The expression and clinical significance of UHRF1 in soft tissue sarcomas and its prognostic value.

To explore the expression and prognostic value of UHRF1 gene in soft tissue sarcoma (STS) and its related molecular mechanism. The expression data and clinicopathological parameters of STS were downloaded from the Cancer Genome Atlas (TCGA). The expression level of UHRF1 in STS and adjacent tissues and its relationship with clinicopathological characteristics were analyzed. The expression level of UHRF1 in STS tissues was significantly higher than that in paracancerous tissues (P < .001), and the overall survival (OS) time of patients with high UHRF1 expression was significantly shorter than that of patients with low UHRF1 expression (P = .002). The expression of UHRF1 was correlated with tumor necrosis, histological type and metastasis, and the differences were statistically significant (P = .013; P = .001; P = .002). The area ratio under receiver operating characteristic (ROC) curve between STS tissue and adjacent tissue of UHRF1 expression was 0.994. Number of tumors (HR = 0.416, 95%CI = 0.260-0.666, P < .001), depth of tumor (HR = 2.888, 95%CI = 0.910-9.168, P = .033), metastasis (HR = 2.888, 95% CI = 1.762-4.732, P < .001), residual tumor (HR = 2.637, 95% CI = 1.721-4.038, P < .001) and UHRF1 expression (HR = 1.342, 95% CI = 1.105-1.630, P = .003) were significantly associated with OS, and high expression of UHRF1 (HR = 1.387, 95%CI = 1.008-1.907, P = .044) was an independent risk factor for the prognosis of STS patients. The results of the nomogram exhibited that UHRF1 expression level had a significant effect on the total score value. GSEA enrichment analysis suggested that UHRF1 was involved in 14 signaling pathways regulating mRNA spliceosome, cell cycle, P53 signaling pathway were identified. Single sample gene set enrichment analysis (ssGSEA) exhibited that the expression of UHRF1 in STS was positively correlated with the level of Th2 cell infiltration, and negatively correlated with plasmacytoid dendritic cells (pDC), natural killer cells (NK), Eosinophils, Mast cells, etc. UHRF1 expression is involved in the immune microenvironment of HCC and affects the occurrence and development of HCC. UHRF1 is highly expressed in STS tissues. It is involved in the regulation of multiple tumor-related signaling pathways and immune cell microenvironment, suggesting that UHRF1 may be a potential molecular marker for prognosis prediction and targeted therapy of STS patients.

Modulation of copper sites in porphyrin metal-organic frameworks for electrochemical ascorbic acid sensing.

Two metal-organic frameworks (MOFs) with different Cu-centered coordination structures were synthesized. By introducing 4,4-bipyridine as a linker in the Cu-MOFs, we have discovered that Cu-O, instead of Cu-N, is the active site with higher electrocatalytical activity towards ascorbic acid, which is essential to understand and develop Cu-based ascorbic acid sensors.

Fabrication and Evaluation of Hyaluronidase-Responsive Scaffolds by Electrospinning with Antibacterial Properties for Tympanic Membrane Repair.

Tympanic membrane perforation (TMP) is prevalent in clinical settings. Patients with TMPs often suffer from infections caused by Staphylococcus aureus and Pseudomonas aeruginosa, leading to middle ear and external ear canal infections, which hinder eardrum healing. The objective of this study is to fabricate an enzyme-responsive antibacterial electrospun scaffold using poly(lactic-co-glycolic acid) and hyaluronic acid for the treatment of infected TMPs. The properties of the scaffold were characterized, including morphology, wettability, mechanical properties, degradation properties, antimicrobial properties, and biocompatibility. The results indicated that the fabricated scaffold had a core-shell structure and exhibited excellent mechanical properties, hydrophobicity, degradability, and cytocompatibility. Furthermore, in vitro bacterial tests and ex vivo investigations on eardrum infections suggested that this scaffold possesses hyaluronidase-responsive antibacterial properties. It may rapidly release antibiotics when exposed to the enzyme released by S. aureus and P. aeruginosa. These findings suggest that the scaffold has great potential for repairing TMPs with infections.

