A comprehensive analysis of patients with cerebral arteriovenous malformation with headache: assessment of risk factors and treatment effectiveness.

BACKGROUND: Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. METHODS: This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). RESULTS: A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173-2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082-1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307-2.439, p < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.

Identification and Characterization of Colletotrichum Species Associated with Anthracnose Disease of Plum.

Plum (Prunus salicina Lindl.) is commercially cultivated worldwide for the high levels of nutrients in the fruit. In recent years, anthracnose has been severe in some plum planting areas in China, resulting in a large number of necrotic leaves, blight and pre-mature leaf fall. In this study, anthracnose samples of plum leaves were collected from Hezhou, Guilin and Lipu, Guangxi Province, and Meishan city, Abe Tibetan and Qiang autonomous prefecture of Sichuan Province. Characteristics of mycelia on PDA, morphology of appressoria and conidia, and analysis of sequences of several marker regions (internal transcribed spacer [ITS] region, glyceraldehyde-3-phosphate dehydrogenase [GAPDH], chitin synthase [CHS-1], histone H3 [HIS3], actin [ACT], ß-tubulin [TUB2], and the intergenic region between apn2 and MAT1-2-1 [ApMat]). The resulting 101 Colletotrichum isolates obtained were identified as eight species: C. fructicola (50.5%), C. siamense (24.8%), C. karsti (8.9%), C. plurivorum (7.9%), C. aeschynomenes (3.9%), C. gloeosporioides (2%), C. celtidis (1%) and C. phyllanthi (1%). Representatives of all eight Colletotrichum species were found to cause disease on wounded leaves of plum seedlings in pathogenicity assays. As far as we are aware, this is the first report of anthracnose of plum caused by C. celtidis and C. phyllanthi in China.

Epiphytic and endophytic bacteria on Camellia oleifera phyllosphere: exploring region and cultivar effect.

The epiphytic and endophytic bacteria play an important role in the healthy growth of plants. Both plant species and growth environmental influence the bacterial population diversity, yet it is inconclusive whether it is the former or the latter that has a greater impact. To explore the communities of the epiphytic and endophytic microbes in Camellia oleifera, this study assessed three representative C. oleifera cultivars from three areas in Hunan, China by Illumina high-throughput sequencing. The results showed that the diversity and species richness of endophytic microbial community in leaves were significantly higher than those of microbial community in the epiphytic. The diversity and species richness of epiphytic and endophytic microbes are complex when the same cultivar was grown in different areas. The C. oleifera cultivars grown in Youxian had the highest diversity of epiphytic microbial community, but the lowest abundance, while the cultivars grown in Changsha had the highest diversity and species richness of endophytic microbes in leaves. It was concluded that the dominant phylum mainly included Proteobacteria, Actinobacteriota and Firmicutes through the analysis of the epiphytic and endophytic microbial communities of C. oleifera. The species and relative abundances of epiphytic and endophytic microbial community were extremely different at the genus level. The analysis of NMDS map and PERMANOVA shows that the species richness and diversity of microbial communities in epiphytes are greatly influenced by region. However, the community structure of endophytic microorganisms in leaves is influenced by region and cultivated varieties, but the influence of cultivars is more significant. Molecular ecological network analysis showed that the symbiotic interaction of epiphytic microbial community was more complex.

First Report of Anthracnose Caused by Colletotrichum plurivorum on Passion fruit in Guangxi, China.

