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In this contribution, the complicated dynamical behaviors and optimal harvesting policy of a discrete-time predator–prey model with fear and refuge effects are formulated. Both the fear and prey refuge effects refer to an interaction between predator and prey. In the first place, the existence and local stability of three fixed points of proposed model are investigated by virtue of our methodology, that is, the eigenvalues of the Jacobian matrix. One step further, it is worth mentioning that the model undergoes flip bifurcation (i.e., period–doubling bifurcation) and Neimark–Sacker bifurcation at the interior fixed point by the utilization of bifurcation theory and center manifold theory. Also, optimal harvesting strategy is investigated, and the expressions of optimal harvesting efforts are determined. Two examples, in the end, are put forward to prove that they are consistent with the previous theoretical results.

In recent years, the incidence of cosmetic injection-induced botulism has remarkably increased due to the frequent usage of botulinum neurotoxin type A (BoNT/A). To mimic and investigate this new clinical type of botulism, we established a novel animal model and evaluated the therapeutic potential of a new drug. Firstly, we injected BoNT/A into the gastrocnemius of rats to induce partial paralysis of the remaining limbs. Then, the intoxicated rats were treated with 3,4-diaminopyridine (3,4-DAP) at different stages of the disease and the forelimbs grasping strength (FGS) was evaluated. We showed that, at the sublethal dose, the FGS began to decrease at 6.00 ​± ​1.86 ​h after injection in rats, from 2.28 ​± ​0.19 ​N to 1.51 ​± ​0.18 ​N, while the FGS declined appeared earlier (4.29 ​± ​0.42 ​h) at the lethal dose, from 2.30 ​± ​0.20 ​N to 1.20 ​± ​0.16 ​N. Treatment with 3,4-DAP respectively at the time of the symptoms onset or 7 days after injection both can temporarily reverse the symptoms of muscle paralysis, indicating that 3,4-DAP may be an effective approach to relieve botulism. Overall, this study provides an available rat model and a promising therapeutic strategy for cosmetic injection-induced botulism.

Abstract From a meaning-oriented perspective, the study drew on the nominalization in Systemic Functional Linguistics with Coh-Metrix and interviews to check how L2 academic writing of student writers may develop with the implementation of task-type repetition (TtR). The findings revealed that the development of L2 academic writing was presumably staged rather than constantly linear. Over the development, language proficiency dynamically resonated with TtR. First, the beginning session of TtR (from Task 1 to around Task 4) witnessed a more dynamic developmental trajectory during which the low-proficiency student constantly outperformed the other two in inter-sentential cohesion, while the intermediate-level student stood out over the middle session (Task 4- around Task 8). Second, at three genre stagings, students’ genre knowledge deeply resonated with their meaning-making activities throughout TtR, particularly in facilitating individual iterative reflection on their established writing knowledge. Third, the deficiency of genre knowledge may cause wide-range absence of nominalization at DESCRIPTION and CONCLUSION than EXPOSITION. Fourth, the linguistic fossilization identified at DESCRIPTION implies that anaphoric reconstrual may be individually mediated (by grammatically complicating the syntax in the study). Finally, a nuanced improvement in metaphorical enrichment and control was identified.

Abstract Background Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with the tumor microenvironment (TME) playing a crucial role in its progression. Aggregated autophagy (AA) has been recognized as a factor that exacerbates CRC progression. This study aims to study the relationship between aggregated autophagy and CRC using single-cell sequencing techniques. Our goal is to explain the heterogeneity of the TME and to explore the potential for targeted personalized therapies. Objective To study the role of AA in CRC, we employed single-cell sequencing to discern distinct subpopulations within the TME. These subpopulations were characterized by their autophagy levels and further analyzed to identify specific biological processes and marker genes. Results Our study revealed significant correlations between immune factors and both clinical and biological characteristics of the tumor microenvironment (TME), particularly in cells expressing TUBA1B and HSP90AA1. These immune factors were associated with T cell depletion, a reduction in protective factors, diminished efficacy of immune checkpoint blockade (ICB), and enhanced migration of cancer-associated fibroblasts (CAFs), resulting in pronounced inflammation. In vitro experiments showd that silencing TUBA1B and HSP90AA1 using siRNA (Si-TUBA1B and Si-HSP90AA1) significantly reduced the expression of IL-6, IL-7, CXCL1, and CXCL2 and inhibition of tumor cell growth in Caco-2 and Colo-205 cell lines. This reduction led to a substantial alleviation of chronic inflammation and highlighted the heterogeneous nature of the TME. Conclusion This study marks an initial foray into understanding how AA-associated processes may potentiate the TME and weaken immune function. Our findings provide insights into the complex dynamics of the TME and highlight potential targets for therapeutic intervention, suggesting a key role for AA in the advancement of colorectal cancer.

This paper investigated the influence of ultraviolet (UV) illumination on the corrosion behavior of 7A04 aluminum alloy in 3.5% NaCl solutions with various pH values (pH=5.0, 7.0, and 10.0) using weight loss measurement, electrochemical methods, and surface analysis techniques. The research results indicated that the corrosion products of 7A04 alloy in salt solutions with different pH values all exhibited n-type semiconductor properties and could trigger the photovoltaic effect under UV illumination. Simultaneously, UV illumination reduced the compactness of the corrosion products, inhibited the enrichment of copper compounds (Cu2O), and promoted the generation of hydroxyl radicals in the solution. Therefore, UV illumination significantly accelerated the corrosion process of 7A04 alloy, with the overall acceleration effect ranking as follows: alkaline > neutral > acidic. In addition, the corrosion mechanism of 7A04 alloy in the test solutions with and without UV illumination was also discussed in this paper.

Abstract Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a protein that regulates apoptosis and programmed cell death. This research aims to evaluate its potential role in inhibiting breast cancer cell proliferation, migration, and glycolysis and uncover its underlying molecular mechanism. We collected breast cancer tissue samples from eight patients between January 2019 and June 2023 in our Hospital to analyse CIAPIN1 expression. We transfected human breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-453, and MDA-MB-468) with siRNA of CIAPIN1. Finally, we determined protein expression using RT-qPCR and Western blotting. CIAPIN1 expression was elevated in both breast cancer tissue and serum. Overexpression of CIAPIN1 detected in the breast cancer cell lines MCF7 and MDA-MB-468. In addition, CIAPIN1 overexpression increased cell proliferation and migration rate. CIAPIN1 downregulation suppressed cell proliferation while elevated cellular apoptosis, reactive oxygen species (ROS) production and oxidative stress in breast cancer cells. Moreover, CIAPIN1 inhibition remarkably suppressed pyruvate, lactate and adenosine triphosphate (ATP) production and reduced the pyruvate kinase M2 (PKM2) protein expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) in breast cancer cells. Downregulation of CIAPIN1 suppresses cell proliferation, migration and glycolysis capacity in breast cancer cells by inhibiting the STAT3/PKM2 pathway.

Four new species of Yunguirius B. Li, Zhao & S.Q. Li, 2023 are described from China, namely: Yunguirius parvus Wei & Liu, sp. nov. (♀), Yunguirius trigonus Wei & Liu, sp. nov. (♀), Yunguirius wangqiqiae Wei & Liu, sp. nov. (♀), and Yunguirius xiannushanensis Wei & Liu, sp. nov. (♀).

The common walnut (Juglans regia) is one of the most economically important nut trees cultivated worldwide. Despite its importance, no comprehensive evaluation of walnut tree population genetics has been undertaken across the range where it originated, Central Asia. In this study, we investigated the genetic diversity and population structure of 1082 individuals from 46 populations across Central Asia. We found moderate genetic diversity of J. regia across Central Asia, with 46 populations clustered into three groups with a weak relationship between genetic and geographic distance. Our findings reveal that the western Himalaya might be the core region of common walnut genetic diversity in Central Asia and that, except for two populations in Gongliu Wild Walnut Valley, humans might have introduced walnut populations to Xinjiang, China. The observed distribution of the genetic landscape has probably been affected by historical climate fluctuation, breeding system, and prolonged anthropogenic activity. We propose the conservation of the core genetic diversity resources in the western Himalaya and pay special attention to populations from Gongliu in Xinjiang. These findings enhance our understanding of the genetic variation throughout the distribution range of J. regia in Central Asia, which will provide a key prerequisite for evidence-based conservation and management.

