Revealing the spatiotemporal brain dynamics of covert speech compared with overt speech: A simultaneous EEG-fMRI study.

Covert speech (CS) refers to speaking internally to oneself without producing any sound or movement. CS is involved in multiple cognitive functions and disorders. Reconstructing CS content by brain-computer interface (BCI) is also an emerging technique. However, it is still controversial whether CS is a truncated neural process of overt speech (OS) or involves independent patterns. Here, we performed a word-speaking experiment with simultaneous EEG-fMRI. It involved 32 participants, who generated words both overtly and covertly. By integrating spatial constraints from fMRI into EEG source localization, we precisely estimated the spatiotemporal dynamics of neural activity. During CS, EEG source activity was localized in three regions: the left precentral gyrus, the left supplementary motor area, and the left putamen. Although OS involved more brain regions with stronger activations, CS was characterized by an earlier event-locked activation in the left putamen (peak at 262 ms versus 1170 ms). The left putamen was also identified as the only hub node within the functional connectivity (FC) networks of both OS and CS, while showing weaker FC strength towards speech-related regions in the dominant hemisphere during CS. Path analysis revealed significant multivariate associations, indicating an indirect association between the earlier activation in the left putamen and CS, which was mediated by reduced FC towards speech-related regions. These findings revealed the specific spatiotemporal dynamics of CS, offering insights into CS mechanisms that are potentially relevant for future treatment of self-regulation deficits, speech disorders, and development of BCI speech applications.

Unraveling the molecular freezing behavior of water on a calcium silicate hydrate matrix.

The hydration process of cement-based materials primarily results in the formation of calcium silicate hydrate (CSH), which is crucial in deciding how long concrete will last. This study utilizes molecular dynamics simulation technology to explore the freezing behavior of pure water solutions within various calcium silicate hydrate (CSH) matrices. The investigated matrices encompass four different Ca/Si ratios. According to the simulation, as ice crystals develop close to the surface of CSH, the CSH matrix strengthens its hydrogen and ionic interactions with water molecules, which effectively prevents water molecules from crystallizing and nucleating. Consequently, these molecules compose an unfrozen water film structure that bridges between ice crystals and the CSH matrix. The research also reveals an intriguing relationship between silica chain behavior on the Ca/Si ratio and the CSH surface. Surface flaws arise as a result of the silica chains of CSH breaking into shorter segments as the Ca/Si ratio increases. These surface defects manifest as grooves on the matrix's surface, effectively capturing and retaining specific water molecules. The CSH matrix's hydrogen bonds with water molecules are weakened as a result of this process, facilitating their participation in the crystallization process, and leading to a thinner unfrozen water film thickness with an increased Ca/Si ratio. This study contributes to a greater knowledge of the performance and dependability of cement-based products by offering molecular-level insights into the freezing actions of liquids in gel pores.

Catheter ablation of atrial fibrillation in patients with left bundle branch block.

BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.

Establishment and Validation of a Risk Prediction Model for Non-Invasive Ventilation Failure After Birth in Premature Infants with Gestational Age < 32 Weeks.

OBJECTIVES: This study was performed to construct and validate a risk prediction model for non-invasive ventilation (NIV) failure after birth in premature infants with gestational age < 32 weeks. METHODS: The data were derived from the multicenter retrospective study program - Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network from Jan 2019 to Dec 2021. The subjects finally included were preterm infants using NIV after birth with gestational age less than 32 weeks and admission age within 72 h. After screening by inclusion and exclusion criteria, 1436 babies were subsequently recruited in the study, including 1235 infants in the successful NIV group and 201 infants in the failed NIV group. RESULTS: (1) Gestational age, 5 min Apgar, Max FiO2 during NIV, and FiO2 fluctuation value during NIV were selected by univariate and multivariate analysis. (2) The area under the curve of the prediction model was 0.807 (95% CI: 0.767-0.847) in the training set and 0.825 (95% CI: 0.766-0.883) in the test set. The calibration curve showed good agreement between the predicted probability and the actual observed probability (Mean absolute error = 0.008 for the training set; Mean absolute error = 0.012 for the test set). Decision curve analysis showed good clinical validity of the risk model in the training and test cohorts. CONCLUSION: This model performed well on dimensions of discrimination, calibration, and clinical validity. This model can serve as a useful tool for neonatologists to predict whether premature infants will experience NIV failure after birth.

