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Human breast milk is a source of microorganisms for infants that play an important role in building infant gut health and immunity. The bacterial composition in human breast milk is influenced by lactation time. This study aimed to investigate the influence of lactation time on bacteria in breast milk at the genus level and the species levels of Bifidobacterium and Lactobacillus on days 2-4, 8, 14, and 30. Eighteen individuals were recruited and 60 milk samples were collected. The 16S rRNA gene, and the bifidobacterial groEL and lactobacilli groEL genes were used for amplicon sequencing. The results revealed that the alpha diversities of colostrum and transition 1 (day 8) milk were lower than that of transition 2 (day 14) and mature milk. PCoA analysis showed that bacterial composition in colostrum and transition 1 milk differed from transition 2 and mature milk. A lower relative abundance of Blautia was found in colostrum and transition 1 milk compared with mature milk and lower abundances of Ruminococcus, Dorea, and Escherichia-Shigella were found in transition 1 compared with mature milk. Bifidobacterium ruminantium, Limosilactobacillus mucosae, and Ligilactobacillus ruminis were the predominant species across all four lactation stages, while Bifidobacterium bifidum was lower in transition 1, and Bifidobacterium pseudocatenulatum and Bifidobacterium pseudolongum were higher in transition 1 milk. This study indicated that the bacterial composition in colostrum was more similar to that of transition 1 milk, whereas the bacterial community in transition 2 milk was similar to that of mature milk which suggests that bacterial composition in human breast milk shows stage-specific signatures even within a short period at both genus level and Bifidobacterium and Lactobacillus species levels, providing insights into probiotic supplementation for the nursing mother.

Using wavelet analysis and power density spectrum, we investigate two transient quasi-periodic oscillations (QPOs) observed in MAXI J1535$-$571 observed with Insight-HXMT. The transient QPOs have a centroid frequency of $\sim 10$ Hz with a FWHM $\sim 0.6$ Hz and an rms amplitude $\sim 14\%$. Energy spectra of QPO and non-QPO regimes are also separated and analyzed, and the spectra become softer with higher $E_{cut}$ in the non-QPO regime compared to the QPO regime. Our results suggest that the transient QPOs detected in MJD 58016 and 58017 are still the type-C QPO, and the source remains in its HIMS. The duration of all type-C QPO signals based on wavelet is positively correlated with the mean count rate above $\sim 10$ keV, implying appearance of QPOs in different time scales should be coupled with the corona. The transient QPO properties could be related to the jet or flares, perhaps the partial ejection of the corona is responsible for the disappearance of the type-C QPO., Comment: 10 pages, MNRAS in press

Stationary and mobile power generation systems, as well as those for aero propulsion, continue to rely heavily on gas turbines. Operational envelopes which critically depends on (flame) jet stabilisation mechanisms, such as swirl, are also affected by considerations for emissions control. In this context, the evolving swirling flow domains feature injection of side (peripheral) dilution air. Despite this, the role of side dilution jets on modifying the flow, turbulence, and mixing fields of turbulent bluff-body (BB) stabilised (swirling) annular flows has not been investigated. This study uses three-dimensional simulations, supported with experimental data to establish boundary conditions, to investigate the interaction of side dilution jets (Red = 18,000) with both non-swirling (S = 0) and swirling (S = 0.3) turbulent BB stabilised annular flows (Res = 35,500). Constant Temperature Anemometry (CTA) measurements are conducted to resolve inlet boundary conditions. The Reynolds Stress Model (RSM) and species transport model (isothermal) are used with validations against benchmark datasets. Results show that the introduction of side dilution jets into a confined domain, whether swirling or not, induces (asymmetrical) Peripheral Recirculation Zones (PRZ). However, the strength, length, and location of PRZ varies with swirl and the downstream positioning of side dilution jets (H = 2.6D, 6.6D). Additionally, side dilution jets increase centreline velocity decay for both, non-swirling and swirling BB flows. In terms of turbulence characteristics, addition of side dilution jets leads to significant gains in shear layer turbulence with an increase of 72% and 35% in turbulent kinetic energy for non-swirling and swirling BB flows, respectively. Analysis of the mixing characteristics shows negligible impact of side dilution jets in the upstream region, however, from x/D > 3 considerable improvement in central jet (fuel) mixing is observed.

Supplementary Figure 3 . CD3+ CD8+ PD-1+ Tim-3+ and CD3+ CD8+ CD27- CD28- cells were sorted from SCCHN tissue. Purified cells were then used in an in vitro suppression assays with autologous T cells. Ratios indicate the number of suppressors to responders. Controls are using equivalent numbers of responder cells alone. Responders were labeled with CFSE. BrdU was added during the final 18 hours of culture. Indicated data are representative of at least three independent experiments. Error bars represent SD of replicate wells for each condition.

Supplementary Figure 4 A. Splenocytes from E7-TCRβ transgenic mice were stained with a tetramer for HPV E749-57 (RAHYNIVTF) or a non-specific control tetramer. Cells were gated on CD3+ CD8+. B. Splenocytes from E7-TCRβ mice were stimulated for 7-9 days using HPV E749-57 (RAHYNIVTF) peptide and rhIL-2 (30u/ml). CD8+ T cells were then purfied by magnetic bead purification and used in an in vitro CTL assay using irradiated, labeled or CFSE labeled cells as targets. Ratios are pulsed E7 TCRβ effectors : unlabled control target cells : CFSE-labeled target cells. Wildtype, unlabeled EL4 cells served as negative control targets. C. CD8+ T cells were purified from E7-TCRβ splenocytes using negative magnetic bead selection and transferred into TC-1 tumor bearing mice in the indicated numbers on day 7 after tumor injection. Plot indicates the average tumor size for each group at the indicated timepoints. . D. FACS staining of splenocytes from E7-TCRβ TCR transgenic mice. Arrow indicates the right panel is the CD3+ CD8+ gate from the left panel.

