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Abstract Photon management strategies are crucial to improve the efficiency of perovskite thin film (PTF) solar cell. In this work, a nano-cone (NC) based 2D photonic nanostructure is designed and simulated aiming at achieve superior light trapping performance by introducing strong light scattering and interferences within perovskite active layer. Compared to the planar PTF solar cell, the NC nanostructured device with 45 degrees half apex angle obtains highest short-circuit current density, which improved over 20% from 15.00 mA/cm2 to 18.09 mA/cm2. This work offers an alternative design towards effective light trapping performance using 2D photonic nanostructure for PTF solar cell and could potentially be adopted as the nano-structuring strategy for the future perovskite solar cell industry.

Abstract TnpBs encoded by the IS200/IS605 family transposon are among the most abundant prokaryotic proteins from which type V CRISPR-Cas nucleases may have evolved. Since bacterial TnpBs can be programmed for RNA-guided dsDNA cleavage in the presence of a transposon-adjacent motif (TAM), these nucleases hold immense promise for genome editing. However, the activity and targeting specificity of TnpB in homology-directed gene editing remain unknown. Here we report that a thermophilic archaeal TnpB enables efficient gene editing in the natural host. Interestingly, the TnpB has different TAM requirements for eliciting cell death and for facilitating gene editing. By systematically characterizing TAM variants, we reveal that the TnpB recognizes a broad range of TAM sequences for gene editing including those that do not elicit apparent cell death. Importantly, TnpB shows a very high targeting specificity on targets flanked by a weak TAM. Taking advantage of this feature, we successfully leverage TnpB for efficient single-nucleotide editing with templated repair. The use of different weak TAM sequences not only facilitates more flexible gene editing with increased cell survival, but also greatly expands targeting scopes, and this strategy is probably applicable to diverse CRISPR-Cas systems.

In this study, we investigated the effects of major royal jelly proteins (MRJPs) on the estrogen, gut microbiota, and immunological responses in mice. Mice given 250 or 500 mg/kg, not 125 mg/kg of MRJPs, enhanced the proliferation of splenocytes in response to mitogens. The splenocytes and mesenteric lymphocytes activated by T-cell mitogens (ConA and anti-CD3/CD28 antibodies) released high levels of IL-2 but low levels of IFN-γ and IL-17A. The release of IL-4 was unaffected by MRJPs. Additionally, splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1β and IL-6, two pro-inflammatory cytokines. The production of IL-1β, IL-6, and IFN-γ was negatively associated with estrogen levels, which were higher in the MRJP-treated animals than in the control group. Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice. Additionally, the LEfSe analysis identified biomarkers in the MRJP-treated mice, including Prevotella, Bacillales, Enterobacteriales, Gammaproteobacteria, Candidatus_Arthromitus, and Shigella. Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations (microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

Abstract Background Medical university students are confronted with unprecedented uncertainty and stress compared with their peers. Research has explored the effect of intolerance of uncertainty on perceived stress, but little attention was paid to investigate the mediating mechanisms behind this relationship, especially among medical university students. The aim of this study was to examine whether psychological resilience and neuroticism played a mediating role between medical university students’ intolerance of uncertainty and perceived stress. Methods A total of 717 medical university students from Chongqing in Southwest China were recruited to participate in our study and completed demographic information, Intolerance of Uncertainty Scale Short Version (IUS-12), Chinese Version of Perceived Stress Scale (CPSS), Connor-Davidson Resilience Scale-10 (CD-RISC-10) and Eysenck Personality Questionnaire (EPQ). Results (1) Significant correlations between intolerance of uncertainty, perceived stress, psychological resilience and neuroticism were found. (2) Intolerance of uncertainty affected medical university students’ perceived stress via three paths: the mediating effect of psychological resilience, the mediating effect of neuroticism, and the chain mediating effect of both psychological resilience and neuroticism. Conclusions Intolerance of uncertainty could directly affect the perceived stress of medical university students, and also affected perceived stress through the mediating roles of psychological resilience and neuroticism, as well as through the chain mediating role of these two variables.

Microneedle, as a novel drug delivery system, has attracted widespread attention due to its non-invasiveness, painless and simple administration, controllable drug delivery, and diverse cargo loading capacity. Although microneedles are initially designed to penetrate stratum corneum of skin for transdermal drug delivery, they, recently, have been used to promote wound healing and regeneration of diverse tissues and organs and the results are promising. Despite there are reviews about microneedles, few of them focus on wound healing and tissue regeneration. Here, we review the recent advances of microneedles in this field. We first give an overview of microneedle system in terms of its potential cargos (e.g., small molecules, macromolecules, nucleic acids, nanoparticles, extracellular vesicle, cells), structural designs (e.g., multidrug structures, adhesive structures), material selection, and drug release mechanisms. Then we briefly summarize different microneedle fabrication methods, including their advantages and limitations. We finally summarize the recent progress of microneedle-assisted wound healing and tissue regeneration (e.g., skin, cardiac, bone, tendon, ocular, vascular, oral, hair, spinal cord, and uterine tissues). We expect that our article would serve as a guideline for readers to design their microneedle systems according to different applications, including material selection, drug selection, and structure design, for achieving better healing and regeneration efficacy.

