Optimizing ultrafast dynamic contrast-enhanced MRI scan duration in the differentiation of benign and malignant breast lesions.

OBJECTIVE: To determine the optimal scan duration for ultrafast DCE-MRI in effectively differentiating benign from malignant breast lesions. METHODS: The study prospectively recruited participants who underwent breast ultrafast DCE-MRI from September 2021 to March 2023. A 30-phase breast ultrafast DCE-MRI on a 3.0-T MRI system was conducted with a 4.5-s temporal resolution. Scan durations ranged from 40.5 s to 135.0 s, during which the analysis is performed at three-phase intervals, forming eight dynamic sets (scan duration [SD]40.5s: 40.5 s, SD54s: 54.0 s, SD67.5s: 67.5 s, SD81s: 81.0 s, SD94.5s: 94.5 s, SD108s: 108.0 s, SD121.5s: 121.5 s, and SD135s: 135.0 s). Two ultrafast DCE-MRI parameters, maximum slope (MS) and initial area under the curve in 60 s (iAUC), were calculated for each dynamic set and compared between benign and malignant lesions. Areas under the receiver operating characteristic curve (AUCs) were used to assess their diagnostic performance. RESULTS: A total of 140 women (mean age, 47 ± 11 years) with 151 lesions were included. MS and iAUC from eight dynamic sets exhibited significant differences between benign and malignant lesions (all p < 0.05), except iAUC at SD40.5s. The AUC of MS (AUC = 0.804) and iAUC (AUC = 0.659) at SD67.5s were significantly higher than their values at SD40.5s (AUC = 0.606 and 0.516; corrected p < 0.05). No significant differences in AUCs for MS and iAUC were observed from SD67.5s to SD135s (all corrected p > 0.05). CONCLUSIONS: Ultrafast DCE-MRI with a 67.5-s scan duration appears optimal for effectively differentiating malignant from benign breast lesions. CRITICAL RELEVANCE STATEMENT: By evaluating scan durations (40.5-135 s) and analyzing two ultrafast DCE-MRI parameters, we found a scan duration of 67.5 s optimal for discriminating between these lesions and offering a balance between acquisition time and diagnostic efficacy. KEY POINTS: Ultrafast DCE-MRI can effectively differentiate malignant from benign breast lesions. A minimum of 67.5-sec ultrafast DCE-MRI scan duration is required to differentiate benign and malignant lesions. Extending the scan duration beyond 67.5 s did not significantly improve diagnostic accuracy.

The Effect of Rhythmic Audio-Visual Stimulation on Inhibitory Control: An ERP Study.

Inhibitory control, as an essential cognitive ability, affects the development of higher cognitive functions. Rhythmic perceptual stimulation has been used to improve cognitive abilities. It is unclear, however, whether it can be used to improve inhibitory control. This study used the Go/NoGo task and the Stroop task to assess various levels of inhibitory control using rhythmic audio-visual stimuli as the stimulus mode. Sixty subjects were randomly divided into three groups to receive 6 Hz, 10 Hz, and white noise stimulation for 30 min. Two tasks were completed by each subject both before and after the stimulus. Before and after the task, closed-eye resting EEG data were collected. The results showed no differences in behavioral and EEG measures of the Go/NoGo task among the three groups. While both 6 Hz and 10 Hz audio-visual stimulation reduced the conflict effect in the Stroop task, only 6 Hz audio-visual stimulation improved the amplitude of the N2 component and decreased the conflict score. Although rhythmic audio-visual stimulation did not enhance response inhibition, it improved conflict inhibition.

Synthesis of ß,ß-Dithioketones by Merging C-C and C-S Bond Cleavage in [1 + 1 + 1 + 1 + 1 + 1] Annulation.

