Search

The small-scale linear information in galaxy samples typically lost during nonlinear growth can be restored to a certain level by the density field reconstruction, which has been demonstrated for improving the precision of the baryon acoustic oscillation (BAO) measurements. As proposed in the literature, a joint analysis of the power spectrum before and after the reconstruction enables an efficient extraction of information carried by high-order statistics. However, the statistics of the postreconstruction density field are difficult to model. In this work, we circumvent this issue by developing an accurate emulator for the prereconstructed, postreconstructed, and cross-power spectra ( ${P}_{\mathrm{pre}}$ , P _post , P _cross ) up to k = 0.5 h Mpc ^−1 based on the Dark Quest N -body simulations. The accuracy of the emulator is at the percent level; namely, the error of the emulated monopole and quadrupole of the power spectra is less than 1% and 10% of the ground truth, respectively. A fit to an example power spectrum using the emulator shows that the constraints on cosmological parameters get largely improved using ${P}_{\mathrm{pre}}$ + P _post + P _cross with ${k}_{\max }=0.25\,h\,{\mathrm{Mpc}}^{-1}$ , compared to that derived from ${P}_{\mathrm{pre}}$ alone; namely, the constraints on (Ω _m , H _0 , σ _8 ) are tightened by ∼41%–55%, and the uncertainties of the derived BAO and RSD parameters ( α _⊥ , α _∣∣ , f σ _8 ) shrink by ∼28%–54%, respectively. This highlights the complementarity among ${P}_{\mathrm{pre}}$ , P _post , and P _cross , which demonstrates the efficiency and practicability of a joint ${P}_{\mathrm{pre}}$ , P _post , and P _cross analysis for cosmological implications.

Human respiratory syncytial virus (HRSV) poses a significant disease burden on global health. To date, two vaccines that primarily induce humoral immunity to prevent HRSV infection have been approved, whereas vaccines that primarily induce T-cell immunity have not yet been well-represented. To address this gap, 25 predicted T-cell epitope peptides derived from the HRSV fusion protein with high human leukocyte antigen (HLA) binding potential were synthesized, and their ability to be recognized by PBMC from previously infected HRSV cases was assessed using an ELISpot assay. Finally, nine T-cell epitope peptides were selected, each of which was recognized by at least 20% of different donors’ PBMC as potential vaccine candidates to prevent HRSV infection. The protective efficacy of F-9PV, a combination of nine peptides along with CpG-ODN and aluminum phosphate (Al) adjuvants, was validated in both HLA-humanized mice (DR1-TCR transgenic mice, Tg mice) and wild-type (WT) mice. The results show that F-9PV significantly enhanced protection against viral challenge as evidenced by reductions in viral load and pathological lesions in mice lungs. In addition, F-9PV elicits robust Th1-biased response, thereby mitigating the potential safety risk of Th2-induced respiratory disease during HRSV infection. Compared to WT mice, the F-9PV mice exhibited superior protection and immunogenicity in Tg mice, underscoring the specificity for human HLA. Overall, our results demonstrate that T-cell epitope peptides provide protection against HRSV infection in animal models even in the absence of neutralizing antibodies, indicating the feasibility of developing an HRSV T-cell epitope peptide-based vaccine.

Discogenic back pain, a subset of chronic back pain, is caused by intervertebral disc (IVD) degeneration, and imparts a notable socioeconomic health burden on the population. However, degeneration by itself does not necessarily imply discogenic pain. In this review, we highlight the existing literature on the pathophysiology of discogenic back pain, focusing on the biomechanical and biochemical steps that lead to pain in the setting of IVD degeneration. Though the pathophysiology is incompletely characterized, the current evidence favors a framework where degeneration leads to IVD inflammation, and subsequent immune milieu recruitment. Chronic inflammation serves as a basis of penetrating neovascularization and neoinnervation into the IVD. Hence, nociceptive sensitization emerges, which manifests as discogenic back pain. Recent studies also highlight the complimentary roles of low virulence infections and central nervous system (CNS) metabolic state alteration. Targeted therapies that seek to disrupt inflammation, angiogenesis, and neurogenic pathways are being investigated. Regenerative therapy in the form of gene therapy and cell-based therapy are also being explored.

Nepal has experienced severe fine particulate matter (PM2.5) pollution in recent years. However, few studies have focused on the distribution of PM2.5 and its variations in Nepal. Although many researchers have developed PM2.5 estimation models, these models have mainly focused on the kilometer scale, which cannot provide accurate spatial distribution of PM2.5 pollution. Based on Gaofen-1/6 and Landsat-8/9 satellite data, we developed a stacked ensemble learning model (named XGBLL) combined with meteorological data, ground PM2.5 concentrations, ground elevation, and population data. The model includes two layers: a XGBoost and Light GBM model in the first layer, and a linear regression model in the second layer. The accuracy of XGBLL model is better than that of a single model, and the fusion of multi-source satellite remote sensing data effectively improves the spatial coverage of PM2.5 concentrations. Besides, the spatial distribution of the daily mean PM2.5 concentrations in the Kathmandu region under different air conditions was analyzed. The validation results showed that the monthly averaged dataset was accurate (R2 = 0.80 and root mean square error = 7.07). In addition, compared to previous satellite PM2.5 datasets in Nepal, the dataset produced in this study achieved superior accuracy and spatial resolution.

