Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury.

JOURNAL/nrgr/04.03/01300535-202502000-00034/figure1/v/2024-05-28T214302Z/r/image-tiff Several studies have found that transplantation of neural progenitor cells (NPCs) promotes the survival of injured neurons. However, a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application. Small extracellular vesicles (sEVs) contain bioactive molecules for neuronal protection and regeneration. Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases. In this study, we intravitreally transplanted sEVs derived from human induced pluripotent stem cells (hiPSCs) and hiPSCs-differentiated NPCs (hiPSC-NPC) in a mouse model of optic nerve crush. Our results show that these intravitreally injected sEVs were ingested by retinal cells, especially those localized in the ganglion cell layer. Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration, and regulated the retinal microenvironment by inhibiting excessive activation of microglia. Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells, which had protective effects on RGCs after optic nerve injury. These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

High-Throughput Transcriptomic Analysis of Circadian Rhythm of Chlorophyll Metabolism under Different Photoperiods in Tea Plants.

Tea plants are a perennial crop with significant economic value. Chlorophyll, a key factor in tea leaf color and photosynthetic efficiency, is affected by the photoperiod and usually exhibits diurnal and seasonal variations. In this study, high-throughput transcriptomic analysis was used to study the chlorophyll metabolism, under different photoperiods, of tea plants. We conducted a time-series sampling under a skeleton photoperiod (6L6D) and continuous light conditions (24 L), measuring the chlorophyll and carotenoid content at a photoperiod interval of 3 h (24 h). Transcriptome sequencing was performed at six time points across two light cycles, followed by bioinformatics analysis to identify and annotate the differentially expressed genes (DEGs) involved in chlorophyll metabolism. The results revealed distinct expression patterns of key genes in the chlorophyll biosynthetic pathway. The expression levels of CHLE (magnesium-protoporphyrin IX monomethyl ester cyclase gene), CHLP (geranylgeranyl reductase gene), CLH (chlorophyllase gene), and POR (cytochrome P450 oxidoreductase gene), encoding enzymes in chlorophyll synthesis, were increased under continuous light conditions (24 L). At 6L6D, the expression levels of CHLP1.1, POR1.1, and POR1.2 showed an oscillating trend. The expression levels of CHLP1.2 and CLH1.1 showed the same trend, they both decreased under light treatment and increased under dark treatment. Our findings provide potential insights into the molecular basis of how photoperiods regulate chlorophyll metabolism in tea plants.

Insights into the molecular network characteristics of major HIV-1 subtypes in developed Eastern China: a study based on comprehensive molecular surveillance data.

PURPOSE: This study aimed to conduct a comprehensive molecular epidemiology study of major HIV-1 subtypes in developed Eastern China (Zhejiang Province). METHODS: Plasma samples and epidemiological information were collected from 4180 newly diagnosed HIV-1 positive patients in Zhejiang Province in 2021. Pol sequences were obtained to determine the subtypes via multiple analytical tools. HIV-1 molecular networks were constructed on the basis of genetic distances to analyze transmission patterns among major subtypes. Furthermore, the birth-death skyline (BDSKY) model was utilized to estimate the transmission risks associated with large clusters (LCs). RESULTS: In 4180 patients, 3699 (88.49%) pol sequences were successfully obtained and classified into four subtype groups. In the networks under an optimal genetic distance of 0.01 substitutions/site, the majority of links (74.52%, 1383/1856) involved individuals within the same city, highlighting the predominant role of local transmission in driving the HIV-1 epidemic. In the CRF07_BC, CRF01_AE, and others/URFs networks, men who have sex with men (MSM) were the primary sexual transmission population, with the younger MSM group (< 30 years old) exhibiting higher linkage frequencies. Within the CRF08_BC network, 93.98% of individuals were infected primarily through heterosexual contact and had a significantly greater risk of localized clustering than other subtypes did. Moreover, fifteen identified LCs were predominantly transmitted through commercial heterosexual contact (CHC), exhibiting localized clustering and high potential for sustained diffusion. CONCLUSIONS: Overall, our findings reveal a diverse and heterogeneous distribution of HIV-1 subtypes in Zhejiang Province, with noticeable variations in hotspots across different geographic areas and populations.

