Effects of dietary melatonin supplementation on growth performance and intestinal health of rice field eel (Monopterus albus).

The objective was to assess the impact of melatonin supplementation on the growth performance and intestinal health of rice field eel, Monopterus albus. Three hundred and sixty fish (28.46 ± 0.24 g) were fed five diets supplemented with melatonin of 0, 30, 60, 120, and 240 mg/kg for 70 days. The study found that the variables FBW, WGR, SGR, and FCR exhibited a statistically significant quadratic relationship (P < 0.05) with the dietary melatonin concentrations, and the highest FBW, WGR and SGR as well as lowest FCR were observed in the 120 mg/kg melatonin group, digestive enzymes activities (such as amylase, trypsin, and lipase) also had significant quadratic relationship (P < 0.05), and the highest intestinal villus height and goblet cells were found in the 120 mg/kg diet (P < 0.01), melatonin in diets significantly increased SOD and CAT activities in serum, up-regulated the expression of anti-inflammatory factors (IL-10) and tight junction protein (ZO-1), and down-regulated the expression of pro-inflammatory factors (IL-1ß, IL-8, IL-15, and TNF-α) in the gut, dietary melatonin improved the intestinal microflora compositions, in the group that supplementation a dosage of 120 mg/kg, there was a noticeable rise in the abundance of Firmicutes and the ratio of Firmicutes/Bacteroidota, compared with control group (P < 0.1). Conclusively, dietary supplementation of melatonin promoted growth performance, enhanced intestinal immune capacity and serum antioxidant level, and improved intestinal morphology properties and intestinal flora composition in M. albus. In conclusion, based on quadratic broken-line regression analysis of WGR and FCR, the optimal concentration of melatonin to be supplied is predicted to be 146-148 mg/kg.

Trends in cardiovascular health among US adults by glycemic status based on Life's Essential 8.

OBJECTIVE: We aimed to assess the secular trends in cardiovascular health (CVH) among U.S. adults with different glycemic statuses based on the Life's Essential 8 (LE8). METHODS: This cross-sectional study used nationally representative data from 6 cycles of the National Health and Nutrition Examination Surveys between 2007 and 2018. Survey-weighted linear models were used to assess time trends in LE8 scores. Stratified analyses and sensitivity analyses were conducted to validate the stability of the results. RESULTS: A total of 23,616 participants were included in this study. From 2007 to 2018, there was no significant improvement in overall CVH and the proportion of ideal CVH among participants with diabetes and prediabetes. We observed an opposite trend between health behavior and health factors in the diabetes group, mainly in increasing physical activity scores and sleep scores (P for trend<0.001), and declining BMI scores [difference, -6.81 (95% CI, -12.82 to -0.80)] and blood glucose scores [difference, -6.41 (95% CI, -9.86 to -2.96)]. Dietary health remained at a consistently low level among participants with different glycemic status. The blood lipid scores in the prediabetes group improved but were still at a lower level than other groups. Education/income differences persist in the CVH of participants with diabetes or prediabetes, especially in health behavior factors. Sensitivity analyses of the absolute difference and change in proportion showed a consistent trend. CONCLUSIONS: Trends in CVH among participants with diabetes or prediabetes were suboptimal from 2007 to 2018, with persistent education/income disparities.

Biochemical, Histological, and Transcriptomic Analyses Reveal Underlying Differences in Flesh Quality between Wild and Farmed Ricefield Eel (Monopterus albus).

The present study aimed to systematically investigate the underlying differences in flesh quality between wild and farmed Monopterus albus. Fifteen healthy M. albus per group with an average body weight of 45 g were sampled to analyze muscle parameters by biochemical indicators, histomorphology, and molecular biology. Compared with the wild fish, the farmed M. albus in flesh had lower crude protein, collagen, lysine, histidine, total amino acids, SFA, n-3 PUFA contents, and n-3/n-6 ratio (p < 0.05), and higher moisture, crude lipid, crude ash, MUFA, n-6PUFA, and total PUFA contents (p < 0.05). The thawing loss, drip loss, steaming loss, and boiling loss in the farmed group were significantly higher, and hardness, springiness, cohesiveness, gumminess, chewiness, and resilience were significantly lower than those in the wild group (p < 0.05). In addition, higher muscle fiber density and lower muscle fiber diameter were observed in wild M. albus (p < 0.05). In muscle transcriptome profiling, differentially expressed genes and enriched pathways are primarily associated with muscle development, protein synthesis, catabolism, lipid metabolism, and immunity. To the best of our knowledge, this is the first investigation that compares the flesh quality between wild and farmed M. albus in terms of biochemistry, histology, and molecular biology levels. Overall, wild M. albus had a higher nutritional value and texture quality than farmed M. albus.

