The WUSCHEL-related homeobox transcription factor CsWOX3 negatively regulates fruit spine morphogenesis in cucumber (Cucumis sativus L.).

Cucumber (Cucumis sativus L.) is a widely cultivated crop with rich germplasm resources, holding significant nutritional value. It also serves as an important model for studying epidermal cell fate and sex determination. Cucumbers are covered with multicellular and unbranched trichomes, including a specific type called spines found on the surface of the fruit. The presence and density of these fruit spines determine the visual quality of cucumber fruits. However, the key regulatory genes and mechanisms underlying cucumber fruit spine development remain poorly understood. In this study, we identified a WUSCHEL-related homeobox (WOX) family gene CsWOX3, which functioned as a typical transcriptional repressor and played a negative role in fruit spine development. Spatial-temporal expression analysis revealed that CsWOX3 exhibited a relatively high expression level in the cucumber female floral organs, particularly in the fruit exocarp. Knockout of CsWOX3 using CRISPR/Cas9 resulted in a significant 2-to-3-fold increase in the diameter of fruit spines base, while overexpression led to a 17% decrease in the diameter compared to the wild-type. A SQUAMOSA PROMOTER BINDING PROTEIN-LIKE transcription factor CsSPL15 could directly bind and activate the expression of CsWOX3, thereby suppressing the expression of downstream auxin-related genes, such as CsARF18. Additionally, the RING-finger type E3 ubiquitin ligase CsMIEL1-like interacted with the HD domain of CsWOX3, which might result in the ubiquitination and subsequent alteration in protein stability of CsWOX3. Collectively, our study uncovered a WOX transcription factor CsWOX3 and elucidated its expression pattern and biological function. This discovery enhances our comprehension of the molecular mechanism governing cucumber fruit spine morphogenesis.

Effect of salt substitute and antihypertensive medications among high cardiovascular risk patients: A sub-study of Salt Substitute and Stroke Study (SSaSS).

The relationship between the differential protective effect of salt substitute between hypertensive and normotensive individuals and the use of cardiovascular medications remains unclear. This study involved 4211 individuals with a history of stroke or hypertension who participated in the Salt Substitute and Stroke Study (SSaSS) from 120 villages in Shanxi Province. The aim of this study was to investigate the differences in major adverse cardiovascular events and blood pressure changes between the salt substitute and the regular salt group in the subgroups of participants taking different antihypertensive medications. Mixed models were employed and adjusted for the cluster effect (village) and potential confounding variables. During the average follow-up period of 4.66 years, a significantly protective effect of salt substitute on reducing the risk of cardiovascular events was observed in the participants who taking antihypertensive medications (rate ratio: 0.81, 95% CI: 0.68 to 0.95. p = 0.011), whereas no significant effect in participants not taking antihypertensive medications (rate ratio: 0.91, 95% CI: 0.62 to 1.32, p = 0.612). Significant effects to lower systolic blood pressure of the salt substitutes were observed in the participants who took different antihypertensive medications. This study emphasized that the use of salt substitutes might enhance the efficacy of anti-hypertensive medications in lowering blood pressure and reducing the risk of adverse cardiovascular events.

Adenine base editing-mediated exon skipping restores dystrophin in humanized Duchenne mouse model.

Duchenne muscular dystrophy (DMD) affecting 1 in 3500-5000 live male newborns is the frequently fatal genetic disease resulted from various mutations in DMD gene encoding dystrophin protein. About 70% of DMD-causing mutations are exon deletion leading to frameshift of open reading frame and dystrophin deficiency. To facilitate translating human DMD-targeting CRISPR therapeutics into patients, we herein establish a genetically humanized mouse model of DMD by replacing exon 50 and 51 of mouse Dmd gene with human exon 50 sequence. This humanized mouse model recapitulats patient's DMD phenotypes of dystrophin deficiency and muscle dysfunction. Furthermore, we target splicing sites in human exon 50 with adenine base editor to induce exon skipping and robustly restored dystrophin expression in heart, tibialis anterior and diaphragm muscles. Importantly, systemic delivery of base editor via adeno-associated virus in the humanized male mouse model improves the muscle function of DMD mice to the similar level of wildtype ones, indicating the therapeutic efficacy of base editing strategy in treating most of DMD types with exon deletion or point mutations via exon-skipping induction.

