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This study used accelerometers and hydrophones to measure the vibration and underwater noise from two different types of offshore wind turbine installed near the East China Sea Bridge (Shanghai). Wind speed and rotor speed were also monitored synchronously. The spectrograms of the vibration and underwater noise signals display well-defined spectral lines that are easily distinguishable. Line-component spectra of both vibration and underwater noise signals were synchronously extracted through filtering and correlation analysis. On this basis, relationships between the intensity and frequency of wind turbine vibration and underwater noise line-component spectra, rotor speed, and wind speed were analyzed. Results indicate that rotor speed is positively correlated with wind speed, and that the peak vibration frequencies and intensities of both types of turbine are positively correlated with rotor speed. Consequently, it can be concluded that the frequency and intensity of turbine-generated underwater noise are closely related to wind speed. Additionally, the vibration mechanism and the characterization of underwater noise of the wind turbines have been revealed. [ABSTRACT FROM AUTHOR]

The melting of micro/nanoparticles considering the Soret effect in an alloy melt is studied in terms of the asymptotic method. The results reveal that the positive Soret coefficient weakens the dynamic disequilibrium near the interface, and then enhances the melting temperature of the particle and decreases the melting speed of the particle. The negative Soret coefficient strengthens the dynamic disequilibrium near the interface, and then reduces the melting temperature of the particle and increases the melting speed of the particle. The positive Soret coefficient weakens the accumulation of the solute flux near the interface and enhances the solute concentration. The negative Soret coefficient strengthens the accumulation of the solute flux near the interface and reduces the solute concentration. The size dependence of the melting temperature considering the Soret coefficient is quantitatively consistent with the experimental data, especially for the micro/nanoparticles with a radius smaller than 5 nm. [ABSTRACT FROM AUTHOR]

Objective: We investigated the characteristics and factors influencing eye emotion recognition in self‐limited epilepsy patients with centrotemporal spikes (SeLECTS) complicated with electrical status epilepticus during sleep (ESES). Methods: We selected SeLECTS (n = 160) patients treated in the outpatient and inpatient departments of Anhui Children's Hospital from September 2020 to January 2022. According to the video electroencephalogram monitoring slow‐wave index (SWI), SeLECTS patients with SWI < 50% were assigned into the typical SeLECTS group (n = 79), and patients with SWI ≥ 50% were assigned into the ESES group (n = 81). Patients in the two groups were assessed by The Eye Basic Emotion Discrimination Task (EBEDT) and The Eye Complex Emotion Discrimination Task (ECEDT), respectively. Comparisons were made with age‐, sex‐ and education level‐matched healthy control participants. The correlation between the characteristics of emotional discrimination disorder in the eye area and the clinical influencing factors was analyzed in ESES group, and p ≤.050 was the threshold for significance. Results: Relative to the healthy control group, scores of sadness and fear in the typical SeLECTS group were markedly lower (p =.018, p =.023), while differences in scores of disgust, happiness, surprise, and anger were not significantly different between the groups (p =.072, p =.162, p =.395, p =.380, respectively). Compared with the healthy control group, the ESES group had significantly low scores in recognition of sadness, fear, disgust, and surprise (p =.006, p =.016, p =.043 and p =.038, respectively). However, differences in recognition of happiness and anger between the groups were not significant (p =.665 and p =.272). Univariate logistic analysis showed that the score of eye recognition for sadness in the ESES group was affected by age of onset, SWI, ESES duration and number of seizures. The score of eye recognition for fear was mainly affected by SWI, while the score of eye recognition for disgust was affected by SWI and number of seizures. The surprised eye emotion recognition score was mainly affected by the number of seizures. Variables with p <.1 were considered to be independent variables of multivariable ordered logistic regression. Multivariate logistic analysis showed that sadness emotion recognition was mainly affected by SWI and ESES duration, while disgust was mainly affected by SWI. Conclusion: The typical SeLECTS group showed impaired emotion (sadness and fear) recognition function in the eye area. The ESES group was associated with more intense emotional (sadness, fear, disgust, and surprise) recognition impairment in the eye region. The higher the SWI, the younger the onset age and the longer the duration of ESES, while the more the number of seizures, the more serious the impairment of emotional recognition function in the affected eye area. [ABSTRACT FROM AUTHOR]

Dess–Martin periodinane (DMP) is a broadly applicable oxidant in chemical synthesis. In this work, an efficient and convenient synthesis of N-substituted isoquinolinone derivatives mediated by DMP was achieved through the oxidative coupling reaction of functionalized isoquinoline with readily available benzyl bromide, which is a metal-free, mild, and practical method for synthesizing isoquinoline-1,3-dione or isoquinoline-1,3,4-trione derivatives in excellent yields. The H2O18-labeling experiment was performed to gain insight into the possible mechanism for this reaction. [ABSTRACT FROM AUTHOR]

This study aims to quantitatively analyze the three-dimensional microstructure of ultra-thin HDF paving boards and molding boards, in order to explore the modeling methods of HDF and attempt to predict its mechanical properties more accurately through theoretical and simulation analyses. In this study, non-destructive analysis of the internal microstructure was conducted using computed tomography (CT) imaging technology. The characteristics of microstructural evolution during the hot compression molding process were explored, and all analyzed data were utilized for 3D reconstruction and simulation model construction. Ultra-thin fiberboards with different fiber ratios were modeled through volume compression and experimentally simulated in tension. The results were compared with experimentally determined results for verification purposes. Additionally, differences in surface roughness, water absorption, and expansion of ultra-thin fiberboards with varying fiber ratios were analyzed. The findings indicate that different fiber ratios have a significant impact on the mechanical properties of ultra-thin fiberboards; tensile strength increases with an increase in medium-length fibers content when fibers are pulled or split, highlighting the key role played by the strength of the fibers themselves. Furthermore, it was observed that surface roughness and water-absorbing expansion rate are lower when a higher proportion of fine fibers is present. The results from this study hold great significance for gaining a deeper understanding of the composition, structure, and properties of ultra-thin fiberboards as well as exploring modeling methods for high-density fiberboards. They also provide guidance for optimizing material formulations and preparation processes while improving performance and quality standards for poplar-ultra-thin fiberboards. • We quantitatively analysed the three-dimensional microstructure of ultra-thin fibreboard paving slabs and moulded panels. • We explored the modelling method of high-density fibreboard and obtained a model of high-density fibreboard with a volume fraction of 90%. • We explored the effects of different fibre ratios on the mechanical properties of ultra-thin fibreboards. [ABSTRACT FROM AUTHOR]

Estrogen receptor (ER) is a major transcriptional regulator that plays an important role in the treatment of breast cancer. Herein, we rationally designed and synthesized a novel small-molecule near-infrared (NIR) fluorescent probe, 2-(4-(2-(2,5-bis(2-fluoro-4-hydroxyphenyl)thiophen-3-yl)vinyl)− 3-cyano-5,5-dimethylfuran-2(5 H)ylidene)malononitrile (TCFT) , which could enable prolonged live-cell imaging by three-dimensional (3D) confocal microscopy. Moreover, this bifunctional probe also exhibited photostability, selective estrogen receptor modulator activity, and potent antiproliferative activity for targeted breast cancer therapy, which would be a prominent NIR fluorescent probe for breast cancer study. [Display omitted] • A novel photostable NIR fluorescent probe TCFT was developed for estrogen receptor. • TCFT was successfully applied in prolong live-cell imaging of estrogen receptor by 3D confocal microscopy. • TCFT exhibited selective estrogen receptor modulator activity and potent antiproliferative activity for breast cancer therapy. • TCFT possessed the potential as a theranostic probe for estrogen receptor (+) breast cancer study. [ABSTRACT FROM AUTHOR]