Decision fatigue experience of front-line nurses in the context of public health emergency: an interpretative phenomenological analysis.

BACKGROUND: Decision fatigue is a new concept in the field of psychology and refers to a state of fatigue alongside impaired cognitive processing and emotional regulation ability. Previous studies have confirmed that nurses are prone to decision fatigue, and nurses who experience decision fatigue may implement nursing measures that are inconsistent with clinical evidence, thus affecting patients' benefits. COVID-19, as a large-scale global public health emergency, increased the workload and burden of nurses and aggravated decision fatigue. However, the factors leading to decision fatigue among nurses have not yet been identified. METHODS: This study is guided by interpretative phenomenology. During the epidemic period of COVID-19: From November 2022 to February 2023, a one-to-one, semi-structured in-depth interview was conducted among nurses with decision fatigue experience who were participating in front-line work in Jilin Province using homogenous sampling. The interview recordings and related data were transcribed into text within 24 h, and data analysis was assisted by NVivo 12.0 software. RESULTS: After a total of 14 front-line nurses were analyzed in this study, The thematic level reaches saturation, the findings present a persuasive and coherent narrative, and the study is terminated, and finally extracted and formed three core themes: "Cognition, influence and attitude of decision fatigue", "Approaching factors of decision fatigue" and "Avoidant factors of decision fatigue". CONCLUSION: This study confirmed that decision fatigue was widespread in the work of front-line nurses, affecting the physical and psychological health of nurses, the quality of nursing work, the degree of benefit of patients and the clinical outcome. However, nursing staff do not know enough about decision fatigue, so the popularization and research of decision fatigue should be strengthened. Improve the attention of medical institutions, nursing managers and nursing staff.Some suggestions are put forward for the intervention of decision fatigue through personnel, task, tool and technology, organization and environment.

Association between adherence to life's simple 7 metrics and risk of obstructive sleep apnea among adults in the United States.

BACKGROUND: We aimed to explore the impact of adherence to Life's Simple 7 (LS7) metrics on risk of obstructive sleep apnea (OSA), and the impact of inflammation on the association, in adults in the United States. METHODS: Data from 13,825 community-dwelling adults aged ≥ 20 years recruited in the National Health and Nutrition Examination Surveys (NHANES) 2005-2008, 2015-2018 was analyzed. The LS7 score was calculated based on the AHA definition of LS7 metrics. The diagnosis of OSA was based on self-reported symptoms of sleep disturbance using a standard questionnaire. The Multivariable Apnea Prediction (MAP) Index score was also calculated to assess the risk of OSA. Log-binominal regression and negative binomial regression were performed to estimate the associations between LS7 and OSA and MAP index, with odds ratios (ORs) and prevalence ratios (PRs) and their 95% confidence intervals (CIs) calculated. Mediation analysis was performed to estimate the mediating effects of inflammatory indicators on the associations. RESULTS: A total of 4473 participants (32.4%) had OSA, and the mean MAP index was 0.39. In fully adjusted log-binominal regression models, with total score < 6 as the reference, the ORs (95% CIs) for risk of OSA were 0.90 (0.73, 1.10), 0.76 (0.65, 0.89), 0.78 (0.64, 0.95), and 0.45 (0.38, 0.54) for total score = 6, total score = 7, total score = 8, and total score > 8, respectively (P for trend < 0.001). When LS7 score was analyzed as a continuous variable, each 1-point increase in LS7 score was associated with a 15% decrease in OSA risk (P < 0.001). In negative binominal regression models, the adjusted PRs (95% CIs) for the MAP index were 0.93 (0.90, 0.97), 0.87 (0.84, 0.91), 0.80 (0.77, 0.84), and 0.55 (0.53, 0.57) for total score = 6, total score = 7, total score = 8, and total score > 8, respectively (P for trend < 0.001). For each 1-point increase in LS7 score, the risk of OSA decreased by 13% (P < 0.001). Consistent results were observed in subgroup analysis. Mediation analysis indicated that inflammatory factors, including blood cell count, neutrophil count, and C-reactive protein, positively mediated the association of LS7 with OSA, with a mediation proportion of 0.022 (P = 0.04), 0.02 (P = 0.04), and 0.02 (P = 0.02), respectively. CONCLUSIONS: In a nationally representative sample of US adults, adherence to LS7 metrics was independently associated with reduced OSA risk. Inflammation plays a mediating role in the association between LS7 and OSA.

