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Abstract Synovial sarcoma (SS) is driven by a unique t(18;X) chromosomal translocation resulting in expression of the SS18-SSX fusion oncoprotein, a transcriptional regulator with both activating and repressing functions. However, the manner in which SS18-SSX contributes to the development of SS is not entirely known. Here, we show that SS18-SSX drives the expression of Preferentially Expressed Antigen in Melanoma (PRAME), which is highly expressed in SS but whose function remains poorly understood. The fusion protein directly binds and activates the PRAME promoter and we found that expression of SS18-SSX and PRAME are positively correlated. We provide evidence that PRAME modulates retinoic acid (RA) signaling, forming a ternary complex with the RA receptor α (RARα) and the Enhancer of Zeste Homolog 2 (EZH2). Knockdown of PRAME suppressed the response to all-trans retinoic acid (ATRA) supporting PRAME’s role in modulating RA-signaling. Notably, we demonstrate that combined pharmacological inhibition of EZH2 and treatment with ATRA reconstituted RA signaling followed by reduced proliferation and induction of cellular senescence. In conclusion, our data provides new insights on the role of the SS18-SSX fusion protein in regulation of PRAME expression and RA signaling, highlighting the therapeutic potential of disrupting the RARα-PRAME-EZH2 complex in SS. Schematic presentation of the proposed model. A The RARα-PRAME-EZH2 ternary complex in SS. The fusion SS18-SSX oncoprotein binds to the PRAME promoter and activates its expression. PRAME in turn interacts with RARα-RXR heterodimers as well as with EZH2, and the complex binds to retinoic acid response elements (RAREs) in the DNA. This results in transcriptional repression of retinoic acid (RA) responsive genes and thus inhibition of RA-signaling, allowing tumor cell proliferation. B Therapeutic strategy. Treatment with an EZH2 inhibitor, such as GSK343, or activation of RAR receptors via all-trans retinoic acid (ATRA), disrupts the RARα-PRAME-EZH2 ternary complex and restores RA-signaling. Exposure to GSK343 or ATRA results in inhibition of cell proliferation and induction of cellular senescence, where GSK343 shows a dominant effect. The Figure was created with Biorender.com.

Litchi downy blight, caused by the plant pathogenic oomycete Peronophythora litchii, is one of the most devastating diseases on litchi and resulted in huge economic losses. Autophagy plays an essential role in the development and pathogenicity of the filamentous fungi. However, the function of autophagy in oomycetes remain elusive. Here, an autophagy-related protein Atg3 homolog PlAtg3 was identified and characterized in P. litchii. The absence of PlATG3 through the CRISPR/Cas9 gene replacement strategy compromised vegetative growth and sexual/asexual development. Cytological analyses revealed that the deletion of PlATG3 impaired autophagosome formation with monodansylcadaverine (MDC) staining and significantly disrupted zoospore release due to defects of sporangial cleavage with FM4-64 staining. Atg8 is considered to be an autophagy marker protein in various species. Western blot analysis indicated that PlAtg3 is involved in degradation of PlAtg8-PE. Interestingly, PlAtg3 was unable to interact with PlAtg8 in yeast two hybrid (Y2H) assays, possibly due to the absence of the Atg8 family interacting motif (AIM) in PlAtg3. Furthermore, pathogenicity assays revealed that the deletion of PlATG3 considerably reduced the virulence of P. litchii. Taken together, our data reveal that PlAtg3 plays an important role in radial growth, asexual/sexual development, sporangial cleavage and zoospore release, autophagosome formation, and pathogenicity in P. litchii. This study contributes to a better understanding of the pathogenicity mechanisms of P. litchii and provides insights for the development of more effective strategies to control oomycete diseases.

Abstract Lloyd's mirror effect is a spatial interference phenomenon that results from the coherent combination of direct and surface‐reflected propagation paths. The higher‐order vertical sound intensities of the interference sound field contain source depth information, and the relationship between these higher‐order sound intensities can be employed to estimate the source depth. A method for source depth estimation and qualitative binary source depth discrimination using the 0th‐order sound pressure, as well as the 1st‐ and 2nd‐order sound intensities, was proposed. The numerical simulation results confirmed the ability of the proposed method to approximate the source depth and discriminate between surface and submerged sources without requiring long‐term tracking or knowledge of the ocean environment.

Abstract In the pursuit of enhancing the efficiency of solar cells, accurate estimation of unspecified parameters in the solar photovoltaic (PV) cell model is imperative. An advanced salp swarm algorithm called the Super‐Evolutionary Nelder‐Mead Salp Swarm Algorithm (SENMSSA) is proposed to achieve this objective. The proposed SENMSSA addresses the limitations of SSA by incorporating a super‐evolutionary mechanism based on a Gaussian‐Cauchy mutation and a vertical and horizontal crossover mechanism. This mechanism enhances both the global optimization capabilities and the local search performance and convergence speed of the algorithm. It enables a secondary refinement of the global optimum, unlocking untapped potential in the solution space near the global optimum and elevating the algorithm's precision and exploitation capabilities to higher levels. The Nelder‐Mead simplex method is further introduced to enhance local search capabilities and convergence accuracy. The Nelder‐Mead simplex method is a versatile optimization algorithm that improves local search by iteratively adjusting a geometric shape (simplex) of points. It operates without needing derivatives, making it suitable for non‐smooth or complex objective functions. To assess the efficacy of SENMSSA, a comparative analysis is conducted against other available algorithms, namely SSA, IWOA, SCADE, LWOA, CBA, and RCBA, using the CEC2014 benchmark function set. Subsequently, the algorithm was employed to determine the unknown PV parameters under fixed conditions for three different diode models. Additionally, SENMSSA is utilized to estimate PV parameters for three commercially available PV models (ST40, SM55, KC200GT) under varying conditions. The experimental results indicate that the SENMSSA proposed in this study displays a remarkably competitive performance in all test cases compared to other algorithms. As such, we consider that the SENMSSA algorithm constitutes a reliable and efficient solution for the challenge of PV parameter estimation.

Preservation conditions are key to enriching shallow shale gas. Therefore, the veins of two typical wells in the Shixi syncline in northern Guizhou as research objects. Based on core observation, vein thin-section observation, cathodoluminescence, calcite in situ U-Pb dating, fluid inclusion microthermometry, Raman spectrum shift, single well basin simulation, and C-O isotope geochemical analysis, the researchers clarified the characteristics of the veins and the differences in paleofluid activity, as well as their significance for shale gas preservation. The results showed that: 1) a small number of high-angle fractures had developed mainly in the Shixi syncline in northern Guizhou. The width of viens is small and filled primarily with early calcite-quartz and late calcite. The inclusions were mainly methane and brine. The proportion of brine inclusions in the SD1 well was greater than that in the SX1 well. The SD1 well has experienced more intense second-stage uplift and denudation, and the consequent gas loss is serious. 2) The results of the C-O isotope analysis showed that most of the vein-forming fluids were derived from marine carbonate rocks. The O3b had obvious negative deviations of δ13C and δ18O, which were modified by exogenous or deep hydrothermal fluid. The C-O isotope difference between the vein bodies and the surrounding rock of the SX1 well was small, and the preservation conditions were better. 3) The difference in gas content in the Shixi syncline depends on the degree of damage to gas reservoir preservation conditions caused by burial depth and other factors. Shixi syncline is a wide and gentle syncline with central retention enrichment mode. Therefore, clarifying the development of shale veins, the characteristics of paleofluid activity, and their significance for shale gas preservation can lay a foundation for studying the enrichment mechanism of shallow shale gas and thus guide further exploration and development.

