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Abstract Using a new semi-rigid tetradentate ligand and two cyanometalate building blocks with different steric hindrance, a Fe2Co triangular unit [(Tp)FeIII(CN)3]2CoII(bpmb)·2H2O [1; Tp = hydrotris(pyrazolyl)borate; bpmb = 1,2-bis(3-(2-pyridyl)pyrazol-1-ylmethyl)benzenes] and a Fe2Co2 square unit {[(pzTp)FeIII(CN)3]2[CoII(bpmb)]2}·[(pzTp)FeIII(CN)3]2·4H2O [2; pzTp = tetrakis(pyrazolyl)borate] were synthesized via tunable assembly. Both compounds adopt cis arrangement because of the structural distorted semi-rigid bpmb. Tetranuclear square of 2 was formed due to larger steric hindrance building block of [(pzTp)FeIII(CN)3]− compared with [(Tp)FeIII(CN)3]− in trinculear 1. Magnetic measurements show that antiferromagnetic interactions dominate in 1 and 2. The fitting results of J values suggest a positive correlation between magnetic orbitals overlap of FeIII and CoII ions and Co–N≡C bond angles. Graphical Abstract Two cis arrangement cyanometalate [Fe-Co] clusters were synthesized via tunable assembly with a new semi-rigid tetradentate ligand. The tetranuclear cluster was formed because of larger steric hindrance of pzTp. Both compounds exhibit dominant antiferromagnetic couplings. The fitting results of J values suggest a positive correlation between magnetic orbitals overlap of FeIII and CoII ions and Co–N≡C bond angles.

BACKGROUND AND AIMS: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined. METHODS: Subjects with EoC (n=27) and controls (normal [NL, n=20], Crohn disease [CD, n=14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived. RESULTS: We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r=0.78 and 0.77, P < .001). Among EoC and other EGIDs, there was minimal transcriptomic overlap; and minimal evidence of a strong allergic type 2 immune response compared with other EGIDs. Decreased cell-cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001). CONCLUSION: We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.

Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences.Esophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers sites (n = 311) and 2 independent replication cohorts (n = 83). Inclusion criteria for fibrostenotic EoE were endoscopic rings, stricture, and/or a history of dilation. Endoscopic, histologic, and molecular features were assessed by the EoE Endoscopic Reference Score, EoE Histology Scoring System, EoE Diagnostic Panel, and RNA sequencing. Esophageal endothelial TSPAN12 expression and functional effects on barrier integrity and gene expression were analyzed in vitro.TSPAN12 was the gene most correlated with fibrostenosis (r = -0.40, P.001). TSPAN12 was lower in fibrostenotic EoE and correlated with EoE Endoscopic Reference Score, EoE Diagnostic Panel, and EoE Histology Scoring System (r = 0.34-0.47, P.001). Lower TSPAN12 associated with smaller esophageal diameter (r = 0.44, P = .03), increased lamina propria fibrosis (r = -0.41, P.001), and genes enriched in cell cycle-related pathways. Interleukin (IL)-13 reduced TSPAN12 expression in endothelial cells. Conversely, anti-IL-13 therapy increased TSPAN12 expression. TSPAN12 gene silencing increased endothelial cell permeability and dysregulated genes associated with extracellular matrix pathways. Endothelial cell-fibroblast crosstalk induced extracellular matrix changes relevant to esophageal remodeling.Patients with fibrostenotic EoE express decreased levels of endothelial TSPAN12. We propose that IL-13 decreases TSPAN12, likely contributing to the chronicity of EoE by promoting tissue remodeling through fibroblast-endothelial cell crosstalk.

