Neuroprotection and mechanisms of ginsenosides in nervous system diseases: Progress and perspectives.

Ginsenosides are the primary component discernible from ginseng, including Rb1, Rb2, Rd, Rg1, Rg2, and compound K, and so forth. They have been shown to have multiple pharmacological activities. In recent years, more and more studies have been devoted to the neuroprotection of various ginsenosides against neurological diseases and their potential mechanisms. This paper comprehensively summarizes and reviews the neuroprotective effects of various ginsenosides on neurological diseases, especially acute and chronic neurodegenerative diseases, and their mechanisms, as well as their potential therapeutic applications to promote neuroprotection in disease prevention, treatment, and prognosis. Briefly, ginsenosides exert effective neuroprotective effects on neurological conditions, including stroke, Alzheimer's disease, Parkinson's disease, and brain/spinal cord injuries through a variety of molecular mechanisms, including anti-inflammatory, antioxidant, and anti-apoptotic. Among them, some signaling pathways play important roles in related processes, such as PI3K/Akt, TLR4/NF-κB, ROS/TXNIP/NLRP3, HO-1/Nrf2, Wnt/ß-catenin, and Ca2+ pathway. In conclusion, the present study reviews the research progress on the neuroprotective effects of ginsenosides in the last decade, with the aim of furnishing essential theoretical underpinning and effective references for further research and exploration of the multiple medicinal values of Chinese herbal medicines and their small molecule compounds, including ginseng and panax ginseng. Because there is less evidence in the existing clinical studies, future research should be focused on clinical trials in order to truly reflect the clinical value of various ginsenosides for the benefit of patients.

Abnormal circulating steroids refine risk of progression to heart failure in ischemic heart disease.

BACKGROUND: Patients with ischemic heart disease (IHD) experience a high incidence of progression to heart failure (HF) despite current therapies. We speculated that steroid hormone metabolic disorders distinct adverse phenotypes and contribute to HF. METHODS: We measured 18 steroids using liquid chromatography with tandem mass spectrometry in 2023 patients from the Registry Study of Biomarkers in Ischemic Heart Disease (BIOMS-IHD), including 1091 patients with IHD in a retrospective discovery set and 932 patients with IHD in a multicentre validation set. Our outcomes included incident HF after a median follow-up of 4 years. RESULTS: We demonstrated steroid-based signatures of inflammation, coronary microvascular dysfunction and left ventricular hypertrophy that were associated with subsequent HF events in patients with IHD. In both cohorts, patients with a high steroid-heart failure score (SHFS) (>1) exhibited a greater risk of incident HF than patients with a low SHFS (≤1). The SHFS further improved the prognostic accuracy beyond clinical variables (net reclassification improvement of 0.628 in the discovery set and 0.299 in the validation set) and demonstrated the maximal effect of steroid signatures in patients with IHD who had lower B-type natriuretic peptide levels (pinteraction = 0.038). CONCLUSIONS: A steroid-based strategy can simply and effectively identify individuals at higher HF risk who may derive benefit from more intensive follow-ups.

Epigenetic regulation in the commitment of progenitor cells during retinal development and regeneration.

Retinal development is initiated by multipotent retinal progenitor cells, which undergo several rounds of cell divisions and subsequently terminal differentiation. Retinal regeneration is usually considered as the recapitulation of retinal development, which share common mechanisms underlying the cell cycle re-entry of adult retinal stem cells and the differentiation of retinal neurons. However, how proliferative retinal progenitor cells perform a precise transition to postmitotic retinal cell types during the process of development and regeneration remains elusive. It is proposed that both the intrinsic and extrinsic programming are involved in the transcriptional regulation of the spatio-temporal fate commitment. Epigenetic modifications and the regulatory mechanisms at both DNA and chromatin levels are also postulated to play an important role in the timing of differentiation of specific retinal cells. In the present review, we have summarized recent knowledge of epigenetic regulation that underlies the commitment of retinal progenitor cells in the settings of retinal development and regeneration.

Meta-analysis of efficacy and safety of pembrolizumab for the treatment of advanced or recurrent cervical cancer.

