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AIM: To evaluate the efficacy and safety of the intravitreal dexamethasone implant in naive and refractory patients with diabetic macular edema (DME). METHODS: PubMed, Embase, Web of Science, and Medline databases were searched. The main outcomes were best-corrected visual acuity (BCVA) and central retinal thickness (CRT). The secondary outcomes included mean number of injections, intraoperative or postoperative complications including intraocular pressure (IOP) elevation and cataract. RESULTS: Ten comparative studies involving a total of 1000 DME eyes including 402 naive eyes and 598 refractory eyes were selected. The postoperative BCVA in the naive group was significantly better than in the refractory group [mean difference (MD) -0.11, 95% confidence interval (CI) -0.17 to -0.05, P=0.0003; MD 8.69, 95%CI 5.08 to 12.30, P

Goji (Lycium barbarum L.) leaves flavonoid microcapsules (M-LBLF) were prepared using gelatin and carboxymethyl cellulose sodium (CMC) as wall materials, and the stability and biological activities were investigated. The preparation process of M-LBLF was optimized through response surface methodology. The stability of the product was detected using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis and in vitro simulated digestion. The biological activity of the product was evaluated through free radical scavenging and enzyme activity inhibition experiments. Results showed that, the optimal process conditions for M-LBLF were a core to wall ratio of 1:3.86, a wall material concentration of 1.15%, a stirring temperature of 45 ℃, and an embedding rate of 84.21%. SEM observation showed that most of the surface of the microcapsule particles was smooth, the structure of the capsule wall remained intact, and there were no signs of rupture on the wall material. FT-IR spectra showed a shift in C=O at 1594 cm−1 in Lycium barbarum leaves flavonoids (LBLF), suggesting an electrostatic interaction between LBLF and CMC. XRD spectra showed that due to microencapsulation, the amorphous structure of the product was partially transformed into a crystalline state, resulting in slight changes in the diffraction peak intensity of M-LBLF and LBLF. Thermogravimetric analysis found that microencapsulation improved the high-temperature decomposition, playing a protective role for LBLF. In vitro simulated digestion and antioxidant activity experiments showed that microencapsulation improved the stability of LBLF and retained good antioxidant activity during digestion. In addition, the equations were fitted by multiple linear regression to obtain the semi-inhibitory mass concentration (IC50) of the microcapsules against pancreatic lipase (2.2004±0.03 mg/mL) and against α-amylase (2.188±0.02 mg/mL), suggesting that M-LBLF was able to inhibit both pancreatic lipase activity and α-amylase activity, which suggested that it had the potential to regulate the glycolipid metabolism activity. This research would provide a foundation for improving the stability of flavonoids extracted from goji leaves and developing the related nutritional and health foods.

Abstract The underlying evolutionary mechanisms driving global expansions of pathogen strains are poorly understood. Vibrio parahaemolyticus is one of only two marine pathogens where variants have emerged in distinct climates globally. The success of a Vibrio parahaemolyticus clone (VpST3) in Latin America- the first spread identified outside its endemic region of tropical Asia- provided an invaluable opportunity to investigate mechanisms of VpST3 expansion into a distinct marine climate. A global collection of VpST3 isolates and novel Latin American isolates were used for evolutionary population genomics, pangenome analysis and combined with oceanic climate data. We found a VpST3 population (LatAm-VpST3) introduced in Latin America well before the emergence of this clone in India, previously considered the onset of the VpST3 epidemic. LatAm-VpST3 underwent successful adaptation to local conditions over its evolutionary divergence from Asian VpST3 isolates, to become dominant in Latin America. Selection signatures were found in genes providing resilience to the distinct marine climate. Core genome mutations and accessory gene presences that promoted survival over long dispersals or increased environmental fitness were associated with environmental conditions. These results provide novel insights into the global expansion of this successful V. parahaemolyticus clone into regions with different climate scenarios.

Abstract Background Ectoine as an amino acid derivative is widely applied in many fields, such as the food industry, cosmetic manufacturing, biologics, and therapeutic agent. Large-scale production of ectoine is mainly restricted by the cost of fermentation substrates (e.g., carbon sources) and sterilization. Results In this study, Halomonas cupida J9 was shown to be capable of synthesizing ectoine using xylose as the sole carbon source. A pathway was proposed in H. cupida J9 that synergistically utilizes both WBG xylose metabolism and EMP glucose metabolism for the synthesis of ectoine. Transcriptome analysis indicated that expression of ectoine biosynthesis module was enhanced under salt stress. Ectoine production by H. cupida J9 was enhanced by improving the expression of ectoine biosynthesis module, increasing the intracellular supply of the precursor oxaloacetate, and utilizing urea as the nitrogen source. The constructed J9U-P8EC achieved a record ectoine production of 4.12 g/L after 60 h of xylose fermentation. Finally, unsterile production of ectoine by J9U-P8EC from either a glucose-xylose mixture or corn straw hydrolysate was demonstrated, with an output of 8.55 g/L and 1.30 g/L of ectoine, respectively. Conclusions This study created a promising H. cupida J9-based cell factory for low-cost production of ectoine. Our results highlight the potential of J9U-P8EC to utilize lignocellulose-rich agriculture waste for open production of ectoine.

Creep behavior is a very important attribute of shale and is crucial in the design of hydraulic fracturing schemes to ensure the long-term stable development of shale gas. However, how different shale minerals, organic matter, bedding planes, and pores affect the micro-creep behavior of Upper Ordovician Wufeng and Lower Silurian Longmaxi (WF–LMX) Formation shales is poorly understood. In this study, we employed a nanoindentation mechanical testing technique alongside rock mineralogical, major elemental, and pore analyses to investigate the creep behavior and influencing factors of WF–LMX shales at the microscale. The results show that (1) the creep displacement (Δh) and indentation creep parameter (CIT) are each positively correlated with clay, total pore volume, and clay + total organic carbon (TOC) contents but negatively correlated with the content of quartz, excess SiO2, and TOC. We found weak or no correlation between the occurrence of minor rock constituents, such as feldspar, carbonates, and pyrite, and the shale creep properties; (2) the creep parameters (Δh, CIT, and stress exponent (n)) exhibit anisotropy due to the layering of shale, with values 7.3%–24.2% higher in the plane perpendicular to bedding (X1) than those in the plane parallel to bedding (X3). The creep displacement exhibits negative correlations with Young's modulus, hardness, and stress exponent (n), especially for the X1 direction; (3) compared with those of China's Yanchang shale, the stress exponents of WF–LMX shale are relatively high (8.5–30), indicating that the average creep capacity of WF–LMX shale is relatively weak. Overall, nanoindentation technology has shown great potential in studying shale creep and provides quantitative data support for macroscopic shale creep research.

Listeria monocytogenes is capable of forming biofilms on the food contact surfaces, increasing the risk of food contamination by this pathogen. The disinfectant benzalkonium chloride (BC) is commonly used to control L. monocytogenes in the food industry. This study aimed to investigate effects of BC on L. monocytogenes biofilms. Biofilm biomass was measured by the microplate method with crystal violet staining. Results from the broth microdilution method showed that the minimum inhibitory concentration (MIC) of BC against L. monocytogenes 10403S was 8 μg.mL-1. Sub-MICs of BC inhibited the biofilm formation and lethal concentrations of BC removed mature biofilms of L. monocytogenes 10403S. The presence of BC reduced extracellular proteins and exopolysaccharides in biofilms. Additionally, upregulation of quorum sensing gene luxS and agrBDCA and downregulation of flagellum motility genes flaA, motA, and motB were observed in the presence of BC. The BC disinfectant has an excellent anti-biofilm activity against L. monocytogenes.

Abstract Federated learning (FL) enables users to train the global model cooperatively without exposing their private data across the engaged parties, which is widely used in privacy-sensitive business. However, during the life cycle of FL models, both adversaries’ attacks and ownership generalization threaten the FL models’ copyright and affect the models’ reliability. To address these problems, existing model watermarking techniques can be used to verify FL model’s ownership. However, due to the lack of credible binding from “model extracted watermarks” to “ownership verification”, it is difficult to form a closed-loop watermarking framework for copyright protection. Therefore, starting from the shortcomings of the current watermark verification scheme, this article proposed WFB, a blockchain-empowered watermarking framework for ownership verification of federated models. Firstly, we propose a improved watermark generation algorithm to solve the credibility issue of watermarks. Secondly, we propose a watermark embedding method in federated learning, while blockchain technology is used to ensure the credible storage of watermark information throughout the process. Thirdly, the credibility of ownership verification is improved because of the watermark authenticity. Experimental results demonstrate the fidelity, effectiveness and robustness of WFB, with other superiorities such as improving process security and traceability.

