Room-temperature magnetoresistance in an all-antiferromagnetic tunnel junction.

Antiferromagnetic spintronics1-16 is a rapidly growing field in condensed-matter physics and information technology with potential applications for high-density and ultrafast information devices. However, the practical application of these devices has been largely limited by small electrical outputs at room temperature. Here we describe a room-temperature exchange-bias effect between a collinear antiferromagnet, MnPt, and a non-collinear antiferromagnet, Mn3Pt, which together are similar to a ferromagnet-antiferromagnet exchange-bias system. We use this exotic effect to build all-antiferromagnetic tunnel junctions with large nonvolatile room-temperature magnetoresistance values that reach a maximum of about 100%. Atomistic spin dynamics simulations reveal that uncompensated localized spins at the interface of MnPt produce the exchange bias. First-principles calculations indicate that the remarkable tunnelling magnetoresistance originates from the spin polarization of Mn3Pt in the momentum space. All-antiferromagnetic tunnel junction devices, with nearly vanishing stray fields and strongly enhanced spin dynamics up to the terahertz level, could be important for next-generation highly integrated and ultrafast memory devices7,9,16.

Identification of novel candidate pathogenic genes in pituitary stalk interruption syndrome by whole-exome sequencing.

Pituitary stalk interruption syndrome (PSIS) is a type of congenital malformation of the anterior pituitary, which leads to isolated growth hormone deficiency or multiple hypothalamic-pituitary deficiencies. Many genetic factors have been explored, but they only account for a minority of the genetic aetiology. To identify novel PSIS pathogenic genes, we conducted whole-exome sequencing with 59 sporadic PSIS patients, followed by filtering gene panels involved in pituitary development, holoprosencephaly and midline abnormality. A total of 81 heterozygous variants, distributed among 59 genes, were identified in 50 patients, with 31 patients carrying polygenic variants. Fourteen of the 59 pathogenic genes clustered to the Hedgehog pathway. Of them, PTCH1 and PTCH2, inhibitors of Hedgehog signalling, showed the most frequent heterozygous mutations (22%, seven missense and one frameshift mutations were identified in 13 patients). Moreover, five novel heterozygous null variants in genes including PTCH2 (p.S391fs, combined with p.L104P), Hedgehog acyltransferase (p.R280X, de novo), MAPK3 (p.H50fs), EGR4 (p.G22fs, combined with LHX4 p.S263N) and SPG11 (p.Q1624X), which lead to truncated proteins, were identified. In conclusion, genetic mutations in the Hedgehog signalling pathway might underlie the complex polygenic background of PSIS, and the findings of our study could extend the understanding of PSIS pathogenic genes.

Magnetoresistance and Hall resistivity of semimetal WTe2 ultrathin flakes.

This article reports the characterization of WTe2 thin flake magnetoresistance and Hall resistivity. We found it does not exhibit magnetoresistance saturation when subject to high fields, in a manner similar to their bulk characteristics. The linearity of Hall resistivity in our devices confirms the compensation of electrons and holes. By relating experimental results to a classic two-band model, the lower magnetoresistance values in our samples is demonstrated to be caused by decreased carrier mobility. The dependence of mobility on temperature indicates the main role of optical phonon scattering at high temperatures. Our results provide more detailed information on carrier behavior and scattering mechanisms in WTe2 thin films.

Body mass index had different effects on premenopausal and postmenopausal breast cancer risks: a dose-response meta-analysis with 3,318,796 subjects from 31 cohort studies.

BACKGROUND: There is sufficient evidence supporting a relationship between increased body mass index (BMI) and an increased risk for breast cancer among postmenopausal women. However, most studies have found a decreased risk for premenopausal breast cancer. This study was conducted to find out the different effects of BMI on the risk of breast cancer among premenopausal and postmenopausal women, and explore the potential factors that influence the associations. METHODS: A dose-response meta-analysis with 3,318,796 participants from 31 articles was conducted. Cohort studies that included BMI and corresponding breast cancer risk were selected through various databases including PubMed, Medline, Web of Science, the China National Knowledge Infrastructure (CNKI) and Chinese Scientific Journals (VIP). Random effects models were used for analyzing the data. RESULTS: The summary relative risks (RRs) were 1.33 (95%CI: 1.20-1.48) and 0.94(95%CI: 0.80-1.11) among postmenopausal and premenopausal women, respectively. The dose-response meta-analysis indicated a positive non-linear association between BMI and breast cancer risk among postmenopausal women, and compared to the mean level of the normal BMI category (21.5 kg/m2) the RR in total postmenopausal women were1.03 (95% CI: 1.02-1.05) per 1 kg/m2 increment. However, no statistically significant association among total premenopausal women was detected. In subgroup analysis among European premenopausal women, the summary RR was 0.79(95%CI: 0.70-0.88). The non-linear relationship showed a negative non-linear association between BMI and breast cancer risk among European premenopausal women. When compared to the mean level of the normal BMI category, the RRs were 0.98 (95%CI: 0.96-1.00) per 1 kg/m2 increment, respectively. CONCLUSIONS: In line with previous studies BMI had different effects on pre-menopausal and postmenopausal breast cancer risk. However, contrary to previous studies, a high BMI was not associated with decreased risk in total pre-menopausal women. More research is needed to better understand these differences.

