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Abstract Osteoarthritis (OA) is the most common form of arthritic disease, and phenotypic modification of chondrocytes is an important mechanism that contributes to the loss of cartilage homeostasis. This study identified that Fascin actin-bundling protein 1 (FSCN1) plays a pivotal role in regulating chondrocytes phenotype and maintaining cartilage homeostasis. Proteome-wide screening revealed markedly upregulated FSCN1 protein expression in human OA cartilage. FSCN1 accumulation was confirmed in the superficial layer of OA cartilage from humans and mice, primarily in dedifferentiated-like chondrocytes, associated with enhanced actin stress fiber formation and upregulated type I and III collagens. FSCN1-inducible knockout mice exhibited delayed cartilage degeneration following experimental OA surgery. Mechanistically, FSCN1 promoted actin polymerization and disrupted the inhibition of Decorin on TGF-β1, leading to excessive TGF-β1 production and ALK1/Smad1/5 signaling activation, thus, accelerated chondrocyte dedifferentiation. Intra-articular injection of FSCN1-overexpressing adeno-associated virus exacerbated OA progression in mice, which was mitigated by an ALK1 inhibitor. Moreover, FSCN1 inhibitor NP-G2-044 effectively reduced extracellular matrix degradation in OA mice, cultured human OA chondrocytes, and cartilage explants by suppressing ALK1/Smad1/5 signaling. These findings suggest that targeting FSCN1 represents a promising therapeutic approach for OA.

Uranium is the main fuel of nuclear power, and the removal of uranium from uranium-containing wastewater is important for environmental protection and resource recovery. Photo-induced uranyl ion removing is an economical and efficient method to remove U(Ⅵ) from uranium-containing wastewater. Many materials have been used for photo-induced reduction of U(Ⅵ). However, the practical application of most materials is still limited by many factors, such as the complexity of its synthesis process, the harsh conditions required, and the poor selectivity and reusability in the photocatalytic process. More importantly, most materials can only be photocatalyzed under the protection of an inert atmosphere. In the presence of oxygen, the photocatalytic product uranium dioxide(UO2) is unstable and easily oxidized resulting in reduced removal effect, so it becomes particularly vital to find an effective catalyst. Carbon dots(CDs) are a new type of carbon-based materials with excellent fluorescence performance, good water solubility and biocompatibility. However, due to the small size and hydrophilicity of the CDs, it is difficult to separate from water. It needs to be combined with other solid materials when applied. The application of CDs to the photocatalytic removal of uranyl ions in water has rarely been studied. Silica(SiO2) is an ideal loader due to its excellent mechanical strength and irradiation stability, as well as its large specific surface area and easy modification. In this paper, a blue carbon dot was prepared by solvothermal method and CDs/SiO2 composites were synthesized by sol-gel method. The morphology of the composite was characterized by scanning electron microscopy(SEM) and transmission electron microscopy(TEM) technologies, and their application in photocatalytic removal of uranium were studied. Under visible light irradiation, CDs/SiO2-b can remove more than 95% of uranium in 100 min. Experiments have found that the photo-precipitation rate of silica to uranium after the introduction of carbon dots is about 5.8 times of that of the pure silica, and uranium can be transformed into solid product of (UO2)O2•2H2O under air atmosphere, with a removal capacity of more than 800 mg/g. The morphology and structure of the photocatalytic products were characterized by SEM and XPS technology, and the solid products were easy to separate and remove. In order to evaluate the practical application of CDs/SiO2 light-induced reduction of uranium under visible light irradiation, pH and other influencing factors were systematically studied. Moreover, the removal efficiency of uranium is higher 85% after 5 cycles of recycling, showing excellent recycling performance. CDs/SiO2 composites are simple to prepare and can efficiently remove uranyl ions in water through photoinduction, which provides a new method and material for photoinduced removal of uranium.

Abstract The environmental impact of traded plastic waste hinges on how it is treated. Existing studies often use domestic or scenario-based recycling rates for imported plastic waste, which is problematic due to differences in recyclability and the fact that importers pay for it. We estimate the minimum required recycling rate (RRR) needed to break even financially by analysing import prices, recycling costs, and the value of recycled plastics across 22 leading importing countries and four plastic waste types during 2013–2022. Here we show that at least 63% of imported plastic waste must be recycled, surpassing the average domestic recycling rate of 23% by 40 percentage points. This discrepancy suggests that recycled plastics volumes from the global North-to-South trade may be underestimated. The country-specific RRR provided could enhance research and policy efforts to better quantify and mitigate the environmental impact of plastic waste trade.

Abstract Purpose To investigate the repeatability and reproducibility of a new method for centration analysis after small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK (FS-LASIK). Methods This study comprised 29 eyes treated with SMILE and 24 with FS-LASIK. Decentrations were analyzed using tangential and pachymetry difference maps respectively. Both difference maps were generated with a Scheimpflug tomographer (Pentacam) for each eye, using preoperative and 3-month postoperative scans. Repeatability and reproducibility were evaluated by calculating the intraclass correlation coefficient (ICC), within-subject standard deviation (Sw), and coefficient of repeatability (CR). Results ICC, Sw, and CR showed good to excellent repeatability in locating the coordinates of the optical zone (OZ) center on both maps, with values ranging from 0.84 to 0.96, 0.03 to 0.13, and 0.08 to 0.36 respectively. The repeatability of the total decentration from the preoperative corneal vertex on the tangential curvature difference maps( $$d_{TC}$$ d TC ) and the pachymetry difference maps( $$d_{PC}$$ d PC ) were moderate and good, respectively. The ICC, Sw, and CR of $$d_{TC}$$ d TC were 0.63, 0.09, and 0.25, respectively. The ICC, Sw, and CR of $$d_{PC}$$ d PC were 0.77, 0.10, and 0.28, respectively. The reproducibility of the OZ center measurements was excellent for the tangential difference maps (ICC $$\ge 0.97$$ ≥ 0.97 ) and good for the pachymetry difference maps (ICC $$\ge$$ ≥ 0.86). ICC, Sw, and CR showed excellent reproducibility of $$d_{TC}$$ d TC , with values of 0.95, 0.03, and 0.08, respectively. ICC, Sw, and CR showed good reproducibility of $$d_{PC}$$ d PC , with values of 0.89, 0.06, and 0.17, respectively. Conclusion The centration analysis method used in this study showed good to excellent repeatability and reproducibility in locating the coordinates of the center of the OZ on the tangential and pachymetry difference maps.

Abstract Prostate cancer (PRAD) is one of the leading malignancies in men all around the world. Here, we identified Myosin Heavy Chain 6 (MYH6) as a potential tumor suppressor gene in the development of prostate cancer. We found lower expression of MYH6 in prostate cancer tissues, and its lower gene expression was also associated with worse clinical outcomes. In vitro and in vivo assays indicated that overexpressed MYH6 could suppress the proliferation and migration progression of prostate cancer cells. RNA-seq was employed to investigate the mechanism, and KIT Proto-Oncogen (KIT) was determined as the downstream gene of MYH6, which was further confirmed using rescue assays. In all, we provide the evidence that MYH6 could serve as a tumor suppressor in prostate cancer. Our results highlight the potential role of MYH6 in the development of prostate cancer.