Human peripheral blood mononuclear cells (PBMCs) originate from hematopoietic stem cells in the bone marrow, which mainly includes lymphocytes (T cells, B cells, and natural killer cells) and monocytes. Cryopreserved PBMCs providing biobank resources are crucial for clinical application or scientific research. Here, we used flow cytometry to explore the influence of long-term cryopreservation on the quality of PBMCs with the aim of providing important evidence for the effective utilization of biobank resources. The PBMCs were isolated from the peripheral blood, which was collected from volunteers in the hospital. After long-term cryopreservation in liquid nitrogen, we analyzed the changes in cell numbers, viability, and multiple subtypes of PBMCs and studied the apoptosis, proliferation, activation, function, and status of T cells in comparison with freshly isolated PBMCs by flow cytometry, and then further tracked the effects of long-term cryopreservation on the same sample. Although the different cell types in the PBMCs dynamically changed compared with those in the freshly isolated samples, PBMC recovery and viability remained stable after long-term cryopreservation, and the number of most innate immune cells (e.g., monocytes and B cells) was significantly reduced compared to that of the freshly isolated PBMCs or long-term cryopreserved PBMCs; more importantly, the proportion of T cell subtypes, apoptosis, proliferation, and functional T cells, except for Tregs, were not affected by long-term cryopreservation. However, the proportions of activated T, naïve T, central memory T, effector T, and effector memory T cells dynamically changed after long-term cryopreservation. This article provides important evidence for the effective utilization of biobank resources. Long-term cryopreserved PBMCs can be partly used as biological resources for clinical research or basic studies, but the effect of cryopreservation on PBMCs should be considered when selecting cell samples, especially in research relating to activating or inhibiting function. [ABSTRACT FROM AUTHOR]

Relapsed and refractory (R/R) mantle cell lymphoma (MCL) remains an incurable lymphoma with a poor prognosis. Recently, there are a few studies demonstrating the efficacy of anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy in MCL, including ZUMA-2 study in which CD28-based CAR-T cells were used. However, long-term efficacy and safety associated with 4-1BB-based CAR-T therapy in MCL are not defined well. Here, we report three male patients with R/R classical MCL, who received CD19-directed 4-1BB CAR-T therapy and achieved complete remission, showed mild symptoms of cytokine-release syndrome (CRS) and had no neurological toxicity. During a follow-up of 24– 35 months, all three patients remained in complete remission. Persistent B-cell depletion was observed in two patients. Recovery of CD19+ polyclonal B cells was detected in one patient at 6 months after CAR-T cell infusion. Recovery of serum immunoglobulin, including IgG, IgA and IgM, was not observed in two patients at the last follow-up. Only one patient developed herpes zoster, and the other two patients had no serious infection. This is the first report about the efficacy, long-term remission and safety of CD19-directed 4-1BB CAR-T therapy in R/R MCL. [ABSTRACT FROM AUTHOR]

Purpose: Diffuse large B cell lymphoma (DLBCL) is an aggressive B-cell malignancy with clinical and molecular heterogeneity whose genetics may have clinical implications for patient stratification and treatment. The circulating tumor DNA (ctDNA) is a novel noninvasive, real-time, and tumor-specific biomarker harboring tumor-derived genetic alterations that are identical to those of tumor cells, thus showing great promise in individualized medicine, including precise diagnosis, prediction of prognosis, response monitoring, and relapse detection for DLBCL. Patients and Methods: In this study, we applied NGS analysis to tumor biopsies and ctDNA samples from 16 DLBCL subjects. Then, we compared the genomic alterations from 41 newly diagnosed patients and 56 relapsed/refractory (R/R) patients. Results: Our results show that ctDNA can function as a liquid biopsy for tracking recurrently mutated genes in DLBCL (sensitivity: 87.50%). The mutational profiles of newly diagnosed and R/R DLBCL groups largely overlapped, but the frequencies of some gene mutations differ between the two cohorts. The distribution of mutations also revealed different frequencies in the two cohorts due to different signaling pathways. Genes from apoptosis pathway, immune response and BCR pathway suffered more mutations in R/R patients. Conclusion: Overall, this study establishes ctDNA as an easily accessible source of tumor DNA for DLBCL genotyping and provides a deeper understanding of the somatic alteration spectrum for both newly diagnosed and R/R DLBCL patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate diagnostic performance of radiomics models of MRI in the detection of differentiation degree (DD) and lymph node metastases (LNM) of extrahepatic cholangiocarcinoma (ECC). We retrospectively enrolled 100 patients with ECC confirmed by pathology from January 2011 to December 2018. Three hundred radiomics features were extracted from each region of interest using MaZda software. Next, the radiomics model was developed by incorporating the optimal radiomics signatures and ADC values of tumors to predict DD (model A) and LNM (model B) of ECC, respectively, through the random forest algorithm. After which, the performance of the radiomics models were further evaluated. The model A showed better performance in both training and testing cohorts to discriminate high and medium-low differentiation groups of ECC, with an average AUC of 0.78 and 0.80, respectively. The model B also yielded the good average AUC of 0.80 and 0.90 to predict the LNM of ECC in training and testing cohorts. The radiomics models based on MRI performed well in predicting DD and LNM of ECC and have significant potential in clinical noninvasive diagnosis and in the prediction of ECC. [ABSTRACT FROM AUTHOR]

The conventional theory of crystal growth presents an irreversible outward increase of the crystal size through solute deposition on the nuclei; however, the asymptotic solution of the dynamics model of the particle reveals that the crystal growth undergoes a locally reversible inward growth process in the early stage of crystal growth. Immediately after nucleation, some parts of the interface first grow inward through solute rejection along certain crystal orientations from the interface of nucleation, while the other parts of the interface grow outward through solute deposition along other crystal orientations. Until the inward growth attains a certain distance, the interface grows outward along each crystal orientation. This growth behavior is attributed to the interaction between interface morphology of particles with the anisotropic effect of interface kinetics. Through a systematic variation of the anisotropy parameters, the particle exhibits a continuous transition from one growth morphology to other growth morphologies. During the morphological transition process, as initial concentration increases, the growth of the particle is inhibited in the preferred growth directions, whereas it is facilitated in other growth directions. As a result, the interface morphologies of the particle with different petal‐shaped morphologies in the early stage of crystal growth are formed. [ABSTRACT FROM AUTHOR]

Background: Most cases of extrahepatic cholangiocarcinoma (ECC) show various degrees of hyperintensity on diffusion-weighted imaging (DWI) and hypointensity on apparent diffusion coefficient (ADC). However, the factors influencing ADC values in ECC have not yet been explored extensively. Therefore, this study explored the independent factors influencing ADC values in ECC.Methods: A total of 88 patients with ECC confirmed by surgical pathology were retrospectively assessed. All patients underwent abdominal magnetic resonance imaging (MRI) at 3.0 T and ADC values of the tumor were measured. The correlation between ADC values and multiple clinicopathological features in ECC was analyzed, and independent factors influencing the ADC values in ECC were explored further.Results: The ADC value of the tumor showed a significant difference in different perineural invasion group (p = 0.048), microvascular invasion group (p = 0.001), vascular endothelial growth factor expression group (p < 0.001), lymphatic status group (p = 0.003), and differentiation degree (DD) group (p < 0.001). However, there were no significant differences in different sex (p = 0.715), tumor location (p = 0.659), and degree of T stage (p = 0.879). Moreover, ADC value was negatively correlated with microvascular density (r = -0.725, p < 0.001) and lesion size (r = -0.244, p = 0.023). Nevertheless, there was no correlation between ADC value and patient age (r = 0.026, p = 0.812). Further regression analysis indicated that ADC value was independently associated with pathological DD of ECC (R2 = 0.678, p < 0.001) but not with other clinicopathological factors (p > 0.05).Conclusion: ADC value of ECC is independently correlated with pathological DD of ECC, indicating that ADC value is a potential imaging biomarker for predicting the degree of ECC malignancy. [ABSTRACT FROM AUTHOR]