Gut microbiota metabolite tyramine ameliorates high-fat diet-induced insulin resistance via increased Ca2+ signaling.

The gut microbiota and their metabolites are closely linked to obesity-related diseases, such as type 2 diabetes, but their causal relationship and underlying mechanisms remain largely elusive. Here, we found that dysbiosis-induced tyramine (TA) suppresses high-fat diet (HFD)-mediated insulin resistance in both Drosophila and mice. In Drosophila, HFD increases cytosolic Ca2+ signaling in enterocytes, which, in turn, suppresses intestinal lipid levels. 16 S rRNA sequencing and metabolomics revealed that HFD leads to increased prevalence of tyrosine decarboxylase (Tdc)-expressing bacteria and resulting tyramine production. Tyramine acts on the tyramine receptor, TyrR1, to promote cytosolic Ca2+ signaling and activation of the CRTC-CREB complex to transcriptionally suppress dietary lipid digestion and lipogenesis in enterocytes, while promoting mitochondrial biogenesis. Furthermore, the tyramine-induced cytosolic Ca2+ signaling is sufficient to suppress HFD-induced obesity and insulin resistance in Drosophila. In mice, tyramine intake also improves glucose tolerance and insulin sensitivity under HFD. These results indicate that dysbiosis-induced tyramine suppresses insulin resistance in both flies and mice under HFD, suggesting a potential therapeutic strategy for related metabolic disorders, such as diabetes.

Guizhitongluo Tablet inhibits atherosclerosis and foam cell formation through regulating Piezo1/NLRP3 mediated macrophage pyroptosis.

BACKGROUND: Atherosclerosis (AS) is the main pathological basis for the development of cardiovascular diseases. Vascular inflammation is an important factor in the formation of AS, and macrophage pyroptosis plays a key role in AS due to its unique inflammatory response. Guizhitongluo Tablet (GZTLT) has shown clinically effective in treating patients with AS, but its mechanism is elusive. PURPOSE: This study was to determine the effects of GZTLT on atherosclerotic vascular inflammation and pyroptosis and to understand its underlying mechanism. MATERIALS AND METHODS: The active constituents of GZTLT were analysed by means of UPLC-HRMS. In vivo experiments were performed using ApoE-/- mice fed a high fat diet for 8 weeks, followed by treatment with varying concentrations of GZTLT orally by gavage and GsMTx4 (GS) intraperitoneally and followed for another 8 weeks. Oil red O, Haematoxylin-eosin (HE) and Masson staining were employed to examine the lipid content, plaque size, and collagen fibre content of the mouse aorta. Immunofluorescence staining was utilised to identify macrophage infiltration, as well as the expression of Piezo1 and NLRP3 proteins in aortic plaques. The levels of aortic inflammatory factors were determined using RT-PCR and ELISA. In vitro, foam cell formation in bone marrow-derived macrophages (BMDMs) was observed using Oil Red O staining. Intracellular Ca2+ measurements were performed to detect the calcium influx in BMDMs, and the expression of NLRP3 and its related proteins were detected by Western blot. RESULTS: The UPLC-HRMS analysis revealed 31 major components of GZTLT. Our data showed that GZTLT inhibited aortic plaque formation in mice and increased plaque collagen fibre content to stabilise plaques. In addition, GZTLT could restrain the expression of serum lipid levels and suppress macrophage foam cell formation. Further studies found that GZTLT inhibited macrophage infiltration in aortic plaques and suppressed the expression of inflammatory factors. It is noteworthy that GZTLT can restrain Piezo1 expression and reduce Ca2+ influx in BMDMs. Additionally, we found that GZTLT could regulate NLRP3 activation and pyroptosis by inhibiting Piezo1. CONCLUSION: The present study suggests that GZTLT inhibits vascular inflammation and macrophage pyroptosis through the Piezo1/NLRP3 signaling pathway, thereby delaying AS development. Our finding provides a potential target for AS treatment and drug discovery.

Observation of conflict triggers conflict adaptation.

