RESUMEN
BACKGROUND: During the pandemic, a notable increase in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), conditions that warrant emergent management, was reported. We aimed to investigate the trend of DKA- and HHS-related mortality and excess deaths during the pandemic. METHODS: Annual age-standardized mortality rates related to DKA and HHS between 2006 and 2021 were estimated using a nationwide database. Forecast analyses based on prepandemic data were conducted to predict the mortality rates during the pandemic. Excess mortality rates were calculated by comparing the observed versus predicted mortality rates. Subgroup analyses of demographic factors were performed. RESULTS: There were 71 575 DKA-related deaths and 8618 HHS-related deaths documented during 2006-2021. DKA, which showed a steady increase before the pandemic, demonstrated a pronounced excess mortality during the pandemic (36.91% in 2020 and 46.58% in 2021) with an annual percentage change (APC) of 29.4% (95% CI: 16.0%-44.0%). Although HHS incurred a downward trend during 2006-2019, the excess deaths in 2020 (40.60%) and 2021 (56.64%) were profound. Pediatric decedents exhibited the highest excess mortality. More than half of the excess deaths due to DKA were coronavirus disease 2019 (COVID-19) related (51.3% in 2020 and 63.4% in 2021), whereas only less than a quarter of excess deaths due to HHS were COVID-19 related. A widened racial/ethnic disparity was observed, and females exhibited higher excess mortality than males. CONCLUSIONS: The DKA- and HHS-related excess mortality during the pandemic and relevant disparities emphasize the urgent need for targeted strategies to mitigate the escalated risk in these populations during public health crises.
Asunto(s)
COVID-19 , Cetoacidosis Diabética , Coma Hiperglucémico Hiperosmolar no Cetósico , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , COVID-19/complicaciones , Cetoacidosis Diabética/mortalidad , Cetoacidosis Diabética/epidemiología , Masculino , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Coma Hiperglucémico Hiperosmolar no Cetósico/mortalidad , Coma Hiperglucémico Hiperosmolar no Cetósico/epidemiología , Coma Hiperglucémico Hiperosmolar no Cetósico/complicaciones , Adulto , Anciano , Adolescente , Niño , Adulto Joven , SARS-CoV-2 , Pandemias , Preescolar , Lactante , Anciano de 80 o más AñosRESUMEN
With the increasing of computer power and rapid expansion of biological data, the application of bioinformatics tools has become the mainstream approach to address biological problems. The accurate identification of protein function by bioinformatics tools is crucial for both biomedical research and drug discovery, making it a hot topic of research. In this paper, we categorize bioinformatics-based protein function prediction methods into three categories: protein sequence-based methods, protein structure-based methods, and protein interaction networks-based methods. We further analyze these specific algorithms, highlighting the latest research advancements and providing valuable references for the application of bioinformatics-based protein function prediction in biomedical research and drug discovery.
Asunto(s)
Algoritmos , Biología Computacional , Proteínas , Biología Computacional/métodos , Proteínas/genética , Proteínas/metabolismo , Proteínas/química , Conformación Proteica , Mapas de Interacción de Proteínas , Análisis de Secuencia de Proteína , Secuencia de Aminoácidos , Descubrimiento de DrogasRESUMEN
Background: We aimed to determine the trend of TB-related deaths during the COVID-19 pandemic. Methods: TB-related mortality data of decedents aged ≥25 years from 2006 to 2021 were analyzed. Excess deaths were estimated by determining the difference between observed and projected mortality rates during the pandemic. Results: A total of 18,628 TB-related deaths were documented from 2006 to 2021. TB-related age-standardized mortality rates (ASMRs) were 0.51 in 2020 and 0.52 in 2021, corresponding to an excess mortality of 10.22 and 9.19%, respectively. Female patients with TB demonstrated a higher relative increase in mortality (26.33 vs. 2.17% in 2020; 21.48 vs. 3.23% in 2021) when compared to male. Female aged 45-64 years old showed a surge in mortality, with an annual percent change (APC) of -2.2% pre-pandemic to 22.8% (95% CI: -1.7 to 68.7%) during the pandemic, corresponding to excess mortalities of 62.165 and 99.16% in 2020 and 2021, respectively; these excess mortality rates were higher than those observed in the overall female population ages 45-64 years in 2020 (17.53%) and 2021 (33.79%). Conclusion: The steady decline in TB-related mortality in the United States has been reversed by COVID-19. Female with TB were disproportionately affected by the pandemic.
