overcome these limitations and provide freestanding nanomembranes for massive novel applications. Here, we review the mechanism and fundamentals for van der Waals and remote epitaxy to produce freestanding nanomembranes. Key benefits that are exclusive to these two growth strategies are comprehensively summarized. A number of original applications have also been discussed, highlighting the advantages of these freestanding films-based designs. Finally, we discuss the current limitations with possible solutions and potential future directions towards nanomembranes-based advanced heterogeneous integration. Graphical Abstract

Abstract Background Non-small cell lung cancer (NSCLC) is the main type of the most common malignant tumor in the world. Previous studies have shown that the expression level of mitochondrial creatine kinase 1 (CKMT1) is abnormal in NSCLC, but the mechanism of its effect remains unclear. Therefore, in this study, we intend to clarify the potential mechanism of CKMT1 in NSCLC and provide the theoretical basis for the clinical application of CKMT1. Methods The function of CKMT1 in NSCLC was identified by analyzing the GEO dataset and evaluating using in vitro and in vivo models. Protein mass spectrometry was used to find proteins interacting with CKMT1, and Co-immunoprecipitation (Co-IP) and GST-pull down experiments were used to verify the interaction between proteins. The immunofluorescence (IF) assay was used to explore the functional position of CKMT1 in cells. The effect of CKMT1 expression level on the efficacy of paclitaxel (TAX) in the treatment of NSCLC was analyzed by a combined TAX experiment in vivo and in vitro. Results CKMT1 expression was increased in NSCLC and CKMT1 promoted the proliferation of NSCLC cells in vitro and in vivo. CKMT1 knockdown resulted in a significantly increased G0/G1 fraction and decreased S phase cell fraction, indicating G1 phase arrest. Mechanically, the cyclin-dependent kinase 4 (CDK4) was identified to interact with CKMT1, and the crucial binding areas were focused on the DH domain of CKMT1 and the N- and C-terminal of CDK4. A fraction of the CDK4 proteins colocalize and interact with the CKMT1 at mitochondria, the level of phosphorylated CDK4 was regulated by CKMT1. Hence, the decrease in CKMT1 expression level could increase the antitumor effect of G2/M cell cycle antagonist-TAX in NSCLC in vitro and in vivo. Conclusions CKMT1 could interact with CDK4 in mitochondria and regulate the phosphorylated level of CDK4, thus contributing to the proliferation and cell cycle transition of NSCLC cells. And CKMT1 could be a potential target to improve the sensitivity of chemotherapy based on TAX.

Non-noble transition metal oxides (TMOs) are promising catalysts with improved catalytic activity and stability in oxygen evolution reaction (OER). However, the structural complexity of TMO-based electrocatalysts renders the determination of the active sites and OER mechanisms challenging. Here, we demonstrate that the OER activity of Co-doped one-dimensional W18O49 (Co-W18O49) is intrinsically dominated by the surface structure and electronic properties of the octahedral sites and Co–O–W bonds. Compared with RuO2 and W18O49 heterogeneous electrocatalysts, Co-W18O49 exhibits higher turnover frequency, attaining 1.97 s−1 at 500 mV overpotential. The results indicate that Co substitution contributes to the localized charge distribution of the active octahedral sites constructed by the Co–O–W bonds under OER conditions. Here, we determine the mechanism of TMOs for the OER, which may be applied to various other TMOs for OER electrocatalyst design.

