Endophytic Fungi Volatile Organic Compounds as Crucial Biocontrol Agents Used for Controlling Fruit and Vegetable Postharvest Diseases.

Fruits and vegetables are an important part of the human diet, but during transportation and storage, microbial pathogens attack and spoil fruits and vegetables, causing huge economic losses to agriculture. Traditionally used chemical fungicides leave chemical residues, leading to environmental pollution and health risks. With the emphasis on food safety, biocontrol agents are attracting more and more attention due to their environmental friendliness. Endophytic fungi are present in plant tissues and do not cause host disease. The volatile organic compounds (VOCs) they produce are used to control postharvest diseases due to their significant antifungal activity, as well as their volatility, safety and environmental protection characteristics. This review provides the concept and characterization of endophytic fungal VOCs, concludes the types of endophytic fungi that release antifungal VOCs and their biological control mechanisms, as well as focuses on the practical applications and the challenges of applying VOCs as fumigants. Endophytic fungal VOCs can be used as emerging biocontrol resources to control postharvest diseases that affect fruits and vegetables.

ADAMTS4 is a crucial proteolytic enzyme for versican cleavage in the amnion at parturition.

Hyalectan cleavage may play an important role in extracellular matrix remodeling. However, the proteolytic enzyme responsible for hyalectan degradation for fetal membrane rupture at parturition remains unknown. Here, we reveal that versican (VCAN) is the major hyalectan in the amnion, where its cleavage increases at parturition with spontaneous rupture of membrane. We further reveal that ADAMTS4 is a crucial proteolytic enzyme for VCAN cleavage in the amnion. Inflammatory factors may enhance VCAN cleavage by inducing ADAMTS4 expression and inhibiting ADAMTS4 endocytosis in amnion fibroblasts. In turn, versikine, the VCAN cleavage product, induces inflammatory factors in amnion fibroblasts, thereby forming a feedforward loop between inflammation and VCAN degradation. Mouse studies show that intra-amniotic injection of ADAMTS4 induces preterm birth along with increased VCAN degradation and proinflammatory factors abundance in the fetal membranes. Conclusively, there is enhanced VCAN cleavage by ADAMTS4 in the amnion at parturition, which can be reenforced by inflammation.

Transient CD4+ T cell depletion during suppressive ART reduces the HIV reservoir in humanized mice.

Lifelong treatment is required for people living with HIV as current antiretroviral therapy (ART) does not eradicate HIV infection. Latently infected cells are essentially indistinguishable from uninfected cells and cannot be depleted by currently available approaches. This study evaluated antibody mediated transient CD4+ T cell depletion as a strategy to reduce the latent HIV reservoir. Anti-CD4 antibodies effectively depleted CD4+ T cells in the peripheral blood and tissues of humanized mice. We then demonstrate that antibody-mediated CD4+ T cell depletion of HIV infected ART-suppressed animals results in substantial reductions in cell-associated viral RNA and DNA levels in peripheral blood cells over the course of anti-CD4 antibody treatment. Recovery of CD4+ T cells was observed in all tissues analyzed except for the lung 26 days after cessation of antibody treatment. After CD4+ T cell recovery, significantly lower levels of cell-associated viral RNA and DNA were detected in the tissues of anti-CD4 antibody-treated animals. Further, an 8.5-fold reduction in the levels of intact HIV proviral DNA and a 3.1-fold reduction in the number of latently infected cells were observed in anti-CD4-antibody-treated animals compared with controls. However, there was no delay in viral rebound when ART was discontinued in anti-CD4 antibody-treated animals following CD4+ T cell recovery compared with controls. Our results suggest that transient CD4+ T cell depletion, a long-standing clinical intervention that might have an acceptable safety profile, during suppressive ART can reduce the size of the HIV reservoir in humanized mice.

Immune cells within tertiary lymphoid structures are associated with progression-free survival in patients with locoregional recurrent breast cancer.

