Minimally Invasive Delivery of Percutaneous Ablation Agent via Magnetic Colloidal Hydrogel Injection for Treatment of Hepatocellular Carcinoma.

Percutaneous thermotherapy, a minimally invasive operational procedure, is employed in the ablation of deep tumor lesions by means of target-delivering heat. Conventional thermal ablation methods, such as radiofrequency or microwave ablation, to a certain extent, are subjected to extended ablation time as well as biosafety risks of unwanted overheating. Given its effectiveness and safety, percutaneous thermotherapy gains a fresh perspective, thanks to magnetic hyperthermia. In this respect, an injectable- and magnetic-hydrogel-construct-based thermal ablation agent is likely to be a candidate for the aforementioned clinical translation. Adopting a simple and environment-friendly strategy, a magnetic colloidal hydrogel injection is introduced by a binary system comprising super-paramagnetic Fe3O4 nanoparticles and gelatin nanoparticles. The colloidal hydrogel constructs, unlike conventional bulk hydrogel, can be easily extruded through a percutaneous needle and then self-heal in a reversible manner owing to the unique electrostatic cross-linking. The introduction of magnetic building blocks is exhibited with a rapid magnetothermal response to an alternating magnetic field. Such hydrogel injection is capable of generating heat without limitation of deep penetration. The materials achieve outstanding therapeutic results in mouse and rabbit models. These findings constitute a new class of locoregional interventional thermal therapies with minimal collateral damages.

Novel 532-nm Q-switched Nd: YAG laser for the treatment of melasma and rejuvenation: a prospective, randomized controlled comparison with 1,064-nm Q-switched Nd: YAG laser.

BACKGROUND: Melasma is a common pigmentary and photoaging disorder. Although various treatments, including 1,064-nm Q-switched neodymium-doped yttrium aluminum garnet (QS-Nd: YAG) laser toning, are available for melasma, results are often unsatisfactory. OBJECTIVE: We aimed to determine the efficacy and safety of 532-nm QS-Nd: YAG laser (shortwave toning) in patients with melasma and facial rejuvenation. METHODS: Fifty-two patients were recruited to receive either 1,064-nm QS-Nd: YAG laser or 532-nm QS-Nd: YAG laser every 2 weeks for 8 sessions and a 2-month follow-up visit in a randomized controlled double-blinded study. The primary outcome measure was the Melasma Area and Severity Index (MASI) score. Dermoscope and high-frequency ultrasound (HFUS) were used to assess the improvement of melasma and photoaging. RESULTS: 532-nm QS-Nd: YAG laser achieved significantly higher improvement in the MASI score (P = 0.000). The Dermoscopic melasma score (DMS) displayed significant change and confirmed the improvement. HFUS showed a significant decrease in the thickness of the subepidermal low-echogenic band (SLEB) and increases in dermal thickness and dermal density in both groups (P = 0.000 for all). The rate of very satisfied responses was significantly higher in the 532-nm laser group (P = 0.001). There was no significant difference in the visual analog scale pain assessment score (P = 0.248) and recurrence rate (P = 0.734) between the two groups. CONCLUSION: 532-nm QS-Nd: YAG laser (shortwave toning) proved to be an effective and safe treatment for melasma and rejuvenation. Shortwave toning was significantly better for pigmentation clearance, while 1,064-nm laser showed better improvement in skin rejuvenation.

Silver Nanowire Reinforced Conductive and Injectable Colloidal Gel for Effective Wound Healing via Electrical Stimulation.

The remarkable biocapacity, injectability, and adaptability of colloidal gels have led to their widespread usage in tissue engineering as irregular defect implants. However, multifunctionalities including electroconductivity and antibacterial property are highly required for colloidal gels. In addition, the inherently weak mechanical property of physically crosslinked colloidal gels limits their application. Herein, we present Ag nanowires (Ag NWs)-reinforced colloidal gels composed of biocompatible gelatin nanoparticles and polydopamine-modified Ag NWs through the controlled electrostatic assembly, which are injectable and conductive. One-dimensional Ag NWs can significantly improve the mechanical and electrical properties of the colloidal gel while maintaining its inherent excellent injectability. Owing to the network of Ag NWs, the storage modulus and conductivity of the optimized Ag NW colloidal gel are 7.5 and 13 times higher, respectively, than those of the colloidal gel made up of polydopamine-modified Ag nanoparticles with equivalent Ag concentration. Furthermore, this Ag NW colloidal gel can adapt to sharp wounds on skin, which accelerates the healing of a MRSA-infected wound via electrical stimulation. This article is protected by copyright. All rights reserved.

