Low- and moderate-intensity aerobic exercise improves the physiological acclimatization of lowlanders on the Tibetan plateau.

This study investigates whether exercise as a strategy for improving physical fitness at sea level also offers comparable benefits in the unique context of high altitudes (HA), considering the physiological challenges of hypoxic conditions. Overall, 121 lowlanders who had lived on the Tibetan Plateau for >2 years and were still living at HA during the measurements were randomly classified into four groups. Each individual of the low-intensity (LI), moderate-intensity (MI), and high-intensity (HI) groups performed 20 sessions of aerobic exercise at HA (3680 m) over 4 weeks, while the control group (CG) did not undergo any intervention. Physiological responses before and after the intervention were observed. The LI and MI groups experienced significant improvement in cardiopulmonary fitness (0.27 and 0.35 L/min increases in peak oxygen uptake [ V ˙ $\dot{\mathrm{V}}$ O2peak], both p < 0.05) after exercise intervention, while the hematocrit (HCT) remained unchanged (p > 0.05). However, HI exercise was less efficient for cardiopulmonary fitness of lowlanders (0.02 L/min decrease in V ˙ $\dot{\mathrm{V}}$ O2peak, p > 0.05), whereas both the HCT (1.74 %, p < 0.001) and glomerular filtration rate (18.41 mL/min, p < 0.001) increased with HI intervention. Therefore, LI and MI aerobic exercise, rather than HI, can help lowlanders in Tibet become more acclimated to the HA by increasing cardiopulmonary function and counteracting erythrocytosis.

Neurological involvement in hematopoietic stem cell transplantation-associated thrombotic microangiopathy.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a well-recognized serious complication of hematopoietic stem cell transplantation (HSCT). The understanding of TA-TMA pathophysiology has expanded in recent years. Dysregulation of the complement system is thought to cause endothelial injury and, consequently, microvascular thrombosis and tissue damage. TA-TMA can affect multiple organs, and each organ exhibits specific features of injury. Central nervous system (CNS) manifestations of TA-TMA include posterior reversible encephalopathy syndrome, seizures, and encephalopathy. The development of neurological dysfunction is associated with a significantly lower overall survival in patients with TA-TMA. However, there are currently no established histopathological or radiological criteria for the diagnosis of CNS TMA. Patients who receive total body irradiation (TBI), calcineurin inhibitors (CNI), and severe acute and chronic graft-versus-host disease (GVHD) are at a high risk of experiencing neurological complications related to TA-TMA and should be considered for directed TA-TMA therapy. However, the incidence and clinical manifestations of TA-TMA neurotoxicity remain unclear. Studies specifically examining the involvement of CNS in TMA syndromes are limited. In this review, we discuss clinical manifestations and imaging abnormalities in patients with nervous system involvement in TA-TMA. We summarize the mechanisms underlying TA-TMA and its neurological complications, including endothelial injury, evidence of complement activation, and treatment options for TA-TMA.

Insight into N2O emission and denitrifier communities under different aeration intensities in composting of cattle manure from perspective of multi-factor interaction analysis.

Nitrous oxide (N2O) emission from composting is a significant contributor to greenhouse effect and ozone depletion, which poses a threat to environment. To address the challenge of mitigating N2O emission during composting, this study investigated the response of N2O emission and denitrifier communities (detected by metagenome sequencing) to aeration intensities of 6 L/min (C6), 12 L/min (C12), and 18 L/min (C18) in cattle manure composting using multi-factor interaction analysis. Results showed that N2O emission occurred mainly at mesophilic phase. Cumulative N2O emission (QN2O, 9.79 mg·kg-1 DW) and total nitrogen loss (TN loss, 16.40 %) in C12 composting treatment were significantly lower than those in the other two treatments. The lower activity of denitrifying enzymes and the more complex and balanced network of denitrifiers and environmental factors might be responsible for the lower N2O emission. Denitrification was confirmed to be the major pathway for N2O production. Moisture content (MC) and Luteimonas were the key factors affecting N2O emission, and nosZ-carrying denitrifier played a significant role in reducing N2O emission. Although relative abundance of nirS was lower than that of nirK significantly (P < 0.05), nirS was the key gene influencing N2O emission. Community composition of denitrifier varied significantly with different aeration treatments (R2 = 0.931, P = 0.001), and Achromobacter was unique to C12 at mesophilic phase. Physicochemical factors had higher effect on QN2O, whereas denitrifying genes, enzymes and NOX- had lower effect on QN2O in C12. The complex relationship between N2O emission and the related factors could be explained by multi-factor interaction analysis more comprehensively. This study provided a novel understanding of mechanism of N2O emission regulated by aeration intensity in composting.

