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Purpose: The narrow supralabyrinthine space affects surgical procedures. To study the effect of temporary transposition of geniculate ganglion of facial nerve versus nontransposition on lesion recurrence and facial nerve function in patients with petrous bone cholesteatoma. Methods: A total of 18 patients with petrous bone cholesteatoma involving the facial nerve were treated in our hospital from November 2016 to March 2023. The main surgical method is the extended supralabyrinthine approach assisted by a microscope and an endoscope. We collected and retrospectively analyzed their medical records. Results: Temporary facial nerve transposition was performed in five patients, and nontransposition was performed in 13 patients. Cholesteatoma recurred in three patients with facial nerve nontransposition, whereas none in patients with facial nerve transposition. In this study, except for one case with a second operation, postoperative facial paralysis in other cases was improved to varying degrees, and there was no significant difference between the two groups. Conclusion: Temporary transposition of geniculate ganglion of facial nerve will not affect the postoperative nerve function of patients and can reduce the possibility of cholesteatoma recurrence of the petrous bone. [ABSTRACT FROM AUTHOR]

Peptides and peptide aptamers have emerged as promising molecules for a wide range of biomedical applications due to their unique properties and versatile functionalities. The screening strategies for identifying peptides and peptide aptamers with desired properties are discussed, including high‐throughput screening, display screening technology, and in silico design approaches. The synthesis methods for the efficient production of peptides and peptide aptamers, such as solid‐phase peptide synthesis and biosynthesis technology, are described, along with their advantages and limitations. Moreover, various modification techniques are explored to enhance the stability, specificity, and pharmacokinetic properties of peptides and peptide aptamers. This includes chemical modifications, enzymatic modifications, biomodifications, genetic engineering modifications, and physical modifications. Furthermore, the review highlights the diverse biomedical applications of peptides and peptide aptamers, including targeted drug delivery, diagnostics, and therapeutic. This review provides valuable insights into the advancements in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers. A comprehensive understanding of these aspects will aid researchers in the development of novel peptide‐based therapeutics and diagnostic tools for various biomedical challenges. [ABSTRACT FROM AUTHOR]

Hierarchical classification problems are commonly seen in practice. However, most existing methods do not fully use the hierarchical information among class labels. In this article, a novel label embedding approach is proposed, which keeps the hierarchy of labels exactly, and reduces the complexity of the hypothesis space significantly. Based on the newly proposed label embedding approach, a new angle-based classifier is developed for hierarchical classification. Moreover, to handle massive data, a new (weighted) linear loss is designed, which has a closed form solution and is computationally efficient. Theoretical properties of the new method are established and intensive numerical comparisons with other methods are conducted. Both simulations and applications in document categorization demonstrate the advantages of the proposed method. for this article are available online. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To evaluate the diagnostic performance of short state homeobox 2 (SHOX2) promoter methylation as biomarker for lung cancer identification through aggregating the open published data.We did an electronic search in Pubmed, EMBASE, Ovid, Web of Science, Google Scholar, and the China National Knowledge Infrastructure (CNKI) to identify the publications related to SHOX2 promoter methylation and lung cancer. The diagnostic performance of sensitivity (SEN), specificity (SPE), odds ratio (DOR), and summary receiver operating characteristic (SROC) cure were aggregated by fixed or random effect model. Fagan's nomogram was used to investigate the post‐test diagnostic probability. Deek's funnel plot and line regression test was applied to evaluate the publication bias.In total, 18 clinical studies about SHOX2 promoter methylation and lung cancer were included in the meta‐analysis. The combined diagnostic SEN, SPE, DOR were 0.63 (95% CI = 0.54–0.70), 0.91 (95% CI = 0.87–0.94), and 16.84 (95% CI = 11.18–25.36) in random effect model respectively. The pooled area under the curve (AUC) of SROC was 0.88 (95% CI = 0.84–0.90). The post‐test probability of lung cancer was 88% and 29% when SHOX2 methylated and unmethylated in humoral components given a pre‐test probability of 50%. Deek's funnel plot and regression test indicated no publication bias (p = 0.62).SHOX2 promoter methylation in humoral components may be a potential biomarker for lung cancer diagnosis with relative high diagnostic specificity. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to quantitatively analysis the diagnostic performance of adenomatous polyposis coli (APC) gene promoter methylation in serum or sputum/bronchoalveolar lavage fluid (BLAF) as a biomarker for lung cancer identification through pooling of open published data. Methods: The relevant electronic MEDLINE, EMBASE, Ovid, web of science and CNKI databases were systematically searched to identify the studies related to APC gene promoter methylation for lung cancer diagnosis. Data of true positive (tp), false positive (fp), false negative (fn) and true negative (tn) were extracted from the publications included in the study. The pooled diagnostic sensitivity, specificity and area under summary receiver operating characteristic (SROC) curve (AUC‐SROC) of APC gene promoter methylation were calculated. Publication bias was evaluated by Begg's funnel plot and Egger's line regression test. Results: Fourteen studies associated with APC gene promoter methylation and lung cancer were identified in the databases and finally included in the meta‐analysis. The data was pooled using a random effect model due to significant statistical heterogeneity across the 14 studies (p < 0.05). Using the APC gene promoter methylation as a reference for lung cancer identification, the pooled diagnostic sensitivity and specificity were 0.43 (95% CI: 0.40–0.45), and 0.92 (95% CI: 0.90–0.95), respectively with combined diagnostic positive likelihood ratio (+LR) and negative likelihood ratio (−LR) of 7.15 (95% CI: 3.62–14.12) and 0.63 (95% CI: 0.57–0.71). The pooled diagnostic odds ratio (DOR) and AUC‐SROC of APC gene promoter methylation for lung cancer diagnosis were 9.84 (95% CI: 5.77–16.79) and 0.7, respectively. The Begg's funnel plot and Egger's line regression test both indicated statistical publication bias (t = 5.40, p < 0.05). Conclusions: APC gene promoter methylation in serum or sputum/BLAF is a potential biomarker for lung cancer diagnosis with high specificity. However, due to its low sensitivity, it may not be suitable for lung cancer screening in the general population. [ABSTRACT FROM AUTHOR]

In the present work, a magnetic-assisted DC superimposed nanosecond-pulsed streamer discharge (DC-NPSD) with a 0.4 T parallel magnetic field is developed that achieves good performance for ozone production and toluene degradation. The influence of the assisted parallel magnetic field on the electrical characteristics, streamer propagation behavior, reactive species generation and plasma chemical properties of the DC-NPSD are systematically investigated. The experimental results indicate that better impedance matching of a nanosecond pulsed power supply and a discharge reactor can be realized by superimposing DC voltage (UDC), which facilitates reactive species production and toluene degradation. The discharge current, input energy and reactive species production can be further enhanced by the application of a parallel magnetic field under different pulse and DC voltage conditions. There are two distinct streamer phases in the DC-NPSD: a primary streamer (PS) with longer propagation distance and higher propagation velocity and a secondary streamer (SS) with shorter propagation distance and lower propagation velocity. The propagation velocities of both the PS and the SS increase with increasing UDC. Only PS propagation velocity is accelerated by a parallel magnetic field; however, that of the SS remains almost constant with or without a magnetic field. Both ozone generation and toluene degradation performance are improved by a magnetic field, which is attributed to the lengthened electron motion path under the action of Lorentz force and the constraint effect on energetic electrons in the presence of a parallel magnetic field. [ABSTRACT FROM AUTHOR]

