ATF1 promotes ferroptosis resistance in lung cancer through enhancing mRNA stability of PROM2.

BACKGROUND: Ferroptotic proteins are promising therapeutic targets for lung cancer. The PROM2 is upregulated in lung cancer and known to suppress ferroptosis. This study examined the molecular mechanisms for PROM2-induced ferroptosis resistance in lung cancer. METHODS: Ferroptosis in lung cancer was assessed by iron kit, and transmission electron microscopy was applied to observe the changes in mitochondrial morphology. BODIPY™ was applied to test the lipid ROS, and MeRIP was performed to test the m6A modification of PROM2. RIP assay was employed for confirming the binding between METTL3 and PROM2. In addition, dual luciferase assay was employed for exploring the transcriptional regulation of ATF1 to METTL3, and the binding relation between ATF1 and METTL3 promoter region was explored by ChIP assay. RESULTS: Expression levels of PROM2 were significantly higher in lung cancer cell lines than a noncancerous control line, and PROM2 knockdown significantly reduced both cancer cell viability and proliferation rate. In addition, PROM2 knockdown reduced xenograft tumor growth and exacerbated erastin-induced ferroptosis. Compared to PROM2 mRNA from control cells, transcripts in lung cancer cells exhibited enhanced m6A levels, and showed greater binding with METTL3. Further, ATF1 upregulated METTL3 transcription, thereby stabilizing PROM2 mRNA and increasing ferroptosis resistance. CONCLUSION: ATF1 could promote ferroptosis resistance in lung cancer through enhancing mRNA stability of PROM2. Thus, our work might shed novel insights on discovering therapeutic strategy for lung cancer.

Coastal conversion alters topsoil carbon, nitrogen and phosphorus stocks and stoichiometric balances in subtropical coastal wetlands.

The extensive conversion of coastal wetlands into agricultural and aquaculture areas has significant repercussions on soil nutrient balance. However, how coastal conversion specifically influences the dynamics and stoichiometry of topsoil carbon (C), nitrogen (N), and phosphorus (P) remains limited due to the considerable spatial variability and a lack of comprehensive field data. Here, we investigated the concentration and distribution of total C (TC), N (TN) and P (TP), along with their stoichiometric balance in four distinct coastal landscapes, including natural marshes and tidal flats, as well as converted agricultural croplands and ponds. The results revealed that converted croplands and ponds exhibited significantly higher concentrations of soil C, N and P, particularly in comparison to tidal flats. Furthermore, croplands and ponds have higher topsoil C stocks than tidal flats, but little difference or even lose stored C compared to marshes. Cropland soils showed considerably higher levels of available N (NH4+-N and NO3--N) and available P compared to those in natural marshes and tidal flats. The distribution of soil TC, TN, and TP demonstrated greater spatial heterogeneity in natural marshes and tidal flats, while the converted areas were more uniform and became hotspots for N and P accumulation. Coastal conversion altered soil C:N:P stoichiometry, with cropland soils exhibiting a lower N:P ratio (2.9 ± 1.1), indicating that long-term application of N and P fertilizers could decrease the N:P ratio, as P is more retained in the soil than N. Furthermore, it was observed that the dynamics of C, N and P, as well as their stoichiometry, are closely linked to soil physicochemical properties, especially soil organic matter and texture. These findings highlight that coastal conversion and associated management practices markedly affected soil C, N and P dynamics in a representative wetland area of the subtropical regions, leading to a reshaping of their stoichiometric balances, particularly in the topsoil layer.

Classification and Treatment Strategies of Tibial Tubercle Fractures in Adults.

OBJECTIVES: Tibial tubercle is a crucial player in maintaining the structural integrity and functional stability of the knee joint. Currently, there is no standardized protocol for the classification and treatment of tibial tubercle fractures in adults. This study analyzed the incidence and treatment strategies of tibial tubercle fractures in adults according to the four-column and nine-segment classification system. METHODS: Data of patients with proximal tibial fractures involving tibial tubercle fractures who were treated at our hospital from August 2007 to March 2023 were retrospectively reviewed. The fractures were classified using the AO/OTA classification and four-column and nine-segment classification systems, and the treatment protocol (surgically treated or conservatively treated) was recorded. The number and distribution proportion of patients were counted. A two-sided t-test was conducted to determine the significance of differences between the gender and sides. RESULTS: In total, 169 tibial tubercle fractures were found in 1484 proximal tibial fractures. According to the AO/OTA classification, seven of the 169 patients, (4.1%) were type A, 36 patients (21.3%) were type B, and 126 patients (74.6%) were type C. According to the four-column and nine-segment classification, type 1 cleavage without free fragments was the most common type of fracture (93/169, 55.0%), followed by type 2 dissociative segmental fragments (48/169, 28.4%) and type 3 comminuted fractures (28/169, 16.6%). Overall, 139 of the 169 proximal tibial fractures with tuberosity involvement were treated surgically. Among them, additional fixation of the tubercle fragment was performed in 52 fractures. CONCLUSION: The incidence of tibial tubercle fractures involved in proximal tibial fractures was approximately 11.4% (169/1484) in adults, and approximately one-third of the tubercle bone fragment required additional fixation (30.8%, 52/169). The injury types in the four-column and nine-segment classifications are helpful for accurately judging and making treatment-related decisions for tibial tubercle fractures.

