Search

Abstract Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification.

Electromagnetic railgun attracts more and more attention due to its advantage in speed, cost, and obscurity. It is found that the rail should withstand huge mechanical and thermal shocks during the launching operation. The forms of rail failure are accompanied by gouge, grooving, transition, and arc ablation, etc. The service life of the rail has become a bottleneck restricting the development of electromagnetic railgun technology. A series of researches are carried out to solve rail failure, including analysing the failure mechanism and using various advanced rail materials. This paper provides a comprehensive review of rail materials, including material composition, preparation, microstructure, and properties. We begin from a short background of the requirement of the rail material. Then a detailed investigation of rail materials is described, and the performances of those materials are introduced. Finally, further development prospect of rail material is discussed.

Ferroptosis is a new form of programmed cell death (PCD) characterized by an excess iron accumulation and subsequent unbalanced redox states. Ferroptosis is different from the already reported PCD and has unique morphological features and biochemical processes. Ferroptosis was first elaborated by Brent R. Stockwell’s lab in 2012, in which small molecules erastin and RSL-3 induce PCD in Ras mutant cell lines. Ferroptosis involves various physiological processes and occurrence of disease and especially shows strong potential in cancer treatment. Development of small molecule compounds based on Stockwell’s research was found to kill cancer cells, and some FDA-approved drugs were discovered to result in ferroptosis of cancer cells. Radiotherapy and checkpoint therapy have been widely used as a treatment for many types of cancer. Recently, some papers have reported that chemotherapy, radiotherapy, and checkpoint therapy induce ferroptosis of cancer cells, which provides new strategies for cancer treatment. Nevertheless, the limitless proliferation of tumor cells and the lack of cell death mechanisms are important reasons for drug resistance for tumor therapy. Therefore, we reviewed the molecular mechanism of ferroptosis and sensitivity to ferroptosis of different cancer cells and tumor treatment strategy.

Affected by confined aquifer, basal inrush accidents caused by excavation are common in foundation pits, and accurate estimation of the safety thickness of the base is a big concern of engineers. In this paper, a three-dimensional failure mechanism of base inrush was constructed for a rectangular foundation pit. In this mechanism, the strength of the soil mass was assumed to be nonhomogeneous along the depth, and the soil-mass failure satisfied the linear and nonlinear Mohr–Coulomb strength criteria. Then, based on the limit equilibrium theory, the prediction method for the safety thickness of the base against confined water inrush was deduced, and a comparison with existing research works was conducted. Furthermore, the influence laws of soil strength parameters, pit design parameters, and confined water pressure on the critical safety thickness were analyzed. The results show that the critical safety thickness of the base is positively correlated with nonlinear coefficient and confined water pressure but negatively correlated with cohesion, internal friction angle, nonhomogeneity coefficient, and unit weight. The soil strength is a key factor affecting the base safety thickness, which should be paid enough attention to in engineering design and construction. The research findings in this paper can provide a theoretical reference for the prevention and control of basal inrush accidents in confined water strata.

The construction of the highly active transition-metal phosphide/carbon-based electrocatalyst from metal-organic frameworks (MOFs) precursors is considered as an efficient approach. In this work, ZIF-67/GO precursors were firstly obtained by the in situ controllable growth of ZIF-67 nanocrystals on both surfaces of GO sheets. Then, a highly efficient bifunctional electrocatalyst CoP/Co@NPC@rGO nanocomposite was derived by the thermal pyrolysis of ZIF-67/GO precursors under N2 atmosphere and a subsequent phosphatization process. The structure and elemental composition of the ZIF-67/GO, Co@NPC@rGO, and CoP/Co@NPC@rGO nanocomposites were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and N2 ad-/desorption isotherms analysis. The Co@NPC@rGO‒800 nanocomposite exhibits a high Brunauer-Emmett-Teller (BET) surface area of 186.27 m2·g‒1, indicating that both micropores and mesopores existed. Subsequently, the electrocatalytic properties of the CoP/Co@NPC@rGO nanocomposites for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) were investigated by electrochemical measurements. The results suggest that the obtained CoP/Co@NPC@rGO‒350 nanocomposite only requires an overpotential of 127 mV to reach a current density of 10 mA·cm‒2 for HER in 1.0 mol·L–1 KOH solution. For OER, CoP/Co@NPC@rGO‒350 nanocomposite can reach a current density of 10 mA·cm‒2 at an overpotential of 276 mV, with a Tafel slope of 42 mV·dec−1, in the same alkaline aqueous solution, which is superior to RuO2. In addition, for both HER and OER, CoP/Co@NPC@rGO‒350 nanocomposite also shows impressive strong durability in alkaline aqueous solution. The outstanding performance can be attributed to the synergistic effect of coupled highly graphitized N-doped porous carbon and N-doped graphene. The as-prepared CoP/Co@NPC@rGO‒350 electrocatalyst is a promising candidate for overall water splitting in the alkaline solution. This development offers an attractive catalyst material based on MOF/GO composites. It is expected that the presented strategy can be extended to the fabrication of other composites electrode materials for more efficient water splitting.

