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Background: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use., Patients and Methods: We conducted an early-phase clinical trial of a cultivated, orally delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic 4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors., Results: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes; however, differences in MET4 species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids., Conclusions: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Wallis dynamic stabilization system is a surgical approach in the non-fusion technique of lumbar spine, consisting of interspinous blockers and dacron artificial ligaments that provide stability to the spine while maintaining a degree of motion in the affected segment. Recent studies have demonstrated the significant benefits of Wallis dynamic stabilization system in treating lumbar degenerative diseases. It not only improves clinical symptoms, but also effectively delays complications such as adjacent segmental degeneration. This paper aims to review the literature related to the Wallis dynamic stabilization system and degenerative diseases of the lumbar spine to describe the long-term prognostic effect of this system in the treatment of such diseases. This review provides a theoretical basis and reference for selecting surgical methods to treat degenerative diseases of the lumbar spine.

Integrated cross-scale milli/microlenses offer irreplaceable functions in modern integrated optics with the advantage of reducing the size of the optical system to millimeters or microns. However, the technologies for fabricating millimeter-scale lenses and microlenses are always incompatible, which makes the successful fabrication of cross-scale milli/microlenses with a controlled morphology challenging. Here, ion beam etching is proposed as a means to fabricate smooth millimeter-scale lenses on various hard materials. In addition, by combining femtosecond laser modification and ion beam etching, an integrated cross-scale concave milli/microlens (27,000 microlenses on a lens with a diameter of 2.5 mm) is demonstrated on fused silica, and can be used as the template for a compound eye. The results provide a new, to the best of our knowledge, route for the flexible fabrication of cross-scale optical components for modern integrated optical systems.

Purpose: Proliferation of T-follicular helper (TFH) CD4+ T cells is a postulated pathogenic mechanism for T-cell non-Hodgkin lymphomas (T-NHL). The inducible T-cell costimulator (ICOS) is highly expressed by TFH, representing a potential target. MEDI-570 is a monoclonal antibody against ICOS, which eliminates ICOS+ cells in preclinical models., Patients and Methods: We report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of MEDI-570 in T-NHL. NCI-9930 is a phase I, first-in-human study of MEDI-570 in relapsed/refractory malignant T-NHL known to express ICOS. MEDI-570 was administered intravenously every 3 weeks for up to 12 cycles. Primary endpoints were safety, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D). Secondary and exploratory endpoints included efficacy parameters and various correlative studies. This study is supported by the National Cancer Institute (NCT02520791)., Results: Twenty-three patients were enrolled and received MEDI-570 at five dose levels (0.01-3 mg/kg). Sixteen (70%) had angioimmunoblastic T-cell lymphoma (AITL); median age was 67 years (29-86) and the median prior lines of therapies was 3 (1-16). Most common grade 3 or 4 adverse events were decreased CD4+ T cells (57%), lymphopenia (22%), anemia (13%), and infusion-related reactions (9%). No DLTs were observed. The RP2D was determined at 3 mg/kg. Analysis of T-cell subsets showed reductions in CD4+ICOS+ T cells reflecting its effects on TFH cells. The response rate in AITL was 44%., Conclusions: MEDI-570 was well tolerated and showed promising clinical activity in refractory AITL. MEDI-570 resulted in sustained reduction of ICOS+ T lymphocytes., (©2023 American Association for Cancer Research.)

One of the important monitoring indicators of the air pollution is atmospheric fine particulate matter (PM 2.5 ), which can induce lung inflammation after inhalation. Coelonin can alleviate PM 2.5 -induced macrophage damage through anti-inflammation. However, its molecular mechanism remains unclear. We hypothesized that macrophage damage may involve the release of inflammatory cytokines, activation of inflammatory pathways, and pyrosis induced by inflammasome. In this study, we evaluated the anti-inflammation activity of coelonin in PM 2.5 -induced macrophage and its mechanism of action. Nitric oxide (NO) and reactive oxygen species (ROS) production were measured by NO Assay kit and dichlorofluorescein-diacetate (DCFH-DA), and apoptosis were measured by Flow cytometry and TUNEL staining. The concentration of inflammatory cytokines production was measured with cytometric bead arrays and ELISA kits. The activation of NF-κB signaling pathway and NLRP3 inflammasome were measured by immunofluorescence, quantitative reverse transcription-polymerase chain reaction and western blot. As expected, coelonin pretreatment reduced NO production significantly as well as alleviated cell damage by decreasing ROS and apoptosis. It decreased generation of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in PM 2.5 -induced RAW264.7 and J774A.1 cells. Moreover, coelonin markedly inhibited upregulating the expression of toll-like receptor (TLR)4 and cyclo-oxygenase (COX)-2, blocked activation of p-nuclear factor-kappa B (NF-κB) signaling pathway, and suppressed expression of NLRP3 inflammasome, ASC, GSDMD, IL-18 and IL-1β. In conclusion, the results showed that coelonin could protect against PM 2.5 -induced macrophage damage via suppressing TLR4/NF-κB/COX-2 signaling pathway and NLRP3 inflammasome activation in vitro., (© 2023 Wiley Periodicals LLC.)

The emergence of quantum magnetism in nanographenes provides ample opportunities to fabricate purely organic devices for spintronics and quantum information. Although heteroatom doping is a viable way to engineer the electronic properties of nanographenes, the synthesis of doped nanographenes with collective quantum magnetism remains elusive. Here, a set of nitrogen-doped nanographenes (N-NGs) with atomic precision are fabricated on Au(111) through a combination of imidazole [2+2+2]-cyclotrimerization and cyclodehydrogenation reactions. High-resolution scanning probe microscopy measurements reveal the presence of collective quantum magnetism for nanographenes with three radicals, with spectroscopic features which cannot be captured by mean-field density functional theory calculations but can be well reproduced by Heisenberg spin model calculations. In addition, the mechanism of magnetic exchange interaction of N-NGs has been revealed and compared with their counterparts with pure hydrocarbons. Our findings demonstrate the bottom-up synthesis of atomically precise N-NGs which can be utilized to fabricate low-dimensional extended graphene nanostructures for realizing ordered quantum phases.

Salmonella enterica is one of the most widespread bacterial pathogens found worldwide, resulting in approximately 100 million infections and over 200 000 deaths per year. Salmonella isolates, termed 'serovars', can largely be classified as either nontyphoidal or typhoidal Salmonella, which differ in regard to disease manifestation and host tropism. Nontyphoidal Salmonella causes gastroenteritis in many hosts, while typhoidal Salmonella is human-restricted and causes typhoid fever, a systemic disease with a mortality rate of up to 30% without treatment. There has been considerable interest in understanding how different Salmonella serovars cause different diseases, but the molecular details that underlie these infections have not yet been fully characterized, especially in the case of typhoidal Salmonella. In this review, we highlight the current state of research into understanding the pathogenesis of both nontyphoidal and typhoidal Salmonella, with a specific interest in serovar-specific traits that allow human-adapted strains of Salmonella to cause enteric fever. Overall, a more detailed molecular understanding of how different Salmonella isolates infect humans will provide critical insights into how we can eradicate these dangerous enteric pathogens., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Global trade facilitates the introduction of invasive species that can cause irreversible damage to agriculture and the environment, as well as stored food products. The raisin moth ( Cadra figulilella ) is an invasive pest that poses a significant threat to fruits and dried foods. Climate change may exacerbate this threat by expanding moth's distribution to new areas. In this study, we used CLIMEX and MaxEnt niche modeling tools to assess the potential global distribution of the raisin moth under current and future climate change scenarios. Our models projected that the area of suitable distribution for the raisin moth could increase by up to 36.37% by the end of this century under high emission scenario. We also found that excessive precipitation decreased the probability of raisin moth establishment and that the optimum temperature range for the species during the wettest quarter of the year was 0-18 °C. These findings highlight the need for future research to utilize a combined modeling approach to predict the distribution of the raisin moth under current and future climate conditions more accurately. Our results could be used for environmental risk assessments, as well as to inform international trade decisions and negotiations on phytosanitary measures with regards to this invasive species.