Asunto(s)
COVID-19 , Tuberculosis , Humanos , COVID-19/mortalidad , Femenino , Persona de Mediana Edad , Masculino , Estados Unidos/epidemiología , Adulto , Anciano , Tuberculosis/mortalidad , Factores Sexuales , Anciano de 80 o más Años , PandemiasRESUMEN
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare in the United States. AIM: To investigate COVID-19-related and non-COVID-19-related death and characteristics associated with excess death among inflammatory bowel disease (IBD) decedents. METHODS: We performed a register-based study using data from the National Vital Statistics System, which reports death data from over 99% of the United States population, from January 1, 2006 through December 31, 2021. IBD-related deaths among adults 25 years and older were stratified by age, sex, race/ethnicity, place of death, and primary cause of death. Predicted and actual age-standardized mortality rates (ASMRs) per 100000 persons were compared. RESULTS: 49782 IBD-related deaths occurred during the study period. Non-COVID-19-related deaths increased by 13.14% in 2020 and 18.12% in 2021 [2020 ASMR: 1.55 actual vs 1.37 predicted, 95% confidence interval (CI): 1.26-1.49; 2021 ASMR: 1.63 actual vs 1.38 predicted, 95%CI: 1.26-1.49]. In 2020, non-COVID-19-related mortality increased by 17.65% in ulcerative colitis (UC) patients between the ages of 25 and 65 and 36.36% in non-Hispanic black (NHB) Crohn's disease (CD) patients. During the pandemic, deaths at home or on arrival and at medical facilities as well as deaths due to neoplasms also increased. CONCLUSION: IBD patients suffered excess non-COVID-19-related death during the pandemic. Excess death was associated with younger age among UC patients, and with NHB race among CD patients. Increased death at home or on arrival and due to neoplasms suggests that delayed presentation and difficulty accessing healthcare may have led to increased IBD mortality.
Asunto(s)
COVID-19 , Causas de Muerte , Enfermedades Inflamatorias del Intestino , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estados Unidos/epidemiología , Anciano , Enfermedades Inflamatorias del Intestino/mortalidad , SARS-CoV-2 , Sistema de Registros/estadística & datos numéricos , Anciano de 80 o más Años , Pandemias , Colitis Ulcerosa/mortalidad , Colitis Ulcerosa/etnología , Enfermedad de Crohn/mortalidad , Enfermedad de Crohn/etnología , Enfermedad de Crohn/diagnóstico , Factores de EdadRESUMEN
Particles, ranging from submicron to nanometer scale, can be broadly categorized into biological and non-biological types. Submicron-to-nanoscale bioparticles include various bacteria, viruses, liposomes, and exosomes. Non-biological particles cover various inorganic, metallic, and carbon-based particles. The effective manipulation of these submicron to nanoparticles, including their separation, sorting, enrichment, assembly, trapping, and transport, is a fundamental requirement for different applications. Acoustofluidics, owing to their distinct advantages, have emerged as a potent tool for nanoparticle manipulation over the past decade. Although recent literature reviews have encapsulated the evolution of acoustofluidic technology, there is a paucity of reports specifically addressing the acoustical manipulation of submicron to nanoparticles. This article endeavors to provide a comprehensive study of this topic, delving into the principles, apparatus, and merits of acoustofluidic manipulation of submicron to nanoparticles, and discussing the state-of-the-art developments in this technology. The discourse commences with an introduction to the fundamental theory of acoustofluidic control and the forces involved in nanoparticle manipulation. Subsequently, the working mechanism of acoustofluidic manipulation of submicron to nanoparticles is dissected into two parts, dominated by the acoustic wave field and the acoustic streaming field. A critical analysis of the advantages and limitations of different acoustofluidic platforms in nanoparticles control is presented. The article concludes with a summary of the challenges acoustofluidics face in the realm of nanoparticle manipulation and analysis, and a forecast of future development prospects.
RESUMEN
Controllable photofluorochromic systems with high contrast and multicolor in both solutions and solid states are ideal candidates for the development of dynamic artificial intelligence. However, it is still challenging to realize multiple photochromism within one single molecule, not to mention good controllability. Herein, we report an aggregation-induced emission luminogen TPE-2MO2NT that undergoes oxidation cleavage upon light irradiation and is accompanied by tunable multicolor emission from orange to blue with time-dependence. The photocleavage mechanism revealed that the self-generation of reactive oxidants driving the catalyst-free oxidative cleavage process. A comprehensive analysis of TPE-2MO2NT and other comparative molecules demonstrates that the TPE-2MO2NT molecular scaffold can be easily modified and extended. Further, the multicolor microenvironmental controllability of TPE-2MO2NT photoreaction within polymer matrices enables the fabrication of dynamic fluorescence images and 4D information codes, providing strategies for advanced controllable information encryption.