Multi-Target Feeding-Behavior Recognition Method for Cows Based on Improved RefineMask.

Within the current process of large-scale dairy-cattle breeding, to address the problems of low recognition-accuracy and significant recognition-error associated with existing visual methods, we propose a method for recognizing the feeding behavior of dairy cows, one based on an improved RefineMask instance-segmentation model, and using high-quality detection and segmentation results to realize the recognition of the feeding behavior of dairy cows. Firstly, the input features are better extracted by incorporating the convolutional block attention module into the residual module of the feature extraction network. Secondly, an efficient channel attention module is incorporated into the neck design to achieve efficient integration of feature extraction while avoiding the surge of parameter volume computation. Subsequently, the GIoU loss function is used to increase the area of the prediction frame to optimize the convergence speed of the loss function, thus improving the regression accuracy. Finally, the logic of using mask information to recognize foraging behavior was designed, and the accurate recognition of foraging behavior was achieved according to the segmentation results of the model. We constructed, trained, and tested a cow dataset consisting of 1000 images from 50 different individual cows at peak feeding times. The method's effectiveness, robustness, and accuracy were verified by comparing it with example segmentation algorithms such as MSRCNN, Point_Rend, Cascade_Mask, and ConvNet_V2. The experimental results show that the accuracy of the improved RefineMask algorithm in recognizing the bounding box and accurately determining the segmentation mask is 98.3%, which is higher than that of the benchmark model by 0.7 percentage points; for this, the model parameter count size was 49.96 M, which meets the practical needs of local deployment. In addition, the technologies under study performed well in a variety of scenarios and adapted to various light environments; this research can provide technical support for the analysis of the relationship between cow feeding behavior and feed intake during peak feeding periods.

Regulatory roles of the second messenger c-di-GMP in beneficial plant-bacteria interactions.

The rhizosphere system of plants hosts a diverse consortium of bacteria that confer beneficial effects on plant, such as plant growth-promoting rhizobacteria (PGPR), biocontrol agents with disease-suppression activities, and symbiotic nitrogen fixing bacteria with the formation of root nodule. Efficient colonization in planta is of fundamental importance for promoting of these beneficial activities. However, the process of root colonization is complex, consisting of multiple stages, including chemotaxis, adhesion, aggregation, and biofilm formation. The secondary messenger, c-di-GMP (cyclic bis-(3'-5') dimeric guanosine monophosphate), plays a key regulatory role in a variety of physiological processes. This paper reviews recent progress on the actions of c-di-GMP in plant beneficial bacteria, with a specific focus on its role in chemotaxis, biofilm formation, and nodulation.

Comparing the effects of magnetite-mediated direct interspecies electron transfer with biogas mixing-driven interspecies hydrogen transfer on anaerobic digestion.

Although the promotive effect of direct interspecies electron transfer (DIET) on methane production has been well-documented, the practical applicability of DIET in different scenarios have not yet been systematically studied. This study compared the effects of magnetite-mediated DIET with conventional biogas mixing-driven interspecies hydrogen transfer (IHT) on anaerobic digestion (AD) of swine manure (SM). Compared with control, magnetite supplementation, biogas circulation, and their integration enhanced the CH4 yield by 19.3%, 25.9%, and 26.2%, respectively. Magnetite mainly enriched DIET-related syntrophic bacteria (Anaerolineae and Synergistia) and methanogens (Methanosarcina) to accelerate acidification and establish DIET, while biogas circulation mainly enriched hydrolytic bacteria (Clostridia) and hydrogenotrophic methanogens (Methanolinea and Methanobacterium) to promote hydrolysis and accelerate IHT. Coupling magnetite addition with biogas circulation led to the enrichment of the above six microorganisms to different extents. The effectiveness of the strategies for lowering the H2 pressure followed: magnetite + biogas circulation ≈ biogas circulation > magnetite. Under stress-free environment, the enhancement effect of magnetite-induced DIET was not even as pronounced as biogas circulation-a simple and common mixing strategy in commercial AD plants, and the promotion effect of magnetite was insignificant in the well-mixed digesters. In short, the magnetite-mediated DIET is not always effective in improving AD of SM.