Abstract Nutrient-sensing pathways undergo deregulation in aged animals, exerting a pivotal role in regulating the cell cycle and subsequent stem cell division. Nevertheless, their precise functions in governing pluripotent stem cell differentiation remain largely elusive. Here, we uncovered a significant alteration in the cellular constituents of the intestinal epithelium in aged humans and mice. Employing Drosophila midgut and mouse organoid culture models, we made an observation regarding the altered trajectory of differentiation in intestinal stem cells (ISC) during overnutrition or aging, which stems from the erroneous activation of the insulin receptor signaling pathway. Through genetic analyses, we ascertained that the nutrient-sensing pathway regulated the direction of ISC differentiation by modulating the maturation of endosomes and SOX21A transcription factor. This study elucidates a nutrient-sensing pathway-mediated mechanism underlying stem cell differentiation, offering insights into the etiology of stem cell dysfunction in aged animals, including humans.

Abstract Evanescent Bloch waves are eigensolutions of spatially periodic problems for complex-valued wavenumbers at finite frequencies, corresponding to solutions that oscillate in time and space and that exponentially decay in space. Such evanescent waves are ubiquitous in optics, plasmonics, elasticity, and acoustics. In the limit of zero frequency, the wave “freezes” in time. We introduce frozen evanescent waves as the eigensolutions of the Bloch periodic problem at zero eigenfrequency. Elastic waves, i.e., phonons, in metamaterials serve as an example. We show that, in the complex plane, the Cauchy-Riemann equations for analytical functions connect the minima of the phonon band structure to frozen evanescent phonons. Their exponential decay length becomes unusually large if a minimum in the band structure tends to zero and thereby approaches a soft mode. This connection between unusual static and dynamic behaviors allows to engineer large characteristic decay lengths in static elasticity. For finite-size samples, the static solutions for given boundary conditions are linear combinations of frozen evanescent phonons, leading to interference effects. Theory and experiment are in excellent agreement. Anomalous behavior includes the violation of Saint Venant’s principle, which means that large decay-length frozen evanescent phonons can potentially be applied in terms of remote mechanical sensing.

Abstract Vector beams have attracted widespread attention because of their unique optical properties; in particular, their combination with tight focusing can produce many interesting phenomena. The rise of 3D printing technology provides more possibilities for exploration. In this work, a cascading method involving a metamaterial and a metalens is used to generate a tightly focused field of vector beams in the terahertz band, which is prepared via 3D printing. As a proof-of-concept demonstration, a series of metamaterial modules capable of generating states of different orbital angular momentum are proposed by cascading with a metalens. The experimental results are in good agreement with the simulation results, fully verifying the feasibility of the scheme. The proposed design and fabrication strategy provides a new idea for the tight focusing of terahertz vector beams.

Abstract Electrocatalytic CO2 reduction technology offers an effective way to convert CO2 into valuable chemicals and fuels, presenting a sustainable solution for carbon emissions. Current electrocatalytic CO2 reduction technologies encounter significant issues such as salt precipitation and hydrogen evolution, which prevent energy conversion efficiency, selectivity, current density, and stability from simultaneously meeting industrial standards. In recent years, researchers have discovered that increasing the CO2 pressure on the gas supply could enhance the coverage of the catalyst and activate more CO2 reduction reaction sites on the catalyst surface, which provides a practical and effective approach for optimizing the energy conversion and mass transfer. In this review, we provide a comprehensive review of the development history and current status of high-pressure CO2 electrocatalytic reduction technology, focusing on its reaction devices, catalytic performance, and reaction mechanisms. Furthermore, we summarize and offer insights into the most promising research avenues to propel the field forward.

Abstract In engineering applications, optimal parameter design is crucial. While Slime Mould Algorithm (SMA) excels in parameter discovery under constrained conditions, it faces challenges in achieving global convergence and avoiding local opsecttimal traps in complex tasks. This paper introduces an enhanced variant of SMA, termed CCHSMA, which integrates a Chaotic Local Search (CLS) mechanism to improve initial population diversity and combines Covariance Matrix Adaptation (CMA) and Harris Hawks Optimization (HHO) strategies to enhance global search efficiency. CCHSMA aims to improve search quality and reduce the likelihood of getting trapped in local optima. We evaluated CCHSMA's effectiveness by benchmarking it against the standard SMA and its variants using 30 CEC2017 test functions, and compared its performance with seven notable meta-heuristic algorithms and ten advanced swarm intelligence variants. The experimental results demonstrate that CCHSMA outperforms the other algorithms tested on the benchmark functions. To further validate its practical utility, CCHSMA's performance was also benchmarked against leading algorithms in real-world engineering applications. This paper uses detailed statistical methods, including the Wilcoxon signed-rank test and the Friedman test, to validate the comparative results. Our findings show that CCHSMA outperforms other algorithms in solving complex engineering optimization problems such as tension/compression spring design, pressure vessel design, and three-bar truss design, proving to be a robust tool for complex engineering optimization. Its enhanced initial population diversity and improved global search efficiency are essential for effectively addressing diverse engineering challenges.

Abstract Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.

Abstract Background Arecae Semen is a traditional herbal medicine widely used in the medical service and food industry, but in recent years, the carcinogenesis of edible Arecae Semen chewing has aroused comprehensive attention, therefore it is necessary to evaluate its medicinal properties. Increasing evidence has shown that Arecae Semen Compounds (ASC) possess antidepressant ability. This study aimed to evaluate the effectiveness and safety of ASC in the treatment of depression. Methods We retrieved articles in eight databases from their inception to May 2024. Randomized controlled trials (RCTs) comparing the effects of ASC alone or combined with routine treatment in patients with depression were identified. The Cochrane risk of bias (ROB) tool (ROB 2) was used for assessing the ROB in the included trials. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of the evidence for the review outcomes. The outcomes included Hamilton depression rating scale (HAMD) scores, depression-related symptoms, serum dopamine levels, and adverse events. Stata 14.0 was used for data analysis calculating standardized mean difference (SMD) for continuous outcomes and relative risk (RR) for binary outcomes, both with 95% confidence intervals (CI). Results Nine RCTs involving 787 patients were included in this review. ASC lowered HAMD scores (SMD − 3.43, 95% CI − 5.24 to − 1.61; I 2 = 95.2%, P

Abstract Introduction This study analyzed and discussed the characteristics of peripheral blood lymphocytes (PBLs) in patients with endometrial carcinoma (EC) to explore the PBLs’ clinical application value. Methods This single-center case‒control study analyzed the clinical data of patients with EC and uterine fibroids who underwent surgery at the First Affiliated Hospital of Chongqing Medical University between October 2018 and October 2023 retrospectively. The Center for Clinical Molecular Medical Detection of our hospital performed PBLs detection using flow cytometry, and recorded the detection results in the electronic medical records system. Between-group and subgroup comparisons of PBLs in patients with EC were analyzed using t-test or Mann–Whitney U test. The effect of surgery on PBLs in patients with EC was assessed using a paired t-test or the Wilcoxon signed rank test. Results The immune function of patients with EC was significantly lower than that of healthy people (P < 0.05) and those with benign uterine diseases (P < 0.05) and was related to body mass index (BMI), hypertension, diabetes, and blood lipids (P < 0.05). In patients with EC, the PBLs counts decreased significantly after surgery (P < 0.05) and more kinds of lymphocytes were affected in the laparoscopic surgery group than in the open surgery group. Conclusions With the decrease of PBLs counts, the immune status of patients with EC is impaired. Metabolic syndrome (Mets), including obesity, hypertension, diabetes, and high blood lipids, also affects the immune function of patients with EC. And for EC patients, the effect of laparoscopic surgery is greater than that of open surgery. PBLs has the potential to be one of indicator during the diagnosis and treatment of EC. Trial registration This study was retrospectively registered by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (approval number K2023-578).