Identification of Critical Amino Acids of Coxsackievirus A10 Associated with Cell Tropism and Viral RNA Release during Uncoating.

Coxsackievirus A10 (CV-A10) is a prevailing causative agent of hand-foot-mouth disease, necessitating the isolation and adaptation of appropriate strains in cells allowed for human vaccine development. In this study, amino acid sequences of CV-A10 strains with different cell tropism on RD and Vero cells were compared. Various amino acids on the structural and non-structural proteins related to cell tropism were identified. The reverse genetic systems of several CV-A10 strains with RD+/Vero- and RD+/Vero+ cell tropism were developed, and a set of CV-A10 recombinants were produced. The binding, entry, uncoating, and proliferation steps in the life cycle of these viruses were evaluated. P1 replacement of CV-A10 strains with different cell tropism revealed the pivotal role of the structural proteins in cell tropism. Further, seven amino acid substitutions in VP2 and VP1 were introduced to further investigate their roles played in cell tropism. These mutations cooperated in the growth of CV-A10 in Vero cells. Particularly, the valine to isoleucine mutation at the position VP1-236 (V1236I) was found to significantly restrict viral uncoating in Vero cells. Co-immunoprecipitation assays showed that the release of viral RNA from the KREMEN1 receptor-binding virions was restricted in r0195-V1236I compared with the parental strain r0195 (a RD+/Vero+ strain). Overall, this study highlights the dominant effect of structural proteins in CV-A10 adaption in Vero cells and the importance of V1236 in viral uncoating, providing a foundation for the mechanism study of CV-A10 cell tropism, and facilitating the development of vaccine candidates.

Cutaneous Adverse Events and Cancer Survival Prognosis With Immune Checkpoint Inhibitor Treatment: A Systematic Review and Meta-Analysis.

Importance: Growing research suggests that the prevalence of cutaneous immune-related adverse events (cirAEs) is associated with favorable outcomes among individuals with cancer who receive immune checkpoint inhibitor (ICI) treatment. Objective: To identify whether the presence of cirAEs and their subtypes subsequent to ICI administration is associated with enhanced cancer prognosis. Data Sources: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for publications examining the association between cirAE development during ICI treatment and subsequent cancer prognosis. The initial search was limited to English-language publications from database inception until December 31, 2022; a subsequent search was performed on May 21, 2023. Study Selection: Two reviewers independently scrutinized the identical articles and included those that constituted original research evaluating the association between cirAE development and cancer prognosis. Data Extraction and Synthesis: The search terms, study objectives, and methodological protocols were defined before study initiation. The aforementioned 2 reviewers performed data extraction independently and resolved discrepancies through agreement. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis and the Meta-analysis of Observational Studies in Epidemiology reporting guidelines. The protocol was prospectively registered with PROSPERO. Data analyses were conducted between May 21 and June 1, 2023. Main Outcomes and Measures: The major outcome end points were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were also conducted according to cirAE type, cancer type, geographic region, study design, and ICI type. Given the heterogeneity inherent in the included studies, a DerSimonian-Laird random-effects model was adopted. Results: This systematic review and meta-analysis included 23 studies with a total of 22 749 patients treated with ICIs. The occurrence of cirAEs was associated with improved OS (hazard ratio [HR], 0.61 [95% CI, 0.52-0.72]; P < .001) and PFS (HR, 0.52 [95% CI, 0.41-0.65]; P < .001). Consistent results were observed across all subgroups stratified by study design, geographic region, ICI type, and cancer type, aligning with the overall estimate of OS and PFS improvement. However, no statistically significant differences were identified in terms of PFS within studies conducted in the US. Conclusions and Relevance: In this systematic review and meta-analysis, the presence of cirAEs and their subtypes was associated with improved prognosis for individuals with cancer undergoing ICI treatment. These findings suggest that cirAEs may have useful prognostic value in ICI treatment.

