Enhancing the efficacy of synthesising PHA from nitrogen-limited activated sludge using magnetic field.

Polyhydroxyalkanes (PHA) is a biodegradable biopolyester. In this study, we introduced the biological effects of magnetic field into a sequencing batch reactor (SBR) for PHA production to evaluate the effect of different strength of magnetic field on the efficacy of PHA synthesis by activated sludge and used the magnetic field to enhance the PHA synthesis capacity of nitrogen-limited activated sludge and to optimise the percentage of the content of the two monomers in PHA. The results showed that the magnetic field of appropriate strength was favourable to increase the production of PHA and to increase the percentage of PHV. In addition, microbial community analysis showed that there was an obvious succession of key functional bacteria under different strength of magnetic field. The highest PHA accumulation was achieved after the magnetic field of 16 mT, which reached 57.65% of the dry weight of sludge. In addition, the PHV monomers were more sensitive to the response of the magnetic field, and the magnetic field of 8mT and 16mT positively promoted the synthesis of PHV. It is worth noting that too high a magnetic field would have an inhibitory effect on the synthesis of PHA.

Prevalence and clinical markers of herpes simplex virus infection in oral lesions of bullous pemphigoid.

Background: The manifestations of bullous pemphigoid (BP) and herpes simplex virus (HSV) infection are similar in oral mucosa, and the laboratory detection of HSV has some limitations, making it difficult to identify the HSV infection in oral lesions of BP. In addition, the treatments for BP and HSV infection have contradictory aspects. Thus, it is important to identify the HSV infection in BP patients in time. Objective: To identify the prevalence and clinical markers of HSV infection in oral lesions of BP. Methods: This prospective cross-sectional descriptive analytical study was conducted on 42 BP patients with oral lesions. A total of 32 BP patients without oral lesions and 41 healthy individuals were enrolled as control groups. Polymerase chain reaction was used to detect HSV. Clinical and laboratory characteristics of patients with HSV infection were compared with those without infection. Results: A total of 19 (45.2%) BP patients with oral lesions, none (0.0%) BP patients without oral lesions, and four (9.8%) healthy individuals were positive for HSV on oral mucosa. Among BP patients with oral lesions, the inconsistent activity between oral and skin lesions (p=0.001), absence of blister/blood blister in oral lesions (p=0.020), and pain for oral lesions (p=0.014) were more often seen in HSV-positive than HSV-negative BP patients; the dosage of glucocorticoid (p=0.023) and the accumulated glucocorticoid dosage in the last 2 weeks (2-week AGC dosage) (p=0.018) were higher in HSV-positive BP patients. Combining the above five variables as test variable, the AUC was 0.898 (p<0.001) with HSV infection as state variable in ROC analysis. The absence of blister/blood blister in oral lesions (p=0.030) and pain for oral lesions (p=0.038) were found to be independent predictors of HSV infection in multivariable analysis. A total of 14 (73.7%) HSV-positive BP patients were treated with 2-week famciclovir and the oral mucosa BPDAI scores significantly decreased (p<0.001). Conclusion: HSV infection is common in BP oral lesions. The inconsistent activity between oral and skin lesions, absence of blister in oral lesions, pain for oral lesions, higher currently used glucocorticoid dosage, and higher 2-week AGC dosage in BP patients should alert physicians to HSV infection in oral lesions and treat them with 2-week famciclovir in time.

Evaluation of Dupilumab in Patients With Bullous Pemphigoid.