Background: This phase 2 trial aimed to compare adjuvant icotinib with observation in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage IB non-small cell lung cancer (NSCLC)., Methods: We performed a randomised, open-label, phase 2 trial from May 1, 2015 to December 29, 2020 at Sun Yat-sen University Cancer Center in China. Patients with completely resected, EGFR-mutant, stage IB (the 7th edition of TNM staging) NSCLC without adjuvant chemotherapy were randomised (1:1) to receive adjuvant therapy with icotinib (125 mg, three times daily) for 12 months or to undergo observation until disease progression or intolerable toxicity occurred. The primary endpoint was 3-year disease-free survival (DFS). CORIN (GASTO1003) was registered with Clinicaltrials.gov, with the number NCT02264210., Findings: A total of 128 patients were randomised, with 63 patients in the icotinib group and 65 patients in the observation group. The median duration of follow-up was 39.9 months. The three-year DFS was significantly higher in the icotinib group (96.1%, 95% confidence interval [CI], 91.3-99.9) than in the observation group (84.0%, 95% CI, 75.1-92.9; P = 0.041). The DFS was significantly longer in the icotinib group than in the observation group, with a hazard ratio (HR) of 0.23 (95% CI, 0.07-0.81; P = 0.013). The OS data were immature, with three deaths in the observation arm. In the icotinib group, adverse events (AEs) of any grade were reported in 49 patients (77.8%), and grade 3 or greater AEs occurred in four patients (6.3%). No treatment-related deaths occurred., Interpretation: Our findings suggested that adjuvant icotinib improved the 3-year DFS in patients with completely resected EGFR-mutated stage IB NSCLC with a manageable safety profile., Funding: This study was sponsored by Betta Pharmaceutical Co., Ltd., Competing Interests: LMD and ZLS are employees of Betta Pharmaceuticals Co., Ltd. TW and YP are employees of Hangzhou Repugene Technology Co., Ltd. Other co-authors declare no competing interests., (© 2023 The Author(s).)

The chinaberry yellow-banded longhorn beetle, Anoplophora horsfieldi Hope 1842 (Coleoptera: Cerambycidae) is an important pest on many economic tree species. In this study, the complete mitochondrial genome of A. horsfieldi was determined, which was 15,837 bp in length and contained 37 genes, including 13 protein-coding genes (PCGs), two rRNA, 22 tRNA genes, and a non-coding A + T-rich region. The phylogenetic analysis based on mitochondrial genomes showed that A. horsfieldi is sister to a clade formed by A. chinensis and A. glabripennis ., Competing Interests: The authors report no conflicts of interest and are solely responsible for this paper. There are no relevant financial or non-financial competing interests to report., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Pandemic and endemic strains of Vibrio cholerae arise from toxigenic conversion by the CTXφ bacteriophage, a process by which CTXφ infects nontoxigenic strains of V. cholerae. CTXφ encodes the cholera toxin, an enterotoxin responsible for the watery diarrhea associated with cholera infections. Despite the critical role of CTXφ during infections, signals that affect CTXφ-driven toxigenic conversion or expression of the CTXφ-encoded cholera toxin remain poorly characterized, particularly in the context of the gut mucosa. Here, we identify mucin polymers as potent regulators of CTXφ-driven pathogenicity in V. cholerae. Our results indicate that mucin-associated O-glycans block toxigenic conversion by CTXφ and suppress the expression of CTXφ-related virulence factors, including the toxin co-regulated pilus and cholera toxin, by interfering with the TcpP/ToxR/ToxT virulence pathway. By synthesizing individual mucin glycan structures de novo, we identify the Core 2 motif as the critical structure governing this virulence attenuation. Overall, our results highlight a novel mechanism by which mucins and their associated O-glycan structures affect CTXφ-mediated evolution and pathogenicity of V. cholerae, underscoring the potential regulatory power housed within mucus., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Four polysaccharide fractions were isolated and purified from the culture supernatant and mycelium of Poria cocos, and differences in their immunomodulatory activity were investigated. The average molecular weights of EPS-0M, EPS-0.1M, IPS-0M, and IPS-0.1M were 1.77 × 10 3 , 2.01 × 10 3 , 0.03 × 10 3 and 4.97 × 10 3  kDa, respectively. They all mainly consisted of 5 monosaccharides, including glucose, mannose, galactose, fucose and rhamnose, but with different molar ratios. At a dose of 50 μg/mL, EPS-0M, EPS-0.1M, and IPS-0.1M significantly increased the production of nitric oxide (NO), as well as the mRNA and protein levels of pro-inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in RAW264.7 cells, suggesting that they enhanced macrophage-mediated innate immunity. Moreover, based on the in vitro inflammation model of lipopolysaccharide (LPS)-stimulated RAW264.7 cells, EPS-0M, EPS-0.1M and IPS-0M but not IPS-0.1M could inhibit the LPS-induced excessive inflammatory response, including NO, IL-6, TNF-α, IL-1β production and gene transcription. Interestingly, IPS-0M showed a relatively poor immunostimulatory effect, but had the strongest inhibitory effect against the LPS-induced RAW264.7 inflammatory response. Furthermore, our results indicate that the nuclear factor-kappa B (NF-κB) pathway is associated with the immunomodulatory effects of the polysaccharide samples on RAW264.7 cells. This study can provide a reference for the more targeted application of different polysaccharide components from Poria cocos for human health., Competing Interests: Conflict of interest There are no conflicts to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

To improve the versatility of the sodium alginate-loaded bio-hydrogels, Antheraea pernyi silk gland protein/sodium alginate drug-loaded hydrogels were prepared by using an eco-friendly multiple network cross-link technology. Fourier transform infrared (FT-IR) spectroscopy and UV-Vis spectrophotometer were used separately to evaluate the chemical structure and drug release behavior of drug-loaded hydrogels. The antibacterial drug carrier gels were evaluated by using inhibition zone test against the S. aureus and E. coli . The CCK-8 assay was used to assess the biocompatibility of drug loaded hydrogels. The FT-IR results showed that there was a strong interaction within the drug loaded hydrogels, and the ASGP was beneficial to enhance the interaction within the drug loaded hydrogels. UV-Vis spectrophotometer results indicated the cumulative release reached 80% within 400 min. Antibacterial bio-hydrogels had a good antibacterial property, especially the antibacterial bio-hydrogels with bacitracin exhibits superior to other antibacterial agents. The drug-loaded bio-hydrogels exhibited the adhesion and proliferation of RSC96 cells and perfected biocompatibility. This provides a new idea for further research and development of tissue-friendly drug-loaded biomaterials.

The adult female, larva, and pupa of Glossosoma (Lipoglossa) kamael Malicky 2012 from Qinghai Province, China, are described and illustrated. Molecular associations are based on COI sequences. The immature stages of the subgenus Lipoglossa are described for the first time. Biological and habitat information of G. kamael are presented.

Objective: To compare the efficacy of high-flow nasal cannula oxygen therapy (HFNC) and non-rebreather face mask (NRFM) in the treatment of mild acute carbon monoxide poisoning (ACOP) in reducing carboxyhemoglobin (COHb) , and to explore the feasibility of HFNC in the treatment of ACOP. Methods: Patients with mild ACOP with COHb >10% who were admitted to the emergency department of Northern Jiangsu People's Hospital from January 2015 to December 2020 were analyzed, and those with altered consciousness, mechanical ventilation and those requiring hyperbaric oxygen therapy were excluded. The patients were divided into HFNC group and NRFM group according to the oxygen therapy used in the emergency department. The COHb decline value and COHb half-life in the two groups were observed. Results: Seventy-one patients were enrolled, including 39 in the NRFM group and 32 in the HFNC group. The baseline COHb in the HFNC group was 24.8%±8.3%, and that in the NRFM group was 22.5%±7.1%, with no significant difference between the two groups ( t =1.27, P =0.094) . At 60 min, 90 min and 120 min of treatment, COHb in both groups decreased, but the COHb in HFNC group was lower than that in NRFM group at the same time point ( P <0.05) . After 1 h of treatment, the COHb decrease in the HFNC group (16.9%±4.5%) was significantly higher than that in the NRFM group (10.1%±7.8%) ( t =4.32, P =0.013) . The mean half-life of COHb in the HFNC group (39.3 min) was significantly lower than that in the NRFM group (61.4 min) ( t =4.69, P =0.034) . Conclusion: HFNC treatment of mild ACOP can rapidly reduce blood COHb level, it is a potential oxygen therapy method for clinical treatment of ACOP.

