The Function of H2A Histone Variants and Their Roles in Diseases.

Epigenetic regulation, which is characterized by reversible and heritable genetic alterations without changing DNA sequences, has recently been increasingly studied in diseases. Histone variant regulation is an essential component of epigenetic regulation. The substitution of canonical histones by histone variants profoundly alters the local chromatin structure and modulates DNA accessibility to regulatory factors, thereby exerting a pivotal influence on gene regulation and DNA damage repair. Histone H2A variants, mainly including H2A.Z, H2A.B, macroH2A, and H2A.X, are the most abundant identified variants among all histone variants with the greatest sequence diversity. Harboring varied chromatin occupancy and structures, histone H2A variants perform distinct functions in gene transcription and DNA damage repair. They are implicated in multiple pathophysiological mechanisms and the emergence of different illnesses. Cancer, embryonic development abnormalities, neurological diseases, metabolic diseases, and heart diseases have all been linked to histone H2A variant alterations. This review focuses on the functions of H2A histone variants in mammals, including H2A.Z, H2A.B, macroH2A, and H2A.X, and their current roles in various diseases.

Preparation of Zn3Nb2O8 anode material for high-performance lithium/sodium-ion batteries.

Niobium-based oxides (M-Nb-O) as promising lithium/sodium-ion storage anode materials have attracted much attention. More types of niobium-based oxides are prepared in order to provide more candidates for anode materials. Herein, Zn3Nb2O8 as a novel intercalation-type anode material has been reported for the first time. Arborescent Zn3Nb2O8 particles (Zn3Nb2O8-A) and stump-like Zn3Nb2O8 particles (Zn3Nb2O8-B) have been prepared by solid-state and solvothermal methods, respectively. Benefiting from the microsized stump-like structure and the exposure of the (110) facet, Zn3Nb2O8-B delivers superior long-term cycling stability with a 139.6% capacity retention (291.8 mA h g-1) over 650 cycles at 0.5 A g-1 and a large reversible specific capacity of 91.4 mA h g-1 at 4.0 A g-1 in lithium-ion batteries. Furthermore, the Zn3Nb2O8-B electrode exhibits outstanding cycling stability (100.1 mA h g-1 with 94.5% capacity retention after 400 cycles at 0.5 A g-1) in sodium-ion batteries. The excellent electrochemical performance of the stump-like Zn3Nb2O8-B materials can be attributed to the exposure of the (110) facet, enlarged interlayer spacing, small charge transfer resistance, and high pseudocapacitive contribution. Therefore, Zn3Nb2O8-B has great application prospects as an anode material for lithium/sodium-ion storage.

CircInpp5b Ameliorates Renal Interstitial Fibrosis by Promoting the Lysosomal Degradation of DDX1.

Renal interstitial fibrosis (RIF) is a classic pathophysiological process of chronic kidney disease (CKD). However, the mechanisms underlying RIF remain unclear. The present study found that a novel circular RNA, cirInpp5b, might be involved in RIF by high-throughput sequencing. Subsequent experiments revealed that circInpp5b was reduced in UUO mouse kidney tissues and TGF-ß1-treated proximal tubular cells. The overexpression of circInpp5b inhibited RIF in UUO mice and prevented extracellular matrix (ECM) deposition in TGF-ß1-treated proximal tubular cells. Furthermore, overexpression of circInpp5b down-regulated the protein level of DDX1. Mechanistically, circInpp5b bound to the DDX1 protein and promoted its lysosomal degradation. Collectively, the findings of our study demonstrate that circInpp5b ameliorates RIF by binding to the DDX1 protein and promoting its lysosomal degradation.

Mitochondrial KATP channel-mediated autophagy contributes to angiotensin II-induced vascular dysfunction in mice.