[Relationship between uncoupling protein 1 gene promoter methylation and obesity in adult].

OBJECTIVE: To observe the relationship between the methylation status in promoter region of uncoupling protein 1( UCP1) gene and obesity. METHODS: A casecontrol study based on the hospital consisted 116 people was carried out, according to the body mass index( BMI), the subjects were divided into two groups, the overweight and obesity group with 50 samples( BMI≥24. 0) and the normal weight group with 66 samples( 18. 5≤BMI < 24), DNA samples were extracted from white blood cell and treated by hydrogen sulfite. Then mass spectrometry method was used to quantificationally detect the methylation level UCP1 gene promoter. The difference between the two groups was compared and the relationships between CpG sites and BMI were explored. RESULTS: Statistical analysis showed that the methylation differences between normal weight and overweight or obese group were not statistically significant, however, the CpG site UCP1-2_ Cp G_ 10. 11. 12. 13 had statistical significance in correlation coefficients with BMI according to multiple linear regression method( regression coefficient was 15. 370, P <0. 05). CONCLUSION: The UCP1 gene promoter methylation may be a factor for adult obesity.

Subcutaneously transplanted xenogeneic protein recruits treg cells and M2 macrophages to induce browning of inguinal white adipose tissue.

OBJECTIVE: To study whether subcutaneously embedding xenogeneic protein threads or synthetic polymer absorbable threads can improve obesity phenotypes and metabolic conditions, and to further explore its underlying mechanism. METHODS: Thirty-six 8-week-old ob/ob mice were randomly allocated to three groups, respectively, receiving catgut embedding, PGA thread embedding or sham treatment bilaterally to the groin. Individual parameters including weight, food intake, and core temperature are recorded and metabolism assessment, energy expenditure analysis, and PET/CT scanning are also performed at fixed timepoints. After surgical incision, the inguinal white adipose tissue was histologically examined and its expression profile was tested and compared among groups 4 weeks and 12 weeks after operation. RESULTS: Catgut embedding reduced weight gain and improved metabolic status in ob/ob mice. Browning of bilateral inguinal WAT (white adipose tissue) was induced after catgut embedding, with massive infiltration of Treg cells and M2 macrophages in the tissue slices of fat pads. IL-10 and TGF-ß released by Treg cells targeted macrophages and the induced M2 macrophages increased the expression of thermogenic and anti-inflammatory genes in fat. The secretion of catecholamines by polarized M2 macrophages led to the activation of ß3-AR-related pathways in adipocytes and the browning of adipose tissue. CONCLUSIONS: Abdominal subcutaneous catgut embedding has the potential to combat obesity through the induction of WAT browning mediated by infiltrated Treg cells and macrophages.

Engineering carbon semi-tubes supported platinum catalyst for efficient oxygen reduction electrocatalysis.

Innovation of catalyst structure is extremely important to develop the high-performance electrocatalysts for oxygen-reduction reaction (ORR). Herein, nitrogen-doped carbon semi-tube (N-CST) is used as a functional support for stabilizing the microwave-reduced Pt nanoparticles with an average size of ∼2.8 nm to synthesize the semi-tubular Pt/N-CST catalyst. The contribution of interfacial Pt-N bond between N-CST support and Pt nanoparticles with electrons transfer from N-CST support to Pt nanoparticles is found by electron paramagnetic resonance (EPR) and X-ray absorption fine structure (XAFS) spectroscopy. This bridged Pt-N coordination can simultaneously help ORR electrocatalysis and promote electrochemical stability. As a result, the innovative Pt/N-CST catalyst exhibits excellent catalytic performance, realizing ORR activity and electrochemical stability superior to the commercial Pt/C catalyst. Furthermore, density functional theoretical (DFT) calculations suggest that the interfacial Pt-N-C site with unique affinity of O∗ + OH∗ can provide new active routes for the enhanced electrocatalytic ORR capacity.

