New techniques to identify the tissue of origin for cancer of unknown primary in the era of precision medicine: progress and challenges.

Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.

An innovative immunotherapeutic strategy for rheumatoid arthritis: Selectively suppressing angiogenesis and osteoclast differentiation by fully human antibody targeting thymocyte antigen-1.

Thymocyte antigen-1 (THY-1)is a potential target for rheumatoid arthritis (RA) treatment, and THY-1 positive fibroblast-like synoviocytes (FLS) are enriched in the synovium of RA patients and participate in angiogenesis to accelerate RA progression. In this study, we screened an antibody targeting THY-1 (THY-1 Ab) and explored its mechanism in alleviating RA progression. THY-1 Ab was screened from ScFv phage antibody library by phage display technology (PDT). THY-1 Ab-treated collagen induced arthritis (CIA) mice had lower degree of arthritis scores. We explore the mechanism of THY-1 Ab in alleviating RA progression. THY-1 Ab can remarkably inhibit the secretion of pro-inflammatory factors and promote the secretion of anti-inflammatory factors. Further experiments showed that THY1 Ab downregulated the expression of JUNB by the hsa_circ_0094342/miRNA-155-5P/SPI1 axis, inhibited RA angiogenesis and osteoclast differentiation, and relieved RA progression. These findings support that THY-1 Ab is a promising therapeutic antibody for RA treatment.

New insights into syntrophic ethanol oxidation: Effects of operational modes and solids retention times.

Anaerobic ethanol oxidation relies on syntrophic interactions among functional microorganisms to become thermodynamically feasible. Different operational modes (sequencing batch reactors, SBRs, and continuous flow reactors, CFRs) and solids retention times (SRT, 25 days and 10 days) were employed in four ethanol-fed reactors, named as SBR25d, SBR10d, CFR25d, and CFR10d, respectively. System performance, syntrophic relationships, microbial communities, and metabolic pathways were examined. During the long-term operation, 2002.7 ± 56.0 mg COD/L acetate was accumulated in CFR10d due to the washout of acetotrophic methanogens. Microorganisms with high half-saturation constants were enriched in reactors of 25-day SRT. Moreover, ethanol oxidizing bacteria and acetotrophic methanogens with high half-saturation constants could be acclimated in SBRs. In SBRs, Syner-01 and Methanothrix dominated, and the low SRT of 10 days increased the relative abundance of Geobacter to 38.0%. In CFRs, the low SRT of 10 days resulted in an increase of Desulfovibrio among syntrophic bacteria, and CFR10d could be employed in enriching hydrogenotrophic methanogens like Methanobrevibacter.

Mechanistic understanding of acclimation and energy metabolism of acetoclastic methanogens under different substrate to microorganism ratios.

Mechanistic understanding of acetoclastic methanogenesis is pivotal for optimizing anaerobic digestion for efficient methane production. In this study, two different operational modes, continuous flow reactor (CFR) and sequencing batch reactor (SBR), accompanied with solids retention times (SRT) of 10 days (SBR10d and CFR10d) and 25 days (SBR25d and CFR25d) were implemented to elucidate their impacts on microbial communities and energy metabolism of methanogens in acetate-fed systems. Microbial community analysis revealed that the relative abundance of Methanosarcina (16.0%-46.0%) surpassed Methanothrix (3.7%-22.9%) in each reactor. SBRs had the potential to enrich both Methanothrix and Methanosarcina. Compared to SBRs, CFRs had lower total relative abundance of methanogens. Methanosarcina exhibited a superior enrichment in reactors with 10-day SRT, while Methanothrix preferred to be acclimated in reactors with 25-day SRT. The operational mode and SRT were also observed to affect the distribution of acetate-utilizing bacteria, including Pseudomonas, Desulfocurvus, Mesotoga, and Thauera. Regarding enzymes involved in energy metabolism, Ech and Vho/Vht demonstrated higher relative abundances at 10-day SRT compared to 25-day SRT, whereas Fpo and MtrA-H showed higher relative abundances in SBRs than those in CFRs. The relative abundance of genes encoding ATPase harbored by Methanothrix was higher than Methanosarcina at 25-day SRT. Additionally, the relative abundance of V/A-type ATPase (typically for methanogens) was observed higher in SBRs compared to CFRs, while the F-type ATPase (typically for bacteria) exhibited higher relative abundance in CFRs than that in SBRs.