INTRODUCTION: Locoregional recurrent breast cancers have a poor prognosis. Little is known about the prognostic impact of immune microenvironment, and tertiary lymphoid structures (TLSs) in particular have not been reported. Thus, we aimed to characterize the immune microenvironment in locoregional recurrent breast tumors and to investigate its relationship with prognosis. METHODS: We retrospectively included 112 patients with locoregional recurrent breast cancer, and hematoxylin-eosin staining and immunohistochemical staining (CD3, CD4, CD8, CD19, CD38, and CD68) were performed on locoregional recurrent tumor samples. The association of immune cells and TLSs with progression-free survival (PFS) were analyzed by survival analysis. RESULTS: We found more immune cells in the peritumor than stroma. After grouping according to estrogen receptor (ER) status, a low level of peritumoral CD3+ cells in ER+ subgroup (p = 0.015) and a low level of stromal CD68+ cells in ER- subgroup (p = 0.047) were both associated with longer PFS. TLSs were present in 68% of recurrent tumors, and CD68+ cells within TLSs were significantly associated with PFS as an independent prognostic factor (p = 0.035). TLSs and immune cells (CD3, CD38, and CD68) within TLSs were associated with longer PFS in ER- recurrent tumors (p = 0.044, p = 0.012, p = 0.050, p < 0.001, respectively), whereas CD38+ cells within TLSs were associated with shorter PFS in ER+ recurrent tumors (p = 0.037). CONCLUSION: Our study proposes potential predictors for the clinical prognosis of patients with locoregional recurrent breast cancer, emphasizing the prognostic value of immune cells within TLSs, especially CD68+ cells.

Percutaneous microwave ablation combined with endocrine therapy versus standard therapy for elderly patients with HR-positive and HER2-negative invasive breast cancer: a propensity score-matched analysis of a multi-center, prospective cohort study.

Background: There is a growing trend to apply minimally invasive local treatments for elderly patients with early-stage breast cancer. As a minimally invasive thermal therapy, microwave ablation (MWA) has been attempted to treat breast cancer of small lesions, but its long-term local efficacy on elderly patients has seldom been reported. In this study, we aimed to compare outcomes of MWA combined with endocrine therapy to standard surgery combined with adjuvant therapy in the treatment of hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer for elderly patients. Methods: This prospective multi-center cohort study enrolled patients over 70 years old diagnosed with HR-positive and HER2-negative early-stage invasive breast cancer between January 2016 and July 2021. Patients chose either non-randomized to undergo MWA combined with endocrine therapy (MWA group) or standard surgery combined with adjuvant therapy (surgery group). Endpoints for the comparisons were disease-free survival (DFS), overall survival (OS) and length of hospital stay (LOS) after adjusting for previously reported risk factors using propensity score matching (1:3). Results: Of the enrolled 132 patients, 33 were in the MWA group and 99 were in the surgery group. MWA was successfully performed in all cases, and technical effectiveness was achieved in all cases. With a median follow-up of 31 months, only one case had local recurrence 23 months after MWA. MWA combined with endocrine therapy and standard surgery combined adjuvant therapy for elderly patients with breast cancer achieved similar DFS [hazard ratio, 0.536; 95% confidence interval (CI): 0.128-2.249] and OS (hazard ratio, 0.537; 95% CI: 0.089-3.235). Besides, MWA had much shorter LOS than standard surgery (7.1 versus 13.0 days, P<0.001). Conclusions: MWA combined with endocrine therapy and standard surgery combined with adjuvant therapy for elderly breast cancer patients achieved similar outcomes. MWA combined with endocrine may be a feasible treatment strategy for elderly patients with HR-positive and HER2-negative invasive breast cancer.

Feasibility and efficacy of ultrasound-guided high-intensity focused ultrasound of breast fibroadenoma.

