Identification and virus-induced gene silencing (VIGS) analysis of methyltransferase affecting tomato (Solanum lycopersicum) fruit ripening.

MAIN CONCLUSION: Six methyltransferase genes affecting tomato fruit ripening were identified through genome-wide screening, VIGS assay, and expression pattern analysis. The data provide the basis for understanding new mechanisms of methyltransferases. Fruit ripening is a critical stage for the formation of edible quality and seed maturation, which is finely modulated by kinds of factors, including genetic regulators, hormones, external signals, etc. Methyltransferases (MTases), important genetic regulators, play vital roles in plant development through epigenetic regulation, post-translational modification, or other mechanisms. However, the regulatory functions of numerous MTases except DNA methylation in fruit ripening remain limited so far. Here, six MTases, which act on different types of substrates, were identified to affect tomato fruit ripening. First, 35 MTase genes with relatively high expression at breaker (Br) stage of tomato fruit were screened from the tomato MTase gene database encompassing 421 genes totally. Thereafter, six MTase genes were identified as potential regulators of fruit ripening via virus-induced gene silencing (VIGS), including four genes with a positive regulatory role and two genes with a negative regulatory role, respectively. The expression of these six MTase genes exhibited diverse patterns during the fruit ripening process, and responded to various external ripening-related factors, including ethylene, 1-methylcyclopropene (1-MCP), temperature, and light exposure. These results help to further elaborate the biological mechanisms of MTase genes in tomato fruit ripening and enrich the understanding of the regulatory mechanisms of fruit ripening involving MTases, despite of DNA MTases.

Specific lineage transition of tumor-associated macrophages elicits immune evasion of ascitic tumor cells in gastric cancer with peritoneal metastasis.

BACKGROUND: Gastric cancer with peritoneal metastasis (PM-GC), recognized as one of the deadliest cancers. However, whether and how the tumor cell-extrinsic tumor microenvironment (TME) is involved in the therapeutic failure remains unknown. Thus, this study systematically assessed the immunosuppressive tumor microenvironment in ascites from patients with PM-GC, and its contribution to dissemination and immune evasion of ascites-disseminated tumor cells (aDTCs). METHODS: Sixty-three ascites and 43 peripheral blood (PB) samples from 51 patients with PM-GC were included in this study. aDTCs in ascites and circulating tumor cells (CTCs) in paired PB were immunophenotypically profiled. Using single-cell RNA transcriptional sequencing (scRNA-seq), crosstalk between aDTCs and the TME features of ascites was inspected. Further studies on the mechanism underlying aDTCs-immune cells crosstalk were performed on in vitro cultured aDTCs. RESULTS: Immune cells in ascites interact with aDTCs, prompting their immune evasion. Specifically, we found that the tumor-associated macrophages (TAMs) in ascites underwent a continuum lineage transition from cathepsinhigh (CTShigh) to complement 1qhigh (C1Qhigh) TAM. CTShigh TAM initially attracted the metastatic tumor cells to ascites, thereafter, transitioning terminally to C1Qhigh TAM to trigger overproliferation and immune escape of aDTCs. Mechanistically, we demonstrated that C1Qhigh TAMs significantly enhanced the expression of PD-L1 and NECTIN2 on aDTCs, which was driven by the activation of the C1q-mediated complement pathway. CONCLUSIONS: For the first time, we identified an immunosuppressive macrophage transition from CTShigh to C1Qhigh TAM in ascites from patients with PM-GC. This may contribute to developing potential TAM-targeted immunotherapies for PM-GC.

Multiple Physiological and Biochemical Functions of Ascorbic Acid in Plant Growth, Development, and Abiotic Stress Response.

Ascorbic acid (AsA) is an important nutrient for human health and disease cures, and it is also a crucial indicator for the quality of fruit and vegetables. As a reductant, AsA plays a pivotal role in maintaining the intracellular redox balance throughout all the stages of plant growth and development, fruit ripening, and abiotic stress responses. In recent years, the de novo synthesis and regulation at the transcriptional level and post-transcriptional level of AsA in plants have been studied relatively thoroughly. However, a comprehensive and systematic summary about AsA-involved biochemical pathways, as well as AsA's physiological functions in plants, is still lacking. In this review, we summarize and discuss the multiple physiological and biochemical functions of AsA in plants, including its involvement as a cofactor, substrate, antioxidant, and pro-oxidant. This review will help to facilitate a better understanding of the multiple functions of AsA in plant cells, as well as provide information on how to utilize AsA more efficiently by using modern molecular biology methods.