The conflict monitoring theory posits that the simultaneous activation of incompatible responses in the current trial leads to response conflict. Conflict occurrence signals to enhance attention to the target stimulus, reduce attention to distracting stimuli, and ultimately lead to conflict adaptation (i.e., reduced interference effect after conflict trials compared to nonconflict trials). However, this theory does not explicitly assume whether the involvement of response execution is necessary in the process of conflict occurrence. Research on the negative emotion theory suggests that even in the absence of response execution, incompatible response representations can induce conflict. Our present study aimed to provide direct behavioural evidence regarding whether conflict activated without response execution is sufficient to trigger conflict adaptation. In a word-colour Stroop task, this study employed the LOOK-to-DO transition design, in which participants refrained from responding in half of the trials (LOOK trials) and responded with key presses in the other half (DO trials). Across three experiments, we controlled for feature integration and contingency learning and manipulated the stimulus presentation duration in the previous trial. The results indicated a significant conflict adaptation effect in reaction time when the stimulus presentation duration was shorter in the previous trial. This finding suggested that in a confounding-minimal design with no response execution in the previous trial, conflict triggers control adjustments and leads to conflict adaptation. This finding aligns with and further elaborates on the original conflict monitoring theory by demonstrating that response execution is not a necessary condition for the generation of response conflict. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Attenuated conflict self-referential information facilitating conflict resolution.

Self-referential information can reduce the congruency effect by acting as a signal to enhance cognitive control. However, it cannot be denied that self-referential information can attract and hold attention. To investigate this issue, the study used a revised Stroop task and recorded behavioral and electrophysiological data from thirty-three participants. We combined event-related potential (ERP) and multivariate pattern analysis (MVPA) to examine the neural correlates of self-referential processing and conflict processing. In the behavioral results, self-referential information reduced the congruency effect. Specifically, self-reference stimuli elicited smaller N2 amplitude than non-self-reference stimuli, indicating that self-referential information was promptly identified and reduced top-down cognitive resource consumption. Self-referential information could be reliably decoded from ERP signals in the early-to-mid stage. Moreover, self-reference conditions exhibited earlier congruency decoding than non-self-reference conditions, facilitating conflict monitoring. In the late stage, under the incongruent condition, self-reference stimuli elicited smaller sustained potential amplitude than non-self-reference stimuli, indicating that cognitive control in the self-reference condition required fewer cognitive resources for conflict resolution. Together, these findings revealed that self-referential information was identified and facilitated conflict monitoring, leading to more effective conflict resolution.

[Development and validation of a nomogram for predicting 3-month mortality risk in patients with sepsis-associated acute kidney injury].

OBJECTIVE: To develop and evaluate a nomogram prediction model for the 3-month mortality risk of patients with sepsis-associated acute kidney injury (S-AKI). METHODS: Based on the American Medical Information Mart for Intensive Care- IV (MIMIC- IV), clinical data of S-AKI patients from 2008 to 2021 were collected. Initially, 58 relevant predictive factors were included, with all-cause mortality within 3 months as the outcome event. The data were divided into training and testing sets at a 7 : 3 ratio. In the training set, univariate Logistic regression analysis was used for preliminary variable screening. Multicollinearity analysis, Lasso regression, and random forest algorithm were employed for variable selection, combined with the clinical application value of variables, to establish a multivariable Logistic regression model, visualized using a nomogram. In the testing set, the predictive value of the model was evaluated through internal validation. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the curve (AUC) was calculated to evaluate the discrimination of nomogram model and Oxford acute severity of illness score (OASIS), sequential organ failure assessment (SOFA), and systemic inflammatory response syndrome score (SIRS). The calibration curve was used to evaluate the calibration, and decision curve analysis (DCA) was performed to assess the net benefit at different probability thresholds. RESULTS: Based on the survival status at 3 months after diagnosis, patients were divided into 7 768 (68.54%) survivors and 3 566 (31.46%) death. In the training set, after multiple screenings, 7 variables were finally included in the nomogram model: Logistic organ dysfunction system (LODS), Charlson comorbidity index, urine output, international normalized ratio (INR), respiratory support mode, blood urea nitrogen, and age. Internal validation in the testing set showed that the AUC of nomogram model was 0.81 [95% confidence interval (95%CI) was 0.80-0.82], higher than the OASIS score's 0.70 (95%CI was 0.69-0.71) and significantly higher than the SOFA score's 0.57 (95%CI was 0.56-0.58) and SIRS score's 0.56 (95%CI was 0.55-0.57), indicating good discrimination. The calibration curve demonstrated that the nomogram model's calibration was better than the OASIS, SOFA, and SIRS scores. The DCA curve suggested that the nomogram model's clinical net benefit was better than the OASIS, SOFA, and SIRS scores at different probability thresholds. CONCLUSIONS: A nomogram prediction model for the 3-month mortality risk of S-AKI patients, based on clinical big data from MIMIC- IV and including seven variables, demonstrates good discriminative ability and calibration, providing an effective new tool for assessing the prognosis of S-AKI patients.

