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Thymus is the important immune organ, responsible for T cell development and differentiation. The lower circulating T counts have been observed in patients who died from COVID-19 compared with survivors. Azvudine, also known as FNC, is a thymus-homing anti-SARS-CoV-2 drug in treating COVID-19 patients. In this study, single-cell transcriptome, proteomics, and parallel reaction monitoring (PRM) were applied to insight into the activation process of FNC in rat and SARS-CoV-2 rhesus monkey thymus. The results indicated that thymic immune cells possess a robust metabolic capacity for cytidine-analogue drugs such as FNC. Key enzymes involved in the FNC phosphorylation process, such as Dck, Cmpk1, and Nme2, were highly expressed in CD4+ T cells, CD8+ T cells, and DP (CD4+ CD8+) cells. Additionally, FNC could upregulate multiple phosphorylated kinases in various cell types while downregulating the phosphatases, phosphoribosyl transferases, and deaminases, respectively. The robust phosphorylation capacity of the thymus for cytidine analogue drug FNC, and the activation effect of FNC on the NAs metabolism system potentially contribute to its enrichment in the thymus and immune protection effect. This suggests that it is crucial to consider the expression level of phosphorylation kinases when evaluating NA drug properties, as an important factor during antiviral drug design.

Deep coalbed methane (DCBM), an unconventional gas reservoir, has undergone significant advancements in recent years, sparking a growing interest in assessing pore pressure dynamics within these reservoirs. While some production data analysis techniques have been adapted from conventional oil and gas wells, there remains a gap in the understanding of pore pressure generation and evolution, particularly in wells subjected to large-scale hydraulic fracturing. To address this gap, a novel technique called excess pore pressure analysis (EPPA) has been introduced to the coal seam gas industry for the first time to our knowledge, which employs dual-phase flow principles based on consolidation theory. This technique focuses on the generation and dissipation for excess pore-water pressure (EPWP) and excess pore-gas pressure (EPGP) in stimulated deep coal reservoirs. Equations have been developed respectively and numerical solutions have been provided using the finite element method (FEM). Application of this model to a representative field example reveals that excess pore pressure arises from rapid loading, with overburden weight transferred under undrained condition due to intense hydraulic fracturing, which significantly redistributes the weight-bearing role from the solid coal structure to the injected fluid and liberated gas within artificial pores over a brief timespan. Furthermore, field application indicates that the dissipation of EPWP and EPGP can be actually considered as the process of well production, where methane and water are extracted from deep coalbed methane wells, leading to consolidation for the artificial reservoirs. Moreover, history matching results demonstrate that the excess-pressure model established in this study provides a better explanation for the declining trends observed in both gas and water production curves, compared to conventional practices in coalbed methane reservoir engineering and petroleum engineering. This research not only enhances the understanding of DCBM reservoir behavior but also offers insights applicable to production analysis in other unconventional resources reliant on hydraulic fracturing.

Corrosion-erosion performances of Ti-6.5Al–2Zr–1Mo–1V (TA15) alloy fabricated by two laser additive manufacturing technologies, namely selective laser melting (SLM) and laser metal deposition (LMD) were investigated, and compared with those of traditional forged counterpart. Results show that SLM-ed TA15 possesses better corrosion, wear, and tribocorrosion resistances than LMD-ed and forged TA15. This is mainly attributed to the ultrafine-grain αʹ phase in the microstructure of SLM-ed sample, which improves the hardness and thereby enhances the wear and tribocorrosion resistance. Additionally, the complete αʹ phase formed in SLM-ed sample also avoids the galvanic corrosion that occurs at the α+β-type LMD-ed and forged samples.

Fermentation is a promising approach for improving the utilization of soybean meal (SM) by aquaculture fish, and the strain is the core of microbial fermentation processes. Herein, Pediococcus pentosaceus YC64, an autochthonous probiotic isolated from the intestine of Nile tilapia (Oreochromis niloticus), was applied to the fermentation of raw SM. In an eight-week feeding trial, tilapia juveniles were divided into two treatments fed on diets with 0 % (Control) and 100 % of SM protein replaced by fermented SM (FSM). Results showed that solid-state fermentation improved SM quality indicated by increased acid-soluble protein contents. Fish fed the FSM diet had significantly higher weight gain, feed efficiency, and protein efficiency compared to those fed the SM diet. Furthermore, whole-body protein content significantly increased in the FSM-fed fish, accompanied with the increased amino acid transport and reduced protein catabolism. Texture profile analysis indicated that fish fed the FSM diet had reduced muscle hardness compared with the control, which was associated with changes in collagen deposition and myofiber development. Moreover, feeding an FSM diet enhanced goblet cell proliferation and stimulated mucin secretion, ultimately leading to improved intestinal tight junctions and reduced inflammatory response. Besides, the FSM diet feeding altered intestinal microbiota community, characterized by increased abundance of Pediococcus. Overall, P. pentosaceus YC64 exhibits promise as a fermentation strain in the production of FSM. The FSM performed better than SM in improving the growth performance, feed utilization, and intestine health of Nile tilapia.

Aroma is a key sensory factor in the flavor evaluation of pak choi (Brassica rapa L. ssp. chinensis var. Makino). The pak choi varieties Xiangqingcai (XQC) and Xiuhuajin (XHJ) have unique aroma characteristics, but the chemical profiles of these aromas are unknown. Here, the aroma profiles of three varieties of pak choi including XQC, XHJ, and Suzhouqing (CK, non-aromatic) were determined using gas chromatography–mass spectrometry (GC–MS) and relative odor activity values (rOAV). A total of 15 categories of 716 volatile metabolites were detected in the three pak choi varieties, with terpenoid metabolites identified as the major components, although in each sample the identity of the major terpenoid metabolite varied. There were 53 aroma components in XQC and 54 aroma components in XHJ with rOAV >1, which contribute to rice aroma and fishy odor of these varieties, respectively.

Osteoporotic fractures have become a common public health problem and are usually accompanied by chronic pain. Mg and Mg-based alloys are considered the next-generation orthopedic implants for their excellent osteogenic inductivity, biocompatibility, and biodegradability. However, Mg-based alloy can initiate aberrant activation of osteoclasts and modulate sensory innervation into bone callus resulting in postoperative pain at the sequential stage of osteoporotic fracture healing. Its mechanism is going to be investigated. Strontium hydrogen phosphate (SrHPO4) coating to delay the Mg-based alloy degradation, can reduce the osteoclast formation and inhibit the growth of sensory nerves into bone callus, dorsal root ganglion hyperexcitability, and pain hypersensitivity at the early stage. Liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis of bone marrow-derived macrophages (BMMs) treated with SrHPO4-coated Mg alloy extracts shows the potential effect of increased metabolite levels of AICAR (an activator of the AMPK pathway). We demonstrate a possible modulated secretion of AICAR and osteoclast differentiation from BMMs, which inhibits sensory innervation and postoperative pain through the AMPK/mTORc1/S6K pathway. Importantly, supplementing with AICAR in Mg-activated osteoclasts attenuates postoperative pain. These results suggest that Mg-induced postoperative pain is related to the osteoclastogenesis and sensory innervation at the early stage in the osteoporotic fractures and the SrHPO4 coating on Mg-based alloys can reduce the pain by upregulating AICAR secretion from BMMs or preosteoclasts.

