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Abstract Background To compare the value and efficiency of the three-dimensional (3D) heads-up surgical system and traditional microscopic (TM) system in teaching and learning vitreoretinal surgeries. Methods Twenty ophthalmologists and scrub nurses were recruited as teachers, and 45 junior ophthalmology residents and trainee doctors, trainee nurses, and medical students were recruited as observers. Each teacher and observer were assigned to both a 3D-assisted and TM-assisted vitreoretinal surgery and then asked to complete satisfaction questionnaires for both surgical systems at the end of each surgery. Results The 3D heads-up surgical system was rated significantly higher in most of the subscales and overall satisfaction score by both teachers and observers (P

Abstract Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions.

Ralstonia solanacearum causes a lethal bacterial wilt disease in many crops, leading to huge losses in crop production every year. Understanding of plant–R. solanacearum interactions will aid to develop efficient strategies to control the disease. As a soilborne pathogen, R. solanacearum naturally infects plants via roots. A huge limitation in studying plant–R. solanacearum interactions is the large variation of R. solanacearum infection assay due to the variable soil conditions and uneven inoculum exposure. Here, we developed a robust and reliable Petri-dish inoculation method which allows consistent and stable infection in young plant seedlings. This method is easy to use, takes about only 10 days from seed germination to the completion of inoculation assay, and requires less inoculum of bacteria as well as growth chamber space. We proved the efficacy of the seedling Petri-dish inoculation method by analyzing plant defense primed by molecular patterns, resistance of defense-related plant mutants, and virulence of R. solanacearum mutants. Furthermore, we demonstrated that the seedling Petri-dish inoculation method can be applied to other host plants such as tobacco and has great potential for high-throughput screening of resistant plant germplasms to bacterial wilt in the future.

Invasion success of clonal plants is closely related to their unique clonal life history, and clonal division of labor is a crucial clonal trait. However, so far, it is unclear whether invasive alien clonal species generally possess a greater capacity for division of labor than native species and whether this pattern is affected by environmental conditions. To test whether patch contrast affects the differences in the capacity for division of labor between invasive alien and native clonal plants, we selected five pairs of exotic invasive and native clonal plant species that are congeneric and co-occurring in China as experimental materials. We grew the clonal fragment pairs of these invasive and native plants under high, low, or no contrast of reciprocal patchiness of light and nutrient, respectively, with ramet connections either severed (division of labor prevented) or kept intact (division of labor allowed). The results showed that connection significantly decreased the proportion of biomass allocated to roots in distal (younger) ramets, whereas it increased in proximal (older) ramets of all studied plants under high -contrast treatments. This clear pattern strongly indicated the occurrence of division of labor. Furthermore, the connection had a more pronounced effect on the pattern of biomass allocation of invasive alien plants, resulting in a greater increase in biomass for invasive alien plants compared to native plants. These findings suggest that the invasive alien plants possess a greater capacity for division of labor, which may confer a competitive advantage to them over natives, thus facilitating their invasion success in some heterogeneous habitats such as forest edges where light and soil nutrients show a high negative correlation.

BackgroundCytomegalovirus retinitis (CMVR) is the most common and sight-threatening opportunistic retinal infection in patients with acquired immunodeficiency syndrome (AIDS) and several controversies remain to be settled. We aimed to summarize the current evidence and clarify the clinical features and prognosis of CMVR in AIDS patients.MethodsThe databases PubMed, EMBASE, and Ovid from inception to April 2022 were searched to identify the relevant studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval (CI) were calculated using the Freeman-Tukey variant of arcsine square transformation.ResultsWe finally included 236 studies comprising 20,214 patients. CMVR in AIDS was male-dominated (88%, 95%CI 86%-89%), with 57% (95%CI 55%-60%) aged

Abstract Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.

