Panax ginseng extract prevents UVB-induced skin photodamage by modulating VMP1-mediated ER stress.

BACKGROUND: The endoplasmic reticulum (ER) stress is a crucial toxic signaling event triggered by chronic exposure to Ultraviolet B radiation (UVB), which significantly exacerbate photodamage responses in the irradiated skin. Therefore, the identification of agents capable of inhibiting ER stress could serve as a promising therapeutic strategy for addressing the unmet clinical needs in the treatment of UVB-induced photodamage. METHODS: A UVB-irradiated mouse model was used and topical administration of Panax ginseng extract was carried out for a duration of 9 weeks. Vitamin E was used as a positive control. After 9 weeks of administration, the skin appearance, epidermal hyperplasia, infiltration of inflammatory cells, apoptosis, and collagen content were measured. The keratinocytes were irradiated with 6 mJ/cm2 UVB to establish an in vitro model. The levels of ER stress and apoptosis were investigated both in vivo and in vitro using qRT-PCR, immunoblotting, and immunofluorescence. RESULTS: Among the 14 extracts derived from 13 distinct plant species that were screened, Panax ginseng, Prunus mume, and Camellia japonica showed inhibitory effect on UVB-induced ER stress. Notably, Panax ginseng effectively inhibits collagen degradation and apoptosis in both irradiated keratinocytes and Balb/C mice skin. Furthermore, the silencing of VMP1 significantly impeded the cellular protective effect of Panax ginseng extract on UVB-irradiated keratinocytes, indicating that Panax ginseng exerts its protective effects through targeted promotion of VMP1. CONCLUSION: Our data suggest that Panax ginseng extract possess a therapeutical effect on UVB radiation-induced photodamage by promoting VMP1-mediated inhibition of ER stress.

A multifunctional composite scaffold responds to microenvironment and guides osteogenesis for the repair of infected bone defects.

Treating bone defect concomitant with microbial infection poses a formidable clinical challenge. Addressing this dilemma necessitates the implementation of biomaterials exhibiting dual capabilities in anti-bacteria and bone regeneration. Of particular significance is the altered microenvironment observed in infected bones, characterized by acidity, inflammation, and an abundance of reactive oxygen species (ROS). These conditions, while challenging, present an opportunity for therapeutic intervention in the context of contaminated bone defects. In this study, we developed an oriented composite scaffold containing copper-coated manganese dioxide (MnO2) nanoparticles loaded with parathyroid hormone (PMPC/Gelatin). The characteristics of these scaffolds were meticulously evaluated and confirmed the high sensitivity to H+, responsive drug release and ROS elimination. In vitro antibacterial analysis underscored the remarkable ability of PMPC/Gelatin scaffolds to substantially suppressed bacterial proliferation and colony formation. Furthermore, this nontoxic material demonstrated efficacy in mitigating ROS levels, thereby fostering osteogenic differentiation of bone marrow mesenchymal stem cells and enhancing angiogenic ability. Subsequently, the infected models of bone defects in rat skulls were established to investigate the effects of composite scaffolds on anti-bacteria and bone formation in vivo. The PMPC/Gelatin treatment exhibited excellent antibacterial activity, coupled with enhanced vascularization and osteogenesis at the defect sites. These compelling findings affirm that the PMPC/Gelatin composite scaffold represents a promising avenue for anti-bacteria and bone regeneration.

Autophagic inhibitor ROC-325 ameliorates glomerulosclerosis and podocyte injury via inhibiting autophagic flux in experimental FSGS mice.