Abstract In the field of label-free biosensing, various transducer materials and strategies are under investigation to overcome the Debye-screening limitation of charged biomolecules. We demonstrate an in-line, impedimetric aptasensor with reduced graphene-oxide (rGO) thin films as transducers to detect prostate specific antigens (PSA) in a physiological buffer solution. Unlike classical electrochemical impedance spectroscopy (EIS), this direct, label-free and fully-electronic biosensor approach does not need any redox markers. As specific capture molecules, short anti-PSA aptamers ensured a close binding of the target molecules to the transducer surfaces. Results showed a limit of detection smaller than 33 pM of PSA and a wide detection range from 0.033 to 330 nM fully covering the clinically relevant range of PSA (0.115–0.290 nM). This promising performance can be attributed to the bipolar electronic transport characteristics of the ultra-thin rGO layers similar to pristine graphene. The attachment of target biomolecules to the films changes the resistance of the rGO thin films. Such an in-line EIS configuration with rGO thin films opens promising prospects for biosensing beyond the Debye-screening limitation, which is a major challenge for conventional semiconductor field-effect devices towards clinical applications. Highlights • We describe a fabrication process for reduced grahene oxide (rGO) biosensors based on interdigitated electrodes (IDEs). • In-line electrochemical impedance spectroscopy was used to read out the rGO-IDEs. • Short aptamers specific to PSA acted as capture molecules. Sensors showed a good response to PSA concentrations. • Detection was possible in a physiological buffer with a Debye-screening length similar to human serum. • The limit of detection and sensor response were fully covering the clinically relevant range for biomedical applications. [ABSTRACT FROM AUTHOR]

Abstract Reduced graphene oxide (rGO) thin films can be exploited as highly sensitive transducer layers and integrated in interdigital micro-electrode systems for biosensing processes. The distinctive bipolar characterisitics of rGO thin films can be modulated by a very low external electric field due to the electrostatic charges of biomolecules. These charges lead to a fast response in the readout signals of rGO based ion sensitive field-effect transistors (ISFETs). The characterisitc changes of rGO ISFETs enable a fast, accurate and reproducible detection of biomolecules. The biosensing mechanism offers a fast and label-free approach for analyte detection in contrast to the classical ELISA method. In this contribution, we introduce a reproducible fabrication process of rGO based field-effect transistors on wafer level. The sensors are functionalized as biosensors to measure N-terminal pro-brain natriuretic peptide (NT-proBNP) in human serum within its clinical range. Our optimized rGO sensor shows very promising electrical properties and can be considered as a proof of concept study for the detection of various analytes. The easy and cost-effective fabrication as well as the versatile usability make this new technological platform an auspicious tool for different sensing applications in future. Highlights • A novel thermal method to reduce graphene-oxide (rGO) on wafer scale for a simultaneous reduction of GO biosensors. • The microstructured rGO under the thin-film Interdigital Electrodes (IDE) can be utilized as field effect transistor (FET) for antigen detection. • The detection of NT-pro BNP was performed in 150 mM human blood serum within the relevant clinical range. • This new fabrication process enables us to create a cost-effective and reproducible label-free biosensor platform. [ABSTRACT FROM AUTHOR]

Scalable and routine integration of chemically exfoliated, graphene-based materials such as graphene oxide (GO) and reduced graphene oxide (rGO) into standard microelectronic fabrication is a tremendous technological challenge, blocking their advancement toward real applications. A unique approach for wafer-scale fabrication of rGO devices by a synergistic combination of chemically exfoliated GO with photolithography processing is realized. Using graphite powder as source material, a GO solution is produced in a newly optimized, low-temperature exfoliation and desalination protocol, resulting in high-quality GO and confirmed by various characterization techniques. As substrates, 4 in. Si/SiO2 or glass wafers were first silanized in a well-controlled, gas-phase procedure. Large-area GO thin films are then realized by standard spin-coating resulting in highly homogeneous, covalently bound layers of controllable thicknesses of 3-7 nm depending on the amount of spin-coatings. The robust thin films undergo routine photolithography for device fabrication, including reduction via thermal annealing into conductive rGO. The top-down fabricated rGO devices display high uniformity with electrical resistances varying within only one order of magnitude over wafer-scale and device yields as high as ≈93% on a wafer. The novel front-end-of-line GO integration protocol offers robust electrical performances for future implementation toward various sensor applications. [ABSTRACT FROM AUTHOR]

Methods The electronic databases of Medline, Cochrane, Embase, Web of Science, OVID and CNKI were systematic searched to identified the case-control or Cohort studies relevant to diagnostic efficacy of serum 1,3-β-D-glucan for invasive fungal infection. The data of true positive (tp), false positive (fp), false negative (fn) and true negative (tn) patients number were extracted from each of the original included studies. The diagnostic sensitivity, specificity and systematic receiver operating characteristic (SROC) curve were calculated and pooled through random or fixed effect method. The publication bias was evaluated by the Deek’s funnel plot. Results Thirty-seven relevant studies were fulfilled the inclusion criteria and included in our present meta-analysis. The combined sensitivity, specificity, positive likely hood ratio (+lr), negative likely hood ratio (-lr) and diagnostic odds ratio(dor) for 1,3-β-D-glucan in diagnosis of invasive fungal infection were 0.83 (95%CI:0.38-0.61), 0.81 (95%CI:0.80-0.82), 5.13 (95%CI:3.98-6.62), 0.23 (95%CI:0.18-0.30), and 29.68 (95%CI:18.94-46.52) respectively. The pooled area under the ROC curve (AUC) was 0.91.The Deek’s funnel plot asymmetry test showed there was no publication bias for 1,3-β-D-glucan in diagnosis of invasive fungal infection of the included 37 studies. Conclusion Serum 1,3-β-D-glucan assay was a promising biomarker for invasive fungal infection diagnosis. [ABSTRACT FROM AUTHOR]

Hair cells (HCs) are the sensory preceptor cells in the inner ear, which play an important role in hearing and balance. The HCs of organ of Corti are susceptible to noise, ototoxic drugs, and infections, thus resulting in permanent hearing loss. Recent approaches of HCs regeneration provide new directions for finding the treatment of sensor neural deafness. To have normal hearing function, the regenerated HCs must be reinnervated by nerve fibers and reform ribbon synapse with the dendrite of spiral ganglion neuron through nerve regeneration. In this review, we discuss the research progress in HC regeneration, the synaptic plasticity, and the reinnervation of new regenerated HCs in mammalian inner ear. [ABSTRACT FROM AUTHOR]

