The role of gut microbiota in mediating increased toxicity of nano-sized polystyrene compared to micro-sized polystyrene in mice.

Microplastics (MPs) are widespread environmental contaminants that have been detected in animals and humans. However, their toxic effects on terrestrial mammals and the underlying mechanisms are still not well understood. Herein, we explored the role of gut microbiota in mediating the toxicity of micro- and nano-sized polystyrene plastics (PS-MPs/PS-NPs) using an antibiotic depleted mice model. The results showed that PS-MPs and PS-NPs exposure disrupted the composition and structure of the gut microbiota. Specifically, these particles led to an increase in pathogenic Esherichia-shigella, while depleting probiotics such as Akkermansia and Lactobacillus. Comparatively, PS-NPs particles had more pronounced effect, leading to obviously shifted the colon transcriptional profiles characterized by inducing the enrichment of colon metabolism and immune-related pathways (i.e., upregulated in genes like udgh, ugt1a1, ugt1a6a, ugt1a7c and ugt2b34). Additionally, both PS-MPs and PS-NPs induced oxidative stress, gut-liver damage and systemic inflammation in mice. Mechanistically, we confirmed that PS particles disturbed gut microbiota, activating TLR2-My88-NF-κB pathway to trigger the release of inflammatory cytokine IL-1ß and TNF-α. The damage and inflammation caused by both size of PS particles was alleviated when the gut microbiota was depleted. In conclusion, our findings deepen the understanding of the molecule mechanisms by which gut microbiota mediate the toxicity of PS particles, informing health implications of MPs pollution.

Landscape and risk assessment of microplastic contamination in farmed oysters and seawater along the coastline of China.

Microplastic (MP) pollution poses a significant threat to marine ecosystem and seafood safety. However, comprehensive and comparable assessments of MP profiles and their ecological and health in Chinese farming oysters are lacking. This study utilized laser infrared imaging spectrometer (LDIR) to quantify MPs in oysters and its farming seawater at 18 sites along Chinese coastlines. Results revealed a total of 3492 MPs in farmed oysters and seawater, representing 34 MP types, with 20-100 µm MP fragments being the dominant. Polyurethane (PU) emerged as the predominant MP type in oysters, while polysulfones were more commonly detected in seawater. Notably, oysters from the Bohai Sea exhibited a higher abundance of MPs (13.62 ± 2.02 items/g) and estimated daily microplastic intake (EDI, 2.14 ± 0.26 items/g/kg·bw/day), indicating a greater potential health risk in the area. Meanwhile, seawater from the Yellow Sea displayed a higher level (193.0 ± 110.7 items/L), indicating a greater ecological risk in this region. Given the pervasiveness and abundance of PU and its high correlation with other MP types, we proposed PU as a promising indicator for monitoring and assessing the risk MP pollution in mariculture in China. These findings provide valuable insights into the extent and characteristics of MP pollution in farmed oysters and seawater in China.

Dissemination of antibiotic resistance genes from aboveground sources to groundwater in livestock farms.

Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are prevalent in various environments on livestock farms, including livestock waste, soil, and groundwater. Contamination of groundwater by ARB and ARGs in livestock farms is a growing concern as it may have potentially huge risks to human health. However, the source of groundwater-borne ARB and ARGs in animal farms remains largely unknown. In this study, different types of samples including groundwater and its potential contamination sources from aboveground (pig feces, wastewater, and soil) from both working and abandoned swine feedlots in southern China were collected and subjected to metagenomic sequencing and ARB isolation. The source tracking based on metagenomic analysis revealed that 56-95 % of ARGs in groundwater was attributable to aboveground sources. Using metagenomic assembly, we found that 45 ARGs predominantly conferring resistance to aminoglycosides, sulfonamides, and tetracyclines could be transferred from the aboveground sources to groundwater, mostly through plasmid-mediated horizontal gene transfer. Furthermore, the full-length nucleotide sequences of sul1, tetA, and TEM-1 detected in ARB isolates exhibited the close evolutionary relationships between aboveground sources and groundwater. Some isolated strains of antibiotic-resistant Pseudomonas spp. from aboveground sources and groundwater had the high similarity (average nucleotide identity > 99 %). Notably, the groundwater-borne ARGs were identified as mainly carried by bacterial pathogens, potentially posing risks to human and animal health. Overall, this study underscores the dissemination of ARGs from aboveground sources to groundwater in animal farms and associated risks.

