Abiotic synthesis of graphitic carbons in the Eoarchean Saglek-Hebron metasedimentary rocks.

Graphite in metasedimentary rocks of the Eoarchean Saglek-Hebron Gneiss Complex (Canada) is depleted in 13C and has been interpreted as one of the oldest traces of life on Earth. The variation in crystallinity of this oldest graphitic carbon could possibly confirm the effect of metamorphism on original biomass, but this is still unexplored. Here, we report specific mineral associations with graphitic carbons that also have a range of crystallinity in the Saglek-Hebron metasedimentary rocks. Petrographic, geochemical and spectroscopic analyses in the Saglek-Hebron banded iron formations suggest that poorly crystalline graphite is likely deposited from C-H-O fluids derived from thermal decomposition of syngenetic organic matter, which is preserved as crystalline graphite during prograde metamorphism. In comparison, in the Saglek-Hebron marble, disseminations of graphite co-occur with carbonate and magnetite disseminations, pointing to abiotic synthesis of graphitic carbons via decarbonation. Our results thus highlight that variably crystalline graphitic carbons in the Saglek-Hebron metasedimentary rocks are potential abiotic products on early Earth, which lay the groundwork for identifying the preservation of prebiotic organic matter through metamorphism on Earth and beyond.

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.

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.

Histamine H1 receptors in dentate gyrus-projecting cholinergic neurons of the medial septum suppress contextual fear retrieval in mice.

Fear memory is essential for survival and adaptation, yet excessive fear memories can lead to emotional disabilities and mental disorders. Despite previous researches have indicated that histamine H1 receptor (H1R) exerts critical and intricate effects on fear memory, the role of H1R is still not clarified. Here, we show that deletion of H1R gene in medial septum (MS) but not other cholinergic neurons selectively enhances contextual fear memory without affecting cued memory by differentially activating the dentate gyrus (DG) neurons in mice. H1R in cholinergic neurons mediates the contextual fear retrieval rather than consolidation by decreasing acetylcholine release pattern in DG. Furthermore, selective knockdown of H1R in the MS is sufficient to enhance contextual fear memory by manipulating the retrieval-induced neurons in DG. Our results suggest that H1R in MS cholinergic neurons is critical for contextual fear retrieval, and could be a potential therapeutic target for individuals with fear-related disorders.

Evaluation of fragility fracture risk using deep learning based on ultrasound radio frequency signal.

BACKGROUND: It was essential to identify individuals at high risk of fragility fracture and prevented them due to the significant morbidity, mortality, and economic burden associated with fragility fracture. The quantitative ultrasound (QUS) showed promise in assessing bone structure characteristics and determining the risk of fragility fracture. AIMS: To evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragility fractures retrospectively in postmenopausal women, and compared it with the traditional parameter of QUS, speed of sound (SOS), and bone mineral density (BMD) acquired with dual X-ray absorptiometry (DXA). METHODS: Using QUS, RF signal and SOS were acquired for 246 postmenopausal women. An MResNet was utilized, based on the RF signal, to categorize individuals with an elevated risk of fragility fracture. DXA was employed to obtain BMD at the lumbar, hip, and femoral neck. The fracture history of all adult subjects was gathered. Analyzing the odds ratios (OR) and the area under the receiver operator characteristic curves (AUC) was done to evaluate the effectiveness of various methods in discriminating fragility fracture. RESULTS: Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was competent to discriminate any fragility fracture (OR = 2.64; AUC = 0.74), Vertebral fracture (OR = 3.02; AUC = 0.77), and non-vertebral fracture (OR = 2.01; AUC = 0.69). After being modified by clinical covariates, the efficiency of MResNet was further improved to OR = 3.31-4.08, AUC = 0.81-0.83 among all fracture groups, which significantly surpassed QUS-SOS (OR = 1.32-1.36; AUC = 0.60) and DXA-BMD (OR = 1.23-2.94; AUC = 0.63-0.76). CONCLUSIONS: This pilot cross-sectional study demonstrates that the MResNet model based on the ultrasonic RF signal shows promising performance in discriminating fragility fractures in postmenopausal women. When incorporating clinical covariates, the efficiency of the modified MResNet is further enhanced, surpassing the performance of QUS-SOS and DXA-BMD in terms of OR and AUC. These findings highlight the potential of the MResNet as a promising approach for fracture risk assessment. Future research should focus on larger and more diverse populations to validate these results and explore its clinical applications.

In-Sensor Tactile Fusion and Logic for Accurate Intention Recognition.