BACKGROUND: This meta-analysis seeks to assess the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. METHODS: Databases from PubMed, Embase, and the Cochrane Library were all thoroughly searched for pertinent research. Outcomes include complete response (CR), partial response (PR), stable disease (SD), disease progression (PD), overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) were retrieved for further analysis. RESULTS: Ten trials with 721 patients were included in this meta-analysis. The pooled results for patients with cervical cancer receiving pembrolizumab were as follows: CR (0.06, 95%CI: 0.02-0.10), PR (0.15, 95%CI: 0.08-0.22), SD (0.16, 95%CI: 0.13-0.20), PD (0.50, 95%CI: 0.25-0.75), ORR (0.26, 95%CI: 0.11-0.41) and DCR (0.42, 95%CI: 0.13-0.71), respectively. Regarding survival analysis, the pooled mPFS and mOS were 3.81 and 10.15 months. Subgroup analysis showed that pembrolizumab in combination was more beneficial in CR (0.16 vs. 0.03, p = 0.012), PR (0.24 vs. 0.08, p = 0.032), SD (0.11 vs. 0.19, p = 0.043), ORR (0.42 vs. 0.11, p = 0.014), and mPFS (5.54 months vs. 2.27 months, p < 0.001) than as single agent. The three most common AEs were diarrhoea (0.25), anaemia (0.25), and nausea (0.21), and the incidence of grade 3-5 AEs was significantly lower, rarely surpassing 0.10. CONCLUSIONS: For patients with advanced or recurrent cervical cancer, this systematic review and meta-analysis demonstrated that pembrolizumab had a favourable efficacy and tolerability. Future research will primarily focus on optimising customised regiments that optimally integrate pembrolizumab into new therapies and combination strategies. Designed to maximise patient benefit and efficiently control adverse effects while maintaining a high standard of living.

This study demonstrated the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. The study found that an upfront combination of chemotherapy and pembrolizumab immunotherapy appears to be a compelling strategy for these patients. More large-scale and multicentre randomised controlled trials will be required in the future to validate the precise benefits of pembrolizumab in new therapies and combination strategies for the treatment of cervical cancer.

Bioinformatics analysis of the prognosis and biological significance of HMGB1, HMGB2, and HMGB3 in gastric cancer.

High mobility group box (HMGB) consists primarily of HMGB1, HMGB2, and HMGB3 proteins. Although abnormal HMGB expression is associated with various tumors, the relationship with gastric cancer (GC) remains unclear. In this study, HMGB1, HMGB2, and HMGB3 expression was analyzed using the Oncomine and TCGA databases. Correlations between HMGB1, HMGB2, and HMGB3 and clinicopathological factors were analyzed. cBioPortal was used to analyze HMGB1, HMGB2, and HMGB3 genetic alterations and its gene regulation network in GC tissue. HMGB1, HMGB2, and HMGB3 expression was higher in tumor tissues than in normal tissues, especially in GC. High HMGB1, HMGB2, and HMGB3 expression may predict a poor prognosis among patients with GC (hazard ratios [HR] = 1.90; 95% confidence interval [CI]: [1.30-2.78]) and human digestive system neoplasm (HR = 1.85; 95% CI [1.64-2.10]). These findings suggest that HMGB1, HMGB2, and HMGB3 may be useful prognostic indicators for patients with GC.

Improving the Resolution and Accuracy of Groundwater Level Anomalies Using the Machine Learning-Based Fusion Model in the North China Plain.

The launch of GRACE satellites has provided a new avenue for studying the terrestrial water storage anomalies (TWSA) with unprecedented accuracy. However, the coarse spatial resolution greatly limits its application in hydrology researches on local scales. To overcome this limitation, this study develops a machine learning-based fusion model to obtain high-resolution (0.25°) groundwater level anomalies (GWLA) by integrating GRACE observations in the North China Plain. Specifically, the fusion model consists of three modules, namely the downscaling module, the data fusion module, and the prediction module, respectively. In terms of the downscaling module, the GRACE-Noah model outperforms traditional data-driven models (multiple linear regression and gradient boosting decision tree (GBDT)) with the correlation coefficient (CC) values from 0.24 to 0.78. With respect to the data fusion module, the groundwater level from 12 monitoring wells is incorporated with climate variables (precipitation, runoff, and evapotranspiration) using the GBDT algorithm, achieving satisfactory performance (mean values: CC: 0.97, RMSE: 1.10 m, and MAE: 0.87 m). By merging the downscaled TWSA and fused groundwater level based on the GBDT algorithm, the prediction module can predict the water level in specified pixels. The predicted groundwater level is validated against 6 in-situ groundwater level data sets in the study area. Compare to the downscaling module, there is a significant improvement in terms of CC metrics, on average, from 0.43 to 0.71. This study provides a feasible and accurate fusion model for downscaling GRACE observations and predicting groundwater level with improved accuracy.