Abstract Background Gastric cancer (GC) is the third leading cause of cancer-related deaths globally. Despite advancements in treatment, the overall 5-year survival rate remains below 30%, particularly in advanced stages. Copper metabolism, vital for various cellular processes, has been linked to cancer progression, but its role in GC, especially at the single-cell level, is not well understood. Objective This study aims to investigate copper metabolism in GC by integrating single-cell RNA sequencing (scRNA-seq) data and developing a prognostic model based on copper metabolism-related gene (CMRG) expression. The study explores how copper metabolism affects the tumor microenvironment and identifies potential therapeutic targets. Methods scRNA-seq data from gastric cancer and normal tissues were analyzed using the Seurat package. Principal Component Analysis (PCA) and Uniform Manifold Approximation and Projection (UMAP) were used for dimensionality reduction and clustering. Non-negative matrix factorization (NMF) was employed for T cell subpopulation analysis. A high-dimensional weighted gene co-expression network analysis (HdWGCNA) identified key molecular features. LASSO regression and Random Survival Forest (RSF) techniques were used to create and validate a prognostic model. Survival analysis, immune microenvironment assessment, and drug sensitivity analysis were conducted. Results Sixteen cell clusters and nine distinct cell types were identified, with T cells showing significant roles in cell communication. The NMF analysis of CD8 +T cells revealed five copper metabolism-related subtypes. The prognostic model based on nine CMRGs indicated significant survival differences between high- and low-risk groups. High-risk patients showed shorter survival times, increased immune cell infiltration, and altered immune responses. Drug sensitivity analysis suggested higher efficacy of certain drugs in high-CMRG patients.

Abstract The redox state of a planetary mantle affects its thermal evolution. The redox evolution of lunar mantle, however, remains unclear due to limited oxygen fugacity (fO2) constraints from young lunar samples. Here, we report vanadium (V) oxybarometers on olivine and spinel conducted on 27 Chang’e-5 basalt fragments from 2.0 billion years ago. These fragments yield an average fO2 of ΔIW -0.84 ± 0.65 (2σ), which closely aligns with the Apollo samples from 3.6–3.0 billion years ago. This temporal uniformity indicates the lunar mantle remained reduced. This observation reveals that the processes responsible for oxidizing mantles of Earth and Mars either did not occur or had negligible oxidizing effects on the Moon. The long-term reduced mantle may lead to a distinctive volatile degassing pathway for the Moon. It could also make the lunar mantle more difficult to melt, preventing internal heat dissipation and consequently resulting in a slow cooling rate.

Abstract Background The BEAN1 gene, primarily studied in neurodegenerative diseases, has been scarcely studied in the context of cancers. Our research examines BEAN1 expression specifically in rectal adenocarcinoma (READ) and its association with prognosis, immune evasion, and chemotherapy resistance. Methods Data from TCGA and GEO were analyzed to assess BEAN1 levels across various cancer types, with particular emphasis on READ. Functional enrichment, immune infiltration, and treatment response analyses were conducted, followed by validation using patient tissue samples. Results READ tissues exhibited a marked increase in BEAN1 expression compared to normal tissues. Elevated BEAN1 levels were associated with reduced overall survival and increased immune suppression, characterized by elevated M2 macrophage infiltration and reduced CD8+ T cell presence. BEAN1 expression was also linked to higher immune checkpoint genes expression and resistance to immune checkpoint inhibitors and 5-fluorouracil. Conclusion This research offers initial evidence that BEAN1 is linked to unfavorable prognosis, immune escape, and resistance to chemotherapy in READ. BEAN1 appears to be a promising new biomarker and potential therapeutic target, warranting further investigation into its potential clinical applications in improving treatment outcomes for READ patients.

Abstract The poor prognosis of hepatocellular carcinoma (HCC) is still an urgent challenge to be solved worldwide. Hence, assembling drugs and targeted short peptides together to construct a novel medicine delivery strategy is crucial for targeted and synergy therapy of HCC. Herein, a high-efficiency nanomedicine delivery strategy has been constructed by combining graphdiyne oxide (GDYO) as a drug-loaded platform, specific peptide (SP94-PEG) as a spear to target HCC cells, sorafenib, doxorubicin-Fe2+ (DOX-Fe2+), and siRNA (SLC7A11-i) as weapons to exert a three-path synergistic attack against HCC cells. In this work, SP94-PEG and GDYO form nanosheets with HCC-targeting properties, the chemotherapeutic drug DOX linked to ferrous ions increases the free iron pool in HCC cells and synergizes with sorafenib to induce cell ferroptosis. As a key gene of ferroptosis, interference with the expression of SLC7A11 makes the ferroptosis effect in HCC cells easier, stronger, and more durable. Through gene interference, drug synergy, and short peptide targeting, the toxic side effects of chemotherapy drugs are reduced. The multifunctional nanomedicine GDYO@SP94/DOX-Fe2+/sorafenib/SLC7A11-i (MNMG) possesses the advantages of strong targeting, good stability, the ability to continuously induce tumor cell ferroptosis and has potential clinical application value, which is different from traditional drugs.

The study investigated the effects of violin note B7 (Violin), double bass note E1 (Bass) and Mozart’s Sonata for Two Pianos in D Major, K. 448 (Mozart), on laying hens in terms of the production performance, egg quality and physiological characteristics. One hundred and sixty 600-day-old laying hens (ISA Brown) were randomly categorised into four groups with four replicates (10 hens/ replicate), and exposed to specific sound frequency for 12 weeks. The results indicated that Violin group presented significantly higher thick albumin height, Haugh unit and yolk index compared to the control group (p

The increasingly frequent storms pose significant threats to the sustainable development of coastal regions, particularly in densely populated and economically vibrant areas. Comprehending the dynamics and intricate mechanisms underlying runoff generation is crucial in the context of climate change and anthropogenic interference. Based on hydro-meteorological and land-use data from 1980 to 2018, this study investigates the runoff variation and its driving factors in the Coastal Chinese Mainland (CCM). The aims of this study are to reveal the temporal and spatial trends of runoff yield, to clarify the sensitivity of runoff in coastal cities to the integrated and individual parameters of climate change and anthropogenic interference, including precipitation (P), potential evapotranspiration (E0), and land cover factor (n), and to support the establishment of spatially tailored adaptation strategies. The results show that: (1) runoff has generally increased over the study period, particularly in regions such as the Yangtze River Delta, Shandong, and Guangxi, while it has decreased in western Liaoning and eastern Guangdong; (2) in the northern CCM with larger aridity index, the land cover factor plays a dominant role in runoff production, while in the wetter southern CCM, precipitation is more influential, and potential evapotranspiration mainly hinders runoff generation all over CCM; (3) urban expansion tends to negatively impact n, while the loss of grasslands and shrinkage of croplands tend to undermine the value of n. To facilitate the achievement of sustainable development goals in the CCM, it is imperative to introduce a more comprehensive and theoretical framework that encompasses the natural, technical, and social dimensions of human-water systems into traditional flood regulation and water resource management. This framework should promote interdisciplinary collaboration from an integrated perspective, to bridge the administrative and watershed boundaries, to effectively address the complex challenges posed by climate change and anthropogenic activities on runoff and water resources in coastal regions, and to enhance the realization of local sustainable development goals (UN SDGs).

Item response theory (IRT) is a modern psychometric framework for estimating respondents’ latent traits (e.g., ability, attitude, and personality) based on their responses to a set of questions in psychological tests. The current study adopted an item response tree (IRTree) method, which combines the tree model with IRT models for handling the sequential process of responding to a test item, to score individual moral inclination for the CNI test—a broadly adopted model for examining humans’ moral decision-making with three parameters generated: sensitivity to moral norms, sensitivity to consequences, and inaction preference. Compared to previous models for the CNI test, the resulting EIRTree-CNI Model is able to generate individual scores without increasing the number of items (thus, less subject fatigue or compromised response quality) or employing a post hoc approach that is deemed statistically suboptimal. The model fits the data well, and the subsequent test also supported the concurrent validity and the predictive validity of the model. Limitations are discussed further.