Plasma 25(OH)D Level is Associated with the Nucleic Acid Negative Conversion Time of COVID-19 Patients: An Exploratory Study.

Purpose: Vitamin D, an essential nutrient and a pleiotropic steroid hormone, has been reported to be associated with the risk and severity in patients infected with Coronavirus Disease-2019 (COVID-19). The role of vitamin D in predicting clinical outcome for COVID-19 patients is unknown. Here, we aimed to determine the prognostic value of plasma 25(OH)D level in COVID-19 patients. Patients and Methods: A total of 158 patients infected with novel COVID-19 Omicron variants in Shanghai were recruited in this study and were categorized into three groups by the tertile levels of plasma 25(OH)D. Plasma 25(OH)D level was determined along with routine blood tests related to liver and renal functions in newly diagnosed COVID-19 patients at admission. The nucleic acid negative conversion time of throat swab samples was evaluated as the primary clinical outcome. The prognostic value of clinical characteristics and plasma 25(OH)D level was assessed using the Kaplan-Meier plot and Cox proportional hazards regression tests. Results: Higher level of plasma 25(OH)D level in COVID-19 patients was independently associated with shorter nucleic acid negative conversion time from COVID-19 infection (multivariate adjusted HR: 0.54, 95%CI: 0.35-0.82, P=0.004, tertile 2 vs 1; multivariate adjusted HR: 0.60, 95%CI: 0.39-0.90, P=0.014, tertile 3 vs 1). Conclusion: Plasma 25(OH)D level may serve as an independent prognostic factor in COVID-19 patient. Our findings indicate the protective roles of vitamin D supplementation in the regiment of patients with COVID-19.

Multi-sites synergistic modulation in oxygen reduction electrocatalysis.

Revealing the types of and interplays among multiple active-sites in iron-nitrogen-carbon (FeNC) materials is of great significance for developing high-performance, Fe-based non-precious metal catalysts for oxygen reduction reaction (ORR). In this paper, a single-atom FeNC catalyst is prepared through high-temperature pyrolyzing of melamine foam (MF), iron phthalocyanine (FePc), phthalocyanine (Pc), and zinc (Zn)-salts composite. The catalyst is found to contain a variety of active-sites, including carbon atom next to pyridinic-N (pyridinicNC), Fe-N4 and pore defect. It is shown that MF with high N-content is responsible for the formation of the main pyridinicNC sites and in the meantime acts as the self-sacrificed template for framework of the catalyst. The presence of Pc can facilitate the formation of the predominant Fe-N4 sites, since the interplay between Pc and FePc results in a confinement of Fe-N4. Zn-salts serve as the pore-forming additives to create sufficient pore defects which can also anchor pyridinicNC and Fe-N4 structures. The results of density functional theory (DFT) calculations suggest that the multiple active-sites function synergistically to enable high-efficiency ORR electrocatalysis. The optimal FeNC catalyst shows superior ORR activity with a half-wave potential of ∼0.88 V (vs. RHE), as well as high methanol tolerance and electrochemical stability compared to the commercial carbon-supported platinum (Pt/C) catalyst.

Nonlinear amplification of microwave signals in spin-torque oscillators.

Spintronics-based microwave devices, such as oscillators and detectors, have been the subject of intensive investigation in recent years owing to the potential reductions in size and power consumption. However, only a few concepts for spintronic amplifiers have been proposed, typically requiring complex device configurations or material stacks. Here, we demonstrate a spintronic amplifier based on two-terminal magnetic tunnel junctions (MTJs) produced with CMOS-compatible material stacks that have already been used for spin-transfer torque memories. We achieve a record gain (|S11 | > 2) for input power on the order of nW (<-40 dBm) at an appropriate choice of the bias field direction and amplitude. Based on micromagnetic simulations and experiments, we describe the fundamental aspects driving the amplification and show the key role of the co-existence in microwave emissions of a dynamic state of the MTJ excited by a dc current and the injection locking mode driven by the microwave input signal. Our work provides a way to develop a class of compact amplifiers that can impact the design of the next generation of spintronics-CMOS hybrid systems.

