Plant diseases caused by fungi and oomycetes pose an increasing threat to food security and ecosystem health worldwide. These filamentous pathogens, while taxonomically distinct, modulate host defense responses by secreting effectors, which are typically identified based on the presence of signal peptides. Here we show that Phytophthora sojae and Verticillium dahliae secrete isochorismatases (PsIsc1 and VdIsc1, respectively) that are required for full pathogenesis. PsIsc1 and VdIsc1 can suppress salicylate-mediated innate immunity in planta and hydrolyse isochorismate in vitro. A conserved triad of catalytic residues is essential for both functions. Thus, the two proteins are isochorismatase effectors that disrupt the plant salicylate metabolism pathway by suppressing its precursor. Furthermore, these proteins lack signal peptides, but exhibit characteristics that lead to unconventional secretion. Therefore, this secretion pathway is a novel mechanism for delivering effectors and might play an important role in host–pathogen interactions.
Deciphering the dynamic changes in antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. Here we analyze the laboratory findings of 1,850 patients to describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)-specific immunoglobulin M (IgM) and G (IgG) levels during SARS-CoV-2 infection and recovery. The generation of S-, RBD-, and N-specific IgG occurs one week later in patients with severe/critical COVID-19 compared to patients with mild/moderate disease, while S- and RBD-specific IgG levels are 1.5-fold higher in severe/critical patients during hospitalization. The RBD-specific IgG levels are 4-fold higher in older patients than in younger patients during hospitalization. In addition, the S- and RBD-specific IgG levels are 2-fold higher in the recovered patients who are SARS-CoV-2 RNA negative than those who are RNA positive. Lower S-, RBD-, and N-specific IgG levels are associated with a lower lymphocyte percentage, higher neutrophil percentage, and a longer duration of viral shedding. Patients with low antibody levels on discharge might thereby have a high chance of being tested positive for SARS-CoV-2 RNA after recovery. Our study provides important information for COVID-19 diagnosis, treatment, and vaccine development.
Coronavirus disease 2019 (COVID-19) is causing worldwide pandemic with no specific therapeutic agents, especially for severe or critical patients. To comprehensively evaluate the effectiveness, safety, and indications of convalescent plasma transfusion (CPT) therapy for severe or critical COVID-19 patients, we analyzed the clinical, laboratory, and radiologic characteristics of 1,568 patients from a single center, in which 138 patients received ABO-compatible CPT. The median time from the first symptom to CPT was 45 days. 2.2% and 4.1% of cases died in the CPT group and in the standard-treatment group, respectively. 2.4% and 5.1% of patients in the CPT and the standard-treatment group have been admitted to ICU eventually. 70% of the patients who had severe respiratory symptoms got improved and removed oxygen supports within 7 days after CPT. The viral loads and C-reactive protein (CRP) concentration significantly decreased (P<0.001), and the percentage of lymphocytes increased (P=0.006), 76.8% of cases received radiological improvements within 14 days after CPT. Patients with a higher percentage of lymphocytes and a lower percentage of neutrophils and CRP concentration respond better to CPT (P<0.05). Notably, for the patients who received CPT within 7 weeks after symptom onset, the median time from CPT to clinical improvements was approximately 10 days. But the time to clinical improvements was significantly prolonged for patients who received CPT later than 7 weeks after onset. Our study will provide important information for the clinical practice in COVID-19 treatment, as well as provide real-world observations and clinical data for the development of monoclonal antibodies.
Microalgae, a naturally present unicellular microorganism, can undergo light photosynthesis and have been used in biofuels, nutrition, etc. Here, we report that engineered live microalgae can be delivered to hypoxic tumor regions to increase local oxygen levels and resensitize resistant cancer cells to both radio- and phototherapies. We demonstrate that the hypoxic environment in tumors is markedly improved by in situ–generated oxygen through microalgae-mediated photosynthesis, resulting in notably radiotherapeutic efficacy. Furthermore, the chlorophyll from microalgae produces reactive oxygen species during laser irradiation, further augmenting the photosensitizing effect and enhancing tumor cell apoptosis. Thus, the sequential combination of oxygen-generating algae system with radio- and phototherapies has the potential to create an innovative treatment strategy to improve the outcome of cancer management. Together, our findings demonstrate a novel approach that leverages the products of photosynthesis for treatment of tumors and provide proof-of-concept evidence for future development of algae-enhanced radio- and photodynamic therapy.