BOLD-fMRI reveals the association between renal oxygenation and functional connectivity in the aging brain.

Aging is accompanied by a decline in physical and cognitive function. Vascular aging may provide a major influence on these measures. The purpose of this study was to explore the relationship between renal oxygenation and functional connectivity of the aging brain because of the anatomic and hemodynamic similarities between cerebral and renal vessels. Fifty-two healthy older adults were recruited to undergo a BOLD-fMRI scan of the brain and kidneys, and forty-four healthy younger subjects were recruited as the control group. First, cerebral functional connectivity density (FCD) was used to evaluate functional connectivity. Renal medullary and cortical R2* values were extracted respectively, and the ratio of medullary and cortical R2* values (MCR) was calculated. Then, the association between brain FCD and renal MCR was analyzed. Compared with younger adults, the elderly group showed higher renal medullary R2* and MCR, which might reflect a slight abnormality of renal oxygenation with aging. The older subjects also showed enhanced FCD in bilateral motor-related regions and decreased FCD in regions of the default mode network (DMN). The findings indicated that the functional connectivity in the DMN and motor cortices was vulnerable to aging. Moreover, the altered brain FCD values in the watershed regions, DMN and motor cortices were significantly correlated with the renal MCR value in the elderly group. The association between renal oxygenation abnormalities and spontaneous activity in the brain might reflect vascular aging and its influence on the kidney and brain during aging to some extent. This study provided a new perspective for understanding the relationship between tissue oxygenation and brain functional connectivity.

Altered Dynamic Functional Network Connectivity in Frontal Lobe Epilepsy.

Frontal lobe epilepsy has recently been associated with disrupted brain functional connectivity; variations among various resting-state networks (RSNs) across time remains largely unclear. This study applied dynamic functional network connectivity (dFNC) analysis to investigate functional patterns in the temporal and spatial domains of various functional systems in FLE. Resting-state fMRI data were acquired from 19 FLE patients and 18 controls. Independent component analysis was used to decompose RSNs, which were grouped into seven functional systems. Sliding windows and clustering approach were used to identify the dFNC patterns. Then, state-specific connectivity pattern and dynamic functional state interactions (dFSIs) were evaluated. Compared with healthy controls, FLE patients exhibited decreased dFNC in almost all four patterns, changes that were mostly related to the frontoparietal system, suggesting a disturbed communication of the frontoparietal system with other systems in FLE. Additionally, regarding the fundamental connectivity pattern (state 3 in this study), FLE showed decreased time spent in this state. Moreover, the duration positively correlated with seizure onset. Furthermore, significantly reduced dynamic connections in this state were observed in the frontoparietal system linked to the cerebellar and subcortical systems. These findings imply abnormal fundamental dynamic interactions and dysconnectivity associated with the subcortical and cerebellar regulation of dysfunctions in frontoparietal regions in FLE. Finally, based on the developed FSI analysis, temporal dynamic abnormalities among states were observed in FLE. Therefore, this altered dynamic FNC extended our understanding of the abnormalities in the frontoparietal system in FLE. The dynamic FNC provided novel insight into the fundamental pathophysiological mechanisms in FLE.

Pretreatment Controlling Nutritional Status Score and Lactate Dehydrogenase as Predictive Markers of Survival in Patients with Malignant Peritoneal Mesothelioma.

