A narrow-bandgap RuI3 nanoplatform to synergize radiotherapy, photothermal therapy, and thermoelectric dynamic therapy for tumor eradication.

Therapeutic resistance is an essential challenge for nanotherapeutics. Herein, a narrow bandgap RuI3 nanoplatform has been constructed firstly to synergize radiotherapy (RT), photothermal therapy (PTT), and thermoelectric dynamic therapy (TEDT) for tumor eradication. Specifically, the photothermal performance of RuI3 can ablate tumor cells while inducing TEDT. Noteworthy, the thermoelectric effect is found firstly in RuI3, which can spontaneously generate an electric field under the temperature gradient, prompting carrier separation and triggering massive ROS generation, thus aggravating oxidative stress level and effectively inhibiting HSP-90 expression. Moreover, RuI3 greatly enhances X-ray deposition owing to its high X-ray attenuation capacity, resulting in a pronounced computed tomography imaging contrast and DNA damage. In addition, RuI3 possesses both catalase-like and glutathione peroxidase-like properties, which alleviate tumor hypoxia and reduce antioxidant resistance, further exacerbating 1O2 production during RT and TEDT. This integrated therapy platform combining PTT, TEDT, and RT significantly inhibits tumor growth. STATEMENT OF SIGNIFICANCE: RuI3 nanoparticles were synthesized for the first time. RuI3 exhibited the highest photothermal properties among iodides, and the photothermal conversion efficiency was 53.38%. RuI3 was found to have a thermoelectric effect, and the power factor could be comparable to that of most conventional thermoelectric materials. RuI3 possessed both catalase-like and glutathione peroxidase-like properties, which contributed to enhancing the effect of radiotherapy.

Bimetallic Cu@Ru Core-Shell Structures with Ligand Effects for Endo-Exogenous Stimulation-Mediated Dynamic Oncotherapy.

Dynamic therapies, which induce reactive oxygen species (ROS) production in situ through endogenous and exogenous stimulation, are emerging as attractive options for tumor treatment. However, the complexity of the tumor substantially limits the efficacy of individual stimulus-triggered dynamic therapy. Herein, bimetallic copper and ruthenium (Cu@Ru) core-shell nanoparticles are applied for endo-exogenous stimulation-triggered dynamic therapy. The electronic structure of Cu@Ru is regulated through the ligand effects to improve the adsorption level for small molecules, such as water and oxygen. The core-shell heterojunction interface can rapidly separate electron-hole pairs generated by ultrasound and light stimulation, which initiate reactions with adsorbed small molecules, thus enhancing ROS generation. This synergistically complements tumor treatment together with ROS from endogenous stimulation. In vitro and in vivo experiments demonstrate that Cu@Ru nanoparticles can induce tumor cell apoptosis and ferroptosis through generated ROS. This study provides a new paradigm for endo-exogenous stimulation-based synergistic tumor treatment.

Gallbladder microbial species and host bile acids biosynthesis linked to cholesterol gallstone comparing to pigment individuals.

Gallstones are crystalline deposits in the gallbladder that are traditionally classified as cholesterol, pigment, or mixed stones based on their composition. Microbiota and host metabolism variances among the different types of gallstones remain largely unclear. Here, the bile and gallstone microbial species spectra of 29 subjects with gallstone disease (GSD, 24 cholesterol and 5 pigment) were revealed by type IIB restriction site-associated DNA microbiome sequencing (2bRAD-M). Among them (21 subjects: 18 cholesterol and 3 pigment), plasma samples were subjected to liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics. The microbiome yielded 896 species comprising 882 bacteria, 13 fungi, and 1 archaeon. Microbial profiling revealed significant enrichment of Cutibacterium acnes and Microbacterium sp005774735 in gallstone and Agrobacterium pusense and Enterovirga sp013044135 in the bile of cholesterol GSD subjects. The metabolome revealed 2296 metabolites, in which malvidin 3-(6''-malonylglucoside), 2-Methylpropyl glucosinolate, and ergothioneine were markedly enriched in cholesterol GSD subjects. Metabolite set enrichment analysis (MSEA) demonstrated enriched bile acids biosynthesis in individuals with cholesterol GSD. Overall, the multi-omics analysis revealed that microbiota and host metabolism interaction perturbations differ depending on the disease type. Perturbed gallstone type-related microbiota may contribute to unbalanced bile acids metabolism in the gallbladder and host, representing a potential early diagnostic marker and therapeutic target for GSD.

