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Abstract Gliomas are aggressive brain tumors associated with poor prognosis and limited treatment options due to their invasive nature and resistance to current therapeutic modalities. Research suggests that exosomal microRNAs have emerged as key players in intercellular communication within the tumor microenvironment, influencing tumor progression and therapeutic responses. Exosomal microRNAs (miRNAs), small non-coding RNAs, are crucial in glioma development, invasion, metastasis, angiogenesis, and immune evasion by binding to target genes. This comprehensive review examines the clinical relevance and implications of exosomal miRNAs in gliomas, highlighting their potential as diagnostic biomarkers, therapeutic targets and prognosis biomarker. Additionally, we also discuss the limitations of current exsomal miRNA treatments and address challenges and propose future directions for leveraging exosomal miRNAs in precision oncology for glioma management.

Abstract Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in P. aeruginosa PAO1, PqsS, which promotes bacterial pathogenicity and pseudomonas quinolone signal quorum sensing (pqs QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed pqsL transcript, increasing PQS levels for pqs QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the pqsL mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on P. aeruginosa pathogenesis and targeted treatment.

In this work, the coordination chemistry of the uranyl ion(\begin{document}${\mathrm{UO}}_2^{2+} $\end{document}) with N, N-dimethyl-diglycolamic acid(HDMDGA, HLI) and N, N-diethyl-diglycolamic acid(HDEDGA, HLII) has been systematically studied through thermodynamic and structural analysis, by means of both potentiometric and spectroscopic titration, as well as Raman spectroscopy and X-ray diffractometry. The protonation constants of L−(L=LI, LII) and the stability constants of the uranyl complexes were determined by potentiometric and spectroscopic titrations in 1.0 mol/L NaClO4, with the molar absorption spectra of all species deconvoluted in the process of the latter titration. Besides, the standard Raman spectra of various complexes were confirmed by Raman spectroscopic titration. Furthermore, the single crystal of compound \begin{document}${\mathrm{UO}}_2{\mathrm{L}}^{{\mathrm{II}}}_2 $\end{document} was obtained by slow evaporation of aqueous solution containing uranyl ion and LII ligands at room temperature. X-ray diffraction analysis shows a monoclinic crystal system in P21/c space group, with lattice parameters: a=15.5096(6) Å（1 Å=0.1 nm）, b=7.7934(3) Å, c=11.3732(4) Å, α=90°, β=97.388(4)°, γ=90° and Z=2. Although both ligands show a similar structure and protonation constant, the different values of stability constant in aqueous solution and the different bond length of U-O in two complexes indicate the distinct coordination ability for two ligands with \begin{document}${\mathrm{UO}}_2^{2+} $\end{document}, where HDEDGA performs better. Like the crystal structure of \begin{document}$ {\mathrm{UO}}_2{\mathrm{L}}^{{\mathrm{I}}}_2$\end{document}, the ligand LII in the \begin{document}${\mathrm{UO}}_2{\mathrm{L}}^{{\mathrm{II}}}_2 $\end{document} complex coordinates with \begin{document}${\mathrm{UO}}_2^{2+} $\end{document} in a tridentate manner, with three oxygen atoms(amide oxygen, ether oxygen and carboxylic acid oxygen) coordinating with the linear \begin{document}${\mathrm{UO}}_2^{2+} $\end{document} at the equatorial plane. In addition, the diffuse reflectance spectra of the \begin{document}${\mathrm{UO}}_2{\mathrm{L}}^{{\mathrm{II}}}_2 $\end{document} crystal show characteristics significantly different from the absorption spectra of the corresponding complex in the aqueous solution. Meanwhile, the Raman shift of the characteristic peak of uranyl ion between hydrated uranyl ion and the 1∶1 complex(U∶ LII) is significantly larger than that between 1∶1 and 1∶2. Therefore, it is speculated that the structure of the 1∶2 complex in aqueous solution is supposed to be different from that in the solid crystal.

Abstract Background Previous studies have identified the hemoglobin (Hb) to red blood cell distribution width (RDW) ratio (HRR) is associated with the prognosis of a variety of malignant tumors. However, the relationship between HRR and pancreatic ductal adenocarcinoma (PDAC) prognosis remains unexplored. This study aims to ascertain the prognostic significance of HRR in PDAC patients. Methods In a retrospective analysis, 128 PDAC patients undergoing initial surgical resection at Ningbo Medical Center Lihuili Hospital between January 2016 and September 2021 were included. Based on receiver operating characteristic curve-derived cut-off values, participants were categorized into low and high HRR groups. The correlation between HRR and patient prognosis was subsequently examined. Results Significant disparities in age, Hb levels, RDW, tumor locality, surgical intervention, and postoperative chemotherapy were observed between the two groups (P

