Investigation of relationships between metabolic chemical reporter structures and S-glyco-modification effects.

The approach of metabolic chemical reporters (MCRs) for labeling proteins has been widely used in the past several decades. Nevertheless, artificial side reaction generated with fully protected MCRs, termed S-glyco-modification, occurs with cysteine residues through base-promoted ß-elimination and Michael addition, leading to false positives in the proteomic identification. Therefore, next generation of MCRs, including partially protected strategy and modifications on the backbone of monosaccharides, have emerged to improve the labeling efficiency. In this paper, we prepared fifteen kinds of unnatural monosaccharides to investigate the relationships of structures and S-glyco-modification labeling. Our results demonstrated that Ac4GlcNAz and Ac4GalNAz exhibited the most remarkable labeling effects among the detected compounds. Of note, Ac4ManNAz, Ac46AzGlucose and Ac46AzGalactose containing similar structures but did not show similar robust signals as them. Moreover, other modifications on the 1-, 2-, 3-, 4- and 6-site indicated minimal side reactions of S-glyco-modification, raising a possibility that subtle modifications of monosaccharide substrate may alter its role in the process of biosynthesis, for example, by change of electronegativity or enhancement of steric hindrance effects. In conclusion, our discoveries provide a new avenue to choose appropriate probe for selective label proteins in vitro and in vivo without undesired S-glyco-modification.

Microbiome-host interactions in the pathogenesis of acute exacerbation of chronic obstructive pulmonary disease.

Objective: To explore the underlying mechanisms the airway microbiome contributes to Acute Exacerbation of Chronic Obstructive Pulmonary Disease(AECOPD). Methods: We enrolled 31 AECOPD patients and 26 stable COPD patients, their sputum samples were collected for metagenomic and RNA sequencing, and then subjected to bioinformatic analyses. The expression of host genes was validated by Quantitative Real-time PCR(qPCR) using the same batch of specimens. Results: Our results indicated a higher expression of Rothia mucilaginosa(p=0.015) in the AECOPD group and Haemophilus influenzae(p=0.005) in the COPD group. The Different expressed genes(DEGs) detected were significantly enriched in "type I interferon signaling pathway"(p<0.001, q=0.001) in gene function annotation, and "Cytosolic DNA-sensing pathway"(p=0.002, q=0.024), "Toll-like receptor signaling pathway"(p=0.006, q=0.045), and "TNF signaling pathway"(p=0.006, q=0.045) in KEGG enrichment analysis. qPCR amplification experiment verified that the expression of OASL and IL6 increased significantly in the AECOPD group. Conclusion: Pulmonary bacteria dysbiosis may regulate the pathogenesis of AECOPD through innate immune system pathways like type I interferon signaling pathway and Toll-like receptor signaling pathway.

Fungal community determines soil multifunctionality during vegetation restoration in metallic tailing reservoir.

Microorganisms are pivotal in sustaining soil functions, yet the specific contributions of bacterial and fungal succession on the functions during vegetation restoration in metallic tailing reservoirs remains elusive. Here, we explored bacterial and fungal succession and their impacts on soil multifunctionality along a ∼50-year vegetation restoration chronosequence in China's largest vanadium titano-magnetite tailing reservoir. We found a significant increase in soil multifunctionality, an index comprising factors pertinent to soil fertility and microbially mediated nutrient cycling, along the chronosequence. Despite increasing heavy metal levels, both bacterial and fungal communities exhibited significant increase in richness and network complexity over time. However, fungi demonstrated a slower succession rate and more consistent composition than bacteria, indicating their relatively higher resilience to environmental changes. Soil multifunctionality was intimately linked to bacterial and fungal richness or complexity. Nevertheless, when scrutinizing both richness and complexity concurrently, the correlations disappeared for bacteria but remained robust for fungi. This persistence reveals the critical role of the fungal community resilience in sustaining soil multifunctionality, particularly through their stable interactions with powerful core taxa. Our findings highlight the importance of fungal succession in enhancing soil multifunctionality during vegetation restoration in metallic tailing reservoirs, and manipulating fungal community may expedite ecological recovery of areas polluted with heavy metals.

[Effect of different initial processing treatments on commercial characters and chemical components of Fritillaria taipaiensis].