Molecular transmission network analysis reveals the challenge of HIV-1 in ageing patients in China: elderly people play a crucial role in the transmission of subtypes and high pretreatment drug resistance in developed Eastern China, 2019-2023.

BACKGROUND: The number and proportion of HIV/AIDS patients among older people are continuously and rapidly increasing in China. We conducted a detailed molecular epidemiological analysis of HIV-1 epidemic strains in a developed city in eastern China and found that elderly people play a crucial role in the transmission of subtypes and high pretreatment drug resistance (PDR). METHODS: A total of 1048 samples were obtained from 1129 (92.8%) newly confirmed HIV-1-positive and treatment-naive patients between 2019 and 2023. The 1316 bp target fragment of the pol gene was amplified by reverse transcription polymerase chain reaction (RT‒PCR) and nested PCR, and Maximum-likelihood (ML) phylogenetic trees and molecular transmission network were constructed to analyse the subtypes and transmission clusters. Molecular transmission network was visualized using Cytoscape with the distance threshold of 0.0075. PDR-associated mutations were determined according to the Stanford University HIV Drug Resistance Database. RESULTS: A total of 933 pol sequences (89.0%, 933/1048) were successfully obtained, and twelve HIV-1 subtypes were detected. CRF07_BC was the predominant subtype, accounting for 48.1% (449/933) of sequences, followed by CRF01_AE (29.4%, 274/933). A total of 398 individuals (42.7%, 398/933) formed 89 clusters in the network. Multivariable logistic regression analysis revealed that age, nationality, subtype, and PDR were the most significant factors associated with clustering in the transmission network. The prevalence of PDR was 14.6% (136/933).PDR associated with non-nucleoside reverse transcriptase inhibitors (10.0%, 93/933) was much more common than that associated with nucleoside reverse transcriptase inhibitors (1.8%, 17/933) and protease inhibitors (3.2%, 30/933) (χ2 = 77.961, p < 0.001). The most frequent NNRTI mutations were K103N/S/KN/NS (52.2%, 71/136), which led to the highest proportion of high-level resistance to nevirapine and efavirenz (52.2%). CONCLUSIONS: Our study revealed the important influence of elderly people on CRF07_BC transmission and the high prevalence of PDR. The clustering of drug-resistant cases was significant, which suggested the potential for localized widespread transmission of drug-resistant strains. HIV screening and the determination of PDR are recommended for older patients to improve early detection and reduce treatment failure and second-generation transmission.

Prognostic factors of patients with human epidermal growth factor receptor 2-positive breast cancer following neoadjuvant therapy: Development and validation of a predictive nomogram.

OBJECTIVE: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer exhibits an aggressive phenotype and poor prognosis. The application of neoadjuvant therapy (NAT) in patients with breast cancer can significantly reduce the risks of disease recurrence and improve survival. By integrating different clinicopathological factors, nomograms are valuable tools for prognosis prediction. This study aimed to assess the prognostic value of clinicopathological factors in patients with HER2-positive breast cancer and construct a nomogram for outcome prediction. METHODS: We retrospectively analyzed the clinicopathological data from 374 patients with breast cancer admitted to the Fourth Hospital of Hebei Medical University between January 2009 and December 2017, who were diagnosed with invasive breast cancer through preoperative core needle biopsy pathology, underwent surgical resection after NAT, and were HER2-positive. Patients were randomly divided into a training and validation set at a ratio of 7:3. Univariate and multivariate survival analyses were performed using Kaplan-Meier and Cox proportional hazards regression models. Results of the multivariate analysis were used to create nomograms predicting 3-, 5-, and 8-year overall survival (OS) rates. Calibration curves were plotted to test concordance between the predicted and actual risks. Harrell C-index and time-dependent receiver operating characteristic (ROC) curves were used to evaluate the discriminability of the nomogram prediction model. RESULTS: All included patients were women, with a mean age of 50 ± 10.4 years (range: 26-72 years). In the training set, both univariate and multivariate analyses identified residual cancer burden (RCB) class, tumor-infiltrating lymphocytes(TILs), and clinical stage as independent prognostic factors for OS, and these factors were combined to construct a nomogram. The calibration curves demonstrated good concordance between the predicted and actual risks, and the C-index of the nomogram was 0.882 (95 % CI 0.863-0.901). The 3-, 5-, and 8-year areas under the ROC curve (AUCs) were 0.909, 0.893, and 0.918, respectively, indicating good accuracy of the nomogram. The calibration curves also demonstrated good concordance in the validation set, with a C-index of 0.850 (95 % CI 0.804-0.896) and 3-, 5-, and 8-year AUCs of 0.909, 0.815, and 0.834, respectively, which also indicated good accuracy. CONCLUSION: The nomogram prediction model accurately predicted the prognostic status of post-NAT patients with breast cancer and was more accurate than clinical stage and RCB class. Therefore, it can serve as a reliable guide for selecting clinical treatment measures for breast cancer.

