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Abstract Background Macrophages are the primary innate immune cells encountered by the invading coronaviruses, and their abilities to initiate inflammatory reactions, to maintain the immunity homeostasis by differential polarization, to train the innate immune system by epigenic modification have been reported in laboratory animal research. Methods In the current in vitro research, murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus, a coronavirus existed in mouse. At 3‐, 6‐, 12‐, 24‐, and 48‐h post infection (hpi.), the attached cells were washed with PBS and harvested in Trizol reagent. Then The harvest is subjected to transcriptome sequencing. Results The transcriptome analysis showed the immediate (3 hpi.) up regulation of DEGs related to inflammation, like Il1b and Il6. DEGs related to M2 differential polarization, like Irf4 showed up regulation at 24 hpi., the late term after viral infection. In addition, DEGs related to metabolism and histone modification, like Ezh2 were detected, which might correlate with the trained immunity of macrophages. Conclusions The current in vitro viral infection study showed the key innated immunity character of macrophages, which suggested the replacement value of viral infection cells model, to reduce the animal usage in preclinical research.

Clinical trials previously demonstrated the notable capacity to elicit visual percepts in individuals with visual impairments caused by retinal diseases by electrically stimulating the remaining neurons on the retina. However, these implants restored very limited visual acuity and required transcutaneous cables traversing the eyeball, leading to reduced reliability and complex surgery with high postoperative infection risks. To overcome the limitations imposed by cables, a retinal implant architecture in which near-infrared illumination carries both power and data through the pupil to a digital stimulation controller is presented. A high efficiency multi-junction photovoltaic cell transduces the optical power to a CMOS stimulator capable of delivering flexible interleaved sequential stimulation through a diamond microelectrode array. To demonstrate the capacity to elicit a neural response with this approach while complying with the optical irradiance limit at the pupil, fluorescence imaging with a calcium indicator is used on a degenerate rat retina. The power delivered by the laser at the permissible irradiance of 4 mW/mm2 at 850 nm is shown to be sufficient to both power the stimulator ASIC and elicit a response in retinal ganglion cells (RGCs), with the ability to generate of up to 35 000 pulses per second at the average stimulation threshold. This confirms the feasibility of generating a response in RGCs with an infrared-powered digital architecture capable of delivering complex sequential stimulation patterns at high repetition rates, albeit with some limitations.

Abstract Introduction The intestinal microbiota plays a crucial role in health and disease. This study aimed to assess the composition and functional diversity of the intestinal microbiota in donkeys and cows by examining samples collected from different segments of the digestive tract using two distinct techniques: direct swab sampling and faecal sampling. Results In this study, we investigated and compared the effects of multiple factors on the composition and function of the intestinal microbial community. Approximately 300 GB of metagenomic sequencing data from 91 samples obtained from various segments of the digestive tract were used, including swabs and faecal samples from monogastric animals (donkeys) and polygastric animals (cows). We assembled 4,004,115 contigs for cows and 2,938,653 contigs for donkeys, with a total of 9,060,744 genes. Our analysis revealed that, compared with faecal samples, swab samples presented a greater abundance of Bacteroidetes, whereas faecal samples presented a greater abundance of Firmicutes. Additionally, we observed significant variations in microbial composition among different digestive tract segments in both animals. Our study identified key bacterial species and pathways via different methods and provided evidence that multiple factors can influence the microbial composition. These findings provide new insights for the accurate characterization of the composition and function of the gut microbiota in microbiome research. Conclusions The results obtained by both sampling methods in the present study revealed that the composition and function of the intestinal microbiota in donkeys and cows exhibit species-specific and region-specific differences. These findings highlight the importance of using standardized sampling protocols to ensure accurate and consistent characterization of the intestinal microbiota in various animal species. The implications and underlying mechanisms of these associations provide multiple perspectives for future microbiome research.

Abstract Surface design by tailoring topographical features and interface function groups to modulate dynamic or kinetic behaviors of liquid droplets, has been an increasing hotspot due to its broad spectrum of applications in biochemical diagnosis, microfabrication, and energy conversion systems. Here we report an engineered surface decorated by packed nanosized caltrops resulting from two perfectly articulated oxidation processes, where self-assembled nanoislands generated in the 1st plasma oxidation serve as protective masks in the 2nd chemical oxidation. As caltrops per design can effectively block lateral motion, the present surface can anchor contact lines of advancing water films when being hydrophilic and selectively capture impinging droplets when being hydrophobic. Furthermore, biphilic patterns can be readily obtained by integrating nanocaltrops with other surface asperities, engendering directional droplet maneuvering and designated droplet arraying. This work provides guidelines in designing nanostructures that achieve on-demand manipulation of droplets and flow patterns for multifunctional applications.

Abstract Electrocatalysts are extensively employed to suppress the shuttling effect in lithium-sulfur (Li-S) batteries. However, it remains challenging to probe the sulfur redox reactions and mechanism at the electrocatalyst/LiPS interface after the active sites are covered by the solid discharge products Li2S/Li2S2. Here, we demonstrate the intrinsic autocatalytic activity of the Li2S (100) plane towards lithium polysulfides on single-atom nickel (SANi) electrocatalysts. Guided by theoretical models and experimental data, it is concluded that LiPS dissociates into Li2S2 and short-chain LiPS on the Li2S (100) plane. Subsequently, Li2S2 undergoes further lithiation to Li2S on the Li2S (100) surface, generating a new Li2S (100) layer, thus enabling the autocatalytic formation of a new Li2S (100) surface. Benefiting from the autocatalytic growth of Li2S, the concentration of LiPS in the electrolyte remains at a lower level, enabling Li-S batteries under high loading and low electrolyte conditions to exhibit superior electrochemical performance.

Abstract Bamboo is an ideal green building material with excellent mechanical properties. Phosphogypsum (PG) is a kind of solid waste residue which is in urgent need of resource utilization and has been used as construction material. In this paper, a kind of round bamboo-fiber reinforced phosphogypsum composite short column was proposed. Axial compression tests of pure bamboo columns, bamboo columns filled with phosphogypsum inside, bamboo columns with phosphogypsum outside and bamboo columns with phosphogypsum inside and outside were carried out to explore the failure mode and mechanical properties of the short columns. The effects of the parameters include bamboo node, hose hoops, size of the bamboo tube and the strength of phosphogypsum on the mechanical properties of the short columns were analyzed, and the theoretical calculation method of the bearing capacity of the short columns was put forward. The results show that the bamboo nodes and hose hoops can improve the bearing capacity, initial stiffness and ductility of the column. The larger the size of the bamboo tube, the better the mechanical properties of the short column. The bearing capacity of round bamboo—phosphogypsum composite short column is higher than that of pure bamboo column. The ductility of bamboo columns with phosphogypsum outside is obviously higher than that of pure bamboo columns. The finite element analysis results are in good agreement with the test results. The theoretical calculation method of the bearing capacity of columns considering the strength reduction coefficient, the bamboo node effect coefficient and the constraint effect in this paper has high accuracy.

