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AimsHeavy 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 resultsConsidering 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.ConclusionThe study results can lay a theoretical foundation for the use of S. succinus H3 to biologically treat heavy metal wastewater in the future.

Adenosine is an immunosuppressive factor in the tumor microenvironment mainly through activation of the A2A adenosine receptor (A2AR), which is a mechanism hijacked by tumors to escape immune surveillance. Small-molecule A2AR antagonists are being evaluated in clinical trials as immunotherapeutic agents, but their efficacy is limited as standalone therapies. To enhance the antitumor effects of A2AR antagonists, dual-acting compounds incorporating A2AR antagonism and histone deacetylase (HDAC) inhibitory actions were designed and synthesized, based on co-crystal structures of A2AR. Compound 24e (IHCH-3064) exhibited potent binding to A2AR (Ki = 2.2 nM) and selective inhibition of HDAC1 (IC50 = 80.2 nM), with good antiproliferative activity against tumor cell lines in vitro. Intraperitoneal administration of 24e (60 mg/kg, bid) inhibited mouse MC38 tumor growth with a tumor growth inhibition rate of 95.3%. These results showed that dual-acting compounds targeting A2AR and HDAC are potentially immunotherapeutic agents that are worth further exploring.

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 serine protease and cellulase. The antifungal protease produced by Bacillus licheniformis TG116 was purified to homogeneity by ammonium sulfate precipitation, DEAE Sepharose Fast Flow column chromatography and Sephadex G-50 column chromatography. When Colletotrichum capsici was used as an indicator strain, the protease exhibited great antifungal activity at a pH range from 5.0 to 11.0 and temperature at no higher than 60°C. 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. The serine protease isolated and purified from B. licheniformis TG116 has a great antifungal activity.

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 WO

Bacillus subtilis strain CL2 is antagonistic to wolfberry postharvest pathogenic fungi. In this study, we isolated and screened this strain for in vitro experiments. The result of the two-sealed-base-plates method revealed that volatile organic compounds (VOCs) emitted from the strain CL2 inhibited the hyphal growth of four pathogenic fungi Mucor circinelloides LB1, Fusarium arcuatisporum LB5, Alternaria iridiaustralis LB7, and Colletotrichum fioriniae LB8. After exposure to VOCs for 5 days, the hyphal growth of the pathogen C. fioriniae LB8 was inhibited by 73%. Scanning electron microscopy revealed that the VOCs produced by B. subtilis CL2 caused the mycelium morphology of the pathogenic fungi to deform, twist, fold, and shrink. In the in vivo experiments, we noticed that VOCs could significantly reduce the weight loss rate of wolfberry fruits caused by the pathogenic fungus M. circinelloides LB1 and that the decay incidence rate were caused by the pathogenic fungi F. arcuatisporum LB5, A. iridiaustralis LB7, and C. fioriniae LB8. On the basis of the headspace-gas chromatography-ion mobility spectrometry analysis, seven VOCs produced by strain CL2 were identified. Among them, 2,3-butanedione and 3-methylbutyric acid are the main antifungal active substances. This study investigated the antifungal properties of VOCs produced by the strain CL2 on postharvest pathogenic fungi isolated from wolfberry fruits both in vivo and in vitro, thereby providing the theoretical basis for its future applications.

Wei Liu,1,* Min Zong,2,* Hai-yan Gong,1,* Li-jun Ling,3 Xin-hua Ye,1 Shui Wang,3 Cui-ying Li1 1Department of Ultrasound, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 3Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cui-ying LiDepartment of Ultrasound, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, People’s Republic of ChinaTel +86-15062260771Email lcy_njmu@163.comShui WangDepartment of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, People’s Republic of ChinaTel +86-13701458115Email wangshui_njmu@163.comBackground: Contrast-enhanced ultrasound (CEUS) can provide angiogenesis information about breast lesions; however, its diagnostic performance in comparison with that of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has not been systematically investigated. This study aimed to evaluate the diagnostic efficacy of CEUS and DCE-MRI in mass-like and non-mass-like enhancement types of breast lesions.Material and Methods: A retrospective study was conducted on 252 patients with breast lesions who underwent CEUS and DCE-MRI before surgery between January 2016 and February 2020. Histopathological results were used as reference standards. All patients were classified into mass-like and non-mass-like enhancement lesion groups. The mass-like lesion group was further divided into three categories according to different sizes (group 1: < 10 mm, group 2: 10– 20 mm, and group 3: > 20 mm). Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curve were analyzed to assess the diagnostic performance of these two modalities.Results: For mass-like breast lesions, DCE-MRI (Az=0.981) manifested better diagnostic performance than CEUS (Az=0.940) in medium-sized (10– 20 mm) tumors (Z=2.018, P=0.043), but both had similar diagnostic performance in smaller (< 10 mm) and larger (> 20 mm) tumors (P=0.717, P=0.394). For non-mass-like enhancement lesions, CEUS and DCE-MRI showed no significant difference (Z=1.590, P=0.119) and revealed good diagnostic performance (Az=0.859, Az=0.947) in differentiating the two groups.Conclusion: For mass-like breast lesions, DCE-MRI showed better diagnostic performance than CEUS in differentiating benign and malignant tumors of medium-sizes (10– 20mm) but not of smaller (< 10mm) and larger (> 20 mm) sizes. For non-mass-like lesions, both modalities showed similar diagnostic performance.Keywords: contrast-enhanced ultrasound, dynamic contrast-enhanced MRI, mass-like breast lesion, non-mass-like breast lesion, breast cancer

