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Surface plasmonics with its unique confinement of light

The craniovertebral junction (CVJ) is an anatomically complex region of the axial skeleton that provides protection of the brainstem and the upper cervical spinal cord. Structural malformation of the CVJ gives rise to life-threatening neurological deficits, such as quadriplegia and dyspnea. Unfortunately, genetic studies on human subjects with CVJ malformation are limited and the pathogenesis remains largely elusive. In this study, we recruited 93 individuals with CVJ malformation and performed exome sequencing. Manual interpretation of the data identified three pathogenic variants in genes associated with Mendelian diseases, including CSNK2A1, MSX2, and DDX3X. In addition, the contribution of copy number variations (CNVs) to CVJ malformation was investigated and three pathogenic CNVs were identified in three affected individuals. To further dissect the complex mutational architecture of CVJ malformation, we performed a gene-based rare variant association analysis utilizing 4371 in-house exomes as control. Rare variants in LGI4 (carrier rate = 3.26%, p = 3.3 × 10

Aging is characterized by a progressive deterioration of physiological integrity, leading to impaired functional ability and ultimately increased susceptibility to death. It is a major risk factor for chronic human diseases, including cardiovascular disease, diabetes, neurological degeneration, and cancer. Therefore, the growing emphasis on "healthy aging" raises a series of important questions in life and social sciences. In recent years, there has been unprecedented progress in aging research, particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes. In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases, we review the descriptive, conceptual, and interventive aspects of the landscape of aging composed of a number of layers at the cellular, tissue, organ, organ system, and organismal levels.

Electrical stimulation of the right median nerve can aid coma arousal after traumatic brain injury (TBI). This study aimed to confirm the efficacy further and explore possible mechanisms of right median nerve electrical stimulation (RMNS). Five comatose patients after severe TBI from May to September 2020 in the Tianjin Medical University General Hospital received RMNS for 2 weeks besides standard management. After the 2-week treatment, the mean Glasgow Coma Scale (GCS) and neurophysiological examination were used. We then investigated the alterations in microRNA (miRNA) expression in cerebrospinal fluid (CSF) by high-throughput whole transcriptome sequencing, analyzed the data by Gene Ontology (GO) and pathway analysis, and constructed the miRNA-target gene network. Patient awareness and brain function showed a more rapid increase after treatment. We also found 38 differently expressed miRNAs, 34 of which were upregulated and 4 downregulated. GO analysis showed a relation of these differentially expressed miRNAs with neuronal growth, repair, and neural signal transmission. The most highly correlated pathways were primarily associated with the tumor necrosis factor (TNF) signaling pathway and dopaminergic synapse. The application of RMNS effectively promoted early awakening in comatose patients with severe TBI. Moreover, differentially expressed miRNAs might reduce neuronal apoptosis and increase dopamine levels by regulating target gene expression, thus participating in the specific biological process after arousal therapy. Our study provided novel targets for further research on the molecular mechanisms of RMNS arousal treatment and a new way to treat neurotraumatic diseases.

R\'esum\'eLet$$E/{\mathbb {Q}}$$E/Qbe a CM elliptic curve andpa prime of good ordinary reduction forE. We show that if$$\text {Sel}_{p^\infty }(E/{\mathbb {Q}})$$Selp∞(E/Q)has$${\mathbb {Z}}_p$$Zp-corank one, then$$E({\mathbb {Q}})$$E(Q)has a point of infinite order. The non-torsion point arises from a Heegner point, and thus$${{\,\mathrm{ord}\,}}_{s=1}L(E,s)=1$$ords=1L(E,s)=1, yielding ap-converse to a theorem of Gross–Zagier, Kolyvagin, and Rubin in the spirit of [49, 54]. For$$p>3$$p>3, this gives a new proof of the main result of [12], which our approach extends to all primes. The approach generalizes to CM elliptic curves over totally real fields [4].