S-amlodipine induces liver inflammation and dysfunction through the alteration of intestinal microbiome in a rat model.

S-amlodipine, a commonly prescribed antihypertensive agent, is widely used in clinical settings to treat hypertension. However, the potential adverse effects of long-term S-amlodipine treatment on the liver remain uncertain, given the cautionary recommendations from clinicians regarding its administration in individuals with impaired liver function. To address this, we conducted a study using an eight-week-old male rat model and administered a daily dose of 0.6 ~ 5 mg/kg of S-amlodipine for 7 weeks. Our findings demonstrated that 1.2 ~ 5 mg/kg of S-amlodipine treatment induced liver inflammation and associated dysfunction in rats, further in vitro experiments revealed that the observed liver inflammation and dysfunction were not attributable to direct effects of S-amlodipine on the liver. Metagenome sequencing analysis revealed that S-amlodipine treatment led to alterations in the gut microbiome of rats, with the bloom of E. coli (4.5 ~ 6.6-fold increase) and a decrease in A. muciniphila (1,613.4 ~ 2,000-fold decrease) and B. uniformis (20.6 ~ 202.7-fold decrease), subsequently causing an increase in the gut bacterial lipopolysaccharide (LPS) content (1.4 ~ 1.5-fold increase in feces). S-amlodipine treatment also induced damage to the intestinal barrier and increased intestinal permeability, as confirmed by elevated levels of fecal albumin; furthermore, the flux of gut bacterial LPS into the bloodstream through the portal vein resulted in an increase in serum LPS content (3.3 ~ 4-fold increase). LPS induces liver inflammation and subsequent dysfunction in rats by activating the TLR4 pathway. This study is the first to show that S-amlodipine induces liver inflammation and dysfunction by perturbing the rat gut microbiome. These results indicate the adverse effects of S-amlodipine on the liver and provide a rich understanding of the safety of long-term S-amlodipine administration.

Why flying insects gather at artificial light.

Explanations of why nocturnal insects fly erratically around fires and lamps have included theories of "lunar navigation" and "escape to the light". However, without three-dimensional flight data to test them rigorously, the cause for this odd behaviour has remained unsolved. We employed high-resolution motion capture in the laboratory and stereo-videography in the field to reconstruct the 3D kinematics of insect flights around artificial lights. Contrary to the expectation of attraction, insects do not steer directly toward the light. Instead, insects turn their dorsum toward the light, generating flight bouts perpendicular to the source. Under natural sky light, tilting the dorsum towards the brightest visual hemisphere helps maintain proper flight attitude and control. Near artificial sources, however, this highly conserved dorsal-light-response can produce continuous steering around the light and trap an insect. Our guidance model demonstrates that this dorsal tilting is sufficient to create the seemingly erratic flight paths of insects near lights and is the most plausible model for why flying insects gather at artificial lights.

First Report of Erysiphe astragali Causing Powdery Mildew on Astragalus mongholicus in China.

