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Pulmonary fibrosis poses a significant health threat with very limited therapeutic options available. In this study, we reported the enhanced expression of mesenchymal homobox 1 (MEOX1) in pulmonary fibrosis patients, especially in their fibroblasts and endothelial cells, and confirmed MEOX1 as a central orchestrator in the activation of profibrotic genes. By high-throughput screening, we identified Ailanthone (AIL) from a natural compound library as the first small molecule capable of directly targeting and suppressing MEOX1. AIL demonstrated the ability to inhibit both the activation of fibroblasts and endothelial-to-mesenchymal transition of endothelial cells when challenged by transforming growth factor-β1 (TGF-β1). In an animal model of bleomycin-induced pulmonary fibrosis, AIL effectively mitigated the fibrotic process and restored respiratory functions. Mechanistically, AIL acted as a suppressor of MEOX1 by disrupting the interaction between the transcription factor JUN and the promoter of MEOX1, thereby inhibiting MEOX1 expression and activity. In summary, our findings pinpointed MEOX1 as a cell-specific and clinically translatable target in fibrosis. Moreover, we demonstrated the potent anti-fibrotic effect of AIL in pulmonary fibrosis, specifically through the suppression of JUN-dependent MEOX1 activation.

The silicon-rich MoSi2 coating with a submicron surface roughness is deposited on Mo substrate by the hot-dip silicon (HDS) plating process. The microstructure, phase composition, and growth mechanism of the silicon-rich MoSi2 coating are characterized. The oxidation kinetics and oxidation mechanism of the coated samples and bare Mo at 1200 °C are also analyzed and compared. The results indicate that the silicon-rich MoSi2 coating is comprised of Si outermost layer, MoSi2 intermediate layer and Mo5Si3 interface layer. The coating has a high surface silicon concentration and a dense structure, and the average surface roughness (RSa) is only 0.248 μm. After exposed at 1200 °C for 20 h, the per unit area weight change rate (Mc) of the coating is only 0.183 mg/cm2 and the thickness of oxide layer is 6.72 μm. The smooth surface, compact structure and excellent self-healing ability of the silicon-rich coating ensure its outstanding antioxidant.

Abstract Recent technological breakthroughs in single-particle cryo-electron microscopy (cryo-EM) enable rapid atomic structure determination of biological macromolecules. A major bottleneck in the current single particle cryo-EM pipeline is the preparation of good quality frozen cryo-EM grids, which is mostly a trial-and-error process. Among many issues, preferred particle orientation and sample damage by air–water interface (AWI) are common practical problems. Here we report a method of applying metallo-supramolecular branched polymer (MSBP) in the cryo-sample preparation for high-resolution single-particle cryo-EM. Our data shows that MSBP keeps a majority of particles away from air–water interface and mitigates preferred orientation as verified by the analyses of apoferritin, hemagglutinin) trimer and various sample proteins. The use of MSBP is a simple method to improve particle distribution for high-resolution structure determination in single-particle cryo-EM.

The Al-rich hot-dip aluminum composite coatings were synthesized on Mo surface by hot-dip aluminizing under different deposition processes. The aluminide coatings present a very smooth dense coating structure with a lower surface roughness and fine grain size, the average surface roughness (RSa) values are only 0.118–0.869 μm, and the corresponding surface area growth rate (Sdr) values are 3.85–80.19 %. Increasing the deposition temperature is beneficial for the transition of low melting point compounds of the coating surface to high melting point compounds, and extending the hot dip time is profit for the diffusion and enrichment of Al atoms on the coating surface. Besides, increasing the deposition temperature or time can also promote the growth of Al4Mo grains, thereby significantly increasing the coating thickness. When the deposition temperature is 750 °C, the thicknesses of Al4Mo and Al8Mo3 layers increases in a parabolic law with deposition time, and the Kp values both of them are 3.46 × 10−13 m2/s and 1.47 × 10−15 m2/s, respectively. The growth of the coating depends on the continuous diffusion of Al atoms towards the substrate direction, and the difference in chemical potential between Al atoms in each phase is the main driving force for coating growth.

Abstract The TMEM63 family proteins (A, B, and C), calcium-permeable channels in animals that are preferentially activated by hypo-osmolality, have been implicated in various physiological functions. Deficiency of these channels would cause many diseases including hearing loss. However, their structures and physiological roles are not yet well understood. In this study, we determine the cryo-electron microscopy (cryo-EM) structure of the mouse TMEM63C at 3.56 Å, and revealed structural differences compared to TMEM63A, TMEM63B, and the plant orthologues OSCAs. Further structural guided mutagenesis and calcium imaging demonstrated the important roles of the coupling of TM0 and TM6 in channel activity. Additionally, we confirm that TMEM63C exists primarily as a monomer under physiological conditions, in contrast, TMEM63B is a mix of monomer and dimer in cells, suggesting that oligomerization is a regulatory mechanism for TMEM63 proteins.

Abstract Chemotherapy-induced ovarian damage and infertility are significant concerns for women of childbearing age with cancer; however, the underlying mechanisms are still not fully understood. Our study has revealed a close association between epigenetic regulation and cyclophosphamide (CTX)-induced ovarian damage. Specifically, CTX and its active metabolite 4-hydroperoxy cyclophosphamide (4-HC) were found to increase the apoptosis of granulosa cells (GCs) by reducing EZH2 and H3K27me3 levels, both in vivo and in vitro. Furthermore, RNA-seq and CUT&Tag analyses revealed that the loss of H3K27me3 peaks on promoters led to the overactivation of genes associated with transcriptional regulation and apoptosis, indicating that stable H3K27me3 status could help to provide a safeguard against CTX-induced ovarian damage. Administration of the H3K27me3-demethylase inhibitor, GSK-J4, prior to CTX treatment could partially mitigate GC apoptosis by reversing the reduction of H3K27me3 and the aberrant upregulation of specific genes involved in transcriptional regulation and apoptosis. GSK-J4 could thus potentially be a protective agent for female fertility when undergoing chemotherapy. The results provide new insights into the mechanisms for chemotherapy injury and future clinical interventions for fertility preservation.

Vanadium titano-magnetite is an important iron ore resource containing iron, vanadium and titanium. Although iron and vanadium can be recovered by the traditional blast furnace process, titanium can only be stored in the form of TiO2 bearing slag, which resulting in a great waste of titanium resources. In the full oxygen bath smelting process, thanks to high oxygen potential, low nitrogen content and no coke bed in the furnace, the reduction of TiO2 in the slag. This may lead to slag viscosity, inhibit the smelting of vanado-titano-magnetite, and obtain a slag with high TiO2 content. Based on slag coexistence theory, a multi system coexistence theoretical model of vanadium titano-magnetite smelting slag is established, and the influence of slag basicity on the concentration of slag components and the ratio of sulfur between slag and iron is calculated. The results show that with the increase of slag basicity, the interaction concentration of TiO2 in slag decreases gradually, which makes the reduction of TiO2 more difficult and is conducive to the smelting of vanadium–titanomagnetite. Under the optimum alkalinity and reduction temperature (R=1.1, melting temperature is 1500 °C), the distribution ratio of S element between slag and iron is 6.57, and the theoretical S concentration in molten iron is 0.073%. The molten iron can meet the steel-making requirements after pretreatment and desulfurization.