Touch control intention recognition is an important direction for the future development of human-machine interactions (HMIs). However, the implementation of parallel-sensing functional modules generally requires a combination of different logical blocks and control circuits, which results in regional redundancy, redundant data, and low efficiency. Here, a location-and-pressure intelligent tactile sensor (LPI tactile sensor) unprecedentedly combined with sensing, computing, and logic is proposed, enabling efficient and ultrahigh-resolution action-intention interaction. The LPI tactile sensor eliminates the need for data transfer among the functional units through the core integration design of the layered structure. It actuates in-sensor perception through feature transmission, fusion, and differentiation, thereby revolutionizing the traditional von Neumann architecture. While greatly simplifying the data dimensionality, the LPI tactile sensor achieves outstanding resolution sensing in both location (<400 µm) and pressure (75 Pa). Synchronous feature fusion and decoding support the high-fidelity recognition of action and combinatorial logic intentions. Benefiting from location and pressure synergy, the LPI tactile sensor demonstrates robust privacy as an encrypted password device and interaction intelligence through pressure enhancement. It can recognize continuous touch actions in real time, map real intentions to target events, and promote accurate and efficient intention-driven HMIs.

Vat Photopolymerization of Ceramic Parts: Effects of Carbon Fiber Additives on Microstructure and Mechanical Performance.

Vat photopolymerization (VPP), as an additive manufacturing (AM) technology, can conveniently produce ceramic parts with high resolution and excellent surface quality. However, due to the inherent brittleness and low toughness of ceramic materials, manufacturing defect-free ceramic parts remains a challenge. Many researchers have attempted to use carbon fibers as additives to enhance the performance of ceramic parts, but these methods are mostly applied in processes like fused deposition modeling and hot pressing. To date, no one has applied them to VPP-based AM technology. This is mainly because the black carbon fibers reduce laser penetration, making it difficult to cure the ceramic slurry and thus challenging to produce qualified ceramic parts. To address this issue, our study has strictly controlled the amount of carbon fibers by incorporating trace amounts of carbon fiber powder into the original ceramic slurry with the aim to investigate the impact of these additions on the performance of ceramic parts. In this study, ceramic slurries with three different carbon fiber contents (0 wt.%, 0.1 wt.%, 0.2 wt.%, and 0.3 wt.%) were used for additive manufacturing. A detailed comparative analysis of the microstructure, physical properties, and mechanical performance of the parts was conducted. The experimental results indicate that the 3D-printed alumina parts with added carbon fibers show varying degrees of improvement in multiple performance parameters. Notably, the samples prepared with 0.2 wt.% carbon fiber content exhibited the most significant performance enhancements.

Improved assembly DC circuit breaker based on resonant current injection.

DC circuit breakers (DCCBs) with high breaking capacity and low cost are necessary for quick fault clearance in DC networks. The assembly DC circuit breakers (ADCCBs) have a main breaking section (MBS) and a sub-breaking sections (SBS) for each line, which greatly reduce the cost. But in conventional operation, it bears high voltage for a long time when there is a main switch grounding process in any line fault action. To address this problem, a multiport assembly circuit breaker based on current injection (CI-MPACB) is proposed, which is able to generate a resonant current with increasing amplitude by controlling the duty cycle of Integrated Gate-Commutated Thyristors (IGCTs). Then the resonant current is injected into the SBS to generate current zero crossing and arc extinction. A complex frequency domain circuit analysis is performed on the MBS to describe the action logic as well as the commutation characteristics. In addition, the parameters of each component of the MBS are subject to multiple constraints and reasonable design to ensure the fault current could be cut off quickly and reliably. The cost of existing design is greatly reduced due to the design idea of resonant current injection device parameter selection. Finally, a PSCAD/EMTDC simulation confirms the opening viability of CI-MPACB and the accuracy of the parameter design. The test results show that the designed CI-MPACB can cut off DC fault lines.

Comparative physiological, biochemical and transcriptomic analyses to reveal potential regulatory mechanisms in response to starvation stress in Cipangopaludina chinensis.

