Regulating Gelation and Luminescence Behaviors of Single Pyridine-Functionalized Cyanostilbene via Metal Ions.

Luminescent metal-organic gels (LMOGs) have gained much attention due to their crucial role in visual recognition and information encryption. However, it is still a challenge to simplify the design of ligands and enrich the stimuli responses in LMOGs simultaneously. Herein, although a single pyridine ligand cannot form gel alone, after coordination with metal ions, two kinds of LMOGs have been obtained with pyridine-metal complexes, where metal ions can act as cogelators and regulate luminescence of the pyridine-functionalized cyanostilbene ligand at the same time. The effects of metal types on the fluorescence emission color, the fluorescence quantum yield, the fibril network, and the assembly mode of the gel have been investigated systematically. In addition, two competitive ligands were used to regulate the fluorescence and phase transition of the gel. Finally, the logic gates and the information encryption and decryption have been successfully constructed. This kind of material is expected to be applied to fluorescence display, advanced information encryption, high-tech anticounterfeit, and so forth.

CD39hi identifies an exhausted tumor-reactive CD8+ T cell population associated with tumor progression in human gastric cancer.

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.

A quadruple-stimuli responsive supramolecular hydrogel constructed from a poly(acrylic acid) derivative and ß-cyclodextrin dimer.

The fabrication of stimulus-responsive supramolecular hydrogels as smart materials has attracted much attention in recent years. However, the multi-stimuli responsiveness often requires complicated chemical synthesis and rational molecular design. Herein, a quadruple-stimuli responsive supramolecular hydrogel was designed through the host-guest interaction between a ß-CD dimer and a methoxy-azobenzene (mAzo) and ferrocene (Fc) grafted poly(acrylic acid) derivative, as well as through the electrostatic interaction of negatively charged carboxyl side groups. Owing to the dynamic properties of the host-guest and electrostatic interactions, reversible sol-gel transition can be triggered by various stimuli, including temperature, light irradiations, pH changes and chemical redox reagents. As a result, the release of rhodamine B loaded in the hydrogel can be accelerated by green light irradiation, oxidizing agents and low pH, demonstrating potential applications in biomedical materials.

The different brain areas occupied for integrating information of hierarchical linguistic units: a study based on EEG and TMS.

Human language units are hierarchical, and reading acquisition involves integrating multisensory information (typically from auditory and visual modalities) to access meaning. However, it is unclear how the brain processes and integrates language information at different linguistic units (words, phrases, and sentences) provided simultaneously in auditory and visual modalities. To address the issue, we presented participants with sequences of short Chinese sentences through auditory, visual, or combined audio-visual modalities while electroencephalographic responses were recorded. With a frequency tagging approach, we analyzed the neural representations of basic linguistic units (i.e. characters/monosyllabic words) and higher-level linguistic structures (i.e. phrases and sentences) across the 3 modalities separately. We found that audio-visual integration occurs in all linguistic units, and the brain areas involved in the integration varied across different linguistic levels. In particular, the integration of sentences activated the local left prefrontal area. Therefore, we used continuous theta-burst stimulation to verify that the left prefrontal cortex plays a vital role in the audio-visual integration of sentence information. Our findings suggest the advantage of bimodal language comprehension at hierarchical stages in language-related information processing and provide evidence for the causal role of the left prefrontal regions in processing information of audio-visual sentences.

Social support, family resilience and psychological resilience among maintenance hemodialysis patients: a longitudinal study.