Tumor vasculature is characterized by aberrant structure and function, resulting in immune suppressive profiles of tumor microenvironment (TME) through limiting immune cell infiltration into tumors. The defective vascular perfusion in tumors also impairs the delivery and efficacy of chemotherapeutic agents. Targeting abnormal tumor blood vessels has emerged as an effective therapeutic strategy to improve the outcome of chemotherapy and immunotherapy. In this study, we demonstrated that Salvianolic acid B (SalB), one of the major ingredients of Salvia miltiorriza elicited vascular normalization in the mouse models of breast cancer, contributing to improved delivery and response of chemotherapeutic agent cisplatin as well as attenuated metastasis. Moreover, SalB in combination with anti-PD-L1 blockade retarded tumor growth, which was mainly due to elevated infiltration of immune effector cells and boosted delivery of anti-PD-L1 into tumors. Mechanistically, tumor cell enhancer of zeste homolog 2 (Ezh2)-driven cytokines disrupted the endothelial junctions with diminished VE-cadherin expression, which could be rescued in the presence of SalB. The restored vascular integrity by SalB via modulating the interactions between tumor cells and endothelial cells (ECs) offered a principal route for achieving vascular normalization. Taken together, our data elucidated that SalB enhanced sensitivity of tumor cells to chemotherapy and immunotherapy through triggering tumor vascular normalization, providing a potential therapeutic strategy of combining SalB and chemotherapy or immunotherapy for patients with breast cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

The direct-global-matrix coupled-mode model (DGMCM) for sound propagation in range-dependent waveguides was recently developed by Luo et al. [A numerically stable coupled-mode formulation for acoustic propagation in range-dependent waveguides, Sci. China G: Phys. Mech. Astron. 55 (2012) 572-588]. A brief review of the formulation and characteristics of this model is given. This paper extends this model to deal with realistic problems involving an inhomogeneous water column and a penetrable sloping bottom. To this end, the normal mode model KRAKEN is adopted to provide local modal solutions and their associated coupling matrices. As a result, the extended DGMCM model is capable of providing full two-way solutions to two-dimensional (2D) realistic problems with a depth- and range-dependent sound speed profile as well as a penetrable sloping bottom. To validate this model, it is first applied to a benchmark problem of sound propagation in a plane-parallel waveguide with a depth- and range-dependent sound speed profile, and then it is applied to a problem involving both an inhomogeneous water column and a sloping bottom. Comparisons with the analytical solution proposed by DeSanto and with the numerical model COUPLE are also provided, which show that the extended DGMCM model is accurate and efficient and hence can serve as a benchmark for realistic problems of sound propagation in an inhomogeneous waveguide. [ABSTRACT FROM AUTHOR]

Titanium nitride nanoparticles (TiN NPs) are proposed as a novel catalyst towards the V(II)/V(III) redox pair for the negative electrode in vanadium redox flow batteries (VRFB). Electrochemical properties of TiN NPs were characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The results show that TiN NPs demonstrate better electrochemical activity and reversibility for the processes of V(II)/V(III) redox couples as compared with the graphite NPs. TiN NPs facilitate the charge transfer in the V(II)/V(III) redox reaction. Performance of a VRFB using a TiN NPs coated carbon paper as a negative electrode is much higher than that of a VRFB with a raw carbon paper electrode. The columbic efficiency (CE), the voltage efficiency (VE) and the energy efficiency (EE) of the VRFB single cell at charge-discharge current density of 30 mA/cm 2 are 91.74%, 89.11% and 81.74%, respectively. During a 50 charge-discharge cycles test, the CE values of VRFB with TiN NPs consistently remain higher than 90%. [ABSTRACT FROM AUTHOR]

[Display omitted] • Graphene induced conformation changes of SARS-CoV-2 spike RBD are studied by MD simulations. • Graphene significantly affects the secondary structure of the three key sites binding with ACE2. • Both π–π stacking and hydrophobic interactions orchestrate RBD adsorption. • To develop graphene-based protective equipments to defeat SARS-CoV-2 is possible. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread in the world, causing more than two million deaths and seriously threatening human life. Effective protection measures are important to prevent the infection and spreading of the virus. To explore the effects of graphene on the virus adsorption and its biological properties, the adsorption process of the receptor binding domain (RBD) of SARS-CoV-2 on graphene has been investigated by molecular dynamics simulations in this paper. The results show that RBD can be quickly adsorbed onto the surface of graphene due to π - π stacking and hydrophobic interactions. Residue PHE486 with benzene ring has stronger adsorption force and the maximum contact area with graphene. Graphene significantly affects the secondary structure of RBD area, especially on the three key sites of binding with human ACE2, GLY476, PHE486 and ASN487. The binding free energy of RBD and graphene shows that the adsorption is irreversible. Undoubtedly, these changes will inevitably affect the pathogenicity of the virus. Therefore, this study provides a theoretical basis for the application of graphene in the protection of SARS-CoV-2, and also provides a reference for the potential application of graphene in the biomedical field. [ABSTRACT FROM AUTHOR]

A coupled-mode model is a classic approach for solving range-dependent sound propagations and is often used to provide benchmark solutions in comparison with other numerical models because of its high accuracy. Existing coupled-mode programs have disadvantages such as high computational cost, weak adaptability to complex ocean environments, and numerical instability. In this paper, a new algorithm that uses an improved range normalization of a "stair-step" and global matrix approach to address range dependence in ocean environments is designed. This algorithm uses the Chebyshev–Tau spectral method to solve the eigenpairs in the range-independent segments. The Chebyshev–Tau spectral method can converge rapidly, and the rate of convergence depends on the smoothness of the sound speed and density profiles. The main steps of the algorithm are parallelized, so parallel computing technologies are also applied for further acceleration. Based on this algorithm, an efficient program is implemented, and numerical simulations verify that this algorithm is reliable, accurate, and capable. Compared with the existing coupled-mode programs, the newly developed program is more stable and efficient with comparable accuracy and can simulate waveguides in more complex and realistic ocean environments. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fe 3 O 4 Fe 3 O 4 with small particles was compounded with BiOBr/BiOI(3:1) by solvothermal method. • The magnetism of Fe 3 O 4 /BiOBr/BiOI (1.1:3:1) is larger than that of previous studies. • Fe 3 O 4 /BiOBr/BiOI (1.1:3:1) exhibits good adsorption capacity and photocatalytic performance. • Fe 3 O 4 /BiOBr/BiOI (1.1:3:1) presents excellent recyclability and stability. Ternary magnetic Fe 3 O 4 /BiOBr/BiOI (1.1:3:1) with good magnetic separation performance and photocatalytic degradation performance was synthesized by two-step method. These properties remained good after repeated use for 10 times. Compared with Fe 3 O 4 /BiOBr/BiOI (0.5:2:2) prepared by other research group, the magnetism Fe 3 O 4 /BiOBr/BiOI (1.1:3:1) were 1.76 times that of it. Compared with the previous work, Fe 3 O 4 /BiOBr/BiOI (1.1:3:1) has advantages in magnetism, degradation activity and reusability. All results suggested that the Fe 3 O 4 /BiOBr/BiOI (1.1:3:1) with good photocatalytic performance, good magnetic separability, excellent recyclability, and stability has a good application prospect in photocatalytic degradation organic wastewater. [ABSTRACT FROM AUTHOR]

Abstract: Through structure-based virtual screening, some dozen of benzene sulfonamides with novel scaffolds are identified as potent inhibitors against carbonic anhydrase (CA) IX with IC50 values ranging from 2.86 to 588.34nM. Among them, compounds 1 and 9 show high selectivity against tumor-target CA IX over CA II (the selectivity ratios are 21.3 and 136.6, respectively). The possible binding poses of hit compounds are also explored and the selectivity is elucidated by molecular docking simulations. The hit compounds discovered in this work would provide novel scaffolds for further hit-to-lead optimization. [Copyright &y& Elsevier]