Ticagrelor provides more rapid, potent, and consistent anti-platelet efficacy than clopidogrel. This randomized trial aimed to evaluate the anti-inflammation effects of ticagrelor versus clopidogrel on thrombus aspirated from the ST-elevation myocardial infarction (STEMI) patients.A total of 98 patients with STEMI and intended percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (600-mg loading dose) or ticagrelor (180-mg loading dose), of whom 55 with large thrombus burden underwent thrombus aspiration during PCI. Thrombus specimens were successfully aspirated from 49 patients. Finally, 24 patients in the clopidogrel group and 23 in the ticagrelor group completed the study. Inflammatory cells within thrombi were assessed by hematoxylin-eosin and immunohistochemistry stainings.Compared with the clopidogrel group, the number of total inflammatory cells per mmIn patients with undergoing PCI for STEMI, the loading dose ticagrelor regimen was associated with a reduction in inflammatory cell infiltration within thrombus compared with the loading dose clopidogrel regimen.

Tuning metal–support interactions (MSIs) is an important strategy in heterogeneous catalysis to realize the desirable metal dispersion and redox ability of metal catalysts. Herein, we use pre-reduced Co3O4 nanowires (Co-NWs) in situ grown on monolithic Ni foam substrates to support Ag catalysts (Ag/Co-NW-R) for soot combustion. The macroporous structure of Ni foam with crossed Co3O4 nanowires remarkably increases the soot–catalyst contact efficiency. Our characterization results demonstrate that Ag species exist as Ag0 because of the equation Ag+ + Co2+ = Ag0 + Co3+, and the pre-reduction treatment enhances interactions between Ag and Co3O4. The number of active oxygen species on the Ag-loaded catalysts is approximately twice that on the supports, demonstrating the significant role of Ag sites in generating active oxygen species. Additionally, the strengthened MSI on Ag/Co-NW-R further improves this number by increasing metal dispersion and the intrinsic activity determined by the turnover frequency of these oxygen species for soot oxidation compared with the catalyst without pre-reduction of Co-NW (Ag/Co-NW). In addition to high activity, Ag/Co-NW-R exhibits high catalytic stability and water resistance. The strategy used in this work might be applicable in related catalytic systems.

Doxorubicin is a common chemotherapeutic agent in clinic, but myocardial toxicity limits its use. Fibroblast growth factor (FGF) 10, a multifunctional paracrine growth factor, plays diverse roles in embryonic and postnatal heart development as well as in cardiac regeneration and repair. In this study we investigated the role of FGF10 as a potential modulator of doxorubicin-induced cardiac cytotoxicity and the underlying molecular mechanisms. Fgf10+/− mice and an inducible dominant negative FGFR2b transgenic mouse model (Rosa26rtTA; tet(O)sFgfr2b) were used to determine the effect of Fgf10 hypomorph or blocking of endogenous FGFR2b ligands activity on doxorubicin-induced myocardial injury. Acute myocardial injury was induced by a single injection of doxorubicin (25 mg/kg, i.p.). Then cardiac function was evaluated using echocardiography, and DNA damage, oxidative stress and apoptosis in cardiac tissue were assessed. We showed that doxorubicin treatment markedly decreased the expression of FGFR2b ligands including FGF10 in cardiac tissue of wild type mice, whereas Fgf10+/− mice exhibited a greater degree of oxidative stress, DNA damage and apoptosis as compared with the Fgf10+/+ control. Pre-treatment with recombinant FGF10 protein significantly attenuated doxorubicin-induced oxidative stress, DNA damage and apoptosis both in doxorubicin-treated mice and in doxorubicin-treated HL-1 cells and NRCMs. We demonstrated that FGF10 protected against doxorubicin-induced myocardial toxicity via activation of FGFR2/Pleckstrin homology-like domain family A member 1 (PHLDA1)/Akt axis. Overall, our results unveil a potent protective effect of FGF10 against doxorubicin-induced myocardial injury and identify FGFR2b/PHLDA1/Akt axis as a potential therapeutic target for patients receiving doxorubicin treatment.

