Prolonged Bacteroides pyogenes infection in a patient with multiple lung abscesses.

Bacteroides pyogenes is naturally found in the oral microbiome of cats and dogs and hence exposure, especially bites from these animals, is a major risk factor for human infections. B pyogenes is known to cause infections that persist despite antibiotic treatment and can have serious clinical outcomes. We present a novel case of complex lung abscesses associated with B pyogenes infection. A 55 year old man presents with a 3-month history of productive cough, night sweats, and 5 kg weight loss. An initial chest radiograph revealed mass-like opacities in the right upper lobe (RUL), right middle lobe (RML), and left lower lobe (LLL). Over the next 4 years the patient underwent multiple investigations and antimicrobial treatments until resolution of the abscesses. We believe that metronidazole in combination with moxifloxacin was a key component in the clinical cure of this patient.

Prevalence and confounders of chronic endometritis diagnosed using CD138 in patients with recurrent implantation failure.

Objective: This retrospective study aimed to investigate the prevalence of chronic endometritis, diagnosed using CD138 immunohistochemistry, among infertile women and to assess the association between chronic endometritis and recurrent implantation failure (RIF). Methods: In total, 266 patients who underwent hysteroscopy due to infertility between 2019 and 2020 were included in the analysis. Of these, 136 patients with RIF and 130 non-RIF patients were included in the study. CD138 immunohistochemistry test results, blood biomarkers (including natural killer cells, white blood cells, and the lymphocyte-to-neutrophil ratio), and data on pregnancy outcomes were obtained. If the CD138 test yielded a positive result, the patients received antibiotic treatment. Results: The overall proportion of CD138-positive patients was 32.7% (87/266). The CD138 positivity rate was not related to the number of cycles with implantation failure. In the RIF patient group, no significant associations were found between CD138 positivity and peripheral blood markers. The clinical pregnancy rates were similar between infertile women treated with antibiotics for chronic endometritis and those without chronic endometritis. Conclusion: To improve the pregnancy rate in infertile patients, it may be helpful to combine CD138 testing with other laboratory tests and administer antibiotic treatment if the result is positive.

Factors affecting the ongoing pregnancy rate in women with repeated implantation failure undergoing an endometrial receptivity array.

OBJECTIVE: In this retrospective study, we analyzed factors influencing the ongoing pregnancy rate (PR) in women with repeated implantation failure (RIF) undergoing embryo transfer with endometrial receptivity array (ERA). METHODS: Eighty-three consecutive personalized embryo transfers (pETs) with ERA, from 54 women with RIF, were selected from June 2020 to April 2022. Vitrified blastocyst transfer was timed based on ERA results. RESULTS: The ongoing PR per pET was 33.7%. Using ERA, the endometrium was identified as pre-receptive in 26 cycles, early receptive in 25 cycles, receptive in 31 cycles, and late receptive in one cycle. With cycles categorized into three receptivity phases (pre-receptive, early receptive, or receptive), no significant differences were found in the clinical PR (27.3%, 55.6%, and 40%, respectively) or ongoing PR (9.1%, 55.6%, and 40%, respectively) after a single blastocyst transfer. Similarly, no significant differences were observed in the clinical PR or ongoing PR after the transfer of two or more blastocysts. Among women with ongoing pregnancy relative to those without, age at first pET was significantly lower (35 years vs. 39 years, p=0.001), while blastocyst score (23 vs. 18, p=0.012) and the proportion of blastocyst scores >18 (71.4% vs. 38.9%, p=0.005) were significantly higher. In multiple logistic regression analysis, the woman's age (odds ratio [OR], 0.814; 95% confidence interval [CI], 0.706 to 0.940; p=0.005) and blastocyst score >18 (OR, 3.052; 95% CI, 1.075 to 8.665; p=0.036) were identified as significant factors influencing ongoing pregnancy. CONCLUSION: In pET with ERA, ongoing pregnancy was closely associated with woman's age and blastocyst quality.

