Transcription factor PagMYB31 positively regulates cambium activity and negatively regulates xylem development in poplar.

Wood formation involves consecutive developmental steps, including cell division of vascular cambium, xylem cell expansion, secondary cell wall (SCW) deposition, and programmed cell death. In this study, we identified PagMYB31 as a coordinator regulating these processes in Populus alba × Populus glandulosa and built a PagMYB31-mediated transcriptional regulatory network. PagMYB31 mutation caused fewer layers of cambial cells, larger fusiform initials, ray initials, vessels, fiber and ray cells, and enhanced xylem cell SCW thickening, showing that PagMYB31 positively regulates cambial cell proliferation and negatively regulates xylem cell expansion and SCW biosynthesis. PagMYB31 repressed xylem cell expansion and SCW thickening through directly inhibiting wall-modifying enzyme genes and the transcription factor genes that activate the whole SCW biosynthetic program, respectively. In cambium, PagMYB31 could promote cambial activity through TRACHEARY ELEMENT DIFFERENTIATION INHIBITORY FACTOR (TDIF)/PHLOEM INTERCALATED WITH XYLEM (PXY) signaling by directly regulating CLAVATA3/ESR-RELATED (CLE) genes, and it could also directly activate WUSCHEL HOMEOBOX RELATED4 (PagWOX4), forming a feedforward regulation. We also observed that PagMYB31 could either promote cell proliferation through the MYB31-MYB72-WOX4 module or inhibit cambial activity through the MYB31-MYB72-VASCULAR CAMBIUM-RELATED MADS2 (VCM2)/PIN-FORMED5 (PIN5) modules, suggesting its role in maintaining the homeostasis of vascular cambium. PagMYB31 could be a potential target to manipulate different developmental stages of wood formation.

Classification and clinical significance of immunogenic cell death-related genes in Plasmodium falciparum infection determined by integrated bioinformatics analysis and machine learning.

BACKGROUND: Immunogenic cell death (ICD) is a type of regulated cell death that plays a crucial role in activating the immune system in response to various stressors, including cancer cells and pathogens. However, the involvement of ICD in the human immune response against malaria remains to be defined. METHODS: In this study, data from Plasmodium falciparum infection cohorts, derived from cross-sectional studies, were analysed to identify ICD subtypes and their correlation with parasitaemia and immune responses. Using consensus clustering, ICD subtypes were identified, and their association with the immune landscape was assessed by employing ssGSEA. Differentially expressed genes (DEGs) analysis, functional enrichment, protein-protein interaction networks, and machine learning (least absolute shrinkage and selection operator (LASSO) regression and random forest) were used to identify ICD-associated hub genes linked with high parasitaemia. A nomogram visualizing these genes' correlation with parasitaemia levels was developed, and its performance was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In the P. falciparum infection cohort, two ICD-associated subtypes were identified, with subtype 1 showing better adaptive immune responses and lower parasitaemia compared to subtype 2. DEGs analysis revealed upregulation of proliferative signalling pathways, T-cell receptor signalling pathways and T-cell activation and differentiation in subtype 1, while subtype 2 exhibited elevated cytokine signalling and inflammatory responses. PPI network construction and machine learning identified CD3E and FCGR1A as candidate hub genes. A constructed nomogram integrating these genes demonstrated significant classification performance of high parasitaemia, which was evidenced by AUC values ranging from 0.695 to 0.737 in the training set and 0.911 to 0.933 and 0.759 to 0.849 in two validation sets, respectively. Additionally, significant correlations between the expressions of these genes and the clinical manifestation of P. falciparum infection were observed. CONCLUSION: This study reveals the existence of two ICD subtypes in the human immune response against P. falciparum infection. Two ICD-associated candidate hub genes were identified, and a nomogram was constructed for the classification of high parasitaemia. This study can deepen the understanding of the human immune response to P. falciparum infection and provide new targets for the prevention and control of malaria.

Azospirillum isscasi sp. nov., a bacterium isolated from rhizosphere soil of rice.

