CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system.

JOURNAL/nrgr/04.03/01300535-202508000-00031/figure1/v/2024-09-30T120553Z/r/image-tiff The protein connector enhancer of kinase suppressor of Ras 2 (CNKSR2), present in both the postsynaptic density and cytoplasm of neurons, is a scaffolding protein with several protein-binding domains. Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders, particularly intellectual disability, although the precise mechanism involved has not yet been fully understood. Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane, thereby influencing synaptic signaling and the morphogenesis of dendritic spines. However, the function of CNKSR2 in the cytoplasm remains to be elucidated. In this study, we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2. Through a combination of bioinformatic analysis and cytological experiments, we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome. We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290. Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2. When we downregulated CNKSR2 expression in mouse neuroblastoma cells (Neuro 2A), we observed significant changes in the expression of numerous centrosomal genes. This manipulation also affected centrosome-related functions, including cell size and shape, cell proliferation, and motility. Furthermore, we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder. Our findings establish a connection between CNKSR2 and the centrosome, and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

Gender-specific microbial signatures in saliva: Unveiling the association between the oral microbiome and the pathogenesis of glioma.

The intricate interplay between the human oral microbiome and systemic health is increasingly being recognized, particularly in the context of central nervous system pathologies such as glioblastoma. In this study, we aimed to elucidate gender-specific differences in the salivary microbiome of glioma patients by utilizing 16S rRNA sequencing data from publicly available salivary microbiome datasets. We conducted comprehensive bioinformatics analysis, encompassing quality control, noise reduction, species classification, and microbial community composition analysis at various taxonomic levels. Machine learning algorithms were employed to identify microbial signatures associated with glioma. When compared to healthy controls, our analysis revealed distinct differences in the salivary microbiota of glioma patients. Notably, the genera Leptotrichia and Atopobium exhibited significant variations in abundance between genders. Leptotrichia was prevalent in healthy females but exhibited a reduced abundance in female glioma patients. In contrast, Atopobium was more abundant in male glioma patients. These findings suggest that hormonal influences might play a role in shaping the salivary microbiome and its association with glioma. We utilized a combination of LASSO-logistic regression and random forest models for feature selection, and identified key microbial features that differentiated glioma patients from healthy controls. We developed a diagnostic model with high predictive accuracy and area under the curve and principal component analysis metrics confirmed its robustness. The analysis of microbial markers, including Atopobium and Leptotrichia, highlighted the potential of the salivary microbiota as a non-invasive biomarker for the diagnosis and prognosis of glioma. Our findings highlight significant gender-specific disparities in the salivary microbiome of patients with glioma, offering new insights into the pathogenesis of glioma and paving the way for innovative diagnostic and therapeutic strategies. The use of saliva as a diagnostic fluid, given its ease of collection and non-invasive nature, holds immense promise for monitoring systemic health and the trajectory of disease. Future research should focus on investigating the underlying mechanisms by which the salivary microbiome influences the development of glioma and identifying potential microbiome-targeted therapies to enhance the management of glioma.

The intratumoral microbiota biomarkers for predicting survival and efficacy of immunotherapy in patients with ovarian serous cystadenocarcinoma.

BACKGROUND: Ovarian serous cystadenocarcinoma, accounting for about 90% of ovarian cancers, is frequently diagnosed at advanced stages, leading to suboptimal treatment outcomes. Given the malignant nature of the disease, effective biomarkers for accurate prediction and personalized treatment remain an urgent clinical need. METHODS: In this study, we analyzed the microbial contents of 453 ovarian serous cystadenocarcinoma and 68 adjacent non-cancerous samples. A univariate Cox regression model was used to identify microorganisms significantly associated with survival and a prognostic risk score model constructed using LASSO Cox regression analysis. Patients were subsequently categorized into high-risk and low-risk groups based on their risk scores. RESULTS: Survival analysis revealed that patients in the low-risk group had a higher overall survival rate. A nomogram was constructed for easy visualization of the prognostic model. Analysis of immune cell infiltration and immune checkpoint gene expression in both groups showed that both parameters were positively correlated with the risk level, indicating an increased immune response in higher risk groups. CONCLUSION: Our findings suggest that microbial profiles in ovarian serous cystadenocarcinoma may serve as viable clinical prognostic indicators. This study provides novel insights into the potential impact of intratumoral microbial communities on disease prognosis and opens avenues for future therapeutic interventions targeting these microorganisms.

