HIV Services Uptake Among People Living with HIV in Jiangsu Province, China: A Cross-Sectional Study.

Healthcare disparities are common among people living with HIV (PLWH) in China and likely impact access to HIV services. This study aimed to assess the current status of access to HIV services among PLWH and explore the correlates of service uptake using baseline data from a prospective cohort study among PLWH in Jiangsu Province. Guided by Andersen's behavioral model, univariable and multivariable logistic regressions were conducted to identify factors associated with access to HIV services. Out of 8989 eligible PLWH included in this study, 46.4% perceived difficulty in seeing a healthcare professional for HIV treatment services in 2021-2022. PLWH aged 18-34 years (adjusted odds ratio [AOR] = 1.69, 95% CI 1.32-2.15), 35-39 years (AOR = 1.33, 95% CI 1.08-1.65), identified as a bisexual/other (AOR = 1.14, 95% CI 1.01-1.29), had a college and above education (AOR = 1.32, 95% CI 1.07-1.63), and perceived moderate (AOR = 1.70, 95% CI 1.51-1.91) and severe (AOR = 2.20, 95% CI 1.94-2.49) levels of HIV stigma were more likely to perceive difficulty in seeing healthcare professionals for HIV treatment in 2021-2022. Living in northern Jiangsu was also associated with increased odds of perceiving difficulty in seeing healthcare professionals for HIV treatment (AOR = 1.12, 95% CI 1.00-1.26). These findings underscore the need for innovative solutions to eliminate the practical barriers to HIV services utilization among PLWH who are bisexual, well-educated, and effective HIV-related stigma reduction interventions.

Construction and validation of the nomogram predictive model for post-percutaneous nephrolithotomy urinary sepsis.

OBJECTIVE: This study aimed to construct and validate a simple and accurate clinical nomogram for predicting the occurrence of post-percutaneous nephrolithotomy sepsis, aiming to assist urologists in the early identification, warning, and early intervention of urosepsis, and to provide certain evidence-based medicine basis. METHODS: This study included patients who underwent PCNL surgery due to kidney or upper ureteral stones at the Department of Urology, Affiliated Hospital of Zunyi Medical University, from January 2019 to September 2022. This study utilized univariate and multivariate logistic regression analysis to screen and evaluate the risk factors for sepsis and construct a predictive model. An evaluation was performed using the receiver operating characteristic curve, calibration curve, and decision curve analysis curve. All statistical analyses were conducted using R version 4.2. RESULTS: A total of 946 patients who underwent post-PCNL were included in this study, among whom 69 patients (7.29%) developed post-PCNL urinary sepsis. Multiple-factor logistic regression analysis identified four independent risk factors associated with post-PCNL urinary sepsis, including positive urinary nitrite (OR = 5.9, P < 0.001), positive urine culture (OR = 7.54, P < 0.001), operative time ≥ 120 min (OR = 20.93, P = 0.0052), and stone size ≥ 30 mm (OR = 13.81, P = 0.0015). The nomogram model demonstrated good accuracy with an AUC value of 0.909, and in the validation cohort, the AUC value was 0.922. The calibration curve indicated a better consistency between the predictive line chart and the actual occurrence of post-PCNL urinary sepsis. The decision curve analysis curve showed favorable clinical utility. CONCLUSION: Preoperative positive urine culture, positive urinary nitrite, operative time ≥ 120 min, and stone size ≥ 30 mm are independent risk factors for developing post-PCNL urinary sepsis. The constructed line chart based on these factors effectively assesses the risk of urinary sepsis in patients after PCNL.

The Development and Evaluation of a Prediction Model for Kidney Transplant-Based Pneumocystis carinii Pneumonia Patients Based on Hematological Indicators.

