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Abstract In recent research on building materials, researchers have increasingly focused on replacing cement with agricultural waste. This approach offers significant advantages in terms of reducing global CO2 emissions and promoting the sustainability of building materials. In this paper, the use of the agricultural waste walnut shell ash (WSA) to partially replace cement in sustainable green mortars is explored. Specifically, equal amounts of WSA (5%, 10% and 15%) were used to replace cement. To offset the reduction in strength caused by the partial replacement of cement with WSA, basalt fibers were added to the mortar mixture. The effect of these fibers on the mechanical properties of the WSA-reinforced mortar was examined in compression tests, split tensile tests, and flexural fatigue cycle tests. In the flexural fatigue tests, the parameter and length of basalt fibers were varied and different stress levels (0.85, 0.8 and 0.75) were applied. The fatigue equations were developed using the Weibull model and p–s–n curves with a survival probability of 0.5 were derived. The results showed that the compressive strength and split tensile strength of the specimens increased with the addition of basalt fibers, with maximum values of 34.7 MPa and 3.8 MPa, respectively, and maximum increases of 8.78% and 21.95%, respectively. In addition, the average fatigue life of WSA mortar was 247,541 cycles, which increased by 139.26% when the stress level was 0.75, fiber length was 9 mm, and dosage was 0.3%. The linear regression fitting showed good correlation and provided valuable insights for practical engineering applications.

Abstract Development of potent and broad-spectrum antimicrobial peptides (AMPs) could help overcome the antimicrobial resistance crisis. We develop a peptide language-based deep generative framework (deepAMP) for identifying potent, broad-spectrum AMPs. Using deepAMP to reduce antimicrobial resistance and enhance the membrane-disrupting abilities of AMPs, we identify, synthesize, and experimentally test 18 T1-AMP (Tier 1) and 11 T2-AMP (Tier 2) candidates in a two-round design and by employing cross-optimization-validation. More than 90% of the designed AMPs show a better inhibition than penetratin in both Gram-positive (i.e., S. aureus) and Gram-negative bacteria (i.e., K. pneumoniae and P. aeruginosa). T2-9 shows the strongest antibacterial activity, comparable to FDA-approved antibiotics. We show that three AMPs (T1-2, T1-5 and T2-10) significantly reduce resistance to S. aureus compared to ciprofloxacin and are effective against skin wound infection in a female wound mouse model infected with P. aeruginosa. In summary, deepAMP expedites discovery of effective, broad-spectrum AMPs against drug-resistant bacteria.

Abstract Background Obesity and its associated complications raise significant public concern, revealing gender disparities in the susceptibility to metabolic disorders, with females often displaying greater resistance to obesity-related metabolic disorder than males. Sestrin2 is a crucial protein involved in metabolism and energy balance. This study seeks to explore whether Sesn2 knockout (KO) exacerbates high-fat diet (HFD) induced obesity in female mice. Methods Female mice with wild-type (WT) and Sesn2 KO were subjected to a 12-week regimen of normal diet or HFD. Using a Body Composition Analyzer, body composition was gauged. Biochemical assays encompassed glucose, lipid, and liver function measurements, alongside 24-hour urine albumin excretion. Echocardiographic evaluation assessed cardiac function. Histopathological analysis of key metabolic tissues (liver, kidney, and heart tissues) were conducted. Western blotting or qRT-PCR evaluated key proteins and genes linked to inflammation, mitochondrial, and lipid metabolism in adipose tissues. Results In comparison to mice fed a regular diet, those on a HFD exhibited significant increases in body weight and fat mass. Notably, Sesn2 KO further aggravated obesity, showcasing the most pronounced metabolic anomalies: elevated body weight, fat mass, impaired glucose tolerance, and insulin sensitivity, alongside heightened levels of free fatty acids and triglycerides. Additionally, KO-HFD mice displayed exacerbated multi-tissue impairments, including elevated hepatic enzymes, increased urinary albumin excretion, compromised cardiac function, and accumulation of lipids in the liver, kidney, and heart. Moreover, adipose tissue showcased altered lipid dynamics and function, characterized by enhanced triglyceride breakdown and modified adipokine levels. Browning was diminished, along with decreased Pgc1α and Sirt1 in KO-HFD mice. Conclusion Sesn2 KO exacerbates HFD-induced obesity and metabolic disorders in female mice. These findings underscore Sestrin2’s novel role as a regulator of obesity in female mice.

Abstract Background Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity. Methods Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents. Results Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity. Conclusions The study suggest that the ketogenic diet had an unfavorable risk–benefit trade-off and may compromise metabolic homeostasis in obese mice.

Summary: Advanced glycation end products (AGEs) in diabetes can cause endothelial damage. Heparin, widely known as a recognized anticoagulant, is also a multifunctional therapeutic drug. This study investigated whether heparin could ameliorate AGEs-induced endothelial injury. Remarkably, heparin effectively attenuated this cellular damage and assumed a reparative role. Furthermore, heparin inhibited the AGEs-RAGE-NFκB axis, thereby mitigating endothelial inflammatory injury. Comprehensive proteome and knockdown experiments suggested that heparin may exert a positive influence on cell growth and further alleviate pathological damage by upregulating the expression of LYAR (cell growth-regulating nucleolar protein). Diabetic mouse model was also used to further verify the changes of endothelial tissue in diabetic state and heparin intervention. In summary, these findings demonstrate that heparin has the potential to ameliorate AGEs-induced endothelial injury, opening new avenues for exploring the expanded therapeutic roles of heparin and its potential application in the management of diabetes and its associated complications.

Microbial interactions are widespread and important processes that support the link between disease and microbial ecology. The gut microbiota is a major source of microbial stimuli that can have detrimental or beneficial effects on human health. It is also an endocrine organ that maintains energy homeostasis and host immunity. Obesity is a highly and increasingly prevalent metabolic disease and the leading cause of preventable death worldwide. An imbalance in the gut microbiome is associated with several diseases including obesity-related metabolic disorders. This review summarizes the complex association between the gut microbiome and obesity-associated metabolic diseases and validates the role and mechanisms of ecological dysregulation in the gut in obesity-associated metabolic disorders. Therapies that could potentially alleviate obesity-associated metabolic diseases by modulating the gut microbiota are discussed.

