Effector Cs02526 from Ciboria shiraiana induces cell death and modulates plant immunity.

Sclerotinia disease is one of the most devastating fungal diseases worldwide, as it reduces the yields of many economically important crops. Pathogen-secreted effectors play crucial roles in infection processes. However, key effectors of Ciboria shiraiana, the pathogen primarily responsible for sclerotinia disease in mulberry (Morus spp.), remain poorly understood. In this study, we identified and functionally characterized the effector Cs02526 in C. shiraiana and found that Cs02526 could induce cell deathin a variety of plants. Moreover, Cs02526-induced cell death was mediated by the central immune regulator BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1 (BAK1), dependent on a 67-amino acid fragment. Notably, Cs02526 homologues were widely distributed in hemibiotrophic and necrotrophic phytopathogenic fungi, but the homologues failed to induce cell death in plants. Pre-treatment of plants with recombinant Cs02526 protein enhanced resistance against both C. shiraiana and Sclerotinia sclerotiorum. Furthermore, the pathogenicity of C. shiraiana was diminished upon spraying plants with synthetic dsRNA-Cs02526. In conclusion, our findings highlight the cell death-inducing effector Cs02526 as a potential target for future biological control strategies against plant diseases.

Efficacy and safety of inactivated SARS-CoV-2 vaccination in COVID-19-associated pneumonia among patients with rheumatic and musculoskeletal diseases: A real-world retrospective observational study.

OBJECTIVES: To identify the effectiveness and safety of inactivated SARS-CoV-2 vaccines in rheumatic and musculoskeletal diseases (RMDs) patients. METHODS: RMD patients with COVID-19 in Jiangsu Province were polled between December 8, 2022, and February 1, 2023. Information on demographics, disease characteristics, antirheumatic drug use, vaccination status and survival state were collected. COVID-19-associated pneumonia was the primary outcome. The effect of COVID-19 immunization on RMD patients was assessed using multivariate logistic regression, and the adverse events (AEs) following vaccination were evaluated. RESULTS: Among 592 RMD patients with COVID-19, 276 (46.6%) individuals experienced COVID-19-associated pneumonia, and 290 (49.0%) patients were injected with inactivated vaccines. In multivariate logistic regression analysis, vaccines reduced the incidence of COVID-19-associated pneumonia, and receiving booster vaccine was an independent protective factor for COVID-19-associated pneumonia in RMD patients (OR 0.64, 95% CI 0.41-0.98, p = .034). In particular, inactivated vaccines have a protective impact on RMD patients with a high risk of developing pneumonia, including those aged 45 years and older (OR 0.53, 95% CI 0.34-0.83), and who have lung involvement (OR 0.43, 95% CI 0.23-0.82). The total AEs rate of vaccines was 13.9% (40/290), only 11 (3.8%) experienced the recurrence or deterioration of RMDs, and no serious AEs occurred. CONCLUSION: Inactivated COVID-19 vaccines were safe and effective in reducing the risk of COVID-19-associated pneumonia of RMD patients in China.

Integrating serum pharmacochemistry and network pharmacology to explore potential compounds and mechanisms of Alpiniae oxyphyllae fructus in the treatment of cellular senescence in diabetic kidney disease.

Background: Diabetic kidney disease (DKD), one of the microvascular complications in patients with diabetes mellitus, is a common cause of end-stage renal disease. Cellular senescence is believed to be an essential participant in the pathogenesis of DKD. Although there is evidence that Alpiniae oxyphyllae fructus (AOF) can ameliorate DKD progression and organismal senescence, its ability to ameliorate renal cellular senescence in DKD as well as active components and molecular mechanisms remain to be explored. Purpose: This study aimed to investigate the role of AOF in the treatment of cellular senescence in DKD and to explore its active components and potential molecular mechanisms. Methods: The pharmacological efficacy of AOF in ameliorating cellular senescence in DKD was assessed by establishing DKD mouse models and HK-2 cells under high glucose stress. UHPLC-QTOF-MS was used to screen the active compounds in AOF, which were used in conjunction with network pharmacology to predict the molecular mechanism of AOF in the treatment of cellular senescence in DKD. Results: In vivo experiments showed that AOF reduced GLU, mAlb, Scr, BUN, MDA, SOD levels, and ameliorated renal pathological damage and renal cell senescence in DKD mice. In vitro experiments showed that AOF-containing serum improved the decline in HK-2 cell viability and alleviated cellular senescence under high glucose intervention. The results of the UHPLC-QTOF-MS screened 26 active compounds of AOF. The network pharmacological analyses revealed that Cubebin, 2',6'-dihydroxy-4'-methoxydihydrochalcone, Chalcone base + 3O,1Prenyl, Batatasin IV, and Lucidenolactone were the five core compounds and TP53, SRC, STAT3, PIK3CA, and AKT1 are the five core targets of AOF in the treatment of DKD. Molecular docking simulation results showed that the five core compounds had good binding ability to the five core targets. Western blot validated the network pharmacological prediction results and showed that AOF and AOF-containing serum down-regulate the expression of TP53, and phosphorylation of SRC, STAT3, PIK3CA, and AKT. Conclusion: Our study shows that AOF may delay the development of cellular senescence in DKD by down-regulating the levels of TP53, and phosphorylation of SRC, STAT3, PIK3CA, and AKT.

