Hexagonal Bipyramidal Mn3Ge5 Cluster and Its One-Dimensional Ferrimagnetic Sandwich Nanowire: Mn3Ge3 Rings as Structural Motifs.

Bipyramidal structures featuring planar rings serve as potential building blocks for one-dimensional (1D) nanostructures. Pure Ge atoms typically prefer to form three-dimensional rather than planar structures. Although a few-metal-doped bipyramids with pure Ge planar rings are predicted for constructing Ge-based 1D nanostructures, there is limited knowledge about those with both Ge and doped atoms on the same planar rings. Here, we report a hexagonal bipyramidal Mn3Ge5 cluster containing a Mn3Ge3 six-membered ring with the potential to construct a 1D germanium-based nanostructure. We investigated the structures and properties of Mn3Ge5-/0 using anion photoelectron spectroscopy and theoretical calculations. Mn3Ge5- has a C3v symmetric distorted hexagonal bipyramidal structure, while Mn3Ge5 has a C2v symmetric hexagonal bipyramidal structure. Chemical bonding analyses show that Mn3Ge5- could be considered as a [Mn3]V[Ge5]6- complex. First-principles calculations indicate that Mn3Ge5 may be used to construct a 1D ferrimagnetic [Mn3Ge5]∞ nanostructure.

Structures and Properties of Planar Ge3O3 Cluster and Its Buckled Honeycomb Two-Dimensional Nanostructure.

The discovery of graphene and its excellent properties inspired the search for more two-dimensional (2D) materials. Understanding the structures and properties of the smallest repeating units as well as crystal 2D materials is helpful for designing 2D materials. As germanium tends to form three-dimensional structures, the preparation of germanium-based 2D nanomaterials is still a challenge. Herein, we report a Ge3O3 cluster with the potential to construct a germanium oxide 2D nanostructure. We conduct a combined anion photoelectron spectroscopy and theoretical study on Ge3O3-/0. The structure of Ge3O3- is a Cs symmetric nonplanar six-membered ring, while that of Ge3O3 is a D3h symmetric planar six-membered ring. Chemical bonding analyses reveal that Ge3O3 exhibits π aromaticity. First-principle results suggest that a buckled honeycomb 2D nanostructure with a wide band gap of 3.14 eV may be produced based on Ge3O3, which is promising in optoelectronic applications especially in blue, violet, and ultraviolet regions.

Reduced Vrk2 expression is associated with higher risk of depression in humans and mediates depressive-like behaviors in mice.

BACKGROUND: Genome-wide association studies (GWAS) have reported single-nucleotide polymorphisms (SNPs) in the VRK serine/threonine kinase 2 gene (VRK2) showing genome-wide significant associations with major depression, but the regulation effect of the risk SNPs on VRK2 as well as their roles in the illness are yet to be elucidated. METHODS: Based on the summary statistics of major depression GWAS, we conducted population genetic analyses, epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to identify the functional SNPs regulating VRK2; we also carried out behavioral assessments, dendritic spine morphological analyses, and phosphorylated 4D-label-free quantitative proteomics analyses in mice with Vrk2 repression. RESULTS: We identified a SNP rs2678907 located in the 5' upstream of VRK2 gene exhibiting large spatial overlap with enhancer regulatory marks in human neural cells and brain tissues. Using luciferase reporter gene assays and eQTL analyses, the depression risk allele of rs2678907 decreased enhancer activities and predicted lower VRK2 mRNA expression, which is consistent with the observations of reduced VRK2 level in the patients with major depression compared with controls. Notably, Vrk2-/- mice exhibited depressive-like behaviors compared to Vrk2+/+ mice and specifically repressing Vrk2 in the ventral hippocampus using adeno-associated virus (AAV) lead to consistent and even stronger depressive-like behaviors in mice. Compared with Vrk2+/+ mice, the density of mushroom and thin spines in the ventral hippocampus was significantly altered in Vrk2-/- mice, which is in line with the phosphoproteomic analyses showing dysregulated synapse-associated proteins and pathways in Vrk2-/- mice. CONCLUSIONS: Vrk2 deficiency mice showed behavioral abnormalities that mimic human depressive phenotypes, which may serve as a useful murine model for studying the pathophysiology of depression.

LSD1: an emerging face in altering the tumor microenvironment and enhancing immune checkpoint therapy.

