Error-controlled adaptive machining of aeronautical cabin structures by laser triangulation on-machine measurement.

Laser Triangulation On-Machine Measurement (LTOMM) is being implemented increasingly to inspect aeronautical components accurately and efficiently, with its enhanced application in adaptive machining. This work proposes an error compensation and controlling method for measuring the typical features of steps, holes, and freeform surfaces to improve accuracy. Then, the global path to inspect the cabin's structures is planned by introducing optimization algorithms, thus providing an appropriate sequence to shorten the traveling length. After these, the test piece was designed, measured, and manufactured using the adaptive machining process that integrates the LTOMM. The results show that the measurement errors of steps, holes, and freeform surfaces are +0.0092, -0.006, and +0.0406 mm, respectively, and further reduced to +0.0013, -0.0019, and +0.0083 mm after error controlling. The cabin's freeform surface was fabricated with the maximum positive and minimum negative errors of +0.184 and -0.123 mm, which is evaluated by the mechanical probe. The measured data-driven machining process can guarantee that the error satisfies the required tolerance, promoting the application of the LTOMM process in aeronautical intelligent manufacturing.

Unravelling the novel sex determination genotype with 'ZY' and a distinctive 2.15-2.95 Mb inversion among poplar species through haplotype-resolved genome assembly and comparative genomics analysis.

Populus tomentosa, an indigenous tree species, is widely distributed and cultivated over 1,000,000 km2 in China, contributing significantly to forest production, ecological conservation and urban-rural greening. Although a reference genome is available for P. tomentosa, the intricate interspecific hybrid origins, chromosome structural variations (SVs) and sex determination mechanisms remain confusion and unclear due to its broad and even overlapping geographical distribution, extensive morphological variations and cross infiltration among white poplar species. We conducted a haplotype-resolved de novo assembly of P. tomentosa elite individual GM107, which comprises subgenomes a and b with a total genome size of 714.9 Mb. We then analysed the formation of hybrid species and the phylogenetic evolution and sex differentiation across the entire genus. Phylogenomic analyses suggested that GM107 likely originated from a hybridisation event between P. alba (♀) and P. davidiana (♂) approximately 3.8 Mya. A total of 1551 chromosome SVs were identified between the two subgenomes. More noteworthily, a distinctive inversion structure spanning 2.15-2.95 Mb was unveiled among Populus, Tacamahaca, Turaga, Aigeiros poplar species and Salix, highlighting a unique evolutionary feature. Intriguingly, a novel sex genotype of the ZY type, which represents a crossover between XY and ZW systems, was identified and confirmed through both natural and artificial hybrids populations. These novel insights offer significant theoretical value for the study of the species' evolutionary origins and serve as a valuable resource for ecological genetics and forest biotechnology.

Anlotinib potentiates anti-PD1 immunotherapy via transferrin receptor-dependent CD8+ T-cell infiltration in hepatocellular carcinoma.