OBJECTIVE: This nonrandomized prospective clinical trial aimed to assess the efficacy, safety and follow-up outcomes of ultrasound-guided high-intensity focused ultrasound (USgHIFU) surgery in patients with breast fibroadenoma. METHODS: With the approval of the institutional ethics committee and written informed consent, a total of 113 patients diagnosed with breast fibroadenoma by core-needle biopsy in our hospital were recruited. USgHIFU surgery was performed under local anesthesia. Contrast-enhanced ultrasound (CEUS) or contrast-enhanced MRI (CEMRI) was performed to evaluate the nonperfused volume (NPV). The patients were followed up with physical examination and ultrasound imaging. RESULTS: The clinical outcome of 85 patients with 147 fibroadenomas with a follow-up time of more than 3 months was analyzed in this study. Fifty-two patients had one lesion, twenty-one patients had two lesions and twelve patients had more than two lesions. During USgHIFU, the median localization time for all fibroadenomas was 3 (interquartile range: 1, 5) min, and the median treatment time was 9 (interquartile range: 5, 15) min. Under local anesthesia, all the patients tolerated the treatment well. No serious epidermal burns were observed in any of the patients. Based on CEUS or CEMRI imaging evaluation, the median NPV ratio was 100% (interquartile range: 79.2%, 116.8%). The VRR were 26.77 ± 50.05%, 50.22 ± 42.01% and 72.74 ± 35.39% at 3-6 months, 6-12 months and >12 months, respectively, which showed significant statistical difference (p < .001). CONCLUSION: Ultrasound-guided HIFU surgery is an effective and safe noninvasive alternative technique for the treatment of breast fibroadenoma.

A germ-free humanized mouse model shows the contribution of resident microbiota to human-specific pathogen infection.

Germ-free (GF) mice, which are depleted of their resident microbiota, are the gold standard for exploring the role of the microbiome in health and disease; however, they are of limited value in the study of human-specific pathogens because they do not support their replication. Here, we develop GF mice systemically reconstituted with human immune cells and use them to evaluate the role of the resident microbiome in the acquisition, replication and pathogenesis of two human-specific pathogens, Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). Comparison with conventional (CV) humanized mice showed that resident microbiota enhance the establishment of EBV infection and EBV-induced tumorigenesis and increase mucosal HIV acquisition and replication. HIV RNA levels were higher in plasma and tissues of CV humanized mice compared with GF humanized mice. The frequency of CCR5+ CD4+ T cells throughout the intestine was also higher in CV humanized mice, indicating that resident microbiota govern levels of HIV target cells. Thus, resident microbiota promote the acquisition and pathogenesis of two clinically relevant human-specific pathogens.

Loss of In Vivo Replication Fitness of HIV-1 Variants Resistant to the Tat Inhibitor, dCA.

HIV resistance to the Tat inhibitor didehydro-cortistatin A (dCA) in vitro correlates with higher levels of Tat-independent viral transcription and a seeming inability to enter latency, which rendered resistant isolates more susceptible to CTL-mediated immune clearance. Here, we investigated the ability of dCA-resistant viruses to replicate in vivo using a humanized mouse model of HIV infection. Animals were infected with WT or two dCA-resistant HIV-1 isolates in the absence of dCA and followed for 5 weeks. dCA-resistant viruses exhibited lower replication rates compared to WT. Viral replication was suppressed early after infection, with viral emergence at later time points. Multiplex analysis of cytokine and chemokines from plasma samples early after infection revealed no differences in expression levels between groups, suggesting that dCA-resistance viruses did not elicit potent innate immune responses capable of blocking the establishment of infection. Viral single genome sequencing results from plasma samples collected at euthanasia revealed that at least half of the total number of mutations in the LTR region of the HIV genome considered essential for dCA evasion reverted to WT. These results suggest that dCA-resistant viruses identified in vitro suffer a fitness cost in vivo, with mutations in LTR and Nef pressured to revert to wild type.

Research progress of volatile organic compounds produced by plant endophytic bacteria in control of postharvest diseases of fruits and vegetables.

Pathogen infestation results in significant losses of fruits and vegetables during handling, transportation, and storage. The use of synthetic fungicides has been a common measure for controlling plant pathogens. However, their excessive use of chemicals has led to increased environmental pollution, leaving large amounts of chemicals in agricultural products, posing a threat to human and animal health. There is now an increasing amount of research activities to explore safer and more innovative ways to control plant pathogens. In this regard, endophytic bacteria contribute significantly. Endophytic bacteria are ubiquitous in the internal tissues of plants without causing damage or disease to the host. Due to their high volatility and difficulties in residue in fruits and vegetables, volatile organic chemicals (VOCs) produced by endophytic bacteria have received a lot of attention in recent years. VOCs are a potential biofumigant for the effective control of postharvest fruits and vegetables diseases. This review focuses mainly on the recent progress in using endophytic bacteria VOCs to control post-harvest fruits and vegetables disease. This review provides a brief overview of the concept, characteristics, and summarises the types, application effect, and control mechanisms of endophytic bacterial VOCs. The research area that is being developed has great application value in agriculture and living practice.

