A retrospective study comparing pharmacomechanical thrombectomy with catheter-directed thrombolysis for acute deep venous thrombosis.

PURPOSE: This study aims to conduct a comparative analysis of the clinical efficacy and safety between pharmacomechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) in the context of acute lower-extremity deep venous thrombosis (LEDVT). MATERIALS AND METHODS: A retrospective review of our institution's patient database spanning from February 2011 to December 2019 was performed to identify cases of acute LEDVT. The patients were categorized into two distinct groups based on the thrombolytic interventions administered: the PMT group, specifically denoting PMT with AngioJet in our investigation, and the CDT group. Comprehensive data sets encompassing patient demographics, risk factors, procedural specifics, thrombolysis grading, and complications were collected. Subsequent follow-up evaluations at the two-year mark post-treatment included assessments of post-thrombotic syndrome (PTS) and the quality of life (QOL). RESULTS: Among the 348 patients identified (mean age: 50.12 ± 15.87 years; 194 females), 200 underwent catheter-directed thrombolysis (CDT) during the early stage (2011 to 2017), while 148 received pharmacomechanical thrombectomy (PMT) between 2017 and 2019. Baseline data between the two groups exhibited no statistically significant differences. Thrombus scores significantly decreased in both cohorts post-therapy (each p < 0.001).Patients subjected to PMT demonstrated higher thrombolysis rates (77.35±9.44% vs 50.85±6.72%), reduced administration of the thrombolytic agent urokinase [20(20-20) vs 350(263-416), p < 0.001], larger limb circumference differences (above the knee: 6.03±1.76cm vs 4.51±1.82cm, p < 0.001; below the knee: 2.90±1.16cm vs 2.51±0.90cm, p < 0.001), and shorter lengths of stay (7.19±3.11 days vs 12.33±4.77 days, p < 0.001). However, the PMT group exhibited a higher decline in hemoglobin levels (13.41±10.59 g/L vs 10.88±11.41 g/L, p = 0.038) and an increase in creatinine levels [9.58(2.32-15.82) umol/L vs 4.53(2.87-6.08) umol/L, p < 0.001] compared to the CDT group. No statistically significant differences were observed in the numbers of balloon angioplasty, stent implantation (each p > 0.050), and minor and major complications between the two groups. At the 1-year follow-up, post-thrombotic syndrome (PTS) occurred in 13.51% of the PMT group compared to 26% of the CDT group (p = 0.025), with a higher incidence of moderate-severe PTS in the CDT group (8% vs 2.7%, p = 0.036). At the 2-year follow-up, PTS was observed in 16.2% of the PMT group and 31.5% in the CDT group, p = 0.004. Preoperative and postoperative D-values of SF-36 PCS and SF-36 MCS showed no statistically significant between-group differences. CONCLUSION: In our institutional experience, both pharmacomechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) have proven to be effective and safe therapeutic approaches for managing acute lower-extremity deep venous thrombosis (LEDVT). PMT, in particular, demonstrated superior efficacy in achieving thrombosis resolution and mitigating the risk of post-thrombotic syndrome, affirming its role as a favorable intervention in this clinical context.

Reversible Constrained Dissociation and Reassembly of MXene Films.

Enabling materials to undergo reversible dynamic transformations akin to the behaviors of living organisms represents a critical challenge in the field of material assembly. The pursuit of such capabilities using conventional materials has largely been met with limited success. Herein, the discovery of reversible constrained dissociation and reconfiguration in MXene films, offering an effective solution to overcome this obstacle is reported. Specifically, MXene films permit rapid intercalation of water molecules between their distinctive layers, resulting in a significant expansion and exhibiting confined dissociation within constrained spaces. Meanwhile, the process of capillary compression driven by water evaporation reinstates the dissociated MXene film to its original compact state. Further, the adhesive properties emerging from the confined disassociation of MXene films can spontaneously induce fusion between separate films. Utilizing this attribute, complex structures of MXene films can be effortlessly foamed and interlayer porosity precisely controlled, using only water as the inducer. Additionally, a parallel phenomenon has been identified in graphene oxide films. This work not only provides fresh insights into the microscopic mechanisms of 2D materials such as MXene but also paves a transformative path for their macroscopic assembly applications in the future.

