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Plume are common physical phenomena in fiber laser keyhole welding and have serious negative effects on the welding process. Based on this, this paper explores the regulation law of conventional shielding gas flow on plume. The results show that the shielding gas has a very significant effect on the suppression of the slender part of the plume, and the greater the gas flow rate, the better the plume removal effect. The addition of the shielding gas makes the welding process more stable, the molten pool flows stably, and the frequency of spatter eruption is reduced. Under the experimental conditions, the optimal shielding gas flow rate is around 15 l/min, and the penetration depth and width are increased by about 10% and decreased by about 22%, respectively, compared with that without adding the shielding gas. Based on the gas flow simulation, the gas flow pressure (about 132 Pa) generated by an appropriate amount of shielding gas (about 15 l/min) can press the liquid column and spatter near the keyhole mouth into the molten pool to avoid the spatter eruption. Excessive shielding gas flow will interfere with the flow of the molten pool excessively, and the weld surface will show a serious undercut phenomenon. [ABSTRACT FROM AUTHOR]

Background Calcitonin gene-related peptide (CGRP), an immunomodulatory neuropeptide, is important for regulating pain transmission, vasodilation, and the inflammatory response. However, the molecular mechanisms of the CGRP-mediated immune response remain unknown. Methods The effects of CGRP on bacterial meningitis (BM) and its underlying mechanisms were investigated in BM mice in vivo and macrophages in vitro. Results Peripheral injection of CGRP attenuated cytokine storms and protected mice from fatal pneumococcal meningitis, marked by increased bacterial clearance, improved neuroethology, and reduced mortality. When the underlying mechanisms were investigated, we found that CGRP induces proteasome-dependent degradation of major histocompatibility complex class II (MHC-II) in macrophages and then inhibits CD4+ T-cell activation. MARCH1 was identified as an E3 ligase that can be induced by CGRP engagement and promote K48-linked ubiquitination and degradation of MHC-II in macrophages. These results provide new insights into neuropeptide CGRP-mediated immune regulation mechanisms. Conclusions We conclude that targeting the nervous system and manipulating neuroimmune communication is a promising strategy for treating intracranial infections like BM. [ABSTRACT FROM AUTHOR]

Background: Junctional adhesion molecule 2 (JAM2) plays a pivotal role in various biological processes, including proliferation, metastasis and angiogenesis, contributing to tumor progression. While previous studies have highlighted the polarizing functions of JAM2 in different cancer types, its specific role in lung adenocarcinoma (LUAD) remains unclear. Methods: In this study, we harnessed multiple public databases to analyze the expression and prognostic significance of JAM2 in LUAD. Using the Linkedomics database, Matescape database and R package, we explored the associated genes, the potential biological functions and the impact of JAM2 on the tumor microenvironment. Our findings from public databases were further validated using real‐time quantitative PCR, western blot and immunohistochemistry. Additionally, in vitro experiments were conducted to assess the influence of JAM2 on LUAD cell proliferation, invasion, migration, apoptosis and epithelial–mesenchymal transition. Furthermore, we established a xenograft model to investigate the in vivo effects of JAM2 on tumorigenesis. Results: Our results revealed a significant downregulation of JAM2 in LUAD, and patients with low JAM2 expression exhibited unfavorable overall survival outcomes. Functional enrichment analysis indicated that JAM2 may be associated with processes such as cell adhesion, extracellular matrix, cell junctions and regulation of proliferation. Notably, increased JAM2 expression correlated with higher tumor microenvironment scores and reduced immune cell abundance. Furthermore, overexpression of JAM2 induced apoptosis, suppressed tumor proliferation and exhibited potential inhibitory effects on tumor invasion and migration through the modulation of epithelial–mesenchymal transition. Additionally, in vivo experiments confirmed that JAM2 overexpression led to a reduction in tumor growth. Conclusion: Overall, our study highlights the clinical significance of low JAM2 expression as a predictor of poor prognosis in LUAD patients. Moreover, JAM2 was found to exert inhibitory effects on various aspects of tumor progression. Consequently, JAM2 emerges as a promising prognostic biomarker and a potential therapeutic target for LUAD patients. [ABSTRACT FROM AUTHOR]