BACKGROUND: This study aimed to develop a simple predictive model for early identification of the risk of adverse outcomes in kidney transplant-associated Pneumocystis carinii pneumonia (PCP) patients. METHODS: This study encompassed 103 patients diagnosed with PCP, who received treatment at our hospital between 2018 and 2023. Among these participants, 20 were categorized as suffering from severe PCP, and, regrettably, 13 among them succumbed. Through the application of machine learning techniques and multivariate logistic regression analysis, two pivotal variables were discerned and subsequently integrated into a nomogram. The efficacy of the model was assessed via receiver operating characteristic (ROC) curves and calibration curves. Additionally, decision curve analysis (DCA) and a clinical impact curve (CIC) were employed to evaluate the clinical utility of the model. The Kaplan-Meier (KM) survival curves were utilized to ascertain the model's aptitude for risk stratification. RESULTS: Hematological markers, namely Procalcitonin (PCT) and C-reactive protein (CRP)-to-albumin ratio (CAR), were identified through machine learning and multivariate logistic regression. These variables were subsequently utilized to formulate a predictive model, presented in the form of a nomogram. The ROC curve exhibited commendable predictive accuracy in both internal validation (AUC = 0.861) and external validation (AUC = 0.896). Within a specific threshold probability range, both DCA and CIC demonstrated notable performance. Moreover, the KM survival curve further substantiated the nomogram's efficacy in risk stratification. CONCLUSIONS: Based on hematological parameters, especially CAR and PCT, a simple nomogram was established to stratify prognostic risk in patients with renal transplant-related PCP.

A Mixture Fluency model using responses and response times with cognitive diagnosis model framework.

Random guessing behaviors are frequently observed in low-stakes assessments, often attributed to factors such as test-takers lacking motivation or experiencing time constraints and fatigue. Existing research suggests that responses stemming from random guessing behaviors introduce biases into the constructs and relationships of interest. This is particularly problematic when estimating the relationship between speed and ability. This study introduces a Mixture Fluency model designed to account for random guessing behaviors while utilizing valid response accuracy and response time to uncover students' latent attribute profiles. The model directly addresses a limitation present in the Fluency cognitive diagnostic model (Wang & Chen, Psychometrika, 85, 600-629, (2020), which assumes that test-takers consistently employ solution behaviors when answering questions. To investigate the effectiveness of the proposed Mixture Fluency model, we conducted a simulation study encompassing various simulation conditions. Results from this study not only confirm the model's ability to detect potential random guessing behaviors but also demonstrate its capacity to enhance the inference of targeted latent constructs within the assessment. Additionally, we showcase the practical utility of the proposed model through an application to real data.

Modulation of macrophage polarity with carboxymethyl chitin gated hollow mesoporous silica nanoparticles for elevating anti-tumor chemotherapy.

The weak immunity of tumors after chemotherapy could cause tumor metastasis and progression. Therefore, to overcome the dilemma of obvious immune deficiency caused by chemotherapy, a nanosystem (N-IL-12/DOX/α-TOS) consisted of thioketal (TK) bonds linked-hollow mesoporous silica nanoparticles (HMSNs) coated with carboxymethyl chitin (CMCH) by electrostatic interaction, and surface-functionalized glucose-regulated protein 78 binding peptide was prepared for loading doxorubicin (DOX), IL-12 and α-tocopheryl succinate (α-TOS). N-IL-12/DOX/α-TOS displayed a mean size of 275 nm after encapsulated DOX, IL-12 and α-TOS with loading contents of 2.04 × 10-4, 4.01 × 10-2 and 7.12 × 10-2, respectively. The drug-free nanoparticles (NPs) showed good biocompatibility to both 4 T1 cells and RAW264.7 macrophages. N-IL-12/DOX/α-TOS could achieve localized release of IL-12, DOX and α-TOS by pH and H2O2 trigger in the tumor microenvironment (TME). Moreover, the combined therapy by N-IL-12/DOX/α-TOS remarkably elevated the anti-tumor therapeutic efficacy, enhanced immune responses via promoting tumor-associated macrophage (TAM) polarization into tumoricidal M1 phenotypes, and decreased lung metastasis with reduced side effects. N-IL-12/DOX/α-TOS exhibited as a promising strategy for combining chemotherapy and local macrophage modulation-immunotherapy for anti-tumor therapy.