Ferroptosis, a form of regulated cell death, was first defined in 2012. Ferroptosis mainly involves iron-driven lipid peroxidation damage of cells. This process is regulated by iron homeostasis, redox balance, lipid metabolism, glutathione metabolism, and various disease signaling pathways. Iron is one of the key mineral elements that regulate the physiological function of women and the development of ovarian tumors. Occurrence of Ferroptosis has some hidden dangers and advantages in ovary diseases. Some scholars have shown that ferroptosis of ovarian granulosa cells (GC) promotes the development of ovarian dysfunction and polycystic ovary syndrome (PCOS). Interestingly, drug-resistant ovarian cancer cells are very sensitive to ferroptosis, suggesting that pharmacological positive and negative regulation of ferroptosis has great potential in the treatment of benign ovarian diseases and ovarian cancer. This article aimed to assess how ferroptosis occurs and the factors controlling ferroptosis. Moreover, we summarize how ferroptosis can be used to predict, diagnose and target treatment ovary disease. Meanwhile, we also evaluated the different phenomena of Ferroptosis in ovarian diseases. It aims to provide new directions for the research and prevention of female reproductive diseases.

Background: Cisplatin resistance is a common clinical problem in lung cancer. However, the underlying mechanisms have not yet been fully elucidated, highlighting the importance of searching for biological targets.Methods: Bioinformatics analysis is completed through downloaded public data (GSE21656, GSE108214, and TCGA) and specific R packages. The evaluation of cell proliferation ability is completed through CCK8 assay, colony formation, and EdU assay. The evaluation of cell invasion and migration ability is completed through transwell and wound-healing assays. In addition, we evaluated cell cisplatin sensitivity by calculating IC50.Results: Here, we found that PCDH7 may be involved in cisplatin resistance in lung cancer through public database analysis (GSE21656 and GSE108214). Then, a series of in vitro experiments was performed, which verified the cancer-promoting role of PCDH7 in NSCLC. Moreover, the results of IC50 detection showed that PCDH7 might be associated with cisplatin resistance of NSCLC. Next, we investigated the single-cell pattern, biological function, and immune analysis of PCDH7. Importantly, we noticed PCDH7 may regulate epithelial–mesenchymal transition activity, and the local infiltration of CD8+ T and activated NK cells. Furthermore, we noticed that patients with high PCDH7 expression might be more sensitive to bortezomib, docetaxel, and gemcitabine, and resistant to immunotherapy. Finally, a prognosis model based on three PCDH7-derived genes (GPX8, BCAR3, and TNS4) was constructed through a machine learning algorithm, which has good prediction ability on NSCLC patients’ survival.Conclusion: Our research has improved the regulatory framework for cisplatin resistance in NSCLC and can provide direction for subsequent related research, especially regarding PCDH7.

BackgroundLynch syndrome (LS)-associated glioblastoma (GBM) is rare in clinical practice, and simultaneous occurrence with cutaneous porokeratosis is even rarer. In this study, we analyzed the clinicopathological and genetic characteristics of LS-associated GBMs and concurrent porokeratosis, as well as evaluated the tumor immune microenvironment (TIME) of LS-associated GBMs.MethodsImmunohistochemical staining was used to confirm the histopathological diagnosis, assess MMR and PD-1/PD-L1 status, and identify immune cell subsets. FISH was used to detect amplification of EGFR and PDGFRA, and deletion of 1p/19q and CDKN2A. Targeted NGS assay analyzed somatic variants, MSI, and TMB status, while whole-exome sequencing and Sanger sequencing were carried out to analyze the germline mutations.ResultsIn the LS family, three members (I:1, II:1 and II:4) were affected by GBM. GBMs with loss of MSH2 and MSH6 expression displayed giant and multinucleated bizarre cells, along with mutations in ARID1A, TP53, ATM, and NF1 genes. All GBMs had TMB-H but not MSI-H. CD8+ T cells and CD163+ macrophages were abundant in each GBM tissue. The primary and recurrent GBMs of II:1 showed mesenchymal characteristics with high PD-L1 expression. The family members harbored a novel heterozygous germline mutation in MSH2 and FDPS genes, confirming the diagnosis of LS and disseminated superficial actinic porokeratosis.ConclusionLS-associated GBM exhibits heterogeneity in clinicopathologic and molecular genetic features, as well as a suppressive TIME. The presence of MMR deficiency and TMB-H may serve as predictive factors for the response to immune checkpoint inhibitor therapy in GBMs. The identification of LS-associated GBM can provide significant benefits to both patients and their family members, including accurate diagnosis, genetic counseling, and appropriate screening or surveillance protocols. Our study serves as a reminder to clinicians and pathologists to consider the possibility of concurrent genetic syndromes in individuals or families.

In this study, we investigated the effect of particle size distribution on the shear properties of sand. Direct shear tests were conducted using four types of sand samples with different particle size distributions obtained from standard sand produced by Xiamen ISO Co. Ltd. The results show that the influence of particle size distribution on the internal friction angle was significant. Typically, the internal friction angle increases with increasing the coefficient of non-uniformity (Cu) and decreasing the curvature coefficient (Cc). The discrete element results show that the initial particle size distribution significantly affects the porosity, coordination number, and particle slide fraction. In addition, the grey relation analysis revealed that the sliding fraction and coordination number have the greatest correlation with the internal friction angle. The research results of this study help to understand the changes in particle contact, internal stress, and particle sliding during the shear failure process of sand.

SARS-CoV-2 binds to ACE2 receptors, expressed within the lungs. Risk factors for hospitalization include hypertension, diabetes, ischaemic heart disease and obesity–conditions linked by the presence of endothelial pathology. Viral infection in this setting causes increased conversion of circulating Factor XII to its active form (FXIIa). This is the first step in the contact-kinin pathway, leading to synchronous activation of the intrinsic coagulation cascade and the plasma Kallikrein-Kinin system, resulting in clotting and inflammatory lung disease. Temporal trends are evident from blood results of hospitalized patients. In the first week of symptoms the activated partial thromboplastin time (APTT) is prolonged. This can occur when clotting factors are consumed as part of the contact (intrinsic) pathway. Platelet counts initially fall, reflecting their consumption in coagulation. Lymphopenia occurs after approximately 1 week, reflecting the emergence of a lymphocytic pneumonitis [COVID-19 acute respiratory distress syndrome (ARDS)]. Intrinsic coagulation also induces the contact-kinin pathway of inflammation. A major product of this pathway, bradykinin causes oedema with ground glass opacities (GGO) on imaging in early COVID-19. Bradykinin also causes release of the pleiotrophic cytokine IL-6, which causes lymphocyte recruitment. Thromobosis and lymphocytic pneumonitis are hallmark features of COVID-19 ARDS. In this review we examine the literature with particular reference to the contact-kinin pathway. Measurements of platelets, lymphocytes and APTT should be undertaken in severe infections to stratify for risk of developing ARDS.

