LncRNA PSMB8-AS1 Instigates Vascular Inflammation to Aggravate Atherosclerosis.

BACKGROUND: Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA, PSMB8-AS1, has been implicated in the development of tumors. Nevertheless, the precise role of PSMB8-AS1 in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated. Thus, the primary aim of this investigation is to assess the influence of PSMB8-AS1 on vascular inflammation and the initiation of atherosclerosis. METHODS: We generated PSMB8-AS1 knockin and Apoe (Apolipoprotein E) knockout mice (Apoe-/-PSMB8-AS1KI) and global Apoe and proteasome subunit-ß type-9 (Psmb9) double knockout mice (Apoe-/-Psmb9-/-). To explore the roles of PSMB8-AS1 and Psmb9 in atherosclerosis, we fed the mice with a Western diet for 12 weeks. RESULTS: Long noncoding RNA PSMB8-AS1 is significantly elevated in human atherosclerotic plaques. Strikingly, Apoe-/-PSMB8-AS1KI mice exhibited increased atherosclerosis development, plaque vulnerability, and vascular inflammation compared with Apoe-/- mice. Moreover, the levels of VCAM1 (vascular adhesion molecule 1) and ICAM1 (intracellular adhesion molecule 1) were significantly upregulated in atherosclerotic lesions and serum of Apoe-/-PSMB8-AS1KI mice. Consistently, in vitro gain- and loss-of-function studies demonstrated that PSMB8-AS1 induced monocyte/macrophage adhesion to endothelial cells and increased VCAM1 and ICAM1 levels in a PSMB9-dependent manner. Mechanistic studies revealed that PSMB8-AS1 induced PSMB9 transcription by recruiting the transcription factor NONO (non-POU domain-containing octamer-binding protein) and binding to the PSMB9 promoter. PSMB9 (proteasome subunit-ß type-9) elevated VCAM1 and ICAM1 expression via the upregulation of ZEB1 (zinc finger E-box-binding homeobox 1). Psmb9 deficiency decreased atherosclerotic lesion size, plaque vulnerability, and vascular inflammation in Apoe-/- mice in vivo. Importantly, endothelial overexpression of PSMB8-AS1-increased atherosclerosis and vascular inflammation were attenuated by Psmb9 knockout. CONCLUSIONS: PSMB8-AS1 promotes vascular inflammation and atherosclerosis via the NONO/PSMB9/ZEB1 axis. Our findings support the development of new long noncoding RNA-based strategies to counteract atherosclerotic cardiovascular disease.

Selective Vulnerability of GABAergic Inhibitory Interneurons to Bilirubin Neurotoxicity in the Neonatal Brain.

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here we report that bilirubin (BIL)-dependent cell death in auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel mediated current (Ih), or by genetic deletion of HCN1. GABAergic inhibitory interneurons predominantly express HCN1, on which BIL selectively acts to increase their intrinsic excitability and mortality by enhancing HCN1 activity and Ca2+-dependent membrane targeting. Chronic BIL elevation in neonatal mice in vivo increases the fraction of spontaneously active interneurons and their firing frequency, Ih and death, compromising audition at young adult stage in HCN1+/+, but not in HCN1-/- genotype. We conclude that HB preferentially targets HCN1 to injure inhibitory interneurons, fueling a feedforward loop in which lessening inhibition cascades hyperexcitability, Ca2+ overload, neuronal death and auditory impairments. These findings rationalize HCN1 as a potential target for managing HB encephalopathy.Significance Statement This study demonstrated that bilirubin preferentially targets GABAergic interneurons where it facilitates not only gating of HCN1 channels but also targeting of intracellular HCN1 to plasma membrane in calcium-dependent manner, resulting in neuronal hyperexcitability, injury and sensory dysfunction. These findings implicate HCN1 channel not only as a potential driver for auditory abnormalities in neonatal patients with bilirubin encephalopathy, but also potential intervention target for clinical management of neurological impairments associated with severe jaundice. Selective vulnerability of interneurons to neurotoxicity may be of general significance for understanding other forms of brain injury.

INO80-Dependent Remodeling of Transcriptional Regulatory Network Underlies the Progression of Heart Failure.

