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Bubble cap structures are researched for the particle erosion wear of the distribution plate (tray for short) in an S Zorb desulfurization reactor. The semi-empirical model of erosion wear prediction of gas–solid two-phase flow is revised by means of erosion wear experiments at high temperature and high speed. According to the revised erosion wear, the influence of the h0 (the distance from the bottom of the bubble cap to the tray), h1 (distance from the outlet of the lifting pipe to the top of the bubble cap interface), N (the number of cavities), d0 (the inner diameter of bubble cap) on erosion wear of trays are studied. The results show that a smaller h0 will make the erosion degree of the tray more serious; it is recommended to keep h0 = 17 mm. A larger h1 will alleviate the erosion wear degree of adsorbent particles on the tray, but considering the efficiency of the reaction, h1 = 36 mm is more appropriate. The increase of N reduces the erosion wear less but enhances the fluid disturbance and makes the erosion wear area unstable; so, N should be kept at 10. The increase of d0 reduces the velocity and density of fluid impacting the tray, thus reducing the erosion wear degree, which is an effective means. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory skin disease. The Wnt/β-catenin signaling pathway is essential for the regulation of adult stem cells, homeostasis, and tissue regeneration; however, the relationship between this pathway and interleukin (IL)-36γ in the pathogenesis of psoriasis remains unclear., Methods: In this study, psoriasiform model mice were established using imiquimod (IMQ) induction. Hematoxylin and eosin (H&E) staining was used to evaluate pathological morphologies, while immunohistochemistry was used to verify the expression patterns of β-catenin and the inflammatory factors IL-6, IL-17 A, and interferon (IFN)-γ., Results: IL-36γ treatment increased psoriasis area and severity index scores, and enhanced proliferation of keratinocytes in IMQ-induced psoriatic mice. The effects of IL-36γ on the severity of psoriasiform lesions and epidermal hyperplasia were partly inhibited by IWR-1, which is an inhibitor of the Wnt/β-catenin signaling pathway. Furthermore, the levels of proinflammatory cytokines and molecules involved in the Wnt/β-catenin signaling pathway in psoriatic mouse skin, including IL-6, IL-17 A, IFN-γ, β-catenin, and Dickkopf-1 (DKK1), were upregulated by treatment with IL-36γ. Consistently, the effects of IL-36γ on the inflammatory response and the Wnt/β-catenin signaling pathway were alleviated by IWR-1., Conclusions: Taken together, our findings suggested that inhibition of the Wnt/β-catenin signaling pathway may be useful in the alleviation of IL-36γ-induced psoriasis-like lesions., Competing Interests: Declarations. Ethical approval and consent to participate: This study protocols were approved by Animal Ethics committee of Peking Union Medical College Hospital. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond poorly to immune checkpoint inhibitors (ICIs). It has been reported that the number of CD8 + T cells is reduced in EGFR-mutated NSCLC. However, the extent of heterogeneity and effector function of distinct populations of CD8 + T cells has not been investigated intensively. In addition, studies investigating whether a combination of radiotherapy and ICIs can improve the efficacy of ICIs in EGFR-mutated lung cancer are lacking. Single-cell RNA sequencing (scRNA-seq) was used to investigate the heterogeneity of CD8 + T cell populations in EGFR-mutated NSCLC. The STING pathway was explored after hypofractionated radiation of EGFR-mutated and wild-type cells. Mice bearing LLC-19del and LLC-EGFR tumors were treated with radiotherapy plus anti-PD-L1. The scRNA-seq data showed the percentage of progenitor exhausted CD8 + T cells was lower in EGFR-mutated NSCLC. In addition, CD8 + T cells in EGFR-mutated NSCLC were enriched in oxidative phosphorylation. In EGFR-mutated and wild-type cells, 8 Gy × 3 increased the expression of chemokines that recruit T cells and activate the cGAS-STING pathway. In the LLC-19del and LLC-EGFR mouse model, the combination of radiation and anti-PD-L1 significantly inhibited the growth of abscopal tumors. The enhanced abscopal effect was associated with systemic CD8 + T cell infiltration. This study provided an intensive understanding of the heterogeneity and effector functions of CD8 + T cells in EGFR-mutated NSCLC. We showed that the combination of hypofractionated radiation and anti-PD-L1 significantly enhanced the abscopal responses in both EGFR-mutated and wild-type lung cancer by activating CD8 + T cells in mice., 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 © 2024. Published by Elsevier Inc.)

We aimed to analyze the clinical profile and malignancy indicators in dermatomyositis (DM) with anti-transcriptional intermediary factor 1 antibody (anti-TIF1γ-Ab). A comparison was made between clinical information of anti-TIF1γ DM patients with and without malignancy. Additionally, a review of the literature on anti-TIF1γ DM and malignancy was conducted by searching PubMed and EMBASE databases. In our cohort of 37 patients, 27.0% (10/37) developed malignancy. The timeframe during which these 10 patients developed malignancy ranged from 21 months prior to the diagnosis of DM to 36 months following the diagnosis of DM. Specifically, one patient was diagnosed with breast cancer at the age of 36. Comparing the groups with and without malignancy, we found that age over 65 years (40% vs 7.4%, P = 0.035), a shorter duration from the onset of symptoms to the diagnosis of DM (2.5 vs 10 months, P = 0.003), and higher erythrocyte sedimentation rate (ESR) levels (23 vs 10 mm/h, P = 0.048) were found to be associated with an increased risk of malignancy. Conversely, the presence of Gottron's papules (63% vs 20%, P = 0.029) may suggest a lower likelihood of malignancy. The literature review revealed that the prevalence of myositis-associated malignancy was 40.7% (340/836), with variations ranging from 19% to 82.9% across different series. In summary, factors such as age over 65 years, a shorter duration between symptom onset and diagnosis of DM, and elevated ESR levels may indicate an increased risk of malignancy in anti-TIF1γ DM patients., (© 2024 Japanese Dermatological Association.)

Introduction: Immune-related epidermal necrolysis (irEN), including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), represents a potentially lethal reaction to immune checkpoint inhibitors. An optimal treatment strategy remains undefined. This study evaluates the effectiveness and safety of combination therapy with corticosteroids and tumor necrosis factor inhibitors (TNFi) in treating irEN patients., Methods: In this single-center, prospective, observational study, patients with irEN received either corticosteroid monotherapy or a combination therapy of corticosteroids and TNFi (etanercept for SJS, infliximab for TEN). The primary endpoint was re-epithelization time, with secondary endpoints including corticosteroid exposure, major adverse event incidence, acute mortality rates, and biomarkers indicating disease activity and prognosis. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100051052)., Results: Thirty-two patients were enrolled (21 SJS, 11 TEN); 14 received combination therapy and 18 received corticosteroid monotherapy. IrEN typically occurred after 1 cycle of ICI administration, with a median latency of 16 days. Despite higher SCORTEN scores in the combination group (3 vs. 2, p = 0.008), these patients experienced faster re-epithelization (14 vs. 21 days; p < 0.001), shorter corticosteroid treatment duration (22 vs. 32 days; p = 0.005), and lower prednisone cumulative dose (1177 mg vs. 1594 mg; p = 0.073). Major adverse event rates were similar between groups. Three deaths occurred due to lung infection or disseminated intravascular coagulation, with mortality rates for both groups lower than predicted. Potential risk factors for increased mortality included continuous reduction in lymphocyte subset counts (CD4 + T cells, CD8 + T cells, natural killer cells) and consistent rises in inflammatory markers (serum ferritin, interleukin-6, TNF-α). Re-epithelization time negatively correlated with body mass index and positively correlated with epidermal detachment area and serum levels of interleukin-6 and TNF-α., Conclusions: Corticosteroids combined with TNFi markedly promote re-epithelization, reduce corticosteroid use, and decrease acute mortality in irEN patients without increasing major adverse events, offering a superior alternative to corticosteroid monotherapy. Inflammatory markers and lymphocyte subsets are valuable for assessing disease activity and prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Guo, Qu and Jin.)

