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A novel strategy for segmenting mpox virus images is proposed to address the challenge of distinguishing lesion areas from muscle tissue and other regions of infection. This strategy leverages a multiscale inflated convolutional feature fusion and attentional Swin-Unet approach. In this method, a multi-scale extended convolution module is employed in the coding stage of the Swin-Unet network to enhance complementary features while preserving different features at different scales. Additionally, a triple attention module is integrated into the downsampling process to address the issue of inter-channel independence. Finally, the Swin Transformer Block is utilized to modulate the network segmentation performance by adjusting the iteration count in the encoding and decoding regions. Experimental results on a self-constructed mpox dataset demonstrate that the proposed network achieves a pixel segmentation accuracy of 90.4% and an average intersection-over-union ratio of 80.3%. These values represent improvements of 8.6% and 14.6%, respectively, compared to the original Swin-Unet. This enhancement provides valuable support for the ancillary diagnosis of mpox.

Abstract Backgrounds Allergic airway inflammation is prevalent worldwide and imposes a considerable burden on both society and affected individuals. This study aimed to investigate the therapeutic advantages of mesenchymal stem cells (MSCs) overexpressed interleukin-10 (IL-10) for the treatment of allergic airway inflammation, as both IL-10 and MSCs possess immunosuppressive properties. Methods Induced pluripotent stem cell (iPSC)-derived MSCs were engineered to overexpress IL-10 via lentiviral transfection (designated as IL-10-MSCs). MSCs and IL-10-MSCs were administered intravenously to mice with allergic inflammation induced by ovalbumin (OVA), and the features of allergic inflammation including inflammatory cell infiltration, Th cells in the lungs, and T helper 2 cell (Th2) cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. MSCs and IL-10-MSCs were co-cultured with CD4+ T cells from patients with allergic rhinitis (AR), and the levels of Th2 cells and corresponding type 2 cytokines were studied. RNA-sequence was performed to further investigate the potential effects of MSCs and IL-10-MSCs on CD4+ T cells. Results Stable IL-10-MSCs were established and characterised by high IL-10 expression. IL-10-MSCs significantly reduced inflammatory cell infiltration and epithelial goblet cell numbers in the lung tissues of mice with allergic airway inflammation. Inflammatory cell and cytokine levels in BALF also decreased after the administration of IL-10-MSCs. Moreover, IL-10-MSCs showed a stronger capacity to inhibit the levels of Th2 after co-cultured with CD4+ T cells from patients with AR. Furthermore, we elucidated lower levels of IL-5 and IL-13 in IL-10-MSCs treated CD4+ T cells, and blockade of IL-10 significantly reversed the inhibitory effects of IL-10-MSCs. We also reported the mRNA profiles of CD4+ T cells treated with IL-10-MSCs and MSCs, in which IL-10 played an important role. Conclusion IL-10-MSCs showed positive effects in the treatment of allergic airway inflammation, providing solid support for the use of genetically engineered MSCs as a potential novel therapy for allergic airway inflammation.

IntroductionCotton (Gossypium hirsutum L.) is susceptible to long-term waterlogging stress; however, genomic information of cotton response mechanisms toward long days of waterlogging is quite elusive.MethodsHere, we combined the transcriptome and metabolome expression level changes in cotton roots after 10 and 20 days of waterlogging stress treatment pertaining to potential resistance mechanisms in two cotton genotypes.Results and discussionNumerous adventitious roots and hypertrophic lenticels were induced in CJ1831056 and CJ1831072. Transcriptome analysis revealed 101,599 differentially expressed genes in cotton roots with higher gene expression after 20 days of stress. Reactive oxygen species (ROS) generating genes, antioxidant enzyme genes, and transcription factor genes (AP2, MYB, WRKY, and bZIP) were highly responsive to waterlogging stress among the two genotypes. Metabolomics results showed higher expressions of stress-resistant metabolites sinapyl alcohol, L-glutamic acid, galactaric acid, glucose 1-phosphate, L-valine, L-asparagine, and melibiose in CJ1831056 than CJ1831072. Differentially expressed metabolites (adenosine, galactaric acid, sinapyl alcohol, L-valine, L-asparagine, and melibiose) significantly correlated with the differentially expressed PRX52, PER1, PER64, and BGLU11 transcripts. This investigation reveals genes for targeted genetic engineering to improve waterlogging stress resistance to enhance abiotic stress regulatory mechanisms in cotton at the transcript and metabolic levels of study.

Abstract Background Genetic polymorphisms in the PPARD and NOS1AP is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This study was designed to investigate a potential association of PPARD rs2016520 (T/C) and NOS1AP rs12742393 (A/C) polymorphisms with efficacy of nateglinide in newly diagnosed Chinese patients with type 2 diabetes mellitus (T2DM). Methods Sixty patients with newly diagnosed T2DM were enrolled to identify PPARD rs2016520 and NOS1AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay (PCR–RFLP). All subjects were treated with nateglinide (360 mg/day) for 8 weeks. Anthropometric measurements, clinical laboratory tests were obtained at baseline and after 8 weeks of nateglinide treatment. Results After nateglinide treatment for 8 consecutive weeks, patients with at least one C allele of PPARD rs2016520 showed a smaller decrease in post plasma glucose (PPG), homeostasis model assessment for beta cell function (HOMA-B) than those with the TT genotype did (P

