Double-negative T cells ameliorate psoriasis by selectively inhibiting IL-17A-producing γδlow T cells.

BACKGROUND: Psoriasis is a chronic immune-mediated skin condition. Although biologic treatments are effective in controlling psoriasis, some patients do not respond or lose response to these therapies. Thus, new strategies for psoriasis treatment are still urgently needed. Double-negative T cells (DNT) play a significant immunoregulatory role in autoimmune diseases. In this study, we aimed to evaluate the protective effect of DNT in psoriasis and explore the underlying mechanism. METHODS: We conducted a single adoptive transfer of DNT into an imiquimod (IMQ)-induced psoriasis mouse model through tail vein injection. The skin inflammation and IL-17A producing γδ T cells were evaluated. RESULTS: DNT administration significantly reduced the inflammatory response in mouse skin, characterized by decreased skin folds, scales, and red patches. After DNT treatment, the secretion of IL-17A by RORc+ γδlow T cells in the skin was selectively suppressed, resulting in an amelioration of skin inflammation. Transcriptomic data suggested heightened expression of NKG2D ligands in γδlow T cells within the mouse model of psoriasis induced by IMQ. When blocking the NKG2D ligand and NKG2D (expressed by DNT) interaction, the cytotoxic efficacy of DNT against RORc+IL17A+ γδlow T cells was attenuated. Using Ccr5-/- DNT for treatment yielded evidence that DNT migrates into inflamed skin tissue and fails to protect IMQ-induced skin lesions. CONCLUSIONS: DNT could migrate to inflamed skin tissue through CCR5, selectively inhibit IL-17-producing γδlow T cells and finally ameliorate mouse psoriasis. Our study provides feasibility for using immune cell therapy for the prevention and treatment of psoriasis in the clinic.

Unearthing a novel function of SRSF1 in binding and unfolding of RNA G-quadruplexes.

SRSF1 governs splicing of over 1500 mRNA transcripts. SRSF1 contains two RNA-recognition motifs (RRMs) and a C-terminal Arg/Ser-rich region (RS). It has been thought that SRSF1 RRMs exclusively recognize single-stranded exonic splicing enhancers, while RS lacks RNA-binding specificity. With our success in solving the insolubility problem of SRSF1, we can explore the unknown RNA-binding landscape of SRSF1. We find that SRSF1 RS prefers purine over pyrimidine. Moreover, SRSF1 binds to the G-quadruplex (GQ) from the ARPC2 mRNA, with both RRMs and RS being crucial. Our binding assays show that the traditional RNA-binding sites on the RRM tandem and the Arg in RS are responsible for GQ binding. Interestingly, our FRET and circular dichroism data reveal that SRSF1 unfolds the ARPC2 GQ, with RS leading unfolding and RRMs aiding. Our saturation transfer difference NMR results discover that Arg residues in SRSF1 RS interact with the guanine base but not other nucleobases, underscoring the uniqueness of the Arg/guanine interaction. Our luciferase assays confirm that SRSF1 can alleviate the inhibitory effect of GQ on gene expression in the cell. Given the prevalence of RNA GQ and SR proteins, our findings unveil unexplored SR protein functions with broad implications in RNA splicing and translation.

Revolutionizing energy practices: Unleashing the power of artificial intelligence in corporate energy transition.

Corporate energy transition is crucial for long-term sustainable development. The widely discussed Artificial Intelligence (AI), as a disruptive technological innovation, is highly potential for enhancing environment performance. However, the specific impact of AI on the process of corporate energy transition and its underlying mechanisms have not been fully explored. This study focuses on A-share listed corporates in Shanghai and Shenzhen stock markets in China spanning from 2011 to 2021. Based on corporate annual report information and information from over 200,000 patent application texts, we innovatively construct indicators for corporate energy transition and AI technology application. Furthermore, we empirically investigate the impact of AI technology on corporate energy transition and its potential mechanisms through combining information asymmetry theory and institutional theory. The empirical results indicate that: 1) AI can drive corporate energy transition and the promoting effect of AI collaborative innovation on corporate energy transition should not be ignored. 2) AI can help corporates achieve energy transition through pathways such as mitigating information asymmetry, reducing financing constraints, adjusting sustainable development concepts and practices. 3) The driving effect of AI on corporate energy transition varies depending on the characteristics of different types of corporates, industries, and regions. This study provides strategic guidance and decision support for business managers and policymakers, assisting both corporates and governments in better utilizing AI technology during the social energy transition process to achieve a dual optimization of environmental and economic goals.

