Search

Senescence is an inevitable natural life process that involves structural and functional degeneration of tissues and organs. Recently, the process of skin aging has attracted much attention. Determining a means to delay or even reverse skin aging has become a research hotspot in medical cosmetology and anti-aging. Dysfunction in the epidermis and fibroblasts and changes in the composition and content of the extracellular matrix are common pathophysiological manifestations of skin aging. Reactive oxygen species and matrix metalloproteinases play essential roles in this process. Stem cells are pluripotent cells that possess self-replication abilities and can differentiate into multiple functional cells under certain conditions. These cells also possess a strong ability to facilitate tissue repair and regeneration. Stem cell transplantation has the potential for application in anti-aging therapy. Increasing studies have demonstrated that stem cells perform functions through paracrine processes, particularly those involving exosomes. Exosomes are nano-vesicular substances secreted by stem cells that participate in cell-to-cell communication by transporting their contents into target cells. In this chapter, the biological characteristics of exosomes were reviewed, including their effects on extracellular matrix formation, epidermal cell function, fibroblast function and antioxidation. Exosomes derived from stem cells may provide a new means to reverse skin aging.

Quantum systems that undergo quantum phase transitions exhibit divergent susceptibility and can be exploited as probes to estimate physical parameters. We generalize the dynamic framework for criticality-enhanced quantum sensing by the quantum Rabi model (QRM) to its anisotropic counterpart and derive the correspondingly analytical expressions for the quantum Fisher information (QFI). We find that the contributions of the rotating-wave and counterrotating-wave interaction terms are symmetric at the limit of the infinite ratio of qubit frequency to field frequency, with the QFI reaching a maximum for the isotropic quantum Rabi model. At finite frequency scaling, we analytically derive the inverted variance of higher-order correction and find that it is more affected by the rotating-wave coupling than by the counterrotating-wave coupling.

Oral mucositis (OM) is a common complication during chemotherapy characterized by ulceration, mucosa atrophy, and necrosis, which seriously interferes with nutritional intake and oncotherapy procedures among patients. However, the efficacy of current treatments for OM remains limited. Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including antioxidant and anti-inflammatory potential. In this study, we aimed to investigate the chemopreventive effects and mechanisms of CBD in protecting C57BL/6N mice and human oral keratinocytes (HOK) from 5-fluorouracil- (5-FU-) induced OM. Here, we found that CBD alleviated the severity of 5-FU-induced OM in mice, including improved survival, decreased body weight loss, reduced ulcer sizes, and improved clinical scores. Histologically, CBD restored epithelial thickness and normal structure in tongue tissues. Meanwhile, CBD attenuated reactive oxygen species (ROS) overproduction and improved the antioxidant response, suppressed the inflammatory response, promoted the proliferation of epithelial cells, and inhibited 5-FU-induced apoptosis. In vitro, consistent outcomes showed that CBD suppressed cellular ROS levels, enhanced antioxidant ability, reduced inflammatory response, promoted proliferation, and inhibited apoptosis in 5-FU-treated HOK cells. In particular, CBD upregulated the expression levels of antioxidant enzymes, heme oxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase 1 (NQO1), by increasing the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and decreasing Kelch-like ECH-associated protein 1 (Keap1). Notably, the Nrf2 inhibitor ML385 reversed the protective effect of CBD. Nrf2-siRNA transfection also significantly blunted the antioxidant effect of CBD in in vitro OM model. Collectively, our findings suggested that CBD protected against 5-FU-induced OM injury at least partially via the Nrf2/Keap1/ARE signaling pathways, highlighting the therapeutic prospects of CBD as a novel strategy for chemotherapy-induced OM.

Chronic inflammation of bone tissue often results in bone defects and hazards to tissue repair and regeneration. Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including anti-inflammatory and osteogenic potential. This study aimed to investigate the efficacy and mechanisms of CBD in the promotion of bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation in the inflammatory microenvironment.BMSCs isolated from C57BL/6 mice, expressed stem cell characteristic surface markers and presented multidirectional differentiation potential. The CCK-8 assay was applied to evaluate the effects of CBD on BMSCs' vitality, and demonstrating the safety of CBD on BMSCs. Then, BMSCs were stimulated with lipopolysaccharide (LPS) to induce inflammatory microenvironment. We found that CBD intervention down-regulated mRNA expression levels of inflammatory cytokines and promoted cells proliferation in LPS-treated BMSCs, also reversed the protein and mRNA levels downregulation of osteogenic markers caused by LPS treatment. Moreover, CBD intervention activated the cannabinoid receptor 2 (CB2) and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. While AM630, a selective CB2 inhibitor, reduced phosphorylated (p)-p38 levels. In addition, AM630 and SB530689, a selective p38 MAPK inhibitor, attenuated the enhancement of osteogenic markers expression levels by CBD in inflammatory microenvironment, respectively.CBD promoted osteogenic differentiation of BMSCs via the CB2/p38 MAPK signaling pathway in the inflammatory microenvironment.