Astragalus mongholicus Bge. [A. membranaceus Bge. var. mongholicus (Bge.) Hsiao] is a highly valuable perennial medicinal plant mainly distributed in China, whose dry roots are known as Huangqi in traditional Chinese medicine for reinforcing vital energy, strengthening superficial resistance, and promoting tissue regeneration (Lin et al. 2000). A. mongholicus roots of high quality are produced in Northwest and North China. Since July 2021, powdery mildew outbreaks happened annually on the leaves of A. mongholicus in a plantation (123° 56' 40'' E, 47° 22' 20'' N) in Qiqihar city, Heilongjiang Province, China. Disease incidence reached 100% by October (Fig. 1A-C), causing severe impairment of growth. Powdery mildew spots of circular or irregular shapes emerged on upper surface of leaf, resulting in plentiful lesion specks. Dense white hyphae appeared chaotically intertwined. Hyphae were hyaline and highly flexuous, 5.3 - 10.7 µm in diameter (n = 20). Chasmothecia were globose or slightly ovoid-shaped and turned dark brown when matured. Chasmothecia (diameter: 135.2 - 222.9 µm, n = 20) existed abundantly on the diseased leaves in the fields. Conidiophores were 89.0 - 129.9 µm in length (n = 20) and composed of one cylindrical, straight foot cell, followed by two cells and one to three conidia. Conidia were slim ellipsoid-shaped, occasionally ovoid-shaped, measuring 14.6 - 24.7 µm by 6.4 to10.4 µm, length/width ratio was 1.8 - 3.0 (n = 30). Hyphal appressoria were nipple-shaped and appeared in singular, occasionally in pairs. Unbranched germ tube emerged reaching out of the germinating conidia while forming an acute angle with the long axis. Comprehensively, the pathogen exhibited micro-morphology of the genus Erysiphe. For molecular identification, pathogen was carefully scraped off diseased leaves for DNA extraction. We used the DNA samples of three biological replicates for the sequencing of the ITS rDNA fragment (primers by (White et al. 1990). All the samples resulted in an identical ITS sequence (deposited in GenBank as OQ390098.1). It displayed 99.83% identity with OP806835.1 of an E. astragali voucher collected in Iran (Fig. 1D-M, O). Hence, our pathogen was identified as an E. astragali stain. Additionally, we amplified the Mcm7 sequence (using primers by (Ellingham et al. 2019), deposited as OQ397582.1). We propagated 40-day-old A. mongholicus plants via germinating seeds in pot soil and performed pathogenicity tests. Firstly, we incubated detached healthy leaves of propagated plants with severely symptomatic leaves collected from the fields in petri dishes under saturated moisture content and room temperature. Powdery mildew symptoms emerged on each healthy leaf (n = 5) after two weeks. Further, we infected healthy plants (n = 5) by gently pressing and rubbing symptomatic leaves on each healthy leaf, and kept them in a greenhouse (24 ℃, 80% humidity, 16/8-hour light/dark cycle). After a month, symptoms emerged on a number of leaves of each infected plant. We performed micromorphology observation (Fig. 1N-P) and ITS sequencing to confirm that the results fulfilled Koch's postulates. Powdery mildew caused by E. astragali on A. strictus in Tibet (Wang and Jiang 2023) and on A. scaberrimus in Inner Mongolia (Sun et al. 2023) have been reported. Here we report powdery mildew caused by E. astragali on Astragalus mongholicus for the first time. These Astragalus spp. are all acknowledged to have medicinal values in China but their usages are quite different.

Liquid-on-solid heterogeneous nucleation for a general synthesis of yolk-shell nanostructures.

Liquid-on-solid heterogeneous nucleation on solid nanoparticle seeds was achieved. Syrup solutions from a solute-induced phase separation (SIPS) process were heterogeneously nucleated on nanoparticle seeds to form syrup domains, similar to the "seeded growth" method in classical nanosynthesis. The selective inhibition of homogeneous nucleation was also confirmed and exploited for a high-purity synthesis, showing similarity between nanoscale droplets and particles. The seeded-growth of syrup could serve as a general and robust method to one-step fabricate yolk-shell nanostructures, with efficient loading of the dissolved substances.

High-Bonding-Strength Polyimide Films Achieved via Thermal Management and Surface Activation.

In this study, thermal and argon (Ar) plasma/wetting treatments were combined to enhance the bonding strength of polyimide (PI) films. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was used to analyze the changes in the PI imidization degrees. The contact angles of the PI films were also measured. The results show that the contact angles of the fully cured PI films markedly decreased from 78.54° to 26.05° after the Ar plasma treatments. X-ray photoelectron spectroscopy (XPS) analysis was also conducted on the PI surfaces. We found that the intensities of the C-OH and C-N-H bonds increased from 0% to 13% and 29% to 57%, respectively, after Ar plasma activation. Such increases in the C-OH and C-N-H intensities could be attributed to the generation of dangling bonds and the breakage of the imide ring or polymer long chains. Shear tests were also conducted to characterize the bonding strength of the PI films, which, after being treated with the appropriate parameters of temperature, plasma power, and wetting droplets, was found to be excellent at greater than 35.3 MPa.