Blue-Emissive Antioxidant Carbon Dots Enhance Drought Resistance of Pea (Pisum sativum L.).

Prolonged drought conditions are a critical challenge for agricultural advancement, threatening food security and environmental equilibrium. To overcome these issues, enhancing plant resilience to drought is essential for plant growth and sustainable agriculture. In this study, blue-emitting antioxidant carbon dots (B-CDs), synthesized from citric acid and ascorbic acid, emerged as a promising solution to enhance the drought resistance of peas (Pisum sativum L.). B-CDs can efficiently scavenge reactive oxygen species (ROS), which are harmful in excess to plants under stress conditions. Through detailed experimental analyses and density functional theory (DFT) studies, it is found that these B-CDs possess structures featuring eight-membered aromatic rings with abundant oxygen-containing functional groups, providing active sites for reactions with ROS. The practical benefits of the B-CDs are evident in tests with pea plants exposed to drought conditions. These plants show a remarkable reduction in ROS accumulation, an increase in photosynthetic efficiency due to improved electron transfer rates, and significant growth enhancement. Compared to untreated controls under drought stress, the application of B-CDs results in an impressive increase in the fresh and dry weights of both the shoots and roots of pea seedlings by 39.5 and 43.2% for fresh weights and 121.0 and 73.7% for dry weights, respectively. This suggests that B-CDs can significantly mitigate the negative effects of drought on plants. Thus, leveraging B-CDs opens a novel avenue for enhancing plant resilience to abiotic stressors through nanotechnology, thereby offering a sustainable pathway to counter the challenges of drought in agriculture.

[Clinical remission and transmural healing of ustekinumab in patients with Crohn's disease].

OBJECTIVE: To treat the Crohn's disease (CD) patients with ustekinumab (UST), to eva-luate their clinical and endoscopic remission, and to evaluate their transmural response (TR) and transmural healing (TH) condition using intestinal ultrasonography (IUS). METHODS: Retrospective analysis was made on patients diagnosed with CD in Peking University People's Hospital from January 2020 to August 2022, who were treated with UST for remission induction and maintenance therapy. All the patients were evaluated on both week 8 and week 16/20 after treatment, including clinical, biochemical indicators, colonoscopy and IUS examination. RESULTS: A total of 13 patients were enrolled in this study, including 11 males and 2 females. The minimum age was 23 years, the maximum age was 73 years and the mean age was 36.92 years. All the patients were in the active stage of disease before treatment, and the average Best Crohn's disease activity index (Best CDAI) score was 270.12±105.55. In week 8, the Best CDAI score of the patients decreased from 270.12±105.55 to 133.16±48.66 (t=4.977, P < 0.001). Eight patients achieved clinical remission while 5 patients remained in the active stage. Nine patients underwent colonoscopy evaluation. The average simple endoscopic score for Crohn's disease (SES-CD) score decreased from 10.71±7.14 before treatment to 6.00±7.81(t=2.483, P=0.048) in week 16/20. Four patients achieved endoscopic remission while 5 patients did not. In week 8, 5 patients achieved TR, 2 patients achieved TH, the other 6 patients did not get TR or TH. In week 16/20, 6 patients achieved TR, 3 patients achieved TH while the other 4 patients did not get TR or TH. There was no significant statistical difference in the TR effect of UST between small intestine and colon lesions (Fisher test, P > 0.999). The rate of UST transmural response in the patients who had had previous biological agent therapy was lower than those with no previous biological agent therapy, but there was no significant statistical difference (Fisher test, P=0.491). CONCLUSION: After treatment of UST, the clinical and endoscopic conditions of the CD patients had been improved, and some patients could achieve clinical remission and endoscopic remission. UST had good TR and TH effects on CD. TR might appear in week 8, and the TR effect increased in week 16/20. There was no significant statistical difference in the TR effect between small intestine and colon lesions. TR effect of UST was better in the patients who had no previous biological agent therapy than those who had had other biological agents, but the result had no significant statistical difference.