Background: Palmoplantar pustulosis (PPP) is a chronic inflammatory disease of ill-defined etiopathology. Recent studies have proposed complete blood count-based hematological parameters, such as neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR), as biomarkers to monitor disease status in many inflammatory diseases. This study aimed to analyze for the first time the clinical significance of hematological parameters, including NLR, monocyte/lymphocyte ratio (MLR), PLR, mean platelet volume (MPV), plateletcrit (PCT), and pan-immune-inflammation value (PIV) in PPP patients., Methods: We retrospectively investigated the clinical and laboratory data of 237 patients with PPP and 250 sex-age-matched healthy controls (HCs). Hematological parameters were compared between patients with PPP and HCs. The correlations between these parameters and disease severity, as well as treatment response, were analyzed., Results: NLR, MLR, MPV, PCT, and PIV values were significantly higher in PPP patients than in HCs. But in receiver-operating characteristic analyses, only monocyte count (Youden Index = 0.53), PCT (Youden Index = 0.65), and PIV (Youden Index = 0.52) performed relatively accurate distinguishment between moderate-to-severe cases and mild cases. PCT and PIV values were significantly correlated with disease severity. After treatment, both PIV and PCT values decreased significantly in the responder group but not in the non-responder group., Conclusions: Hematological parameters altered significantly in PPP patients. PCT and PIV can be used as simple and inexpensive biomarkers for systemic inflammation in PPP patients., (© 2024 the International Society of Dermatology.)

Erythrodermic psoriasis (EP) is a rare and life-threatening disease, the pathogenesis of which remains to be largely unknown. Metabolomics analysis can provide global information on disease pathophysiology, candidate biomarkers, and potential intervention strategies. To gain a better understanding of the mechanisms of EP and explore the serum metabolic signature of EP, we conducted an untargeted metabolomics analysis from 20 EP patients and 20 healthy controls. Furthermore, targeted metabolomics for focused metabolites were identified in the serum samples of 30 EP patients and 30 psoriasis vulgaris (PsV) patients. In the untargeted analysis, a total of 2992 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed significant difference between groups. After screening, 98 metabolites were found to be significantly dysregulated in EP, including 67 down-regulated and 31 up-regulated. EP patients had lower levels of L-tryptophan, L-isoleucine, retinol, lysophosphatidylcholine (LPC), and higher levels of betaine and uric acid. KEGG analysis showed differential metabolites were enriched in amino acid metabolism and glycerophospholipid metabolism. The targeted metabolomics showed lower L-tryptophan in EP than PsV with significant difference and L-tryptophan levels were negatively correlated with the PASI scores. The serum metabolic signature of EP was discovered. Amino acid and glycerophospholipid metabolism were dysregulated in EP. The metabolite differences provide clues for pathogenesis of EP and they may provide insights for therapeutic interventions., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The necessity for tuberculosis preventive treatment (TPT) and routine T-SPOT.TB monitoring in patients with psoriasis and tuberculosis infection (TBI) undergoing interleukin (IL)-17A inhibitor therapy remains uncertain. This study aims to evaluate the long-term safety of IL-17A inhibitors administered without TPT and analyze changes in T-SPOT.TB among these patients. It also identifies risk factors for TBI in patients with psoriasis., Methods: This single-center prospective study enrolled adult patients with plaque psoriasis and TBI receiving IL-17A inhibitors. TBI was defined as positive T-SPOT.TB results (≥ 6 spots) without symptoms or evidence of active tuberculosis (ATB). TPT administration was based on contraindications, tuberculosis risk factors, and patient preferences. The primary endpoint was the incidence of ATB over 2 years. Secondary outcomes included T-SPOT.TB changes and TBI risk factors., Results: Of the 129 patients with psoriasis and TBI enrolled in the study, 97 (75.2%) did not receive TPT, while 32 (24.8%) did. Among them, 109 patients (84.5%) completed the 2-year follow-up. During the 235 person-years of observation, no ATB cases were identified. Median T-SPOT.TB values showed no significant changes from baseline to year 2 in both the non-TPT (20 vs. 17 spots, p = 0.975) and TPT groups (55 vs. 58 spots, p = 0.830). T-SPOT.TB reversed in 14 patients (12.8%), mostly in the non-TPT group. Moreover, for TBI risk factor analysis, a cohort of 212 patients with psoriasis with negative baseline T-SPOT.TB was evaluated, revealing a TBI prevalence of 37.8%. Logistic regression analysis highlighted age ≥ 45 years (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.50-3.99, p < 0.001) and body mass index (BMI) < 24.0 kg/m 2 (OR 2.12, 95% CI 1.27-3.54, p = 0.004) as independent risk factors for TBI., Conclusion: IL-17A inhibitors do not appear to reactivate tuberculosis in patients with psoriasis and TBI, potentially reducing the need for routine TBI screening and preventive treatment., Trial Registration: Chinese Clinical Trial Registry, ChiCTR2100045823., (© 2024. The Author(s).)