In this paper, an experimental approach is employed to investigate the reinforcing impact of geogrids on the dry-shrinkage cracking of loess. At various evaporation temperatures and for varying specimen thicknesses, the evolution of the surface fissures induced in the loess samples with and without geogrids was monitored and analyzed. According to the findings, the evaporation rate of the samples increased when the evaporation temperature was increased, and the thickness of the samples was reduced under the same conditions. At higher temperatures, geogrids had a substantial impact on reducing the evaporation rate and suppressing the dry-shrinkage cracks. The occurrence and development of the dry-shrinkage cracks of loess are divided into three stages: the formation stage, the acceleration stage, and the stabilization stage. The maximum crack width was reduced by 20%–34% for different sample thicknesses. The ratio of the number of cracks to the number of fracture nodes in the reinforced soil was lower than that of the unreinforced soil. This reduction ratio changed further from 5.6% to 24.4% with the increased thickness. The geogrids can effectively reduce the evaporation rate of water and the development rate of the dry-shrinkage cracks in loess. Consequently, the crack distribution in the loess samples is uniform and prevents the formation of large and long cracks. Using a 3D discrete element model, it is feasible to simulate the loess before and after the geogrid reinforcement.

Background: Platelet lysate (PL), a novel platelet derivative, has been widely used in regenerative medicine and is a potential therapy for improving hair growth. It is necessary to fully clarify the potential mechanism and evaluate preliminary clinical effect of PL on hair growth. Methods: We used the C57BL/6 model, organ-cultured hair follicles, and RNA-seq analysis to explore the mechanisms of PL regulating hair growth. Then, we performed a randomized, controlled, double-blind study of 107 AGA patients to verify the therapeutic efficacy of PL. Results: The results confirmed that PL improved hair growth and accelerated hair cycling in mice. Organ-cultured hair follicle evaluation confirmed that PL prolonged anagen remarkably and down-regulated IL-6, C-FOS, and p-STAT5a. Clinically, diameter, hair counts, absolute anagen counts and changes from baseline in the PL group showed a significant improvement at 6 months. Conclusions: We elucidated the specific molecular mechanism of PL action on hair growth and proved equal changes in hair follicle performance after PL vs PRP in AGA patients. This study provided novel knowledge of PL, making it ideal for AGA.

Abstract Many degradation processes of cultural heritage objects are associated with unsuitable microclimatic conditions. One of the most ubiquitous deteriorations is the crystallization of salts in pores, which can accelerate the erosion rate of masonry historical relics. In this study, the microclimate of the burial tomb and exfoliation of sandstone in the Yongling Mausoleum of the Former Shu Dynasty in Chengdu were monitored for 1 year to determine the development of the degradation. We established a connection between the monitoring data and exfoliation variations of the stone with time. To predict the deterioration of the stone, a three-dimensional computational finite element model was used to simulate the detailed process of the thermo-hygrometric performance that led to salt crystallization and artwork deterioration. Two results were obtained. In the simulation of the microclimate, the temperature ranged from 15 to 22.6 °C, and the relative humidity was heterogeneous and varied between 60 and 100%. The other was the relationship between the microclimate and exfoliation. It was found that the exfoliation was more severe in the higher relative humidity areas where the water vapor frequently interacted with the relics. The crystallization and hydration of sulfate produced stress, which damaged the stone relics. These results provide a rationale analysis and a reference for better management of the environmental interactions and reduction of the environmental impacts in the subsequent scientific conservation of ancient Chinese cultural relics in tombs.

Abstract Two-dimensional (2D) magnetoelectric (ME) materials with spontaneous magnetism and polarity have drawn a lot of research interest due to their potentially valuable physics and spintronic applications. One of the obstacles in the current study of 2D ME materials is to achieve flexible magnetism/polarity switches because of a fundamental contradiction between magnetism and polarity. In this work, we propose an intrinsic magnetism/polarity switchable 2D Janus structure Cr2I3Y3 (Y = F, Cl, or Br) with mechanical and thermodynamic stability. Janus Cr2I3Y3 monolayers show indirect-gap semiconductors with ferromagnetic ordering. Intrinsic vertical electric polarity (EP) in Janus Cr2I3Y3 structures is investigated by surface potential difference analysis and dipole calculations. We discover that there is an obvious ME coupling between magnetic anisotropy energy (MAE) and EP. MAE can be obviously tuned by rotating the orientations of spins within yz and zx vertical planes, and the easily distinguishable MAE on vertical planes has strong inherent relevance with vertical EP. Simultaneously, magnetic phase transition and magnetic moments can be manipulated by introducing vertical strain, which directly corresponds to the linear response of the EP strength. Our work provides a promising candidate for realizing the spintronic devices with multiple functionalities.