Facile Synthesis of Surfactant-Induced Platinum Nanospheres with a Porous Network Structure for Highly Effective Oxygen Reduction Catalysis.

Developing a facile and eco-friendly method for the large-scale synthesis of highly active and stable catalysts toward oxygen reduction reaction (ORR) is very important for the practical application of proton exchange membrane fuel cells (PEMFCs). In this paper, a mild aqueous-solution route has been successfully developed for the gram-scale synthesis of three-dimensional porous Pt nanospheres (Pt-NSs) that are composed of network-structured nanodendrites and/or oval multipods. In comparison with the commercial Pt/C catalyst, X-ray photoelectron spectroscopy (XPS) demonstrates the dominant metallic-state of Pt and electrochemical impedance spectroscopy (EIS) indicates the substantial improvement of conductivity for the Pt-NSs/C catalyst. The surfactant-induced porous network nanostructure improves both the catalytic ORR activity and durability. The optimal Pt-NSs/C catalyst exhibits a half-wave potential of 0.898 V (vs. RHE), leading to the mass activity of 0.18 A mgPt -1 and specific activity of 0.68 mA cm-2 which are respectively 1.9 and 5.7 times greater than those of Pt/C. Moreover, the highly-active Pt-NSs/C catalyst shows a superior stability with the tenable morphology and the retained 78% of initial mass activity rather than the severe Pt aggregation and the only 58% retention of the commercial Pt/C catalyst after 10000 cycles.

Trastuzumab aggravates radiation induced cardiotoxicity in mice.

Some breast cancer patients with overexpression of human epidermal growth factor receptor 2 need both chest radiotherapy and targeted therapy with trastuzumab (TRZ). The cardiotoxicity associated with combined treatment potentially restricts the clinical benefits of antitumor therapy. There is no consensus on whether and how chest radiotherapy can be given in concurrent with TRZ at present, considering the cardiotoxicity. This study intends to establish an in vitro and in vivo heart injury model by irradiation and TRZ, analyze whether there is a synergistic effect in heart, and to explore the molecular changes. First, an in vitro irradiation model of H9C2 cardiomyocytes was established. The effects of TRZ and radiation on cardiomyocyte injury were observed by cell flow cytometry, CCK-8 test, Western blot, γ-H2AX fluorescence focus formation and cell Reactive Oxygen Species (ROS) content test. Second, the mouse heart injury model was set up by X-ray cardiac irradiation combined with TRZ. Six months later, the cardiac function was analyzed by small animal ultrasound and 18FDG-micro PET/CT. The morphological changes of heart tissue were assessed by histological section. We found that concurrent TRZ aggravates the injury effect of irradiation on cardiomyocytes in vitro. The influence of TRZ might be consequence of inhibiting Akt phosphorylation, promoting the excessive accumulation of ROS in cells and promoting intracellular DNA damage. In animal experiments, the dysfunction of diastolic and myocardial ischemia of mouse heart was observed by echocardiography and 18FDG-micro PET/CT, respectively; myocardial fibrosis and cardiomyocyte apoptosis were also observed. Therefore, our in vitro and in vivo experiments have revealed that TRZ combined irradiation caused more cardiotoxicity than irradiation or TRZ alone. These results suggested that the concurrent management of TRZ and radiotherapy should be carefully made in clinical practice, and more attention is needed on cardiac safety.

Temperature Dependence of Spin-Orbit Torques in Nearly Compensated Tb21Co79 Films by a Topological Insulator Sb2Te3.

Topological insulators (TIs) with spin-momentum-locked metallic surface states can exert giant spin-orbit torques, offering great potential in energy-efficient magnetic memory devices. In this work, temperature (T)-dependent SOT efficiencies are investigated in Sb2Te3/Ta/TbCo heterostructures with perpendicular magnetic anisotropy. The spin Hall angle θSH is around 0.16 at room temperature (RT), which is much higher than that of the control sample without TI. Moreover, as T decreases from RT down to 10 K, θSH exhibits a conspicuous 5-fold enhancement. Detailed analysis indicates that the θSH enhancement at reduced temperatures mainly results from the improved spin-polarized surface states, as evidenced from the continuously increased ratio of surface-to-bulk conduction. The θSH difference between 20 and 10 nm Sb2Te3 gradually shrinks with the increase of T, which is due to the increase of bulk state contribution. Our findings provide a deep insight into the spin transport mechanisms and robust charge-spin conversion in TIs.