Operational mode and powdered activated carbon promoting syntrophic propionate oxidation during anaerobic digestion of complex organic substances.

Operational mode and powdered activated carbon (PAC) are key factors facilitating microbial syntrophy and interspecies electron transfer during anaerobic digestion, consequently benefiting process stability and efficient methanogenesis. In this study, continuous-flow reactor (CFR) and sequencing batch reactor (SBR), with and without the addition of PAC, respectively, were operated to examine their effects on system performance and methanogenic activity. Based on the cycle-test result, the PAC-amended CFR (CFRPAC) recorded both the highest methane yield (690.1 mL/L) and the maximum CH4 production rate (28.8 mL/(L·h)), while SBRs exhibited slow methanogenic rates. However, activity assays indicated that SBRs were beneficial for organics removal in batch experiments fed with peptone. Taxonomic and functional analysis confirmed that CFRs were optimal for proliferating oligotrophs (e.g., Geobacter) and SBRs were more suitable for copiotrophs (e.g., Desulfobulbus). Metagenomic analysis revealed that CFRs had efficient acetate metabolic pathways from propionate and ethanol, whereas SBRs did not, resulting in the buildup of propionate. Furthermore, Methanobacterium and Methanothrix were acclimated to the different operational conditions, while acetoclastic Methanosarcina and hydrogenotrophic Methanolinea were acclimated in SBRs (5.1-13.4%) and CFRs (0.3-1.7%), respectively. This study confirmed the enhancement of microbial syntrophy by the addition of PAC as well as the acclimation of electroactive bacteria (e.g., Geobacter) with complex organic substances.

Dual isothermal amplification all-in-one approach for rapid and highly sensitive quantification of plasma circulating MYCN gene of neuroblastoma.

A dual isothermal amplification assay with dual fluorescence signal detection strategy, named dual isothermal amplification all-in-one approach, was developed for rapid, one-step, highly sensitive quantification of plasma circulating MYCN copy number of neuroblastoma (NB). The developed strategy consisted of rolling circle amplification (RCA) and loop-mediated isothermal amplification (LAMP) on a real-time PCR system using highly specific probe, molecular beacon (MB), as detection probe. The developed strategy possessing a broad linear dynamic range of 10 aM to 1 pM for both target gene (MYCN) and reference gene (NAGK). The ratio of the MYCN copy number to NAGK copy number (M/N ratio) was detected by the developed approach in cell lines, NB tumor tissues, hepatoblastoma tumor tissues and Wilms' tumor tissues, to which the M/N ratios were consistent with previous reports. In particular, the M/N ratio in NB clinical tissue specimens and NB plasma specimens detected with the developed approach were in keeping with the standard RT-PCR approach. More importantly, the M/N ratio in NB tissue samples and corresponding plasma samples of NB patients were consistent with each other with a correlation coefficient of 0.9690, indicating that plasma circulating MYCN is a promising indicator for the risk classification of NB.

[Impact of mild hypothermia therapy on hemodynamics during the induction stage in neonates with moderate to severe hypoxic-ischemic encephalopathy].

OBJECTIVE: To study the changes in hemodynamics during the induction stage of systemic mild hypothermia therapy in neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE). METHODS: A total of 21 neonates with HIE who underwent systemic mild hypothermia therapy in the Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from July 2017 to April 2020 were enrolled. The rectal temperature of the neonates was lowered to 34℃ after 1-2 hours of induction and maintained at this level for 72 hours using a hypothermia blanket. The impedance method was used for noninvasive hemodynamic monitoring, and the changes in heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) from the start of hypothermia induction to the achievement of target rectal temperature (34℃). Blood lactic acid (LAC) and resistance index (RI) of the middle cerebral artery were recorded simultaneously. RESULTS: The 21 neonates with HIE had a mean gestational age of (39.6±1.1) weeks, a mean birth weight of (3 439±517) g, and a mean 5-minute Apgar score of 6.8±2.0. From the start of hypothermia induction to the achievement of target rectal temperature (34℃), there were significant reductions in HR, CO, and CI (P < 0.05), while there was no significant change in SV and MAP (P > 0.05). There was a significant increase in TPR (P < 0.05) and a significant reduction in LAC (P < 0.05), while there was no significant change in RI (P > 0.05). CONCLUSIONS: The systemic mild hypothermia therapy may have a significant impact on hemodynamics in neonates with moderate to severe HIE, and continuous hemodynamic monitoring is required during the treatment.