BACKGROUND: Psychological distress is common in maintenance hemodialysis patients, and high psychological resilience can promote psychological well-being. The current research focuses on psychological resilience protective factors such as family resilience and social support. However, the trajectories of psychological resilience, family resilience, and social support over time and their longitudinal relationships in maintenance hemodialysis patients have not been fully explored yet. Therefore, this study aims to explore the longitudinal relationship between these factors. METHODS: Patients who received regular hemodialysis treatment for more than three months at dialysis centers of three tertiary hospitals in Zhejiang, China, were recruited from September to December 2020. A total of 252 patients who met the inclusion and exclusion criteria completed three follow-up surveys, including social support, family resilience, and psychological resilience assessments. A repeated measures ANOVA was used to explore differences in their respective scores at different time points. The cross-lagged analysis was performed in AMOS using the maximum likelihood method to examine the the reciprocal predictive relationships between these factors. RESULTS: Social support and psychological resilience remained relatively stable over time, whereas family resilience indicated a little increasing trend. According to the cross-lagged analysis, higher T1 social support predicted higher family resilience at T2 [ß = 0.123, 95% CI (0.026-0.244)]. Further, the effects of T2 social support to T3 family resilience [ß = 0.194, 95%CI (0.039-0.335)] and psychological resilience [ß = 0.205, 95%CI (0.049-0.354)] were significant. Finally, the effects of T2 family resilience to T3 social support [ß = 0.122, 95%CI (0.010-0.225)] and psychological resilience [ß = 0.244, 95%CI (0.119-0.359)] were also significant. CONCLUSIONS: The study showed that the directionality of the relationship appears to be from social support or family resilience to patients' psychological resilience but not vice versa. This finding reminds healthcare professionals to emphasize the vital role of social and family resources in providing appropriate support and interventions for maintenance hemodialysis patients to promote psychological resilience and mental health development.

Identification of common sequence motifs shared exclusively among selectively packed exosomal pathogenic microRNAs during rickettsial infections.

We previously reported that microRNA (miR)23a and miR30b are selectively sorted into exosomes derived from rickettsia-infected endothelial cells (R-ECExos). Yet, the mechanism remains unknown. Cases of spotted fever rickettsioses have been increasing, and infections with these bacteria cause life-threatening diseases by targeting brain and lung tissues. Therefore, the goal of the present study is to further dissect the molecular mechanism underlying R-ECExos-induced barrier dysfunction of normal recipient microvascular endothelial cells (MECs), depending on their exosomal RNA cargos. Infected ticks transmit the rickettsiae to human hosts following a bite and injections of the bacteria into the skin. In the present study, we demonstrate that treatment with R-ECExos, which were derived from spotted fever group R parkeri infected human dermal MECs, induced disruptions of the paracellular adherens junctional protein VE-cadherin, and breached the paracellular barrier function in recipient pulmonary MECs (PMECs) in an exosomal RNA-dependent manner. We did not detect different levels of miRs in parent dermal MECs following rickettsial infections. However, we demonstrated that the microvasculopathy-relevant miR23a-27a-24 cluster and miR30b are selectively enriched in R-ECExos. Bioinformatic analysis revealed that common sequence motifs are shared exclusively among the exosomal, selectively-enriched miR23a cluster and miR30b at different levels. Taken together, these data warrant further functional identification and characterization of a monopartition, bipartition, or tripartition among ACA, UCA, and CAG motifs that guide recognition of microvasculopathy-relevant miR23a-27a-24 and miR30b, and subsequently results in their selective enrichments in R-ECExos.

Combined inhibition of surface CD51 and γ-secretase-mediated CD51 cleavage improves therapeutic efficacy in experimental metastatic hepatocellular carcinoma.

BACKGROUND & AIMS: Integrin αv (ITGAV, CD51) is regarded as a key component in multiple stages of tumor progression. However, the clinical failure of cilengitide, a specific inhibitor targeting surface CD51, suggests the importance of yet-unknown mechanisms by which CD51 promotes tumor progression. METHODS: In this study, we used several hepatocellular carcinoma (HCC) cell lines and murine hepatoma cell lines. To investigate the role of CD51 on HCC progression, we used a 3D invasion assay and in vivo bioluminescence imaging. We used periostin-knockout transgenic mice to uncover the role of the tumor microenvironment on CD51 cleavage. Moreover, we used several clinically relevant HCC models, including patient-derived organoids and patient-derived xenografts, to evaluate the therapeutic efficacy of cilengitide in combination with the γ-secretase inhibitor LY3039478. RESULTS: We found that CD51 could undergo transmembrane cleavage by γ-secretase to produce a functional intracellular domain (CD51-ICD). The cleaved CD51-ICD facilitated HCC invasion and metastasis by promoting the transcription of oxidative phosphorylation-related genes. Furthermore, we identified cancer-associated fibroblast-derived periostin as the major driver of CD51 cleavage. Lastly, we showed that cilengitide-based therapy led to a dramatic therapeutic effect when supplemented with LY3039478 in both patient-derived organoid and xenograft models. CONCLUSIONS: In summary, we revealed previously unrecognized mechanisms by which CD51 is involved in HCC progression and uncovered the underlying cause of cilengitide treatment failure, as well as providing evidence supporting the translational prospects of combined CD51-targeted therapy in the clinic. IMPACT AND IMPLICATIONS: Integrin αv (CD51) is a widely recognized pro-tumoral molecule that plays a crucial role in various stages of tumor progression, making it a promising therapeutic target. However, despite early promising results, cilengitide, a specific antagonist of CD51, failed in a phase III clinical trial. This prompted further investigation into the underlying mechanisms of CD51's effects. This study reveals that the γ-secretase complex directly cleaves CD51 to produce an intracellular domain (CD51-ICD), which functions as a pro-tumoral transcriptional regulator and can bypass the inhibitory effects of cilengitide by entering the nucleus. Furthermore, the localization of CD51 in the nucleus is significantly associated with the prognosis of patients with HCC. These findings provide a theoretical basis for re-evaluating cilengitide in clinical settings and highlight the importance of identifying a more precise patient subpopulation for future clinical trials targeting CD51.