Abstract Malignant tumors remain a primary cause of human mortality. Among the various treatment modalities for neoplasms, tumor vaccines have consistently shown efficacy and promising potential. These vaccines offer advantages such as specificity, safety, and tolerability, with mRNA vaccines representing promising platforms. By introducing exogenous mRNAs encoding antigens into somatic cells and subsequently synthesizing antigens through gene expression systems, mRNA vaccines can effectively induce immune responses. Katalin Karikó and Drew Weissman were awarded the 2023 Nobel Prize in Physiology or Medicine for their great contributions to mRNA vaccine research. Compared with traditional tumor vaccines, mRNA vaccines have several advantages, including rapid preparation, reduced contamination, nonintegrability, and high biodegradability. Tumor-targeted therapy is an innovative treatment modality that enables precise targeting of tumor cells, minimizes damage to normal tissues, is safe at high doses, and demonstrates great efficacy. Currently, targeted therapy has become an important treatment option for malignant tumors. The application of mRNA vaccines in tumor-targeted therapy is expanding, with numerous clinical trials underway. We systematically outline the targeted delivery mechanism of mRNA vaccines and the mechanism by which mRNA vaccines induce anti-tumor immune responses, describe the current research and clinical applications of mRNA vaccines in tumor-targeted therapy, and forecast the future development trends of mRNA vaccine application in tumor-targeted therapy.

On September 17, 2020, a landslide occurred in Hongzhai Village, Jichang Town, Qinglong County, Guizhou Province, resulting in serious damage to 134 houses and emergency evacuation of 569 people from 127 households. Investigation revealed that the Hongzhai landslide is a deep-seated large-scale landslide with a volume of approximately 6.25×106 m3. Although surface buildings and infrastructure were severely damaged, the overall movement distance of the landslide was extremely short. Through comprehensive analysis including terrain geomorphology, rock and soil structure and material composition analysis, assessment of hydrological changes, and disclosure of multiple slip surfaces through borehole drilling, it was concluded that the Hongzhai landslide is a resurrected ancient landslide along bedding planes. In order to analyze and study the deformation characteristics and resurrection causes of the landslide, methods including UAV aerial survey, engineering geological survey, rock and soil mass investigation, and geophysical exploration were employed to obtain detailed data on disaster development characteristics, influencing factors, and identification features of ancient landslides. The results show that the Hongzhai landslide can be divided into four zones (A, B, C, D) based on deformation and stress transfer direction, with zone B further divided into subzones B1 and B2 based on relative displacement. The deformation and resurrection of the landslide occurred under the joint effects of steep terrain, complex rock mass structures, weak engineering rock masses, and continuous surface infiltration. Various features such as the arm-chair shaped topography at the back edge of the landslide, material differences between the slide body and surrounding rock and soil masses, fault-cutting front edges, and changes in hydrological sedimentation verify the existence of the ancient landslide.

Abstract We introduce University of Texas - GLObal Building heights for Urban Studies (UT-GLOBUS), a dataset providing building heights and urban canopy parameters (UCPs) for more than 1200 city or locales worldwide. UT-GLOBUS combines open-source spaceborne altimetry (ICESat-2 and GEDI) and coarse-resolution urban canopy elevation data with a machine-learning model to estimate building-level information. Validation using LiDAR data from six U.S. cities showed UT-GLOBUS-derived building heights had a root mean squared error (RMSE) of 9.1 meters. Validation of mean building heights within 1-km2 grid cells, including data from Hamburg and Sydney, resulted in an RMSE of 7.8 meters. Testing the UCPs in the urban Weather Research and Forecasting (WRF-Urban) model resulted in a significant improvement (55% in RMSE) in intra-urban air temperature representation compared to the existing table-based local climate zone approach in Houston, TX. Additionally, we demonstrated the dataset’s utility for simulating heat mitigation strategies and building energy consumption using WRF-Urban, with test cases in Chicago, IL, and Austin, TX. Street-scale mean radiant temperature simulations using the SOlar and LongWave Environmental Irradiance Geometry (SOLWEIG) model, incorporating UT-GLOBUS and LiDAR-derived building heights, confirmed the dataset’s effectiveness in modeling human thermal comfort in Baltimore, MD (daytime RMSE = 2.85°C). Thus, UT-GLOBUS can be used for modeling urban hazards with significant socioeconomic and biometeorological risks, enabling finer scale urban climate simulations and overcoming previous limitations due to the lack of building information.

The advent of cancer immunotherapy has imparted a transformative impact on cancer treatment paradigms by harnessing the power of the immune system. However, the challenge of practical and precise targeting of malignant cells persists. To address this, engineered nanoparticles (NPs) have emerged as a promising solution for enhancing targeted drug delivery in immunotherapeutic interventions, owing to their small size, low immunogenicity, and ease of surface modification. This comprehensive review delves into contemporary research at the nexus of NP engineering and immunotherapy, encompassing an extensive spectrum of NP morphologies and strategies tailored toward optimizing tumor targeting and augmenting therapeutic effectiveness. Moreover, it underscores the mechanisms that NPs leverage to bypass the numerous obstacles encountered in immunotherapeutic regimens and probes into the combined potential of NPs when co-administered with both established and novel immunotherapeutic modalities. Finally, the review evaluates the existing limitations of NPs as drug delivery platforms in immunotherapy, which could shape the path for future advancements in this promising field.