With the rapid development and construction of urban subways, various risks associated with human health and wellbeing within subway microenvironments have seriously increased. However, only a few intelligent systems have been validated as suitable for facilitating the management of subway environments. Field tests can be time-consuming and inefficient, and questionnaires often lack true intuitiveness for participants. Therefore, to enhance subway environment management, this study proposed intelligent systems that integrate building information modeling (BIM) and virtual reality (VR) for managing health risks in urban subway microenvironments. The systems were developed using Revit 2021, Navisworks 2020, Unity 2019, MYSQL 8.0, and Visual Studio 2019. Additionally, they were applied in scenarios for environmental assessment and passenger coping capability enhancement, differentiated into an expert visual-based health risk assessment system and a gamified simulation system for passenger risk prevention. The feasibility of the approach was validated with the case of Xinzhuang subway station of Line 3 in Nanjing, China. The findings revealed that the assessment system enabled experts to have a better and straight understanding of subway microenvironmental health risks and the gamification simulation system significantly enhanced the passengers’ coping capacity. The integration of BIM and VR, with its design features such as visibility, optimization, and simulation, compensated for BIM’s lack of providing an immersive experience for systems. The intelligent systems introduced in this study present novel models for environmental assessment and passenger training, catering to both subway operators and researchers. The innovative systems serve as a cornerstone in guaranteeing the health and safety of public transportation operations.

The imagery of wine and tea is important in classical and modern Chinese poetry, with an intricate relationship between the two especially evident in the work of Taixu 太虛 (1890–1947), a prominent poet–monk in 20th-century China. Taixu’s attitude toward wine—a drink that is deeply rooted in Chinese culture—evolves significantly over time, from initial approval to eventual condemnation due to its detrimental effects on both personal health and society. Nevertheless, it continues to feature prominently in his poetry. The same is true of tea, which Taixu often uses to evoke either Buddhist study or his own healthy lifestyle. This article explores this and other complex meanings in Taixu’s poems, such as his association of wine with knights and tea with hermits. It also discusses how he achieves a delicate balance between the two beverages, sometimes employing both types of imagery in a single poem—a literary innovation that helped to establish his reputation as a central figure in modern Chinese poetry.

Abstract Background Case-based learning (CBL) has been found to be effective for many subjects, but there is currently a lack of evidence regarding its utility in psychology education. The present study investigated whether CBL pedagogy can improve students’ academic performance in psychology courses compared to the traditional teaching methods. Methods A systematic review and meta-analysis were conducted to investigate the effectiveness of CBL in psychology teaching. Databases including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), the VIP database, and Wanfang data were searched to find eligible randomized controlled trials. Pooled effect estimates were calculated using Hedges’ g under the random effects model, and a subgroup analysis was carried to investigate the heterogeneity among studies. Results Fifteen studies with 2172 participants, 1086 in the CBL group and 1086 in the traditional lecture-based teaching group, were included in the meta-analysis. Students in the CBL group scored significantly higher on exams than those in the lecture-based group [Hedges’ g = 0.68, 95%CI (0.49, 0.88), p

Objective To evaluate the safety and efficacy of the collection of peripheral blood stem cells (PBSCs) in pediatric patients with thalassemia major (TM) weighing 20 kg or less. Methods PBSCs collection data of 170 pediatric patients with TM weighing 20 kg or less from January 2013 to December 2020 in our center were reviewed. Safety was assessed by the occurrence of adverse events during apheresis procedures, and efficacy was evaluated by the number of CD34+ cells collected. Results A total of 171 PBSCs procedures were performed on 170 patients with TM weighing 20 kg or less, with a median age of (4.98±1.53) years and a median weight of (17.30±2.18) kg. The probability of collecting at least 1×106 CD34+ cells/kg during a single course of apheresis was 99.41% (169/170), with a median (5.88±4.23) ×106 CD34+ cells collected per kg of weight of the recipient. A minimum pre-apheresis hemoglobin (Hb) of 60 g/L in patients with TM weighing 20 kg or less was safe and feasible. The most common adverse event of G-CSF mobilization in TM patients is bone pain, with the incidence of 7.65% (13/170), which was higher than that of healthy children donors in our center. The most common adverse events during the collection were pain at the puncture site of the femoral vein (6.47%, 11/170) and low pressure of the fluid (2.92%, 5/170). And no serious complications related to PBSCs mobilization, central venous catheter(CVC)placement or the apheresis procedure occurred. Conclusion PBSCs collection by COM.TEC blood cell separator in children weighing 20 kg or less is safe and efficacious.

Abstract Background Postoperative pulmonary insufficiency (PPI) is an important contributor to morbidity and mortality after thoracic surgery. Lung ultrasound is a reliable tool for assessing respiratory function. We sought to determine the clinical value of the early lung ultrasound B-line score for predicting changes in pulmonary function after thoracic surgery. Methods Eighty-nine patients undergoing elective lung surgery were included in this study. The B-line score was determined 30 min after removal of the endotracheal tube, and the PaO2/FiO2 ratio was recorded 30 min after extubation and on the third postoperative day. Patients were divided into normal (PaO2/FiO2 ≥ 300) and PPI (PaO2/FiO2

Abstract Background Inflammatory bowel disease (IBD) is a non‐specific chronic inflammatory disease of the intestine. In addition to genetic susceptibility, environmental factors and dysregulated host immunity, the gut microbiota is implicated in the pathogenesis of Crohn's disease (CD) or ulcerative colitis (UC), the two primary types of IBD. The P2X4 receptor has been demonstrated to have a crucial role in preventing infection, inflammation, and organ damage. However, it remains unclear whether the P2X4 receptor affects IBD and the underlying mechanisms. Methods Colitis was induced in mice administrated with dextran sodium sulphate (DSS). 16S rDNA sequencing was used to analyze the gut microbiota in knockout and wild‐type mice. Clinical and histopathological parameters were monitored throughout the disease progression. Results Gene Expression Omnibus analysis showed the downregulation of P2RX4 (P2rx4) expression in colonic tissues from patients or mice with IBD. However, its expression at the protein levels was upregulated on day 4 or 6 and then downregulated on day 7 in C57BL/6 mice treated with DSS. Gene ablation of P2rx4 aggravated DSS‐induced colitis accompanying gut microbiota dysbiosis in mice. Moreover, P2X4 receptor‐positive modulator ivermectin alleviated colitis and corrected dysregulated microbiota in wild‐type C57BL/6 mice. Further antibiotic‐treated gut microbiota depletion, cohousing experiment, and fecal microbiota transplantation proved that gut microbiota dysbiosis was associated with the aggravation of colitis in the mouse model initiated by P2rx4. Conclusions Our findings elaborate on an unrevealed etiopathophysiological mechanism by which microbiota dysbiosis induced by the P2X4 receptor influences the development of colitis, indicating that the P2X4 receptor represents a promising target for treating patients with CD and UC.