Menthol-Modified Quercetin Liposomes with Brain-Targeting Function for the Treatment of Senescent Alzheimer's Disease.

Oxidative stress and neuroinflammation in the aging brain are correlated with the development of neurodegenerative diseases, such as Alzheimer's disease (AD). The blood-brain barrier (BBB) poses a significant challenge to the effective delivery of therapeutics for AD. Prior research has demonstrated that menthol (Men) can augment the permeability of the BBB. Consequently, in the current study, we modified Men on the surface of liposomes to construct menthol-modified quercetin liposomes (Men-Qu-Lips), designed to cross the BBB and enhance quercetin (Qu) concentration in the brain for improved therapeutic efficacy. The experimental findings indicate that Men-Qu-Lips exhibited good encapsulation efficiency and stability, successfully crossed the BBB, improved oxidative stress and neuroinflammation in the brains of aged mice, protected neurons, and enhanced their learning and memory abilities.

Genetic prediction of causal association between serum bilirubin and hematologic malignancies: a two-sample Mendelian randomized and bioinformatics study.

Introduction: An increasing number of cohort studies have shown a correlation between serum bilirubin and tumors, but no definitive causal relationship has been established between serum bilirubin and hematological malignancies.Therefore, the aim of the present study was to assess the causal relationship of serum bilirubin, including total bilirubin (TBIL) and direct bilirubin (DBIL), with hematological malignancies, including leukemia, lymphoma, and myeloma. Methods: We used a genome-wide association study (GWAS) collection of TBIL, DBIL, and hematological malignancies data. Using two-sample Mendelian randomization(MR), we assessed the impact of TBIL and DBIL on hematological malignancies. For this study, the inverse variance weighting method (IVW) was the primary method of MR analysis. In the sensitivity analysis, the weighted median method, MR Egger regression, and MR-PRESSO test were used. To understand the mechanisms behind TBIL and DBIL, we used three different approaches based on screening single nucleotide polymorphisms (SNPs) and their associated genes, followed by bioinformatics analysis. Results: The IVW test results showed evidence of effects of TBIL (odds ratio [OR]: 4.47, 95% confidence interval [CI]: 1.58-12.62) and DBIL (OR: 3.31, 95% CI: 1.08-10.18) on the risk of acute myeloid leukemia (AML).The findings from bioinformatics indicated that TBIL could potentially undergo xenobiotic metabolism through cytochrome P450 and contribute to chemical carcinogenesis. Discussion: In this study, two-sample MR analysis revealed a causal relationship between TBIL, DBIL, and AML.

Elucidating immune cell dynamics in chronic lung allograft dysfunction: A comprehensive single-cell transcriptomic study.

Chronic Lung Allograft Dysfunction (CLAD) is a critical post-transplant complication that predominantly determines the long-term survival rates and quality of life of patients undergoing lung transplantation. The limited efficacy of current immunosuppressive strategies underscores our incomplete understanding of the immunological aspects of CLAD. Hence, there is an urgent need for more comprehensive and targeted research to unravel the complex interplay of immune cells in the development and progression of CLAD. This study conducts an in-depth analysis of the immune environment in CLAD. By examining the gene expression profiles of T cells, natural killer cells, B cells, macrophages, and monocytes, we have elucidated a unique immunological landscape in CLAD compared to healthy controls. We highlight the heterogeneity within the immune populations and provide a comprehensive understanding of the immune mechanisms driving CLAD. Enrichment analysis identified specific pathways that are either overactive or suppressed in CLAD, revealing potential molecular targets for therapeutic intervention. Our findings emphasize the crucial role of T cells in the pathophysiology of CLAD, coordinating the immune response and revealing an amplified immune cell network, potentially leading to maladaptive tissue responses. By integrating a comprehensive cellular and molecular portrait of the immune environment, our research not only deepens our understanding of the pathogenesis of CLAD but also lays a foundational approach for the development of targeted therapies.

High-multiplex single-cell imaging analysis reveals tumor immune contexture associated with clinical outcomes after CAR T cell therapy.