Biochemical and Transcriptome Analysis Reveals Pigment Biosynthesis Influenced Chlorina Leaf Formation in Anoectochilus roxburghii (Wall.) Lindl.

Anoectochilus roxburghii (Wall.) Lindl is a perennial herb of the Orchidaceae family; a yellow-green mutant and a yellow mutant were obtained from the wild type, thereby providing good material for the study of leaf color variation. Pigment content analysis revealed that chlorophyll, carotenoids, and anthocyanin were lower in the yellow-green and yellow mutants than in the wild type. Transcriptome analysis of the yellow mutant and wild type revealed that 78,712 unigenes were obtained, and 599 differentially expressed genes (120 upregulated and 479 downregulated) were identified. Using the Kyoto Encyclopedia of Genes and Genomes pathway analysis, candidate genes involved in the anthocyanin biosynthetic pathway (five unigenes) and the chlorophyll metabolic pathway (two unigenes) were identified. Meanwhile, the low expression of the chlorophyll and anthocyanin biosynthetic genes resulted in the absence of chlorophylls and anthocyanins in the yellow mutant. This study provides a basis for similar research in other closely related species.

Family Integrated Care Shortens the Duration of Home Oxygen Therapy in Infants With Bronchopulmonary Dysplasia.

BACKGROUND: There have been few reports on whether family integrated care (FIC) can help premature infants with moderate to severe bronchopulmonary dysplasia (BPD) to shorten the duration of home oxygen therapy (HOT). PURPOSE: To investigate the effect of FIC on the duration of HOT in premature infants with moderate to severe BPD. METHODS: The subjects were retrospectively selected from premature infants with moderate to severe BPD in our center between June 2019 and December 2021. Patients were divided into the FIC group (n = 47) and the non-FIC group (n = 34). For univariate analysis, t test, Mann-Whitney U test, Pearson χ 2 test, or Fisher exact test was performed to explore the differences between the 2 groups. For multivariate analysis, simple and multiple linear regression was conducted to explore the effect of FIC on the duration of HOT. RESULTS: (1) The duration of HOT and length of stay after grouping were significantly shorter in the FIC group than in the non-FIC group ( P < .05). (2) The results of linear regression further revealed that FIC could significantly shorten the duration of HOT (simple linear regression, FIC [A] B : -12.709, 95% confidence interval (CI): -21.665 to -3.753; multiple linear regression, FIC [B] B : -11.419, 95% CI: -18.055 to -4.783). IMPLICATIONS FOR PRACTICE AND RESEARCH: FIC improved the optimal target oxygen saturation ratio before discharge and shortened the duration of HOT in premature infants with moderate and severe BPD. FIC should be promoted in China's neonatal intensive care units, though it puts forward new requirements for nursing education and training.

Shell Modulation of Hollow Metal Sulfide Nanocomposite for Stable Potassium Storage at Room and High Temperature.

The large size of K-ion makes the pursuit of stable high-capacity anodes for K-ion batteries (KIBs) a formidable challenge, particularly for high temperature KIBs as the electrode instability becomes more aggravated with temperature climbing. Herein, we demonstrate that a hollow ZnS@C nanocomposite (h-ZnS@C) with a precise shell modulation can resist electrode disintegration to enable stable high-capacity potassium storage at room and high temperature. Based on a model electrode, we identify an interesting structure-function correlation of the h-ZnS@C: with an increase in the shell thickness, the cyclability increases while the rate and capacity decrease, shedding light on the design of high-performance h-ZnS@C anodes via engineering the shell thickness. Typically, the h-ZnS@C anode with a shell thickness of 60 nm can deliver an impressive comprehensive performance at room temperature; the h-ZnS@C with shell thickness increasing to 75 nm can achieve an extraordinary stability (88.6 % capacity retention over 450 cycles) with a high capacity (450 mAh g-1) and a superb rate even at an extreme temperature of 60 °C, which is much superior than those reported anodes. This contribution envisions new perspectives on rational design of functional metal sulfides composite toward high-performance KIBs with insights into the significant structure-function correlation.