Summary Engineered Saccharomyces cerevisiae strains are good cell factories, and developing additional genetic manipulation tools will accelerate construction of metabolically engineered strains. Highly repetitive rDNA sequence is one of two main sites typically used for multicopy integration of genes. Here, we developed a simple and high‐efficiency strategy for rDNA‐mediated multicopy gene integration based on the dynamic balance of rDNA in S. cerevisiae. rDNA copy number was decreased by pre‐treatment with hydroxyurea (HU). Then, heterologous genes were integrated into the rDNA sequence. The copy number of the integrated heterologous genes increased along with restoration of the copy number of rDNA. Our results demonstrated that HU pre‐treatment doubled the number of integrated gene copies; moreover, compared with removing HU stress during transformation, removing HU stress after selection of transformants had a higher probability of resulting in transformants with high‐copy integrated genes. Finally, we integrated 18.0 copies of the xylose isomerase gene into the S. cerevisiae genome in a single step. This novel rDNA‐mediated multicopy genome integration strategy provides a convenient and efficient tool for further metabolic engineering of S. cerevisiae.

Ivermectin has been proposed as a potential anti-inflammatory drug in addition to its antiparasitic activity. Here we investigated the potential role of ivermectin in the pathogenesis of acute lung injury (ALI) using the lipopolysaccharide (LPS)- or bleomycin (BLM)-induced mice models. Male C57BL/6 mice were given ivermectin orally every day for the remainder of the experiment at doses of 1 or 2 mg/kg after 24 h of LPS or BLM treatment. Ivermectin reversed severe lung injury caused by LPS or BLM challenge, including mortality, changes in diffuse ground-glass and consolidation shadows on lung CT imaging, lung histopathological scores, lung wet/dry ratio, and protein content in the bronchoalveolar lavage fluid (BALF). Furthermore, ivermectin also reduced total lung BALF inflammatory cells, infiltrating neutrophils, myeloperoxidase activity, and plasma TNF-α and IL-6 levels in mice treated with LPS or BLM. Finally, the mechanism study showed that LPS or BLM administration increased JNK, Erk1/2, and p38 MAPK phosphorylation while decreasing IκBα expression, an inhibitor of NF-κB. However, ivermectin increased IκBα expression but blocked elevated phosphorylated JNK and p38 MAPK, not Erk1/2, in both ALI mice. These findings suggested that ivermectin may alleviate ALI caused by LPS or BLM in mice, partly via lowering the inflammatory response, which is mediated at least by the inhibition of MAPK and NF-κB signaling. Collectively, ivermectin might be used to treat acute lung injury/acute respiratory distress syndrome.

This study explored the profibrotic impact of high glucose in the lung and potential mechanisms using latent TGF-β1-induced human epithelial cell pulmonary fibrosis and bleomycin (BLM)-induced pulmonary fibrosis models. Results demonstrated that high glucose administration induced epithelial–mesenchymal transition (EMT) in human epithelial cells in a dose-dependent manner via activating latent TGF-β1, followed by increased expression of mesenchymal-related proteins and decreased expression of epithelial marker protein E-cadherin. Further mechanism analysis showed that administration of high glucose dose-dependently promoted total and mitochondrial reactive oxygen species (ROS) accumulation in human epithelial cells, which promoted latent TGF-β1 activation. However, N-acetyl-L-cysteine, a ROS eliminator, inhibited such effects. An in vivo feed study found that mice given a high-glucose diet had more seriously pathological characteristics of pulmonary fibrosis in BLM-treated mice, including increasing infiltrated inflammatory cells, collagen I deposition, and the expression of mesenchymal-related proteins while decreasing the expression of the epithelial marker E-cadherin. In addition, high glucose intake further increased TGF-β1 concentration and upregulated p-Smad2/3 and snail in lung tissues from BLM-treated mice when compared to BLM-treated mice. Finally, supplementation with high glucose further increased the production of lipid peroxidation metabolite malondialdehyde and decreased superoxide dismutase activity in BLM-treated mice. Collectively, these findings illustrate that high glucose supplementation activates a form of latent TGF-β1 by promoting ROS accumulation and ultimately exacerbates the development of pulmonary fibrosis.

This study numerically investigated the heat transfer characteristics of the supercritical CO2 under the non-uniform cooling condition. The non-uniformity of heat flux distribution on a typical air-cooled exchanger is estimated at first and the heat transfer performances of supercritical CO2 under uniform and non-uniform cooling conditions are compared. The results demonstrated that the heat flux of the finned tube exhibited a significantly uneven distribution along the circumferential tube wall, and the unevenness increased with an increase in the wind speed. A clear distinction can be observed between uniform cooling and non-uniform cooling of supercritical CO2. Different from the non-uniformly heated CO2, when the bulk temperature is much higher than the pseudocritical point, the average heat transfer coefficient of non-uniformly cooled supercritical CO2 was 6.84% higher than that of the uniformly cooled supercritical CO2 and the situation is reversed when the bulk temperature was close to the pseudocritical point. The difference between non-uniform cooling and uniform cooling increased with an increase in the unevenness of the heat flux and fluid mass flux. The non-linear change of thermophysical properties and the buoyancy effect of CO2 near the pseudocritical point are the main reasons for the difference between uniform cooling and non-uniform cooling.