Switchable Pickering Emulsions Stabilized via Synergistic Nanoparticles-Superamphiphiles Effects and Rapid Response to CO2/N2.

A CO2/N2-responsive emulsion provides milder reaction conditions, nontoxicity, and economic feasibility compared to other switchable surfactants. In this study, CO2/N2-responsive pickering emulsions were fabricated by using a compounded dispersion containing SiO2 nanoparticles (NPs) and superamphiphiles as the emulsifying agents. The synergistic effects of the SiO2 NPs and superamphiphiles significantly stabilized the emulsion at all of the tested concentrations and prevented complete phase separation of oil and water. The electrostatic interaction between the SiO2 NPs and superamphiphiles was disrupted after bubbling with CO2 for 30 s, resulting in the breaking of the emulsion. However, the dispersion recovered its interfacial activity after the introduction of N2 and again emulsified the emulsion. This reversible switching behavior was validated through three consecutive cycles of bubbling CO2/N2. The protonation and deprotonation of the SiO2 NPs and superamphiphiles in response to CO2/N2 facilitated reversible assembly and disassembly, which enabled the switching of the emulsions between inactive and active forms. The novel highly stable Pickering emulsions demonstrated rapid demulsification and emulsification in response to CO2/N2 and are promising for a wide range of applications.

Abnormal functional connectivity of the core olfactory network in patients with chronic rhinosinusitis accompanied by olfactory dysfunction.

Objective: To review and analyze the functional connectivity (FC) abnormalities in the brain olfactory network (ON) of patients with chronic rhinosinusitis with olfactory dysfunction (CRSwOD) and explore the relationship between these FC abnormalities and olfactory dysfunction, providing clues to the neurophysiological mechanisms underlying CRSwOD. Methods: FC analysis on the ON of patients with CRSwOD and patients with chronic rhinosinusitis without olfactory dysfunction (CRSsOD) identified the regions of the ON with abnormal FC in CRSwOD patients, and the correlation between abnormal FC and clinical scales for chronic rhinosinusitis was analyzed. Results: (1) Compared with the CRSsOD group, CRSwOD patients showed decreased FC between the bilateral orbitofrontal cortex (OFC) and the right middle frontal gyrus, (2) Receiver operating characteristic (ROC) curve analysis revealed that the FC value between the right middle frontal gyrus and the left OFC (area under the curve (AUC) = 0.852, sensitivity: 0.821, specificity: 0.800, p < 0.001) was more capable of distinguishing whether CRS patients may have olfactory dysfunction than the FC value between the right middle frontal gyrus and the right OFC (AUC = 0.827, sensitivity: 0.893, specificity: 0.667, p < 0.001), and (3) Lund-Kennedy scores were positively correlated with the FC values between the right middle frontal gyrus and the left OFC (r = 0.443, p < 0.018). Lund-Mackay scores were also positively correlated with the FC values between the right middle frontal gyrus and the left OFC (r = 0.468, p < 0.012). Questionnaire of Olfactory Disorders-Negative Statements scores were negatively correlated with the FC values between the right middle frontal gyrus and the left OFC (r = -0.481, p < 0.001). Conclusion: Persistent nasal inflammation affects the FC between the middle frontal gyrus and the OFC, which may serve as a potential imaging marker for identifying CRSwOD. The severity of nasal inflammation and olfactory damage is closely related to the FC between the middle frontal gyrus and OFC, and the abnormal changes in this FC can be used to explain the neurophysiological mechanisms behind the occurrence of olfactory dysfunction in patients.

Decreased Functional Connectivity of the Core Pain Matrix in Herpes Zoster and Postherpetic Neuralgia Patients.

