Single-cell analysis of CD4+ tissue residency memory cells (TRMs) in adult atopic dermatitis: A new potential mechanism.

The pathophysiology of atopic dermatitis (AD) is complex. CD4+ T cells play an essential role in the development of lesions in AD. However, the underlying mechanism remains unclear. In the present study, we investigated the differentially expressed genes (DEGs) between adult AD lesioned and non-lesioned skin using two datasets from the Gene Expression Omnibus (GEO) database. 62 DEGs were shown to be related to cytokine response. Compared to non-lesioned skin, lesioned skin showed immune infiltration with increased numbers of activated natural killer (NK) cells and CD4+ T memory cells (p < 0.01). We then identified 13 hub genes with a strong association with CD4+ T cells using weighted correlation network analysis. Single-cell analysis of AD detected a novel CD4+ T subcluster, CD4+ tissue residency memory cells (TRMs), which were verified through immunohistochemistry (IHC) to be increased in the dermal area of AD. The significant relationship between CD4+ TRM and AD was assessed through further analyses. FOXO1 and SBNO2, two of the 13 hub genes, were characteristically expressed in the CD4+ TRM, but down-regulated in IFN-γ/TNF-α-induced HaCaT cells, as shown using quantitative polymerase chain reaction (qPCR). Moreover, SBNO2 expression was associated with increased Th1 infiltration in AD (p < 0.05). In addition, genes filtered using Mendelian randomization were positively correlated with CD4+ TRM and were highly expressed in IFN-γ/TNF-α-induced HaCaT cells, as determined using qPCR and western blotting. Collectively, our results revealed that the newly identified CD4+ TRM may be involved in the pathogenesis of adult AD.

Vapor Phase Growth of Air-Stable Hybrid Perovskite FAPbBr3 Single-Crystalline Nanosheets.

Organic-inorganic hybrid perovskites have attracted tremendous attention owing to their fascinating optoelectronic properties. However, their poor air stability seriously hinders practical applications, which becomes more serious with thickness down to the nanoscale. Here we report a one-step vapor phase growth of HC(NH2)2PbBr3 (FAPbBr3) single-crystalline nanosheets of tunable size up to 50 µm and thickness down to 20 nm. The FAPbBr3 nanosheets demonstrate high stability for over months of exposure to air with no degradation in surface roughness and photoluminescence efficiency. Besides, the FAPbBr3 photodetectors exhibit superior overall performance as compared to previous devices based on nonlayered perovskite nanosheets, such as an ultralow dark current of 24 pA, an ultrahigh responsivity of 1033 A/W, an external quantum efficiency over 3000%, a rapid response time around 25 ms, and a high on/off ratio of 104. This work provides a strategy to tackle the challenges of hybrid perovskites toward integrated optoelectronics with requirements of nanoscale thickness, high stability, and excellent performance.

Polyamine biosynthesis and eIF5A hypusination are modulated by the DNA tumor virus KSHV and promote KSHV viral infection.

Polyamines are critical metabolites involved in various cellular processes and often dysregulated in cancers. Kaposi's sarcoma-associated Herpesvirus (KSHV), a defined human oncogenic virus, leads to profound alterations of host metabolic landscape to favor development of KSHV-associated malignancies. In our studies, we identified that polyamine biosynthesis and eIF5A hypusination are dynamically regulated by KSHV infection through modulation of key enzymes (ODC1 and DHPS) of these pathways. During KSHV latency, ODC1 and DHPS are upregulated along with increase of hypusinated eIF5A (hyp-eIF5A), while hyp-eIF5A is further induced along with reduction of ODC1 and intracellular polyamines during KSHV lytic reactivation. In return these metabolic pathways are required for both KSHV lytic reactivation and de novo infection. Further analysis unraveled that synthesis of critical KSHV latent and lytic proteins (LANA, RTA) depends on hypusinated-eIF5A. We also demonstrated that KSHV infection can be efficiently and specifically suppressed by inhibitors targeting these pathways. Collectively, our results illustrated that the dynamic and profound interaction of a DNA tumor virus (KSHV) with host polyamine biosynthesis and eIF5A hypusination pathways promote viral propagation, thus defining new therapeutic targets to treat KSHV-associated malignancies.

Accumulation of advanced glycation end products promotes atrophic nonunion incidence in mice through a CtBP1/2-dependent mechanism.