Chemoprevention of hepatocellular carcinoma (HCC) is highly desirable in clinic. Berberine (BBR) is reported to play potential roles in cancer treatment and prevention. We studied the chemopreventive effect of BBR on hepatocellular carcinogenesis in an inflammation-driven mouse model, as it was enriched in liver after oral administration. Oral BBR significantly decreased the number and volume of visible nodular tumors, and prolonged the median overall survival by 9 and 8 weeks in the diethylnitrosamine (DEN)-injected male and female mice respectively. The nodular tumors were induced through activation of the lysophosphatidic acid (LPA) pathway in liver. LPA stimulated the abnormal leptin transcription through interacting with LPA receptor-2 (LPAR2) followed by p38 activation, and BBR inhibited carcinogenesis by suppressing the bioactivity of LPA. Specifically, BBR significantly reduced the expression of the LPA synthetase autotaxin (ATX) and LPAR2 in the nodular tumors of DEN-injected mice. Subsequently, BBR repressed the abnormal transcription of leptin stimulated by LPA-induced phosphorylation of p38 in hepatoma cells. In fact, BBR reduced the abnormal expression of leptin in livers of DEN-injected male mice throughout the course of an 8-month experiment. BBR might be a preventive agent for HCC, working at least partially through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in liver.

Diabetic retinopathy(DR), one of the common complications of diabetes, is a major cause of blindness. Traditionally, DR has been considered primarily a microvascular disease, and as research has progressed, it is now believed that disruption of the neuro-glia-vascular unit(NVU)and imbalance in its coupling mechanisms(coupling)play a key role in the early onset of DR. Understanding the cellular and molecular basis of NVU and how diabetes alters normal cellular communication and disrupts the cellular environment is important for the early prevention and treatment of DR. This paper summarizes the retinal NVU and its involvement in the molecular mechanism of DR pathogenesis, DR treatment based on retinal NVU repair, and discusses the future prospects and problems of DR.

Background Aquatic therapeutic exercise is an emerging physical therapy technique, which provides new ideas for improving the motor function and quality of life of patients with stroke. However, it is not clear that the rehabilitation benefits obtained by patients with stroke from aquatic therapeutic exercise, and the levels of methodological quality and evidence quality of relevant studies. Objective To overview the systematic reviews of aquatic therapeutic exercise in improving the rehabilitation in patients with stroke. Methods In June 2021, Systematic reviews assessing the effects of aquatic therapeutic exercise in stroke rehabilitation were searched in databases of PubMed, the Cochrane Library, EmBase, CINAHL, Web of Science, CNKI, WanFang Data, CQVIP and SinoMed from inception to June 15, 2021. Two researchers screened systematic reviews according to the inclusion and exclusion criteria and extracted data separately. The methodological quality was evaluated using AMSTAR 2. The reporting quality was evaluated using the PRISMA. The quality of evidence for major outcomes was evaluated using the GRADE system. Results A total of 9 reviews were included, 2 of which were in Chinese and 7 were in English. The analysis showed that the methodological quality of 1, 1, and 7 reviews were moderate, low, and extremely low, respectively. The reporting quality of 7 reviews were relatively complete, 1 review had some flaws, and 1 review had a serious information flaw. There were a total of 9 outcome indicators, and 49 bodies of evidence, and the quality of bodies of evidence was mostly low or very low. Aquatic therapeutic exercise improved the balance function, mobility and muscle strength of stroke patients to a certain extent. And the rehabilitation benefits had proven to be more when it was used in combination with dryland trainings. Conclusion Aquatic therapeutic exercise has proven to be effective in improving balance function, mobility and muscle strength in stroke patients with good safety. But the overall methodological quality and quality of evidence for major outcomes of included systematic reviews are unsatisfactory. It is suggested that future studies use a larger sample size and an improved design, which will provide evidence-based guidance for clinical management of stroke rehabilitation with aquatic therapeutic exercise.

Objective In this study, we aimed to identify long non-coding RNAs (lncRNAs) that play important roles in starvation stress, analyze their functions, and discover potential molecular targets to alleviate starvation stress to provide a theoretical reference for subsequent in-depth research. Methods We generated a piglet starvation stress animal model. Nine Yorkshire weaned piglets were randomly divided into a long-term starvation stress group (starved for 72 h), short-term starvation stress group (starved for 48 h), and the control group. LncRNA libraries were constructed using high-throughput sequencing of piglet ileums. Results We obtained 11,792 lncRNAs, among which, 2,500 lncRNAs were novel. In total, 509 differentially expressed (DE)lncRNAs were identified in this study. Target genes of DElncRNAs were predicted via cis and trans interactions, and functional and pathway analyses were performed. Gene ontology functions and Kyoto encyclopedia of genes and genomes analysis revealed that lncRNA-targeted genes mainly participated in metabolic pathways, cellular processes, immune system processes, digestive systems, and transport activities. To reveal the mechanism underlying starvation stress, the interaction network between lncRNAs and their targets was constructed based on 26 DElncRNAs and 72 DEmRNAs. We performed an interaction network analysis of 121 DElncRNA–DEmRNA pairs with a Pearson correlation coefficient greater than 0.99. Conclusion We found that MSTRG.19894.13, MSTRG.16726.3, and MSTRG.12176.1 might play important roles in starvation stress. This study not only generated a library of enriched lncRNAs in piglets, but its outcomes also provide a strong foundation to screen key lncRNAs involved in starvation stress and a reference for subsequent in-depth research.

