Hinokione: an abietene diterpene with pancreatic ß cells regeneration and hypoglycemic activity, and other derivatives with novel structures from the woods of Agathis dammara.

In this study, 14 abietene and pimarene diterpenoids were isolated from the woods of Agathis dammara. Among them, 4 new compounds, dammarone A-C and dammaric acid A (1-4), were firstly reported, respectively. The structure of the new compounds was determined by HR ESI-MS and 1D/2D NMR spectroscopy, and their absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. The hypoglycemic effect of all compounds was evaluated by transgenic zebrafish model, and the structure-activity relationship was discussed. Hinokione (7, HO) has low toxicity and significant hypoglycemic effects on zebrafish, the mechanism is mainly by promoting the differentiation of zebrafish pancreatic endocrine precursor cells (PEP cells) into ß cells, thereby promoting the regeneration of pancreatic ß cells.

Metabolic landscape of head and neck squamous cell carcinoma informs a novel kynurenine/Siglec-15 axis in immune escape.

BACKGROUND: Metabolic reprograming and immune escape are two hallmarks of cancer. However, how metabolic disorders drive immune escape in head and neck squamous cell carcinoma (HNSCC) remains unclear. Therefore, the aim of the present study was to investigate the metabolic landscape of HNSCC and its mechanism of driving immune escape. METHODS: Analysis of paired tumor tissues and adjacent normal tissues from 69 HNSCC patients was performed using liquid/gas chromatography-mass spectrometry and RNA-sequencing. The tumor-promoting function of kynurenine (Kyn) was explored in vitro and in vivo. The downstream target of Kyn was investigated in CD8+ T cells. The regulation of CD8+ T cells was investigated after Siglec-15 overexpression in vivo. An engineering nanoparticle was established to deliver Siglec-15 small interfering RNA (siS15), and its association with immunotherapy response were investigated. The association between Siglec-15 and CD8+ programmed cell death 1 (PD-1)+ T cells was analyzed in a HNSCC patient cohort. RESULTS: A total of 178 metabolites showed significant dysregulation in HNSCC, including carbohydrates, lipids and lipid-like molecules, and amino acids. Among these, amino acid metabolism was the most significantly altered, especially Kyn, which promoted tumor proliferation and metastasis. In addition, most immune checkpoint molecules were upregulated in Kyn-high patients based on RNA-sequencing. Furthermore, tumor-derived Kyn was transferred into CD8+ T cells and induced T cell functional exhaustion, and blocking Kyn transporters restored its killing activity. Accroding to the results, mechanistically, Kyn transcriptionally regulated the expression of Siglec-15 via aryl hydrocarbon receptor (AhR), and overexpression of Siglec-15 promoted immune escape by suppressing T cell infiltration and activation. Targeting AhR in vivo reduced Kyn-mediated Siglec-15 expression and promoted intratumoral CD8+ T cell infiltration and killing capacity. Finally, a NH2-modified mesoporous silica nanoparticle was designed to deliver siS15, which restored CD8+ T cell function status and enhanced anti-PD-1 efficacy in tumor-bearing immunocompetent mice. Clinically, Siglec-15 was positively correlated with AhR expression and CD8+PD-1+ T cell infiltration in HNSCC tissues. CONCLUSIONS: The findings describe the metabolic landscape of HNSCC comprehensively and reveal that the Kyn/Siglec-15 axis may be a novel potential immunometabolism mechanism, providing a promising therapeutic strategy for cancers.

Effective Charge Collection of Electron Transport Layers for High-Performance Quantum Dot Infrared Solar Cells.

