Maternal circadian rhythm disruption affects neonatal inflammation via metabolic reprograming of myeloid cells.

Disruption of circadian rhythm during pregnancy produces adverse health outcomes in offspring; however, the role of maternal circadian rhythms in the immune system of infants and their susceptibility to inflammation remains poorly understood. Here we show that disruption of circadian rhythms in pregnant mice profoundly aggravates the severity of neonatal inflammatory disorders in both male and female offspring, such as necrotizing enterocolitis and sepsis. The diminished maternal production of docosahexaenoic acid (DHA) and the impaired immunosuppressive function of neonatal myeloid-derived suppressor cells (MDSCs) contribute to this phenomenon. Mechanistically, DHA enhances the immunosuppressive function of MDSCs via PPARγ-mediated mitochondrial oxidative phosphorylation. Transfer of MDSCs or perinatal supplementation of DHA relieves neonatal inflammation induced by maternal rhythm disruption. These observations collectively demonstrate a previously unrecognized role of maternal circadian rhythms in the control of neonatal inflammation via metabolic reprograming of myeloid cells.

Neonicotinoid insecticides and metabolites levels in neonatal first urine from southern China: Exploring links to preterm birth.

Neonicotinoids (NEOs) have indeed become the most widely used insecticides worldwide. Concerns have been raised about their potential impact on newborns due to maternal exposure and their unique neurotoxic mode of action. However, it is still poorly understood whether in utero exposure of pregnant women to environmental NEOs and their metabolites can cause carryover effects on vulnerable newborns and subsequent health consequences. In this study, we determined the concentrations of 13 NEOs and their metabolites in the first urine collected from 92 newborns, both preterm and full-term, in southern China during 2020 and 2021. NEOs and their metabolites were identified in 91 urine samples, with over 93% of samples containing a cocktail of these compounds, confirming their maternal-fetal transfer. N-desmethyl-acetamiprid, imidaclothiz, clothianidin and flonicamid were the most commonly detected analytes, with detection frequencies of 59-87% and medians of 0.024-0.291 ng/mL in the urine. The relative abundance of imidaclothiz was significantly higher in preterm newborns, those with head circumferences below 33 cm, birth lengths less than 47 cm, and weights below 2500 g (p < 0.05). When comparing newborns in the 2nd quartile of imidaclothiz concentrations with those in the 1st quartile, we observed a significant increase in the odds of preterm outcomes in the unadjusted model (odds ratio = 3.24, 95% confidence interval = 1.02-10.3). These results suggest that exposure to elevated concentrations of imidaclothiz may be associated with preterm birth.

iASPP regulates neurite development by interacting with Spectrin proteins.

Introduction: Since its discovery in 1999, a substantial body of research has shown that iASPP is highly expressed in various kinds of tumors, interacts with p53, and promotes cancer cell survival by antagonizing the apoptotic activity of p53. However, its role in neurodevelopment is still unknown. Methods: We studied the role of iASPP in neuronal differentiation through different neuronal differentiation cellular models, combined with immunohistochemistry, RNA interference and gene overexpression, and studied the molecular mechanism involved in the regulation of neuronal development by iASPP through coimmunoprecipitation coupled with mass spectrometry (CoIP-MS) and coimmunoprecipitation (CoIP). Results: In this study, we found that the expression of iASPP gradually decreased during neuronal development. iASPP silencing promotes neuronal differentiation, while its overexpression inhibited neurite differentiation in a variety of neuronal differentiation cellular models. iASPP associated with the cytoskeleton-related protein Sptan1 and dephosphorylated the serine residues in the last spectrin repeat domain of Sptan1 by recruiting PP1. The non-phosphorylated and phosphomimetic mutant form of Sptbn1 inhibited and promoted neuronal cell development respectively. Conclusion: Overall, we demonstrate that iASPP suppressed neurite development by inhibiting phosphorylation of Sptbn1.

Advances in Understanding the Molecular Mechanisms of Neuronal Polarity.

