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Highlights • A 'red ring' circled an 'green ring' surrounding the black spot rot on jujubes. • Pathogenic infection is essential for the onset and development of the phenotype. • Individual phenolic compounds responded to A. alternata in peel and flesh tissues. • SA triggered the occurrence of the phenotype on A. alternata -infected jujubes. • SA increased phenolic acid, and enhanced PAL and C4H activities in jujubes. Abstract Alternaria alternata is the major threat to postharvest storage of jujube (Ziziphus jujuba Mill.) fruit. A typical phenotype that a 'red ring' circling an enclosed 'green ring' area surrounding the spot of Alternaria rot on the jujube peel was first found and investigated in this study. Results indicated that the pathogenic infection is essential for the onset and development of the phenotype on jujubes, with high inoculum concentration and low incubation temperature leading to the enlarged 'green ring'. The boundary line between the two rings seemed to be pre-fixed on the A. alternata -infected jujubes once the phenotype appeared. The 'green ring' was invaded gradually and 'eaten-up' eventually by the expansion of the surrounded rot spot. Biochemical measurements showed that such successful infection on jujubes might attribute to the great loss of individual phenolic compounds, including (+)-catechin, chlorogenic acid, (−)-epicatechin and p -coumaric acid, in the peel tissue of the 'green ring' and 'red ring', while some antifungal compounds increased in the flesh beneath the peel tissue in response to the infection. The elicitor salicylic acid (SA) triggered the early and rapid occurrence of the 'green ring' and 'red ring' on the A. alternata -infected jujubes. The SA treatment activated the phenylpropanoid pathway and elevated the accumulation of total phenolic compounds in the 'green ring' to combat the fungal attack and thereby restrict the expansion of disease lesion. Characterization of defense responses in the 'green ring' and 'red ring' on jujubes against Alternaria infection is helpful for unravelling the underlying mechanisms of the formation of defense resistance in fruit upon postharvest infection. [ABSTRACT FROM AUTHOR]

[Display omitted] • Significant altitudinal change of the needle, shoot, and stem growth traits was found. • Air temperature was the key factor driving the altitudinal change of organ growth. • The aboveground vegetative growth exhibits different temperature sensitivities. • Stem growth was more sensitive to temperature variation than needle and shoot growth. Although phenology and growth traits of leaves or woods have been the focus of research on growth-climate relationships, more is needed regarding whether there is a consistent growth response of different organs to environmental change. However, such work is crucial to accurately assess the impact of climate change on tree growth. Here, the growth timing, duration, rate, and increment of Picea meyeri needles, shoots, and stems were examined, and the corresponding environmental effects were revealed along an altitudinal gradient (2040–2740 m a.s.l.) in North-Central China during 2016 and 2017. The three organs showed a consistent altitudinal variation in growth onset timing, but a different variation in other traits; the growth duration, rate, and increment of needles changed slightly while those of shoots and stems dropped markedly with altitude. The air temperature was the key environmental factor driving the altitudinal variation. For each 1 °C increase in air temperature, the onset timing of needle and shoot elongation and xylem cell production was synchronously advanced by 3.3–3.7 ± 0.2 days; the peak timing was advanced by 3.4 ± 0.2 days, 2.2 ± 0.1 days, and 0 days; and the cessation timing was delayed by −3.8 ± 0.0 days, 2.1 ± 0.3 days, and 2.4 ± 0.1 days. Meanwhile, the duration was lengthened by 0 days, 5.6 ± 0.3 days, and 6.4 ± 0.2 days, respectively; the average rate was improved by 0%, 7.0 ± 1.2%, and 6.5 ± 0.5%, respectively; the increment was increased by 1.3 ± 0.1%, 8.2 ± 0.4%, and 11.0 ± 0.4%, respectively. These findings suggested that the aboveground vegetative growth of P. meyeri exhibits different temperature sensitivities; stem growth will benefit more from future warming than shoot and needle growth. It adds a new clue to conducting growth-climate relationship studies, and the response difference of organ growth to temperature should be considered in revealing future climate warming on tree growth. [ABSTRACT FROM AUTHOR]