Based on the principle of super-symmetric lens with quadratic phase gradient transformation, combined with the principle of digital coding of metasurface, we propose a wide-angle coded metalens for focusing control in two-dimensional space. This metalens achieves focus shift in the x-direction by changing the oblique incidence angle of the incident wave, and focus control in the y-direction by combining with the convolution principle of the digitally coded metasurface to achieve flexible control of light focusing in the two-dimensional plane. The metasurface unit is mainly composed of three-layer of metal structure and two layers of medium, and the transmission phase is obtained by changing the middle layer of metal structure, which in turn obtains the required phase distribution of the metalens. The design of the metalens realizes the function of the lens with a large viewing angle at the x-polarized incidence, and realizes two-dimensional focus control. Experimentally, we prepared the designed coding metalens and tested the focus control function of the wide-angle coding metalens. The experimental results are in good agreement with the design results.

Abstract The dose–response of intravenous lidocaine in preventing postoperative vomiting (POV) in children remains unclear. This study investigated whether intravenous lidocaine dose-dependently decreased POV risk within 24 h postoperatively in children undergoing tonsillectomy (with or without adenoidectomy) without severe complications. Patients aged 3–12 years (American Society of Anesthesiologists grade I–II) scheduled for elective tonsillectomy (with or without adenoidectomy) were enroled from December 2021 to March 2022. They were randomly grouped according to the lidocaine dose (A [0 mg kg−1], B [1 mg kg−1], C [1.5 mg kg−1], and D [2 mg kg−1]) and were administered the same induction protocol (sufentanil, propofol, and suxamethonium chloride). Anaesthesia was maintained with sevoflurane. The incidence of POV within 24 h postoperatively was 46, 40, 36, and 20% in groups A, B, C, and D, respectively, with significant differences between groups D and A. Postoperative analgesic rescues in groups A, B, C, and D were 62, 36, 34, and 16%, respectively, with significant differences between groups D and B, C and A, and D and A. No severe adverse events were reported. Intravenous lidocaine has a dose-dependent effect on reducing the risk of POV in children undergoing tonsillectomy (with or without adenoidectomy) without serious adverse events. Trial registration: Chinese Clinical Trial Registry, ChiCTR2100053006.

The shale of the Lower Cambrian Niutitang Formation in the Guizhou region has undergone complex diagenesis and has developed different types of pore textures, which affect the occurrence status of shale. In the present study, we applied scanning electron microscopy (SEM) and an isotherm analysis of low-temperature nitrogen gas adsorption to shale core samples drawn from the Niutitang Formation in the Guizhou region to quantify the shale pore development characteristics. In addition, we conducted a shale geochemical analysis in light of the main controlling factors for pore development. The results indicate that the shale pores and fractures of the Niutitang Formation can be divided into three types: organic pores, inorganic pores, and micro fractures. The organic pores are mainly distributed in the organic matter between inorganic mineral particles, with small pore diameters, which are characterized by inkpot, elliptic, and beaded shapes. The inorganic pores are mainly composed of narrow slit intragranular pores and intergranular pores. The micro fractures develop parallel plates with four-side openings and splint plates. The pores of the shale are mainly mesopores (53%), followed by micropores and macropores, with pore diameter distributions ranging mainly from 1 to 50 nm. The specific surface area is mainly provided by nanoscale pores with average diameters of less than 4 nm. Therefore, the smaller pore makes a greater contribution to the specific surface area, while the specific surface area increases with an increase in the total pore volume. The study further indicates that organic carbon content is the most important internal factor for shale pore development, especially in terms of the control of volume and the specific surface area of micropores. Moreover, quartz content has a certain effect on shale pores; the pore volume and specific surface area increase with increasing quartz content, but the control effect is not obvious. The effect of clay minerals on shale pores is negligible. The type of organic matter is also an important factor in controlling the developmental difference of shale pores, and a high degree of thermal evolution is not conducive to organic pore development. It was therefore concluded that intergranular pores and microfractures, mainly mesopores, are the main reservoir space and migration channels of Niutitang shale in the study area. The organic carbon content, mineral components, organic matter type, and degree of thermal evolution jointly control the development of shale pores, among which the organic carbon content is the most important influencing factor.

Abstract Objective This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance. Methods A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data. Results In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model. Conclusion Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD.

Abstract Third-generation EGFR tyrosine kinase inhibitors (TKIs), exemplified by osimertinib, have demonstrated promising clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Our previous work has identified ASK120067 as a novel third-generation EGFR TKI with remarkable antitumor effects that has undergone New Drug Application (NDA) submission in China. Despite substantial progress, acquired resistance to EGFR-TKIs remains a significant challenge, impeding the long-term effectiveness of therapeutic approaches. In this study, we conducted a comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found a notable upregulation of branched-chain amino acid transaminase 1 (BCAT1) expression in both osimertinib- and ASK120067-resistant tumors compared with the parental TKI-sensitive NSCLC tumors. Genetic depletion or pharmacological inhibition of BCAT1 impaired the growth of resistant cells and partially re-sensitized tumor cells to EGFR TKIs. Mechanistically, upregulated BCAT1 in resistant cells reprogrammed branched-chain amino acid (BCAA) metabolism and promoted alpha ketoglutarate (α-KG)-dependent demethylation of lysine 27 on histone H3 (H3K27) and subsequent transcriptional derepression of glycolysis-related genes, thereby enhancing glycolysis and promoting tumor progression. Moreover, we identified WQQ-345 as a novel BCAT1 inhibitor exhibiting antitumor activity both in vitro and in vivo against TKI-resistant lung cancer with high BCAT1 expression. In summary, our study highlighted the crucial role of BCAT1 in mediating resistance to third-generation EGFR-TKIs through epigenetic activation of glycolysis in NSCLC, thereby supporting BCAT1 as a promising therapeutic target for the treatment of TKI-resistant NSCLC.

Abstract On a global note, oral health plays a critical role in improving the overall human health. In this vein, dental-related issues with dentin exposure often facilitate the risk of developing various oral-related diseases in gums and teeth. Several oral-based ailments include gums-associated (gingivitis or periodontitis), tooth-based (dental caries, root infection, enamel erosion, and edentulous or total tooth loss), as well as miscellaneous diseases in the buccal or oral cavity (bad breath, mouth sores, and oral cancer). Although established conventional treatment modalities have been available to improve oral health, these therapeutic options suffer from several limitations, such as fail to eradicate bacterial biofilms, deprived regeneration of dental pulp cells, and poor remineralization of teeth, resulting in dental emergencies. To this end, the advent of nanotechnology has resulted in the development of various innovative nanoarchitectured composites from diverse sources. This review presents a comprehensive overview of different nanoarchitectured composites for improving overall oral health. Initially, we emphasize various oral-related diseases, providing detailed pathological circumstances and their effects on human health along with deficiencies of the conventional therapeutic modalities. Further, the importance of various nanostructured components is emphasized, highlighting their predominant actions in solving crucial dental issues, such as anti-bacterial, remineralization, and tissue regeneration abilities. In addition to an emphasis on the synthesis of different nanostructures, various nano-therapeutic solutions from diverse sources are discussed, including natural (plant, animal, and marine)-based components and other synthetic (organic- and inorganic-) architectures, as well as their composites for improving oral health. Finally, we summarize the article with an interesting outlook on overcoming the challenges of translating these innovative platforms to clinics. Graphical abstract

