Structures of the ADGRG2-Gs complex in apo and ligand-bound forms.

Adhesion G protein-coupled receptors are elusive in terms of their structural information and ligands. Here, we solved the cryogenic-electron microscopy (cryo-EM) structure of apo-ADGRG2, an essential membrane receptor for maintaining male fertility, in complex with a Gs trimer. Whereas the formations of two kinks were determinants of the active state, identification of a potential ligand-binding pocket in ADGRG2 facilitated the screening and identification of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate and deoxycorticosterone as potential ligands of ADGRG2. The cryo-EM structures of DHEA-ADGRG2-Gs provided interaction details for DHEA within the seven transmembrane domains of ADGRG2. Collectively, our data provide a structural basis for the activation and signaling of ADGRG2, as well as characterization of steroid hormones as ADGRG2 ligands, which might be used as useful tools for further functional studies of the orphan ADGRG2.

Activation of PTH1R alleviates epididymitis and orchitis through Gq and ß-arrestin-1 pathways.

Inflammation in the epididymis and testis contributes significantly to male infertility. Alternative therapeutic avenues treating epididymitis and orchitis are expected since current therapies using antibiotics have limitations associated to side effects and are commonly ineffective for inflammation due to nonbacterial causes. Here, we demonstrated that type 1 parathyroid hormone receptor (PTH1R) and its endogenous agonists, parathyroid hormone (PTH) and PTH-related protein (PTHrP), were mainly expressed in the Leydig cells of testis as well as epididymal epithelial cells. Screening the secretin family G protein-coupled receptor identified that PTH1R in the epididymis and testis was down-regulated in mumps virus (MuV)- or lipopolysaccharide (LPS)-induced inflammation. Remarkably, activation of PTH1R by abaloparatide (ABL), a Food and Drug Administration-approved treatment for postmenopausal osteoporosis, alleviated MuV- or LPS-induced inflammatory responses in both testis and epididymis and significantly improved sperm functions in both mouse model and human samples. The anti-inflammatory effects of ABL were shown to be regulated mainly through the Gq and ß-arrestin-1 pathway downstream of PTH1R as supported by the application of ABL in Gnaq± and Arrb1-/- mouse models. Taken together, our results identified an important immunoregulatory role for PTH1R signaling in the epididymis and testis. Targeting to PTH1R might have a therapeutic effect for the treatment of epididymitis and orchitis or other inflammatory disease in the male reproductive system.

Highly Luminescent Earth-Benign Organometallic Manganese Halide Crystals with Ultrahigh Thermal Stability of Emission from 4 to 623 K.

The phosphor-converted light-emitting diode (PC-LED) has become an indispensable solid-state lighting and display technologies in the modern society. Nevertheless, the use of scarce rare-earth elements and the thermal quenching (TQ) behavior are still two most crucial issues yet to be solved. Here, this work successfully demonstrates a highly efficient and thermally stable green emissive MnI2 (XanPO) crystals showing a notable photoluminescence quantum yield (PLQY) of 94% and a super TQ resistance from 4 to 623 K. This unprecedented superior thermal stability is attributed to the low electron-phonon coupling and the unique rigid crystal structure of MnI2 (XanPO) over the whole temperature range based on the temperature-dependent photoluminescence (PL) and single crystal X-ray diffraction (SCXRD) analyses. Considering these appealing properties, green PC-LEDs with a power efficacy of 102.5 lm W-1 , an external quantum efficiency (EQE) of 22.7% and a peak luminance up to 7750 000 cd m-2 are fabricated by integrating MnI2 (XanPO) with commercial blue LEDs. Moreover, the applicability of MnI2 (XanPO) in both micro-LEDs and organic light-emitting diodes (OLEDs) is also demonstrated. In a nutshell, this study uncovers a candidate of highly luminescent and TQ resistant manganese halide suitable for a variety of emission applications.

Highly Efficient MAPbI3 -Based Quantum Dots Exhibiting Unusual Nonblinking Single Photon Emission at Room Temperature.

