Symbiosis between Dendrobium catenatum protocorms and Serendipita indica involves the plant hypoxia response pathway.

Mycorrhizae are ubiquitous symbioses established between fungi and plant roots. Orchids, in particular, require compatible mycorrhizal fungi for seed germination and protocorm development. Unlike arbuscular mycorrhizal fungi, which have wide host ranges, orchid mycorrhizal fungi are often highly specific to their host orchids. However, the molecular mechanism of orchid mycorrhizal symbiosis is largely unknown compared to that of arbuscular mycorrhizal and rhizobial symbiosis. Here, we report that an endophytic Sebacinales fungus, Serendipita indica, promotes seed germination and the development of protocorms into plantlets in several epiphytic Epidendroideae orchid species (6 species in 2 genera), including Dendrobium catenatum, a critically endangered orchid with high medicinal value. Although plant-pathogen interaction and high meristematic activity can induce the hypoxic response in plants, it has been unclear whether interactions with beneficial fungi, especially mycorrhizal ones, also involve the hypoxic response. By studying the symbiotic relationship between D. catenatum and S. indica, we determined that hypoxia-responsive genes, such as those encoding alcohol dehydrogenase (ADH), are highly induced in symbiotic D. catenatum protocorms. In situ hybridization assay indicated that the ADH gene is predominantly expressed in the basal mycorrhizal region of symbiotic protocorms. Additionally, the ADH inhibitors puerarin and 4-methylpyrazole both decreased S. indica colonization in D. catenatum protocorms. Thus, our study reveals that S. indica is widely compatible with orchids and that ADH and its related hypoxia-responsive pathway are involved in establishing successful symbiotic relationships in germinating orchids.

Nuciferine Inhibits Oral Squamous Cell Carcinoma Partially through Suppressing the STAT3 Signaling Pathway.

Oral squamous cell carcinoma (OSCC) poses a significant obstacle to the worldwide healthcare system. Discovering efficient and non-toxic medications is crucial for managing OSCC. Nuciferine, an alkaloid with an aromatic ring, is present in the leaves of Nelumbo nucifera. It has been proven to play a role in multiple biological processes, including the inhibition of inflammation, regulation of the immune system, formation of osteoclasts, and suppression of tumors. Despite the demonstrated inhibitory effects of nuciferine on different types of cancer, there is still a need for further investigation into the therapeutic effects and potential mechanisms of nuciferine in OSCC. Through a series of in vitro experiments, it was confirmed that nuciferine hindered the growth, movement, and infiltration, while enhancing the programmed cell death of OSCC cells. Furthermore, the administration of nuciferine significantly suppressed the signal transducer and activator of transcription 3 (STAT3) signaling pathway in comparison to other signaling pathways. Moreover, the activation of the STAT3 signaling pathway by colivelin resulted in the reversal of nuciferine-suppressed OSCC behaviors. In vivo, we also showed the anti-OSCC impact of nuciferine using the cell-based xenograft (CDX) model in nude mice. Nonetheless, colivelin diminished the tumor-inhibiting impact of nuciferine, suggesting that nuciferine might partially impede the advancement of OSCC by suppressing the STAT3 signaling pathway. Overall, this research could offer a fresh alternative for the pharmaceutical management of OSCC.

Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission.

Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.

UBA domain protein SUF1 interacts with NatA-complex subunit NAA15 to regulate thermotolerance in Arabidopsis.

During recovery from heat stress, plants clear away the heat-stress-induced misfolded proteins through the ubiquitin-proteasome system (UPS). In the UPS, the recognition of substrate proteins by E3 ligase can be regulated by the N-terminal acetyltransferase A (NatA) complex. Here, we determined that Arabidopsis STRESS-RELATED UBIQUITIN-ASSOCIATED-DOMAIN PROTEIN FACTOR 1 (SUF1) interacts with the NatA complex core subunit NAA15 and positively regulates NAA15. The suf1 and naa15 mutants are sensitive to heat stress; the NatA substrate N SNC1 is stabilized in suf1 mutant plants during heat stress recovery. Therefore, SUF1 and its interactor NAA15 play important roles in basal thermotolerance in Arabidopsis.

Lipid/PAA-coated mesoporous silica nanoparticles for dual-pH-responsive codelivery of arsenic trioxide/paclitaxel against breast cancer cells.

Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pHe = 6.5, pHendo = 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.

All-trans retinoic acid induces anti-tumor effects via STAT3 signaling inhibition in oral squamous cell carcinoma and oral dysplasia.

BACKGROUND: Oral squamous cell carcinoma (OSCC), which may arise from oral dysplasia, is one of the most prevalent cancers around the world. In recent years, all-trans retinoic acid (ATRA) has shown great potential in cancer treatment. However, the molecular mechanism for the anti-tumor effects of ATRA remains unclear. MATERIALS AND METHODS: After treated with ATRA, inhibition of cell proliferation of OSCC and oral dysplasia cell lines, CAL27 and DOK, respectively, was analyzed by a Cell Counting Kit-8 (CCK8) assay. The cell cycle arrest, cell apoptosis induction, and PD-L1 expression level were measured by flow cytometry. A small molecular inhibitor was utilized to block STAT3 pathway, and the related proteins expression was measured by Western Blot. RESULTS: The present study demonstrated that ATRA inhibited cell proliferation at 5-75 µmol/L, arrested cell cycle at S and G2-phase, induced apoptosis effect in OSCC, and oral dysplasia cell line, CAL27 and DOK, respectively. ATRA led to inhibition of p-STAT3, p-JAK2, increased the level of p-ERK, and significantly decreased the PD-L1 expression. Moreover, targeting STAT3 signaling increased (P < .001) the level of cleaved caspase-3 and effectively (P < .001) decreased the expression of cyclin A2 and PD-L1. The effect of ATRA on cell growth inhibition, apoptosis induction, and PD-L1 expression decrease was significantly (P < .05) enhanced after the STAT3 signaling blockade. CONCLUSION: These findings suggested that ATRA-induced anti-tumor effects and downregulated PD-L1 expression via STAT3 signaling inhibition in both OSCC and oral dysplasia.

[Preparation of angiopep-2-modified FITC-labeled neurotoxin nanoparticles and in vitro release characteristics].

In order to prepare angiopep-2 modified fluorescein isothiocyanate-labeled neurotoxin nanoparticles( ANG-NPs/FITCNT),emulsion/solvent evaporation method was used with m PEG-PLA and ANG-PEG-PLA( in proper proportions) as carriers and with FITC-NT as drug. With particle size and encapsulation efficiency as comprehensive indexes,the effects of different ultrasound power and ultrasound time combinations on the process were investigated. The in vitro release characteristics of nanoparticles in PBS buffer at p H 7. 4 and p H 6. 5 were investigated by dialysis method. The results indicated that the optimum process for preparing ANG-NPs/FITC-NT was as follows: ultrasonic power 90 W,ultrasonic time 30 s. In such optimal process,ANG-NPs/FITC-NT were well-shaped under the transmission electron microscope,with an average particle size of( 123. 9±0. 5) nm,Zeta potential of(-10. 5±0. 5) m V,encapsulation efficiency of( 68. 1±0. 4) %,and the drug loading of( 0. 82±0. 01) %. The in vitro drug release profiles of the nanoparticles in PBS buffer at p H 7. 4 and p H 6. 5 were both consistent with Ritger-Peppas equation,ln Q = 0. 508 8 lnt-2. 285 0,r = 0. 961 5( p H 7. 4) and ln Q= 0. 449 9 lnt-1. 855 3,r = 0. 970 3( p H 6. 5),respectively. The experiment results proved that the nanoparticles prepared by emulsion/solvent evaporation method had uniform particle size,high encapsulation efficiency and in vitro sustained release characteristic,which might be a potential carrier for NT intracerebral drug delivery.

Nanotechnology: a promising method for oral cancer detection and diagnosis.

Oral cancer is a common and aggressive cancer with high morbidity, mortality, and recurrence rate globally. Early detection is of utmost importance for cancer prevention and disease management. Currently, tissue biopsy remains the gold standard for oral cancer diagnosis, but it is invasive, which may cause patient discomfort. The application of traditional noninvasive methods-such as vital staining, exfoliative cytology, and molecular imaging-is limited by insufficient sensitivity and specificity. Thus, there is an urgent need for exploring noninvasive, highly sensitive, and specific diagnostic techniques. Nano detection systems are known as new emerging noninvasive strategies that bring the detection sensitivity of biomarkers to nano-scale. Moreover, compared to current imaging contrast agents, nanoparticles are more biocompatible, easier to synthesize, and able to target specific surface molecules. Nanoparticles generate localized surface plasmon resonances at near-infrared wavelengths, providing higher image contrast and resolution. Therefore, using nano-based techniques can help clinicians to detect and better monitor diseases during different phases of oral malignancy. Here, we review the progress of nanotechnology-based methods in oral cancer detection and diagnosis.