In order to improve the yield of jackfruit peel pectin (JFPP) and obtain high-purity pectin with good functional properties, this study optimized the extraction process of pectin by ultrasound-assisted cellulase enzyme method through response surface experiments. The extracted pectin was preliminarily purified, including degreasing, deproteinization, decolorization, and dialysis concentration process. The purified pectin was then enzymatically esterified and modified by de-esterification to obtain de-esterified jackfruit peel pectin (DE-JFPP), and a comparative analysis was conducted on the basic composition, molecular weight, monosaccharide composition, functional group characteristics, thermal stability, and microstructure of the pectin before and after modification. The results showed that the optimal conditions for the extraction process were enzyme dosage of 0.7%, the enzymatic hydrolysis temperature of 30.4 ℃, and the pH of 4.6. It was observed that the yield of JFPP was 15.26%±0.07% under the specified conditions. The galacturonic acid content in the modified pectin increased from 79.10% to 83.24%, with a decrease in total sugar content from 43.42% to 41.90%, a decrease in esterification degree from 84.25% to 32.36%, and a decrease in weight-average molecular weight from 29.24 ku to 28.49 ku. Both JFPP and DE-JFPP contained eleven monosaccharides and belonged to the RG-I pectin with a decrease in the degree of branching in DE-JFPP. Fourier transform infrared (FTIR) spectroscopy demonstrated that both the pectin before and after modification had characteristic absorption peaks of pectin, and the peak area corresponding to the esterified carboxyl acid group decreased after modification. The JFPP and DE-JFPP demonstrated high thermal stability, with solubilization temperatures of 160.22 ℃ and 123.28 ℃, and degradation temperatures of 255.11 ℃ and 230.56 ℃, respectively. Scanning electron micrographs (SEM) showed that JFPP had a smooth surface and a compact structure, and DE-JFPP had a rough surface and a loose structure. This study optimized the extraction process of jackfruit peel pectin, improving its yield. Results demonstrated that the esterified pectin had favorable physicochemical properties and microstructure, meeting requirements for gel carrier systems in various fields and expanding the utilization space of jackfruit peel pectin.

Abstract The precise forecasting of air quality is of great significance as an integral component of early warning systems. This remains a formidable challenge owing to the limited information of emission source and the considerable uncertainties inherent in dynamic processes. To improve the accuracy of air quality forecasting, this work proposes a new spatiotemporal hybrid deep learning model based on variational mode decomposition (VMD), graph attention networks (GAT) and bi-directional long short-term memory (BiLSTM), referred to as VMD–GAT–BiLSTM, for air quality forecasting. The proposed model initially employ a VMD to decompose original PM2.5 data into a series of relatively stable sub-sequences, thus reducing the influence of unknown factors on model prediction capabilities. For each sub-sequence, a GAT is then designed to explore deep spatial relationships among different monitoring stations. Next, a BiLSTM is utilized to learn the temporal features of each decomposed sub-sequence. Finally, the forecasting results of each decomposed sub-sequence are aggregated and summed as the final air quality prediction results. Experiment results on the collected Beijing air quality dataset show that the proposed model presents superior performance to other used methods on both short-term and long-term air quality forecasting tasks.

Abstract The global scenario on PVC plasticizer is experiencing a drastic change from petroleum-based, toxic di-(2-ethylhexyl) phthalate (DEHP) toward renewable, non-toxic bio-alternatives. However, replacing diisodecyl phthalate (DIDP), a DEHP analogue specifically intended for plasticizing PVC automotive upholstery, with bio-alternative remains a challenge as few bio-plasticizer volatilizes from PVC as slowly as DIDP, a crucial aspect compulsorily required by automotive industry. Here, we demonstrate that covalently attaching two short esters at the α-position of all components of a traditional epoxidized fatty acid methyl ester via a two-step, hydrogen-to-ester nucleophilic substitution in a one-pot procedure yields an epoxidized fatty acid tri-ester bio-plasticizer with remarkably suppressed volatilization from PVC, and hence an extremely low fogging value comparable to DIDP. With this strategy in hand, DIDP, long deemed irreplaceable despite its toxicity and non-renewable nature, may ultimately be phased out. Graphical Abstract

[Introduction] Aiming at the characteristics of offshore converter stations, the design scheme for wireless communication system of offshore converter station is proposed. [Method] By analyzing the characteristics and current application of offshore wireless communication technology and considering the requirements of equipment operation, station warning and personnel activities of offshore converter stations, the configuration scheme for the wireless communication system of offshore converter stations was proposed. [Result] Through the NAVTEX system, the requirement to receive weather and safety information is realized. Through the radar optoelectronic system and VHF ship to ship communication system, the requirement for vessel caution and expulsion is realized. Through UHF cluster intercom system, WiFi and mobile communication system, the daily communication requirement of personnel is realized. Through the lifeboat emergency communication system, microwave transmission system and satellite communication system, the requirement of personnel emergency avoidance is realized. [Conclusion] Therefore, the system can realize the basic communication requirements during the daily operation and maintenance of offshore converter stations, ensure the safety of equipment and personnel, and provide guidance for the design of wireless communication systems for offshore converter stations.

Abstract Background In contemporary times, increased prevalence of Helicobacter pylori (H. pylori) infection and elevated dyslipidemia levels present substantial public health challenges. However, the relationship between H. pylori and dyslipidemia remains inconclusive. No studies have yet conducted a population-based classification to investigate the impact of H. pylori infection on dyslipidemia in individuals with diabetes. Methods A retrospective cohort study was carried out on a total of 60,535 individuals who underwent health check-ups at the Health Examination Center in Taizhou Hospital from 2017 to 2022. Physical measurements, hematological markers and detection of H. pylori were gathered from all patients. The study population was further stratified into diabetic and non-diabetic groups for analysis. Results H. pylori infection was found to be an autonomous risk factor for dyslipidemia based on the results of multivariate logistic regression analysis (OR = 1.13, 95% CI: 1.03–1.24). However, no notable effect on dyslipidemia in the non-diabetic group was observed. Furthermore, at the follow-up, the group with persistent negative showed a significantly lower incidence ratio of dyslipidemia compared to the group with persistent infection (P = 0.006). The persistent negative group exhibited a significantly higher rate of improvement in dyslipidemia compared to the new infection group (P = 0.038). Conclusions In the diabetic population, the presence of H. pylori infection heightens the propensity for developing dyslipidemia. Therefore, the implementation of efficient eradication strategies for H. pylori infection could potentially lead to a decrease in the occurrence of dyslipidemia among individuals with diabetes.

Abstract Background This study aimed to assess the impact of coronavirus disease 2019 (COVID-19) on hospital service utilization and revenue in Chinese tertiary hospitals and develop an optimal pandemic control strategy (OPCS) for the peak period of the Omicron wave. Methods Retrospective data from three Chinese tertiary hospitals (provincial, city, and county level) were analyzed for three phases: pre-outbreak (Jan-Apr 2019), outbreak (Jan-Apr 2020), and post-outbreak (Jan-Apr 2021). OPCS was developed under the guidance of the China government pandemic control policy during post-break phase of COVID-19. A decision-tree model was constructed to compare OPCS to strict pandemic control strategy during outbreak phase for the hospital service utilization and hospital revenue in a provincial tertiary hospital during the Omicron wave. Results Outpatient, emergency room (ER) visits, hospitalizations, and intensive care admissions dropped by 33.8–53.4% during the outbreak, with the provincial hospital being the most affected. Hospital revenue also declined, especially for the provincial hospital (40.1%). Post-outbreak, most services recovered, but ER visits remained lower (11.6% decrease for provincial hospital, 46.5% for county hospital). Total income and expenditure decreased, with the provincial hospital experiencing the most significant revenue reduction (45.7%). OPCS showed greater utilization of medical services (31.6 times more outpatient visits; 1.7 times more inpatient days; 3.4% more surgery volume) and higher revenue (¥220.8 million more) compared to the strict pandemic control strategy. Conclusions COVID-19 measures were associated with less hospital service utilization and revenue in Chinese tertiary hospitals. The developed OPCS in Chinese tertiary hospitals, focusing on isolating infected inpatients but not shutting down the hospital facilities exposed to virus, could be effective in optimizing hospital service utilization and hospital revenue during the Omicron wave.