[Application of tissue culture technology of medicinal plants in sustainable development of Chinese medicinal resources].

Chinese medicinal resources are the cornerstone of the sustainable development of traditional Chinese medicine industry. However, due to the fecundity of species, over-exploitation, and limitations of artificial cultivation, some medicinal plants are depleted and even endangered. Tissue culture, a breakthrough technology in the breeding of traditional Chinese medicinal materials, is not limited by time and space, and can allow the production on an annual basis, which plays an important role in the protection of Chinese medicinal resources. The present study reviewed the applications of tissue culture of medicinal plants in the field of Chinese medicinal resources, including rapid propagation of medicinal plant seedlings, breeding of novel high-yield and high-quality cultivars, construction of a genetic transformation system, and production of secondary metabolites. Meanwhile, the current challenges and suggestions for the future development of this field were also proposed.

Spintronic leaky-integrate-fire spiking neurons with self-reset and winner-takes-all for neuromorphic computing.

Neuromorphic computing using nonvolatile memories is expected to tackle the memory wall and energy efficiency bottleneck in the von Neumann system and to mitigate the stagnation of Moore's law. However, an ideal artificial neuron possessing bio-inspired behaviors as exemplified by the requisite leaky-integrate-fire and self-reset (LIFT) functionalities within a single device is still lacking. Here, we report a new type of spiking neuron with LIFT characteristics by manipulating the magnetic domain wall motion in a synthetic antiferromagnetic (SAF) heterostructure. We validate the mechanism of Joule heating modulated competition between the Ruderman-Kittel-Kasuya-Yosida interaction and the built-in field in the SAF device, enabling it with a firing rate up to 17 MHz and energy consumption of 486 fJ/spike. A spiking neuron circuit is implemented with a latency of 170 ps and power consumption of 90.99 µW. Moreover, the winner-takes-all is executed with a current ratio >104 between activated and inhibited neurons. We further establish a two-layer spiking neural network based on the developed spintronic LIFT neurons. The architecture achieves 88.5% accuracy on the handwritten digit database benchmark. Our studies corroborate the circuit compatibility of the spintronic neurons and their great potential in the field of intelligent devices and neuromorphic computing.

Synergy of Spin-Orbit Torque and Built-In Field in Magnetic Tunnel Junctions with Tilted Magnetic Anisotropy: Toward Tunable and Reliable Spintronic Neurons.

Owing to programmable nonlinear dynamics, magnetic domain wall (DW)-based devices can be configured to function as spintronic neurons, promising to execute sophisticated tasks as a human brain. Developing energy-efficient, CMOS compatible, reliable, and tunable spintronic neurons to emulate brain-inspired processes has been a key research goal for decades. Here, a new type of DW device is reported with biological neuron characteristics driven by the synergistic interaction between spin-orbit torque and built-in field (Hbuilt-in ) in magnetic tunnel junctions, enabling time- and energy-efficient leaky-integrate-and-fire and self-reset neuromorphic implementations. A tilted magnetic anisotropic free layer is proposed and further executed to mitigate the DW retrograde motion by suppressing the Walker breakdown. Complementary experiments and micromagnetic co-simulation results show that the integrating/leaking time of the developed spintronic neuron can be tuned to 12/15 ns with an integrating power consumption of 65 µW, which is 36× and 1.84× time and energy efficient than the state-of-the-art alternatives, respectively. Moreover, the spatial distribution of Hbuilt-in can be modulated by adjusting the width and compensation of the reference layer, facilitating tunable activation function generator exploration. Such architecture demonstrates great potential in both fundamental research and new trajectories of technology advancement for spintronic neuron hardware applications.

Systematic characterization of wing mechanosensors that monitor airflow and wing deformations.