Data generated at the network edge can be processed locally by leveraging the paradigm of edge computing. To fully utilize the widely distributed data, we concentrate on a wireless edge computing system that conducts model training using decentralized peer-to-peer (P2P) methods. However, there are two major challenges on the way towards efficient P2P model training: limited resources (e.g., network bandwidth and battery life of mobile devices) and time-varying network connectivity due to device mobility or wireless channel dynamics, which receives less attention in recent years. To address these two challenges, this paper studies the impact of topology construction on the P2P training performance. Specifically, we dynamically construct an efficient P2P topology, where model aggregation occurs at the edge. In a nutshell, we first formulate the topology construction for P2P learning (TCPL) problem with resource constraints as an integer programming problem. Then a learning-driven method is proposed to adaptively construct a topology at each training epoch. We evaluate the performance of our proposed algorithm through extensive simulations and physical platform. Evaluation results show that our method can improve the model training efficiency by about 11% with resource constraints, reduce the communication cost by 30% and the network traffic consumption by about 60% under the same accuracy requirement compared to the benchmarks.

A new complex {(NITPBAH)2[Cu(hfac)2]3} 1 derived from carboxy-phenyl-substituted nitronyl nitroxide radical (NITPBAH) and Cu(hfac)2(H2O)2 (NITPBAH = 2-(4-carboxy-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, hfac = hexafuoroacetylacetonato) has been synthesized as well as characterized structurally and magnetically. The single-crystal X-ray diffraction analyses indicated that the complex {(NITPBAH)2[Cu(hfac)2]3} 1 consists of trinuclear five-spin molecule system. Each NITPBAH ligand is bound to two copper atoms with its two oxygen atoms from ONCNO group. Copper atoms display two different coordination types. The central copper atom lies on an inversion center and is six-coordinated in an elongated octahedron using two hfac molecules and two oxygen atoms of ONCNO group from two different NITPBAH ligands. Two terminal copper atoms are five-coordinated in a distorted square-pyramidal environment formed by two hfac molecules and one oxygen atom of ONCNO group from one NITPBAH ligand. The magnetic susceptibility study of the complex {(NITPBAH)2[Cu(hfac)2]3} 1 shows strong antiferromagnetic interactions between Cu(II) ion and NITPBAH radical ligand.

The Sketch is a compact data structure useful for network measurements. However, to cope with the high speeds of the current data plane, it needs to be held in the small on-chip memory (SRAM). Therefore, the product of the counter size and the number of counters must be below a certain limit. With small counters, some will overflow. With large counters, the total number of counters will be small, but each counter will be shared by more flows, leading to poor accuracy. To address this issue, we propose a generic technique: self-adaptive counters (SEAD Counter). When the value of the counter is small, it works as a standard counter. When the value of the counter is large however, we increment it using a predefined probability, so as to represent this large value. Moreover, in the SEAD Counter, the probability decreases when the value increases. We show that this technique can significantly improve the accuracy of counters. This technique can be adapted to different circumstances. We theoretically analyze the improvements achieved by the SEAD Counter. We further show that our SEAD Counter can be extended to three typical sketches and Bloom filters. We conduct extensive experiments on three real datasets and one synthetic dataset. The experimental results show that, compared with the state-of-the-art, sketches using the SEAD Counter improve the accuracy by up to 13.6 times, while the Bloom filters using SEAD Counter can reduce the false positive rate by more than one order of magnitude.

Aiming at the thermal safety issues between the insensitive energetic plasticizer and propellant components, NG/BTTN and insensitive energetic plasticizer BuNENA plasticized propellant was compared by DSC test and cook-off numerical simulation, with the thermal safety property evaluated. The decomposition activation energy Ea and self-ignition temperature Tb of BuNENA plasticized propellant was lower than that of NG/BTTN plasticized propellant. Two kinds of propellant responded in the central area during slow cook-off simulation while in the near shell area during medium cook-off simulation. During fast cook-off simulation, depending on the different thickness of insulator, propellant responded at the area near shell or the area near the caps. The response temperature of two propellants in cook-off simulation agreed with decomposition and self-ignition temperature by DSC, and the decomposition of plasticizer could trigger the response. In cook-off simulation, BuNENA plasticized propellant showed a lower response temperature with a smaller high temperature area before response, resulting a milder response and better thermal safety than NG/BTTN plasticized propellant.