An unconventional [1 + 1 + 1 + 1 + 1 + 1] annulation process was developed for the construction of ß,ß-dithioketones by merging C-C and C-S bond cleavage. In this reaction, rongalite concurrently served as triple C1 units, dual sulfur(II) synthons, and a reductant for the first time. Mechanism investigation indicated that the reaction involved the self-mediated valence state change of rongalite. By performing this step-economical method, the challenging construction of C5-substituted 1,3-dithiane can be achieved under mild and simple conditions.

The role of oxidative stress in intervertebral disc degeneration: Mechanisms and therapeutic implications.

Oxidative stress is one of the main driving mechanisms of intervertebral disc degeneration(IDD). Oxidative stress has been associated with inflammation in the intervertebral disc, cellular senescence, autophagy, and epigenetics of intervertebral disc cells. It and the above pathological mechanisms are closely linked through the common hub reactive oxygen species(ROS), and promote each other in the process of disc degeneration and promote the development of the disease. This reveals the important role of oxidative stress in the process of IDD, and the importance and great potential of IDD therapy targeting oxidative stress. The efficacy of traditional therapy is unstable or cannot be maintained. In recent years, due to the rise of materials science, many bioactive functional materials have been applied in the treatment of IDD, and through the combination with traditional drugs, satisfactory efficacy has been achieved. At present, the research review of antioxidant bioactive materials in the treatment of IDD is not complete. Based on the existing studies, the mechanism of oxidative stress in IDD and the common antioxidant therapy were summarized in this paper, and the strategies based on emerging bioactive materials were reviewed.

Origin and dispersal history of Hepatitis B virus in Eastern Eurasia.

Hepatitis B virus is a globally distributed pathogen and the history of HBV infection in humans predates 10000 years. However, long-term evolutionary history of HBV in Eastern Eurasia remains elusive. We present 34 ancient HBV genomes dating between approximately 5000 to 400 years ago sourced from 17 sites across Eastern Eurasia. Ten sequences have full coverage, and only two sequences have less than 50% coverage. Our results suggest a potential origin of genotypes B and D in Eastern Asia. We observed a higher level of HBV diversity within Eastern Eurasia compared to Western Eurasia between 5000 and 3000 years ago, characterized by the presence of five different genotypes (A, B, C, D, WENBA), underscoring the significance of human migrations and interactions in the spread of HBV. Our results suggest the possibility of a transition from non-recombinant subgenotypes (B1, B5) to recombinant subgenotypes (B2 - B4). This suggests a shift in epidemiological dynamics within Eastern Eurasia over time. Here, our study elucidates the regional origins of prevalent genotypes and shifts in viral subgenotypes over centuries.

Simultaneous Determination of Ibrutinib, Dihydroxydiol Ibrutinib, and Zanubrutinib in Human Plasma by Liquid Chromatography-Mass Spectrometry/Mass Spectrometry.

BACKGROUND: Ibrutinib and zanubrutinib are Bruton tyrosine kinase inhibitors used to treat mantle cell lymphoma, chronic lymphocytic leukemia, and small lymphocytic lymphoma. Dihydroxydiol ibrutinib (DHI) is an active metabolite of the drug. A liquid chromatography-tandem mass spectrometry method was developed to detect ibrutinib, DHI, and zanubrutinib in human plasma. METHODS: The method involved a protein precipitation step, followed by chromatographic separation using a gradient of 10 mM ammonium acetate (containing 0.1% formic acid)-acetonitrile. Ibrutinib-d5 was used as an internal standard. Analytes were separated within 6.5 minutes. The optimized multiple reaction monitoring transitions of m/z 441.1 → 304.2, 475.2 → 304.2, 472.2 → 455.2, and 446.2 → 309.2 were selected to inspect ibrutinib, DHI, zanubrutinib, and the internal standards in positive ion mode. RESULTS: The validated curve ranges included 0.200-800, 0.500-500, and 1.00-1000 ng/mL for ibrutinib, DHI, and zanubrutinib, respectively. The precisions of the lower limit of quantification of samples were below 15.5%, the precisions of the other level samples were below 11.4%, and the accuracies were between -8.6% and 8.4%. The matrix effect and extraction recovery of all compounds ranged between 97.6%-109.0% and 93.9%-105.2%, respectively. The selectivity, accuracy, precision, matrix effect, and extraction recovery results were acceptable according to international method validation guidelines. CONCLUSIONS: A simple and rapid method was developed and validated in this study. This method was used to analyze plasma concentrations of ibrutinib and zanubrutinib in patients with mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, or diffuse large B-cell lymphoma. The selected patients were aged between 44 and 74 years.

