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Thyroid gland histology. Thymus gland

Thymus , or thymus gland The central organ of lymphopoiesis and immune defense.

Development . The source of development of the thymus is the multilayered epithelium lining the III and partially IV pairs of gill pouches.

Research by Sh. D. Galustyan (1949) showed that culturing the thymic epithelium leads to the formation of a structure similar to the epidermis. In the superficial cells of Hassall's bodies, an antigen characteristic of the cells of the basal layer of the epidermis was found, and in the deeper cells of the stratified bodies, antigens expressed by the cells of the spinous, granular and stratum corneum of the epidermis were found. The epithelium in the form of paired strands surrounded by mesenchyme descends along the trachea. Subsequently, both strands form a single organ.

A capsule is formed from the mesenchyme, from which connective tissue cords with blood vessels grow into the epithelial anlage and divide it into lobules. Consequently, the thymic stroma is formed by connective tissue. The stroma of its lobules is epithelial tissue, into which from the yolk sac, and later from the liver and red bone marrow CCMs migrate. Under the influence of the thymic microenvironment, they differentiate into T-lymphocytes, which together form the parenchyma of the organ.

Structure . On histological sections, the thymus appears in the form of lobules separated by connective tissue layers. The lobules consist of medulla and cortex. The stroma of the lobules is represented by epithelial cells - epithelioreticulocytes, among which there are: 1) border cells of the subcapsular zone (flat with processes); 2) non-secretory supporting cells of the deep cortex (stellate); 3) secretory cells brain matter; 4) cells of Hassal's bodies

Epithelial cells located on the periphery of the lobules are separated from the connective tissue layers by the basement membrane. They are quite closely adjacent to each other and are connected to each other by desmosomes, and to the basement membrane by hemidesmosomes.

Borderline epithelioreticulocytes of the subcapsular zone have numerous processes and intussusceptions, in which, as in a cradle, up to 20 lymphocytes are located, therefore these cells are called “nanny” cells, or “feeders”.

Non-secretory supporting epithelioreticulocytes The cortical substance of the lobules, in contact with each other with their processes, form a kind of skeleton, in the loops of which there are numerous lymphocytes. The plasmalemma of these cells contains on its surface the major histocompatibility complex, interacting with which, lymphocytes acquire the ability to recognize “their” markers, which underlies the intercellular interactions of immunocompetent cells and their reading of antigenic information.

Secretory cells The medulla in the cytoplasm contains hormone-like biologically active substances: α-thymosin, thymulin and thymopoietins, under the influence of which antigen-independent proliferation of lymphocytes occurs and their transformation into immunocompetent T-lymphocytes.

Hassall's body cells located in the medulla in the form of layers with keratinization elements.

Epithelioreticulocytes thus represent a unique microenvironment for T-lymphocytes formed in the thymus. In addition, supporting cells include macrophages and interdigitating cells (of monocyte origin), dendritic and myoid cells, as well as neuroendocrine cells that originate from the neural crest.

The most active proliferation of T-lymphocytes occurs in the cortex of the thymus lobules, while in the medulla there are significantly fewer of them and they represent predominantly a recirculating pool (“homing” - home).

It has been established that young, actively proliferating cells of the skin epithelium and its derivatives contain a thymic hormonal factor that activates the differentiation of T-lymphocytes.

Nutrient and biological intake active substances to the cells of the microenvironment and the T-lymphoblastic differon of the cortical substance of the thymus lobules is carried out diffusely from the side blood vessels, located in the connective tissue layers between the lobules. Leukocytes of the thymic cortex are separated from the blood by the hematothymic barrier, which protects them from excess antigens. Despite this, here, as in KKM, selection of T-lymphocytes is carried out, as a result of which a significant part of them (up to 95%) dies and only about 5% of the cells migrate into the bloodstream and populate the thymus-dependent zones of peripheral hematopoietic organs: lymph nodes, spleen And lymphatic formations, associated with the intestinal mucous membranes. In this case, only those lymphocytes that have been “trained” in the thymus and acquired specific receptors for antigens can migrate into the bloodstream. The same lymphocytes that have receptors for their own antigens undergo apoptosis. There is no barrier in the medulla around the blood capillaries. Postcapillary venules here are lined with high prismatic endothelium, through which lymphocytes recirculate.