Hydrogen energy, due to its clean and efficient nature, has shown great potential during the current transition period in the shipbuilding industry. However, the application of hydrogen energy in ship energy systems is influenced by variations in operational load and the integration of new energy sources during actual navigation. To address these issues, this paper focuses on optimizing and scheduling the operation of ships under various navigation conditions, considering the distributed nature of hydrogen energy. System simulations were conducted to model the photovoltaic (PV), proton exchange membrane fuel cells (PEMFCs), lithium batteries (LIBs), electrolytic cells (ECs), and energy storage modules of yacht energy systems. Component boundaries and objective functions were set, and two cases (excess photovoltaic state and constant power state) were designed to optimize and regulate the energy balance of hydrogen-powered yachts, enhancing their comprehensive utilization of renewable energy. By comparing the changes in ship energy under the two cases, it was concluded that case 1 ensures the maximum utilization of renewable energy. When photovoltaic power generation is insufficient, the PEMFC and LIB in the system provide the required power to achieve a supply-demand balance. Moreover, when PV power generation is sufficient, hydrogen energy is used to store renewable energy. The optimization method designed in this study can, to some extent, maximize the application of renewable energy in new energy yachts, ensuring the efficiency of the comprehensive energy system of new energy yachts, reducing emissions, and improving the sustainability and economic efficiency of the ships.

This study assessed the service efficacy of Nanjing’s urban open space (UOS) system, emphasizing the complex structural characteristics of UOS services, specifically, the impact of interactions between different subsystems on the overall service efficacy of the UOS system. The objective was to understand whether and how a UOS system can effectively and efficiently meet urban needs under constrained conditions. The dimensions of UOS services and the interrelationships between services offered by different subsystems were examined, and a structural model for assessing the service efficacy of the UOS system was developed. A multidimensional analytical approach was applied to quantify and characterize the relationships between subsystems and identify and determine the weighting of subsystem analysis indicators. The findings indicate that subsystems and their respective indicators differ in importance across dimensions, influence each other, and collectively form the overall service efficacy of a UOS system. Furthermore, while service efficacy across different administrative districts in Nanjing’s main urban areas generally remains moderate, significant differences in evaluation values exist among districts and subsystems, offering direction for future urban planning and resource allocation. This study offers detailed insights into the efficiency and optimization of UOS services, helping urban planners improve UOSs globally.

The organism's normal physiological function is greatly impacted in a febrile environment, leading to the manifestation of pathological conditions including elevated body temperature, dehydration, gastric bleeding, and spermatogenic dysfunction. Numerous lines of evidence indicate that heat stress significantly impacts the brain's structure and function. Previous studies have demonstrated that both animals and humans experience cognitive impairment as a result of exposure to high temperatures. However, there is a lack of research on the effects of prolonged exposure to high-temperature environments on learning and memory function, as well as the underlying molecular regulatory mechanisms. In this study, we examined the impact of long-term heat stress exposure on spatial memory function in rats and conducted transcriptome sequencing analysis of rat hippocampal tissues to identify the crucial molecular targets affected by prolonged heat stress exposure. It was found that the long-term heat stress impaired rats' spatial memory function due to the pathological damages and apoptosis of hippocampal neurons at the CA3 region, which is accompanied with the decrease of growth hormone level in peripheral blood. RNA sequencing analysis revealed the signaling pathways related to positive regulation of external stimulation response and innate immune response were dramatically affected by heat stress. Among the verified differentially expressed genes, the knockdown of Arhgap36 in neuronal cell line HT22 significantly enhances the cell apoptosis, suggesting the impaired spatial memory induced by long-term heat stress may at least partially be mediated by the dysregulation of Arhgap36 in hippocampal neurons. The uncovered relationship between molecular changes in the hippocampus and behavioral alterations induced by long-term heat stress may offer valuable insights for the development of therapeutic targets and protective drugs to enhance memory function in heat-exposed individuals.

Gastric adenocarcinoma is one of the most death cause cancers worldwide. Metabolomics is an effective approach for investigating the occurrence and progression of cancer and detecting prognostic biomarkers by studying the profiles of small bioactive molecules. To fully decipher the functional roles of the disrupted metabolites that modulate the cellular mechanism of gastric cancer, integrated gene-metabolite association network methods are critical to map the associations between metabolites and genes. In this study, we constructed a knowledge-based gene-metabolite association network of gastric cancer using the dysregulated metabolites and genes between gastric cancer patients and control group. The topological pathway analysis and gene-protein-metabolite-disease association analysis revealed four key gene-metabolite pathways which include eleven metabolites associated with modulated genes. The integrated gene-metabolite association network enables mechanistic investigation and provides a comprehensive overview regarding the investigation of molecular mechanisms of gastric cancer, which facilitates the in-depth understanding of metabolic biomarker roles in gastric cancer.

Background: The efficacy and adeptness of ChatGPT 3.5 and ChatGPT 4.0 in the precise diagnosis and management of conditions like atopic dermatitis and Autoimmune blistering skin diseases (AIBD) remain to be elucidated. So this study examined the accuracy and effectiveness of the ChatGPT responses related to understanding, therapies, and specific cases of these two conditions. Method: Firstly, the responses provided by ChatGPTs to a set of 50 questionnaires underwent evaluation by five distinct dermatologists, with complete adjudication of the third-party reviewer. The comparative analysis included the evaluative efficacy of both ChatGPT3.5 and ChatGPT4.0 against the diagnostic abilities exhibited by three distinct cohorts of qualified clinical professionals. And then, an examination was conducted to assess the diagnostic proficiency of ChatGPT3.5 and ChatGPT4.0 in the context of diagnosing specific instances of skin blistering autoimmune diseases. Results: In assessing the proficiency of ChatGPTs in generating responses related to fundamental knowledge about AD it is noteworthy that both versions of ChatGPTs, despite their lack of specialized training on medical databases, exhibited a commendable capacity to yield solutions that exhibited a substantial degree of concurrence with evidence-based medical information. Accordingly we observed that the performance of ChatGPT-4.0 beyond that of the ChatGPT-3.5. However, it it crucial to emphasize that ChatGPT-4.0 did not show the ability to offer answers surpassing those provided by associate senior, and senior medical professionals. In the assessment designed to determine the proficiency of ChatGPTs in recognizing particular type of AIBD, it is evident that both ChatGPT-4 and ChatGPT-3.5 demonstrated inadequacy in providing responses that are both precise and accurate for each individual occurrence of this skin condition. Conclusion: Both ChatGPT-3.5 and ChatGPT-4.0 satisfactory for addressing fundamental inquiries related to atopic dermatitis, however they prove insufficient for diagnosing AIBD. The progress of ChatGPT in achieving utility within the professional medical domain remains a considerable journey ahead.

Background: Suicide ideation has high prevalence in adolescents, better future time perspective is considered a protective role for anxiety, depression, and suicide ideation. However, the impact of future time perspective on suicide ideation remains unclear, especially when anxiety and depression as mediating roles. Methods: A cross-sectional study of college students was performed in Chongqing, China. There are 851 students enrolled in this study and we distribute questionnaires through the WeChat platform to obtain data in 2023. We conducted Pearson correlation analysis and descriptive statistics. Model 6 in PROCESS 4.0 was used to test the multiple mediating effect. Results: College students who have higher future time perspective are associated with a lower risk of anxiety, depression, and suicide ideation. Future time perspective not only affects suicide ideation directly, but also influence it by means of two mediating pathways: ①depression, the mediation effect is 37.41 %; ②the multiple mediating effects of anxiety and depression with a mediating effect of 29.68 %. Conclusion: Higher future time perspective functions as a protective role in anxiety, depression, and suicide ideation; future time perspective can affect and predict the occurrence of suicide ideation by influencing anxiety and depression in college students. This conclusion will be a novel and insightful part of adolescent mental health research, and provide a new perspective to prevent college students from committing suicide in the future.