Abstract The paradigm of lunar crust formation has been widely applied to other terrestrial bodies, but the nature of early crust building on the Moon remains enigmatic. Here we report non-Apollo-like highland clasts from the Chang’e-5 mission and find high-alumina melts enclosed in a noritic anorthosite. Geochemistry and phase equilibria modeling suggest that the melt is compositionally parental to lunar magnesian-suite rocks, and was sourced from a plagioclase-bearing, orthopyroxene-dominated upper mantle ( ~ 4.5 kbar and 1225°C). It was formed as a direct consequence of upper mantle melting at the onset of gravitational instability. We propose a continuous early crust formation on the Moon, started from multiple anorthositic cumulate flotations, to upper mantle melting caused by small-scale, in-situ overturn, and eventually ended up by decompression melting of lower mantle cumulates following large-scale, global overturn.

Highlights Novel laser-induced transfer method for fabricating glucose sensors from recycled e-waste copper, offering a sustainable and cost-effective solution. Unique heterogeneous Cu x O nano-skeletons derived from discarded printed circuit boards exhibiting exceptional glucose-sensing performance (sensitivity: 9.893 mA mM−1 cm−2, detection limit: 0.34 μM). Miniaturized glucose detection device, optimized for scalability and portability, revolutionizing diabetes management and patient care.

Abstract As countries attach importance to environmental protection, clean energy has become a hot topic. Among them, solar energy, as one of the efficient and easily accessible clean energy sources, has received widespread attention. An essential component in converting solar energy into electricity are solar cells. However, a major optimization difficulty remains in precisely and effectively calculating the parameters of photovoltaic (PV) models. In this regard, this study introduces an improved rime optimization algorithm (RIME), namely ERINMRIME, which integrates the Nelder-Mead simplex (NMs) with the environment random interaction (ERI) strategy. In the later phases of ERINMRIME, the ERI strategy serves as a complementary mechanism for augmenting the solution space exploration ability of the agent. By facilitating external interactions, this method improves the algorithm’s efficacy in conducting a global search by keeping it from becoming stuck in local optima. Moreover, by incorporating NMs, ERINMRIME enhances its ability to do local searches, leading to improved space exploration. To evaluate ERINMRIME's optimization performance on PV models, this study conducted experiments on four different models: the single diode model (SDM), the double diode model (DDM), the three-diode model (TDM), and the photovoltaic (PV) module model. The experimental results show that ERINMRIME reduces root mean square error for SDM, DDM, TDM, and PV module models by 46.23%, 59.32%, 61.49%, and 23.95%, respectively, compared with the original RIME. Furthermore, this study compared ERINMRIME with nine improved classical algorithms. The results show that ERINMRIME is a remarkable competitor. Ultimately, this study evaluated the performance of ERINMRIME across three distinct commercial PV models, while considering varying irradiation and temperature conditions. The performance of ERINMRIME is superior to existing similar algorithms in different irradiation and temperature conditions. Therefore, ERINMRIME is an algorithm with great potential in identifying and recognizing unknown parameters of PV models.

Abstract Urbanization is one of the milestones in the development of human society. Many regions in the southern parts of ‘the old world’ demonstrating an early emergence of agriculture also witnessed the flourishing of some of the earliest cities. Recent, yet still sparse, archaeological evidence appears to indicate a relatively later time for early urbanism in central Eurasia. However, given its vital geographic location and cultural nexus between East and West, more attention should be paid to the sedentary communities and their cities in oases amid the vast droughty desert, particularly in light of the rapidly increasing number of publications on early pastoralism and related communication routes along mountain chains and rivers. This study reveals the trajectory of urbanization and its role in the establishment of an exchange network in Xinjiang’s oasis region via reconstruction of the chronological sequence of the local societal history of the Baiyang River Basin along the southern piedmont of the Eastern Tianshan Mountains. A thorough archaeological investigation and refined radiocarbon dating programme was carried out and coupled with information from historical documentation within a Bayesian statistical framework. The results indicate three pulses of local urbanization during: the Early Iron Age, Tang–Yuan period, and Qing Dynasty, respectively. Combining this with evidence from other parts of Xinjiang, we re-evaluate the role of oasis urbanism in the promotion of trans-regional exchange.

In 2020 and 2021, peach fruit with natural disease and decay were collected from orchards in Zhejiang Province. Then the fungal pathogens were isolated from the diseased spots and identified by morphological characteristics, molecular biological identification (rDNA-ITS sequence analysis) and pathogenicity detection. The antifungal effect of cinnamon essential oil on the fungal pathogens in vitro and in vivo were also investigated. The results showed that two fungal pathogens with strong pathogenicity were isolated, and identified as Monilinia fructicola and Rhizopus stolonifer, which caused brown rot and soft rot, respectively. Cinnamon essential oil inhibited the growth of M. fructicola and R. stolonifer, and the minimum inhibitory concentrations were 0.4 and 0.8 mL/L, respectively. M. fructicola was more sensitive to cinnamon essential oil. Cinnamon essential oil fumigation could reduce the disease incidence and lesion diameter of brown rot and soft rot of peach fruit caused by these two fungal pathogens. Therefore, cinnamon essential oil could be used as a natural fungicide to control fungal diseases of peach fruit.

Abstract Background Glycerophospholipids (GPLs) are essential for cell membrane structure and function. Sphingomyelin and its metabolites regulate cell growth, apoptosis, and stress responses. This study aimed to investigate lipid metabolism in patients experiencing sudden sensorineural hearing loss across all frequencies (AF-SSNHL). Methods The study included 60 patients diagnosed with unilateral AF-SSNHL, among whom 30 patients had a level of hearing improvement ≥ 15 dB after 6 months of follow-up. A propensity score-matched (2:1) control group was used. Liquid chromatography‒mass spectrometry based untargeted lipidomics analysis combined with multivariate statistics was performed to investigate the lipids change. The “lipidome” R package and weighted gene co-expression network analysis (WGCNA) were utilised to assess the lipids’ structural features and the association between lipids and hearing. Results Lipidomics successfully differentiated the AF-SSNHL group from the control group, identifying 17 risk factors, mainly including phosphatidylcholine (PC), phosphatidylethanolamine (PE), and related metabolites. The ratios of lysophosphatidylcholine/PC, lysophosphatidylethanolamine/PE, and lysodimethylphosphatidylethanolamine/PE were upregulated, while some glycerophospholipid (GPL)-plasmalogens were downregulated in the AF-SSNHL group, indicating abnormal metabolism of GPLs. Trihexosylceramide (d34:1), PE (18:1e_22:5), and sphingomyelin (d40:3) were significantly different between responders and nonresponders, and positively correlated with hearing improvement. Additionally, the results of the WGCNA also suggested that partial GPL-plasmalogens were positively associated with hearing improvement. Conclusion AF-SSNHL patients exhibited abnormally high blood lipids and pronounced GPLs metabolic abnormalities. Sphingolipids and GPL-plasmalogens had an association with the level of hearing improvement. By understanding the lipid changes, clinicians may be able to predict the prognosis of hearing recovery and personalize treatment approaches.

Abstract The current clinical application of glaucoma drainage devices is made of non-degradable materials. These non-degradable drainage devices often trigger inflammatory responses and scar proliferation, possibly leading to surgical failure. We developed a biodegradable material hydroxyapatite-coated magnesium (HA-Mg) as a glaucoma drainage device. Twelve New Zealand white rabbits were randomly assigned to three groups: HA-Mg drainage plate group (6 right eyes), trabeculectomy group (6 right eyes), and control group (12 left eyes). Results showed that all HA-Mg drainage plates were completely degraded ~4 months postoperatively. At the 5th month postoperatively, there was no statistical difference in the corneal endothelium density between the HA-Mg drainage plate group and the control group (p = 0.857). The intraocular pressure (IOP) level in the HA-Mg drainage plate implantation group was lower than in the other two groups. The trypan blue dye still drained from the anterior chamber to the subconjunctiva 5 months after HA-Mg drainage plate implantation. HE staining revealed the scleral linear aqueous humor drainage channel and anterior synechia were observed after drainage plate completely degraded, with no obvious infiltration with the inflammatory cells. This study showed the safety and efficacy of HA-Mg glaucoma drainage plate in controlling IOP after implantation into the anterior chamber of rabbit eyes. Graphical abstract We developed a biodegradable material hydroxyapatite-coated magnesium (HA-Mg) as a glaucoma drainage device. This study evaluated the safety and efficacy of HA-Mg glaucoma drainage plate in controlling intraocular pressure after implantation into the anterior chamber of rabbit eyes.