A 3 pJ/bit free space optical interlink platform for self-powered tetherless sensing and opto-spintronic RF-to-optical transduction.

Tetherless sensors have long been positioned to enable next generation applications in biomedical, environmental, and industrial sectors. The main challenge in enabling these advancements is the realization of a device that is compact, robust over time, and highly efficient. This paper presents a tetherless optical tag which utilizes optical energy harvesting to realize scalable self-powered devices. Unlike previous demonstrations of optically coupled sensor nodes, the device presented here amplifies signals and encodes data on the same optical beam that provides its power. This optical interrogation modality results in a highly efficient data link. These optical tags support data rates up to 10 Mb/s with an energy consumption of ~ 3 pJ/bit. As a proof-of-concept application, the optical tag is combined with a spintronic microwave detector based on a magnetic tunnel junction (MTJ). We used this hybrid opto-spintronic system to perform self-powered transduction of RF waves at 1 GHz to optical frequencies at ~ 200 THz, while carrying an audio signal across (see Supplementary Data for audio files).

Decoration of Ru/RuO2 hybrid nanoparticles on MoO2 plane as bifunctional electrocatalyst for overall water splitting.

Hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are the two branches of artificial overall water splitting (OWS), in which the reaction efficiency usually depends on different specific catalysts. Although effective bifunctional electrocatalyst for OWS (HER and OER) are highly desired, designing and constructing such suitable materials is full of challenges to overcome several difficulties, involving slow kinetics, differences in catalytic mechanisms, large overpotential values, and low round-trip efficiencies. In this work, we reported a new bifunctional electrocatalyst Ru/RuO2-MoO2 catalyst (RRMC) via a redox solid phase reaction (RSPR) strategy to achieve the high electrocatalytic activity of OWS. Briefly, due to the restricted transport behavior of atoms in solid state precursor, the designed redox reaction occurred between the adjacent part of RuO2 and MoS2, forming Ru/RuO2 hybrid NPs and MoO2 plane. Therefore, the newly formed Ru/RuO2 hybrid NPs and MoO2 plane were tightly combined and used as an electrocatalyst for OWS. Benefiting from the exposed active sites and optimized electronic structure, the RRMC sample annealed at 500 °C (RRMC-500) exhibited low overpotential for HER (18 mV) and for OER (260 mV) at 10 mA cm-2 under alkaline conditions. Especially, a low cell voltage of 1.54 V was required at 10 mA cm-2 under alkaline condition.

Proximity effect of a two-dimensional van der Waals magnet Fe3GeTe2 on nickel films.

Recent advances in two-dimensional van der Waals (2D vdW) magnets provide new platforms to study their magnetism in reduced dimensions. However, most of the studies performed to date have been limited to low temperatures. Here, we report the proximity effect of a 2D vdW magnet Fe3GeTe2 (FGT) on nickel (Ni) films at room temperature. Ferromagnetic resonance measurements show that FGT can increase the perpendicular magnetic anisotropy (PMA) and magnetic damping of the adjacent Ni film. Such an interfacial effect is observed at room temperature, and becomes more pronounced as the temperature decreases. A similar effect is also achieved in another 2D heterostructure of Cr2Ge2Te6/Ni, implying its universality in a variety of 2D magnetic materials. Our work provides a new approach for utilizing 2D magnets in spintronics at room temperature.

ITGBL1 promotes cell migration and invasion through stimulating the TGF-ß signalling pathway in hepatocellular carcinoma.