RESUMEN
Light-driven carboxylation offers a promising approach for synthesizing valuable fine chemicals under mild conditions. Here we disclose a heterogeneous photocatalytic strategy of C(sp2)-H activation of formate for hydrocarboxylation of alkenes over zinc indium sulfide (ZnIn2S4) under visible light. This protocol functions well with a variety of substituted styrenes with good to excellent yields; it also works for unactivated alkenes albeit with lower yields. Mechanistic studies confirm the existence of CO2â - as a key intermediate. It was found that C(sp2)-H activation of formate is induced by Sâ species on the surface of ZnIn2S4 via hydrogen atom transfer (HAT) instead of a photogenerated hole oxidation mechanism. Moreover, both cleavage of the C(sp2)-H of HCOO- and formation of a benzylic anion were found to be involved in the rate-determining step for the hydrocarboxylation of styrene.
RESUMEN
Fluorescent imaging and biosensing in the near-infrared-II (NIR-II) window holds great promise for non-invasive, radiation-free, and rapid-response clinical diagnosis. However, it's still challenging to develop bright NIR-II fluorophores. In this study, we report a new strategy to enhance the brightness of NIR-II aggregation-induced emission (AIE) fluorophores through intramolecular electrostatic locking. By introducing sulfur atoms into the side chains of the thiophene bridge in TSEH molecule, the molecular motion of the conjugated backbone can be locked through intramolecular interactions between the sulfur and nitrogen atoms. This leads to enhanced NIR-II fluorescent emission of TSEH in both solution and aggregation states. Notably, the encapsulated nanoparticles (NPs) of TSEH show enhanced brightness, which is 2.6-fold higher than TEH NPs with alkyl side chains. The in vivo experiments reveal the feasibility of TSEH NPs in vascular and tumor imaging with a high signal-to-background ratio and precise resection for tiny tumors. In addition, polystyrene nanospheres encapsulated with TSEH are utilized for antigen detection in lateral flow assays, showing a signal-to-noise ratio 1.9-fold higher than the TEH counterpart in detecting low-concentration antigens. This work highlights the potential for developing bright NIR-II fluorophores through intramolecular electrostatic locking and their potential applications in clinical diagnosis and biomedical research.
Asunto(s)
Colorantes Fluorescentes , Rayos Infrarrojos , Imagen Óptica , Electricidad Estática , Colorantes Fluorescentes/química , Humanos , Nanopartículas/química , Tiofenos/química , Animales , Ratones , Estructura MolecularRESUMEN
Clinically, the immune checkpoint inhibitor anti-PD-1 antibody has shown a certain effect in the treatment of hepatocellular carcinoma (HCC), which is limited to a small number of patients with HCC. This study aims to reveal whether carnosic acid nanocluster-based framework (CA-NBF) has a sensitization effect on anti-PD-1 antibody in the treatment of HCC at the cellular and animal levels. MHCC97H cells were treated with CA-NBF, anti-PD-1 and their combination. The effects of CA-NBF and anti-PD-1 on cell proliferation, cell cycle, apoptosis, invasion, and migration were evaluated by MTT assay, flow cytometry, and scratch test. The effects of CA-NBF and anti-PD-1 on Wnt/ß-catenin signaling pathway in MHCC97H cells were detected. A BALB/C nude mouse model of hepatocellular carcinoma was established, and the tumor growth was observed at different time points. The expression of cytotoxic T lymphocyte and helper T lymphocyte markers CD8 and CD4 in tumor tissues was detected by immunohistochemistry. Western blotting was used to detect the Wnt/ß-catenin signaling pathway proteins (Wnt-3a, ß-catenin, and GSK-3ß) level in tumor tissues after CA-NBF and anti-PD-1 treatment. CA-NBF activity was significantly higher than CA, which could prominently reduce the proliferation, migration and invasion of MHCC97H cells and enhance apoptosis by inactivating Wnt/ß-catenin signaling pathway. CA-NBF combined with anti-PD-1 antibody further enhanced cell proliferation, migration, invasion and pro-apoptosis but had no significant effect on Wnt/ß-catenin signaling pathway. CA-NBF in vivo improved the tumor response to PD1 immune checkpoint blockade in HCC, manifested by reducing tumor size and weight, promoting CD4 and CD8 expression. CA-NBF combined with anti-PD-1 have stronger immunomodulatory and anticancer effects without increasing biological toxicity.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Humanos , Ratones Endogámicos BALB C , Inhibidores de Puntos de Control Inmunológico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Glucógeno Sintasa Quinasa 3 beta , Neoplasias Hepáticas/tratamiento farmacológico , Carcinogénesis , InmunoterapiaRESUMEN
