Copper regulates the host innate immune response against bacterial infection via activation of ALPK1 kinase.

Copper is an essential trace element for the human body, and its requirement for optimistic immune functions has been recognized for decades. How copper is involved in the innate immune pathway, however, remains to be clarified. Here, we report that copper serves as a signal molecule to regulate the kinase activity of alpha-kinase 1 (ALPK1), a cytosolic pattern-recognition receptor (PRR), and therefore promotes host cell defense against bacterial infection. We show that in response to infection, host cells actively accumulate copper in the cytosol, and the accumulated cytosolic copper enhances host cell defense against evading pathogens, including intracellular and, unexpectedly, extracellular bacteria. Subsequently, we demonstrate that copper activates the innate immune pathway of host cells in an ALPK1-dependent manner. Further mechanistic studies reveal that copper binds to ALPK1 directly and is essential for the kinase activity of this cytosolic PRR. Moreover, the binding of copper to ALPK1 enhances the sensitivity of ALPK1 to the bacterial metabolite ADP-heptose and eventually prompts host cells to elicit an enhanced immune response during bacterial infection. Finally, using a zebrafish in vivo model, we show that a copper-treated host shows an increased production of proinflammatory cytokines, enhanced recruitment of phagosome cells, and promoted bacterial clearance. Our findings uncover a previously unrecognized role of copper in the modulation of host innate immune response against bacterial pathogens and advance our knowledge on the cross talk between cytosolic copper homeostasis and immune system.

Altered modes of stem cell division drive adaptive intestinal growth.

Throughout life, adult organs continually adapt to variable environmental factors. Adaptive mechanisms must fundamentally differ from homeostatic maintenance, but little is known about how physiological factors elicit tissue remodeling. Here, we show that specialized stem cell responses underlie the adaptive resizing of a mature organ. In the adult Drosophila midgut, intestinal stem cells interpret a nutrient cue to "break homeostasis" and drive growth when food is abundant. Activated in part by niche production of insulin, stem cells direct a growth program through two altered modes of behavior: accelerated division rates and predominance of symmetric division fates. Together, these altered modes produce a net increase in total intestinal cells, which is reversed upon withdrawal of food. Thus, tissue renewal programs are not committed to maintain cellular equilibrium; stem cells can remodel organs in response to physiological triggers.

Multifunctional integrated metamaterials for radar-infrared-visible compatible multispectral stealth.

Metamaterials offer exciting opportunities for developing multispectral stealth due to their unique electromagnetic properties. However, currently transparent radar-infrared-visible compatible stealth metamaterials typically involve complex hierarchical designs, leading to thickness and transparency limitations. Here, we propose an integrated metamaterial for multispectral stealth with high transparency. Our design features an ITO/dielectric/ITO sandwich structure, with the upper-layer ITO acting as a resonator for broadband microwave absorption while maintaining a high filling ratio to suppress infrared (IR) radiation. Experimental results demonstrate excellent performance, with over 90% microwave absorption in 8-18 GHz, an IR emissivity of approximately 0.36 in 3-14 µm, an average optical transmittance of 74.1% in 380-800 nm, and a thickness of only 2.4 mm. With its multispectral compatibility, the proposed metamaterial has potential applications in stealth and camouflage fields.

Synergistic Engineering of Energy Band Alignment and Interfacial Electric Field Distribution over Bi-bismuth-Based Hetero-nanofibers for Boosting Visible-Light-Driven Photocatalytic Ammonia Synthesis and Antibiotic Removal.

Synergistic engineering of energy band alignment and interfacial electric field distribution is essential for photocatalyst design but is still challenging because of the limitation on refined regulation in the nanoscale. This study addresses the issue by employing surface modification and thermal-induced phase transformation in Bi2MoO6/BixOyIz hetero-nanofiber frameworks. The energy band alignment switches from a type-II interface to a Z-scheme contact with stronger redox potentials and inhibited electron traps, and the optimized built-in electric field distribution could be reached based on experimental and theoretical investigations. The engineered hetero-nanofibers exhibit outstanding visible-light-driven photocatalytic nitrogen reduction activity (605 µmol/g/h) and tetracycline hydrochloride removal rate (81.5% within 30 min), ranking them among the top-performing bismuth series materials. Furthermore, the photocatalysts show promise in activating advanced oxidants for efficient organic pollutant degradation. Moreover, the Bi2MoO6/Bi5O7I hetero-nanofibers possess good recycling stability owing to their three-dimensional network structure. This research offers valuable insights into heterojunction design for environmental remediation and industrial applications.