An interpretable clinical ultrasound-radiomics combined model for diagnosis of stage I cervical cancer.

Objective: The purpose of this retrospective study was to establish a combined model based on ultrasound (US)-radiomics and clinical factors to predict patients with stage I cervical cancer (CC) before surgery. Materials and methods: A total of 209 CC patients who had cervical lesions found by transvaginal sonography (TVS) from the First Affiliated Hospital of Anhui Medical University were retrospectively reviewed, patients were divided into the training set (n = 146) and internal validation set (n = 63), and 52 CC patients from Anhui Provincial Maternity and Child Health Hospital and Nanchong Central Hospital were taken as the external validation set. The clinical independent predictors were selected by univariate and multivariate logistic regression analyses. US-radiomics features were extracted from US images. After selecting the most significant features by univariate analysis, Spearman's correlation analysis, and the least absolute shrinkage and selection operator (LASSO) algorithm, six machine learning (ML) algorithms were used to build the radiomics model. Next, the ability of the clinical, US-radiomics, and clinical US-radiomics combined model was compared to diagnose stage I CC. Finally, the Shapley additive explanations (SHAP) method was used to explain the contribution of each feature. Results: Long diameter of the cervical lesion (L) and squamous cell carcinoma-associated antigen (SCCa) were independent clinical predictors of stage I CC. The eXtreme Gradient Boosting (Xgboost) model performed the best among the six ML radiomics models, with area under the curve (AUC) values in the training, internal validation, and external validation sets being 0.778, 0.751, and 0.751, respectively. In the final three models, the combined model based on clinical features and rad-score showed good discriminative power, with AUC values in the training, internal validation, and external validation sets being 0.837, 0.828, and 0.839, respectively. The decision curve analysis validated the clinical utility of the combined nomogram. The SHAP algorithm illustrates the contribution of each feature in the combined model. Conclusion: We established an interpretable combined model to predict stage I CC. This non-invasive prediction method may be used for the preoperative identification of patients with stage I CC.

Ultrasound contrast-enhanced radiomics model for preoperative prediction of the tumor grade of clear cell renal cell carcinoma: an exploratory study.

BACKGROUND: This study aims to explore machine learning(ML) methods for non-invasive assessment of WHO/ISUP nuclear grading in clear cell renal cell carcinoma(ccRCC) using contrast-enhanced ultrasound(CEUS) radiomics. METHODS: This retrospective study included 122 patients diagnosed as ccRCC after surgical resection. They were divided into a training set (n = 86) and a testing set(n = 36). CEUS radiographic features were extracted from CEUS images, and XGBoost ML models (US, CP, and MP model) with independent features at different phases were established. Multivariate regression analysis was performed on the characteristics of different radiomics phases to determine the indicators used for developing the prediction model of the combined CEUS model and establishing the XGBoost model. The training set was used to train the above four kinds of radiomics models, which were then tested in the testing set. Radiologists evaluated tumor characteristics, established a CEUS reading model, and compared the diagnostic efficacy of CEUS reading model with independent characteristics and combined CEUS model prediction models. RESULTS: The combined CEUS radiomics model demonstrated the best performance in the training set, with an area under the curve (AUC) of 0.84, accuracy of 0.779, sensitivity of 0.717, specificity of 0.879, positive predictive value (PPV) of 0.905, and negative predictive value (NPV) of0.659. In the testing set, the AUC was 0.811, with an accuracy of 0.784, sensitivity of 0.783, specificity of 0.786, PPV of 0.857, and NPV of 0.688. CONCLUSIONS: The radiomics model based on CEUS exhibits high accuracy in non-invasive prediction of ccRCC. This model can be utilized for non-invasive detection of WHO/ISUP nuclear grading of ccRCC and can serve as an effective tool to assist clinical decision-making processes.

Ionic Nitrogen-Doped Carbon Dots as Nonpolar Lubricant Additives at Low Effective Addition.