The role of mesenchymal stem cells in cancer and prospects for their use in cancer therapeutics.

Mesenchymal stem cells (MSCs) are recruited by malignant tumor cells to the tumor microenvironment (TME) and play a crucial role in the initiation and progression of malignant tumors. This role encompasses immune evasion, promotion of angiogenesis, stimulation of cancer cell proliferation, correlation with cancer stem cells, multilineage differentiation within the TME, and development of treatment resistance. Simultaneously, extensive research is exploring the homing effect of MSCs and MSC-derived extracellular vesicles (MSCs-EVs) in tumors, aiming to design them as carriers for antitumor substances. These substances are targeted to deliver antitumor drugs to enhance drug efficacy while reducing drug toxicity. This paper provides a review of the supportive role of MSCs in tumor progression and the associated molecular mechanisms. Additionally, we summarize the latest therapeutic strategies involving engineered MSCs and MSCs-EVs in cancer treatment, including their utilization as carriers for gene therapeutic agents, chemotherapeutics, and oncolytic viruses. We also discuss the distribution and clearance of MSCs and MSCs-EVs upon entry into the body to elucidate the potential of targeted therapies based on MSCs and MSCs-EVs in cancer treatment, along with the challenges they face.

Full-Spectrum Surveillance of Pre-Treatment HIV Drug Resistance in Southeastern China.

HIV drug resistance compromises the ability of anti-retroviral therapy (ART) to suppress viral replication, resulting in treatment failure. This study investigates the prevalence of pre-treatment drug resistance (PDR) in newly diagnosed individuals in a prosperous city (Wenzhou) in Southeastern China. A cross-sectional investigation was carried out among 473 newly diagnosed ART-naive HIV-1-infected individuals between January and December 2022. The protease-reverse transcriptase (PR-RT) region and integrase (IN) region of HIV-1 were amplified by two separately nested PCRs, followed by sequencing. Drug resistance mutations (DRMs) and drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were analyzed. The PDR prevalence was 6.5% [95% CI: 4.4-9.1] for any anti-retroviral drug, 0.9% [95% CI: 0.3-2.3] for NRTIs, 4.1% [95% CI: 2.5-6.5] for NNRTIs, 1.8% [95% CI: 0.8-3.6] for PIs and 0.5% [95% CI: 0.1-1.8] for INSTIs. According to the subtyping results of the PR-RT region, 11 different subtypes and 31 unique recombinant forms (URFs) were found. CRF07_BC was the dominant subtype (53.7%, 233/434), followed by CRF01_AE (25.3%, 110/434). V179D (1.6%) and K103N (1.4%) were the most predominant types of NNRTI DRMs. Q58E (1.2%) and M184V (0.7%) were the most frequent PI DRMs and NRTI DRMs, respectively. The INSTI-related DRMs Y143S (causes high-level resistance to RAL) and G163K (causes low-level resistance to EVG and RAL) were found in one patient each. Given the relatively high PDR prevalence of NNRTI (4.1%), non-NNRTI-based ART may be preferred in the future. It is recommended to include genotypic resistance testing before starting ART in regions where feasible.