ImportanceThe Sabin-strain inactivated poliovirus vaccine (IPV) may be a tool for polio outbreak response in certain situations.ObjectiveTo investigate the response to a type 2 vaccine-derived poliovirus (VDPV2) outbreak.Design, Setting, and ParticipantsThis case series was conducted in China after a VDPV2 was detected in stool specimens from a child with acute flaccid paralysis (AFP) in Sichuan Province in 2019, 3 years after the global withdrawal of live, attenuated type 2 oral poliovirus vaccine (OPV). Investigation followed National Health Commission and World Health Organization guidance and included searching hospitals for unreported AFP cases; testing stool specimens from the child, his contacts, and local children; enhanced environmental surveillance for VDPV2s in wastewater; and measuring vaccination coverage. Sabin-strain IPV campaigns were conducted in a wide geographic area.Main Outcomes and MeasuresAny VDPV2 detection after completion of the supplementary immunization activities.ResultsA 28-nucleotide-change VDPV2 was isolated from a young boy. Three VDPV2s were detected in healthy children; 2 were contacts of the original child, and none had paralysis. A search of 31 million hospital records found 10 unreported AFP cases; none were polio. No type 2 polioviruses were found in wastewater. Prior to the event, polio vaccine coverage was 65% among children younger than 5 years. Sabin-strain IPV campaigns reached more than 97% of targeted children, administering 1.4 million doses. No transmission source was identified. More than 1 year of enhanced poliovirus environmental and AFP surveillance detected no additional VDPVs.Conclusions and RelevanceThese findings suggest that the circulating VPDV2 outbreak in 2019 was associated with low vaccine coverage. An investigation discovered 3 infected but otherwise healthy children and no evidence of the virus in wastewater. Following Sabin-strain IPV–only campaigns expanding from county to prefecture, the poliovirus was not detected, and the outbreak response was considered by an expert panel and the World Health Organization to have been successful. This success suggests that the Sabin-strain IPV may be a useful tool for responding to circulating VDPV2 outbreaks when high-quality supplementary immunization activities can be conducted and carefully monitored in settings with good sanitation.

We present a high-energy, hundred-picosecond (ps) pulsed mid-ultraviolet solid-state laser at 266 nm by a direct second harmonic generation (SHG) in a barium borate (BaB2O4, BBO) nonlinear crystal. The green pump source is a 710 mJ, 330 ps pulsed laser at a wavelength of 532 nm with a repetition rate of 1 Hz. Under a green pump energy of 710 mJ, a maximum output energy of 253.3 mJ at 266 nm is achieved with 250 ps pulse duration resulting in a peak power of more than 1 GW, corresponding to an SHG conversion efficiency of 35.7% from 532 to 266 nm. The experimental data were well consistent with the theoretical prediction. To the best of our knowledge, this laser exhibits both the highest output energy and highest peak power ever achieved in a hundred-ps/ps regime at 266 nm for BBO-SHG.

Oral poliovirus vaccine (OPV) has proven to be highly effective in the global effort to eradicate poliomyelitis because of its ability to induce both humoral and intestinal immunity, ease of administration, and low cost (1). Sabin-strain OPV contains live attenuated virus and induces immunity by replicating in the intestinal tract, triggering an immune response that clears the vaccine virus. However, among undervaccinated communities and persons with immunodeficiency, OPV mutations that arise during prolonged replication can result in the emergence of genetically divergent, neurovirulent vaccine-derived polioviruses (VDPVs). In addition, OPV has resulted in rare cases of vaccine-associated paralytic poliomyelitis (VAPP) among vaccine recipients or their close contacts (1). Identification of circulating polioviruses relies on surveillance of acute flaccid paralysis (AFP) and environmental surveillance of wastewater (i.e., sewage). In 2022, type 3 VDPV (VDPV3) was detected in stool specimens from an infant with primary immunodeficiency disorder (PID) through a pilot surveillance program to identify VDPVs in children with PIDs. Integrated AFP, environmental, and immunodeficiency-associated VDPV (iVDPV) surveillance is critical to detecting and containing all polioviruses and achieving the goal of global polio eradication.

Taiwan faces challenges in providing long-term family care as its population rapidly ages. This study aimed to construct a health application that could effectively meet family caregivers' needs in providing home care. Mixed methods were adopted to explore their acceptance of the application, as well as to gather their suggestions for improving the application. A nonrandomized controlled group pretest-posttest design was utilized. The participants were family caregivers who were recruited via purposive sampling at a regional hospital in Taipei, Taiwan. The caregivers used the application to monitor and manage the health of those they were caring for. Elderly family caregivers scored 1.57 and 1.16 points higher than their middle-aged counterparts in terms of performance expectancy (0.61-2.53, P = .01) and effort expectancy (0.25-2.06, P = .01), respectively. The caregivers opined that it was convenient to use the application for managing the health data of their patients, and resources and solutions for overcoming problems when using the application were easily within their reach. They also suggested that relevant information for promoting patient mental health could also be included in the application. Thus, the software is acceptable to all the family caregivers regardless of age, indicating that it can assist family caregivers in the future in performing home care management.

Background With the development of instrument technology, the functions and detection methods of automatic blood cell analyzers have become more complex. To ensure optimal clinical applicability, it is crucial to select an automatic blood cell analyzer with excellent clinical detection performance. This study evaluated the latest Mindray BC-6800Plus automatic blood cell analyzer and assessed its performance in the detection of nucleated red blood cells (NRBCs). Methods A total of 490 clinical blood samples were used to assess the performance of the instrument, including parameters such as precision, linearity, conformity rate of manual microscopic examination, carryover, and limit of quantitation. Results The instrument showed a small carryover (≤0.02) and excellent linearity (R2≥0.9986). The reproducibility of the sample tests was satisfactory, and the coefficient of variation (CV) of the test results [0.98-1.72% and 0.62-6.97% for white blood cells (WBCs) and NRBCs, respectively] were significantly lower than that declared by the manufacturer (2.5% and 20% for WBCs and NRBCs, respectively). Thus, the BC-6800Plus satisfies the requirements of clinical testing. Two separate Mindray BC-6800Plus machines were tested and found to be in good agreement with each other and with manual microscopy methods. Furthermore, WBC and NRBC counts were highly consistent with results obtained using the XN-9100 blood analyzer. Conclusions The Mindray BC-6800Plus is an excellent analyzer that can provide timely and accurate reports for clinical laboratory detection of NRBC.

