In this study, a deep learning algorithm based on the you-only-look-once (YOLO) approach is proposed for the quality inspection of printed circuit boards (PCBs). The high accuracy and efficiency of ...deep learning algorithms has resulted in their increased adoption in every field. Similarly, accurate detection of defects in PCBs by using deep learning algorithms, such as convolutional neural networks (CNNs), has garnered considerable attention. In the proposed method, highly skilled quality inspection engineers first use an interface to record and label defective PCBs. The data are then used to train a YOLO/CNN model to detect defects in PCBs. In this study, 11,000 images and a network of 24 convolutional layers and 2 fully connected layers were used. The proposed model achieved a defect detection accuracy of 98.79% in PCBs with a batch size of 32.
In many human cancers, including hepatocellular carcinoma (HCC), high density of infiltrating tumor-associated macrophages (TAM) is associated with poor prognosis. Most TAMs express a M2 phenotype ...subsequently supporting tumor growth. How tumor cells polarize these TAMs to a pro-tumor M2 phenotype is still poorly understood. Our previous studies have revealed that a Toll-like receptor 2 (TLR2)-dependent autophagy triggered by hepatoma-derived factors down-regulates NF-κB p65 and drives M2 macrophage differentiation. However, the underlying mechanisms and potential hepatoma-derived TLR2 ligands are not clear. Here, we provide evidence to reveal that NADPH oxidase 2 (NOX2)-dependent reactive oxygen species (ROS) generation is crucial for HCC-induced autophagy, NF-κB p65 down-regulation and M2 phenotype polarization in primary macrophages. This NOX2-generated ROS production in abolished in TLR2-deficient macrophages. HCC-derived or recombinant high-mobility group box 1 (HMGB1) is able to trigger this TLR2-mediated M2 macrophage polarization. Blockage of HMGB1 and ROS by inhibitors, ethyl pyruvate and N-acetylcysteine amide, respectively, significantly reduces both M2 macrophage accumulation and liver nodule formation in HCC-bearing mice. Our findings uncover a HMGB1/TLR2/NOX2/autophagy axis to trigger M2 macrophage polarization in HCC that can be considered as a novel therapeutic target for treating HCC.
Abstract
Objectives
We conducted this nationwide population-based study in Taiwan to investigate whether there is a bidirectional relationship between SLE and non-Hodgkin’s lymphoma (NHL).
Methods
...Using the National Health Insurance Research Database of Taiwan, we identified 16 417 patients with new-onset SLE without previous cancer and 25 069 patients with new-onset NHL without previous SLE as two non-overlapping cohorts from 1998–2012, and followed them until 2013. Standardized incidence ratio (SIR) for NHL in the patients with SLE and SIR for SLE in the patients with NHL were compared with the general population.
Results
Among the 16 417 patients with SLE, 512 developed cancers, including 34 with NHL. The highest SIR was that for NHL (SIR 4.2, 95% CI 2.9, 5.9) in site-specific cancer risk analysis. Among the 25 069 patients with NHL, 14 developed SLE, and the SIR was also increased (SIR 2.0, 95% CI 1.1, 3.4). The SIRs of the patients with SLE to develop NHL and the patients with NHL to develop SLE were both highest within the first year after the diagnosis of each disease.
Conclusion
This nationwide population-based study is the first study to report a bidirectional relationship between SLE and NHL. This finding may suggest being alert for the patients with SLE or NHL who have early sings of the other disease in clinical care.
Protocatechuic aldehyde (PCA) is a natural product that has various benefits for fibrosis.
This study evaluated the effects of PCA on renal fibrosis.
Epithelial-mesenchymal transition (EMT) was ...induced by 20 ng/mL transforming growth factor-β1 (TGF-β1), followed by treatment with 1 and 5 μM PCA, in the rat renal proximal tubular cell line NRK-52E. Cell viability, protein expression, and scratch wound-healing assays were conducted. Sprague-Dawley (SD) rats underwent unilateral ureteral obstruction (UUO) surgery for renal fibrosis indication and were treated with 50 and 100 mg/kg PCA for 14 days.
The IC
50
of PCA was appropriately 13.75 ± 1.91 μM in NRK-52E cells, and no significant difference at concentrations less than 5 μM. PCA ameliorated TGF-β1-induced EMT, such as enhanced E-cadherin and decreased vimentin. Fibrotic markers collagen IV and α-smooth muscle actin (α-SMA) increased in TGF-β1-induced NRK-52E. Moreover, PCA reduced TGF-β1-induced migration in the wound-healing assay. Analysis of rat kidneys indicated that PCA reduced UUO-induced hydronephrosis (control: 15.11 ± 1.00%; UUO: 39.89 ± 1.91%; UUO + PCA50: 18.37 ± 1.61%; UUO + PCA100: 17.67 ± 1.39%). Protein level demonstrated that PCA not only decreased vimentin expression and enhanced E-cadherin expression, but inhibited UUO-induced collagen IV and α-SMA upregulation, indicating that it could mitigate EMT in a rat model of UUO-induced renal fibrosis.