Dysregulation of various cells in the tumor microenvironment (TME) causes immunosuppressive functions and aggressive tumor growth. In combination with immune checkpoint blockade (ICB), epigenetic modification-targeted drugs are emerging as attractive cancer treatments. Lysine-specific demethylase 1 (LSD1) is a protein that modifies histone and non-histone proteins and is known to influence a wide variety of physiological processes. The dysfunction of LSD1 contributes to poor prognosis, poor patient survival, drug resistance, immunosuppression, etc., making it a potential epigenetic target for cancer therapy. This review examines how LSD1 modulates different cell behavior in TME and emphasizes the potential use of LSD1 inhibitors in combination with ICB therapy for future cancer research studies.

Lysine demethylase LSD1 delivered via small extracellular vesicles promotes gastric cancer cell stemness.

Several studies have examined the functions of nucleic acids in small extracellular vesicles (sEVs). However, much less is known about the protein cargos of sEVs and their functions in recipient cells. This study demonstrates the presence of lysine-specific demethylase 1 (LSD1), which is the first identified histone demethylase, in the culture medium of gastric cancer cells. We show that sEVs derived from gastric cancer cells and the plasma of patients with gastric cancer harbor LSD1. The shuttling of LSD1-containing sEVs from donor cells to recipient gastric cancer cells promotes cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2, and CD44. Additionally, sEV-delivered LSD1 suppresses oxaliplatin response of recipient cells in vitro and in vivo, whereas LSD1-depleted sEVs do not. Taken together, we demonstrate that LSD1-loaded sEVs can promote stemness and chemoresistance to oxaliplatin. These findings suggest that the LSD1 content of sEV could serve as a biomarker to predict oxaliplatin response in gastric cancer patients.

Anion Photoelectron Spectroscopy and Theoretical Studies of Ge3n+1O (n = 1-3) Clusters with the C3v Symmetric Ge3 Structural Unit.

We investigate Ge3n+1O-/0 (n = 1-3) clusters using anion photoelectron spectroscopy and theoretical calculations. The results show that the lowest energy structure of Ge4O- is a bent Cs symmetric trigonal bipyramidal structure, while Ge4O has a C3v symmetric trigonal bipyramidal structure. Ge7O- has two coexisting low-lying isomers, the first one can be viewed as a Ge2O unit interacting with a Ge5 trigonal bipyramid, the second one can be regarded as an O atom interacting with a Ge7 pentagonal bipyramid; whereas Ge7O has a C3v symmetric structure with a Ge atom and an O atom capping a Ge6 trigonal antiprism from the bottom and top, respectively. The structures of Ge10O- and Ge10O can be obtained by adding an O atom to different binding sites of a C3v symmetric Ge10. Chemical bonding analyses of Ge3n+1O (n = 1-3) reveal that the O atom interacts with its neighboring three Ge atoms forming one 4c-2e σ bond and two 4c-2e π bonds in the top Ge3O trigonal pyramid, while the terminal Ge atom forms one 4c-2e σ bond in the bottom Ge4 trigonal pyramid. The large HOMO-LUMO gaps of Ge3n+1O (n = 1-3) indicate that they have good stabilities. Ab initio molecular dynamics simulations suggest that both Ge7O and Ge10O are dynamically stable in general at 300 and 500 K. The current work suggests that the C3v symmetric Ge3 units and the insertion growth pattern may be viable for constructing 1D germanium oxide nanostructures with the chemical formula of Ge3n+1O.

Investigation of the Structures and Chemical Bonding of Mn2Ge6- and Mn2Ge7- Clusters via Anion Photoelectron Spectroscopy and Theoretical Calculations.

We present joint anion photoelectron spectroscopy and theoretical studies for Mn2Ge6- and Mn2Ge7-. Experimental results show that Mn2Ge6- and Mn2Ge7- have vertical electron detachment energies of 2.58 ± 0.08 and 2.88 ± 0.08 eV, respectively. Both Mn2Ge6- and Mn2Ge6 have Cs symmetric structures with a Mn atom attached to a pentagonal bipyramid MnGe6. Both Mn2Ge7- and Mn2Ge7 have C2v symmetric structures, which can be considered as two Mn2Ge4 tetragonal bipyramids sharing a MnGeMn face. According to chemical bonding analyses, Mn2Ge6 could be considered as a (MnII)(MnGe62-) complex. Theoretical calculations predict that the extension of Mn2Ge7 to Mn2nGe4n+3 may be able to produce a new type of Mn-doped germanium nanostructure.