To reduce the losses caused by aging failure of insulation gate bipolar transistor (IGBT), which is the core components of nuclear power plant rod position indicating and rod control (RPC) system. It is necessary to conduct studies on its life prediction. The selection of IGBT failure characteristic parameters in existing research relies heavily on failure principles and expert experience. Moreover, the analysis and learning of time-domain degradation data have not been fully conducted, resulting in low prediction efficiency as the monotonicity, time correlation, and poor anti-interference ability of extracted degradation features. This paper utilizes the advantages of the stacked denoising autoencoder(SDAE) network in adaptive feature extraction and denoising capabilities to perform adaptive feature extraction on IGBT time-domain degradation data; establishes a long-short-term memory (LSTM) prediction model, and optimizes the learning rate, number of nodes in the hidden layer, and number of hidden layers using the Gray Wolf Optimization (GWO) algorithm; conducts verification experiments on the IGBT accelerated aging dataset provided by NASA PCoE Research Center, and selects performance evaluation indicators to compare and analyze the prediction results of the SDAE-LSTM model, PSO-LSTM model, and BP model. The results show that the SDAE-LSTM model can achieve more accurate and stable IGBT life prediction.

ABSTRACT: Salmonella is a major cause of foodborne diseases worldwide. Conventional rapid assays for detecting Salmonella in real samples often encounter severe matrix interference or detect a limited number of species of a genus, resulting in inaccurate detection. In this study, we developed a method that combined phage-based magnetic capture with real-time recombinase polymerase amplification (RPA) for the rapid, highly sensitive, and specific detection of Salmonella in milk with an ultra-low detection limit. The Felix O-1 phage-conjugated magnetic beads (O-1 pMBs) synthesized in this method showed excellent capture ability for Salmonella spp. and ideal specificity for non-Salmonella strains. After O-1 pMBs-based magnetic separation, the limit of detection of the real-time RPA assay was 50 cfu/mL in milk samples, which was significantly increased by a magnitude of 3 to 4 orders. The method exhibited a high sensitivity (compatibility) of 100% (14/14) for all tested Salmonella serotype strains and an ideal specificity (exclusivity) of 100% (7/7) for the tested non-Salmonella strains. The entire detection process, including Salmonella capture, DNA extraction, and real-time RPA detection, was completed within 1.5 h. Furthermore, milk samples spiked with 10 cfu/25 mL of Salmonella were detected positive after being cultured in buffered peptone water for only 3 h. Therefore, the proposed method could be an alternative for the rapid and accurate detection of Salmonella.

Two large-scale snow and rain weather processes occurred in china from February 1-4, 2024 (Process 1, hereinafter), and February 19-24, 2024 (Process 2, hereinafter). During these two weather processes, the impact of freezing rain was extensive, the intensity of the disaster was severe, and the duration was long, which was rare in history. This study utilized multi-source observational data and ERA5 reanalysis data to focus on analyzing the environmental conditions and temperature layer characteristics of these two freezing rain events. The results indicate: (1) During both weather events, the 500 hPa weather patterns and influencing systems were quite similar, which were stably sustained, providing favorable conditions for widespread snow, rain, and freezing weather. However, there were differences in the low-level temperature configuration and the speed of movement. In Process 1, due to the slower movement of the cold air, the distribution of freezing rain was more concentrated. The initial southwest jet stream in Process 2 was stronger and positioned further north compared to Process 1, leading to the occurrence of freezing rain further northward. However, in the later stages, the rapid southward movement of strong cold air caused a fast-moving rain, snow, and ice, and thus a larger impacting range of the freezing rain. (2) In both processes, the mid-level warm layer was mainly located between 700 hPa and 850 hPa, while the low-level cold layer was mainly located below 900 hPa. The positions were lower than the classic conceptual model of a warm layer at 700 hPa and a cold layer at 850 hPa, which could easily lead to misjudgment of the weather situations and types. (3) Using the area method, the strength of the mid-level warm layer and the low-level cold layer was calculated separately for both processes. The results show that the strength of the warm and cold layers in Process 1 was weaker than in Process 2. In addition, the freezing rain in both processes mainly occurred in areas where the strength of the mid-level warm layer and the low-level cold layer were close.

In ecology, the most significant aspect is that the interactions between predators and prey are extremely complicated. Numerous experiments have shown that both direct predation and the fear induced in prey by the presence of predators lead to a reduction in prey density in predator-prey interactions. In addition, a suitable shelter can effectively stop predators from attacking as well as support the persistence of prey population. There has been less exploration of the effects of not only fear but also refuge factors on the dynamics of predator prey interactions. In this paper, we unveil several conclusions about a predator-prey system with fuzzy parameters, considering the cost of fear in two prey species and the effect of shelter on two prey species and one predator. As the first step of the investigation, the boundedness and non-negativity of the solutions to the system are put forward. Using the Jocabian matrix and Lyapunov function methods, we further analyze the existence and stability of the available equilibria and also the existence of Hopf bifurcation, considering the fear parameter as the bifurcation parameter that has been observed by applying the normal form theory. Finally, numerical simulations help us better understand the dynamics of the model, in which some interesting chaotic phenomena are also exhibited.

Abstract Background Cancer cells can resist chemotherapy through various mechanisms, diminishing treatment outcomes. Research had indicated that combining miR-122 with doxorubicin (DOX) can improve hepatocellular carcinoma (HCC) therapy. Results To explore this, we created a one-pot co-delivery system, Fe-miR-122/DOX, by coordinating miR-122, DOX, and FeII ions into nanoparticles. These nanoparticles display uniform particle sizes, well-defined morphology, and exceptional colloidal stability in 10% FBS and 20% FBS solution over 24 h. When the ratio of DOX to miR-122 was set at 20:1, the loading efficiency of both drugs reached 54.7% and 55.5%, respectively. Cell experiments confirmed that Fe-miR-122/DOX efficiently delivers both miR-122 and DOX, enabling cytoplasmic delivery through lysosomal escape, facilitated by the positive charge of the nanoparticles. Functionally, miR-122 increases intracellular accumulation of DOX by downregulating P-glycoprotein (P-gp) expression, and it promotes apoptosis by downregulating B-cell lymphoma 2 (Bcl-2), which leads to the upregulation of Caspase-3. Additionally, Fe-miR-122/DOX disrupts cIAPs-mediated anti-apoptotic signals, downregulates PARP-1 expression, hinders DNA repair, promotes DNA fragmentation, enhances caspase-3 expression, and triggers programmed cell death, synergistically enhancing its antitumor efficacy. This synergistic mechanism disrupts DNA repair, amplifying DNA damage and apoptosis. Our cytotoxicity and apoptosis assays (with a HepG2 cell apoptosis rate of 85.98%) demonstrated the potent antitumor capability of Fe-miR-122/DOX. Conclusions This innovative system has demonstrated good biocompatibility and has the potential to transform HCC therapy. Future research could focus on optimizing the co-delivery system and assessing its efficacy in clinical trials.

Abstract A significant number of steep cracks are frequently encountered in underground engineering, posing a threat to operation. The high-pressure grouting method is a commonly utilized repair technique. Nevertheless, conventional grout is prone to displacement due to its weight, making it challenging to ensure adequate filling of the cracks. Therefore, this study aims to develop a grouting material with targeted displacement and anchoring properties. Firstly, an optimal magnetic slurry composition was determined through an orthogonal test. Subsequently, XRD and SEM were used to analyze the impact of the magnetic field on the composition distribution, internal pore structure, and transient viscosity of the slurry. Afterwards, a model for localized grout diffusion under magnetic was established. The results show that the application of a magnetic field caused the slurry to compact due to magnetic forces, reducing its porosity. Moreover, the dynamic viscosity of the slurry increased exponentially with rising magnetic induction intensity. Notably, a 40.5% increase in the diffusion area was observed when the magnetic field intensity rose from 2500 to 4500 GS. The error between the measured and theoretical values of the magnetic slurry diffusion model was only 8.91%, indicating the model's accuracy in describing the slurry diffusion process under magnetic field influence.