Identifying drivers of non-stationary climate-growth relationships of European beech.

The future performance of the widely abundant European beech (Fagus sylvatica L.) across its ecological amplitude is uncertain. Although beech is considered drought-sensitive and thus negatively affected by drought events, scientific evidence indicating increasing drought vulnerability under climate change on a cross-regional scale remains elusive. While evaluating changes in climate sensitivity of secondary growth offers a promising avenue, studies from productive, closed-canopy forests suffer from knowledge gaps, especially regarding the natural variability of climate sensitivity and how it relates to radial growth as an indicator of tree vitality. Since beech is sensitive to drought, we in this study use a drought index as a climate variable to account for the combined effects of temperature and water availability and explore how the drought sensitivity of secondary growth varies temporally in dependence on growth variability, growth trends, and climatic water availability across the species' ecological amplitude. Our results show that drought sensitivity is highly variable and non-stationary, though consistently higher at dry sites compared to moist sites. Increasing drought sensitivity can largely be explained by increasing climatic aridity, especially as it is exacerbated by climate change and trees' rank progression within forest communities, as (co-)dominant trees are more sensitive to extra-canopy climatic conditions than trees embedded in understories. However, during the driest periods of the 20th century, growth showed clear signs of being decoupled from climate. This may indicate fundamental changes in system behavior and be early-warning signals of decreasing drought tolerance. The multiple significant interaction terms in our model elucidate the complexity of European beech's drought sensitivity, which needs to be taken into consideration when assessing this species' response to climate change.

Unveiling the A-to-I mRNA editing machinery and its regulation and evolution in fungi.

A-to-I mRNA editing in animals is mediated by ADARs, but the mechanism underlying sexual stage-specific A-to-I mRNA editing in fungi remains unknown. Here, we show that the eukaryotic tRNA-specific heterodimeric deaminase FgTad2-FgTad3 is responsible for A-to-I mRNA editing in Fusarium graminearum. This editing capacity relies on the interaction between FgTad3 and a sexual stage-specific protein called Ame1. Although Ame1 orthologs are widely distributed in fungi, the interaction originates in Sordariomycetes. We have identified key residues responsible for the FgTad3-Ame1 interaction. The expression and activity of FgTad2-FgTad3 are regulated through alternative promoters, alternative translation initiation, and post-translational modifications. Our study demonstrates that the FgTad2-FgTad3-Ame1 complex can efficiently edit mRNA in yeasts, bacteria, and human cells, with important implications for the development of base editors in therapy and agriculture. Overall, this study uncovers mechanisms, regulation, and evolution of RNA editing in fungi, highlighting the role of protein-protein interactions in modulating deaminase function.

Mechanism and deterioration pattern of sandstone surrounding rock voiding at bottom of heavy-haul railway tunnel.

