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Biallelic SUFU variants have originally been linked to Joubert syndrome, comprising cerebellar abnormalities, dysmorphism, and polydactyly. In contrast, heterozygous truncating variants have recently been associated with developmental delay and ocular motor apraxia, but only a limited number of patients have been reported. Here, we aim to delineate further the mild end of the phenotypic spectrum related to SUFU haploinsufficiency. Nine individuals (from three unrelated families) harboring truncating SUFU variants were investigated, including two previously reported individuals (from one family). We provide results from a comprehensive assessment comprising neuroimaging, neuropsychology, video-oculography, and genetic testing. We identified three inherited or de novo truncating variants in SUFU (NM_016169.4): c.895C>T p.(Arg299∗), c.71dup p.(Ala25Glyfs∗23), and c.71del p.(Pro24Argfs∗72). The phenotypic expression showed high variability both between and within families. Clinical features include motor developmental delay (seven of nine), axial hypotonia (five of nine), ocular motor apraxia (three of nine), and cerebellar signs (three of nine). Four of the six reported children had macrocephaly. Neuropsychological and developmental assessments revealed mildly delayed language development in the youngest children, whereas general cognition was normal in all variant carriers. Subtle but characteristic SUFU -related neuroimaging abnormalities (including superior cerebellar dysplasia, abnormalities of the superior cerebellar peduncles, rostrally displaced fastigium, and vermis hypoplasia) were observed in seven of nine individuals. Our data shed further light on the mild but recognizable features of SUFU haploinsufficiency and underline its marked phenotypic variability, even within families. Notably, neurodevelopmental and behavioral abnormalities are mild compared with Joubert syndrome and seem to be well compensated over time. [ABSTRACT FROM AUTHOR]

In 2002, heterozygous suppressor of fused variants (SUFU+/−) in the germline were described to have a tumor suppressor role in the development of pediatric medulloblastoma (MB). Other neoplasms associated with pathologic germline SUFU+/− variants have also been described among patients with basal cell nevus syndrome (BCNS; BCNS is also known as Gorlin syndrome, nevoid basal cell carcinoma [BCC] syndrome or Gorlin‐Goltz syndrome; OMIM 109400), an autosomal‐dominant cancer predisposition syndrome. The phenotype of patients with germline SUFU+/− variants is very poorly characterized due to a paucity of large studies with long‐term follow‐up. As such, there is a clinical need to better characterize the spectrum of neoplasms among patients with germline SUFU+/− variants so that clinicians can provide accurate counseling and optimize tumor surveillance strategies. The objective of this study is to perform a scoping review to map the evidence on the rate of medulloblastoma and to describe the spectrum of other neoplasms among patients with germline SUFU+/− variants. A review of all published literature in PubMed (MEDLINE), EMBASE, Cochrane, and Web of Science were searched from the beginning of each respective database until October 9, 2021. Studies of pediatric and adult patients with a confirmed germline SUFU+/− variant who were evaluated for the presence of any neoplasm (benign or malignant) were included. There were 176 patients (N = 30 studies) identified with a confirmed germline SUFU+/− variant who met inclusion criteria. Data were extracted from two cohort studies, two case‐control studies, 18 case series, and eight case reports. The median age at diagnosis of a germline SUFU+/− variant was 4.5 years where 44.4% identified as female and 13.4% of variants were de novo. There were 34 different neoplasms (benign and malignant) documented among patients with confirmed germline SUFU+/− variants, and the most common were medulloblastoma (N = 59 patients), BCC (N = 21 patients), and meningioma (N = 19 patients). The median age at medulloblastoma diagnosis was 1.42 years (range 0.083–3; interquartile range 1.2). When data were available for these three most frequent neoplasms (N = 95 patients), 31 patients (32.6%) had neither MB, BCC nor meningioma; 51 patients (53.7%) had one of medulloblastoma or BCC or meningioma; eight patients (8.4%) had two of medulloblastoma or BCC or meningioma, and five patients (5.3%) had medulloblastoma and BCC and meningioma. This is the first study to synthesize the data on the frequency and spectrum of neoplasms specifically among patients with a confirmed germline SUFU+/− variant. This scoping review is a necessary step forward in optimizing evidence‐based tumor surveillance strategies for medulloblastoma and estimating the risk of other neoplasms that could impact patient outcomes. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of Sufu on lung adenocarcinoma by observing its mutation and the changes in Gli1 transcription after its mutation. Methods cBioPortal for Cancer Genomics was used to obtain the mutation status of Sufu in lung cancer. Four Sufu single base mutation vectors were constructed and transfected into lung adenocarcinoma cell lines A549 and H1975 to establish cells with Sufu overexpression and knockout. Wounding healing assay was employed to determine the effect of Sufu on cell migration, and RT-qPCR, immunofluorescence assay and dual luciferase reporter gene assay were utilized to explore the changes in Gli1 transcription after Sufu mutation. Results cBioPortal data showed that the mutation rate of Sufu in lung cancer was 11.76% in squamous cell carcinoma (2/17), 0.96% in adenocarcinoma (6/625), 1.01% in small cell lung cancer (4/396), and 0.69% in non-small cell lung cancer (77/11 227). The median survival of lung cancer patients was significantly decreased in those with Sufu mutation than those without (38.00 vs 54.34 months, HR=1.943, P < 0.05). A549 cells were sensitive to Sufu knockout, and it resulted in significant increase of the transcription level of Gli1 (P < 0.05). Overexpression of Sufu inhibited cell migration ability in both A549 and H1975 cells (P < 0.05). Sufu mutation had no significant influence on the location of Gli1 in the cells. The Sufu-T411M mutation up-regulated the the transcription level of Gli1 (P < 0.05). Conclusion Sufu has an inhibitory effect on lung adenocarcinoma metastasis, and can be regarded as a potential target for lung adenocarcinoma metastasis.

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Summary: Microscopic, mechanical, physiochemical and colour changes of sufu during fermentation (10, 20, 30, 40, 50, 60 days) were analysed to predict sufu quality objectively and accurately. Fourier transform infrared spectroscopy (FT‐IR) and scanning electron microscopy (SEM) showed that the absorption peaks at 702, 1454, 1652, 2926 and 3281 cm−1 increased in intensity, and sufu was altered from a granular colloidal protein structure to a smooth and uniform shape. Analysis of mechanical, physiochemical and colour properties demonstrated the growth of mucor, the addition of salt and dressing mixture had a significant impact on the changes of indexes of sufu with extension of fermentation time. Besides, a random forest (RF) sufu quality prediction model with 90% accuracy was established by selecting forest quality evaluation indicators using RF and setting the model parameters mtry and ntree to 5 and 900, respectively. [ABSTRACT FROM AUTHOR]

Summary: Sufu, a traditional Chinese fermented soybean food, had its flavour and quality influenced by the specific strains and fermentation environment. To investigate how microbial community succession affects the volatile aroma substances of Mucor racemosus sufu during fermentation, the microbial community structure using high‐throughput sequencing (HTS) technology was analysed. Additionally, volatile flavour compounds using solid‐phase microextraction gas chromatography mass spectrometry (SPME‐GC–MS) were detected. Throughout the pre‐fermentation, salting, and post‐fermentation stages, the changes in the microbial communities over time and space due to environmental variations were observed. The colony compositions at the phylum and genus levels were also analysed. The results revealed that Proteobacteria and Actinobacteria were the dominant bacterial phyla in the final fermented product. Furthermore, several microorganisms associated with flavour substances were identified, such as Lactobacillus, Pseudomonas, Wescheria, Hyphomyces, Candida, and Pichia. These microorganisms primarily influenced the synthesis of alcohols and acids, contributing to the overall flavour profile of the sufu. In the analysis of the final product, it identified fifty‐four volatile flavour compounds, including alcohols, esters, phenolic acids, aldehydes, ketones, ether, alkenes, and other compounds. These findings have important implications for isolating specific strains, enhancing flavour, and providing a solid foundation for optimising and ensuring the quality of sufu. [ABSTRACT FROM AUTHOR]