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.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.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. HE 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.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.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.

The purpose of this study was to provide a theoretical basis for the evaluation of Angelica quality and soil fertility in three main producing areas of Angelica sinensis and to determine the correlation between endophytic bacteria and bacteria from rhizospheric soil. The diversity of endophytic bacteria from Angelica sinensis root and bacteria from Angelica sinensis rhizospheric soil in three main producing areas (Meichuan town, Huichuan town and Dongjiang town) of Angelica in Gansu Province were examined in this study. A total of 205,536 valid reads were obtained from all the samples by high-throughput sequencing, and 199,637 optimized reads were retained. The Illumina sequencing analysis results showed that the diversity of endophytic bacteria and bacteria in the Angelica sinensis rhizospheric soil of Meichuan was more significant than that of Dongjiang and Huichuan. Venn diagrams and taxonomic composition results showed that some of the endophytic bacteria of Angelica sinensis root were the same as those of rhizospheric soil bacteria, indicating that the endophytic bacteria may have come from rhizospheric soil. Bacterial colonization in the rhizospheric soil of Angelica sinensis may be the main source of endophytic bacteria, and the quality of Angelica sinensis may be closely related to the diversity of its endophytes and the bacteria in the rhizospheric soil.

Our previous study had demonstrated that oral administration of Houttuynia cordata polysaccharides (HCP) without in vitro antiviral activity ameliorated gut and lung injuries induced by influenza A virus (IAV) in mice. However, as macromolecules, HCP was hard to be absorbed in gastrointestinal tract and had no effect on lung injury when administrated intravenously. The action mechanism of HCP was thus proposed as regulating the gut mucosal-associated lymphoid tissue (GALT). Actually, HCP treatment restored the balance of Th17/Treg cells firstly in GALT and finally in the lung. HCP reduced the expression of chemokine CCL20 in the lung and regulated the balance of Th17/Treg carrying CCR6+ (the CCL20 receptor), which was associated with specific migration of Th17/Treg cells from GALT to lung. In vitro, HCP inhibited Th17 cell differentiation through the downregulation of phospho-STAT3, whereas it promoted Treg cell differentiation by upregulating phospho-STAT5. Furthermore, its therapeutic effect was abolished in RORγt-/- or Foxp3-/- mice. These findings indicated that oral administration of macromolecular polysaccharides like HCP might ameliorate lung injury in IAV infected mice via directly regulating the balance of Th17/Treg cells in gut-lung axis. Our results provided a potential mechanism underlying the therapeutic effect of polysaccharides on pulmonary infection.

