GluA1 Degradation by Autophagy Contributes to Circadian Rhythm Effects on Cerebral Ischemia Injury.

The mechanisms of many diseases, including central nervous system disorders, are regulated by circadian rhythms. The development of brain disorders such as depression, autism, and stroke is strongly associated with circadian cycles. Previous studies have shown that cerebral infarct volume is smaller at night (active phase) than during the day (inactive phase) in ischemic stroke rodent models. However, the underlying mechanisms remain unclear. Increasing evidence suggests that glutamate systems and autophagy play important roles in the pathogenesis of stroke. Here, we report that GluA1 expression was decreased and autophagic activity was increased in active-phase male mouse models of stroke compared with the inactive-phase models. In the active-phase model, induction of autophagy decreased the infarct volume, whereas inhibition of autophagy increased the infarct volume. Meanwhile, GluA1 expression was decreased following activation of autophagy and increased following inhibition of autophagy. We used Tat-GluA1 to uncouple p62, an autophagic adapter, from GluA1 and found that this blocked the degradation of GluA1, an effect similar to that of inhibition of autophagy in the active-phase model. We also demonstrated that knock-out of the circadian rhythm gene Per1 abolished the circadian rhythmicity of the volume of infarction and also abolished GluA1 expression and autophagic activity in wild-type (WT) mice. Our results suggest an underlying mechanism by which the circadian rhythm participates in the autophagy-dependent regulation of GluA1 expression, which influences the volume of infarction in stroke.SIGNIFICANCE STATEMENT Circadian rhythms affect the pathophysiological mechanisms of disease. Previous studies suggested that circadian rhythms affect the infarct volume in stroke, but the underlying mechanisms remain largely unknown. Here, we demonstrate that the smaller infarct volume after middle cerebral artery occlusion/reperfusion (MCAO/R) during the active phase is related to lower GluA1 expression and activation of autophagy. The decrease in GluA1 expression during the active phase is mediated by the p62-GluA1 interaction, followed by direct autophagic degradation. In short, GluA1 is the substrate of autophagic degradation, which mainly occurs after MCAO/R during the active phase but not the inactive phase.

Organic-Inorganic Rare-Earth Double Perovskite Ferroelectric with Large Piezoelectric Response and Ferroelasticity for Flexible Composite Energy Harvesters.

Hybrid organic-inorganic perovskite (HOIP) ferroelectric materials have great potential for developing self-powered electronic transducers owing to their impressive piezoelectric performance, structural tunability and low processing temperatures. Nevertheless, their inherent brittle and low elastic moduli limit their application in electromechanical conversion. Integration of HOIP ferroelectrics and soft polymers is a promising solution. In this work, a hybrid organic-inorganic rare-earth double perovskite ferroelectric, [RM3HQ]2RbPr(NO3)6 (RM3HQ = (R)-N-methyl-3-hydroxylquinuclidinium) is presented, which possesses multiaxial nature, ferroelasticity and satisfactory piezoelectric properties, including piezoelectric charge coefficient (d33) of 102.3 pC N-1 and piezoelectric voltage coefficient (g33) of 680 × 10-3 V m N-1. The piezoelectric generators (PEG) based on composite films of [RM3HQ]2RbPr(NO3)6@polyurethane (PU) can generate an open-circuit voltage (Voc) of 30 V and short-circuit current (Isc) of 18 µA, representing one of the state-of-the-art PEGs to date. This work has promoted the exploration of new HOIP ferroelectrics and their development of applications in electromechanical conversion devices.

Stereo-Active Lone Pairs Induced Second Harmonic Generation Responses and Electrocatalytic Activity in Hybrid Material.

The lone pair electrons in the electronic structure of molecules have been a prominent research focus in chemistry for more than a century. Stable s2lone pair electrons significantly influence material properties, including thermoelectric properties, nonlinear optical properties, ferroelectricity, and electro(photo)catalysis.While major advances have been achieved in understanding the influence of lone pair electrons on material characteristics, research on this effect in organic-inorganic hybrid materials is in its initial stage. In this work, we successfully obtained a novel organic-inorganic hybrid material incorporating Ge with 4s2 lone pair electrons, (MeHDabco)2[GeBr3]4-H2O (MeHDabco = N-methyl-1,4-diazabicyclo[2.2.2]octane) (1). Driven by the stereochemically active lone pair electrons on the Ge2+, 1 crystallizes in the noncentrosymmetric space group P21 at room temperature and exhibits good second harmonic generation (SHG) responses. Interestingly, 1 also shows electrocatalytic activity for the hydrogen evolution reaction due to the existence of lone pair electrons on Ge2+ cations. The electrochemical experiment combined with the DFT calculations revealed the lone pair electrons act as both an active site for proton adsorption and facilitate the ionization of water. This work not only emphasizes the important role of lone pair electrons in material properties and functions but also provides new insight for designing novel Ge-based hybrid materials.