OBJECTIVE: To investigate the relationships between the Controlling Nutritional Status (CONUT) score and ascites fluid lactate dehydrogenase (LDH) level, and prognosis in patients with malignant peritoneal mesothelioma (MPeM). METHODS: A total of 125 patients with MPeM were selected for the study using a pathological screening method. Once the diagnosis is established, before the treatment their clinical characteristics and nutritional evaluations were recorded including CONUT score and ascites LDH level. The associations between CONUT, ascites LDH, and other clinicopathological features including body mass index, asbestos exposure, pathological type, and treatment method were analyzed. Prognostic parameters predicting overall survival (OS) were analyzed by Cox regression. RESULTS: High CONUT score, high ascites LDH level were positively associated with poor prognosis in patients with MPeM according to univariate analyses (P < 0.001, P < 0.001, respectively), and CONUT score and ascites LDH were independent predictors of a poor prognosis according to multivariate analysis. When the CONUT score is greater than 3 and the ascites LHD is greater than 474 IU/l, it indicates a poor prognosis. CONCLUSIONS: CONUT score and ascites LDH are important factors influencing the prognosis of MPeM patients and should thus be considered in clinical applications.

Analysis of prognostic factors of patients with malignant peritoneal mesothelioma.

BACKGROUND: The study aims to find out independent prognostic factors for patients with malignant peritoneal mesothelioma (MPeM). METHODS: Patients with pathologically proven MPeM were retrospectively reviewed. Potential prognostic factors were analyzed, including age, gender, asbestos exposure, body mass index (BMI), treatment, and laboratory results, such as blood routine examination and liver functions. The influences of various risk factors on the prognoses were analyzed by univariate analysis. A Cox regression model analysis established independent factors for the survival prognosis of the patients. RESULTS: Seventy MPeM patients, including 33 patients who received intraperitoneal chemotherapy with cisplatin, 14 patients who received systemic chemotherapy with cisplatin + pemetrexed, and 21 untreated patients were included in this study. The 1-year survival was 32.9%, the 2-year survival was 10%, and the 3-year survival was 2.9%. The median age of MPeM was 62 years, and the female-to-male ratio was 1:0.56. The univariate and multivariate analyses showed that treatment, albumin (ALB), and blood neutrophil-to-lymphocyte ratio (NLR) were independent factors that affected the overall survival (OS) of MPeM patients. CONCLUSION: High blood NLR and hypoalbuminemia are adverse prognostic factors for MPeM patients. Systemic chemotherapy and intraperitoneal chemotherapy can prolong the survival period.

Therapeutic effects of hydrogen on chronic graft-versus-host disease.

The incidence of chronic graft-versus-host disease (cGVHD) is rising recent years, which has been the leading cause of non-transplantation mortality post allogenetic hematopoietic stem cell transplantation (HSCT). Imbalance of inflammatory cytokines and fibrosis plays critical roles in the pathogenesis of cGVHD. Recent studies showed that molecular hydrogen has anti-inflammatory, antioxidant, anti-fibrosis effects. Therefore, we hypothesized that molecular hydrogen may have therapeutic effects on cGVHD. To determine whether hydrogen could protect mice from cGVHD in an MHC-incompatible murine bone marrow transplantation (BMT) model, survival rates of mice were calculated, and skin lesions were also evaluated after BMT. This article demonstrated that administration of hydrogen-rich saline increased survival rate of cGVHD mice. Administration of hydrogen-rich saline after transplantation also reduced skin lesions of cGVHD mice. Previously, we reported the therapeutic effects of hydrogen on acute GVHD. However, there was no report on the therapeutic effects of hydrogen on cGVHD mice. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on cGVHD. This study will provide new ideas on the treatment of cGVHD and has important theoretical values.

Induction and activation of human Th17 by targeting antigens to dendritic cells via dectin-1.

Recent compelling evidence indicates that Th17 confer host immunity against a variety of microbes, including extracellular and intracellular pathogens. Therefore, understanding mechanisms for the induction and activation of Ag-specific Th17 is important for the rational design of vaccines against pathogens. To study this, we employed an in vitro system in which influenza hemagglutinin (HA) 1 was delivered to dendritic cells (DCs) via Dectin-1 using anti-human Dectin-1 (hDectin-1)-HA1 recombinant fusion proteins. We found that healthy individuals maintained broad ranges of HA1-specific memory Th17 that were efficiently activated by DCs targeted with anti-hDectin-1-HA1. Nonetheless, these DCs were not able to induce a significant level of HA1-specific Th17 responses even in the presence of the Th17-promoting cytokines IL-1ß and IL-6. We further found that the induction of surface IL-1R1 expression by signals via TCRs and common γ-chain receptors was essential for naive CD4(+) T cell differentiation into HA1-specific Th17. This process was dependent on MyD88, but not IL-1R-associated kinase 1/4. Thus, interruptions in STAT3 or MyD88 signaling led to substantially diminished HA1-specific Th17 induction. Taken together, the de novo generation of pathogen-specific human Th17 requires complex, but complementary, actions of multiple signals. Data from this study will help us design a new and effective vaccine strategy that can promote Th17-mediated immunity against microbial pathogens.