With the rapid development of e-commerce, online consumer review plays an increasingly important role in consumers’ purchase decisions. Most research papers use the quantitative measures of consumer reviews for statistical analysis. Here we focus on analyzing the texts of customer reviews with text mining tools. We propose a new feature selection method called maximizing the difference. Various classification methods such as boosting, random forest and SVM are used to test the performance of the new method along with different evaluation criteria. Both simulation and empirical results show that it improves the effectiveness of the classifier over the existing methods. [ABSTRACT FROM AUTHOR]

Background: Anthocyanins have been proven to be beneficial to the eyes. However, information is scarce about the effects of purple sweet potato (Ipomoea batatas, L.) anthocyanin (PSPA), a class of anthocyanins derived from purple sweet potato roots, on visual health. Objective: The aim of this study was to investigate whether PSPA could have influences on the growth characteristics (cellular morphology, survival, and proliferation) of human retinal pigment epithelial (RPE) cells, which perform essential functions for the visual process. Methods: The RPE cell line D407 was used in the present study. The cytotoxicity of PSPA was assessed by MTT assay. Then, cellular morphology, viability, cell cycle, Ki67 expression, and PI3K/MAPK activation of RPE cells treated with PSPA were determined. Results: PSPA exhibited dose-dependent promotion of RPE cell proliferation at concentrations ranging from 10 to 1,000 mg/ml. RPE cells treated with PSPA demonstrated a predominantly polygonal morphology in a mosaic arrangement, and colony-like cells displayed numerous short apical microvilli and typical ultrastructure. PSPA treatment also resulted in a better platform growing status, statistically higher viability, an increase in the S-phase, and more Ki67+ cells. However, neither pAkt nor pERK were detected in either group. Conclusions: We found that PSPA maintained high cell viability, boosted DNA synthesis, and preserved a high percentage of continuously cycling cells to promote cell survival and division without changing cell morphology. This paper lays the foundation for further research about the damage-protective activities of PSPA on RPE cells or human vision. [ABSTRACT FROM AUTHOR]

The research on unbalanced data classification is a hot topic in recent years. LogitBoost algorithm is an adaptive algorithm that can get much higher prediction precision. But in the face of unbalanced data, this algorithm could produce a large minority class prediction error. In this article, we propose an improved LogitBoost algorithm named BLogitBoost, based on a stratified normalization method which normalizes within class sampling probability first, then normalizes between classes. The experiments on simulation data and empirical data show that the new algorithm can reduce the minority class prediction error significantly. [ABSTRACT FROM AUTHOR]

Identifying customers who are likely to respond to a product offering is an important issue in direct marketing. In this article, we propose a new approach based on repeat buying theory. We argue that the mailing list could be divided into two groups for separate model developments: repeat buyer model and new buyer model. We name this procedure two-group-forecast-and-selection method. Empirical study shows that the new method performs better than the traditional one. [ABSTRACT FROM AUTHOR]

The study of television audience viewing behavior is very important. The results can provide broadcasters and advertisers useful information to increase the effectiveness of television programming and advertising. Based on hazard rate analysis for survival model, this research develops a new statistical model to fit the diffusion pattern of TV programs, which is a measure of the overall popularity of the program and is used as a criterion to sell the television time. The model helps the decision makers at the networks better understand the acceptance of the show and the underlying behavioral patterns of the viewers. It fits the empirical data in Hong Kong very well and outperforms the existing models. This basic model is then extended to the proportional hazard model to study the covariate effects on the likelihood of an individual watching the program at an earlier stage. Advertisers can benefit from these results in targeting their desired customers. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the radioprotective activity of betalains from red beets in mice irradiated by a 60Co gamma (γ) ray (6.0 Gy, at a dose of 1.5 Gy min−1). Mice were randomly divided into five groups, namely the control group and four experimental groups which were given one of four concentrations of betalains from red beets (0, 5, 20 and 80 mg/kg, equivalent to betanin) for 30 days. The four experimental groups of mice were then exposed to the 60Co γ-rays and were given betalains from red beets for a further 3 days. The number of white blood cells, karyota of the femur and the number of micronuclei in polychromatophilic erythrocytes of bone marrow in mice were determined. The activity of superoxide dismutase, catalase, glutathione peroxidase, malondialdehyde, spleen index and thymus index were also determined. The results indicate that the administration of betalains from red beets is radioprotective in mice irradiated by 60Co in vivo. The underlying mechanism remains unclear but appears to be mediated by the antioxidant activity of the betalains from red beets and modulation of the immune system. [Copyright &y& Elsevier]

Abstract: Biodegradable polycaprolactone/chiotosan blends with various proportions were prepared using concentrated acetic acid solutions as solvents. The blends were further processed into thicker membranes using a newly developed processing technique. These membranes were then investigated for their miscibility of components via thermogravimetric examinations, differential scanning calorimetric measurements, and dynamic mechanical analysis as well infrared analysis. The presence of phase separation structures inside the membranes was confirmed although very limited interactions between components were detected. In addition, it was also found that the composition ratio of the membranes did not substantially affect the interactions between the components inside the membranes. [Copyright &y& Elsevier]

Due to global warming, it is necessary to study the influence of extreme climate and concurrent events on crop growth. The study area was the Songliao Plain, where drought events frequently occur. First, the daily meteorological data of 14 meteorological stations from 1981 to 2016 were collected to analyze the temporal and spatial changes in the crop water surplus and deficit index, extreme growing degree-days, and heat stress intensity during different growth stages of maize. Second, the cloud model was used to describe the fuzziness of concurrent events (simultaneous drought and heat), and mutual mapping between qualitative and quantitative data was undertaken. The fuzzy certainty degree of the influence of different degrees of concurrent events on maize was calculated. Third, the copula function was used to describe the randomness of concurrent extreme events and calculate the joint probability distribution and return period. An assessment method was proposed for concurrent events from the perspective of system uncertainty. Finally, we analyzed the relationship between concurrent events and maize yield, which showed different degrees of water deficit and warming trends during each growth period. Crops were most affected by extreme weather during the reproductive growth period (RGP). During the vegetative growth period (VGP), the temperature increase was higher than in other periods, especially in the high-latitude region. The frequency of mild concurrent events was higher during the VGP and RGP. During the vegetative and reproductive period, the average occurrence probability of mild, moderate, and severe concurrent events was 21.9%, 1.7%, and 0.35%, respectively, whereas during the RGP, it was 23.1%, 8.2%, and 0.12%, respectively. The present study provides a meaningful reference for a better understanding of the occurrence laws of drought, heat, and concurrent events during crop growth periods and how to optimize the agricultural management of maize. • Cloud model qualitative and quantitative mapping of drought and heat events. • Copula function was used to describe the randomness of concurrent extreme events. • Vegetative growth periods (VGP) and reproductive growth periods (RGP) were modelled. [ABSTRACT FROM AUTHOR]