Exploring prognostic microbiota markers in patients with endometrial carcinoma: Intratumoral insights.

Endometrial cancer, a leading gynecological malignancy, is profoundly influenced by the uterine microbiota, a key factor in disease prognosis and treatment. Our study underscores the distinct microbial compositions in endometrial cancer compared to adjacent non-cancerous tissues, revealing a dominant presence of p_Actinobacteria in cancerous tissues as opposed to p_Firmicutes in surrounding areas. Through comprehensive analysis, we identified 485 unique microorganisms in cancer tissues, 26 of which correlate with patient prognosis. Employing univariate Cox regression and LASSO regression analyses, we devised a microbial risk scoring model, effectively stratifying patients into high and low-risk categories, thereby providing predictive insights into their overall survival. We further developed a nomogram that incorporates the microbial risk score along with age, grade, and clinical stage, significantly enhancing the accuracy of our clinical prediction model for endometrial cancer. Moreover, our study delves into the differential immune landscapes of high-risk and low-risk patients. The low-risk group displayed a higher prevalence of activated B cells and increased T cell co-stimulation, indicative of a robust immune response. Conversely, high-risk patients showed elevated tumor immune dysfunction and exclusion scores, suggesting less favorable outcomes in immunotherapy. Notably, the efficacy of IPS-CTLA4 and PD1/PD-L1/PD-L2 blockers was substantially higher in the low-risk group, pointing to a more responsive immunotherapeutic approach. In summary, our research elucidates the unique microbial patterns in endometrial cancer and adjacent tissues, and establishes both a microbial risk score model and a clinical prediction nomogram. These findings highlight the potential of uterine microbiota as a biomarker for customizing treatment strategies, enabling precise interventions for high-risk patients while preventing overtreatment in low-risk cases. This study emphasizes the microbiota's role in tailoring immunotherapy, offering a novel perspective in the treatment and prognosis of endometrial cancer. Significantly, our study's expansive sample analysis from the TCGA-UCEC cohort, employing linear discriminant analysis effect size methodology, not only validates but also enhances our understanding of the microbiota's role in endometrial cancer, paving the way for novel diagnostic and therapeutic approaches in its management.

Outcomes of the Next In Vitro Fertilization Cycle in Women with Polycystic Ovary Syndrome after a Failed In Vitro Maturation Attempt.

BACKGROUND: In vitro maturation (IVM) is indicated in women with polycystic ovary syndrome (PCOS) who have a very good ovarian response during in vitro fertilization (IVF) and are therefore at high risk of ovarian hyperstimulation syndrome (OHSS). According to the latest practice committee document, IVM could be a major advance in assisted reproductive technology (ART) procedures (reduced cost and simplified treatment); nevertheless, retrospective studies of IVM versus IVF still demonstrate lower chances of a live birth with IVM. Could IVM prove to be an optimal first-line treatment approach? And limited information is available concerning the success of the subsequent IVF cycle after the failure of an IVM cycle. Does IVM treatment adversely affect the subsequent IVF cycle, and is this worth considering before performing the IVF cycle for women with PCOS? METHODS: This prospective nested case-control study at the Peking University Reproductive Medicine center in China was performed between March 2018 and September 2020. Women aged 20-38 years with PCOS and infertility and who were scheduled for their first IVF attempt were eligible. A total of 351 women were randomly allocated to receive one cycle of unstimulated natural IVM (n = 175) or one cycle of standard IVF with a flexible GnRH antagonist protocol followed by hCG as an ovulation trigger (n = 176). This study involved 234 women (58 women with no blastocysts in the first IVM cycle and 158 women who underwent the first IVF cycle). Cumulative live birth rate at 12 months after oocyte retrieval and OHSS of a standard controlled ovarian stimulation (COS) IVF cycle were compared between 58 women in an IVF cycle following a failed IVM cycle and 158 women who underwent the first IVF cycle. RESULTS: No significant differences were found in the cumulative live birth rate (CLBR), ongoing pregnancy rate, or clinical pregnancy rate at 12 months after oocyte retrieval between the two groups (56.9% vs. 58.9%, p = 0.795; 58.6% vs. 60.8%, p = 0.776; and 84.5% vs. 76.0%, p = 0.178). The incidence of moderate-to-severe OHSS was not significantly different between the groups (6.9% vs. 5.7%, p = 0.742). Additionally, there were no significant differences in the total gonadotropin dose, stimulation duration, number of retrieved oocytes, number of retrieved mature oocytes, or fertilization rates. CONCLUSIONS: Even if the first IVM attempt failed in subfertile women with PCOS, comparable cumulative live birth rates were observed in the subsequent IVF cycle. IVM treatment does not adversely affect the subsequent IVF cycle.

