SERPINB3/B4 is Increased in Psoriasis and Rosacea Lesions and has Pro-inflammatory Effects in Mouse Models of these Diseases.

Psoriasis and rosacea are both chronic inflammatory skin disorders resulted from aberrant keratinocyte-immune cell crosstalk, but the common molecular foundations for these two conditions are poorly understood. Here, we reveal that both psoriasis and rosacea patients, as well as their mice models, have significantly elevated expressions of SERPINB3/B4 (members of serine protease inhibitor) in the lesional skin. Skin inflammation in mice that resembles both psoriasis and rosacea is prevented by SERPINB3/B4 deficiency. Mechanistically, we demonstrate that SERPINB3/B4 positively induces NF-κB signaling activation, thereby stimulating disease-characteristic inflammatory chemokines and cytokines production in keratinocytes, and promoting the chemotaxis of CD4+ T cells. Our results suggest that, in keratinocytes, SERPINB3/B4 may be involved in the pathogenesis of both psoriasis and rosacea by stimulating NF-κB signaling, and they indicate a possible treatment overlap between these two diseases.

Robust Thiazole-Linked Covalent Organic Frameworks for Water Sensing with High Selectivity and Sensitivity.

The rational design of covalent organic frameworks (COFs) with hydrochromic properties is of significant value because of the facile and rapid detection of water in diverse fields. In this report, we present a thiazole-linked COF (TZ-COF-6) sensor with a large surface area, ultrahigh stability, and excellent crystallinity. The sensor was synthesized through a simple three-component reaction involving amine, aldehyde, and sulfur. The thiazole and methoxy groups confer strong basicity to TZ-COF-6 at the nitrogen sites, making them easily protonated reversibly by water. Therefore, TZ-COF-6 displayed color change visible to the naked eye from yellow to red when protonated, along with a red shift in absorption in the ultraviolet-visible diffuse reflectance spectra (UV-vis DRS) when exposed to water. Importantly, the water-sensing process was not affected by polar organic solvents, demonstrating greater selectivity and sensitivity compared to other COF sensors. Therefore, TZ-COF-6 was used to detect trace amounts of water in organic solvents. In strong polar solvents, such as N,N-dimethyl formamide (DMF) and ethanol (EtOH), the limit of detection (LOD) for water was as low as 0.06% and 0.53%, respectively. Even after 8 months of storage and 15 cycles, TZ-COF-6 retained its original crystallinity and detection efficiency, displaying high stability and excellent cycle performance.

Correction: A Novel Convolutional Neural Network for the Diagnosis and Classification of Rosacea: Usability Study.

[This corrects the article DOI: 10.2196/23415.].

Integrated analysis of gut metabolome, microbiome, and brain function reveal the role of gut-brain axis in longevity.

The role of microbiota-gut-brain axis in modulating longevity remains undetermined. Here, we performed a multiomics analysis of gut metagenomics, gut metabolomics, and brain functional near-infrared spectroscopy (fNIRS) in a cohort of 164 participants, including 83 nonagenarians (NAs) and 81 non-nonagenarians (NNAs) matched with their spouses and offspring. We found that 438 metabolites were significantly different between the two groups; among them, neuroactive compounds and anti-inflammatory substances were enriched in NAs. In addition, increased levels of neuroactive metabolites in NAs were significantly associated with NA-enriched species that had three corresponding biosynthetic potentials: Enterocloster asparagiformis, Hungatella hathewayi and Oxalobacter formigenes. Further analysis showed that the altered gut microbes and metabolites were linked to the enhanced brain connectivity in NAs, including the left dorsolateral prefrontal cortex (DLPFC)-left premotor cortex (PMC), left DLPFC-right primary motor area (M1), and right inferior frontal gyrus (IFG)-right M1. Finally, we found that neuroactive metabolites, altered microbe and enhanced brain connectivity contributed to the cognitive preservation in NAs. Our findings provide a comprehensive understanding of the microbiota-gut-brain axis in a long-lived population and insights into the establishment of a microbiome and metabolite homeostasis that can benefit human longevity and cognition by enhancing functional brain connectivity.

RCOR1 is targeted by miR-23b-3p to modulate growth, colony formation, migration, and invasion of prostate cancer cells.