Summary: Dynamic changes in the flavour quality and microbial composition of sufu in the whole fermentation were studied, and the correlation between them was analyzed. Totally, 135 volatile flavours were identified. The types of volatile substances in sufu ripening for 90 days reached 44, which mainly contributed to volatile components of odour including 1‐octen‐3‐ol (ROAV = 89.89), phenylethyl alcohol (ROAV = 25.05), benzaldehyde (ROAV = 46.82), octanoic acid ethyl ester (ROAV = 49.01) and 2‐pentyl furan (ROAV = 100). Glutamate acid, aspartic acid and 5′‐guanylate contributed significantly to sufu post‐fermentation (TAV >1). The microorganisms in sufu were identified using internal transcribed spacer sequencing technology. The correlations among volatile flavour, taste substances and bacterial community structure were tested via Spearman analysis. Monascus kaoliang promoted the accumulation of most taste components and ethyl ester flavour substances, while Actinomucor elegans inhibited the accumulation of most flavour substances in sufu. This study could potentially help with the rational design of microbial communities to improve sufu quality. [ABSTRACT FROM AUTHOR]

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Gamma-aminobutyric acid (GABA) is an important non-proteinogenic amino acid and a potent bioactive compound with many anti-hypertensive and anti-depressant activities. The bioconversion of GABA by glutamic acid decarboxylase (GAD) has been eagerly studied. Herein, novel pyridoxal-5-phosphate monohydrates (PLP)-dependent GAD, which is not quite similar to reporting, was cloned from Latilactobacillus curvatus and efficiently expressed in E. coli. The conveniently purified GAD (designated LcGAD10s) appeared as a single protein on SDS-PAGE with a molecular mass of 52.0 kDa. LcGAD10s exhibited a specific activity of 303.7 U/mg after purification by Ni–IDA affinity chromatography, with optimal activity at 55 °C and pH 5. LcGAD10s displayed excellent temperature (50 °C) and pH (4–8) stability which relative activity above 80% and 70%, respectively. The enzymatic activity was, respectively, increased and depressed by 130%, and 24% in the presence of Mn+ and Cu2+. Enzyme activity over 90% can be achieved by adding at least 25 mM of PLP. LcGAD10s was able to efficiently transform 15 g/L GABA with a single-factor optimized reaction of pH (5), temperature (50 °C), time (2 h), LcGAD10s dosage (0.4 U) and monosodium glutamate level (5 g/L). Additionally, LcGAD10s can be applied to a tofu fermentation system to achieve GABA conversion and achieved 14.9 mg/g of GABA conversion when added at 2 U/mL, which is higher than most of the commercial sufu and previous application reports, increasing its functional substances. [ABSTRACT FROM AUTHOR]

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Gray sufu, a traditional fermented food derived from soybeans, undergoes a complex fermentation process. This study aimed to investigate the dynamics of the microbial community during sufu fermentation and its relationship with key quality characteristics. Through systematic sampling of sufu at different phases of fermentation, 143 bacterial genera and 84 fungal genera involved in the process were identified. Among these, Chishuiella, Enterococcus, Lactococcus, and Weissella emerged as the predominant bacterial communities. After seven days of ripening fermentation, Trichosporon supplanted Diutina as the predominant fungus, accounting for more than 84% of all fungi. Using redundancy analysis, significant correlations between microbiota and physicochemical properties were uncovered. Chishuiella and Empedobacter displayed positive relationships with pH, soluble protein, and amino nitrogen content. In addition, five biogenic amines were detected, and it was determined that tyramine accounted for more than 75% of the total biogenic amines in the final gray sufu products. Spearman correlation analysis revealed significant positive relationships between Lactococcus, Enterococcus, Tetragenococcus, Halanaerobium, and Trichosporon and the five biogenic amines examined. These findings shed light on the complex interactions between microorganisms and biogenic amines during the fermentation of gray sufu, thereby facilitating the development of microbial regulation strategies for better quality control. [ABSTRACT FROM AUTHOR]

To learn about the diversity of microorganisms in different flavor sufu from different origins in China. Based on high throughput sequencing (HTS), the microbial diversity differences and chemical properties of 16 sufu samples from different origins in China were analyzed in this study. The results of bacterial diversity showed that the most abundant bacteria in sufu were Lactobacillus sp and Bacillus sp, which also represented the dominant bacterial communities in different stages of sufu fermentation. The results of fungal diversity showed that sufu contained a large number of Aspergillus, Actinmucor sp. and other hydrolase producing bacteria. The results of chemical composition determination showed that different origins had certain influence on the chemical composition of sufu. The soluble protein content and amino nitrogen content in curd showed positive correlation with the distribution of Bacillus in the samples. The results of principal coordinate analysis showed that the fungal consortium structure in sufu samples from 16 origins had certain clustering relationship with regions, specifically the fungi from eastern China (ZJ2, ZJ4, ZJ5, ZJ6, SH9, AH11 and JX12) could be grouped together, which stated that the fungal consortium of sufu may be influenced by geographical factors. This study deepened the understanding of microbial community diversity in sufu and would provide theoretical support for the quality improvement of traditional fermented condiments.

In order to investigate the correlation of bacterial community structure and biogenic amines in sufu, Illumina Miseq high-throughput sequencing was used to analyze the bacterial community structure of sufu with different biogenic amines content and relevant environmental factors were determined. The results showed that Firmicutes, Proteobacteria, Actinobacteria and Bacteroidetes were the absolute dominant phyla and the relative abundance of the four phyla were more than 91% in sufu samples. Bacillus, Weissella, Tetragenococcus, and Pseudomonas were the main dominant genera in sufu. The main different genera between high and low biogenic amines content groups were Bacillus, Weissella, Pseudomonas and Lysinibacillus. Correlation analysis showed that biogenic amines and total acid were the main factors affecting bacterial community composition (P

Background: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a cancer biomarker. Furthermore, fusion of the MALAT1 gene with glioma-associated oncogene 1 (GLI1) is a diagnostic marker of plexiform fibromyxoma and gastroblastoma; however, the function of this fusion gene remains unexplored. Method: In this study, we elucidate the structure and function of the MALAT1::GLI1 fusion gene. To this end, we determined a transcriptional start site (TSS) and promoter region for truncated GLI1 expression using rapid amplification of the 5' cDNA end and a luciferase reporter assay in cultured cells transfected with a plasmid harboring the MALAT1::GLI1 fusion gene. Results: We found that the TATA box, ETS1 motif, and TSS were located in MALAT1 and that MALAT1 exhibited transcriptional activity and induced expression of GLI1 from the MALAT1::GLI1 fusion gene. Truncated GLI1, lacking SUMOylation and SUFU binding sites and located in the nucleus, upregulated mRNA expression of GLI1 target genes in the hedgehog signaling pathway. Conclusions: We demonstrate a distinct and alternative function of MALAT1 as a transcriptional promoter for expression of the MALAT1::GLI1 fusion gene. Our findings will aid future research on MALAT1 and its fusion gene partners. [ABSTRACT FROM AUTHOR]