Expanding tubular microvessels on stiff substrates with endothelial cells and pericytes from the same adult tissue.

Endothelial cells (ECs) usually form a monolayer on two-dimensional (2D) stiff substrates and a tubular structure with soft hydrogels. The coculture models using ECs and pericytes derived from different adult tissues or pluripotent stem cells cannot mimic tissue-specific microvessels due to vascular heterogeneity. Our study established a method for expanding tubular microvessels on 2D stiff substrates with ECs and pericytes from the same adult tissue. We isolated microvessels from adult rat subcutaneous soft connective tissue and cultured them in the custom-made tubular microvascular growth medium on 2D stiff substrates (TGM2D). TGM2D promoted adult microvessel growth for at least 4 weeks and maintained a tubular morphology, contrary to the EC monolayer in the commercial medium EGM2MV. Transcriptomic analysis showed that TGM2D upregulated angiogenesis and vascular morphogenesis while suppressing oxidation and lipid metabolic pathways. Our method can be applied to other organs for expanding organ-specific microvessels for tissue engineering.

Efficient Tumor Immunotherapy through a Single Injection of Injectable Antigen/Adjuvant-Loaded Macroporous Silk Fibroin Microspheres.

Synthetic or natural materials have been used as vaccines in cancer immunotherapy. However, using them as vaccines necessitates multiple injections or surgical implantations. To tackle such daunting challenges, we develop an injectable macroporous Bombyx mori (B. mori) silk fibroin (SF) microsphere loaded with antigens and immune adjuvants to suppress established tumors with only a single injection. SF microspheres can serve as a scaffold by injection and avoid surgical injury as seen in traditional scaffold vaccines. The macroporous structure of the vaccine facilitates the recruitment of immune cells and promotes the activation of dendritic cells (DCs), resulting in a favorable immune microenvironment that further induces strong humoral and cellular immunity. We have also modified the vaccine into a booster version by simply allowing the antigens to be adsorbed onto the SF microspheres. The booster vaccine highly efficiently suppresses tumor growth by improving the cytotoxic T lymphocyte (CTL) response. In general, these results demonstrate that the macroporous SF microspheres can serve as a facile platform for tumor vaccine therapy in the future. Since the SF microspheres are also potential scaffolds for tissue regeneration, their use as a vaccine platform will enable their applications in eradicating tumors while regenerating healthy tissue to heal the tumor-site cavity.

Expansion of mouse castration-resistant intermediate prostate stem cells in vitro.