In Sichuan province, walnuts, consisting of Juglans regia , Juglans sigillata , and the hybrid J. regia × J. sigillata , are commercially important edible nuts, and J. regia is the most widespread plant. To date, the diversity and distribution of fungi inhabiting on Juglans have not received enough attention, although there have been studies focusing on pathogens from fruit and stem. In order to update the checklist of fungi associated with Sichuan walnuts, a survey on fungi associated with the three Juglans species from 15 representative regions in Sichuan was conducted. In this article, ten fungi distributed in two classes of Ascomycota (Dothideomycetes and Sordariomycetes) were described based on morpho-molecular analyses, and two novel species, Neofusicoccum sichuanense and Sphaerulina juglandina , a known species of Ophiognomonia leptostyla , and seven new hosts or geographical records of Cladosporium tenuissimum , Diatrypella vulgaris , Helminthosporium juglandinum , Helminthosporium velutinum , Loculosulcatispora hongheensis , Periconia byssoides , and Rhytidhysteron subrufulum were included. Morphological descriptions and illustrations of these fungi are provided., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Wang, Liu, Yang, Zeng, Wang, Liu and Yang.)

Five new species of genus Tinodes Curtis 1834 from China are described, illustrated, and diagnosed based on distinctive characters of male genitalia, including Tinodes falcata n. sp., T. xuzhouorum n. sp., T. shunhuangshanensis n. sp., T. yangae n. sp., and T. lini n. sp. Tinodes falcata n. sp. differs from other members of Tinodes in having an unpaired falcate and strongly sclerotized phallic sheath process. Tinodes xuzhouorum n. sp. differs from T. charmi Malicky 2009 by the relative lengths of the superior appendages and the phallus, the position of the ejaculatory duct, and the angle formed by tergum IX and the superior appendages in lateral view. Tinodes shunhuangshanensis n. sp. can be distinguished from T. sartael Malicky 2017 by the phallic sheath process splitting into paired dorsal branches and an apically incised ventral branch. Tinodes yangae n. sp. differs from T. eris Malicky & Sangpradub 2001 by the dorsal phallic sheath process having extra paired vertical branches. Tinodes lini n. sp. differs from T. dactringa Johanson & Oláh 2008 by the phallic guide with a pair of closely attached dorsal branches.

The use of dynamic navigation technology in edentulous jaw implant restoration can solve many problems associated with traditional edentulous jaw implant restoration. The benefits of dynamic navigation include fine positioning guidance, restoration-guided surgery, good aesthetic results, and the possibility of simultaneous conceptual design and real-time implant guidance, as well as the transition from "blind" to "direct" vision during the implantation. It can guide clinicians and adjust the plan in real time, improve the efficiency of communication between the clinician, technician, and patient throughout the process and so on. The workflow, current clinical application and challenges, accuracy analysis, and limitations of the dynamic navigation technology in the edentulous jaw are discussed in this paper, as well as an outlook on its future development, with the goal of contributing to the clinical development of dynamic navigation-guided implantology in the edentulous jaw.

Engagement of the sarcoplasmic reticulum (SR) Ca 2+ stores for excitation-contraction (EC)-coupling is a fundamental feature of cardiac muscle cells. Extracellular matrix (ECM) proteins that form the extracellular scaffolding supporting cardiac contractile activity are thought to play an integral role in the modulation of EC-coupling. At baseline, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show poor utilisation of SR Ca 2+ stores, leading to inefficient EC-coupling, like developing or human CMs in cardiac diseases such as heart failure. We hypothesised that integrin ligand-receptor interactions between ECM proteins and CMs recruit the SR to Ca 2+ cycling during EC-coupling. hiPSC-CM monolayers were cultured on fibronectin-coated glass before 24 h treatment with fibril-forming peptides containing the integrin-binding tripeptide sequence arginine-glycine-aspartic acid (2 mM). Micropipette application of 40 mM caffeine in standard or Na + /Ca 2+ -free Tyrode's solutions was used to assess the Ca 2+ removal mechanisms. Microelectrode recordings were conducted to analyse action potentials in current-clamp. Confocal images of labelled hiPSC-CMs were analysed to investigate hiPSC-CM morphology and ultrastructural arrangements in Ca 2+ release units. This study demonstrates that peptides containing the integrin-binding sequence arginine-glycine-aspartic acid (1) abbreviate hiPSC-CM Ca 2+ transient and action potential duration, (2) increase co-localisation between L-type Ca 2+ channels and ryanodine receptors involved in EC-coupling, and (3) increase the rate of SR-mediated Ca 2+ cycling. We conclude that integrin-binding peptides induce recruitment of the SR for Ca 2+ cycling in EC-coupling through functional and structural improvements and demonstrate the importance of the ECM in modulating cardiomyocyte function in physiology.

One-way water transport is a predominant feature of comfortable textiles used in daily life. However, shortcomings related to the textiles include their poor breathability and durability. In this study, low-cost and eco-friendly PLA/low-melt (polylactic acid) LMPLA-thermoplastic polyurethane (TPU) membranes were fabricated through a needle punch/hot press and electrospinning method. The micro-/nano-channels, used for the first time, endowed the composite membranes with robust, breathable, moisture-permeable, and abrasion-resistant performance. By varying the nano- layer thickness, the resulting 16-40 μm membranes exhibited excellent one-way water transport, robust breathability and moisture permeability, and good abrasion resistance. Nano-layer thickness was found to be a critical performance factor, balancing comfort and protection. These results may be useful for developing low-cost, eco-friendly, and versatile protective products for medical application.

In this study, we report static and perfused models of human myocardial-microvascular interaction. In static culture, we observe distinct regulation of electrophysiology of human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) in co-culture with human cardiac microvascular endothelial cells (hCMVECs) and human left ventricular fibroblasts (hLVFBs), including modification of beating rate, action potential, calcium handling, and pro-arrhythmic substrate. Within a heart-on-a-chip model, we subject this three-dimensional (3D) co-culture to microfluidic perfusion and vasculogenic growth factors to induce spontaneous assembly of perfusable myocardial microvasculature. Live imaging of red blood cells within myocardial microvasculature reveals pulsatile flow generated by beating hiPSC-CMs. This study therefore demonstrates a functionally vascularized in vitro model of human myocardium with widespread potential applications in basic and translational research., Competing Interests: The authors declare no competing interests., (© 2022 Imperial College London.)

This is a cytometry by time-of-flight (CyTOF) staining protocol for hematopoietic-derived cells, that leverages live-cell barcoding using receptor-type tyrosine-protein phosphatase C (CD45) antibodies conjugated to metal isotopes in combination with DNA-based palladium barcoding to multiplex up to 40 samples. In this protocol, DNA-based barcoding is performed before surface and intracellular immunostaining, which reduces the batch effects that result from day-to-day variations in staining and instrument sensitivity. This protocol also reduces antibody consumption and eliminates the need for repeated instrument adjustment., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Here, 20 Cu-20 Ni-54 NiFe 2 O 4 -6 NiO (wt%) cermets were prepared via the powder metallurgy process, and the electrolytic corrosion behavior of the cermets at 880 °C and 960 °C was studied through the microstructure analysis by SEM and EDS. Results show that the ceramic phase is seriously affected by chemical corrosion at 880 °C electrolysis, and it is difficult to form a dense ceramic surface layer. A dense ceramic surface layer is formed on the bottom of the anode electrolyzed at 960 °C, and the dense layer thickens with the extension of the electrolysis time. The formation of the dense surface layer is mainly caused by the oxidation of Ni. The oxidation rate of the metallic phase and the corrosion rate of the ceramic phase have an important effect on the formation of the dense layer. In the corrosion process of NiFe 2 O 4 phase, preferential corrosion of Fe element occurs first, and then NiO phase is precipitated from NiFe 2 O 4 phase. After the NiO is dissolved and corroded, the NiFe 2 O 4 grains collapse and the ceramic phase peels off from the anode.

