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The global bond market is greater than the global equity market meanwhile it grows gradually in recent years. Issuing corporate bonds is an ideal channel for enterprises to raise funds in the course of COVID-19 and also provides resilience in the market. Moody's, Standard & Poor's and Fitch are well-known global credit rating agencies and suggest investors purchasing investment-grade bonds for reasonable risks and returns. But local credit rating agencies have limited capacities to appraise local bonds. In the COVID-19 crisis, widen yield spreads represent likelihood of default which can be a measure of credit risk. Besides, government interventions (i.e., Quantitative Easing Program) can effectively eliminate credit risks and Confucian culture is a factor in assessing credit risks of corporate bonds. As for liquidity risk, Chinese bond market is less liquid than the US bond market and financial bonds are the most liquid in the Chinese market. The liquidity risk is caused by inaccurate information and market risk tolerance whereas market risk tolerance integrates credit and liquidity, the main measurement of liquidity risk is transaction cost which means that higher transaction cost can impede liquidity in the bond market. Finally, market risk comprises of COVID-19 pandemic, market design and biodiversity risk. The epidemic tightens the financial condition of developing countries and depreciates the currency of the bond market which raises term structure of interest rate up. A well-designed financial market system can help stabilize fluctuations during financial crisis. Besides, biodiversity risk is relevant to the operation apartment of companies.

The structure of international trade has a significant impact on the environment, so effective measures should be taken to control the environmental pollution caused by international trade. Therefore, it is necessary to do a good job in the research on the impact of international trade structure on the environment. This paper chooses international trade as the starting point, analyzes the influence of international trade structure on domestic ecological environment, and gives some countermeasures in combination with specific conditions, so as to realize ecological environment protection on the basis of promoting the development of international trade and avoid the old road of sacrificing the environment for economic development. It is hoped that the relevant discussion in this paper can provide reference for similar research.

Endometriosis is a gynaecological condition characterized by the growth of endometrium-like tissues within and outside of the pelvic cavity. Recent studies have demonstrated that aberrant infiltration of M2 macrophages is mainly responsible for the establishment of endometriotic lesions. A growing body of evidence shows that glycolysis and lactate accumulation have great impact on the regulation of immunomicroenvironment. However, the communication signal between glycolysis and macrophages is poorly defined in endometriosis. Hereby, we investigate the correlation between glycolysis and M2 macrophage infiltration in endometriosis. Next, we confirm that lactate is pivotal factor that drives macrophage M2-polarization to promote endometriotic stromal cells invasion in vitro and in vivo. In addition, we also identify that the activation of Mettl3 and its target gene Trib1 promote M2 macrophage polarization. Moreover, we also demonstrate that Trib1 induce M2 macrophage polarization via the activation of ERK/STAT3 signalling pathway. Finally, by injecting 2-DG into endometriosis mice model, we show that the restrain of glycolysis significantly reduces the progression of endometriosis, which provides evidence for lactate as a potential therapeutic strategy for the prevention and treatment of endometriosis.

Dermal fibroblasts and cutaneous nerves are important players in skin diseases, while their reciprocal roles during skin inflammation have not been characterized. Here we identify an inflammation-induced subset of papillary fibroblasts that promotes aberrant neurite outgrowth and psoriasiform skin inflammation by secreting the extracellular matrix protein tenascin-C (TNC). Single-cell analysis of fibroblast lineages reveals a Tnc+ papillary fibroblast subset with pro-axonogenesis and neuro-regulation transcriptomic hallmarks. TNC overexpression in fibroblasts boosts neurite outgrowth in co-cultured neurons, while fibroblast-specific TNC ablation suppresses hyperinnervation and alleviates skin inflammation in male mice modeling psoriasis. Dermal γδT cells, the main producers of type 17 pathogenic cytokines, frequently contact nerve fibers in mouse psoriasiform lesions and are likely modulated by postsynaptic signals. Overall, our results highlight the role of an inflammation-responsive fibroblast subset in facilitating neuro-immune synapse formation and suggest potential avenues for future therapeutic research.