OBJECTIVES: Prostate cancer holds the second-highest incidence rate among all male malignancies, with a noticeable scarcity of effective treatment approaches. The REST Corepressor 1 (RCOR1) protein exhibits elevated expression across various tumors, acting as an oncogene. Nevertheless, its functions and mechanisms in prostate cancer have yet to be documented. While miR-23 demonstrates reduced expression in prostate cancer, the downstream genes it regulates remain unclear. METHODS: RT-qPCR and Western blotting assays were utilized to elucidate the mRNA and protein levels of miR-23b-3p and RCOR1. The luciferase reporter assay was employed to unveil the targeting relationship between miR-23b-3p and RCOR1. Additionally, a CCK-8 assay demonstrated cell growth, while colony formation and Transwell assays were performed to observe clone formation, cell migration, and invasion. RESULTS: In this study, we observed substantial mRNA and protein levels of RCOR1 in prostate cancer cells such as DU145, PC3, and LNCap. RCOR1 overexpression enhanced the growth, colony formation, migration, and invasion of prostate cancer cells, whereas genetic silencing of RCOR1 suppressed these processes. Bioinformatics analysis identified miR-23b-3p as a potential regulator of RCOR1, and luciferase assays validated RCOR1 as a downstream target of miR-23b-3p. Increasing miR-23b-3p mimics diminished RCOR1's mRNA and protein levels, while raising miR-23b-3p levels boosted RCOR1's expression. Moreover, the stimulatory impact of RCOR1 on prostate cancer cell development could be countered by elevating miR-23b-3p mimics. CONCLUSION: In summary, our findings confirm that RCOR1 is indeed under the influence of miR-23, shedding light on the miR-23/RCOR1 pathway's role in prostate cancer development. This offers novel theoretical and experimental support for comprehending the underlying mechanisms of prostate cancer and for targeted therapeutic avenues.

Dupliumab therapy for alopecia areata: a case series and review of the literature.

BACKGROUND: A growing body of research supports the important role of the TH2 axis in alopecia areata (AA). Dupilumab is a humanized monoclonal antibody against IL-4Rα that downregulates TH2 response. Although efficacy has been shown in clinical trials, real-world data on the use of dupilumab in AA patients is limited. OBJECTIVES: To report on a case series of 10 patients with AA who were treated with dupilumab and provide real-world evidence regarding its efficacy in treating severe AA. METHODS: In this retrospective single-center study, all AA patients treated with dupilumab treatment were included between May 2022 and October 2023. Clinical outcome measures (Severity of Alopecia Tool, SALT) and adverse events (AEs) were analyzed. In addition, a literature review was conducted to summarize the efficacy of AA with dupilumab and the characteristics of patients previously reported in the literature. RESULTS: We identified 10 patients with AA who were or are being treated with dupilumab, with a median (range) treatment duration of 8 (3-15) months. Of these, four patients have high serum immunoglobulin E (IgE) levels (≥200IU/ml). The mean (IQR) pretreatment SALT score was 79% (52-100). Seven of 10 patients achieved at least 50% re-growth. Of those who improved, the mean (IQR) percentage change in SALT score at 3 months and the end of follow-up was 57% (29%-89%) and 95% (68-100), respectively. Notably, seven patients (70%) had white hair regrowth, with the white hair slowly decreasing over time and the proportion of pigmented black hair increasing. Dupilumab was well tolerated by all patients. No adverse events were reported. CONCLUSIONS: Overall, our research supports dupilumab as another candidate that possesses potential benefits for AA. High levels of IgE may be not prerequisites for dupilumab's successful treatment response.

Hematological parameters as diagnostic biomarkers for patients with rosacea.