Transcriptome Expression Profiling Reveals the Molecular Response to Salt Stress in Gossypium anomalum Seedlings.

Some wild cotton species are remarkably tolerant to salt stress, and hence represent valuable resources for improving salt tolerance of the domesticated allotetraploid species Gossypium hirsutum L. Here, we first detected salt-induced stress changes in physiological and biochemical indexes of G. anomalum, a wild African diploid cotton species. Under 350 mmol/L NaCl treatment, the photosynthetic parameters declined significantly, whereas hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents increased. Catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) activity and proline (PRO) content also significantly increased, reaching peak values at different stages of salt stress. We used RNA-Seq to characterize 15,476 differentially expressed genes in G. anomalum roots after 6, 12, 24, 72, and 144 h of salt stress. Gene Ontology enrichment analysis revealed these genes to be related to sequence-specific DNA and iron ion binding and oxidoreductase, peroxidase, antioxidant, and transferase activity; meanwhile, the top enriched pathways from the Kyoto Encyclopedia of Genes and Genomes database were plant hormone signal transduction, phenylpropanoid biosynthesis, fatty acid degradation, carotenoid biosynthesis, zeatin biosynthesis, starch and sucrose metabolism, and MAPK signaling. A total of 1231 transcription factors were found to be expressed in response to salt stress, representing ERF, MYB, WRKY, NAC, C2H2, bZIP, and HD-ZIP families. Nine candidate genes were validated by quantitative real-time PCR and their expression patterns were found to be consistent with the RNA-Seq data. These data promise to significantly advance our understanding of the molecular response to salt stress in Gossypium spp., with potential value for breeding applications.

Hydrogeochemical and isotopic evidences of the underlying produced water intrusion into shallow groundwater in an oil production area, Northwest China.

The extensive use of fossil fuels (e.g., oil) poses a hidden danger to groundwater quality. However, inorganic pollution has received limited attention compared to organic pollution. In this study, the potential contaminant sources to shallow groundwater were investigated using hydrochemical (e.g., major and trace elements) and isotopic (δ2H and δ18O) methods at an oil field, northwest China, with emphasis on the identification of produced water (PW; oil production-related water) intrusion. The results showed that the groundwater samples can be chemically and isotopically classified into two groups: Group A (severely polluted) and B (slightly or non- polluted). The hydrochemical characteristics of Group A were similar to that of PW, with a comparable Na+/Cl- ratio and elevated levels of Na+, Ca2+, Cl-, Br-, Sr, Ba, Li, B and total volatile organic compounds (TVOCs; volatile and semi-volatile) concentration, but lower HCO3- and SO42- contents, and depleted δ2H and δ18O, which was not suitable for drinking. Groundwater salinity sources involve mineral dissolution (silicate, carbonate and evaporite), cation exchange and anaerobic microbial degradation, as well as deep PW intrusion (especially in Group A). The Cl mixing model showed that PW contributed 13.63-27.78 % to Group A, supported by the results of the isotope mixing model based on δ2H and δ18O (24.43-33.29 %). An overall pollution conceptual model involves three modes: fracturing, surface infiltration, and groundwater lateral runoff. This study validates the effectiveness of Na, Cl, Br, Sr, Ba, Li and B as favorable tracers for monitoring PW intrusion.