Microbial diversity and keystone species drive soil nutrient cycling and multifunctionality following mangrove restoration.

Vegetation restoration exerts transformative effects on nutrient cycling, microbial communities, and ecosystem functions. While extensive research has been conducted on the significance of mangroves and their restoration efforts, the effectiveness of mangrove restoration in enhancing soil multifunctionality in degraded coastal wetlands remains unclear. Herein, we carried out a field experiment to explore the impacts of mangrove restoration and its chronosequence on soil microbial communities, keystone species, and soil multifunctionality, using unrestored aquaculture ponds as controls. The results revealed that mangrove restoration enhanced soil multifunctionality, with these positive effects progressively amplifying over the restoration chronosequence. Furthermore, mangrove restoration led to a substantial increase in microbial diversity and a reshaping of microbial community composition, increasing the relative abundance of dominant phyla such as Nitrospirae, Deferribacteres, and Fusobacteria. Soil multifunctionality exhibited positive correlations with microbial diversity, suggesting a link between variations in microbial diversity and soil multifunctionality. Metagenomic screening demonstrated that mangrove restoration resulted in a simultaneous increase in the abundance of nitrogen (N) related genes, such as N fixation (nirD/H/K), nitrification (pmoA-amoA/B/C), and denitrification (nirK, norB/C, narG/H, napA/B), as well as phosphorus (P)-related genes, including organic P mineralization (phnX/W, phoA/D/G, phnJ/N/P), inorganic P solubilization (gcd, ppx-gppA), and transporters (phnC/D/E, pstA/B/C/S)). The relationship between the abundance of keystone species (such as phnC/D/E) and restoration-induced changes in soil multifunctionality indicates that mangrove restoration enhances soil multifunctionality through an increase in the abundance of keystone species associated with N and P cycles. Additionally, it was observed that changes in microbial community and multifunctionality were largely associated with shifts in soil salinity. These findings demonstrate that mangrove restoration positively influences soil multifunctionality and shapes nutrient dynamics, microbial communities, and overall ecosystem resilience. As global efforts continue to focus on ecosystem restoration, understanding the complexity of mangrove-soil interactions is critical for effective nutrient management and mangrove conservation.

Skeletal Muscle Satellite Cells Co-Opt the Tenogenic Gene Scleraxis to Instruct Regeneration.

Skeletal muscles connect bones and tendons for locomotion and posture. Understanding the regenerative processes of muscle, bone and tendon is of importance to basic research and clinical applications. Despite their interconnections, distinct transcription factors have been reported to orchestrate each tissue's developmental and regenerative processes. Here we show that Scx expression is not detectable in adult muscle stem cells (also known as satellite cells, SCs) during quiescence. Scx expression begins in activated SCs and continues throughout regenerative myogenesis after injury. By SC-specific Scx gene inactivation (ScxcKO), we show that Scx function is required for SC expansion/renewal and robust new myofiber formation after injury. We combined single-cell RNA-sequencing and CUT&RUN to identify direct Scx target genes during muscle regeneration. These target genes help explain the muscle regeneration defects of ScxcKO, and are not overlapping with Scx -target genes identified in tendon development. Together with a recent finding of a subpopulation of Scx -expressing connective tissue fibroblasts with myogenic potential during early embryogenesis, we propose that regenerative and developmental myogenesis co-opt the Scx gene via different mechanisms.

Coastal degradation regulates the availability and diffusion kinetics of phosphorus at the sediment-water interface: Mechanisms and environmental implications.