BACKGROUND AND AIM: The present study aimed to investigate whether the mitochondrial KATP channel contributes to angiotensin II (Ang II)-induced vascular dysfunction, the development of hypertension, and atherosclerosis. METHODS AND RESULTS: ApoE (-/-) mice fed a high-fat diet were chronically infused with Ang II for eight weeks and concomitantly treated with losartan (ARB), apocynin, or 5-hydroxy decanoate (5-HD), or 3-methyladenine (3-MA). Systolic blood pressure was measured, and pathological changes of aortic or liver tissue were observed. Nitric oxide (NO), superoxide dismutase 2 (SOD2) levels and vasorelaxation rate were measured, and protein and mRNA expressions were examined by western blot and RT-PCR. Ang II-induced development of hypertension was suppressed not only by ARB, and apocynin but also by 5-HD or 3-MA. Ang II infusion decreased aortic NO production and relaxation, as well as SOD2 activity in liver, which were improved by all treatments. In addition, Ang II-induced activation of autophagy was suppressed by 5-HD in aortic tissue, furthermore, Ang II increases the atherosclerotic index in plasma and exacerbates the development of atherosclerosis by increases of fat deposition in the aorta and liver. Lipid metabolism-related mRNA expressions (LXR-α, LDLR, SRBI, Acca, and FASN) were changed by Ang II. Similarly, not only ARB, and apocynin, but also 5-HD and 3-MA suppressed Ang II-induced these changes. CONCLUSIONS: Our present findings evidence that mitochondrial KATP channel-mediated autophagy contributes to Ang II-induced vascular dysfunction, development of hypertension, and atherosclerosis.

A novel APC mutation associated with Gardner syndrome in a Chinese family.

Gardner syndrome (GS) is a specific form of familial adenomatous polyposis (FAP), which manifests as colorectal polyps, multiple osteomas and soft tissue tumors, and in the oral cavity as osteomas of the jaws, odontomas, and abnormal tooth counts. The underlying cause of GS is attributed to mutations in the APC gene. Mutations in this gene disrupt the normal functioning of the protein and lead to the development of GS. To further investigate GS, a family affected by the syndrome was selected from Dongguan, Guangdong Province. The family members underwent a comprehensive survey, which involved collecting clinical data and peripheral venous blood samples. The samples were then used for genetic analysis. Whole exome sequencing (WES) and Sanger sequencing techniques were utilized to screen and identify specific mutation sites in the APC gene. The clinical findings for the GS family included the presence of gastrointestinal polyps and odontomas. After analyzing the genetic sequencing results, a novel mutation site c.4266dupA on the APC gene was found in the patients, which leading to the APC protein truncation. As a result of this study, it is suggested that odontoma may be an early indicator of GS. Additionally, the identification of this novel mutation site in the APC gene expands the known spectrum of genetic mutations associated with the disease. This discovery has significant implications for the early diagnosis of GS, thus enabling timely intervention to reduce the risk of developing colon cancer and other related diseases.

Chemically bonding inorganic fillers with polymer to achieve ultra-stable solid-state sodium batteries.

Inorganic/organic composite solid electrolytes (CSEs) have attracted ever-increasing attentions due to their outstanding mechanical stability and processibility. However, the inferior inorganic/organic interface compatibility limits their ionic conductivity and electrochemical stability, which hinders their application in solid-state batteries. Herein, we report a homogeneously distributed inorganic fillers in polymer by in-situ anchoring SiO2 particles in polyethylene oxide (PEO) matrix (I-PEO-SiO2). Compared with ex-situ CSEs (E-PEO-SiO2), SiO2 particles and PEO chains in I-PEO-SiO2 CSEs are closely welded by strong chemical bonds, thus addressing the issue of interfacial compatibility and realizing excellent dendrite-suppression ability. In addition, the Lewis acid-base interactions between SiO2 and salts facilitate the dissociation of sodium salts and increase the concentration of free Na+. Consequently, the I-PEO-SiO2 electrolyte demonstrates an improved Na+ conductivity (2.3 × 10-4 S cm-1 at 60 °C) and Na+ transference number (0.46). The as constructed Na3V2(PO4)3 ‖ I-PEO-SiO2 ‖ Na full-cell demonstrates a high specific capacity of 90.5 mAh g-1 at 3C and an ultra-long cycling stability (>4000 cycles at 1C), outperforming the state-of-the-art literatures. This work provides an effective way to solve the issue of interfacial compatibility, which can enlighten other CSEs to overcome their interior compatibility.

Characterization of a retromolar foramen in a Chinese population: A radiographic study.

