Case report: Rubella virus-associated cutaneous granuloma in an adult with TAP1 deficiency.

Rubella virus-associated granulomas commonly occur in immunocompromised individuals, exhibiting a diverse range of clinical presentations. These manifestations can vary from predominantly superficial cutaneous plaques or nonulcerative nodules to more severe deep ulcerative lesions, often accompanied by extensive necrosis and significant tissue destruction. TAP1 deficiency, an exceedingly rare primary immune-deficiency disorder, presents with severe chronic sino-pulmonary infection and cutaneous granulomas. This report highlights the occurrence of rubella virus-associated cutaneous granulomas in patients with TAP1 deficiency. Notably, the pathogenic mutation responsible for TAP1 deficiency stems from a novel genetic alteration that has not been previously reported. This novel observation holds potential significance for the field of diagnosis and investigative efforts in the context of immunodeficiency disorders.

Toxic epidermal necrolysis complicated with primary cutaneous aspergillosis: A report of four cases.

Primary cutaneous aspergillosis (PCA) is a rare opportunistic infection caused by Aspergillus that can be life-threatening. PCA is mainly reported in immunocompromised hosts such as patients with AIDS, those with hematologic malignancy, or infants with occlusive dressings. However, no study has previously reported PCA associated with toxic epidermal necrolysis (TEN). This study reports four cases of TEN complicated with PCA, presenting with discrete gray or black spots over newly formed epithelia. Risk factors of PCA in patients with TEN include host factors, iatrogenic factors, indoor environment, and wound care. Two of the four cases eventually died, highlighting the importance of further exploring PCA in patients with TEN.

Galleria mellonella in vitro model for chromoblastomycosis shows large differences in virulence between isolates.

BACKGROUND: Chromoblastomycosis is the World Health Organization (WHO)-recognized fungal implantation disease that eventually leads to severe mutilation. Cladophialophora carrionii (C. carrionii) is one of the agents. However, the pathogenesis of C. carrionii is not fully investigated yet. METHODS: We investigated the pathogenic potential of the fungus in a Galleria mellonella (G. mellonella) larvae infection model. Six strains of C. carrionii, and three of its environmental relative C. yegresii were tested. The G. mellonella model was also applied to determine antifungal efficacy of amphotericin B, itraconazole, voriconazole, posaconazole, and terbinafine. RESULTS: All strains were able to infect the larvae, but virulence potentials were strain-specific and showed no correlation with clinical background of the respective isolate. Survival of larvae also varied with infection dose, and with growth speed and melanization of the fungus. Posaconazole and voriconazole exhibited best activity against Cladophialophora, followed by itraconazole and terbinafine, while limited efficacy was seen for amphotericin B. CONCLUSION: Infection behavior deviates significantly between strains. In vitro antifungal susceptibility of tested strains only partly explained the limited treatment efficacy in vivo.

The in vitro Activity of Echinocandins Against Clinical Trichophyton rubrum Isolates and Review of the Susceptibility of T. rubrum to Echinocandins Worldwide.

Introduction: The emergence of resistance in Trichophyton rubrum to azoles and terbinafine has become increasingly evident in recent years, necessitating the development of novel antifungal drugs and the exploration of new indications for existing agents. Methods: In this study, we retrospectively evaluated the in vitro antifungal activity of 3 echinocandins (anidulafungin, caspofungin, and micafungin) against 73 clinical isolates of T. rubrum collected from a teaching hospital in Shanghai, China, using EUCAST E.DEF 9.3.1 with minor modification. We also reviewed the susceptibility of T. rubrum to echinocandins globally by literature searching. Results: Our findings revealed that micafungin exhibited the lowest modal minimum effective concentration (MEC) value (0.08 mg/L, n = 28) and the lowest geometric mean (GM) MEC value (0.014 mg/L) among the 73 isolates of T. rubrum tested, followed by anidulafungin with a modal MEC value of 0.016 mg/L (n = 67) and a GM of 0.018 mg/L. Caspofungin displayed a higher modal MEC value of 0.5 mg/L (n = 35) and a GM of 0.308 mg/L. Despite variations in methodologies, similar results were obtained from the review of five relevant studies included in our analysis. Discussion: Echinocandins exhibited excellent in vitro activity against T. rubrum isolates, with micafungin and anidulafungin demonstrating greater potency than caspofungin. These findings suggest that echinocandins could be considered as potential treatment options for managing recalcitrant dermatophytoses resulting from the emergence of resistance. However, it is important to note that the clinical efficacy of these in vitro findings has yet to be established and warrants further investigation.