Atrophic nonunion (AN) is a complex and poorly understood pathological condition resulting from impaired fracture healing. Advanced glycation end products (AGEs) have been implicated in the pathogenesis of several bone disorders, including osteoporosis and osteoarthritis. However, the role of AGEs in the development of AN remains unclear. This study found that mice fed a high-AGE diet had a higher incidence of atrophic nonunion (AN) compared to mice fed a normal diet following tibial fractures. AGEs induced two C-terminal binding proteins (CtBPs), CtBP1 and CtBP2, which were necessary for the development of AN in response to AGE accumulation. Feeding a high-AGE diet after fracture surgery in CtBP1/2-/- and RAGE-/- (receptor of AGE) mice did not result in a significant occurrence of AN. Molecular investigation revealed that CtBP1 and CtBP2 formed a heterodimer that was recruited by histone deacetylase 1 (HDAC1) and runt-related transcription factor 2 (Runx2) to assemble a complex. The CtBP1/2-HDAC1-Runx2 complex was responsible for the downregulation of two classes of bone development and differentiation genes, including bone morphogenic proteins (BMPs) and matrix metalloproteinases (MMPs). These findings demonstrate that AGE accumulation promotes the incidence of AN in a CtBP1/2-dependent manner, possibly by modulating genes related to bone development and fracture healing. These results provide new insights into the pathogenesis of AN and suggest new therapeutic targets for its prevention and treatment.

FACT subunit SUPT16H associates with BRD4 and contributes to silencing of interferon signaling.

FACT (FAcilitates Chromatin Transcription) is a heterodimeric protein complex composed of SUPT16H and SSRP1, and a histone chaperone participating in chromatin remodeling during gene transcription. FACT complex is profoundly regulated, and contributes to both gene activation and suppression. Here we reported that SUPT16H, a subunit of FACT, is acetylated in both epithelial and natural killer (NK) cells. The histone acetyltransferase TIP60 contributes to the acetylation of SUPT16H middle domain (MD) at lysine 674 (K674). Such acetylation of SUPT16H is recognized by bromodomain protein BRD4, which promotes protein stability of SUPT16H in both epithelial and NK cells. We further demonstrated that SUPT16H-BRD4 associates with histone modification enzymes (HDAC1, EZH2), and further regulates their activation status and/or promoter association as well as affects the relevant histone marks (H3ac, H3K9me3 and H3K27me3). BRD4 is known to profoundly regulate interferon (IFN) signaling, while such function of SUPT16H has never been explored. Surprisingly, our results revealed that SUPT16H genetic knockdown via RNAi or pharmacological inhibition by using its inhibitor, curaxin 137 (CBL0137), results in the induction of IFNs and interferon-stimulated genes (ISGs). Through this mechanism, depletion or inhibition of SUPT16H is shown to efficiently inhibit infection of multiple viruses, including Zika, influenza, and SARS-CoV-2. Furthermore, we demonstrated that depletion or inhibition of SUPT16H also causes the remarkable activation of IFN signaling in NK cells, which promotes the NK-mediated killing of virus-infected cells in a co-culture system using human primary NK cells. Overall, our studies unraveled the previously un-appreciated role of FACT complex in coordinating with BRD4 and regulating IFN signaling in both epithelial and NK cells, and also proposed the novel application of the FACT inhibitor CBL0137 to treat viral infections.

Cooperation of Different Active Sites to Promote CO2 Electroreduction to Multi-carbon Products at Ampere-Level.

Electroreduction of CO2 to C2+ products provides a promising strategy for reaching the goal of carbon neutrality. However, achieving high selectivity of C2+ products at high current density remains a challenge. In this work, we designed and prepared a multi-sites catalyst, in which Pd was atomically dispersed in Cu (Pd-Cu). It was found that the Pd-Cu catalyst had excellent performance for producing C2+ products from CO2 electroreduction. The Faradaic efficiency (FE) of C2+ products could be maintained at approximately 80.8 %, even at a high current density of 0.8 A cm-2 for at least 20 hours. In addition, the FE of C2+ products was above 70 % at 1.4 A cm-2. Experiments and density functional theory (DFT) calculations revealed that the catalyst had three distinct catalytic sites. These three active sites allowed for efficient conversion of CO2, water dissociation, and CO conversion, ultimately leading to high yields of C2+ products.

Adjacent Copper Single Atoms Promote C-C Coupling in Electrochemical CO2 Reduction for the Efficient Conversion of Ethanol.