Incidence and risk assessment of venous thromboembolism in cancer patients admitted to intensive care unit for postoperative care.

PURPOSE: The occurrence of venous thromboembolism (VTE) in Chinese cancer patients admitted to intensive care unit (ICU) for postoperative care is poorly characterized. This study was designed to investigate the incidence of VTE in this polulation and to evaluate the utility of the Caprini score in risk stratification. METHODS: We conducted a retrospective cohort study of 2127 consecutive adult patients admitted to a 10-bed surgical ICU in a tertiary care academic hospital during a 4-year period (January 1,2013 to December 31,2016). Demographic and VTE data were collected. Data for the Caprini risk assessment model (RAM) was used to stratify patients on their risk of VTE. RESULTS: Of the 2127 patients admitted to ICU after cancer surgery, 66 (3.1%) developed symptomatic VTE. There were a total of 32 patients with pulmonary embolism (PE), 51 patients with deep vein thrombosis (DVT), and 17 patients with both conditions. Based on the original Caprini RAM, 99.5% of the patients scored in the "highest risk" category (score≥5), all patients with VTE were in the "highest risk" category. Further substratification in the "highest risk" category showed the risk of developing VTE events were significantly higher among patients with Caprini score >10 ,as compared with patients with Caprini score of 5 to 6 (OR 5.63; 95%CI 1.27-24.94), 7 to 8 (OR 2.36; 95% CI 1.23-4.52 ) or 9 to 10 (OR 2.28; 95%CI 1.17-4.44). The percentage of patients receiving double prophylaxis was 16.8% (358/2127), 20 of the 66 VTE patients (30.3%) received double prophylaxis before VTE was diagnosed. Patients with higher Caprini score were more likely to receive double thromboprophylaxis than patients with lower Caprini score (23.4% of patients with Caprini score>10 vs 10.8% with Caprini score 5-6). CONCLUSIONS: Though accompanying with the sub-utilizing of chemoprophylaxis, the overall incidence of VTE was relatively low in Chinese cancer patients admitted to ICU for postoperative care. In contrast, the Caprini score was high in this population. The original Caprini RAM was limited to stratify this population, but further substratification of "highest risk" category demonstrated the risk of developing VTE events was significantly higher in patients with Caprini score >10. Future research with high quality evidence should be performed targeting on the accurate risk stratification and optimizing VTE prophylaxis for this population.

Incidence and risk assessment of venous thromboembolism in cancer patients admitted to intensive care unit for postoperative care.

PURPOSE: Cancer patients undergoing surgery are at high risk of venous thromboembolism (VTE). The occurrence of VTE in Chinese cancer patients admitted to intensive care unit (ICU) for postoperative care is poorly characterized. This study was designed to investigate the incidence of VTE in this population and to evaluate the utility of the Caprini score in risk stratification. METHODS: 2127 consecutive adult patients admitted to a 10-bed surgical ICU (SICU) in a tertiary care academic hospital during a 4-year period (January 1, 2013 - December 31, 2016) were enrolled. Demographic and VTE data were collected. Data for the Caprini risk assessment model (RAM) was used to stratify patients on their risk of VTE. RESULTS: Of the 2127 patients admitted to ICU after cancer surgery, 66 (3.1%) developed symptomatic VTE. There were a total of 32 patients with pulmonary embolism (PE), 51 patients with deep vein thrombosis (DVT) and 17 patients with both conditions. Based on the original Caprini RAM, 99.5% of the patients scored in the "highest risk" category (score ≥5), all patients with VTE were in the "highest risk" category. Further substratification in the "highest risk" category showed the risk of developing VTE events was significantly higher among patients with Caprini score greater than 10, as compared with patients with Caprini score of 5 to 6 (OR 5.63;95%CI 1.27-24.94), 7 to 8 (OR 2.36;95%CI 1.23-4.52 ) or 9 to 10 (OR 2.28;95%CI 1.17-4.44). The percentage of patients receiving double prophylaxis was 16.8% (358/2127), 20 of the 66 VTE patients (30.3%) received double prophylaxis before VTE was diagnosed. Patients with higher Caprini score were more likely to receive double thromboprophylaxis than patients with lower Caprini score (23.4% of patients with Caprini score>10 vs 10.8% with Caprini score 5-6). CONCLUSIONS: Though accompanied with the subutilizing of chemoprophylaxis, the overall incidence of VTE was relatively low in Chinese cancer patients admitted to ICU for postoperative care. In contrast, the Caprini score was high in this population. The original Caprini RAM was limited to stratify this population, but further substratification of "highest risk" category demonstrated the risk of developing VTE events was significantly higher in patients with Caprini score greater than 10. Future research with high quality evidence should be performed targeting on the accurate risk stratification and optimizing VTE prophylaxis for this population.