Three-dimensional morphological characterization of blood droplets during the dynamic coagulation process.

In this study, we employed a method integrating optical coherence tomography (OCT) with the U-Net and Visual Geometry Group (VGG)-Net frameworks within a convolutional neural network for quantitative characterization of the three dimensional whole blood during the dynamic coagulation process. VGG-Net architecture for the identification of blood droplets across three distinct coagulation stages including drop, gelation, and coagulation achieves an accuracy of up to 99%. In addition, the U-Net architecture demonstrated proficiency in effectively segmenting uncoagulated and coagulated portions of whole blood, as well as the background. Notably, parameters such as volume of uncoagulated and coagulated segments of the whole blood were successfully employed for the precise quantification of the coagulation process, which indicates well for the potential of future clinical diagnostics and analyses.

Potential therapies for HCC involving targeting the ferroptosis pathway.

Liver cancer ranks as the third leading cause of cancer-related mortality worldwide, predominantly in the form of hepatocellular carcinoma (HCC). Conventional detection and treatment approaches have proven inadequate for addressing the elevated incidence and mortality rates associated with HCC. However, a significant body of research suggests that combating HCC through the induction of ferroptosis is possible. Ferroptosis is a regulated cell death process characterized by elevated levels of reactive oxygen species (ROS) and lipid peroxide accumulation, both of which are dependent on iron levels. In recent years, there has been an increasing focus on investigating ferroptosis, revealing its potential as an inhibitory mechanism against various diseases, including tumors. Therefore, ferroptosis induction holds great promise for treating multiple types of cancers, including HCC. This article provides a review of the key mechanisms involved in ferroptosis and explores the potential application of multiple targets and pathways associated with ferroptosis in HCC treatment to improve therapeutic outcomes.

Identification of cysteine-rich receptor-like kinase gene family in potato: revealed StCRLK9 in response to heat, salt and drought stresses.

The investigation into cysteine-rich receptor-like kinases (CRLKs) holds pivotal significance as these conserved, upstream signalling molecules intricately regulate fundamental biological processes such as plant growth, development and stress adaptation. This study undertakes a comprehensive characterisation of CRLKs in Solanum tuberosum (potato), a staple food crop of immense economic importance. Employing comparative genomics and evolutionary analyses, we identified 10 distinct CRLK genes in potato. Further categorisation into three major groups based on sequence similarity was performed. Each CRLK member in potato was systematically named according to its chromosomal position. Multiple sequence alignment and phylogenetic analyses unveiled conserved gene structures and motifs within the same groups. The genomic distribution of CRLKs was observed across Chromosomes 2-5, 8 and 12. Gene duplication analysis highlighted a noteworthy trend, with most gene pairs exhibiting a Ka/Ks ratio greater than one, indicating positive selection of StCRLKs in potato. Salt and drought stresses significantly impacted peroxidase and catalase activities in potato seedlings. The presence of diverse cis -regulatory elements, including hormone-responsive elements, underscored their involvement in myriad biotic and abiotic stress responses. Interestingly, interactions between the phytohormone auxin and CRLK proteins unveiled a potential auxin-mediated regulatory mechanism. A holistic approach combining transcriptomics and quantitative PCR validation identified StCRLK9 as a potential candidate involved in plant response to heat, salt and drought stresses. This study lays a robust foundation for future research on the functional roles of the CRLK gene family in potatoes, offering valuable insights into their diverse regulatory mechanisms and potential applications in stress management.

Analysis of related factors for pathological upgrading of cervical biopsy from CIN3 to cancer after conical resection.