Spatiotemporal successions of N, S, C, Fe, and As cycling genes in groundwater of a wetland ecosystem: Enhanced heterogeneity in wet season.

Microorganisms in wetland groundwater play an essential role in driving global biogeochemical cycles. However, largely due to the dynamics of spatiotemporal surface water-groundwater interaction, the spatiotemporal successions of biogeochemical cycling in wetland groundwater remain poorly delineated. Herein, we investigated the seasonal coevolution of hydrogeochemical variables and microbial functional genes involved in nitrogen, carbon, sulfur, iron, and arsenic cycling in groundwater within a typical wetland, located in Poyang Lake Plain, China. During the dry season, the microbial potentials for dissimilatory nitrate reduction to ammonium and ammonification were dominant, whereas the higher potentials for nitrogen fixation, denitrification, methane metabolism, and carbon fixation were identified in the wet season. A likely biogeochemical hotspot was identified in the area located in the low permeable aquifer near the lake, characterized by reducing conditions and elevated levels of Fe2+ (6.65-17.1 mg/L), NH4+ (0.57-3.98 mg/L), total organic carbon (1.02-1.99 mg/L), and functional genes. In contrast to dry season, higher dissimilarities of functional gene distribution were observed in the wet season. Multivariable statistics further indicated that the connection between the functional gene compositions and hydrogeochemical variables becomes less pronounced as the seasons transition from dry to wet. Despite this transition, Fe2+ remained the dominant driving force on gene distribution during both seasons. Gene-based co-occurrence network displayed reduced interconnectivity among coupled C-N-Fe-S cycles from the dry to the wet season, underpinning a less complex and more destabilizing occurrence pattern. The rising groundwater level may have contributed to a reduction in the stability of functional microbial communities, consequently impacting ecological functions. Our findings shed light on microbial-driven seasonal biogeochemical cycling in wetland groundwater.

Discovery of novel Akt1 inhibitors by an ensemble-based virtual screening method, molecular dynamics simulation, and in vitro biological activity testing.

Akt1, as an important member of the Akt family, plays a controlled role in cancer cell growth and survival. Inhibition of Akt1 activity can promote cancer cell apoptosis and inhibit tumor growth. Therefore, in this investigation, a multilayer virtual screening approach, including receptor-ligand interaction-based pharmacophore, 3D-QSAR, molecular docking, and deep learning methods, was utilized to construct a virtual screening platform for Akt1 inhibitors. 17 representative compounds with different scaffolds were identified as potential Akt1 inhibitors from three databases. Among these 17 compounds, the Hit9 exhibited the best inhibitory activity against Akt1 with inhibition rate of 33.08% at concentration of 1 µM. The molecular dynamics simulations revealed that Hit9 and Akt1 could form a compact and stable complex. Moreover, Hit9 interacted with some key residues by hydrophobic, electrostatic, and hydrogen bonding interactions and induced substantial conformation changes in the hinge region of the Akt1 active site. The average binding free energies for the Akt1-CQU, Akt1-Ipatasertib, and Akt1-Hit9 systems were - 34.44, - 63.37, and - 39.14 kJ mol-1, respectively. In summary, the results obtained in this investigation suggested that Hit9 with novel scaffold may be a promising lead compound for developing new Akt1 inhibitor for treatment of various cancers with Akt1 overexpressed.

Finite element analysis of the use of two new types of internal fixation for acetabular fractures.