BACKGROUND: Autophagy plays an important role in the pathogenesis of focal segmental glomerulosclerosis (FSGS). Podocyte-specific Yes-associated protein (YAP) deletion mice, referred to as YAP-KO mice, is considered a new animal model to study the underlying mechanism of FSGS. ROC-325 is a novel small-molecule lysosomal autophagy inhibitor that is more effective than chloroquine (CQ) and hydroxychloroquine (HCQ) in suppressing autophagy. In this study, we sought to determine the therapeutic benefit and mechanism of action of ROC-325 in YAP-KO mice, an experimental FSGS model. METHODS AND RESULTS: YAP-KO mice were treated with ROC-325 (50 mg/kg, p.o.) daily for one month. Our results revealed that albuminuria, mesangial matrix expension, and focal segmental glomerulosclerosis in YAP-KO mice were significantly attenuated by ROC-325 administration. Transmission electron microscopy and immunofluorescence staining showed that ROC-325 treatment significantly inhibited YAP-KO-induced autophagy activation by decreasing autophagosome-lysosome fusion and increasing LC3A/B and p62/SQSTM. Meanwhile, Immunofluorescence staining revealed that preapplication of ROC-325 in podocyte with YAP-targeted siRNA and mRFP-GFP-LC3 adenovirus markedly suppressed autophagic flux in vitro, suggesting that autophagy intervention may serve as a target for FSGS. CONCLUSIONS: These results showed that the role of autophagic activity in FSGS mice model and ROC-325 could be a novel and promising agent for the treatment of FSGS.

Exploring the interplay of parenting styles, basic empathy, domestic violence, and bystander behavior in adolescent school bullying: a moderated mediation analysis.

Introduction: This study investigates how parental styles, basic empathy, and family violence influence adolescents' bystander behaviors in school bullying. Methods: A survey was conducted with 1,067 students from three middle schools in southern China. Multifactor logistic regression and a moderated mediation model were employed to analyze the relationships between positive and negative parental styles, basic empathy, and bystander behaviors. Results: The study found significant correlations and predictive relationships: Positive parental styles were strongly associated with increased basic empathy (r = 0.29, p < 0.01) and behaviors that protect victims (r = 0.29, p < 0.01). In contrast, negative parental styles correlated positively with behaviors that support bullying (r = 0.12, p < 0.01) and instances of family violence (r = 0.62, p < 0.01). Basic empathy negatively predicted behaviors that promote bullying (ß = -0.098, p < 0.01) and positively predicted protective behaviors toward victims (ß = 0.249, p < 0.001). Furthermore, family violence weakened the positive effects of positive parental styles on both empathy (ß = -0.075, p < 0.001) and protective behaviors (ß = -0.025, p < 0.01). Conclusion: The findings indicate that positive parental styles indirectly promote adolescents' victim protector behaviors by enhancing their basic empathy, underscoring the importance of emotional cultivation. Meanwhile, family violence weakens the positive impact of these parental styles on basic empathy and protective behaviors, harming adolescents' emotional security and behavioral norms.

The biomechanical evaluation of metacarpal fractures fixation methods during finger movements: a finite element study.

Objective: This study used finite element analysis to simulate four commonly used fixation methods for metacarpal shaft oblique fractures during finger motion and evaluate their biomechanical performance. The aim was to provide evidence for clinically selecting the optimal fixation method, guiding early rehabilitation treatment, and reducing the risk of complications. Methods: Finite element analysis simulated dynamic proximal phalanx motion (60° flexion, 20° extension, 20° adduction, and 20° abduction). We analysed stress, displacement, and distributions for dorsal plates, intramedullary nails, Kirschner wire, and screw fixation methods. Results: At 60° of finger flexion and 20° of abduction, plate fixation demonstrated greater stability and minimal displacement, with a peak displacement of 0.19 mm; however, it showed higher stress levels in all motion states, increasing the risk of failure. The stability of the intramedullary nail was similar to that of the dorsal plate, with a maximum displacement difference of 0.04 mm, and it performed better than the dorsal plate during adduction of 20°. Kirschner wire showed the highest stress levels of 81.6 Mpa during finger flexion of 60°, indicating a greater risk of failure and unstable displacement. Screws had lower stress levels in all finger motion states, reducing the risk of failure, but had poorer stability. Stress and displacement distributions showed that the dorsal plate, intramedullary nail, and Kirschner wire mainly bore stress on the implants, concentrating near the fracture line and the proximal metacarpal. In contrast, the screws partially bore stress in the screw group. The anterior end of the metacarpal mainly hosted the maximum displacement. Conclusion: This study demonstrates that under simulated finger motion states, the dorsal plate fixation method provides the best stability in most cases, especially during finger flexion and abduction. However, high stress levels also indicate a higher risk of failure. The intramedullary nail is similar to the dorsal plate in stability and performs better in certain motion states. Kirschner wire exhibits the highest risk of failure during flexion. Although screws have poorer stability in some motion states, they offer a lower risk of failure. These findings provide important reference and surgical selection strategies for treating metacarpal fractures.