Validation of the kidney donor profile index (KDPI) for deceased donor kidney transplants in China.

BACKGROUND: The kidney donor profile index (KDPI) evaluates kidney donor's age, height, weight, ethnicity, cause of death, high blood pressure, diabetes, exposure to hepatitis C and estimated glomerular filtration (eGFR). Kidneys with lower KDPI scores are expected to function longer that those with higher KPDI values. The applicability of KDPI score in Chinese kidney transplant donation has not yet been validated. This study evaluated the prognostic value of KDPI score in Chinese kidney transplant patients. METHODS: A retrospective analysis was conducted on 184 deceased donors and 353 corresponding kidney transplant patients at the Organ Transplantation Department of Renmin Hospital of Wuhan University between 2018 and 2021. The donors and recipients were stratified into four groups based on their KDPI score: KDPI 85-100, KDPI 60-84, KDPI 21-59, and KDPI 0-20. RESULTS: As expected, the KDPI 85-100 group was associated with a poor short-term renal function (both postoperative creatinine and eGFR with P > 0.05), a higher incidence of delayed graft function (DGF; 25.5% for KDPI 85-100 group vs. 10.2% for KDPI 60-84 group vs. 5.4% for KDPI 21-59 group vs. 0 for KDPI 0-20 group, all P > 0.05). Furthermore, the same groups showed worse 3-year patient survival rate: 86.3% for KDPI 85-100 group vs. 97.01% for KDPI 60-84 group vs. 97.83% for KDPI 21-59 group vs. 100% for KDPI 0-20 group, all P > 0.05); and renal survival rate: 82.6% for KDPI 85-100 group vs. 92.99% KDPI 60-84 group vs.97.83% for KDPI 21-59 group vs. 100% for KDPI 0-20 group, all P > 0.05). Our analysis showed that the KDPI score had a good predictive value for the survival of kidney transplants and patients in our center (area under the curve: 0.728 and 0.76, P > 0.05). CONCLUSION: We recommend that the KDPI scoring system can be employed as an effective tool to predict kidney transplantation outcomes in deceased donation in China.

A new experimental rat model of nocebo-related nausea involving double mechanisms of observational learning and conditioning.

AIM: The nocebo effect, such as nausea and vomiting, is one of the major reasons patients discontinue therapy. The underlying mechanisms remain unknown due to a lack of reliable experimental models. The goal of this study was to develop a new animal model of nocebo-related nausea by combining observational learning and Pavlovian conditioning paradigms. METHODS: Male Sprague-Dawley rats with nitroglycerin-induced migraine were given 0.9% saline (a placebo) or LiCl (a nausea inducer) following headache relief, according to different paradigms. RESULTS: Both strategies provoked nocebo nausea responses, with the conditioning paradigm having a greater induction impact. The superposition of two mechanisms led to a further increase in nausea responses. A preliminary investigation of the underlying mechanism revealed clearly raised peripheral and central cholecystokinin (CCK) levels, as well as specific changes in the 5-hydroxytryptamine and cannabinoid systems. Brain networks related to emotion, cognition, and visceral sense expressed higher c-Fos-positive neurons, including the anterior cingulate cortex (ACC), insula, basolateral amygdala (BLA), thalamic paraventricular nucleus (PVT), hypothalamic paraventricular nucleus (PVN), nucleus tractus solitarius (NTS), periaqueductal gray (PAG), and dorsal raphe nucleus-dorsal part (DRD). We also found that nausea expectances in the model could last for at least 12 days. CONCLUSION: The present study provides a useful experimental model of nocebo nausea that might be used to develop potential molecular pathways and therapeutic strategies for nocebo.