Genome-wide identification of SrbHLH transcription factors highlights its potential role in rebaudioside A (RA) biosynthesis in Stevia rebaudiana.

Stevia rebaudiana Bertoni is a valuable medicinal plant and an essential source of natural sweetener, steviol glycosides (SGs), with rebaudioside A (RA) being one of the main components of SGs. bHLH transcription factors play a crucial role in plant development and secondary metabolism. In this study, 159 SrbHLH genes were identified from the S. rebaudiana genome, and each gene was named based on its chromosome location. The SrbHLH proteins were then clustered into 18 subfamilies through phylogenetic analysis. The analysis of conserved motifs and gene structure further supported the classification of the SrbHLH family. Chromosomal location and gene duplication events of SrbHLH genes were also studied. Moreover, based on the RNA-Seq data of different tissues of S. rebaudiana, 28 SrbHLHs were co-expressed with structural genes involved in RA biosynthesis. The expression pattern of candidate SrbHLH genes were confirmed by qPCR. Finally, dual luciferase reporter assays (DLAs) and subcellular localization analysis verified SrbHLH22, SrbHLH111, SrbHLH126, SrbHLH142, and SrbHLH152 are critical regulators of RA biosynthesis. This study provides new insights into the function of SrbHLHs in regulating SGs biosynthesis and lays the foundation for future applications of SrbHLH genes in molecular breeding of S. rebaudiana.

Recent Progress in Metal Phosphorous Chalcogenides: Potential High-Performance Electrocatalysts.

Since the discovery of graphene, research on the family of 2D materials has been a thriving field. Metal phosphorous chalcogenides (MPX3 ) have attracted renewed attention due to their distinctive physical and chemical properties. The advantages of MPX3 , such as tunable layered structures, unique electronic properties, thermodynamically appropriate band alignments and abundant catalytic active sites on the surface, make MPX3 material great potential in electrocatalysis. In this review, the applications of MPX3 electrocatalysts in recent years, including hydrogen evolution reaction, oxygen evolution reaction, and oxygen reduction reaction, are summarized. Structural regulation, chemical doping and multi-material composite that are often effective and practical research methods to further optimize the catalytic properties of these materials, are introduced. Finally, the challenges and opportunities for electrocatalytic applications of MPX3 materials are discussed. This report aims to advance future efforts to develop MPX3 and related materials for electrocatalysis.

Loss of YAP1 C-terminus expression as an ancillary marker for metaplastic thymoma: a potential pitfall in detecting YAP1::MAML2 gene rearrangement.