Abstract The objective of this study was to predict the value of lymphocyte subsets in cancer progression. Peripheral blood was obtained from 327 untreated patients with cancer and 158 healthy volunteers. Levels of lymphocyte subsets were determined by flow cytometry. There were decreased levels of natural killer (NK) cells, CD8+ T cells, and naïve CD4+/CD4+ T cells in untreated patients with cancer compared to those in healthy controls. Inversely, there were elevated levels of the following T‐cell percentages in cancer patients compared to those in healthy controls: memory CD4+/CD4+, CD8+ T cells, HLA‐DR/CD8+, CD8+ CD38+/CD8+, and CD4+/CD8+. In addition, there are a decreasing trend in terms of CD4+ T‐cell counts and an increase CD8+ HLA‐DR/CD8+ T‐cell and CD8+ CD38+/CD8+ T‐cell percentages in the advanced stage. An increasing trend with advanced tumor stage and the percentages of CD8+ HLA‐DR/CD8+ T cells and CD8+ CD38+/CD8+ T cells was shown in this study. There are a negative correlation for CD4+ T‐cell counts and positive correlation for percentages of CD8+ HLA‐DR/CD8+ T cell and CD8+ CD38+/CD8+ T cells with the lymph node metastasis. In the presence of distant metastatic spread, we observed higher NK‐cell counts, CD8+ HLA‐DR/CD8+ T‐cell percentages, CD8+ CD38+/CD8+ T‐cell percentages, as well as lower CD4+ T‐cell counts than those in the absence of distant metastases spread. Abnormal levels of NK cell, CD8+ T cells, memory CD4+/CD4+, naïve CD4+/ CD4+, CD8+ HLA‐DR/CD8+, CD8+ CD38+/CD8+, and CD4+/CD8+ can be a potential blood biomarkers of cancer development. CD4+ T‐cell counts and percentages of CD8+ HLA‐DR/ CD8+ and CD8+ CD38+/ CD8+ can predict the cancer progression.

Background: Patients with chronic schizophrenia present cognitive impairment, which affects their social function and prevents them from reintegrating into society. Yijinjing is a traditional Chinese aerobic exercise that has a putative psychosomatic effect on improving cognitive function.Methods: From January to May 2021, 40 patients with chronic schizophrenia were recruited and randomly divided into a control group and a Yijinjing group. In the 12-week intervention, the patients in the control group received conventional treatment, whereas patients in the Yijinjing group performed Yijinjing exercise (40 min/session, twice a week) in addition to receiving conventional treatment. The Positive and Negative Syndrome Scale (PANSS), the Insight and Treatment Attitude Questionnaire (ITAQ), the Rosenberg Self-esteem Scale (SES), and the Mini Mental State Examination (MMSE) were used to measure clinical symptoms and cognitive function at 0, 6, and 12 weeks.Results: The demographic information was not significantly different between groups. At baseline, the scores of all the scales were not statistically different between groups. After 12 weeks of intervention, compared to those at baseline, the scores of the negative scale (t = 19.00, p < 0.0001), general psychopathology scale (t = 15.98, p < 0.0001), and total score (t = 15.47, p < 0.0001) of the PANSS and SES (t = 5.378, p < 0.0001) had significantly decreased, and the scores of the ITAQ (t = 7.984, p < 0.0001) and MMSE (t = 6.750, p < 0.0001) had significantly increased in Yijinjing group; the score of the MMSE increased in the control group as well (t = 2.491, p = 0.0222). Compared to the respective scores in the control group, the negative scale score (t = 2.953, p = 0.0054) significantly decreased, and the ITAQ (t = 3.043, p = 0.0042) and MMSE (t = 2.2.68, p = 0.0291) scores significantly increased in the Yijinjing group after 12 weeks of intervention.Conclusion: These results provide a preliminary indication that Yijinjing exercise had the potential to improve cognitive function and negative symptoms in patients with chronic schizophrenia. A larger-scale study to determine the trajectory of change in the longer term should be undertaken.

Abstract Human microbiomes, considered as a new emerging and enabling cancer hallmark, are increasingly recognized as critical effectors in cancer development and progression. Manipulation of microbiome revitalizing anticancer therapy from natural products shows promise toward improving cancer outcomes. Herein, we summarize our current understanding of the human microbiome‐driven molecular mechanisms impacting cancer progression and anticancer therapy. We highlight the potential translational and clinical implications of natural products for cancer prevention and treatment by developing targeted therapeutic strategies as adjuvants for chemotherapy and immunotherapy against tumorigenesis. The challenges and opportunities for future investigations using modulation of the microbiome for cancer treatment are further discussed in this review.