The establishment and maintenance of neuronal polarity are important for neural development and function. Abnormal neuronal polarity establishment commonly leads to a variety of neurodevelopmental disorders. Over the past three decades, with the continuous development and improvement of biological research methods and techniques, we have made tremendous progress in the understanding of the molecular mechanisms of neuronal polarity establishment. The activity of positive and negative feedback signals and actin waves are both essential in this process. They drive the directional transport and aggregation of key molecules of neuronal polarity, promote the spatiotemporal regulation of ordered and coordinated interactions of actin filaments and microtubules, stimulate the specialization and growth of axons, and inhibit the formation of multiple axons. In this review, we focus on recent advances in these areas, in particular the important findings about neuronal polarity in two classical models, in vitro primary hippocampal/cortical neurons and in vivo cortical pyramidal neurons, and discuss our current understanding of neuronal polarity.​.

Efficient degradation of clothianidin and thiamethoxam in contaminated soil by peroxymonosulfate process.

The widespread use of neonicotinoids has led to their frequent detection in the environment and potential environmental risk in recent years. Clothianidin (CLO) and thiamethoxam (TMX), as the second generation of neonicotinoid insecticides, are usually used as seed agents with a high risk of residue in the soil. Efficient degradation of CLO and TMX in soil using peroxymonosulfate (PMS) process was investigated in the present study. The degradation efficiencies of CLO and TMX reached 91.4% and 98.6% in 60 min with the addition of 20 mM PMS at pH 5.5 and 25℃. High degradation efficiencies of CLO were achieved with a high PMS dosage and temperature or a low CLO concentration and initial pH. The degradation of CLO was reduced in the presence of high concentration of inorganic anions (Cl-, HCO3-). Soil organic matter might be one critical factor in the degradation of CLO and TMX. Radical scavenger experiments confirmed SO4•- and 1O2 were the dominant reactive species on the CLO and TMX degradation. Based on the detected degradation intermediates, the degradation pathways of CLO and TMX include dichlorination, hydroxylation, cleavage of C-N or C-C bond and further oxidation in the PMS-based soil. Overall, the PMS process is one effective and economical method for the remediation of the neonicotinoid contaminated soil.

Molecular Mechanisms Involved in the Regulation of Neurodevelopment by miR-124.

miR-124 is a miRNA predominantly expressed in the nervous system and accounts for more than a quarter of the total miRNAs in the brain. It regulates neurogenesis, neuronal differentiation, neuronal maturation, and synapse formation and is the most important miRNA in the brain. Furthermore, emerging evidence has suggested miR-124 may be associated with the pathogenesis of various neurodevelopmental and neuropsychiatric disorders. Here, we provide an overview of the role of miR-124 in neurodevelopment and the underling mechanisms, and finally, we prospect the significance of miR-124 research to the field of neuroscience.

Causal relationship between gut microbiota and kidney diseases: a two-sample Mendelian randomization study.

Background: The interplay between gut microbiome genera and inflammatory kidney-related diseases, such as nephrotic syndrome, glomerulonephritis, tubulo-interstitial nephritis, and chronic kidney disease, has been observed. However, the causal relationships between specific bacterial genera and these renal diseases have not been fully elucidated. Objective: To investigate the potential causal links between different genera of the gut microbiome and the susceptibility to various renal conditions utilizing two-sample Mendelian randomization (MR) analyses. Materials and methods: Genome-wide association study (GWAS) summary statistics of gut microbiota and inflammatory kidney-related diseases were obtained from published GWASs. Two-sample MR analyses were conducted using methods including inverse-variance weighted (IVW), MR Egger, and others to identify potential causal links between gut microbial genera and renal conditions. Sensitivity analyses, including Cochran's Q test and the MR-PRESSO global test, were performed to validate the robustness of the results and detect horizontal pleiotropy. In addition, a reverse MR analysis was conducted to assess reverse causation possibilities. Results: By synthesizing insights from both primary and sensitivity analyses, this study unveiled critical associations of 12 bacterial genera with nephrotic syndrome, 7 bacterial genera with membranous nephropathy, 3 bacterial genera with glomerulonephritis, 4 bacterial genera with acute tubulo-interstitial nephritis, 6 bacterial genera with chronic tubulo-interstitial nephritis, and 7 bacterial genera with chronic kidney disease. Various genera were pinpointed as having either positive or negative causal relationships with these renal conditions, as evidenced by specific ranges of IVW-OR values (all P< 0.05). The congruence of the sensitivity analyses bolstered the primary findings, displaying no marked heterogeneity or horizontal pleiotropy. Notably, the reverse MR analysis with nephritis as the exposure did not reveal any causal relationships, thereby strengthening the resilience and validity of the primary associations. Conclusion: This study explored the causal associations between several gut microbial genera and the risk of several inflammatory kidney-related diseases, uncovering several associations between specific gut microbial genera and nephrotic syndrome, membranous nephropathy, glomerulonephritis, tubulo-interstitial nephritis, and chronic kidney disease. These findings enhance our understanding of the complex interplay between the gut microbiome and kidney diseases, and they will be beneficial for early diagnosis and subsequent treatment.