Objective: To examine the efficacy and safety of telitacicept in the treatment of patients with SLE in everyday clinical practice., Methods: Seventy-two patients with active SLE who received telitacicept for more than 24 weeks at multiple centres in China between 2019 and 2022 were retrospectively identified. Twenty-one of these patients received 52 continuous weeks of treatment with telitacicept. Treatment outcomes were analysed separately according to whether patients had renal or haematological abnormalities. Trajectory analysis was performed to identify patients with a limited response. Factors contributing to a limited response were explored by multivariable logistic regression analysis., Results: After treatment with telitacicept for 4, 12, 24 and 52 weeks, 22.22%, 54.17%, 72.22% and 80.95% of patients, respectively, achieved an SLE Responder Index 4; 8.33%, 26.39%, 34.72% and 47.62% achieved a Lupus Low Disease Activity State; and 0%, 4.17%, 8.33% and 23.81% achieved remission. Significant decreases in serum IgA, IgG and IgM levels were observed at 4 weeks and showed a downward trend at 12, 24 and 52 weeks. The median 24-hour urinary protein declined from 1323.5 mg to 224.0 mg in patients with lupus nephritis after treatment with telitacicept for 52 weeks. Furthermore, a large proportion of patients (10 of 13) with haematological abnormalities recovered after 52 weeks of treatment with telitacicept. No severe adverse events were reported during the observation period. Age appeared to have a negative impact on treatment efficacy., Conclusions: Telitacicept demonstrated favourable efficacy and safety in patients with active SLE and improved the renal and haematological manifestations of the disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: Pustular psoriasis is a chronic and recurrent autoimmune disease, although little is known about the disease burden of pustular psoriasis in China. We analyzed the characteristics and disease burdens of patients from Beijing who had generalized pustular psoriasis (GPP) or palmoplantar pustulosis (PPP)., Methods: This multicenter retrospective cohort study used a regional electronic health database that covered 30 public hospitals in Beijing. From June 2016 to June 2021, all patients with a diagnosis of GPP, PPP, or psoriasis vulgaris (PV) were identified by International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. The GPP and PPP cohorts were separately matched with patients with PV in a 3:1 ratio for comparisons. Demographic data, clinical characteristics, healthcare resource utilization, and costs were collected. Descriptive and comparative analyses were used to compare the cohorts., Results: There were 744 patients with GPP (46.8% men; age 42.14 ± 21.47 years) and 4808 patients with PPP (35.5% men; age 51.65 ± 16.12 years); 14.5% of patients with GPP had concomitant PV and 7.5% of patients with PPP had concomitant PV. Relative to matched patients with PV, patients with GPP had a higher prevalence of erythrodermic psoriasis (5.9% vs 0.4%, p < 0.0001), psoriatic arthritis (3.1% vs 1.5%, p = 0.007), and organ failure (1.1% vs 0.2%, p = 0.002). Relative to matched patients with PV, patients with PPP had a higher prevalence of cerebrovascular disease (4.7% vs 1.2%, p < 0.0001), thyroid dysfunction (3.9% vs 3.3%, p = 0.035), and type 2 diabetes mellitus (6.8% vs 5.9%, p = 0.030). More patients with GPP than patients with PV received systemic non-biological agents (27.9% vs 3.3%, p < 0.0001) and biologic agents (4.8% vs 2.0%, p = 0.010). More patients with PPP than patients with PV received topical agents (50.9% vs 34.7%, p < 0.0001) and systemic non-biological agents (17.8% vs 2.7%, p < 0.0001). More patients with GPP than patients with PV required inpatient hospitalization (22.0% vs 7.8%, p < 0.0001). Hospitalization stay was longer in patients with GPP than patients with PV (11.72 ± 0.45 vs 10.38 ± 0.45 days, p = 0.022). More patients with PPP than patients with PV had emergency visits (16.3% vs 12.8%, p < 0.0001). The GPP and PPP cohorts and their matched PV cohorts had no significant differences in costs. However, patients with PPP had lower outpatient costs than patients with PV (368.20 ± 8.19 vs 445.38 ± 5.90 Chinese Yuan per patient per month, p < 0.0001)., Conclusions: Patients from Beijing with GPP and PPP had higher disease burdens than matched PV cohorts, including the prevalence of comorbidities, healthcare resource utilization, and medication burden. However, the economic burden of pustular psoriasis was similar to that of PV. Practical and specific therapies are needed to reduce the burdens of pustular psoriasis., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Immune-mediated dermatoses are the skin diseases caused by the breakdown of immune tolerance,including lupus erythematosus and dermatomyositis.The imbalance between regulatory T cells (Tregs) and effector T cells (Teffs) plays a key role in the pathogenesis of these diseases.Low-dose interleukin-2 can preferentially activate Tregs and reverse the imbalance between Tregs and Teffs to recover the immune tolerance,which has attracted attention in the treatment of immune-mediated dermatoses.This review summarizes the research progress in the immunomodulatory mechanism and clinical application of low-dose interleukin-2 in immune-mediated dermatoses,providing a new idea for the clinical treatment of these diseases.