Abstract Background There is a contradiction in the use of microbiota-therapies, including probiotics, prebiotics, and synbiotics, to improve the condition of patients with nonalcoholic fatty liver disease (NAFLD). The aim of this review was to evaluate the effect of microbiota-therapy on liver injury, inflammation, and lipid levels in individuals with NAFLD. Methods Using Pubmed, Embase, Cochrane Library, and Web of Science databases were searched for articles on the use of prebiotic, probiotic, or synbiotic for the treatment of patients with NAFLD up to March 2024. Results Thirty-four studies involving 12,682 individuals were included. Meta-analysis indicated that probiotic, prebiotic, and synbiotic supplementation significantly improved liver injury (hepatic fibrosis, SMD = -0.31; 95% CI: -0.53, -0.09; aspartate aminotransferase, SMD = -0.35; 95% CI: -0.55, -0.15; alanine aminotransferase, SMD = -0.48; 95% CI: -0.71, -0.25; alkaline phosphatase, SMD = -0.81; 95% CI: -1.55, -0.08), lipid profiles (triglycerides, SMD = -0.22; 95% CI: -0.43, -0.02), and inflammatory factors (high-density lipoprotein, SMD = -0.47; 95% CI: -0.88, -0.06; tumour necrosis factor alpha, SMD = -0.86 95% CI: -1.56, -0.56). Conclusion Overall, supplementation with probiotic, prebiotic, or synbiotic had a positive effect on reducing liver enzymes, lipid profiles, and inflammatory cytokines in patients with NAFLD.

Abstract Low-dimensional multiferroics, which simultaneously possess at least two primary ferroic order parameters, hold great promise for post-Moore electronic devices. However, intrinsic one-dimensional (1D) multiferroics with the coexistence of ferroelectricity and ferromagnetism are still yet to be realized, which will be not only crucial for exploring the interplay between low-dimensionality and ferroelectric/ferromagnetic ordering but also significant in rendering application approaches for high density information technologies. Here, we present a theoretical prediction of intrinsic multiferroicity in 1D molybdenum oxytrihalides nanowires, especially focusing on MoOBr3 nanowires which could be readily extracted from experimentally synthesized van der Waals MoOBr3 bulk materials. Due to the spatial inversion symmetry spontaneously broken by Mo atoms’ displacements, MoOBr3 nanowires exhibit 1D ferroelectricity with small coercive electric field and exceptional Curie temperature (~570 K). Additionally, MoOBr3 nanowires also possess 1D antiferroelectric metastable states. On the other hand, both ferroelectric and antiferroelectric MoOBr3 nanowires exhibit ferromagnetic ordering on account of the half-filled Mo-d yz orbitals, a moderate tensile strain (~5%) can greatly boost the spontaneous polarization (~40%) and a mild compress strain (~−2%) may readily switch the magnetic easy axis of ferroelectric MoOBr3 nanowires. Our work holds potential candidates for developing innovative devices that exploit intrinsic multiferroic properties, enabling advancements in novel electronic and spintronic applications.

This is an article in the field of metallurgical engineering. In order to explore the leaching mechanism of zinc oxide from zinc-containing dust by choline chloride and oxalic acid, the interaction of choline chloride and oxalic acid with 1∶1 and 1∶2 eutectic solvent on zinc oxide surface was simulated by means of quantum mechanics, and the simulation results were verified by experiments. The results show that the intermolecular hydrogen bond formed by choline chloride and oxalic acid plays an important role in the stability of eutectic solvent. Ch+ gains electrons, OA and Cl- lose electrons. ZnO(001) surface is the complete cleavage surface of zinc oxide, oxygen and zinc atoms form tetrahedral structure, oxygen atom is easy to gain electrons and zinc atom is easy to lose electrons during the reaction with the outside world. The zinc oxide loses electrons during the interaction between cholinergic chloride-oxalic acid and zinc oxide, and cholinergic chloride-oxalic acid gains electrons. The interaction energy △E=-819.6896Ha between ChCl-2OA and ZnO is small, indicating that zinc oxide is more likely to react with ChCl-2OA. The radial distribution function shows that the chemical adsorption is the main factor in the interaction between choline chloride and oxalic acid and zinc oxide, and the physical adsorption is the secondary factor. The contribution of Cl-Zn formed by chemical adsorption is greater than that of O-Zn. Through the pure mineral test, it can be verified that ChCl-2OA has a better leaching effect on zinc oxide, which verifies the accuracy of molecular simulation of the interaction mechanism between choline chloride and oxalic acid and zinc oxide, and provides a theoretical basis for the leaching of zinc-containing dust with eutectic solvent.

Abstract The establishment of an elastostatic stiffness model for over constrained parallel manipulators (PMs), particularly those with over constrained subclosed loops, poses a challenge while ensuring numerical stability. This study addresses this issue by proposing a systematic elastostatic stiffness model based on matrix structural analysis (MSA) and independent displacement coordinates (IDCs) extraction techniques. To begin, the closed-loop PM is transformed into an open-loop PM by eliminating constraints. A subassembly element is then introduced, which considers the flexibility of both rods and joints. This approach helps circumvent the numerical instability typically encountered with traditional constraint equations. The IDCs and analytical constraint equations of nodes constrained by various joints are summarized in the appendix, utilizing multipoint constraint theory and singularity analysis, all unified within a single coordinate frame. Subsequently, the open-loop mechanism is efficiently closed by referencing the constraint equations presented in the appendix, alongside its elastostatic model. The proposed method proves to be both modeling and computationally efficient due to the comprehensive summary of the constraint equations in the Appendix, eliminating the need for additional equations. An example utilizing an over constrained subclosed loops demonstrate the application of the proposed method. In conclusion, the model proposed in this study enriches the theory of elastostatic stiffness modeling of PMs and provides an effective solution for stiffness modeling challenges they present.

Abstract Gastric cancer represents a significant public health challenge, necessitating advancements in early diagnostic methodologies. This investigation employed attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy to conduct a multivariate analysis of human serum. The study encompassed the examination of blood samples from 96 individuals diagnosed with gastric cancer and 96 healthy volunteers. Principal component analysis (PCA) was utilized to interpret the infrared spectral data of the serum samples. Specific spectral bands exhibiting intensity variations between the two groups were identified. The infrared spectral ranges of 3500 ~ 3000 cm⁻1, 1700 ~ 1600 cm⁻1, and 1090 ~ 1070 cm⁻1 demonstrated significant diagnostic value for gastric cancer, likely attributable to differences in protein conformation and nucleic acids. By employing machine learning algorithms to differentiate between gastric cancer patients (n = 96) and healthy controls (n = 96), we achieved a sensitivity of up to 89.7% and a specificity of 87.2%. Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.901. These findings underscore the potential of our serum-based ATR-FTIR spectroscopy examination method as a straightforward, minimally invasive, and reliable diagnostic test for the detection of gastric cancer.

Abstract Spontaneous intracerebral hemorrhage (ICH) is a very serious kind of stroke. If the outcome of patients can be accurately assessed at the early stage of disease occurrence, it will be of great significance to the patients and clinical treatment. The present study was conducted to investigate whether non-contrast computer tomography (NCCT) models of hematoma and perihematomal tissues could improve the accuracy of short-term prognosis prediction in ICH patients with conservative treatment. In this retrospective analysis, a total of 166 ICH patients with conservative treatment during hospitalization were included. Patients were randomized into a training group (N = 132) and a validation group (N = 34) in a ratio of 8:2, and the functional outcome at 90 days after clinical treatment was assessed by the modified Rankin Scale (mRS). Radiomic features of hematoma and perihematomal tissues of 5 mm, 10 mm, 15 mm were extracted from NCCT images. Clinical factors were analyzed by univariate and multivariate logistic regression to identify independent predictive factors. In the validation group, the mean area under the ROC curve (AUC) of the hematoma was 0.830, the AUC of the perihematomal tissue within 5 mm, 10 mm, 15 mm was 0.792, 0.826, 0.774, respectively, and the AUC of the combined model of hematoma and perihematomal tissue within 10 mm was 0.795. The clinical-radiomics nomogram consisting of five independent predictors and radiomics score (Rad-score) of the hematoma model were used to assess 90-day functional outcome in ICH patients with conservative treatment. Our findings found that the hematoma model had better discriminative efficacy in evaluating the early prognosis of conservatively managed ICH patients. The visual clinical-radiomics nomogram provided a more intuitive individualized risk assessment for 90-day functional outcome in ICH patients with conservative treatment. The hematoma could remain the primary therapeutic target for conservatively managed ICH patients, emphasizing the need for future clinical focus on the biological significance of the hematoma itself.