BACKGROUND: Retromolar canal (RMC) arises from the mandibular canal (MC) behind the second or third molar and travels anterosuperiorly to a retromolar foramen (RMF). RMCs and RMFs have generally been ignored in anatomical textbooks and have rarely been reviewed or studied in the anatomical and dental literature until the last decades. OBJECTIVE: This study aimed to characterize RMF in a Chinese population concerning its incidence, origin, and classification via anatomical study and periapical radiography. METHODS: 123 dry adult Chinese mandibles were collected to observe the incidence of RMFs. RMFs were determined using a steel wire 0.5 mm in diameter. The passways or origins of the retromolar canal (RMC) were determined and classified via periapical radiography. For each RMF, two dentists independently measured the diameter and its distances to the lingual cortex, the buccal cortex, and the distal edge of the last tooth (or the alveolar fossa) using a vernier caliper. RESULTS: The incidence of RMFs was 31.71%. The average RMF diameter was 0.78 ± 0.27 mm. From RMF, the distance was 4.27 ± 1.87 mm to the lingual cortex, 8.61 ± 2.23 mm to the buccal cortex, and 7.84 ± 3.87 mm to the distal edge of the last tooth (or the alveolar fossa). RMCs were classified into MC type originating from the mandibular canal and AF type originating from the alveolar fossa. The diameters of MC ones were more significant than those of AF ones. There was no apparent correlation between the existence of the third molar and the presence of an RMF. CONCLUSION: The incidence of RMFs in Chinese may be about one-third, which is a potential factor in the onset of surgery accidents. RMCs can be classified into two types by their origins. One of them is MC, which originates from the mandibular canal, and the other is AF, which originates from the alveolar fossa.

Co Nanoparticles Embedded in Mesoporous Walls of Carbon Nanoboxes for Rechargeable Zinc-air Batteries.

Design of non-noble metal electrocatalysts with high catalytic activity and stability to replace commercial Pt/C is crucial in the commercialization development of Zn-air batteries (ZABs). In this work, Co catalyst nanoparticles coupled with nitrogen-doped hollow carbon nanoboxes were well designed through zeolite-imidazole framework (ZIF-67) carbonization. As a result, the 3D hollow nanoboxes reduced the charge transport resistance, and the Co nanoparticles loaded on nitrogen-doped carbon supports exhibited excellent electrocatalytic performance for oxygen reduction reaction (ORR, E1/2 =0.823 V vs. RHE), similar to that of commercial Pt/C. Moreover, the designed catalysts showed an excellent peak density of 142 mW cm-2 when applied on ZABs. This work provides a promising strategy for the rational design of non-noble electrocatalysts with high performance for ZABs and fuel cells.

In-Plane BO3 Configuration in P2 Layered Oxide Enables Outstanding Long Cycle Performance for Sodium Ion Batteries.

P2-phase layered cathode materials with distinguished electrochemical performance for sodium-ion batteries have attracted extensive attention, but they face critical challenges of transition metal layer sliding and unfavorable formation of hydration phase upon cycling, thus showing inferior long cycle life. Herein, a new approach is reported to modulate the local structure of P2 material by constructing a state-of-the-art in-plane BO3 triangle configuration ((Na0.67 Ni0.3 Co0.1 Mn0.6 O1.94 (BO3 )0.02 ). Both are unveiled experimentally and theoretically that such a structure can serve as a robust pillar to hold up the entire structure, by inhibiting the H2 O insertion upon Na (de)intercalation and preventing the structure from deformation, which significantly boost the long cycle capability of P2-materials. Meanwhile, more Na ions in the architecture are enabled to site on the edge sharing octahedrons (Nae ), thus benefiting the Na+ transportation. Consequently, the as produced material demonstrates an ultralow volume variation (1.8%), and an outstanding capacity retention of 80.1% after 1000 cycles at 2 C. This work sheds light on efficient architecture modulation of layered oxides through proper nonmetallic element doping.

Global regulatory factor AaLaeA upregulates the production of antitumor substances in the endophytic fungus Alternaria alstroemeria.

The global regulatory factor LaeA has been shown to be involved in the biosynthesis of secondary metabolites in various fungi. In a previous work, we isolated an endophytic fungus from Artemisia annua, and its extract had a significant inhibitory effect on the A549 cancer cell line. Phylogenetic analysis further identified the strain as Alternaria alstroemeria. Overexpression of AalaeA gene resulted in significantly increased antitumor activity of this strain's extract. The 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay results showed that the inhibition rate of the AalaeAOE29 mutant extract on A549 cancer cells was significantly higher than that of the WT extract, as the IC50 decreased from 195.0 to 107.4 µg/ml, and the total apoptosis rate was enhanced. Overexpression of the AalaeA gene significantly increased the contents of myricetin, geraniol, ergosterol, and 18 other antitumor compounds as determined by metabolomic analysis. Transcriptomic analysis revealed significant changes in 95 genes in the mutant strain, including polyketide synthases, nonribosomal peptide synthases, cytochrome P450s, glycosyltransferases, acetyl-CoA acetyltransferases, and others. These results suggested that AaLaeA mediated the antitumor activity of the metabolites in A. alstroemeria by regulating multiple metabolic pathways.