We explored a new artificial intelligence-assisted method to assist junior ultrasonographers in improving the diagnostic performance of uterine fibroids and further compared it with senior ultrasonographers to confirm the effectiveness and feasibility of the artificial intelligence method. In this retrospective study, we collected a total of 3870 ultrasound images from 667 patients with a mean age of 42.45 years ± 6.23 [SD] for those who received a pathologically confirmed diagnosis of uterine fibroids and 570 women with a mean age of 39.24 years ± 5.32 [SD] without uterine lesions from Shunde Hospital of Southern Medical University between 2015 and 2020. The DCNN model was trained and developed on the training dataset (2706 images) and internal validation dataset (676 images). To evaluate the performance of the model on the external validation dataset (488 images), we assessed the diagnostic performance of the DCNN with ultrasonographers possessing different levels of seniority. The DCNN model aided the junior ultrasonographers (Averaged) in diagnosing uterine fibroids with higher accuracy (94.72% vs. 86.63%, P

The reflection and radiation of steep-fronted wavefronts at a tunnel exit to a deep cutting is studied and contrasted with the more usual case of radiation from over-ground portals. A well-known difference between radiation in odd and even dimensions is shown to have a significant influence on reflected wavefronts, notably causing increased distortion that complicates analyses, but that can have practical advantages when rapid changes are undesirable. Likewise, micro-pressure waves radiating from the portal into a cutting are shown to exhibit strong dispersion that does not occur in the corresponding radiation into an open terrain. In the latter case, formulae that represent the behaviour of monopoles and dipoles are commonly used to estimate conditions beyond tunnel portals, but no such simple formula exists (or is even possible) for cylindrical radiation that is characteristic of MPWs in cuttings. An important outcome of the paper is the development of an approximate relationship that predicts the maximum amplitudes of these MPWs with an accuracy that should be acceptable in engineering design, at least for initial purposes. The formula shows that peak pressure amplitudes decay much more slowly than those from an overground portal, namely varying approximately as r −0.5 compared with r −1, where r denotes the distance from the portal.

Regulatory T (Treg) cells constitute a dynamic population that is critical in autoimmunity. Treg cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities. However, recent studies demonstrated that certain inflammatory conditions induce Treg cell instability with diminished FoxP3 expression and convert them into pathogenic effector cells. Therefore, the identification of novel targets crucial to both Treg cell function and plasticity is of vital importance to the development of therapeutic approaches in autoimmunity. In this study, we found that conditional Pp6 knockout (cKO) in Treg cells led to spontaneous autoinflammation, immune cell activation, and diminished levels of FoxP3 in CD4+ T cells in mice. Loss of Pp6 in Treg cells exacerbated two classical mouse models of Treg-related autoinflammation. Mechanistically, Pp6 deficiency increased CpG motif methylation of the FoxP3 locus by dephosphorylating Dnmt1 and enhancing Akt phosphorylation at Ser473/Thr308, leading to impaired FoxP3 expression in Treg cells. In summary, our study proposes Pp6 as a critical positive regulator of FoxP3 that acts by decreasing DNA methylation of the FoxP3 gene enhancer and inhibiting Akt signaling, thus maintaining Treg cell stability and preventing autoimmune diseases.

Pathway analysis is a popular method aiming to derive biological interpretation from high-throughput gene expression studies. However, existing methods focus mostly on identifying which pathway or pathways could have been perturbed, given differential gene expression patterns. In this paper, we present a novel pathway analysis framework, namely rPAC, which decomposes each signaling pathway route into two parts, the upstream portion of a transcription factor (TF) block and the downstream portion from the TF block and generates a pathway route perturbation analysis scheme examining disturbance scores assigned to both parts together. This rPAC scoring is further applied to a cohort of gene expression data sets which produces two summary metrics, “Proportion of Significance” (PS) and “Average Route Score” (ARS), as quantitative measures discerning perturbed pathway routes within and/or between cohorts. To demonstrate rPAC’s scoring competency, we first used a large amount of simulated data and compared the method’s performance against those by conventional methods in terms of power curve. Next, we performed a case study involving three epithelial cancer data sets from The Cancer Genome Atlas (TCGA). The rPAC method revealed specific pathway routes as potential cancer type signatures. A deeper pathway analysis of sub-groups (i.e., age groups in COAD or cancer sub-types in BRCA) resulted in pathway routes that are known to be associated with the sub-groups. In addition, multiple previously uncharacterized pathways routes were identified, potentially suggesting that rPAC is better in deciphering etiology of a disease than conventional methods particularly in isolating routes and sections of perturbed pathways in a finer granularity.