Abstract Background Ambulatory surgery maintains the advantages of a more rapid return to work and overall reduced hospital costs. The specific impact of ambulatory surgery for anal fistula using the LIFT procedure (ligation of the intersphincteric fistula tract) is presented. Methods A total of 218 consecutive patients with anal fistula who underwent ambulatory LIFT surgery were retrospectively compared with 386 cases managed as in-patients. Patient demographics, comorbidities, postoperative morbidity and pain as well as readmission rates within 30 days and satisfaction ratings were compared between the two groups. Results When compared with patients undergoing in-patient surgery, those in the ambulatory group were younger with a better level of education (P

Oral bioavailability of arsenic (As) determines levels of As exposure via ingestion of As-contaminated soil, however, the role of gut microbiota in As bioavailability has not evaluated in vivo although some in vitro studies have investigated this. Here, we made a comparison in As relative bioavailability (RBA) estimates for a contaminated soil (3913 mg As kg−1) using a mouse model with and without penicillin perturbing gut microbiota and metabolites. Compared to soil exposure alone (2% w/w soil in diets), addition of penicillin (100 or 1000 mg kg−1) reduced probiotic Lactobacillus and sulfate-reducing bacteria Desulfovibrio, enriched penicillin-resistant Enterobacter and Bacteroides, and decreased amino acid concentrations in ileum. With perturbed gut microbiota and metabolic profile, penicillin and soil co-exposed mice accumulated 2.81–3.81-fold less As in kidneys, excreted 1.02–1.35-fold less As in urine, and showed lower As-RBA (25.7–29.0%) compared to mice receiving diets amended with soil alone (56 ± 9.63%). One mechanism accounted for this is the decreased concentrations of amino acids arising from the gut microbiota shift which resulted in elevated iron (Fe) and As co-precipitation, leading to reduced As solubilization in the intestine. Another mechanism was conversion of bioavailable inorganic As to less bioavailable monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) by the antibiotic perturbed microflora. Based on in vivo mouse model, we demonstrated the important role of gut microbiota and gut metabolites in participating soil As solubilization and speciation transformation then affecting As oral bioavailability. Results are useful to better understand the role of gut bacteria in affecting As metabolism and the health risks of As-contaminated soils.

Introduction: Over the past two decades, China has experienced rapid economic development, which has not only led to a rapid increase in the use of raw materials but has also created environmental problems. This research analyzes the environmental impacts of resource extraction in China at the provincial level, and fully considers the environmental impact of various resources extraction. In addition, it is the first time to quantitatively study the spatial pattern and evolution characteristics of the environmental impacts of China’s resource extraction from multiple perspectives by means of spatial visualization. Outcomes: The results showed that the center of gravity of abiotic depletion potential (ADP) moved northwest, respiratory inorganics (RI) moved southwest and global warming potential (GWP) moved west. The results of the standard deviation ellipse showed that RI and GWP varied over time and space, while ADP showed a discrete trend. In addition, the distribution of the four in the northeast-southwest direction became more prominent. Conclusion: To mitigate the environmental impacts of resource extraction, we recommend that regional governments implement measures to control environmental impacts in the provinces within the distributed ellipse and design targeted policies based on actual conditions.