Rosacea is a chronic inflammatory skin disease. Systemic inflammation plays a vital role in the pathogenesis of rosacea. Many studies have reported hematological parameters as biomarkers for diseases with inflammatory processes. However, the diagnostic value of hematological parameters in rosacea remains a puzzle. This study involved 462 patients with rosacea, including erythematotelangiectatic rosacea (ETR, n = 179), papulopustular rosacea (PPR, n = 250), and phymatous rosacea (PhR, n = 33), and 924 healthy control subjects. Demographic, clinical, and laboratory information was collected and compared between rosacea subtypes. The hematological parameters of the patients and the healthy controls were compared retrospectively. The platelet volume (MPV) and platelet crit (PCT) were significantly upregulated, and the lower red cell distribution width (RDW) was significantly downregulated in rosacea compared to healthy controls, and they were identified as the diagnostic biomarkers for rosacea with area under the curve values of 0.828, 0.742, and 0.787, respectively. Comparing the hematological parameters among the three rosacea subtypes, we found that platelet-to-lymphocyte ratio and platelet-to-neutrophil ratio values in the ETR group were significantly higher than those in the PPR and PhR groups. The correlation between hematological parameters and clinical scores showed that RDW was negatively correlated with the Clinician Erythema Assessment score. However, there was no significant correlation between the Investigator Global Assessment score and hematological parameters. In conclusion, PCT, MPV, and RDW have diagnostic value for rosacea, and RDW is correlated with the severity of rosacea erythema, implying the potential applications of PCT, MPV, and RDW in the diagnosis and monitoring of rosacea.

Clinical characteristics of the well-defined upper eyelid vascular network pattern in patients with rosacea.

BACKGROUND: Rosacea is a chronic inflammatory skin disease. The diagnosis is based on the symptoms and physical signs, which still lacks objective laboratory tests or imaging tests. OBJECTIVES: To propose and evaluate the upper eyelid network pattern in rosacea. METHODS: Participants included patients diagnosed with rosacea, other facial erythematous skin diseases, and normal controls, all of whom underwent full-face imaging utilizing the VISIA® system software. According to these images, researchers evaluated the condition of the upper eyelid vascular network, developed the grading scale and then compared the difference of distribution in the three groups. RESULTS: The occurrence rate of upper eyelid vascular network in rosacea was significantly higher than that in other facial erythematous skin diseases (84.3 vs. 32.0%, P < 0.001) and normal controls (84.3 vs. 28.0%, P < 0.001). The upper eyelid vascular network pattern was proposed (none [no clearly reticular vessels], mild [10-50% area of reticular vessels], moderate-to-severe [>50% area of reticular vessels]). Moderate-to-severe grade was defined as well-defined upper eyelid vascular network pattern, which was specific to patients with rosacea (rosacea vs. other facial erythematous skin diseases, adjusted odds ratio [aOR] = 5.814, 95% confidence interval [CI]: 3.899-8.670) (rosacea vs. heathy controls, aOR = 12.628, 95% CI: 8.334-19.112). The severity of the well-defined pattern had no significant association with age, duration, and phenotypes of rosacea (P > 0.05). CONCLUSION: The well-defined upper eyelid vascular network pattern specifically appeared in patients with rosacea, which could be a possible clue to the diagnosis of rosacea.

First Report of 16SrII Group Related Phytoplasma Associated with Witches'-broom Disease on Cowpea (Vigna unguiculata) in Hainan Province, China.