Highly emissive semiconductor nanocrystals, or so-called quantum dots (QDs) possess a variety of applications from displays and biology labeling, to quantum communication and modern security. Though ensembles of QDs have already shown very high photoluminescent quantum yields (PLQYs) and have been widely utilized in current optoelectronic products, QDs that exhibit high absorption cross-section, high emission intensity, and, most important, nonblinking behavior at single-dot level have long been desired and not yet realized at room temperature. In this work, infrared-emissive MAPbI3 -based halide perovskite QDs is demonstrated. These QDs not only show a ≈100% PLQY at the ensemble level but also, surprisingly, at the single-dot level, display an extra-large absorption cross-section up to 1.80 × 10-12 cm2 and non-blinking single photon emission with a high single photon purity of 95.3%, a unique property that is extremely rare among all types of quantum emitters operated at room temperature. An in-depth analysis indicates that neither trion formation nor band-edge carrier trapping is observed in MAPbI3 QDs, resulting in the suppression of intensity blinking and lifetime blinking. Fluence-dependent transient absorption measurements reveal that the coexistence of non-blinking behavior and high single photon purity in these perovskite QDs results from a significant repulsive exciton-exciton interaction, which suppresses the formation of biexciton, and thus greatly reduces photocharging. The robustness of these QDs is confirmed by their excellent stability under continuous 1 h electron irradiation in high-resolution transmission electron microscope inspection. It is believed that these results mark an important milestone in realizing nonblinking single photon emission in semiconductor QDs.

The Immunoscore system predicts prognosis after liver metastasectomy in colorectal cancer liver metastases.

BACKGROUND: The Immunoscore was initially established to evaluate the prognosis of stage I/II/III colorectal cancer patients. However, the feasibility of the Immunoscore for the prognosis of colorectal cancer liver metastases (CRCLM) has not been reported. METHODS: Liver metastases in 249 CRCLM patients were retrospectively analyzed. The Immunoscore was assessed according to the counts and densities of CD3+ and CD8+ T cells in the central- and peritumoral areas by immunohistochemistry. The prognostic role of the Immunoscore for relapse-free survival (RFS) and overall survival (OS) was analyzed with Kaplan-Meier curves and Cox multivariate models, and confirmed via an internal validation. Receiver operating characteristic (ROC) curves were plotted to compare the prognostic values of the Immunoscore and the clinical risk score (CRS) system. RESULTS: CRCLM patients with high Immunoscores (> 2) had significantly longer RFS [median RFS (95% confidence interval; 95% CI) 21.4 (7.8-35.1) vs. 8.7 (6.8-10.5) months, P < 0.001] and OS [median OS (95% CI): not reached vs. 28.7 (23.2-34.2) months, P < 0.001] than those with low Immunoscores (≤ 2). After stratification by CRS, the Immunoscore retained a statistically significant prognostic value for OS. The areas under the ROC curves (AUROCs) of the Immunoscore and the CRS system for RFS were 0.711 [95% CI 0.642-0.781] and 0.675[95% CI 0.601-0.749] (P = 0.492), whereas the AUROC of the Immunoscore system for OS was larger than that of the CRS system [0.759 (95% CI 0.699-0.818) vs. 0.660 (95% CI 0.592-0.727); P = 0.029]. CONCLUSIONS: The Immunoscore of liver metastases can be applied to predict the prognosis of CRCLM patients following liver resection.

[Collagenase clostridium histolyticum for Peyronie's disease: A new minimally invasive and effective treatment].

The treatment of Peyronie's disease has been a challenge to urologists, as most of the current oral medications are considered hardly valid and the rest of the therapies require strict control of indications, some of which remain controversial, while the final surgical option may be associated with complications such as penile shortening or erectile dysfunction. Collagenase clostridium histolyticum has been proved to be effective in dissolving the penile cavernosal plaque and approved by the Food and Drug Administration of the USA as the first drug to be used for the treatment of Peyronie's disease. This article presents an introduction to the characteristics, safety, efficacy, and procedures of this new treatment, which may benefit urologists and the patients with Peyronie's disease.

[Microdissection testicular sperm extraction for patients with nonmosaic Klinefelter syndrome: A report of 143 cases].

OBJECTIVE: To investigate the clinical application and outcomes of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS). METHODS: A total of 143 nonmosaic KS patients underwent micro-TESE in the Center of Reproductive Medicine of Peking University Third Hospital between July 2012 and August 2016. We analyzed their clinical and follow-up data and evaluated the outcomes. RESULTS: Spermatozoa were successfully retrieved from the testicular tissue in 44.76% (64/143) of the patients, 84.4% (54/64) by unilateral and 15.6% (10/64) by bilateral micro-TESE. Seventy-five of the KS patients were followed up in the years of 2014 and 2015. Of the 34 patients with successful sperm retrieval, 73.52% (25/34) achieved clinical pregnancy and 8 boys and 8 girls were already born in 14 of the 25 cases. CONCLUSIONS: The micro-TESE is a useful method for sperm retrieval in nonmosaic KS patients, with high rates of sperm retrieval, clinical pregnancy, and birth of biological offspring.