PurposeTo develop and assess a deep convolutional neural network (DCNN) model for the automatic detection of bone metastases from lung cancer on computed tomography (CT)MethodsIn this retrospective study, CT scans acquired from a single institution from June 2012 to May 2022 were included. In total, 126 patients were assigned to a training cohort (n = 76), a validation cohort (n = 12), and a testing cohort (n = 38). We trained and developed a DCNN model based on positive scans with bone metastases and negative scans without bone metastases to detect and segment the bone metastases of lung cancer on CT. We evaluated the clinical efficacy of the DCNN model in an observer study with five board-certified radiologists and three junior radiologists. The receiver operator characteristic curve was used to assess the sensitivity and false positives of the detection performance; the intersection-over-union and dice coefficient were used to evaluate the segmentation performance of predicted lung cancer bone metastases.ResultsThe DCNN model achieved a detection sensitivity of 0.894, with 5.24 average false positives per case, and a segmentation dice coefficient of 0.856 in the testing cohort. Through the radiologists-DCNN model collaboration, the detection accuracy of the three junior radiologists improved from 0.617 to 0.879 and the sensitivity from 0.680 to 0.902. Furthermore, the mean interpretation time per case of the junior radiologists was reduced by 228 s (p = 0.045).ConclusionsThe proposed DCNN model for automatic lung cancer bone metastases detection can improve diagnostic efficiency and reduce the diagnosis time and workload of junior radiologists.

Diabetes and its complications represent a great burden on the global healthcare system. Diabetic complications are fundamentally diseases of the vasculature, with endothelial cells being the centerpiece of early hyperglycemia-induced changes. Endothelial-to-mesenchymal transition is a tightly regulated process that results in endothelial cells losing endothelial characteristics and developing mesenchymal traits. Although endothelial-to-mesenchymal transition has been found to occur within most of the major complications of diabetes, it has not been a major focus of study or a common target in the treatment or prevention of diabetic complications. In this review we summarize the importance of endothelial-to-mesenchymal transition in each major diabetic complication, examine specific mechanisms at play, and highlight potential mechanisms to prevent endothelial-to-mesenchymal transition in each of the major chronic complications of diabetes.

The track state detection is of great significance to timely understand the operation state of track and find track defects and prevent operation accidents. This article initially analyzes the key technologies of track detection system and then proposes an image detection technology and image processing method for analyzing track detection at home and abroad, thus putting forward the scheme of track detection using image processing. The characteristics of onsite track images are analyzed, and a track state detection system based on track image preprocessing, image position correction, image defect comparison, and track section size measurement is designed in this article. Further in this article, a study of image linear transformation, noise filtering, defect recognition, and edge detection in track image processing is applied. Furthermore, a robust piecewise linear transformation is designed using the combination of image threshold transformation and image gray transformation. It reduces the loss of detailed information in the process of image processing. The center point of track bright band is determined by the image region segmentation method, which effectively reduces the error of image track measurement and improves the measurement accuracy.

Covid-19 causes hundreds of deaths globally meanwhile it brings higher volatility on Hong Kong Stock Market which is the financial center of Asia. It attracts to investigate whether Asset Pricing Models, Prospect Theory and Covid-19 Pandemic can clearly illustrate variations in stocks returns on the market via a set of regression analysis. The empirical findings demonstrate that Hong Kong Stock Market experiences large fluctuations during the pandemic; Hang Seng Index positively relates to constructed portfolios; Government interventions such as Lockdown and Traveling Restrictions bring higher returns on the index; Crude Oil is another factor that affects the stock market negatively; Stocks with the highest previous monthly returns tend to have higher returns in the current month; Asset Pricing Models can provide assistance on assessing whether market efficiency exists in Hong Kong Stock Market.

Haidilao has created a model for China's catering service industry. From corporate management to brand building, it embodies its indelible emotional marketing. This article analyzes the development of Haidilao and investigates the methods for how to satisfy the customers. This research captures the detailed behavior of Haidilao to keep more customers participation. Then, this study establishes the SWOT model to Haidilao and giving insights about Strengths, Weaknesses, Opportunities, and Threats. This article also introduces the most opportunity for this firm is that with the development of society, China's economy has developed rapidly. This would bring many new urban people and mobile people emerging and catering industry products. In the future, more quantitative analysis will be conducted for the company's business development.

ObjectiveThis study aimed to perform a cluster analysis of symptoms linked with Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) and to identify which cluster of symptoms was associated with a higher risk of NG and CT.Study designFrom 15 April to 16 May 2018, a cross-sectional study was conducted, and patients attending sexually transmitted infections (STI) related clinics were recruited from 22 medical institutions in six districts of Shenzhen city.MethodsA structured questionnaire was used to collect social-demographic information as well as STI symptoms, and urine samples were collected for nucleic acid detection. Cluster analysis and logistic regression were applied.ResultsAmong 8,207 participants, the prevalence of CT and NG infection was 9.04% (742/8,207) and 2.36% (194/8,207), respectively. Among male outpatients, four clusters with distinct symptomatic patterns were identified. Unmarried, having casual sexual partners in the past 6 months, cluster 2 (OR = 6.70, 95% CI = 3.36–13.35) and cluster 4 (OR = 24.53, 95% CI = 12.96–46.44) were risk factors associated with NG infection. Unmarried, cluster 2 (OR = 2.54, 95% CI = 1.83–3.53) and cluster 4 (OR = 3.31, 95% CI = 2.37–4.61) were risk factors associated with CT infection. Among female outpatients, five clusters with distinct symptomatic patterns were identified. Aged 24 years or below and cluster 3 (OR = 3.68, 95% CI = 1.61–8.39) were risk factors associated with NG infection. Aged 24 years or below, unmarried, having a high school/secondary technical school education, and having junior high school or below education were risk factors associated with CT infection.ConclusionThe cluster of symptoms integrated into risk assessment for CT and NG infections suggests a new strategy of symptomatic management. Healthcare providers in STI clinics and resource-limited places may use this strategy to identify more potential patients and deliver adequate, acceptable, and equitable STI care for outpatients with a high risk of STI.