Abstract Background Circulating tumor cell (CTC) clusters play a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have retarded the research progress. In vitro CTC clusters model can help to further understand the biological properties of CTC clusters and their clinical significance. Therefore, it is necessary to establish reliable in vitro methodological models to form CTC clusters whose biological characteristics are very similar to clinical CTC clusters. Methods The assays of immunofluorescence, transmission electron microscopy, EdU incorporation, cell adhension and microfluidic chips were used. The experimental metastasis model in mice was used. Results We systematically optimized the culture methods to form in vitro CTC clusters model, and more importantly, evaluated it with reference to the biological capabilities of reported clinical CTC clusters. In vitro CTC clusters exhibited a high degree of similarity to the reported pathological characteristics of CTC clusters isolated from patients at different stages of tumor metastasis, including the appearance morphology, size, adhesive and tight junctions-associated proteins, and other indicators of CTC clusters. Furthermore, in vivo experiments also demonstrated that the CTC clusters had an enhanced ability to grow and metastasize compared to single CTC. Conclusions The study provides a reliable model to help to obtain comparatively stable and qualified CTC clusters in vitro, propelling the studies on tumor metastasis.

Abstract Self‐assembling peptides have numerous applications in medicine, food chemistry, and nanotechnology. However, their discovery has traditionally been serendipitous rather than driven by rational design. Here, HydrogelFinder, a foundation model is developed for the rational design of self‐assembling peptides from scratch. This model explores the self‐assembly properties by molecular structure, leveraging 1,377 self‐assembling non‐peptidal small molecules to navigate chemical space and improve structural diversity. Utilizing HydrogelFinder, 111 peptide candidates are generated and synthesized 17 peptides, subsequently experimentally validating the self‐assembly and biophysical characteristics of nine peptides ranging from 1–10 amino acids—all achieved within a 19‐day workflow. Notably, the two de novo‐designed self‐assembling peptides demonstrated low cytotoxicity and biocompatibility, as confirmed by live/dead assays. This work highlights the capacity of HydrogelFinder to diversify the design of self‐assembling peptides through non‐peptidal small molecules, offering a powerful toolkit and paradigm for future peptide discovery endeavors.

Glioblastoma (GBM) is a malignant brain tumor that grows quickly, spreads widely, and is resistant to treatment. Fibroblast growth factor receptor (FGFR)1 is a receptor tyrosine kinase that regulates cellular processes, including proliferation, survival, migration, and differentiation. FGFR1 was predominantly expressed in GBM tissues, and FGFR1 expression was negatively correlated with overall survival. We rationally designed a novel small molecule CYY292, which exhibited a strong affinity for the FGFR1 protein in GBM cell lines in vitro. CYY292 also exerted an effect on the conserved Ser777 residue of FGFR1. CYY292 dose-dependently inhibited cell proliferation, epithelial–mesenchymal transition, stemness, invasion, and migration in vitro by specifically targeting the FGFR1/AKT/Snail pathways in GBM cells, and this effect was prevented by pharmacological inhibitors and critical gene knockdown. In vivo experiments revealed that CYY292 inhibited U87MG tumor growth more effectively than AZD4547. CYY292 also efficiently reduced GBM cell proliferation and increased survival in orthotopic GBM models. This study further elucidates the function of FGFR1 in the GBM and reveals the effect of CYY292, which targets FGFR1, on downstream signaling pathways directly reducing GBM cell growth, invasion, and metastasis and thus impairing the recruitment, activation, and function of immune cells.

Summary: The global burden of diseases and injuries poses complex and pressing challenges. This study analyzed 369 diseases and injuries attributed to 84 risk factors globally from 1990 to 2019, projecting trends to 2040. In 2019, global risks caused 35 million deaths. Non-communicable diseases were responsible for 8.2 million deaths, primarily from air pollution (5.5 million). Cardiovascular disease from air pollution had a high age-standardized disability-adjusted life year rate (1,073.40). Communicable, maternal, neonatal, and nutritional diseases caused 1.4 million deaths, mainly due to unsafe water and sanitation. Occupational risks resulted in 184,269 transport-related deaths. Behavioral risks caused 21.6 million deaths, with dietary factors causing 6.9 million cardiovascular deaths. Diabetes linked to sugar-sweetened beverages showed significant growth (1990–2019). Metabolic risks led to 18.6 million deaths. Projections to 2040 indicated persistent challenges, emphasizing the urgent need for targeted interventions and policies to alleviate the global burden of diseases and injuries.

Abstract Background Colorectal cancer (CRC) is one of the most common tumors in the world. Cholesterol plays an important role in the pathogenesis of tumors. One of the cholesterol transporters, scavenger receptor class B type 1 (SR‐B1), a multi‐ligand membrane receptor protein, is expressed in the intestines which also highly expressed in various tumors. But the potential mechanism of SR‐B1 in CRC development has not been reported. Aims This study aimed to clarify the importance of SR‐B1 in the development and prognosis of CRC as much as possible to provide a possible strategy in CRC treatment. Materials & Methods In this study, we used SR‐B1 gene knockdown mice to study the effect of SR‐B1 on colitis‐induced or APCmin/+‐induced CRC. The expression of related molecules were detected through the immunohistochemistry and hematoxylin–eosin staining, western blot analysis, and Flow cytometry. The gene expression and microbiota in microenvironment of CRC mice were analyzed through eukaryotic mRNA sequencing and 16S rRNA high‐throughput sequencing. Results The results showed that SR‐B1 knockdown reduced the tumor load of colitis‐induced or APCmin/+‐induced CRC. SR‐B1 knockdown improved the immune microenvironment by affecting the level of tumor‐associated macrophage (TAM), mononuclear myeloid‐derived suppressor cells (M‐MDSCs), granulocytic myeloid‐derived suppressor cells (G‐MDSCs), programmed cell death‐ligand 1 (PD‐L1), and human leukocyte antigen class I‐B (HLA‐B), and also reduced the level of low‐density lipoprotein receptor (LDL‐R), and increased the level of ATP binding cassette transporter A1 (ABCA1) to regulate the cholesterol metabolism, and regulated the expression of related genes and intestinal microbiota. SR‐B1 knockdown can also trigger the anti‐CRC effect of anti‐PD 1 in colitis‐induced CRC. Discussion SR‐B1 deficiency significantly improved the immunity in tumor microenvironment of colitis‐induced or APCmin/+‐induced CRC. In addition, the microbiota changes caused by SR‐B1 deficiency favor improving the immune response to chemotherapeutic drugs and anti‐PD1 therapy. The mechanism of action of SR‐B1 deficiency on the development of CRC still needs further in‐depth research. Conclusion This study provides a new treatment strategy for treating CRC by affecting the expression of SR‐B1 in intestine.