Commercially pure titanium (CP-Ti) has seen major applications in biomedical equipment. The use of selective laser melting (SLM) has become more common concerning the fabrication of CP-Ti components with a complicated shape in biomedical implants, where high strength and ductility are required. However, SLM manufactured CP-Ti often exhibits high strength and low ductility, as well as mechanical anisotropy because SLM process typically results in the formation of long columnar grains comprising of fine acicular α′ martensite. Heat treatment must be preceded to transform the acicular α′ to equiaxed α grain. This study demonstrated that annealing at 650 °C of SLM CP-Ti can create an equiaxed structure, resulting in a weakened texture. The formation of equiaxed grains occurred at two types of microstructural features, acicular α′ and irregular massive (α′m) martensite, which exhibited different sizes, morphologies, and contained different types of substructures under SLM as-fabricated condition. The formation mechanism of equiaxed grains in the α′ region is dominated by the coalescence of acicular α′ of the same variant and the dissolution of α′ into the matrix, whereas the formation mechanism in the α′m region is primarily dominated by the growth of the preexisting subgrains. A small number of equiaxed grains with new orientations were formed in the α′m region. The majority of equiaxed grains were formed in the acicular α′ region and inherited the grain orientations of the preexisting α′ or matrix. Therefore, a similar but weakened texture was inherited from the microstructure of the SLM CP-Ti after annealing.

AIM: To explore the dynamic distribution of pupil size and center, the eccentricity distribution of corneal light reflection, and its correlation analysis about suitable for femtosecond laser combined with excimer laser in situ keratomileusis.METHODS: Randomly selected 225 patients(407 eyes)who underwent femtosecond laser combined with excimer laser in situ keratomileusis at Yanbian University Hospital in 2019 from January to May, preoperative use of Wavelight Allegro Topolyzer Corneal Topography to measure the pupil size and center position, the German Wavelight EX500 excimer Laser(500Hz)records the deviation between the pupil center and the coaxially sighted corneal light reflex when the patient is supine. RESULTS:The average displacement distribution between the center of the cornea and the center of the pupil is 0.322±0.194mm, and 64% of the eyes are ≤0.40mm. The average displacement distribution of P-Dist(the eccentricity between the pupil center and the coaxially sighted corneal light reflex point)is 0.225±0.102mm, and 80% of the eyes are ≤0.30mm. The coaxially sighted corneal light reflex point is mainly deviated to the superior temporal side of the corneal center(34%). The X-axis of the left eye in low light conditions: -0.061±0.084mm, and the X-axis of the right eye: -0.016±0.059mm(P=0.002)(the left eye shifted to the temporal side in the dark light). The corneal transverse diameter(WTW)was positively correlated with changes in pupil diameter(dark pupil diameter-bright pupil diameter)(r=0.270, PCONCLUSION: The left eye should be adjusted to a position of the machining center within 0.061mm. If the cornea is too large, try to maintain a dark light environment during the operation to improve the efficiency of pupil matching. This study further confirms the necessity of rationally positioning the cutting center under different angle kappa states.

Patients with cancer who receive doxorubicin (DOX) treatment can experience cardiac dysfunction, which can finally develop into heart failure. Oxidative stress is considered the most important mechanism for DOX-mediated cardiotoxicity. Rutaecarpine (Rut), a quinazolinocarboline alkaloid extracted from Evodia rutaecarpa was shown to have a protective effect on cardiac disease. The purpose of this study is to investigate the role of Rut in DOX-induced cardiotoxicity and explore the underlying mechanism. Intravenous injection of DOX (5 mg/kg, once a week) in mice for 4 weeks was used to establish the cardiotoxic model. Echocardiography and pathological staining analysis were used to detect the changes in structure and function in the heart. Western blot and real-time PCR analysis were used to detect the molecular changes. In this study, we found that DOX time-dependently decreased cardiac function with few systemic side effects. Rut inhibited DOX-induced cardiac fibrosis, reduction in heart size, and decrease in heart function. DOX-induced reduction in superoxide dismutase (SOD) and glutathione (GSH), enhancement of malondialdehyde (MDA) was inhibited by Rut administration. Meanwhile, Rut inhibited DOX-induced apoptosis in the heart. Importantly, we further found that Rut activated AKT or nuclear factor erythroid 2-related factor 2 (Nrf-2) which further upregulated the antioxidant enzymes such as heme oxygenase-1 (HO-1) and GSH cysteine ligase modulatory subunit (GCLM) expression. AKT inhibitor (AKTi) partially inhibited Nrf-2, HO-1, and GCLM expression and abolished the protective role of Rut in DOX-induced cardiotoxicity. In conclusion, this study identified Rut as a potential therapeutic agent for treating DOX-induced cardiotoxicity by activating AKT.

Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulation of the epigenome has been associated with increased susceptibility to age-related disorders. In this study, we aimed to characterize the age-dependent changes of the epigenome and, in turn, to understand epigenetic processes that drive aging phenotypes. We focused on the aging-associated changes in the repressive histone marks H3K9me3 and H3K27me3 in C. elegans. We observed region-specific gain and loss of both histone marks, but the changes are more evident for H3K9me3. We further found alteration of heterochromatic boundaries in aged somatic tissues. Interestingly, we discovered that the most statistically significant changes reflected H3K9me3-marked regions that are formed during aging, and are absent in developing worms, which we termed "aging-specific repressive regions" (ASRRs). These ASRRs preferentially occur in genic regions that are marked by high levels of H3K9me2 and H3K36me2 in larval stages. Maintenance of high H3K9me2 levels in these regions have been shown to correlate with a longer lifespan. Next, we examined whether the changes in repressive histone marks lead to de-silencing of repetitive DNA elements, as reported for several other organisms. We observed increased expression of active repetitive DNA elements but not global re-activation of silent repeats in old worms, likely due to the distributed nature of repetitive elements in the C. elegans genome. Intriguingly, CELE45, a putative short interspersed nuclear element (SINE), was greatly overexpressed at old age and upon heat stress. SINEs have been suggested to regulate transcription in response to various cellular stresses in mammals. It is likely that CELE45 RNAs also play roles in stress response and aging in C. elegans. Taken together, our study revealed significant and specific age-dependent changes in repressive histone modifications and repetitive elements, providing important insights into aging biology.