BACKGROUND: To investigate related factors for postoperative pathological upgrading of cervical biopsy to cervical cancer (CC) in patients with cervical intraepithelial neoplasia (CIN)3 after conical resection. METHODS: This retrospective study collected data from patients diagnosed with CIN3 by cervical biopsies at the author's Hospital between January 2012 and December 2022. The primary outcome was the pathological results of patients after conical resection. The pathological findings were categorized into the pathological upgrading group if postoperative pathology indicated CC, while those with normal, inflammatory, or cervical precancerous lesions were classified into the pathological non-upgrading group. The factors associated with upgrading were identified using multivariable logistic regression analysis. RESULTS: Among 511 patients, there were 125 patients in the pathological upgrading group (24.46%). The patients in the upgrading group were younger (47.68 ± 9.46 vs. 52.11 ± 7.02, P < 0.001), showed a lower proportion of menopausal women (38.40% vs. 53.02%, P = 0.0111), a lower proportion of HSIL (40.00% vs. 57.77%, P = 0.001), a higher rate of HPV-16/18 positive (25.60% vs. 17.36%, P = 0.011), a higher rate of contact bleeding (54.40% vs. 21.50%, P < 0.001), lower HDL levels (1.31 ± 0.29 vs. 1.37 ± 0.34 mmol/L, P = 0.002), higher neutrophil counts (median, 3.50 vs. 3.10 × 109/L, P = 0.001), higher red blood cell counts (4.01 ± 0.43 vs. 3.97 ± 0.47 × 1012/L, P = 0.002), higher platelet counts (204.84 ± 61.24 vs. 187.06 ± 73.66 × 109/L, P = 0.012), and a smaller platelet volume (median, 11.50 vs. 11.90 fL, P = 0.002).The multivariable logistic regression analysis showed that age (OR = 0.90, 95% CI: 0.86-0.94, P < 0.001), menopausal (OR = 2.68, 95% CI: 1.38-5.22, P = 0.004), contact bleeding (OR = 4.80, 95% CI: 2.91-7.91, P < 0.001), and mean platelet volume (OR = 0.83, 95% CI: 0.69-0.99, P = 0.038) were independently associated with pathological upgrading from CIN3 to CC after conical resection. CONCLUSION: Age, menopausal, contact bleeding, and mean platelet volume are risk factors of pathological upgrading from CIN3 to CC after conical resection, which could help identify high risk and susceptible patients of pathological upgrading to CC.

Correction of human nonsense mutation via adenine base editing for Duchenne muscular dystrophy treatment in mouse.

Duchenne muscular dystrophy (DMD) is the most prevalent herediatry disease in men, characterized by dystrophin deficiency, progressive muscle wasting, cardiac insufficiency, and premature mortality, with no effective therapeutic options. Here, we investigated whether adenine base editing can correct pathological nonsense point mutations leading to premature stop codons in the dystrophin gene. We identified 27 causative nonsense mutations in our DMD patient cohort. Treatment with adenine base editor (ABE) could restore dystrophin expression by direct A-to-G editing of pathological nonsense mutations in cardiomyocytes generated from DMD patient-derived induced pluripotent stem cells. We also generated two humanized mouse models of DMD expressing mutation-bearing exons 23 or 30 of human dystrophin gene. Intramuscular administration of ABE, driven by ubiquitous or muscle-specific promoters could correct these nonsense mutations in vivo, albeit with higher efficiency in exon 30, restoring dystrophin expression in skeletal fibers of humanized DMD mice. Moreover, a single systemic delivery of ABE with human single guide RNA (sgRNA) could induce body-wide dystrophin expression and improve muscle function in rotarod tests of humanized DMD mice. These findings demonstrate that ABE with human sgRNAs can confer therapeutic alleviation of DMD in mice, providing a basis for development of adenine base editing therapies in monogenic diseases.

Construction of a high-density genetic map based on large-scale marker development in Coix lacryma-jobi L. using specific-locus amplified fragment sequencing (slaf-seq).

Coix lacryma-jobi L. is one of the most economically and medicinally important corns. This study constructed a high-density genetic linkage map of C. lacryma-jobi based on a cross between the parents 'Qianyi No. 2' × 'Wenyi No. 2' and their F2 progeny through high-throughput sequencing and the construction of a specific-locus amplified fragment (SLAF) library. After pre-processing, 325.49 GB of raw data containing 1628 M reads were obtained. A total of 22,944 high-quality SLAFs were identified, among which 3952 SLAFs and 3646 polymorphic markers met the requirements for the construction of a genetic linkage map. The integrated map contained 3605 high-quality SLAFs, which were grouped into ten genetic linkage groups. The total length of the map was 1620.39 cM, with an average distance of 0.45 cM and an average of 360.5 markers per linkage group. This report presents the first high-density genetic map of C. lacryma-jobi. This map was constructed using an F2 population and SLAF-seq approach, which allows the development of a large number of polymorphic markers in a short period. These results provide a platform for precise gene/quantitative trait locus (QTL) mapping, map-based gene separation, and molecular breeding in C. lacryma-jobi. They also help identify a target gene for tracking, splitting quantitative traits, and estimating the phenotypic effects of each QTL for QTL mapping. They are of great significance for improving the efficiency of discovering and utilizing excellent gene resources of C. lacryma-jobi.