Sentrin-specific protease 1 maintains mitochondrial homeostasis through targeting the deSUMOylation of sirtuin-3 to alleviate oxidative damage induced by hepatic ischemia/reperfusion.

Hepatic ischemia/reperfusion injury (HIRI) represents a prevalent pathophysiological process that imposes a substantial economic burden in clinical practice, especially in liver surgery. Sentrin-specific protease 1 (SENP1) is a crucial enzyme involved in the regulation of SUMOylation, and is related to various diseases. However, the role of SENP1 in HIRI remains unexplored. Here, we confirmed that SENP1 actively participated in modulating the oxidative damage induced by HIRI. Notably, SENP1 functioned by maintaining mitochondrial homeostasis. Further mechanistic exploration indicated that the protective mitochondrial protein sirtuin-3 (Sirt3) was inactivated by SUMOylation during HIRI, which was reversed by SENP1. Overexpression of SENP1 could restore mitochondrial function, mitigate oxidative stress and attenuated apoptosis through recovering the expression of Sirt3 during HIRI. Nevertheless, 3-TYP, an inhibitor of Sirt3, could eliminate the therapeutic effects brought by overexpression of SENP1. In conclusion, our findings demonstrated that SENP1 mediated the deSUMOylation of Sirt3 and maintained mitochondrial homeostasis, thus alleviating HIRI induced oxidative damage. SENP1 might be a promising therapeutic target for HIRI.

Hepatocellular SETDB1 Regulates Hepatic Ischemia-Reperfusion Injury through Targeting Lysine Methylation of ASK1 Signal.

Background: Hepatic ischemia-reperfusion injury (HIRI) stands as an unavoidable complication arising from liver surgery, profoundly intertwined with its prognosis. The role of lysine methyltransferase SET domain bifurcated 1 (SETDB1) in HIRI remains elusive, despite its confirmation as a potential therapeutic target for diverse diseases. Here, we investigated the mechanism by which SETDB1 regulated HIRI. Methods: RNA sequencing data were used to identify the expression and potential targets of SETDB1 through bioinformatics analysis. To elucidate the impact of SETDB1 on HIRI, both an in vivo model of HIRI in mice and an in vitro model of hepatocyte hypoxia/reoxygenation were established. Biochemical and histological analyses were used to investigate the influence of SETDB1 on liver damage mediated by HIRI. Chromatin immunoprecipitation and coimmunoprecipitation were implemented to explore the in-depth mechanism of SETDB1 regulating HIRI. Results: We confirmed that hepatocellular SETDB1 was up-regulated during HIRI and had a close correlation with HIRI-related inflammation and apoptosis. Moreover, inhibition of SETDB1 could mitigate HIRI-induced liver damage, inflammation, and apoptosis. Through our comprehensive mechanistic investigation, we revealed that SETDB1 interacts with apoptosis-signal-regulating kinase 1 (ASK1) and facilitates the methylation of its lysine residues. Inhibition of SETDB1 resulted in reduced phosphorylation of ASK1, leading to a marked suppression of downstream c-Jun N-terminal kinase (JNK)/p38 signaling pathway activation. The therapeutic effect on inflammation and apoptosis achieved through SETDB1 inhibition was nullified by the restoration of JNK/p38 signaling activation through ASK1 overexpression. Conclusions: The findings from our study indicate that SETDB1 mediates lysine methylation of ASK1 and modulates the activation of the ASK1-JNK/p38 pathway, thus involved in HIRI-induced inflammation and apoptosis. These results suggest that SETDB1 holds promise as a potential therapeutic target for mitigating HIRI.

Inhibition of SK Channels in VTA Affects Dopaminergic Neurons to Improve the Depression-Like Behaviors of Post-Stroke Depression Rats.