Tetragonal tungsten bronze (TTB) based oxides constitute a large family of dielectric materials which are known to exhibit complex distortions producing incommensurately modulated superstructures as well as significant local deviations from their average symmetry. The local deviations produce diffuse scattering in diffraction experiments. The structure as well as the charge dynamics of these materials are anticipated to be sensitive to defects, such as cation or oxygen vacancies. In this work, in an effort to understand how the structural and charge dynamical properties respond to these two types of vacancy defects, we have performed measurements of dielectric susceptibilities and single crystal diffraction experiments of two types of TTB materials with both 'filled' (Ba 2 NdFeNb 4 O 15 and Ba 2 PrFeNb 4 O 15 ) and 'unfilled' (Sr 0.5 Ba 0.5 Nb 2 O 6 ) cation sublattices. We also perform these measurements before and after oxygen annealing, which alters the oxygen vacancy concentrations. Surprisingly, we find that many of the diffuse scattering features that are present in the unfilled structure are also present in the filled structure, suggesting that the random fields and disorder that are characteristic of the unfilled structure are not responsible for many of the local structural features that are reflected in the diffuse scattering. Oxygen annealing clearly affected both color and dielectric properties, consistent with a diminishment of the oxygen vacancy concentration, but had little effect on observed diffuse patterns., (© 2022 IOP Publishing Ltd.)

Type I interferons (IFN-Is) are central regulators of anti-tumor immunity and responses to immunotherapy, but they also drive the feedback inhibition underlying therapeutic resistance. In the present study, we developed a mass cytometry approach to quantify IFN-I-stimulated protein expression across immune cells and used multi-omics to uncover pre-therapy cellular states encoding responsiveness to inflammation. Analyzing peripheral blood cells from multiple cancer types revealed that differential responsiveness to IFN-Is before anti-programmed cell death protein 1 (PD1) treatment was highly predictive of long-term survival after therapy. Unexpectedly, IFN-I hyporesponsiveness efficiently predicted long-term survival, whereas high responsiveness to IFN-I was strongly associated with treatment failure and diminished survival time. Peripheral IFN-I responsive states were not associated with tumor inflammation, identifying a disconnect between systemic immune potential and 'cold' or 'hot' tumor states. Mechanistically, IFN-I responsiveness was epigenetically imprinted before therapy, poising cells for differential inflammatory responses and dysfunctional T cell effector programs. Thus, we identify physiological cell states with clinical importance that can predict success and long-term survival of PD1-blocking immunotherapy., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The male adult of Molannatruncata Ge, Peng & Sun sp. nov. is described and illustrated based on material collected in Si-chuan, China. It could be diagnosed by the subtriangular superior appendages when viewed dorsally, and by the mesal appendages each having a slender thorn and inferior appendages with a tiny inner process. Based on morphology of genitalia, we provide a dichotomous key to adult males of Molanna from the Oriental region. The DNA barcodes (partial mtCOI sequences) of M.truncata sp. nov. are generated and compared with existing sequences of Molanna species from Oriental and Palearctic regions. The mean intraspecific divergence of Molanna was 1.58% with a maximum of 8.50% in M.moesta . The Automatic Barcode Gap Discovery (ABGD) analysis of Molanna inferred 9 OTUs and thresholds of interspecific divergence of 10%. Divergence of M.truncata sp. nov. haplotypes from all other Molanna haplotypes ranged from 10.1% to 18%. We discuss distribution and potential groups of species within the Oriental Molanna species based on morphology., (Xin-yu Ge, Lang Peng, Jie Du, Chang-hai Sun, Bei-xin Wang.)

Objective: To investigate the epidemiology, characteristics and risk factors of functional constipation (FC) in children aged 0-4 years in Xi'an. Methods: From October, 2020 to June, 2021, a prevalence survey was conducted among 2 615 children aged 0-4 years in Xi'an by group sampling. The related factors of FC were investigated by questionnaire designed based on Rome Ⅳ diagnostic criteria.The children were divided into FC group and non-FC group. The prevalence, symptoms and signs of FC were analyzed, and its risk factors were analyzed by multivariate Logistic regression. Results: A total of 2 985 valid questionnaires were handed out, and 2 711 (90.8%) were received back. A total of 2 615 questionnaires were valid, with an effective rate of 96.5%. There were 1 338 males (51.2%) and 1 277 females (48.8%). There were 260 cases in FC group and 2 355 cases in non-FC group. The prevalence of FC in children aged 0-4 years in Xi 'an was 10.6%.There were significant differences in FC prevalence among children of different ages and sex (χ 2 =14.58,4.39, both P <0.05), but not in urban or rural residence (χ 2 =3.29, P =0.070). The main symptoms of FC group in the last month were large-diameter feces (73.5%, 191/260), painful defecation or dry and hard defecation (65.8%, 171/260). In the last month, FC group had higher incidences of the Bristol type 1, 2 and 3 stool, fecal retention, prolonged defecation, abdominal pain and incomplete defecation compared with non-FC group, with statistical significance (all P <0.05). Parental history of childhood constipation ( OR =2.13, 95% CI 1.55-2.92), fever in the last month ( OR =1.86, 95% CI 1.32-2.63), history of constipation ( OR =3.24, 95% CI 2.46-4.26) and taking probiotics in the last month ( OR =1.45, 95% CI 1.11-1.91) were risk factors of FC in children aged 0-4 years. Stratified with age, the results showed that complementary feeding earlier than 5 months of age or later than 6 months of age ( OR =2.42, 95% CI 1.13-5.20), dry stools during the complementary feeding ( OR =11.27, 95% CI 5.15-24.66), history of constipation ( OR =2.29, 95% CI 1.23-4.29) and taking probiotics in the last month ( OR =1.88, 95% CI 1.10-3.23) were risk factors of FC in children aged 0-<1 year, and breastfeeding ( OR =0.53, 95% CI 0.29-0.94) was a protective factor of FC in children aged 0-<1 year. Family members' recent constipation history ( OR =2.02, 95% CI 1.06-3.85) and past history of constipation ( OR =3.06, 95% CI 1.74-5.38) were FC risk factors for children aged 1-<2 years. Parental history of childhood constipation ( OR =3.12, 95% CI 2.00-4.85), frequency of eating vegetables less than 3 times per week ( OR =3.28, 95% CI 2.00-5.38), history of constipation ( OR =3.66, 95% CI 2.42-5.53) and taking antibiotics in the last month ( OR =1.65, 95% CI 1.06-2.55) were risk factors for FC in children aged 2-4 years. Conclusions: FC in children aged 0-4 years in Xi'an is mainly manifested with large-diameter feces and painful defecation or dry and hard defecation in the last month. It is associated with a variety of risk factors, which are different in different age groups.

The Antheraea Pernyi silk gland protein originates from natural organisms and synthesized by tussah silk glands and has widely potential biomaterial applications due to the superior biocompatibility. This study investigates the Antheraea Pernyi silk gland protein-based drug-loaded bio-hydrogels for bioengineered tissue fabricated by using an eco-friendly method without the harsh extracting process and the usage of toxic chemicals. The drug-loaded bio-hydrogels exhibited a porous structure and interconnected pore walls. The swelling ratio and water absorption of drug-loaded bio-hydrogels were, respectively, above 95% and 1.5 × 10 3 %. The cumulative release of drug loaded hydrogels all reached more than 90% within 4 h, and this indicates the potential of drug-loaded hydrogels as future drug-carrying biomaterials. RSC96 Schwann cells cultured on drug-loaded hydrogels for 72 h under cell culture medium show no toxic effects and more pro-proliferative effects. The results suggest the suitability of drug-loaded bio-hydrogels as natural biopolymer for the potential in vitro RSC96 cell culture platform and other biomaterial applications.

