Lichen planus pemphigoides induced by anti-PD-1 antibody: A case only involved in oral mucosa with excellent topical treatment efficiency.

Lichen planus pemphigoides (LPP) is a rare autoimmune subepidermal disease that can occur in patients receiving immune checkpoint inhibitors. Its clinical manifestations are combined with the characteristics of lichen planus with bullous pemphigoid that can occur on either skin or oral mucosa. It should be noted that oral LPP is very rare. Here, we report a novel case of oral LPP induced by an anti-PD-1 agent. The patient presented with typical clinical features in oral mucosa, and the diagnosis was based on histopathology and immunological studies. Given that the patient was receiving an anti-PD-1 agent, topical therapy was chosen, and a nice therapeutic effect was obtained. No significant recurrence was observed after a 2-year follow-up. A good and stable therapeutic effect achieved by rapid and local symptomatic medication suggests that accurate and sensitive diagnosis is necessary.

The Medial Canthus Fibrous Band's Impact on Epicanthal Fold Severity and Classification in Asians: Implications for Epicanthoplasty.

BACKGROUND: The epicanthal fold (EF) is a semilunar skin fold located in the medial canthus in most Asians. The medial canthus fibrous band (MCFB) reportedly plays a critical role in EF formation. Variations in MCFB shape and size affect the severity and type of EF. OBJECTIVES: We aimed to analyze MCFB variations in different types and severities of EF and explore the effect of the MCFB resection epicanthoplasty technique (MCFB epicanthoplasty). METHODS: Surgical videos of 40 patients undergoing MCFB epicanthoplasty in our department were reviewed. The MCFB (area), transverse dimension, vertical dimension, upper eyelid direction length (UEDL), and lower eyelid direction length (LEDL) were measured. For aesthetic assessment, 37 patients were followed up for 6 months; intercanthal distance (ICD) and horizontal lid fissure length (HLFL) were measured. Preoperative and postoperative ICD/HLFL ratios were compared. Postoperative scar recovery was evaluated with the Patient and Observer Scar Assessment Scale. Statistical significance was set at P < .05. RESULTS: The MCFB diameter and area were larger for severe EF than for moderate EF (P < .01). Patients with severe EF had larger LEDL than UEDL (P < .01). The tarsalis type had a larger LEDL than the palpebralis type with the same severity (P < .01). MCFB epicanthoplasty yielded favorable postoperative cosmetic effects and scar recovery. Postoperative ICD decreased, while HLFL increased compared to preoperative values (P < .001). The ICD/HLFL ratio was significantly lower postoperatively than preoperatively (P < .001). Postoperative ICD/HLFL ratio was 1.2:1. CONCLUSIONS: The MCFB affects the severity and type of EF. MCFB epicanthoplasty effectively corrected moderate to severe EF.

Significant efficacy of short-course, low-concentration betamethasone mouthwash therapy for severe erosive oral lichen planus: a randomized controlled trial.

OBJECTIVES: To evaluate the short-term efficacy of low-concentration betamethasone mouthwash for severe erosive oral lichen planus (EOLP). MATERIALS AND METHOD: In this randomized, investigator-blind, positive-controlled trial, OLP patients with erosive lesions received betamethasone mouthwash (0.137 mg/mL) or dexamethasone mouthwash (0.181 mg/mL) three times daily for 2 or 4 weeks and were followed up for 3 months to observe recurrence. The primary outcome was the week-2 reduction in erosive area. RESULTS: Fifty-seven participants were randomized to betamethasone (n = 29) and dexamethasone (n = 28). At week 2, participants using betamethasone (n = 28) experienced a greater reduction in erosive area than gargling with dexamethasone (n = 26). Similarly, secondary outcomes, including the healing proportion of erosions, reduced pain level, reduction in atrophic area, Thongprasom score, and recurrence interval, showed the superiority of betamethasone. At week 4, betamethasone (n = 7) was not superior to dexamethasone (n = 15) in further reducing lesional area and pain level. No serious adverse events were documented. CONCLUSIONS: The 0.137 mg/mL compound betamethasone mouthwash exhibited significant efficacy in rapidly enhancing erosion healing within 2 weeks and extending the recurrence interval with a good safety profile. CLINICAL RELEVANCE: This study proved the significant efficacy of short-course 0.137 mg/mL betamethasone mouthwash therapy for treating erosion and pain, providing a novel topical agent for patients with severe EOLP. TRIAL REGISTRATION: This study was prospectively registered at the International Clinical Trials Registry Platform ( ChiCTR1800016507 ) on 5 June 2018.