Marine-derived fungi are a treasure house for the discovery of structurally novel secondary metabolites with potential pharmaceutical value. In this study, a pair of new nor-bisabolane derivative enantiomers (±)−1 and two new phthalides (4 and 5), as well as four known metabolites, were isolated from the culture filtrate of the marine algal-derived endophytic fungus Penicillium chrysogenum LD-201810. Their structures were established by detailed interpretation of spectroscopic data (1D/2D NMR and ESI-MS). The optical resolution of compound (±)−1 by chiral HPLC successfully afforded individual enantiomers (+)−1 and (−)−1, and their absolute configurations were determined by TDDFT-ECD calculations. Compound (±)−1 represents the first example of bisabolane analogs with a methylsulfinyl substituent group, which is rare in natural products. All of the isolated compounds 1–7 were evaluated for their cytotoxic activity against A549, BT-549, HeLa, HepG2, MCF-7, and THP-1 cell lines, as well as for antifungal activity against four plant pathogenetic fungi (Alternaria solani, Botrytis cinerea, Fusarium oxysporum, and Valsa mali). Compound 2, a bisabolane-type sesquiterpenoid, was shown to possess excellent activity for control of B. cinerea with half-maximal inhibitory concentration (IC50) of 13.6 μg/mL, whereas the remaining investigated compounds showed either weak or no cytotoxic/antifungal activity in this study.

AIM: To investigate the effect of inclination and eccentricity of intraocular lens(IOL),on optical imaging quality via wavefront aberration optical path system.METHODS: The spherical IOL Sensar AR40e, the aspherical monofocal IOL Tecnis ZA9003, and the aspheric multifocal IOL Tecnis ZM900 were measured at the center of the center using a laboratory-built Hartmann-Shack IOL wavefront aberration path system at 5.0mm simulated pupil diameter. 0, 0.2, 0.4, 0.6, 0.8mm, the effect on the optical imaging quality when tilting 5°, 10°, 15°, 20°, 25° to the nasal side and the temporal side, and quantitative imaging quality by high-order aberration and modulation transfer function.RESULTS: The Temnis ZA9003 MTF value was higher than AR40e and Tecnis ZM900 when inclinationed within 5°, while the three IOL MTF values were significantly different when inclinationed 5°, 10°, 15°, and 20°. Tecnis ZA9003 The IOL inclination angle was significantly positively correlated with the coma(r=0.842, Pr=0.229, P=0.241). The three IOL MTF values were obtained when the eccentricity was 0.6 and 0.8 mm. Significant differences(both PCONCLUSION: When the inclination of aspheric IOL(-0.27μm spherical aberration)is less than 5°and the eccentricity is less than 0.4mm, aspherical IOL has a better imaging quality than that of spherical IOL. Tecnis ZM900 IOL has a lower optical imaging quality than that of spherical and aspheric IOL when the eccentricity of IOL is more than 0.4mm.

AIM:To determine the pathological changes in ocular surfaces dry eye excessive evaporation non-obese diabetic(NOD)mice model and to preliminarily explore the feasibility of diabetic dry eye model.METHODS: In this study, 40 females NOD mice were selected. The experimental group consisted of NOD mice that were diagnosed with diabetes while the normal control group consisted of those NOD mice without spontaneous diabetes. Hypodermic injection of Scopolamine hydrobromide(0.5mg/0.2mL)was administered under 40% humidity to the experimental group and placed in a controlled drying box for 12h a day. This was to achieve a dry eye model. Testing indicators on the 1, 7, 10 and 14d after modeling, phenol red thread test was used to measure tear secretion and the eye sections were stained with periodic acid-Schiff(PAS)to examine the morphology and number of conjunctival goblet cells. On the 10d after modeling, the changes in the corneal epithelium were visualized after staining with hematoxylin. RESULTS:For the NOD mice of the experimental group, the tear secretion was gradually decreased with timing, while there were no obvious changes in the normal control group. The volume of the conjunctival goblet cells of the experimental group became larger, and on the 1d after the molding, the experimental group had decreased density of the goblet cells when compared with the normal control group(P=0.008). From the 7d after the molding, as the time was prolonged, the density of the goblet cells was gradually decreased and the differences between the two group at same time point were significant(all PCONCLUSION: Dry eye model of NOD mice was preliminary established, and the changes of ocular surface were similar to those of dry eye in the clinic.

We have performed quantitative analysis of {332}〈113〉 twinning in a β-Ti-15Mo (wt.%) alloy by in situ scanning electron microscopy and electron backscattering diffraction (EBSD). Microstructure-twinning relations were evaluated by statistical analysis of the evolving twin structure upon deformation at room temperature. Our analysis reveals that at the early stages of deformation (ε < 1.5 to 2.0%), primary twinning is mainly determined by the applied macroscopic stress resolved on the twin system. Most of the primary twins (~70–80% of the analyzed twins) follow Schmid’s law with respect to the macroscopic stress, and most of the growth twins (~ 85% of the analyzed twins) correspond to the higher stressed variant. In the grain size range studied here (40–120 μm), we find that several twin parameters such as number of twins per grain and number of twins per grain boundary area exhibit grain size dependence. We ascribe these effects to the grain size dependence of twin nucleation stress and apparent critical resolved shear stress for twinning, respectively.