mTOR, mLST8 and RAPTOR are the core components of mTORC1, which has been found to be closely related to tumorigenesis. Currently, multiple single nucleotide polymorphisms (SNPs) in mTOR gene (rs2295080, rs17036508 and rs1034528) , mLST8 gene (rs3160 and rs26865) and RPTOR gene (rs1062935, rs3751932, rs3751834, rs12602885) have been extensively studied for their associations with cancer risk. However, the results remained inconclusive and conflicting. Therefore, we here performed a meta-analysis of all available studies to investigate the association between these SNPs and cancer risk. Up to April 2021, 25 related publications were retrieved and included in this meta-analysis. The odds ratios (ORs) and 95% confidence intervals (CIs) calculated by fixed or random effects models were applied to assess the strength of association. Trial Sequential Analysis (TSA) was conducted to weaken the random error and enhance the reliability of evidence. After Bonferroni correction, it was revealed that rs3160, rs26865, rs1062935, rs3751932, rs3751834 and rs10602885 were not associated with cancer risk. However, rs17036508 and rs1034528 showed significant association with total cancer risk. A significant association was also found between rs2295080 and total cancer risk, and stratified analysis by cancer type suggested that rs2295080 was specifically associated with acute lymphoblastic leukemia risk, prostate cancer risk, and breast cancer risk. The present meta-analysis suggested that the rs2295080, rs17036508 and rs1034528 polymorphisms in mTOR gene may be the susceptive factors for cancer development, while the target genetic polymorphisms in mLST8 gene or RPTOR gene may not be associated with cancer risk. However, these findings remain to be confirmed or further reinforced in large and well-designed studies in different ethnic populations. [ABSTRACT FROM AUTHOR]

Abstract: Cytotoxic CD8+ T cells are key effectors in the immunotherapy of malignant and viral diseases. However, the lack of efficient methods for their in vitro priming and expansion has become a bottleneck to the development of vaccines and adoptive transfer strategies. Synthetic artificial antigen-presenting cells (aAPCs) are now emerging as an attractive tool for eliciting and expanding CTL responses. This study reported a novel approach for targeting malignant melanoma with pTRP2-specific cytotoxic T lymphocytes (CTLs) expanded from the C57BL/6 splenocytes by multiple stimulations with aAPCs made by coating H-2Kb-Ig/pTRP2 dimeric complexes, anti-CD28 antibody, 4-1BBL molecules and CD83 molecules to cell-sized latex beads. The induced CTLs exhibited specific lysis against RMA-S cells pulsed with the peptide pTRP2 and H-2Kb+ melanoma cells expressing TRP2, while a murine Lewis lung carcinoma cell line 3LL could not be recognized by the CTLs. The peptide-specific activity was inhibited by anti-H-2Kb monoclonal antibody Y3. Adoptive Transfer of CTLs specific for malignant melanoma expanding by the aAPCs can mediate effective anti-melanoma response. These results suggested the bead-based aAPCs coated with an MHC-Ig/peptide complex, anti-CD28 antibody, 4-1BBL and CD83 could provide a useful tool for the reproducible expansion of specific CTLs for adoptive immunotherapy. [Copyright &y& Elsevier]

AimThe aim of this study was to investigate the novel approach for targeting malignant glioma. MethodsInterleukin-13 receptor α2 (IL-13Rα2)-specific cytotoxic T-cells (CTLs) were induced from the peripheral blood lymphocytes (PBLs) of human leukocyte antigen (HLA)-A2 positive healthy donors by multiple stimulations with artificial antigen-presenting cells (aAPCs) made by coating HLA-A2-IgpIL-13Rα2345–354dimeric complexes, anti-CD28 antibody, and CD83 molecules to cell-sized latex beads. ResultsThe induced CTLs exhibited a specific lysis against T2 cells pulsed with the peptide pIL-13Rα2345–354and HLA-A2glioma cells expressing IL-13Rα2345–354, while HLA-A2−glioma cell lines that express IL-13Rα2345–354could not be recognized by the CTLs. The peptide-specific activity was inhibited by the anti-HLA class I monoclonal antibody. ConclusionsThe induced CTLs specific for the IL-13Rα2345–354peptide could be a potential target of specific immunotherapy for HLA-A2patients with malignant glioma. [ABSTRACT FROM AUTHOR]

Diynes were synthesized in high yields by homocoupling of terminal arylacetylenes and terminal alkylacetylenes in Cu(OAc) 2 ‐PEG (polyethyleneglycol) with NaOAc as a base. Cu(OAc) 2 ‐PEG was readily recycled via solvent precipitation with efficient recyclability. [ABSTRACT FROM AUTHOR]

Spatio-temporal variation of phytoplankton biomass were analyzed for five typical regions in the Yellow Sea (YS) during 2003–2018, using monthly long-term satellite data. The correlation between phytoplankton biomass and physical oceanographic parameters were explored using multiwavelet coherence for each region. The results showed the phytoplankton biomass decreased from the inshore to the center of the YS. There were opposing trends observed for phytoplankton biomass in the coastal area and the middle of the YS. The phytoplankton biomass varied seasonally for five the different regions due to the influence of sea surface temperature (SST), photosynthetically active radiation (PAR), and mix layer depth (MLD). The highest and lowest phytoplankton biomass occurred in April and July in most of regions. The phytoplankton biomass increased in the spring and decreased in winter for all five regions during 2003–2018. The SST, PAR and MLD also increased in most regions during the study periods. The Chlorophyll- a (Chl- a) had an interannual periodicity, mostly influenced by the MLD among the physical oceanographic parameters explored. The Chl- a showed a negative correlation with the SST and the PAR, and a positive correlation with the MLD. Among the physical oceanographic parameters explored, the PAR and the MLD were the key factors that influenced the variation of phytoplankton biomass in the estuary of the Yangtze River (EYR) and the North Yellow Sea (NYS), while the SST and the PAR were the main factors in the Jiangsu Shoal (JSS). In the Yellow Sea Cold Water Mass (YSCWM) and the south coast of Shandong Peninsula (SCSDP), the SST and the MLD were the main factors influencing for the phytoplankton biomass among the physical oceanographic parameters explored, respectively. The best three-factor combination all included Niño 3.4 in each region, which suggest that El Niño had a certain influence on the variation of the Chl- a in the YS over a long time scale. • Phytoplankton biomass in the Yellow Sea was inversely correlated with SST and PAR, and positively correlated with MLD. • MWC can characterize the temporal-scale relationships between phytoplankton biomass and oceanographic parameters. • Combinations of factors that best explained phytoplankton variations were different among regions in the YS. [ABSTRACT FROM AUTHOR]

Heterotopic ossification (HO), often arising in response to traumatic challenges, results from the aberrant osteochondral differentiation of mesenchymal stem cells (MSCs). Nevertheless, the impact of trauma‐induced inflammatory exposure on MSC fate determination remains ambiguous. In this study, the cellular diversity within inflammatory lesions is elucidated, comprising MSCs and several innate and adaptive immune cells. It is observed that quiescent MSCs transition into cycling MSCs, subsequently giving rise to chondrogenic (cMSC) and/or osteogenic (oMSC) lineages within the inflammatory microenvironment following muscle or tendon injuries, as revealed through single‐cell RNA sequencing (scRNA‐seq), spatial transcriptome and lineage tracing analysis. Moreover, these investigations demonstrate that neutrophils and natural killer (NK) cells enhance transition of quiescent MSCs into cycling MSCs, which is also controlled by M1 macrophages, a subpopulation of macrophages can also stimulate cMSC and oMSC production from cycling MSCs. Additionally, M2 macrophages, CD4+ and CD8+ T lymphocytes are found to promote chondrogenesis. Further analysis demonstrates that immune cells promotes the activation of signaling transducers and activators of transcription (STAT) pathway and phosphoinositide 3 (PI3K)/protein kinase B (AKT) pathway in MSC proliferation and osteochondral progenitors' production, respectively. These findings highlight the dynamics of MSC fate within the inflammatory lesion and unveil the molecular landscape of osteoimmunological interactions, which holds promise for advancing HO treatment. [ABSTRACT FROM AUTHOR]