The electrochemical CO2 reduction reaction (CO2RR) using renewable electricity is one of the most promising strategies for reaching the goal of carbon neutrality. Multicarbonous (C2+) products have broad applications, and ethanol is a valuable chemical and fuel. Many Cu-based catalysts have been reported to be efficient for the electrocatalytic CO2RR to C2+ products, but they generally offer limited selectivity and current density toward ethanol. Herein, we proposed a silica-mediated hydrogen-bonded organic framework (HOF)-templated approach to preparing ultrahigh-density Cu single-atom catalysts (SACs) on thin-walled N-doped carbon nanotubes (TWN). The content of Cu in the catalysts prepared by this method could be up to 13.35 wt %. It was found that the catalysts showed outstanding performance for the electrochemical CO2RR to ethanol, and the Faradaic efficiency (FE) of ethanol increased with the increase in Cu-N3 site density. The FE of ethanol over the catalysts with 13.35 wt % Cu could reach ∼81.9% with a partial current density of 35.6 mA cm-2 using an H-type cell, which is the best result for electrochemical CO2RR to ethanol to date. In addition, the catalyst could be stably used for more than 25 h. Experimental and density functional theory (DFT) studies revealed that the adjacent Cu-N3 active sites (one Cu atom coordinates with three N) were the active sites for the reaction, and their high density was crucial for the high FE of ethanol because the adjacent Cu-N3 sites with a short distance could promote the C-C coupling synergistically.

A Droplet Method for Synthesis of Multiclass Ultrathin Metal Halides.

2D metal halides have attracted increasing research attention in recent years; however, it is still challenging to synthesize them via liquid-phase methods. Here it is demonstrated that a droplet method is simple and efficient for the synthesis of multiclass 2D metal halides, including trivalent (BiI3 , SbI3 ), divalent (SnI2 , GeI2 ), and monovalent (CuI) ones. In particular, 2D SbI3 is first experimentally achieved, of which the thinnest thickness is ≈6 nm. The nucleation and growth of these metal halide nanosheets are mainly determined by the supersaturation of precursor solutions that are dynamically varying during the solution evaporation. After solution drying, the nanosheets can fall on the surface of many different substrates, which further enables the feasible fabrication of related heterostructures and devices. With SbI3 /WSe2 being a good demonstration, the photoluminescence intensity and photo responsivity of WSe2 is obviously enhanced after interfacing with SbI3 . The work opens a new pathway for 2D metal halides toward widespread investigation and applications.

Inhibition of polo-like kinase 1 (PLK1) facilitates reactivation of gamma-herpesviruses and their elimination.

Both Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) establish the persistent, life-long infection primarily at the latent status, and associate with certain types of tumors, such as B cell lymphomas, especially in immuno-compromised individuals including people living with HIV (PLWH). Lytic reactivation of these viruses can be employed to kill tumor cells harboring latently infected viral episomes through the viral cytopathic effects and the subsequent antiviral immune responses. In this study, we identified that polo-like kinase 1 (PLK1) is induced by KSHV de novo infection as well as lytic switch from KSHV latency. We further demonstrated that PLK1 depletion or inhibition facilitates KSHV reactivation and promotes cell death of KSHV-infected lymphoma cells. Mechanistically, PLK1 regulates Myc that is critical to both maintenance of KSHV latency and support of cell survival, and preferentially affects the level of H3K27me3 inactive mark both globally and at certain loci of KSHV viral episomes. Furthremore, we recognized that PLK1 inhibition synergizes with STAT3 inhibition to efficiently induce KSHV reactivation. We also confirmed that PLK1 depletion or inhibition yields the similar effect on EBV lytic reactivation and cell death of EBV-infected lymphoma cells. Lastly, we noticed that PLK1 in B cells is elevated in the context of HIV infection and caused by HIV Nef protein to favor KSHV/EBV latency.

On the electroluminescence overshoot of quantum-dot light-emitting diodes.

The charge-carrier dynamics is a fundamental question in quantum-dot light-emitting diodes (QLEDs), determining the electroluminescence (EL) properties of the devices. By means of a hole-confined QLED design, the distribution and storage/residing of the charge carriers in the devices are deciphered by the transient electroluminescence (TrEL) spectroscopic technology. It is demonstrated that the holes stored in the quantum dots (QDs) are responsible for the EL overshoot during the rising edge of the TrEL response. Moreover, the earlier electroluminescence turn-on behavior is observed due to the holes residing in the hole-confined structure. The hole storage effect should be attributed to the ultralow hole mobility of QD films and large barrier for hole escape from the cores of the QDs. Our findings provide a deep understanding of the charge transport and storage at the most critical interface between QDs and hole-transport layer, where the excitons are formed.