Chimeric antigen receptor (CAR) T cell therapy has made great progress in treating lymphoma, yet patient outcomes still vary greatly. The lymphoma microenvironment may be an important factor in the efficacy of CAR T therapy. In this study, we designed a highly multiplexed imaging mass cytometry (IMC) panel to simultaneously quantify 31 biomarkers from 13 patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) who received CAR19/22 T cell therapy. A total of 20 sections were sampled before CAR T cell infusion or after infusion when relapse occurred. A total of 35 cell clusters were identified, annotated, and subsequently redefined into 10 metaclusters. The CD4+ T cell fraction was positively associated with remission duration. Significantly higher Ki67, CD57, and TIM3 levels and lower CD69 levels in T cells, especially the CD8+/CD4+ Tem and Te cell subsets, were seen in patients with poor outcomes. Cellular neighborhood containing more immune cells was associated with longer remission. Fibroblasts and vascular endothelial cells resided much closer to tumor cells in patients with poor response and short remission after CAR T therapy. Our work comprehensively and systematically dissects the relationship between cell composition, state, and spatial arrangement in the DLBCL microenvironment and the outcomes of CAR T cell therapy, which is beneficial to predict CAR T therapy efficacy.

Improving prediction of N2O emissions during composting using model-agnostic meta-learning.

Nitrous oxide (N2O) represents a significant environmental challenge as a harmful, long-lived greenhouse gas that contributes to the depletion of stratospheric ozone and exacerbates global anthropogenic greenhouse warming. Composting is considered a promising and economically feasible strategy for the treatment of organic waste. However, recent research indicates that composting is a source of N2O, contributing to atmospheric pollution and greenhouse effect. Consequently, there is a need for the development of effective, cost-efficient methodologies to quantify N2O emissions accurately. In this study, we employed the model-agnostic meta-learning (MAML) method to improve the performance of N2O emissions prediction during manure composting. The highest R2 and lowest root mean squared error (RMSE) values achieved were 0.939 and 18.42 mg d-1, respectively. Five machine learning methods including the backpropagation neural network, extreme learning machine, integrated machine learning method based on ELM and random forest, gradient boosting decision tree, and extreme gradient boosting were adopted for comparison to further demonstrate the effectiveness of the MAML prediction model. Feature analysis showed that moisture content of structure material and ammonium concentration during composting process were the two most significant features affecting N2O emissions. This study serves as proof of the application of MAML during N2O emissions prediction, further giving new insights into the effects of manure material properties and composting process data on N2O emissions. This approach helps determining the strategies for mitigating N2O emissions.

Case report: The utilization of crizotinib and brentuximab vedotin as a bridge to autologous stem cell transplantation and followed by CD30-directed CAR-T cell therapy in relapsed/refractory ALK+ ALCL.

Background: Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL) is a rare, mature T-cell non-Hodgkin lymphoma. The prognosis of patients with relapsed or refractory ALCL following first-line chemotherapy is extremely poor. NCCN guidelines recommend intensified chemotherapy with or without ASCT consolidation for r/r ALCL, however, this is not an effective treatment for all ALK+ALCL. Case report: Herein, we report a patient with relapsed/refractory ALK+ ALCL who received crizotinib and brentuximab vedotin as bridging therapy, followed by autologous stem cell transplantation and sequential anti-CD30 CAR T cell therapy. Conclusion: The patient achieved complete remission and long-term disease-free survival of months and continues to be followed up. The combination therapy model in this case may provide guidance for the management of relapsed/refractory ALK+ ALCL, and further prospective trials are needed to confirm its effectiveness.

Bacteriophage therapy for drug-resistant Staphylococcus aureus infections.

Drug-resistant Staphylococcus aureus stands as a prominent pathogen in nosocomial and community-acquired infections, capable of inciting various infections at different sites in patients. This includes Staphylococcus aureus bacteremia (SaB), which exhibits a severe infection frequently associated with significant mortality rate of approximately 25%. In the absence of better alternative therapies, antibiotics is still the main approach for treating infections. However, excessive use of antibiotics has, in turn, led to an increase in antimicrobial resistance. Hence, it is imperative that new strategies are developed to control drug-resistant S. aureus infections. Bacteriophages are viruses with the ability to infect bacteria. Bacteriophages, were used to treat bacterial infections before the advent of antibiotics, but were subsequently replaced by antibiotics due to limited theoretical understanding and inefficient preparation processes at the time. Recently, phages have attracted the attention of many researchers again because of the serious problem of antibiotic resistance. This article provides a comprehensive overview of phage biology, animal models, diverse clinical case treatments, and clinical trials in the context of drug-resistant S. aureus phage therapy. It also assesses the strengths and limitations of phage therapy and outlines the future prospects and research directions. This review is expected to offer valuable insights for researchers engaged in phage-based treatments for drug-resistant S. aureus infections.