Abstract Aims To explore rare and difficult cases of undifferentiated embryonal sarcoma of the liver (UESL) in children in a single centre, summarize the diagnosis and treatment experience and analyse the role of a computer-assisted surgery system (Hisense CAS), thus providing a new global vision and three-dimensional perspective. Methods We retrospectively collected the clinical data including the diagnoses and treatment processes, of children with UESL confirmed by histopathological examination in our hospital from January 2009 to December 2020. The relationship between the tumour volume and important blood vessels and between the liver volume and tumour volume, as well as other three-dimensional characteristics in the reconstructed three-dimensional model were analysed using Hisense CAS. The findings from this analysis can be used to aid in surgical decision-making and preoperative planning. Results Four children—3 girls and 1 boy—with UESL were included in the study. The age at onset ranged from 6 to 8 years. All four children presented with symptoms of abdominal discomfort, and abdominal masses were detected during physical examination. Owing to the wishes of their parents and the possibility that the disease was benign, all four children underwent one-stage radical surgery. For patient 1, a three-dimensional reconstruction was created during the initial diagnosis, which made accurate evaluation and planning of the preoperative procedure challenging. In patient 2, the tumour was located in the middle lobe of the liver and involved the first and second hepatic hilum. For patient 3, the pathological diagnosis of the tumour after surgery was challenging, but eventually, the diagnosis was confirmed through histochemistry and consultation with higher-level hospitals. Patient 4 had a giant tumour, which had a preoperative simulated future liver remnant volume (FLV) that was 21.0% of the total volume of the liver and tumour (TLTV). According to the standard liver volume (SLV) for children, the FLV was 77.0% of the SLV, making surgery feasible. All four children underwent complete resection, and only patient 4 experienced recurrence below the diaphragm 19 months after surgery. Currently, the 3-year overall survival rate is 100%, and the 3-year event-free survival rate is 75%. Conclusion UESL in children is rare, and the key to diagnosis and treatment is complete surgical resection. Through individualized three-dimensional surgical planning, accurate and complete resection of difficult and complex UESL in children can be achieved, leading to a favourable prognosis.

Abstract Background The development of acquired EGFR-TKI treatment resistance is still a major clinical challenge in the treatment of non-small cell lung cancer (NSCLC). This study aimed to investigate the role of HDAC1/FOXK1/miR-33a signaling in EGFR-TKI resistance. Methods The expression levels of miR‐33a, HDAC1, and FOXK1 were examined using quantitative polymerase chain reaction (PCR) and bioinformatics analysis. Cell proliferation, migration, and apoptosis were explored by cell number assay, Transwell, and flow cytometry assays, respectively. After overexpression or knockdown of HDAC1, miR-33a expression in the cells, cell functions were tested. Immunoprecipitation and correlation analyses were used to evaluate the interaction between HDAC1 and FOXK1 protein. The tumor-suppressive role of miR-33a was investigated by animal experiments. Results The suppression of miR-33a increased TKI resistance by affecting cell proliferation, migration, and apoptosis in gefitinib-resistant cells. HDAC1 is the key upstream molecule that inhibits miR-33 expression. HDAC1 upregulation increased gefitinib resistance by its binding to FOXK1 in cells to silence miR-33a expression. MiR-33a overexpression exerts tumor-suppressive effects by negatively regulating ABCB7 and p70S6K1 expression. Moreover, overexpression of miR-33a inhibited tumor growth in a xenograft nude mouse model. Conclusions HDAC1/FOXK1 upregulation and miR-33a silencing are new mechanisms of EGFR-TKI resistance in NSCLC.

Abstract In real-life complex traffic environments, vehicles are often occluded by extraneous background objects and other vehicles, leading to severe degradation of object detector performance. To address this issue, we propose a method named YOLO-OVD (YOLO for occluded vehicle detection) and a dataset for effectively handling vehicle occlusion in various scenarios. To highlight the model attention in unobstructed region of vehicles, we design a novel grouped orthogonal attention (GOA) module to achieve maximum information extraction between channels. We utilize grouping and channel shuffling to address the initialization and computational issues of original orthogonal filters, followed by spatial attention for enhancing spatial features in vehicle-visible regions. We introduce a CIoU-based repulsion term into the loss function to augment the network’s localization accuracy in scenarios involving densely packed vehicles. Moreover, we explore the effect of the knowledge-based Laplacian Pyramid on the OVD performance, which contributes to fast convergence in training and ensures more detailed and comprehensive feature retention. We conduct extensive experiments on the established occluded vehicle detection dataset, which demonstrates that the proposed YOLO-OVD model significantly outperforms 14 representative object detectors. Notably, it achieves improvements of 4.7% in Precision, 3.6% in AP@0.5, and 1.9% in AP@0.5:0.95 compared to the YOLOv5 baseline.

Abstract The marine ecological red lines (MERLs) is an institutional innovation of the Chinese government to seek a balance between ecological protection and social development. China’s MERLs was designated in 2017, but there are problems such as insufficient consideration of areas of high ecological importance and lack of convergence with marine functional zoning. This paper carries out the adjustment of the MERLs in China by constructing the methods of marine ecological importance assessment and human activities disposal assessment, and the results show that after the adjustment, the type and distribution pattern of China’s MERLs is more reasonable, the areas of high ecological importance in the MERLs increases significantly, the intensity of human activities in the MERLs declines significantly, and the unification with the use of marine space is realized. China’s adjustment of the MERLs is based on scientific assessment and realizes the coordination of development and protection, which can provide a reference for global marine ecological protection.

Abstract Constructing highways in deserts is expensive due to the difficulty of acquiring materials; utilizing aeolian sand effectively has become a problem, especially in the Xinjiang region, where the desert widely occurs. This paper aims to investigate the vibration response of a geocell-reinforced aeolian sand subgrade under traffic loading based on field tests of highways in deserts. The vibration acceleration response of geocell-reinforced aeolian sand and gravelly soil upper roadbed structures is tested. The field test results illustrate the effects of dynamic loading on geocell-reinforced aeolian sand roadbeds, and the thickness substitution ratio between geocell-reinforced aeolian sand roadbeds and conventional gravelly soil roadbeds is determined and verified based on the vibration acceleration monitoring values. The results show that the vibration response induced by the test vehicle is concentrated within the 30 Hz frequency band, and the higher the vibration frequency, the faster the vertical decay in the road. The vibration damping capacity of the reinforced aeolian sand roadbed is better than that of the gravelly soil roadbed; when replacing the gravelly soil roadbed with the reinforced aeolian sand roadbed, the substitution ratio is 0.31–0.42. It is verified that half thickness of gravel soil on roadbeds can be replaced by geocell-reinforced aeolian sand under different working conditions. The results of this study can provide reference data for the design of highway subgrades in deserts.

Abstract Among the many adverse geological disasters, the surge water disaster in karst areas causes the greatest loss to underground engineering construction, so it is necessary to carry out relevant research on the management of surge water disaster in karst pipelines. This study presents the creation of an oily epoxy resin magnetic convergence grouting material (OEMS) specifically developed to prevent water infiltration in pipelines. A self-designed visual karst pipeline grouting simulation system was used to conduct an experimental study on the diffusion and plugging behavior of magnetic slurry grouting. A model was constructed to simulate the migration of a magnetic slurry in water inrush circumstances. The model is based on the theory of slurry diffusion and the concept of magnetic adsorption. The results suggest that:(i) The best performance in grouting sealing is achieved when the ratio of new OEMS epoxy resin A liquid to B liquid is 2:1, and the blending ratio of flyash and Fe3O4 powder falls between 25 and 55%. (ii) The primary and secondary correlations among the parameters that affect the rate of change in flow rate, plugging pressure, and slurry retention rate are as follows: Hydrodynamic velocity has the greatest correlation, followed by plugging length, Fe3O4 power ratio, and flyash mixture ratio. (iii) The validity of the model is verified by comparing empirical observations with calculated theoretical values.

