Modeling single cell trajectory using forward-backward stochastic differential equations.

Recent advances in single-cell sequencing technology have provided opportunities for mathematical modeling of dynamic developmental processes at the single-cell level, such as inferring developmental trajectories. Optimal transport has emerged as a promising theoretical framework for this task by computing pairings between cells from different time points. However, optimal transport methods have limitations in capturing nonlinear trajectories, as they are static and can only infer linear paths between endpoints. In contrast, stochastic differential equations (SDEs) offer a dynamic and flexible approach that can model non-linear trajectories, including the shape of the path. Nevertheless, existing SDE methods often rely on numerical approximations that can lead to inaccurate inferences, deviating from true trajectories. To address this challenge, we propose a novel approach combining forward-backward stochastic differential equations (FBSDE) with a refined approximation procedure. Our FBSDE model integrates the forward and backward movements of two SDEs in time, aiming to capture the underlying dynamics of single-cell developmental trajectories. Through comprehensive benchmarking on multiple scRNA-seq datasets, we demonstrate the superior performance of FBSDE compared to other methods, highlighting its efficacy in accurately inferring developmental trajectories.

Fluorogenic Probes of the Mycobacterial Membrane as Reporters of Antibiotic Action.

The genus Mycobacterium includes species such as Mycobacterium tuberculosis, which can cause deadly human diseases. These bacteria have a protective cell envelope that can be remodeled to facilitate their survival in challenging conditions. Understanding how such conditions affect membrane remodeling can facilitate antibiotic discovery and treatment. To this end, we describe an optimized fluorogenic probe, N-QTF, that reports on mycolyltransferase activity, which is vital for cell division and remodeling. N-QTF is a glycolipid probe that can reveal dynamic changes in the mycobacterial cell envelope in both fast- and slow-growing mycobacterial species. Using this probe to monitor the consequences of antibiotic treatment uncovered distinct cellular phenotypes. Even antibiotics that do not directly inhibit cell envelope biosynthesis cause conspicuous phenotypes. For instance, mycobacteria exposed to the RNA polymerase inhibitor rifampicin release fluorescent extracellular vesicles (EVs). While all mycobacteria release EVs, fluorescent EVs were detected only in the presence of RIF, indicating that exposure to the drug alters EV content. Macrophages exposed to the EVs derived from RIF-treated cells released lower levels of cytokines, suggesting the EVs moderate immune responses. These data suggest that antibiotics can alter EV content to impact immunity. Our ability to see such changes in EV constituents directly results from exploiting these chemical probes.

MMP2hi Fibroblasts Regulate CD8+ T Cell Residency and Inflammation via CD100 in Psoriasis.

BACKGROUND: Psoriasis, a T cell-mediated chronic inflammatory skin condition, is characterized by the interaction of T cells with various cell types, forming an inflammatory microenvironment that sustains psoriatic inflammation. The homeostasis of these tissue-resident T cells are supported by fibroblasts, the primary structural cells in the dermis. In psoriasis, there is an increased expression of matrix metalloproteinase 2 (MMP2), mediating the structural alterations of skin tissues and the modulation of inflammation. Additionally, the CD100-PLXNB2 axis is known to enhance psoriasis inflammation via keratinocytes, and CD103 levels are associated with the severity of psoriasis upon relapse. OBJECTIVE: To elucidate the role of fibroblasts and the MMP2/CD100 axis in modulating psoriasis inflammation. METHODS: CD100 expression and function in psoriasis were assessed using immunofluorescence, ELISA, single-cell transcriptome sequencing, cellular interaction analyses, and qRT-PCR. CD8+ T cells from psoriasis patients were isolated using magnetic beads to investigate the regulatory effect of MMP2 on CD100 expression on their membranes. Single-cell transcriptome sequencing, spatial transcriptome sequencing, mimetic timing analysis, immunofluorescence, and flow cytometry were utilized to determine the origin of MMP2 and its impact on CD103+CD8+ T cells. The hypotheses were further validated in vivo using MMP2 and CD100 inhibitors. RESULTS: Soluble CD100 (sCD100) was significantly upregulated in both psoriatic lesions and peripheral blood, amplifying psoriasis inflammation by promoting the production of inflammatory cytokines by keratinocytes, fibroblasts, and endothelial cells through the sCD100-PLXNB2 axis. Fibroblasts with high MMP2 expression (MMP2hi) exacerbate psoriasis symptoms by facilitating CD100 shedding from CD8+ T cell membranes. Additionally, it was demonstrated that fibroblasts enhance the upregulation of the CD8+ T cell residency factor CD103 in co-cultures with CD8+ T cells. Inhibitors targeting MMP2 and CD100 proved effective in reducing inflammation in a model of imiquimod-induced psoriasis. CONCLUSION: Our findings underscore the pivotal role of MMP2hi fibroblasts in the amplification and recurrence of inflammatory responses in psoriasis. These fibroblasts augment psoriasis inflammation through the CD100-PLXNB2 axis by facilitating CD100 shedding on CD8+ T cell membranes and by upregulating CD103, thereby enhancing CD8+ T cell residency.