Apgar scores correlate with survival rate at discharge in extremely preterm infants with gestational age of 25-27 weeks.

Low Apgar score is associated with increased risk of death in preterm or full-term infants. However, the use of Apgar score to assess extremely preterm (EP) infants is controversial. In this study, we characterized the distribution of Apgar scores in EP infants with gestational age between 25 and 27 weeks, and investigated the association of Apgar score with survival rate at discharge by analyzing the clinical data of the EP infants discharged between January 2008 and December 2017 from 26 neonatal intensive care units in Guangdong Province, China. A total of 1567 infants with gestational age of 26.84±0.79 weeks and birth weight of 951±169 grams were involved in our study. The Apgar score increased with gestational age from 25 to 27 weeks and with time from birth from 1 to 10 min. The survival rate increased with a higher Apgar score, but no significant difference was found for 1-min Apgar score and the survival rate between infants with 25 or 26 weeks of gestation or 5-min Apgar score in infants with 25 weeks of gestation. The Apgar score is associated with survival of EP infants.

Efficient degradation of imidacloprid in soil by thermally activated persulfate process: Performance, kinetics, and mechanisms.

Imidacloprid (IMI) as a first-generation commercial neonicotinoid has been frequently detected in the environment in recent years. In this study, the efficient degradation of IMI in soil by a thermally activated persulfate (PS) process was investigated. The degradation efficiencies of IMI were in the range of 82-97% with the PS dosage of 10 mM, when the initial concentrations of IMI were 5-50 mg/kg in the soil. Degradation of the IMI was fitted with a pseudo-first-order kinetic model under different reaction temperatures. Inhibition effects of the common inorganic anions on the IMI degradation in the system followed the order Cl- > HCO3- > H2PO4- > NO3-. Soil pH and soil organic matter were also main factors affecting the degradation of IMI. The degradation efficiencies (64-97%) of three other typical neonicotinoids (acetamiprid, clothianidin, and dinotefuran) indicated that the thermally activated persulfate process could be used for remediation of neonicotinoid-contaminated soil. Quenching experiments indicated that the major reactive species in IMI degradation were SO4•-, O2•-, and •OH. Six degradation intermediates of IMI were inferred in the soil, and degradation pathways of IMI included hydroxylation, denitrification, C-N bond break and further oxidation.

Mothers with hypertensive disorders of pregnancy increased risk of periventricular leukomalacia in extremely preterm or extremely low birth weight infants: A propensity score analysis.

Background: At present, the conclusions about the impact of hypertensive disorders of pregnancy (HDP) on the clinical outcomes of preterm infants are inconsistent. This study used the propensity score matching (PSM) analysis to evaluate the effect of HDP on clinical outcomes of extremely preterm or extremely low birth weight (EP/ELBW) infants. Methods: Retrospective analysis was performed on the EP/ELBW infants discharged from 26 tertiary neonatal intensive care units or died during hospitalization from 2008 to 2017, who were divided into HDP group and non-HDP group. The six covariates including sex, gestational age, birth weight, twin or multiple pregnancy, antenatal steroids administration, and conception method were matched through the PSM method at a ratio of 1:1. The survival rate at discharge and the major clinical complications were compared between the two groups. Results: After matching the six covariates, compared with the non-HDP group, there was no significant difference in the survival rate at discharge (64 vs. 63.2%, p > 0.05), the incidence of bronchopulmonary dysplasia (BPD) or moderate to severe BPD in the HDP group (58.3 vs. 54.9%, p > 0.05; 5.2 vs. 6.2%, p > 0.05). The incidence of periventricular leukomalacia (PVL) in the HDP group was significantly increased (5.7 vs. 1.9%, p < 0.05). Conclusions: HDP increased the risk of PVL in EP/ELBW infants, but had no significant effect on the survival rate at discharge, or the occurrence of other complications.