Infrared (IR) solar cells, capable of converting low-energy IR photons to electron-hole pairs, are promising optoelectronic devices by broadening the utilization range of the solar spectrum to the short-wavelength IR region. The emerging PbS colloidal quantum dot (QD) IR solar cells attract much attention due to their tunable band gaps in the IR region, potential multiple exciton generation, and facile solution processing. In PbS QD solar cells, ZnO is commonly utilized as an electron transport layer (ETL) to establish a depleted heterostructure with a QD photoactive layer. However, band gap shrinkage of large PbS QDs makes it necessary to tailor the behaviors of the ZnO ETL for efficient carrier extraction in the devices. Herein, the characteristics of ZnO ETL are efficiently and flexibly tailored to match the QD layer by handily adjusting the postannealing process of ZnO ETL. With a suitable temperature, the well-matched energy level alignment and suppressed trap states are simultaneously achieved in the ZnO ETL, effectively reducing the nonradiative recombination and accelerating the electron injection from the QD layer to ETL. As a consequence, a high-performance PbS QD photovoltaic device with power conversion efficiencies (PCEs) of 10.09% and 1.37% is obtained under AM 1.5 and 1100 nm filtered solar illumination, demonstrating a simple and effective approach for achieving high-performance IR photoelectric devices.

Transcriptomic profiling and risk assessment in bladder cancer: Insights from copper death-related genes.

BACKGROUND: The study aimed to investigate the role of copper death-related genes (CRGs) in bladder cancer (BC) for improved prognosis assessment. METHODS: Multi-omics techniques were utilized to analyze CRG expression in BC tissues from TCGA and GEO databases. Consensus clustering categorized patients into molecular subtypes based on clinical characteristics and immune cell infiltration. RESULTS: An innovative risk assessment model identified eight critical genes associated with patient risk. In vitro and in vivo experiments validated LIPT1's significant impact on copper-induced cell death, proliferation, migration, and invasion in BC. CONCLUSION: This multi-omics analysis elucidates the pivotal role of CRGs in BC progression, suggesting enhanced risk assessment through molecular subtype categorization and identification of key genes like LIPT1. Insights into these mechanisms offer the potential for improved diagnosis and treatment strategies for BC patients.

How perceived lack of benevolence harms trust of artificial intelligence management.

As organizations continue to supplement and replace human management with artificial intelligence (AI), it is essential that we understand the factors that influence employees' trust in AI management. Across one preregistered field study, where we survey 400 delivery riders in Mainland China, and three preregistered experiments (total N = 2,350), we find that AI management is perceived as less benevolent than human management. Given that benevolence is an important antecedent of trust in leaders, this perception has a negative effect on trust in AI management, even when controlling for perceived ability and integrity. Employees prefer human management to AI management in high empathy demand contexts, where individuals seek management that can empathize and experience the emotions that they are feeling, as opposed to low empathy demand contexts. These findings deepen our understanding of trust and provide important theoretical and practical insights on the implementation and adoption of AI management. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Design, Fabrication, and Characterization of a Planar Three-Electrode Trigger Switch Based on Flexible Printed Circuit Process.

An exploding foil initiator system (EFIs) is essential in modern weaponry for its safety and reliability. As the main component of EFIs, the performance of the switch is critical to EFIs. In this study, a planar three-electrode trigger switch was designed and fabricated using the Flexible Printed Circuits (FPC) process. Subsequently, the performance of the FPC switch was tested. The results show that the self-breakdown voltage of the FPC switch is stable. In addition, an FPF switch with a 0.6 mm main electrode gap demonstrated consistency, with delay times below 31.75 ns, and a jitter ranging from 1.7 ns to 10.94 ns at 900 V to 1200 V, evidencing the FPC switches' reliability and uniform performance across various voltages. Compared to the Micro-Electro-Mechanical Systems (MEMS) switches of similar dimensions, the FPC switches achieved a faster high-current attainment with less inductance, showing a 5% reduction in loop inductance. The repetitive testing results demonstrate that the FPC switch maintains consistent output performance, with stable peak currents, peak current time, and delay time over 50 action cycles, highlighting its repeatability. The FPC switch was assembled with an EFI chip and capacitor into an integrated system, which was subsequently able to successfully detonate HNS-IV at 1000 V/0.22 µF, proving the FPC switch's potential in low inductance applications.

A Micro Bridge-Wing-Thickened Low-Energy Exploding Foil Initiator Chip.