Resting State fMRI Demonstrates a Disturbance of the Cerebello-Cortical Circuit in Essential Tremor.

Individuals with essential tremor (ET) have postural and active movement abnormalities. Disturbances in the cerebello-thalamo-cortical circuit may contribute to the several motor symptoms of ET. Resting state fMRI provides a valuable, noninvasive tool to study intrinsic activation in the human brain, particularly in the brains of individuals with neuropsychiatric diseases. To investigate the low frequency oscillation features of intrinsic activation in ET in this study, we performed a resting state fMRI analysis in 24 patients with ET and 23 healthy controls. The amplitudes of low frequency fluctuation (ALFF) were analyzed. When compared with healthy controls, patients showed significantly enhanced ALFF in the bilateral cerebral cortex, which is related to motor function, including the pre- and post-central gyrus, supplementary motor area and paracentral lobule. The larger ALFF value in the right precentral gyrus is related to a longer duration of tremor. The decreased ALFF in the bilateral cerebellum was also observed in patients. In addition, aberrant ALFF in the right cerebellar tonsil was negatively associated with the duration of tremor. Our findings suggest that abnormalities exist in the intrinsic activation of brain regions in patients with ET. These findings provide noninvasive evidence that supports the hypothesis that the abnormality of intrinsic activity in the cerebello-cerebral cortex pathway could be associated with the motor-related symptoms of ET. Furthermore, the duration of a tremor might relate to the severity of the alterations to the motor system of ET.

CT differentiation of diffuse malignant peritoneal mesothelioma and peritoneal carcinomatosis.

BACKGROUND AND AIM: Diffuse malignant peritoneal mesothelioma (DMPM) and peritoneal carcinomatosis (PC) have similar imaging in computer tomography (CT). We aimed to distinguish them. METHODS: Computer tomography findings were evaluated in 48 DMPM and 47 PC for the peritoneal, mesenteric, omentum, lymph nodes, viscera infiltration, ascites and pleural plaques. RESULTS: Two groups had no difference in terms of thickness, clinical manifestation, diameter of lymph nodes, ascites, and viscera infiltration. But they showed differences in the following: Ratio of asbestos exposure in DMPM group was higher. Smooth and irregular peritoneal thickening were more seen in DMPM group; peritoneal nodules were more commonly detected in PC group. Forty-eight cases of peritoneum in DMPM showed mild enhanced, while 14 patients in PC showed severe enhanced. Nodular type of omentum was more common in PC group than in DMPM group; omental cake was more commonly detected in DMPM group. Mesentery involvement was more commonly seen in DMPM group. Location of enlarged lymph nodes in cardiophrenic region was more frequently identified in DMPM, whereas location of enlarged lymph nodes in retroperitoneal region was more frequently identified in PC. Lymph nodes fusion was more frequently visualized in PC. Fixation of the intestinal wall was more common in DMPM. Pleural plaque was more common in DMPM. PC had distant metastasis except primary foci and peritoneum. In PC, tumor origins were ovary in 10, digestive system in 21, breast in one. CONCLUSION: Using a combination of CT findings may increase our ability to distinguish PC from DMPM.

CT differentiation of malignant peritoneal mesothelioma and tuberculous peritonitis.