A large amount of foam is generated in the production of microbial oil and exopolysaccharide (EPS) by Sporidiobolus pararoseus JD-2, which causes low efficiency in fermentation. In this study, we aimed to reduce the negative effects of foams on the co-production of oil and EPS by controlling the formation of foams in broth. As we have found, the formation of foams is positively associated with cell growth state, air entrapment, and properties of broth. The efficient foam-control method of adding 0.03% (v/v) of the emulsified polyoxyethylene polyoxypropylene pentaerythritol ether (PPE) and feeding corn steep liquor (CSL) at 8–24 h with speed of 0.02 L/h considerably improved the fermentation performance of S. pararoseus JD-2, and significantly increased the oil and EPS concentrations by 8.7% and 12.9%, respectively. The biomass, oil, and EPS concentrations were further increased using a foam backflow device combined with adding 0.03% (v/v) of the emulsified PPE and feeding CSL at 8–24 h, which reached to 62.3 ± 1.8 g/L, 31.2 ± 0.8 g/L, and 10.9 ± 0.4 g/L, respectively. The effective strategy for controlling the formation of foams in fermentation broth reported here could be used as a technical reference for producing frothing products in fed-batch fermentation.

Background/Aims: This study was developed to investigate a potential therapeutic method for myocardial ischemia/reperfusion injury involving the promotion of miR-24-3p expression. Methods: Microarray analysis was used to screen differentially expressed genes in a myocardial ischemia/reperfusion (I/R) injury mouse model. Gene set enrichment analysis was utilized to determine vital signaling pathways. Targeting verification was conducted with a luciferase reporter assay. Myocardial I/R injury was developed in mice, and the expression levels of RIPK1 and miR-24-3p were investigated by qRT-PCR and Western blot. Hemodynamic parameters and the activity of serum myocardial enzymes were measured to evaluate cardiac function. Infarct area was observed through HE and TTC staining. Myocardial cell apoptosis was examined by TUNEL staining and caspase-3 activity analysis. Results: RIPK1 was an upregulated mRNA found by microarray analysis and a verified target of the downregulated miRNA miR-24-3p. The upregulation of RIPK1 (1.8-fold) and the downregulation of miR-24-3p (0.3-fold) were confirmed in I/R mice. RIPK1 led to impaired cardiac function indexes, increased infarct area and cell apoptosis, while miR-24-3p could reverse the injury by regulating RIPK1. The TNF signaling pathway was proven to be involved in myocardial I/R injury through the detection of the dysregulation of related proteins. Conclusion: In conclusion, RIPK1 was upregulated and miR-24-3p was downregulated in a myocardial I/R injury mouse model. RIPK1 could aggravate myocardial I/R injury via the TNF signaling pathway, while miR-24-3p could suppress RIPK1 and therefore exert cardioprotective effects in myocardial I/R injury.

Abstract Numerous irregular flow structures exist in the complicated multiphase flow and result in lots of disparate spatial dynamical flow behaviors. The vertical oil-water slug flow continually attracts plenty of research interests on account of its significant importance. Based on the spatial transient flow information acquired through our designed double-layer distributed-sector conductance sensor, we construct multilayer modality-based network to encode the intricate spatial flow behavior. Particularly, we calculate the PageRank versatility and multilayer weighted clustering coefficient to quantitatively explore the inferred multilayer modality-based networks. Our analysis allows characterizing the complicated evolution of oil-water slug flow, from the opening formation of oil slugs, to the succedent inter-collision and coalescence among oil slugs, and then to the dispersed oil bubbles. These properties render our developed method particularly powerful for mining the essential flow features from the multilayer sensor measurements.

In this paper, two low carbon microalloyed steels, named as steel A and steel B, were fabricated by ultra fast cooling (UFC). In both steels, the microstructures containing quasi polygonal ferrite (QF), acicular ferrite (AF) and granular bainite (GB) can be obtained by UFC process. The amount of AF in steel B is more than that in steel A. The size and distribution of precipitates (Nb/Ti carbonitrides) in steel B are finer and more dispersed than those of in steel A due to relatively low finish cooling temperature. The mechanical properties of both steels are effectively enhanced by UFC process. UFC process produces low-temperature transformation microstructures containing a significant amount of AF. The mechanical properties of steel B were more satisfactory than those of steel A due to the finer average grain size, the greater amount of the volume fractions and smaller size of secondary phases.

