Noble Metal Nanoparticle-Based Photothermal Therapy: Development and Application in Effective Cancer Therapy.

Photothermal therapy (PTT) is a promising cancer therapy modality with significant advantages such as precise targeting, convenient drug delivery, better efficacy, and minimal adverse effects. Photothermal therapy effectively absorbs the photothermal transducers in the near-infrared region (NIR), which induces the photothermal effect to work. Although PTT has a better role in tumor therapy, it also suffers from low photothermal conversion efficiency, biosafety, and incomplete tumor elimination. Therefore, the use of nanomaterials themselves as photosensitizers, the targeted modification of nanomaterials to improve targeting efficiency, or the combined use of nanomaterials with other therapies can improve the therapeutic effects and reduce side effects. Notably, noble metal nanomaterials have attracted much attention in PTT because they have strong surface plasmon resonance and an effective absorbance light at specific near-infrared wavelengths. Therefore, they can be used as excellent photosensitizers to mediate photothermal conversion and improve its efficiency. This paper provides a comprehensive review of the key role played by noble metal nanomaterials in tumor photothermal therapy. It also describes the major challenges encountered during the implementation of photothermal therapy.

Application of Nanomaterial-Based Sonodynamic Therapy in Tumor Therapy.

Sonodynamic therapy (SDT) has attracted significant attention in recent years as it is an innovative approach to tumor treatment. It involves the utilization of sound waves or ultrasound (US) to activate acoustic sensitizers, enabling targeted drug release for precise tumor treatment. This review aims to provide a comprehensive overview of SDT, encompassing its underlying principles and therapeutic mechanisms, the applications of nanomaterials, and potential synergies with combination therapies. The review begins by introducing the fundamental principle of SDT and delving into the intricate mechanisms through which it facilitates tumor treatment. A detailed analysis is presented, outlining how SDT effectively destroys tumor cells by modulating drug release mechanisms. Subsequently, this review explores the diverse range of nanomaterials utilized in SDT applications and highlights their specific contributions to enhancing treatment outcomes. Furthermore, the potential to combine SDT with other therapeutic modalities such as photothermal therapy (PTT) and chemotherapy is discussed. These combined approaches aim to synergistically improve therapeutic efficacy while mitigating side effects. In conclusion, SDT emerges as a promising frontier in tumor treatment that offers personalized and effective treatment options with the potential to revolutionize patient care. As research progresses, SDT is poised to play a pivotal role in shaping the future landscape of oncology by providing patients with a broader spectrum of efficacious and tailored treatment options.

Multifunctional Nanoplatform for NIR-II Imaging-Guided Synergistic Oncotherapy.

Tumors are a major public health issue of concern to humans, seriously threatening the safety of people's lives and property. With the increasing demand for early and accurate diagnosis and efficient treatment of tumors, noninvasive optical imaging (including fluorescence imaging and photoacoustic imaging) and tumor synergistic therapies (phototherapy synergistic with chemotherapy, phototherapy synergistic with immunotherapy, etc.) have received increasing attention. In particular, light in the near-infrared second region (NIR-II) has triggered great research interest due to its penetration depth, minimal tissue autofluorescence, and reduced tissue absorption and scattering. Nanomaterials with many advantages, such as high brightness, great photostability, tunable photophysical properties, and excellent biosafety offer unlimited possibilities and are being investigated for NIR-II tumor imaging-guided synergistic oncotherapy. In recent years, many researchers have tried various approaches to investigate nanomaterials, including gold nanomaterials, two-dimensional materials, metal sulfide oxides, polymers, carbon nanomaterials, NIR-II dyes, and other nanomaterials for tumor diagnostic and therapeutic integrated nanoplatform construction. In this paper, the application of multifunctional nanomaterials in tumor NIR-II imaging and collaborative therapy in the past three years is briefly reviewed, and the current research status is summarized and prospected, with a view to contributing to future tumor therapy.