Aims: Takotsubo syndrome (TTS) is an acute heart failure, typically triggered by high adrenaline during physical or emotional stress. It is distinguished from myocardial infarction (MI) by a characteristic pattern of ventricular basal hypercontractility with hypokinesis of apical segments, and in the absence of culprit coronary occlusion. We aimed to understand whether recently discovered circulating biomarkers miR-16 and miR-26a, which differentiate TTS from MI at presentation, were mechanistically involved in the pathophysiology of TTS., Methods and Results: miR-16 and miR-26a were co-overexpressed in rats with AAV and TTS induced with an adrenaline bolus. Untreated isolated rat cardiomyocytes were transfected with pre-/anti-miRs and functionally assessed. Ventricular basal hypercontraction and apical depression were accentuated in miR-transfected animals after induction of TTS. In vitro miR-16 and/or miR-26a overexpression in isolated apical (but not basal), cardiomyocytes produced strong depression of contraction, with loss of adrenaline sensitivity. They also enhanced the initial positive inotropic effect of adrenaline in basal cells. Decreased contractility after TTS-miRs was reproduced in non-failing human apical cardiomyocytes. Bioinformatic profiling of miR targets, followed by expression assays and functional experiments, identified reductions of CACNB1 (L-type calcium channel Cavβ subunit), RGS4 (regulator of G-protein signalling 4), and G-protein subunit Gβ (GNB1) as underlying these effects., Conclusion: miR-16 and miR-26a sensitize the heart to TTS-like changes produced by adrenaline. Since these miRs have been associated with anxiety and depression, they could provide a mechanism whereby priming of the heart by previous stress causes an increased likelihood of TTS in the future., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The coronavirus disease 2019 (COVID-19) pandemic has resulted in over 6 million deaths and significant morbidity across the globe. Alongside common respiratory symptoms, COVID-19 is associated with a variety of cardiovascular complications in the acute and post-acute phases of infection. The suggested pathophysiological mechanisms that underlie these complications include direct viral infection of the myocardium via the angiotensin-converting enzyme 2 (ACE2) protein and a cytokine release syndrome that results in indirect inflammatory damage to the heart. Patients with pre-existing cardiovascular disease and co-morbidities are generally more susceptible to the cardiac manifestations of COVID-19. However, studies have identified a variety of complications in low-risk individuals, including young adults and children. Myocarditis and paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS) are among the adverse events reported in the acute phase of infection. Furthermore, patients have reported cardiac symptoms persisting beyond the acute phase in post-COVID syndrome. This review summarises the acute and chronic cardiac consequences of COVID-19 in low-risk patients, explores the pathophysiology behind them, and discusses new predictive factors for poor outcomes.

Torularhodin, as a new functional carotenoid, possesses great application potential in disease intervention. However, its absorption process and corresponding mechanism have not been studied. In this study, a rat postprandial model was established to explore the absorption and mechanism of torularhodin by investigating the bioavailability of torularhodin in different tissues, the expression of related enzymes and several transporters in the intestine. The results showed that torularhodin entered the intestine faster from micelles (45.21 ± 2.61% was absorbed in the duodenum), and part of it was metabolized into retinol in the anterior segment of the intestine. The expression of genes indicated that absorption of torularhodin in the intestine might require transporter CD36 and SR-B1. The special structure and target organ might be speculated to be the main reason for the low bioavailability of torularhodin in the serum and liver. The results could lay a theoretical foundation for the chemical modification, carrier and subsequent development of torularhodin.

A Gram-stain-positive, orange-pigmented, rod-shaped and flagellated bacterial strain T12 T was isolated from wetland soil in Kunyu Mountain Wetland in Yantai, China. The strain was able to grow at 15-40 °C (optimum 37 °C), at 0.0-9.0% NaCl (optimum 2%, w/v) and at pH 5.5-9.0 (optimum 8.5). A phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain T12 T is a member of the family Planococcaceae, sharing 97.6% and 97.1% sequence similarity with the type strains of Jeotgalibacillus salarius and Jeotgalibacillus marinus, respectively. Genome-based analyses revealed a genome size of 3,506,682 bp and a DNA G + C content of 43.7%. Besides, the genome sequence led to 55.0-74.6% average amino acid identity values and 67.8-74.7% average nucleotide identity values between strain T12 T and the current closest relatives. Digital DNA-DNA hybridization of strain T12 T with the type strains of Jeotgalibacillus proteolyticus and J. marinus demonstrated 19.0% and 20.3% relatedness, respectively. The chemotaxonomic analysis showed that the sole quinone was MK-7. The predominant cellular fatty acids were iso-C 15:0 , anteiso-C 15:0 , C 16:1 ω7c alcohol and iso-C 14:0 . The polar lipids consisted of an unidentified aminolipid, phosphatidylglycerol, diphosphatidylglycerol and two unidentified phospholipids. Based on the polyphasic characterization, strain T12 T is considered to represent a novel species, for which the name Jeotgalibacillus aurantiacus sp. nov. is proposed. The type strain is T12 T (= KCTC 43296  T  = MCCC 1K07171 T )., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Chinese medicine pharmaceutical industry is in the process of digital and intelligent transformation. Intelligent methods are required for efficient analysis and mining of the valuable information in the history data including literature data, pharmaceutical big data, and expert knowledge. Therefore, it is urgent to establish a knowledge-driven intelligent system of pharmaceutical technologies of Chinese medicine for efficient supplying of high-quality Chinese medicinal products. The present study proposed the construction method of the knowledge base of Chinese medicine manufacturing, which was preliminarily established from literature mining, case-based reasoning, and real-time prediction based on vacuum belt drying process optimization. Integrating the technologies(such as deep learning, case-based reasoning, and simulation modeling), pharmaceutical mechanisms, and big data, the knowledge base of Chinese medicine manufacturing can realize knowledge automation and scientific decision-making. It provides an example for upgrading from experience-based manufacturing to intelligent Chinese medicine manufacturing.

Objective: To explore the changes of cerebral blood perfusion in patients with unilateral sudden sensorineural hearing loss (SSNHL) by using the three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) technique. Methods: The clinical characteristics and ASL data of the 32 patients with unilateral SSNHL were retrospectively collected from November 2020 to June 2021 in Beijing Fuxing Hospital of Capital Medical University, among them, there were 7 males and 25 females, aged from 17 to 73 (44.9±14.4) years. According to the location of SSNHL, they were divided into the left SSNHL (L-SSNHL) group (18 cases) and the right SSNHL (R-SSNHL) group (14 cases). A total of 34 healthy volunteers, which including 14 males and 20 females, aged from 24 to 68 (46.2±14.4) years were enrolled from the local community. The parameter of cerebral blood flow (CBF) of each brain area was obtained using the CereFlow software. The Brainnetome Atlas software package based on MATLAB was used for visualization. The independent-samples t test was conducted to compare the difference of cerebral blood perfusion between the unilateral SSNHL group and healthy control (HC) group. Pearson correlation analysis was used to evaluate the correlation between changes in cerebral blood perfusion and clinical scale scores. Results: The CBF of left orbital gyrus part 5, left inferior temporal gyrus part 7, right orbital gyrus part 5, right inferior temporal gyrus part 1, right inferior temporal gyrus part 7, and right parahippocampal gyrus part 3 of the L-SSNHL group were higher than that in the HC group[(49.1±8.8) vs (31.6±10.9)ml·100g -1 ·min -1 ;(42.8±14.3) vs (27.1±13.6)ml·100g -1 ·min -1 ;(51.8±9.4) vs (27.2±11.2)ml·100g -1 ·min -1 ;(38.8±5.7) vs (28.0±9.2)ml·100g -1 ·min -1 ;(38.4±13.8) vs (23.6±10.3)ml·100g -1 ·min -1 ;(42.4±9.4) vs (30.1±12.6)ml·100g -1 ·min -1 ; all P <0.05]. The CBF of left superior frontal gyrus part 7 and left middle frontal gyrus part 3 of the L-SSNHL group were lower than that in the HC group[(48.2±7.9) vs (59.3±13.7)ml·100g -1 ·min -1 ;(46.4±10.3) vs (59.3±16.9)ml·100g -1 ·min -1 ;all P <0.05]. The CBF of left orbital gyrus part 5, right orbital gyrus part 5, right inferior temporal gyrus part 1, and right inferior temporal gyrus part 7 of the R-SSNHL group were higher than that in the HC group[(50.6±7.0) vs (31.6±10.9)ml·100g -1 ·min -1 ;(50.9±8.8) vs (27.2±11.2)ml·100 g -1 ·min -1 ;(38.0±7.2) vs (28.0±9.2)ml·100g -1 ·min -1 ;(35.7±8.5) vs (23.6±10.3)ml·100g -1 ·min -1 ;all P <0.05]; the CBF of right insular part 4 was lower than that in the HC group [(44.2±6.1) vs (54.4±11.3) ml·100 g -1 ·min -1 , P =0.018]. In the L-SSNHL group, the CBF of left superior frontal gyrus part 7 and right orbital gyrus part 5 were negatively correlated with the VAS score( r =-0.83, -0.81, all P <0.05), and the CBF of right orbital gyrus part 5 was negatively correlated with the THI score( r =-0.75, P =0.013). There was no statistically significant correlation between the remaining differences in brain regions and clinical scale scores(all P >0.05). Conclusion: Changes in cerebral blood perfusion in multiple brain regions were found in patients with unilateral SSNHL by using the 3D pCASL technique.

