The Arabidopsis E3 ubiquitin ligase PUB4 regulates BIK1 and is targeted by a bacterial type-III effector.

Plant immunity is tightly controlled by a complex and dynamic regulatory network, which ensures optimal activation upon detection of potential pathogens. Accordingly, each component of this network is a potential target for manipulation by pathogens. Here, we report that RipAC, a type III-secreted effector from the bacterial pathogen Ralstonia solanacearum, targets the plant E3 ubiquitin ligase PUB4 to inhibit pattern-triggered immunity (PTI). PUB4 plays a positive role in PTI by regulating the homeostasis of the central immune kinase BIK1. Before PAMP perception, PUB4 promotes the degradation of non-activated BIK1, while after PAMP perception, PUB4 contributes to the accumulation of activated BIK1. RipAC leads to BIK1 degradation, which correlates with its PTI-inhibitory activity. RipAC causes a reduction in pathogen-associated molecular pattern (PAMP)-induced PUB4 accumulation and phosphorylation. Our results shed light on the role played by PUB4 in immune regulation, and illustrate an indirect targeting of the immune signalling hub BIK1 by a bacterial effector.

A Regulatory Module Controlling Homeostasis of a Plant Immune Kinase.

Plant pattern recognition receptors (PRRs) perceive microbial and endogenous molecular patterns to activate immune signaling. The cytoplasmic kinase BIK1 acts downstream of multiple PRRs as a rate-limiting component, whose phosphorylation and accumulation are central to immune signal propagation. Previous work identified the calcium-dependent protein kinase CPK28 and heterotrimeric G proteins as negative and positive regulators of BIK1 accumulation, respectively. However, mechanisms underlying this regulation remain unknown. Here we show that the plant U-box proteins PUB25 and PUB26 are homologous E3 ligases that mark BIK1 for degradation to negatively regulate immunity. We demonstrate that the heterotrimeric G proteins inhibit PUB25/26 activity to stabilize BIK1, whereas CPK28 specifically phosphorylates conserved residues in PUB25/26 to enhance their activity and promote BIK1 degradation. Interestingly, PUB25/26 specifically target non-activated BIK1, suggesting that activated BIK1 is maintained for immune signaling. Our findings reveal a multi-protein regulatory module that enables robust yet tightly regulated immune responses.

Microbiota and metabolite alterations in pancreatic head and body/tail cancer patients.

Pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) have distinct clinical and biological behaviors. The microbial and metabolic differences in PHC and PBTC have not been studied. The pancreatic microbiota and metabolome of 15 PHC and 8 PBTC tissues and their matched nontumor tissues were characterized using 16S rRNA amplicon sequencing and untargeted metabolomics. At the genus level, Bradyrhizobium was increased while Corynebacterium and Ruminococcus were decreased in the PHC tissues (Head T) compared with the matched nontumor tissues (Head N) significantly. Shuttleworthia, Bacillus, and Bifidobacterium were significantly decreased in the PBTC tissues (Body/Tail T) compared with the matched nontumor tissues (Body/Tail N). Significantly, Ileibacterium was increased whereas Pseudoxanthomonas was decreased in Head T and Body/Tail T, and Lactobacillus was increased in Head T but decreased in Body/Tail T. A total of 102 discriminative metabolites were identified between Head T and Head N, which were scattered through linoleic acid metabolism and purine metabolism pathways. However, there were only four discriminative metabolites between Body/Tail T and Body/Tail N, which were related to glycerophospholipid metabolism and autophagy pathways. The differential metabolites in PHC and PBTC were commonly enriched in alpha-linolenic acid metabolism and choline metabolism in cancer pathways. Eubacterium decreased in Head T was positively correlated with decreased linoleic acid while negatively correlated with increased arachidyl carnitine and stearoylcarnitine. Bacillus decreased in Body/Tail T was negatively correlated with increased L-carnitine. These microbiota and metabolites deserve further investigations to reveal their roles in the pathogenesis of PHC and PBTC, providing clues for future treatments.

An Integrated Multi-Omics Analysis Identifying Immune Subtypes of Pancreatic Cancer.