Al2O3–Cr2O3 refractories have excellent slag corrosion resistance and can adapt to the oxidation/reduction atmosphere in the smelting reduction ironmaking furnace. Improving the corrosion resistance of chrome corundum refractories is of great significance for extending the life length of industrial kilns and decreasing carbon emissions. In this work, the influences of ZrO2 content on the phase evolution, microstructure, physicochemical properties, mechanical properties and slag corrosion resistance of the ZrO2 reinforced Al2O3–Cr2O3 composite refractories were investigated. The results show that the ZrO2 reinforced Al2O3–Cr2O3 composites are primarily composed of (Al, Cr)2O3 solid solution and m-ZrO2. The compressive strength, flexural strength and hardness of the composite refractories can be improved by adding 2.5 wt% ZrO2. However, adding more ZrO2 will reduce its mechanical properties. This is due to ZrO2 excessive content will augement the porosity of the composite refractories, and the phase transformation of ZrO2 will also lead to the formation of microcracks during the cooling process. It is worth noting that higher ZrO2 content improves the thermal shock resistance of the composites, which is primarily put down to the microcrack toughening mechanism of ZrO2. The corrosion tests show that the thicknesses of the corrosion and infiltration layers of composite refractories are significantly decreased accompanied by ZrO2 content increase. This is because the formation of high melting point CaZr4O9 reduces the CaO content and slag alkalinity, and inhibits the dissolution of Al2O3 into the slag to a certain extent. Therefore, the slag corrosion/penetration resistance of the of the composites are obviously improved with the increase of ZrO2 addition.

This study explores the role of church museums represented by the Tsinanfu Institute in the spread of Christianity in modern China. Established in 1887, Tsinanfu Institute, formerly Tsingchowfu Museum, stands as an early pioneer of church museums in China with the mission of spreading Christianity. It has taken exhibition and knowledge dissemination and social education as its core functions, indirect evangelization and expansion of religious influence as its fundamental purpose, and the Chinese way of localization and the promotion of harmonious relations with the community as its important working guidelines. It has established a new operational concept as a “public cultural museum”, realizing the transformation of the church museum from a missionary venue for the intellectuals to a new type of missionary venue for the general public. The development stages of the church museum operational concept represented by Tsinanfu Institute are mainly socialization, education, localization, and the popularization of higher education, which is a microcosm of the development trend of the Christian Endeavour Movement, Social Gospel, and vernacularization thought. Tsinanfu Institute shows significant research value in studying new missionary concepts and exploring the new way of missionary work in the church during the late 19th and early 20th centuries.

Chromium-containing refractories have excellent high-temperature corrosion resistance. In this work, Cr2O3 reinforced Al2O3–SiO2 composite refractories were prepared by reaction sintering process. The microstructure, phase composition, mechanical properties and strengthening mechanism of the Cr2O3 reinforced Al2O3–SiO2 composite refractories were investigated. The results show that when the Cr2O3 content is 10–20 wt%, the composites are mainly composed of Cr-mullite (Al3.94Cr0.50Si1.56O10.44), (Al, Cr)2O3, and a small amount of SiO2 phase. When the Cr2O3 content exceeds 20%, the composite refractories mainly consist of (Al, Cr)2O3 and SiO2 phases. The appropriate amount of Cr2O3 can effectively enhance the mechanical properties and compactness of the Cr2O3 reinforced Al2O3–SiO2 composites. This is mainly due to the formation of Cr doped mullite and SiO2 phases, which reduces the sintering temperature of mullite ceramics and improves its density and mechanical properties. The highest hardness (27.03 GPa), flexural strength (213.21 MPa) and compressive strength (528 MPa) values are observed at a Cr2O3 content of 20 wt%. However, excessive addition of Cr2O3 will deteriorate the mechanical properties of the composites. The formation of a large amount of (Al, Cr)2O3 solid solution phase will increase the porosity of the composites, and reduce the compactness and sintering properties of the composites.

A Si-rich NbSi2 coating was prepared on Nb substrate by hot dip silicon plating process, which mainly consists of Nb5Si3 interfacial layer, NbSi2 intermediate layer and silicon-rich NbSi2 outer layer. The Si-rich NbSi2 coating has flat surface and dense structure, and the surface roughness is only 0.218–0.548 μm. Raising the deposition temperature can also significantly increase the growth rate of the Si-rich NbSi2 coating. The hot-dip silicon plating process has an extremely low reaction activation energy (249.99 kJ mol−1), which indicates that there are a large number of activated molecules during hot dip silicon plating. The silicon atoms in the molten bath deposited on the Nb surface and maintained a high chemical potential gradient continuously. Therefore, the solid diffusion reaction of Nb–Si was continuous, and the Nb5Si3 phase was generated and consumed continuously, and transformed into NbSi2 phase, which led to a higher growth rate of coating (1.7 × 10−13 to 4.3 × 10−13 m2 s).

Exposure to irreparable stresses induces transient ciliogenesis, enabling communication with PML-NBs via a FBF1 pathway to trigger senescence in mammalian cells. Fbf1 ablation reduces senescence and associated health decline in mice, highlighting cilia as a promising senotherapy target.

Senile osteoporosis (SOP) is a prevalent manifestation of age-related bone disorders, resulting from the dysregulation between osteoblast (OB)-mediated bone formation and osteoclast (OC)-mediated bone resorption, coupled with the escalating burden of cellular senescence. Traditional Chinese medicine (TCM) herbs, renowned for their remarkable attributes encompassing excellent tolerability, low toxicity, heightened efficacy, and minimal adverse reactions, have gained considerable traction in OP treatment. Emerging evidence substantiates the therapeutic benefits of various TCM formulations and their active constituents, including Zuogui wan, Fructus Ligustri Lucidi, and Resveratrol, in targeting cellular senescence to address SOP. However, a comprehensive review focusing on the therapeutic efficacy of TCM against SOP, with a particular emphasis on senescence, is currently lacking. In this review, we illuminate the pivotal involvement of cellular senescence in SOP and present a comprehensive exploration of TCM formulations and their active ingredients derived from TCM, delineating their potential in SOP treatment through their anti-senescence properties. Notably, we highlight their profound effects on distinct aging models that simulate SOP and various senescence characteristics. Finally, we provide a forward-looking discussion on utilizing TCM as a strategy for targeting cellular senescence and advancing SOP treatment. Our objective is to contribute to the unveiling of safer and more efficacious therapeutic agents for managing SOP.