Fish counting is crucial in fish farming. Density map-based fish counting methods hold promise for fish counting in high-density scenarios; however, they suffer from ineffective ground truth density map generation. High labeling complexities and disturbance to fish growth during data collection are also challenging to mitigate. To address these issues, LDNet, a versatile network with attention implemented is introduced in this study. An imbalanced Optimal Transport (OT)-based loss function was used to effectively supervise density map generation. Additionally, an Image Manipulation-Based Data Augmentation (IMBDA) strategy was applied to simulate training data from diverse scenarios in fixed viewpoints in order to build a model that is robust to different environmental changes. Leveraging a limited number of training samples, our approach achieved notable performances with an 8.27 MAE, 9.97 RMSE, and 99.01% Accuracy on our self-curated Fish Count-824 dataset. Impressively, our method also demonstrated superior counting performances on both vehicle count datasets CARPK and PURPK+, and Penaeus_1k Penaeus Larvae dataset when only 5%–10% of the training data was used. These outcomes compellingly showcased our proposed approach with a wide applicability potential across various cases. This innovative approach can potentially contribute to aquaculture management and ecological preservation through counting fish accurately.

Fish, acting as the dominant vertebrates in aquatic ecosystems, exhibit strong mobility and complex activity patterns, which make it challenging for the quantitative assessment of fish communities. Previous fieldwork has applied multiple fish sampling devices as well as eDNA technology respectively, with limited studies comparing the reliability, representativity, and applicability of eDNA metabarcoding and traditional sampling methods in investigating fish assemblages across spatiotemporal scales. In this study, we selected Lake Huang (a provincial nature reserve) to compare the eDNA technology and traditional sampling methods (multi-mesh gillnets and accordion-shaped traps) in revealing differences in species composition, α diversity, and β diversity of fish assemblages in both high-water phase and low-water phase. Results showed that eDNA technology detected more fish species and required fewer samples to achieve sufficient sampling compared to traditional methods. Specifically, our results demonstrated significant methodological variations in species composition, with both traditional sampling and eDNA approaches revealing the method-dependent species checklist. In the high-water phase, the eDNA approach recorded significantly lower β diversity (βSOR and βSIM) than traditional sampling methods, which may result from the more homogeneous eDNA water samples triggered by flooding, resulting in lower between-sites variations in fish communities. However, in the low-water phase, eDNA technology reported significantly higher β diversity (βSOR and βSNE) than traditional sampling methods, potentially attributed to the loss of eDNA information as well as heterogeneous eDNA samples accompanied by water receding. In addition, taking advantage of the separated and narrowed habitat in the low-water phase, fish individuals were more easily captured, resulting in a relatively higher Shannon-Wiener index recorded by traditional sampling methods. Based on inconsistency in species composition characterized by two methods, our results exhibited that eDNA technology is more efficient in detecting species, while there was an urgent need to design more sensitive primers, provide more complete reference databases, and popularize more emerging sequencing platforms for the advancement of eDNA technology. Comparing with the fish assemblage diversity identified by traditional sampling methods, our result exhibited the transport of DNA fragments may potentially enlarge the homogenized or heterogeneous fish community characterization influenced by flood pulses.

Background: Oncomelania hupensis (O. hupensis), the unique intermediate host for Schistosoma japonicum, exerts a substantial influence on the risk of schistosomiasis. Being amphibious freshwater snails, the growth, development, and reproductive distribution of O. hupensis are intricately tied to climatic environmental variables. This study aims to predict O. hupensis habitat risks along the Yangtze River in China, considering multiple environmental factors. Methods: Data pertaining to the distribution of O. hupensis, including both presence and absence records, with the Jiangsu section of the Yangtze River basin for the period 2017–2021, were retrieved from the Jiangsu Schistosomiasis Control Information Platform. Ten machine learning algorithms and an ensemble model were used to explore environmental drivers. Three datasets (Snail_CLIM, Snail_TOPO, and Snail_ALL) incorporating climatic and topographic variables were examined for their impact on model accuracy. We conducted validation using the AUC and TSS metrics. Moreover, we utilized the data from the 2022 snail field survey for model external validation. Results: The findings demonstrate that snail_ALL, which incorporates both climatic and topographic variables, exhibits superior performance (ensemble model: sensitivity = 98.000, specificity = 95.960, AUC = 0.994). Among the ten model algorithms, Random Forest (RF) exhibited the highest degree of accuracy and stability (Snail_ALL: AUC = 1.000 ± 0.000, TSS = 0.985 ± 0.005). The key environmental factors affecting snail distribution included the distance to the nearest river, elevation, annual precipitation, and annual average pressure. High-risk areas manifested as two distinct concentrations: downstream of the Luhe District in Nanjing and at the confluence of Zhenjiang and Yangzhou. The results of 2022 field validation showed that over 90 % of the data points for snail breeding sites are concentrated in medium to high-risk areas. Conclusion: By selecting pertinent environmental variables and employing ensemble modeling techniques, we can accurately predict O. hupensis habitats. The resulting risk distribution map for snail habitats not only provides valuable insights but also serves as a guiding tool for targeted monitoring and control measures. The holds particular significance within the contest of the Yangtze River protection and restoration projects.

There is a lack of a systematic understanding of the specific mechanism of action of DL0410 in AD treatment. In this study, the combination of RNA-seq and proteomics was firstly employed to uncover the mechanism of action of DL0410 in APP/PS1 transgenic mice. The results of behavioral tests showed that oral administration of DL0410 for 8 weeks improved memory and cognition of APP/PS1 mice. DL0410 significantly reduced β-amyloid deposition and resulted in significant upregulation of synaptophysin, PSD95 and NMDAR/ CaMKⅡ signaling pathway in the hippocampus and cortex, indicating that DL0410 improved synaptic plasticity in APP/PS1 mice, which agrees with the results of RNA-seq and proteomics. Furthermore, the enrichment results of differentially expressed genes identified by RNA-seq and proteomics demonstrate the potential protective effects of DL0410 against oxidative stress and mitochondrial dysfunction. As expected, DL0410 dose-dependently ameliorated oxidative damage and markedly increased the expression of PGC-1α, TFAM, SOD1 and SOD2. Mitochondrial high-resolution respirometry results revealed that mitochondrial respiratory function was significantly improved in APP/PS1 mice administered with DL0410. In addition, DL0410 treatment reduced oxidative damage, strengthened antioxidant system and improved mitochondrial function in Aβ-induced HT22 cells. Altogether, our findings suggest the potential of DL0410 as a novel candidate for AD treatment.

Accurate locating and counting of litopenaeus vannamei fry can provide substantial support for vannamei fry sales and scientific feeding. However, traditional methods not only require visual observation by experts, but also are time-consuming and labor-intensive, with no guarantee to reach consensus between salesmen and customers. In contrast, more innovative methods require more expensive equipment or are only effective under specific conditions. The small size and high density nature of the shrimp fry makes its counting even more challenging. In this study, a point prediction method for counting and localization of litopenaeus vannamei fry with region-based super-resolution enhancement (PPCL-RSE) is proposed. Through the inclusion of three modules of density partitioning, high-density region expansion and regional super-resolution, the accuracy of fry counting and locating is improved. The model is deployed on a cloud server for convenient fry counting and localization based on images taken by smartphone cameras. To achieve this, we create a dataset called Vannamei-983 which contains images with more than 1,000,000 fry labeled. The proposed method shows accuracies of 99.04 % and 97.71 % in counting and localization of shrimp fry in low- and high-density images, respectively. The excellent model performance also demonstrate the effectiveness of the strategies considered in the study.

Adding an anti-corrosion coating to the surface of magnesium (Mg) alloy is an effective means to improve its corrosion resistance, but it is particularly important to enhance the bonding force between the anti-corrosion coating and the Mg matrix. Epoxy resin coating is considered the most cost-effective approach from an industrial standpoint, while the hindering the wider utilization of Mg alloys with epoxy coating in the realm of engineering materials are due to their insufficient adhesion between Mg matrix and the epoxy coating. Here, we demonstrated a simple method for forming an epoxy resin/mineralized film composite coating. The mineralized products coatings were applied to the surface of Mg-3Nd alloy, via a direct reaction between Mg and 15 wt% Na2CO3 solution. Due to the inherent lamellar structure of alkaline magnesium carbonate mineralization film, the mechanical interlocking between the epoxy resin and the Mg substrate are remarkably strengthened. Therefore, this simple surface treatment method is promising to improve the adhesion between the epoxy resin and the matrix. Moreover, the effects of mineralized products coating on the corrosion resistance of Mg with epoxy coating were researched. It was observed that the corrosion resistance of Mg alloy with composite coatings are significantly enhanced. Such an investigation aims to provide a new method for developing a cost-effective and robust epoxy resin/mineralized film composite coating protection structure of Mg alloys in practical applications.

