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Abstract Skin cancer is a common disease resulting from genetic defects, and early detection is critical to improve treatment outcomes. Diagnostic programs that use computer aid especially those that use supervised learning are very useful in early diagnosis of skin cancer. This research therefore presents a new approach that integrates optimization methods with supervised learning to improve skin cancer diagnosis using machine vision approach. The presented method is initiated by data pre-processing that involves the removal of unnecessary data. Then, to segment the images, a combination of K-means clustering and social spider optimization technique is employed. The region of interest is then extracted from the segmented image and from this region a convolutional neural network extracts the significant features. To enhance the classification performance as compared with the standard classifiers, this research introduces a new concept of error correcting output codes coupled with a weighted Hamming distance in the group of gamma classifiers. The ability of the proposed approach in segmentation of skin lesions and classifying them was tested using samples from the ISIC-2017 and ISIC-2016 databases. The introduced method obtained state-of-the-art accuracy on both datasets (ISIC-2016: 97.10%, ISIC-2017: 95.17%). In particularly, the accuracy of the introduced approach for both these databases is at least 1.17% higher than the compared methods. This proves the high performance of the suggested method based on the usage of the convolutional neural networks for feature extraction and gamma classifiers with error correcting output codes for classification in skin cancer detection.

Abstract The existing deep estimation networks often overlook the issue of computational efficiency while pursuing high accuracy. This paper proposes a lightweight self-supervised network that combines convolutional neural networks (CNN) and Transformers as the feature extraction and encoding layers for images, enabling the network to capture both local geometric and global semantic features for depth estimation. First, depth-separable convolution is used to construct a dilated convolution residual module based on a shallow network to improve the shallow CNN feature extraction receptive field. In the transformer, a multidepth separable convolution head transposed attention module is proposed to reduce the computational burden of spatial self-attention. In the feedforward network, a two-step gating mechanism is proposed to improve the nonlinear representation ability of the feedforward network. Finally, the CNN and transformer are integrated to implement a depth estimation network with a local-global context interaction function. Compared with other lightweight models, this model has fewer model parameters and higher estimation accuracy. It also has better generalizability for different outdoor datasets. Additionally, the inference speed can reach 87 FPS, achieving better real-time performance and accounting for both inference speed and estimation accuracy.

The phases, microstructure, and mechanical properties of Si-alloyed (Ti28Zr40Al20Nb12)100-xSix (x = 1, 3, 5, 10) high entropy alloys are studied. Although silicides were not detected in the as-cast 1 at. % Si-alloyed sample, after annealing all the four alloys have the same phase composition: the Zr5Al3-type phase, Zr5Si3-type silicides, and the BCC/B2 dual-phase matrix, indicating that 1 at. % Si addition is adequate for the formation of silicides in equilibrium. The phase morphologies show a dependence on the Si content and the cooling rate, which changed from the occurrence of columnar grain zones together with coarse dendrites of the as-cast 1 at. % Si-alloyed alloy to four different cooling-rate-related morphologies in the other three as-cast alloys. After heat treatment, differently shaped precipitates tend to aggregate and spherize, and a three-step-shaped phase morphology is observed when the Si content is above 5 at. %. All precipitates are rich in Zr due to either the strong Si–Zr pair or Al–Zr pair, but heterogeneous distributions of Si and Al exist. An increase of the Si content led to a gradual decrease of the compressive strength in both as-cast and annealed samples, yet the total fracture strain does not show monotonously decrease trend. 5 at. % Si-alloyed samples possessed a higher total fracture strain than the 3 at. % Si-alloyed samples.

Abstract Nucleoli are fundamentally essential sites for ribosome biogenesis in cells and formed by liquid-liquid phase separation (LLPS) for a multilayer condensate structure. How the nucleoli integrity is maintained remains poorly understood. Here, we reveal that METTL3/METTL14, the typical methyltransferase complex catalyzing N6-methyladnosine (m6A) on mRNAs maintain nucleoli integrity in human embryonic stem cells (hESCs). METTL3/METTL14 deficiency impairs nucleoli and leads to the complete loss of self-renewal in hESCs. We further show that SUV39H1/H2 protein, the methyltransferases catalyzing H3K9me3 were dramatically elevated in METTL3/METTL14 deficient cells, which causes an accumulation and infiltration of H3K9me3 across the whole nucleolus and impairs the LLPS. Mechanistically, METTL3/METTL14 complex serves as an essential adapter for CRL4 E3 ubiquitin ligase targeting SUV39H1/H2 for polyubiquitination and proteasomal degradation and therefore prevents H3K9me3 accumulation in nucleoli. Together, these findings uncover a previously unknown role of METTL3/METTL14 to maintain nucleoli integrity by facilitating SUV39H1/H2 degradation in human cells.

Abstract Lymphocyte decline, particularly the depletion of NK cells, is a prominent feature of immunosuppression following severe tissue injury, heightening the susceptibility of severe trauma patients to life-threatening infections. Previous research indicates that the reduction in the number of NK cells is closely associated with the process of cell death. Nonetheless, the precise mechanism of NK cell death remains unknown. Here, we discovered that following severe traumatic injury, NK cells undergo several cell death pathways, dominated by apoptosis and pyroptosis with coexistence of necrotic cell death, immunogenic cell death, ferroptosis, and autophagy. These NK cells with different paradigms of death have diverse cytokine expression profiles and diverse interactions with other immune cells. Further exploration revealed that hypoxia was strongly associated with this diverse paradigm of NK cell death. Detailed investigation of paradigms of cell death may help to enhance comprehension of lymphopenia post-severe trauma, to develop new strategy in preventing immunosuppression, and then to improve outcome for severe trauma population.

Abstract Heptafluoroisobutyronitrile (C4F7N) is being considered as a promising alternative to the greenhouse gas SF6 in the electrical industry. However, its biotoxicity necessitates the development of gas sensing technology to detect leaked C4F7N. A combination of density functional theory and experiments was employed to evaluate the adsorption and sensing performance of different metal‐phthalocyanines as potential sensing materials for C4F7N detection. The study included exploring adsorption configurations with adsorption energies, electron transfer, and adsorption distance, as well as comparisons of electronic properties, electron distribution, and density of states (DOS) among the MPcs. Furthermore, gas sensing experiments were conducted using different MPcs to detect 25–100 ppm C4F7N. The results revealed that Mn‐Pc, Fe‐Pc, Co‐Pc, and Zn‐Pc exhibited considerable chemical interactions, while Ni‐Pc and Cu‐Pc showed weaker adsorption strength. These findings were further elucidated based on the electron density and DOS of atomic orbitals. Moreover, gas sensing experiments indicated that Co‐Pc demonstrated a higher response compared to Fe‐Pc at the same concentration of C4F7N. Overall, the theoretical and experimental insights offer valuable guidance for C4F7N detection and provide a systematic approach to screen and explore organometallic polymer‐based gas sensors applicable in various fields.

Abstract Objectives To evaluate the diagnostic accuracy of liver dual-layer spectral-detector CT (SDCT) derived parameters of liver parenchyma for grading steatosis with reference to magnetic resonance imaging-based proton density fat fraction (MRI-PDFF). Methods Altogether, 320 consecutive subjects who underwent MRI-PDFF and liver SDCT examinations were recruited and prospectively enrolled from four Chinese hospital centers. Participants were classified into normal (n = 152), mild steatosis (n = 110), and moderate/severe(mod/sev) steatosis (n = 58) groups based on MRI-PDFF. SDCT liver parameters were evaluated using conventional polychromatic CT images (CTpoly), virtual mono-energetic images at 40 keV (CT40kev), the slope of the spectral attenuation curve (λ), the effective atomic number (Zeff), and liver to spleen attenuation ratio (L/S ratio). Linearity between SDCT liver parameters and MRI-PDFF was examined using Spearman correlation. Cutoff values for SDCT liver parameters in determining steatosis grades were identified using the area under the receiver-operating characteristic curve analyses. Results SDCT liver parameters demonstrated a strong correlation with PDFF, particularly Zeff (rs = −0.856; p

Ultraviolet (UV) radiation poses risks to both human health and organics. In response to the urgent demand for UV-shielding across various applications, extensive endeavors have been dedicated to developing UV-shielding materials spanning from wide-bandgap semiconductors to organo-inorganic composite films. However, existing UV shielding materials, though suitable for daily use, cannot meet the demands of extreme conditions. In this work, we incorporated CeO2 as a UV absorber into Y2O3 transparent ceramics for UV-shielding. The effect of CeO2 concentration on the optical, mechanical, and thermal properties of Y2O3 ceramics was systematically investigated. These findings indicate that CeO2 serves not only as a UV absorber but also as an effective sintering aid for Y2O3 transparent ceramics. The 5 at% Ce-doped Y2O3 transparent ceramics exhibit the optimal optical quality, with in-line transmittance of ~77% at 800 nm. The introduction of Ce shifted the UV cutoff edge of Y2O3 transparent ceramics from 250 to 375 nm, which was attributed to the visible band absorption of Ce4+. This shift grants UV shielding capabilities to Y2O3 transparent ceramics, resulting in 100% shielding for ultraviolet C (UVC, 100–280 nm) and ultraviolet B (UVB, 280–320 nm) and ~95% shielding for ultraviolet A (UVA, 320–400 nm). The service stability (optical properties) under various corrosive conditions (acid, alkali, UV irradiation, and high temperature) was investigated, confirming the excellent stability of this transparent ceramic UV-shielding material. A comparison of the performance parameters of transparent ceramics with those of traditional UV shielding materials such as glasses, films, and coatings was conducted. Our work provides innovative design concepts and an effective solution for UV-shielding materials for extreme conditions.