To enhance the energy efficiency of exploding foil initiator systems (EFIs) and mitigate energy loss due to ablation in the bridge-wing regions, a low-energy bridge-wing-thickened EFI chip was designed and fabricated. Computational analysis revealed that increasing the thickness of the bridge flanks significantly reduces ablation within the bridge region during the electrical explosion. The refinement of the design led to the adoption of a bridge flank thickness of 19 µm, with the bridge area dimensions specified as 0.25 mm × 0.25 mm × 4 µm. This bridge-wing-thickened EFI chip was produced by employing micro-electro-mechanical systems (MEMS) technology and underwent rigorous performance evaluations. The empirical results closely matched the computational predictions, thereby corroborating the precision of the proposed model in simulating the temperature distribution seen during the explosion process. Notably, this enhanced EFI design achieves a flyer velocity of 3800 m/s at a condition of 900 V/0.22 µF, signifying a significant advancement in EFI system efficiency and performance.

Development of an engineered Bacillus subtilis strain for antibiotic-free sucrose isomerase production.

Sucrose isomerase (SIase) catalyzes the hydrolysis and isomerization of sucrose into isomaltulose, a functional sugar extensively used in the food industry. However, the lack of safe and efficient heterologous expression systems for SIase has constrained its production and application. In this study, an engineered Bacillus subtilis strain for antibiotic-free SIase production was developed via a food-grade expression system. First, the B. subtilis strain TEA was modified through the CRISPR/Cas9 system, resulting in a mutant strain TEA4, which exhibited enhanced capabilities for recombinant protein expression. For efficient and safe production of SIase, different constitutive and inducible promoters were evaluated. The maltose-inducible promoter Poglv was found to have an extracellular SIase activity of 21.7 U mL-1 in engineered strain TEA4. Subsequent optimization of the culture medium further increased SIase activity to 26.4 U mL-1 during shake flask cultivation. Eventually, using the crude enzyme solution of the engineered strain in biotransformation reactions resulted in a high yield of isomaltulose under high concentrations sucrose, achieving a maximum yield of 83.1%. These findings demonstrated an engineered B. subtilis strain for antibiotic-free SIase production, paving the way for its scale-up industrial production and application.

Metabolomics of Vitis davidii Foëx. grapes from southern China: Flavonoids and volatiles reveal the flavor profiles of five spine grape varieties.

The spine grapes (Vitis davidii Foëx.) are wild grape species that grow in southern China, and can be used for table grapes, juicing and winemaking. To systematically investigate the flavor profiles of spine grapes, flavonoids and volatile compounds were detected in five spine grape varieties (Seputao, Ziqiu, Miputao, Tianputao and Baiputao) using HPLC-QqQ-MS/MS and GC-MS. The content of flavonoids highly depended on the variety, such as the total concentrations of anthocyanins (91.43-328.85 mg/kg FW) and flavonols (33.90 to 83.16 mg/kg FW). The volatile compounds with higher odor active value were selected to describe the aroma of spine grapes. Hexanal, (E)-2-hexenal and (E, Z)-2,6-nonadienal contributed to the higher herbaceous flavor to Baiputao and Ziqiu. ß-Damascenone and (E)-2-nonenal gave Baiputao a flavor with more floral, fruity and earthy. Their characteristic flavor compounds were subsequently revealed using multivariate statistical analysis. The results helped producers to further develop and utilize the spine grapes.

Chromosome-level genome assembly of Pedicularis kansuensis illuminates genome evolution of facultative parasitic plant.

Parasitic plants have a heterotrophic lifestyle, in which they withdraw all or part of their nutrients from their host through the haustorium. Despite the release of many draft genomes of parasitic plants, the genome evolution related to the parasitism feature of facultative parasites remains largely unknown. In this study, we present a high-quality chromosomal-level genome assembly for the facultative parasite Pedicularis kansuensis (Orobanchaceae), which invades both legume and grass host species in degraded grasslands on the Qinghai-Tibet Plateau. This species has the largest genome size compared with other parasitic species, and expansions of long terminal repeat retrotransposons accounting for 62.37% of the assembly greatly contributed to the genome size expansion of this species. A total of 42,782 genes were annotated, and the patterns of gene loss in P. kansuensis differed from other parasitic species. We also found many mobile mRNAs between P. kansuensis and one of its host species, but these mobile mRNAs could not compensate for the functional losses of missing genes in P. kansuensis. In addition, we identified nine horizontal gene transfer (HGT) events from rosids and monocots, as well as one single-gene duplication events from HGT genes, which differ distinctly from that of other parasitic species. Furthermore, we found evidence for HGT through transferring genomic fragments from phylogenetically remote host species. Taken together, these findings provide genomic insights into the evolution of facultative parasites and broaden our understanding of the diversified genome evolution in parasitic plants and the molecular mechanisms of plant parasitism.