The Pythium periplocum elicitin PpEli2 confers broad-spectrum disease resistance by triggering a novel receptor-dependent immune pathway in plants.

Elicitins are microbe-associated molecular patterns produced by oomycetes to elicit plant defense. It is still unclear whether elicitins derived from non-pathogenic oomycetes can be used as bioactive molecules for disease control. Here, for the first time we identify and characterize an elicitin named PpEli2 from the soil-borne oomycete Pythium periplocum, which is a non-pathogenic mycoparasite colonizing the root ecosystem of diverse plant species. Perceived by a novel cell surface receptor-like protein, REli, that is conserved in various plants (e.g. tomato, pepper, soybean), PpEli2 can induce hypersensitive response cell death and an immunity response in Nicotiana benthamiana. Meanwhile, PpEli2 enhances the interaction between REli and its co-receptor BAK1. The receptor-dependent immune response triggered by PpEli2 is able to protect various plant species against Phytophthora and fungal infections. Collectively, our work reveals the potential agricultural application of non-pathogenic elicitins and their receptors in conferring broad-spectrum resistance for plant protection.

Efficacy and safety of acupuncture in the treatment of the sequela of olfactory disorders after infection with COVID-19: A protocol for systematic review and meta analysis.

BACKGROUND: From the end of 2019 to now, coronavirus disease 2019 (COVID-19) has put enormous strain on the world's health systems. As a characteristic sign of COVID-19 patient, olfactory dysfunction (OD) poses considerable problems for patients. In China, acupuncture has been widely used to treat OD caused by COVID-19, but there is still a lack of evidence-based medical evaluation. This study was designed to evaluate the effectiveness and safety of acupuncture for the treatment of COVID-19 OD. METHODS: According to the retrieval strategies, randomized controlled trials on the acupuncture for COVID-19 OD were obtained from Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database and the Wanfang Database, regardless of publication date, or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the studies. The meta-analysis was performed using Review Manager (RevMan 5.3) and STATA 14.2 software. Ultimately, the evidentiary grade for the results will be evaluated. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide up-to-date summary proof for evaluating the effectiveness and safety of acupuncture for COVID-19 OD.

Efficacy of adalimumab in pediatric generalized pustular psoriasis: case series and literature review.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, severe, and sometimes fatal form of childhood psoriasis. The first line therapies include acitretin, cyclosporin A, and methotrexate which take effect slowly and have varying long-term side effects for children. Recently, the anti-tumor necrosis factor-alpha (TNF-α), adalimumab has shown efficacy in adult patients with pustular psoriasis; however, there is lack of evidence of its usage in the pediatric population. METHODS: Data on efficacy of adalimumab in treating pediatric GPP along with a literature review are presented. RESULTS: A total of seven patients had marked clearance and reduction in PGA and systemic/laboratory score within the first week of first injection and achieved almost complete clearance of skin lesions by 1-month follow up. In literature, adalimumab treating pustular psoriasis in pediatric has been described in six children who failed in prior treatment. All six patients showed a satisfactory therapeutic effect. CONCLUSIONS: Subcutaneous injection of adalimumab every other week in the treatment of children with GPP has significant clinical efficacy with rapid clearance of skin lesions, providing a novel alternative for children with pustular psoriasis who responded poorly to traditional treatment or are not suitable for traditional treatment.

Electron transport layer assisted by nickel chloride hexahydrate for open-circuit voltage improvement in MAPbI3 perovskite solar cells.

SnO2 is a promising electron transport layer (ETL) material with important applications in planar perovskite solar cells (PSCs). However, electron-hole recombination and charge extraction between SnO2 and the perovskite layer necessitates further exploration. Nickel chloride hexahydrate (NiCl2·6H2O) was introduced into the SnO2 ETL, which significantly increased the power conversion efficiency (PCE) from 15.49 to 17.36% and the open-circuit voltage (V OC) from 1.078 to 1.104 V. The improved PCE and V OC were attributed to the reduced defect states and increased energy level of the conduction band minimum. This work provides new insights into optimizing the V OC and PCE of PSCs.

pH-redox responsive cascade-targeted liposomes to intelligently deliver doxorubicin prodrugs and lonidamine for glioma.