Passion fruit (Passiflora edulis Sims.) is popular for its rich taste and nutritional value. The planting area of passion fruit in Guangxi has reached 24,300 ha, with an annual output of 380,000 t (Qian 2023). In March 2023, leave spots on more than half of the plants (cv. Qinmi "NO.9"). Moreover, the incidence of disease on the leaves was approximately 20% in Shabu Town, Qinnan District, Qinzhou City, Guangxi, China (N20˚54'-22˚41', E107˚27'-109˚56'). Leaf diseases were orbicular or irregular in shape, white, whitish-grey, yellowish, or gray in color. When leaves were severely affected, larger blotches were formed with yellow halos. For pathogen isolation, three diseased leaf samples were collected from three gardens, respectively, and 5×5 mm tissues were cut from infected margins, surface-disinfected in 75% ethanol for 15 s, followed by 2% sodium hypochlorite for 1 min, rinsed three times with sterile water, and incubated on PDA at 25°C under 12/12 h light/darkness. After 5 days, ninety cultures were isolated, sixty isolates with similar morphology were retained, and three representative isolates BY-1, BY-2, and BY-4 were randomly selected for further study. On PDA, colonies of the three isolates displayed white or grayish-white. Conidia were single-celled, hyaline, and cylindrical, measuring 17.3±1.5 × 6.3±0.7 µm, 17.8±1.7 × 6.0±0.6 µm, and 16.3±1.4 × 6.4±0.6 µm (n=90) for BY-1, BY-2, and BY-4, respectively. Appressoria were single, brown or black, and irregular in shape, measuring 10.2±1.1×6.5±0.5 µm, 10.5±1.3×7.3±0.6, and 10.9±0.8×7.0±0.8 (n=90) for BY-1, BY-2, and BY-4, respectively. These morphological characteristics were similar to Colletotrichum spp. as previously described (Damm et al. 2019). The isolates were further identified by sequencing the internal transcribed spacer (ITS-ITS1/ITS4), glyceraldehyde-3-phosphate dehydrogenase (GAPDH-GDF/GDR), actin (ACT-512F/783R), partial sequences of the chitin synthase 1 (CHS-1-79F/354R), and beta-tubulin 2 (TUB2-T1/Bt2b) (Zhang et al. 2023). All sequences were deposited in GenBank (ITS: OR741759 to OR741761, GAPDH: OR767654 to OR767656, ACT: OR767657 to OR767659, CHS-1: OR767660 to OR767662, TUB2: OR767651 to OR767653). A phylogenetic tree was built with RAxML version 8.2.10 based on concatenated sequences of ITS-GAPDH-ACT-CHS-1-TUB2. The results revealed that the three isolates clustered with C. plurivorum. To confirm the pathogenicity of the three isolates, attached leaves of healthy 5-month-old passion fruit plants were injured in the middle region with sterile toothpicks and inoculated with 20 µL of spore suspension (106 conidia/mL), and the noninoculated control received 0.05% Tween-20 (6 leaves/plant, 3 plants/treatment). The inoculated plants were kept in a greenhouse at 25°C and covered with plastic bags to maintain high humidity. After 9 days, all inoculated leaves were symptomatic, whereas no symptoms were observed in the control. C. plurivorum was reisolated from infected leaves, confirming Koch's postulates. C. plurivorum has been reported to infect Abelmoschus esculentus (Batista et al. 2020) and Carya illinoinensis in China (Zhang et al. 2023). However, this is the first report of anthracnose caused by C. plurivorum on passion fruit in China. The results can provide a robust basis for scientific prevention and control of anthracnose.

Lesion-Filling Index from Quantitative DSA Correlates with Hemorrhage of Cerebral AVM.

BACKGROUND AND PURPOSE: Rupture is the most life-threatening manifestation of cerebral AVMs. This study aimed to explore the hemodynamic mechanism of AVM rupture. We introduced a new quantitative DSA parameter that can reflect the degree of intranidal blood stasis, called the lesion-filling index. MATERIALS AND METHODS: This study examined patients with AVMs who had undergone both DSA and MR imaging between 2013 and 2014. Clinical presentations, angioarchitecture, and hemodynamic parameters generated from quantitative DSA were analyzed using univariate and multivariable logistic regression. The lesion-filling index was defined as the arterial diagnostic window divided by the volume of the AVM. To assess the correlation between the lesion-filling index and rupture, we incorporated the lesion-filling index into 2 published prediction models widely recognized for predicting AVM rupture risk, R2eD and VALE. The DeLong test was used to examine whether the addition of the lesion-filling index improved predictive efficacy. RESULTS: A total of 180 patients with AVMs were included. The mean lesion-filling index values in the ruptured group were higher compared with the unruptured group (390.27 [SD, 919.81] versus 49.40 [SD, 98.25]), P < .001). A higher lesion-filling index was significantly correlated with AVM rupture in 3 different multivariable logistic models, adjusting for angioarchitecture factors (OR = 1.004, P = .02); hemodynamic factors (OR = 1.005, P = .009); and combined factors (OR = 1.004, P = .03). Both R2eD (area under the curve, 0.601 versus 0.624; P = .15) and VALE (area under the curve, 0.603 versus 0.706; P < .001) predictive models showed improved predictive performance after incorporating the lesion-filling index and conducting 10-fold cross-validation. CONCLUSIONS: The lesion-filling index showed a strong correlation with AVM rupture, suggesting that overperfusion is the hemodynamic mechanism leading to AVM rupture.