Bioinformatics and Functional Analysis of OsASMT1 Gene in Response to Abiotic Stress.

The study aimed to elucidate the functional characteristics of OsASMT1 gene under copper (Cu) or sodium chloride (NaCl) stress. Bioinformatics scrutiny unveiled that OsASMT1 is situated on chromosome 9. Its protein architecture, comprising dimerization and methyltransferase domains, showed significant similarities to OsASMT2 and OsASMT3. High expression in roots and panicles, along with abiotic stress putative cis-regulatory elements in the promoter, indicated potential stress responsiveness. Real-time quantitative PCR confirmed OsASMT1 induction under Cu and NaCl stress in rice. Surprisingly, yeast expressing OsASMT1 did not exhibit enhanced resistance to abiotic stresses. The results of subcellular localization analysis indicated that OsASMT1 plays a role in the cytoplasm. While OsASMT1 responded to Cu and NaCl stress in rice, its heterologous expression in yeast failed to confer abiotic stress resistance, highlighting the need for further investigation of its functional implications.

Online Detection of Laser Welding Penetration Depth Based on Multi-Sensor Features.

The accurate online detection of laser welding penetration depth has been a critical problem to which the industry has paid the most attention. Aiming at the laser welding process of TC4 titanium alloy, a multi-sensor monitoring system that obtained the keyhole/molten pool images and laser-induced plasma spectrum was built. The influences of laser power on the keyhole/molten pool morphologies and plasma thermo-mechanical characteristics were investigated. The results showed that there were significant correlations among the variations of the keyhole-molten pool, plasma spectrum, and penetration depth. The image features and spectral features were extracted by image processing and dimension-reduction methods, respectively. Moreover, several penetration depth prediction models based on single-sensor features and multi-sensor features were established. The mean square error of the neural network model built by multi-sensor features was 0.0162, which was smaller than that of the model built by single-sensor features. The established high-precision model provided a theoretical basis for real-time feedback control of the penetration depth in the laser welding process.

Unique Advantages of Dendrimers-Structured Mesoporous Silica Nanoparticles over Traditional Hollow Ones in Delivering Bcl2-Functional Converting Peptide for Multidrug Resistant Cancer Treatment.

Innovative silica nanomaterials have made the significant advancements in curative therapy against cancers with multidrug resistance (MDR). The study on different-nanostructured mesoporous silica nanoparticles (MSNs) with discrepant pore sizes affecting biomacromolecules in resisting cancer MDR hasn't been reported yet. In this study, a systematic comparison of 6 nm-pore sized hollow-structured MSNs (HMSNs) and 10 nm-pore sized dendrimers-structured MSNs (LMSNs) for delivering Bcl-2-functional converting peptide (N9) or doxorubicin (DOX) to overcome cancer MDR is comprehensively carried out both in in vitro and in vivo resistant tumor models. The results show that both LMSNs and HMSNs exert no significant difference in delivering DOX to treat drug-resistant cancers. However, compared with N9@HMSNs, N9@LMSNs display the increased loading efficiency, the improved cell-penetrative capability, the higher cancer cell apoptosis effect, the enhanced tumor accumulation and retention efficiency, and the final elevated tumor inhibition efficiency. Unexpectedly, naked LMSNs without surface modification especially at high dosage produce relatively more serious toxicity than HMSNs whatever in cells, zebrafish embryo or mice models. Collectively, the data provide the sufficient theoretical evidence that LMSNs might be a better choice for delivering biomacromolecules to treat resistant cancers after appropriate surface functionalization such as with PEGylation to weaken its intrinsic toxicity.

π-π Stacking at the Perovskite/C60 Interface Enables High-Efficiency Wide-Bandgap Perovskite Solar Cells.