The development of coal resources is currently focused on the clean and efficient use of coal. Coal processing and use generates sulfides, primarily hydrogen sulfide (H2S), which has a severe impact on production and environment. Adsorption desulfurization has become a popular desulfurization process in recent years because of its high desulfurization effectiveness, high precision, and ease of operation. With their large specific surface area and porosity, ease of modification and functionalization, the metal-organic frameworks(MOFs) have great potential in the field of gas adsorption. The introduction of polyethyleneimine (PEI), a polymer containing both primary, secondary and tertiary amines, has a strong affinity for H2S and undergoes reversible chemical reactions, and the introduction of PEI into MOFs is expected to further enhance the H2S adsorption performance. To this end, the PEI-loaded MIL-101(Cr), UiO-66, MOF-801, and ZIF-8 adsorbents were prepared by the impregnation method. The effect of carrier type and PEI loading on the H2S adsorption performance was investigated, and the recyclability of the adsorbents was examined. The results showed that the adsorption capacity of all carriers increased after PEI loading, with ZIF-8 increasing the most, which was attributed to the large specific surface area and pore volume of the ZIF-8 carrier itself, the maintenance of the crystal structure after loading, and the interaction between PEI and ZIF-8. The rest of the MOFs showed an unsatisfactory adsorption capacity after PEI loading due to their small specific surface area and pore volume or structural damage after PEI loading. The loading of PEI affected the pore structure and skeleton stability of ZIF-8. The highest ZIF-8 breakthrough capacity after 50% PEI loading was 56.3 mg/g, which is 55 times higher than the carrier itself. Regeneration cycling experiments showed that ZIF-8 loaded with PEI could only partially regenerate, that the adsorbent with low loadings had a better adsorption cycling performance than those with high loadings, and that the introduction of PEI made ZIF-8 more susceptible to the attack of H2S to form ZnS.

Abstract Profiling antibiotic resistance genes (ARGs) in the Yellow River of China’s Henan Province is essential for understanding the health risks of antibiotic resistance. The profiling of ARGs was investigated using high-throughput qPCR from water samples in seven representative regions of the Yellow River. The absolute and relative abundances of ARGs and moble genetic elements (MGEs) were higher in summer than in winter (ANOVA, p

Abstract Introduction It has been reported that non-intubated anesthesia can be used successfully in adult trachea reconstruction. Herein, our center reported a case of a child undergoing non-intubated trachea reconstruction for benign tracheal tumors. Case description In January 2023, it was decided to attempt tracheal resection and reconstruction (TRR) in an 8-year-old child with an inflammatory myofibroblastic tumor under non-intubated spontaneous breathing. After anesthesia induction, the laryngeal mask airway (LMA) was inserted. Thereafter, a bilateral superficial cervical plexus block was performed with 15 mL of 0.25% ropivacaine injected into each side. The patient was induced to resume spontaneous breathing by artificially assisted ventilation with an oxygen flow of 2 to 5 L/min and FiO2=1. After tracheotomy, the oxygen flow was increased to 15 L/min to improve the local oxygen flow to maintain the pulse oxygen saturation (SpO2) above 90% under spontaneous breathing. The patient had stable spontaneous breathing after tracheal anastomosis. The anastomosis was perfect without leakage. The LMA was removed and oxygen was given by the nasal catheter under light sedation at post anesthesia care unit (PACU). Conclusion Tracheal reconstruction under spontaneous breathing may be an alternative anesthesia method for upper tracheal surgery in children.

In this paper, the mechanical properties, work hardening characteristics and deformation mechanism of lean duplex stainless steel (LDSS) S32101 produced by direct cold rolling were studied under different temperature conditions. The yield strength (YS) and tensile strength (TS) of S32101 decreased with the increase of deformation temperature, while the elongation increased first and then decreased. The TS of S32101 at −70 °C was 1052.6 MPa, the elongation remained 57.2%, and the product of strength and elongation (PSE) was as high as 60.2 GPa·%, which was mainly due to the synergistic strengthening of transformation induced plasticity (TRIP) and twinning-induced plasticity (TWIP) effects in austenite at cryogenic temperatures. The efficiency of grain refinement at cryogenic temperature was improved by TRIP effect and deformation twins (DTs), indicating that it had the potential to be applied at low temperature (−70 ∼ −30°C). Moreover, the high density nanotwins and the strong interaction between the dislocation and nanotwin bundles also contributed to strain hardening at low temperatures and thus better comprehensive mechanical properties could be achieved.

Abstract Background The Aedes albopictus mosquito is of medical concern due to its ability to transmit viral diseases, such as dengue and chikungunya. Aedes albopictus originated in Asia and is now present on all continents, with the exception of Antarctica. In Mozambique, Ae. albopictus was first reported in 2015 within the capital city of Maputo, and by 2019, it had become established in the surrounding area. It was suspected that the mosquito population originated in Madagascar or islands of the Western Indian Ocean (IWIO). The aim of this study was to determine its origin. Given the risk of spreading insecticide resistance, we also examined relevant mutations in the voltage-sensitive sodium channel (VSSC). Methods Eggs of Ae. albopictus were collected in Matola-Rio, a municipality adjacent to Maputo, and reared to adults in the laboratory. Cytochrome c oxidase subunit I (COI) sequences and microsatellite loci were analyzed to estimate origins. The presence of knockdown resistance (kdr) mutations within domain II and III of the VSSC were examined using Sanger sequencing. Results The COI network analysis denied the hypothesis that the Ae. albopictus population originated in Madagascar or IWIO; rather both the COI network and microsatellites analyses showed that the population was genetically similar to those in continental Southeast Asia and Hangzhou, China. Sanger sequencing determined the presence of the F1534C knockdown mutation, which is widely distributed among Asian populations, with a high allele frequency (46%). Conclusions These results do not support the hypothesis that the Mozambique Ae. albopictus population originated in Madagascar or IWIO. Instead, they suggest that the origin is continental Southeast Asia or a coastal town in China. Graphical Abstract

Abstract Objectives To develop and validate a novel interpretable artificial intelligence (AI) model that integrates radiomic features, deep learning features, and imaging features at multiple semantic levels to predict the prognosis of intracerebral hemorrhage (ICH) patients at 6 months post-onset. Materials and methods Retrospectively enrolled 222 patients with ICH for Non-contrast Computed Tomography (NCCT) images and clinical data, who were divided into a training cohort (n = 186, medical center 1) and an external testing cohort (n = 36, medical center 2). Following image preprocessing, the entire hematoma region was segmented by two radiologists as the volume of interest (VOI). Pyradiomics algorithm library was utilized to extract 1762 radiomics features, while a deep convolutional neural network (EfficientnetV2-L) was employed to extract 1000 deep learning features. Additionally, radiologists evaluated imaging features. Based on the three different modalities of features mentioned above, the Random Forest (RF) model was trained, resulting in three models (Radiomics Model, Radiomics-Clinical Model, and DL-Radiomics-Clinical Model). The performance and clinical utility of the models were assessed using the Area Under the Receiver Operating Characteristic Curve (AUC), calibration curve, and Decision Curve Analysis (DCA), with AUC compared using the DeLong test. Furthermore, this study employs three methods, Shapley Additive Explanations (SHAP), Grad-CAM, and Guided Grad-CAM, to conduct a multidimensional interpretability analysis of model decisions. Results The Radiomics-Clinical Model and DL-Radiomics-Clinical Model exhibited relatively good predictive performance, with an AUC of 0.86 [95% Confidence Intervals (CI): 0.71, 0.95; P