Abstract Photoacoustic tomography offers a powerful tool to visualize biologically relevant molecules and understand processes within living systems at high resolution in deep tissue, facilitated by the conversion of incident photons into low-scattering acoustic waves through non-radiative relaxation. Although current endogenous and exogenous photoacoustic contrast agents effectively enable molecular imaging within deep tissues, their broad absorption spectra in the visible to near-infrared (NIR) range limit photoacoustic multiplexed imaging. Here, we exploit the distinct ultrasharp NIR absorption peaks of lanthanides to engineer a series of NIR photoacoustic nanocrystals. This engineering involves precise host and dopant material composition, yielding nanocrystals with sharply peaked photoacoustic absorption spectra (~3.2 nm width) and a ~10-fold enhancement in NIR optical absorption for efficient deep tissue imaging. By combining photoacoustic tomography with these engineered nanocrystals, we demonstrate photoacoustic multiplexed differential imaging with substantially decreased background signals and enhanced precision and contrast.

Abstract Background Human adipose-derived stem cells (ADSCs) exert a strong anti-inflammatory effect, and synovium-derived stem cells (SDSCs) have high chondrogenic potential. Thus, this study aims to investigate whether a combination of human ADSCs and SDSCs will have a synergistic effect that will increase the chondrogenic potential of osteoarthritis (OA) chondrocytes in vitro and attenuate the cartilage degeneration of early and advanced OA in vitro. Methods ADSCs, SDSCs, and chondrocytes were isolated from OA patients who underwent total knee arthroplasty. The ADSCs–SDSCs mixed cell ratios were 1:0 (ADSCs only), 8:2, 5:5 (5A5S), 2:8, and 0:1 (SDSCs only). The chondrogenic potential of the OA chondrocytes was evaluated in vitro with a transwell assay or pellet culture with various mixed cell groups. The mixed cell group with the highest chondrogenic potential was then selected and injected into the knee joints of nude rats of early and advanced OA stages in vivo. The animals were then evaluated 12 and 20 weeks after surgery through gait analysis, von frey test, microcomputed tomography, MRI, and immunohistochemical and histological analyses. Finally, the mechanisms underlying these findings were investigated through the RNA sequencing of tissue samples in vivo and Western blot of the OA chondrocyte autophagy pathway. Results Among the MSCs treatment groups, 5A5S had the greatest synergistic effect that increased the chondrogenic potential of OA chondrocytes in vitro and inhibited early and advanced OA in vivo. The 5A5S group significantly reduced cartilage degeneration, synovial inflammation, pain sensation, and nerve invasion in subchondral nude rat OA, outperforming both single-cell treatments. The underlying mechanism was the activation of chondrocyte autophagy via the FoxO1 signaling pathway. Conclusion A combination of human ADSCs and SDSCs demonstrated higher potential than a single type of stem cell, demonstrating potential as a novel treatment for OA.

Abstract Late-stage specific and selective diversifications of peptides and proteins performed at target residues under ambient conditions are recognized to be the most facile route to various and abundant conjugates. Herein, we report an orthogonal modification of cysteine residues using alkyl thianthreium salts, which proceeds with excellent chemoselectivity and compatibility under mild conditions, introducing a diverse array of functional structures. Crucially, multifaceted bioconjugation is achieved through clickable handles to incorporate structurally diverse functional molecules. This “two steps, one pot” bioconjugation method is successfully applied to label bovine serum albumin. Therefore, our technique is a versatile and powerful tool for late-stage orthogonal bioconjugation.

Abstract High-precision Global Navigation Satellite System (GNSS) orbit and clock products are crucial for precise applications. An evenly distributed global network enables continuous tracking for GNSS satellites, while a regional network may result in tracking gaps in the areas where monitoring stations are not deployed. This also means that the orbit determination accuracy based on a regional network is not comparable to that with a global network. Integrating the measurements from regional ground stations and Low Earth Orbit (LEO) satellites onboard receivers is a potential approach for generating GNSS orbit and clock products with centimeter-level accuracy, which is particularly important for BDS and the local commercial providers relying on a regional network. In the integrated Precise Orbit Determination (POD), LEO satellites are used to compensate for the drawback of regional ground stations in the precise orbit and clock determination of GNSS satellites. To validate the role of LEO satellites in the orbit determination with a regional network, 6 International GNSS Service stations around China and 13 LEO satellites from January 20 to 26, 2019, including GRACE-C/D, SWARM-A/B/C, Jason-3, Sentinel-3A/B, and SAT-A/B/C/D/E are selected in this study to perform the integrated POD. The orbit and clock accuracies of GPS and LEO satellites are evaluated by comparison with precise products. The average Root Mean Square (RMS)of GPS orbit errors in the radial (R), along-track (T) and cross-track (N) directions are 2.27 cm, 3.45 cm, and 3.08 cm, respectively, and the clock accuracy is better than 0.15 ns based on a comparison with the final products provided by Center for Orbit Determination in Europe (CODE). The LEO orbit accuracy is better than 2 cm in the R direction, and the position errors are mostly within 4 cm. The results indicate that the integrated POD can generate high-precision orbit and clock products for GPS and LEO satellites based on regional network stations. Finally, the integrated POD products are assessed for Precise Point Positioning (PPP). Simulated kinematic PPP has a comparable performance in terms of the convergence time and positioning accuracy. With more LEO satellites available, the orbit and clock determination accuracy and PPP positioning accuracy can be improved.

Abstract Extreme myopia (EM), defined as a spherical equivalent (SE) ≤ −10.00 diopters (D), is one of the leading causes of sight impairment. Known EM-associated variants only explain limited risk and are inadequate for clinical decision-making. To discover risk genes, we performed a whole-exome sequencing (WES) on 449 EM individuals and 9606 controls. We find a significant excess of rare protein-truncating variants (PTVs) in EM cases, enriched in the retrograde vesicle-mediated transport pathway. Employing single-cell RNA-sequencing (scRNA-seq) and a single-cell polygenic burden score (scPBS), we pinpointed PI16 + /SFRP4+ fibroblasts as the most relevant cell type. We observed that KDELR3 is highly expressed in scleral fibroblast and involved in scleral extracellular matrix (ECM) organization. The zebrafish model revealed that kdelr3 downregulation leads to elongated ocular axial length and increased lens diameter. Together, our study provides insight into the genetics of EM in humans and highlights KDELR3’s role in EM pathogenesis.

To win a taekwondo competition, more points must be scored, and the key to scoring points is to improve the motor performance of the kick. However, the relationship between core stability and the effectiveness of athletic performance, particularly in executing the wing kick, remains ambiguous, impeding coaches and athletes in their efforts to improve athletic performance. A total of 26 male participants (height: 167.21 ± 7.29 cm; weight: 62.07 ± 8.03 kg; age: 24.69 ± 2.53 years) participated, and they have been practicing Taekwondo for more than 10 years. Kinematic and kinetic data were collected using 13 infrared cameras at 120 Hz, muscle activity data were collected using epidermal electromyography, and participants’ core stability level were measured using the Sahrmann Core Stability Test (SCST) for correlation with other variables. Core stability levels showed a strong negative correlation with execution time (r = −0.7144, p < 0.001) of the aerial phase of the wing kick as did angular momentum in most lower limb segments (thigh X axis, r = −0.6435, p < 0.001, shank X axis, r = −0.62008, p < 0.001, foot X axis, r = −0.7033, p < 0.001). Bilateral rectus abdominis (RA) showed strong correlations with muscle activation (left rectus abdominis (LRA) of left foot take off-left knee max extension (LTO-LKMF) phase, r = 0.5351, p < 0.001, right rectus abdominis (RRA) of LTO-LKMF phase, r = −0.5628, p < 0.001), and high levels of core stability were associated with better core-muscle coupling. We conclude that incorporating core stability training into taekwondo training has the potential to improve wing kick performance.