BACKGROUND: The therapeutic potential of immune checkpoint blockade (ICB) extends across various cancers; however, its effectiveness in treating hepatocellular carcinoma (HCC) is frequently curtailed by both inherent and developed resistance. OBJECTIVE: This research explored the effectiveness of integrating anlotinib (a broad-spectrum tyrosine kinase inhibitor) with programmed death-1 (PD-1) blockade and offers mechanistic insights into more effective strategies for treating HCC. METHODS: Using patient-derived organotypic tissue spheroids and orthotopic HCC mouse models, we assessed the effectiveness of anlotinib combined with PD-1 blockade. The impact on the tumour immune microenvironment and underlying mechanisms were assessed using time-of-flight mass cytometry, RNA sequencing, and proteomics across cell lines, mouse models, and HCC patient samples. RESULTS: The combination of anlotinib with an anti-PD-1 antibody enhanced the immune response against HCC in preclinical models. Anlotinib remarkably suppressed the expression of transferrin receptor (TFRC) via the VEGFR2/AKT/HIF-1α signaling axis. CD8+ T-cell infiltration into the tumour microenvironment correlated with low expression of TFRC. Anlotinib additionally increased the levels of the chemokine CXCL14, crucial for attracting CD8+ T cells. CXCL14 emerged as a downstream effector of TFRC, exhibiting elevated expression following the silencing of TFRC. Importantly, low TFRC expression was also associated with a better prognosis, enhanced sensitivity to combination therapy, and a favourable response to anti-PD-1 therapy in patients with HCC. CONCLUSIONS: Our findings highlight anlotinib's potential to augment the efficacy of anti-PD-1 immunotherapy in HCC by targeting TFRC and enhancing CXCL14-mediated CD8+ T-cell infiltration. This study contributes to developing novel therapeutic strategies for HCC, emphasizing the role of precision medicine in oncology. HIGHLIGHTS: Synergistic effects of anlotinib and anti-PD-1 immunotherapy demonstrated in HCC preclinical models. Anlotinib inhibits TFRC expression via the VEGFR2/AKT/HIF-1α pathway. CXCL14 upregulation via TFRC suppression boosts CD8+ T-cell recruitment. TFRC emerges as a potential biomarker for evaluating prognosis and predicting response to anti-PD-1-based therapies in advanced HCC patients.

The role of BUD31 in clear cell renal cell carcinoma: prognostic significance, alternative splicing, and tumor immune environment.

BUD31, a splicing factor, is linked to various cancers. This study examines BUD31's expression, prognostic value, mutation profile, genomic instability, tumor immune environment, and role in clear cell renal cell carcinoma (ccRCC), focusing on cell cycle regulation via alternative splicing. BUD31 expression was analyzed using TCGA and GTEx databases across 33 cancers. Techniques included IHC staining, survival analysis, Cox regression, and nomogram construction. Mutation landscape, genomic instability, and tumor immune microenvironment were evaluated. Functional assays on ccRCC cell lines involved BUD31 knockdown, RNA sequencing, and alternative splicing analysis. BUD31 was upregulated in multiple tumors, including ccRCC. High BUD31 expression correlated with worse survival outcomes and was identified as an independent predictor of poor prognosis in ccRCC. High BUD31 expression also correlated with increased genomic instability and a less active immune microenvironment. BUD31 knockdown inhibited cell proliferation, migration, and invasion in vitro and reduced tumor growth in vivo. RNA sequencing identified 390 alternative splicing events regulated by BUD31, including 17 cell cycle-related genes. KEGG analysis highlighted pathways involved in cell cycle regulation, indicating BUD31's role in promoting cell cycle progression through alternative splicing. BUD31 is upregulated in various tumors and is associated with poor outcomes, increased genomic instability, and a suppressed immune microenvironment in ccRCC. BUD31 promotes cell cycle progression via alternative splicing, suggesting it as a prognostic biomarker and potential therapeutic target in ccRCC.

Chromosome-specific painting reveals the Y genome origin and chromosome rearrangements of the St genome in Triticeae.

Karyotypes provide key cytogenetic information on phylogenetic relationships and evolutionary origins in related plant species. The St genome of Pseudoroegneria contributes to eight alloploid genera, representing over half of the species that are highly valuable for wheat (Triticum aestivum) breeding and for understanding Triticeae species evolution. However, St chromosome characterization is challenging due to limited cytogenetic markers and DNA information. We developed a complete set of St genome-specific chromosome painting probes for identification of the individual chromosomes 1St to 7St based on the genome sequences of Pse. libanotica and wheat. We revealed the conservation of St chromosomes in St-containing species by chromosome painting, including Pseudoroegneria, Roegneria, Elymus, and Campeiostachys. Notably, the Y genome showed hybridization signals, albeit weaker than those of the St genome. The awnless species harboring the Y genome exhibited more intense hybridization signals compare to the awned species in Roegneria and Campeiostachys, yet weaker than the hybridization signals of the St genome in autotetraploid Pse. strigosa. Although awnless species were morphologically more similar to each other, phenotypic divergence progressively increased from awnless to awned species. Our results indicate that the Y genome originated from the St genome and shed light on the possible origin of the Roegneria and Campeiostachys species, enhancing our understanding of St-genome-containing species evolution.