Efficacy and associated neurotransmitters of digital cognitive behavior therapy for atopic dermatitis: A comparative effectiveness research.

BACKGROUND: Negative emotions are a major comorbidity of atopic dermatitis (AD). Evidence that supports the effectiveness of digital cognitive behavioral therapy (dCBT) as an adjuvant therapy for AD remains limited. OBJECTIVE: To investigate the preliminary efficacy of additional dCBT and potential neurotransmitter biomarkers for AD accompanied by negative emotions. METHODS: Thirty-two patients with AD were recruited and examined for clinical severity and negative emotions including insomnia, anxiety, and depression. Patients with mild-to-moderate negative emotions were divided into two groups that received standard care (N = 9) or mobile app-delivered CBT plus standard care (N = 11) for 12 weeks. Plasma levels of 40 neurotransmitters were determined using liquid chromatography tandem mass spectrometry pre- and post-treatment. RESULTS: Skin lesions, itch, and insomnia were significantly improved in both treatment groups. Improvements of itch (P = 0.0449) and insomnia (P = 0.0089) were more robust in the combination treatment group than those in the standard treatment group. Neurotransmitters that involve tryptophan, dopamine, and histidine pathways were markedly altered in patients with AD compared with healthy controls. Taurine levels were selectively increased following dCBT plus standard care (P = 0.0259). Baseline levels of L-tyrosine were negatively correlated with the reduction of skin lesions (r = -0.9073, P = 0.0334) and itch intensity (r = -0.9322, P = 0.0210) in the combination therapy group. CONCLUSIONS: dCBT provides an efficacious supplementary approach for AD accompanied by negative emotions. Emotion-related neurotransmitters may contribute to AD and serve as indicators for treatment effects.

Prognostic value of L4 lymph node dissection during video-assisted thoracoscopic surgery in patients with left-sided non-small cell lung cancer: a single-center, retrospective cohort study.

Background: Lymph node dissection (LND) is crucial procedure during radical resection of non-small cell lung cancer (NSCLC), but the prognostic value of L4 LND remains elusive. To investigate the prognostic value of L4 LND in patients with left-side NSCLC who underwent video-assisted thoracoscopic surgery (VATS). Methods: Three hundred twelve patients who underwent VATS between Jan. 2007 and Dec. 2016 were reviewed. Of those, 119 underwent L4 LND (L4D+), whereas the other 193 patients did not (L4D-). The inclusion criteria were as follows: patients diagnosed with primary left-sided NSCLC who underwent VATS lobectomy combined with LND; patients subjected to R0 resection and tumor pathological stage T1-4N0-2M0. The primary endpoint was overall survival (OS). OS was calculated from the operation date to the date of death. The chi-square test was used for categorical variables, and a t test was used for continuous variables. Results: A total of 119 patients underwent L4 LND, and the procedure was more likely to be performed on upper lobe tumors (P=0.019). Patient distributions with respect to age, gender, smoking history, clinical stage, adjuvant therapy, tumor differentiation and tumor size were well balanced between two groups. More lymph nodes (LNs) were dissected in the L4D+ group than in the L4D- group (P<0.001). The rate of metastasis to L4 lymph nodes was 9.2%, which was comparable between patients with upper and lower lobe tumors (8.9% vs. 10.0%, P=1.000). The L4D+ group exhibited a significantly better OS than the L4D- group (median OS: undefined vs. 130 months, HR 0.47; 95% CI: 0.31-0.72; P=0.002). Multivariate analysis showed that L4 LND was an independent factor for OS. However, OS did not significantly differ between the two groups of cT1aN0 and cT1bN0 patients (OS: HR 0.44; 95% CI: 0.18-1.06; P=0.12). Conclusions: L4 LND is recommended for patients with left-sided NSCLC as an essential component of radical resection. The role of L4 LND in cT1a-bN0 disease warrants further study.

Potency of olorofim (F901318) compared to contemporary antifungal agents against clinical Aspergillus fumigatus isolates, and review of azole resistance phenotype and genotype epidemiology in China.