Abstract Atherosclerosis, a slowly progressing inflammatory disease, is characterized by the presence of monocyte‐derived macrophages. Interventions targeting the inflammatory characteristics of atherosclerosis hold promising potential. Although interleukin (IL)‐10 is widely acknowledged for its anti‐inflammatory effects, systemic administration of IL‐10 has limitations due to its short half‐life and significant systemic side effects. In this study, we aimed to investigate the effectiveness of an approach designed to overexpress IL‐10 in macrophages and subsequently introduce these genetically modified cells into ApoE−/− mice to promote atherosclerosis regression. We engineered RAW264.7 cells to overexpress IL‐10 (referred to as IL‐10M) using lentivirus vectors. The IL‐10M exhibited robust IL‐10 secretion, maintained phagocytic function, improved mitochondrial membrane potentials, reduced superoxide production and showed a tendency toward the M2 phenotype when exposed to inflammatory stimuli. IL‐10M can selectively target plaques in ApoE−/− mice and has the potential to reduce plaque area and necrotic core at both early and late stages of plaque progression. Moreover, there was a significant reduction in MMP9, a biomarker associated with plaque rupture, in IL‐10M‐treated plaques from both the early and late intervention groups. Additionally, the administration of IL‐10M showed no obvious side effects. This study serves as proof that cell therapy based on anti‐inflammatory macrophages might be a promising strategy for the intervention of atherosclerosis.

Abstract Small extracellular vesicles (sEVs) act as a critical mediator in intercellular communication. Compared to sEVs derived from in vitro sources, tissue‐derived sEVs can reflect the in vivo signals released from specific tissues more accurately. Currently, studies on the role of sEVs in the cochlea have relied on studying sEVs from in vitro sources. This study evaluates three cochlear tissue digestion and cochlear tissue‐derived sEV (CDsEV) isolation methods, and first proposes that the optimal approach for isolating CDsEVs using collagenase D and DNase І combined with sucrose density gradient centrifugation. Furthermore, it comprehensively investigates CDsEV contents and cell origins. Small RNA sequencing and proteomics are performed to analyze the miRNAs and proteins of CDsEVs. The miRNAs and proteins of CDsEVs are crucial for maintaining normal auditory function. Among them, FGFR1 in CDsEVs may mediate the survival of cochlear hair cells via sEVs. Finally, the joint analysis of single CDsEV sequencing and single‐cell RNA sequencing data is utilized to trace cellular origins of CDsEVs. The results show that different types of cochlear cells secrete different amounts of CDsEVs, with Kölliker's organ cells and supporting cells secrete the most. The findings are expected to enhance the understanding of CDsEVs in the cochlea.

Utricle is an important vestibular sensory organ for maintaining balance. 3,3′-iminodipropionitrile (IDPN), a prototype nitrile toxin, has been reported to be neurotoxic and vestibulotoxic, and can be used to establish an in vivo damage model of vestibular dysfunction. However, the mechanism of utricular HCs damage caused by IDPN is unclear. Here, we first studied mice balance behavior and HCs damage in IDPN utricle damage model, and found that IDPN injection in vivo can cause vestibular dysfunction and HCs damage, which is more pronounced than neomycin damage model. Then we used RNA-seq to characterize the transcriptome of IDPN damaged utricle in detail to identify genes and pathways that play roles in this process. We found 1,165 upregulated genes and 1,043 downregulated genes in IDPN damaged utricles, and identified that NF-κB pathway and TNF pathway may play important roles in IDPN damage model. Our study provides details of transcriptome of IDPN utricle damage model for further study of vestibular dysfunction.

Abstract Insufficient mechanical loading impairs fracture healing; however, the underlying mechanisms remain unclear. Increasing evidence indicates that Piezo1 plays an important role in fracture healing, although the effect of Piezo1 on the endochondral ossification of chondrocytes has been overlooked. This study reports that mechanical unloading down‐regulates the expression of Piezo1 in chondrocytes and leads to fracture nonunion. Single‐cell sequencing of calluses revealed that specific deletion of Piezo1 in chondrocytes upregulated the expression of apolipoprotein E (ApoE) in hypertrophic chondrocytes, resulting in delayed cartilage‐to‐bone transition due to enhanced chondrocyte senescence. Based on these results, an injectable and thermosensitive hydrogel is developed, which released an ApoE antagonist in situ at the fracture site. This hydrogel effectively attenuated chondrocyte senescence and, thus, promoted cartilage‐to‐bone transition as well as the fracture healing process. Overall, this data provide a new perspective on the activity of chondrocytes in fracture healing and a new direction for the treatment of fracture nonunion caused by insufficient mechanical loading.

Modular Multilevel Converters (MMCs) play a crucial role in high-voltage DC (HVDC) systems due to their adaptable control and swift response capabilities. However, AC side faults could introduce asymmetric double-line frequency components into the MMC's circulating current, jeopardizing DC bus stability. Although strategies to mitigate DC side fluctuations are well-established, a detailed comparison of their operational impacts remains unexplored. The operational effects of MMCs under AC side faults are firstly examined in this study, including issues related to grid-connected current asymmetry and DC bus current fluctuations. Subsequently, two targeted control schemes are devised based on the goals of suppressing the double-line frequency components and only the zero-sequence components of circulating current. Through simulation, these approaches are contrasted, delineating their advantages and disadvantages in terms of circulating current suppression, submodules(SMs) capacitance voltage fluctuation, and other performance metrics, which could provide a foundational reference for designing and selecting MMC control strategies under AC side faults.

Abstract Electron paramagnetic resonance (EPR) studies were performed on La0.88Sr0.12MnO3 (LSMO) nanocrystalline together with the measurement of its magnetization. Various spectrum parameters including line width, effective g-value and double-integrated intensities have been analyzed in detail. We found nonlinear behavior occurred in the inverse susceptibility far above the Curie temperature T C, indicating short-range ferromagnetic (FM) clusters and Griffiths-like phase behavior in the paramagnetic (PM) phase. Based on the variation of EPR spectra, except for a typical PM resonance peak, an extra resonance signal was observed in the lower field region and developed as temperature decreased from 320 K to 110 K, which gave a direct evidence of the existence of FM cluster in the PM region of LSMO nanocrystalline. We proposed that the appearance of the Griffiths phase was due to the short FM correlation in the PM regime enhanced by surface spin ordering.