Coastal wetlands have experienced considerable loss and degradation globally. However, how coastal degradation regulates sediment phosphorus (P) transformation and its underlying mechanisms remain largely unknown in subtropical coastal ecosystems. This study conducted seasonal field measurements using high-resolution diffusive gradient in thin films (DGT) and dialysis (Peeper) techniques, as well as a DGT-induced fluxes in sediments (DIFS) model, to evaluate the mobilization and diffusion of P along a degradation gradient ranging from pristine wetlands to moderately and severely degraded sites. We observed that sediment P is diminished by coastal degradation, and severely degraded sites exhibit a decline in the concentration of available P, despite the presence of distinct seasonal patterns. High-resolution data based on DGT/Peeper analysis revealed that labile P and soluble reactive P (SRP) concentrations varied from 0.0006 mg L-1 to 0.084 mg L-1 (mean 0.0147 mg L-1) and from 0.0128 mg L-1 to 0.1677 mg L-1 (mean 0.0536 mg L-1), respectively. Coastal degradation had a substantial impact on increasing SRP and labile P concentrations, particularly at severely degraded sites. Although severely degraded wetlands appeared to be P sinks (negative P flux at these sites), we did also observe positive diffusive flux in October, indicating that coastal degradation may accelerate the diffusion and remobilization of sediment P into overlying water. The simulations of the DIFS model provided compelling proof of the high resupply capacity of sediment P at severely degraded sites, as supported by the increased R and k-1 values but decreased Tc values. Taken together, these results suggest coastal degradation reduces the sediment P pool, primarily attributed to the strong remobilization of P from the sediment to porewater and overlying water by enhancing the resupply capability and diffusion kinetics. This acceleration induces nutrient loss which adversely impacts the water quality of the surrounding ecosystem. To reduce the adverse effects of coastal degradation, it is essential to adopt a combination of conservation, restoration, and management efforts designed to mitigate the risk of internal P loading and release, and ultimately maintain a regional nutrient balance.

Network Pharmacology to Reveal the Molecular Mechanisms of Rutaceous Plant-derived Limonin Ameliorating Non-alcoholic Steatohepatitis.

BACKGROUND: Limonin shows promise in alleviating non-alcoholic fatty liver disease. We investigated the mechanisms of limonin against non-alcoholic steatohepatitis (NASH) using network pharmacology and molecular docking. METHODS: Public databases provided NASH- and limonin-associated targets. VennDiagram identified potential limonin targets for NASH. Enrichment analysis explored the limonin-NASH relationship. PPI network analysis, CytoHubba models, and bioinformatics identified hub genes for NASH treatment. Molecular docking assessed limonin's binding ability to hub targets. RESULTS: We found 37 potential limonin targets in NASH, involved in oxidative stress, inflammation, and signaling pathways. PPI network analysis revealed seven hub genes (STAT3, NFKBIA, MTOR, TLR4, CASP8, PTGS2, NFKB1) as NASH treatment targets. Molecular docking confirmed limonin's binding to STAT3, CASP8, and PTGS2. Animal experiments on high-fat diet mice showed limonin reduced hepatic steatosis, lipid accumulation, and expression of p-STAT3/STAT3, CASP8, and PTGS2. CONCLUSION: Limonin's therapeutic effects in NASH may stem from its antioxidant and anti-inflammatory properties. STAT3, CASP8, and PTGS2 are potential key targets for NASH treatment, warranting further investigation.

Safety and efficacy of mesenchymal stem cells in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease-19 (COVID-19) is a zoonotic disease that has become a global pandemic. The fast evolution of the COVID-19 pandemic and persist problems make COVID-19 highly infectious; publicly accessible literature and other sources of information continue to expand in volume. The mesenchymal stem cells (MSCs) therapy efficacy for COVID-19 is debatable. OBJECTIVE: This systematic review and meta-analysis (SRMA) aimed to evaluate the usefulness of MSCs in treating COVID-19. METHODS: Relevant publications were retrieved from databases up to April 30, 2022. In the case of dichotomous data, the 95% confidence intervals (CIs) and pooled risk ratio (RR) were estimated with a random effects model (REM) or fixed effects model (FEM). The pooled mean difference (MD) and 95% CIs were calculated with REM or FEM in continuous data. In the outcomes, studies with insufficient or unusable data were reported descriptively. RESULTS: A total of eight randomized controlled trials (RCTs) with 464 people were chosen for this SRMA. Relative to the control group, mortality was significantly lower in the MSCs group (RR: 0.66, 95% CI: 0.44, 0.99, Z = 2.01, p = .04); other secondary outcomes, such as the clinical symptom improvement rate improved in the MSCs group (RR: 1.44, 95% CI: 1.05, 1.99, Z = 2.24, p = .03), clinical symptom improvement time (MD: -4.01, 95% CI: -6.33, -1.68, Z = 3.38, p = .0007), C-reactive protein (CRP) (MD: -39.16, 95% CI: -44.39, -33.94, Z = 14.70, p < .00001) and days to hospital discharge (MD: -3.83, 95% CI: -6.19, -1.48, Z = 3.19, p = .001) reduced significantly in MSCs group. However, the adverse reaction incidence did not change significantly. CONCLUSIONS: MSCs are a viable therapy option for COVID-19 because of their safety and potential efficacy. With no significant adverse effects, MSCs can reduce mortality, clinical symptom improvement time, and days to hospital discharge, improve clinical symptoms, and reduce inflammatory cytokines CRP in COVID-19. However, further high-quality clinical studies are required to confirm these results.