Generation, secretion and degradation of cancer immunotherapy target PD-L1.

Cancer immunotherapy is a rapidly developing and effective method for the treatment of a variety of malignancies in recent years. As a significant immune checkpoint, programmed cell death 1 ligand 1 (PD-L1) and its receptor programmed cell death protein 1 (PD-1) play the most significant role in cancer immune escape and cancer immunotherapy. Though PD-L1 have become an important target for drug development and there have been various approved drugs and clinic trials targeting it, and various clinical response rate and adverse reactions prevent many patients from benefiting from it. In recent years, combination trials have become the main direction of PD-1/PD-L1 antibodies development. Here, we summarized PD-L1 biofunctions and key roles in various cancers along with the development of PD-L1 inhibitors. The regulators that are involved in controlling PD-L1 expression including post-translational modification, mRNA level regulation as well as degradation and exosome secretory pathway of PD-L1 were focused. This systematic summary may provide comprehensive understanding of different regulations on PD-L1 as well as a broad prospect for the search of the important regulator of PD-L1. The regulatory factors of PD-L1 can be potential targets for immunotherapy and increase strategies of immunotherapy in combination.

LSD1 deletion decreases exosomal PD-L1 and restores T-cell response in gastric cancer.

BACKGROUND: Histone lysine-specific demethylase 1 (LSD1) expression has been shown to be significantly elevated in gastric cancer (GC) and may be associated with the proliferation and metastasis of GC. It has been reported that LSD1 repressed tumor immunity through programmed cell death 1 ligand 1 (PD-L1) in melanoma and breast cancer. The role of LSD1 in the immune microenvironment of GC is unknown. METHODS: Expression LSD1 and PD-L1 in GC patients was analyzed by immunohistochemical (IHC) and Western blotting. Exosomes were isolated from the culture medium of GC cells using an ultracentrifugation method and characterized by transmission electronic microscopy (TEM), nanoparticle tracking analysis (NTA), sucrose gradient centrifugation, and Western blotting. The role of exosomal PD-L1 in T-cell dysfunction was assessed by flow cytometry, T-cell killing and enzyme-linked immunosorbent assay (ELISA). RESULTS: Through in vivo exploration, mouse forestomach carcinoma (MFC) cells with LSD1 knockout (KO) showed significantly slow growth in 615 mice than T-cell-deficient BALB/c nude mice. Meanwhile, in GC specimens, expression of LSD1 was negatively correlated with that of CD8 and positively correlated with that of PD-L1. Further study showed that LSD1 inhibited the response of T cells in the microenvironment of GC by inducing the accumulation of PD-L1 in exosomes, while the membrane PD-L1 stayed constant in GC cells. Using exosomes as vehicles, LSD1 also obstructed T-cell response of other cancer cells while LSD1 deletion rescued T-cell function. It was found that while relying on the existence of LSD1 in donor cells, exosomes can regulate MFC cells proliferation with distinct roles depending on exosomal PD-L1-mediated T-cell immunity in vivo. CONCLUSION: LSD1 deletion decreases exosomal PD-L1 and restores T-cell response in GC; this finding indicates a new mechanism with which LSD1 may regulate cancer immunity in GC and provides a new target for immunotherapy against GC.

Linolenic Acid-Metronidazole: a Compound Relieving Drug Resistance and Inhibiting Helicobacter pylori.

Metronidazole (Met) is the first choice for treating Helicobacter pylori (Hp). However, Hp is easy to resistant, making Met unable to be widely used. How to overcome Hp's Met resistance is still an issue. In this study, Met was used as the primary raw material with linolenic acid to prepare a novel compound-linolenic acid-metronidazole (Lla-Met). The MIC, minimum bactericidal concentration (MBC), colonization amount of Hp in gastric mucosa, etc., were evaluated, respectively. Lla-Met was successfully prepared by the detection of nuclear magnetic resonance, etc., and its MIC and MBC to Hp were 2~4 µg/mL, 8~16 µg/mL. Moreover, in vivo experiments, Lla-Met significantly reduced the colonization of drug-resistant Hp in gastric mucosa. In the toxicity test, Lla-Met inhibited rate to GES-1 and BGC823 cells were 15% at 128 µg/mL; the mice were administered 10 times treatment Lla-Met treatment (240 mg/kg), have no difference significant injuries were found in their stomach, liver, spleen, kidney, and weight. In addition, Hp G27 continued for 18 days in vitro with sub-Lla-Met concentration, G27 did not show drug resistance to Lla-Met; Lla-Met did not exert an effect on non-Hp species with 128 µg/mL; Compared with a neutral environment, when the acid concentration is 3.0, Lla-Met is not decomposed and has better stability. Conclusion: Lla-Met, a newly prepared compound, has relatively well antibacterial of Met-resistant and sensitive Hp, with a capability of overcoming the metronidazole resistance of Hp.