Synergistically enhancing the erosion and impact resistance of contacts poses a significant challenge for cutting-edge electrical equipment. Fortunately, mollusk shells in nature have evolved effective strategies to construct microstructures with superior erosion and impact resistance. Inspired by the structure of nacre, AgSnO2 contact material with hierarchical architectures has been designed and fabricated. The mechanistic link between microstructural evolution and dynamic erosion is studied through experiments combined with Computational Fluid Dynamics (CFD) and Finite Element Method (FEM) simulations. Results show that the reconstructed SnO2 skeleton endowed with a highly continuous and anisotropic ‘flowering'-like structure forms a continuous interpenetrating network with Ag, optimizing the conductive pathways on the molten pool surface. Additionally, the Ag-rich regions in the deeper layers on both sides of the molten pool offers a stable ‘nutrient-supply’ for the continuous ‘flowering’ reconstruction of the skeleton, exhibiting excellent in-situ self-repairing erosion resistance. Benefiting from this synergistic strategy, this skeleton is reconstructed based on its natural structure, which further disperses the stress and deformation concentration while inhibiting interfacial debonding, thereby reducing the formation of cracks and significantly enhancing the impact resistance. This work is expected to breakthrough erosion and impact resistance in extreme condition electrical contact materials through biomimetic microstructure design.

Background: Aberrant functional connectivity is a hallmark of schizophrenia. The precise nature and mechanism of dysconnectivity in schizophrenia remains unclear, but evidence suggests that dysconnectivity is different in wake versus sleep. Microstate analysis uses electroencephalography (EEG) to investigate large-scale patterns of coordinated brain activity by clustering EEG data into a small set of recurring spatial patterns, or microstates. We hypothesized that this technique would allow us to probe connectivity between brain networks at a fine temporal resolution and uncover previously unknown sleep-specific dysconnectivity. Methods: We studied microstates during sleep in patients with schizophrenia by analyzing high-density EEG sleep data from 114 patients with schizophrenia and 79 control participants. We used a polarity-insensitive k-means analysis to extract a set of 6 microstate topographies. Results: These 6 states included 4 widely reported canonical microstates. In patients and control participants, falling asleep was characterized by a shift from microstates A, B, and C to microstates D, E, and F. Microstate F was decreased in patients during wake, and microstate E was decreased in patients during sleep. The complexity of microstate transitions was greater in patients than control participants during wake, but this reversed during sleep. Conclusions: Our findings reveal behavioral state–dependent patterns of cortical dysconnectivity in schizophrenia. Furthermore, these findings are largely unrelated to previous sleep-related EEG markers of schizophrenia such as decreased sleep spindles. Therefore, these findings are driven by previously undescribed sleep-related pathology in schizophrenia.

Purpose: Individuals with chronic kidney disease (CKD) face an elevated residual risk of cardiovascular events, but the relationship between this residual risk and 1,5-anhydroglucitol (1,5-AG) is uncertain. Our study aimed to examine the effect of 1,5-AG on major adverse cardiovascular events (MACEs) and all-cause mortality in acute coronary syndrome (ACS) individuals. Methods: 1253 ACS participants hospitalized were enrolled at Beijing Hospital between March 2017 and March 2020. All participants were classified into 2 groups based on their eGFR (60 ml/min/1.73 m2). The link between 1,5-AG and adverse outcome was investigated in non-CKD and CKD participants. Results: CKD patients had reduced concentrations of 1,5-AG than those without CKD. Throughout a median follow-up duration of 43 months, 1,5-AG was an autonomous hazard factor for MACEs and all-cause mortality. 1,5-AG

The use of ground source heat pumps (GSHP) in solar greenhouses had the potential to improve energy efficiency and reduce carbon emissions. However, because of the imbalance in cooling and heating applications, there would be an imbalance of heat in the subsoil. A numerical model of GSHP in a tomato growing solar greenhouse was created based on EnergyPlus. Annual energy performance simulations were performed with borehole free cooling, ground source heat pump cooling and heating operation modes. Thermal balance of the subsoil was achieved by adjusting the operating strategies of the three modes. Simulation results showed that the average COP of heating and COP of cooling of GSHP were 4.66 and 5.35 respectively.

Tunneling-based static random-access memory (SRAM) devices have been developed to fulfill the demands of high density and low power, and the performance of SRAMs has also been greatly promoted. However, for a long time, there has not been a silicon based tunneling device with both high peak valley current ratio (PVCR) and practicality, which remains a gap to be filled. Based on the existing work, the current manuscript proposed the concept of a new silicon-based tunneling device, i.e., the silicon cross-coupled gated tunneling diode (Si XTD), which is quite simple in structure and almost completely compatible with mainstream technology. With technology computer aided design (TCAD) simulations, it has been validated that this type of device not only exhibits significant negative-differential-resistance (NDR) behavior with PVCRs up to 106, but also possesses reasonable process margins. Moreover, SPICE simulation showed the great potential of such devices to achieve ultralow-power tunneling-based SRAMs with standby power down to 10−12 W.

Pakchoi (Brassica rapa ssp. chinensis) is cultivated for its high nutritional value; however, the nutritional diversity of different pakchoi cultivars is rarely investigated. Herein, we performed widely targeted metabolic profiling analyses of five popular pakchois. A total of 670 metabolites were detected, which could be divided into 13 categories. The accumulation patterns of main nutritional metabolites among the five pakchois were significantly different and complementary. Moreover, the pakchoi cultivar ‘QYC’ showed quite different metabolomic profiles compared with other pakchois. The Venn diagram showed that the 75 differential metabolites were shared among the comparison groups (‘QYC’ vs. ‘MET’/ ‘NBC’/ ‘PPQ’/ ‘XQC’), of which 52 metabolites were upregulated in ‘QYC’. The phenolic acids had the largest variations between ‘QYC’ and the other pakchoi cultivars. These findings expand metabolomic information on different pakchoi cultivars and further provide new insights into the selection and breeding of excellent pakchoi cultivars.

Consider a simple undirected connected graph G, with D(G) and A(G) representing its degree and adjacency matrices, respectively. Furthermore, L(G)=D(G)−A(G) is the Laplacian matrix of G, and Ht=exp⁡(−tL(G)) is the heat kernel (HK) of G, with t>0 denoting the time variable. For a vertex u∈V(G), the uth element of the diagonal of the HK is defined as Ht(u,u)=(exp⁡(−tL(G)))uu=∑k=0∞((−tL(G))k)uuk!, and HE(G)=∑i=1ne−tλi=∑u=1nHt(u,u) is the HK trace of G, where λ1,λ2,⋯,λn denote the eigenvalues of L(G). This study provides new computational formulas for the HK diagonal entries of graphs using an almost equitable partition and the Schur complement technique. We also provide bounds for the HK trace of the graphs.

Diabetic cardiomyopathy (DCM) is a cardiac microvascular complication caused by metabolic disorders. It is characterized by myocardial remodeling and dysfunction. The pathogenesis of DCM is associated with abnormal cellular metabolism and organelle accumulation. Autophagy is thought to play a key role in the diabetic heart, and a growing body of research suggests that modulating autophagy may be a potential therapeutic strategy for DCM. Here, we have summarized the major signaling pathways involved in the regulation of autophagy in DCM, including Adenosine 5’-monophosphate-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), Forkhead box subfamily O proteins (FOXOs), Sirtuins (SIRTs), and PTEN-inducible kinase 1 (PINK1)/Parkin. Given the significant role of autophagy in DCM, we further identified natural products and chemical drugs as regulators of autophagy in the treatment of DCM. This review may help to better understand the autophagy mechanism of drugs for DCM and promote their clinical application.

