In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions.

Functional genomic screens in two-dimensional cell culture models are limited in identifying therapeutic targets that influence the tumor microenvironment. By comparing targeted CRISPR-Cas9 screens in a two-dimensional culture with xenografts derived from the same cell line, we identified MEN1 as the top hit that confers differential dropout effects in vitro and in vivo. MEN1 knockout in multiple solid cancer types does not impact cell proliferation in vitro but significantly promotes or inhibits tumor growth in immunodeficient or immunocompetent mice, respectively. Mechanistically, MEN1 knockout redistributes MLL1 chromatin occupancy, increasing H3K4me3 at repetitive genomic regions, activating double-stranded RNA expression and increasing neutrophil and CD8+ T cell infiltration in immunodeficient and immunocompetent mice, respectively. Pharmacological inhibition of the menin-MLL interaction reduces tumor growth in a CD8+ T cell-dependent manner. These findings reveal tumor microenvironment-dependent oncogenic and tumor-suppressive functions of MEN1 and provide a rationale for targeting MEN1 in solid cancers.

Integration of Hydrogels and 3D Bioprinting Technologies for Chronic Wound Healing Management.

The integration of hydrogel-based bioinks with 3D bioprinting technologies presents an innovative approach to chronic wound management, which is particularly challenging to treat because of its multifactorial nature and high risk of complications. Using precise deposition techniques, 3D bioprinting significantly alters traditional wound care paradigms by enabling the fabrication of patient-specific wound dressings that imitate natural tissue properties. Hydrogels are notably beneficial for these applications because of their abundant water content and mechanical properties, which promote cell viability and pathophysiological processes of wound healing, such as re-epithelialization and angiogenesis. This article reviews key 3D printing technologies and their significance in enhancing the structural and functional outcomes of wound-care solutions. Challenges in bioink viscosity, cell viability, and printability are addressed, along with discussions on the cross-linking and mechanical stability of the constructs. The potential of 3D bioprinting to revolutionize chronic wound management rests on its capacity to generate remedies that expedite healing and minimize infection risks. Nevertheless, further studies and clinical trials are necessary to advance these therapies from laboratory to clinical use.

Unveiling the unknown viral world in groundwater.

Viruses as the prevailing biological entities are poorly understood in underground realms. Here, we establish the first metagenomic Groundwater Virome Catalogue (GWVC) comprising 280,420 viral species ( ≥ 5 kb) detected from 607 monitored wells in seven geo-environmental zones throughout China. In expanding ~10-fold the global portfolio of known groundwater viruses, we uncover over 99% novel viruses and about 95% novel viral clusters. By linking viruses to hosts from 119 prokaryotic phyla, we double the number of microbial phyla known to be virus-infected in groundwater. As keystone ultrasmall symbionts in aquifers, CPR bacteria and DPANN archaea are susceptible to virulent viruses. Certain complete CPR viruses even likely infect non-CPR bacteria, while partial CPR/DPANN viruses harbor cell-surface modification genes that assist symbiont cell adhesion to free-living microbes. This study reveals the unknown viral world and auxiliary metabolism associated with methane, nitrogen, sulfur, and phosphorus cycling in groundwater, and highlights the importance of subsurface virosphere in viral ecology.

High-Performance Intrinsically Stretchable Organic Photovoltaics Enabled by Robust Silver Nanowires/S-PH1000 Hybrid Transparent Electrodes.

Intrinsically stretchable organic photovoltaics (is-OPVs) hold significant promise for integration into self-powered wearable electronics. However, their potential is hindered by the lack of sufficient consistency between optoelectronic and mechanical properties. This is primarily due to the limited availability of stretchable transparent electrodes (STEs) that possess both high conductivity and stretchability. Here, a hybrid STE with exceptional conductivity, stretchability, and thermal stability is presented. Specifically, STEs are composed of the modified PH1000 (referred to as S-PH1000) and silver nanowires (AgNWs). The S-PH1000 endows the STE with good stretchability and smoothens the surface, while the AgNWs enhance the charge transport. The resulting hybrid STEs enable is-OPVs to a remarkable power conversion efficiency (PCE) of 16.32%, positioning them among the top-performing is-OPVs. With 10% elastomer, the devices retain 82% of the initial PCE after 500 cycles at 20% strain. Additionally, OPVs equipped with these STEs exhibit superior thermal stability compared to those using indium tin oxide electrodes, maintaining 75% of the initial PCE after annealing at 85 °C for 390 h. The findings underscore the suitability of the designed hybrid electrodes for efficient and stable is-OPVs, offering a promising avenue for the future application of OPVs.