Pressure-Insensitive Epidermal Thickness of Fingertip Skin for Optical Image Encryption.

In this study, an internal fingerprint-guided epidermal thickness of fingertip skin is proposed for optical image encryption based on optical coherence tomography (OCT) combined with U-Net architecture of a convolutional neural network (CNN). The epidermal thickness of fingertip skin is calculated by the distance between the upper and lower boundaries of the epidermal layer in cross-sectional optical coherence tomography (OCT) images, which is segmented using CNN, and the internal fingerprint at the epidermis-dermis junction (DEJ) is extracted based on the maximum intensity projection (MIP) algorithm. The experimental results indicate that the internal fingerprint-guided epidermal thickness is insensitive to pressure due to normal correlation coefficients and the encryption process between epidermal thickness maps of fingertip skin under different pressures. In addition, the result of the numerical simulation demonstrates the feasibility and security of the encryption scheme by structural similarity index matrix (SSIM) analysis between the original image and the recovered image with the correct and error keys decryption, respectively. The robustness is analyzed based on the SSIM value in three aspects: different pressures, noise attacks, and data loss. Key randomness is valid by the gray histograms, and the average correlation coefficients of adjacent pixelated values in three directions and the average entropy were calculated. This study suggests that the epidermal thickness of fingertip skin could be seen as important biometric information for information encryption.

Impact of high-performance human papillomavirus testing to improve cervical cancer screening in China: a prospective population-based multicentre cohort study.

OBJECTIVES: The aim of the study was to evaluate the clinical performance of HBRT-H14, a real-time PCR-based assay that separates human papillomavirus (HPV) 16 and HPV18 from 12 other high-risk (HR) HPV types, in population according to Chinese guideline. METHODS: A total of 9829 eligible women aged 21-64 years from Henan, Shanxi, and Guangdong provinces were performed by HBRT-H14 testing and liquid-based cytology (LBC) screening at baseline and followed up for 3-year. The sensitivity, specificity, positive predictive value (absolute risk), and negative predictive value of LBC diagnosis and HPV testing were calculated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) Lesions. RESULTS: At baseline, 80 (0.81%) participants were diagnosed with CIN2+. HR-HPV with reflex LBC had a significantly higher sensitivity (78/80, 97.50% [95% CI, 91.34-99.31%] vs. 62/80, 77.50% [67.21-85.27%], McNemar's test p < 0.001), and a slightly lower specificity (8528/9749, 87.48% [86.80-88.12%] vs. 8900/9749, 91.29% [90.72-91.83%], McNemar's test p < 0.001) than LBC with reflex HR-HPV for CIN2+. 7832 (79.6%) participants completed 3-year follow-up and 172 (2.20%) participants were cumulatively diagnosed with CIN2+. Compared with LBC with reflex HR-HPV, HR-HPV with reflex LBC significantly increased the sensitivity (161/172, 93.60% [88.91-96.39%] vs. 87/172, 50.58% [43.18-57.96%], McNemar's test p < 0.001), but marginally decreased the specificity (6776/7660, 88.46% [87.72-89.16%] vs. 6933/7660, 90.51% [89.83-91.15], McNemar's test p < 0.001). In addition, the absolute 3-year risk of CIN2+ in HPV16/18-positive individuals was as high as 33% (80/238), whereas the risk in the HPV-negative population was only 0.16% (11/6787), much lower than those in the negative for intraepithelial lesion or malignancy population (1.21%, 85/7018). Moreover, similar results were found in women ≥30 years old. DISCUSSION: The study has indicated that HBRT-14 has a reliable clinical performance for use in cervical screening. The validated HPV test would improve the quality of population screening.

The neural dynamics of conflict adaptation induced by conflict observation: Evidence from univariate and multivariate analysis.