Taixu 太虛 (1890–1947), a prominent figure in modern Chinese Buddhism, produced a voluminous collection of poetry abounding with diverse classical Chinese images. Notably, the “lamp and candle” (dengzhu 燈燭) holds great significance, reflecting Taixu’s personal affinity with this imagery and an intimate connection to classical Chinese poetry. Acting as a potent Buddhist metaphor, it encapsulates multifaceted sentiments while also intertwining with other evocative images, such as the boat, the moon, and falling leaves. Symbolizing Taixu’s unwavering spirit, it represents his profound dedication to his craft. This article explores Taixu’s literary achievements as a poet by focusing on his adept utilization of “lamp and candle” imagery, complementing the study of his multifaceted and intricate identities. This detailed examination offers novel insights into Chinese literature and Buddhist studies, highlighting the interplay between spiritual practice and artistic expression.

As the global climate continues to change, lowering carbon emissions of public buildings (CEPB) is essential for reducing carbon emissions from the construction sector. Exploring the current status of the field is crucial to improving the effort to reduce CEPB. CiteSpace and VOSviewer are used in this research to visualize the literature on CEPB from the Web of Science Core Collection from 2002 to 2022, including an overview, collaborations, and keywords, as well as references. The paper then analyzes and reviews the research processes of CEPB in conjunction with the visualization results and the collation of information from the literature. The results show that the current research hotspots include (1) theoretical research and simulation modeling, (2) energy systems, (3) materials, (4) public building retrofitting, (5) the main factors that contribute to the reduction in CEPB. Architectural features and structures and digital technology are the frontiers of research in the field of CEPB. In general, there is still sufficient space to develop in the field. These findings intuitively encapsulate the valuable information and inherent value of a significant body of literature, which can help researchers quickly understand the field and provide some references.

In the central nervous system (CNS), the myelin sheath ensures efficient interconnection between neurons and contributes to the regulation of the proper function of neuronal networks. The maintenance of myelin and the well-organized subtle process of myelin plasticity requires cooperation among myelin-forming cells, glial cells, and neural networks. The process of cooperation is fragile, and the balance is highly susceptible to disruption by microenvironment influences. Reactive microglia play a critical and complicated role in the demyelination and remyelination process. Recent studies have shown that the voltage-gated proton channel Hv1 is selectively expressed in microglia in CNS, which regulates intracellular pH and is involved in the production of reactive oxygen species, underlying multifaceted roles in maintaining microglia function. This paper begins by examining the molecular mechanisms of demyelination and emphasizes the crucial role of the microenvironment in demyelination. It focuses specifically on the role of Hv1 in myelin repair and its therapeutic potential in CNS demyelinating diseases. [ABSTRACT FROM AUTHOR]

Abstract Long non-coding RNA growth arrest specific transcript 5 (GAS5) has been found to be implicated in the pathogenesis of central nervous diseases and to be a contributor to hypoxic brain injury. However, the roles and molecular mechanisms of GAS5 in spinal cord injury (SCI) have not thoroughly investigated. Here, we reported that GAS5 knockdown improved rat locomotor function and alleviated pathological damage of spinal cord tissues by reducing oxidative stress, caspase-3 activity and vav guanine nucleotide exchange factor 1 (VAV1) expression in SCI rat models. GAS5 knockdown inhibited the increase of malondialdehyde (MDA) level and cell apoptotic rate induced by oxygen–glucose deprivation (OGD) and weakened the inhibitory effects of OGD on superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and cell viability in RN-Sc cells, suggesting that GAS5 loss mitigated OGD-triggered oxidative stress and cell injury in RN-Sc cells. Molecular mechanism explorations revealed that GAS5 recruited CUGBP, Elav-like family member 2 (CELF2) to the coding region of VAV1 mRNA, resulting in the increase of VAV1 mRNA stability and expression levels. VAV1 knockdown weakened OGD-induced oxidative stress and cell injury in RN-Sc cells. VAV1 loss alleviated GAS5-induced oxidative stress and cell injury in OGD-treated RN-Sc cells. As a conclusion, our findings suggested that GAS5 aggravated SCI by increasing VAV1 expression via binding with CELF2, deepening our understanding on function and molecular basis of GAS5 in SCI.

AbstractBackground Preeclampsia (PE), one of hypertension-related disorders of pregnancy, is a common cause of maternal death worldwide. This study aimed to identify a circRNA-miRNA-mRNA-associated ceRNA network and related pathways in PE.Material and methods We downloaded 3 microarray datasets from the Gene Expression Omnibus database, obtained 163 differentially expressed circRNAs (dif-circRNAs) (61 upregulated and 102 downregulated), 39 differentially expressed microRNAs (dif-miRNAs) (22 upregulated and 17 downregulated), and 271 differentially expressed mRNAs (dif-mRNAs) (168 upregulated and 103 downregulated) from placenta tissues of PE. Functional enrichment analysis and protein-protein interaction (PPI) network with module analysis of dif-mRNAs were performed. The regulatory relationship between dif-miRNAs and dif-mRNAs/circRNAs was predicted via related databases. A circRNA-miRNA-mRNA regulatory network was constructed.Results A total of 53 pairs were obtained, including 13 circRNAs (10 upregulated and 3 downregulated), 9 miRNAs (3 upregulated and 6 downregulated) and 31 mRNAs (22 upregulated and 9 downregulated). GNB5 and IL2RB were obtained. KEGG enrichment analysis showed that both of them were closely related with the PI3K-Akt signalling pathway. Therefore, ceRNAs might affect the PI3K-Akt signalling pathway via the upregulation of GNB5 by binding to miR-1248 in PE. Meanwhile, hsa_circ_0052661 might upregulate IL2RB by binding miR-4303 to play a role in PE in the same way.Conclusion GNB5 and IL2RB might be key genes involved in the PI3K-Akt signalling pathway in PE, and hsa_circ_0087208, hsa_circ_0035443, hsa_circ_0067557 and hsa_circ_0052661 might regulate these key genes in PE by binding miR-1248 or miR-4303.Key messagesThere is still a lack of predictive and diagnostic factors for preeclampsia, which is a common cause of maternal death worldwide.This study identified a novel circRNA-associated ceRNA network and related pathways in preeclampsia.GNB5 and IL2RB might be key genes in their related circRNA-associated ceRNA network, and probably take an important role in preeclampsia via PI3K-Akt signalling pathway, which made them to be potential markers of preeclampsia.