Impact of plasmid-borne oqxAB on the development of fluoroquinolone resistance and bacterial fitness in Escherichia coli.

Objectives: To investigate the impact of plasmid-borne oqxAB genes on the development of fluoroquinolone resistance, mutations and bacterial fitness in Escherichia coli . Methods: MICs and mutation prevention concentrations were compared among E. coli strain TOP10 and two corresponding transformants harbouring the OqxAB-encoding plasmids. Mutants were selected by serial passages with the 0.5-fold MIC of ciprofloxacin, and were randomly selected to determine mutations. Bacterial fitness was evaluated by competition assays in vitro and in vivo . Results: The oqxAB -carrying plasmids contributed to a 4-8-fold increase in the ciprofloxacin MIC and increased the ciprofloxacin mutation prevention concentration by 8-16-fold. The MIC of ciprofloxacin for the two transformants increased faster than that of E. coli TOP10 by serial passaging. Novel mutations in gyrB (A468P or F458V) were first observed. Mutations in gyrA were distributed at codons 87 and 83 in the two transformants, whereas mutation A119E in gyrA dominated in the TOP10 mutants. Although the two oqxAB -bearing plasmids caused a decrease in fitness in vitro , their fitness increased when combined with more than one chromosomal mutation, and clear biological benefits were observed in vivo . The mutations in gyrB were associated with a fitness cost, which could be compensated for by additional mutations. The novel mutation gyrA ΔS83 significantly reduced biological fitness both in vitro and in vivo , and was thus quickly replaced by more beneficial mutations in the population. Conclusions: The possession of plasmid-borne oqxAB may facilitate the evolution of fluoroquinolone resistance, and the fitness cost of OqxAB-encoding plasmids could be compensated by additional chromosomal mutations.

Specifically targeting mixed-type dimeric G-quadruplexes using berberine dimers.

Three polyether-tethered berberine dimers (1a-c) were studied for their binding affinity, selectivity and thermal stabilization towards human telomeric dimeric quadruplex DNA (G2T1). Compound 1a with the shortest polyether linker showed the highest affinity (Ka > 108 M-1) and 76-508-fold higher selectivity for mixed-type G2T1 over antiparallel G2T1 and three monomeric G-quadruplexes, which are human telomeric monomeric quadruplex G1, c-kit 1 and c-kit 2. Compound 1a induced the formation of quadruplex structures and showed higher thermal stabilization for mixed-type G2T1 than for anti-parallel G2T1, G1 and ds DNA. Spectroscopic studies suggest that compound 1a could bind to mixed-type G2T1 via end-stacking and external binding modes. These results suggest that the polyether linkers in these compounds play an important role in regulating the binding affinity and selectivity towards mixed-type G2T1 and that compound 1a could target mixed-type G2T1 at other genome regions with antiparallel G2T1 and monomeric G-quadruplexes. These results may provide useful guidance for the rational design of selective multimeric G-quadruplex binders and potential anticancer agents.

Pulmonary embolism in non-brain tumor patients after surgery-a retrospective study in China.

