Context-dependent T-BOX transcription factor family: from biology to targeted therapy.

T-BOX factors belong to an evolutionarily conserved family of transcription factors. T-BOX factors not only play key roles in growth and development but are also involved in immunity, cancer initiation, and progression. Moreover, the same T-BOX molecule exhibits different or even opposite effects in various developmental processes and tumor microenvironments. Understanding the multiple roles of context-dependent T-BOX factors in malignancies is vital for uncovering the potential of T-BOX-targeted cancer therapy. We summarize the physiological roles of T-BOX factors in different developmental processes and their pathological roles observed when their expression is dysregulated. We also discuss their regulatory roles in tumor immune microenvironment (TIME) and the newly arising questions that remain unresolved. This review will help in systematically and comprehensively understanding the vital role of the T-BOX transcription factor family in tumor physiology, pathology, and immunity. The intention is to provide valuable information to support the development of T-BOX-targeted therapy.

Multi-gene phylogenetic analyses revealed two novel species and one new record of Trichobotrys (Pleosporales, Dictyosporiaceae) from China.

The rotting wood in freshwater is a unique eco-environment favoring various fungi. During our investigation of freshwater fungi on decaying wood, three hyphomycetes were collected from Jiangxi and Guangxi Provinces, China. Based on the morphological observations and phylogenetic analysis of a combined DNA data containing ITS, LSU, SSU and tef1-α sequences, two new Trichobotrys species, T.meilingensis and T.yunjushanensis, as well as a new record of T.effusa, were introduced. Additionally, a comprehensive description of the genus with both morphological and molecular data was first provided.

An overview of Melanommataceae (Pleosporales, Dothideomycetes): Current insight into the host associations and geographical distribution with some interesting novel additions from plant litter.

Melanommataceous species exhibit high diversity with a cosmopolitan distribution worldwide and show a prominent saprobic lifestyle. In this study, we explored five saprobic species collected from plant litter substrates from terrestrial habitats in China and Thailand. A combination of morphological characteristics and multi-locus phylogenetic analyses was used to determine their taxonomic classifications. Maximum Likelihood and Bayesian Inference analyses of combined LSU, SSU, ITS and tef1-α sequence data were used to clarify the phylogenetic affinities of the species. Byssosphaeriapoaceicola and Herpotrichiazingiberacearum are introduced as new species, while three new host records, Bertiellafici, By.siamensis and Melanommapopulicola are also reported from litter of Cinnamomumverum, Citrustrifoliata and Fagussylvatica, respectively. Yet, despite the rising interest in the melanommataceous species, there is a considerable gap in knowledge on their host associations and geographical distributions. Consequently, we compiled the host-species associations and geographical distributions of all the so far known melanommataceous species.

Eccrine porocarcinoma in the tempus of an elderly woman: A case report.

BACKGROUND: Eccrine porocarcinoma (EPC) is a rare skin tumor that mainly affects the elderly population. Tumors often present with slow growth and a good prognosis. EPCs are usually distinguished from other skin tumors using histopathology and immunohistochemistry. However, surgical management alone may be inadequate if the tumor has metastasized. However, currently, surgical resection is the most commonly used treatment modality. CASE SUMMARY: A seventy-four-year-old woman presented with a slow-growing nodule in her left temporal area, with no obvious itching or pain, for more than four months. Histopathological examination showed small columnar and short spindle-shaped cells; thus, basal cell carcinoma was suspected. However, immunohistochemical analysis revealed the expression of cytokeratin 5/6, p63 protein, p16 protein, and Ki-67 antigen (40%), and EPC was taken into consideration. The skin biopsy was repeated, and hematoxylin and eosin staining revealed ductal differentiation in some cells. Finally, the patient was diagnosed with EPC, and Mohs micrographic surgery was performed. We adapted follow-up visits in a year and not found any recurrence of nodules. CONCLUSION: This case report emphasizes the diagnosis and differentiation of EPC.

Biphasic photobiomodulation of inflammation in mouse models of common wounds, infected wounds, and diabetic wounds.