To investigate the effects of different initial processing methods on the quality of Fritillaria taipaiensis, this study explored the effects of anti-browning treatment, drying methods, and drying temperatures on the commercial characters, chromaticity values, and alkaloid and nucleoside components of Fritillariae Taipaiensis Bulbus. The results were comprehensively evaluated through correlation analysis(CA), principal component analysis(PCA), and hierarchical clustering analysis(HCA). Compared with those of the direct drying group(WD60), the chromaticity values(ΔE*) of the groups with scraped outer skin( FHB1) and mixed lime powder treatments(FHB2) were significantly reduced, indicating the inhibition of the browning process. The total alkaloid content of the group with mixed raw soil treatment(FHB3) and the FHB2 group showed no significant change, whereas that of the group with 5%Na Cl O solution rinse treatment(FHB4) was the lowest. Compared with air-blast dried(WD50) samples, the ΔE* values of freezedried(FS6) and vacuum-dried(FS5) samples were significantly decreased, with an increase in total alkaloid contents. Conversely,the ΔE* values of shade-dried(FS1) and sun-dried(FS2) samples were significantly increased, with severe browning and low total alkaloid contents. The total alkaloid contents of heat-pump-dried(FS4) samples showed no significant change, and their ΔE* value was significantly decreased, with a light degree of browning and favorable commercial characters. The total alkaloid content of air-blast dried samples initially increased and then decreased within the range of 40-80 ℃, and the highest content was recorded at 70 ℃. The ΔE* values of high-temperature air-blast dried samples(70-80 ℃) were smaller with a light degree of browning, whereas their texture was compact and lacked powder. CA revealed a significant relationship between the uracil content and chromaticity value of the samples(P< 0. 05). The clustering relationships among samples subjected to different treatments were visualized via PCA and HCA. The results showed that FHB2 and air-blast drying(50-60 ℃) were more suitable for large-scale production, and heat pump drying could be a promising direction for future development. This study provides a scientific basis for optimizing the initial processing methods of Fritillaria taipaiensis.

Microbial nutrient limitation and carbon use efficiency changes under different degrees of litter decomposition.

Alpine ecosystems are important terrestrial carbon (C) pools, and microbial decomposers play a key role in litter decomposition. Microbial metabolic limitations in these ecosystems, however, remain unclear. The objectives of this study aim to elucidate the characteristics of microbial nutrient limitation and their C use efficiency (CUE), and to evaluate their response to environmental factors. Five ecological indicators were utilized to assess and compare the degree of microbial elemental homeostasis and the nutrient limitations of the microbial communities among varying stages of litter decomposition (L, F, and H horizon) along an altitudinal gradient (2800, 3000, 3250, and 3500 m) under uniform vegetation (Abies fabri) on Gongga Mountain, eastern Tibetan Plateau. In this study, microorganisms in the litter reached a strictly homeostatic of C content exclusively during the middle stage of litter decomposition (F horizon). Based on the stoichiometry of soil enzymes, we observed that microbial N- and P-limitation increased during litter degradation, but that P-limitation was stronger than N-limitation at the late stages of degradation (H horizon). Furthermore, an increase in microbial CUE corresponded with a reduction in microbial C-limitation. Additionally, redundancy analysis (RDA) based on forward selection further showed that microbial biomass C (MBC) is closely associated with the enzyme activities and their ratios, and MBC was also an important factor in characterizing changes in microbial nutrient limitation and CUE. Our findings suggest that variations in MBC, rather than N- and P-related components, predominantly influence microbial metabolic processes during litter decomposition on Gongga Mountain, eastern Tibetan Plateau.

Investigation of canopy interception characteristics in slope protection grasses: A laboratory experiment.