Bioinspired, Anticoagulative, 19 F MRI-Visualizable Bilayer Hydrogel Tubes as High Patency Small-Diameter Vascular Grafts.

The clinical patency of small-diameter vascular grafts (SDVGs) (ID < 6 mm) is limited, with the formation of mural thrombi being a major threat of this limitation. Herein, a bilayered hydrogel tube based on the essential structure of native blood vessels is developed by optimizing the relation between vascular functions and the molecular structure of hydrogels. The inner layer of the SDVGs comprises a zwitterionic fluorinated hydrogel, avoiding the formation of thromboinflammation-induced mural thrombi. Furthermore, the position and morphology of the SDVGs can be visualized via 19 F/1 H magnetic resonance imaging. The outer poly(N-acryloyl glycinamide) hydrogel layer of SDVGs provides matched mechanical properties with native blood vessels through the multiple and controllable intermolecular hydrogen-bond interactions, which can withstand the accelerated fatigue test under pulsatile radial pressure for 380 million cycles (equal to a service life of 10 years in vivo). Consequently, the SDVGs exhibit higher patency (100%) and more stable morphology following porcine carotid artery transplantation for 9 months and rabbit carotid artery transplantation for 3 months. Therefore, such a bioinspired, antithrombotic, and visualizable SDVG presents a promising design approach for long-term patency products and great potential of helping patients with cardiovascular diseases.

Prospective randomized comparison between upgraded '2C3L' vs. PVI approach for catheter ablation of persistent atrial fibrillation: PROMPT-AF trial design.

BACKGROUND: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF. STUDY DESIGN: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation.

Risk Factors for Left Ventricular Thrombus Formation in Patients with Dilated Cardiomyopathy.

BACKGROUND: Left ventricular thrombus (LVT) is a common complication of dilated cardiomyopathy (DCM), causing morbidity and mortality. METHODS: This study retrospectively analyzed patients with DCM from January 2002 to August 2020 in Beijing Anzhen Hospital. Clinical characteristics were compared between the LVT group and the age and sex 1:4 matched with the LVT absent group. The receiver operator characteristic (ROC) curve was plotted to evaluate the diagnostic value of D-dimer predicting LVT occurrence in DCM. RESULTS: A total of 3,134 patients were screened, and LVT was detected in 72 (2.3%) patients on echocardiography. The patients with LVT had higher D-dimer, fibrinogen, and lower systolic blood pressure than those without LVT. The ejection fraction (EF) was lower and left ventricular end-systolic diameter was larger in the LVT group. Severe mitral regurgitation (MR) was more common in the LVT absent groups. The prevalence of atrial fibrillation was lower in the LVT group. The ROC curve analysis yielded an optimal cut-off value of 444 ng/mL DDU (D-dimer units) for D-dimer to predict the presence of LVT. Multivariable binary logistic regression analysis revealed that EF (OR = 0.90, 95% CI = 0.86-0.95), severe MR (OR = 0.19, 95% CI = 0.08-0.48), and D-dimer level (OR = 15.4, 95% CI = 7.58-31.4) were independently associated with LVT formation. CONCLUSION: This study suggested that elevated D-dimer levels (>444 ng/mL DDU) and reduced EF were independently associated with increased risk of LVT formation. Severe MR could decrease the incidence of LVT.

Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway.