Triazole resistance in A. fumigatus is an increasing worldwide problem that causes major challenges in the management of aspergillosis. New antifungal drugs are needed with novel targets, that are effective in triazole-resistant infection. In this study, we retrospectively evaluated potency of the novel drug olorofim compared to contemporary antifungal agents against 111 clinical A. fumigatus isolates collected from Huashan Hospital, Shanghai, China, using EUCAST methodology, and reviewed the literature on triazole resistant A. fumigatus published between 1966 and 2020 in China. Olorofim was active in vitro against all tested A. fumigatus isolates with MIC90 of 0.031mg/L (range 0.008-0.062 mg/L). For 4 triazole-resistant A. fumigatus (TRAF) isolates, the olorofim MIC ranged between 0.016-0.062mg/L. The reported rates of TRAF in China is 2.5% - 5.56% for clinical isolates, and 0-1.4% for environmental isolates.TR34/L98H/S297T/F495I is the predominant resistance mechanism, followed by TR34/L98H. Non TR-mediated TRAF isolates, mostly harboring a cyp51A single point mutation, showed greater genetic diversity than TR-mediated resistant isolates. Resistance due toTR34/L98H and TR34/L98H/S297T/F495I mutations among TRAF isolates might have evolved from separate local isolates in China. Continuous isolation of TRAF in China underscores the need for systematic resistance surveillance as well as the need for novel drug targets such as olorofim.

Two new triterpene glycosides with antiproliferative activities on HepG2 from Phytolacca acinosa fruit fermentation broth.

Two new oleanane-type triterpene glycosides, phytolasides A (1) and B (2), and six known ones (3-8), were isolated from Phytolacca acinosa fruit fermentation broth. Their structures were elucidated by HR-ESI-MS and 1 D- and 2 D-NMR spectroscopic methods. Antiproliferation of compounds 1 and 2 against HepG2 cells was examined by using CCK8 assays.

HIF1-α upregulation induces proinflammatory factors to boost host killing capacity after Aspergillus fumigatus exposure.

Aims: HIF1-α is an important transcription factor in the regulation of the immune response. The protective function of HIF1-α in the host epithelial immune response to Aspergillus fumigatus requires further clarification. Methods: In this study we demonstrated the effect of upregulation of HIF1-α expression in A549 cells and mouse airway cells exposed to A. fumigatus in vivo. Results: The killing capacity was enhanced by boosting proinflammatory factors both in vitro and in vivo. Moreover, airway inflammation was reduced in the HIF1-α-upregulated mice. Conclusion: We identified a protective role for HIF1-α in anti-A. fumigatus immunity. Modulation of HIF1-α might be a target for the development of aspergillosis therapy.

Design, Synthesis, and Biological Evaluation of New 1H-Imidazole-2-Carboxylic Acid Derivatives as Metallo-ß-Lactamase Inhibitors.

As one of important mechanisms to ß-lactam antimicrobial resistance, metallo-ß-lactamases (MBLs) have been receiving increasing worldwide attentions. Ambler subclass B1 MBLs are most clinically relevant, because they can hydrolyze almost all ß-lactams with the exception of monobactams. However, it is still lacking of clinically useful drugs to combat MBL-medicated resistance. We previously identified 1H-imidazole-2-carboxylic acid as a core metal-binding pharmacophore (MBP) to target multiple B1 MBLs. Herein, we report structural optimization of 1H-imidazole-2-carboxylic acid and substituents. Structure-activity relationship (SAR) analyses revealed that replacement of 1H-imidazole-2-carboxylic acid with other structurally highly similar MBPs excepting thiazole-4-carboxylic acid resulted in decreased MBL inhibition. Further SAR studies identified more potent inhibitors to MBLs, of which 28 manifested IC50 values of 0.018 µM for both VIM-2 and VIM-5. The microbiological tests demonstrated that the most tested compounds showed improved synergistic effects; some compounds at 1 µg/ml were able to reduce meropenem MIC by at least 16-fold, which will be worth further development of new potent inhibitors particularly targeting VIM-type MBLs.

Inhibition of tumor necrosis factor improves conventional steroid therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis in a cohort of patients.

