Comparative analysis of supervised learning algorithms for prediction of cardiovascular diseases.

BACKGROUND: With the advent of artificial intelligence technology, machine learning algorithms have been widely used in the area of disease prediction. OBJECTIVE: Cardiovascular disease (CVD) seriously jeopardizes human health worldwide, thereby needing the establishment of an effective CVD prediction model that can be of great significance for controlling the risk of the disease and safeguarding the physical and mental health of the population. METHODS: Considering the UCI heart disease dataset as an example, initially, a single machine learning prediction model was constructed. Subsequently, six methods such as Pearson, chi-squared, RFE and LightGBM were comprehensively used for the feature screening. On the basis of the base classifiers, Soft Voting fusion and Stacking fusion was carried out to build a prediction model for cardiovascular diseases, in order to realize an early warning and disease intervention for high-risk populations. To address the data imbalance problem, the SMOTE method was adopted to process the data set, and the prediction effect of the model was analyzed using multi-dimensional and multi-indicators. RESULTS: In the single classifier model, the MLP algorithm performed optimally on the preprocessed heart disease dataset. After feature selection, five features eliminated. The ENSEM_SV algorithm that combines the base classifiers to determine the prediction results by soft voting on the results of the classifiers achieved the optimal value on five metrics such as Accuracy, Jaccard_Score, Hamm_Loss, AUC, etc., and the AUC value reached 0.951. The RF, ET, GBDT, and LGB algorithms were employed in the first stage sub-model composed of base classifiers. The AB algorithm was selected as the second stage model, and the ensemble algorithm ENSEM_ST, obtained by Stacking fusion of the two stages exhibited the best performance on 7 indicators such as Accuracy, Sensitivity, F1_Score, Mathew_Corrcoef, etc., and the AUC reached 0.952. Furthermore, a comparison of the algorithms' classification effects based on different training set occupancy was carried out. The results indicated that the prediction performance of both the fusion models was better than the single models, and the overall effect of ENSEM_ST fusion was stronger than the ENSEM_SV fusion. CONCLUSIONS: The fusion model established in this study improved the overall classification accuracy and stability of the model to a significant extent. It has a good application value in the predictive analysis of CVD diagnosis, and can provide a valuable reference in the disease diagnosis and intervention strategies.

Large-scale analysis of the ARF and Aux/IAA gene families in 406 horticultural and other plants.

The auxin response factor (ARF) and auxin/indole-3-acetic acid (Aux/IAA) family of genes are central components of the auxin signaling pathway and play essential roles in plant growth and development. Their large-scale analysis and evolutionary trajectory of origin are currently not known. Here, we identified the corresponding ARF and Aux/IAA family members and performed a large-scale analysis by scanning 406 plant genomes. The results showed that the ARF and Aux/IAA gene families originated from charophytes. The ARF family sequences were more conserved than the Aux/IAA family sequences. Dispersed duplications were the common expansion mode of ARF and Aux/IAA families in bryophytes, ferns, and gymnosperms; however, whole-genome duplication was the common expansion mode of the ARF and Aux/IAA families in basal angiosperms, magnoliids, monocots, and dicots. Expression and regulatory network analyses revealed that the Arabidopsis thaliana ARF and Aux/IAA families responded to multiple hormone, biotic, and abiotic stresses. The APETALA2 and serum response factor-transcription factor gene families were commonly enriched in the upstream and downstream genes of the ARF and Aux/IAA gene families. Our study provides a comprehensive overview of the evolutionary trajectories, structural functions, expansion mechanisms, expression patterns, and regulatory networks of these two gene families.

Zeb1-controlled metabolic plasticity enables remodeling of chromatin accessibility in the development of neuroendocrine prostate cancer.

Cell plasticity has been found to play a critical role in tumor progression and therapy resistance. However, our understanding of the characteristics and markers of plastic cellular states during cancer cell lineage transition remains limited. In this study, multi-omics analyses show that prostate cancer cells undergo an intermediate state marked by Zeb1 expression with epithelial-mesenchymal transition (EMT), stemness, and neuroendocrine features during the development of neuroendocrine prostate cancer (NEPC). Organoid-formation assays and in vivo lineage tracing experiments demonstrate that Zeb1+ epithelioid cells are putative cells of origin for NEPC. Mechanistically, Zeb1 transcriptionally regulates the expression of several key glycolytic enzymes, thereby predisposing tumor cells to utilize glycolysis for energy metabolism. During this process, lactate accumulation-mediated histone lactylation enhances chromatin accessibility and cellular plasticity including induction of neuro-gene expression, which promotes NEPC development. Collectively, Zeb1-driven metabolic rewiring enables the epigenetic reprogramming of prostate cancer cells to license the adeno-to-neuroendocrine lineage transition.