Abstract Photoacoustic tomography offers a powerful tool to visualize biologically relevant molecules and understand processes within living systems at high resolution in deep tissue, facilitated by the conversion of incident photons into low-scattering acoustic waves through non-radiative relaxation. Although current endogenous and exogenous photoacoustic contrast agents effectively enable molecular imaging within deep tissues, their broad absorption spectra in the visible to near-infrared (NIR) range limit photoacoustic multiplexed imaging. Here, we exploit the distinct ultrasharp NIR absorption peaks of lanthanides to engineer a series of NIR photoacoustic nanocrystals. This engineering involves precise host and dopant material composition, yielding nanocrystals with sharply peaked photoacoustic absorption spectra (~3.2 nm width) and a ~10-fold enhancement in NIR optical absorption for efficient deep tissue imaging. By combining photoacoustic tomography with these engineered nanocrystals, we demonstrate photoacoustic multiplexed differential imaging with substantially decreased background signals and enhanced precision and contrast.

Abstract Background Despite recent advances the prognosis of pulmonary hypertension remains poor and warrants novel therapeutic options. Extensive studies, including ours, have revealed that hypoxia-induced pulmonary hypertension is associated with high oxidative stress. Cerium oxide nanozyme or nanoparticles (CeNPs) have displayed catalytic activity mimicking both catalase and superoxide dismutase functions and have been widely used as an anti-oxidative stress approach. However, whether CeNPs can attenuate hypoxia-induced pulmonary vascular oxidative stress and pulmonary hypertension is unknown. Results In this study, we designed a new ceria nanozyme or nanoparticle (AuCeNPs) exhibiting enhanced enzyme activity. The AuCeNPs significantly blunted the increase of reactive oxygen species and intracellular calcium concentration while limiting proliferation of pulmonary artery smooth muscle cells and pulmonary vasoconstriction in a model of hypoxia-induced pulmonary hypertension. In addition, the inhalation of nebulized AuCeNPs, but not CeNPs, not only prevented but also blunted hypoxia-induced pulmonary hypertension in rats. The benefits of AuCeNPs were associated with limited increase of intracellular calcium concentration as well as enhancement of extracellular calcium-sensing receptor (CaSR) activity and expression in rat pulmonary artery smooth muscle cells. Nebulised AuCeNPs showed a favorable safety profile, systemic arterial pressure, liver and kidney function, plasma Ca2+ level, and blood biochemical parameters were not affected. Conclusion We conclude that AuCeNPs is an improved reactive oxygen species scavenger that effectively prevents and treats hypoxia-induced pulmonary hypertension. Graphical Abstract

Abstract Traditional optical anti-counterfeiting (AC) is achieved by static printed images, which makes them susceptible to lower levels of security and easier replication. Therefore, it is essential to develop AC device with dynamic modulation for higher security. Electrophoretic display (EPD) has the advantages of low power consumption, high ambient contrast ratio, and capability of showing dynamic images which is suitable for dynamic AC applications. Herein, we prepared a dynamical AC device based on a fluorescent EPD, and achieving the image switch between black, white, and green fluorescence states under the dual-mode driving (electronic field and UV light). We loaded perovskite quantum dots (CsPbBr3) onto the TiO2 particles and further prepared fluorescent electrophoretic particles TiO2/CsPbBr3-3-PLMA (TiO/CPB-3) by grafting and polymerizing method. In addition, we fabricated the AC devices based on the fluorescent EPD, which exhibits the multifunctional AC, where the fluorescent EPD has a fast response time of 350 ms, a high contrast ratio of 17, and bright green fluorescence. This prototype demonstrates a new way for future dynamic AC and identification.

The genus Xilithus Liu & Li, 2023 contains 22 species, three of which are known from Hubei Province, China: X. acerosus (Yao, Irfan & Peng, 2019), X. auritus (Fu, Zhang & Zhang, 2016) and X. xingdoushanensis (Yao, Irfan & Peng, 2019).One new Xilithus species from Hubei, China is described: X. qizimeishanensis Liu & Hu sp. nov. Morphological description, digital photos and distribution map are provided.

Abstract Background Rhododendron delavayi is a natural shrub that is distributed at different elevations in the karst region of Bijie, China, and that has an important role in preventing land degradation in this region. In this study, we determined the soil mineral element contents and soil enzyme activities. The composition of the soil bacterial community of R. delavayi at three elevations (1448 m, 1643 m, and 1821 m) was analyzed by high-throughput sequencing, and the interrelationships among the soil bacterial communities, mineral elements, and enzyme activities were determined. Results The Shannon index of the soil bacterial community increased and then decreased with increasing elevation and was highest at 1643 m. Elevations increased the number of total nodes and edges of the soil bacterial community network, and more positive correlations at 1821 m suggested stronger intraspecific cooperation. Acidobacteria, Actinobacteria and Proteobacteria were the dominant phyla at all three elevations. The Mantel test and correlation analysis showed that Fe and soil urease significantly affected bacterial communities at 1448 m; interestingly, Chloroflexi was positively related to soil urease at 1448 m, and Actinobacteria was positively correlated with Ni and Zn at 1821 m. Fe and soil urease significantly influenced the bacterial communities at lower elevations, and high elevation (1821 m) enhanced the positive interactions of the soil bacteria, which might be a strategy for R. delavayi to adapt to high elevation environments. Conclusion Elevation significantly influenced the composition of soil bacterial communities by affecting the content of soil mineral elements and soil enzyme activity.

Mountain excavation and city construction (MECC) projects being launched in the Loess Plateau in China involve the creation of large-scale artificial land. Understanding the subsurface evolution characteristics of the artificial land is essential, yet challenging. Here, we use an improved fiber-optic monitoring system for its subsurface multi-physical characterization. The system enables us to gather spatiotemporal distribution of various parameters, including strata deformation, temperature, and moisture. Yan'an New District was selected as a case study to conduct refined in-situ monitoring through a 77 m-deep borehole and a 30 m-long trench. Findings reveal that the ground settlement involves both the deformation of the filling loess and the underlying intact loess. Notably, the filling loess exhibits a stronger creep capability compared to underlying intact loess. The deformation along the profile is unevenly distributed, with a positive correlation with soil moisture. Water accumulation has been observed at the interface between the filling loess and the underlying intact loess, leading to a significant deformation. Moreover, the temperature and moisture in the filling loess have reached a new equilibrium state, with their depths influenced by atmospheric conditions measuring at 31 m and 26 m, respectively. The refined investigation allows us to identify critical layers that matter the sustainable development of newly created urban areas, and provide improved insights into the evolution mechanisms of land creation.

Abstract Background In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). Methods Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. Results Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). Conclusions Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications.

Abstract Background China braces for coronavirus disease 2019 (COVID-19) surge after adjusting the “zero COVID” strategy. We aimed to evaluate and compare the prevalence of clinical symptoms of the Omicron variant infection among people living with HIV (PLWH) and HIV-free people. Methods A cross-sectional study was conducted in Wuchang District, Wuhan, Hubei Province, in December 2022 by a self-administered online survey during the Omicron wave. Participants aged ≥ 18 years with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis were recruited. PLWH managed by the local healthcare system were recruited, while HIV-free people were recruited by sending out online surveys through WeChat. We compared the prevalence of clinical symptoms of COVID-19 between PLWH and HIV-free people, and factors associated with symptom occurrence among PLWH were accessed. Results Total, 687 PLWH and 1222 HIV-free people were enrolled. After adjusting sex, age, body mass index, comorbidities and COVID-19 vaccination status, the prevalences of all symptoms, including higher degree and long duration of fever (aOR 0.51, 95%CI 0·42 − 0·61; aOR 0.52, 95%CI 0·43 − 0·63), were significantly lower among PLWH than among HIV-free people. Among PLWH, CD4+ T lymphocyte count (CD4 count) between 350 ~ 499 cells/µL and detectable HIV viral load (HIV-VL) were associated with significantly decreased risks of fever (aOR 0·63, 95%CI 0·40 − 0·97; aOR 0·56, 95%CI 0·33 − 0·94), headache (aOR 0·61, 95%CI 0·41 − 0·91; aOR 0·55, 95%CI 0·34 − 0·92) and muscle soreness (aOR 0·57, 95%CI 0·39 − 0·84; aOR 0·57, 95%CI 0·39 − 0·84). No apparent association between the symptoms prevalence and three/four doses of inactivated COVID-19 vaccination among PLWH was observed; both males and older age were associated with significantly decreased risks of nasal congestion/runny nose (aOR 0·52, 95%CI 0·32 − 0·82; aOR 0·97, 95%CI 0·96 − 0·99) and headache (aOR 0·58, 95%CI 0·36 − 0·92; aOR 0·96, 95%CI 0·95 − 0·98); older age was associated with significantly decreased risks of higher degree of fever (aOR 0·97, 95%CI 0·95 − 0·98). Conclusions PLWH have significantly milder symptoms of the Omicron variant infection than HIV-free people. PLWH who are male, older, have low CD4 count, and detectable HIV-VL have reduced occurrence of COVID-19 symptoms. However, continuous monitoring should be conducted among PLWH during the COVID-19 pandemic.