Abstract Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from proteins and nucleic acids. Leveraging their exceptional biological properties and modifiable characteristics, phages emerge as innovative, safe, and efficient delivery vectors. The potential drawbacks associated with conventional nanocarriers in the realms of drug and gene delivery include a lack of cell-specific targeting, cytotoxicity, and diminished in vivo transfection efficiency. In contrast, engineered phages, when employed as cargo delivery vectors, hold the promise to surmount these limitations and attain enhanced delivery efficacy. This review comprehensively outlines current strategies for the engineering of phages, delineates the principal types of phages utilized as nanocarriers in drug and gene delivery, and explores the application of phage-based delivery systems in disease therapy. Additionally, an incisive analysis is provided, critically examining the challenges confronted by phage-based delivery systems within the domain of nanotechnology. The primary objective of this article is to furnish a theoretical reference that contributes to the reasoned design and development of potent phage-based delivery systems. Graphical abstract

Abstract Background Patient-reported outcome (PRO) is a distinct and indispensable dimension of clinical characteristics and recent advances have made remote PRO measurement possible. Sex difference in PRO of Parkinson’s disease (PD) is hardly extensively researched. Methods A smartphone-based self-management platform, offering remote PRO measurement for PD patients, has been developed. A total of 1828 PD patients, including 1001 male patients and 827 female patients, were enrolled and completed their PRO submission through this platform. Results Sex differences in PROs have been identified. The female group had a significantly lower height, weight, and body mass index (BMI) than the male group (P

Abstract Direct hydrogen production from inexhaustible seawater using abundant offshore wind power offers a promising pathway for achieving a sustainable energy industry and fuel economy. Various direct seawater electrolysis methods have been demonstrated to be effective at the laboratory scale. However, larger-scale in situ demonstrations that are completely free of corrosion and side reactions in fluctuating oceans are lacking. Here, fluctuating conditions of the ocean were considered for the first time, and seawater electrolysis in wave motion environment was achieved. We present the successful scaling of a floating seawater electrolysis system that employed wind power in Xinghua Bay and the integration of a 1.2 Nm3 h−1-scale pilot system. Stable electrolysis operation was achieved for over 240 h with an electrolytic energy consumption of 5 kWh Nm−3 H2 and a high purity (>99.9%) of hydrogen under fluctuating ocean conditions (0~0.9 m wave height, 0~15 m s−1 wind speed), which is comparable to that during onshore water electrolysis. The concentration of impurity ions in the electrolyte was low and stable over a long period of time under complex and changing scenarios. We identified the technological challenges and performances of the key system components and examined the future outlook for this emerging technology.

Abstract Background Human toxocariasis is a neglected parasitic disease characterised by the syndromes visceral, cerebral, and ocular larva migrans. This disease is caused by the migrating larvae of Toxocara roundworms from dogs and cats, affecting 1.4 billion people globally. Via extracellular vesicles (EVs), microRNAs have been demonstrated to play roles in host–parasite interactions and proposed as circulating biomarkers for the diagnosis and follow-up of parasitic diseases. Methods Small RNA-seq was conducted to identify miRNAs in the infective larvae of T. canis and plasma EV-containing preparations of infected BALB/c mice. Differential expression analysis and target prediction were performed to indicate miRNAs involved in host–parasite interactions and miRNAs associated with visceral and/or cerebral larva migrans in the infected mice. Quantitative real-time polymerase chain reaction (PCR) was used to amplify circulating miRNAs from the infected mice. Results This study reports host and parasite miRNAs in the plasma of BALB/c mice with visceral and cerebral larva migrans and demonstrates the alterations of these miRNAs during the migration of larvae from the livers through the lungs and to the brains of infected mice. After filtering unspecific changes in an irrelevant control, T. canis-derived miRNAs and T. canis infection-induced differential miRNAs are predicted to modulate genes consistently involved in mitogen-activated protein kinase (MAPK) signalling and pathways regulating axon guidance and pluripotency of stem in the infected mice with visceral and cerebral larva migrans. For these plasma circulating miRNAs predicted to be involved in host-parasite crosstalk, two murine miRNAs (miR-26b-5p and miR-122-5p) are experimentally verified to be responsive to larva migrans and represent circulating biomarker candidates for visceral and cerebral toxocariasis in BALB/c mice. Conclusions Our findings provide novel insights into the crosstalk of T. canis and the mammalian host via plasma circulating miRNAs, and prime agents and indicators for visceral and cerebral larva migrans. A deep understanding of these aspects will underpin the diagnosis and control of toxocariasis in humans and animals. Graphical Abstract

Abstract Image segmentation techniques play a vital role in aiding COVID-19 diagnosis. Multi-threshold image segmentation methods are favored for their computational simplicity and operational efficiency. Existing threshold selection techniques in multi-threshold image segmentation, such as Kapur based on exhaustive enumeration, often hamper efficiency and accuracy. The whale optimization algorithm (WOA) has shown promise in addressing this challenge, but issues persist, including poor stability, low efficiency, and accuracy in COVID-19 threshold image segmentation. To tackle these issues, we introduce a Latin hypercube sampling initialization-based multi-strategy enhanced WOA (CAGWOA). It incorporates a COS sampling initialization strategy (COSI), an adaptive global search approach (GS), and an all-dimensional neighborhood mechanism (ADN). COSI leverages probability density functions created from Latin hypercube sampling, ensuring even solution space coverage to improve the stability of the segmentation model. GS widens the exploration scope to combat stagnation during iterations and improve segmentation efficiency. ADN refines convergence accuracy around optimal individuals to improve segmentation accuracy. CAGWOA's performance is validated through experiments on various benchmark function test sets. Furthermore, we apply CAGWOA alongside similar methods in a multi-threshold image segmentation model for comparative experiments on lung X-ray images of infected patients. The results demonstrate CAGWOA's superiority, including better image detail preservation, clear segmentation boundaries, and adaptability across different threshold levels.

Abstract Synovial Sarcomas (SS) are characterized by the presence of the SS18::SSX fusion gene, which protein product induce chromatin changes through remodeling of the BAF complex. To elucidate the genomic events that drive phenotypic diversity in SS, we performed RNA and targeted DNA sequencing on 91 tumors from 55 patients. Our results were verified by proteomic analysis, public gene expression cohorts and single‐cell RNA sequencing. Transcriptome profiling identified three distinct SS subtypes resembling the known histological subtypes: SS subtype I and was characterized by hyperproliferation, evasion of immune detection and a poor prognosis. SS subtype II and was dominated by a vascular‐stromal component and had a significantly better outcome. SS Subtype III was characterized by biphasic differentiation, increased genomic complexity and immune suppression mediated by checkpoint inhibition, and poor prognosis despite good responses to neoadjuvant therapy. Chromosomal abnormalities were an independent significant risk factor for metastasis. KRT8 was identified as a key component for epithelial differentiation in biphasic tumors, potentially controlled by OVOL1 regulation. Our findings explain the histological grounds for SS classification and indicate that a significantly larger proportion of patients have high risk tumors (corresponding to SS subtype I) than previously believed.