PURPOSE: To explore the potential role of signal transducer and activator of transcription 5A (STAT5A) in the metastasis of breast cancer, and its mechanism of regulation underlying. METHODS AND RESULTS: TCGA datasets were used to evaluate the expression of STAT5A in normal and different cancerous tissues through TIMER2.0, indicating that STAT5A level was decreased in breast cancer tissues compared with normal ones. Gene Set Enrichment Analysis predicted that STAT5A was associated with the activation of immune cells and cell cycle process. We further demonstrated that the infiltration of immune cells was positively associated with STAT5A level. Influorescence staining revealed the expression and distribution of F-actin was regulated by STAT5A, while colony formation assay, wound healing and transwell assays predicted the inhibitory role of STAT5A in the colony formation, migratory and invasive abilities in breast cancer cells. In addition, overexpression of the Notch3 intracellular domain (N3ICD), the active form of Notch3, resulted in the increased expression of STAT5A. Conversely, silencing of Notch3 expression by siNotch3 decreased STAT5A expression, supporting that STAT5A expression is positively associated with Notch3 in human breast cancer cell lines and breast cancer tissues. Mechanistically, chromatin immunoprecipitation showed that Notch3 was directly bound to the STAT5A promoter and induced the expression of STAT5A. Moreover, overexpressing STAT5A partially reversed the enhanced mobility of breast cancer cells following Notch3 silencing. Low expression of Notch3 and STAT5A predicted poorer prognosis of patients with breast cancer. CONCLUSION: The present study demonstrates that Notch3 inhibits metastasis in breast cancer through inducing transcriptionally STAT5A, which was associated with tumor-infiltrating immune cells, providing a novel strategy to treat breast cancer.

Proinflammatory activation of microglia in the cerebellum hyperexcites Purkinje cells to trigger ataxia.

Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.

Exosomal HSP90 induced by remote ischemic preconditioning alleviates myocardial ischemia/reperfusion injury by inhibiting complement activation and inflammation.

BACKGROUND/AIMS: The activation of the complement system and subsequent inflammatory responses are important features of myocardial ischemia/reperfusion (I/R) injury. Exosomes are nanoscale extracellular vesicles that play a significant role in remote ischemic preconditioning (RIPC) cardioprotection. The present study aimed to test whether RIPC-induced plasma exosomes (RIPC-Exo) exert protective effects on myocardial I/R injury by inhibiting complement activation and inflammation and whether exosomal heat shock protein 90 (HSP90) mediates these effects. METHODS: Rat hearts underwent 30 min of coronary ligation followed by 2 h of reperfusion. Plasma exosomes were isolated from RIPC rats and injected into the infarcted myocardium immediately after ligation. Sixty rats were randomly divided into Sham, I/R, I/R + RIPC-Exo (50 µg/µl), and RIPC-Exo + GA (geldanamycin, 1 mg/kg, administration 30 min before ligation) groups. Cardiomyocyte apoptosis, the release of myocardial markers (LDH, cTnI and CK-MB), infarct size, the expression of HSP90, complement component (C)3, C5a, c-Jun N-terminal kinase (JNK), interleukin (IL)-1ß, tumor necrosis factor (TNF)-alpha and intercellular adhesion molecule -1 (ICAM-1) were assessed. RESULTS: RIPC-Exo treatment significantly reduced I/R-induced cardiomyocyte apoptosis, the release of myocardial markers (LDH, cTnI and CK-MB) and infarct size. These beneficial effects were accompanied by decreased C3 and C5a expression, decreased inflammatory factor levels (IL-1ß, TNF-α, and ICAM-1), decreased JNK and Bax, and increased Bcl-2 expression. Meanwhile, the expression of HSP90 in the exosomes from rat plasma increased significantly after RIPC. However, treatment with HSP90 inhibitor GA significantly reversed the cardioprotection of RIPC-Exo, as well as activated complement component, JNK signalling and inflammation, indicating that HSP90 in exosomes isolated from the RIPC was important in mediating the cardioprotective effects during I/R. CONCLUSION: Exosomal HSP90 induced by RIPC played a significant role in cardioprotection against I/R injury, and its function was in part linked to the inhibition of the complement system, JNK signalling and local and systemic inflammation, ultimately alleviating I/R-induced myocardial injury and apoptosis by the upregulation of Bcl-2 expression and the downregulation of proapoptotic Bax.

Natural compound fraxinellone ameliorates intestinal fibrosis in mice via direct intervention of HSP47-collagen interaction in the epithelium.