The role of B cells in cancer and the underlying mechanisms remain to be further explored. Here, we show that tumor-associated B cells with activated STAT3 contribute to tumor development by promoting tumor angiogenesis. B cells with or without Stat3 have opposite effects on tumor growth and tumor angiogenesis in both B16 melanoma and Lewis Lung Cancer mouse models. Ex vivo angiogenesis assays show that B cell-mediated tumor angiogenesis is mainly dependent on the induction of pro-angiogenic gene expression, which requires Stat3 signaling in B cells. Furthermore, B cells with activated STAT3 are mainly found in or near tumor vasculature and correlate significantly with overall STAT3 activity in human tumors. Moreover, the density of B cells in human tumor tissues correlates significantly with expression levels of several STAT3-downstream pro-angiogenic genes, as well as the degree of tumor angiogenesis. Together, these findings define a novel role of B cells in promoting tumor progression through angiogenesis and identify STAT3 in B cells as potential therapeutic target for anti-angiogenesis therapy. [ABSTRACT FROM AUTHOR]

The growth of precipitates in a solution system is studied using the asymptotic method, taking into account the cross diffusion between solutes. The resulting asymptotic solution for the dynamic model of the precipitate growing in the solution reveals that the concentration distribution is significantly changed by the cross diffusion between solutes and the growth of precipitate depends not only on the self diffusion of solutes, but also on the diffusive interaction between solutes. The attractive diffusive interaction between solutes in the solution enhances the solute diffusion and facilitates the growth of precipitate, whereas the repulsive diffusive interaction between solutes depresses the solute diffusion and inhibits the growth of precipitate. [ABSTRACT FROM AUTHOR]

Involvement of phosphatidylinositol 3-kinase/Akt-1 in cell survival and proliferation of multiple myeloma (MM) has been well established. In this study, we demonstrate that homoharringtonine (HHT), an antileukemic drug first isolated from the Chinese evergreen Cephalotaxus harringtonia, induces significant cytotoxicity in dexamethasone-sensitive and -resistant and chemotherapy-sensitive MM cell lines in a time and dose-dependent manner. HHT also triggers apoptosis in chemotherapy-resistant patient's myeloma cells. Contrary to dexamethasone, the cytotoxicity of HHT on myeloma is independent of interleukin-6. The mechanism of HHT cytotoxicity is related to down-regulation of Akt phosphorylation/activation and various target genes of Akt including nuclear factor κ B, XIAP, cIAP and cyclin D1. Moreover, in vivo antitumor activity of HHT is demonstrated in RPMI8226 myeloma xenograft model. Importantly, an additive effect of antitumor is confirmed in the myeloma cells treated with HHT and bortezomib concomitantly with inhibition of phosphorylated Akt. Together, these findings obtained with HHT should give useful insights into a novel antimyeloma chemotherapy. [ABSTRACT FROM AUTHOR]

Clustering is one of the major exploratory techniques for gene expression data analysis. Only with suitable similarity metrics and when datasets are properly preprocessed, can results of high quality be obtained in cluster analysis. In this study, gene expression datasets with external evaluation criteria were preprocessed as normalization by line, normalization by column or logarithm transformation by base-2, and were subsequently clustered by hierarchical clustering, k-means clustering and self-organizing maps (SOMs) with Pearson correlation coefficient or Euclidean distance as similarity metric. Finally, the quality of clusters was evaluated by adjusted Rand index. The results illustrate that k-means clustering and SOMs have distinct advantages over hierarchical clustering in gene clustering, and SOMs are a bit better than k-means when randomly initialized. It also shows that hierarchical clustering prefers Pearson correlation coefficient as similarity metric and dataset normalized by line. Meanwhile, k-means clustering and SOMs can produce better clusters with Euclidean distance and logarithm transformed datasets. These results will afford valuable reference to the implementation of gene expression cluster analysis. [ABSTRACT FROM AUTHOR]

Presents a study which investigated the role of isoform of dynamin, dynamin 2, on adipocyte GLUT-4 internalization, and determined whether dynamin splice variants have functional specificity. Methodology; Results of the study; Discussion.

• This article first discovered that CAR can inhibit the growth of osteosarcoma. • In this article, while studying the effect of CAR on osteosarcoma, it also studies its toxic and side effects on normal cells. • This article also studies the role of CAR in vitro and in vivo. • This study confirmed the mechanism of CAR inhibiting osteosarcoma through P 38 and JNK signaling pathway inhibitors. Osteosarcoma (OS) is the most common type of bone malignant tumors. Clinical commonly used therapeutic drugs of OS treatment are prone to toxic and side effects, so it is very urgent to develop new drugs with low toxicity and low side effects. As a Chinese herbal medicine, Cardamonin (CAR) (C 16 H 14 O 4) has inhibitory effects in various tumors. In the present study, we investigated the effects of CAR on OS cells in vitro and in vivo. We found that CAR inhibited cell proliferation, reduced migration, decreased invasion, and induced G2 / M arrest of OS cells. Notably, we demonstrated that CAR had no obvious effect on proliferation and apoptosis of normal cells. Besides, CAR repressed tumor growth of OS cells in xenograft mouse model. Mechanically, we found that CAR increased the phosphorylation level of P38 and JNK. In summary, our research validates that CAR may inhibit the proliferation, migration, and invasion of OS and promote apoptosis possibly by activating P38 and JNK Mitogen-activated protein kinase (MAPK) signaling pathway. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on the utility of homoarringtonine in treating refractory multiple myeloma.

Ulcerative colitis (UC) is regarded as a recurring inflammatory disorder of the gastrointestinal tract, for which treatment approaches remain notably limited. In this study, we demonstrated that ginseng polysaccharides (GPs) could alleviate the development of dextran sulfate sodium (DSS)-induced UC as reflected by the ameliorated pathological lesions in the colon. GPs strikingly suppressed the expression levels of multiple inflammatory cytokines, as well as significantly inhibited the infiltration of inflammatory cells. Microbiota-dependent investigations by virtue of 16S rRNA gene sequencing, antibiotic treatment and fecal microbiota transplantation illustrated that GPs treatment prominently restored intestinal microbial balance predominantly through modulating the relative abundance of Lactobacillus. Additionally, GPs remarkably influenced the levels of microbial tryptophan metabolites, diminished the intestinal permeability and strengthened intestinal barrier integrity via inhibiting the 5-HT/HTR3A signaling pathway. Taken together, the promising therapeutic potential of GPs on the development of UC predominantly hinges on the capacity to suppress the expression of inflammatory cytokines as well as to influence Lactobacillus and microbial tryptophan metabolites. [Display omitted] [ABSTRACT FROM AUTHOR]

• An automatic fundamental contour extraction of dugong chirps was presented. • Five categories of dugong chirps were identified. • A specific classification criterion was proposed for the automatic and effective identification of chirp types. • Our results enrich the known repertoire of dugong chirps, and may be useful in future passive acoustic monitoring studies. A steady decrease in the Dugong (Dugong dugon) population has been notices worldwide. Considering the social function and utilization rate, dugong chirp classification has become an important bioacoustics research topic, which may help marine biologists monitor the change of their population, study their behavioral context in different environments and optimise the protection policy. However, the objective classification of dugong chirps has not been adequately addressed in the literature. In this paper, an automatic fundamental contour extraction using the tempo-frequency variables to describe the contours of the fundamental frequency of the chirps is presented. With the automatic fundamental contour extraction, the time–frequency information of dugong chirps can be effectively represented, which gives a good classification performance. Following the principles used for the classification of dolphin whistles, three variables were chosen and performed with hierarchical cluster analysis. Based on these results and further visual examination, five categories of chirps were identified. A simple classification criterion was proposed which could be used in the automatic and effective identification of chirp types. Our findings enrich the known repertoire of dugong chirps, and may be useful in future passive acoustic monitoring studies. [ABSTRACT FROM AUTHOR]