Cu2O has been intensively studied as an efficient catalyst for CO2 reduction reaction (CO2RR). By various methods for fine-tuning the morphology and surface modification, high selectivity and activity of different products can be achieved. Here, we report a novel Cu2O nanostructure design by facet-controlled etching, during which the catalyst structure switched from a cuboctahedron architecture to a hollow dice-like structure. The as-etched catalysts exhibit a high Faradic efficiency of formic acid, reaching 75.1% at a low potential of -1.0 V. Further characterizations indicate that the performance enhancement is attributed to the increased oxygen vacancies induced by the etching process. Our Cu2O nanostructure design provides a new approach for high-efficiency catalysts for formic acid production at low potentials.

Male crickets attract females by producing calls with their forewings. Louder calls travel further and are more effective at attracting mates. However, crickets are small, and therefore inefficient, dipole sound-sources. Only a small group called tree crickets make acoustic tools called baffles which reduce acoustic short-circuiting, a source of dipole inefficiency. Here, we ask why baffling is uncommon among crickets. We hypothesize that baffling may be rare, because like other tools they offer insufficient advantage for most species. To test this, we modelled the calling efficiencies of crickets within the full space of possible natural wing sizes and call frequencies, in multiple acoustic environments. We then generated efficiency landscapes, within which we plotted the positions of 111 cricket species across 7 phylogenetic clades. We found that all sampled crickets, in all conditions, could gain efficiency from tool use. Surprisingly, however, we also found that calling from the ground significantly increased efficiency, with or without a baffle, by as much as an order of magnitude. We found that the ground provides some reduction of acoustic short-circuiting but also halves the air volume within which sound is radiated. It simultaneously reflects sound upwards, allowing recapture of a significant amount of acoustic energy through constructive interference. Thus, using the ground as a reflective baffle is a very effective strategy for increasing calling efficiency. Indeed, theory suggests that this increase in efficiency is accessible not just to crickets, but to all acoustically communicating animals whether they are dipole or monopole sound sources.Significance StatementLoudness is a crucial functional feature of calls in acoustically communicating animals. Animals attempting to reach prospective mates or ward off predators are expected to make themselves as loud as possible. Given the importance of loudness, there are two long-standing, seemingly unrelated paradoxes in acoustic communication. The first is the rarity of acoustic tool use. The second is the high number of animals that call from reflective surfaces, like the ground, known be an impediment to sound propagation. We resolve both paradoxes and show them to be related. By refocusing analysis from sound propagation to sound radiation, we show that the ground is the opposite of an impediment and can, in fact, boost sound loudness more than tool use. Thus, we show that calling from a reflective surface is an alternative strategy for maximizing call loudness, and one that is available to all animals.

The photosystem II (PSII) outer antenna OsLHCB3 protein plays critical roles in binding PSII chlorophyll, absorbing sunlight and transfering the excitation energy for photosynthesis. Here, OsLHCB3 knockdown mutants were produced using the RNAi system. Phenotypic analyses showed that OsLHCB3 knockdown led to pale green leaves and lower chlorophyll contents at both tillering and heading stages. In addition, mutant lines exhibited decreased non-photochemical quenching (NPQ) capacity and net photosynthetic rate (Pn) by downregulating the expression of PSII-related genes. Moreover, RNA-seq experiments were performed at both tillering and heading stages. The diferentially expressed genes (DEGs) mainly involved in chlorophyll binding, response to abscisic acid, photosystem II, response to chitin, and DNA-binding transcription factor. Besides, our transcriptomic and physiological data indicated that OsLHCB3 was essential for binding chlorophyll, but not for the metabolism of chlorophyll in rice. OsLHCB3 RNAi knockdown plants affected the expression of PS II-related genes, but not PS I-related genes. Overall, these results suggest that OsLHCB3 also plays vital roles in regulating photosynthesis and antenna proteins in rice as well as responses to environment stresses.

