Myxovirus resistance protein A (MxA) expression in myositides: Sarcoplasmic expression is common in both dermatomyositis and lupus myositis.

INTRODUCTION/AIMS: Myxovirus resistance protein A (MxA) is a type I interferon (IFN1) pathway activation marker and MxA sarcoplasmic expression is currently recognized as a highly specific marker for dermatomyositis (DM). However, we have frequently observed endothelial tubuloreticular inclusions (TRI), another surrogate IFN1 activation marker, in a variety of overlap myositides. The aim of this study was to examine MxA expression in those myositides. METHODS: We retrospectively performed MxA immunostaining on a wide range of myositides. RESULTS: MxA sarcoplasmic expression was present in DM (94.4%, 17/18), active lupus myositis (LM, 80%,16/20), inactive LM (36%, 4/11), antisynthetase syndrome (ASyS, 20%, 2/10), systemic sclerosis (13%, 2/15), Sjogren's syndrome (7.7%, 1/13), and human immunodeficiency virus (HIV) myositis (5.6%, 1/18) and was absent in immune-mediated necrotizing myopathy (IMNM, 0/16) and hydroxychloroquine myopathy (0/5). The sensitivity and specificity of MxA sarcoplasmic expression for LM and DM combined compared with all other myositides were 84.6% (95% CI: 69.5-94.1) and 92.1 (95% CI: 83.6-97.0), respectively, and superior to TRIs. MxA capillary expression was nonspecific. Histologically, 35% of LM cases demonstrated a unique panfascicular necrotizing myopathy pattern. The remainder of the LM cases had significant morphological overlap with DM/ASyS (20%), IMNM (20%), or polymyositis (15%). DISCUSSION: MxA sarcoplasmic expression is highly prevalent in LM and DM and is a useful marker in differentiating DM and LM from other myositides. LM can manifest in various pathology patterns that need to be differentiated from DM, IMNM, ASyS, and polymyositis.

Investigation the mechanism of iron overload-induced colonic inflammation following ferric citrate exposure.

Iron overload occurs due to excessive iron intake compared to the body's demand, leading to iron deposition and impairment of multiple organ functions. Our previous study demonstrated that chronic oral administration of ferric citrate (FC) caused colonic inflammatory injury. However, the precise mechanism underlying this inflammatory response remains unclear. The current study aims to investigate the mechanism by which iron overload induced by FC exposure leads to colonic inflammation. To accomplish this, mice were orally exposed to three different concentrations of FC (71 mg/kg/bw (L), 143 mg/kg/bw (M) and 286 mg/kg/bw (H)) for continuous 16 weeks, with the control group receiving ultrapure water (C). Exposure to FC caused disturbances in the excretory system, altered colonic flora alpha diversity, and enriched pathogenic bacteria, such as Mucispirillum, Helicobacter, Desulfovibrio, and Shigella. These changes led to structural disorders of the colonic flora and an inflammatory response phenotype characterized by inflammatory cells infiltration, atrophy of intestinal glands, and irregular thickening of the intestinal wall. Mechanistic studies revealed that FC-exposure activated the NF-κB signaling pathway by up-regulating TLR4, MyD88, and NF-κB mRNA levels and protein expression. This activation resulted in increased production of pro-inflammatory cytokines, further contributing to the colonic inflammation. Additionally, in vitro experiments in SW480 cells confirmed the activation of NF-κB signaling pathway by FC exposure, consistent with the in vivo findings. The significance of this study lies in its elucidation of the mechanism by which iron overload caused by FC exposure leads to colonic inflammation. By identifying the role of pathogenic bacteria and the NF-κB signaling pathway, this study could potentially offer a crucial theoretical foundation for the research on iron overload, as well as provide valuable insights for clinical iron supplementation.

Ectopic PLAG1 induces muscular dystrophy in the mouse.