Daam2 phosphorylation by CK2α negatively regulates Wnt activity during white matter development and injury.

Wnt signaling plays an essential role in developmental and regenerative myelination in the central nervous system. The Wnt signaling pathway is composed of multiple regulatory layers; thus, how these processes are coordinated to orchestrate oligodendrocyte (OL) development remains unclear. Here, we show CK2α, a Wnt/ß-catenin signaling Ser/Thr kinase, phosphorylates Daam2, inhibiting its function and Wnt activity during OL development. Intriguingly, we found Daam2 phosphorylation differentially impacts distinct stages of OL development, accelerating early differentiation followed by decelerating maturation and myelination. Application toward white matter injury revealed CK2α-mediated Daam2 phosphorylation plays a protective role for developmental and behavioral recovery after neonatal hypoxia, while promoting myelin repair following adult demyelination. Together, our findings identify a unique regulatory node in the Wnt pathway that regulates OL development via protein phosphorylation-induced signaling complex instability and highlights a new biological mechanism for myelin restoration.

Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation.

VLCFAs (very-long-chain fatty acids) are the most abundant fatty acids in myelin. Hence, during demyelination or aging, glia are exposed to higher levels of VLCFA than normal. We report that glia convert these VLCFA into sphingosine-1-phosphate (S1P) via a glial-specific S1P pathway. Excess S1P causes neuroinflammation, NF-κB activation, and macrophage infiltration into the CNS. Suppressing the function of S1P in fly glia or neurons, or administration of Fingolimod, an S1P receptor antagonist, strongly attenuates the phenotypes caused by excess VLCFAs. In contrast, elevating the VLCFA levels in glia and immune cells exacerbates these phenotypes. Elevated VLCFA and S1P are also toxic in vertebrates based on a mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Indeed, reducing VLCFA with bezafibrate ameliorates the phenotypes. Moreover, simultaneous use of bezafibrate and fingolimod synergizes to improve EAE, suggesting that lowering VLCFA and S1P is a treatment avenue for MS.

CK2α-dependent regulation of Wnt activity governs white matter development and repair.

Wnt signaling plays an essential role in developmental and regenerative myelination in the CNS. The Wnt signaling pathway is comprised of multiple regulatory layers; thus, how these processes are coordinated to orchestrate oligodendrocyte development remains unclear. Here we show CK2α, a Wnt/ß-catenin signaling Ser/Thr kinase, phosphorylates Daam2, inhibiting its function and Wnt-activity during oligodendrocyte development. Intriguingly, we found Daam2 phosphorylation differentially impacts distinct stages of oligodendrocyte development, accelerating early differentiation followed by decelerating maturation and myelination. Application towards white matter injury revealed CK2α-mediated Daam2 phosphorylation plays a protective role for developmental and behavioral recovery after neonatal hypoxia, while promoting myelin repair following adult demyelination. Together, our findings identify a novel regulatory node in the Wnt pathway that regulates oligodendrocyte development via protein phosphorylation-induced signaling complex instability and highlights a new biological mechanism for myelin restoration. Significance: Wnt signaling plays a vital role in OL development and has been implicated as an adverse event for myelin repair after white matter injury. Emerging studies have shed light on multi-modal roles of Wnt effectors in the OL lineage, but the underlying molecular mechanisms and modifiable targets in OL remyelination remain unclear. Using genetic mouse development and injury model systems, we delineate a novel stage-specific function of Daam2 in Wnt signaling and OL development via a S704/T7-5 phosphorylation mechanism, and determine a new role of the kinase CK2α in contributing to OL development. In-depth understanding of CK2α-Daam2 pathway regulation will allow us to precisely modulate its activity in conjunction with Wnt signaling and harness its biology for white matter pathology.

Astrocytic Slc4a4 regulates blood-brain barrier integrity in healthy and stroke brains via a NO-CCL2-CCR2 pathway.