ZNF143 inhibits hepatocyte mitophagy and promotes non-alcoholic fatty liver disease by targeting increased lncRNA NEAT1 expression to activate ROCK2 pathway.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disorders worldwide. The mitophagy is suggested to be repressed in NAFLD, but the mechanism remains to be elucidated. METHODS: NAFLD cell and mouse models were established by treating with free fatty acid (FFA) and feeding a high fat diet (HFD), respectively. QRT-PCR, Western blotting, or IHC measured the expression of ZNF143, lncRNA NEAT1, ROCK2, and lipid formation/mitophagy-related proteins. Cell viability and mitophagy were evaluated by MTT and immunofluorescence. The chloroform-methanol extraction method measured triglyceride and total cholesterol levels. ELISA detected ALT and AST levels. The interactions among ZNF143, lncRNA NEAT1 and SND1 were analysed by ChIP, dual-luciferase reporter, pull-down, and RIP. The lipid droplets were determined by Oil-red O and HE staining. RESULTS: ZNF143 and lncRNA NEAT1 were upregulated in hepatic cells treated with FFA (p < 0.01 and p < 0.001). Knockdown of ZNF143 or lncRNA NEAT1 inhibited lipid droplets formation, while promoting mitophagy (p < 0.01 and p < 0.001). ZNF143 promoted lncRNA NEAT1 transcriptional expression through binding to its promoter. LncRNA NEAT1 increased ROCK2 mRNA stability by targeting SND1. LncRNA NEAT1 or ROCK2 overexpression reversed the effect of ZNF143 or lncRNA NEAT1 knockdown on hepatic steatosis and mitophagy (p < 0.01 and p < 0.001). ZNF143 or lncRNA NEAT1 knockdown inhibited HFD-induced steatosis and promoted mitophagy in vivo (p < 0.01 and p < 0.001). CONCLUSION: The upregulation of lncRNA NEAT1 caused by ZNF143 promoted NAFLD through inhibiting mitophagy via activating ROCK2 pathway by targeting SND1, providing potential targets for NAFLD therapy.

VGLL4 promotes vascular endothelium specification via TEAD1 in the vascular organoids and human pluripotent stem cells-derived endothelium model.

BACKGROUND: We have shown that Hippo-YAP signaling pathway plays an important role in endothelial cell differentiation. Vestigial-like family member 4 (VGLL4) has been identified as a YAP inhibitor. However, the exact function of VGLL4 in vascular endothelial cell development remains unclear. In this study, we investigated the role of VGLL4, in human endothelial lineage specification both in 3D vascular organoid and 2D endothelial cell differentiation. METHODS AND RESULTS: In this study, we found that VGLL4 was increased during 3D vascular organoids generation and directed differentiation of human embryonic stem cells H1 towards the endothelial lineage. Using inducible ectopic expression of VGLL4 based on the piggyBac system, we proved that overexpression of VGLL4 in H1 promoted vascular organoids generation and endothelial cells differentiation. In contrast, VGLL4 knockdown (heterozygous knockout) of H1 exhibited inhibitory effects. Using bioinformatics analysis and protein immunoprecipitation, we further found that VGLL4 binds to TEAD1 and facilitates the expression of endothelial master transcription factors, including FLI1, to promote endothelial lineage specification. Moreover, TEAD1 overexpression rescued VGLL4 knockdown-mediated negative effects. CONCLUSIONS: In summary, VGLL4 promotes EC lineage specification both in 3D vascular organoid and 2D EC differentiation from pluripotent stem cell, VGLL4 interacts with TEAD1 and facilitates EC key transcription factor, including FLI1, to enhance EC lineage specification.