A Gram-negative and rod-shaped bacterium, designated C340-1T, was isolated and screened from paddy soil in Zhongshan County, Guangxi Province, PR China. This strain grew at 20-42 °C (optimum, 37 °C), pH 5.0-9.0 (optimum, pH 7.0) and 0-4 % (w/v) NaCl (optimum, 0-1 %) on Reasoner's 2A medium. The strain could fix atmospheric nitrogen and acetylene reduction activity was recorded up to 120.26 nmol ethylene h-1 (mg protein)-1. Q-10 was the only isoprenoid quinone component; phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid and an unidentified polar lipid were the major polar lipids. Summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) were the primary cellular fatty acids. The genome of strain C340-1T was 6.18 Mb, and the G+C content was 69.0 mol%. Phylogenetic tree analysis based on 16S rRNA gene and 92 core genes showed that strain C340-1T was closely related to and clustered with the type strains Azospirillum brasilense JCM 1224T, Azospirillum argentinense Az39T, Azospirillum baldaniorum Sp245T and Azospirillum formosense JCM 17639T. The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) values between strain C340-1T and the closely related type strains mentioned above were significantly lower than the threshold values for species classification (95-96 %, 95-96 % and 70 %, respectively). Based on phylogenetic, genomic, phenotypic, physiological and biochemical data, we have reason to believe that C340-1T represents a new species of the genus Azospirillum, for which the name Azospirillum isscasi sp. nov. is proposed. The type strain is C340-1T(=CCTCC AB 2023105T=KCTC 8126T).

Extending Unique 1D Double-Chains to 2D Layers with Birefringent Gain by Introducing a Hydroxyl Group.

It remains a significant hurdle for discovering birefringent materials in the deep ultraviolet (DUV, λ < 200 nm). It is well-known that the OH anions are recognized for their capability to eliminate the dangling bonds from terminal oxygen atoms, promoting the ultraviolet (UV) cutoff edge blueshift and regulating the crystal structure. Here, two new barium hydroxyborates, Ba3B11O18(OH)3(H2O) (BaBOH) and Na2BaB10O16(OH)2(H2O)2 (NaBaBOH), were designed and synthesized while displaying different dimensions. Remarkably, BaBOH presents novel one-dimensional (1D) [B22O37(OH)6]∞ double-chains formed by a new fundamental building block (FBB)[B11O21(OH)3]. NaBaBOH possesses a 2D [B10O16(OH)2]∞ layer with a less common FBB [B10O19(OH)2]. They enrich the structural diversity of hydroxyborates. Moreover, NaBaBOH exhibits a broad transparent window within the DUV spectral range (<190 nm) and possesses a favorable birefringence of 0.064. Furthermore, detailed summaries and structural comparisons have been implemented for all hydroxyborates containing alkali and alkaline-earth metals. This reveals that the OH group modulation strategy can be appropriately employed for the structural design.

The association of leader-member exchange and team-member exchange with nurses' innovative behaviours: A cross-sectional study.

AIM: To measure the association of leader-member exchange and team-member exchange with nurses' innovative behaviours through social exchange theory. BACKGROUND: The field of nursing is actively advocating innovation. Other fields have proven that leader-member exchange and team-member exchange can promote innovative behaviour, but such an association is not clear in nursing. DESIGN: A cross-sectional study. METHODS: A total of 560 nurses were selected from five tertiary hospitals in Henan Province (China) by multistage sampling. Data were collected from a self-report questionnaire. Thirty nurses in the pre-survey were used to verify the validity of the questionnaire. SPSS PROCESS macro was used to verify the association of leader-member exchange and team-member exchange with nurses' innovative behaviours. RESULTS: Leader-member exchange and team-member exchange were significantly associated with nurses' innovative behaviours, and team-member exchange had a mediating effect on the relationship between leader-member exchange and innovative behaviour. CONCLUSIONS: Leader-member exchange and team-member exchange positively affect nurses' innovative behaviours. Leader-member exchange can promote nurses' innovative behaviours through the mediating role of team-member exchange. IMPACT: This study indicated that leader-member exchange and team-member exchange should be given more attention in promoting nurses' innovative behaviours. This finding has implications for the promotion of innovative behaviours in nurses. Leaders need to focus on the innovative needs of nurses and offer support. Meanwhile, leadership training programs are necessary for managers to create positive team relationships. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

Tetraspanin CD82 Correlates with and May Regulate S100A7 Expression in Oral Cancer.