Cowpea (Vigna unguiculata L.), a significant vegetable crop in China, holds particular prominence in the tropical island of Hainan. This region serves as the primary production area for the winter cultivation of cowpea. Phytoplasmas are an idiopathic parasitic pathogen and cannot be cultured in vitro. It is mainly transmitted by the insect vectors with the piercing and sucking mouthparts, such as leafhoppers, plant hoppers, and psyllids. (Kumari et al. 2019). On September 11, 2023, typical characteristics of phytoplasma diseases on cowpeas were observed in the experimental base of Hainan Academy of Agricultural Sciences (20°0'38.6964″N, 110°21'35.4024″E, Haikou City, Hainan Province, China), including reduced leaf size, chlorosis, and the development of broom-like branch deformities reminiscent, as depicted in Figure 1. At the same time, we found a large number of leafhoppers near the diseased plants, and we speculated that leafhoppers are the insect carriers that spread the disease. Following an on-site investigation, it was determined that the disease incidence ranges from 10% to 15%, leading to a consequential decrease of about 10% in yield, which is a potential disease that seriously threatens the cowpea industry in Hainan. Ten disease and healthy samples were meticulously collected and subsequently preserved at -80°C within the laboratory refrigerator. Three disease samples denoted as HNNKY-1, HNNKY-2, and HNNKY-3, were randomly chosen, and total DNA extraction was carried out employing the NuClean Plant Genomic DNA Kit (CWBIO, Taizhou, China), while three healthy samples were randomly selected as control. The 16S rRNA gene was amplified by PCR using the primer pairs P1/P7 (Schneider et al. 1995) and R16F2n / R16R2 (Lee et al. 1993) and the secA gene was amplified by PCR using the primer pairs secAfor1/secArev3 (Hodgetts et al. 2008). After agarose gel electrophoresis analysis, no DNA fragments were observed in the healthy leaf samples, whereas all three disease samples yielded amplification products. The PCR products were subsequently sequenced by Hainan Nanshan Biotech Co., Ltd., Haikou, China. After sequence analysis, it was found that the 16S rRNA gene and secA gene sequences HNNKY-1, HNNKY-2, and HNNKY-3 were identical to each other. We selected two gene sequences of strain HNNKY-3 to submission to the GenBank database, The length of the 16S rRNA gene sequence is 1193 base pairs, identified by the accession number OR666421, while the secA gene sequence is 825 base pairs in length, associated with the accession number OR661282. The phytoplasma strain HNNKY-3 was named 'Vigna unguiculata' witches'-broom phytoplasma. A BLAST analysis of the 16S rRNA gene revealed that strain HNNKY-3 displayed a 100% sequence match with 'Emilia sonchifolia' witches'-broom phytoplasma (MT420682), Peanut witches'-broom phytoplasma (OR239773), and 'Raphanus sativus' witches'-broom phytoplasma (OK491387). All of these phytoplasmas were classified within the 16SrII group. Based on the BLAST analysis of partial secA gene sequences, it was discerned that sequence homogeneity ranged from 99.27% to 99.74% among the studied sequences. These sequences were collectively classified as members of the 16SrII group. In addition, a phylogenetic tree was constructed by MEGA 11 (version 11.0.13) based on the 16Sr RNA gene and secA gene by the neighbor-joining method (Tamura et al. 2004). The results demonstrated the clustering of HNNKY-3 phytoplasma strains within the 16SrII group, as illustrated in Figures 2 and 3. A virtual RFLP analysis based on the 16S rRNA gene fragment of HNNKY-3 was conducted using the interactive online phytoplasma classification tool, iPhyClassifier (Zhao et al. 2009). The results indicated that the phytoplasma strain was the same as the reference pattern of the onion yellows phytoplasma of 16SrII-A (GenBank accession: L33765), and the similarity coefficient was 1.00. To best of our knowledge, this is the inaugural documentation of 16SrII Group-related phytoplasma infecting cowpea in Hainan, China, and lays the groundwork for further research on the dissemination of cowpea phytoplasma disease within China.

Design, Synthesis, and Biological Investigations of Novel Carbamoylguanidinyl Nitrobenzoxadiazoles against Chitinolytic Enzymes.

Chitinase has been identified as an important target for insecticides. In this study, a series of novel chitinase inhibitors was designed and synthesized with nitrobenzoxadiazoles. Compound 8d, which contains the N-methylcarbamoylguanidinyl, exhibited high enzyme inhibitory activity and achieved nanomolar inhibition against OfChtI (IC50 = 12.3 nM). Delightfully, it was also found to possess significant inhibitory activity against OfHex1 (IC50 = 1.76 µM). The computational simulation results indicated that compound 8d interacted with OfChtI and OfHex1 in similar modes through hydrogen bonds and hydrophobic and π-π interactions. Insecticidal activity studies revealed that compound 8d showed high mortality against the Lepidoptera Plutella xylostella (mortality rate = 81%) at 200 mg/L. Toxicity studies indicated that compound 8d exhibited negligible toxicity to the natural enemy Trichogramma ostriniae. These results indicate that compound 8d may be a promising candidate for the development of environmentally friendly chitinase inhibitors. Moreover, this study provides a new angle for the design of innovative inhibitors of chitinolytic enzymes.

Discovery of Potent N-Methylcarbamoylguanidino Insect Growth Regulators Targeting OfChtI and OfChi-h.

