Regulatory T cells (Tregs) characterized by the expression of the master transcription factor forkhead box protein p3 (Foxp3) suppress anticancer immunity, thereby hindering protective ...immunosurveillance of tumours and hampering effective antitumour immune responses in tumour-bearing hosts, constitute a current research hotspot in the field. However, Tregs are also essential for the maintenance of the immune tolerance of the body and share many molecular signalling pathways with conventional T cells, including cytotoxic T cells, the primary mediators of tumour immunity. Hence, the inability to specifically target and neutralize Tregs in the tumour microenvironment without globally compromising self-tolerance poses a significant challenge. Here, we review recent advances in characterizing tumour-infiltrating Tregs with a focus on the functional roles of costimulatory and inhibitory receptors in Tregs, evaluate their potential as clinical targets, and systematically summarize their roles in potential treatment strategies. Also, we propose modalities to integrate our increasing knowledge on Tregs phenotype and function for the rational design of checkpoint inhibitor-based combination therapies. Finally, we propose possible treatment strategies that can be used to develop Treg-targeted therapies.
MicroRNAs are endogenous single-stranded non-coding small RNA molecules that can be secreted into the circulation and exist stably. They usually exhibit aberrant expression under different ...physiological and pathological conditions. Recently, differentially expressed circulating microRNAs were focused on as potential biomarkers for cancer screening. We herein review the role of circulating microRNAs for cancer diagnosis, tumor subtype classification, chemo- or radio-resistance monitoring, and outcome prognosis. Moreover, circulating microRNAs still have several issues hindering their reliability for the practical clinical application. Future studies need to elucidate further potential application of circulating microRNAs as specific and sensitive markers for clinical diagnosis or prognosis in cancers.
Cancer progression is closely related to the tumor microenvironment in which the tumor exists, including surrounding blood vessels, immune cells, fibroblasts, bone marrow‐derived inflammatory cells, ...signaling molecules and the extracellular matrix. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can impact the growth and evolution of cancerous cells. One of major cell components in the tumor microenvironment is myeloid‐derived suppressor cells (MDSCs), which promote tumor growth and metastasis directly or indirectly by recognizing other immune cells, producing cytokines and exerting their immunosuppression functions. MDSCs have emerged as major regulators of immune responses in cancer and key targets for treating cancer. There are many limitations and side‐effect in approaches of conventional cancer therapy, including radiotherapy. It has grown up to be a burgeoning field that a combination of radiotherapy and immunotherapy applied to cancer therapy. Therefore, it is fundamental to explore the immune mechanism in the process of cancer treatment. Here, we reviewed the recent progress of MDSCs in roles of the tumor microenvironment and tumor radiotherapy.
•Two-stage PN-anammox processes were efficient to treat reject water.•53% COD was removed in PN process including oxygen-containing volatile organics, proteins and humic acids.•The effluent COD ...consisted mainly of recalcitrant hydrocarbons.•Organics in reject water stimulated the growth of denitrifying bacteria, Ottowiaand Denitratisoma.
Reject water contains complex components of organic compounds, which have significant influences on the nitrogen removal performance when treated using biological autotrophic nitrogen removal technology. In this study, a two-stage partial nitritation (PN)-anammox (floc-granule) system was established to treat reject water (COD/NH4+-N = 0.97 ± 0.15), and the evolution of organic compounds along PN and annamox bioreactors was investigated using gas chromatography–mass spectrometry and excitation-emission matrix. Also, the variation of PN and anammox sludge properties relating to COD reduction was examined. The PN-anammox system removed approximately 80% of total inorganic nitrogen and COD with hydraulic reaction time of 16 h. The influent organics (330–600 mg COD/L) in reject water were primarily composed of volatile, protein-like and humic acid-like organic compounds. PN process contributed 53 ± 18% of the overall COD removal, primarily including oxygen-containing organics (e.g. phenol), proteins and humic acids. Anammox process contributed 22 ± 15% of the overall COD removal, but large molecule acids (e.g. lactic acid) and small molecule alcohols (e.g. glycerol) were reoccurred, contributing to the effluent COD with recalcitrant hydrocarbons (e.g. n-Octadecane). Reject water increased the extracellular proteins/polysaccharides ratio of PN and anammox sludge, promoting the adsorption and degradation of organic compounds. High-throughput sequencing results showed that denitrifying bacteria of Ottowia increased from 0.03% to 14.4% in PN reactor, and of Denitratisoma increased from 9.6% to 15.4% in anammox reactor. The occurrence of these denitrifiers might mitigate the negative impact of organics to functional organisms. This study highlights the organics fate during PN-anammox treatment system, which is important to maintain the robust nitrogen removal when treating organics-containing and high ammonium concentration wastewater.