ABSTRACT: The development of the avian wing pattern has been the subject of heated debate due to its special shape. The Suppressor of cytokine signaling 2 (SOCS2) gene encodes a negative regulator of growth hormone (GH) signaling and bone growth and is known to be strongly expressed in the third digit of chicken forelimbs. These observations suggest that SOCS2 might regulate the morphology of the avian wing, however, the function of SOCS2 in avian limb development remains unknown. Here, we reexamined SOCS2 expression in successive developmental stages of chicken limb development by in situ hybridization (ISH) and describe extended expression from the posterior of the stypolod to the third digit of the forelimbs. We used the RCAS avian retrovirus to overexpress SOCS2 in the developing chicken limb buds, which resulted in reduced or malformed chicken wings while hindlimbs developed normally. Transcriptome sequencing (mRNA-Seq) revealed changes in expression of genes known to be associated with growth and development in forelimbs with overexpressed SOCS2. This study highlights a pivotal role for SOCS2 during the development of the wing in the chicken and provides new insight into molecular mechanisms regulating avian limb development.

The expansion applications of semiconducting polymer dots (Pdots) among optical nanomaterial field have long posed a challenge for researchers, promoting their intelligent application in multifunctional nano-imaging systems and integrated nanomedicine carriers for diagnosis and treatment. Despite notable progress, several inadequacies still persist in the field of Pdots, including the development of simplified near-infrared (NIR) optical nanoprobes, elucidation of their inherent biological behavior, and integration of information processing and nanotechnology into biomedical applications. This review aims to comprehensively elucidate the current status of Pdots as a classical nanophotonic material by discussing its advantages and limitations in terms of biocompatibility, adaptability to microenvironments in vivo, etc. Multifunctional integration and surface chemistry play crucial roles in realizing the intelligent application of Pdots. Information visualization based on their optical and physicochemical properties is pivotal for achieving detection, sensing, and labeling probes. Therefore, we have refined the underlying mechanisms and constructed multiple comprehensive original mechanism summaries to establish a benchmark. Additionally, we have explored the cross-linking interactions between Pdots and nanomedicine, potential yet complete biological metabolic pathways, future research directions, and innovative solutions for integrating diagnosis and treatment strategies. This review presents the possible expectations and valuable insights for advancing Pdots, specifically from chemical, medical, and photophysical practitioners’ standpoints.

Background & Aims: A high human cytomegalovirus (HCMV) infection rate accompanied by an increased level of bile duct damage is observed in the perinatal period. The possible mechanism was investigated. Methods: A total of 1,120 HCMV-positive and 9,297 HCMV-negative children were recruited, and depending on age, their liver biochemistry profile was compared. Fetal and infant biliary epithelial cells (F-BECs and I-BECs, respectively) were infected with HCMV, and the differences in cells were revealed by proteomic analysis. Protein–protein interactions were examined by coimmunoprecipitation and mass spectrometry analyses. A murine cytomegalovirus (MCMV) infection model was established to assess treatment effects. Results: Perinatal HCMV infection significantly increased the level of bile duct damage. Neonatal BALB/c mice inoculated with MCMV showed obvious inflammation in the portal area with an abnormal bile duct structure. Proteomics analysis showed higher CD14 expression in F-BECs than in I-BECs. CD14 siRNA administration hindered HCMV infection, and CD14-knockout mice showed lower MCMV-induced bile duct damage. HCMV infection upregulated CD55 and poly ADP-ribose polymerase-1 (PARP-1) expression in F-BECs. Coimmunoprecipitation and mass spectrometry analyses revealed formation of the CD14–CD55 complex. siRNA-mediated inhibition of CD55 expression reduced sCD14-promoted HCMV replication in F-BECs. In MCMV-infected mice, anti-mouse CD14 antibody and PARP-1 inhibitor treatment diminished cell death, ameliorated bile duct damage, and reduced mortality. Conclusions: CD14 facilitates perinatal HCMV infection in BECs via CD55, and PARP-1-mediated cell death was detected in perinatal cytomegalovirus-infected BECs. These results provide new insight into the treatment of perinatal HCMV infection with bile duct damage. Impact and implications: Perinatal human cytomegalovirus (HCMV) infection is associated with bile duct damage, but the underlying mechanism is still unknown. We discovered that CD14 expression is increased in biliary epithelial cells during perinatal HCMV infection and facilitates viral entry through CD55. We also detected PARP-1-mediated cell death in perinatal HCMV-infected biliary epithelial cells. We showed that blocking CD14 or inhibiting PARP-1 reduced bile duct damage and mortality in a mouse model of murine cytomegalovirus infection. Our findings provide a new insight into therapeutic strategies for perinatal HCMV infection.

Hydrogen peroxide (H2O2) functions as a signaling molecule in diverse cellular processes. While cells have evolved the capability to detect and manage changes in H2O2 levels, the mechanisms regulating key H2O2-producing enzymes to maintain optimal levels, especially in pancreatic beta cells with notably weak antioxidative defense, remain unclear. We found that the protein EI24 responds to changes in H2O2 concentration and regulates the production of H2O2 by controlling the translation of NOX4, an enzyme that is constitutively active, achieved by recruiting an RNA-binding protein, RTRAF, to the 3′-UTR of Nox4. Depleting EI24 results in RTRAF relocating into the nucleus, releasing the brake on NOX4 translation. The excessive production of H2O2 by liberated NOX4 further suppresses the translation of the key transcription factor MafA, ultimately preventing its binding to the Ins2 gene promoter and subsequent transcription of insulin. Treatment with a specific NOX4 inhibitor or the antioxidant NAC reversed these effects and alleviated the diabetic symptoms in beta-cell specific Ei24-KO mice. This study revealed a new mechanism through which cells regulate oxidative stress at the translational level, involving an ER-tethered RNA-binding protein that controls the expression of the key H2O2-producing enzyme NOX4.

Due to the excessive consumption of fossil fuel resources and the emission of a substantial quantity of CO2 into the environment, it is urgent to develop clean energy solutions. In order to reduce carbon emissions from the source, it is effective approach to convert CO2 into various renewable energy fuels. Inspired by the photosynthesis of green plant, CO2 is converted into clean fuel with the aid of catalysts. Regarding the separation and transfer of photogenerated charge carriers, and inadequate adsorption and activation of CO2 on the surface of catalysts, the current semiconductors utilized in photocatalysis have low efficiency. As a result, the current efficiency of photocatalysts is far from meeting the need for practical industrial demands. MXene materials, for example Ti3C2Tx (9980 S cm−1), have emerged as a promising candidate for CO2 reduction due to the significant number of active sites for functional groups, high conductivity and low defects, large surface areas, and outstanding visible light photoelectronic properties. This review provides a critical overview of the recent progress regarding MXene as a co-catalyst in photocatalytic CO2 reduction systems. We systemically explore the fundamental principles and reaction mechanisms associated with separating and transferring photogenerated charge carriers. Additionally, we investigate the basic properties of MXene as a co-catalyst in the context of CO2 reduction. Furthermore, this review also elucidates the impacts of the microstructure of photocatalysts on enhancing photocatalytic performance. Finally, the challenges and opportunities in using MXene as a co-catalyst for CO2 reduction have been presented to inspire further research in this field.