Animal wings deform during flight in ways that can enhance lift, facilitate flight control, and mitigate damage. Monitoring the structural and aerodynamic state of the wing is challenging because deformations are passive, and the flow fields are unsteady; it requires distributed mechanosensors that respond to local airflow and strain on the wing. Without a complete map of the sensor arrays, it is impossible to model control strategies underpinned by them. Here, we present the first systematic characterization of mechanosensors on the dragonfly's wings: morphology, distribution, and wiring. By combining a cross-species survey of sensor distribution with quantitative neuroanatomy and a high-fidelity finite element analysis, we show that the mechanosensors are well placed to perceive features of the wing dynamics relevant to flight. This work describes the wing sensory apparatus in its entirety and advances our understanding of the sensorimotor loop that facilitates exquisite flight control in animals with highly deformable wings.

All-Electrical Control of Compact SOT-MRAM: Toward Highly Efficient and Reliable Non-Volatile In-Memory Computing.

Two-dimensional van der Waals (2D vdW) ferromagnets possess outstanding scalability, controllable ferromagnetism, and out-of-plane anisotropy, enabling the compact spintronics-based non-volatile in-memory computing (nv-IMC) that promises to tackle the memory wall bottleneck issue. Here, by employing the intriguing room-temperature ferromagnetic characteristics of emerging 2D Fe3GeTe2 with the dissimilar electronic structure of the two spin-conducting channels, we report on a new type of non-volatile spin-orbit torque (SOT) magnetic tunnel junction (MTJ) device based on Fe3GeTe2/MgO/Fe3GeTe2 heterostructure, which demonstrates the uni-polar and high-speed field-free magnetization switching by adjusting the ratio of field-like torque to damping-like torque coefficient in the free layer. Compared to the conventional 2T1M structure, the developed 3-transistor-2-MTJ (3T2M) cell is implemented with the complementary data storage feature and the enhanced sensing margin of 201.4% (from 271.7 mV to 547.2 mV) and 276% (from 188.2 mV to 520 mV) for reading "1" and "0", respectively. Moreover, superior to the traditional CoFeB-based MTJ memory cell counterpart, the 3T2M crossbar array architecture can be executed for AND/NAND, OR/NOR Boolean logic operation with a fast latency of 24 ps and ultra-low power consumption of 2.47 fJ/bit. Such device to architecture design with elaborated micro-magnetic and circuit-level simulation results shows great potential for realizing high-performance 2D material-based compact SOT magnetic random-access memory, facilitating new applications of highly reliable and energy-efficient nv-IMC.

Rainfall facilitates the transmission and proliferation of antibiotic resistance genes from ambient air to soil.

Antibiotic resistance is common in bacterial communities and appears to be correlated with human activities. However, the source of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in remote regions remains unclear. In this study, we examined the abundance of ARGs in fine particulate matter (PM2.5) as a carrier throughout the rainfall process (4 mm rain/h) to observe the effects of rainfall on the transmission of ARGs. The results suggested that rainwater served as a reservoir that facilitated the spread of ARGs and that wind and particulate matter (PM) concentrations might be meteorological parameters that influence the distribution of ARGs in rainwater. In addition, soil microcosm experiments were performed to investigate the influence of rainfall on antibiotic resistance in soils with different environmental backgrounds. Rainwater facilitated the proliferation of ARGs and mobile genetic elements (MGEs) from ambient air to soil, and this influence was more obvious in heavy metal-contaminated soil. This is the first study to investigate the routes by which rainfall acts as a mobile reservoir to facilitate the transmission and proliferation of ARGs, and the results indicate the potential source of ARGs in remote regions where humans rarely interfere.

Dragondrop: a novel passive mechanism for aerial righting in the dragonfly.

Dragonflies perform dramatic aerial manoeuvres when chasing targets but glide for periods during cruising flights. This makes dragonflies a great system to explore the role of passive stabilizing mechanisms that do not compromise manoeuvrability. We challenged dragonflies by dropping them from selected inverted attitudes and collected 6-degrees-of-freedom aerial recovery kinematics via custom motion capture techniques. From these kinematic data, we performed rigid-body inverse dynamics to reconstruct the forces and torques involved in righting behaviour. We found that inverted dragonflies typically recover themselves with the shortest rotation from the initial body inclination. Additionally, they exhibited a strong tendency to pitch-up with their head leading out of the manoeuvre, despite the lower moment of inertia in the roll axis. Surprisingly, anaesthetized dragonflies could also complete aerial righting reliably. Such passive righting disappeared in recently dead dragonflies but could be partially recovered by waxing their wings to the anaesthetised posture. Our kinematics data, inverse dynamics model and wind-tunnel experiments suggest that the dragonfly's long abdomen and wing posture generate a rotational tendency and passive attitude recovery mechanism during falling. This work demonstrates an aerodynamically stable body configuration in a flying insect and raises new questions in sensorimotor control for small flying systems.