Hybrid supervised and reinforcement learning for the design and optimization of nanophotonic structures.

From higher computational efficiency to enabling the discovery of novel and complex structures, deep learning has emerged as a powerful framework for the design and optimization of nanophotonic circuits and components. However, both data-driven and exploration-based machine learning strategies have limitations in their effectiveness for nanophotonic inverse design. Supervised machine learning approaches require large quantities of training data to produce high-performance models and have difficulty generalizing beyond training data given the complexity of the design space. Unsupervised and reinforcement learning-based approaches on the other hand can have very lengthy training or optimization times associated with them. Here we demonstrate a hybrid supervised learning and reinforcement learning approach to the inverse design of nanophotonic structures and show this approach can reduce training data dependence, improve the generalizability of model predictions, and significantly shorten exploratory training times. The presented strategy thus addresses several contemporary deep learning-based challenges, while opening the door for new design methodologies that leverage multiple classes of machine learning algorithms to produce more effective and practical solutions for photonic design.

Effect of mitochondrial calcium homeostasis-mediated endogenous enzyme activation on tenderness of beef muscle based on MCU modulators.

The mitochondrial calcium uniporter (MCU) occupies a noteworthy position in the regulation of mitochondrial calcium uptake. This study investigated the effects of MCU modulator-mediated mitochondrial calcium on mitochondrial dysfunction, oxidative stress, endogenous enzyme activities, and tenderness during postmortem aging. Spermine, as an activator of MCU, resulted in an increase in mitochondrial calcium levels, not only disrupting mitochondrial morphology but also triggering mitochondrial oxidative stress and downregulation of antioxidant factors. Additionally, the spermine group underwent later activation of calpain and earlier activation of caspases, as well as the myofibril fragmentation index was initially lower and then higher compared with control group, indicating that endogenous enzymes played an indispensable role in different aging periods. Interestingly, the results of the Ru360 (an inhibitor of MCU) group were opposite to those aforementioned findings. Our data provide a novel perspective on the regulatory mechanism of mitochondrial calcium homeostasis mediated by MCU on tenderness.

Research progress on chitosan and its derivatives in the fields of corrosion inhibition and antimicrobial activity.

Chitosan stands out as the only known polysaccharide of its kind, second only to cellulose. As the second-largest biopolymer globally, chitosan and its derivatives are extensively used in diverse areas such as metal anti-corrosion prevention, food production, and medical fields. Its benefits include environmental friendliness, non-toxicity, cost-effectiveness, and biodegradability. Notably, the use of chitosan and its derivatives has gained substantial attention and has been extensively researched in the fields of metal anti-corrosion prevention and antibacterial applications. By means of chemical modification or synergistic action, the inherent limitations of chitosan can be substantially improved, thereby enhancing its biological and physicochemical properties to meet a wider range of applications and more demanding application requirements. This article offers a comprehensive review of chitosan and its modified composite materials, focusing on the enhancement of their anticorrosion and antibacterial properties, as well as the mechanisms by which they serve as anticorrosion and antibacterial agents. Additionally, it summarizes the synthesis routes of various modification methods of chitosan and their applications in different fields, aiming to contribute to the interdisciplinary development and potential applications of chitosan in various areas.

Purification of SRSF1 from E. coli for Biophysical and Biochemical Assays.

The Ser/Arg-rich splicing factors (SR proteins) constitute a crucial protein family in alternative splicing, comprising twelve members characterized by unique repetitive Arg-Ser dipeptide sequences (RS) and one to two RNA-recognition motifs (RRM). The RS regions of SR proteins undergo variable phosphorylation, resulting in unphosphorylated, partially phosphorylated, or hyper-phosphorylated states based on functional requirements. Despite the identification of the SR protein family over 30 years ago, the purification of native SR proteins in soluble form at large quantities has presented challenges due to their low solubility. This protocol delineates a method for acquiring soluble, full-length, unphosphorylated, hypo- and hyper-phosphorylated SRSF1, a prototypical SR family member. Notably, this protocol facilitates the purification of SRSF1 in ample quantities suitable for NMR, as well as various biophysical and biochemical studies. The methodologies and principles outlined herein are expected to extend beyond SRSF1 protein production and can be adapted for purifying other SR protein family members or SR-related proteins, such as snRNP70 and U2AF-35. Given the involvement of these proteins in numerous essential biological processes, this protocol will prove beneficial to researchers in related fields. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Purification of SRSF1 from E. coli Support Protocol: Purification of ULP1 Basic Protocol 2: Purification of hypo-phosphorylated SRSF1 from E. coli Basic Protocol 3: Purification of hyper-phosphorylated SRSF1 from E. coli.