Abstract Background It has been demonstrated previously that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSCs) have immunosuppressive effects on activated T cells. However, the effects of iPSC-MSCs on quiescent T cells are still unknown. The aim of this study was to identify the immunomodulatory role of iPSC-MSCs on resting peripheral blood mononuclear cells (PBMCs) from allergic rhinitis (AR) patients. Methods PBMCs were cocultured with iPSC-MSCs without any stimulation, following which lymphocyte proliferation, activation of T cells, TH1/TH2 and regulatory T (Treg) cell differentiation, and Treg cell function were analyzed. The roles of soluble factors and cell–cell contact were examined to investigate the mechanisms involved. Results iPSC-MSCs promoted the proliferation of resting lymphocytes, activated CD4+ and CD8+ T cells, and upregulated and activated Treg cells without any additional stimulation. In addition, iPSC-MSCs balanced biased TH1/TH2 cytokine levels. Cell–cell contact was confirmed to be a possible mechanism involved. NF-κB was identified to play an important role in the immunomodulatory effects of iPSC-MSCs on quiescent T cells. Conclusions iPSC-MSCs activate quiescent T cells and elevate regulatory T-cell response in AR patients, suggesting different immunomodulatory functions of iPSC-MSCs according to the phases of diseases. Therefore, iPSC-MSCs are a potential therapeutic candidate for treating allergic airway inflammation.

Abstract Background Human induced pluripotent stem cells-derived mesenchymal stem cells (iPSC-MSCs) have been shown to be effective in Type 2 helper T cells (Th2)-dominant eosinophilic allergic airway inflammation. However, the role of iPSC-MSCs in Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation remains poorly studied. Therefore, this study was to explore the effects of iPSC-MSCs on an experimental mouse model of steroid-resistant neutrophilic airway inflammation and further determine the underlying mechanisms. Methods A mouse model of neutrophilic airway inflammation was established using ovalbumin (OVA) and lipopolysaccharide (LPS). Human iPSC-MSCs were systemically administered, and the lungs or bronchoalveolar lavage fluids (BALF) were collected at 4 h and 48 h post-challenge. The pathology and inflammatory cell infiltration, the T helper cells, T helper cells-associated cytokines, nuclear transcription factors and possible signaling pathways were evaluated. Human CD4+ T cells were polarized to T helper cells and the effects of iPSC-MSCs on the differentiation of T helper cells were determined. Results We successfully induced the mouse model of Th17 dominant neutrophilic airway inflammation. Human iPSC-MSCs but not dexamethasone significantly prevented the neutrophilic airway inflammation and decreased the levels of Th17 cells, IL-17A and p-STAT3. The mRNA levels of Gata3 and RORγt were also decreased with the treatment of iPSC-MSCs. We further confirmed the suppressive effects of iPSC-MSCs on the differentiation of human T helper cells. Conclusions iPSC-MSCs showed therapeutic potentials in neutrophilic airway inflammation through the regulation on Th17 cells, suggesting that the iPSC-MSCs could be applied in the therapy for the asthma patients with steroid-resistant neutrophilic airway inflammation.

Pigment epithelium-derived factor (PEDF) is an oncogene found in various types of cancers. However, how PEDF affects the development of human esophageal squamous cell carcinoma (ESCC) is unknown. This study investigates the role of PEDF in ESCC cell proliferation, migration, and cell cycle both in vitro and in vivo. The PEDF expression was examined in patient tumor samples and ESCC cell lines. Short hairpin RNA technology was used to inhibit the PEDF expression in ESCC EC9706 and KYSE150 cells. In vitro cell proliferation and migration assays were performed. The effects of PEDF on tumor growth and progression were examined in vivo in murine subcutaneous xenograft tumor models. It was found that PEDF was overexpressed in esophageal cancer cells and patient tumor tissues compared to normal control samples. PEDF enhanced cell cycle progression and inhibited cell apoptosis. Knock down of PEDF inhibited esophageal cell proliferation and migration in vitro. Moreover, Inhibition of PEDF significantly reduced tumor growth and tumor size in vivo. These results indicate that PEDF induce tumorigenesis in ESCC and can be a potential therapeutic target for cancer treatment.

Worms with increased levels of the epigenetic mark H3K9me2 have a longer lifespan that can be passed down to future generations.

Purpose. To analyze the distribution of the offset between the pupil center and the coaxially sighted corneal light reflex (P-Dist), the effects of 50% and 100% angle kappa adjustments on refractive and visual quality in patients with moderate myopia were investigated. Methods. A randomly selected 254 patients (254 eyes) with moderate myopia who underwent femtosecond laser-combined LASIK were examined. During the operation, the P-Dist of the patients was recorded by the x- and y-axis eyeball-tracking adjustment program of the WaveLight Eagle Vision EX500 excimer laser system. Preoperatively and 3 months postoperatively, the WaveLight® ALLEGRO Topolyzer was used to measure the pupil size and center position, and the wavefront sensor was used to measure the wavefront aberrations. The visual function tester (OPTEC 6500) measured contrast sensitivity. Results. The average P-Dist was 0.220 ± 0.102 mm. When the P-Dist >0.220 mm, the postoperative residual cylinder was 0.29 ± 0.34 D in the group with the 50% adjustment and 0.40 ± 0.32 D in the 100% group, which was significantly higher than the 50% group P=0.036. The coma was 0.21 ± 0.17 μm in the 50% adjusted group and 0.34 ± 0.25 μm in the 100% group, which was significantly higher than that in the 50% group P=0.021. At the 1.5 c/d spatial frequency, contrast sensitivity in the adjusted 100% group was significantly lower than that in the 50% group under visual glare conditions P=0.039. Conclusion. The postoperative visual acuity and spherical equivalent were not affected in the two groups. However, when P-Dist >0.220 mm, the residual astigmatism and coma were lower in the 50% group. Individualized operations for those with moderate myopia and large-angle kappa in which 100% adjustment is chosen may not result in a better visual quality effect than 50%.

