USP11 regulates proliferation and apoptosis of human spermatogonial stem cells via HOXC5-mediated canonical WNT/ß-catenin signaling pathway.

Spermatogonial stem cells (SSCs) are capable of transmitting genetic information to the next generations and they are the initial cells for spermatogenesis. Nevertheless, it remains largely unknown about key genes and signaling pathways that regulate fate determinations of human SSCs and male infertility. In this study, we explored the expression, function, and mechanism of USP11 in controlling the proliferation and apoptosis of human SSCs as well as the association between its abnormality and azoospermia. We found that USP11 was predominantly expressed in human SSCs as shown by database analysis and immunohistochemistry. USP11 silencing led to decreases in proliferation and DNA synthesis and an enhancement in apoptosis of human SSCs. RNA-sequencing identified HOXC5 as a target of USP11 in human SSCs. Double immunofluorescence, Co-immunoprecipitation (Co-IP), and molecular docking demonstrated an interaction between USP11 and HOXC5 in human SSCs. HOXC5 knockdown suppressed the growth of human SSCs and increased apoptosis via the classical WNT/ß-catenin pathway. In contrast, HOXC5 overexpression reversed the effect of proliferation and apoptosis induced by USP11 silencing. Significantly, lower levels of USP11 expression were observed in the testicular tissues of patients with spermatogenic disorders. Collectively, these results implicate that USP11 regulates the fate decisions of human SSCs through the HOXC5/WNT/ß-catenin pathway. This study thus provides novel insights into understanding molecular mechanisms underlying human spermatogenesis and the etiology of azoospermia and it offers new targets for gene therapy of male infertility.

[Micro-energy medicine in the treatment of erectile dysfunction: An update].

Erectile dysfunction (ED) is one of the most common sexual disorders in males, which seriously affects the health of the patient and well-being of the family. The therapeutic strategy of ED is an individualized comprehensive treatment based on phosphodiesterase inhibitors. At present, as a new option for the treatment of ED, micro-energy medicine has attracted more and more attention in its therapeutic effects and advantages. This article presents an overview of the progress in the studies of micro-energy medicine in the treatment of ED.

Enhanced optoelectronic reservoir computation using semiconductor laser with double delay feedbacks.

We numerically explored the enhanced performance and physical mechanism of semiconductor laser (SL) based reservoir computation (RC) with double optoelectronic feedback (DOEF). One-step and multistep Santa Fe time series predictions were used as standard test benchmarks in this work. We found that in the optimized parameter region the normalized mean square error (NMSE) of an SL-based RC under DOEF is smaller than an SL-based RC with single optoelectronic feedback (SOEF). In addition, the performance improvement is more obvious for multistep prediction, which is particularly suitable for more complex tasks that requires a higher memory capability (MC). The enriched node states (optical intensity of the virtual nodes for each sample) and the enhanced MC of the proposed DOEF were verified by a comparison to SOEF under the optimized feedback strength. The influence of the feedback strength and the delay difference on the NMSE and the MC was also investigated. Our study should be helpful in the design of a high-performance optoelectronic RC based on an SL.

Coatings on Lithium Battery Separators: A Strategy to Inhibit Lithium Dendrites Growth.

Lithium metal is considered a promising anode material for lithium secondary batteries by virtue of its ultra-high theoretical specific capacity, low redox potential, and low density, while the application of lithium is still challenging due to its high activity. Lithium metal easily reacts with the electrolyte during the cycling process, resulting in the continuous rupture and reconstruction of the formed SEI layer, which reduces the cycling reversibility. On the other hand, repeated lithium plating/stripping processes can lead to uncontrolled growth of lithium dendrites and a series of safety issues caused by short-circuiting of the battery. Currently, modification of the battery separator layer is a good strategy to inhibit lithium dendrite growth, which can improve the Coulombic efficiency in the cycle. This paper reviews the preparation, behavior, and mechanism of the modified coatings using metals, metal oxides, nitrides, and other materials on the separator to inhibit the formation of lithium dendrites and achieve better stable electrochemical cycles. Finally, further strategies to inhibit lithium dendrite growth are proposed.