Glucose oxidase and ruthenium nanorods-embedded self-healing polyvinyl alcohol/polyethylene imine hydrogel for simultaneous photothermal/photodynamic/starvation therapy and skin reconstruction.

Tumor recurrence and wound healing represent significant burdens for tumor patients after the surgical removal of melanomas. Wound dressings with wound healing and anticancer therapeutic abilities could help to solve these issues. Thus, a hybrid hydrogel made of polyvinyl alcohol (PVA) and polyethylene imine (PEI) was prepared by cross-linking imine bond and boronic acid bond. This hydrogel was loaded with ruthenium nanorods (Ru NRs) and glucose oxidase (GOx) and named as nanocomposite hydrogel (Ru/GOx@Hydrogel), exhibiting remarkable photothermal/photodynamic/starvation antitumor therapy and wound repair abilities. Ru NRs are bifunctional phototherapeutic agents that simultaneously exhibit intrinsic photothermal and photodynamic functions. Three-dimensional composite hydrogel loaded with GOx can also consume glucose in the presence of O2 during tumor starvation therapy. Near-infrared (NIR) light-triggered hyperthermia can not only promote the consumption of glucose, but also facilitate the ablation of residual cancer cells. The antitumor effect of the Ru/GOx@Hydrogel resulted in significant improvements, compared to those observed with either phototherapy or starvation therapy alone. Additionally, the postoperative wound was substantially healed after treatment with Ru/GOx@Hydrogel and NIR irradiation. Therefore, the Ru/GOx@Hydrogel can be used as a multi-stimulus-responsive nanoplatform that could facilitate on-demand controlled drug release, and be used as a promising postoperative adjuvant in combination therapy.

"Spark" PtMnIr Nanozymes for Electrodynamic-Boosted Multienzymatic Tumor Immunotherapy.

Multienzyme-mimicking redox nanozymes capable of efficient reactive oxygen species (ROS) generation and cellular homeostasis disruption are highly pursued for cancer therapy. However, it still faces challenges from the complicate tumor microenvironment (TME) and high chance for tumor metastasis. Herein, well-dispersed PtMnIr nanozymes are designed with multiple enzymatic activities, including catalase (CAT), oxidase (OXD), superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GPx), which continuously produce ROS and deplete glutathione (GSH) concurrently in an "inner catalytic loop" way. With the help of electrodynamic stimulus, highly active "spark" species (Ir3+ and Mn3+) are significantly increased, resulting in an effective cascade enzymatic and electrodynamic therapy. Moreover, the cyclic generation of ROS can also facilitate ferroptosis and apoptosis in tumor cells, boosting synergistic therapy. Importantly, lung metastasis inhibition is found, which confirms efficient immunotherapy by the combined effect of immunogenic cell death (ICD) and Mn2+-induced cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (cGAS-STING) pathway, contributing great potential in the treatment of malignant tumors.

Dual enzyme-like Co-FeSe2 nanoflowers with GSH degradation capability for NIR II-enhanced catalytic tumor therapy.