Wet deposition significantly impacts the basin ecosystem and water quality of the Qinling Mountains (QMs). However, few research focused on the difference in wet deposition between the northern (QN) and southern (QS) foothills due to the barrier effect of the QMs. This two-year investigation studied nutrient and organic matter deposition in QN and QS during summer and autumn. Results showed higher concentrations of nitrogen (N), phosphorus (P), dissolved organic carbon (DOC), and permanganate index (CODMn) in QN's rainwater, particularly in autumn. The CODMn in QN ranged 0.59–7.67 mg/L, and DOC ranged 0.64–4.45 mg/L. For QS, the CODMn ranged 0.71–3.25 mg/L, and DOC ranged 0.28–2.62 mg/L. Backward trajectory analysis revealed the accumulation of pollutants in QN originating from Northern China, intensified by autumn heating and straw burning. Tyrosine-like and humic-like components in rainwater DOM suggested that they primarily originated from autochthonous sources. Rainwater N:P mass ratios range from 39:1 to 145:1, highlighting a higher N input than P in QMs' wet deposition. The findings underscore the importance of atmospheric wet deposition in nutrient and organic matter input to the QMs and establish a foundation for exploring the ecological effects of wet deposition. HIGHLIGHTS Concentration of rainwater contaminant showed spatiotemporal variations.; The dilution effect significantly impacted volume-weighted mean concentration.; Higher rainwater pollutant concentrations due to higher atmospheric pollutant levels.; The proportion of N transported to the watershed was higher than that of C and P.;

Objective The upper Permian Wujiaping Formation in the Hongxing area of eastern Sichuan Province has good shale gas accumulation conditions and is also an important successor for Permian shale gas exploration in the Sichuan Basin. However, the formation mechanism of these siliceous-argillaceous source rocks is still unclear. Apart from their petromineralogical characteristics, geochemical composition and macrofossil assemblage (represented by radiolarian) are also important for identifying the genesis of this siliceous-argillaceous source rock. Methods Radiolarian is a significant planktonic component of the Phanerozoic marine ecosystem. Various radiolarian assemblages indicate different sedimentary environments, and their abundance is a good indicator of palaeoproductivity. In this study, radiolarians were separated by the acid-etching method to identify different morphological characteristics, and the correlation between radiolarian abundance and total organic carbon (TOC) content was also analysed through thin-section observation. Results A large number of radiolarians were found in the Wujiaping Formation in the Well HY3 in the Hongxing area of eastern Sichuan Province. These fossils were identified as Spumellaria and Entactinaria, belonging to a typical shallow-water radiolarian assemblage, namely, the Se assemblage. In the Second Member of the Wujiaping Formation, the radiolarian abundance exhibited a relatively positive correlation with the TOC content. Conclusion Based on the radiolarian assemblage characteristics, sedimentary sequence and palaeogeographic background of the Wujiaping Formation, it is inferred that these source rocks from the Second Member of the Wujiaping Formation formed in a shallow-water environment less than 60 m deep. The accumulation of organic matter in the Second Member of the Wujiaping Formation was probably affected by primary productivity, redox conditions, terrigenous debris input and upwelling, among which high palaeoproductivity was one of the main controlling factors.

Abstract Ubiquitination, a pivotal posttranslational modification of proteins, plays a fundamental role in regulating protein stability. The dysregulation of ubiquitinating and deubiquitinating enzymes is a common feature in various cancers, underscoring the imperative to investigate ubiquitin ligases and deubiquitinases (DUBs) for insights into oncogenic processes and the development of therapeutic interventions. In this review, we discuss the contributions of the ubiquitin–proteasome system (UPS) in all hallmarks of cancer and progress in drug discovery. We delve into the multiple functions of the UPS in oncology, including its regulation of multiple cancer-associated pathways, its role in metabolic reprogramming, its engagement with tumor immune responses, its function in phenotypic plasticity and polymorphic microbiomes, and other essential cellular functions. Furthermore, we provide a comprehensive overview of novel anticancer strategies that leverage the UPS, including the development and application of proteolysis targeting chimeras (PROTACs) and molecular glues.

Abstract The tumor microenvironment (TME) plays a pivotal role in the onset, progression, and treatment response of cancer. Among the various components of the TME, cancer-associated fibroblasts (CAFs) are key regulators of both immune and non-immune cellular functions. Leveraging single-cell RNA sequencing (scRNA) data, we have uncovered previously hidden and promising roles within this specific CAF subgroup, paving the way for its clinical application. However, several critical questions persist, primarily stemming from the heterogeneous nature of CAFs and the use of different fibroblast markers in various sample analyses, causing confusion and hindrance in their clinical implementation. In this groundbreaking study, we have systematically screened multiple databases to identify the most robust marker for distinguishing CAFs in lung cancer, with a particular focus on their potential use in early diagnosis, staging, and treatment response evaluation. Our investigation revealed that COL1A1, COL1A2, FAP, and PDGFRA are effective markers for characterizing CAF subgroups in most lung adenocarcinoma datasets. Through comprehensive analysis of treatment responses, we determined that COL1A1 stands out as the most effective indicator among all CAF markers. COL1A1 not only deciphers the TME signatures related to CAFs but also demonstrates a highly sensitive and specific correlation with treatment responses and multiple survival outcomes. For the first time, we have unveiled the distinct roles played by clusters of CAF markers in differentiating various TME groups. Our findings confirm the sensitive and unique contributions of CAFs to the responses of multiple lung cancer therapies. These insights significantly enhance our understanding of TME functions and drive the translational application of extensive scRNA sequence results. COL1A1 emerges as the most sensitive and specific marker for defining CAF subgroups in scRNA analysis. The CAF ratios represented by COL1A1 can potentially serve as a reliable predictor of treatment responses in clinical practice, thus providing valuable insights into the influential roles of TME components. This research marks a crucial step forward in revolutionizing our approach to cancer diagnosis and treatment.

Abstract Background Myocardial ischemia-reperfusion injury (MIRI) is defined as the restoration of blood flow to the myocardium after a brief interruption of blood supply, causing more severe damage to the ischemic myocardium. However, currently, reperfusion therapy is the preferred therapy for ischemic cardiomyopathy, which undoubtedly causes MIRI, and thus it has become a challenging issue affecting the prognosis of coronary artery disease. Methods A search was conducted in the Web of Science Core Collection database for papers relevant to MIRI therapy published between 1 January 2000 and 1 October 2023. Bibliometric analyses were performed using VOSviewer and CiteSpace to elucidate the progress and hotspots. Results 3304 papers from 64 countries, 2134 research institutions and 13,228 authors were enrolled in the study. Of these, China contributed the most papers and had the biggest impact, while the United States had the most extensive partnership. The Fourth Military Medical University was the primary research institution. The most valuable authors include Chattipakorn, Nipon, Chattipakorn, Siriporn c, Yang, Jian and Yang, Yang. Conclusion Over the past 20 years, research on MIRI therapies has made significant strides. Further studies are necessary to explore the interactions between various therapeutic options. Future investigations will emphasize nanocarriers, cardiac regeneration, and stem cell therapies. Our study identifies MIRI research hotspots from a bibliometric perspective, forecasts future trends, and offers fresh insights into MIRI therapy research.

Gradient triply periodic minimal surface (TPMS) structures are renowned for lightweight design and enhanced performance, but their complex and nonlinear configurations pose challenges in achieving targeted design goals. A new design methodology for the nonlinear gradient structure was proposed in this study, with the aim of achieving efficient and accurate modeling of complex and gradient sheet-based TPMS structures under specific performance objectives. This method utilized automated finite element (FE) simulations to obtain structure topology element densities under various boundary conditions. An artificial neural network (ANN) was then employed to efficiently predict the correspondence between these boundary conditions and topology element densities. A mapping was established between topology element densities and TPMS structural parameters, and the gradient structure was accurately constructed by using the voxel modeling technique. Taking a typical cantilever beam TPMS structure as an example of nonlinear gradient design, the results indicate that the error between the ANN-predicted and FE-simulated structure topology element densities is only 2.73 %, with prediction time being only 0.15 % of the simulation time. The thin regions of the gradient structure align with those geometrically removed in regular topology optimization scheme, achieving up to 65.45 % weight reduction, a 28.72 % improvement over the regular scheme, along with uniform structural stress transition and maximum stress reduction. TC4 alloy nonlinear gradient TPMS structures, printed by metal selective laser melting (SLM) technique, confirm the practical application value of this design method.