Combining primary tumor features derived from conventional and contrast-enhanced ultrasound facilitates the prediction of positive axillary lymph nodes in Breast Imaging Reporting and Data System category 4 malignant breast lesions.

PURPOSE: To determine whether the primary tumor features derived from conventional ultrasound (US) and contrast-enhanced US (CEUS) facilitate the prediction of positive axillary lymph nodes (ALNs) in breast cancer diagnosed as Breast Imaging Reporting and Data System (BI-RADS) category 4. METHODS: A total of 240 women with breast cancer who underwent preoperative conventional US, strain elastography, and CEUS between September 2016 and December 2019 were included. The multiple parameters of the primary tumor were obtained, and univariate and multivariate analyses were performed to predict positive ALNs. Then three prediction models (conventional US features, CEUS features, and the combined features) were developed, and the diagnostic performance was evaluated with receiver operating characteristic curves. RESULTS: On conventional US, the traits of large size and the non-circumscribed margin of the primary tumor were marked as two independent predictors. On CEUS, the features of vessel perforation or distortion and the enhanced range of the primary tumor were marked as two independent predictors for positive ALNs. Three prediction models were then developed: model A (conventional US features), model B (CEUS features), and model C (model A plus B). Model C yielded the highest area under the curve (AUC) of 0.82 [95% confidence interval (CI), 0.75-0.88] compared with model A (AUC 0.74; 95% CI, 0.68-0.81; P = 0.008) and model B (AUC 0.72; 95% CI, 0.65-0.80; P < 0.001) as per the DeLong test. CONCLUSION: CEUS, as a non-invasive examination technique, can be used to predict ALN metastasis. Combining conventional US and CEUS may produce favorable predictive accuracy for positive ALNs in BI-RADS category 4 breast cancer.

Efficient removal of heavy metals by endophytic bacteria Staphylococcus succinus H3.

AIMS: Heavy metal pollution is a serious and difficult environmental problem. With increasing heavy metal content in industrial wastewater, an environmentally friendly and efficient treatment method must be identified. METHODS AND RESULTS: Considering the ability of endophytic bacteria to adsorb metal ions, this paper explored the heavy metal resistance, adsorption, and adsorption mechanisms and performance of S. succinus H3, an endophytic bacterium. S. succinus H3 exhibited metal resistance at 4 mM Cu2+ and 5 mM Mg2+. The adsorption rate of Cu2+ and Mg2+ ions by the live/dead strain was approximately 70%, and the adsorption capacity was positively correlated with the metal ion concentration. The kinetics and isothermal models were used to study the process of S. succinus H3 adsorption on Cu2+. It exhibits a good correlation with the Freundlich isothermal model. The N-H group, protein C=O group, polysaccharide C-O group, O-H group and some lipids are the main functional groups in the cell wall. S. succinus H3 may bond with the amine group to adsorb Mg2+ through complexation/coordination and may form a copper complex after adsorbing Cu2+. S. succinus H3 has a live adsorption rate of 15% in eight mixed metal ion systems at a 50 mg/L concentration. The study results can lay a foundation for expanding the bacterial resource pool of pollutant treatment and improving the efficiency for sewage treatment. The high heavy metal adsorption capacity of microorganisms has a decisive role in industrial wastewater treatment by microorganisms. Such microorganisms with high metal resistance and adsorption capacity to heavy metals can thrive in industrial wastewater, remove heavy metals efficiently, and greatly improve the efficiency of wastewater treatment. CONCLUSION: The study results can lay a theoretical foundation for the use of S. succinus H3 to biologically treat heavy metal wastewater in the future.