Carboxylic Acid-Enabled Vinylene Transfer Reaction by Co(III) Catalyst: Scope and Applications to the Five-Step Total Synthesis of Protoberberine Alkaloids Containing Free Hydroxyl Group without Protection.

A Co(III)-catalyzed vinylene transfer reaction enabled by carboxylic acid is presented. This redox-neutral transformation tolerates various functional groups, including free hydroxyl groups, and features practicality. Five-step routes based on the vinylene transfer reaction and Heck annulation have been devised to the total synthesis of 8-oxodehydrodiscretamine and 2-demethyl-oxypalmatine without the protection of the free hydroxyl functionality.

The long ß2,3-sheets encoded by redundant sequences play an integral role in the channel function of P2X7 receptors.

P2X receptors are a class of nonselective cation channels widely distributed in the immune and nervous systems, and their dysfunction is a significant cause of tumors, inflammation, leukemia, and immune diseases. P2X7 is a unique member of the P2X receptor family with many properties that differ from other subtypes in terms of primary sequence, the architecture of N- and C-terminals, and channel function. Here, we suggest that the observed lengthened ß2- and ß3-sheets and their linker (loop ß2,3), encoded by redundant sequences, play an indispensable role in the activation of the P2X7 receptor. We show that deletion of this longer structural element leads to the loss of P2X7 function. Furthermore, by combining mutagenesis, chimera construction, surface expression, and protein stability analysis, we found that the deletion of the longer ß2,3-loop affects P2X7 surface expression but, more importantly, that this loop affects channel gating of P2X7. We propose that the longer ß2,3-sheets may have a negative regulatory effect on a loop on the head domain and on the structural element formed by E171 and its surrounding regions. Understanding the role of the unique structure of the P2X7 receptor in the gating process will aid in the development of selective drugs targeting this subtype.

DNA methylome and transcriptome identified Key genes and pathways involved in Speckled Eggshell formation in aged laying hens.

BACKGROUND: The quality of poultry eggshells is closely related to the profitability of egg production. Eggshell speckles reflect an important quality trait that influences egg appearance and customer preference. However, the mechanism of speckle formation remains poorly understood. In this study, we systematically compared serum immune and antioxidant indices of hens laying speckled and normal eggs. Transcriptome and methylome analyses were used to elucidate the mechanism of eggshell speckle formation. RESULTS: The results showed that seven differentially expressed genes (DEGs) were identified between the normal and speckle groups. Gene set enrichment analysis (GSEA) revealed that the expressed genes were mainly enriched in the calcium signaling pathway, focal adhesion, and MAPK signaling pathway. Additionally, 282 differentially methylated genes (DMGs) were detected, of which 15 genes were associated with aging, including ARNTL, CAV1, and GCLC. Pathway analysis showed that the DMGs were associated with T cell-mediated immunity, response to oxidative stress, and cellular response to DNA damage stimulus. Integrative analysis of transcriptome and DNA methylation data identified BFSP2 as the only overlapping gene, which was expressed at low levels and hypomethylated in the speckle group. CONCLUSIONS: Overall, these results indicate that aging- and immune-related genes and pathways play a crucial role in the formation of speckled eggshells, providing useful information for improving eggshell quality.

Genome-wide association study exploring the genetic architecture of eggshell speckles in laying hens.