Linking soil phosphorus availability and phosphatase functional genes to coastal marsh erosion: Implications for nutrient cycling and wetland restoration.

Accelerated marsh erosion caused by climate change and human activity may have important implications for nutrient cycling and availability. However, how erosion affects phosphorus (P) transformation and microbial function in subtropical coastal marshes remains largely unknown. Here we assessed soil P fractions, availability and the phoD-harboring bacterial community along a marsh erosion gradient (non-eroded, lightly eroded, and heavily eroded). We showed that marsh erosion caused a shift in P fractions, leading to a decrease in P availability and a reduction in concentrations of labile P, moderately labile P, and stable P by 20 %, 9 %, and 17 % respectively. The abundance and diversity of phoD phosphatase genes decreased dramatically along the erosion gradient and were lower at heavily eroded sites than at non-eroded sites. Marsh erosion reshaped phoD gene community composition, and Corallococcus, Amycolatopsis, and Phaeobacter were identified as the dominant phoD-harboring microbes. Notably, marsh erosion reduced the complexity and stability of the phoD-harboring bacterial network, and heavily eroded sites have fewer network edges and nodes than non-eroded sites. The dynamics of soil P fractions, availability, and phoD-harboring bacterial communities driven by marsh erosion are largely shaped by substrate availability and soil properties (e.g., nutrients, pH, electrical conductivity, and moisture). Additionally, strong linkages between P availability and the abundance and diversity of phosphatase genes following erosion, suggest that phosphatase drives P mineralization and dissolution, and erosion weakens the regulation of P transformation by reshaping the phoD phosphatase gene community. Our findings indicate that marsh erosion alters soil P fractions and phoD-harboring bacterial communities, which weakens microbial regulation of P transformation and availability, thereby significantly reducing soil P pools and availability. Our findings broaden understanding of the impacts of coastal erosion on nutrient balance and ecosystem function, offering valuable perspectives that could inform wetland restoration and coastal management strategies.

Wdr5-mediated H3K4me3 coordinately regulates cell differentiation, proliferation termination, and survival in digestive organogenesis.

Food digestion requires the cooperation of different digestive organs. The differentiation of digestive organs is crucial for larvae to start feeding. Therefore, during digestive organogenesis, cell identity and the tissue morphogenesis must be tightly coordinated but how this is accomplished is poorly understood. Here, we demonstrate that WD repeat domain 5 (Wdr5)-mediated H3K4 tri-methylation (H3K4me3) coordinately regulates cell differentiation, proliferation and apoptosis in zebrafish organogenesis of three major digestive organs including intestine, liver, and exocrine pancreas. During zebrafish digestive organogenesis, some of cells in these organ primordia usually undergo differentiation without apoptotic activity and gradually reduce their proliferation capacity. In contrast, cells in the three digestive organs of wdr5-/- mutant embryos retain progenitor-like status with high proliferation rates, and undergo apoptosis. Wdr5 is a core member of COMPASS complex to implement H3K4me3 and its expression is enriched in digestive organs from 2 days post-fertilization (dpf). Further analysis reveals that lack of differentiation gene expression is due to significant decreases of H3K4me3 around the transcriptional start sites of these genes; this histone modification also reduces the proliferation capacity in differentiated cells by increasing the expression of apc to promote the degradation of ß-Catenin; in addition, H3K4me3 promotes the expression of anti-apoptotic genes such as xiap-like, which modulates p53 activity to guarantee differentiated cell survival. Thus, our findings have discovered a common molecular mechanism for cell fate determination in different digestive organs during organogenesis, and also provided insights to understand mechanistic basis of human diseases in these digestive organs.

Coral-algal endosymbiosis characterized using RNAi and single-cell RNA-seq.

Corals form an endosymbiotic relationship with the dinoflagellate algae Symbiodiniaceae, but ocean warming can trigger algal loss, coral bleaching and death, and the degradation of ecosystems. Mitigation of coral death requires a mechanistic understanding of coral-algal endosymbiosis. Here we report an RNA interference (RNAi) method and its application to study genes involved in early steps of endosymbiosis in the soft coral Xenia sp. We show that a host endosymbiotic cell marker called LePin (lectin and kazal protease inhibitor domains) is a secreted Xenia lectin that binds to algae to initiate phagocytosis of the algae and coral immune response modulation. The evolutionary conservation of domains in LePin among marine anthozoans performing endosymbiosis suggests a general role in coral-algal recognition. Our work sheds light on the phagocytic machinery and posits a mechanism for symbiosome formation, helping in efforts to understand and preserve coral-algal relationships in the face of climate change.