Controlling the virus spreading in complex networks is very important to the research fields ranging from social science to technology. However, recent researches only consider information transmission and virus spreading as independent and uncorrelated, which neglect their interactive process in real systems. To study the interactive process between information transmission and virus spreading, in this paper, we propose a new virus information interactive spreading model on multiplex network. The multiplex networks can be divided into information transmission layer and virus spreading layer. The interactive spreading model considers the inherent characteristics of information by introducing the information forgetting and information loss mechanisms. Specially, by utilizing the mean field theory, the information transmission and virus process are unified to deduce the critical threshold of virus breakout. It shows that the critical threshold is not only related to the spreading properties of virus, but also influenced by the information density of individuals. We also find that the critical threshold is independent of the information generation probability, and the loss of the information will lead to a decrease. Finally, to verify the theoretical derivations, we apply it on both artificial network and real social network. The experimental results show that the simulations perfectly coincide with theoretical results, which verified the effectiveness of our model.

Flammulina velutipes is the fourth largest edible fungus in China with high nutritional value. In this paper, ultrahigh-performance liquid chromatography tandem hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-Orbitrap MS) was used to identify the secondary metabolites of F. velutipes. The metabolites were identified by comparing the retention time, accurate molecular weight, and MS2 data with standard databases of mzVault and mzCloud (compound: 17,000+) and BGI high-resolution accurate mass plant metabolome database (plant metabolite: 2500+). Finally, 26 secondary metabolites were preliminarily identified, including flavonoids, phenylpropanoids, organic acids, and steroids.

Aims Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model. Methods The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA). Results PARP-1 expression level significantly increased in the cartilage of the established OA rat model. sh-PARP-1 treatment suppressed PARP-1 levels, decreased the Δ Force (the difference between the weight on ipsilateral limb and contralateral limb) and the knee joint width, inhibited cartilage matrix catabolic enzymes, and ameliorated OA cartilage degradation and attenuated inflammatory response. Conclusion PARP-1 inhibition attenuates OA cartilage inflammatory response in the OA rat model. Cite this article: Bone Joint Res 2021;10(7):401–410.

This study aimed to perform a cluster analysis of symptoms linked withFrom 15 April to 16 May 2018, a cross-sectional study was conducted, and patients attending sexually transmitted infections (STI) related clinics were recruited from 22 medical institutions in six districts of Shenzhen city.A structured questionnaire was used to collect social-demographic information as well as STI symptoms, and urine samples were collected for nucleic acid detection. Cluster analysis and logistic regression were applied.Among 8,207 participants, the prevalence of CT and NG infection was 9.04% (742/8,207) and 2.36% (194/8,207), respectively. Among male outpatients, four clusters with distinct symptomatic patterns were identified. Unmarried, having casual sexual partners in the past 6 months, cluster 2 (OR = 6.70, 95% CI = 3.36-13.35) and cluster 4 (OR = 24.53, 95% CI = 12.96-46.44) were risk factors associated with NG infection. Unmarried, cluster 2 (OR = 2.54, 95% CI = 1.83-3.53) and cluster 4 (OR = 3.31, 95% CI = 2.37-4.61) were risk factors associated with CT infection. Among female outpatients, five clusters with distinct symptomatic patterns were identified. Aged 24 years or below and cluster 3 (OR = 3.68, 95% CI = 1.61-8.39) were risk factors associated with NG infection. Aged 24 years or below, unmarried, having a high school/secondary technical school education, and having junior high school or below education were risk factors associated with CT infection.The cluster of symptoms integrated into risk assessment for CT and NG infections suggests a new strategy of symptomatic management. Healthcare providers in STI clinics and resource-limited places may use this strategy to identify more potential patients and deliver adequate, acceptable, and equitable STI care for outpatients with a high risk of STI.

SUMMARYSystematic understanding of immune dynamics across the entire human lifespan at single-cell resolution is currently lacking. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor (TCR)/B cell receptor (BCR) sequencing (scTCR/BCR-seq) on over 380,000 peripheral blood mononuclear cells collected from 45 healthy participants aged 0 to over 90 years. We revealed that the functions of T cell subsets were most susceptible to senescence among all PBMCs, featured by increased NF-κB signaling and IFN-γ responses pathways, while reduced telomere maintenance and energy metabolism. We subsequently explored the rewiring of cell-cell interactions among different immune cells across the lifespan and revealed the major alteration of immune checkpoints in T cells within the cellular interaction networks. By combined analysis of scRNA-seq and scTCR-seq, we revealed that 1) GNLY+CD8 Effector T cells exhibited a high clonal expansion with distinct functional signatures in children and the elderly; 2) Naïve CD4+T and naïve CD8+T cells displayed different aging patterns in both transcriptomes and immune repertoires; and 3) CD8+MAIT cells showed a higher cell abundance and clonal diversity in adolescents. Furthermore, we identified a unique cytotoxic B cell subset enriched in children by scRNA-seq and scBCR-seq analysis and experimental validations. In summary, our work provided valuable insights and rich resources for understanding the development and aging of the human immune system across the lifespan.