Macrophage polarization facilitates the inflammatory response and intensified fibrosis in the silicosis microenvironment by a mechanism related to macrophage pyroptosis, although the upstream target remains poorly defined. Currently, there are few reports on the development of drugs that alleviate macrophage polarization by dampening pyroptosis. The present study aims to explore the mechanics of silica mediating macrophage polarization and to investigate whether quercetin (Que) can depolarize macrophages with this mechanism. Silica processing led to prominent M1 polarization of macrophages. Additionally, significant macrophage polarization could be detected in the lung tissue of mice with airway-perfused silica. Further investigation turned out that pronounced mitochondria damage, mtDNA cytoplasmic ectomy, and pyroptosis occurred in response to silica. Nevertheless, Que treatment could effectively attenuate silica-induced mitochondria damage and pyroptosis as demonstrated in vitro and in vivo. Further exploration presented Que could bind to TOM70 and restore silica-induced mitochondrial damage. More importantly, the M1 polarization of macrophage was depressed with the co-treatment of Que and silica, wherein the inflammatory response and pulmonary fibrosis were also mitigated without obvious damage to vital organs. In conclusion, these findings proved that silica leads to mitochondrial damage, thereby evoking pyroptosis and promoting macrophage M1 polarization. Que could bind to TOM70 and restore its function, suppressing mitochondrial damage and pyroptosis, and depolarizing macrophages to reduce fibrosis, which provides a promising strategy for silicosis treatment in the future.

Water-saving irrigation (WI) is a crucial agricultural management with the benefits to save irrigation water, reduce energy consumption, and suppress methane emissions from paddy lands. Classifying WI practices from traditional flooding irrigation (FI) is a key component in detecting the rice irrigation status, which is significant to estimate the total agriculture-associated greenhouse gas emissions. In this study, we developed an automatic method to map irrigation regimes across Chinese paddy lands. First, we used seven variables related with irrigation facility or vegetation cover as proxy to generate representative WI and FI samples. Besides, we composited 123 features of optical bands and synthetic aperture radar from MODIS and Sentinel-1 data. Then, we trained a random forest model for each province with these samples. Finally, we applied the trained model to generate maps of WI/FI practices at 500 m resolution. Comparisons of the resultant maps with census data indicated highly accurate estimations of the WI area at a city- or province-level, with a R2 higher than 0.92. The overall accuracy of the classification was approximately 0.73, as validated through ground truth samples. Additionally, we also conducted a data quality analysis and confirmed the classification results were reliable in main rice production area of China. With the push towards carbon neutrality goals and the increasing demand for clean management practices, we developed and demonstrated an advanced method to produce near real-time maps of irrigation regimes and provide crucial data support for agricultural emissions reduction and irrigation management decisions.

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder affecting millions of people worldwide, with no effective treatment currently available. In recent decades, various traditional Chinese medicines (TCMs) and their active ingredients have shown the potential to attenuate the pathogenesis of AD in cellular and animal models. However, the effects of TCM formulas, which are typically administered in practice, have been less studied. This study aims to investigate the therapeutic effects of several formulas consisting of 4 components herbal components: catalpol, puerarin, gastrodin, and borneol, on streptozotocin (STZ)-induced AD models in cells and rats. The new object recognition (NOR), elevated plus maze (EMP), and Morris water maze (MWM) tests were used to evaluate the cognitive functions of rats. Golgi staining, Haematoxylin and Eosin (HE) staining, and Nissl staining analyses were employed assess the physiology of hippocampal tissues. Gene expression profiles were analyzed used transcriptomics and reverse transcription quantitative polymerase chain reaction analysis, while protein expression levels were determined using immunoblotting, immunohistochemical, and immunofluorescence. The production of cytokines was evaluated with enzyme-linked immunosorbent assay. The results demonstrated that the combined administration of these 4 components (CPGB) had superior mitigating effects on AD cell model, as evidenced by the reduced pro-inflammatory cytokine production and decreased deposition of Aβ protein. Further in vivo and in vitro experiments confirmed that varying doses of CPGB formula effectively ameliorated STZ-induced cognitive deficits, as shown by NOR, MWM, and EMP tests, as well as pathological changes in hippocampal tissues and a 3-dimensional brain neurovascular unit (3D-NVU) model, including decreased deposition of Aβ protein and formation of plaques. Transcriptome sequencing and analysis identified 35 genes with significantly altered expression levels due to STZ and CPGB treatment in hippocampal tissues, which were enriched in the Tlr4/Myd88/NF-κB signaling pathway. Interference with this pathway significantly influenced the therapeutic effects of CPGB in the 3D-NVU model. Collectively, these findings suggest that the combined administration of catalpol, puerarin, gastrodin, and borneol offers superior therapeutic effects on AD by modulating the Tlr4/Myd88/NF-κB signaling pathway. This study strengthens the theoretical foundation for using TCMs to treat AD, proving new insights and references for alleviating and treating AD.

BackgroundLimitations of conventional treatment methods for sleep disorders have driven the use and development of complementary and alternative therapies such as acupuncture. However, despite the surge in related studies, there is still a lack of visual analysis and detailed elaboration regarding the current status, international collaborations, and research hotspots of acupuncture for sleep disorders.MethodsWe conducted a bibliometric analysis of publications on acupuncture for sleep disorders using the Web of Science Core Collection database from 2004 to 2023. We utilized the R package “bibliometrix” to count publications and citations, VOSviewer to create an inter-institutional referencing network, and CiteSpace to identify references and keywords with the highest citation bursts. Additionally, we employed a bibliometric online analysis platform designed for analyzing national partnerships.ResultsA total of 432 pertinent papers were retrieved, with China being the most prolific contributor, accounting for 61.6% of the publications, followed by the United States and South Korea. Despite China’s high output, its average article citation rate and proportion of international collaborations were notably lower than those of the United States. Key research institutions such as the University of Hong Kong, Shanghai University of Traditional Chinese Medicine, Memorial Sloan Kettering Cancer Center, and Guangzhou University of Chinese Medicine have played significant roles in this field. Among authors, Ka-Fai Chung from the University of Hong Kong stood out as the most productive. In terms of journals, MEDICINE was the most active, while SLEEP was considered the most authoritative. The clinical effects of acupuncture for insomnia have garnered significant attention in recent years, with electroacupuncture emerging as the prevailing technique for addressing sleep disorders.ConclusionThis bibliometric study effectively outlines the basic framework of knowledge surrounding acupuncture for sleep disorders over the past two decades, covering publications, countries, institutions, authors, and sources. It highlights promising clinical effects and underlying mechanisms of acupuncture, particularly for secondary insomnia and specific sleep disorders like restless legs syndrome. Moving forward, the focus and challenge for future research lie in the development of standardized study protocols and harmonization of efficacy assessment metrics.

BackgroundCardiovascular disease significantly impacts human health. The development of carotid plaques elevates the risk of cardiovascular disease, while the influence of Helicobacter pylori (H. pylori) on carotid plaques remains a subject of debate. This study aimed to investigate the association between H. pylori infection and carotid plaque using a cohort study.MethodsThe study included individuals who underwent multiple physical examinations at the Health Examination Center of Taizhou Hospital. The relationship between H. pylori and carotid plaque was explored using multifactorial logistic regression analysis. Participants were categorized into groups based on their H. pylori infection status at the initial and final examinations, comprising persistent infection, persistent negative, new infection, and eradication infection, to analyze variations in carotid plaque prevalence among these groups.ResultsIn both univariate and multifactorial regression analyses, H. pylori was identified as a risk factor for carotid plaque development. Moreover, when compared to the persistent negative group, both the new infection and persistent infection groups showed a notable increase in the risk of carotid plaque. Additionally, individuals in the persistent infection group exhibited higher blood pressure and blood glucose levels than those in the persistent negative group. Likewise, there was a discrepancy in the impact of insulin resistance on carotid plaque between the H. pylori positive and negative groups.ConclusionH. pylori is a risk factor for carotid plaque, with a long-term infection associated with an increased risk of carotid plaque formation. In addition, H. pylori promoting carotid plaque formation may be related to blood pressure, blood glucose, and insulin resistance.