Abstract Background Pomalidomide in combination with dexamethasone has demonstrated positive results in patients with relapsed or refractory multiple myeloma (RRMM), but no data are available in China. We conducted a multicenter, single-arm trial to examine the efficacy and safety of bioequivalent generic pomalidomide plus low-dose dexamethasone in Chinese RRMM patients. Methods Adult (≥ 18 years of age) RRMM patients who progressed after at least two previous treatments, including bortezomib and lenalidomide, were eligible. Pomalidomide was given orally at 4 mg/day on days 1 to 21 of a 28-day cycle. Dexamethasone was given at 40 mg/day (either orally or intravenously; 20 mg/day at 75 years or older) on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression or intolerable adverse events (AEs). The primary end point was objective response rate (ORR). Results Seventy-four patients were enrolled between February 2017 and February 2019. All patients had progressed within 60 days of their last therapy. 74.3% of the patients were resistant to lenalidomide, 31.1% had renal insufficiency and 33.8% had high-risk cytogenetic RRMM. The median follow-up duration was 33.0 months (range 31.1–34.8 months). The ORR was 37.8% in the overall analysis, 32.7% in lenalidomide-refractory patients, 36.0% in patients with high-risk cytogenetics and 34.8% in RRMM patients with renal impairment. The median progression-free survival was 5.7 months (95% CI 3.7–8.8 months). The median overall survival was 24.3 months (95% CI 14.4–41.1 months). The most common grade 3 and 4 treatment-emergent adverse events (TEAEs) were neutropenia (63.5%), leukopenia (37.8%), thrombocytopenia (28.4%), and anemia (31.1%). Pulmonary infection (27.0%) was the most frequent grade 3 and 4 nonhematologic TEAE. No previously unreported AEs were observed. No venous thromboembolism was reported. Conclusions Pomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients. Trial registration The study is registered at Chinese Clinical Trial Registry (ChiCTR) ( ChiCTR-OIC-17013234 , first registered on 03/11/2017).

Abstract Excessive proliferation and migration of airway smooth muscle cell (ASMC) contribute to asthma pathogenesis. Long noncoding RNAs (lncRNAs) are reported to take part in asthma pathogenesis. This study is targeted at deciphering the role of the lncRNA antisense noncoding RNA in the INK4 locus (ANRIL) in ASMC proliferation, migration and extracellular matrix (ECM) deposition. qRT‐PCR was performed to determine ANRIL, miR‐98‐5p, and cyclin D1 (CCND1) mRNA expression levels in transforming growth factor‐β1 (TGF‐β1)‐treated ASMCs. CCK‐8 and Transwell assays were employed to examine ASMC proliferation and migration, respectively. Dual‐luciferase reporter gene assay and RNA immunoprecipitation assay were carried out for analyzing the targeted relationship of miR‐98‐5p with ANRIL or CCND1 mRNA 3′‐UTR. The levels of CCND1 and ECM proteins (such as fibronectin, COL3A1, and COL1A2) in ASMCs were detected through Western blot. In this work, we found that ANRIL and CCND1 were up‐regulated in TGF‐β1‐treated ASMCs, whereas miR‐98‐5p was down‐regulated. ANRIL overexpression facilitated the proliferation, ECM deposition and migration of TGF‐β1‐induced ASMCs, while knocking down ANRIL had the opposite effect. Furthermore, ANRIL targeted miR‐98‐5p directly, and CCND1 was miR‐98‐5p's downstream target. ANRIL indirectly increased CCND1 expression in ASMCs via competitively binding to miR‐98‐5p. MiR‐98‐5p inhibition or CCND1 overexpression counteracted the inhibiting effect that ANRIL knockdown had on TGF‐β1‐stimulated ASMC proliferation, migration and ECM deposition. In conclusion, ANRIL indirectly up‐regulates CCND1 expression by targeting miR‐98‐5p to promote ASMC proliferation, migration and ECM deposition, thus facilitating the pathogenesis of asthma.

Abstract Objective To evaluate how spontaneous breathing trial (SBT) affects successful extubation and prognosis in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients under mechanical ventilation. Methods AECOPD patients under invasive mechanical ventilation were recruited into the study and divided into the SBT and non-SBT groups. SBT patients received SBT for 60 min before extubation, while non-SBT patients that met weaning criteria were immediately extubated without SBT. Results A total of 64 patients were enrolled in analysis, including 32 in SBT group and 32 in non-SBT group. Patients in the two groups had similar baseline demographics and clinical characteristics (all parameters: p = > 0.05). Four (12.5%) patients in the SBT group and 5 (15.6%) in the non-SBT group were reintubated in 48 h of extubation (p = 0.821). During the 28-day follow-up after extubation, 3 patients died, 1 (3.1%) in the SBT group and 2 (6.3%) in the non-SBT group (p = 0.554). Conclusion Our findings indicate that SBT did not affect extubation success, in-hospital mortality, and 28-day survival in AECOPD patients under mechanical ventilation.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory malignancies and has a poor prognosis. In recent years, increasing evidence has shown that an imbalance of metabolism may contribute to unrestricted pancreatic tumour progression and that the pentose phosphate pathway (PPP) plays a pivotal role in cellular metabolism. S100A11 has been shown to regulate multiple biological functions related to the progression and metastasis of various cancer types. However, the exact mechanisms and prognostic value of S100A11 in PDAC remain unclear. Here, we found that S100A11 expression was increased in PDAC and significantly associated with worse prognosis and disease progression. Mechanistically, S100A11 knockdown suppressed the PPP by impairing nascent mRNA synthesis of TKT (transketolase). The current study also demonstrated that H3K4me3 at the −268/+77 region of the TKT promoter was required for its transcriptional activation and S100A11 promoted H3K4me3 loading to the TKT promoter by interacting with SMYD3 protein. Taking these findings together, this study provided new insights into the potential value of S100A11 for treating pancreatic cancer, suggesting that it could be a therapeutic target for PDAC patients.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic hypoxia, inflammation, oxidative stress, and irreversible airflow limitations. Rhodiola L. is a genus of botanical drugs used in traditional medicine that may influence COPD.Objective: A systematic review of the safety and efficacy of Rhodiola L. in patients with COPD.Material and methods: We searched the PubMed, Embase, Cochrane Library, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), Chongqing VIP, Wanfang, and SinoMed databases. The search strategy used terms including “COPD” and “Rhodiola.” Two independent reviewers conducted the literature screening, data extraction, and risk of bias assessment, with a third reviewer involved to resolve disagreements. Statistical analysis was conducted in Review Manager (version 5.4.1), following the Cochrane Handbook.Results: This review included nine studies, of which two focused on Rhodiola crenulata (Hook.f. and Thomson) H. Ohba (R. crenulata) and two on Rhodiola kirilowii (Regel) Maxim (R. kirilowii); the remaining five focused on Rhodiola wallichiana (Hook.) S.H.Fu (R. wallichiana). Compared with the placebo, patients who received Rhodiola L. presented no more adverse events (p = 0.65) but showed significant improvement in the percentage of forced expiratory volume in 1 s at prediction (FEV1%pred), forced expiratory volume in 1 s (FEV1), the ratio of forced expiratory volume in 1 s on forced vital capacity (FEV1/FVC), saturation of oxygen in arterial blood, partial pressure of oxygen in arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood (PaCO2), systolic pulmonary arterial pressure, diastolic pulmonary arterial pressure, COPD assessment test, efficient rate, C-reactive protein, and N-terminal pro-B-type natriuretic peptide (all p < 0.01). Compared with ambroxol, R. kirilowii provided additional benefits to patients with COPD in FEV1%pred, FEV1, FEV1/FVC, PaO2, PaCO2, 8-iso-prostaglandin F2α, superoxide dismutase, glutathione, malondialdehyde, and total antioxidant capacity (all p < 0.01).Conclusion: Among the Rhodiola L. genus, this review included R. wallichiana, R. crenulata, and R. kirilowii, which might be safe and effective in COPD. Although this study has several limitations, further RCTs are needed.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/ display_record.php?RecordID=302881], identifier [CRD42022361890].

