Exploring the causal role of gut microbiota in giant cell arteritis: a Mendelian randomization analysis with mediator insights.

Background: Giant Cell Arteritis (GCA) is a complex autoimmune condition. With growing interest in the role of gut microbiota in autoimmune diseases, this research aimed to explore the potential causal relationship between gut microbiota and GCA, and the mediating effects of specific intermediaries. Methods: Using a bidirectional two-sample Mendelian randomization (MR) design, we investigated associations between 191 microbial taxa and GCA. A two-step MR technique discerned the significant mediators on this relationship, followed by Multivariable MR analyses to quantify the direct influence of gut microbiota on GCA and mediation effect proportion, adjusting for these mediators. Results: Nine taxa displayed significant associations with GCA. Among them, families like Bacteroidales and Clostridiaceae1 had Odds Ratios (OR) of 1.48 (p=0.043) and 0.52 (p=5.51e-3), respectively. Genera like Clostridium sensu stricto1 and Desulfovibrio showed ORs of 0.48 (p=5.39e-4) and 1.48 (p=0.037), respectively. Mediation analyses identified 25 hydroxyvitamin D level (mediation effect of 19.95%), CD14+ CD16- monocyte counts (mediation effect of 27.40%), and CD4+ T cell counts (mediation effect of 28.51%) as significant intermediaries. Conclusion: Our findings provide invaluable insights into the complex interplay between specific gut microbiota taxa and GCA. By highlighting the central role of gut microbiota in influencing GCA risk and long-term recurrence, and their interactions with vital immune mediators, this research paves the way for potential therapeutic interventions in GCA management.

Intrinsically Self-Healable and Wearable All-Organic Thermoelectric Composite with High Electrical Conductivity for Heat Harvesting.

The development of wearable electronics has led to the growing demand for the self-powered and maintenance-free power sources. Under these circumstances, thermoelectric generators are considered promising candidates, which can directly convert body heat into electricity to power wearable electronics. However, most of the thermoelectric materials are either brittle or unrecoverable under external physical damage. It is urgent to develop thermoelectric materials that possess both stretchability and intrinsic self-healing property, and the remaining challenge is to combine the high mechanical robustness and excellent electrical conductivity. Herein, a self-healing and wearable all-organic thermoelectric composite is reported. The composite film exhibits high electrical conductivity of 238 S cm-1, high flexibility of up to 119% strain, and a maximum tensile strength of 23 MPa. When the composite film is subjected to external physical damage, most functionalities can be maintained after self-healing, 78% recovery in electrical conductivity, and 80% recovery in tensile strength. Using the self-healing composite, we fabricated a thermoelectric generator with a power output of 85.5 nW at a temperature difference of 48 K, which is a significant advance over the recently reported thermoelectric generators based on intrinsic self-healing thermoelectric materials. This work represents a crucial step toward achieving intrinsic self-healing all-organic thermoelectric materials with high electrical conductivity.

Observation and analysis of the efficacy of dexamethasone in combination with anti-infectious treatment on the pediatric refractory purulent meningitis.

To analyze the pathogenic bacteria, feature of drug resistance and the efficacy of dexamethasone as the auxiliary medication in pediatric refractory purulent meningitis (PM). The 190 refractory PM child patients were selected for the culture of pathogenic bacteria and analysis of drug resistance. In total, 190 pathogenic bacteria were detected, consisting of gram-positive bacteria (77.37%). Of the gram-positive bacteria, the resistance rate of patients with staphylococcus epidermidis, streptococcus pneumoniae or Staphylococcus haemolyticus to levofloxacin was 100%, while in gram-negative bacteria, the resistance rate of patients with klebsiella pneumoniae to gentamycin was 100%. In the observation group, patients had a higher effectiveness rate. Besides, patients in the observation group recovered rapidly from the fever and anomalies in cerebral spine fluid and peripheral white blood cells, and the inflammation was greatly improved. However, difference in the incidence rates of adverse reactions of patients between two groups showed no statistical significance. Pediatric refractory PM involves the pathogenic bacteria, mainly including staphylococcus epidermidis and streptococcus pneumoniae, showing a high resistance to levofloxacin, while the auxiliary medication of dexamethasone can improve the efficacy, and inhibit the inflammation.

From Anilines to Quinolines: Iodide- and Silver-Mediated Aerobic Double C-H Oxidative Annulation-Aromatization.

Quinoline synthesis from easily accessible raw materials such as anilines is a valuable and meaningful task. Herein, we communicate an iodide- and silver-mediated C-H/C-H oxidative annulation-aromatization between anilines and allyl alcohols. This protocol provides a direct route to the synthesis of quinoline derivatives from inexpensive commodities. Various kinds of anilines, even heterocyclic anilines, were shown to be workable substrates, generating the corresponding multi-substituted quinolines in good yields.

Evidence of Cu(I)/Cu(II) Redox Process by X-ray Absorption and EPR Spectroscopy: Direct Synthesis of Dihydrofurans from ß-Ketocarbonyl Derivatives and Olefins.

The Cu(I)/Cu(II) and Cu(I)/Cu(III) catalytic cycles have been subject to intense debate in the field of copper-catalyzed oxidative coupling reactions. A mechanistic study on the Cu(I)/Cu(II) redox process, by X-ray absorption (XAS) and electron paramagnetic resonance (EPR) spectroscopies, has elucidated the reduction mechanism of Cu(II) to Cu(I) by 1,3-diketone and detailed investigation revealed that the halide ion is important for the reduction process. The oxidative nature of the thereby-formed Cu(I) has also been studied by XAS and EPR spectroscopy. This mechanistic information is applicable to the copper-catalyzed oxidative cyclization of ß-ketocarbonyl derivatives to dihydrofurans. This protocol provides an ideal route to highly substituted dihydrofuran rings from easily available 1,3-dicarbonyls and olefins.