Supplementary Figure 5. Pan T cells were isolated from human patient PBMC or mouse splenocytes using negative magnetic bead selection. Cells were then stained for CD3 CD8 PD-1 and Tim-3 and analyzed by FACS. Dot plots on the left are gated on CD3+ CD8+ cells. Bar graph on the left is representative of five patients or mice.

Supplementary Figure 1 A. Dot plots displaying ungated staining of CD8+ CD27/CD28- T cells FACS sorted from human SCCHN tumor tissue and used in Figure 1D. B. Staining of CD8+ PD-1+ Tim-3+ T cells FACS sorted from dissociated human SCCHN tumor tissue and used in Figure 1E. C. Staining of CD8+ T cells purified from dissociated TC-1 tumors by magnetic bead positive selection using the indicated antibodies. D. Ungated staining of the PD-1+/Tim-3+, PD-1+/Tim-3-, and PD-1-/Tim-3- cells FACS sorted from CD3+ CD8+ T cells in dissociated TC-1 tumors.

Immune-checkpoint blockade enhances antitumor responses against cancers. One cancer type that is sensitive to checkpoint blockade is squamous cell carcinoma of the head and neck (SCCHN), which we use here to study limitations of this treatment modality. We observed that CD8+ tumor-infiltrating lymphocytes (TILs) in SCCHN and melanoma express excess immune checkpoints components PD-1 and Tim-3 and are also CD27−/CD28−, a phenotype we previously associated with immune dysfunction and suppression. In ex vivo experiments, patients' CD8+ TILs with this phenotype suppressed proliferation of autologous peripheral blood T cells. Similar phenotype and function of TILs was observed in the TC-1 mouse tumor model. Treatment of TC-1 tumors with anti–PD-1 or anti–Tim-3 slowed tumor growth in vivo and reversed the suppressive function of multi-checkpoint+ CD8+ TIL. Similarly, treatment of both human and mouse PD-1+ Tim-3+ CD8+ TILs with anticheckpoint antibodies ex vivo reversed their suppressive function. These suppressive CD8+ TILs from mice and humans expressed ligands for PD-1 and Tim-3 and exerted their suppressive function via IL10 and close contact. To model therapeutic strategies, we combined anti–PD-1 blockade with IL7 cytokine therapy or with transfer of antigen-specific T cells. Both strategies resulted in synergistic antitumor effects and reduced suppressor cell function. These findings enhance our understanding of checkpoint blockade in cancer treatment and identify strategies to promote synergistic activities in the context of other immunotherapies.

Supplementary Figure 7. CD3+ CD8+ PD-1+ Tim-3+ T cells were FACS sorted from dissociated TC-1 tumor grown in C57BL/6 mice. Sorted T cells were then stimulated for 12h in vitro in 96-well plates coated with anti-CD3 and anti-CD28. Golgistoptm was added to the culture to arrest vessicle exocytosis. Cells were then permeabilized and stained for IL-10 and IFNγ or isotype control antibodies used at the same concentration.

Supplementary Figure 6. B. Histograms demonstrating PD-L1, PD-L2, or galectin-9 (Gal-9) expression on TC-1 tumor cells (purple) as compared to isotype controls (grey). Top, TC-1 tumors growing in mice were harvested and dissociated into a single cell suspension by collagenase/hyaluronidase digestion prior to staining and FACS analysis. Tumor cells were identified by gating on CD45 negative cells. Bottom, TC-1 cells growing in vitro were stained for the indicated proteins.

This paper documents trends in and examines determinants of stay-at-home motherhood in urban China from 1982 to 2015. China once had the world’s leading female labor force participation rate. Since the economic reforms starting from the early 1980s, however, some mothers have been withdrawing from the labor force due to diminished state support, a rise in intensive parenting, and heightened work-family conflicts. Based on data from the 1982, 1990, and 2000 Chinese censuses, the 2005 mini-census, and the 2006–2015 Chinese General Social Survey, we find mothers’ non-employment increased for every educational group and grew at a much faster rate among mothers than it did among fathers, particularly those with small children. Moreover, the negative relationships between mothers’ education and non-employment, and between mothers’ family income and non-employment weakened overtime. This is possibly due to women with more established resources can better “afford” the single-earner arrangement and also more emphasize the importance of intensive parenting, than their less resourced counterparts. These findings signal the resurgence of a gendered division of labor in urban China.

This paper discusses a novel, compact sound absorption solution with high performance at various frequencies, including low frequencies, achieved through the effective use of Computational Design and Additive Manufacturing (AM). Sound absorption is widely applied for reducing noise and improving room acoustics; however, it is often constrained by conventional design, material properties and production techniques, which offer limited options for customising performance. This research highlights that AM, in combination with computational design tools, can support the development of novel sound-absorbing products with high performance based on the principle of viscothermal wave propagation in prismatic tubes. The potential of these designs was explored via two studies of customised sound-absorbing panels whose performance was measured in a reverberation room. A custom measurement technique was used based on logarithmic sweeps with high-resolution FFT analysis. A comparison of the measurement results with the theory of viscothermal wave propagation indicated good agreement; thus, this study demonstrates the possibility of developing new concepts and design methods for novel room acoustic devices.