Low temperatures restrict the growth and geographic distribution of plants, as well as crop yields. Appropriate transcriptional regulation is critical for cold acclimation in plants. In this study, we found that the mutation of Leaf and flower related (LFR), a component of SWI/SNF chromatin remodeling complex (CRC) important for transcriptional regulation in Arabidopsis (Arabidopsis thaliana), resulted in hypersensitivity to freezing stress in plants with or without cold acclimation, and this defect was successfully complemented by LFR. The expression levels of CBFs and COR genes in cold-treated lfr-1 mutant plants were lower than those in wild-type plants. Furthermore, LFR was found to interact directly with ICE1 in yeast and plants. Consistent with this, LFR was able to directly bind to the promoter region of CBF3, a direct target of ICE1. LFR was also able to bind to ICE1 chromatin and was required for ICE1 transcription. Together, these results demonstrate that LFR interacts directly with ICE1 and activates ICE1 and CBF3 gene expression in response to cold stress. Our work enhances our understanding of the epigenetic regulation of cold responses in plants.

Background: Monkeypox, a zoonotic disease caused by an Orthopoxvirus, presents an etiology similar to smallpox in humans. Currently, there are no licensed treatments for human monkeypox, so clear and urgent research on its prophylaxis and treatment is needed.Objective: The purpose of this study was to explore the evidence of Chinese medicine for contagious pox-like viral diseases and provide suggestions for the multi-country outbreak management of monkeypox.Methods: The review was registered on INPLASY (INPLASY202270013). Ancient classics in China and clinical trials involving randomized controlled trials , non-RCTs, and comparative observational studies of CM on the prevention and treatment of monkeypox, smallpox, measles, varicella, and rubella were retrieved from the Chinese Medical Code (fifth edition), Database of China Ancient Medicine, PubMed, the Cochrane Library, China National Knowledge Infrastructure, Chongqing VIP, Wanfang, Google Scholar, International Clinical Trial Registry Platform, and Chinese Clinical Trial Registry until 6 July 2022. Both quantitative and qualitative methods were applied to present the data collected.Results: The use of CM to control contagious pox-like viral diseases was traced back to ancient Chinese practice cited in Huangdi’s Internal Classic, where the pathogen was recorded nearly two thousand years back. There were 85 articles (36 RCTs, eight non-RCTs, one cohort study, and 40 case series) that met the inclusion criteria, of which 39 studies were for measles, 38 for varicella, and eight for rubella. Compared with Western medicine for contagious pox-like viral diseases, CM combined with Western medicine showed significant improvements in fever clearance time (mean difference, −1.42 days; 95% CI, −1.89 to −0.95; 10 RCTs), rash/pox extinction time (MD, −1.71 days; 95% CI, −2.65 to −0.76; six RCTs), and rash/pox scab time (MD, −1.57 days; 95% CI, −1.94 to −1.19; five RCTs). When compared with Western medicine, CM alone could reduce the time of rash/pox extinction and fever clearance. Chinese herbal formulas, including modified Yinqiao powder, modified Xijiao Dihaung decoction, modified Qingjie Toubiao decoction, and modified Shengma Gegen decoction, were frequently applied to treat pox-like viral diseases and also showed significant effects in shortening the time of fever clearance, rash/pox extinction, and rash/pox scabs. Compared with Western medicine (placental globulin) or no intervention, eight non-randomized trials and observational studies on the prevention of contagious pox-like viral diseases showed a significant preventive effect of Leiji powder among high-risk populations.Conclusion: Based on historical records and clinical studies of CM in managing contagious pox-like viral diseases, some botanical drugs could be an alternative approach for treating and preventing human monkeypox. Prospective, rigorous clinical trials are urgently needed to confirm the potential preventive and treatment effect of Chinese herbal formulas.Systematic Review Registration: [https://inplasy.com/], identifier [INPLASY202270013].