Airway epithelial cell injury is a key triggering event to activate allergic airway inflammation, such as asthma. We previously reported that administration of mesenchymal stem cells (MSCs) significantly alleviated allergic inflammation in a mouse model of asthma, and the mmu-miR-21/ACVR2A axis may be involved. However, whether MSCs protect against bronchial epithelial cell injury induced by hypoxia, and the underlying mechanism, remain unknown. In our study, the human bronchial epithelial cell line BEAS-2B was induced to undergo apoptosis with a hypoxia mimic of cobalt chloride (CoCl 2 ) damage. Treatment of MSCs derived from induced pluripotent stem cells (iPSCs) significantly decreased apoptosis of BEAS-2B cells. There was high miR-21 expression in injured BEAS-2B cells after MSC treatment. Transfection of the miR-21 mimic significantly decreased apoptosis of BEAS-2B, and transfection of a miR-21 inhibitor significantly increased apoptosis. More importantly, the protective effects of MSCs on injured BEAS-2B were reversed by transfection of the miR-21 inhibitor. Binding sites of human miR-21 were identified in the 3’UTR of human ACVR2A. We further determined that CoCl 2 stimulation increased ACVR2A expression at both the mRNA and protein levels. Moreover, transfection of the miR-21 mimic further up-regulated ACVR2A expression induced by CoCl 2 , whereas transfection of the miR-21 inhibitor down-regulated ACVR2A expression. In addition, MSCs increased ACVR2A expression in BEAS-2B cells; however, this effect was reversed after transfection of the miR-21 inhibitor. Our data suggested that MSCs protect bronchial epithelial cells from hypoxic injury via miR-21, which may represent an important target. These findings suggest the potentially wide application of MSCs for epithelial cell injury during hypoxia.

We have investigated the propagation of {332} twins in a multilayered Ti-10Mo-xFe (x = 1–3) alloy fabricated by multi-pass hot rolling. The material contains a macroscopic Fe-graded structure (about 130 μm width) between 1 and 3 wt% Fe in the direction perpendicular to rolling. We observe strong influence of the Fe-graded structure in the twin propagation behavior. The propagation of {332} twins that are nucleated in Fe-lean regions (~1 wt% Fe) is interrupted in the grain interiors at a specific Fe content, namely, about 2 wt% Fe. We ascribe this effect to the role of Fe content in solid solution on the stress for twin propagation. The interruption of twins in the grain interiors results in the development of characteristic dislocation configurations such as highly dense dislocation walls (HDDWs) associated to strain localization phenomena. The nucleation and propagation of these dislocation configurations is ascribed to the underlying plastic accommodation mechanisms of the stress field at the twin tips. We find that the crystallographic alignment of HDDWs is determined by the stress field at the twin tips and the deformation texture. The excellent plastic accommodation at the interrupted twin tips allows attaining the good ductility of the present material (total elongation of 28%).

Near alpha titanium alloys have been widely used in the aerospace industry owing to their high special strength, low-density and excellent corrosion resistance. Ti–3Al–2.5V is a typical near alpha titanium alloy that was usually used in the form of a tube in aircraft due to its excellent cold workability. In the present study, the microstructural evolution and detwinning behavior of cold-rolled Ti–3Al–2.5V alloy tubes during annealing were investigated. Upon annealing, the microstructure evolution strongly depends on the annealing temperature and holding time, which play important roles in the kinetics of the static recovery and recrystallization. In addition, there are two independent detwinning mechanisms involved during annealing. The first one is that detwinning occurs along the twin shear direction at grain boundaries, resulting in a shortening effect. The second one is that detwinning occurs in the center of twins, resulting in a thinning effect of twins. The understanding of the detwinning behavior and microstructural evolution during annealing helps with the tube processing and their applications in aircraft.

Introduction: Cotton (Gossypium hirsutum L.) is susceptible to long-term waterlogging stress; however, genomic information of cotton response mechanisms toward long days of waterlogging is quite elusive. Methods: Here, we combined the transcriptome and metabolome expression level changes in cotton roots after 10 and 20 days of waterlogging stress treatment pertaining to potential resistance mechanisms in two cotton genotypes. Results and discussion: Numerous adventitious roots and hypertrophic lenticels were induced in CJ1831056 and CJ1831072. Transcriptome analysis revealed 101,599 differentially expressed genes in cotton roots with higher gene expression after 20 days of stress. Reactive oxygen species (ROS) generating genes, antioxidant enzyme genes, and transcription factor genes (AP2, MYB, WRKY, and bZIP) were highly responsive to waterlogging stress among the two genotypes. Metabolomics results showed higher expressions of stress-resistant metabolites sinapyl alcohol, L-glutamic acid, galactaric acid, glucose 1-phosphate, L-valine, L-asparagine, and melibiose in CJ1831056 than CJ1831072. Differentially expressed metabolites (adenosine, galactaric acid, sinapyl alcohol, L-valine, L-asparagine, and melibiose) significantly correlated with the differentially expressed PRX52, PER1, PER64, and BGLU11 transcripts. This investigation reveals genes for targeted genetic engineering to improve waterlogging stress resistance to enhance abiotic stress regulatory mechanisms in cotton at the transcript and metabolic levels of study. [ABSTRACT FROM AUTHOR]

Abstract Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity, safeguarding receptor activation, and facilitating amplification of signal transduction across the cellular membrane. However, cell-surface antigen-induced multimerization (dubbed AIM herein) has not yet been consciously leveraged in chimeric antigen receptor (CAR) engineering for enriching T cell-based therapies. We co-developed ciltacabtagene autoleucel (cilta-cel), whose CAR incorporates two B-cell maturation antigen (BCMA)-targeted nanobodies in tandem, for treating multiple myeloma. Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity. Crystallographic analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution. BCMA-induced nanobody CAR multimerization enhanced cytotoxicity, alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release, towards myeloma-derived cells. Our results provide a framework for contemplating the AIM approach in designing next-generation CARs.