Photodynamic hemostatic silk fibroin film with photo-controllable modulation of macrophages for bacteria-infected wound healing.

Massive hemorrhage and chronic wounds caused by bacterial infections after trauma are significant challenges in clinical practice. An ideal hemostatic wound dressing should simultaneously manage bleeding and prevent bacterial infections and also hold excellent biocompatibility and bioactivities to successfully modulate immune microenvironments to promote wound healing. In this study, a silk fibroin-based light-responsive film was demonstrated to possess effective capacity of light-induced non-compressible hemostasis on liver hemorrhage and tail bleeding in vivo by binding with blood platelets to promote the clotting cascade. The blood loss of the rats was significantly less after C-MASiF films were applied, which were 1223.33 ± 347.9 mg (liver trauma) and 363.33 ± 60.28 mg (tail trimming). Importantly, the films exhibited photo-controllable modulation activity on macrophages through repeated near-infrared irradiation to regulate the immune microenvironment to enhance photodynamic antibacterial therapy. Moreover, the light-responsive silk fibroin film effectively promoted Staphylococcus aureus infected burn wound healing in vivo. The quantity of residual bacteria in the wound sites of mice in the C-MASiF films group (0.05 ± 0.0047 × 108 CFU mL-1) was considerably less than that in the control group (3.18 ± 0.75 × 108 CFU mL-1), and the wound area in the C-MASiF group (78.03% ± 4.12%) was considerably smaller than that in the control group (60.33% ± 8.81%) after 14 days. Overall, this light-responsive silk fibroin film can provide a powerful strategy for wound healing of burns.

International operations and corporate R&D investment: Evidence from China.

This paper presents an examination of the relationship between international operations and corporate R&D investment. Using a large sample of Chinese listed firms for the 2009-2022 period and the ordinary least squares method, we find that international operations have a positive effect on corporate R&D investment. The finding remains valid after a battery of robustness tests. Mechanism tests show that international operations increase corporate R&D investment by diversifying product demand instead of increasing firms' international knowledge acquisition. This paper provides new evidence on the role of international operations in innovation activities.

The spatiotemporal analysis of SARS-CoV-2 transmission in China since the termination of the dynamic zero-COVID policy.

China's dynamic zero-COVID policy has effectively curbed the spread of SARS-CoV-2, while inadvertently creating immunity gaps within its population. Subsequent surges in COVID-19 cases linked to various SARS-CoV-2 lineages post-policy termination necessitate a thorough investigation into the epidemiological landscape. This study addresses this issue by analyzing a comprehensive dataset of 39,456 high-quality genomes collected nationwide over an 11-month period since policy termination. Through lineage assignment, phylogenetic analysis, pandemic pattern comparison, phylodynamic reconstruction, and recombination detection, we found that China's post-epidemic period could be divided into three stages, along with dynamic changes in dominant lineages. Geographical clustering of similar lineages implies the importance of cross-border cooperation among neighboring regions. Compared to the USA, UK, and Japan, China exhibits unique trajectories of lineage epidemics, characterized by initial lagging followed by subsequent advancement, indicating the potential influence of diverse prevention and control policies on lineage epidemic patterns. Hong Kong, Shanghai, and Hubei emerge as pivotal nodes in the nationwide spread, marking a shift in the transmission center from east to central regions of China. Although China hasn't experienced significant variant emergence, the detection and validation of the novel recombination event, XCN lineage, underscore the ongoing virus evolution. Overall, this study systematically analyzes the spatiotemporal transmission of SARS-CoV-2 virus in China since the termination of the dynamic zero-COVID policy, offering valuable insights for regional surveillance and evidence-based public health policymaking.

Neuromuscular Control Strategies in Basketball Shooting: Distance-Dependent Analysis of Muscle Synergies.