Insect growth regulators (IGRs) are important insecticides that reduce the harm caused by insects to crops by controlling pest population growth. Chitinases are closely associated with insect growth and are among the most important glycoside hydrolases. Thus, Chitinase is an attractive target for the development of novel insecticides. In this study, we designed and synthesized a series of novel and highly potent insecticides targeting OfChtI and OfChi-h in insects. Enzymatic activity tests showed that most compounds exhibited a potent inhibitory activity against OfCh-h. Binding mode analysis revealed that the target compounds bound to the -1 active subsite of Chitinase through the key pharmacophore N-methylcarbamoylguanidino. Compounds 6e, 6g, 6j, and 6o significantly affected the growth and development of Plutella xylostella at 200 mg/L. Our study provides novel insights for the development of potent insecticide-targeted Chitinase combinations based on receptors and ligands.

Whole genome sequencing identifies genetic variants associated with neurogenic inflammation in rosacea.

Rosacea is a chronic inflammatory skin disorder with high incidence rate. Although genetic predisposition to rosacea is suggested by existing evidence, the genetic basis remains largely unknown. Here we present the integrated results of whole genome sequencing (WGS) in 3 large rosacea families and whole exome sequencing (WES) in 49 additional validation families. We identify single rare deleterious variants of LRRC4, SH3PXD2A and SLC26A8 in large families, respectively. The relevance of SH3PXD2A, SLC26A8 and LRR family genes in rosacea predisposition is underscored by presence of additional variants in independent families. Gene ontology analysis suggests that these genes encode proteins taking part in neural synaptic processes and cell adhesion. In vitro functional analysis shows that mutations in LRRC4, SH3PXD2A and SLC26A8 induce the production of vasoactive neuropeptides in human neural cells. In a mouse model recapitulating a recurrent Lrrc4 mutation from human patients, we find rosacea-like skin inflammation, underpinned by excessive vasoactive intestinal peptide (VIP) release by peripheral neurons. These findings strongly support familial inheritance and neurogenic inflammation in rosacea development and provide mechanistic insight into the etiopathogenesis of the condition.

Efficacy and safety of antibiotic agents in the treatment of rosacea: a systemic network meta-analysis.

Background: Antibiotics are considered the backbone of rosacea management, especially for controlling inflammatory papules and pustules. We aim to evaluate the efficacy and safety of varied prescriptions and doses of antibiotics in treating rosacea by network meta-analysis. Methods: In this study, we compared all available randomized controlled trials (RCTs) that have studied systemic and topical antibiotics and placebo in rosacea therapy. We searched databases such as the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PubMed, Web of Science, and LILACS for published and unpublished RCTs on ClinicalTrials.gov before April 2023. The primary outcome was the improvement of the Investigator's Global Assessment (IGA) scores, and the secondary outcomes consisted of the improvement of the Patient's Global Assessment (PaGA) scores, Clinician's Erythema Assessment (CEA) scores, and adverse events (AEs). We used Bayesian random effects models for multiple treatment comparisons. Results: We identified 1,703 results through these databases. Thirty-one randomized trials with 8,226 patients were included. The heterogeneity and inconsistency between the trials were low, with a low risk of bias of all trials. Oral doxycycline 40 mg, minocycline 100 mg, and minocycline 40 mg, as well as topical ivermectin and metronidazole 0.75%, were effective in treating papules and pustules, thereby decreasing IGA in rosacea. Among these, minocycline 100 mg ranked top in efficacy. As for improving the PaGA scores, topical ivermectin, metronidazole 1%, and systemic oxytetracycline were effective, of which oxytetracycline worked the best. Both doxycycline 40 mg and metronidazole 0.75% presented no therapeutic effect for erythema. Considering the safety of the agents, systemic application of azithromycin and doxycycline 100 mg significantly increase the risk of AEs. Conclusion: Our review suggests that a high dosage of systemic minocycline is the most effective in treating rosacea phenotypes with papules and pustules with a low risk of AEs. However, there were no sufficient evidence-based data in exploring the influence of antibiotics on erythema. The phenotype of rosacea should be taken into consideration along with benefit and safety when making prescriptions due to AEs. Clinical Trial Registration: NCT(2016): http://cochranelibrary-wiley.com/o/cochrane/clcentral/articles/962/CN-01506962/frame.html NCT(2017): http://cochranelibrary-wiley.com/o/cochrane/clcentral/articles/764/CN-01565764/frame.html.