Bidirectional photobiomodulation (PBM) therapy is an active research area. However, most studies have focused on its dependence on optical parameters rather than on its tissue-dependent effects. We constructed mouse models of wounds in three inflammatory states (normal, low, and high levels of inflammations) to assess the bidirectional regulatory effect of PBM on inflammation. Mice were divided into three groups to prepare common wounds, diabetic wounds, and bacteria-infected wounds. The same PBM protocol was used to regularly irradiate the wounds over a 14 d period. PBM promoted healing of all three kinds of wounds, but the inflammatory manifestations in each were significantly different. In common wounds, PBM slightly increased the aggregation of inflammatory cells and expression of IL-6 but had no effect on the inflammatory score. For wounds in a high level of inflammation caused by infection, PBM significantly increased TNF-α expression in the first 3 d of treatment but quickly eliminated inflammation after the acute phase. For the diabetic wounds in a low level of inflammation, PBM intervention significantly increased inflammation scores and prevented neutrophils from falling below baseline levels at the end of the 14 d observation period. Under fixed optical conditions, PBM has a bidirectional (pro- or anti-inflammatory) effect on inflammation, depending on the immune state of the target organism and the presence of inflammatory stimulants. Our results provide a basis for the formulation of clinical guidelines for PBM application.

Transcription factor BACH1 in cancer: roles, mechanisms, and prospects for targeted therapy.

Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status of BACH1 in malignant tumor behaviors, and summarize its role in immune regulation in cancer. Moreover, this review focuses on the potential of BACH1 as a novel therapeutic target and prognostic biomarker. Notably, the mechanisms underlying the roles of BACH1 in ferroptosis, oxidative stress and tumor microenvironment remain to be explored. BACH1 has a dual impact on cancer, which affects the accuracy and efficiency of targeted drug delivery. Finally, the promising directions of future BACH1 research are prospected. A systematical and clear understanding of BACH1 would undoubtedly take us one step closer to facilitating its translation from basic research into the clinic.

SOX on tumors, a comfort or a constraint?

The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family, composed of 20 transcription factors, is a conserved family with a highly homologous HMG domain. Due to their crucial role in determining cell fate, the dysregulation of SOX family members is closely associated with tumorigenesis, including tumor invasion, metastasis, proliferation, apoptosis, epithelial-mesenchymal transition, stemness and drug resistance. Despite considerable research to investigate the mechanisms and functions of the SOX family, confusion remains regarding aspects such as the role of the SOX family in tumor immune microenvironment (TIME) and contradictory impacts the SOX family exerts on tumors. This review summarizes the physiological function of the SOX family and their multiple roles in tumors, with a focus on the relationship between the SOX family and TIME, aiming to propose their potential role in cancer and promising methods for treatment.

Morphological and phylogenetic analyses reveal a new species of Anthracophyllum (Omphalotaceae, Agaricales) in Zhejiang Province, China.

During the investigations of macrofungi resources in Zhejiang Province, China, an interesting wood rot fungus was collected. Based on morphological and molecular phylogenetic studies, it is described as a new species, Anthracophyllum sinense. A. sinense is characterized by its sessile, charcoal black and pleurotoid pileus, sparse lamellae occasionally branching, clavate basidia with long sterigmata [(3-)6-7(-8) µm], and non-heteromorphous cystidia. A. sinense establishes a separate lineage close to A. archeri and A. lateritium in the phylogenetic tree.

SRSF10 facilitates HCC growth and metastasis by suppressing CD8+T cell infiltration and targeting SRSF10 enhances anti-PD-L1 therapy.

BACKGROUND AND AIMS: RNA splicing is an essential step in regulating the gene posttranscriptional expression. Serine/arginine-rich splicing factors (SRSFs) are splicing regulators with vital roles in various tumors. Nevertheless, the expression patterns and functions of SRSFs in hepatocellular carcinoma (HCC) are not fully understood. METHODS: Flow cytometry and immunofluorescent staining were used to determine the CD8+T cell infiltration. Orthotopic HCC model, lung metastasis model, DEN/CCl4 model, Srsf10△hep model, and Srsf10HepOE model were established to evaluate the role of SRSF10 in HCC and the efficacy of combination treatment. RESULTS: SRSF10 was one of the most survival-relevant genes among SRSF members and was an independent prognostic factor for HCC. SRSF10 facilitated HCC growth and metastasis by suppressing CD8+T cell infiltration. Mechanistically, SRSF10 down-regulated the p53 protein by preventing the exon 6 skipping (exon 7 in mouse) mediated degradation of MDM4 transcript, thus inhibiting CD8+T cell infiltration. Elimination of CD8+T cells or overexpression of MDM4 removed the inhibitory role of SRSF10 knockdown in HCC growth and metastasis. SRSF10 also inhibited the IFNα/γ signaling pathway and promoted the HIF1α-mediated up-regulation of PD-L1 in HCC. Hepatocyte-specific SRSF10 deficiency alleviated the DEN/CCl4-induced HCC progression and metastasis, whereas hepatocyte-specific SRSF10 overexpression deteriorated these effects. Finally, SRSF10 knockdown enhanced the anti-PD-L1-mediated anti-tumor activity. CONCLUSIONS: SRSF10 promoted HCC growth and metastasis by repressing CD8+T cell infiltration mediated by the MDM4-p53 axis. Furthermore, SRSF10 suppressed the IFNα/γ signaling pathway and induced the HIF1α signal mediated PD-L1 up-regulation. Targeting SRSF10 combined with anti-PD-L1 therapy showed promising efficacy.