Fructose is a commonly used food additive and has many adverse effects on human health, but it is unclear whether fructose impacts pulmonary fibrosis. TGF-β1, a potent fibrotic inducer, is produced as latent complexes by various cells, including alveolar epithelial cells, macrophages, and fibroblasts, and must be activated by many factors such as reactive oxygen species (ROS). This study explored the impact of fructose on pulmonary fibrotic phenotype and epithelial-mesenchymal transition (EMT) using lung epithelial cells (A549 or BEAS-2B) and the underlying mechanisms. Fructose promoted the cell viability of lung epithelial cells, while N-Acetyl-l-cysteine (NAC) inhibited such. Co-treatment of fructose and latent TGF-β1 could induce the fibrosis phenotype and the epithelial-mesenchymal transition (EMT)-related protein expression, increasing lung epithelial cell migration and invasion. Mechanism analysis shows that fructose dose-dependently promoted the production of total and mitochondrial ROS in A549 cells, while NAC eliminated this promotion. Notably, post-administration with NAC or SB431542 (a potent TGF-β type I receptor inhibitor) inhibited fibrosis phenotype and EMT process of lung epithelial cells co-treated with fructose and latent TGF-β1. Finally, the fibrosis phenotype and EMT-related protein expression of lung epithelial cells were mediated by the ROS-activated latent TGF-β1/Smad3 signal. This study revealed that high fructose promoted the fibrotic phenotype of human lung epithelial cells by up-regulating oxidative stress, which enabled the latent form of TGF-β1 into activated TGF-β1, which provides help and reference for the diet adjustment of healthy people and patients with fibrosis.

Ovarian cancer is the second most common cause of gynecological cancer death in women. It is usually diagnosed late and accompanied by peritoneal metastasis. For ovarian cancer with peritoneal metastasis, intraperitoneal (IP) chemotherapy can maintain a high drug concentration in the abdominal cavity and reduce local and systemic toxicity. Recently, docetaxel (DTX) has shown broad-spectrum antitumor activity against various malignant tumors, including ovarian cancer with peritoneal metastasis. However, DTX has limited clinical applications due to its poor water solubility, predisposition to hypersensitivity, fluid retention, and varying degrees of neurotoxicity. In this study, we prepared methoxy-poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA) micelles loaded with DTX and developed an alternative, less toxic, more effective DTX formulation, without Tween 80, and evaluated its pharmacokinetics in the abdominal cavity and its efficacy in ovarian cancer with peritoneal metastasis. The mean diameter of DTX-mPEG-PDLLA was about 25 nm, and the pharmacokinetics of BALB/c mice via IP showed that the plasma exposure of DTX-mPEG-PDLLA was about four times lower than that of DTX. Importantly, DTX-mPEG-PDLLA was significantly more effective than DTX and prolonged the survival period in a SKOV-3 ovarian cancer peritoneal metastasis model. Moreover, the apoptosis rate was significantly increased in vitro. Based on these findings, it is expected that DTX-mPEG-PDLLA can enhance efficacy against ovarian cancer peritoneal metastasis, while reducing toxic side effects, and has the potential to be used in the clinical treatment of peritoneal metastatic cancer.

Abstract Background To evaluate the effect of Chrysanthemum morifolium Ramat. ethanol extract (CEE) on lipopolysaccharide induced acute lung injury in mice. Methods The ninety C57BL/6 J male mice randomly divided into five groups: control, model and CEE (50, 100, 200 mg/kg) groups for 7 days oral administration. At the last administration, all mice except control were intratracheal instilled with lipopolysaccharide (LPS, 3 mg/kg) for establish the acute lung injury. Then lung histopathologic, lung wet/dry weight, white blood cells, lymphocytes, neutrophils were detected. The pro-inflammation cytokine tumor necrosis factor-α (TNF-α), interleukin (IL)-6, anti-inflammatory cytokine transforming growth factor-β1 (TGF-β1), IL-10 and the marker of antioxides ability total-antioxidant capacity (T-AOC), malondialdehyde (MDA) in lung tissue were measured. Results The result showed that CEE could improve lung histopathological injury, reduce the ratio of wet/dry lung weight and lung index, inhibit the increased number of white blood cells, lymphocytes and neutrophils, and reduce the increased levels of TNF-α and IL-6. While CEE also significantly increased the levels of TGF-β1 and IL-10. Furthermore, CEE also markedly increased the activity of T-AOC, and decreased the contents of MDA with a dose-dependent manner. Conclusions The study exhibited that CEE has a potential protective effect on lipopolysaccharide induced acute lung injury in mice, the action mechanism of CEE may through balance of the pro-inflammatory and anti-inflammatory factors, and the oxygen free radicals inhibition.