This study combines laboratory experiments and discrete element simulation methods to analyze the mechanism and deterioration patterns of sandstone surrounding rock voiding the bottom of a heavy-haul railway tunnel. It is based on previously acquired measurement data from optical fiber grating sensors installed in the Taihangshan Mountain Tunnel of the Wari Railway. By incorporating rock particle wastage rate results, a method for calculating the peak strength and elastic modulus attenuation of surrounding rock is proposed. Research indicates that the operation of heavy-haul trains leads to an instantaneous increase in the dynamic water pressure on the bottom rock ranging 144.4-390.0%, resulting in high-speed water flow eroding the rock. After 1-2 years of operation, the bottom water and soil pressures increase by 526.5% and 390.0%, respectively. Focusing on sandstone surrounding rock with high observability, laboratory experiments were conducted to monitor the degradation stages of infiltration, particle loss, and voiding of rock under the action of dynamic water flow. The impact of water flow on the "cone-shaped" bottom rock deformation was also clarified. The extent of rock deterioration and voiding was determined using miniature water and soil pressure sensors in conjunction with discrete element numerical simulations. The measured rock particle loss was used as a criterion. Finally, a fitting approach is derived to calculate the peak strength and elastic modulus attenuation of surrounding rock, gaining insight into and providing a reference for the maintenance and disposal measures for the bottom operation of heavy-haul railway tunnels.

Effects on growth performance and immunity of Monopterus albus after high temperature stress.

To investigate the impact of the effect of high temperature stimulation on Monopterus albus larvae after a certain period of time, five experimental groups were established at different temperatures. Then, the M. albus under high temperature stress was fed at 30°C for 70 days. After that, the growth index of the M. albus was counted and analyzed. In terms of growth index, high temperature stress had significant effects on FCR, FBW, WGR, and SGR of M. albus (p < 0.05). The SR increased after being stimulated by temperature (p < 0.1). The study revealed that liver cells of M. albus were harmed by elevated temperatures of 36°C and 38°C. In the experimental group, the activities of digestive enzymes changed in the same trend, reaching the highest point in the 32°C group and then decreasing, and the AMS activity in the 38°C group was significantly different from that in the 30°C group (p < 0.05). The activities of antioxidase in liver reached the highest at 34°C, which was significantly different from those at 30°C (p < 0.05). In addition, the expression levels of TLR1, C3, TNF-α, and other genes increased in the experimental group, reaching the highest point at 34°C, and the expression level of the IL-1ß gene reached the highest point at 32°C, which was significantly different from that at 30°C (p < 0.05). However, the expression level of the IRAK3 gene decreased in the experimental group and reached its lowest point at 34°C (p < 0.05). The expression level of the HSP90α gene increased with the highest temperature stimulus and reached its highest point at 38°C (p < 0.05). In the α diversity index of intestinal microorganisms in the experimental group, the observed species, Shannon, and Chao1 indexes in the 34°C group were the highest (p < 0.05), and ß diversity analysis revealed that the intestinal microbial community in the experimental group was separated after high temperature stimulation. At the phylum level, the three dominant flora are Proteus, Firmicutes, and Bacteroides. Bacteroides and Macrococcus abundance increased at the genus level, but Vibrio and Aeromonas abundance decreased. To sum up, appropriate high-temperature stress can enhance the immunity and adaptability of M. albus. These results show that the high temperature stimulation of 32°C-34°C is beneficial to the industrial culture of M. albus.

1D hollow tubular/2D nanosheet hybrid dimensional porous carbon prepared by one-step carbonization using natural minerals as templates for supercapacitors.

The reasonable construction of one-dimensional (1D)/two-dimensional (2D) hybrid dimensional porous carbon materials with complementary advantages and disadvantages is an important approach to addressing the structural and performance deficiencies of single carbon materials, while also significantly improving the electrochemical performance of super-capacitors. In this study, 1D hollow tubular/2D nanosheet hybrid dimensional porous carbon was synthesized through one-step carbonization using 1D fibrous brucite and 2D layered magnesium carbonate hydroxide as templates. By adjusting the feed ratio of 1D fibrous and 2D layered templates, the morphology, pore structure and specific surface area (SSA) of the prepared 1D hollow tubular/2D nanosheet hybrid dimensional porous carbon were controlled. The prepared hybrid dimensional porous carbons were characterized using scanning electron microscope (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption-desorption. And their electrochemical performance was also studied by cyclic voltammograms (CV), galvanostatic charge/discharge (GCD) and electrochemical impedance spectroscopy (EIS). The results show that the use of templates with different dimensions significantly influences the morphology, pore structure, SSA and electrochemical performance of the synthesized hybrid dimensional porous carbon. The hybrid dimensional porous carbon (3F) exhibits a high specific capacitance and excellent cycling stability. 3F demonstrates the specific capacitance of 245.3 F g-1 at 1 A g-1. Furthermore, the capacity retention rate remains as high as 93.4% after 8000 cycles at 10 A g-1. This work reveals that hybrid dimensional porous carbon composed of 1D hollow carbon tubes and 2D carbon nanosheets has great potential for use in supercapacitor electrode materials.