Photoelectron Spectroscopy and Theoretical Studies of Ge6MnO- Cluster with a MnV≡O Unit Interacting with a Double Aromatic Ge64- Ligand.

The structures and chemical bonding of Ge6MnO- are investigated using anion photoelectron spectroscopy and theoretical calculations. The lowest energy structure of Ge6MnO- is found to have a C5v symmetric structure with an O atom attached to a pentagonal bipyramidal MnGe6. Chemical bonding analyses reveal that Ge6MnO- can be considered as a [MnV≡O]3+[Ge64-] complex with two unpaired 3d electrons on Mn. The Ge64- ligand is highly stable in Ge6MnO- and exhibits double aromaticity with 10 delocalized σ electrons and 6 delocalized π electrons. Our calculations show that the Ge64- ligand could also form [CrIV≡O]2+[Ge64-] in Na2Ge6CrO and [FeIV≡O]2+[Ge64-] in Na2Ge6FeO. The results suggest the possibility of designing and synthesizing a series of stable high-valent metal oxide anionic species with the composition [M≡O]n+[Ge64-] in the gas phase or in the salt-stabilized bulk solid materials.

Identification of Ge═O Double Bonds in Planar MnGe3O and MnGe4O Clusters: Anion Photoelectron Spectroscopy and Ab Initio Calculations.

The structures, chemical bonding, and magnetic properties of MnGe3O-/0 and MnGe4O-/0 are investigated by photoelectron spectroscopy and ab initio calculations. The experimental vertical electron detachment energies of MnGe3O- and MnGe4O- are measured to be 2.06 ± 0.04 and 2.64 ± 0.04 eV, respectively. The structures of MnGe3O-/0 and MnGe4O-/0 can be viewed as evolved from quadrilateral MnGe3 or tetrahedral MnGe3. It is found that both MnGe3O- and MnGe3O have Cs symmetric planar structures with an O atom attached to quadrilateral MnGe3. The structure of MnGe4O- is nonplanar with an O atom and an additional Ge atom attached to tetrahedral MnGe3, while that of MnGe4O is planar with an O atom and an additional Ge atom attached to quadrilateral MnGe3. Chemical bonding analyses reveal the existence of Ge═O double bonds in MnGe3O and MnGe4O. Magnetic property analyses suggest that MnGe3O and MnGe4O are ferromagnetic with total spin magnetic moments of 5 µB.

Investigation of highly ferromagnetic Mn2Ge4 and Mn2Ge5 clusters via photoelectron spectroscopy and theoretical calculations.

We investigate the structures and properties of Mn2Ge4-/0 and Mn2Ge5-/0 by anion photoelectron spectroscopy and theoretical calculations. The vertical detachment energies (VDEs) of Mn2Ge4- and Mn2Ge5- are measured to be 2.69 eV and 2.49 eV, respectively. It is found that neutral Mn2Ge4 has an approximate quadrilateral bipyramidal structure with C2v symmetry and 11B2 electronic state. Neutral Mn2Ge5 has a pentagonal bipyramidal structure with C2v symmetry and 11B2 electronic state. The 4s-based molecular orbitals of the Mn atoms participate in the chemical bonding with the Ge4 and Ge5 fragments in Mn2Ge4 and Mn2Ge5. In Mn2Ge4, the two Mn atoms interact with the Ge4 moiety via four GeGeMn 3c-2e σ bonds. In Mn2Ge5, the two Mn atoms interact with the Ge5 moiety via one MnGeMn 3c-2e σ bond and four GeMnGe 3c-2e σ bonds. The analysis of magnetic properties reveals that both Mn2Ge4 and Mn2Ge5 exhibit highly ferromagnetic characteristics with a magnetic moment of 10 µB which mainly originated from the Mn atoms. These double Mn atom doped germanium clusters may provide new opportunities to design novel spintronic devices featuring high magnetic moments.