The prognostic nutritional index predicts the biochemical recurrence of patients treated with robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: To evaluate the prognostic nutritional index (PNI) in predicting the biochemical recurrence (BCR) of patients treated with robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: The clinical data of 136 patients treated with RALP in the Department of Urology, The Third Xiangya Hospital of Central South University were retrospectively analyzed. The endpoint of observation was BCR. The area under the receiver operating characteristic (ROC) curve was evaluated to determine the optimal cutoff value of PNI. The correlation of the PNI with BCR was estimated using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: The optimal cutoff value of the PNI was 46.03 according to the ROC curve. (95% confidence interval: 0.604-0.805, Youden index = 0.401, sensitivity = 82.5%, specificity = 57.6%, p < 0.01). Multivariate Cox analysis showed that clinical staging, prostate-specific antigen, and PNI were independent prognostic factors for predicting BCR in patients treated with RALP. CONCLUSION: PNI is an independent prognostic factor for predicting BCR in patients treated with RALP. The incorporation of the PNI into risk assessments may provide additional prognostic information.

Towards fast sensing along ultralong BOTDA: flatness enhancement by utilizing injection-locked dual-bandwidth probe wave.

Brillouin optical time-domain analysis (BOTDA) using distributed Brillouin amplification (DBA) only requires a milliwatt-level pump to achieve a sensing range beyond 100 km, which provides a powerful tool for temperature/strain sensing. However, similar to the majority of other long-range BOTDAs, the state-of-the-art reports require > 1000 times average, severely restricting the sensing speed. The blind area over tens of kilometers caused by the nonuniform Brillouin response and parasitic amplitude modulation (AM) are crucial factors affecting the signal-to-noise ratio (SNR). Here, a comprehensive performance optimization and substantial enhancement for BOTDA sensors was presented by the direct demodulation of an injection-locked dual-bandwidth probe wave. Injection locking (IL) can completely eliminate the impact of AM noise; dual-bandwidth probe enables self-adaptive pulse loss compensation, thereby intensifying the SNR flatness along the ultralong fiber, and direct probe demodulation can overcome nonlocal effects and allows ∼19.7 dB enhancement of probe input power. Therefore, using only 100 times average, ∼148.3 km sensing, and ∼5 m spatial resolution were achieved with < ∼0.8 MHz standard deviation of Brillouin frequency shift (BFS) over a broad range (∼131.7 km). The reduction in averages was more than 10 times that of the reported majority of long-range BOTDAs. Such performances were achieved without using time-consuming or post-processing techniques, such as optical pulse coding and image denoising. Because this approach is compatible with optical chirp chain technique without frequency sweeping, fast acquisition (0.3 s) was also realized, which has the potential for fast sensing at 3.3 Hz along a ∼150 km fiber.

Boosting transparent electromagnetic interference shielding by multi-cavity resonances.

We propose a multi-cavity resonant architecture that is established by employing two opposing ultrathin silver-based films to form a Fabry-Pérot (F-P) cavity and inserting one or two metallic mesh layers in between. Compared with the single F-P cavity, the multi-cavity architecture with one metallic mesh layer experimentally exhibits a ∼37% improvement in the average shielding effectiveness and maintains a transmittance over 80% at 550 nm. A more significant improvement of ∼108% in shielding effectiveness (SE) can be achieved by inserting two metallic mesh layers. The proposed multi-cavity architecture provides a strategy for removal of the hindrance to transparent electromagnetic interference shielding.

Primary abdominal cocoon with cryptorchidism: a case report.

BACKGROUND: We report a rare case of primary abdominal cocoon with bilateral cryptorchidism. CASE PRESENTATION: The patient had a history of laparoscopic surgery for bilateral cryptorchidism 6 years earlier. He was admitted to the hospital again due to intestinal obstruction. Surgery was performed on the patient after the failure of conservative treatment. The patient was diagnosed with primary abdominal cocoon. Instead of the greater omentum, many cocoon-like tissues surrounding the bowel were seen during operation. Abdominal surgery can increase the risk of intestinal adhesion, which is one of the main causes of intestinal obstruction, especially in patients with abdominal cocoon. We hypothesize that the surgery 6 years earlier to address transabdominal bilateral cryptorchidism accelerated the patient's intestinal obstruction. CONCLUSION: This case implies that it is important for urologists to evaluate whether their patients exhibit abdominal cocoon before cryptorchidism surgery, to choose better surgical methods and reduce the risks of poor prognosis.