Age-related effects on the anterior and posterior hippocampal volumes in 6-21 year olds: A model selection approach.

Although recent studies support significant differences in intrinsic structure, function, and connectivity along the longitudinal axis of the hippocampus, few studies have investigated the normative development of this dimension. In addition, factors known to influence hippocampal structure, such as sex or puberty, have yet to be characterized when assessing age-related effects on its subregions. This study addresses this gap by investigating the relationship of the anterior (antHC) and posterior (postHC) hippocampus volumes with age, and how these are moderated by sex or puberty, in structural magnetic resonance imaging scans from 183 typically developing participants aged 6-21 years. Based on previous literature, we first anticipated that non-linear models would best represent the relationship between age and the antHC and postHC volumes. We found that age-related effects are region-specific, such that the antHC volume remains stable with increasing age, while the postHC shows a cubic function characterized by overall volume increase with age but a slower rate during adolescence. Second, we hypothesized that models, which include biological sex or pubertal status would best describe these relationships. Contrary to expectation, models comprising either biological sex or pubertal status did not significantly improve model performance. Further longitudinal research is needed to evaluate their effects on the antHC and postHC development.

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.

Tuberculosis: hey there, lonely guy!

In this issue of Molecular Cell,Samanovic et al. (2015) identify that the mycobacterial proteasomal substrate encoded by Rv1205, which appears to code for a homolog of the plant-like enzyme LONELY GUY, is responsible for proteasome-mediated nitric oxide resistance.

Cytosporones with Anti-Inflammatory Activities from the Mangrove Endophytic Fungus Phomopsis sp. QYM-13.

Six previously undescribed cytosporone derivatives (phomotones A-E (1-5) and phomotone F (13)), two new spiro-alkanol phombistenes A-B (14-15), and seven known analogs (6-12) were isolated from the mangrove endophytic fungus Phomopsis sp. QYM-13. The structures of these compounds were elucidated using spectroscopic data analysis, electronic circular dichroism (ECD), and 13C NMR calculations. Compound 14 features an unprecedented 1,6-dioxaspiro[4.5]decane ring system. All isolates were evaluated for their inhibitory effect on nitric oxide (NO) in LPS-induced RAW264.7 cells. The results showed that compounds 1, 6, 8, and 11 exhibited potent bioactivities by comparing with positive control. Then, compound 1 displayed the anti-inflammatory effect by inhibiting the MAPK/NF-κB signaling pathways. Molecular docking further revealed the possible mechanism of compound 1 interaction with ERK protein.

Reconstruction strategies for intraoperative CSF leak in endoscopic endonasal skull base surgery: systematic review and meta-analysis.