With age, the thymus undergoes involutive processes (age-related involution), but this can be observed at any stage of its development under the influence of intoxication, irradiation, starvation, severe injuries, etc. stress influences(accidental involution). There is an assumption that killer, suppressor and helper T-lymphocytes are formed from independent precursors.

Thymus(thymus gland) - the organ of human lymphopoiesis, in which maturation, differentiation and immunological “training” of T cells occur immune system.

The thymus gland is a small organ of pinkish-gray color, soft consistency, its surface is lobular.

In newborns, its dimensions are on average 5 cm in length, 4 cm in width and 6 mm in thickness, and weighs about 15 grams. The growth of the organ continues until the onset of puberty (at this time its size is maximum - up to 7.5-16 cm in length, and its weight reaches 20-37 grams).

With age, the thymus undergoes atrophy and old age barely distinguishable from the surrounding fatty tissue of the mediastinum; at 75 years of age, the average weight of the thymus is only 6 grams.

As it involutions, it loses White color and due to an increase in the proportion of stroma and fat cells in it, it becomes more yellow.

Location

The thymus is located at the top chest, just behind the sternum (superior mediastinum). In front of it are adjacent the manubrium and the body of the sternum to the level of the IV costal cartilage; behind - top part pericardium, covering the initial parts of the aorta and pulmonary trunk, aortic arch, left brachiocephalic vein; on the sides - mediastinal pleura.

Separate groups of thymus lobules are found around or in the thickness of the tissue thyroid gland, V soft tissues neck, in the area of ​​the tonsils, in the fatty tissue of the anterior, less commonly, posterior mediastinum. The frequency of detection of aberrant thymus reaches 25%.

Such anomalies are more often observed in women, mainly on the left side of the neck and mediastinum. In the literature there are isolated reports of ectopic thymus tissue in children infancy. This pathology was accompanied by shortness of breath, dysphagia, and respiratory failure.

Structure

In humans, the thymus consists of two lobes, which can be fused or simply fit tightly together. Bottom part each lobe is wide, and the upper one is narrow. Thus, the upper pole may resemble a two-pronged fork (hence the name).

The organ is covered with a capsule made of dense connective tissue, from which jumpers extend into the depths, dividing it into segments.

Blood supply, lymphatic drainage and innervation

The blood supply to the thymus comes from the thymic, or thymic branches of the internal mammary artery, the thymic branches of the aortic arch and brachiocephalic trunk, and the branches of the superior and inferior thyroid arteries. Venous outflow is carried out through the branches of the internal thoracic and brachiocephalic veins.

Lymph from the organ flows into the tracheobronchial and parasternal lymph nodes.

The thymus gland is innervated by the branches of the right and left vagus nerves, as well as sympathetic nerves originating from the superior thoracic and stellate ganglia of the sympathetic trunk, located in the nerve plexuses that surround the vessels supplying the organ.

Histology

The stroma of the thymus is of epithelial origin, originating from the epithelium of the anterior part of the primary intestine. Two cords (diverticula) originate from the third branchial arch and grow into anterior mediastinum. Sometimes the thymic stroma is also formed by additional cords from the fourth pair of gill arches.

Lymphocytes originate from blood stem cells that migrate to the thymus from the liver to early stages intrauterine development. Initially, proliferation of various blood cells occurs in the thymus tissue, but soon its function is reduced to the formation of T-lymphocytes.

The thymus gland has a lobular structure; the tissue of the lobules is divided into the cortex and medulla. The cortical substance is located on the periphery of the lobule and in a histological microslide looks dark (it contains many lymphocytes - cells with large nuclei). The cortex contains arterioles and blood capillaries having a blood-thymic barrier that prevents the introduction of antigens from the blood.

The cortex contains cells:

  • epithelial origin:
  • supporting cells: form the “framework” of the tissue, form the blood-thymus barrier;
  • stellate cells: secrete soluble thymic (or thymic) hormones - thymopoietin, thymosin and others, regulating the processes of growth, maturation and differentiation of T cells and functional activity mature cells immune system.
  • “nanny” cells: have invaginations in which lymphocytes develop;
  • hematopoietic cells:
  • lymphoid series: maturing T-lymphocytes;
  • macrophage series: typical macrophages, dendritic and interdigitating cells.