To synergistically treat glioma with a combination chemotherapy, we design and prepare novel cascade-targeted liposomes (Lip-TPGS) using glucose and triphenylphosphonium (TPP) as targeting moieties, which could intelligently deliver redox-sensitive doxorubicin (DOX) prodrugs (SDOX) and chemotherapeutic sensitizer lonidamine (LND). The pH-responsive ligand Chol-TPG modified by PEGylated glucose can overcome the blood-brain barrier and reach tumor cells. Combined with the modification of mitochondria targeting ligand (Chol-TPP), Lip-TPGS are endowed with pH-responsive charge regulation function and multi-stage targeting abilities. After triggered by the excessive glutathione in tumor cells, Lip-TPGS could sufficiently release the parent drugs DOX, which would significantly reduce side effects without compromising anti-glioma efficacy. Therefore, Lip-TPGS possess these characteristics: good pharmacokinetic behavior, superior brain targeting ability, specific tumor recognition and internalization capability, and strong endo/lysosome escaping and mitochondria targeting potential. Furthermore, Lip-TPGS exhibit significant advantages on anti-glioma by inhibiting proliferation, promoting apoptosis, inducing mitochondria dysfunction, inhibiting migration and invasion, prolonging the survival time, narrowing tumor areas, limiting lung metastasis, and reducing toxicity to normal organs. In summary, Lip-TPGS, with cascade targeting abilities from tissue/cell to organelle levels and highly controlled drug release properties, would become a promising drug delivery system for glioma treatment.

Enhanced crystallization of solution-processed perovskite using urea as an additive for large-grain MAPbI3perovskite solar cells.

Perovskite crystal quality plays an important role in perovskite solar cells, given that multiple grain boundaries and trap states in the perovskite films hamper further enhancement of solar cell efficiency. Using the solution method to prepare perovskite films with large grains and high coverage requires further improvements. Herein, we introduce Lewis base urea as an additive into the precursor of perovskite to control the crystallization dynamics, allowing for large-grain crystal growth. As a result, MAPbI3films with urea as an additive are well crystallized with large crystal grains of sizes >3µm. The large-grain perovskite is found to simultaneously improve the power-conversion efficiency (PCE) and device stability. With an optimal urea additive of 20 mol%, the PCE is significantly increased from 15.47% for the reference MAPbI3solar cell to 18.53% for the device with MAPbI3with urea as an additive. Finally, the optimized device demonstrates excellent stability and maintains 80% of the initial PCE after 60 days.

Filamentous Phytophthora Pathogens Deploy Effectors to Interfere With Bacterial Growth and Motility.

Phytophthora comprises a group of filamentous plant pathogens that cause serious crop diseases worldwide. It is widely known that a complex effector repertoire was secreted by Phytophthora pathogens to manipulate plant immunity and determine resistance and susceptibility. It is also recognized that Phytophthora pathogens may inhabit natural niches within complex environmental microbes, including bacteria. However, how Phytophthora pathogens interact with their cohabited microbes remains poorly understood. Here, we present such an intriguing case by using Phytophthora-bacteria interaction as a working system. We found that under co-culture laboratory conditions, several Phytophthora pathogens appeared to block the contact of an ecologically relevant bacterium, including Pseudomonas fluorescence and a model bacterium, Escherichia coli. We further observed that Phytophthora sojae utilizes a conserved Crinkler (CRN) effector protein, PsCRN63, to impair bacterial growth. Phytophthora capsici deploys another CRN effector, PcCRN173, to interfere with bacterial flagellum- and/or type IV pilus-mediated motility whereas a P. capsici-derived RxLR effector, PcAvh540, inhibits bacterial swimming motility, but not twitching motility and biofilm formation, suggesting functional diversification of effector-mediated Phytophthora-bacteria interactions. Thus, our studies provide a first case showing that the filamentous Phytophthora pathogens could deploy effectors to interfere with bacterial growth and motility, revealing an unprecedented effector-mediated inter-kingdom interaction between Phytophthora pathogens and bacterial species and thereby uncovering ecological significance of effector proteins in filamentous plant pathogens besides their canonical roles involving pathogen-plant interaction.

Prediction and Characterization of RXLR Effectors in Pythium Species.

