Search

Abstract Extracellular adenosine is extensively involved in regulating the tumor microenvironment. Given the disappointing results of adenosine-targeted therapy trials, personalized treatment might be necessary, tailored to the microenvironment status of individual patients. Here, we introduce the adenosine signaling score (ADO-score) model using non-negative matrix fraction identified patient subtypes using publicly available melanoma dataset, which aimed to profile adenosine signaling-related genes and construct a model to predict prognosis. We analyzed 580 malignant melanoma samples and demonstrated its robust value for prognosis. Further investigation in immune checkpoint inhibitor dataset suggests its potential as a stratified factor of immune checkpoint inhibitor efficacy. We validated the power of the ADO-score at the protein level immunofluorescence in a melanoma cohort from Xiangya Hospital. More importantly, single-cell and spatial transcriptomic data highlighted the cell-specific expression patterns of adenosine signaling-related genes and the existence of adenosine signaling-mediated crosstalk between tumor cells and immune cells in melanoma. Our study reveals a robust connection between adenosine signaling and clinical benefits in melanoma patients and proposes a universally applicable adenosine signaling model, the ADO-score, in gene expression profiles and histological sections. This model enables us to more precisely and conveniently select patients who are likely to benefit from immunotherapy.

Casing stress distribution is one of the most relevant topics in the study of the wellbore stress field. Due to factors such as uneven geostress, the wellbore is often elliptical, and the casing may not necessarily be in the center of the wellbore. This article adopts the theory of elasticity and uses the finite element method for calculation. The main research focuses on the effects of ovality and eccentricity on the overall stress distribution of the casing and the stress distribution at the interface between the casing and cement sheath (i.e., the outer wall of the casing). The research results indicated that when the casing is centered, higher ellipticity is beneficial for improving the casing’s response to non-uniform stress. However, when the casing is eccentric, higher ellipticity significantly increases the non-uniformity of the stress distribution and the risk of stress concentration in the casing. The risk of casing failure increases with increasing non-uniform stress. Additionally, a lower elastic modulus and higher Poisson ratio of the cement can improve the casing’s response to stress. This research result has a certain reference value for implementing high-quality cementing construction and ensuring the normal production of oil and gas wells.

The fatigue crack growth properties of G20Mn5QT cast steel and corresponding butt welds, using compact tension specimens, were monitored and investigated via acoustic emission (AE) techniques. Fatigue crack growth is a combination of cyclic plastic deformations before the crack tip, tensile crack fractures, and shear crack fractures. The cyclic plastic deformations release the maximum amount of energy, which accounts for half of the total energy, and the second-largest number of AE signals, which are of the continuous-wave type. The tensile crack fractures release the second-largest amount of energy and the largest number of AE signals, which are of the burst-wave type. The shear crack fractures release the least amount of energy and the lowest number of AE signals, which are similar to the burst type, albeit with a relatively longer rise time and duration. Crack tip advancement can be regarded as a discontinuous process. The critical area before the crack tip brittlely ruptures when the fatigue damage caused by cyclic plastic deformations reaches critical status. The ruptures produce a large number of tensile crack fractures and rare shear crack fractures. Through fractography observation, the shear crack fractures occur probabilistically around defects caused by casting or welding, which lead to stress and strain in the local complex.

Abstract Keloids are benign fibroproliferative tumors that severely diminish the quality of life due to discomfort, dysfunction, and disfigurement. Recently, ultrasound technology as a noninvasive adjuvant therapy is developed to optimize treatment protocols. However, the biophysical mechanisms have not yet been fully elucidated. Here, it is proposed that piezo‐type mechanosensitive ion channel component 1 (Piezo1) plays an important role in low‐frequency sonophoresis (LFS) induced mechanical transduction pathways that trigger downstream cellular signaling processes. It is demonstrated that patient‐derived primary keloid fibroblasts (PKF), NIH 3T3, and HFF‐1 cell migration are inhibited, and PKF apoptosis is significantly increased by LFS stimulation. And the effects of LFS is diminished by the application of GsMTx‐4, the selective inhibitor of Piezo1, and the knockdown of Piezo1. More importantly, the effects of LFS can be imitated by Yoda1, an agonist of Piezo1 channels. Establishing a patient‐derived xenograft keloid implantation mouse model further verified these results, as LFS significantly decreased the volume and weight of the keloids. Moreover, blocking the Piezo1 channel impaired the effectiveness of LFS treatment. These results suggest that LFS inhibits the malignant characteristics of keloids by activating the Piezo1 channel, thus providing a theoretical basis for improving the clinical treatment of keloids.