BACKGROUND: Systemic steroid therapies for Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have been challenged because of their limited benefits. Whether additional tumor necrosis factor (TNF) α inhibition provides an optimized approach remains unexplored. OBJECTIVE: To investigate the efficacy of TNF-α inhibition combined with a steroid to treat SJS/TEN and to identify potential biomarkers. METHODS: Twenty-five patients with SJS/TEN were recruited and divided into 2 groups: 10 patients received methylprednisolone and 15 patients received etanercept plus methylprednisolone. Serum levels of granzyme B, perforin, interferon-γ, interleukin (IL) 6, IL-15, IL-18, macrophage inflammatory protein 1α, macrophage inflammatory protein 1ß, and TNF-α were measured by multiplex cytokine analysis kits during the acute and resolution phases. RESULTS: Compared with the steroid monotherapy, the combination therapy significantly shortened the course of the initial steroid treatment and the duration of the acute stage, hospitalization stay, and skin re-epithelialization. Although both therapies significantly reduced IL-15 levels; the combination therapy also decreased IL-6 and IL-18 levels. While the level of IL-15 was positively correlated with skin re-epithelialization time in both groups, the level of IL-6 served as an additional marker for the course of the disease in the combination therapy group. LIMITATIONS: The cohort size is relatively small. CONCLUSION: Additional TNF-α inhibition to steroid treatment appeared to improve outcomes for SJS/TEN.

Discovery of new human Sirtuin 5 inhibitors by mimicking glutaryl-lysine substrates.

Human sirtuin 5 (SIRT5) plays pivotal roles in metabolic pathways and other biological processes, and is involved in several human diseases including cancer. Development of new potent and selective SIRT5 inhibitors is currently desirable to provide potential therapeutics for related diseases. Herein, we report a series of new 3-thioureidopropanoic acid derivatives, which were designed to mimic the binding features of SIRT5 glutaryl-lysine substrates. Structure-activity relationship studies revealed several compounds with low micromolar inhibitory activities to SIRT5. Computational and biochemical studies indicated that these compounds exhibited competitive SIRT5 inhibition with respect to the glutaryl-lysine substrate rather than nicotinamide adenine dinucleotide cofactor. Moreover, they showed high selectivity for SIRT5 over SIRT1-3 and 6 and could stabilize SIRT5 proteins as revealed by thermal shift analyses. This work provides an effective substrate-mimicking strategy for future inhibitor design, and offers new inhibitors to investigate their therapeutic potentials in SIRT5-associated disease models.

Majocchi's granuloma: Autoinoculation and adaption of Trichophyton rubrum with molecular evidence.

BACKGROUND: Trichophyton rubrum, an important aetiological agent of superficial dermatophytosis, occasionally penetrates into deeper tissues, causing inflammation and a granulomatous response. Only few case reports of T. rubrum granuloma with molecular evidence for autoinoculation have been published. OBJECTIVES: To find the genetic basis of adaptation to a different microhabitat following autoinoculation of Trichophyton rubrum. METHODS: A case of Majocchi's granuloma is reported, with isolation of T. rubrum strains from foot and chin, respectively. Whole-genome sequencing of the two strains has been performed. Phylogenetic reconstruction and SIFT analysis were conducted. RESULTS: A phenotypic difference has been observed between the two isolates. 20 and 19 indels, 8 and 15 SNVs were found in foot and chin strains, respectively. Foot and chin strains formed a monophyletic group. Two non-synonymous mutations of chin strains were observed in the TERG_06754 gene encoding cytochrome c peroxidase (CCP). The G293C amino acid change in TERG_03373 was predicted to affect protein function significantly. The mutated amino acid (cysteine) was only found in the chin strain in all dermatophyte non-redundant sequences. CONCLUSIONS: Non-synonymous mutations located in TERG_06754 and TERG_03373 were predicted to affect protein functions, which may facilitate the adaption for invasion of the superficial cutaneous strain. As the different living environments of these two strains (oxygenous, lower-temperature for the pedal strain; hypoxia, higher-temperature for the chin strain), a stratum corneum-to-dermal adaption hypothesis of T. rubrum was proposed.

[Study on mechanism of Phytolaccae Radix and its split components based on network pharmacology].