BACKGROUND: Both-column fracture is a common type of acetabular fracture and is sometimes accompanied by a comminuted fracture of the quadrilateral area. Such fractures are difficult to anatomically reduce and securely fix. In this study, the authors compared the application value and mechanical properties of the Bespoke 3D-printed titanium alloy plates and Union Plate in acetabular both-column fractures. METHODS: A both-column fracture model of the acetabulum was established, and the Bespoke 3D-printed titanium alloy plates, Union Plate and a common reconstruction plate were used for fixation. External loads were applied to the model at different angles, and the effects on the plates and the stress and displacement of the screws were determined. RESULTS: Under different states of hip joint activity, the maximum stress experienced by the Bespoke 3D-printed titanium alloy plates and Union Plate was significantly smaller than the maximum stress experienced by the common reconstruction plate. The Bespoke 3D-printed titanium alloy plates experienced the lowest maximum stress under different hip joint motions. There was no statistically significant difference between the maximum displacement of the Bespoke 3D-printed titanium alloy plates and Union Plate and that of the common reconstructed plate. CONCLUSIONS: The design of the Bespoke 3D-printed titanium alloy plates imparts a smaller maximum stress and better mechanical properties when repairing acetabular both-column fractures.

Deterministic factors modulating assembly of groundwater microbial community in a nitrogen-contaminated and hydraulically-connected river-lake-floodplain ecosystem.

The river-lake-floodplain system (RLFS) undergoes intensive surface-groundwater mass and energy exchanges. Some freshwater lakes are groundwater flow-through systems, serving as sinks for nitrogen (N) entering the lake. Despite the threat of cross-nitrogen contamination, the assembly of the microbial communities in the RLFS was poorly understood. Herein, the distribution, co-occurrence, and assembly pattern of microbial community were investigated in a nitrogen-contaminated and hydraulically-connected RLFS. The results showed that nitrate was widely distributed with greater accumulation on the south than on the north side, and ammonia was accumulated in the groundwater discharge area (estuary and lakeshore). The heterotrophic nitrifying bacteria and aerobic denitrifying bacteria were distributed across the entire area. In estuary and lakeshore with low levels of oxidation-reduction potential (ORP) and high levels of total organic carbon (TOC) and ammonia, dissimilatory nitrate reduction to ammonium (DNRA) bacteria were enriched. The bacterial community had close cooperative relationships, and keystone taxa harbored nitrate reduction potentials. Combined with multivariable statistics and self-organizing map (SOM) results, ammonia, TOC, and ORP acted as drivers in the spatial evolution of the bacterial community, coincidence with the predominant deterministic processes and unique niche breadth for microbial assembly. This study provides novel insight into the traits and assembly of bacterial communities and potential nitrogen cycling capacities in RLFS groundwater.

LC-MS/MS methods for determination of venetoclax in human plasma and cerebrospinal fluid.

We developed and validated sensitive MS/MS methods for the determination of venetoclax, an oral selective B-cell lymphoma-2 inhibitor, in human plasma and cerebrospinal fluid (CSF). Acetonitrile was used as protein precipitant. The mobile phase was 10 mM ammonium formate consisting of 0.1% formic acid and acetonitrile (40:60, v/v). The analytes were separated on an ACQUITY UPLC HSS T3 column (2.1 × 50 mm, 1.8 µm) in 5 min. An API 4000 mass spectrometer was selected to quantify venetoclax and internal standard using m/z 868.3 → 636.3 and 876.3 → 644.3 under multiple response monitoring mode. In plasma, the calibration curve exhibited good linearity ranging from 20.0 to 5000 ng/mL, whereas in the CSF, the linear range was 0.500-100 ng/mL. The matrix effect of venetoclax and internal standard (venetoclax-d8) was not obvious in both plasma and CSF. The inter- and intra-run accuracy was within ±11.9%, and the inter- and intra-run precision was below 13.6%. Both methods had no carryover, and the recovery was close to 100%. The validated methods were employed to quantify the concentrations of venetoclax in the plasma and CSF of patients diagnosed with chronic lymphocytic leukemia or acute myelogenous leukemia.

Reductive N-Formylation of Nitroarenes Mediated by Rongalite.