BACKGROUND: Progressive remodeling of cardiac gene expression underlies decline in cardiac function, eventually leading to heart failure. However, the major determinants of transcriptional network switching from normal to failed hearts remain to be determined. METHODS: In this study, we integrated human samples, genetic mouse models, and genomic approaches, including bulk RNA sequencing, single-cell RNA sequencing, chromatin immunoprecipitation followed by high-throughput sequencing, and assay for transposase-accessible chromatin with high-throughput sequencing, to identify the role of chromatin remodeling complex INO80 in heart homeostasis and dysfunction. RESULTS: The INO80 chromatin remodeling complex was abundantly expressed in mature cardiomyocytes, and its expression further increased in mouse and human heart failure. Cardiomyocyte-specific overexpression of Ino80, its core catalytic subunit, induced heart failure within 4 days. Combining RNA sequencing, chromatin immunoprecipitation followed by high-throughput sequencing, and assay for transposase-accessible chromatin with high-throughput sequencing, we revealed INO80 overexpression-dependent reshaping of the nucleosomal landscape that remodeled a core set of transcription factors, most notably the MEF2 (Myocyte Enhancer Factor 2) family, whose target genes were closely associated with cardiac function. Conditional cardiomyocyte-specific deletion of Ino80 in an established mouse model of heart failure demonstrated remarkable preservation of cardiac function. CONCLUSIONS: In summary, our findings shed light on the INO80-dependent remodeling of the chromatin landscape and transcriptional networks as a major mechanism underlying cardiac dysfunction in heart failure, and suggest INO80 as a potential preventative or interventional target.

Cannabidiol protects against acute aortic dissection by inhibiting macrophage infiltration and PMAIP1-induced vascular smooth muscle cell apoptosis.

Acute aortic dissection (AAD) progresses rapidly and is associated with high mortality; therefore, there remains an urgent need for pharmacological agents that can protect against AAD. Herein, we examined the therapeutic effects of cannabidiol (CBD) in AAD by establishing a suitable mouse model. In addition, we performed human AAD single-cell RNA sequencing and mouse AAD bulk RNA sequencing to elucidate the potential underlying mechanism of CBD. Pathological assays and in vitro studies were performed to verify the results of the bioinformatic analysis and explore the pharmacological function of CBD. In a ß-aminopropionitrile (BAPN)-induced AAD mouse model, CBD reduced AAD-associated morbidity and mortality, alleviated abnormal enlargement of the ascending aorta and aortic arch, and suppressed macrophage infiltration and vascular smooth muscle cell (VSMC) apoptosis. Bioinformatic analysis revealed that the pro-apoptotic gene PMAIP1 was highly expressed in human and mouse AAD samples, and CBD could inhibit Pmaip1 expression in AAD mice. Using human aortic VSMCs (HAVSMCs) co-cultured with M1 macrophages, we revealed that CBD alleviated HAVSMCs mitochondrial-dependent apoptosis by suppressing the BAPN-induced overexpression of PMAIP1 in M1 macrophages. PMAIP1 potentially mediates HAVSMCs apoptosis by regulating Bax and Bcl2 expression. Accordingly, CBD reduced AAD-associated morbidity and mortality and mitigated the progression of AAD in a mouse model. The CBD-induced effects were potentially mediated by suppressing macrophage infiltration and PMAIP1 (primarily expressed in macrophages)-induced VSMC apoptosis. Our findings offer novel insights into M1 macrophages and HAVSMCs interaction during AAD progression, highlighting the potential of CBD as a therapeutic candidate for AAD treatment.

Salvage Surgery for Initially Unresectable HCC With PVTT Converted by Locoregional Treatment Plus Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody.