OBJECTIVE: The aim of this study was to determine which computed tomography (CT) findings were useful in differentiating malignant peritoneal mesothelioma (MPM) and tuberculous peritonitis (TBP). METHODS: CT scans performed in 53 patients with MPM and 27 patients with TBP confirmed by pathology were retrospectively reviewed. The CT findings were evaluated for the morphologic appearance of ascites, peritoneum, mesenterium and omentum involvement, enlarged lymph nodes, solid abdominal viscera infiltration and metastases, and thoracic changes. The Pearson χ (2) test was used to compare differences between groups. RESULTS: Patients in both groups displayed a high proportion of peritoneum and mesenterium thickening. However, there were no obvious differences observed for ascites or swollen lymph nodes. There were significant differences in the following aspects between the two groups: (1) smooth peritoneal thickening was more frequent in patients with TBP, while irregular thickening was more frequently observed in patients with MPM; (2) caked omentum stratification was more common in patients with MPM; (3) mesentery involvement was less commonly observed in patients with TBP; (4) abdominal viscera infiltration and pleural plaques were more common in patients with MPM (46/53 and 48/53, respectively) than in those with TBP (0/27 and 0/27); and (5) more patients in the TBP group (14/27) displayed pleural effusion, and extraperitoneal tuberculosis was more common in patients with TBP (20/27). CONCLUSION: Although most CT findings analyzed are observed in both diseases, each disease has its own several unique characteristics. Therefore, using a combination of CT findings may increase our ability to distinguish TBP from MPM.

The Clinical Efficacy of Platelet-Rich Plasma Injection Therapy versus Different Control Groups for Chronic Low Back Pain: A Network Meta-Analysis of Randomized Controlled Trials.

Objective: Low back pain is one of the main causes of disability in the world. Although regenerative medicine may represent breakthroughs in the management of low back pain, its use remains controversial. Therefore, we conducted a meta-analysis to evaluate the clinical efficacy of platelet-rich plasma (PRP) injection therapy versus different control groups for chronic low back pain during 4 weeks, 3 months, and 6 months. Methods: Different electronic databases were searched for randomized controlled trials up to August 2023. Mean changes from baseline in pain and Oswestry Disability Index (ODI) scores at 4 weeks, 3 months, and 6 months and standard deviations of outcome were recorded. Results: Four articles with 154 cases were finally included in this meta-analysis. After 4 weeks, corticosteroid (CS) was the optimal treatment option for chronic low back pain in terms of improvement in pain and disability index (surface under the cumulative ranking curve [SUCRA]=71.3%, SUCRA=57.8%, respectively). After 3 months, radiofrequency (RF) emerged as the best therapy in pain (SUCRA=100%) and disability index (SUCRA=98.5%), followed by PRP (SUCRA=62.3%, SUCRA=64.3%, respectively), CS (SUCRA=24.6%, SUCRA=25.9%, respectively) and lidocaine (SUCRA=13.1%, SUCRA=11.3%, respectively). At 6 months, RF was most likely to be the best treatment in pain (SUCRA=94.9%) and disability index (SUCRA=77.3%), followed by PRP (SUCRA=71.2%, SUCRA=79.6%, respectively). However, compared with the last follow-up, there was a slight downward trend in improvement pain and disability index with RF, while PRP was still an upward trend. Conclusion: This study demonstrated better short-term improvement of chronic low back pain with CS after 4 weeks. PRP and RF improvement effects matched, but follow-up of at least 6 months showed that PRP seemed to be more advantageous in improvement in disability indices. Considering the limitations of this study, these conclusions still need to be verified by more comparative RCTs and a longer follow-up period.

Hematopoietic Stem Cell Transplantation in the Management of Myelodysplastic Syndrome: A Retrospective, Current, and Future Perspective.

Myelodysplastic syndrome (MDS) is a clonal disorder that affects hematopoietic stem cells (HSCs), primarily occurring in the elderly population. Lower-risk MDS is characterized by a decrease in blood cells, whereas higher-risk MDS is associated with an increased risk of transformation to acute myeloid leukemia (AML). Currently, the treatment of MDS is still unsatisfactory, although demethylating agents, azacitidine (AZA), and decitabine (Dec) have been successfully used to treat MDS and improve survival rates. However, hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for MDS patients, effectively increasing patient survival and quality of life. Nevertheless, treatment-related toxicity, graft-versus-host disease, infectious complications, and relapse are still major post-transplant issues. In this review, through a retrospective analysis of past and present HSCT for the treatment of MDS, we provide insights for the future.

RNA-sequencing expression profile and functional analysis of retinal pigment epithelium in atrophic age-related macular degeneration.