Horizontal Gene Transfer of Short-Chain Dehydrogenase Coding Genes Contribute to the Biofilm Formation and Pathogenicity on Mycobacterium grossiae sp. nov. PB739T (=DSM 104744T).

Mycobacterium grossiae sp. nov. of type strain PB739T is a Gram-positive acid-alcohol-fast rod-shaped bacterium, which was recently isolated from a 76-year-old male who suffered from a 1-year history of hemoptysis. This strain was described as novel species in Mycobacterium genus. In this study, its genome was completely sequenced by PacBio technology, analyzed, and compared with other selected complete genome sequences of Mycobacterium to elucidate the distinct pathogenic features of the strain. The genomic analysis revealed that the genome of PB739T consists of one circular DNA chromosome of 5,637,923 bp with a GC content of 70.48% and one plasmid of 43,679 bp with a GC content of 66.24%. The entire genome contains 5434 predicted coding genes, 48 tRNAs, and 6 rRNA genes. Genome and comparative genomics against M. grossiae SCH identified three tandem short-chain dehydrogenase (SDR) genes which only exist in PB739T. These three tandem SDR genes locate in a Genomic island which was identified by Island Viewer. These SDR genes were predicted to be horizontally transferred from a Streptomyces ancestor based on phylogeny. Analysis of the mutant ΔSDR confirmed the relationship between these tandem genes with biofilm and pathogenicity. This report will provide us with an extended understanding of M. grossiae at the genomic level and would be helpful for understanding the evolution of Mycobacterium genus.

Rack1 mediates tyrosine phosphorylation of Anxa2 by Src and promotes invasion and metastasis in drug-resistant breast cancer cells.

BACKGROUND: Acquirement of resistance is always associated with a highly aggressive phenotype of tumor cells. Recent studies have revealed that Annexin A2 (Anxa2) is a key protein that links drug resistance and cancer metastasis. A high level of Anxa2 in cancer tissues is correlated to a highly aggressive phenotype. Increased Anxa2 expression appears to be specific in many drug-resistant cancer cells. The functional activity of Anxa2 is regulated by tyrosine phosphorylation at the Tyr23 site. Nevertheless, the accurate molecular mechanisms underlying the regulation of Anxa2 tyrosine phosphorylation and whether phosphorylation is necessary for the enhanced invasive phenotype of drug-resistant cells remain unknown. METHODS: Small interfering RNAs, small molecule inhibitors, overexpression, loss of function or gain of function, rescue experiments, Western blot, wound healing assays, transwell assays, and in vivo metastasis mice models were used to investigate the functional effects of Rack1 and Src on the tyrosine phosphorylation of Anxa2 and the invasion and metastatic potential of drug-resistant breast cancer cells. The interaction among Rack1, Src, and Anxa2 in drug-resistant cells was verified by co-immunoprecipitation assay. RESULTS: We demonstrated that Anxa2 Tyr23 phosphorylation is necessary for multidrug-resistant breast cancer invasion and metastasis. Rack1 is required for the invasive and metastatic potential of drug-resistant breast cancer cells through modulating Anxa2 phosphorylation. We provided evidence that Rack1 acts as a signal hub and mediates the interaction between Src and Anxa2, thereby facilitating Anxa2 phosphorylation by Src kinase. CONCLUSIONS: Our findings suggest a convergence point role of Rack1/Src/Anxa2 complex in the crosstalk between drug resistance and cancer aggressiveness. The interaction between Anxa2 and Rack1/Src is responsible for the association between drug resistance and invasive/metastatic potential in breast cancer cells. Thus, our findings provide novel insights on the mechanism underlying the functional linkage between drug resistance and cancer aggressiveness.

Discovery of Nonpeptide, Reversible HER1/HER2 Dual-Targeting Small-Molecule Inhibitors as Near-Infrared Fluorescent Probes for Efficient Tumor Detection, Diagnostic Imaging, and Drug Screening.