Abstract Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74 000 human single cells were profiled. As results, we found that SPP1+ macrophages, RGCC+ endothelial cells, ACKR1+ endothelial cells and ADAM12+ fibroblasts participated in tendon adhesion formation. Interestingly, despite specific fibrotic clusters in tendon adhesion, FOLR2+ macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells. Furthermore, ACKR1 was verified to regulate FOLR2+ macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R tdTomato mice to lethally irradiated Ackr1 −/− mice (Ackr1 −/− chimeras; deficient in ACKR1) and control mice (WT chimeras). Compared with WT chimeras, the decline of FOLR2+ macrophages was also observed, indicating that ACKR1 was specifically involved in FOLR2+ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered a novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.

Abstract Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

Abstract The human microbiome exhibits a profound connection with the cancer development, progression, and therapeutic response, with particular emphasis on its components of the mycobiome, which are still in the early stages of research. In this review, we comprehensively summarize cancer‐related symbiotic and pathogenic fungal genera. The intricate mechanisms through which fungi impact cancer as an integral member of both gut and tissue‐resident microbiomes are further discussed. In addition, we shed light on the pivotal physiological roles of various nutrients, including cholesterol, carbohydrates, proteins and minerals, in facilitating the growth, reproduction, and invasive pathogenesis of the fungi. While our exploration of the interplay between nutrients and cancer, mediated by the mycobiome, is ongoing, the current findings have yet to yield conclusive results. Thus, delving into the relationship between nutrients and fungal pathogenesis in cancer development and progression would provide valuable insights into anticancer therapy and foster precision nutrition and individualized treatments that target fungi from bench to bedside.

Abstract Background Cancer, a global threat to human health, refers to a large crowd of lethal diseases that can start in almost all tissues or organs of our body when abnormal cells grow uncontrollably and beyond their usual boundaries, followed by invading adjacent normal tissues and spreading to distant organs. Recently, substantial evidence has demonstrated polymorphic microbiome as an emerging cancer characteristic present in a variety of tumour types. By releasing metabolites or other signalling molecules, microbiota can affect immune cell differentiation and activity, including both innate and adaptive immunological responses, as well as the growth and multiplication of cancer cells. It was now employed as a biomarker to predict the patients’ survival rate and the degree of cancer progression. Main To investigate the underlying mechanism and the technology development of how polymorphic microbiome influence the tumour microenvironment and subsequently cancer progression, we have carried out systematic literature review about polymorphic microbiome and tumour development from bulk to single‐cell level. Conclusions Here, we provide an overview of the current advancements of host–microbiota interactions during cancer progression from bulk to single‐cell level and discuss the challenges and opportunities in future, looking forward to ascertain the specific activity of different somatic cell types with or without the existence of various multi‐kingdom microbiota and their by‐products and supply a holistic and elaborate investigation of host‐microbiota interaction in the development of cancer.

Abstract Colorectal cancer (CRC) is a multistage and highly heterogeneous malignant disease that mostly occurred in aged people accompanied by microbiota alteration. Emerging evidence has uncovered the role of bacterial microbiota in the initiation and development of CRC. However, the effects of nonbacterial members inhabiting the human body, such as fungi, archaea, and viruses, have been largely ignored. The multi‐kingdom microbiota can be altered by dietary exposures and probiotic supplements. Furthermore, the efficacy of antitumor therapeutic strategies, such as radiotherapy, chemotherapy, and immunotherapy, are also closely associated with the alteration of multi‐kingdom microbiota. In this review, we describe CRC‐associated multi‐kingdom microbiota dysbiosis and the role of daily diet on CRC progression through microbiota alteration. We then discuss the impact of microbiota in different CRC therapies and highlight the advances as well as challenges in understanding how multi‐kingdom microbiome impacts the outcome of CRC.