The shale oil and gas exploitation in China is technically benchmarked with the United States in terms of development philosophy, reservoir stimulation treatment, fracturing parameters, fracturing equipment and materials, oil/gas production technology, and data/achievements sharing. It is recognized that the shale oil and gas exploitation in China is weak in seven aspects: understanding of flow regimes, producing of oil/gas reserves, monitoring of complex fractures, repeated stimulation technology, oil/gas production technology, casing deformation prevention technology, and wellbore maintenance technology. Combined with the geological and engineering factors of shale oil and gas in China, the development suggestions of four projects are proposed from the macro- and micro-perspective, namely, basic innovation project, exploitation technology project, oil/gas production stabilization project, and supporting efficiency-improvement project, so as to promote the rapid, efficient, stable, green and extensive development of shale oil and gas industry chain and innovation chain and ultimately achieve the goal of “oil volume stabilizing and gas volume increasing”.

Abstract Background The first telomere-to-telomere (T2T) human genome assembly (T2T-CHM13) release is a milestone in human genomics. The T2T-CHM13 genome assembly extends our understanding of telomeres, centromeres, segmental duplication, and other complex regions. The current human genome reference (GRCh38) has been widely used in various human genomic studies. However, the large-scale genomic differences between these two important genome assemblies are not characterized in detail yet. Results Here, in addition to the previously reported “non-syntenic” regions, we find 67 additional large-scale discrepant regions and precisely categorize them into four structural types with a newly developed website tool called SynPlotter. The discrepant regions (~ 21.6 Mbp) excluding telomeric and centromeric regions are highly structurally polymorphic in humans, where the deletions or duplications are likely associated with various human diseases, such as immune and neurodevelopmental disorders. The analyses of a newly identified discrepant region—the KLRC gene cluster—show that the depletion of KLRC2 by a single-deletion event is associated with natural killer cell differentiation in ~ 20% of humans. Meanwhile, the rapid amino acid replacements observed within KLRC3 are probably a result of natural selection in primate evolution. Conclusion Our study provides a foundation for understanding the large-scale structural genomic differences between the two crucial human reference genomes, and is thereby important for future human genomics studies.

Bone morphogenetic protein (BMP-2) has been approved by the FDA to promote bone regeneration, but uncertain osteogenic effect and dose-dependent side effects may occur. Osteoimmunomodulation plays an important role in growth factor-based osteogenesis. Here, we explored how proinflammatory signals affect the dose-dependent osteogenic potential of BMP-2. We observed that the expression level of local IL-1β did not increase with the dose of BMP-2 in the mouse osteogenesis model. A low dose of BMP-2 could not promote new bone formation, but trigger the release of IL-1β from M1 macrophages. As the dose of BMP-2 increased, the IL-1β expression and M1 infiltration in local microenvironment were inhibited by IL-1Ra from MSCs under osteogenic differentiation induced by BMP-2, and new bone tissues formed, even excessively. Anti-inflammatory drugs (Dexamethasone, Dex) promoted osteogenesis via inhibiting M1 polarization and enhancing BMP-2-induced MSC osteo-differentiation. Thus, we suggest that the osteogenic effect of BMP-2 involves macrophage-MSC interaction that is dependent on BMP-2 dose and based on IL-1R1 ligands, including IL-1β and IL-1Ra. The dose of BMP-2 could be reduced by introducing immunoregulatory strategies.

Type II diabetes mellitus (TIIDM) remains a challenging clinical issue for both dentists and orthopedists. By virtue of persistent hyperglycemia and altered host metabolism, the pathologic diabetic micromilieu with chronic inflammation, advanced glycation end products accumulation, and attenuated biomineralization severely impairs bone regeneration efficiency. Aiming to “remodel” the pathologic diabetic micromilieu, we 3D-printed bioscaffolds composed of Sr-containing mesoporous bioactive glass nanoparticles (Sr-MBGNs) and gelatin methacrylate (GelMA). Sr-MBGNs act as a biomineralization precursor embedded in the GelMA-simulated extracellular matrix and release Sr, Ca, and Si ions enhancing osteogenic, angiogenic, and immunomodulatory properties. In addition to angiogenic and anti-inflammatory outcomes, this innovative design reveals that the nanocomposites can modulate extracellular matrix reconstruction and simulate biomineralization by activating lysyl oxidase to form healthy enzymatic crosslinked collagen, promoting cell focal adhesion, modulating osteoblast differentiation, and boosting the release of OCN, the noncollagenous proteins (intrafibrillar mineralization dependent), and thus orchestrating osteogenesis through the Kindlin-2/PTH1R/OCN axis. This 3D-printed bioscaffold provides a multifunctional biomineralization-inspired system that remodels the “barren” diabetic microenvironment and sheds light on the new bone regeneration approaches for TIIDM.

Proteinuria during pregnancy is closely related to the occurrence of adverse pregnancy outcomes. One hundred and forty-two women with proteinuria during pregnancy and followed between January 2018 and December 2020 were evaluated. Based on the 24-h proteinuria value, they were divided as mild (n = 76, 300–1000 mg/day), moderate (n = 39, 1000–3500 mg/day) and severe (n = 27, >3500 mg/day) proteinuria. The rates of prematurity, low birth weight and neonatal asphyxia were significantly higher in the severe proteinuria group than in the mild and moderate groups, while the rates of foetal growth restriction and neonatal intensive care unit admission were significantly higher in the severe compared with the mild proteinuria group (all p

Osteoclast differentiation is critical for bone homeostasis. The authors show the negative feedback regulation of BRD9-mediated chromatin remodeling on osteoclastogenesis via interferon beta signaling and its therapeutic potential for bone diseases.

Epithelial ovarian cancer (EOC) remains one of the leading causes of cancer-related deaths among women worldwide. Receptor tyrosine kinases (RTKs) have long been sought as therapeutic targets for EOC, as they are frequently hyperactivated in primary tumors and drive disease relapse, progression, and metastasis. More recently, these oncogenic drivers have been implicated in EOC response to poly(ADP-ribose) polymerase (PARP) inhibitors and epigenome-interfering agents. This evidence revives RTKs as promising targets for therapeutic intervention of EOC. This review summarizes recent studies on the role of RTKs in EOC malignancy and the use of their inhibitors for clinical treatment. Our focus is on the ERBB family, c-Met, and VEGFR, as they are linked to drug resistance and targetable using commercially available drugs. The importance of these RTKs and their inhibitors is highlighted by their impact on signal transduction and intratumoral heterogeneity in EOC and successful use as maintenance therapy in the clinic through suppression of the VEGF/VEGFR axis. Finally, the therapeutic potential of RTK inhibitors is discussed in the context of combinatorial targeting via co-inhibiting proliferative and anti-apoptotic pathways, epigenomic/transcriptional programs, and harnessing the efficacy of PARP inhibitors and programmed cell death 1/ligand 1 immune checkpoint therapies.