Abstract Aim To compare the prognostic value of tumor-infiltrating lymphocytes (TILs) and CD3 + cells and CD20 + cells between schistosomal colorectal cancer (SCRC) and non-schistosomal CRC (NSCRC). Background Although schistosomiasis has been basically eliminated, it has not been completely extinction in China, and occasional outbreaks occur in Europe recently. The role of immune cells in the immune microenvironment of SCRC and NSCRC is remaining obscure, and the inflammation-based prognostic systems of SCRC has rarely been reported. Methods HE-stained sections of 349 colorectal cancer (CRC) tumors, which were completely resected, were evaluated for density of TILs. Meanwhile, we evaluated CD3 + T lymphocytes and CD20 + B lymphocytes by immunochemistry. The relationship of these infiltrating immune cells with clinicopathological features, including schistosomiasis, and clinical outcomes was evaluated, and the prognostic roles of TILs in SCRC and NSCRC were explored. Results Except for age (P 0.05). Beside, the positive expression pattern of sTILs, iTILs, CD3, and CD20 between NSCRC and SCRC patients was also similar (P > 0.05). In the whole cohort, sTILs and CD3 were defined as independent prognostic factors (P = 0.031 and P = 0.003, respectively). CD3 was an independent prognostic factor both in the NSCRC and SCRC set (P = 0.026 and P = 0.045, respectively). Higher sTILs, CD3, and CD20 were correlated with less aggressive tumor characteristics in the whole cohort and in subgroups. Conclusion Although CD3 was an independent prognostic factor for both NSCRC and SCRC set, there were no significant differences between SCRC and NSCRC patients in sTILs, CD3, CD20, and in other clinicopathological features.

The current stereo warehouse in the cold chain logistics industry faces problems such as high product loss rate, severe temperature deviations, and low level of informatization. To ensure the food quality and safety of cold chain logistics warehouses, and achieve cost reduction and efficiency improvement, this study focuses on the operational scenarios of stereo warehouses in cold chain logistics, and designs a five-dimensional digital twin model with full mapping and multidimensional simulation. By integrating heterogeneous data from multiple sources, it achieves real-time visualization and monitoring of all elements in warehouses, and proposes a model optimization strategy that supports system-linked decision-making. This strategy intelligently adjusts the load and thermal distribution in the temperature-controlled zones of warehouses to maximize operational efficiency and reduce operating costs. Using this approach, a digital twin system for cold chain logistics warehouses was constructed. By comparing the warehouse operation data before and after optimization, the loss rate of fresh vegetables under the same storage conditions was reduced by 25-30%. This system achieves precise mapping and coordinated operation of real-time data from cold chain logistics warehouses and dynamic virtual models. The practical application of this solution is demonstrated in a cold-chain warehouse of a supply chain company in Guangdong, forming an integrated control model for cold chain logistics warehouses. This model provides a reference for the application of digital twin technology in the operation, scheduling, decision-making, and collaborative operations of cold chain logistics warehouses and offers new possibilities for establishing improved packaging for perishable products and ensuring cold chain food quality and safety.

Seahorses may have required adaptations to avoid immunological rejection of allogenic embryos by males. The authors show that a single substitution in tlx1 is associated with loss of the spleen in seahorses, and that across the clade, degree of male pregnancy is negatively correlated with immune gene repertoire complexity.

Summary: Cochlear and vestibular hair cells are highly specialized sensory receptors for hearing and balance. Here, we report a serendipitous identification of a hair-cell-specific organelle in neonatal mouse inner ear, which we name “apicosome.” The apicosome is ∼500 nm in diameter and shows itinerant nature and transient appearance during development in cochlear hair cells. In contrast to cochlear hair cells, the apicosome persists in vestibular hair cells even in adult. The timing of apicosome translocation and disappearance in cochlear hair cells during development is correlated with kinocilium development and maintenance. The apicosome is not seen in supporting cells despite the fact that nascent supporting cells have microvilli and a primary cilium. Interestingly, transdifferentiated hair cells from supporting cells also contain apicosome, suggesting that it is unique to hair cells. Thus, our study identifies a previously undescribed organelle in hair cells and lays the foundation for further characterization of this specialized structure.

Abstract Aims The best revascularization strategy for patients with ischaemic heart failure (IHF) remains unclear. Current evidence and guidelines mainly focus on patients with severe ischaemic heart failure (ejection fraction [EF]

Colorectal cancer (CRC) is the third most common malignant tumor in the world. CRC has high morbidity and mortality rates and it is a serious threat to human health. Ferroptosis is a unique form of iron-dependent oxidative cell death that is usually accompanied by iron accumulation and lipid peroxidation. Ferroptosis has attracted worldwide attention since it was first proposed. It plays an important role in the development of a variety of diseases, such as tumors, ischemia/reperfusion injury, nervous system diseases, and kidney damage, and it may serve as a new therapeutic target. This article reviews the mechanism of ferroptosis and the possibility to target ferroptosis pathways in CRC, providing new ideas for the diagnosis and treatment of CRC.

Abstract Background The effect of schistosomiasis on CD8+ T cells and then on PD-L1 expression was unknown, and the utility of CD8+ TILs as a biomarker for schistosomal-associated colorectal cancer (SCRC) rarely has been reported. Methods Three hundred thirty-eight patients with colorectal cancer (CRC) were enrolled. Immunohistochemical analysis was conducted to evaluate the expression of PD-L1 and the infiltration of CD8+ T cells. Results In the total cohort, the results showed that CD8+ TIL density was positively correlated with tumoral (p = 0.0001) and stromal PD-L1 expression (p = 0.0102). But there were no correlation between schistosomiasis and CD8+ TILs and PD-L1. Furthermore, CD8+ TIL density (p = 0.010), schistosomiasis (p = 0.042) were independent predictive factors for overall survival (OS). Stromal PD-L1 (sPD-L1) was correlated with OS (p = 0.046), but it was not an independent predictor. In patients without schistosomiasis, CD8 + T cells (p = 0.002) and sPD-L1 (p = 0.005) were associated with better OS. In patients with schistosomiasis, CD8 + T cells were independent prognosis factor (p = 0.045). Conclusions The study showed that CD8+ TILs was an independent predictive factor for OS in CRC and SCRC patients. The expression of PD-L1 was positively associated with CD8 + TILs density. There were no correlation between schistosomiasis and CD8 + TILs and PD-L1. Stromal PD-L1 but not tPD-L1 was significantly associated with OS, whereas it was not an independent prognostic factor.

In recent years, numerous studies have demonstrated that the tumor immune microenvironment (TIME) is capable of regulating the growth of tumors, and tumor-infiltrating immune cells in the TIME can affect the prognosis and treatment responses of patients. Consequently, therapies targeting these immune cells have emerged as important antitumor treatments. As a crucial componet of the perioperative treatment of malignant tumors, neoadjuvant chemotherapy (NACT) can improve the surgical resection rate and prognosis of patients and is a suitable clinical model to evaluate the effect of chemotherapy on the TIME. To provide a rationale for developing valid combinational therapies, this review summarizes the impact of NACT on the TIME, the relationship between tumor-infiltrating immune cells and treatment responses of patients, and the prognostic value of these infiltrating immune cells.