Abstract Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant inherited disease caused by mutations in genes encoding cardiac sarcomere proteins. MicroRNAs (miRNAs) play an important role in the pathogenesis of FHCM. In the present study, we aimed to determine the miRNA profile in FHCM patients with myosin-binding protein C3 (MYBPC3) gene mutations. We recruited three FHCM patients and age- and sex-matched controls. The three probands all had hypertrophic obstructive cardiomyopathy with severe myocardial hypertrophy, and two of the three had a history of sudden cardiac death, representing a “malignant” phenotype. We then compared the miRNA expression profiles of three FHCM patients carrying MYBPC3 gene mutations with those of the normal control group using miRNA sequencing technology. Differentially expressed miRNAs were verified using real-time polymerase chain reaction (qPCR). Target genes and signaling pathways of the identified differentially expressed miRNAs were predicted using bioinformatics analysis. A total of 33 significantly differentially expressed miRNAs were detected in the peripheral blood of the three probands, of which 28 were upregulated, including miR-208b-3p, and 5 were downregulated. Real-time PCR confirmed the upregulated expression of miR-208b-3p in FHCM patients (P

AIM: To assess efficacy of intravitreal conbercept (IVC) injection in combination with panretinal photocoagulation (PRP) vs PRP alone in patients with severe nonproliferative diabetic retinopathy (SNPDR) without macular edema (ME). METHODS: Forty-eight patients with SNPDR without ME (56 eyes) were divided into the PRP group and IVC+PRP group (the pulse group) in this retrospective clinical study. Conbercept was intravitreally administered to patients in the pulse group 1wk before treatment with PRP and followed up for 1, 3, and 6mo. The best-corrected visual acuity (BCVA, logMAR), center foveal thickness (CFT), visual acuity (VA) improvement, and adverse reactions were compared between groups. RESULTS: In the PRP group, the BCVA reduced at 1 and 3mo before improving at 6mo. In the pulse group, baseline BCVA decreased continuously at 1mo, increased at 3 and 6mo. BCVA in the pulse group was better than that in the PRP group at 1, 3, and 6mo. There was an increase in CFT in the PRP group during follow-up compared with baseline. In the pulse group, CFT was increased at 1mo relative to baseline, steadily decreased to the baseline level at 3 and 6mo. There was a more significant reduction in CFT in the pulse group during follow-up compared with the PRP group. The effective rates of VA in the PRP and the pulse groups were 81.48% and 100%, respectively. CONCLUSION: As PRP pretreatment, a single dose of IVC administration has beneficial effects for preventing PRP-induced foveal thickening and increasing VA in patients with SNPDR without ME.

Colorectal cancer (CRC) is one of the most prevalent and life-threatening cancer types with limited therapeutic options worldwide. Gut microbiota has been recognized as the pivotal determinant in maintaining gastrointestinal (GI) tract homeostasis, while dysbiosis of gut microbiota contributes to CRC development. Recently, the beneficial role of postbiotics, a new concept in describing microorganism derived substances, in CRC has been uncovered by various studies. However, a comprehensive characterization of the molecular identity, mechanism of action, or routes of administration of postbiotics, particularly their role in CRC, is still lacking. In this review, we outline the current state of research toward the beneficial effects of gut microbiota derived postbiotics against CRC, which will represent the key elements of future precision-medicine approaches in the development of novel therapeutic strategies targeting gut microbiota to improve treatment outcomes in CRC.

Summary Fungal infections have emerged as a major global threat to human health because of the increasing incidence and mortality rates every year. The emergence of drug resistance and limited arsenal of antifungal agents further aggravates the current situation resulting in a growing challenge in medical mycology. Here, we identified that ponatinib, an FDA‐approved antitumour drug, significantly enhanced the activity of the azole fluconazole, the most widely used antifungal drug. Further detailed investigation of ponatinib revealed that its combination with fluconazole displayed broad‐spectrum synergistic interactions against a variety of human fungal pathogens such as Candida albicans, Saccharomyces cerevisiae and Cryptococcus neoformans. Mechanistic insights into the mode of action unravelled that ponatinib reduced the efflux of fluconazole via Pdr5 and suppressed the expression of the proton pump, Pma1. Taken together, our study identifies ponatinib as a novel antifungal that enhances drug activity of fluconazole against diverse fungal pathogens.