Chitosan (CS) is lack of applications in pharmaceutical industry due to its lower compression density and instability during tablet process. This study mainly focus on the synthesis of ethyl vanillin incorporated CS(EV/CS) via Schiff base reaction and the evaluation of application as pharmaceutic excipient. Results of FT-IR showed that there is a typical amide peak in EV/CS that the 1640 cm−1 can be attributed to –C = N– bond and 1518 cm−1 can be attributed to backbone of benzene but not in CS raw material. Compared with the control, XRD of EV/CS have additional 2θ angle of 44°, 64° and 77° diffraction peaks except that the 2θ = 20° of EV is still existed. More slower weight loss of EV/CS than that of CS in the range of 248–760 °C is also demonstrated by TGA analysis. 1H NMR indicated there are intrinsic 7.5 and 7.1 ppm as well as emerging 4.2 ppm of chemical shift in EV/CS. The physical finger spectra from twelve indexes of EV/CS powder denotes quite differences in compressibility, fluidity and stability with that of CS. 5% content EV/CS of designed formulation can at most decrease the friability and disintegration time of the compressed tablet. In conclusion, the developed EV/CS is inclined to suitable for tablet as an excipient. [ABSTRACT FROM AUTHOR]

The multivariate change point detection problem has been encountered across various fields. Most approaches to this problem assume the series is homogeneous, i.e., all the coordinates change concurrently. Hence, the specific subset of the coordinates containing the change points cannot be determined. In this work, we propose S-MCPD, which is capable of detecting the position of multivariate change points for heterogeneous series by identifying specific coordinates of those changed. Specifically, the problem is discussed in the context of variable selection and transformed into the form of sparse group lasso. In simulation studies, we compared S-MCPD with four existing methods, inspect, sbs, dc, and cpm. The results showed that the performance of S-MCPD was comparable to that of inspect and was superior to other methods in terms of evaluation metrics. In addition, S-MCPD can determine not only the positions of change points, but also the subset of coordinates containing the change points, while other existing methods are unable to achieve this. Moreover, S-MCPD does not depend on the constant variance assumption and works quite well even when the covariance changes, which makes our method more practical. These are the two important contributions of our work. Finally, we applied S-MCPD to two real-world datasets to show its effectiveness. [ABSTRACT FROM AUTHOR]

Proximal sensing offers a novel means for determination of the heavy metal concentration in soil, facilitating low cost and rapid analysis over large areas. In this respect, spectral data and model variables play an important role. Thus far, no attempts have been made to estimate soil heavy metal content using continuum-removal (CR), different preprocessing and statistical methods, and different modeling variables. Considering the adsorption and retention of heavy metals in spectrally active constituents in soil, this study proposes a method for determining low heavy metal concentrations in soil using spectral bands associated with soil organic matter (SOM) and visible–near-infrared (Vis–NIR). To rapidly determine the concentration of heavy metals using hyperspectral data, partial least squares regression (PLSR), principal component regression (PCR), and support vector machine regression (SVMR) statistical methods and 16 preprocessing combinations were developed and explored to determine an optimal combination. The results showed that the multiplicative scatter correction and standard normal variate preprocessing methods evaluated with the second derivative spectral transformation method could accurately determine soil Cr and Ni concentrations. The root-mean-square error (RMSE) values of Vis–NIR model combinations with PLSR, PCR, and SVMR were 0.34, 3.42, and 2.15 for Cr, and 0.07, 1.78, and 1.14 for Ni, respectively. Soil Cr and Ni showed strong spectral responses to the Vis–NIR spectral band. The R2 value of the Vis–NIR-based PLSR model was higher than 0.99, and the RMSE value was 0.07–0.34, suggesting higher stability and accuracy. The results were more accurate for Ni than Cr, and PLSR showed the best performance, followed by SVMR and PCR. This perspective has critical implications for guiding quantitative biogeochemical analysis using proximal sensing data. [ABSTRACT FROM AUTHOR]

Change-point detection for categorical data has wide applications in many fields. Existing methods either are distribution-free, not utilizing categorical information sufficiently, or have limited performance when there exists "rare events" (events that occur with low frequency). In this paper, we propose a Bayesian change-point detection model for categorical data based on Dirichlet-multinomial mixtures. Because of the introduction of prior information, our method performs well for the existence of "rare events". An online parameter estimation procedure and an online detection strategy are then designed to adapt to data streams. Monte Carlo simulations discuss the power of the proposed method and show advantages compared with existing algorithms. Applications in biomedical research, document analysis, health news case study and location monitoring indicate practical values of our method. [ABSTRACT FROM AUTHOR]

Aggregated eutectic intermetallic phases in a casting Mg-Ag-Al alloy were characterized using transmission electron microscopy. Three kinds of intermetallic phases, namely ε-Mg 3 Ag (or ε-Mg 26 − x Ag 7+x), β′-Mg 2 (Al,Ag) 3 , and γ-Mg 17 Al 12 , were observed to aggregate together following certain crystallographic orientation relationships (ORs) as: (001) ε //(1 1 ¯ 2) γ and [100] ε //[110] γ (OR1), (001) ε //(110) γ and [001] ε //[110] γ (OR2), (01 1 ¯) β ′ //(1 ¯ 10) γ and [100] β ′ //[110] γ , and (001) β ′ //(010) ε and [100] β ′ //[100] ε. TEM observations combined with the corresponding phase diagrams reveal that the ε phase firstly formed during solidification, then the γ phase nucleated on the ε phase, and finally, the β′ phase nucleated on the γ phase. This special intermetallic phase composition which owns numerous fine particles and many semi-coherent interphase boundaries results in high-strength and high-ductility for the casting QA61 alloy. Unlabelled Image • Both binary and ternary intermetallic phases were observed in Mg-Ag-Al alloy. • Three aggregated intermetallic phases are semi-coherent with each other. • Two orientation relationships between ε-Mg 3 Ag and γ-Mg 17 Al 12 were revealed. • Mg-6Ag-1Al alloy has high-strength/ductility due to aggregated intermetallic phases. [ABSTRACT FROM AUTHOR]