Abstract Background The undergraduate tutorial system (UTS) is a crucial measure in China for adhering to the principle of prioritizing foundational education, innovating the undergraduate talent training mode, and building a powerful country of higher education. This study investigated undergraduate students’ satisfaction with UTS and the influencing factors, aiming to promote the healthy and sustainable development of UTS and provide practical implications and suggestions for universities. Methods Based on relevant theories, we conducted a survey study and leveraged structural equation modeling to assess students’ satisfaction with UTS and explore the influencing factors. Results Our Pearson correlation analysis showed that students’ satisfaction with mentors was positively correlated with dimensions such as humanistic care (r = 0.844, P

Abstract Vertically stacked all-organic active-matrix organic light-emitting diodes are promising candidates for high-quality skin-like displays due to their high aperture ratio, extreme mechanical flexibility, and low-temperature processing ability. However, these displays suffer from process interferences when interconnecting functional layers made of all-organic materials. To overcome this challenge, we present an innovative integration strategy called “discrete preparation-multilayer lamination” based on microelectronic processes. In this strategy, each functional layer was prepared separately on different substrates to avoid chemical and physical damage caused by process interferences. A single interconnect layer was introduced between each vertically stacked functional layer to ensure mechanical compatibility and interconnection. Compared to the previously reported layer-by-layer preparation method, the proposed method eliminates the need for tedious protection via barrier and pixel-defining layer processing steps. Additionally, based on active-matrix display, this strategy allows multiple pixels to collectively display a pattern of “1” with an aperture ratio of 83%. Moreover, the average mobility of full-photolithographic organic thin-film transistors was 1.04 cm2 V−1 s− 1, ensuring stable and uniform displays. This strategy forms the basis for the construction of vertically stacked active-matrix displays, which should facilitate the commercial development of skin-like displays in wearable electronics.

Abstract The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.

Hot cracking is the most prevalent defect in the rapid solidification process of alloys, which seriously restricts the mechanical properties of the build. Solidification shrinkage is one of the key factors leading to hot cracking sensitivity, and it, together with tensile stress, causes pressure drops inside the liquid channel. However, the mechanism of solidification shrinkage on hot cracking is not clear. In this work, we established a non-equilibrium phase field model considering the density change during liquid-solid phase transformation. The effects of solidification shrinkage on the morphology and solute segregation of liquid channel in directional solidification were simulated by examples with different solid density. The solidification shrinkage will promote the release and diffusion of solute, leading to an increase in the proportion of high solute concentration liquid in the channel. The columnar dendrites continue to solidify, leading to a decrease in constitutional supercooling in the channel, thereby reducing the temperature at which the solid skeletons connect with each other. This results in the channel becoming narrow and elongated, increasing the hot cracking sensitivity. Finally, the solidification curves obtained from the phase field model and analytical model are input into the RDG (Rappaz, Drezet and Gremaud) model to predict the pressure drop in the system. The numerical results indicate that the maximum pressure drop in the channel occurs at the root and increases with solidification shrinkage. These results demonstrate that the phase field model, which takes into account the change of liquid-solid densities during phase transition, can accurately analyze the impact of solidification shrinkage on hot cracking sensitivity and the maximum pressure drop in the liquid channel.

Abstract In recent years, clear aligner can enhance individual appearance with dental defects, so it used more and more widely. However, in manufacturing process, there are still some problems, such as low degree of automation and high equipment cost. The problem of coordinate system mismatch between gingival curve point cloud and dental CAD model is faced to. The PCA-ICP registration algorithm is proposed, which includes coarse match algorithm and improve-ICP registration algorithm. The principal component analysis (PCA) based method can roughly find the posture relationship between the two point clouds. Using z-level dynamic hierarchical, the ICP registration can accurately find the posture between these two clouds. The final registration maximum distance error is 0.03 mm, which is smaller than robot machining error. Secondly, the clear aligner machining process is conducted to verify the registration effectiveness. Before machining, the path is generated based on the well registered gingival curve. After full registration, the tool path is calculated by establishing a local coordinate system between the workpiece and the tool to avoid interference. This path is calculated and generated as an executable program for ABB industrial robots. Finally, the robot was used for flexible cutting of clear aligners and was able to extract products, ensuring the effectiveness of the proposed research. This method can effectively solve the limitations of traditional milling path planning under such complex conditions.

Abstract Systemic Immune Inflammatory Index (SII) is a novel indicator of inflammation. However, no studies have reported the effect of SII on the association between metals and total fat (TOFAT). We aim to investigate the mediated effect of SII on the relationship between urinary metals and TOFAT in a US adult population. This cross-sectional study was conducted among adults with complete information on SII, urine metal concentrations, and TOFAT from the 2011–2018 National Health and Nutrition Examination Survey (NHANES). Multifactorial logistic regression and restricted cubic splines were used to explore the association between urine metal levels and TOFAT. Furthermore, serial mediation analyses were used to investigate the mediating effect of SII on metals and TOFAT. A total of 3324 subjects were included in this study. After adjusting for confounders, arsenic (As), cadmium (Cd), cobalt (Co), cesium (Cs), inorganic mercury (Hg), molybdenum (Mo), manganese (Mn), lead (Pb), antimony (Sb), and thallium(Tl) had negative decreased trends of odds ratios for TOFAT (all P for trend

Abstract The bidirectional migration of halides and silver causes irreversible chemical corrosion to the electrodes and perovskite layer, affecting long-term operation stability of perovskite solar cells. Here we propose a silver coordination-induced n-doping of [6,6]-phenyl-C61-butyric acid methyl ester strategy to safeguard Ag electrode against corrosion and impede the migration of iodine within the PSCs. Meanwhile, the coordination between DCBP and silver induces n-doping in the PCBM layer, accelerating electron extraction from the perovskite layer. The resultant PSCs demonstrate an efficiency of 26.03% (certified 25.51%) with a minimal non-radiative voltage loss of 126 mV. The PCE of resulting devices retain 95% of their initial value after 2500 h of continuous maximum power point tracking under one-sun irradiation, and > 90% of their initial value even after 1500 h of accelerated aging at 85 °C and 85% relative humidity.

Abstract Background The restoration of cerebrovascular regulation and improvement of cerebral blood flow in ischaemic regions are crucial for improving the clinical prognosis after stroke. An-Gong-Niu-Huang-Wan (AGNHW) is a famous traditional compound Chinese medicine that has been used for over 220 years to treat acute ischaemic stroke; however, its role in the regulation of cerebral blood flow is still unclear. The aim of the present study was to investigate the regulatory effect of AGNHW on cerebral blood flow and microcirculation after ischaemic stroke and to elucidate the underlying mechanisms involved. Methods Male C57BL/6 mice were subjected to distal middle cerebral artery occlusion (dMCAO) and randomly assigned to the sham, MCAO, or AGNHW groups. AGNHW was administered intragastrically 1 h after dMCAO. The rotarod test was utilized to evaluate behavioural function; TTC was used to determine the infarct volume; and ischaemic injury was assessed by detecting brain levels of SOD, MDA and NO. Then, cortical perfusion and acetazolamide-induced cerebrovascular reactivity were assessed using laser speckle contrast imaging, and the velocity and flux of red blood cells in cortical capillaries were detected using two-photon laser scanning microscopy. In addition, we employed RNA-Seq to identify variations in gene expression profiles and assessed endothelium-dependent changes in microcirculatory dysfunction by measuring vasoactive mediator levels. Results AGNHW significantly increased cerebral blood flow, reduced the infarct volume, and promoted functional recovery after cerebral ischaemia. AGNHW increased the velocity and flux of red blood cells in capillaries and improved cerebrovascular reactivity in the ischaemic cortex. Furthermore, AGNHW regulated endothelium-dependent microcirculation, as evidenced by decreases in the expression of endothelins (Edn1, Edn3 and Ednrb) and the ratios of brain and serum TXB2/6-keto-PGF1α and ET-1/CGRP. Conclusions AGNHW improved cerebral hypoperfusion, regulated cerebrovascular reactivity and attenuated microcirculatory dysfunction within the ischaemic cortex after stroke. This outstanding effect was achieved by modulating the expression of genes related to vascular endothelial cell function and regulating endothelium-dependent vasoactive mediators.