Background De novo urothelial carcinoma (UC) is a leading cause of death after kidney transplant (KT). The efficacy of various treatments, apart from surgery, and the prognosis for patients with urothelial carcinoma after kidney transplantation remain unclear. Methods We retrospectively reviewed the efficacy of chemotherapy with gemcitabine + cisplatin (GC) or gemcitabine + carboplatin (GCa), bladder infusion chemotherapy, and immunosuppression therapy for de novo UC in kidney transplantation recipients at different sites and T stages. We evaluated the prognosis and compared the difference using Kaplan-Meier analysis and the log-rank test. Results Of the 97 kidney transplantation recipients with de novo UC, 51 (52.6%) were diagnosed with upper urinary tract carcinoma (UTUC), 17 (17.5%) with bladder carcinoma (BC), and 29 (29.9%) with both UTUC and BC. The five-year survival rates for BC, UTUC, and BC + UTUC with ≤ T1 stage were 100%, 88.2%, and 57.7%, respectively, while the survival rates for UTUC, BC + UTUC with ≥ T2 stage were 90.2% and 48.2%. Cyclosporine A significantly improved progression-free survival (PFS) in UTUC with ≤ T1 stage (p = 0.017). Rapamycin significantly improved PFS in UTUC with ≥ T2 stage (p = 0.026). Bladder infusion chemotherapy and GC/GCa chemotherapy had no significant effect on each T stage and site. Patients with UTUC + BC had the poorest overall survival (OS) compared with those with BC and UTUC. Conclusion The prognosis of UC in different sites varies. GC/GCa chemotherapy and bladder infusion chemotherapy appear to have no effect on prognosis. Rapamycin can delay the progression of advanced UTUC.

Quantum simulation enables study of many-body systems in non-equilibrium by mapping to a controllable quantum system, providing a powerful tool for computational intractable problems. Here, using a programmable quantum processor with a chain of 10 superconducting qubits interacted through tunable couplers, we simulate the one-dimensional generalized Aubry-André-Harper model for three different phases, i.e., extended, localized and critical phases. The properties of phase transitions and many-body dynamics are studied in the presence of quasi-periodic modulations for both off-diagonal hopping coefficients and on-site potentials of the model controlled respectively by adjusting strength of couplings and qubit frequencies. We observe the spin transport for initial single- and multi-excitation states in different phases, and characterize phase transitions by experimentally measuring dynamics of participation entropies. Our experimental results demonstrate that the recently developed tunable coupling architecture of superconducting processor extends greatly the simulation realms for a wide variety of Hamiltonians, and can be used to study various quantum and topological phenomena.

Multifunctional supramolecular ultra-tough bionic e-skin with unique durability for human–machine interaction in complex scenarios still remains challenging. Herein, we develop a skin-inspired ultra-tough e-skin with tunable mechanical properties by a physical cross-linking salting-freezing-thawing method. The gelling agent (β-Glycerophosphate sodium: Gp) induces the aggregation and binding of PVA molecular chains and thereby toughens them (stress up to 5.79 MPa, toughness up to 13.96 MJ m−3). Notably, due to molecular self-assembly, hydrogels can be fully recycled and reprocessed by direct heating (100 °C for a few seconds), and the tensile strength can still be maintained at about 100% after six recoveries. The hydrogel integrates transparency (> 60%), super toughness (up to 13.96 MJ m−3, bearing 1500 times of its own tensile weight), good antibacterial properties (E. coli and S. aureus), UV protection (Filtration: 80%–90%), high electrical conductivity (4.72 S m−1), anti-swelling and recyclability. The hydrogel can not only monitor daily physiological activities, but also be used for complex activities underwater and message encryption/decryption. We also used it to create a complete finger joint rehabilitation system with an interactive interface that dynamically presents the user’s health status. Our multifunctional electronic skin will have a profound impact on the future of new rehabilitation medical, human–machine interaction, VR/AR and the metaverse fields.

