Peptide derived from RAGE efficiently improves oocyte development through attenuating oxidative stress in oocytes of mice with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder in reproductive-aged women that frequently leads to infertility due to poor oocyte quality. In this study, we identified a new active peptide (advanced glycation end products receptors RAGE344-355 ) from PCOS follicular fluid using mass spectrometry. We found that supplementing PCOS-like mouse oocytes with RAGE344-355 attenuated both meiotic defects and oxidative stress levels, ultimately preventing developmental defects. Additionally, our results suggest that RAGE344-355 may interact with eEF1a1 to mitigate oxidative meiotic defects in PCOS-like mouse oocytes. These findings highlight the potential for further clinical development of RAGE344-355 as a potent supplement and therapeutic option for women with PCOS. This research addresses an important clinical problem and offers promising opportunities for improving oocyte quality in PCOS patients.

Human defensin-inspired discovery of peptidomimetic antibiotics.

SignificanceWe report the development of peptidomimetic antibiotics derived from a natural antimicrobial peptide, human α-defensin 5. By engaging multiple bacterial targets, the lead compound is efficacious in vitro and in vivo against bacteria with highly inducible antibiotic resistance, promising a useful therapeutic agent for the treatment of infections caused by antibiotic-resistant bacteria.

Miniature two-photon microscopy for enlarged field-of-view, multi-plane and long-term brain imaging.

We have developed a miniature two-photon microscope equipped with an axial scanning mechanism and a long-working-distance miniature objective to enable multi-plane imaging over a volume of 420 × 420 × 180 µm3 at a lateral resolution of ~1 µm. Together with the detachable design that permits long-term recurring imaging, our miniature two-photon microscope can help decipher neuronal mechanisms in freely behaving animals.

The novel peptide PFAP1 promotes primordial follicle activation by binding to MCM5.

Premature ovarian failure (POF) is a complication of ovarian dysfunction resulting from the depletion or dysfunction of primordial follicles (PFs) in the ovaries. However, residual follicles that have the potential to be activated are present in POF or aged women. Little is known about the mechanisms by which the remaining dormant PFs in POF patients are activated. Using mass spectrometry, we screened differentially generated peptides extracted from the ovarian cortical tissue biopsies of patients with or without POF, during which we identified PFAP1, a peptide that significantly promoted the activation of PFs in the ovaries of 3 dpp mice in vitro. PFAP1 reversed age-related fertility damage in vivo to a certain extent, promoted estrogen (E2) and anti-mullerian hormone (AMH) production (p < .05), and decreased the levels of follicle-stimulating hormone (FSH) (p < .05). In newborn mouse ovaries, PFAP1 could bind to the protein minichromosome maintenance protein 5 (MCM5) and inhibit its ubiquitination and degradation. In addition, PFAP1 promoted the proliferation of GCs, probably by regulating the function and production of MCM5. In conclusion, PFAP1 could promote the activation of PFs in the ovaries of newborn mice, partially restore the ovarian function of aged mice, and increase the proliferation of primary granulosa cells (GCs) by regulating the function of MCM5. PFAP1 is a promising novel peptide that may be developed into a new therapeutic agent for POF and other ovarian diseases.

R-spondin-1 induces Axin degradation via the LRP6-CK1ε axis.

R-spondins (RSPOs) are secreted signaling molecules that potentiate the Wnt/ß-catenin pathway by cooperating with Wnt ligands. RSPO1 is crucial in tissue development and tissue homeostasis. However, the molecular mechanism by which RSPOs activate Wnt/ß-catenin signaling remains elusive. In this study, we found that RSPOs could mediate the degradation of Axin through the ubiquitin-proteasome pathway. The results of Co-IP showed that the recombinant RSPO1 protein promoted the interaction between Axin1 and CK1ε. Either knockout of the CK1ε gene or treatment with the CK1δ/CK1ε inhibitor SR3029 caused an increase in Axin1 protein levels and attenuated RSPO1-induced degradation of the Axin1 protein. Moreover, we observed an increase in the number of associations of LRP6 with CK1ε and Axin1 following RSPO1 stimulation. Overexpression of LRP6 further potentiated Axin1 degradation mediated by RSPO1 or CK1ε. In addition, recombinant RSPO1 and Wnt3A proteins synergistically downregulated the protein expression of Axin1 and enhanced the transcriptional activity of the SuperTOPFlash reporter. Taken together, these results uncover the novel mechanism by which RSPOs activate Wnt/ß-catenin signaling through LRP6/CK1ε-mediated degradation of Axin.