Aspect-based sentiment analysis (ABSA) aims to conduct fine-grained sentiment analysis, necessitating the extraction of three key components: target entity, aspect category and sentiment polarity. These three components collectively form an integrated ABSA task known as TASD (Target-Aspect-Sentiment jointly Detection). Most of existing approaches on ABSA usually employ Recurrent neural networks(RNNs), Convolutional neural networks(CNNs) or pre-training models such as Bidirectional Encoder Representations from Transformers(BERT). However, they have some common weaknesses. First, most of the existing methods focus on one or two sub-tasks instead of triplet detection, thus they do not establish an end-to-end (training a complex learning system represented by a single model) ABSA model and cannot utilize the relevance of multiple ABSA sub-tasks during training. Second, they cannot achieve accuracy and efficiency simultaneously due to the coupling of context and given aspects. Third, they are poor in recognizing implicit targets. To tackle these limitations, this paper proposes a novel method named the Twin Towers End to End model (TTEE) to solve TASD task. It transforms complex TASD task into a simple end-to-end multi-task framework, simultaneously conducting target and aspect-sentiment detection. It builds twin towers system based on BERT or its updated versions to decouple context and given aspects, which can reduce redundant calculation to improve computational efficiency significantly. It offers great advantage to identify implicit target entity and its associated aspect-sentiment in the context without introducing extra model architecture. Experiments on three public datasets in different domains demonstrate that our approach not only achieves better performance on various evaluation metrics, but also has high efficiency in both training and inference phases, over a wide range of sample size and number of aspect categories. • The T-A-S triplets can be decoded from the end-to-end output of TTEE. • BERT-based model is employed to encode context and aspect-sentiment pairs separately. • TTEE efficiently reduces redundant calculations of embedding process. • TTEE excels in detecting implicit targets within the context. [ABSTRACT FROM AUTHOR]

In recent years, more and more attention has been paid to the construction of rural tourism, and tourists' demand for rural tourism public services has become stronger and stronger. Through the objective and fair evaluation of rural tourism public service performance, on the one hand, it is helpful to improve the overall satisfaction of tourists to rural tourism. On the other hand, it can also ensure the efficiency of public service financial investment and expenditure. Firstly, on the basis of theoretical summary and hierarchical analysis, this paper constructs the performance evaluation index system of rural tourism public service from five aspects of infrastructure services, public transport services, public information services, security services, and public environmental services. Then taking China as an example, the performance of rural tourism public service is evaluated by analytic hierarchy process. The results show that the construction of hard environment such as public transport services, security services, and infrastructure services is a key factor in the construction of rural tourism public services. Finally, according to the evaluation results obtained in this paper, some suggestions are put forward for the development of rural tourism and the improvement of public service quality in the future. [ABSTRACT FROM AUTHOR]

Background: T cell-based immunotherapies are facing great challenges in the recruitment and activation of tumor-specific T cells against solid tumors. Among which, utilizing nanobody (Nb) or nanobodies (Nbs) to construct T cell engager has emerged as a more practical potential for enhancing the anti-tumor effectiveness of T cells. Here, we designed a new Nb-guided multifunctional T cell engager (Nb-MuTE) that not only recruited effector T cells into the tumor tissues, but also efficiently activated T cells anti-tumor immunity when synergies with photothermal effect. Results: The Nb-MuTE, which was constructed based on an indocyanine green (ICG)-containing liposome with surface conjugation of CD105 and CD3 Nbs, and showed excellent targetability to both tumor and T cells, following enhancement of activation, proliferation and cytokine secretion of tumor-specific T cells. Notably, the immunological anti-tumor functions of Nb-MuTE-mediated T cells were further enhanced by the ICG-induced photothermal effect in vitro and in vivo. Conclusions: Such a new platform Nb-MuTE provides a practical and "all-in-one" strategy to potentiate T cell responses for the treatment of solid tumor in clinic. [ABSTRACT FROM AUTHOR]

Influence of 1.5 wt% Nd addition on microstructures and mechanical properties of the as-extruded Mg−6.0Zn–0.5Zr (ZK60) alloy was studied. The results illustrate that Nd addition clearly refines dynamic recrystallized grains but has almost no influence on texture. Additionally, the intermetallic phases were significantly altered by Nd addition. In ZK60 alloy, the coarse intermetallic phases are MgZn 2 , Mg 21 Zn 25 , Mg 4 Zn 7 , MgZn and I-phase, while MgNdZn 3 (W), Mg 43 Zn 51 Nd 6 (T), MgZn 2 and Nd-enriched MgZn after Nd addition. Also, three kinds of new orientation relationships (ORs) between MgZn 2 or its twin domain and Mg were revealed in this work while both MgZn 2 and W were found to be coherent with T following identical ORs. Furthermore, the fine precipitates are with sizes of ∼20 nm and were confirmed as MgZn 2 , MgZn 2 + MgZn and Mg 4 Zn 7 + MgZn 2 in ZK60 alloy while new spherical Guinier Preston (G.P.) zones with sizes of ∼5 nm after Nd addition. Finally, the above microstructural modifications because of Nd addition result in ultra-high strength for ZK60 alloy, with tensile yield strength being approximately 408 MPa. Image 1 • Nd addition clearly refines DRX grains while with almost no effect on texture. • MgZn 2 , Mg 21 Zn 25 , Mg 4 Zn 7 , MgZn and I-phase were revealed in the ZK60 alloy. • W, Mg 43 Zn 51 Nd 6 (T), MgZn 2 , Nd-enriched MgZn and G.P. zones formed after Nd addition. • Three kinds of new ORs between MgZn 2 or its twin domain and Mg were revealed. • The ZK60 + 1.5Nd alloy exhibits high tensile yield strength of approximately 408 MPa. [ABSTRACT FROM AUTHOR]

Abstract Surface plasmon resonance (SPR) biosensors have enormous potential in biological recognitions and biomolecular interactions, especially for the real time measurement of disease diagnosis and drug screening. Extensive efforts have been invested to ameliorate the sensing performances, while the photothermal effects, which are induced by the plasmon resonance, have an obvious impact. However, due to the limitations of experimental approaches, the theoretical mechanisms and specific influences of the SPR sensors with photothermal effects are few researched. Here, a multiscale simulation method is developed to investigate the photothermal effects at graphene/gold (Au) nanointerfaces, and to calculate the quantitative contribution of the photothermal effects towards high reliability SPR sensors in order to elucidate their influence on the sensing performances by means of first-principle calculations and molecular dynamics simulations. Our results indicate that the sensitivity and detection accuracy of graphene/Au SPR sensors can be tailored from 0 K to 600 K, due to the tunable dielectric constants of Au and graphene films through temperature variation. By controlling the its material thickness, interfacial combination and lattice strain, an optimized graphene/Au SPR sensor with higher sensitivity, detection accuracy, and reliability to the temperature rising has been achieved. Such multiscale simulation method, which is capable of seeking both the role and the underlying mechanism of the interfacial phenomena, can serve as an excellent guideline for the performance optimization and commercialized application of SPR sensors in the analytical chemistry and biomedical fields. Highlights • A multiscale simulation method is developed to investigate the quantitative contribution of the photothermal effects towards SPR sensors. • Establish the relationship between the temperatures and dielectric constants of Au and graphene films. • The sensitivity and detection accuracy of graphene/Au SPR sensors can be tailored from 0 K to 600 K. • By controlling the thickness, interfacial combination and lattice strain, an optimized graphene/Au SPR sensor with higher sensitivity, detection accuracy, and reliability to the temperature rising has been achieved. [ABSTRACT FROM AUTHOR]