Sufu, a traditional Chinese fermented food, is famous for its unique flavor, especially umami. However, the formation mechanism of its umami peptides is still unclear. Here, we investigated the dynamic change of both umami peptides and microbial communities during sufu production. Based on peptidomic analysis, 9081 key differential peptides were identified, which mainly involved in amino acid transport and metabolism, peptidase activity and hydrolase activity. Twenty-six high-quality umami peptides with ascending trend were recognized by machine learning methods and Fuzzy c-means clustering. Then, through correlation analysis, five bacterial species (Enterococcus italicus, Leuconostoc citreum, L. mesenteroides, L. pseudomesenteroides, Tetragenococcus halophilus) and two fungi species (Cladosporium colombiae, Hannaella oryzae) were identified to be the core functional microorganisms for umami peptides formation. Functional annotation of five lactic acid bacteria indicated their important functions to be carbohydrate metabolism, amino acid metabolism and nucleotide metabolism, which proved their umami peptides production ability. Overall, our results enhanced the understanding of microbial communities and the formation mechanism of umami peptides in sufu, providing novel insights for quality control and flavor improvement of tofu products. [ABSTRACT FROM AUTHOR]

The quality and safety of sufu fermented using Mucor racemosa M2 was studied and compared with naturally fermented sufu. After 90 days post-fermentation, both naturally fermented and inoculated fermented sufu reached the maturity standard of sufu, and the degree of protein hydrolysis of natural sufu (WP/TP: 34% ± 1%; AAN/TN: 33% ± 1%) was slightly higher than that of the inoculated sufu (WP/TP: 28.2% ± 0.4%; AAN/TN: 27% ± 1%). The hardness and adhesiveness of inoculated sufu (Hadness: 1063 g ± 211 g; Adhesiveness: −80 g ± 47 g) were significantly greater than those of natural sufu (Hadness: 790 g ± 57 g; Adhesiveness: −23 g ± 28 g), and the internal structure of natural sufu was denser and more uniform than that of inoculated sufu. A total of 50 aroma compounds were detected in natural and inoculated sufu. The total number of bacterial colonies in naturally fermented sufu was significantly higher than that in inoculated sufu, and the pathogenic bacteria in both types of fermented sufu were lower than the limit of pathogenic bacteria required in fermented soybean products. The content of biogenic amines in sufu was determined by high performance liquid chromatography (HPLC), and the results showed that the content of biogenic amines (Putrescine, Cadaverine, Histamine, Tyramine, etc.) in naturally fermented sufu was significantly higher than that in inoculated fermented sufu. Especially the histamine content, after 90 days of fermentation, was found to be 64.95 ± 4.55 for inoculated fertilization and 44.24 ± 0.71 for natural fertilization. Overall, the quality of inoculated sufu was somewhat better than that of natural sufu, and the M2 strain can be used to ferment sufu. [ABSTRACT FROM AUTHOR]

Genome-wide association studies have identified 10q24.32 as a robust schizophrenia risk locus. Here we identify a regulatory variant (rs10786700) that disrupts binding of transcription factors at 10q24.32. We independently confirmed the association between rs10786700 and schizophrenia in a large Chinese cohort (n = 11 547) and uncovered the biological mechanism underlying this association. We found that rs10786700 resides in a super-enhancer element that exhibits dynamic activity change during the development process and that the risk allele (C) of rs10786700 conferred significant lower enhancer activity through enhancing binding affinity to repressor element-1 silencing transcription factor (REST). CRISPR-Cas9-mediated genome editing identified SUFU as a potential target gene by which rs10786700 might exert its risk effect on schizophrenia, as deletion of rs10786700 downregulated SUFU expression. We further investigated the role of Sufu in neurodevelopment and found that Sufu knockdown inhibited proliferation of neural stem cells and neurogenesis, affected molecular pathways (including neurodevelopment-related pathways, PI3K-Akt and ECM-receptor interaction signalling pathways) associated with schizophrenia and altered the density of dendritic spines. These results reveal that the functional risk single nucleotide polymorphism rs10786700 at 10q24.32 interacts with REST synergistically to regulate expression of SUFU , a novel schizophrenia risk gene which is involved in schizophrenia pathogenesis by affecting neurodevelopment and spine morphogenesis. [ABSTRACT FROM AUTHOR]

Sufu, a traditional fermented soybean product, is a popular side dish in China and other Asian nations. This paper presents an overview of the relationships between the biogenic amines (BAs) of sufu and its processing and storage conditions. Putrescine and cadaverine were found in almost all sufu products. Thus, a BAs-derived formula is proposed to evaluate sufu quality. The use of selected microorganisms as starters reduces the formation of BAs. While, addition of NaCl and alcohol positively delays the formation of BAs by reducing strain and decarboxylase activities. Similarly, lowering the storage temperature and shortening the storage time are practical measures to control activity of bacteria and of decarboxylases. Industrial sufu products require a long storage time, and thus use of additives, particularly natural ones, represents a viable alternative for the control of BAs. [ABSTRACT FROM AUTHOR]

The biogenic amine Level in Jiangxi-made sufu was analyzed by high performance liquid chromatography (HPLC) and amine-producing bacteria were isolated and identified by microbiological methods combined with HPLC confirmation. The results showed that total biogenic amine level ranged from 68.5 to 1084.0 mg/kg in sufu samples. Major biogenic amines were tryptamine, putrescine, histamine and tyramine, among which putrescine and tyramine were of the highest level. Biogenic amine level produced by 9 amine-producing bacteria ranged from 93.8 to 369.2 mg/L. For six bacteria with relatively high amine productivity, phenotype and genotype 16S rDNA sequence determination had found one Bacillus sporothermodurans strain, one Rummeliibacillus stabekisii strain, three Lysinacillus boronitolerans strains and one Staphylococcus piscifermentans strain. The current research offered theoretical evidence for edible safety evaluation of sufu and served as research basis to investigate how to inhibit activity of amine-producing bacteria in sufu.

Simple Summary: In the first sections of this review, we provide a comprehensive description of the Hedgehog signalling pathway in mammals and the main general models of pathway activation. Subsequently, the review focuses on the oncogenic role played by this pathway in rhabdomyosarcoma and the inhibitors developed to date, as well as the clinical trials available in sarcomas. Finally, we provide a discussion and critical review of the results obtained in the clinical setting and their strong dependency on the type of tumour. In some cases, strong discrepancies between encouraging preclinical data and clinical trial results are clearly evident. Aberrant activation of the Hedgehog (Hh) signalling pathway is known to play an oncogenic role in a wide range of cancers; in the particular case of rhabdomyosarcoma, this pathway has been demonstrated to be an important player for both oncogenesis and cancer progression. In this review, after a brief description of the pathway and the characteristics of its molecular components, we describe, in detail, the main activation mechanisms that have been found in cancer, including ligand-dependent, ligand-independent and non-canonical activation. In this context, the most studied inhibitors, i.e., SMO inhibitors, have shown encouraging results for the treatment of basal cell carcinoma and medulloblastoma, both tumour types often associated with mutations that lead to the activation of the pathway. Conversely, SMO inhibitors have not fulfilled expectations in tumours—among them sarcomas—mostly associated with ligand-dependent Hh pathway activation. Despite the controversy existing regarding the results obtained with SMO inhibitors in these types of tumours, several compounds have been (or are currently being) evaluated in sarcoma patients. Finally, we discuss some of the reasons that could explain why, in some cases, encouraging preclinical data turned into disappointing results in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: Suppressor of fused (SuFu) is a tumor-suppressor gene that regulates hedgehog signaling. Its involvement in some malignancies is broadly accepted. However, its association with colorectal cancer (CRC) pathogenesis is not clear. Likewise, no study has clearly associated blood-based inflammatory biomarkers with cancer diagnosis/prognosis as yet. Aim: Our goal was to look at SuFu expression levels in CRC patients and its relationship with other clinicopathological factors. Additionally, we looked into the function of a few blood-based biomarkers in CRC and whether or not a combined strategy at the genetic and clinical levels can be applied in CRC. Methods: The investigation included 98 histopathologically confirmed CRC samples and adjacent normal tissues (controls). A colonoscopy was followed by a targeted biopsy for each suspected colon cancer patient. A CT scan and MRI were also performed on every patient with rectal cancer. Real-time polymerase chain reaction and immunohistochemistry (IHC) were used for assessment. A Beckman Coulter DxH900 was used to examine blood parameters. A Beckman Coulter DxI800 was used to identify pretreatment carcinoma embryonic antigens (CEA) and carbohydrate antigens (CA 19–9) in CRC patients. Results: The expression of SuFu was associated with gender, education, passive smoking, tumor grade, perineural invasion (PNI), lymph node metastasis (LNM), node status, stage, vital status, and recurrence (p < 0.05). In the combined analysis, the areas under the curve produced by the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and red cell distribution width (RDW) were the greatest (AUCRDW+PLR+NLR = 0.91, 95% CI: 0.86–0.93, p < 0.05). Furthermore, the most severe pathological features were linked to RDW, PLR, NLR, and HPR. SuFu expression, node status, LNM, PNI, and stage all had significant correlations with OS and DFS rates in IHC-based univariate survival analysis (p < 0.05). According to the Cox regression, CA-19.9 had a strong independent predictive link with 3-year DFS (p < 0.05). Conclusion: In CRC, SuFu was downregulated both transcriptionally and translationally, was primarily nucleo-cytoplasmic, and was expressed less in high-grade tumors. In addition, SuFu was linked to a poor overall and disease-free survival rate. It may be possible to use SuFu as a therapeutic target for CRC in the future. However, SuFu expression had no effect on RDW, PLR, NLR, or HPR serum levels. [ABSTRACT FROM AUTHOR]