Hericium erinaceus is a precious edible and medicinal fungus with high nutritional value. It has many functions, such as enhancing immunity, antitumor antioxidation, antihyperglycemic, antihyperlipidemic, and protecting gastric mucosa. However, there are few researches about the H. erinaceus compounds. In this paper, ultraperformance liquid chromatography tandem high-resolution mass spectrometry (UPLC-Q-exactive-MS/MS) was used to isolate and identify the compounds in H. erinaceus. 102 compounds were identified in H. erinaceus by comparing with standard databases such as MZVault, MZCloud, and BGI Library (self-built standard Library by BGI Co., Ltd), including flavonoids, terpenoids, phenolic acids, phenylpropanoids, steroids, organic acids, and amino acids.

IL-17–secreting Th17 cells play an important role in the pathogenesis of various inflammatory and autoimmune diseases. IL-17–targeted biologics and small molecules are becoming promising treatments for these diseases. In this study, we report that SZB120, a derivative of the natural compound 3-acetyl-β-boswellic acid, inhibits murine Th17 cell differentiation by interacting with the α-subunit of eukaryotic initiation factor 2 (eIF2α). We showed that SZB120 directly interacts with eIF2α and contributes to serine 51 phosphorylation of eIF2α. The suppressive effect of SZB120 on Th17 cell differentiation was reversed by GSK2606414, an inhibitor of eIF2α phosphokinase. Phosphorylation of eIF2α induced by SZB120 decreased the protein expression of IκBζ, which is important for Th17 cell differentiation. Notably, interaction with eIF2α by SZB120 also impaired glucose uptake and glycolysis in T cells. In vivo, SZB120 treatment of C57BL/6 mice significantly attenuated IL-17/Th17–mediated autoimmune disease. Our study indicates that SZB120 is a promising drug candidate for IL-17/Th17–mediated inflammatory diseases.

Fungi play an important role in mediating soil functioning and plant nutrients absorption. Although nitrogen (N) addition and reduced precipitation can affect fungal community composition, the resp...

Endometriosis is a chronic disorder characterized by the implantation of endometrial glands and stroma outside the uterus. However, the pathogenesis of endometriosis is still unclear. To date, there is no fully effective treatment without trauma because of various side effects. Recent data suggest that ferroptosis is a novel recognized form of nonapoptosis-regulated cell death characterized by iron-dependent and lethal lipid peroxidation accumulation, showing great promise in the treatment of many diseases. In the present study, we verified that erastin induced ferroptosis in ectopic endometrial stromal cells (EESCs). Furthermore, we found that the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was decreased during erastin-induced ferroptosis. Knockdown of MALAT1 significantly aggravated the inhibition of cell viability and increased intracellular iron, Liperfluo, and MDA levels in EESCs upon erastin treatment. Mechanistically, we demonstrated that MALAT1 served as a competing endogenous RNA of miR-145-5p to regulate the expression of MUC1, a suppressor of ferroptosis. MALAT1 knockdown-mediated ferroptotic cell death and MUC1 downregulation could be abrogated by inhibition of miR-145-5p. In addition, miR-145-5p inhibition-mediated ferroptotic cell death could be abolished by MUC1 knockdown. Furthermore, erastin-induced ferroptosis shrunk endometriotic lesions via the MALAT1/miR-145-5p/MUC1 axis in vivo. Taken together, our data indicate that knockdown of MALAT1 facilitates ferroptosis upon erastin treatment via miR-145-5p/MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis.