KIAA1429 regulates alternative splicing events of cancer-related genes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains one of the most fatal malignancies with high morbidity and mortality rates in the world, whose molecular pathogenesis is incompletely understood. As an RNA-binding protein participating in the processing and modification of RNA, KIAA1429 has been proved to be implicated in the pathogenesis of multiple cancers. However, how KIAA1429 functions in alternative splicing is not fully reported. In the current study, multi-omics sequencing data were used to analyze and decipher the molecular functions and the underlying mechanisms of KIAA1429 in HCC samples. RNA sequencing data (RNA-seq) analysis demonstrated that in HCCLM3 cells, alternative splicing (AS) profiles were mediated by KIAA1429. Regulated AS genes (RASGs) by KIAA1429 were enriched in cell cycle and apoptosis-associated pathways. Furthermore, by integrating the RNA immunoprecipitation and sequencing data (RIP-seq) of KIAA1429, we found that KIAA1429-bound transcripts were highly overlapping with RASGs, indicating that KIAA1429 could globally regulate the alternative splicing perhaps by binding to their transcripts in HCCLM3 cells. The overlapping RASGs were also clustered in cell cycle and apoptosis-associated pathways. In particular, we validated the regulated AS events of three genes using clinical specimens from HCC patients, including the exon 6 of BPTF gene and a marker gene of HCC. In summary, our results shed light on the regulatory functions of KIAA1429 in the splicing process of pre-mRNA and provide theoretical basis for the targeted therapy of HCC.

Phenformin Down-Regulates c-Myc Expression to Suppress the Expression of Pro-Inflammatory Cytokines in Keratinocytes.

The treatment of many skin inflammation diseases, such as psoriasis and atopic dermatitis, is still a challenge and inflammation plays important roles in multiple stages of skin tumor development, including initiation, promotion and metastasis. Phenformin, a biguanide drug, has been shown to play a more efficient anti-tumor function than another well-known biguanide drug, metformin, which has been reported to control the expression of pro-inflammatory cytokines; however, little is known about the effects of phenformin on skin inflammation. This study used a mouse acute inflammation model, ex vivo skin organ cultures and in vitro human primary keratinocyte cultures to demonstrate that phenformin can suppress acute skin inflammatory responses induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in vivo and significantly suppresses the pro-inflammatory cytokines IL-1ß, IL-6 and IL-8 in human primary keratinocytes in vitro. The suppression of pro-inflammatory cytokine expression by phenformin was not directly through regulation of the MAPK or NF-κB pathways, but by controlling the expression of c-Myc in human keratinocytes. We demonstrated that the overexpression of c-Myc can induce pro-inflammatory cytokine expression and counteract the suppressive effect of phenformin on cytokine expression in keratinocytes. In contrast, the down-regulation of c-Myc produces effects similar to phenformin, both in cytokine expression by keratinocytes in vitro and in skin inflammation in vivo. Finally, we showed that phenformin, as an AMPK activator, down-regulates the expression of c-Myc through regulation of the AMPK/mTOR pathways. In summary, phenformin inhibits the expression of pro-inflammatory cytokines in keratinocytes through the down-regulation of c-Myc expression to play an anti-inflammation function in the skin.

Optimization of Ultrasonic Welding Process Parameters to Enhance Weld Strength of 3C Power Cases Using a Design of Experiments Approach.

Ultrasonic welding (UW) is a joining of plastics through the use of heat generated from high-frequency mechanical motion, which is known as an efficient process in many applications, such as textile, packaging, or automotive. UW of thermoplastics has been widely employed in industry since no polymer degradations are found after UW. However, the trial-and-error approach is frequently used to study optimum UW process parameters for new 3C plastic power cases in current industry, resulting in random efforts, wasted time, or energy consumption. In this study, Taguchi methods are used to study optimum UW process parameters for obtaining high weld strength of a plastic power case. The most important control factor influencing the weld strength is amplitude, followed by weld pressure, hold time, and trigger position. The optimum UW process parameters are amplitude of 43.4 µm, weld pressure of 115 kPa, hold time of 0.4 s, and trigger position of 69.95 mm. Finally, the confirmation experiments are performed to verify the optimum process parameters obtained in this study.

Prognostic prediction and immune infiltration analysis based on ferroptosis and EMT state in hepatocellular carcinoma.