Ginsenoside Rg3 decreases breast cancer stem-like phenotypes through impairing MYC mRNA stability.

Breast cancer stem cells (BCSCs) are responsible for breast cancer metastasis, recurrence and treatment resistance, all of which make BCSCs potential drivers of breast cancer aggression. Ginsenoside Rg3, a traditional Chinese herbal medicine, was reported to have multiple antitumor functions. Here, we revealed a novel effect of Rg3 on BCSCs. Rg3 inhibits breast cancer cell viability in a dose- and time-dependent manner. Importantly, Rg3 suppressed mammosphere formation, reduced the expression of stemness-related transcription factors, including c-Myc, Oct4, Sox2 and Lin28, and diminished ALDH(+) populations. Moreover, tumor-bearing mice treated with Rg3 exhibited robust delay of tumor growth and a decrease in tumor-initiating frequency. In addition, we found that Rg3 suppressed breast cancer stem-like properties mainly through inhibiting MYC expression. Mechanistically, Rg3 accelerated the degradation of MYC mRNA by enhancing the expression of the let-7 family, which was demonstrated to bind to the MYC 3' untranslated region (UTR). In conclusion, our findings reveal the remarkable suppressive effect of Rg3 on BCSCs, suggesting that Rg3 is a promising therapeutic treatment for breast cancer.

The role of fat content in coconut milk: Stability and digestive properties.

The fat in coconut milk contributes to unique flavour, while increasing fat content affects stability of the coconut milk. In this study, coconut water and fat were separated, recombined, and homogenized to obtain coconut milk with different fat contents (0-20 %). Emulsifying properties, stability, and digestibility of coconut milk with different fat contents were comprehensively evaluated. The results showed that as the fat content increased from 0 to 20 %, the droplet size increased from 2.18 to 4.70 µm and the viscosity showed an increasing trend. During storage and freeze-thaw, coconut milk with 5 % and 10 % fat content showed excellent stability. In addition, coconut milk with 10 % fat content had superior fat digestibility, which was related to high affinity of pancrelipase. In short, this study revealed that fat content below 10 % can withstand environmental factors such as storage, lipid oxidation, and freeze-thaw, which can be accurately developed as coconut milk products.

Anthocyanin biosynthesis in goji berry is inactivated by deletion in a bHLH transcription factor LrLAN1b promoter.

Black goji berry (Lycium ruthenicum Murray) contains a rich source of health-promoting anthocyanins which are used in herbal medicine and nutraceutical foods in China. A natural variant producing white berries allowed us to identify two key genes involved in the regulation of anthocyanin biosynthesis in goji berries: one encoding a MYB transcription factor (LrAN2-like) and one encoding a basic helix-loop-helix (bHLH) transcription factor (LrAN1b). We previously found that LrAN1b expression was lost in the white berry variant, but the molecular basis for this phenotype was unknown. Here, we identified the molecular mechanism for loss of anthocyanins in white goji berries. In white goji, the LrAN1b promoter region has a 229-bp deletion that removes 3 MYB-binding elements and 1 bHLH-binding element, which are key to its expression. Complementation of the white goji berry LrAN1b allele with the LrAN1b promoter restored pigmentation. Virus-induced gene silencing of LrAN1b in black goji berry reduced fruit anthocyanin biosynthesis. Molecular analyses showed that LrAN2-like and another bHLH transcription factor LrJAF13 can activate LrAN1b by binding directly to the MYB-recognizing element (MRE) and bHLH-recognizing element (BRE) of its promoter-deletion region. LrAN1b expression is enhanced by the interaction of LrAN2-like with LrJAF13 and the WD40 protein LrAN11. LrAN2-like and LrAN11 interact with either LrJAF13 or LrAN1b to form two MYB-bHLH-WD40 (MBW) complexes, which hierarchically regulate anthocyanin biosynthesis in black goji berry. This study on a natural variant builds a comprehensive anthocyanin regulatory network that may be manipulated to tailor goji berry traits.

Polyelectrolyte modified black phosphorus/titania nanosheet heterojunction enhanced photocatalysis: Synergistic enhancement effect of interface affinity and electron transport channel.

