CircPDIA3/miR-449a/XBP1 feedback loop curbs pyroptosis by inhibiting palmitoylation of the GSDME-C domain to induce chemoresistance of colorectal cancer.

Although oxaliplatin (OXA) is widely used in the frontline treatment of colorectal cancer (CRC), CRC recurrence is commonly observed due to OXA resistance. OXA resistance is associated with a number of factors, including abnormal regulation of pyroptosis. It is therefore important to elucidate the abnormal regulatory mechanism underlying pyroptosis. Here, we identified that the circular RNA circPDIA3 played an important role in chemoresistance in CRC. CircPDIA3 could induce chemoresistance in CRC by inhibiting pyroptosis both in vitro and in vivo. Mechanistically, RIP, RNA pull-down and co-IP assays revealed that circPDIA3 directly bonded to the GSDME-C domain, subsequently enhanced the autoinhibitory effect of the GSDME-C domain through blocking the GSDME-C domain palmitoylation by ZDHHC3 and ZDHHC17, thereby restraining pyroptosis. Additionally, it was found that the circPDIA3/miR-449a/XBP1 positive feedback loop increased the expression of circPDIA3 to induce chemoresistance. Furthermore, our clinical data and patient-derived tumor xenograft (PDX) models supported the positive association of circPDIA3 with development of chemoresistance in CRC patients. Taken together, our findings demonstrated that circPDIA3 could promote chemoresistance by amplifying the autoinhibitory effect of the GSDME-C domain through inhibition of the GSDME-C domain palmitoylation in CRC. This study provides novel insights into the mechanism of circRNA in regulating pyroptosis and providing a potential therapeutic target for reversing chemoresistance of CRC.

Genome-wide identification and expression analysis of flowering-related genes reveal putative floral induction and differentiation mechanisms in tea plant (Camellia sinensis).

The tea leaf is economically important, while reproductive growth reduce tea output. However, little is known about flowering mechanisms in tea plants. Here, we determined the approximate times of floral induction, floral transition and floral organ differentiation by morphological observation. We identified 401 and 356 flowering-related genes from the genomes of Camellia sinensis var. sinensis and Camellia sinensis var. assamica, respectively. Then, we compared the expression profiles of flowering-related genes in floriferous and oliganthous cultivars, the result showed that PRR7, GI, GID1B and GID1C expression is correlated with the floral induction; LFY, PNF and PNY expression was correlated with floral bud formation. Transcriptome analysis also showed that GI, PRR7 and GID1 were correlated with stress-induced flowering. Thus, we proposed putative mechanisms of flowering in tea plants. This study provides new insights into flowering and a theoretical basis for balancing vegetative and reproductive growth in tea plants and other economical plants.

Risk Factor Analysis in Patients Exhibiting Cerebral Microbleeds and the Correlation with Cognitive Impairment.

Objective: To identify the risk factors contributing to cerebral microbleeds (CMBs), analyze the correlation between the quantity and distribution of CMBs and overall cognitive performance, including specific cognitive domains in patients, and investigate the underlying mechanisms by which CMBs impact cognitive function. Methods: Patients diagnosed with cerebral small vessel disease were recruited between September 2022 and September 2023. Clinical baseline data were systematically gathered. The Montreal Cognitive Assessment (MoCA) was employed to evaluate patients' cognitive status. CMBs were identified via susceptibility-weighted imaging (SWI), noting their locations and quantities. Patients were categorized into two cohorts: those without CMBs and those with CMBs. This division facilitated the comparison of basic clinical data and laboratory indicators, aiming to elucidate the risk factors associated with CMBs. Within the CMBs cohort, patients were further classified based on the number of CMBs into mild, moderate, and severe groups, and according to CMBs' locations into deep, cortical-subcortical, and mixed groups. Spearman correlation analysis and ANOVA were utilized to compare the total MoCA scores, as well as scores in specific cognitive domains, across these groups. This approach enabled the analysis of the relationship between the quantity and location of CMBs and cognitive impairment. Results: Statistically significant differences were noted between patients with and without cerebral microbleeds (CMBs) regarding gender, age, hypertension, diabetes, history of cerebral infarction, history of alcohol consumption, glycosylated hemoglobin levels, low-density lipoprotein cholesterol, and homocysteine levels (p < .05). Multifactorial logistic regression analysis identified age, hypertension, diabetes, history of alcohol consumption, and elevated homocysteine as independent risk factors for the development of CMBs. Spearman correlation analysis revealed a linear correlation between the presence of CMBs and the total score of the MoCA (r = -.837, p < .001). The group with CMBs demonstrated a significant decline in visuospatial execution function and delayed recall abilities compared to the group without CMBs (p < .05). Specifically, deep CMBs were linked to impairments in visuospatial execution function, naming, attention, computational ability, language, delayed recall, and orientation (p < .05). Cortical-subcortical CMBs affected visuospatial execution function, attention, computational ability, and delayed recall ability(p < .05). Mixed CMBs impacted visuospatial execution function and naming (p < .05). Conclusion: Age, hypertension, diabetes, history of alcohol consumption, and elevated homocysteine levels are key independent risk factors for CMBs. There exists a linear relationship between the severity of CMBs and the extent of cognitive impairment. Patients with CMBs show notable deterioration in visuospatial execution function and delayed recall abilities. Furthermore, the location of CMBs influences various specific cognitive domains.