BackgroundTransient receptor potential vanilloid (TRPV) is one of the transient receptor potential protein groups; cardiovascular system disease is a crucial cause of mortality among people globally.ObjectiveThis article is intended to accomplish a bibliometric analysis of the trends and public interest since TRPV was reported for the first time.MethodsThe article summarized the Web of Science (WOS) Core Collection on the relationship between TRPV and cardiovascular system disease each year from 2000 to 2021. Data extraction and visualization were completed by R package bibliometrix. Keyword citation burst and co-citation networks were generated and produced by CiteSpace. The map evaluating the distribution of country and region was painted in GunnMap 2 (lert.co.nz). The ranking was performed using the Standard Competition Ranking method. Co-authorship and co-occurrence were analyzed with VOSviewer.ResultsAfter removing duplicated data, books, conference proceedings, and articles of uncertain age, 493 were included, and 17 were excluded. The pattern of publication years showed that the number of publications increased rapidly from 2008 to 2021 with no peak in the number of publications until 2021. The geographical distribution pattern revealed a considerable gap in the number of publications between the United States, China, and other countries, with East Asian institutions leading the world in this area. The pattern of co-authorship showed that 77 institutions were divided into 19 clusters, each covering one country or region.These results suggest that intercontinental cooperation among institutions should be strengthened. The core authors section displayed the change in the most published authors. Keyword analysis listed six burst keywords. Co-citation analysis of references from 2011 to 2021 showed the number and centrality of citations to leading articles.ConclusionOur findings reveal trends and public interest in transient receptor potential vanilloid for cardiovascular disease. These findings suggest that the field has experienced significant growth since 2008, with the United States and China in dominant positions. Our findings also suggest that intercontinental cooperation should be strengthened, and that future research hotspots may focus on pharmacological mechanisms and in-depth exploration of drug clinical trials and new clinical disease application areas such as hypertension, diabetes, and cardiac arrhythmias, which could serve as a foundation for further research.

BackgroundMelanoma is one of the most life-threatening skin cancers; immune checkpoint blockade is widely used in the treatment of melanoma because of its remarkable efficacy. ObjectiveThis study aimed to conduct a comprehensive bibliometric analysis of research conducted in recent decades on immune checkpoint blockade for melanoma, while exploring research trends and public interest in this topic. MethodsWe summarized the articles in the Web of Science Core Collection on immune checkpoint blockade for melanoma in each year from 1999 to 2020. The R package bibliometrix was used for data extraction and visualization of the distribution of publication year and the top 10 core authors. Keyword citation burst analysis and cocitation networks were calculated with CiteSpace. A Gunn online world map was used to evaluate distribution by country and region. Ranking was performed using the Standard Competition Ranking method. Coauthorship analysis and co-occurrence were analyzed and visualized with VOSviewer. ResultsAfter removing duplicates, a total of 9169 publications were included. The distribution of publications by year showed that the number of publications rose sharply from 2015 onwards and either reached a peak in 2020 or has yet to reach a peak. The geographical distribution indicated that there was a large gap between the number of publications in the United States and other countries. The coauthorship analysis showed that the 149 top institutions were grouped into 8 clusters, each covering approximately a single country, suggesting that international cooperation among institutions should be strengthened. The core author extraction revealed changes in the most prolific authors. The keyword analysis revealed clustering and top citation bursts. The cocitation analysis of references from 2010 to 2020 revealed the number of citations and the centrality of the top articles. ConclusionsThis study revealed trends in research and public interest in immune checkpoint blockade for melanoma. Our findings suggest that the field is growing rapidly, has several core authors, and that the United States is taking the lead position. Moreover, cooperation between countries should be strengthened, and future research hot spots might focus on deeper exploration of drug mechanisms, prediction of treatment efficacy, prediction of adverse events, and new modes of administration, such as combination therapy, which may pave the way for further research.

