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Abstract The abnormal structure of tumor vascular seriously hinders the delivery and deep penetration of drug in tumor therapy. Herein, an integrated and tumor microenvironment (TME)-responsive nanocarrier is designed, which can dilate vessle and improve the drug penetration by in situ releasing nitric oxide (NO). Briefly, S-nitroso-glutathione (GSNO) and curcumin (Cur) were encapsulatd into the Cu-doped zeolite imidazole framework-8 (Cu-ZIF-8) and modified with hyaluronic acid. The nanocarrier degradation in the weakly acidic of TME releases Cu2+, then deplete overexpressed intratumourally glutathione and transformed into Cu+, thus disrupting the balance between nicotinamide adenine dinucleotide phosphate and flavin adenine dinucleotide (NADPH/FAD) during the metabolism homeostasis of tumor. The Cu+ can generate highly toxic hydroxyl radical through the Fenton-like reaction, enhancing the chemodynamic therapeutic effect. In addition, Cu+ also decomposes GSNO to release NO by ionic reduction, leading to vasodilation and increased vascular permeability, significantly promoting the deep penetration of Cur in tumor. Afterwards, the orderly operation of cell cycle is disrupted and arrested in the S-phase to induce tumor cell apoptosis. Deep-hypothermia potentiated 2D/3D fluorescence imaging demonstrated nanocarrier regulated endogenous metabolism homeostasis of tumor. The cascade-catalysed multifunctional nanocarrier provides an approach to treat orthotopic tumor.

Objectives: With the depletion of easily recoverable oil reservoirs, the focus of oil and gas exploration and development in China has shifted to "two deeps and non-conventional" oil and gas fields. This transformation is not only accompanied by a significant increase in well depth and more complex formation challenges but also presents more stringent requirements for the design and construction of drilling engineering, which directly leads to a significant extension of the drilling cycle. The length of the drilling cycle is a key factor in determining drilling costs. Therefore, for a long time, scholars have been committed to improving the mechanical penetration rate and the durability of polycrystalline diamond composite (PDC) bits. The main purpose of this study is to analyze geological characteristics in depth, accurately match and optimize the design of special-shaped teeth in PDC drill bits, in order to significantly reduce the risk of drill bit failure and greatly improve mechanical drilling speed and footage. Given the wide application of PDC bits in hard rock drilling and their key impact on the cost and efficiency of drilling operations, this study focuses on the design and optimization of ridge-shaped PDC teeth, aiming to explore more suitable tooth structures for specific geological conditions through scientific testing and comparative analysis. This will promote innovation and efficiency improvements in drilling technology. Methods: Based on round teeth, the wear resistance, impact resistance, and rock-breaking effect of three types of ridge-shaped teeth were systematically tested. First, the wear resistance and impact resistance of three typical ridge-shaped PDC teeth—namely the 165 axe-shaped, 135 axe-shaped, and three-edged cutters—were tested to quantitatively evaluate their mechanical properties. Subsequently, granite was selected as the representative rock sample, and the single-tooth cutting tests were conducted with three different penetration depths to simulate the cutting effect under various drilling pressures during actual drilling. Additionally, a full-size bit simulation drilling test was designed to evaluate the drilling performance of each tooth shape under different pressures, and the data were compared with those of round teeth. This series of tests aimed to fully reveal the advantages and disadvantages of ridge-shaped PDC teeth in terms of wear resistance, impact resistance, and rock-breaking effectiveness. Results: The test results show that the three ridge-shaped PDC cutters significantly outperform the round teeth in terms of wear resistance. The 135 axe-shaped cutter, with the smallest ridge angle, exhibited the greatest improvement in wear resistance, indicating that the ridge design enhances the durability of PDC cutters and bits. In terms of impact resistance, the 165 axe-shaped cutter and the three-edged cutter performed excellently and could effectively withstand high impact loads, while the 135 axe-shaped cutter had relatively weaker impact resistance due to insufficient support at the impact point. Further analysis of the cutting force data revealed that the tangential force and normal forces of ridge-shaped cutters were lower than those of round cutters at the same cutting depth. The smaller the ridge angle, the smaller the cutting force, which indicates that the ridge design helps reduce cutting resistance and improve drilling efficiency. The full-size drill bit simulation drilling test results showed that the 135 axe-shaped cutter achieved the fastest mechanical drilling speed and is suitable for high-pressure operations. The three-edged cutter performed better in the low-pressure range (≤ 20 kN), while the round teeth had the slowest drilling speed and a lower suitable drilling pressure range. Additionally, the variation in ridge tooth angle not only affects the impact resistance but also directly influences the rock-breaking effect by altering the stress distribution within the rock. Conclusions: Through systematic testing and comparative analysis, this study has verified the significant advantages of ridge-shaped PDC cutters in improving drilling efficiency and reducing the risk of drill bit failure. Specifically, the ridge design effectively enhances the wear resistance and impact resistance of the drill bit while reducing cutting force and increasing mechanical drilling speed. The performance differences of the various ridge-shaped cutters under different drilling pressure conditions provide a scientific basis for the flexible selection of drill bit types based on formation conditions during drilling operations. In the future, further optimization of ridge-shaped PDC cutter designs, especially for specific formation conditions, will be an important direction for improving mechanical drilling speeds and reducing operational costs.