Cold significantly impacts the growth and development of tea plants, thereby affecting their economic value. Receptor-like kinases (RLKs) are thought to play a pivotal role in signaling the plant's response to cold and regulating cold tolerance. Among the RLK subfamilies, wall-associated receptor-like kinases (WAKs) have been investigated across various plant species and have been shown to regulate cell growth and stress responses. However, the function of WAK genes in response to cold stress in tea has yet to be studied. In a previous investigation, we identified the WAK gene family from Camellia sinensis and isolated a specific WAK gene, CsWAK12, which is induced by abiotic stresses. Here, we demonstrate that CsWAK12 is involved in the regulation of cold tolerance in tea plants. CsWAK12 was rapidly induced by cold, peaking at 3 hours after treatment at 4°C (10-fold increase). Heterologous overexpression of CsWAK12 (35S:CsWAK12) in Arabidopsis promoted plant growth by enhancing root length and seed size under normal conditions, although it reduced cold resistance compared to the wild type. Under cold stress, the transgenic plants exhibited a lower survival rate and significantly altered levels of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content compared to the wild type (WT). Furthermore, the expression of C-repeat/dehydration-responsive element binding factor (CBF) genes was diminished in CsWAK12-overexpressing transgenic Arabidopsis plants following cold treatment. Transcriptome analysis revealed that genes associated with the CBF pathway, such as transcription factor genes (ERF53, ERF54, and DREB2A) were markedly reduced in the overexpression line. These data suggest that CsWAK12 acts as a negative regulator, reducing the cold tolerance of transgenic Arabidopsis by mediating the CBF pathway. Therefore, CsWAK12 may serve as a candidate gene for the molecular breeding of cold resistance in tea plants.

Epilepsy is an irregular and recurrent cerebral dysfunction that significantly impacts the affected individual's social functionality and quality of life. This study aims to integrate cognitive dynamic attributes of the brain into seizure prediction, evaluating the effectiveness of various characterization perspectives for seizure prediction, while delving into the impact of varying fragment lengths on the performance of each characterization. We adopted microstate analysis to extract the dynamic properties of cognitive states, calculated the EEG-based and microstate-based features to characterize nonlinear attributes, and assessed the power values across different frequency bands to represent the spectral information of the EEG. Based on the aforementioned characteristics, the predictor achieved a sensitivity of 93.82% on the private FH-ZJU seizure dataset and 93.22% on the Siena Scalp EEG dataset. The study outperforms state-of-the-art works in terms of sensitivity metrics in seizure prediction, indicating that it is crucial to incorporate cognitive dynamic attributes of the brain in seizure prediction.

Abstract The electronic orders in kagome materials have emerged as a fertile platform for studying exotic quantum states, and their intertwining with the unique kagome lattice geometry remains elusive. While various unconventional charge orders with broken symmetry is observed, the influence of kagome symmetry on magnetic order has so far not been directly observed. Here, using a high‐resolution magnetic force microscopy, it is, for the first time, observed a new lattice form of noncollinear spin textures in the kagome ferromagnet in zero magnetic field. Under the influence of the sixfold rotational symmetry of the kagome lattice, the spin textures are hexagonal in shape and can further form a honeycomb lattice structure. Subsequent thermal cycling measurements reveal that these spin textures transform into a non‐uniform in‐plane ferromagnetic ground state at low temperatures and can fully rebuild at elevated temperatures, showing a strong second‐order phase transition feature. Moreover, some out‐of‐plane magnetic moments persist at low temperatures, supporting the Kane–Mele scenario in explaining the emergence of the Dirac gap. The observations establish that the electronic properties, including both charge and spin orders, are strongly coupled with the kagome lattices.

Summary: Mesoscale to nanoscale three-dimensional (3D) fabrication mostly requires complicated industry processing techniques. Here, we present a protocol for 3D shaping control by solidifying a water-based TiO2 nanofluid drop on a polygonal wettability-patterned surface. We detail the steps for preparing stable TiO2 nanofluid and wettability-patterned surfaces. We then describe the experimental procedure to obtain various and precise 3D morphologies by adjusting the deposited TiO2 nanofluid drop volume. This protocol provides a promising technique for future 3D manufacturing.For complete details on the use and execution of this protocol, please refer to Jiang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

AbstractCamellia tetracocca H.T. Chang 1981 is an important wild relative of cultivated tea plants. Its leaves are widely used by local people to make tea, showing great economic and breeding values. We here report the complete chloroplast genome of C. tetracocca using Illumina sequencing technology. The complete chloroplast genome of C. tetracocca is 157,026 bp in length, and structurally contains a pair of inverted repeat regions (IRa and IRb, 26,052 bp) separated by a large single-copy region (LSC, 86,669 bp) and a small single-copy region (SSC, 18,253 bp). It is composed of 131 predicted genes, including 86 protein-coding genes, 37 transfer RNA genes, and eight ribosomal RNA genes. The overall GC content is 37.31%. Phylogenetic analysis among four Camellia species and 11 other close species reveals a close relationship between C. tetracocca and C. gymnogyna.

To establish the constitutive model of original bamboo, the tensile and compressive tests along the grain of original bamboo were investigated. The original bamboo was graded according to the elastic modulus, and a stress-strain constitutive model of original bamboo was proposed. The results of the study show that the tensile failure mode of original bamboo along the grain is brittle failure, and the compression along the grain is ductile failure. The bamboo was divided into three grades I, II, and III, and the proportion of II and II was more than 80%. A linear constitutive model was used for tension along the grain of original bamboo, a "three-fold" model was used for simplified constitutive model for compression along the grain, and the Sargin model was used for accurate constitutive model. The classification method proposed in this paper can result in the efficient utilization of bamboo resources, and the proposed constitutive model can promote the analysis and engineering application of original bamboo architecture.

Early non-destructive detection of stress effect is crucial for efficient breeding strategies and germplasm characterization. Recently developed hyperspectral technologies allow to perform fast real-time phenotyping through reflectance-based vegetation indices. However, efficiency of these vegetation indices has to be validated for each crop in different environment. The aim of this study was to reveal efficient vegetation indices for phenotyping of abiotic stress (cold, freezing and nitrogen deficiency) response in tea plant. Among 31 studied VIs, few indices were efficient to distinguish tolerant and susceptible tea plants under abiotic stress: ZMI (Zarco-Tejada & Miller Index), VREI1,2,3 (Vogelmann Red Edge Indices), RENDVI (Red Edge Normalized Difference Vegetation Index), CTR1 and CTR2 (Carter Indices). Most of these indices are calculated based on reflectance in near-infrared area at 705–760 nm, indicating this range as promising for tea germplasm characterization under abiotic stresses. Tolerant tea plants showed the following values under freezing: ZMI ≥1.90, VREI1 ≥ 1.40, RENDVI ≥0.38, Ctr1 ≤ 1.74. The leaf N-content was positively correlated (Pearson's) with the following indices ZMI, VREI1, RENDVI, while negatively correlated with CTR, and VREI2,3. These results will be useful for tea germplasm management, genomics and breeding research aimed at abiotic stress tolerance of tea plant.