In the field of nanotechnology, DNA-based nanoscale materials have facilitated the construction of DNA polyhedrons with different shapes and sizes by using predictable base pairing and highly tunable conformation. In this study DNA bipyramid nanostructures with one arm chain (T20-DBNs) were successfully prepared in a single annealing procedure. 99mTc-A20 ssDNA was obtained by radiolabeled DTPA-A20 with 99mTc, and then 99mTc-DTPA-DBNs were obtained by hybridizing T20-DBNs with 99mTc-A20 ssDNA. We focused on studying a method of 99mTc radiolabeling DNA nanostructures with DTPA as a chelate, and hoped to develop a new SPECT molecular imaging probe based on DNA nanostructures. [ABSTRACT FROM AUTHOR]

Background: T cell engagers (TCEs) have been established as an emerging modality for hematologic malignancies, but solid tumors remain refractory. However, the upregulation of programmed cell death 1 (PD-1) is correlated with T cell dysfunction that confer tumor-mediated immunosuppression. Developing a novel nanobody-based trispecific T cell engager (Nb-TriTE) would be a potential strategy to improve therapeutic efficacy. Methods: Given the therapeutic potential of nanobodies (Nbs), we first screened Nb targeting fibroblast activation protein (FAP) and successfully generated a Nb-based bispecific T cell engager (Nb-BiTE) targeting FAP. Then, we developed a Nb-TriTE by fusing an anti-PD-1 Nb to the Nb-BiTE. The biological activity and antitumor efficacy of the Nb-TriTE were evaluated in vitro and in both cell line-derived and patient-derived xenograft mouse models. Results: We had for the first time successfully selected a FAP Nb for the generation of novel Nb-BiTE and Nb-TriTE, which showed good binding ability to their targets. Nb-TriTE not only induced robust tumor antigen-specific killing, potent T cell activation and enhanced T cell function in vitro, but also suppressed tumor growth, improved survival and mediated more T cell infiltration than Nb-BiTE in mouse models of different solid tumors without toxicity. Conclusions: This novel Nb-TriTE provides a promising and universal platform to overcome tumor-mediated immunosuppression and improve patient outcomes in the future. [ABSTRACT FROM AUTHOR]

The emerging Bicycle Sharing System (BSS) provides a new social microscope that allows us to “photograph” the main aspects of the society and to create a comprehensive picture of human mobility behavior in this new medium. BSS has been deployed in many major cities around the world as a short-distance trip supplement for public transportations and private vehicles. A unique value of the bike flow data generated by these BSSs is to understand the human mobility in a short-distance trip. This understanding of the population on short-distance trip is lacking, limiting our capacity in management and operation of BSSs. Many existing operations research and management methods for BSS impose assumptions that emphasize statistical simplicity and homogeneity. Therefore, a deep understanding of the statistical patterns embedded in the bike flow data is an urgent and overriding issue to inform decision-makings for a variety of problems including traffic prediction, station placement, bike reallocation, and anomaly detection. In this paper, we aim to conduct a comprehensive analysis of the bike flow data using two large datasets collected in Chicago and Hangzhou over months. Our analysis reveals intrinsic structures of the bike flow data and regularities in both spatial and temporal scales such as a community structure and a taxonomy of the eigen-bike-flows. [ABSTRACT FROM AUTHOR]

Aminoglycoside antibiotics (AGAs) are widely used in life-threatening infections, but they accumulate in cochlear hair cells (HCs) and result in hearing loss. Increases in adenosine triphosphate (ATP) concentrations and P2X7 receptor expression were observed after neomycin treatment. Here, we demonstrated that P2X7 receptor, which is a non-selective cation channel that is activated by high ATP concentrations, may participate in the process through which AGAs enter hair cells. Using transgenic knockout mice, we found that P2X7 receptor deficiency protects HCs against neomycin-induced injury in vitro and in vivo. Subsequently, we used fluorescent gentamicin–Fluor 594 to study the uptake of AGAs and found fluorescence labeling in wild-type mice but not in P2rx7−/− mice in vitro. In addition, knocking-out P2rx7 did not significantly alter the HC count and auditory signal transduction, but it did inhibit mitochondria-dependent oxidative stress and apoptosis in the cochlea after neomycin exposure. We thus conclude that the P2X7 receptor may be linked to the entry of AGAs into HCs and is likely to be a therapeutic target for auditory HC protection. Schematic of the role of P2X7 receptor in neomycin-induced HC loss. Under physiological control conditions, P2X7 receptor acts as a channel. ATP and small molecules can pass through it, while large molecules cannot. After neomycin exposure, large amounts of ATP are released from cells and the extracellular concentration of ATP increases rapidly. In addition, more P2X7 receptors are synthesized and appear in the membrane. The high concentrations of ATP cause P2X7 receptor to open as a pore that is large enough for neomycin to enter the HCs, thus damaging the HCs and causing apoptosis. [Display omitted] • AGAs induced cochlear HC damage is associated with changes in eATP concentration and P2X7 receptor activation. • P2X7 receptor is involved to AGAs uptake in HCs. • AGAs-related mitochondria-mediated oxidative stress could be abolished by deleting P2rx7. • P2X7 receptor might be a new target for HC protection from AGAs. [ABSTRACT FROM AUTHOR]

Nanobodies (Nbs) are the variable domain of heavy‐chain antibodies derived from the blood of camelids or sharks. Nanobodies are the smallest antibody fragment with intact antigen‐binding ability. Compared to conventional antibodies, nanobodies have unique properties such as small size, excellent stability and solubility, low immunogenicity, ability to recognize hidden epitopes, high tissue penetration, and industrialized production. More excitingly, the camelid‐specific amino acid sequences in the framework are mutated to their human heavy‐chain variable domain equivalent, which is humanized, to a wide range of applications. These superior characteristics make nanobody an ideal alternative to conventional antibody, showing excellent prospects for various applications in structural biology, molecular imaging, disease diagnosis and therapy, agricultural products, and environmental chemicals detection. With the continuous updating of theories and the rapid development of technology, the screening and expression methods of nanobodies are increasingly mature. Consequently, several technologies to identify and express nanobodies have been established, and various use cases have been described. In this review, we summarize recent advances in the discovery and production of novel nanobodies, and their use in detection and diagnosis platforms. [ABSTRACT FROM AUTHOR]

In this article, we propose a focused information criterion (FIC) and develop a frequentist model averaging estimation procedure for a partial linear regression model when the response is randomly right-censored. The proposed procedure is based on the quantile regression and can depict the comprehensive character of the distribution of the response by means of modeling different quantiles. The large sample properties of the proposed estimators are established, and their finite sample properties are examined through simulation studies. An application to a primary biliary cirrhosis data set is provided. [ABSTRACT FROM AUTHOR]

The recently proposed Reinforced Multicategory Support Vector Machine (RMSVM) has been proven to have desirable theoretical properties as well as competitive numerical accuracy for multi-class classification problems. Currently solving the RMSVM is based on a grid search approach for selecting the tuning parameter [ABSTRACT FROM AUTHOR]