Astrocytes play vital roles in blood-brain barrier (BBB) maintenance, yet how they support BBB integrity under normal or pathological conditions remains poorly defined. Recent evidence suggests pH homeostasis is a new cellular mechanism important for BBB integrity. In the current study, we investigated the function of an astrocyte-specific pH regulator, Slc4a4, in BBB maintenance and repair. We show that astrocytic Slc4a4 is required for normal astrocyte morphological complexity and BBB function. Multi-omics analyses identified increased astrocytic secretion of CCL2 coupled with dysregulated arginine-NO metabolism after Slc4a4 deletion. Using a model of ischemic stroke, we found that loss of Slc4a4 exacerbates BBB disruption and reactive gliosis, which were both rescued by pharmacological or genetic inhibition of the NO-CCL2 pathway in vivo. Together, our study identifies the astrocytic Slc4a4-NO-CCL2 axis as a pivotal mechanism controlling BBB integrity and repair, while providing insights for a novel therapeutic approach against BBB-related CNS disorders.

Doppler ultrasound investigation of female infertility.

This study reviewed recent advances in the use of Doppler ultrasonography for the management and prediction of female infertility outcomes of assisted reproductive technology (ART). Color or power Doppler and three-dimensional power Doppler ultrasound can be used to measure vessels near the ovaries, uterus, and endometrium to assess blood flow. Increased blood flow and reduced resistance to the ovaries, uterus, and endometrium are associated with improved pregnancy outcomes, and their measurement has been suggested as a key factor in ART procedural outcomes. Perifollicular vascularity indices can help predict oocyte quality and maturity. Likewise, endometrial and uterine vascularity could be associated with endometrial receptivity and may assist with embryo transfer timing and pregnancy outcome predictions. With the advancement of Doppler ultrasound technology, this highly potent examination will be used more widely in routine clinical settings for the treatment of female infertility.

A Comparison of Ultrasound Imaging Texture Analyses During the Early Postpartum With the Mode of Delivery.

BACKGROUND: Breastfeeding is beneficial to infants. However, cesarean section is reported to be a risk factor for unsuccessful breastfeeding. RESEARCH AIMS: (1) To extract discriminating data from texture analysis of breast ultrasound images in the immediate postpartum period; and (2) to compare the analysis results according to delivery mode. METHODS: A cross-sectional, prospective non-experimental design with a questionnaire and observational components was used. Participants (N = 30) were women who delivered neonates at a center from September 2020 to December 2020. The participants underwent ultrasound examination of bilateral breasts 7-14 days after delivery. Ultrasound images were collected for texture analysis. A questionnaire about breastfeeding patterns was given to the participants on the day of the ultrasound examination. RESULTS: No significant differences were found in texture analysis between the breasts of participants who had undergone Cesarean section and vaginal deliveries. The mean volume of total human milk produced in 1 day was significantly greater in the vaginal delivery group than in the cesarean section group (M = 350.87 ml, SD = 183.83 vs. M = 186.20 ml, SD = 184.02; p = .017). The pain score due to breast engorgement measured subjectively by participants was significantly lower in the vaginal delivery group than in the cesarean section group (M = 2.8, SD = 0.86 vs. M = 3.4, SD = 0.63; p = .047). CONCLUSION: Texture analysis of breast ultrasound images did not demonstrate difference between the cesarean section and vaginal delivery groups in the immediate postpartum period; nevertheless, cesarean section was independently associated with less successful breastfeeding.

CXCR4 expression is associated with proneural-to-mesenchymal transition in glioblastoma.