Abstract Thalassemia, classified as the main types α‐ and β‐thalassemia, is a single gene disorder resulting from globin chain synthesis impairment through the mutation or deletion of globin genes. The incidence of thalassemia is high worldwide, with high associated mortality. Therefore, treatment is important to improve patient outcomes. This paper reviews the current status of β‐thalassemia major in China, including its epidemiology and treatment.

ObjectiveMindfulness-based interventions have been widely demonstrated to be effective in reducing stress, alleviating mood disorders, and improving quality of life; however, the underlying mechanisms remained to be fully understood. Along with the advanced research in the microbiota-gut-brain axis, this study aimed to explore the impact of gut microbiota on the effectiveness and responsiveness to mindfulness-based cognitive therapy (MBCT) among high trait anxiety populations.DesignA standard MBCT was performed among 21 young adults with high trait anxiety. A total of 29 healthy controls were matched for age and sex. The differences in gut microbiota between the two groups were compared. The changes in fecal microbiota and psychological indicators were also investigated before and after the intervention.ResultsCompared with healthy controls, we found markedly decreased bacterial diversity and distinctive clusters among high trait anxiety populations, with significant overgrowth of bacteria such as Streptococcus, Blautia, and Romboutsia, and a decrease in genera such as Faecalibacterium, Coprococcus_3, and Lachnoclostridium. Moreover, MBCT attenuated trait anxiety and depression, improved mindfulness and resilience, and increased the similarity of gut microbiota to that of healthy controls. Notably, a high presence of intestinal Subdoligranulum pre-MBCT was associated with increased responsiveness to MBCT. Decreases in Subdoligranulum post-MBCT were indicative of ameliorated trait anxiety. The tryptophan metabolism pathways were significantly over-represented among high responders compared to low responders.ConclusionThe significantly increased diversity post-MBCT added evidence to gut-brain communication and highlighted the utility of mycobiota-focused strategies for promoting the effectiveness and responsiveness of the MBCT to improve trait anxiety.Clinical Trial Registrationchictr.org.cn, ChiCTR1900028389.

Editor's Note: this Article has been retracted; the Retraction Note is available at https://doi.org/10.1038/s41598-021-83145-9 .

Background: The prevalence of mental illness continues to increase in China, but research on stigma is still in its infancy, and there are even fewer studies on stigma among nurses. A comprehensive, effective and reliable tool is needed to assess stigma in nursing so that it can be reduced or eliminated to improve nursing quality. This study aimed to translate a 20-item scale for assessing the stigma of mental illness in nursing into Chinese and evaluate its reliability and validity.Methods: An improved Brislin translation model was used to translate the nursing mental illness stigma assessment scale into Chinese. Content and face validity were determined by a panel of experts. A convenience sample of 501 nursing students was chosen. Confirmatory factor analysis, concurrent validity and known group comparison were used to evaluate the scale's structural validity. The reliability was evaluated based on the internal consistency reliability and 2-week retest reliability.Results: The content validity index was 0.90. Confirmatory factor analysis showed that this study supported the three-factor model. The moderate correlation between the Chinese version of the Scale for Assessing the Stigma of Mental Illness in Nursing and the Perceived Devaluation Discrimination Scale suggested acceptable concurrent validity. Cronbach's α (0.863) and the retest coefficient (0.839) were indicative of internal consistency.Conclusion: The Chinese version of the Scale for Assessing the Stigma of Mental Illness in Nursing has acceptable concurrent validity, marginal factor validity, and satisfactory reliability in China. Therefore, the three-factor structure of the Chinese scale should be considered.Relevance to Clinical Practice: The Chinese version of the Scale for Assessing the Stigma of Mental Illness in Nursing can be used to understand the degree of mental illness stigma in nursing.

In the global context of sustainable urban development, urban regeneration is an activity to improve the form and function of urban space in built-up areas. Commercial streets are one of the most active factors in urban space and an important factor in promoting urban prosperity and reflecting urban vitality, yet these streets have not kept pace with the public’s quest for quality through theoretical change, and this can even affect public comfort and well-being. In order to effectively undertake urban regeneration and improve the quality of urban streets and residents’ satisfaction, design factors for the quality enhancement of commercial streets are explored in order to rationalise residents’ demand preferences and their priorities, enhance residents’ sense of belonging, and provide suggestions for the optimisation of the design of subsequent urban street regeneration in China. By summarising the literature and the content requirements of the quality enhancement scheme for Shuanggang Old Street in Hefei, this study applied a questionnaire survey and scientifically developed an index system containing five evaluation indicators, including spatial carrying capacity, street attractiveness, travel safety, environmental comfort, and social interaction. A combination of hierarchical analysis and entropy weighting was used to identify the most influential factors on the implementation of the quality improvement of the commercial street and design optimisation suggestions. The evaluation results show that travel safety and social interaction significantly affect the evaluation of the quality improvement of commercial streets, as well as highlighting the needs of residents for street environments and services and the role of local governments.

With the acceleration of urbanization, the demand for land due to urban large-scale construction and development is increasing. Coastal reclamation (CR) is a prevailing approach to tackle the contradiction between coastal land shortage and the growing demand for living space for human beings. Enormous social and economic benefits are derived from CR, while at the same time bringing a series of environmental problems. Since the beginning of the 21st century, this oceanic-oriented development has become more frequent. Therefore, the considerable economic and ecological trade-offs of reclamation activities must be analyzed to enable targeted land use decisions. By comprehensively evaluating the natural conditions of the sea area, including geology, topography, hydrology, ecology, and social and economic conditions, this study established an environmental capacity assessment system (ECAS) based on water environmental capacity for assessment of the potential environmental impact resulting from CR. According to the water quality status and positions of CR in Haizhou Bay, the environmental capacities of four major pollutants were calculated to forecast the suitable area of CR. The results indicated that these reclamation projects had notable negative effects on the environmental capacity of the four major pollutants. The order of pollutants according to their harm on seawater quality is: PO4-P > NH4-N > NOX-N > COD. In three reclamation alternative scenarios, scenario 3 led to the minimum negative impacts on the environmental capacity, scenario 2 followed, and scenario 1 had the worst result. Hence, scenario 3 was the optimal reclamation scenario, under which the suitable area of CR in Haizhou Bay was found to be 83 km2. This study provides a scientific reference for the effective management of coastal reclamation and future environmental impact research when new CR is proposed, as well as sustainable urban development.