Subcellular organelles dysfunction is implicated in various diseases, including metabolic diseases, neurodegenerative diseases, cancer, and cardiovascular diseases. BAM15, a selective mitochondrial uncoupler, has emerged as a promising therapeutic agent due to its ability to enhance mitochondrial respiration and metabolic flexibility. By disrupting the coupling between electron transport and ATP synthesis, BAM15 dissipates the proton gradient, leading to increased mitochondrial respiration and energy expenditure. This review provides a comprehensive overview of BAM15, including its mechanism of action and potential therapeutic applications in diverse disease contexts. BAM15 has shown promise in obesity by increasing energy expenditure and reducing fat accumulation. In diabetes, it improves glycemic control and reverses insulin resistance. Additionally, BAM15 has potential in non-alcoholic fatty liver disease, sepsis, and cardiovascular diseases by mitigating oxidative stress, modulating inflammatory responses, and promoting cardioprotection. The safety profile of BAM15 is encouraging, with minimal adverse effects and remarkable tolerability. However, challenges such as its high lipophilicity and the need for alternative delivery methods need to be addressed. Further research is necessary to fully understand the therapeutic potential of BAM15 and optimize its application in clinical settings.

The clinical application of bone morphogenetic protein-2 (BMP-2) is limited by several factors, including ineffectiveness at low doses and severe adverse effects at high doses. To address these efficacy and safety limitations, we explored whether orchestration of energy metabolism and osteogenesis by magnesium ion (Mg2+) could reduce the dose and thereby improve the safety of BMP-2. Our results demonstrated that rapid metabolic activation triggered by BMP-2 was indispensable for subsequent osteogenesis. Moreover, inadequate metabolic stimulation was shown to be responsible for the ineffectiveness of low-dose BMP-2. Next, we identified that Mg2+, as an ''energy propellant'', substantially increased cellular bioenergetic levels to support the osteogenesis via the Akt-glycolysis-Mrs2-mitochondrial axis, and consequently enhanced the osteoinductivity of BMP-2. Based on the mechanistic discovery, microgel composite hydrogels were fabricated as low-dose BMP-2/Mg2+ codelivery system through microfluidic and 3D printing technologies. An in vivo study further confirmed that rapid and robust bone regeneration was induced by the codelivery system. Collectively, these results suggest that this bioenergetic-driven, cost-effective, low-dose BMP-2-based strategy has substantial potential for bone repair.

Abstract Purpose The aim of this study was to identify and screen long non-coding RNA (lncRNA) associated with immune genes in colon cancer, construct immune-related lncRNA pairs, establish a prognostic risk assessment model for colon adenocarcinoma (COAD), and explore prognostic factors and drug sensitivity. Method Our method was based on data from The Cancer Genome Atlas (TCGA). To begin, we obtained all pertinent demographic and clinical information on 385 patients with COAD. All lncRNAs significantly related to immune genes and with differential expression were identified to construct immune lncRNA pairs. Subsequently, least absolute shrinkage and selection operator and Cox models were used to screen out prognostic-related immune lncRNAs for the establishment of a prognostic risk scoring formula. Finally, We analysed the functional differences between subgroups and screened the drugs, and establish an individual prediction nomogram model. Results Our final analysis confirmed eight lncRNA pairs to construct prognostic risk assessment model. Results showed that the high-risk and low-risk groups had significant differences (training (n = 249): p

Background According to previous literatures, plasma thioredoxin reductase (TrxR) level was significantly elevated in various malignant tumors and serve as a potential biomarker for diagnosis and prognostic prediction. However, there is little awareness of the clinical value of plasma TrxR in gynecologic malignancies. In the present study, we aim to evaluate the diagnostic accuracy of plasma TrxR in gynecologic cancer and explore its role in treatment surveillance. Methods We retrospectively enrolled 134 patients with gynecologic cancer and 79 patients with benign gynecologic disease. The difference of plasma TrxR activity and tumor markers level between two groups was compared using Mann-Whitney U test. By detecting pretreatment and post-treatment level of TrxR and conventional tumor markers, we further assessed the change trend of them with the Wilcoxon signed-ranks test. Results Compared with benign control [5.7 (5, 6.6) U/mL], statistically significant increase of TrxR activity was observed in gynecologic cancer group [8.4 (7.25, 9.825) U/mL] ( P

Suspended waterproof curtains combined with pumping wells are the primary method for controlling groundwater levels in foundation pits within soft soil areas. However, there is still a lack of a systematic approach to predict the groundwater drawdown within the foundation pit caused by the influence of these suspended curtains. In order to investigate the variation of groundwater level within the excavation during dewatering processes, the finite difference method is employed to analyze the seepage characteristics of foundation pits with suspended waterproof curtains. Basing on the concept of equivalent well, this study examines the coupled effects of aquifer anisotropy (ki), aquifer thickness (Mi), well screen length (li), and the depth of waterproof curtain embedment on the seepage field distortion. A characteristic curve is established for standard conditions, which exposes the blocking effect of the curtain on the amount of groundwater drawdown in the pit. Additionally, correction coefficients are proposed for non-standard conditions, which, in turn, results in a prediction formula with a wider range of applicability. Comparative analysis between the calculated predictions and the field observation data from an actual foundation pit project in Zhuhai City validates the feasibility of the quantitative prediction method proposed in this research, which also provides a 21% safety margin.

The Loushui River Bridge is a mountainous long-span steel truss arch bridge with high and low arch seats. The design and construction of the bridge follow the principle of minimizing environmental damage and promoting sustainable development. In this article, the mechanical performance of this bridge is investigated experimentally and numerically at both the construction and operation stages. A series of validated finite element models were established for linear and nonlinear analyses by introducing geometric imperfections, geometric nonlinearities, and material nonlinearities. Then, several optimized models based on different types of design are compared with the original structure. The results indicate that the stability of the asymmetric bridge met the design requirements in both the construction and operation stages. However, the lateral stability and stiffness of the asymmetric bridge are weak due to the wind hazard that occurred in its mountain ravine. The out-of-plane instability from the short half-arch is the dominant failure mode, and the weakest area is where the arch ribs intersect with the bridge deck. It can be solved by adding more cross bracings without affecting the clearance above the bridge deck or by improving the material intensity of the arch.