Volatile components in red orange essential oil extracted by two cold pressing processes (cup pressing and lime method) were analyzed by gas chromatography quadrupole time-of-flight mass spectrometry (GC-Q/TOF). A total of 93 components were identified, 89 and 84 compounds were identified for the two types of red orange essential oils, respectively. Among the 93 components, there were 29 terpenes, 20 alcohols, 20 aldehydes, 5 esters, 2 ketones, 12 hydrocarbons, and 5 other compounds. There were 80 compounds shared by the two essential oils. The total volatile component content of red orange essential oil by cup pressing method was significantly higher than that by lime method. The highest content of these compounds was terpenes which total content was over 80%. In addition, the compounds with higher content were D-limonene, γ-terpinene, β-myrcene, linalool and α-pinene. According to principal component analysis (PCA), there was a significant difference in the volatile components of the two types of red orange essential oils. The relative odor activity value (ROAV) method indicated that linalool was the most important aroma component of the two red orange essential oils. And the citrus aroma properties of red orange essential oil extracted by cup pressing method was significantly stronger than that extracted by lime method. Linalool, thymol, β-myrcene, D-limonene, citronellal, and γ-terpinene were confirmed to the key aroma components of the red orange essential oils.

Abstract ADGRF5 (GPR116) has been identified as a facilitator of breast cancer cell migration and metastasis, yet the underlying mechanisms remain largely elusive. Our current study reveals that the absence of ADGRF5 in breast cancer cells impairs extracellular matrix (ECM)-associated cell motility and impedes in vivo tumor growth. This correlates with heightened expression of matrix metalloproteinase 8 (MMP8), a well-characterized antitumorigenic MMP, and a shift in the polarization of tumor-associated neutrophils (TANs) towards the antitumor N1 phenotype in the tumor microenvironment (TME). Mechanistically, ADGRF5 inhibits ERK1/2 activity by enhancing RhoA activation, leading to decreased phosphorylation of C/EBPβ at Thr235, hindering its nuclear translocation and subsequent activation. Crucially, two C/EBPβ binding motifs essential for MMP8 transcription are identified within its promoter region. Consequently, ADGRF5 silencing fosters MMP8 expression and CXCL8 secretion, attracting increased infiltration of TANs; simultaneously, MMP8 plays a role in decorin cleavage, which leads to trapped-inactivation of TGF-β in the TME, thereby polarizing TANs towards the antitumor N1 neutrophil phenotype and mitigating TGF-β-enhanced cell motility in breast cancer. Our findings reveal a novel connection between ADGRF5, an adhesion G protein-coupled receptor, and the orchestration of the TME, which dictates malignancy progression. Overall, the data underscore ADGRF5 as a promising therapeutic target for breast cancer intervention.

Abstract Blood group is a potential genetic element in coronary artery disease. Nevertheless, the relationship between different ABO blood groups and myocardial injury after non-cardiac surgery (MINS) is poorly understood. This study verified whether ABO blood group is a potential MINS influencing factor. This retrospective cohort study included 1201 patients who underwent elective non-cardiac surgery and a mandatory troponin test on postoperative days 1 and 2 from 2019 to 2020 at a university-affiliated tertiary hospital. The primary outcome was associations between ABO blood groups and MINS, assessed using univariate and multivariate logistic-regression analyses. Path analysis was used to investigate direct and indirect effects between blood group and MINS. MINS incidence (102/1201, 8.5%) was higher in blood-type B patients than in non-B patients [blood-type B: 44/400 (11.0%) vs. non-B: 58/801 (7.2%); adjusted odds ratio = 1.57 (1.03–2.38); p = 0.036]. In the confounding factor model, preoperative hypertension and coronary artery disease medical history were associated with MINS risk [adjusted odds ratio: 2.00 (1.30–3.06), p = 0.002; 2.81 (1.71–4.61), p

Abstract This paper presents a frequency selective surface (FSS) with a wideband second-order bandpass response in the dual-band of microwave and millimeter wave. The overall structure consists of three layers of metal pattern and two layers of thin dielectric substrate. The top and bottom metal layers have capacitive patches with integrated curled Jerusalem cross slot resonators, while the intermediate metal layer has an inductive grid structure with cross-shaped slot resonators. The incorporated slot resonators play a pivotal role in achieving the desired transmission poles or zeros, which enable a wideband second-order filtering response in the dual-band and a quick roll-off at the passband edges, increasing the efficacy of electromagnetic shielding. To fully investigate the structure's frequency response, an equivalent circuit model of the structure is created, spanning the complete frequency range of 5–50 GHz. Physical samples are created and measured to confirm the suggested approach’s efficacy. The passband center frequencies of the FSS are found at f 1 = 19.42 GHz and f 2 = 42.78 GHz, and the − 3 dB bandwidth is 4.34 GHz (17.25–21.59 GHz) and 8.54 GHz (38.51–47.05 GHz), respectively. The simulation results align well with the experimental data. The transmission response rapidly transitions from the passband to the stopband at the passband boundaries.

Abstract In higher plants, mature male gametophytes have distinct apertures. After pollination, pollen grains germinate, and a pollen tube grows from the aperture to deliver sperm cells to the embryo sac, completing fertilization. In rice, the pollen aperture has a single-pore structure with a collar-like annulus and a plug-like operculum. A crucial step in aperture development is the formation of aperture plasma membrane protrusion (APMP) at the distal polar region of the microspore during the late tetrad stage. Previous studies identified OsINP1 and OsDAF1 as essential regulators of APMP and pollen aperture formation in rice, but their precise molecular mechanisms remain unclear. We demonstrate that the Poaceae-specific OsSRF8 gene, encoding a STRUBBELIG-receptor family 8 protein, is essential for pollen aperture formation in Oryza sativa. Mutants lacking functional OsSRF8 exhibit defects in APMP and pollen aperture formation, like loss-of-function OsINP1 mutants. OsSRF8 is specifically expressed during early anther development and initially diffusely distributed in the microsporocytes. At the tetrad stage, OsSRF8 is recruited by OsINP1 to the pre-aperture region through direct protein-protein interaction, promoting APMP formation. The OsSRF8-OsINP1 complex then recruits OsDAF1 to the APMP site to co-regulate annulus formation. Our findings provide insights into the mechanisms controlling pollen aperture formation in cereal species.