The cancer research community continues to search for additional biomarkers of response and resistance to immune checkpoint treatment (ICT). The ultimate goal is to direct the use of ICT in patients whose tumors are most likely to benefit to achieve a refinement that is equivalent to that of a genotype-matched targeted treatment. Dissecting the mechanisms of ICT resistance can help us characterize ICT nonresponders more efficiently. In this opinion, we argue that there may be additional knowledge gained about immune evasion in cancer by analyzing the loss of the human 9p21.3 locus; as an example, we highlight findings of 9p21.3 loss from the investigator-initiated, pan-cancer INSPIRE study, in which patients were treated with pembrolizumab (anti-PD-1 antibody) ICT., Competing Interests: Declaration of interests P.S., S.Y.C.Y, J.P.B. and H.K.B. have nothing to declare. B.X.W. has received honoraria from AstraZeneca and Tessa Therapeutics. T.J.P. provides consultation for Illumina, Merck, Chrysalis Biomedical Advisors and the Canadian Pension Plan Investment Board (compensated); and receives research support (institutional) from Roche/Genentech. L.L.S. has consulting/advisory arrangements with Merck, Pfizer, AstraZeneca, Roche, Symphogen, Seattle Genetics, GlaxoSmithKline, Voronoi, Arvinas, Tessa, Navire, Relay, Rubius, Janpix, Daiichi Sanyko, Coherus, Marengo, and InteRNA; stock ownership of Agios (spouse); a leadership position in Treadwell Therapeutics (spouse); and their institution receives clinical trials support from Novartis, Bristol-Myers Squibb, Pfizer, Boerhinger-Ingelheim, GlaxoSmithKline, Roche/Genentech, Karyopharm, AstraZeneca, Merck, Celgene, Astellas, Bayer, Abbvie, Amgen, Symphogen, Intensity Therapeutics, Mirati Therapeutics, and Shattucks., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Catheter-based renal denervation has been studied as a potential therapeutic option to reduce high blood pressure (BP). Preclinical studies in some experimental models have demonstrated an antihypertensive effect of renal denervation but reports from clinical trials have been mixed METHODS: We performed a literature search using combinations of the key terms 'Cardiovascular diseases, Clinical trial, Pre-clinical trials, Resistant hypertension, Renal denervation, Ablation technique, Radiofrequency ablation, Ultrasound ablation, RADIANCE SOLO, SYMPLICITY HTN, SYPRAL HTN'. The databases searched were PubMed and OVID Medline., Results: The initial SYMPLICITY HTN-1 AND HTN-2 clinical trials reported significant decreases in office BP but results from the more robustly designed SYMPLICITY HTN-3 trial, which included sham controls and ambulatory BP monitoring, showed no significant antihypertensive effect. Interest in the use of renal denervation in hypertension was once again sparked by favourable results from the SPYRAL HTN-OFF Med trial CONCLUSION: We provide a thorough, critical analysis of key preclinical and clinical studies investigating the efficacy of catheter-based renal denervation as a treatment for hypertension and highlight future areas for research to allow better translation into clinical practice., (© 2022. The Author(s).)

Objectives: To study the clinical efficacy of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain., Methods: A retrospective analysis was performed on the medical data of 30 children with the chief complaint of chronic abdominal pain who were admitted from August 2019 to May 2021. All the children were found to have inflammation of the appendix or intracavitary stool and fecalith by ultrasound and underwent ultrasound-guided endoscopic retrograde appendicitis therapy. The medical data for analysis included clinical manifestations, endoscopic findings, white blood cell count, neutrophil percentage, length of hospital stay, and cure rate., Results: Among the 30 children with chronic abdominal pain, there were 13 boys (43%) and 17 girls (57%), with a mean age of (9±3) years (range 3-15 years) at diagnosis. The median duration of the disease was 12 months, and the median length of hospital stay was 3 days. The children had a median white blood cell count of 6.7×10 9 /L and a neutrophil percentage of 50%±13%. Fecalith and a large amount of feces were flushed out of the appendix cavity for 21 children (70%) during surgery. The follow-up rate was 97% (29/30), and the median follow-up time was 11 months (range 5-26 months). Of the 29 children, abdominal pain completely disappeared in 27 children (93%)., Conclusions: Ultrasound-guided endoscopic retrograde appendicitis therapy is effective in children with chronic abdominal pain caused by feces or fecalith in the appendix cavity.

Cardiac fibroblasts regulate the development of the adult cardiomyocyte phenotype and cardiac remodeling in disease. We investigate the role that cardiac fibroblasts-secreted extracellular vesicles (EVs) have in the modulation of cardiomyocyte Ca 2+ cycling-a fundamental mechanism in cardiomyocyte function universally altered during disease. EVs collected from cultured human cardiac ventricular fibroblasts were purified by centrifugation, ultrafiltration and size-exclusion chromatography. The presence of EVs and EV markers were identified by dot blot analysis and electron microscopy. Fibroblast-conditioned media contains liposomal particles with a characteristic EV phenotype. EV markers CD9, CD63 and CD81 were highly expressed in chromatography fractions that elute earlier (Fractions 1-15), with most soluble contaminating proteins in the later fractions collected (Fractions 16-30). Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with fibroblast-secreted EVs and intracellular Ca 2+ transients were analyzed. Fibroblast-secreted EVs abbreviate the Ca 2+ transient time to peak and time to 50% decay versus serum-free controls. Thus, EVs from human cardiac fibroblasts represent a novel mediator of human fibroblast-cardiomyocyte interaction, increasing the efficiency of hiPSC-CM Ca 2+ handling.

Triple-band terahertz metamaterial absorber with design of miniaturization and compactness is presented in this work. The unit cell of the terahertz absorber is formed by an analogy I-typed resonator (a rectangular patch with two small notches) deposited on top of dielectric sheet and metallic mirror. The miniaturized structure design exhibits three discrete frequency points with near-perfect absorption at terahertz regime. The three absorption peaks could be ascribed to localized resonances of analogy I-typed resonator, while the response positions of these absorption peaks at the analogy I-typed resonator are different by analyzing the near-field patterns of these resonance peaks. Changes in structure parameters of the analogy I-typed resonator are also investigated. Simulation results revealed that the notch sizes of the rectangular patch are the key factor to form the triple-band near-perfect absorption. Further structure optimization is given to demonstrate triple-band polarization insensitive performance. Moreover, actively tunable absorption properties are realized by inserting or introducing vanadium dioxide with adjustable conductivity into the metamaterial structure. It is revealed that the insulator-metal phase transition of vanadium dioxide is the main reason for the modulation of absorption performance. Compared with previous multiple-band absorbers, the device given here has excellent features of high degrees of simplification, miniaturization, and active modulation, these are important in practical applications., (© 2022. The Author(s).)