Background: Ferroptosis is one of the main mechanisms of sorafenib against hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) plays an important role in the heterogeneity, tumor metastasis, immunosuppressive microenvironment, and drug resistance of HCC. However, there are few studies looking into the relationship between ferroptosis and EMT and how they may affect the prognosis of HCC collectively. Methods: We downloaded gene expression and clinical data of HCC patients from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases for prognostic model construction and validation respectively. The Least absolute shrinkage and selection operator (LASSO) Cox regression was used for model construction. The predictive ability of the model was assessed by Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve. We performed the expression profiles analysis to evaluate the ferroptosis and EMT state. CIBERSORT and single-sample Gene Set Enrichment Analysis (ssGSEA) methods were used for immune infiltration analysis. Results: A total of thirteen crucial genes were identified for ferroptosis-related and EMT-related prognostic model (FEPM) stratifying patients into two risk groups. The high-FEPM group had shorter overall survivals than the low-FEPM group (p<0.0001 in the TCGA cohort and p<0.05 in the ICGC cohort). The FEPM score was proved to be an independent prognostic risk factor (HR>1, p<0.01). Furthermore, the expression profiles analysis suggested that the high-FEPM group appeared to have a more suppressive ferroptosis status and a more active EMT status than the low- FEPM group. Immune infiltration analysis showed that the myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) were highly enriched in the high-FEPM group. Finally, a nomogram enrolling FEPM score and TNM stage was constructed showing outstanding predictive capacity for the prognosis of patients in the two cohorts. Conclusion: In conclusion, we developed a ferroptosis-related and EMT-related prognostic model, which could help predict overall survival for HCC patients. It might provide a new idea for predicting the response to targeted therapies and immunotherapies in HCC patients.

Characterizations of Polymer Gears Fabricated by Differential Pressure Vacuum Casting and Fused Deposition Modeling.

In recent years, polymer gears have gradually become more widely employed in medium or heavy-duty conditions based on weight reduction in transmission systems because of low costs and low noise compared to metal gears. In the current industry, proposing a cost-effective approach to the manufacture of polymer gears is an important research issue. This paper investigates the wear performance of polymer gears fabricated with eight different kinds of materials using differential pressure vacuum casting and additive manufacturing techniques. It was found that both additive manufacturing and differential pressure vacuum casting seem to be an effective and cost-effective method for low-volume production of polymer gears for industrial applications. The gate number of one is the optimal design to manufacture a silicone rubber mold for differential pressure vacuum casting since the weld line of the polymer is only one. Polyurethane resin, 10 wt.% glass fiber-reinforced polylatic acid (PLA), or 10 wt.% carbon fiber-reinforced PLA are suggested for manufacturing gears for small quantity demand based on the deformation and abrasion weight percentage under process conditions of 3000 rpm for 120 min; epoxy resin is not suitable for making gears because part of the teeth will be broken during abrasion testing.

Green Synthesis of Reusable Adsorbents for the Removal of Heavy Metal Ions.

Industrial wastewater often contains heavy metals, like lead, copper, nickel, cadmium, zinc, mercury, arsenic, and chromium. Overdoses of heavy metals will impose a severe threat to human health. Adsorption is the most efficient way of wastewater treatment for eliminating heavy metals. A novel material-reusable hydrogel-based adsorbent was developed in overcoming the regeneration issue. The polyethylene glycol diacrylate-3-sulfopropyl methacrylate potassium salt (PEGDA-SMP) hydrogel performed an ion-exchange rate to remove heavy metals from wastewater in 30-120 min. The adsorption capacity of PEGDA-SMP increases the increasing pH of a solution, in which pH 5 reaches the maximum. Pseudo-second-order adsorption and the Langmuir adsorption model can fully describe the adsorption properties of PEGDA-SMP for heavy metals. PEGDA-SMP prefers to exchange Pb2+ through K+, and its adsorption capacity can achieve 263.158 mg/g. Ag+, Zn2+, Ni2+, and Cu2+ were 227.27, 117.647, 102.041, and 99.010 mg/g, respectively. The hydrated ionic radius of the heavy metal might play an essential role to affect the adsorption preference. The removal efficiency of heavy metals can approach over 95% for each heavy metal. PEGDA-SMP performs rapid desorption and reaches desorption equilibrium in 15 min. After 10 consecutive adsorption-desorption cycles, the adsorption capacity remained over 90%. The hydrogel developed in this study showed reversible heavy metal absorption. Therefore, excellent adsorption-desorption properties of PEGDA-SMP can be potentially extended to industrial wastewater for removing heavy metals.