[Treatment of stage â ¡-â ¢ Kümmell disease with robot-assisted bone cement-augmented pedicle screw fixation].

OBJECTIVE: To evaluate the early clinical efficacy of robot-assisted percutaneous short-segment bone cement-augmented pedicle screw fixation in the treatment of stageⅡ-Ⅲ Kümmell disease. METHODS: The clinical data of 20 patients with stageⅡ-Ⅲ Kümmell's disease who underwent robot-assisted percutaneous bone cement-augmented pedicle screw fixation between June 2017 and January 2021 were retrospectively analyzed. There were 4 males and 16 females, aged from 60 to 81 years old with an average age of (69.1±8.3) years. There were 9 cases of stageⅡand 11 cases of stage Ⅲ, all of which were single vertebral lesions, including 3 cases of T11, 5 cases of T12, 8 cases of L1, 3 cases of L2, and 1 case of L3. These patients did not exhibit symptoms of spinal cord injury. The operation time, intraoperative blood loss, and complications were recorded. The position of pedicle screws and the filling and leakage of bone cement in gaps were observed using postoperative CT 2D reconstruction. The data of the visual analogue scale (VAS), Oswestry disability index (ODI), kyphosis Cobb angle, wedge angle of the diseased vertebra, and anterior and posterior vertebral height on lateral radiographs were statistically analyzed preoperatively, 1 week postoperatively, and at the final follow-up. RESULTS: Twenty patients were followed up for 10 to 26 months, with an average follow-up of (16.0±5.1) months. All operations were successfully completed. The surgical duration ranged from 98 to 160 minutes, with an average of (122±24) minutes. The intraoperative blood loss ranged from 25 to 95 ml, with an average of (45±20) ml. There were no intraoperative vascular nerve injuries. A total of 120 screws were inserted in this group, including 111 screws at grade A and 9 screws at grade B according to the Gertzbein and Robbins scales. Postoperative CT indicated that the bone cement was well-filled in the diseased vertebra, and cement leakage occurred in 4 cases. Preoperative VAS and ODI were (6.05±0.18) points and (71.10±5.37)%, respectively, (2.05±0.14) points and (18.57±2.77)% at 1 week after operation, and (1.35±0.11) points and (15.71±2.12) % at final follow-up. There were significant differences between postoperative 1 week and preoperative, and between final follow-up and postoperative 1 week(P<0.01). Anterior and posterior vertebral height, kyphosis Cobb angle, and wedge angle of the diseased vertebra were(45.07±1.06)%, (82.02±2.11)%, (19.49±0.77) °, and (17.56±0.94) ° preoperatively, respectively, (77.00±0.99)%, (83.04±2.02)%, (7.34±0.56) °, and (6.15±0.52) ° at 1 week postoperatively, and (75.13±0.86)%, (82.39±0.45)%, (8.38±0.63) °, and (7.09±0.59) ° at the final follow-up. CONCLUSION: Robot-assisted percutaneous short-segment bone cement-augmented pedicle screw fixation demonstrates satisfactory short-term efficacy in treating stageⅡ-Ⅲ Kümmell's disease as an effective minimally invasive alternative. However, longer operation times and strict patient selection criteria are necessary, and long-term follow-up is required to determine its lasting effectiveness.

A comparative study of robot-assisted and traditional surgeries in the treatment of thoracolumbar fractures based on 1-year follow-up observation.

BACKGROUND: There are conflicting results for robot-assisted (RA) pedicle screw fixation compared with freehand (FH) pedicle screw fixation. OBJECTIVE: This study was designed to retrospectively compare the accuracy and efficacy of RA percutaneous pedicle screw fixation and traditional freehand FH pedicle screw fixation in the treatment of thoracolumbar fractures. METHODS: A total of 26 cases were assigned to the RA group, and 24 cases were assigned to the FH group. The operation time, bleeding volume, and visual analog scale (VAS) score 1 day after the operation, and the anterior/posterior (A/P) vertebral height ratio of the injured vertebrae at 3 days and at internal fixation removal 1 year after the operation were compared between the two groups. Pedicle screw position accuracy was assessed according to Gertzbein criteria. RESULTS: The operation times of the RA group and FH group were 138.69 ± 32.67 minutes and 103.67 ± 14.53 minutes, respectively, and the difference was statistically significant. The intraoperative blood loss was 49.23 ± 22.56 ml in the RA group and 78.33 ± 23.90 ml in the FH group, and the difference was statistically significant. There was a significant difference in the A/P vertebral height ratio of the injured vertebrae 3 days after the operation compared with before the operation in both groups (P < 0.05). There was a significant difference in the A/P vertebral height ratio of the injured vertebrae 3 days after the operation compared with that at fixation removal in both groups (P < 0.05). CONCLUSION: The application of RA orthopedic treatment for thoracolumbar fractures can achieve good fracture reduction.