Flueggea virosa is a tropical plant of the Phyllanthaceae family, which has high medicinal value. Here, we report and characterize the complete plastome of F. virosa. The complete plastome is 154,961 bp in length and contains the typical structure and gene content of angiosperm plastome, including two inverted repeat (IR) regions of 27,575 bp, a large single-copy (LSC) region of 83,397 bp and a small single-copy (SSC) region of 16,414 bp. The plastome contains 130 genes, consisting of 80 unique protein-coding genes, 30 unique tRNA gene, 4 unique rRNA genes (5S rRNA, 4.5S rRNA, 23S rRNA and 16S rRNA). The overall A/T content in the plastome of F. virosa is 63.10%. The complete plastome sequence of F. virosa will provide a useful resource for the conservation genetics of this species as well as for phylogenetic studies in Phyllanthaceae.

Determination of the required supporting pressure is the premise of tunnel support design. Only when the support design meets the requirements can the tunnel be safe and stable during construction and operation. This paper focuses on a shallow tunnel in layered rock strata and proposes a method for predicting the required supporting pressure. In this method, the 2D and 3D failure mechanisms are constructed, respectively. The analytical solutions of the supporting pressure corresponding to the two cases are derived on the basis of upper bound theorem and Hoek–Brown failure criterion. Then, the proposed method is validated by comparing with the results of existing research studies. Furthermore, a shallow tunnel in two-layer rock strata is chosen to illustrate the difference between the two solutions. The comparison shows that the supporting pressure in the 2D case is greater than that in the 3D case in general and it tends to be conservative for tunnel design. Conversely, the 3D solution may help to reduce the support cost. Furthermore, the change laws of the supporting pressure and failure range corresponding to varying parameters are obtained. These results may practically provide theoretical references for tunnel support design in layered rock strata.

Utilization of the adaptive immune system against malignancies, both by immune-based therapies to activate T cells in vivo to attack cancer and by T-cell therapies to transfer effector cytolytic T lymphocytes (CTL) to the cancer patient, represent major novel therapeutic advancements in oncologic therapy. Allogeneic hematopoietic stem cell (HSC) transplantation (HSCT) is a form of cell-based therapy, which replaces the HSC in the patient's bone marrow but also serves as a T-cell therapy due to the Graft-vs.-leukemia (GVL) effect mediated by donor T cells transferred with the graft. Allogeneic HSCT provides one potentially curative option to patients with relapsed or refractory leukemia but Graft-vs.-Host-Disease (GVHD) is the main cause of non-relapse mortality and limits the therapeutic benefit of allogeneic HSCT. Metabolism is a common cellular feature and has a key role in the differentiation and function of T cells during the immune response. Naïve T cells and memory T cells that mediate GVHD and GVL, respectively, utilize distinct metabolic programs to obtain their immunological and functional specification. Thus, metabolic targets that mediate immunosuppression might differentially affect the functional program of GVHD-mediating or GVL-mediating T cells. Components of the innate immune system that are indispensable for the activation of alloreactive T cells are also subjected to metabolism-dependent regulation. Metabolic alterations have also been implicated in the resistance to chemotherapy and survival of malignant cells such as leukemia and lymphoma, which are targeted by GVL-mediating T cells. Development of novel approaches to inhibit the activation of GVHD-specific naïve T cell but maintain the function of GVL-specific memory T cells will have a major impact on the therapeutic benefit of HSCT. Here, we will highlight the importance of metabolism on the function of GVHD-inducing and GVL-inducing alloreactive T cells as well as on antigen presenting cells (APC), which are required for presentation of host antigens. We will also analyze the metabolic alterations involved in the leukemogenesis which could differentiate leukemia initiating cells from normal HSC, providing potential therapeutic opportunities. Finally, we will discuss the immuno-metabolic effects of key drugs that might be repurposed for metabolic management of GVHD without compromising GVL.