Interface passivation is a key method for improving the efficiency of perovskite solar cells, and 2D/3D perovskite heterojunction is the mainstream passivation strategy. However, the passivation layer also produces a new interface between 2D perovskite and fullerene (C60), and the properties of this interface have received little attention before. Here, the underlying properties of the 2D perovskite/C60 interface by taking the 2D TEA2PbX4 (TEA = C6H10NS; X = I, Br, Cl) passivator as an example are systematically expounded. It is found that the 2D perovskite preferentially exhibits (002) orientation with the outermost surface featuring an oriented arrangement of TEACl, where the thiophene groups face outward. The outward thiophene groups further form a strong π-π stacking system with C60 molecule, strengthening the interaction force with C60 and facilitating the creation of a superior interface. Based on the vacuum-assisted blade coating, wide-bandgap (WBG, 1.77 eV) perovskite solar cells achieved impressive records of 19.28% (0.09 cm2) and 18.08% (1.0 cm2) inefficiency, respectively. This research not only provides a new understanding of interface processing for future perovskite solar cells but also lays a solid foundation for realizing efficient large-area devices.

Study on the Effect of Nanoporous Copper Particle Size on Copper-Based Azide.

Preparing copper-based azide by in situ reaction is well-suited for MEMS processing technology and holds promising prospects in the field of MEMS micro-initiators. This study involved the preparation of porous copper with particle sizes of approximately 30 nm, 60 nm and 100 nm through powder sintering. These were used as precursors for a gas-solid in situ azide reaction to produce copper-based azide with varying morphologies and compositions. Copper-based azide micro-initiators were designed, and their output performance was evaluated using CL-20 and HNS-IV explosives. Analytical results revealed that the product from the reaction of the 100 nm precursor exhibited a lumpy and uneven structure with a conversion rate of 90.36%. The product from the 60 nm precursor reaction had a dense surface with a conversion rate of 94.56%, while the 30 nm precursor resulted in a needle-like form with a conversion rate of 92.82%. Detonation experiments demonstrated that the copper-based azide micro-initiators prepared with 100 nm of a porous copper precursor exhibited unstable output performance, requiring a 1.6 mg charge to successfully detonate CL-20 explosives. On the other hand, copper-based azide micro-initiators prepared from 60 nm and 30 nm of porous copper precursors exhibited stable output performance. A charge of 0.8 mg was adequate for reliably and consistently detonating CL-20 and HNS-IV explosives. The reduced particle size of the precursor enhanced the output performance of the copper-based azide micro-initiators, providing increased energy redundancy during detonation and improving overall usage reliability.

Fine Optimization of Colloidal Photonic Crystal Structural Color for Physically Unclonable Multiplex Encryption and Anti-Counterfeiting.

Robust anti-counterfeiting techniques aim for easy identification while remaining difficult to forge, especially for high-value items such as currency and passports. However, many existing anti-counterfeiting techniques rely on deterministic processes, resulting in loopholes for duplication and counterfeiting. Therefore, achieving high-level encryption and easy authentication through conventional anti-counterfeiting techniques has remained a significant challenge. To address this, this work proposes a solution that combined fluorescence and structural colors, creating a physically unclonable multiplex encryption system (PUMES). In this study, the physicochemical properties of colloidal photonic inks are systematically adjusted to construct a comprehensive printing phase diagram, revealing the printable region. Furthermore, the brightness and color saturation of inkjet-printed colloidal photonic crystal structural colors are optimized by controlling the substrate's hydrophobicity, printed droplet volume, and the addition of noble metals. Finally, fluorescence is incorporated to build PUMES, including macroscopic fluorescence and structural color patterns, as well as microscopic physically unclonable fluorescence patterns. The PUMES with intrinsic randomness and high encoding capacity are authenticated by a deep learning algorithm, which proved to be reliable and efficient under various observation conditions. This approach can provide easy identification and formidable resistance against counterfeiting, making it highly promising for the next-generation anti-counterfeiting of currency and passports.