Abstract The Rho GTPase activating protein family (ARHGAPs) is expressed in pancreatic adenocarcinoma (PAAD) but its function is unclear. The aim of this study was to explore the role and potential clinical value of ARHGAPs in PAAD. Using TCGA and GEO databases to analyze expression of ARHGAPs in PAAD and normal tissues. Survival curve was drawn by Kaplan–Meier. ARHGAPs were integrated analyzed by GEPIA2, TIMER, UCLCAN, cBioPortal and R language. Protein level and prognostic value were evaluated via IHC staining or survival analysis. We totally identify 18 differentially expressed (DE) ARHGAPs in PAAD. Among the 18 DE genes, 8 were positively correlated with tumor grade; abnorrmal expression of 5 was positively correlated with copy number variation; expression of 4 was positively correlated with promoter hypomethylation. Multivariate Cox regression identified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors of PAAD. The function of ARHGAPs was mainly related to GTPase activity and signaling, axon guidance, proteoglycans in cancer and focal adhesion. Expression of 7 ARHGAPs was strongly correlated with immune infiltration. Immunohistochemistry showed increased protein levels of ARHGAP5, ARHGAP11A, and ARHGAP12 in PAAD tissues. Survival analysis confirmed a negative correlation between ARHGAP5, ARHGAP11A, and ARHGAP12 expression and patient prognosis. Multivariate Cox regression proved ARHGAP5, ARHGAP11A, and ARHGAP12 could serve as independent prognostic indicators for PAAD. Finally, this study verified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors in PAAD, suggesting their significance for the diagnosis and treatment of PAAD.

Abstract N6-methyladenosine (m6A) stands as the most prevalent modified form of RNA in eukaryotes, pivotal in various biological processes such as regulating RNA stability, translation, and transcription. All members within the YT521-B homology (YTH) gene family are categorized as m6A reading proteins, capable of identifying and binding m6A modifications on RNA, thereby regulating RNA metabolism and functioning across diverse physiological processes. YTH domain-containing 2 (YTHDC2), identified as the latest member of the YTH family, has only recently started to emerge for its biological function. Numerous studies have underscored the significance of YTHDC2 in human physiology, highlighting its involvement in both tumor progression and non-tumor diseases. Consequently, this review aims to further elucidate the pathological mechanisms of YTHDC2 by summarizing its functions and roles in tumors and other diseases, with a particular focus on its downstream molecular targets and signaling pathways.

Abstract In clinical settings, tumor compression, trauma, surgical injury, and other types of injury can cause hypothalamic damage, resulting in various types of hypothalamic dysfunction. Impaired release of oxytocin can lead to cognitive impairment and affect prognosis and long-term quality of life after hypothalamic injury. Hypothalamic injury-induced cognitive dysfunction was detected in male animals. Behavioral parameters were measured to assess the characteristics of cognitive dysfunction induced by hypothalamic–pituitary stalk lesions. Brains were collected for high-throughput RNA sequencing and immunostaining to identify pathophysiological changes in hippocampal regions highly associated with cognitive function after injury to corresponding hypothalamic areas. Through transcriptomic analysis, we confirmed the loss of oxytocin neurons after hypothalamic injury and the reversal of hypothalamic-induced cognitive dysfunction after oxytocin supplementation. Furthermore, overactivation of the ERK signaling pathway and β-amyloid deposition in the hippocampal region after hypothalamic injury were observed, and cognitive function was restored after inhibition of ERK signaling pathway overactivation. Our findings suggest that cognitive dysfunction after hypothalamic injury may be caused by ERK hyperphosphorylation in the hippocampal region resulting from a decrease in the number of oxytocin neurons, which in turn causes β-amyloid deposition.

Abstract Gastrointestinal (GI) disruptions and inflammatory bowel disease (IBD) are commonly associated with Parkinson’s disease (PD), but how they may impact risk for PD remains poorly understood. Herein, we provide evidence that prodromal intestinal inflammation expedites and exacerbates PD endophenotypes in rodent carriers of the human PD risk allele LRRK2 G2019S in a sex-dependent manner. Chronic intestinal damage in genetically predisposed male mice promotes α-synuclein aggregation in the substantia nigra, loss of dopaminergic neurons and motor impairment. This male bias is preserved in gonadectomized males, and similarly conferred by sex chromosomal complement in gonadal females expressing human LRRK2 G2019S. The early onset and heightened severity of neuropathological and behavioral outcomes in male LRRK2 G2019S mice is preceded by increases in α-synuclein in the colon, α-synuclein-positive macrophages in the colonic lamina propria, and loads of phosphorylated α-synuclein within microglia in the substantia nigra. Taken together, these data reveal that prodromal intestinal inflammation promotes the pathogenesis of PD endophenotypes in male carriers of LRRK2 G2019S, through mechanisms that depend on genotypic sex and involve early accumulation of α-synuclein in myeloid cells within the gut.

Abstract Background Reintroduction represents an effective strategy for the conservation of endangered wildlife, yet it might inadvertently impact the native ecosystems. This investigation assesses the impact of reintroducing endangered Przewalski's horses into the desert grassland ecosystem of the Kalamaili Nature Reserve (KNR), particularly its effect on the spatial distribution of ticks. In a 25 km2 core area of Przewalski's horse distribution, we set up 441 tick sampling sites across diverse habitats, including water sources, donkey trails, and grasslands, recording horse feces and characteristics to analyze the occurrence rate of ticks. Additionally, we gathered the data of 669 fresh feces of horses. To evaluate the spatial dynamics between these feces and ticks, we used methods such as Fixed Kernel Estimation (FKE), Moran’s I spatial autocorrelation index, and Generalized Linear Models (GLM). Results The dominant species of ticks collected in the core area were adult Hyalomma asiaticum (91.36%). Their occurrence rate was higher near donkey trails (65.99%) and water sources (55.81%), particularly in areas with the fresh feces of Przewalski's horses. The ticks’ three risk areas, as defined by FKE, showed significant overlap and positive correlation with the distribution of Przewalski's horses, with respective overlap rates being 90.25% in high risk, 33.79% in medium risk, and 23.09% in low risk areas. Moran's I analysis revealed a clustering trend of the fresh feces of Przewalski's horses in these areas. The GLM confirmed a positive correlation between the distribution of H. asiaticum and the presence of horse fresh feces, alongside a negative correlation with the proximity to water sources and donkey trails. Conclusions This study reveals the strong spatial correlation between Przewalski's horses and H. asiaticum in desert grasslands, underlining the need to consider interspecific interactions in wildlife reintroductions. The findings are crucial for shaping effective strategies of wildlife conservation and maintaining ecological balance.

Abstract The “terminal hydroxyl group anchoring mechanism” has been studied on metal oxides (Al2O3, CeO2) as well as a variety of noble and transition metals (Ag, Pt, Pd, Cu, Ni, Fe, Mn, and Co) in a number of generalized studies, but there is still a gap in how to regulate the content of terminal hydroxyl groups to influence the dispersion of the active species and thus to achieve optimal catalytic performance. Herein, we utilized AlOOH as a precursor for γ-Al2O3 and induced the transformation of the exposed crystal face of γ-Al2O3 from (110) to (100) by controlling the calcination temperature to generate more terminal hydroxyl groups to anchor Ag species. Experimental results combined with AIMD and DFT show that temperature can drive the atomic rearrangement on the (110) crystal face, thereby forming a structure similar to the atomic arrangement of the (100) crystal face. This resulted in the formation of more terminal hydroxyl groups during the high-temperature calcination of the support (Al-900), which can capture Ag species to form single-atom dispersions, and ultimately develop a stable and efficient single-atom Ag-based catalyst.

Avian metapneumovirus (aMPV) is a highly contagious pathogen that causes acute upper respiratory tract diseases in chickens and turkeys, resulting in serious economic losses. Subtype B aMPV has recently become the dominant epidemic strain in China. We developed an attenuated aMPV subtype B strain by serial passaging in Vero cells and evaluated its safety and efficacy as a vaccine candidate. The safety test showed that after the 30th passage, the LN16-A strain was fully attenuated, as clinical signs of infection and histological lesions were absent after inoculation. The LN16-A strain did not revert to a virulent strain after five serial passages in chickens. The genomic sequence of LN16-A differed from that of the parent wild-type LN16 (wtLN16) strain and had nine amino acid mutations. In chickens, a single immunization with LN16-A induced robust humoral and cellular immune responses, including the abundant production of neutralizing antibodies, CD4+ T lymphocytes, and the Th1 (IFN-γ) and Th2 (IL-4 and IL-6) cytokines. We also confirmed that LN16-A provided 100% protection against subtype B aMPV and significantly reduced viral shedding and turbinate inflammation. Our findings suggest that the LN16-A strain is a promising live attenuated vaccine candidate that can prevent infection with subtype B aMPV.