Global regulatory factor VeA upregulates the production of antitumor substances in endophytic Fusarium solani.

A number of studies have demonstrated that endophytic fungi have the potential to produce antitumor active substances with novel structures and significant activities. In our previous studies, we isolated a Fusarium strain from the stem of the medicinal plant Nothapodytes pittosporoides (Oliv.). In this study, we identified this strain as Fusarium solani and found that its crude extract has significant antitumor activity against human alveolar adenocarcinoma cells (A549). We overexpressed the global regulatory factor VeA in F. solani (VeAOE), resulting in a significant increase in antitumor activity. The MTT assay results showed that the inhibition rate of the VeAOE mutant extract on A549 cancer cells was significantly higher than that of the WT extract, as the IC50 decreased from 369.22 to 285.89 µg/mL, and the apoptosis ratio was significantly increased by approximately 4.86-fold. In VeAOE, accumulation of alkaloids, terpenoids, carboxylic acid derivatives, phenols and flavonoid metabolites with potential antitumor activity was significantly increased compared with WT based on metabolomic analysis. Additionally, transcriptome analysis found that the expression patterns of 48 genes related to antitumor activity were significantly changed in VeAOE, mainly involving glycosyl hydrolases, the Zn(2)-Cys(6) class, cytochrome P450 monooxygenase, 3-isopropylmalate dehydratase, and polyketide synthases. These results suggested that VeA mediated the antitumor activity of the metabolites in F. solani HB1-J1 by regulating multiple metabolic pathways.

Overexpression of the global regulator FnVeA upregulates antitumor substances in endophytic Fusarium nematophilum.

The special niche of endophytic fungi promotes their potential to produce antitumor compounds with novel structure and significant bioactivity for screening of new antitumor drugs. In our previous studies, we isolated a Fusarium strain from the roots of the medicinal plant Nothapodytes pittosporoides and identified it as Fusarium nematophilum. We found that the crude extract of F. nematophilum had significant antitumor activity on A549 cancer cells, and overexpressing the global regulatory factor FnVeA (the VeA gene of the fungus F. nematophilum) resulted in a significant increase in the antitumor activity, which was approximately fivefold higher than wild strain for relative inhibition rate. In FnVeAOE, the accumulation of indole, alkene, alkaloid, steroid, and flavonoid metabolites with potential antitumor activity was significantly upregulated compared with wild type via metabolomic analysis. Moreover, the transcriptome analysis showed that 134 differential genes were considered to be closely related to the biosynthesis of antitumor substances, of which 59 differential genes were considered as candidate key genes, and related to tryptophan dimethylallyltransferase, cytochrome P450 monooxygenase, polyketide synthases, and transcription factors. Taken together, we suggest that FnVeA may regulate the biosynthesis of antitumor substances by mediating the expression of genes related to secondary metabolic pathways in F. nematophilum.

Facile Synthesis of SnNb2 O6 @C Composite with Ultrathin Carbon Layer as Anode Materials for High-Performance Sodium-Ion Batteries.

Niobium-based oxides have attracted a lot of attention as anode materials for sodium-ion batteries (SIBs) due to their high theoretical specific capacity, excellent rate capability and exceptional safety. However, their poor intrinsic electronic conductivity and sluggish sodium ions diffusion kinetics severely hinder their practical applicability. Here, SnNb2 O6 @C was successfully prepared by a simple solid-state reaction technique coupled with carbon coating. HRTEM images show that the SnNb2 O6 @C particles are covered with uniformly ultrathin amorphous carbon layer of about 1.8 nm, thus improving the electronic conductivity and diffusion coefficient of sodium ions. As anode for SIBs, the as-obtained SnNb2 O6 @C material exhibits excellent specific capacity (369 mAh g-1 at a current density of 50 mA g-1 ) and remarkable rate performance (177 mAh g-1 at 1000 mA g-1 ), which indicates its good prospect in practical application.