BACKGROUND: Eggshell speckle phenotype is an important trait in poultry production because they affect eggshell quality. However, the genetic architecture of speckled eggshells remains unclear. In this study, we determined the heritability of eggshell speckles and conducted a genome-wide association study (GWAS) on purebred Rhode Island Red (RIR) hens at 28 weeks to detect potential genomic loci and candidate genes associated with eggshell speckles. RESULTS: The heritability of eggshell speckles was 0.35 at 28 weeks, and the speckle level is not related to other eggshell quality traits in terms of phenotypic correlation. We detected 311 SNPs (6 significantly, and 305 suggestively associated) and 39 candidate genes associated with eggshell speckles. Based on the pathway analysis, the 39 candidate genes were mainly involved in alpha-linolenic acid metabolism, linoleic acid metabolism, ether lipid metabolism, GnRH signaling pathway, vascular smooth muscle contraction, and MAPK signaling pathway. Ultimately, ten genes, LOC423226, SPTBN5, EHD4, LOC77155, TYRO3, ITPKA, DLL4, PLA2G4B, PLA2G4EL5, and PLA2G4EL6 were considered the most promising genes associated with eggshell speckles that were implicated in immunoregulation, calcium transport, and phospholipid metabolism, while its function in laying hens requires further studies. CONCLUSIONS: This study provides new insights into understanding the genetic basis of eggshell speckles and has practical application value for the genetic improvement of eggshell quality.

Reduced Adenoma Miss Rate With 9-Minute vs 6-Minute Withdrawal Times for Screening Colonoscopy: A Multicenter Randomized Tandem Trial.

INTRODUCTION: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR. METHODS: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367). The primary outcome was the lesion-level AMR. RESULTS: The intention-to-treat analysis revealed that 9MF significantly reduced the lesion-level (14.5% vs 36.6%, P < 0.001) and participant-level AMR (10.9% vs 25.9%, P < 0.001), advanced adenoma miss rate (AAMR, 5.3% vs 46.9%, P = 0.002), multiple adenomas miss rate (20.7% vs 56.5%, P = 0.01), and high-risk adenomas miss rate (14.6% vs 39.5%, P = 0.01) of 6MF without compromising detection efficiency ( P = 0.79). In addition, a lower false-negative rate for adenomas ( P = 0.002) and high-risk adenomas ( P < 0.05), and a lower rate of shortening surveillance schedule ( P < 0.001) were also found in 9MF, accompanying with an improved ADR in the 9-minute vs 6-minute m-WT (42.3% vs 33.5%, P = 0.02). The independent inverse association between m-WT and AMR remained significant even after adjusting ADR, and meanwhile, 9-minute m-WT was identified as an independent protector for AMR and AAMR. DISCUSSION: In addition to increasing ADR, 9-minute m-WT also significantly reduces the AMR and AAMR of screening colonoscopy without compromising detection efficiency.

Dynamic Changes of Composition of Particulate Matter Emissions during Residential Biomass Combustion.

Residential biomass combustion in developing countries produces significant primary particulate matter (PM) emissions. Highly time-resolved aerosol mass spectrometry and aethalometer measurements were used to investigate the dynamic changes of emitted PM chemical composition from a typical improved stove burning with wood and crop straw in China. Combustion temperature and organic aerosol (OA) concentration increased quickly during the ignition stage. The flaming stage was characterized by high combustion temperature and high pollutant [including OA, black carbon (BC), inorganic salts, and polycyclic aromatic hydrocarbons (PAHs)] emissions, while the burnout stage is characterized by low combustion temperature and lower pollutant emissions. OA was the primary emitted species; emission factors of OA in the flaming stage were generally higher (24.5-792%) than those in the burnout stage. Mass spectral signatures of OA were obtained. The ratio of Cl-/OA for wood combustion (0.05 ± 0.01) is much lower than that from burning crop straw (0.32 ± 0.19). Hydrocarbon OA emissions dominated during the ignition and flaming stages. A high percentage of oxidized OA was emitted during the burnout stage. The relationship between PAHs and BC/OA emissions under different burning conditions was investigated, and PAHs may act as intermediate products in the conversion of OA to BC.

Pulse-shaped high-energy and high-average-power fiber laser in the nanosecond regime.