There are still some technical issues involved in laser welding of aluminum alloys, such as porosity, cracking, deformation, and so forth. In this study, AA6061-T6 sheets of 2.54 mm in thickness were welded by a disk laser in the bead-on-plate with two different welding parameter sets. Full penetration depths were achieved with decent surface appearances for both cases. The digital image correlation method was successfully applied in experiments to identify material model parameters of tensile welded specimens from various weldment regions. The identified parameters were utilized to numerically simulate the uniaxial tensile tests of laser-welded specimens. The effect of welded joint geometry on global tensile responses was investigated in experimentally-guided finite element modeling. With the help of X-ray computed microtomography, internal defects of the welded bead were detected and used as an input variable in the simulations. Strain development was observed through experimental and numerical data. The results showed that axial deformation was initiated at the top surface of welded metals. The considerable axial deformation occurred at the bottom surface (weld root) of the welded joint just before failure. The numerical results indicated that the geometry of welded joints greatly affected tensile responses. The results also concluded that the diameter of a single void significantly influenced tensile responses compared to its distributed location and the total volume of multiple voids with smaller sizes. Compared between the two sets of welding parameter sets used in this study, the welded joints of this particular AA6061-T6 material with the first parameter set of 2.40 kW laser power and 1.27 m/min traveling speed employed could give better tensile properties and be verified by both experimental and numerical results.

Small radius curved sections of two-lane secondary highways have low technical indicators, complex alignments, and frequent accidents. In order to improve the safety of traffic operation, the article investigates the curved sections of two-lane secondary highways with different radii and obtains the travelling speeds of different vehicle types at different section locations. By studying the trajectory characteristics and speed characteristics of vehicles travelling in curves, the velocity difference ratio, which responds to the continuity of driving speed, was defined. Then, based on this, this paper investigates the vehicle motion law of small radius curved road sections. The results show that the speed change of large cars in small radius curves is similar to a “U'' shape, while the speed change of small cars is similar to a “V'' shape. The speed adjustments of the larger cars occur mainly within the range of gentle curves, whereas the speed changes of the smaller cars are large throughout the range of curves. There is a significant exponential function relationship between curve radius and 85 % percentile speed, from which the curve radius threshold can be predicted. This provides a basis for engineering construction of curved road sections and optimization of curve design indicators, which greatly improves the traffic safety level of curved road sections.

Abstract A large number of motor vehicles and non-motorized vehicles mixed in the section of arterial highway crossing the town leads to many traffic problems. Therefore, it is necessary to set up a side divider between motorized and non-motorized lanes, and the appropriate spacing of lateral crossing openings to meet the needs of non-motorized vehicles crossing the highway has become a key issue that must be resolved. This paper investigates the traffic flow characteristics of mixed traffic flow on arterial highways through small town sections, and from the two dimensions of highway access efficiency and the psychological characteristics of cyclists, it calibrates the setting range of the spacing of non-motorized lateral crossing openings under different design speeds, which is used to regulate the behavior of non-motorized vehicles crossing the street, improve the safety level of the highway, reduce the lateral interference of the highway, and improve the road access efficiency. The accuracy of the research results is verified by microscopic simulation experiments, which proves that they can meet good expectations in practical engineering. The research results have theoretical significance and reference value for improving the status quo of machine-non-mixed traffic in the section of arterial highway passing through small towns, and enhancing the efficiency and safety of highway traffic. It also provides corresponding reference for the areas facing similar problems worldwide.

Bamboo has the advantages of a short growth cycle, good mechanical properties, energy savings, and environmental protection. It is regarded as a new building material with great development potential and application prospects. However, current research on the design values of raw bamboo materials is lacking. In this study, the design value of tensile strength of raw bamboo material was determined by a tensile test of the raw bamboo material, and the statistical values of the tensile strength and elastic modulus of the raw bamboo material were obtained. The standard value and resistance uncertainty statistical parameters of the tensile strength of the raw bamboo material were determined. Considering different load combinations and load effect ratios, the relationship between the reliability index and the resistance component coefficient and the optimal resistance partial coefficient under different load combinations were obtained, and the design value of the tensile strength of the raw bamboo material was obtained.

Aroma in food plays an important role in food perception and acceptance, which depends on various mixtures of volatile organic compounds (VOCs). Moreover, VOCs are of great significance for aroma identification. In this study, headspace solid-phase microextraction (HS-SPME) combined with gas chromatography–mass spectrometry (GC-MS) technology was used to determine the VOCs in 10 pear syrups. A total of 127 VOCs were quantitatively determined, including 9 common VOCs and 46 characteristic VOCs of 10 pear syrups. The pear syrups were divided into three categories by cluster analysis, and thirty-eight differential VOCs were obtained using orthogonal partial least squares discrimination analysis (OPLS-DA) and fourteen key VOCs were selected by odor activity value (OAV). It was revealed that the key and common aroma components of pear syrups were butanoic acid, methyl ester, 2-methyl-, methyl ester and Hexanoic acid, and ethyl ester. The characteristic and differential VOCs were 10-Undecen-1-ol, Hexadecanal, n-Propylacetate, Cyclohexanol, 5-methyl-2-(1-methylethyl)-, (1S,2R,5S)-, Methional, Disulfide, dimethyl, 8-Nonenoic acid, ethyl ester, Naphthalene, 1,2-dihydro-1,1,6-trimethyl-, 3H-Purin-6-amine, N,N,3-trimethyl-, 2-Octanol,2,6-dimethyl-, Furyl hydroxymethyl ketone, Heptane, 2,2,4,6,6-pentamethyl-, and Butanoic acid,2-methyl-,methyl ester. The above results showed that different pear syrups had rich diversity in aroma compounds, with some components being shared among them while others are exclusive to specific syrups.

Lithium–sulfur (Li-S) batteries offer a high theoretical energy density but suffer from poor cycling stability and polysulfide shuttling, which limits their practical application. To address these challenges, we developed a PANI-modified MoS2-NG composite, where MoS2 nanoflowers were uniformly grown on graphene oxide (GO) through PANI modification, resulting in an increased interlayer spacing of MoS2. This expanded spacing exposed more active sites, enhancing polysulfide adsorption and catalytic conversion. The composite was used to prepare MoS2-NG/PP separators for Li-S batteries, which achieved a high specific capacity of 714 mAh g−1 at a 3 C rate and maintained a low capacity decay rate of 0.085% per cycle after 500 cycles at 0.5 C. The larger MoS2 interlayer spacing was key to improving redox reaction kinetics and suppressing the shuttle effect, making the MoS2-NG composite a promising material for enhancing the performance and stability of Li-S batteries.

Abstract Chemical short-range-order has been widely noticed to dictate the electrochemical properties of Li-excess cation-disordered rocksalt oxides, a class of cathode based on earth abundant elements for next-generation high-energy-density batteries. Existence of short-range-order is normally evidenced by a diffused intensity pattern in reciprocal space, however, derivation of local atomic arrangements of short-range-order in real space is hardly possible. Here, by a combination of aberration-corrected scanning transmission electron microscopy, electron diffraction, and cluster-expansion Monte Carlo simulations, we reveal the short-range-order is a convolution of three basic types: tetrahedron, octahedron, and cube. We discover that short-range-order directly correlates with Li percolation channels, which correspondingly affects Li transport behavior. We further demonstrate that short-range-order can be effectively manipulated by anion doping or post-synthesis thermal treatment, creating new avenues for tailoring the electrochemical properties. Our results provide fundamental insights for decoding the complex relationship between local chemical ordering and properties of crystalline compounds.