Establishment of a Convenient System for the Culture and Study of Perineurium Barrier In Vitro.

The perineurium serves as a selective, metabolically active diffusion barrier in the peripheral nervous system, which is composed of perineurial cells joined together by tight junctions (TJs). Not only are these junctions known to play an essential role in maintaining cellular polarity and tissue integrity, but also limit the paracellular diffusion of certain molecules and ions, whereas loss of TJs barrier function is imperative for tumour growth, invasion and metastasis. Hence, a detailed study on the barrier function of perineurial cells may provide insights into the molecular mechanism of perineural invasion (PNI). In this study, we aimed to develop an efficient procedure for the establishment of perineurial cell lines as a tool for investigating the physiology and pathophysiology of the peripheral nerve barriers. Herein, the isolation, expansion, characterization and maintenance of perineurial cell lines under favourable conditions are presented. Furthermore, the analysis of the phenotypic features of these perineurial cells as well as the barrier function for the study of PNI are described. Such techniques may provide a valuable means for the functional and molecular investigation of perineurial cells, and in particular may elucidate the pathogenesis and progression of PNI, and other peripheral nerve disorders.

Epitaxial Grown Carbon Nanotubes Reinforced Pyrocarbon Matrix in C/C Composites with Improved Mechanical Properties.

In order to achieve the highly efficient preparation of high-performance carbon/carbon (C/C) composites, epitaxial grown carbon nanotubes (CNTs) and a pyrocarbon matrix were simultaneously synthesized to fabricate CNT-reinforced C/C composites (CC/C composites). With precise control of the temperature gradient, CNTs and the pyrocarbon matrix could grow synchronously within a 2D needle-punched carbon fiber preform. Surprisingly, the CNTs remained intact within the pyrocarbon matrix at the nano-level, and the CNT-reinforced nano-pyrocarbon matrix was compact, with virtually no gaps and pores, which were tightly connected with the carbon fibers without cracks. Based on the results of Raman analysis, there is less residual stress in the CNT-reinforced pyrocarbon matrix and carbon fibers, and less of a mismatch between the coefficient and thermal expansion. Additionally, CC/C composites fabricated by this method could achieve a low density, open porosity with a large size, and improved mechanical properties. More importantly, our work provides a rational design strategy for the highly efficient preparation and structural design of high-performance CNT-einforced C/C composites.

Targeted Therapeutic Strategies for Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, which is characterized by the absence of estrogen receptor (ER) and progesterone receptor (PR) expression and the absence of human epidermal growth factor receptor 2 (HER2) expression/amplification. Conventional chemotherapy is the mainstay of systemic treatment for TNBC. However, lack of molecular targeted therapies and poor prognosis of TNBC patients have prompted a great effort to discover effective targets for improving the clinical outcomes. For now, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi's) and immune checkpoint inhibitors have been approved for the treatment of TNBC. Moreover, agents that target signal transduction, angiogenesis, epigenetic modifications, and cell cycle are under active preclinical or clinical investigations. In this review, we highlight the current major developments in targeted therapies of TNBC, with some descriptions about their (dis)advantages and future perspectives.

All Si3 N4 Nanowires Membrane Based High-Performance Flexible Solid-State Asymmetric Supercapacitor.

Recently, much attention has been drawn in the development of flexible energy storage devices due to the increasing demands for flexible/portable electronic devices with high energy density, low weight, and good flexibility. Herein, vertically oriented graphene nanosheets (VGNs) are in situ fabricated on the surface of free-standing and flexible Si3 N4 nanowires (NWs) membrane by plasma-enhanced chemical vapor deposition (PECVD), which are directly used as flexible nanoscale conductive substrates. NiCo2 O4 hollow nanospheres (HSs) and FeOOH amorphous nanorods (NRs) are finally prepared on Si3 N4NWs @VGNs, which are served as the positive and negative electrodes, respectively. Profiting from the structural merits, the synthesized Si3 N4NWs @VGNs@NiCo2 O4HSs and Si3 N4NWs @VGNs@FeOOHNRs membrane electrodes exhibit remarkable electrochemical performance. Using Si3 N4NWs membrane as the separator, the assembled all Si3 N4NWs membrane-based flexible solid-state asymmetric supercapacitor (ASC) with a wide operating potential window of 1.8 V yields the outstanding energy density of 96.3 Wh kg-1 , excellent cycling performance (91.7% after 6000 cycles), and good mechanical flexibility. More importantly, this work provides a rational design strategy for the preparation of flexible electrode materials and broadens the applications of Si3 N4NWs in the field of energy storage.