Circular RNA CDR1as Exerts Oncogenic Properties Partially through Regulating MicroRNA 641 in Cholangiocarcinoma.

It has been found that the circular RNA (circRNA) CDR1as is upregulated in cholangiocarcinoma (CCA) tissues. In this study, we tried to explore the roles of CDR1as in CCA. CDR1as was overexpressed or knocked down in human CCA cells to assess the effects of CDR1as on cell behaviors and tumor xenograft growth. In vitro, the CDR1as level was significantly increased in CCA cell lines. The results showed that CDR1as promoted the cell proliferation, migration, invasion, and activation of the AKT3/mTOR pathway in CCA cells. Moreover, miR-641, a predicted target microRNA (miRNA) of CDR1as, could partially reverse the effects of CDR1as on cell behaviors in CCA cells. Furthermore, CDR1as improved tumor xenograft growth, and it could be attenuated by miR-641 in vivo Additionally, CDR1as expression was inversely correlated with miR-641 in CCA cells, and miR-641 could directly bind with CDR1as and its target genes, the AKT3 and mTOR genes. Mechanistically, CDR1as could bind with miR-641 and accelerate miR-641 degradation, which possibly leads to the upregulation of the relative mRNA levels of AKT3 and mTOR in RBE cells. In conclusion, our findings indicated that CDR1as might exert oncogenic properties, at least partially, by regulating miR-641 in CCA. CDR1as and miR-641 could be considered therapeutic targets for CCA.

CD47 blockade alleviates acute rejection of allogeneic mouse liver transplantation by reducing ischemia/reperfusion injury.

Despite advances in immunosuppressive therapies, acute rejection response is still a serious concern especially in the early phase after liver transplantation. This study aimed to evaluate whether blocking the TSP1-CD47 signaling pathway could attenuate the acute rejection after liver transplantation. An allogeneic mouse orthotopic liver transplantation model (Balb/c→C3H) with prolonged cold ischemic phase was used to induce severe IRI and lethal acute rejection. CD47mAb or isotype matched-control IgG2a was administered to donor liver during graft perfusion. Recipients were sacrificed at 1d, 3d, 5d and 7d after reperfusion. Blood samples were collected to evaluate serum alanine aminotransferase, total bilirubin, HMGB-1,TNF-α, IL-2 and INF-γ level. Flow cytometric analysis was used to detect the strength of innate and adaptive immune response. Liver tissue was obtained for HE, TUNEL staining and F4/80 immumohistochemical staining. Moreover, we conducted a mixed lymphocyte reaction treated with IgG2a or CD47mAb. Mice in CD47mAb-treated group demonstrated improved survival and significantly lower increase in Suzuki score, apoptosis index, acute rejection index, serum alanine aminotransferase, total bilirubin, HMGB-1, TNF-α, IL-2, INF-γ level and the degree of Kupffer cells' activation especially in the early phase of acute rejection. In addition, Pearson's correlation analysis confirmed significant correlation between Suzuki score/ALT and acute rejection index. The in vitro inhibition assay showed that CD47 blockade couldn't directly inhibit recipient lymphocyte proliferation. Based on the evidence that TSP1-CD47 signaling blockade with CD47mAb could alleviate acute rejection by reducing the extent of IRI after liver transplantation indirectly, this study provided a basis for new interventions and management methods to support better transplant outcomes.

Dissociated skin cells regenerate hair follicles in a microwound, "The Punch Assay".