Canopy interception significantly affects hydrological processes such as infiltration, runoff and evapotranspiration. Research on grass canopy interception remains limited, and the experimental methods employed differ substantially. To thoroughly investigate the canopy interception characteristics of grass and clarify the methodological differences, five commonly utilized slope protection grass species in temperate regions were cultivated in a laboratory setting, and their canopy interception characteristics were experimentally investigated using the water-balance method (WBM), the water-wiping method (WWM) and the water-immersion method (WIM), respectively. The results showed that the WBM is more accurate for measuring canopy interception in grass, whereas both the WWM and the WIM underestimate grass canopy interception capacity. The canopy interception capacity measured by the WBM was 1.61-2.09 times higher than that of the WWM and 1.93-3.47 times higher than that of the WIM. Grey correlation analysis of the eight evaluated factors indicated that leaf area is the most influential factor affecting canopy interception in grass, followed by rainfall amount, dry mass, rainfall intensity, canopy projection area, leaf contact angle, fresh weight, and average height. There is a negative power function relationship between the interception ratio and the rainfall amount. With increasing rainfall intensity, the canopy interception capacity initially increases and then decreases, peaking at rainfall intensities of 15 to 20 mm/h. Leaf contact angle is a key quantifiable parameter that explains the differences in canopy interception among different grass species, and the canopy interception per unit leaf area decreases as the leaf contact angle increases. This study demonstrates that the WBM provides the most accurate measurements of grass canopy interception compared to the WWM and WIM, and highlights the leaf contact angle as a key factor in explaining interspecies differences. These findings could enhance the understanding of grass canopy interception and guide the selection of experimental methods.

Soil heavy metal pollution promotes extracellular enzyme production by mediating microbial community structure during vegetation restoration of metallic tailing reservoir.

Vegetation restoration in metallic tailing reservoirs is imperative to restore the post-mining degraded ecosystems. Extracellular enzymes determine microbial resource acquisition in soils, yet the mechanisms controlling the enzyme activity and stoichiometry during vegetation restoration in metallic tailing reservoirs remain elusive. Here, we investigated the variations and drivers of C-, N- and P-acquiring enzymes together with microbial community along a 50-year vegetation restoration chronosequence in the China's largest vanadium titano-magnetite tailing reservoir. We found a parabolic pattern in the enzyme activity and efficiency along the chronosequence, peaking at the middle restoration stage (∼30 years) with approximately six-fold increase relative to the initial 1-year site. The enzyme ratios of C:P and N:P decreased by 33 % and 68 % along the chronosequence, respectively, indicating a higher microbial demand of C and N at the early stage and a higher demand of P at the later stage. Soil nutrients directly determined the enzyme activities and stoichiometry, whereas microbial biomass and community structure regulated the temporal pattern of the enzyme efficiency. Surprisingly, increased heavy metal pollution imposed a positive effect on the enzyme efficiency indirectly by altering microbial community structure. This was evidenced by the increased microbial diversity and the conversion of copiotrophic to oligotrophic and stress-tolerant taxa along the chronosequence. Our findings provide new insights into microbial functioning in soil nutrient dynamics during vegetation restoration under increasing heavy metal pollution.

Numerical Investigation of Funicular Liquid Bridges between Three Spherical Grains in a Bidisperse Particulate System.

Appropriate capillary effects are beneficial for controlling the wet powder performance and agglomerate formation. As water content rises, the funicular regime supplants the pendular regime as the predominant state in wet granular media. The displacement of grains leading to the stretching of funicular liquid bridges until rupture is an interesting and common phenomenon. Utilizing Surface Evolver software (an energy minimization approach), this work develops an efficient and accurate numerical model to describe liquid interactions among three spherical grains. The effects of liquid volume, contact angle, grain size ratio, grain-pair gap, and separation distance on the capillary forces and rupture distances are investigated. Notably, we present a modified closed-form equation for predicting the rupture distance of funicular bridges between three grains, which reflects the coupled effects of the contact angle, grain size, and liquid volume on rupture distance. This present study provides insights for incorporating capillary effects into mechanical models relying on microassembly composed of several grains in bidisperse particulate systems. Additionally, the numerical findings confirm some findings regarding the splitting of funicular bridges.

Supported nano-sized precious metal catalysts for oxidation of catalytic volatile organic compounds.

Volatile organic compounds (VOCs) are common contaminants found as indoor as well as outdoor pollutants, which can induce acute or chronic health hazards to the human physiological system. The catalytic oxidation method is widely considered as one of the effective methods for removing VOCs, and the development of highly effective catalysts is highly urgent for booming this interesting field. This review focuses on the recent progress of VOC oxidation catalyzed by supported nano-sized precious metal catalysts, and discusses the effects of metal composition, supports, size, and morphology on the catalytic activity. In addition, the roles played by both nano-sized precious metals and supports in enhancing the performance of catalytic VOCs are also systematically discussed, which will guide the further development of more advanced VOC catalysts.