KCNH6 is essential for insulin secretion by regulating intracellular ER Ca2+ store.

Appropriate Ca2+ concentration in the endoplasmic reticulum (ER), modulating cytosolic Ca2+ signal, serves significant roles in physiological function of pancreatic ß cells. To maintaining ER homeostasis, Ca2+ movement across the ER membrane is always accompanied by a simultaneous K+ flux in the opposite direction. KCNH6 was proven to modulate insulin secretion by controlling plasma membrane action potential duration and intracellular Ca2+ influx. Meanwhile, the specific function of KCNH6 in pancreatic ß-cells remains unclear. In this study, we found that KCNH6 exhibited mainly ER localization and Kcnh6 ß-cell-specific knockout (ßKO) mice suffered from abnormal glucose tolerance and impaired insulin secretion in adulthood. ER Ca2+ store was overloaded in islets of ßKO mice, which contributed to ER stress and ER stress-induced apoptosis in ß cells. Next, we verified that ethanol treatment induced increases in ER Ca2+ store and apoptosis in pancreatic ß cells, whereas adenovirus-mediated KCNH6 overexpression in islets attenuated ethanol-induced ER stress and apoptosis. In addition, tail-vein injections of KCNH6 lentivirus rescued KCNH6 expression in ßKO mice, restored ER Ca2+ overload and attenuated ER stress in ß cells, which further confirms that KCNH6 protects islets from ER stress and apoptosis. These data suggest that KCNH6 on the ER membrane may help to stabilize intracellular ER Ca2+ stores and protect ß cells from ER stress and apoptosis. In conclusion, our study reveals the protective potential of KCNH6-targeting drugs in ER stress-induced diabetes.

Injectable Nano-in-Gel Vaccine for Spatial and Temporal Control of Vaccine Kinetics and Breast Cancer Postsurgical Therapy.

Breast cancer is the most commonly diagnosed cancer, and surgical resection is the first choice for its treatment. With the development of operation techniques, surgical treatment for breast cancer is evolving toward minimally invasive and breast-conserving approaches. However, breast-conserving surgery is prone to an increased risk of cancer recurrence and is becoming a key challenge that needs to be solved. In this study, we introduce a one-shot injectable nano-in-gel vaccine (NIGel-Vax) for postoperative breast cancer therapy. The NIGel-Vax was constructed by mixing protein antigens with PEI-4BImi-Man adjuvant and then encapsulated in a hydrogel made with oxidized dextran (ODEX) and 4-arm PEG-ONH2. Using 4T1 tumor-extracted proteins as antigen, the NIGel-Vax achieved a 92% tumor suppression rate and a 33% cure rate as a postoperative therapy in the 4T1 tumor model. Using the tumor-associated antigen trophoblast cell-surface antigen 2 (TROP2) protein as the antigen, NIGel-Vax achieved a 96% tumor suppression rate and a 50% cure rate in triple-negative breast cancer (TNBC) models. This design provides an encouraging approach for breast cancer postoperative management.

All-potassium channel CRISPR screening reveals a lysine-specific pathway of insulin secretion.

OBJECTIVE: Genome-scale CRISPR-Cas9 knockout coupled with single-cell RNA sequencing (scRNA-seq) has been used to identify function-related genes. However, this method may knock out too many genes, leading to low efficiency in finding genes of interest. Insulin secretion is controlled by several electrophysiological events, including fluxes of KATP depolarization and K+ repolarization. It is well known that glucose stimulates insulin secretion from pancreatic ß-cells, mainly via the KATP depolarization channel, but whether other nutrients directly regulate the repolarization K+ channel to promote insulin secretion is unknown. METHODS: We used a system involving CRISPR-Cas9-mediated knockout of all 83 K+ channels and scRNA-seq in a pancreatic ß cell line to identify genes associated with insulin secretion. RESULTS: The expression levels of insulin genes were significantly increased after all-K+ channel knockout. Furthermore, Kcnb1 and Kcnh6 were the two most important repolarization K+ channels for the increase in high-glucose-dependent insulin secretion that occurred upon application of specific inhibitors of the channels. Kcnh6 currents, but not Kcnb1 currents, were reduced by one of the amino acids, lysine, in both transfected cells, primary cells and mice with ß-cell-specific deletion of Kcnh6. CONCLUSIONS: Our function-related CRISPR screen with scRNA-seq identifies Kcnh6 as a lysine-specific channel.