Flagellar motility mediates early-stage biofilm formation in oligotrophic aquatic environment.

Flagellar motility enables resource acquisition and noxious substance evasion, underpinning imperative ecological processes in aquatic environments. Yet the underlying mechanism that links flagellar motility with surface attachment and thereby biofilm formation, especially in conditions of limited resource availability, remains elusive. Here, we present experimental and modeling evidence to unveil bacterial motility and biofilm formation under nutrient-limited stresses with Pseudomonas aeruginosa (WT) and its nonflagellated isogenic mutant (ΔfliC) as model bacteria. Results revealed that boosted flagellar motility of WT strain promoted biofilm initialization to a peak value of 0.99 × 107 cells/cm2 at 1/50 dilution after 20 min incubation. We hypothesized that bacteria can invoke instant motility acceleration for survival confronting nutrient-limited stress, accompanied by optimized chemotactic foraging through sensing ambient chemical gradients. Accordingly, accelerated cell motility in oligotrophic environment created increased cell-cell and cell-surface interactions and thereof facilitated biofilm initialization. It was confirmed by the consistence of modeling predictions and experimental results of cell velocity and surface attachment. With the development of biofilm, promotion effect of flagellar motility responding to nutrient deprivation-stress faded out. Instead, loss of motility profiting increased growth rates and extracellular protein excretion, associated with an enhancement of biofilm development for the mutant in oligotrophic aquatic environment. For both strains, nutrient limitation evidently reduced planktonic cell propagation as expected. Our results offer new insights into the mechanical understanding of biofilm formation shaped by environmental stresses and associating biological responses.

Analysis of the Azimuth Ambiguity and Imaging Area Restriction for Circular SAR Based on the Back-Projection Algorithm.

Circular synthetic aperture radar (CSAR) has a 360° observation capability on the central observation scenario. A typical way to process CSAR imaging is to cut data into small sub-apertures because most targets are only coherent at a very small observation angle. There are many sub-aperture imaging methods after development in recent years. The back-projection algorithm is widely used because it is simple and can be applied to an arbitrary trajectory. Because of the limitation of the Nyquist sampling frequency and influence of the antenna sidelobe, azimuth ambiguity is a phenomenon that may occur in the radar imaging process. The existing researches typically choose the back-projection (BP) imaging area according to the SAR platform flight path and the antenna beam width. The limitation of the CSAR imaging area and its azimuth ambiguity region are rarely analyzed theoretically. This paper focus on the sub-aperture imaging of CSAR, based on the BP algorithm, which derives the relationship of azimuth ambiguity with CSAR parameters such as the pause repeat frequency (PRF), slant range angle, velocity of radar platform, etc. This paper proposes an equation for the calculation of the azimuth ambiguity region and analyzes the limitations, which provides theoretical support for CSAR parameter design, imaging area selection, and azimuth ambiguity analysis.

Powdered activated carbon facilitated degradation of complex organic compounds and tetracycline in stressed anaerobic digestion systems.

Tetracycline exerts an inhibitory effect on anaerobic digestion, inducing stressed microbial activities and even system failure. Continuous-flow reactors (CFRs) and sequencing batch reactors (SBRs) were employed along with the dosage of powdered activated carbon (PAC) to enhance tetracycline removal during anaerobic digestion of complex organic compounds. PAC increased the maximum methane production rate by 15.6% (CFRs) and 13.8% (SBRs), and tetracycline biodegradation by 24.4% (CFRs) and 19.2% (SBRs). CFRs showed higher tetracycline removal and methane production rates than SBRs. Geobacter was enriched in CFRs, where Methanothrix was enriched with the addition of PAC. Desulfomicrobium harbored abundant propionate degradation-related genes, significantly correlating with tetracycline removal. The genes encoding carbon dioxide reduction in Methanothrix along with the detection of Geobacter might indicate direct interspecies electron transfer for methanogenesis in CFRs and PAC-added reactors. The study offers new insights into anaerobic digestion under tetracycline-stressed conditions and strategies for optimizing tetracycline removal.