Discovery of anti-inflammatory agents from 3, 4-dihydronaphthalene-1(2H)-one derivatives by inhibiting NLRP3 inflammasome activation.

NLRP3 inflammatory vesicles are a polymer of cellular innate immunity composed of a pair of proteins. The continuous activation of NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammatory vesicles induces the occurrence and enhancement of inflammatory response. In this study, a series of 3, 4-dihydronaphthalene-1(2H)-one derivatives (DHNs, 6a-u, 7a-e, 8a-n) were synthesized and characterized by NMR and HRMS. We evaluated the cytotoxicity and anti-inflammatory activity of all compounds in vitro, and selected 7a substituted by 7-Br in A-ring and 2-pyridylaldehyde in C-ring as effective lead compounds. Specifically, 7a can block the assembly and activation of NLRP3 inflammasome by down-regulating the expression of NLPR3 and apoptosis-associated speck-like protein containing a CARD (ASC), and inhibiting the production of reactive oxygen species (ROS) and other inflammatory mediators. In addition, 7a inhibits the phosphorylation of inhibitor kappa B alpha (IκBα) and NF-κB/p65 and the nuclear translocation of p65, thereby inhibiting nuclear factor kappa-B (NF-κB) signaling. Molecular docking analysis confirmed that 7a could reasonably bind the active sites of NLRP3, ASC and p65 proteins. Therefore, 7a is predicted as a potential NLRP3 inflammatory vesicle inhibitor and deserves further research and development.

Strategies to Enhance l-Isoleucine Synthesis by Modifying the Threonine Metabolism Pathway in Escherichia coli.

l-threonine as an important precursor substance of l-isoleucine and improving its accumulation in Escherichia coli became an important idea to construct a chassis strain with high l-isoleucine production. Meanwhile, the effect of l-threonine metabolic pathway disruption in E. coli for the improved production of l-isoleucine remains unrevealed. In the present study, a mutant strain of E. coli was engineered by inactivating specific metabolic pathways (e.g., Δtdh, ΔltaE, and ΔyiaY) that were associated with l-threonine metabolism but unrelated to l-isoleucine synthesis. This was done with the aim to reduce the breakdown of l-threonine and, thereby, increase the production of l-isoleucine. The results obtained demonstrated a 72.3% increment in l-isoleucine production from 4.34 to 7.48 g·L-1 in the mutant strain compared with the original strain, with an unexpected 10.3% increment in bacterial growth as measured at OD600. Transcriptome analysis was also conducted on both the mutant strain NXU102 and the original strain NXU101 in the present study to gain a comprehensive understanding of their physiological attributes. The findings revealed a notable disparity in 1294 genes between the two strains, with 658 genes exhibiting up-regulation and 636 genes displaying down-regulation. The activity of tricarboxylic acid (TCA) cycle-related genes was found to decrease, but oxidative phosphorylation-related genes were highly up-regulated, which explained the increased activity of the mutant strain. For instance, l-lysine catabolism-related genes were found to be up-regulated, which reconfigured the carbon flow into the TCA cycle. The augmentation of acetic acid degradation pathway-related genes assisted in the reduction in acetic acid accumulation that could retard cell growth. Notably, substantial up-regulation of the majority of genes within the aspartate pathway could potentially account for the increased production of l-isoleucine in the present study. In this paper, a chassis strain with an l-isoleucine yield of 7.48 g·L-1 was successfully constructed by cutting off the threonine metabolic pathway. Meanwhile, transcriptomic analysis revealed that the cutting off of the threonine metabolic pathway induced perturbation of genes related to the pathways associated with the synthesis of l-isoleucine, such as the tricarboxylic acid cycle, glycolysis, and aspartic acid pathway.

An improved medium for in vitro studies of female reproduction and oviposition in Schistosoma japonicum.