De-nitrosylation Coordinates Appressorium Function for Infection of the Rice Blast Fungus.

As a signaling molecule, nitric oxide (NO) regulates the development and stress response in different organisms. The major biological activity of NO is protein S-nitrosylation, whose function in fungi remains largely unclear. Here, it is found in the rice blast fungus Magnaporthe oryzae, de-nitrosylation process is essential for functional appressorium formation during infection. Nitrosative stress caused by excessive accumulation of NO is harmful for fungal infection. While the S-nitrosoglutathione reductase GSNOR-mediated de-nitrosylation removes excess NO toxicity during appressorium formation to promote infection. Through an indoTMT switch labeling proteomics technique, 741 S-nitrosylation sites in 483 proteins are identified. Key appressorial proteins, such as Mgb1, MagB, Sps1, Cdc42, and septins, are activated by GSNOR through de-nitrosylation. Removing S-nitrosylation sites of above proteins is essential for proper protein structure and appressorial function. Therefore, GSNOR-mediated de-nitrosylation is an essential regulator for appressorium formation. It is also shown that breaking NO homeostasis by NO donors, NO scavengers, as well as chemical inhibitor of GSNOR, shall be effective methods for fungal disease control.

Numerical simulation of ultrawideband supercontinuum generation covering a 2-20 µm waveband in cascaded all-soft-glass fiber.

We designed a cascaded all-soft-glass fiber structure and simulate midinfrared 2-20 µm ultrawideband supercontinuum (SC) generation numerically. The cascaded fiber structure consists of a 1.5 m I n F 3 fiber, a 0.2 m chalcogenide photonic crystal fiber, and a 0.2 m tellurium-based chalcogenide photonic crystal fiber. Using a 2 µm pulse pumping this cascaded structure, the generated SC covering the wavelengths longer than 20 µm has been demonstrated theoretically. The 30 dB bandwidth reaches 20.87 µm from 1.44 to 22.31 µm. The effect of different pulse widths on SC generation is considered. With the increase of peak power and the decrease of pulse width, the energy of SC in the 15-20 µm waveband increases gradually. The mechanism of SC broadening process has also been analyzed. The SC generation of more than 20 µm in this cascade structure is caused by the self-phase modulation, soliton effects, four-wave mixing, and redshifted dispersive wave. This method demonstrates the possibility of generating ultrawide bandwidth SCs up to a 20 µm waveband by a commercial 2 µm pump source and all-fiber structure.

Perineural invasion in cervical cancer: A multicenter retrospective study.

OBJECTIVE: The study aimed to evaluate the accuracy of perineural invasion (PNI) diagnosis in cervical cancer, and to analyze the impact of PNI on the prognosis and postoperative adjuvant treatment decisions for cervical cancer. METHODS: A retrospective pathological review of PNI in cervical cancer was conducted from 2004 to 2016 in 15 hospitals. RESULTS: This study included a total of 1208 cases, comprising 273 cases with PNI and 935 cases without. The false positive rate and false negative rate of PNI diagnosis were 5.35% (50/935) and 33.33% (91/273), respectively. Adenocarcinoma, deep stromal invasion, lymphovascular space invasion (LVSI) (+), and margin involvement were independent risk factors for PNI. Both 5-year overall survival rate (OS) and 5-year disease-free survival rate (DFS) of PNI group were worse than non-PNI group. PNI was an independent risk factor for 5-year OS and 5-year DFS. In cases receiving standard postoperative adjuvant treatment, among those with two intermediate-risk factors, both 5-year OS and DFS were worse in the PNI group. Among cases with three intermediate-risk factors or at least one high-risk factor, there was no difference in 5-year OS between the two groups, but 5-year DFS was worse in the PNI group. CONCLUSION: The diagnosis of PNI in cervical cancer was not accurate. Adenocarcinoma, deep stromal invasion, LVSI, and margin involvement were independent risk factors for PNI. PNI was an independent risk factor for 5-year OS and DFS. PNI has the potential to serve as a new high-risk factor, thus providing guidance for postoperative adjuvant therapy.