Food insecurity is related to eating disorder psychopathology beyond psychological distress in rural Chinese adolescents.

OBJECTIVE: This study aimed to examine the relationship between food insecurity (FI) and eating disorder psychopathology in a large sample of rural Chinese adolescents. METHODS: Analyses included 1654 adolescents (55.4% girls; Mage = 16.54 years, SD = 1.45) from a rural high school in southwestern China. FI, eating disorder psychopathology, and psychological distress (i.e., symptoms of depression, anxiety, and stress) were assessed. Data were analyzed by sex. Pearson correlation analysis was performed to investigate the zero-order association between FI and eating disorder psychopathology. Hierarchical linear regressions were used to explore whether FI could explain meaningful variance in eating disorder psychopathology beyond psychological distress and demographic covariates (e.g., socioeconomic status). RESULTS: FI was significantly associated with higher eating disorder psychopathology for boys (r = 0.44, p < 0.001) and girls (r = 0.43, p < 0.001), with medium-to-large effect sizes. FI accounted for significant unique variance in eating disorder psychopathology beyond psychological distress and demographic covariates for boys (ΔR2 = 0.14, p < 0.001) and girls (ΔR2 = 0.10, p < 0.001). DISCUSSION: Using a large sample of rural Chinese adolescents, this study extends the connection between FI and eating disorder pathology in adolescents beyond the Western context. Future investigations on the mechanisms underlying FI and eating disorder psychopathology are warranted for developing prevention strategies for eating disorders among rural Chinese adolescents. PUBLIC SIGNIFICANCE: This is the first investigation that examined the link between FI and eating disorder psychopathology among rural Chinese adolescents. Our findings highlight the importance of incorporating FI as a potential risk factor to screen for the prevention and intervention of eating disorders among rural Chinese adolescents.

Atomic Level-Macroscopic Structure-Activity of Inhomogeneous Localized Aggregates Enabled Ultra-Low Temperature Hybrid Aqueous Batteries.

The utilization of hybrid aqueous electrolytes has significantly broadened the electrochemical and temperature ranges of aqueous batteries, such as aqueous zinc and lithium-ion batteries, but the design principles for extreme operating conditions remain poorly understood. Here, we systematically unveil the ternary interaction involving salt-water-organic co-solvents and its intricate impacts on both the atomic-level and macroscopic structural features of the hybrid electrolytes. This highlights a distinct category of micelle-like structure electrolytes featuring organic-enriched phases and nanosized aqueous electrolyte aggregates, enabled by appropriate low donor number co-solvents and amphiphilic anions. Remarkably, the electrolyte enables exceptional high solubility, accommodating up to 29.8 m zinc triflate within aqueous micelles. This configuration maintains an intra-micellar salt-in-water setup, allowing for a broad electrochemical window (up to 3.86 V), low viscosity, and state-of-the-art ultralow-temperature zinc ion conductivity (1.58 mS cm-1 at -80°C). Building upon the unique nature of the inhomogeneous localized aggregates, this micelle-like electrolyte facilitates dendrite-free Zn plating/stripping, even at -80°C. The assembled Zn||PANI battery showcases an impressive capacity of 71.8 mAh g-1 and an extended lifespan of over 3000 cycles at -80°C. This study opens up a promising approach in electrolyte design that transcends conventional local atomic solvation structures, broadening the water-in-salt electrolyte concept.

Biomechanical Comparison of 3 Thumb Ulnar Collateral Ligament Repair Methods.

PURPOSE: Differences in range of motion, pinch strength, biomechanical strength, or joint angulation have previously been investigated for various means of treatment of ulnar collateral ligament (UCL) tears. We sought to address a gap in the literature by comparing thumb metacarpophalangeal (MCP) joint angle measurements and biomechanical strength before complete, acute UCL tear and after repair with suture anchors (SA), suture tape (ST) anchor augmentation, or reconstruction with palmaris longus graft (PL). METHODS: Thumbs and, if present, the PL tendon were harvested from 15 fresh-frozen cadavers. Each thumb specimen was secured into a servohydraulic biomechanical testing frame to evaluate native radiographic MCP joint angles at 0° flexion when loaded with 0, 5, and 13 N of radial force. Subsequently, a single hand surgeon (S.M.K.) performed complete transection and UCL repair via 1 of 3 methods: SA (n = 5), ST (n = 5), or reconstruction with PL (n = 5). Following repair, MCP joint angles were radiographically evaluated. Specimens that did not fail during joint angle testing were transferred to a separate testing frame for load-to-failure testing. Angle measurements and mean load-to-failure were compared between the groups, and angulation was also compared with each group's native control. RESULTS: Both ST and SA groups demonstrated comparable stiffness to their native controls, whereas the PL group was significantly more lax. The ST repair was significantly stiffer than the other constructs. ST also required higher forces to reach failure compared to both SA and PL. No difference was found between SA and PL groups. CONCLUSIONS: Although both ST and SA constructs recapitulate native joint stiffness, repair with ST demonstrated the greatest biomechanical strength in stiffness and load-to-failure. CLINICAL RELEVANCE: For complete, acute tears of the thumb UCL, ST may be superior for maintaining MCP joint stability and strength over SA and PL.