Identification and Biological Validation of a Chemokine/Chemokine Receptor-Based Risk Model for Predicting Immunotherapeutic Response and Prognosis in Head and Neck Squamous Cell Carcinoma.

Over 80% of head and neck squamous cell carcinoma (HNSCC) patients failed to respond to immunotherapy, which can likely be attributed to the tumor microenvironment (TME) remolding mediated by chemokines/chemokine receptors (C/CR). This study aimed to establish a C/CR-based risk model for better immunotherapeutic responses and prognosis. After assessing the characteristic patterns of the C/CR cluster from the TCGA-HNSCC cohort, a six-gene C/CR-based risk model was developed to stratify patients by LASSO Cox analysis. The screened genes were multidimensionally validated by RT-qPCR, scRNA-seq, and protein data. A total of 30.4% of patients in the low-risk group had better responses to anti-PD-L1 immunotherapy. A Kaplan-Meier analysis showed that patients in the low-risk group had longer overall survival. A time-dependent receiver operating characteristic curve and Cox analyses indicated that risk score served as an independent predictive indicator. The robustness of the immunotherapy response and prognosis prediction was also validated in independent external datasets. Additionally, the TME landscape revealed that the low-risk group was immune activated. Furthermore, the cell communication analysis on the scRNA-seq dataset revealed that cancer-associated fibroblasts were the main communicators within the C/CR ligand-receptor network of TME. Collectively, The C/CR-based risk model simultaneously predicted immunotherapeutic response and prognosis, potentially optimizing personalized therapeutic strategies of HNSCC.

Biofilm-Based Biocatalysis for Galactooligosaccharides Production by the Surface Display of ß-Galactosidase in Pichia pastoris.

Galactooligosaccharides (GOS) are one of the most important functional oligosaccharide prebiotics. The surface display of enzymes was considered one of the most excellent strategies to obtain these products. However, a rough industrial environment would affect the biocatalytic process. The catalytic process could be efficiently improved using biofilm-based fermentation with high resistance and activity. Therefore, the combination of the surface display of ß-galactosidase and biofilm formation in Pichia pastoris was constructed. The results showed that the catalytic conversion rate of GOS was up to 50.3% with the maximum enzyme activity of 5125 U/g by screening the anchorin, and the number of the continuous catalysis batches was up to 23 times. Thus, surface display based on biofilm-immobilized fermentation integrated catalysis and growth was a co-culture system, such that a dynamic equilibrium in the consolidated integrative process was achieved. This study provides the basis for developing biofilm-based surface display methods in P. pastoris during biochemical production processes.

The diminishing effects of winter heating on air quality in northern China.

Cleaner winter heating has been promoted to abate the winter air pollution in northern China. Although improvements in air quality have been observed, the effectiveness and mechanism of cleaner heating measures on air quality have not been examined on the empirical ground. In this study, we estimate the annual effects of winter heating policy on air quality from 2014 to 2017 using a regression discontinuity design (RDD) and dynamic regression model. The results show that winter heating aggravates Air Quality Index (AQI). Specifically, the AQI raised by winter heating reduce from 85.3 in 2014 to 24.1 in 2017, indicating diminishing effects of winter heating with the implementation of clean heating measures. The heterogeneous characteristics of winter heating in terms of different pollutants and city scales are further quantified. The effects of clean heating are more evident for particulate pollutants (PM2.5 and PM10) than for SO2, NO2, CO and O3. The promotion of clean heating is more effective in larger cities. These findings provided insights into the diminishing air pollution change with continuous advancement in clean heating policy and the heterogeneity among cities and pollutants should be taken into account when formulating future policies in response to energy transition and climate change.