BackgroundMacrolides have been widely used to treat moderate-to-severe acne for more than 50 years. However, the prevalent antibiotic resistance of Propionibacterium acnes, along with the absence of clinically available resistance tests, has made macrolide misuse a frequent occurrence around the globe, with serious consequences.ObjectiveWe developed Cutibacterium acnes quantitative PCR (qPCR)-based antibiotics resistance assay (ACQUIRE) to enable fast and accurate detection of C. acnes macrolide resistance in clinical settings, representing an opportunity to administer antibiotics more wisely and improve the quality of care.MethodsA cross-sectional observational study (n = 915) was conducted to probe into the macrolide resistance of C. acnes in patients with acne.ResultsThe high sensitivity of ACQUIRE enabled us to reveal a much higher C. acnes 23S recombinant DNA (rDNA) point mutation rate (52%) and thus a higher macrolide resistance (75.5%) compared to previous reports. Carriage of ermX gene was discovered on 472 (53%) subjects, which concurs with previous studies.ConclusionThe macrolide resistance of C. acnes is much higher than previously reported. Integrating ACQUIRE into acne treatment modalities may eliminate macrolide misuse and achieve better clinical improvements.

Ligand-free BaF2:Nd nanoparticles (NPs) with a size of 10 nm were fabricated by a novel synthetic route in the liquid phase. A transparent dispersion of the BaF2:Nd NPs mixed with propanetriol and DMSO-d6 was done. Highly stable and outstanding near-infrared (NIR) fluorescence centered at 1,058 nm was detected using an excitation wavelength of 808 nm laser. Moreover, the dispersion can be found to be stable for over 1 month, and the cytotoxicity of the BaF2:Nd NP dispersion has also been studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The superior performance of these NPs exhibits their great potential application in high-contrast and high-penetration in vivo imaging.

Cymbidium iridioides D. Don 1852 is a Class I endangered species in China having important ornamental and breeding values. This study used Illumina high-throughput sequencing technology to sequence the complete chloroplast genome of C. iridioides. The genome features of C. iridioides and its phylogenetic relationships were determined. The complete chloroplast genome is 156,599 bp, containing a pair of 26,736 bp inverse duplication regions, a large 85,242 bp single-copy region, and a small 17,885 bp single-copy region. The entire genome contains 76 protein-coding genes, 37 tRNA genes, and 4 rRNA genes. A phylogenetic tree of 25 Orchidaceae species revealed that C. iridioides was grouped within Sect. Iridorchis and comprised a clade with Cymbidium tracyanum.

Since the 1950s, gradual changes in the gut microbiota of patients with hepatic encephalopathy have been observed. Previous research has indicated potential associations between the gut and brain, and the gut microbiota is becoming a hot topic in research on diseases of the nervous system. However, for the past few decades, studies of hepatic encephalopathy have been restricted to controlling the gut microbiota during macroscopic manipulation, such as probiotic intervention, while its clinical use remains controversial, and the cellular mechanisms underlying this condition are still poorly understood. This thesis seeks to comprehensively understand and explain the role of gut microbiota in hepatic encephalopathy as well as analyze the effects of intervention by regulating the gut microbiota. Evidence is presented that shows that dysbiosis of the gut microbiota is the primary pathological driver of hepatic encephalopathy and impacts pathologic progression via complex regulatory networks. As a result, suggestions were identified for future mechanistic research and improvements in therapeutic strategies for hepatic encephalopathy.