Guaiane-type sesquiterpenoids are most prevalent in the genus Cinnamomum. Hence this study investigates the structures, anti-nociceptive and IL-6 targeted anti-inflammatory potential of three novels C-14 guaiane-type sesquiterpenoids and two new monoterpenoids, isolated from Cinnamomum migao. The structures were precisely confirmed and characterized through the modern chromatographic and spectroscopic techniques of HRESIMS, 1 D NMR, 2 D NMR, experimental circular dichroism (ECD), and calculated (ECD). Novel sesquiterpenoids 1 and 2 exhibited significant anti-inflammatory activities against the NO production and pro-inflammatory cytokines. Their IC 50 values were determined as 9.52 and 13.42 μΜ against IL-6 mRNA, respectively. Similarly, subcutaneous injection of n-BuT and EA extracts showed a dose-dependent suppression of formalin-induced tonic biting/licking responses during the tonic antinociceptive phase. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of guaiane-type sesquiterpenoids 1 and 2 displayed that both compounds have a high level of GIT absorption, with a high zone of safety for cardiac and hepatotoxicity and no inhibition of cytochromes. In addition, molecular docking and simulation studies strengthen the anti-inflammatory potential of sesquiterpene 2 which showed a good binding affinity with IL-6 protein. Overall the inclusive results showed that the extracts and newly isolated guaiane-type sesquiterpenoids from C. migao will provide new evidence for the traditional use of this species to treat inflammation and nociception., Competing Interests: Declaration of Competing Interest Please declare any financial or personal interests that might be potentially viewed to influence the work presented. Interests could include consultancies, honoraria, patent ownership or other. If there are none state ‘there are none’., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: The surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron infections has affected most Chinese residents at the end of 2022, including a number of patients with systemic autoimmune rheumatic diseases (SARDs)., Methods: To investigate the antibody level of the Omicron variant in SARD patients after SARS-CoV-2 Omicron infection, we tested BA.5.2 and BF.7 Omicron variant IgG antibody levels using ELISA on blood samples collected from 102 SARD patients and 19 healthy controls (HCs). The type of SARD, demographics, concurrent treatment, doses of SARS-CoV-2 vaccines and outcomes were also recorded., Results: A total of 102 SARD patients (mean age: 40.3 years; 89.2% female), including 60 SLE, 32 RA and 10 other SARDs, were identified. Of these, 87 (85.3%) were infected with SARS-CoV-2. We found that the BA.5.2 and BF.7 antibody levels of infected SARD patients were lower than those of HCs ( P  <   0.05). Sixty-five (63.7%) patients had at least one dose of a SARS-CoV-2 vaccine. SARD patients with at least two doses of SARS-CoV-2 vaccine had a higher level of BA.5.2 and BF.7 antibodies than the unvaccinated group ( P  <   0.05). There was no evidence for a significant inhibitory effect of glucocorticoids (GCs) on the BA.5.2 and BF.7 Omicron variant antibody levels in SARD patients. SLE patients using biologic DMARDs had a lower BA.5.2 Omicron variant antibody level than patients using GCs and/or HCQ., Conclusion: These data suggest that patients with SARDs had a lower antibody response than HCs after Omicron infection., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: The femoral neck dynamic intersection system (FNS) is mechanically more stable than other internal fixation techniques. Current studies have confirmed that the structural design of FNS has good biomechanical properties in European and American populations. However, whether the suitability of the FNS's 130° main nail angle design for Asian populations has been thoroughly investigated remains unclear., Aim: To compare the biomechanical stability differences among different main nail angles of the FNS in the treatment of femoral neck fractures in Asian populations., Methods: Computed tomography data of the femur of healthy adult male volunteers were imported into Mimics software to create a three-dimensional model of the femur. The model was adapted to the curve using Geomagic software and imported into Solidworks software to construct the Pauwels I femoral neck fracture model and design the FNS internal fixation model using different main nail angles. Afterward, the models were assembled with the FNS fracture model and meshed using the preprocessing Hypermesh software. Subsequently, they were imported into Abaqus software to analyze and evaluate the biomechanical effects of different angles of the FNS main nail on the treatment of femoral neck fractures., Results: The peak displacement of the proximal femur under different angles of FNS fixation under stress was 7.446 millimeters in the 120° group and 7.416 millimeters in the 125° group; in the 130°, 135°, and 140° FNS fixation groups, the peak displacement was 7.324 millimeters, 8.138 millimeters, and 8.246 millimeters, respectively. In the 120° and 125° FNS fixation groups, the maximum stresses were concentrated at the main nail and the anti-rotation screw, which intersected the fracture line of the femur neck, resulting in peak stresses of 200.7 MPa and 138.8 MPa, respectively. Peak stresses of 208.8 MPa, 219.8 MPa, and 239.3 MPa were observed on the angular locking plate distal to the locking screw in the 130°, 135°, and 140° fixation groups., Conclusion: FNS has significant stress distribution properties, a minimal proximal femoral displacement, and an optimal stability for treating femoral neck fractures in Asian populations when performed with a 130° main nail angle., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease belonging to the localized form of pustular psoriasis. It is characterized by sterile pustule formation in palms and soles and a recurrent disease course. Although we have many treatments for PPP, there is no authoritative guidance., Areas Covered: A thorough search of PubMed was conducted to identify studies in PPP from 1973 onwards, with additional references to specific articles. Any treatment methods were outcomes of interest, including topical treatment, systemic treatment, biologics, other targeted treatments, phototherapy, and tonsillectomy., Expert Opinion: Topical corticosteroids are suggested as first-line therapy. Oral acitretin has become the most applied systemic retinoid recommended in PPP without joint involvement. For patients with arthritis, immunosuppressants like cyclosporin A and methotrexate are more recommended. UVA1, NB-UVB, and 308-nm excimer laser are effective phototherapy options. The combinations of topical or systemic agents and phototherapy may enhance the efficacy, particularly in recalcitrant cases. Secukinumab, ustekinumab, and apremilast are the most investigated targeted therapies. However, heterogeneous reported outcomes in clinical trials provided low-to-moderate quality evidence of their efficacy. Future studies are required to address these evidence gaps. We suggest managing PPP based on the acute phase, maintenance phase, and comorbidities.

Psoriasis is a chronic inflammatory skin disorder with a chronic relapsing course. Biologics have revolutionized the treatment of adult psoriasis with higher efficacy and favorable safety profile. Recently, more studies have focused on the use of biologics in pediatric psoriasis, and several biologics have been approved for use therein. This review is divided into two sections: the first part focuses on real-world studies on the use of biologics in pediatric psoriasis and the second part summarizes the findings of other clinical trials related to biologics in pediatric psoriasis. Case reports have been excluded from this review. Several biologics were used for treating pediatric psoriasis and the efficacy is encouraging. According to the studies included in this review, anti-IL-12/23 and anti-IL-17A for treating pediatric psoriasis might have a better efficacy than anti-TNF-α, but more data are needed., (© 2023 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Evolved over eons to encode biological assays, plants-derived natural products are still the first dawn of drugs. Most researchers have focused on natural compounds derived from commonly used Pimpinella species, such as P. anisum , P. thellungiana , P. saxifrage , and P. brachycarpa , to investigate their antioxidant, antibacterial, and anti-inflammatory properties. Ethnopharmacological studies demonstrated that the genus Pimpinella has the homology characteristics of medicine and food and mainly in the therapy of gastrointestinal dysfunction, respiratory diseases, deworming, and diuresis. The natural product investigation of Pimpinella spp . revealed numerous natural products containing phenylpropanoids, terpenoids, flavonoids, coumarins, sterols, and organic acids. These natural products have the potential to provide future drugs against crucial diseases, such as cancer, hypertension, microbial and insectile infections, and severe inflammations. It is an upcoming field of research to probe a novel and pharmaceutically clinical value on compounds from the genus Pimpinella . In this review, we attempt to summarize the present knowledge on the traditional applications, phytochemistry, and pharmacology of more than twenty-five species of the genus Pimpinella .

A phytochemical investigation on the roots of Aconitum austroyunnanense afforded three undescribed aconitine-type C 19 -diterpenoid alkaloids, austroyunnanines A-C (1-3). Structural elucidation of all the compounds were performed by spectral methods such as 1 D and 2 D ( 1 H- 1 H COSY, HMQC, and HMBC) NMR spectroscopy. The isolated alkaloids were tested in vivo for their antinociceptive properties. Consequently, austroyunnanine B (2) exhibited significant antinociceptive effect and its ID 50 value (48.0 μmol/kg) was 2-fold less than those of the positive control drugs aspirin and acetaminophen.

Background: Acute thoracic aortic dissection (ATAD) is a fatal condition characterized by tear of intima, formation of false lumen and rupture of aorta. However, the subpopulations of normal and dissected aorta remain less studied., Methods: Single-cell RNA sequencing was performed including 5 patients with ATAD and 4 healthy controls. Immunohistochemistry and immunofluorescence were used to verify the findings., Results: We got 8 cell types from human ascending aorta and identified 50 subpopulations including vascular smooth muscle cells (VSMCs), endothelial cells, fibroblasts, neutrophils, monocytes and macrophages. Six transmembrane epithelial antigen of prostate 4 metalloreductase (STEAP4) was identified as a new marker of synthetic VSMCs. CytoTRACE identified subpopulations with higher differentiation potential in specified cell types including synthetic VSMCs, enolase 1 + fibroblasts and myeloid-derived neutrophils. Synthetic VSMCs-derived C-X-C motif chemokine ligand 12 (CXCL12) might interact with neutrophils and fibroblasts via C-X-C motif chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3), respectively, which might recruit neutrophils and induce transdifferentitation of fibroblasts into synthetic VSMCs., Conclusion: We characterized signatures of different cell types in normal and dissected human ascending aorta and identified a new marker for isolation of synthetic VSMCs. Moreover, we proposed a potential mechanism that synthetic VSMCs might interact with neutrophils and fibroblasts via CXCL12-CXCR4/ACKR3 axis whereby deteriorating the progression of ATAD, which might provide new insights to better understand the development and progression of ATAD., (© 2022. The Author(s).)