The application of a hollow trephine in femoral retrograde intramedullary nailing technique.

PURPOSE: The purpose of this study was to describe and evaluate the use of a specially designed hollow trephine to create the entry point through the femoral condyle during retrograde interlocking intramedullary nailing for femoral fractures. METHODS: From June 2019 to December 2021, we treated 11 patients (5 men, 6 women; mean age, 64 years; age range 40-77 years) with mid-distal femoral fractures by retrograde intramedullary femoral nailing using a self-designed hollow trephine for femoral condyle reaming and cancellous bone harvesting. The mode of all the nails is static. Patients were followed up at 1, 4, 8, and 12 weeks and for at least 6 months after surgery. The healing process and heterotopic ossification were evaluated by imaging. Partial weight bearing was permitted during the recovery period and complete weight bearing was permitted after clinical healing of the fracture displayed by X-ray. RESULTS: The operation was successful in all patients. Over mean follow-up of 9.3 months (range, 6.0-12.0 months), all patients achieved clinical healing within three months. There were no complications such as knee joint infection, heterotopic ossification, knee joint adhesion and wedge effect. CONCLUSION: The use of the hollow trephine during femoral retrograde intramedullary nailing helps avoid postoperative complications such as heterotopic ossification, knee joint adhesions, and wedge effect. It also facilitates bone graft harvesting.

Clinical characteristics and prognosis of pregnancy-related acute kidney injury: a case series study.

OBJECTIVE: Acute kidney injury (AKI) seriously affects the health of both pregnant women and fetuses. This study aimed to investigate the clinical characteristics and prognosis of pregnancy-related AKI (PR-AKI). METHODS: This case series study enrolled pregnant women with PR-AKI admitted to the surgical intensive care unit of Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine between January 2010 and December 2020. RESULTS: Thirty-one PR-AKI patients were enrolled with a mean age of 29.16 ± 4.97 years. Seventeen pregnant women (54.84%) had complete recovery of renal function, 5 (16.13%) had partial recovery of renal function, 2 (6.45%) patients had no renal function improvement, and 7 (22.58%) died. Among the 31 patients with 35 fetuses, 25 (80.6%) pregnant women had poor fetal outcomes, including 5 cases of stillbirths, 5 neonatal asphyxia, 18 premature births, 10 low birth weight, and 8 deficient birth weight infants. Compared to cases with good fetal outcomes, cases with poor fetal outcomes had significantly shorter gestational weeks (39.26 ± 1.53 vs. 31.62 ± 5.50, P = 0.002), lower platelet count (217.13 ± 122.87 vs. 90.24 ± 84.88, P = 0.005), lower hemoglobin (94.19 ± 13.21 vs. 74.48 ± 20.78, P = 0.036), higher blood urea nitrogen (11.87 ± 4.28 vs. 19.47 ± 10.98, P = 0.013), and higher uric acid (262.41 ± 167.00 vs. 586.87 ± 144.52, P < 0.001). CONCLUSIONS: The maternal renal function of women with PR-AKI might improve after treatment, but occurrence rates of adverse fetal outcomes were still high.

Substantial increase in P release following conversion of coastal wetlands to aquaculture ponds from altered kinetic exchange and resupply capacity.