The purpose of this study was to explore the resting-state functional connectivity (FC) changes among the pain matrix and other brain regions in herpes zoster (HZ) and postherpetic neuralgia (PHN) patients. Fifty-four PHN patients, 52 HZ patients, and 54 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. We used a seed-based FC approach to investigate whether HZ and PHN patients exhibited abnormal FC between the pain matrix and other brain regions compared to HCs. A random forest (RF) model was constructed to explore the feasibility of potential neuroimaging indicators to distinguish the two groups of patients. We found that PHN patients exhibited decreased FCs between the pain matrix and the putamen, superior temporal gyrus, middle frontal gyrus, middle cingulate gyrus, amygdala, precuneus, and supplementary motor area compared with HCs. Similar results were observed in HZ patients. The disease durations of PHN patients were negatively correlated with those aforementioned impaired FCs. The results of machine learning experiments showed that the RF model combined with FC features achieved a classification accuracy of 75%. Disrupted FC among the pain matrix and other regions in HZ and PHN patients may affect multiple dimensions of pain processing.

Aberrant functional and causal connectivity of the amygdala in herpes zoster and post-herpetic neuralgia patients.

OBJECTIVE: Resting-state functional magnetic resonance imaging (rs-fMRI) and Granger causality analysis (GCA) were used to observe the characteristics of amygdala and whole-brain effect connections in patients with herpes zoster (HZ) and post-herpetic neuralgia (PHN) and to determine their relationship with clinical features. METHODS: Rs-fMRI scans were performed on 50 HZ; 50 PHN; and 50 age-, sex- and education-year-matched healthy controls (HCs). Bilateral amygdala subregions were used as seeds for functional connectivity (FC). GCA was used to analyze the effective connection of brain regions that were significantly different among groups. Then, the correlation between FC, and GCA values and clinical indices was investigated. RESULTS: PHN had impaired FC between the amygdala subregion with the putamen, cortex, anterior cingulate cortex (ACC) to HCs and reduced FC of medial amygdala (MeA) with the parieto-occipital lobe and motor cortex to HZ; HZ had reduced FC of the lateral amygdala (LA) with the insula to HCs. GCA values from the bilateral LA to the bilateral ACC, left MeA to the bilateral ACC and left putamen, and right ACC to the bilateral MeA were reduced in PHN patients compared to HCs. Compared with HCs, the GCA values from the left MeA to the left ACC and right putamen were reduced in HZ. The GCA values from the amygdala subregion to the ACC were positively correlated with HAMA or HAMD scores in PHN. CONCLUSION: PHN showed reduced FC between the amygdala subregions and cortico-putamen and decreased effective connectivity from the amygdala subregion to the ACC and putamen. ADVANCES IN KNOWLEDGE: HZ and PHN patients had significant changes in effective connectivity in brain regions, including diverse functional areas emanating from and projecting to the amygdala. The current findings will provide a new perspective for understanding the neuropathophysiological mechanism HZ and PHN.

Regional homogeneity alterations of resting-state functional magnetic resonance imaging of chronic rhinosinusitis with olfactory dysfunction.

Objectives: The aim of this study was to assess the brain functional changes of patients with chronic rhinosinusitis with olfactory dysfunction (CRSwOD) using regional homogeneity (ReHo) of resting-state functional magnetic resonance imaging (MRI) scans, and to better explain the occurrence and development of olfactory decline in patients with chronic sinusitis provides a new idea for the study of more advanced olfactory therapy modalities. Methods: A total of 28 CRSwOD patients, 24 patients with CRS without olfactory dysfunction (CRSsOD), and 25 healthy controls (HCs) were recruited. All subjects underwent olfactory testing, clinical and brief psychological assessments, and MRI scans. A two-sided two-sample t test with AlphaSim correction (voxel-p < 0.001, cluster size >54 voxels) was used to detect differences between CRSwOD, CRSsOD, and HC groups. Results: Compared with HCs, the ReHo values in traditional olfactory regions (e.g., parahippocampal gyrus (PHG), hippocampal, olfactory cortex) were increased, and ReHo values in the frontal gyrus, middle temporal gyrus, precuneus, and posterior cingulate gyrus were decreased in CRSwOD patients. The ReHo values in the precuneus and posterior cingulate gyrus of CRSwOD patients were negatively correlated with Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) scores. Compared with CRSsOD patients, the ReHo values in cerebellar regions were increased and those in the inferior temporal gyrus, precuneus, postcentral, and paracentral gyrus were decreased in CRSwOD patients. The receiver operating characteristic (ROC) curve showed that the mean ReHo values significantly differed between the CRSwOD and CRSsOD groups. Conclusion: Synchronization of regional brain activity in the regions of the secondary olfactory cortex orbitofrontal cortex (OFC), temporal gyrus, precuneus, and cerebellum may be closely related to the development of olfactory dysfunction. Precuneus and posterior cingulate gyrus may be critical brain areas of action for emotional dysfunction in CRSwOD patients.

