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Treatments of inflammatory bowel disease (IBD) are diverse, but their efficacy is limited, and it is therefore urgent to find better therapies. Controlling mucosal inflammation is a must in IBD drug treatment. The occurrence of anti-tumor necrosis factor α (TNF-α) monoclonal antibodies has provided a safer and more efficacious therapy. However, this kind of treatment still faces failure in the form of loss of response. β-Carboline alkaloids own an anti-inflammatory pharmacological activity. While Kumujan B contains β-carboline, its biological activity remains unknown. In this study, we attempted to determine the anti-inflammatory effects of Kumujan B using both the TNF-α- induced in vitro inflammation and DSS-induced in vivo murine IBD models. Our data show that Kumujan B attenuated the expression of interleukin 1β (IL-1β) and interleukin 6 (IL-6) induced by TNF-α in mouse peritoneal macrophages. Kumujan B suppressed c-Jun N-terminal protein kinases (JNK) signaling, especially c-Jun, for anti-inflammatory response. Furthermore, Kumujan B promoted K11-linked ubiquitination and degradation of c-Jun through the proteasome pathway. In an in vivo study, Kumujan B inhibited the expression of IL-1β, IL-6, and TNF-α and improved the colon barrier function in dextran sulfate sodium salt (DSS)-induced experimental mice colitis. Kumujan B exhibited in vivo and in vitro anti-inflammatory effects, making it a potential therapeutic candidate for treating IBD.

The NLRP3 inflammasome plays a critical role in the innate immune response, and its excessive activation will cause pyroptotic cell death and be associated with the onset of inflammatory diseases. However, NLRP3 inflammasome targeting therapies are still to be implemented in the clinic setting. Here, we first isolated, purified and characterized a novel Vitenegu acid from V. negundo L. herb that specifically inhibits NLRP3 inflammasome activation, without affecting NLRC4 or AIM2 inflammasomes. Vitenegu acid blocks the oligomerization of NLRP3, thus inhibiting NLRP3 inflammasome assembly and activation. In vivo data show that Vitenegu acid exerts therapeutic effects on NLRP3 inflammasome-dependent inflammation. Taken together, our results suggest that Vitenegu acid is a candidate therapeutic agent for treating NLRP3 inflammasome related diseases.

Inflammatory bowel diseases (IBDs) are increasingly common diseases characterized by chronic and relapsing inflammation of the gastrointestinal tract. NLRP3 might be a crucial regulator of the homeostatic balance of the intestine, but its upregulation leads to pyroptosis. Munronoid I is extracted and purified from Munronia sinica, which has shown an anti-inflammatory effect, but the efficacy of Munronoid I in IBD remains unproven. In this study, we attempted to determine the effect of Munronoid I on NLRP3 to regulate the inflammasome activation and pyroptosis in IBD. Our data demonstrated that Munronoid I treatment attenuated DSS-induced body weight loss, pathological injury of the colon, the production of IL-1β and IL-18, and the expression of pyroptosis-associated proteins in colon tissue in mice. Moreover, Munronoid I inhibited LPS/ATP-induced pyroptosis in mouse peritoneal macrophages, MODE-K cells, and DSS-induced pyroptosis in mouse colonic epithelial cells, and decreased the release of inflammatory cytokines IL-1β and IL-18 in mouse peritoneal macrophages. Mechanically, Munronoid I could suppress the NLRP3 inflammasome activation and pyroptosis by promoting the K48-linked ubiquitination and NLRP3 degradation. It is suggested that Munronoid I might be a potential therapeutic candidate for IBD.

Improving energy efficiency of dishwasher products is not only critical for their market competitiveness, but also vital for reducing global carbon emission. To enhance their energy performance, previous studies developed models to simulate dishwashers' operating processes, but most investigations focused on simulating only a partial operating cycle, which was not sufficient for fully understanding the whole-cycle energy distribution. Besides, many simulations assumed constant heat transfer coefficient between tableware and washing fluid, leading to simulation inaccuracies. This research studied the heat transfer and energy distribution inside dishwasher by developing a conjugate 3D-1D simulation strategy, which modeled energy consumption based on dynamic HTC values and was validated by measured data. The simulated temperature and energy consumption results deviated from measurement by less than 0.5 °C and 35.7%, respectively, during a 300s heating process. Results also showed that 35.7% of consumed energy was absorbed by tableware as heat. This study not only established a novel simulation strategy that could calculate whole-cycle energy consumption and energy distributions in dishwashers with good accuracy, but also demonstrated dishwashers’ energy consumption could be reduced via design optimizations. By increasing insulation thickness from 20 mm to 40 mm alone, the total energy consumption was reduced by 8.4%.

Abstract Background The major histocompatibility complex (MHC) and the killer cell immunoglobulin-like receptors (KIR) are key regulators of immune responses. The cynomolgus macaque, an Old World monkey species, can be applied as an important preclinical model for studying human diseases, including coronavirus disease 2019 (COVID-19). Several MHC-KIR combinations have been associated with either a poor or good prognosis. Therefore, macaques with a well-characterized immunogenetic profile may improve drug evaluation and speed up vaccine development. At present, a complete overview of the MHC and KIR haplotype organizations in cynomolgus macaques is lacking, and characterization by conventional techniques is hampered by the extensive expansion of the macaque MHC-B region that complicates the discrimination between genes and alleles. Methods We assembled complete MHC and KIR genomic regions of cynomolgus macaque using third-generation long-read sequencing approach. We identified functional Mafa-B loci at the transcriptome level using locus-specific amplification in a cohort of 33 Vietnamese cynomolgus macaques. Results This is the first physical mapping of complete MHC and KIR gene regions in a Vietnamese cynomolgus macaque. Furthermore, we identified four functional Mafa-B loci (B2, B3, B5, and B6) and showed that alleles of the Mafa-I*01, -B*056, -B*034, and -B*001 functional lineages, respectively, are highly frequent in the Vietnamese cynomolgus macaque population. Conclusion The insights into the MHC and KIR haplotype organizations and the level of diversity may refine the selection of animals with specific genetic markers for future medical research.

To evaluate the clinical safety and efficacies of percutaneous vertebroplasty (PVP), percutaneous kyphoplasty (PKP), and percutaneous mesh-container-plasty (PMCP) for the treatment of vertebral compression fractures (VCFs), a retrospective study of 90 patients with VCFs who had been treated by PVP (n = 30), PKP (n = 30), and PMCP (n = 30) was conducted. The clinical efficacies of these three treatments were evaluated by comparing their PMMA cement leakages, cement patterns, height restoration percentages, wedge angles, visual analogue scales (VAS), and oswestry disability index (ODI) at the pre- and post-operative time points. 6.67%, 3.33%, and 0% of patients had PMMA leakage in PVP, PKP, and PMCP groups, respectively. Three (solid, trabecular, and mixed patterns), two (solid and mixed patterns), and one (mixed patterns) types of cement patterns were observed in PVP, PKP, and PMCP groups, respectively. PKP and PMCP treatments had better height restoration ability than PVP treatment. PVP, PKP, and PMCP treatments had significant and similar ability in pain relief and functional recovery ability for the treatment of VCFs. These results indicate minimally invasive techniques were effective methods for the treatment of VCFs. Moreover, these initial outcomes suggest PMCP treatment may be better than both PVP treatment and PKP treatment.