Limited studies have explored novel pancreatic cancer (PC) subtypes or prognostic biomarkers based on the altered activity of relevant signaling pathway gene sets. Here, we employed non-negative matrix factorization (NMF) to identify three immune subtypes of PC based on C7 immunologic signature gene set activity in PC and normal samples. Cluster 1, the immune-inflamed subtype, showed a higher response rate to immune checkpoint blockade (ICB) and had the lowest tumor immune dysfunction and exclusion (TIDE) scores. Cluster 2, the immune-excluded subtype, exhibited strong associations with stromal activation, characterized by elevated expression levels of transforming growth factor (TGF)-ß, cell adhesion, extracellular matrix remodeling, and epithelial-to-mesenchymal transition (EMT) related genes. Cluster 3, the immune-desert subtype, displayed limited immune activity. For prognostic prediction, we developed an immune-related prognostic risk model (IRPM) based on four immune-related prognostic genes in pancreatic cancer, RHOF, CEP250, TSC1, and KIF20B. The IRPM demonstrated excellent prognostic efficacy and successful validation in an external cohort. Notably, the key gene in the prognostic model, RHOF, exerted significant influence on the proliferation, migration, and invasion of pancreatic cancer cells through in vitro experiments. Furthermore, we conducted a comprehensive analysis of somatic mutational landscapes and immune landscapes in PC patients with different IRPM risk scores. Our findings accurately stratified patients based on their immune microenvironment and predicted immunotherapy responses, offering valuable insights for clinicians in developing more targeted clinical strategies.

PuHox52 promotes coordinated uptake of nitrate, phosphate, and iron under nitrogen deficiency in Populus ussuriensis.

It is of great importance to better understand how trees regulate nitrogen (N) uptake under N deficiency conditions which severely challenge afforestation practices, yet the underlying molecular mechanisms have not been well elucidated. Here, we functionally characterized PuHox52, a Populus ussuriensis HD-ZIP transcription factor, whose overexpression greatly enhanced nutrient uptake and plant growth under N deficiency. We first conducted an RNA sequencing experiment to obtain root transcriptome using PuHox52-overexpression lines of P. ussuriensis under low N treatment. We then performed multiple genetic and phenotypic analyses to identify key target genes of PuHox52 and validated how they acted against N deficiency under PuHox52 regulation. PuHox52 was specifically induced in roots by N deficiency, and overexpression of PuHox52 promoted N uptake, plant growth, and root development. We demonstrated that several nitrate-responsive genes (PuNRT1.1, PuNRT2.4, PuCLC-b, PuNIA2, PuNIR1, and PuNLP1), phosphate-responsive genes (PuPHL1A and PuPHL1B), and an iron transporter gene (PuIRT1) were substantiated to be direct targets of PuHox52. Among them, PuNRT1.1, PuPHL1A/B, and PuIRT1 were upregulated to relatively higher levels during PuHox52-mediated responses against N deficiency in PuHox52-overexpression lines compared to WT. Our study revealed a novel regulatory mechanism underlying root adaption to N deficiency where PuHox52 modulated a coordinated uptake of nitrate, phosphate, and iron through 'PuHox52-PuNRT1.1', 'PuHox52-PuPHL1A/PuPHL1B', and 'PuHox52-PuIRT1' regulatory relationships in poplar roots.

CPR5 positively regulates pattern-triggered immunity via a mediator protein.

Plant cells possess a two-layered immune system consisting of pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), mediated by cell surface pattern-recognition receptors and intracellular nucleotide-binding leucine-rich repeat receptors (NLRs), respectively. The CONSTITUTIVE EXPRESSION OF PR GENES 5 (CPR5) nuclear pore complex protein negatively regulates ETI, including ETI-associated hypersensitive response. Here, we show that CPR5 is essential for the activation of various PTI responses in Arabidopsis, such as resistance to the non-adapted bacterium Pseudomonas syringae pv. tomato DC3000 hrcC- . In a forward-genetic screen for suppressors of cpr5, we identified the mediator protein MED4. Mutation of MED4 in cpr5 greatly restored the defective PTI of cpr5. Our findings reveal that CPR5 plays opposite roles in regulating PTI and ETI, and genetically regulates PTI via MED4.