Background: A high mortality rate makes hepatocellular carcinoma (HCC) one of the most common types of cancer globally. 5-methylcytosine (m5C) is an epigenetic modification that contributes to the prognosis of several cancers, but its relevance to HCC remains unknown. We sought to determine if the m5C-related regulators had any diagnostic or prognostic value in HCC.Methods: M5C regulatory genes were screened and compared between HCC and normal tissue from The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases. Least absolute shrinkage and selection operator method (LASSO) and univariate Cox regression analysis of differentially expressed genes were then performed to identify diagnostic markers. A LASSO prognostic model was constructed using M5C regulatory genes with prognostic values screened by TCGA expression data. HCC patients were stratified based on risk score, then clinical characteristics analysis and immune correlation analysis were performed for each subgroup, and the molecular functions of different subgroups were analyzed using both Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA). The prognostic model was evaluated using univariate and multivariate Cox analyses as well as a nomogram. Molecular typing was performed according to m5C regulatory genes and immune checkpoint genes expression respectively, and clinical characterization and immune correlation analysis were performed for each subgroup.Results: M5C regulatory genes are expressed differently in HCC patients with different clinical and pathological characteristics, and mutations in these genes are frequent. Based on five m5C regulators (NOP2, NSUN2, TET1, YBX1, and DNMT3B), we constructed a prognostic model with high predictive ability. The risk score was found to be an independent prognostic indicator. Additionally, risk scores can also be applied in subgroups with different clinical characteristics as prognostic indicators.Conclusion: The study combined data from TCGA and GEO for the first time to reveal the genetic and prognostic significance of m5C-related regulators in HCC, which provides new directions for identifying predictive biomarkers and developing molecularly targeted therapies for HCC.

Gold nanoparticles (AuNPs) have been shown to enhance cancer radiotherapy (RT) gain by localizing the absorption of radiation energy in the tumor while sparing surrounding normal tissue from radiation toxicity. Previously, we showed that AuNPs enhanced RT induced DNA damage and cytotoxicity in MCF7 breast cancer cells. Interestingly, we found that cancer cells exhibited a size-dependent AuNPs intracellular localization (4 nm preferentially in the cytoplasm and 14 nm in the nucleus). We extended those studies to an in vivo model and examined the AuNPs effects on RT cytotoxicity, survival and immunomodulation of tumor microenvironment (TME) in human triple negative breast cancer (TNBC) xenograft mouse model. We also explored the significance of nanoparticle size in these AuNPs’ effects. Mice treated with RT and RT plus 4 nm or 14 nm AuNPs showed a significant tumor growth delay, compared to untreated animals, while dual RT plus AuNPs treatment exhibited additive effect compared to either RT or AuNPs treatment alone. Survival log-rank test showed significant RT enhancement with 14 nm AuNP alone; however, 4 nm AuNPs did not exhibit RT enhancement. Both sizes of AuNPs enhanced RT induced immunogenic cell death (ICD) that was coupled with significant macrophage infiltration in mice pretreated with 14 nm AuNPs. These results showing significant AuNP size-dependent RT enhancement, as evident by both tumor growth delay and overall survival, reveal additional underlying immunological mechanisms and provide a platform for studying RT multimodal approaches for TNBC that may be combined with immunotherapies, enhancing their effect.

By using superaligned carbon nanotube (SACNT) macrostructures as reinforcements, the one-step homoepitaxial growth of SACNT/graphite composites was achieved with a home-built experimental setup at temperatures as high as 2600 °C. Compared with traditional furnace heating method, this approach offers the advantages of increased convenience, high throughput and energy efficiency. This high-temperature homoepitaxy strategy was applied to three kinds of structures: SACNT yarn, SACNT film, and SACNT array. Because of the high temperature which exceeded 1800 °C, the samples after high-temperature homoepitaxy showed increased G/D peak area ratios in the Raman spectra, enhanced mechanical properties and improved thermal properties, all of which can meet the requirements of various applications.

Purpose To investigate the differences between internal target volumes (ITVs) contoured on the simulation 4DCT and daily 4DCBCT images for lung cancer patients treated with stereotactic body radiotherapy (SBRT) and determine the dose delivered on 4D planning technique. Methods For nine patients, 4DCBCTs were acquired before each fraction to assess tumor motion. An ITV was contoured on each phase of the 4DCBCT and a union of the 10 ITVs was used to create a composite ITV. Another ITV was drawn on the average 3DCBCT (avgCBCT) to compare with current clinical practice. The Dice coefficient, Hausdorff distance, and center of mass (COM) were averaged over four fractions to compare the ITVs contoured on the 4DCT, avgCBCT, and 4DCBCT for each patient. Planning was done on the average CT, and using the online registration, plans were calculated on each phase of the 4DCBCT and on the avgCBCT. Plan dose calculations were tested by measuring ion chamber dose in the CIRS lung phantom. Results The Dice coefficients were similar for all three comparisons: avgCBCT‐to‐4DCBCT (0.7 ± 0.1), 4DCT‐to‐avgCBCT (0.7 ± 0.1), and 4DCT‐to‐4DCBCT (0.7 ± 0.1); while the mean COM differences were also comparable (2.6 ± 2.2mm, 2.3 ± 1.4mm, and 3.1 ± 1.1mm, respectively). The Hausdorff distances for the comparisons with 4DCBCT (8.2 ± 2.9mm and 8.1 ± 3.2mm) were larger than the comparison without (6.5 ± 2.5mm). The differences in ITV D95% between the treatment plan and avgCBCT calculations were 4.3 ± 3.0% and −0.5 ± 4.6%, between treatment plan and 4DCBCT plans, respectively, while the ITV V100% coverages were 99.0 ± 1.9% and 93.1 ± 8.0% for avgCBCT and 4DCBCT, respectively. Conclusion There is great potential for 4DCBCT to evaluate the extent of tumor motion before treatment, but image quality challenges the clinician to consistently delineate lung target volumes.