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Objectives: To investigate the benefits of Sufu medical chitosan hydrogel dressing(Sufu) in the prevention and control of radiation skin damage during radiotherapy for cervical cancer as a combined modality. Methods: Ninety-seven cervical cancer patients who underwent radiotherapy at the Cancer Hospital of China Medical University between May 2017 and November 2018 were recruited according to given inclusion and exclusion criteria. The patients were assigned to a control group (n=48, washing the perineal area with normal saline) and an observation group (n=49, application of Sufu onto the site of radiotherapy in addition to washing the perineal area with normal saline). The treatment regimens for the two groups continued until the end of radiotherapy. A comparison of the RTOG (Radiation Therapy Oncology Group) grading of acute radiation-induced skin reactions (ARISRs), pain intensity (measured by the verbal rating scale (VRS)) and post-treatment wound healing was drawn between the two groups. Results: In the observation group, 81.6% (40/49) of the patients had radiation dermatitis, which was significantly lower than the incidence rate (95.8%, 46/48) in the control group (P <0.05). The observation group was at higher risk of radiation dermatitis when given a high radiation dose, while the control group was more likely to have radiation dermatitis when administered with a moderate radiation dose (P <0.05). The median time of occurrence of pain and the median time of onset of skin reactions were significantly later in the observation group as compared with the control group (P <0.05, respectively). In the observation group, the pain relief rate was 92.50% at Day-3, and the wound healing rate was 95.0% at Day-7, significantly higher than in the control group (73.9% and 80.4%) (P <0.05, respectively). Conclusions: During radiotherapy for cervical cancer, Sufu can effectively prevent and control radiationinduced skin and mucous membrane damage, delay the onset of radiation dermatitis and substantially reduce the incidence rate, relieve radiation dermatitis and pain and promote wound healing. [ABSTRACT FROM AUTHOR]

Copyright of China Brewing is the property of China Brewing Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Development of mammalian auditory epithelium, the organ of Corti, requires precise control of both cell cycle withdrawal and differentiation. Sensory progenitors (prosensory cells) in the cochlear apex exit the cell cycle first but differentiate last. Sonic hedgehog (Shh) signaling is required for the spatiotemporal regulation of prosensory cell differentiation, but the underlying mechanisms remain unclear. Here, we show that suppressor of fused (Sufu), a negative regulator of Shh signaling, is essential for controlling the timing and progression of hair cell (HC) differentiation. Removal of Sufu leads to abnormal Atoh1 expression and a severe delay of HC differentiation due to elevated Gli2 mRNA expression. Later in development, HC differentiation defects are restored in the Sufu mutant by the action of speckle-type PDZ protein (Spop), which promotes Gli2 protein degradation. Deletion of both Sufu and Spop results in robust Gli2 activation, exacerbating HC differentiation defects. We further demonstrate that Gli2 inhibits HC differentiation through maintaining the progenitor state of Sox2+ prosensory cells. Along the basal-apical axis of the developing cochlea, the Sox2 expression level is higher in the progenitor cells than in differentiating cells and is down-regulated from base to apex as differentiation proceeds. The dynamic spatiotemporal change of Sox2 expression levels is controlled by Shh signaling through Gli2. Together, our results reveal key functions of Gli2 in sustaining the progenitor state, thereby preventing HC differentiation and in turn governing the basal-apical progression of HC differentiation in the cochlea. [ABSTRACT FROM AUTHOR]

Background: Congenital medulloblastoma is very rare, and many cases involve germline mutations that can lead to inherited syndromes. Here, we first report two brothers with congenital medulloblastoma who were diagnosed with Gorlin-Goltz syndrome caused by SUFU mutation. Clinical presentation: Medulloblastoma was detected in two brothers at 2 and 3 months of age, with very similar imaging features. Genetic testing revealed that both children and their mother carried SUFU gene germline mutations, and both brothers were diagnosed with Gorlin-Goltz syndrome. Conclusion: Gorlin-Goltz syndrome-associated congenital medulloblastoma with SUFU germline mutation is very rare. Pathological types mostly involve desmoplastic/nodular or extensive nodularity; chemotherapy is the main treatment, and studies revealing prognostic data are scarce. [ABSTRACT FROM AUTHOR]

This study was to investigate dynamic changes of microbial communities, physicochemical parameters, enzyme activities, tastes and volatile flavor compounds of sufu fermented by different starters during sufu fermentation. The results showed that sufu inoculated starter cultures B (MSC-B) consisted of Rhizopus oligosporus, Mucor 40,899, Saccharomyces cerevisiae and Lactobacillus bulgaricus with a ratio of 4:2:2:1 had higher contents of soluble protein and amino nitrogen as well as superior activity of protease, glucoamylase and lipase. Correlation analysis demonstrated that the three starters were significantly positive correlated with total acid, amino acid nitrogen and soluble protein. In addition, using MSC-B to produce sufu, aspartic increased by 17.5-fold. Moreover, fruity smell and burnt sugar flavor were the key volatile flavor compounds for sufu fermented by MSC-B in the pre-fermentation. Alcohols became the predominant volatile flavor compounds in the post-fermentation for the three starter cultures. In conclusion, MSC-B is of great potential in the application of sufu industry. Our work will provide a theoretical reference for the development of new mixed - starter cultures in sufu.

BackgroundCongenital medulloblastoma is very rare, and many cases involve germline mutations that can lead to inherited syndromes. Here, we first report two brothers with congenital medulloblastoma who were diagnosed with Gorlin-Goltz syndrome caused by SUFU mutation.Clinical presentationMedulloblastoma was detected in two brothers at 2 and 3 months of age, with very similar imaging features. Genetic testing revealed that both children and their mother carried SUFU gene germline mutations, and both brothers were diagnosed with Gorlin-Goltz syndrome.ConclusionGorlin-Goltz syndrome-associated congenital medulloblastoma with SUFU germline mutation is very rare. Pathological types mostly involve desmoplastic/nodular or extensive nodularity; chemotherapy is the main treatment, and studies revealing prognostic data are scarce.