Conflict adaptation can be expressed as greater performance (shorter response time and lower error rate) after incongruent trials when compared to congruent trials. It has been observed in designs that minimize confounding factors, i.e., feature integration, contingency learning, and temporal learning. Our current study aimed to further elucidate the temporal evolution mechanisms of conflict adaptation. To address this issue, the current study employed a combination of behavioral, univariate, and multivariate analysis (MVPA) methods in a modified color-word Stroop task, where half of the trials required button presses (DO trials), and the other half only required observation (LOOK trials). Both behavioral and the ERP results (N450 and SP) in the LOOK-DO transition trials revealed significant conflict adaptation without feature integration, contingency learning, and temporal learning, providing support for the conflict monitoring theory. Furthermore, during the LOOK trials, significant Stroop effect in the N450 and SP components were observed, indicating that conflict monitoring occurred at the stimulus level and triggered reactive control adjustments. The MVPA results decoded the congruent-incongruent and incongruent-incongruent conditions during the conflict adjustment phase but not during the conflict monitoring phase, emphasizing the unique contribution of conflict adjustment to conflict adaptation. The current research findings provided more compelling supporting evidence for the conflict monitoring theory, while also indicating that future studies should employ the present design to elucidate the specific processes of conflict adaptation.

Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling.

The dynamic remodeling of the cytoskeletal network of vimentin intermediate filaments network supports various cellular functions, including cell morphology, elasticity, migration, organelle localization, and resistance against mechanical or pathological stress. Currently available chemicals targeting vimentin predominantly induce network reorganization and shrinkage around the nucleus. Effective tools for long-term manipulation of vimentin network dispersion in living cells are still lacking, limiting in-depth studies on vimentin function and potential therapeutic applications. Here, we verified that a commercially available small molecule, Trametinib, is capable of inducing spatial spreading of the cellular vimentin network without affecting its transcriptional or translational regulation. Further evidence confirmed its low cytotoxicity and similar effects on different cell types. Importantly, Trametinib has no impact on the other two cytoskeletal systems, actin filaments and the microtubule network. Moreover, Trametinib regulates vimentin network dispersion rapidly and efficiently, with effects persisting for up to 48 h after drug withdrawal. We also ruled out the possibility that Trametinib directly affects the phosphorylation level of vimentin. In summary, we identified an unprecedented regulator, Trametinib, capable of spreading the vimentin network toward the cell periphery, and thus complemented the existing repertoire of vimentin remodeling drugs in the field of cytoskeletal research.

Evaluation of three prediction formulas of 24-hour urinary sodium excretion in Chinese residents: a systematic review and meta-analysis.

OBJECTIVE: To determine the appropriateness of three widely used formulas estimating 24-h urinary Na (24hUNa) from spot urine samples in the Chinese population. DESIGN: Systematic review and meta-analysis. SETTING: Literature review was conducted to identify studies for estimating 24hUNa using the Kawasaki, Tanaka and INTERSALT formulas simultaneously in PubMed, Embase and the Cochrane library databases. The mean difference (MD) and correlation coefficients (r) between measures and estimates from different formulas were assessed. PARTICIPANTS: Information extraction and quality assessment were performed in thirteen studies involving 8369 subjects. RESULTS: Two studies which affected the overall robustness were excluded in the 'leave-one-out' sensitivity analyses. Within the final meta-analysis included eleven studies and 7197 participants, 36·07 mmol/d (95 %CI 16·89, 55·25) of MD was observed in the Kawasaki formula, and -19·62 mmol/d (95 %CI -37·37, -1·87) in the Tanaka formula and -35·78 mmol/d (95 %CI -50·76, -20·80) in the INTERSALT formula; a pooled r-Fisher's Z of 0·39 (95 %CI 0·32, 0·45) in the Kawasaki formula, 0·43 (95 %CI 0·37, 0·49) in the Tanaka formula and 0·36 (95 %CI 0·31, 0·42) in the INTERSALT formula. Subgroup analyses were conducted to explore the possible factors affecting the accuracy of the formula estimation from three mainly aspects: population types, Na intake levels and urine specimen types. CONCLUSIONS: The meta-analysis suggested that the Tanaka formula performed a more accurate estimate in Chinese population. Time of collecting spot urine specimens and Na intake level of the sample population might be the main factors affecting the accuracy of the formula estimation.