Abstract The teaching objectives of traditional approaches in higher education emphasize mostly students’ mastery of knowledge and have insufficient directionality to social needs. In this study, we developed a BOPPPS (Bridge-in, Objectives, Pre-assessment, Participatory Learning, Post-assessment and Summary) teaching model combined with the OBE (Outcome Based Education) concept to enhance the teaching outcomes. Firstly, based on the graduation requirements and professional training objectives of students, we divided the course objectives into three dimensions (knowledge, ability and quality), and further specified into index points. Then, the teaching content of each chapter was set to correspond with the index points. Finally, the BOPPPS teaching model was used to meet each requirement. Clinical biochemistry testing course was used as a model to assess the effects of the teaching reform. After the class, the teaching effect was analyzed based on the questionnaire surveys from the students and their scores of both the chapter and final examinations. The results showed that compared with the traditional approach, the BOPPPS teaching model combined with the OBE concept has demonstrated a notable enhancement in student engagement, and significant improvement of their mastery of knowledge, application skills, and problem-solving abilities. The examination scores of the BOPPPS group were markedly higher than those of the traditional group. Moreover, the difference between the two groups diverse assessment scores was much bigger than that between the two group examination scores. Our study indicates that the BOPPPS teaching model combined with the OBE concept is a highly effective teaching model for enhancing the learning effectiveness of students.

Abstract Background Recent studies have shown that several long non-coding RNAs (lncRNAs) in the placenta are associated with preeclampsia (PE). However, the extent to which lncRNAs may contribute to the pathological progression of PE is unclear. Results Here, we report a hierarchical regulatory network involved in early-onset severe PE (EOSPE). We have carried out transcriptome sequencing on the placentae from patients and normal subjects to identify the differentially expressed genes (DEGs), including some lncRNAs (DElncRNAs). We then constructed a high-quality hierarchical regulatory network of lncRNAs, transcription factors (TFs), and target DEGs, containing 1851 lncRNA-TF interactions and 6901 TF-promoter interactions. The lncRNA-to-target regulatory interactions were further validated by the triplex structures between the DElncRNAs and the promoters of the target DEGs. The DElncRNAs in the regulatory network were clustered into 3 clusters, one containing DElncRNAs correlated with the blood pressure, including FLNB-AS1 with targeting 27.89% (869/3116) DEGs in EOSPE. We further demonstrated that FLNB-AS1 could bind the transcription factor JUNB to regulate a series members of the HIF-1 signaling pathway in trophoblast cells. Conclusions Our results suggest that the differential expression of lncRNAs may perturb the lncRNA-TF-DEG hierarchical regulatory network, leading to the dysregulation of many genes involved in EOSPE. Our study provides a new strategy and a valuable resource for studying the mechanism underlying gene dysregulation in EOSPE patients.

Abstract Prognostics and health management (PHM) has gotten considerable attention in the background of Industry 4.0. Battery PHM contributes to the reliable and safe operation of electric devices. Nevertheless, relevant reviews are still continuously updated over time. In this paper, we browsed extensive literature related to battery PHM from 2018 to 2023 and summarized advances in battery PHM field, including battery testing and public datasets, fault diagnosis and prediction methods, health status estimation and health management methods. The last topic includes state of health estimation methods, remaining useful life prediction methods and predictive maintenance methods. Each of these categories is introduced and discussed in details. Based on this survey, we accordingly discuss challenges left to battery PHM, and provide future research opportunities. This research systematically reviews recent research about battery PHM from the perspective of key PHM steps and provide some valuable prospects for researchers and practitioners.

Abstract Circulating cell-free DNA (cfDNA) in the peripheral blood is a promising biomarker for cancer diagnosis and prognosis. Somatic mutations identified in cancers have been used to detect therapeutic targets for clinical transformation and individualize drug selection, while germline variants can predict a patient’s risk of developing cancer and drug sensitivity. However, no platform has been developed to analyze, calculate, integrate, and friendly visualize these pan-cancer cfDNA mutations deeply. In this work, we performed panel sequencing encompassing 1,115 cancer-related genes across 16,659 cancer patients, spanning 27 cancer types. We detected 496 germline variants in leukocytes and 11,232 somatic mutations in the cfDNA of all patients. CPGV (Cancer Peripheral blood Gene Variations), a database constructed from this dataset, is the first pan-cancer cfDNA database that encompasses somatic mutations, germline variants, and further comparative analyses of mutations across different cancer types. It bears great promise to serve as a valuable resource for cancer research.

Abstract Electrification plays a crucial role in deep decarbonization. However, electrification and power infrastructure can cause mutual challenges. We use nationwide power outage and electric vehicle adoption data in China to provide empirical evidence on how power infrastructure failures can deter electrification. We find that when the number of power outages per district increases by 1 in a given month, the number of new electric vehicles adopted per month decreases by 0.99%. A doubling of power outages in one year on average across the nation can create a depressed adoption rate for up to a decade, implying a decline of more than $ 31.3 million per year in carbon reduction benefits from electric vehicle adoptions. This paper adds to the policy discussion of the costs of increased power outages due to extreme weather and natural disasters, and the urgency for policy to address this issue to facilitate wide adoption of electrification.

The actively heated fiber-optic (AHFO) technology has become emerged as a research focus due to its advantages of distributed, real-time measurement and good durability. These attributes have led to the gradual application of AHFO technology to the water content measurement of in situ soil. However, all existing in situ applications of AHFO technology fail to consider the effect of soil–sensor contact quality on water content measurements, limiting potential for the wider application of AHFO technology. To address this issue, the authors propose a method for determining the soil–sensor thermal contact resistance based on the principle of an infinite cylindrical heat source. This is then used to establish an AHFO water content measurement technology that considers the thermal contact resistance. The reliability and validity of the new measurement technology are explored through a laboratory test and a field case study, and the spatial-temporal evolution of the soil water content in the case is revealed. The results demonstrate that method for determining the soil–sensor thermal contact resistance is highly effective and applicable to all types of soils. This method requires only the moisture content, dry density, and thermal response of the in situ soil to be obtained. In the field case, the measurement error of soil water content between the AHFO method, which takes into account the thermal contact resistance, and the neutron scattering method is only 0.011. The water content of in situ soil exhibits a seasonal variation, with an increase in spring and autumn and a decrease in summer and winter. Furthermore, the response of shallow soils to precipitation and evaporation is significant. These findings contribute to the enhancement of the accuracy of the AHFO technology in the measurement of the water content of in situ soils, thereby facilitating the dissemination and utilization of this technology.