AIMS: Metaplastic thymoma is a rare thymic tumour characterized by Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) gene fusions resulting from an intrachromosomal inversion of chromosome 11. Immunohistochemistry with an antibody directed against the C-terminus of YAP1 has shown loss of expression in YAP1-rearranged vascular neoplasms, poromas, and porocarcinomas. This study aimed to validate an anti-YAP1 C-terminal antibody as an ancillary immunohistochemical marker for the diagnosis of metaplastic thymoma. MATERIALS AND METHODS: Ten metaplastic thymomas were selected for the current study. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed to detect YAP1::MAML2 fusions. We then performed immunohistochemistry to detect YAP1 C-terminus expression in 10 metaplastic thymomas, 50 conventional thymomas (10 each of type A thymoma, type AB thymoma, type B1 thymoma, type B2 thymoma, and type B3 thymoma) and seven thymic carcinomas. RESULTS: All 10 cases showed narrow split signals with a distance of nearly two signal diameters and sometimes had false-negative results in YAP1 and MAML2 break-apart FISH (BA-FISH). Abnormal colocalized signals of the YAP1::MAML2 fusion were observed in all 10 cases using fusion FISH (F-FISH) assays. Eight of 10 cases with adequate nucleic acids were successfully sequenced and all showed YAP1::MAML2 fusions; in two cases the fusions were detected by both DNA and RNA sequencing and in six cases by RNA sequencing only. YAP1::MAML2 fusion transcripts were identified in four cases by RT-PCR. Metaplastic thymoma showed loss of YAP1 C-terminus expression in all 10 (100%) cases. All other thymic neoplasms showed retained YAP1 C-terminus expression. CONCLUSION: YAP1 C-terminus immunohistochemistry is a highly sensitive and specific ancillary marker that distinguishes metaplastic thymoma from its mimics. BA-FISH assays could not effectively detect YAP1::MAML2 fusions due to the proximity of the two genes. Loss of YAP1 C-terminus expression is a reliable surrogate for the detection of YAP1::MAML2 fusions in metaplastic thymoma.

Balancing Compatibility and Gelability for High-Performance Cholesteric Liquid Crystalline Physical Gels.

Liquid crystalline physical gels (LCPGs) have attracted increasing interest because of their mechanical properties and stimulus-response behaviors. However, due to their gelator properties such as thermal stability, gelation capability, and compatibility in liquid crystals, development of LCPGs with high performances still remains a huge challenging task. Herein, four novel gelators ((l)-PH, (d)-PH, (l)-P2H, and (d)-P2H) based on 1,4-benzenedicarboxamide phenylalanine derivatives containing one or two ethylene glycol groups have been designed and synthesized. It is found that the ethylene glycol group plays a significant role in improving the compatibility between the gelator and the liquid crystal. All of the prepared compounds can form stable LCPGs in P0616A. In particular, the storage modulus of LCPG with 9.0 wt % of (l)-PH with one ethylene glycol unit is higher than 106 Pa, which is similar to SmC gels and advantageous over previously reported nematic LCPGs. Furthermore, the prepared gels display a strong Cotton effect with hand-preferred twisted fiber networks and the self-assembled aggregates of (l)-PH can induce P0616A to form a cholesteric fingerprint structure. Thus, these low molecular weight gelators provide a strategy to construct high-performance cholesteric LCPGs for the realization of LC device applications.

Extending Conjugation of Linear Cyanostilbene Derivatives via a Pyridine Moiety for Multi-Stimuli-Responsive Fluorescence Organogels.

In the design of effective gelators with aggregation-induced emission behavior, amide and cholesterol moieties are generally used to provide multiple driving forces for gelation. In this work, a series of linear cyanostilbene gelators with a pyridine moiety and different lengths of the alkoxyl group, i.e., CSpy-Cn, have been synthesized through nucleophilic substitution and Knoevenagel reaction. The direct connection of pyridine extends the conjugation of the cyanostilbene moiety, while the alkoxyl group can regulate the solubility of the compounds so that the compounds can serve as gelators for common solvents such as acetonitrile, dimethyl sulfoxide, and ethanol at ultra-low concentrations. At the same time, the cyanostilbene group makes the compounds undergo photoisomerization and emit fluorescence under UV light, while the pyridine group can serve as an acid-base responsive group due to easy protonation. The gels can respond to temperature, light, and organic acid/base. The fluorescence intensity and color can reversibly change during the gel-sol transitions. Finally, a thin film based on the CSpy-C8 xerogel has been prepared and utilized as a multi-stimuli-responsive fluorescence display for information storage and anti-counterfeiting.