RXLR effectors, a class of secreted proteins that are transferred into host cells to manipulate host immunity, have been reported to widely exist in oomycetes, including those from genera Phytophthora, Hyaloperonospora, Albugo, and Saprolegnia. However, in Pythium species, no RXLR effector has yet been characterized, and the origin and evolution of such virulent effectors are still unknown. Here, we developed a modified regular expression method for de novo identification of RXLRs and characterized 359 putative RXLR effectors in nine Pythium species. Phylogenetic analysis revealed that all oomycetous RXLRs formed a single superfamily, suggesting that they might have a common ancestor. RXLR effectors from Pythium and Phytophthora species exhibited similar sequence features, protein structures, and genome locations. In particular, there were significantly more RXLR proteins in the mosquito biological control agent P. guiyangense than in the other eight Pythium species, and P. guiyangense RXLRs might be the result of gene duplication and genome rearrangement events, as indicated by synteny analysis. Expression pattern analysis of RXLR-encoding genes in the plant pathogen P. ultimum detected transcripts of the majority of the predicted RXLR genes, with some RXLR effectors induced in infection stages and one RXLR showing necrosis-inducing activity. Furthermore, all predicted RXLR genes were cloned from two biocontrol agents, P. oligandrum and P. periplocum, and three of the RXLR genes were found to induce a defense response in Nicotiana benthamiana. Taken together, our findings represent the first evidence of RXLR effectors in Pythium species, providing valuable information on their evolutionary patterns and the mechanisms of their interactions with diverse hosts.

[Comparison of mechanical properties of three machinable resin ceramic composite materials].

PURPOSE: This in vitro study was to compare the flexural properties, fracture toughness and hardness of three machinable composite materials. METHODS: Three kinds of resin composite ceramic Upcera Hyramic, 3M Lava Ultimate, Vita Enamic and a glass ceramic Vitablocs Mark II were chosen for the study. Bar-shaped specimens (16 mm×4 mm×1 mm, 2 mm) were prepared for flexural strength experiment; specimens (17 mm×4 mm×3 mm) were prepared for fracture toughness experiment and specimens of 4 mm thickness were prepared for hardness test. Flexural test and fracture toughness experiment were performed with an universal testing machine at a cross-head speed of 0.5 mm/min. Hardness test was performed with an micro hardness tester.Scanning electron microscope was used to observe the roughness of fracture surface. One-way variance analysis was used to determine the statistical differences with SPSS 17.0 software package. RESULTS: The mean flexural strength of the tested blocks at 1 mm thickness was Hyramic（207.7515±13.12）MPa＞Vita Enamic（182.0286±15.18）MPa＞Lava Ultimate（145.8469±8.98）MPa＞Vitablocs MarkⅡ（103.0542±18.19）MPa. The mean flexural modulus were Vitablocs MarkⅡ（49.49±5.50）GPa＞Vita Enamic（40.65±3.80）GPa＞Hyramic（14.89±2.38）GPa＞Lava Ultimate（7.09±1.24）GPa. The mean flexural strength of the tested blocks at 2 mm thickness was Hyramic（208.1986±25.07）MPa＞Lava Ultimate（172.9297±12.73）MPa＞Vitablocs MarkⅡ（158.6587±15.37） MPa＞Vita Enamic（155.3670±13.77）MPa. The mean flexural modulus were Vitablocs MarkⅡ（24.07±1.86）GPa＞Vita Enamic（19.64±0.98）GPa＞Hyramic（10.35±0.87）GPa＞Lava Ultimate（8.68±0.86）GPa. The mean fracture toughness was Vita Enamic（1.6357±0.16）MPa·m1/2＞Lava Ultimate（1.4286±0.11）MPa·m1/2>Vitablocs MarkII（1.3233±0.10）MPa·m1/2>Hyramic（1.0614±0.09）MPa·m1/2. The hardness of the experimental group was significantly lower than that of the control group. CONCLUSIONS: According to ISO 6872/2008, three kinds of machinable resin ceramic composites meet the needs of clinical strength.Hyramic showed higher flexural strength at different thickness, it is an ideal material for dental restoration. Vita Enamic has not only higher flexural strength at the thickness of 1 mm, but also good toughness, it is suitable for repair of patients that have limited occlusal space and great bite force, named occlusal veneer.