Size effect of mesoporous silica nanoparticles on regulating the immune effect of oral influenza split vaccine.

Mucosal immunization is a powerful weapon against viral infection. In this paper, large pore mesoporous silica nanoparticles (LMSN) with different particle sizes were synthesized for loading influenza split vaccine (SV) to explore the effect of nanoparticle sizes on mucosal immunization and adjuvant efficacy. Interestingly, it was found that among the three particle sizes of nanoparticles, only LMSN-M with around 250 nm could significantly enhance the mucosal immune effect of SV, possessing adjuvant effect. The results indicated that particle size affected the adjuvant effect of LMSN. There was no apparent difference in vaccine loading capacity of LMSN with different particle sizes, but the release of SV depended on the pore length of LMSN. The adjuvant effect of LMSN-M was attributed to its higher cellular uptake performance, intestine absorption and transport efficiency, and the ability to stimulate the maturation of dendritic cells. Simultaneously, compared with LMSN-S and LMSN-L, the more retention of LMSN-M in mesenteric lymph nodes increased the chance of interaction between vaccine and immune system, resulting in the enhanced immunity. This is the first time to study the impact of particle size of LMSN adjuvant on improving mucosal immunity of oral influenza vaccine, and the present work provides a scientific reference for adjuvant design of oral vaccine.

Glucose-responsive insulin microneedle patches for long-acting delivery and release visualization.

Limited drug loading and incomplete drug release are two major obstacles that traditional polymeric microneedles (MNs) have to overcome. For smart controlled-release MNs, since drug release duration is uncertain, a clear indication of the finish of drug release is also important for patient guidance on the timing of the next dose. In this study, MN with a triple structure of a glucose-responsive shell, loaded insulin powders and a colored propelling inner core (inspired by the mechanism of osmotic pump) was innovatively constructed. The MN patch could release insulin according to blood glucose levels (BGLs) and had excellent drug loading, more complete drug release, and good drug stability, which significantly prolonged the normoglycemic time. An approximately 0.3 cm2 patch has a hypoglycemic effect on diabetic mice for up to 24 h. Moreover, the fading of the inner core could indicate the release process of the loaded drug and can help to facilitate uninterrupted closed loop therapy for patients. The designed triple MN structure is also suitable, and can be used in the design of other smart MN drug delivery systems to further improve their drug loading capacity and simultaneously achieve more complete, smart controlled and visualized drug release.

Erratum: Author correction to "Immune-awakening Saccharomyces-inspired nanocarrier for oral target delivery to lymph and tumors" [Acta Pharmaceutica Sinica B 12 (2022) 4501-4518].

[This corrects the article DOI: 10.1016/j.apsb.2022.04.018.].

G-protein-coupled estrogen receptor 1 promotes peritoneal metastasis of gastric cancer through nicotinamide adenine dinucleotide kinase 1-mediated redox modulation.

Adipose tissue is the second most important site of estrogen production, where androgens are converted into estrogen by aromatase. While gastric cancer patients often develop adipocyte-rich peritoneal metastasis, the underlying mechanism remains unclear. In this study, we identified the G-protein-coupled estrogen receptor (GPER1) as a promoter of gastric cancer peritoneal metastasis. Functional in vitro studies revealed that ß-Estradiol (E2) or the GPER1 agonist G1 inhibited anoikis in gastric cancer cells. Additionally, genetic overexpression or knockout of GPER1 significantly inhibited or enhanced gastric cancer cell anoikis in vitro and peritoneal metastasis in vivo, respectively. Mechanically, GPER1 knockout disrupted the NADPH pool and increased reactive oxygen species (ROS) generation. Conversely, overexpression of GPER1 had the opposite effects. GPER1 suppressed nicotinamide adenine dinucleotide kinase 1(NADK1) ubiquitination and promoted its phosphorylation, which were responsible for the elevated expression of NADK1 at protein levels and activity, respectively. Moreover, genetic inhibition of NADK1 disrupted NADPH and redox homeostasis, leading to high levels of ROS and significant anoikis, which inhibited lung and peritoneal metastasis in cell-based xenograft models. In summary, our study suggests that inhibiting GPER1-mediated NADK1 activity and its ubiquitination may be a promising therapeutic strategy for peritoneal metastasis of gastric cancer.

Optimized strategies of ROS-based nanodynamic therapies for tumor theranostics.