Early evaluation of adjuvant effects on topramezone efficacy under different temperature conditions using chlorophyll fluorescence tests.

Proper selection of adjuvant applications is an important strategy to enhance herbicide efficacy and reduce active ingredient input especially under adverse environmental conditions. In this study, a two-factor split-plot-design experiment was conducted to evaluate the effects of two adjuvants on the efficacy of topramezone on the grassy weed species giant foxtail (Setaria faberi Herrm.) and the broadleaved weed species velvetleaf (Abutilon theophrasti Medik.) under three different temperature conditions. The two tested adjuvants were methylated seed oil (MSO) and organosilicone. Three temperature levels, 35/30°C, 25/20°C, and 15/10°C (day/night), were used in the laboratory and greenhouse experiment. Plant chlorophyll fluorescence measurements shortly after herbicide application and classic whole-plant bioassay methods were used to evaluate the herbicide efficacy among the different treatments. Results indicated that the maximum quantum efficiency (Fv/Fm) of the top leaf of the weeds treated with topramezone mixed with MSO was significantly lower than that of the weeds treated with topramezone mixed with organosilicone and without an adjuvant at 2-3 days after treatment under all three temperature levels. The herbicide response of the plants treated with topramezone mixed with organosilicone and topramezone alone was not significantly different. These results corresponded well with the results of the classic whole-plant test. MSO has been shown to be good at enhancing the efficacy of topramezone on these weed species under all three temperature conditions. The measurement of chlorophyll fluorescence is a promising technique for evaluating the effects of adjuvants on the efficacy of herbicides shortly after herbicide treatment.

Short term outcomes of extremely low birth weight infants from a multicenter cohort study in Guangdong of China.

With the increase in extremely low birth weight (ELBW) infants, their outcome attracted worldwide attention. However, in China, the related studies are rare. The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units in Guangdong Province of China during 2008-2017 were analyzed. A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76% to 62.02%. Increased survival is closely related to birth weight (BW), regional economic development, and specialized hospital. The incidence of complications was neonatal respiratory distress syndrome (85.2%), oxygen dependency at 28 days (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days). A total of 768 ELBW infants died after treatment withdrawal, for reasons of economic and/or poor outcome. The number of ELBW infants is increasing in Guangdong Province of China, and the overall survival rate is improving steadily.

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OBJECTIVES: To study the effect of sex on the clinical outcome of extremely preterm infants (EPIs)/extremely low birth weight infants (ELBWIs) by propensity score matching. METHODS: A retrospective analysis was performed for the medical data of 731 EPIs or ELBWIs who were admitted from January 1, 2011 to December 31, 2020. These infants were divided into two groups: male and female. A propensity score matching analysis was performed at a ratio of 1:1. The matching variables included gestational age, birth weight, percentage of withdrawal from active treatment, percentage of small-for-gestational-age infant, percentage of use of pulmonary surfactant, percentage of 1-minute Apgar score ≤3, percentage of mechanical ventilation, duration of mechanical ventilation, percentage of antenatal use of inadequate glucocorticoids, and percentage of hypertensive disorders in pregnancy. The two groups were compared in the incidence rate of main complications during hospitalization and the rate of survival at discharge. RESULTS: Before matching, compared with the female group, the male group had significantly higher incidence rates of neonatal respiratory distress syndrome, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and patent ductus arteriosus (P<0.05), while after matching, the male group only had a significantly higher incidence rate of BPD than the female group (P<0.05). There was no significant difference in the rate of survival at discharge between the two groups before and after matching (P>0.05). CONCLUSIONS: Male EPIs/ELBWIs have a higher risk of BPD than female EPIs/ELBWIs, but male and female EPIs/ELBWIs tend to have similar outcomes.

Increased Risk for Respiratory Complications in Male Extremely Preterm Infants: A Propensity Score Matching Study.