In this paper, a data-driven modeling method for precast concrete (PC) balcony components was proposed to solve the problems of low informatization and the difficult modeling of components at the design stage. Through the analysis of the characteristics of PC balcony components and the combination of modular design methods, the paper designed a data structure for the components and developed a data-driven modeling tool for PC balcony components that can realize the input of structural design data, automatically generating component models. First, this paper introduced the data-driven modeling concept and the modeling process. Second, the PC balcony components in common prefabricated residential projects were analyzed to identify their characteristics. By using a modular design approach, these components were divided and a module dataset was created based on the split modules. Consequently, a data structure for the prefabricated balcony component model was established, wherein both conventional parameters and adaptive parameters between modules were interrelated. Finally, the function of data-driven modeling was achieved by developing a modular design tool on the Revit platform using the C# programming language. The application conducted on a prefabricated building project demonstrated that the software tool and modeling method in this paper effectively improve the level of informatization and modeling efficiency of PC balcony components. The modular design approach was satisfied with the standardization and diversification requirements of balcony components, thereby offering insights for modeling other complex components.

Abstract The restoration of bone defects caused by osteoporosis remains a challenge for surgeons. Strontium ranelate has been applied in preventative treatment approaches due to the biological functions of the trace element strontium (Sr). In this study, we aimed to fabricate bioactive scaffolds through Sr incorporation based on our previously developed modified amino-functional mesoporous bioactive glass (MBG) and to systematically investigate the bioactivity of the resulting scaffold in vitro and in vivo in an osteoporotic rat model. The results suggested that Sr-incorporated amino-functional MBG scaffolds possessed favorable biocompatibility. Moreover, with the incorporation of Sr, osteogenic and angiogenic capacities were upregulated in vitro. The in vivo results showed that the Sr-incorporated amino-functional MBG scaffolds achieved better bone regeneration and vessel formation. Furthermore, bioinformatics analysis indicated that the Sr-incorporated amino-functional MBG scaffolds could reduce reactive oxygen species levels in bone marrow mesenchymal stem cells in the osteoporotic model by activating the cAMP/PKA signaling pathway, thus playing an anti-osteoporosis role while promoting osteogenesis. This study demonstrated the feasibility of incorporating trace elements into scaffolds and provided new insights into biomaterial design for facilitating bone regeneration in the treatment of osteoporosis.

This paper summarizes the important progress in the field of oil and gas production engineering during the “Thirteenth Five-Year Plan” period of China, analyzes the challenges faced by the current oil and gas production engineering in terms of technological adaptability, digital construction, energy-saving and emission reduction, and points out the future development direction. During the “Thirteenth Five-Year Plan” period, series of important progresses have been made in five major technologies, including separated-layer injection, artificial lift, reservoir stimulation, gas well de-watering, and workover, which provide key technical support for continuous potential tapping of mature oilfields and profitable production of new oilfields. Under the current complex international political and economic situation, oil and gas production engineering is facing severe challenges in three aspects: technical difficulty increases in oil and gas production, insignificant improvements in digital transformation, and lack of core technical support for energy-saving and emission reduction. This paper establishes three major strategic directions and implementation paths, including oil stabilization and gas enhancement, digital transformation, and green and low-carbon development. Five key research areas are listed including fine separated-layer injection technology, high efficiency artificial lift technology, fine reservoir stimulation technology, long term gas well de-watering technology and intelligent workover technology, so as to provide engineering technical support for the transformation, upgrading and high-quality development of China’s oil and gas industry.

Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).Design Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).Setting We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measures The primary outcome was a new stroke, LDL-C goal (LDL-C

Abstract Screening of mRNAs and lncRNAs associated with prognosis and immunity of lung adenocarcinoma (LUAD) and used to construct a prognostic risk scoring model (PRS-model) for LUAD. To analyze the differences in tumor immune microenvironment between distinct risk groups of LUAD based on the model classification. The CMap database was also used to screen potential therapeutic compounds for LUAD based on the differential genes between distinct risk groups. he data from the Cancer Genome Atlas (TCGA) database. We divided the transcriptome data into a mRNA subset and a lncRNA subset, and use multiple methods to extract mRNAs and lncRNAs associated with immunity and prognosis. We further integrated the mRNA and lncRNA subsets and the corresponding clinical information, randomly divided them into training and test set according to the ratio of 5:5. Then, we performed the Cox risk proportional analysis and cross-validation on the training set to construct a LUAD risk scoring model. Based on the risk scoring model, patients were divided into distinct risk group. Moreover, we evaluate the prognostic performance of the model from the aspects of Area Under Curve (AUC) analysis, survival difference analysis, and independent prognostic analysis. We analyzed the differences in the expression of immune cells between the distinct risk groups, and also discuss the connection between immune cells and patient survival. Finally, we screened the potential therapeutic compounds of LUAD in the Connectivity Map (CMap) database based on differential gene expression profiles, and verified the compound activity by cytostatic assays. We extracted 26 mRNAs and 74 lncRNAs related to prognosis and immunity by using different screening methods. Two mRNAs (i.e., KLRC3 and RAET1E) and two lncRNAs (i.e., AL590226.1 and LINC00941) and their risk coefficients were finally used to construct the PRS-model. The risk score positions of the training and test set were 1.01056590 and 1.00925190, respectively. The expression of mRNAs involved in model construction differed significantly between the distinct risk population. The one-year ROC areas on the training and test sets were 0.735 and 0.681. There was a significant difference in the survival rate of the two groups of patients. The PRS-model had independent predictive capabilities in both training and test sets. Among them, in the group with low expression of M1 macrophages and resting NK cells, LUAD patients survived longer. In contrast, the monocyte expression up-regulated group survived longer. In the CMap drug screening, three LUAD therapeutic compounds, such as resveratrol, methotrexate, and phenoxybenzamine, scored the highest. In addition, these compounds had significant inhibitory effects on the LUAD A549 cell lines. The LUAD risk score model constructed using the expression of KLRC3, RAET1E, AL590226.1, LINC00941 and their risk coefficients had a good independent prognostic power. The optimal LUAD therapeutic compounds screened in the CMap database: resveratrol, methotrexate and phenoxybenzamine, all showed significant inhibitory effects on LUAD A549 cell lines.