Purpose: This study aimed to investigate the effect of small-conductance calcium-activated potassium channels (SK channels) on the dopaminergic (DA) neuron pathways in the ventral tegmental area (VTA) during the pathogenesis of post-stroke depression (PSD) and explore the improvement of PSD by inhibiting the SK channels. Patients and Methods: Four groups of Sprague-Dawley rats were randomly divided: Control, PSD, SK channel inhibitor (apamin) and SK channel activator (CyPPA) groups. In both control and CyPPA groups, sham surgery was performed. In the other two groups, middle cerebral arteries were occluded. The behavioral indicators related to depression in different groups were compared. Immunofluorescence was used to measure the activity of DA neurons in the VTA, while qRT-PCR was used to assess the expression of SK channel genes. Results: The results showed that apamin treatment improved behavioral indicators related to depression compared to the PSD group. Furthermore, the qRT-PCR analysis revealed differential expression of the KCNN1 and KCNN3 subgenes of the SK channels in each group. Immunofluorescence analysis revealed an increase in the expression of DA neurons in the VTA of the PSD group, which was subsequently reduced upon apamin intervention. Conclusion: This study suggests that SK channel activation following stroke contributes to depression-related behaviors in PSD rats through increased expression of DA neurons in the VTA. And depression-related behavior is improved in PSD rats by inhibiting the SK channels. The results of this study provide a new understanding of PSD pathogenesis and the possibility of developing new strategies to prevent PSD by targeting SK channels.

Prevention and Control Are Not a Regional Matter: A Spatial Correlation and Molecular Linkage Analysis Based on Newly Reported HIV/AIDS Patients in 2021 in Jiangsu, China.

HIV-related spatial analysis studies in China are relatively few, and Jiangsu Province has not reported the relevant data in recent years. To describe the spatial distribution and molecular linkage characteristics of HIV-infected patients, this article combined descriptive epidemiology, spatial analysis, and molecular epidemiology methods to analyze patient reporting, patient mobility information, and HIV sequence information simultaneously. The results showed that HIV reporting profiles differed among Jiangsu cities, with the reporting rate in southern Jiangsu being above average. There was a spatial autocorrelation (Global Moran I = 0.5426, p < 0.05), with Chang Zhou showing a High-High aggregation pattern. Chang Zhou and Wu Xi were identified as hotspots for HIV reporting and access to molecular transmission networks. Some infected individuals still showed cross-city or even cross-province mobility after diagnosis, and three were linked with individuals in the destination cities within the largest molecular transmission cluster, involving 196 patients. The cross-city or cross-province mobility of patients may result in a potential HIV transmission risk, suggesting that combining timely social network surveys, building an extensive transmission network across cities and provinces, and taking critical regions and key populations as entry points could contribute to improved prevention and control efficiency and promote achievement of the 95-95-95 target and cascade.

HPV Infection Profiles among People Living with HIV and HPV Vaccine Acceptance among Individuals with Different HIV Infection Statuses in China: A Systematic Meta-Analysis.

To understand the HPV infection profiles among Chinese HIV/AIDS patients and the HPV vaccine acceptance among unvaccinated Chinese people with different HIV infection statuses after the HPV vaccine launch in China, this study searched Web of Science, PubMed, Cochrane Library, Embase, Scopus, CNKI, WANFANG, SinoMed, and VIP databases up to 23 June 2023, according to the registered protocol (CRD42023449913). A total of 58 studies were included. The results showed that the HPV infection rate among Chinese HIV/AIDS patients was 52.54% (95% CI: 42.11-62.86%) and higher in males than in females (74.55% vs. 41.04%); meanwhile, the rate was higher in the anus than in the cervix (69.22% vs. 41.71%). Although there was no statistical difference, the high-risk HPV infection rate (38.98%) was higher than low-risk HPV (23.86%), and single infections were more common (28.84%) than multiple infections (19.23%). HPV vaccine acceptance among the unvaccinated Chinese population was 59.19% (95% CI: 52.50-65.89%), and was slightly higher among HIV-infected rather than non-HIV-infected individuals (67.72% vs. 59.58%). There was a difference in acceptance among respondents from different regions. Although the difference in acceptance rate between males and females was not statistically significant (61.10% vs. 61.18%), MSM had a higher acceptance rate than non-MSM (84.28% vs. 59.05%). HPV infection is prevalent among HIV patients, demonstrating the need to increase the frequency of HPV screening for PLWH. The HPV vaccine acceptance rate is higher than that of non-HIV-infected individuals. Male acceptance is almost the same as female's, with MSM acceptance higher than non-MSM, suggesting that using MSM, especially MSM in PLWH, as an entry point may be a practical avenue to explore to further expand the scope of HPV vaccination.