ABSTRACT: Dairy cows have high incidence of ketosis during perinatal. According to our previous studies, elevated ketone bodies (mainly β-hydroxybutyrate, BHB) in the peripheral blood are believed to contribute to the impairment of neutrophils mobility and directionality thereby contributing to the immunosuppression and further infectious disease secondary to ketosis. However, the specific effect of BHB on the directionality of bovine neutrophils needs further study and the underlying molecular mechanisms are still unclear. According to the concentration of serum BHB, 40 multiparous cows (within 3 wk postpartum) were selected and divided into the control (n = 20, BHB 3.0 mM) group. Blood samples were collected for baseline serum characteristics analysis and neutrophil mobility and directionality detection. Platelet activation factor was used as a chemoattractant in cell migration experiments. Our ex-vivo data showed ketotic cows, compared with control cows, were in a negative energy balance state, and their neutrophils had shorter migration distance, lower migration speed, and impaired migration directionality. Neutrophils from control cows were incubated with 3.0 mM BHB for 6 h in vitro. Similarly, BHB stimulation resulted in impaired mobility and directionality of bovine neutrophils. We further specifically studied the underlying molecular mechanism of BHB regulating neutrophil migration directionality in the present study. Cell division control protein 42 homolog (Cdc42) and Ras-related C3 botulinum toxin substrate 1 (Rac1), 2 key markers in the regulation of migration directionality, were found increased after BHB treatment in their total and activated protein levels while decreasing in their transcription level, suggesting that an imbalance of the protein degradation system may be involved. Interestingly, transmission electron microscopy data revealed a decrease in autophagosome number in neutrophils from ketotic cows. Western blotting data showed the accumulation of sequestosome-1 (p62) protein and a decrease in microtubule-associated protein 1 light chain 3-II (LC3-II) protein abundance after BHB treatment, further confirming that the autophagy flux was inhibited in neutrophils from ketotic cows. Additionally, rapamycin (RAPA), a specific autophagy activator, was used with or without BHB treatment in vitro. Accordingly, the BHB-induced impairment of migration directionality but not mobility was relieved by RAPA. Furthermore, as verified by in vivo experiments, compared with the control cows, the protein abundance of total and activated Cdc42 and Rac1 increased and their mRNA abundance decreased in neutrophils from ketotic cows. Overall, the present study revealed that pathological concentration of BHB impairs neutrophil migration directionality through inhibiting the autophagy-mediated degradation of Cdc42 and Rac1. These findings help explain the immunosuppression caused by ketosis.

In electromagnetic launching systems, arc erosion of rail material, such as Al2O3 dispersion-strengthened copper (ODS-Cu), remains a critical unresolved issue. Here, we report a cold-sprayed CuCrZr–W coating on ODS-Cu exhibiting enhanced arc erosion resistance. The coating was fabricated using a bimodal powder mixture comprising coarse CuCrZr and fine W particles, resulting in a dense structure with an embedded networks of fine W particles along intersplat boundaries. Compared to the ODS-Cu substrate, the CuCrZr–W coating displays superior arc erosion resistance, as evidenced by the reduced arc erosion area and depth, shorter arc duration, lower wielding force, and limited molten Al adhesion during arcing tests. The enhanced performance is attributed to a high density of W/CuCrZr interfaces that effectively disperse arcs, the W particle network that alters the flow path of molten Cu, lowering splashing and evaporation. This work provides valuable insights into developing high-performance, arc erosion-resistant coatings for applications where safeguarding against arc erosion is paramount.

Summary: The African swine fever virus (ASFV) and its variants have induced substantial economic losses in China, prompting a critical need for efficient detection methods. Several PCR-based methods have been developed to discriminate between wild-type ASFV and gene-deleted variants. However, the requirement for sophisticated equipment and skilled operators limits their use in field settings. Here, we developed a CRISPR-Cas12b/Cas13a-based detection assay that can identify ASFV variants with minimal equipment requirements and a short turnaround time. The assay utilizes the distinct DNA/RNA collateral cleavage preferences of Cas12b/Cas13a to detect two amplified targets from multiplex recombinase polymerase amplification (RPA) in a single tube, and the results can be visualized through fluorescent or lateral-flow readouts. When tested with clinical samples in field settings, our assay successfully detected all ASFV-positive samples in less than 60 min. This assay provides a rapid on-site surveillance tool for detecting ASFV and its emerging variants.

We determined RNA spectrum of the human RSK4 (hRSK4) gene (also called RPS6KA6) and identified 29 novel mRNA variants derived from alternative splicing, which, plus the NCBI-documented ones and the five we reported previously, totaled 50 hRSK4 RNAs that, by our bioinformatics analyses, encode 35 hRSK4 protein isoforms of 35–762 amino acids. Many of the mRNAs are bicistronic or tricistronic for hRSK4. The NCBI-normalized NM_014496.5 and the protein it encodes are designated herein as the Wt-1 mRNA and protein, respectively, whereas the NM_001330512.1 and the long protein it encodes are designated as the Wt-2 mRNA and protein, respectively. Many of the mRNA variants responded differently to different situations of stress, including serum starvation, a febrile temperature, treatment with ethanol or ethanol-extracted clove buds (an herbal medicine), whereas the same stressed situation often caused quite different alterations among different mRNA variants in different cell lines. Mosifloxacin, an antibiotics and also a functional inhibitor of hRSK4, could inhibit the expression of certain hRSK4 mRNA variants. The hRSK4 gene likely uses alternative splicing as a handy tool to adapt to different stressed situations, and the mRNA and protein multiplicities may partly explain the incongruous literature on its expression and comports.

The efficient and environmentally friendly air conditioning system plays a vital role in cost reduction and efficiency improvement within the shipping industry. This study focuses on a specific ocean-going container ship equipped with the 8S90ME-C10.2 marine diesel engine as its main propulsion system. Firstly, the cooling load of 149.56 kW and a wet load of 18.04 g/s for the container ship were calculated to determine an energy-efficient and comfortable air conditioning scheme. Secondly, a novel combined system, integrating temperature and humidity solution dehumidification with enhanced transcritical CO2 refrigeration using injection subcooling, was proposed. The regenerator for solution dehumidification and the generator for injection refrigeration utilized the main cylinder liner cooling water as a heat source. Based on the system modeling, numerical simulation, and result validation, comprehensive analyses and quantitative evaluations were conducted to investigate the sensitivity of temperature and humidity regulation parameters, system performance, components exergy efficiency, and economics. Finally, employing a multi-objective optimization algorithm, the optimal operating conditions and corresponding objective functions for the system were obtained: exhaust pressure of 9.43 MPa, regeneration temperature of 91.08 °C, subcooling degree of 19.48 °C, coefficient of refrigeration performance of 3.697, exergy loss of 84.136 kW, and an annual operating cost of $111,300. This combined system exhibits high efficiency, environmental friendliness, and comfort, making it well-suited to handle the fluctuating heat and humidity loads during the ocean-going container ship through varying sea climates.

Uncontrolled inflammatory response is both an intervention target for various diseases, and the design basis for drug delivery strategies. In this work, based on the highly enriched characteristics of M1 type macrophages in local inflammation, we used exosomes derived from bone marrow mesenchymal stem cells (BMSC) as drug carriers, modified with hyaluronic acid (HA) and polyethylene glycol (PEG) to prepare an inflammation targeted and anti-inflammatory treatment nanoplatform (EXs-PH). By targeting M1 macrophages, HA endows EXs-PH with the ability to target inflammation, while PEG reduces the interaction between plasma proteins and exosome membrane proteins, giving the exosomes the ability to circulate within the body for a long time. The results indicate that after HA and PEG (PH) modification, exosomes derived from BMSC (EXs) can effectively enrich in the inflammatory site, achieving precise administration of curcumin (Cur) with anti-inflammatory and repair promoting functions. In vivo experiments on acute and chronic inflammatory models of spinal cord injury (SCI) and rheumatoid arthritis (RA) also showed that PH modified Exs loaded with Cur (Cur@EXs-PH) were more effective in improving the recovery of motor function after lesions. In conclusion, the engineered Cur@EXs-PH we designed, provides a new drug delivery carrier for treating inflammatory diseases.