Actively tunable acoustic metamaterials have attracted ever increasing attention. However, their tunable frequency range is quite narrow (tens of Hz) even under ultrahigh applied voltage (about 1,000 V). Here, we report a superbroad-band actively tunable acoustic metamaterials with the bandwidth over 400 Hz under a low voltage. In the actively tunable acoustic metamaterials, the acoustic membrane is a laminated nanocomposite consisting of a poly (ethylene terephthalate) (PET) and super-aligned carbon nanotube (CNT) drawn from CNT forest array. The laminated nanocomposite membrane exhibits adjustable acoustic properties, whose modulus can be adjusted by applying external electric field. The maximum frequency bandwidth of PET/CNT nanocomposite membrane reaches 419 Hz when applying an external DC voltage of 60 V. Our actively tunable acoustic metamaterials with superbroad-band and lightweight show very promising foreground in noise reduction applications.

Purpose To perform radiomic analysis of primary tumors extracted from pretreatment contrast-enhanced computed tomography (CE-CT) images for patients with oropharyngeal cancers to identify discriminant features and construct an optimal classifier for the characterization and prediction of human papilloma virus (HPV) status. Materials and methods One hundred and eighty seven patients with oropharyngeal cancers with known HPV status (confirmed by immunohistochemistry-p16 protein testing) were retrospectively studied as follows: Group A: 95 patients (19HPV- and 76HPV+) from the MICAII grand challenge. Group B: 92 patients (52HPV- and 40HPV+) from our institution. Radiomic features (172) were extracted from pretreatment diagnostic CE-CT images of the gross tumor volume (GTV). Levene and Kolmogorov-Smirnov's tests with absolute biserial correlation (>0.48) were used to identify the discriminant features between the HPV+ and HPV- groups. The discriminant features were used to train and test eight different classifiers. Area under receiver operating characteristic (AUC), positive predictive and negative predictive values (PPV and NPV, respectively) were used to evaluate the performance of the classifiers. Principal component analysis (PCA) was applied on the discriminant feature set and seven PCs were used to train and test a generalized linear model (GLM) classifier. Results Among 172 radiomic features only 12 radiomic features (from 3 categories) were significantly different (P 0.48) between the HPV+ and HPV- groups. Among the eight classifiers trained and applied for prediction of HPV status, the GLM showed the highest performance for each discriminant feature and the combined 12 features: AUC/PPV/NPV = 0.878/0.834/0.811. The GLM high prediction power was AUC/PPV/NPV = 0.849/0.731/0.788 and AUC/PPV/NPV = 0.869/0.807/0.870 for unseen test datasets for groups A and B, respectively. After eliminating the correlation among discriminant features by applying PCA analysis, the performance of the GLM was improved by 3.3%, 2.2%, and 1.8% for AUC, PPV, and NPV, respectively. Conclusions Results imply that GTV's for HPV+ patients exhibit higher intensities, smaller lesion size, greater sphericity/roundness, and higher spatial intensity-variation/heterogeneity. Results are suggestive that radiomic features primarily associated with the spatial arrangement and morphological appearance of the tumor on contrast-enhanced diagnostic CT datasets may be potentially used for classification of HPV status.

What is already known about this topic? After the type 2 strain of the live, attenuated poliovirus vaccine was withdrawn globally in 2016, any identification of a type 2 poliovirus is a Public Health Emergency of International Concern. A vaccine-derived type 2 poliovirus (VDPV2) was identified in Sichuan, prompting an urgent, comprehensive investigation and response. What is added by this report? Type 2 monovalent, live, attenuated oral poliovirus vaccine (mOPV2) is being used to respond to the numerous VDPV2 outbreaks seen around the world. In contrast, the response in Sichuan used Sabin strain inactivated poliovirus (sIPV) to stop circulation of the VDPV2. In the 6 months following the vaccination response, there have been no VDPV2s detected in Sichuan, despite extensive search. What are the implications for public health practices? Further search for the VDPV2 must continue in order to determine whether transmission has been stopped. The ongoing investigation and response to the Sichuan VDPV2 is providing evidence to the Global Polio Eradication Initiative on managing VDPV2 outbreaks.

Seawater electrolysis not only affords a promising approach to produce clean hydrogen fuel but also alleviates the bottleneck of freshwater feeds. Here, a novel strategy for large-scale preparing spinel Ni