The impact of non-stereotypical gender role endorsement in live broadcasting on consumers' purchase intention.

Introduction: Non-stereotypical gender role endorsement is becoming more common in e-commerce live broadcasting. However, there is relatively little research on this topic, and the mechanism of its impact on purchase intention is not yet clear. Based on schema theory and experimental methods, this study explores the impact of non-stereotypical gender role endorsement (compared to stereotypical gender role endorsement) on purchase intention in e-commerce live broadcasting. Besides, we take traditional gender ideology as the moderating variable. Methods: We first selected experimental materials available for formal experiments through two pre-experiments. Secondly, this study conducted experiments on male/female product groups, respectively. Participants were recruited through the Credamo platform for both experiments. Results: Experiment 1 indicates that for female product, stereotypical gender role endorsement triggers higher consumer purchase intention compared to non-stereotypical gender role endorsement. The subsequent moderating effect test results manifest that traditional gender ideology plays a moderating role in this effect. Experiment 2 shows that for male product, there is no significant difference in the impact of the two types of endorsement on consumers' purchase intention. In other words, non-stereotypical gender role endorsement does affect consumers' purchase intention, but this effect exists only in female product, and is more significant for consumers with a high level of traditional gender ideology. Discussion: This study not only has certain theoretical significance for expanding the application boundaries of schema theory and congruence between celebrities and products endorsed, but also has practical significance for brand owners and streamers to effectively adopt non-stereotypical gender role endorsement to enhance purchase intention.

Integrated analysis of single-cell and bulk RNA sequencing data reveals prognostic characteristics of lysosome-dependent cell death-related genes in osteosarcoma.

BACKGROUND: Tumor cells exhibit a heightened susceptibility to lysosomal-dependent cell death (LCD) compared to normal cells. However, the role of LCD-related genes (LCD-RGs) in Osteosarcoma (OS) remains unelucidated. This study aimed to elucidate the role of LCD-RGs and their mechanisms in OS using several existing OS related datasets, including TCGA-OS, GSE16088, GSE14359, GSE21257 and GSE162454. RESULTS: Analysis identified a total of 8,629 DEGs1, 2,777 DEGs2 and 21 intersection genes. Importantly, two biomarkers (ATP6V0D1 and HDAC6) linked to OS prognosis were identified to establish the prognostic model. Significant differences in risk scores for OS survival were observed between high and low-risk cohorts. Additionally, scores of dendritic cells (DC), immature DCs and γδT cells differed significantly between the two risk cohorts. Cell annotations from GSE162454 encompassed eight types (myeloid cells, osteoblastic OS cells and plasma cells). ATP6V0D1 was found to be significantly over-expressed in myeloid cells and osteoclasts, while HDAC6 was under-expressed across all cell types. Moreover, single-cell trajectory mapping revealed that myeloid cells and osteoclasts differentiated first, underscoring their pivotal role in patients with OS. Furthermore, ATP6V0D1 expression progressively decreased with time. CONCLUSIONS: A new prognostic model for OS, associated with LCD-RGs, was developed and validated, offering a fresh perspective for exploring the association between LCD and OS.

High-throughput visualization mutation screening technology to enhance the specificity of CadR based whole-cell cadmium biosensor.

As a heavy metal pollutant, Cd2+ often enters the human body through the food chain causing great harm to human health. Whole-cell biosensor is an emerging technology for rapid on-site detection of heavy metals with the advantages of inexpensive, fast to mass-produce, and strong in anti-interference resistance, but suffering from insatisfactory specificity. In this study, a strategy of Adjacent Site Saturation Mutation (ASSM) was designed to improve the specificity of transcription factor CadR, which acted as the recognition element and determined the specificity of whole cell Cd2+ biosensors. A specific saturated library was constructed using the strategy of adjacent mutation. After two rounds of high-throughput visual screening, a whole-cell biosensor with good response to Cd2+, and with significant weakened Hg2+ interference was obtained. The optimized whole-cell biosensor showed a linear dynamic concentration range from 500 nM to 100 µM, a detection limit of 0.079 µM, and has satisfactory specificity and anti-interference. The ASSM strategy proposed in this study can provide a new method for the application of synthetic biology in food safety detection, indicating the importance of whole-cell biosensors for the detection of heavy metals.

Nonlinear Static Bending and Forced Vibrations of Single-Layer MoS2 with Thermal Stress.