BACKGROUND: Endoscopic endonasal surgery (EES) is one of the preferred options for skull base pathologies. Cerebrospinal fluid (CSF) leak is a significant complication of EES and neurosurgeons have proposed various reconstructive strategies to decrease this morbidity. We describe and compare the efficacy of these strategies. METHODS: We searched PubMed, Cochrane Library, and Web of Science for publications between 1990 and November 2019. We defined a reconstruction hierarchy of seven levels from inside to outside: fat graft, intracranial intradural layer (inlay), intracranial extradural layer (onlay), buttress, mucosal flap, nasal packing and lumbar drainage. A single-arm analysis was performed for the primary outcome of CSF leak rate. RESULTS: Of 3641 records identified, 48 studies met the inclusion criteria. Pituitary tumors had lower postoperative CSF leak rate than other diseases (1.8% vs. 6.5%, RD = -4.7% [-7.1%, -2.1%]). In high CSF flow group, the post-operative leak rate was reduced by application of mucosal flap (4.3% vs. without mucosal flap at 12.8%, RD = -8.5% [-15.1%, -1.9%]). The use of inlay showed potential of decreasing the post-operative leak rate (5.0% vs. 7.2%, RD = -2.2% [-7.7%, 3.3%]). In low CSF flow group, tampon was better than balloon for nasal packing (1.0% vs. 10.5%, RD = -9.5% [-16.5%, -2.4%]). CONCLUSIONS: Mucosal flap and inlay for high-flow intraoperative CSF leak and tampon (compared with balloon) for low-flow intraoperative CSF leak, improved the postoperative CSF leak rate. Further studies are required to establish more robust evidence.

An Ultra-Precision Absolute-Type Multi-Degree-of-Freedom Grating Encoder.

An absolute-type four-degree-of-freedom (four-DOF) grating encoder that can simultaneously measure the three-axis pose (θx, θy, θz) and one-axis out-of-plane position (Z) of an object with high accuracy is demonstrated for the first time in this research. This grating encoder is composed of a stationary reading head and a movable grating reflector. A light beam from the reading head is projected onto the grating, and three diffracted beams (0th-, +1st-, and -1st-order) are generated, collimated, and received by three separate quadrant photodetectors (QPDs). The information of θx, θy, θz, and Z is coded into spot positions of these three diffracted beams on the QPDs. Thus, the modeling and decoupling algorithms were investigated, and an independent calculation of these four-DOF absolute positions was theoretically guaranteed. A prototype was then designed, constructed, and evaluated. Experimental results verified that the proposed grating encoder could achieve the absolute measurement of four-DOF θx, θy, θz, and Z with an accuracy of sub-arcseconds and sub-micrometers. To the best of our knowledge, the proposed encoder in this research is the first one to achieve absolute simultaneous measurements of four-DOF position and pose with a large measurement range. The success of this new grating encoder can benefit various multi-DOF positioning applications, especially for large-scale synthetic aperture optics (SAO), including stitching off-axis parabolic mirrors and pulse compression grating.

ClpX Is Essential and Activated by Single-Strand DNA Binding Protein in Mycobacteria.

The ClpP1P2 proteolytic complex is essential in Mycobacterium tuberculosis Proteolysis by ClpP1P2 requires an associated ATPase, either ClpX or ClpC1. Here, we sought to define the unique contributions of the ClpX ATPase to mycobacterial growth. We formally demonstrated that ClpX is essential for mycobacterial growth, and to understand its essential functions, we identified ClpX-His-interacting proteins by pulldown and tandem mass spectrometry. We found an unexpected association between ClpX and proteins involved in DNA replication, and we confirm a physical association between ClpX and the essential DNA maintenance protein single-stranded-DNA binding protein (SSB). Purified SSB is not degraded by ClpXP1P2; instead, SSB enhances ATP hydrolysis by ClpX and degradation of the model substrate GFP-SsrA by ClpXP1P2. This activation of ClpX is mediated by the C-terminal tail of SSB, which had been implicated in the activation of other ATPases associated with DNA replication. Consistent with the predicted interactions, depletion of clpX transcript perturbs DNA replication. These data reveal that ClpX participates in DNA replication and identify the first activator of ClpX in mycobacteria.IMPORTANCE Tuberculosis, caused by Mycobacterium tuberculosis, imposes a major global health burden, surpassing HIV and malaria in annual deaths. The ClpP1P2 proteolytic complex and its cofactor ClpX are attractive drug targets, but their precise cellular functions are unclear. This work confirms ClpX's essentiality and describes a novel interaction between ClpX and SSB, a component of the DNA replication machinery. Further, we demonstrate that a loss of ClpX is sufficient to interrupt DNA replication, suggesting that the ClpX-SSB complex may play a role in DNA replication in mycobacteria.