The impact of maternal age on aneuploidy in oocytes: Reproductive consequences, molecular mechanisms, and future directions.

Age-related aneuploidy in human oocytes is a major factor contributing to decreased fertility and adverse reproductive outcomes. As females age, their oocytes are more prone to meiotic chromosome segregation errors, leading primarily to aneuploidy. Elevated aneuploidy rates have also been observed in oocytes from very young, prepubertal conceptions. A key barrier to developing effective treatments for age-related oocyte aneuploidy is our incomplete understanding of the molecular mechanisms involved. The challenge is becoming increasingly critical as more people choose to delay childbearing, a trend that has significant societal implications. In this review, we summarize current knowledge regarding the process of oocyte meiosis and folliculogenesis, highlighting the relationship between age and chromosomal aberrations in oocytes and embryos, and integrate proposed mechanisms of age-related meiotic disturbances across structural, protein, and genomic levels. Our goal is to spur new research directions and therapeutic avenues.

Constructing ultra-stable, high-energy, and flexible aqueous zinc-ion batteries using environment-friendly organic cathodes.

Due to their sustainability, environmental friendliness, high specific capacity, and rapid reaction kinetics, quinone cathodes have broad application prospects in aqueous zinc-ion batteries (AZIBs). However, conventional small-molecule quinone cathodes usually suffer from unavoidable dissolution, resulting in terrible cycling stability. Herein, based on a strategy of molecular structure optimization, calix[8]quinone (C8Q) is for the first time used as a cathode in AZIBs. By extending the structure of the classical small-molecule quinone cathode calix[4]quinone (C4Q), C8Q further adds four p-benzoquinone structural units, which significantly suppresses the dissolution of its discharge products and greatly improves the cycle stability of the cathode. Specifically, the C8Q cathode displays a discharge specific capacity of 207.2 mA h g-1 at 1 A g-1 and a long-life cycle stability (93 mA h g-1/10 A g-1/10000th). Even with a high active material loading of 11 mg cm-2, the Zn‖C8Q battery also exhibits high redox reversibility and remarkable electrochemical stability. Furthermore, the belt-shaped Zn‖C8Q battery has high stability and outstanding flexibility, indicating its promising application in flexible wearable electronic devices.

Feasibility and tolerability of eribulin-based chemotherapy versus other chemotherapy regimens for patients with metastatic triple-negative breast cancer: a single-centre retrospective study.

Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC. Method: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study's primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria. Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n = 45) and platinum-based therapy (n = 51). The follow-up period for all patients ended on 31 December 2022, and the median follow-up time was 18.3 months (range:0.7-27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median progression-free survival compared to platinum-based (hazard ratio (HR) = 0.41, p = 0.006), nab-paclitaxel-based (hazard ratio = 0.36, p = 0.001) and other chemotherapy (HR = 0.39, p < 0.001). Also, eribulin induced a remarkable prolongation of the median overall survival duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups. Conclusion: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted.

Analysis and validation of hub genes in neutrophil extracellular traps for the long-term prognosis of myocardial infarction.