Molecularly Imprinted Nanomedicine for Anti-angiogenic Cancer Therapy via Blocking Vascular Endothelial Growth Factor Signaling.

The VEGF-VEGFR2 (VEGF = vascular endothelial growth factor) signaling has been a promising target in cancer therapy. However, because conventional anti-angiogenic therapeutics suffer from drawbacks, particularly severe side effects, novel anti-angiogenic strategies are much needed. Herein, we report the rational engineering of VEGF-targeted molecularly imprinted polymer nanoparticles (nanoMIP) for anti-angiogenic cancer therapy. The anti-VEGF nanomedicine was prepared via a state-of-the-art molecular imprinting approach using the N-terminal epitope of VEGF as the template. The nanoMIP could target the two major pro-angiogenic isoforms (VEGF165 and VEGF121) with high affinity and thereby effectively block the VEGF-VEGFR2 signaling, yielding a potent anti-angiogenic effect of "killing two birds with one stone". In vivo experiments demonstrated that the anti-VEGF nanoMIP effectively suppressed tumor growth via anti-angiogenesis in a xenograft model of human colon carcinoma without apparent side effects. Thus, this study not only proposes an unprecedented anti-angiogenic strategy for cancer therapy but also provides a new paradigm for the rational development of MIPs-based "drug-free" nanomedicines.

Introducing Ferroelasticity into 1D Hybrid Lead Halide Semiconductor by Halogen Substitution Strategy.

Organic-inorganic hybrid lead halide perovskites (OLHPs), represented by (CH3 NH3 )PbI3 , are one of the research focus due to their exceptional performance in optoelectronic applications, and ferroelastic domain walls are benign to their charge carrier transport that is confirmed recently. Among them, the 1D OLHPs feature better stability against desorption and moisture, but related 1D ones possessing ferroelasticity are rarely investigated and reported so far. In this work, the 1D ferroelastic semiconductor (N-iodomethyl-N-methyl-morpholinium)PbI3 ((IDMML)PbI3 ) is prepared successfully by introducing successively halogenate atoms from Cl, Br to I into the organic cation of the prototype (N,N-dimethylmorpholinium)PbI3 ((DMML)PbI3 ). Notably, (IDMML)PbI3 shows the narrow bandgap energy (≈2.34 eV) according to the ultraviolet-visible absorption spectrum and the theoretical calculation, and possesses the evident photoconductive characteristic with the on/off ratio of current of ≈50 under the 405 nm light irradiation. This work provides a new case for the ferroelastic OLHPs and will inspire intriguing research in the field of optoelectronic.

Impact of cirrhosis-related complications on posttransplant survival in patients with acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome defined as acute decompensation in patients with chronic liver disease. Liver transplantation (LT) is the most effective treatment. We aimed to assess the impact of cirrhosis-related complications pre-LT on the posttransplant prognosis of patients with ACLF. METHODS: This was an observational cohort study conducted between January 2018 and December 2020. Clinical characteristics, cirrhosis-related complications at LT and patient survival post-LT were collected. All liver recipients with ACLF were followed for 1 year post-LT. RESULTS: A total of 212 LT recipients with ACLF were enrolled, including 75 (35.4%) patients with ACLF-1, 64 (30.2%) with ACLF-2, and 73 (34.4%) with ACLF-3. The median waiting time for LT was 11 (4-24) days. The most prevalent cirrhosis-related complication was ascites (78.8%), followed by hepatic encephalopathy (57.1%), bacterial infections (48.1%), hepatorenal syndrome (22.2%) and gastrointestinal bleeding (11.3%). Survival analyses showed that patients with complications at LT had a significantly lower survival probability at both 3 months and 1 year after LT than those without complications (all P < 0.05). A simplified model was developed by assigning one point to each complication: transplantation for ACLF with cirrhosis-related complication (TACC) model. Risk stratification of TACC model identified 3 strata (≥ 4, = 3, and ≤ 2) with high, median and low risk of death after LT (P < 0.001). Moreover, the TACC model showed a comparable ability for predicting the outcome post-LT to the other four prognostic models (chronic liver failure-consortium ACLF score, Chinese Group on the Study of Severe Hepatitis B-ACLF score, model for end-stage liver disease score and Child-Turcotte-Pugh score). CONCLUSIONS: The presence of cirrhosis-related complications pre-LT increases the risk of death post-LT in patients with ACLF. The TACC model based on the number of cirrhosis-related complications pre-LT could stratify posttransplant survival, which might help to determine transplant timing for ACLF.