Background: Many factors can affect the clinical outcome of extremely premature infants (EPIs), but the effect of sex is paradoxical. This study used propensity score matching to adjust baseline information to reassess the clinical outcome of EPIs based on sex. Methods: A retrospective analysis was performed on EPIs admitted in the Department of Neonatology of the Third Affiliated Hospital of Guangzhou Medical University from 2011 to 2020. A propensity score matching (PSM) analysis was used to adjust the confounding factors including gestational age, birth weight, 1-minute Apgar score ≤ 3, withholding or withdrawing life-sustaining treatment(WWLST), mechanical ventilation, duration of mechanical ventilation, the mother with advanced age (≥35 years old), complete-course antenatal steroid therapy and hypertensive disorders of pregnancy. The survival rate at discharge and the incidence of major complications were evaluated between the male and female groups. Results: A total of 439 EPIs were included, and 240 (54.7%) infants were males. After matching the nine confounding factors, 148 pairs of infants were finally enrolled. There was no significant difference in the survival rate at discharge, as well as the mortality of activating treatment or WWLST between the two groups (all P>0.05). However, the incidence of respiratory distress syndrome, bronchopulmonary dysplasia (BPD), and moderate to severe BPD in the male group was significantly increased (all P<0.01), especially at birth weight between 750 and 999 grams. Conclusions: The male EPIs have a higher risk of respiratory complications than females, particularly at 750 to 999 grams of birth weight.

The inhibition of enterocyte proliferation by lithocholic acid exacerbates necrotizing enterocolitis through downregulating the Wnt/ß-catenin signalling pathway.

OBJECTIVES: Necrotizing enterocolitis (NEC) is a catastrophic gastrointestinal emergency in preterm infants, whose exact aetiology remains unknown. The role of lithocholic acid (LCA), a key component of secondary bile acids (BAs), in NEC is unclear. METHODS: Clinical data were collected to analyse the changes of BAs in NEC patients. In vitro studies, the cell proliferation and cell death were assessed. In vivo experiments, the newborn rats were administered with low or high dose of LCA and further induced NEC. RESULTS: Clinically, compared with control group, total BAs in the NEC patients were significantly higher when NEC occurred. In vitro, LCA treatment significantly inhibited the cell proliferation through arresting cell cycle at G1/S phase without inducing apoptosis or necroptosis. Mechanistically, the Wnt/ß-catenin pathway was involved. In vivo, LCA inhibited intestinal cell proliferation leading to disruption of intestinal barrier, and thereby increased the severity of NEC. Specifically, LCA supplementation caused higher levels of FITC-labelled dextran in serum, reduced PCNA expression and inhibited the activity of Wnt/ß-catenin pathway in enterocytes. The LC-MS/MS test found that LCA was significantly higher in intestinal tissue of NEC group, and more obviously in the NEC-L and NEC-H group compared with the DM group. CONCLUSION: LCA exacerbates NEC by inhibiting intestinal cell proliferation through downregulating the Wnt/ß-catenin pathway.

Insight into the uptake, accumulation, and metabolism of the fungicide phenamacril in lettuce (Lactuca sativa L.) and radish (Raphanus sativus L.).

The fungal species Fusarium can cause devastating disease in agricultural crops. Phenamacril is an extremely specific cyanoacrylate fungicide and a strobilurine analog that has excellent efficacy against Fusarium. To date, information on the mechanisms involved in the uptake, accumulation, and metabolism of phenamacril in plants is scarce. In this study, lettuce and radish were chosen as model plants for a comparative analysis of the absorption, accumulation, and metabolic characteristics of phenamacril from a polluted environment. We determined the total amount of phenamacril in the plant-water system by measuring the concentrations in the solution and plant tissues at frequent intervals over the exposure period. Phenamacril was readily taken up by the plant roots with average root concentration factor ranges of 60.8-172.7 and 16.4-26.9 mL/g for lettuce and radish, respectively. However, it showed limited root-to-shoot translocation. The lettuce roots had a 2.8-12.4-fold higher phenamacril content than the shoots; whereas the radish plants demonstrated the opposite, with the shoots having 1.5 to 10.0 times more phenamacril than the roots. By the end of the exposure period, the mass losses from the plant-water systems reached 72.0% and 66.3% for phenamacril in lettuce and radish, respectively, suggesting evidence of phenamacril biotransformation. Further analysis confirmed that phenamacril was metabolized via hydroxylation, hydrolysis of esters, demethylation, and desaturation reactions, and formed multiple transformation products. This study furthers our understanding of the fate of phenamacril when it passes from the environment to plants and provides an important reference for its scientific use and risk assessment.