Synthesis and Antimicrobial Activity Evaluation of Pyridine Derivatives Containing Imidazo[2,1-b][1,3,4]Thiadiazole Moiety.

Four series of novel pyridine derivatives (17 a-i, 18 a-i, 19 a-e, and 20 a-e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target compounds showed moderate or high antibacterial activity. The 4-F substituted compound 17 d (MIC=0.5 µg/mL) showed the highest antibacterial activity, its activity was twice the positive control compound gatifloxacin (MIC=1.0 µg/mL). For fungus ATCC 9763, the activities of compounds 17 a and 17 d are equivalent to the positive control compound fluconazole (MIC=8 µg/mL). Furthermore, compounds 17 a and 17 d showed little cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra-high concentration (200 µM). The results indicate that these compounds are valuable for further development as antibacterial and antifungal agents.

Simultaneous determination of advanced glycation end products and heterocyclic amines in roast/grilled meat by UPLC-MS/MS.

Advanced glycation end products (AGEs) and heterocyclic amines (HAs) are main harmful Maillard reaction products of meat products. Simultaneous quantification of both with high sensitivity, selectivity and accuracy remains a major challenge due to inconsistencies in their pre-treatment and instrumental methods and the different polarity of AGEs and HAs. We developed a method for the simultaneous determination of AGEs and HAs in roast/grilled meat by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) using dynamic multiple reaction monitoring (D-MRM). The instrument parameters and pre-treatment method were optimized to achieve reasonably good separation and high response for the 11 target analytes within 8 min. From 10 to 200 ng/mL, the limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.3 to 5.5 µg/L and 0.9 to 6.3 µg/L, respectively, and the correlation coefficient (R2) was >0.99. It was acceptable to recoveries, standard deviations (RSDs), and matrix effects. Six types of roast/grilled meat samples were then tested using the developed method.

A Study of Electroplated Nanoporous Copper Using Aberration-Corrected Transmission Electron Microscopy.

Nanoporous Cu foam is widely applied in many fields such as the packaging of electronic power devices. In this study, a sandwich-structured Cu-Zn eutectic alloy precursor composed of Cu0.53Zn0.47/Cu5Zn8/Cu0.53Zn0.47 is prepared through electroplating. The surface layer of the precursor, Cu0.53Zn0.47, has a flat surface with numerous grain boundaries, which effectively promotes its dealloying behavior. By contrast, Cu5Zn8 has a porous structure, which promotes the dealloying behavior at the center of the precursor. The dealloying of Cu0.53Zn0.47 is dominated by the coherent surface diffusion of Cu atoms, and the crystal lattice and orientation show no changes before and after dealloying. By contrast, the dealloying behavior of Cu5Zn8 requires the renucleation of Cu crystals; in this process, Cu atoms are transported to the surface of the layer by capillary forces to form clusters, which nucleate and grow.

Study on the Relationship between Particulate Methane Monooxygenase and Methanobactin on Gold-Nanoparticles-Modified Electrodes.

(1) Background: Particulate methane monooxygenase (pMMO) has a strong dependence on the natural electron transfer path and is prone to denaturation, which results in its redox activity centers being unable to transfer electrons with bare electrodes directly and making it challenging to observe an electrochemical response; (2) Methods: Using methanobactin (Mb) as the electron transporter between gold electrodes and pMMO, a bionic interface with high biocompatibility and stability was created. The Mb-AuNPs-modified functionalized gold net electrode as a working electrode, the kinetic behaviors of pMMO bioelectrocatalysis, and the effect of Mb on pMMO were analyzed. The CV tests were performed at different scanning rates to obtain electrochemical kinetics parameters. (3) Results: The values of the electron transfer coefficient (α) and electron transfer rate constant (ks) are relatively large in test environments containing only CH4 or O2. In contrast, in the test environment containing both CH4 and O2, the bioelectrocatalysis of pMMO is a two-electron transfer process with a relatively small α and ks; (4) Conclusions: It was inferred that Mb formed the complex with pMMO. More importantly, Mb not only played a role in electron transfer but also in stabilizing the enzyme structure of pMMO and maintaining a specific redox state. Furthermore, the continuous catalytic oxidation of natural substrate methane was realized.