Predicting the risk of acute kidney injury after cardiopulmonary bypass: development and assessment of a new predictive nomogram.

BACKGROUND: Acute kidney injury (AKI) is a common and severe complication of cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to establish a model to predict the probability of postoperative AKI in patients undergoing cardiac surgery with CPB. METHODS: We conducted a retrospective, multicenter study to analyze 1082 patients undergoing cardiac surgery under CPB. The least absolute shrinkage and selection operator regression model was used to optimize feature selection for the AKI model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the feature selected in the previously mentioned model. Finally, we used multiple methods to evaluate the accuracy and clinical applicability of the model. RESULTS: Age, gender, hypertension, CPB duration, intraoperative 5% bicarbonate solution and red blood cell transfusion, urine volume were identified as important factors. Then, these risk factors were created into nomogram to predict the incidence of AKI after cardiac surgery under CPB. CONCLUSION: We developed a nomogram to predict the incidence of AKI after cardiac surgery. This model can be used as a reference tool for evaluating early medical intervention to prevent postoperative AKI.

High-energy high-dose microfocus X-ray computed tomography driven by high-average-current photo-injector.

High-energy, high-dose, microfocus X-ray computed tomography (HHM CT) is one of the most effective methods for high-resolution X-ray radiography inspection of high-density samples with fine structures. Minimizing the effective focal spot size of the X-ray source can significantly improve the spatial resolution and the quality of the sample images, which is critical and important for the performance of HHM CT. The objective of this study is to present a 9 MeV HHM CT prototype based on a high-average-current photo-injector in which X-rays with about 70µm focal spot size are produced via using tightly focused electron beams with 65/66µm beam size to hit an optimized tungsten target. In digital radiography (DR) experiment using this HHM CT, clear imaging of a standard 0.1 mm lead DR resolution phantom reveals a resolution of 6 lp/mm (line pairs per mm), while a 5 lp/mm resolution is obtained in CT mode using another resolution phantom made of 10 mm ferrum. Moreover, comparing with the common CT systems, a better turbine blade prototype image was obtained with this HHM CT system, which also indicates the promising application potentials of HHM CT in non-destructive inspection or testing for high-density fine-structure samples.

The top 50 most cited articles in both-bone forearm open reduction internal fixation in the skeletally mature patient.

PURPOSE: Both-bone forearm fractures in the adult population frequently and usually necessitate an operative reduction. The purpose of this study was to identify the 50 most cited publications regarding both-bone ORIF and evaluates their level of evidence to help guide the best treatment and management practices, as well as gauge the current level of inquiry into this topic. METHODS: The Clarivate Analytics Web of Knowledge Database was queried. The top 50 most cited articles identified as relevant were analyzed. Aggregate citation counts, citation density, type of study, and level of evidence were documented for each of the 50 articles. Abstracts from the last decade of prominent orthopaedic meetings were analyzed to determine the current level of inquiry into this area. RESULTS: The initial search yielded 408 results. There were 27 articles published before 2000 and 23 after. The total summation of citations for the top 50 articles totaled 2062. Each study was classified according to its study design and level of evidence. The most common was case series (34). Level IV studies were most numerous (34). Since 2010, the subject of both-bone forearm fracture ORIF was presented 8 times at prominent orthopaedic conferences. CONCLUSION: Our work demonstrated 54% of top-50 studies are pre-2000 and the majority are Level IV evidence. Additionally, despite the established treatment, there is active inquiry into this topic. Higher quality research can be helpful to validify treatment and management options.

Chromosomal instability during neurogenesis in Huntington's disease.