Thiol chemistry is a type of highly efficient chemical reaction between thiols and functional groups. During the past two decades, thiol chemistry has been widely applied in the synthesis and modification of polymers. With the rapid development of polymer chemistry and materials science, more thiol click reactions, which can be efficiently performed under mild conditions, are required. In this research, the synthesis and modification of polymers by thiol-phenylsulfone substitution reactions are reported. A monomer containing two phenylsulfonyl groups is synthesized and the monomer is reacted with bisthiols under mild conditions, leading to the synthesis of novel polymers. Size exclusion chromatography

Oligostilbenes from Iris lactea Pall.var. chinensis (Fisch.) Koidz and their anti-inflammatory activities.

A dual-functional Cd-MOF with high proton conductivity (2.97 × 10−3 S cm−1) and selective recognition of pyridine (LOD = 1.0 × 10−6 M) was obtained. Its composite membrane Cd-MOF@CS-5 has an ultra-high proton conductivity of 3.55 × 10−1 S cm−1.

The luminescent Cu@Cu2S nanozymes prepared by a one-pot method show enhanced catalytic properties in peroxidase- and oxidase-like catalysis and offer an opportunity to visualize the antibacterial process.

Utilizing two different Schiff base ligands, a Dy3 triangular 1 and a Dy3 + Dy3 compound 2 were obtained. The obvious transverse anisotropy and the larger dipole–dipole interactions induce the poor slow magnetic relaxation of 2.

Background Colonic adenocarcinoma (COAD) is a common gastrointestinal tract tumor, and its occurrence and progression are typically associated with genomic instability, tumor-suppressor gene and oncogene mutations, and tumor mutational load. N6-methyladenosine (m6A) modification of RNAs and long non-coding RNA (lncRNA) expression are important in tumorigenesis and progression. However, the regulatory roles of m6A‐associated lncRNAs in the tumor microenvironment, stratification of prognosis, and immunotherapy are unclear. Methods We screened 43 prognostic lncRNAs linked to m6A and performed consistent molecular typing of COAD using consensus clustering. The single-sample Gene Set Enrichment Analysis and ESTIMATE algorithms were used to assess the immune characteristics of different subgroups. Covariation between methylation-related prognostic lncRNAs was eliminated by least absolute shrinkage and selection operator Cox regression. A nomogram was created and evaluated by combining the methylation-related prognostic lncRNA model with other clinical factors. The relationship between the prognostic model grouping and microsatellite instability, immunophenotype score, and tumor mutation burden was validated using R scripts. Finally, we used a linkage map to filter sensitive medicines to suppress the expression of high-risk genes. Three m6A-associated lncRNA modes were identified in 446 COAD specimens with different clinical endpoints and biological statuses. Risk scores were constructed based on the m6A-associated lncRNA signature genes. Patients with lower risk scores showed superior immunotherapy responses and clinical benefits compared to those with higher risk scores. Lower risk scores were also correlated with higher immunophenotype scores, tumor mutation burden, and mutation rates in significantly mutated genes (e.g., FAT4 and MUC16). Piperidolate, quinostatin, and mecamylamin were screened for their abilities to suppress the expression of high-risk genes in the model. Conclusions Quantitative assessment of m6A-associated lncRNAs in single tumors can enhance the understanding of tumor microenvironment profiles. The prognostic model constructed using m6A-associated lncRNAs may facilitate prognosis and immunotherapy stratification of patients with COAD; finally, three drugs with potential therapeutic value were screened based on the model.

The growth and development of taproots are inhibited by cold stress in radish (Raphanus sativus L.). Ethylene-responsive element binding factors (ERF) are key participators in the cold stress response and growth regulation of plants. However, the function of ERF genes in cold tolerance and root development in radish remains elusive. Here, we showed that the secondary growth of radish taproots was inhibited by cold stress. Comparative transcriptome analysis demonstrated that the RsERF40 gene is an important regulator of the cold stress response and root growth regulation. The cold tolerance of transgenic Arabidopsis plants overexpressing the RsERF40 gene was significantly improved. Overexpressing RsERF40 in the cold-sensitive radish genotype and silencing RsERF40 in the cold-tolerant radish genotype indicated that RsERF40 was beneficial for alleviating oxidative damage under cold stress in radish. Transgenic Arabidopsis seedlings showed an increase in the elongation and radial growth of dark-grown roots. RT-qPCR analysis showed that the expression of the cold-related genes (CORs) RsCOR78 and RsCOR413PM1 and the cell wall strengthening-related genes RsCESA6 and RsEXPB3 was upregulated in transgenic Arabidopsis seedlings. Yeast one-hybrid (Y1H) and dual-luciferase reporter assays (DLA) revealed that RsERF40 directly regulates RsCOR78, RsCOR413PM1, RsCESA6 and RsEXPB3 expression, illustrating that RsERF40 enhances cold tolerance and taproot growth by modulating osmotic adjustment and cell wall mechanical strength in radish. In this study, the RsERF40-regulon was firstly found to be a new cold response pathway independent of the CBF-COR pathway conferring cold stress tolerance with increasing radish taproot growth. These results provided novel insight into the molecular mechanism underlying cold stress response and would facilitate the genetic improvement of cold tolerance in radish and other root vegetable crops.