Downregulation of circ-YES1 suppresses NSCLC migration and proliferation through the miR-142-3p-HMGB1 axis.

BACKGROUND: Circular RNAs (circRNAs) are a new family of abundant regulatory RNAs with roles in various types of cancer. While the hsa_circ_0046701 (circ-YES1) function in non-small cell lung cancer (NSCLC) is unclear. METHODS: Circ-YES1 expression in normal pulmonary epithelial and NSCLC cells was examined. The small interfering RNA for circ-YES1 was prepared, cell proliferation and migration were assessed. Tumorigenesis in nude mice was assayed to validate the role of circ-YES1. Bioinformatics analyses and luciferase reporter assays were utilized to identify downstream targets of circ-YES1. RESULTS: Compared to normal pulmonary epithelial cells, the circ-YES1 expression increased in NSCLC cells, and cell proliferation and migration were suppressed after circ-YES1 knockdown. Both high mobility group protein B1 (HMGB1) and miR-142-3p were found to be downstream targets of circ-YES1, and miR-142-3p inhibition and HMGB1 overexpression reversed the effects of circ-YES1 knockdown on cell proliferation and migration. Similarly, HMGB1 overexpression reversed the miR-142-3p overexpression effects on these two processes. The imaging experiment results revealed that circ-YES1 knockdown impeded tumor development and metastasis in a nude mouse xenograft model. CONCLUSION: Taken together, our results show that circ-YES1 promotes tumor development through the miR-142-3p-HMGB1 axis and support the development of circ-YES1 probability as a new therapeutic NSCLC target.

Association between rate of change in PaCO2 and functional outcome for patients with hypercapnia after out-of-hospital cardiac arrest: Secondary analysis of a randomized clinical trial.

BACKGROUND: Normocapnia is suggested for post resuscitation care. For patients with hypercapnia after cardiac arrest, the relationship between rate of change in partial pressure of carbon dioxide (PaCO2) and functional outcome was unknown. METHODS: This was the secondary analysis of Resuscitation Outcomes Consortium (ROC) amiodarone, lidocaine, and placebo (ALPS) trial. Patients with at least 2 PaCO2 recorded and the first indicating hypercapnia (PaCO2 > 45 mmHg) after return of spontaneous circulation (ROSC) were included. The rate of change in PaCO2 was calculated as the ratio of the difference between the second and first PaCO2 to the time interval. The primary outcome was modified Rankin Score (mRS), dichotomized to good (mRS 0-3) and poor (mRS 4-6) outcomes at hospital discharge. The independent relationship between rate of change in PaCO2 and outcome was investigated with multivariable logistic regression model. RESULTS: A total of 746 patients with hypercapnia were included for analysis, of which 264 (35.4%) patients had good functional outcome. The median rate of change in PaCO2 was 4.7 (interquartile range [IQR] 1.7-12) mmHg per hour. After adjusting for confounders, the rate of change in PaCO2 (odds ratio [OR] 0.994, confidence interval [CI] 0.985-1.004, p = 0.230) was not associated the functional outcome. However, rate of change in PaCO2 (OR 1.010, CI 1.001-1.019, p = 0.029) was independently associated with hospital mortality. CONCLUSIONS: For OHCA patients with hypercapnia on admission, the rate of change in PaCO2 was not independently associated with functional outcome; however, there was a significant trend that higher decreased rate was associated with increased hospital mortality.

Stimulating and Manipulating Robust Circularly Polarized Photoluminescence in Achiral Hybrid Perovskites.

Circularly polarized light (CPL) is essential for optoelectronic and chiro-spintronic applications. Hybrid perovskites, as star optoelectronic materials, have demonstrated CPL activity, which is, however, mostly limited to chiral perovskites. Here, we develop a simple, general, and efficient strategy to stimulate CPL activity in achiral perovskites, which possess rich species, efficient luminescence, and tunable bandgaps. With the formation of van der Waals heterojunctions between chiral and achiral perovskites, a nonequilibrium spin population and thus CPL activity are realized in achiral perovskites by receiving spin-polarized electrons from chiral perovskites. The polarization degree of room-temperature CPL in achiral perovskites is at least one order of magnitude higher than in chiral ones. The CPL polarization degree and emission wavelengths of achiral perovskites can be flexibly designed by tuning chemical compositions, operating temperature, or excitation wavelengths. We anticipate that unlimited types of achiral perovskites can be endowed with CPL activity, benefiting their applications in integrated CPL sources and detectors.