Rice extra-large G proteins play pivotal roles in controlling disease resistance and yield-related traits.

To better explore the potential of rice extra-large G (XLG) proteins in future breeding, we characterised the function of OsXLG1, OsXLG2 and OsXLG3 in disease resistance. Loss-of-function Osxlg2 and Osxlg3 mutants showed reduced resistance to the fungal pathogen Magnaporthe oryzae, whereas Osxlg1 mutants were specifically compromised in resistance to the bacterial pathogen Xanthomonas oryzae pv oryzae. Consistent with their effects on rice blast resistance, mutations in OsXLG2 and OsXLG3 caused greater defects than did mutations in OsXLG1 for chitin-induced defence responses. All three OsXLGs interacted with components of a surface immune receptor complex composed of OsCERK1, OsRLCK176 and OsRLCK185. Further characterisation of yield-related traits showed that the Osxlg3 mutants displayed reduced plant height, panicle length and 1000grain weight, whereas Osxlg1 mutants exhibited increased plant height, panicle length and 1000-grain weight. Together the study shows the differential contributions of the three OsXLG proteins to disease resistance to fungal and bacterial pathogens, their yield-related traits and provides insights for future improvement of rice production.

Anti-Psoriatic Effects of Middle Fragment of Chlamydial Plasmid-Encoded Protein pGP3 in an Imiquimod-Induced Psoriasis Mouse Model.

BACKGROUND Previously, we demonstrated that the chlamydial protein pGP3 forms a stable complex with LL-37 to neutralize its proinflammatory activity during the pathogenesis of psoriasis. The middle domain of pGP3 (pGP3M) is critical for the binding and neutralization of LL-37. Here, we further examined the mechanism underlying pGP3-mediated inhibition of psoriasis progression and evaluated the inhibitory effect of pGP3M on the development of psoriasis-like skin lesions in mice. MATERIAL AND METHODS Stock solutions of pGP3M and pGP3 (100 µg/mL) were prepared using sterile ultrapure water and intramuscularly injected into the left leg of the imiquimod (IMQ)-induced psoriasis mouse model. The severity of skin lesions was evaluated based on the psoriasis area and severity index score and ear skin thickness. The skin biopsy and blood samples were collected on the 8th day for histological analysis and inflammatory cytokines detection. RESULTS Erythema, scaling, and thickening were observed on the dorsal skin and the right ear skin of IMQ-treated mice. Treatment with pGP3 and pGP3M alleviated the IMQ-induced erythema, inflammatory cell infiltration, and scaly plaques. Compared with IMQ-treated and PBS-treated mice, pGP3- and PGP3M-treated mice had less inflammatory cell infiltration in skin tissues and had significantly reduced IL-17A, IFN-γ, and IL-22 levels in serum. CONCLUSIONS The anti-psoriatic efficacy of exogenous pGP3M was similar to that of pGP3. This indicated that pGP3M attenuated the IMQ-induced inflammatory and psoriatic symptoms in mice by binding and inhibiting LL-37. Further research is needed to examine the toxicity of pGP3 and pGP3M before clinical trial evaluation.

Chlamydial-Secreted Protease Chlamydia High Temperature Requirement Protein A (cHtrA) Degrades Human Cathelicidin LL-37 and Suppresses Its Anti-Chlamydial Activity.