BackgroundN7-methylguanosine (m7G), one of the most common post-transcriptional modifications, can be present in tRNA, mRNA, and miRNA to mediate the progression of various tumors. However, the possible role of m7G in gastric cancer (GC) is still unknown.Materials and MethodsIn this study, SNVs (single nucleotide variations), CNVs (copy number variations), and methylation of m7G-related genes (m7GRGs) were analyzed. The relationship between them and the expression of m7GRGs and prognosis of GC patients was explored. Based on 13 prognostic-related m7GRGs, 567 GC samples were classified into three subtypes using the ConsensusClusterPlus package. we compared survival status, clinical traits, immune cell infiltration, immune checkpoints, tumor microenvironment (TME), tumor immune dysfunction and exclusion (TIDE), and potential biological pathways among the three subtypes. Then, patients were again grouped into different genetic subtypes based on the DEGs among the three subtypes. In addition, a prognostic m7GRG_Score was constructed using five risk genes applicable to patients of any age, gender and stage. We also assessed tumor mutational burden (TMB), microsatellite instability (MSI), cancer stem cell (CSC) index, sensitivity of antineoplastic drugs, efficacy of anti-PD-1 and anti-CTLA4 immunotherapy between high and low m7GRG_Score groups. Finally, we established a nomogram based on m7GRG_Score and tumor stage to enhance the clinical application of the model. miRNAs and lncRNAs that could regulate expression of risk genes were searched.ResultsSNVs, CNVs, and methylation of m7GRGs were associated with m7GRGs expression. However, they did not significantly affect the survival of GC patients. Our results also confirmed that patients in subtypes B and C and low m7GRG_Score groups had longer survival time, better clinical stage, more immune cell infiltration, fewer immune escape and dysfunction compared to subtype A and high m7GRG_Score groups. A low m7GRG_score was featured with increased microsatellite instability-high (MSI-H), TMB, and efficacy of immunotherapy.ConclusionThe m7GRG_Score model may become a beneficial tool for predicting prognosis and guiding personalized treatment in GC patients. These findings will improve our knowledge of m7G in GC and provide new methods for more effective treatment strategies.

Abstract Insulin resistance (IR) plays an important role in the development of hypertension. Triglyceride and glucose index (TyG index), and triglyceride to high‐density lipoprotein cholesterol ratio (TG/HDL‐c) as effective IR surrogate indexes have been verified in numerous studies. Therefore, the authors conducted a large cross‐sectional study to explore the association of TyG index and TG/HDL‐c with prehypertension and hypertension in the same normoglycemic subjects from Tianjin, China. A total of 32 124 adults were eligible for this study. According to the level of blood pressure, the enrolled individuals were divided into three groups, which were normotension, prehypertension, and hypertension. In multiple logistic regression analysis, there was associated with prehypertension and hypertension when comparing the highest TyG index to the lowest TyG index and corresponding ORs were 1.795 (1.638, 1.968) and 2.439 (2.205, 2.698), respectively. For TG/HDL‐c, the corresponding ORs were 1.514 (1.382, 1.658) and 1.934 (1.751, 2.137), respectively. Furthermore, when comparing the fourth quartile to the first quartile of TyG index and TG/HDL‐c, respectively, both corresponding ORs of hypertension were higher than prehypertension. Elevated TyG index and TG/HDL‐c levels were associated with prehypertension and hypertension in normoglycemic individuals. Moreover, the TyG index was more significant than TG/HDL‐c in distinguishing hypertension. They have the potential to become cost‐effective monitors in the hierarchical management of prehypertension and hypertension.

In this study, we aimed to reveal the association between circRNA-related single nucleotide polymorphisms (SNPs) with the susceptibility of silicosis. To achieve this goal, a silicosis-related GWAS was constructed to select the candidate SNPs, and circBase database was utilized to select the promising SNPs which may locate on circRNAs. In addition, the eQTL analysis between the SNPs and located genes was performed to select the candidate SNPs. Finally, the association between candidate SNPs with the susceptibility of silicosis was validated. As a result, we firstly selected 10,922 SNPs with P

Population aging has become an issue that the world should to face together. Public spaces in urban areas play an important role in stimulating social interactions for the elderly, especially close social interactions. Although a volume of studies have focused on the health of the elderly and the shaping of urban space, they have neglected the need for close social behavior of the elderly group. This analysis addresses the question: What are the principles to improve public space qualities which facilitate age-friendly social interactions for the elderly? Blind-dating activities in Beijing City work as an example of close social interactions between the elderly. Methods include a case study in Beijing, field survey, and Space Syntax with related tools. The survey took place from 1 July to 30 September 2022. Around 102 elderly men and 84 women aging from 55 to 75 participated in the survey process. Results indicate that the close social interaction can positively comfort the elderly’s physical and psychological situations. It could be a path for the single elderly group meet a partner, make new friends, and establish new social networks. Consequently, three principles, including obtaining the safety of public space, keeping greenery in the social environment, and providing suitable space for close social interactions are proposed towards age-friendly urban areas. These support the regeneration of the elderly’s social life and stimulate a chasing of happy later lives.

Existing studies reported that some circular RNAs (circRNAs) play vital roles in the development of pulmonary fibrosis. However, few studies explored the biomarker potential of circRNAs for pulmonary fibrosis based on population data. Therefore, we aimed to identify peripheral blood circRNAs as potential biomarkers for diagnosing silicosis and idiopathic pulmonary fibrosis (IPF). In brief, an RNA-seq screening based on 4 silicosis cases and 4 controls was initially performed. Differentially expressed circRNAs were combined with the human serum circRNA dataset to identify overlapping serum-detectable circRNAs, followed by validation using the GEO dataset (3 IPF cases and 3 controls) and subsequent qRT-PCR, including 84 additional individuals. Following the above steps, 243 differentially expressed circRNAs were identified during the screening stage, with fold changes ≥ 1.5 and P

Cancer cells, as well as surrounding stromal and inflammatory cells, form an inflammatory tumor microenvironment (TME) to promote all stages of carcinogenesis. As an emerging post-translational modification (PTM) of serine and threonine residues of proteins, O-linked-N-Acetylglucosaminylation (O-GlcNAcylation) regulates diverse cancer-relevant processes, such as signal transduction, transcription, cell division, metabolism and cytoskeletal regulation. Recent studies suggest that O-GlcNAcylation regulates the development, maturation and functions of immune cells. However, the role of protein O-GlcNAcylation in cancer-associated inflammation has been less explored. This review summarizes the current understanding of the influence of protein O-GlcNAcylation on cancer-associated inflammation and the mechanisms whereby O-GlcNAc-mediated inflammation regulates tumor progression. This will provide a theoretical basis for further development of anti-cancer therapies.

Pentameric ligand-gated ion channels (pLGICs) are key players in neurotransmission and have been shown to be modulated by the lipid environment, however the underlying mechanism is not well understood. Here, the authors report structures of the pLGIC 5-HT3A serotonin receptor reconstituted into lipid bilayer discs and reveal lipid–protein interactions as well as asymmetric activation of the homopentameric receptor.