Local vs Systemic Use of Steroids for Sudden Deafness with Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND: Diabetes is associated with a risk of idiopathic sudden deafness. The main treatment of diabetic sudden deafness is systemic and topical application of steroids. Topical steroid therapy reduces systemic adverse reactions compared with systemic therapy. PURPOSE: The aim of this study was to conduct a meta-analysis design on the improvement value and recovery rate of pure tone mean hearing threshold (PTA).To investigate whether there is difference between local and systemic steroid treatment as the initial treatment for sudden deafness patients with diabetes. METHODS: We searched databases from publication date to October 1, 2022 including PubMed, EMBASE, Cochrane Library, web of science, CNKI, Wan fang Database, China Biomedical Literature Database (CBM), and VIP information resource system. A systematic literature review was conducted on the efficacy and safety of local and systemic steroid therapy for diabetic sudden deafness. RevMan5.4 and stata14 software were used for Meta-analysis. RESULTS: A total of 23 studies were included in this study, covering 1777 patients, including 885 cases in the observation group (local steroid group) and 894 cases in the control group (systemic steroid group). Meta-analysis showed that there was a significant difference in the total effective rate of local and systemic steroid treatment for diabetic sudden deafness between groups (RR = 1.17, 95% CI = 1.11-1.22, P < 0.05). The effective rate in the observation group was higher than that in the control group. For the improvement of PTA, the difference between groups was statistically significant (RR = 6.60, 95% CI = 3.07-10.14, P < 0.05). The improvement of PTA in the local steroid group was higher than that in the systemic steroid group. Subgroup analysis showed that there were significant differences between groups in hormones, drug administration, follow-up time and course of disease. CONCLUSION: Topical steroid therapy is effective in the treatment of diabetic sudden deafness. Hormone methylprednisolone has high effective rate; the shorter the course of disease and the longer the follow-up time are, the higher the total effective rate will be. Tympanic injection is more effective than post-aural injection. Topical steroid injections are safer for hormonal side effect.

Unexpected Behavior in Thermal Conductivity of Confined Monolayer Water.

Monolayer water can be formed under extreme confinement and will present distinctive thermodynamic properties compared with bulk water. In this work, we perform molecular dynamics simulations to study the thermal conductivity of monolayer water confined in graphene channels, finding an unexpected way of thermal conductivity of monolayer water dependent on its number density, which has a close correlation with the structure of water. The monolayer water is in an amorphous state, and its thermal conductivity increases linearly with the area density when the water density is low at first. Then, the thermal conductivity increases as the number density of water rises, which is attributed to the formation of a crystal structure and the reduction of crystal defects as the number of water molecules increases. After reaching the zenith, the thermal conductivity decreases rapidly owing to the formation of a wrinkle structure of monolayer water with excessive water molecules, which weakens the phonon dispersion. Moreover, we further investigate the remarkable effects of the channel height on both the structure and thermal conductivity of monolayer water. In summary, this study demonstrates the close connection between the thermal conductivity of monolayer water and its structure, contributing to not only expanding the understanding of the thermodynamic property of nanoconfined water but also benefiting the engineering applications for nanofluidics.

SMPD1 expression profile and mutation landscape help decipher genotype-phenotype association and precision diagnosis for acid sphingomyelinase deficiency.