Glioblastoma (GBM) is the most common primary intracranial malignant tumor and consists of three molecular subtypes: proneural (PN), mesenchymal (MES) and classical (CL). Transition between PN to MES subtypes (PMT) is the glioma analog of the epithelial-mesenchymal transition (EMT) in carcinomas and is associated with resistance to therapy. CXCR4 signaling increases the expression of MES genes in glioma cell lines and promotes EMT in other cancers. RNA sequencing (RNAseq) data of PN GBMs in The Cancer Genome Atlas (TCGA) and secondary high-grade gliomas (HGGs) from an internal cohort were examined for correlation between CXCR4 expression and survival as well as expression of MES markers. Publicly available single-cell RNA sequencing (scRNAseq) data was analyzed for cell type specific CXCR4 expression. These results were validated in a genetic mouse model of PN GBM. Higher CXCR4 expression was associated with significantly reduced survival and increased expression of MES markers in TCGA and internal cohorts. CXCR4 was expressed in immune and tumor cells based on scRNAseq analysis. Higher CXCR4 expression within tumor cells on scRNAseq was associated with increased MES phenotype, suggesting a cell-autonomous effect. In a genetically engineered mouse model, tumors induced with CXCR4 exhibited a mesenchymal phenotype and shortened survival. These results suggest that CXCR4 signaling promotes PMT and shortens survival in GBM and highlights its inhibition as a potential therapeutic strategy.

Development of myelinating glia: An overview.

Myelin is essential to nervous system function, playing roles in saltatory conduction and trophic support. Oligodendrocytes (OLs) and Schwann cells (SCs) form myelin in the central and peripheral nervous systems respectively and follow different developmental paths. OLs are neural stem-cell derived and follow an intrinsic developmental program resulting in a largely irreversible differentiation state. During embryonic development, OL precursor cells (OPCs) are produced in distinct waves originating from different locations in the central nervous system, with a subset developing into myelinating OLs. OPCs remain evenly distributed throughout life, providing a population of responsive, multifunctional cells with the capacity to remyelinate after injury. SCs derive from the neural crest, are highly dependent on extrinsic signals, and have plastic differentiation states. SC precursors (SCPs) are produced in early embryonic nerve structures and differentiate into multipotent immature SCs (iSCs), which initiate radial sorting and differentiate into myelinating and non-myelinating SCs. Differentiated SCs retain the capacity to radically change phenotypes in response to external signals, including becoming repair SCs, which drive peripheral regeneration. While several transcription factors and myelin components are common between OLs and SCs, their differentiation mechanisms are highly distinct, owing to their unique lineages and their respective environments. In addition, both OLs and SCs respond to neuronal activity and regulate nervous system output in reciprocal manners, possibly through different pathways. Here, we outline their basic developmental programs, mechanisms regulating their differentiation, and recent advances in the field.

A Combined Conduit-Bioactive Hydrogel Approach for Regeneration of Transected Sciatic Nerves.

Transected peripheral nerve injury (PNI) affects the quality of life of patients, which leads to socioeconomic burden. Despite the existence of autografts and commercially available nerve guidance conduits (NGCs), the complexity of peripheral nerve regeneration requires further research in bioengineered NGCs to improve surgical outcomes. In this work, we introduce multidomain peptide (MDP) hydrogels, as intraluminal fillers, into electrospun poly(ε-caprolactone) (PCL) conduits to bridge 10 mm rat sciatic nerve defects. The efficacy of treatment groups was evaluated by electromyography and gait analysis to determine their electrical and motor recovery. We then studied the samples' histomorphometry with immunofluorescence staining and automatic axon counting/measurement software. Comparison with negative control group shows that PCL conduits filled with an anionic MDP may improve functional recovery 16 weeks postoperation, displaying higher amplitude of compound muscle action potential, greater gastrocnemius muscle weight retention, and earlier occurrence of flexion contracture. In contrast, PCL conduits filled with a cationic MDP showed the least degree of myelination and poor functional recovery. This phenomenon may be attributed to MDPs' difference in degradation time. Electrospun PCL conduits filled with an anionic MDP may become an attractive tissue engineering strategy for treating transected PNI when supplemented with other bioactive modifications.