A novel pelvis-prostate model BPPP predicts immediate urinary continence after Retzius-sparing robotic-assisted laparoscopic radical prostatectomy.

This study aimed to construct a novel pelvis-prostate model BPPP which consists of body mass index (BMI), prostate volume (PV), pelvic cavity index (PCI) and prostate-muscle index (PMI) to predict the immediate urinary continence after Retzius-sparing robot assisted laparoscopic radical prostatectomy (RS-RARP). The perioperative data of patients with prostate cancer who underwent RS-RARP in the department of urology of Nanjing Drum Tower Hospital from June 2018 to June 2022 were retrospectively analyzed. 280 patients were eligible for this study in total. Multivariate analysis showed that BMI, PV, PCI, PMI and NVB preservation were significantly associated with immediate urinary continence after RS-RARP. Subgroup analysis showed that patients with low BMI, low PV, high PCI and high PMI had a higher recovery rate of immediate urinary continence. The area under the curve of BPPP (BMI + PV + PCI + PMI) for predicting the immediate recovery of urinary continence after RS-RARP was 0.726. Delong test showed that the area under the curve of the combined test for predicting the immediate urinary continence after RS-RARP was better compared with single parameter (p < 0.05). In conclusion the novel pelvis-prostate model BPPP may predict the immediate urinary continence after RS-RARP, providing information for preoperative decision-making.

Trans-rectovesical pouch urethral-sparing robotic-assisted simple prostatectomy: A case series.

Objective: To detail a novel technique of robotic-assisted simple prostatectomy that makes handling the gland protruding into the bladder neck easier and can preserve the urethra and retain ejaculation function as much as possible. Patients and methods: This is a prospective case series. Clinical data of 17 male patients who had large volume (>80 mL) benign prostatic hyperplasia (BPH) were enrolled to undergo trans-rectovesical pouch urethral-sparing robotic-assisted simple prostatectomy (usRASP). We adopted the approach through the space between the bladder neck and seminal vesicle to perform a usRASP that can avoid the detrusor skirt and fibrous matrix area of the retropubic prostate. Between the transitional zone and the peripheral zone of the large prostate, the hyperplastic prostatic gland tissue can be enucleated under direct vision while preserving the prostatic urethra and retaining the ejaculatory duct and bladder neck intact. All preoperative, perioperative and postoperative clinical data were collected, and descriptive analysis was performed. Results: The median intravesical prostatic protrusion was 19.3 mm (8.5-32.2). The median operative time was 100 min (75-140), and the median estimated blood loss was 100 mL (10-500). The median time to catheter removal was 7 days (5-7), with a median postoperative hospital stay of 2 days (2-4). After at least 6-month follow-up, the median maximum urine flow rate and postvoid residual volume were 40.1 mL/s (12.7-52.4) and 15 mL (5-23), respectively; the median International Prostate Symptom Score and Quality of Life score were 0 (0-6.3) and 1 (0-3), respectively; and the median total prostate-specific antigen was 0.84 ng/mL (0.15-1.01). All patients successfully underwent usRASP. Fifty-eight percent of patients with normal ejaculation function before surgery can still retain normal ejaculation function. Conclusion: We described a new approach to performing usRASP. This new method remarkably improved the voiding function, maintained antegrade ejaculation and did not increase the post-operative complications.

Engineering broad-spectrum resistance to rice bacterial blight by editing the OsETR susceptible haplotype using CRISPR/Cas9.

KEY MESSAGE: CRISPR/Cas9-mediated knockout of the susceptible haplotype of OsETR, encoding an embryogenesis transmembrane protein, confers broad-spectrum resistance to bacterial leaf blight in a susceptible rice cultivar without yield penalty.

Multi-omics illuminates the functional significance of previously unknown species in a full-scale landfill leachate treatment plant.