The asymptotic behavior for a heriditary recursion$ \begin{equation*} x_1>a \, \, \text{and} \, \, x_{n+1} = \frac{1}{n^s}\sum\limits_{k = 1}^nf\left(\frac{x_k}k\right)\text{ for every }n\geq1 \end{equation*} $is studied, where $ f $ is decreasing, continuous on $ (a, \infty) $ ($ a < 0 $), and twice differentiable at $ 0 $. The result has been known for the case $ s = 1 $. This paper analyzes the case $ s > 1 $. We obtain an asymptotic sequence that is quite different from the case $ s = 1 $. Some examples and applications are provided.

Abstract Multiple sclerosis (MS) is a leading cause of non-traumatic disability in young adults. The highly dynamic nature of MS lesions has made them difficult to study using traditional histopathology due to the specificity of current stains. This requires numerous stains to track and study demyelinating activity in MS. Thus, we utilized Fourier transform infrared (FTIR) spectroscopy to generate holistic biomolecular profiles of demyelinating activities in MS brain tissue. Multivariate analysis can differentiate MS tissue from controls. Analysis of the absorbance spectra shows profound reductions of lipids, proteins, and phosphate in white matter lesions. Changes in unsaturated lipids and lipid chain length indicate oxidative damage in MS brain tissue. Altered lipid and protein structures suggest changes in MS membrane structure and organization. Unique carbohydrate signatures are seen in MS tissue compared to controls, indicating altered metabolic activities. Cortical lesions had increased olefinic lipid content and abnormal membrane structure in normal appearing MS cortex compared to controls. Our results suggest that FTIR spectroscopy can further our understanding of lesion evolution and disease mechanisms in MS paving the way towards improved diagnosis, prognosis, and development of novel therapeutics.

Bubble dynamics is paramount in comprehending the heat transfer mechanisms of flow boiling in the microchannel within ultrasonic field, which is regarded as a promising method to confront challenges of thermal management posed by microelectronic devices. Nevertheless, the impact of ultrasound on bubble behaviors and its underlying mechanisms remain largely unexplored. This study first delves into the effect of ultrasonic parameters on bubble dynamic behaviors and associated mechanisms, subsequently further analyzing the forces acting on bubbles through the constructed force model. The findings suggest that although growth force serves as the significant resistance, the primary Bjerknes force dominates the rapid detachment of bubbles. The secondary Bjerknes force results in the bubble only sliding along the bottom wall rather than lifting off. Furthermore, the elevated ultrasonic pressure amplitude resulting from augmenting ultrasonic power induces a substantial increase in the critical detachment diameter and growth rate by 55.49 % and 59.42 %, respectively. The enhanced primary Bjerknes force, attributed to the rise in ultrasonic frequency, leads to a 71.42 % increase in sliding velocity and a 46.45 % reduction in growth time. The positive impacts arising from ultrasonic power and frequency are anticipated to notably enhance the thermal performance of microchannels. Besides, surface tension acts as the resistance and diminishes slightly with an augmentation of the boiling number, resulting in a moderate variation in sliding velocity and growth time.

Background Microbial colonisation in infants is initially dependent on the mother and is affected by the mode of delivery. Understanding these impacts is crucial as the early-life gut microbiota plays a vital role in immune development, metabolism, and overall health. Early-life infant gut microbiota is diverse among populations and geographic origins. However, in this context, only a few studies have explored the impact of the mode of delivery on the intestinal microbiome in children in Guangzhou, China. Therefore, this study aimed to investigate the influence of birth mode on the intestinal microbiota of healthy infants in Guangzhou, China.Methods Faecal samples were collected once from 20 healthy full-term infants aged 1–6 months, delivered via either caesarean section (CS) or vaginal delivery (VD), post-enrolment. The intestinal microbiota were characterised using full-length 16S rRNA gene sequencing. Bacterial quantity and community composition were compared between the two groups.Results No significant differences in gut bacterial diversity and richness were observed between the CS and VD groups. The Pseudomonadota phylum (44.15 ± 33.05% vs 15.62 ± 15.60%, p = 0.028) and Enterobacteriaceae family (44.00 ± 33.11% vs 15.31 ± 15.47%, p = 0.028) were more abundant in the CS group than in the VD group. The VD group exhibited a higher abundance of the Bacillota phylum (40.51 ± 32.77% vs 75.57 ± 27.83%, p = 0.019),Conclusions The early stage of intestinal bacterial colonisation was altered in the CS group as compared with the VD group. Our findings provide evidence that CS has the potential to disrupt the maturation of intestinal microbial communities in infants by influencing the colonisation of specific microorganisms. Further comprehensive studies that consider geographical locations are necessary to elucidate the progression of microbiota in infants born via different delivery modes.

Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have revolutionized the treatment of acute promyelocytic leukemia (APL). However, the management of high-risk APL has not been conclusively established. The optimal dosage of anthracycline in the induction has long been debated when ATO is added. Objectives: To explore the management of high-risk APL regarding the optimal dosage of anthracycline in the induction and the predicators of prognosis. Design: This was a retrospective study in the real-world setting. Methods: High-risk APL patients defined as white blood cell (WBC) greater than 10 × 10 9 /L who received ATO-based induction regimens were included. Data on clinical characteristics, treatment regimens, and prognosis including early death (ED) and overall survival (OS) were collected from medical records. Risk factors of ED and OS were analyzed. Results: This research included a total of 130 participants. Fifty (38.5%) patients received ATO+ATRA dual induction plus standard-dose anthracycline (ATO + ATRA + stDNR). Fifty-nine (45.4%) patients received ATO + ATRA with consecutive low-dose anthracycline (ATO + ATRA + ldDNR). Twenty-one (16.2%) patients were treated with ATO and various chemotherapies (ATO + others). Compared with the other two groups, the ATO + ATRA + stDNR group had the lowest ED rate of 4.0% (10.2% and 52.4%, respectively; p