To screen potential pivotal targets in sepsis through peripheral blood. Septic patients (n = 23) and healthy volunteers (n = 10) were enrolled according to SEPSIS 3.0. Peripheral blood was collected within 24 h of enrollment, RNA-seq was performed on the peripheral blood. The sequencing data was screened for DEGs (p

Background This study aimed to determine the differences among various volumes of condylar osseous patterns and the corresponding dentoskeletal characteristics based on the risk of temporomandibular disorder. Methods Craniofacial spiral computed tomography data of 60 Class II hyperdivergent female adults were divided into normal, resorptive, flattened, and osteophyte groups based on condylar osseous forms. The condylar volumes of each group were compared, and their correlations with the dentoskeletal characteristics were assessed in three dimensions. Pairwise least significant difference tests were used to examine individual pairwise differences between groups, and one-way analysis of variance was used to measure differences among multiple groups. Pearson correlation and Spearman rank correlation analyses were used to determine the correlation between condylar volume and dentofacial characteristics. Statistical significance was established at p Results The condylar volume in the normal group was significantly greater than that in the changed groups, with no significant differences between the subgroups. The decrease in condylar volume was associated with a retruded and clockwise-rotated mandible with shorter rami. Condylar volume was negatively correlated with overjet, the alveolar height of the lower anterior and posterior teeth, sagittal inclinations of the lower teeth, intermolar width of the mandibular first molars, and width between the corresponding alveolar crests. Conclusion Multiple three-dimensional dentoskeletal characteristics of Class II hyperdivergent female adults are correlated with condylar bony changes, regardless of the form. These results could be helpful in indicating potential pathological changes in the temporomandibular joint and in making proper treatment plans for these patients.

FK506 binding proteins (FKBPs) are a highly-conserved group of proteins known to bind to FK506, an immunosuppressive drug. They play different physiological roles, including transcription regulation, protein folding, signal transduction and immunosuppression. A number of FKBP genes have been identified in eukaryotes; however, very little information about these genes has been reported in Locusta migratoria. Here, we identified and characterized 10 FKBP genes from L. migratoria. Phylogenetic analysis and comparison of domain architectures indicated that the LmFKBP family can be divided into two subfamilies and five subclasses. Developmental and tissue expression pattern analysis revealed that all LmFKBPs transcripts, including LmFKBP46, LmFKBP12, LmFKBP47, LmFKBP79, LmFKBP16, LmFKBP24, LmFKBP44b, LmFKBP53, were periodically expressed during different developmental stages and mainly expressed in the fat body, hemolymph, testis, and ovary. In brief, our work depicts a outline but panoramic picture of LmFKBP family in L. migratoria, and provides a solid foundation to further investigate the molecular functions of LmFKBPs.

Fetal magnetic resonance imaging (MRI) is an important adjunct modality for the evaluation of fetal abnormalities. Recently, low-field MRI systems at 0.55 Tesla have become available which can produce images on par with 1.5 Tesla systems but with lower power deposition, acoustic noise, and artifact. In this article, we describe a technical innovation using low-field MRI to perform diagnostic quality fetal MRI.