Abstract Background To assess the effects of proprotein convertase subtilisin/kexin type 9 inhibitor (evolocumab) on lipoprotein particles subfractions with Nuclear Magnetic Resonance spectroscopy in patients with acute coronary syndromes. Methods A total of 99 consecutive patients with ACS were enrolled and assigned to either the experimental group (n = 54) or the control group (n = 45). The combination therapy of PCSK9 inhibitor (Repatha®, 140 mg, q2w) and moderate statin (Rosuvastatin, 10 mg, qn) was administered in the experimental group, with statin monotherapy (Rosuvastatin, 10 mg, qn) in the control group. The therapeutic effects on lipoprotein particle subfractions were assessed with NMR spectroscopy after 8 weeks treatment, and the achievement of LDL-C therapeutic target in both groups were analyzed. Results In the experimental group, after 8 weeks of evolocumab combination treatment, the concentrations of blood lipids (TC, LDL-C and its subfractions [LDL-1 to 6], VLDL-C and its subfractions [VLDL-1 to 5], IDL-C, and HDL-C), lipoprotein particles, and their subfractions [VLDL-P, IDL-P, LDL-P, and its subfractions [LDL-P1 to 6], apoB, and LP(a)] demonstrated therapeutic benefits with statistical significance (P

Abstract Background To analyze the risk factors for hypertension in different age groups of urban and rural residents in Tianjin. Methods A total of 33,997 people (35–75 years old) from 13 community health service centers and primary hospitals in Tianjin participated in this study. They were divided into the youth group (≤ 40 years old), middle-aged group (41–65 years old), and elderly group (> 65 years old). Then, a questionnaire survey was administered, followed by physical and blood biochemical examinations. The demographic characteristics and prevalence were recorded and counted. Subsequently, risk factors were analyzed using univariate and stepwise multivariate logistic regression analysis. Results In the youth, middle-aged, and elderly groups, the prevalence rate of hypertension was 18.65, 51.80, and 76.61%, respectively. Logistic regression analysis showed that obesity(OR: 3.263, 95% CI: 1.039–1.656), men (OR: 2.117, 95% CI: 1.691–2.651), diabetes (OR: 1.978, 95% CI: 1.398–2.799), high triglycerides(OR 1.968 95% CI: 1.590–2.434) and family history of stroke (OR: 1.936, 95% CI: 1.287–2.911) are the five factors in youth. In middle-aged group, the significantly associating factors were obesity (OR: 2.478, 95% CI: 2.330–2.636), diabetes (OR: 2.173, 95% CI: 1.398–2.799), family history of stroke (OR: 1.808, 95% CI: 1.619–2.020), maleness (OR: 1.507, 95% CI: 1.412–1.609),Hypertriglyceridemia (OR 1.490 95% CI: 1.409–1.577),family history of cardiovascular disease (OR: 1.484, 95% CI: 1.307–1.684),Hypercholesterolemia (OR 1.228 95% CI: 1.160–1.299). In the elderly group, obesity (OR: 2.104, 95% CI: 1.830–2.418), family history of strokes (OR: 1.688, 95% CI: 1.243–2.292), diabetes mellitus (OR: 1.544, 95% CI: 1.345–1.773), family history of cardiovascular disease (OR: 1.470, 95% CI: 1.061–2.036), hypertriglyceridemia (OR: 1.348, 95% CI: 1.192–1.524) increased the risk for hypertension. Waist circumference (WC) and waist-to-height ratio (WHtR) increased with age, and the value of these two measures for predicting hypertension was better than BMI in middle-aged group. Conclusion Obesity is the most important risk factor for hypertension in all age groups. Diabetes, family history of strokes and high triglyceride were also significant risk factors for all age groups. There was a gender difference between the young and middle-aged groups, with men more likely to hypertension. Waist circumference (WC) and waist-to-height ratio (WHtR) were better predictors of hypertension than BMI in middle-aged group.

Abstract Gastric cancer (GC) is a leading cause of cancer-induced mortality, with poor prognosis with metastasis. The mechanism of gastric carcinoma lymph node metastasis remains unknown due to traditional bulk-leveled approaches masking the roles of subpopulations. To answer questions concerning metastasis from the gastric carcinoma intratumoural perspective, we performed single-cell level analysis on three gastric cancer patients with primary cancer and paired metastatic lymph node cancer tissues using single-cell RNA-seq (scRNA-seq). The results showed distinct carcinoma profiles from each patient, and diverse microenvironmental subsets were shared across different patients. Clustering data showed significant intratumoural heterogeneity. The results also revealed a subgroup of cells bridging the metastatic group and primary group, implying the transition state of cancer during the metastatic process. In the present study, we obtained a more comprehensive picture of gastric cancer lymph node metastasis, and we discovered some GC lymph node metastasis marker genes (ERBB2, CLDN11 and CDK12), as well as potential gastric cancer evolution-driving genes (FOS and JUN), which provide a basis for the treatment of GC.

Background: The role of liquid–liquid phase separation (LLPS) in cancer has also attracted more and more attention, which is found to affect transcriptional regulation, maintaining genomic stability and signal transduction, and contribute to the occurrence and progression of tumors. However, the role of LLPS in digestive system tumors is still largely unknown.Results: Here, we characterized the expression profiles of LLPS regulators in 3 digestive tract tumor types such as COAD, STAD, and ESCA with The Cancer Genome Atlas (TCGA) data. Our results for the first time showed that LLPS regulatory factors, such as Brd4, FBN1, and TP53, were frequently mutated in all types of digestive system tumors. Variant allele frequency (VAF) and APOBEC analysis demonstrated that genetic alterations of LLPS regulators were related to the progression of digestive system neoplasms (DSNs), such as TP53, NPHS1, TNRC6B, ITSN1, TNPO1, PML, AR, BRD4, DLG4, and PTPN1. KM plotter analysis showed that the mutation status of LLPS regulators was significantly related to the overall survival (OS) time of DSNs, indicating that they may contribute to the progression of DSN. The expression analysis of LLPS regulatory factors showed that a variety of LLPS regulatory factors were significantly dysregulated in digestive system tumors, such as SYN2 and MAPT. It is worth noting that we first found that LLPS regulatory factors were significantly correlated with tumor immune infiltration of B cells, CD4+ T cells, and CD8+ T cells in digestive system tumors. Bioinformatics analysis showed that the LLPS regulators’ expression was closely related to multiple signaling, including the ErbB signaling pathway and T-cell receptor signaling pathway. Finally, several LLPS signatures were constructed and had a strong prognostic stratification ability in different digestive gland tumors. Finally, the results demonstrated the LLPS regulators’ signature score was significantly positively related to the infiltration levels of CD4+ T cells, neutrophil cells, macrophage cells, and CD8+ T cells.Conclusion: Our study for the first time showed the potential roles of LLPS regulators in carcinogenesis and provide novel insights to identify novel biomarkers for the prediction of immune therapy and prognosis of DSNs.

ObjectiveTo evaluate the association between single-nucleotide polymorphisms (SNPs) in RNA-seq identified mRNAs and silicosis susceptibility.MethodsA comprehensive RNA-seq was performed to screen for differently expressed mRNAs in the peripheral blood lymphocytes of eight subjects exposed to silica dust (four silicosis cases and four healthy controls). Following this, the SNPs located on the shortlisted mRNAs, which may affect silicosis susceptibility, were screened through silicosis-related genome-wide association studies (GWAS) (155 silicosis cases and 141 healthy controls), whereas functional expression quantitative trait locus (eQTL)-SNPs were identified using the GTEx database. Finally, the association between functional eQTL-SNPs and silicosis susceptibility (194 silicosis cases and 235 healthy controls) was validated.ResultsA total of 70 differentially expressed mRNAs (fold change > 2 or fold change < 0.5, P < 0.05) was obtained using RNA-seq. Furthermore, 476 SNPs located on the shortlisted mRNAs, which may affect silicosis susceptibility (P < 0.05) were obtained using GWAS, whereas subsequent six functional eQTL-SNPs were identified. The mutant A allele of rs9273410 in HLA-DQB1 indicated a potential increase in silicosis susceptibility in the validation stage (additive model: odds ratio (OR)= 1.31, 95% confidence interval (CI) = 0.99–1.74, P = 0.061), whereas the combination of GWAS and the validation results indicated that the mutant A allele of rs9273410 was associated with increased silicosis susceptibility (additive model: OR = 1.35, 95% CI =1.09–1.68, P = 0.006).ConclusionThe mutant A allele of rs9273410 was associated with increased silicosis susceptibility by modulating the expression of HLA-DQB1.