A dual-response ratiometric fluorescent sensor by europium-doped silicon nanoparticles for fluorescent and smartphone imaging detection of tetracycline.

Given the threat to human health posed by the abuse of tetracycline (TC), the development of a portable, on-site methods for highly sensitive and rapid TC detection is crucial. In this work, we initially synthesized europium-doped silicon nanoparticles (SiEuNPs) through a facile one-pot microwave-assisted method. Due to its blue-red dual fluorescence emission (465 nm/621 nm), which was respectively attributed to the silicon nanoparticles and Eu3+, SiEuNPs were designed as a ratiometric fluorescent sensor for TC detection. For the dual-signal reverse response mechanism: TC quenched the blue emission from silicon nanoparticles through inner filter effect (IFE), and enhanced the red emission through "antenna effect" (AE) between TC and Eu3+, the nanoprobe was able to detect TC within a range of 0.2-10 µM with a limit of detection (LOD) of 10.7 nM. Notably, the equilibrium detection time was only 1 min, achieving rapid TC detection. Furthermore, TC was also measured in real samples (tap water, milk and honey) with recoveries ranging from 95.7 % to 117.0 %. More importantly, a portable smartphone-assisted on-site detection platform was developed, enabling real-time qualitative identification and semi-quantitative analysis of TC based on fluorescence color changes. This work not only provided a novel doped silicon nanoparticles strategy, but also constructed a ratiometric sensing platform with dual-signal reverse response for intuitive and real-time TC detection.

Radiomics models of contrast-enhanced computed tomography for predicting the activity and prognosis of acute pancreatitis.

BACKGROUND: The modified pancreatitis activity scoring system (mPASS) was proposed to assess the activity of acute pancreatitis (AP) while it doesn't include indicators that directly reflect pathophysiology processes and imaging characteristics. OBJECTIVES: To determine the threshold of admission mPASS and investigate radiomics and laboratory parameters to construct a model to predict the activity of AP. METHODS: AP inpatients at institution 1 were randomly divided into training and validation groups based on a 5:5 ratio. AP inpatients at Institution 2 were served as test group. The cutoff value of admission mPASS scores in predicting severe AP was selected to divide patients into high and low level of disease activity group. LASSO was used in screening features. Multivariable logistic regression was used to develop radiomics model. Meaningful laboratory parameters were used to construct combined model. RESULTS: There were 234 (48 years ± 10, 155 men) and 101 (48 years ± 11, 69 men) patients in two institutions. The threshold of admission mPASS score was 112.5 in severe AP prediction. The AUC of the radiomics model was 0.79, 0.72, and 0.76 and that of the combined model incorporating rad-score and white blood cell were 0.84, 0.77, and 0.80 in three groups for activity prediction. The AUC of the combined model in predicting disease without remission was 0.74. CONCLUSIONS: The threshold of admission mPASS was 112.5 in predicting severe AP. The model based on CECT radiomics has the ability to predict AP activity. Its ability to predict disease without remission is comparable to mPASS. CRITICAL RELEVANCE STATEMENT: This work is the first attempt to assess the activity of acute pancreatitis using contrast-enhanced CT radiomics and laboratory parameters. The model provides a new method to predict the activity and prognosis of AP, which could contribute to further management. KEY POINTS: Radiomics features and laboratory parameters are associated with the activity of acute pancreatitis. The combined model provides a new method to predict the activity and prognosis of AP. The ability of the combined model is comparable to the modified Pancreatitis Activity Scoring System.

Three dyes for use in tissue marking inks for biopsies and other small specimens.

In histological processing, the loss of a small biopsies can prevent diagnosis by the pathologist. Appropriate specimen marking dyes are helpful, but those sold for the purpose have trade-secret components. The purpose of this study is to find suitable dyes with known chemistry to improve the visibility of small specimens. Samples of various organs, including stomach, lung, nasopharynx, small intestine and sentinel lymph nodes, were labeled with Rose red D-FR (CI 282855, Direct red 227), Blue 2RL (CI 24315, Direct blue 80), and Purple D-5BL (CI 29120, Direct violet 66). Clinical pathologists evaluated the dyeing capability and determined any interference of the marking dyes with diagnosis of stained sections. Direct red 227, Direct blue 80, and Direct violet 66 all increased the visibility of small specimens, without interfering with hematoxylin & eosin (HE) staining or immunohistochemistry. All three dyes can therefore be recommended for marking small specimens such as biopsies.