Importance: Dupilumab is a theoretically novel therapy for bullous pemphigoid (BP). However, its effectiveness and safety have yet to be confirmed in a large-scale study. Objective: To assess the efficacy and safety of dupilumab in patients with BP and evaluate factors that potentially affect short-term and long-term outcomes. Design, Setting, and Participants: A retrospective cohort study was conducted from January 1, 2021, to July 31, 2022. The median (IQR) follow-up period was 24.6 (11.5-38.4) weeks. This multicenter study was performed in 6 dermatology departments of the National Autoimmune Bullous Diseases Cooperative Group of China. Adult patients with BP that received 300 mg of dupilumab every 2 weeks following an initial dose of 600 mg were included. Patients were eligible if they had a clinical presentation of BP combined with immunological or pathological evidence. Patients with drug-induced BP, with less than 4 weeks of follow-up, and who received dupilumab or any other biologics within 6 months were excluded. Main Outcomes and Measures: The primary outcome was the proportion of patients who achieved disease control within 4 weeks. Disease control was defined as the absence of new lesions and pruritus, combined with the healing of existing lesions. Complete remission rates, relapse rates, changes in Bullous Pemphigoid Disease Area Index (BPDAI) scores, itching numerical rating scale (NRS) scores, laboratory results within 64 weeks, and adverse events (AEs) were also assessed. Results: Among 146 patients (median [IQR] age, 73 [64-85] years; 86 [58.9%] male patients) included in the study, 127 (87.0%) patients achieved disease control within 4 weeks, with a median (IQR) time of 14 (7-14) days. A total of 52 (35.6%) patients achieved complete remission, and 13 (8.9%) patients relapsed during the observation period. The complete remission rate and cumulative relapse rate at week 64 were 62.5% (5 of 8) and 30.9%, respectively. There was rapid and sustained improvement in clinical indicators and laboratory examination results after dupilumab treatment, including BPDAI scores, itching NRS scores, serum anti-BP180 and anti-BP230 antibodies, total IgE levels, and eosinophil count. Of these 146 patients, 107 (73.3%) did not report any AEs. The most common AEs were infections and eosinophilia. Serum anti-BP180 antibody levels of greater than 50 relative units (RU)/mL (OR, 3.63; 95% CI, 0.97-12.61; P = .045) were associated with 4-week disease control, and male patients were more likely to relapse (HR, 10.97; 95% CI, 1.42-84.92; P = .02). Conclusions and Relevance: In this retrospective cohort study, dupilumab treatment was associated with improved clinical symptoms in patients with BP. The safety profile was favorable, although concurrent infection and eosinophilia might pose potential concerns. This study suggests that patients with anti-BP180 antibody levels of at least 50 RU/mL and female sex may respond better.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio are positively correlated with disease activity of bullous pemphigoid.

Bullous pemphigoid (BP) is a complex inflammatory process with elevated levels of autoantibodies, eosinophils, neutrophils, and various cytokines. Hematological inflammatory biomarkers can reflect inflammatory state in various diseases. Up to now, the correlations of hematological inflammatory biomarkers and disease activity of BP remain unknown. The purpose of this study was to clarify the associations between hematological inflammatory biomarkers and disease activity of BP. The levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR) and mean platelet volume (MPV) of 36 untreated BP patients and 45 age and gender matched healthy controls were detected by routine blood tests. The correlations between hematological inflammatory markers and clinical characteristics of BP were statistically analyzed. The Bullous Pemphigoid Disease Area Index (BPDAI) was used to measure disease activity of BP. The mean levels of NLR, PLR, PNR and MPV in 36 untreated BP patients were 3.9, 157.9, 45.7 and 9.4 fl, respectively. Increased NLR (p < 0.001), PLR (p < 0.01), and MPV (p < 0.001) but decreased PNR (p < 0.001) were observed in BP patients when compared with healthy controls. In BP patients, the levels of NLR were positively correlated to BPDAI Erosion/Blister Scores (p < 0.01); and the levels of NLR and PLR were both positively correlated to BPDAI without Damage Score (both p < 0.05) and BPDAI Total Score (both p < 0.05). No correlation was found in other statistical analyses between hematological inflammatory markers and clinical characteristics in BP patients involved in the present study. Therefore, NLR and PLR are positively correlated with disease activity of BP.

IgE anti-BP180 NC16A autoantibody in both serum and blister fluid samples does not correlate with disease activity of bullous pemphigoid.

The correlation between IgE anti-BP180 NC16A autoantibody and disease activity of bullous pemphigoid (BP) remains disputable. To determine the levels of IgE anti-BP180 NC16A autoantibody and its clinical significance in untreated BP patients. IgG and IgE anti-BP180 NC16A autoantibody in serum and blister fluid samples of 34 untreated BP patients was detected by enzyme-linked immunosorbent assay (ELISA), and correlation with clinical and pathological features of BP were statistically analysed. The Bullous Pemphigoid Disease Area Index (BPDAI) was used to measure disease activity of BP. The mean baseline level of IgG anti-BP180 NC16A autoantibody in serum and blister fluid samples of untreated BP patients was 75.3 U/mL and 1.54 U/mL, respectively (A450, cutoff: 0.126). IgE anti-BP180 NC16A autoantibody was positive in 21.9% serum and 14.7% blister fluid samples of untreated BP patients. IgE anti-BP180 NC16A autoantibody levels in serum samples positively correlated with those from blister fluid samples (r = 0.983, p < 0.05). However, IgE anti-BP180 NC16A autoantibody level in both serum and blister fluid samples of untreated BP patients did not correlate with IgG anti-BP180 NC16A autoantibody, age, extent of elevated peripheral blood eosinophils, BPDAI erosion/blister score, BPDAI urticaria/erythema score, BPDAI pruritus score, BPDAI without damage score, or BPDAI total score (all p > 0.05). No significant correlation was identified between disease activity and positive or negative anti-BP180 NC16A IgE autoantibody. Conclusion: IgE anti-BP180 NC16A autoantibody in both serum and blister fluid samples does not appear to correlate with disease activity of BP.