We present the results of the neutron star X-ray binary system Cen X-3 performed by $Insight$-HXMT with two observations during 2017 and 2018. During these two observations, the source reached a X-ray luminosity of $\sim 10^{38}$ erg s$^{-1}$ from 2 -- 105 keV. The analysis of the broadband X-ray spectrum reports the presence of two cyclotron resonance scattering features (CRSFs) with the fundamental line at $\sim$ 28 keV and the harmonic line at $\sim 47 $ keV. The multiple lines exist by fittings with different continuum models, like the absorbed NPEX model and a power-law with high energy exponential cutoff model. This is the first time that both fundamental and harmonic lines are detected in Cen X-3. We also show evidence of two cyclotron lines in the phase-resolved spectrum of Cen X-3. The CRSF and continuum spectral parameters show evolution with the pulse profile, and the two line centroid energy ratio does not change significantly and locates in a narrow value range of $1.6-1.7$ over the pulse phase. The implications of the discovering two cyclotron absorption features and phase-resolved spectral properties are discussed., Comment: 8 pages, MNRAS, 2023, 519, 5402-5409

As the state has shifted its priorities towards social harmony and poverty alleviation, this study finds rhetorical resonance, combined with strong lineage solidarity, as an emerging strategy for villages to compete for government resources and investments. By articulating grassroots needs as being in line with local cadres’ performance goals, villages have successfully converted their needs into development proposals and mobilized lineage solidarity to persuade local cadres of the feasibility of such proposals. Drawing on three villages’ school-saving efforts in Fujian province, our fieldwork illustrates how one village retained its school by mobilizing lineage solidarity and converting education into a “model” village project to boost cultural tourism. Others failed to do so and lost their schools. Under the target-based cadre management system, the bottom-up competition for government support is largely shaped by the villages’ pre-existing development and resource structures, which may maximize management efficiency but may also reinforce socioeconomic inequalities between villages.

The global distribution of cropping intensity (CI) is essential to our understanding of agricultural land use management on Earth. Optical remote sensing has revolutionized our ability to map CI over large areas in a repeated and cost-efficient manner. Previous studies have mainly focused on investigating the spatiotemporal patterns of CI ranging from regions to the entire globe with the use of coarse-resolution data, which are inadequate for characterizing farming practices within heterogeneous landscapes. To fill this knowledge gap, in this study, we utilized multiple satellite data to develop a global, spatially continuous CI map dataset at 30 m resolution (GCI30). Accuracy assessments indicated that GCI30 exhibited high agreement with visually interpreted validation samples and in situ observations from the PhenoCam network. We carried out both statistical and spatial comparisons of GCI30 with six existing global CI estimates. Based on GCI30, we estimated that the global average annual CI during 2016–2018 was 1.05, which is close to the mean (1.09) and median (1.07) CI values of the existing six global CI estimates, although the spatial resolution and temporal coverage vary significantly among products. A spatial comparison with two satellite-based land surface phenology products further suggested that GCI30 was not only capable of capturing the overall pattern of global CI but also provided many spatial details. GCI30 indicated that single cropping was the primary agricultural system on Earth, accounting for 81.57 % (12.28×106 km2) of the world's cropland extent. Multiple-cropping systems, on the other hand, were commonly observed in South America and Asia. We found large variations across countries and agroecological zones, reflecting the joint control of natural and anthropogenic drivers on regulating cropping practices. As the first global-coverage, fine-resolution CI product, GCI30 is expected to fill the data gap for promoting sustainable agriculture by depicting worldwide diversity of agricultural land use intensity. The GCI30 dataset is available on Harvard Dataverse: https://doi.org/10.7910/DVN/86M4PO (Zhang et al., 2020).

Numerical simulations have been conducted to identify the dominant mechanism responsible for driving secondary flow motions in horizontal particle-laden pipe flows, based on an analysis of the forces acting on each phase. A four-way coupling Euler–Lagrangian approach was employed, using direct numerical simulations for the gas phase and Lagrangian particle tracking to account for the drag, gravitational and lift forces, together with the interactions that occur for both particle–wall and inter-particle collisions. The four different flow regimes, which had been identified previously as depending on various combinations of flow parameters and are characterised by the secondary flow structures of both the fluid and particle phases, were identified via varying the mass loading alone from $\varPhi _m=0.4$ to $\varPhi _m=1.8$ . The distribution of the divergence of Reynolds stresses was used to help characterise the classes of the secondary fluid flow. This shows that secondary fluid flows of both the first and second kinds can either exist separately or co-exist in such flows. The forces exerted on the fluid phase by the pressure gradient and fluid–particle interactions were examined qualitatively and quantitatively to identify their contribution to the secondary fluid flow motions. A similar study was also applied to the drag, lift and gravitational forces exerted on the particle phase for the secondary particle flow motions. These were found to explain the secondary flows of both the fluid and particle phases with regard to both the flow direction and magnitude, together with the interaction between the two phases.

Following Bourdieu’s classic work on habitus and field, scholars use habitus fit/misfit to distinguish students’ college experience but how students’ experiences habitus misfit and transformation i...