Two-channel six degrees of freedom grating-encoder for precision-positioning of sub-components in synthetic-aperture optics.

We investigate a novel two-channel grating encoder that can perform simultaneous measurements of six-degree-of-freedom (DOF) motions of two adjacent sub-components of synthetic-aperture optics such as pulse-compression gratings(PCGs) and telescope-primary mirrors. The grating encoder consists of a reading head and two separate gratings, which are attached to the back of the sub-components, respectively. The reading head is constructed such that there two identical optical probes can share the same optical components. The two probes are guided to hit each of the two gratings and can detect six-DOF motions simultaneously and independently. For each probe, the incident beam propagates through both a three-axes grating interferometry module and a three-axes diffraction integrated autocollimator-module, which detects translational and rotational movement, respectively. By combining the two modules it is possible to perform six-DOF measurement for a single point. The common-path configuration of the two probes enable identical responses to environmental variation, which ensures high accuracy.

Planar diffractive grating for magneto-optical trap application: fabrication and testing.

The design, fabrication, and demonstration of a planar two-dimensional-crossed reflective diffractive grating are proposed to construct a novel optical configuration, to the best of our knowledge, potentially applied for atom cooling and trapping in a magneto-optical trap. Based on the proposed single-beam single-exposure scheme by means of an orthogonal two-axis Lloyd's mirrors interferometer, we rapidly patterned a ∼1µm period grating capable of providing a uniform intensity of the diffracted beams. The key structural parameters of the grating including the array square hole's width and depth were determined, aiming at providing a high energy of the diffracted beams to perform the atom cooling and trapping. To guarantee the diffracted beams to be overlapped possibly, we adopted a polarized beam splitter to guide the optical path of the incident and zero-order diffracted beams. Therefore, one zero-order diffracted beam with a retroreflected mode and four first-order diffracted beams with appropriate optical path constructed a three-dimensional optical configuration of three orthogonal pairs of counterpropagating beams. Finally, three pairs of the counterpropagating cooling laser beams with 9 mm diameter and >10% diffraction efficiencies were achieved, and the circular polarization chirality, purity, and compensation of the desired diffracted beams are further evaluated, which preliminarily validated a high applicability for the magneto-optical trap system.

Olfactory outcomes after endonasal skull base surgery: a systematic review.

For the last two decades, endonasal approach has been regularly applied to treat skull base lesions. However, postoperative olfactory dysfunction remains an unsolved problem. This systematic review aimed to identify factors that might affect postoperative olfactory prognosis of patients undergoing endonasal surgery for resection of sellar/parasellar lesions. The literature search was conducted comprehensively to exhaust studies which focused on patients' olfaction with objective olfactory assessments after endonasal skull base surgery. We sought to characterize the potential factors that might affect postoperative olfactory outcomes. Nineteen articles met inclusion criteria. We found that (1) endoscopic surgery was beneficial to patients' olfactory prognosis than microscopic surgery (incidence of postoperative decreased olfactory function: 18.48% (39/211) for the endoscopic group and 36.88% (52/141) for the microscopic group, P < 0.01); meta-analysis for single rate, 20% (95% CI 9-30%) for the endoscopic group and 35% (95% CI 0-72%) for the microscopic group); (2) harvesting septal flaps was an unfavorable factor for olfactory recovery and the rescue flap technique should be preferred compared with the HB flap; (3) no evidence showed that resection of the middle turbinate was detrimental to recovery of olfaction. Patients undergoing endoscopic endonasal surgery may have better olfactory outcomes than those undergoing microscopic endonasal surgery for resection of sellar/parasellar lesions. Special attention should be paid when using septal flaps is planned and the rescue flap technique should be the preferred choice. After resecting the middle turbinate, patients' olfaction still has a great chance of returning to the baseline. More homogeneous and high-quality studies are needed for further assessment.

Optimal combination of temperature and photoperiod for sex steroid hormone secretion and egg development of Oreochromis niloticus as determined by response surface methodology.