Abstract Background Human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an inhibitory cell surface protein that functions through homophilic and heterophilic ligand binding. Its expression on immune cells in human tumors is poorly understood. Methods An antibody that distinguishes human CEACAM1 from other highly related CEACAM family members was labeled with 159Tb and inserted into a panel of antibodies that included specificity for programmed cell death protein 1 (PD1) and PD-L1, which are targets of immunotherapy, to gain a data-driven immune cell atlas using cytometry by time-of-flight (CyTOF). A detailed inventory of CEACAM1, PD1, and PD-L1 expression on immune cells in metastatic lesions to lymph node or soft tissues and peripheral blood samples from patients with treatment-naive and -resistant melanoma as well as peripheral blood samples from healthy controls was performed. Results CEACAM1 is absent or at low levels on healthy circulating immune cells but is increased on immune cells in peripheral blood and tumors of melanoma patients. The majority of circulating PD1-positive NK cells, innate T cells, B cells, monocytic cells, dendritic cells, and CD4+ T cells in the peripheral circulation of treatment-resistant disease co-express CEACAM1 and are demonstrable as discrete populations. CEACAM1 is present on distinct types of cells that are unique to the tumor microenvironment and exhibit expression levels that are highest in treatment resistance; this includes tumor-infiltrating CD8+ T cells. Conclusions To the best of our knowledge, this work represents the first comprehensive atlas of CEACAM1 expression on immune cells in a human tumor and reveals an important correlation with treatment-resistant disease. These studies suggest that agents targeting CEACAM1 may represent appropriate partners for PD1-related pathway therapies.

In this study, the high-temperature evolution of eutectic carbides in a medium-alloy steel was investigated as well as their precipitation mechanism. Results revealed that MC and M6C eutectic carbides in the steel appeared during the final solidification due to the segregation of Mo and V and the melt undercooling. These eutectic carbides consist of blocky shapes with varying orientations, and rod-like shapes with the same orientation. Further investigation was confirmed that the carbides (MC and M6C) exhibited an intergrowth behavior. The cooling rate had a direct influence on the secondary dendrite arm spacing (SDAS), which decreased from 180 to 130 μm as the rate ranged from 0.6 to 21.9 °C/min. After holding for 0, 25, 50, and 80 h, respectively, the volume percentage of eutectic carbides exhibited a significant decreasing trend from 2 to 0.2%. Additionaly, the carbides exhibited irregular morphology after holding for 0–50 h, respectively, and which was transformed into the rod-like shape with a small size distributed along the grain boundaries after holding for 80 h. This phenomenon was attributed to the mutual diffusion between Mo, V, and other alloying elements in the carbides and Fe element in the steel matrix.

To promote the construction industry and establish a green environment, the integration of sustainable building materials is urgently required. This study presents the influences of three materials (silica fume, fly ash, and recycled ceramic powder (RCP)) and different RCP dosages (0%, 10%, 20%, and 30%) on the mechanical properties and microstructure of concrete at different temperatures. The study presents the results of comprehensive flow tests, printability assessments, mechanical evaluations under different loading directions, high-temperature analyses, digital image correlation, X-ray powder diffraction and scanning electron microscopy. The experimental findings indicate the successful printing of all samples, with wall structure failure occurring only at a height of 730 mm. Furthermore, compared to those of other materials, the RCP displays a superior heat resistance, with a significant increase in compressive strength (28.9%) to 53.9 MPa at 300 °C. Additionally, the introduction of the RCP into 3D-printed concrete results in an anisotropic behaviour, with an initial enhancement in the mechanical strength, followed by attenuation as the RCP content increases. Microstructural analysis reveals enhanced interfacial adhesion with RCP addition, albeit accompanied by the emergence of numerous pores. The optimal mixture, which is designated as RCP-2-0-1 with 20% of the cement replaced by RCP, exhibits a significant anisotropic compressive strength (55.9 MPa) and an adequate anisotropic flexural strength (12.49 MPa) and impressive heat resistance (11.7% increase in compressive strength at 300 °C). This renders it a suitable sustainable impact-resistant thermal material for use in structural applications.

The coal chemical industry, as the main source of carbon emissions in China, will face great challenges under the constraints of the dual carbon goals. Coal derived gas deep desulfurization is an important component for highly efficient and clean utilization of coal, which is of great significance for carbon reduction. Zinc oxide is a commonly used adsorbent for desulfurization, but due to kinetic limitations, its room temperature desulfurization reactivity is very low, and this cannot meet the requirements of industrial application. Pore diffusion is a prerequisite for the reaction between ZnO and H2S, and is crucial for desulfurization performance. However, the influence of pore size, especially macropores, on the desulfurization performance and its mechanism have been rarely reported. For this reason, two ZnO/SiO2 adsorbents with mesopores and macropores in this study were prepared using a sol-gel method and a colloidal crystal template method, respectively, and the influence of macropores on their room temperature desulfurization performance was explored. It is found that although the introduction of macropores increases the specific surface area of the adsorbent, strengthens its surface alkalinity, improves the dispersion of ZnO, and increases the concentration of oxygen vacancies in the adsorbent, its introduction leads to a remarkable decrease in the desulfurization performance of adsorbent. The breakthrough sulfur capacity of mesoporous adsorbent is 151.9 mg/g, 2.3 times than that of macroporous adsorbent. This is because the macroporous structure is unstable and prone to collapse during the desulfurization process, which hinders the accessibility of reaction sites of ZnO; Secondly, the water vapor in the atmosphere is not conducive to the formation of a water film on the surface of macropores, thereby inhibiting the occurrence of desulfurization reactions. More importantly, the combustion of the template releases a large amount of heat during the preparation of macropores, which leads to a deep crosslinking of the SiO2 network and a decrease in the mesoporous pore size of adsorbent. The smaller mesoporous pore size results in an excessive amount of water physically adsorbed on its surface, inhibiting the reaction between ZnO and H2S.

This is an article in the field of metallurgical engineering. In order to better realize the leaching of zinc oxide from zinc-containing dust, Materials Studio software based on density functional theory was used to simulate and optimize the crystal structure of zinc oxide and the structure of three kinds of choline deep eutectic solvents, and the mutual adsorption model of the two was calculated. The calculated results show that the ZnO(001) plane is a complete cleavage plane, and the highest occupied state near the Fermi level shifts to the left, and the peak of the highest occupies state increases, and the p orbital of O and the d orbital of Zn are more active, which are the active sites of the ZnO(001) plane. Optimization of three choline hyper eutectic solvent shows that choline chloride forms multiple intermolecular hydrogen bonds with three different hydrogen bond donors centered on chlorine atom. The adsorption model of deep eutectic solvents and zinc oxide was calculated using Forcite module. The results shows that the interaction strength of zinc oxide with three choline deep eutectic solvent is Chcl-MA >Chcl-Urea>Chcl-Eg. The radial distribution function shows that malonic acid makes it easier for Cl in choline chloride to chemisorb with Zn. In the three kinds of hydrogen bond donors, the activity of oxygen atomic functional groups forming chemical bonds with Zn is C=O, N-O and C-O, indicating that C=O in malonic acid makes the combination of Chcl-MA and ZnO more stable. Results show that the leaching temperature of Chcl-MA is 70 ℃ and the liquid-solid ratio is 10∶1. Under the condition of leaching time of 1 h for 60 min, single mineral zinc oxide can be almost completely leached, and the leaching effect is far greater than that of Chcl-Urea and Chcl-Eg, thus proving the accuracy of molecular simulation and providing theoretical guidance for the leaching of zinc-containing dust in choline deep eutectic solvent.

Based on the waterflooding development in carbonate reservoirs in the Middle East, in order to solve the problem of the poor development effects caused by commingled injection and production, taking the thick bioclastic limestone reservoirs of Cretaceous in Iran-Iraq as an example, this paper proposes a balanced waterflooding development technology for thick and complex carbonate reservoirs. This technology includes the fine division of development units by concealed baffles and barriers, the combination of multi well type and multi well pattern, and the construction of balanced water injection and recovery system. Thick carbonate reservoirs in Iran-Iraq are characterized by extremely vertical heterogeneity, development of multi-genesis ultra-high permeability zones, and highly concealed baffles and barriers. Based on the technologies of identification, characterization, and sealing evaluation for concealed baffles and barriers, the balanced waterflooding development technology is proposed, and three types of balanced waterflooding development modes/techniques are formed, namely, conventional stratigraphic framework, fine stratigraphic framework, and deepened stratigraphic framework. Numerical simulations show that this technology is able to realize a fine and efficient waterflooding development to recover, in a balanced manner, the reserves of thick and complex carbonate reservoirs in Iran and Iraq. The proposed technology provides a reference for the development optimization of similar reservoirs.