In this study, we propose a method for predicting the supporting pressure required for shallow tunnels in layered soils, based on a curved roof collapse mechanism with multi-failure surfaces. In this method, the effect of the number and thickness of soil layers, pore water pressure, arbitrary roof profile, and ground additional load is considered simultaneously. A nonlinear power-law failure criterion is employed to describe the failure characteristics of the roof soils. The internal energy dissipation rate and the work rates produced by external forces are obtained based on the associated flow rule and plasticity potential theory. The analytical expressions of the required supporting pressure and roof collapse surfaces are obtained with the upper bound method. Furtherly, a shallow rectangular tunnel in two soil layers is selected for parametric investigation. The change laws of the required supporting pressure and collapse curves under varying parameters are obtained. Furthermore, the corresponding engineering recommendations are given, which may potentially provide references for the support design and construction of shallow tunnels in layered strata.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare subtype of dendritic cell neoplasms, and current knowledge on this tumor is limited. We herein report a case of an IDCS in a 64-year-old man who presented with a right inguinal mass combined with extensive retroperitoneal, pulmonary, hepatic, renal, and bone marrow infiltration. Because of the advanced stage of the disease, we performed five cycles of chemotherapy, including cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); and ABVD combined with cisplatin, and one cycle of radiotherapy. The patient’s inguinal mass became smaller during the treatment, but there was no change in the extent of infiltration at the other sites. The patient died 8 months after the initial diagnosis. We also herein review the etiology, diagnosis, differential diagnosis, treatment, and prognosis of IDCS, and analyze the characteristics of IDCS in Chinese patients.

Objective(s): Salvia miltiorrhiza (SM) is a popular and classic herb in traditional Chineses medicines. The objective is to confirm the effects of aqueous extract of S. miltiorrhiza (ESM) and its main ingredient on the promotion of orthodontic tooth movement and healing of periodontal ligament in rat. Materials and Methods: Male Sprague-Dawley rats (n= 150) were divided into five groups: model control group (0.5 ml/kg phosphate-buffered saline (PBS) injection), ESM group (0.75 g/kg/day of crude drugs) and Danshensu subgroups (250, 500, 750 mg/kg/day of body weight). All rats were administered intramuscularly into the buccal vestibular mucosa of first molar of left maxillary. The indicators such as the moving distance of orthodontic tooth, nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) expression and osteoclasts were tested. Results: The expressions of RANKL and OPG in the treatment groups were obviously enhanced compared with control group (P

In the present study, two new phenolic compounds 1 and 11, a pair of lignan isomers 12 and 13 with their absolute configurations established for the first time, were isolated from the ethanol extract of the roots of Rhodiola crenulata, together with 13 known phenolic compounds, and their structures were elucidated via NMR, HRESIMS, UV, IR and CD analyses. All the isolated compounds were evaluated for their in vitro antioxidant activities using the 2,2-diphenyl-1-picryhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. Ten of them exhibited significant antioxidant activities compared to ascorbic acid. Furthermore, the inducibilities of the isolated compounds to IFN-γ production were also assessed. Compounds 1, 8, 9, 12, 13, 14 and 15 could moderately stimulate IFN-γ expression.

Strained silicon (ε-Si) is a promising material that could extend Moore’s law by enhancing electron mobility. A ε-Si material is usually composed of multiscale, multilayer heterostructures, where the strained-silicon film or strap is tens-of-nanometers thick, and its buffer layers are of the micrometer scale. The structural properties determine the electrical performance and reliability of ε-Si-based devices. Inhomogeneous residual stress is induced during the preparation, which induces ε-Si structure failure. In this work, biaxial strained-silicon films that contain graded and relaxed germanium-silicon buffer layers were prepared on monocrystalline silicon wafers through reduced-pressure chemical-vapor epitaxy. The layer components and thicknesses were measured using energy-dispersive spectroscopy and scanning-electron microscopy. Crystal and lattice characters were observed by using high-resolution transmission-electron microscopy and micro-Raman spectroscopy. The residual stress distribution along cross-sections of the ε-Si multilayer structures was examined by using micro-Raman mapping. The experimental results showed that, with a gradual increase in germanium concentration, the increasing residual stress was suppressed owing to dislocation networks and dislocation loops inside the buffer layers, which favored the practical application.