Nanozymes mediated catalytic therapy can produce toxic reactive oxygen species (ROS) and destroy the metabolic balance of tumor cells, providing a new direction for cancer treatment. However, the catalytic efficiency of a single nanozyme is limited by the complexity of the tumor microenvironment (hypoxia, GSH overexpression, etc.). In order to overcome these problems, we designed flower-like Co-doped FeSe2 (Co-FeSe2) nanozymes by a simple wet chemistry method. Co-FeSe2 nanozymes not only exhibit high POD and OXD-mimicking activities for facile kinetics, but also effectively consume over-expressed glutathione (GSH), inhibiting the consumption of generated ROS and destroying the metabolic balance of the tumor microenvironment. These catalytic reactions trigger cell death through apoptosis and ferroptosis dual pathways. More importantly, under the NIR II laser irradiation, the catalytic activities of Co-FeSe2 nanozymes are boosted, confirming the photothermal and catalytic synergistic tumor therapy. This study takes advantage of self-cascading engineering that offers new ideas for designing efficient redox nanozymes and promoting their clinical translation.

Three Strategies in Engineering Nanomedicines for Tumor Microenvironment-Enabled Phototherapy.

Canonical phototherapeutics have several limitations, including a lack of tumor selectivity, nondiscriminatory phototoxicity, and tumor hypoxia aggravation. The tumor microenvironment (TME) is characterized by hypoxia, acidic pH, and high levels of H2 O2 , GSH, and proteases. To overcome the shortcomings of canonical phototherapy and achieve optimal theranostic effects with minimal side effects, unique TME characteristics are employed in the development of phototherapeutic nanomedicines. In this review, the effectiveness of three strategies for developing advanced phototherapeutics based on various TME characteristics is examined. The first strategy involves targeted delivery of phototherapeutics to tumors with the assistance of TME-induced nanoparticle disassembly or surface modification. The second strategy involves near-infrared absorption increase-induced phototherapy activation triggered by TME factors. The third strategy involves enhancing therapeutic efficacy by ameliorating TME. The functionalities, working principles, and significance of the three strategies for various applications are highlighted. Finally, possible challenges and future perspectives for further development are discussed.

Landscape in the gallbladder mycobiome and bacteriome of patients undergoing cholelithiasis with chronic cholecystitis.

Gallstone disease (GSD) is associated with changes in the gut and gallbladder bacterial composition, but there is limited information on the role of the fungal community (mycobiome) in disease development. This study aimed to characterize the gallbladder mycobiome profiles and their interactions with bacteriome in GSD. A total of 136 bile and gallstone samples (34 paired for bacteriome, and 33 paired and extra 2 bile samples for mycobiome) were obtained from calculi patients with chronic cholecystitis. Bile and gallstone bacteriome and mycobiome were profiled by 16S and internal transcribed spacer (ITS) rRNA gene sequencing, respectively. Gallbladder bacteriome, mycobiome, and interkingdom and intrakingdom interactions were compared between bile and gallstone. In general, microbial diversity was higher in bile than in gallstone, and distinct microbial community structures were observed among them. Deep Sea Euryarchaeotic Group, Rhodobacteraceae, and Rhodobacterales were microbial biomarkers of bile, while Clostridiales and Eubacterium coprostanoligenes were biomarkers of gallstone. Five fungal taxa, including Colletotrichum, Colletotrichum sublineola, and Epicoccum, were enriched in gallstone. Further ecologic analyses revealed that intensive transkingdom correlations between fungi and bacteria and intrakingdom correlations within them observed in gallstone were significantly decreased in bile. Large and complex fungal communities inhabit the gallbladder of patients with GSD. Gallstone, compared with bile, is characterized by significantly altered bacterial taxonomic composition and strengthened bacterial-bacterial, fungal-fungal, and bacterial-fungal correlations in the gallbladder of patients with GSD.

Palladium nanoparticle based smart hydrogels for NIR light-triggered photothermal/photodynamic therapy and drug release with wound healing capability.