LN is a serious complication of systemic lupus erythematosus (SLE), affecting up to 60% of patients with SLE and may lead to end-stage renal disease (ESRD). Macrophages play multifaceted roles in the pathogenesis of LN, including clearance of immune complexes, antigen presentation, regulation of inflammation, and tissue repair. Macrophages are abundant in the glomeruli and tubulointerstitium of LN patients and are positively correlated with serum creatinine levels and the severity of renal pathology. It has been shown that the infiltration of macrophages is closely associated with several clinical indicators, such as serum creatinine and complement C3 levels, anti-dsDNA antibody titers, Austin score, interstitial fibrosis and renal tubular atrophy. Moreover, cytokines expressed by macrophages were upregulated at LN onset and downregulated after remission, suggesting that macrophages may serve as markers of LN pathogenesis and remission. Therapies targeting macrophages have been shown to alleviate LN. There are two main types of macrophages in the kidney: kidney-resident macrophages (KRMs) and monocyte-derived macrophages (MDMs). KRMs and MDMs play different pathological roles in LN, with KRMs promoting leukocyte recruitment at sites of inflammation by expressing monocyte chemokines, while MDMs may exacerbate autoimmune responses by presenting immune complex antigens. Macrophages exhibit high plasticity and can differentiate into various phenotypes in response to distinct environmental stimuli. M1 (proinflammatory) macrophages are linked to the progression of active SLE, whereas the M2 (anti-inflammatory) phenotype is observed during the remission phase of LN. The polarization of macrophages in LN can be manipulated through multiple pathways, such as the modulation of signaling cascades including TLR 2/1, S1P, ERS, metabolic reprogramming, and HMGB1. This paper provides a comprehensive overview of the role of macrophages in the progression of lupus nephritis (LN), and elucidates how these cells and their secretory products function as indicators and therapeutic targets for the disease in the context of diagnosis and treatment of LN.

ABSTRACT The objective of this study was to establish a more sensitive and specific diagnostic method for detecting plasma BK polyomavirus (BKPyV) DNA load in patients after renal transplantation using droplet digital polymerase chain reaction (ddPCR) and to validate the methodology. The linear range, lower limit of detection, accuracy, precision, and specificity of the detection system were evaluated by using the WHO BKPyV standard (7.2 log10 IU/mL) as a reference, in accordance with the relevant documents of the Clinical and Laboratory Standards Institute. Plasma samples were collected from 74 renal transplantation patients with urinary BKPyV-DNA levels exceeding 7 log10 copies/mL. Quantitative PCR (qPCR) and ddPCR were performed, and their diagnostic efficacy for BKPyV-DNA in the diagnosis of BK polyomavirus-associated nephropathy was evaluated using a receiver operating characteristic (ROC) curve. The coefficients of variation for the repeated detection of BKPyV standard DNA were 2.55 and 4.71 at concentrations of 6.2 and 3.2 log10 IU/mL, respectively. The linear range was 2.2–6.2 log10 IU/mL, and the lowest detection limit was 100 IU/mL. By utilizing histopathological examination of renal biopsy as the gold standard for BKPyV diagnosis, the area under the ROC curve of 74 post-transplantation plasma samples detected by the ddPCR system was found to be 0.875 (95% CI: 0.797–0.953, P < 0.01). The optimal threshold was 512.86 copies/mL, with a sensitivity of 90.0% and a specificity of 67.6%. In comparison, the area under the ROC curve for qPCR was 0.668 (95% CI: 0.583–0.752, P < 0.01), with an optimal threshold of 11,481.54 copies/mL, a sensitivity of 35.0%, and a specificity of 100.0%. Pairwise comparison (Delong test) of the ROC curves of the two systems showed a significant difference in the area under the curve, with a difference of 0.207 and a P-value

Some properties of the constant in asymptotic expansion of iterates of a cubic function were investigated. This paper analyzed the monotonicity, differentiability of the constant with respect to the initial value and the functional equation that is satisfied.

Abstract Background Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis. Methods The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF+/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague–Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair. Results The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF+/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects. Conclusion NGF+/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF+/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.

Abstract Binding of Staphylococcus aureus protein A (SPA) to osteoblasts induces apoptosis and inhibits bone formation. Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into bone, fat and cartilage. Therefore, it was important to analyze the molecular mechanism of SPA on osteogenic differentiation. We introduced transcript sequence data to screen out differentially expressed genes (DEGs) related to SPA-interfered BMSC. Protein–protein interaction (PPI) network of DEGs was established to screen biomarkers associated with SPA-interfered BMSC. Receiver operating characteristic (ROC) curve was plotted to evaluate the ability of biomarkers to discriminate between two groups of samples. Finally, we performed GSEA and regulatory analysis based on biomarkers. We identified 321 DEGs. Subsequently, 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap and Kif14) were identified by hubba algorithm in PPI. ROC analysis showed that six biomarkers could clearly discriminate between normal differentiated and SPA-interfered BMSC. Moreover, we found that these biomarkers were mainly enriched in the pyrimidine metabolism pathway. We also constructed '71 circRNAs-14 miRNAs-5 mRNAs' and '10 lncRNAs-5 miRNAs-2 mRNAs' networks. Kntc1 and Asf1b genes were associated with rno-miR-3571. Nek2 and Asf1b genes were associated with rno-miR-497-5p. Finally, we found significantly lower expression of six biomarkers in the SPA-interfered group compared to the normal group by RT-qPCR. Overall, we obtained 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap, and Kif14) related to SPA-interfered BMSC, which provided a theoretical basis to explore the key factors of SPA affecting osteogenic differentiation.