Many metastatic cancers with poor prognoses correlate to downregulated CD82, but exceptions exist. Understanding the context of this correlation is essential to CD82 as a prognostic biomarker and therapeutic target. Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancer. We aimed to uncover the function and mechanism of CD82 in OSCC. We investigated CD82 in human OSCC cell lines, tissues, and healthy controls using the CRISPR-Cas9 gene knockout, transcriptomics, proteomics, etc. CD82 expression is elevated in CAL 27 cells. Knockout CD82 altered over 300 genes and proteins and inhibited cell migration. Furthermore, CD82 expression correlates with S100 proteins in CAL 27, CD82KO, SCC-25, and S-G cells and some OSCC tissues. The 37-50 kDa CD82 protein in CAL 27 cells is upregulated, glycosylated, and truncated. CD82 correlates with S100 proteins and may regulate their expression and cell migration. The truncated CD82 explains the invasive metastasis and poor outcome of the CAL 27 donor. OSCC with upregulated truncated CD82 and S100A7 may represent a distinct subtype with a poor prognosis. Differing alternatives from wild-type CD82 may elucidate the contradictory functions and pave the way for CD82 as a prognostic biomarker and therapeutic target.

Lead Isotope Signatures and Source Identification of Heavy Metals in Vegetable Soils Irrigated with Swine Wastewater of Jiangxi Province, China.

The rapid development of livestock and poultry industry in China has caused serious environment pollution problems. To understand the heavy metals accumulation and identify their sources, 7 heavy metals contents and lead isotope ratios were determined in 24 soil samples from vegetable fields irrigated with swine wastewater in Dongxiang County, Jiangxi Province, China. The results showed that the concentration of Cr, Ni, Cu, Zn, As, Cd and Pb in the swine wastewater irrigated vegetable soils varied from 38.5 to 86.4, 7.57 to 30.6, 20.0 to 57.1, 37.5 to 174, 9.18 to 53.1, 0.043 to 0.274 and 12.8 to 37.1 mg/kg, respectively. The soils were moderately to heavily polluted by As, moderately polluted by Cr, Ni, Cu, Zn and Cd, and unpolluted to moderately polluted by Pb. Sampling soils were classified as moderately polluted according to the Nemerow comprehensive pollution index. Lead isotope and Principal Component Analysis (PCA) analysis indicated that swine wastewater irrigation and atmospheric deposition were the primary sources of the heavy metals.

3D Lithiophilic CuZrAg Metallic Glass Based-Current Collector for High-Performance Lithium Metal Anode.

Lithium metal anodes face several challenges in practical applications, such as dendrite growth, poor cycle efficiency, and volume variation. 3D hosts with lithiophilic surfaces have emerged as a promising design strategy for anodes. In this study, inspiration from the intrinsic isotropy, chemical heterogeneity, and wide tunability of metallic glass (MG) is drew to develop a 3D mesoporous host with a lithiophilic surface. The CuZrAg MG is prepared using the scalable melt-spinning technique and subsequently treated with a simple one-step chemical dealloying method. This resultes in the creation of a host with a homogeneously distributed abundance of lithium affinity sites on the surface. The excellent lithiophilic property and capability for uniform lithium deposition of the 3D CuZrAg electrode have been confirmed through theoretical calculations. Therefore, the 3D CuZrAg electrode displays excellent cyclic stability for over 400 cycles with 96% coulomb efficiency, and ultra-low overpotentials of 5 mV for over 2000 h at 1.0 mA cm-2 and 1.0 mAh cm-2 . Additionally, the full cells partied with either LiFePO4 or LiNi0.8 Co0.1 Mn0.1 O2 cathode deliver exceptional long-term cyclability and rate capability. This work demonstrates the great potential of metallic glass in lithium metal anode application.

Concentration Phase Separation of Substitution-Doped Atoms in TMDCs Monolayer.