Sperm retrieval outcomes of contralateral testis in men with nonobstructive azoospermia and unsuccessful unilateral microdissection testicular sperm extraction.

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Long-term tadalafil once daily in Chinese men with erectile dysfunction: a 2-year final analysis of a post-marketing, multicenter, randomized, open-label trial.

The long-term safety and effectiveness of once-daily tadalafil is crucial, but limited data are available in Chinese patients with erectile dysfunction (ED). In this post-marketing, multicenter, randomized, open-label trial with 2-year follow-up, 635 ED cases were randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months, of whom 580 continued once-daily tadalafil 5 mg for 21 months. Treatment-emergent adverse events in the 12-month and 24-month period were similar, with the most common being viral upper respiratory tract infection, upper respiratory tract infection, and headache. Significant improvement from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) score was detected at month 12 (least squares mean [LSM] change: 7.9, 95% confidence interval [CI]: 7.5-8.4, P < 0.001) and was maintained to month 24 (LSM change: 8.6, 95% CI: 8.1-9.0, P < 0.001). The proportions of patients regaining normal erectile function (IIEF-EF score ≥26) were 43.7% and 48.0% at months 12 and 24, respectively. Global Assessment Questionnaire results showed improved erection function in 97.5% of patients and improved ability to engage in sexual activity in 95.9% of patients at month 12; these values were 96.1% and 95.0% at month 24, respectively. The quality of sexual life score based on the Sexual Life Quality Questionnaire (SLQQ) was increased by 52.2% at month 12 and by 55.3% at month 24 (both P < 0.001). The treatment satisfaction score determined by SLQQ (mean ± standard deviation) was 62.4 ± 21.0 at month 12 versus 65.9 ± 20.2 at month 24. Two-year daily application of tadalafil 5 mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

Factors influencing the sperm retrieval rate of microdissection testicular sperm extraction in patients with nonmosaic Klinefelter syndrome.

To investigate the factors affecting the sperm retrieval rate of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS), 64 patients with nonmosaic KS who underwent micro-TESE in the Center for Reproductive Medicine of Peking University Third Hospital (Beijing, China) between January 2016 and December 2017 were included in the study. Data on medical history, physical examination and laboratory examination results, and micro-TESE outcomes were collected. Patients were divided into two groups according to micro-TESE outcomes. The following factors were compared between the two groups by the Mann‒Whitney U test or Student's t-test based on the distribution (nonnormal or normal) of the factors: age, testicular size, follicle-stimulating hormone level, luteinizing hormone level, testosterone level, and anti-Müllerian hormone level. The overall success rate of sperm retrieval was 50.0%. Correlation analysis showed that testicular volume was positively correlated with testosterone level. Using a logistic regression model, age and anti-Müllerian hormone levels were found to be better predictors for the sperm retrieval rate than the other parameters.

Epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation.

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.

Development of a predictive model for increasing sperm retrieval success by microdissection testicular sperm extraction in patients with nonobstructive azoospermia.

Microdissection testicular sperm extraction (micro-TESE) is widely used to treat nonobstructive azoospermia. However, a good prediction model is required to anticipate a successful sperm retrieval rate before performing micro-TESE. This retrospective study analyzed the clinical records of 200 nonobstructive azoospermia patients between January 2021 and December 2021. The backward method was used to perform binary logistic regression analysis and identify factors that predicted a successful micro-TESE sperm retrieval. The prediction model was constructed using acquired regression coefficients, and its predictive performance was assessed using the receiver operating characteristic curve. In all, 67 patients (sperm retrieval rate: 33.5%) underwent successful micro-TESE. Follicle-stimulating hormone, anti-Müllerian hormone, and inhibin B levels varied significantly between patients who underwent successful and unsuccessful micro-TESE. Binary logistic regression analysis yielded the following six predictors: anti-Müllerian hormone (odds ratio [OR] = 0.902, 95% confidence interval [CI]: 0.821-0.990), inhibin B (OR = 1.012, 95% CI: 1.001-1.024), Klinefelter's syndrome (OR = 0.022, 95% CI: 0.002-0.243), Y chromosome microdeletion (OR = 0.050, 95% CI: 0.005-0.504), cryptorchidism with orchiopexy (OR = 0.085, 95% CI: 0.008-0.929), and idiopathic nonobstructive azoospermia (OR = 0.031, 95% CI: 0.003-0.277). The prediction model had an area under the curve of 0.720 (95% CI: 0.645-0.794), sensitivity of 65.7%, specificity of 72.2%, Youden index of 0.379, and cut-off value of 0.305 overall, indicating good predictive value and accuracy. This model can assist clinicians and nonobstructive azoospermia patients in decision-making and avoiding negative micro-TESE results.