Prognostic analysis of related factors of adverse reactions to immunotherapy in advanced gastric cancer and establishment of a nomogram model.

BACKGROUND: Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years. However, the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study. In order to determine the association between adverse reaction factors and prognosis, the aim of this study was to conduct a systematic prognostic analysis. By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy, a nomogram model will be established to predict the survival status of patients more accurately. AIM: To explore the characteristics and predictors of immune-related adverse reactions (irAEs) in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1 (PD-1) inhibitors and to analyze the correlation between irAEs and patient prognosis. METHODS: A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected. Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred. Clinical features, manifestations, and prognosis of irAEs in the two groups were collected and analyzed. A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs, and the prediction model of irAEs was established. The receiver operating characteristic (ROC) curve was used to evaluate the ability of different indicators to predict irAEs. A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis. The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients. RESULTS: A total of 132 patients were followed up, of whom 63 (47.7%) developed irAEs. We looked at the two groups' clinical features and found that the two groups were statistically different in age ≥ 65 years, Ki-67 index, white blood cell count, neutrophil count, and regulatory T cell (Treg) count (all P < 0.05). Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence (P = 0.030). The ROC curve indicated that Treg + Ki-67 + age (≥ 65 years) combined could predict irAEs well (area under the curve = 0.753, 95% confidence interval: 0.623-0.848, P = 0.001). Results of the Kaplan-Meier survival curve showed that progression-free survival (PFS) was longer in the irAEs group than in the non-irAEs group (P = 0.001). Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS (P = 0.006). CONCLUSION: The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy. irAEs can affect the patients' PFS and result in longer PFS. Treg + Ki-67 + age (≥ 65 years old) combined can better predict the occurrence of adverse reactions.

Deciphering anaerobic ethanol metabolic pathways shaped by operational modes.

Efficient anaerobic digestion requires the syntrophic cooperation among diverse microorganisms with various metabolic pathways. In this study, two operational modes, i.e., the sequencing batch reactor (SBR) and the continuous-flow reactor (CFR), were adopted in ethanol-fed systems with or without the supplement of powdered activated carbon (PAC) to examine their effects on ethanol metabolic pathways. Notably, the operational mode of SBR and the presence of CO2 facilitated ethanol metabolism towards propionate production. This was further evidenced by the dominance of Desulfobulbus, and the increased relative abundances of enzymes (EC: 1.2.7.1 and 1.2.7.11) involved in CO2 metabolism in SBRs. Moreover, SBRs exhibited superior biomass-based rates of ethanol degradation and methanogenesis, surpassing those in CFRs by 53.1% and 22.3%, respectively. Remarkably, CFRs with the extended solids retention time enriched high relative abundances of Geobacter of 71.7% and 70.4% under conditions with and without the addition of PAC, respectively. Although both long-term and short-term PAC additions led to the increased sludge conductivity and a reduced methanogenic lag phase, only the long-term PAC addition resulted in enhanced rates of ethanol degradation and propionate production/degradation. The strategies by adjusting operational mode and PAC addition could be adopted for modulating the anaerobic ethanol metabolic pathway and enriching Geobacter.

Point-of-care ultrasound in early diagnosis and monitoring of deep abscess in newborns: a case report of two cases.

Objective: This study sought to analyze the value of point of care ultrasound (POCUS) in early diagnosis and monitoring of deep abscess in newborns. Methods: Retrospective analysis of the clinical data of two newborns admitted to the Neonatal Intensive Care Unit (NICU) of our hospital and diagnosed with deep abscess of the newborn. Combined with literature analysis, the value of POCUS in early diagnosis and monitoring of deep abscess of the newborn was evaluated. Results: The two newborns reported in this article were all admitted to NICU due to" "fever". POCUS was used to assist in early diagnosis of "liver abscess" and "lung abscess". Subsequently, POCUS was used to monitor lesion changes and adjust treatment plans. All patients were cured and discharged with a good prognosis. Conclusions: Deep abscesses in newborns are very rare and often life-threatening, but apart from fever, they often have no specific clinical manifestations and are easily misdiagnosed or missed. POCUS, as a bedside auxiliary examination tool, has high accuracy, radiation free, non-invasive, and convenient, and has high diagnostic and monitoring value in early diagnosis and monitoring of deep abscess in newborns.

The effect of tDCS on inhibitory control and its transfer effect on sustained attention in children with autism spectrum disorder: An fNIRS study.