Abstract Staphylococcus aureus (SA) poses a serious risk to human and animal health, necessitating a low-cost and high-performance analytical platform for point-of-care diagnostics. Cellulose paper-based field-effect transistors (FETs) with RNA-cleaving DNAzymes (RCDs) can fulfill the low-cost requirements, however, its high hydrophilicity and lipophilicity hinder biochemical modification and result in low sensitivity, poor mechanical stability and poor fouling performance. Herein, we proposed a controllable self-cleaning FET to simplify biochemical modification and improve mechanical stability and antifouling performance. Then, we constructed an RCD-based DNA nanotree to significantly enhance the sensitivity for SA detection. For controllable self-cleaning FET, 1 H,1 H,2 H,2 H-perfluorodecyltrimethoxysilane based-polymeric nanoparticles were synthesized to decorate cellulose paper and whole carbon nanofilm wires. O2 plasma was applied to regulate to reduce fluorocarbon chain density, and then control the hydrophobic-oleophobic property in sensitive areas. Because negatively charged DNA affected the sensitivity of semiconducting FETs, three Y-shaped branches with low-cost were designed and applied to synthesize an RCD-based DNA-Nanotree based on similar DNA-origami technology, which further improved the sensitivity. The trunk of DNA-Nanotree was composed of RCD, and the canopy was self-assembled using multiple Y-shaped branches. The controllable self-cleaning FET biosensor was applied for SA detection without cultivation, which had a wide linear range from 1 to 105 CFU/mL and could detect a low value of 1 CFU/mL.

The fabrication of high quality copper alloys using laser powder bed fusion (LPBF) technology remains challenging due to their low laser absorption and high thermal conductivity. LPBF often involves intrinsic defects, such as rough surface and internal pores, which largely deteriorate the performance of as-built copper alloy components. Here we studied the effect of scanning speed on the evolution of surface morphologies and internal pores of LPBF-fabricated CuSn10 alloy. The melt flow behaviors were studied by both experiments and in situ observations where combined a high-speed camera with an infrared thermal imager. With increasing the scanning speed, the morphology of melt track evolves from a continuous track to a discontinuous one, whereas the internal defects change from a great number of spherical pores to many irregular pores. A higher scanning speed decreases the peak temperature of the melt pool and causes less overlaps between neighboring melt tracks, thus deteriorating wetting behaviors. It is expected that the obtained results are beneficial for guiding the additive manufacturing of copper alloy parts with high metallurgical quality and thus promoting their industrial applications.

The deprotonation of acetohydroxamic acid(AHA) and its coordination chemistry with uranyl ion(\begin{document}${\mathrm{UO}}_2^{2+ }$\end{document}) in 1.0 mol/L NaClO4 has been investigated with potentiometric titration and Raman spectroscopy at 25 ℃. For the first time, the deprotonations of AHA in aqueous solutions are quantitatively investigated with potentiometric titration method. It is found that in aqueous solution AHA acts as a monobasic acid and the protonation constants calculated to be pKa1=9.24±0.11(errors are given by the HyperQuad software fitting calculations). The determined pKa1 is in good agreement with the previously reported one-step protonation. In a wide pH range from acidic to basic aqueous solutions, the two step-wise protonation of AHA has been found, at the same time, the complexation of U(Ⅵ) with AHA has been re-visited. For AHA at different degrees of deprotonation, various complexes of U(Ⅵ) with AHA at ratios of U(Ⅵ) and AHA from 1∶1 to 1∶3 are recognized by potentiometric titration method. Amongst, the 1∶1 set of complexes consists of UO2A+ and UO2(OH)A, the 1∶2 includes UO2A2 and UO2(OH)\begin{document}${\mathrm{A}}_2^{-} $\end{document}, and the 1∶3 is composed of three complexes UO2\begin{document}${\mathrm{A}}_3^{-} $\end{document}, UO2(OH)\begin{document}${\mathrm{A}}_3^{2-} $\end{document} and UO2(OH)2\begin{document}${\mathrm{A}}_3^{3-} $\end{document}. There are maybe more complex species formed during the titrations, especially in very basic solutions, but those cannot be well quantitatively characterized due to their very low solubilities. The stability constants of the mentioned seven species have been determined by HyperQuad software, with the values of UO2A+ and UO2A2 in good consistence with those reported previously. All other five new-detected complexes are detected in solutions of relatively higher pH values. In the potentiometric titrations at relatively low AHA concentration, both protons of AHA can be deprotonated to form higher proportioned UO2(OH)A in comparison with UO2A2, which is an equal species to UO2A+ in term of releasing/consuming H+ during the titration process. At greatly excessive concentrations of AHA, three complexes, UO2A+, UO2A2, and UO2\begin{document}${\mathrm{A}}_3^{-} $\end{document} are successively formed with only one proton deprotonated A− as the pH being increased; further, two species, UO2(OH)\begin{document}${\mathrm{A}}_3^{2-} $\end{document} and UO2(OH)2\begin{document}${\mathrm{A}}_3^{3-} $\end{document}, are formed with partial of the ligands in the form of completely deprotonated (OH)A2−. The Raman spectroscopic titrations show that the Raman shift of O=U=O moves to lower wavenumbers with the increase in the number of ligands, with 849 cm−1, 828 cm−1 and 807 cm−1 corresponding to the three sets of U(Ⅵ) to AHA ratios of 1∶1, 1∶2, and 1∶3, respectively. Moreover, the results demonstrate that the effect of deprotonation on the Raman shifts of uranyl ion is negligible, but the effect on the Raman intensity is significant. The almost same step-wise Raman shifts at about 21 cm−1 for the three sets of complexes, 1∶1, 1∶2 and 1∶3, indicates a similar coordination mode for all the AHA ligands with different degrees of deprotonation, which provides informative hints for the structures of the complexes.