BACKGROUND: Schistosomiasis is a disease primarily caused by eggs laid by pathogens called schistosomes. Among the schistosome species infecting humans, Schistosoma japonicum possesses the largest fecundity; each adult female produces an average of 3500 eggs per day. The lack of proper culture conditions supporting continuous oviposition in vitro has precluded detailed investigation of mechanisms regulating sexual maturation and egg production in Schistosoma japonicum. METHODS: We optimized in vitro culture conditions by replacing reagents that are part of the classical ABC169 medium. Fast Blue BB staining and 4',6-diamidino-2-phenylindole (DAPI) labeling were applied to observe the sexual development status of the females. In vitro RNA interference (RNAi) technology was used to validate the capability of the modified medium. The detection of male ß-alanyl-tryptamine (BATT) was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Both m-AB169 (1640) and AB169 (1640) media are capable of facilitating the sexual development of paired virgin female S. japonicum, as well as sustaining the mature reproductive organs and egg production of adult S. japonicum for at least 22 days in vitro. M-AB169 (1640) provided a more stable condition for supporting the sexual maturity of female S. japonicum, as evidenced by the consistent initiation of egg production compared with AB169 (1640). Through a comparative analysis of S. japonicum and S. mansoni in diverse media, we demonstrated that these closely related species display distinct demands for their sexual development and egg production, suggesting a potential influence of nutritional factors on the observed variations in host ranges among different schistosome species. Importantly, we successfully identified the presence of the pheromone ß-alanyl-tryptamine (BATT) in S. japonicum, previously identified in S. mansoni, highlighting its conserved role in schistosome reproductive development. Through the employment of double-stranded RNA (dsRNA) treatment to silence two genes that are involved in either the male (gli1, glioma-associated oncogene homolog 1) or female (vf1, vitellogenic factor 1) side in male-induced female reproductive development of S. mansoni, we confirmed that the combination of m-AB169 (1640) and RNAi technology has the capacity to facilitate in vitro studies of S. japonicum's reproductive and oviposition processes. CONCLUSIONS: We developed a novel medium, m-AB169 (1640), that not only maintains the mature reproductive organs and continuous oviposition of adult female Schistosoma japonicum for up to 22 days but also supports the reproductive development and subsequent egg-laying of virgin females after pairing with male worms. This study provides a valuable in vitro platform for functional studies of the mechanisms underlying the fascinating biology of the female sexual development and egg production of S. japonicum, which may accelerate the development of new strategies targeting schistosome egg production.

Enhancing regenerative medicine: the crucial role of stem cell therapy.

Stem cells offer new therapeutic avenues for the repair and replacement of damaged tissues and organs owing to their self-renewal and multipotent differentiation capabilities. In this paper, we conduct a systematic review of the characteristics of various types of stem cells and offer insights into their potential applications in both cellular and cell-free therapies. In addition, we provide a comprehensive summary of the technical routes of stem cell therapy and discuss in detail current challenges, including safety issues and differentiation control. Although some issues remain, stem cell therapy demonstrates excellent potential in the field of regenerative medicine and provides novel tactics and methodologies for managing a wider spectrum of illnesses and traumas.

Schistosome Infection Impacts Hematopoiesis.

Helminth infections are common in animals. However, the impact of a helminth infection on the function of hematopoietic stem cells (HSCs) and other hematopoietic cells has not been comprehensively defined. In this article, we describe the hematopoietic response to infection of mice with Schistosoma mansoni, a parasitic flatworm that causes schistosomiasis. We analyzed the frequency or number of hematopoietic cell types in the bone marrow, spleen, liver, thymus, and blood and observed multiple hematopoietic changes caused by infection. Schistosome infection impaired bone marrow HSC function after serial transplantation. Functional HSCs were present in the infected liver. Infection blocked bone marrow erythropoiesis and augmented spleen erythropoiesis, observations consistent with the anemia and splenomegaly prevalent in schistosomiasis patients. This work defines the hematopoietic response to schistosomiasis, a debilitating disease afflicting more than 200 million people, and identifies impairments in HSC function and erythropoiesis.

Dynamic profiles of lncRNAs reveal a functional natural antisense RNA that regulates the development of Schistosoma japonicum.