Efficacy and safety of culture-expanded mesenchymal stromal cell therapy in the treatment of 4 types of inflammatory arthritis: A systematic review and meta-analysis of 36 randomized controlled trials.

OBJECTIVE: This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in the treatment of inflammatory arthritis. METHODS: Two researchers conducted a comprehensive search of Chinese and English databases from their inception until July 2023. The literature screening and data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software. RESULTS: A total of 36 relevant RCTs, involving 2,076 participants, were ultimately included in this study. These RCTs encompassed four types of inflammatory arthritis, namely rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and systemic sclerosis (SSc). The results demonstrated that MSC therapy exhibited improvements in the Visual Analog Scale (VAS) for pain in OA patients (bone marrow: SMD=-0.95, 95 % CI: -1.55 to -0.36, P = 0.002; umbilical cord: SMD=-2.03, 95 % CI: -2.99 to -1.07, P < 0.0001; adipose tissue: SMD=-1.26, 95 % CI: -1.99 to -0.52, P = 0.0009). Specifically, MSCs sourced from adipose tissue showed enhancements in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (P = 0.0001), WOMAC physical function (P = 0.001), and total WOMAC scores (P = 0.0003). As for MSC therapy in RA, AS, and SSc, the current systematic review suggests a potential therapeutic effect of MSCs on these inflammatory arthritic conditions. Safety assessments indicated that MSC therapy did not increase the incidence of adverse events. CONCLUSION: MSCs have the potential to alleviate joint pain and improve joint function in patients with inflammatory arthritis. Moreover, MSC therapy appears to be relatively safe and could be considered as a viable alternative treatment option for inflammatory arthritis.

High-power electrically pumped terahertz topological laser based on a surface metallic Dirac-vortex cavity.

Topological lasers (TLs) have attracted widespread attention due to their mode robustness against perturbations or defects. Among them, electrically pumped TLs have gained extensive research interest due to their advantages of compact size and easy integration. Nevertheless, limited studies on electrically pumped TLs have been reported in the terahertz (THz) and telecom wavelength ranges with relatively low output powers, causing a wide gap between practical applications. Here, we introduce a surface metallic Dirac-vortex cavity (SMDC) design to solve the difficulty of increasing power for electrically pumped TLs in the THz spectral range. Due to the strong coupling between the SMDC and the active region, robust 2D topological defect lasing modes are obtained. More importantly, enough gain and large radiative efficiency provided by the SMDC bring in the increase of the output power to a maximum peak power of 150 mW which demonstrates the practical application potential of electrically pumped TLs.

High brightness terahertz quantum cascade laser with near-diffraction-limited Gaussian beam.

High-power terahertz (THz) quantum cascade laser, as an emerging THz solid-state radiation source, is attracting attention for numerous applications including medicine, sensing, and communication. However, due to the sub-wavelength confinement of the waveguide structure, direct beam brightness upscaling with device area remains elusive due to several mode competition and external optical lens is normally used to enhance the THz beam brightness. Here, we propose a metallic THz photonic crystal resonator with a phase-engineered design for single mode surface emission over a broad area. The quantum cascade surface-emitting laser is capable of delivering an output peak power over 185 mW with a narrow beam divergence of 4.4° × 4.4° at 3.88 THz. A high beam brightness of 1.6 × 107 W sr-1m-2 with near-diffraction-limited M2 factors of 1.4 in both vertical and lateral directions is achieved from a large device area of 1.6 × 1.6 mm2 without using any optical lenses. The adjustable phase shift between the lattices enables a stable and high-intensity surface emission over a broad device area, which makes it an ideal light extractor for large-scale THz emitters. Our research paves the way to high brightness solid-state THz lasers and facilitates new applications in standoff THz imaging, detection, and diagnosis.