Sugarcane is the most vital sugar crop in China, with excellent nutritional, medicinal and economic value. Sugarcane is rich in phenolic compounds, which have a variety of physiological functions, such as antioxidant, anti-inflammatory, and hypoglycemic. This paper focuses on the extraction of sugarcane polyphenols and the application of novel extraction techniques to plant polyphenols. In addition, principles and properties of purification methods for sugarcane polyphenols are presented, and important biological activities including antioxidant, hypoglycaemic, anti-inflammatory, anti-cancer and anti-bacterial properties are described. The extraction and purification of sugarcane polyphenols is found to be relatively routine. Although sugarcane polyphenols have a variety of biological activities, the mechanisms of their activity have not been fully elucidated. There is a need to focus on new extraction and purification techniques for sugarcane polyphenols and mechanisms of their activity to facilitate the development and utilization of sugarcane polyphenols and deep processing of sugarcane byproducts.

Prostate cancer is a prevalent malignancy and leading cause of male mortality worldwide, thus highlighting the need for precision medicine and a combined single-cell and bulk transcriptome-based diagnostic assessment model. First, we used single-cell RNA sequencing data and the high dimensional weighted gene co-expression network analysis (hdWGCNA) method to identify specific cell types in tumor tissues. We identified higher proportions of epithelial cells and increased intra-tissue heterogeneity in prostate cancer; most of these epithelial cells were closely associated with metal ion transport functions. Lasso regression identified diagnostic-related genes that were incorporated into a sample evaluation model using multiple machine learning algorithms. Thus, we established a diagnostic model that combined immune cells, diagnostic genes and deep learning methods. The Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) models exhibited the highest diagnostic efficacy for Lasso genes. Neural network models, combining immune microenvironment assessment and diagnostic gene expression, also showed good diagnostic efficacy. Our study highlights the potential of machine learning and convolutional neural networks for the diagnostic assessment of prostate cancer, thus providing support for personalized treatment decisions, and identifying areas for future research.

Abstract Syndecan-binding protein (SDCBP) was reported to stimulate the advancement of esophageal squamous cell carcinoma (ESCC) and could potentially be a target for ESCC treatment. There is a growing corpus of research on the anti-tumor effects of iron chelators; however, very few studies have addressed the involvement of dexrazoxane in cancer. In this study, structure-based virtual screening was employed to select drugs targeting SDCBP from the Food and Drug Administration (FDA)-approved drug databases. The sepharose 4B beads pull-down assay revealed that dexrazoxane targeted SDCBP by interacting with its PDZ1 domain. Additionally, dexrazoxane inhibited ESCC cell proliferation and anchorage-independent colony formation via SDCBP. ESCC cell apoptosis and G2 phase arrest were induced as measured by the flow cytometry assay. Subsequent research revealed that dexrazoxane attenuated the binding ability between SDCBP and EGFR in an immunoprecipitation assay. Furthermore, dexrazoxane impaired EGFR membrane localization and inactivated the EGFR/PI3K/Akt pathway. In vivo, xenograft mouse experiments indicated that dexrazoxane suppressed ESCC tumor growth. These data indicate that dexrazoxane might be established as a potential anti-cancer agent in ESCC by targeting SDCBP.

Abstract This work presents a novel tri-band bandpass frequency selective surface (FSS) that achieves high-order filtering responses in different frequency bands by means of a complementary structure. The proposed FSS is composed of three metal periodic arrays, which are separated by multilayer dielectric substrates. The gridded-double convoluted loop (G-DCL) structure, which is the middle layer structure, is a hybrid resonator that generates different resonant frequencies. The top and bottom layer structures are designed as complementary structures to the middle layer. To accurately describe the frequency responses, an equivalent circuit model (ECM) has been constructed over the entire band from 0 to 16 GHz. The results of the simulation indicate that the developed FSS can generate three pass-bands operating at 3.79 GHz, 8.34 GHz, and 12.52 GHz, respectively, and − 3 dB fractional bandwidths are 52.8%, 13.7%, and 19.7%. The transmission responses at the edges of each passband show a quick roll-off from the passband to the stopband, and there is significant out-of-band suppression between adjacent passbands. Moreover, the FSS maintains excellent angular and polarization stability within a 50° range. For verification, the tri-band FSS has been fabricated and tested. The experimental results match the simulation results, validating the accuracy of the FSS design.

Abstract Persistent free radicals (PFRs) are emerging substances with diverse impacts in biochar applications, necessitating accurate prediction of their content and types prior to their optimal use and minimal adverse effects. This prediction task is challenging due to the nonlinearity and intricate variable relationships of biochar. Herein, we employed data-driven techniques to compile a dataset from peer-reviewed publications, aiming to systematically predict the PFRs by developing supervised machine learning models. Notably, extreme gradient boosting (XGBoost) model exhibited the best predictive performance for both regression and classification tasks in predicting the PFRs, achieving a test R2 value of 0.95 for PFR content prediction, along with an Area Under the Receiver Operating Curve (AUROC) of 0.92 for PFR type prediction, respectively. Based on XGBoost model, a graphical user interface (GUI) was developed to access PFRs predictions. Analysis of feature importance revealed that the biochar properties, such as metal/non-metal doping, pyrolysis temperature, carbon content, and specific surface area were identified as the four most significant factors influencing PFRs contents. Regarding the types of PFRs in biochar, specific surface area, pyrolysis temperature, carbon content, and feedstock were top-ranked influencing factors. These findings provide valuable guidance for accurately predicting both the contents and types of PFRs in biochar, and also hold significant potential for highly efficient utilization of biochar across various applications. Graphical Abstract

Establishing a multi-enzyme synergistic lignocellulosic biodegradation system using lytic polysaccharide monooxygenase (LPMO) and polyphenol oxidases is vital for efficiently utilizing plant biomass waste, ultimately benefiting the carbon cycle and promoting environmental protection. Single-residue mutations of LPMO can improve the efficiency of lignocellulosic biomass degradation. However, the activity of mutant-type LPMO in relation to lignin-diverted reducing agents has not been sufficiently explored. In this study, laccase and tyrosinase were initially investigated and their optimal conditions and impressive thermal stability were revealed, indicating their potential synergistic abilities with LPMO in lignocellulose biodegradation. When utilizing gallic acid as a reducing agent, the activities of LPMOs were increased by over 10%, which was particularly evident in mutant-type LPMOs after the addition of polyphenol oxidases. In particular, the combination of tyrosinase with either 4-hydroxy-3-methoxyphenylacetone or p-coumaric acid was shown to enhance the efficacy of LPMOs. Furthermore, the highest activity levels of wild-type LPMOs were observed with the addition of laccase and 3-methylcatechol. The similarities between wild and mutant LPMOs regarding their activities in lignin-diverted phenolic compounds and reducing agents are almost identical, suggesting that the single-residue mutation of LPMO does not have a detrimental effect on its performance. Above all, this study indicates that understanding the performance of both wild and mutant types of LPMOs in the presence of polyphenol oxidases and various reducing agents constitutes a key link in the industrialization of the multi-enzyme degradation of lignocellulose.