The experience of shared decision-making for people with asthma: A systematic review and metasynthesis of qualitative studies.

OBJECTIVES: To identify, describe and synthesise the views and experiences of adults living with asthma regarding shared decision-making (SDM) in the existing qualitative literature METHODS: We conducted a comprehensive search of 10 databases (list databases) from inception until September 2023. Screening was performed according to inclusion criteria. Tools from the Joanna Briggs lnstitute were utilised for the purposes of data extraction and synthesis in this study. The data extraction process in this study employed the Capability, Opportunity and Motivation Model of Behaviour (COM-B model) as a framework, and a pragmatic meta-aggregative approach was employed to synthesise the collected results. RESULTS: Nineteen studies were included in the metasynthesis. Three synthesised themes were identified: the capability of people living with asthma, the opportunities of people living with asthma in SDM, and the motivation of the people living with asthma in SDM. CONCLUSIONS: We have identified specific factors influencing people living with asthma engaging in SDM. The findings of this study can serve as a basis for the implementation of SDM in people living with asthma and provide insights for the development of their SDM training programs. The ConQual score for the synthesised findings was rated as low. To enhance confidence, future studies should address dependability and credibility factors. PRACTICE IMPLICATIONS: This review contemplates the implementation of SDM from the perspective of people living with asthma, with the aim of providing patient-centred services for them. The results of this review can benefit the implementation of SDM and facilitate information sharing. It offers guidance for SDM skills training among adults living with asthma, fosters a better doctor-patient relationship and facilitates consensus in treatment decisions, thereby enabling personalised and tailored medical care. PATIENT OR PUBLIC CONTRIBUTION: Three nursing graduate students participated in the data extraction and integration process, with two students having extensive clinical experience that provided valuable insights for the integration.

[Effectiveness of injured vertebra fixation with inclined-long pedicle screws combined with interbody fusion for thoracolumbar fracture dislocation with disc injury].

Objective: To investigate the effectiveness of injured vertebra fixation with inclined-long pedicle screws combined with interbody fusion for thoracolumbar fracture dislocation with disc injury. Methods: Between January 2017 and June 2022, 28 patients with thoracolumbar fracture dislocation with disc injury were underwent posterior depression, the injured vertebra fixation with inclined-long pedicle screws, and interbody fusion. There were 22 males and 6 females, with a mean age of 41.4 years (range, 22-58 years). The causes of injury included falling from height in 18 cases, traffic accident in 5 cases, and bruise in 5 cases. Fracture segment included 1 case of T 11, 7 cases of T 12, 9 cases of L 1, and 11 cases of L 2. According to the American Spinal Injury Association (ASIA) scale, the spinal injuries were graded as grade A in 4 cases, grade B in 2 cases, grade C in 11 cases, and grade D in 11 cases. Preoperative spinal canal encroachment ratio was 17.7%-75.3% (mean, 44.0%); the thoracolumbar injury classification and severity score (TLICS) ranged from 9 to 10 (mean, 9.9). Seventeen patients were associated with other injuries. The time from injury to operation ranged from 1 to 4 days (mean, 2.3 days). The perioperative indicators (operation time, intraoperative blood loss, and the occurrence of complications), clinical evaluation indicators [visual analogue scale (VAS) score and Oswestry Disability Index (ODI)], radiologic evaluation indicators [anterior vertebral height ratio (AVHR), kyphosis Cobb angle (KCA), intervertebral space height (ISH), vertebral wedge angle (VWA), displacement angle (DA), and percent fracture dislocation displacement (PFDD)], neurological function, and interbody fusion were recorded. Results: The operation time was 110-159 minutes (mean, 130.2 minutes). The intraoperative blood loss was 200-510 mL (mean, 354.3 mL). All incisions healed by first intention, and no surgical complications such as wound infection or hematoma occurred. All patients were followed up 12-15 months (mean, 12.7 months). The chest and lumbar pain significantly relieved, VAS scores and ODI after operation were significantly lower than those before operation, and further decreased with the extension of postoperative time, with significant differences ( P<0.05). At last follow-up, the ASIA classification of neurological function of the patients was grade A in 3 cases, grade B in 1 case, grade C in 1 case, grade D in 10 cases, and grade E in 13 cases, which was significantly different from preoperative one ( Z=-4.772, P<0.001). Imaging review showed that AVHR, KCA, ISH, VWA, DA, and PFDD significantly improved at 1 week, 3 months and last follow-up ( P<0.05). There was no significant difference between different time points after operation ( P>0.05). At last follow-up, according to the modified Brantigan score, all patients achieved good intervertebral bone fusion, including 22 complete fusion and 6 good intervertebral fusion with a few clear lines. No complications such as internal fixation failure or kyphosis occurred during follow-up. Conclusion: The injured vertebra fixation with inclined-long pedicle screws combined with interbody fusion is an effective treatment for thoracolumbar fracture dislocation with disc injury, which can correct the fracture dislocation, release the nerve compression, restore the injured vertebral height, and reconstruct spinal stabilization.