A crack-free high-Mn TWIP steel welding joint with comparable strength and superplastic was obtained via vacuum electron beam welding (VEBW) where the microstructural evolution, mechanical behaviors and strengthening mechanism of welding joint were investigated. The results indicated that the welding joint with a typical nail-shaped welding cross-section was divided into three zones including the base metal (BM), heat-affected zone (HAZ) and fusion zone (FZ). Massive fine AlN-type precipitates with the hexagonal crystal structure were observed in welding join. The orientation relationship between the γ-austenite matrix and AlN precipitates was determined as [001]γ//[2110]AlN. In FZ, small-sized cellular grains or columnar grains with consistent growth directions were combined into large-sized columnar grains with obvious preferential orientation. Compared with the base mantal, the yield strength, ultimate strength and elongation of the VEBWed specimen were slightly reduced by 6.03%, 4.7% and 13.23%, respectively. However, the impact toughness was obviously decreased from the 87.90 J–68.97 J after the VEBW process, which was mainly attributed to the brittle AlN precipitates, inhomogeneous microstructure and back stress induced by the plastic mismatch between gradient grains. The strength contributions of different regions to overall strength including of BM, HAZ and FZ in welding joint were calculated. Here, the dislocation strengthening and precipitation strengthening were the dominant strengthening mechanisms of FZ, which was attributed to the high level of density and massive fine AlN precipitates induced by micro-elements segregations during the VEBW process.

Neuroendocrine prostate neoplasms, encompassing small cell carcinoma, carcinoid, and large cell carcinoma, are infrequently observed in malignant prostate tumors. The occurrence of large cell neuroendocrine prostate cancer (LCNEPC) is exceedingly rare. In this study, the patient initially presented with a persistent dysuria for a duration of one year, accompanied by a serum prostate-specific antigen (PSA) level of 17.83ng/mL. Prostate magnetic resonance imaging (MRI) and chest computed tomography (CT) scan showed that a neoplastic lesion was considered, and prostate biopsy confirmed prostate adenocarcinoma with a Gleason score of 7 (4 + 3). Then, thoracoscopic lung tumor resection was performed, and the pathological examination revealed the presence of primary moderately differentiated invasive adenocarcinoma of the lung and metastatic prostate adenocarcinoma, the Gleason score was 8 (4 + 4). After 1 year of endocrine therapy with goserelin acetate and bicalutamide, he underwent a laparoscopic radical prostatectomy (LRP), the pathological report indicated the presence of adenocarcinoma mixed with NE carcinoma. Two months after the LRP, the patient experienced gross hematuria and sacral tail pain. Further examination revealed multiple metastatic lesions throughout the body. He also underwent transurethral resection of bladder tumor (TURBT) for bladder tumor and received etoposide+ cisplatin chemotherapy three weeks post-surgery. The patient eventually died of multi-organ failure due to myelosuppression after chemotherapy. This case report presents an uncommon instance of LCNEPC with widespread systemic metastases, while also providing a comprehensive review of existing literature to facilitate improved management and treatment strategies for similar patients in subsequent cases.

Degeneration of photoreceptors in the retina is a leading cause of blindness, but commonly leaves the retinal ganglion cells (RGCs) and/or bipolar cells extant. Consequently, these cells are an attractive target for the invasive electrical implants colloquially known as “bionic eyes.” However, after more than two decades of concerted effort, interfaces based on conventional electrical stimulation approaches have delivered limited efficacy, primarily due to the current spread in retinal tissue, which precludes high-acuity vision. The ideal prosthetic solution would be less invasive, provide single-cell resolution and an ability to differentiate between different cell types. Nanoparticle-mediated approaches can address some of these requirements, with particular attention being directed at light-sensitive nanoparticles that can be accessed via the intrinsic optics of the eye. Here we survey the available known nanoparticle-based optical transduction mechanisms that can be exploited for neuromodulation. We review the rapid progress in the field, together with outstanding challenges that must be addressed to translate these techniques to clinical practice. In particular, successful translation will likely require efficient delivery of nanoparticles to stable and precisely defined locations in the retinal tissues. Therefore, we also emphasize the current literature relating to the pharmacokinetics of nanoparticles in the eye. While considerable challenges remain to be overcome, progress to date shows great potential for nanoparticle-based interfaces to revolutionize the field of visual prostheses.

Abstract The reversible transformation of a nanohelix is one of the most exquisite and important phenomena in nature. However, nanomaterials usually fail to twist into helical crystals. Considering the irreversibility of the previously studied twisting forces, the reverse process (untwisting) is more difficult to achieve, let alone the retwisting of the untwisted crystalline nanohelices. Herein, we report a new reciprocal effect between molecular geometry and crystal structure which triggers a twisting-untwisting-retwisting cycle for tri-cobalt salicylate hydroxide hexahydrate. The twisting force stems from competition between the condensation reaction and stacking process, different from the previously reported twisting mechanisms. The resulting distinct nanohelices give rise to unusual structure elasticity, as reflected in the reversible change of crystal lattice parameters and the mutual transformation between the nanowires and nanohelices. This study proposes a fresh concept for designing reversible processes and brings a new perspective in crystallography.

Ischemic stroke is a type of brain dysfunction caused by pathological changes in the blood vessels of the brain which leads to brain tissue ischemia and hypoxia and ultimately results in cell necrosis. Without timely and effective treatment in the early time window, ischemic stroke can lead to long-term disability and even death. Therefore, rapid detection is crucial in patients with ischemic stroke. In this study, we developed a deep learning model based on fusion features extracted from electroencephalography (EEG) signals for the fast detection of ischemic stroke. Specifically, we recruited 20 ischemic stroke patients who underwent EEG examination during the acute phase of stroke and collected EEG signals from 19 adults with no history of stroke as a control group. Afterwards, we constructed correlation-weighted Phase Lag Index (cwPLI), a novel feature, to explore the synchronization information and functional connectivity between EEG channels. Moreover, the spatio-temporal information from functional connectivity and the nonlinear information from complexity were fused by combining the cwPLI matrix and Sample Entropy (SaEn) together to further improve the discriminative ability of the model. Finally, the novel MSE-VGG network was employed as a classifier to distinguish ischemic stroke from non-ischemic stroke data. Five-fold cross-validation experiments demonstrated that the proposed model possesses excellent performance, with accuracy, sensitivity, and specificity reaching 90.17%, 89.86%, and 90.44%, respectively. Experiments on time consumption verified that the proposed method is superior to other state-of-the-art examinations. This study contributes to the advancement of the rapid detection of ischemic stroke, shedding light on the untapped potential of EEG and demonstrating the efficacy of deep learning in ischemic stroke identification.