Gamma-aminobutyric acid (GABA) is an important non-proteinogenic amino acid and a potent bioactive compound with many anti-hypertensive and anti-depressant activities. The bioconversion of GABA by glutamic acid decarboxylase (GAD) has been eagerly studied. Herein, novel pyridoxal-5-phosphate monohydrates (PLP)-dependent GAD, which is not quite similar to reporting, was cloned from Latilactobacillus curvatus and efficiently expressed in E. coli. The conveniently purified GAD (designated LcGAD10s) appeared as a single protein on SDS-PAGE with a molecular mass of 52.0 kDa. LcGAD10s exhibited a specific activity of 303.7 U/mg after purification by Ni–IDA affinity chromatography, with optimal activity at 55 °C and pH 5. LcGAD10s displayed excellent temperature (50 °C) and pH (4–8) stability which relative activity above 80% and 70%, respectively. The enzymatic activity was, respectively, increased and depressed by 130%, and 24% in the presence of Mn+ and Cu2+. Enzyme activity over 90% can be achieved by adding at least 25 mM of PLP. LcGAD10s was able to efficiently transform 15 g/L GABA with a single-factor optimized reaction of pH (5), temperature (50 °C), time (2 h), LcGAD10s dosage (0.4 U) and monosodium glutamate level (5 g/L). Additionally, LcGAD10s can be applied to a tofu fermentation system to achieve GABA conversion and achieved 14.9 mg/g of GABA conversion when added at 2 U/mL, which is higher than most of the commercial sufu and previous application reports, increasing its functional substances.

Gray sufu, a traditional fermented food derived from soybeans, undergoes a complex fermentation process. This study aimed to investigate the dynamics of the microbial community during sufu fermentation and its relationship with key quality characteristics. Through systematic sampling of sufu at different phases of fermentation, 143 bacterial genera and 84 fungal genera involved in the process were identified. Among these, Chishuiella, Enterococcus, Lactococcus, and Weissella emerged as the predominant bacterial communities. After seven days of ripening fermentation, Trichosporon supplanted Diutina as the predominant fungus, accounting for more than 84% of all fungi. Using redundancy analysis, significant correlations between microbiota and physicochemical properties were uncovered. Chishuiella and Empedobacter displayed positive relationships with pH, soluble protein, and amino nitrogen content. In addition, five biogenic amines were detected, and it was determined that tyramine accounted for more than 75% of the total biogenic amines in the final gray sufu products. Spearman correlation analysis revealed significant positive relationships between Lactococcus, Enterococcus, Tetragenococcus, Halanaerobium, and Trichosporon and the five biogenic amines examined. These findings shed light on the complex interactions between microorganisms and biogenic amines during the fermentation of gray sufu, thereby facilitating the development of microbial regulation strategies for better quality control.

Sufu, a Chinese traditional fermented soybean product, has a characteristic foul smell but a pleasant taste. We determined the core functional microbiota and their metabolic mechanisms during sufu fermentation by examining relationships among bacteria, characteristic flavor compounds, and physicochemical factors. Flavor compounds in sufu were detected through headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry, and the microbial community structure was determined through high-throughput 16S rRNA sequencing. The results showed that the fermentation process of sufu could be divided into early and late stages. The early stage was critical for flavor development. Seven microbiota were screened based on their abundance, microbial relevance, and flavor production capacity. Five microbes were screened in the early stage: Pseudomonas, Tetragenococcus, Lysinibacillus, Pantoea, and Burkholderia–Caballeronia–Paraburkholderia. Three microbes were screened in the late stage: Exiguobacterium, Bacillus, and Pseudomonas. Their metabolic profiles were predicted. The results provided a reference for the selection of enriched bacterial genera in the fermentation process and controlling applicable process conditions to improve the flavor of sufu. [ABSTRACT FROM AUTHOR]

Abstract Background Local ischemia and defective osteogenesis are implicated in the progression of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Recent studies have revealed that exosomes released from adipose-derived stem cells (ASCs) play important roles in ONFH therapy. The present study aimed to investigate whether exosomes derived from miR-378-overexpressing ASCs (miR-378-ASCs-Exos) could promote angiogenesis and osteogenesis in GC-induced ONFH. Methods In vitro, we investigated the osteogenic potential of miR-378-ASCs-Exos on bone marrow stromal cells (BMSCs) by alkaline phosphatase staining and western blotting. The angiogenic effects of miR-378-ASCs-Exos on human umbilical vein endothelial cells (HUVECs) were examined by evaluating their proliferation, migration, and tube-forming analyses. We identified the underlying mechanisms of miR-378 in osteogenic and angiogenic regulation. In addition, an ONFH rat model was established to explore the effects of miR-378-ASCs-Exos through histological and immunohistochemical staining and micro-CT in vivo. Results Administration of miR-378-ASCs-Exos improved the osteogenic and angiogenic potentials of BMSCs and HUVECs. miR-378 negatively regulated the suppressor of fused (Sufu) and activated Sonic Hedgehog (Shh) signaling pathway, and recombinant Sufu protein reduced the effects triggered by miR-378-ASCs-Exos. In vivo experiments indicated that miR-378-ASCs-Exos markedly accelerated bone regeneration and angiogenesis, which inhibited the progression of ONFH. Conclusion Our study indicated that miR-378-ASCs-Exos enhances osteogenesis and angiogenesis by targeting Sufu to upregulate the Shh signaling pathway, thereby attenuating GC-induced ONFH development.

Sufu, a traditional fermented soybean product, known for its cheese-like texture, has not been extensively studied regarding the mechanisms responsible for the formation of this unique texture in sufu gels. In order to explore this phenomenon, an analysis was conducted on the texture, physicochemical properties, and microstructure of sufu gels fermented by mucor racemosus at different intervals. The findings indicated no significant difference in water holding capacity (WHC) of sufu gel at 0 h, 24 h, and 48 h, but a notable increase in WHC was observed at 72 h and 96 h (p<0.05). The hardness of sufu gel at 72 h and 96 h was found to be low, with values of 4.8 ± 0.56 N and 4.99 ± 0.54 N, respectively, indicating a soft texture of sufu. The peak of protease activity at 48 h was 38.19 U/g. Following fermentation for 24 h and 48 h, the secondary structure of sufu gel was predominantly composed of β-sheet, while α-helix was the primary secondary structure at 72 h and 96 h. Analysis using the scanning electron microscope (SEM) and confocal laser scanning microscopy (CLSM) analysis revealed the network-like structures present in sufu gel. These findings offer valuable insights for enhancing gel properties and sensory characteristics. • Protease activity reached the peak value at 48 h. • Mucor racemosus fermentation changed the secondary structure of sufu gels. • Sufu gels fermented at 48 h possessing the smoothest and flattest surface. • The density of sufu gels were gradually increasing from 0 h to 96 h. [ABSTRACT FROM AUTHOR]