Evaluate custom beam models for a second check dose calculation system using statistically verifiable passing criteria for film analysis, DVH, and 3D gamma metrics.Custom beam models for nine linear accelerators for the Sun Nuclear Dose Calculator algorithm (SDC, Sun Nuclear) were evaluated using the AAPM-TG119 test suite (5 Intensity Modulated Radiation Therapy (IMRT) and 5 Volumetric Modulated Arc Therapy (VMAT) plans) and a set of clinical plans. Where deemed necessary, adjustments to Multileaf Collimator (MLC) parameters were made to improve results. Comparisons to the Analytic Anisotropic Algorithm (AAA), and gafchromic film measurements were performed. Confidence intervals were set to 95% per TG-119. Film gamma criteria were 3%/3 mm (conventional beams) or 3%/1 mm (Stereotactic Radiosurgery [SRS] beams). Dose distributions in solid water phantom were evaluated based on DVH metrics (e.g., D95, V20) and 3D gamma criteria (3%/3 mm or 3%/1 mm). Film passing rates, 3D gamma passing rates, and DVH metrics were reported for HD MLC machines and Millennium MLC Machines.For HD MLC machines, SDC gamma film agreement was 98.76% ± 2.30% (5.74% CL) for 6FFF/6srs (3%/1 mm), and 99.80% ± 0.32% (0.83% CL) for 6x (3%/3 mm). For Millennium MLC machines, film passing rates were 98.20% ± 3.14% (7.96% CL), 99.52% ± 1.14% (2.71% CL), and 99.69% ± 0.82% (1.91% CL) for 6FFF, 6x, and 10x, respectively. For SDC to AAA comparisons: HD MLC Linear Accelerators (LINACs); DVH point agreement was 0.97% ± 1.64% (4.18% CL) and 1.05% ± 2.12% (5.20% CL); 3D gamma agreement was 99.97% ± 0.14% (0.30% CL) and 100.00% ± 0.02% (0.05% CL), for 6FFF/6srs and 6x, respectively; Millennium MLC LINACs: DVH point agreement was 0.77% ± 2.40% (5.47% CL), 0.80% ± 3.40% (7.47% CL), and 0.07% ± 2.15% (4.30% CL); 3D gamma agreement was 99.97% ± 0.13% (0.29% CL), 99.97% ± 0.17% (0.36% CL), and 99.99% ± 0.06% (0.12% CL) for 6FFF, 6x, and 10x, respectively.SDC shows agreement well within TG119 CLs for film and redundant dose calculation comparisons with AAA. In some models (SRS), this was achieved using stricter criteria. TG119 plans can be used to help guide model adjustments and to establish clinical baselines for DVH and 3D gamma criteria.

The main progress of generating all-solid-state deep ultraviolet (DUV) and vacuum ultraviolet (VUV) lasers with KBe2BO3F2 (KBBF) crystal is reviewed.

Superradiant phase transitions (SPTs) are important for understanding light-matter interactions at the quantum level [1, 2], and play a central role in criticality-enhanced quantum sensing [3]. So far, SPTs have been observed in driven-dissipative systems [4-9], but the emergent light fields did not show any nonclassical characteristic due to the presence of strong dissipation. Here we report an experimental demonstration of the SPT featuring the emergence of a highly nonclassical photonic field, realized with a resonator coupled to a superconducting qubit, implementing the quantum Rabi model [10, 11]. We fully characterize the light-matter state by Wigner matrix tomography. The measured matrix elements exhibit quantum interference intrinsic of a photonic Schrödinger cat state [12], and reveal light-matter entanglement. Besides their fundamental importance, these hitherto unobserved emergent quantum phenomena are useful for quantum metrology and fault-tolerant quantum computation., 19 pages, 14 figures, 2 tables

Additional file 1. Supplemental material 1.

Directional solidification equipment is an efficient purification tool. In this paper, the geometric model was established based on the equipment, and the numerical simulation of the flow field in equipment was realized through the RNG turbulence model, flow volume function model, and the multiple reference system method. In order to improve the fluid velocity, turbulent kinetic energy, and uniform distribution of circulating flow in the flow field, the effects of different crucible structures, process parameters, and structure of rotator on the flow field were analyzed. The research results show that the round bottom crucible has a faster flow velocity in front of the wall, and the flow velocity distribution is uniform. When the rotator is located in the center of the flow field, flow velocity and turbulent kinetic energy are distributed more evenly. Controlling the rotational speed to reduce the air entering the liquid phase is conducive to preventing solidification from being oxidized. Considering the thickness of the solidified layer, increasing the blade length can help increase the fluid velocity.

Objectives. In this study, a new type of dental implant by covering the surface of the titanium (Ti) implant with zinc-magnesium (Zn-Mg) alloy was designed, to study the antibacterial and antioxidant effects of Mg alloy on titanium (Ti) implants in oral implant restoration. Methods. Human gingival fibroblasts (HGFs), S. sanguinis, and F. nucleatum bacteria were used to detect the bioactivity and antibacterial properties of Mg alloy-coated Ti implants. In addition, B6/J mice implanted with different materials were used to further detect their antibacterial and antioxidant properties. Results. The results showed that Mg alloy could better promote the adhesion and proliferation and improve the alkaline phosphatase (ALP) activity of HGFs, which contributed to better improved stability of implant osseointegration. In addition, Mg alloy could better inhibit the proliferation of S. sanguinis, while no significant difference was found in the proliferation of F. nucleatum between the two implants. In the mouse model, the peripheral inflammatory reaction and oxidative stress of the Mg alloy implant were significantly lower than those of the Ti alloy implant. Conclusions. Zn-Mg alloy-coated Ti implants could better inhibit the growth of Gram-positive bacteria in the oral cavity, inhibit oxidative stress, and facilitate the proliferation activity of HGFs and the potential of osteoblast differentiation, thus, better increasing the stability of implant osseointegration.