This study suggested that PCA decreases TGF-β1-induced fibrosis and EMT in vitro and in vivo. These findings demonstrate pharmacological effects of PCA and might be a potential strategy for the prevention of organ fibrosis in clinics.
Diabetic nephropathy (DN) is one of the most severe chronic kidney diseases in diabetes and is the main cause of end-stage renal disease (ESRD). Protocatechuic aldehyde (PCA) is a natural product ...with a variety of effects on pulmonary fibrosis. In this study, we examined the effects of PCA in C57BL/KS db/db male mice. Kidney morphology, renal function indicators, and Western blot, immunohistochemistry, and hematoxylin and eosin (H&E) staining data were analyzed. The results revealed that treatment with PCA could reduce diabetic-induced renal dysfunction, as indicated by the urine albumin-to-creatinine ratio (db/m: 120.1 ± 46.1μg/mg, db/db: 453.8 ± 78.7 µg/mg, db/db + 30 mg/kg PCA: 196.6 ± 52.9 µg/mg, db/db + 60 mg/kg PCA: 163.3 ± 24.6 μg/mg,
< 0.001). However, PCA did not decrease body weight, fasting plasma glucose, or food and water intake in db/db mice. H&E staining data revealed that PCA reduced glomerular size in db/db mice (db/m: 3506.3 ± 789.3 μm
, db/db: 6538.5 ± 1818.6 μm
, db/db + 30 mg/kg PCA: 4916.9 ± 1149.6 μm
, db/db + 60 mg/kg PCA: 4160.4 ± 1186.5 μm
< 0.001). Western blot and immunohistochemistry staining indicated that PCA restored the normal levels of diabetes-induced fibrosis markers, such as transforming growth factor-beta (TGF-β) and type IV collagen. Similar results were observed for epithelial-mesenchymal transition-related markers, including fibronectin, E-cadherin, and α-smooth muscle actin (α-SMA). PCA also decreased oxidative stress and inflammation in the kidney of db/db mice. This research provides a foundation for using PCA as an alternative therapy for DN in the future.
Innate immunity, armed with pattern recognition receptors including Toll-like receptors (TLR), is critical for immune cell activation and the connection to anti-microbial adaptive immunity. However, ...information regarding the impact of age on the innate immunity in response to SARS-CoV2 adenovirus vector vaccines and its association with specific immune responses remains scarce.
Fifteen subjects between 25-35 years (the young group) and five subjects between 60-70 years (the older adult group) were enrolled before ChAdOx1 nCoV-19 (AZD1222) vaccination. We determined activation markers and cytokine production of monocyte, natural killer (NK) cells and B cells
stimulated with TLR agonist (poly (I:C) for TLR3; LPS for TLR4; imiquimod for TLR7; CpG for TLR9) before vaccination and 3-5 days after each jab with flow cytometry. Anti-SARS-CoV2 neutralization antibody titers (surrogate virus neutralization tests, sVNTs) were measured using serum collected 2 months after the first jab and one month after full vaccination.
The older adult vaccinees had weaker vaccine-induced sVNTs than young vaccinees after 1
jab (47.2±19.3% vs. 21.2±22.2%,
value<0.05), but this difference became insignificant after the 2
jab. Imiquimod, LPS and CpG strongly induced CD86 expression in IgD
CD27
naïve and IgD
CD27
memory B cells in the young group. In contrast, only the IgD
CD27
naïve B cells responded to these TLR agonists in the older adult group. Imiquimode strongly induced the CD86 expression in CD14
monocytes in the young group but not in the older adult group. After vaccination, the young group had significantly higher IFN-γ expression in CD3
CD56
NK cells after the 1
jab, whilst the older adult group had significantly higher IFN-γ and granzyme B expression in CD56
NK cells after the 2
jab (all
value <0.05). The IFN-γ expression in CD56
and CD56
NK cells after the first vaccination and CD86 expression in CD14
monocyte and IgD
CD27
double-negative B cells after LPS and imiquimod stimulation correlated with vaccine-induced antibody responses.
The innate immune responses after the first vaccination correlated with the neutralizing antibody production. Older people may have defective innate immune responses by TLR stimulation and weak or delayed innate immune activation profile after vaccination compared with young people.
The role of redox regulation in immune‐mediated arthritis has been previously described. However, the relationship between innate immune cells, including innate lymphoid cells (ILCs) and ...phagocyte‐derived ROS, in this process remains unclear. Here, we characterize ILCs and measure the IL‐1 family cytokines along with other cytokines relevant to ILC functions and development in serum‐induced arthritic joints in wild type and phagocytic NADPH oxidase (NOX2)‐deficient Ncf1−/− mice. We found more severe serum‐induced joint inflammation and increased NCR+ ILC3s in inflamed joints of Ncf1−/− mice. Furthermore, in vitro stimulation with IL‐1β on Tbet+ ILC1s from joints facilitated their differentiation into ROR‐γt+ ILC3s. Moreover, treatment with IL‐1 antagonists effectively lowered the proportions of NCR+ ILC3s and IL‐17A producing ILC3s in Ncf1−/− arthritic mice and ameliorated the joint inflammation. These results suggest that NOX2 is an essential regulator of ILC transdifferentiation and may mediate this process in a redox‐dependent manner through IL‐1β production in the inflammatory joint. Our findings shed important light on the role of ILCs in the initiation and progression in tissue inflammation and delineate a novel innate immune cell‐mediated pathogenic mechanism through which redox regulation may determine the direction of immune responses in joints.