Background Neonatal hyperbilirubinemia is one of the leading causes of neonatal readmission—especially severe hyperbilirubinemia and its complications—and it influences disease burden as well as neonatal and maternal health. Smartphones have been shown to have satisfactory accuracy in screening neonatal bilirubin levels, but the impact of this technology on neonatal health care service and maternal health outcomes is still unknown. Objective The aim of this study was to evaluate the impact of a smartphone-based out-of-hospital neonatal jaundice screening program on neonatal readmission rates for jaundice and related maternal anxiety. Methods This was a 2-arm, unblinded, randomized controlled trial with 30 days of intervention and follow-up periods. From August 2019 to August 2020, healthy mother-infant dyads were recruited on-site from 3 public hospitals in Hainan, China. Intervention group mothers used the smartphone app to routinely monitor neonatal jaundice at home under the web-based guidance of pediatricians. Control group participants received routine care. The primary study outcome was the neonatal readmission rate due to jaundice within 30 days of the first hospital discharge. The secondary outcome was the maternal anxiety score associated with neonatal jaundice. The data were collected through a self-assessed questionnaire. All participants were included in the analysis (intention-to-treat). Results In this study, 1424 mother-infant dyads were recruited, comprising 1424 mothers and 1424 newborns. The median age of the mothers was 29 (IQR 26-32) years, and there were 714 (50.1%) male neonates. These mother-infant dyads were randomly assigned to the intervention group and the control group, with 712 dyads in each group; only 1187 of these dyads completed the follow-up. We found that the adjusted 30-day neonatal readmission rate due to jaundice reduced by 10.5% (71/605, 11.7% vs 141/582, 24.2%; 95% CI 5%-15.9%; odds ratio 0.4, 95% CI 0.3-0.5; P Conclusions Our study shows that the smartphone-based out-of-hospital screening method for neonatal hyperbilirubinemia decreased the neonatal readmission rate within 30 days from the first discharge and improved maternal mental health to some degree, thus demonstrating the usefulness of this screening app for follow-up in pediatric care. Trial Registration China Clinical Trial Registration Center, ChiCTR2100049567; http://www.chictr.org.cn/showproj.aspx?proj=64245

Recent evidence has revealed that small polypeptides (containing fewer than 100 amino acids) can be translated from noncoding RNAs (ncRNAs), which are usually defined as RNA molecules that do not encode proteins. However, studies on functional products translated from primary transcripts of microRNA (pri‐miRNA) are quite limited. Here, we describe a peptide termed miPEP31 that is encoded by pri‐miRNA‐31. miPEP31 is highly expressed in Foxp3(+) regulatory T cells (T(regs)) and significantly promotes the differentiation of T(regs) without affecting their inhibitory ability. Our results show that miPEP31 is a cell‐penetrating peptide both in vitro and in vivo. miPEP31 downregulates miR‐31 expression, enhances peripheral T(reg) induction, and dramatically suppresses experimental autoimmune encephalomyelitis. Mechanistically, we show that miPEP31 acts as a transcriptional repressor inhibiting the expression of miRNA‐31, a negative regulator of T(regs). Our results reveal an indispensable role of miPEP31 in maintaining immune homeostasis by promoting T(reg) differentiation and also present a potential therapeutic peptide for modulating miRNA expression and treating autoimmune diseases.

With the development of quantum theory, traditional encryption algorithms are facing enormous challenges. Once quantum computers are available, existing encryption systems will no longer be secure. The lattice cipher is proven by theory to be a new type of encryption scheme, which can resist quantum algorithm. It has the property of fast computing speed and small space occupation, hence, it has become a hot issue in today??s research. The identity-based encryption scheme can improve the utilization of storage space and facilitate user public key management. Consequently, this paper based on the hard problem of learning with errors (LWE), constructs an identity-based matrix encryption scheme at first, then applies the improved key switching technology to reduce the dimension of homomorphic ciphertext to normal, and uses the mode conversion technique to reduce noise, realizing matrix homo-morphic operation, and getting an identity-based matrix (level) fully homomorphic encryption scheme. The scheme uses matrices as the storage structure, which has greatly improved the processing capability compared to other single-bit schemes. The scheme not only satisfies the addition and Hadamard product of the matrix, but also supports matrix dot multiplication. The experimental results show that compared with other methods, the improved key switching technology in this paper inputs less noise. Through the difficulty of the LWE problem, it is proven that the scheme satisfies IND-sID-CPA (indistinguishability-selective identity-chosen plaintext attack).

Background Systemic chemotherapy is often the last resort of advanced cutaneous T-cell lymphoma (CTCL). Tumor recurrence and adverse effects of systemic chemotherapy are the main limitations. Objective We aim to investigate the metabolic alterations in tumor cells after CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) chemotherapy. Methods and results In advanced CTCL, CHOP chemotherapy has no survival benefit and the duration of response is significantly inferior to other canonical treatments. HIF-1α is significantly elevated in lesions of advanced MF patients as well as tumor cell line Hut78 and tumor xenograft mice model. CHOP therapy also increased glycolytic activities in a HIF-1α-dependent manner. In CTCL xenograft tumor mice model, lesional cells showed a significant increase in IL-17F after chemotherapy, shifting toward a Th17 phenotype, which process is also regulated by HIF-1α. Echinomycin, HIF-1α inhibitor, was co-administered in xenograft tumor mouse models with CHOP and showed a significant reduction in tumor growth. Conclusion CHOP chemotherapy promotes glycolysis and IL-17 pathways in a HIF-1α-dependent fashion. Furthermore, HIF-1α blockade is promising as an accompanying agent in systemic chemotherapy for patients with advanced CTCL.