Based on its inhibition by antagonists, the A

Jiawei Liu,1,* Yan Xu,1,* Muxin Yu,1,* Zhao Liu,1,2,* Yi Xu,3,* Ge Ma,1 Wenbin Zhou,1 Peng Kong,1 Lijun Ling,1 Shui Wang,1 Hong Pan,1 Yi Zhao1 1Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Pan; Yi ZhaoDepartment of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, People’s Republic of ChinaTel/Fax +86-25-83718836Email pamghong@163.com; doctorzhaoyi@sina.cnBackground: Circulating tumor cells (CTCs) intravasate into the bloodstream throughout early cancer stages, promoting metastasis. The tumor microenvironment plays a crucial role in disease progression and outcome. The aim of this prospective study was to investigate the associations of intratumoral and stromal tumor-infiltrating lymphocytes (TILs) with CTCs among patients receiving neoadjuvant chemotherapy (NAC).Methods: We analyzed CTCs in 30 patients with primary breast cancer before and after NAC. The numbers of intratumoral TILs (iTILs) and stromal TILs (sTILs) from pre-NAC formalin-fixed paraffin-embedded core biopsies and post-NAC surgical samples were analyzed. The associations of TILs with pathologic complete response (pCR) and outcome were also evaluated.Results: Of the 30 patients, pCR was achieved in nine (30.0%) patients. A total of 25 (83.3%) patients were CTC-positive before NAC, and eight (26.7%) patients were CTC-positive after NAC. Neither CTC detection before NAC nor CTC after NAC was predictive of pCR. Nevertheless, the presence of CTCs after NAC was significantly associated with early metastatic relapse (P = 0.049) and worse disease-free survival (P = 0.009). After NAC, total sTILs, CD4+ T cells, and CD8+ T cells were significantly correlated with CTC detection. Increased infiltration of sTILs and CD4+ T cells was also an unfavorable prognostic factor as measured by the rate of metastatic relapse.Conclusion: Detection of CTCs after NAC was positively associated with the metastatic relapse of breast cancer patients. Increased infiltration of sTILs after NAC was correlated with CTCs and was found to be an unfavorable prognostic factor.Keywords: circulating tumor cells, tumor infiltrating lymphocytes, neoadjuvant chemotherapy, breast cancer, metastatic relapse

Aims Electroactive micro-organisms play a significant role in microbial fuel cells. It is necessary to discover potential resources in plant endophytes. In this study, plant tissues were selected to isolate endophytic bacteria, and the electrochemical activity potential was evaluated. Methods and results The microbial fuel cell (MFC) is used to evaluate the electricity-producing activity of endophytic bacteria in plant tissues, and the species distribution of micro-organisms in the anode of the MFC after inoculation of plant tissues is determined by high-throughput sequencing. Twenty-six strains of bacteria were isolated from plant tissues belonging to Angelica and Sweet Potato, of which 17 strains from six genera had electrochemical activity, including Bacillus sp., Pleomorphomonas sp., Rahnella sp., Shinella sp., Paenibacillus sp. and Staphylococcus sp. Moreover, the electricity-producing micro-organisms in the plant tissue are enriched. Pseudomonas and Clostridioides are the dominant genera of MFC anode inoculated with angelica tissue. Staphylococcus and Lachnoclostridium are the dominant genera in MFC anode inoculated with sweet potato tissue. And the most representative Gram-positive strain Staphylococcus succinus subsp. succinus H6 and plant tissue were further analysed for electrochemical activity. And a strain numbered H6 and plant tissue had a good electrogenerating activity. Conclusion This study is of great significance for expanding the resource pool of electricity-producing micro-organisms and tapping the potential of plant endophytes for electricity-producing. Significance and Impact of Study This is the first study to apply plant endophytes to MFC to explore the characteristics of electricity production. It is of great significance for exploring the diversity of plant endophytes and the relationship between electricity producing bacteria and plants.

HIV-1 functional cure requires sustained viral suppression without antiretroviral therapy. While effector-memory CD8+ T lymphocytes are essential for viremia control, few vaccines elicit such cellular immunity that could be potently recalled upon viral infection. Here, we investigated a program death-1 (PD1)-based vaccine by fusion of simian immunodeficiency virus capsid antigen to soluble PD1. Homologous vaccinations suppressed setpoint viremia to undetectable levels in vaccinated macaques following a high-dose intravenous challenge by the pathogenic SHIVSF162P3CN. Poly-functional effector-memory CD8+ T cells were not only induced after vaccination, but were also recalled upon viral challenge for viremia control as determined by CD8 depletion. Vaccine-induced effector memory CD8+ subsets displayed high cytotoxicity-related genes by single-cell analysis. Vaccinees with sustained viremia suppression for over two years responded to boost vaccination without viral rebound. These results demonstrated that PD1-based vaccine-induced effector-memory CD8+ T cells were recalled by AIDS virus infection, providing a potential immunotherapy for functional cure., Author summary HIV-1/AIDS remains a major global pandemic although treatment regimen has improved. Identifying efficacious vaccines and therapeutics to achieve long-term viral control with very low/undetectable plasma viral loads in the absence of antiretroviral therapy, a status known as functional cure, would be highly beneficial. We previously demonstrated that antigens fused to a soluble program death-1 (PD1) domain could effectively bind and be cross-presented by dendritic cells that constitutively expressed PD1 ligands. When applied in the form of DNA vaccination, this antigen-targeting strategy was highly immunogenic in mice. Here, we investigated the efficacy of the PD1-based DNA vaccine approach against pathogenic simian-human immunodeficiency virus challenge in rhesus monkeys. Our results showed that homologous PD1-based DNA vaccinations induced highly functional effector-memory CD8+ T cells carrying a unique cytotoxicity gene expression profile. These T cells actively supressed viremia in monkeys and were re-activated via boost vaccination at 2 years after viral challenge without viral rebound. In summary, our study demonstrates the potential application of PD1-based DNA vaccination to control AIDS virus infection.