BACKGROUND Chlamydia trachomatis is an obligate intracellular pathogen that can cause severe reproductive tract complications while ascending infection occurs. When spreading from cell to cell in a host, C. trachomatis utilizes various survival strategies to offset host defense mechanisms. One such strategy is to degrade host antimicrobial defense proteins before they can attack the invading C. trachomatis cells. MATERIAL AND METHODS We expressed and purified recombinant chlamydia high temperature requirement protein A (cHtrA) including 2 cHtrA mutants (MT-H143A and MT-S247A), and also extracted endogenous cHtrA. Proteins were identified and their purity evaluated by SDS-PAGE and Western blot. The anti-chlamydial activity and degradation of 5 antimicrobial peptides (cathelicidin LL-37, alpha-defensin-1 and -3, and ß-defensin-2 and -4) by cHtrA and 2 cHtrA mutants (MT-H143A and MT-S247A) were tested by immunoassay and Western blot. RESULTS Of the 5 antimicrobial peptides (cathelicidin LL-37, alpha-defensin-1 and -3, and ß-defensin-2 and -4) tested, cathelicidin LL-37 showed the strongest anti-chlamydial activity. Interestingly, cHtrA effectively and specifically degraded LL-37, suppressing its anti-chlamydial activity. The 2 cHtrA mutants (MT-H143A and MT-S247A) were unable to degrade LL-37. Comparison of cHtrA activity from C. trachomatis D, L2, and MoPn strains on LL-37 showed similar responses. CONCLUSIONS cHtrA may contribute to C. trachomatis pathogenicity by clearing the passage of invasion by specific LL-37 degradation.

[Effects of norepinephrine on proliferation and apoptosis of neonatal cardiac fibroblasts in rats].

OBJECTIVE: To investigate the effects of different concentrations of norepinephrine (NE) on proliferation and apoptosis of cultured cardiac fibroblasts (CFBs) from neonatal mice and to elucidate related mechanisms. METHODS: CFBs of Sprague-Dawley (SD) rats were isolated and cultured and divided into normal control group and different concentration of NE intervention groups (0.1, 1, 10, 50, and 100 µmol/L). Water soluble tetrazolium-1 (WST-1) assay was carried out to detect the viability of CFBs. Morphology of apoptosis cells was evaluated by fluorescence microscope with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expressions of collagen I, collagen III, pro-oncogene c-myc in CFBs were detected by reverse transcription-polymerase chain reaction (RT-PCR). The phospho-mitogen activated protein kinase (p-p38MAPK) and caspase3 protein levels were examined by Western blot. RESULTS: Proliferation was significantly increased in 1 µmol/L and 10 µmol/L groups compared with the normal control group (1.05 ± 0.05 and 1.09 ± 0.02 vs. 1.00 ± 0.03, all P < 0.05).CFBs apoptosis was significantly enhanced in 50 µmol/L and 100 µmol/L groups ((22.69 ± 2.18)% and (36.40 ± 6.80)% vs.(4.50 ± 1.08)%, all P < 0.05). Expression of Collagen I peaked in 10 µmol/L group, expression of collagen III and c-myc increased dose-dependently in proportion to increasing NE concentrations (all P < 0.05 vs. control group). The expression of p-p38MAPK and caspase3 was also significantly upregulated in a dose-dependent manner in NE groups (all P < 0.05 vs. control group). CONCLUSIONS: Low concentration NE induces CFBs proliferation and high concentration NE promotes CFBs apoptosis. p38MAPK phosphorylation may be a major mediator of NE-induced effects on CFBs.

New energy vehicles' technology innovation coordination strategy based on alliance negotiation under dual credit policy.

The development of new energy vehicles (NEVs) is one of the effective ways to alleviate carbon emissions, environmental pollution, and energy scarcity in the transportation sector. The Chinese government has innovatively proposed the "dual credit policy," but it is still a hot topic whether it can promote the NEVs' technological innovation. In this study, we construct game models and obtain the technological innovation strategies for NEVs under the dual credit policy, considering that the NEV supply chain contains one manufacturer and N suppliers. Further, we construct bargaining game models and study how to encourage manufacturers and suppliers to enhance technological innovation, realize supply chain coordination, and give the alliance strategy to maximize suppliers' profit. We found that the dual credit policy can effectively stimulate technological innovation, and the higher the credit price or technological innovation credit factor, the higher the technical level of NEVs. The findings could guide the government to adjust and revise the policy. Second, we found that the bargaining games could coordinate the NEV supply chain so that decentralized enterprises can achieve optimal technological innovation under centralized decision-making. Third, we found that suppliers can improve their profits by choosing a suitable alliance strategy under the manufacturer's different negotiating power.

Comparative effectiveness of chemotherapy in different histological types of pancreatic cancer: a PSM-based study using the SEER database.