Introduction: Transforming acidic coiled-coil containing protein 3 (TACC3) exerts a vital role in cancer progression by modulating cell division and facilitating tumor growth. Given the lack of comprehensive research on the pancancer implications of TACC3, our study aimed to analyze the functional role of TACC3 in pancancer and validate it through experimental investigations in lung adenocarcinoma. Methods: We first employed various bioinformatics techniques to investigate the expression and prognostic significance of TACC3 in pancancer. Subsequently, we analyzed the correlation between TACC3 and immune infiltration, immune checkpoints, drug sensitivity, as well as the prediction of immune therapy response. Finally, we validated the association between TACC3 and the proliferation of lung adenocarcinoma, as well as its resistance to docetaxel, through in vitro experiments. Results: Here, TACC3 exhibited high expression in human cancers and was associated with poor prognosis in various cancer types. It was also involved in immune infiltration and demonstrated a strong predictive ability for immune therapy response. Through drug sensitivity prediction, we further identified a potential association between TACC3 and docetaxel resistance, which was subsequently validated in lung adenocarcinoma. Conclusion: Our investigation of TACC3 revealed its potential as a promising target both for immunosuppression and docetaxel resistance in pancancer, especially in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Mesenchymal stromal cell (MSC)-based cell therapy is a promising approach for various inflammatory disorders based on their immunosuppressive capacity. Osteopontin (OPN) regulates several cellular functions including tissue repair, bone metabolism and immune reaction. However, the biological function of OPN in regulating the immunosuppressive capacity of MSCs remains elusive. Objectives: This study aims to highlight the underlying mechanism of the proinflammatory cytokines affect the therapeutic ability of MSCs through OPN. Methods: MSCs in response to the proinflammatory cytokines were collected to determine the expression profile of OPN. In vitro T-cell proliferation assays and gene editing were performed to check the role and mechanisms of OPN in regulating the immunosuppressive capacity of MSCs. Inflammatory disease mouse models were established to evaluate the effect of OPN on improving MSC-based immunotherapy. Results: We observed that OPN, including its two isoforms iOPN and sOPN, was downregulated in MSCs upon proinflammatory cytokine stimulation. Interestingly, iOPN, but not sOPN, greatly enhanced the immunosuppressive activity of MSCs on T-cell proliferation and thus alleviated the inflammatory pathologies of hepatitis and colitis. Mechanistically, iOPN interacted with STAT1 and mediated its deubiquitination, thereby inducing the master immunosuppressive mediator inducible nitric oxide synthase (iNOS) in MSCs. In addition, iOPN expression was directly downregulated by activated STAT1, which formed a negative feedback loop to restrain MSC immunosuppressive capacity. Conclusion: Our findings demonstrated that iOPN expression modulation in MSCs is a novel strategy to improve MSC-based immunotherapy. [ABSTRACT FROM AUTHOR]

Background and objective: Currently, the detection rates of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) in the blood cultures of neonates with sepsis exceed the national average drug resistance level, and vancomycin and linezolid are the primary antibacterial drugs used for these resistant bacteria according to the results of etiological examinations. However, a comprehensive evaluation of their costs and benefits in late-onset neonatal sepsis in a neonatal intensive care unit (NICU) has not been conducted. This study aimed to compare the cost and effectiveness of vancomycin and linezolid in treating neonatal sepsis in the NICU. Methods: A cost-effectiveness analysis of real-world data was carried out by retrospective study in our hospital, and the cost and effectiveness of vancomycin and linezolid were compared by establishing a decision tree model. The drug doses in the model were 0.6 g for linezolid and 0.5 g for vancomycin. The cost break down included cost of medical ward, NICU stay, intravenous infusion of vancomycin or linezolid, all monitoring tests, culture tests and drugs. The unit costs were sourced from hospital information systems. The effectiveness rates were obtained by cumulative probability analysis. One-way sensitivity analysis was used to analyze uncertain influencing factors. Results: The effectiveness rates of vancomycin and linezolid in treating neonatal sepsis in the NICU were 89.74% and 90.14%, respectively, with no significant difference. The average cost in the vancomycin group was ¥12261.43, and the average cost in the linezolid group was ¥17227.96. The incremental cost effectiveness was ¥12416.33 cost per additional neonate with treatment success in the linezolid group compared to vancomycin group at discharge. Factors that had the greatest influence on the sensitivity of the incremental cost-effectiveness ratio were the price of linezolid and the effectiveness rates. Conclusions: The cost for treatment success of one neonate in linezolid group was ¥5449.17 more than that in vancomycin group, indicating that vancomycin was more cost-effective. Therefore, these results can provide a reference for a cost effectiveness treatment scheme for neonatal sepsis in the NICU. [ABSTRACT FROM AUTHOR]