ROR activation by Nobiletin enhances antitumor efficacy via suppression of IκB/NF-κB signaling in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by poor response to standard therapies and therefore unfavorable clinical outcomes. Better understanding of TNBC and new therapeutic strategies are urgently needed. ROR nuclear receptors are multifunctional transcription factors with important roles in circadian pathways and other processes including immunity and tumorigenesis. Nobiletin (NOB) is a natural compound known to display anticancer effects, and our previous studies showed that NOB activates RORs to enhance circadian rhythms and promote physiological fitness in mice. Here, we identified several TNBC cell lines being sensitive to NOB, by itself or in combination. Cell and xenograft experiments showed that NOB significantly inhibited TNBC cell proliferation and motility in vitro and in vivo. ROR loss- and gain-of-function studies showed concordant effects of the NOB-ROR axis on MDA-MB-231 cell growth. Mechanistically, we found that NOB activates ROR binding to the ROR response elements (RRE) of the IκBα promoter, and NOB strongly inhibited p65 nuclear translocation. Consistent with transcriptomic analysis indicating cancer and NF-κB signaling as major pathways altered by NOB, p65-inducible expression abolished NOB effects, illustrating a requisite role of NF-κB suppression mediating the anti-TNBC effect of NOB. Finally, in vivo mouse xenograft studies showed that NOB enhanced the antitumor efficacy in mammary fat pad implanted TNBC, as a single agent or in combination with the chemotherapy agent Docetaxel. Together, our study highlights an anti-TNBC mechanism of ROR-NOB via suppression of NF-κB signaling, suggesting novel preventive and chemotherapeutic strategies against this devastating disease.

The clock modulator Nobiletin mitigates astrogliosis-associated neuroinflammation and disease hallmarks in an Alzheimer's disease model.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder, and there is a pressing need to identify disease-modifying factors and devise interventional strategies. The circadian clock, our intrinsic biological timer, orchestrates various cellular and physiological processes including gene expression, sleep, and neuroinflammation; conversely, circadian dysfunctions are closely associated with and/or contribute to AD hallmarks. We previously reported that the natural compound Nobiletin (NOB) is a clock-enhancing modulator that promotes physiological health and healthy aging. In the current study, we treated the double transgenic AD model mice, APP/PS1, with NOB-containing diets. NOB significantly alleviated ß-amyloid burden in both the hippocampus and the cortex, and exhibited a trend to improve cognitive function in these mice. While several systemic parameters for circadian wheel-running activity, sleep, and metabolism were unchanged, NOB treatment showed a marked effect on the expression of clock and clock-controlled AD gene expression in the cortex. In accordance, cortical proteomic profiling demonstrated circadian time-dependent restoration of the protein landscape in APP/PS1 mice treated with NOB. More importantly, we found a potent efficacy of NOB to inhibit proinflammatory cytokine gene expression and inflammasome formation in the cortex, and immunostaining further revealed a specific effect to diminish astrogliosis, but not microgliosis, by NOB in APP/PS1 mice. Together, these results underscore beneficial effects of a clock modulator to mitigate pathological and cognitive hallmarks of AD, and suggest a possible mechanism via suppressing astrogliosis-associated neuroinflammation.

Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin.