The synergistic effect and mechanisms of flavonoids and polysaccharides from Houttuynia cordata on H1N1-induced pneumonia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb. (HC, Saururaceae family) is a classical Traditional Chinese Medicine used to treat pneumonia clinically. The total flavonoids (HCF) and polysaccharides (HCP) are key medicinal components of H. cordata involved in its beneficial effect on viral pneumonia. AIM OF THE STUDY: The purpose of the study is to investigate the synergistic or complementary effects of combination of HCF and HCP on viral pneumonia as well as the mechanisms underlying. MATERIALS AND METHODS: HCF or HCP were administrated separately or combined in different proportions on influenza virus H1N1 - infected mice. The survival and lung weight of mice were recorded. The synergistic effect on HCF and HCP combination was calculated by Chou-Talalay method. H&E staining was performed to detect lung histomorphology. Western blot, immunohistochemistry and enzyme linked immunosorbent assay were done to analyze the representative protein expression in lung and intestine tissues. AB - PAS staining on intestine tissue sections was performed to evaluate the histopathology of intestines. Bacterial genomic DNA was extracted and sequenced for gut microbiota analysis. RESULTS: In H1N1 lethally infected mice, the combined administration of HCF and HCP significantly increased the survival rate and prolonged the life span of mice, compared with mono-drug therapy. The viral pneumonia was remarkably improved by HCF and HCP combination reflected by lower lung index, more intact lung morphology, and less inflammatory cells and mediators. Furthermore, the combination of HCF and HCP regulated intestinal microbiota, significantly reduced the proportion of pathogenic Proteobacteria and the secretion of proinflammatory cytokine in gut. The combined HCF and HCP showed synergistic effect on reducing lung and intestine injury. The complementary interaction was also found in HCF and HCP combined therapy, as HCF provided the significant antiviral activity and HCP markedly improved intestinal physical barrier and increased the protein expression involving removal of edema. CONCLUSIONS: Our findings indicated that combination of HCF and HCP from H. cordata synergistically alleviated H1N1-induced viral pneumonia in mice via multimodal regulation of both pulmonary and intestinal homeostasis, which might imply novel therapeutic strategy for treating viral pneumonia.

ER-phagy Is Involved in the Degradation of Collagen I by IL-1ß in Human Amnion in Parturition.

The process of parturition is associated with inflammation within the uterine tissues, and IL-1ß is a key proinflammatory cytokine involved. Autophagy is emerging as an important pathway to remove redundant cellular components. However, it is not known whether IL-1ß employs the autophagy pathway to degrade collagen, thereby participating in membrane rupture at parturition. In this study, we investigated this issue in human amnion. Results showed that IL-1ß levels were significantly increased in human amnion obtained from deliveries with spontaneous labor and membrane rupture, which was accompanied by decreased abundance of COL1A1 and COL1A2 protein but not their mRNA, the two components of collagen I. Consistently, IL-1ß treatment of cultured primary human amnion fibroblasts reduced COL1A1 and COL1A2 protein but not their mRNA abundance along with increased abundance of autophagy activation markers, including the microtubule-associated protein L chain 3ß II/I ratio and autophagy-related 7 (ATG7) in the cells. The reduction in COL1A1 and COL1A2 protein abundance induced by IL-1ß could be blocked by the lysosome inhibitor chloroquine or small interfering RNA-mediated knockdown of ATG7 or ER-phagy receptor FAM134C, suggesting that FAM134C-mediated ER-phagy was involved in IL-1ß-induced reduction in COL1A1 and COL1A2 protein in amnion fibroblasts. Consistently, levels of L chain 3ß II/I ratio, ATG7, and FAM134C were significantly increased in human amnion obtained from deliveries with spontaneous labor and membrane rupture. Conclusively, increased IL-1ß abundance in human amnion may stimulate ER-phagy-mediated COL1A1 and COL1A2 protein degradation in amnion fibroblasts, thereby participating in membrane rupture at parturition.

ER-phagy Is Involved in the Degradation of Collagen I by IL-1ß in Human Amnion in Parturition.