Schistosomes are flatworm parasites that undergo a complex life cycle involving two hosts. The regulation of the parasite's developmental processes relies on both coding RNAs and non-coding RNAs. However, the roles of non-coding RNAs, including long non-coding RNAs (lncRNAs) in schistosomes remain largely unexplored. Here we conduct advanced RNA sequencing on male and female S. japonicum during their pairing and reproductive development, resulting in the identification of nearly 8,000 lncRNAs. This extensive dataset enables us to construct a comprehensive co-expression network of lncRNAs and mRNAs, shedding light on their interactions during the crucial reproductive stages within the mammalian host. Importantly, we have also revealed a specific lncRNA, LNC3385, which appears to play a critical role in the survival and reproduction of the parasite. These findings not only enhance our understanding of the dynamic nature of lncRNAs during the reproductive phase of schistosomes but also highlight LNC3385 as a potential therapeutic target for combating schistosomiasis.

Synergistic action of cavity and catalytic sites in etched Pd-Cu2O octahedra to augment the peroxidase-like activity of Cu2O nanoparticles for the colorimetric detection of isoniazid and ascorbic acid.

Despite the widespread use of nanozyme-based colorimetric assays in biosensing, challenges such as limited catalytic efficiency, inadequate sensitivity to analytes, and insufficient understanding of the structure-activity relationship still persist. Overcoming these hurdles by enhancing the inherent enzyme-like performance of nanozymes using the unique attributes of nanomaterials is still a significant obstacle. Here, we designed and constructed Pd-Cu2O nanocages (Pd-Cu2O NCs) by selectively etching the vertices of the copper octahedra to enhance the peroxidase-like (POD-like) activity of Cu2O nanoparticles. The improved catalytic activity of Pd-Cu2O NCs was attributed to their high specific surface area and abundant catalytic sites. Mechanistic studies revealed that reactive oxygen species (ROS) intermediates (•OH) were generated through the decomposition of H2O2, resulting in POD-like activity of the Pd-Cu2O NCs. The designed Pd-Cu2O NCs can oxidize 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, producing a blue oxidation product (oxTMB). The oxidation reaction was inhibited and led to a significant bleaching of the blue color in the presence of reducing substances isoniazid (INH) and ascorbic acid (AA). Based on these principles, we developed a colorimetric sensing platform for the detection of INH and AA, exhibiting good sensitivity and stability. This work provided a straightforward approach to the structural engineering of nanomaterials and the enhancement of enzyme-mimicking properties.

Optimization of catalytic wet air oxidation process in microchannel reactor for TBBS wastewater treatment.

Catalytic wet air oxidation (CWAO) process is employed for the treatment of N-tert-butyl-2-benzothiazolesulfenamide (TBBS) wastewater in a microchannel reactor that enables continuous operation of the reaction and allows for thorough mixing of oxygen and pollutants. To achieve the optimal process performance, four key parameters of pressure, temperature, time, and the mass ratio of input oxygen to wastewater COD are optimized using both response surface methodology (RSM) and backpropagation artificial neural network (BP-ANN). According to the correlation coefficients of model results and experimental data, BP-ANN performs better than RSM in simulation and prediction. The analysis of variance in RSM shows that all parameters are significant for the obtained quadratic model, but their interactions with each other are not significant. Connection weights algorithm is used to determine the relative importance of these parameters for the process efficiency, and it is demonstrated that temperature is the most influential parameter with a relative importance of 35.61%, followed by pressure (29.74%), time (19.53%) and ROC (15.12%).

CT-based deep learning model: a novel approach to the preoperative staging in patients with peritoneal metastasis.

Peritoneal metastasis (PM) is a frequent manifestation of advanced abdominal malignancies. Accurately assessing the extent of PM before surgery is essential for patients to receive optimal treatment. Therefore, we propose to construct a deep learning (DL) model based on enhanced computed tomography (CT) images to stage PM preoperatively in patients. All 168 patients with PM underwent contrast-enhanced abdominal CT before either open surgery or laparoscopic exploration, and peritoneal cancer index (PCI) was used to evaluate patients during the surgical procedure. DL features were extracted from portal venous-phase abdominal CT scans and subjected to feature selection using the Spearman correlation coefficient and LASSO. The performance of models for preoperative staging was assessed in the validation cohort and compared against models based on clinical and radiomics (Rad) signature. The DenseNet121-SVM model demonstrated strong patient discrimination in both the training and validation cohorts, achieving AUC was 0.996 in training and 0.951 validation cohort, which were both higher than those of the Clinic model and Rad model. Decision curve analysis (DCA) showed that patients could potentially benefit more from treatment using the DL-SVM model, and calibration curves demonstrated good agreement with actual outcomes. The DL model based on portal venous-phase abdominal CT accurately predicts the extent of PM in patients before surgery, which can help maximize the benefits of treatment and optimize the patient's treatment plan.