Molecularly Imprinted Nanobeacons Redirect Innate Immune Killing towards Triple Negative Breast Cancer.

Harnessing innate immunity is an appealing strategy for cancer treatment. Herein, we report a new strategy called molecularly imprinted nanobeacons (MINBs) for redirecting innate immune killing towards triple-negative breast cancer (TNBC). The MINBs were molecularly imprinted nanoparticles with the N-epitope of glycoprotein nonmetastatic B (GPNMB) as the template and grafted with plentiful fluorescein moieties as the hapten. The MINBs could tag the TNBC cells via binding with GPNMB and thereby provide navigation for recruiting hapten-specific antibodies. The gathered antibodies could further trigger effective Fc-domain-mediated immune killing towards the tagged cancer cells. In vivo experiments showed that the TNBC growth was significantly inhibited after MINBs treatment by intravenous injection as compared with control groups. This study not only opens a new access for redirecting innate immunity towards TNBC but also paves the way for innate immunity-based therapy of other diseases.

Probing Queuosine Modifications of Transfer RNA in Single Living Cells via Plasmonic Affinity Sandwich Assay.

Queuosine (Q) modification on tRNA plays an essential role in protein synthesis, participating in many tRNA functions such as folding, stability, and decoding. Appropriate analytical tools for the measurement of tRNA Q modifications are essential for the exploration of new roles of Q-modified tRNAs and the rationalization of their exact mechanisms. However, conventional methods for Q modification analysis suffer from apparent disadvantages, such as destructive cells, tedious procedure, and low sensitivity, which much hamper in-depth studies of Q modification-related biological questions. In this study, we developed a new approach called plasmonic affinity sandwich assay that allows for facile and sensitive determination of Q-modified tRNAs in single living cells. This method relies on the combination of plasmon-enhanced Raman scattering detection, base-paring affinity in-cell microextraction, and a set of boronate affinity and molecularly imprinted labeling nanotags for selective recognition of individual Q modifications, including queuosine, galactosyl queuosine (Gal-Q), and mannosyl queuosine (Man-Q). The developed method exhibited high affinity extraction and high specificity recognition. It allowed for the measurement of tRNA Q modifications in not only Q-rich cultured tumor cells but also Q-deficient primary tumor cells. Usefulness of this approach for investigation of the change of the Q modification level in single cells under oxidative stress was demonstrated. Because of its significant advantages over conventional methods, this approach provides a promising analytical tool for the exploration of more roles of Q-modified tRNAs and elucidation of their mechanisms.

Photothermal Therapy of Neuroblastoma via Polysialic Acid-Targeting Nanomissiles.

Exploring new targets and developing novel targeted therapies are urgently needed for neuroblastoma therapy. Polysialic acid (polySia), a linear homopolymer of sialic acid units that correlates well with tumor progression and poor prognosis, has emerged as a potential target for neuroblastoma. However, the lack of polySia-specific binding reagents has severely limited the development of polySia-targeting therapeutics for neuroblastoma. Herein, the construction of polySia-targeting nanomissiles via molecular imprinting for the photothermal therapy of neuroblastoma is reported. Oligosialic acid (oligoSia) containing 3-4 units is considered as a characteristic structure for the recognition of polySia, while oligoSia containing 4-7 units digested from polySia is employed as the template. Via boronate-affinity controllable oriented surface imprinting, oligoSia-imprinted nanoparticles (oSia-MIP) are prepared. The oSia-MIP allows for specifically recognizing polySia and targeting polySia overexpressed neuroblastoma cells in vitro and in vivo. oSia-MIP loaded with indocyanine green is prepared and experimentally demonstrated to be a potent targeted photothermal therapeutic for neuroblastoma. Equipping the core substrate with functional entities, the developed polySia targeting nanoplatform can be accommodated to various therapeutic modalities, holding great promise for neuroblastoma targeted therapy.

Two-Step Dielectric Responsive Organic-Inorganic Hybrid Material with Mid-Band Light Emission.