Basketball victory relies on an athlete's skill to make precise shots at different distances. While extensive research has explored the kinematics and dynamics of different shooting distances, the specific neuromuscular control strategies involved remain elusive. This study aimed to compare the differences in muscle synergies during basketball shooting at different distances, offering insights into neuromuscular control strategies and guiding athletes' training. Ten skilled shooting right-handed male basketball players participated as subjects in this experiment. Electromyographic (EMG) data for full-phase shooting were acquired at short (3.2 m), middle (5.0 m), and long (6.8 m) distances. Non-negative matrix decomposition extracted muscle synergies (motor modules and motor primitives) during shooting. The results of this study show that all three distance shooting can be broken down into three synergies and that there were differences in the synergies between short and long distances, with differences in motor primitive 1 and motor primitive 2 at the phase of 45% - 59% (p < 0.001, t* = 4.418), and 78% - 88% (p < 0.01, t* = 4.579), respectively, and differences in the motor module 3 found in the differences in muscle weights for rectus femoris (RF) (p = 0.001, d = -2.094), and gastrocnemius lateral (GL) (p = 0.001, d = -2.083). Shooting distance doesn't affect the number of muscle synergies in basketball shooting but alters synergy patterns. During long distance shooting training, basketball players should place more emphasis on the timing and synergistic activation of upper and lower limbs, as well as core muscles.

Global, regional and national trends in the burden of low bone mineral density from 1990 to 2030: A Bayesian age-period-cohort modeling study.

Low bone mineral density (LBMD) remains a global public health concern. To provide deeper insights, we retrieved and calibrated LBMD death and Disability-Adjusted Life Years (DALYs) data from the Global Burden of Disease 2021 (GBD 2021) database. We calculated the age-standardized rate (ASR) and estimated annual percentage change (EAPC) to delineate LBMD trends across sexes, age groups, Sociodemographic Index (SDI) regions, and countries. Spearman rank order correlation analysis was used to explore the relationship between SDI and ASR. Additionally, we constructed Bayesian age-period-cohort (BAPC) models to predict future trends in LBMD up to 2030, with the mean absolute percentage error (MAPE) used to evaluate prediction accuracy. Our analyses revealed that global deaths related to LBMD nearly doubled, from 250,930 in 1990 to 463,010 in 2021, and are projected to rise to 473,690 by 2030. However, the ASR exhibited an opposite trend, decreasing from 17.91 per 100,000 in 1990 to 15.77 per 100,000 in 2021, and is expected to further decline to 13.64 per 100,000 by 2030. The EAPC indicated descending trends in 1990-2021 and 2022-2030. Trends in LBMD varied across different subgroups by sex, age, and location. Males are projected to continue experiencing higher death numbers than females, though the gap is narrowing. The 90 to 94 age group consistently had the highest ASR from 1990 to 2030. Lower SDI remains a critical factor contributing to the higher burden of LBMD. Spearman rank order correlation analysis showed a negative correlation between SDI and ASR. We categorized 6 distinct trends in ASR across different countries, with most expected to experience a decline by 2030. The MAPE value (0.038 < 0.1) indicated that the BAPC model produced reliable predictions even under the COVID-19 pandemic.

Single­cell RNA sequencing analysis of human embryos from the late Carnegie to fetal development.

BACKGROUND: The cell development atlas of transition stage from late Carnegie to fetal development (7-9 weeks) remain unclear. It can be seen that the early period of human embryos (7-9 weeks) is a critical research gap. Therefore, we employed single­cell RNA sequencing to identify cell types and elucidate differentiation relationships. RESULTS: The single­cell RNA sequencing analysis determines eighteen cell clusters in human embryos during the 7-9 weeks period. We uncover two distinct pathways of cellular development and differentiation. Initially, mesenchymal progenitor cells differentiated into osteoblast progenitor cells and neural stem cells, respectively. Neural stem cells further differentiated into neurons. Alternatively, multipotential stem cells differentiated into adipocyte, hematopoietic stem cells and neutrophil, respectively. Additionally, COL1A2-(ITGA1 + ITGB1) mediated the cell communication between mesenchymal progenitor cells and osteoblast progenitor cells. NCAM1-FGFR1 facilitated the cell communication between mesenchymal progenitor cells and neural stem cells. Notably, NCAM1-NCAM1 as a major contributor mediated the cell communication between neural stem cells and neurons. Moreover, CGA-FSHR simultaneously mediated the communication between multipotential stem cells, adipocyte, hematopoietic stem cells and neutrophil. Distinct cell clusters activated specific transcription factors such as HIC1, LMX1B, TWIST1, and et al., which were responsible for their specific functions. These coregulators, such as HOXB13, VSX2, PAX5, and et al., may mediate cell development and differentiation in human embryos. CONCLUSIONS: We provide the cell development atlas for human embryos (7-9 weeks). Two distinct cell development and differentiation pathways are revealed.