Even though various genetic mutations have been identified in muscular dystrophies (MD), there is still a need to understand the biology of MD in the absence of known mutations. Here we reported a new mouse model of MD driven by ectopic expression of PLAG1. This gene encodes a developmentally regulated transcription factor known to be expressed in developing skeletal muscle, and implicated as an oncogene in certain cancers including rhabdomyosarcoma (RMS), an aggressive soft tissue sarcoma composed of myoblast-like cells. By breeding loxP-STOP-loxP-PLAG1 (LSL-PLAG1) mice into the MCK-Cre line, we achieved ectopic PLAG1 expression in cardiac and skeletal muscle. The Cre/PLAG1 mice died before 6 weeks of age with evidence of cardiomyopathy significantly limiting left ventricle fractional shortening. Histology of skeletal muscle revealed dystrophic features, including myofiber necrosis, fiber size variation, frequent centralized nuclei, fatty infiltration, and fibrosis, all of which mimic human MD pathology. QRT-PCR and Western blot revealed modestly decreased Dmd mRNA and dystrophin protein in the dystrophic muscle, and immunofluorescence staining showed decreased dystrophin along the cell membrane. Repression of Dmd by ectopic PLAG1 was confirmed in dystrophic skeletal muscle and various cell culture models. In vitro studies showed that excess IGF2 expression, a transcriptional target of PLAG1, phenocopied PLAG1-mediated down-regulation of dystrophin. In summary, we developed a new mouse model of a lethal MD due to ectopic expression of PLAG1 in heart and skeletal muscle. Our data support the potential contribution of excess IGF2 in this model. Further studying these mice may provide new insights into the pathogenesis of MD and perhaps lead to new treatment strategies.

TRIM67 Implicates in Regulating the Homeostasis and Synaptic Development of Mitral Cells in the Olfactory Bulb.

In recent years, olfactory dysfunction has attracted increasingly more attention as a hallmark symptom of neurodegenerative diseases (ND). Deeply understanding the molecular basis underlying the development of the olfactory bulb (OB) will provide important insights for ND studies and treatments. Now, with a genetic knockout mouse model, we show that TRIM67, a new member of the tripartite motif (TRIM) protein family, plays an important role in regulating the proliferation and development of mitral cells in the OB. TRIM67 is abundantly expressed in the mitral cell layer of the OB. The genetic deletion of TRIM67 in mice leads to excessive proliferation of mitral cells in the OB and defects in its synaptic development, resulting in reduced olfactory function in mice. Finally, we show that TRIM67 may achieve its effect on mitral cells by regulating the Semaphorin 7A/Plexin C1 (Sema7A/PlxnC1) signaling pathway.

Optimization of culture medium and scale-up production of astaxanthin using corn steep liquor as substrate by response surface methodology.

Astaxanthin is a natural carotenoid with strong antioxidant activity. In this paper, the effects of carbon source, corn steep liquor, distiller grains, and initial pH on the growth and astaxanthin production of Phaffia rhodozyma D3 were evaluated. The optimal medium composition was 32 g/L glucose, 12 g/L corn steep liquor as nitrogen source, and the initial pH was 6.7. Phaffia rhodozyma D3 was cultured in a shake flask under these optimized conditions, the biomass was 6.47 g/L, the astaxanthin/OD475 was 15.16, and the astaxanthin content was 1.41 mg/g. The astaxanthin content was further increased to 4.70 mg/g by the combination of TiO2 stimulation and the expanding cultivation of P. rhodozyma D3 in a 5 L fermenter, which was 2.81 times that of the control group. Expanding fermentation implies the possibility of large-scale production in the astaxanthin industry. Corn steep liquor was used as an alternative nitrogen source to culture P. rhodozyma D3, which could both reduce the production cost of astaxanthin and increased the by-products utilization rate.

Metabolite analysis of soybean oil on promoting astaxanthin production of Phaffia rhodozyma.

BACKGROUND: Astaxanthin is a carotenoid with strong antioxidant property. In addition, it has anti-cancer, anti-tumor, anti-inflammatory and many other functions. The micro-organisms that mainly produce astaxanthin are Haematococcus pluvialis and Phaffia rhodozyma. Compared with H. pluvialis, P. rhodozyma has shorter fermentation cycle and easier to control culture conditions, but the yield of astaxanthin in P. rhodozyma is low. This article studied how to improve the astaxanthin production of P. rhodozyma. RESULTS: The results showed that when 10 mL L-1 soybean oil was added to the culture medium, astaxanthin production increased significantly, reaching 7.35 mg L-1 , which was 1.4 times that of the control group, and lycopene and ß-carotene contents also increased significantly. Through targeted metabolite analysis, the fatty acids in P. rhodozyma significantly increased under the soybean oil stimulation, especially the fatty acids closely related to the formation of astaxanthin esters, included palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1n9), linoleic acid (C18:2n6), α-linolenic acid (C18:3n3) and γ-linolenic acid (C18:3n6), thereby increasing the astaxanthin esters content. CONCLUSION: It showed that the addition of soybean oil can promote the accumulation of astaxanthin by promoting the increase of astaxanthin ester content. © 2022 Society of Chemical Industry.