Background: Stem cell transplantation shows great potential to improve the long-term survival of cirrhosis patients. However, therapeutic effects may not be homogeneous across the whole study population. This study constructed an easy-to-use nomogram to improve prognostic prediction and aid in treatment decision making for cirrhotic patients. Methods: From August 2005 to April 2019, 315 patients with decompensated cirrhosis receiving autologous peripheral blood stem cell (PBSC) transplantation were enrolled in this study. They were randomly classified into training (2/3) and validation (1/3) groups. A predictive model was developed using Cox proportional hazard models and subsequently validated. The predictive performance of the model was evaluated and also compared with other prognostic models. Results: Age, creatinine, neutrophil-to-lymphocyte ratio, and Child–Turcotte–Pugh class were included in the nomogram as prognostic variables. The nomogram showed high discrimination power concerning the area under receiver operating characteristic curves (3/5-year AUC: 0.742/0.698) and good consistency suggested by calibration plots. Patients could be accurately stratified into poor- and good-outcome groups regarding liver-transplantation free survival after receiving PBSC therapy (P < 0.001). Compared with poor-outcome group, the liver function of patients listed for liver transplantation in the good-outcome group was significantly improved (P < 0.001). Besides, our nomogram achieved a higher C-index (0.685, 95% CI 0.633–0.738) and better clinical utility compared with other conventional prognostic models. Conclusions: The proposed nomogram facilitated an accurate prognostic prediction for patients with decompensated cirrhosis receiving PBSC transplantation. Moreover, it also held the promise to stratify patients in clinical trials or practice to implement optimal treatment regimens for individuals. [ABSTRACT FROM AUTHOR]

Summary: To reducing chemotherapy‐related toxicity, the chemo‐free regimens become a new trend of Ph + ALL treatment. Therefore, we conducted a phase 2 trial of dasatinib plus prednisone, as induction (Course I) and early consolidation (Courses II and III) treating newly diagnosed Ph + ALL. The trial was registered at www.chictr.org.cn, ChiCTR2000038053. Forty‐one patients were enrolled from 15 hospitals. The complete remission (CR) was 95% (39/41), including two elderly induction deaths. By the end of Course III, 25.6% (10/39) of patients achieved a complete molecular response. With a median follow‐up of 15.4 months, 2‐year disease‐free survival (DFS) were 100% and 33% for patients who receiving haematopoietic stem cell transplantation (HSCT) at CR1 and receiving chemotherapy alone respectively. When censored at time of HSCT, 2‐year DFS were 51% and 45% for young and elderly patients (p = 0.987). 2‐year overall survival were 45%, 86% and 100% for patients without HSCT, receiving HSCT after relapse and receiving HSCT at CR1 respectively. A total of 12 patients had marrow recurrences and one had CNS relapse, with 38% occurred early (between Courses I and III). IKZF1 gene deletion was shown to be associated with relapse (p = 0.019). This chemo‐free induction and early consolidation regimen was efficacious and well‐tolerated in de novo Ph + ALL. Allogeneic HSCT conferred definite survival advantage after chemo‐free induction. [ABSTRACT FROM AUTHOR]

B-cell lymphoma is the most prevalent type of non-Hodgkin lymphoma, for which the standard treatment regimen includes rituximab combined with CHOP. However, some patients may develop interstitial pneumonitis (IP), which can be caused by various factors; one of the most important factors is Pneumocystis jirovecii. It is crucial to investigate the pathophysiology of IP and implement preventive measures since IP can be fatal for some people. The data were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, where patients with B-cell lymphoma received the R-CHOP/R-CDOP regimen with or without prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX). Multivariable logistic regression and propensity score matching (PSM) were used to investigate any potential association. Eight hundred thirty-one patients with B-cell lymphoma were classified into two groups: the non-prophylaxis group without TMP-SMX (n=699) and the prophylaxis group with TMP-SMX (n = 132). IP occurred in 66 patients (9.4%, all in the non-prophylaxis group), with an onset median of three cycles of chemotherapy. Multiple logistic regression analysis demonstrated that IP incidence was associated with pegylated liposome doxorubicin (OR=3.29, 95% CI 1.84–5.90, P<0.001). After utilizing a 1:1 matching algorithm for PSM, 90 patients from each group were obtained. There was a statistical difference between the two cohorts in the IP incidence (non-prophylaxis 12.2% vs prophylaxis 0.0%, P <0.001). The prophylactic use of TMP-SMX could prevent the occurrence of IP whose risk factor was pegylated liposome doxorubicin after chemotherapy for B-cell lymphoma. [ABSTRACT FROM AUTHOR]

[Display omitted] • The novel Ginkgo biloba extract (nGBE) improved long-term neurofunction after cerebral ischemia. • nGBE reduced microglia-related inflammation. • nGBE promoted white matter integrity. Ginkgo biloba L. leaf extract (GBE) has been added in many commercial herbal formulations such as EGb 761 and Shuxuening Injection to treat cardiovascular diseases and stroke worldwide. However, the comprehensive effects of GBE on cerebral ischemia remained unclear. Using a novel GBE (nGBE), which consists of all the compounds of traditional (t)GBE and one new compound, pinitol, we investigated its effect on inflammation, white matter integrity, and long-term neurological function in an experimental stroke model. Both transient middle cerebral artery occlusion (MCAO) and distal MCAO were conducted in male C57/BL6 mice. We found that nGBE significantly reduced infarct volume at 1, 3, and 14 days after ischemia. Sensorimotor and cognitive functions were superior in nGBE treated mice after MCAO. nGBE inhibited the release of IL-1β in the brain, promoted microglial ramification, and regulated the microglial M1 to M2 phenotype shift at 7 days post injury. In vitro analyses showed that nGBE treatment reduced the production of IL-1β and TNFα in primary microglia. Administration of nGBE also decreased the SMI-32/MBP ratio and enhanced myelin integrity, thus exhibiting improved white matter integrity at 28 days post stroke. These findings demonstrate that nGBE protects against cerebral ischemia by inhibiting microglia-related inflammation and promoting white matter repair, suggesting that nGBE is a promising therapeutic strategy for long-term recovery after stroke. [ABSTRACT FROM AUTHOR]