Analysis of sputum microbial flora in chronic obstructive pulmonary disease patients with different phenotypes during acute exacerbations.

BACKGROUND: Increasing studies have shown that the imbalance of the respiratory microbial flora is related to the occurrence of COPD, the severity and frequency of exacerbations and mortality.However, it remains unclear how the sputum microbial flora differs during exacerbations in COPD patients manifesting emphysema phenotype, chronic bronchitis with emphysema phenotype and asthma-COPD overlap phenotype. METHODS: Sputum samples were obtained from 29 COPD patients experiencing acute exacerbations who had not received antibiotics or systemic corticosteroids within the past four weeks.Patients were divided into three groups;emphysema phenotype(E);chronic bronchitis with emphysema phenotype(B+E) and asthma-COPD overlap phenotype(ACO).We utilized metagenomic Next Generation Sequencing (mNGS) technology to analyze the sputum microbial flora in COPD patients with different phenotypes during exacerbations. RESULTS: There was no significant difference in alpha diversity and beta diversity among three groups.The microbial flora composition was similar in all three groups during exacerbations except for a significant increase in Streptococcus mitis in ACO.Through network analysis,we found Candidatus Saccharibacteria oral taxon TM7x and Fusobacterium necrophorum were the core nodes of the co-occurrence network in ACO and E respectively.They were positively correlated with some species and play a synergistic role.In B+E,Haemophilus pittmaniae and Klebsiella pneumoniae had a synergistic effect.Besides,some species among the three groups play a synergistic or antagonistic role.Through Spearman analysis,we found the relative abundance of Streptococcus mitis was negatively correlated with the number of hospitalizations in the past year(r = -0.410,P = 0.027).We also observed that the relative abundance of Prevotella and Prevotella melaninogenica was negatively correlated with age(r = -0.534,P = 0.003;r = -0.567,P = 0.001),while the relative abundance of Streptococcus oralis and Actinomyces odontolyticus was positively correlated with age(r = 0.570,P = 0.001;r = 0.480,P = 0.008).In addition,the relative abundance of Prevotella melaninogenica was negatively correlated with peripheral blood neutrophil ratio and neutrophil to lymphocyte ratio(r = -0.479,P = 0.009;r = -0.555,P = 0.002),while the relative abundance of Streptococcus sanguinis was positively correlated with peripheral blood neutrophil ratio and neutrophil to lymphocyte ratio (r = 0.450,P = 0.014;r = 0.501,P = 0.006).There was also a significant positive correlation between Oribacterium and blood eosinophil counts(r = 0.491,P = 0.007). CONCLUSION: Overall,we analyzed the sputum microbiota of COPD patients with different phenotypes and its relationship with clinical indicators, and explored the relationships between microbiota and inflammation in COPD.We hope to alter the prognosis of patients by inhibiting specific bacterial taxa related to inflammation and using guide individualized treatment in the future research.

Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2.

Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases and is considered as the most common type of cancer. DLX4 was originally identified as a ß-globin gene suppressor in red blood cells, which plays critical roles in several types of cancers. However, the role and related mechanism of DLX4 in NSCLC are still unclear. The study aimed to uncover the expression of DLX4 in human NSCLC cells and tissues, reveal its possible role in NSCLC, and investigate the underlying mechanisms. Immunoblot and TCGA database were used to detect the expression of DLX4 in human NSCLC cells and tissues. CCK-8, colony formation, and FCM assays were conducted to detect the effects of DLX4 on the viability and cell cycle of NCI-H2170 and A549 cells. Immunoblot assays were further performed to investigate the possible mechanism underlying DLX4 affecting the growth of NSCLC. We revealed that knockdown of DLX4 inhibited NSCLC cell proliferation. We further revealed that DLX4 knockdown induced the NSCLC cell cycle arrest. Our results further showed that downregulation of DLX4 suppressed YB-1 expression, which further suppressed CKS2 expression, thereby suppressing tumor growth of NSCLC. In conclusion, DLX4 has the potential to serve as a promising drug for NSCLC treatment.