Herein, we disclose a straightforward approach to access transition-metal-free reductive N-formylation of nitroarenes. This reaction integrates the dual role of rongalite, which acts as a reductant and a C1 building block concurrently. This provides an alternative method for the synthesis of N-aryl formamides from nitroarenes, including the construction of a C-N bond. The utility of this protocol was demonstrated by scale-up synthesis and late-stage functionalizations of complex molecules.

A recessive LRR-RLK gene causes hybrid breakdown in cotton.

KEY MESSAGE: An LRR-RLK gene causing interspecific hybrid breakdown between Gossypium. anomalum and G. hirsutum was identified by deploying a map-based cloning strategy. The self-destructing symptoms of hybrid incompatibility in most cases are attributed to autoimmunity. The cloning of genes responsible for hybrid incompatibility in cotton is helpful to clarify the mechanisms underlying hybrid incompatibility and can break the barriers in distant hybridization. In this study, a temperature-dependent lethality was identified in CSSL11-9 (chromosome segment substitution line) with Gossypium anomalum chromosome segment on chromosome A11. Transcriptome analysis showed the differentially expressed genes related to autoimmune responses were highly enriched, suggesting that expression of CSSL11-9 plant lethal gene activated autoimmunity in the absence of any pathogen or external stimulus, inducing programmed cell death (PCD) and causing a lethal phenotype. The lethal phenotype was controlled by a pair of recessive genes and then fine mapped between JAAS3191-JAAS3050 interval, which covered 63.87 kb in G. hirsutum genome and 98.66 kb in G. anomalum. We demonstrated that an LRR-RLK gene designated as hybrid breakdown 1 (GoanoHBD1) was the causal gene underlying this locus for interspecific hybrid incompatibility between G. anomalum and G. hirsutum. Silencing this LRR-RLK gene could restore CSSL11-9 plants from a lethal to a normal phenotype. Our findings provide new insights into reproductive isolation and may benefit cotton breeding.

I2-DMSO-Mediated Transannulation of Benzo[d]isoxazol-3-amine: Direct Access to 2,4,5-Substituted Pyrimidine Derivatives.

An I2-DMSO-mediated multicomponent [3+1+2] cascade annulation reaction using aryl methyl ketones, enaminones, and benzo[d]isoxazol-3-amine as substrates has been developed. This metal-free reaction involved the transannulation of benzo[d]isoxazol-3-amines with the formation of two C-N bonds and a C-C bond in one pot. Notably, a pyrimidine ring with a 1,4-dicarbonyl scaffold could efficiently transform into a pyrimido[4,5-d]pyridazine skeleton. The phenolic hydroxyl group of the target product could undergo further modification with pharmaceuticals, demonstrating the utility of this method.

Alpha and Theta Oscillations Are Causally Linked to Interference Inhibition: Evidence from High-Definition Transcranial Alternating Current Stimulation.

(1) Background: The Go/NoGo task and color-word Stroop task were used to investigate the effect of applying different frequency bands of neural oscillations to the lDLPFC on inhibitory control modulation. (2) Methods: Participants were randomly categorized into four groups and received HD-tACS at 6, 10, and 20 Hz or sham stimulation at 1.5 mA for 20 min. All participants performed a color-word Stroop task and Go/NoGo task before and immediately after the stimulation; closed-eye resting-state EEG signals were acquired for 3 min before and after the tasks. (3) Results: There were no significant differences in the Go/NoGo behavioral indices task across the four groups. In the color-word Stroop task, the Stroop effect of response time was significantly reduced by 6 and 10 Hz stimulations compared to sham stimulation, and the Stroop effect of accuracy was significantly reduced by 10 Hz stimulation. There were no significant differences in the frequency range-specific (delta, theta, alpha, beta, or gamma) resting EEG power before and after stimulation. (4) Conclusions: HD-tACS at 6 and 10 Hz effectively improved participants' performance on the color-word Stroop task, demonstrating the importance of the lDLPFC in interference inhibition and supporting a causal relationship between theta and alpha oscillations in interference inhibition.