Huntington's disease (HD) is a fatal neurodegenerative disease caused by expansion of CAG repeats in the Huntingtin gene (HTT). Neither its pathogenic mechanisms nor the normal functions of HTT are well understood. To model HD in humans, we engineered a genetic allelic series of isogenic human embryonic stem cell (hESC) lines with graded increases in CAG repeat length. Neural differentiation of these lines unveiled a novel developmental HD phenotype: the appearance of giant multinucleated telencephalic neurons at an abundance directly proportional to CAG repeat length, generated by a chromosomal instability and failed cytokinesis over multiple rounds of DNA replication. We conclude that disrupted neurogenesis during development is an important, unrecognized aspect of HD pathogenesis. To address the function of normal HTT protein we generated HTT+/- and HTT-/- lines. Surprisingly, the same phenotype emerged in HTT-/- but not HTT+/- lines. We conclude that HD is a developmental disorder characterized by chromosomal instability that impairs neurogenesis, and that HD represents a genetic dominant-negative loss of function, contrary to the prevalent gain-of-toxic-function hypothesis. The consequences of developmental alterations should be considered as a new target for HD therapies.

Current mechanisms of primordial follicle activation and new strategies for fertility preservation.

Premature ovarian insufficiency (POI) is characterized by symptoms caused by ovarian dysfunction in patients aged <40 years. It is associated with a shortened reproductive lifespan. The only effective treatment for patients who are eager to become pregnant is IVF/Embryo Transfer (ET) using oocytes donated by young women. However, the use of the technique is constrained by the limited supply of oocytes and ethical issues. Some patients with POI still have some residual follicles in the ovarian cortex, which are not regulated by gonadotropin. These follicles are dormant. Therefore, activating dormant primordial follicles (PFs) to obtain high-quality oocytes for assisted reproductive technology may bring new hope for patients with POI. Therefore, this study aimed to explore the factors related to PF activation, such as the intercellular signaling network, the internal microenvironment of the ovary and the environment of the organism. In addition, we discussed new strategies for fertility preservation, such as in vitro activation and stem cell transplantation.

Investigation of combining-efficiency loss induced by a diffractive optical element in a single-aperture coherent beam combining system.

Filled-aperture geometries can be obtained using a diffractive optical element (DOE) in the coherent beam combining (CBC) architecture. Minimizing the beam deviation is crucial to maintain single-aperture output and reduce the combining-efficiency losses. In this study, we developed a theoretical model for investigating the combining-efficiency losses with beam deviation in a DOE-based CBC architecture. The beam deviations induced by the DOE-mount-tilt error, emitter-incident angular error, and DOE-groove-tilt error are discussed theoretically in detail and verified experimentally. The combining-efficiency losses caused by the three error sources are calculated. Meanwhile, the combining-efficiency losses affected by the beam size and the DOE period are analyzed. For an 11-channel CBC architecture with a DOE period of 50 µm and a beam size of 30 mm, the maximum combining-efficiency losses caused by the three error sources were 3.2%, 1.87%, and 36.41%, respectively, whereas those in case of a DOE period of 20 µm and a beam size of 10 mm were 14.34%, 8.58%, and 25.29%, respectively. We found that the combining-efficiency loss is most sensitive to the DOE-groove-tilt error.

Broadband thin-film and metamaterial absorbers using refractory vanadium nitride and their thermal stability.

Strong absorption of the full spectrum of sunlight at high temperatures is desired for photothermal devices and thermophotovoltaics. Here, we experimentally demonstrate a thin-film broadband absorber consisting of a vanadium nitride (VN) film and a SiO2 anti-reflective layer. Owing to the intrinsic high loss of VN, the fabricated absorber exhibits high absorption over 90% in the wide range of 400-1360 nm. To further enhance the near-infrared absorption, we also propose a metamaterial absorber by depositing patterned VN square patches on the thin-film absorber. An average absorption of 90.4% over the range of 400-2500 nm is achieved due to the excitation of broad electric dipole resonance. Both thin-film and metamaterial absorbers are demonstrated to possess excellent incident angle tolerances (up to 60°) and superior thermal stability at 800 ℃. The proposed refractory VN absorbers may be potentially used for solar energy harvesting, thermal emission, and photodetection.

Instantaneous response and suppression of SBS process in a short fiber system with binary sequence phase modulation.

We study the instantaneous response of stimulated Brillouin scattering (SBS) in a fiber system phase modulated by a binary sequence waveform. The buildup time constant of SBS kinetics is investigated analytically and experimentally. A series of binary sequences with adjustable dwell time and sequence period is constructed in order to examine both buildup and suppressing processes for SBS in 15 m short fiber. For a fiber system with SBS buildup time constant within several nanoseconds, the Stokes intensity can be effectively suppressed by implementing a binary sequence phase modulation with a dwell time close to or even less than the buildup time constant. Stokes intensity can be suppressed in several sequence periods, which exhibit a damped-oscillation-like trend.