The efficacy of immunohistochemistry in the diagnosis of molecular genetic alterations in central nervous system gliomas: Next-generation sequencing of 212 mutations in 112 patients.

Identification of molecular genetic alterations has become an important part of diagnosis and care of patients with brain tumors. Comparisons of immunohistochemistry (IHC) with DNA sequencing techniques have suggested that IHC is useful for identifying surrogates of mutations in gliomas; however, studies of the efficacy are relatively few. Our aim was to compare IHC in our neuropathology laboratory with a commercially available next-generation sequencing (NGS) platform, Tempus xT. We studied 212 immunohistochemically stained sections of gliomas to identify mutations of isocitrate dehydrogenase (IDH), p53, BRAF, the α-thalassemia/mental retardation syndrome X-linked protein (ATRX), and histone H3. Tempus xT NGS confirmed the IHC diagnosis of IDH1/R132H in 102 of 102 patients (100%), BRAF/V600E in 14 of 14 (100%) patients and H3/K27M in 10 of 10 (100%) patients. For p53, NGS confirmed the IHC diagnosis of mutation in 47 of 53 (87%) patients. For 6 patients, IHC was interpreted as wild-type while NGS indicated a mutation. NGS confirmed the IHC diagnosis of ATRX mutation in 29 of 31 (94%) patients. In 1 patient, IHC predicted a mutation that was not confirmed by NGS, and in another, IHC predicted wild-type, but NGS showed mutant. In 2 other patients, IHC diagnosis of ATRX mutation was equivocal; 1 was mutant and 1 was wild-type by NGS. Our single-center study suggests that IHC for IDH1/R132H, BRAF/V600E, and H3/K27M is highly reliable and may be used confidently in clinical practice. IHC for p53 and ATRX mutations is often reliable but possibly problematic, and genetic studies may be necessary to determine astrocytic or oligodendroglial differentiation.

SWI/SNF deficient central nervous system neoplasms.

The SWItch/Sucrose Non-Fermentable (SWI/SNF) complexes are ubiquitous ATP dependent chromatin remodeling complexes that provide epigenetic regulation of gene expressions across the genome. Different combination of SWI/SNF subunits allow tissue specific regulation of critical cellular processes. The identification of SMARCB1 inactivation in pediatric malignant rhabdoid tumors provided the first example that the SWI/SNF complex may act as a tumor suppressor. It is now estimated at least 20% of all human tumors contain mutations in the subunits of the SWI/SNF complex. This review summarizes the central nervous system tumors with alterations in the SWI/SNF complex genes. Atypical teratoid/rabdoid tumor (AT/RT) is a highly aggressive embryonal tumor genetically characterized by bi-allelic inactivation of SMARCB1, and immunohistochemically shows complete absence of nuclear expression of its protein product INI1. A small subset of AT/RT show retained INI1 expression but defects in another SWI/SNF complex gene SMARCA4. Embryonal tumors with medulloblastoma, pineoblastoma, or primitive neuroectodermal morphology but loss of INI1 expression are now classified as AT/RT. Cribriform neuroepithelial tumor (CRINET) is an intra or para-ventricular tumor that has similar SMARCB1 alterations as AT/RT but generally has a benign clinical course. Besides AT/RT and CRINET, compete loss of nuclear INI1 expression has also been reported in poorly differentiated chordoma and intracranial myxoid sarcoma within the central nervous system. Families with non-truncating SMARCB1 mutations are prone to develop schwannomatosis and a range of developmental syndromes. The schwannomas in these patients usually demonstrate a mosaic INI1 staining pattern suggestive of partial residual protein function. Finally, clear cell meningioma is a WHO grade II variant meningioma characterized by bi-allelic inactivation of the SMARCE1 gene and immunohistochemically show loss of its protein product BAF57 expression in tumor cell nuclei.