Abstract The association between the triglyceride-glucose (TyG) index and impaired fasting glucose (IFG) in elderly individuals remains uncertain. Our study aimed to explore the association between the TyG index and the risk of future IFG in this population. This retrospective cohort study included 17,746 elderly individuals over 60. In this population, Cox regression models proportional to hazards, along with smooth curve fitting and cubic spline functions, were employed to examine the association between the baseline TyG index and the risk of IFG. Subgroup analyses and sensitivity were also performed to ensure the robustness of the study findings. After adjusting for covariates, a positive association between the TyG index and the risk of IFG was found (HR = 1.43, 95% CI 1.27–1.60, P

Abstract Background Following spinal cord injury (SCI), the inflammatory storm initiated by microglia/macrophages poses a significant impediment to the recovery process. Exosomes play a crucial role in the transport of miRNAs, facilitating essential cellular communication through the transfer of genetic material. However, the miRNAs from iPSC-NSCs-Exos and their potential mechanisms leading to repair after SCI remain unclear. This study aims to explore the role of iPSC-NSCs-Exos in microglia/macrophage pyroptosis and reveal their potential mechanisms. Methods iPSC-NSCs-Exos were characterized and identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. A mouse SCI model and a series of in vivo and in vitro experiments were conducted to investigate the therapeutic effects of iPSC-NSCs-Exos. Subsequently, miRNA microarray analysis and rescue experiments were performed to confirm the role of miRNAs in iPSC-NSCs-Exos in SCI. Mechanistic studies were carried out using Western blot, luciferase activity assays, and RNA-ChIP. Results Our findings revealed that iPSC-NSCs-derived exosomes inhibited microglia/macrophage pyroptosis at 7 days post-SCI, maintaining myelin integrity and promoting axonal growth, ultimately improving mice motor function. The miRNA microarray showed let-7b-5p to be highly enriched in iPSC-NSCs-Exos, and LRIG3 was identified as the target gene of let-7b-5p. Through a series of rescue experiments, we uncovered the connection between iPSC-NSCs and microglia/macrophages, revealing a novel target for treating SCI. Conclusion In conclusion, we discovered that iPSC-NSCs-derived exosomes can package and deliver let-7b-5p, regulating the expression of LRIG3 to ameliorate microglia/macrophage pyroptosis and enhance motor function in mice after SCI. This highlights the potential of combined therapy with iPSC-NSCs-Exos and let-7b-5p in promoting functional recovery and limiting inflammation following SCI.

Abstract The clinical incidence of sjogren's syndrome combined with gastroesophageal reflux disease is high. Existing observational studies have shown inconsistent results in the association between gastroesophageal reflux disease (GERD) and Sjogren's syndrome (SS).We observed that the symptoms of SS patients also improved after receiving GERD-related treatment. Therefore, we aimed to investigate the relationship between GERD and SS through a bidirectional two-sample Mendelian randomization (MR) study. Independent SNPs associated with GERD and SS were selected from a genome-wide association study (GWAS) as instrumental variables to conduct a bidirectional two-sample Mendelian analysis of GERD and SS. Genetic data were obtained from two databases for the following two outcomes: Gastroesophageal reflux (IEU Open GWAS) [sample size = 602,604 (patients = 129,080; nonpatients = 473,524)] and SS (FinnGen) [sample size = 392,423 (patients = 2,495; nonpatients = 389,928)]. Statistical methods for the MR analysis included the inverse-variance weighting method, weighted median, simple mode and weighted mode, as well as heterogeneity and sensitivity analyses using the Cochran Q statistic, MR‒Egger regression, outlier detection methods (MR-PRESSO). In addition, Steiger Test was conducted to test the direction of causality. MR analysis showed a positive correlation between GERD and SS risk [odds ratio (OR) = 1.3279 (95% confidence interval 1.0312–1.7099, P = 0.0280)]. However, in contrast, no significant causal effect of SS on GERD was observed [OR = 1.0024 (95% CI 0.9651–1.0412; P = 0.8995)]. This bidirectional two-sample Mendelian randomization study confirmed a causal relationship between SS and GERD, and suggested that GERD is a risk factor for SS, while SS does not affect GERD.

Abstract Background The massive structural variations and frequent introgression highly contribute to the genetic diversity of wheat, while the huge and complex genome of polyploid wheat hinders efficient genotyping of abundant varieties towards accurate identification, management, and exploitation of germplasm resources. Results We develop a novel workflow that identifies 1240 high-quality large copy number variation blocks (CNVb) in wheat at the pan-genome level, demonstrating that CNVb can serve as an ideal DNA fingerprinting marker for discriminating massive varieties, with the accuracy validated by PCR assay. We then construct a digitalized genotyping CNVb map across 1599 global wheat accessions. Key CNVb markers are linked with trait-associated introgressions, such as the 1RS·1BL translocation and 2NvS translocation, and the beneficial alleles, such as the end-use quality allele Glu-D1d (Dx5 + Dy10) and the semi-dwarf r-e-z allele. Furthermore, we demonstrate that these tagged CNVb markers promote a stable and cost-effective strategy for evaluating wheat germplasm resources with ultra-low-coverage sequencing data, competing with SNP array for applications such as evaluating new varieties, efficient management of collections in gene banks, and describing wheat germplasm resources in a digitalized manner. We also develop a user-friendly interactive platform, WheatCNVb ( http://wheat.cau.edu.cn/WheatCNVb/ ), for exploring the CNVb profiles over ever-increasing wheat accessions, and also propose a QR-code-like representation of individual digital CNVb fingerprint. This platform also allows uploading new CNVb profiles for comparison with stored varieties. Conclusions The CNVb-based approach provides a low-cost and high-throughput genotyping strategy for enabling digitalized wheat germplasm management and modern breeding with precise and practical decision-making.

Abstract Background Lymphangioma is a rare cystic tumor that occurs across different locations. Retroperitoneal lymphangioma accounts for about 1% of all lymphangiomas. In this study, we report the clinicopathological features of retroperitoneal lymphangioma and describe our experience in treating this disease. Methods We collected clinical data from all patients who were pathologically diagnosed with retroperitoneal lymphangioma at Zhejiang Provincial People's Hospital, between June 2013 and August 2022. Results The 7 and 8 male and female patients analyzed herein had a mean age of 48.6 (SD 14.24) years at diagnosis. The mean duration of follow-up was 4.7 years. Among them, 66.67% were asymptomatic, with the rest manifesting abdominal pain, nausea, low back pain and elevated blood pressure as the main symptoms. Preoperative diagnosis and evaluation of cysts were mainly performed via computed tomography (CT) (n = 10, 66.67%) or magnetic resonance imaging (MRI) (n = 8, 53.33%). All patients were completely resected following surgery. Immunohistochemical analysis, performed on 6 patients, revealed that they were positive for D2-40. A total of 4, 4 and 3 patients were positive for CD31, CD34 and SMA, respectively. Moreover, the study cohort had an average postoperative hospital stay of 6.6 days. Follow up, after the end of the study, revealed no relapse in any of the 15 patients. Conclusions Lymphangioma is a benign tumor of the lymphatic system. Although typical imaging features can be accurate for preoperative diagnosis, histological examination is crucial to final confirmation. Complete surgical resection is the best option to limit the risk of recurrence in cases with symptomatic lesions.

Abstract Background Ovarian serous cystadenocarcinoma, accounting for about 90% of ovarian cancers, is frequently diagnosed at advanced stages, leading to suboptimal treatment outcomes. Given the malignant nature of the disease, effective biomarkers for accurate prediction and personalized treatment remain an urgent clinical need. Methods In this study, we analyzed the microbial contents of 453 ovarian serous cystadenocarcinoma and 68 adjacent non-cancerous samples. A univariate Cox regression model was used to identify microorganisms significantly associated with survival and a prognostic risk score model constructed using LASSO Cox regression analysis. Patients were subsequently categorized into high-risk and low-risk groups based on their risk scores. Results Survival analysis revealed that patients in the low-risk group had a higher overall survival rate. A nomogram was constructed for easy visualization of the prognostic model. Analysis of immune cell infiltration and immune checkpoint gene expression in both groups showed that both parameters were positively correlated with the risk level, indicating an increased immune response in higher risk groups. Conclusion Our findings suggest that microbial profiles in ovarian serous cystadenocarcinoma may serve as viable clinical prognostic indicators. This study provides novel insights into the potential impact of intratumoral microbial communities on disease prognosis and opens avenues for future therapeutic interventions targeting these microorganisms.