A Wireless Real-Time Continuous Monitoring System for the Internal Movements of Mountain Glaciers Using Sensor Networks.

With the escalation of global warming, the shrinkage of mountain glaciers has accelerated globally, the water volume from glaciers has changed, and relative disasters have increased in intensity and frequency (for example, ice avalanches, surging glaciers, and glacial lake outburst floods). However, the wireless monitoring of glacial movements cannot currently achieve omnidirectional, high-precision, real-time results, since there are some technical bottlenecks. Based on wireless networks and sensor application technologies, this study designed a wireless monitoring system for measuring the internal parameters of mountain glaciers, such as temperature, pressure, humidity, and power voltage, and for wirelessly transmitting real-time measurement data. The system consists of two parts, with a glacier internal monitoring unit as one part and a glacier surface base station as the second part. The former wirelessly transmits the monitoring data to the latter, and the latter processes the received data and then uploads the data to a cloud data platform via 4G or satellite signals. The wireless system can avoid cable constraints and transmission failures due to breaking cables. The system can provide more accurate field-monitoring data for simulating glacier movements and further offers an early warning system for glacial disasters.

Microenvironment in Oral Potentially Malignant Disorders: Multi-Dimensional Characteristics and Mechanisms of Carcinogenesis.

Oral potentially malignant disorders (OPMDs) are a group of diseases involving the oral mucosa and that have a risk of carcinogenesis. The microenvironment is closely related to carcinogenesis and cancer progression by regulating the immune response, cell metabolic activities, and mechanical characteristics. Meanwhile, there are extensive interactions between the microenvironments that remodel and provide favorable conditions for cancer initiation. However, the changes, exact roles, and interactions of microenvironments during the carcinogenesis of OPMDs have not been fully elucidated. Here, we present an updated landscape of the microenvironments in OPMDs, emphasizing the changes in the immune microenvironment, metabolic microenvironment, mechanical microenvironment, and neural microenvironment during carcinogenesis and their carcinogenic mechanisms. We then propose an immuno-metabolic-mechanical-neural interaction network to describe their close relationships. Lastly, we summarize the therapeutic strategies for targeting microenvironments, and provide an outlook on future research directions and clinical applications. This review depicts a vivid microenvironment landscape and sheds light on new strategies to prevent the carcinogenesis of OPMDs.

A case of Melkersson-Rosenthal syndrome with endocrine disorders: Extraordinary efficiency of hydroxychloroquine and mechanism hypothesis.

BACKGROUND AND PURPOSE: Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disease. In addition to the traditional clinical triad, there is also a diversity of clinical signs, and it may be related to other systemic diseases. METHODS: In the present study, we report a case of MRS with endocrine disorders that exhibits extraordinary therapeutic efficiency by using hydroxychloroquine (HCQ), explore whether there is an internal connection between MRS and endocrine disorders, and discuss the mechanism of the therapeutic efficiency of using HCQ. The hypothesis proposed for the first time is that MRS may essentially be a systemic granulomatous disease. RESULTS: The physical examination revealed orofacial swelling and fissured tongue. The histopathologic examination showed epithelioid granulomas. Combined with the other examination, this case was diagnosed as incomplete MRS. HCQ and local drugs were introduced. The patient achieved clinical recovery and psychological cure by the 18-week follow-up, and the 1-year follow-up found no reactivation of MRS. Moreover, the levels of cortisol and adrenocorticotropic were within normal ranges. CONCLUSIONS: After the drug therapy was targeted at granuloma, not only did all of the symptoms related to MRS disappear, but the endocrine system also returned to normal. It is speculated that the endocrine disorder in this patient may be related to MRS. We further propose the first-time hypothesis that MRS may essentially be a systemic granulomatous disease. It provides a new medication method with high-level efficiency.