Neptunium is one of long-life radioelements, whose speciation in different condition of underground water and soil type, including the adsorption characteristics and adsorption mechanism on some soils, is a critical field. The adsorption behavior of Np(Ⅴ) on muscovite minerals was studied by combining theoretical calculations and static adsorption experiments, providing a reference for evaluating the safety of nuclear waste disposal sites in this work. The adsorption behavior of 239Np(Ⅴ) by different particle sizes of muscovite was studied using characterization methods such as X-ray diffraction(XRD), scanning electron microscopy(SEM), material specific surface area(BET), and NaI(Tl) gamma spectroscopy. Explored the effects of factors such as time, pH value, and the presence or absence of \begin{document}${\mathrm{CO}}_3^{2-} $\end{document} on the adsorption of Np(Ⅴ) by muscovite with different particle sizes. Combining density functional based on first principles, B3LYP was selected as the functional and 6-31G* as the basis group, and quantum chemical calculations were carried out to obtain the dissociation constant(pKa) values of the sites, in order to describe the electronic behavior of the skeleton structure. The experimental results show that different particle sizes of muscovite have an impact on the adsorption of Np(Ⅴ), and the presence or absence of \begin{document}${\mathrm{CO}}_3^{2-} $\end{document} in the environment also affect the adsorption distribution coefficient. However, as the particle size of muscovite decreases, more active sites are exposed, and the trend of adsorption distribution coefficient varies. Based on the SEM image and adsorption distribution coefficient curve, it can be seen that as the grinding mesh size of the sample increases, the end face increases, and even layered muscovite is peeled off. In the alkaline region, the adsorption distribution coefficient slightly increases, but the adsorption distribution coefficient is all less than 100. A small amount of Np(Ⅴ) is enriched in fine-grained to extremely fine-grained minerals, related to finer sediment. The adsorption of Np(Ⅴ) by muscovite is weak and not dominant. Np(Ⅴ) mainly migrates with groundwater in muscovite minerals.

Highlights Reduced graphene oxide/carbon foams (RGO/CFs) vdWs heterostructures are efficiently fabricated via a simple mixed-dimensional assembly strategy. Linkage effect of optimized impedance matching and enhanced dielectric loss abilities endows the excellent microwave absorption performances of RGO/CFs vdWs heterostructures. Multiple functions such as good corrosion resistance performances and outstanding thermal insulation capabilities can be integrated into RGO/CFs vdWs heterostructures.

Mastitis affects almost all mammals including humans and dairy cows. In the dairy industry, bovine mastitis is a disease with a persistently high incidence, causing serious losses to the health of cows, the quality of dairy products, and the economy of dairy farms. Although local udder infection caused by the invasion of exogenous pathogens into the mammary gland was considered the main cause of mastitis, evidence has been established and continues to grow, showing that nutrition factors and gastrointestinal microbiome (GM) as well as their metabolites are also involved in the development of mammary inflammatory response. Suboptimal nutrition is recognized as a risk factor for increased susceptibility to mastitis in cattle, in particular the negative energy balance. The majority of data regarding nutrition and bovine mastitis involves micronutrients. In addition, the dysbiotic GM can directly trigger or aggravate mastitis through entero-mammary gland pathway. The decreased beneficial commensal bacteria, lowered bacterial diversity, and increased pathogens as well as proinflammatory metabolites are found in both the milk and gastrointestinal tract of mastitic dairy cows. This review discussed the relationship between the nutrition (energy and micronutrient levels) and mastitis, summarized the role of GM and metabolites in regulating mastitis. Meanwhile, several non-antibiotics strategies were provided for the prevention and alleviation of mastitis, including micronutrients, probiotics, short-chain fatty acids, high-fiber diet, inulin, and aryl hydrocarbon receptor.