The NEDD8 activating enzyme inhibitor MLN4924 mitigates doxorubicin-induced cardiotoxicity in mice.

Doxorubicin (DOX) is a widely utilized chemotherapeutic agent in clinical oncology for treating various cancers. However, its clinical use is constrained by its significant side effects. Among these, the development of cardiomyopathy, characterized by cardiac remodeling and eventual heart failure, stands as a major concern following DOX chemotherapy. In our current investigation, we have showcased the efficacy of MLN4924 in mitigating doxorubicin-induced cardiotoxicity through direct inhibition of the NEDD8-activating enzyme, NAE. MLN4924 demonstrated the ability to stabilize mitochondrial function post-doxorubicin treatment, diminish cardiomyocyte apoptosis, alleviate oxidative stress-induced damage in the myocardium, enhance cardiac contractile function, mitigate cardiac fibrosis, and impede cardiac remodeling associated with heart failure. At the mechanistic level, MLN4924 intervened in the neddylation process by inhibiting the NEDD8 activating enzyme, NAE, within the murine cardiac tissue subsequent to doxorubicin treatment. This intervention resulted in the suppression of NEDD8 protein expression, reduction in neddylation activity, and consequential manifestation of cardioprotective effects. Collectively, our findings posit MLN4924 as a potential therapeutic avenue for mitigating doxorubicin-induced cardiotoxicity by attenuating heightened neddylation activity through NAE inhibition, thereby offering a viable and promising treatment modality for afflicted patients.

Vasorin exocytosed from glioma cells facilitates angiogenesis via VEGFR2/AKT signaling pathway.

Glioma is a highly vascularized tumor of the central nervous system. Angiogenesis plays a predominant role in glioma progression and is considered an important therapeutic target. Our previous study showed that vasorin (VASN), a transmembrane protein, is overexpressed in glioma and promotes angiogenesis; however, the potential mechanism remains unclear. In this study, we found that human vascular endothelial cells (hECs) co-cultured with VASN-overexpressing glioma cells exhibited accelerated migration ability and increased expression of VASN originated from glioma cells. VASN was found in exosomes secreted by glioma cells and could be taken up by hECs. hECs showed more edge filopodia and significantly upregulated expression of endothelial tip cell marker gene and protein levels after co-culture with VASN-overexpressing glioma cells. In clinical glioma tissue and orthotopic transplantation glioma tissue, the vascular density and the number of vascular endothelial cells with a tip cell phenotype in VASN-overexpressed tissues were significantly higher than in tissues with low expression. At the molecular level, VASN interacted with VEGFR2 and caused internalization and autophosphorylation of VEGFR2 protein, and then activated the AKT signaling pathway. Our study collectively reveals the function and mechanism of VASN in facilitating angiogenesis in glioma, providing a new therapeutic target for glioma. Implications: These findings demonstrate that VASN exocytosed from glioma cells enhanced the migration of vascular endothelial cells by VEGFR2/AKT signaling pathway.

Zanubrutinib plus cytarabine in patients with refractory/relapsed primary central nervous system lymphoma.