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A fiber beam-column element is adopted to simulate the damage development process of reinforced concrete (RC) bridge piers under quasi-static and earthquake loadings considering global buckling and ...low-cycle fatigue of longitudinal bars. The tensile strain and low-cycle fatigue are used to represent the damage to longitudinal bars while the compression strain is adopted to calculate the damage to the cover concrete. A section damage index is proposed based on the material damage definition and bridge performance assessment. A set of circular RC bridge piers tested under different uniaxial quasi-static loading regimes are adopted to verify the reliability of the fiber beam-column element and the proposed damage model. Square RC columns subjected to different uniaxial and biaxial quasi-static loadings are used to verify the applicable scope of the fiber element and the damage index in biaxial quasi-static loading. In addition, a series of shaking table model tests on square, rectangular and circular piers subjected to bilateral earthquake ground motions are simulated to further verify the versatility of this model. The results show that, the fiber beam-column element can simulate RC columns/piers with different sections and loading regimes with good accuracy. The damage index proposed in this paper is compared against experimental results and other damage indices and it is found that the proposed index can reflect the damage state at any stage and the gradual accumulation of damage in RC columns/piers more convincingly than most other indices available in literature.
•Fiber-based modeling of RC bridge piers considering low-cycle fatigue and buckling.•Different quasi-static and earthquake ground motion loading modes are simulated.•A fiber-based damage index is proposed based on material damage.•Tensile strain and low-cycle fatigue are used to calculate longitudinal bars damage.•Spalling extent of cover concrete is used to represent concrete damage.
In order to monitor the accumulation of heavy metals effectively and avoid the damage to the health of agricultural soils, a promising approach is to predict low concentrations of heavy metals in ...soils using visible and near-infrared (VNIR) reflectance spectroscopy coupled with calibration techniques. This study aimed to (i) compare the performance of a combination of partial least squares regression with genetic algorithm (GA-PLSR) against a general PLSR for predicting low concentrations of four heavy metals (i.e., As, Pb, Zn and Cu) in agricultural soils; (ii) explore the transferability of GA-PLSR models defined on one subset of land-use types to the other types; and (iii) to investigate the predictive mechanism for the prediction of the metals. One hundred soil samples were collected in the field locating at Yixing in China, and VNIR reflectance (350–2500nm) spectra were measured in a laboratory. With the entire soil samples, GA-PLSR and PLSR models were calibrated for the four heavy metals using a leave-one-out cross-validation procedure. The GA-PLSR models achieved better cross-validated accuracies than the PLSR models. For the transferability of GA-PLSR models, the soil samples were divided into three pairs of training sets and test sets from different land-use types. Three GA-PLSR models defined on the training sets had good transferability to the test sets, but nine GA-PLSR models were not successful. As for the predictive mechanism, besides the widely-used correlation analysis between OM and the metals, the relationship between the content of OM and the prediction accuracy of the metals was investigated and the similarity of the important wavelengths for OM and the metals was compared. The three methods verified that OM had a significant correlation with the predictions of the spectrally-featureless metals (Pb, Zn and Cu) from VNIR reflectance. We conclude that GA-PLSR modeling has a better capability for the prediction of the low heavy metal concentrations from VNIR reflectance, and it has a potential of transferability between different land-use types, and its accuracy is fundamentally influenced by OM.
•We predicted low contents of soil heavy metals using VNIR reflectance and GA-PLSR.•We predicted heavy metal concentrations of soils covered with nine land-use types.•The transferability of GA-PLSR models between land-use types were explored.•Soil organic matter played a bridge role in estimating Pb, Zn and Cu concentrations.
In the paper, the conservative Fourier spectral scheme is presented for the coupled Schrödinger–Boussinesq equations. We apply the Fourier collocation scheme to spatial derivatives and the ...Crank–Nicolson scheme to the system in time direction, respectively. We find that the scheme can preserve mass and energy conservation laws. Moreover, the existence, uniqueness, stability and convergence of the scheme are discussed, and it is shown that the scheme is of the accuracy
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Heterosis, or hybrid vigor, is exploited by breeders to produce elite high-yielding crop lines, but beneficial phenotypes are lost in subsequent generations owing to genetic segregation. Clonal ...propagation through seeds would enable self-propagation of F
hybrids. Here we report a strategy to enable clonal reproduction of F
rice hybrids through seeds. We fixed the heterozygosity of F
hybrid rice by multiplex CRISPR-Cas9 genome editing of the REC8, PAIR1 and OSD1 meiotic genes to produce clonal diploid gametes and tetraploid seeds. Next, we demonstrated that editing the MATRILINEAL (MTL) gene (involved in fertilization) could induce formation of haploid seeds in hybrid rice. Finally, we combined fixation of heterozygosity and haploid induction by simultaneous editing of all four genes (REC8, PAIR1, OSD1 and MTL) in hybrid rice and obtained plants that could propagate clonally through seeds. Application of our method may enable self-propagation of a broad range of elite F
hybrid crops.