The Value of Shear Wave Elastography in the Diagnosis of Breast Cancer Axillary Lymph Node Metastasis and Its Correlation With Molecular Classification of Breast Masses.

Objective: To explore the diagnostic value of shear wave elastography examination (SWE) on axillary node metastasis (ANM) in breast cancer, this study aimed to evaluate the correlation between the SWE features and different molecular types of breast cancer, and to check the elastic modulus differences among the molecular types. Methods: Breast cancer patients from November 2020 to December 2021 were subjected to both conventional ultrasonic examination (CUE) and SWE before ultrasound-guided percutaneous biopsy or axillary lymph node dissection (ALND). We used the pathological results as the gold standard to draw the receiver operating characteristic (ROC) curve. Results: SWE outperforms CUE, but their conjunctive use is the best option. No significant correlation was found between the elastic modulus values and the molecular types of breast cancer. Conclusion: SWE can be used as an routine auxiliary method of CUE for ANM.

Influence of Ru on structure and corrosion behavior of passive film on Ti-6Al-4V alloy in oil and gas exploration conditions.

In order to investigate the influence of minor Ru on the electrochemical behaviour and structural characteristics of passive films on the surface of Ti-6Al-4V alloys under various oil and gas exploration conditions, electrochemical techniques, X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM) and corrosion simulation tests were carried out. The results revealed that the oil and gas exploration conditions had a serious impact on the electrochemical behaviour and corrosion resistance of the tested alloys. The passivation film resistance and corrosion potential of the tested titanium alloys were significantly reduced with increasing acidity and temperature. With the addition of minor ruthenium, the potential of the passive film on the Ti-6Al-4V-0.11Ru alloy surface increased because of the high surface potential of the ruthenium element. The contents of metallic ruthenium and tetravalent titanium oxide TiO2 in the surface film of the Ti-6Al-4V-0.11Ru alloy both increased with increasing temperature, which led to increase the thickness, stability, corrosion resistance and repairability of the passive film on the surface of the Ti-6Al-4V-0.11Ru alloy being better than those qualities of Ti-6Al-4V. These results were also confirmed by corrosion simulation tests.

Hydroxylated Graphene: A Promising Reinforcing Nanofiller for Nanoengineered Cement Composites.

A very low dosage of graphene oxide (GO) can enhance the mechanical durability of cement composites, but the reinforcing enhancement is highly dependent on the uniform dispersion of graphene in the matrix. Carboxylic groups at GO nanosheets have a decisive effect on GO aggregation in an alkaline cement solution because they have a strong complexation ability with aqueous Ca2+ released by cement hydration and subsequently crosslinks the adjacent graphene sheets, causing the immediate coagulation of GO. The available methods of homogeneously dispersing GO in a cement slurry cannot completely eliminate this carboxylic-crosslinking-induced GO coagulation. In this study, many hydroxyl groups were introduced onto the edge and planar nanosheets to prepare water-soluble hydroxylated graphene (HO-G) by facile ball milling. The structure of HO-G was thoroughly characterized in detail, and its dispersion behavior in pure water and Ca(OH)2 was extensively investigated. These results showed that the prepared HO-G exhibited good hydrophilicity and excellent colloidal dispersion ability against high pH and Ca2+ ions compared to GO. The effect of HO-G on the workability, mechanical strength, and chloride penetrability of a cement mortar was further studied. At a content of 0.03% by cement mass, HO-G provided 28.62 and 21.19% enhancements of compressive strength and 3.85 and 7.89% enhancements of flexural strength at 3 and 28 days, respectively, while the non-steady-state migration coefficient decreased by 31.51% compared to the reference mortar. Compared to GO, a lower dosage of HO-G exhibited a similar reinforcing effect to cement composites with little adverse impact on the fluidity of the fresh cement slurry. Moreover, the addition of HO-G could refine the pore structure, accelerate the hydration process of cement to some degree, and generate more hydration products so that the structure of the cement mortar was densified. Considering its environmentally friendly preparation, HO-G, as a promising reinforcing nanofiller, could provide a new solution to develop nanoengineered cement composites.