Abstract N6-methyladenosine (m6A) is important in regulating mRNA stability, splicing, and translation, and it also contributes to tumor development. However, there is still limited understanding of the comprehensive effects of m6A modification patterns on the tumor immune microenvironment, metabolism, and drug resistance in hepatocellular carcinoma (HCC). In this study, we utilized unsupervised clustering based on the expression of 23 m6A regulators to identify m6A clusters. We identified differential m6A modification patterns and characterized m6A-gene-cluster A, which exhibited poorer survival rates, a higher abundance of Treg cells, and increased expression of TGFβ in the tumor microenvironment (TME). Additionally, m6A-gene-cluster A demonstrated higher levels of glycolysis activity, cholesterol metabolism, and fatty acid biosynthesis. We also found that the m6A score was associated with prognosis and drug resistance. Patients with a low m6A score experienced worse prognoses, which were linked to an abundance of Treg cells, upregulation of TGFβ, and increased metabolic activity. HCC patients with a higher m6A score showed improved prognosis following sorafenib treatment and immunotherapy. In conclusion, we reveals the association between m6A modification patterns and the tumor immune microenvironment, metabolism, and drug resistance in HCC. Furthermore, the m6A score holds potential as a predictive factor for the efficacy of targeted therapy and immunotherapy in HCC.

Abstract Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p

Spinal cord ischemic-reperfusion injury (SCIRI) could occurs during surgical procedures without detection, presenting a complex course and an unfavorable prognosis. This may lead to postoperative sensory or motor dysfunction in areas innervated by the spinal cord, and in some cases, permanent paralysis. Timely detection of SCIRI and immediate waring can help surgeons implement remedial intervention to prevent irreversible spinal cord injury. Therefore, it is crucial to develop a precise and effective method for early detection of SCIRI. This study utilized rat models to simulate intraoperative SCIRI and employed somatosensory evoked potentials (SEP) for continuous monitoring during surgery. In this study, SEP signal changes were examined in six groups with varying severities of SCIRI and one normal control group. SEP signal changes were examined during operations in different groups and correlated with postoperative behavioral and histopathological data. The result demonstrated specific changes in SEP signals during SCIRI, termed as time-varying characteristics, which are associated with the duration of ischemia and subsequent reperfusion. Time-varying characteristics in SEP could potentially serve as a new biomarker for the intraoperative detection of SCIRI. This finding is significant for clinical surgeons to identify and guide early intervention of SCIRI timely. Additionally, this measurement is easily translatable to clinical application.

Avian reoviruses (ARVs) cause viral arthritis or tenosynovitis, resulting in poor weight gain and increased feed conversion ratios in chickens. In this study, we generated three Marek’s disease virus (MDV) recombinants, namely, rMDV-ARV-σB, rMDV-ARV-σC, and rMDV-ARV-σB + C, expressing ARV σB, σC, and both σB and σC, respectively. In rMDV-ARV-σB and rMDV-ARV-σC, the σB or σC gene was inserted into the US2 gene of MDV vaccine strain 814 using a fosmid-based rescue system. In rMDV-ARV-σB + C, the σB and σC genes were cloned into different expression cassettes, which were co-inserted into the US2 gene of the MDV 814 strain. In infected chicken embryo fibroblasts (CEFs), the recombinant virus rMDV-ARV-σB expressed σB, rMDV-ARV-σC expressed σC, and the rMDV-ARV-σB + C virus simultaneously expressed σB and σC. These recombinant viruses exhibited growth kinetics in CEFs similar to those of the parent MDV, and the inserted genes were stably maintained and expressed in the recombinant MDVs after 20 passages in cell cultures. These recombinant MDVs expressing σB and σC will provide potential vaccines against ARV infection in chickens.

The development of tissue engineering and regeneration research has created new platforms for bone transplantation. However, the preparation of scaffolds with good fiber integrity is challenging, because scaffolds prepared by traditional printing methods are prone to fiber cracking during solvent evaporation. Human skin has an excellent natural heat-management system, which helps to maintain a constant body temperature through perspiration or blood-vessel constriction. In this work, an electrohydrodynamic-jet 3D-printing method inspired by the thermal-management system of skin was developed. In this system, the evaporation of solvent in the printed fibers can be adjusted using the temperature-change rate of the substrate to prepare 3D structures with good structural integrity. To investigate the solvent evaporation and the interlayer bonding of the fibers, finite-element analysis simulations of a three-layer microscale structure were carried out. The results show that the solvent-evaporation path is from bottom to top, and the strain in the printed structure becomes smaller with a smaller temperature-change rate. Experimental results verified the accuracy of these simulation results, and a variety of complex 3D structures with high aspect ratios were printed. Microscale cracks were reduced to the nanoscale by adjusting the temperature-change rate from 2.5 to 0.5 °C s−1. Optimized process parameters were selected to prepare a tissue engineering scaffold with high integrity. It was confirmed that this printed scaffold had good biocompatibility and could be used for bone-tissue regeneration. This simple and flexible 3D-printing method can also help with the preparation of a wide range of micro- and nanostructured sensors and actuators.

ObjectiveTo investigate the impact of SRs-related genes on the overall survival and prognosis of osteosarcoma patients through bulk and single-cell RNA-seq transcriptome analysis.MethodsIn this study, we constructed a prognosis model based on serine/arginine-rich splicing factors (SRs) and predicted the survival of osteosarcoma patients. By analyzing single-cell RNA sequencing data and applying AUCell enrichment analysis, we revealed oncogenic pathways of SRs in osteosarcoma immune cells. Additionally, we described the regulatory role of SRSF7 in pan-cancer.ResultsLasso regression analysis identified 6 key SRs-related genes, and a prognosis prediction model was established. The upregulation of these pathways revealed that SRs promote tumor cell proliferation and survival by regulating related signaling pathways and help tumor cells evade host immune surveillance. Additionally, by grouping single-cell data using AUCell, we found significant differences in T cell expression between high and low-risk groups. The analysis results indicated that the regulatory activity of SRs is closely related to T cell function, particularly in regulating immune responses and promoting immune evasion. Furthermore, SRSF7 regulates cell proliferation and apoptosis.ConclusionSRs-related genes play a critical regulatory role in osteosarcoma. T cells are key in regulating immune responses and promoting immune evasion through SRs genes. SRSF7 is a significant gene influencing the occurrence and development of osteosarcoma.

Biomass-related airborne fine particulate matter (PM2.5) is an important risk factor for chronic obstructive pulmonary disease (COPD). Macrophage polarization has been reported to be involved in PM2.5-induced COPD, but the dynamic characteristics and underlying mechanism of this process remain unclear. Our study established a PM2.5-induced COPD mouse model and revealed that M2 macrophages predominantly presented after 4 and 6 months of PM2.5 exposure, during which a notable increase in MMP12 was observed. Single cell analysis of lung tissues from COPD patients and mice further revealed that M2 macrophages were the dominant macrophage subpopulation in COPD, with MMP12 being involved as a hub gene. In vitro experiments further demonstrated that PM2.5 induced M2 polarization and increased MMP12 expression. Moreover, we found that PM2.5 increased IL-4 expression, STAT6 phosphorylation and nuclear translocation. Nuclear pSTAT6 then bound to the MMP12 promoter region. Furthermore, the inhibition of STAT6 phosphorylation effectively abrogated the PM2.5-induced increase in MMP12. Using a coculture system, we observed a significantly reduced level of E-cadherin in alveolar epithelial cells cocultured with PM2.5-exposed macrophages, while the decrease in E-cadherin was reversed by the addition of an MMP12 inhibitor to the co-culture system. Taken together, these findings indicated that PM2.5 induced M2 macrophage polarization and MMP12 upregulation via the IL-4/STAT6 pathway, which resulted in alveolar epithelial barrier dysfunction and excessive extracellular matrix (ECM) degradation, and ultimately led to COPD progression. These findings may help to elucidate the role of macrophages in COPD, and suggest promising directions for potential therapeutic strategies.