Association of Alopecia Areata with Vitamin D and Calcium Levels: A Systematic Review and Meta-analysis.

INTRODUCTION: To investigate the associations of alopecia areata (AA) with serum vitamin D and calcium levels. METHODS: A systematic review of all relevant articles published up to February 2020 in PubMed, Embase, and Cochrane Library databases was conducted. Primary endpoints were serum 25-hydroxyvitamin D [25(OH)D] levels and vitamin D deficiency, and the secondary endpoint was serum calcium level. Odds ratio (OR) and standardized mean difference (SMD) with 95% CI across studies were analyzed. RESULTS: Data on 1585 patients with AA and 1114 controls from 16 case-control studies and three cross-sectional studies were included in this meta-analysis. A pooled meta-analysis was conducted using the random-effects model because of inter-study heterogeneity (vitamin D level, I2 = 87.90%; vitamin D deficiency, I2 = 81.10%; serum calcium level, I2 = 83.80%). A combined analysis revealed that patients with AA had significantly lower mean serum 25(OH)D level compared with control (WMD - 9.08, 95% CI - 11.65, - 6.50, p < 0.001), and were more likely to have vitamin D deficiency (OR 4.14, 95% CI 2.34, 7.35, p < 0.001). However, the pooled analysis revealed that patients with AA did not have significantly lower serum calcium levels compared with control (WMD - 0.17, 95% CI - 0.40, 0.06, p = 0.143). Subgroup analysis suggested that matched control, mean age, and country might contribute to the heterogeneity of serum vitamin D level, while study design, matched control, and country might contribute to the heterogeneity of vitamin D deficiency. CONCLUSION: Deficiency of serum 25(OH)D level, rather than calcium level, was present in patients with AA. Screening for vitamin D deficiency and vitamin D supplementation may be beneficial in the treatment of patients with AA.

[Expression of MMP-2 and TIMP-1 in renal tissues of patients with chronic active antibody-mediated renal graft rejection].

OBJECTIVE: To investigate the expressions of matrix metalloprotein-2 (MMP-2) and tissue inhibitor of metallopeptidase inhibitor-1 (TIMP-1) in the renal allografts of patients with chronic active antibody-mediated rejection (ABMR), and explore their role in the pathogenesis of ABMR. METHODS: Immunohistochemistry and computer-assisted image analysis were used to detect the expression of MMP-2 and TIMP-1 in the renal allografts of 46 patients with interstitial fibrosis and tubular atrophy (IF/TA), with 15 normal renal tissue specimens as the control. The association of MMP-2 and TIMP-1 with the pathological grade of IF/TA in ABMR was analyzed. RESULTS: The expressions of MMP-2 and TIMP-1 significantly increased in the renal tissues of the patients as compared with the normal renal tissues (P<0.05). MMP-2 expression tended to decrease, while TIMP-1 and serum creatinine increased with the pathological grades of IF/TA (P<0.05). In IF/TA group, the expression of TIMP-1 was positively correlated to serum creatinine level (r=0.718, P=0.00<0.05). CONCLUSION: Abnormal expressions of MMP-2 and TIMP-1 can promote the development of renal fibrosis in chronic ABMR.

Organic field-effect transistors containing a SiO2 nanoparticle thin film as the gate dielectric.

In this article, we report the fabrication of organic field-effect transistors using self-assembled SiO2 as a gate dielectric material and pentacene as a semiconductor. The dielectric layer was self-assembled with 10 layers of SiO2 nanoparticles 45 nm in diameter, and its breakdown field was larger than 0.57 MV/cm. Being a low-cost and low-temperature process, the layer-by-layer self-assembly is particularly suitable for organic field-effect transistor fabrication. The pentacene was thermally evaporated on the substrate under high vacuum at the room temperature. The fabricated transistor has a threshold voltage of 0.3 V, field-effect mobility of 0.05 cm2/Vs, and slope of 1.4 V/decade.