Myelin is essential to neuronal health and CNS function, and oligodendrocytes (OLs) undergo a complex process of cytoskeletal remodeling to form compact myelin sheaths. We previously discovered that a formin protein, Dishevelled associated activator of morphogenesis 2 (Daam2), suppresses OL differentiation through Wnt signaling; however, its role in cytoskeletal control remains unknown. To investigate this, we used OL-specific Daam2 conditional knockout (Daam2 cKO) mice of either sex and found myelin decompaction during an active period of myelination in postnatal development and motor coordination deficits in adulthood. Using primary OL cultures, we found Daam2-depleted OLs showed morphologic dysregulation during differentiation, suggesting that Daam2 regulates the OL cytoskeleton. In vivo screening identified the actin regulators Rac1 and Gelsolin as possible effectors in Daam2-deficient OL cytoskeletal regulation. Using gain-of-function and loss-of-function (LOF) experiments in primary OLs, we found that Rac1 and Gelsolin operate downstream of Daam2 in OL differentiation, with Gelsolin and Daam2 promoting and inhibiting membrane spreading during late differentiation, respectively. In vivo experiments using Daam2 cKO mice revealed increased protein levels of Gelsolin in the developing white matter with no change in RNA levels, suggesting that Daam2 acts in a posttranslational manner to suppress Gelsolin levels. In vitro biochemical studies show Daam2 induces Gelsolin ubiquitination and degradation in OLs. Together, our studies show Daam2 is essential for formation of functional myelin through modulation of Gelsolin levels to regulate the OL cytoskeleton. These findings further demonstrate the critical role of cytoskeletal dynamics in myelination and reveal novel avenues for treatment of a variety of white matter diseases.SIGNIFICANCE STATEMENT Proper myelin formation is essential to CNS function, and oligodendrocytes (OLs) require extensive changes in the actin cytoskeleton to form myelin sheaths. Here, we show that the formin protein Dishevelled associated activator of morphogenesis 2 (Daam2) is necessary for myelin compaction during development and motor learning in adulthood. Further, we demonstrate that Daam2 regulates OL differentiation and morphology through actin regulators Rac1 and Gelsolin. Lastly, we find that Daam2 may control myelin compaction by modulating the ubiquitination and degradation of Gelsolin through recruitment of the E3 ubiquitin ligase Nedd4. These findings reveal novel pathways for regulating myelin structure and function during white matter development.

Regional heterogeneity of astrocyte morphogenesis dictated by the formin protein, Daam2, modifies circuit function.

Astrocytes display extraordinary morphological complexity that is essential to support brain circuit development and function. Formin proteins are key regulators of the cytoskeleton; however, their role in astrocyte morphogenesis across diverse brain regions and neural circuits is unknown. Here, we show that loss of the formin protein Daam2 in astrocytes increases morphological complexity in the cortex and olfactory bulb, but elicits opposing effects on astrocytic calcium dynamics. These differential physiological effects result in increased excitatory synaptic activity in the cortex and increased inhibitory synaptic activity in the olfactory bulb, leading to altered olfactory behaviors. Proteomic profiling and immunoprecipitation experiments identify Slc4a4 as a binding partner of Daam2 in the cortex, and combined deletion of Daam2 and Slc4a4 restores the morphological alterations seen in Daam2 mutants. Our results reveal new mechanisms regulating astrocyte morphology and show that congruent changes in astrocyte morphology can differentially influence circuit function.

Depletion of ST6GALNACIII retards A549 non-small cell lung cancer cell proliferation by downregulating transferrin receptor protein 1 expression.

Alterations in sialylation of terminal residues of glycoproteins have been implicated in forming tumor-associated glycans. ST6GALNAC transfers sialyl moiety to N-acetylgalactosamine residue via α2,6 linkage. Although the oncogenic characteristics of ST6GALNACI or II have been demonstrated in various cancer cells, the impact of ST6GALNACIII on tumor progression remains undefined. In this study, we evaluated the effect of ST6GALNACIII knockdown on the growth of A549 non-small cell lung cancer cells. ST6GALNACIII depletion resulted in significant retardation in growth of A549 cells under various culture conditions, including collagen-supported 3D culture and anchorage-independent soft agar culture conditions. Liquid chromatography with tandem mass spectrometry revealed that two glycopeptides of transferrin receptor protein 1 (TFR1) containing N-acetylhexosamine-sialic acid were not detected in ST6GALNACIII-depleted A549 cells compared with control cells. Subsequent lectin binding assay, western blotting, and real-time RT-PCR indicated that TFR1 sialylation was not significantly changed, but TFR1 protein and mRNA expressions were decreased after ST6GALNACIII knockdown. However, cell growth retardation by ST6GALNACIII knockdown was partially rescued by TFR1 overexpression. Additionally, TFR1 mRNA degradation was accelerated following ST6GALNACIII knockdown with concomitant reduction in mRNA levels of iron regulatory protein 1 and 2, the upstream regulators of TFR1 mRNA stability. Therefore, our results indicated an important role of ST6GALNACIII in promoting A549 cell growth through quantitative regulation of TFR1 expression and provided therapeutic implications for ST6GALNACIII targeting in tumor growth suppression in vivo.