Globally, lung cancer remains the most commonly diagnosed cancer and the leading cause of cancer-related mortality. Lung adenocarcinoma (LUAD) is a common subtype of lung cancer and carries a poor prognosis. Treatment outcomes biomarkers in LUAD are critical, and there is currently a paucity of data; therefore, there is a need for novel biomarkers and newer therapeutic targets.Bayesian analysis was used to obtain the whole-genome t value of LUAD. Gene set enrichment analysis (GSEA) was conducted to obtain the normalized enrichment scores (NES) of the whole genome, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed using the Gene Set Analysis Toolkit. Herein, we investigated the PPP1R14D expression level at the protein level in LUAD and the impact of PPP1R14D knockdown on the proliferation and apoptosis of LUAD cells in vitro.A total of 483 LUAD samples and 59 normal control samples were included, and 904 differentially expressed genes (DEGs) and 504 LUAD-related genes reported in the literature were obtained. The DEGs showed that PPP1R14D was the most significantly up-regulated gene. Western blot of 30 cases of LUAD tissue and adjacent normal tissue also found that PPP1R14D was significantly highly expressed in cancer tissues. Lentivirus-mediated shRNA strategy effectively inhibited PPP1R14D expression in human LUAD cells DMS53, while PPP1R14D knockdown induced apoptosis and cell proliferation in DMS53 cells.Abnormally up-regulated PPP1R14D promotes the survival and proliferation of tumor cells in human LUAD and may serve as a therapeutic and diagnostic target for LUAD.

PurposeA disconnect often exists between those with the expertise to manage and analyze complex, multi-source data sets, and the clinical, social services, advocacy, and public health professionals who can pose the most relevant questions and best apply the answers. We describe development and implementation of a cancer informatics infrastructure aimed at broadening the usability of community cancer data to inform cancer control research and practice; and we share lessons learned. MethodsWe built a multi-level database known as The Ohio Cancer Assessment and Surveillance Engine (OH-CASE) to link data from Ohio’s cancer registry with community data from the U.S. Census and other sources. Space- and place-based characteristics were assigned to individuals according to residential address. Stakeholder input informed development of an interface for generating queries based on geographic, demographic, and disease inputs and for outputting results aggregated at the state, county, municipality, or zip code levels. ResultsOH-CASE contains 723,410 patient records for Ohioans diagnosed with cancer from 1/1/2006 – 12/31/2017 across 88 counties containing 1215 municipalities and 1197 zip codes. Stakeholder feedback from cancer center community outreach teams, advocacy organizations, public health, and researchers suggests a broad range of uses of such multi-level data resources accessible via a user interface. ConclusionOH-CASE represents a prototype of a transportable model for curating and synthesizing data to understand cancer burden across communities. Beyond supporting collaborative research, this infrastructure can serve the clinical, social services, public health, and advocacy communities by enabling targeting of outreach, funding, and interventions to narrow cancer disparities.

Intensity-modulated radiotherapy (IMRT) is one of the most applied techniques for cancer radiotherapy treatment. The fluence map optimization is an essential part of IMRT plan designing, which has a significant impact on the radiotherapy treatment effect. In fact, the treatment planing of IMRT is an inverse multi-objective optimization problem. Existing approaches of solving the fluence map optimization problem (FMOP) obtain a satisfied treatment plan via trying different coupling weights, the optimization process needs to be conducted many times and the coupling weight setting is completely based on the experience of a radiation physicist. For fast obtaining diverse high-quality radiotherapy plans, this paper formulates the FMOP into a three-objective optimization problem, and proposes a conjugate gradient-assisted multi-objective evolutionary algorithm (CG-MOEA) to solve it. The proposed algorithm does not need to set the coupling weights and can produce the diverse radiotherapy plans within a single run. Moreover, the convergence speed is further accelerated by an adaptive local search strategy based on the conjugate-gradient method. Compared with five state-of-the-art multi-objective evolutionary algorithms (MOEAs), the proposed CG-MOEA can obtain the best hypervolume (HV) values and dose–volume histogram (DVH) performance on five clinical cases in cancer radiotherapy. Moreover, the proposed algorithm not only obtains the more optimal solution than traditional method used to solve the FMOP, but also can find diverse Pareto solution set which can be provided to radiation physicist to select the best treatment plan. The proposed algorithm outperforms dose-volume histogram state-of-the-art multi-objective evolutionary algorithms and traditional method for FMOP on five clinical cases in cancer radiotherapy.