Intestinal fibrosis is a common complication of inflammatory bowel disease. There is still a lack of effective drugs for the prevention or treatment of intestinal fibrosis. Heat shock protein 47 (HSP47) plays a key role in the development of intestinal fibrosis. In this study we investigated the therapeutic potential and underlying mechanisms of fraxinellone, a degraded limonoid isolated from the root bark of Dictamnus dasycarpus, in the treatment of intestinal fibrosis. Intestinal fibrosis was induced in mice by dextran sodium sulfate (DSS) treatment. DDS-treated mice were administered fraxinellone (7.5, 15, 30 mg·kg-1·d-1, i.g.) for 45 days. We showed that fraxinellone administration dose-dependently alleviated DSS-induced intestinal impairments, and reduced the production of intestinal fibrosis biomarkers such as α-smooth muscle actin (SMA), collagen I, hydroxyproline, fibronectin and laminin, and cytokines such as TGF-ß, TNF-α and IL-ß. We then established in vitro intestinal fibrosis cell models in SW480 and HT-29 cells, and demonstrated that treatment with fraxinellone (3, 10, 30 µM) significantly relieved TGF-ß-induced fibrosis responses by inhibiting the TGF-ß/Smad2/3 signaling pathway. Molecular docking suggested that the fraxinellone might disrupt the interaction between HSP47 and collagen, which was confirmed by coimmunoprecipitation experiments. SPR analysis showed that fraxinellone had a high affinity for HSP47 with a Kd value of 3.542 × 10-5 M. This study provides a new example of HSP47-collagen intervention by a natural compound and has important implications for the clinical treatment of inflammation-induced issue fibrosis.

Adenoid cystic carcinoma in children and young adults: A clinicopathological study of 12 cases.

OBJECTIVE: To investigate the clinicopathological characteristics, immunoprofile, and molecular alterations of adenoid cystic carcinoma (ACC) in children and young adults. MATERIALS AND METHODS: Twelve cases of ACC were included. MYB, MYBL1, Ki-67, type IV Collagen, Laminin, and LAMB1 expression were detected by immunohistochemistry. MYB and MYBL1 rearrangements were detected by fluorescence in situ hybridization. RESULTS: Among 12 patients, four were female and eight were male. Seven cases (58.3%) located in major salivary glands and eight cases (66.7%) were classified as Grade I. Ten tumors (83.3%) had collagenous and hyalinized stroma. MYB was positive in 83.3% cases, and the average Ki-67 labeling index (LI) was 8.3%. LAMB1, type IV Collagen, and Laminin were positive in 91.7%, 66.7%, and 58.3% cases, respectively. Besides, three out of eight tumors had MYB rearrangement. Cases without MYB rearrangement were negative for MYBL1 expression and MYBL1 rearrangement. The average follow-up time was 91.8 months. Four patients had recurrent diseases. CONCLUSIONS: ACC in children and young adults was seen more frequently in males and major salivary glands. Most cases had ECM and hyaline stroma. Grade III tumors, higher Ki-67 LI, negative expression of type IV Collagen, and Laminin showed a tendency of higher recurrence rate.

First report of Colletotrichum gloeosporioides causing anthracnose on grapevine (Vitis vinifera) in Shaanxi province, China.