A high-energy and high-average-power pulsed fiber laser has been investigated in a master oscillator power amplifier (MOPA) configuration seeding with a diode laser at a programmed pulse duration of ∼250ns. The fiber amplifier successfully demonstrates the pulse with 21.4 mJ at the repetition rate of 50 kHz and a maximum average output power of 1535 W with a slope efficiency of 81.6% at 250 kHz. To overcome fiber nonlinearities such as stimulated Raman scattering (SRS) and self-phase modulation (SPM), extra-large mode area ytterbium (Yb)-doped step-index dual cladding fiber has been utilized as gain fiber in the MOPA laser system. The gain saturation effect in the power amplifier was greatly mitigated by the programmed seed signal. This pulse-shaped MOPA system can provide practical applications in many fields such as laser cleaning, paint stripping, and other applications requiring special pulse shapes.

Genomic and transcriptomic analyses reveal genetic adaptation to cold conditions in the chickens.

Under the pressure of natural and artificial selection, domestic animals, including chickens, have evolved unique mechanisms of genetic adaptations such as high-altitude adaptation, hot and arid climate adaptation, and desert adaptation. Here, we investigated the genetic basis of cold tolerance in chicken by integrating whole-genome and transcriptome sequencing technologies. Genome-wide comparative analyses of 118 chickens living in different latitudes showed 46 genes and several pathways that may be involved in cold adaptation. The results of the functional enrichment analysis of differentially expressed genes proved the important role of metabolic pathways and immune-related pathways in cold tolerance in chickens. The subsequent integration of whole genome and transcriptome sequencing technology further identified six genes - dnah5 (dynein axonemal heavy chain 5), ptgs2 (prostaglandin-endoperoxide synthase 2), inhba (inhibin beta A subunit), irx2 (iroquois homeobox 2), ensgalg00000054917, and ensgalg00000046652 - requiring more detailed studies. In addition, we also discovered different allele frequency distributions of five SNPs (single nucleotide polymorphisms) within ptgs2 and nine SNPs within dnah5 in chickens in different latitudes, suggesting strong selective pressure of these two genes in chickens. We provide a novel insight into the genetic adaptation in chickens to cold environments, and provide a reference for evaluating and developing adaptive chicken breeds in cold environments.

Eye-Gaze Controlled Wheelchair Based on Deep Learning.

In this paper, we design a technologically intelligent wheelchair with eye-movement control for patients with ALS in a natural environment. The system consists of an electric wheelchair, a vision system, a two-dimensional robotic arm, and a main control system. The smart wheelchair obtains the eye image of the controller through a monocular camera and uses deep learning and an attention mechanism to calculate the eye-movement direction. In addition, starting from the relationship between the trajectory of the joystick and the wheelchair speed, we establish a motion acceleration model of the smart wheelchair, which reduces the sudden acceleration of the smart wheelchair during rapid motion and improves the smoothness of the motion of the smart wheelchair. The lightweight eye-movement recognition model is transplanted into an embedded AI controller. The test results show that the accuracy of eye-movement direction recognition is 98.49%, the wheelchair movement speed is up to 1 m/s, and the movement trajectory is smooth, without sudden changes.

Design of Wideband High-Gain Patch Antenna Array for High-Temperature Applications.

A low-profile, wideband, and high-gain antenna array, based on a novel double-H-shaped slot microstrip patch radiating element and robust against high temperature variations, is proposed in this work. The antenna element was designed to operate in the frequency range between 12 GHz and 18.25 GHz, with a 41.3% fractional bandwidth (FBW) and an obtained peak gain equal to 10.2 dBi. The planar array, characterized by a feed network with a flexible 1 to 16 power divider, comprised 4 × 4 antenna elements and generated a pattern with a peak gain of 19.1 dBi at 15.5 GHz. An antenna array prototype was fabricated, and the measurements showed good agreement with the numerical simulations as the manufactured antenna operated in the range of 11.4-17 GHz, with a 39.4% FBW, and the peak gain at 15.5 GHz was 18.7 dBi. The high-temperature simulated and experimental results, performed in a temperature chamber, demonstrated that the array performance was stable in a wide temperature range, from -50 °C to 150 °C.

Combing remote sensing information entropy and machine learning for ecological environment assessment of Hefei-Nanjing-Hangzhou region, China.