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare subtype of aggressive extranodal non-Hodgkin lymphoma. Currently, there is no standard of care for the treatment of refractory or relapsed PCNSL (r/r PCNSL). We conducted a prospective single-arm phase II study to evaluate zanubrutinib plus cytarabine for r/r PCNSL. METHODS: Using Simon's two-stage design, we analyzed 34 patients who received high-dose cytarabine (3.0 g/m2 once daily) for 2 days and zanubrutinib (160 mg twice daily) for 21 days each cycle for up to 6 cycles. The study was registered at www.chictr.org.cn as #ChiCTR2000039229. RESULTS: The median follow-up was 19 months. The overall response rate was 64.7% (95% confidence interval (CI), 47.9% to 78.5%) with a complete remission or unconfirmed complete remission rate of 47.1% (16/34) and a partial remission rate of 17.6% (6/34). The median progression-free survival was 4.5 months (95% CI, 1.5 to 9.4) and the median OS was 18 months (95%CI, 9.5 to not estimable). The median duration of the response was 9 months (95%CI, 3.2 to not estimable). The most common treatment-emergent adverse events were thrombocytopenia (55.9%). No treatment-related death occurred. CONCLUSION: Zanubrutinib and cytarabine showed efficacy in r/r PCNSL with an acceptable safety profile.

Genomics of post-bottleneck recovery in the northern elephant seal.

Populations and species are threatened by human pressure, but their fate is variable. Some depleted populations, such as that of the northern elephant seal (Mirounga angustirostris), recover rapidly even when the surviving population was small. The northern elephant seal was hunted extensively and taken by collectors between the early 1800s and 1892, suffering an extreme population bottleneck as a consequence. Recovery was rapid and now there are over 200,000 individuals. We sequenced 260 modern and 8 historical northern elephant seal nuclear genomes to assess the impact of the population bottleneck on individual northern elephant seals and to better understand their recovery. Here we show that inbreeding, an increase in the frequency of alleles compromised by lost function, and allele frequency distortion, reduced the fitness of breeding males and females, as well as the performance of adult females on foraging migrations. We provide a detailed investigation of the impact of a severe bottleneck on fitness at the genomic level and report on the role of specific gene systems.

USP7 as an emerging therapeutic target: A key regulator of protein homeostasis.

Maintaining protein balance within a cell is essential for proper cellular function, and disruptions in the ubiquitin-proteasome pathway, which is responsible for degrading and recycling unnecessary or damaged proteins, can lead to various diseases. Deubiquitinating enzymes play a vital role in regulating protein homeostasis by removing ubiquitin chains from substrate proteins, thereby controlling important cellular processes, such as apoptosis and DNA repair. Among these enzymes, ubiquitin-specific protease 7 (USP7) is of particular interest. USP7 is a cysteine protease consisting of a TRAF region, catalytic region, and C-terminal ubiquitin-like (UBL) region, and it interacts with tumor suppressors, transcription factors, and other key proteins involved in cell cycle regulation and epigenetic control. Moreover, USP7 has been implicated in the pathogenesis and progression of various diseases, including cancer, inflammation, neurodegenerative conditions, and viral infections. Overall, characterizing the functions of USP7 is crucial for understanding the pathophysiology of diverse diseases and devising innovative therapeutic strategies. This article reviews the structure and function of USP7 and its complexes, its association with diseases, and its known inhibitors and thus represents a valuable resource for advancing USP7 inhibitor development and promoting potential future treatment options for a wide range of diseases.

Poling-assisted hydrofluoric acid wet etching of thin-film lithium niobate.

Thin-film lithium niobate (TFLN) has been extensively investigated for a wide range of applications due to continuous advancements in its fabrication methods. The recent emergence of high-fidelity ferroelectric domain poling of TFLN provides an opportunity for achieving a precise pattern control of ferroelectric domains and a subsequent pattern transfer to the TFLN layer using hydrofluoric acid (HF). In this work, we present, to the best of our knowledge, the first demonstration of z-cut TFLN microdisks using a poling-assisted HF wet etching approach. By applying intense electric fields, we are able to induce a domain inversion in the TFLN with a designed microdisk pattern. A HF solution is subsequently utilized to transfer the inverted domain pattern to the TFLN layer with the selective etching of -z LN, ultimately revealing the microdisks.