Single-layer molybdenum disulfide (MoS2) has been a research focus in recent years owing to its extensive potential applications. However, how to model the mechanical properties of MoS2 is an open question. In this study, we investigate the nonlinear static bending and forced vibrations of MoS2, subjected to boundary axial and thermal stresses using modified plate theory with independent in-plane and out-of-plane stiffnesses. First, two nonlinear ordinary differential equations are obtained using the Galerkin method to represent the nonlinear vibrations of the first two symmetrical modes. Second, we analyze nonlinear static bending by neglecting the inertial and damping terms of the two equations. Finally, we explore nonlinear forced vibrations using the method of multiple scales for the first- and third-order modes, and their 1:3 internal resonance. The main results are as follows: (1) The thermal stress and the axial compressive stress reduce the MoS2 stiffness significantly. (2) The bifurcation points of the load at the low-frequency primary resonance are much smaller than those at high frequency under single-mode vibrations. (3) Temperature has a more remarkable influence on the higher-order mode than the lower-order mode under the 1:3 internal resonance.

First Report of Leaf Rot Caused by Apiospora paraphaeosperma on Lily in Wuhan, China.

Lily (Lilium spp.) is a valuable ornamental bulb flower plant in Liliaceae, and its bulbs have high edible and medicinal value. Compared with bulb propagation of other lilies, seed propagation and short growth period are the most significant characteristics of Lilium×formolongi. In 2023, leaf rot disease (LRD) was observed on approximately 70% of the Lilium×formolongi seedlings sown in an experimental greenhouse in Wuhan, Hubei province, China. Irregular brown water-soaked spots were discovered in the early stages of infected seedlings. Then, spots spread throughout the leaves and caused the leaves to brown, soften, and wilted. A pathogen associated with symptoms was isolated by incubating sterilized leaves on potato dextrose agar plates at 25 ℃ for 2-3 days. Then, a pure single colony was isolated through a single hyphal tip isolation method. The fungal colony was white with abundant aerial mycelium and produced a yellow pigment diffusible into the agar. Microscopically, isolated mycelia were reticulate and pale yellow, while conidia were dark brown, smooth, and spherical, 7.31 to 6.98 × 4.03 to 3.87µm (average 5.44×5.41µm; n=30); oval in lateral view, and had a light stripe in the middle. To identify the species of the fungus at the molecular level, ITS and EF-1α genes were amplified and sequenced using primers ITS1/ITS4 (M Gardes et al. 1993) and 758F/986R (Carbone and Kohn 1999). The BLAST results in GenBank showed that the ITS(OR523578) and EF-1α(PP066842) sequences of LRD shared 99.82% and 99.24% identity with the distinct Apiospora paraphaeosperma strains (GenBank accession MT040110, ON806628.1, respectively). Combined with the morphology of the colony and conidium, the fungus was identified as Ap. paraphaeosperma. In the pathogenicity test, six healthy leaves were inoculated with mycelium disc and then kept in an incubator (22 ℃, 90% humidity, 16h light /8h darkness). The inoculated leaves showed necrosis and wilt symptoms similar to those observed in the greenhouse, while the control leaves were asymptomatic. A re-isolation, morphology identification and DNA sequencing of the fungus confirmed its infection with Ap. paraphaeosperma in Lilium spp. At present, rot caused by Ap. paraphaeosperma has only been reported in Thailand and South Korea, both of which are found on bamboo stems (Hyde et al. 2016; Sun Lul Kwon et al. 2022). As far as we know, this is the first report of leaf rot of lily caused by Ap. paraphaeosperma in China. This report can help identify this disease and further develop effective control measures.

Elevated cortical blood flow insufficiency volume as a predictor of adverse outcomes in aneurysmal subarachnoid hemorrhage: a large prospective quantitative computed tomography perfusion study.