The purpose of this study was to develop a new, easily executed hair follicle regeneration system and assay, which could be further developed for clinical or cosmetic applications. Dissociated epidermal and dermal progenitor cells, isolated either from neonatal C57BL/6 mice or human foetal scalp tissues, were suspended in (10 µL) F12 medium and pipetted into a 1 or 2 mm-diameter punch biopsy wounds on the back skin of immunodeficient mice. At 3 weeks after transplantation, although pigmented mouse hairs could efficiently form at the injection sites with delivery of mouse cells, none hair formed on the host mouse skin at 3 months after delivery of human cells. Under the same conditions, human follicles could be regenerated when the human skin cells were delivered onto a 2 mm size punch created on a reconstituted human skin (hRSK), which previously generated on the back of an immunodeficient mouse, but the efficiency of hair formation was low. We demonstrated that both mouse and human regenerated follicles showed normal histology and differentiation markers; moreover, the cell chasing experiment confirmed that the regenerated hair follicles were formed from transplanted cells. Compared to other current hair reconstituted assays, the Punch Assay is relatively simple and generates normal hair follicles within a smaller wound. We suggest that the punch assay is a better in vivo assay of cell trichogenicity.

TGF-ß- and lipopolysaccharide-induced upregulation of circular RNA PWWP2A promotes hepatic fibrosis via sponging miR-203 and miR-223.

Both transforming growth factor-beta (TGF-ß) and lipopolysaccharide (LPS) can activate hepatic stellate cells (HSCs), thus increasing expressions of alpha smooth muscle actin (α-SMA) and type I collagen alpha 1 (Col1α1) and promoting liver fibrosis. However, whether TGF-ß and LPS have a common downstream reactor remains unclear. Recently, a strong relationship of circular RNAs (circRNAs) and fibrogenesis has been elucidated. In this study, we compared the expressions of several circRNAs in TGF-ß- and LPS-activated HSCs, and found that circ-PWWP2A was upregulated in both TGF-ß- and LPS-activated HSCs and in mouse fibrotic liver tissues. Meanwhile, circ-PWWP2A was positively correlated with HSC activation and proliferation. Two microRNAs, miR-203 and miR-223, were identified to be the downstream targets of circ-PWWP2A using luciferase reporter assay and pull-down interaction assay. Circ-PWWP2A was suggested to promote HSC activation and proliferation via sponging miR-203 and miR-223, and subsequently increasing Fstl1 and TLR4, respectively. Furthermore, downregulating circ-PWWP2A was indicated to alleviate hepatic fibrosis in vivo. In conclusion, our findings indicated that circ-PWWP2A is the common downstream reactor of TGF-ß and LPS in HSC activation, and that circ-PWWP2A plays a critical role in hepatic fibrogenesis via sponging miR-203 and miR-223.

Impact of combined ischemic preconditioning and remote ischemic perconditioning on ischemia-reperfusion injury after liver transplantation.

Ischemic preconditioning (IPC) and remote ischemic perconditioning (RIPer) confer protective effects against liver ischemia-reperfusion injury (IRI), but data about RIPer applying in liver transplantation is lacking. The study aimed to evaluate whether the combination of IPC and RIPer provides reinforced protective effects. C57BL/6 mice (160 pairs) were allocated into four groups: control, subjected to liver transplantation only; IPC, donor hilar was clamped for 10 min followed by 15 min of reperfusion; RIPer, three cycles of occlusion (5 min) and opening (5 min) of femoral vascular bundle were performed before reperfusion; IPC + RIPer, donors and recipients were subjected to IPC and RIPer respectively. Liver tissues were obtained for histological evaluation, TUNEL staining, malondialdehyde assays, GSH-Px assays, and NF-κB p65 protein and Bcl-2/Bax mRNA analyses. Blood samples were used to evaluate ALT, AST, TNF-α, NOx levels and flow cytometry. We found that protective efficacy of RIPer is less than IPC in terms of ALT, TNF-α, GSH-Px and NOx at 2 h postoperation, but almost equivalent at 24 h and 72 h postoperation. Except for Suzuki scores, ALT, Bcl-2/Bax mRNA ratio, other indices showed that combined treatment brought enhanced attenuation in IRI, compared with single treatment, through additive effects on antioxidation, anti-apoptosis, modulation of microcirculation disturbance, and inhibition of innate immune response. This study suggested a combined strategy that could enhance protection against IRI in clinical liver transplantation, otherwise, provided a hint that RIPer's mechanism might be partly or totally different from IPC in humoral pathway.