Colorectal cancer (CRC) is the third most common cancer worldwide and still lacks effective therapy. Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. However, whether ivermectin affects CRC is still unclear. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. We used CCK-8 assay to determine the cell viability, used an optical microscope to measure cell morphology, used Annexin V-FITC/7-AAD kit to determine cell apoptosis, used Caspase 3/7 Activity Apoptosis Assay Kit to evaluate Caspase 3/7 activity, used Western blot to determine apoptosis-associated protein expression, and used flow cytometry and fluorescence microscope to determine the reactive oxygen species (ROS) levels and cell cycle. The results demonstrated that ivermectin dose-dependently inhibited colorectal cancer SW480 and SW1116 cell growth, followed by promoting cell apoptosis and increasing Caspase-3/7 activity. Besides, ivermectin upregulated the expression of proapoptotic proteins Bax and cleaved PARP and downregulated antiapoptotic protein Bcl-2. Mechanism analysis showed that ivermectin promoted both total and mitochondrial ROS production in a dose-dependent manner, which could be eliminated by administering N-acetyl-l-cysteine (NAC) in CRC cells. Following NAC treatment, the inhibition of cell growth induced by ivermectin was reversed. Finally, ivermectin at low doses (2.5 and 5 µM) induced CRC cell arrest. Overall, ivermectin suppressed cell proliferation by promoting ROS-mediated mitochondrial apoptosis pathway and inducing S phase arrest in CRC cells, suggesting that ivermectin might be a new potential anticancer drug therapy for human colorectal cancer and other cancers.

Histone deacetylase inhibitors are currently the most studied drugs because of their beneficial effects on inflammatory response. Emerging data from numerous basic studies and clinical trials have shown that histone deacetylase inhibitors can suppress immune-mediated diseases, such as graft-vs.-host disease (GVHD), while retaining beneficial graft-vs.-leukemia (GVL) effects. These drugs prevent and/or treat GVHD by modifying gene expression and inhibiting the production of proinflammatory cytokines, regulating the function of alloreactive T cells, and upregulating the function and number of regulatory T cells. Some of these drugs may become new immunotherapies for GVHD and other immune diseases.

Widely known for self-renewal and multilineage differentiation, stem cells can be differentiated into all specialized tissues and cells in the body. In the past few years, a number of researchers have focused on deriving hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) as alternative sources for clinic. Existing findings demonstrated that it is feasible to obtain HSCs and certain mature blood lineages from PSCs, except for several issues to be addressed. This short review outlines the technologies used for hematopoietic differentiation in recent years. In addition, the therapeutic value of PSCs as a potential source of various blood cells is also discussed as well as its challenges and directions in future clinical applications.

Background: Microbial communities and their metabolic components in the gut are of vital importance for immune homeostasis and have an influence on the susceptibility of the host to a number of immune-mediated diseases like acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the functional connections between microbiome and metabolome in aGVHD due to the complexity of the gastrointestinal environment. Method: Initially, gut microbiota and fecal metabolic phenotype in aGVHD murine models were unleashed by performing 16S ribosomal DNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics. Findings: The group with aGVHD experienced a significant drop in Lachnospiraceae_unclassified but an increase in the relative abundance of Clostridium XI, Clostridium XIVa and Enterococcus. Meanwhile, a lower content of tyrosine was observed in the gut of aGVHD mice. The correlation analysis revealed that tyrosine-related metabolites were inversely correlated with Clostridium XIVa, besides, Blautia and Enterococcus also displayed the negative tendency in aGVHD condition. Apart from exploring the importance and function of tyrosine, different tyrosine diets were offered to mice during transplantation. Additional tyrosine supplements can improve overall survival, ameliorate symptoms at the early stage of aGVHD and change the structure and composition of gut microbiota and fecal metabolic phenotype. In addition, aGVHD mice deprived from tyrosine displayed worse manifestations than the vehicle diet group. Interpretation: The results demonstrated the roles and mechanisms of gut microbiota, indispensable metabolites and tyrosine in the progression of aGVHD, which can be an underlying biomarker for aGVHD diagnosis and treatment. Funding: This research was funded by the International Cooperation and Exchange Program (81520108002), the National Key R&D Program of China, Stem Cell and Translation Research (2018YFA0109300), National Natural Science Foundation of China (81670169, 81670148, 81870080 and 91949115) and Natural Science Foundation of Zhejiang Province (LQ19H080006).

The purpose of this study is to examine how the emotion regulation strategy, cognitive reappraisal, affects the association between perceived stress and anxiety symptoms in COVID-19 isolated people. Data for this cross-sectional study come from a community-based online survey of COVID-19 isolated people (N = 328), who are not infected with the 2019-nCoV virus. We applied correlation and moderating effect for data analysis and found that cognitive reappraisal negatively moderated the relationship between perceived stress and anxiety symptoms. These results give us a new perspective on understanding the relationship between anxiety symptoms and perceived stress by clarifying the protective function of cognitive reappraisal. It buffers the induced negative emotion when COVID-19 isolated people perceive overpressure, and thus instigates future research into targeted clinical interventions, which aim to cultivate cognitive reappraisal skills for those isolated people in the face of stressful events or crisis events.