Tumor recurrence and wound repair are two major challenges following cancer surgical resection that can be addressed through precision nanomedicine. Herein, palladium nanoparticles (Pd NPs) with photothermal and photodynamic therapy (PTT/PDT) capacity were successfully synthesized. The Pd NPs were loaded with chemotherapeutic doxorubicin (DOX) to form hydrogels (Pd/DOX@hydrogel) as a smart anti-tumor platform. The hydrogels were composed of clinically approved agarose and chitosan, with excellent biocompatibility and wound healing ability. Pd/DOX@hydrogel can be used for both PTT and PDT with a synergistic effect to kill tumor cells. Additionally, the photothermal effect of Pd/DOX@hydrogel allowed the photo-triggered drug release of DOX. Therefore, Pd/DOX@hydrogel can be used for near-infrared (NIR)-triggered PTT and PDT as well as for photo-induced chemotherapy, efficiently inhibiting tumor growth. Furthermore, Pd/DOX@hydrogel can be used as a temporary biomimetic skin to block the invasion of foreign harmful substances, promote angiogenesis, and accelerate wound repair and new skin formation. Thus, the as-prepared smart Pd/DOX@hydrogel is expected to provide a feasible therapeutic solution following tumor resection.

Pseudopyrolysis of Metal-Organic Frameworks: A Synchronous Nucleation Mechanism to Synthesize Ultrafine Metal Compound Nanoparticles.

Metal-Organic frameworks (MOFs) are increasingly being investigated for the synthesis of carbon-supported metal-based ultrafine nanoparticles (UNPs). However, the collapse of the carbon framework and aggregation of metal particles in the pyrolysis process have severely hindered their stability and applications. Here, we report the synchronous nucleation pseudopyrolysis of MOFs to confine Fe/FeOx UNPs in intact porous carbon nanorods (IPCNs), revealed by in situ transmission electron microscopy experiments and ex situ structure analysis. The pseudopyrolysis mechanism enables strong physical and chemical confinement effects between UNPs and carbon by moderate thermal kinetics and abundant oxygen defects. Further, this strong confinement is greatly beneficial for subsequent chemical transformations to obtain different Fe-based UNPs and excellent electrochemical performance. As a proof of concept, the as-prepared FeSe UNPs in IPCNs show superior lithium storage performance with an ultrahigh and stable capacity of 815.1 mAh g-1 at 0.1 A g -1 and 379.7 mAh g-1 at 5 A g-1 for 1000 cycles.

A facile synthesis of PEGylated Cu2O@SiO2/MnO2 nanocomposite as efficient photo-Fenton-like catalysts for methylene blue treatment.

The removal of toxic organic dyes from wastewater has received much attention from the perspective of environmental protection. Metal oxides see wide use in pollutant degradation due to their chemical stability, low cost, and broader light absorption spectrum. In this work, a Cu2O-centered nanocomposite Cu2O@SiO2/MnO2-PEG with an average diameter of 52 nm was prepared for the first time via a wet chemical route. In addition, highly dispersed MnO2 particles and PEG modification were realized simultaneously in one step, meanwhile, Cu2O was successfully protected under a dense SiO2 shell against oxidation. The obtained Cu2O@SiO2/MnO2-PEG showed excellent and stable photo-Fenton-like catalytic activity, attributed to integration of visible light-responsive Cu2O and H2O2-responsive MnO2. A degradation rate of 92.5% and a rate constant of 0.086 min-1 were obtained for methylene blue (MB) degradation in the presence of H2O2 under visible light for 30 min. Additionally, large amounts of •OH and 1O2 species played active roles in MB degradation. Considering the enhanced degradation of MB, this stable composite provides an efficient catalytic system for the selective removal of organic contaminants in wastewater.

A synergistic chemodynamic-photodynamic-photothermal therapy platform based on biodegradable Ce-doped MoOx nanoparticles.