Bioequivalence of Blonanserin Tablets Under Fasting and Fed Conditions in Healthy Chinese Subjects.

Blonanserin is a novel oral antischizophrenic drug. Under fasting (n = 50) and fed (n = 60) conditions, this study compared the bioequivalence of the generic blonanserin tablet with the reference blonanserin tablet. In this single-center, randomized, open-label, 2-period, 2-sequence, crossover study, 110 patients were randomly given a 4-mg dose of either the test or reference blonanserin tablet with a 14-day washout period. Blood samples were taken before performing and up to 72 hours following. A validated high-performance liquid chromatography-tandem mass spectrometry technique was used to measure the levels of blonanserin in plasma. Safety was evaluated throughout the study. The study found no significant differences in the maximum observed drug concentration in the plasma (Cmax ), the area under the plasma concentration-time curve from time 0 to the last sampling time (AUC0-t ), and the area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞ ) between the 2 blonanserin formulations. The 90% confidence intervals of the geometric mean ratio of the test/reference formulations for Cmax , AUC0-t , and AUC0-∞ were within the 80%-125% limit. Food dramatically raised blonanserin exposure, and also significantly prolonged the lag time of absorption. No serious adverse events occurred. These results indicate that the 2 blonanserin formulations were bioequivalent and well tolerated in healthy Chinese subjects. In clinical treatment, it is necessary to consider the food effect of blonanserin.

Assessment and predictive ability of the absolute neutrophil count in peripheral blood for in vivo CAR T cells expansion and CRS.

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy is an advanced and effective immunotherapy for relapsed or refractory B-cell malignancies. High expansion of CAR T cells in vivo and durable antitumor activity indicate a persistent therapeutic response. However, this treatment is linked to a high frequency of adverse events, such as cytokine release syndrome (CRS), which affects its efficacy and can even be life-threatening. At present, a variety of markers associated with clinical response and treatment toxicity after CAR T cells infusion have been reported. Although these biomarkers can act as effective indicators reflecting CAR T cells expansion as well as CRS, they fail to predict the expansion rate of CAR T cells. Hence, further investigation is urgent to find a new biomarker to fill this void. METHODS: We analyzed the association between the absolute neutrophil count (ANC) and CAR expansion and CRS in 45 patients with B-cell malignancies from two clinical trials. We proposed that ANC could be a practical biomarker for CAR T cells expansion and CRS, and conducted a feasibility analysis on its predictive ability. RESULTS: In this study, 17 B-cell hematological malignancy patients with anti-B-cell maturation antigen CAR-treated and 28 with CAR19/22 T-cell-treated were enrolled and divided into an ANC-absence group and an ANC-presence group. The results showed that ANC absence correlated positively with CAR expansion and the expansion rate. The ANC can be used as a predictive marker for CAR T cells expansion. Moreover, the patients with ANC absence experienced a more severe CRS, and ANC performed a predictive ability for CRS. In addition, the peak serum concentration of several cytokines involved in CRS was higher in patients with ANC absence. CONCLUSION: Thus, we suggest ANC as an evaluative and predictive biomarker for CAR expansion and CRS during CAR T cell therapy, which can help to maximize clinical efficacy, reduce treatment-related toxicity and prolong survival.

Multiplexed on-site sample-in-result-out test through microfluidic real-time PCR (MONITOR) for the detection of multiple pathogens causing influenza-like illness.

IMPORTANCE: This study combines quantitative polymerase chain reaction (qPCR) and microfluidics to introduce MONITOR, a portable field detection system for multiple pathogens causing influenza-like illness. MONITOR can be rapidly deployed to enable simultaneous sample-in-result-out detection of eight common influenza-like illness (ILI) pathogens with heightened sensitivity and specificity. It is particularly well suited for communities and regions without centralized laboratories, offering robust technical support for the prompt and accurate monitoring and detection of ILI. It holds the potential to be a potent tool in the early detection and prevention of infectious diseases.

An instant inertia estimated and operation burden considered frequency regulation method for low inertia power systems.