Enhanced sequestration of Pb2+ and Cu2+ by Artemia cyst shell supported nano-Mg composite and the potential photocatalytic performance of carbonized exhausted-adsorbent.

This study reported a new strategy for enhanced Pb2+ and Cu2+ sequestration by Artemia cyst shell (shell) supported nano-Mg from aqueous solutions and the carbonated exhausted-adsorbents sequenced potential application in photo-catalyst, which obtained two expected results. One is that the immobilization of nano-Mg onto Artemia cyst shell (shell-Mg) can greatly strengthen the adsorption effect of the neat cyst shell on Pb2+ and Cu2+. The adsorption capacities of shell-Mg for both metal ions reached to 622.01 and 313.91 mg/g, which was 10-15 and 30-50 times that of the neat shell respectively. And shell-Mg has strong selectivity, which was approximately 2-4 times that of shell. The shell-Mg can be used to retrieve Pb2+ and Cu2+ from aqueous solutions efficiently. Another is that the carbonated exhausted-adsorbents (C-shell-Mg-Pb and C-shell-Mg-Cu) showed their potential photocatalytic degradation effects on congo red under pH = 4 condition, the decolorization rate reached to 61.19% and 80.39% respectively. Reuse of exhausted adsorbents can avoid the secondary pollution caused by the regeneration, extend the utilization value of exhausted adsorbents, and provide a new viewpoint for the reuse of spent bio-nanomaterial adsorbents.

Enhancing humification and microbial interactions during co-composting of pig manure and wine grape pomace: The role of biochar and Fe2O3.

Phenol-rich wine grape pomace (WGP) improves the conversion of pig manure (PM) into humic acid (HA) during composting. However, the impact of using combinations of Fe2O3 and biochar known to promote compost maturation remains uncertain. This research explored the individual and combined influence of biochar and Fe2O3 during the co-composting of PM and WGP. The findings revealed that Fe2O3 boosts microbial network symbiosis (3233 links), augments the HA yield to 3.38 by promoting polysaccharide C-O stretching, and improves the germination index to 124.82 %. Limited microbial interactions, increased by biochar, resulted in a lower HA yield (2.50). However, the combination weakened the stretching of aromatics and quinones, which contribute to the formation of HA, resulting in reduced the humification to 2.73. In addition, Bacillus and Actinomadura were identified as pivotal factors affecting HA content. This study highlights Fe2O3 and biochar's roles in phenol-rich compost humification, but combined use reduces efficacy.

Footsteps detection and identification based on distributed optical fiber sensor and double-YOLO model.

A footstep detection and recognition method based on distributed optical fiber sensor and double-YOLO method is proposed. The sound of footsteps is detected by a phase-sensitive optical time-domain reflectometry (Φ-OTDR) and the footsteps are located and identified by double-YOLO method. The Φ-OTDR can cover a much larger sensing range than traditional sensors. Based on the stride and step frequency of the gait, the double-YOLO method can determine the walker's ID. Primary field experiment results show that this method can detect, locate and identify the footsteps of three persons, and achieve about 86.0% identification accuracy, with 12.6% accuracy improvement compared to single-YOLO method. This footstep detection and recognition method may promote the development of gait-based clinical diagnosis or person identification application.

ADORA2A-driven proline synthesis triggers epigenetic reprogramming in neuroendocrine prostate and lung cancers.

Cell lineage plasticity is one of the major causes for the failure of targeted therapies in various cancers. However, the driver and actionable drug targets in promoting cancer cell lineage plasticity are scarcely identified. Here, we found that a G protein-coupled receptor, ADORA2A, is specifically upregulated during neuroendocrine differentiation, a common form of lineage plasticity in prostate cancer and lung cancer following targeted therapies. Activation of the ADORA2A signaling rewires the proline metabolism via an ERK/MYC/PYCR cascade. Increased proline synthesis promotes deacetylases SIRT6/7-mediated deacetylation of histone H3 at lysine 27 (H3K27), and thereby biases a global transcriptional output toward a neuroendocrine lineage profile. Ablation of Adora2a in genetically engineered mouse models inhibits the development and progression of neuroendocrine prostate and lung cancers, and, intriguingly, prevents the adenocarcinoma-to-neuroendocrine phenotypic transition. Importantly, pharmacological blockade of ADORA2A profoundly represses neuroendocrine prostate and lung cancer growth in vivo. Therefore, we believe that ADORA2A can be used as a promising therapeutic target to govern the epigenetic reprogramming in neuroendocrine malignancies.