With the continuous improvement of living standards, people are concerned about not only whether foods are tasty or not, but also the combination of health elements and good flavor. Food flavor components are not only important factors in sensory quality, but also key indicators of the nutritional level of foods. At present, the traditional methods to evaluate and predict food flavor components are time-consuming and labor-intensive, and unable to handle large amounts of data. In contrast, machine learning (ML), the core of artificial intelligence, has incomparable advantages over traditional analytical techniques in distinguishing differences and finding commonalities, and has found good application in the field of food flavor analysis. In this context, this paper focuses on the current research status of ML in the field of food flavor, and introduces the principles and advantages of commonly used ML methods, as well as their latest applications and prospects in food flavor prediction and regulation. It also focuses on the advantages and future trends of modern intelligent sensory evaluation techniques combined with ML in the field of food flavor analysis, with a view to providing new ideas and theoretical foundations for food flavor analysis and prediction.

Objective Bedding deep cutting slopes containing weak interlayers are commonly found in slope engineering, whose stability is influenced by two key factors: The strength of the sliding zone soil and the reserved thickness of the base (the distance from the base of an excavated slope to the weak interlayer). Methods In this research, taking the K42 cutting slope of the Yang-Xuan Expressway as an example, the evolution process of slope deformation was analyzed, especially the characteristics of basal heave deformation. The properties of the deep sliding zone soil in the slope were revealed by ring shear tests, which are suitable for studying the shear strength of soil that has experienced large shear displacements. Moreover, the residual strength parameters of the saturated sliding zone soil were applied to analyze the reserved thickness of the base. Results The results show that sliding zone soils exhibit obvious strain softening characteristics, which become more evident as the normal stress decreases. As the soil shear strength transitions from peak strength to residual strength, both the cohesion force and internal friction angle decrease, with the cohesion force decreasing to a greater extent than the internal friction angle. The residual cohesion force of sliding zone soil varies slightly with the shear rate, while the relationship between the residual internal friction angle and shear rate varies as a logarithmic function. When the shear rate is less than 2 mm/min, the residual shear strength parameter of sliding zone soil is more sensitive to the shear rate and vice versa. Conclusion Furthermore, according to the regression equations of the critical states of slope stability, the reserved thickness of the base under different slope rates was divided into four zones: A (extremely unstable zone), B (unstable zone), C (basically stable zone) and D (stable zone), and based on this, the criterion and early warning model of the reserved thickness of the base for slope excavation were established.

Abstract Climate change and disease threaten shrimp farming. Here, we studied the beneficial properties of a phytogenic formulation, Shrimp Best (SB), in whiteleg shrimp. Functional studies showed that SB dose-dependently increased shrimp body weight and decreased feed conversion ratio. We found that SB protected against Vibrio parahaemolyticus as evidenced by survival rate, bacterial load, and hepatopancreatic pathology in shrimp. Finally, we explored the likely mechanism by which SB affects growth performance and vibriosis in shrimp. The 16S rRNA sequencing data showed that SB increased 6 probiotic genera and decreased 6 genera of pathogenic bacteria in shrimp. Among these, SB increased the proportion of Lactobacillus johnsonii and decreased that of V. parahaemolyticus in shrimp guts. To dissect the relationship among SB, Lactobacillus and Vibrio, we investigated the in vitro regulation of Lactobacillus and Vibrio by SB. SB at ≥ 0.25 μg/mL promoted L. johnsonii growth. Additionally, L. johnsonii and its supernatant could inhibit V. parahaemolyticus. Furthermore, SB could up-regulate five anti-Vibrio metabolites of L. johnsonii, which caused bacterial membrane destruction. In parallel, we identified 3 fatty acids as active compounds from SB. Overall, this work demonstrated that SB improved growth performance and vibriosis protection in shrimp via the regulation of gut microbiota.

Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.

BackgroundModerately differentiated gastric adenocarcinoma (MDGA) has a high risk of metastasis and individual variation, which strongly affects patient prognosis. Using large-scale datasets and machine learning algorithms for prediction can improve individualized treatment. The specific efficacy of several lymph node indicators in predicting distant metastasis (DM) and patient prognosis in MDGA remains obscure.MethodsWe collected data from MDGA patients from the SEER database from 2010 to 2019. Additionally, we collected data from MDGA patients in China. We used nine machine learning algorithms to predict DM. Subsequently, we used Cox regression analysis to determine the risk factors affecting overall survival (OS) and cancer-specific survival (CSS) in DM patients and constructed nomograms. Furthermore, we used logistic regression and Cox regression analyses to assess the specific impact of six lymph node indicators on DM incidence and patient prognosis.ResultsWe collected data from 5,377 MDGA patients from the SEER database and 109 MDGC patients from hospitals. T stage, N stage, tumor size, primary site, number of positive lymph nodes, and chemotherapy were identified as independent risk factors for DM. The random forest prediction model had the best overall predictive performance (AUC = 0.919). T stage, primary site, chemotherapy, and the number of regional lymph nodes were identified as prognostic factors for OS. Moreover, T stage, number of regional lymph nodes, primary site, and chemotherapy were also influential factors for CSS. The nomograms showed good predictive value and stability in predicting the 1-, 3-, and 5-year OS and CSS in DM patients. Additionally, the log odds of a metastatic lymph node and the number of negative lymph nodes may be risk factors for DM, while the regional lymph node ratio and the number of regional lymph nodes are prognostic factors for OS.ConclusionThe random forest prediction model accurately identified high-risk populations, and we established OS and CSS survival prediction models for MDGA patients with DM. Our hospital samples demonstrated different characteristics of lymph node indicators in terms of distant metastasis and prognosis.