The prevalence of ampicillin-resistant opportunistic pathogenic bacteria undergoing selective stress of heavy metal pollutants in the Xiangjiang River, China.

The emergence of clinically relevant ß-lactam-resistant bacteria poses a serious threat to human health and presents a major challenge for medical treatment. How opportunistic pathogenic bacteria acquire antibiotic resistance and the prevalence of antibiotic-resistant opportunistic pathogenic bacteria in the environment are still unclear. In this study, we further confirmed that the selective pressure of heavy metals contributes to the increase in ampicillin-resistant opportunistic pathogens in the Xiangjiang River. Four ampicillin-resistant opportunistic pathogenic bacteria (Pseudomonas monteilii, Aeromonas hydrophila, Acinetobacter baumannii, and Staphylococcus epidermidis) were isolated on Luria-Bertani (LB) agar plates and identified by 16S rRNA sequencing. The abundance of these opportunistic pathogenic bacteria significantly increased in the sites downstream of the Xiangjiang River that were heavily influenced by metal mining activities. A microcosm experiment showed that the abundance of ß-lactam resistance genes carried by opportunistic pathogenic bacteria in the heavy metal (Cu2+ and Zn2+) treatment group was 2-10 times higher than that in the control. Moreover, heavy metals (Cu2+ and Zn2+) significantly increased the horizontal transfer of plasmids in pathogenic bacteria. Of particular interest is that heavy metals facilitated the horizontal transfer of conjugative plasmids, which may lead to the prevalence of multidrug-resistant pathogenic bacteria in the Xiangjiang River.

Prospect of Spin-Orbitronic Devices and Their Applications.

Science, engineering, and medicine ultimately demand fast information processing with ultra-low power consumption. The recently developed spin-orbit torque (SOT)-induced magnetization switching paradigm has been fueling opportunities for spin-orbitronic devices, i.e., enabling SOT memory and logic devices at sub-nano second and sub-picojoule regimes. Importantly, spin-orbitronic devices are intrinsic of nonvolatility, anti-radiation, unlimited endurance, excellent stability, and CMOS compatibility, toward emerging applications, e.g., processing in-memory, neuromorphic computing, probabilistic computing, and 3D magnetic random access memory. Nevertheless, the cutting-edge SOT-based devices and application remain at a premature stage owing to the lack of scalable methodology on the field-free SOT switching. Moreover, spin-orbitronics poises as an interdisciplinary field to be driven by goals of both fundamental discoveries and application innovations, to open fascinating new paths for basic research and new line of technologies. In this perspective, the specific challenges and opportunities are summarized to exert momentum on both research and eventual applications of spin-orbitronic devices.

Colonization of Mice With Amoxicillin-Associated Klebsiella variicola Drives Inflammation via Th1 Induction and Treg Inhibition.

ß-Lactam antibiotics can increase the resistance and virulence of individual intestinal microorganisms, which may affect host physiology and health. Klebsiella, a crucial gut inhabitant, has been confirmed to be resistant to most ß-lactam antibiotics and contributes to the etiology of inflammatory bowel disease (IBD). In this study, the influence of amoxicillin (AMO) on Klebsiella and its role in colitis was investigated in an antibiotic cocktail (ABx) murine model. The results suggested that a 7-day AMO treatment significantly enriched the abundance of Klebsiella and enhanced serum resistance, antibiotic resistance, and biofilm formation ability of Klebsiella variicola (K. variicola) compared to the wild-type strain in the control group mice. Colonization of mice with the AMO-associated K. variicola could induce Th1 cells and inhibit Treg differentiation to promote inflammation in ABx murine model. In addition, inoculation of AMO-associated K. variicola in dextran sodium sulfate (DSS)-induced colitis murine model mice also confirmed that K. variicola colonization exacerbated inflammation as assessed by increased TNF-α, IFN-γ, IL-17a, and disease activity (DAI) levels; decreased colon length and bodyweight; and a disrupted Th1/Treg balance. The results of our study demonstrate that AMO enhances Klebsiella virulence in mice by disrupting the T cell equilibrium to exacerbate colitis, thereby providing a reference for proper antibiotic prescription.