The Significance of Planned Fertility Preservation for Women With Endometrioma Before an Expected Ovarian Cystectomy.

Endometrioma is known to reduce the ovarian reserve and the extent of the decrease is more severe when ovarian surgery is performed. Therefore, to prevent this decline in fertility, patients with endometrioma are considered candidates for preoperative fertility preservation (FP). In this study, we evaluate the efficacy of FP in women with endometrioma before planned ovarian surgery. A total of 95 cycles in 62 patients with endometrioma, undergoing controlled ovarian stimulation (COS) for FP using a gonadotropin-releasing hormone (GnRH) antagonist protocol before an expected ovarian surgery, were enrolled retrospectively. COS outcomes were compared according to endometrioma laterality. Additionally, first COS cycle outcomes in patients with endometrioma were compared with those in infertile patients, or in patients with a benign ovarian cyst using propensity score matching. When multiple COS cycles were performed, the results of cumulative cycles were analyzed. Embryo quality was worse in the bilateral endometrioma group. Compared with the infertile patient group, the patients with endometrioma had significantly lower Anti-Müllerian Hormone (AMH) and fewer numbers of oocytes retrieved (median, 3.3 vs. 1.2, p<0.001; 7.0 vs. 4.0, p=0.009, respectively). Compared with mature oocytes in infertile patients or patients with a benign cyst, mature oocytes were fewer in patients with endometrioma, but this was not statistically significant (median, 4.0 vs. 3.0, p=0.085; 5.5 vs. 3.0, p=0.052, respectively). The median value of the cumulative number of cryopreserved oocytes or embryos was 14.5 up to the fourth cycle compared to 3 up to the first cycle, with cumulative effect. Women with endometrioma should be counseled for FP before planned ovarian cystectomy. The number of cryopreserved oocytes or embryos can be increased by repeated cycles.

Self-assembling multidomain peptide hydrogels accelerate peripheral nerve regeneration after crush injury.

Multidomain peptide (MDP) hydrogels are a class of self-assembling materials that have been shown to elicit beneficial responses for soft tissue regeneration. However, their capacity to promote nervous system regeneration remains unknown. The peripheral nervous system (PNS) substantially recovers after injury, partly due to the abundance of extracellular matrix (ECM) components in its basal lamina. However, severe peripheral nerve injuries that significantly damage the ECM continue to be a major clinical challenge as they occur at a high rate and can be extremely detrimental to patients' quality of life. In this study, a panel of eight MDPs were designed to contain various motifs mimicking extracellular matrix components and growth factors and successfully self-assembled into injectable, nanofibrous hydrogels. Using an in vitro screening system, various lysine based MDPs were found to enhance neurite outgrowth. To test their capacity to promote nerve regeneration in vivo, rat sciatic nerve crush injury was performed with MDP hydrogels injected directly into the injury sites. MDP hydrogels were found to enhance macrophage recruitment to the injury site and degrade efficiently over time. Rats that were injected with the MDP hydrogel K2 and laminin motif-containing MDPs K2-IIKDI and K2-IKVAV were found to have significantly accelerated functional recovery and remyelination compared to those injected with HBSS or other MDPs. These results demonstrate that MDPs enhance neurite outgrowth and promote a multicellular pro-regenerative response in peripheral nerve injury. This study provides important insights into the potential of MDPs as biomaterials for nerve regeneration and other clinical applications.