Roles of the peroxisome proliferator-activated receptors (PPARs) in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease phenotypes which start with simple steatosis and lipid accumulation in the hepatocytes - a typical histological lesions characteristic. It may progress to non-alcoholic steatohepatitis (NASH) that is characterized by hepatic inflammation and/or fibrosis and subsequent onset of NAFLD-related cirrhosis and hepatocellular carcinoma (HCC). Due to the central role of the liver in metabolism, NAFLD is regarded as a result of and contribution to the metabolic abnormalities seen in the metabolic syndrome. Peroxisome proliferator-activated receptors (PPARs) has three subtypes, which govern the expression of genes responsible for energy metabolism, cellular development, inflammation, and differentiation. The agonists of PPARα, such as fenofibrate and clofibrate, have been used as lipid-lowering drugs in clinical practice. Thiazolidinediones (TZDs) - ligands of PPARγ, such as rosiglitazone and pioglitazone, are also used in the treatment of type 2 diabetes (T2D) with insulin resistance (IR). Increasing evidence suggests that PPARß/δ agonists have potential therapeutic effects in improving insulin sensitivity and lipid metabolism disorders. In addition, PPARs ligands have been considered as potential therapeutic drugs for hypertension, atherosclerosis (AS) or diabetic nephropathy. Their crucial biological roles dictate the significance of PPARs-targeting in medical research and drug discovery. Here, it reviews the biological activities, ligand selectivity and biological functions of the PPARs family, and discusses the relationship between PPARs and the pathogenesis of NAFLD and metabolic syndrome. This will open new possibilities for PPARs application in medicine, and provide a new idea for the treatment of fatty liver and related diseases.

Techniques improving electrical cardioversion success for patients with atrial fibrillation: a systematic review and meta-analysis.

AIMS: Electrical cardioversion is commonly used to restore sinus rhythm in patients with atrial fibrillation (AF), but procedural technique and clinical success vary. We sought to identify techniques associated with electrical cardioversion success for AF patients. METHODS AND RESULTS: We searched MEDLINE, EMBASE, CENTRAL, and the grey literature from inception to October 2022. We abstracted data on initial and cumulative cardioversion success. We pooled data using random-effects models. From 15 207 citations, we identified 45 randomized trials and 16 observational studies. In randomized trials, biphasic when compared with monophasic waveforms resulted in higher rates of initial [16 trials, risk ratio (RR) 1.71, 95% CI 1.29-2.28] and cumulative success (18 trials, RR 1.10, 95% CI 1.04-1.16). Fixed, high-energy (≥200 J) shocks when compared with escalating energy resulted in a higher rate of initial success (four trials, RR 1.62, 95% CI 1.33-1.98). Manual pressure when compared with no pressure resulted in higher rates of initial (two trials, RR 2.19, 95% CI 1.21-3.95) and cumulative success (two trials, RR 1.19, 95% CI 1.06-1.34). Cardioversion success did not differ significantly for other interventions, including: antero-apical/lateral vs. antero-posterior positioned pads (initial: 11 trials, RR 1.16, 95% CI 0.97-1.39; cumulative: 14 trials, RR 1.01, 95% CI 0.96-1.06); rectilinear/pulsed biphasic vs. biphasic truncated exponential waveform (initial: four trials, RR 1.11, 95% CI 0.91-1.34; cumulative: four trials, RR 0.98, 95% CI 0.89-1.08) and cathodal vs. anodal configuration (cumulative: two trials, RR 0.99, 95% CI 0.92-1.07). CONCLUSIONS: Biphasic waveforms, high-energy shocks, and manual pressure increase the success of electrical cardioversion for AF. Other interventions, especially pad positioning, require further study.

Two-Color Cholesteric Liquid Crystalline Gels for Reversible Writing and Erasing Information Encryption.

Bright structural color derived from the unique helical superstructure of cholesteric liquid crystals (CLCs) has attracted much attention. In addition, fluorescence color is an intrinsic emission upon excitation, which can be observed often under UV light. However, it is a challenge to combine the fluorescence and structural colors to construct a self-supporting system at the same time. In this work, a photoresponsive cyanostilbene-based gelator (CSpy-C10) is synthesized, which emits blue fluorescence in LC. CSpy-C10 can gel LCs and further construct thermo-/photoresponsive CLC physical gels. The structural color of the CLCs, fluorescence, and mechanical properties of the gels can be independently regulated due to the separation of the chiral unit and photoresponsive unit with aggregation-induced emission behavior. Finally, the reversible information encryption including writing and erasing based on the changes in fluorescence are explored. This kind of two-color material can be applied in the fields ranging from information encryption, fluorescent display to high-tech anticounterfeiting.

