Two typical acyl-CoA-binding proteins (ACBPs) are required for the asexual development and virulence of Phytophthora sojae.

Being found in all eukaryotes investigated, acyl-CoA-binding proteins (ACBPs) participate in lipid metabolism via specifically binding acyl-CoA esters with high affinity. The structures and functions of ACBP family proteins have been extensively described in yeasts, fungi, plants and mammals, but not oomycetes. In the present study, seven ACBP genes named PsACBP1-7 were identified from the genome of Phytophthora sojae, an oomycete pathogen of soybean. CRISPR-Cas9 knockout mutants targeting PsACBP1 and PsACBP2 were created for phenotypic assays. PsACBP1 knockout led to defects in sporangia production and virulence. PsACBP2 knockout mutants exhibited impaired vegetative growth, zoospore production, cyst germination and virulence. Moreover, Nile red staining of PsACBP2 knockout and over-expression lines showed that PsACBP2 is involved in the formation of lipid bodies in P. sojae. Our results demonstrate that two ACBP genes are differently required for growth and development, and both are essential for virulence in P. sojae.

Double-faced role of Bcl-2-associated athanogene 7 in plant-Phytophthora interaction.

Due to their sessile nature, plants must respond to various environmental assaults in a coordinated manner. The endoplasmic reticulum is a central hub for plant responses to various stresses. We previously showed that Phytophthora utilizes effector PsAvh262-mediated binding immunoglobulin protein (BiP) accumulation for suppressing endoplasmic reticulum stress-triggered cell death. As a BiP binding partner, Bcl-2-associated athanogene 7 (BAG7) plays a crucial role in the maintenance of the unfolded protein response, but little is known about its role in plant immunity. In this work, we reveal a double-faced role of BAG7 in Arabidopsis-Phytophthora interaction in which it regulates endoplasmic reticulum stress-mediated immunity oppositely in different cellular compartments. In detail, it acts as a susceptibility factor in the endoplasmic reticulum, but plays a resistance role in the nucleus against Phytophthora. Phytophthora infection triggers the endoplasmic reticulum-to-nucleus translocation of BAG7, the same as abiotic heat stress; however, this process can be prevented by PsAvh262-mediated BiP accumulation. Moreover, the immunoglobulin/albumin-binding domain in PsAvh262 is essential for both pathogen virulence and BiP accumulation. Taken together, our study uncovers a double-faced role of BAG7; Phytophthora advances its colonization in planta by utilizing an effector to detain BAG7 in the endoplasmic reticulum.

Identification of nitroimidazole-oxime derivatives targeting the polo-box domain of polo-like kinase 1.

Recent progress in the development of small molecular skeleton-derived polo-like kinase (PLK1) catalytic domain (KD) inhibitors has led to the synthesis of multiple ligands with high binding affinity. However, few systematic analyses have been conducted to identify key PLK1-PBD domain and characterize their interactions with potent PLK1 inhibitors. Therefore, we designed a series of PLK1-PBD inhibitors with an in silico scaffold modification strategy. A docking simulation combined with a primary screen in vitro were performed to filter for the lead compound, which was then substituted, synthesized and evaluated by a variety of bioassays. The biological profile of 4v suggests that this compound may be developed as a potential anticancer agent.

Case report: A rare case of simultaneous necrotizing fasciitis of the breast and forearm.

Necrotizing fasciitis is an aggressive bacterial infection that causes necrosis of the fascia and subcutaneous tissues with rapid progression and high mortality. Early stages often lead to misdiagnosis, resulting in improper treatment and severe implications. This case study presents a patient with diabetes mellitus combined with hepatitis B who rapidly developed necrotizing fasciitis of the left forearm and left breast after trauma and controlled the infection with early surgical treatment. It is worth noting that early surgical exploration is the gold standard for the diagnosis of necrotizing fasciitis and is the most effective means of reducing mortality and amputation rates in necrotizing fasciitis.

Self-Healing Photothermal Nanotherapeutics for Enhanced Tumor Therapy through Triple Ferroptosis Amplification and Cascade Inflammation Inhibition.