Abstract Lateral interaction in the biological brain is a key mechanism that underlies higher cognitive functions. Linear self‐organising map (SOM) introduces lateral interaction in a general form in which signals of any modality can be used. Some approaches directly incorporate SOM learning rules into neural networks, but incur complex operations and poor extendibility. The efficient way to implement lateral interaction in deep neural networks is not well established. The use of Laplacian Matrix‐based Smoothing (LS) regularisation is proposed for implementing lateral interaction in a concise form. The authors’ derivation and experiments show that lateral interaction implemented by SOM model is a special case of LS‐regulated k‐means, and they both show the topology‐preserving capability. The authors also verify that LS‐regularisation can be used in conjunction with the end‐to‐end training paradigm in deep auto‐encoders. Additionally, the benefits of LS‐regularisation in relaxing the requirement of parameter initialisation in various models and improving the classification performance of prototype classifiers are evaluated. Furthermore, the topologically ordered structure introduced by LS‐regularisation in feature extractor can improve the generalisation performance on classification tasks. Overall, LS‐regularisation is an effective and efficient way to implement lateral interaction and can be easily extended to different models.

In the 1980s, Shandong Province took the lead in establishing breakthrough industrialized seedling raising and breeding technologies for Apostichopus japonicus and successfully led the 'fifth wave of mariculture' in China. In 2008, the experiment of 'raising sea cucumber from north to south' proved successful, and sea cucumber culture gradually radiated and extended to Fujian, Jiangsu, Guangdong, and Zhejiang Provinces in southern China. The total output of sea cucumber culture in Shandong Province accounts for more than 70% of the market in China, and the sea cucumber industry is now a pillar of the fishery economy in Shandong Province. This paper systematically introduces the development status of the sea cucumber breeding industry in Shandong Province in recent ten years, summarizes the current problems and challenges, and puts forwards development suggestions; this guidance has significance for the healthy and sustainable development of the sea cucumber breeding industry in both Shandong Province and the whole country. [ABSTRACT FROM AUTHOR]

Average-rendezvous problem with connectivity preservation of constant reference signals is investigated for first-order multiagent systems. According to a constructive potential function, a proportional–integral average-rendezvous algorithm is proposed to make agents converge to the average value of constant reference signals as well as the network connectivity is preserved all the time. Sufficient convergence conditions are obtained for the algorithm by designing the proper Lyapunov functions. Numerical examples illustrate the correctness of theoretical results.

We report the physical properties of the 18 brightest ( S _870 _μ _m = 12.4–19.2 mJy) and not strongly lensed 870 μ m–selected dusty star-forming galaxies (DSFGs), also known as submillimeter galaxies (SMGs), in the COSMOS field. This sample is part of an ALMA band 3 spectroscopic survey (AS2COSPEC), and spectroscopic redshifts are measured in 17 of them at z = 2–5. We perform spectral energy distribution analyses and deduce a median total infrared luminosity of L _IR = (1.3 ± 0.1) × 10 ^13 L _⊙ , infrared-based star formation rate (SFR) of SFR _IR = 1390 ± 150 M _⊙ yr ^−1 , stellar mass of M _* = (1.4 ± 0.6) × 10 ^11 M _⊙ , dust mass of M _dust = (3.7 ± 0.5) × 10 ^9 M _⊙ , and molecular gas mass of M _gas = ( α _CO /0.8)(1.2 ± 0.1) × 10 ^11 M _⊙ , suggesting that they are one of the most massive, ISM-enriched, and actively star-forming systems at z = 2–5. In addition, compared to less massive and less active galaxies at similar epochs, SMGs have comparable gas fractions; however, they have a much shorter depletion time, possibly caused by more active dynamical interactions. We determine a median dust emissivity index of β = 2.1 ± 0.1 for our sample, and by combining our results with those from other DSFG samples, we find no correlation of β with redshift or infrared luminosity, indicating similar dust grain compositions across cosmic time for infrared luminous galaxies. We also find that AS2COSPEC SMGs have one of the highest dust-to-stellar mass ratios, with a median of 0.02 ± 0.01, significantly higher than model predictions, possibly due to too-strong active galactic nucleus feedback implemented in the model. Finally, our complete and uniform survey enables us to put constraints on the most massive end of the dust and molecular gas mass functions.

Conductivity of molten alkali metal chlorides is the foundation of molten-salt electrolysis process. In the study, equilibrium molecular dynamics was performed to investigate the ionic conductivities of the molten alkali metal chloride binary systems. The calculated values were in good agreement with the experimental results. Simple databases for conductivity have been built based on the verified algorithm. Mathematic expressions of conductivity vs. temperature & composition have also been obtained according to calculated data. Ionic conductivities of these melts exhibited positive dependences on temperature. Adding a smaller alkali metal cation into molten alkali chlorides could improve the conductive performance. With the gradual addition of LiCl, ionic conductivities of molten LiCl-NaCl, LiCl-KCl, LiCl-RbCl, and LiCl-CsCl all increased monotonously. The conductivities of molten NaCl-KCl, NaCl-RbCl, and NaCl-CsCl also increased with the continuous addition of NaCl. The improvement effects of LiCl on ionic conductivities of molten KCl, RbCl, and CsCl are more significant than those of NaCl.