Milling processing is an important way to obtain wood-polyethylene composite (WPC) end products. In order to improve the processing efficiency and surface quality of WPC and meet the practical application requirements, this paper focussed on morphology and roughness of the WPC-milled surface and studied surface quality changes under different cutting parameters and milling methods through multi-parameters milling experiments. The milling surface morphology and roughness of WPC were analyzed and measured during cut-in, cutting and cut-out sections. It also revealed the affect rule of different cutting parameters and milling methods on milled surface morphology and roughness. The results show that the milling surface roughness of WPC products with wood powder content of 70% is significantly larger than the one whose wood powder content is 60%, and defects such as holes are also relatively more. Finally, a surface roughness prediction model was established based on the mathematical regression method and its multi-factor simulation was carried out. A comparative analysis of predictive and experimental values was performed to verify the reliability of the model. It could also provide theoretical guidance and technical guarantee for high processing quality of WPC milling and cutting. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteosarcoma (OS) is a primary malignant tumor of bone. Macropinocytosis, a form of non-selective nutrient endocytosis, has received increasing attention as a novel target for cancer therapy, yet its role in OS cells remains obscure. Benzethonium chloride (BZN) is an FDA-approved antiseptic and bactericide with broad-spectrum anticancer effects. Here, we described that BZN suppressed the proliferation, migration, and invasion of OS cells in vitro and in vivo. Mechanistically, BZN repressed the ERK1/2 signaling pathway, and the ERK1/2 activator partially neutralized the inhibitory effect of BZN on OS cells. Subsequently, we demonstrated that OS cells might employ macropinocytosis as a compensatory survival mechanism in response to BZN. Remarkably, macropinocytosis inhibitors enhanced the anti-OS effect of BZN in vitro and in vivo. In conclusion, our results suggest that BZN may inhibit OS cells by repressing the ERK1/2 signaling pathway and propose a potential strategy to enhance the BZN-induced inhibitory effect by suppressing macropinocytosis. Osteosarcoma (OS) is a primary malignant tumor of bone. Chemotherapy is one of the crucial approaches to prevent its metastasis and improve prognosis. Despite continuous improvements in the clinical treatment of OS, tumor resistance and metastasis remain dominant clinical challenges. Macropinocytosis, a form of non-selective nutrient endocytosis, has received increasing attention as a novel target for cancer therapy, yet its role in OS cells remains obscure. Benzethonium chloride (BZN) is an FDA-approved antiseptic and bactericide with broad-spectrum anticancer effects. Here, we described that BZN suppressed the proliferation, migration, and invasion of OS cells in vitro and in vivo, but simultaneously promoted the massive accumulation of cytoplasmic vacuoles as well. Mechanistically, BZN repressed the ERK1/2 signaling pathway, and the ERK1/2 activator partially neutralized the inhibitory effect of BZN on OS cells. Subsequently, we demonstrated that vacuoles originated from macropinocytosis and indicated that OS cells might employ macropinocytosis as a compensatory survival mechanism in response to BZN. Remarkably, macropinocytosis inhibitors enhanced the anti-OS effect of BZN in vitro and in vivo. In conclusion, our results suggest that BZN may inhibit OS cells by repressing the ERK1/2 signaling pathway and propose a potential strategy to enhance the BZN-induced inhibitory effect by suppressing macropinocytosis. [ABSTRACT FROM AUTHOR]

• The sound propagation problems of classical/generalized line sources are solved. • The proposed algorithm and program are unconditionally stable. • The proposed algorithm is naturally parallel. • The normal mode solver based on the spectral method can accurately simulate seabeds. A high-precision numerical sound field is the basis of underwater target detection, positioning and communication. A line source in a plane is a common type of sound source in computational ocean acoustics. The exciting waveguide in a range-dependent ocean environment is often structurally complicated; however, traditional algorithms often assume that the waveguide has a simple seabed boundary and that the line source is located at a horizontal range of 0 m, although this ideal situation is rarely encountered in the actual ocean. In this paper, a novel algorithm is designed that can solve for the sound field excited by a line source at any position in a range-dependent ocean environment. The proposed algorithm uses the classic stepwise approximation approach to address the range dependence of the environment and uses the Chebyshev–Tau spectral method to solve for the horizontal wavenumbers and modes of approximately range-independent segments. Once the modal information of these flat segments has been obtained, a global matrix is constructed to solve for the coupling coefficients of all segments, and finally, the complete sound field is synthesized. Numerical experiments using a robust numerical program developed based on this algorithm verify the correctness and usability of our novel algorithm and software. Furthermore, a detailed analysis and test of the computational cost of this algorithm show that it is efficient. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is among the most common cancers worldwide. Machine learning–based radiomics model could predict axillary lymph node metastasis (ALNM) of BC accurately. Purpose: The purpose is to develop a machine learning model to predict ALNM of BC by focusing on the radiomics features of axillary lymphatic node (ALN). Methods: A group of 398 BC patients with 800 ALNs were retrospectively collected. A set of patient characteristics were obtained to form clinical factors. Three hundred and twenty‐six radiomics features were extracted from each region of interest for ALN in contrast‐enhanced computed tomography (CECT) image. A framework composed of four feature selection methods and 14 machine learning classification algorithms was systematically applied. A clinical model, a radiomics model, and a combined model were developed using a cross‐validation approach and compared. Metrics of the area under the curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the performance of these models in the prediction of ALNM in BC. Results: Among the 800 cases of ALNs, there were 388 cases of positive metastasis (48.50%) and 412 cases of negative metastasis (51.50%). The baseline clinical model achieved the performance with an AUC = 0.8998 (95% CI [0.8540, 0.9457]). The radiomics model achieved an AUC = 0.9081 (95% CI [0.8640, 0.9523]). The combined model using the clinical factors and radiomics features achieved the best results with an AUC = 0.9305 (95% CI [0.8928, 0.9682]). Conclusions: Combinations of feature selection methods and machine learning‐based classification algorithms can develop promising predictive models to predict ALNM in BC using CECT features. The combined model of clinical factors and radiomics features outperforms both the clinical model and the radiomic model. [ABSTRACT FROM AUTHOR]

A novel recombinant SIRPα-Fc fusion protein, IMM01, was constructed and produced using an in-house developed CHO-K1 cell expression system, and the anti-tumor mechanism of IMM01 targeting the CD47-SIRPα pathway was explored. The phagocytosis and in vitro anti-tumor activity of IMM01 were evaluated by antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) assays. In vivo mouse tumor model studies were used to explore therapeutic efficacy as well as the mechanism of action. An in vitro binding assay revealed that IMM01 has a strong binding affinity to CD47 with an EC50 of 0.4967 nM. IMM01 can induce strong ADCP and moderate ADCC, but not CDC. IMM01-induced strong phagocytosis against tumor cells was attributed to dual activities of blocking the "don't eat me" signal and activating the "eat me" signal, and IMM01 exhibits strong and robust in vivo anti-tumor activities either as monotherapy on hematological malignancies, or in combination therapy with PD-L1 monoclonal antibody (mAb), PD-1 mAb, and HER-2 mAb on solid tumors. Finally, IMM01 demonstrated a favorable safety profile with no human RBC binding activity or hemagglutination induction. IMM01 inhibits the growth of tumor cells by the following three possible mechanisms: (1) directly activating macrophages to phagocytize tumor cells; (2) activated macrophages degrade phagocytized tumor cells and present tumor antigens to T cells through MHC molecules to activate T cells; (3) activated macrophages can convert "cold tumors" into "hot tumors" and increase the infiltration of immune cells through chemotaxis by secreting some cytokines and chemokines. [ABSTRACT FROM AUTHOR]

The article presents a research which examines whether exposure to angiotensin converting enzyme (ACE) inhibitors during the first trimester of pregnancy increase the risk of malformations in live born offspring. It is reported that, the researchers used retrospective cohort method for conducting the research. According to the research, neither the use of ACE inhibitors nor the use of any other antihypertensives in the first trimester results in increased risk of congenital heart defects.

• An advanced detection neural network, the improved Faster R-CNN, is presented to realize the localization and classification of axillary lymph nodes (ALNs) simultaneously, which not only classifies lymph node metastasis, but also provides doctors with the position of ALNs in the image for reference. • As ALN usually appears on the left and right sides of CECT images, an attention model, which has the ability of extracting spatial information, was added into the network, aiming to further improve the performance of the algorithm in positioning ALN. • A novel model constructed by channel fusion and bottle neck architecture is proposed and placed before the flatten operation to better fuse and transmit spatial information with less computational cost. Background and objective: Preoperative imaging diagnosis of axillary lymph node (ALN) metastasis is particularly important for breast cancer patients. This paper focuses on developing non-invasive and automatic schemes for accurate localization and classification (metastasis prediction) of ALN via contrast-enhanced computed tomography (CECT) image and deep learning models. Methods: Based on a two-stage strategy, a novel detection neural network is proposed, where the convolutional block attention module is utilized to extract spacial information and the bottleneck feature fusion module is designed for feature fusion in different scales. Results: Owing to the two embedded modules, the proposed convolutional neural network (CNN) model outperforms Faster R-CNN, YOLOv3, and EfficientDet in the sense that the achieved mAP is 0.454, higher than 0.247, 0.335, and 0.329, respectively. In particular, considering the function of classification only, the proposed model reaches the best performance on most indices (accuracy of 0.968, positive predictive value of 0.972, negative predictive value of 0.966, specificity of 0.983), compared with the methods that have been frequently adopted to predict ALN. In addition, the proposed CNN model has the function of locating ALN, which is lacking in existing models. Conclusions: In this paper, a supervised deep learning method is proposed to detect ALN in CECT images. The positive effect of new added modules are verified, and the benefits of spatial information in ALN detection are confirmed. Further, the two subtasks called localization and classification are evaluated separately, where the proposed model achieves the best performance on most indices. The source code mentioned in this article will be released later. [ABSTRACT FROM AUTHOR]