Phylogenetic and Morphological Evidence Reveal Five New Species of Boletes from Southern China.

Fungi of the order Boletales are extremely important in both ecology and economy, since most of them are ectomycorrhizal fungi, which play vital roles in maintaining forest ecosystems, water and soil protection, vegetation restoration and so on. Although previous studies have shown that this order has a very high species diversity in China, there are few reports on the species diversity of boletes in Jiangxi Province, China. Based on morphological (macroscopic and microscopic morphological characteristics) and phylogenetic analyses (ITS, LSU, and TEF1-α sequences), in this study, the wild boletes in Jiangxi Province were investigated, and five new species are described: Austroboletus albus, Xanthoconium violaceipes, Xanthoconium violaceofuscum, Xerocomus rutilans and Xerocomus subsplendidus. Descriptions and hand drawings of the new species are presented.

Functional Components from the Liquid Fermentation of Edible and Medicinal Fungi and Their Food Applications in China.

Functional raw materials rich in various effective nutrients and active ingredients that are of stable quality can be obtained from the liquid fermentation of edible and medicinal fungi. In this review, we systematically summarize the main findings of this comparative study that compared the components and efficacy of liquid fermented products from edible and medicinal fungi with those from cultivated fruiting bodies. Additionally, we present the methods used in the study to obtain and analyze the liquid fermented products. The application of these liquid fermented products in the food industry is also discussed. With the potential breakthrough of liquid fermentation technology and the continued development of these products, our findings can serve as a reference for further utilization of liquid fermented products derived from edible and medicinal fungi. Further exploration of liquid fermentation technology is necessary to optimize the production of functional components from edible and medicinal fungi, and to enhance their bioactivity and safety. Investigation of the potential synergistic effects of combining liquid fermented products with other food ingredients is also necessary to enhance their nutritional values and health benefits.

KMT2E Haploinsufficiency Manifests Autism-Like Behaviors and Amygdala Neuronal Development Dysfunction in Mice.

Autism spectrum disorders (ASD) are highly heterogeneous neurodevelopmental disorders characterized by impaired social interaction skills. Whole exome sequencing has identified loss-of-function mutations in lysine methyltransferase 2E (KMT2E, also named MLL5) in ASD patients and it is listed as an ASD high-risk gene in humans. However, experimental evidence of KMT2E in association with ASD-like manifestations or neuronal function is still missing. Relying on KMT2E+/- mice, through animal behavior analyses, positron emission tomography (PET) imaging, and neuronal morphological analyses, we explored the role of KMT2E haploinsufficiency in ASD-like symptoms. Behavioral results revealed that KMT2E haploinsufficiency was sufficient to produce social deficit, accompanied by anxiety in mice. Whole-brain 18F-FDG-PET analysis identified that relative amygdala glycometabolism was selectively decreased in KMT2E+/- mice compared to wild-type mice. The numbers and soma sizes of amygdala neurons in KMT2E+/- mice were prominently increased. Additionally, KMT2E mRNA levels in human amygdala were significantly decreased after birth during brain development. Our findings support a causative role of KMT2E in ASD development and suggest that amygdala neuronal development abnormality is likely a major underlying mechanism.

A new species of Dictyochaeta (Sordariomycetes, Chaetosphaeriales, Chaetosphaeriaceae) from freshwater habitats in China.