The process of parturition is associated with inflammation within the uterine tissues, and IL-1ß is a key proinflammatory cytokine involved. Autophagy is emerging as an important pathway to remove redundant cellular components. However, it is not known whether IL-1ß employs the autophagy pathway to degrade collagen, thereby participating in membrane rupture at parturition. In this study, we investigated this issue in human amnion. Results showed that IL-1ß levels were significantly increased in human amnion obtained from deliveries with spontaneous labor and membrane rupture, which was accompanied by decreased abundance of COL1A1 and COL1A2 protein but not their mRNA, the two components of collagen I. Consistently, IL-1ß treatment of cultured primary human amnion fibroblasts reduced COL1A1 and COL1A2 protein but not their mRNA abundance along with increased abundance of autophagy activation markers, including the microtubule-associated protein L chain 3ß II/I ratio and autophagy-related 7 (ATG7) in the cells. The reduction in COL1A1 and COL1A2 protein abundance induced by IL-1ß could be blocked by the lysosome inhibitor chloroquine or small interfering RNA-mediated knockdown of ATG7 or ER-phagy receptor FAM134C, suggesting that FAM134C-mediated ER-phagy was involved in IL-1ß-induced reduction in COL1A1 and COL1A2 protein in amnion fibroblasts. Consistently, levels of L chain 3ß II/I ratio, ATG7, and FAM134C were significantly increased in human amnion obtained from deliveries with spontaneous labor and membrane rupture. Conclusively, increased IL-1ß abundance in human amnion may stimulate ER-phagy-mediated COL1A1 and COL1A2 protein degradation in amnion fibroblasts, thereby participating in membrane rupture at parturition.

The antifungal activity of a serine protease and the enzyme production of characteristics of Bacillus licheniformis TG116.

The growth of Phytophthora capsica, Rhizoctonia solani, Fusarium graminearum, Fusarium oxysporum and Botrytis cinerea were all inhibited by the fermentation supernatant of Bacillus licheniformis TG116, a biocontrol strain isolated from Typhonium giganteum Engl. previously with broad-spectrum resistance to plant pathogens. The fermentation supernatant of the TG116 has a great stability on temperature and UV, and shows the biological activity of protease and cellulase. The antifungal protease produced by B. licheniformis TG116 was purified to homogeneity by ammonium sulfate precipitation, DEAE Sepharose Fast Flow column chromatography and Sephadex G-50 column chromatography. The inhibition of protease by the three surfactants increased with increasing concentration inhibition. Among these surfactants, EDTA showed the strongest inhibition, with only 25% protein activity at a concentration of 1.1 mmol·L-1. Gene amplification verified the presence of a gene fragment of serine protease in the strain TG116. The antimicrobial substance isolated from the fermentation broth of TG116 is a serine protease component.

Cortisol Stimulates Local Progesterone Withdrawal Through Induction of AKR1C1 in Human Amnion Fibroblasts at Parturition.

Fetal membrane activation is seen as being one of the crucial triggering components of human parturition. Increased prostaglandin E2 (PGE2) production, a common mediator of labor onset in virtually all species, is recognized as one of the landmark events of membrane activation. Fetal membranes are also equipped with a high capacity of cortisol regeneration by 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1), and the cortisol regenerated potently induces PGE2 synthesis, an effect normally suppressed by progesterone during gestation. There is no precipitous decline of progesterone synthesis in human parturition. It is intriguing how this suppression is lifted in parturition. Here, we investigated this issue by using human amnion tissue and primary amnion fibroblasts which synthesize the most PGE2 in the fetal membranes. Results showed that the expression of 11ß-HSD1 and aldo-keto reductase family 1 member C1 (AKR1C1), a progesterone-inactivating enzyme, increased in parallel in human amnion tissue with gestational age toward the end of gestation and at parturition. Cortisol induced AKR1C1 expression via the transcription factor CCAAT enhancer binding protein δ (C/EBPδ) in amnion fibroblasts. Inhibition of AKR1C1 not only blocked progesterone catabolism induced by cortisol, but also enhanced the suppression of cortisol-induced cyclooxygenase-2 (COX-2) expression by progesterone in amnion fibroblasts. In conclusion, our results indicate that cortisol regenerated in the fetal membranes triggers local progesterone withdrawal through enhancement of AKR1C1-mediated progesterone catabolism in amnion fibroblasts, so that the suppression of progesterone on the induction of COX-2 expression and PGE2 synthesis by cortisol can be lifted for parturition.

Volatile organic compounds produced by Bacillus velezensis L1 as a potential biocontrol agent against postharvest diseases of wolfberry.