Bacterial infection hampers wound repair by impeding the healing process. Concurrently, inflammation at the wound site triggers the production of reactive oxygen species (ROS), causing oxidative stress and damage to proteins and cells. This can lead to chronic wounds, posing severe risks. Therefore, eliminating bacterial infection and reducing ROS levels are crucial for effective wound healing. Nanozymes, possessing enzyme-like catalytic activity, can convert endogenous substances into highly toxic substances, such as ROS, to combat bacteria and biofilms without inducing drug resistance. However, the current nanozyme model with single enzyme activity falls short of meeting the complex requirements of antimicrobial therapy. Thus, developing nanozymes with multiple enzymatic activities is essential. Herein, we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles (Ru-PC NPs) with diverse enzymatic activities to aid wound healing and combat bacterial infections. Under acidic conditions, due to their glutathione (GSH) depletion and peroxidase (POD)-like activity, Ru-PC NPs combined with H2O2 exhibit excellent antibacterial effects. However, in a neutral environment, the Ru-PC NPs, with catalase (CAT) activity, decompose H2O2 to O2, alleviating hypoxia and ensuring a sufficient oxygen supply. Furthermore, Ru-PC NPs possess exceptional antioxidant capacity through their superior superoxide dismutase (SOD) enzyme activity, effectively scavenging excess ROS and reactive nitrogen species (RNS) in a neutral environment. This maintains the balance of the antioxidant system and prevents inflammation. Ru-PC NPs also promote the polarization of macrophages from M1 to M2, facilitating wound healing. More importantly, Ru-PC NPs show good biosafety with negligible toxicity. In vivo wound infection models have confirmed the efficacy of Ru-PC NPs in inhibiting bacterial infection and promoting wound healing. The focus of this work highlights the quadruple enzymatic activity of Ru-PC NPs and its potential to reduce inflammation and promote bacteria-infected wound healing.

Abstract The emerging wearable skin-like electronics require the ultra-flexible organic transistor to operate at low voltage for electrical safety and energy efficiency and simultaneously enable high field-effect mobility to ensure the carrier migration ability and the switching speed of circuits. However, the currently reported low-voltage organic transistors generally present low mobility, originating from the trade-off between molecular polarity and surface polarity of the dielectrics. In this work, the orientation polarization of the dielectric is enhanced by introducing a flexible quaternary ammonium side chain, and the surface polarity is weakened by the shielding effect of the nonpolar methyl groups on the polar nitrogen atom. The resulting antisolvent QPSU dielectric enables the high-dielectric constant up to 18.8 and the low surface polarity with the polar component of surface energy only at 2.09 mJ/m2. Such a synergistic polarization engineering between orientation polarization and surface polarity makes the solution-processed ultraflexible transistors present the ultralow operational voltage down to −3 V, the ultrahigh charge-carrier mobility up to 8.28 cm2 V−1 s−1 at 1 Hz, excellent cyclic operational stability and long-term air stability. These results combined with the ultrathin thickness of transistor as low as 135 nm, the ultralight mass of 0.5 g/m2, the conformal adherence capability on human skin and 1-μm blade edge, and the strong mechanical robustness with stable electrical properties for 30,000 bending cycles, open up an available strategy to successfully realize low-voltage high-mobility solution-processed organic transistor, and presents the potential application of QPSU dielectric for the next-generation wearable imperceptible skin-like electronics.

Nuclear power is essential for sustainable energy infrastructure and economic development, necessitating materials for high-radiation environments that can facilitate visualization and observation. Conventional lead glass is inadequate for future requirements due to radiation-induced darkening, poor mechanical properties, and toxicity. Therefore, there is urgent to find new window materials that offer multi-ionization shielding (particularly against deep-penetrating gamma ray, γ, and neutron, n, radiations), desirable opto-mechanical properties, service stability against darkening, and non-toxicity. In this study, we report a family of transparent rare-earth pyrochlore ceramics LaxGd2−xZr2O7, offering unique chemo-physical properties that are ideal for robust radiation shielding windows. Remarkably, we demonstrated the capability of maintaining high transparency under heavy-dose exposure to 1000 ​kGy 60Co γ radiation. We observed the service stability against radiation darkening can be greatly enhanced with La-rich compositions, while Gd-rich compositions undergo shallow darkening that can be reversibly recovered under visible light. This behavior is attributed to mitigated oxygen migration from 48f to 8a in La-rich compositions, which have high pyrochlore phase stability and well-ordered atomic structures, and reversible oxygen migration between 48f and 8a in Gd-rich compositions, which remain active at room temperature. Our proposal and demonstration unlock ample opportunities in designing functional transparent ceramics as window materials for demanding applications in high-radiation environments.

IntroductionIschemic stroke is a leading cause of morbidity and mortality in older adults. Therefore, in this study, we sought to understand the interplay between the microbiota, gut, and brain in the context of stroke in older adults.ObjectiveTo determine whether gut microbiota from younger individuals promotes recovery through angiogenesis in both elderly stroke patients and aged stroke mice, we explored the changes in gut microbiota and the correlation between short-chain fatty acids (SCFAs) and angiogenesis in the aged stroke population. Then, we altered the gut microbiome in aged mice by transplanting microbiota from younger donors before inducing experimental stroke to explore the mechanism by which gut microbiota-derived SCFAs promote angiogenesis.MethodsPart I: We conducted a single-center, double-blind trial to compare gut microbiota diversity and SCFA levels in fecal samples from older stroke patients with those from younger stroke patients. Additionally, we measured levels of vascular endothelial growth factor (VEGF) and VEGFC levels in plasma to assess their correlation with SCFA levels. Part II: We performed fecal microbiota transplantation (FMT) 3 days before inducing ischemic stroke in aged male mice (16–18) via distal middle cerebral artery occlusion (dMCAO). The FMT was conducted using gut microbiomes from either young donors (2–3 months) or aged donors (16–18 months).ResultsIn older stroke patients, gut microbiota diversity was significantly reduced compared to that in younger stroke patients. Furthermore, levels of acetate, a bacterially derived SCFA, were lower and positively correlated with angiogenesis markers (VEGF and VEGF-C). In aged stroke mice, transplantation of young microbiota improved stroke outcomes by promoting angiogenesis, which was facilitated by lymphatic ingrowth into the cortex. This protective effect was linked to gut microbiota-derived acetate, which enhanced lymphangiogenesis by replenishing acetyl coenzyme A.Conclusions(a) Gut microbiota-derived acetate promotes angiogenesis post-stroke and (b) lymphatic ingrowth into the cerebral cortex was observed in post-dMCAO mice. These findings suggest that selectively promoting SCFA-producing bacteria, particularly acetate-producers, could be a promising therapeutic strategy to reduce functional impairments in older stroke subjects.

IntroductionThe successful outcome of a pregnancy depends on the proper functioning uterine epithelium. DNA damage binding protein 1 and cullin 4-associated factor 2 (DCAF2), a conserved substrate receptor for the cullin 4-RING E3 ubiquitin ligase (CRL4) complex, is essential for maintaining genome stability by facilitating ubiquitin-mediated degradation of substrates.MethodsTo better understand the physiological role of DCAF2 in female reproduction, we conducted a study using mice with conditional knockout (cKO) of DCAF2 in the uterus using the progesterone receptor Cre (PgrCre/+) mouse model.ResultsOur results showed the cKO mice were completely infertile, despite having ovarian function. The cKO mice exhibited severely thin uteri, demonstrating notable defects in both the uterine epithelium and a lack of glands. In addition, there were impaired proliferation and differentiation of epithelial cells in the cKO mice, ultimately resulting in failed implantation. Moreover, through deciphering the uterine transcriptome of cKO mice, we revealed crucial differentially expressed genes associated with steroid signaling. Further experiments have demonstrated cKO mice exhibit elevated uterine PGR signaling and reduced estrogen receptor signaling, although the levels of progesterone and estrogen remained unaltered. These alterations may contribute to defects in epithelium.DiscussionOverall, our findings highlight a previously unrecognized but indispensable role for DCAF2 in the development of uterine luminal and glandular epithelium by orchestrating PGR and estrogen receptor responses. Its deficiency in the uterus leads to mouse infertility.