OBJECTIVES: Integrin beta-like 1 (ITGBL1) is involved in the migration and invasion of several cancers; however, its roles in the development and progression of hepatocellular carcinoma (HCC) remain largely unknown. MATERIALS AND METHODS: Immunohistochemistry staining was used to investigate the expression pattern of ITGBL1 and its prognostic values in HCC patients. The transwell, wound-healing assays, xenograft and orthotopic mouse models were employed to determine the effects of ITGBL1 on HCC cell migration and invasion in vitro and in vivo. The biological mechanisms involved in cell migration and invasion caused by ITGBL1 were determined with Western blotting and RT-PCR methods. RESULTS: ITGBL1 expression was significantly increased in HCC tissues compared to adjacent normal tissues. Patients with higher ITGBL1 expression were associated with more reduced overall survival. ITGBL1 overexpression promoted migration and invasion in SMMC-7721 and HepG2 cells in vitro and in vivo, whereas knockdown or knockout ITGBL1 in CSQT-2 cells significantly reduced cell migration and invasion abilities. In SMMC-7721 cells, ITGBL1 overexpression stimulated TGF-ß/Smads signalling pathway, along with the KRT17 and genes involved in the epithelial-mesenchymal transition (EMT). In contrast, ITGBL1 knockout inhibited the TGF-ß/Smads signalling pathway in CSQT-2 cells. CONCLUSIONS: These findings suggested that ITGBL1 promoted migration and invasion in HCC cells by stimulating the TGF-ß/Smads signalling pathway. ITGBL1 could be a promising prognostic biomarker, as well as a potential therapeutic target in HCC.

Giant Piezospintronic Effect in a Noncollinear Antiferromagnetic Metal.

One of the main bottleneck issues for room-temperature antiferromagnetic spintronic devices is the small signal read-out owing to the limited anisotropic magnetoresistance in antiferromagnets. However, this could be overcome by either utilizing the Berry-curvature-induced anomalous Hall resistance in noncollinear antiferromagnets or establishing tunnel-junction devices based on effective manipulation of antiferromagnetic spins. In this work, the giant piezoelectric strain modulation of the spin structure and the anomalous Hall resistance in a noncollinear antiferromagnetic metal-D019 hexagonal Mn3 Ga-is demonstrated. Furthermore, tunnel-junction devices are built with a diameter of 200 nm to amplify the maximum tunneling resistance ratio to more than 10% at room-temperature, which thus implies significant potential of noncollinear antiferromagnets for large signal-output and high-density antiferromagnetic spintronic device applications.

Electric Field-Tunable Giant Magnetoresistance (GMR) Sensor with Enhanced Linear Range.

The operation mechanism of giant magnetoresistance (GMR) sensors relies on the linear response of the magnetization direction to an external magnetic field. Since the magnetic anisotropy of ferromagnetic layers can be manipulated by a strain-mediated magnetoelectric coupling effect, we propose a tunable GMR magnetic field sensor design that allows for voltage tuning of the linear range and sensitivity. A spin valve structure Ru/CoFe/Cu/CoFe/IrMn/Ru is grown on a PMN-PT (011) substrate, and the magnetization directions of ferromagnetic layers can be controlled by an electric field. An adjustable linear magnetoresistance is therefore induced. Based on the magnetoelectric coupling effect and spin valve, we prepared tunable GMR magnetic field sensors with bridge structures. The linear sensing range of a DC magnetic field is enhanced 6 times by applying an electric field of 14 kV/cm. The electrically tunable GMR sensor fulfills the requirements to work at different magnetic field ranges in the same configuration, therefore exhibiting great potential for applications in the Internet of things.

Genome-wide methylation study of whole blood cells DNA in men with congenital hypopituitarism disease.

Congenital hypopituitarism (CH) is a relatively rare disease that is characterized by the deficiency of one or more hormones secreted by the pituitary gland, which leads to metabolic disorders, amenorrhea and infertility. However, the underlying molecular mechanisms of CH have not yet been fully elucidated. The present study evaluated the genome­wide methylation level of whole blood DNA in 12 patients with CH and 12 age­matched controls using Illumina Human Methylation 450 array, in order to determine the roles of epigenetic regulation in the pathogenesis of CH. The results demonstrated that the methylation levels of 51 CpG sites were significantly different between the patients with CH and the controls. Functional enrichment analysis identified that the aberrant methylated genes were enriched in gene sets associated with metabolic or cellular process, immune system process and reproduction. In addition, two CpG sites on genes LIM domain kinase 2 (LIMK2) and piwi­like RNA­mediated gene silencing 2 (PIWIL2), which are involved in spermatogenesis and/or testicular development, were identified to be hypermethylated in male patients with CH. The hypermethylation of these sites was further validated in another 40 patients with CH and 40 matched controls with a quantitative bisulfite pyrosequencing method, and the methylation levels of these two loci demonstrated promising diagnostic capacities for CH. The present results suggested that aberrant methylation of genes may be involved in the pathogenesis of CH, and hypermethylation of LIMK2 and PIWIL2 may contribute to the infertility of male patients with CH. Further studies are required to elucidate the underlying mechanisms of the epigenetic regulation of these genes.