Iron-sulfur (Fe-S) clusters are inorganic prosthetic groups in proteins composed exclusively of iron and inorganic sulfide. These cofactors are required in a wide range of critical cellular pathways. Iron-sulfur clusters do not form spontaneously in vivo; several proteins are required to mobilize sulfur and iron, assemble and traffic-nascent clusters. Bacteria have developed several Fe-S assembly systems, such as the ISC, NIF, and SUF systems. Interestingly, in Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), the SUF machinery is the primary Fe-S biogenesis system. This operon is essential for the viability of Mtb under normal growth conditions, and the genes it contains are known to be vulnerable, revealing the Mtb SUF system as an interesting target in the fight against tuberculosis. In the present study, two proteins of the Mtb SUF system were characterized for the first time: Rv1464(sufS) and Rv1465(sufU). The results presented reveal how these two proteins work together and thus provide insights into Fe-S biogenesis/metabolism by this pathogen. Combining biochemistry and structural approaches, we showed that Rv1464 is a type II cysteine-desulfurase enzyme and that Rv1465 is a zinc-dependent protein interacting with Rv1464. Endowed with a sulfurtransferase activity, Rv1465 significantly enhances the cysteine-desulfurase activity of Rv1464 by transferring the sulfur atom from persulfide on Rv1464 to its conserved Cys40 residue. The zinc ion is important for the sulfur transfer reaction between SufS and SufU, and His354 in SufS plays an essential role in this reaction. Finally, we showed that Mtb SufS-SufU is more resistant to oxidative stress than E. coli SufS-SufE and that the presence of zinc in SufU is likely responsible for this improved resistance. This study on Rv1464 and Rv1465 will help guide the design of future anti-tuberculosis agents.

The quality and safety of sufu fermented using Mucor racemosa M2 was studied and compared with naturally fermented sufu. After 90 days post-fermentation, both naturally fermented and inoculated fermented sufu reached the maturity standard of sufu, and the degree of protein hydrolysis of natural sufu (WP/TP: 34% ± 1%; AAN/TN: 33% ± 1%) was slightly higher than that of the inoculated sufu (WP/TP: 28.2% ± 0.4%; AAN/TN: 27% ± 1%). The hardness and adhesiveness of inoculated sufu (Hadness: 1063 g ± 211 g; Adhesiveness: −80 g ± 47 g) were significantly greater than those of natural sufu (Hadness: 790 g ± 57 g; Adhesiveness: −23 g ± 28 g), and the internal structure of natural sufu was denser and more uniform than that of inoculated sufu. A total of 50 aroma compounds were detected in natural and inoculated sufu. The total number of bacterial colonies in naturally fermented sufu was significantly higher than that in inoculated sufu, and the pathogenic bacteria in both types of fermented sufu were lower than the limit of pathogenic bacteria required in fermented soybean products. The content of biogenic amines in sufu was determined by high performance liquid chromatography (HPLC), and the results showed that the content of biogenic amines (Putrescine, Cadaverine, Histamine, Tyramine, etc.) in naturally fermented sufu was significantly higher than that in inoculated fermented sufu. Especially the histamine content, after 90 days of fermentation, was found to be 64.95 ± 4.55 for inoculated fertilization and 44.24 ± 0.71 for natural fertilization. Overall, the quality of inoculated sufu was somewhat better than that of natural sufu, and the M2 strain can be used to ferment sufu.

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Abstract Background The regulator of cullins-1 (ROC1) is an essential subunit in the cullin-RING ligase (CRL) protein complex and has been shown to be critical in bladder cancer cell survival and progression. This study aimed to explore the molecular mechanism of ROC1 action in the malignant progression of bladder cancer. Methods This study utilized ex vivo, in vitro, and in vivo nude mouse experiments to assess the underlying mechanisms of ROC1 in bladder cancer cells. The expression of the components of the sonic hedgehog (SHH) pathway was determined by western blot analysis. ROC1 expression in human tumors was evaluated by immunohistochemistry. Results ROC1 overexpression promoted the growth of bladder cancer cells, whereas knockdown of ROC1 expression had the opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target suppressor of fused homolog (SUFU) for ubiquitin-dependent degradation, allowing Gli2 release from the SUFU complex to activate the SHH pathway. Furthermore, knockdown of SUFU expression partially rescued the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. In ex vivo experiments, tissue microarray analysis of human bladder cancer specimens revealed a positive association of ROC1 expression with the SHH pathway activity. Conclusion This study demonstrated that dysregulation of the ROC1–SUFU–GLI2 axis plays an important role in bladder cancer progression and that targeting ROC1 expression is warranted in further investigations as a novel strategy for the future control of bladder cancer.

Sufu is a pleasant-tasting, traditional Chinese fermented soybean food that is rich in nutrients. In this study, the changes of volatile and nonvolatile metabolites in sufu fermented by bacillus licheniformis, were investigated. The results indicated that a total of 55 kinds of nonvolatile compounds were detected, including 2 carbohydrates, 4 alcohols, 17 amino acids, 18 organic acids, 6 biogenic amines, and 8 other substances. Furthermore, a total of 58 volatile compounds identified were composed of 11 esters, 16 alcohols, 10 acids, and 21 miscellaneous compounds. Inoculation of bacillus licheniformis enriched the metabolite profile of sufu and improved its functionality and safety of edibility. It was observed that the pure fermented starter resulted in controlled acceleration of sufu maturation.

Background: Suppressor of fused (SuFu) is a tumor-suppressor gene that regulates hedgehog signaling. Its involvement in some malignancies is broadly accepted. However, its association with colorectal cancer (CRC) pathogenesis is not clear. Likewise, no study has clearly associated blood-based inflammatory biomarkers with cancer diagnosis/prognosis as yet. Aim: Our goal was to look at SuFu expression levels in CRC patients and its relationship with other clinicopathological factors. Additionally, we looked into the function of a few blood-based biomarkers in CRC and whether or not a combined strategy at the genetic and clinical levels can be applied in CRC. Methods: The investigation included 98 histopathologically confirmed CRC samples and adjacent normal tissues (controls). A colonoscopy was followed by a targeted biopsy for each suspected colon cancer patient. A CT scan and MRI were also performed on every patient with rectal cancer. Real-time polymerase chain reaction and immunohistochemistry (IHC) were used for assessment. A Beckman Coulter DxH900 was used to examine blood parameters. A Beckman Coulter DxI800 was used to identify pretreatment carcinoma embryonic antigens (CEA) and carbohydrate antigens (CA 19–9) in CRC patients. Results: The expression of SuFu was associated with gender, education, passive smoking, tumor grade, perineural invasion (PNI), lymph node metastasis (LNM), node status, stage, vital status, and recurrence (p < 0.05). In the combined analysis, the areas under the curve produced by the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and red cell distribution width (RDW) were the greatest (AUCRDW+PLR+NLR = 0.91, 95% CI: 0.86–0.93, p < 0.05). Furthermore, the most severe pathological features were linked to RDW, PLR, NLR, and HPR. SuFu expression, node status, LNM, PNI, and stage all had significant correlations with OS and DFS rates in IHC-based univariate survival analysis (p < 0.05). According to the Cox regression, CA-19.9 had a strong independent predictive link with 3-year DFS (p < 0.05). Conclusion: In CRC, SuFu was downregulated both transcriptionally and translationally, was primarily nucleo-cytoplasmic, and was expressed less in high-grade tumors. In addition, SuFu was linked to a poor overall and disease-free survival rate. It may be possible to use SuFu as a therapeutic target for CRC in the future. However, SuFu expression had no effect on RDW, PLR, NLR, or HPR serum levels.