Neural Encoding for Spatial Release from Informational Masking and its Correlation with Behavioral Metrics.

The central auditory system encompasses two primary functions: identification and localization. Spatial release from masking (SRM) highlights speech recognition in competing noise and improves the listening experience when a spatial cue is introduced between noise and target speech. This assessment focuses on the integrity of auditory function and holds clinical significance. However, infants or pre-lingual subjects sometimes provide less reliable results. This study investigates the value of cortical auditory evoked potentials (CAEPs) onset and acoustic change complex (ACC) as an objective measurement of SRM. Thirty normal-hearing young adults (11 males) were recruited. We found the spatial separation of signals and noise (±90 degrees symmetrically) resulted in a signal-to-noise ratio (SNR) improvement of 9.00 ± 1.71 dB behaviorally. It significantly enhanced cortical processing at all SNR levels, shortened CAEPs latencies, and increased amplitudes, resulting in a greater number of measurable peaks for ACC. SRM showed mild to moderate correlations with the differences between the two conditions in CAEP measures. The regression model combining N1'-P2' amplitude at 5 dB SNR (R2 = 0.26), P1 amplitude at 0 dB SNR (R2 = 0.14), and P1 latency at -5 dB SNR (R2 = 0.15), explained 45.3% of the variance in SRM. Our study demonstrates that introducing spatial cues can improve speech perception and enhance central auditory processing in normal-hearing young adults. CAEPs may contribute to predictions about SRM and hold potential for practical application.

The acoustic change complex evoked by location-change sounds in the elderly.

OBJECTIVE: We have shown that the acoustic change complex (ACC) can be elicited by changing the horizontal sound location in young individuals. In this study, we aimed to evaluate the application of ACC within the elderly and its relationship with behavioural results. DESIGN: The minimum audible angle (MAA), as well as onset cortical auditory evoked potentials (onset-CAEPs) and ACC elicited by the stimuli of location-change white noise (±45 to ±2 degrees) were recorded. Latencies and amplitudes were analysed using repeated-measures ANOVA. Pearson correlation analysis was conducted to examine the relationship between ACC and MAA. STUDY SAMPLE: Ten older adults with normal hearing (NH) and twenty with presbycusis. RESULTS: The ACC was effectively elicited with angular variations in elderly participants. The onset-CAEP N1 latency, ACC N1'-P2' amplitude, and N1' latency were all associated with the angle shifts, with the N1' latency being the most predictive factor for angle discrimination. The consistency between MAA and ACC made them complementary for the clinical evaluation of sound localisation. CONCLUSIONS: The utilisation of ACC, evoked by location-change sounds, presented a promising clinical objective measure for evaluating sound localisation abilities in the elderly.

Role of Microglial Mitophagy in Alleviating Postoperative Cognitive Dysfunction: a Mechanistic Study.