Anammox bacteria grow slowly and can be affected by large pH fluctuations. Using suitable buffers could make the start-up of anammox reactors easy and rapid. In this study, the effects of three kinds of buffers on the nitrogen removal and growth characteristics of anammox sludge were investigated. Reactors with CO2/NaHCO3 buffer solution (CCBS) performed the best in nitrogen removal, while 4-(2-hydroxyerhyl)piperazine-1-ethanesulfonic acid (HEPES) and phosphate buffer solution (PBS) inhibited the anammox activity. Reactors with 50 mmol/L CCBS could start up in 20 days, showing the specific anammox activity and anammox activity of 1.01±0.10 gN/(gVSS·day) and 0.83±0.06 kgN/(m3·day), respectively. Candidatus Kuenenia was the dominant anammox bacteria, with a relative abundance of 71.8%. Notably, anammox reactors could also start quickly by using 50 mmol/L CCBS under non-strict anaerobic conditions. These findings are meaningful for the quick start-up of engineered anammox reactors and prompt enrichment of anammox bacteria.
Asunto(s)
Oxidación Anaeróbica del Amoníaco , Dióxido de Carbono , Reactores Biológicos/microbiología , Oxidación-Reducción , Aguas del Alcantarillado/microbiología , Bacterias , Nitrógeno , Anaerobiosis , DesnitrificaciónRESUMEN
Zeolite is considered an ideal catalyst for olefin hydration due to its high specific surface area and abundant acid sites. However, the immiscibility of the water-oil two phases in olefin hydration limits mass transfer, and the side reaction of etherification occurs acutely, resulting in a low yield of alcohol. Thus, water-oil amphiphilic HZSM-5 was prepared by sulfonating silanized zeolite. The successful introduction of organic and sulfonic acid groups is demonstrated by FT-IR, TG, and water contact angles. Amphiphilic HZSM-5 can stabilize the Pickering emulsion and catalyze cyclopentene hydration at the phase interface. In addition, NH3-TPD and Py-IR show that the amount of strong BroÌ·nsted acid sites of zeolites increases significantly after sulfonation. This facilitates the rate-determining step of cyclopentene activation by H+ to form carbocation. Moreover, the nucleophilic side reactions are inhibited by a high concentration of H+. Finally, under the optimized reaction condition, the conversion of cyclopentene can achieve 5.066% with a selectivity of 85.37% to cyclopentanol, which almost reaches the reaction equilibrium.
RESUMEN
BACKGROUND: Activated sludge (AS) systems in wastewater treatment plants (WWTPs) harbor enormous viruses that regulate microbial metabolism and nutrient cycling, significantly influencing the stability of AS systems. However, our knowledge about the diversity of viral taxonomic groups and functional traits in global AS systems is still limited. To address this gap, we investigated the global diversity and biogeography of DNA viral communities in AS systems using 85,114 viral operational taxonomic units (vOTUs) recovered from 144 AS samples collected across 54 WWTPs from 13 different countries. RESULTS: AS viral communities and their functional traits exhibited distance-decay relationship (DDR) at the global scale and latitudinal diversity gradient (LDG) from equator to mid-latitude. Furthermore, it was observed that AS viral community and functional gene structures were largely driven by the geographic factors and wastewater types, of which the geographic factors were more important. Carrying and disseminating auxiliary metabolic genes (AMGs) associated with the degradation of polysaccharides, sulfate reduction, denitrification, and organic phosphoester hydrolysis, as well as the lysis of crucial functional microbes that govern biogeochemical cycles were two major ways by which viruses could regulate AS functions. It was worth noting that our study revealed a high abundance of antibiotic resistance genes (ARGs) in viral genomes, suggesting that viruses were key reservoirs of ARGs in AS systems. CONCLUSIONS: Our results demonstrated the highly diverse taxonomic groups and functional traits of viruses in AS systems. Viral lysis of host microbes and virus-mediated HGT can regulate the biogeochemical and nutrient cycles, thus affecting the performance of AS systems. These findings provide important insights into the viral diversity, function, and ecology in AS systems on a global scale. Video Abstract.