Hybrid organic-inorganic perovskite (HOIP) have received tremendous scientific attention because of the phase transition and photovoltaic properties. However, achieving the special perovskite structure with both two-step dielectric response and luminescence characteristics is rarely reported. Herein, we report an organic-inorganic hybrid perovskite, [(BA)2 ⋅ PbI4 ] (Compound 1, BA=n-butylamine) by introducing flexible organic cations (HBA+ ), with direct mid-band gap as 2.28 eV. Interestingly, this material exhibits two-step reversible dielectric response at 350 K and 460 K (in heating process), respectively. Besides, the photoluminescence was found: it emits charming green light under 365 nm lamp (Photoluminescence quantum yield is 9.52 %). The outstanding two-step dielectric response and luminescence characteristics of this compound might pave the way for the application of dielectric and ferroelectric functional materials in temperature sensors and mechanical switches.

Ferroelasticity in Organic-Inorganic Hybrid Perovskites.

Molecular ferroelastics have received particular attention for potential applications in mechanical switches, shape memory, energy conversion, information processing, and solar cells, by taking advantages of their low-cost, light-weight, easy preparation, and mechanical flexibility. The unique structures of organic-inorganic hybrid perovskites have been considered to be a design platform for symmetry-breaking-associated order-disorder in lattice, thereby possessing great potential for ferroelastic phase transition. Herein, we review the research progress of organic-inorganic hybrid perovskite ferroelastics in recent years, focusing on the crystal structures, dimensions, phase transitions and ferroelastic properties. In view of the few reports on molecular-based hybrid ferroelastics, we look forward to the structural design strategies of molecular ferroelastic materials, as well as the opportunities and challenges faced by molecular-based hybrid ferroelastic materials in the future. This review will have positive guiding significance for the synthesis and future exploration of organic-inorganic hybrid molecular ferroelastics.

Integrated Reversible Thermochromism, High Tc , Dielectric Switch and Narrow Band Gap in One Multifunctional Ferroic.

Organic-inorganic Hybrid (OIH) materials for multifunctional switchable applications have attracted enormous attention in recent years due to their excellent optoelectronic properties and good structural tunability. However, it still remains challenging to fabricate one simple OIH compound with multi-functionals properties, such as dielectric switching, thermochromic properties, semiconductor characteristics and ferroelasticity. Under this context, we successfully synthesized [2-(2-fluorophenyl)ethan-1- ammonium]2 SnBr6 (compound 1), which has a higher phase transition temperature of 427.7 K. Additionally, it exhibits a semiconducting property with an indirect band gap of 2.36 eV. Combining ferroelastic, narrow band gap, thermochromic, and dielectric properties, compound 1 can be considered as a rarely reported multi-functional ferroelastic material, which is expected to give inspiration for broadening the applications in the smart devices field.

Transition-Metal-Free Cascade Approach for the Synthesis of Functionalized Biaryls by SNAr of Arylhydroxylamines with Arylsulfonium Salts.

We report a transition-metal-free protocol for the synthesis of functionalized biaryls through nucleophilic aromatic substitution (SNAr) of arylhydroxylamines to arylsulfonium salts. With this protocol, structurally diverse functionalized biaryls were obtained smoothly in moderate to good yields. Merits of this transformation include mild reaction conditions, broad substrate scope, great functional group tolerance, feasibility of a one-pot procedure, and ease of handing and scale-up.

Alterations in the human oral and gut microbiomes and lipidomics in COVID-19.

OBJECTIVE: To characterise the oral microbiome, gut microbiome and serum lipid profiles in patients with active COVID-19 and recovered patients; evaluate the potential of the microbiome as a non-invasive biomarker for COVID-19; and explore correlations between the microbiome and lipid profile. DESIGN: We collected and sequenced 392 tongue-coating samples, 172 faecal samples and 155 serum samples from Central China and East China. We characterised microbiome and lipid molecules, constructed microbial classifiers in discovery cohort and verified their diagnostic potential in 74 confirmed patients (CPs) from East China and 37 suspected patients (SPs) with IgG positivity. RESULTS: Oral and faecal microbial diversity was significantly decreased in CPs versus healthy controls (HCs). Compared with HCs, butyric acid-producing bacteria were decreased and lipopolysaccharide-producing bacteria were increased in CPs in oral cavity. The classifiers based on 8 optimal oral microbial markers (7 faecal microbial markers) achieved good diagnostic efficiency in different cohorts. Importantly, diagnostic efficacy reached 87.24% in the cross-regional cohort. Moreover, the classifiers successfully diagnosed SPs with IgG antibody positivity as CPs, and diagnostic efficacy reached 92.11% (98.01% of faecal microbiome). Compared with CPs, 47 lipid molecules, including sphingomyelin (SM)(d40:4), SM(d38:5) and monoglyceride(33:5), were depleted, and 122 lipid molecules, including phosphatidylcholine(36:4p), phosphatidylethanolamine (PE)(16:0p/20:5) and diglyceride(20:1/18:2), were enriched in confirmed patients recovery. CONCLUSION: This study is the first to characterise the oral microbiome in COVID-19, and oral microbiomes and lipid alterations in recovered patients, to explore their correlations and to report the successful establishment and validation of a diagnostic model for COVID-19.