The poor compatibility with nonpolar lubricant still hinders the application of carbon dots (CDs) in lubrication. In addition, research proves that the existence of ionic structure and active groups on CDs are conducive to their lubricity. In order to obtain the ionic structures and good oil compatibility synchronously, a kind of ionic nitrogen-doped CDs (NCDs) was synthesized via the alkylation of nitrogen in NCDs and anion exchange. The new material could exhibit good tribological performance as poly alpha olefins (PAO4) additives with low addition. Moreover, an ionic liquid, [N44HH][DEHP], with the same anion was chosen as a comparison to investigate the role of NCD cations. The surface analyses demonstrate that NCD cations and phosphate ester anions adsorb on the friction interface to play a synergistic lubrication role during the friction process, which could generate a superior carbon-based tribofilm.

Sweet tea extract encapsulated by different wall material combinations with improved physicochemical properties and bioactivity stability.

Aim: To prepare sweet tea extract microcapsules (STEMs) via a spray-drying by applying different wall material formulations with maltodextrin (MD), inulin (IN), and gum arabic (GA). Methods: The microcapsules were characterised by yield, encapsulation efficiency (EE), particle size, sensory evaluation, morphology, attenuated total reflectance-Fourier transform infra-red spectroscopy and in vitro digestion studies. Results: The encapsulation improved the physicochemical properties and bioactivity stability of sweet tea extract (STE). MD5IN5 had the highest yield (56.33 ± 0.06% w/w) and the best EE (e.g. 88.84 ± 0.36% w/w of total flavonoids). MD9GA1 obtained the smallest particle size (642.13 ± 4.12 nm). MD9GA1 exhibited the highest retention of bioactive components, inhibition of α-glucosidase (96.85 ± 0.55%), α-amylase (57.58 ± 0.99%), angiotensin-converting enzyme (56.88 ± 2.20%), and the best antioxidant activity during in vitro gastrointestinal digestion. Conclusion: The encapsulation of STE can be an appropriate way for the valorisation of STE with improved properties.

Deciphering the Genetic Links between Psychological Stress, Autophagy, and Dermatological Health: Insights from Bioinformatics, Single-Cell Analysis, and Machine Learning in Psoriasis and Anxiety Disorders.

The relationship between psychological stress, altered skin immunity, and autophagy-related genes (ATGs) is currently unclear. Psoriasis is a chronic skin inflammation of unclear etiology that is characterized by persistence and recurrence. Immune dysregulation and emotional disturbances are recognized as significant risk factors. Emerging clinical evidence suggests a possible connection between anxiety disorders, heightened immune system activation, and altered skin immunity, offering a fresh perspective on the initiation of psoriasis. The aim of this study was to explore the potential shared biological mechanisms underlying the comorbidity of psoriasis and anxiety disorders. Psoriasis and anxiety disorders data were obtained from the GEO database. A list of 3254 ATGs was obtained from the public database. Differentially expressed genes (DEGs) were obtained by taking the intersection of DEGs between psoriasis and anxiety disorder samples and the list of ATGs. Five machine learning algorithms used screening hub genes. The ROC curve was performed to evaluate diagnostic performance. Then, GSEA, immune infiltration analysis, and network analysis were carried out. The Seurat and Monocle algorithms were used to depict T-cell evolution. Cellchat was used to infer the signaling pathway between keratinocytes and immune cells. Four key hub genes were identified as diagnostic genes related to psoriasis autophagy. Enrichment analysis showed that these genes are indeed related to T cells, autophagy, and immune regulation, and have good diagnostic efficacy validated. Using single-cell RNA sequencing analysis, we expanded our understanding of key cellular participants, including inflammatory keratinocytes and their interactions with immune cells. We found that the CASP7 gene is involved in the T-cell development process, and correlated with γδ T cells, warranting further investigation. We found that anxiety disorders are related to increased autophagy regulation, immune dysregulation, and inflammatory response, and are reflected in the onset and exacerbation of skin inflammation. The hub gene is involved in the process of immune signaling and immune regulation. The CASP7 gene, which is related with the development and differentiation of T cells, deserves further study. Potential biomarkers between psoriasis and anxiety disorders were identified, which are expected to aid in the prediction of disease diagnosis and the development of personalized treatments.