BACKGROUND: This study aimed to compare the survival outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) who underwent or did not undergo salvage surgery followed by a triple combination conversion treatment consisted of locoregional treatment (LRT), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies. METHODS: The data from 93 consecutive patients with initially unresectable HCC and PVTT across 4 medical centers were retrospectively reviewed. They were converted successfully by the triple combination treatment and underwent or did not undergo salvage resection. The baseline characteristics, conversion schemes, conversion treatment-related adverse events (CTRAEs), overall survival (OS), and progression-free survival (PFS) of the salvage surgery and non-surgery groups were compared. Multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS. Additionally, subgroup survival analysis was conducted by stratification of degree of tumor response and type of PVTT. RESULTS: Of the 93 patients, 44 underwent salvage surgery, and 49 did not undergo salvage surgery. The OS and PFS of the salvage surgery and non-surgery groups were not significantly different (P = .370 and .334, respectively). The incidence and severity of CTRAEs of the 2 groups were also comparable. Subgroup analyses revealed that for patients with complete response (CR) or types III-IV PVTT, there was a trend toward better survival in patients who did not undergo salvage surgery. Multivariate analysis showed that baseline α-fetoprotein and best tumor response per mRECIST criteria were independent prognostic factors for OS and PFS. CONCLUSIONS: For patients with initially unresectable HCC and PVTT who were successfully converted by the triple combination therapy, salvage liver resection may not be necessary, especially for the patients with CR or types III-IV PVTT.

EMP1 correlated with cancer progression and immune characteristics in pan-cancer and ovarian cancer.

This study examines the prognostic role and immunological relevance of EMP1 (epithelial membrane protein-1) in a pan-cancer analysis, with a focus on ovarian cancer. Utilizing data from TCGA, CCLE, and GTEx databases, we assessed EMP1 mRNA expression and its correlation with tumor progression, prognosis, and immune microenvironment across various cancers. Our results indicate that EMP1 expression is significantly associated with poor prognosis in multiple cancer types, including ovarian, bladder, testicular, pancreatic, breast, brain, and uveal melanoma. Immune-related analyses reveal a positive correlation between EMP1 and immune cell infiltration, particularly neutrophils, macrophages, and dendritic cells, as well as high expression of immune checkpoint such as CD274, HAVCR2, IL10, PDCD1LG2, and TGFB1 in most tumors. In vivo experiments confirm that EMP1 promotes ovarian cancer cell proliferation, metastasis, and invasion. In conclusion, EMP1 emerges as a potential prognostic biomarker and therapeutic target in various cancers, particularly ovarian cancer, due to its influence on tumor progression and immune cell dynamics. Further research is warranted to elucidate the precise mechanisms of EMP1 in cancer biology and to translate these findings into clinical applications.

Ionic Liquid Modified Polymer Intermediate Layer for Improved Charge Extraction toward Efficient and Stable Perovskite/Silicon Tandem Solar Cells.

Monolithic perovskite/silicon tandem solar cells have been attracted much attention in recent years. Despite their high performances, the stability issue of perovskite-based devices is recognized as one of the key challenges to realize industrial application. When comes to the perovskite top subcell, the interface between perovskite and electron transporting layers (usually C60) significantly affects the device efficiency as well as the stability due to their poor adhesion. Here, different from the conventional interfacial passivation using metal fluorides, a hybrid intermediate layer is proposed-PMMA functionalized with ionic liquid (IL)-is introduced at the perovskite/C60 interface. The application of PMMA essentially improves the interfacial stability due to its strong hydrophobicity, while adding IL relieves the charge accumulation between PMMA and the perovskite. Thus, an optimal wide-bandgap perovskite solar cells achieves power conversion efficiency of 20.62%. These cells are further integrated as top subcells with silicon bottom cells in a monolithic tandem structure, presenting an optimized PCE up to 27.51%. More importantly, such monolithic perovskite/silicon cells exhibit superior stability by maintaining 90% of initial efficiency after 1200 h under continuous illumination.

Mycorrhizal effects on crop yield and soil ecosystem functions in a long-term tillage and fertilization experiment.

It is well understood that agricultural management influences arbuscular mycorrhizal (AM) fungi, but there is controversy about whether farmers should manage for AM symbiosis. We assessed AM fungal communities colonizing wheat roots for three consecutive years in a long-term (> 14 yr) tillage and fertilization experiment. Relationships among mycorrhizas, crop performance, and soil ecosystem functions were quantified. Tillage, fertilizers and continuous monoculture all reduced AM fungal richness and shifted community composition toward dominance of a few ruderal taxa. Rhizophagus and Dominikia were depressed by tillage and/or fertilization, and their abundances as well as AM fungal richness correlated positively with soil aggregate stability and nutrient cycling functions across all or no-tilled samples. In the field, wheat yield was unrelated to AM fungal abundance and correlated negatively with AM fungal richness. In a complementary glasshouse study, wheat biomass was enhanced by soil inoculum from unfertilized, no-till plots while neutral to depressed growth was observed in wheat inoculated with soils from fertilized and conventionally tilled plots. This study demonstrates contrasting impacts of low-input and conventional agricultural practices on AM symbiosis and highlights the importance of considering both crop yield and soil ecosystem functions when managing mycorrhizas for more sustainable agroecosystems.