Abstract Background Triple Negative Breast Cancer (TNBC) is a particular type of breast cancer with the highest mortality rate. Essential oils are concerned more and more as potential anti-cancer drugs. Methods TNBC cells were treated with different concentrations of navel orange peel essential oil (NOPEO), and then a variety of experiments were performed to investigate the changes in the growth and progression of TNBC cells. MTT assay was performed to detect the proliferation of TNBC cells. The changes of cell cycle and apoptosis were analyzed by FACS. In order to explored the migration of TNBC cells, scratch wound assay was carried out. Western blotting and qPCR were used to examine the expression of proteins and mRNA of related genes. Furthermore, RNA-seq was used to analyze the altered genes and explored the possible signal pathway. Results NOPEO demonstrated dose- and time-dependent suppression of TNBC cell growth. TNBC cells showed an increased percentage of G2/M-phase cells and the protein levels of CyclinB1 and CyclinD1 were decreased after NOPEO treatment. The apoptotic cells were increased in the NOPEO treated TNBC cells. The migration mobility was significantly inhibited by NOPEO. In total, 1376 genes were found to be up-regulated and 1335 genes were down-regulated after NOPEO treatment. According to KEGG and GO pathways, the differentially expressed genes were related to MAPK, Jak/stat and FoxQ signaling pathways. Conclusion This investigation explored the bio-activity and molecular mechanisms of NOPEO against TNBC cells. These results indicated that NOPEO could suppress TNBC growth and migration perhaps via the MAPK and Jak/stat signaling pathways, which may provide theoretical reference for anticancer drug development. NOPEO may be a potential natural product for the chemotherapeutic of TNBC.

Abstract Nonequilibrium dynamics governed by electron–phonon (e-ph) interactions plays a key role in electronic devices and spectroscopies and is central to understanding electronic excitations in materials. The real-time Boltzmann transport equation (rt-BTE) with collision processes computed from first principles can describe the coupled dynamics of electrons and atomic vibrations (phonons). Yet, a bottleneck of these simulations is the calculation of e–ph scattering integrals on dense momentum grids at each time step. Here we show a data-driven approach based on dynamic mode decomposition (DMD) that can accelerate the time propagation of the rt-BTE and identify dominant electronic processes. We apply this approach to two case studies, high-field charge transport and ultrafast excited electron relaxation. In both cases, simulating only a short time window of ~10% of the dynamics suffices to predict the dynamics from initial excitation to steady state using DMD extrapolation. Analysis of the momentum-space modes extracted from DMD sheds light on the microscopic mechanisms governing electron relaxation to a steady state or equilibrium. The combination of accuracy and efficiency makes our DMD-based method a valuable tool for investigating ultrafast dynamics in a wide range of materials.

Abstract Background Gastric precancerous lesions are a critical stage in the development of gastric cancer or gastric adenocarcinoma, and their outcome plays an important role in the malignant progression of gastric cancer. Coptidis Rhizoma has a good effect on Gastric precancerous lesions. However, the specific mechanisms of its action remain incompletely elucidated. Methods Network pharmacology and molecular docking techniques were used to explore the active ingredients and molecular mechanism of Coptidis Rhizoma in treating gastric precancerous lesions. The active compounds of Coptidis Rhizoma and their potential gastric precancerous lesions related targets were obtained from TCMSP, GeneCards, and OMIM databases. An interaction network based on protein–protein interactions (PPIs) was constructed to visualize the interactions between hub genes. Analysis of GO enrichment and KEGG pathway were conducted using the DAVID database. An investigation of interactions between active compounds and potential targets was carried out by molecular docking. Finally, animal experiments were conducted to verify the effect and mechanism of Coptidis Rhizoma in treating precancerous lesions of gastric cancer. Results A total of 11 active compounds and 95 anti-gastric precancerous lesions targets of Coptidis Rhizoma were screened for analysis. GO enrichment analysis showed that the mechanism of Coptidis Rhizoma acting on gastric precancerous lesions involves gene expression regulation and apoptosis regulation. KEGG pathway enrichment analysis showed that Coptidis Rhizoma against gastric precancerous lesions involving the AKT /HIF-1α/VEGF signalling pathway. Molecular docking simulations indicated potential interactions between these compounds and core targets involved in anti-gastric precancerous lesions activity. In addition, it was confirmed in vivo that Berberine and Coptidis Rhizoma may reverse atrophy and potential intestinal metaplasia by inhibiting the expression of p-AKT, HIFA, and VEGF. Conclusion Bioactive compounds in Coptidis Rhizoma have the potential to prevent atrophy and intestinal metaplasia. These compounds function by regulating the proteins implicated in AKT /HIF-1α/VEGF signalling pathways that are crucial in gastric epithelial cell differentiation, proliferation and maturation.

Abstract Due to the high degree of automation, automated guided vehicles (AGVs) have been widely used in many scenarios for transportation, and traditional computing power is stretched in large-scale AGV scheduling. In recent years, quantum computing has shown incomparable performance advantages in solving specific problems, especially Combinatorial optimization problem. In this paper, quantum computing technology is introduced into the study of the AGV scheduling problem. Additionally two types of quadratic unconstrained binary optimisation (QUBO) models suitable for different scheduling objectives are constructed, and the scheduling scheme is coded into the ground state of Hamiltonian operator, and the problem is solved by using optical coherent Ising machine (CIM). The experimental results show that compared with the traditional calculation method, the optical quantum computer can save 92% computation time on average. It has great application potential.

Abstract Although long-read sequencing enables the generation of complete genomes for unculturable microbes, its high cost limits the widespread adoption of long-read sequencing in large-scale metagenomic studies. An alternative method is to assemble short-reads with long-range connectivity, which can be a cost-effective way to generate high-quality microbial genomes. Here, we develop Pangaea, a bioinformatic approach designed to enhance metagenome assembly using short-reads with long-range connectivity. Pangaea leverages connectivity derived from physical barcodes of linked-reads or virtual barcodes by aligning short-reads to long-reads. Pangaea utilizes a deep learning-based read binning algorithm to assemble co-barcoded reads exhibiting similar sequence contexts and abundances, thereby improving the assembly of high- and medium-abundance microbial genomes. Pangaea also leverages a multi-thresholding algorithm strategy to refine assembly for low-abundance microbes. We benchmark Pangaea on linked-reads and a combination of short- and long-reads from simulation data, mock communities and human gut metagenomes. Pangaea achieves significantly higher contig continuity as well as more near-complete metagenome-assembled genomes (NCMAGs) than the existing assemblers. Pangaea also generates three complete and circular NCMAGs on the human gut microbiomes.

Abstract Inter-satellite link (ISL) plays an essential role in current and future Global Navigation Satellite System (GNSS). In this study, we investigate the impact of ISL observations on precise orbit determination for BeiDou-3 Navigation Satellite System (BDS-3) Medium Earth Orbit (MEO) satellites based on different Extended CODE Orbit Models (ECOM). Thanks to the better observation geometry of the Ka-band ISL data compared to the L-band data for BDS-3 MEO satellites, the ISL solution substantially reduces Orbit Boundary Discontinuity (OBD) errors, except for C30, which suffers from unstable Ka-band hardware delay. From the external quality analysis, ISL significantly enhances the reliability of the orbit of MEO satellites manufactured by the China Academy of Space Technology (CAST). The standard deviation (STD) of the satellite laser ranging (SLR) residuals is approximately 2.5 cm, and the root mean square (RMS) is reduced by 10–23% compared to L-band solutions. Besides, the Sun-elongation angle dependent systematic error in SLR residuals nearly vanishes based on the reduced 5-parameter ECOM (ECOM1) or extended 7-parameter ECOM (ECOM2) with ISL data. This is because the ISL reduces the correlation between state parameters and solar radiation pressure (SRP) parameters as well as those among SRP parameters, leading to a more accurate estimation of both orbit and SRP perturbations, particularly those along B direction. This confirms that the deficiency of the SRP models for BDS-3 CAST satellites can be compensated by using better observation geometry from ISL data. On the other hand, for the satellite manufactured by Shanghai Engineering Center for Microsatellites (SECM), the ISL allows for a more accurate estimation of the Bc 1 parameter in the ECOM1 model. This only reduces linear systematic error, possibly because the impact generated by the satellite bus cannot be entirely absorbed by the B-direction parameters.