Cipangopaludina chinensis, as a financially significant species in China, represents a gastropod in nature which frequently encounters starvation stress owing to its limited prey options. However, the underlying response mechanisms to combat starvation have not been investigated in depth. We collected C. chinensis under several times of starvation stress (0, 7, 30, and 60 days) for nutrient, biochemical characteristics and transcriptome analyses. The results showed that prolonged starvation stress (> 30 days) caused obvious fluctuations in the nutrient composition of snails, with dramatic reductions in body weight, survival and digestive enzyme activity (amylase, protease, and lipase), and markedly enhanced the antioxidant enzyme activities of the snails. Comparative transcriptome analyses revealed 3538 differentially expressed genes (DEGs), which were significantly associated with specific starvation stress-responsive pathways, including oxidative phosphorylation and alanine, aspartate, and glutamate metabolism. Then, we identified 40 candidate genes (e.g., HACD2, Cp1, CYP1A2, and GPX1) response to starvation stress through STEM and WGCNA analyses. RT-qPCR verified the accuracy and reliability of the high-throughput sequencing results. This study provides insights into snail overwintering survival and the potential regulatory mechanisms of snail adaptation to starvation stress.

Revealing the Electro-oxidation Mechanism of 5-Aminotetrazole on Nickel-Based Oxides and Synthesizing 5,5'-Azotetrazolate Salts.

With the gradual expansion of the application of organic electromechanical synthesis in the field of energetic materials, it is necessary to explore deeply the mechanisms behind the organic electromechanical oxidation of energetic materials in order to develop efficient electrocatalysts. Electrochemical synthesis of 5,5'-azotetrazolate (ZT) salts is not only environmentally friendly and efficient but also can replace oxygen evolution reaction (OER) combined with hydrogen production, significantly reducing the battery voltage of overall water splitting (OWS) and achieving low energy consumption hydrogen production. Here, we prepared the Co-modified nickel-based oxide electrodes (Ni3-xCoO4/carbon cloth (CC), x = 1, 2) as a medium to reveal the oxidative coupling mechanism of 5-aminotetrazole (5-AT). Experimental and theoretical calculations verified that Ni-catalyzed oxidative coupling of 5-AT is a proton-coupled electron transfer (PCET) process, including electron transfer of electrocatalytic intermediates (Ni2+-O + OH- = Ni3+-O(OH) + e-) and spontaneous dehydrogenation process (Ni3+-O(OH) + X-H = Ni2+-O + X•). The Ni3+-O(OH) is an extremely fast nonreducing electron transfer center that serves as a chemical oxidant to directly abstract hydrogen atoms from the 5-AT. Simultaneously, the synergistic effect of Co doping on the electric cloud around Ni causes the upshift of the d-band centers, which is conducive to the easier adsorption of OH*, forming the generation of active intermediate Ni3+-O(OH). Thus, Ni2CoO4/CC has higher Faraday efficiency (FE) and yield for the oxidation reaction of 5-AT, with a yield of approximately 72.3% after electrolysis at 1.7 V vs reversible hydrogen electrode (RHE).

Antibacterial activity and mechanisms of D-3263 against Staphylococcus aureus.

Multi-drug-resistant Staphylococcus aureus infections necessitate novel antibiotic development. D-3263, a transient receptor potential melastatin member 8 (TRPM8) agonist, has potential antineoplastic properties. Here, we reported the antibacterial and antibiofilm activities of D-3263. Minimum inhibitory concentrations (MICs) against S. aureus, Enterococcus faecalis and E. faecium were ≤ 50 µM. D-3263 exhibited bactericidal effects against clinical methicillin-resistant S. aureus (MRSA) and E. faecalis strains at 4× MIC. Subinhibitory D-3263 concentrations effectively inhibited S. aureus and E. faecalis biofilms, with higher concentrations also clearing mature biofilms. Proteomic analysis revealed differential expression of 29 proteins under 1/2 × MIC D-3263, influencing amino acid biosynthesis and carbohydrate metabolism. Additionally, D-3263 enhanced membrane permeability of S. aureus and E. faecalis. Bacterial membrane phospholipids phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) dose-dependently increased D-3263 MICs. Overall, our data suggested that D-3263 exhibited potent antibacterial and antibiofilm activities against S. aureus by targeting the cell membrane.

Compact In Situ Electrochemical NMR with Wireless and Anti-interference Strategy in Multiscenario Applications.

The integration of electrochemistry with nuclear magnetic resonance (NMR) spectroscopy recently offers a powerful approach to understanding oxidative metabolism, detecting reactive intermediates, and predicting biological activities. This combination is particularly effective as electrochemical methods provide excellent mimics of metabolic processes, while NMR spectroscopy offers precise chemical analysis. NMR is already widely utilized in the quality control of pharmaceuticals, foods, and additives and in metabolomic studies. However, the introduction of additional and external connections into the magnet has posed challenges, leading to signal deterioration and limitations in routine measurements. Herein, we report an anti-interference compact in situ electrochemical NMR system (AICISENS). Through a wireless strategy, the compact design allows for the independent and stable operation of electrochemical NMR components with effective interference isolation. Thus, it opens an avenue toward easy integration into in situ platforms, applicable not only to laboratory settings but also to fieldwork. The operability, reliability, and versatility were validated with a series of biomimetic assessments, including measurements of microbial electrochemical systems, functional foods, and simulated drug metabolisms. The robust performance of AICISENS demonstrates its high potential as a powerful analytical tool across diverse applications.