Aiming to solve the problem of low-light-level (LLL) images with dim overall brightness, uneven gray distribution, and low contrast, in this paper, we propose an effective LLL image enhancement method based on the guided filter and multi-scale fusion for contrast enhancement and detail preservation. First, a base image and detail image(s) are obtained by using the guided filter. After this procedure, the base image is processed by a maximum entropy-based Gamma correction to stretch the gray level distribution. Unlike the existing methods, we enhance the detail image(s) based on the guided filter kernel, which reflects the image area information. Finally, a new method is proposed to generate a sequence of artificial images to adjust the brightness of the output, which has a better performance in image detail preservation compared with other single-input algorithms. Experiments show that the proposed method can provide a more significant performance in enhancing contrast, preserving details, and maintaining the natural feeling of the image than the state of the art.

BACKGROUND The cytogenetics of acute myeloid leukemia (AML) increases exponentially with age. Adolescent and young adult (AYA) patients have specific psychosocial and other challenges, influencing their ability to access appropriate treatment. Therefore, in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for AML, inferior outcomes would be observed in AYA patients compared to children. METHODS We defined the age range of AYA patients as 15 to 29 years. Sixty-three patients who underwent allo-HSCT from 1998 to 2020 at Chang Gung Children Hospital were enrolled in this study. Overall survival was the time duration from HSCT to death from any cause. Disease-free survival was the time duration from HSCT to the last follow-up or first event (failure to achieve complete remission, relapse, secondary malignancy, or death from any cause). RESULTS Thirty-seven (59%) patients were

Two new 2-isobutylmalates, named bletimalate C (1) and bletimalate D (2), together with eight known ones (3–10) were isolated from the tubers of Bletilla striata using various chromatographic methods. Their structures were elucidated with the aid of extensive spectroscopic data analyses and by comparison NMR data with those reported in literature. The anti-pulmonary fibrosis activity on TGF-β1-actived NIH/3T3 cells were evaluated for all isolates. Among them, compounds 1, 7 and 10 showed potential anti-pulmonary fibrosis effects with IC50 values of 22.16 ± 1.18 μM, 32.35 ± 3.01 μM and 19.52 ± 4.05 μM, respectively.

In emergency medical facilities location, the hierarchical diagnosis and treatment system plays an obvious role in the rational allocation of medical resources and improving the use efficiency of medical resources. However, few studies have investigated the operational mechanism of hierarchical medical systems in uncertain environments. To address this research gap, this paper proposes a hybrid approach for emergency medical facilities’ location-allocation. In the first stage, in order to concentrate on the utilization of medical resources, we choose alternative facility points from the whole facilities through the entropy weight method (EWM). In the second stage, uncertainty sets are used to describe the uncertain number of patients at emergency medical points more accurately. We propose a robust model to configure large base hospitals based on the robust optimization method. Furthermore, the proposed robust models are applied to the emergency management of Huanggang City under COVID-19. The results show that the optimal emergency medical facility location-allocation scheme meets the actual treatment needs. Simultaneously, the disturbance ratio and uncertainty level have a significant impact on the configuration scheme.