An Infectious Pseudoaneurysm Caused by Ventricular Septal Defect Occluder in Patent Ductus Arteriosus Closure in a Two-Year-Old Child.

We present a case of an infectious pseudoaneurysm after patent ductus arteriosus (PDA) closure with a ventricular septal defect (VSD) occluder in a two-year-old child. The aneurysm grew rapidly but was successfully removed in time and the patient survived. To our knowledge, this is the first report of an infectious pseudoaneurysm caused by VSD occluder in PDA closure.

Late-Onset Postoperative Junctional Ectopic Tachycardia in Nonsurgical Procedures.

Postoperative junctional ectopic tachycardia (JET) is a narrow complex tachycardia and most frequently occurs during and after surgical repair of certain types of congenital heart defects. Postoperative junctional ectopic tachycardia may produce unfavorable hemodynamics that prolongs stays in the cardiac intensive care unit and hospital, prolongs time on a ventilator, and occasionally requires the use of extracorporeal membrane oxygenation (ECMO) as rescue therapy. The present report describes a rare case of late-onset postoperative junctional ectopic tachycardia, which occurred 13 days after the deployment of a perimembranous ventricular septal defect (PmVSD) occluder in a 17-year-old female teenager. To the best of our knowledge, late-onset postoperative junctional ectopic tachycardia has not previously been reported as a complication in nonsurgical procedures. In this case, the junctional ectopic tachycardia remained resistant to medicines and the haemodynamic imbalance caused a serious life-threatening situation in the patient. The occluder was removed by an emergent thoracotomy; then, the patient was successfully cured by being supported with extracorporeal membrane oxygenation. The findings suggest that during follow-up management, the physician should pay attention postoperatively to junctional ectopic tachycardia even after discharge from the hospital.

Characteristics of mRNA dynamic expression related to spinal cord ischemia/reperfusion injury: a transcriptomics study.

Following spinal cord ischemia/reperfusion injury, an endogenous damage system is immediately activated and participates in a cascade reaction. It is difficult to interpret dynamic changes in these pathways, but the examination of the transcriptome may provide some information. The transcriptome reflects highly dynamic genomic and genetic information and can be seen as a precursor for the proteome. We used DNA microarrays to measure the expression levels of dynamic evolution-related mRNA after spinal cord ischemia/reperfusion injury in rats. The abdominal aorta was blocked with a vascular clamp for 90 minutes and underwent reperfusion for 24 and 48 hours. The simple ischemia group and sham group served as controls. After rats had regained consciousness, hindlimbs showed varying degrees of functional impairment, and gradually improved with prolonged reperfusion in spinal cord ischemia/reperfusion injury groups. Hematoxylin-eosin staining demonstrated that neuronal injury and tissue edema were most severe in the 24-hour reperfusion group, and mitigated in the 48-hour reperfusion group. There were 8,242 differentially expressed mRNAs obtained by Multi-Class Dif in the simple ischemia group, 24-hour and 48-hour reperfusion groups. Sixteen mRNA dynamic expression patterns were obtained by Serial Test Cluster. Of them, five patterns were significant. In the No. 28 pattern, all differential genes were detected in the 24-hour reperfusion group, and their expressions showed a trend in up-regulation. No. 11 pattern showed a decreasing trend in mRNA whereas No. 40 pattern showed an increasing trend in mRNA from ischemia to 48 hours of reperfusion, and peaked at 48 hours. In the No. 25 and No. 27 patterns, differential expression appeared only in the 24-hour and 48-hour reperfusion groups. Among the five mRNA dynamic expression patterns, No. 11 and No. 40 patterns could distinguish normal spinal cord from pathological tissue. No. 25 and No. 27 patterns could distinguish simple ischemia from ischemia/reperfusion. No. 28 pattern could analyze the need for inducing reperfusion injury. The study of specific pathways and functions for different dynamic patterns can provide a theoretical basis for clinical differential diagnosis and treatment of spinal cord ischemia/reperfusion injury.