The reclamation of wetlands and its subsequent conversion to aquaculture may alter regional nutrient (im)mobilization and cycling, although direct assessments of phosphorus (P) cycling and its budget balance following wetland conversion are currently scarce. Here, parallel field experiments were conducted to investigate and compare the availability and mobilization mechanisms of P from natural coastal wetlands and the adjacent converted aquaculture ponds based on high-resolution diffusive gradient in thin films (DGT) and dialysis (HR-Peeper) techniques and the DGT-induced fluxes in sediments (DIFS) model. The study found that the conversion of wetland to pond strongly reduced the sediment P pool by changing its forms and distribution. High-resolution data showed that concentrations of labile P and soluble reactive P across the sediment-water profiles were markedly enhanced by the converted aquaculture pond, although they exhibited large spatiotemporal heterogeneity. Moreover, the synchronous distribution of labile P, iron (Fe) and sulfur (S) across profiles in coastal wetlands indicated that the dissolution of Fe (III) oxyhydroxide-phosphate complexes coupled with sulfate reduction were the main mechanisms regulating sediment P mobilization in coastal areas. However, the converted aquaculture pond weakened or even reversed this dependence by decoupling the Fe-S-P reactions by changing the sediment structure and nutrient balance. Substantial increases in labile P, Fe and S fluxes in the pond suggested the conversion of wetland to aquaculture facilitated the internal release of P, Fe and S from sediment into water. The high resupply parameter (R) and desorption rate (k-1) combined with low response time (Tc) in the pond, as fitted by DIFS model, indicated the strong resupply capacity and fast kinetic exchange of sediment P across the sediment-water interface, which is consistent with the high P diffusion fluxes recorded in the pond. It was concluded that converted aquaculture ponds act as an important source of P release in coastal areas, potentially exacerbating water quality degradation and eutrophication. Specific initiatives and actions are therefore urgently needed to alleviate the internal P-loading during aquaculture.

VGLL4-TEAD1 promotes vascular smooth muscle cell differentiation from human pluripotent stem cells via TET2.

The Hippo signaling pathway plays a critical role in cardiovascular development and stem cell differentiation. Using microarray profiling, we found that the Hippo pathway components vestigial-like family member 4 (VGLL4) and TEA domain transcription factor 1 (TEAD1) were upregulated during vascular smooth muscle cell (VSMC) differentiation from H1 ESCs (H1 embryonic stem cells). To further explore the role and molecular mechanisms of VGLL4 in regulating VSMC differentiation, we generated a VGLL4-knockdown H1 ESC line (heterozygous knockout) using the CRISPR/Cas9 system and found that VGLL4 knockdown inhibited VSMC specification. In contrast, overexpression of VGLL4 using the PiggyBac transposon system facilitated VSMC differentiation. We confirmed that this effect was mediated via TEAD1 and VGLL4 interaction. In addition, bioinformatics analysis revealed that Ten-eleven-translocation 2 (TET2), a DNA dioxygenase, is a target of TEAD1, and a luciferase assay further verified that TET2 is the target of the VGLL4-TEAD1 complex. Indeed, TET2 overexpression promoted VSMC marker gene expression and countered the VGLL4 knockdown-mediated inhibitory effects on VSMC differentiation. In summary, we revealed a novel role of VGLL4 in promoting VSMC differentiation from hESCs and identified TET2 as a new target of the VGLL4-TEAD1 complex, which may demethylate VSMC marker genes and facilitate VSMC differentiation. This study provides new insights into the VGLL4-TEAD1-TET2 axis in VSMC differentiation and vascular development.

Coastal wetland conversion to aquaculture pond reduced soil P availability by altering P fractions, phosphatase activity, and associated microbial properties.

Reclamation and conversion of wetlands strongly affect nutrient cycling and ecosystem functions, while little attention has been paid to the effects of converting coastal wetland to aquaculture on the cycling and balance of soil phosphorus (P). Herein, we investigated soil P fractions, alkaline phosphatase (ALP) activity, and associated microbial properties following coastal wetland conversion in subtropical China. Soil P availability (especially resin-P) concentration and ALP activity in wetland were significantly higher than those in pond. The conversion of coastal wetlands to aquaculture significantly reduced the abundance and diversity of bacterial phoD genes and altered their community structure. The lower phosphatase activity and associated microbial properties after wetland conversion suggested a weaker capacity of microbes to transform organic P (Po) to inorganic P (Pi), consistent with the low P availability but the high Po:Pi ratio in pond. Structural equation modeling indicated that the conversion of the wetland to the pond decreased ALP activity and P availability by affecting soil variables such as bulk density, pH, the carbon: nitrogen ratio, and/or moisture. It was concluded that wetland conversion to pond reduced soil P availability and phosphatase activity, altered the abundance, diversity and community composition of the phoD gene, and ultimately affected coastal P cycles and balances. Moreover, an extended corollary is that the smaller amounts of variation in soil total P and lower labile P concentrations in pond than in wetland suggest that large amounts of P (introduced in feed and not harvested in shrimp) are "lost" from the system. Thus, aquaculture ponds might serve as a source of P for the surrounding environment. More investigations focusing on the P biogeochemical cycle and its potential impacts on adjacent ocean environments at regional and global scales is urgently needed, which could contribute to better management of coastal land uses.