Two cyclic dimer Co(II)-nitronyl nitroxide (NITR) complexes, [Co(hfac)2(NITmPh3Py)]2 (1) and [Co(hfac)2(NIToPh3Py)]2 (2) (NITmPh3Py = 2-[3-methoxyphenyl(3-pyridinyl)]-4,4,5,5-tetramethyl imidazoline−1-oxyl-3-oxide; NIToPy3Ph =2-[2-methoxyphenyl(3-pyridinyl)]-4,4,5,5-tetramethyl imidazoline−1-oxyl-3-oxide; hfac = hexaflfluoroacetylacetonate) have been successfully synthesized and characterized structurally and magnetically. Complex 1 crystallizes in the orthorhombi space group Pbcn with Z = 4, while complex 2 is in monoclinic space group P21/c with Z =2. The magnetic susceptibility studies show strong antiferromagnetic interactions between Co(II) ion and NITR radical in complexes 1 and 2.

Overexpression of various pro-inflammatory factors in microglial cells tends to induce neurodegenerative diseases, for which there is no effective therapy available. Aureonitol (1) and seven analogues, including six previously undescribed [elatumenol A-F (2-4, 6-8, respectively)], along with two new orsellinic acid esters [elatumone A and B (9 and 10)], were isolated from Chaetomium elatum. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including high-resolution mass spectra and one- and two-dimensional NMR, and absolute configurations determined by the Mosher method, dimolybdenum tetraacetate-induced circular dichroism, and theoretical calculations including electronic circular dichroism and NMR. Metabolites 3, 4, 7, and 8 exhibited antineuroinflammatory activity by attenuating the production of inflammatory mediators, such as nitric oxide, interleukin-6, interleukin-1β, tumor necrosis factor-α, and reactive oxygen species. Western blot results indicated 8 decreases the level of inducible nitric oxide synthase and cyclooxygenase-2 and suppresses the expression of Toll-like receptor 4 and nuclear factor kappa-B (NF-κB) as well as the phosphorylation of the inhibitor of NF-κB and p38 mitogen-activated protein kinases in lipopolysaccharide-activated BV-2 microglial cells.

A new type of metal-organic framework, [Cd2(pdc)(H2O)(DMA)2]n (pdc = 3,5-pyrazoledicarboxylic acid; DMA = dimethylamine), named Cd-MOF, was synthesized and characterized. There are regular rectangular pore channels containing a large number of dimethylamine cations in the crystal structure. AC impedance test results show the proton conductivity of Cd-MOF reaches 1.15 × 10-3 S cm-1 at 363 K and 98% RH. In order for its application in fuel cells, the Cd-MOF was introduced into a sulfonated polyphenylene oxide matrix to prepare a hybrid membrane, and the proton conductivity of the hybrid membrane has a high value of 2.64 × 10-1 S cm-1 at 343 K and 98% RH, which is higher than those of most MOF polymer hybrid membranes. The proton conductivity of the hybrid membrane of the SPPO polymer still maintains a certain degree of stability in a wide temperature range. To the best of our knowledge, it is the first proton exchange membrane that combines pyrazolecarboxylate cadmium MOFs and an SPPO polymer with high proton conductivity and good stability. This research may help to further develop the application of MOFs in the field of proton exchange membrane fuel cells.

An efficient electrogenerated chemiluminescence (ECL) nanoprobe (luminol-Au NPs-Ti3C2) was constructed based on Ti3C2Tx MXene (Ti3C2)-mediated in situ formation of Au NPs and anchoring luminol to fabricate a sensitive ECL biosensor for miRNA-155 detection. Herein, Ti3C2 with rich Ti vacancy defects was used as reducing agent, and Au NPs were generated in situ and anchored on the Ti3C2 (Au NPs-Ti3C2). Moreover, the Au NPs-Ti3C2 composites were used as a carrier and provided a large number of sites for the efficient linking of luminol through Au–N bonds to form stable luminol-Au NPs-Ti3C2. The immobilization of ECL emitters is a versatile strategy which not only shortens the electron transmission distance between luminol and electrode, but also provides naked catalytic predominated (111) facets of Au NPs with high electrocatalytic activity, significantly improving the ECL signal of luminol. Furthermore, a catalytic hairpin assembly (CHA) reaction was used, resulting in further amplification of the signal. As a result, the as-prepared ECL biosensor exhibited a linear range from 0.3 fM to 1 nM with a detection limit of 0.15 fM, and demonstrated high reliability of miRNA-155 detection even in human serum samples. The construction of a multifunctional ECL probe with excellent ECL emission opens a new chapter for the application of Ti3C2 in the field of bioanalysis.