The instability and high electron-hole recombination have limited the application of black phosphorus (BP) as an excellent photocatalyst. To address these challenges, poly dimethyl diallyl ammonium chloride (PDDA), poly (allylamine hydrochloride) (PAH), and polyethyleneimine (PEI) are introduced to the functionalization of BP (F-BP), which can not only enhance its stability, but also boost the carrier transfer. Furthermore, a high-performance heterojunction photocatalyst is fabricated using F-BP and titania nanosheets (TNs) via a layer-by-layer self-assembly approach. The experimental outcomes unequivocally indicate that F-BP exhibits fast charge migration compared to BP. The density functional theory (DFT), in situ Kelvin-probe force microscopy (KPFM) and other advanced characterization techniques collectively unfold that PDDA modified BP can notably boost separation and propagation of charges, along with an enhanced carrier abundance. In summary, this novel strategy of using polyelectrolytes to enhance the electron transfer and the stability of BP permits immense potential in building next-generation BP-based high efficiency photocatalysts.

Organophosphorus flame retardants in fish from the middle reaches of the Yangtze River: Tissue distribution, age-dependent accumulation and ecological risk assessment.

Two fish species from the middle reaches of the Yangtze River, China, were sampled to investigate the occurrence, tissue distribution, age-dependent accumulation and ecological risk assessment of 24 organophosphorus flame retardants (OPFRs). Seventeen OPFRs were detected in tissue samples with a total concentration ranging from not detected (ND) to 1092 ng g-1 dw. Cl-OPFRs were predominant in all tissues (mean: 145 ng g-1 dw, median: 72.9 ng g-1 dw) and the concentrations of OPFRs in brain were the greatest (crucian carp: 525 ng g-1 dw, silver carp: 56.0 ng g-1 dw) compared with the other three organs (e.g., liver, muscle and gonad). Furthermore, the total concentrations of OPFRs in crucian carp tissues were significantly greater than those in silver carp (P < 0.01). Age-dependent accumulation of OPFRs was observed in the two fish species, but the accumulation profiles in the two fish species were different. Ecological risk assessment demonstrated that both fish species were at medium to high risk, and TDCIPP was a main contributor (>50%).

Lipid Metabolic Disorders Induced by Organophosphate Esters in Silver Carp from the Middle Reaches of the Yangtze River.

The Yangtze River fishery resources have declined strongly over the past few decades. One suspected reason for the decline in fishery productivity, including silver carp (Hypophthalmichthys molitrix), has been linked to organophosphate esters (OPEs) contaminant exposure. In this study, the adverse effect of OPEs on lipid metabolism in silver carp captured from the Yangtze River was examined, and our results indicated that muscle concentrations of the OPEs were positively associated with serum cholesterol and total lipid levels. In vivo laboratory results revealed that exposure to environmental concentrations of OPEs significantly increased the concentrations of triglyceride, cholesterol, and total lipid levels. Lipidome analysis further confirmed the lipid metabolism dysfunction induced by OPEs, and glycerophospholipids and sphingolipids were the most affected lipids. Hepatic transcriptomic analysis found that OPEs caused significant alterations in the transcription of genes involved in lipid metabolism. Pathways associated with lipid homeostasis, including the peroxisome proliferator-activated receptor (PPAR) signal pathway, cholesterol metabolism, fatty acid biosynthesis, and steroid biosynthesis, were significantly changed. Furthermore, the affinities of OPEs were different, but the 11 OPEs tested could bind with PPARγ, suggesting that OPEs could disrupt lipid metabolism by interacting with PPARγ. Overall, this study highlighted the harmful effects of OPEs on wild fish and provided mechanistic insights into OPE-induced metabolic disorders.

First-principles study of high-pressure structural phase transition and superconductivity of YBeH8.

The theory-led prediction of LaBeH8, which has a high superconducting critical temperature (Tc) above liquid nitrogen under a pressure level below 1 Mbar, has been experimentally confirmed. YBeH8, which has a structural configuration similar to that of LaBeH8, has also been predicted to be a high-temperature superconductor at high pressure. In this study, we focus on the structural phase transition and superconductivity of YBeH8 under pressure by using first-principles calculations. Except for the known face-centered cubic phase of Fm3̄m, we found a monoclinic phase with P1̄ symmetry. Moreover, the P1̄ phase transforms to the Fm3̄m phase at ∼200 GPa with zero-point energy corrections. Interestingly, the P1̄ phase undergoes a complex electronic phase transition from semiconductor to metal and then to superconducting states with a low Tc of 40 K at 200 GPa. The Fm3̄m phase exhibits a high Tc of 201 K at 200 GPa, and its Tc does not change significantly with pressure. When we combine the method using two coupling constants, λopt and λac, with first-principles calculations, λopt is mainly supplied by the Be-H alloy backbone, which accounts for about 85% of total λ and makes the greatest contribution to the high Tc. These insights not only contribute to a deeper understanding of the superconducting behavior of this ternary hydride but may also guide the experimental synthesis of hydrogen-rich compounds.