We conducted a field experiment with four levels of simulated nitrogen (N) deposition (0, 2.5, 5, and 7.5 g N m−2 yr−1, respectively) to investigate the response of litter decomposition of Pinus koraiensis (PK), Tilia amurensis (TA), and their mixture to N deposition during winter and growing seasons. Results showed that N addition significantly increased the mass loss of PK litter and significantly decreased the mass loss of TA litter throughout the 2 yr decomposition processes, which indicated that the different responses in the decomposition of different litters to N addition can be species specific, potentially attributed to different litter chemistry. The faster decomposition of PK litter with N addition occurred mainly in the winter, whereas the slower decomposition of TA litter with N addition occurred during the growing season. Moreover, N addition had a positive effect on the release of phosphorus, magnesium, and manganese for PK litter and had a negative effect on the release of carbon, iron, and lignin for TA litter. Decomposition and nutrient release from mixed litter with N addition showed a non-additive effect. The mass loss from litter in the first winter and over the entire study correlated positively with the initial concentration of cellulose, lignin, and certain nutrients in the litter, demonstrating the potential influence of different tissue chemistries.

NOx, as the main air pollutant in the atmosphere, its elimination has attracted wide attention. Several technologies for eliminating NOx have been investigated by some researchers, and the selective catalytic reduction (SCR) of NOx with hydrocarbons has been proven to be an efficacious denitrification technology. Studies have suggested that excellent catalytic performances at low temperatures can be obtained over copper-based zeolite catalysts for HC-SCR. This review summarized the development of copper-based zeolite catalysts for HC-SCR and elaborated the synthesis methods, low-temperature catalytic performance, and reaction mechanism of the catalysts with different compositions and structures. The purpose of this review is to highlight (1) the structure–activity relationship of copper-based zeolite catalysts; (2) the main factors affecting the low-temperature catalytic activity; (3) the HC-SCR reaction mechanism of the copper-based zeolite catalysts; and (4) the design strategies for the copper-based zeolite catalysts with excellent low-temperature catalytic activity for HC-SCR.

Currently there is tremendous interest in the discovery of natural polysaccharide immunomodulators for treating immune-related diseases. Herein, the immunomodulatory activities of a polysaccharide fraction isolated from blackberry seeds (BSP-2) were examined in RAW264.7 cells. The results revealed that BSP-2 at 37.5–300 µg/mL could significantly enhance the phagocytic activity of RAW264.7 cells and their ability to release NO, TNF-α and IL-6 cytokines. BSP-2 could significantly up-regulate the mRNA expression of iNOS, TNF-α and IL-6, as well as the phosphorylation of p65, p38, ERK and JNK proteins. The mechanisms underlying the immunomodulatory actions of BSP-2 likely involve the activation of the NF-κB and MAPK signaling pathways and up-regulation of the phosphorylation of key proteins involved in these pathways. These findings suggest that BSP-2 could be applied as a polysaccharide immunotherapeutic adjuvant with the effective dose as low as 70 µg/mL (BSP-2 may be cytotoxic at levels > 600 μg/mL). Highlights Immunostimulatory potential of a blackberry seed polysaccharide (BSP-2) was examined. BSP-2 at 37.5–300 µg/mL could enhance the phagocytic activity of RAW264.7 cells. BSP-2 could significantly up-regulate the mRNA expression of iNOS, TNF-α and IL-6. BSP-2 up-regulated the phosphorylation of p65, p38, ERK and JNK proteins. Immunostimulatory BSP-2 acted via activating the NF-κB and MAPK signalling pathways.

Isolated Rh atoms are supported on hydrophobic dB-ZSM-5. Single-atom Rh on dB-ZSM-5 is characterized with Ac-HAADF/STEM and CO adsorption FTIR. Direct conversion of methane to oxygenates is carried out in an autoclave in water charged with CH4, O2 and CO at 150 °C. Hydrophobic Rh-dB-ZSM-5 is compared with hydrophilic Rh-ZSM-5 (Si/Al = 15) for its catalytic performance. Rh-dB-ZSM-5 catalyst exhibits higher CH3OH selectivity and lower CH3COOH and CO2 selectivity. The catalytic activity of Rh-dB-ZSM-5 is much higher than the activity of Rh-ZSM-5 when the reaction is carried out under low pressure.