The aim of this study was to compare the functional characteristics of mesenchymal stromal cells (MSCs) from a sheep model of traumatic temporomandibular joint (TMJ) fibrous and bony ankylosis. A sheep model of bilateral TMJ trauma-induced fibrous ankylosis on one side and bony ankylosis on the contralateral side was used. MSCs from fibrous ankylosed callus (FA-MSCs) or bony ankylosed callus (BA-MSCs) at weeks 1, 2, 4, and 8 after surgery were isolated and cultured. MSCs derived from the bone marrow of the mandibular condyle (BM-MSCs) were used as controls. The MSCs from the different sources were characterized morphologically, phenotypically, and functionally. Adherence and trilineage differentiation potential were presented in the ovine MSCs. These cell populations highly positively expressed MSC-associated specific markers, namely CD29, CD44, and CD166, but lacked CD31 and CD45 expressions. The BA-MSCs had higher clonogenic and proliferative potentials than the FA-MSCs. The BA-MSCs also showed higher osteogenic and chondrogenic potentials, but lower adipogenic capacity than the FA-MSCs. In addition, the BA-MSCs demonstrated higher chondrogenic, but lower osteogenic capacity than the BM-MSCs. Our study suggests that inhibition of the osteogenic and chondrogenic differentiations of MSCs might be a promising strategy for preventing bony ankylosis in the future.

Bio-inspired jumping robots should achieve stable jumping in field environment. Robots easily lose stability because of the complex terrain and large speed change. Lateral jumping of the robot with four-bar jumping legs under rugged terrain was used as the research object, and a method to achieve good dynamic stability by adjusting the leg attitudes of the robot was proposed. The stability criteria were proposed hierarchically on the basis of the analysis of the jumping mechanism of creatures. Then, the dynamic model of the robot jumping on the slope was established, and the effect of different parameters on dynamic stability was analyzed to carry out the primary selection of parameters. Then, the method of maintaining dynamic stability was proposed. On the basis of ensuring large motion distances and stable driving torques, leg attitudes were considered the optimization parameters. Thus, the robot does not overturn or turn over uncontrollably in the take-off, buffering, and flight phases. Analysis results of robot jumping in plane and 3D space under different terrains prove the feasibility of this method. In particular, the dynamic stability of the robot is better if the take-off direction is considered an optimization parameter. The simulation results also proved the accuracy of the analysis results. The research results provide a theoretical basis to realize stable continuous jumping of bio-inspired biped robots.

The incidence and severity of coronavirus disease 2019(COVID-19) have significant gender differences.Males are more likely to contract severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) than the age-matched females.The virus uses angiotensin-converting enzyme 2(ACE2) receptors to enter human cells.In addition to infecting the respiratory system,ACE2 can also attack the digestive system,nervous system,immune system and so on,due to the various levels of expression in multiple human organs.The testes are one of the ACE2-rich organs.SARS-CoV-2 has been detected in the semen of some COVID-19 patients,which suggests that SARS-CoV-2 may damage the male reproductive system.However,the damage mechanism remains to be studied.The available studies focus on the short-term effect of SARS-CoV-2 on male reproduction and increasing attention has been paid to the long-term effect.This paper briefly describes the possible mechanisms of reproductive cell damage,hypogonadism,and testicular inflammation mediated by SARS-CoV-2 in male COVID-19 patients and points out the existing problems in the current studies,which will broaden the thinking for deciphering the mechanism of reproductive system damage in male COVID-19 patients.