Combining cryo-electron tomography with subtomogram averaging (StA) allows the in situ structure determination of proteins and protein complexes. Here, the authors present the hybrid StA (hStA) workflow that combines the advantages of single particle cryo-EM and StA and consists of a tomographic data collection scheme and a data processing workflow and they demonstrate how hStA can improve the resolution using two examples: the ion channel RyR1 and tobacco mosaic virus.

Abstract Aim The purpose of this study was to compare clinicopathological features of patients with non-schistosomal and schistosomal colorectal cancer to explore the effect of schistosomiasis on colorectal cancer (CRC) patients’ clinical outcomes. Methods Three hundred fifty-one cases of CRC were retrospectively analyzed in this study. Survival curves were constructed by using the Kaplan-Meier (K-M) method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables. Results Colorectal cancer patients with schistosomiasis (CRC-S) were significantly older (P < 0.001) than the patients without schistosomiasis (CRC-NS). However, there were no significant differences between CRC-S and CRC-NS patients in other clinicopathological features. Schistosomiasis was associated with adverse overall survival (OS) upon K-M analysis (P = 0.0277). By univariate and multivariate analysis, gender (P = 0.003), TNM stage (P < 0.001), schistosomiasis (P = 0.025), lymphovascular invasion (P = 0.030), and lymph nodes positive for CRC (P < 0.001) were all independent predictors in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was also an independent predictor in patients with stage III–IV tumors and in patients with lymph node metastasis, but not in patients with stage I–II tumors and in patients without lymph node metastasis. Conclusion Schistosomiasis was significantly correlated with OS, and it was an independent prognostic factor for OS in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was still an independently unfavorable prognosis factor for OS in patients with stage III–IV tumors or patients with lymph node metastasis.

Abstract Background The optimal revascularization technique in diabetic patients with complex coronary artery disease (CAD), including left main CAD and multivessel coronary disease (MVD), remains controversial. The current study aimed to compare adverse clinical endpoints of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM). Methods Relevant studies were found from MEDLINE, OVID, Science Direct, Embase and the Cochrane Central database from January 2010 to April 2019. Risk ratio (RR) with 95% confidence interval (CI) was used to express the pooled effect on discontinuous variables. Outcomes evaluated were all-cause mortality, major adverse cardiac/cerebrovascular events (MACCE), cardiac death, myocardial infarction, stroke, and repeat revascularization. Results Sixteen studies were included (18,224 patients). PCI was associated with the increase risk for MACCE (RR 1.59, 95% CI 1.38–1.85), cardiac death (RR 1.76, 95% CI 1.11–2.80), MI (RR 1.98, 95% CI 1.53–2.57), repeat revascularization (RR 2.61, 95% CI 2.08–3.29). The risks for all-cause mortality (RR 1.23, 95% CI 1.00–1.52) and stroke (RR 0.71, 95% CI 0.48–1.03) were similar between two strategies. Stratified analysis based on studies design and duration of follow-up showed largely similar findings with the overall analyses, except for a significant increased risk of all-cause mortality (RR 1.32, 95% CI 1.04–1.67) in long-term group, and CABG was associated with a higher stroke rate compared to PCI, which are results that were found in RCTs (RR 0.47, 95% CI 0.28–0.79) and mid-term groups (RR 0.39, 95% CI 0.23–0.66). Conclusions CABG was superior to PCI for diabetic patients with complex CAD (including left main CAD and/or MVD), but might be associated with a higher risk of stroke mid-term follow-up. Number of Protocol registration PROSPERO CRD 42019138505.

Abstract Early embryonic arrest and fragmentation (EEAF) is a common phenomenon leading to female infertility, but the genetic determinants remain largely unknown. The Moloney sarcoma oncogene (MOS) encodes a serine/threonine kinase that activates the ERK signaling cascade during oocyte maturation in vertebrates. Here, we identified four rare variants of MOS in three infertile female individuals with EEAF that followed a recessive inheritance pattern. These MOS variants encoded proteins that resulted in decreased phosphorylated ERK1/2 level in cells and oocytes, and displayed attenuated rescuing effects on cortical F‐actin assembly. Using oocyte‐specific Erk1/2 knockout mice, we verified that MOS‐ERK signal pathway inactivation in oocytes caused EEAF as human. The RNA sequencing data revealed that maternal mRNA clearance was disrupted in human mature oocytes either with MOS homozygous variant or with U0126 treatment, especially genes relative to mitochondrial function. Mitochondrial dysfunction was observed in oocytes with ERK1/2 deficiency or inactivation. In conclusion, this study not only uncovers biallelic MOS variants causes EEAF but also demonstrates that MOS‐ERK signaling pathway drives human oocyte cytoplasmic maturation to prevent EEAF.

Data-based technologies have been implemented in urban planning projects and environmental sciences. However, in the field of the environmental attractiveness analysis of seaside urban space, these technologies have not been fully studied. This paper critically assesses the attractiveness using data-based technologies with a focus on Chinese seaside cities’ low-carbon development. The analysis addresses the research question: How to use data-based technologies and their instruments to analyze environmental attractiveness of seaside cities towards low-carbon development? Methodologies include a case study of Dalian (China), field investigation, observation, and heatmapping. Results indicate that data-based technologies can support analysis of behavior and activity interests of inhabitants, as well as heatmapping with attractiveness consideration. The results provide a rational foundation for decision making during urban planning of seaside cities. Findings include insights and principles of planning seaside urban areas for smart sustainable development.

Starch is one of the main utilization products of sorghum (Sorghum bicolor L.), the fifth largest cereal crop in the world. Up to now, the regulation mechanism of starch biosynthesis is rarely documented in sorghum. In the present study, we identified 30 genes encoding the C2-C2 zinc finger domain (DOF), with one to three exons in the sorghum genome. The DOF proteins of sorghum were divided into two types according to the results of sequence alignment and evolutionary analysis. Based on gene expressions and co-expression analysis, we identified a regulatory factor, SbDof21, that was located on chromosome 5. SbDof21 contained two exons, encoding a 36.122 kD protein composed of 340 amino acids. SbDof21 co-expressed with 15 genes involved in the sorghum starch biosynthesis pathway, and the Pearson correlation coefficients (PCCs) with 11 genes were greater than 0.9. The results of qRT-PCR assays indicated that SbDof21 is highly expressed in sorghum grains, exhibiting low relative expression levels in the tissues of roots, stems and leaves. SbDOF21 presented as a typical DOF transcription factor (TF) that was localized to the nucleus and possessed transcriptional activation activity. Amino acids at positions 182–231 of SbDOF21 formed an important structure in its activation domain. The results of EMSA showed that SbDOF21 could bind to four tandem repeats of P-Box (TGTAAAG) motifs in vitro, such as its homologous proteins of ZmDOF36, OsPBF and TaPBF. Meanwhile, we also discovered that SbDOF21 could bind and transactivate SbGBSSI, a key gene in sorghum amylose biosynthesis. Collectively, the results of the present study suggest that SbDOF21 acts as an important regulator in sorghum starch biosynthesis, exhibiting potential values for the improvement of starch contents in sorghum.