Outcomes of Salvage Surgery Versus Non-Salvage Surgery for Initially Unresectable Hepatocellular Carcinoma After Conversion Therapy with Transcatheter Arterial Chemoembolization Combined with Lenvatinib Plus Anti-PD-1 Antibody: A Multicenter Retrospective Study.

BACKGROUND: Combination treatment with transcatheter arterial chemoembolization (TACE), lenvatinib, and anti-programmed death-1 (anti-PD-1) antibodies (triple therapy) has a high rate of tumor response and converted resection for initially unresectable hepatocellular carcinoma (uHCC) patients. This study aimed to assess the outcomes of salvage surgery in uHCC patients after conversion therapy with triple therapy. METHODS: uHCC patients who met the criteria for hepatectomy after receiving triple therapy as first-line treatment were eligible for inclusion in this study. The overall survival (OS) and progression-free survival (PFS) rates in patients who received salvage surgery (SR group) and those who did not (non-SR group) were compared. RESULTS: Of the 144 patients assessed, 91 patients underwent salvage surgery and 53 did not. The OS rates in the SR group were significantly better than those in the non-SR group. The 1- and 2-year OS rates in the SR group were 92.0% and 79.9%, respectively, whereas those in the non-SR group were 85.5% and 39.6 %, respectively (p = 0.007); however, there was no significant difference in the PFS rates. Upon further stratification, OS and PFS were significantly better in the SR group than in the non-SR group in patients who were assessed as partial responses (PR), while there was no significant difference in patients who were assessed as complete response (CR). CONCLUSIONS: Salvage surgery is recommended and is associated with a favorable prognosis for uHCC patients who were assessed as PR after conversion therapy, however it may not be necessary for uHCC if CR was achieved.

Copper-Catalyzed [4+1+1] Annulation of Ammonium Salts and Anthranils: Synthesis of 2,3-Diaroylquinolines.

A copper(I)-catalyzed protocol is developed for the synthesis of various 2,3-diaroylquinolines starting from achiral ammonium salts and anthranils through [4+1+1] annulation. Using copper(I) chloride as the sole catalyst, this reaction is featured with easily available starting materials, broad substrate scope, good yields and simple reaction conditions.

Moxibustion pre-treatment attenuates seizure severity during status epilepticus and counteracts the proconvulsant function of the purinergic P2X7 receptor.

Moxibustion, traditional Chinese medicine treatment, involves the warming of specific acupuncture points of the body using ignited herbal materials. Evidence suggests beneficial effects of moxibustion in several brain diseases including epilepsy, however, whether moxibustion pretreatment impacts on seizures and what are the underlying mechanisms remains to be established. Evidence has suggested the purinergic ATP-gated P2X7 receptor (P2X7R) to be involved in the actions of moxibustion. Moreover, P2X7R signalling is now well established to contribute to long-lasting brain hyperexcitability underlying epilepsy development. Whether P2X7R signalling is involved in the seizure-reducing actions of moxibustion has not been investigated to date. For our studies we used C57BL/6 male mice that received moxibustion pre-treatments at the acupoints Zusanli (ST36) and Dazhui (GV14) once daily for either 7, 14, or 21 days. This was followed by an intraperitoneal injection of kainic acid (KA, 30 mg/kg) to induce status epilepticus. Behavioral changes during KA-induced status epilepticus were analyzed according to the Racine scale. Changes in electrographic seizures were analyzed via cortical implanted electroencephalogram (EEG) electrodes. While no effect on seizure severity was observed following 7 days of moxibustion pre-treatment, moxibustion pre-treatment at both ST36 and GV14 for 14 or 21 days significantly reduced KA-induced behavior seizures at a similar rate. Cortical EEG recordings showed that 14 days of moxibustion pre-treatments also reduced electrographic seizures, confirming the anticonvulsant actions of moxibustion pre-treatment. To determine whether moxibustion impacts the pro-convulsant actions of P2X7R signaling, mice were treated with the P2X7R agonist BzATP or P2X7R antagonist A438079. While treatment with the P2X7R agonist BzATP exacerbated seizure severity, treatment with the P2X7R antagonist reduced seizure severity. We further found that moxibustion pre-treatment attenuated epileptic seizures by counteracting the effects of BzATP. These results suggest that moxibustion pre-treatment at the acupoints ST36 and GV14 for 14 days has anti-epileptic effects, which may counteract the proconvulsant functions of the P2X7R.