Human breast milk is a source of microorganisms for infants that play an important role in building infant gut health and immunity. The bacterial composition in human breast milk is influenced by lactation time. This study aimed to investigate the influence of lactation time on bacteria in breast milk at the genus level and the species levels of

卵巢成熟性畸胎瘤1%~3%会发生恶变，主要恶变为鳞状细胞癌，少见腺癌、肉瘤和类癌，恶变为黑色素瘤更为罕见，约占0.1%。现报道1例卵巢原发性黑色素瘤合并成熟性畸胎瘤，此肿瘤术前诊断困难，需要术后病理明确诊断，且目前没有既定的治疗指南，预后差。现结合本例的临床病理特征并复习相关文献，对原发性黑色素瘤合并成熟性畸胎瘤进行分析讨论，以提高临床及病理医师对该类肿瘤的认识，避免误诊。.

The data of 33 patients with adult-onset still's disease (AOSD)-associated macrophage activation syndrome (MAS) were retrospectively collected from January 2013 to December 2020 in Peking Union Medical College Hospital. Hemophagocytic lymphohistiocytosis (HLH)-2004 criteria, macrophage activation syndrome/juvenile idiopathic arthritis (MS-Score) and hemophagocytic syndrome diagnostic score (HScore) were used to diagnose AOSD-associated MAS, respectively. The time of diagnosis of AOSD-associated MAS by MS-Score was 19.0 (4.5, 31.0) days [收集2013年1月至2020年12月在北京协和医院出院诊断为成人Still病（AOSD）合并巨噬细胞活化综合征（MAS）的33例患者的临床资料，分析比较分别应用噬血细胞性淋巴组织细胞增多症（HLH）-2004标准、巨噬细胞活化综合征/幼年特发性关节炎评分（MS-Score）和HLH诊断评分（HScore）确诊MAS的时间。结果发现，应用MS-Score确诊MAS的时间［

Coleus (Plectranthus scutellarioides [L.] R.Br.[syn.: Solenostemon scutellarioides]) is a perennial plant in the Lamiaceae family. It produces variegated leaves of various colors. It is commonly cultivated as an ornamental plant or grown in commercial greenhouses (Garibaldi et al. 2019). Phelipanche aegyptiaca Pers. is a dicotyledonous holoparasitic flowering plant that parasitizes more than 30 food crops (e.g., tomato, sunflower, and chickpea), ornamental crops, and others in different parts of the world, causing heavy economic losses (Nosratti et al. 2020). In 2016 and 2017, broomrape was observed parasitizing coleus in the greenhouse (86° 3' 36" E, 44° 18' 36" N, 500 m elevation) in Shihezi, Xinjiang, China (Supplementary Figure 1A-D). A single coleus plant could be parasitized by average 6-10 broomrape plants, and 20% of coleus plants were infested. The infection was confirmed by verifying the attachment of the broomrape to the coleus root. The inflorescences of the broomrape were normal and healthy and produced germinable seeds (germination rate: 80-90%). The morphological characteristics of the coleus are shown in Supplementary Figures 6 and 7. The main botanical features of the broomrape are as follows: (i) stem 20.65±7.07 cm tall, erect, branched, frail, rather hairy, bulbous at the base with secondary roots; (ii) inflorescence usually many-flowered, lax and cylindrical; (iii) bracts 6.87±0.93 mm long, ovate to lanceolate; (iv) calyx 1.09±0.09 cm long, shortly campanulate; (v) corolla 3.38±0.19 cm long, erect to suberect, white at the base, blue-purple in the upper part, sparsely glandular-villous; (vi) stamens 4, filaments inserted 5-6 mm from the base of the corolla, 1.26±0.11 cm long, anthers with villous; (vii) pistil 2.9±0.15 cm long, ovary glabrous, style with short glandular hairs, stigma bilobed, white (Supplementary Figure 2) (Teimoury et al. 2012; Piwowarczyk et al. 2019). For molecular identification, total genomic DNA was extracted from the flowers of the broomrape (found parasitizing coleus plants), and the ribosomal protein S2 (rps2) and ribosomal DNA internal transcribed spacer (ITS) region were amplified by PCR using the primer pairs rps2F/rps2R, ITS1/ITS4 (Table 1) (Park et al. 2007; Anderson et al. 2004). Two sequences with 580 bp (ITS) and 443 bp (rps2) were obtained (GenBank accession No. MW811482 and MW883573). BLAST analysis showed that the ITS sequence was most similar (identity 100%) to P. aegyptiaca (KC811171) and the rps2 sequence (identity 99%) also matched that of P. aegyptiaca (KC814957). Phylogenetic analysis of the ITS regions and rps2 genes showed that broomrape was fallen into P. aegyptiaca groups (Supplementary Figure 3). Morphological and molecular findings strongly support the conclusion that the broomrape on coleus was P. aegyptiaca. In order to verify that coleus was a host of P. aegyptiaca, coleus seedlings were collected and moved to 1.5-L pots containing a mixture of compost-vermiculite-sand (1:1:1 v:v:v) and seeds of P. aegyptiaca harvested from the host coleus (50 mg of P. aegyptiaca seeds per 1 kg of the substrate). Another three coleus seedlings were transplanted into pots of the same size containing the same mixture as above without P. aegyptiaca seeds. These served as controls. After 90 days of inoculation, the leaves of the infected hosts were lighter in color than those of uninfected hosts (Supplementary Figures 4A, 6). The roots of coleus and P. aegyptiaca were carefully washed with water, and an average of 3-4 emerged broomrape shoots and 50-60 underground attachments were observed on coleus roots (Supplementary Figure 4B). P. aegyptiaca can develop normally in the root of the coleus plant, from germination through attachment to host roots and development of tubercles (Supplementary Figure 5 A-E). Longitudinal and transverse sections of the parasite and host roots at the tubercle stage revealed that the endophytic tissues of P. aegyptiaca had reached and connected to the host vascular bundle (Supplementary Figure 5F-I), confirming the normal biological development and function of P. aegyptiaca haustoria. To the best of our knowledge, this is the first report of P. aegyptiaca parasitizing coleus in Xinjiang, China. Coleus is a very widely cultivated horticultural ornamental plant, and it grows in the same environments favored by P. aegyptiaca; so, the plant can aid the transmission of P. aegyptiaca to previously clear regions. It is necessary to improve the management of coleus in places where P. aegyptiaca is prevalent so as to reduce its spread. References: Garibaldi, A., et al. 2019. Plant Dis. 104:590. https://doi.org/10.1094/PDIS-07-19-1399-PDN Crossref, ISI, Google Scholar Nosratti, I., et al. 2020. Weed Sci. 68:555-564. https://doi.org/10.1017/wsc.2020.61 Crossref, ISI, Google Scholar Teimoury, M., et al. 2012. Plant Dis. 96:1232. https://doi.org/10.1094/PDIS-01-12-0068-PDN Crossref, ISI, Google Scholar Piwowarczyk, R., et al. 2019. Phytotaxa. 386:001-106. https://doi.org/10.11646/phytotaxa.386.1.1 Crossref, ISI, Google Scholar Park, J. M., et al. 2007. Mol. Phylogenet. Evol. 43: 974-985. https://doi.org/10.1016/j.ympev.2006.10.011 Crossref, ISI, Google Scholar Anderson, I. C., et al. 2004. Environ. Microbiol. 6: 769-779. https://doi.org/10.1111/j.1462-2920.2004.00675.x Crossref, ISI, Google Scholar.