Improved Nitrate-to-Ammonia Electrocatalysis through Hydrogen Poisoning Effects.

Electrochemical conversion from nitrate to ammonia is a key step in sustainable ammonia production. However, it suffers from low productive efficiency or high energy consumption due to a lack of desired electrocatalysts. Here we report nickel cobalt phosphide (NiCoP) catalysts for nitrate-to-ammonia electrocatalysis that display a record-high catalytic current density of -702±7 mA cm-2, ammonia production rate of 5415±26 mmol gcat-1 h-1 and Faraday efficiency of 99.7±0.2 % at -0.3 V vs. RHE, affording the estimated energy consumption as low as 22.7 kWh kgammonia-1. Theoretical and experimental results reveal that these catalysts benefit from hydrogen poisoning effects under low overpotentials, which leave behind catalytically inert adsorbed hydrogen species (HI*) at Co-hollow sites and thereupon enable ideally reactive HII* at secondary Co-P sites. The dimerization between HI* and HII* for H2 evolution is blocked due to the catalytic inertia of HI* thereby the HII* drives nitrate hydrogenation timely. With these catalysts, the continuous ammonia production is further shown in an electrolyser with a real energy consumption of 18.9 kWh kgammonia-1.

Incomplete histologic healing and diminished biomechanical strength of meniscus-bone interface after medial meniscus posterior root transosseous repair in a goat model.

PURPOSE: To enhance the understanding of histological healing after repairing medial meniscal posterior root tear (MMPRT) at an early stage, utilizing a goat model. METHODS: Eighteen adult goats, totaling thirty-six knee joints, were allocated into three groups (n = 12): Sham group (Sham), Root Tear group (RT), and Root Tear with Transosseous Suture group (RTS). At 12- and 24-week intervals post-surgery, all the knees were harvested for imaging, macroscopic, histological, and biomechanical assessments. RESULTS: The intact root served as a meniscus-bone interface which connected the tibial and the circular fibers of the meniscus, with a bony insertion and a root-meniscus transition. A direct-fibrous-connection displayed at the bony insertion proximal to the synovium in the RTS group, while the remaining regions of the root displayed indirect-fibrous healing. The healing in the RT group was disjointed and reminiscent of scar tissue. The RTS group exhibited a more pronounced coronal extrusion compared to the Sham group (0.42 ± 0.09 vs. 0.19 ± 0.02, P = 0.0012) but was improved relative to that of the RT group (0.49 ± 0.02, P = 0.0028). The failure load and stiffness of the RTS group were notably higher than those of the RT group, with a strength of 42.67% and a stiffness of 83.75% of the intact root. All the samples ruptured at the root-meniscus transitions. CONCLUSION: The incomplete healing may be attributed to the histological factors underlying the low healing rate and persistent MME. Notably, the region attached to the posterior-cruciate-ligament exhibited superior healing compared to other regions of the bony insertion in the repaired group. Conversely, the root-meniscus transition displayed discontinuity, representing a mechanical weakness in the healing process. CLINICAL RELEVANCE: Modifications of bone tunnel positioning and suture placement could be undertaken in subsequent studies to particularly enhance the healing of the root-meniscus transition.

Soil organic carbon formation efficiency from straw/stover and manure input and its drivers: Estimates from long-term data in global croplands.