Biohybrid microswimmers have recently shown to be able to actively perform in targeted delivery and in vitro biomedical applications. However, more envisioned functionalities of the microswimmers aimed at in vivo treatments are still challenging. A photosynthetic biohybrid nanoswimmers system (PBNs), magnetic engineered bacteria-Spirulina platensis, is utilized for tumor-targeted imaging and therapy. The engineered PBNs is fabricated by superparamagnetic magnetite (Fe 3 O 4 NPs) via a dip-coating process, enabling its tumor targeting ability and magnetic resonance imaging property after intravenous injection. It is found that the PBNs can be used as oxygenerator for in situ O 2 generations in hypoxic solid tumors through photosynthesis, modulating the tumor microenvironment (TME), thus improving the effectiveness of radiotherapy (RT). Furthermore, the innate chlorophyll released from the RT-treated PBNs, as a photosensitizer, can produce cytotoxic reactive oxygen species under laser irradiation to achieve photodynamic therapy. Excellent tumor inhibition can be realized by the combined multimodal therapies. The PBNs also possesses capacities of chlorophyll-based fluorescence and photoacoustic imaging, which can monitor the tumor therapy and tumor TME environment. These intriguing properties of the PBNs provide a promising microrobotic platform for TME hypoxic modulation and cancer theranostic applications.
Due to the inability to spontaneously heal and vulnerability to bacterial infection, diabetic patients are frustrated by unexpected epithelium injuries in daily life. Notably, a drug-resistant bacterial infection may result in a long-term impact to the natural function of damaged organs. It is imperative to develop strategies that promote injury recovery and eradicate drug-resistant infection simultaneously. Here, we present a composite structured cupriferous hollow nanoshell (AuAgCu2O NS) that consists of a hollow gold–silver (AuAg) core and Cu2O shell as a photothermal therapeutic agent for a cutaneous chronic wound and nonhealing keratitis with drug-resistant bacterial infection. The controllable photothermal therapeutic effect and released silver ion from the hollow AuAg core possess a synergistic effect to eradicate multi-drug-resistant bacteria, including extended-spectrum β-lactamase Escherichia coli (ESBL E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). Meanwhile, the released copper ion from the Cu2O shell could expedite endothelial cell angiogenesis and fibroblast cell migration, thus boosting wound-healing effects. In both infection-complicated disease models, the ophthalmic clinical score, wound closure rates, and histopathology analysis demonstrate that the AuAgCu2O NSs could facilitate the re-epithelialization at the wound area and eliminate the complicated bacterial infection from diabetic mice. A primary signal path involved in the promoted healing effect was further illustrated by comprehensive assays of immunohistochemical evaluation, Western blot, and quantitative polymerase chain reaction. Taken together, our AuAgCu2O NSs are shown to be potent candidates for clinical utilization in the treatment of diabetic epithelium injuries.
Oomycete pathogens produce a large number of CRN effectors to manipulate plant immune responses and promote infection. However, their functional mechanisms are largely unknown. Here, we identified a Phytophthora sojae CRN effector PsCRN108 which contains a putative DNA-binding helix-hairpin-helix (HhH) motif and acts in the plant cell nucleus. Silencing of the PsCRN108 gene reduced P. sojae virulence to soybean, while expression of the gene in Nicotiana benthamiana and Arabidopsis thaliana enhanced plant susceptibility to P. capsici. Moreover, PsCRN108 could inhibit expression of HSP genes in A. thaliana, N. benthamiana and soybean. Both the HhH motif and nuclear localization signal of this effector were required for its contribution to virulence and its suppression of HSP gene expression. Furthermore, we found that PsCRN108 targeted HSP promoters in an HSE- and HhH motif-dependent manner. PsCRN108 could inhibit the association of the HSE with the plant heat shock transcription factor AtHsfA1a, which initializes HSP gene expression in response to stress. Therefore, our data support a role for PsCRN108 as a nucleomodulin in down-regulating the expression of plant defense-related genes by directly targeting specific plant promoters.
In article number 1910395, Min Zhou and co‐workers utilize a photosynthetic biohybrid nanoswimmer system (PBNs), comprising magnetically engineered Spirulina platensis, for tumor‐targeted imaging and therapy. The PBNs can be used as oxygenerators for in situ O2 generation in hypoxic solid tumors through photosynthesis, thus modulating the tumor microenvironment and improving the effectiveness of radiotherapy.
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