For successful reproduction of farmed fish, it is important to understand the relationship between gonadal development and environmental factors such as temperature and photoperiod. In this study, we determined the effects of temperature (T) and photoperiod (Pp) on serum estradiol-17ß (E2) and progesterone (P) contents, gonadosomatic index (GSI), and oocyte development in female tilapia. We used a central composite experimental design and response surface methodology. The experimental ranges were 18-36 °C for T and 0-24 h for Pp. The results show that the quadratic effects of T and Pp were highly significant for serum E2 and P contents, GSI, and the ratio of stage III to stage II oocytes (P < 0.01), and that the linear effects of T and Pp were also significant for these indicators (P < 0.05). The T × Pp interaction significantly affected serum E2 content (P < 0.05). Serum E2 and P content, GSI, and the ratio of stage III to stage II oocytes increased and then decreased with increasing T or Pp. The best combination of T and Pp for egg development was 28.6 °C/14.29 h. We observed the part of ovarian tissue containing stage V oocytes that are about to be discharged. Shortening the photoperiod or lowering the water temperature delayed the development of ovarian tissue so that most oocytes remained at stage II, and there were many atretic follicles. There were significant positive correlations between female GSI and serum E2, P, and the ratio of stage III to stage II oocytes. The results of this study provide a reference for the regulation of temperature and photoperiod to control broodstock gonadal maturation and hormone-induced broodstock spawning.

Design and validation of a 3D-printed simulator for endoscopic third ventriculostomy.

BACKGROUND: Simulation-based training has been considered as the most promising curriculum for neurosurgical education to finally improve surgical skills with the greatest efficiency and safety. However, most of the simulators including physical models and virtual reality systems are relatively expensive, which limits their promotion. In this study, the authors tried to develop a realistic, low-cost, and reusable simulator for endoscopic third ventriculostomy (ETV) and evaluate its validity. METHODS: A 3D-printed rigid skull with the ventricular system originated from a de-identified patient with obstructive hydrocephalus was constructed. The third ventricular floor was designed as a replaceable module. Thirty-nine neurosurgeons tested the simulator and a rating system was established to assess their performance. All participants filled out questionnaires to evaluate the simulator after training. Five neurosurgical students were recruited to finish the whole training for ten times in order to explore the learning curve of ETV. RESULTS: We found that (1) the more experienced surgeons performed obviously better than the rather inexperienced surgeons which verified that our model could reflect the ability of the trainees; (2) as the training progressed, the scores of the post-graduates increased and the fifth training average score was obviously higher than their first training average score. The feedback questionnaires showed the average scores for value of the simulator as a training tool and global rating were 3.15 and 3.54 (on a 4-point scale). CONCLUSION: Our model was practical for ETV training. The results of our program showed that our model could precisely reflect the operators' ability to perform ETV and could make it more efficient to master basic skills.

Dietary vitamin E deficiency inhibits fat metabolism, antioxidant capacity, and immune regulation of inflammatory response in genetically improved farmed tilapia (GIFT, Oreochromis niloticus) fingerlings following Streptococcus iniae infection.

Vitamin E plays an important role in maintaining normal metabolism and physiological functions in animals. The health of fish fingerlings directly affects the rate of disease incidence in adult fish, and healthy fingerlings ultimately result in better breeding outcomes for cultured fish. To date, no previous studies have focused on the effects vitamin E deficiency on tilapia at the fingerling stage. In this study, we investigated the effects of dietary vitamin E on the growth, fat metabolism, antioxidant capacity, and inflammatory response of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) fingerlings. Vitamin E at different concentrations (0, 20, 40, 80, 160, and 320 mg/kg) was added to the diet and GIFT were fed for 55 days. Then, the GIFT were intraperitoneally injected with Streptococcus iniae and tested for infection. Vitamin E deficiency decreased growth and increased the food conversion ratio of GIFT fingerlings. Vitamin E deficiency also reduced the white blood cell count, increased hematocrit and hemoglobin contents in the blood, increased serum aspartate aminotransferase and alanine aminotransferase activities, and increased liver stress (P < 0.05). Vitamin E deficiency inhibited fat metabolism, down-regulated the expression of genes encoding lipoprotein lipase and heart-type and liver-type fatty acid-binding proteins, and increased serum total protein and fat deposition. Vitamin E deficiency significantly decreased superoxide dismutase, glutathione peroxidase, and catalase activities, increased malondialdehyde content, and caused oxidative damage. Vitamin E deficiency also up-regulated the expression of genes encoding interleukin 1ß and tumor necrosis factor α in the head kidney, and stimulated a pro-inflammatory response. Overall, vitamin E deficiency inhibited growth, impaired fat metabolism, and disrupted the inflammatory response of GIFT fingerlings, whereas vitamin E supplementation in the diet reversed these negative effects. The diets with high concentrations of vitamin E (160-320 mg/kg) led to vitamin E accumulation in the fish tissues and rapid activation of the inflammatory response and antioxidant capacity in GIFT fingerlings exposed to S. iniae.