Due to the limited space of offshore platform, it is unable to implement large-scale multistage hydraulic fracturing for the horizontal well in Lufeng offshore oilfield. Thus, multistage hydraulic fracturing technology in directional well was researched essentially to solve this problem. Modeling of fracture propagation during multistage fracturing in the directional and horizontal wells in artificial cores was carried out based on a true triaxial hydraulic fracturing simulation experiment system. The effects of horizontal stress difference, stage spacing, perforation depth, and well deviation angle on multifracture propagation were investigated in detail. Through the comparative analysis of the characteristics of postfrac rock and pressure curves, the following conclusions were obtained: (1) multistage fracturing in horizontal wells is conducive to create multiple transverse fractures. Under relatively high horizontal stress difference coefficient (1.0) and small stage spacing conditions, fractures tend to deflect and merge due to the strong stress interference among multiple stages. As a consequence, the initiation pressure for the subsequent stages increases by more than 8%, whereas in large stage spacing conditions, the interference is relatively lower, resulting in the relatively straight fractures. (2) Deepening perforation holes can reduce the initiation pressure and reduce the stress interference among stages. (3) When the projection trace of directional wellbore on horizontal plane is consistent with the direction of the minimum horizontal principal stress, fractures intersecting the wellbore obliquely are easily formed by multistage fracturing. With the decrease of well deviation angle, the angle between fracture surface and wellbore axis decreases, which is not conducive to the uniform distribution of multiple fractures. (4) When there is a certain angle between the projection trace of directional wellbore on horizontal plane and the direction of minimum horizontal principal stress, the growth of multiple fractures is extremely ununiform and the fracture paths are obviously tortuous.

We theoretically investigate a Dy3+-doped chalcogenide fiber lasers operating at 4.3 μ m based on the rate equations and propagation equations. The two main pump bands for 1319 and 1707 nm corresponding to the 6H15/2→6H9/2 and 6H15/2→6H13/2 transitions are discussed in detail. The predicted maximum slope efficiencies are determined to be ~7.8% and ~15.1% for the two pumping wavelength, respectively. Besides, the variety of laser performance has been systematically analyzed when the pump configurations, fiber length, fiber loss are varied. This numerical analysis might be useful to explore the 4.3 μm lasing operation for the mid-infrared chalcogenide fiber lasers in future.

Secondary electron emission (SEE) plays a crucial role in the gain performance of devices, such as electron multipliers and microchannel plates (MCPs). Gain performance could be improved by increasing the secondary electron yield (SEY) of device surface. Al2O3 coating is an ideal material for SEE, benefiting from its high SEY. The Al2O3 coating deposited on inner device walls by atomic layer deposition (ALD) can improve the gain performance of devices. In this study, the SEE characteristics of Al2O3 coatings were investigated experimentally. A series of Al2O3 coatings with thicknesses of 1-30 nm were prepared on Si substrate through the ALD method. Then, the SEY of the coatings were quantified as a function of primary electron energy in the range of 100∼1500 eV. Furthermore, an equation describing the true SEY as a function of thickness was established by applying theory of Dionne’s SEE model. This work presents potential approach for controlling the SEE level of Al2O3 coatings through thickness adjustment and is crucial for comprehending the SEE of composite materials.

In this study, bromelain was used to break soy protein molecules into polypeptide chains, and triglycidylamine (TGA) was added to develop a bio-adhesive. The viscosity, residual rate, functional groups, thermal behavior, and fracture surface of different adhesives were measured. A three-ply plywood was fabricated and evaluated. The results showed that using 0.1 wt% bromelain improved the soy protein isolate (SPI) content of the adhesive from 12 wt% to 18 wt%, with viscosity remaining constant, but reduced the residual rate by 9.6% and the wet shear strength of the resultant plywood by 69.8%. After the addition of 9 wt% TGA, the residual rate of the SPI/bromelain/TGA adhesive improved by 13.7%, and the wet shear strength of the resultant plywood increased by 681.3% relative to that of the SPI/bromelain adhesive. The wet shear strength was 30.2% higher than that of the SPI/TGA adhesive, which was attributed to the breakage of protein molecules into polypeptide chains. This occurrence led to (1) the formation of more interlocks with the wood surface during the curing process of the adhesive and (2) the exposure and reaction of more hydrophilic groups with TGA to produce a denser cross-linked network in the adhesive. This denser network exhibited enhanced thermal stability and created a ductile fracture surface after the enzymatic hydrolysis process.