This study aimed to compare the effectiveness of chemotherapy in different histological types of pancreatic cancer using data collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients who were diagnosed with pancreatic cancer between 2004 and 2015 were selected from the SEER database. Propensity score matching (PSM) was employed to minimize the selection bias. The Kaplan-Meier survival curves and the log-rank test were utilized to compare the overall survival (OS) and cancer-specific survival (CSS) among different groups. Of the 7,653 pancreatic cancer patients, both OS and CSS were higher in the chemotherapy group than those in the non-chemotherapy group (p < 0.001). After PSM, 2381 pairs were generated. The Kaplan-Meier survival curved indicated that both OS and CSS for pancreatic ductal adenocarcinoma (PDAC), pancreatic adenosquamous carcinoma (PASC), and pancreatic mucin-producing adenocarcinoma (PMPAC) (p < 0.001) in the chemotherapy group were superior to those in the non-chemotherapy group, while there was no significant difference in pancreatic mucinous adenocarcinoma (PMAC) (p = 0.2586). Compared with PASC and PMPAC, PDAC exhibited longer OS and CSS. The results of statistical analysis showed that PASC tumors were mainly poorly differentiated, and the majority of patients with PMPAC had distant metastasis. Chemotherapy could prolong pancreatic cancer patients' survival, especially for patients with advanced disease. PMPAC patients had a higher rate of metastasis, accompanying with the worse survival.

Does erectile dysfunction predict cardiovascular risk? A cross-sectional study of clinical characteristics in patients with erectile dysfunction combined with coronary heart disease.

Background: Erectile Dysfunction (ED) is a common sexual dysfunction in men who are unable to consistently obtain and maintain sufficient penile erection to accomplish a satisfactory sexual life. ED is currently considered to be a predictor of cardiovascular disease (CVD), but few studies have observed the association between ED and clinical features of coronary heart disease (CHD). An investigation of the association between ED and clinical characteristics of CHD was carried out using a cross-sectional study design. Methods: This cross-sectional single-center study was conducted in the Department of Cardiology and included 248 patients. Associations between patients' general information, underlying disease information, coronary heart disease information, and ED severity were statistically and analytically analyzed using SPSS 26.0 software. Patients with comparable clinical characteristics were grouped together using K-means clustering. Finally, ordered logistic regression analysis was performed for general and underlying disease information. Results: In the comparison of general data, age, education, and weekly exercise were associated with the distribution of ED severity. In the comparison of underlying disease information, the number of underlying diseases, hypertension, diabetes, hyperlipidemia, anxiety state, and depressive state were associated with the distribution of ED severity. In the comparison of CHD information, the degree of ED severity was associated with CHD subtypes, lesion sites, number of stenoses, degree of stenosis, and interventional interventions. The time from ED to CHD onset was associated with the subtypes of CHD and the number of stenoses. We clustered the main characteristics of low-risk and high-risk patients and ordered logistic regression analysis found that BMI, smoking, alcoholism, number of underlying diseases, diabetes, anxiety state, and depression state were all risk factors for CHD severity (P < 0.05); the higher the value of the above factors, the more severe the degree of CHD. Age was a protective factor for CHD severity; the younger the patient, the lower the likelihood of myocardial infarction. Conclusion: ED severity and the time from ED to CHD onset may be predictive of coronary heart disease severity. Reducing smoking and alcohol consumption, maintaining a healthy body weight, and regular physical activity are important in preventing CVD in ED patients.

Exploring the Mechanisms of Yishen Tongluo Decoction on Repairing DNA Damage in Mouse Spermatogonia Cells Based on Whole Transcriptome Sequencing.