This paper aimed to explore the mechanism of the split components of Phytolaccae Radix by means of network pharmaco-logy. Based on the theoretical hypothesis of the nature and taste of traditional Chinese medicine, the chemical components of the separated components of Phytolaccae Radix were selected by using Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and Traditional Chinese Medicines IntegratedDatabase(TCMID) databases in combination with related literatures. Relevant target analysis was carried out based on PubChem and SwissTargetPrediction databases. Targets corresponding to disease were excavated based on GeneCards for each split component, corresponding potential targets were obtained through mapping the target set of target compounds to disease targets. GO biological process analysis and KEGG pathway enrichment analysis were performed on the mapped targets with the help of DAVID database. Based on Cytoscape software and the corresponding efficacy, the network diagram of "medicinal material-split components-compound-target-pathway" was constructed to explore the mechanism of different efficacy of the separated components of Cytoscape. And the target purgation and diuretic mapping was used as the target of the traditional efficacy of smoothening secretion for the first time. The study explored esculentoside component, fatty oil component and phenolic acid component, a total of 30 target compounds and 301 corresponding targets, involving 44 potential targets for "anti-inflammatory", 50 potential targets for "immunoregulation", 52 potential targets for "smoothening secretion", 28 potential targets for "antibacterial activity", 28 potential targets for "antiviral effect", and 29 potential targets for "antitumor effect". Topological analysis revealed 14 key gene targets such as MAPK8, MAPK14, EGFR and PTGS2. A total of 684 GO entries and 235 KEGG pathways were obtained through bioinformatics enrichment analysis, mainly involving TNF signaling pathway, NF-kappaB signaling pathway and MAPK signaling pathway. This study revealed the multi-component, multi-target, and multi-channel action mechanism of the split components of Phytolaccae Radix, which provided certain basis for the next step to clarify the split components of Phytolaccae Radix through the method of system biology, and injected new content and significance into the study of properties and flavors theory.

Daturataturin A, a withanolide in Datura metel L., induces HaCaT autophagy through the PI3K-Akt-mTOR signaling pathway.

Daturataturin A (DTA), a withanolide compound in Datura metel L., exhibits excellent anti-inflammatory and anti-proliferative activities. Here, we report the study of DTA-induced proliferation and inflammation in human immortalized keratinocytes (HaCaTs) and the associated molecular mechanisms. HaCaTs are a model of the epidermal proliferative state of cells. The pharmacodynamics and mechanism of DTA were studied by western blot, immunofluorescence, apoptosis and proliferation detection, and real-time quantitative polymerase chain reaction. We confirmed that DTA induced HaCaT autophagy, which, in turn, induced HaCaT senescence and, ultimately, led to cell cycle arrest. DTA also negatively regulated inflammation through the activation of autophagy. This may be one of the mechanisms underlying the action of Datura metel L. preparation used for the treatment of psoriasis.

Effect of Hordei Fructus Germinatus on differential gene expression in the prolactin signaling pathway in the mammary gland of lactating rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In China, Hordei Fructus Germinatus (HFG) is the germinated and dried fruit of Hordeum vulgare L, which is commonly used in clinical Chinese medicine. Traditional Chinese Medicine (TCM) theory holds that HFG can be both medicinal and edible, which means that it is derived from food medicine. Raw HFG and roasted HFG are used to treat hypogalactia, hyperprolactinemia and indigestion. In recent years, the lactogenic and galactophygous effects of HFG have attracted increasing attention. Nevertheless, there is much confusion over the use of raw and processed HFG, and the mechanism of its lactogenic effect seems remains poorly understood. AIM OF THE STUDY: This study aimed to explore the lactogenic effect of raw HFG and roasted HFG on rats with overloaded lactation and to reveal the underlying molecular mechanism. MATERIALS AND METHODS: Raw and processed HFG water decoctions were given to overloaded lactation model rats at a dose of 1.7800 g kg-1·d-1, and the control group was given the same volume of water. The lactogenic effect of raw and processed HFG was evaluated by measuring daily lactation, body weight and pup body weight, serum PRL, E2, and GH contents after parturition, and the pathological characteristics of mammary tissue sections. cDNA microarrays can be used to screen diverse gene expression patterns and signaling pathways related to prolactin. The expression of relevant differentially expressed genes was verified by real-time PCR and western blotting. RESULTS: In vivo experiments demonstrated that the raw HFG water decoction stimulated mammogenesis, accelerated the transformation of the lobular acinar system, resulted in denser mammary epithelial cells and thicker glandular ducts that were full of milk and facilitated the secretion of milk. Moreover, HFG increased PRL, E2, and GH levels, pup body weight, daily lactation and the body weight of lactating rats. Following gene chip identification, KEGG pathway enrichment analysis revealed genes that were highly related to prolactin in the prolactin signaling pathway and JAK-STAT signaling pathway, and the main differentially expressed genes were Jak2 (down), Stat5α (up), cyclin D1 (up), SOCS1 (up), CISH (down) and PRLR (up). Compared with the control group, RT-PCR results indicated that Jak2 and CISH were downregulated and that Stat5α, cyclin D1, SOCS1 and PRLR were upregulated. Western blot assays showed that PRLR, STAT5α and cyclin D1 levels in the mammary glands of the raw HFG water decoction group were significantly increased, which was consistent with the results of cDNA microarray screening. CONCLUSION: The present study reveals that raw HFG effectively enhances lactation in rats, possibly by influencing the prolactin/JAK-STAT signaling pathway.