Directly under the capsule, dividing T-lymphoblasts predominate in the cellular composition. Deeper are the maturing T-lymphocytes, which gradually migrate to the medulla. The ripening process takes approximately 20 days. During their maturation, genes are rearranged and the gene encoding TCR (T-cell receptor) is formed.

Next, they undergo positive selection: in interaction with epithelial cells“functionally fit” lymphocytes that are able to interact with HLA are selected; During development, the lymphocyte differentiates into a helper or killer, that is, either CD4 or CD8 remains on its surface.

Next, in contact with stromal epithelial cells, cells capable of functional interaction are selected: CD8+ lymphocytes capable of receiving HLA I, and CD4+ lymphocytes capable of receiving HLA II.

The next stage - negative selection of lymphocytes - occurs at the border with the medulla. Dendritic and interdigitating cells - cells of monocyte origin - select lymphocytes capable of interacting with antigens of their own body and trigger their apoptosis.

The medulla mainly contains maturing T-lymphocytes. From here they migrate into the bloodstream of venules with high endothelium and disperse throughout the body. The presence of mature recirculating T-lymphocytes is also assumed here.

The cellular composition of the medulla is represented by supporting epithelial cells, stellate cells, and macrophages. There are also outgoing lymphatic vessels and Hassal's bodies.

Functions

The main role of the thymus is the differentiation and cloning of T lymphocytes. In the thymus, T lymphocytes undergo selection, resulting in the release of cells into the bloodstream and tissues that can be involved in the immune response against certain foreign antigens, but not against the body's own.

Produces hormones: thymosin, thymulin, thymopoietin, insulin-like growth factor-1 (IGF-1), thymic humoral factor - all of them are proteins (polypeptides). With hypofunction of the thymus, immunity decreases, as the number of T-lymphocytes in the blood decreases.

Development

The size of the thymus is maximum in childhood, but after the onset of puberty the thymus undergoes significant atrophy and involution. An additional decrease in the size of the thymus occurs with aging of the body, which is partly associated with a decrease in immunity in older people.

Regulation

The secretion of thymic hormones and the function of the thymus is regulated by glucocorticoids - hormones of the adrenal cortex, as well as soluble immune factors - interferons, lymphokines, interleukins, which are produced by other cells of the immune system.

Glucocorticoids suppress the immune system, as well as many functions of the thymus, and lead to its atrophy.Pineal peptides slow down the involution of the thymus. Her hormone melatonin acts in a similar way, which can even cause “rejuvenation” of the organ.

Thymus diseases

  • MEDAC syndrome
  • DiGeorge syndrome
  • Myasthenia gravis can be an independent disease, but is often associated with thymoma.

Tumors

  • Thymoma - from epithelial cells of the thymus gland
  • T-cell lymphoma - from lymphocytes and their precursors
  • Pre-T-lymphoblastic tumors in some cases have a primary localization in the thymus and are detected as a massive infiltrate in the mediastinum, followed by rapid transformation into leukemia.
  • neuroendocrine tumors
  • rarer tumors (vascular and nervous origin)

Thymus tumors may be a manifestation of multiple endocrine neoplasia syndrome type I.


One of the most mysterious endocrine glands is the thymus, or thymus.

Its importance is not inferior to many others, but it has not been studied well enough.

The formation of the thymus gland occurs in the sixth week of intrauterine development. After birth, throughout childhood and adolescence, the thymus grows and increases in size.

In adults, the structure of the thymus changes, the growth rate slows down, and the glandular tissue is gradually replaced by fat cells, almost completely atrophying by the end of life. The thymus is the leading organ of the immune system, its functions are described below.

The thymus gland gets its name from characteristic appearance, resembling a two-pronged fork.

It is a small lobulated pinkish organ adjacent to the trachea.

The upper part is thinner and the lower part is wider. On the radiograph, the image of the thymus is partially covered by the shadow of the heart.

The size of the gland varies depending on age; in children they are approximately five by four centimeters. An increase (thymomegaly) can be observed when exposed to adverse factors (alcohol, nicotine, medications, etc.) both in utero and after birth.

Changes in the size of the thymus can result from:

  • Rhesus conflict, or hemolytic disease newborns;
  • asphyxia during childbirth;
  • prematurity;
  • frequent and prolonged infectious diseases;
  • tumors;
  • rickets and nutritional disorders;
  • surgical interventions.