Postoperative cognitive dysfunction (POCD), a common complication following anesthesia and surgery, is influenced by hippocampal neuroinflammation and microglial activation. Mitophagy, a process regulating inflammatory responses by limiting the accumulation of damaged mitochondria, plays a significant role. This study aimed to determine whether regulating microglial mitophagy and the cGAS-STING pathway could alleviate cognitive decline after surgery. Exploratory laparotomy was performed to establish a POCD model using mice. Western blotting, immunofluorescence staining, transmission electron microscopy, and mt-Keima assays were used to examine microglial mitophagy and the cGAS-STING pathway. Quantitative polymerase chain reaction (qPCR) was used to detect inflammatory mediators and cytosolic mitochondrial DNA (mtDNA) levels in BV2 cells. Exploratory laparotomy triggered mitophagy and enhanced the cGAS-STING pathway in mice hippocampi. Pharmacological treatment reduced microglial activation, neuroinflammation, and cognitive impairment after surgery. Mitophagy suppressed the cGAS-STING pathway in mice hippocampi. In vitro, microglia-induced inflammation was mediated by mitophagy and the cGAS-STING pathway. Small interfering RNA (siRNA) of PINK1 hindered mitophagy activation and facilitated the cytosolic release of mtDNA, resulting in the initiation of the cGAS-STING pathway and innate immune response. Microglial mitophagy inhibited inflammatory responses via the mtDNA-cGAS-STING pathway inducing microglial mitophagy and inhibiting the mtDNA-cGAS-STING pathway may be an effective therapeutic approach for patients with POCD.

Preserving the Immune-Privileged Niche of the Nucleus Pulposus: Safeguarding Intervertebral Discs from Degeneration after Discectomy with Synthetic Mucin Hydrogel Injection.

Intervertebral disc (IVD) herniation is a prevalent spinal disorder, often necessitating surgical intervention such as microdiscectomy for symptomatic relief and nerve decompression. IVDs comprise a gel-like nucleus pulposus (NP) encased by an annulus fibrosus (AF), and their avascular nature renders them immune-privileged. Microdiscectomy exposes the residual NP to the immune system, precipitating an immune cell infiltration and attack that exacerbates IVD degeneration. While many efforts in the tissue engineering field are directed toward IVD regeneration, the inherently limited regenerative capacity due to the avascular and low-cellularity nature of the disc and the challenging mechanical environment of the spine often impedes success. This study, aiming to prevent IVD degeneration post-microdiscectomy, utilizes mucin-derived gels (Muc-gels) that form a gel at the surgical site, inspired by the natural mucin coating on living organisms to evade immune reorganization. It is shown that type I macrophages are present in severely degenerated human discs. Encapsulating IVDs within Muc-gels prevents fibrous encapsulation and macrophage infiltration in a mouse subcutaneous model. The injection of Muc-gels prevents IVD degeneration in a rat tail IVD degeneration model up to 24 weeks post-operation. Mechanistic investigations indicate that Muc-gels attenuate immune cell infiltration into NPs, offering durable protection against immune attack post-microdiscectomy.

Isolation, Purification of Phenolic Glycoside 1 from Moringa oleifera Seeds and Formulation of Its Liposome Delivery System.

In this study, N, N '-bis {4- [(α-L- rhamnosyloxy) benzyl]} thiourea (PG-1), a phenolic glycoside compound was purified from Moringa seed. The PG-1 has attracted extensive attention due to its anti-cancer, antioxidant, anti-inflammatory and hypoglycemic properties. However, some of its physicochemical properties such as oral bioavailability has not been studied. Herein, a highly purified PG-1 was extracted and incorporated in multiple layered liposomes (PG-1-L) to avoid its burst release and enhance oral bioavailability. After appropriate characterization, it was discovered that the obtained PG-1-L was stable, homogeneous and well dispersed with the average particle size being 89.26 ± 0.23 nm. Importantly, the in vitro release and in vivo oral bioavailability of PG-1-L were significantly improved compared with PG-1. In addition, MTT results showed that compared with the free PG-1, PG-1-L displayed obvious inhibitory effect on the HepG2 cells, while the inhibitory effect on healthy non-malignant 3T6 and LO-2 cells was not significant, indicating that PG-1-L had high safety. In conclusion, PG-1-L can be used as a promising delivery system and an ideal novel approach to improve the oral bioavailability and anticancer activity of PG-1.

POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo. Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p, and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p, miR-29a-3p, PIK3R1, and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1, PIK3R1, and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS: The POU2F1-miR-29b-3p/miR-29a-3p-PIK3R1/PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.

Global and regional prevalence and cardiovascular risk of primary aldosteronism: a systematic review and meta-analysis.