Near-infrared light-induced catalysts are considered to be potential nanoagents for tumor therapy. Cerium (Ce) is a non-biotoxic lanthanide element and exhibits variable valence states for catalytic reactions. In this work, we report a one-step hydrothermal synthesis for Ce-doped MoOx (CMO) nanomaterials. The obtained CMO nanomaterials show high absorption in the NIR II regime and a high photothermal conversion efficiency of 67.7% (1064 nm). Moreover, due to the doping of Ce element, the consumption of hydrogen peroxide (H2O2) and glutathione (GSH) is boosted which enhances the chemodynamic and photodynamic therapy simultaneously. Under NIR II laser irradiation, the designed CMO nanocatalysts induce metabolism disruption and mitochondrial damage in the tumor cells. As-prepared CMO nanomaterials also show good biocompatibility and pH-responsive degradation behavior, which can be degraded rapidly under alkaline conditions (pH = 7.4) and remain stable in acidic solution (pH = 5.6). These properties make CMO nanomaterials ideal biodegradable nanotheranostic agents for synergistic chemodynamic-photodynamic-photothermal antitumor therapy.

Biodistribution, degradability and clearance of 2D materials for their biomedical applications.

Two-dimensional (2D) materials have evolved to be a class of rapidly advancing chemical entities in the biomedical field. Nevertheless, potential side effects and safety concerns severely limit their clinical translation. After administration, 2D materials cross multiple biological barriers and are distributed throughout the body. Only the portion that accumulates at the diseased sites exerts a therapeutic effect, whereas those distributed elsewhere may cause damage to healthy tissues and interference to normal physiological function of various organs. To achieve maximum therapeutic efficacy and minimum adverse effects simultaneously, the delivery of 2D materials must be targeted at diseased sites to reach therapeutic concentrations, and the materials must possess sufficient degradation and clearance rates to avoid long-term toxicity. Therefore, it is essential to understand the biodistribution and destiny of 2D materials in vivo. In this review, first, we provide a comprehensive picture of the strategies that are currently adopted for regulating the in vivo fate of 2D materials, including modulations of their size, surface properties, composition, and external stimuli. Second, we systematically review the biodistribution, degradation, and metabolism of several newly emerged 2D materials. Finally, we also discuss the development opportunities of 2D materials in the biomedical field and the challenges to be addressed.

Boosting Charge Transfer Via Heterostructure Engineering of Ti2 CTx /Na2 Ti3 O7 Nanobelts Array for Superior Sodium Storage Performance.

The poor conductivity, inert charge transmission efficiency, and irreversible Na+ trapping of Na2 Ti3 O7 result in retardant electrons/ions transportation and deficient sodium-ion storage efficiency, leading to sluggish reaction kinetics. To address these issues, an urchin-like Ti2 CTx /Na2 Ti3 O7 (Ti2 C/NTO) heterostructure sphere consisting of Ti2 C/NTO heterostructure nanobelts array is developed via a facile one-step in situ hydrothermal strategy. The Ti2 C/NTO heterostructure can obviously decrease Na+ diffusion barriers and increase electronic conductivity to improve reaction kinetics due to the built-in electric field effect and high-quantity interface region. In addition, the urchin-like vertically aligned nanobelts can reduce the diffusion distance of electrons and ions, provide favored electrolyte infiltration, adapt large volume expansion, and mitigate the aggregation to maintain structural stability during cycles, further enhancing the reaction kinetics. Furthermore, the Ti2 C/NTO heterostructure can effectively suppress many unwanted side reactions between reactive surface sites of NTO and electrolyte as well as irreversible trapping of Na+ . As a result, systematic electrochemical investigations demonstrate that the Ti2 C/NTO heterostructure as an anode material for record sodium-ion storage delivers the highest reversible capacity, the best cycling stability with 0.0065% decay rate for 4500 cycles at 2.0 A g-1 , and excellent rate capability of 172.1 mAh g-1 at 10.0 A g-1 .

Ultrasmall AgBiSe2 nanodots for CT/thermal imaging-guided photothermal tumor therapy in the NIR-II biowindow.