Observing Liquid Sloshing Based on a Multi-Degree-of-Freedom Pendulum Model and Free Surface Fluctuation Sensor.

Rollover prevention of partially filled tank trucks is an ongoing challenge in the road transportation industry, with the core challenge being real-time perception and observation of the liquid state inside the tank. In order to realize reliable observation of a sloshing liquid, this article first proposes a sloshing modeling method based on a multi-degree-of-freedom pendulum model and derives the double mass trammel pendulum model (DMTP, 2DOF) accordingly, which accurately reflects the sloshing dynamics under wider operating conditions. Second, a free surface fluctuation sensor is designed based on magnetostriction, capable of measuring the inclination and height of the liquid level inside tanks filled with hazardous chemicals. Finally, the unscented Kalman filter (UKF) is utilized to synthesize the information of the two, establishing a credible real-time observation of the sloshing liquid. Verified using a vehicle-fluid coupled co-simulation, under the condition of a consecutive double lane change, the observation error of the proposed method is only 25.9% of that of the open-loop calculation, providing a secure guarantee for the observation of the state variables of the single pendulum model (SP) used for most kinds of anti-rollover control.

DNA methylation-dependent epigenetic regulation of Verticillium dahliae virulence in plants.

As a conserved epigenetic mark, DNA cytosine methylation, at the 5' position (5-mC), plays important roles in multiple biological processes, including plant immunity. However, the involvement of DNA methylation in the determinants of virulence of phytopathogenic fungi remains elusive. In this study, we profiled the DNA methylation patterns of the phytopathogenic fungus Verticillium dahliae, one of the major causal pathogens of Verticillium wilt disease that causes great losses in many crops, and explored its contribution in fungal pathogenicity. We reveal that DNA methylation modification is present in V. dahliae and is required for its full virulence in host plants. The major enzymes responsible for the establishment of DNA methylation in V. dahliae were identified. We provided evidence that DNA methyltransferase-mediated establishment of DNA methylation pattern positively regulates fungal virulence, mainly through repressing a conserved protein kinase VdRim15-mediated Ca2+ signaling and ROS production, which is essential for the penetration activity of V. dahliae. In addition, we further demonstrated that histone H3 lysine 9 trimethylation (H3K9me3), another heterochromatin marker that is closely associated with 5-mC in eukaryotes, also participates in the regulation of V. dahliae pathogenicity, through a similar mechanism. More importantly, DNA methyltransferase genes VdRid, VdDnmt5, as well as H3K9me3 methyltransferase genes, were greatly induced during the early infection phase, implying that a dynamic regulation of 5-mC and H3K9me3 homeostasis is required for an efficient infection. Collectively, our findings uncover an epigenetic mechanism in the regulation of phytopathogenic fungal virulence. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00117-5.

Synergistic effect triggered by Fe2O3 and oxygen-induced hydroxyl radical enhances formation of amino-phenolic humic-like substance.

Metal oxides play a promising role in the transformation of polyphenols and amino acids involved in naturally occurring humification. The objective of this study was to explore the synergistic interactions between Fe2O3 and O2 in the formation of humic substances under a controlled O2 atmosphere (0%, 21% and 40% O2 levels). The results indicate that an O2 level of 21% with Fe2O3 was optimal for humic acid (HA) production. Hydroxyl radicals (∙OH) formed and promoted the formation of HA in the presence of O2, and O2 improved the enhancing capacity of Fe2O3 by oxidizing Fe(II) to Fe(III). Moreover, the combination of these processes resulted in a synergistic improvement in humification. The evolution of functional groups in HA suggested that O2 promoted the formation of oxygen-containing groups such as lipids, and Fe2O3 was conducive to the formation of dark-coloured polymers during the darkening process of humification. Furthermore, the O2 level of 40% inhibited the formation of HA by reducing the transformation from Fe(III) to Fe(II). The XRD results showed few changes in the composition of Fe2O3 before and after humification, which indicated that Fe2O3 was a catalyst and an oxidant. The heterospectral UV-Vis/FTIR results suggested that ∙OH attacked phenolic rings to form the aromatic ring skeleton of HA and benefit the ring-opening copolymerization of humic precursors. In addition, structural equation modelling demonstrated that dissolved Fe was the key parameter affecting the HA yield. These findings provide new insights into the synergism of O2-mediated ∙OH production associated with metal oxide-facilitated humification.