Infants with thymomegaly require close monitoring by a pediatrician due to high risk sudden death syndrome.

Thymus gland: location in the human body

The thymus is located almost in the center of the chest, with its anterior surface adjacent to the sternum, and with its elongated upper ends reaching the thyroid gland.

In children, the lower edge reaches 3-4 ribs and is located close to the pericardium; in adults, due to a decrease in size, it is located in the second intercostal space.

Thymolipoma

Large vessels pass behind the thymus. The location of the gland is examined using a chest x-ray, ultrasound scan or magnetic resonance imaging.

Organ structure

The right and left lobes of the thymus are connected to each other by a connective tissue layer, but can be fused quite tightly. The thymus is covered on top by a dense fibrous capsule, from which cords (septal septa) of connective tissue pass into the body of the gland.

With their help, the parenchyma of the gland is divided into small incomplete lobules with cortical and medulla layers.

Structure of the thymus

Lymphatic drainage, blood supply and innervation

Despite its direct relationship to lymphatic system body, the thymus gland has features of blood supply and lymph drainage. This organ does not have afferent lymphatic vessels and does not filter lymph, unlike the mediastinal lymph nodes.

Lymphatic drainage occurs through a few capillaries originating in the wall of blood vessels. The thymus is abundantly supplied with blood. From the nearby thyroid, upper thoracic arteries and aorta, smaller and then numerous arterioles depart, feeding the gland.

Structure of the thymus

Arterioles are divided into:

  • lobular - supplying one of the lobes of the gland;
  • interlobular;
  • intralobular - located in the septal septa.

The peculiarity of the structure of the vessels that supply the thymus gland is a denser basal layer, which does not allow large protein formations - antigens - to penetrate the barrier. The arterioles inside the organ disintegrate into capillaries, which smoothly turn into venules - small vessels that carry venous blood out of the organ.

Innervation is carried out due to the sympathetic and parasympathetic systems, nerve trunks run along the blood vessels, forming plexuses surrounded by fibrous connective tissue.

Diseases of the thymus are rare, so many do not even know what functions it performs.

We'll tell you what diseases an ultrasound scan of the thymus gland can detect.

You can read about the reasons for the enlargement of the thymus gland in children. Should you worry?

Tissue structure

The darker layer inside each lobule is called the cortex and consists of an outer and internal zones formed by a dense cluster of cells - T-lymphocytes.

They are separated from the thymic capsule by epithelial reticulocytes, so tightly compressed that they completely isolate the cortex from the outside. These cells have processes with which they connect with underlying cells, forming peculiar cells. Lymphocytes are located in them, the number of which is huge.

Thymus tissue

The transition zone between the dark and light substance is called the cortico-medullary zone. This boundary is arbitrary and marks the transition of more differentiated thymocytes to the medulla.

The medulla is a light layer of the organ, consisting of epithelioreticulocytes and a small number of lymphocytes. Their origin is different - the main part is formed in the thymus itself, and a small amount is brought in by the blood flow from other lymphocytic organs. Reticulocytes of the medulla form circular clusters called Hassall's bodies.

In addition to the two main types of cells, the parenchyma of the thymus gland is rich in stellate cells that produce hormones, dendrites that select lymphocytes, and macrophages that protect the gland from foreign agents.

It is known that the thymus is most important for children, because it trains the immune system. undergoes some changes.

You can read more information about the thymus gland. Functions in adults and children.

Thymus: functions

There is still ongoing debate about which system of the body the thymus belongs to: endocrine, immune or hematopoietic (blood-forming).

In utero and in the first days after birth, the thymus gland is involved in the production of blood cells, but gradually this function loses its relevance and the immunological one comes to the fore.

It includes:

  • proliferation of lymphoid cells;
  • thymocyte differentiation;
  • selection of mature lymphocytes for suitability for use.

The cells entering the thymus from the bone marrow do not yet have specificity, and the task of the thymus gland is to “teach” thymocytes to recognize their own and foreign antigens. Differentiation occurs in the following directions: suppressive cells (suppressors), destroying cells (killers) and helping cells (helpers). Even mature thymocytes undergo careful selection. Those with poor discrimination of their own antigens are rejected. Such cells are destroyed without leaving the thymus into the bloodstream in order to prevent the development of autoimmune processes.