Salivary adenoid cystic carcinoma (SACC), one of the most common malignant tumors in the head and neck region, is characterized by high postoperative recurrence rate and poor prognosis. Microwave (MW) ablation possesses advantages in preserving SACC patients' facial aesthetics and oral function, but unfortunately, it suffers from low therapeutic efficacy due to the limited MW-thermal efficiency. Moreover, the insufficient thermal ablation may aggravate hypoxic state in tumors, which is deleterious to the treatment of residual tumors and aggressive tumors. Hence, MW ablation has been rarely applied in treating head and neck tumors in recent years. To minimize the unfavorable outcomes and maximize the therapeutic effects of MW ablation, a MW sensitizer coupled with a self-sufficient oxygen nanoagent was employed for the first time in MW ablation to treat head and neck tumors. We prepared a graphene-containing metal-organic framework (ZIF67@Gr-PEG), which exhibited excellent MW thermal conversion ability endowed by the incorporated Gr and showed

Reinforcement learning takes sequential decision-making approaches by learning the policy through trial and error based on interaction with the environment. Combining deep learning and reinforcement learning can empower the agent to learn the interactions and the distribution of rewards from state-action pairs to achieve effective and efficient solutions in more complex and dynamic environments. Deep reinforcement learning (DRL) has demonstrated astonishing performance in surpassing the human-level performance in the game domain and many other simulated environments. This paper introduces the basics of reinforcement learning and reviews various categories of DRL algorithms and DRL models developed for medical image analysis and radiation treatment planning optimization. We will also discuss the current challenges of DRL and approaches proposed to make DRL more generalizable and robust in a real-world environment. DRL algorithms, by fostering the designs of the reward function, agents interactions and environment models, can resolve the challenges from scarce and heterogeneous annotated medical image data, which has been a major obstacle to implementing deep learning models in the clinic. DRL is an active research area with enormous potential to improve deep learning applications in medical imaging and radiation therapy planning.

Background: Clinical drugs for herpesvirus exhibit high toxicity and suffer from significant drug resistance. The development of new, effective, and safe anti-herpesvirus agents with different mechanisms of action is greatly required. Objective: Novel inhibitors against herpesvirus with different mechanisms of action from that of clinical drugs. Methods: A series of novel 5-(benzylamino)-1H-1,2,3-triazole-4-carboxamides were efficiently synthesized and EC50 values against Human Cytomegalovirus (HCMV), Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV) were evaluated in vitro. Results: Some compounds present antiviral activity. Compounds 5s and 5t are potent against both HCMV and VZV. Compounds 5m, 5n, 5s, and 5t show similar EC50 values against both TK+ and TK− VZV strains. Conclusion: 5-(Benzylamino)-1H-1, 2,3-triazole-4-carboxamides are active against herpesviruses and their activity is remarkably affected by the nature and the position of substituents in the benzene ring. The results indicate that these derivatives are independent of the viral thymidine kinase (TK) for activation, which is indispensable for current drugs. Their mechanisms of action may differ from those of the clinic anti-herpesvirus drugs.

Background Measles is among the most highly infectious human diseases. By virtue of increasingly effective childhood vaccination, together with targeted supplemental immunization activities (SIAs), health authorities in the People’s Republic of China have reduced measles’ reproduction number from about 18 to 2.3. Despite substantial residual susceptibility among young adults, more in some locales than others, sustained routine childhood immunization likely would eliminate measles eventually. To support global eradication efforts, as well as expedite morbidity and mortality reductions in China, we evaluated alternative SIAs via mechanistic mathematical modelling. Methods Our model Chinese population is stratified by immune status (susceptible to measles infection; infected, but not yet infectious; infectious; and recovered or immunized), age (0, 1–4, 5–9, …, 65+ years) and location (31 provinces). Contacts between sub-populations are either empirical or a mixture of preferential and proportionate with respect to age and decline exponentially with distance between locations at age-dependent rates. We estimated initial conditions and most parameters from recent cross-sectional serological surveys, disease surveillance and demographic observations. Then we calculated the reproduction numbers and gradient of the effective number with respect to age- and location-specific immunization rates. We corroborated these analytical results by simulating adolescent and young adult SIAs using a version of our model in which the age-specific contact rates vary seasonally. Results Whereas the gradient indicates that vaccinating young adults generally is the optimal strategy, simulations indicate that a catch-up campaign among susceptible adolescent schoolchildren would accelerate elimination, with timing dependent on uptake. Conclusions These results are largely due to indirect effects (i.e. fewer infections than immunized people might otherwise cause), which meta-population models with realistic mixing are uniquely capable of reproducing accurately.

The treatment of articular cartilage defects has become a major clinical concern. Currently, additional efforts are necessary to develop effective methods to cure this disease. In this work, we combined gene therapy with tissue engineering methods to test their effect on cartilage repair. In in vitro experiments, we obtained C-type natriuretic peptide (CNP) gene-modified bone marrow-derived mesenchymal stem cells (BMSCs) by transfection with recombinant adenovirus containing the CNP gene and revealed that CNP gene-modified BMSCs had good chondrogenic differentiation ability. By the freeze-drying method, we successfully synthesized a chitosan/silk fibroin (CS/SF) porous scaffold, which had a suitable aperture size for chondrogenesis. Then, we loaded CNP gene-modified BMSCs onto CS/SF scaffolds and tested their effect on repairing full-thickness cartilage defects in rat joints. The gross morphology and histology examination results showed that the composite of the CNP gene-modified BMSCs and CS/SF scaffolds had better repair effects than those of the other three groups at each time point. Additionally, compared to the group with BMSCs and scaffolds, we found that there was more cartilage matrix in the CNP gene-modified BMSCs and CS/SF scaffolds group. Data obtained in the present study suggest that the composite of CNP gene-modified BMSCs and CS/SF scaffolds represent promising strategies for repairing focal cartilage lesions.