The utilization of nanopore targeted sequencing proves to be advantageous in the identification of infections present in deceased donors.

Background: Nanopore Target Sequencing (NTS) represents a novel iteration of gene sequencing technology; however, its potential utility in the detection of infection in deceased donors has yet to be documented. The present study endeavors to assess the applicability of NTS in this domain. Methods: This retrospective study comprised a cohort of 71 patients who were under intensive care at Renmin Hospital of Wuhan University between June 2020 and January 2022. The specimens were subjected to microbiological tests utilizing NTS, culture, and other techniques, and subsequently, the diagnostic accuracy of NTS was compared with conventional methods. Results: Blood NTS exhibited a better agreement rate of 52.11% and a greater positive rate of pathogen detection than blood culture (50.70% vs. 5.63%, p < 0.001). In NTS of deceased donors, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii were the most frequently found bacteria, and Candida was the most frequently found fungus. Blood NTS had a considerably better sensitivity for detecting clinical bloodstream infection than blood culture (62.50%: 7.14%, p < 0.001). These findings were supported by comparisons between blood NTS and conventional microbial detection methods (such as blood culture, glucan testing, galactomannan testing, T cell spot testing for tuberculosis infection, smear, etc.). Conclusion: The pathogen detection technology NTS has a high sensitivity and positive rate. It can more accurately and earlier detect infection in deceased donors, which could be very important for raising the donation conversion rate.

Machine Learning Models for Prediction of Severe Pneumocystis carinii Pneumonia after Kidney Transplantation: A Single-Center Retrospective Study.

BACKGROUND: The objective of this study was to formulate and validate a prognostic model for postoperative severe Pneumocystis carinii pneumonia (SPCP) in kidney transplant recipients utilizing machine learning algorithms, and to compare the performance of various models. METHODS: Clinical manifestations and laboratory test results upon admission were gathered as variables for 88 patients who experienced PCP following kidney transplantation. The most discriminative variables were identified, and subsequently, Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), K-Nearest Neighbor (KNN), Light Gradient Boosting Machine (LGBM), and eXtreme Gradient Boosting (XGB) models were constructed. Finally, the models' predictive capabilities were assessed through ROC curves, sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and F1-scores. The Shapley additive explanations (SHAP) algorithm was employed to elucidate the contributions of the most effective model's variables. RESULTS: Through lasso regression, five features-hemoglobin (Hb), Procalcitonin (PCT), C-reactive protein (CRP), progressive dyspnea, and Albumin (ALB)-were identified, and six machine learning models were developed using these variables after evaluating their correlation and multicollinearity. In the validation cohort, the RF model demonstrated the highest AUC (0.920 (0.810-1.000), F1-Score (0.8), accuracy (0.885), sensitivity (0.818), PPV (0.667), and NPV (0.913) among the six models, while the XGB and KNN models exhibited the highest specificity (0.909) among the six models. Notably, CRP exerted a significant influence on the models, as revealed by SHAP and feature importance rankings. CONCLUSIONS: Machine learning algorithms offer a viable approach for constructing prognostic models to predict the development of severe disease following PCP in kidney transplant recipients, with potential practical applications.