The retinal pigment epithelium (RPE) is fundamental to sustaining retinal homeostasis. RPE abnormality leads to visual defects and blindness, including age-related macular degeneration (AMD). Although breakthroughs have been made in the treatment of neovascular AMD, effective intervention for atrophic AMD is largely absent. The inadequate knowledge of RPE pathology is hindered by a lack of patient RPE datasets, especially at the single-cell resolution. In this study, we delved into a large-scale single-cell resource of AMD donors in which RPE cells were occupied in a substantial proportion. Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD. Both in vivo and in vitro models revealed that carboxypeptidase X, M14 family member 2 (CPXM2) was specifically expressed in the RPE cells of atrophic AMD, which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells. Additionally, silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model. Thus, our results demonstrate that CPXM2 plays a crucial role in regulating atrophic AMD and may serve as a potential therapeutic target for atrophic AMD.

Three-dimensional finite element analysis of the biomechanical behaviour of different dental implants under immediate loading during three masticatory cycles.

The study aimed to evaluate the impact of varying modulus of elasticity (MOE) values of dental implants on the deformation and von Mises stress distribution in implant systems and peri-implant bone tissues under dynamic cyclic loading. The implant-bone interface was characterised as frictional contact, and the initial stress was induced using the interference fit method to effectively develop a finite element model for an immediately loaded implant-supported denture. Using the Ansys Workbench 2021 R2 software, an analysis was conducted to examine the deformation and von Mises stress experienced by the implant-supported dentures, peri-implant bone tissue, and implants under dynamic loading across three simulated masticatory cycles. These findings were subsequently evaluated through a comparative analysis. The suprastructures showed varying degrees of maximum deformation across zirconia (Zr), titanium (Ti), low-MOE-Ti, and polyetheretherketone (PEEK) implant systems, registering values of 103.1 µm, 125.68 µm, 169.52 µm, and 844.06 µm, respectively. The Zr implant system demonstrated the lowest values for both maximum deformation and von Mises stress (14.96 µm, 86.71 MPa) in cortical bone. As the MOE increased, the maximum deformation in cancellous bone decreased. The PEEK implant system exhibited the highest maximum von Mises stress (59.12 MPa), whereas the Ti implant system exhibited the lowest stress (22.48 MPa). Elevating the MOE resulted in reductions in both maximum deformation and maximum von Mises stress experienced by the implant. Based on this research, adjusting the MOE of the implant emerged as a viable approach to effectively modify the biomechanical characteristics of the implant system. The Zr implant system demonstrated the least maximum von Mises stress and deformation, presenting a more favourable quality for preserving the stability of the implant-bone interface under immediate loading.

Using GRACE to Detect Groundwater Variation in North China Plain after South-North Water Diversion.

The gravity recovery and climate experiment (GRACE) and its Follow-On mission provide a versatile tool for monitoring groundwater depletion in North China Plain (NCP). However, intermittent data gaps and inherent coarse spatial resolution have restricted the continuous detection of regional groundwater storage anomaly (GWSA) after 2014, the period of interest during the implementation of the south-to-north water diversion middle route project (SNWDP). Here, we investigated the spatiotemporal changes of GWSA in the NCP during 2004 to 2020 based on continuous downscaled GRACE data. First, we derived the continuous terrestrial water storage anomaly from six GRACE and Follow-On solutions (i.e., spherical harmonics (SH) and mass concentration [mascon] solutions). Second, we employed a long short-term memory (LSTM) model and water balance equation to downscale GWSA (i.e., 0.25° × 0.25°). Lastly, we investigated its spatiotemporal characteristics before (2004 to 2014) and after (2015 to 2020) the SNWDP operation. We show the applicability of the continuous downscaled GWSA to capture the characteristics of in situ measurements. The GWSA detects groundwater depletion at a significant (p < 0.05) rate of -17.09 ± 1.80 (SH) and -17.87 ± 1.65 (mascon) mm/a during 2004 to 2014, but a recovering trend of 7.18 ± 3.98 (SH) and 8.23 ± 4.99 (mascon) during 2015 to 2018. The subsequent groundwater extraction and precipitation reduction from 2019 to 2020, resulted in the decreasing trend of GWSA from 2015 to 2020, which is -19.11 ± 8.75 (SH) and -19.72 ± 9.08 mm/a (mascon), respectively. Spatially, the overall depletion trends become nonsignificant along the canals of SNWDP compared to the period 2004 to 2014, and groundwater recovering with trends <6 mm/a near Beijing and Tianjin are detected by the mascon solution during 2015 to 2020.