The application of virtual inertia (VI) has become a novel solution and new orientation for the frequency regulation of the high variable renewable energy (VRE) penetrated low inertia systems. How to provide a frequency regulation strategy for the system with VI is a key problem. Firstly, the power system is a multi inputs multi outputs (MIMO) system, in which the coupling characteristics of VI control and the primary and secondary frequency controls can't be ignored. Secondly, the system inertia constant is time-varying and the estimation of it is crucial for gaining a satisfying regulation performance. This paper intends to provide a frequency regulation strategy for this problem. In this work, an Elman neural network (ENN) based inertia estimation with a deadband method is proposed for the identification of the system's instant inertia. And the Laguerre function-based rate of change of frequency (ROCOF) constrained MIMO-MPC is constructed to provide the collaboration strategy. Then, the control parameters are tuned by the gravitational search algorithm (GSA) considering both the system performance indexes and the operation burden indexes. The proposed strategy is testified based on a three-area power system. The results prove not only the robustness of the controller but also the effectiveness of the ROCOF constraint, the operation burden index, and the instant inertia estimation method.

Case Report: A recurrent case of ALK-ALCL after autologous transplantation was successfully treated with BV + a modified CHEP chemotherapy containing mitoxantrone hydrochloride liposome with the addition of chidamide maintenance therapy.

Background: ALK-negative anaplastic large cell lymphoma (ALK-ALCL) is a rare heterogeneous malignancy of T-cell origin.ALK- ALCL has a poor prognosis, with more patients experiencing relapses and refractory to treatment, and its treatment remains challenging. We report a case with bone involvement as the main clinical manifestation of recurrent, and the patient achieved significant partial remission after brentuximab vedotin(BV) combined with a modified CHEP chemotherapy containing mitoxantrone hydrochloride liposome (PLM60) with the addition of chidamide maintenance therapy and received regular follow-up, with a disease-free survival of 16 months to date. A literature review of the clinical presentation and treatment of ALCL was also conducted to identify strategies for its diagnosis and management. Conclusions: ALK-ALCL with bone involvement as the main manifestation of recurrent is relatively rare. Here, BV combined a modified CHEP chemotherapy containing mitoxantrone hydrochloride liposome was applied for the first time in a patient with relapsed ALK-ALCL, inducing remission and extending survival. However, further prospective studies with many patients are needed to determine the biological characteristics of this rare type of ALK-ALCL and relevant treatment strategies.

Investigation of underlying links between nitrogen transformation and microorganisms' network modularity in the novel static aerobic composting of dairy manure by "stepwise verification interaction analysis".

Conventional composting is a viable method treating agricultural solid waste, and microorganisms and nitrogen transformation are the two major components of this proces. Unfortunately, conventional composting is time-consuming and laborious, and limited efforts have been made to mitigate these problems. Herein, a novel static aerobic composting technology (NSACT) was developed and employed for the composting of cow manure and rice straw mixtures. During the composting process, physicochemical parameters were analyzed to evaluate the quality of compost products, and microbial abundance dynamics were determined using high-throughput sequencing technique. The results showed that NSACT achieved compost maturity within 17 days as the thermophilic stage (≥55 °C) lasted for 11 days. GI, pH, and C/N were 98.71 %, 8.38, and 19.67 in the top layer, 92.32 %, 8.24, and 22.38 in the middle layer, 102.08 %, 8.33, and 19.95 in the bottom layer. These observations indicate compost products maturated and met the requirements of current legislation. Compared with fungi, bacterial communities dominated NSACT composting system. Based on the stepwise verification interaction analysis (SVIA), the novel combination utilization of multiple statistical analyses (Spearman, RDA/CCA, Network modularity, and Path analyses), bacterial genera Norank Anaerolineaceae (-0.9279*), norank Gemmatimonadetes (1.1959*), norank Acidobacteria (0.6137**) and unclassified Proteobacteria (-0.7998*), and fungi genera Myriococcum thermophilum (-0.0445), unclassified Sordariales (-0.0828*), unclassified Lasiosphaeriaceae (-0.4174**), and Coprinopsis calospora (-0.3453*) were the identified key microbial taxa affecting NH4+-N, NO3--N, TKN and C/N transformation in the NSACT composting matrix respectively. This work revealed that NSACT successfully managed cow manure-rice straw wastes and significantly shorten the composting period. Interestingly, most microorganisms observed in this composting matrix acted in a synergistic manner, promoting nitrogen transformation.