Successive Promotion of Formal [3+2] Cycloaddition of Aryl Methyl Ketones by I2 and Zn: Access to 2-Hydroxy-4-morpholin-2,5-diarylfuran-3(2H)-ones with a Quaternary Carbon Center.

2-Hydroxy-4-morpholin-2,5-diarylfuran-3(2H)-one derivatives were constructed sequentially using iodine and zinc dust from simple and readily available methyl ketone and morpholine as the starting materials. Under mild conditions, C-C, C-N, and C-O bonds formed in a one-pot synthesis. A quaternary carbon center was successfully constructed, and the active drug fragment morpholine was introduced into the molecule.

Determination of Orelabrutinib in Human Plasma Using LC-MS/MS.

BACKGROUND: Orelabrutinib is a second-generation Bruton tyrosine kinase inhibitor that improves the management of B-cell malignancies. The objective of this study was to develop and validate an LC-MS/MS method for quantifying orelabrutinib in human plasma. METHODS: Plasma samples were processed using acetonitrile to precipitate proteins. Ibrutinib-d5 was used as the internal standard. The mobile phase comprised 10 mM ammonium formate containing 0.1% formic acid and acetonitrile (62:38, vol/vol). The multiple reaction monitoring transitions at m / z = 428.1 → 411.2 and 446.2 → 309.2 were selected for orelabrutinib and ibrutinib-d5, respectively, after ionization in the positive mode. RESULTS: Total runtime was 4.5 minutes. The validated curve ranges were 1.00-500 ng/mL. This method exhibited acceptable selectivity, dilution integrity, matrix effects, and recovery. Interrun and intrarun accuracy ranged from -3.4% to 6.5%, and interrun and intrarun precision was between 2.8% and 12.8%. Stability was studied under different conditions. The incurred sample reanalysis demonstrated good reproducibility. CONCLUSIONS: The LC-MS/MS method provided a simple, specific, and rapid quantification of orelabrutinib in the plasma of patients with mantle cell lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma. The results indicated that orelabrutinib exhibits large variability between individuals and should be prudently used in combination with CYP3A4 inhibitors.

Nitrogen species and microbial community coevolution along groundwater flowpath in the southwest of Poyang Lake area, China.

Nitrate and ammonia overload in groundwater can lead to eutrophication of surface water in areas where surface water is recharged by groundwater. However, this process remained elusive due to the complicated groundwater N cycling, which is governed by the co-evolution of hydrogeochemical conditions and N-cycling microbial communities. Herein, this process was studied along a generalized groundwater flowpath in Ganjing Delta, Poyang Lake area, China. From groundwater recharge to the discharge area near the lake, oxidation-reduction potential (ORP), NO3-N, and NO2-N decreased progressively, while NH3-N, total organic carbon (TOC), Fe2+, sulfide, and TOC/NO3- ratio accumulated in the lakeside samples. The anthropogenic influences such as sewage and agricultural activities drove the nitrate distribution, as observed by Cl- vs. NO3-/Cl- ratio and isotopic composition of nitrate. The hydrogeochemical evolution was intimately coupled with the changes in microbial communities. Variations in microbial community structures was significantly explained by Fe2+, NH3-N, and sulfide, while TOC/NO3- controlled the distribution of predicted N cycling gene. The absence of NH3-N in groundwater upstream was accompanied by the enrichment in Acinetobacter capable of nitrification and aerobic denitrification. These two processes were also supported by Ca2+ + Mg2+ vs. HCO3- ratio and isotopic composition of NO3-. The DNRA process downstream was revealed by both the presence of DNRA-capable microbes such as Arthrobacter and the isotopic composition of NH4+ in environments with high concentrations of NH3-N, TOC/NO3-, Fe2+, and sulfide. This coupled evolution of N cycling and microbial community sheds new light on the N biogeochemical cycle in areas where surface water is recharged by groundwater.