Abstract The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor that affects cellular phenotypes by modulating phagocytosis and metabolism, promoting cell survival, and counteracting inflammation. Its role in renal injury, in particular, unilateral ureteral obstruction (UUO) or ischemia-reperfusion injury (IRI)-induced renal injury remains unclear. In our study, WT and Trem2 −/− mice were employed to evaluate the role of TREM2 in renal macrophage infiltration and tissue injury after UUO. Bone marrow-derived macrophages (BMDM) from both mouse genotypes were cultured and polarized for in vitro experiments. Next, the effects of TREM2 on renal injury and macrophage polarization in IRI mice were also explored. We found that TREM2 expression was upregulated in the obstructed kidneys. TREM2 deficiency exacerbated renal inflammation and fibrosis 3 and 7 days after UUO, in association with reduced macrophage infiltration. Trem2 −/− BMDM exhibited increased apoptosis and poorer survival compared with WT BMDM. Meanwhile, TREM2 deficiency augmented M1 and M2 polarization after UUO. Consistent with the in vivo observations, TREM2 deficiency led to increased polarization of BMDM towards the M1 proinflammatory phenotype. Mechanistically, TREM2 deficiency promoted M1 and M2 polarization via the JAK-STAT pathway in the presence of TGF-β1, thereby affecting cell survival by regulating mTOR signaling. Furthermore, cyclocreatine supplementation alleviated cell death caused by TREM2 deficiency. Additionally, we found that TREM2 deficiency promoted renal injury, fibrosis, and macrophage polarization in IRI mice. The current data suggest that TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway. These findings have implications for the role of TREM2 in the regulation of renal injury that justify further evaluation.

Abstract Background Osteocytes are critical mechanosensory cells in bone, and mechanically stimulated osteocytes produce exosomes that can induce osteogenesis. MicroRNAs (miRNAs) are important constituents of exosomes, and some miRNAs in osteocytes regulate osteogenic differentiation; previous studies have indicated that some differentially expressed miRNAs in mechanically strained osteocytes likely influence osteoblastic differentiation. Therefore, screening and selection of miRNAs that regulate osteogenic differentiation in exosomes of mechanically stimulated osteocytes are important. Results A mechanical tensile strain of 2500 με at 0.5 Hz 1 h per day for 3 days, elevated prostaglandin E2 (PGE2) and insulin-like growth factor-1 (IGF-1) levels and nitric oxide synthase (NOS) activity of MLO-Y4 osteocytes, and promoted osteogenic differentiation of MC3T3-E1 osteoblasts. Fourteen miRNAs differentially expressed only in MLO-Y4 osteocytes which were stimulated with mechanical tensile strain, were screened, and the miRNAs related to osteogenesis were identified. Four differentially expressed miRNAs (miR-1930-3p, miR-3110-5p, miR-3090-3p, and miR-3058-3p) were found only in mechanically strained osteocytes, and the four miRNAs, eight targeted mRNAs which were differentially expressed only in mechanically strained osteoblasts, were also identified. In addition, the mechanically strained osteocyte-derived exosomes promoted the osteoblastic differentiation of MC3T3-E1 cells in vitro, the exosomes were internalized by osteoblasts, and the up-regulated miR-3110-5p and miR-3058-3p in mechanically strained osteocytes, were both increased in the exosomes, which was verified via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Conclusions In osteocytes, a mechanical tensile strain of 2500 με at 0.5 Hz induced the fourteen differentially expressed miRNAs which probably were in exosomes of osteocytes and involved in osteogenesis. The mechanically strained osteocyte-derived exosomes which contained increased miR-3110-5p and miR-3058-3p (two of the 14 miRNAs), promoted osteoblastic differentiation.

ABSTRACT Purpose: Artesunate (ART) has been implicated in regulating the many processes of liver injury, but its roles in liver regeneration still need to be illustrated. Methods: In the present study, ART was used to pretreat hepatocyte cell line NCTC1469 to study the effect of ART on hepatocyte proliferation in vitro. Furthermore, the potency of ART as a regimen to promote liver regeneration and restore liver function was evaluated following partial hepatectomy (PH) on C57BL/6 mice. Results: ART concentration-dependently promoted hepatocyte proliferation and reduced apoptosis. Cell cycle and Ki-67 immunohistochemical analyses demonstrated that ART supplementation promoted the proliferation of hepatocytes and accelerated liver regeneration. Our results provided evidence that ART improved liver function in a dose-dependent manner, as indicated by decreased serum alanine aminotransferase, aspartate aminotransferase, and increased albumin, and hepatocyte growth factor levels in PH mice. Meanwhile, ART promoted the PI3K/Akt/mTOR signaling in NCTC1469 cells and liver tissue of PH mice. In addition, PI3K inhibitor LY294002 blocked the promotion effect of ART on hepatocyte proliferation and cell cycle progression. Conclusion: ART promoted hepatocyte proliferation via activation of the PI3K/Akt/mTOR pathway, which was beneficial to liver regeneration of PH-induced liver injury.