Grape anthracnose caused by Colletotrichum spp. is an economically important disease in most vineyards during rainy and humid weather. In June 2021, widespread anthracnose was observed in leaves of Vitis vinifera cv. Red Globe in Yangling city (latitude = 34.28, longitude = 108.07), Shaanxi Province. Diseased plants exhibited circular brown necrotic lesions with yellow borders in young leaves (Fig. 1A). Approximately 80% of the 75 grape plants showed disease symptoms that were consistent with those previously reported for anthracnose on grape caused by C. acutatum, C. gloeosporioides, and C. viniferum (Hong et al. 2008; Oo and Oh 2017). To isolate the pathogen, ten diseased leaves were collected. Small pieces (0.5 mm × 0.5 mm) of symptomatic tissue were surface sterilized with 75% alcohol for 30 s, transferred to 4% NaClO for 2 min, and then washed twice with sterile distilled water. The pathogen was isolated and cultured on potato dextrose agar (PDA) at 25 °C with a 12 h light/dark photoperiod. Hyphal tips of the isolate were transferred to fresh PDA after 1 day. Acervuli were formed after 15 days on PDA. The colonies were single-spored to obtain pure cultures. Pure cultures on PDA appear white to grey, and the reverse of the colonies was olive gray or yellowish white (Fig. 1B, C). Conidia were single-celled, hyaline, straight cylindrical with ends rounded, and measured 12.50 to 17.78 µm (length) (mean=15.19 µm, n=50) × 3.66 to 5.82 µm (width) (mean=4.48 µm, n=50) (Fig. 1D). The morphological characteristics matched the previous descriptions of C. gloeosporioides by Sawant et al. (2012). For molecular identification, genomic DNA was extracted from isolate YLRG13, and the actin (ACT), internal transcribed spacer (ITS), and beta-tubulin (TUB2) were amplified using the primer pairs ACT-512F/ACT-783R (Carbone and Kohn 1999), ITS1F/ITS4 (White et al. 1990), and T1/T2 (O' Donnell and Cigelnik 1997), respectively. The ACT (OQ031183 and MZ686707), ITS (OP999326 and MZ669974), and TUB2 (OQ031184 and MZ686708) nucleotide sequences of isolates YLRG5 and YLRG13 were deposited in GenBank. BLASTn showed 99 to 100% similarity with C. gloeosporioides. Neighbor-joining trees based on the three genes was constructed using PAUP version 4.0b10. The results showed the isolated YLRG5 and YLRG13 from V. vinifera was closely related to C. gloeosporioides with high bootstrap values (Fig. S2). Pathogenicity testing was performed with isolate YLRG13 by 10 µL conidial suspension (4×108 conidia/ml) on the surfaces of five wounded detached leaves of six-year-old Vitis vinifera cv. Red Globe. Sterile distilled water was used as a control. Inoculated plants were placed in a humid chamber at 25 °C. Conidial germination was observed at 24 hours post-inoculation (Fig. S1E). Four days after inoculation, typical anthracnose symptoms developed on inoculated grape leaves (Fig. S1F). No symptoms were observed on the controls. The fungus reisolated from the symptomatic grape leaves showed the same morphological characteristics of the inoculated isolate, fulfilling Koch's postulates. To our knowledge, this is the first report of grape anthracnose caused by C. gloeosporioides in Northwestern of China. C. gloeosporioides was reported causing anthracnose on a wide variety of horticultural crops, such as almond, avocado, apple, banana, cashew, citrus, cucumber, grape, guava, mango, onion, papaya, passion fruit, pepper, strawberry, tomato, and watermelon (Sharma and Kulshrestha 2015), suggesting the potential cross-infection between grape and other horticultural crops.

Oral epithelial dysplasia and aphthous ulceration in a patient with ulcerative colitis: a case report.

BACKGROUND: Ulcerative colitis is a chronic inflammatory disease with apparent extraintestinal manifestations, including in the oral cavity. Oral epithelial dysplasia, an exclusive histopathological diagnosis that is used to predict malignant transformation, has never been reported with ulcerative colitis. Herein, we report a case with ulcerative colitis that was diagnosed via extraintestinal manifestations of oral epithelial dysplasia and aphthous ulceration. CASE PRESENTATION: A 52-year-old male suffering from ulcerative colitis came to our hospital complaining of pain on his tongue with a history of 1 week. Clinical examination revealed multiple painful oval ulcers on the ventral surfaces of the tongue. Histopathological examination indicated ulcerative lesion and mild dysplasia in the adjacent epithelium. Direct immunofluorescence demonstrated negative staining along the junction of the epithelium and lamina propria. Immunohistochemical staining with Ki-67, p16, p53 and podoplanin was used to rule out the reactive cellular atypia to inflammation and ulceration of the mucosa. A diagnosis of aphthous ulceration and oral epithelial dysplasia was made. The patient was treated with mouthwash (composed of lidocaine, gentamicin and dexamethasone) and triamcinolone acetonide oral ointment. Oral ulceration healed after one week of treatment. At the 12-month follow-up, minor scarring was observed on the right ventral surface of the tongue, and the patient felt no discomfort in the oral mucosa. CONCLUSION: Oral epithelial dysplasia might also occur in patients with ulcerative colitis despite the low incidence, which should broaden the understanding of oral manifestations of ulcerative colitis.