Kaixinsan powder (KXS), a classic prescription of traditional Chinese Medicine (TCM), is widely used in the treatment of depression, but its mechanism remains unclear. The network pharmacology method was used to constructe the "herb-component-target" network, and elucidated KXS potential mechanisms of action in the treatment of depression. Moreover, molecular docking was applied to valid the important interactions between the ingredients and the target protein. The "herb-component-target" network indicated that the ingredients of Girinimbin, Gomisin B and Asarone, and the protein targets of ESR, AR and NR3C1 mostly contribute to the antidepressant effect of KXS. KEGG pathway analysis highlighted the most significant pathways associated with depression treatment, including neuroactive ligand-receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Go enrichment analysis indicated that the mechanism of KXS in treating depression was involved in the biological process of GPCR signal transduction, hormone metabolism and nerve cell apoptosis. Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed greater binding ability with key antidepressant target 5-HTR. In conclusion, this study preliminarily revealed key active components in KXS, including Gomisin B, Asarone, Ginsenoside Rg1, Polygalaxanthone III and Pachymic acid, could interact with multiple targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand -receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway)., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Triggering through abiotic stress, including chemical triggers like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metal Nickel on actinobacteria Streptomyces sp. SH-1327 to obtain a stress-derived compound was firstly investigated. A new compound cyclo-(D)-Pro-(D)-Phe (CDPDP) was triggered from the actinobacteria strain SH-1327 with the addition of nickel ions 1 mM. The stress compound was further evaluated for its anti-oxidant, analgesic, and anti-inflammatory activity against rheumatoid arthritis through in-vitro and in-vivo assays in albino mice. A remarkable in-vitro anti-oxidant potential of CDPDP was recorded with the IC 50 value of 30.06 ± 5.11 μg/ml in DPPH, IC 50 of 18.98 ± 2.91 against NO free radicals, the IC 50 value of 27.15 ± 3.12 against scavenging ability and IC 50 value of 28.40 ± 3.14 μg/ml for iron chelation capacity. Downregulation of pro-inflammatory mediators (NO and MDA), suppressed levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-Iβ) and upregulation of expressions of anti-oxidant enzymes (GSH, catalase, and GST) unveiled its anti-inflammatory potential. CDPDP was analyzed in human chondrocyte cell line CHON-001 and the results demonstrated that CDPDP significantly increased cell survival, and inhibited apoptosis of IL-1β treated chondrocytes and IL-1β induced matrix degrading markers. In addition, to evaluate the mitochondrial fitness of CHON-001 cells, CDPDP significantly upregulated pgc1-α, the master regulator of mitochondrial biogenesis, indicating that CDPDP provides protective effects in CHON-001 cells. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile of the CDPDP showed that CDPDP is safe in cases of hepatotoxicity, cardiotoxicity, and cytochrome inhibition. Furthermore, docking results showed good binding of CDPDP with IL-6-17.4 kcal/mol, and the simulation studies proved the stability between ligand and protein. Therefore, the findings of the current study prospect CDPDP as a potent anti-oxidant and a plausible anti-arthritic agent with a strong pharmacokinetic and pharmacological profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hassan, Abbas, Muhammad, Wu, Yan, Ali, Majid, Jin and Bungau.)

Objectives: Age-associated B cells (ABCs) are a recently identified B cell subset, whose expansion has been increasingly linked to the pathogenesis of autoimmune disorders. This study aimed to investigate whether ABCs are involved in the pathogenesis and underlying mechanisms of rheumatoid arthritis (RA)., Methods: ABCs were assessed in collagen-induced arthritis (CIA) mice and patients with RA using flow cytometry. Transcriptomic features of RA ABCs were explored using RNA-seq. Primary fibroblast-like synoviocytes (FLS) derived from the synovial tissue of patients with RA were cocultured with ABCs or ABCs-conditioned medium (ABCsCM). IL-6, MMP-1, MMP-3 and MMP-13 levels in the coculture supernatant were detected by ELISA. Signalling pathways related to ABCs-induced FLS activation were examined using western blotting., Results: Increased ABCs levels in the blood, spleen and inflammatory joints of CIA mice were observed. Notably, ABCs were elevated in the blood, synovial fluid and synovial tissue of patients with RA and positively correlated with disease activity. RNA-seq revealed upregulated chemotaxis-related genes in RA ABCs compared with those in naive and memory B cells. Coculture of FLS with RA ABCs or ABCsCM led to an active phenotype of FLS, with increased production of IL-6, MMP-1, MMP-3 and MMP-13. Mechanistically, ABCsCM-derived TNF-α promoted the upregulation of interferon-stimulated genes in FLS, with elevated phosphorylation of ERK1/2 and STAT1. Furthermore, blockage of ERK1/2 and Janus Kinase (JAK)-STAT1 pathways inhibited the activation of FLS induced by ABCsCM., Conclusions: Our results suggest that ABCs contribute to the pathogenesis of RA by inducing the activation of FLS via TNF-α-mediated ERK1/2 and JAK-STAT1 pathways., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Twelve flavonoids were isolated and purified from the ethyl acetate fraction of 95% ethanol extract of Dalbergia odorifera by heat reflux extraction, solvent extraction, recrystallization, normal phase silica gel, Sephadex LH-20, MCI gel and HPLC methods. The structures were identified with multiple spectroscopic methods, including 1 D-NMR, 2 D-NMR and MS. The compounds were identified as 6,7,8-trimethoxy-5,4'-dihydroxy isoflavone(1), medicarpin(2), 7,2'-dihydroxy-4'-methoxy-isoflavanol(3), biochanin A(4), prunetin(5), genistein(6), pratensein(7), 3-(4-hydroxyphenyl)-6-isopentenyl-7-methoxy-4H-chromen-4-one(8), tectorigenin(9), irisolidone(10), vestitol(11), and formononetin(12). Compound 1 was a new isoflavone, and compound 8 was isolated from D. odorifera for the first time. The results showed that compounds 1-3 had inhibitory effects on tyrosinase, with inhibition rates of 35.58%, 38.63% and 51.34% at the concentration of 1.0 mmol·L~(-1), respectively.