The Zscan4-Tet2 Transcription Nexus Regulates Metabolic Rewiring and Enhances Proteostasis to Promote Reprogramming.

Evolutionarily conserved SCAN (named after SRE-ZBP, CTfin51, AW-1, and Number 18 cDNA)-domain-containing zinc finger transcription factors (ZSCAN) have been found in both mouse and human genomes. Zscan4 is transiently expressed during zygotic genome activation (ZGA) in preimplantation embryos and induced pluripotent stem cell (iPSC) reprogramming. However, little is known about the mechanism of Zscan4 underlying these processes of cell fate control. Here, we show that Zscan4f, a representative of ZSCAN proteins, is able to recruit Tet2 through its SCAN domain. The Zscan4f-Tet2 interaction promotes DNA demethylation and regulates the expression of target genes, particularly those encoding glycolytic enzymes and proteasome subunits. Zscan4f regulates metabolic rewiring, enhances proteasome function, and ultimately promotes iPSC generation. These results identify Zscan4f as an important partner of Tet2 in regulating target genes and promoting iPSC generation and suggest a possible and common mechanism shared by SCAN family transcription factors to recruit ten-eleven translocation (TET) DNA dioxygenases to regulate diverse cellular processes, including reprogramming.

Amoxicillin Increased Functional Pathway Genes and Beta-Lactam Resistance Genes by Pathogens Bloomed in Intestinal Microbiota Using a Simulator of the Human Intestinal Microbial Ecosystem.

Antibiotics are frequently used to treat bacterial infections; however, they affect not only the target pathogen but also commensal gut bacteria. They may cause the dysbiosis of human intestinal microbiota and consequent metabolic alterations, as well as the spreading of antibiotic resistant bacteria and antibiotic resistance genes (ARGs). In vitro experiments by simulator of the human intestinal microbial ecosystem (SHIME) can clarify the direct effects of antibiotics on different regions of the human intestinal microbiota, allowing complex human microbiota to be stably maintained in the absence of host cells. However, there are very few articles added the antibiotics into this in vitro model to observe the effects of antibiotics on the human intestinal microbiota. To date, no studies have focused on the correlations between the bloomed pathogens caused by amoxicillin (AMX) exposure and increased functional pathway genes as well as ARGs. This study investigated the influence of 600 mg day-1 AMX on human intestinal microbiota using SHIME. The impact of AMX on the composition and function of the human intestinal microbiota was revealed by 16S rRNA gene sequencing and high-throughput quantitative PCR. The results suggested that: (i) AMX treatment has tremendous influence on the overall taxonomic composition of the gut microbiota by increasing the relative abundance of Klebsiella [linear discriminant analysis (LDA) score = 5.26] and Bacteroides uniformis (LDA score = 4.75), as well as taxonomic diversity (Simpson, P = 0.067, T-test; Shannon, P = 0.061, T-test), and decreasing the members of Parabacteroides (LDA score = 4.18), Bifidobacterium (LDA score = 4.06), and Phascolarctobacterium (LDA score = 3.95); (ii) AMX exposure significantly enhanced the functional pathway genes and beta-lactam resistance genes, and the bloomed pathogens were strongly correlated with the metabolic and immune system diseases gene numbers (R = 0.98, P < 0.001) or bl2_len and bl2be_shv2 abundance (R = 0.94, P < 0.001); (iii) the changes caused by AMX were "SHIME-compartment" different with more significant alteration in ascending colon, and the effects were permanent, which could not be restored after 2-week AMX discontinuance. Overall results demonstrated negative side-effects of AMX, which should be considered for AMX prescription.