To evaluate the feasibility and safety of reproductive organ preserving radical cystectomy (ROPRC) compared to radical cystectomy (RC) for elderly female patients with muscle-invasive bladder cancer.We retrospectively studied 135 elderly female patients (aged ≥75 years) who underwent RC followed by cutaneous ureterostomies at our center between January 1, 2007 and December 31, 2017. Eighty-four patients treated with RC, and 51 patients treated with ROPRC, were grouped into 45 pairs. Patient demographics, extensive peri-operative, and oncological data were then recorded and evaluated.In the matched group, the incidence of short-term and long-term complications in the ROPRC group were lower than the RC group (18.0% vs 28.0%, P = .035; 12.0% vs 22.0%, P = .030). Furthermore, operative time was shorter, estimated blood loss was lower, and bowel recovery was quicker in the ROPRC group (207.5 minutes vs 267.9 minutes, P.001; 500 mL vs 600 mL, P = .024; 3.0 days vs 4.0 days, P.001, respectively) compared to the RC group. The recurrence free survival (P = .658), overall survival (P = .604), and cancer-specific survival (P = .361) were all equivalent when compared between the 2 groups with a median follow-up period of 34.0 and 38.0 months, respectively. The surgical approach (RC vs ROPRC) was an independent risk factor for short-term complications (P = .045), duration of operative time (P.001), estimated blood loss (P = .004), and bowel recovery (P.001).This propensity score-matched cohort study showed that ROPRC was both feasible and safe for elderly female patients with muscle-invasive bladder cancer compared to RC, and also had comparable oncological outcomes after a lengthy follow-up period.

The authors of this meta-analysis evaluated whether there is a difference in the levels of serum and gingival crevicular fluid (GCF) matrix metalloproteinase (MMP)-9 between patients with periodontitis and periodontally healthy control participants.The authors searched PubMed, Embase, the Cochrane Library, and the China Biology Medicine disk databases for eligible studies in which the investigators reported the relationships between MMP-9 levels in serum and GCF and periodontitis. The authors pooled the standardized mean differences (SMDs) and 95% confidence intervals (CIs) from each study to evaluate the difference in the serum and GCF MMP-9 levels between patients with periodontitis and periodontally healthy control participants.Results of a meta-analysis of 6 case-control studies including a total of 923 healthy control participants and 557 patients with periodontitis indicated that serum MMP-9 levels were significantly higher in patients with periodontitis than in periodontally healthy control participants (SMD, 1.60; 95% CI, 0.17 to 3.03; P.05). Results of a separate meta-analysis of 6 case-control studies including a total of 153 healthy control participants and 189 patients with periodontitis indicated that GCF MMP-9 levels were significantly higher in patients with periodontitis than in periodontally healthy control participants (SMD, 1.96; 95% CI, 0.76 to 3.16; P.01).The results of the meta-analysis revealed statistically significant differences in the MMP-9 levels in serum and GCF between patients with periodontitis and periodontally healthy control participants. These results cannot be used to confirm causality because the included studies were all case-control studies in which the investigators reported associations. Moreover, readers should view the results with caution because of the considerable heterogeneity among the studies included in the meta-analysis.

Huan-huan Wang,1,* Zhi-guang Fu,1,* Wei Li,2 Yun-xia Li,1 Li-sheng Zhao,1 Li Wen,1 Jian-jun Zhang,2 Ning Wen1 1Department of Stomatology, Chinese PLA General Hospital, Beijing 100853, China; 2College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, China *These authors contributed equally to this work Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies, with high rates of mortality and morbidity worldwide. Owing to the special anatomical location of this tumor, an effective, minimally invasive treatment with low systemic toxicity is highly desirable. Hydrogels have shown great potential for tumor-targeting therapy, with excellent performance. However, there have been few reports on co-loading photosensitizers and chemotherapeutic drugs into hydrogels. In this study, we synthesized a nano doxorubicin-indocyanine green matrix metalloproteinase (MMP)-responsive hydrogel (denoted as NDIMH), combining chemotherapy and phototherapy, to achieve superior antitumor efficacy.Methods: First, NDIMH was synthesized and characterized by scanning electron microscopy and drug-release assays. Second, the photosensitivity properties and antitumor efficiency of this drug delivery system were studied invivo and invitro. Last, the imaging and biodistribution of NDIMH were monitored using the Maestro EX invivo imaging system.Results: The nanodrugs loaded into the smart hydrogel exhibited uniform size distribution, excellent size stability, and a sustained release in the presence of MMP-2. NDIMH showed ideal photosensitivity characteristics under light. NDIMH with 808 nm near-infrared (NIR) irradiation effectively inhibited the viability, invasion, and metastasis of SCC-15 invitro. After intratumoral injection of NDIMH with 808 nm NIR illumination, the hydrogels exhibited favorable synergistic antitumor efficacy and acceptable biosafety. Additionally, fluorescence imaging showed that NDIMH could significantly improve the retention of nanodrugs at the tumor site.Conclusion: The intratumoral injection of NDIMH with 808 nm NIR irradiation could be a promising chemophototherapy alternative for HNSCC. Keywords: hydrogel, MMP-responsive, doxorubicin, indocyanine green, chemophototherapy

Background While PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) plays an important role in double-strand break (DSB) repair to retain genomic stability, there is still no pan-cancer analysis based on large clinical information on the relationship between PRKDC and different tumors. For the first time, this research used numerous databases to perform a pan-cancer review for PRKDC to explore the possible mechanism of PRKDC in the etiology and outcomes in various tumors. Methods PRKDC's expression profile and prognostic significance in pan-cancer were investigated based on various databases and online platforms, including TIMER2, GEPIA2, cBioPortal, CPTAC, and SangerBox. We applied the TIMER to identified the interlink of PRKDC and the immune infiltration in assorted tumors, and the SangerBox online platform was adopted to find out the relevance between PRKDC and immune checkpoint genes, TMB, and MSI in tumors. GeneMANIA tool was employed to create a Protein-Protein Interaction (PPI) analysis, gene set enrichment analysis (GSEA) was conducted to performed gene enrichment analysis. Results Overall, tumor tissue presented a higher degree of PRKDC expression than adjacent normal tissue. Meanwhile, patients with high PRKDC expression have a worse prognosis. PRKDC mutations were present in almost all TCGA tumors and might lead to a better survival prognosis. PRKDC expression level was shown a positive correlation with tumor-infiltrating immune cells (TIICs). PRKDC high expression cohorts were enriched in "cell cycle," "oocyte meiosis," and "RNA-degradation" signaling pathways. Conclusions This study revealed the potential value of PRKDC tumor immunology and as a therapeutic target and prognostic biomarker in pan-cancer.