Hierarchical self-supporting sugar gourd-shape MOF-derived NiCo2O4 hollow nanocages@SiC nanowires for high-performance flexible hybrid supercapacitors.

Rational construction of hierarchical electrode materials has been a research hotspot in the field of energy storage. In this work, metal-organic framework (MOF) derived hollow NiCo2O4 nanocages (NCs) were strung by interwoven SiC nanowires (NWs) network on carbon cloth (CC), forming a unique sugar gourd-like core-shell architecture, which were fabricated via a multi-step process containing of chemical vapor deposition, solution reaction of MOF templates, ion exchanging/etching and subsequent heat treatment. Benefiting from the unique structural advantages, such as hierarchical porous structure with abundant active sites for electrochemical reactions and interwoven conductive networks for electron transport, the formed core-shelled CC/SiCNWs@NiCo2O4NCs as a binder supercapacitor electrode exhibits excellent electrochemical performance with a large specific capacitance (1377.6F g-1 at a current density of 1 A g-1), good rate capability (68.8% capacitance retention at 20 A g-1) and excellent cycling stability (88.3% capacitance retention after 6000 cycles). Furthermore, the hybrid supercapacitor based on CC/SiCNWs@NiCo2O4NCs and activated carbon, not only delivers a high energy density of 46.58 Wh kg-1 at the power density of 800 W kg-1, but also possesses good flexibility with high capacitance retention, exhibiting the application potential in the field of flexible energy storage. More importantly, our work gives a new thinking for structural design of SiCNWs-based and MOF-based electrode materials for high-performance flexible energy storage.

Perineural Invasion in Adenoid Cystic Carcinoma of the Salivary Glands: Where We Are and Where We Need to Go.

Adenoid cystic carcinoma of the salivary gland (SACC) is a rare malignant tumors of the head and neck region, but it is one of the most common malignant tumors that are prone to perineural invasion (PNI) of the head and neck. The prognosis of patients with SACC is strongly associated with the presence of perineural spread (PNS). Although many contributing factors have been reported, the mechanisms underlying the preferential destruction of the blood-nerve barrier (BNB) by tumors and the infiltration of the tumor microenvironment by nerve fibers in SACC, have received little research attention. This review summarizes the current knowledge concerning the characteristics of SACC in relation to the PNI, and then highlights the interplay between components of the tumor microenvironment and perineural niche, as well as their contributions to the PNI. Finally, we provide new insights into the possible mechanisms underlying the pathogenesis of PNI, with particular emphasis on the role of extracellular vesicles that may serve as an attractive entry point in future studies.

Regulatory T-cell expansion in oral and maxillofacial Langerhans cell histiocytosis.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid-origin neoplasm characterized by the expansion and dissemination of CD1 a+/CD207+ dendritic cells (LCH cells), but the rarity of its occurrence has long impeded progress in understanding its pathology. We focus on the potentially important role that regulatory T cells (T-reg) play in the oral and maxillofacial LCH tumor microenvironment (TME). STUDY DESIGN: Nine cases of oral and maxillofacial LCH, diagnosed from 2009 to 2019, were collected retrospectively from the affiliated hospitals of Southern Medical University. Immunohistochemistry was conducted characterizing T cells and T-reg phenotype. Data were evaluated by 1-sample Wilcoxon's test. RESULTS: Significantly increased frequency and abnormal distributions of T-reg were identified in all the LCH lesion sections. Proliferating T-reg account for a mean average of 11.5% of the total T-cell subsets, with significant difference (Wilcoxon's test; P < .05). CONCLUSIONS: T-reg expansion in the localized inflammatory TME leads to a failure of immune regulation by suppressing antitumor response, which can be a latent and significant factor contributing to LCH progression. However, T-reg may also acquire the capability for aiding in initiating T-cell responses under the "cytokine storm" at the beginning of LCH onset. T-reg might contribute to the augmentation of tissue repair by transforming growth factor-ß (TGF-ß), explaining the self-limiting character of LCH.