A large-cohort study of 2971 cases of epulis: focusing on risk factors associated with recurrence.

BACKGROUND: To analyze the clinicopathological features of different histological subtypes of epulis, and evaluate the risk factors associated with recurrence. MATERIALS AND METHODS: A retrospective study including 2971 patients was performed. The patients' sex, age, location, size, histological subtypes, recurrence information, oral hygiene habits, periodontitis symptoms and smoking history were retrieved from the patient medical records and follow-up information. RESULTS: Among the 2971 cases, focal fibrous hyperplasia (FFH) was the most common lesion (60.92%), followed by peripheral ossifying fibroma (POF) (29.32%), pyogenic granuloma (PG) (8.08%) and peripheral giant cell granuloma (PGCG) (1.68%). The peak incidence of epulis was in the third and fourth decade of life, with a mean age of 45.55 years. Female predominance was found in all types of lesions with a female to male ratio of 1.71:1. PG had the highest recurrence rate (17.18%), followed by POF (12.98%), FFH (9.55%) and PGCG (8.82%). Histological subtypes were significantly correlated with the recurrence of epulis (P = 0.013). Regular supportive periodontal therapy (P = 0.050) had a negative correlation with recurrence, whereas symptoms of periodontitis (P < 0.001) had a positive correlation with the recurrence of epulis. CONCLUSIONS: Controlling the periodontal inflammation and regular supportive periodontal therapy might help reduce the recurrence of epulis.

[CiteSpace knowledge map of research status and trends of Croci Stigma].

This study retrieved Croci Stigma related literature from CNKI, Wanfang, VIP, and Web of Science database, and used bibliometrics and CiteSpace 6.1.R2 software to analyze the published Croci Stigma related articles in Chinese and English from 2000 to 2022. The authors, research institutions, and keywords were visualized and analyzed, and the current status and development trend of Croci Stigma research was summarized by combining the information extraction methods. A total of 1 846 Chinese articles and 2 703 English articles were screened out and included. The results showed a generally steady increase in the number of Croci Stigma related articles. The results of the visualization analysis showed that there were more collaborations between researcher teams and major research institutions in English articles than Chinese articles. The Chinese articles was mainly published by China Pharmaceutical University, and most of the inter-institutional collaborations occurred in neighboring regions. The English articles was mainly published by Iranian institutions, and most of the cooperation occurred within the country, with less transnational cooperation. Keywords analysis showed that the research on Croci Stigma was mainly focused on chemical compositions, pharmacological effects, mechanisms, quality control, etc. It was predicted that the future research hotspots of Croci Stigma would mainly focus on pharmacological mechanism and clinical efficacy. The current research related to Croci Stigma still needs to be developed, cooperation should be strengthened, and more in-depth research should be conducted.

TNF-α/anti-TNF-α drugs and its effect on pregnancy outcomes.

Pregnancy is a complex biological process. The establishment and maintenance of foetal-maternal interface are pivotal events. Decidual immune cells and inflammatory cytokines play indispensable roles in the foetal-maternal interface. The disfunction of decidual immune cells leads to adverse pregnancy outcome. Tumour necrosis factor (TNF)-α, a common inflammatory cytokine, has critical roles in different stages of normal pregnancy process. However, the relationship between the disorder of TNF-α and adverse pregnancy outcomes, including preeclampsia (PE), intrauterine growth restriction (IUGR), spontaneous abortion (SA), preterm birth and so on, is still indefinite. In this review, we thoroughly reviewed the effect of TNF-α disorder on pathological conditions. Moreover, we summarized the reports about the adverse pregnancy outcomes (PE, IUGR, SA and preterm birth) of using anti-TNF-α drugs (infliximab, etanercept and adalimumab, certolizumab and golimumab) currently in the clinical studies. Overall, IUGR, SA and preterm birth are the most common adverse pregnancy outcomes of anti-TNF-α drugs. Our review may provide insight for the immunological treatment of pregnancy-related complication, and help practitioners make informed decisions based on the current evidences.