One more important function The thymus is the synthesis of hormones: thymulin, thymopoietin and thymosin. All of them are involved in the formation of immunity, and if their production is disrupted, the body’s defenses are significantly reduced, and autoimmune diseases, the risk of cancer pathologies increases significantly. Thymosin influences the formation of the musculoskeletal system by regulating mineral metabolism (calcium and phosphorus), thymulin is involved in endocrine processes.

Insufficient production of any thymus hormone causes immunodeficiency and contributes to severe infectious processes.

Thymus hormones influence puberty and indirectly on the level of androgens, estrogen and progesterone. The thymus is also involved in carbohydrate metabolism, it produces a substance whose action resembles insulin, thereby lowering blood sugar levels.

The thymus gland is an important organ, the importance of which is sometimes underestimated. When it changes immune status, frequent colds, activation opportunistic flora It is recommended to conduct a full examination, taking into account not only cellular immunity, but also the functions of the thymus.

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5. Thymus diseases

Microscopic structure of the thymus gland

The stroma of the thymus is of epithelial origin, originating from the epithelium of the anterior part of the primary intestine. Two cords originate from the third branchial arch and grow into the anterior mediastinum. Sometimes the thymic stroma is also formed by additional cords from the fourth pair of gill arches. Lymphocytes originate from blood stem cells that migrate to the thymus from the liver in the early stages of fetal development. Initially, proliferation of various blood cells occurs in the thymus tissue, but soon its function is reduced to the formation of T-lymphocytes. The thymus gland has a lobular structure; the tissue of the lobules is divided into the cortex and medulla. The cortex is located on the periphery of the lobule and appears dark in a histological microslide. The cortex contains arterioles and blood capillaries that have a blood-thymus barrier that prevents the introduction of antigens from the blood.

The cortex contains cells:

  • epithelial origin:
    • supporting cells: form the “framework” of the tissue, form the blood-thymus barrier;
    • stellate cells: secrete soluble thymic hormones - thymopoietin, thymosin and others, regulating the processes of growth, maturation and differentiation of T cells and the functional activity of mature cells of the immune system.
    • “nanny” cells: have invaginations in which lymphocytes develop;
  • hematopoietic cells:
    • lymphoid series: maturing T-lymphocytes;
    • macrophage series: typical macrophages, dendritic and interdigitating cells.

Directly under the capsule, dividing T-lymphoblasts predominate in the cellular composition. Deeper are the maturing T-lymphocytes, which gradually migrate to the medulla. The ripening process takes approximately 20 days. During their maturation, genes are rearranged and a gene encoding TCR is formed.

Next, they undergo positive selection: in interaction with epithelial cells, “functionally suitable” lymphocytes are selected, the TCR and its coreceptors of which are able to interact with HLA; During development, the lymphocyte differentiates into a helper or killer, i.e. either CD4 or CD8 remains on its surface. Next, in contact with stromal epithelial cells, cells capable of functional interaction are selected: CD8+ lymphocytes capable of receiving HLA I, and CD4+ lymphocytes capable of receiving HLA II.

The next stage - negative selection of lymphocytes - occurs at the border with the medulla. Dendritic and interdigitating cells - cells of monocyte origin - select lymphocytes capable of interacting with antigens of their own body and trigger their apoptosis.

The medulla mainly contains maturing T-lymphocytes. From here they migrate into the bloodstream of venules with high endothelium and disperse throughout the body. The presence of mature recirculating T-lymphocytes is also assumed here.

The cellular composition of the medulla is represented by supporting epithelial cells, stellate cells, and macrophages. There are also efferent lymphatic vessels and Hassall's corpuscles.

Blood supply and innervation of the thymus. The rr extend to the thymus from the internal mammary artery, aortic arch and brachiocephalic trunk. thymici. In the interlobular septa, they are divided into smaller branches, which penetrate into the lobules, where they branch to capillaries. The veins of the thymus drain into the brachiocephalic veins, as well as into the internal mammary veins.

Lymphatic capillaries of the thymus, which are more numerous in the cortex, form networks in the parenchyma of the organ, from which lymphatic vessels are formed that flow into the anterior mediastinal and tracheobronchial lymph nodes.