Seven endophytic yeast strains were isolated from tangerine peel (Citrus reticulata Blanco) and genotyped through clustering with D1/D2 and ITS1-5.8S-ITS2 sequences from GenBank. Phenotypic characteristics were obtained through commercial kits and through assisted species identification. Indole-3-acetic acid (IAA) production by the yeast strains was assessed using Salkowski reagent and High-Performance Liquid chromatography (HPLC). The growth-promoting effects of the yeast were evaluated using the 'ragdoll' method. CRYb1, CRYb2 and CRYb7 isolates were identified as the closest species Hanseniaspora opuntiae. CRYb3 was identified as Pichia kluyveri. CRYb4, CRYb5 and CRYb6 were identified as Meyerozyma guilliermondii. CRYb1, CRYb5, CRYb6 and CRYb7 were found to be capable of IAA production. The most promising yeast strains now require further evaluation for their ability to promote plant growth in vitro and in vivo. These data increase our knowledge of the distribution and biological properties of endophytic yeast. This is important information that will be required to fully harness the growth-promoting properties of yeast strains.

Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg−1(d−1. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.

Background Many elderly breast cancer patients might just receive palliative local surgery, especially those with locally advanced breast cancer (LABC). However, palliative tumor removal might lead to perioperative residual tumor growth. In this study, we aimed to determine the survival effect of palliative local surgery without definitive axillary surgery for LABC in elderly patients. Patients and Methods Patients age 70 years or older diagnosed with T3/4M0 breast cancer, who received no surgery, mastectomy, or lumpectomy without axillary surgery, were identified in the Surveillance, Epidemiology, and End Results cancer database from 1973 to 2014. The overall survival effect of palliative local surgery was determined by using multivariable Cox regression, and propensity score matching was applied to confirm the results. Results A total of 2616 female breast cancer patients age 70 years or older diagnosed with T3/4M0 (without inflammatory breast cancer) were identified; 1374 received no cancer-directed surgery, 583 received lumpectomy without axillary surgery, and 659 received mastectomy without axillary surgery. Adjusted for potential confounders, both types of palliative local surgeries (lumpectomy: hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.71-1.27; P = .719; mastectomy: HR, 0.88; 95% CI, 0.65-1.17; P = .371) were not associated with overall survival compared with no surgery within hormone receptor-positive patients. However, mastectomy strongly improved survival within hormone receptor-negative patients. Palliative local surgery did not change the patterns of mortality. Conclusion For elderly patients diagnosed with LABC, not candidates for standard therapies, mastectomy should be recommended as palliative therapy for hormone receptor-negative, but not for hormone receptor-positive patients.

Humanized mice have become useful animal models for HIV/AIDS. Since NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ (NSG) mice allow the engraftment of primary human immune cells, we aim to determine the role of human Fms-related tyrosine kinase 3 ligand (hFlt3L), a major growth factor for dendritic cells (DCs), in regulating the differentiation of cord blood-derived CD34+ progenitor cells in this murine species. Soluble recombinant hFlt3L protein and AAV-vectored hFlt3L were administrated before or after human CD34+ progenitor cell transplantation, respectively. We then measured the peripheral levels of hFlt3L by ELISA. Meantime, reconstituted human immune cells were analyzed by flow cytometry over time. We found that without hFlt3L there were significantly increased types of human immune cells in NSG-huCD34 compared with NSG-huPBL mice but the frequency of human DCs remains low. Transient treatment with recombinant hFlt3L expanded human conventional CD1c+ and CD141+ DCs as well as plasmacytoid DCs in humanized NSG-huCD34 mice. Surprisingly, however, the prolonged in vivo expression of AAV-vectored hFlt3L resulted in significant suppression of total human CD34+ cell engraftment and differentiation. The suppression occurred within 2 weeks when AAV-vectored hFlt3L was administered either before or after the transplantation of CD34+ progenitor cells, which was likely associated with the induction of murine myeloid-derived immune suppressive cells and reactive oxygen species in NSG-huCD34 mice. Since chronic HIV-1 patients displayed significantly high levels of hFlt3L expression, our findings may have implication to explore the role of prolonged hFlt3L in regulating the differentiation of human CD34+ progenitor cells in both NSG-huCD34 mice and infected people.