Thermographic follow-up of postherpetic neuralgia (PHN) subsequent to Ramsay Hunt syndrome with multicranial nerve (V, VII, VIII and IX) involvement: a case report.

BACKGROUND: Ramsay Hunt syndrome (RHS) is caused by a reactivation of varicella-zoster virus (VZV) infection, and it is characterized by the symptoms of facial paralysis, otalgia, auricular rash, and/or an oral lesion. Elderly patients or immunocompromised patients, deep pain at the initial visit and no prompt treatment are significant predictors of postherpetic neuralgia (PHN). When PHN occurs, especially involved cranial polyneuropathy, multiple modalities should be administered for patients with the intractable PHN. The use of thermography in the follow-up of PHN secondary to RHS with multicranial nerve involvement has not yet been described yet in the literature. CASE PRESENTATION: The patient was a 78-year-old man with the chief complaint of a 3-month history of PHN secondary to RHS with polycranial nerve (V, VII, VIII, and IX) involvement. Multimodality therapy with oral gabapentin, pulsed radiofrequency (PRF) application to the Gasserian ganglion for pain in the trigeminal nerve region, linear-polarized near-infrared light irradiation for pain in the facial nerve region, and 2% lidocaine spray for pain in the glossopharyngeal nerve region was used to the treat patient, and follow-up evaluations included thermography. This comprehensive treatment obviously improved the quality of life, resulting in considerable pain relief, as indicated by a decrease in the numerical rating scale (NRS) score from 9 to 3 and a decrease in thermal imaging temperature from higher to average temperature on the ipsilateral side compared with the contralateral side. Lidocaine spray on the tonsillar branches of the glossopharyngeal nerve resulted in an improvement in odynophagia, and the NRS score decreased from 9 to 0 for glossopharyngeal neuralgia after three applications. CONCLUSION: Although the use of thermography in the follow-up of RHS with multiple cranial nerve (V, VII, VIII, and IX) involvement is very rare, in this patient, thermal imaging showed the efficacy of combination therapy (oral gabapentin, 2% lidocaine sprayed, PRF application and linear-polarized near-infrared light irradiation) and that is a good option for treatment.

Synthesis of non-C2 symmetrical NOBIN-type biaryls through a cascade N-arylation and [3,3]-sigmatropic rearrangement from O-arylhydroxylamines and diaryliodonium salts.

We developed herein a regioselective construction of non-C2 symmetrical NOBIN-type biaryls through a cascade N-arylation and [3,3]-sigmatropic rearrangement from O-arylhydroxylamines and diaryliodonium salts under mild conditions. The employment of copper salt could inhibit the further O-arylation of the newly formed biaryl products, otherwise, O-arylated NOBIN-type products were furnished in moderate to good isolated yields. The products of this protocol can be further converted into highly valuable functional molecules and heterocycles.

Noncentrosymmetric Weyl phase and topological phase transition in bulk MoTe.

Ideal topological materials are those stable materials with less nontrivial band crossing near the Fermi surface and a long Fermi arc. By means of first-principles calculations, here we present that the 3D monochalcogenide molybdenum telluride (Pm-MoTe) without an inversion center shows a type-II Weyl semimetal (WSM) phase which cannot checked by symmetry index method. A total of eight Weyl points (WPs) are found in different quadrants of the Brillouin zone (BZ) of Pm-MoTe, which guarantee a long Fermi arc. The WSM phase is robust against the spin-orbit coupling (SOC) effect because of mirror symmetry and time reversal symmetry. It is also found that a topological phase transition can be tuned by strain. For different types of strain, the number of WPs can be effectively modulated to a minimum number, and their energies could be closer to Fermi level. These findings propose a promising material candidate that partly satisfies the ideal WSM criteria and extends the potential applications of the tunable topological phase.