BACKGROUND: An updated understanding of global prevalence of primary aldosteronism (PA) is essential for the development of primary prevention and management strategies for PA. We aimed to provide update global and regional prevalence of PA and to evaluate cardiovascular risk of PA compared to essential hypertension (EH). METHODS: We systematically searched PubMed, Web of Science, and Embase for studies on the prevalence of PA or cardiovascular risk of PA published up to July 31, 2022 for this meta-analysis. Global prevalence of PA was calculated using random-effects inverse-variance models and cardiovascular risk of PA was estimated using random-effects models. RESULTS: We identified 39 articles for meta-analysis of PA prevalence, and 13 articles were included in the meta-analysis of cardiovascular risk. Global prevalence of PA was 9.4% (95% CI: 8.3-10.5), with a higher prevalence in males than in females. Prevalence of PA was higher in the South-East Asia than in other regions, and higher in lower middle-income countries than in other economic levels, with greater country-specific differences. Compared with EH, PA had an increased risk of coronary artery disease (OR=1.88, 95% CI: 1.41-2.50), stroke (OR=2.50, 95% CI: 2.08-3.02), heart failure (OR=2.06, 95% CI: 1.33-3.19), and atrial fibrillation (OR=3.17, 95% CI: 2.09-4.80). CONCLUSION: The management of the increasing number of patients with PA and its associated burden of cardiovascular disease is likely to place increasing pressure on health systems. Early detection of PA is essential to reduce the associated burden, especially in areas where the assessment of PA has not received sufficient attention.

Low Testosterone and High Leptin Activate PPAR Signaling to Induce Adipogenesis and Promote Fat Deposition in Caponized Ganders.

Low or insufficient testosterone levels caused by caponization promote fat deposition in animals. However, the molecular mechanism of fat deposition in caponized animals remains unclear. This study aimed to investigate the metabolomics and transcriptomic profiles of adipose tissues and study the effect of testosterone and leptin on the proliferation of adipocytes. We observed a significant enlargement in the areas of adipocytes in the abdominal fat tissues in capon, as well as increased luciferase activity of the serum leptin and a sharp decrease in the serum testosterone in caponized gander. Metabolomics and transcriptomic results revealed differentially expressed genes and differentially expressed metabolites with enhanced PARR signal pathway. The mRNA levels of peroxisome proliferators-activated receptor γ, fatty acid synthase, and suppressor of cytokine signaling 3 in goose primary pre-adipocytes were significantly upregulated with high leptin treatment and decreased significantly with increasing testosterone dose. Hence, reduced testosterone and increased leptin levels after caponization possibly promoted adipocytes proliferation and abdominal fat deposition by altering the expression of PPAR pathway related genes in caponized ganders. This study provides a new direction for the mechanism through which testosterone regulates the biological function of leptin and fat deposition in male animals.

Effectiveness of Cognitive-Based Interventions on Psychological Distress in Adolescents With Physical Disabilities: A Systematic Review and Meta-Analysis.

Adolescents with physical disabilities experience common psychological distress that interacts with impaired physical function. While cognitive-based interventions have been implemented for adolescents with physical disabilities, their effects on enhancing psychological health remain uncertain. This systematic review aimed to synthesise the effects of cognitive-based interventions on the psychological distress of this population and identify optimal components for evidence-based interventions. Following the PRISMA guideline, nine databases were searched to identify eligible randomised controlled trials examining the effects of cognitive-based interventions for adolescents with physical disabilities from inception to October 2023. Data syntheses were performed using the R software, employing random-effects models. Twelve trials involving 1201 participants were identified. The pooled results revealed that cognitive-based interventions did not yield noticeable effects in reducing anxiety (g = -0.43 for postintervention; -0.14 for medium term; -0.37 for long term), depression (g = -0.05 for postintervention; -0.02 for medium term; -0.15 for long term) and stress levels (g = -0.15) over time. The secondary outcome (physical function) improved significantly in the long term compared to the control groups (g = 0.31). Furthermore, this review identified variations in the effectiveness of CBIs among different recipients, durations and modes of delivery. Given the limited number and overall low quality of identified studies for each outcome, conducting high-quality randomised controlled trials is recommended to validate the effectiveness of cognitive-based interventions in reducing psychological distress among adolescents with physical disabilities.