Background: Freshwater fungi refer to the fungi that depend on the freshwater habitats for the whole life cycle or part of their life cycle. In this context, a new aquatic hyphomycete was isolated from decaying wood in a freshwater habitat in Jiangxi Province, China. New information: Dictyochaetajiangxiensis sp. nov., a new aquatic hyphomycete, is characterised by its unbranched, septate, base-fertile conidiophores with multisepta and single phialide at the apex, brown, sterile seta, monophialidic, subcylindrical conidiogenous cells narrowing below the funnel-shaped collarette, hyaline, unicellular, thin-walled, smooth, guttulate, falcate to subclavate conidia narrowly rounded at both ends with hair-like appendages. Phylogenetically, the new species Dictyochaetajiangxiensis clustered together with Dictyochaetabrevis MFLU 19-0216 in a well-supported clade, but formed a separate branch. In order to better define the taxonomic status of the new species, a phylogenetic tree of most closely-related taxa in Chaetosphaeriaceae was established, based on multi-locus sequences (ITS and LSU). The novel species is described and illustrated. Newly-generated molecular data of Dictyochaetajiangxiensis is also provided.

Three novel species of Distoseptispora (Distoseptisporaceae) isolated from bamboo in Jiangxi Province, China.

Decaying bamboo in freshwater is a unique eco-environment for fungi. Three new Distoseptispora (Distoseptisporaceae) species, D.meilingensis, D.yongxiuensis and D.yunjushanensis from submerged decaying bamboo culms in Jiangxi Province, China, were discovered, based on phylogenetic analyses and morphological characters. The combined data of ITS-LSU-SSU-Tef1 sequences were used to infer the phylogenetic relationship between D.meilingensis, D.yongxiuensis, D.yunjushanensis and related species. Both molecular analyses and morphological data supported D.meilingensis, D.yongxiuensis and D.yunjushanensis as three independent taxa.

Analysis of genetic diversity among Chinese Cyclocybe chaxingu strains using ISSR and SRAP markers.

Background: Cyclocybe chaxingu is an edible and medicinal fungal species commonly cultivated in China. The major problems currently facing by growers of C. chaxingu is the random labeling of strains and strains aging and degeneration. Therefore, an evaluation of genetic diversity is essential for the conservation and reproducing programs of this species. Methods: In the present study, 24 widely cultivated strains were collected from the main producing areas of China, and the genetic diversity analysis was performed. DNA polymorphism among these Chinese C. chaxingu strains was analyzed using inter-simple sequence repeat (ISSR) and sequence-related amplified polymorphism (SRAP) markers. Results: Eight ISSR primers amplified a total of 75 DNA fragments of which 61 (81.33%) were polymorphic. Fifteen SRAP primer combinations amplified 166 fragments of which 132 (79.52%) were polymorphic. Cluster analysis showed that the C. chaxnigu strains fall into five groups with a genetic distance values ranging from 0.06 to 0.60 by ISSR analysis, while the SRAP analysis divided the test strains into four groups within the range of genetic distance from 0.03 to 0.57. The results of the present study reveal a high level of genetic diversity among the widely cultivated C. chaxingu strains.

Immunotherapy for type 1 diabetes mellitus by adjuvant-free Schistosoma japonicum-egg tip-loaded asymmetric microneedle patch (STAMP).

BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disease mediated by autoreactive T cells and dominated by Th1 response polarization. Insulin replacement therapy faces great challenges to this autoimmune disease, requiring highly frequent daily administration. Intriguingly, the progression of T1DM has proven to be prevented or attenuated by helminth infection or worm antigens for a relatively long term. However, the inevitable problems of low safety and poor compliance arise from infection with live worms or direct injection of antigens. Microneedles would be a promising candidate for local delivery of intact antigens, thus providing an opportunity for the clinical immunotherapy of parasitic products. METHODS: We developed a Schistosoma japonicum-egg tip-loaded asymmetric microneedle patch (STAMP) system, which serves as a new strategy to combat TIDM. In order to improve retention time and reduce contamination risk, a specific imperfection was introduced on the STAMP (asymmetric structure), which allows the tip to quickly separate from the base layer, improving reaction time and patient's comfort. After loading Schistosoma japonicum-egg as the immune regulator, the effects of STAMP on blood glucose control and pancreatic pathological progression improvement were evaluated in vivo. Meanwhile, the immunoregulatory mechanism and biosafety of STAMP were confirmed by histopathology, qRT-PCR, ELISA and Flow cytometric analysis. RESULTS: Here, the newly developed STAMP was able to significantly reduce blood glucose and attenuate the pancreatic injury in T1DM mice independent of the adjuvants. The isolated Schistosoma japonicum-eggs micron slowly degraded in the skin and continuously released egg antigen for at least 2 weeks, ensuring localization and safety of antigen stimulation. This phenomenon should be attributed to the shift of Th2 immune response to reduce Th1 polarization. CONCLUSION: Our results exhibited that STAMP could significantly regulate the blood glucose level and attenuate pancreatic pathological injury in T1DM mice by balancing the Th1/Th2 immune responses, which is independent of adjuvants. This technology opens a new window for the application of parasite products in clinical immunotherapy.