During oil and gas extraction, alternating wellbore pressures can induce cyclic loading, which can potentially lead to structural damage of the casing cement sheath, posing safety risks. An analytical model for the elastic deformation stage of the cement sheath was developed to investigate its mechanical response and failure modes during well operations. A casing-cement sheath-formation system model and thick-walled cylinder theory were utilized. Analytical expressions for the elastic deformation stage were derived. These expressions were validated through finite element analysis. Results show that, the cement sheath primarily fails in either tensile or compressive modes. As the elastic modulus increases, a transition from compressive to tensile failure modes occurs. When the elastic modulus exceeds 40 GPa, the effect on radial stress stabilizes. Moreover, when the casing pressure reaches 60 MPa, the cement sheath expands outward, transitioning from a compressive state to a tensile state in the circumferential direction. This study provides valuable insights for analysing mechanical response parameters and evaluating the safety of the casing cement sheath during operations. [ABSTRACT FROM AUTHOR]

The rice water weevil, Lissorhoptrus oryzophilus Kuschel (Coleoptera: Curculionidae), threatens global rice production, with invasion events driven by its parthenogenetic populations. However, the global establishment risk in global rice-growing areas and potential economic losses and control benefits of the populations in invaded areas remain unclear. We applied an optimized MaxEnt model to predict the global suitable areas of the populations under current and future climate scenarios. Furthermore, we used @Risk software to estimate the potential economic losses and controlling benefit of this populations to rice production in China. Compared to its native range (North America), this populations has explored novel climates ecological niches in invaded areas (Europe and Asia) and occupies the broadest range of climatic ecological niches in Asia. The highly suitable area is primarily covered in rice-growing areas in China, the Korean Peninsula, and Japan, with all major rice-growing areas concentrated in these countries and regions. Under SSP1-2.6 and SSP5-8.5 emission scenarios, sum of suitable area for the populations in global rice-growing regions is projected to decrease by 0.35% and 0.26%, respectively, by the 2030s and 2050s. Moreover, @Risk analysis indicates that without control measures, the populations could cost China’s rice industry $18.95 billion, but management efforts could recover $17.54 billion. These results provide in-depth reference about the impact of climatic changes on the potential global suitable range of L. oryzophilus parthenogenetic populations and its economic impact on the rice industry in China.

Epiphyas postvittana, commonly known as the light brown apple moth (LBAM), is native to Australia and has a restricted global distribution. Its polyphagous nature and the recent surge in interceptions have emphasized the need for focused risk assessments to guide effective measures to curb the entry of this pest into new countries. This study aimed to perform a detailed global invasion risk assessment using an optimized MaxEnt model that incorporated 19 bioclimatic variables and elevation. The predictive outcomes underscored the significance of key variables, specifically the minimum temperature of the coldest month (bio6), precipitation of the driest month (bio14), and precipitation of the coldest quarter (bio19), in shaping the potential geographical distribution of LBAM. Regions beyond the existing range, including the southeastern United States, southern Brazil, eastern Argentina, Uruguay, southern Chile, and various Western European countries, were identified as susceptible to invasion and establishment by LBAM. An increase in suitability was observed above 45°N and 40°S under future climate scenario. With respect to climate change, LBAM would expand its potential range in Western Europe and the United States, especially under SSP5-8.5, in the 2050s. An upward trend in the latitudinal suitability gradient for LBAM in mid-high latitude areas implies that amid changing climate conditions, LBAM may find favorable habitats in these regions. For countries and regions with invasion risk, it is imperative to implement corresponding inspections and quarantine measures to thwart the introduction of LBAM, particularly in countries with established trade ties with invaded regions.