Urban ecological environment is the basis of citizens' survival and development. A rapid and objective urban ecological environment assessment (UEEA) plays an important role in the urban sustainable development and environment protection. This study established an improved urban ecological comfort index (UECIIMP), which is based on our previous UECI and fully composed of four remote sensing indicators: normalized difference vegetation index (NDVI), normalized difference built-up index (NDBI), land surface temperature (LST), and aerosol optical depth (AOD), representing the greenness, dryness, heat, and atmospheric turbidity, respectively. Combining the entropy method and random forest (RF) algorithm, the weights of four indicators were calculated. To improve the accuracy of UECIIMP, the gap-filled quarterly mean results of each indicator with 30m resolution were obtained using the harmonic analysis of time series (HANTS) method and spatial-temporal information fusion based on non-local means filter (STNLFFM). UECIIMP was applied to the Hefei-Nanjing-Hangzhou Region to explore its spatiotemporal changes and response characteristics. Results show that the weights of UECIIMP fluctuate slightly (within 10%) before and after sensitivity analysis, with good stability and reliability. UECIIMP in Hangzhou > Hefei ≈ Nanjing, spring ≈ autumn > summer â‰« winter. From 2009 to 2019, UECIIMP has improved in all 33 districts of the Hefei-Nanjing-Hangzhou Region. The significant improvement of UECIIMP in 2014-2019 is 4.3 times than that in 2009-2014. The correlation between UECIIMP and economic index indicates that economic development has a positive impact on the urban ecological environment. The significant degradation of UECIIMP in the urban expansion area demonstrates a negative impact on the local environment from urban expansion.

In Vivo Metabolite Profiling of DMU-212 in ApcMin/+ Mice Using UHPLC-Q/Orbitrap/LTQ MS.

3,4,5,4'-Trans-tetramethoxystilbene (Synonyms: DMU-212) is a resveratrol analogue with stronger antiproliferative activity and more bioavailability. However, the metabolite characterization of this component remains insufficient. An efficient strategy was proposed for the comprehensive in vivo metabolite profiling of DMU-212 after oral administration in ApcMin/+ mice based on the effectiveness of the medicine. Ultra-high performance liquid chromatography-quadrupole/orbitrap/linear ion trap mass spectrometry (UHPLC-Q/Orbitrap/LTQ MS) in the AcquireXTM intelligent data acquisition mode, combining the exact mass and structural information, was established for the profiling and identification of the metabolites of DMU-212 in vivo, and the possible metabolic pathways were subsequently proposed after the oral dose of 240mg/kg for 3 weeks in the colorectal adenoma (CRA) spontaneous model ApcMin/+ mice. A total of 63 metabolites of DMU-212 were tentatively identified, including 48, 48, 34 and 28 metabolites in the ApcMin/+ mice's intestinal contents, liver, serum, and colorectal tissues, respectively. The metabolic pathways, including demethylation, oxidation, desaturation, methylation, acetylation, glucuronide and cysteine conjugation were involved in the metabolism. Additionally, further verification of the representative active metabolites was employed using molecular docking analysis. This study provides important information for the further investigation of the active constituents of DMU-212 and its action mechanisms for CRA prevention.

Ecological risk assessment and restoration area identification of Pengyang County on the basis of the landscape pattern and function.

The joint landscape ecological risk as well as ecological corridors for ecological restoration area identification is of great significance to the past evolution and future development of landscapes. Ecological risks were assessed based on the landscape pattern and functional changes in Pengyang County in 2000, 2010, and 2020; ecological restoration areas were divided based on ecological risks and security pattern. Results showed that the ecological risk types in Pengyang County were mainly low risk from 2000 to 2010 and distributed in the central region, while the high-risk areas increased from 2010 to 2020 and were concentrated in the southern residential area. According to a comprehensive assessment of the landscape ecological risks, an ecological security pattern consisting of 17 ecological source points and 34 potential ecological corridors with an average length of 6.57 km was identified. Three ecological restoration areas were eventually identified: mining restoration areas, mountain restoration area, and urban restoration area. Our results would provide an important perspective for the sustainable development of regional natural landscape resources.

Field assessment of straw pellet combustion in improved heating stoves in rural Northeast China.