Psychological status of infertile men during the Coronavirus Disease 2019 Pandemic in China: a cross-sectional investigation.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has had a widespread and profound impact on people's mental health. The factors associated with mental symptoms among men diagnosed with infertility, a disease closely related to psychological conditions, remain unclear. The aim of this study is to investigate the risk factors associated with mental symptoms among infertile Chinese men during the pandemic. RESULTS: A total of 4,098 eligible participants were recruited in this cross-sectional, nationwide study, including 2,034 (49.6%) with primary infertility and 2,064 (50.4%) with secondary infertility. The prevalence of mental health conditions was 36.3%, 39.6%, and 6.7% for anxiety, depression, and post-pandemic stress, respectively. Sexual dysfunction is associated with a higher risk with adjusted odds ratios (ORs) of 1.40 for anxiety, 1.38 for depression, and 2.32 for stress. Men receiving infertility drug therapy displayed a higher risk for anxiety (adjusted OR, 1.31) and depression (adjusted OR, 1.28) symptoms, while those receiving intrauterine insemination had a lower risk of anxiety (adjusted OR, 0.56) and depression (adjusted OR, 0.55) symptoms. CONCLUSION: The COVID-19 pandemic has had a significant psychological impact on infertile men. Several psychologically vulnerable populations were identified, including individuals with sexual dysfunction, respondents receiving infertility drug therapy, and those experiencing control measures for COVID-19. The findings provide a comprehensive profile of the mental health status of infertile Chinese men during the COVID-19 outbreak and provide potential psychological intervention strategies.

RéSUMé: CONTEXTE: L'épidémie de maladie à coronavirus 2019 (COVID-19) a eu un impact étendu et profond sur la santé mentale des gens. Les facteurs associés aux symptômes mentaux chez les hommes diagnostiqués comme infertiles, une maladie étroitement liée aux conditions psychologiques, restent flous. L'objectif de cette étude est d'étudier les facteurs de risque associés aux symptômes mentaux chez les hommes chinois infertiles pendant la pandémie. RéSULTATS: Au total, 4 098 participants admissibles ont été recrutés dans cette étude transversale à l'échelle nationale, dont 2 034 (49,6%) présentaient une infertilité primaire et 2 064 (50,4%) une infertilité secondaire. La prévalence des problèmes de santé mentale était respectivement de 36,3 %, 39,6 % et 6,7 % pour l'anxiété, la dépression, et le stress postpandémique. La dysfonction sexuelle est associée à un risque plus élevé avec des odds ratios ajustés (OR) de 1,40 pour l'anxiété, 1,38 pour la dépression et 2,32 pour le stress. Les hommes recevant un traitement médicamenteux contre l'infertilité présentaient un risque plus élevé de symptômes d'anxiété (OR ajusté, 1,31) et de dépression (OR ajusté, 1,28), alors que ceux dont le traitement consistait à faire des inséminations intra-utérines présentaient un risque plus faible de symptômes d'anxiété (OR ajusté, 0,56) et de dépression (OR ajusté, 0,55). CONCLUSIONS: La pandémie de COVID-19 a eu un impact psychologique important sur les hommes infertiles. Plusieurs populations psychologiquement vulnérables ont été identifiées, notamment les personnes souffrant de dysfonction sexuelle, les hommes recevant un traitement médicamenteux contre l'infertilité, et ceux subissant des mesures de contrôle de la COVID-19. Les résultats fournissent un profil complet de l'état de santé mentale des hommes Chinois infertiles pendant l'épidémie de COVID-19 et fournissent des stratégies potentielles d'intervention psychologique.

A retrospective cohort study of geographic differences in the semen of 1,012 sperm donors in China.