BACKGROUND: The incidence rate of pulmonary emboli (PE) is high in tumor patients; however, the morbidity and mortality associated with the development of PE after tumor surgery are unknown. We studied the clinical profiles and outcomes of patients with PE after non-brain tumor surgery. METHODS: We retrospectively screened 55,967 patients who underwent non-brain tumor surgery at the Peking University Cancer Hospital from January 2008 to June 2015. Among them, 76 patients who were diagnosed with PE were enrolled in our study. Factors impacting the overall survival at 90 days were analyzed. A Kaplan-Meier curve was plotted for time to death or until day 90. Cox proportional hazard modeling was performed for univariate- and multivariate-adjusted factor analyses. RESULTS: The morbidity rate was approximately 135.8 per 100,000 non-brain tumor surgery patients (possibly underestimated). When treated, seven patients had major bleeding, and 14 patients had clinically relevant non-major bleeding, which represented 9.2 and 18.4% of all the patients, respectively. The 3-month overall mortality rate was 11.8% in our study. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score and platelet distribution width (PDW) were independent risk factors for the prognosis of PE after non-brain surgery (P values of 0.001 and 0.016, respectively). CONCLUSIONS: Treatment of PE in non-brain tumor surgical patients remained a challenge due to the high bleeding rate. The APACHE II score and PDW were independent prognostic factors of survival in patients with PE after non-brain tumor surgery; however, the study power was limited.

Human CD8(+) T cells transduced with an additional receptor bispecific for both Mycobacterium tuberculosis and HIV-1 recognize both epitopes.

Tuberculosis (TB) and human immunodeficiency virus type 1 (HIV-1) infection are closely intertwined, with one-quarter of TB/HIV coinfected deaths among people died of TB. Effector CD8(+) T cells play a crucial role in the control of Mycobacterium tuberculosis (MTB) and HIV-1 infection in coinfected patients. Adoptive transfer of a multitude of effector CD8(+) T cells is an appealing strategy to impose improved anti-MTB/HIV-1 activity onto coinfected individuals. Due to extensive existence of heterologous immunity, that is, T cells cross-reactive with peptides encoded by related or even very dissimilar pathogens, it is reasonable to find a single T cell receptor (TCR) recognizing both MTB and HIV-1 antigenic peptides. In this study, a single TCR specific for both MTB Ag85B199-207 peptide and HIV-1 Env120-128 peptide was screened out from peripheral blood mononuclear cells of a HLA-A*0201(+) healthy individual using complementarity determining region 3 spectratype analysis and transferred to primary CD8(+) T cells using a recombinant retroviral vector. The bispecificity of the TCR gene-modified CD8(+) T cells was demonstrated by elevated secretion of interferon-γ, tumour necrosis factor-α, granzyme B and specific cytolytic activity after antigen presentation of either Ag85B199-207 or Env120-128 by autologous dendritic cells. To the best of our knowledge, this study is the first report proposing to produce responses against two dissimilar antigenic peptides of MTB and HIV-1 simultaneously by transfecting CD8(+) T cells with a single TCR. Taken together, T cells transduced with the additional bispecific TCR might be a useful strategy in immunotherapy for MTB/HIV-1 coinfected individuals.

Absence of high-risk HPV 16 and 18 in Chinese patients with oral squamous cell carcinoma and oral potentially malignant disorders.

BACKGROUND: The critical role of human papillomavirus (HPV) in cancer has been recognized, but the involvement of HPV in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) is still controversial. The aim of this study was to identify and verify the prevalence of high-risk HPV infection (HPV16 and 18) in Chinese patients with OSCC or OPMD using real-time PCR and DNA sequencing. METHODS: Paired tissue and serum DNA samples were extracted from 40 Chinese patients with OSCC and 59 with OPMD. A SYBR Green-based real-time PCR assay was developed to detect the E6 gene of HPV16 and HPV18. Suspicious positive samples were then sequenced to eliminate false positives. RESULTS: We found that none of the tissue and serum samples of OSCCs and OPMDs were positive for HPV16 E6 or 18 E6, using both real-time PCR and DNA sequencing. Overall, 3 of 198 (1.52 %) and 7 of 198 (3.54 %) samples were false-positive for HPV16 E6 and HPV18 E6, respectively, using real-time PCR. CONCLUSION: The lack of HPV16 and HPV18 detected in this study indicates that high-risk HPV 16 and 18 infections are uncommon in Chinese patients with OSCC and OPMD. Real-time PCR followed by DNA sequencing for HPV DNA detection is an effective strategy to rule out false positives.