Copper-catalyzed radical carbooxygenation: alkylation and alkoxylation of styrenes.

A simple copper-catalyzed direct radical carbooxygenation of styrenes is developed utilizing alkyl bromides as radical resources. This catalytic radical difunctionalization accomplishes both alkylation and alkoxylation of styrenes in one pot. A broad range of styrenes and alcohols are well tolerated in this transformation. The EPR experiment shows that alkyl halides could oxidize Cu(I) to Cu(II) in this transformation.

Copper-catalysed direct radical alkenylation of alkyl bromides.

A copper-catalysed direct radical alkenylation of various benzyl bromides and α-carbonyl alkyl bromides has been developed. Compared with the recent radical alkenylations which mostly focused on secondary or tertiary alkyl halides, this transformation shows good reactivity to primary alkyl halides and tertiary, secondary alkyl halides were also tolerated. The key initiation step of this transformation is a copper-induced single-electron reduction of C-Br bonds to generate alkyl radical species.

[Isolation of rabbit aqueous humor-derived exosomes and their immunosuppression function].

OBJECTIVE: To isolate exosomes from rabbit aqueous humor and to investigate their immunosuppression function. METHODS: Aqueous humor was collected from 40 New Zealand rabbits and exosomes were isolated by fractional separation and ultracentrifugation methods; the morphology was studied with electron microscopy. The immunosuppressive-related proteins of exosomes were detected with Western blotting; their inhibitory effect on ConA-induced proliferation of T lymphocyte was estimation with CCK-8 cells proliferation assay. RESULTS: Eight milliliters of aqueous humor were collected from 40 New Zealand rabbits and 200 µg exosomes was yielded. Under electron microscope, the exosomes had typical structure of lipid bi-layer with a diameter of 50-100 nm. The results of Western blotting showed that these exosomes expressed Hsp70, CD9 and Alix but not Grp94, presenting a typical exosomes protein profile. Moreover, exosomes expressed high level of TGF-ß and significantly inhibited the proliferation of T lymphocytes. CONCLUSION: Immunosuppressive exosomes can be isolated from rabbit aqueous humor, which may be involved in immunotolerance of the eye.

Anticancer, antioxidant and antimicrobial activities of the essential oil of Lycopus lucidus Turcz. var. hirtus Regel.

This study was designed to examine the anticancer, antioxidant and antimicrobial activities of the essential oil from Lycopus lucidus Turcz. var. hirtus Regel. The essential oil treatment to six human cancer cell lines resulted in a dose-dependent inhibition of cell growth. The cytotoxicity of the essential oil on liver carcinoma and breast cancer cell lines was significantly stronger than on other cell lines. The essential oil can induce apoptosis of the liver carcinoma cell line Bel-7402 and decrease the intracellular GSH level. The antioxidant effect of the essential oil was evaluated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical (OH) scavenging assays. The essential oil exhibited moderate antioxidant activity. The antimicrobial activity of the essential oil was evaluated against eight microorganisms using the disc diffusion and broth microdilution methods. The essential oil also showed moderate antimicrobial activity. These suggest that the essential oil could hold a good potential for use in the pharmaceutical industry.

[Preparation of monoclonal antibodies against human mesenchymal stem cells].

OBJECTIVE: To prepare monoclonal antibodies (McAbs) against human mesenchymal stem cells (hMSCs) and to study their biological characteristics. METHODS: BALB/C mice were immunized with pooled hMSCs. McAbs were prepared by hybridoma technique and their biological characteristics were analyzed by indirect immunofluorescence, immunohistochemistry and flow cytometry. RESULT: Five hybridoma cell lines were successfully established, which secret McAbs specifically against hMSCs. Investigations showed that all these McAb reacted only to hMSCs and had no cross-reaction to other human cells, the relative affinities of 5 McAbs were 1x10(6) (ZUB1), 1x10(5) (ZUB4), 1x10(6) (ZUC3), ZUE12 (1x10(5)) and 1x10(5) (ZUF10), respectively. Isotype analysis showed that ZUB1, ZUE12, ZUF10 against the same isotype, while ZUC3, ZUB4 against other two different isotypes alone. Flow cytometric analysis showed that the positive expression rate of cultured hMSCs was 87.39% (ZUB1), 88.07% (ZUB4), 88.12% (ZUC3), 69.89% (ZUE12) and 83.67% (ZUF10). CONCLUSION: The prepared five McAbs can specifically react against hMSCs, which can be used for selection and study of hMCSs.

[Construction of recombinant plasmid containing mouse vasoactive intestinal peptide gene and its expression in COS-7 cells].

OBJECTIVE: To construct the eukaryotic expression plasmid containing mouse vasoactive intestinal peptide(VIP) gene with biological activities. METHODS: VIP cDNA including the sequences of signal peptide was cloned from mouse thymus by RT-PCR, and then inserted into the mammalian expression vector pcDNA3.1 between Hind III and EcoR I restriction sites. COS-7 cells were transfected with pcDNA3. 1-VIP using liposome, the expression of VIP was identified by Western blot and ELISA. Supernatant of transfected cell culture was added to LPS-stimulated macrophages and the TNF-alpha production in cell medium was observed by ELISA. RESULTS: The cloned VIP cDNA was confirmed by enzyme digestion and DNA sequencing. The expression of VIP was detected in the pcDNA3. 1-VIP transfected COS-7 cells by Western blot and ELISA. The VIP in culture supernatant potently inhibited TNF-alpha production by LPS-induced Macrophages in vitro. CONCLUSION: The eukaryotic expression plasmid that expresses biological active murine VIP has been constructed successfully.