The Correlation Between Serum Copper and Non-alcoholic Fatty Liver Disease in American Adults: an Analysis Based on NHANES 2011 to 2016.

Copper functions as an essential micronutrient influencing diverse metabolic processes in mammals, encompassing oxidative stress responses, lipid metabolism, and participation in enzymatic reactions. However, the impact of serum copper on non-alcoholic fatty liver disease (NAFLD) remains controversial. Our aim was to explore the precise correlation between serum copper and NAFLD in a large-scale population-based study. A total of 1377 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included in our study. The diagnosis of NAFLD and its progress to advanced liver fibrosis were based on serological indexes. One-way ANOVA, Kruskal-Wallis H test, and Chi-square test were used to access variations between quartiles groups of serum copper. We conducted multivariate-adjusted logistic regression models and subgroup analyses to investigate the association between serum copper and NAFLD, along with several metabolic diseases. Among the 1377 participants, 661 were diagnosed with NAFLD, and 141 of whom were classified into advanced liver fibrosis. Higher serum copper levels (≥ 21.00 µmol/L) were associated with an increased incidence of NAFLD (odds ratio (OR) = 2.07 (1.38-3.10), p < 0.001), as well as advanced liver fibrosis (OR = 2.40 (1.17-5.19), p = 0.025). Moreover, serum copper exhibited a positive correlation with hypertension, overweight, and abdominal obesity, all of which have been identified as risk factors of NAFLD. Additionally, female participants, under the age of 60, and with a higher body mass index (BMI) (> 24.9 kg/m2) emerged as the most vulnerable subgroup concerning the relationship between serum copper and NAFLD. In the U.S. population, a notable association has been identified, linking elevated serum copper to an increased susceptibility for both the onset and progression of NAFLD, along with several metabolic disorders associated with NAFLD. The adverse effects of excess copper warrant attention in the context of public health considerations.

Anterior atlantoaxial motion preservation fixation technique for axis complex fractures (odontoid process with Hangman's fractures) and technique notes.

This study aims to investigate the feasibility and efficacy of anterior atlantoaxial motion preservation fixation (AMPF) in treating axis complex fractures involving the odontoid process fracture and Hangman's fractures with C2/3 instability. A retrospective study was conducted on eight patients who underwent AMPF for axis complex fractures at the General Hospital of Central Theater Command from February 2004 to October 2021. The types of axis injuries, reasons for injuries, surgery time, intraoperative blood loss, spinal cord injury classification (American Spinal Injury Association, ASIA), as well as complications and technical notes, were documented. This study included eight cases of type II Hangman's fracture, five cases of type II and three cases of type III odontoid process fracture. Five patients experienced traffic accidents, while three patients experienced falling injuries. All patients underwent AMPF surgery with an average intraoperative blood loss of 288.75 mL and a duration of 174.5 min. Two patients experienced dysphagia 1 month after surgery. The patients were followed up for an average of 15.63 months. One case improved from C to E in terms of neurological condition, three cases improved from D to E, and four cases remained at E. Bony fusion and Atlantoaxial Motion Preservation were successfully achieved for all eight patients. AMPF is a feasible and effective way for simultaneous odontoid process fracture and Hangman's fractures with C2/3 instability, while preserving atlantoaxial movement.

Treatment of kyphotic deformity in Kümmell's disease through vertebral body screw fixation and intertransverse process grafting: A case report.