A De Garengeot hernia is a rare type of femoral hernia that involves a vermiform appendix within a femoral hernia sac. Because of the rarity of this disease, a standard surgical procedure has not been established, and most cases are diagnosed intraoperatively. Preoperative diagnosis of a De Garengeot hernia is quite difficult. Computed tomography is the most sensitive and specific technique among the available imaging tests for preoperative diagnosis of a De Garengeot hernia. Although a standard surgical procedure is lacking, prompt surgery has become the consensus. The most common procedure is the open anterior approach; this allows exploration of the hernia sac and rapid treatment of its contents, routine appendectomy through a single incision, and preperitoneal repair of the femoral hernia.

Background and Aims: Studies have highlighted the role of the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio on subsequent cardiovascular events. However, the association of the TG/HDL-C ratio with survival outcomes in diabetic patients with coronary artery disease (CAD) treated with statins remains unknown. This study aimed to assess the predictive value of the TG/HDL-C ratio for all-cause mortality and cardiovascular death in diabetic patients with CAD treated with statins.Methods: The data of patients with type 2 diabetes and angiographically-confirmed CAD who were undergoing statin therapy and visited Tianjin Chest Hospital between January 2016 and September 2016 were retrospectively collected. The patients were categorized based on the baseline TG/HDL-C ratio tertile. Kaplan-Meier analysis and multivariate Cox proportional hazard regression were applied to assess the role of the TG/HDL-C ratio in predicting all-cause mortality and cardiovascular death.Results: A total of 2,080 patients were included. During the 4-year follow-up, 209 patients died, 136 of whom from cardiovascular death. The Kaplan-Meier analyses showed that an increased TG/HDL-C ratio was associated with an increased risk of all-cause mortality (P < 0.001) and cardiovascular death (P < 0.001). The multivariate cox hazard regression analysis revealed a similar effect of the TG/HDL-C ratio on the risk of all-cause mortality (P = 0.046) and cardiovascular death (P = 0.009). The role of the TG/HDL-C ratio in predicting all-cause mortality and cardiovascular death was similar among all subgroups (P > 0.050). For all-cause mortality, the TG/HDL-C ratio significantly improved the C-statistic from 0.799 to 0.812 (P = 0.018), and the net reclassification index (NRI) and integrated discrimination index (IDI) were 0.252 (95% CI: 0.112–0.392; P < 0.001) and 0.012 (95% CI: 0.003–0.022; P = 0.012), respectively. Similarly, for cardiovascular death, the TG/HDL-C ratio significantly improved the C-statistic from 0.771 to 0.804 (P < 0.001), and the NRI and IDI were 0.508 (95% CI: 0.335–0.680; P < 0.001) and 0.033 (95% CI: 0.015–0.050; P < 0.001).Conclusion: TG/HDL-C ratio might be useful for predicting all-cause mortality and cardiovascular death in diabetic patients with CAD treated with statins.

Zinc ash is a by-product of the hot-dip galvanizing process and the electrolytic zinc process, which is classified as a hazardous waste consisting predominately of zinc oxide that could be recovered as the useful main resource for ZnO preparation. In this work, in order to reduce the energy consumption of the direct reduction process and improve the resource-recovery rate. A new technology for zinc oxide production, by a carbothermal reduction of zinc ash, is proposed. This process includes two steps: high-temperature roasting of zinc ash for dechlorination and a carbothermal reduction of dechlorination ash. Zn in zinc ash is mainly presented in the form of zinc oxide (ZnO), basic zinc chloride (Zn5(OH)8Cl2H2O), and metallic zinc (Zn). Basic zinc chloride can be roasted and decomposed to reduce the chlorine content in zinc ash. The results of a chloride ion removal test show that the optimal roasting temperature is 1000 °C, with a holding time of 60 min. Under the modified conditions, the chloride content in the roasted zinc ash is reduced to 0.021 wt.%, and the dechlorination rate is more than 99.5%, which can meet the requirements of zinc oxide production. The best process conditions for zinc oxide production by carbothermic reduction are as follows: reduction temperature of 1250 °C, reduction time of 60 min, and reduction agent addition of 22 wt.%. Under the best reduction process, the purity of zinc oxide product is 99.5%, and the recovery of zinc is more than 99.25%. Needle-like zinc oxide obtained by carbothermic reduction has high purity and can replace zinc oxide produced by an indirect process.

Cyclophosphamide (CTX) is widely used in various cancer therapies and in immunosuppression, and patients can still have babies after CTX chemotherapy. CTX directly causes primordial follicle loss with overactivation and DNA damage-induced apoptosis. Previous studies have shown that maternal exposure to CTX before conception increases the incidence of birth abnormalities and alters the methylation of genes in the oocytes of offspring. Mice were treated with a single dose of CTX (100 mg/kg) at post-natal day 21 and sacrificed 47 days later when primordial follicles surviving chemotherapy developed to the antral stage. Acute DNA damage and acceleration of the activation of primordial follicles after CTX treatment were repaired within several days, but the remaining follicle numbers remarkably decrease. Although partial surviving primordial follicle were developed to mature oocyte, oocyte quality hemostasis was impaired exhibiting aberrant meiosis progression, abnormal spindle and aneuploidy, mitochondrial dysfunction and increased endoplasmic reticulum stress. Thereafter, embryo development competency significantly decreased with fewer blastocyst formation after CTX exposure. CTX treatment resulted in alteration of DNA methylations and histone modifications in fully grown GV oocytes. Single-cell RNA-seq revealed CTX treatment suppressed multiple maternal genes’ transcription including many methyltransferases and maternal factor YAP1, which probably accounts for low quality of CTX-repaired oocyte. In vitro addition of lysophosphatidic acid (LPA) to embryo culture media to promote YAP1 nuclear localization improved CTX-repaired embryo developmental competence. This study provides evidence for the consistent toxic effect of CTX exposure during follicle development, and provide a new mechanism and new insights into future clinical interventions for fertility preservation.

Coordination of neurite extension with surrounding glia development is critical for neuronal function, but the underlying molecular mechanisms remain poorly understood. Through a genome-wide mutagenesis screen in C. elegans, we identified dyf-4 and daf-6 as two mutants sharing similar defects in dendrite extension. DAF-6 encodes a glia-specific patched-related membrane protein that plays vital roles in glial morphogenesis. We cloned dyf-4 and found that DYF-4 encodes a glia-secreted protein. Further investigations revealed that DYF-4 interacts with DAF-6 and functions in a same pathway as DAF-6 to regulate sensory compartment formation. Furthermore, we demonstrated that reported glial suppressors of daf-6 could also restore dendrite elongation and ciliogenesis in both dyf-4 and daf-6 mutants. Collectively, our data reveal that DYF-4 is a regulator for DAF-6 which promotes the proper formation of the glial channel and indirectly affects neurite extension and ciliogenesis.