Aberrant neural oscillations in poststroke aphasia.

Neural oscillations are electrophysiological indicators of synchronous neuronal activity in the brain. Recent work suggests aberrant patterns of neuronal activity in patients with poststroke aphasia. Yet, there is a lack of systematic explorations of neural oscillations in poststroke aphasia. Investigating changes in the dynamics of neuronal activity after stroke may be helpful to identify neural markers of aphasia and language recovery and increase the current understanding of successful language rehabilitation. This review summarizes research on neural oscillations in poststroke aphasia and evaluates their potential as biomarkers for specific linguistic processes. We searched the literature through PubMed, Web of Science, and EBSCO, and selected 31 studies that met the inclusion criteria. Our analyses focused on neural oscillation activity in each frequency band, brain connectivity, and therapy-induced changes during language recovery. Our review highlights potential neurophysiological markers; however, the literature remains confounded, casting doubt on the reliability of these findings. Future research must address these confounds to confirm the robustness of cross-study findings on neural oscillations in poststroke aphasia.

Elucidating CTLA-4's role in tumor immunity: a comprehensive overview of targeted antibody therapies and clinical developments.

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) emerges as a key single-chain transmembrane glycoprotein predominantly expressed in effector T cells and regulatory T cells. It plays a crucial role in tumor immunity by modulating T cell responses. Specifically, CTLA-4 dampens T cell activation and proliferation while bolstering the survival of regulatory T cell through its competitive interaction with B7 family molecules, thereby aiding tumor cells in eluding immune detection. Given CTLA-4's significant influence on tumor immune dynamics, an array of anti-CTLA-4 antibody therapeutics have been clinically developed to combat various malignancies, including melanoma, renal cell carcinoma, colorectal carcinoma, hepatocellular carcinoma, non-small cell lung carcinoma, and pleural mesothelioma, demonstrating notable clinical therapeutic effects. This paper aims to delve into CTLA-4's integral role in tumor immunity and to encapsulate the latest advancements in the clinical research of anti-CTLA-4 antibody.

Experimental study of rotational relaxation for D2(1,12) in collisions with N2.

The rotational relaxation behavior of D2(1,12) in a D2-N2 mixture was investigated using coherent anti-Stokes Raman scattering (CARS) technique. The rovibrational level v = 1 and J = 12 of D2 was selectively excited through stimulated Raman pumping while monitoring the temporal evolution of population for D2(1, J ≤ 12) molecules using time-resolved CARS spectroscopy. The results demonstrate that the rotational relaxation processes of D2(1,12) encompass both multi-quantum relaxation and continuous single-quantum relaxation. When α, the molar ratio of N2, is less than 0.5, D2(1,12) predominantly undergoes a single quantum relaxation process transition. However, when α ≥ 0.5, the multi-quantum relaxation mechanism gradually predominates. The total rotational relaxation rate coefficients of D2(1,12) collisions with N2 and D2 at 295 K were determined to be 3.974 × 10-14 and 1.179 × 10-14 cm3 s-1, respectively. The temperature dependence of rotational relaxation rate of D2(1,12) was investigated within the temperature range of 295-453 K. With increasing temperature, the dominant relaxation process exhibited an accelerated behavior, while the minor relaxation process remained largely unaffected. The rotational temperature of the D2 molecule at various N2 molar ratios was determined through the utilization of Boltzmann plots. The rotational temperature undergoes a rapid decline within 2 µs, corresponding to the near-resonant rotation-vibration relaxation process of D2(1,12) collisions with N2. The system reaches a quasi-equilibrium state when the delay time is 3 µs. The findings of this study can serve as a valuable empirical basis for further validation of the kinetic theory and simulation.