Patients with deep burns are prone to suffer cicatrix hyperplasia or contracture, leading to problems including dysfunction in limbs, which impacts patients' life quality and makes it difficult for them to return to society. Thereby, the rehabilitation treatment after deep burns is particularly important. Currently, exercise therapy plays an important role in burn rehabilitation, which is mainly based on therapies such as continuous manual assistance training and manual stretching practice to provide patients with physical exercise to limbs and to correct the functional dysfunction of limbs in patients. With the continuous progress in technology, functional training robots have been developed to meet the needs. The emergence of functional training robots saves manpower and provides patients refined and standardized functional exercise treatment. From the aspects of production technology and multi-technology integration, this paper mainly introduces the recent innovation and development of functional training robots and the advantages of the application of functional training robots in the field of burn rehabilitation.深度烧伤患者极易出现瘢痕增生或挛缩，导致肢体功能障碍等问题，严重影响患者生活质量，使其难以回归社会，因此深度烧伤后的康复治疗尤为重要。目前运动疗法在烧伤康复中发挥重要作用，但多以人工持续辅助训练、手法牵伸活动等给予患者肢体活动锻炼，纠正患者肢体功能障碍。随着科技的不断进步，功能训练机器人应运而生。功能训练机器人的出现节约了人力，提供给患者精细、标准化的功能锻炼治疗。该文主要从制作技术与多技术整合方面对目前功能训练机器人的革新发展以及功能训练机器人在烧伤康复领域应用的优势进行介绍。.

1. The role of probiotics in modulating intestinal mucosal immunity in chicks was investigated by measuring migration of intraepithelial lymphocytes (IEL) and cytokine signals in chicks fed on a di...

Introduction: The development and FDA approval of drugs targeting the PD-1/PD-L1 axis has greatly shifted the paradigm of immunotherapy and has improved the clinical outcome for patients diagnosed with advanced melanoma. Despite the recent advancement of immune checkpoint inhibitors, more than 50% of patients still fail to show a sustained response to therapy. Therefore, there is a critical need to develop therapies specific to novel immune targets as well as combination drug regimens. Current immunocompetent preclinical models do not adequately model the responses to immunotherapy, reflecting the urgent need to develop models with greater translational utility. To address this need, we developed a humanized xenograft melanoma model engrafted with autologous peripheral blood lymphocytes (PBLs) to evaluate the utility of nemvaleukin alfa, an engineered IL-2 cytokine which preferentially activates and expands cytotoxic NK cells and antigen-experienced CD8 T cells. Methods: Melanoma-bearing mice were injected intravenously with matched melanoma patient PBLs and treated for four cycles (1 cycle/week) with anti-PD-1, nemvaleukin, or rhIL-2. Tumor growth was monitored, and correlative analyses were done on blood, spleen, and tumors by flow cytometry after 4 cycles of treatment. Results: This humanized melanoma mouse model exhibited good T cell engraftment and was characterized by expression of the proliferative marker Ki-67 in 50-60% of CD8+ and CD4+ T cell populations. Treatment with nemvaleukin resulted in significant tumor growth inhibition rates (TGIs) of an average of 48% compared to vehicle-treated mice. In addition, nemvaleukin promoted expansion of CD8+ and CD4+ T cells, without expansion of CD4+ regulatory T cells, which are known to suppress immunological responses. Compared to rhIL-2 and vehicle, nemvaleukin treatment delayed tumor growth and enhanced survival with a median survival time of 56 days compared to 21 and 50 days, respectively. Nemvaleukin-treated mice had higher CD45+ cell engraftment in spleens and tumors compared to anti-PD-1 treatment, indicating that nemvaleukin boosts T cell proliferation and expansion. Of note, we observed better antitumor efficacy in response to nemvaleukin or anti-PD-1 when mice were engrafted with tumors from patients who responded to checkpoint immunotherapy with TGIs of 36% and 51%, respectively, compared to those who did not with TGIs of 16% and 12%, respectively. These data indicate that treatment responses in our humanized model correlates with clinical outcomes. Conclusion: In this all autologous humanized melanoma mouse model, nemvaleukin treatment not only enhances T cell engraftment, it significantly augments anti-tumor efficacy. These data support the use of this personalized melanoma xenograft model to analyze the underlying immune responses in responders and non-responders to novel immunotherapies. Citation Format: Yee Peng Phoon, Jared E. Lopes, Lukas W. Pfannenstiel, C. Marcela Diaz-Montero, Ye F. Tian, Marc S. Ernstoff, Pauline Funchain, XiaoXia Li, Heather C. Losey, Raymond J. Winquist, Brian R. Gastman. Developing an autologous humanized mouse model to assess responses to novel immunotherapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1818.