Regional delivery of mesothelin-targeted chimeric antigen receptor T-cell effectively and safely targets colorectal cancer liver metastases in mice.

Background: Liver metastasis is the major cause of colorectal cancer related death. Mesothelin (MSLN)-targeted chimeric antigen receptor (CAR) T-cell therapy has been illustrated effective and safe through regional delivery of breast cancer, ovarian cancer and malignant mesothelioma tumors. Herein, we investigated the safety, efficacy, and immune microenvironment of regional delivery of MSLN (CAR) T-cell in the treatment of colorectal carcinoma liver metastases (CRLM). Methods: Second-generation MSLN CAR T-cells were administered by portal vein (PV) or caudal vein (CV, systemic administration) delivery in an orthotopic MSLN+ CRLM nonobese diabetic (NOD)/severe combined immunodeficient (SCID)/γc-/- (NSG) mouse model. A total of 20 mice were randomly divided into control group, non-transduced T cell (NT)-CV group, NT-PV group, MSLN CAR T-cell CV (MSLN-CV) group, and MSLN CAR T-cell PV (MSLN-PV) group, with each group containing four mice to examine the safety and efficacy. The bioluminescence intensity (BLI) of tumor burden, tumor tissue macroscopic and microscopic observation were used to evaluate treatment efficacy. The safety was examined by body weight, survival time, and vital organ damage of mice. CAR T-cell infiltration and cytokine concentration were analyzed by flow cytometry, and immunostaining. The change of immune microenvironment between regional delivery and systemic delivery was investigated on an immune reconstructed CRLM patient-derived xenograft (PDX) model. Additionally, T cell subsets and immunosuppressive markers were examined. Results: PV administration of 1×107/100 µL MSLN CAR T-cells in 20 NSG mice was well tolerated, and no overt toxicity was observed. The tumor burden in the PV group was obviously alleviated. The BLI was (0.73±0.52)×109 in PV group and (1.97±0.11)×109 in CV group (P<0.05), CD8+ granzyme B (GB)+ T cell percentage (MSLN-CV 4.42%±0.47% vs. MSLN-PV 13.5%±4.67%, P<0.01) and cytokine concentration were obviously increased in the MSLN-PV group. In the immune reconstituted CRLM PDX model, intratumor (IT) delivery of MSLN CAR T-cells exhibited much more infiltration of CD4+ and CD8+ T cells accompanied with elevated expression levels of PD-1, LAG-3, and TIM-3. Conclusions: Regional delivery of MSLN-targeted CAR T-cell therapy has encouraging results in the orthotopic CRLM NSG mouse model and PDX model, and converts the tumor microenvironment from cold to hot. This study may provide a new therapeutic approach for CRLM. Further clinical study is needed.

Apoptosis and pyroptosis in the nasal mucosa of Syrian hamster during SARS-CoV-2 infection and reinfection.

In SARS-CoV-2 infection, it has been observed that viral replication lasts longer in the nasal mucosa than in the lungs, despite the presence of a high viral load at both sites. In hamsters, we found that the nasal mucosa exhibited a mild inflammatory response and minimal pathological injuries, whereas the lungs displayed a significant inflammatory response and severe injuries. The underlying cellular events may be induced by viral infection in three types of cell death: apoptosis, pyroptosis, and necroptosis. Our findings indicate that apoptosis was consistently activated during infection in the nasal mucosa, and the levels of apoptosis were consistent with the viral load. On the other hand, pyroptosis and a few instances of necroptosis were observed only on 7 dpi in the nasal mucosa. In the lungs, however, both pyroptosis and apoptosis were prominently activated on 3 dpi, with lower levels of apoptosis compared to the nasal mucosa. Interestingly, in reinfection, obvious viral load and apoptosis in the nasal mucosa were detected on 3 dpi, while no other forms of cell death were detected. We noted that the inflammatory reactions and pathological injuries in the nasal mucosa were milder, indicating that apoptosis may play a role in promoting lower inflammatory reactions and milder pathological injuries and contribute to the generation of long-term viral replication in the nasal mucosa. Our study provides valuable insights into the differences in cellular mechanisms during SARS-CoV-2 infection and highlights the potential significance of apoptosis regulation in the respiratory mucosa for controlling viral replication.