Camellia atrothea H.T. Chang, H.S. Wang & B.H. Chen 1983 is a native Camellia species in China, which has significant economic and breeding values. Here, we assembled and analyzed the complete chloroplast genome sequence of C. atrothea based on the whole genome sequencing data from Illumina NovaSeq6000 platform. Results show that the complete chloroplast genome of C. atrothea is 157,099 bp in length, and comprises a large single-copy (LSC, 86,643 bp) region, a small single-copy (SSC, 18,276 bp) region, and a pair of inverted repeats (IRs, 26,090 bp) region. Annotation of the C. atrothea chloroplast genome predicts a total of 133 genes, including 88 protein-coding genes, 8 ribosomal RNA genes, and 37 transfer RNA genes. The overall GC content accounts for 37.30% of the genome, which is clearly consistent with that of other previously published Camellia species from section Thea. Phylogenetic analyses of the whole chloroplast genome sequences of 14 Camellia species using Actinidia chinensis as outgroup reveals that C. atrothea has a close relationship with C. leptophylla.

Transcriptional enhancers can be in physical proximity of their target genes via chromatin looping. The enhancer at the β-globin locus (locus control region [LCR]) contacts the fetal-type (HBG) and adult-type (HBB) β-globin genes during corresponding developmental stages. We have demonstrated previously that forcing proximity between the LCR and HBG genes in cultured adult-stage erythroid cells can activate HBG transcription. Activation of HBG expression in erythroid cells is of benefit to patients with sickle cell disease. Here, using the β-globin locus as a model, we provide proof of concept at the organismal level that forced enhancer rewiring might present a strategy to alter gene expression for therapeutic purposes. Hematopoietic stem and progenitor cells (HSPCs) from mice bearing human β-globin genes were transduced with lentiviral vectors expressing a synthetic transcription factor (ZF-Ldb1) that fosters LCR-HBG contacts. When engrafted into host animals, HSPCs gave rise to adult-type erythroid cells with elevated HBG expression. Vectors containing ZF-Ldb1 were optimized for activity in cultured human and rhesus macaque erythroid cells. Upon transplantation into rhesus macaques, erythroid cells from HSPCs expressing ZF-Ldb1 displayed elevated HBG production. These findings in two animal models suggest that forced redirection of gene-regulatory elements may be used to alter gene expression to treat disease.

Laminated van der Waals (vdW) metallic electrodes can improve the contact of 2D electronic devices, but their scalability is usually limited by the transfer process. Here, the authors report a strategy to deposit vdW contacts onto various 2D and 3D semiconductors at the wafer scale.

Abstract Disuse osteoporosis is characterized by decreased bone mass caused by abnormal mechanical stimulation of bone. Piezo1 is a major mechanosensitive ion channel in bone homeostasis. However, whether intervening in the action of Piezo1 can rescue disuse osteoporosis remains unresolved. In this study, a commonly‐used hindlimb‐unloading model is employed to simulate microgravity. By single‐cell RNA sequencing, bone marrow‐derived mesenchymal stem cells (BMSCs) are the most downregulated cell cluster, and coincidentally, Piezo1 expression is mostly enriched in those cells, and is substantially downregulated by unloading. Importantly, activation of Piezo1 by systemically‐introducing yoda1 mimics the effects of mechanical stimulation and thus ameliorates bone loss under simulated microgravity. Mechanistically, Piezo1 activation promotes the proliferation and osteogenic differentiation of Gli1+ BMSCs by activating the β‐catenin and its target gene activating transcription factor 4 (ATF4). Inhibiting β‐catenin expression substantially attenuates the effect of yoda1 on bone loss, possibly due to inhibited proliferation and osteogenic differentiation capability of Gli1+ BMSCs mediated by ATF4. Lastly, Piezo1 activation also slightly alleviates the osteoporosis of OVX and aged mice. In conclusion, impaired function of Piezo1 in BMSCs leads to insufficient bone formation especially caused by abnormal mechanical stimuli, and is thus a potential therapeutic target for osteoporosis.

Plants produce a wide range of bioactive peptides as part of their innate defense mechanisms. With the explosive growth of plant-derived peptides, verifying the therapeutic function using traditional experimental methods are resources and time consuming. Therefore, it is necessary to predict the therapeutic function of plant-derived peptides more effectively and accurately with reduced waste of resources and thus expedite the development of plant peptides. We herein developed a repository of plant peptides predicted to have multiple therapeutic functions, named as MFPPDB (multi-functional plant peptide database). MFPPDB including 1,482,409 single or multiple functional plant origin therapeutic peptides derived from 121 fundamental plant species. The functional categories of these therapeutic peptides include 41 different features such as anti-bacterial, anti-fungal, anti-HIV, anti-viral, and anti-cancer. The detailed physicochemical information of these peptides was presented in functional search and physicochemical property search module, which can help users easily access the peptide information by the plant peptide species, ID, and functions, or by their peptide ID, isoelectric point, peptide sequence, and molecular weight through web-friendly interface. We further matched the predicted peptides to nine state-of-the-art curated functional peptide databases and found that at least 293,408 of the peptides possess functional potentials. Overall, MFPPDB integrated a massive number of plant peptides have single or multiple therapeutic functions, which will facilitate the comprehensive research in plant peptidomics. MFPPDB can be freely accessed through http://124.223.195.214:9188/mfppdb/index.

Booming demand for facilities and infrastructure in Indonesia has led to an increase in construction-related accidents. Court rulings provide valuable data on accident circumstances, which can help improve safety standards. Although information on these accidents is scarce and not systematically consolidated, effective data gathering and analysis can lead to better safety outcomes. This study analyzes 150 court rulings in construction industry accident cases and their related decision frameworks to identify seven risk categories using scenario analysis. The correlative patterns and their associated significance are explored via descriptive statistical analysis, and four categories, namely project, task, accident, and medium, were found to be correlated. The results of the cross-tabulation test between two categories were used to highlight correlated categories. Toll road works accounted for 52% of accident cases, with collisions with construction machinery being the most frequent accident type (36%, 76 cases). Lifting and moving goods had respective phi and Cramer values of 0.534 and 0.001. It is obvious that future safety improvement efforts should focus on roadway projects and utilizing construction vehicles for transportation and lifting work. This can be achieved through increased regulatory compliance, proper utilization of standard operating procedures (SOPs), and ensuring vehicle suitability. The results of this study are highly relevant to workplace health and safety officers and risk management personnel.

Spontaneous droplet jumping and control of dropwise condensation are relevant for water-harvesting, heat transfer and anti-frosting applications. The authors design a superhydrophobic surface with microscale thin-walled lattice structure to achieve effective jumping of droplets with specified radius range.