BackgroundAcute pancreatitis (AP) is an extraintestinal manifestation of inflammatory bowel disease (IBD). Numerous observational studies have reported an increased risk of AP in patients diagnosed with IBD. However, the causal association and directionality between IBD or its subtypes and the development of AP remains unclear due to the limitations of observational research. This study aims to explore the relationship between IBD or its subtypes and AP risk using Mendelian Randomization (MR) method.MethodsA two-sample bidirectional MR study was conducted, selecting genetic variants associated with IBD and AP as instrumental variables from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) and FinnGen databases, respectively. The inverse-variance weighted (IVW) method used as the primary approach for causal inference. The Cochran Q test was employed for heterogeneity assessment. Sensitivity analyses were performed using the MR Egger intercept test, MR-Presso, and Leave-one-out method.ResultsThe results revealed that IBD (OR = 1.049, 95% CI = 1.010–1.090, p = 0.013) and ulcerative colitis (UC) (OR = 1.057, 95% CI = 1.013–1.102, p = 0.011) were significantly associated with an increased risk of AP. However, Crohn’s disease (CD) (OR = 1.023, 95% CI = 0.993-1.055, p = 0.134) did not show a causal association with the risk of AP. Interestingly, AP was suggestively associated with a decreased risk of CD (OR = 0.797, 95% CI = 0.637-0.997, p = 0.047). Furthermore, there was no causal association between AP and the risk of IBD (OR = 0.886, 95% CI = 0.753-1.042, p = 0.144) or UC (OR = 0.947, 95% CI = 0.773-1.159, p = 0.595).ConclusionIn conclusion, this study provides genetic evidence supporting the causal influence of IBD (specifically UC) on AP, while CD does not appear to have a causal impact on AP.

Abstract Light‐triggered synaptic plasticity (LTSP) induced by electron trapping in organic photoelectric synaptic transistors (OPSTs) offers potential prospects in neuromorphic wearable artificial intelligence. However, a consistent and universal comprehend for LTSP behaviors especially on oxygen effect in OPSTs is still a critical challenge hindering their practical applications. A mechanism on strong dependency between the oxygen‐induced and polar‐group electron trapping in OPSTs, is successfully unveiled in this study for the first time. And the interaction between the oxygen and polar dielectric interface can be enhanced by properly modulating the specific surface area of thin‐film semiconductors. This effectively binds the oxygen near conducting channel and further improves the trapping efficiency for photogenerated electrons, undergoing the time‐dependent photocurrent generation and subsequent prolonged decay, forming the typical LTSP behaviors. These experimental demonstrations differ from previous reports and therefore may contribute an innovative perspective in the design of functional layers for high‐performance OPST devices.

ABSTRACT This study aims to explore the link between retinal vein occlusion (RVO), a blinding ocular condition, and alterations in gut microbiota composition, to offer insights into the pathogenesis of RVO. Fecal samples from 25 RVO patients and 11 non-RVO individuals were analyzed using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS). Significant differences in the abundance of gut microbial species were noted between RVO and non-RVO groups. At the phylum level, the RVO group showed an elevation in the ratio of Firmicutes to Bacteroidetes. At the genus level, the RVO group showed higher abundance in Escherichia_Shigella (P < 0.05) and less abundance in Parabacteroides (P < 0.01) than the non-RVO group. Functional predictions indicated reduced folate synthesis, biotin metabolism, and oxidative phosphorylation, with an increase in butyric acid metabolism in the RVO group. LC-MS analysis showed significant differences in purine metabolism, ABC transporters, and naphthalene degradation pathways, especially purine metabolism. Pearson correlation analysis revealed significant associations between bacterial genera and fecal metabolites. Enrichment analysis highlighted connections between specific metabolites and bacterial genera. The findings showed that the dysregulation of gut microbiota was observed in RVO patients, suggesting the gut microbiota as a potential therapeutic target. Modulating the gut microbiota could be a novel strategy for managing RVO and improving patient outcomes. Furthermore, the study findings suggest the involvement of gut microbial dysbiosis in RVO development, underscoring the significance of understanding its pathogenesis for effective treatment development.IMPORTANCERetinal vein occlusion (RVO) is a blinding ocular condition, and understanding its pathogenesis is crucial for developing effective treatments. This study demonstrates significant differences in gut microbiota composition between RVO patients and non-RVO individuals, implicating the involvement of gut microbial dysbiosis in RVO development. Functional predictions and metabolic profiling provide insights into the underlying mechanisms, highlighting potential pathways for therapeutic intervention. These findings suggest that modulating the gut microbiota might be a promising strategy for managing RVO and improving patient outcomes.

T-2 toxin is one of trichothecene mycotoxins, which can impair appetite and decrease food intake. However, the specific mechanisms for T-2 toxin-induced anorexia are not fully clarified. Multiple research results had shown that gut microbiota have a significant effect on appetite regulation. Hence, this study purposed to explore the potential interactions of the gut microbiota and appetite regulate factors in anorexia induced by T-2 toxin. The study divided the mice into control group (CG, 0 mg/kg BW T-2 toxin) and T-2 toxin-treated group (TG, 1 mg/kg BW T-2 toxin), which oral gavage for 4 weeks, to construct a subacute T-2 toxin poisoning mouse model. This data proved that T-2 toxin was able to induce an anorexia in mice by increased the contents of gastrointestinal hormones (CCK, GIP, GLP-1 and PYY), neurotransmitters (5-HT and SP), as well as pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in serum of mice. T-2 toxin disturbed the composition of gut microbiota, especially, Faecalibaculum and Allobaculum, which was positively correlated with CCK, GLP-1, 5-HT, IL-1β, IL-6 and TNF-α, which played a certain role in regulating host appetite. In conclusion, gut microbiota changes (especially an increase in the abundance of Faecalibaculum and Allobaculum) promote the upregulation of gastrointestinal hormones, neurotransmitters, and pro-inflammatory cytokines, which may be a potential mechanism of T-2 toxin-induced anorexia.

In order to improve the production of coalbed methane vertical wells in the central and northern Zhengzhuang block, southern Qinshui Basin, Shanxi, China, this paper analyzes the reasons for the poor stimulation effect of medium-deep coalbed methane vertical wells, based on the ground stress test data and fracturing monitoring data of these evaluation wells in the study area, proposes targeted stimulation techniques, designs and carries out field comparative pilot studies and analyzes their results. The results show that there are three main reasons for the low production of these vertical wells in the study area. Firstly, the vertical fracture is dominant, resulting in the shorter length of hydraulic fractures. With the increase of burial depth, the length and width of fractures decreases at the same fracturing scale. Secondly, with the increase of burial depth, the embedment depth of proppants into coal rock increases and the closure of hydraulic fractures speeds up. As a result, the stable production time is short, and the main form of gas production curve is “single peak” type. Thirdly, after the initial fracturing, the coal body structure is much more broken, and new fractures are easy to enter the initial fractures, which increases the difficulty of creating new fractures, resulting in poor stimulation effect. In view of the above reasons, the paper proposes an innovative technology of pre-plug, large-scale and remote-support re-fracturing. Pre-plug means that relatively low displacement, sand ratio and scale are first used to fill initial fractures, and then large-scale re-fracturing is carried out to create new fractures. Large-scale fracturing refers to the fracturing with large displacement, large fluid volume and high sand ratio. In order to improve the stimulation effect of middle-deep reservoirs, the fracturing fluid volume is increased from 600−800 m3 to more than 1 300−2 000 m3, the displacement is increased from 6−8 m3/min to more than 10−14 m3/min, and a low viscosity fracturing fluid system combined with low density proppants is used to increase the sand ratio from 7%−8% to more than 10%−15%. Remote-support is a combination of self-suspended proppants and large displacement to increase proppants migration distance and increase the proportion of the propped fractures. The average daily production of a single well reached 1 380 m3, which was 1 190 m3 higher than that before, and nearly 1 000 m3 higher than the stable gas production of adjacent wells, realizing the production breakthrough of vertical wells in the low-production area of the middle-deep reservoir in the north of Zhengzhuang block. Results of the comparative pilot studies showed that the average net construction pressure increased by 3.3 MPa after pre-plug, compared with the initial fracturing, which means that new fractures were formed and resulted in the production increase by 1 000 m3 compared with that of the wells without the Pre-plug. The pilot results show that, in general, the larger the technical parameters of pre-plug, large-scale and remote-support re-fracturing, the better the production performance.