Background: Male reproductive health has become a serious public health concern, and semen quality is essential to male reproduction. We aimed to investigate geographical differences in the semen quality of sperm donors from northern and southern China by enrolling donors across the country. Methods: A total of 1,012 sperm donors were enrolled in this study between 2015 and 2019. Donors were first divided into two parts based on their birthplace according to the "Qinling-Huaihe" line, and secondly, by their residential latitude. Finally, donors were re-classified into two groups (typically north and south) which contained 667 samples. Results: Statistically significant differences in sperm concentration were observed among men from different latitudes in China (P=0.04). The sperm concentrations of males from 18° to 27° north latitude were significantly lower than those from 36° to 45° and 45° to 54° [median 131, 134, and 146, respectively, P=0.021 (18° to 27° vs. 36° to 45°) and P=0.01 (18° to 27° vs. 45° to 54°)]. Conclusion: We hypothesize environmental pollution and mental stress due to the increased population size may be the main factors underlying differences in the sperm quality of men in northern and southern China.

Vacuum-Deposited Inorganic Perovskite Light-Emitting Diodes with External Quantum Efficiency Exceeding 10% via Composition and Crystallinity Manipulation of Emission Layer under High Vacuum.

Although vacuum-deposited metal halide perovskite light-emitting diodes (PeLEDs) have great promise for use in large-area high-color-gamut displays, the efficiency of vacuum-sublimed PeLEDs currently lags that of solution-processed counterparts. In this study, highly efficient vacuum-deposited PeLEDs are prepared through a process of optimizing the stoichiometric ratio of the sublimed precursors under high vacuum and incorporating ultrathin under- and upper-layers for the perovskite emission layer (EML). In contrast to the situation in most vacuum-deposited organic light-emitting devices, the properties of these perovskite EMLs are highly influenced by the presence and nature of the upper- and presublimed materials, thereby allowing us to enhance the performance of the resulting devices. By eliminating Pb° formation and passivating defects in the perovskite EMLs, the PeLEDs achieve an outstanding external quantum efficiency (EQE) of 10.9% when applying a very smooth and flat geometry; it reaches an extraordinarily high value of 21.1% when integrating a light out-coupling structure, breaking through the 10% EQE milestone of vacuum-deposited PeLEDs.

Harnessing 2D Ruddlesden-Popper Perovskite with Polar Organic Cation for Ultrasensitive Multibit Nonvolatile Transistor-Type Photomemristors.

Photomemristors have been regarded as one of the most promising candidates for next-generation hardware-based neuromorphic computing due to their potentials of fast data transmission and low power consumption. However, intriguingly, so far, photomemristors seldom display truly nonvolatile memory characteristics with high light sensitivity. Herein, we demonstrate ultrasensitive photomemristors utilizing two-dimensional (2D) Ruddlesden-Popper (RP) perovskites with a highly polar donor-acceptor-type push-pull organic cation, 4-(5-(2-aminoethyl)thiophen-2-yl)benzonitrile+ (EATPCN+), as charge-trapping layers. High linearity and almost zero-decay retention are observed in (EATPCN)2PbI4 devices, which are very distinct from that of the traditional 2D RP perovskite devices consisting of nonpolar organic cations, such as phenethylamine+ (PEA+) and octylamine+ (OA+), and traditional 3D perovskite devices consisting of methylamine+ (MA+). The 2-fold advantages, including desirable spatial crystal arrangement and engineered energetic band alignment, clarify the mechanism of superior performance in (EATPCN)2PbI4 devices. The optimized (EATPCN)2PbI4 photomemristor also shows a memory window of 87.9 V and an on/off ratio of 106 with a retention time of at least 2.4 × 105 s and remains unchanged after >105 writing-reading-erasing-reading endurance cycles. Very low energy consumptions of 1.12 and 6 fJ for both light stimulation and the reading process of each status update are also demonstrated. The extremely low power consumption and high photoresponsivity were simultaneously achieved. The high photosensitivity surpasses that of a state-of-the-art commercial pulse energy meter by several orders of magnitude. With their outstanding linearity and retention, rabbit images have been rebuilt by (EATPCN)2PbI4 photomemristors, which truthfully render the image without fading over time. Finally, by utilizing the powerful ∼8 bits of nonvolatile potentiation and depression levels of (EATPCN)2PbI4 photomemristors, the accuracies of the recognition tasks of CIFAR-10 image classification and MNIST handwritten digit classification have reached 89% and 94.8%, respectively. This study represents the first report of utilizing a functional donor-acceptor type of organic cation in 2D RP perovskites for high-performance photomemristors with characteristics that are not found in current halide perovskites.

All-Vacuum-Deposited Perovskite X-ray Detector with a Record-High Self-Powered Sensitivity of 1.2 C Gy-1 cm-3.