Asunto(s)
Aguas del Alcantarillado , Virus , Aguas Residuales , Virus/genética , Ecología , Virus ADN/genética , ADNRESUMEN
Background: Globally, more than 10 million new stroke cases occur annually, of which aphasia accounts for about one-third. Aphasia has become an independent predictor of functional dependence and death for the stroke population. The closed-loop rehabilitation of combining behavioral therapy with central nerve stimulation seems to be the research trend of post-stroke aphasia (PSA) due to its advantages in improving linguistic deficits. Objective: To verify the clinical efficacy of a closed-loop rehabilitation program combining melodic intonation therapy (MIT) with transcranial direct current stimulation (tDCS) for PSA. Methods: This was a single-center, assessor-blinded, randomized controlled clinical trial, which screened 179 patients and included 39 PSA subjects, with the registration number ChiCTR2200056393 in China. Demographic and clinical data were documented. The primary outcome was the Western Aphasia Battery (WAB) used to assess language function, and the secondary outcomes included Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment (FMA), and Barthel Index (BI) for evaluating cognition, motor, and activities of daily living, respectively. With the computer-generated randomization sequence, subjects were randomly divided into the conventional group (CG), MIT combined with sham stimulation group (SG), and MIT combined with tDCS group (TG). After the three-week intervention, the functional changes in each group were analyzed by the paired sample T-test, and the functional difference between the three groups was analyzed by ANOVA. Results: There was no statistical difference on the baseline. After the intervention, the WAB's aphasia quotient (WAB-AQ), MoCA, FMA, and BI were statistically different in SG and TG, including all the sub-items in WAB and FMA, while only listening comprehension, FMA, and BI were statistically different in CG. The differences of WAB-AQ, MoCA, and FMA were statistically different among the three groups, but BI was not. The post hoc test results revealed that the changes of WAB-AQ and MoCA in TG were more significant than the others. Conclusion: MIT combined with tDCS can augment the positive effect on language and cognitive recovery in PSA.
RESUMEN
Genetic code expansion enables the site-specific incorporation of noncanonical amino acids (ncAAs) into proteins both in vitro and in vivo. In addition to a widely applied nonsense suppression strategy, the use of quadruplet codons could further expand the genetic code. A general approach to genetically incorporate ncAAs in response to quadruplet codons is achieved by utilizing an engineered aminoacyl-tRNA synthetase (aaRS) together with a tRNA variant containing an expanded anticodon loop. Here we provide a protocol to decode quadruplet UAGA codon with a ncAA in mammalian cells. We also describe microscopy imaging and flow cytometry analysis of ncAA mutagenesis in response to quadruplet codons.
Asunto(s)
Aminoacil-ARNt Sintetasas , Código Genético , Animales , Codón/genética , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Anticodón , Aminoácidos/genética , Aminoácidos/metabolismo , Aminoacil-ARNt Sintetasas/genética , Aminoacil-ARNt Sintetasas/metabolismo , Codón de Terminación , Mamíferos/genéticaRESUMEN
Protein tyrosine O-sulfation (PTS) plays a crucial role in numerous extracellular protein-protein interactions. It is involved in diverse physiological processes and the development of human diseases, including AIDS and cancer. To facilitate the study of PTS in live mammalian cells, an approach for the site-specific synthesis of tyrosine-sulfated proteins (sulfoproteins) was developed. This approach takes advantage of an evolved Escherichia coli tyrosyl-tRNA synthetase to genetically encode sulfotyrosine (sTyr) into any proteins of interest (POI) in response to a UAG stop codon. Here, we give a step-by-step account of the incorporation of sTyr in HEK293T cells using the enhanced green fluorescent protein as an example. This method can be widely applied to incorporating sTyr into any POI to investigate the biological functions of PTS in mammalian cells.