Background Infections induced by influenza viruses, as well as coronavirus disease 19 (COVID-19) pandemic induced by severe acute respiratory coronavirus 2 (SARS-CoV-2) led to acute lung injury (ALI) and multi organ failure, during which traditional Chinese medicine (TCM) played an important role in treatment of the pandemic. The study aimed to investigate the effect of Indigo Naturalis on ALI induced by influenza A virus (IAV) in mice. Method The anti-influenza and anti-inflammatory properties of aqueous extract of Indigo Naturalis (INAE) were evaluated in vitro. BALB/c mice inoculated intranasally with IAV (H1N1) were treated intragastrically with INAE (40, 80 and 160 mg/kg/day) 2 h later for 4 or 7 days. Animal lifespan and mortality were recorded. Expression of high mobility group box-1 protein (HMGB-1) and toll-like receptor 4 (TLR4) were evaluated through immunohistological staining. Inflammatory cytokines were also monitored by ELISA. Result INAE inhibited virus replication on Madin-Darby canine kidney (MDCK) cells and decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated peritoneal macrophages in vitro. The results showed that oral administration of 160 mg/kg of INAE significantly improved the lifespan (P P P P P P P P Conclusion The results showed that INAE alleviated IAV induced ALI in mice. The mechanisms of INAE were associated with its anti-influenza, anti-inflammatory and anti-oxidation properties. Indigo Naturalis might have clinical potential to treat ALI induced by IAV.

Electroactive microorganisms play a significant role in microbial fuel cells (MFCs). These devices, which are based on a wide microbial diversity, can convert a large array of organic matter components into sustainable and renewable energy. At present, electricity-producing microorganisms are mostly isolated from sewage, anaerobic sediments and soil, however, the sources are very limited. For a more comprehensive understanding of the electron transfer mechanism of the electricity-producing microorganisms and the interaction with the environment, it is necessary to obtain a thorough understanding of their resource distribution and discover potential resources. In this study, plant 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. Twenty-six strains of endophytic bacteria were isolated from plant tissues belonging to Angelica and Sweet Potato, of which 17 strains from 6 genera had electrochemical activity, including Bacillus sp., Pleomorphomonas sp., Rahnella sp., Shinella sp., Paenibacillus sp. and Staphylococcus sp.. Moreover, the electricity-producing microorganisms in the plant tissue are enriched. Microbial community analysis by high-throughput sequence indicated that Pseudomonas and Clostridioides are the dominant genera of MFC anode inoculated with angelica tissue.Staphylococcus and Lachnoclostridium 5 are the dominant genera in MFC anode inoculated with sweet potato tissue. And the most representative Gram-positive strain Staphylococcus succinus subsp. succinus H6 and plant tissue-inoculated MFC were further analyzed for electrochemical activity. After nearly 1500 h of voltage monitoring and cyclic voltammetry analysis, the results showed that a strain numbered H6 and plant tissue-inoculated MFC had a good electrogenerating activity.ImportanceSome biological characteristics of microorganisms are inextricably linked to their living environment. For plant endophytes, some of their biological characteristics have a profound impact on the host. The discovery of the production of electrobacteria in plants helps us to understand the interaction between microorganisms and plants more deeply. For example, there may be intercellular electron transfer between the internally producing bacteria and nitrogen-fixing bacteria to improve the efficiency of nitrogen fixation. In addition, there may be a connection between the weak electrical signal of the plant and the the endophytic electricity-producing microorganismsThe discovery of electricity-producing bacteria in plants also brings a more comprehensive understanding of the distribution of electricity-producing microbial resources and the mechanism of origin.

Although progress has been made on constructing potent bi-specific broadly neutralizing antibody (bi-bNAb), few bi-bNAbs have been evaluated against HIV-1/AIDS in non-human primates (NHPs). Here, we report the efficacy of a tandem bi-bNAb, namely BiIA-SG, in Chinese-origin rhesus macaques (CRM) against the CRM-adapted R5-tropic pathogenic SHIV