A comprehensive survival and prognosis analysis of GPR55 expression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common subtype, accounting for about 90% of all primary liver cancers. The liver is rich in a large number of immune cells, thus forming a special immune microenvironment, which plays a key role in the occurrence and development of hepatocellular carcinoma. Nowadays, tumor immunotherapy has become one of the most promising cancer treatment methods. Immune checkpoint inhibitors (ICIs) combined with VEGF inhibitors are listed as first-line treatment options for advanced HCC. Therefore, the search for a potential biomarker to predict the response to immunotherapy in HCC patients is urgently needed. The G protein-coupled receptor 55 (GPR55), a lysophosphatidylinositol (LPI) receptor, has recently emerged as a potential new target for anti-tumor therapy. Previous studies have found that GPR55 is highly expressed in breast cancer, pancreatic cancer, skin cancer and cholangiocarcinoma, and is involved in tumor proliferation and migration. However, the role and mechanism of GPR55 in HCC has not been elucidated. Therefore, this article discusses the clinical significance of GPR55 in HCC and its correlation with the immune response of HCC patients, so as to provide theoretical basis for improving the prognosis of HCC.

CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation.

BACKGROUND: CDC42 is a member of Rho GTPase family, acting as a molecular switch to regulate cytoskeleton organization and junction maturation of epithelium in organ development. Tooth root pattern is a highly complicated and dynamic process that dependens on interaction of epithelium and mesenchyme. However, there is a lack of understanding of the role of CDC42 during tooth root elongation. METHODS: The dynamic expression of CDC42 was traced during tooth development through immunofluorescence staining. Then we constructed a model of lentivirus or inhibitor mediated Cdc42 knockdown in Herwig's epithelial root sheath (HERS) cells and dental papilla cells (DPCs), respectively. Long-term influence of CDC42 abnormality was assessed via renal capsule transplantation and in situ injection of alveolar socket. RESULTS: CDC42 displayed a dynamic spatiotemporal pattern, with abundant expression in HERS cells and apical DPCs in developing root. Lentivirus-mediated Cdc42 knockdown in HERS cells didn't disrupt cell junctions as well as epithelium-mesenchyme transition. However, inhibition of CDC42 in DPCs undermined cell proliferation, migration and odontogenic differentiation. Wnt/ß-catenin signaling as the downstream target of CDC42 modulated DPCs' odontogenic differentiation. The transplantation and in situ injection experiments verified that loss of CDC42 impeded root extension via inhibiting the proliferation and differentiation of DPCs. CONCLUSIONS: We innovatively revealed that CDC42 was responsible for guiding root elongation in a mesenchyme-specific manner. Furthermore, CDC42-mediated canonical Wnt signaling regulated odontogenic differentiation of DPCs during root formation.

Epigenetic regulation of mesenchymal stem cell aging through histone modifications.

Stem cell senescence and exhaustion, a hallmark of aging, lead to declines in tissue repair and regeneration in aged individuals. Emerging evidence has revealed that epigenetic regulation plays critical roles in the self-renew, lineage-commitment, survival, and function of stem cells. Moreover, epigenetic alterations are considered important drivers of stem cell dysfunction during aging. In this review, we focused on current knowledge of the histone modifications in the aging of mesenchymal stem cells (MSCs). The aberrant epigenetic modifications on histones, including methylation and acetylation, have been found in aging MSCs. By disturbing the expression of specific genes, these epigenetic modifications affect the self-renew, survival, and differentiation of MSCs. A set of epigenetic enzymes that write or erase these modifications are critical in regulating the aging of MSCs. Furthermore, we discussed the rejuvenation strategies based on epigenetics to prevent stem cell aging and/or rejuvenate senescent MSCs.

NCOA7 Regulates Growth and Metastasis of Clear Cell Renal Cell Carcinoma via MAPK/ERK Signaling Pathway.