The role of ZC3H12D-regulated TLR4-NF-κB pathway in LPS-induced pro-inflammatory microglial activation.

Lipopolysaccharide (LPS) is an important neurotoxin that can cause inflammatory activation of microglia. ZC3H12D is a novel immunomodulator, which plays a remarkable role in neurological pathologies. It has not been characterized whether ZC3H12D is involved in the regulation of microglial activation. The aim of this study was to investigate the role of ZC3H12D in LPS-induced pro-inflammatory microglial activation and its potential mechanism. To elucidate this, we established animal models of inflammatory injury by intraperitoneal injection of LPS (10 mg/kg). The results of the open-field test showed that LPS caused impaired motor function in mice. Meanwhile, LPS caused pro-inflammatory activation of microglia in the mice cerebral cortex and inhibited the expression of ZC3H12D. We also constructed in vitro inflammatory injury models by treating BV-2 microglia with LPS (0.5 µg/mL). The results showed that down-regulated ZC3H12D expression was associated with LPS-induced pro-inflammatory microglial activation, and further intervention of ZC3H12D expression could inhibited LPS-induced pro-inflammatory activation of microglia. In addition, LPS activated the TLR4-NF-κB signaling pathway, and this process can also be reversed by promoting ZC3H12D expression. At the same time, the addition of resveratrol, a nutrient previously proven to inhibit pro-inflammatory microglial activation, can also reverse this process by increasing the expression of ZC3H12D. Summarized, our data elucidated that ZC3H12D in LPS-induced pro-inflammatory activation of brain microglia via restraining the TLR4-NF-κB pathway. This study may provide a valuable clue for potential therapeutic targets for neuroinflammation-related injuries.

Relationship between atherosclerotic cardiovascular disease and diabetic retinopathy in patients with type 2 diabetes mellitus.

This study aimed to explore the potential correlation between atherosclerotic cardiovascular disease (ASCVD) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). We enrolled 6540 patients with T2DM who were receiving chronic disease management for hypertension, hyperglycemia, and hyperlipidemia in Chengyang District of Qingdao. Among them, 730 had ASCVD (ASCVD group), which 5810 did not (N-ASCVD group). The results showed significantly higher levels of age, blood glucose, glycosylated hemoglobin (HbA1c), systolic blood pressure, ASCVD family history, female proportion, and DR incidence in the N-ASCVD group. Additionally, the glomerular filtration rate was significantly lower in the ASCVD group. Logistic regression analysis revealed a positive correlation between DR and ASCVD risk. DR was further categorized into 2 subtypes, nonproliferative DR (NPDR) and proliferative DR (PDR), based on e lesion severity. Interestingly, only the PDR was associated with ASCVD. Even after accounting for traditional ASCVD risk factors such as age, sex, and family history, PDR remained associated with ASCVD, with a staggering 718% increase in the risk for patients with PDR. Therefore, there is a strong association between ASCVD and DR in individuals with T2DM, with PDR particularly exhibiting an independent and positive correlation with increased ASCVD risk.

Microenvironment-triggered cascade metal-polyphenolic nanozyme for ROS/NO synergistic hyperglycemic wound healing.

Wound infection of hyperglycemic patient often has extended healing period and increased probability due to the high glucose level. However, achieving precise and safe therapy of the hyperglycemic wound with specific wound microenvironment (WME) remains a major challenge. Herein, a WME-activated smart L-Arg/GOx@TA-Fe (LGTF) nanozymatic system composed of generally recognized as safe (GRAS) compound is engineered. The nanozymatic system combining metal-polyphenol nanozyme (tannic acid-Fe3+, TA-Fe) and natural enzyme (glucose oxidase, GOx) can consume the high-concentration glucose, generating reactive oxygen species (ROS) and nitric oxide (NO) in situ to synergistically disinfect hyperglycemia wound. In addition, glucose consumption and gluconic acid generation can lower glucose level to promote wound healing and reduce the pH of WME to enhance the catalytic activities of the LGTF nanozymatic system. Thereby, low-dose LGTF can perform remarkable synergistic disinfection and healing effect towards hyperglycemic wound. The superior biosafety, high catalytic antibacterial and beneficial WME regulating capacity demonstrate this benign GRAS nanozymatic system is a promising therapeutic agent for hyperglycemic wound.