Stimulus-responsive ternary chalcogenide nanomaterials are regarded as promising 'all-in-one' nanotheranostics agents on account of their tunable band structures and multi-metal intrinsic properties. Herein, ultrasmall AgBiSe2 nanodots are prepared by a simple thermal injection method. It shows a narrow band gap of 0.91 eV and high absorption coefficient in the NIR-II biowindow, resulting in excellent photothermal performance. Under the irradiation of a 1064 nm laser, AgBiSe2 can induce the overexpression of intracellular heat shock protein (Hsp70) and cell apoptosis to inhibit the growth of tumor cells. The strong signal from CT/thermal imaging also provides guidance for tumor diagnosis. Importantly, AgBiSe2 can be rapidly excreted from the body, thus avoiding long term toxicity. This study presents the first biomedical application of AgBiSe2 nanodots in cancer treatment and extends the development of ternary chalcogenide-based semiconductor nanomedicine.

Research Note: The gut microbiota varies with dietary fiber levels in broilers.

It is generally accepted the gut microbiota have a profound effect on the nutrition, health, and production in poultry. To deeply understand the gut microbiota composition with the dietary fiber level in broilers, we evaluated the cecal microbiota profiles feeding on different dietary fiber level with alfalfa as additive in Dahen broilers based on 16S rRNA gene sequencing and gas chromatography. As a result, the gut microbiota diversity was greatly accelerated with the dietary fiber level. The dietary fiber stimulated the growth of many intestinal communities such as Rikenellaceae RC9 gut group, Faecalibacterium, Prevotellaceae UCG 001 and Ruminococcaceae UCG 014, and led to an altered microbial function such as Carbohydrate metabolism and Genetic information processing. Meanwhile, we found the genera Anaerofilum and Dielma were significantly correlated with the production of short chain fatty acids (SCFAs). All these results provide a reference for the broilers gut microbiota changes with different dietary fiber level. The key role of the altered microbiota with the dietary fiber may mediate beneficial effects in broiler production, which also reflect the substantial potential of dietary fiber level in poultry.

Engineering DNA quadruplexes in DNA nanostructures for biosensor construction.

DNA quadruplexes are nucleic acid conformations comprised of four strands. They are prevalent in human genomes and increasing efforts are being directed toward their engineering. Taking advantage of the programmability of Watson-Crick base-pairing and conjugation methodology of DNA with other molecules, DNA nanostructures of increasing complexity and diversified geometries have been artificially constructed since 1980s. In this review, we investigate the interweaving of natural DNA quadruplexes and artificial DNA nanostructures in the development of the ever-prosperous field of biosensing, highlighting their specific roles in the construction of biosensor, including recognition probe, signal probe, signal amplifier and support platform. Their implementation in various sensing scenes was surveyed. And finally, general conclusion and future perspective are discussed for further developments.

Intracellular Mutual Amplification of Oxidative Stress and Inhibition Multidrug Resistance for Enhanced Sonodynamic/Chemodynamic/Chemo Therapy.

Emerging noninvasive treatments, such as sonodynamic therapy (SDT) and chemodynamic therapy (CDT), have developed as promising alternatives or supplements to traditional chemotherapy. However, their therapeutic effects are limited by the hypoxic environment of tumors. Here, a biodegradable nanocomposite-mesoporous zeolitic-imidazolate-framework@MnO2 /doxorubicin hydrochloride (mZMD) is developed, which achieves enhanced SDT/CDT/chemotherapy through promoting oxidative stress and overcoming the multidrug resistance. The mZMD decomposes under both ultrasound (US) irradiation and specific reactions in the tumor microenvironment (TME). The mZM composite structure reduces the recombination rate of e- and h+ to improve SDT. MnO2 not only oxidizes glutathione in tumor cells to enhance oxidative stress, but also converts the endogenic H2 O2 into O2 to improve the hypoxic TME, which enhances the effects of chemotherapy/SDT. Meanwhile, the generated Mn2+ catalyzes the endogenic H2 O2 into ·OH for CDT, and acts as magnetic resonance imaging agent to guide therapy. In addition, dissociated Zn2+ further breaks the redox balance of TME, and co-inhibits the expression of P-glycoprotein (P-gp) with generated ROS to overcome drug resistance. Thus, the as-prepared intelligent biodegradable mZMD provides an innovative strategy to enhance SDT/CDT/chemotherapy.