RATIONALE: Kümmell's disease, also well acknowledged as delayed posttraumatic vertebral body collapse, it is a rare condition which mainly occurs in elderly people more than 50 years old, with the thoracolumbar junction being mostly affected. PATIENT CONCERNS: In this research, we employed posterior short-segment screw fixation within the injured vertebral region, coupled with intertransverse process bone grafting, to address Kümmell's disease. A 57-year-old female was admitted to our institution with incapacitating back pain and obvious kyphotic deformity. DIAGNOSES: The diagnosis of Kummell disease was mainly depended on clinical symptoms and imaging examinations. INTERVENTIONS: In this research, we employed posterior short-segment screw fixation within the injured vertebral region, coupled with intertransverse process bone grafting, to address Kümmell's disease. OUTCOMES: The patient could walk independently with the help of a thoracolumbosacral orthosis brace on postoperative Day 2. No pains, kyphotic deformity and neurological deficits were observed during the 36 months of postoperative follow-up. These improvements can be visualized through postoperative magnetic resonance imaging and CT scans. Short-segment screw fixation provides short-term stability to the fracture site and accelerates fracture healing. Subsequently, the healed intervertebral and transverse process grafts offer long-term stability, a fact corroborated by postoperative CT scans. LESSONS: In summary, for Kümmell's disease patients exhibiting kyphotic deformity without neurological deficits or compression, posterior short-segment vertebral screw fixation with intertransverse process bone grafting stands as a viable alternative treatment approach.

Percutaneous monoplanar screws versus hybrid fixed axial and polyaxial screws in intermediate screw fixation for traumatic thoracolumbar burst fractures: a case-control study.

BACKGROUND: To compare the clinical and radiological outcomes of monoplanar screws (MSs) versus hybrid fixed axial and polyaxial screws (HSs) in percutaneous short-segment intermediate screw fixation (PSISF) for traumatic thoracolumbar burst fractures (TTBFs) in patients without neurologic impairment. METHODS: A consecutive series of 100 patients with single-segment TTBFs and no neurologic impairment who underwent PSISF with 6 monoplanar screws (MS group) or correct were retrospectively enrolled. The demographic data, radiologic evaluation indicators, perioperative indicators and clinical assessment indicators were analysed between the MS group and HS group. RESULTS: The demographic data and perioperative indicators were not significantly different in the two groups (P > 0.05). The postoperative anterior vertebral height ratio (AVHR), kyphosis Cobb angle (KCA), vertebral wedge angle (VWA) and spinal canal encroachment rate (SCER) were significantly improved in both groups (*P < 0.05). The MS group obtained better correction than the HS group in terms of improvement in the AVHR, KCA and VWA after surgery (*P < 0.05). At the last follow-up, the MS group had less correction loss of AVHR, KCA and VWA (*P < 0.05). The MS group presented greater improvement in the SCER at the last follow-up (*P < 0.05). The visual analogue scale (VAS) score and Oswestry Disability Index (ODI) score of all patients were significantly better postoperatively than those preoperatively (*P < 0.05), and the scores collected at each follow-up visit did not differ significantly between the two groups (P > 0.05). In the MS group, no internal fixation failure was observed during the follow-up period, but, in the HS group, two cases of internal fixation failure were observed at the last follow-up (one case of rod loosening and one case of screw breakage). CONCLUSIONS: Both MSs and HSs fixation are effective treatments for TTBFs and have comparable clinical outcomes. In contrast, MSs fixation can improve the correction effect, better improve the SCER, and further reduce correction loss as well as reduce the incidence of instrumentation failure. Therefore, MSs fixation might be a better option for treating TTBFs in patients without neurological deficits.

ZMIZ2 facilitates hepatocellular carcinoma progression via LEF1 mediated activation of Wnt/ß-catenin pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high lethality rate. ZMIZ2 is a transcriptional co-activator implicated in various human diseases. However, the role and molecular mechanism of ZMIZ2 in HCC remains to be elucidated. METHODS: The expression and prognostic value of ZMIZ2 in HCC was excavated from public databases and explored by bioinformatic analysis. Then the expression of ZMIZ2 and related genes was further validated by quantitative RT-PCR, western blotting, and immunohistochemistry. Loss and gain-of-function experiments were performed in vitro and in vivo to investigate the function of ZMIZ2 in HCC. In addition, transcriptome sequencing and immunoprecipitation was conducted to explore the potential molecular mechanisms of ZMIZ2. RESULTS: ZMIZ2 was highly expressed in HCC and associated with poor prognosis. Silencing ZMIZ2 significantly inhibited HCC cell proliferation, cell cycle process, migration, and invasion in vitro, and also inhibited the progression of HCC in vivo. Additionally, ZMIZ2 expression was correlated with immune cell infiltration in HCC samples. Somatic mutation analysis showed that ZMIZ2 and TP53 mutations jointly affected the progression of HCC. Mechanistically, ZMIZ2 interacted with LEF1 to regulate malignant progression of HCC by activating the Wnt/ß-catenin pathway. CONCLUSION: ZMIZ2 was overexpressed in HCC and associated with poor prognosis. The overexpression of ZMIZ2 was corelated with malignant phenotype, and it facilitated HCC progression via LEF1-mediated activation of the Wnt/ß-catenin pathway. Furthermore, ZMIZ2 could be served as a prognostic biomarker and a new therapeutic target for HCC.