Background & Aims In this study, we investigated the role of salt-inducible kinase 1 (SIK1) and its possible mechanisms in human hepatocellular carcinoma (HCC). Methods Immunoprecipitation, immunohistochemistry, luciferase reporter, Chromatin immunoprecipitation, in vitro kinase assays and a mouse model were used to examine the role of SIK1 on the β-catenin signaling pathway. Results SIK1 was significantly downregulated in HCC compared with normal controls. Its introduction in HCC cells markedly suppresses epithelial-to-mesenchymal transition (EMT), tumor growth and lung metastasis in xenograft tumor models. The effect of SIK1 on tumor development occurs at least partially through regulation of β-catenin, as evidenced by the fact that SIK1 overexpression leads to repression of β-catenin transcriptional activity, while SIK1 depletion has the opposite effect. Mechanistically, SIK1 phosphorylates the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) at threonine (T)1391, which promotes the association of nuclear receptor corepressor (NCoR)/SMRT with transducin-beta-like protein 1 (TBL1)/transducing-beta-like 1 X-linked receptor 1 (TBLR1) and disrupts the binding of β-catenin to the TBL1/TBLR1 complex, thereby inactivating the Wnt/β-catenin pathway. However, SMRT-T1391A reverses the phenotype of SIK1 and promotes β-catenin transactivation. Twist1 is identified as a critical factor downstream of SIK1/β-catenin axis, and Twist1 knockdown (Twist1 KD ) reverses SIK1 KD -mediated changes, whereas SIK1 KD /Twist1 KD double knockdown cells were less efficient in establishing tumor growth and metastasis than SIK1 KD cells. The promoter activity of SIK1 were negatively regulated by Twist1, indicating that a double-negative feedback loop exists. Importantly, levels of SIK1 inversely correlate with Twist1 expression in human HCC specimens. Conclusions Our findings highlight the critical roles of SIK1 and its targets in the regulation of HCC development and provides potential new candidates for HCC therapy. [ABSTRACT FROM AUTHOR]

• 1. IL-6 central to OME, affects NLP pathways and inflammation. • 2. IL-6 mAb and NF-kB inhibitor reduce IL-6 and CXCL1 in OME models. • 3. IL-6 balances Th17 and Th1/Th2 in OME pathogenesis. • 4. Insights into OME immune mechanisms suggest new treatments. Otitis media with effusion (OME) often leads to pediatric hearing loss and is influenced by innate and adaptive immune responses. Innate immunity serves as the non-specific first line of defense against OME. We induced OME in rats using ovalbumin. We administered IL-6 monoclonal antibodies intranasally to inhibit IL-6, and we injected an NF-κB inhibitor intraperitoneally to explore the role of IL-6 in innate immunity and its interaction with the NOD-like receptor signaling pathway. We analyzed RNA-sequencing data with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways to assess signaling pathways involved in OME. We also utilized Western blot, quantitative real-time PCR, and immunohistochemistry on middle ear samples and used microscopy to identify immune cells in ear wash fluids. Our study suggests a pivotal role for IL-6 in the immune pathways of rats with OME via the regulation of CXCL1-mediated pathways. Increased levels of IL-6 and CXCL1 were observed in the middle ear tissues, and activation of the NLRP3 inflammasome in OME rats led to an immune response via NF-κB, thus promoting IL-6 and CXCL1 production, which was reduced by IL-6 antibody treatment. Our findings confirm that IL-6 and CXCL1 play significant roles in the innate immune response in OME in rodents, predominantly via the NOD-like receptor signaling pathway and NLRP3 inflammasome activation. This research sheds light on OME pathogenesis and its immune-related mechanisms. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an infectious disease that has become a serious burden on global public health. This study screened and yielded specific nanobodies (Nbs) against SARS-CoV-2 spike protein receptor binding domain (RBD), following testing its basic characteristics. A nanobody phage library was established by immunizing a camel with RBD protein. After three rounds of panning, the positive colonies were screened by enzyme-linked immunosorbent assay (ELISA). By sequencing, four different sequences of nanobody gene fragments were selected. The four nanobody fusion proteins were expressed and purified, respectively. The specificity and affinity of the four nanobodies were identified by ELISA. Our results showed that an immune phage display library against SARS-CoV-2 has been successfully constructed with a library capacity of which was 4.7 × 108 CFU. The four purified nanobodies showed specific high-affinity binding SARS-CoV-2 S-RBD. Among these, the antigen binding affinity of Nb61 was more comparable to that of commercial rabbit anti-SARS-CoV-2 S-RBD antibodies. In sum, our study has obtained four nanobody strains against SARS-CoV-2 S-RBD with significant affinity and specificity, therefore laying an essential foundation for further research as well as the applications of diagnostic and therapeutic tools of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The present study is to explore the anticancer effect of loonamycin (LM) in vitro and in vivo, and investigate the underlying mechanism with combined multi-omics. LM exhibited anticancer activity in human triple negative breast cancer cells by promoting cell apoptosis. LM administration inhibited the growth of MDA-MB-468 tumors in a murine xenograft model of breast cancer. Mechanistic studies suggested that LM could inhibit the topoisomerase I in a dose-dependent manner in vitro experiments. Combined with the transcriptomics and proteomic analysis, LM has a significant effect on O-glycan, p53-related signal pathway and EGFR/PI3K/AKT/mTOR signal pathway in enrichment of the KEGG pathway. The GSEA data also suggests that the TNBC cells treated with LM may be regulated by p53, O-glycan and EGFR/PI3K/AKT/mTOR signaling pathway. Taken together, our findings predicted that LM may target p53 and EGFR/PI3K/AKT/mTOR signaling pathway, inhibiting topoisomerase to exhibit its anticancer effect. [ABSTRACT FROM AUTHOR]

Background: The inner ear organ is a delicate tissue consisting of hair cells (HCs) and supporting cells (SCs).The mammalian inner ear HCs are terminally differentiated cells that cannot spontaneously regenerate in adults. Epithelial non‐hair cells (ENHCs) in the utricle include HC progenitors and SCs, and the progenitors share similar characteristics with SCs in the neonatal inner ear. Methods: We applied single‐cell sequencing to whole mouse utricles from the neonatal period to adulthood, including samples from postnatal day (P)2, P7 and P30 mice. Furthermore, using transgenic mice and immunostaining, we traced the source of new HC generation. Results: We identified several sensory epithelial cell clusters and further found that new HCs arose mainly through differentiation from Sox9+ progenitor cells and that only a few cells were produced by mitotic proliferation in both neonatal and adult mouse utricles. In addition, we identified the proliferative cells using the marker UbcH10 and demonstrated that in adulthood the mitotically generated HCs were primarily found in the extrastriola. Moreover, we observed that not only Type II, but also Type I HCs could be regenerated by either mitotic cell proliferation or progenitor cell differentiation. Conclusions: Overall, our findings expand our understanding of ENHC cell fate and the characteristics of the vestibular organs in mammals over the course of development. [ABSTRACT FROM AUTHOR]