NCOA7 is a nuclear receptor coactivator that is downregulated in a variety of cancers. However, the expression and prognostic significance of NCOA7 in clear cell renal cell carcinoma (ccRCC) remain unknown. The expression of NCOA7 in ccRCC tissues was analyzed using bioinformatics analysis, Western blotting, and immunohistochemistry. Kaplan-Meier analysis, the receiver operating characteristic (ROC) curve, and clinicopathological correlation analysis were used to assess the predictive power of NCOA7. Overexpression function tests were conducted in cells and mouse models to clarify the function and mechanism of NCOA7 in inhibiting the progression of ccRCC. NCOA7 expression was downregulated in all three subtypes of renal cell carcinoma, and only had significant prognostic value for patients with ccRCC. NCOA7 overexpression inhibited the proliferation, invasion, and metastasis of ccRCC cells in vivo and in vitro. Mechanistically, NCOA7 inhibited the MAPK/ERK pathway to regulate epithelial-mesenchymal transformation (EMT) and apoptosis, thereby inhibiting the progression of ccRCC. NCOA7 inhibits tumor growth and metastasis of ccRCC through the MAPK/ERK pathway, thus indicating its potential as a prognostic marker and therapeutic target for ccRCC.

Risk factors for BK virus infection in DCD donor kidney transplant recipients.

Background: BK virus infection after kidney transplantation can negatively impact the prognosis of patients. However, current risk factor analyses primarily focus on BK virus nephropathy, while BK viruria and BK viruria progressing to BK viremia receive less attention. This study aims to analyze the risk factors associated with BK viruria and BK viruria progressing to BK viremia in recipients of donation after cardiac death (DCD), with the goal of facilitating early intervention. Methods: Donor characteristics and clinical data of recipients before and after transplantation were evaluated, and logistic univariate and multivariate analyses were performed to determine the risk factors associated with BK viruria and the progression of BK viruria to BK viremia. Additionally, machine learning techniques were employed to identify the top five features associated with BK viruria evolving into BK viremia. Results: During a median follow-up time of 1,072 days (range 739-1,418), 69 transplant recipients (15.6% incidence rate) developed BK viruria after transplantation, with 49.3% of cases occurring within 6 months post-transplantation. Moreover, 19 patients progressed to BK viremia. Donor age [OR: 1.022 (1.000, 1.045), p = 0.047] and donor procalcitonin (PCT) levels [0.5-10 ng/ml; OR: 0.482 (0.280, 0.828), p = 0.008] were identified as independent risk factors for BK viruria. High BK viruria [OR: 11.641 (1.745, 77.678), p = 0.011], recipient age [OR: 1.106 (1.017, 1.202), p = 0.018], and immunoinduction regimen [ATG; OR: 0.063 (0.006, 0.683), p = 0.023] were independent risk factors for BK viruria progressing to BK viremia. Machine learning analysis confirmed the importance of high BK viruria, recipient age, and immunoinduction regimen (ATG) in predicting the progression of BK viruria to BK viremia. Conclusion: The development and progression of BK virus in DCD kidney transplant recipients is influenced by multiple factors. Early intervention and treatment could potentially extend the lifespan of the transplanted organ.

Glymphatic Dysfunction in Migraine Mice Model.

The glymphatic system is important for waste removal in the central nervous system. It removes soluble proteins and metabolic waste under the action of aquaporin-4 (AQP4) at the end of astrocytes. The glymphatic system plays a role in numerous neurological diseases; however, the relationship between migraine and the glymphatic system remains unclear. In this study, we explored the relationship between the glymphatic system and migraine using the nitroglycerin migraine model in C57/BL6mice. The glymphatic influx of cerebrospinal fluid tracer was reduced in mice in the migraine model, accompanied by decreased expression and impaired polarization of AQP4, thereby suggesting glymphatic dysfunction in migraine mice model. Then, further suppression of glymphatic function by TGN-020 (an AQP4 blocker) aggravated the migraine pathological changes in mice. The results indicated that glymphatic dysfunction may aggravate migraine pathology. Therefore, our findings revealed the potential role of the glymphatic system in migraine, providing possible targets for migraine prevention and treatment.