BackgroundPulmonary fibrosis currently lacks screening and diagnostic methods in the early stages and effective treatments in the later stages, so there is an urgent need to explore the mechanisms and develop targeted treatments.ObjectiveTo screen the expression of differentially expressed circular RNA (circRNA) hsa_circUCK2 under pathological conditions and to explore its effect on pulmonary fibrosis.MethodsIn the cell-based experiments, hsa_circUCK2 was knocked down in HPF-a cells using small interfering RNA (siRNA), and HPF-a cells were stimulated by TGF-β1. Four groups were set up: si-NC group, si-circUCK2 group, si-NC+TGF-β1-treated group, and si-circUCK2+TGF-β1-treated group. Western blot assay was used to detect the expression of fibronectin (FN1) in HPF-a cells of the four groups, scratch assay was used to detect the migration ability of HPF-a cells, and CCK-8 assay was used to detect the proliferation ability of HPF-a cells in the two groups with TGF-β1 stimulation, the si-NC+TGF-β1-treated group and the si-circUCK2+TGF-β1-treated group. In the animal experiments, forty-eighty healthy SPF-grade male C57BL/6 mice were randomly divided into four groups: saline+si-con group, saline+si-circ_0000115 group, SiO2+si-con group, and SiO2+si-circ_0000115 group. Mouse lung circRNA mmu_circ_0000115 (mouse homolog of hsa_circUCK2) was knocked down by tracheal drip injection of siRNA, and a mouse lung fibrosis model was constructed by tracheal drip injection of SiO2 suspension (0.2 g·kg−1, 50 mg·mL−1) after 48 h. Real-time fluorescence quantitative PCR was used to detect the knockout efficiency in each organ of the mouse, Western blot was applied to detect the expression of type I collagen α2 (COL1A2) in the lung tissues, and Sirius red was used to detect collagen synthesis in the lung tissues.ResultsIn the cell-based experiments, after the knockdown of hsa_circUCK2, the Western blot results showed that the expression level of the FN1 protein in TGF-β1-stimulated HPF-a cells was significantly down-regulated (P

Abstract Background Isatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs. Results Here we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield—980.8 mg/L of isatropolone A—achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date. Conclusion In Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A.

The mode-division multiplexing technique combined with a few-mode erbium-doped fiber amplifier (FM-EDFA) demonstrates significant potential for solving the capacity limitation of standard single-mode fiber (SSMF) transmission systems. However, the differential mode gain (DMG) arising in the FM-EDFA fundamentally limits its transmission capacity and length. Herein, an innovative DMG equalization strategy using femtosecond laser micromachining to adjust the refractive index (RI) is presented. Variable mode-dependent attenuations can be achieved according to the DMG profile of the FM-EDFA, enabling DMG equalization. To validate the proposed strategy, DMG equalization of the commonly used FM-EDFA configuration was investigated. Simulation results revealed that by optimizing both the length and RI modulation depth of the femtosecond laser-tailoring area, the maximum DMG (DMGmax) among the 3 linear-polarized (LP) mode-group was mitigated from 10 dB to 1.52 dB, whereas the average DMG (DMGave) over the C-band was reduced from 8.95 dB to 0.78 dB. Finally, a 2-LP mode-group DMG equalizer was experimentally demonstrated, resulting in a reduction of the DMGmax from 2.09 dB to 0.46 dB, and a reduction of DMGave over the C band from 1.64 dB to 0.26 dB, with only a 1.8 dB insertion loss. Moreover, a maximum range of variable DMG equalization was achieved with 5.4 dB, satisfying the requirements of the most commonly used 2-LP mode-group amplification scenarios.

For the technical problem of low intelligence in the process of drilling and pressure relief in high stress mines, the research status of pressure relief technology and equipment at home and abroad is summarized and analyzed in this study. It is pointed out that the development of high-performance, highly reliable, and efficient fully autonomous drilling system of anti-impact drilling robot is an important development direction to solve the problem of rock burst prevention and control. To this end, the five key technologies that affect the performance of the drilling system, namely “the precise recognition of hole position, the precise perception of drilling tool posture, the wireless electromagnetic intelligent detection, the intelligent recognition of drilling tool operation status, and the precise control of the drilling system” have been summarized, and the solutions and methods have been provided. In response to the problem of accurate identification of pressure relief holes in complex and harsh environments, a SinGAN model for pressure relief hole image sample expansion is developed, which integrates image size adjustment and multi-stage training modes. The Faster RCNN optimized by multi-layer feature fusion is introduced, and a hole position recognition model based on an improved SqueezeNet lightweight network architecture is constructed to achieve an accurate and fast recognition of pressure relief hole positions. To address the issue of precise perception of drilling tool posture, the unscented Kalman filter optimized by improved gradient descent algorithm is designed for the initial alignment of Inertial Measurement Unit (IMU). Multiple IMU spatial array layouts are designed, and a BP neural network-based compensation method for drilling tool posture error is studied, aiming to improve the accuracy of drilling tool posture calculation and achieve a precise drilling pressure relief. Aiming at the precise detection of drilling conditions in complex geological environments, a wireless elec-tromagnetic transmission system architecture for underground measurement while drilling in coal mines has been established. The principles of adaptive modulation of weak electromagnetic wave signals and high-speed bidirec-tional electromagnetic transmission technology have been explored, and the measurement principles and imple-mentation processes of geological parameters, geological parameters, and engineering parameters at the bottom of the hole have been investigated. To address the issue of identifying the operational status of drilling systems, a multi-domain feature extraction architecture for drilling signals in the time domain, frequency domain, and time frequency domain, as well as a deep network advanced feature extraction architecture, have been constructed. In addition, the key component health status assessment and fault diagnosis techniques for drilling systems have been proposed, and a prediction model for sticking risk factors based on an improved bat optimized long-term and short-term memory network has been built to accurately predict the stuck status of pressure relief drilling tools. In terms of the issue of precise control of drilling systems, the working principle of the hydraulic system of the drilling system is analyzed, and a precise control scheme for the drilling system considering the characteristics of coal and rock is formulated. The principle of solving the optimal control parameters of the drilling system based on torque and position is explored, aiming to achieve intelligent collaborative control and parallel operation of the drilling return system and feed system.

Abstract Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance is the bottleneck in ovarian cancer treatment. The increasing use of novel drugs in clinical practice poses challenges for the treatment of drug-resistant ovarian cancer. Continuing to classify drug resistance according to drug type without understanding the underlying mechanisms is unsuitable for current clinical practice. We reviewed the literature regarding various drug resistance mechanisms in ovarian cancer and found that the main resistance mechanisms are as follows: abnormalities in transmembrane transport, alterations in DNA damage repair, dysregulation of cancer-associated signaling pathways, and epigenetic modifications. DNA methylation, histone modifications and noncoding RNA activity, three key classes of epigenetic modifications, constitute pivotal mechanisms of drug resistance. One drug can have multiple resistance mechanisms. Moreover, common chemotherapies and targeted drugs may have cross (overlapping) resistance mechanisms. MicroRNAs (miRNAs) can interfere with and thus regulate the abovementioned pathways. A subclass of miRNAs, “epi-miRNAs”, can modulate epigenetic regulators to impact therapeutic responses. Thus, we also reviewed the regulatory influence of miRNAs on resistance mechanisms. Moreover, we summarized recent phase I/II clinical trials of novel drugs for ovarian cancer based on the abovementioned resistance mechanisms. A multitude of new therapies are under evaluation, and the preliminary results are encouraging. This review provides new insight into the classification of drug resistance mechanisms in ovarian cancer and may facilitate in the successful treatment of resistant ovarian cancer.