The aim of this study was to investigate the potential mechanism through which Yishen Tongluo decoction (YSTL) repairs DNA damage caused by benzo(a)pyrene diol epoxide (BPDE) in mouse spermatocytes (GC-2). The GC-2 cells were divided randomly into the control group, BPDE group, and low-, medium-, and high-dose YSTL groups of YSTL decoction. A comet assay was used to detect the DNA fragment index (DFI) of cells in each group. Based on the DFI results, whole transcriptome sequencing was conducted, followed by trend analysis, gene ontology (GO) enrichment analysis, kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and ceRNA network analysis. Compared with the control group, the BPDE group reported a significant increase in the DNA fragmentation index (DFI) (p < .05). Compared with the BPDE group, the low-, high- and medium-dose YSTL groups had a significantly reduced DFI (p < .05). Whole-transcriptome sequencing revealed seven differentially expressed circRNAs, 203 differentially expressed miRNAs, and 3,662 differentially expressed mRNAs between the control group and the BPDE group. There was a total of 12 differentially expressed circRNAs, 204 miRNAs, and 2150 mRNAs between the BPDE group and the traditional Chinese medicine group. The pathways involved include DNA repair pathway, nucleotide excision repair pathway, base excision repair pathway, etc. The ceRNA network reported that Hmga2 was the core protein involved, novel_cir_000117 and mmu-miR-466c-3p were located upstream of Hmga2, and they were regulatory factors associated with Hmga2. Finally, we conclude that YSTL decoction may repair sperm DNA damage caused by BPDE through the novel_cir_000117-mmu-miR-466c-3p-Hmga2 pathway.

A meta-analysis on the prevalence of Charcot-Marie-Tooth disease and related inherited peripheral neuropathies.

BACKGROUND: Charcot-Marie-Tooth disease and related inherited peripheral neuropathies (CMT&RIPNs) brings great suffering and heavy burden to patients, but its global prevalence rates have not been well described. METHODS: We searched major English and Chinese databases for studies reporting the prevalence of CMT&RIPNs from the establishment of the databases to September 26, 2022. Based on the age, gender, study design, study region, and disease subtype, the included studies were correspondingly synthesized for meta-analyses on the overall prevalence and/or the subgroup analyses by using pool arcsine transformed proportions in the random-effects model. RESULTS: Of the finally included 31 studies, 21 studied the whole age population and various types of CMT&RIPNs, and the others reported specific disease subtype(s) or adult or non-adult populations. The pooled prevalence was 17.69/100,000 (95% CI 12.32-24.33) for the whole age population and significantly higher for CMT1 [10.61/100,000 (95% CI 7.06-14.64)] than for other subtypes (P' < 0.001). Without statistical significance, the prevalence seemed higher in those aged ≥ 16 or 18 years (21.02/100,000) than in those aged < 16 years (16.13/100,000), in males (22.50/100,000) than in females (17.95/100,000), and in Northern Europe (30.97/100,000) than in other regions. CONCLUSION: CMT&RIPNs are relatively more prevalent as CMT1 in the disease subtypes, and probably prevalent in older ages, males, and Northern Europe. More studies on the epidemiological characteristics of CMT&RIPNs with well-defined diagnosis criteria are needed to improve the prevalence evaluation and to arouse more attention to health care support.

Identification of m6A-associated LncRNAs as predict factors for the immune infiltration and prognosis of thyroid cancer.

OBJECTIVE: This study aims to evaluate the prognostic value of m6A-associated long noncoding RNAs (lncRNAs) and their interaction with tumour microenvironment in thyroid cancer (THCA). METHODS: The clinical and gene expression data of tumours from 502 patients with THCA and 58 adjacent normal tissues were retrieved from The Cancer Genome Atlas (TCGA)-THCA dataset. The Pearson test was utilized to identify potential m6A-associated lncRNAs (p < 0.001 and Pearson correlation coefficient > 0.4). Quantitative real-time polymerase chain reaction was performed to verify the expression levels of lncRNAs in tissues. MTT, EdU, colony formation and wound-healing assays were performed to determine the functions of m6A-associated lncRNAs in THCA cell proliferation and metastasis. RESULTS: M6A-associated lncRNAs were identified in three cluster groups. A significant survival difference was found among them, with cluster 1 patients showing worse survival. Moreover, lower immune and estimate scores were correlated to poorer prognosis, and CD8+ T cell and memory CD4+ T cell levels were increased in cluster 1. Cluster 2, with better overall survival, had high expression of PD-L1 and CTLA-4. Eleven of the m6A-associated lncRNAs were screened to establish the risk model, including AC007365.1, AC008555.1, AC040160.1, AC064807.1, AC126773.4, AL023583.1, AL512306.2, EIF2AK3-DT, LINC00667, LYPLAL1-DT and MIR181A2HG. Based on the median risk score, THCA patients were stratified into low-risk and high-risk groups. Overall survival analysis showed a dramatic difference between the two groups. qRCR was performed to verify the expression levels of lncRNA (LYPLAL1-DT, EIF2AK3-DT and MIR181A2HG) in THCA and adjacent normal tissues. Furthermore, functional experiments showed that knockdown of MIR181A2HG obviously inhibited the proliferation and migration of papillary thyroid cancer (PTC) cells in vitro, whereas LYPLAL1-DT overexpression promoted PTC cell proliferation and migration. CONCLUSIONS: Eleven of the m6A-associated lncRNAs were identified as a risk model to predict clinical outcomes and provide a novel and efficient immunotherapeutic strategy for THCA patients.Key messagesm6A-associated lncRNAs can be used to predict the clinical outcomes of thyroid cancer patients.An m6A-associated lncRNAs risk model, which can accurately evaluate the immune status and risk stratification in individual thyroid cancer patients, was established.Knockdown/overexpression of representative lncRNAs in the risk model significantly affected the proliferation and migration of papillary thyroid cancer cells.