When "looking at nothing" imparts something: Retrospective gaze cues flexibly direct prioritization in visual working memory.

Previous research has shown that retrospective gaze cues direct attention to internally maintained representations in visual working memory (vWM). Here, we aimed to differentiate the dual nature of gaze and accordingly proposed two hypotheses regarding the gaze-induced prioritization in vWM. The directional cueing hypothesis claims a constant attentional shifting to the gazed-at direction. By contrast, the referential cueing hypothesis proposes that gaze cues selectively orient attention toward their referents. To test these hypotheses, we employed an adapted change-detection task wherein gaze cues were presented during the retention interval. Critically, the cue character was positioned between two barriers, which could be either opaque (the blocked condition) or transparent (the unblocked condition). Polygons previously presented at the gazed-at (vs. gazed-away) location were better memorized, but not when the visual perspective of the character was obstructed (i.e., the blocked condition, Experiment 1). Subsequent experiments demonstrated that physical motion cues (Experiment 2) and inverted face cues (Experiment 3), which disrupted the extraction of referential signals, were immune to barrier settings. In Experiment 4, we generalize this selective cueing effect to faces with fearful expressions. These consistent findings support the referential cueing hypothesis and emphasize the distinctiveness of social attention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Bipolaronic Nature of the Pseudogap in Quasi-One-Dimensional (TaSe4)2I Revealed via Weak Photoexcitation.

The origin of the pseudogap in many strongly correlated materials has been a longstanding puzzle. Here, we present experimental evidence that many-body interactions among small Holstein polarons, i.e., the formation of bipolarons, are primarily responsible for the pseudogap in (TaSe4)2I. After weak photoexcitation of the material, we observe the appearance of both dispersive (single-particle bare band) and flat bands (single-polaron sub-bands) in the gap by using time- and angle-resolved photoemission spectroscopy. Based on Monte Carlo simulations of the Holstein model, we propose that the melting of pseudogap and emergence of new bands originate from a bipolaron to single-polaron crossover. We also observe dramatically different relaxation times for the excited in-gap states in (TaSe4)2I (∼600 fs) compared with another 1D material Rb0.3MoO3 (∼60 fs), which provides a new method for distinguishing between pseudogaps induced by polaronic or Luttinger-liquid many-body interactions.

Phosphorylation at tyrosine 317 and 508 are crucial for PIK3CA/p110α to promote CRC tumorigenesis.

BACKGROUND: PI3K/AKT signaling pathway plays important role in tumorigenesis of human cancer. Protein phosphorylation is crucial for signaling transduction of this pathway. PIK3CA, encoding the catalytic subunit p110α of PI3K complex, is one of the most frequently mutated oncogenes in human cancers. However, phosphorylation sites of PIK3CA/p110α and their underlying mechanism in tumorigenesis are largely unknown. METHODS: Tyrosine phosphorylation sites of PIK3CA/p110α are identified with Mass-Spectrum. Crispr/CAS9 strategy is applied to generate Y317F and Y508F mutant knock-in cell clones. The growth and metastasis abilities of cells are evaluated in vitro and in vivo. Phospho-proteomics analysis and Western blots are used to demonstrate downstream signaling pathways of PIK3CA/p110α tyrosine phosphorylation. In vitro kinase assay is applied to identify the kinase of PIK3CA/p110α tyrosine phosphorylation. RESULTS: Tyrosine phosphorylation of PIK3CA/p110α is stimulated by growth factors such as EGF, HGF and PDGF. Two tyrosine residues, Y317 and Y508, are identified on PIK3CA/p110α. Either Y317 or Y508 phosphorylation is essential for tumorigenesis of CRC. Mutation at Y317 of p110α reduces the proliferation, migration, and invasion of cancer cells through Src-MLC2 pathway, while mutation at Y508 of p110α impairs AKT signaling. Moreover, Src interacts with and phosphorylates p110α. CONCLUSIONS: PIK3CA/p110α phosphorylation at Y317 and Y508 play important role in tumorigenesis of colorectal cancer through two independent pathways.