The present study designed and prepared near-infrared responsive sinomenine hydrochloride(SIN) reservoir microneedles and evaluated the feasibility of this type of microneedles in increasing the drug loading and transdermal absorption by characterizing their mechanical properties and in vitro release characteristics.SIN was selected as the model drug, and methoxy poly(ethylene glycol) poly(caprolactone)(mPEG-PCL) copolymers and indocyanine green(ICG) were employed as amphiphilic block copolymers and light inductor to prepare near-infrared responsive nanoparticles.Based on the preparation principle of bubble microneedles, near-infrared responsive SIN reservoir microneedles were designed and prepared.The features of the near-infrared responsive SIN reservoir microneedles were characterized by measuring the morphology, length, mechanical properties, and skin penetration of microneedles.Meanwhile, the drug release performance of reservoir microneedles was evaluated by in vitro release assay.The results showed that the prepared SIN microneedles were conical, with an exposed tip height of about 650 μm.Each needle could load about 0.5 mg of drugs per square centi-meter, and this type of microneedle showed good mechanical properties and performance in skin penetration.The results of the in vitro release assay showed that the 24 h cumulative release per unit area and release rate of the microneedle were 825.61 μg·cm~(-2) and 74.3%, respectively, which indicated that its release kinetics was in line with the first-order kinetic model.This study preliminarily proved that the reservoir microneedle could effectively increase the drug loading with good mechanical properties and release perfor-mance.

The KEYNOTE-590 trial showed that individuals with advanced esophageal cancer who received Pembrolizumab in combination with chemotherapy as a first-line regimen achieved a significant extension of survival. However, this treatment option increases the financial burden on patients and the economic benefits remain to be further evaluated.A Markov model was used to simulate 10-year survival of patients with esophageal cancer from the perspective of United States (US) Medicare payers. We evaluated the economics of Pembrolizumab plus chemotherapy in the PD-L1 positive score (CPS ≥10) and any PD-L1 expression groups, respectively. We estimated total costs, quality-adjusted life years (QALYs), and calculated incremental cost effectiveness ratios (ICERs). Sensitivity analyses were conducted to explore the impact of uncertainties on the results. Subgroup analysis was also performed.The analysis results showed that the ICER for pembrolizumab plus chemotherapy versus chemotherapy alone was $293,513.17/QALYs in the any PD-L1 expression group. This exceeded the threshold of willingness to pay ($150,000/QALYs). ICERs were most sensitive to the cost of pembrolizumab and the ICERs exceeded $150,000/QALYs in all subgroups.Evidence suggests that first-line pembrolizumab in combination with chemotherapy is not a cost-effective option for advanced esophageal cancer in the US, regardless of PD-L1 expression status.

Cyprinids (carps, chubs and minnows) possess well-developed hearing and high sensitivity to sound pressure. The sensitive hearing may assist cyprinids with searching for food, territory defense, and mating behavior. Many paired fishes violently shake in sand and gravel while spawning in rivers. However, no study has examined the ecological importance of the collision sound made by the behavior. This study examined whether cohabitated chubs (Opsariichthys evolans and Zacco platypus) use the collision sound as a signal to locate spawning events so they can be a male satellite or egg eater. Three types of sounds (i.e., collision sound, music noise and ambient noise) were played with or without jerkbaits at the midstream of the Keelung River, Taiwan during the spawning season in 2018 and 2019. Generalized linear mixed models were then built to examine the effects of the sound types and the presence of jerkbaits on the number of individuals that the two chubs attracted. Results showed significantly different levels of attractiveness among the three sound types, with the collision sound attracting most fishes, including both females and males, followed by music noise and ambient noise. The presence of jerkbaits increased the number of fishes attracted, but the effect was only statistically marginally significant. These results suggest that the collision sound as an acoustic signal may be more important than a visual signal for the chubs to locate spawning events of other mating pairs, probably because of the longer transmission distance of the former. The present study demonstrates the ecological meanings of the collision sounds made in association with spawning activities of the chubs and implies that the native chub's spawning activities may be affected by the introduced Z. platypus. More studies on the interactions between these cohabitated chubs will benefit the conservation of native chubs.

In this study, we determine the generalization performance of the long and short questionnaire version (i.e. cross validation: fit model on data set from a new set of ASAs). It involves crowd workers on an online platform. They will be asked to use the questionnaire instrument to rate an interaction between an agent and a human user, which is displayed in a 30 second video clip.