Introduction: Research studies have already shown that tumor aggressiveness and response to chemical and radiation therapies are influenced by the extravascular extracellular space (VEES) of the tumor microenvironment. Assessment of VEES has been reported to be fundamental to understanding tumor response to treatment and probability of recurrence. Purpose: This pilot study investigates the association between wavelet-based radiomic features extracted from dynamic contrast-enhanced magnetic resonance images (DCE-MRI) of rat brain tumors against VEES estimated by pharmacokinetic modeling. Methods: Eight immune-compromised-RNU/RNU rats were implanted with human U251n cancer cells to form an orthotopic glioma (IACUC #1509). For each rat, two DCE-MRI studies (multi slice/echo GE, 3 slice(2mm),128x64, FOV:32x32mm2, TR/(TE1-TE2)=24ms/(2ms-4ms), flip angle=18º, 400 acquisitions, 1.55 sec interval, Magnevist was injected at acquisition no. 15) were performed (24h apart) using a 7T Varian (Agilent, 20cm bore) scanner. A single 20Gy stereotactic radiation exposure was performed before the second study. The post treatment MRIs were taken a range of 1-6.5 hrs post radiation. The time trace of relaxivity change (ΔR1) in all the voxels of the animal’s brain for all studies were calculated. Wavelet decomposition analysis was performed on the ΔR1 for each voxel and frequency-based localized approximations with 4 degrees of regularities were estimated. The VEES map was estimated from ΔR1 by the pharmacokinetic (modified Toft’s) model and a nested model selection technique. Finally, the Pearson correlation coefficients between the VEES map and corresponding wavelet coefficient maps in the tumor region were calculated. Results: The average voxel-wise Pearson correlation coefficients between the VEES maps (averaged for all animals) and their corresponding wavelet-based, radiomics coefficient maps were: r= -0.680, r= -0.802, r= -0.813, and r= -0.791 with p Discussion & Conclusion: This pilot study suggests that wavelet based radiomic analysis has potential to provide information pertinent to the tumor microenvironment, which correlates well with pharmacokinetic modeling. As such, this work represents an important first step toward potentially connecting radiomics with underlying biological mechanisms. Citation Format: Hassan Bagher-Ebadian, Stephen L. Brown, Olivia Valadie, Julian A. Rey, Ning Wen, Malisa Sarntinoranont, James R. Ewing, Indrin J. Chetty. Characterization of extravascular extracellular space of rat brain tumors using wavelet-based radiomics analysis of dynamic contrast enhanced MRI [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 543.

Oral squamous cell carcinoma (OSCC) can be characterized by severe functional impairment and a poor prognosis. The epidermal growth factor receptor (EGFR) is highly expressed in OSCC and is a promising target for cancer therapy. In addition, aminolevulinic acid-induced photodynamic therapy (ALA-PDT) has produced robust clinical effects in oral cancer. Here, an EGFR inhibitor, nimotuzumab, was administered to 2 OSCC cell lines, CAL-27 and SCC-25, treated with ALA-PDT. Cell growth, apoptosis, and reactive oxygen species (ROS) generation were used to measure the antitumor activity of the combination therapy. The in vivo effect of nimotuzumab plus ALA-PDT was done using a mouse OSCC xenograft model (SCC-25). EGFR expression was further compared by Western blotting in different groups. We observed that nimotuzumab combined with ALA-PDT could enhance inhibition of OSCC cell growth in vitro and in vivo. We also observed an enhanced effect after combination on cell apoptosis in CAL-27 and SCC-25 cells. Furthermore, combined therapy significantly reduced the protein expression levels of EGFR in vitro. However, we observed that nimotuzumab plus ALA-PDT did not increase ROS generation substantially in OSCC cells compared to the ALA-PDT group alone. These observations indicate that nimotuzumab combined with ALA-PDT has valuable applications for OSCC treatment.

A web-based self-health management system-eAsthmaCare, was developed as an intervention for asthmatic children. A randomized controlled trial was performed. Consent was obtained for 98 children with asthma to participate in the study and the pre- and post-test data collection process. The experimental group was given access to eAsthmaCare online management, the control group was subjected to general asthma management. The experimental and control groups' asthma symptoms, Childhood Asthma Control Test (C-ACT) scores, and lung function were evaluated, and their pre- and 3-month post-test results were compared. The following records were maintained: (1) medication record (2) daily asthma symptoms log (3) monthly C-ACT and lung function records. The C-ACT results indicated a p-value of.01 for: overall improvements to childhood asthma symptoms, time effect, group and time interaction effects, and group and time interaction effects in relation to sleeping condition on the previous day; cough symptom time effect, and group and time interaction effects; the two groups' time effect in relation to cough symptoms; the two groups' time effect in relation to monthly activity restrictions (number of days); and the two groups' time effect in relation to nasal symptoms; the two groups' time effect; and group and time interaction effects (p.01). In terms of the predictive values for lung function (FVC, FEV1, PEFR), the improvements in both groups were not statistically significant. The implementation of the eAsthmaCare intervention might have a positive impact on pediatric patients, making it an effective management tool for monitoring asthmatic children's physical function and discomfort.