Asunto(s)
Escherichia coli , Tirosina , Animales , Humanos , Células HEK293 , Tirosina/metabolismo , Codón de Terminación , Escherichia coli/genética , Escherichia coli/metabolismo , Mamíferos/genéticaRESUMEN
BACKGROUND: US progress toward ending the HIV epidemic was disrupted during the COVID-19 pandemic. OBJECTIVES: To determine the impact of the pandemic on HIV-related mortality and potential disparities. METHODS: Using data from the Centers for Disease Control and Prevention and the United States (US) Census Bureau, HIV-related mortality data of decedents aged ≥25 years between 2012 and 2021 were analyzed. Excess HIV-related mortality rates were estimated by determining the difference between observed and projected mortality rates during the pandemic. The trends of mortality were quantified with joinpoint regression analysis. RESULTS: Of the 79,725 deaths documented in adults aged 25 years and older between 2012 and 2021, a significant downward trend was noted in HIV-related mortality rates before the pandemic, followed by a surge during the pandemic. The observed mortality rates were 18.8% (95% confidence interval [CI]: 13.1%-25.5%) and 25.4% (95%CI: 19.9%-30.4%) higher than the projected values in 2020 and 2021, respectively. Both of these percentages were higher than that in the general population in 2020 (16.4%, 95%CI: 14.9%-17.9%) and 2021 (19.8%, 95%CI: 18.0%-21.6%), respectively. Increased HIV-related mortality was observed across all age subgroups, but those aged 25-44 years demonstrated the greatest relative increase and the lowest COVID-19-related deaths when compared to middle- and old-aged decedents. Disparities were observed across racial/ethnic subgroups and geographic regions. CONCLUSIONS: The pandemic led to a reversal in the attainments made to reduce the prevalence of HIV. Individuals living with HIV were disproportionately affected during the pandemic. Thoughtful policies are needed to address the disparity in excess HIV-related mortality.
Asunto(s)
COVID-19 , Infecciones por VIH , Adulto , Humanos , Estados Unidos/epidemiología , Persona de Mediana Edad , Anciano , Pandemias , Grupos Raciales , Predicción , Infecciones por VIH/epidemiología , MortalidadRESUMEN
Functional materials with multi-responsive properties and good controllability are highly desired for developing bioinspired and intelligent multifunctional systems. Although some chromic molecules have been developed, it is still challenging to realize in situ multicolor fluorescence changes based on a single luminogen. Herein, we reported an aggregation-induced emission (AIE) luminogen called CPVCM, which can undergo a specific amination with primary amines to trigger luminescence change and photoarrangement under UV irradiation at the same active site. Detailed mechanistic insights were carried out to illustrate the reactivity and reaction pathways. Accordingly, multiple-colored images, a quick response code with dynamic colors, and an all-round information encryption system were demonstrated to show the properties of multiple controls and responses. It is believed that this work not only provides a strategy to develop multiresponsive luminogens but also develops an information encryption system based on luminescent materials.
RESUMEN
Immunocompromised status and interrupted routine care may render patients with cirrhosis vulnerable to the coronavirus disease 2019 (COVID-19) pandemic. A nationwide dataset that includes more than 99% of the decedents in the U.S. between April 2012 and September 2021 was used. Projected age-standardized mortality during the pandemic were estimated according to prepandemic mortality rates, stratified by season. Excess deaths were determined by estimating the difference between observed and projected mortality rates. A temporal trend analysis of observed mortality rates was also performed in 0.83 million decedents with cirrhosis between April 2012 and September 2021 was included. Following an increasing trend of cirrhosis-related mortality before the pandemic, with a semiannual percentage change (SAPC) of 0.54% [95% confidence interval (CI): (0.0-1.0%), p=0.036], a precipitous increase with seasonal variation occurred during the pandemic (SAPC 5.35, 95% CI: 1.9-8.9, p=0.005). Significantly increased mortality rates were observed in those with alcohol-associated liver disease (ALD), with a SAPC of 8.44 (95% CI: 4.3-12.8, p=0.001) during the pandemic. All-cause mortality of nonalcoholic fatty liver disease rose steadily across the entire study period with a SAPC of 6.79 (95% CI: 6.3-7.3, p<0.001). The decreasing trend of HCV-related mortality was reversed during the pandemic, while there was no significant change in HBV-related deaths. While there was significant increase in COVID-19-related deaths, more than 55% of the excess deaths were the indirect impact of the pandemic. We observed an alarming increase in cirrhosis-related deaths during the pandemic especially for ALD, with evidence in both direct and indirect impact. Our findings have implications on formulating policies for patients with cirrhosis.