Tumor microenvironment responsive self-cascade catalysis for synergistic chemo/chemodynamic therapy by multifunctional biomimetic nanozymes.

Chemodynamic therapy (CDT) is an emerging approach to treat cancer based on the tumor microenvironment (TME), but its limited content of endogenous hydrogen peroxide (H2O2) weakens the anticancer effects. Herein, a multifunctional biomimetic nanozyme (Se@SiO2-Mn@Au/DOX, named as SSMA/DOX) is fabricated, which undergoes TME responsive self-cascade catalysis to facilitate MRI guided enhanced chemo/chemodynamic therapy. The SSMA/DOX nanocomposites (NCs) responsively degrade in acidic conditions of tumor to release Se, DOX, Au and Mn2+. Mn2+ not only enables MRI to guided therapy, but also catalyzes the endogenous H2O2 into hydroxyl radical (˙OH) for CDT. In addition, the Au NPs continuously catalyze glucose to generate H2O2, enhancing CDT by supplementing a sufficiently reactive material and cutting off the energy supply of the tumor by consuming glucose. Simultaneously, Se enhances the chemotherapy of doxorubicin hydrochloride (DOX) and CDT by upregulating ROS in the tumor cells, achieving remarkable inhibition effect towards tumor. Moreover, SSMA/DOX NCs have good biocompatibility and degradability, which avoid long-term toxicity and side effects. Overall, the degradable SSMA/DOX NCs provide an innovative strategy for tumor microenvironment responsive self-cascade catalysis to enhance tumor therapy.

Gut Microbiota Signature of Obese Adults Across Different Classifications.

Purpose: Obesity is currently a major global public health issue. It has been shown by many that gut microbiota and microbial factors regulate the pathogenesis of obesity and metabolic abnormalities, but little is known about their roles in the different degrees of obesity. Here, we sought to investigate the microbial signatures of obesity of various severities. Patients and Methods: We did this by characterizing the intestinal microbiome signature in a Chinese cohort of obese patients and healthy controls using 16S rRNA gene sequencing. To this end, obesity was sub-divided into four subgroups, including "Overweight", Class I, Class II, and Class III obesity, based on body mass index (BMI). Results: Microbial diversity decreased in obese subjects, and the reduction trend was correlated with the severity of obesity. We detected an expansion of Escherichia shigella in obese patients compared to healthy controls. The family Eubacterium coprostanoligenes and Tannerellaceae, the genera Eubacterium coprostanoligenes, Lachnospiraceae NK4A136, Parabacteroides, and Akkermansia, and the species Prevotella copri were microbial biomarkers of healthy people. Gammaproteobacteria and Enterobacterales were biomarkers of being "Overweight". Erysipelatoclostridiaceae was a biomarker of Class I obesity. The class Bacilli and the order Lactobacillales were both biomarkers of Class II obesity. Negativicutes was a biomarker of Class III obesity. We further established relationships between this microbiome data and other biochemical data, including albumin, low-density lipoprotein (LDL), high-density lipoprotein (HDL), vitamin folic acid (FA) and vitamin B12 (VB12), and Interleukin-6 (IL-6) levels. Function prediction results showed a marked energy metabolism dysbiosis in obesity, especially in patients with Class III obesity. Conclusion: These results suggested that people with different levels of obesity had distinct gut microbial signatures. Decreased microbial diversity, depletion of some specific taxa, and deviation in potential functions mirrored the severity of obesity in this cohort.