INTRODUCTION: The study focuses on the long-term prognosis of myocardial infarction (MI) influenced by neutrophil extracellular traps (NETs). It also aims to analyze and validate relative hub genes in this process, in order to further explore new therapeutic targets that can improve the prognosis of MI. MATERIALS AND METHODS: We established a MI model in mice by ligating the left anterior descending branch (LAD) and conducted an 8-week continuous observation to study the dynamic changes in the structure and function of the heart in these mice. Meanwhile, we administered Apocynin, an inhibitor of NADPH Oxidase, which has also been shown to inhibit the formation of NETs, to mice undergoing MI surgery in order to compare. This study employed hematoxylin-eosin (HE) staining, echocardiography, immunofluorescence, and real-time quantitative PCR (RT-qPCR) to examine the impact of NETs on the long-term prognosis of MI. Next, datasets related to MI and NETs were downloaded from the GEO database, respectively. The Limma package of R software was used to identify differentially expressed genes (DEGs). After analyzing the "Robust Rank Aggregation (RRA)" package, we conducted a screening for robust differentially expressed genes (DEGs) and performed pathway enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to determine the functional roles of these robust DEGs. The protein-protein interaction (PPI) network was visualized and hub genes were filtered using Cytoscape. RESULTS: Immunofluorescence and qPCR results showed an increase in the expression of Myeloperoxidase (MPO) at week 1 and week 8 in the hearts of mice after MI. HE staining reveals a series of pathological manifestations in the heart of the MI group during 8 weeks, including enlarged size, disordered arrangement of cardiomyocytes, infiltration of inflammatory cells, and excessive deposition of collagen fibers, among others. The utilization of Apocynin could significantly improve these poor performances. The echocardiography displayed the cardiac function of the heart in mice. The MI group has a reduced range of heart movement and decreased ejection ability. Moreover, the ventricular systolic movement was found to be abnormal, and its wall thickening rate decreased over time, indicating a progressive worsening of myocardial ischemia. The Apocynin group, on the contrary, showed fewer abnormal changes in the aforementioned aspects. A total of 81 DEGs and 4 hub genes (FOS, EGR1, PTGS2, and HIST1H4H) were obtained. The results of RT-qPCR demonstrated abnormal expression of these four genes in the MI group, which could be reversed by treatment of Apocynin. CONCLUSION: The NETs formation could be highly related to MI and the long-term prognosis of MI can be significantly influenced by the NETs formation. Four hub genes, namely FOS, EGR1, PTGS2, and HIST1H4H, have the potential to be key genes related to this process. They could also serve as biomarkers for predicting MI prognosis and as targets for gene therapy.

LDH/MXene Synergistic Carrier Separation Effects to Improve the Photoelectric Catalytic Activities of Bi2WO6 Nanosheet Arrays.

Photoelectric catalysis is a green and efficient way to degrade pollutants, which has been paid more and more attention by researchers. Among them, Bi2WO3 has been proved to have excellent photocatalytic oxidation activity on its {001} facets. In this study, {001}-oriented facets with high exposure were successfully integrated into Bi2WO6 nanoplate arrays (Bi2WO6 NAs) to create a photoelectrode. This structure was grown in situ on an indium tin oxide (ITO) substrate. To promote photogenerated carrier separation efficiency and reduce agglomeration of Bi2WO6 photocatalysts, the electrochemical deposition of NiFe-layered double hydroxide (NiFe-LDH) and Ti3C2 (MXene) were introduced in this research to synergistically catalyze pollutant degradation. Morphology, spectral characterization, and electrochemical analysis jointly confirmed that the outstanding performance of hole capture behavior with LDH and electron conduction properties with MXene were the main reasons for the improvement in catalytic activity of the photoelectrode. Taking bisphenol A (BPA) as the model pollutant, the rate constant k of the NiFe-LDH/Ti3C2/Bi2WO6 NAs photoelectrode reaches 0.00196 min-1 under photoelectrocatalytic (PEC) conditions, which is 4.5 times that of the pure Bi2WO6 NAs photoelectrode. This work provides a new way to improve the reaction kinetics of the PEC degradation of pollutants.

Engineered Bacterial Biomimetic Vesicles Reprogram Tumor-Associated Macrophages and Remodel Tumor Microenvironment to Promote Innate and Adaptive Antitumor Immune Responses.