Abstract Background The causal association between gut microbiome and HIV infection remains to be elucidated. We conducted a two-sample mendelian randomization analysis to estimate the causality between gut microbiome and HIV infection. Methods Publicly released genome-wide association studies summary data were collected to perform the mendelian analysis. The GWAS summary data of gut microbiome was retrieved from the MiBioGen consortium, which contains 18 340 samples from 24 cohorts. GWAS summary data of HIV infection was collected from the R5 release of FinnGen consortium, including 357 HIV infected cases and 218 435 controls. The SNPs were selected as instrumental variables according to our selection rules. And SNPs with a F-statistics less than ten were regarded as weak instrumental variables and excluded. Mendelian randomization analysis was conducted by five methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. The Cochran’s Q test and MR-Egger intercept test were performed to identify heterogeneity and pleiotropy. Leave-one-out analysis were used to test the sensitivity of the results. Results Fifteen gut microbiota taxa showed causal effects on HIV infection according to the MR methods. Four taxa were observed to increase the risk of HIV infection, including Ruminococcaceae (OR: 2.468[1.043, 5.842], P: 0.039), Ruminococcaceae UCG005 (OR: 2.051[1.048, 4.011], P: 0.036), Subdoligranulum (OR: 3.957[1.762, 8.887], P < 0.001) and Victivallis (OR: 1.605[1.012, 2.547], P=0.044). Erysipelotrichaceae was protective factor of HIV infection (OR: 0.278[0.106, 0.731], P < 0.001) and Methanobrevibacter was also found to be associated with reduced risk of HIV infection (OR: 0.509[0.265, 0.980], P=0.043). Horizontal pleiotropy was found for Fusicatenibacter (P

Abstract Aims/Introduction To evaluate the relative contributions of the area under the C‐peptide curve (AUCC) in diabetic retinopathy (DR) during an oral glucose tolerance test and C‐peptide release test in patients with type 2 diabetes. Materials and Methods We retrospectively analyzed the data of 969 patients. Their general characteristics were retrieved. A series of parameters for assessing pancreatic β‐cells function, such as the AUCC for six time periods: 0–60 min (AUCC0–60), 0–120 min (AUCC0–120), 0–180 min (AUCC0–180), 60–120 min (AUCC60–120), 60–180 min (AUCC60–180) and 120–180 min (AUCC120–180); the area under the glucose‐time curve for six time periods: 0–60 min (AUCG0–60), 0–120 min (AUCG0–120), 0–180 min (AUCG0–180), 60–120 min (AUCG60–120), 60–180 min (AUCG60–180) and 120–180 min (AUCG120–180) and their related indexes, were calculated through 0–180 min oral glucose tolerance test and C‐peptide release test. We used univariate analysis to examine the potential factors affecting DR. Spearman's correlation was used to analyze the correlation between AUCC‐related indexes and DR. The logistic regression model was used to investigate AUCC and its related indexes’ contribution to incidence DR. A smooth curve fitting model was used to determine the correlation, non‐linear relationship, and threshold effect between AUCC and DR. Results Of the 969 patients with type 2 diabetes, 469 (48.40%) and 500 (51.60%) were classified as the DR group and non‐DR group. Compared with the non‐DR group, the DR patients had lower AUCC and AUCC/AUCG. Spearman's correlation analysis showed that AUCC‐related indexes were all negatively correlated with DR. The logistic regression analysis determined that there were associations between AUCC and DR in the adjusted models. The odds ratio values of AUCC0–60, AUCC0–120, AUCC0–180, AUCC0–60/AUCG0–60, AUCC0–120/AUCG0–120, AUCC0–180/AUCG0–180, AUCC60–120, AUCC60–180, AUCC120–180, AUCC60–120/AUCG60–120, AUCC60–180/AUCG60–180 and AUCC120–180/AUCG120–180 were 0.817 (0.750, 0.890), 0.925 (0.895, 0.955), 0.951 (0.932, 0.970), 0.143 (0.060, 0.340), 0.194 (0.093, 0.406), 0.223 (0.116, 0.427), 0.886 (0.842, 0.933), 0.939 (0.915, 0.963), 0.887 (0.846, 0.930), 0.253 (0.133, 0.479), 0.282 (0.160, 0.497) and 0.355 (0.220, 0.573), respectively. AUCC showed a non‐linear relationship with DR, with an inflection point. The inflection points of AUCC180/AUCG180, AUCC60–120, AUCC60–180, AUCC120–180, AUCC60–120/AUCG60–120, AUCC60–180/AUCG60–180, AUCC120–180/AUCG120–180 and DR were 17.51, 0.542, 6.6, 15.7, 8.23, 0.534, 0.593 and 0.808 (P

In order to further improve the development effect of coalbed methane wells, a variety of seismic attributes of the target coal seam are extracted, and production distribution samples of developed wells are established. On this basis, through the fitting analysis of all seismic attributes and yield samples, the index weight method is used to calculate that the cumulative contribution rate of coherence and root mean square amplitude to yield is more than 85%, so the two seismic attributes of coherence and root mean square amplitude are selected. Finally, through the fitting correlation coefficient between the two attributes and the yield, the comprehensive attribute prediction formula was established, and the favorable development units were divided. The correlation between forecast results and developed well production is enhanced. The results show that development units can be accurately divided through well data and seismic attribute optimization technology.

The southern Qinshui Basin is rich in coalbed methane resources, but the geological and engineering conditions are complex, the adaptability of Fanzhuang mature technology popularization in neighboring areas is poor, and the development of coalbed methane scale benefits faces severe challenges. In order to solve the problems of coalbed methane in the southern Qinshui Basin, such as “difficult well location deployment, long drilling cycle, easy collapse of naked eye wells, and low single well production”, a number of key technologies such as integrated geological engineering technology have been carried out, and a number of key technologies have been formed, such as “three properties” coal reservoir evaluation, controllable horizontal well drilling and completion, segmented fracturing, and dredging-type drainage, and field tests and promotion have been carried out. The research results show that through the organic combination of geology and engineering, the geological model provides technical support for engineering technology optimization, and engineering practice continuously corrects the geological model to improve the accuracy; the coal seam drilling rate of horizontal well is 95%, the drilling complexity of single well is reduced by 40% on average, the production capacity reaches 90%, and the average daily production of single well is more than 8 000 m3.

Abstract Photothermal therapy (PTT) is a cancer-targeted treatment approach.The occurrence of tumors may be related to microbial infections (Viruses, bacteria, fungi, etc.), which probably provokes anti-tumor immunity. However, T cells in the context of cancer become exhausted and dysfunctional. Galectin-9 (Gal-9) is highly expressed in normal tissues and associates with body immune tolerance, and was firstly evidenced with much higher expression on the primary solid tumors than CD80/86 (B7) and CD274 (PD-L1) here, which suggests that Gal-9 may be a key factor in inhibiting the anti-tumor immunity, and its receptor T cell immunoglobulin and mucin domain 3 (TIM-3) was discovered on the cytotoxic T lymphocytes (CTL) with high expression as well based on the single cell analysis. The immune checkpoint communications showed that the Gal-9/TIM-3 axis played the most vital role on negatively regulating the anti-tumor immunity of CTL for melanoma. Then, we used a novel transdermal photothermal nanosensitizer (FSGG) loading Gal-9 siRNA (FSGG/siGal-9) for knocking the tumor cells down Gal-9 to block the Gal-9/TIM-3 axis and prohibit CTL exhaustion synergizing PTT against melanoma, which evidenced good effects on inhibiting tumor growth and enhancing anti-tumor immunity, named “photothermal immunotherapy”. This paper provides a new perspective for tumor prevention and treatment.

Intratumoral microbiota can regulate the tumor immune microenvironment (TIME) and mediate tumor prognosis by promoting inflammatory response or inhibiting anti-tumor effects. Recent studies have elucidated the potential role of local tumor microbiota in the development and progression of lung adenocarcinoma (LUAD). However, whether intratumoral microbes are involved in the TIME that mediates the prognosis of LUAD remains unknown. Here, we obtained the matched tumor microbiome and host transcriptome and survival data of 478 patients with LUAD in The Cancer Genome Atlas (TCGA). Machine learning models based on immune cell marker genes can predict 1- to 5-year survival with relative accuracy. Patients were stratified into high- and low-survival-risk groups based on immune cell marker genes, with significant differences in intratumoral microbial communities. Specifically, patients in the high-risk group had significantly higher alpha diversity (p < 0.05) and were characterized by an enrichment of lung cancer-related genera such as Streptococcus. However, network analysis highlighted a more active pattern of dominant bacteria and immune cell crosstalk in TIME in the low-risk group compared to the high-risk group. Our study demonstrated that intratumoral microbiota-immune crosstalk was strongly associated with prognosis in LUAD patients, which would provide new targets for the development of precise therapeutic strategies.