Abstract Developing accurate wind speed forecasting methods is indispensable to integrating wind energy into smart grids. However, current state‐of‐the‐art wind speed forecasting methods are almost data‐driven deep learning models, which may incur potential adversarial cyberattacks. To this end, this paper proposes an adversarial false data injection attack tactic to investigate such a cyber threat. First, targeting the deep learning‐based short‐term wind speed forecasting model, an optimization model is constructed to obtain the optimally false data that should be injected into the forecasting model input so as to expand the prediction deviation as much as possible. Then, as the optimization model is non‐differentiable, a particle swarm optimization‐based method is developed to solve the optimization problem, in which the near‐optimal solution is able to be explored, directing the false data that should be injected. At last, numerical studies of the proposed attack tactic are conducted on different‐hour ahead wind speed forecasting models, revealing the feasibility and effectiveness.

Abstract Extensive inverter‐based power sources (IPS) impose significant challenges on the restoration of high renewable penetrated power systems (HRPPS). To enhance HRPPS resilience, the proper utilization of IPSs must be implemented. Combining frequency dynamics of IPSs and synchronous generators, this paper proposes a coordinated restoration method for multi‐type power sources after a major blackout. First, interactions between synchronous generators and IPSs are systematically analyzed. Based on this, output characteristics and constraints of IPSs in the power sources restoration process are quantified. Second, the dynamic frequency regulation capability (DFRC) of restored systems is quantified based on a unified transfer function structure model. Then the maximum power disturbance that restored systems can bear is derived based on DFRC indices including the maximum frequency deviation and the rate of change of frequency. Third, considering interactions between power sources and the DFRC of restored systems, a coordinated restoration optimization model of multi‐type power sources is proposed. Finally, case studies based on a modified IEEE 39‐bus system are simulated to verify the applicability and superiority of the proposed method. Meanwhile, results show that the proposed method for quantifying DFRC is more suitable for HRPPSs than traditional inertia‐based methods.

Abstract Background Cerebral malaria (CM) is the most lethal complication of malaria, and survivors usually endure neurological sequelae. Notably, the cytotoxic effect of infiltrating Plasmodium-activated CD8+ T cells on cerebral microvasculature endothelial cells is a prominent feature of the experimental CM (ECM) model with blood–brain barrier disruption. However, the damage effect of CD8+ T cells infiltrating the brain parenchyma on neurons remains unclear. Based on the immunosuppressive effect of the PD-1/PD-L1 pathway on T cells, our previous study demonstrated that the systemic upregulation of PD-L1 to inhibit CD8+ T cell function could effectively alleviate the symptoms of ECM mice. However, it has not been reported whether neurons can suppress the pathogenic effect of CD8+ T cells through the PD-1/PD-L1 negative immunomodulatory pathway. As the important inflammatory factor of CM, interferons can induce the expression of PD-L1 via different molecular mechanisms according to the neuro-immune microenvironment. Therefore, this study aimed to investigate the direct interaction between CD8+ T cells and neurons, as well as the mechanism of neurons to alleviate the pathogenic effect of CD8+ T cells through up-regulating PD-L1 induced by IFNs. Methods Using the ECM model of C57BL/6J mice infected with Plasmodium berghei ANKA (PbA), morphological observations were conducted in vivo by electron microscope and IF staining. The interaction between the ECM CD8+ T cells (immune magnetic bead sorting from spleen of ECM mice) and primary cultured cortical neurons in vitro was observed by IF staining and time-lapse photography. RNA-seq was performed to analyze the signaling pathway of PD-L1 upregulation in neurons induced by IFNβ or IFNγ, and verified through q-PCR, WB, IF staining, and flow cytometry both in vitro and in vivo using IFNAR or IFNGR gene knockout mice. The protective effect of adenovirus-mediated PD-L1 IgGFc fusion protein expression was verified in ECM mice with brain stereotaxic injection in vivo and in primary cultured neurons via viral infection in vitro. Results In vivo, ECM mice showed infiltration of activated CD8+ T cells and neuronal injury in the brain parenchyma. In vitro, ECM CD8+ T cells were in direct contact with neurons and induced axonal damage, as an active behavior. The PD-L1 protein level was elevated in neurons of ECM mice and in primary cultured neurons induced by IFNβ, IFNγ, or ECM CD8+ T cells in vitro. Furthermore, the IFNβ or IFNγ induced neuronal expression of PD-L1 was mediated by increasing STAT1/IRF1 pathway via IFN receptors. The increase of PD-L1 expression in neurons during PbA infection was weakened after deleting the IFNAR or IFNGR. Increased PD-L1 expression by adenovirus partially protected neurons from CD8+ T cell-mediated damage both in vitro and in vivo. Conclusion Our study demonstrates that both type I and type II IFNs can induce neurons to upregulate PD-L1 via the STAT1/IRF1 pathway mediated by IFN receptors to protect against activated CD8+ T cell-mediated damage, providing a targeted pathway to alleviate neuroinflammation during ECM. Graphical Abstract

PurposeAnalyze the clinical manifestations, laboratory tests, and imaging data of testicular torsion to provide clinical insights for timely and accurate diagnosis and treatment of testicular torsion.MethodsA retrospective analysis was conducted on the clinical data of 67 pediatric patients suspected of testicular torsion, admitted and subjected to surgical exploration from June 2018 to June 2023. Based on whether the torsed testicle was excised during surgery, the patients were divided into orchiectomy group (40 cases) and orchidopexy group (27 cases). Combining clinical symptoms, signs, ultrasound examinations, and laboratory tests, the study aimed to summarize the influencing factors on the onset, diagnosis, and treatment of testicular torsion.ResultsThe clinical manifestations of all 67 pediatric patients were generally typical. Color Doppler Flow Imaging (CDFI) and surgical exploration were performed for all cases, and the results were consistent. Testicular color doppler ultrasound suggested reduced or absent blood flow, leading to surgical treatment in all cases. All patients had unilateral testicular torsion, with 46 cases (68.66%) on the left side and 21 cases (31.34%) on the right side. Intrafunicular torsion occurred in 60 cases (89.55%), while extrafunicular torsion occurred in 7 cases (10.45%). The onset distribution was as follows: 20 cases in spring, 16 cases in summer, 16 cases in autumn, and 15 cases in winter. Univariate analysis indicated significant statistical differences in age, degree of testicular torsion, duration of symptoms, NEUT, NLR, and occurrence of tunica fluid between the two groups of patients. Multivariate logistic regression analysis showed that the duration of symptoms and the occurrence of hydrocele were independent risk factors for determining testicular viability.ConclusionTesticular torsion is more common in children and adolescents, with clinical manifestations including scrotal pain, scrotal redness and swelling, abdominal pain, nausea, and vomiting. In the early stages of testicular torsion, inflammatory markers in the blood increase, and preoperative ultrasound indicates hydrocele. This suggests that the testicle is in an early twisted state, with good viability and potential for preservation.

Goji berries are a small-fruited shrub with industrial importance whose fruit considered beneficial in both fresh and dried forms. Current germplasms of goji berries include small fruits with a short shelf life, less sweet and bitter taste, and a lack of appropriate genetic information. This study aimed to employ whole genome resequencing to generate an ultra-dense bin linkage map and to elucidate the genetic basis of goji fruit quality and size using quantitative trait loci (QTL) mapping analysis in a cross-pollinated hybrid population. To achieve this goal, human sensory tests were carried out to determine the bitter taste (BT) and sweet taste (ST), and to quantify the soluble solid content (SSC), fruit firmness (FF), and fruit size-related traits of fresh goji fruits over three or four years. The results revealed that the goji bin linkage map based on resequencing spanned a total length of 966.42 cM and an average bin interval of 0.03 cM. Subsequent variant calling and ordering resulted in 3,058 bins containing 35,331 polymorphic markers across 12 chromosomes. A total of 99 QTLs, with individual loci in different environments explaining a phenotypic variance of 1.21-16.95% were identified for the studied traits. Ten major effects, including colocalized QTLs corresponding to different traits, were identified on chromosomes 1, 3, 5, 6, 7, and 8, with a maximum Logarithm of Odds (LOD) of 29.25 and 16.95% of explained phenotypic variance (PVE). In addition, four stable loci, one for FF, one for fruit weight (FW), and two for fruit shape index (FSI), were mainly mapped on chromosomes 5, 6, and 7, elucidating 2.10-16.95% PVE. These findings offer valuable insights into the genetic architecture of goji fruit traits along with identified specific loci and markers to further improve and develop sweeter, less bitter and larger fruited goji berry cultivars with extended shelf life.