The abnormal expression of epidermal growth factor receptors HER1(EGFR) and HER2 is strongly associated with cancer invasion, metastasis, and angiogenesis. Their molecular detection is mainly executed using genetically encoded or antibody-based diagnostic tracers, but no dual-targeting small-molecule bioprobe has been achieved. Here, we report the novel small-molecule fluorescent probes Cy3-AFTN and Cy5-AFTN as potent dual-targeting inhibitors for efficient detection of HER1/HER2 expression in cancer cells and in vivo tumor diagnostic imaging. Unlike the irreversible HER1/HER2 inhibitors, Cy3-AFTN and Cy5-AFTN were designed as reversible/noncovalent probes based on the clinical drug afatinib, by making the molecule structurally impossible for receptor-mediated Michael additions. The synthesized probes were validated with live cell fluorescence imaging, flow cytometry and confocal-mediated competitive binding inhibition, molecular docking study, and in vivo xenograft tumor detection. The probes are competitively replaceable by other HER1/HER2 inhibitors; thus, they are potentially useful in fluorometric high-throughput screening for drug discovery.

Ultraflexible Transparent Bio-Based Polymer Conductive Films Based on Ag Nanowires.

The unstable mechanical properties of flexible transparent conductive films (TCFs) make it difficult for them to meet the requirements for displays or wearable devices. Here, the relationship between the mechanism behind the bending behavior and the electrical properties, which is important for improving the mechanical stability of flexible TCFs, is explored. Flexible TCFs are reported based on silver nanowires (AgNWs) and bio-based poly(ethylene-co-1,4-cyclohexanedimethylene 2,5-furandicarboxylate)s (PECFs), with a low sheet resistance (23.8 Ω sq-1 at 84.6% transmittance) and superior mechanical properties. The electrical properties of the AgNW/PECFs composite film show almost no change after bending for 2000 times.

Complete Genome Sequence of Massilia oculi sp. nov. CCUG 43427T (=DSM 26321T), the Type Strain of M. oculi, and Comparison with Genome Sequences of Other Massilia Strains.

Massilia oculi sp. nov. of type strain CCUG 43427T is a Gram-negative, rod-shaped, nonspore-forming bacterium, which was recently isolated from the eye of a patient suffering from endophthalmitis and was described as novel species in Massilia genus. In this study, we present the complete genome sequence of this strain by using Pacbio SMRT cell platform and compare this sequence with the genomes of 30 Massilia representative strains. Also, a comprehensive search was conducted for genes and proteins involved in antibiotic resistance and pathogenicity. The genome of CCUG 43427T is 5,844,653 bp with 65.55% GC content. This genome contains four prophages and four genomic islands (GIs). The cobalt/zinc/cadmium transporter locus CzcABCD is included in these GIs. This GI was predicted to play important role in bacterial heavy-metal tolerance. The in silico genome analysis also revealed that this strain contains a lot of antibiotic resistance and pathogenicity related genes. This result suggested that this strain may has evolved a wide arsenal of weapons for pathogenicity and survival. Genome comparison among CCUG 43427T and other 30 Massilia strains revealed that more than 400 genes are unique in CCUG 43427T. Among these, one gene cluster, which was annotated to be important for LOS biosynthesis, catalytic mechanism and the substrate specificity of the enzyme, was predicted to be horizontally transferred by using phylogenies and biased GC content.

Tyr23 phosphorylation of Anxa2 enhances STAT3 activation and promotes proliferation and invasion of breast cancer cells.