Landfill leachate treatment plants (LLTPs) harbor a vast reservoir of uncultured microbes, yet limited studies have systematically unraveled their functional potentials within LLTPs. Combining 36 metagenomic and 18 metatranscriptomic datasets from a full-scale LLTP, we unveiled a double-edged sword role of unknown species in leachate biotreatment and environmental implication. We identified 655 species-level genome bins (SGBs) spanning 47 bacterial and 3 archaeal phyla, with 75.9 % unassigned to any known species. Over 90 % of up-regulated functional genes in biotreatment units, compared to the leachate influent, were carried by unknown species and actively participated in carbon, nitrogen, and sulfur cycles. Approximately 79 % of the 37,366 carbohydrate active enzymes (CAZymes), with ∼90 % novelty and high expression, were encoded by unknown species, exhibiting great potential in biodegrading carbohydrate compounds linked to human meat-rich diets. Unknown species offered a valuable genetic resource of thousands of versatile, abundant, and actively expressed metabolic gene clusters (MGCs) and biosynthetic gene clusters (BGCs) for enhancing leachate treatment. However, unknown species may contribute to the emission of hazardous N2O/H2S and represented significant reservoirs for antibiotic-resistant pathogens that posed environmental safety risks. This study highlighted the significance of considering both positive and adverse effects of LLTP microbes to optimize LLTP performance.

Effects of maternal advanced lipoxidation end products diet on the glycolipid metabolism and gut microbiota in offspring mice.

Introduction: Dietary advanced lipoxidation end products (ALEs), which are abundant in heat-processed foods, could induce lipid metabolism disorders. However, limited studies have examined the relationship between maternal ALEs diet and offspring health. Methods: To investigate the transgenerational effects of ALEs, a cross-generation mouse model was developed. The C57BL/6J mice were fed with dietary ALEs during preconception, pregnancy and lactation. Then, the changes of glycolipid metabolism and gut microbiota of the offspring mice were analyzed. Results: Maternal ALEs diet not only affected the metabolic homeostasis of dams, but also induced hepatic glycolipid accumulation, abnormal liver function, and disturbance of metabolism parameters in offspring. Furthermore, maternal ALEs diet significantly upregulated the expression of TLR4, TRIF and TNF-α proteins through the AMPK/mTOR/PPARα signaling pathway, leading to dysfunctional glycolipid metabolism in offspring. In addition, 16S rRNA analysis showed that maternal ALEs diet was capable of altered microbiota composition of offspring, and increased the Firmicutes/Bacteroidetes ratio. Discussion: This study has for the first time demonstrated the transgenerational effects of maternal ALEs diet on the glycolipid metabolism and gut microbiota in offspring mice, and may help to better understand the adverse effects of dietary ALEs.

Eutrophication impacts the distribution and functional traits of viral communities in lakes.

Viruses play a crucial role in aquatic ecosystems by regulating microbial composition and impacting biogeochemical cycling. While the response of viral diversity to the trophic status has been preliminarily explored in lake ecosystems, there is limited integrated exploration of the biogeography of viruses, host associations, and the auxiliary metabolic genes (AMGs), particularly for plateau lakes. Therefore, this research investigated the viral biogeography, virus-host association, and AMGs in the surface waters of 11 lakes varying in trophic levels (eutrophic and oligo-mesotrophic) in the Yunnan-Guizhou plateau region of China. A total of 73,105 viral operational taxonomic units were obtained from 11 samples, with 84.8 % remaining unannotated at the family level, indicating a predominance of novel viruses within these lakes. The most abundant viral family was Kyanoviridae (24.4 %), recognized as a common cyanophage. The vast majority of cyanobacteria and several eukaryotic algae were predicted as hosts for the viruses, with a lytic lifestyle predominating the life strategy of these cyanophages, implying the potential influence of the virus on algae. The viral community structure significantly correlated with both trophic status and the bacterial community. The structure equation model analysis revealed chlorophyll a was the primary factor affecting viral communities. Moreover, numerous AMGs linked to carbon metabolism, phosphorus metabolism, sulfur metabolism, and photosynthesis were found in these lakes, some of which showed virus preference for the trophic statuses, suggesting a vital role of the virus in driving biogeochemical cycling in the lake crossing different nutrient levels. In addition, a restricted presence of viruses was found to infect humans or harbor antibiotic resistance genes in the lakes, suggesting a subtle yet potential link to human health. Overall, these findings offer insights into the response of viral communities to eutrophication and their potential role in biogeochemical cycling and controlling algal propagation.

Efficient and Flexible Method for Reducing Moderate-Size Deep Neural Networks with Condensation.