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) disorder, also known as Niemann-Pick disease (NPD) is a rare genetic disease caused by mutations in SMPD1 gene, which encodes sphingomyelin phosphodiesterase (ASM). Except for liver and spleen enlargement and lung disease, two subtypes (Type A and B) of NDP have different onset times, survival times, ASM activities, and neurological abnormalities. To comprehensively explore NPD's genotype-phenotype association and pathophysiological characteristics, we collected 144 NPD cases with strict quality control through literature mining. RESULTS: The difference in ASM activity can differentiate NPD type A from other subtypes, with the ratio of ASM activity to the reference values being lower in type A (threshold 0.045 (4.45%)). Severe variations, such as deletion and insertion, can cause complete loss of ASM function, leading to type A, whereas relatively mild missense mutations generally result in type B. Among reported mutations, the p.Arg3AlafsX76 mutation is highly prevalent in the Chinese population, and the p.R608del mutation is common in Mediterranean countries. The expression profiles of SMPD1 from GTEx and single-cell RNA sequencing data of multiple fetal tissues showed that high expressions of SMPD1 can be observed in the liver, spleen, and brain tissues of adults and hepatoblasts, hematopoietic stem cells, STC2_TLX1-positive cells, mesothelial cells of the spleen, vascular endothelial cells of the cerebellum and the cerebrum of fetuses, indicating that SMPD1 dysfunction is highly likely to have a significant effect on the function of those cell types during development and the clinicians need pay attention to these organs or tissues as well during diagnosis. In addition, we also predicted 21 new pathogenic mutations in the SMPD1 gene that potentially cause the NPD, signifying that more rare cases will be detected with those mutations in SMPD1. Finally, we also analysed the function of the NPD type A cells following the extracellular milieu. CONCLUSIONS: Our study is the first to elucidate the effects of SMPD1 mutation on cell types and at the tissue level, which provides new insights into the genotype-phenotype association and can help in the precise diagnosis of NPD.

Multidimensional evaluation of offline and online education in dermatology teaching during the COVID-19 pandemic in a chinese teaching hospital: a cross-sectional study.

BACKGROUND: The global spread of Coronavirus disease (COVID-19) has led to the use of online teaching methods in universities, but the effect of online education on dermatology teaching remains unclear. METHODS: We designed a multi-dimensional teaching evaluation form for data collection, student teaching feedback evaluation, and assessed the scores of final theoretical and clinical skill tests, to compare the effective difference between online and offline teaching of dermatology. RESULTS: A total of 311 valid questionnaires of medical undergraduates were collected, 116 of which were enrolled for offline learning, and 195 for online learning. The average score of final theoretical test in the online teaching group had no significant difference compared with that in the offline teaching group (75.33 ± 7.37 vs.75.63 ± 7.51, P = 0.734). However, both scores of skin lesion recognition test and medical history collection test in the online teaching group were significantly lower than that in the offline teaching group (6.53 ± 0.86 vs. 7.10 ± 1.11, P < 0.001; 6.70 ± 1.16 vs. 7.62 ± 0.85, P < 0.001). Additionally, the scores of understanding skin lesions in the online teaching group were significantly lower than that in the offline group (P < 0.001), and the scores of overall understanding of skin diseases and evaluating their learning mode in the online teaching group also decreased (P < 0.05). Among the 195 students enrolled in the online learning group, 156 students (80.0%) recognized that the time of offline teaching should be increased. CONCLUSIONS: Both online and offline education can be used in dermatology theory teaching, but online education is less efficient in skin lesion and practical skills learning. More online teaching software with skin diseases characteristic should be developed to improve the online teaching effect.

Preparation of a Tetra-Imidazolium Salt and Sensing for p-Dinitrobenzene.

A macrocyclic tetra-imidazolium salt (2) based on quinoxaline was prepared and characterized. The recognition of 2 to nitro compounds was investigated by fluorescence spectroscopy, 1H NMR titrations, MS, IR spectroscopy, and UV/vis spectroscopy. The results displayed that 2 was able to effectively differentiate p-dinitrobenzene from other nitro compounds via the fluorescence method.

Rational Design of N-Methylcarbamoylguanidinyl Derivatives as Highly Potent Dual-Target Chitin Hydrolase Inhibitors for Retarding Growth of Pest Insects.

Chitin degradation is a vital process for the growth of insects. Chitin hydrolase OfChtI and ß-N-acetylhexosaminidase OfHex1 are two key enzymes involved in hydrolyzing the chitin of insects' cuticles. Thus, they are considered promising targets for preventing and controlling agricultural pests. In this study, we designed and synthesized a series of compounds bearing N-methylcarbamoylguanidinyl and N-methoxycarbonylguanidinyl as dual-target inhibitors of OfChtI and OfHex1. The most potent dual-target inhibitor, compound 10d, exhibited half-maximal inhibitory concentration (IC50) values of 27.1 and 249.1 nM against OfChtI and OfHex1, respectively. Furthermore, the insecticidal activity studies showed that compounds 10a-c, 10k, and 10l bear significant effects on the growth and development of Plutella xylostella. This work provides a promising method for the development of novel chitin hydrolase inhibitors as potential pest control and management agents.