PURPOSE: Early hypoperfusion changes exist in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate a readily obtainable quantitative computed tomography perfusion (CTP) parameter that could assist in quickly identifying patients at risk of delayed cerebral ischemia (DCI) and poor 90-day functional outcomes on admission. METHODS: We prospectively collected data between 2021.04 and 2022.12. Preoperative CTP data were post-processed using RAPID software. The cortical blood flow insufficiency (CBFI) was defined as Time-to-maximum > 4.0 s. Patients were categorized into four groups according to CBFI volume distribution. To minimize differences among the groups, we employed stabilized inverse probability of treatment weighting (sIPTW). The primary outcome was DCI and poor 90-day functional outcomes (modified Rankin Scale, 3-6) was the secondary outcome. Multivariable Cox or Logistic analysis were performed to estimate the association between CBFI volume and the study outcomes, both before and after sIPTW. RESULTS: At baseline, the mean (SD) age of the 493 participants was 55.0 (11.8) years, and 299 (60.6%) were female. One hundred and seven participants with DCI and eighty-six participants with poor 90-day functional outcomes were identified. After sIPTW, CBFI volume demonstrated a significant association with DCI (Cox regression: Group 4 versus Group 1, HR 3.69, 95% CI 1.84-7.01) and poor 90-day functional outcomes (Logistic regression: Group 4 versus Group 1, OR 4.61, 95% CI 2.01-12.50). CONCLUSION: In this study, an elevated preoperative CBFI volume was associated with adverse outcomes in aSAH patients. More well-designed studies are needed to confirm this association.

Comparison of 68Ga-FAPI-04 PET/CT with 18F-FDG PET/CT for diagnosis and staging of gastric and colorectal cancer.

OBJECTIVE: The objective of this study is to evaluate the effectiveness of 68Ga-FAPI-04 PET/computed tomography (CT) for the diagnosis of primary and metastatic gastric cancer and colorectal cancer lesions as compared with 18F-FDG PET/CT. MATERIALS AND METHODS: Fifty-nine patients who underwent both 18F-FDG and 68Ga-FAPI-04 for initial staging or restaging were enrolled. Histopathological findings and clinical imaging follow-up were used as the reference standard. The diagnostic performance and TNM staging of the two tracers were calculated and compared. The maximum standardized uptake value (SUVmax), tumour-to-mediastinal blood pool ratio (TBR) (lesions SUVmax/ascending aorta SUVmean), and tumour-to-normal liver parenchyma ratio (TLR) (lesions SUVmax/liver SUVmean) of primary and metastatic lesions between two imaging modalities were measured and compared using the Wilcoxon signed-rank test and paired t-test. RESULTS: The two imaging agents are comparable for the detection of primary tumors. The sensitivity of 68Ga-FAPI-04 PET/CT was higher than that of 18F-FDG PET/CT for detecting lymph node metastases, peritoneal metastases, liver metastases, and bone metastases. In the patient-based analysis, the TLR for all lesions was significantly higher with 68Ga-FAPI-04 PET/CT than with 18F-FDG PET/CT (all P < 0.05). The accuracy (92.2 vs. 70.3%, P = 0.002) and sensitivity of 68Ga-FAPI-04 were significantly higher than that of 18F-FDG (78.6 vs. 71.4%, P = 0.011) in determining the lymph node status. 68Ga-FAPI-04 has a higher accuracy in staging (P = 0.041), which is mainly due to the ability of distant metastases detection. CONCLUSION: 68Ga-FAPI-04 PET/CT may be superior in evaluating the diagnostic efficiency and staging accuracy of gastric and colorectal cancer.

Sirt5-mediated lysine desuccinylation regulates oxidative stress adaptation in Magnaporthe oryzae during host intracellular infection.

Plant pathogenic fungi elaborate numerous detoxification strategies to suppress host reactive oxygen species (ROS), but their coordination is not well-understood. Here, we show that Sirt5-mediated protein desuccinylation in Magnaporthe oryzae is central to host ROS detoxification. SIRT5 encodes a desuccinylase important for virulence via adaptation to host oxidative stress. Quantitative proteomics analysis identified a large number of succinylated proteins targeted by Sirt5, most of which were mitochondrial proteins involved in oxidative phosphorylation, TCA cycle, and fatty acid oxidation. Deletion of SIRT5 resulted in hypersuccinylation of detoxification-related enzymes, and significant reduction in NADPH : NADP+ and GSH : GSSG ratios, disrupting redox balance and impeding invasive growth. Sirt5 desuccinylated thioredoxin Trx2 and glutathione peroxidase Hyr1 to activate their enzyme activity, likely by affecting proper folding. Altogether, this work demonstrates the importance of Sirt5-mediated desuccinylation in controlling fungal process required for detoxifying host ROS during M. oryzae infection.

circNOX4 activates an inflammatory fibroblast niche to promote tumor growth and metastasis in NSCLC via FAP/IL-6 axis.