Observation of Aromatic Three-Membered Rings in Ge3C and Ge3O via Photoelectron Spectroscopy and Theoretical Calculations.

The structures and chemical bonding of Ge3C- and Ge3O- as well as their neutrals are explored with anion photoelectron spectroscopy and theoretical calculations. The vertical detachment energies of Ge3C- and Ge3O- are measured to be 1.51 ± 0.04 and 2.00 ± 0.04 eV, respectively. It is found that Ge3C-/0 have a C2v symmetric planar structure with the C atom interacting with three Ge atoms. Ge3O-/0 have the O atom interacting with two Ge atoms of the triangular Ge3 unit. Ge3O- has a Cs symmetric nonplanar structure, while Ge3O has a C2v symmetric planar structure. Theoretical results show that the multiconfigurational effects in Ge3C-/0 and Ge3O-/0 are insignificant. Chemical bonding analyses reveal that there exist the C-Ge3 π⊥ orbital interaction and two π aromatic Ge2C units in Ge3C. There are O-Ge3 π⊥ orbital interaction and one doubly aromatic Ge3 unit in Ge3O, but the π⊥ orbital interaction is relatively weak.

A joint experimental and theoretical study on structural, electronic, and magnetic properties of MnGen - (n = 3-14) clusters.

A systematic structure and property investigation of MnGen - (n = 3-14) was conducted by means of density functional theory coupled with mass-selected anion photoelectron spectroscopy. This combined theoretical and experimental study allows global minimum and coexistence structures to be identified. It is found that the pentagonal bipyramid shape is the basic framework for the nascent growth process of MnGen - (n = 3-10), and from n = 10, the endohedral structures can be found. For n = 12, the anion MnGe12 - cluster probably includes two isomers: a major isomer with a puckered hexagonal prism geometry and a minor isomer with a distorted icosahedron geometry. Specifically, the puckered hexagonal prism isomer follows the Wade-Mingos rules and can be suggested as a new kind of superatom with the magnetic property. Furthermore, the results of adaptive natural density partitioning and deformation density analyses suggest a polar covalent interaction between Ge and Mn for endohedral clusters of MnGe12 -. The spin density and natural population analysis indicate that MnGen - clusters have high magnetic moments localized on Mn. The density of states diagram visually shows the significant spin polarization for endohedral structures and reveals the weak interaction between the Ge 4p orbital and the 4s, 3d orbitals of Mn.

[Simultaneous determination of 13 hormones in Testis et Penis Cervi using QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry].

A reliable QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) analysis method was developed for the simultaneous determination of 13 steroid hormones(nrolone, androstenedione, methyltestosterone, testosterone, norethindrone, medroxyprogesterone, progesterone, diethylstilbestrol, hexan-stilbestrol, estradiol, estrotriol, cortisone, hydrocortisone) in Testis et Penis Cervi. The samples were extracted with methanol and purified by QuEChERS. Subsequently, the samples were separated by ACQUITY BEH C_(18) column and detected in the multiple reaction monitoring(MRM) mode under electrospray ionization in the positive and negative ion modes, respectively. Significant differences in the content of thirteen steroid hormones in Testis et Penis Cervi between the sika deer at different periods and the red deer were observed. The content of testosterone(10.88 µg·kg~(-1)) and hydrocortisone(12.82 µg·kg~(-1)) in Testis et Penis Cervi derived from rutting sika deer was significantly higher than the content of testosterone(1.05 µg·kg~(-1)) and hydrocortisone(0.73 µg·kg~(-1)) from antler growth stage. The content of progesterone in Testis et Penis Cervi derived from red deer was 6.07 µg·kg~(-1), significantly higher than that from sika deer. The content of progesterone in the testicle of red deer reached 27.46 µg·kg~(-1), 4.5 times greater than that in the penis of red deer. The sensitivity, accuracy, and precision of the method can meet the detection requirements, and the developed method is suitable for the measurement of hormones in animal-derived food.

LSD1 deletion represses gastric cancer migration by upregulating a novel miR-142-5p target protein CD9.