BackgroundReactivate the T cell immunity by PD-1/PD-L1 checkpoint blockade is widely used in non-small cell lung cancer (NSCLC) patients, while the post-translational modification of Programmed death ligand-1 (PD-L1) is commonly existed in various cancer cells, thus increases the complexity and difficulty in therapy development. Ginsenoside Rg3 is an active component of traditional Chinese herb Ginseng with multiple pharmacological effects including immune regulation. However, the effect on the glycosylation of PD-L1 is unknown.MethodsNSCLC cell lines were tested for glycosylation of PD-L1, and the potential mechanisms were investigated. Tumor cell-T cell coculture experiment was conducted and the activation of T cells and cytotoxicity were measured by flow cytometry. In vivo xenograft mouse tumor model was used to investigate the effects of Rg3 on PD-L1-mediated immunosuppression and tumor growth.ResultsHere, we identified PD-L1 is widely N-linked glycosylated in NSCLC cell lines, while Rg3 could inhibit the glycosylation of PD-L1 by downregulating the EGFR signaling and further activate GSK3b-mediated degradation, thus resulted in reduced PD-L1 expression. Moreover, the inhibition of PD-L1 glycosylation promoted the activation and cytotoxicity of T cells under coculture condition. In addition, Rg3 could decrease the tumor volume and enhance anti-tumor T cell immunity as evidence by the upregulated expression of Granzyme B and perforin in CD8+T cells, along with elevated serum IL-2, IFN-g and TNF-a level in Rg3-treated mice.ConclusionsThese results suggest that Rg3 inhibits PD-L1 glycosylation and thus enhance anti-tumor immunity, which provide new therapeutic insight into drug discovery.

Abstract Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer's disease (AD) risk; however, the underlying mechanisms are not fully understood. Here, it is found that the injection of chondroitinase ABC (ChABC), mimicking ECM remodeling, into the medial prefrontal cortex (mPFC) reversed short‐term memory loss and reduced amyloid‐beta (Aβ) deposition in 5xFAD mice. ECM remodeling also reactivated astrocytes, reduced the levels of aggrecan in Aβ plaques, and enhanced astrocyte recruitment to surrounding plaques. Importantly, ECM remodeling enhanced the autophagy‐lysosome pathway in astrocytes, thereby mediating Aβ clearance and alleviating AD pathology. ECM remodeling also promoted Aβ plaque phagocytosis by astrocytes by activating the astrocytic phagocytosis receptor MERTK and promoting astrocytic vesicle circulation. The study identified a cellular mechanism in which ECM remodeling activates the astrocytic autophagy‐lysosomal pathway and alleviates AD pathology. Targeting ECM remodeling may represent a potential therapeutic strategy for AD and serve as a reference for the treatment of this disease.

ABSTRACTThe order Agaricales was divided into eight suborders. However, the phylogenetic relationships among some suborders are largely unresolved, and the phylogenetic positions and delimitations of some taxa, such as Sarcomyxaceae and Tricholomopsis, remain unsettled. In this study, sequence data of 38 genomes were generated through genome skimming on an Illumina sequencing system. To anchor the systematic position of Sarcomyxaceae and Tricholomopsis, a phylogenetic analysis based on 555 single-copy orthologous genes from the aforementioned genomes and 126 publicly accessible genomes was performed. The results fully supported the clustering of Tricholomopsis with Phyllotopsis and Pleurocybella within Phyllotopsidaceae, which formed a divergent monophyletic major lineage together with Pterulaceae, Radulomycetaceae, and Macrotyphula in Agaricales. The analysis also revealed that Sarcomyxaceae formed a unique major clade. Therefore, two new suborders, Phyllotopsidineae and Sarcomyxineae, are proposed for the two major lineages. Analyses of 450 single-copy orthologous genes and four loci suggested that Tricholomopsis consisted of at least four clades. Tricholomopsis is subsequently subdivided into four distinct sections. Seventeen Tricholomopsis species in China, including six new species, are reported. Conoloma is established to accommodate T. mucronata. The substrate preference of Tricholomopsis species and the transitions of the pileate ornamentations among the species within the genus are discussed.