The therapeutic effectiveness of photothermal therapy (PTT) is limited by heat tolerance and PTT-induced inflammation, which increases the risk of tumor metastasis and recurrence. Ferroptosis combined with PTT can achieve significant therapeutic effects. In this work, we designed self-healing photothermal nanotherapeutics to achieve effective PTT with triple-amplified ferroptosis and cascade inflammation inhibition after photothermal treatment. After the ferroptosis-inducing ability of mangiferin (MF) was first elucidated, the nanocomplex PFeM, coordinated by Fe3+ and MF with polyvinylpyrrolidone (PVP) modification, was prepared by a one-pot self-assembly method. PFeM with laser irradiation could induce intensified ferroptosis by integrating the functions of MF to deactivate glutathione peroxidase 4, Fe3+/Fe2+ to generate lethal reactive oxygen species via the Fenton reaction, and the photothermal effect to amplify ferroptosis. More importantly, the released MF could achieve cascade inflammation inhibition, thereby reversing the proinflammatory microenvironment caused by PTT. The in vivo antitumor and anti-inflammatory effects of PFeM were further confirmed in a 4T1 tumor-bearing mouse model. This study expounding the ferroptosis-inducing effects of MF and utilizing the strategy of chelating MF with iron ions can provide a new idea for developing photothermal nanoagents with clinically convertible safety ingredients and a green preparation process that improve efficacy and reduce adverse reactions during PTT.

Vaccination and risky behaviors: evidence from the hepatitis B vaccination campaign in China.

Understanding the causal relationship between vaccination and individuals' risky behavioral responses has important policy implications as it affects the ultimate effectiveness of increasing access to vaccination. This paper examines the causal effects of vaccination on risky behaviors by exploring the 1992 hepatitis B vaccination campaign in China. Our empirical strategy exploits variations in age at the campaign as well as the pretreatment infection risks across provinces. Using a large cross-section of individuals born between 1981 and 1994, we find that more exposure to the hepatitis B vaccination leads to lower alcohol use during adulthood, and such impacts are almost entirely driven by men. Individuals from more educated families and people who live in urban areas tend to react more. Improved educational attainment and dissemination of related knowledge are important contributors. Our results uncover an unexpected benefit of promoting access to vaccination. Supplementary Information: The online version contains supplementary material available at 10.1007/s00148-023-00942-4.

A Phytophthora receptor-like kinase regulates oospore development and can activate pattern-triggered plant immunity.

Plant cell-surface leucine-rich repeat receptor-like kinases (LRR-RLKs) and receptor-like proteins (LRR-RLPs) form dynamic complexes to receive a variety of extracellular signals. LRR-RLKs are also widespread in oomycete pathogens, whereas it remains enigmatic whether plant and oomycete LRR-RLKs could mediate cell-to-cell communications between pathogen and host. Here, we report that an LRR-RLK from the soybean root and stem rot pathogen Phytophthora sojae, PsRLK6, can activate typical pattern-triggered immunity in host soybean and nonhost tomato and Nicotiana benthamiana plants. PsRLK6 homologs are conserved in oomycetes and also exhibit immunity-inducing activity. A small region (LRR5-6) in the extracellular domain of PsRLK6 is sufficient to activate BAK1- and SOBIR1-dependent immune responses, suggesting that PsRLK6 is likely recognized by a plant LRR-RLP. Moreover, PsRLK6 is shown to be up-regulated during oospore maturation and essential for the oospore development of P. sojae. Our data provide a novel type of microbe-associated molecular pattern that functions in the sexual reproduction of oomycete, and a scenario in which a pathogen LRR-RLK could be sensed by a plant LRR-RLP to mount plant immunity.

The oomycete-specific BAG subfamily maintains protein homeostasis and promotes pathogenicity in an atypical HSP70-independent manner.

Protein homeostasis is vital for organisms and requires chaperones like the conserved Bcl-2-associated athanogene (BAG) co-chaperones that bind to the heat shock protein 70 (HSP70) through their C-terminal BAG domain (BD). Here, we show an unconventional BAG subfamily exclusively found in oomycetes. Oomycete BAGs feature an atypical N-terminal BD with a short and oomycete-specific α1 helix (α1'), plus a C-terminal small heat shock protein (sHSP) domain. In oomycete pathogen Phytophthora sojae, both BD-α1' and sHSP domains are required for P. sojae BAG (PsBAG) function in cyst germination, pathogenicity, and unfolded protein response assisting in 26S proteasome-mediated degradation of misfolded proteins. PsBAGs form homo- and heterodimers through their unique BD-α1' to function properly, with no recruitment of HSP70s to form the common BAG-HSP70 complex found in other eukaryotes. Our study highlights an oomycete-exclusive protein homeostasis mechanism mediated by atypical BAGs, which provides a potential target for oomycete disease control.

Caizhixuan hair tonic regulates both apoptosis and the PI3K/Akt pathway to treat androgenetic alopecia.