Intrinsic Defect-Driven Synergistic Synaptic Heterostructures for Gate-Free Neuromorphic Phototransistors.

The optoelectronic synaptic devices based on two-dimensional (2D) materials offer great advances for future neuromorphic visual systems with dramatically improved integration density and power efficiency. The effective charge capture and retention are considered as one vital prerequisite to realizing the synaptic memory function. However, the current 2D synaptic devices are predominantly relied on materials with artificially-engineered defects or intricate gate-controlled architectures to realize the charge trapping process. These approaches, unfortunately, suffer from the degradation of pristine materials, rapid device failure, and unnecessary complication of device structures. To address these challenges, an innovative gate-free heterostructure paradigm is introduced herein. The heterostructure presents a distinctive dome-like morphology wherein a defect-rich Fe7 S8 core is enveloped snugly by a curved MoS2 dome shell (Fe7 S8 @MoS2 ), allowing the realization of effective photocarrier trapping through the intrinsic defects in the adjacent Fe7 S8 core. The resultant neuromorphic devices exhibit remarkable light-tunable synaptic behaviors with memory time up to ≈800 s under single optical pulse, thus demonstrating great advances in simulating visual recognition system with significantly improved image recognition efficiency. The emergence of such heterostructures foreshadows a promising trajectory for underpinning future synaptic devices, catalyzing the realization of high-efficiency and intricate visual processing applications.

Biodiversity conservation and management of lake wetlands based on the spatiotemporal evolution patterns of crane habitats.

The typical lake wetlands in the middle and lower reaches of the Yangtze River are important wintering sites of cranes in China. The spatiotemporal evolution of crane populations and their habitats has great value in clarifying the pivotal role of regional lake wetlands in biodiversity conservation. Therefore, 2562 data points of four crane species were selected in this study. The data reflected the distributional position of the cranes over the period 2000-2020. Twelve surrounding environmental factors were selected to investigate the spatiotemporal evolution in the study area by using the MaxEnt model. The Jackknife method was used to identify the main environmental factors affecting the choice of crane habitats. The results indicated that: (1) Developed land in the study area increased by 42,795.81 hm2. The crane populations were mainly distributed in the farmland and mudflat, and their number decreased yearly. (2) From 2000 to 2020, the area of suitable crane habitat experienced an overall decrease. Specifically, the mid-suitable area dwindled by 6234.23 hm2, marking a substantial reduction of 52.05 %. Similarly, the most suitable area saw a decline of 786.41 hm2, representing a noteworthy decrease of 71.09 %. (3) The findings from the analysis of influencing factors revealed a dynamic pattern over the years. Habitat type, water density, and distance to water were the main influencing factors in the study area from 2000 to 2020. This study provides a new perspective on the conservation and structural habitat restoration of crane populations in the middle and lower reaches of the Yangtze River.

Mechanisms Underlying the Overlooked Chiral Fungicide-Driven Enantioselective Proliferation of Antibiotic Resistance in Earthworm Intestinal Microbiome.

From a "One Health" perspective, the global threat of antibiotic resistance genes (ARGs) is associated with modern agriculture practices including agrochemicals application. Chiral fungicides account for a considerable proportion of wildly used agrochemicals; however, whether and how their enantiomers lead to differential proliferation of antibiotic resistance in agricultural environments remain overlooked. Focused on the soil-earthworm ecosystem, we for the first time deciphered the mechanisms underlying the enantioselective proliferation of antibiotic resistance driven by the enantiomers of a typical chiral fungicide mandipropamid (i.e., R-MDP and S-MDP) utilizing a multiomic approach. Time-series metagenomic analysis revealed that R-MDP led to a significant enhancement of ARGs with potential mobility (particularly the plasmid-borne ARGs) in the earthworm intestinal microbiome. We further demonstrated that R-MDP induced a concentration-dependent facilitation of plasmid-mediated ARG transfer among microbes. In addition, transcriptomic analysis with verification identified the key aspects involved, where R-MDP enhanced cell membrane permeability, transfer ability, biofilm formation and quorum sensing, rebalanced energy production, and decreased cell mobility versus S-MDP. Overall, the findings provide novel insights into the enantioselective disruption of microbiome and resistome in earthworm gut by chiral fungicides and offer significant contributions to the comprehensive risk assessment of chiral agrochemicals in agroecosystems.