PURPOSE: Overexpression of Annexin A2 (Anxa2) is positively correlated with breast cancer progression, drug resistance, and poor prognosis of patients with breast cancer. Tyr23 Phosphorylation by Src-family tyrosine kinase is an important post-translational modification of Anxa2. This modification regulates the subcellular localization and functions of Anxa2 and has significant effects on cell proliferation, migration, and invasion. This study aims at revealing the association of Anxa2-Tyr23 phosphorylation in Anxa2-mediated acceleration of breast cancer progression and their elaborate molecular mechanisms. METHODS: Cell biological function experiments were performed to determine the effects of Anxa2-Tyr23 Phosphorylation on breast cancer cell proliferation and invasion in vitro and metastasis in vivo. The interaction of Tyr23 phosphorylated Anxa2 and STAT3 was verified by co-immunoprecipitation assay. Related mRNA and protein expression levels of cyclin D1 and MMP2/9 and phosphorylation level of STAT3 were detected. RESULTS: Anxa2-Tyr23 phosphorylation is necessary for proliferation, invasion, and metastasis of breast cancer cells in vitro and in vivo. Tyr23 phosphorylated Anxa2 binds and enhances the sensitivity of STAT3 activation in response to IL-6, thereby increasing the protein and mRNA expression levels of cyclin D1 and MMP2/9 which are STAT3 key target genes and serve pivotal regulatory functions in cell proliferation and invasion, respectively. CONCLUSION: Our findings further confirmed the regulatory role of Anxa2 and revealed the direct relationship between Anxa2-Tyr23 phosphorylation and activation of STAT3. Moreover, this study provides novel insights into the function of Anxa2-Tyr23 phosphorylation in signal transduction for further understanding of the mechanism through which Anxa2 promotes the progression of breast cancer.

Anomalous dispersion engineering of co-sputtering Ag-AZO hybrids for antireflection coatings.

Conventional antireflection coatings (ARCs), including single- and multi-layer, bionic micro/nano, and gradient-index structures, often do not take anomalous dispersive materials into account, but normal dispersion and Rayleigh configuration, known as a step-down index profile, in which low refractive index (RI) materials are adjacent to incident media and the high RI ones, are located on substrates. We found that the anomalous dispersive materials could be good candidates for novel sub-100 nm ARCs, considering the ab-initio impedance matching designs. Engineering the anomalous dispersion of co-sputtering Ag-AZO hybrid materials, two types of ARCs were fabricated on silicon substrates: a 70 nm tri-layer reverse-Rayleigh and a 140 nm bi-layer Rayleigh for comparison. We observed that both exhibited the average reflectance of 5.46% and 1.49% at the wavelength range from 400 to 780 nm, respectively, and were much lower than that of bare silicon, 38.02%, where the underlying origin for the reverse-Rayleigh AR was discussed. The studies on the engineering and integration of anomalous dispersive materials into ARCs and optical elements would be of great significance for compact light harvesting, energy conversion, and radar stealth technology.

Silane Doping for Efficient Flexible Perovskite Solar Cells with Improved Defect Passivation and Device Stability.

In this work, doping 3-amino-propyl triethoxysilane (APTES) into a perovskite precursor is proven to be an effective strategy, which can passivate crystal defects, control the crystallization rate, and improve the morphology. APTES can form oligomers through hydrolysis and a condensation reaction, thus blocking the invasion of external water molecules. In addition, the lone pair electrons on the N atom in the amino group of APTES form a coordination bond with perovskite by sharing the empty 6p orbital on Pb2+, which can effectively passivate the defects of the film and realize a highly uniform and dense perovskite film with preferential crystal growth orientation. The film exhibits high (110) crystal plane orientation and long carrier lifetime and mobility, which improves the performance of flexible perovskite solar cells. Using this approach, the champion device presents an optimal power conversion efficiency of 19.84% with much promoted air stability. Moreover, the efficiency of flexible devices does not decrease after maximum power point irradiation for 360 s.

Research progress on the relationship between chronic prostatitis/chronic pelvic pain syndrome and the microbiota of the reproductive system.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common pelvic pain syndrome in males, seriously affecting patients' quality of life. For a long time, CP/CPPS has been considered a complex and variable disease, and its pathogenesis remains incompletely understood. Currently, CP/CPPS is believed to be a group of diseases characterized by pelvic pain or discomfort, urinary abnormalities, and other symptoms, each with its unique etiology, clinical characteristics, and outcomes, likely resulting from the action of pathogens or (and) certain non-infectious factors. Traditionally, CP/CPPS was thought to be unrelated to bacterial infections. However, in recent years, with the development of microbiology and the advancement of high-throughput sequencing technology, an increasing number of studies have suggested that microorganisms in the reproductive system may play an important role in the pathogenesis of CP/CPPS. The unique characteristics of CP/CPPS, such as its refractory nature and tendency to recur, may be closely related to the microbiota and their biological functions in the reproductive system. The relationship between CP/CPPS and reproductive system microorganisms is one of the current hot topics in microbiology and urology, receiving considerable attention from scholars in recent years and making a series of new advances. Through this review, we will comprehensively explore the relationship between CP/CPPS and reproductive system microorganisms, and look forward to future research directions, aiming to provide new ideas and methods for clinical diagnosis and treatment, thereby improving the treatment outcomes and quality of life of CP/CPPS patients.