Neural networks have been extensively applied to a variety of tasks, achieving astounding results. Applying neural networks in the scientific field is an important research direction that is gaining increasing attention. In scientific applications, the scale of neural networks is generally moderate size, mainly to ensure the speed of inference during application. Additionally, comparing neural networks to traditional algorithms in scientific applications is inevitable. These applications often require rapid computations, making the reduction in neural network sizes increasingly important. Existing work has found that the powerful capabilities of neural networks are primarily due to their nonlinearity. Theoretical work has discovered that under strong nonlinearity, neurons in the same layer tend to behave similarly, a phenomenon known as condensation. Condensation offers an opportunity to reduce the scale of neural networks to a smaller subnetwork with a similar performance. In this article, we propose a condensation reduction method to verify the feasibility of this idea in practical problems, thereby validating existing theories. Our reduction method can currently be applied to both fully connected networks and convolutional networks, achieving positive results. In complex combustion acceleration tasks, we reduced the size of the neural network to 41.7% of its original scale while maintaining prediction accuracy. In the CIFAR10 image classification task, we reduced the network size to 11.5% of the original scale, still maintaining a satisfactory validation accuracy. Our method can be applied to most trained neural networks, reducing computational pressure and improving inference speed.

Comprehensive reutilization of Glycyrrhiza uralensis residue by extrusion-biological pretreatment for coproduction of flavonoids, cellulase, and ethanol.

A continuous chemical-free green approach was investigated for the comprehensive reutilization of all components in herbal extraction residues (HERs), taking Glycyrrhiza uralensis residue (GUR) as an example. The GUR structural changes induced by mechanical extrusion which improve the specific surface area and enzyme accessibility of GUR. With 3 % pretreated GUR loading of high-tolerance Penicillium oxalicum G2. The reducing sugar yield of 11.45 g/L was achieved, along with an 81.06 % in situ enzymatic hydrolysis. Finally, 8.23 g/L bioethanol (0.40 g/g total sugar) was produced from GUR hydrolysates after 24 h fermentation of Pichia stipitis G32. The amount of functional medicinal ingredients extracted from GUR after hydrolysis (39.63 mg/g) was 37.69 % greater than that of un-pretreated GUR. In total, 1.49 g flavonoids, 294.36 U cellulase, and 14.13 g ethanol could be produced from 100 g GUR using this process, illustrating that this green and efficient process has the potential for industrial production.

A review: targeting UBR5 domains to mediate emerging roles and mechanisms - chance or necessity?

Ubiquitinases are known to catalyze ubiquitin chains on target proteins to regulate various physiological functions like cell proliferation, autophagy, apoptosis, and cell cycle progression. As a member of E3 ligase, ubiquitin protein ligase E3 component n-recognin 5 (UBR5) belongs to the HECT E3 ligase and has been reported to be correlated with various pathophysiological processes. In this review, the authors give a comprehensive insight into the structure and function of UBR5. The authors discuss the specific domains of UBR5 and explore their biological functions separately. Furthermore, the authors describe the involvement of UBR5 in different pathophysiological conditions, including immune response, virus infection, DNA damage response, and protein quality control. Moreover, the authors provide a thorough summary of the important roles and regulatory mechanisms of UBR5 in cancers and other diseases. On the whole, investigating the domains and functions of UBR5, elucidating the underlying mechanisms of UBR5 with various substrates in detail may provide new theoretical basis for the treatment of diseases, including cancers, which could improve future studies to construct novel UBR5-targeted therapy strategies.

Prenatal and postnatal early life exposure to greenness and particulate matter of different size fractions in relation to childhood rhinitis - A multi-center study in China.

The impact of early life exposure to residential greenness on childhood rhinitis and its interaction with particulate matter (PM) of different size fractions remain inconsistent. Herein, we recruited 40,486 preschool children from randomly selected daycare centers in 7 cities in China from 2019 to 2020, and estimated exposure to residential greenness by the normalized difference vegetation index (NDVI) with a 500 m buffer. Exposure to ambient PM (PM1, PM2.5, and PM10) was evaluated using a satellite-based prediction model (daily, at a resolution of 1 km × 1 km). By mixed-effect logistic regression, NDVI values during pregnancy, in the first (0-1 year old) and the second (1-2 years old) year of life were negatively associated with lifetime rhinitis (LR) and current rhinitis (CR) (P < 0.001). PM in the same time windows was associated with increased risks of LR and CR in children, with smaller size fraction of PM showing greater associations. The negative associations between prenatal and postnatal NDVI and LR and CR in preschool children remained robust after adjusting for concomitant exposure to PM, whereas the associations of postnatal NDVI and rhinitis showed significant interactions with PM. At lower levels of PM, postnatal NDVI remained negatively associated with rhinitis and was partly mediated by PM (10.0-40.9 %), while at higher levels of PM, the negative associations disappeared or even turned positive. The cut-off levels of PM were identified for each size fraction of PM. In conclusion, prenatal exposure to greenness had robust impacts in lowering the risk of childhood rhinitis, while postnatal exposure to greenness depended on the co-exposure levels to PM. This study revealed the complex interplay of greenness and PM on rhinitis in children. The exposure time window in prenatal or postnatal period and postnatal concomitant PM levels played important roles in influencing the associations between greenness, PM and rhinitis.