PURPOSE: Caizhixuan hair tonic (CZX) is a topical traditional Chinese medicine (TCM) preparation for the treatment of androgenetic alopecia (AGA). However, its active compounds and underlying mechanism for treating AGA are still unclear. The purpose of this study was to observe the effects of CZX on hair growth promotion in AGA mice and to explore the active components and mechanism. METHODS: Testosterone propionate was administered subcutaneously to mice to establish an AGA mouse model. The therapeutic effects of CZX on AGA were evaluated by observing skin colour changes, hair growth time, and average hair length; calculating the hair growth score; and performing skin histopathological analysis. Following that, CZX chemical components were analysed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Network pharmacology was used to predict the major effects and possible mechanisms of CZX for the treatment of AGA. Furthermore, RT-qPCR and Western blotting were performed to assess the expression of key genes and proteins involved in PI3K/Akt and apoptosis pathways in order to validate CZX's predicted mechanism in AGA. RESULTS: CZX promoted hair growth and improved the pathological morphology of hair follicles in the skin. In UPLC-Q-TOF/MS analysis, 69 components from CZX were isolated. Based on network pharmacology, CZX alleviated AGA by regulating PI3K/Akt and apoptosis pathways. According to RT-qPCR and Western blotting, CZX upregulated the expressions of PI3K, Akt, and Bcl-2, while downregulating that of Bax and caspase-3. CONCLUSIONS: CZX promotes hair growth to treat AGA by regulating the PI3K/Akt and apoptosis pathways.

PsGRASP, a Golgi Reassembly Stacking Protein in Phytophthora sojae, Is Required for Mycelial Growth, Stress Responses, and Plant Infection.

Golgi reassembly stacking proteins (GRASPs) play important roles in Golgi structure formation, ER stress response, and unconventional secretion in eukaryotic cells. However, GRASP functions in oomycetes haven't been adequately characterized. Here, we report the identification and functional analysis of PsGRASP, a GRASP-encoding gene from the soybean-infecting oomycete Phytophthora sojae. Transcriptional profiling showed that PsGRASP expression is up-regulated at the infection stages. PsGRASP knockout mutants were created using the CRISPR/Cas9 system. These mutants exhibited impaired vegetative growth, zoospore release and virulence. PsGRASP was involved ER stress responses and altered laccase activity. Our work suggests that PsGRASP is crucial for P. sojae development and pathogenicity.

Phytophthora sojae leucine-rich repeat receptor-like kinases: diverse and essential roles in development and pathogenicity.

Leucine-rich repeat receptor-like kinases (LRR-RLKs) are critical signal receptors in plant development and defense. Like plants, oomycete pathogen genomes also harbor LRR-RLKs, but their functions remain largely unknown. Here, we systematically characterize all the 24 LRR-RLK genes (PsRLKs) from Phytophthora sojae, which is a model of oomycete pathogens. Although none of them was required for vegetative growth, the specific PsRLKs are important for stress responses, zoospore production, zoospores chemotaxis, and pathogenicity. Interestingly, the Gα subunit PsGPA1 interacts with the five chemotaxis-related PsRLKs via their intracellular kinase domains, and expression of PsGPA1 gene is downregulated in the three mutants (ΔPsRLK17/22/24). Moreover, we generated the PsRLK-PsRLK interaction network of P. sojae and found that PsRLK21, together with PsRLK10 or PsRLK17, regulate virulence by direct association. Taken together, our results reveal the diverse roles of LRR-RLKs in modulating P. sojae development, interaction with soybean, and responses to diverse environmental factors.

Triacylglycerols compositions, soluble and bound phenolics of red sorghums, and their radical scavenging and anti-inflammatory activities.

Six commercial red sorghum varieties (Tong Za 117, 141, 142 and 143, Chi Za 109 and 101) were investigated for their triacylglycerol (TAG) profiles, soluble and bound phenolics, and radical scavenging and anti-inflammatory activities. A total of 21 TAGs were identified in red sorghum oils for the first time. Total phenolic (TPC) and flavonoid contents (TFC) in the soluble or bound phenolic fractions differed among red sorghums. Significant correlation among TPC, TFC and DPPH radical scavenging activities was observed in both fractions. Except for caffeic acid, most of phenolic acids in red sorghums are in the bound form. Soluble 3-deoxyanthocyanidins contents (2.12-57.14 µg/g) were significantly higher than those of bound forms (0.01-0.18 µg/g) regardless of sorghum varieties and types of 3-deoxyanthocyanidins. Moreover, the stronger anti-inflammatory capacity of soluble phenolic fraction in Tong Za 117 correlated with its higher TPC, TFC and radical scavenging activity than those of its bound counterpart.