We report that circDDX21 functions as a sponge for miR-1264 and regulates QKI expression, thus repressing the progression of triple-negative breast cancer (TNBC). (O-P) The clone formation ability of the circDDX21 knockdown cells transfected with the miR-1264 inhibitor (*p < .05, **p < .01, ***p < .001) gl In previous study, miR-1264 was confirmed to be a target of another non-coding RNA, SOCS2-AS1. (Q and R) The clone formation ability of the miR-1264 inhibited cells transfected with QKI (*p < .05, **p < .01, ***p < .001) gl Thus far, we have confirmed that circDDX21 functions as a sponge for miR-1264, to regulate the expression of QKI. CircRNA DDX21 acts as a prognostic factor and sponge of miR-1264/QKI axis to weaken the progression of triple-negative breast cancer. [Extracted from the article]

Background: The aim of this study was to evaluate the influence of patient body mass index (BMI) and estimated creatinine clearance (CrCl) on serum vancomycin concentrations to define a possible optimal dosage regimen in overweight patients based on data obtained during therapeutic drug monitoring.Methods: This retrospective study used data collected from January 2017 to January 2019. Adult patients (n = 204) received vancomycin treatment at a dose of 1000 mg every 12 h and underwent serum monitoring. Data collected included patient disease category, sex, age, height, weight, vancomycin concentrations, and serum creatinine. The CrCl values were estimated using the Cockcroft-Gault formula. In this study, statistical comparisons were performed on the results of patients according to serum vancomycin concentration.Results: Serum vancomycin concentration was significantly related to BMI (P <  0.001) and CrCl (P <  0.05) in adult patients. Furthermore, the trough serum vancomycin concentration showed a logarithmic correlation with BMI (R = - 0.5108, 95% CI: - 0.6082 to - 0.3982, P <  0.001) and CrCl (R = - 0.5739, 95% CI: - 0.6616 to - 0.4707, P <  0.001). The multivariate analysis showed that BMI and CrCl are independent contributors to the trough vancomycin concentration. Moreover, some of the patients with higher BMI (≥ 24 kg/m2) met the goal trough concentration after an adjustment from 1000 mg every 12 h to 1000 mg every 8 h.Conclusions: Serum vancomycin concentration decreases progressively with increasing BMI and the augmentation in CrCl in adult patients. The trough concentration of vancomycin should be continuously monitored for patients with a BMI ≥ 24 kg/m2, and the dosage regimen should be adjusted to reach the target trough concentration in these patients to reduce the impact of BMI. [ABSTRACT FROM AUTHOR]

Fully and accurately studying temperature variations in montane areas are conducive to a better understanding of climate modeling and climate-growth relationships on regional scales. To explore the spatio-temporal changes in air and soil temperatures and their relationship in montane areas, on-site monitoring over 2 years (2015 and 2016) was conducted at nine different elevations from 2040 to 2740 m a.s.l. on Luya Mountain in the semiarid region of China. The results showed that the annual mean of air temperature lapse rate (ATLR) was 0.67 °C/100 m. ATLR varied obviously in different months within a range of 0.57~0.79 °C/100 m. The annual mean of the soil temperature lapse rate (STLR) was 0.48 °C/100 m. Seasonally, monthly mean soil temperature did not show a consistent pattern with regard to elevation. The relationships between air and soil temperatures showed piecewise changes. Soil was decoupled from the air temperature in cold winter and early spring. The parameters of the growing season based on the two temperature types had no corresponding relations, and seasonal mean of soil temperature showed the smallest value at mid-elevation rather than in the treeline ecotone. Based on these changes, our results emphasized that altitudinal and seasonal variability caused by local factors (such as snow cover and soil moisture) should be taken into full consideration in microclimate extrapolation and treeline prediction in montane areas, especially in relation to soil temperature. [ABSTRACT FROM AUTHOR]