Aquapteridospora jiangxiensis, a new aquatic hyphomycetous fungus from a freshwater habitat in China.

During an investigation of freshwater fungi in Jiangxi province, China, a new hyphomycetous fungus, Aquapteridospora jiangxiensis, was collected and isolated. Aquapteridospora jiangxiensis is characterized by its unbranched and guttulate conidiophores with multi-septa swollen at the base, polyblastic conidiogenous cells with sympodial proliferations, and denticles, and guttulate conidia with a sheath. A photo plate of the macro- and micro-morphology and a muti-loci (ITS, LSU, SSU, TEF1 and RPB2) phylogenetic tree are provided. A key to the species of Aquapteridospora is also presented in this paper.

Retiboletus atrofuscus (Boletaceae, Boletales), a new species from China.

Based on morphological and phylogenetic analyses, an ectomycorrhizal fungus collected from Jiangxi, China, is described as a new species. R. atrofuscus is morphological characterized by a dark gray to black pileus, white to pale yellowish white hymenophore, a grayish brown to pale yellow context, which turning orange-yellow to rusty yellow when injured, a prominently and coarsely white to pale yellow to black reticulation on upper 3/4 or entire stipe, grayish yellow to pale yellow to yellowish brown basidiospores in KOH with measuring (7-)7.5-13(-13.5) × (3-)3.5-5(-5.5) µm. Phylogenetic analysis results showed that R. atrofuscus formed an independent lineage within Retiboletus. Descriptions and hand drawings of the new species and comparisons with similar species are presented.

Phaeoisarialaianensis (Pleurotheciales, Pleurotheciaceae), a new species from freshwater habitats in China.

Background: Freshwater fungi play an indispensable role in the ecosystem and have great research value. Based on morphological and phylogenetic analyses of a concatenated dataset of ITS, LSU and SSU sequences, a new species, Phaeoisarialaianensis, was introduced as a freshwater hyphomycete from Anhui Province, China. New information: Phaeoisarialaianensis was morphologically described as erect, rigid, dark brown to black, velvety synnemata which has macronematous, septate, branched, brown to dark brown, parallel adpressed conidiophores with polyblastic, integrated, terminal, hyaline to pale brown, smooth, denticulate, sympodial conidiogenous cells and ellipsoidal to obovoid, rounded at the apex, obtuse and tapering towards base, septate, guttulate conidia. Based on molecular and morphological characteristics, it is confirmed to be a new species. All illustrations and descriptions have been provided.

Menisporopsisaquatica sp. nov. (Sordariomycetes, Chaetosphaeriales, Chaetosphaeriaceae), from freshwater habitat in China.

Background: Freshwater fungi are an integral part of freshwater ecosystems. They promote the carbon cycle of the ecosystem by decomposing wood substrates. Menisporopsis is a fungal genus of Chaetosphaeriales in Sordariomycetes, which has been commonly collected from aquatic and marine environments. Most species of this genus are saprophytes. New information: Here, a new freshwater hyphomycetous fungus, Menisporopsisaquatica, reported from submerged rotten wood samples collected in a stream in Zhejiang Province, south-eastern China. The new species is characterised by hyaline conidia appendiculate with 1-2 setulae at each end and synnematous conidiophores growing closely around a black central seta. Molecular phylogeny of Menisporopsis was studied using a combined two-loci dataset, including the internal transcribed spacer sequences (ITS) and the nuclear ribosomal large subunit gene sequences (nrLSU). The new species is illustrated and a synopsis of the Menisporopsis species is presented in this paper.