BACKGROUND: Cancer-associated fibroblasts (CAFs) orchestrate a supportive niche that fuels cancer metastatic development in non-small cell lung cancer (NSCLC). Due to the heterogeneity and plasticity of CAFs, manipulating the activated phenotype of fibroblasts is a promising strategy for cancer therapy. However, the underlying mechanisms of fibroblast activation and phenotype switching that drive metastasis remain elusive. METHODS: The clinical implications of fibroblast activation protein (FAP)-positive CAFs (FAP+CAFs) were evaluated based on tumor specimens from NSCLC patients and bioinformatic analysis of online databases. CAF-specific circular RNAs (circRNAs) were screened by circRNA microarrays of primary human CAFs and matched normal fibroblasts (NFs). Survival analyses were performed to assess the prognostic value of circNOX4 in NSCLC clinical samples. The biological effects of circNOX4 were investigated by gain- and loss-of-function experiments in vitro and in vivo. Fluorescence in situ hybridization, luciferase reporter assays, RNA immunoprecipitation, and miRNA rescue experiments were conducted to elucidate the underlying mechanisms of fibroblast activation. Cytokine antibody array, transwell coculture system, and enzyme-linked immunosorbent assay (ELISA) were performed to investigate the downstream effectors that promote cancer metastasis. RESULTS: FAP+CAFs were significantly enriched in metastatic cancer samples, and their higher abundance was correlated with the worse overall survival in NSCLC patients. A novel CAF-specific circRNA, circNOX4 (hsa_circ_0023988), evoked the phenotypic transition from NFs into CAFs and promoted the migration and invasion of NSCLC in vitro and in vivo. Clinically, circNOX4 correlated with the poor prognosis of advanced NSCLC patients. Mechanistically, circNOX4 upregulated FAP by sponging miR-329-5p, which led to fibroblast activation. Furthermore, the circNOX4/miR-329-5p/FAP axis activated an inflammatory fibroblast niche by preferentially inducing interleukin-6 (IL-6) and eventually promoting NSCLC progression. Disruption of the intercellular circNOX4/IL-6 axis significantly suppressed tumor growth and metastatic colonization in vivo. CONCLUSIONS: Our study reveals a role of the circRNA-induced fibroblast niche in tumor metastasis and highlights that targeting the circNOX4/FAP/IL-6 axis is a promising strategy for the intervention of NSCLC metastasis.

A novel approach has been developed to produce pure plant-based gel soy yogurt by combining soy proteins (7S/11S), high pressure homogenization, and glycation reaction.

This research sought to examine how the physicochemical characteristics of soy globulins and different processing techniques influence the gel properties of soy yogurt. The goal was to improve these gel properties and rectify any texture issues in soy yogurt, ultimately aiming to produce premium-quality plant-based soy yogurt. In this research study, the investigation focused on examining the impact of 7S/11S, homogenization pressure, and glycation modified with glucose on the gel properties of soy yogurt. A plant-based soy yogurt with superior gel and texture properties was successfully developed using a 7S/11S globulin-glucose conjugate at a 1:3 ratio and a homogenization pressure of 110 MPa. Compared to soy yogurt supplemented with pectin or gelatin, this yogurt demonstrated enhanced characteristics. These findings provide valuable insights into advancing plant protein gels and serve as a reference for cultivating new soybean varieties by soybean breeding experts.

The TGF-ß/MMP9/RAGE axis induces sRAGE secretion by neutrophils and promotes oral carcinogenesis.