Microbiome-miRNA interactions in the progress from undifferentiated arthritis to rheumatoid arthritis: evidence, hypotheses, and opportunities.

The human microbiome has attracted attention for its potential utility in precision medicine. Increasingly, more researchers are recognizing changes in intestinal microbiome can upset the balance between pro- and anti-inflammatory factors of host immune system, potentially contributing to arthritis immunopathogenesis. Patients who develop rheumatoid arthritis from undifferentiated arthritis can face multiple irreversible joint lesions and even deformities. Strategies for identifying undifferentiated arthritis patients who have a tendency to develop rheumatoid arthritis and interventions to prevent rheumatoid arthritis development are urgently needed. Intestinal microbiome dysbiosis and shifts in the miRNA profile affect undifferentiated arthritis progression, and may play an important role in rheumatoid arthritis pathophysiologic process via stimulating inflammatory cytokines and disturbing host and microbial metabolic functions. However, a causal relationship between microbiome-miRNA interactions and rheumatoid arthritis development from undifferentiated arthritis has not been uncovered yet. Changes in the intestinal microbiome and miRNA profiles of undifferentiated arthritis patients with different disease outcomes should be studied together to uncover the role of the intestinal microbiome in rheumatoid arthritis development and to identify potential prognostic indicators of rheumatoid arthritis in undifferentiated arthritis patients. Herein, we discuss the possibility of microbiome-miRNA interactions contributing to rheumatoid arthritis development and describe the gaps in knowledge regarding their influence on undifferentiated arthritis prognosis that should be addressed by future studies.

Purple non-sulfur bacteria technology: a promising and potential approach for wastewater treatment and bioresources recovery.

Shortage of water, energy, and bioresources in the world has led to the exploration of new technologies that achieve resource recovery from wastewater, which has become a new sustainable trend. Photosynthetic non-sulfur bacteria (PNSB), the most ancient photo microorganism, not only treats different wastewater types, but also generates PNSB cells, which are non-toxic bioresources and containing many value-added products. These bioresources can be used as raw materials in the agricultural, food, and medical industries. Therefore, PNSB or PNSB-based wastewater resource recovery technology can be simultaneously used to treat wastewater and produce useful bioresources. Compared with traditional wastewater treatment, this technology can reduce CO2 emissions, promote the N recovery ratio and prevent residual sludge disposal or generation. After being developed for over half a century, PNSB wastewater resource recovery technology is currently extended towards industrial applications. Here, this technology is comprehensively introduced in terms of (1) PNSB characteristics and metabolism; (2) PNSB wastewater treatment and bioresource recovery efficiency; (3) the relative factors influencing the performance of this technology, including light, oxygen, strains, wastewater types, hydraulic retention time, on wastewater treatment, and resource production; (4) PNSB value-added bioresources and their generation from wastewater; (5) the scale-up history of PNSB technology; (6) Finally, the future perspectives and challenges of this technology were also analysed and summarised.

Alterations of the Gut Microbiota in Patients With Coronavirus Disease 2019 or H1N1 Influenza.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging serious global health problem. Gastrointestinal symptoms are common in COVID-19 patients, and severe acute respiratory syndrome coronavirus 2 RNA has been detected in stool specimens. However, the relationship between the gut microbiome and disease remains to be established. METHODS: We conducted a cross-sectional study of 30 patients with COVID-19, 24 patients with influenza A(H1N1), and 30 matched healthy controls (HCs) to identify differences in the gut microbiota by 16S ribosomal RNA gene V3-V4 region sequencing. RESULTS: Compared with HCs, COVID-19 patients had significantly reduced bacterial diversity; a significantly higher relative abundance of opportunistic pathogens, such as Streptococcus, Rothia, Veillonella, and Actinomyces; and a lower relative abundance of beneficial symbionts. Five biomarkers showed high accuracy for distinguishing COVID-19 patients from HCs with an area under the curve (AUC) up to 0.89. Patients with H1N1 displayed lower diversity and different overall microbial composition compared with COVID-19 patients. Seven biomarkers were selected to distinguish the 2 cohorts (AUC = 0.94). CONCLUSIONS: The gut microbial signature of patients with COVID-19 was different from that of H1N1 patients and HCs. Our study suggests the potential value of the gut microbiota as a diagnostic biomarker and therapeutic target for COVID-19, but further validation is needed.