The density and spatial distribution of substituted dopants affect the transition metal dichalcogenides (TMDCs) materials properties. Previous studies have demonstrated that the density of dopants in TMDCs increases with the amount of doping, and the phenomenon of doping concentration difference between the nucleation center and the edge is observed, but the spatial distribution law of doping atoms has not been carefully studied. Here, it is demonstrated that the spatial distribution of dopants changes at high doping concentrations. The spontaneous formation of an interface with a steep doping concentration change is named concentration phase separation (CPS). The difference in the spatial distribution of dopants on both sides of the interface can be identified by an optical microscope. This is consistent with the results of spectral analysis and microstructure characterization of scanning transmission electron microscope. According to the calculation results of density functional theory, the chemical potential has two relatively stable energies as the doping concentration increases, which leads to the spontaneous formation of CPS. Understanding the abnormal phenomena is important for the design of TMDCs devices. This work has great significance in the establishment and improvement of the doping theory and the design of the doping process for 2D materials.

Advances in dietary polysaccharides as hypoglycemic agents: mechanisms, structural characteristics, and innovative applications.

Polysaccharides, widely found in various food sources, have gained interest due to their diverse biological activities. This review critically analyzes current research on anti-diabetic polysaccharides, examining their hypoglycemic properties, signaling mechanisms, and relationships between hypoglycemic activity and structural characteristics. It also explores emerging applications of polysaccharides in hyperglycemia and diabetes treatment. Key findings show that polysaccharides' hypoglycemic mechanisms mainly involve repairing islet ß-cells, regulating enzyme activity, reducing oxidative stress, alleviating inflammation, and reshaping gut microbiota. Hypoglycemic activity is mediated through one or more signaling pathways like PI3K/Akt, MAPK, cAMP-PKA, Nrf2, PKC/NF-κB, ubiquitin-proteasome, and PPARs. Additionally, the activity of dietary polysaccharides relies on their source and structural characteristics, such as monosaccharide composition, glycosidic bond types, branching degree, type of modification, and higher-order structures. Additionally, polysaccharide-based formulations, combined with chemotherapy drugs or used as nanocarriers, show significant potential in enhancing therapeutic efficacy, safety, and patient compliance of anti-diabetic drugs. This review offers valuable insights for researchers and healthcare professionals developing innovative diabetes therapies.

The hypoglycemic effect of polysaccharides involves multiple mechanisms.There is intricate relationship between the activity of polysaccharides and their structures.Multiple signaling pathways mediate the hypoglycemic activity of polysaccharides.Polysaccharide-based formulations enhance efficacy and safety of anti-diabetic drugs.

Single-Cell Analysis of the In Vivo Dynamics of Host Circulating Immune Cells Highlights the Importance of Myeloid Cells in Avian Flaviviral Infection.

Ducks are an economically important waterfowl but a natural reservoir for some zoonotic pathogens, such as influenza virus and flaviviruses. Our understanding of the duck immune system and its interaction with viruses remains incomplete. In this study, we constructed the transcriptomic landscape of duck circulating immune cells, the first line of defense in the arthropod-borne transmission of arboviruses, using high-throughput single-cell transcriptome sequencing, which defined 14 populations of peripheral blood leukocytes (PBLks) based on distinct molecular signatures and revealed differences in the clustering of PBLks between ducks and humans. Taking advantage of in vivo sex differences in the susceptibility of duck PBLks to avian tembusu virus (TMUV) infection, a mosquito-borne flavivirus newly emerged from ducks with a broad host range from mosquitos to mammals, a comprehensive comparison of the in vivo dynamics of duck PBLks upon TMUV infection between sexes was performed at the single-cell level. Using this in vivo model, we discovered that TMUV infection reprogrammed duck PBLks differently between sexes, driving the expansion of granulocytes and priming granulocytes and monocytes for antiviral immune activation in males but decreasing the antiviral immune activity of granulocytes and monocytes by restricting their dynamic transitions from steady states to antiviral states with a decrease in the abundance of circulating monocytes in females. This study provides insights into the initial immune responses of ducks to arthropod-borne flaviviral infection and provides a framework for studying duck antiviral immunity.

Analysis of the improvement effect of Astragalus extract on oxidative stress injury in viral myocarditis through STAT3/IL-6.