Summary: The increasing need for improved energy storage devices renders it particularly important that inexpensive electrodes with high capacitance, excellent cycling stability, and environment-friendly characteristics are developed. In this study, a wood-derived carbon@reduced graphene (WRG) conductive precursor with an average conductivity of 15.38 S/m was firstly synthesized. The binder-free WRG-MnO2 electrode was successfully constructed by growing MnO2 onto a WRG under hydrothermal conditions. The asymmetric supercapacitor assembled with the WRG-20MnO2 cathode exhibited excellent electrochemical capacitive behavior with a voltage window of 0–2 V, maximum energy density of 52.3 Wh kg−1, and maximum power density of 1642.7 W kg−1, which is mainly due to the distinctive icicle-shaped structure of the MnO2. Thus, a facile strategy for developing high-performance hierarchical porous carbon electrodes that can be used in supercapacitors was developed herein, which may provide new opportunities to improve the high added value of poplar wood.

Background: The correlation between acute ischemic stroke (AIS) and gut microbiota has opened a promising avenue for improving stroke prognosis through the utilization of specific gut bacterial species. This study aimed to identify gut bacterial species in AIS patients and their correlation with stroke severity, 3-month prognosis, and inflammatory markers. Methods: We enrolled 59 AIS patients (from June 2021 to July 2022) and 31 age-matched controls with similar cerebrovascular risk profiles but no stroke history. Fecal samples were analyzed using 16 S rDNA V3–V4 sequencing to assess α and β diversity and identify significant microbiota differences. AIS cases were categorized based on the National Institute of Health Stroke Scale (NIHSS) scores and 3-month modified Rankin Scale (mRS) scores. Subgroup analyses were performed, and correlation analysis was used to examine associations between flora abundance, inflammatory markers and stroke outcome. Results: Significant differences in β-diversity were observed between case and control groups (P

Excellent electromagnetic wave absorption ability and effective absorption bandwidth have been the development direction of electromagnetic wave absorbing materials. In this paper, a rational structural design is proposed. Graphene oxide (GO)/polyaniline (PANI) layer was formed on the surface of the natural material bamboo powder (BP) by an interfacial polymerization process. The combination of GO and PANI improves the impedance mismatch of the conductive polymer PANI. Enhanced dielectric storage and loss capability of the composite GO/PANI/BP. The addition of BP brings more electromagnetic wave loss channels to the composite GO/PANI/BP. This unique structure facilitates the construction of a three-dimensional electromagnetic wave-reflecting cavity, which improves the absorptive capacity of the composite by introducing effective multiple reflections. The conductivity of GO/PANI/BP was 1.78 (±0.06) S/cm. When filled to 30 wt%, a minimum reflection loss (RLmin) of −44 dB at 9.36 GHz and a thickness of 3 mm, and an effective absorption bandwidth (

Summary: The acidic metabolic byproducts within the tumor microenvironment (TME) hinder T cell effector functions. However, their effects on T cell infiltration remain largely unexplored. Leveraging the comprehensive The Cancer Genome Atlas dataset, we pinpoint 16 genes that correlate with extracellular acidification and establish a metric known as the “tumor acidity (TuAci) score” for individual patients. We consistently observe a negative association between the TuAci score and T lymphocyte score (T score) across various human cancer types. Mechanistically, extracellular acidification significantly impedes T cell motility by suppressing podosome formation. This phenomenon can be attributed to the reduced expression of methyltransferase-like 3 (METTL3) and the modification of RNA N6-methyladenosine (m6A), resulting in a subsequent decrease in the expression of integrin β1 (ITGB1). Importantly, enforced ITGB1 expression leads to enhanced T cell infiltration and improved antitumor activity. Our study suggests that modulating METTL3 activity or boosting ITGB1 expression could augment T cell infiltration within the acidic TME, thereby improving the efficacy of cell therapy.

Objectives: This study aimed to explore the potential of full dynamic PET kinetic analysis in assessing amyloid binding and perfusion in the cardiac region using 18F-Florbetapir PET, establishing a quantitative approach in the clinical assessment of cardiac amyloidosis disease. Materials & methods: The distribution volume ratios (DVRs) and the relative transport rate constant (R1), were estimated by a pseudo-simplified reference tissue model (pSRTM2) and pseudo-Logan plot (pLogan plot) with kidney reference for the region of interest-based and voxel-wise-based analyses. The parametric images generated using the pSRTM2 and linear regression with spatially constrained (LRSC) algorithm were then evaluated. Semi-quantitative analyses include standardized uptake value ratios at the early phase (SUVREP, 0.5–5 min) and late phase (SUVRLP, 50–60 min) were also calculated. Results: Ten participants [7 healthy controls (HC) and 3 cardiac amyloidosis (CA) subjects] underwent a 60-min dynamic 18F-Florbetapir PET scan. The DVRs estimated from pSRTM2 and Logan plot were significantly increased (HC vs CA; DVRpSRTM2: 0.95 ± 0.11 vs 2.77 ± 0.42, t’(2.13) = 7.39, P = 0.015; DVRLogan: 0.80 ± 0.12 vs 2.90 ± 0.55, t’(2.08) = 6.56, P = 0.020), and R1 were remarkably decreased in CA groups, as compared to HCs (HC vs CA; 1.08 ± 0.37 vs 0.56 ± 0.10, t’(7.63) = 3.38, P = 0.010). The SUVREP and SUVRLP were highly correlated to R1 (r = 0.97, P

Mangroves are an essential component of coastal ecosystems. Accurate and effective identification and extraction of mangrove areas from remote sensing imagery is crucial for monitoring changes in the nearshore ecological environment. High-resolution remote sensing imagery is often difficult or expensive to obtain and usually lacks sufficient temporal coverage, so most monitoring of mangrove forests still relies on medium- or low-resolution imagery, resulting in inaccurate distribution of extracted mangrove areas. The super-resolution (SR) images generated by increasingly widely used deep learning (DL) models may be an alternative. To validate this, we evaluated the extraction of mangroves from SR images generated by four DL models (i.e., enhanced super-resolution generative adversarial networks (ESRGAN), Real-ESRGAN, vast-receptive-field pixel attention network (VapSR), and image restoration methods using swin transformer (SwinIR)). The models were trained on paired (high-resolution) Chinese GF-1 satellite images and (low-resolution) Landsat 8 datasets. The performance of model fitting, vegetation indices, and extracted mangrove areas was evaluated using three commonly used classifiers (i.e., support vector machines (SVM), random forest (RF), and gradient-boosted decision tree (GBDT)) in combination with ground-truth sampling points and public mangrove datasets. Results showed that: (1) the SR images generated by DL-based models can facilitate the extraction of mangrove features. (2) The quality evaluation metrics peak signal-to-noise ratio (PSNR) and structural similarity index measurements (SSIM) cannot be regarded as absolute criteria for SR images, especially when the SR images were used for mangrove feature extractions. (3) The SR image generated by the VapSR model was best suited for extracting mangrove forests and performed even better than the original high-resolution images. (4) Taking a public dataset as a benchmark, the mangrove areas extracted from the SR image generated by the VapSR model were closer to the benchmark than the original Landsat-8 and GF-1. Overall, the DL-based SR models can enhance mangrove extractions and potentially have widespread applications.