Abstract Background Bronchial arterial embolization (BAE) has been accepted as an effective treatment for bronchiectasis-related hemoptysis. However, rare clinical trials compare different sizes of specific embolic agents. This study aims to evaluate whether different Embosphere microsphere sizes change the outcome of BAE. Methods A retrospective review was conducted on consecutive patients with bronchiectatic hemoptysis who were scheduled to undergo BAE treatment during a period from January 2018 to December 2022. The patients received BAE using microspheres of different sizes: group A patients were treated with 500–750 μm microspheres, and group B patients were treated with 700–900 μm microspheres. The cost of embolic microspheres (Chinese Yuan, CNY), duration of hospitalization, complications, and hemoptysis-free survival were compared between patients in group A and those in group B. A Cox proportional hazards regression model was used to identify predictors of recurrent hemoptysis. Results Median follow-up was 30.2 months (range, 20.3–56.5 months). The final analysis included a total of 112 patients (49–77 years of age; 45 men). The patients were divided into two groups: group A (N = 68), which received 500–750 μm Embosphere microspheres, and group B (N = 44), which received 700–900 μm Embosphere microspheres. Except for the cost of embolic microspheres(group A,5314.8 + 1301.5 CNY; group B, 3644.5 + 1192.3 CNY; p = 0.042), there were no statistically significant differences in duration of hospitalization (group A,7.2 + 1.4 days; group B, 8 + 2.4days; p = 0.550), hemoptysis-free survival (group A, 1-year, 2-year, 3-year, 85.9%, 75.8%, 62.9%; group B, 1-year, 2-year, 3-year, 88.4%, 81.2%,59.4%;P = 0.060), and complications(group A,26.5%; group B, 38.6%; p = 0.175) between the two groups. No major complications were observed. The multivariate analysis results revealed that the presence of cystic bronchiectasis (OR 1.61, 95% CI 1.12–2.83; P = 0.001) and systemic arterial-pulmonary shunts (SPSs) (OR 1.52, 95% CI 1.10–2.72; P = 0.028) were independent risk factors for recurrent bleeding. Conclusions For the treatment of BAE in patients with bronchiectasis-related hemoptysis, 500–750 μm diameter Embosphere microspheres have a similar efficacy and safety profile compared to 700–900 μm diameter Embosphere microspheres, especially for those without SPSs or cystic bronchiectasis. Furthermore, the utilization of large-sized (700–900 μm) Embosphere microspheres is associated with the reduced cost of an embolic agent.

Under the trend of deep mining of coal resources, the problem of high temperature heat damage in mines is becoming increasingly serious, the heat source that causes high temperature heat damage in mines is actually sustainably used geothermal energy, extracting and utilizing geothermal energy from deep mines while mining coal is an innovative way to build green mines and reduce mine carbon dioxide emission. This paper summarizes the current situation of deep mineral and geothermal energy collaborative exploration at China and abroad, analyzes the feasibility in terms of processes and key equipment and finally proposes a system of coal-geothermal collaborative exploration. The system adopts closed cycle mode, including ground heat utilization system and underground extracting system, drilling horizontal holes and installing coaxial casing heat exchangers at the coal to extract the heat, and utilization of the extracted low-grade geothermal energy through the heat pump on ground. Adhering to the principle of “mining heat first and then mining” in terms of time and space coordination, the thermal mining face is divided in front of the mining work in advance, and two modes of sequential and alternating thermal mining are proposed to ensure that the thermal mining process does not interfere with the coal mining process. Analyzed key technologies including spatial collaborative design, coal seam drilling, efficient heat extraction, and intelligent monitoring and control. Conducted underground spatial collaborative design for coal mining and geothermal energy extraction, proposed a coaxial casing heat exchanger layout process based on coal seam water injection. Multiple combinations of quick assembly coaxial casing heat exchangers can be used to achieve efficient heat extraction. Building an intelligent monitoring and control platform and proposed relevant optimization models, building a heat extraction calculation model and propose an intelligent control heat extraction method. Simplify the heat transfer process of coal formations, construct a heat transfer model for heat extraction from coal to calculate and evaluate the heat capacity of the mining face based on its actual situation and the outlet airflow parameters. According to the heat transfer model, the initial temperature of coal, the coal transportation volume, and the outlet air flow temperature through mining face are the key parameters that determine the heat extraction from the coal. The heat extraction is the maximum when the moisture content of the air flow of the working face remains unchanged and the equivalent temperature of the air flow at the outlet of the working face is not higher than 28 ℃. The application of this system will converting heat damage of deep mine to useful resources, which not only solves the problem of heat damage of coal mining, but also realizes the comprehensive utilization of geothermal energy in deep mine.