New soil organic carbon (SOC) formation in cropland from straw/stover or manure input is a vital source of SOC for climate change mitigation. However, location and variations in the efficiency, specifically the ratio of new SOC formation to organic C input (NCE), remain unquantified globally. In this study, the spatial variability of cropland NCE from straw/stover or manure input and explanatory factors were determined by analyzing 897 pairs of long-term field measurements from 404 globally distributed sites and by mapping grid-level cropland NCEs. The global NCE for paddy and upland averaged 13.8% (8.7%-25.1%, 5th-95th percentile) and 10.9% (6.8%-17.3%), respectively. The initial SOC and the clay content of soil, rather than temperature, were the most important factors regulating NCE. A parabola with an apex at approximately 17 g kg-1 between the initial SOC and NCE was resolved, and a positive correlation between soil clay content and NCE was observed. High-resolution mapping of the global NCE derived from manure/straw and insight into NCE dynamics provide a benchmark for diagnosing cropland soil C dynamics under climate change and identifying priority regions and actions for C management.

Combining Fast Pure Shift NMR and GEMSTONE-Based Selective TOCSY for Efficient NMR Analysis of Complex Systems.

As one of the commonly used intact detection techniques, liquid NMR spectroscopy offers unparalleled insights into the chemical environments, structures, and dynamics of molecules. However, it generally encounters the challenges of crowded or even overlapped spectra, especially when probing complex sample systems containing numerous components and complicated molecular structures. Herein, we exploit a general NMR protocol for efficient NMR analysis of complex systems by combining fast pure shift NMR and GEMSTONE-based selective TOCSY. First, this protocol enables ultrahigh-selective observation on the coupling networks that are totally correlated with targeted resonances or components, even where they are situated in severely overlapped spectral regions. Second, pure shift simplification is introduced to enhance the spectral resolution and further resolve the subspectra containing spectral congestion, thus facilitating the dissection of overlapped spectra. Additionally, sparse sampling accompanied by spectral reconstruction is adopted to significantly accelerate acquisition and improve spectral quality. The advantages of this protocol were demonstrated on different complex sample systems, including a challenging compound of estradiol, a mixture of sucrose and d-glucose, and natural grape juice, verifying its feasibility and power, and boosting the potential application landscapes in various chemical fields.

Advances in understanding the graft healing mechanism: a review of factors and regulatory pathways.

Grafting is a widely used technique for asexual plant reproduction, especially in agriculture and forestry. This procedure is used to shorten the seedling period, improve the structure of scion branches, and help plants adapt to difficult environments. Although grafting has numerous benefits, several obstacles remain to be overcome. The connection between scion and rootstock is regulated by various factors, including phytohormones and molecular mechanisms, which are crucial for graft healing. This review provides an overview of recent advances in the field of grafting, with a specific focus on the factors and regulatory pathways that influence graft healing. The ultimate goal is to aid understanding of how to achieve successful grafting between plants and create desirable grafting chimeras. We provide an overview of the latest developments in plant grafting, covering aspects related to morphology, physiology, and molecular biology. We also discuss research directions in polyploid breeding and long-distance transfer of small molecules in grafted plants.

Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via Mitophagy-induced Apoptosis.

OBJECTIVE: Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. METHODS: Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. RESULTS: MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. CONCLUSION: Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

Sucrose Phosphate Synthase Genes in Plants: Its Role and Practice for Crop Improvement.

Plants convert solar energy and carbon dioxide into organic compounds through photosynthesis. Sucrose is the primary carbonate produced during photosynthesis. Sucrose phosphate synthase (SPS) is the key enzyme controlling sucrose biosynthesis in plants. There are at least three SPS gene families in higher plants, named A, B, and C. However, in monocotyledonous plants from Poaceae, there are at least five SPS gene families, named A, B, C, DIII, and DIV. Each family of SPS genes in different plants shows a divergent expression pattern. So different families of SPS genes participate in diverse biological functions, including sucrose accumulation, plant growth and production, and abiotic stress tolerance. SPS activity in plants is regulated by exogenous factors through gene expression and reversible protein phosphorylation. It is a practicable way to improve crop traits through SPS gene transformation. This work analyzes the cloning, phylogeny, and regulatory mechanism of the SPS gene in plants, reviews its biological function as well as its role in crop improvement, and discusses the challenges and future perspectives. This paper can serve as a reference for further study on plant SPS genes and eventually for crop improvement.