Pale green mutant analyses reveal the importance of CsGLKs in chloroplast developmental regulation and their effects on flavonoid biosynthesis in tea plant.

Tea cultivars with leaf color variation have attracted increasing attention in tea production and research due to their unusual appearances and appealing flavors. However, the molecular mechanism underlying this variation is little known due to the unavailability of genetic transformation and a highly complex genome. Here, a natural tea plant mutant producing pale green branches (pgb) was discovered and characterized. Ultrastructural and biochemical analyses showed that the leaves of the pgb mutant had defective chloroplast structure and significantly lower pigment content than the normal control. Comprehensive expression detection of chloroplast-development-related genes further indicated that a significant downregulation of CsGLKs in the pgb mutant likely caused the chloroplast defect. Transcriptome analyses and polyphenolic compound determination highlighted a tight correlation between photosynthesis and secondary metabolite biosynthesis in tea plant. These results provide useful information illuminating the mechanism of chloroplast development and leaf color variation in tea plant.

Soluble Myeloid Triggering Receptor Expressed on Myeloid Cell 1 Might Have More Diagnostic Value for Bacterial Ascites than C-reactive Protein.

The timely and accurate diagnosis of ascites is of great significance for early treatment and prognostication. This study explored the value of soluble myeloid triggering receptor expressed on myeloid cell 1 (sTREM-1) and C-reactive protein (CRP) for assessing ascites. A total of 133 patients with ascites who received treatment at the Affiliated Hospital of Taishan Medical University between September 2015 and September 2017 were retrospectively analyzed. The ascites in 22, 45, 33 and 33 patients were tuberculous, bacterial, tumorous, and transudative, respectively. Healthy volunteers (n=30) who received a health examination at the same hospital during the same period constituted the control group. Before treatment, both ascitic sTREM-1 and CRP showed significant differences among the ascites subgroups (P<0.001), with the highest levels in the bacterial subgroup. Serum sTREM-1 and CRP also showed significant differences among the groups. A correlation analysis showed a positive correlation between sTREM-1 and CRP. ROC curves of the bacterial subgroup showed that when the optimal cutoff point was set to 20.2, the sensitivity, specificity, positive predictive value, and negative predictive value of the serum sTREM-1 index were 0.933, 0.955, 0.914, and 0.965, respectively. sTREM-1 may provide more diagnostic value than CRP for the diagnosis of bacterial ascites.

Discovery of Plant Viruses From Tea Plant (Camellia sinensis (L.) O. Kuntze) by Metagenomic Sequencing.

The tea plant (Camellia sinensis (L.) O. Kuntze) is an economically important woody species. In this study, we collected 26 tea plant samples with typical discoloration symptoms from different tea gardens and performed metagenomic analysis based on next-generation sequencing. Homology annotation and PCR sequencing validation finally identified seven kinds of plant viruses from tea plant. Based on abundance distribution analysis, the two most abundant plant viruses were highlighted. Genetic characterization suggested that they are two novel virus species with relatively high homology to Blueberry necrotic ring blotch virus and American plum line pattern virus. We named the newly discovered viruses tea plant necrotic ring blotch virus (TPNRBV) and tea plant line pattern virus (TPLPV). Evolutionary relationship analysis indicated that TPNRBV and TPLPV should be grouped into the Blunervirus and the Ilarvirus genera, respectively. TPLPV might have same genome activation process with known ilarviruses based on sequence analysis. Moreover, specific primers for both viruses detection were designed and validated. The symptoms and ultrastructure of TPNRBV infected leaves were first recorded. Virus detections in the symptomatic and asymptomatic tissues from field plants showing tea plant necrotic ring blotch disease suggest that TPNRBV has a systemic movement feature. In summary, we first identified seven kinds of putative plant viruses by metagenomic analysis and report two novel viruses being latent pathogens to tea plant. The results will advance our understanding of tea plant virology and have significance for the genetic breeding of tea plants in the future.