Thymic stromal lymphopoietin (TSLP), long known to be involved in Th2 response, is also implicated in multiple inflammatory dermatoses and cancers. The purpose of this study was to improve our understanding of the expression of TSLP in the skin of those dermatoses. Lesional specimens of representative immune-related dermatoses, including lichen planus (LP), discoid lupus erythematosus (DLE), eczema, bullous pemphigoid (BP), psoriasis vulgaris (PsV), sarcoidosis, and mycosis fungoides (MF), were retrospectively collected and analyzed by immunohistochemistry. Morphologically, TSLP was extensively expressed in the epidermis of each dermatosis, but the expression was weak in specimens of DLE. In a semiquantitative analysis, TSLP was significantly expressed in the epidermis in LP, BP, eczema, PsV, sarcoidosis, and MF. TSLP expression was higher in the stratum spinosum in LP, eczema, BP, PsV, and MF and higher in the stratum basale in sarcoidosis and PsV. Moreover, we found positive TSLP staining in the dermal infiltrating inflammatory cells of BP, PsV, and sarcoidosis. Our observation of TSLP in different inflammatory dermatoses might provide a novel understanding of TSLP in the mechanism of diseases with distinctly different immune response patterns and suggest a potential novel therapeutic target of those diseases., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2022 Si-Zhe Li et al.)

Background: The International System for Reporting Serous Fluid Cytopathology (TIS) was recently proposed. We retrospectively applied TIS recommendations for reporting the cytological diagnosis of serous effusions and reported our experience., Methods: All the serous effusions from January 2018 to September 2021 were retrieved from the database. Recategorization was performed using the TIS classification, the risk of malignancy (ROM) was calculated for each TIS category. In addition, on the basis of the original TIS classification, we further subdivided the TIS category IV (suspicious for malignancy, SFM) into 2 groups (IVa and IVb) according to cytological characteristics (quality and quantity) to explore the necessity of SFM subclassification. The performance evaluation was carried out using different samples (pleural, peritoneal and pericardial effusions) and preparation methods (conventional smears, liquid-based preparations and cell blocks)., Results: A total of 3633 cases were studied: 17 (0.5%) were diagnosed as 'nondiagnostic' (I, ND), 1100 (30.3%) as 'negative for malignancy' (II, NFM), 101 (2.8%) as 'atypia of undetermined significance' (III, AUS), 677 (18.6%) as 'suspicious for malignancy' (IV, SFM), and 1738 (47.8%) as 'malignant' (V, MAL). The ROMs for the categories were 38.5%, 28.6%, 52.1%, 99.4% and 100%, respectively. The ROM for SFM was significantly higher than that for AUS (P < 0.001), while the difference between the ROMs for IVa and IVb was insignificant. The sensitivity, negative predictive value (NPV) and diagnostic accuracy of liquid-based preparations were all superior to those of conventional smears and cell blocks in detecting abnormalities. Using the three preparation methods simultaneously had the highest sensitivity, NPV and diagnostic accuracy., Conclusion: Serous effusion cytology has a high specificity and positive predictive value (PPV), and TIS is a user-friendly reporting system. Liquid-based preparations could improve the sensitivity of diagnosis, and it is best to use three different preparation methods simultaneously for serous effusion cytologic examination., (© 2022. The Author(s).)

Three undescribed guaiane-type sesquiterpenes ( 1-3 ), and a monoterpenoid ( 4 ) along with eleven known compounds ( 5 - 15 ) were isolated from the crude extract of Litsea lancilimba Merr. The structures of all the isolated compounds were extensively elucidated on the basis of comprehensive spectroscopic techniques (HRESIMS, 1 D NMR, and 2 D NMR). Their relative and absolute configurations were comprehensively established by NOESY spectroscopy, circular dichroism (ECD) and the calculated ECD analysis. All the isolates were tested for anti-inflammatory activity by measuring the amount of nitric oxide production. Amongst tested compounds, compounds 1 - 3 exhibited moderate inhibitory activities against the production of nitric oxide with IC 50 value of 35.5, 32.1, 46.7  μ M in RAW264.7 cells stimulated by LPS, respectively.

In this study, we sequenced the complete mitogenome of Kentrochrysalis streckeri (Staudinger, 1880). The complete mitogenome sequence of K. streckeri is circular, 15,253 bp in size and contains 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a control region (CR). Nucleotide composition was A + T biased, and all the PCGs exhibited a positive AT-skew, which was reflected in the nucleotide composition, codon, and amino acid usage. Most PCGs start with ATG or ATT and stop with TAA. However, COX1 gene starts with CGA and three genes ( COX1 , COX2 , NAD5 ) use the incomplete stop codon T. Phylogenetic analyses showed that the relationship ( K. streckeri +(( Manduca sexta + Sphinx morio )+( Psilogramma increta +( Psilogramma menephron + Notonagemia analis scribae ))))., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Melanocytic nevi (MN) can be classified into three subtypes according to the depth of the nests of nevus cells which is important for management. High-frequency ultrasound (HF-US) can clearly reveal the lesion size, contour, depth, and internal structures. However, the HF-US studies of MN according to subtypes are limited. We aimed to describe the HF-US features of MN and explore its value in accurate classification., Materials and Methods: This retrospective study was conducted from January 2018 to November 2019. Eighty-five patients with MN were included and examined by 50 and 20 MHz HF-US. The HF-US features were recorded including morphological flatness, depth, shape, boundary, internal echogenicity, hyperechoic spots, lateral acoustic shadow, posterior echoic patterns, mushroom signs, and straw-hat signs. Each image was evaluated by two physicians independently, and the consistency was tested., Results: Eleven lesions could not be detected by HF-US. The rest 74 lesions underwent ultrasonic analysis. MN appeared as strip-shaped or oval, hypoechoic areas localized in the epidermis and dermis under ultrasonography. A strong consistency between HF-US and dermoscopy of determining the lesion depth was achieved (κ = 0.935, p < 0.001). The hyperechoic spots were found in 57.6% intradermal nevi. The mushroom signs were seen in 34.8% intradermal nevi, and the straw-hat signs were seen in all the compound nevi., Conclusion: MN can be correctly classified using HF-US, and it had a strong correlation with dermoscopic and clinical classification. HF-US could further reveal the internal morphological features of MN, which may support more precise classification and management., (© 2021 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

The aim of this review was to evaluate the efficacy and safety of tetracyclines for treatment of pemphigoid. We searched PubMed, EMBASE, Ovid, Web of Science, and the Cochrane Library for studies involving pemphigoid patients treated with tetracyclines published in English before 29 February 2020. References of included studies were also screened to widen the scope of the literature search. Data regarding predefined clinical outcomes of 341 patients from 77 studies were extracted and analyzed. A meta-analysis was conducted on the basis of 4 studies including 2 randomized controlled trials and 2 comparative studies. The patients had a mean age of 74.60 ± 13.18 years, 45.4% were males, and 54.6% were females. There were 185 patients with mild-to-moderate and 143 patients with severe disease. The average initial doses were 1.62 ± 0.39 g/day for tetracycline, 0.20 ± 0.01 g/day for doxycycline, and 0.11 ± 0.05 g/day for minocycline. The average time on tetracyclines was 3.74 ± 5.99 months, and 261 (81.3%) patients reported partial or complete remission. Relapses occurred in 72 (28.3%) cases. Adverse effects were experienced by 130 (41.9%) patients. The pooled ORs for short-term effectiveness, relapse, adverse effects, and 1-year survival in patients treated with oral tetracyclines vs. systemic corticosteroids were 0.40 (95% CI, 0.22-0.76), 0.69 (95% CI, 0.44-1.10), 0.47 (95% CI, 0.27-0.82) and 2.02 (95% CI, 1.16-3.50), respectively. Compared to doxycycline and minocycline, tetracycline was significantly associated with better treatment outcomes and fewer adverse effects (p < 0.05). This review revealed tetracyclines' efficacy and safety in pemphigoid treatment and may offer support for clinical use of tetracyclines in pemphigoid., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Low-density granulocytes (LDGs), a distinct subset of neutrophils that colocalize with peripheral blood mononuclear cells after density gradient centrifugation, have been observed in many immune-mediated diseases. LDGs are considered highly proinflammatory because of enhanced spontaneous formation of neutrophil extracellular traps, endothelial toxicity, and cytokine production. Concomitantly, increased numbers of LDGs are associated with the severity of many immune-mediated inflammatory diseases. Recent studies, with the help of advanced transcriptomic technologies, demonstrated that LDGs were a mixed cell population composed of immature subset and mature subset, and these two subsets showed different pathogenic features. In this review, we summarize the current knowledge on the composition, origin, and pathogenic properties of LDGs in several immune-mediated inflammatory diseases and discuss potential medical interventions targeting LDGs., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xin Ning et al.)