The effects of laser welding parameters on the interface microstructure of AZ31B magnesium alloy and 304 stainless steel were investigated. After welding, a scanning electron microscope and ultra-depth of field microscope were used to observe the microstructure of the welded material, to analyze the effects of power on the interface morphology. The simulation of laser welding of magnesium and steel was carried out by the COMSOL software. The results showed that when the power was 15 W–20 W, the temperature did not reach the melting point of magnesium alloy, there was MgO at the welding, and the interface had poor connection strength. When the power was 35 W–50 W, the temperature reached or even exceeded the boiling point of magnesium alloy, and the interface formed hot cracks, pores, and oxides and had poor joint strength. When the power was 25 W–30 W, the temperature was between the melting point and boiling point of magnesium, and the interface had excellent connection strength. [ABSTRACT FROM AUTHOR]

The combination of rituximab, lenalidomide, and Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib, followed by chemotherapy, has shown high efficacy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) in Smart Start trial. We aimed to evaluate the efficacy, safety of SMART (rituximab + lenalidomide + BTKi) regimen and SMART–START regimen as a first-line treatment in elderly or unfit DLBCL patients. 31 patients were included, 17 used SMART regimen, with median age 82 years, 14 unfit patients received SMART–START regimen. 14/16 (87.5%) patients in SMART group achieved overall response (OR), with 10/16 (62.5%) achieved complete response (CR). 12/13 (92.3%) patients in SMART–START group achieved OR, with 8/13 (61.5%) achieved CR. With a median follow-up of 15.4 (3–29.1) months, median progression-free survival (PFS) and overall survival (OS) have not been reached, 1-year PFS was 81% in SMART group and 84% in SMART–START group. Common grade 3–4 adverse events (AEs) during SMART regimen were neutropenia (8 [25.8%]), infection (6 [19.4%]) and skin rash (3 [9.7%]). Our study shows that SMART regimen is an effective and safe therapy for elderly DLBCL patients, and SMART–START regimen can be used in unfit patients who could not tolerate intensive chemotherapy in the onset. [ABSTRACT FROM AUTHOR]

Background: Targeting the CD47/SIRPα signaling pathway represents a novel approach to enhance anti-tumor immunity. However, the crystal structure of the CD47/SIRPα has not been fully studied. This study aims to analyze the structure interface of the complex of CD47 and IMM01, a novel recombinant SIRPα-Fc fusion protein. Methods: IMM01-Fab/CD47 complex was crystalized, and diffraction images were collected. The complex structure was determined by molecular replacement using the program PHASER with the CD47-SIRPαv2 structure (PDB code 2JJT) as a search model. The model was manually built using the COOT program and refined using TLS parameters in REFMAC from the CCP4 program suite. Results: Crystallization and structure determination analysis of the interface of IMM01/CD47 structure demonstrated CD47 surface buried by IMM01. Comparison with the literature structure (PDB ID 2JJT) showed that the interactions of IMM01/CD47 structure are the same. All the hydrogen bonds that appear in the literature structure are also present in the IMM01/CD47 structure. These common hydrogen bonds are stable under different crystal packing styles, suggesting that these hydrogen bonds are important for protein binding. In the structure of human CD47 in complex with human SIRPα, except SER66, the amino acids that form hydrogen bonds are all conserved. Furthermore, comparing with the structure of PDB ID 2JJT, the salt bridge interaction from IMM01/CD47 structure are very similar, except the salt bridge bond between LYS53 in IMM01 and GLU106 in CD47, which only occurs between the B and D chains. However, as the side chain conformation of LYS53 in chain A is slightly different, the salt bridge bond is absent between the A and C chains. At this site between chain A and chain C, there are a salt bridge bond between LYS53 (A) and GLU104 (C) and a salt bridge bond between HIS56 (A) and GLU106 (C) instead. According to the sequence alignment results of SIRPα, SIRPβ and SIRPγ in the literature of PDB ID 2JJT, except ASP100, the amino acids that form common salt bridge bonds are all conserved. Conclusion: Our data demonstrated crystal structure of the IMM01/CD47 complex and provides a structural basis for the structural binding interface and future clinical applications. [ABSTRACT FROM AUTHOR]

Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/ -catenin signaling pathways NTZ promotes apoptosis of OS cells Next, we sought to investigate whether OS cells apoptosis was affected by NTZ. NTZ inhibits OS cell growth and metastasis in vivo The above results have indicated that NTZ may inhibit OS cells growth and metastasis I in vitro i . Keywords: apoptosis; metastasis; osteosarcoma; proliferation; signaling pathways EN apoptosis metastasis osteosarcoma proliferation signaling pathways 929 943 15 09/13/22 20220901 NES 220901 Introduction Osteosarcoma (OS) is the most common primary tumor of bone, which predominantly affects adolescents, with a second smaller peak of incidence in elderly individual ([10]). [Extracted from the article]

Background: Mesenchymal stem cell (MSC) therapy has been shown to be a promising option for liver fibrosis treatment. However, critical factors affecting the efficacy of MSC therapy for liver fibrosis remain unknown. Follistatin-like 1 (FSTL1), a TGF-β-induced matricellular protein, is documented as an intrinsic regulator of proliferation and differentiation in MSCs. In the present study, we characterized the potential role of FSTL1 in MSC-based anti-fibrotic therapy and further elucidated the mechanisms underlying its action. Methods: Human umbilical cord-derived MSCs were characterized by flow cytometry. FSTL1low MSCs were achieved by FSTL1 siRNA. Migration capacity was evaluated by wound-healing and transwell assay. A murine liver fibrotic model was created by carbon tetrachloride (CCl4) injection, while control MSCs or FSTL1low MSC were transplanted via intravenous injection 12 weeks post CCl4 injection. Histopathology, liver function, fibrosis degree, and inflammation were analysed thereafter. Inflammatory cell infiltration was evaluated by flow cytometry after hepatic nonparenchymal cell isolation. An MSC-macrophage co-culture system was constructed to further confirm the role of FSTL1 in the immunosuppressive capacity of MSCs. RNA sequencing was used to screen target genes of FSTL1. Results: FSTL1low MSCs had comparable gene expression for surface markers to wildtype but limited differentiation and migration capacity. FSTL1low MSCs failed to alleviate CCl4-induced hepatic fibrosis in a mouse model. Our data indicated that FSTL1 is essential for the immunosuppressive action of MSCs on inflammatory macrophages during liver fibrotic therapy. FSTL1 silencing attenuated this capacity by inhibiting the downstream JAK/STAT1/IDO pathway. Conclusions: Our data suggest that FSTL1 facilitates the immunosuppression of MSCs on macrophages and that guarantee the anti-fibrotic effect of MSCs in liver fibrosis. [ABSTRACT FROM AUTHOR]