Objective To investigate the relationship between lipoprotein(a) gene ( LPA ) polymorphisms and calcific aortic valve disease (CAVD) and coronary heart disease (CHD) in Han Chinese. Methods A total of 148 patients were recruited (n = 71 with CAVD and n = 77 with CHD) based on a diagnosis achieved using color Doppler echocardiography, coronary angiography, or computed tomography angiography. Seventy-one control individuals without CAVD or CHD were also recruited. Biomarkers including levels of lipoprotein(a) [Lp(a)], low-density lipoprotein and high-density lipoprotein cholesterol, apolipoprotein A1, and apolipoprotein B were tested. LPA polymorphisms rs10455872, rs6415084, rs3798221, and rs7770628 were analyzed using SNaPshot SNP. Results Lp(a) levels were significantly higher in CAVD and CHD groups compared with controls. There was no significant difference in the allelic frequency distribution of rs3798221, rs7770628, or rs6415084 between CHD, CAVD, and control groups. Linear regression showed that rs3798221, rs7770628, and rs6415084 were associated with increased Lp(a) concentrations. Two CAVD patients among the 219 participants carried AG minor alleles at rs10455872, while the remainder carried AA minor alleles. Conclusion rs3798221, rs6415084, and rs7770628 polymorphisms within LPA are associated with higher Lp(a) plasma levels, which correlate with increased CAVD and CHD risks.

Background: Recent studies have shown that blood-based miRNAs are dysregulated in patients with acute myocardial infarction (AMI) and are therefore a potential tool for the diagnosis of AMI. Therefore, this study summarized and evaluated studies focused on microRNAs as novel biomarkers for the diagnosis of AMI from the last ten years.Methods: MEDLINE, the Cochrane Central database, and EMBASE were searched between January 2010 and December 2019. Studies that assessed the diagnostic accuracy of circulating microRNAs in AMI were chosen. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve (AUC) were used to assess the test performance of miRNAs.Results: A total of 58 studies that included 8,206 participants assessed the diagnostic accuracy of circulating miRNAs in AMI. The main results of the meta-analyses are as follows: (1) Total miRNAs: the overall pooled sensitivity and specificity were 0.82 (95% CI: 0.79–0.85) and 0.87 (95% CI: 0.84–0.90), respectively. The AUC value was 0.91 (95% CI: 0.88–0.93) in the overall summary receiver operator characteristic (SROC) curve. (2) The panel of two miRNAs: sensitivity: 0.88 (95% CI: 0.77–0.94), specificity: 0.84 (95% CI: 0.72–0.91), AUC: 0.92 (95% CI: 0.90–0.94). (3) The panel of three miRNAs: sensitivity: 0.91 (95% CI: 0.85–0.94), specificity: 0.87 (95% CI: 0.77–0.92), AUC: 0.92 (95% CI: 0.89–0.94). (4) Results by types of miRNAs: miRNA-1: sensitivity: 0.78 (95% CI: 0.71–0.84), specificity: 0.86 (95% CI: 0.77–0.91), AUC: 0.88 (95% CI: 0.85–0.90); miRNA-133a: sensitivity: 0.85 (95% CI: 0.69–0.94), specificity: 0.92 (95% CI: 0.61–0.99), AUC: 0.93 (95% CI: 0.91–0.95); miRNA-208b: sensitivity: 0.80 (95% CI: 0.69–0.88), specificity: 0.96 (95% CI: 0.77–0.99), AUC: 0.91 (95% CI: 0.88–0.93); miRNA-499: sensitivity: 0.85 (95% CI: 0.77–0.91), specificity: 0.95 (95% CI: 0.89–0.98), AUC: 0.96 (95% CI: 0.94–0.97).Conclusion: miRNAs may be used as potential biomarkers for the detection of AMI. For single, stand-alone miRNAs, miRNA-499 may have better diagnostic accuracy compared to other miRNAs. We propose that a panel of multiple miRNAs with high sensitivity and specificity should be tested.

Objective Statins have been shown to be beneficial for the prevention of cardiovascular events. In elderly individuals, the efficacy of statins remains controversial and the comparative effect of statins has not been assessed. Methods MEDLINE, Embase, and the Cochrane Central database were searched for randomized controlled trials that assessed statins in older patients. Results Seventeen trials were analyzed. When used for secondary prevention, statins were associated with reduced risk of cardiovascular events, all-cause mortality, cardiovascular mortality, revascularization, and stroke. When used for primary prevention, statins reduced the risk of myocardial infarction and revascularization, but did not significantly affect other outcomes. A modest difference between pharmaceutical statin products was found, and high-quality evidence indicated that intensive atorvastatin had the greatest benefits for secondary prevention. Conclusions In secondary prevention, evidence strongly suggests that statins are associated with a reduction in the risk of all-cause mortality, cardiovascular events, cardiovascular mortality, and revascularization. However, differences in the effects of various statins do not appear to have significant effects on therapy in secondary prevention for the elderly.

Gastric cancer (GC) is one of the most common types of human cancers. However, the mechanisms underlying GC remained largely unclear. To determine whether the differentially expressed mRNAs, lncRNAs and circRNAs in GC, we screened conducted SBC-ceRNA microarray analysis in 3 pairs of GC and normal tissues. Furthermore, differentially expressed mRNAs mediated protein protein interaction (PPI) networks, lncRNAs mediated cis-regulatory network, and circRNA mediated ceRNA network were for the first time constructed to reveal their potential functions and mechanisms in GC. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) was conducted to validate the microarray analysis. A total of 922 mRNAs, 2112 lncRNAs and 2896 circRNAs were observed to be dysregulated in GC samples. Bioinformatics analysis showed these differentially expressed genes (DEGs) were significantly associated with regulating branched − chain amino acid catabolic process, Glycolysis/Gluconeogenesis and ARF protein signal transduction. Moreover, we found the dysregulation of key mRNAs and lncRNAs were associated with the overall survival time in GC patients. We believe this study provides useful information for understanding the mechanism underlying GC progression and exploring potential therapeutic and prognostic targets for GC.

Buildings’ outdoor thermal comfort influences environment quality and human behavior in urban neighborhoods. The Universal Thermal Climate Index (UTCI) has been broadly applied to the study of buildings’ outdoor thermal comfort in urban areas. However, complex environmental conditions in climate-sensitive urban areas can make UTCI assessment complicated and ineffective. This paper introduces digital techniques into buildings’ outdoor thermal comfort analysis for the improvement of the urban habitant environment. A digital simulation system is generated to facilitate the analysis procedure for buildings’ outdoor thermal comfort assessment in urban neighborhoods. The analysis addresses the research question: “Can digital simulation techniques provide a modeling system to assess buildings’ outdoor thermal comfort continuously and effectively?” Methods include a case study of neighborhoods in Beijing, qualitative and quantitative analysis based on digital processes, and parametric modeling. The results indicate that digital simulation techniques and tools have the capability to support the analysis of buildings’ outdoor thermal comfort by providing three-dimensional models, algorithm-based analysis, and visual simulation. The findings include a critique of digital simulation as applied to architecture study and insights on potentially improving buildings’ outdoor thermal comfort through human–computer interactions.

CRISPR-Cas9 is widely used for genome engineering but structural data for the DNA cleavage step are still incomplete. Here, the authors present the cryo-EM structure of a ternary Cas9-sgRNA-target DNA complex, perform MD simulations and discuss implications for the Cas9 DNA cleavage mechanism.