BACKGROUND: Most castration-resistant prostate cancers (CRPCs) have a luminal phenotype with high androgen receptor (AR) and prostate-specific antigen (PSA) expression. Currently, it is difficult to culture castration-resistant luminal cells with AR and PSA expression. METHODS: We formulated a custom-made medium and isolated primary cells from the prostate of adult wild-type (WT) and TRAMP mice. The cells were characterized by immunofluorescence staining, transcriptomic analysis, and qRT-PCR verification. Their self-renewal and differentiation potential in vitro and in vivo were examined. We treated the cells with androgen deprivation and enzalutamide and performed immunofluorescence staining and western blotting to analyze their expression of AR and PSA. RESULTS: We isolated a novel type of castration-resistant intermediate prostate stem cells (CRIPSCs) from adult WT and TRAMP mice. The mouse CRIPSCs proliferated rapidly in two-dimensional (2D) culture dishes and can be cultured for more than six months. The mouse CRIPSCs expressed luminal markers (AR, PSA, and Dsg4), basal markers (CK5 and p63), Psca, and the intermediate cell marker (Ivl). Transcriptomic analysis showed that the mouse CRIPSCs had upregulated signaling pathways related to cancer development and drug resistance. In the long-term culture, TRAMP CRIPSCs had higher expression of the genes related to stem cells and cancers than WT mice. Both WT and TRAMP CRIPSCs formed organoids in Matrigel. WT CRIPSCs did not form prostate tissues when transplanted in vivo without urogenital sinus mesenchyme (UGM) cells. In contrast, TRAMP CRIPSCs formed prostate ducts in NOG mice without UGM  cells and differentiated into luminal, basal, and neuroendocrine cells. Androgens regulated AR translocation between the nucleus and cytoplasm in the mouse CRIPSCs. Treatment of androgen deprivation  (ADT) and enzalutamide reduced AR expression in WT and TRAMP CRIPSCs; however, this treatment promoted PSA expression in TRAMP, while not WT CRIPSCs, similar to the clinical observations of CRPC. CONCLUSIONS: Our study established a method for isolating and expanding mouse CRIPSCs in 2D culture dishes. Mouse CRIPSCs had markers of basal and luminal cells, including AR and PSA, and can differentiate into prostate organoids and tissues. TRAMP CRIPSCs had elevated PSA expression upon ADT and enzalutamide treatment. Our method can be translated into clinical settings for CRPC precision medicine.

The dark side of synaptic proteins in tumours.

Research in the past decade has uncovered the essential role of the nervous system in the tumour microenvironment. The recent advances in cancer neuroscience, especially the discovery of neuron-tumour synaptic/perisynaptic structures, have revealed the dark side of synaptic proteins in the progression of brain tumours. Here, we provide an overview of the synaptic proteins expressed by tumour cells and analyse their molecular functions and organisation by comparing them with neuronal synaptic proteins. We focus on the studies of neuroligin-3, the glutamate receptors AMPAR and NMDAR and the synaptic scaffold protein DLGAP1, for their newly discovered regulatory role in the proliferation and progression of tumours. Progress in cancer neuroscience has brought novel insights into the treatment of cancers. In the last part of this review, we discuss the therapeutical strategies targeting synaptic proteins and the current challenges and possible toolkits regarding their clinical application in cancer treatment. Our understanding of cancer neuroscience is still in its infancy; deeper investigation of how tumour cells co-opt synaptic signaling will help fulfil the therapeutical potential of the synaptic proteins as promising anti-tumour targets.

Template-Free Synthesis of Porous Fluorescent Carbon Nanomaterials with Gluten for Intracellular Imaging and Drug Delivery.

A series of carbon nanomaterials, including carbon dots, carbon nanorings (CNRs), and porous carbon nanoballs, were facilely prepared by a template-free hydrothermal treatment of gluten as the sole carbon source. Driven by the hydrophobicity interaction, a concentration-dependent self-assembly of gluten was observed in an aqueous solution, leading to the subsequent formation of different morphologies of carbon nanomaterials in a hydrothermal treatment. Among these carbon nanomaterials, the CNRs exhibit bright photoluminescence with a quantum yield of 47.0%. Furthermore, CNRs also have a large surface area and low toxicity, making them an excellent drug carrier for chemotherapeutics. A model drug molecule doxorubicin (DOX) was successfully loaded on the CNRs, and the CNRs-DOX complexes exhibit a pH-dependent DOX release behavior. Compared with free DOX, the CNRs-DOX complexes can induce a higher level of apoptosis and lower level of necrosis, showing promise as anticancer agents.

Association of Insulin Resistance and Elevated Androgen Levels with Polycystic Ovarian Syndrome (PCOS): A Review of Literature.

The polycystic ovary syndrome (PCOS) is the disease featured by elevated levels of androgens, ovulatory dysfunction, and morphological abnormalities. At reproductive stage of women, the rate of PCOS occurrence is measured as 6-10% and the prevalence rate may be double. There are different pathophysiological factors involved in PCOS, and they play a major role in various abnormalities in individual patient. It is clear that there is noteworthy elevation of androgen in PCOS, causing substantial misery and infertility problems. The overexposure of androgen is directly linked with insulin resistance and hyperinsulinaemia. It has been reported previously that PCOS is related to cardiac metabolic miseries and potently increases the risk of heart diseases. Endometrial cancer is also a serious concern which is reported with exceedingly high incidence in women with PCOS. However, the overexposure of androgen has direct and specific influence on the development of insulin resistance. Although many factors are involved, resistance to the insulin and enhanced level of androgen are considered the major causes of PCOS. In the present review, we have focused on the pathophysiology and major revolutions of insulin resistance and excessive levels of androgen in females with PCOS.