Vacuum sealing drainage to treat Fournier's gangrene.

BACKGROUND: Vacuum sealing drainage (VSD) is widely applied in complex wound repair. We aimed to compare traditional debridement and drainage and VSD in treating Fournier's gangrene (FG). METHODS: Data of patients surgically treated for FG were retrospectively analyzed. RESULTS: Of the 36 patients (men: 31, women: 5; mean age: 53.5 ± 11.3 [range: 28-74] years) included in the study, no patients died. Between-group differences regarding sex, age, BMI, time from first debridement to wound healing, number of debridements, FGSI, and shock were not statistically significant (P > 0.05). However, lesion diameter, colostomy, VAS score, dressing changes, analgesic use, length of hospital stay, and wound reconstruction method (χ2 = 5.43, P = 0.04) exhibited statistically significant differences. Tension-relieving sutures (6 vs. 21) and flap transfer (4 vs. 2) were applied in Groups I and II, respectively. CONCLUSION: VSD can reduce postoperative dressing changes and analgesic use, and shrunk the wound area, thereby reducing flap transfer in wound reconstruction.

Progress on lysosomal PPT1-mediated regulation of cellular homeostasis and pathogenesis.

Palmitoyl protein thioesterase 1(PPT1) is a lysosomal enzyme that catalyzes the protein depalmitoylation. It is considered to play a crucial role in regulating lysosomes, mitochondria and lipid metabolism. PPT1 has been reported to play an important role in the occurrence and progression of diseases, such as neurological diseases and cancers. However, the regulatory mechanisms remain unknown. In this review, we summarize the progress of PPT1 function and mechanisms in neurological disorders and cancers, which will provide as reference and guidance for exploring the regulatory mechanisms of PPT1 and developing new drugs for treating related diseases in the future.

[Correlation between rhizosphere environment and content of medicinal components of Arnebia euchroma].

This study aimed to explore the correlation between rhizosphere soil microorganisms of wild Arnebia euchroma and the content of medicinal components to provide guidance for the selection of the ecological planting base. The total DNA of rhizosphere soil microorganisms of wild A. euchroma was extracted, and the microbial community structure of rhizosphere soil microorganisms was analyzed by IlluminaMiseq high-throughput sequencing technology. The content of total hydroxynaphthoquinone pigment and ß,ß'-dimethylacrylalkannin in medicinal materials was determined by high-performance liquid chromatography(HPLC). The physicochemical pro-perties of rhizosphere soil of wild A. euchroma in main producing areas were determined, and the correlation of soil microbial abundance with index component content and soil physicochemical properties was analyzed by SPSS software. The results showed that the species composition of rhizosphere fungi and bacteria in A. euchroma from different habitats was similar at the phylum and genus levels, but their relative abundance, richness index(Chao1), and community diversity(Simpson) index were different. Correlation analysis showed that the content of available phosphorus in soil was positively correlated with the content of total hydroxynaphthoquinone pigment and ß,ß'-dimethylacrylalkannin, and the abundance of five fungal genera such as Solicoccozyma and six bacterial genera such as Pseudo-nocardia and Bradyrhizobium was positively correlated with the content of medicinal components in medicinal materials. The abundance of Bradyrhizobium was significantly positively correlated with the content of ß,ß'-dimethylacrylalkanin. The abundance of fungi such as Archaeorhizomyces was significantly positively correlated with the content of available phosphorus in rhizosphere soil, and Bradyrhizobium was significantly negatively correlated with soil pH. Therefore, the abundance of fungi and bacteria in the rhizosphere of A. euchroma has a certain correlation with the medicinal components and the physicochemical properties of the rhizosphere soil, which can provide a scientific basis for the selection of ecological planting bases in the later stage.