Magnetic Domains and Their Power Spectral Densities in Non-Oriented Electrical Steel after Thermal Compression at Different Rates.

The magnetic domains of non-oriented electrical steel bearing cumulative thermal compressions made by a Gleeble 3500 Thermal System were observed using an atomic force microscope (AFM). The component forces, comprising the magnetic forces between the AFM probe and magnetic domains of the samples, along the freedom direction of the probe, were measured, and they formed the value fluctuation of the magnetic domains. The fluctuations of the magnetic domains were analyzed by examining the power spectral density (PSD) curves. The hysteresis curves of the samples were measured using a highly sensitive magnetic measurement system. An analysis of the magnetic force microscope (MFM) maps suggested that some magnetic domains were compressed into crushed and fragmented shapes, similar to the microstructure of deformed grains. Meanwhile, some were reconstructed within the thermal compressions, like dynamic recrystallization microstructures. Meaningfully, the MFM probe moved and deformed the proximal magnetic domains of tested samples within the region of its weak magnetic field. The peak positions of the magnetic domains with a high deformation rate were shifted and moved during the measuring processes by the weakly polarized probe. Both windward and leeward sides simultaneously expressed a slope towards each co-adjacent valley in the MFM maps and induced a statistical throbbing within a narrow band in the PSD curves. Thus, the MFM scanning mode was also analyzed and improved to obtain accurate MFM maps with low disturbances from the weak magnetic field of the probe. Swapping the order positions of the middle processes in the MFM scanning and adding a gliding step between them could offset the peak skewing of magnetic domains caused by the weakly polarized probe during MFM measurement process without incurring excessive replacement costs. Accumulative compression at a high rate (10 s-1) would crush magnetic domains into irregularly decreasing sizes with messy boundaries. This investigation provides an example of the complete relationships among deformations, magnetic domains, and magnetic properties.

Conformal in-ear bioelectronics for visual and auditory brain-computer interfaces.

Brain-computer interfaces (BCIs) have attracted considerable attention in motor and language rehabilitation. Most devices use cap-based non-invasive, headband-based commercial products or microneedle-based invasive approaches, which are constrained for inconvenience, limited applications, inflammation risks and even irreversible damage to soft tissues. Here, we propose in-ear visual and auditory BCIs based on in-ear bioelectronics, named as SpiralE, which can adaptively expand and spiral along the auditory meatus under electrothermal actuation to ensure conformal contact. Participants achieve offline accuracies of 95% in 9-target steady state visual evoked potential (SSVEP) BCI classification and type target phrases successfully in a calibration-free 40-target online SSVEP speller experiment. Interestingly, in-ear SSVEPs exhibit significant 2nd harmonic tendencies, indicating that in-ear sensing may be complementary for studying harmonic spatial distributions in SSVEP studies. Moreover, natural speech auditory classification accuracy can reach 84% in cocktail party experiments. The SpiralE provides innovative concepts for designing 3D flexible bioelectronics and assists the development of biomedical engineering and neural monitoring.

Gut microbiota modulate distal symmetric polyneuropathy in patients with diabetes.

The pathogenic mechanisms underlying distal symmetric polyneuropathy (DSPN), a common neuropathy in patients with diabetes mellitus (DM), are not fully understood. Here, we discover that the gut microbiota from patients with DSPN can induce a phenotype exhibiting more severe peripheral neuropathy in db/db mice. In a randomized, double-blind, and placebo-controlled trial (ChiCTR1800017257), compared to 10 patients who received placebo, DSPN was significantly alleviated in the 22 patients who received fecal microbiota transplants from healthy donors, independent of glycemic control. The gut bacterial genomes that correlated with the Toronto Clinical Scoring System (TCSS) score were organized in two competing guilds. Increased guild 1, which had higher capacity in butyrate production, and decreased guild 2, which harbored more genes in synthetic pathway of endotoxin, were associated with improved gut barrier integrity and decreased proinflammatory cytokine levels. Moreover, matched enterotype between transplants and recipients showed better therapeutic efficacy with more enriched guild 1 and suppressed guild 2. Thus, changes in these two competing guilds may play a causative role in DSPN and have the potential for therapeutic targeting.