Objectives A previous study of ours confirmed that Islet-1 specifically induces differentiation of MSCs into cardiomyocytes, and that one of the mechanisms underlying that process is regulation of histone acetylation. Here, we further explore the mechanism of MSC differentiation into cardiomyocytes from the perspective of interactions between epigenetic modifications. Materials and methods We used lentiviral vectors to overexpress Islet-1 in MSCs, and Ch IP- qPCR, MSP and BSP were performed to detect levels of histone acetylation/methylation and DNA methylation in the GATA4 and Nkx2.5 promoters. To further explore relationships between these epigenetic modifications, we used 5-aza or TSA to interfere with DNA methylation and histone acetylation, respectively, and detected effects on the other two modifications. Results Histone acetylation level increased and its methylation level decreased at GATA4 and Nkx2.5 promoters; DNA methylation level was reduced at the GATA4 promoter but did not change at the Nkx2.5 promoter. Furthermore, 5-aza increased histone acetylation level and reduced its methylation level at the GATA4 promoter but had no effect on the Nkx2.5 promoter; TSA reduced histone methylation and DNA methylation levels at the GATA4 promoter, but it only reduced histone methylation level at the Nkx2.5 promoter. Conclusions Histone acetylation/methylation and DNA methylation were both involved in regulating GATA4 expression, but Nkx2.5 expression was not regulated by DNA methylation. These three modifications had high correlation with each other during regulation of GATA4 and produced a regulation loop at the GATA4 promoter. [ABSTRACT FROM AUTHOR]

Although four species of odontocete and four species of baleen whale have been recorded in Prydz Bay, their vocalizations have been rarely investigated. Underwater vocalizations were recorded during March 2017 in Prydz Bay, Antarctica. Bio-duck sounds, downsweeps, inverted "u" shape signals, whistles, pulsed sounds, and broadband clicks were recorded. Bio-duck sounds and downsweeps were associated with Antarctic minke whales (Balaenoptera bonaerensis) based on visual observations. Similarities between inverted "u" shape signals, biphonic calls, and clicks with vocalizations previously described for killer whales (Orcinus orca) lead us believe the presence of Antarctic killer whales. According to sound structures, signal characteristics, and recording location, Antarctic type C killer whales were the most probable candidates to produce these detected calls. These represent the first detection of inverted "u" shape signals in Antarctic waters, and the first report of Antarctic killer whale in Prydz Bay based on passive acoustic monitoring. The co-existence of Antarctic minke and killer whales may imply that minke whales can detect differences between the sounds of mammal-eating and fish-eating killer whales. Our descriptions of these underwater vocalizations contribute to the limited body of information regarding the distribution and acoustic behavior of cetaceans in Prydz Bay. [ABSTRACT FROM AUTHOR]

To evaluate the prevalence, trends, timing and duration of exposure to antiviral medications during pregnancy within a US cohort of pregnant women and to evaluate the proportion of deliveries with a viral infection diagnosis among women given antiviral medication during pregnancy. Live-born deliveries between 2001 and 2007, to women aged 15-45 years, were included from the Medication Exposure in Pregnancy Risk Evaluation Program, a collaborative research program between the U.S. Food and Drug Administration and eleven health plans. They were evaluated for prevalence, timing, duration, and temporal trends of exposure to antiviral medications during pregnancy. We also calculated the proportion of deliveries with a viral infection diagnosis among those exposed to antiviral medications. Among 664,297 live births, the overall prevalence of antiviral exposure during pregnancy was 4 % (n = 25,155). Between 2001 and 2007, antiviral medication exposure during pregnancy doubled from 2.5 to 5 %. The most commonly used antiviral medication was acyclovir, with 3 % of the deliveries being exposed and most of the exposure occurring after the 1st trimester. Most deliveries exposed to antiviral medications were exposed for less than 30 days (2 % of all live births). Forty percent of the women delivering an infant exposed to antiviral medications had a herpes diagnosis. Our findings highlight the increased prevalence of women delivering an infant exposed to antiviral medications over time. These findings support the need for large, well-designed studies to assess the safety and effectiveness of these medications during pregnancy. [ABSTRACT FROM AUTHOR]

• Successfully joined magnesium and aluminum dissimilar metals by nanosecond pulsed laser welding technology. • The laser power has a significant effect on the weld appearance, interface organization, fracture morphology and mechanical properties. • The heat transfer mechanism of the molten pool is described, and two paths of heat transfer are proposed. • At a laser power of 25 W, the maximum tensile force of the joint is the largest, which is 76.5 N. • The temperature field during the welding process was simulated. AZ31B magnesium alloy and 6061 aluminum alloy of 0.2 mm thickness were joined by nanosecond pulsed laser welding technology, and the effects of nanosecond pulsed laser power on the formation of weld seam, interface microstructure and mechanical properties were investigated, and numerical simulation of the temperature field during the welding process was carried out. The results show that when the laser power is 50 W, more defects such as cracks, pores and sags appeared in the joints due to the high heat input, and these defects resulted in a smaller effective joint area between the metals, which is very unfavorable to the strength of the joints. As the laser power decreases, at a laser power of 25 W, fewer defects are exhibited and the effective joint area becomes larger. As the laser power continues to decrease, the low heat input makes metal melting and joining very difficult. At low laser power, the Mg element intrudes backwards into the aluminum, causing the joint boundary interface to take on a reverse "V" shape. According to the results of the tensile shear experiments, the maximum tensile force of the joint was the highest at a laser power of 25 W, which reached 76.5 N. In addition, it was observed that the effective joint area, the number of oxides and their inclusions, and the degree of angular deformation had a very important effect on the mechanical properties of the joints. The results of temperature field numerical simulation experiments show that the heat is accumulated from outside to inside during the laser scanning process, and whether the temperature in the center of the molten pool reaches the melting point of the alloy can be used as an important basis for analyzing the degree of welding. [ABSTRACT FROM AUTHOR]

The resurrection plant Selaginella pulvinata possesses an extraordinary ability to survive longterm desiccation, with the capacity to recover to normal growth after four years in a desiccated state. To understand the phenomenon, we investigated morphology, cytology, physiology, and performed PacBio single-molecule, real-time (SMRT) sequencing and Illumina RNA-sequencing of S. pulvinata during dehydration and rehydration. The full-length transcriptome dataset of S. puvinata consisted of 78,914 isoforms, and 75,819 isoforms (96.07%) were functionally annotated. The mapping rate of RNA-seq was 86.83–93.46% when utilizing the full-length transcriptome dataset as a reference. A total of 17,934 differentially expressed genes (DEGs) were identified during dehydration and rehydration. During dehydration, swollen chloroplasts and mitochondria, as well as vacuolation occupied space in desiccated cells, which cooperated with dense cytoplasm to inhibit the collapse and folding of desiccated cells. Accumulation and up-regulated gene expressions of osmotic agent and protective proteins contributed to the formation of vacuolation and dense cytoplasm. To reduce ROS damage during dehydration, two strategies were employed in S. pulvinata , i.e., reducing ROS production and scavenging ROS. Reducing exposure area, inactive PSII and down-regulated gene expression in photosynthesis decreased ROS production caused by excessive light absorption. Increased activities and up-regulated gene expressions in antioxidant enzyme system promoted ROS scavenging. ABA signaling pathway was hypothesized to play an important regulatory role in the desiccation tolerance of S. pulvinata due to significant ABA accumulation and up-regulated expressions of related genes during dehydration. Moreover, the comparative transcriptome analysis revealed that the pathways involved in dehydration and rehydration of the resurrection species S. pulvinata , S. lepidophylla and S. sellowii were consistent, indicating the similar desiccation tolerance mechanisms existing in the different resurrection species of Selaginella. Our study preliminarily revealed the desiccation tolerance mechanisms of S. pulvinata , which holds significant potential for inspiring biotechnological strategies aimed at enhancing drought tolerance in crops. • Changes of morphology, physiology, cytology and transcriptome level were observed in S. pulvinata during dehydration and rehydration. • Desiccation tolerance of S. pulvinata was an intricate process orchestrated by many genes and metabolic pathways. • The different resurrection species of Selaginella possessed the similar desiccation tolerance mechanism. [ABSTRACT FROM AUTHOR]