Abstract Background The spatial context of tumor-infiltrating immune cells (TIICs) is important in predicting colorectal cancer (CRC) patients’ clinical outcomes. However, the prognostic value of the TIIC spatial distribution is unknown. Thus, we aimed to investigate the association between TIICs in situ and patient prognosis in a large CRC sample. Methods We implemented multiplex immunohistochemistry staining technology in 190 CRC samples to quantify 14 TIIC subgroups in situ. To delineate the spatial relationship of TIICs to tumor cells, tissue slides were segmented into tumor cell and microenvironment compartments based on image recognition technology, and the distance between immune and tumor cells was calculated by implementing the computational pipeline phenoptr. Results MPO+ neutrophils and CD68+IDO1+ tumor-associated macrophages (TAMs) were enriched in the epithelial compartment, and myeloid lineage cells were located nearest to tumor cells. Except for CD68+CD163+ TAMs, other cells were all positively associated with favorable prognosis. The prognostic predictive power of TIICs was highly related to their distance to tumor cells. Unsupervised clustering analysis divided colorectal cancer into three subtypes with distinct prognostic outcomes, and correlation analysis revealed the synergy among B cells, CD68+IDO1+TAMs, and T lineage cells in producing an effective immune response. Conclusions Our study suggests that the integration of spatial localization with TIIC abundance is important for comprehensive prognostic assessment.

Abstract Background The safety and efficacy of vaccination against coronavirus disease 2019 (COVID-19) in patients with lymphangioleiomyomatosis (LAM) is still unclear. This study investigates COVID-19 vaccine hesitancy, vaccine safety and efficacy, and COVID-19 symptoms in LAM patients. Results In total, 181 LAM patients and 143 healthy individuals responded to the questionnaire. The vaccination rate of LAM patients was 77.34%, and 15.7% of vaccinated LAM patients experienced adverse events. Vaccination decreased the risk of LAM patients developing anorexia [OR: 0.17, 95% CI: (0.07, 0.43)], myalgia [OR: 0.34, 95% CI: (0.13, 0.84)], and ageusia [OR: 0.34, 95% CI: (0.14, 0.84)]. In LAM patients, a use of mTOR inhibitors reduced the risk of developing symptoms during COVID-19, including fatigue [OR: 0.18, 95% CI: (0.03, 0.95)], anorexia [OR: 0.30, 95% CI: (0.09, 0.96)], and ageusia [OR: 0.20, 95% CI: (0.06, 0.67)]. Conclusions Vaccination rates in the LAM population were lower than those in the general population, as 22.7% (41/181) of LAM patients had hesitations regarding the COVID-19 vaccine. However, the safety of COVID-19 vaccination in the LAM cohort was comparable to the healthy population, and COVID-19 vaccination decreased the incidence of COVID-19 symptoms in LAM patients. In addition, mTOR inhibitors seem not to determine a greater risk of complications in patients with LAM during COVID-19.

This study aims to validate the dosimetric characteristics of Low Dose Rate (LDR) I-125 source Geant4-based Monte Carlo code. According to the recommendation of the American Association of Physicists in Medicine (AAPM) task group report (TG-43), the dosimetric parameters of a new brachytherapy source should be verified either experimentally or theoretically before clinical procedures. The simulation studies are very important since this procedure delivers a high dose of radiation to the tumor with only a minimal dose affecting the surrounding tissues. GEANT4 Monte Carlo simulation toolkit associated brachytherapy example was modified, adapted and several updated techniques have been developed to facilitate and smooth radiotherapy techniques. The great concordance of the current study results with the consensus data and with the results of other MC based studies is promising. It implies that Geant4-based Monte Carlo simulation has the potential to be used as a reliable and standard simulation code in the field of brachytherapy for verification and treatment planning purposes.

Improving plant resistance to Verticillium wilt (VW), which causes massive losses in Gossypium hirsutum, is a global challenge. Crop plants need to efficiently allocate their limited energy resources to maintain a balance between growth and defense. However, few transcriptional regulators specifically respond to Verticillium dahliae and the underlying mechanism has not been identified in cotton. In this study, we found that the that expression of most R2R3-MYB members in cotton is significantly changed by V. dahliae infection relative to the other MYB types. One novel R2R3-MYB transcription factor (TF) that specifically responds to V. dahliae, GhMYB3D5, was identified. GhMYB3D5 was not expressed in 15 cotton tissues under normal conditions, but it was dramatically induced by V. dahliae stress. We functionally characterized its positive role and underlying mechanism in VW resistance. Upon V. dahliae infection, the up-regulated GhMYB3D5 bound to the GhADH1 promoter and activated GhADH1 expression. In addition, GhMYB3D5 physically interacted with GhADH1 and further enhanced the transcriptional activation of GhADH1. Consequently, the transcriptional regulatory module GhMYB3D5-GhADH1 then promoted lignin accumulation by improving the transcriptional levels of genes related to lignin biosynthesis (GhPAL, GhC4H, Gh4CL, and GhPOD/GhLAC) in cotton, thereby enhancing cotton VW resistance. Our results demonstrated that the GhMYB3D5 promotes defense-induced lignin accumulation, which can be regarded as an effective way to orchestrate plant immunity and growth.

Timely understanding of surrounding rock pressure bolting is crucial to enhance the service life of drilling rigs and ensure coal mine production safety. However, delayed feedback of drilling pressure, nonlinear distribution of coal and rock hardness,and inapplicability of existing methods in bolt support are common problems. To address these issues, a prediction method of drilling pressure in bolt support is proposed based on the optimal kernel function and historical points of Gaussian process time series regression. This is a machine learning method that is highly adaptabile to nonlinear problems and provides probabilistic output. It utilizes Gaussian stochastic process, kernel function, and Bayesian theory to predict the sequence coal rock pressure during bolt support. The optimal kernel function and historical points for the proposed prediction method were selected based on drilling pressure test data obtained during roadway excavation where the drill box was drilled 1000 mm. The parameters included 10 types of kernel functions (E, SE, RQ, Maten3/2, Maten5/2, ARDE, ARDSE, ARDRQ, ARDMatern3/2, ARDMatern5/2) and 7 different historical points (8, 10, 12, 14, 16, 18, 20). The optimal hyperparameter were adaptively determined through the negative logarithmic edge likelihood function as the minimization objective function. A total of 70 numerical calculations were performed using a single-step extrapolation method with a 7:3 ratio for the training and testing sets on the selected samples. Based on the evaluation indicators, such as determinability coefficient (R2), root mean square error (RMSE), and the average absolute error (MAE) of the test set, the optimal kernel function and optimal combination of duration points for four bolt support drilling pressure prediction strategies were identified. The optimal combination includes Matern5/2 with historical points 10, ARDMatern5/2 with historical points 10, SE with historical points 18, and RQ with historical points 18. The optimal kernel function was selected as Matern5/2 and the optimal number of historical points was chosen as 10, considering the minimization of computational complexity. Drilling pressure test data obtained from drilling the drill box at 1200 mm, 2400 mm and 3000 mm during the tunnel excavation process were used for numerical calculations The predicted distribution of the drilling pressure supported by the anchor rod was given with a 95% confidence interval. The proposed method achieved an R2 of 0.61317 and an MAE of 0.026957 for drilling pressure during drilling with a 1200 mm drill box, with an average width percentage of the interval of 3.072%. For the drilling pressure of 2400 mm drill box, the proposed method achieved an R2 of 0.93118 and an MAE of 0.010895, with an average width percentage of the interval of 0.581%. For the drilling pressure of 3000 mm drill box, the proposed method achieved an R2 of 0.99647 and an MAE of 0.0091847, with an average width percentage of the interval of 0.614%. The final conclusion found that the combination of different kernel functions and historical points has a significant difference in prediction performance,which is two important factors that cannot be ignored.The prediction results were excellent for the data bands with a uniform hardness distribution of the surrounding rock and acceptable for the data bands with abrupt hardness changes.