Structure, Stability, and Superconductivity of Two-Dimensional Janus NbSH Monolayers: A First-Principle Investigation.

Two-dimensional Janus materials have unique structural characteristics due to their lack of out-of-plane mirror symmetry, resulting in many excellent physical and chemical properties. Using first-principle calculations, we performed a detailed investigation of the possible stable structures and properties of two-dimensional Janus NbSH. We found that both Janus 1T and 2H structures are semiconductors, unlike their metallic counterparts MoSH. Furthermore, we predicted a new stable NbSH monolayer using a particle swarm optimization method combined with first-principle calculations. Interestingly, the out-of-plane mirror symmetry is preserved in this newly found 2D structure. Furthermore, the newly found NbSH is metallic and exhibits intrinsic superconducting behavior. The superconducting critical temperature is about 6.1 K under normal conditions, which is found to be very sensitive to stress. Even under a small compressive strain of 1.08%, the superconducting critical temperature increases to 9.3 K. In addition, the superconductivity was found to mainly originate from Nb atomic vibrations. Our results show the diversity of structures and properties of the two-dimensional Janus transition metal sulfhydrate materials and provide some guidelines for further investigations.

Excessive Iodine Enabled Ultrathin Inorganic Perovskite Growth at the Liquid-Air Interface.

The liquid-air interface offers a platform for the in-plane growth of free-standing materials. However, it is rarely used for inorganic perovskites and ultrathin non-layered perovskites. Herein the liquid-air interfacial synthesis of inorganic perovskite nanosheets (Cs3 Bi2 I9 , Cs3 Sb2 I9 ) is achieved simply by drop-casting the precursor solution with only the addition of iodine. The products are inaccessible without iodine addition. The thickness and lateral size of these nanosheets can be adjusted through the iodine concentration. The high volatility of the iodine spontaneously drives precursors that normally stay in the liquid to the liquid-air interface. The iodine also repairs in situ iodine vacancies during perovskite growth, giving enhanced optical and optoelectronic properties. The liquid-air interfacial growth of ultrathin perovskites provides multi-degree-of-freedom for constructing perovskite-based heterostructures and devices at atomic scale.

Lithographic Multicolor Patterning on Hybrid Perovskites for Nano-Optoelectronic Applications.

Ultrathin hybrid perovskites, with exotic properties and two-dimensional geometry, exhibit great potential in nanoscale optical and optoelectronic devices. However, it is still challenging for them to be compatible with high-resolution patterning technology toward miniaturization and integration applications, as they can be readily damaged by the organic solvents used in standard lithography processes. Here, a flexible three-step method is developed to make high-resolution multicolor patterning on hybrid perovskite, particularly achieved on a single nanosheet. The process includes first synthesis of precursor PbI2 , then e-beam lithography and final conversion to target perovskite. The patterns with linewidth around 150 nm can be achieved, which can be applied in miniature optoelectronic devices and high-resolution displays. As an example, the channel length of perovskite photodetectors can be down to 126 nm. Through deterministic vapor-phase anion exchange, a perovskite nanosheet can not only gradually alter the color of the same pattern in a wide wavelength range, but also display different colors simultaneously. The authors are optimistic that the method can be applied for unlimited perovskite types and device configurations for their high-integrated miniature applications.

Nucleolar protein NOP2/NSUN1 suppresses HIV-1 transcription and promotes viral latency by competing with Tat for TAR binding and methylation.

Recent efforts have been paid to identify previously unrecognized HIV-1 latency-promoting genes (LPGs) that can potentially be targeted for eradication of HIV-1 latent reservoirs. From our earlier orthologous RNAi screens of host factors regulating HIV-1 replication, we identified that the nucleolar protein NOP2/NSUN1, a m5C RNA methyltransferase (MTase), is an HIV-1 restriction factor. Loss- and gain-of-function analyses confirmed that NOP2 restricts HIV-1 replication. Depletion of NOP2 promotes the reactivation of latently infected HIV-1 proviruses in multiple cell lines as well as primary CD4+ T cells, alone or in combination with latency-reversing agents (LRAs). Mechanistically, NOP2 associates with HIV-1 5' LTR, interacts with HIV-1 TAR RNA by competing with HIV-1 Tat protein, as well as contributes to TAR m5C methylation. RNA MTase catalytic domain (MTD) of NOP2 mediates its competition with Tat and binding with TAR. Overall, these findings verified that NOP2 suppresses HIV-1 transcription and promotes viral latency.