Volatile organic compounds (VOCs) produced by antagonistic microorganisms have good biocontrol prospects against postharvest diseases. Infection caused by Alternaria iridiaustralis and 10 other significant fungal diseases can be successfully inhibited by VOCs produced by an identified and screened endophytic strain L1 (Bacillus velezensis). This study revealed the in vivo and in vitro biocontrol effects of VOCs released by B. velezensis L1 on A. iridiaustralis, a pathogenic fungus responsible for rot of wolfberry fruit. The inhibition rates of VOCs of B. velezensis L1 on the mycelial growth of A. iridiaustralis in vitro were 92.86 and 90.30%, respectively, when the initial inoculum concentration on the plate was 1 × 109 colony forming unit (CFU)/ml. Spore germination and sporulation were 66.89 and 87.96%, respectively. VOCs considerably decreased the wolfberry's disease index and decay incidence in vivo. Scanning electron microscopy revealed that the morphological and structural characteristics of A. iridiaustralis could be altered by VOCs. Ten VOCs were identified through headspace-gas chromatography-ion mobility spectrometry. Pure chemical tests revealed that 2.3-butanedione had the strongest antifungal effects, totally inhibiting A. iridiaustralis in wolfberry fruit at a 60 µl/L concentration. The theory underpinning the potential application of VOCs from B. velezensis is provided herein. This is also the first study to document the antifungal capabilities of the B. velezensis strain on postharvest wolfberry fruit. GRAPHICAL ABSTRACT.

BCL-2 inhibitor synergizes with PI3Kδ inhibitor and overcomes FLT3 inhibitor resistance in acute myeloid leukaemia.

Inhibitors targeting the antiapoptotic molecule BCL-2 have therapeutic potential for the treatment of acute myeloid leukaemia (AML); however, BCL-2 inhibitors such as venetoclax exhibit limited monotherapy efficacy in relapsed or refractory human AML. PI3Kδ/AKT signalling has been shown to be constitutively active in AML patients. Here, we demonstrate that the combination of BCL-2 and PI3Kδ inhibitors exerts synergistic antitumour effects both in vitro and in vivo in AML. Cotreatment with venetoclax and the specific PI3Kδ inhibitor idelalisib significantly enhanced antiproliferative effects and induced caspase-dependent apoptosis in a panel of AML cell lines. The synergistic effects were mechanistically based on the inactivation of AKT/4E-BP-1 signalling and the reduction of MCL-1 expression, which diminished the binding of Bim to MCL-1. Notably, compared with the parental FLT3-ITD-positive MV-4-11, the acquired FLT3 inhibitor quizartinib-resistant xenograft model carrying the F691L mutation, exhibited a markedly higher sensitivity to venetoclax. Furthermore, venetoclax combined with idelalisib led to tumour regression in all animals in this quizartinib-resistant AML model. Thus, these data indicate that combined inhibition of BCL-2 and PI3Kδ may be a promising strategy in AML, especially for patients with FLT3-ITD and/or FLT3-TKD mutations.

Isolation, Identification and Characteristic Analysis of Plant Endophyte Electrogenic Bacteria Shinella zoogloeoides SHE10.

Electroactive microorganisms play a significant role in microbial fuel cells (MFCs). These devices are environmentally friendly and can turn large quantities of organic material into renewable energy based on microbial diversity. Based on broad microbial diversity, it is necessary to obtain a comprehensive understanding of their resource distribution and to discover potential resources. In this study, sweet potato tissues were selected to isolate endophytic bacteria, and the electrochemical activity potential of those bacteria was evaluated by high-throughput screening with a WO3 nanoprobe. This study was screened and obtained a strain SHE10 with electrochemical performance from the rhizome of sweet potato by a WO3 nanoprobe, which was identified as Shinella zoogloeoides. After nearly 600 h of voltage monitoring and cyclic voltammetry analysis, the results showed that the average voltage of S. zoogloeoides SHE10 reached 122.5 mV in stationary period. The maximum power density is 78.3 ± 1.8 mW/m2, and the corresponding current density is 223.0 mA/m2. The good redox reaction also indicated that the strain had good electrical activity. Its electron transfer mode was diverse, but its power generation mechanism still needs to be further discussed. The study of S. zoogloeoides SHE10 provides scientific theoretical reference for expanding the resource pool of electroproducing bacteria and the types of electroproducing microorganisms.