Cadmium induced aggregation of orange-red emissive carbon dots with enhanced fluorescence for intracellular imaging.

Cadmium is a notorious toxic heavy metal, that poses serious threat to human health. Sensitive and selective detection of cadmium in cells is of great significance in poison screening and disease diagnosis. Orange-red emissive carbon dots (OR-CDs), prepared from the calcination of selected carbon sources 5-amino-1, 10-phenanthroline (Aphen) and salicylic acid (SA), were found to act as a "turn on" type fluorescence probe for Cd2+ detection. The structure and optical properties of OR-CDs were comprehensively investigated by both experimental characterizations and density functional theory (DFT) calculations. The OR-CDs consist of a basic unit of nine aromatic rings, and the N/O binding sites on the OR-CDs can specifically bind with Cd2+, leading to aggregation induced enhanced emission (AIEE). A detection limit of 0.30 µM was achieved for Cd2+ with a linear range of 0.80-100 µM. OR-CDs can not only be used for intracellular Cd2+ imaging but also have the potential to alleviate cadmium poison in living organisms.

In vitro maturation without gonadotropins versus in vitro fertilization with hyperstimulation in women with polycystic ovary syndrome: a non-inferiority randomized controlled trial.

STUDY QUESTION: Does in vitro maturation (IVM) result in non-inferior cumulative live birth rates compared to those after standard in vitro fertilization (IVF) in infertile women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: One cycle of IVM, without any stimulation, was inferior to one cycle of standard IVF in women with PCOS in terms of 6-month cumulative live birth rates, when choosing single vitrified-warmed blastocyst transfer. WHAT IS KNOWN ALREADY: IVM is an emerging alternative treatment for women with PCOS who need assisted reproductive technology. Since a minimal or even zero dose of gonadotropins are required in the IVM procedure, the occurrence of ovarian hyperstimulation syndrome (OHSS) is eliminated. Only one clinical trial comparing the pregnancy outcome between IVM with FSH priming and IVF has been reported. However, it is still unknown whether IVM treatment without any stimulation can offer a similar live birth outcome in women with PCOS as compared to that in women receiving the standard IVF procedure with ovarian stimulation. STUDY DESIGN, SIZE, DURATION: This single-centre, open-label randomized controlled non-inferiority trial in an academic infertility centre in China was performed between March 2018 and July 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 20-38 years with PCOS and infertility scheduled for their first IVF attempt were eligible. In total, 351 women were randomly allocated to receive one cycle of unstimulated IVM (n = 175) or one cycle of standard IVF with a flexible GnRH antagonist protocol and hCG as ovulatory trigger (n = 176). A freeze-all and single blastocyst transfer strategy was used in both groups. The primary outcome was ongoing pregnancy (leading to live birth) within 6 months after randomization. A non-inferiority margin of 15% was considered. MAIN RESULTS AND THE ROLE OF CHANCE: The IVM procedure without additional gonadotropin resulted in a lower ongoing pregnancy (leading to live birth) within 6 months after randomization compared to standard IVF treatment (22.3% vs. 50.6%; rate difference -28.3%; 95% confidence interval [CI]: -37.9% to -18.7%). Moderate-severe OHSS did not occur in the IVM group, while in the IVF group, ten women (5.7%) had moderate OHSS and one woman (0.6%) had severe OHSS. There was no statistically significant difference in the occurrence of obstetric and perinatal complications. LIMITATIONS, REASONS FOR CAUTION: The trial was conducted using an IVM protocol without additional stimulation in a single centre, which may limit its generalizability. In addition, a GnRH agonist trigger rather than hCG for IVF stimulation in women with PCOS would be more consistent with current clinical practice. WIDER IMPLICATIONS OF THE FINDINGS: Although IVM is considered to be a convenient, inexpensive and safe alternative to IVF for women with PCOS, our results indicated that one cycle of IVM without any stimulation was inferior to one cycle of standard IVF in terms of the cumulative live birth rate. The inferiority of IVM without ovarian stimulation could be mainly due to the limitations in the developmental potential of embryos. Further IVM development should be tested and validated in a freeze-only and blastocyst transfer setting. Further RCTs are needed to evaluate the effectiveness and safety of other IVM protocols or multiple cycles of IVM compared to IVF. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2016YFC1000201 and 2018YFC1002104) and the National Science Foundation of China (81730038). B.W.M. is supported by a NHMRC Investigator grant (GNT1176437). All other authors declare no competing interests. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT03463772. TRIAL REGISTRATION DATE: 29 January 2018. DATE OF FIRST PATIENT'S ENROLMENT: 16 March 2018.