Greater functional connectivity between the ventral frontal cortex and occipital cortex in herpes zoster patients than post-herpetic neuralgia patients.

OBJECTIVE: This study aimed to compare whole brain network between herpes zoster (HZ) patients and post-herpetic neuralgia (PHN) patients, as well as to investigate the associations between whole brain network changes and pain intensity and the accuracy of classifying between different types of pain. METHODS: PHN patients (n = 50) and HZ patients (n = 50) and healthy controls (HCs) (n = 50) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Functional connectivity and global and local graph theory metrics were calculated by using Dosenbach-160 atlas. The relationship between neuroimaging indicators and clinical scales was evaluated using correlation analysis, and receiver operating characteristic (ROC) curves evaluated the feasibility of classifying PHN and HZ patients using specific neuroimaging indicators. RESULTS: (1) 10 greater average connectivities were found in HZ group among the default mode, frontoparietal, cingulo-opercular, sensorimotor, occipital networks (ONs), and cerebellum (p < 0.001). (2) HZ patients exhibited higher global efficiency than those in the PHN and HCs (t = 2.178, p = 0.038). (3) Multiple linear regression analyses indicated that functional connectivity between the ventral frontal cortex in the cingulo-opercular network and the occipital gyrus in the ON influenced the visual analog score pain scores (ß = 4.273; p = 0.004). CONCLUSION: The variation of functional connectivity between ventral frontal cortex in the cingulo-opercular network and occipital gyrus in the ON may be a robust neuroimaging marker of the transition from HZ to PHN patients. ADVANCES IN KNOWLEDGE: Whole-brain network analysis may be effective in distinguishing HZ and PHN patients and predicting pain intensity.

Altered White Matter Microstructure in Herpes Zoster and Postherpetic Neuralgia Determined by Automated Fiber Quantification.

This study aimed to explore changes in the white matter microstructure in herpes zoster (HZ) and postherpetic neuralgia (PHN) patients and to estimate the correlation of these changes with clinical data. Diffusion tensor imaging (DTI) data were collected from 33 HZ patients, 32 PHN patients, and 35 well-matched healthy controls (HCs). Subsequently, these data were analyzed by automated fiber quantification (AFQ) to accurately locate alterations in the white matter microstructure. Compared with HCs, HZ and PHN patients both showed a wide range of changes in the diffusion properties of fiber tracts. HZ patients exhibited changes primarily in the left superior longitudinal fasciculus (SLF), whereas PHN patients predominantly exhibited changes in the left inferior fronto-occipital fasciculus. The bilateral SLF and the left corticospinal tract were altered in the PHN patients compared with HZ patients. In addition, PHN patients showed a trend toward more expansive white matter alterations compared with those observed in HZ patients; additionally, in PHN patients, changes in the left cingulum cingulate were significantly correlated with changes in emotion and the duration of disease. These findings may help to elucidate the transformation from HZ to PHN and provide new ideas regarding the reasons for intractable neuropathic pain in PHN.

CFO Gender, Corporate Risk-Taking, and Information Disclosure Violations.

The sex ratio at birth in China exhibits a major occurrence of "missing women" due to the high son preference in Chinese culture. Clearly, the large gender discrepancy in China can be explained not only by ethical, moral, or social fairness theories but also by the economic benefits of women's particular abilities, experiences, and talents. This article examines the influence of female chief financial officers (CFOs) on information disclosure violations in order to highlight women's positive contributions. Our data imply that having a female CFO can dramatically lower the number of companies that fail to disclose information. The results are strong after controlling endogeneity with propensity score matching, Heckman's two-stage self-selection model, and CFO change, as well as controlling the gender of the chairman and chief executive officer, utilizing different study periods, and using exogenous shock. We further examined the moderate effects of CFO power and external monitoring, and we found that CFO power magnifies the negative effect of female CFO on violations; the more the power, the more the negative effect of female CFO on violations. We also found that when the firm has effective external monitoring, there are fewer future infractions of information disclosure.