Biallelic loss of function variants in SYT2 cause a treatable congenital onset presynaptic myasthenic syndrome.

Synaptotagmins are integral synaptic vesicle membrane proteins that function as calcium sensors and regulate neurotransmitter release at the presynaptic nerve terminal. Synaptotagmin-2 (SYT2), is the major isoform expressed at the neuromuscular junction. Recently, dominant missense variants in SYT2 have been reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated. Here we report seven patients of five families, with biallelic loss of function variants in SYT2, clinically manifesting with a remarkably consistent phenotype of severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings were consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in three patients showed clinical improvement with increased strength and function. This series further establishes SYT2 as a CMS-disease gene and expands its clinical and genetic spectrum to include recessive loss-of-function variants, manifesting as a severe congenital onset presynaptic CMS with potential treatment implications.

A pattern-based approach to the interpretation of skeletal muscle biopsies.

The interpretation of muscle biopsies is complex and provides the most useful information when integrated with the clinical presentation of the patient. These biopsies are performed for workup of a wide range of diseases including dystrophies, metabolic diseases, and inflammatory processes. Recent insights have led to changes in the classification of inflammatory myopathies and have changed the role that muscle biopsies have in the workup of inherited diseases. These changes will be reviewed. This review follows a morphology-driven approach by discussing diseases of skeletal muscle based on a few basic patterns that include cases with (1) active myopathic damage and inflammation, (2) active myopathic damage without associated inflammation, (3) chronic myopathic changes, (4) myopathies with distinctive inclusions or vacuoles, (5) biopsies mainly showing atrophic changes, and (6) biopsies that appear normal on routine preparations. Each of these categories goes along with certain diagnostic considerations and pitfalls. Individual biopsy features are only rarely pathognomonic. Establishing a firm diagnosis therefore typically requires integration of all of the biopsy findings and relevant clinical information. With this approach, a muscle biopsy can often provide helpful information in the diagnostic workup of patients presenting with neuromuscular problems.

Role of Nerve and Muscle Biopsies in Pediatric Patients in the Era of Genetic Testing.

BACKGROUND: An operative biopsy is an important component in the diagnosis and treatment of neuromuscular disorders (NMDs). However, recent advances in molecular genetics suggest less invasive genetic testing should be the initial approach. The purpose of our study was to demonstrate the diagnostic value of muscle or nerve biopsy within the pediatric population at a pediatric academic center and offer recommendations for genetic testing in relation to biopsy to achieve the highest diagnostic yield. METHODS: Following institutional review board approval, we retrospectively reviewed the electronic medical record of 221 pediatric patients who underwent muscle and/or nerve biopsy for suspicion of NMD from January 2007 to March 2018. Demographics, family history, clinical presentations, genetic testing results, pathology results, anesthesia complications, clinical diagnoses, and clinic follow-up data were collected. Chi-square analysis was done for statistical significance. RESULTS: A total of 220 underwent muscle biopsy, and 15 underwent nerve biopsy. Not all patients received genetic testing. The average age at biopsy was 7.7 y. Biopsy revealed significant histologic abnormalities in 62.9% (139), directly leading to a specific clinical diagnosis in 33.9% (75). When genetic testing was done before biopsy, definite pathogenic variants were found in 7.6% (9). When genetic testing was done after biopsy, definite pathogenic variants were found in 45.0% (27). Genetic testing yield for pathogenic variants was higher when done after biopsy (P value < 0.00001). CONCLUSIONS: Muscle and nerve biopsies may provide significant diagnostic value. Biopsy helped to rule in or out NMD and guide genetic testing. Our data suggest NMD genetic testing yield was higher when done after biopsy.

Rapid progression to glioblastoma in a subset of IDH-mutated astrocytomas: a genome-wide analysis.