Tumor Cell Stemness and Stromal Cell Features Contribute to Oral Cancer Outcome Disparity in Black Americans.

Black Americans (BAs) with head and neck cancer (HNC) have worse survival outcomes compared to the White patients. While HNC disparities in patient outcomes for BAs have been well recognized, the specific drivers of the inferior outcomes remain poorly understood. Here, we investigated the biologic features of patient tumor specimens obtained during the surgical treatment of oral cancers and performed a follow-up study of the patients' post-surgery recurrences and metastases with the aim to explore whether tumor biologic features could be associated with the poorer outcomes among BA patients compared with White American (WA) patients. We examined the tumor stemness traits and stromal properties as well as the post-surgery recurrence and metastasis of oral cancers among BA and WA patients. It was found that high levels of tumor self-renewal, invasion, tumorigenesis, metastasis, and tumor-promoting stromal characteristics were linked to post-surgery recurrence and metastasis. There were more BA than WA patients demonstrating high stemness traits and strong tumor-promoting stromal features in association with post-surgery tumor recurrences and metastases, although the investigated cases displayed clinically comparable TNM stages and histological grades. These findings demonstrated that the differences in tumor stemness and stromal property among cancers with comparable clinical diagnoses contribute to the outcome disparity in HNCs. More research is needed to understand the genetic and molecular basis of the biologic characteristics underlying the inferior outcomes among BA patients, so that targeting strategies can be developed to reduce HNC disparity.

Experimental investigation of high-speed WDM-visible light communication using blue, green, and red InGaN µLEDs.

 Micro-light-emitting diodes (µLEDs) hold significant promise for applications in displays and visible light communication (VLC). This study substantiates the viability of a wavelength division multiplexing (WDM)-VLC system using InGaN blue, green, and red µLED devices. The devices exhibited notable color stability and high modulation bandwidth due to the weakly polarized electric field in the blue and green semipolar devices and the stress-optimized structure in the red device. The aggregated data rate reached 11.14 Gbps. Moreover, the blue, green, and red InGaN µLEDs exhibited a wide color gamut, encompassing 119.4% of the NTSC and 89.2% of the Rec. 2020 standards, affirming the potential of blue, green, and red InGaN µLEDs for applications in full-color display and WDM-VLC systems.

Enhancement of gemcitabine sensitivity in intrahepatic cholangiocarcinoma through Saikosaponin-a mediated modulation of the p-AKT/BCL-6/ABCA1 axis.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) remains a significant challenge in cancer therapy, especially due to its resistance to established treatments like Gemcitabine, necessitating novel therapeutic approaches. METHODS: This study utilized Gemcitabine-resistant cell lines, patient-derived organotypic tumor spheroids (PDOTs), and patient-derived xenografts (PDX) to evaluate the effects of Saikosaponin-a (SSA) on ICC cellular proliferation, migration, apoptosis, and its potential synergistic interaction with Gemcitabine. Techniques such as transcriptome sequencing, Luciferase reporter assays, and molecular docking were employed to unravel the molecular mechanisms. RESULTS: SSA exhibited antitumor effects in both in vitro and PDX models, indicating its considerable potential for ICC treatment. SSA markedly inhibited ICC progression by reducing cellular proliferation, enhancing apoptosis, and decreasing migration and invasion. Crucially, it augmented Gemcitabine's efficacy by targeting the p-AKT/BCL6/ABCA1 signaling pathway. This modulation led to the downregulation of p-AKT and suppression of BCL6 transcriptional activity, ultimately reducing ABCA1 expression and enhancing chemosensitivity to Gemcitabine. Additionally, ABCA1 was validated as a predictive biomarker for drug resistance, with a direct correlation between ABCA1 expression levels and the IC50 values of various small molecule drugs in ICC gene profiles. CONCLUSION: This study highlights the synergistic potential of SSA combined with Gemcitabine in enhancing therapeutic efficacy against ICC and identifies ABCA1 as a key biomarker for drug responsiveness. Furthermore, the introduction of the novel PDOTs microfluidic model provides enhanced insights into ICC research. This combination strategy may provide a novel approach to overcoming treatment challenges in ICC.