BACKGROUND: Individuals with autism spectrum disorder (ASD) have inhibitory control deficits. The combination of transcranial direct current stimulation (tDCS) and inhibitory control training produces good transfer effects and improves neuroplasticity. However, no studies have explored whether applying tDCS over the dlPFC improves inhibitory control and produces transfer effects in children with ASD. OBJECTIVE: To explore whether multisession tDCS could enhance inhibitory control training (response inhibition), near-transfer (interference control) and far-transfer effects (sustained attention; stability of attention) in children with ASD and the generalizability of training effects in daily life and the class, as reflected by behavioral performance and neural activity measured by functional near-infrared spectroscopy (fNIRS). METHODS: Twenty-eight autistic children were randomly assigned to either the true or sham tDCS group. The experimental group received bifrontal tDCS stimulation at 1.5 mA, administered for 15 min daily across eight consecutive days. tDCS was delivered during a computerized Go/No-go training task. Behavioral performance in terms of inhibitory control (Dog/Monkey and Day/Night Stroop tasks), sustained attention (Continuous Performance and Cancellation tests), prefrontal cortex (PFC) neural activity and inhibitory control and sustained attention in the class and at home were evaluated. RESULTS: Training (response inhibition) and transfer effects (interference control; sustained attention) were significantly greater after receiving tDCS during the Go/No-go training task than after receiving sham tDCS. Changes in oxyhemoglobin (HbO) concentrations in the dlPFC and FPA associated with consistent conditions in the Day/Night Stroop and Continuous Performance test were observed after applying tDCS during the inhibitory control training task. Notably, transfer effects can be generalized to classroom environments. CONCLUSION: Inhibitory control training combined with tDCS may be a promising, safe, and effective method for improving inhibitory control and sustained attention in children with ASD.

Biliary atresia and cholestasis plasma non-targeted metabolomics unravels perturbed metabolic pathways and unveils a diagnostic model for biliary atresia.

The clinical diagnosis of biliary atresia (BA) poses challenges, particularly in distinguishing it from cholestasis (CS). Moreover, the prognosis for BA is unfavorable and there is a dearth of effective non-invasive diagnostic models for detection. Therefore, the aim of this study is to elucidate the metabolic disparities among children with BA, CS, and normal controls (NC) without any hepatic abnormalities through comprehensive metabolomics analysis. Additionally, our objective is to develop an advanced diagnostic model that enables identification of BA. The plasma samples from 90 children with BA, 48 children with CS, and 47 NC without any liver abnormalities children were subjected to metabolomics analysis, revealing significant differences in metabolite profiles among the 3 groups, particularly between BA and CS. A total of 238 differential metabolites were identified in the positive mode, while 89 differential metabolites were detected in the negative mode. Enrichment analysis revealed 10 distinct metabolic pathways that differed, such as lysine degradation, bile acid biosynthesis. A total of 18 biomarkers were identified through biomarker analysis, and in combination with the exploration of 3 additional biomarkers (LysoPC(18:2(9Z,12Z)), PC (22:5(7Z,10Z,13Z,16Z,19Z)/14:0), and Biliverdin-IX-α), a diagnostic model for BA was constructed using logistic regression analysis. The resulting ROC area under the curve was determined to be 0.968. This study presents an innovative and pioneering approach that utilizes metabolomics analysis to develop a diagnostic model for BA, thereby reducing the need for unnecessary invasive examinations and contributing to advancements in diagnosis and prognosis for patients with BA.

Genomic diversity, population structure, and genome-wide association reveal genetic differentiation and trait improvements in mango.

Mango (Mangifera indica L.) has been widely cultivated as a culturally and economically significant fruit tree for roughly 4000 years. Despite its rich history, little is known about the crop's domestication, genomic variation, and the genetic loci underlying agronomic traits. This study employs the whole-genome re-sequencing of 224 mango accessions sourced from 22 countries, with an average sequencing depth of 16.37×, to explore their genomic variation and diversity. Through phylogenomic analysis, M. himalis J.Y. Liang, a species grown in China, was reclassified into the cultivated mango group known as M. indica. Moreover, our investigation of mango population structure and differentiation revealed that Chinese accessions could be divided into two distinct gene pools, indicating the presence of independent genetic diversity ecotypes. By coupling genome-wide association studies with analyses of genotype variation patterns and expression patterns, we identified several candidate loci and dominant genotypes associated with mango flowering capability, fruit weight, and volatile compound production. In conclusion, our study offers valuable insights into the genetic differentiation of mango populations, paving the way for future agronomic improvements through genomic-assisted breeding.