Background: Ionizing radiation (IR) is one of the major clinical therapies of cancer, although it increases the epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC), unexpectedly. The cellular and molecular mechanisms underlying this role are not completely understood. Methods: We used NSCLC cell lines as well as tumor specimens from 78 patients with NSCLC to evaluate p53, Cathepsin L (CTSL) and EMT phenotypic changes. Xenograft models was also utilized to examine the roles of mutant p53 (mut-p53) and CTSL in regulating IR-induced EMT of NSCLC. Results: Expression of CTSL was markedly increased in human NSCLC tissues with mutant p53 (mut-p53), and p53 mutation positively correlated with metastasis of NSCLC patients. In human non-small cell lung cancer cell line, H1299 cells transfected with various p53 lentivirus vectors, mut-p53 could promote the invasion and motility of cells under IR, mainly through the EMT. This EMT process was induced by elevating intranuclear CTSL which was regulated by mut-p53 depending on Early growth response protein-1 (Egr-1) activation. In the subcutaneous tumor xenograft model, IR promoted the EMT of the cancer cells in the presence of mut-p53, owing to increase expression and nuclear transition of its downstream protein CTSL. Conclusion: Taken together, these data reveal the role of the mut-p53/Egr-1/CTSL axis in regulating the signaling pathway responsible for IR-induced EMT. [ABSTRACT FROM AUTHOR]

Alternaria alternata is the major threat to postharvest storage of jujube (Ziziphus jujuba Mill.) fruit. We found that natural A. alternata infection can cause very typical phenotype of 'green ring' and 'red ring' surrounding the disease spot on the jujube fruit. The phenotype was successfully modeled and constructed on jujubes by artificial inoculation with the pathogen. Furthermore, the pathogenic infection is evidenced essential to the onset of the phenotype. The 'red ring' circle is proved to be pre-fixed to block the 'green ring' area as a battlefield combating the pathogen's attack. We monitored the global transcriptomic profiling of 'green ring' and 'red ring' tissues from jujubes infected with A. alternata, in comparison with the mock-inoculated fruit and the control intact fruit. Large amount of differentially expressed genes were obtained in 'green ring', followed by 'red ring'. Transcriptional alterations associated with the core and peripheral phenylpropanoid and lignin pathways, plant hormonal metabolisms were greatly influenced in the 'green ring' and 'red ring' by the A. alternata infection. The integrated analysis of transcriptomic profiling and metabolic changes revealed the differentially but delicately coordinated activation of these biological processes in the 'green ring' and 'red ring' on jujubes in defensing the fungal infection. [ABSTRACT FROM AUTHOR]

• The Weibull function was used to fit stem radius variations in cold seasons. • Stem shrinkage in Picea meyeri was greater on the forest edge after stem freeze. • The diurnal temperature range regulated the freeze-induced seasonal and diurnal variations in stem size. • Stem freeze or thaw was active when the daily minimum air temperature was around −2.5 °C. Dendrometer-derived stem radius variations (SRV) have been demonstrated as useful tools to test cold acclimation, which could reflect the tree water (ice) balance in winter and thus the frost stress. However, most previous studies focus on stem increment and water relations during growing seasons, stem radius variations in cold seasons and the underlying tree physiological information are not fully exploited, limiting our understanding of the response of mid- and high-latitudinal forests to warming winter. Hourly SRV in spruces (Picea meyeri) across an elevational transect of 700 m were observed over 6 consecutive years (2012–2017) in the present study. Elevation-specific variations in the onset of stem freeze and thaw, and the magnitude of seasonal and diurnal SRV in cold seasons were explored, and ultimately their dominant environmental factors were determined. Before stem freeze, seasonal and diurnal SRV showed linear trends with elevation, which were mainly affected by air and soil water conditions. Whereas, after stem freeze, the seasonal SRV and thus the stem dehydration was greater at the lower and upper limits of the forest belt, and the daily amplitude of freeze-thaw cycles was greater at high elevations. The diurnal air temperature range dominantly controlled the SRV on different time scales after stem freeze. Stem freeze and thaw in P. meyeri was active when the daily minimum air temperature was -2.5 °C in our study region. The onset of stem freeze and thaw advanced and delayed with elevation corresponding to a rate of 5.2 and 7.5 days/ °C when adjusted for the monitored lapse rate of 0.63 °C per 100 m, respectively. Together these findings highlight the value of high-precision variations in stem size to indicate the potential freezing stress, and trees growing at high elevations might suffer greater stress caused by frost dehydration and freeze-thaw under ongoing climate change. [ABSTRACT FROM AUTHOR]