Two new termite-pathogenic species, Ophiocordyceps globiperitheciata and O. longistipes, are described from Yunnan Province, China. Six-locus (ITS, nrSSU, nrLSU, tef-1α, rpb1 and rpb2) phylogenetic analyses in combination with morphological observations were employed to characterize these two species. Phylogenetically, O. globiperitheciata is most closely related to Hirsutella cryptosclerotium and O. communis, whereas O. longistipes shares a sister relationship with O. fusiformis. However, O. globiperitheciata differs from H. cryptosclerotium by parasitizing Blattodea and producing clavate, unbifurcated stromata. Ophiocordyceps globiperitheciata is distinguished from O. communis by multiple stromata, shorter asci and ascospores. Ophiocordyceps longistipes differs from O. fusiformis in producing larger stromata, perithecia, asci and ascospores, as well as smaller citriform or oval conidia. Morphological descriptions of the two new species and a dichotomous key to the 19 termite-pathogenic Ophiocordyceps species are presented.

Objectives: We characterized the population structure and features of clinical Streptococcus pneumoniae isolates associated with invasive pneumococcal disease (IPD) from 2009 to 2017 in a Chinese metropolitan city using a whole-genome sequencing approach. Methods: Seventy-nine pneumococcal strains, including 60 serogroup-19 strains from children enduring IPD from a paediatric hospital in Shenzhen, were subjected to whole-genome sequencing. Population structure was characterized through phylogenetic analysis, sequence typing, serotyping, virulence factor, and antimicrobial drug resistance (AMR) gene profiling, combining the publicly available related WGS data. Clinical demography and antibiotic susceptibility profiles were compared among different populations to emphasize the higher-risk populations. Genetic regions associated with AMR gene mobilization were identified through comparative genomics. Results: These IPD strains mainly belonged to clonal complex 320 (CC320) and were composed of serotypes 19A and 19F. In addition to sporadic possible importation-related isolates (ST320), we identified an independent clade, CC320_SZpop (ST271), that predominantly circulated in Shenzhen and possibly expanded its range. Clinical features and antibiotic susceptibility analysis revealed that CC320_SZpop might manifest much higher pathogenicity and tolerance to β-lactams. Specific virulence factors in Shenzhen isolates of CC320_SZpop were identified. Furthermore, an ca. 40 kb hotspot genomic region enduring frequent recombination was identified, possibly associated with the divergence of S. pneumoniae strains. Conclusion: A novel pneumococcal clade, CC320_SZpop, circulating in Shenzhen and other regions in China, possibly under expansion, was found and deserves more study and surveillance. Our study also emphasizes the importance of continuous genomic surveillance of clinical S. pneumoniae isolates, especially IPD isolates.

Abstract Chronic wounds are often infected with biofilm bacteria and characterized by high oxidative stress. Current dressings that promote chronic wound healing either require additional processes such as photothermal irradiation or leave behind gross amounts of undesirable residues. We report a dual-functionality hydrogel dressing with intrinsic antibiofilm and antioxidative properties that are synergistic and low-leaching. The hydrogel is a crosslinked network with tethered antibacterial cationic polyimidazolium and antioxidative N-acetylcysteine. In a murine diabetic wound model, the hydrogel accelerates the closure of wounds infected with methicillin-resistant Staphylococcus aureus or carbapenem-resistant Pseudomonas aeruginosa biofilm. Furthermore, a three-dimensional ex vivo human skin equivalent model shows that N-acetylcysteine promotes the keratinocyte differentiation and accelerates the re-epithelialization process. Our hydrogel dressing can be made into different formats for the healing of both flat and deep infected chronic wounds without contamination of the wound or needing other modalities such as photothermal irradiation.

This paper aimed to explore the correlation between the physical and chemical indicators of sauce-flavor Daqu with different sensory characteristics and the community of molds, six physical and chemical indicators of WQ, YQ and BQ were tested, the mold of Daqu were separated and identified, the correlation between the physical and chemical indicators and mold community in three kinds of Daqu were analyzed by redundancy analysis. The results showed that the liquefaction power of YQ was higher, and YQ and BQ showed the higher fermentation power and esterification power, respectively: 1.56 U, 22.63 U and 1.51 U, 22.48 U. A total of 78 strains of 13 species of molds belonging to 6 genera were isolated and identified from three kinds of Daqu, including 7 species in WQ, namely Paecilomyces subglobosus, Paecilomyces variotii, Lichtheimia corymbifera, Lichtheimia ornata, Penicillium tardochrysogenum, Penicillium chrysogenum, Epicoccum endophytica. 6 Species were isolated from YQ, namely Lichtheimia ramosa, Lichtheimia corymbifera, Paecilomyces variotii, Lichtheimia hongkongensis, Lichtheimia ornata, Aspergillus intermedius. 7 Species were isolated from BQ, namely Paecilomyces variotii, Paecilomyces subglobosus, Lichtheimia ramosa, Scopulariopsis brevicaulis, Lichtheimia corymbifera, Aspergillus sydowii, Aspergillus quadrilineatus. Through redundancy analysis, it was concluded that Lichtheimia was the main strain affecting the saccharification and esterification of Daqu. This study provides a basis for the research and application of molds in sauce-flavored Daqu and provides data support for improving the fermentation performance of sauce-flavored Daqu.