Distribution of the Multidrug Resistance Gene cfr in Staphylococcus Isolates from Pigs, Workers, and the Environment of a Hog Market and a Slaughterhouse in Guangzhou, China.

Bacteria harboring cfr, a multidrug resistance gene, have high prevalence in livestock in China and might be transmitted to humans through direct contact or via contaminated food products. To better understand the epidemiology of cfr producers in the food chain, the prevalence and genetic analysis of Staphylococcus isolates recovered from pigs, workers, and meat-handling facilities (a slaughterhouse and a hog market in Guangzhou, China) were examined. Twenty (4.5%) cfr-positive Staphylococcus isolates (18 Staphylococcus simulans, 1 S. cohnii, and 1 S. aureus) were derived from pigs (16/312), the environment (2/52), and workers (2/80). SmaI pulsed-field gel electrophoresis of 26 staphylococcal strains (22 S. simulans and 4 S. cohnii), including previously reported cfr-carrying staphylococci of animal food origin, exhibited 19 major pulsed-field gel electrophoresis patterns (A-S). Clonal spread of cfr-carrying staphylococci among pigs, workers, and meat products was detected. The genetic contexts of cfr in plasmids (pHNKF3, pHNZT2, and pHNCR35) obtained from S. simulans of swine or human origin were similar to that of Staphylococcus species isolated from human clinics and animal-derived food. The cfr-carrying S. aureus strain isolated from floor swabs of the hog market was spa-type t889 and belonged to the ST9 clonal lineage. In summary, both clonal spread and horizontal transmission via mobile elements contributed to cfr dissemination among staphylococcal isolates obtained from different sources. To monitor potential outbreaks of cfr-positive bacteria, continued surveillance of this gene in animals at slaughter and in animal-derived food is warranted.

Lipid droplets' functional protein caveolin-2 is associated with lipid metabolism-related molecule FABP5 and EMT marker E-cadherin in oral epithelial dysplasia.

AIMS: To explore the accumulation of lipid droplets (LDs) and its relationship with lipid metabolism, and epithelial-mesenchymal transition (EMT) in the carcinogenesis processes in the oral cavity. METHODS: LDs were stained by oil red O. Forty-eight oral squamous cell carcinomas (OSCC), 78 oral potentially malignant disorders (OPMDs) and 25 normal tissue sections were included to explore the LDs surface protein caveolin-2 and perilipin-3, lipid metabolism-related molecule FABP5 and EMT biomarker E-cadherin expression by immunohistochemical staining. RESULTS: The accumulation of LDs was observed in OPMDs and OSCCs compared with normal tissues (p<0.05). In general, an increasing trend of caveolin-2, perilipin-3 and FABP5 expression was detected from the normal to OPMDs to OSCC groups (p<0.05). Additionally, caveolin-2, perilipin-3 and FABP5 expression were positively correlated with epithelial dysplasia in OPMDs, whereas E-cadherin positivity was negatively correlated with histopathological grade in both OPMDs and OSCC, respectively. A negative correlation of caveolin-2 (p<0.01, r =-0.1739), and FABP5 (p<0.01, r =-0.1880) with E-cadherin expression was detected. The caveolin-2 (p<0.0001, r=0.2641) and perilipin-3 (p<0.05, r=0.1408) staining was positively correlated with FABP5. Increased caveolin-2 expression was related to local recurrence and worse disease-free survival (p<0.05). CONCLUSION: In the oral epithelial carcinogenesis process, LDs begin to accumulate early in the precancerous stage. LDs may be the regulator of FABP5-associated lipid metabolism and may closely related to the process of EMT; caveolin-2 could be the main functional protein.