Hydrogels, as the most typical elastomer materials with three-dimensional (3D) network structures, have attracted wide attention owing to their outstanding features in fields of sensitive stimulus response, low surface friction coefficient, good flexibility, and bio-compatibility. Because of numerous fresh polymer materials (or polymerization monomers), hydrogels with various structure diversities and excellent properties are emerging, and the development of hydrogels is very vigorous over the past decade. This review focuses on state-of-the-art advances, systematically reviews the recent progress on construction of novel hydrogels utilized several kinds of typical polymerization monomers, and explores the main chemical and physical cross-linking methods to develop the diversity of hydrogels. Following the aspects mentioned above, the classification and emerging applications of hydrogels, such as pH response, ionic response, electrical response, thermal response, biomolecular response, and gas response, are extensively summarized. Finally, this review is done with the promises and challenges for the future evolution of hydrogels and their biological applications., (© 2022 Wiley-VCH GmbH.)

Background: Combining immunotherapy and antiangiogenic agents is a promising treatment strategy in endometrial cancer. To date, no biomarkers for response have been identified and data on post-immunotherapy progression are lacking. We explored the combination of a checkpoint inhibitor (nivolumab) and an antiangiogenic agent (cabozantinib) in immunotherapy-naïve endometrial cancer and in patients whose disease progressed on previous immunotherapy with baseline biopsy for immune profiling., Patients and Methods: In this phase II trial (ClinicalTrials.gov NCT03367741, registered December 11, 2017), women with recurrent endometrial cancer were randomized 2:1 to nivolumab with cabozantinib (Arm A) or nivolumab alone (Arm B). The primary endpoint was Response Evaluation Criteria in Solid Tumors-defined progression-free survival (PFS). Patients with carcinosarcoma or prior immune checkpoint inhibitor received combination treatment (Arm C). Baseline biopsy and serial peripheral blood mononuclear cell (PBMC) samples were analyzed and associations between patient outcome and immune data from cytometry by time of flight (CyTOF) and PBMCs were explored., Results: Median PFS was 5.3 (90% CI 3.5 to 9.2) months in Arm A (n=36) and 1.9 (90% CI 1.6 to 3.4) months in Arm B (n=18) (HR=0.59, 90% CI 0.35 to 0.98; log-rank p=0.09, meeting the prespecified statistical significance criteria). The most common treatment-related adverse events in Arm A were diarrhea (50%) and elevated liver enzymes (aspartate aminotransferase 47%, alanine aminotransferase 42%). In-depth baseline CyTOF analysis across treatment arms (n=40) identified 35 immune-cell subsets. Among immunotherapy-pretreated patients in Arm C, non-progressors had significantly higher proportions of activated tissue-resident (CD103+CD69+) ɣδ T cells than progressors (adjusted p=0.009)., Conclusions: Adding cabozantinib to nivolumab significantly improved outcomes in heavily pretreated endometrial cancer. A subgroup of immunotherapy-pretreated patients identified by baseline immune profile and potentially benefiting from combination with antiangiogenics requires further investigation., Competing Interests: Competing interests: SL has received honoraria from AstraZeneca, Merck, Eisai, GSK, and Roche. PAK has participated in Advisory Boards/Scientific Advisory Committees for Alkermes, AstraZeneca, Bayer, GSK, Merck, Pfizer, Tesaro, Vertex, and Repare; and has received institutional funding as Principal Investigator from AstraZeneca, Bayer, Eli Lilly, GSK, Merck, Merck KGaA, Pfizer, and Tesaro/GSK. BXW has no conflicts of interest related to this manuscript; financial disclosures that are not related: he has received honoraria from Tessa Therapeutics and AstraZeneca. MSB has no conflicts of interest related to this manuscript; financial disclosures that are not related: he has received institutional research support from Merck, Transgene, Pharmacyclics, Immune Design, Bristol Myers Squibb, Marker Therapeutics, Sorrento, Viewpoint Molecular Targeting, and Genentech; and is an Advisory Board member (unpaid) for TILT Biotherapeutics, Viewpoint Molecular Targeting, and Sorrento. SLG has received personal fees from AstraZeneca, Immunogen, Sermonix, Elvar Therapeutics, and GSK; and has received grants from AstraZeneca, AbbVie, Pfizer, Rigel, Iovance, Tesaro, Genentech/Roche, PharmaMar, and GSK; and has patents for Sermonix (US patent no. 10,905,659 and 10,258.604). FJB has participated in Advisory Boards for Merck, Eisai, and Agenus; and has received research funding from Eisai, Clovis, ImmunoGen, Merck, and Beigene (all outside the submitted work). TLW has no significant conflicts of interest related to this manuscript; financial disclosures that are not related: she has received research support to the institution for clinical trials from AbbVie, AstraZeneca, Clovis Oncology, Mersana, Mirati, Novartis, Roche Genentech, and Tesaro-GSK. LD has received personal fees from AstraZeneca, Genentech/Roche, MorphoTek, Merck, Inovio, Advance Medical, UpToDate, Cue Biopharma, British Journal of Obstetrics and Gynaecology, Parexel, State of California, Elsevier, ASCO, Expert review, ClearView Heath Care, National Cancer Institute, and JB Learning; and has received grants from Genentech/Roche, Cerulean/NextGen, AbbVie, Tesaro, Pfizer, GSK/Novartis, Morab, MorphoTek, Merck, Aduro BioTech, Syndax, Ludwig, LEAP Therapeutics, Eisai, Lycera, Inovio, and Advaxis; she reports other disclosures from Merck, GSK/Novartis and Genentech/Roche. IC has received travel grants from Tesaro; and is an advisor for AstraZeneca and GSK. PSO has no conflicts of interest related to this manuscript; financial disclosures that are not related to the current work: EMD Serono, Symphogen, Providence, and Tessa Therapeutics. GFF participates in an Advisory Board for GSK; has received honoraria from UpToDate; has received reviewer compensation from Journal of Clinical Oncology and Lancet Oncology; and has received payments to institution for clinical trial conduct from Roche, Syros, GSK, Iovance, Sermonix, Comugen, Cellex, Corcept, and Plexxikon. No disclosures were reported by the other authors., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Circulating tumor DNA (ctDNA) has emerged as a noninvasive biomarker for dynamically monitoring tumors. However, published data on perioperative ctDNA in patients with operable non-small cell lung cancer (NSCLC) are currently limited., Methods: This prospective study recruited 123 patients with resectable stage I to IIIA NSCLC. Preoperative and postoperative plasma samples and tumor tissue samples were subjected to next-generation sequencing with a panel of 425 cancer-related genes. Peripheral blood samples were collected before surgery, postoperatively within 1 month, and every 3 to 6 months for up to 3 years., Results: After 4 exclusions, 119 eligible patients were enrolled from June 2016 to February 2019. Presurgical ctDNA was detectable in 29 of 117 patients (24.8%) and was associated with inferior recurrence-free survival (RFS; hazard ratio [HR], 2.42; 95% CI, 1.11-5.27; P = .022) and inferior overall survival (OS; HR, 5.54; 95% CI, 1.01-30.35; P = .026). Similarly, ctDNA was detected in 12 of 116 first postsurgical samples (10.3%) and was associated with shorter RFS (HR, 3.04; 95% CI, 1.22-7.58; P = .012). During surveillance after surgery, longitudinal ctDNA-positive patients (37 of 119; 31.1%) had significantly shorter RFS (HR, 3.46; 95% CI, 1.59-7.55; P < .001) and significantly shorter OS (HR, 9.99; 95% CI, 1.17-85.78; P = .010) in comparison with longitudinal ctDNA-negative patients. Serial ctDNA detection preceded radiologic disease recurrence by a median lead time of 8.71 months., Conclusions: These results suggest that perioperative ctDNA analyses can predict recurrence and survival, and serial ctDNA analyses can identify disease recurrence/metastasis earlier than routine radiologic imaging in patients with resectable NSCLC., Lay Summary: The utility of serial circulating tumor DNA (ctDNA) monitoring for predicting disease recurrence and survival for early-stage non-small cell lung cancer (NSCLC) has not been well characterized. The detection of ctDNA before and after surgery is associated with the identification of a high risk of disease recurrence and long-term patient outcomes for resectable NSCLC. Perioperative ctDNA analyses identify disease recurrence earlier than routine radiologic imaging. ctDNA analyses can detect minimal residual disease for resectable NSCLC and thus can facilitate early intervention., (© 2021 American Cancer Society.)