DNA methylation and demethylation play a critical role in the regulation of the molecular pathogenesis of gliomas. Tet methylcytosine dioxygenase 1 (TET1) catalyses the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine, (5hmC) leading to eventual DNA demethylation. It has been reported that TET1 is a tumour suppressor in several cancers. However, whether TET1 plays a role in glioma development is largely unclear. Different glioma specimens and corresponding normal controls were collected to analyse the expression of TET1. At the same time, TET1 of glioma U251 cells was knocked down or overexpressed to observe its effect on glioma cell proliferation and invasion as well as autophagy level. Here, we reported that the expression of TET1 in glioma tissue was significantly lower than the corresponding non-tumour normal tissues, and the concentration of TET1 is negatively correlated with the glioma WHO classification. When TET1 gene in glioma U251 cells was knocked down by CRISPR/Caspase-9 system, the proliferation and invasive ability of U251 increased remarkably. But when TET1 was overexpressed in U251 cells, the proliferation and invasion were impaired. Following the down-expression of TET1, the level of autophagy in U251 cells decreased accordingly. However, when TET1 was overexpressed in U251 cells, the level of autophagy incraesed. Furthermore, bafilomycin A1 (Baf-A1) but not 3-methyladenine (3-MA) could decrease the autophagy level of TET1-/- U251 cells as the wild-type controls. It suggests that the tumour suppressor effect of TET1 seems to be mediated by regulating the level of autophagy, and the regulation of TET1 on autophagy is at an early stage. [ABSTRACT FROM AUTHOR]

Fibronectin (FN) is a primary component of the mammary mesenchymal compartment and undergoes dramatic changes during breast cancer development. Increased FN expression is associated with an invasive and metastatic breast cancer phenotype. The present study demonstrated that FN causes an epithelial-mesenchymal transition (EMT)-like morphological change in MCF-7 breast cancer cells. FN stimulation caused the downregulation of epithelial markers E-cadherin and tight junction protein ZO-1, and the upregulation of mesenchymal markers N-cadherin and vimentin. Additionally, FN promoted cell migration and invasion in MCF-7 cells, with increased expression of calpain-2 and proteolysis of focal adhesion kinase 1 (FAK), indicating calpain activation. Notably, the FN induced changes in morphology and EMT markers were reversed with the treatment of calpain-specific inhibitors, calpain inhibitor I (N-acetyl-L-leucyl-L-leucyl-L-norleucinal), calpeptin and calpain inhibitor IV. Meanwhile, the effects of FN on cell migration and invasion, as well as FAK proteolysis were markedly suppressed by calpain inhibitors. Taken together, the results of the present study indicate that calpain plays an essential role in FN-induced EMT response, and that targeting calpain signaling may be a potential strategy to reduce breast cancer metastasis. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have potent immunomodulatory effects on multiple immune cells and have great potential in treating immune disorders. Induced pluripotent stem cells (iPSCs) serve as an unlimited and noninvasive source of MSCs, and iPSC-MSCs have been reported to have more advantages and exhibit immunomodulation on T lymphocytes and natural killer cells. However, the effects of iPSC-MSCs on dendritic cells (DCs) are unclear. The aim of this study is to investigate the effects of iPSC-MSCs on the differentiation, maturation, and function of DCs. Methods: Human monocyte-derived DCs were induced and cultured in the presence or absence of iPSC-MSCs. Flow cytometry was used to analyze the phenotype and functions of DCs, and enzyme-linked immunosorbent assay (ELISA) was used to study cytokine production. Results: In this study, we successfully induced MSCs from different clones of human iPSCs. iPSC-MSCs exhibited a higher proliferation rate with less cell senescence than BM-MSCs. iPSC-MSCs inhibited the differentiation of human monocyte-derived DCs by both producing interleukin (IL)-10 and direct cell contact. Furthermore, iPSC-MSCs did not affect immature DCs to become mature DCs, but modulated their functional properties by increasing their phagocytic ability and inhibiting their ability to stimulate proliferation of lymphocytes. More importantly, iPSC-MSCs induced the generation of IL-10-producing regulatory DCs in the process of maturation, which was mostly mediated by a cell-cell contact mechanism. Conclusions: Our results indicate an important role for iPSC-MSCs in the modulation of DC differentiation and function, supporting the clinical application of iPSC-MSCs in DC-mediated immune diseases. [ABSTRACT FROM AUTHOR]

ABSTRACT: In the greater inland Jianghan Basin of South China, three salt depressions are lacking accurate geological times, of which Jiangling Depression is the largest. Evaporites are important records of paleoclimate, however, the geological ages of evaporates are very difficult to be determined because often evaporates have scare macrofossils and microfossils. Nonmarine Cretaceous to Tertiary halite deposits interbedded with mudstones are widely distributed in China. Paleocene-Eocene Thermal Maximum had very high temperatures and attracted strong interests of geologists because these times can be compared with future climate change because of global warming. However, previous studies focused on marine sediments found that during the Paleocene-Early Eocene, massive evaporate deposits formed in Jiangling depression of the Jianghan Basin. In this paper, the authors show that the Shashi Formation halite deposits formed in the Paleocene according to palynology. Most of these palynology fossils are arid types, so the massive evaporites in the Jiangling depression could be closely related to the hot Paleocene climate. High temperatures during the Paleocene contributed to the formation of the massive evaporates in the Jiangling Depression, until sylvite was the result.