Abstract Background To investigate the relationships among phenotypes, genotypes, and funotypes of SCN2A‐related developmental epileptic encephalopathy (DEE). Methods We enrolled five DEE patients with five de novo variants of the SCN2A. Functional analysis and pharmacological features of Nav1.2 channel protein expressed in HEK293T cells were characterized by whole‐cell patch‐clamp recording. Results The phenotypes of c.4712T>C(p. I1571T), c.2995G>A(p.E999K), and c.4015A>G(p. N1339D) variants showed similar characteristics, including early seizure onset with severe to profound intellectual disability. Electrophysiological recordings revealed a hyperpolarizing shift in the voltage dependence of the activation curve and smaller recovery time constants of fast‐inactivation than in wild type, indicating a prominent gain of function (GOF). Moreover, pharmacological electrophysiology showed that phenytoin inhibited over a 70% peak current and was more effective than oxcarbazepine and carbamazepine. In contrast, c.4972C>T (p.P1658S) and c.5317G>A (p.A1773T) led to loss of function (LOF) changes, showing reduced current density and enhanced fast inactivation. Both showed seizure onset after 3 months of age with moderate development delay. Interestingly, we discovered that choreoathetosis was a specific phenotype feature. Conclusion These findings provided the insights into the phenotype–genotype–funotype relationships of SCN2A‐related DEE. The preliminary evaluation using the distinct hints of GOF and LOF helped plan the treatment, and the next precise step should be electrophysiological study.

Nasopharyngeal carcinoma (NPC) is a malignant tumor in South China, characterized with high death rate. If untreated, NPC cells will be invasiveness and then spread to other tissues. In clinical practice, however, lack of early effective screening to prevent the NPC development. Therefore, candidate biomarker for detecting NPC is developing urgently. In current study, human NPC data and samples were collected for tests, followed by cell culture study. As results, Epstein-Barr virus (EBV)-based human NPC sections showed increased expressions of heat shock protein 90 (Hsp90), protein kinase B (AKT), and Hsp90 levels were positively expressed than those in cytokeratin 19 (CK19). The clinical data showed unchanged contents of blood cancer markers. In cell line study, Hsp90-treated cells (CNE1, 5–8 F) resulted in promoted cellular growth and proliferation. Additionally, proliferative proteins of cellular extracellular regulated protein kinase (Erk1/2), phospho-Erk1/2 (Thr202+Tyr204), B-cell lymphoma-2 (Bcl-2), AKT, phospho-AKT (Ser473), Ki-67 were up-regulated in Hsp90 treatments, while the apoptotic protease activating factor-1 (Apaf1) were down-regulated. Followed by treatment with Hsp90 inhibitor, the NPC cells exhibited inhibited cellular proliferation and growth, induced cell apoptosis, reduced proliferative proteins of Erk1/2, phospho-Erk1/2 (Thr202+Tyr204), AKT, phospho-AKT (Ser473), Bcl-2, Ki-67, and elevated Apaf1 expression. In conclusion, the current findings obtained from this study demonstrate that Hsp90 effectively promotes cell proliferation through activating carcinomatous ERK1/2, phospho-Erk1/2 (Thr202+Tyr204), AKT, phospho-AKT (Ser473) expressions in NPC cells. Briefly, Hsp90 may be a promising biomarker to screen NPC, including early stage.

The redevelopment of urban villages is a prominent part of urban renewal in China, which has attracted much attention from the academic community. However, the understanding of when and where the redevelopment of urban villages occurs is still limited partly because of the lack of empirical analysis. Through exploratory spatial data and overlay analyses, this study examines the spatio-temporal distribution characteristics based on data from 277 urban village redevelopment projects in Shenzhen, China, between 2010 and 2018. Results demonstrate that the redevelopment of urban villages occurs in central and suburban areas but rarely occurs in the periphery of the city. The overall spatial distribution is spatially clustered, having become increasingly significant from 2010 to 2018. In the beginning, the redevelopment of urban villages was dispersed in diverse areas and partly expanded into adjacent neighbourhoods. A majority of redevelopment took place in areas near the planning urban centres and the planning subway stations, which are almost in Density Zones I–III. The findings of this study contribute to new spatio-temporal perspectives in the global process mechanism of urban village redevelopment and call for special attention to the significant influences of state intervention, which is an informative reference for future sustainable urban development.

Oviductus ranae (OR) is a traditional Chinese medicine, which was first recorded in the Compendium of Materia Medica in the Ming Dynasty. OR contains high amounts of proteins and elicits therapeutic effects on neurasthenia, insomnia, and respiratory symptoms, which are related to oxidative stress and immunodeficiency. This study aimed to obtain the potential of OR for the development of functional food possessing antioxidant and immune-enhancement functions in the same dose. In antioxidant evaluation, OR can significantly decrease malondialdehyde and protein carbonyls (P < 0.05, P < 0.01) and significantly increase total superoxide dismutase and glutathione in a dose-dependent manner (P< 0.05, P < 0.01) against ethanol-induced oxidative stress in mice at 0.1, 1.0, and 3.0 g/kg BW. In immunomodulatory evaluation, OR could significantly enhance the phagocytosis of liver macrophages (P < 0.05, P < 0.01), delayed-type hypersensitivity response (P < 0.05, P < 0.01), hemolytic activity (P < 0.05), antibody-producing cells (P < 0.05), and natural killer cell activity (P < 0.05) in the same dose range described in antioxidant evaluation compared with those in the normal control. OR slightly influenced lymphocyte proliferation, peritoneal macrophage phagocytosis, and immune organ indices in mice. Thus, 3.0 g/kg BW OR showed potential for the development of functional food with antioxidant and immune-enhancement activities.