Short-term associations of particulate matter with different aerodynamic diameters with mortality due to mental disorders and dementia in Ningde, China.

Limited evidence is available regarding the impact of ambient inhalable particulate matter (PM) on mental disorder (MD) or dementia-related deaths, particularly PM1, PM1-2.5, and coarse particles (PM2.5-10). Moreover, individual confounders have rarely been considered. In addition, evidence from low-pollution areas is needed but is inadequate. Using death records from the Death Registration System during 2015-2021 in Ningde, a coastal city in southeast China, we combined a conditional quasi-Poisson model with a distributed lag nonlinear model to estimate the nonlinear and lagged associations of PM exposure with MD or dementia-related deaths in Ningde, China, comprehensively controlling for individual time-invariant confounders using a time-stratified case-crossover design. The attributable fraction and number were calculated to quantify the burden of MD or dementia-related deaths that were related to PMs. We found J-shaped relationships between MD or dementia-related deaths and PMs, with different thresholds of 13, 9, 19, 33 and 12 µg/m3 for PM1, PM1-2.5, PM2.5, PM10 and PM2.5-10. An inter-quartile range increase for PM1, PM1-2.5, PM2.5, PM10 and PM2.5-10 above the thresholds led to an increase of 31.8% (95% confidence interval, 14.3-51.9%), 53.7% (22.4-93.1%), 32.6% (15.0-53.0%), 35.1% (17.7-55.0%) and 25.9% (13.0-40.3%) in MD-related deaths at lag 0-3 days, respectively. The associations were significant in the cool season rather than in the warm season and were significantly greater among people aged 75-84 years than in others. The fractions of MD-related deaths attributable to PM1, PM1-2.5, PM2.5, PM10 and PM2.5-10 were 5.55%, 6.49%, 7.68%, 10.66%, and 15.11%, respectively; however, only some of them could be protected by the concentrations recommended by the World Health Organisation or China grade I standard. Smaller associations and similar patterns were observed between PMs and dementia-related death. These findings suggest stricter standards, and provide evidence for the development of relevant policies and measures.

H3.3B controls aortic dissection progression by regulating vascular smooth muscle cells phenotypic transition and vascular inflammation.

Aortic dissection is a devastating cardiovascular disease with a high lethality. Histone variants maintain the genomic integrity and play important roles in development and diseases. However, the role of histone variants in aortic dissection has not been well identified. In the present study, H3f3b knockdown reduced the synthetic genes expression of VSMCs, while overexpressing H3f3b exacerbated the cellular immune response of VSMCs induced by inflammatory cytokines. Combined RNA-seq and ChIP-seq analyses revealed that histone variant H3.3B directly bound to the genes related to extracellular matrix, VSMC synthetic phenotype, cytokine responses and TGFß signaling pathway, and regulated their expressions. In addition, VSMC-specific H3f3b knockin aggravated aortic dissection development in mice, while H3f3b knockout significantly reduced the incidence of aortic dissection. In term of mechanisms, H3.3B regulated Spp1 and Ccl2 genes, inducing the apoptosis of VSMCs and recruiting macrophages. This study demonstrated the vital roles of H3.3B in phenotypic transition of VSMCs, loss of media VSMCs, and vascular inflammation in aortic dissection.

Nanoclay Drug-Delivery System Loading Potassium Iodide Promotes Endocytosis and Targeted Therapy in Anaplastic Thyroid Cancer.

The rapid proliferative biological behavior of primary foci of anaplastic thyroid cancer (ATC) makes it a lethal tumor. According to the specific iodine uptake capacity of thyroid cells and enhanced endocytosis of ATC cells, we designed a kind of nanoclay drug-loading system and showed a promising treatment strategy for ATC. Introducing potassium iodide (KI) improves the homoaggregation of clay nanoparticles and then affects the distribution of nanoparticles in vivo, which makes KI@DOX-KaolinMeOH enriched almost exclusively in thyroid tissue. Simultaneously, the improvement of dispersibility of KI@DOX-KaolinMeOH changes the target uptake of ATC cells by improving the endocytosis and nanoparticle-induced autophagy, which regulate the production of autolysosomes and autophagy-enhanced chemotherapy, eventually contributing to a tumor inhibition rate of more than 90% in the primary foci of ATC. Therefore, this facile strategy to improve the homoaggregation of nanoclay by introducing KI has the potential to become an advanced drug delivery vehicle in ATC treatment.