Revealing microbial community assembly patterns and succession process in the blackening process of black-odor water.

Human-imported pollutants could induce water black, changing microbial community structure and function. Employed 16S rRNA high-throughput sequencing, field-scale investigations and laboratory-scale experiments were successively conducted to reveal mechanistic insights into microbial community assembly and succession of black-odor waters (BOWs). In the field-scale investigation, livestock breeding wastewater (56.7 ± 3.2%) was the most critical microbial source. Moreover, fermentation (27.1 ± 4.4%) was found to be the dominant function. Combined with laboratory experiments, the critical environmental factors, such as total organic carbon (30-100 mg/L), ammonia nitrogen (2.5-9 mg/L), initial dissolved oxygen (2-8 mg/L) and chlorophyll a (0-90 mg/L), impacted the intensity of blackening. The differentiation of ecological niches within the microbial community played a significant role in driving the blackening speed. In laboratory-scale experiments, the microbial ecological niche determined the blackening timing and dominations of the stochastic processes in the microbial assembly process (88 - 51%). The three stages, including the anaerobic degradation stage, blackening stage and slow recovery stage, were proposed to understand the assembly of the microbial communities. These findings enhance our understanding of microorganisms in BOWs and provide valuable insights for detecting and managing heavily organic polluted waters.

Roles of Al and Mg on the Microstructure and Corrosion Resistance of Zn-Al-Mg Hot-Dipped Coated Steel.

In this work, a novel zinc-aluminum-magnesium (Zn-Al-Mg, ZM) coated steel was prepared using the hot-dip method. The microstructure and corrosion resistance of the ZM-coated steel were investigated. Compared to the conventional galvanized steel (GI), the ZM coating demonstrated a distinctive phase structure, consisting of Zn phase, binary eutectic (Zn/MgZn2), and ternary eutectic (Zn/Al/MgZn2). The corrosion resistance of the ZM-coated and GI-coated steels was evaluated by neutral salt spray test (NSST), polarization and electrochemical impedance spectroscopy (EIS). The results indicated that ZM-coated steel provided superior long-term corrosion protection in a NaCl environment compared to GI-coated steel. The scanning vibrating electrode technique (SVET) proved to be an effective method for investigating the evolution of the anodic and cathodic on the local coating surface. GI-coated steel exhibited a potential and current density distribution between the cathodic and anodic sites nearly three orders of magnitude higher than that of ZM-coated steel, suggesting a higher corrosion rate for GI-coated steel.

Gas-Triggered Gate-Opening in a Flexible Three-Dimensional Covalent Organic Framework.

The development of novel soft porous crystals (SPCs) that can be transformed from nonporous to porous crystals is significant because of their promising applications in gas storage and separation. Herein, we systematically investigated for the first time the gas-triggered gate-opening behavior of three-dimensional covalent organic frameworks (3D COFs) with flexible building blocks. FCOF-5, a 3D COF containing C-O single bonds in the backbone, exhibits a unique "S-shaped" isotherm for various gases, such as CO2, C2, and C3 hydrocarbons. According to in situ characterization, FCOF-5 undergoes a pressure-induced closed-to-open structural transition due to the rotation of flexible C-O single bonds in the framework. Furthermore, the gated hysteretic sorption property of FCOF-5 can enable its use as an absorbent for the efficient removal of C3H4 from C3H4/C3H6 mixtures. Therefore, 3D COFs synthesized from flexible building blocks represent a new type of SPC with gate-opening characteristics. This study will strongly inspire us to design other 3D COF-based SPCs for interesting applications in the future.

Ultrasound-based radiomics machine learning models for diagnosing cervical lymph node metastasis in patients with non-small cell lung cancer: a multicentre study.