Compounds derived from plants have several anticancer properties. In the current study, one guaiane-type sesquiterpene dimer, vieloplain F, isolated from Xylopia vielana species, was tested against B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma. A comprehensive in silico analysis was conducted in this research to understand the pharmacological properties of a compound encompassing absorption, distribution, metabolism, excretion, and toxicity (ADMET), bioactivity score predictions, and molecular docking. During ADMET estimations, the FDA-approved medicine vemurafenib was hepatotoxic, cytochrome-inhibiting, and non-cardiotoxic compared to the vieloplain F. The bioactivity scores of vieloplain F were active for nuclear receptor ligand and enzyme inhibitor. During molecular docking experiments, the compound vieloplain F has displayed a higher binding potential with -11.8 kcal/mol energy than control vemurafenib -10.2 kcal/mol. It was shown that intermolecular interaction with the B-Raf complex and the enzyme's active gorge through hydrogen bonding and hydrophobic contacts was very accurate for the compound vieloplain F, which was then examined for MD simulations. In addition, simulations using MM-GBSA showed that vieloplain F had the greatest propensity to bind to active site residues. The vieloplain F has predominantly represented a more robust profile compared to control vemurafenib, and these results opened the road for vieloplain F for its utilization as a plausible anti-melanoma agent and anticancer drug in the next era.

Natural products of herbal origin are prodigious to display diverse pharmacological activities. In the present study, five guaiane-type sesquiterpene dimers, xylopidimers A   - E ( 1-5 ), isolated from Xylopia vielana species were tested against COX-2 protein target (PDB: 1CX2), a potent target for anti-inflammatory agents. To better understand the pharmacological properties of all these compounds, in this work, a systemic in silico study was performed on xylopidimers A-E using molecular docking, ADMET analysis and MD simulations. During ADMET predictions the two compounds xylopidimer C, D displayed best results as compared to others. The compound xylopidimer C was further evaluated for its MD simulations and its molecular interactions with COX2 complex showed clear interactions with active gorge of the enzyme through hydrogen bonding as well as hydrophobic contacts. The xylopidimer C has shown the best binding potential with -10.57Kcal/mol energy with 17.92 nano molar of predicted inhibition constant better than Ibuprofen and Felbinac. These findings provide enough significant information for designing and developing novel targeted base anti-inflammatory drugs from guaiane dimers.

Background: Natural products from herbs are abundant and display powerful anti-cancer activities., Objectives: In the current study, B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma, was tested against two guaiane-type sesquiterpene dimers, xylopin E-F, obtained from Xylopia vielana., Methods: In this work, a systematic in silico study using ADMET analysis, bioactivity score forecasts, and molecular docking along with its simulations was conducted to understand compounds' pharmacological properties., Results: During ADMET predictions of both the compounds, xylopin E-F displayed a safer profile in hepatotoxicity and cytochrome inhibition, and only xylopin F was shown to be non-cardiotoxic compared to the FDA-approved drug vemurafenib. Both the compounds were proceeded to molecular docking experiments using Autodock docking software, and both the compounds, xylopin E-F, displayed higher binding potential with -11.5Kcal/mol energy compared to control vemurafenib (-10.2 Kcal/mol). All the compounds were further evaluated for their MD simulations, and their molecular interactions with the B-Raf kinase complex displayed precise interactions with the active gorge of the enzyme by hydrogen bonding., Conclusion: Overall, xylopin F had a better profile relative to xylopin E and vemurafenib, and these findings indicated that this bio-molecule could be used as an anti-melanoma agent and as a possible anti-cancer drug in the future. Therefore, this is a systematically optimized in silico approach for creating an anti-cancer pathway for guaiane dimers against the backdrop of its potential for future drug development., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Elicitation through abiotic stress, including chemical elicitors like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metals on actinobacteria Streptomyces sp. SH-1312 for secondary metabolite production, with strong pharmacological activity, along with pharmacokinetics profile, was firstly investigated. The optimum metal stress conditions consisted of actinobacteria strain Streptomyces sp. SH-1312 with addition of mix metals (Co 2+ + Zn 2+ ) ions at 0.5 mM in Gause's medium. Under these conditions, the stress metabolite anhydromevalonolactone (MVL) was produced, which was absent in the normal culture of strain and other metals combinations. Furthermore, the stress metabolite was also evaluated for its anti-oxidant and cytotoxic activities. The compound exhibited remarkable anti-oxidant activities, recording the IC 50 value of 19.65 ± 5.7 µg/mL in DPPH, IC 50 of 15.49 ± 4.8 against NO free radicals, the IC 50 value of 19.65 ± 5.22 µg/mL against scavenging ability, and IC 50 value of 19.38 ± 7.11 µg/mL for iron chelation capacity and the cytotoxic activities against PC3 cell lines were recorded with IC 50 values of 35.81 ± 4.2 µg/mL after 24 h, 23.29 ± 3.8 µg/mL at 48 h, and 16.25 ± 6.5 µg/mL after 72 h. Further mechanistic studies have revealed that the compound MVL has shown its pharmacological efficacy by upregulation of P53 and BAX while downregulation of BCL-2 expression, indicating that MVL is following apoptosis in varying degrees. To better understand the pharmacological properties of MVL, in this work, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) were also evaluated. During ADMET predictions, MVL has displayed a safer profile in case of hepatotoxicity, cytochrome inhibition and also displayed as non-cardiotoxic. The compound MVL showed good binding energy in the molecular docking studies, and the results revealed that MVL bind in the active region of the target protein of P53 and BAX. This work triumphantly announced a prodigious effect of heavy metals on actinobacteria with fringe benefits as a key tool of MVL production with a strong pharmacological and pharmacokinetic profile.