LSD1 (histone lysine specific demethylase 1) takes part in the physiological process of cell differentiation, EMT (epithelial-mesenchymal transition) and immune response. In this study, we found LSD1 expression in metastatic gastric cancer tissues was significantly higher than that in normal tissues. Furthermore, LSD1 deletion was found to suppress gastric cancer migration by decreasing intracellular miR-142-5p, which further led to the upregulation of migration suppressor CD9, a newly identified target of miR-142-5p. While LSD1 was reported as a demethylase of H3K4me1/2, H3K9me1/2 and several non-histone proteins, this is a new evidence for LSD1 as a functional regulator of miRNA. On the other hand, our data suggested that promoting the secretion of miR-142-5p using small extracellular vesicles as vehicles is a new mechanism for LSD1 abrogation to down-regulate intracellular miR-142-5p. Taken together, this study uncovered a new mechanism for LSD1 that can contribute to gastric cancer migration by facilitating miR-142-5p to target CD9.

A rapid and convenient derivatization method for quantitation of short-chain fatty acids in human feces by ultra-performance liquid chromatography/tandem mass spectrometry.

RATIONALE: Short-chain fatty acids (SCFAs) are associated with intestinal microbiota and diseases in humans. SCFAs have a low response in mass spectrometry, and in order to increase sensitivity, reduce sample consumption, shorten analysis time, and simplify sample preparation steps, a derivatization method was developed. METHODS: We converted seven SCFAs into amide derivatives with 4-aminomethylquinoline. The reaction occurred for 20 min at room temperature. The analytes were separated on a reversed-phase C18 column and quantitated in the positive ion electrospray ionization mode using multiple reaction monitoring. Acetic acid-d4 was used as the stable-isotope-labeled surrogate analyte for acetic acid in the working solutions, while the other stable-isotope-labeled standards were used as internal standards (ISs). RESULTS: Method validation showed that the intra-day and inter-day precision of quantitation for the seven SCFAs over the whole concentration range was ≤3.8% (n = 6). The quantitation accuracy ranged from 85.5% to 104.3% (n = 6). Most important, the collected feces were vortexed immediately with ethanol. CONCLUSIONS: This study provides a new derivatization method for a precise, accurate, and rapid quantitation of SCFAs in human feces using ultra-performance liquid chromatography/tandem mass spectrometry. This method successfully determined the concentration of SCFAs in human feces and could assist in the exploration of intestinal microbiota and diseases.

Natural protoberberine alkaloids, identified as potent selective LSD1 inhibitors, induce AML cell differentiation.

Natural protoberberine alkaloids were first identified and characterized as potent, selective and cellular active lysine specific demethylase 1 (LSD1) inhibitors. Due to our study, isoquinoline-based tetracyclic scaffold was identified as the key structural element for their anti-LSD1 activity, subtle changes of substituents attached to the core structure led to dramatic changes of the activity. Among these protoberberine alkaloids, epiberberine potently inhibited LSD1 (IC50 = 0.14 ± 0.01 µM) and was highly selective to LSD1 over MAO-A/B. Furthermore, epiberberine could induce the expression of CD86, CD11b and CD14 in THP-1 and HL-60 cells, confirming its cellular activity of inducing acute myeloid leukemia (AML) cells differentiation. Moreover, epiberberine prolonged the survival of THP-1 cells bearing mice and inhibited the growth of AML cells in vivo without obvious global toxicity. These findings give the potential application of epiberberine in AML treatment, and the isoquinoline-based tetracyclic scaffold could be used for further development of LSD1 inhibitors.

[48,XXYY syndrome: A report of four cases].

OBJECTIVE: To explore the clinical characteristics and prognosis of the 48,XXYY syndrome and gain a deeper insight into this condition. METHODS: This retrospective study included 4 cases of 48,XXYY syndrome confirmed between 2011 and 2018. We analyzed the general information, clinical manifestations, laboratory results, imaging features and outcomes of assisted reproductive technology (ART) of the patients and reviewed the relevant literature. RESULTS: The 4 patients with 48,XXYY syndrome were characterized by low literacy, soft texture and small volume of the testis, high levels of FSH and LH, and low level of serum T. Two of them were diagnosed with ejaculatory dysfunction and aspermia, and the other 2 with normal ejaculatory function but azoospermia. Biochemical analysis of seminal plasma indicated normal quantifications of both fructose and neutral α glucosidase. ART with donor sperm was performed for all the 4 cases and 3 of them got full-term babies. CONCLUSIONS: The 48,XXYY syndrome is often complicated by hypergonadotropic hypogonadism, with the clinical manifestations of aspermia or non-obstructive azoospermia. ART with donor sperm can be employed to help the patient with 48,XXYY syndrome get their non-biological offspring.