A Fused-Ring Electron Acceptor with Phthalimide-Based Ending Groups for Efficient Ternary Organic Solar Cells.

The ternary strategy has been widely applied and recognized to be a valid strategy to enhance the organic photovoltaics' (OPVs) performance. Here, a new fused-ring electron acceptor, BTP-PIO, is designed and synthesized, whose ending groups were replaced by a phthalimide-based group (2-butylcyclopenta[f]isoindole-1,3,5,7(2H,6H)-tetraone) from traditional 2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile. The phthalimide-based ending groups endow BTP-PIO with the highest lowest unoccupied molecular orbital (LUMO) level and wider band gap than those of Y6. The ternary device based on PM6:Y6 with BTP-PIO as a guest electron acceptor achieved an elevated open-circuit voltage (VOC) of 0.848 V, a short-circuit current density (JSC) of 27.31 mA cm-2, and a fill factor (FF) of 73.9%, generating a remarkable power conversion efficiency (PCE) of 17.10%, which is superior to the PM6:Y6 binary device of 16.08%. The ternary device exhibited improved charge transfer, suppressed carrier recombination, and lower energy loss. BTP-PIO exhibited a good miscibility with Y6, and an alloy phase between BTP-PIO and Y6 was formed in the ternary bulk heterojunction, leading to better phase separation and molecular packing. This research reveals that ending group modification of Y6 derivatives is a feasible way to produce highly efficient ternary devices.

Efficient and stable semitransparent perovskite photovoltaics via a Lewis base incorporation.

Semitransparent perovskite solar cells (ST-PSCs) have great potential in building integrated photovoltaics. However, semitransparent devices suffer from a low electron mobility and an imbalanced charge-carrier transport, leading to an unsatisfactory power conversion efficiency (PCE) and limited stability. Herein, we report a high-performance ST-PSC via the incorporation of a special Lewis base. A better perovskite with an improved crystallinity and less defects was achieved, and a matched energy level alignment between the perovskite and [6,6]-phenyl-C61-butyric acid methyl ester was also induced, thereby leading to a high electron mobility and an exceptional balance of hole and electron mobility approaching 1 : 1. The prepared ST-PSC exhibited a PCE of 20.22% at average visible transmittance (AVT) of 4.93%, 18.32% at AVT of 14.38%, and 15.00% at AVT of 25.65%. These PCEs are the highest values among those ST-PSCs based on top metallic electrodes at a close AVT. The ST-PSCs maintained 92% of the initial PCE in storage for 1000 h, and they held 84% of the initial PCE under the continuous maximum power point tracking measurement for 530 hours. The work paves the way to realize ST-PSCs with a high PCE, high light utilization efficiency and substantially enhanced stability.

23.81%-Efficiency Flexible Inverted Perovskite Solar Cells with Enhanced Stability and Flexibility via a Lewis Base Passivation.

Lewis base molecules bind the undercoordinated lead atoms at interfaces and grain boundaries, leading to the high efficiency and stability of flexible perovskite solar cells (PSCs). We demonstrated a highly efficient, stable, and flexible PSC via interface passivation using a Lewis base of tri(o-tolyl)phosphine (TTP). It not only induced an intimate interface contact and a complete deposition of the perovskite thin layers on hole transport layers (HTLs) but also led to a better perovskite with a raised crystallinity, fewer defects, and a better morphology, including fewer gullies, high uniformity, and low roughness. Furthermore, the TTP treatments induced a good alignment of energy levels among the perovskites, HTLs, and C60. The resultant flexible inverted PSCs exhibited a high power conversion efficiency (PCE) of 23.81%, which is one of the highest PCEs among these flexible inverted PSCs. Moreover, the optimized flexible PSCs exhibited high storage stability, superior operation stability, and enhanced mechanical flexibility. This study presents an effective method to substantially raise the PCE, stability, and mechanical flexibility of the flexible inverted perovskite photovoltaics.