Superhydrophilic Interconnected Biomass-Based Absorbers Toward High-Speed Evaporation for Solar Steam Generation.

Taking abundant and sustainable solar energy as the only energy source, solar-powered interface evaporation has been regarded as a promising method to alleviate the pressure of freshwater shortage. However, the uptake of clean water from brine is constantly accompanied by evaporation of water and condensation of vapor, which inevitably generates salt solid, preventing further continuous and stable evaporation. The most direct method is to fabricate a photothermal material with salt self-resistance by using the reflux of salt ions. Here, a superhydrophilic interconnected biomass carbon absorber (SBCA) is prepared by freeze-drying and carbonization, realizing strong liquid pumping, and self-blocking salt. In combination with superior broadband light absorption (94.91%), high porosity (95.9%), superhydrophilicity, and excellent thermal localization, an evaporation device with excellent evaporation rate (2.45 kg m-2 h-1 under 1 kW m-2) is successfully proposed. In the meantime, the porous skeleton and rapid water transport can enhance the diffusion of salt ions and slow down the rate of salt deposition. As a result, no salt deposition is found on the SBCA surface after continuous irradiation at 1 kW m-2 for 15 h. The design can provide a convenient and low-cost efficient strategy for solar steam generators to address clean water acquisition.

Real-Time Detection Algorithm for Kiwifruit Canker Based on a Lightweight and Efficient Generative Adversarial Network.

Disease diagnosis and control play important roles in agriculture and crop protection. Traditional methods of identifying plant disease rely primarily on human vision and manual inspection, which are subjective, have low accuracy, and make it difficult to estimate the situation in real time. At present, an intelligent detection technology based on computer vision is becoming an increasingly important tool used to monitor and control crop disease. However, the use of this technology often requires the collection of a substantial amount of specialized data in advance. Due to the seasonality and uncertainty of many crop pathogeneses, as well as some rare diseases or rare species, such data requirements are difficult to meet, leading to difficulties in achieving high levels of detection accuracy. Here, we use kiwifruit trunk bacterial canker (Pseudomonas syringae pv. actinidiae) as an example and propose a high-precision detection method to address the issue mentioned above. We introduce a lightweight and efficient image generative model capable of generating realistic and diverse images of kiwifruit trunk disease and expanding the original dataset. We also utilize the YOLOv8 model to perform disease detection; this model demonstrates real-time detection capability, taking only 0.01 s per image. The specific contributions of this study are as follows: (1) a depth-wise separable convolution is utilized to replace part of ordinary convolutions and introduce noise to improve the diversity of the generated images; (2) we propose the GASLE module by embedding a GAM, adjust the importance of different channels, and reduce the loss of spatial information; (3) we use an AdaMod optimizer to increase the convergence of the network; and (4) we select a real-time YOLOv8 model to perform effect verification. The results of this experiment show that the Fréchet Inception Distance (FID) of the proposed generative model reaches 84.18, having a decrease of 41.23 compared to FastGAN and a decrease of 2.1 compared to ProjectedGAN. The mean Average Precision (mAP@0.5) on the YOLOv8 network reaches 87.17%, which is nearly 17% higher than that of the original algorithm. These results substantiate the effectiveness of our generative model, providing a robust strategy for image generation and disease detection in plant kingdoms.