• P.meyeri tends to increase soluble sugars and starch under low soil moisture conditions. • Needle soluble sugars were more sensitive to air temperature than other organs. • NSCs in the shoots and stems were affected by both soil moisture and atmospheric factors. • Stem soluble sugars had a different response to soil moisture and vapor pressure deficit. • Root NSC reserves may be important for P.meyeri to respond to low soil moisture. Nonstructural carbohydrate (NSC) dynamics have been suggested to be an important trait reflecting carbon balance under environmental changes. However, our understanding of NSC storage dynamics, their controls, and their responses to environmental factors remain unclear. In this study, we selected the evergreen conifer Picea meyeri at five altitudes (2040 m, 2260 m, 2440 m, 2600 m, and 2740 m a.s.l.) on Luya Mountain, North-central China. NSC concentrations in the needles, shoots, stems, and roots were measured, and the environmental variables were monitored during the growing seasons in 2018 and 2019. The results showed that the NSCs first decreased slightly and then increased gradually as altitude increased in the needles, shoots, stems, and roots. The NSC concentrations with the highest levels occurring in the needles and the lowest in the stems, whereas the shoots and roots showed intermediate concentrations. Moreover, soil moisture was the major factor influencing the dynamics of NSC storage in P. meyeri. The concentrations of soluble sugars and starch in all four organs increased with decreasing soil moisture, except for needle starch. In particular, the soluble sugars in the needles were significantly negatively correlated with air temperature, and those in the stems had a different response to soil moisture and vapor pressure deficit (VPD). Furthermore, root NSCs reserves may be important for P. meyeri to respond to low soil moisture. These findings provide new insights for understanding tree NSC allocation and the mechanism of stress resistance. [ABSTRACT FROM AUTHOR]

• The magnitude and duration of tree water deficit were combined to study drought intensity. • Larch showed less limited stem water and a greater increment rate than spruce. • Interspecific differences in annual growth declined in dry years. • Species-specific responses of stem increment to the drought intensity. The heterogeneous responses of mixed forests to climate change are integral to the promotion of the resilience and resistance of forest ecosystems, yet the hydraulic and growth sensitivity of mixed tree species to environmental drivers remain largely unexplored. In this study, stem radial variations in larch (Larix principis-rupprechtii) and spruce (Picea meyeri) were monitored using high-resolution point dendrometers over six years (2014–2019) in a mixed coniferous stand in semi-humid China. The extracted hourly tree water deficit-induced stem shrinkage (TWD) and stem radial increment (SRI) were compared between tree species and among years, and the species-specific responses of the daily maximum TWD and cumulative SRI to environmental variables were fitted by linear mixed models. Averagely, larch had a lower TWD and greater SRI rate than spruce in all six growing seasons. The interspecific differences in the TWD (length, magnitude, and intensity) were significant in dry years, while significant differences in the SRI rates were in wet years. The SRI rate of larch showed a more rapid decrease than that of spruce with increasing intensity of TWD. Furthermore, the TWD of both species was mainly regulated by vapor pressure deficit (VPD) and soil water content (SWC). The TWD of larch had a stronger and earlier response to VPD, while TWD of spruce was more affected by SWC (10 cm depth). The daily SRI of larch was more significantly related to all the measured environmental variables, indicating a more sensitive response to environmental drivers than that of spruce. We identified a shift in competitive advantage from sensitive L. principis-rupprechtii to conservative P. meyeri under extreme drought conditions, providing deep insights into species‐specific water and carbon dynamics in mixed forests. [ABSTRACT FROM AUTHOR]