Kai-Xin-San (KXS) is a Chinese medicine formulation that is commonly used to treat depression caused by dual deficiencies in the heart and spleen. Recent studies indicated that miRNAs were involved in the pathophysiology of depression. However, there have been few studies on the mechanism underlying the miRNAs directly mediating antidepressant at clinical level, especially in nature drugs and TCM compound. In this study, we identified circulating miRNAs defferentially expressed among the depression patients (DPs), DPs who underwent 8weeks of KXS treatment and health controls (HCs). A total of 45 miRNAs (17 were up-regulated and 28 were down-regulated) were significantly differentially expressed among three groups. Subsequently, qRT-PCR was used to verify 10 differentially expressed candidate miRNAs in more serum samples, and the results showed that 6 miRNAs (miR-1281, miR-365a-3p, miR-2861, miR-16-5p, miR-1202 and miR-451a) were consistent with the results of microarray. Among them, miR-1281, was the novel dynamically altered and appeared to be specifically related to depression and antidepressant effects of KXS. MicroRNA-gene-pathway-net analysis showed that miR-1281-regulated genes are mostly key nodes in the classical signaling pathway related to depression. Additionally, our data suggest that ADCY1 and DVL1 were the targets of miR-1281. Thus, based on the discovery of miRNA expression profiles in vivo, our findings suggest a new role for miR-1281 related to depression and demonstrated in vitro that KXS may activate cAMP/PKA/ERK/CREB and Wnt/β-catenin signal transduction pathways by down-regulating miR-1281 that targets ADCY1 and DVL1 to achieve its role in neuronal cell protection.

Abstract A solid‐state electrolyte (SSE), which is a solid ionic conductor and electron‐insulating material, is known to play a crucial role in adapting a lithium metal anode to a high‐capacity cathode in a solid‐state battery. Among the various SSEs, the single Li‐ion conductor has advantages in terms of enhancing the ion conductivity, eliminating interfacial side reactions, and broadening the electrochemical window. Covalent organic frameworks (COFs) are optimal platforms for achieving single Li‐ion conduction behavior because of well‐ordered one‐dimensional channels and precise chemical modification features. Herein, we study in depth three types of Li‐carboxylate COFs (denoted LiOOC‐COFn, n = 1, 2, and 3) as single Li‐ion conducting SSEs. Benefiting from well‐ordered directional ion channels, the single Li‐ion conductor LiOOC‐COF3 shows an exceptional ion conductivity of 1.36 × 10−5 S cm−1 at room temperature and a high transference number of 0.91. Moreover, it shows excellent electrochemical performance with long‐term cycling, high‐capacity output, and no dendrites in the quasi‐solid‐state organic battery, with the organic small molecule cyclohexanehexone (C6O6) as the cathode and the Li metal as the anode, and enables effectively avoiding dissolution of the organic electrode by the liquid electrolyte.

Background and AimsResearch on the effect of the coronavirus disease 2019 (COVID-19) pandemic on psychosocial function in patients with pediatric-onset inflammatory bowel disease (PIBD) is limited. This study aimed to evaluate the psychological status of patients with PIBD before and during the pandemic, and the relationship between mental health and disease activity.MethodsThis study was a retrospective cohort study. Statistical analyses were performed to assess the relationship between demographic, clinical data and psychological data (questionnaires) of PIBD patients before and during the epidemic. The anxiety and depression emotional status of the guardians during the pandemic were evaluated.ResultsIn the PIBD follow-up cohort, 42 patients(male 61.9%) were included. Female with PIBD had lower pediatric quality of life inventory(PedsQL) scores (P = 0.007) and higher spence children's anxiety scale(SCAS) scores (P = 0.038) than male. The pandemic did not have a substantial impact on PedsQL, pittsburgh sleep quality index(PSQI), SCAS, or children's depression inventory(CDI) in patients with PIBD. The self-rating anxiety scale(SAS) score, anxiety rate, self-rating depression scale(SDS) score, and depression rate of PIBD guardians were significantly higher than those of healthy controls (SAS, P = 0.008; SDS, P = 0.001).ConclusionsFemale children with PIBD were more vulnerable to decreased QOL and increased anxiety than male children. The anxiety and depression status of PIBD guardians were significantly higher than those of healthy controls during the COVID-19 pandemic. But the COVID-19 pandemic did not significantly affect quality of life(QOL), sleep, anxiety, or depressive mood of patients with PIBD in our study.

Cytokines play vital roles in the pathogenesis of inflammatory bowel disease. IL17B is protective in the development of colitis. However, how IL17B regulates intestinal inflammation and what cells are regulated by IL17B is still unknown. Here, we aimed to illustrate the IL17B dependent cellular and molecular changes in colon tissue in a mouse colitis model. The results showed that IL17B expression in colon tissues was elevated in inflamed tissues than non-inflamed tissues of IBD patients. Wild type (WT) and Il17b deficient (Il17b-/-) mice were given 2.5% dextran sodium sulfate (DSS) water, and in some case, Il17b-/- mice were treated with recombinant mouse IL17B. IL17B deficiency resulted in severe DSS-induced colitis with exaggerated weight loss, shorter colon length, and elevated proinflammatory cytokines in colon. Reconstitution of Il17b-/- mice with recombinant IL17B alleviated the severity of DSS-induced colitis. Single cell transcriptional analyses of CD45+ immune cells in colonic lamina propria revealed that loss of IL17B resulted in an increased neutrophil infiltration and enhanced inflammatory cytokines in intestinal macrophages in colitis, which were confirmed by real-time PCR and flow cytometry. IL17B treatment also inhibited lipopolysaccharide-induced inflammation in bone marrow-derived macrophages and mice. IL17B inhibits colitis by regulating colonic myeloid cell response. It might represent a novel potential therapeutic approach to treat the colitis.