Plasma proteomics analysis of Chinese HIV-1 infected individuals focusing on the immune and inflammatory factors afford insight into the viral control mechanism.

Background: Long-term non-progressors (LTNPs) with HIV infection can naturally control viral replication for up to a decade without antiretroviral therapy (ART), but the underlying mechanisms of this phenomenon remain elusive. Methods: To investigate the relevant immune and inflammatory factors associated with this natural control mechanism, we collected plasma samples from 16 LTNPs, 14 untreated viral progressors (VPs), 17 successfully ART-treated patients (TPs), and 16 healthy controls (HCs). The OLINK immune response panel and inflammation panel were employed to detect critical proteins, and the plasma neutralizing activity against a global panel of pseudoviruses was assessed using TZM-bl cells. Results: The combination of IL17C, IL18, DDX58, and NF2 contributed to discriminating LTNPs and VPs. IL18 and CCL25 were positively associated with CD4+ T cell counts but negatively correlated with viral load. Furthermore, CXCL9 and CXCL10 emerged as potential supplementary diagnostic markers for assessing the efficacy of antiretroviral therapy (ART). Finally, TNFRSF9 displayed positive correlations with neutralization breadth and Geometry Median Titer (GMT) despite the lack of significant differences between LTNPs and VPs. Conclusion: In summary, this study identified a set of biomarkers in HIV-infected individuals at different disease stages. These markers constitute a potential network for immune balance regulation in HIV infection, which is related to the long-term control of HIV by LTNPs. It provides important clues for further exploring the immune regulatory mechanism of HIV.

Ultrasound and computed tomography angiography diagnosis of fetal right atrial isomerism with cardiac total anomalous pulmonary venous connection and intestinal malrotation: a case report and literature review.

Right atrial isomerism is a rare and severe isomerism. It is frequently associated with complex congenital heart disease and various extracardiac anomalies. Imaging diagnosis of right atrial isomerism is a challenge. Multisystem and complex anomalies in a 24-week-old fetus were diagnosed with prenatal ultrasound, postnatal computed tomography angiography (CTA), and autopsy. The ultrasound detected most major cardiovascular anomalies including right atrial isomerism and total anomalous pulmonary venous connection. The CTA further detected thoracic and abdominal malformations such as bilateral morphologically right bronchus, diaphragmatic hernia, asplenia, midline liver, and intestinal malrotation. The autopsy confirmed both ultrasound and CTA findings with additional findings, namely, bilateral trilobed lungs and bilateral morphological right auricles. Prenatal ultrasound and postnatal CTA can be complementary to each other in detecting multi-system complex anomalies. Their combined use can be useful for prenatal counseling and postpartum management.

High molecular weight hyaluronic acid-liposome delivery system for efficient transdermal treatment of acute and chronic skin photodamage.

Photodamage is one of the most common causes of skin injury. High molecular weight hyaluronic acid (HHA) has shown immense potential in the treatment of skin photodamage by virtue of its anti-inflammatory, reparative, and antioxidative properties. However, due to its large molecular structure of HHA, HHA solution could only form a protective film on the skin surface in conventional application, failing to effectively penetrate the skin, which necessitates the development of new delivery strategies. Liposomes, with a structure similar to biological membranes, have garnered extensive attention as transdermal drug delivery carriers because of their advantages in permeability, dermal compatibility, and biosafety. Herein, we have developed a HHA-liposome transdermal system (HHL) by embedding HHA into the liposome structure using reverse evaporation, high-speed homogenization, and micro-jet techniques. The effective penetration and long-term residence of HHA in skin tissue were multidimensionally verified, and the kinetics of HHA in the skin were extensively studied. Moreover, it was demonstrated that HHL significantly strengthened the activity of human keratinocytes and effectively inhibits photo-induced cellular aging in vitro. Furthermore, a murine model of acute skin injury induced by laser ablation was established, where the transdermal system showed significant anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair, thereby demonstrating immense potential in accelerating skin wound healing. Meanwhile, HHL significantly ameliorated skin barrier dysfunction caused by simulated sunlight exposure, inhibited skin erythema, inflammatory responses, and oxidative stress, and promoted collagen expression in a chronic photodamage skin model. Therefore, this transdermal delivery system with biocompatibility represents a promising new strategy for the non-invasive application of HHA in skin photodamage, revealing the significant potential for clinical translation and broad application prospects. STATEMENT OF SIGNIFICANCE: The transdermal system utilizing hyaluronic acid-based liposomes enhances skin permeability and retains high molecular weight hyaluronic acid (HHL). In vitro experiments with human keratinocytes demonstrate significant skin repair effects of HHL and its effective inhibition of cellular aging. In an acute photodamage model, HHL exhibits stronger anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair. In a chronic photodamage model, HHL significantly improves skin barrier dysfunction, reduces oxidative stress induced by simulated sunlight, and enhances collagen expression.