Protein mistranslation: friend or foe?

The translation of genes into functional proteins involves error. Mistranslation is a known cause of disease, but, surprisingly, recent studies suggest that certain organisms from all domains of life have evolved diverse pathways that increase their tolerance of translational error. Although the reason for these high error rates are not yet clear, evidence suggests that increased mistranslation may have a role in the generation of diversity within the proteome and other adaptive functions. Error rates are regulated, and there appears to be an optimal mistranslation rate that varies by organism and environmental condition. Advances in unbiased interrogation of error types and experiments involving wild organisms may help our understanding of the potentially adaptive roles for protein translation errors.

The Coexistence of Growth Hormone-Producing Pituitary Adenoma and Rathke Cleft Cyst: How Can We Diagnosis Preoperation?

Pituitary adenoma (PA) rarely coexists with Rathke's cleft cyst (RCC). Previously, only 13 cases of patients with growth hormone (GH)-producing PA and concomitant RCC have been reported. Here, the authors report a 54-year-old female patient with a GH-secreting PA coexisting with an RCC. Acromegaly was diagnosed according to the physical examination and endocrine data. Preoperatively, the coronal magnetic resonance imaging (MRI) contained 2 different signal intensities, these unusually MRI findings for the intrasellar mass were rarely. According to our clinical experience for diagnosis of PA and RCC, besides GH-producing PA in this case, but the possibility of concomitant RCC should be considered. One-and-a-half nostril endoscopic transsphenoidal approach was performed. Intraoperatively, the adenoma was successfully removed and a large amount of grayish fluid from the cyst was released. The endocrine testing was normal soon after the operation and the patient remained well for a follow-up period of 3 months. The postoperative MRI (obtained 3 months after surgery) showed no intrasellar and suprasellar mass. The authors retrospectively analyzed the all 14 cases of concomitant GH-secreting PAs and RCCs and summarized MRI characteristics. When preoperative MRI contained 2 different signal intensities, one mass lesion showed low or isointense signal on the T1-weighted and T2-weighted images, whereas the other lesion showed low signal on the T1-weighted images and hyperintense on the T2-weighted images, the collision MRI features may be helpful for the preoperative diagnosis of concomitant PAs and RCCs.

Trichophyton rubrum Infection Characterized by Majocchi's Granuloma and Deeper Dermatophytosis: Case Report and Review of Published Literature.

Infections caused by Trichophyton rubrum are very common in dermatological disease. It most often appears as superficial cutaneous mycosis, such as tinea manuum, tinea pedis, and tinea corporis. However, deep infection caused by T. rubrum was rarely reported. We describe a case of mixed type of deep infection caused by T. rubrum in a 45-year-old man with no significant immunodeficiency. This patient had a history of onychomycosis on the toenails without regular treatment for nearly 6 years. And, he had erythema, papule, and nodules on the submandibular area, neck, and chest for almost 1 year. After treated with intravenous infusion of cefotiam for 2 weeks, the lesion aggravated. The fungal direct microscopic examination of pyogenic fluid was positive, and the fungal cultures that produced reddish-brown and yellow pigment showed cottony, wooly, and white colony. After the DNA sequencing, it was identified as T. rubrum. We gave the patient oral terbinafine 250 mg per day and bifonazole cream for external use. Six months later, the patient's skin lesion was disappeared, and healthy nail growth was seen in two-thirds of nail bed. The terbinafine is effective against deep infection caused by T. rubrum.