Tescalcin (TESC) is a critical regulator of cell differentiation and growth, promoting malignant progression in various tumors. However, the role of TESC in esophageal squamous carcinoma (ESCC) remains unclear. Immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and western blot were utilized to identify the difference in TESC expression between ESCC tissues and normal tissues adjacent to the carcinoma. The relationship between TESC and several clinicopathological features was shown by the chi-square test. Log-rank analysis and Cox regression were used to detect the relationship between TESC and the prognosis in ESCC. Clone formation and cell count kit-8 (CCK-8) were applied to detect the impact of TESC on ESCC proliferation. Wound healing assay and transwell assay were used to confirm the influence of TESC on the invasion and migration. Spearman correlation coefficient was used to describe the correlation between TESC and epithelial-mesenchymal transition (EMT)-related protein expression in ESCC. Western blot was used to detect the effect of TESC on the expression of E-cadherin, N-cadherin, and Vimentin as well as AKT signaling pathway. Xenograft tumors were developed to test the pro-tumorigenic impacts of TESC in vivo. TESC was upregulated expression in ESCC tissues and was linked to poorer prognosis and worse tumor infiltration, TNM stage, and lymph node metastasis. Meanwhile, TESC was able to act as an independent prognostic factor in ESCC. TESC promoted tumor cell proliferation, invasion, migration, EMT progression, and activated the phosphorylation of the AKT pathway. Furthermore, TESC knockdown inhibited the growth of carcinoma in vivo. TESC is a predictive factor for poor prognosis in ESCC and may provide a new strategy for ESCC treatment. [ABSTRACT FROM AUTHOR]

Introduction: Excessive immune activation induces tissue damage during infection. Compared to external strategies to reconstruct immune homeostasis, host balancing ways remain largely unclear., Objectives: Here we found a neuroimmune way that prevents infection-induced tissue damage., Methods: By FACS and histopathology analysis of brain Streptococcus pneumonia meningitis infection model and behavioral testing. Western blot, co-immunoprecipitation, and ubiquitination analyze the Fluoxetine initiate 5-HT7R-STUB1-CCR5 K48-linked ubiquitination degradation., Results: Fluoxetine, a selective serotonin reuptake inhibitor, or the agonist of serotonin receptor 5-HT 7 R, protects mice from meningitis by inhibiting CCR5-mediated excessive immune response and tissue damage. Mechanistically, the Fluoxetine-5-HT 7 R axis induces proteasome-dependent degradation of CCR5 via mTOR signaling, and then recruits STUB1, an E3 ubiquitin ligase, to initiate K48-linked polyubiquitination of CCR5 at K138 and K322, promotes its proteasomal degradation. STUB1 deficiency blocks 5-HT 7 R-mediated CCR5 degradation., Conclusion: Our results reveal a neuroimmune pathway that balances anti-infection immunity via happiness neurotransmitter receptor and suggest the 5-HT 7 R-CCR5 axis as a potential target to promote neuroimmune resilience., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Objectives: To compare the clinical effect between two acupoint regimens of moxibustion on knee osteoarthritis (KOA), and observe the influences on the serum content of interleukin 1α (IL-1α), interleukin-17A (IL-17A), tumor necrosis factor α (TNF-α), bone gla protein (BGP) and osteoprotegerin (OPG)., Methods: KOA patients were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 3 cases dropped off). In the observation group, moxibustion was applied to Xiyan (EX-LE5), Dubi (ST35), Zusanli (ST36), Dazhu (BL11), Xuanzhong (GB39) and Yongquan (KI1) on the affected side. In the control group, EX-LE5, ST35 and ST36 were selected on the affected side. One session of treatment took 30 min in each group, delivered 3 times a week and the duration of treatment was 4 weeks. The scores of Western Ontario and McMaster University (WOMAC) and visual analogue scale (VAS) were observed and the serum content of IL-1α, IL-17A, TNF-α, BGP and OPG of the two groups were measured before and after treatment., Results: Compared with those before treatment, the WOMAC score, VAS score and the serum content of IL-1α, IL-17A and TNF-α were decreased ( P <0.05), and the content of BGP and OPG were increased ( P <0.05) after treatment. Compared with the control group, the WOMAC score, VAS score and the serum content of IL-1α and TNF-α in the observation group were lower ( P <0.05), and the content of BGP and OPG were higher ( P <0.05). The total effective rate of the observation group was 89.5% (34/38), and that of the control group was 83.8% (31/37), with no statistically significant difference., Conclusions: Moxibustion therapy of "nourishing the kidney and benefiting the marrow" can relieve joint pain, improve joint function, reduce the level of inflammatory factors and ameliorate bone metabolic indicators. The effect of the acupoint regimen in this moxibustion therapy is better than that of the local acupoint selection.