Highly sensitive X-ray detection is crucial in, for example, medical imaging and secure inspection. Halide perovskite X-ray detectors are promising candidates for detecting highly energetic radiation. In this report, we describe vacuum-deposited Cs-based perovskite X-ray detectors possessing a p-i-n architecture. Because of the built-in potential of the p-i-n structure, these perovskite X-ray detectors were capable of efficient charge collection and displayed an exceptionally high X-ray sensitivity (1.2 C Gyair-1 cm-3) under self-powered, zero-bias conditions. We ascribe the outstanding X-ray sensitivity of the vacuum-deposited CsPbI2Br devices to their prominent charge carrier mobility. Moreover, these devices functioned with a lowest detection limit of 25.69 nGyair s-1 and possessed excellent stability after exposure to over 3000 times the total dose of a chest X-ray image. For comparison, we also prepared traditional spin-coated CH3NH3-based perovskite devices having a similar device architecture. Their volume sensitivity was only one-fifth of that of the vacuum-deposited CsPbI2Br devices. Thus, all-vacuum deposition appears to be a new strategy for developing perovskite X-ray detectors; with a high practical deposition rate, a balance can be reached between the thickness of the absorbing layer and the fabrication time.

Room-Temperature Fabricated Multilevel Nonvolatile Lead-Free Cesium Halide Memristors for Reconfigurable In-Memory Computing.

Recently, conductive-bridging memristors based on metal halides, such as halide perovskites, have been demonstrated as promising components for brain-inspired hardware-based neuromorphic computing. However, realizing devices that simultaneously fulfill all of the key merits (low operating voltage, high dynamic range, multilevel nonvolatile storage capability, and good endurance) remains a great challenge. Herein, we describe lead-free cesium halide memristors incorporating a MoOX interfacial layer as a type of conductive-bridging memristor. With this design, we obtained highly uniform and reproducible memristors that exhibited all-around resistive switching characteristics: ultralow operating voltages (<0.18 V), low variations (<30 mV), long retention times (>106 s), high endurance (>105, full on/off cycles), record-high on/off ratios (>1010, smaller devices having areas <5 × 10-4 mm2), fast switching (<200 ns), and multilevel programming abilities (>64 states). With these memristors, we successfully implemented stateful logic functions in a reconfigurable architecture and accomplished a high classification accuracy (ca. 90%) in the simulated hand-written-digits classification task, suggesting their versatility in future in-memory computing applications. In addition, we exploited the room-temperature fabrication of the devices to construct a fully functional three-dimensional stack of memristors, which demonstrates their potential of high-density integration desired for data-intensive neuromorphic computing. High-performance, environmentally friendly cesium halide memristors provide opportunities toward next-generation electronics beyond von Neumann architectures.

Sperm retrieval rates and clinical outcomes for patients with different causes of azoospermia who undergo microdissection testicular sperm extraction-intracytoplasmic sperm injection.

The aim of our study was to compare the sperm retrieval rates (SRRs) and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI). We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI. Patients with azoospermia were classified into Group A (Klinefelter syndrome, n = 284, 125 cycles), Group B (azoospermia Y chromosome factor c [AZFc] microdeletion, n = 91, 64 cycles), Group C (cryptorchidism, n = 52, 39 cycles), Group D (previous mumps and bilateral orchitis, n = 23, 23 cycles), and Group E (idiopathic azoospermia, n = 319, 96 cycles). Clinical characteristics, SRR, embryonic development, and pregnancy outcomes of the patients were compared between all groups. Patients in Group D had the highest and most successful SRR. The average SRR for all patients was 46.0%. The rates of clinical pregnancy, implantation, and live birth in Group D were 78.3%, 65.0%, and 74.0%, respectively, which were higher than those in all other groups (P < 0.05). Group B patients had the lowest clinical pregnancy, implantation, and live birth rates of all groups (P < 0.05). No differences were found in the miscarriage rate or birth defects among the groups (P > 0.05). Patients with orchitis had the highest SRR and best clinical outcomes. Although AZFc microdeletion patients had a higher SRR, their clinical outcomes were worse.

Clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection with fresh or cryopreserved sperm in patients with nonobstructive azoospermia.

We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI) treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia (NOA). A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles (Group A). Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles (Group B). We compared patient characteristics, embryonic development, and pregnancy outcomes between Groups A and B. There was no statistical difference in the patient characteristics, and no differences were observed with fertilization or quality embryo rates between Groups A and B. The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B (both P < 0.05). In conclusion, fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.