Abstract Background Oral cancer is a malignant disease that threatenshuman life and greatly reducespatientquality of life. ANLN was reported to promote the progression of cancer. This study aims to investigate the role of ANLNin oral cancer and the underlying molecular mechanism. Methods ANLN expression was downregulated by RNAi technology. The effect of ANLN on cell behaviors, including proliferation, cell cycle progression, invasion, and apoptosis, was detected. Western blotting analysis was used to explore the mechanism by whichANLN functions in oral cancer. Results Data from TCGA database showed that ANLN was expressed at significantly higher levels in tumor tissues thanin normal control tissues. Patients with higher ANLN expression exhibitedshorter survivaltimes. ANLN was alsoabundantly expressedin the cancer cell lines CAL27 and HN30. When ANLN was knocked down in CAL27 and HN30 cells, cell proliferation and colony formation weredecreased. The cell invasion ability was also inhibited. However, the cell apoptosis rate was increased. In addition, the levels of critical members of the PI3K signaling pathway, includingPI3K, mTOR, Akt, and PDK-1, were significantlyreducedafter ANLN was knocked down in CAL27 cells. Conclusions ANLN contributes to oral cancerprogressionand affects activation ofthe PI3K/mTOR signaling pathway. This study providesa new potential targetfor drug development and treatment in oral cancer.

Abstract Associations between gut microbiota and colorectal cancer (CRC) have been widely investigated. However, the replicable markers for early-stage adenoma diagnosis across multiple populations remain elusive. Here, we perform an integrated analysis on 1056 public fecal samples, to identify adenoma-associated microbial markers for early detection of CRC. After adjusting for potential confounders, Random Forest classifiers are constructed with 11 markers to discriminate adenoma from control (area under the ROC curve (AUC) = 0.80), and 26 markers to discriminate adenoma from CRC (AUC = 0.89), respectively. Moreover, we validate the classifiers in two independent cohorts achieving AUCs of 0.78 and 0.84, respectively. Functional analysis reveals that the altered microbiome is characterized with increased ADP-l-glycero-beta-d-manno-heptose biosynthesis in adenoma and elevated menaquinone-10 biosynthesis in CRC. These findings are validated in a newly-collected cohort of 43 samples using quantitative real-time PCR. This work proves the validity of adenoma-specific markers across multi-populations, which would contribute to the early diagnosis and treatment of CRC.

Whether to commit limited cellular resources toward growth and proliferation, or toward survival and stress responses, is an essential determination made by Target of Rapamycin Complex 1 (TORC1) for a eukaryotic cell in response to favorable or adverse conditions. Loss of TORC1 function is lethal. The TORC1 inhibitor rapamycin that targets the highly conserved Tor kinase domain kills fungal pathogens like Candida albicans, but is also severely toxic to human cells. The least conserved region of fungal and human Tor kinases are the N-terminal HEAT domains. We examined the role of the 8 most N-terminal HEAT repeats of C. albicans Tor1. We compared nutritional- and stress responses of cells that express a message for N-terminally truncated Tor1 from repressible tetO, with cells expressing wild type TOR1 from tetO or from the native promoter. Some but not all stress responses were significantly impaired by loss of Tor1 N-terminal HEAT repeats, including those to oxidative-, cell wall-, and heat stress; in contrast, plasma membrane stress and antifungal agents that disrupt plasma membrane function were tolerated by cells lacking this Tor1 region. Translation was inappropriately upregulated during oxidative stress in cells lacking N-terminal Tor1 HEAT repeats despite simultaneously elevated Gcn2 activity, while activation of the oxidative stress response MAP kinase Hog1 was weak. Conversely, these cells were unable to take advantage of favorable nutritional conditions by accelerating their growth. Consuming oxygen more slowly than cells containing wild type TOR1 alleles during growth in glucose, cells lacking N-terminal Tor1 HEAT repeats additionally were incapable of utilizing non-fermentable carbon sources. They were also hypersensitive to inhibitors of specific complexes within the respiratory electron transport chain, suggesting that inefficient ATP generation and a resulting dearth of nucleotide sugar building blocks for cell wall polysaccharides causes cell wall integrity defects in these mutants. Genome-wide expression analysis of cells lacking N-terminal HEAT repeats showed dysregulation of carbon metabolism, cell wall biosynthetic enzymes, translational machinery biosynthesis, oxidative stress responses, and hyphal- as well as white-opaque cell type-associated genes. Targeting fungal-specific Tor1 N-terminal HEAT repeats with small molecules might selectively abrogate fungal viability, especially when during infection multiple stresses are imposed by the host immune system.