We present the initial results of an ongoing survey with the Karl G. Jansky Very Large Array targeting the CO( J = 1–0) transition in a sample of 30 submillimeter-selected, dusty star-forming galaxies (SFGs) at z = 2–5 with existing mid- J CO detections from the Atacama Large Millimeter/submillimeter Array and NOrthern Extended Millimeter Array, of which 17 have been fully observed. We detect CO(1–0) emission in 11 targets, along with three tentative (∼1.5 σ –2 σ ) detections; three galaxies are undetected. Our results yield total molecular gas masses of 6–23 × 10 ^10 ( α _CO /1) M _⊙ , with gas mass fractions, f _gas = M _mol /( M _* + M _mol ), of 0.1–0.8 and a median depletion time of (140 ± 70) Myr. We find median CO excitation ratios of r _31 = 0.75 ± 0.39 and r _41 = 0.63 ± 0.44, with significant scatter. We find no significant correlation between the excitation ratio and a number of key parameters such as redshift, CO(1–0) line width, or Σ _SFR . We only find a tentative positive correlation between r _41 and the star-forming efficiency, but we are limited by our small sample size. Finally, we compare our results to predictions from the SHARK semi-analytical model, finding a good agreement between the molecular gas masses, depletion times, and gas fractions of our sources and their SHARK counterparts. Our results highlight the heterogeneous nature of the most massive SFGs at high redshift, and the importance of CO(1–0) observations to robustly constrain their total molecular gas content and interstellar medium properties.

Background: We have previously reported that induced pluripotent stem cell (iPSC)-mesenchymal stem cells (MSCs) alleviated asthma inflammation in mice. Long noncoding RNAs (lncRNAs) were recently reported as being involved in the immune responses. However, whether lncRNAs are associated with iPSC-MSC immunomodulation in allergic inflammation is still unclear. Methods: Mice were induced into an asthmatic state and received treatment consisting of iPSC-MSCs. Memory T cells isolated from sensitized mice were challenged and co-cultured with iPSC-MSCs in vitro. Total RNA from the lungs and separated T cells were processed with an lncRNA/mRNA microarray. A series of bioinformatics technologies were used to screen the target lncRNAs. Results: iPSC-MSCs significantly prevented asthma inflammation and decreased the Th2 cytokine levels. Over 1300 lncRNAs were differentially expressed after the induction of asthma, and 846 or 4176 lncRNAs were differentially expressed with iPSC-MSC treatment in mice or in vitro, respectively. After overlapping the differentially expressed lncRNAs produced in a similar manner in mice and in vitro, 23 lncRNAs and 96 mRNAs were selected, in which 58 protein-coding genes were predicted to be potential targets of the 23 lncRNAs. Furthermore, using a series of bioinformatics technologies, 9 lncRNAs co-expressed with the most differentially expressed mRNAs, which were enriched in terms of the immune response, were screened out via Pearson's correlation coefficient with mRNAs that were involved with inflammatory cytokines and receptors. lncRNAs MM9LINCRNAEXON12105+ and AK089315 were finally emphasized via quantitative real-time PCR validation. Conclusions: Our results suggested that aberrant lncRNA profiles were present after asthma induction and iPSCMSC treatment, suggesting potential targets of allergic inflammation and iPSC-MSC-mediated immunomodulation. [ABSTRACT FROM AUTHOR]

Administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs) significantly alleviates allergic airway inflammation. There are no studies that refer to the role of microRNAs (miRNAs) after the BM-MSCs treatment in airway allergic inflammation. We induced a mouse model of asthma and performed the transplantation of BM-MSCs.We analyzed aberrant miRNAs and key immune regulators using both miRNA and messenger RNA (mRNA) polymerase chain reaction (PCR) arrays. We identified that 296 miRNAs were differently expressed after the induction of asthma and/or the treatment of BM-MSCs, in which 14 miRNAs presented the reverse variation tendency between asthma induction and BM-MSCs transplantation. Mmu-miR-21a-3p, mmu-miR-449c-5p, and mmu-miR-496a-3p were further confirmed to be differently expressed with additional samples and quantitative real-time PCR. With an mRNA PCR array, we identified 19 genes to be involved in the allergy induction and the administration of BM-MSCs. Further target genes analysis revealed that mmu-miR-21a-3p was significantly correlated with the immune regulator activin A receptor, Type IIA (Acvr2a).Mmu-miR-21a-3p had opposite expression with Acvr2a after asthma and BM-MSCs treatment. Acvr2a had binding sites for miR-21a for bothmice and human, suggesting that miR-21/Acvr2a axis is conserved between human and mice. Dual-luciferase reporter assay showed that mmu-miR-21a-3p negatively regulated the transcript of Acvr2a. In addition, has-miR-21a inhibitor significantly increased the expression of Acvr2a mRNA in BEAS-2B cells under lipopolysaccharide stimulation. Our results suggest that there were different miRNA and mRNA profiles after asthma induction and BM-MSCs treatment, and the miR-21/Acvr2a axis is an important mechanism for the induction of asthmatic inflammation. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer worldwide, and liver metastasis presents a major cause of CRC-associated death. Extensive genomic analysis has provided valuable insight into the pathogenesis and progression of CRC; however, a comprehensive proteogenomic characterization of CRC liver metastasis (CLM) has yet to be reported. Here, we analyzed the proteomes of 44 paired normal colorectal tissues and CRC tissues with or without liver metastasis, as well as analyzed genomics of CRC characterized previously by The Cancer Genome Atlas (TCGA) to conduct integrated proteogenomic analyses. We identified a total of 2,170 significantly deregulated proteins associated with CLM, 14.88% of which were involved in metabolic pathways. The mutated peptide number was found to have potential prognosis value, and somatic variants revealed two metabolism-related genes UQCR5 and FDFT1 that frequently mutated only in the liver metastatic cohort and displayed dysregulated protein abundance with biological function and clinical significance in CLM. Proteogenomic characterization and integrative and comparative genomic analysis provides functional context and prognostic value to annotate genomic abnormalities and affords a new paradigm for understanding human colon and rectal cancer liver metastasis. Keywords: CRC, liver metastasis, proteomics, genomics, integrated analysis