Abstract Acute kidney injury (AKI) presents as a condition marked by a sudden and rapid decrease in kidney function over a short timeframe, resulting from diverse causes. As a transcription factor, PR domain‐containing 16 (PRDM16), has recently been implicated in brown fat biogenesis and heart diseases. Our recent works indicated that PRDM16 could suppress the occurrence of renal interstitial fibrosis in diabetic kidney disorder. Nonetheless, the effect and regulatory mechanism of PRDM16 in AKI remain elusive. Our study demonstrated that PRDM16 inhibited apoptosis induced by ischemic/reperfusion (I/R) in BUMPT (Boston University mouse kidney proximal tubular) cells and HK‐2(Human Kidney‐2) cells. Mechanistically, PRDM16 not only bound to the promoter region of S100 Calcium Binding Protein A6 (S100A6)and upregulated its expression but also interacted with its amino acids 945–949, 957–960, and 981–984 to suppress the p38MAPK and JNK axes via inhibition of PKC‐η activity and mitochondrial reactive oxygen species (ROS) production. Furthermore, cisplatin‐ and I/R‐stimulated AKI progression were ameliorated in PRDM16 proximal‐tubule‐specific knockin mice, whereas exacerbated in PRDM16 knockout proximal‐tubule‐specific mice). Moreover, we observed that formononetin ameliorated I/R‐ and cisplatin‐triggered AKI progression in mice. Taken together, these findings reveal a novel self‐protective mechanism in AKI, whereby PRDM16 regulates the S100A6/PKC‐η/ROS/p38MAPK and JNK pathways to inhibit AKI progression.

The texture of human skin is influenced by both external and internal factors, and changes in wrinkles can most directly reflect the state of the skin. Skin roughness is primarily used to quantify the wrinkle features of the skin. Therefore, effective and accurate quantification of skin roughness is essential in skincare, medical treatment, and product development. This study proposes a method for estimating the skin surface roughness using optical coherence tomography (OCT) combined with a convolutional neural network (CNN). The proposed algorithm is validated through a roughness standard plate. Then, the experimental results revealed that skin surface roughness including arithmetic mean roughness and depth of roughness depends on age and gender. The advantage of the proposed method based on OCT is that it can reduce the effect of the skin surface’s natural curvature on roughness. In addition, the method is combined with the epidermal thickness and dermal attenuation coefficient for multi-parameter characterization of skin features. It could be seen as a potential tool for understanding the aging process and developing strategies to maintain and enhance skin health and appearance.

This paper is dedicated to the fundamental research of the mechanical model of a 1/4-vehicle semi-active suspension system with time-delayed state feedback control during wheel vertical displacement. The strategy combining the “equivalent harmonic excitation” optimization algorithm with the particle swarm optimization algorithm is proposed in this paper. Through the optimization and solution of time-delayed feedback control parameters of the 1/4 vehicle semi-active suspension system, the dynamic response of the vehicle suspension system before and after parameter optimization is studied. The research results indicate that, compared to passive control, time-delayed feedback control of wheel vertical displacement can significantly improve the smoothness, handling stability, and safety of vehicle operation.

The design for large-scale offshore systems like renewable energy systems as well as ship structures represents the key factor for the investigation and application of such devices. The existing guide for design schemes of offshore systems cannot cover novel large-scale design demand for recent offshore systems, as a result of the fast-growing scale of offshore systems but the late update of guides. To this end, this paper proposes a novel risk estimation approach of alternative design schemes for large-scale offshore systems as a basis to support the design scheme determinations. Initially, the risks of design schemes are analyzed by fault tree analysis. Subsequently, Bayesian networks and fuzzy sets are employed to calculate the reliability of alternative designs that comply with, or deviate from, the existing guides. The risk level of alternative designs is assessed to ensure the better performance of alternative design schemes in terms of safety. The Bayesian network approach proposed also accretions the weak links in the alternative designs. The results of this paper contribute to enhancing the survivability of offshore systems, such as renewable energy systems as well as ship structures.

Background: Non-compressible torso hemorrhage (NCTH) presents the ultimate challenge in pre-hospital care. While external hemorrhage control devices (EHCDs) such as the Abdominal Aortic and Junctional Tourniquet (AAJT) and SAM Junctional Tourniquet (SJT) have been invented, the current design and application strategy requires further improvement. Therefore, researchers devised a novel apparatus named Modified EHCD (M-EHCD) and implemented intermittent hemostasis (IH) as a preventive measure against ischemia-reperfusion injury. The objective of this study was to ascertain the combined effect of M-EHCD and IH on the hemostatic effect of NCTH. Methods: Eighteen swine were randomized to M-EHCD, AAJT or SJT. The NCTH model was established by inducing Class Ⅲ hemorrhagic shock and performing a hemi-transection of common femoral artery (CFA). EHCDs were rapidly fastened since the onset of free bleeding (T0min). The IH strategy was implemented by fully releasing M-EHCD at T40min, T70min and T100min, respectively, whereas AAJT and SJT maintained continuous hemostasis (CH) until T120min. All groups underwent CFA bridging at T110min, and EHCDs were removed at T120min. Reperfusion lasted for 60 min, after which euthanasia was performed. Hemodynamics, intra-vesical pressure (IVP), and blood samples were collected periodically. Histological examinations were also conducted. Results: M-EHCD demonstrated the fastest application time (M-EHCD: 26.38 ± 6.32s vs. SJT: 30.84 ± 5.62s vs. AAJT: 54.28 ± 5.45s, P

Pancreatic cancer (PC) is a highly malignant disease with high aggressiveness and a dismal prognosis, which is challenging to diagnose clinically early and gains low benefit from standard therapies. MicroRNAs (miRNAs) have become a hot topic in oncology research. Current evidence indicates that miRNAs are regulators involved in the entire process of PC, providing new diagnostic and therapeutic strategies for this fatal disease. Related research has been rapidly updated, making it necessary to review it to propose new directions and ideas and provide guidance for the development of precision medicine for PC. We reviewed the relevant literature through Pubmed, Embase, Web of Science and Medline, showing that abnormally expressed miRNAs in PC patients have the potential to be used as biomarkers for diagnosis and prognosis, highlighting the excellent prospect of combining miRNAs with traditional therapies, and the effective application of these factors for PC, especially miRNA mimics and inhibitors. MiRNAs participate in the entire process of PC and play important roles in diagnosis, treatment and prognosis. They are potential factors in conquering PC in the future.