Tumor-associated macrophages (TAMs) are among the most abundant infiltrating leukocytes in the tumor microenvironment (TME). Reprogramming TAMs from protumor M2 to antitumor M1 phenotype is a promising strategy for remodeling the TME and promoting antitumor immunity; however, the development of an efficient strategy remains challenging. Here, a genetically modified bacterial biomimetic vesicle (BBV) with IFN-γ exposed on the surface in a nanoassembling membrane pore structure was constructed. The engineered IFN-γ BBV featured a nanoscale structure of protein and lipid vesicle, the existence of rich pattern-associated molecular patterns (PAMPs), and the costimulation of introduced IFN-γ molecules. In vitro, IFN-γ BBV reprogrammed M2 macrophages to M1, possibly through NF-κB and JAK-STAT signaling pathways, releasing nitric oxide (NO) and inflammatory cytokines IL-1ß, IL-6, and TNF-α and increasing the expression of IL-12 and iNOS. In tumor-bearing mice, IFN-γ BBV demonstrated a targeted enrichment in tumors and successfully reprogrammed TAMs into the M1 phenotype; notably, the response of antigen-specific cytotoxic T lymphocyte (CTL) in TME was promoted while the immunosuppressive myeloid-derived suppressor cell (MDSC) was suppressed. The tumor growth was found to be significantly inhibited in both a TC-1 tumor and a CT26 tumor. It was indicated that the antitumor effects of IFN-γ BBV were macrophage-dependent. Further, the modulation of TME by IFN-γ BBV produced synergistic effects against tumor growth and metastasis with an immune checkpoint inhibitor in an orthotopic 4T1 breast cancer model which was insensitive to anti-PD-1 mAb alone. In conclusion, IFN-γ-modified BBV demonstrated a strong capability of efficiently targeting tumor and tuning a cold tumor hot through reprogramming TAMs, providing a potent approach for tumor immunotherapy.

Synergistic π-Conjugation Organic Cathode for Ultra-Stable Aqueous Aluminum Batteries.

Rechargeable aqueous aluminum batteries (AABs) are promising energy storage technologies owing to their high safety and ultra-high energy-to-price ratio. However, either the strong electrostatic forces between high-charge-density Al3+ and host lattice, or sluggish large carrier-ion diffusion toward the conventional inorganic cathodes generates inferior cycling stability and low rate-capacity. To overcome these inherent confinements, a series of promising redox-active organic materials (ROMs) are investigated and a π-conjugated structure ROMs with synergistic C═O and C═N groups is optimized as the new cathode in AABs. Benefiting from the joint utilization of multi-redox centers and rich π-π intermolecular interactions, the optimized ROMs with unique ion coordination storage mechanism facilely accommodate complex active ions with mitigated coulombic repulsion and robust lattice structure, which is further validated via theoretical simulations. Thus, the cathode achieves enhanced rate performance (153.9 mAh g-1 at 2.0 A g-1 ) and one of the best long-term stabilities (125.7 mAh g-1 after 4,000 cycles at 1.0 A g-1 ) in AABs. Via molecular exploitation, this work paves the new direction toward high-performance cathode materials in aqueous multivalent-ion battery systems.

First molecular detection and genetic characterization of porcine circovirus 4 in the Gansu Province of China.

Since its initial discovery in the Hunan province of China, genomic DNA of porcine circovirus 4 (PCV4) has been detected in pigs across multiple provinces in China, as well as in South Korea. However, the prevalence of porcine circovirus type 4 in Gansu Province, China, remains unknown. To address this gap, we undertook an extensive study where we gathered 121 clinical samples displaying diverse clinical manifestations from pig farms in Gansu Province between 2022 and 2023. Employing a real-time fluorescence quantification method, we identified the presence of PCV4 genome. Out of the 121 clinical samples analyzed, 13 samples tested positive for PCV4, resulting in a positive rate of 10.74% (13/121). This finding confirms the presence of PCV4 in pig farms within Gansu Province, China. Furthermore, we successfully sequenced and analyzed the complete genomes of two distinct PCV4 strains, comparing them with 60 reference sequences archived in the GenBank database. The results revealed a high nucleotide homology (98.2-98.8%) between the strains obtained in this study and the PCV4 reference strains, indicating a relatively low evolutionary rate of the PCV4 genome. Phylogenetic analysis revealed that two strains in this study belong to PCV4a and PCV4c. As far as we know, this study marks the inaugural report on the molecular identification and genomic attributes of PCV4 in Gansu Province, China, offering valuable insights for devising preventive and control strategies against this emerging virus.