Fungal infection poses a severe threat to human health worldwide resulting in a serious problem in clinic. Due to the limited arsenal of existing antifungal drugs, the nanomaterials were thus regarded as the candidate for developing new antifungal drugs. On the one hand, the antifungal nanomaterials are divided into inorganic nanomaterials, organic nanomaterials, and hybrid nanomaterials, among which inorganic nanoparticles include metal and semiconducting categories. On the other hand, they can also be divided into inorganic particles, organic structures, and mixed nanostructures. Currently various directions for the research and development of antifungal nanomaterials are undergoing. To improve the antifungal effect, the chemical modification of nanomaterials and combination with the available drugs are two strategies widely used. In addition, optimizing the synthetic process of nanomaterials is also a major method to broaden their antifungal application. This review focuses on the current research progress and cutting-edge technologies of antifungal nanomaterials in the field of pharmacodynamics, synthesis and combination of drugs. The nanomaterial will provide a promising and broadly effective antifungal strategy and represent a potentially repositionable candidate for the treatment of fungal infections.

The incidence of systemic fungal infection is increasing, and millions of people around the world suffer from fungal infections. Candida albicans is one of the most frequently isolated fungal pathogens in clinical settings. As a polymorphic organism, the transition between yeast and hyphae is critical for C. albicans virulence and pathogenesis. However, the mechanism of hyphae-associated virulence remains unclear. Candidalysin is the first human fungal cytolytic peptide toxin originating from the hyphae-specific gene, ECE1. This review will summarize the most recent progress underlying candidalysin-mediated epithelial damage and host defense pathways, which might shed new light on the development of a novel antifungal strategy and early diagnostic biomarker.

Abstract The correlations between microbiota dysbiosis and cancer have gained extensive attention and been widely explored. As a leading cancer diagnosis worldwide, lung cancer poses a great threat to human health. The healthy human lungs are consistently exposed to external environment and harbor a specific pattern of microbiota, sharing many key pathological and physiological characteristics with the intestinal tract. Although previous findings uncovered the critical roles of microbiota in tumorigenesis and response to anticancer therapy, most of them were focused on the intestinal microbiota rather than lung microbiota. Notably, the considerable functions of microbiota in maintaining lung homeostasis should not be neglected as the microbiome dysbiosis may promote tumor development and progression through production of cytokines and toxins and multiple other pathways. Despite the fact that increasing studies have revealed the effect of microbiome on the induction of lung cancer and different disease status, the underlying mechanisms and potential therapeutic strategies remained unclear. Herein, we summarized the recent progresses about microbiome in lung cancer and further discussed the role of microbial communities in promoting lung cancer progression and the current status of therapeutic approaches targeting microbiome to alleviate and even cure lung cancer.

Summary: Successful host colonization by fungi in fluctuating niches requires response and adaptation to multiple environmental stresses. However, our understanding about how fungal species thrive in the gastrointestinal (GI) ecosystem by combing multifaceted nutritional stress with respect to homeostatic host-commensal interactions is still in its infancy. Here, we discover that depletion of the phosphate transceptor Pho84 across multiple fungal species encountered a substantial cost in gastrointestinal colonization. Mechanistically, Pho84 enhances the gastrointestinal commensalism via a dual-action activity, coordinating both phosphate uptake and TOR activation by induction of the transcriptional regulator Try4 and downstream commensalism-related transcription. As such, Pho84 promotes Candida albicans commensalism, but this does not translate into enhanced pathogenicity. Thus, our study uncovers a specific nutrient-dependent dual-action regulatory pathway for Pho84 on fungal commensalism.