The response to visually evoked innate fear is essential for survival and impacts the cognition and behavior of animals to threats in the environment. However, contradictory findings of the interaction of fear and executive behaviors were reported by previous studies. To address this question, the present study investigated the effect of looming stimuli-driven visually innate fear on reward-associated conditioned response and reversal learning in mice with low or high motivation for sucrose. The mice with low motivation exposed to looming stimuli displayed reduced efficiency in the test of conditional response in the fixed ratio 1 schedule and impaired executive motivation as tested in the progressive ratio schedule of reinforcement. However, the high motivated mice exposed to looming stimuli showed an unaffected conditional response but an increased executive motivation. In the reversal learning program, looming stimuli at the middle stage caused deficits in cognitive flexibility in the mice with low and high motivation. Therefore, these results illuminate the impact of visually evoked innate fear on conditional response and reversal learning and further show that the impacts are relevant to internal motivation and external fear stimuli., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Microglial inflammation plays an essential role in neurodegenerative disease. Our previous studies had shown that κ-carrageenan oligosaccharides (KOS) could inhibit the excessive activation of microglia that induced by LPS, while the interrelated mechanisms were still indistinct. Therefore, we detected the inflammatory signaling pathway on LPS-activated microglia that pretreat by different content of KOS to reveal the mechanism on KOS's inhibition of microglia inflammatory response. ELISA was used to detect the effects of KOS on the secretion of interleukin-1 (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and prostaglandin E2 (PG-2) by LPS-activated microglia, respectively. The production of reactive oxygen species (ROS) and nitric oxide (NO) in microglia cells was detected by flow cytometry, and the protein expression of immunoinflammation-related signaling pathways were detected by Western Blot. The results showed that KOS could significantly protected the microglia from the over-activated inflammatory by inhibiting the release of inflammatory cytokines and the oxidative stress response. And KOS could reduce the expression of the protein that related to the TLR4/NF-κB and p38/JNK MAPKs pathways activated by LPS in microglia. However, there may be no specific target of KOS in cells. Therefore, KOS, a natural algal source oligosaccharide, has immunomodulatory effects and can be used as a potential intervention therapy for inflammatory related neurodegenerative diseases., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Micro-opto-electromechanical systems (MOEMSs) are a new class of integrated and miniaturized optical systems that have significant applications in modern optics. However, the integration of micro-optical elements with complex morphologies on existing micro-electromechanical systems is difficult. Herein, we propose a femtosecond-laser-assisted dry etching technology to realize the fabrication of silicon microlenses. The size of the microlens can be controlled by the femtosecond laser pulse energy and the number of pulses. To verify the applicability of this method, multifocal microlens arrays (focal lengths of 7-9 μm) were integrated into a silicon microcantilever using this method. The proposed technology would broaden the application scope of MOEMSs in three-dimensional imaging systems.

Femtosecond laser (fs-laser) is unfavorable in applications for the fabrication of micro-optical devices on hard materials owing to the problems of low fabrication efficiency and high surface roughness. Herein, a hybrid method combining fs-laser scanning, subsequent etching, and annealing was proposed to realize micro-optical devices with low roughness on glass. Compared to traditional laser ablation, the fabrication efficiency in this work was improved by one order of magnitude, and the surface roughness was decreased to 15 nm. Using this method, aspherical convex microlenses and spherical concave microlenses that possess excellent focusing and imaging properties are realized on photosensitive glass. The diameter and height of the microlenses were controlled by adjusting the fabrication parameters. These results indicate that the fs-laser-based hybrid method will open new opportunities for fabricating micro-optical components on hard materials.

A multi-band metamaterial absorber in the terahertz regime using a periodically arranged surface structure placed on an ultra-thin insulating dielectric slab backed by a metallic ground plane is demonstrated in this paper. Its surface structure consists of two identical split rings having opposite opening directions connected by a rectangular patch. The surface structure can have a strong electromagnetic interaction with incident terahertz waves, thereby generating two localized resonance absorption peaks with different frequencies, and the superposition effect of these two absorption peaks gives rise to dual-band absorption. With the aid of the near-field distributions of the two absorption peaks, the physical mechanism of the dual-band absorption is revealed. The dimension changes of the surface structure, including the split rings and the rectangular patch, play a key role in controlling and adjusting the resonance performance of dual-band absorption. Further optimization of the surface structure without increasing the number of sub-resonators provides the ability to increase the number of absorption peaks, which is different from prior multi-band absorption devices that typically require more sub-resonators in their surface structures. Multi-band metamaterial absorbers designed in this paper should have great application prospects in the field of terahertz absorption., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Heart failure affects 1-2% of the adult population and one of the main contributors to its development is cardiomyopathy. Assessing a patient's risk for adverse events in heart failure is challenging and made more difficult by the heterogenous phenotypic expression of the disease. Cardiac MRI has long been a gold standard measure of myocardial function and anatomy due to its high spatial and temporal resolution. More recently, it has been posited to play a more critical role in the diagnosis and prognosis of cardiomyopathy-related heart failure. Given the limitations of more commonly used imaging modalities, increasing the clinical use of cardiac magnetic resonance imaging could potentially improve the prognosis of specific subgroups of patients at risk of adverse cardiac events.

Microglia are the main effector cells of immune response in central nervous system and are important targets for disease prevention and treatment. Κ-carrageenan Oligosaccharide (KOS), obtained by enzymatic hydrolysis from carrageenan of marine red algae, can inhibit the release of inflammatory factors from the over-activated microglia. The mechanism of microglia autophagy induced by KOS and its relationship with inflammation were studied to explore the development prospect of KOS in the research and treatment of inflammatory related diseases. The effect of KOS on inducing autophagy was detected by the secretion of cytokines by lipopolysaccharide (LPS)-activated microglia, respectively. The protein expression of autophagy-related signaling pathways were detected by Western Blot. The results showed that KOS could significantly protect the microglia from over-activated inflammatory by inducing the autophagy and inhibiting the release of inflammatory cytokines. And KOS could reduce the expression of the protein that related to the AMPK/ULK1 pathways in microglia, so as to regulate the autophagy pathway, and inhibit the inflammatory response of over-activated microglia. The study on the effect of KOS on microglia autophagy and excessive inflammatory response will provide a theoretical basis for further studies on the inhibition of nerve injury by regulating microglia autophagy and inflammatory response., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The optimization of extraction of Tetrastigma hemsleyanum Diels et Gilg polysaccharides (THP) using ultrasonic with enzyme method and its monosaccharide compositions and antioxidant activity were investigated in this work. Single-factor experiments and response surface methodology (RSM) were performed to optimize conditions for extraction, and the independent variables were ( X A ) dosage of cellulase, ( X B ) extraction time, ( X C ) ultrasonic power, and ( X D ) ratio of water to the material. The extraction rate of THP was increased effectively under the optimum conditions, and the maximum (4.692 ± 0.059%) was well-matched the predicted value from RSM. THP was consisted of mannose, glucuronic acid, rhamnose, galacturonic acid, glucose, galactose, and arabinose, while glucose was the dominant (26.749 ± 0.634%). According to the total antioxidant capacity assay with the FRAP method, DPPH, and hydroxyl radical scavenging assay, THP showed strong antioxidant activity with a dose-dependent behavior. The results indicated that THP has the potential to be a novel antioxidant and could expand its application in food and medicine.