Introduction In recent years, China’s divorce rates have remained high, especially in metropolitan areas such as Beijing and Shanghai, where rates reach up to 40%. Additionally, there has been a ...notable shift towards younger demographics in divorce cases. In a society that highly values marital harmony, divorce is often seen as a cultural transgression. Anthony Giddens’ theory of disembedding and re-embedding provides a useful framework for understanding these changes. This study addresses a gap in literature by focusing on the online social interactions of divorced Chinese youth, exploring their use of dating apps for emotional support and social reconnections. Methods This qualitative study employed semi-structured interviews with 19 divorced young adults in China who engaged with dating apps such as Momo, Tantan, and Soul. Participants were recruited via Douban and Xiaohongshu. The interviews, conducted through WeChat voice calls and Tencent Meetings, lasted 45-70 minutes each. Data was analyzed using Nvivo12 to understand the disembedding and re-embedding processes in their online interactions, exploring themes such as motivations, self-presentation, and the transition from online to offline engagements. Results and discussion The findings reveal that these individuals face societal challenges, biases, and the residual effects of past marriages, leading them to seek refuge in online environments to avoid stigmatization. In digital spaces, they cautiously engage, revealing a lack of confidence through selective self-disclosure. Their goals range from forming same-sex and opposite-sex friendships to seeking new romantic relationships, indicating a nuanced approach to remarriage and challenging stereotypes of dating app users. Re-engaging online, they discover social support and a sense of community, which aids in regaining confidence post-divorce, underscoring the complex interplay between societal influences and individual adaptation strategies in the digital age. The study highlights the unique challenges faced by this demographic, including maintaining anonymity and dealing with societal prejudices. Future research should consider a broader age range and gender differences to provide a more comprehensive understanding of the online behaviors and experiences of divorced individuals.
As obligate anaerobes, anammox bacteria are sensitive to oxygen, which might hinder the maximization of anammox activity. However, there are very few effective strategies to rapidly recover anammox ...activity after its deterioration under exposure of oxygen. In this study, the activity recovery of anammox bacteria encountering dissolved oxygen (DO) exposure (0.2 and 2.0 mg L−1) were compared by three strategies in short-term experiments, nZVI, Fe(II) dosing, and N2 purging. nZVI is more effective in recovering anammox activity with a high DO exposure (2 mg L−1), compared to a low DO exposure (0.2 mg L−1). After inhibiting by 2.0 mg L−1 DO, anammox activity recovery (normalized to the control) was ranked in the order of nZVI (5 mg L−1) addition (63 ± 8.2%) > Fe(II) (5 mg L−1) addition (41 ± 8.0%) >N2 purging (39 ± 4.0%). In contrast to Fe(II) ion additions, the shell structure of nZVI combined with the buffering effect of biomass-extracellular polysaccharide (EPS) prevented the sharp pH variation and excessive dissolved Fe(II)/Fe(III) in solution. Under such circumstances, nZVI addition (5 and 25 mg L−1) increased the intracellular reactive oxygen species (ROS) to a moderate level (<200%), which might be responsible for the better activity recovery of anammox than that of Fe(II) addition and N2 purging. Specifically, 5 mg L−1 nZVI dosage moderately enhanced the intracellular O2− production (∼150% of the control) after scavenging 2.0 mg L−1 DO, and the anammox activity recovered better than that of both 5 and 25 mg L−1 Fe(II) ions additions. However, high dosage nZVI (75 mg L−1) inhibited anammox activity in spite of low or high DO exposure. Our findings elucidate that appropriate amount of nZVI (short-term dosing) can rapidly recover anammox activity when anammox bacteria encountering oxygen exposure accidentally and could be useful in facilitating the robust operation of anammox-based processes.
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•Ranking of anammox recovery was nZVI > Fe(II) >N2 after 2 mg L−1 DO shocks.•Low dose nZVI promotes anammox activity by moderate O2− increase and DO depletion.•High dose of nZVI/Fe(II) inhibits anammox activity by severe O2− increase.•Free Fe(II)/Fe(III) ions regulate intracellular Fenton reaction and O2− level.•Mechanism of intracellular O2− production after adding nZVI/Fe(II) was proposed.
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