Macrophage-based cell therapeutics is an emerging modality to treat cancer and repair tissue damage. A reproducible manufacturing and engineering process is central to fulfilling their therapeutic potential. Here, we establish a robust macrophage-manufacturing platform (Mo-Mac) and demonstrate that macrophage functionality can be enhanced by N1-methylpseudouridine (m1Ψ)-modified mRNA. Using single-cell transcriptomic analysis as an unbiased approach, we found that >90% cells in the final product were macrophages while the rest primarily comprised T cells, B cells, natural killer cells, promyelocytes, promonocytes, and hematopoietic stem cells. This analysis also guided the development of flow-cytometry strategies to assess cell compositions in the manufactured product to meet requirements by the National Medical Products Administration. To modulate macrophage functionality, as an illustrative example we examined whether the engulfment capability of macrophages could be enhanced by mRNA technology. We found that efferocytosis was increased in vitro when macrophages were electroporated with m1Ψ-modified mRNA encoding CD300LF (CD300LF-mRNA-macrophage). Consistently, in a mouse model of acute liver failure, CD300LF-mRNA-macrophages facilitated organ recovery from acetaminophen-induced hepatotoxicity. These results demonstrate a GMP-compliant macrophage-manufacturing process and indicate that macrophages can be engineered by versatile mRNA technology to achieve therapeutic goals.

Zizania latifolia has been observed to generate floating mats due to water level fluctuations and wind-waves, leading to significant detrimental impacts on both water quality and biodiversity. The key to controlling and monitoring the spread and movement of Zizania floating is the early detection of outbreaks and the clarification of its formation mechanisms in response to water levels and wind actions. The temporal and spatial resolutions of conventional remote sensing monitoring methods are challenging to satisfy the requirements for continuous and accurate tracking of Zizania floating, which undergoes daily movement. This study develops a timely and accurate monitoring method for Zizania floating by calculating the Normalized Difference Vegetation Index (NDVI) from high spatiotemporal resolution PlanetScope (PS) imagery and building a decision tree on the Google Earth Engine (GEE) platform. Taking the Zizania floating outbreak in Honghu Wetland as the subject of our study, we extracted the continuous movement trajectories of Zizania floating from May to September 2019. Subsequently, we analyzed the interrelationship between the formation of Zizania floating and hydrometeorological factors. We then investigated the effects of Zizania floating on water quality and biodiversity. The results show that: (1) The integration of PS imagery and the GEE platform holds the potential to simplify the workload of remote sensing data processing. Based on the difference in NDVI between water bodies and Zizania floating, the dynamic expansion and reduction areas of the Zizania floating were successfully extracted by setting the threshold at 0.3, enabling timely and accurate tracking. (2) Abrupt fluctuations in water levels during brief time intervals serve as the primary trigger for Zizania floating. Additionally, wind speed during the same timeframe acts as a catalyst for the emergence of Zizania floating, with wind direction influencing its movement. (3) The outbreak of Zizania floating significantly elevates the concentrations of total nitrogen (TN), total phosphorus (TP), chemical oxygen demand (CODmn), and total ammonia nitrogen (TAN), while concurrently reducing the dissolved oxygen (DO) concentration in water bodies. The prolonged presence and movement of Zizania floating has reduced the biodiversity of the wetland ecosystem. Zizania floating mats present unique challenges due to their unpredictability, complicating the monitoring and tracking processes. It is necessary to develop a prompt, accurate, and cost-effective detection program for Zizania floating to reduce the risk it poses to wetland ecosystems.

ObjectiveTo investigate whether using Zishen Yutai Pills (ZYP) following embryo transfer would affect the live birth rate in frozen-thawed embryo transfer (FET) cycles.MethodsA retrospective analysis was performed on 15044 FET cycles in the Reproductive Medicine Center of The Affiliated Chenggong Hospital of Xiamen University from January 2013 to December 2020. Patients who used Zishen Yutai Pills were defined as Zishen Yutai Pills Group (ZYP, n=2735), while patients who did not use them were defined as Non- Zishen Yutai Pills Group (Non-ZYP, n=12309). The propensity score matching method was used to control for potential confounders between the two groups, and logistic regression analysis was also used to assess whether using ZYP would affect the live birth rate.ResultsAfter propensity score matching, basic characteristics were similar between the two groups. Using ZYP did not increase the pregnancy rate (51.5% vs. 52.7%, P=0.372), and live birth rate (43.0% vs. 44.7%, P=0.354). This was also confirmed by the logistic regression analysis results (OR=0.95, 95%CI=0.85-1.06). In the subgroup analysis of the endometrial preparation protocols, however, it was found that the use of ZYP in patients with natural cycles increased the live birth rate (47.4% vs. 41.5%, P=0.004). A significant interaction between endometrial preparation and ZYP was found (OR=1.38, 95%CI=1.07-1.79) in the multivariate model.ConclusionThe use of ZYP may not improve the live birth rate of unselected patients in FET cycles. However, a future study is needed on the effect of ZYP in natural cycles for endometrial preparation.

The hypometabolism induced by fasting has great potential in maintaining health and improving survival in extreme environments, among which thyroid hormone (TH) plays an important role in the adaptation and the formation of new energy metabolism homeostasis during long-term fasting. In the present review, we emphasize the potential of long-term fasting to improve physical health and emergency rescue in extreme environments, introduce the concept and pattern of fasting and its impact on the body’s energy metabolism consumption. Prolonged fasting has more application potential in emergency rescue in special environments. The changes of THs caused by fasting, including serum biochemical characteristics, responsiveness of the peripheral and central hypothalamus-pituitary-thyroid (HPT) axis, and differential changes of TH metabolism, are emphasized in particular. It was proposed that the variability between brain and liver tissues in THs uptake, deiodination activation and inactivation is the key regulatory mechanism for the cause of peripheral THs decline and central homeostasis. While hypothalamic tanycytes play a pivotal role in the fine regulation of the HPT negative feedback regulation during long-term fasting. The study progress of tanycytes on thyrotropin-releasing hormone (TRH) release and deiodination is described in detail. In conclusion, the combination of the decrease of TH metabolism in peripheral tissues and stability in the central HPT axis maintains the basal physiological requirement and new energy metabolism homeostasis to adapt to long-term food scarcity. The molecular mechanisms of this localized and differential regulation will be a key research direction for developing measures for hypometabolic applications in extreme environment.

Imaginary-time response functions of finite-temperature quantum systems are often obtained with methods that exhibit stochastic or systematic errors. Reducing these errors comes at a large computational cost—in quantum Monte Carlo simulations, the reduction of noise by a factor of two incurs a simulation cost of a factor of four. In this paper, we relate certain imaginary-time response functions to an inner product on the space of linear operators on Fock space. We then show that data with noise typically does not respect the positive definiteness of its associated Gramian. The Gramian has the structure of a Hankel matrix. As a method for denoising noisy data, we introduce an alternating projection algorithm that finds the closest positive definite Hankel matrix consistent with noisy data. We test our methodology at the example of fermion Green's functions for continuous-time quantum Monte Carlo data and show remarkable improvements of the error, reducing noise by a factor of up to 20 in practical examples. We argue that Hankel projections should be used whenever finite-temperature imaginary-time data of response functions with errors is analyzed, be it in the context of quantum Monte Carlo, quantum computing, or in approximate semianalytic methodologies.