Trichromatic and Tripolarization-Channel Holography with Noninterleaved Dielectric Metasurface.

Metasurfaces hold great potentials for advanced holographic display with extraordinary information capacity and pixel sizes in an ultrathin flat profile. A dual-polarization channel to encode two independent phase profiles or spatially multiplexed meta-holography by interleaved metasurfaces are captivated popular solutions to projecting multiplexed and vectorial images. However, the intrinsic limit of orthogonal polarization-channels, their crosstalk due to coupling between meta-atoms, and interleaving-induced degradation of efficiency and reconstructed image quality set great barriers for sophisticated meta-holography from being widely adopted. Here we report a noninterleaved TiO2 metasurface holography, and three distinct phase profiles are encoded into three orthogonal polarization bases with almost zero crosstalk. The corresponding three independently constructed intensity profiles are therefore assigned to trichromatic (RGB) beams, resulting in high-quality and high-efficiency vectorial meta-holography in the whole visible regime. Our strategy presents an unconventionally advanced holographic scheme by synergizing trichromatic colors and tripolarization channels, simply realized with a minimalist noninterleaved metasurface. Our work unlocks the metasurface's potentials on massive information storage, polarization optics, polarimetric imaging, holographic data encryption, etc.

Simulation and experimental study of laser-induced thermal deformation of spectral beam combination grating.

The multilayer dielectric (MLD) grating is a critical device for combining multiple laser beams into a single beam in a spectral beam combining (SBC) system. We established a theoretical thermal deformation model of the laser-irradiated MLD grating. Thermal deformation on the surface of the grating is simulated according to a series of parameters including the laser irradiation time, laser power density, and substrate size. To verify the model, we exposed a 960 l/mm, 50×50×1.5 mm3 grating to a laser power density of 3.61 kW/cm2 and observed the temperature change. We used a Twyman-Green interferometer to measure the interference fringes on the grating surface. Based on the Fourier-transform method and a Zernike polynomial fitting method, the real-time grating surface profile is reconstructed. The results show that substrate thickness increase or area decrease can reduce thermal deformation, the average decreases are 18.3% and 19.9%, respectively. The discussion and analysis of the grating thermal deformation are potentially valuable for designing grating to decrease the thermal deformation and improve the combined beam quality of a SBC system.

TREM2 regulates obesity-induced insulin resistance via adipose tissue remodeling in mice of high-fat feeding.

BACKGROUND: Adipose tissue remodeling plays a significant role in obesity-induced insulin resistance. Published studies reported that level of trigger receptor expressed on myeloid cells 2 (TREM2) in adipose tissue is up-regulated in animal models of obesity. This study aims to investigate whether TREM2 regulates obesity-induced insulin resistance via modulating adipose tissue remodeling in mice of high-fat diet (HFD). METHODS: Wild-type (WT) and TREM2-/- mice were both fed with a controlled-fat diet (CFD) or HFD for 12 weeks and studied for obesity and insulin resistance. Meanwhile, epididymal adipose tissue (EAT) was examined for morphological and pathological changes to determine adipose tissue remodeling. After that, adipocyte-derived MCP-1 was measured in adipocytes, adipose tissue and circulation. Next, inflammatory cytokines were determined in adipose tissue macrophages (ATM). At last, livers were analyzed for hepatic steatosis. RESULTS: TREM2-/- mice on HFD had increased obesity and insulin resistance compared with WT counterparts. Adipose tissue from TREM2-/- mice exhibited reduced mass but greater adipocyte hypertrophy and increased adipocyte death. Besides, adipocyte-derived MCP-1 was down-regulated in TREM2-/- mice, and circulating MCP-1 level was lower than that of WT mice. Furthermore, TREM2-/- mice displayed reduced infiltration of F4/80+CD11c+ macrophages into adipose tissue, which was unable to form crown-like structures (CLS) to clean dead adipocytes and cellular contents. Also, TREM2 deficiency augmented inflammatory response of adipose tissue macrophages in HFD mice. In addition, TREM2-/- mice demonstrated more severe hepatic steatosis than WT counterparts under HFD feeding. CONCLUSIONS: Trigger receptor expressed on myeloid cells 2 may function as a feedback mechanism to curb obesity-induced insulin resistance via regulating adipose tissue remodeling.