Abstract Chronic wounds represent a major challenge to the present healthcare system. In recent decades, many topical therapies have been investigated for the treatment of chronic wounds, including different types of wound dressings, antimicrobial agents, and cell therapy. Platelet-derived growth factor (PDGF) plays an important role in wound healing and has been approved for treatment of wounds related to diabetes mellitus. However, the high cost and short retention time of PDGF protein have limited its wide application. To overcome this challenge, we designed a PDGF-mimicking peptide by connecting PDGF epitope VRKIEIVRKK and self-assembling motif derived from β-amyloid peptide. The resultant peptide can self-assemble into a fibril-rich network and leads to supramolecular hydrogelation with good stability. The hydrophilic epitope can be exposed on the surface of nanofibrils, which might contribute to the binding and activation of PDGF receptors. The forming hydrogel is able to induce the growth and migration of vascular endothelial cells and promote the formation of vascular branches. In the full-thickness skin wounds of healthy mice, after the application of the hydrogel, the density of neovascularization marked by CD31 was greater than that in the control group on Day 3. Larger collagen deposition and a thicker epidermis were observed on Day 12. These results demonstrate that the hydrogel can stimulate collagen deposition and angiogenesis, enhance skin regeneration, and show an excellent therapeutic effect. Taken together, this work not only provides new insight into the design of bioactive peptides but also offers a promising biomaterial for wound healing.

The COVID-19 pandemic has affected millions of people and posed an unprecedented burden on healthcare systems and economies worldwide since the outbreak of the COVID-19. A considerable number of nations have investigated COVID-19 and proposed a series of prevention and treatment strategies thus far. The pandemic prevention strategies implemented in China have suggested that the spread of COVID-19 can be effectively reduced by restricting large-scale gathering, developing community-scale nucleic acid testing, and conducting epidemiological investigations, whereas sporadic cases have always been identified in numerous places. Currently, there is still no decisive therapy for COVID-19 or related complications. The development of COVID-19 vaccines has raised the hope for mitigating this pandemic based on the intercross immunity induced by COVID-19. Thus far, several types of COVID-19 vaccines have been developed and released to into financial markets. From the perspective of vaccine use in globe, COVID-19 vaccines are beneficial to mitigate the pandemic, whereas the relative adverse events have been reported progressively. This is a review about the development, challenges and prospects of COVID-19 vaccines, and it can provide more insights into all aspects of the vaccines.

Summary: Obesity has become a global epidemic, associated with several chronic complications. The intestinal microbiome is a critical regulator of metabolic homeostasis and obesity. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has putative anti-obesity effects. In this study, we used multi-omics analysis to determine whether empagliflozin regulates metabolism in an obese host through the intestinal microbiota. Compared with obese mice, the empagliflozin-treated mice had a higher species diversity of gut microbiota, characterized by a reduction in the Firmicutes/Bacteroides ratio. Metabolomic analysis unambiguously identified 1,065 small molecules with empagliflozin affecting metabolites mainly enriched in amino acid metabolism, such as tryptophan metabolism. RNA sequencing results showed that immunoglobulin A and peroxisome proliferator-activated receptor signaling pathways in the intestinal immune network were activated after empagliflozin treatment. This integrative analysis highlighted that empagliflozin maintains intestinal homeostasis by modulating gut microbiota diversity and tryptophan metabolism. This will inform the development of therapies for obesity based on host-microbe interactions.

Calycosin, one of small molecules derived from astragalus, has anti-tumor effects in various tumors. However, the effects of calycosin on papillary thyroid cancer (PTC) remain unclear. This study aimed to explore the anti-tumor ability of calycosin on human PTC and its potential mechanisms. The B-CPAP cells were treated with calycosin, then cell proliferation, apoptosis and invasiveness were measured by CCK8 assay, flow cytometry, wound healing and transwell invasion assay, respectively. The cells were also performed by whole transcriptome microarray bioinformatics analysis. Apoptosis and autophagy-related markers or proteins were measured by qRT-PCR or western blot. Sestrin2-mediated AMPK/mTOR pathways were determined by western blot. We found that calycosin inhibited migration and invasion of B-CPAP cells and induced apoptosis (Bax/Bcl-2) and autophagy (LC3II/I, Beclin1) of B-CPAP cells. Differential expressed genes were screened between the calycosin-treated cells and control (524 genes upregulated and 328 genes downregulated). The pathway enrichment suggested that the role of calycosin in B-CPAP cells is closely related to apoptosis-related genes and p70S6 Kinase. Transmission electron microscopy found an increase in autophagosomes in calycosin-treated cells. Sestrin2 in human PTC tissues and B-CPAP cells was lower than in normal thyroid tissues and cells. And the pharmacological effects of calycosin in PTC cells were related to Sestrin2 activation, increased p-AMPK and inhibited p-mTOR and p-p70S6Kinase; these alterations were reversed when silencing Sestrin2. In conclusion, calycosin has an inhibitory effect on PTC via promoting apoptosis and autophagy through the Sestrin2/AMPK/mTOR pathway.

Efficient air filter element is a key component to prevent erosion, corrosion and solids precipitation in the flow path of gas turbine. However, the performance of the air filter element is significantly reduced in high humidity environment, which seriously affects the safe operation of gas turbine. Herein, the filtration performance of four types of filter element made of F9 filter materials was tested. By comparing the tensile strength of the filter materials under different conditions, the change of pressure drop and efficiency of the filter element was measured in the conditions with different droplet mass concentration. The results show that the moisture resistance of the filter material mainly depends on the fiber composition. The synthetic fiber can effectively reduce the water absorption rate of the filter materials, and the filter element made of materials with low water absorption rate has a stronger capability to maintain its original performance with the influence of water spray. The research results could provide technical reference for the operation and maintenance of gas turbine inlet filtration system and the development of efficient moisture-resistant filter elements.

Bone defect repair and fracture healing are critical challenges in clinical treatments. Bioactive natural compounds are potential resources for medications for osteogenic effects. We have identified icariin, the effective ingredient of Epimedium pubescens, to promote osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and repair bone defects. To explore more natural compounds with the potential modality for bone repair, in the present study, we employed an icariin-induced gene expression pattern as an osteogenic model and screened the Connectivity Map database for small molecules with gene expression signatures similar to this model. We verified the effectiveness of this molecule docking approach by introducing hydroxycholesterol, the second highest score of the similarity to icariin, into the osteoinductive experiments in vitro and demonstrated its excellent osteogenic effect on BMSCs compared with a BMP-2-positive control group. Based on the compatible result of hydroxycholesterol, subsequently, ginsenoside Rb1 was chosen as the most drug-like natural compound among the molecule docking results from icariin. Finally, ginsenoside Rb1 was demonstrated to promote the expression of osteoblastic genes and ALP activity in vitro and repair the calvarial defect of rats in vivo. The study aimed to provide diverse choices for clinical application in bone repair and functional regeneration.