BACKGROUND: Cervical lymph node metastasis (LNM) is an important prognostic factor for patients with non-small cell lung cancer (NSCLC). We aimed to develop and validate machine learning models that use ultrasound radiomic and descriptive semantic features to diagnose cervical LNM in patients with NSCLC. METHODS: This study included NSCLC patients who underwent neck ultrasound examination followed by cervical lymph node (LN) biopsy between January 2019 and January 2022 from three institutes. Radiomic features were extracted from the ultrasound images at the maximum cross-sectional areas of cervical LNs. Logistic regression (LR) and random forest (RF) models were developed. Model performance was assessed by the area under the curve (AUC) and accuracy, validated internally and externally by fivefold cross-validation and hold-out method, respectively. RESULTS: In total, 313 patients with a median age of 64 years were included, and 276 (88.18%) had cervical LNM. Three descriptive semantic features, including long diameter, shape, and corticomedullary boundary, were selected by multivariate analysis. Out of the 474 identified radiomic features, 9 were determined to fit the LR model, while 15 fit the RF model. The average AUCs of the semantic and radiomics models were 0.876 (range: 0.781-0.961) and 0.883 (range: 0.798-0.966), respectively. However, the average AUC was higher for the semantic-radiomics combined LR model (0.901; range: 0.862-0.927). When the RF algorithm was applied, the average AUCs of the radiomics and semantic-radiomics combined models were improved to 0.908 (range: 0.837-0.966) and 0.922 (range: 0.872-0.982), respectively. The models tested by the hold-out method had similar results, with the semantic-radiomics combined RF model achieving the highest AUC value of 0.901 (95% CI, 0.886-0.968). CONCLUSIONS: The ultrasound radiomic models showed potential for accurately diagnosing cervical LNM in patients with NSCLC when integrated with descriptive semantic features. The RF model outperformed the conventional LR model in diagnosing cervical LNM in NSCLC patients.

A novel g-C3N4-SH@konjac glucomannan composite aerogel for patulin removal from apple juice and its photocatalytic regeneration.

Patulin (PAT) is a hazardous mycotoxin frequently occurs in fruit industry. A reusable g-C3N4-SH@KG composite aerogel for PAT removal in a novel "dark adsorption-light regeneration" mode was prepared by thiol(-SH) functionalization and konjac glucomannan (KG) immobilization. The g-C3N4-SH@KG was characterized by SEM, FT-IR, XPS and UV-Vis DRS, and its PAT adsorption and photocatalytic regeneration behaviors and mechanisms were investigated. The g-C3N4-SH@KG exhibited good regeneration performance, maintaining 83% of PAT initial adsorption capacity (0.92 mg/g) after 5 "adsorption-regeneration" cycles. The adsorption process was endothermic and spontaneous. •OH and h+ generated by photocatalysis were the main substances that degraded PAT into two products and regenerated -SH. The g-C3N4-SH@KG could effectively remove PAT without negative impact on juice quality. The study provided a new strategy for the regeneration of thiol-functionalized PAT adsorbents, and a new idea for the application of non-selective photocatalysis in the control of food contaminations.

B-lymphocyte-induced maturation protein-1 inhibits inflammation and pyroptosis to alleviate sepsis injury.

Liver and lung tissue damage caused by sepsis is still one of the causes of death. B-lymphocyte-induced maturation protein-1 (Blimp-1) has a protective role in inflammation-related disease. However, whether Blimp-1 can regulate cell pyroptosis and affect disease progression in sepsis is still unclear. Animal and cell models were established by the cecal ligation and puncture method and lipopolysaccharides (LPS)-induced RAW 264.7 cells, respectively, and the role of Blimp-1 in regulation inflammatory response and pyroptosis was verified. The changes of inflammation and pyroptosis in liver and lung tissues of septic mice were determined by the addition of TAK-242 (TLR4 inhibitor). Cell pyroptosis and the level of inflammation was detected after Blimp-1 knockdown and TAK-242 treatment in the cell model. The expression of Blimp-1 was continuously increased in a septic mice model. After treatment with TAK-242, the expression of Blimp-1, pyroptosis and inflammatory levels were reduced in mice. In the LPS-induced cell model, cell injury by knockout Blimp-1 was increased, and cell activity was restored after TAK-242 intervention. Overexpression of Blimp-1 relieved LPS-induced cellular inflammatory damage and pyroptosis. Our study had shown that Blimp-1 could improve septic damage by regulating the level of cellular inflammation and pyroptosis in sepsis.