Design and simulation investigations on charge transport layers-free in lead-free three absorber layer all-perovskite solar cells.

The multiple absorber layer perovskite solar cells (PSCs) with charge transport layers-free (CTLs-free) have drawn widespread research interest due to their simplified architecture and promising photoelectric characteristics. Under the circumstances, the novel design of CTLs-free inversion PSCs with stable and nontoxic three absorber layers (triple Cs3Bi2I9, single MASnI3, double Cs2TiBr6) as optical-harvester has been numerically simulated by utilizing wxAMPS simulation software and achieved high power conversion efficiency (PCE) of 14.8834%. This is owing to the innovative architecture of PSCs favors efficient transport and extraction of more holes and the slender band gap MASnI3 extends the absorption spectrum to the near-infrared periphery compared with the two absorber layers architecture of PSCs. Moreover, the performance of the device with p-type-Cs3Bi2I9/p-type-MASnI3/n-type-Cs2TiBr6 architecture is superior to the one with the p-type-Cs3Bi2I9/n-type-MASnI3/n-type-Cs2TiBr6 architecture due to less carrier recombination and higher carrier life time inside the absorber layers. The simulation results reveal that Cs2TiF6 double perovskite material stands out as the best alternative. Additionally, an excellent PCE of 21.4530% can be obtained with the thicker MASnI3 absorber layer thickness (0.4 µm). Lastly, the highest-performance photovoltaic devices (28.6193%) can be created with the optimized perovskite doping density of around E15 cm3 (Cs3Bi2I9), E18 cm3 (MASnI3), and 1.5E19 cm3 (Cs2TiBr6). This work manifests that the proposed CTLs-free PSCs with multi-absorber layers shall be a relevant reference for forward applications in electro-optical and optoelectronic devices.

Flexible Atg1/ULK complex composition activates selective autophagy for phosphate starvation.

The molecular basis for bulk autophagy activation due to a deficiency in essential nutrients such as carbohydrates, amino acids, and nitrogen is well understood. Given autophagy functions to reduce surplus to compensate for scarcity, it theoretically possesses the capability to selectively degrade specific substrates to meet distinct metabolic demands. However, direct evidence is still lacking that substantiates the idea that autophagy selectively targets specific substrates (known as selective autophagy) to address particular nutritional needs. Recently, Gross et al. found that during phosphate starvation (P-S), rather than nitrogen starvation (N-S), yeasts selectively eliminate peroxisomes by dynamically altering the composition of the Atg1/ULK kinase complex (AKC) to adapt to P-S. This study elucidates how the metabolite sensor Pho81 flexibly interacts with AKC and guides selective autophagic clearance of peroxisomes during P-S, providing novel insights into the metabolic contribution of autophagy to special nutritional needs.

Combining genome-wide association study and linkage mapping in the genetic dissection of amylose content in maize (Zea mays L.).

KEY MESSAGE: Integrated linkage and association analysis revealed genetic basis across multiple environments. The genes Zm00001d003102 and Zm00001d015905 were further verified to influence amylose content using gene-based association study. Maize kernel amylose is an important source of human food and industrial raw material. However, the genetic basis underlying maize amylose content is still obscure. Herein, we used an intermated B73 × Mo17 (IBM) Syn10 doubled haploid population composed of 222 lines and a germplasm set including 305 inbred lines to uncover the genetic control for amylose content under four environments. Linkage mapping detected 16 unique QTL, among which four were individually repeatedly identified across multiple environments. Genome-wide association study revealed 17 significant (P = 2.24E-06) single-nucleotide polymorphisms, of which two (SYN19568 and PZE-105090500) were located in the intervals of the mapped QTL (qAC2 and qAC5-3), respectively. According to the two population co-localized loci, 20 genes were confirmed as the candidate genes for amylose content. Gene-based association analysis indicated that the variants in Zm00001d003102 (Beta-16-galactosyltransferase GALT29A) and Zm00001d015905 (Sugar transporter 4a) affected amylose content across multi-environment. Tissue expression analysis showed that the two genes were specifically highly expressed in the ear and stem, respectively, suggesting that they might participate in sugar transport from source to sink organs. Our study provides valuable genetic information for breeding maize varieties with high amylose.