Empagliflozin (EMPA) is a novel sodium-glucose cotransporter 2 inhibitor (SGLT2i) that produces protective cardiovascular-renal outcomes in patients with diabetes. However, the effects of EMPA on obesity-related kidney disease have not been determined. The heme oxygenase-1 (HO-1)–adiponectin axis is an essential antioxidant system with anti-apoptotic and anti-inflammatory properties. This study explored whether EMPA improves obesity-related kidney disease through regulation of the renal HO-1-mediated adiponectin axis. C57BL/6J mice were assigned to control, high-fat diet (HFD) groups, and EMPA (10 mg/kg) groups. HFD mice showed metabolic abnormality and renal injury, including increased urinary albumin excretion, morphologic changes, and lipid accumulation. EMPA treatment improved metabolic disorders and attenuated lipotoxicity-induced renal injury. Furthermore, EMPA treatment ameliorated renal NLRP3 inflammasome activity and upregulated the HO-1–adiponectin axis. Our findings indicate that EMPA improves obesity-related kidney disease through reduction of NLRP3 inflammasome activity and upregulation of the HO-1–adiponectin axis, suggesting a novel mechanism for SGLT2i-mediated renal protection in obesity.

Background Small single subcortical infarction (SSSI) may be classified as parent artery disease-related or only branch involved according to the stenosis of parent artery. The study aimed to evaluate short-term and long-term prognoses and the effectiveness of antiplatelet therapy in SSSI.Methods We prospectively enrolled 2890 patients with SSSI from the Third China National Stroke Registry (CNSR-III) database from August 2015 to March 2018. We assessed clinical outcomes and antiplatelet treatment effects in patients with SSSI with and without parent artery stenosis (PAS) identified by magnetic resonance angiography.Results Among 2890 patients with SSSI in the perforator territory of the middle cerebral artery and the basilar artery, there were 680 (23.53%) patients with PAS and 2210 (76.47%) patients without PAS, respectively. After adjusting for potential confounders, the PAS group had a greater initial stroke severity (OR 1.262, 95% CI 1.058 to 1.505; p=0.0097) and a higher risk of ischaemic stroke recurrence at 3 months (OR 2.266, 95% CI 1.631 to 3.149; p

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Dysregulation of both coding and long noncoding RNAs (lncRNAs) plays crucial role in the pathogenesis and development of the disease. In this study, we identified a profile of dysregulated RNAs using datasets from a public database. By incorporating all interactions between different RNAs, a competing endogenous RNA network was established to further illustrate the regulatory roles of noncoding miRNAs and lncRNAs. Moreover, a functional analysis showed that NAFLD is more closely associated with certain biological processes and pathways. Altogether, these results provide a helpful perspective on NAFLD and may assist future diagnosis and treatment of the disease.

BackgroundIt is estimated that 35% of gastric cancer patients appear with synchronous distant metastases—the vast majority of patients presenting with metastatic hepatic disease. How to choose the most appropriate drugs or regimens is crucial to improve the prognosis of patients. We conducted this retrospective cohort analysis to evaluate the efficacy of OncoVee™-MiniPDX-guided treatment for these patients.MethodsGastric cancer patients with liver metastases (GCLM) were enrolled. Patients were divided into MiniPDX and control group according to their wishes. In the observation group, the OncoVee™-MiniPDX model was conducted to screen the most sensitive drug or regimens to determine the clinical administration. Meanwhile, patients were treated with regular medications in the control group according to the guidelines without the MiniPDX model. The primary endpoint was overall survival (OS), and the secondary outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS).ResultsA total of 68 patients with GCLM were included, with the observation and control groups of 21 and 47 patients, respectively. The baseline characteristics of patients were balanced between these two groups. MiniPDX drug sensitivity tests were associated with the increased use of targeted drugs when compared with the control group (33.3 vs. 0%, p=0.032). Median OS was estimated to be 9.4 (95% CI, 7.9–11.2) months and 7.9 (95% CI, 7.2–8.7) months in the observation and control group, respectively. Both univariate (control group vs. MiniPDX group: HR=2.586, 95% CI= 1.362–4.908, p=0.004) and multivariate regression analyses (Control group vs. MiniPDX group: adjusted HR (aHR)=4.288, 95% CI= 1.452–12.671, p=0.008) showed the superiority of the observation group on OS. Similarly, MiniPDX-based regiments significantly improve the PFS of these cases (median PFS 6.7 months vs. 4.2 months, aHR=2.773, 95% CI=1.532–3.983, p=0.029). ORR and DCR were also improved in MiniPDX group comparing with control group (ORR, 57.14 vs. 25.53%, p=0.029; DCR: 85.71 vs. 68.08%, p=0.035).ConclusionOncoVee™-MiniPDX model, which was used to select drugs to guide antitumor treatment, was promising to prolong survival and improve the response rate of patients with GCLM. Further well-designed studies are needed to confirm the clinical benefits of MiniPDX.

Ferroptosis is a novel type of iron- and ROS-dependent cell death and is involved in various diseases. LncRNAs are involved and play important roles in the occurrence and development of several cancers. However, researches about the role of ferroptosis-related lncRNAs in glioma are relatively rare. Here, we identified nine ferroptosis-related lncRNAs and then constructed a prognostic model by the LASSO and Cox analysis. The model could predict overall survival with high sensitivity and specificity according to ROC curves. In addition, the cell cycle, p53 signaling, apoptosis, and oxidative phosphorylation pathways were obviously enriched in the pathogenesis of glioma by gene set enrichment analysis. A nomogram was constructed by integrating several independent prognostic clinicopathological features, and it could provide a valuable predictive tool for overall survival. Furthermore, a strong correlation between these nine lncRNAs and immunotherapy was found. Glioma patients in the high-risk group had higher TMB using somatic mutation data, different immune infiltration, and higher expression of immune checkpoints, indicating these patients might benefit from immune checkpoint inhibitor therapy. In summary, these nine ferroptosis-related lncRNAs were promising biomarkers for predicting overall survival and guiding immunotherapy or future immune checkpoint inhibitor development for glioma patients.

The in situ conversion process (ICP) is a retorting method pyrolyzing the kerogen in shale into oil and gas products, which shows great potential to promote the recovery of oil shale resources. In this work, a thermo-hydro-chemical-coupled model for the in situ conversion process is established, considering the temperature dependence of key properties and the transverse isotropy caused by the layered characteristics of oil shale. Based on the proposed model, a series of simulations is conducted to evaluate the production performance of the in situ conversion process of oil shale reservoirs. The results indicate that energy efficiency reaches a maximum of 2.7 around the fifth year of the heating process, indicating the feasibility of in situ conversion technology. Furthermore, the sensitivity analysis shows that the heating temperature should be higher than 300 °C to avoid the energy output being less than the energy input, and the oil/gas ratio decreases with increasing heating temperature. Moreover, thermal conductivity is positively with production while heat capacity is negatively correlated, and the energy efficiency decreases with increasing thermal conductivity and matrix heat capacity. Finally, the heating period should be no longer than 4 years to maximize the heating efficiency.