Superhydrophobic coatings are gaining importance not only in military technology, industrial engineering, power systems and transportation, but also in food science and biomedicine, where they have enormous potential for real-time applications. Many research institutes have recently been working on the development of superhydrophobic blood-repellent tubes to replace clinical heparin-coated tubes during ECMO therapy, but biological toxicity and high blood adhesion have significantly hampered their practical applications. In this study, we created a cardiopulmonary bypass tube with good superhydrophobicity and blood repellency. In terms of biotoxicity, coagulation time, protein and platelet adsorption, the results show that the superhydrophobic-treated tube clotted in 36 min, compared to 21 min for a clinical Bioline heparin-coated tube and 14 min for bare PVC tube. When compared to the bare PVC tube, the clotting time of the superhydrophobic-treated tube was increased by 157% due to the Cassie-Baxter wetting state of the resulting superhydrophobic blood-repellent coating. Meanwhile, the protein and platelet adsorption on the superhydrophobic-treated tube were decreased by 32% and 74%, respectively. It should be noted that we were the first to explain the superhydrophobic anti-platelet adsorption mechanism from the perspective of inhibiting thromboxane-A2 secretion during blood coagulation. Clarification of platelet activation process and activating substances is vital for understanding the anticoagulant properties of superhydrophobic coatings. On the other hand, non-inflammatory response of the organism was confirmed in the vivo experiments and the cell viability after a 48-hour cytotoxicity assay was about 101%, indicating that the superhydrophobic-treated tubes are non-toxic.

Atherosclerosis preferentially develops at bifurcations exposed to disturbed flow. Plexin D1 (PLXND1) responds to mechanical forces and drives macrophage accumulation in atherosclerosis. Here, multiple strategies were used to identify the role of PLXND1 in site-specific atherosclerosis. Using computational fluid dynamics and three-dimensional light-sheet fluorescence-microscopy, the elevated PLXND1 in M1 macrophages was mainly distributed in disturbed flow area of ApoE−/− carotid bifurcation lesions, and visualization of atherosclerosis in vivo was achieved by targeting PLXND1. Subsequently, to simulate the microenvironment of bifurcation lesions in vitro, we co-cultured oxidized low-density lipoprotein (oxLDL)-treated THP-1-derived macrophages with shear-treated human umbilical vein endothelial cells (HUVECs). We found that oscillatory shear induced the increase of PLXND1 in M1 macrophages, and knocking down PLXND1 inhibited M1 polarization. Semaphorin 3E, the ligand of PLXND1 which was highly expressed in plaques, strongly enhanced M1 macrophage polarization via PLXND1 in vitro. Our findings provide insights into pathogenesis in site-specific atherosclerosis that PLXND1 mediates disturbed flow-induced M1 macrophage polarization.

RAS mutations are among the most prevalent oncogenic drivers in cancers. RAS proteins propagate signals only when associated with cellular membranes as a consequence of lipid modifications that impact their trafficking. Here, we discovered that RAB27B, a RAB family small GTPase, controlled NRAS palmitoylation and trafficking to the plasma membrane, a localization required for activation. Our proteomic studies revealed RAB27B upregulation in CBL- or JAK2-mutated myeloid malignancies, and its expression correlated with poor prognosis in acute myeloid leukemias (AMLs). RAB27B depletion inhibited the growth of CBL-deficient or NRAS-mutant cell lines. Strikingly, Rab27b deficiency in mice abrogated mutant but not WT NRAS–mediated progenitor cell growth, ERK signaling, and NRAS palmitoylation. Further, Rab27b deficiency significantly reduced myelomonocytic leukemia development in vivo. Mechanistically, RAB27B interacted with ZDHHC9, a palmitoyl acyltransferase that modifies NRAS. By regulating palmitoylation, RAB27B controlled c-RAF/MEK/ERK signaling and affected leukemia development. Importantly, RAB27B depletion in primary human AMLs inhibited oncogenic NRAS signaling and leukemic growth. We further revealed a significant correlation between RAB27B expression and sensitivity to MEK inhibitors in AMLs. Thus, our studies presented a link between RAB proteins and fundamental aspects of RAS posttranslational modification and trafficking, highlighting future therapeutic strategies for RAS-driven cancers.

Great progress has been made in the development of bifunctional oxide-zeolite catalysts to tackle the selectivity challenge in syngas chemistry. Here the authors show syngas conversion can be steered along a highly active and selective pathway towards light olefins via ketene acetate (acetyl) intermediates.

Summary: Background: Intraplaque haemorrhage (IPH) drives atherosclerosis progression and is a key imaging biomarker of unstable plaques. Non-invasive and sensitive monitoring of IPH is challenging due to the compositional complexity and dynamic nature of atherosclerotic plaques. Magnetic particle imaging (MPI) is a highly sensitive, radiation-free, and no-tissue-background tomographic technique that detects superparamagnetic nanoparticles. Thus, we aimed to investigate whether MPI can in vivo detect and monitor IPH. Methods: Thirty human carotid endarterectomy samples were collected and scanned with MPI. The tandem stenosis (TS) model was employed to establish unstable plaques with IPH in ApoE−/− mice. MPI and 7 T T1-weighted magnetic resonance imaging (MRI) were performed on TS ApoE−/− mice. Plaque specimens were analyzed histologically. Findings: Human carotid endarterectomy samples exhibited endogenous MPI signals, which histologically colocalized with IPH. In vitro experiments identified haemosiderin, a haemoglobin degradation product, as a potential source of MPI signals. Longitudinal MPI of TS ApoE−/− mice detected IPH at unstable plaques, of which MPI signal-to-noise ratio values increased from 6.43 ± 1.74 (four weeks) to 10.55 ± 2.30 (seven weeks) and reduced to 7.23 ± 1.44 (eleven weeks). In contrast, 7 T T1-weighted MRI did not detect the small-size IPH (329.91 ± 226.82 μm2) at four weeks post-TS. The time-course changes in IPH were shown to correlate with neovessel permeability providing a possible mechanism for signal changes over time. Interpretation: MPI is a highly sensitive imaging technology that allows the identification of atherosclerotic plaques with IPH and may help detect and monitor unstable plaques in patients. Funding: This work was supported in part by the Beijing Natural Science Foundation under Grant JQ22023; the National Key Research and Development Program of China under Grant 2017YFA0700401; the National Natural Science Foundation of China under Grant 62027901, 81827808, 81730050, 81870178, 81800221, 81527805, and 81671851; the CAS Youth Innovation Promotion Association under Grant Y2022055 and CAS Key Technology Talent Program; and the Project of High-Level Talents Team Introduction in Zhuhai City (Zhuhai HLHPTP201703).

Driven by the demand to preserve the existing road pavement condition, the issue of selecting maintenance action at the appropriate time under budget limitation has attracted great attention from highway agencies. This study focuses on the strategy of how to manage pavement maintenance budget effectively on road network level based on life cycle cost analysis. The framework of resource-constrained project scheduling problem (RCPSP) is implemented to establish a maintenance action decision-making mechanism for allocating pavement maintenance budgets on the planning and controlling phases. In the RCPSP environment, a two-stage optimization model based on constraint programming techniques is developed to meet two different management goals such as 1. annual budget evaluation from planning points of view, and 2. actual budget adjustment from the controlling point of view, by considering the factor of road usability. Model-I, the life cycle lifespan evaluation model solves the problem of annual budget evaluation to satisfy the maintenance requirements of all road sections. The optimal maintenance plan then can be made to maintain road performance and evaluate annual budget requirement for future years to maximize total maintenance benefits, in terms of the overall maximum pavement lifespan. Based on the suggested results of budget evaluation from Model-I, Model-II, the actual budget adjustment model deals with the actual budget allocation problem of how to keep up the original maintenance budget plan when the actual budget is always awarded insufficiently each year. Finally, the proposed two-stage integrated models provide an optimal maintenance strategy to respond to actual maintenance status and pavement deterioration as feedbacks to the actual budget adjustment model, and recursively make pavement maintenance strategy closer to actual conditions by budget adjustment yearly.