Occurrence Regionalization of Kiwifruit Brown Spot in Sichuan.

Kiwifruit brown spot caused by Corynespora cassiicola is the most significant fungal disease in Sichuan, resulting in premature defoliation, which had a significant impact on yield and fruit quality. The objective of the study was to determine the occurrence regularity and suitability of kiwifruit brown spot in Sichuan. The occurrence of the disease in the main producing region was continuously monitored, the maximum entropy (MaxEnt) model was used to predict its potential distribution, and the key environmental variables were identified using the jackknife method. The results indicated that kiwifruit brown spot was widely distributed across the entire producing region in Sichuan, predominantly affecting the variety "Hongyang". The incidence (p < 0.01) and disease index (p < 0.05) showed a significant positive correlation with the cultivar, and decreased with the altitude increasing. The average area under the ROC curve (AUC) of 10 replicates was 0.933 ± 0.012, with an accuracy of 84.44% in a field test, confirming the reliability of the predicted results. The highly suitable distribution areas of kiwifruit brown spot were mainly located in the Chengdu and Ya'an regions. The entire Panzhihua region was an unsuitable distribution area, and the entire Pujiang County and Mingshan District were highly suitable distribution areas. The key environmental variables affecting the potential distribution of kiwifruit brown spot included isothermality (24.3-33.7%), minimum temperature in August (16.3-23.6 °C), maximum temperature in July (25.5-31.2 °C), minimum temperature in June (15.6-20.9 °C), precipitation in August (158-430 mm), and average temperature in October (15.6-18.8 °C). This study provides a theoretical basis for the reasonable layout of the cultivar and the precise prevention and control of the disease.

CCNB1 is involved in bladder cancer pathogenesis and silencing CCNB1 decelerates tumor growth and improves prognosis of bladder cancer.

In search of an effective therapeutic target for bladder urothelial carcinoma (BLCA), the present study aimed to investigate the expression of cyclin B1 (CCNB1) and its putative mechanism in BLCA. BLCA sequencing data from Gene Expression Omnibus and The Cancer Genome Atlas were used to analyze expression of CCNB1 mRNA and high CCNB1 expression had a poorer prognosis compared with those with low expression. Immunohistochemistry (IHC) samples collected from the Human Protein Atlas database were analyzed for CCNB1 protein expression. Short hairpin (sh) CCNB1-transfected BLCA T24 and 5637 cells were used to investigate the effects of CCNB1 and inhibit the proliferation, migration and invasion of BLCA cells, affect the cell cycle distribution and promote apoptosis of 5637 cells. A sh-CCNB1 BLCA chicken embryo chorioallantoic membrane (CAM) transplantation model was established to observe the impacts of sh-CCNB1 on the tumorigenesis of BLCA in vivo. Analysis of sequencing data showed that CCNB1 mRNA was significantly elevated in tumor and BLCA compared with normal tissues [standardized mean difference (SMD)=1.21; 95% CI: 0.26-2.15; I²=95.9%]. IHC indicated that CCNB1 protein was localized in the nucleus and cytoplasm and was significantly increased in BLCA tumor tissues. The in vitro tests demonstrated that proliferation of T24 and 5637 cells transfected with sh-CCNB1 was significantly inhibited and cell migration and invasion ability were significantly decreased. sh-CCNB1 decreased the percentage of T24 cells in G0/G1, 5637 cells in the G0/G1 phase and S phase and increased percentage of 5637 cells in the G2/M phase and increased early apoptosis of 5637 cells. The in vivo experiments demonstrated that the mass of transplanted tumors was significantly decreased compared with the control group following silencing of CCNB1. The present results suggested that CCNB1 was involve in the development and prognosis of BLCA and silencing of CCNB1 may be a promising targeted therapy for BLCA.