In this paper, coal-based solid waste, including fly ash, desulfurization gypsum, furnace bottom slag, and coal washing sludge in the ratio of 3:2:3:2 with a total of 200 tons/0.07 hm2, were used as the specialized main material for restoring the saline alkali land of Emao River in Huairen of China. The remediation effect and safety of solid waste artificial soil were evaluated by testing the soil samples before and after the remediation. The results showed that the pH value of the soil after remediation decreased from 9.98 to 7.60, which was close to the neutral value and suitable for crop growth. The total amount of water-soluble salts decreased from 8.30 g kg−1 to 4.80 g kg−1 with a decrease of 42.2 %. The organic matter increased from 6.5 g kg−1 to 39.1 g kg−1 with a 5-fold increase. Compared to the original soil, the heavy metal content in the restored soil did not increased, but instead decreased, indicating that the restoration technology was feasible and meets environmental requirements. Corn planting experiment results showed that corn's emergence rate in the original saline alkali soil was extremely low (about 1 %), while in the restored soil reached over 99 %. The average yield of corn in restoration field was 16.56 % higher than the average local yield level. The residual content of heavy metals and organic toxic substances in corn and potatoes grown on restored soil were analyzed, and the results showed that the detected heavy metal content was far lower than the standard values, and the residual organic toxic substances were basically not detected, indicating that the agricultural fruits grown on restored soil were safe, harmless, and edible. This approach could achieve large-scale consumption of coal-based solid waste, increase arable land, and reduce the cost of restoring saline alkali land.

Abstract Background Pancreatoblastoma (PB) is one of the rare malignant tumors that typically occurs in children. Cases of PB in adults are highly unusual. This disease often presents with subtle symptoms and lacks characteristic clinical manifestations, leading to diagnostic challenges. Objective This study integrates the relevant literature on adult PB, conducting data analysis on clinical features, laboratory and imaging results, pathological characteristics, and treatments according to inclusion and exclusion criteria. Kaplan–Meier univariate analysis and Log‐rank tests are employed to analyze survival data from adult PB follow‐up, exploring factors influencing prognosis. Results A total of 65 articles were included, encompassing 103 cases of adult PB. The average age of PB patients was 41.78 years (range 19–81 years), and the male‐to‐female ratio was 1.06:1. Patients frequently presented with abdominal pain as the initial symptom. Laboratory results lacked specificity and imaging findings often presented as large, well‐defined masses. PB exhibited distinctive pathological features, including squamous corpuscles (n = 76, 89.41%) and acinar differentiation (n = 34, 40%), with frequent positive expression of Trypsin, Chymotrypsin, and AACT (Alpha‐1‐Antichymotrypsin). APC (Adenomatous Polyposis Coli) gene mutation was the most common molecular alteration in adult PB. During the follow‐up period, 43.59% of patients died (range 3 days to 348 months). The primary factors affecting prognosis were the presence of metastasis (χ2 = 3.996, p = 0.046) and incomplete surgical resection (χ2 = 5.586, p = 0.018), with mean survival times of 48 months and 27 months, respectively. Conclusions PB in adults is an invasive tumor. The key to distinguishing PB from other pancreatic tumors lies in recognizing its unique pathological feature, the squamous corpuscles. Timely and complete surgical resection is the preferred treatment following diagnosis. Patients with incomplete resection or the presence of lymph nodes or (and) distant metastases have a poor prognosis.

BackgroundMultiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by increased inflammation and immune responses, oxidative injury, mitochondrial dysfunction, and iron dyshomeostasis leading to demyelination and axonal damage. In MS, incomplete remyelination results in chronically demyelinated axons and degeneration coinciding with disability. This suggests a failure in the ability to remyelinate in MS, however, the precise underlying mechanisms remain unclear. We aimed to identify proteins whose expression was altered in chronic inactive white matter lesions and periplaque white matter in MS tissue to reveal potential pathophysiological mechanisms.MethodsLaser capture microdissection coupled to proteomics was used to interrogate spatially altered changes in formalin-fixed paraffin-embedded brain tissue from three chronic MS individuals and three controls with no apparent neurological complications. Histopathological maps guided the capture of inactive lesions, periplaque white matter, and cortex from chronic MS individuals along with corresponding white matter and cortex from control tissue. Label free quantitation by liquid chromatography tandem mass spectrometry was used to discover differentially expressed proteins between the various brain regions.ResultsIn addition to confirming loss of several myelin-associated proteins known to be affected in MS, proteomics analysis of chronic inactive MS lesions revealed alterations in myelin assembly, metabolism, and cytoskeletal organization. The top altered proteins in MS inactive lesions compared to control white matter consisted of PPP1R14A, ERMN, SIRT2, CARNS1, and MBLAC2.ConclusionOur findings highlight proteome changes in chronic inactive MS white matter lesions and periplaque white matter, which may be crucial for proper myelinogenesis, bioenergetics, focal adhesions, and cellular function. This study highlights the importance and feasibility of spatial approaches such as laser capture microdissection-based proteomics analysis of pathologically distinct regions of MS brain tissue. Identification of spatially resolved changes in the proteome of MS brain tissue should aid in the understanding of pathophysiological mechanisms and the development of novel therapies.