ASSOCIATION OF ORAL MICROBIOTA AND PERIODONTAL DISEASE WITH LUNG CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: Evidence of oral microbiota perturbations has been accumulated for lung cancers. This review focused on the oral microbiota alterations in population suffering from lung cancer. In addition, we also discussed conflicting data about the association between oral microbiota dysbiosis and risk of lung cancer. METHODS: A systematic search was conducted in Medline, Embase, PubMed, and Cochrane Library databases. The studies evaluated diversity and abundance of oral microbes in healthy and lung cancer individuals as well as association of periodontal disease and pathogens with lung cancer. Of 3559 studies, 28 included studies were performed in qualitative analysis, and 25 studies were used in meta-analyses for quantitative assessment. Heterogeneity was analyzed by using I² and chi-squared Q test statistics. Statistical analyses were performed by using the RevMan 5.4 software. RESULTS: Compared with the control, lung cancer patients had lower alpha diversity (Shannon: SMD = -0.54; 95% CI, -0.90 to -0.19; P < .01, I2 = 71%). In nested case-control studies, individuals with decreased alpha diversity tended to have an increased risk of lung cancer (observed species: HR = 0.90; 95% CI, 0.85-0.96; P < .01, I2 = 0%; Shannon: HR = 0.89; 95% CI, 0.83-0.95; P < .01, I2 = 0%). Overall, no strong evidence of association of relative abundance with specific oral microbes with lung cancers was found because of inconsistent data. No associations were found between periodontal pathogens and lung cancer risk (red complex: HR = 1.12, 95% CI: 0.42-3.02, P = .82, I2 = 62%; orange complex: HR =1.77, 95% CI: 0.78-3.98, P = .17, I2 = 36%), expect for Fusobacterium nucleatum (HR = 2.27, 95% CI: 1.13-4.58, P = .02, I2 = 0%). The positive association of periodontal disease with lung cancer risk was found (HR = 1.58, 95% CI: 1.25-2.00, P < .001, I2= 0%) with increase of periodontal diseases severity (HR = 2.39, 95% CI: 1.57-3.66, P < .001, I2 = 0%). However, such association was not found in never-smoker participants (HR = 1.00, 95% CI: 0.76-1.31, P = .37, I2= 7%). CONCLUSIONS: Lower alpha diversity of oral microbiome may be associated with a greater risk of lung cancer and might serve as a predictive signal of lung cancer risk. There was no strong evidence of relative abundance of oral microbial taxa and periodontal pathogens in lung cancer patients. Fusobacterium nucleatum might be a potential microbial candidate of biomarkers in lung cancer. Periodontal disease may be positively associated with lung cancer risk by confounding of smoking, but not an independent risk factor.

Asporin Promotes TGF-ß-induced Lung Myofibroblast Differentiation by Facilitating Rab11-Dependent Recycling of TßRI.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease with high mortality and morbidity. ASPN (asporin), a member of the small leucine-rich proteoglycan family, plays crucial roles in tissue injury and regeneration. However, the precise pathophysiological role of ASPN and its molecular mechanisms in IPF remain unknown. We sought to investigate the role of ASPN during the development of pulmonary fibrosis and the therapeutic potential of targeting ASPN-related signaling pathways. In our study, three microarray datasets were downloaded from the Gene Expression Omnibus database, and differentially expressed genes were screened out by bioinformatic analysis. Hub genes were selected from the protein-protein interaction network. ASPN was examined in lung tissues from pulmonary fibrosis mouse models, and the role of ASPN in transforming growth factor (TGF)-ß/Smad signaling was determined by transfection with ASPN shRNA vectors in vitro. Biotinylation assays were conducted to measure plasma membrane TFG-ß receptor I (TßRI) and TßRI recycling after ASPN knockdown. The results showed ASPN expression was increased in the lungs of pulmonary fibrosis mouse models, and ASPN was primarily localized in α-SMA+ myofibroblasts. In vitro experiments proved that ASPN knockdown inhibited TGF-ß/Smad signaling and myofibroblast differentiation by regulating the stability of TßRI. Further molecular mechanisms revealed that ASPN knockdown inhibited TGF-ß/Smad signaling by suppressing recycling of TßRI to the cell surface in a Rab11-dependent manner and facilitated lysosome-mediated degradation of TßRI. In conclusion, our findings provide important evidence for the use of ASPN as a novel pharmacological target for treating pulmonary fibrosis.