This study aimed to systematically evaluate the efficacy of liraglutide in treating type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) by comparing liraglutide with placebo or other drugs (mainly insulin). The PubMed, Web of Science, and National Library of Medicine databases were systematically searched from their inception until December 1, 2023. A meta-analysis was performed using Stata 15.1 software. A total of 12 studies with 13 outcome measures were included. The meta-analysis results revealed that liraglutide significantly reduced body mass index (mean difference [MD] = –1.06, 95%CI: –1.41, –0.70, p < 0.001), triglycerides (MD = –0.35, 95%CI: –0.61, –0.09, p = 0.0009), visceral adipose tissue (MD = –21.06, 95%CI: –34.58, –7.55, p = 0.002), and subcutaneous adipose tissue (MD = –20.53, 95%CI: –29.15, –11.90, p < 0.001) levels in patients with T2DM and NAFLD. Of the 11 studies, 2 reported the occurrence of adverse reactions, which were primarily gastrointestinal. Compared with placebo and other drugs (e.g., insulin), liraglutide may improve glucose metabolism, lipid and liver function parameters, and visceral and subcutaneous fat in patients with T2DM and NAFLD, thus constituting an effective treatment for these patients.

Abstract Background Gut microbiota is pivotal in regulating hosts' biological processes and maintaining homeostasis, but knowledge about its role in wild herbivores in extreme environments remains limited. Methods Gut bacteria and fungi were sequenced in ruminant (Chiru and Yak) and nonruminant (Kiang) herbivores on the Qinghai–Tibet Plateau, and their community structure, co‐occurrence networks, functions, and assembly mechanisms were investigated using multivariate ecological and statistical methods. Results Kiang had lower gut microbial diversity than Chiru and Yak. Bacterial host‐specific exclusivity was greater than that of fungi. In addition to the evidence of glycan biosynthesis and carbohydrate metabolism, Chiru had a high Firmicutes/Bacteroidetes ratio and low animal pathogen abundance, suggesting better adaptation to the plateau's harsh environment. Additionally, members of gut microbiota tended to co‐occur rather than co‐exclude in all herbivores. Different network complexity and stability patterns were observed between bacterial and fungal communities. Furthermore, gut bacterial assembly was primarily controlled by stochastic dispersal limitation and drift, whereas fungal assembly was primarily controlled by deterministic homogeneous selection except in Chiru. Conclusions On the Qinghai–Tibet Plateau, Chiru and Yak exhibit more diverse gut microbiota and more diverse metabolic functions than Kiang, and gut bacteria are more divergent than gut fungi in these herbivores.

Abstract Although robotic radical resection for hilar cholangiocarcinoma (HCCA) has been reported in some large hepatobiliary centers, biliary-enteric reconstruction (BER) remains a critical step that hampers the operation’s success. This study aimed to evaluate the feasibility and quality of BER in robotic radical resection of HCCA and propose technical recommendations. A retrospective study was conducted on patients with HCCA who underwent minimally invasive radical resection at Zhejiang Provincial People’s Hospital between January 2016 and July 2023. A 1:2 propensity score matching (PSM), widely used to reduce selection bias, was performed to evaluate the outcomes, especially BER-related data, between the robotic and laparoscopic surgery. Forty-six patients with HCCA were enrolled; ten underwent robotic-assisted resection, while the others underwent laparoscopic surgery. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robot-assisted and laparoscopic groups, respectively. The baseline characteristics of both groups were generally well-balanced. The average liver resection time was longer in the robotic group than in the laparoscopic group (139.5 ± 38.8 vs 108.1 ± 35.8 min, P = 0.036). However, the former had less intraoperative blood loss [200 (50–500) vs 310 (100–850) ml], despite no statistical difference (P = 0.109). The number of residual bile ducts was 2.6 ± 1.3 and 2.7 ± 1.2 (P = 0.795), and anastomoses were both 1.6 ± 0.7 in the two groups (P = 0.965). The time of BER was 38.4 ± 13.6 and 59.1 ± 25.5 min (P = 0.024), accounting for 9.9 ± 2.8% and 15.4 ± 4.8% of the total operation time (P = 0.001). Although postoperative bile leakage incidence in laparoscopic group (40%) was higher than that in robotic group (10%), there was no significant difference between the two groups (P = 0.204); 6.7 ± 4.4 and 12.1 ± 11.7 days were observed for tube drawing (P = 0.019); anastomosis stenosis and calculus rate was 10% and 30% (P = 0.372), 0% and 15% (P = 0.532), respectively. Neither group had hemorrhage- or bile leakage-related deaths. Robotic radical resection for HCCA may offer perioperative outcomes comparable to conventional laparoscopic procedures and tends to be advantageous in terms of anastomosis time and quality. We are optimistic about its wide application in the future with the improvement of surgical techniques and experience.

Abstract Background Nasopharyngeal carcinoma (NPC) is a type of malignant tumor with high morbidity. Aberrant levels of N7-methylguanosine (m7G) are closely associated with tumor progression. However, the characteristics of the tumor microenvironment (TME) in NPC associated with m7G modification remain unclear. Methods A total of 68,795 single cells from single-cell RNA sequencing data derived from 11 NPC tumor samples and 3 nasopharyngeal lymphatic hyperplasia (NLH) samples were clustered using a nonnegative matrix factorization algorithm according to 61 m7G RNA modification regulators. Results The m7G regulators were found differential expression in the TME cells of NPC, and most m7G-related immune cell clusters in NPC tissues had a higher abundance compared to non-NPC tissues. Specifically, m7G scores in the CD4+ and CD8+ T cell clusters were significantly lower in NPC than in NLH. T cell clusters differentially expressed immune co-stimulators and co-inhibitors. Macrophage clusters differentially expressed EIF4A1, and high EIF4A1 expression was associated with poor survival in patients with head and neck squamous carcinoma. EIF4A1 was upregulated in NPC tissues compared to the non-NPC tissues and mainly expressed in CD86+ macrophages. Moreover, B cell clusters exhibited tumor biological characteristics under the regulation of m7G-related genes in NPC. The fibroblast clusters interacted with the above immune cell clusters and enriched tumor biological pathways, such as FGER2 signaling pathway. Importantly, there were correlations and interactions through various ligand-receptor links among epithelial cells and m7G-related TME cell clusters. Conclusion Our study revealed tumor-associated characteristics and immune dysregulation in the NPC microenvironment under the regulation of m7G-related TME cells. These results demonstrated the underlying regulatory roles of m7G in NPC.

Abstract Background Despite effective strategies, resistance in EGFR mutated lung cancer remains a challenge. Metabolic reprogramming is one of the main mechanisms of tumor drug resistance. A class of drugs known as “statins” inhibit lipid cholesterol metabolism and are widely used in patients with cardiovascular diseases. Previous studies have also documented its ability to improve the therapeutic impact in lung cancer patients who receive EGFR-TKI therapy. Therefore, the effect of statins on targeted drug resistance to lung cancer remains to be investigated. Methods Prolonged exposure to gefitinib resulted in the emergence of a resistant lung cancer cell line (PC9GR) from the parental sensitive cell line (PC9), which exhibited a traditional EGFR mutation. The CCK-8 assay was employed to assess the impact of various concentrations of pitavastatin on cellular proliferation. RNA sequencing was conducted to detect differentially expressed genes and their correlated pathways. For the detection of protein expression, Western blot was performed. The antitumor activity of pitavastatin was evaluated in vivo via a xenograft mouse model. Results PC9 gefitinib resistant strains were induced by low-dose maintenance. Cell culture and animal-related studies validated that the application of pitavastatin inhibited the proliferation of lung cancer cells, promoted cell apoptosis, and restrained the acquired resistance to EGFR-TKIs. KEGG pathway analysis showed that the hippo/YAP signaling pathway was activated in PC9GR cells relative to PC9 cells, and the YAP expression was inhibited by pitavastatin administration. With YAP RNA interference, pAKT, pBAD and BCL-2 expression was decreased, while BAX expression as increased. Accordingly, YAP down-regulated significantly increased apoptosis and decreased the survival rate of gefitinib-resistant lung cancer cells. After pAKT was increased by SC79, apoptosis of YAP down-regulated cells induced by gefitinib was decreased, and the cell survival rate was increased. Mechanistically, these effects of pitavastatin are associated with the YAP pathway, thereby inhibiting the downstream AKT/BAD-BCL-2 signaling pathway. Conclusion Our study provides a molecular basis for the clinical application of the lipid-lowering drug pitavastatin enhances the susceptibility of lung cancer to EGFR-TKI drugs and alleviates drug resistance.