The Potential of Lipid Droplet-associated Genes as Diagnostic and Prognostic Biomarkers in Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: The role of lipid droplets (LDs) and lipid droplet-associated genes (LD-AGs) remains unclear in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate LDs in HNSCC and identify LD-AGs essential for the diagnosis and prognosis of HNSCC patients. METHODS: The LDs in the HNSCC and normal cell lines were stained with oil red O. Bioinformatic analysis was used to find LD-AGs in HNSCC that had diagnostic and prognostic significance. RESULTS: LDs accumulation was increased in HNSCC cell lines compared with normal cell lines (P<0.05). Fifty-three differentially expressed genes, including 34 upregulated and 19 downregulated, were found in HNSCC based on the TCGA platform (P<0.05). Then, 53 genes were proved to be functionally enriched in lipid metabolism and LDs. Among them, with an AUC value > 0.7, 34 genes demonstrated a high predictive power. Six genes (AUP1, CAV1, CAV2, CAVIN1, HILPDA, and SQLE) out of 34 diagnostic genes were linked to overall survival in patients with HNSCC (P<0.05). The significant prognostic factors AUP1, CAV1, CAV2, and SQLE were further identified using the univariate and multivariate cox proportional hazard models (P<0.05). The protein expression of CAV2 and SQLE was significantly increased in the HNSCC tissue compared to normal tissues (P<0.05). Finally, the knockdown of the four LD-AGs decreased LDs accumulation, respectively. CONCLUSIONS: Increased LDs accumulation was a hallmark of HNSCC, and AUP1, CAV1, CAV2, and SQLE were discovered as differentially expressed LD-AGs with diagnostic and prognostic potential in HNSCC.

Analysis of Microbial Diversity and Community Structure of Rhizosphere Soil of Three Astragalus Species Grown in Special High-Cold Environment of Northwestern Yunnan, China.

Astragalus is a medicinal plant with obvious rhizosphere effects. At present, there are many Astragalus plants with high application value but low recognition and resource reserves in the northwestern area of Yunnan province, China. In this study, metagenomics was used to analyze the microbial diversity and community structure of rhizosphere soil of A. forrestii, A. acaulis, and A. ernestii plants grown in a special high-cold environment of northwestern Yunnan, China, at different altitudes ranging from 3225 to 4353 m. These microbes were taxonomically annotated to obtain 24 phyla and 501 genera for A. forrestii, 30 phyla and 504 genera for A. acaulis, as well as 39 phyla and 533 genera for A. ernestii. Overall, the dominant bacterial phyla included Proteobacteria, Actinobacteria, and Acidobacteria, while the dominant fungal ones were Ascomycota and Basidiomycota. At the genus level, Bradyrhizobium, Afipia, and Paraburkholderia were the most prevalent bacteria, and Hyaloscypha, Pseudogymnoascus, and Russula were the dominant fungal genera. Some of them are considered biocontrol microbes that could sustain the growth and health of host Astragalus plants. Redundancy analysis revealed that pH, TN, and SOM had a significant impact on the microbial community structures (p < 0.05). Finally, triterpene, flavonoid, polysaccharide, and amino acid metabolisms accounted for a high proportion of the enriched KEGG pathways, which possibly contributed to the synthesis of bioactive constituents in the Astragalus plants.

Gene association analysis to determine the causal relationship between immune cells and juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a type of chronic childhood arthritis with complex pathogenesis. Immunological studies have shown that JIA is an acquired self-inflammatory disease, involving a variety of immune cells, and it is also affected by genetic and environmental susceptibility. However, the precise causative relationship between the phenotype of immune cells and JIA remains unclear to date. The objective of our study is to approach this inquiry from a genetic perspective, employing a method of genetic association analysis to ascertain the causal relationship between immune phenotypes and the onset of JIA. METHODS: In this study, a two-sample Mendelian randomization (MR) analysis was used to select single nucleotide polymorphisms (SNPs) significantly associated with immune cells as instrumental variables to analyze the bidirectional causal relationship between 731 immune cells and JIA. There were four types of immune features (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)). Finally, the heterogeneity and horizontal reproducibility of the results were verified by sensitivity analysis, which ensured more robust results. RESULTS: We found that CD3 on CM CD8br was causally associated with JIA at the level of 0.05 significant difference (95% CI = 0.630 ~ 0.847, P = 3.33 × 10-5, PFDR = 0.024). At the significance level of 0.20, two immunophenotypes were causally associated with JIA, namely: HLA DR on CD14+ CD16- monocyte (95% CI = 0.633 ~ 0.884, P = 6.83 × 10-4, PFDR = 0.16) and HLA DR on CD14+ monocyte (95% CI = 0.627 ~ 0.882, P = 6.9 × 10-4, PFDR = 0.16). CONCLUSION: Our study assessed the causal effect of immune cells on JIA from a genetic perspective. These findings emphasize the complex and important role of immune cells in the pathogenesis of JIA and lay a foundation for further study of the pathogenesis of JIA.