Divergent Synthesis of Scabrolide A and Havellockate via an exo-exo-endo Radical Cascade.

Here we report a concise and divergent synthesis of scabrolide A and havellockate, representative members of polycyclic marine natural product furano(nor)cembranoids. The synthesis features a highly efficient exo-exo-endo radical cascade. Through the generation of two rings, three C-C bonds, and three contiguous stereocenters in one step, this remarkable transformation not only assembles the bowl-shaped, common 6-5-5 fused ring system from simple building blocks but also precisely installs the functionalities at desired positions and sets the stage for further divergent preparation of both target molecules. Further studies reveal that the robust and unusual 6-endo radical addition in the cascade is likely facilitated by the rigidity of the substrate.

On the role of asymmetric molecular geometry in high-performance organic solar cells.

Although asymmetric molecular design has been widely demonstrated effective for organic photovoltaics (OPVs), the correlation between asymmetric molecular geometry and their optoelectronic properties is still unclear. To access this issue, we have designed and synthesized several symmetric-asymmetric non-fullerene acceptors (NFAs) pairs with identical physical and optoelectronic properties. Interestingly, we found that the asymmetric NFAs universally exhibited increased open-circuit voltage compared to their symmetric counterparts, due to the reduced non-radiative charge recombination. From our molecular-dynamic simulations, the asymmetric NFA naturally exhibits more diverse molecular interaction patterns at the donor (D):acceptor (A) interface as compared to the symmetric ones, as well as higher D:A interfacial charge-transfer state energy. Moreover, it is observed that the asymmetric structure can effectively suppress triplet state formation. These advantages enable a best efficiency of 18.80%, which is one of the champion results among binary OPVs. Therefore, this work unambiguously demonstrates the unique advantage of asymmetric molecular geometry, unveils the underlying mechanism, and highlights the manipulation of D:A interface as an important consideration for future molecular design.

Uncertainty Quantification and Interpretability for Clinical Trial Approval Prediction.

Background: Clinical trial is a crucial step in the development of a new therapy (e.g., medication) and is remarkably expensive and time-consuming. Forecasting the approval of clinical trials accurately would enable us to circumvent trials destined to fail, thereby allowing us to allocate more resources to therapies with better chances. However, existing approval prediction algorithms did not quantify the uncertainty and provide interpretability, limiting their usage in real-world clinical trial management. Methods: This paper quantifies uncertainty and improves interpretability in clinical trial approval predictions. We devised a selective classification approach and integrated it with the Hierarchical Interaction Network, the state-of-the-art clinical trial prediction model. Selective classification, encompassing a spectrum of methods for uncertainty quantification, empowers the model to withhold decision-making in the face of samples marked by ambiguity or low confidence. This approach not only amplifies the accuracy of predictions for the instances it chooses to classify but also notably enhances the model's interpretability. Results: Comprehensive experiments demonstrate that incorporating uncertainty markedly enhances the model's performance. Specifically, the proposed method achieved 32.37%, 21.43%, and 13.27% relative improvement on area under the precision-recall curve over the base model (Hierarchical Interaction Network) in phase I, II, and III trial approval predictions, respectively. For phase III trials, our method reaches 0.9022 area under the precision-recall curve scores. In addition, we show a case study of interpretability that helps domain experts to understand model's outcome. The code is publicly available at https://github.com/Vincent-1125/Uncertainty-Quantification-on-Clinical-Trial-Outcome-Prediction. Conclusion: Our approach not only measures model uncertainty but also greatly improves interpretability and performance for clinical trial approval prediction.

Semaphorins in tumor microenvironment: Biological mechanisms and therapeutic progress.