Background: Mesothelioma is a rare and aggressive malignant neoplasm arising from mesothelial cells, which occasionally manifests recurrent fusions. EWSR1/FUS-CREB, YY1, MAP3K8, NR4A3, and ALK-rearranged proliferations have been reported in limited series with no clear histological or clinical correlations, limiting clinicians' ability to assess prognosis and integrate these new entities into therapeutic decisions. The aim of this study was to better characterize these rearranged proliferations histologically, molecularly, and clinically., Methods: Clinical, pathological, and comprehensive transcriptome and mutation data were collected for each case., Results: A total of 41 tumors were included, encompassing 7 ALK, 10 MAP3K8, 4 NR4A3, 8 ESWR1/FUS::ATF1, 8 EWSR1::YY1, and 4 SUFU-fused cases. We found a female predominance, except for cases harboring NR4A3 and SUFU; and most patients were around 60 years of age, but those harboring ALK or EWSR1/FUS::ATF1 gene fusions were younger. Each group exhibited distinct histological, immunohistochemical, molecular features, and oncological courses. Specifically, MAP3K8 and ALK presented PAX8+ papillary proliferations, ESWR1/FUS::ATF1 and EWSR1::YY1 displayed angiomatoid fibrous histiocytoma-like patterns, while SUFU showcased 'tissue culture'-like spindle cell proliferation. Poor prognosis factors were the pleural site, male sex, Ki67 ≥10%, and ESWR1/FUS::ATF1 or SUFU gene fusions., Conclusions: This study significantly broadens the spectrum of mesothelial tumors associated with fusions, offering insight into novel epithelioid (mesothelial) proliferations with distinctive histological appearances, molecular profiles, and prognoses to guide adapted treatments for patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Gorlin syndrome is a genetic condition associated with the occurrence of SHH activated medulloblastoma, basal cell carcinoma, macrocephaly and other congenital anomalies. It is caused by heterozygous pathogenic variants in PTCH1 or SUFU. In this study we included 16 patients from the HIT2000, HIT2000interim, I-HIT-MED, observation registry and older registries such as HIT-SKK87, HIT-SKK92 (1987 – 2020) with genetically confirmed Gorlin syndrome, harboring 10 PTCH1 and 6 SUFU mutations. Nine patients presented with desmoplastic medulloblastomas (DMB), 6 with medulloblastomas with extensive nodularity (MBEN) and one patient with classic medulloblastoma (CMB); all tumors affected the cerebellum, vermis or the fourth ventricle. SHH activation was present in all investigated tumors (14/16); DNA methylation analysis (when available) classified 3 tumors as iSHH-I and 4 tumors as iSHH-II. Age at diagnosis ranged from 0.65 to 3.41 years. All but one patient received chemotherapy according to the HIT-SKK protocol. Ten patients were in complete remission after completion of primary therapy; four subsequently presented with PD. No patient received radiotherapy during initial treatment. Five patients acquired additional neoplasms, namely basal cell carcinomas, odontogenic tumors, ovarian fibromas and meningioma. Developmental delay was documented in 5/16 patients. Overall survival (OS) and progression-free survival (PFS) between patients with PTCH1 or SUFU mutations did not differ statistically (10y-OS 90% vs. 100%, p=0.414; 5y-PFS 88.9% ± 10.5% vs. 41.7% ± 22.2%, p=0.139). Comparing the Gorlin patients to all young, SHH activated MBs in the registries (10y-OS 93.3% ± 6.4% vs. 92.5% ± 3.3%, p=0.738; 10y-PFS 64.9%+-16.7% vs. 83.8%+-4.5%, p=0.228) as well as comparing Gorlin M0 SKK-treated patients to all young, SHH activated, M0, SKK-treated MBs in the HIT-MED database did not reveal significantly different clinical outcomes (10y-OS 88.9% ± 10.5% vs. 88% ± 4%, p=0.812; 5y-PFS 87.5% ± 11.7% vs. 77.7% ± 5.1%, p=0.746). Gorlin syndrome should be considered in young children with SHH activated medulloblastoma, especially DMB and MBEN but cannot be ruled out for CMB. Survival did not differ to patients with SHH-activated medulloblastoma with unknown germline status or between PTCH1 and SUFU mutated patients. Additional neoplasms, especially basal cell carcinomas, need to be expected and screened for. Genetic counselling should be provided for families with young medulloblastoma patients with SHH activation. [ABSTRACT FROM AUTHOR]

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Gorlin syndrome (MIM 109,400), a cancer predisposition syndrome related to a constitutional pathogenic variation (PV) of a gene in the Sonic Hedgehog pathway (PTCH1 or SUFU), is associated with a broad spectrum of benign and malignant tumors. Basal cell carcinomas (BCC), odontogenic keratocysts and medulloblastomas are the main tumor types encountered, but meningiomas, ovarian or cardiac fibromas and sarcomas have also been described. The clinical features and tumor risks are different depending on the causative gene. Due to the rarity of this condition, there is little data on phenotype-genotype correlations. This report summarizes genotype-based recommendations for screening patients with PTCH1 and SUFU-related Gorlin syndrome, discussed during a workshop of the Host Genome Working Group of the European branch of the International Society of Pediatric Oncology (SIOPE HGWG) held in January 2020. In order to allow early detection of BCC, dermatologic examination should start at age 10 in PTCH1, and at age 20 in SUFU PV carriers. Odontogenic keratocyst screening, based on odontologic examination, should begin at age 2 with annual orthopantogram beginning around age 8 for PTCH1 PV carriers only. For medulloblastomas, repeated brain MRI from birth to 5 years should be proposed for SUFU PV carriers only. Brain MRI for meningiomas and pelvic ultrasound for ovarian fibromas should be offered to both PTCH1 and SUFU PV carriers. Follow-up of patients treated with radiotherapy should be prolonged and thorough because of the risk of secondary malignancies. Prospective evaluation of evidence of the effectiveness of these surveillance recommendations is required. [ABSTRACT FROM AUTHOR]

Gorlin syndrome is a genetic condition associated with the occurrence of SHH activated medulloblastoma, basal cell carcinoma, macrocephaly and other congenital anomalies. It is caused by heterozygous pathogenic variants in PTCH1 or SUFU. In this study we included 16 patients from the HIT2000, HIT2000interim, I-HIT-MED, observation registry and older registries such as HIT-SKK87, HIT-SKK92 (1987 – 2020) with genetically confirmed Gorlin syndrome, harboring 10 PTCH1 and 6 SUFU mutations. Nine patients presented with desmoplastic medulloblastomas (DMB), 6 with medulloblastomas with extensive nodularity (MBEN) and one patient with classic medulloblastoma (CMB); all tumors affected the cerebellum, vermis or the fourth ventricle. SHH activation was present in all investigated tumors (14/16); DNA methylation analysis (when available) classified 3 tumors as iSHH-I and 4 tumors as iSHH-II. Age at diagnosis ranged from 0.65 to 3.41 years. All but one patient received chemotherapy according to the HIT-SKK protocol. Ten patients were in complete remission after completion of primary therapy; four subsequently presented with PD. No patient received radiotherapy during initial treatment. Five patients acquired additional neoplasms, namely basal cell carcinomas, odontogenic tumors, ovarian fibromas and meningioma. Developmental delay was documented in 5/16 patients. Overall survival (OS) and progression-free survival (PFS) between patients with PTCH1 or SUFU mutations did not differ statistically (10y-OS 90% vs. 100%, p=0.414; 5y-PFS 88.9% ± 10.5% vs. 41.7% ± 22.2%, p=0.139). Comparing the Gorlin patients to all young, SHH activated MBs in the registries (10y-OS 93.3% ± 6.4% vs. 92.5% ± 3.3%, p=0.738; 10y-PFS 64.9%+-16.7% vs. 83.8%+-4.5%, p=0.228) as well as comparing Gorlin M0 SKK-treated patients to all young, SHH activated, M0, SKK-treated MBs in the HIT-MED database did not reveal significantly different clinical outcomes (10y-OS 88.9% ± 10.5% vs. 88% ± 4%, p=0.812; 5y-PFS 87.5% ± 11.7% vs. 77.7% ± 5.1%, p=0.746). Gorlin syndrome should be considered in young children with SHH activated medulloblastoma, especially DMB and MBEN but cannot be ruled out for CMB. Survival did not differ to patients with SHH-activated medulloblastoma with unknown germline status or between PTCH1 and SUFU mutated patients. Additional neoplasms, especially basal cell carcinomas, need to be expected and screened for. Genetic counselling should be provided for families with young medulloblastoma patients with SHH activation.