Efforts to enhance wheat quality without compromising yield are imperative in the context of climate change. However, the quantification of management measures that simultaneously elevate wheat protein concentration, especially its components, while maintaining yield has been scarcely addressed due to its inherent complexity. In this study, we investigated the impact of various combinations of sowing dates, nitrogen fertilizer, and irrigation on improving the protein concentration of strong gluten winter wheat (Jimai 20) using a validated wheat grain protein component simulation model in Tai'an, Shandong. Our results indicate that climate change between 2031 and 2060 is anticipated to cause a significant decrease in wheat yield and an increase in wheat protein concentration compared to the period from 1981 to 2010. Albumin and globulin are projected to decrease, while gliadin and glutenin are expected to increase, respectively. The average glutenin-to-gliadin ratio in the baseline is 1.096, whereas in scenarios SSP2–4.5 and SSP5–8.5, it is 1.093 and 1.102, respectively. Adapted measures can effectively synergize to enhance both wheat protein quality and yield under climate change. Specifically, delaying sowing and reducing nitrogen application to 210–240 kg·ha−1 with 200–240 mm of irrigation contribute to maintaining yields at the current conventional treatment level. Furthermore, these practices result in a 3.89 % and 0.13 % increase in grain protein concentration, and a 1.19 % and 6.02 % enhancement in the glutenin-to-gliadin ratio under scenarios SSP2–4.5 and SSP5–8.5, respectively, compared to conventional treatments. This comprehensive analysis provides valuable insights into practical strategies for synergistically improving wheat yield and protein quality in the face of climate change.

Recent discoveries in mRNA modification have highlighted N1-methyladenosine (m1A), but its role in preeclampsia (PE) pathogenesis remains unclear. In this study, we utilized methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) to identify m1A peaks and the expression profile of mRNA in the decidua of humans with early-onset PE (EPE), late-onset PE (LPE), and normal pregnancy (NP). We assessed the m1A modification patterns in preeclamptic decidua using 10 m1A modulators. Our bioinformatic analysis focused on differentially methylated mRNAs (DMGs) and differentially expressed mRNAs (DEGs) in pairwise comparisons of EPE vs. NP, LPE vs. NP, and EPE vs. LPE, as well as m1A-related DEGs. The comparisons of EPE vs. NP, LPE vs. NP, and EPE vs. LPE identified 3110, 2801, and 2818 DMGs, respectively. We discerned three different m1A modification patterns from this data. Further analysis revealed that key PE-related DMGs and m1A-related DEGs predominantly influence signaling pathways critical for decidualization, including cAMP, MAPK, PI3K-Akt, Notch, and TGF-β pathways. Additionally, these modifications impact pathways related to vascular smooth muscle contraction, estrogen signaling, and relaxin signaling, contributing to vascular dysfunction. Our findings demonstrate that preeclamptic decidua exhibits unique mRNA m1A modification patterns and gene expression profiles that significantly alter signaling pathways essential for both decidualization and vascular dysfunction. These differences in m1A modification patterns provide valuable insights into the molecular mechanisms influencing the decidualization process and vascular function in the pathogenesis of PE. These m1A modification regulators could potentially serve as potent biomarkers or therapeutic targets for PE, warranting further investigation.

Background: Bevacizumab (BV) is widely used in routine cancer treatment and clinical therapy in combination with many other agents. This study aims to describe and analyse post-market cases of pulmonary haemorrhage and haemoptysis reported with different BV treatment regimens by mining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.Methods: Data were collected from the FAERS database between 2004 Q1 and 2023 Q1. Disproportionality analysis including the reporting odds ratio (ROR) was employed to quantify the signals of disproportionate reporting of pulmonary haemorrhage and haemoptysis adverse events (AEs) associated with BV-related treatment regimens. The demographic characteristics, time to onset and outcomes were further clarified.Results: A total of 55,184 BV-associated reports were extracted from the FAERS database, of which 497 reports related to pulmonary haemorrhage and haemoptysis. Overall, the median onset time of pulmonary haemorrhage and haemoptysis AEs was 43 days (interquartile range (IQR) 15-117 days). In the subgroup analysis, BV plus targeted therapy had the longest median onset time of 90.5 days (IQR 34-178.5 days), while BV plus chemotherapy had the shortest of 40.5 days (IQR 14–90.25). BV plus chemotherapy disproportionately reported the highest percentage of death (148 deaths out of 292 cases, 50.68%). Moreover, the BV-related treatments including four subgroups in our study demonstrated the positive signals with the association of disproportionate reporting of pulmonary haemorrhage and haemoptysis. Notably, BV plus chemotherapy showed a significant higher reporting risk in pulmonary haemorrhage and haemoptysis signals of disproportionate reporting in comparison to BV monotherapy (ROR 5.35 [95% CI, 4.78–6.02] vs. ROR 4.19 [95% CI, 3.56–4.91], p = 0.0147).Conclusion: This study characterized the reporting of pulmonary haemorrhage and haemoptysis, along with the time to onset and demographic characteristics among different BV-related treatment options. It could provide valuable evidence for further studies and clinical practice of BV.

Chinese mitten crab, Eriocheir sinensis, is a migratory crustacean that grows in freshwater and reproduces in seawater. As a traditional aquatic product treasure in China, the industry of E. sinensis has become one of the unique freshwater fishery pillar industries. With years of development, a relatively complete industrial chain model has been initially formed, and its culture area, output and trade are constantly growing. However, the lag of aquatic product processing industry limits the large-scale development of the E. sinensis industry chain. In order to further explore the industry advantages and scale, it is urgent to vigorously develop the E. sinensis processing industry and promote the industrial optimization and upgrading. Moreover, strengthen scientific and technological support and reduce market risks by means of technological innovation to promote the healthy development of the industrial chain. This review expounds the current situation and existing problems of crab product processing in China, and the prospects of future product processing and sustainable utilization, in order to provide new insights for the large-scale development of E. sinensis industry chain.

Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, have become a standard treatment for multiple cancer types. However, ICIs can induce immune-related adverse events, with hepatitis-related adverse events (HRAEs) being of particular concern. Our objective is to identify and characterize HRAEs that exhibit a significant association with ICIs using real-world data.Methods: In this observational and retrospective pharmacovigilance study, we extracted real-world adverse events reports from the FDA Adverse Event Reporting System database spanning from the first quarter of 2004 to the first quarter of 2023. We conducted both Frequentist and Bayesian methodologies in the framework of disproportionality analysis, which included the reporting odds ratios (ROR) and information components (IC) to explore the intricate relationship between ICIs and HRAEs.Results: Through disproportionality analysis, we identified three categories of HRAEs as being significantly related with ICIs, including autoimmune hepatitis (634 cases, ROR 19.34 [95% CI 17.80–21.02]; IC025 2.43), immune-mediated hepatitis (546 cases, ROR 217.24 [189.95–248.45]; IC025 4.75), and hepatitis fulminant (80 cases, ROR 4.56 [3.65–5.70]; IC025 0.49). The median age of patients who report ICI-related HRAEs was 63 years (interquartile range [IQR] 53.8–72), with a fatal outcome observed in 24.9% (313/1,260) of these reports. Cases pertaining to skin cancer, lung cancer, and kidney cancer constituted the majority of these occurrences. Patients treated with anti-PD-1 or anti-PD-L1 antibodies exhibited a higher frequency of immune-mediated hepatitis in comparison to those undergoing anti-CTLA-4 monotherapy, with a ROR of 3.59 (95% CI 1.78–6.18). Moreover, the dual ICI therapy demonstrated higher reporting rates of ICI-related HRAEs compared to ICI monotherapy.Conclusion: Our findings confirm that ICI treatment carries a significant risk of severe HRAEs, in particular autoimmune hepatitis, immune-mediated hepatitis, and hepatitis fulminant. Healthcare providers should exercise heightened vigilance regarding these risks when managing patients receiving ICIs.

BackgroundST-segment elevation myocardial infarction (STEMI) persists to be prevalent in the elderly with a dismal prognosis. The capacity of endothelial progenitor cells (EPCs) is reduced with aging. Nevertheless, the influence of aging on the functionality of EPCs in STEMI is not fully understood.MethodThis study enrolled 20 younger STEMI patients and 21 older STEMI patients. We assessed the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events Risk (GRACE) scores in two groups. Then, we detected EPC migration, proliferation, adhesion, and plasma interleukin (IL)-18 and IL-23 concentrations in two groups. In addition, we analyzed the interconnection between age, EPC function, plasma IL-18 and IL-23 concentrations, and GRACE or TIMI scores in STEMI patients.ResultGRACE and TIMI scores in older STEMI patients were higher than in younger STEMI patients, whereas EPC function declined. GRACE and TIMI scores were found to have an inverse relationship with the EPC function. In older STEMI patients, plasma concentrations of IL-18 and IL-23 increased. Plasma IL-18 and IL-23 concentrations were adversely connected to EPC capacity and positively related to GRACE and TIMI scores. Moreover, age was positively correlated with plasma IL-18 or IL-23 concentrations, as well as GRACE or TIMI scores. However, age was adversely correlated with EPC function.ConclusionIn patients with STEMI, aging results in declined EPC function, which may be associated with inflammatory cytokines. The current investigation may offer new perception about mechanism and therapeutic targets of aging STEMI.