For artillery weapons, improving range or improving mobility is an eternal contradiction, so lightweight design is the key method to solve this contradiction. The application of composite material can improve the degree of artillery lightening and enhance the comprehensive combat effectiveness of artillery, so as to adapt to the requirements of modern war. This paper analyzed the characteristics, performances and capable application areas of common-used composite materials in artillery, and introduced its recent applications both home and abroad in barrels, turrets and other structural parts, and focused on the research on design methods and key technologies of its applications in self-propelled artillery. It can be taken as a guide in reasonable application of composite materials in artillery weapons.

Berberine (BBR) is an isoquinoline alkaloid which protects the acute gastroenteritis and inhibits gastric ulcers, and 8-Alkylberberine (8-BBR-Cn, n=4, 8, 12 and 16) with a long aliphatic chain are synthesized have been reported. This paper investigated the possible mechanisms underlying the gastroprotective effect of 8-BBR-Cn derivatives at dose of 25, 50 and 100 mg/kg body weight on enthanol-induced gastric mucosal injury in rats. The ulcer index and percentage inhibition were evaluated. The stomachs tissues were chosen for determination of nitric oxide synthase (NOS) activity and prostaglandin E2 (PEG2) levels, and assay kit were used for the above two assays. Compared with model control group, the ulcer indexes of 8-BBR-Cn (25, 50 and 100 mg/kg, i.g.) treatment groups decreased significantly. Additionally, 8-BBR-Cn could enhance PEG2 concentration in mucosal tissue of gastric ulcer rats. Moreover, in mucosal tissue, activities of total NOS (TNOS) and constitutive NOS (cNOS) were increased, but inducible NOS (iNOS) was decreased by 8-BBR-Cn. 8-BBR-Cn derivatives had protective effect on gastric mucous membrane, and 8-BBR-C16 displayed stronger gastroprotective effect as carbon chain at C8 position lengthens, which was related to prostaglandin E2 and nitric oxide synthase pathways.

Dental pulp stem cells (DPSCs) are adult stem cells of neural crest origin, are readily available, have good self-renewal and multidirectional differentiation properties, can differentiate into a variety of cells, are abundant, less harmful to donate, have no ethical issues, low immunogenicity, and therefore, are widely used as seed cells in the field of tissue engineering and regenerative medicine. MicroRNA (miRNA) is a single-stranded non-coding small RNA consisting of about 22 nucleotides, which plays an important regulatory role in various aspects of cellular activities, such as proliferation, differentiation, and apoptosis. In this paper, we review the regulatory role of small RNA in the differentiation of DPSCs and its mechanism in the past 5 years. This paper aims to reveal the important role of miRNAs in differentiation in DPSCs.MicroRNAs (miRNAs), differentiation, and DPSCs were extensively searched in three databases from 2014 to 2021. These databases include PubMed, Cochrane Library, Embase.Our study reviews the microRNAs (miR-145, miR-143-3p, miR-140-5p, miR-488, miR-218, miR-125a-3p, miR-27a-5p, miR-223, miR-21, miR-143, miR-215, miR-219a-1-3p, miR-31, miR-496, miR-218, miR-24-3p, miR-146a-5p, miR-196a, miR-188-3p, miR-424, miR-378a, miR-135, miR-124) in the differentiation of DPSCs.A large body of evidence supports the involvement of miRNAs in differentiation associated with mesenchymal stem cells (MSCs), although the mechanisms involved are not yet clear. Most of the current studies are from in vitro studies, but the ultimate goal is to apply these studies to the clinic, and studies involving in vivo models are needed.

In this article, an exponential high-order compact (EHOC) difference method is introduced for solving the convection-dominated convection diffusion problems on nonuniform grid without any c...