According to the recently updated World Health Organization (WHO) classification (2016), grade II-III astrocytomas are divided into IDH-wildtype and IDH-mutant groups, the latter being significantly less aggressive in terms of both progression-free and total survival. We identified a small cohort of WHO grade II-III astrocytomas that harbored the IDH1 R132H mutation, as confirmed by both immunohistochemistry and molecular sequence analysis, which nonetheless had unexpectedly rapid recurrence and subsequent progression to glioblastoma. Among these four cases, the mean time to recurrence as glioblastoma was only 16 months and the mean total survival among the three patients who have died during the follow-up was only 31 months. We hypothesized that these tumors had other, unfavorable genetic or epigenetic alterations that negated the favorable effect of the IDH mutation. We applied genome-wide profiling with a methylation array (Illumina Infinium Human Methylation 450k) to screen for genetic and epigenetic alterations in these tumors. As expected, the methylation profiles of all four tumors were found to match most closely with IDH-mutant astrocytomas. Compared with a control group of four indolent, age-similar WHO grade II-III astrocytomas, the tumors showed markedly increased levels of overall copy number changes, but no consistent specific genetic alterations were seen across all of the tumors. While most IDH-mutant WHO grade II-III astrocytomas are relatively indolent, a subset may rapidly recur and progress to glioblastoma. The precise underlying cause of the increased aggressiveness in these gliomas remains unknown, although it may be associated with increased genomic instability.

Unusual skull tumors with psammomatoid bodies: a diagnostic challenge.

AIM: We describe a series of three diagnostically challenging, histologically similar fibro-osseous skull masses. METHODS: The cases were identified in our archives among 50,000 neuropathology specimens. A comprehensive review of the histological, immunohistochemical, ultrastructural, and imaging features as well as the clinical outcome was performed. RESULTS: The routine histology was similar in all 3 cases and showed spindle cell proliferations with frequent calcospheres or psammomatoid bodies. There was no evidence of an underlying subdural component. Immunohistochemistry for the meningioma markers EMA and SSTR2A raised the possibility of intraosseous meningioma, as all 3 lesions were convincingly positive for epithelial membrane antigen (EMA) and 1 lesion was convincingly positive for the somatostatin receptor subtype 2A (SSTR2A); weak, questionable positivity for SSTR2 was present in the remaining 2 cases. In addition, electron microscopy was available in 1 case and showed features consistent with meningioma. CONCLUSIONS: Overall, the findings were most consistent with intraosseous meningioma. Primary intraosseous meningiomas are rare lesions that may present a diagnostic challenge. It is important to consider meningiomas in the differential diagnosis, as extradural meningiomas are associated with an increased risk of recurrence and may occasionally undergo malignant transformation.
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Posterior fossa tumor with distinct choroid plexus papilloma and ependymoma components.

Synchronous occurrence of multiple primary central nervous system (CNS) tumors of different histological types is uncommon in patients without radiation history or genetic syndrome association. We herein report a sporadic case of posterior fossa tumor with synchronous choroid plexus papilloma (CPP) and ependymoma (EP) components. A 7-year-old girl with no significant past or familial medical history presented with 2 years of migraine type headaches. Brain magnetic resonance imaging showed a cystic mass with a mural enhancing nodule centered within the cerebellar vermis. The patient underwent gross total resection of the tumor. Histologic examination showed a tumor with two distinct components. The predominant component demonstrated classic morphological and immunohistochemical characteristics of choroid plexus papilloma CPP, WHO grade I. However, there were a few discrete foci, where tumor cells showed architectural, cytological, and immunohistochemical features characteristic of an ependymoma, WHO grade II. In addition, there was exuberant piloid gliosis secondary to infiltration of the CPP component into the adjacent brain parenchyma. Followup brain imaging at 14 months after surgery showed no evidence of residual or recurrent tumor. To the best of our knowledge, this is the first reported case of synchronous CPP and EP in the posterior fossa.

Extraneural metastatic ependymoma: distant metastasis to the pleura, lungs, lymph nodes and bone.

Ependymomas are neuroepithelial tumours arising from ependymal cells surrounding the cerebral ventricles that rarely metastasise to extraneural structures. This spread has been reported to occur to the lungs, lymph nodes, liver and bone. We describe the case of a patient with recurrent CNS WHO grade 3 ependymoma with extraneural metastatic disease. He was treated with multiple surgical resections, radiation therapy and salvage chemotherapy for his extraneural metastasis to the lungs, bone, pleural space and lymph nodes.

Energy metabolism analysis of exogenous glutamate on promoting co-accumulation of astaxanthin yield and biomass in Phaffia rhodozyma D3.