Abstract Background Long-term exposure to a high altitude environment with low pressure and low oxygen could cause abnormalities in the structure and function of the heart. Myocardial strain is a sensitive indicator for assessing myocardial dysfunction, monitoring myocardial strain is of great significance for the early diagnosis and treatment of high altitude heart-related diseases. This study applies cardiac magnetic resonance tissue tracking technology (CMR-TT) to evaluate the changes in left ventricular myocardial function and structure in rats in high altitude environment. Methods 6-week-old male rats were randomized into plateau hypoxia rats (plateau group, n = 21) as the experimental group and plain rats (plain group, n = 10) as the control group. plateau group rats were transported from Chengdu (altitude: 360 m), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (altitude: 3850 m), Yushu, China, and then fed for 12 weeks there, while plain group rats were fed in Chengdu(altitude: 360 m), China. Using 7.0 T cardiac magnetic resonance (CMR) to evaluate the left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), as well as myocardial strain parameters including the peak global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). The rats were euthanized and a myocardial biopsy was obtained after the magnetic resonance imaging scan. Results The plateau rats showed more lower left ventricular GLS and GRS (P 0.05). Conclusions After 12 weeks of exposure to high altitude low-pressure hypoxia environment, the left ventricular global strain was partially decreased and myocardium is damaged, while the whole heart ejection fraction was still preserved, the myocardial strain was more sensitive than the ejection fraction in monitoring cardiac function.

Abstract Background Deubiquitinating enzymes (DUBs) cleave ubiquitin on substrate molecules to maintain protein stability. DUBs reportedly participate in the tumorigenesis and tumour progression of hepatocellular carcinoma (HCC). OTU deubiquitinase 5 (OTUD5), a DUB family member, has been recognized as a critical regulator in bladder cancer, breast cancer and HCC. However, the expression and biological function of OTUD5 in HCC are still controversial. Results We determined that the expression of OTUD5 was significantly upregulated in HCC tissues. High levels of OTUD5 were also detected in most HCC cell lines. TCGA data analysis demonstrated that high OTUD5 expression indicated poorer overall survival in HCC patients. OTUD5 silencing prominently suppressed HCC cell proliferation, while its overexpression markedly enhanced the proliferation of HCC cells. Mass spectrometry analysis revealed solute carrier family 38 member 1 (SLC38A1) as a candidate downstream target protein of OTUD5. Coimmunoprecipitation analysis confirmed the interaction between OTUD5 and SLC38A1. OTUD5 knockdown reduced and OTUD5 overexpression increased SLC38A1 protein levels in HCC cells. However, OTUD5 alteration had no effect on SLC38A1 mRNA expression. OTUD5 maintained SLC38A1 stability by preventing its ubiquitin-mediated proteasomal degradation. SLC38A1 silencing prominently attenuated the OTUD5-induced increase in HCC cell proliferation. Finally, OTUD5 knockdown markedly suppressed the growth of HCC cells in vivo. Conclusions OTUD5 is an oncogene in HCC. OTUD5 contributes to HCC cell proliferation by deubiquitinating and stabilizing SLC38A1. These results may provide a theoretical basis for the development of new anti-HCC drugs.

Abstract Average windward area is an important index for calculating the trajectory, velocity attenuation and terminal effect of explosive fragments. In order to solve the problems that existing theoretical method cannot calculate windward area of irregular fragment and experiment method is not convenient for automatic calculation and has low accuracy, a Monte Carlo subdivision projection simulation algorithm is proposed. The average windward area of arbitrary shaped fragments can be obtained with coordinate translation, random rotation, plane projection, convex-hull triangulation, concave boundary searching and sorting with maximum edge length constraint, subdivision area calculation, and averaging by thousands of cycles. Results show that projection area obtained by the subdivision projection algorithm is basically the same as that obtained by software method of computer aided design. Moreover, the maximum calculation error of the algorithm is less than 7%, and its accuracy is much higher than that of the equivalent ellipsoid method. The average windward area calculated by the Monte Carlo subdivision projection simulation algorithm is consistent with theoretical formula for prefabricated fragments, and the error is less than 3%. The convergence and accuracy of the Monte Carlo subdivision projection algorithm are better than those of the icosahedral uniform orientation method.

Abstract Hard carbons are emerging as the most viable anodes to support the commercialization of sodium-ion (Na-ion) batteries due to their competitive performance. However, the hard carbon anode suffers from low initial Coulombic efficiency (ICE), and the ambiguous Na-ion (Na+) storage mechanism and interfacial chemistry fail to give a reasonable interpretation. Here, we have identified the time-dependent ion pre-desolvation on the nanopore of hard carbons, which significantly affects the Na+ storage efficiency by altering the solvation structure of electrolytes. Consummating the pre-desolvation by extending the aging time, generates a highly aggregated electrolyte configuration inside the nanopore, resulting in negligible reductive decomposition of electrolytes. When applying the above insights, the hard carbon anodes achieve a high average ICE of 98.21% in the absence of any Na supplementation techniques. Therefore, the negative-to-positive capacity ratio can be reduced to 1.02 for full cells, which enables an improved energy density. The insight into hard carbons and related interphases may be extended to other battery systems and support the continued development of battery technology.

Abstract Recent studies have reported the involvement of peripheral nervous system (PNS) in association with MOG‐IgG, including isolated neuropathies. In this retrospective study we characterized the PNS involvement in MOG antibody associated disease (MOGAD). Six out of 215 MOGAD patients had PNS involvement (all polyradiculopathy) that occurred concurrently with a CNS demyelinating episode. We also demonstrated MOG expression in healthy human controls' proximal nerve root. Nine patients with true‐positive MOG‐IgG1 had PNS involvement temporally unrelated to a CNS demyelinating event. All these patients had an alternate etiology of PNS involvement. Isolated peripheral neuropathy is not a feature of MOGAD, but inflammatory nerve root involvement can occur concurrently with CNS demyelinating events.