Patterns of neurogenic lower urinary tract dysfunction management and associated factors among Chinese community-dwelling individuals with spinal cord injury.

To identify different patterns of neurogenic lower urinary tract dysfunction management among Chinese community-dwelling individuals with spinal cord injury and explore the factors associated with latent classes. This was a cross-sectional study conducted in communities throughout China Mainland. Participants were recruited through the China Association of Persons with Physical Disability and a total of 2582 participants was included in the analysis. The data were collected by a questionnaire consisting of socio-demographic factors, disease-related factors, and a list of 8 bladder management methods. Latent class analysis was used to identify different latent classes of neurogenic lower urinary tract dysfunction management. Then the multinomial logistic regression was applied to analyze the relationship between neurogenic lower urinary tract dysfunction management patterns and socio-demographic and disease-related factors. Neurogenic lower urinary tract dysfunction management pattern among community-dwelling individuals with spinal cord injury was divided into four latent classes: "urinal collecting apparatus dominated pattern" (40.3%), "bladder compression dominated pattern" (30.7%), "intermittent catheterization dominated pattern" (19.3%) and "urethral indwelling catheterization dominated pattern" (9.6%). Multinomial logistic regression analysis found that the employment status, residential region, nursing need, payment method for catheterization products, hand function, time since spinal cord injury, urinary incontinence and concerns about social interaction affected by urination problems were significantly associated with latent classes. Only 19.3% of people used the intermittent catheterization as their main neurogenic lower urinary tract dysfunction management method. More attention needs to be paid to the promotion of the standardization process of intermittent catheterization in community-dwelling individuals with spinal cord injury. The associated factors of the four classes can be used for tailored and targeted interventions to increase the use of intermittent catheterization.

Investigation of optical polarization characteristics of ultraviolet-C AlGaN multiple quantum wells by angle-resolved cathodoluminescence.

AlGaN-based ultraviolet-C (UV-C) light-emitting diodes (LEDs) face challenges related to their extremely low external quantum efficiency, which is predominantly attributed to the remarkably inadequate transverse magnetic (TM) light extraction efficiency (LEE). In this study, we employ angle-resolved cathodoluminescence (ARCL) spectroscopy to assess the optical polarization of (0001)-oriented AlGaN multiple quantum well (MQW) structures in UV-C LEDs, in conjunction with a focused ion beam and scanning electron microscopy (FIB/SEM) system to etch samples with various inclination angles (θ) of sidewall. This technique effectively distinguishes the spatial distribution of TM- and transverse electric (TE)-polarized photons contributing to the luminescence of the MQW structure. CL spectroscopy confirms that UV-C LEDs with a θ of 35° exhibit the highest CL signal compared to samples with other θ. Furthermore, we establish a model using finite difference time domain (FDTD) simulation to validate the mechanism of the outcomes. The complementary contribution of TM and TE photons at different specific angles are distinguished by ARCL and confirmed by simulation. At angles near the sidewall, the CL is dominated by the TM photons, which mainly contribute to the increased LEE and the decreased degree of polarization (DOP) to make the spatial distribution of CL more uniform. Additionally, this method allows us to analyze the polarization of light without the need for polarizers, enabling the differentiation of TE and TM modes. This distinction provides flexibility for selecting different emission mode based on various application requirements. The presented approach not only opens up new opportunities for enhanced UV-C light extraction but also provides valuable insights for future endeavors in device fabrication and epitaxial film growth.

Enhancing the performance of AlGaN-based DUV-LEDs with multifocal laser stealth dicing.

In this study, AlGaN-based deep-ultraviolet light-emitting diodes (DUV-LEDs) processed via standard laser dicing (SLD) and multifocal laser stealth dicing (MFLSD) were investigated. Adopting the MFLSD technology would generate a roughing surface rather than the V-shaped grooves on the sidewall of 508 × 508 µm2 DUV-LEDs, which would reduce the forward operating voltage and increase the wall-plug efficiency, light output power, and far-field radiation patterns of these devices. In addition, the wavelength shift, far-field patterns, and light-tracing simulation results of the DUV-LEDs processed with SLD and MFLSD were clearly demonstrated and analyzed. Accordingly, it was observed that the MFLSD process provided more possibilities for photon escape to increase the light extraction efficiency (LEE) of DUV-LEDs, thus decreased the wavelength-redshift and junction temperature in DUV-LEDs. These results provide a reference for advanced nano-processing practices implemented during the fabrication of semiconductor devices.