Spatial patterns and environmental gradients in plant traits can elucidate the relationships between plant characteristics, environmental factors, and ecosystem functions and can be used to develop the next generation of vegetation models for predicting vegetation distribution and functions. Studies of Plant traits across spatial scales have advanced significantly worldwide, including on the Tibetan Plateau (TP), the highest and largest plateau globally. Previous research on plant traits on the TP has been limited to specific areas, leaving the overall trend across the plateau unclear. In this study, we examined seven leaf traits—leaf thickness (LT), leaf dry matter content (LDMC), leaf area (LA), specific leaf area (SLA), and leaf carbon (LCC), nitrogen (LNC), and phosphorus (LPC) contents—in 1314 individuals at 237 sites within the alpine vegetation region above 3000 m on the TP to determine their distribution patterns across three spatial dimensions and their relationships with environmental factors. Our results indicated that, compared with Chinese plants, TP plants exhibited significantly greater LT, LDMC, and LNC but lower LA, LCC, and LPC. Except for SLA and LCC, most leaf traits showed significant spatial variability. Climate and soil explained 29.23 % of the total variations in traits. Radiation had the most pronounced effect on LDMC, LA, LNC, and LPC, whereas soil pH primarily constrained LT and LCC. Precipitation influenced most traits both directly and indirectly, with substantial overall effects. Temperature and soil nutrient had minimal influence on the regulation of leaf traits across most of the TP. Our findings suggest that alpine plants typically employ a conservative strategy to cope with the harsh conditions on the TP, but this strategy varies at broader spatial scales and longer environmental gradients, particularly in extreme environments such as the highest alpine regions.

Abstract Liver fibrosis is a chronic pathological condition lacking specific clinical treatments. Stem cells, with notable potential in regenerative medicine, offer promise in treating liver fibrosis. However, stem cell therapy is hindered by potential immunological rejection, carcinogenesis risk, efficacy variation, and high cost. Stem cell secretome‐based cell‐free therapy offers potential solutions to address these challenges, but it is limited by low delivery efficiency and rapid clearance. Herein, an innovative approach for in situ implantation of smart microneedle (MN) arrays enabling precisely controlled delivery of multiple therapeutic agents directly into fibrotic liver tissues is developed. By integrating cell‐free and platinum‐based nanocatalytic combination therapy, the MN arrays can deactivate hepatic stellate cells. Moreover, they promote excessive extracellular matrix degradation by more than 75%, approaching normal levels. Additionally, the smart MN arrays can provide hepatocyte protection while reducing inflammation levels by ≈70–90%. They can also exhibit remarkable capability in scavenging almost 100% of reactive oxygen species and alleviating hypoxia. Ultimately, this treatment strategy can effectively restrain fibrosis progression. The comprehensive in vitro and in vivo experiments, supplemented by proteome and transcriptome analyses, substantiate the effectiveness of the approach in treating liver fibrosis, holding immense promise for clinical applications.

IntroductionThere exists a knowledge gap concerning the clinical significance of miRNA-21; therefore, in the present study, we aimed to estimate the diagnostic and prognostic accuracy and sensitivity of miRNA-21 in acute myocardial infarction (AMI) by performing an evidence-based meta-analysis of previous AMI-related clinical studies.MethodsChinese and English literature published before April 2024 were searched, and data were reviewed and extracted. After quality appraisal, the STATA 16.0 software was used for the effect size analysis of the various treatments described in the literature.ResultsA total of 14 valid documents were retrieved from 562 studies. The results of the systematic review revealed that for the patients with AMI vs. those without non-AMI, the aggregated odds ratio reached 5.37 (95% confidence interval 3.70–7.04). The general sensitivity and specificity for the circulating miRNA-21 levels in diagnosing AMI were 0.83 and 0.81, respectively.DiscussionThus, the meta-analysis of 14 AMI-related clinical trials highlighted that miRNA-21 may serve as a promising biomarker for diagnosing AMI.

Vehicle exhaust is one of the major organic sources in urban areas. Old taxis equipped with failed three-way catalysts (TWCs) have been regarded as “super emitters”. Compressed natural gas (CNG) is a regular substitution fuel for gasoline in taxis. The relative effect of fuel substitution and TWC failure has not been thoroughly investigated. In this work, vehicle exhausts from gasoline and CNG taxis with optimally functioning and malfunctioning TWCs are sampled by Tenax TA tubes and then analyzed by a comprehensive two-dimensional gas chromatography-mass spectrometer (GC×GC–MS). A total of 216 organics are quantified, including 80 volatile organic compounds (VOCs) and 132 intermediate volatility organic compounds (IVOCs). Failure of TWC introduces super emitters with 30 – 70 times emission factors (EFs), 60 – 112 times ozone formation potentials (OFPs), and 34 – 92 times secondary organic aerosols (SOAs) more than normal vehicles. Specifically, for the taxi with failed TWC, the total organic EF of CNG is 16 times that of gasoline, indicating that the failure of TWC exceeds the emission reduction achieved by CNG-gasoline substitution. A significant but unbalanced reduction of ozone and SOA is observed after TWC, whereas a notable “enrichment” in IVOCs was observed. Naphthalene is a typical IVOC component strongly associated with CNG-gasoline substitution and TWC failure, which is lacking in current VOC measurement. We especially emphasize that there is an urgent need to scrap vehicles with failed TWCs in order to significantly reduce air pollution.

IntroductionMetabolic syndrome (MetS) is significantly associated with osteoarthritis (OA), especially in MetS patients with blood glucose abnormalities, such as elevated fasting blood glucose (FG), which may increase OA risk. Dietary modifications, especially the intake of polyunsaturated fatty acids (PUFAs), are regarded as a potential means of preventing MetS and its complications. However, regarding the effects of FG, Omega-3s, and Omega-6s on OA, the research conclusions are conflicting, which is attributed to the complexity of the pathogenesis of OA. Therefore, it is imperative to thoroughly evaluate multiple factors to fully understand their role in OA, which needs further exploration and clarification.MethodsTwo-sample univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were employed to examine the causal effect of metabolic related factors on hip OA (HOA) or knee OA (KOA). The exposure and outcome datasets were obtained from Open GWAS IEU. All cases were independent European ancestry data. Three MR methods were performed to estimate the causal effect: inverse-variance weighting (IVW), weighted median method (WMM), and MR-Egger regression. Additionally, the intercept analysis in MR-Egger regression is used to estimate pleiotropy, and the IVW method and MR-Egger regression are used to test the heterogeneity.ResultsThe UVMR analysis revealed a causal relationship between FG and HOA. By MVMR analysis, the study discovered a significant link between FG (OR = 0.79, 95%CI: 0.64∼0.99, p = 0.036) and KOA after accounting for body mass index (BMI), age, and sex hormone-binding globulin (SHBG). However, no causal effects of FG on HOA were seen. Omega-3s and Omega-6s did not have a causal influence on HOA or KOA. No significant evidence of pleiotropy was identified.DiscussionThe MR investigation showed a protective effect of FG on KOA development but no causal relationship between FG and HOA. No causal effect of Omega-3s and Omega-6s on HOA and KOA was observed. Shared genetic overlaps might also exist between BMI and age, SHBG and PUFAs for OA development. This finding offers a novel insight into the treatment and prevention of KOA from glucose metabolism perspective. The FG cutoff value should be explored in the future, and consideration should be given to demonstrating the study in populations other than Europeans.