To identify the critical genes and pathways that related to OP development in male AS patients, bioinformatic gene analysis and qRT-PCR validation were performed. SBNO2 and VPS13B were identified as the potential target for OP development, which may be valuable for the prevention of OP in male AS patients. Osteoporosis (OP) is common in men with ankylosing spondylitis (AS). The specific pathogenesis of OP in AS, however, is still unclear. The present study attempted to identify potential genes associated with the development of OP in males with AS. Gene expression profiles were downloaded from the GSE73754 and GSE35959 datasets from the Gene Expression Omnibus (GEO). Data from OsteoporosAtlas were downloaded as a supplement. Differentially expressed genes (DEGs) were determined with the limma package. The overlapping DEGs between male AS-related genes and OP-related genes were determined. The DEGs were validated by qRT-PCR in the blood samples of males with AS. Weighted gene co-expression network analysis (WGCNA) was utilized to establish a co-expression network to identify the hub genes. A total of 17 overlapping DEGs were identified; 6 genes in 17 overlapping DEGs were verified as the essential genes in the pathogenesis of OP in male AS by qRT-PCR analysis. After WGCNA, the modules of MEblue (> 0.6) and MEred (> 0.8) were screened out by the correlation analysis and were determined to function mainly in MAPK signaling pathway and osteoclast differentiation. Analysis of the two modules revealed VPS13B and SBNO2 as key genes due to the high degree of correlation. Both genes play an important role in bone metabolism regulation in male AS. Two hub genes MYD88 in MEblue and NCK1 in MEred with high degree of connectivity were selected. Gender-specific SBNO2 and VPS13B may be key genes involved in OP in male AS.

This article provides an outline of the classification of the kingdom Fungi (including fossil fungi. i.e. dispersed spores, mycelia, sporophores, mycorrhizas). We treat 19 phyla of fungi. These are Aphelidiomycota, Ascomycota, Basidiobolomycota, Basidiomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Entorrhizomycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota. The placement of all fungal genera is provided at the class-, order- and family-level. The described number of species per genus is also given. Notes are provided of taxa for which recent changes or disagreements have been presented. Fungus-like taxa that were traditionally treated as fungi are also incorporated in this outline (i.e. Eumycetozoa, Dictyosteliomycetes, Ceratiomyxomycetes and Myxomycetes). Four new taxa are introduced: Amblyosporida ord. nov. Neopereziida ord. nov. and Ovavesiculida ord. nov. in Rozellomycota, and Protosporangiaceae fam. nov. in Dictyosteliomycetes. Two different classifications (in outline section and in discussion) are provided for Glomeromycota and Leotiomycetes based on recent studies. The phylogenetic reconstruction of a four-gene dataset (18S and 28S rRNA, RPB1, RPB2) of 433 taxa is presented, including all currently described orders of fungi., Nalin N. Wijayawardene thanks Mushroom Research Foundation and National Science Foundation of China (No. NSFC 31950410558) for financially supporting this project. Kevin D. Hyde acknowledges the Foreign Experts Bureau of Yunnan Province, Foreign Talents Program (2018; grant no. YNZ2018002), Thailand Research grants entitled Biodiversity, phylogeny and role of fungal endophytes on above parts of Rhizophora apiculata and Nypa fruticans (grant no: RSA5980068), the future of specialist fungi in a changing climate: baseline data for generalist and specialist fungi associated with ants, Rhododendron species and Dracaena species (grant no: DBG6080013), Impact of climate change on fungal diversity and biogeography in the Greater Mekong Subregion (grant no: RDG6130001). H.T. Lumbsch thanks support by the Grainger Bioinformatics Center. E. Malosso is grateful to CAPES for financial support (grant no. 88881.062172/2014-01). B.T. Goto, G.A. Silva and K. Jobim, L.C. Maia acknowledges CNPq (Brazilian Scientific Council, grants no. 465.420/2014-1, 307.129/2015-2 and 408011/2016-5) and CAPES for support. The study was partially supported by the National Science Centre, Poland, under Grants No. 2015/17/D/NZ8/00778 and 2017/25/B/NZ8/00473 to Julia Pawłowska. The research of Martin Kukwa received support from the National Science Centre (NCN) in Poland (project no 2015/17/B/NZ8/02441). Alan J.L. Phillips acknowledges the support from UID/MULTI/04046/2019 Research Unit grant from FCT, Portugal to BioISI. H. Zhang is financially supported by the National Natural Science Foundation of China (Project ID: NSF 31500017). S. Boonmee would like to thank the Thailand Research Fund (Project No. TRG6180001). Dong-Qin Dai and Li-Zhou Tang would like to thank the National Natural Science Foundation of China (No. NSFC 31760013, NSFC 31260087, NSFC 31460561), the Scientific Research Foundation of Yunnan Provincial Department of Education (2017ZZX186) and the Thousand Talents Plan, Youth Project of Yunnan Provinces for support. R. Phookamsak, M. Doilom, D. N. Wanasinghe, S.C. Karunarathna and J.C. Xu express sincere appreciations to Key Research Program of Frontier Sciences of the Chinese Academy of Sciences (grant no. QYZDY-SSW-SMC014) for research financial support. R. Phookamsak thanks the Yunnan Provincial Department of Human Resources and Social Security (grant no. Y836181261), Chiang Mai University and National Science Foundation of China (NSFC) project code 31850410489 for research financial support. S.C. Kaunarathna thanks CAS President’s International Fellowship Initiative (PIFI) for funding his postdoctoral research (No. 2018PC0006) and the National Science Foundation of China (NSFC) for funding this work under the project code 31851110759. S. Tibpromma would like to thank the International Postdoctoral Exchange Fellowship Program (number Y9180822S1), CAS President’s International Fellowship Initiative (PIFI) (number 2020PC0009), China Postdoctoral Science Foundation and the Yunnan Human Resources, and Social Security Department Foundation for funding her postdoctoral research. Yuri S. Tokarev, Elena S. Nassonova and Irma V. Issi are indebtful to Yuliya Y. Sokolova (Institute of Cytology RAS, St. Petersbug, Russia) and Anastasia V. Simakova (Tomsk State University, Tomsk, Russia) for kind permission of reproduction of electron microscopy images of Metchnikovella incurvata and Crepidulospora beklemishevi, respectively. Yuri S. Tokarev and Irma V. Issi thank Russian Foundation of Basic Research, grant number 17-04-00871 (taxonomy of Rozellomycota). Elena S. Nassonova thank Russian Foundation of Basic Research, grant number 18-04-01359 (early evolution of Microsporidia, phylogeny of Metchnikovellida). Adam Flakus and Pamela Rodriguez-Flakus are greatly indebted to all staff of the Herbario Nacional de Bolivia, Instituto de Ecología, Universidad Mayor de San Andrés, La Paz and the SERNAP (http://sernap.gob.bo), for their generous cooperation providing permits, assistance and facilities support for scientific studies. The research of AF and PRF were financially supported by the National Science Centre (NCN) in Poland (DEC-2013/11/D/NZ8/03274). Adam Flakus and Pamela Rodriguez-Flakus received additional support under statutory funds from the W. Szafer Institute of Botany, Polish Academy of Sciences, Krakow, Poland. The authors would like to thank Yunnan Innovation Platform for Development and Utilization of Symbiotic Fungi Resources for finance support. Li-Fang Zhang would like to thank grant-in-aid from Science and Technology Department of Yunnan Province (2018FD080) for finance support. Chun-Ying Deng thanks the Biodiversity Survey and Assessment Project of the Ministry of Ecology and Environment, China (2019HJ2096001006). Yingqian Kang would like to thank Guizhou Scientific Plan Project [(2019) 2873]; Excellent Youth Talent Training Project of Guizhou Province [(2017) 5639]; Guiyang Science and Technology Project [(2017) No. 5-19]; Talent Base Project of Guizhou Province, China [FCJD2018-22]; Research Fund of Education Bureau of Guizhou Province, China [(2018) 481]. D. N. Wanasinghe would like to thank the CAS President’s International Fellowship Initiative (PIFI) for funding his postdoctoral research (number 2019PC0008), the National Science Foundation of China and the Chinese Academy of Sciences for financial support under the following grants: 41761144055, 41771063 and Y4ZK111B01. Yuri K. Novozhilov and Oleg N. Shchepin acknowledge support from the Russian Foundation of Basic Research, project 18-04-01232 А. Ivana Kušan, Neven Matočec, Armin Mešić and Zdenko Tkalčec are grateful to Croatian Science Foundation for their financial support under the project grant HRZZ-IP-2018-01-1736 (ForFungiDNA). K. Tanaka would like to thank the Japan Society for the Promotion of Science (JSPS 19K06802)