The process of soybean fermentation has been practiced for more than 3,000 years. Although Dajiang and Sufu are two popular fermented soybean products consumed in North China, limited information is available regarding their microbial composition. Hence, the current study sought to investigate, and compare, the physicochemical indicators and microbial communities of traditional Dajiang and Sufu. Results showed that the titratable acidity (TA), and salinity, as well as the lactic acid, and malic acid contents were significantly higher in Sufu samples compared to Dajiang. Furthermore, Sufu samples contain abundant sucrose and fructose, while the acetic acid content was lower in Sufu compared to Dajiang samples. Moreover, the predominant bacterial phyla in Dajiang and Sufu samples were Firmicutes and Proteobacteria, while the major genera comprise Bacillus, Lactobacillus, Tetragenococcus, and Weissella. Moreover, Dajiang samples also contained abundant Pseudomonas, and Brevundimonas spp., while Halomonas, Staphylococcus, Lysinibacillus, Enterobacter, Streptococcus, Acinetobacter, and Halanaerobium spp. were abundant in Sufu samples. At the species level, Bacillus velezensis, Tetragenococcus halophilus, Lactobacillus rennini, Weissella cibaria, Weissella viridescens, Pseudomonas brenneri, and Lactobacillus acidipiscis represented the major species in Dajiang, while Halomonas sp., Staphylococcus equorum, and Halanaerobium praevalens were the predominant species in Sufu. Acetic acid and sucrose were found to be the primary major physicochemical factor influencing the bacterial communities in Dajiang and Sufu, respectively. Furthermore, Bacillus subtilis is strongly correlated with lactic acid levels, L. acidipiscis is positively correlated with acetic acid levels, while Staphylococcus sciuri and S. equorum are strongly, and positively, correlated with malic acid. Following analysis of carbohydrate and amino acid metabolism in all samples, cysteine and methionine metabolism, as well as fatty acid biosynthesis-related genes are upregulated in Dajiang compared to Sufu samples. However, such as the Staphylococcus, W. viridescens, and P. brenneri, as potentially foodborne pathogens, existed in Dajang and Sufu samples. Cumulatively, these results suggested that Dajiang and Sufu have unique bacterial communities that influence their specific characteristics. Hence, the current study provides insights into the microbial community composition in Dajiang and Sufu samples, which may facilitate the isolation of functional bacterial species suitable for Dajiang and Sufu production, thus improving their production efficiency.

The process of soybean fermentation has been practiced for more than 3,000 years. Although Dajiang and Sufu are two popular fermented soybean products consumed in North China, limited information is available regarding their microbial composition. Hence, the current study sought to investigate, and compare, the physicochemical indicators and microbial communities of traditional Dajiang and Sufu. Results showed that the titratable acidity (TA), and salinity, as well as the lactic acid, and malic acid contents were significantly higher in Sufu samples compared to Dajiang. Furthermore, Sufu samples contain abundant sucrose and fructose, while the acetic acid content was lower in Sufu compared to Dajiang samples. Moreover, the predominant bacterial phyla in Dajiang and Sufu samples were Firmicutes and Proteobacteria, while the major genera comprise Bacillus , Lactobacillus , Tetragenococcus , and Weissella. Moreover, Dajiang samples also contained abundant Pseudomonas , and Brevundimonas spp., while Halomonas , Staphylococcus , Lysinibacillus , Enterobacter , Streptococcus , Acinetobacter , and Halanaerobium spp. were abundant in Sufu samples. At the species level, Bacillus velezensis , Tetragenococcus halophilus , Lactobacillus rennini , Weissella cibaria , Weissella viridescens , Pseudomonas brenneri , and Lactobacillus acidipiscis represented the major species in Dajiang, while Halomonas sp., Staphylococcus equorum , and Halanaerobium praevalens were the predominant species in Sufu. Acetic acid and sucrose were found to be the primary major physicochemical factor influencing the bacterial communities in Dajiang and Sufu, respectively. Furthermore, Bacillus subtilis is strongly correlated with lactic acid levels, L. acidipiscis is positively correlated with acetic acid levels, while Staphylococcus sciuri and S. equorum are strongly, and positively, correlated with malic acid. Following analysis of carbohydrate and amino acid metabolism in all samples, cysteine and methionine metabolism, as well as fatty acid biosynthesis-related genes are upregulated in Dajiang compared to Sufu samples. However, such as the Staphylococcus , W. viridescens , and P. brenneri , as potentially foodborne pathogens, existed in Dajang and Sufu samples. Cumulatively, these results suggested that Dajiang and Sufu have unique bacterial communities that influence their specific characteristics. Hence, the current study provides insights into the microbial community composition in Dajiang and Sufu samples, which may facilitate the isolation of functional bacterial species suitable for Dajiang and Sufu production, thus improving their production efficiency. [ABSTRACT FROM AUTHOR]

Sufu is a type of fermented food with abundant nutrients and delicious taste. It is made from the fermentation of tofu by various microorganisms. In this study, three types of sufu were prepared through natural fermentation: (NF), single‐strain fermentation (SF), and mixed‐strain fermentation (MF). Microbial species, amino acids, and fatty acids were identified to investigate dynamic changes in nutritional quality and microbial flora in sufu. The results showed that the number of microbial species in NF sufu was the highest (n = 284), whereas that in SF sufu was the lowest (n = 194). Overall, 153 microbial species were found in all three types of sufu. Relative abundance analysis also revealed that Tetragonococcus, Bacillus, Acinetobacter, and Staphylococcus were the main bacteria in sufu. However, there was a large number of harmful bacteria such as Enterococcaceae in NF sufu. The levels of various nutrients were low in SF sufu, whereas the contents of protein and soy isoflavones were higher in NF and MF sufu. Seventeen kinds of amino acids were detected, comprising seven essential amino acids and ten other amino acids. The contents of essential amino acids and essential fatty acids were higher in MF sufu than the other two types, resulting in its high nutritional value. The sufu produced through the three fermentation methods differed significantly (p <.05) in terms of microbial flora and nutritional quality. [ABSTRACT FROM AUTHOR]

Centrosome duplication and DNA replication are two pivotal events that higher eukaryotic cells use to initiate proliferation. While DNA replication is initiated through origin licensing, centrosome duplication starts with cartwheel assembly and is partly controlled by CP110. However, the upstream coordinator for both events has been, until now, a mystery. Here, we report that suppressor of fused protein (Sufu), a negative regulator of the Hedgehog (Hh) pathway playing a significant role in restricting the trafficking and function of glioma-related (Gli) proteins, acts as an upstream switch by facilitating CP110 phosphorylation by CDK2, promoting intranuclear Cdt1 degradation and excluding prereplication complex (pre-RC) components from chromosomes, independent of its canonical function in the Hh pathway. We found that Sufu localizes to both the centrosome and the nucleus and that knockout of Sufu induces abnormalities including centrosome amplification, increased nuclear size, multipolar spindle formation, and polyploidy. Serum stimulation promotes the elimination of Sufu from the centrosome by vesicle release at the ciliary tip and from the nucleus via protein degradation, which allows centrosome duplication and DNA replication to proceed. Collectively, this work reveals a mechanism through which Sufu negatively regulates the G1-S transition. [ABSTRACT FROM AUTHOR]