Memory is closely associated with neuronal activity and dendritic spine formation. Low-intensity transcranial ultrasound stimulation (TUS) improves the memory of individuals with vascular dementia (VD). However, it is unclear whether neuronal activity and dendritic spine formation under ultrasound stimulation are involved in memory improvement in VD. In this study, we found that seven days of TUS improved memory in VD model while simultaneously increasing pyramidal neuron activity, promoting dendritic spine formation, and reducing dendritic spine elimination. These effects lasted for 7 days but disappeared on 14 d after TUS. Neuronal activity and dendritic spine formation strongly corresponded to improvements in memory behavior over time. In addition, we also found that the memory, neuronal activity and dendritic spine of VD mice cannot be restored again by TUS of 7 days after 28 d. Collectively, these findings suggest that TUS increases neuronal activity and promotes dendritic spine formation and is thus important for improving memory in patients with VD.

In the field of abstract text summarization, architectures based on encoder-decoder frameworks are widely applied to sequence-to-sequence generation tasks and can effectively handle sequences of unlimited length. Subsequently, the transformer model use a global attention mechanism, allowing encodings at different distances to mutually interact, greatly enhancing the model’s contextual awareness. However, this context-awareness is global, requiring the model to additionally learn to extract different levels of information to increase understanding. We improve the structure of the model to introduce prior knowledge so that it can learn from the global and local information and enhance the model’s understanding ability. This paper proposes global information-aware encoding and local information-aware encoding, which enhance the understanding of documents from coarse-grained and fine-grained perspectives respectively. Global encoding adds an extra feature to the encoder stage and performs attention with the document, generating a global summary encoding of the entire document to guide the generation of the summary content. Local encoding is to perform local convolution on the features extracted by the encoder, use prior knowledge to extract local features of the document and enable the model to quickly extract local detail information. Experiments show that the improved model proposed in this paper has higher rouge scores than the baseline model on the LCSTS and CSL datasets, and also has advantages over some mainstream models. The generated summaries are more accurate and informative. The code is available on github. url: https://github.com/keptupp/A-text-summarization-approach-to-enhance-global-and-local-information-awareness-of-transformer.

Abstract There is a growing body of evidence indicating a close association between inflammatory bowel disease (IBD) and disrupted intestinal homeostasis. Excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with an increase in M1 proinflammatory macrophage infiltration during the activation of intestinal inflammation, plays a pivotal role in disrupting intestinal homeostasis in IBD. The overabundance of ROS/RNS can cause intestinal tissue damage and the disruption of crucial gut proteins, which ultimately compromises the integrity of the intestinal barrier. The proliferation of M1 macrophages contributes to an exaggerated immune response, further compromising the intestinal immune barrier. Currently, intestinal nanomaterials have gained widespread attention in the context of IBD due to their notable characteristics, including the ability to specifically target regions of interest, clear excess ROS/RNS, and mimic biological enzymes. In this review, we initially elucidated the gut microenvironment in IBD. Subsequently, we delineate therapeutic strategies involving two distinct types of nanomedicine, namely inorganic nanoparticles and natural product nanomaterials. Finally, we present a comprehensive overview of the promising prospects associated with the application of nanomedicine in future clinical settings for the treatment of IBD (graphic abstract). Graphical Abstract Different classes of nanomedicine are used to treat IBD. This review primarily elucidates the current etiology of inflammatory bowel disease and explores two prominent nanomaterial-based therapeutic approaches. First, it aims to eliminate excessive reactive oxygen species and reactive nitrogen species. Second, they focus on modulating the polarization of inflammatory macrophages and reducing the proportion of pro-inflammatory macrophages. Additionally, this article delves into the treatment of inflammatory bowel disease using inorganic metal nanomaterials and natural product nanomaterials

The color and texture of camouflaged objects closely resemble their backgrounds, making it difficult to distinguish between the target and the background. Additionally, camouflaged environments are complex, with some camouflaged objects overlapping significantly with the background, further complicating the identification of camouflaged target areas. To address these challenges, we present a novel double-branch camouflaged object detection algorithm, termed TDNet, inspired by biological vision and based on the classical convolutional neural network ResNet50. TDNet employs a two-stage target detection structure that utilizes location segmentation to accurately identify detection targets. Specifically, we introduce an internal feature interaction mechanism (IFE) that enhances camouflaged target feature representations through multi-dimensional spatial feature enhancement and multi-channel feature interaction, enabling the rough segmentation of camouflaged regions. To mitigate the issue of blurred boundaries of camouflaged targets, we devise a cross-layer feature fusion mechanism (CFU) to refine the borders of camouflaged regions. Moreover, we employ a multi-supervised approach to constrain the model’s degradation process, ensuring the accuracy of camouflaged object detection. Experimental results demonstrate that our proposed method outperforms nine classical camouflaged object detection algorithms, achieving state-of-the-art performance. We will release the code and the test maps at https://github.com/zc199823/TDNet.

In the marine field, infrared detection technology is of great significance for timely localization and detection of ships in security missions. However, since infrared ship targets are often in the environmental conditions of small pixel occupancy, low contrast and complex background, it poses a great challenge for multiship detection, classification, and localization tasks. Therefore, to address these problems we propose an edge information-guided infrared ship target detection (EGISD-YOLO) network, in which a dense-csp structure is designed to improve the csp module of YOLO to increase the reusability of the backbone feature information, and in addition, to address the noise and interference generated by the image in the complex background, a deconvolutional channel attention module (DCA) is designed to link the contextual language to the image, which relates the contextual semantics to obtain the local information of the target. Crucially, we propose an edge-guided structure that takes the edge information of low-level features as a cue to fuse with deep-level features to enrich the target contour and thus improve the target localization ability, so that the network still possesses robustness under low-contrast conditions, and finally, we add a small-size prediction head at the end of the network to further increase the detection ability of weak targets. The proposed EGISD-YOLO is experimentally demonstrated to have better detection performance for infrared ship targets.

In recent years, jute, as an important natural fiber crop, has become more and more significant in the production process of insect pests, causing serious harm to agricultural production. Especially in the field of crop pest identification with complex backgrounds, fuzzy features, and multiple small targets, the lack of datasets specifically for jute pests has led to the large limitations of traditional pest identification models in terms of generalization. At the same time, the research on models specifically for jute pest detection is still in its infancy. To solve this problem, we constructed a large-scale image dataset containing nine types of jute pests, which was highly targeted and could effectively support model training and evaluation. In this study, we developed a deep convolutional neural network model based on YOLOv7, namely JutePest-YOLO. The model has optimized the Backbone, Head, and loss functions of the baseline model, and introduced the new ELAN-P module and P6 detection layer, which effectively improved the model’s ability to identify jute pests in complex backgrounds. The experimental results showed that compared with the baseline model, the Precision, Recall, and F1 scores of the JutePest-YOLO model were improved by 3.45%, 1.76%, and 2.58%, respectively; the mAP@0.5 and mAP@0.5:0.95 was improved by 2.24% and 3.25%, and the overall model’s computation (GFLOPS) was reduced by 16.05%. Compared to other advanced methods such as YOLOv8s, JutePest-YOLO has achieved superior performance in terms of detection accuracy, with a precision of 98.7% and mAP@0.5 reaching 95.68%. As a result, JutePest-YOLO not only achieved significant improvement in recognition accuracy but also optimized computational efficiency. It’s a high-performance, lightweight solution for jute pest detection.

Realizing a spatial phase modulation (SPM) from 0 to 2π is vital for achieving precise light field manipulation, when the phase-only spatial light modulator (SLM) is driven by the voltage. However, insufficient bias voltage degrades the quality of the generated structured light. Here, we propose a superpixel method that consists of 2 × 2 adjacent pixels to equalize the imperfect SPM response, when the bias voltage is insufficient. Meanwhile, a look-up table (LUT) is established between the target light field and the superpixel equalized light field, for reducing the computational complexity of phase hologram generation. When the phase modulation depth is reduced from 2π to 1.67π, we can generate the vortex beams with better quality by the superpixel technique. Characterizing the spatial phase distribution of vortex beams through interferometry verifies the correct function of the superpixel enabled SPM equalization method. In addition, the peak signal-to-noise ratio (PSNR) is used as the metric to quantitatively evaluate the quality of the generated vortex beam. Compared with the phase modulation distortion caused by the insufficient bias voltage, the PSNR after the superpixel enabled SPM equalization is improved by 4.5 dB. Our results would facilitate various applications mediated by power-efficient phase modulation utilizing the SLM.