The objective of this study was to investigate the improvement effect of Astragalus (AS) extract on oxidative stress (OS) and inflammatory response of myocarditis (MYO) cells through the STAT3/IL-6 axis. For this purpose, The MYO model cells prepared by intervening cardiomyocyte HL-1 with Coxsackievirus B3 (CVB3) were divided into four groups: model group, as well as high- (H-), medium- (M-) and low-dose (L-) AS groups treated by 80, 40, and 20 µg/mL AS, respectively. Conventionally cultured cells were set as the normal group. Cell multiplication and apoptosis, as well as levels of Myocardial injury markers (cTnT, BNP and CK), inflammatory cytokines (ICs; TNF-α, IL-1ß and IL-6) and OS indices (SOD, GSH-Px and MDA), were measured. STAT3/IL-6 pathway expression was also observed. Results showed that the model group presented decreased cell multiplication than the normal group, but with increased myocardial injury, apoptosis rate, Caspase3 protein, ICs and OS reaction (P < 0.05); In the three AS-intervened groups, enhanced cell multiplication, while reduced myocardial injury, apoptosis rate, ICs and OS response were observed, especially in H-AS group (P < 0.05). Besides, STAT3 and IL-6 concentrations, statistically increased in the model group, were reduced by AS intervention (P < 0.05). Colivelin, a specific activator of STAT3, further aggravated the apoptosis, inflammatory reaction and OS response of MYO cells (P < 0.05), but its impacts on MYO cells could be reversed by AS. In conclusion, AS can ameliorate MYO, and its mechanism is related to the inhibition of cellular inflammatory response and OS response through the STAT3/IL-6 axis.

An omics data analysis method based on feature linear relationship and graph convolutional network.

Biological networks are known to be highly modular, and the dysfunction of network modules may cause diseases. Defining the key modules from the omics data and establishing the classification model is helpful in promoting the research of disease diagnosis and prognosis. However, for applying modules in downstream analysis such as disease states discrimination, most methods only utilize the node information, and ignore the node interactions or topological information, which may lead to false positives and limit the model performance. In this study, we propose an omics data analysis method based on feature linear relationship and graph convolutional network (LCNet). In LCNet, we adopt a way of applying the difference of feature linear relationships during disease development to characterize physiological and pathological changes and construct the differential linear relation network, which is simple and interpretable from the perspective of feature linear relationship. A greedy strategy is developed for searching the highly interactive modules with a strong discrimination ability. To fully utilize the information of the detected modules, the personalized sub-graphs for each sample based on the modules are defined, and the graph convolutional network (GCN) classifiers are trained to predict the sample labels. The experimental results on public datasets show the superiority of LCNet in classification performance. For Breast Cancer metabolic data, the identified metabolites by LCNet involve important pathways. Thus, LCNet can identify the module biomarkers by feature linear relationship and a greedy strategy, and label samples by personalized sub-graphs and GCN. It provides a new manner of utilizing node (molecule) information and topological information in the defined modules for better disease classification.

Averrhoa carambola L. fruit polyphenols ameliorate hyperlipidemia, hepatic steatosis, and hyperglycemia by modulating lipid and glucose metabolism in mice with obesity.

BACKGROUND: Hyperlipidemia, hepatic steatosis, and hyperglycemia are common metabolic complications of obesity. The objective of the present study is to investigate the in vivo protective effect of Averrhoa carambola L. fruit polyphenols (ACFP) on hyperlipidemia, hepatic steatosis, and hyperglycemia in mice with high-fat diet (HFD)-induced obesity and elucidate the mechanisms of action underlying the beneficial effects of ACFP. Thirty-six specific pathogen-free male C57BL/6J mice (4 weeks old, weighing 17.1-19.9 g) were randomly divided into three groups and fed with a low-fat diet (LFD, 10% fat energy), HFD (45% fat energy), or HFD supplemented with ACFP by intragastric administration for 14 weeks. Obesity-related biochemical indexes and hepatic gene expression levels were determined. The statistical analyses were conducted using one-way analysis of variance (ANOVA) followed by Duncan's multiple range test. RESULTS: The results showed that the body weight gain, serum triglycerides, total cholesterol, glucose, insulin resistance index, and steatosis grade in the ACFP group decreased by 29.57%, 26.25%, 27.4%, 19.6%, 40.32%, and 40%, respectively, compared to the HFD group. Gene expression analysis indicated that ACFP treatment improved the gene expression profiles involved in lipid and glucose metabolism compared to the HFD group. CONCLUSION: ACFP protected from HFD-induced obesity and obesity-associated hyperlipidemia, hepatic steatosis, and hyperglycemia by improving lipid and glucose metabolism in mice. © 2023 Society of Chemical Industry.