Eosinophils are a minor component of circulating granulocytes, which are classically viewed as end-stage effector cells in host defense against helminth infection and promoting allergic responses. However, a growing body of evidence has emerged showing that eosinophils are versatile leukocytes acting as an orchestrator in the resolution of inflammation. Rheumatoid arthritis (RA) is the most common chronic inflammatory disease characterized by persistent synovitis that hardly resolves spontaneously. Noteworthy, a specific population of eosinophils, that is, regulatory eosinophils (rEos), was identified in the synovium of RA patients, especially in disease remission. Mechanistically, the rEos in the synovium display a unique pro-resolving signature that is distinct from their counterpart in the lung. Herein, we summarize the latest understanding of eosinophils and their emerging role in promoting the resolution of arthritis. This knowledge is crucial to the design of new approaches to rebalancing immune homeostasis in RA, considering that current therapies are centered on inhibiting pro-inflammatory cytokines and mediators rather than fostering the resolution of inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qin, Jin, Li and Chen.)

Psoriasis is a chronic inflammatory disease that involves both the innate and adaptive immune systems. Type I interferons (IFNs), the production of which is partially regulated by toll-like receptors (TLRs), play an important role in the pathogenesis of psoriasis, especially psoriasis caused by skin trauma, known as the Koebner phenomenon. IFN regulatory factors (IRFs) function in both innate and adaptive immune responses, and their effect is associated with the regulation of type I IFNs. In this review, we focus on recent advances in understanding the expression of TLRs, IRFs, and type I IFNs in psoriasis. We also highlight the interplay among TLRs, IRFs, and type I IFNs., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To study the specific alignment and structure of cancellous bone within the talus in order to understand the mechanism of force transmission within the bone and to provide some theoretical basis for the repositioning of talar fractures and the design of prostheses. Methods: In January 2020, a total of 40 adult talar bone specimens were scanned by Micro-CT in 20 pairs obtained from the Department of Orthopedics of Tianjin Hospital. The bone volume fraction, bone surface area fraction, trabecular thickness, number of trabeculae, trabecular pattern factor of the head, neck and body of the talus were calculated, and the differences in each parameter were compared between different parts of the same side and different sides of the same part, respectively. The talus was cut into 2 mm thick slices in the coronal, sagittal and horizontal planes using a hard tissue slicer, and the slices were then scanned using high-resolution X-rays to describe the bone structure. Results: There were no statistically significant differences between the medial and lateral talar and right and left side in lateral trabecular bone volume fraction, bone surface area fraction, trabecular thickness, trabecular number, trabecular pattern factors (all P >0.05). The number of trabeculae in the talar head, neck and body was 1.608±0.150, 1.639±0.142 and 1.749±0.159, respectively; trabecular thickness (μm) in the talar head, neck and body was 0.378±0.054, 0.370±0.053 and 0.331±0.062, respectively; and the trabecular pattern factors (mm -1 ) in the talar head, neck and body was -0.407±0.699, -0.478±0.848 and -1.029±0.851, respectively. There were significant differences between talar head, neck and the talar body trabeculae in terms of the number of trabeculae, trabecular thickness,trabecular pattern factor parameters(all P <0.05). The structure of the talar body trabeculae was found to consist of plate trabeculae arranged vertically parallel to each other in the coronal, sagittal and horizontal planes. The talar neck trabeculae were twisted, external-superior to internal-inferior reticular plate structure that travelled posteriorly and anteriorly, and the talar head trabeculae consisted of similarly parallel aligned semi-arc-shaped external-superior and internal-inferior trabeculae. Conclusion: The talar trabeculae are clearly directional and functional, so anatomical reduction should be achieved after the fracture; at the same time, the design of the talar prosthesis should take into account the stress distribution and direction of the prosthesis during walking and standing.

The phytochemical assessment of Cinnamomum migao H. W. Li fruits illustrated the isolation and identification of ten undescribed guaiane-type sesquiterpenoids "miganoids A-J″ and one undescribed sesquiterpene "7(S)-(hydroxypropanyl)-3-methyl-2-(4-oxopentyl) cyclohex-2-en-1-one". The extensive analysis of HRESIMS, 1D NMR, 2D NMR, experimental circular dichroism (ECD), and calculated (ECD) analysis entirely corroborated the configuration and confirmation of these isolated compounds. Moreover, the anti-inflammatory properties of the reported compounds were established by determining the LPS induced nitric oxide production. In the current study, miganoid C is testified the most active compound with about 89% NO inhibition. Additionally, miganoids C, E, and G also exhibited moderate inhibitory effects against the pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). The IC 50 values for miganoid C and miganoid G were determined as 19.4 and 14.5 μΜ against TNF-α mRNA, respectively., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Psoriasis is a chronic immune-mediated skin disorder. Systemic inflammation plays an important role in the pathogenesis of psoriasis., Methods: A total of 477 patients with psoriasis vulgaris (PsV, n = 347), generalized pustular psoriasis (GPP, n = 37), erythrodermic psoriasis (PsE, n = 45), arthritic psoriasis (PsA, n = 25) and mixed psoriasis (n = 23), and 954 healthy control subjects were included in the study. Demographic, clinical, and laboratory information were collected and compared between subgroups., Results: Compared with the healthy control group, patients with psoriasis had higher total white blood cell (WBC), neutrophil, platelet counts, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR), but lower hemoglobin (Hb) levels, lymphocyte and red blood cell (RBC) counts. NLR values in the PsV group were significantly lower than those in the GPP, PsE, and PsA groups, with GPP group being the highest. PLR values in the PsV group were significantly lower than those in the GPP, PsE, and PsA groups. There was no significant correlation between the psoriasis area severity index (PASI) score and either the NLR or PLR in the PsV group., Conclusions: Elevated NLR and PLR were associated with psoriasis and differed between subtypes, suggesting that they could be used as markers of systemic inflammation in psoriasis patients., (© 2021. The Author(s).)

Background: To investigate the efficacy and safety of Dermalax in the correction of moderate to severe nasolabial folds (NLFs) compared to Restylane., Methods: A total of 324 subjects with moderate to severe NLFs were enrolled in this multicenter, randomized, double-blind, active-controlled clinical study. Eligible subjects were randomly assigned to the test group received Dermalax injection ( n  = 162) or control group received Restylane injection ( n  = 162). Clinical efficacy and safety were assessed based on the Wrinkle Severity Rating Scale (WSRS) and the Global Esthetic Improvement Scale(GAIS) at weeks 2, 8, 16, 24, 36 and 48 weeks after injection., Results: At week 24, similar improvements of effective rate were obtained on the Dermalax group (93.75%) and Restylane group (89.44%). Significances were found at 36 weeks and 48 weeks after injection, Dermalax seemed be better than Restylane in maintaining the effect in the later period. The improvement of mean WSRS score for test group was superior to that of control group with significance. GAIS scores rated at week 24 were 1.65 VS 1.94 ( p  < .001) and 2.10 VS 2.27 ( p  = .060), seperately., Conclusions: Dermalax was no inferior to or better than that of the control filler Restylane in correcting of moderate to severe NLFs in Chinese subjects.