Abstract Background Mitochondrial dysfunction is considered to be an important contributor in podocyte injury under diabetic conditions. The BaoShenTongLuo (BSTL) formula has been shown to reduce podocyte damage and postpone the progression of diabetic kidney disease (DKD). The potential mechanisms underlying the effects of BSTL, however, have yet to be elucidated. In this study, we aimed to investigate whether the effects of BSTL are related to the regulation of mitochondrial biogenesis via the adenosine monophosphate-activated protein kinase (AMPK) pathway. Methods High-Performance Liquid Chromatography Electrospray Ionization Mass Spectrometer (HPLC–ESI–MS) analysis was performed to investigate the characteristics of pure compounds in BSTL. db/db mice and mouse podocyte clone-5 (MPC5) cells were exposed to high glucose (HG) to induce DKD and podocyte damage. Body weight, random blood glucose, urinary albumin/creatinine ratio (UACR), indicators of renal function and renal histological lesions were measured. Markers of podocyte injury, mitochondrial morphology, mitochondrial deoxyribonucleic acid (mtDNA) content, mitochondrial respiratory chain complexes activities, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) levels were assessed. Protein expressions of AMPK, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), transcription factor A (TFAM), mitochondrial fusion protein 2 (MFN2) and dynamin-related protein 1 (DRP1) were also detected. MPC5 cells were transfected with AMPKα small interfering RNA (AMPKα siRNA) to determine the underlying mechanisms of BSTL improvement of mitochondrial function under diabetic conditions. Results In vivo, treatment with BSTL reduced the UACR levels, reversed the histopathological changes in renal tissues, and alleviated the podocyte injury observed in db/db mice. After BSTL treatment, the decreased mtDNA content and mitochondrial respiratory chain complex I, III, and IV activities were significantly improved, and these effects were accompanied by maintenance of the protein expression of p-AMPKαT172, PGC-1α, TFAM and MFN2. The in vitro experiments also showed that BSTL reduced podocyte apoptosis, suppressed excessive cellular ROS production, and reversed the decreased in MMP that were observed under HG conditions. More importantly, the effects of BSTL in enhancing mitochondrial biogenesis and reducing podocyte apoptosis were inhibited in AMPKα siRNA-treated podocytes. Conclusion BSTL plays a crucial role in protecting against podocyte injury by regulating the AMPK-mediated mitochondrial biogenesis in DKD.

Abstract Objective We aimed to explore the association between thyroid hormones and different stages of diabetic kidney disease (DKD) in Chinese adults. Methods This is a retrospective study involving 2,832 participants. DKD was diagnosed and classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) categories. Effect sizes are expressed as odds ratio (OR) with 95% confidence interval (CI). Results After propensity score matching (PSM) on age, gender, hypertension, hemoglobin A1c(HbA1c), total cholesterol (TC), serum triglyceride (TG) and duration of diabetes, per 0.2 pg/mL increment in serum free triiodothyronine (FT3) was significantly associated with 13%, 22% and 37% reduced risk of moderate-risk (OR, 95% CI, P: 0.87, 0.70–0.87,

Multi-relational graph neural networks (GNNs) have found widespread application in tasks involving enhancing knowledge representation and knowledge graph (KG) reasoning. However, existing multi-relational GNNs still face limitations in modeling the exchange of information between predicates. To address these challenges, we introduce Relgraph, a novel KG reasoning framework. This framework introduces relation graphs to explicitly model the interactions between different relations, enabling more comprehensive and accurate handling of representation learning and reasoning tasks on KGs. Furthermore, we design a machine learning algorithm based on the attention mechanism to simultaneously optimize the original graph and its corresponding relation graph. Benchmark and experimental results on large-scale KGs demonstrate that the Relgraph framework improves KG reasoning performance. The framework exhibits a certain degree of versatility and can be seamlessly integrated with various traditional translation models.

This paper is dedicated to studying the existence results of solutions to the nonlinear coupled system of Hilfer fractional differential equations and inclusions, with multi-strip and multi-point mixed boundary conditions. Through tools such as the Leray-Schauder alternative and the nonlinear alternative of Leray-Schauder type, continuous and measurable selection theorems, along with Leray-Schauder degree theory, the main results can be obtained. The Hilfer fractional differential system has practical implications for specific physical phenomena. Examples are provided to clarify the application of our main results.

The judicious configuration of predicates is a crucial but often overlooked aspect in the field of knowledge graphs. While previous research has primarily focused on the precision of triples in assessing knowledge graph quality, the rationality of predicates has been largely ignored. This paper introduces an innovative approach aimed at enhancing knowledge graph reasoning by addressing the issue of predicate polysemy. Predicate polysemy refers to instances where a predicate possesses multiple meanings, introducing ambiguity into the knowledge graph. We present an adaptable optimization framework that effectively addresses predicate polysemy, thereby enhancing reasoning capabilities within knowledge graphs. Our approach serves as a versatile and generalized framework applicable to any reasoning model, offering a scalable and flexible solution to enhance performance across various domains and applications. Through rigorous experimental evaluations, we demonstrate the effectiveness and adaptability of our methodology, showing significant improvements in knowledge graph reasoning accuracy. Our findings underscore that discerning predicate polysemy is a crucial step towards achieving a more dependable and efficient knowledge graph reasoning process. Even in the age of large language models, the optimization and induction of predicates remain relevant in ensuring interpretable reasoning.