Gingival mesenchymal stem cell-derived exosomes are immunosuppressive in preventing collagen-induced arthritis.

Due to the unsatisfied effects of clinical drugs used in rheumatoid arthritis (RA), investigators shifted their focus on the biotherapy. Although human gingival mesenchymal stem cells (GMSC) have the potential to be used in treating RA, GMSC-based therapy has some inevitable side effects such as immunogenicity and tumorigenicity. As one of the most important paracrine mediators, GMSC-derived exosomes (GMSC-Exo) exhibit therapeutic effects via immunomodulation in a variety of disease models, bypassing potential shortcomings of the direct use of MSCs. Furthermore, exosomes are not sensitive to freezing and thawing, and can be readily available for use. GMSC-Exo has been reported to promote tissue regeneration and wound healing, but have not been reported to be effective against autoimmune diseases. We herein compare the immunomodulatory functions of GMSC-Exo and GMSC in collagen-induced arthritis (CIA) model and in vitro CD4+ T-cell co-culture model. The results show that GMSC-Exo has the same or stronger effects compared with GMSC in inhibiting IL-17A and promoting IL-10, reducing incidences and bone erosion of arthritis, via inhibiting IL-17RA-Act1-TRAF6-NF-κB signal pathway. Our results suggest that GMSC-Exo has many advantages in treating CIA, and may offer a promising new cell-free therapy strategy for RA and other autoimmune diseases.

Astrocyte-specific loss of lactoferrin influences neuronal structure and function by interfering with cholesterol synthesis.

Growing evidence indicates that circulating lactoferrin (Lf) is implicated in peripheral cholesterol metabolism disorders. It has emerged that the distribution of Lf changes in astrocytes of aging brains and those exhibiting neurodegeneration; however, its physiological and/or pathological role remains unknown. Here, we demonstrate that astrocyte-specific knockout of Lf (designated cKO) led to decreased body weight and cognitive abnormalities during early life in mice. Accordingly, there was a reduction in neuronal outgrowth and synaptic structure in cKO mice. Importantly, Lf deficiency in the primary astrocytes led to decreased sterol regulatory element binding protein 2 (Srebp2) activation and cholesterol production, and cholesterol content in cKO mice and/or in astrocytes was restored by exogenous Lf or a Srebp2 agonist. Moreover, neuronal dendritic complexity and total dendritic length were decreased after culture with the culture medium of the primary astrocytes derived from cKO mice and that this decrease was reversed after cholesterol supplementation. Alternatively, these alterations were associated with an activation of AMP-activated protein kinase (AMPK) and inhibition of SREBP2 nuclear translocation. These data suggest that astrocytic Lf might directly or indirectly control in situ cholesterol synthesis, which may be implicated in neurodevelopment and several neurological diseases.

Current understanding of the interactions between metal ions and Apolipoprotein E in Alzheimer's disease.

Alzheimer's disease (AD), the most common type of dementia in the elderly, is a chronic and progressive neurodegenerative disorder with no effective disease-modifying treatments to date. Studies have shown that an imbalance in brain metal ions, such as zinc, copper, and iron, is closely related to the onset and progression of AD. Many efforts have been made to understand metal-related mechanisms and therapeutic strategies for AD. Emerging evidence suggests that interactions of brain metal ions and apolipoprotein E (ApoE), which is the strongest genetic risk factor for late-onset AD, may be one of the mechanisms for neurodegeneration. Here, we summarize the key points regarding how metal ions and ApoE contribute to the pathogenesis of AD. We further describe the interactions between metal ions and ApoE in the brain and propose that their interactions play an important role in neuropathological alterations and cognitive decline in AD.

Role of Azole Drugs in Promoting Fungal Cell Autophagy Revealed by an NIR Fluorescence-Based Theranostic Probe.