Ilex cornuta Lindl. et Paxt. (Aquifoliaceae family) belongs to the Ilex genus. The leaves of this plant are used for the popular herbal tea "Ku-Ding-Cha" in China due to their health benefits for sore throat, obesity and hypertension. Our previous studies have shown that the extract of Ilex cornuta root exerts cardioprotective effects in rat models of myocardial ischaemic injury, and several new kinds of triterpenoid saponins from Ilex cornuta (TSIC) have protective effects against hydrogen peroxide (H2O2)-induced cardiomyocyte injury. The aim of this study was to clarify the underlying mechanisms by which TSIC protect against H2O2-induced cardiomyocyte injury. An H2O2-treated H9c2 cardiomyocyte line was used as an in vitro model of oxidation-damaged cardiomyocytes to evaluate the effects of TSIC. Apoptosis was detected with CCK-8 and annexin V assays and via analysis of the levels of apoptosis-associated proteins or genes. The underlying mechanisms related to Akt signalling, Ezh2 expression and activity, and ROS were clarified by Western blotting, quantitative PCR, flow cytometry and rescue experiments. TSIC protected H9c2 cells from H2O2-induced apoptosis. This effect of TSIC was attributable to inhibition of Ezh2 activity, as exhibited by attenuation of H2O2-induced Akt signalling-dependent phosphorylation of Ezh2 at serine 21 (pEzh2 S21) upon TSIC pretreatment. In addition, feedback pathway between Akt-dependent Ezh2 phosphorylation and ROS was involved in TSIC-mediated protection of H9c2 cells from apoptosis. Our findings indicate a pivotal role of the pEzh2 S21 network in TSIC-mediated protection against cardiomyocyte apoptosis, potentially providing evidence of the mechanism of TSIC in the treatment and prevention of cardiovascular diseases. Image 1 [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma (NB) is the most common pediatric solid tumor that originates from neural crest-derived sympathoadrenal precursor cells that are committed to development of sympathetic nervous system. The well differentiated histological phenotype of NB tumor cells has been reportedly associated with favorable patient outcome. Retinoic acid (RA) can effectively induce NB cell differentiation, thereby being used in the clinic as a treatment agent for inducing the differentiation of high-risk NB. However, the underlying molecular mechanisms of regulating differentiation remain elusive. Methods: The correlation between clinical characteristics, survival and the deubiquitinating enzyme ubiquitin C-terminal hydrolase 1 (UCHL1) expression were assessed using a neuroblastic tumor tissue microarray, and then validated in three independent patient datasets. The different expression of UCHL1 in ganglioneuroblastoma, ganglioneuroma and NB was detected by immunohistochemistry, mass spectra and immunoblotting analysis, and the correlation between UCHL1 expression and the differentiated histology was analyzed, which was also validated in three independent patient datasets. Furthermore, the roles of UCHL1 in NB cell differentiation and proliferation and the underlying mechanisms were studied by using short hairpin RNA and its inhibitor LDN57444 in vitro. Results: Based on our neuroblastic tumor tissue microarrays and three independent validation datasets (Oberthuer, Versteeg and Seeger), we identified that UCHL1 served as a prognostic marker for better clinical outcome in NB. We further demonstrated that high UCHL1 expression was associated with NB differentiation, indicated by higher UCHL1 expression in ganglioneuroblastomas/ganglioneuromas and well-differentiated NB than poorly differentiated NB, and the positive correlation between UCHL1 and differentiation markers. As expected, inhibiting UCHL1 by knockdown or LDN57444 could significantly inhibit RA-induced neural differentiation of NB tumor cells, characterized by decreased neurite outgrowth and neural differentiation markers. This effect of UCHL1 was associated with positively regulating RA-induced AKT and ERK1/2 signaling activation. What's more, knockdown of UCHL1 conferred resistance to RA-induced growth arrest. Conclusion: Our findings identify a pivotal role of UCHL1 in NB cell differentiation and as a prognostic marker for survival in patients with NB, potentially providing a novel therapeutic target for NB. [ABSTRACT FROM AUTHOR]

Background: The activation and expansion of bipotent liver progenitor cells (LPCs) are indispensable for liver regeneration after severe or chronic liver injury. However, the underlying molecular mechanisms regulating LPCs and LPC-mediated liver regeneration remain elusive. Methods: Hepatic brain-expressed X-linked 1 (BEX1) expression was evaluated using microarray screening, real-time polymerase chain reaction, immunoblotting and immunofluorescence. LPC activation and liver injury were studied following a choline-deficient, ethionine-supplemented (CDE) diet in wild-type (WT) and Bex1−/− mice. Proliferation, apoptosis, colony formation and hepatic differentiation were examined in LPCs from WT and Bex1−/− mice. Peroxisome proliferator-activated receptor gamma was detected in Bex1-deficient LPCs and mouse livers, and was silenced to analyse the expansion of LPCs from WT and Bex1−/− mice. Results: Hepatic BEX1 expression was increased during CDE diet-induced liver injury and was highly elevated primarily in LPCs. Bex1−/− mice fed a CDE diet displayed impaired LPC expansion and liver regeneration. Bex1 deficiency inhibited LPC proliferation and enhanced LPC apoptosis in vitro. Additionally, Bex1 deficiency inhibited the colony formation of LPCs but had no effect on their hepatic differentiation. Mechanistically, BEX1 inhibited peroxisome proliferator-activated receptor gamma to promote LPC expansion. Conclusion: Our findings indicate that BEX1 plays a pivotal role in LPC activation and expansion during liver regeneration, potentially providing novel targets for liver regeneration and chronic liver disease therapies. [ABSTRACT FROM AUTHOR]