The use of a micro heat sink is an effective means of solving the problem of high-power chip heat dissipation. Diamond/Cu composites exhibit high thermal conductivity and a linear thermal expansion coefficient that is compatible with semiconductor materials, rendering them ideal micro heat sink materials. The aim of this study was to fabricate diamond/Cu and Cu separately as heat sinks and subject them to flow boiling heat transfer experiments. The results indicate that the diamond/Cu heat sink displayed a decrease in wall superheat of 10.2–14.5 °C and an improvement in heat transfer coefficient of 38–51% compared with the Cu heat sink under identical heat fluxes. The heat sink also exhibits enhanced thermal uniformity. Secondary diamond particles are incorporated into the gaps of the main diamonds, thereby constructing a three-dimensional heat conduction network within the composite material. The diamond network enhances the internal heat flux of the material while also creating more nucleation sites on the surface. These increase the boiling intensity of the diamond/Cu heat sink, leading to better heat transfer performance. By combining the transient thermal model with computational fluid dynamics, a heat transfer model based on the diamond/Cu heat sink is proposed. The efficient heat dissipation capability of diamond/Cu heat sinks can lower the working temperature of microelectronic devices, thereby improving device performance and reliability during operation.

Iron (Fe) is necessary for plant growth and development. The mechanism of uptake and translocation in Cadmium (Cd) is similar to iron, which shares iron transporters. Yellow stripe-like transporter (YSL) plays a pivotal role in transporting iron and other metal ions in plants. In this study, MsYSL6 and its promoter were cloned from leguminous forage alfalfa. The transient expression of MsYSL6-GFP indicated that MsYSL6 was localized to the plasma membrane and cytoplasm. The expression of MsYSL6 was induced in alfalfa by iron deficiency and Cd stress, which was further proved by GUS activity driven by the MsYSL6 promoter. To further identify the function of MsYSL6, it was heterologously overexpressed in tobacco. MsYSL6-overexpressed tobacco showed better growth and less oxidative damage than WT under Cd stress. MsYSL6 overexpression elevated Fe and Cd contents and induced a relatively high Fe translocation rate in tobacco under Cd stress. The results suggest that MsYSL6 might have a dual function in the absorption of Fe and Cd, playing a role in the competitive absorption between Fe and Cd. MsYSL6 might be a regulatory factor in plants to counter Cd stress. This study provides a novel gene for application in heavy metal enrichment or phytoremediation and new insights into plant tolerance to toxic metals.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a superfamily of RNA-binding proteins consisting of more than 20 members. These proteins play a crucial role in various biological processes by regulating RNA splicing, transcription, and translation through their binding to RNA. In the context of muscle development and regeneration, hnRNPs are involved in a wide range of regulatory mechanisms, including alternative splicing, transcription regulation, miRNA regulation, and mRNA stability regulation. Recent studies have also suggested a potential association between hnRNPs and muscle-related diseases. In this report, we provide an overview of our current understanding of how hnRNPs regulate RNA metabolism and emphasize the significance of the key members of the hnRNP family in muscle development. Furthermore, we explore the relationship between the hnRNP family and muscle-related diseases.

The Silk Road Economic Belt and the 21st Century Maritime Silk Road Initiative (BRI) proposed in 2013 by China has greatly accelerated the social and economic development of the countries along the Belt and Road (B&R) region. However, the international community has questioned its impact on the ecological environment and a comprehensive assessment of ecosystem quality changes is lacking. Therefore, this study proposes an objective and automatic method to assess ecosystem quality and analyzes the spatiotemporal changes in the B&R region. First, an ecosystem quality index (EQI) is established by integrating the vegetation status derived from three remote sensing ecological parameters including the leaf area index, fractional vegetation cover and gross primary productivity. Then, the EQI values are automatically categorized into five ecosystem quality levels including excellent, good, moderate, low and poor to illustrate their spatiotemporal changes from the years 2016 to 2020. The results indicate that the spatial distributions of the EQIs across the B&R region exhibited similar patterns in the years 2016 and 2020. The regions with excellent levels accounted for the lowest proportion of less than 12%, while regions with moderate, low and poor levels accounted for more than 68% of the study area. Moreover, based on the EQI pattern analysis between the years 2016 and 2020, the regions with no significant EQI change accounted for up to 99.33% and approximately 0.45% experienced a significantly decreased EQI. Therefore, this study indicates that the ecosystem quality of the B&R region was relatively poor and experienced no significant change in the five years after the implementation of the “Vision and Action to Promote the Joint Construction of the Silk Road Economic Belt and the 21st Century Maritime Silk Road”. This study can provide useful information for decision support on the future ecological environment management and sustainable development of the B&R region.

Although aluminum alloys are widely used in the automotive and aerospace industries due to their excellent strength-to-weight ratio and good corrosion resistance, the poor tribological performance and low compatibility of these materials with lubricant anti-wear and anti-friction additives in conventional mineral oils are major limitations. In addition, environmental awareness has increased the need for more environmentally friendly lubricants. Ionic Liquids (ILs) have exhibited significant potential as lubricants and lubricant additives. One of the more interesting properties of ILs is that they can form physically-adsorbed or chemically-reacted layers that reduce friction and wear of the surfaces in contact. Among ILs, Protic Ionic Liquids (PILs) have received more attention recently because of their simple and economic synthesis route. Furthermore, the anions and cations of PILs can be selected to be considered environmentally benign. In this article, the tribological behavior of a family of six PILs are studied as additives to a biodegradable oil (BO), under aluminum-steel contact. Al2024 disks slid against AISI52100 steel balls under a normal load of 3 N and a frequency of 5 Hz at room temperature and using a ball-on-flat reciprocating tribometer. PILs used in this study, were synthesized using two strong acids, with short and long hydrocarbon chains, and three weak bases with different propensities to hydrogen bonds. Results show that, although adding just 1 wt.% of any PIL to BO reduced friction and wear, the alkyl chain length influenced the lubricating ability of these ordered fluids. Wear mechanisms and surface interaction are discussed on the basis of 3D profilometry, SEM-EDX and RAMAN spectroscopy.