HBV and HCV Co-Infection in Chinese Newly Diagnosed HIV+ Subjects in 2015 and 2023: A Cross-Sectional Study.

With shared routes of transmission, HBV and HCV co-infection are estimated to occur more in subjects with HIV. This study aimed to characterize and describe the prevalence of HBV and HCV co-infections in a cohort of newly diagnosed HIV+ subjects living in China. We conducted a cross-sectional study among newly diagnosed HIV+ subjects aged 18-100 who participated in surveys on the national HIV molecular epidemiology in 2015 and 2023. (The epidemiological table survey is located in the national database alongside serologic testing). The chi-square test was used to identify changes in infections between the studying populations in 2015 and 2023, and conditional logistic regression models were fit to identify risk factors for each co-infection. Among the 11,024 newly diagnosed HIV+ subjects who were surveyed (n = 4501 in 2015; n = 6523 in 2023), the prevalence of HBV, HCV, and HBV/HCV in 2023 was lower than that in 2015, respectively. No decrease was observed in HCV co-infection in men who had sex with men (MSM) in North China, Northeast China, and East China. Increasing recognition among those at high risk of heterosexual transmission and those with low educational backgrounds is paramount to the prevention and control of HIV/HBV/HCV infections.

Circadian rhythm response and its effect on photosynthetic characteristics of the Lhcb family genes in tea plant.

BACKGROUND: The circadian clock, also known as the circadian rhythm, is responsible for predicting daily and seasonal changes in the environment, and adjusting various physiological and developmental processes to the appropriate times during plant growth and development. The circadian clock controls the expression of the Lhcb gene, which encodes the chlorophyll a/b binding protein. However, the roles of the Lhcb gene in tea plant remain unclear. RESULTS: In this study, a total of 16 CsLhcb genes were identified based on the tea plant genome, which were distributed on 8 chromosomes of the tea plant. The promoter regions of CsLhcb genes have a variety of cis-acting elements including hormonal, abiotic stress responses and light response elements. The CsLhcb family genes are involved in the light response process in tea plant. The photosynthetic parameter of tea leaves showed rhythmic changes during the two photoperiod periods (48 h). Stomata are basically open during the day and closed at night. Real-time quantitative PCR results showed that most of the CsLhcb family genes were highly expressed during the day, but were less expressed at night. CONCLUSIONS: Results indicated that CsLhcb genes were involved in the circadian clock process of tea plant, it also provided potential references for further understanding of the function of CsLhcb gene family in tea plant.

TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin.