Deep convolutional neural networks have become an indispensable method in remote sensing image scene classification because of their powerful feature extraction capabilities. However, the ability of the models to extract multiscale features and global features on surface objects of complex scenes is currently insufficient. We propose a framework based on global context spatial attention (GCSA) and densely connected convolutional networks to extract multiscale global scene features, called GCSANet. The mixup operation is used to enhance the spatial mixed data of remote sensing images, and the discrete sample space is rendered continuous to improve the smoothness in the neighborhood of the data space. The characteristics of multiscale surface objects are extracted, and their internal dense connection is strengthened by the densely connected backbone network. GCSA is introduced into the densely connected backbone network to encode the context information of the remote sensing scene image into the local features. Experiments were performed on four remote sensing scene datasets to evaluate the performance of GCSANet. The GCSANet achieved the highest classification precision on AID and NWPU datasets and the second-best performance on the UC Merced dataset, indicating the GCSANet can effectively extract the global features of remote sensing images. In addition, the GCSANet presents the highest classification accuracy on the constructed mountain image scene dataset. These results reveal that the GCSANet can effectively extract multiscale global scene features on complex remote sensing scenes. The source codes of this method can be foundin https://github.com/ShubingOuyangcug/GCSANet.

Tea is one of the most consumed and widely planted beverage plant worldwide, which contains many important economic, healthy, and cultural values. Low temperature inflicts serious damage to tea yields and quality. To cope with cold stress, tea plants have evolved a cascade of physiological and molecular mechanisms to rescue the metabolic disorders in plant cells caused by the cold stress; this includes physiological, biochemical changes and molecular regulation of genes and associated pathways. Understanding the physiological and molecular mechanisms underlying how tea plants perceive and respond to cold stress is of great significance to breed new varieties with improved quality and stress resistance. In this review, we summarized the putative cold signal sensors and molecular regulation of the CBF cascade pathway in cold acclimation. We also broadly reviewed the functions and potential regulation networks of 128 cold-responsive gene families of tea plants reported in the literature, including those particularly regulated by light, phytohormone, and glycometabolism. We discussed exogenous treatments, including ABA, MeJA, melatonin, GABA, spermidine and airborne nerolidol that have been reported as effective ways to improve cold resistance in tea plants. We also present perspectives and possible challenges for functional genomic studies on cold tolerance of tea plants in the future.

Colony-stimulating factor 1 (Csf1) is an essential growth factor for osteoclast progenitors and an important regulator for bone resorption. It remains elusive which mesenchymal cells synthesize Csf1 to stimulate osteoclastogenesis. We recently identified a novel mesenchymal cell population, marrow adipogenic lineage precursors (MALPs), in bone. Compared to other mesenchymal subpopulations, MALPs expressed Csf1 at a much higher level and this expression was further increased during aging. To investigate its role, we constructed MALP-deficient Csf1 CKO mice using AdipoqCre. These mice had increased femoral trabecular bone mass, but their cortical bone appeared normal. In comparison, depletion of Csf1 in the entire mesenchymal lineage using Prrx1Cre led to a more striking high bone mass phenotype, suggesting that additional mesenchymal subpopulations secrete Csf1. TRAP staining revealed diminished osteoclasts in the femoral secondary spongiosa region of Csf1 CKOAdipoq mice, but not at the chondral-osseous junction nor at the endosteal surface of cortical bone. Moreover, Csf1 CKOAdipoq mice were resistant to LPS-induced calvarial osteolysis. Bone marrow cellularity, hematopoietic progenitors, and macrophages were also reduced in these mice. Taken together, our studies demonstrate that MALPs synthesize Csf1 to control bone remodeling and hematopoiesis.

Abstract Background The JEV genome is a positive-sense RNA with a highly structured capped 5′UTR, 3′UTR and a large open reading frame. 3′UTR is the untranslated region of flavivirus and has various important functions during viral replication, such as translation, replication and encapsidation. During viral replication, the 3′UTR interacts with viral proteins and host proteins and is required for viral RNA replication and translocation. Methods The expression level of FUBP3 was knocked down by siRNA and Flag-tagged FUBP3 overexpression plasmid was constructed for overexpression. BHK-21 cells were cultured and infected with JEV to investigate the functional role of FUBP3 in the viral infection cycle. Subcellular localization of FUBP3 and viral replication complexes was observed by dual immunofluorescence staining. Results Four host proteins were specifically associated with the 3′UTR of JEV, and FUBP3 was selected to further investigate its potential functional role in the JEV infection cycle. Knockdown of FUBP3 protein resulted in a significant decrease in JEV viral titer, whereas ectopic overexpression of FUBP3 resulted in increased JE viral infectivity. In cells stably knocked down for FUBP3 and then infected with JEV, we found almost no detectable viral NS5 protein. In contrast, when cells stably knocking-down of FUBP3 overexpressed FUBP3, we found a significant increase in viral RNA production over time compared to controls. We also demonstrated that FUBP3 re-localized in the cytoplasm after infection with JEV and co-localized with viral proteins. Exogenous overexpression of FUBP3 was also shown to be located in the JE replication complex and to assist viral replication after JEV infection. Conclusions The overall results suggest that FUBP3 regulates RNA replication of JEV and promotes subsequent viral translation and viral particle production.

The honeycomb lattice with a spin-orbit interaction can give rise to exotic quantum states. With the measurements of bulk properties and inelastic neutron scattering, Lin et al demonstrate the existence of a field induced spin-disordered state in Na2Co2TeO6 and extend the Kitaev model to 3d system.

Abstract SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals. However, it remains unclear whether and how SARS-CoV-2 crosses the blood–brain barrier (BBB). Herein, SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space, as well as in brain microvascular endothelial cells (BMECs) in the infected K18-hACE2 transgenic mice. Moreover, the permeability of the infected vessel was increased. Furthermore, disintegrity of BBB was discovered in the infected hamsters by administration of Evans blue. Interestingly, the expression of claudin5, ZO-1, occludin and the ultrastructure of tight junctions (TJs) showed unchanged, whereas, the basement membrane was disrupted in the infected animals. Using an in vitro BBB model that comprises primary BMECs with astrocytes, SARS-CoV-2 was found to infect and cross through the BMECs. Consistent with in vivo experiments, the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs. Besides, inflammatory responses including vasculitis, glial activation, and upregulated inflammatory factors occurred after SARS-CoV-2 infection. Overall, our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.