Profiling of immune related genes silenced in EBV-positive gastric carcinoma identified novel restriction factors of human gammaherpesviruses.

EBV-associated gastric cancer (EBVaGC) is characterized by high frequency of DNA methylation. In this study, we investigated how epigenetic alteration of host genome contributes to pathogenesis of EBVaGC through the analysis of transcriptomic and epigenomic datasets from NIH TCGA (The Cancer Genome Atlas) consortium. We identified that immune related genes (IRGs) is a group of host genes preferentially silenced in EBV-positive gastric cancers through DNA hypermethylation. Further functional characterizations of selected IRGs reveal their novel antiviral activity against not only EBV but also KSHV. In particular, we showed that metallothionein-1 (MT1) and homeobox A (HOXA) gene clusters are down-regulated via EBV-driven DNA hypermethylation. Several MT1 isoforms suppress EBV lytic replication and release of progeny virions as well as KSHV lytic reactivation, suggesting functional redundancy of these genes. In addition, single HOXA10 isoform exerts antiviral activity against both EBV and KSHV. We also confirmed the antiviral effect of other dysregulated IRGs, such as IRAK2 and MAL, in scenario of EBV and KSHV lytic reactivation. Collectively, our results demonstrated that epigenetic silencing of IRGs is a viral strategy to escape immune surveillance and promote viral propagation, which is overall beneficial to viral oncogenesis of human gamma-herpesviruses (EBV and KSHV), considering that these IRGs possess antiviral activities against these oncoviruses.

Early coagulopathy after pediatric out-of-hospital cardiac arrest: secondary analysis of a randomized clinical trial.

BACKGROUND: To estimate the incidence, risk factors, and impact on mortality and functional outcomes for early coagulopathy after the return of spontaneous circulation (ROSC) in pediatric out-of-hospital cardiac arrest (OHCA) patients. METHODS: A post hoc analysis of the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial was conducted. Early coagulopathy was defined as presence of at least one of the following coagulation abnormalities upon admission: international standard ratio (INR), platelets, and age-adjusted activated partial thromboplastin time (APTT) within 6 h after OHCA and before therapeutic hypothermia initiation. The outcomes included 28-day mortality and functional prognosis. Multivariable logistic regression models were used to explore risk factors and association between early coagulopathy and outcomes. RESULTS: Of the 227 patients included, 152 (67%) were male and the median age was 2.3 years [interquartile range (IQR), 0.7-8.6 years]. The overall 28-day mortality was 63%. The incidence of early coagulopathy was 46%. Lower age, longer duration of chest compression, lower temperature, and higher white blood cell (WBC) upon admission increased the risk of early coagulopathy. Early coagulopathy [OR, 2.20 (95% CI, 1.12-4.39), P = 0.023] was independently associated with 28-day mortality after adjusting for confounders. CONCLUSIONS: Early coagulopathy occurred in almost half of pediatric patients with OHCA. Lower age, longer duration of chest compression, lower temperature, and higher WBC increased the risk. The development of early coagulopathy was independently associated with increased mortality.

The obesity paradox for survivors of critically ill patients.

The obesity paradox has been observed in short-term outcomes from critical illness. However, little is known regarding the impact of obesity on long-term outcomes for survivors of critically ill patients. We aimed to evaluate the influence of obesity on long-term mortality outcomes after discharge alive from ICU. The adult patients who were discharged alive from the last ICU admission were extracted. After exclusion, a total of 7619 adult patients discharged alive from ICU were included, with 4-year mortality of 32%. The median body mass index (BMI) was 27.2 (IQR 24-31.4) kg/m2, and 2490 (31.5%) patients were classified as obese or morbidly obese. The morbidly obese patients had the highest ICU and hospital length of stay. However, higher BMI was associated with lower hazard ratio for 4-year mortality. The results showed the obesity paradox may be also suitable for survivors of critically ill patients.