Efficient Registration for Human Surfaces via Isometric Regularization on Embedded Deformation.

3D registration is a fundamental step to obtain the correspondences between surfaces. Traditional mesh alignment methods tackle this problem through non-rigid deformation, mostly accomplished by applying ICP-based (Iterative Closest Point) optimization. The embedded deformation method is proposed for the purpose of acceleration, which enables various real-time applications. However, it regularizes on an underlying simplified structure, which could be problematic for intricate cases when the simplified graph doesn't fully represent the surface attributes. Moreover, without elaborate parameter-tuning, deformation usually performs suboptimally, leading to slow convergence or a local minimum if all regions on the surface are assumed to share the same rigidity during the optimization. In this article, we propose a novel solution that decouples regularization from the underlying deformation model by explicitly managing the rigidity of vertex clusters. We further design an efficient two-step solution that alternates between isometric deformation and embedded deformation with cluster-based regularization. Our method can easily support region-adaptive regularization with cluster refinement and execute efficiently. Extensive experiments demonstrate the effectiveness of our approach for mesh alignment tasks even under large-scale deformation and imperfect data. Our method outperforms state-of-the-art methods both numerically and visually.

Metabolomics-transcriptomics joint analysis: unveiling the dysregulated cell death network and developing a diagnostic model for high-grade neuroblastoma.

High-grade neuroblastoma (HG-NB) exhibits a significantly diminished survival rate in comparison to low-grade neuroblastoma (LG-NB), primarily attributed to the mechanism of HG-NB is unclear and the lacking effective therapeutic targets and diagnostic model. Therefore, the current investigation aims to study the dysregulated network between HG-NB and LG-NB based on transcriptomics and metabolomics joint analysis. Meanwhile, a risk diagnostic model to distinguish HG-NB and LG-NB was also developed. Metabolomics analysis was conducted using plasma samples obtained from 48 HG-NB patients and 36 LG-NB patients. A total of 39 metabolites exhibited alterations, with 20 showing an increase and 19 displaying a decrease in HG-NB. Additionally, transcriptomics analysis was performed on NB tissue samples collected from 31 HG-NB patients and 20 LG-NB patients. Results showed that a significant alteration was observed in a total of 1,199 mRNAs in HG-NB, among which 893 were upregulated while the remaining 306 were downregulated. In particular, the joint analysis of both omics data revealed three aberrant pathways, namely the cAMP signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway, which were found to be associated with cell death. Notably, a diagnostic model for HG-NB risk classification was developed based on the genes MGST1, SERPINE1, and ERBB3 with an area under the receiver operating characteristic curve of 0.915. In the validation set, the sensitivity and specificity were determined to be 75.0% and 80.0%, respectively.

Nitrate removal in iron sulfide-driven autotrophic denitrification biofilter: Biochemical and chemical transformation pathways and its underlying microbial mechanism.

Iron sulfides-based autotrophic denitrification (IAD) is effective for treating nitrate-contaminated wastewater. However, the complex nitrate transformation pathways coupled with sulfur and iron cycles in IADs are still unclear. In this study, two columns (abiotic vs biotic) with iron sulfides (FeS) as the packing materials were constructed and operated continuously. In the abiotic column, FeS chemically reduced nitrate to ammonium under the ambient condition; this chemical reduction reaction pathway was spontaneous and has been overlooked in IAD reactors. In the biotic column (IAD biofilter), the complex nitrogen-transformation network was composed of chemical reduction, autotrophic denitrification, dissimilatory nitrate reduction to ammonium (DNRA) and sulfate reducing ammonium oxidation (Sulfammox). Metagenomic analysis and XPS characterization of the IAD biofilter further validated the roles of functional microbial communities (e.g., Acidovorax, Diaphorobacter, Desulfuromonas) in nitrate reduction process coupled with iron and sulfur cycles. This study gives an in-depth insight into the nitrogen transformations in IAD system and provides fundamental evidence about the underlying microbial mechanism for its further application in biological nitrogen removal.