Straw pellets are widely promoted and expected to be a cleaner alternative fuel to unprocessed crop residues and raw coal in rural China. However, the effectiveness of these dissemination programs is not well evaluated. In this field study, emission characteristics of burning straw pellets, raw coal, and unprocessed corn cobs in heating stoves were investigated in a pilot village in Northeast China. Emission measurements covering the whole combustion cycle (ignition, flaming, and smoldering phases) shows the promotion of improved heating stoves and straw pellets could reduce pollutant emissions (e.g., SO2 and CO), but increase NOX and PM2.5 emissions compared to the initial stove-fuel use pattern in the studied area. There is a significant variance in emission characteristics between different combustion phases. The normalized emission concentrations of the different stove-fuel combinations were higher than the limits in the Chinese national standard for heating stoves, indicating that the standard is not met for real-world emissions. Coal consumption was lower than official data. Household surveys were conducted to identify the barriers to fuel and stove access associated with existing promotion strategies, management, and policies. The pilot program was of the typical "subsidy-and-policy-dependence" pattern and was unlikely to be implemented on a large scale. Technological innovation, operational optimization, and proper policies considering the local socioeconomic factors are needed to sustain the promotion of biomass straw pellets and stoves.

GSK1702934A and M085 directly activate TRPC6 via a mechanism of stimulating the extracellular cavity formed by the pore helix and transmembrane helix S6.

Transient receptor potential canonical (TRPC) channels, as important membrane proteins regulating intracellular calcium (Ca2+i) signaling, are involved in a variety of physiological and pathological processes. Activation and regulation of TRPC are more dependent on membrane or intracellular signals. However, how extracellular signals regulate TRPC6 function remains to be further investigated. Here, we suggest that two distinct small molecules, M085 and GSK1702934A, directly activate TRPC6, both through a mechanism of stimulation of extracellular sites formed by the pore helix (PH) and transmembrane (TM) helix S6. In silico docking scanning of TRPC6 identified three extracellular sites that can bind small molecules, of which only mutations on residues of PH and S6 helix significantly reduced the apparent affinity of M085 and GSK1702934A and attenuated the maximal response of TRPC6 to these two chemicals by altering channel gating of TRPC6. Combing metadynamics, molecular dynamics simulations, and mutagenesis, we revealed that W679, E671, E672, and K675 in the PH and N701 and Y704 in the S6 helix constitute an orthosteric site for the recognition of these two agonists. The importance of this site was further confirmed by covalent modification of amino acid residing at the interface of the PH and S6 helix. Given that three structurally distinct agonists M085, GSK1702934A, and AM-0883, act at this site, as well as the occupancy of lipid molecules at this position found in other TRP subfamilies, it is suggested that the cavity formed by the PH and S6 has an important role in the regulation of TRP channel function by extracellular signals.

General Bottom-Up Colloidal Synthesis of Nano-Monolayer Transition-Metal Dichalcogenides with High 1T'-Phase Purity.

Phase engineering of nanomaterials provides a promising way to explore the phase-dependent physicochemical properties and various applications of nanomaterials. A general bottom-up synthesis method under mild conditions has always been challenging globally for the preparation of the semimetallic phase-transition-metal dichalcogenide (1T'-TMD) monolayers, which are pursued owing to their unique electrochemical property, unavailable in their semiconducting 2H phases. Here, we report the general scalable colloidal synthesis of nanosized 1T'-TMD monolayers, including 1T'-MoS2, 1T'-MoSe2, 1T'-WS2, and 1T'-WSe2, which are revealed to be of high phase purity. Moreover, the surfactant-reliant stacking-hinderable growth mechanism of 1T'-TMD nano-monolayers was unveiled through systematic experiments and theoretical calculations. As a proof-of-concept application, the 1T'-TMD nano-monolayers are used for electrocatalytic hydrogen production in an acidic medium. The 1T'-MoS2 nano-monolayers possess abundant in-plane electrocatalytic active sites and high conductivity, coupled with the contribution of the lattice strain, thus exhibiting excellent performance. Importantly, the catalyst shows impressive endurability in electroactivity. Our developed general scalable strategy could pave the way to extend the synthesis of other broad metastable semimetallic-phase TMDs, which offer great potential to explore novel crystal phase-dependent properties with wide application development for catalysis and beyond.