Hallmark features of the tumor microenvironment include immune cells, stromal cells, blood vessels, and extracellular matrix (ECM), providing a conducive environment for the growth and survival of tumors. Recent advances in the understanding of cancer biology have highlighted the functional role of semaphorins (SEMAs). SEMAs are a large and diverse family of widely expressed secreted and membrane-binding proteins, which were initially implicated in axon guidance and neural development. However, it is now clear that they are widely expressed beyond the nervous system and participate in regulating immune responses and cancer progression. In fact, accumulating evidence disclosed that different SEMAs can either stimulate or restrict tumor progression, some of which act as important regulators of tumor angiogenesis. Conversely, limited information is known about the functional relevance of SEMA signals in TME. In this setting, we systematically elaborate the role SEMAs and their major receptors played in characterized components of TME. Furthermore, we provide a convergent view of current SEMAs pharmacological progress in clinical treatment and also put forward their potential application value and clinical prospects in the future.

Kidney function decline mediates the adverse effects of per- and poly-fluoroalkyl substances (PFAS) on uric acid levels and hyperuricemia risk.

Previous studies indicated per- and poly-fluoroalkyl substances (PFAS) were related to uric acid and hyperuricemia risk, but evidence for the exposure-response (E-R) curves and combined effect of PFAS mixture is limited. Moreover, the potential mediation effect of kidney function was not assessed. Hence, we conducted a national cross-sectional study involving 13,979 US adults in NHANES 2003-2018 to examine the associations of serum PFAS with uric acid and hyperuricemia risk, and the mediation effects of kidney function. Generalized linear models and E-R curves showed positive associations of individual PFAS with uric acid and hyperuricemia risk, and nearly linear E-R curves indicated no safe threshold for PFAS. Weighted quantile sum regression found positive associations of PFAS mixture with uric acid and hyperuricemia risk, and PFOA was the dominant contributor to the adverse effect of PFAS on uric acid and hyperuricemia risk. Causal mediation analysis indicated significant mediation effects of kidney function decline in the associations of PFAS with uric acid and hyperuricemia risk, with the mediated proportion ranging from 19 % to 57 %. Our findings suggested that PFAS, especially PFOA, may cause increased uric acid and hyperuricemia risk increase even at low levels, and kidney function decline plays a crucial mediation effect.

Shallow wet irrigation reduces nitrogen leaching loss rate in paddy fields by microbial regulation and lowers rate of downward migration of leaching water: a 15N-tracer study.

China consumes 35% of the world's fertilizer every year; however, most of the nitrogen fertilizers, which are essential for rice cultivation, are not used effectively. In this study, factors affecting the nitrogen leaching loss rate were studied in typical soil and rice varieties in South China. The effects of various irrigation measures on rice growth and nitrogen leaching loss were investigated by conducting experiments with eight groups. These groups included traditional irrigation (TI) and shallow wet irrigation (SWI). The TI is a common irrigation method for farmers in South China, maintaining a water layer of 5-8 cm depth. For SWI, after establishing a shallow water layer usually maintaining at 1-2 cm, paddy is irrigated when the field water level falls to a certain depth, then this process is then repeat as necessary. The nitrogen distribution characteristics were determined using 15N isotope tracing. In addition, the effects of nitrification, denitrification, and microbial composition on soil nitrogen transformation at different depths were studied by microbial functional gene quantification and high-throughput sequencing. The results revealed that in the SWI groups, the total nitrogen leaching loss rate reduced by 0.3-0.8% and the nitrogen use efficiency (NUE) increased by 2.18-4.43% compared with those in the TI groups. After the 15N-labeled nitrogen fertilizer was applied, the main pathways of nitrogen were found to be related to plant absorption and nitrogen residues. Furthermore, paddy soil ammonia-oxidizing archaea were more effective than ammonia-oxidizing bacteria for soil ammonia oxidation by SWI groups. The SWI measures increased the relative abundance of Firmicutes in paddy soil, enhancing the ability of rice to fix nitrogen to produce ammonium nitrogen, thus reducing the dependence of rice on chemical fertilizers. Moreover, SWI enhanced the relative abundance of nirS and nosZ genes within surface soil bacteria, thereby promoting denitrification in the surface soil of paddy fields. SWI also promoted ammonia oxidation and denitrification by increasing the abundance and activity of Proteobacteria, Nitrospirae, and Bacteroidetes. Collectively, SWI effectively reduced the nitrogen leaching loss rate and increase NUE.