RBM45 reprograms lipid metabolism promoting hepatocellular carcinoma via Rictor and ACSL1/ACSL4.

Reprogramming of lipid metabolism during hepatocarcinogenesis is not well elucidated. Here, we aimed to explore pivotal RNA-binding motif proteins (RBMs) in lipid metabolism and their therapeutic potential in hepatocellular carcinoma (HCC). Through bioinformatic analysis, we identified RBM45 as a critical gene of interest among differentially expressed RBMs in HCC, with significant prognostic relevance. RBM45 influenced the malignant biological phenotype and lipid metabolism of HCC cells. Mechanically, RBM45 promotes de novo lipogenesis in HCC by directly targeting two key enzymes involved in long-chain fatty acid synthesis, ACSL1 and ACSL4. RBM45 also targets Rictor, which has been demonstrated to modulate lipid metabolism profoundly. RBM45 also aided lipid degradation through activating a key fatty acid ß oxidation enzyme, CPT1A. Thus, RBM45 boosted lipid synthesis and decomposition, indicating an enhanced utility of lipid fuels in HCC. Clinically, body mass index was positively correlated with RBM45 in human HCCs. The combination of a PI3K/AKT/mTOR pathway inhibitor in vitro or Sorafenib in orthotopic liver cancer mouse models with shRBM45 has a more significant therapeutic effect on liver cancer than the drug alone. In summary, our findings highlight the versatile roles of RBM45 in lipid metabolism reprogramming and its therapeutic potential in HCC. Lipids induced RBM45 expression. In turn, RBM45 promoted the utility of lipid in HCCs through accelerating both de novo lipogenesis and fatty acid ß oxidation, which required the participation of Rictor, a core component of mTORC2 that has been demonstrated to modulate lipid metabolism potently, as well as ACSL1/ACSL4, two key enzymes of long-chain fatty acid synthesis. When the first-line chemotherapy drug sorafenib is combined with a PI3K/AKT/mTOR pathway inhibitor (MK2206 is an AKT inhibitor, rapamycin is a mTOR inhibitor, and inhibiting RBM45 can significantly inhibit Rictor), cell cycle, proliferation, lipid metabolism reprogramming, and hepatocarcinogenesis can be significantly inhibited, while apoptosis can be significantly enhanced.

Oomycete effector AVRblb2 targets cyclic nucleotide-gated channels through calcium sensors to suppress pattern-triggered immunity.

Transient and rapid increase in cytosolic Ca2+ plays a crucial role in plant-pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI). Cyclic nucleotide-gated channels (CNGCs) have been implicated in mediating this Ca2+ influx; however, their regulatory mechanisms remain poorly understood. Here, we have found that AVRblb2 requires the calmodulin (CaM) and calmodulin-like (CML) proteins as co-factors to interact with the NbCNGCs, resulting in the formation of AVRblb2-CaM/CML-NbCNGCs complex. Furthermore, CaM and CML are dissociated from NbCNGC18 during PTI response to increase Ca2+ influx; however, Avrblb2 inhibits calcium channel activation by disrupting the release of CaM and CML from NbCNGC18. Following recognition of PAMP, NbCNGC18 forms active heteromeric channels with other NbCNGCs, which may give selectivity of CNGC complex against diverse signals for fine-tuning of cytosolic Ca2+ level to mediate appropriate responses. Silencing of multiple NbCNGCs compromised the function of AVRblb2 on the pathogenicity of Phytophthora infestans, confirming that AVRblb2 contributes to pathogen virulence by targeting CNGCs. Our findings provide new insights into the regulation of CNGCs in PTI and the role of pathogen effectors in manipulating host cell physiology to promote infection.