Heimler syndrome with a complaint of blurred vision caused by compound heterozygous variants in PEX1.

INTRODUCTION: Heimler syndrome (HS) is a rare disorder that includes sensorineural hearing loss (SNHL), nail abnormalities, and enamel hypoplasia. Patients with this syndrome can also exhibit ocular manifestations. At present, only a few cases of HS have been reported, existing knowledge of this syndrome is limited, and many cases have been misdiagnosed or even missed. This is the first report of Heimler syndrome with blurred vision as the first complaint, which was diagnosed by genetic analysis in the ophthalmology department. CASE DESCRIPTION: An 8-year-old girl complained of bilateral visual blur and night blindness from birth. Ophthalmic examinations revealed bilateral retinitis pigmentosa with cystoid macular edema, visual impairment with hyperopia and astigmatism. Hearing test revealed bilateral severe sensorineural hearing loss. Dental examinations revealed enamel hypoplasia. In addition, whole-exome sequencing (WES) identified two pathogenic variants in PEX1: the previously reported missense variant c.2966T > C (p.I989 T), and the novel frameshift variant c.1671_1672del (p.G558Sfs*33). CONCLUSION: Heimler syndrome is caused by compound heterozygous PEX1 pathogenic variants, c.2966T > C (p.I989 T) and c.1671_1672del (p.G558Sfs*33), which contributed to the diversity of clinical and genetic profiles in this patient. The main clinical manifestations include bilateral retinitis pigmentosa with cystoid macular edema, sensorineural hearing loss, and enamel hypoplasia. Systemic examinations are suggested for patients suspected of having pigmentary retinal dystrophy, especially combined with hearing-related impairments. Genetic testing can help us to make a definitive diagnosis.

Detecting and characterizing new endofungal bacteria in new hosts: Pandoraea sputorum and Mycetohabitans endofungorum in Rhizopus arrhizus.

The fungus Rhizopus arrhizus (=R. oryzae) is commonly saprotrophic, exhibiting a nature of decomposing organic matter. Additionally, it serves as a crucial starter in food fermentation and can act as a pathogen causing mucormycosis in humans and animals. In this study, two distinct endofungal bacteria (EFBs), associated with individual strains of R. arrhizus, were identified using live/dead staining, fluorescence in situ hybridization, transmission electron microscopy, and 16S rDNA sequencing. The roles of these bacteria were elucidated through antibiotic treatment, pure cultivation, and comparative genomics. The bacterial endosymbionts, Pandoraea sputorum EFB03792 and Mycetohabitans endofungorum EFB03829, were purified from the host fungal strains R. arrhizus XY03792 and XY03829, respectively. Notably, this study marks the first report of Pandoraea as an EFB genus. Compared to its free-living counterparts, P. sputorum EFB03792 exhibited 28 specific virulence factor-related genes, six specific CE10 family genes, and 74 genes associated with type III secretion system (T3SS), emphasizing its pivotal role in invasion and colonization. Furthermore, this study introduces R. arrhizus as a new host for EFB M. endofungorum, with EFB contributing to host sporulation. Despite a visibly reduced genome, M. endofungorum EFB03829 displayed a substantial number of virulence factor-related genes, CE10 family genes, T3SS genes, mobile elements, and significant gene rearrangement. While EFBs have been previously identified in R. arrhizus, their toxin-producing potential in food fermentation has not been explored until this study. The discovery of these two new EFBs highlights their potential for toxin production within R. arrhizus, laying the groundwork for identifying suitable R. arrhizus strains for fermentation processes.