A novel discrete linkage-type electrode for radiofrequency-induced intestinal anastomosis.

INTRODUCTION: For decades, radiofrequency (RF)-induced tissue fusion has garnered great attention due to its potential to replace sutures and staples for anastomosis of tissue reconstruction. However, the complexities of achieving high bonding strength and reducing excessive thermal damage present substantial limitations of existing fusion devices. MATERIALS AND METHODS: This study proposed a discrete linkage-type electrode to carry out ex vivo RF-induced intestinal anastomosis experiments. The anastomotic strength was examined by burst pressure and shear strength test. The degree of thermal damage was monitored through an infrared thermal imager. And the anastomotic stoma fused by the electrode was further investigated through histopathological and ultrastructural observation. RESULTS: The burst pressure and shear strength of anastomotic tissue can reach 62.2 ± 3.08 mmHg and 8.73 ± 1.11N, respectively, when the pressure, power and duration are 995 kPa, 160 W and 13 s, and the thermal damage can be controlled within limits. Histopathological and ultrastructural observation indicate that an intact and fully fused stomas with collagenic crosslink can be formed. CONCLUSION: The discrete linkage-type electrode presents favorable efficiency and security in RF-induced tissue fusion, and these results are informative to the design of electrosurgical medical devices with controllable pressure and energy delivery.

A new scoring system for predicting the outcome of hepatocellular carcinoma patients without microvascular invasion-a large-scale multicentre study.

BACKGROUND: The prognosis of HCC patients without MVI (so called M0) is highly heterogeneous and the need for adjuvant therapy is still controversial. METHODS: Patients with HCC with M0 who underwent liver resection (LR) or liver transplantation (LT) as an initial therapy were included. The Eastern Hepatobiliary Surgery Hospital (EHBH)-M0 score was developed from a retrospective cohort to form the training cohort. The classification which was developed using multivariate cox regression analysis was externally validated. RESULTS: The score was developed using the following factors: α-fetoprotein level, tumour diameter, liver cirrhosis, total bilirubin, albumin and aspartate aminotransferase. The score differentiated two groups of M0 patients (≤3, >3 points) with distinct long-term prognoses outcomes (median overall survival (OS), 98.0 vs. 46.0 months; p < 0.001). The predictive accuracy of the score was greater than the other commonly used staging systems for HCC. And for M0 patients with a higher score underwent LR. Adjuvant transcatheter arterial chemoembolization (TACE) was effective to prolong OS. CONCLUSIONS: The EHBH M0 scoring system was more accurate in predicting the prognosis of HCC patients with M0 after LR or LT. Adjuvant therapy is recommended for HCC patients who have a higher score.

USF1 regulated circPRDM4 modulates tumorigenesis and immune escape in chemoresistant cervical cancer.

Cervical cancer (CC) represents a major global health concern, characterized by chemoresistance and immune evasion mechanisms. Circular RNAs (circRNAs), which play a crucial role in cancer pathogenesis, particularly in the case of CC, have gained significant attention. The primary objective of this study was to investigate the functional significance of circRNAs in chemoresistant CC. A significant upregulation of circPRDM4 expression in chemoresistant CC cells. To investigate the functional consequences, we conducted circPRDM4 knockdown experiments, which resulted in the effective blockade of immune escape mechanisms employed by chemoresistant CC cells. Furthermore, circPRDM4 knockdown demonstrated a significant suppression of tumorigenesis in CC cells, highlighting its contribution to the oncogenic potential of CC. Investigating the regulatory mechanisms involved, we found that the transcriptional factor upstream stimulatory factor 1 (USF1) acts as an inducer of circPRDM4 expression. Remarkably, USF1 was found to effectively modulate CC cell immune escape via its interaction with circPRDM4. Moreover, our results revealed that USF1 is intricately involved in CC cell tumorigenesis through the regulation of circPRDM4. Collectively, our study elucidates the significant roles of circPRDM4 and its upstream regulator USF1 in chemoresistant CC cells. These findings underscore the importance of circRNAs in CC pathogenesis and provide valuable insights into the mechanisms underlying immune escape and tumorigenesis.