Effective metabolic regulators play an essential role in regulating astaxanthin biosynthesis in Phaffia rhodozyma. In this study, it was found that 5 mM glutamate increased the astaxanthin yield and biomass of P. rhodozyma D3 to 22.34 mg/L and 6.12 g/L, which were 1.22 and 1.33 times higher than the control group, respectively. Meanwhile, glucose uptake was increased and the level of reactive oxygen species (ROS) was reduced with 5 mM glutamate. To further explore the interrelationship between glutamate and astaxanthin synthesis, the energy metabolism of P. rhodozyma D3 with and without glutamate was analysed. Glutamate promoted the Embden-Meyerhof-Parnas pathway (EMP) metabolic flux, modulated the tricarboxylic acid (TCA) cycle and the pentose phosphate pathway (PPP), activated the ornithine cycle and purine metabolism, and provided more ATP and NADPH for astaxanthin accumulation. This study clarified the possible mechanism by which glutamate promoted astaxanthin accumulation in P. rhodozyma.

What's new in neuromuscular pathology 2022: myopathy updates and gene therapies.

This compilation of new changes in the diagnosis and treatment of muscle and nerve disease is extracted from the latest publications from the European Neuromuscular Centre International workshops, FDA.gov and clinicaltrials.gov.

Polaron states of the full-configuration defects in metal halide perovskites.

The systematical analysis for varieties of defects with different depths and lattice relaxation strengths in metal halide perovskites (MHPs) is a challenging task. Here, we study the energy shifts of the full-configuration defects due to the polaron effect based on the all-coupling variational method in MHPs, where these polaron states are formed stemming from different defect species coupling with the longitudinal optical phonon modes via Fro¨hlich mechanism. We find that the polaron effect results in defect levels varying from tens to several hundreds of meV, which are very close to the correction of defect levels due to the defect-polaron effect, especially for these defects migration proved in the recent experiments in MHPs. These results provide the significant enlightenment not only for analyzing the radiation and non-radiation processes of carriers mediated by defects, but also for optimizing defect effect in the photovoltaic and photoelectric devices based on MHPs materials.

Net39 protects muscle nuclei from mechanical stress during the pathogenesis of Emery-Dreifuss muscular dystrophy.

Mutations in genes encoding nuclear envelope proteins lead to diseases known as nuclear envelopathies, characterized by skeletal muscle and heart abnormalities, such as Emery-Dreifuss muscular dystrophy (EDMD). The tissue-specific role of the nuclear envelope in the etiology of these diseases has not been extensively explored. We previously showed that global deletion of the muscle-specific nuclear envelope protein NET39 in mice leads to neonatal lethality due to skeletal muscle dysfunction. To study the potential role of the Net39 gene in adulthood, we generated a muscle-specific conditional knockout (cKO) of Net39 in mice. cKO mice recapitulated key skeletal muscle features of EDMD, including muscle wasting, impaired muscle contractility, abnormal myonuclear morphology, and DNA damage. The loss of Net39 rendered myoblasts hypersensitive to mechanical stretch, resulting in stretch-induced DNA damage. Net39 was downregulated in a mouse model of congenital myopathy, and restoration of Net39 expression through AAV gene delivery extended life span and ameliorated muscle abnormalities. These findings establish NET39 as a direct contributor to the pathogenesis of EDMD that acts by protecting against mechanical stress and DNA damage.

Titanium dioxide-mediated fatty acids promoted carotenoid synthesis in Phaffia rhodozyma PR106 analyzed whole genome.

Carotenoid, as good colorant and antioxidant, is widely used in the fields of food, medicine and feed. The whole genome of P. rhodozyma PR106 strain with 228.77 mg/L carotenoid (mainly included astaxanthin, ß-carotene and lycopene) yield was sequenced, and the genome size was 16.18 Mb, the GC content was 47%. The genetic evolution analysis indicated that PR106 greatly changed in evolution process, and closely related to P. rhodozyma CBS7918. Under 500 mg/L titanium dioxide (TiO2) stress, carotenoid yield of PR106 was 2.15 times that of the control for 48 h, and was 305.12 mg/L in PR106 to 72 h, interestingly, the yield of oleate, linoleate and α-linolenate also increased significantly among 51 fatty acids by targeted metabolomics analysis. TiO2 promoted carotenoid synthesis of PR106 by forming astaxanthin esters to reduce the feedback inhibition of carotenoid synthesis. These results provided a theoretical basis for carotenoid production and development using P. rhodozyma.