The thymic nerves are branches of the right and left vagus nerves, and also originate from the cervicothoracic (stellate) and superior thoracic ganglia of the sympathetic trunk.

2.3. Histology of the thymus

Externally, the thymus gland is covered with a connective tissue capsule. Partitions extend from it into the organ, dividing the gland into lobules. Each lobule contains a cortex and a medulla. The organ is based on epithelial tissue consisting of process cells - epithelioreticulocytes. All epithelioreticulocytes are characterized by the presence of desmosomes, tonofilaments and keratin proteins, products of the major histocompatibility complex on their membranes.

Epithelioreticulocytes, depending on their location, differ in shape and size, tinctorial features, hyaloplasm density, content of organelles and inclusions. Secretory cells of the cortex and medulla, non-secretory (or supporting) cells and cells of epithelial layered bodies - Hassall's bodies (Gassal's bodies) are described.

Secretory cells produce regulating hormone-like factors: thymosin, thymulin, thymopoietins. These cells contain vacuoles or secretory inclusions.

Epithelial cells in the subcapsular zone and outer cortex have deep invaginations in which lymphocytes are located, as in a cradle. The layers of cytoplasm of these epithelial cells - “feeders” or “nannies” between lymphocytes can be very thin and extended. Typically, such cells contain 10-20 lymphocytes or more.

Lymphocytes can move in and out of intussusceptions and form tight junctions with these cells. Nurse cells are capable of producing α-thymosin.

In addition to epithelial cells, auxiliary cells are distinguished. These include macrophages and dendritic cells. They contain products of the major histocompatibility complex and secrete growth factors (dendritic cells) that influence the differentiation of T lymphocytes.

Cortex - the peripheral part of the thymus lobules contains T-lymphocytes, which densely fill the lumens of the reticular epithelial framework. In the subcapsular zone of the cortex there are large lymphoid cells - T-lymphoblasts, which migrated here from the red bone marrow. They proliferate under the influence of thymosin secreted by epithelioreticulocytes. New generations of lymphocytes appear in the thymus every 6-9 hours. It is believed that T-lymphocytes of the cortex migrate into the bloodstream without entering the medulla. These lymphocytes differ in the composition of their receptors from the T-lymphocytes of the medulla. With the bloodstream, they enter the peripheral organs of lymphocytopoiesis - lymph nodes and spleen, where they mature into subclasses: antigen-reactive killers, helpers, suppressors. However, not all lymphocytes formed in the thymus enter the circulation, but only those that have undergone “training” and acquired specific cytoreceptors for foreign antigens. Lymphocytes that have cytoreceptors for their own antigens, as a rule, die in the thymus, which serves as a manifestation of the selection of immunocompetent cells. When such T-lymphocytes enter the bloodstream, an autoimmune reaction develops.

The cells of the cortex are in a certain way delimited from the blood by the blood-thymus barrier, which protects the differentiating lymphocytes of the cortex from excess antigens. It consists of endothelial cells of hemocapillaries with a basement membrane, a pericapillary space with single lymphocytes, macrophages and intercellular substance, as well as epithelioreticulocytes with their basement membrane. The barrier is selectively permeable to antigen. When the barrier is disrupted, single plasma cells, granular leukocytes and mast cells are also found among the cellular elements of the cortex. Sometimes foci of extramedullary myelopoiesis appear in the cortex.

The medulla of the thymus lobule on histological preparations has a lighter color, since it contains a smaller number of lymphocytes compared to the cortex. Lymphocytes in this zone represent a recirculating pool of T lymphocytes and can enter and exit the bloodstream through postcapillary venules.

The number of mitotically dividing cells in the medulla is approximately 15 times less than in the cortex. A feature of the ultramicroscopic structure of branched epithelioreticulocytes is the presence in the cytoplasm of grape-shaped vacuoles and intracellular tubules, the surface of which forms microprotrusions.

In the middle part of the medulla there are layered epithelial bodies (corpusculum thymicum) - Hassal's bodies. They are formed by concentrically layered epithelial oreticulocytes, the cytoplasm of which contains large vacuoles, keratin granules and bundles of fibrils. The number of these bodies in humans increases during puberty, then decreases. The function of the taurus has not been established.



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