Background Hand foot and mouth disease (HFMD) is a public health concern. Studies on air pollution and the lengths of hospital stay (LOS) of HFMD are scarce. Methods We characterized the clinic demographic features of 5135 hospitalized HFMD in Nanjing, China from 2012 to 2017, and analyzed the association between short-term exposure to PM2.5 as well as its components (OM, BC, SO42−, NH4+, NIT, SOIL and SS) and the LOS of HFMD. Results Among them 98.62% were aged 0–6 years old, and 3772 (73.46%) were hospitalized for seven days or less. The LOS of HFMD children was different in different ages, illness onset years and illness onset seasons (P2.5 concentrations, LOS of HFMD increased by 0.52(0.33, 0.71), 0.50 (95% CI, 0.31–0.69) and 0.46 (95% CI, 0.28–0.65) day in adjusted models at lag 3 days, lag 7days and lag 14 days, respectively. In addition, per IQR increase of BC, SO42−, NH4+, NIT and SOIL were also significantly associated with the LOS of HFMD. Conclusions Our findings corroborated the hypothesis that short-term PM2.5 exposure was associated with increased the LOS of HFMD, and its components (BC, SO42−, NH4+, NIT and SOIL) of PM2.5 might play a key role in the prolonged LOS of HFMD.

Background Long-term prognosis and risk factors of de novo upper tract urothelial carcinoma after renal transplantation were rarely studied. Thus, the aim of this study was to investigate the clinical features, risk factors, and long-term prognosis of de novo upper tract urothelial carcinoma after renal transplantation, especially the impact of aristolochic acid on tumor, using a large sample. Methods 106 patients were enrolled in retrospective study. The endpoints included overall survival, cancer-specific survival, bladder or contralateral upper tract recurrence-free survival. Patients were grouped according to aristolochic acid exposure. Survival analysis was performed using Kaplan–Meier curve. Log-rank test was used to compare the difference. Multivariable cox regression was conducted to evaluate the prognostic significance. Results Median time from transplantation to development of upper tract urothelial carcinoma was 91.5 months. Cancer-specific survival rate at 1, 5, 10 years was 89.2%, 73.2%, 61.6%. Tumor staging (≥ T2), lymph node status (N +) were independent risk factors for cancer-specific death. Contralateral upper tract recurrence-free survival rate at 1, 3, 5 years was 80.4%, 68.5%, 50.9%. Aristolochic acid exposure was independent risk factor for contralateral upper tract recurrence. The patients exposed to aristolochic acid had more multifocal tumors and higher incidence of contralateral upper tract recurrence. Conclusion Both higher tumor staging and positive lymph node status were associated with a worse cancer-specific survival in patients with post-transplant de novo upper tract urothelial carcinoma, which highlighted the importance of early diagnosis. Aristolochic acid was associated with multifocality of tumors and higher incidence of contralateral upper tract recurrence. Thus, prophylactic contralateral resection was suggested for post-transplant upper tract urothelial carcinoma, especially for patients with aristolochic acid exposure.

Phosphorus (P) is an essential and often limiting element that could play a crucial role in terrestrial ecosystem responses to climate warming. However, it has yet remained unclear how different P cycling processes are affected by warming. Here we investigate the response of soil P pools and P cycling processes in a mountain forest after 14 years of soil warming (+4 °C). Long-term warming decreased soil total P pools, likely due to higher outputs of P from soils by increasing net plant P uptake and downward transportation of colloidal and particulate P. Warming increased the sorption strength to more recalcitrant soil P fractions (absorbed to iron oxyhydroxides and clays), thereby further reducing bioavailable P in soil solution. As a response, soil microbes enhanced the production of acid phosphatase, though this was not sufficient to avoid decreases of soil bioavailable P and microbial biomass P (and biotic phosphate immobilization). This study therefore highlights how long-term soil warming triggers changes in biotic and abiotic soil P pools and processes, which can potentially aggravate the P constraints of the trees and soil microbes and thereby negatively affect the C sequestration potential of these forests.