Hepatitis B virus (HBV) infection poses a significant burden on global public health. Unfortunately, current treatments cannot fully alleviate this burden as they have limited effect on the transcriptional activity of the tenacious covalently closed circular DNA (cccDNA) responsible for viral persistence. Consequently, the HBV life cycle should be further investigated to develop new anti-HBV pharmaceutical targets. Our previous study discovered that the host gene TMEM203 hinders HBV replication by participating in calcium ion regulation. The involvement of intracellular calcium in HBV replication has also been confirmed. In this study, we found that transient receptor potential vanilloid 4 (TRPV4) notably enhances HBV reproduction by investigating the effects of several calcium ion-related molecules on HBV replication. The in-depth study showed that TRPV4 promotes hepatitis B core/capsid protein (HBc) protein stability through the ubiquitination pathway and then promotes the nucleocapsid assembly. HBc binds to cccDNA and reduces the nucleosome spacing of the cccDNA-histones complex, which may regulate HBV transcription by altering the nucleosome arrangement of the HBV genome. Moreover, our results showed that TRPV4 promotes cccDNA-dependent transcription by accelerating the methylation modification of H3K4. In conclusion, TRPV4 could interact with HBV core protein and regulate HBV during transcription and replication. These data suggest that TRPV4 exerts multifaceted HBV-related synergistic factors and may serve as a therapeutic target for CHB.

High TPX2 expression results in poor prognosis, and Sp1 mediates the coupling of the CX3CR1/CXCL10 chemokine pathway to the PI3K/Akt pathway through targeted inhibition of TPX2 in endometrial cancer.

INTRODUCTION: Approximately 30% of individuals with advanced EC have unsatisfactory prognosis. Evidence suggests that TPX2 is frequently upregulated in malignancies and related to cancer progression. Its role and pathological mechanism in EC need further research. METHODS: GSEA and TPX2 expression, GO, KEGG, and prognostic analyses were performed with TCGA data by bioinformatic approaches. Relationships between TPX2 expression and clinicopathological parameters were investigated immunohistochemically and statistically. shRNA and overexpression plasmids were constructed and transfected into AN3CA and Ishikawa cells to evaluate phenotypic changes and injected into nude mouse axillae. Coimmunoprecipitation and chromatin immunoprecipitation were used to identify interacting proteins and promoter-binding sequences. Changes in TPX2 expression were identified by Western blotting and RT-qPCR. RESULTS: TPX2 expression was significantly higher in EC tissues than in normal tissues in TCGA and in-house specimens (all p < 0.001). In survival analysis, high TPX2 expression was associated with poor prognosis (p = 0.003). TPX2 overexpression stimulated cancer cell proliferation, promoted the G0-G1-to-G2/M transition, enhanced invasion and migration, and accelerated tumor growth in nude mice. TPX2 regulated the CX3CR1/CXCL10 chemokine pathway and activated the PI3K/Akt signaling pathway. Sp1 negatively regulated TPX2 expression, affecting the malignant progression of endometrial cancer cells by coupling the CX3CR1/CXCL10 chemokine pathway to the PI3K/Akt signaling pathway. CONCLUSION: TPX2 could be a prognostic biomarker for EC and play an important role in the CX3CR1/CXCL10 chemokine pathway and PI3K/Akt pathway via Sp1.

Effect of suspended particulate matter on physiological, biochemical and photosynthetic characteristics of Chlorella pyrenoidosa in the Jinjiang Estuary (Fujian, China).

Suspended particulate matter (SPM), an important component of the natural water environment, can act as a carrier of many pollutants that affect aquatic organisms. In the present study, the effect of SPM obtained from Jinjiang Estuary on the physiological, biochemical, and photosynthetic properties of typical freshwater algae (Chlorella pyrenoidosa) was investigated. The results showed that under different concentrations of SPM treatment, the superoxide dismutase (SOD), catalase (CAT) activities, and malondialdehyde (MDA) content of C. pyrenoidosa increased, but the soluble protein content decreased. SPM with different particle sizes had less effect on SOD of C. pyrenoidosa, but showed a promoting effect on CAT and MDA as well as soluble protein content. In terms of photosynthetic activity, high concentrations (70, 90 mg/L) and small particle sizes (0-75, 75-120 µm) of SPM had a greater effect on the chlorophyll a content of C. pyrenoidosa. In addition, different concentrations of SPM had no significant effect on the potential photosynthetic activity of PS II (Fv/F0) and the maximum quantum yield of PS II (Fv/Fm), but the inhibition of the initial slope (alpha), the maximum photosynthetic rate (ETRmax) and the semi-light saturation point (Ik) increased with the increase of SPM concentration. Fv/F0, ETRmax, and Ik of C. pyrenoidosa showed some degree of recovery after inhibition in the presence of SPM of different particle sizes.