In order to avoid the measurement error brought by heating before aerodynamic heating tests in a hypersonic wind tunnel, it’s essential that the testing model should be insert into the flow field quickly. This paper presents a novel fast-moving device driven by a hydraulic system which was based on gas-liquid boosting cylinder and servo proportional valve. The control system of the fast-moving device has adopted IPC centralized-control, electro-hydraulic servo, AC servo and industrial field bus technologies, so mutual independent multiple freedom motion control circuits have been built. By using the high-speed data acquisition and analog output, reading CPU work frequency etc., the control system has solved the difficult question of fast insertion and timing. A series of experimental results show the device satisfies the speed and impact requirements, which can move the testing model into the flow field quickly during aerodynamic heating tests and operate stably.

Hepatoblastoma (HB) is a malignant liver tumor that occurs during childhood. The histone deacetylase SIRT6 functions as a tumor suppressor in diverse cancers. Quercetin, as activators and antioxidants of sirtuins, exhibits remarkable anticancer activity in many tumors. However, whether quercetin ameliorates HB is still unclear. In our study, we found that SIRT6 was downregulated in HB tissues and cell lines. Overexpression of SIRT6 observably suppressed cell proliferation and invasion, promoted cell apoptosis. Mechanistically, SIRT6 suppressed frizzled 4 (FZD4) transcription by deacetylating histone H3K9. Upregulation of SIRT6 reduced the protein levels of FZD4 and H3K9ac. Additionally, quercetin treatment could enhance the expression of SIRT6, repress FZD4 level, cell viability and invasion, and promote apoptosis. Overexpression of FZD4 signally reversed quercetin-treated the promotion effect on cell apoptosis, and the inhibition effects on FZD4 expression, cell viability, invasion and Wnt/β-catenin pathway related proteins. In addition, LiCl, an agonist of Wnt/β-catenin pathway, could recover the inhibition effects of quercetin on Wnt/β-catenin pathway related proteins, cell viability and invasion, and promotion effect on cell apoptosis. In vivo mouse xenograft tumor growth assay revealed that quercetin markedly suppressed tumor growth. In conclusion, these results demonstrated that the molecular mechanism of quercetin suppressing HB cell proliferation and invasion, promoting apoptosis was to promote the deacetylation of SIRT6 on FZD4 and inhibit the activation of Wnt/β-catenin pathway.

Prevailing research on assortative mating marginalizes the agency of third parties. Yet, in China, an intergenerational perspective may be useful because family members have participated in spouse ...