Hierarchical Hollow Carbon Particles with Encapsulation of Carbon Nanotubes for High Performance Supercapacitors.

A novel and sustainable carbon-based material, referred to as hollow porous carbon particles encapsulating multi-wall carbon nanotubes (MWCNTs) (CNTs@HPC), is synthesized for use in supercapacitors. The synthesis process involves utilizing LTA zeolite as a rigid template and dopamine hydrochloride (DA) as the carbon source, along with catalytic decomposition of methane (CDM) to simultaneously produce MWCNTs and COx -free H2 . The findings reveal a distinctive hierarchical porous structure, comprising macropores, mesopores, and micropores, resulting in a total specific surface area (SSA) of 913 m2  g-1 . The optimal CNTs@HPC demonstrates a specific capacitance of 306 F g-1 at a current density of 1 A g-1 . Moreover, this material demonstrates an electric double-layer capacitor (EDLC) that surpasses conventional capabilities by exhibiting additional pseudocapacitance characteristics. These properties are attributed to redox reactions facilitated by the increased charge density resulting from the attraction of ions to nickel oxides, which is made possible by the material's enhanced hydrophilicity. The heightened hydrophilicity can be attributed to the presence of residual silicon-aluminum elements in CNTs@HPC, a direct outcome of the unique synthesis approach involving nickel phyllosilicate in CDM. As a result of this synthesis strategy, the material possesses excellent conductivity, enabling rapid transportation of electrolyte ions and delivering outstanding capacitive performance.

Functional polymeric molecules for performing autonomous synthesis of particles with core-shell structures and customizable shapes.

Self-organization by the directed migration of components within a system is an important process in many applications, such as the unidirectional migration of motor proteins for transporting items to specific sites in a cell. This manuscript describes a class of functional polymeric molecules that have a set of instructions written by specific chemical moieties. These instructions allow the functional polymeric molecules to be used for autonomous synthesis of particles: particles with both functional core-shell structure and customizable shapes are fabricated for the first time. The functional polymeric molecules direct the large-scale migration of the liquid molecules to specific sites for forming the required customized structure of the particle, thus overcoming previous challenges of fabricating this class of particles. This first synthesis of this class of particles enables the development of novel applications: the concept of shape specificity for targeting sites. Both the basic structural properties (core-shell structure and customizable shape) are used in the specific applications of targeted drug delivery and imaging. The secure physical fit due to the complementary shapes enables the particles to remain locked in position for the targeting. Polymeric molecules are first shown to be highly capable of being encoded with instructions for autonomous synthesis of structured materials.

Global characteristics and trends in research on Candida auris.

Introduction: Candida auris, a fungal pathogen first reported in 2009, has shown strong resistance to azole antifungal drugs and has caused severe nosocomial outbreaks. It can also form biofilms, which can colonize patients' skin and transmit to others. Despite numerous reports of C. auris isolation in various countries, many studies have reported contradictory results. Method: A bibliometric analysis was conducted using VOSviewer to summarize research trends and provide guidance for future research on controlling C. auris infection. The analysis revealed that the United States and the US CDC were the most influential countries and research institutions, respectively. For the researchers, Jacques F. Meis published the highest amount of related articles, and Anastasia P. Litvintseva's articles with the highest average citation rate. The most cited publications focused on clade classification, accurate identification technologies, nosocomial outbreaks, drug resistance, and biofilm formation. Keyword co-occurrence analysis revealed that the top five highest frequencies were for 'drug resistance,' 'antifungal susceptibility test,' 'infection,' 'Candida auris,' and 'identification.' The high-frequency keywords clustered into four groups: rapid and precise identification, drug resistance research, pathogenicity, and nosocomial transmission epidemiology studies. These clusters represent different study fields and current research hotspots of C. auris. Conclusion: The bibliometric analysis identified the most influential country, research institution, and researcher, indicating current research trends and hotspots for controlling C. auris.