Innate lymphoid cells (ILCs) and cytokines were investigated in mice with different ROS production levels to reveal the immunopathogenesis of arthritis. The differentiation to NCR+ ILC3s induced by IL‐1β in joints with lower ROS may aggravate arthritis. This study highlights the redox‐IL1β axis as a target for arthritis treatment.
Although sporadic case reports have demonstrated successful management of eosinophilic granulomatosis with polyangiitis (EGPA) by anti-IL-5 therapy, larger-scale monocentric studies for the efficacy ...of mepolizumab (MEP), an IL-5 monoclonal antibody, are still lacking in Taiwan.
Hospitalized EGPA patients aged at least 18 years were enrolled from November 1998 to October 2023, and analyzed for demographic, clinical, laboratory, medication and outcome data, focusing on the efficacy and safety of biologics use, particularly induction therapy with MEP.
Twenty-seven EGPA patients aged 10–70 years (43 ± 15) at disease diagnosis were recruited with 21 under combined corticosteroids/cyclophosphamide induction therapy. Seventeen patients received biologics with 13 under MEP therapy. Ten patients aged 19–71 years (48 ± 15) completed 12-month induction therapy with a 100 mg quadri-weekly subcutaneous injection regimen indicated for active or relapse disease. There were reduced BVAS with complete remission in 6 and partial remission in 4 patients, lower CRP levels, decreased eosinophil counts with an inhibition of 92∼96 %, and tapered prednisolone dosages from 5 to 25 (13.0 ± 6.3) to 0–10 (3.3 ± 3.1) mg/day. Only one patient had an adverse event of injection site reactions. Nine patients received the same regimen for annual maintenance therapy. All had a persistent clinical remission. In these patients, 13–56 injections (41 ± 15) were prescribed with a follow-up period of 12∼52 months (38 ± 14).
In this retrospective study, induction therapy with a 12-month 100 mg MEP quadri-weekly subcutaneous injection regimen demonstrates the efficacy and safety for active and relapsing EGPA patients.
Reactive oxygen species (ROS) are produced by host phagocytes and play an important role in antimicrobial actions against various pathogens. Autoimmune uveitis causes blindness and severe visual ...impairment in humans at all ages worldwide. However, the role of ROS in autoimmune uveitis remains unclear. We used ROS-deficient (
) mice to investigate the role of ROS in experimental autoimmune uveitis (EAU). Besides, we also used the antioxidant N-acetylcysteine (NAC) treatment to evaluate the effect of suppression of ROS on EAU in mice. The EAU disease scores of
mice were significantly lower than those of wild-type mice. EAU induction increased the levels of cytokines (interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-12, IL-17, and tumor necrosis factor (TNF)-α) and chemokines (monocyte chemoattractant protein (MCP)-1) in the retinas of wild-type mice but not in those of
mice. EAU induction enhanced the level of NF-κB activity in wild-type mice. However, the level of NF-κB activity in
mice with EAU induction was low. Treatment with the antioxidant NAC also decreased the severity of EAU in mice with reduced levels of oxidative stress, inflammatory mediators, and NF-κB activation in the retina. We successfully revealed a novel role of ROS in the pathogenesis of EAU and suggest a potential antioxidant role for the treatment of autoimmune uveitis in the future.
Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 ...(NOX2)-deficient mice (Ncf1-/-) to investigate the role of leukocyte-produced reactive oxygen species (ROS) in mycobacterium-induced granulomatous inflammation. We found poorly controlled mycobacterial proliferation, significant body weight loss, and a high mortality rate after M. marinum infection in Ncf1-/- mice. Moreover, we noticed loose and neutrophilic granulomas and higher levels of interleukin (IL)-1β and neutrophil chemokines in Ncf1-/- mice when compared with those in wild type mice. The lack of ROS led to reduced production of IL-1β in macrophages, whereas neutrophil elastase (NE), an abundant product of neutrophils, may potentially exert increased inflammasome-independent protease activity and lead to higher IL-1β production. Moreover, we showed that the abundant NE and IL-1β were present in the caseous granulomatous inflammation of human TB infection. Importantly, blocking of IL-1β with either a specific antibody or a recombinant IL-1 receptor ameliorated the pulmonary inflammation. These findings revealed a novel role of ROS in the early pathogenesis of neutrophilic granulomatous inflammation and suggested a potential role of IL-1 blocking in the treatment of mycobacterial infection in the lung.
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