Patterned vascularization in a directional ice-templated scaffold of decellularized matrix.

Vascularization is fundamental for large-scale tissue engineering. Most of the current vascularization strategies including microfluidics and three-dimensional (3D) printing aim to precisely fabricate microchannels for individual microvessels. However, few studies have examined the remodeling capacity of the microvessels in the engineered constructs, which is important for transplantation in vivo. Here we present a method for patterning microvessels in a directional ice-templated scaffold of decellularized porcine kidney extracellular matrix. The aligned microchannels made by directional ice templating allowed for fast and efficient cell seeding. The pure decellularized matrix without any fixatives or cross-linkers maximized the potential of tissue remodeling. Dramatical microvascular remodeling happened in the scaffold in 2 weeks, from small primary microvessel segments to long patterned microvessels. The majority of the microvessels were aligned in parallel and interconnected with each other to form a network. This method is compatible with other engineering techniques, such as microfluidics and 3D printing, and multiple cell types can be co-cultured to make complex vascularized tissue and organ models.

Comparison of in vitro maturation and in vitro fertilization for polycystic ovary syndrome patients: a systematic review and meta-analysis.

BACKGROUND: There are two common treatments for polycystic ovary syndrome (PCOS): in vitro fertilization (IVF) and in vitro maturation (IVM). Our study aimed to assess the clinical effects and safety of IVM versus IVF for PCOS. METHODS: We searched randomized controlled trials and retrospective cohort studies comparing IVM versus IVF for PCOS. Data were extracted from eligible studies. We sought to evaluate fertilization rate, clinical pregnancy rate, live birth rate, and miscarriage. Results were expressed as risk ratio (RR) with 95% confidence intervals (CIs). RESULTS: Eight studies with a total of 1,579 patients were included in the present study. According to the heterogeneity analysis, there were no differences between the IVM group and IVF group in terms of fertilization rate, clinical pregnancy rate and miscarriage. Additionally, the IVF group had a higher live birth rate than the IVM group (overall P=0.0007). Sensitivity analysis and funnel plot showed that our study was robust and based on the funnel plot this article had low publication bias. DISCUSSION: The findings of the present study indicated that IVM had similar clinical effects compared with IVF in patients with PCOS. However, IVM might be a suitable option for PCOS in terms of cost and successful pregnancy rate.

Proteomic Study Reveals Major Pathways Regulating the Development of Black Soldier Fly.

Nowadays, biodegrading organic waste, as a solution to confront environmental challenges, has attracted wide attention. A dipteran insect, black soldier fly (BSF), exhibits outstanding capability to convert organic waste into proteins and lipid resources, and thus, much interest has been shown in it. However, information of fundamental biology of BSF is still limited besides its recycling efficiency. In this work, we present a complete proteomic database of BSF at all instars (before prepupa). We further formulated the pathways corresponding to BSF development and built a relationship with the current genetic database. To achieve this, we investigated the proteomics of BSF during different periods. We identified 5036 proteins, and among them, 3905 proteins were annotated in the protein function database. illustrated three pathways related to major physiological processes including the insulin signaling pathway for feeding and growth, fatty acid biosynthesis pathway for fatty acid using, and toll/immune deficiency pathway for immune behavior. The proteins in these three pathways were matched with a published genetic database, and this reference library could be used for future BSF genetic engineering. In conclusion, this work provided a comprehensive protein library of BSF and expands the basic knowledge of BSF for future research.