Apgar scores correlate with survival rate at discharge in extremely preterm infants with gestational age of 25-27 weeks

Low Apgar score is associated with increased risk of death in preterm or full-term infants. However, the use of Apgar score to assess extremely preterm (EP) infants is controversial. In this study, we characterized the distribution of Apgar scores in EP infants with gestational age between 25 and 27 weeks, and investigated the association of Apgar score with survival rate at discharge by analyzing the clinical data of the EP infants discharged between January 2008 and December 2017 from 26 neonatal intensive care units in Guangdong Province, China. A total of 1567 infants with gestational age of 26.84±0.79 weeks and birth weight of 951±169 grams were involved in our study. The Apgar score increased with gestational age from 25 to 27 weeks and with time from birth from 1 to 10 min. The survival rate increased with a higher Apgar score, but no significant difference was found for 1-min Apgar score and the survival rate between infants with 25 or 26 weeks of gestation or 5-min Apgar score in infants with 25 weeks of gestation. The Apgar score is associated with survival of EP infants.

Efficacy and safety of surfactant administration via thin catheter in preterm infants with neonatal respiratory distress syndrome: A systematic review and meta-analysis.

OBJECTIVE: The efficacy and safety of surfactant administration via thin catheter in preterm infants with neonatal respiratory distress syndrome (NRDS) was investigated. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify randomized controlled trials (RCTs) that comparing thin catheter technique with intubation for surfactant delivery in preterm infants with NRDS. RESULTS: Thirteen RCTs (1931 infants) were included in the meta-analysis. The use of thin catheter technique decreased the incidences of bronchopulmonary dysplasia (BPD), pneumothorax, and hemodynamically significant patent ductus arteriosus (hsPDA) (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.46-0.75, p < .0001; RR: 0.60, 95% CI: 0.39-0.93, p = .02 and RR: 0.88, 95% CI: 0.78-1.00, p = .04, respectively). In addition, infants in the intervention group required less mechanical ventilation within 72 h of life or during hospitalization (RR: 0.60, 95% CI: 0.48-0.75, p < .00001 and RR: 0.64, 95% CI: 0.49-0.82, p = .0005, respectively) compared with infants in the control group. However, the rate of surfactant reflux was higher in the intervention group than that in the control group (RR: 2.12, 95% CI: 1.37-3.29, p = .0008). There were no significant differences in mortality and other outcomes between the two groups. CONCLUSION: The administration of surfactant via thin catheter could lower the requirement for mechanical ventilation, and decrease the incidence of BPD, pneumothorax, and hsPDA.

Analysis of the mTOR Interactome using SILAC technology revealed NICE-4 as a novel regulator of mTORC1 activity.

The evolutionarily conserved mechanistic target of rapamycin (mTOR) forms two functionally distinct complexes, -the mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2)-which differ in their subunit composition. Although the function of mTORC1 has been studied extensively, the interaction between mTORC1 and the ubiquitin-proteasome system (UPS) remains unclear. To facilitate a thorough understanding of the mechanismby which UPS regulates mTORC1 activity, steady isotope labeling with amino acids in cell culture (SILAC) technology was used to screen for potential mTORC1-interacting UPS members. Fourteen previously unknown proteins bound to mTOR in HEK293 cells with a SILAC ratio (heavy/light, H/L) above 2, five of which are components of the UPS. Subsequent immunoprecipitation analysis confirmed that ubiquitin-relevant protein 2-like (UBAP2L, also known as NICE-4) binds to both mTOR and Raptor, but not Rictor, suggesting that NICE-4 specifically interacts with mTORC1, but not mTORC2. Interestingly, NICE-4 is essential for basic mTORC1 activity in both HeLa cancer cells and HEK293 cells. In addition, NICE-4 depletion markedly suppressed proliferation of both HeLa and HEK293 cells as well as survival of HeLa cells. Collectively, these results revealed the identity of novel mTOR-interacting UPS proteins and established NICE-4 as a critical UPS member that maintains mTORC1 activity.