The hypothesis of tumor-associated macrophages mediating semi-phagocytosis of cancer cells in distant metastasis.

Tweetable abstract Tumor-associated macrophages might promote the distant metastasis of tumor cells by semi-phagocytosis. The authors propose that this newly discovered process occurs in tumor-associated macrophages and may lead to a novel approach for blocking cancer metastasis.

Coping Styles for Mediating the Effect of Resilience on Depression Among Medical Students in Web-Based Classes During the COVID-19 Pandemic: Cross-sectional Questionnaire Study.

BACKGROUND: Due to strict, nationwide, comprehensive COVID-19 protective measures, including home quarantine, all Chinese medical students began taking web-based classes beginning in the spring semester of 2020. Home quarantine, web-based classes, and the stress surrounding the COVID-19 pandemic may have triggered an increased incidence of mental health problems among medical students. Although there have been increasing amounts of literature on depression among medical students, studies focusing on positive psychological resources, such as resilience during the COVID-19 pandemic, still need to be expanded. OBJECTIVE: This study aims to assess depression among medical students who are taking web-based classes during the COVID-19 pandemic and to investigate the role of coping styles as mediators between resilience and depression. METHODS: A cross-sectional study of 666 medical students involving stratified sampling in Shenyang, Liaoning Province, China, was completed between March 20 and April 10, 2020. The participants responded to a self-administered, smartphone-based questionnaire, which included the Patient Health Questionnaire-9, Simplified Coping Style Questionnaire, and Ego Resilience 89 Scale. Hierarchical linear regression and structural equation modeling were used in this study. RESULTS: The prevalence of depression among the participants was 9.6% (64/666) in this study. The regression analysis revealed that grade (the year in which the medical student was in training) (P=.013), how well students adapted to web-based classes (P<.001), their levels of resilience (P=.04), and their coping styles were independent predictors for depression (P<.001). Resilience and positive coping styles were negatively related to depression (resilience: P=.04; positive coping styles: P<.001), and negative coping styles were positively related to depression (P<.001). The structural equation modeling analysis showed that the effect of resilience on depression was partially mediated by coping styles (P=.007). CONCLUSIONS: In this study, it was found that the prevalence of depression was slightly low and coping styles mediated the association between resilience and depression among medical students during the COVID-19 pandemic. These findings have significant implications for future studies. Future studies and interventions should aim to improve resilience and promote positive coping styles.

Heterogeneous effects of COVID-19 lockdown measures on air quality in Northern China.

In response to the spread of COVID-19, China implemented a series of control measures. The causal effect of these control measures on air quality is an important consideration for extreme air pollution control in China. Here, we established a difference-in-differences model to quantitatively estimate the lockdown effect on air quality in the Beijing-Tianjin-Hebei (BTH) region. We found that the lockdown measures did have an obvious effect on air quality. The air quality index (AQI) was reduced by 15.2%, the concentration of NO2, PM10, PM2.5, and CO were reduced by 37.8%, 33.6%, 21.5%, and 20.4% respectively. At the same time, we further explored the heterogeneous effects of travel restrictions and the control measure intensity on air quality. We found that the traffic restrictions, especially the restriction of intra-city travel intensity (TI), exhibited a significant heterogeneous effect on NO2 with a decrease of approximately 13.6%, and every one-unit increase in control measures intensity reduced the concentration of air pollutants by approximately 2-4%. This study not only provides a natural, experimental basis for control measures on air quality but also indicates an important direction for future control strategies. Importantly, determining the estimated effect helps formulate accurate and effective intervention measures on the differentiated level of air pollution, especially on extreme air pollution.

Protocol for Stereoselective Construction of Highly Functionalized Dienyl Sulfonyl Fluoride Warheads.