Abstract Human factors and plant characteristics are important drivers of plant invasions, which threaten ecosystem integrity, biodiversity and human well-being. However, while previous studies often examined a limited number of factors or focused on a specific invasion stage (e.g., naturalization) for specific regions, a multi-factor and multi-stage analysis at the global scale is lacking. Here, we employ a multi-level framework to investigate the interplay between plant characteristics (genome size, Grime’s adaptive CSR-strategies and native range size) and economic use and how these factors collectively affect plant naturalization and invasion success worldwide. While our findings derived from structural equation models highlight the substantial contribution of human assistance in both the naturalization and spread of invasive plants, we also uncovered the pivotal role of species’ adaptive strategies among the factors studied, and the significantly varying influence of these factors across invasion stages. We further revealed that the effects of genome size on plant invasions were partially mediated by species adaptive strategies and native range size. Our study provides insights into the complex and dynamic process of plant invasions and identifies its key drivers worldwide.

Abstract Demethoxylation was kinetically and spectroscopically studied over three catalysts with different Ru0/Ruδ+ ratios. In-situ spectroscopic tests demonstrated that the synergy between Ru0 and Ruδ+ was crucial, and Ru0 was in charge of H2 activation and adsorption of aromatic ring while Ruδ+ adsorbed with O in methoxyl. A Langmuir–Hinshelwood kinetic model was proposed, and ratio of Ru0/Ruδ+ was the key in deciding the rate-determining step (RDS): i) desorption of toluene was RDS over catalyst with high Ru0 ratio; ii) dissociation of H2 was RDS over Ruδ+ enriched catalyst; iii) demethoxylation was rate-determined by CO water–gas shift (WGS) when Ru0/Ruδ+ approached ~ 1. The best performance was obtained over Ru/NiAl2O4-200, which effectively enabled both C-O bond activation and rapid recovery of adsorption sites for aromatic rings. Finally, in-situ DRIFT studies on methoxy decomposition and CO-WGS unraveled that the electronic composition of Ru was more stable in Ru/NiAl2O4-200 which contributes to its excellence.

ObjectiveTo explore the efficacy and safety of nafamostat mesylate (NM) in patients on continuous renal replacement therapy (CRRT) at a high risk of hemorrhage.MethodsFrom March 2021 to February 2022, a retrospective study was conducted for 61 CRRT patients at a high risk of hemorrhage in intensive care unit of Shanghai Changhai Hospital. They were assigned into two groups of NM anticoagulation (n=33) and no anticoagulation (n=28). The effectiveness, safety and economy of anticoagulation were assessed.ResultsBaseline profiles differed insignificantly between two groups. No obvious adverse reactions occurred during treatment. The anticoagulant effective rate of NM anticoagulation group was significantly higher than that of no anticoagulant group (93.9% vs 28.6%, P0.05]. The elevation of venous pressure was significantly higher in heparin free anticoagulant group than that in NM group (P=0.001) and the level of transmembrane pressure was also higher than that in NM group at the end of treatment (P=0.003). No significant change occurred in hemoglobin level before versus after CRRT in NM group (P>0.05).ConclusionNM is a safe and effective anticoagulant for CRRT patients at a high risk of hemorrhage and allows sufficient filter survival without a higher risk of hemorrhage.

Alien species are colonizing mountain ecosystems and increasing their elevation ranges in response to ongoing climate change and anthropogenic disturbances, posing increasing threats to native species. However, how quickly alien species spread upward and what drives their invasion remains insufficiently understood. Here, using 26,952 occurrence records of 58 alien plant species collected over two centuries in the Czech Republic, we explored the elevation range and invasion speed of each alien species and the underlying factors driving these variables. We collected species traits relevant for invasion (e.g., clonality, flowering time, life span, invasion status, height, mycorrhizal type, native range, naturalized range, monoploid genome size, and Ellenberg-type indicator values for light, temperature, and nitrogen), human-associated factors (e.g., introduction pathways and the sum of economic use types), and minimum residence time. We explored the relationships between these factors and species’ elevation range and invasion speed using phylogenetic regressions. Our results showed that 58 alien species have been expanding upward along mountain elevations in the Czech Republic over the past two centuries. A stronger effect of species’ traits than human-associated factors has been revealed, e.g., clonality was a key trait supporting the invasion of alien species into the mountains, while human-associated factors showed no effect. Our findings highlight that the characteristics associated with rapid reproduction and spread are crucial for alien species’ invasion into montane regions. Identifying key drivers of this process is important for predicting the spatiotemporal dynamics of alien species in high-altitude ecosystems and thus employing apposite measures to reduce the threat to native plant species.

Hydrogels have a unique three-dimensional network that can create a good environment for the loading of functional compounds; hence, they have considerable potential in the delivery of bioactive substances. Natural macromolecular substances (proteins, polysaccharides) have the features of low toxicity, degradability, and biosafety; thus, they can be employed in the manufacture of hydrogels in the food sector. With its customizable viscoelastic and porous structure, hydrogels are believed to be good bioactive material delivery vehicles, which can effectively load polyphenols, vitamins, probiotics, and other active substances to prevent their influence from the external environment, thereby improving its stability. In this research, the common raw materials, preparation methods, and applications in the delivery of bioactive elements of food gels were examined; this study aimed at presenting new ideas for the development and utilization of protein-based food gels.