Abstract Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cancer cell‐based vaccination is limited by interference from immunosuppressive senescence‐associated secretory phenotype and pro‐tumorigenic capacity of senescent cells. Here, a senescent cancer cell‐based nanovaccine with strong immunogenicity and favorable potential for immunotherapy is reported. The biomimetic nanovaccine integrating a senescent cancer cell membrane‐coated nanoadjuvant outperforms living senescent cancer cells in enhancing dendritic cells (DCs) internalization, improving lymph node targeting, and enhancing immune responses. In contrast to nanovaccines generated from immunogenic cell death‐induced tumor cells, senescent nanovaccines facilitate DC maturation, eliciting superior antitumor protection and improving therapeutic outcomes in melanoma‐challenged mice with fewer side effects when combined with αPD‐1. The study suggests a versatile biomanufacturing approach to maximize immunogenic potential and minimize adverse effects of senescent cancer cell‐based vaccination and advances the design of biomimetic nanovaccines for cancer immunotherapy.

Background: Associations between napping and incident atrial fibrillation (AF) remain unknown, and few studies have accounted for dynamic transitions between AF and dementia. Objectives: The purpose of this study was to evaluate associations between napping with incident AF and the dynamic transitions of AF and dementia, as well as the mediation pathway of left ventricular (LV) size and function. Methods: A total of 476,588 participants from UK Biobank were included. Napping frequency and other sleep behaviors were evaluated. Incident AF, dementia, and mortality were ascertained via linkage to external registry databases. LV size and function indices were obtained from cardiovascular magnetic resonance imaging phenotypes. A multistate survival analysis was conducted to examine daytime napping in relation to dynamic transitions. Weighed AF genetic risk score was calculated. Results: Frequent daytime napping, compared to never/rarely napping, was associated with a 1.17-fold AF risk (HR: 1.17; 95% CI: 1.12-1.22), which persisted after controlling for other sleep behaviors. Genetic predisposition significantly modified associations between napping and AF (P for interaction

During the COVID-19 pandemic, many online lessons for emergency remote teaching (ERT) were recorded. However, little is known about how these recordings can be reused as resources for students’ active learning. This study aimed to design a post-video learning approach that uses recorded videos of lessons to remediate students’ learning losses associated with the pedagogical challenges of ERT. Two classes (54 students in total) with two teachers of general studies and mathematics in a Hong Kong primary school participated in a quasi-experimental study in which they used an approach integrating video selection, visualizations of classroom dialogues, a discussion forum, and quizzes for 10 weeks. After the intervention, the students’ mathematics knowledge had improved significantly relative to a comparison group, while the general studies class did not show significant changes. Eight students and two teachers were interviewed about their experiences with the post-video learning approach. The approach appeared to be a pedagogically meaningful way of engaging students in active learning activities and addressing the challenges raised by ERT by recycling recorded lessons. The results of this study also suggest that recorded lessons can be useful learning materials beyond tertiary education as they cater to younger learners’ needs in video-based learning by, for example, segmenting class videos, using visualization for easier viewing, and including discussion forums and quizzes for enhanced interaction. The design implications of using video segments and visualized representations of classroom interactions as learning materials and how to foster knowledge co-construction through forums and quizzes are also discussed.

Abstract Various studies have focused on the application of fibrin sealants (FS) in thyroid surgery. Utilizing a meta-analysis, this systematic review analyzed the findings of recent randomized controlled trials on the safety and efficacy of FS in patients who underwent thyroidectomy. The Cochrane Library, Web of Science, Embase, PubMed, and Medline databases were searched for relevant studies, without any language restrictions. Seven randomized controlled trials were included in the originally identified 69 studies. Overall, 652 patients received FS during thyroid surgery; their outcomes were compared with those of conventionally treated patients. The primary outcomes were total volume of wound drainage, length of hospitalization, and operative time. Significant differences were observed in the total volume of wound drainage (mean deviation (MD): -29.75, 95% confidence interval (CI): -55.39 to -4.11, P = 0.02), length of hospitalization (MD: -0.84, 95% CI: -1.02 to -0.66, P

Abstract Human activities have increased with urbanisation in the Erhai Lake Basin, considerably impacting its eco-environmental quality (EEQ). This study aims to reveal the evolution and driving forces of the EEQ using water benefit–based ecological index (WBEI) in response to human activities and policy variations in the Erhai Lake Basin from 1990 to 2020. Results show that (1) the EEQ exhibited a pattern of initial degradation, subsequent improvement, further degradation and a rebound from 1990 to 2020, and the areas with poor and fair EEQ levels mainly concentrated around the Erhai Lake Basin with a high level of urbanisation and relatively flat terrain; (2) the EEQ levels were not optimistic in 1990, 1995 and 2015, and areas with poor and fair EEQ levels accounted for 43.41%, 47.01% and 40.05% of the total area, respectively; and (3) an overall improvement in the EEQ was observed in 1995–2000, 2000–2005, 2005–2009 and 2015–2020, and the improvement was most significant in 1995–2000, covering an area of 823.95 km2 and accounting for 31.79% of the total area. Results also confirmed that the EEQ changes in the Erhai Lake Basin were primarily influenced by human activities and policy variations. Moreover, these results can provide a scientific basis for the formulation and planning of sustainable development policy in the Erhai Lake Basin.

Abstract Additive manufacturing provides an efficient way of producing metallic components with complex geometries. Their microstructure is substantially different to those from conventional processing, creating opportunities for manipulating the final microstructure and properties via heat treatment. Here, we demonstrate that as-built heterostructures in an Al-Zn-Mg-Cu-Nb alloy produced during the solidification of molten pools provide a driving force and additional Zener pinning sources for recrystallization. This creates a bimodal grain structure after solution treatment, causing additional hetero-deformation-induced strengthening and hardening. Coarse grains are found to promote work hardening and blunt the propagate of cracks during deformation, increasing ductility. Together with precipitation strengthening from a high number density nanoprecipitates, the simultaneous improvement of strength and ductility in a highly alloyed Al-Zn-Mg-Cu-Nb alloy is achieved. These results provide a simple strategy for the development of additively manufactured age-hardening alloys with improved strength and ductility for high performance structural applications.

Abstract Background In lung transplantation (LTx) surgery, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide mechanical circulatory support to patients with cardiopulmonary failure. However, the use of heparin in the administration of ECMO can increase blood loss during LTx. This study aimed to evaluate the safety of heparin-free V-A ECMO strategies. Methods From September 2019 to April 2022, patients who underwent lung transplantation at the First Affiliated Hospital of Guangzhou Medical University were retrospectively reviewed. A total of 229 patients were included, including 117 patients in the ECMO group and 112 in the non-ECMO group. Result There was no significant difference in the incidence of thrombus events and bleeding requiring reoperation between the two groups. The in-hospital survival rate after single lung transplantation (SLTx) was 81.08%in the ECMO group and 85.14% in the Non-ECMO group, (P = 0.585). The in-hospital survival rate after double lung transplantation (DLTx) was 80.00% in the ECMO group and 92.11% in the Non-ECMO groups (P = 0.095). Conclusions In conclusion, the findings of this study suggest that the heparin-free V-A ECMO strategy in lung transplantation is a safe approach that does not increase the incidence of perioperative thrombotic events or bleeding requiring reoperation.

Objective The purpose of this study was to explore the effect of sodium salicylate (SS) on semen preservation and metabolic regulation in goats. Methods Under the condition of low temperature, SS was added to goat semen diluent to detect goat sperm motility, plasma membrane, acrosome, antioxidant capacity, mitochondrial membrane potential (MMP) and metabonomics. Results The results show that at the 8th day of low-temperature storage, the sperm motility of the 20 μM SS group was 66.64%, and the integrity rates of the plasma membrane and acrosome were both above 60%, significantly higher than those of the other groups. The activities of catalase and superoxide dismutase in the sperm of the 20 μM SS group were significantly higher than those of the control group, the contents of reactive oxygen species and malondialdehyde were significantly lower than those in the control group, the MMP was significantly higher than that in the control group, and the contents of Ca2+ and total cholesterol were significantly higher than those in the control group. Through metabonomics analysis, there were significant metabolic differences between the control group and the 20 μM SS group. Twenty of the most significant metabolic markers were screened, mainly involving five metabolic pathways, of which nicotinic acid and nicotinamide metabolic pathways were the most significant. Conclusion The results indicate that SS can effectively improve the low-temperature preservation quality of goat sperm.