Decreased hemodynamic response to fearful faces relative to neutral faces in the medial frontal cortex of first-episode drug-naïve major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a disabling disease with impaired recognition of emotional facial expressions. However, the evidence is heterogeneous, regarding the mechanism of emotional processing in MDD. Focusing on patients with first-episode drug-naïve MDD, we used functional near-infrared spectroscopy (fNIRS) to investigate whether MDD have characteristic patterns in cerebral activation under facial emotion recognition task (FERT). METHODS: Thirty-five patients with first-episode drug-naïve MDD and 39 healthy controls (HCs) underwent fNIRS measure to evaluate cerebral hemodynamic response in the frontal and temporal cortex during FERT. The 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale and Inventory of Depressive Symptomatology-Self Report were applied to assess the symptoms of the patients. Cognitive functions were assessed using THINC-integrated tool. RESULTS: Hypoactivation in the medial frontal was observed in patients with MDD during recognition of fearful faces relative to neutral faces (F-N faces). Specifically, we found more right lateralized activation in the medial frontal cortex among patients with MDD compared to HCs. Further, the medial frontal activation under the condition of F-N faces was positively correlated to scores of digit symbol substitution test, and negatively relative to severity of depressive symptoms in MDD group. LIMITATIONS: Our study is cross-sectional designed, and has a relatively small sample size. CONCLUSIONS: We found abnormal patterns in the medial frontal activation of patients with first-episode drug-naïve MDD in recognition of F-N faces, which correlates with performance in cognitive function and depressive symptoms.

Nanocarriers for the delivery of antibiotics into cells against intracellular bacterial infection.

The barrier function of host cells enables intracellular bacteria to evade the lethality of the host immune system and antibiotics, thereby causing chronic and recurrent infections that seriously threaten human health. Currently, the main clinical strategy for the treatment of intracellular bacterial infections involves the use of long-term and high-dose antibiotics. However, insufficient intracellular delivery of antibiotics along with various resistance mechanisms not only weakens the efficacy of current therapies but also causes serious adverse drug reactions, further increasing the disease and economic burden. Improving the delivery efficiency, intracellular accumulation, and action time of antibiotics remains the most economical and effective way to treat intracellular bacterial infections. The rapid development of nanotechnology provides a strategy to efficiently deliver antibiotics against intracellular bacterial infections into cells. In this review, we summarize the types of common intracellular pathogens, the difficulties faced by antibiotics in the treatment of intracellular bacterial infections, and the research progress of several types of representative nanocarriers for the delivery of antibiotics against intracellular bacterial infections that have emerged in recent years. This review is expected to provide a reference for further elucidating the intracellular transport mechanism of nanocarrier-drug complexes, designing safer and more effective nanocarriers and establishing new strategies against intracellular bacterial infection.

Deciphering biochar compost co-application impact on microbial communities mediating carbon and nitrogen transformation across different stages of corn development.

Under current climatic conditions, developing eco-friendly and climate-smart fertilizers has become increasingly important.The co-application of biochar and compost on agricultural soils has received considerable attention recently.Unfortunately, little is known about its effects on specific microbial taxa involved in carbon and nitrogen transformation in the soil.Herein, we report the efficacy of applying biochar-based amendments on soil physicochemical indices, enzymatic activity, functional genes, bacterial community, and their network patterns in corn rhizosphere at seedling (SS), flowering (FS), and maturity (MS) stages.The applied treatments were: compost alone (COM), biochar alone (BIOC), composted biochar (CMB), fortified compost (CMWB), and the control (no fertilizer (CNTRL).The non-metric multidimensional scaling (NMDS) indicated total nitrogen (TN), pH, NO3--N, urease, protease, and microbial biomass C (MBC) as the dominant environmental factors driving soil bacteria in this study.The dominant N mediating genes belonged to nitrate reductase (narG) and nitronate monooxygenase (amo), while beta-galactosidase, catalase, and alpha-amylase were the dominant genes observed relating to C cycling.Interestingly, the abundance of these genes was higher in COM, CMWB, and CMB compared with the CNTRL and BIOC treatments.The bacteria network properties of CWMB and CMB indicated robust niche overlap associated with high cross-feeding between bacterial communities compared to other treatments.Path and stepwise regression analyses revealed norank_Reyranellaceae and Sphingopyxis in CMWB as the major bacterial genera and the major predictive indices mediating soil organic C (SOC), NH4+-N, NO3--N, and TN transformation.Overall, biochar with compost amendments improved soil nutrient conditions, regulated the composition of the bacterial community, and benefited C/N cycling in the soil ecosystem.