BACKGROUND: Neuraxial application of dexmedetomidine (DEX) as adjuvant analgesic has been invetigated in some randomized controlled trials (RCTs) but not been approved because of the inconsistency of efficacy and safety in these RCTs. We performed this meta-analysis to access the efficacy and safety of neuraxial DEX as local anaesthetic (LA) adjuvant. METHODS: We searched PubMed, PsycINFO, Scopus, EMBASE, and CENTRAL databases from inception to June 2013 for RCTs that investigated the analgesia efficacy and safety for neuraxial application DEX as LA adjuvant. Effects were summarized using standardized mean differences (SMDs), weighed mean differences (WMDs) or odds ratio (OR) with suitable effect model. The primary outcomes were postoperative pain intensity and analgesic duration, bradycardia and hypotension. RESULTS: Sixteen RCTs involving 1092 participants were included. Neuraxial DEX significantly decreased postoperative pain intensity (SMD, -1.29; 95% confidence interval (CI), -1.70 to -0.89; P

BACKGROUND: Embryonic Stem Cells (ESCs) can differentiate into cardiomyocytes (CMs) in vitro but the differentiation level from ESCs is low. Here we describe a simple co-culture model by commercially available Millicell™ hanging cell culture inserts to control the long-term differentiation of ESCs into CMs. METHODOLOGY/PRINCIPAL FINDINGS: Mouse ESCs were cultured in hanging drops to form embryoid bodies (EBs) and treated with 0.1 mmol/L ascorbic acid to induce the differentiation of ESCs into CMs. In the indirect co-culture system, EBs were co-cultured with epidermal keratinocytes (EKs) or neonatal CMs (NCMs) by the hanging cell culture inserts (PET membranes with 1 µm pores). The molecular expressions and functional properties of ESC-derived CMs in prolonged culture course were evaluated. During time course of ESC differentiation, the percentages of EBs with contracting areas in NCMs co-culture were significantly higher than that without co-culture or in EKs co-culture. The functional maintenance of ESC-derived CMs were more prominent in NCMs co-culture model. CONCLUSIONS/SIGNIFICANCE: These results indicate that NCMs co-culture promote ESC differentiation and has a further effect on cell growth and differentiation. We assume that the improvement of the differentiating efficiency of ESCs into CMs in the co-culture system do not result from the effect of co-culture directly on cell differentiation, but rather by signaling effects that influence the cells in proliferation and long-term function maintenance.

Cardiac hypertrophy is an independent predictor of cardiovascular morbidity and mortality. In recent years, evidences suggest that high-mobility group box 1 (HMGB1) protein, an inflammatory cytokine, participates in cardiac remodeling; however, the involvement of HMGB1 in the pathogenesis of cardiac hypertrophy remains unknown. The aim of this study was to investigate whether HMGB1 is sufficient to induce cardiomyocyte hypertrophy and to identify the possible mechanisms underlying the hypertrophic response. Cardiomyocytes isolated from 1-day-old Sprague-Dawley rats were treated with recombinant HMGB1, at concentrations ranging from 50 ng/mL to 200 ng/mL. After 24 hours, cardiomyocytes were processed for the evaluation of atrial natriuretic peptide (ANP) and calcineurin A expression. Western blot and real-time RT-PCR was used to detect protein and mRNA expression levels, respectively. The activity of calcineurin was also evaluated using a biochemical enzyme assay. HMGB1 induced cardiomyocyte hypertrophy, characterized by enhanced expression of ANP, and increased protein synthesis. Meanwhile, increased calcineurin activity and calcineurin A protein expression were observed in cardiomyocytes preconditioned with HMGB1. Furthermore, cyclosporin A pretreatment partially inhibited the HMGB1-induced cardiomyocyte hypertrophy. Our findings suggest that HMGB1 leads to cardiac hypertrophy, at least in part through activating calcineurin.