Formation mechanism of blue pigment in boiled lotus rhizome discs: Insight into the chelation of polyphenols and iron.

Boiled lotus rhizome discs (BLRDs), as common processed products of lotus rhizome, have gained increasing attention from consumers and food manufacturers. However, the blue pigment formed during boiling affects its appearance and reduces the appetite of BLRDs. In this study, the effects of polyphenols and iron contents on blue pigment formation in BLRDs in different regions and months were investigated. Results revealed that blue variation was more serious in March and April of the second year in Wuhan, and polyphenols and iron contents in these two months were significantly higher than those in other months. Then, UPLC and UV-Vis analysis showed that polyphenols causing the formation of blue pigment in BLRDs were L-dopa, gallocatechin, catechin, epigallocatechin, chlorogenic acid and epicatechin, among which L-dopa (52.450 mg/100 g in fresh lotus rhizome (FLR)) and gallocatechin (36.210 mg/100 g in FLR) possessed the greatest effect. Moreover, the ESI-Q-TOF-MS analysis of L-dopa-iron chelate and gallocatechin-iron chelate suggested that the blue pigment of BLRDs was mainly in the form of bis-complexes under boiling conditions. The study on formation mechanism of blue pigment in BLRDs can provide a reference for lotus rhizome processing.

Design and bio-evaluation of novel millepachine derivatives targeting tubulin colchicine binding site for treatment of osteosarcoma.

Microtubules are recognized as an appealing target for cancer treatment. We designed and synthesized of novel tubulin colchicine binding site inhibitors based on millepachine. Biological evaluation revealed compound 5h exhibited significant antiproliferative activity against osteosarcoma cell U2OS and MG-63. And compound 5h also remarkably inhibited tubulin polymerization. Further investigations indicated compound 5h not only arrest U2OS cells cycle at the G2/M phases, but also induced U2OS cells apoptosis in dose-dependent manners. Moreover, compound 5h was verified to inhibit cell migration and angiogenesis of HUVECs, induce mitochondrial membrane potential decreased and promoted the elevation of ROS levels. Furthermore, compound 5h exhibited remarkable effects on tumor growth in vivo, and the TGI rate was up to 84.94 % at a dose of 20 mg/kg without obvious toxicity. These results indicated that 5h may be an appealing tubulin inhibitor for treatment of osteosarcoma.

Discovery of a Highly Potent Lysine Methyltransferases G9a/NSD2 Dual Inhibitor to Treat Solid Tumors.

Both G9a and NSD2 have been recognized as promising therapeutic targets for cancer treatment. However, G9a inhibitors only showed moderate inhibitory activity against solid tumors and NSD2 inhibitors were limited to the treatment of hematological malignancies. Inspired by the advantages of dual-target inhibitors that show great potential in enhancing efficiency, we developed a series of highly potent G9a/NSD2 dual inhibitors to treat solid tumors. The candidate 16 demonstrated much enhanced antiproliferative activity compared to the selective G9a inhibitor 3 and NSD2 inhibitor 15. In addition, it exhibited superior potency in inhibiting colony formation, inducing cell apoptosis, and blocking cancer cell metastasis. Furthermore, it effectively inhibited the catalytic functions of both G9a and NSD2 in cells and exhibited significant antitumor efficacy in the PANC-1 xenograft model with good safety. Therefore, compound 16 as a highly potent G9a/NSD2 dual inhibitor presents an attractive anticancer drug candidate for the treatment of solid tumors.