A pyrrolidine-mediated Knoevenagel-type reaction for highly stereoselective construction of novel α-halo-1,3-dienylsulfonyl fluorides was achieved in up to 100% Z-selectivity and high yields at room temperature from condensation of the readily available aldehydes and halomethanesulfonyl fluorides. This protocol provided a class of unique α-halo-1,3-dienylsulfonyl fluorides with wide scope and excellent functional group compatibility. The α-halo-1,3-dienylsulfonyl fluorides were used as versatile building blocks in sulfur fluoride exchange click chemistry, Suzuki reaction, and Sonogashira reaction for the assembly of highly functionalized dienyl sulfonyl fluoride derivatives to be applied as covalent warheads for the discovery of new drugs.

Light-induced [2 + 2] cycloadditions for the construction of cyclobutane-fused pyridinyl sulfonyl fluorides.

Cyclobutanes are an important class of motifs present in a wide range of natural products and other biologically significant molecules. A photocatalytic [2 + 2] cycloaddition between pyridones or isoquinolones and ethenesulfonyl fluoride was achieved, providing a portal to a class of unique cyclobutane-fused pyridinyl sulfonyl fluorides with quaternary rigid rings (30 examples). Further applications of these novel sulfonyl fluoride molecules in SuFEx click chemistry were also accomplished, providing the corresponding sulfonates and sulphonamides with reasonable yields.

Design, synthesis and biological evaluation of novel arylpropionic esters for the treatment of acute kidney injury.

Acute kidney injury (AKI) is associated with a strong inflammatory response, and inhibiting the response effectively prevents or ameliorates AKI. A series of novel arylpropionic esters were designed, synthesized and evaluated their biological activity in LPS-stimulated RAW264.7 cells. Novel arylpropionic esters bearing multi-functional groups showed significant anti-inflammatory activity, in which, compound 13b exhibited the most potent activity through dose-dependent inhibiting the production of nitric oxide (NO, IC50 = 3.52 µM), TNF-α and IL-6 (84.1% and 33.6%, respectively), as well as suppressing the expression of iNOS, COX-2 and TLR4 proteins. In C57BL/6 mice with cisplatin-induced AKI, compound 13b improved kidney function, inhibited inflammatory development, and reduced pathological damage of kidney tissues. In brief, this arylpropionic ester scaffold may be developed as anti-inflammatory agents.

Clickable coupling of carboxylic acids and amines at room temperature mediated by SO2F2: a significant breakthrough for the construction of amides and peptide linkages.

The construction of amide bonds and peptide linkages is one of the most fundamental transformations in all life processes and organic synthesis. The synthesis of structurally ubiquitous amide motifs is essential in the assembly of numerous important molecules such as peptides, proteins, alkaloids, pharmaceutical agents, polymers, ligands and agrochemicals. A method of SO2F2-mediated direct clickable coupling of carboxylic acids with amines was developed for the synthesis of a broad scope of amides in a simple, mild, highly efficient, robust and practical manner (>110 examples, >90% yields in most cases). The direct click reactions of acids and amines on a gram scale are also demonstrated using an extremely easy work-up and purification process of washing with 1 M aqueous HCl to provide the desired amides in greater than 99% purity and excellent yields.

Installation of -SO2F groups onto primary amides.

A protocol of SO2F2-mediated installation of sulfonyl fluoride onto primary amides has been developed providing a new portal to sulfur(VI) fluoride exchange (SuFEx) click chemistry. The generated molecules contain pharmaceutically important amide and -SO2F moieties for application in the discovery of new therapeutics.

Chemoselective synthesis of diaryl disulfides via a visible light-mediated coupling of arenediazonium tetrafluoroborates and CS2.

A highly efficient and chemoselective method for the synthesis of diaryl disulfides is developed via a visible light-promoted coupling of readily accessible arenediazonium tetrafluoroborates and CS2. This practical and convenient protocol provides a direct pathway for the assembly of a series of disulfides in an environmentally friendly manner with good to excellent yields.