In the tumor microenvironment, transforming growth factor ß (TGF-ß) contributes to neutrophil development toward a pro-tumor phenotype; however, the molecular mechanism by which this occurs remains unclear. Therefore, we explored the role of TGF-ß in N2 neutrophil polarization and the subsequent effect on oral leukoplakia/oral squamous cell carcinoma (OL/OSCC) cells. The TGF-ß-stimulated N2 culture supernatant promoted the proliferation of OL/OSCC cells. Analysis of the N2 supernatant using a cytokine array revealed significantly upregulated expression of soluble forms of receptor for advanced glycation end products (RAGE). TGF-ß was found to induce the expression of RAGE and matrix metalloproteinase 9 (MMP9) in neutrophils. Additionally, MMP9 treatment could cleave RAGE and promote its secretion by neutrophils, thereby promoting cancer cell proliferation. In an established mouse model of oral cancer using 4NQO, RAGE were found to be highly expressed. Importantly, neutralizing antibodies against RAGE significantly inhibited oral cancer progression in mice. Analysis of clinical data from the TCGA database revealed that RAGE and MMP9 are highly expressed in head and neck squamous cell carcinoma (HNSCC) and that RAGE expression is significantly positively correlated with neutrophil infiltration. In conclusion, our results indicate that TGF-ß promotes N2 neutrophil polarization through upregulation of soluble RAGE (sRAGE) secretion, leading to OSCC cell proliferation. Our findings also suggest that the sRAGE formed during N2 polarization may be a potential therapeutic target in OL/OSCC.

Fruit Anthracnose on Cavendish bananas Caused by Colletotrichum fructicola in Guangxi, China.

Cavendish banana (Musa spp. AAA group) is one of the main fruit crops worldwide. It is widely planted in Guangdong, Hainan, Guangxi, Fujian and Yunnan provinces in southern China. In November 2020, banana fruits with anthracnose symptoms were collected from Dayu Town (N 23.17°, E 109.80°), Guigang City, and Chengjun Town (N 22.60°, E 110.00°), Yulin City, Guangxi Province, China, where the disease was found on about 70% of the banana plants, and on individual fruit, up to 10% of the surface was covered with symptoms. The symptoms initially began with rust-colored spots on the surface of the immature fruit, which gradually became sunken and cracked as the disease progressed. Small tissues (5×5 mm) from the pericarp at the junction of disease and health were surface-disinfected in 75% ethanol for 10 s, 2% sodium hypochlorite (NaClO) for 1 min, and washed three times in sterile water. Tissue pieces were placed on potato dextrose ager (PDA) and incubated at 25°C. Fifty-nine morphologically similar colonies were obtained after 5 days of incubation, with 100% isolation frequency. Of 59 isolates, GG1-3 isolated from Guigang City and YL4-2 isolated from Yulin City were selected as representative strains for intensive study. Mycelia were off-white for both isolates and conidia obtained from PDA were cylindrical, unicellular, hyaline and obtuse ends, with sizes of 11.5 ± 1.8×3.9 ± 0.8 µm (n=60) and 11.5 ± 1.6×4.1 ± 0.6 µm (n=60) for GG1-3 and YL4-2, respectively (Prihastuti et al. 2009). Genomic DNA was extracted from 7-day-old aerial mycelia using a DNAsecure Plant Kit (Tiangen Biotech, China). The internal transcribed spacer (ITS), the intergenic region of apn2 and MAT1-2-1 (ApMAT) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were amplified and sequenced (White et al. 1990; Silva et al.2012; Templeton et al. 1992). Sequences were deposited in GenBank (ITS, OR596961 to OR596962; GAPDH, OR661771 to OR661772; APMAT, OR661773 to OR661774) and showed 100% identities with the corresponding type strains sequences of C. fructicola. Phylogenetic tree was constructed with software raxmlGUI v.2.0.0 based on sequences of multiple loci (ITS, GAPDH and ApMAT) and Maximum Likelihood method. Phylogenetic analysis revealed that the two isolates and C. fructicola were clustered in the same clade, with 94% bootstrap support. According to morphology and phylogenetic analysis, the two isolates GG1-3 and YL4-2 were identified as C. fructicola. For pathogenicity tests, healthy fruits were surface sterilized with 75% ethanol followed by a wash with sterilized water. Five adjacent needle punctures in a 5-mm-diameter circle were made with a sterilized needle on healthy fruits, followed by inoculation with 20 µL of conidial suspension (106 spores/ml), and sterilized water was used as controls. All banana fruit were incubated in a humid chamber at 28°C. After 4 days, all inoculated fruits showed visible symptoms and had rust-colored spots on the margins, while control banana fruits remained symptomless. The fungus was isolated from the inoculated fruit and the isolates were found to match the morphological and molecular characteristics of the original isolates, confirming Koch's hypothesis. To our knowledge, this is the first report of fruit anthracnose on Cavendish bananas caused by C. fructicola in China. This study will provide valuable information for prevention and management of anthracnose on banana fruit.