Endometriosis is a disease characterized by the ectopic growth of endometrial tissue (glands and stroma) outside the confines of the uterus and often involves vital organs such as the intestines and urinary system. Endometriosis is considered a refractory disease owing to its enigmatic etiology, propensity for recurrence following conservative or surgical interventions, and the absence of radical treatment and long-term management. In recent years, the incidence of endometriosis has gradually increased, rendering it a pressing concern among women of childbearing age. A more profound understanding of its pathogenesis can significantly improve prognosis. Recent research endeavors have spotlighted the molecular mechanisms by which microRNAs (miRNAs) regulate the occurrence and progression of endometriosis. Many miRNAs have been reported to be aberrantly expressed in the affected tissues of both patients and animal models. These miRNAs actively participate in the regulation of inflammatory reactions, cellular proliferation, angiogenesis, and tissue remodeling. Their capacity to modulate crucial signaling pathways, such as the Wnt/β-catenin signaling pathway, reinforces their potential utility as diagnostic markers or therapeutic agents for endometriosis. In this review, we provide the latest insights into the role of miRNAs that interact with the Wnt/β-catenin pathway to regulate the biological behaviors of endometriosis cells and disease-related symptoms, such as pain and infertility. We hope that this review will provide novel insights and promising targets for innovative therapies addressing endometriosis.

ABSTRACT: Ketosis is often accompanied by a reduction in milk production in dairy cows, but the molecular mechanism has not been fully elucidated. Ketotic cows possess systemic oxidative stress (OS), which may implicate apoptosis in mammary glands. Sirtuin 3 (SIRT3) is a vital regulator of cellular redox homeostasis and is under the control of AMP-activated protein kinase (AMPK) signaling in nonruminants. Thus, we aimed to investigate (1) the AMPK-SIRT3 and apoptosis status of mammary glands from ketotic cows, (2) the effect of SIRT3 on OS-induced apoptosis in bovine mammary epithelial cells (BMEC), and (3) the role of AMPK signaling on SIRT3-mediated effects on apoptosis. Mammary gland samples were reused from a previous study, which contained healthy and ketotic cows (both n = 15). BMEC were incubated with 0, 0.3, 0.6, or 0.9 mM H2O2 for 6 h with/without a 30 min incubation of an antioxidant MitoQ (1 μM). Then BMEC were incubated with SIRT3 overexpression adenovirus (Ad-SIRT3) for 6 h followed by a 6 h incubation with 0.6 mM H2O2. Finally, BMEC were treated with the AMPK inhibitor Compound C (Cd C,10 μM) for 30 min before the H2O2 challenge, or cells were initially treated with the AMPK agonist MK8722 (10 μM) for 30 min followed by a 30-h culture with/without si-SIRT3 and eventually the H2O2 exposure. Ketotic cows displayed higher levels of Bax, Caspase-3 and Bax/Bcl-2 but lower levels of Bcl-2 in mammary glands. H2O2 incubation displayed similar results, exhibiting a dose-dependent manner between the H2O2 concentration and the apoptosis degree. Mito Q pretreatment reduced cellular reactive oxygen species and rescued cells from apoptosis. Ketotic cows had a lower mammary protein abundance of SIRT3. Similarly, H2O2 incubation downregulated both mRNA and protein levels of SIRT3 in a dose- and time-dependent manner. Ad-SIRT3 infection lowered levels of cellular reactive oxygen species, Bax, Caspase-3 and Bax/Bcl-2 but increased levels of Bcl-2. TUNEL assays confirmed that Ad-SIRT3 infection mitigated H2O2-induced apoptosis. Both ketotic cows and H2O2-induced BMEC had lower levels of p-AMPK and p-AMPK/AMPK. Additionally, Cd C pretreatment decreased SIRT3 and Bcl-2 expression but increased levels of Bax and Caspase-3. Contrary to the inhibitor, MK8722 had opposite effects and reduced the percentage of apoptotic cells. However, these effects of MK8722 were reversed upon SIRT3 silencing. In conclusion, in vivo data confirmed that ketosis is associated with greater apoptosis and restricted AMPK-SIRT3 signaling in mammary glands; in vitro data indicated that SIRT3 mitigates OS-induced apoptosis via AMPK signaling. As such, there may be potential benefits for targeting the AMPK-SIRT3 axis to help counteract the negative effects of mammary glands during ketosis.

Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells. The all-hydrocarbon peptide stapling technique has already widely adopted with great success, yielding numerous potent peptide-based molecules. Based on our prior efforts, we conceived and prepared a double-stapled peptide in this study, termed FRNC-1, which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β. The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form. Additionally, FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized (OVX) mice after intravenous injection and importantly, after oral (intragastric) administration. The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis (PMOP).

The emerging energy technologies, such as wind energy and photovoltaic (PV), will gradually replace the traditional synchronous generator in wide-area power system. As the wind, PV and energy storage equipment are all controlled by power electronic inverters, which are decoupled from the system and cannot provide effective inertial support to the power system with new energy (PS-NE), resulting in stability problems caused by the low inertia of the PS-NE. In particular, this paper investigates the inertia response of synchronous generator and PS-NE, and the inertia model of PS-NE considering with high renewable penetrations. Then the relation between inertia and frequency of PS-NE with high renewable penetrations are explored in this paper. Besides, the real-time inertia of the PS-NE is estimated by using the statistical algorithm based on the historical data of the PS-NE, and the range of the inertia and synchronous generator start-up capacity of the PS-NE can be estimated by using the statistical algorithm based on the renewable penetrations when we cannot obtain the historical data of the PS-NE. In addition, IEEE39 system of PS-NE is used to verify the relation between inertia and frequency of PS-NE with high renewable penetrations, and the inertia estimation of PS-NE with high renewable penetrations is analyzed in this paper.

As the development of photovoltaic (PV) power generation continuously accelerated the total installed capacity of PV, the traditional static load model is difficult to meet the needs of the power grid with the increasing penetration of PV. And the dynamic model of grid-connected PV power generation is complicated and there are plenty parameters need to be identified, so the dynamic model of grid-connected PV power generation are extremely challenging to apply in wide-area power system. In this paper, a discrete-time equivalent model of PV (PDEM) is established based on the third-order dynamic differential equation of the PV power generation system and the parameters of the PDEM are identified using the least squares (LS) and the bat algorithm (BA). Besides, the dynamic characteristics of the PV power generation grid connected system with different permeability and the fitting residuals of the two methods is analyzed in the IEEE14-bus system incorporated into the PV system. The applicability of the PDEM is verified by setting short circuit grounding fault and changing the PV permeability and voltage dip. The simulation results demonstrate that the PDEM has a strong adaptability and good applicability in the case of high PV permeability with a wide application. And the applicability of the BA in identification of PDEM are given in this paper.

Background: Acetaldehyde dehydrogenase (ALDH) is a common oxidoreductase and one of the aldehyde dehydrogenases, which can convert toxic acetaldehyde to harmless acetyl CoA. Results: A novel acetaldehyde dehydrogenase (LpALDH) from Lactiplantibacillus plantarum was obtained by gene mining and then was analyzed by a series of bioinformatics software. Phylogenetic tree results showed that LpALDH was highly homologous with acetaldehyde dehydrogenase derived from Pediococcus sp., and their sequence similarity was 62.9%. Moreover, it was successfully expressed in Escherichia coli BL21, its expression level was 195 U/mL, which was about 600 times than that expressed in L. plantarum. After purification by affinity chromatography, the specific activity of reLpALDH was 1709 U/mg. Its temperature optimum was 35°C, and the optimal reaction pH was 8.0. Moreover, the purified LpALDH showed good stability in simulated gastrointestinal fluids, which indicated that it had great potential in functional food additive field. Conclusions: This research also laid a solid foundation for further molecular modification, optimal expression host selection and application of acetaldehyde dehydrogenases.How to cite: Wang Z, He J, Liu X, et al. High-level expression of an acetaldehyde dehydrogenase from Lactiplantibacillus plantarum and preliminary evaluation of its potential as a functional food additive. Electron J Biotechnol 2023;63. https://doi.org/10.1016/j.ejbt.2022.12.005.