Autophagy, a widespread degradation system in eukaryotes, plays an important role in maintaining the homeostasis of the cellular environment and the recycling of substances. Optical probes for the tracking of autophagy can be used as an effective tool not only to visualize the autophagy process but also to study autophagy-targeted drugs. Various molecule probes for autophagy of cancer cells emerge but are very limited for that of fungal cells, resulting in the lack of research on antifungal drugs targeting autophagy. To address this issue, we report an azole NIR fluorescence-based theranostic probe AF-1 with antifungal activity that is sensitive to autophagy-associated pH. The unique design of this probe lies in the introduction of both the pH-sensitive fluorophore with a detection range matching the pH range of the autophagy process and the conserved core structural fragment of azole drugs, providing a strategy to investigate the relationship between antifungal drug action and autophagy. As such, AF-1 exhibited excellent spectral properties and was found to target and induce the autophagy of the fungal cell membrane while maintaining moderate antifungal activity. Of note, using this theranostic probe as both a dye and drug, the autophagy process of fungi was visualized in a ratiometric manner, revealing the role of azole antifungal drugs in promoting autophagy to induce fungal cell apoptosis.

Artificial intelligence-assisted system for precision diagnosis of PD-L1 expression in non-small cell lung cancer.

Standardized programmed death-ligand 1 (PD-L1) assessment in non-small cell lung cancer (NSCLC) is challenging, owing to inter-observer variability among pathologists and the use of different antibodies. There is a strong demand for the development of an artificial intelligence (AI) system to obtain high-precision scores of PD-L1 expression in clinical diagnostic scenarios. We developed an AI system using whole slide images (WSIs) of the 22c3 assay to automatically assess the tumor proportion score (TPS) of PD-L1 expression based on a deep learning (DL) model of tumor detection. Tests were performed to show the diagnostic ability of the AI system in the 22c3 assay to assist pathologists and the reliability of the application in the SP263 assay. A robust high-performance DL model for automated tumor detection was devised with an accuracy and specificity of 0.9326 and 0.9641, respectively, and a concrete TPS value was obtained after tumor cell segmentation. The TPS comparison test in the 22c3 assay showed strong consistency between the TPS calculated with the AI system and trained pathologists (R = 0.9429-0.9458). AI-assisted diagnosis test confirmed that the repeatability and efficiency of untrained pathologists could be improved using the AI system. The Ventana PD-L1 (SP263) assay showed high consistency in TPS calculations between the AI system and pathologists (R = 0.9787). In conclusion, a high-precision AI system is proposed for the automated TPS assessment of PD-L1 expression in the 22c3 and SP263 assays in NSCLC. Our study also indicates the benefits of using an AI-assisted system to improve diagnostic repeatability and efficiency for pathologists.

Associations between dietary fiber intake and mortality from all causes, cardiovascular disease and cancer: a prospective study.

OBJECTIVE: Several studies suggest that dietary fiber intake may reduce mortality risk, but this might depend on the fiber types and the evidence regarding the role of soluble fiber or insoluble fiber on death risk remain limited and inconsistent. Therefore, this study aimed to comprehensively evaluate multiple types of dietary fiber intake on mortality from all causes, cardiovascular disease and cancer in the large-scale Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. METHODS: A multivariate Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: This study finally included 86,642 participants with 17,536 all-cause deaths, 4842 cardiovascular deaths and 5760 cancer deaths identified after a total of 1,444,068 follow-up years. After adjusting for potential confounders, dietary total fiber intake was statistically significantly inversely associated with all-cause death (Q5 vs Q1: HR 0.71, 95% CI 0.66-0.75; P for trend < 0.001), cardiovascular death (Q5 vs Q1: HR 0.73, 95% CI 0.65-0.83; P for trend < 0.001) and cancer mortality (Q5 vs Q1: HR 0.77, 95% CI 0.69-0.86; P for trend < 0.001). Similar results were observed for both insoluble and soluble fiber intake. Restricted cubic spline model analysis suggested that there was a nonlinear association of dietary fiber intake with mortality risk (all P for nonlinearity < 0.05). CONCLUSIONS: In this large nationally representative sample of US adult population, intakes of total fiber, soluble fiber, and insoluble fiber were associated with lower risks of all-cause, cardiovascular and cancer mortality.