Empagliflozin is a novel type of sodium-glucose cotransporter two inhibitor with diverse beneficial effects in the treatment of nonalcoholic fatty liver disease (NAFLD). Although empagliflozin impacts NAFLD by regulating lipid metabolism, the underlying mechanism has not been fully elucidated. In this study, we investigated transcriptional regulation pathways affected by empagliflozin in a mouse model of NAFLD. In this study, NAFLD was established in male C57BL/6J mice by administration of a high-fat diet; it was then treated with empagliflozin and whole transcriptome analysis was conducted. Gene expression levels detected by transcriptome analysis were then verified by quantitative real-time polymerase chain reaction, protein levels detected by Western Blot. Differential expression genes screened from RNA-Seq data were enriched in lipid metabolism and synthesis. The Gene Set Enrichment Analysis (GSEA) results showed decreased lipid synthesis and improved lipid metabolism. Empagliflozin improved NAFLD through enhanced triglyceride transfer, triglyceride lipolysis and microsomal mitochondrial β-oxidation. This study provides new insights concerning the mechanisms by which sodium-glucose cotransporter two inhibitors impact NAFLD, particularly in terms of liver lipid metabolism. The lipid metabolism-related genes identified in this experiment provide robust evidence for further analyses of the mechanism by which empagliflozin impacts NAFLD.

As an important type of unconventional hydrocarbon, tight sandstone oil has great present and future resource potential. Reservoir quality evaluation is the basis of tight sandstone oil development. A comprehensive evaluation approach based on the gray correlation algorithm is established to effectively assess tight sandstone reservoir quality. Seven tight sandstone samples from the Chang 6 reservoir in the W area of the AS oilfield in the Ordos Basin are employed. First, the petrological and physical characteristics of the study area reservoir are briefly discussed through thin section observations, electron microscopy analysis, core physical property tests, and whole-rock and clay mineral content experiments. Second, the pore type, throat type and pore and throat combination characteristics are described from casting thin sections and scanning electron microscopy. Third, high-pressure mercury injection and nitrogen adsorption experiments are optimized to evaluate the characteristic parameters of pore throat distribution, micro- and nanopore throat frequency, permeability contribution and volume continuous distribution characteristics to quantitatively characterize the reservoir micro- and nanopores and throats. Then, the effective pore throat frequency specific gravity parameter of movable oil and the irreducible oil pore throat volume specific gravity parameter are introduced and combined with the reservoir physical properties, multipoint Brunauer-Emmett-Teller (BET) specific surface area, displacement pressure, maximum mercury saturation and mercury withdrawal efficiency parameters as the basic parameters for evaluation of tight sandstone reservoir quality. Finally, the weight coefficient of each parameter is calculated by the gray correlation method, and a reservoir comprehensive evaluation indicator (RCEI) is designed. The results show that the study area is dominated by types II and III tight sandstone reservoirs. In addition, the research method in this paper can be further extended to the evaluation of shale gas and other unconventional reservoirs after appropriate modification.

Abdominal aortic aneurysms (AAAs) are typically asymptomatic, and there is a high mortality rate associated with aneurysm rupture. AAA pathogenesis involves extracellular matrix degradation, vascular smooth muscle cell phenotype switching, inflammation, and oxidative stress. There is increasing evidence of excessive adipocyte accumulation in ruptured AAA walls. These excessive numbers of adipocytes in the vascular wall have been closely linked with AAA progression. Perivascular adipose tissue (PVAT), a unique type of adipose tissue, can be involved in adipocyte accumulation in the AAA wall. PVAT produces various chemokines and adipocytokines around vessels to maintain vascular homeostasis through paracrine and autocrine mechanisms in normal physiological conditions. Nevertheless, PVAT loses its normal function and promotes the progression of vascular diseases in pathological conditions. There is evidence of significantly reduced AAA diameter in vessel walls of removed PVAT. There is a need to highlight the critical roles of cytokines, cells, and microRNA derived from PVAT in the regulation of AAA development. PVAT may constitute an important therapeutic target for the prevention and treatment of AAAs. In this review, we discuss the relationship between PVAT and AAA development; we also highlight the potential for PVAT-derived factors to serve as a therapeutic target in the treatment of AAAs.

Abstract Background To compare the microbiological culture within endotracheal aspirate specimens (ETAs) and endotracheal tube specimens (ETTs) in patients undergoing mechanical ventilation (MV) by statistical tools. Method ETAs and ETTs from a total number of 81 patients, who were undergoing MV at the intensive care unit (ICU) of Jiading Central Hospital Affiliated Shanghai University of Medicine & Health Sciences from September 1st, 2017 to August 31st, 2018, were collected for microbiological culture analysis. Correlation of ETAs and ETTs cultures were obtained by Spear-men correlation analysis, while the consistency of the two specimens was determined by Kappa analysis and principal component analysis (PCA). Results Microbiological culture from both ETAs and ETTs showed that Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae were the main pathogens, with Spear-man correlation coefficients of 0.676, 0.951, 0.730 and 0.687 respectively (all P

Cerebral stroke is a fatal disease with increasing incidence. The study was to investigate the role and mechanism of Histone deacetylase 6 (HDAC6) on experimental stroke-induced brain injury. The recombinant shRNA-HDAC6 or scramble shRNA lentivirus was transfected to ICR mice. Then, the ischemia/reperfusion injury (I/RI) mice were constructed using middle cerebral artery occlusion (MCAO) method. Brain TTC staining was used to determine infarct areas. Serum levels of oxidative stress-related factors were detected by enzyme linked immunosorbnent assay (ELISA). Realtime-qPCR (RT-qPCR) and Western blot were used to respectively detect mRNA and protein levels. HDAC6 was up-regulated in brain I/RI mice (MCAO group), and down-regulated again in MCAO mice transfected with shRNA-HDAC6 (MCAO + shRNA group). The infarct area of the MCAO mice was increased, neurological scores were higher, and serum protein levels of 3-NT, 4-HNE and 8-OHdG were higher. HDAC6 interference attenuated above effects. Though protein levels of Nrf2 and HO-1 in cytoplasm increased slightly in MCAO group, they increased significantly by HDAC6 interference. The protein levels of Nrf2 in cytoblast decreased significantly in MCAO group, and increased markedly by HDAC6 interference. HDAC6 interference protected mice against experimental stroke-induced brain injury via Nrf2/HO-1 pathway.