Recent advances in the development of histone deacylase SIRT2 inhibitors.

Sirtuin 2 (SIRT2) is an important and special member of the atypical histone deacetylase Sirtuin (SIRT) family. Due to its extensive catalytic effects, SIRT2 can regulate autophagy, myelination, immunity, inflammation and other physiological processes. Recent evidence revealed that dysregulation of human SIRT2 activity is associated with the pathogenesis and prognosis of cancers, Parkinson's disease and other disorders; thus SIRT2 is a promising target for potential therapeutic intervention. This review presents a systematic summary of nine chemotypes of small-molecule SIRT2 inhibitors, particularly including the discovery and structural optimization strategies, which will be useful for future efforts to develop new inhibitors targeting SIRT2 and associated target proteins.

Kinetic host defense of the mice infected with Aspergillus Fumigatus.

Aim:Aspergillus fumigatus is one of the most common opportunistic fungi that can cause invasive infection. To profile the kinetic variation of immune cells and cytokines after exposure to A. fumigatus thoroughly, we established a pulmonary A. fumigatus infection model in temporarily immunosuppressed mice. Materials & methods: Systematic and kinetic studies of different immune cells and cytokines were performed. Results: We observed that the granulocytes and macrophages recruited to the site of infection played an important role in the infectious phase. There was a significant increase in the cytokines IFN-γ, IL-6, TNF-α as well as the chemokines CXCL1, MIP-1α, MIP-2 and CCL5 after infection. IL-10 was found to participate in balancing the anti-inflammatory response in the recovery phases. The immune response mediated by T cells was mainly presented by the Th1-type on day 7 after exposure with a high proportion of IFN-γ+ CD4+ T cells and CD4+CD44highCD62Llow effector T cells. Conclusion: These kinetic parameters of the immune response might provide diagnostic clues for A. fumigatus infection.

Species Distinction in the Trichophyton rubrum Complex.

The Trichophyton rubrum species complex comprises commonly encountered dermatophytic fungi with a worldwide distribution. The members of the complex usually have distinct phenotypes in culture and cause different clinical symptoms, despite high genome similarity. In order to better delimit the species within the complex, molecular, phenotypic, and physiological characteristics were combined to reestablish a natural species concept. Three groups, T. rubrum, T. soudanense, and T. violaceum, could be distinguished based on the sequence of the internal transcribed spacer (ITS) ribosomal DNA barcode gene. On average, strains within each group were similar by colony appearance, microscopy, and physiology, but strains between groups showed significant differences. Trichophyton rubrum strains had higher keratinase activity, whereas T. violaceum strains tended to be more lipophilic; however, none of the phenotypic features were diagnostic. The results of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and amplified fragment length polymorphism (AFLP) were partially consistent with the ITS data but failed to distinguish the species unambiguously. Despite their close similarity, T. violaceum, T. soudanense, and T. rubrum can be regarded as independent species with distinct geographical distributions and clinical predilections. Trichophyton soudanense is pheno- and genotypically intermediate between T. rubrum and T. violaceum For routine diagnostics, ITS sequencing is recommended.

Crystallographic and SAR analyses reveal the high requirements needed to selectively and potently inhibit SIRT2 deacetylase and decanoylase.

A high-quality X-ray crystal structure reveals the mechanism of compound 1a inhibiting SIRT2 deacetylase and decanoylase. Structure-activity relationship (SAR) analysis of the synthesized derivatives of 1a reveals the high requirements needed for selective inhibitors to bind with the induced hydrophobic pocket and potently inhibit sirtuin 2 deacetylase.