Reactive oxygen species (ROS) play a crucial role in regulating the metabolism of tumor growth, metastasis, death and other biological processes. ROS-based nanodynamic therapies (NDTs) are becoming attractive due to non-invasive, low side effects and tumor-specific advantages. NDTs have rapidly developed into numerous branches, such as photodynamic therapy, chemodynamic therapy, sonodynamic therapy and so on. However, the complexity of the tumor microenvironment and the limitations of existing sensitizers have greatly restricted the therapeutic effects of NDTs, which heavily rely on ROS levels. To address the limitations of NDTs, various strategies have been developed to increase ROS yield, which is an urgent aspect for the positive development of NDTs. In this review, the nanodynamic potentiation strategies in terms of unique properties and universalities of NDTs are comprehensively outlined. We mainly summarize the current dilemmas faced by each NDT and the respective solutions. Meanwhile, the NDTs universalities-based potentiation strategies and NDTs-based combined treatments are elaborated. Finally, we conclude with a discussion of the key issues and challenges faced in the development and clinical transformation of NDTs.

Effects of SARS-CoV-2 infection on embryological outcomes in assisted reproductive technology during the Omicron epidemic.

BACKGROUND: The influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on assisted reproductive technology (ART) has received increasing attention. It has been reported that the SARS-CoV-2 RiboNucleic Acid (RNA) cannot be detected in follicular fluid and granulosa cells. However, the detection rate of SARS-CoV-2 RNA in immature oocytes and blastocysts has still unknown. Moreover, the effect of SARS-CoV-2 infection on embryological outcomes in ART during the Omicron epidemic is limited. METHODS: A prospective study was performed to explore the detection rate of viral RNA in biological specimens from patients who tested positive for SARS-CoV-2 RNA and the effects of SARS-CoV-2 infection on embryological outcomes. A total of 211 patients underwent transvaginal oocyte retrieval at the Third Affiliated Hospital of Guangzhou Medical University between December 13, 2022 and December 30, 2022. Prior to transvaginal oocyte retrieval, 61 individuals tested positive for SARS-CoV-2 RNA within 24 h. Follicular fluid was preserved during oocyte retrieval. Granular cells were collected after degranulation (Intracytoplasmic sperm injection only). Immature oocytes were collected at the end of the ICSI. Unavailable blastocysts were collected on day 6 (D6). The TIANLONG SARS-CoV-2 RT-PCR-Kit was used to detect SARS-CoV-2 RNA in all samples. The COVID-19 and Non COVID-19 groups were contrasted in the following areas: fertilization rate, 2PN rate, Day 3 (D3) available embryos rate, D3 good-quality embryos rate, blastocyst formation rate, good-quality blastocyst formation rate. RESULTS: All samples were negative except for an immature oocytes sample that was positive for SARS-CoV-2 viral RNA with a detection rate of 6.67%. Whether in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), the rate of fertilization, 2PN, D3 available embryos, D3 good-quality embryos, blastocyst formation, good-quality blastocyst formation was not significantly negative different between the COVID-19 and the Non COVID-19 groups. Our findings were validated by an overview of the embryological outcome from the cycles before SARS- Cov-2 infection from the same patient. CONCLUSIONS: Except for immature oocytes, none of the follicular fluid, granulosa cells, or blastocysts samples contained viral RNA. In addition, SARS-CoV-2 infection had no detrimental effects on the embryological outcomes of ART.

Ex Vivo Calcium Imaging for Drosophila Model of Epilepsy.

Epilepsy is a neurological disorder characterized by recurrent seizures, partially correlated with genetic origin, affecting over 70 million individuals worldwide. Despite the clinical importance of epilepsy, the functional analysis of neural activity in the central nervous system is still to be developed. Recent advancements in imaging technology, in combination with stable expression of genetically encoded calcium indicators, such as GCaMP6, have revolutionized the study of epilepsy at both brain-wide and single-cell resolution levels. Drosophila melanogaster has emerged as a tool for investigating the molecular and cellular mechanisms underlying epilepsy due to its sophisticated molecular genetics and behavioral assays. In this study, we present a novel and efficient protocol for ex vivo calcium imaging in GCaMP6-expressing adult Drosophila to monitor epileptiform activities. The whole brain is prepared from cac, a well-known epilepsy gene, knockdown flies for calcium imaging with a confocal microscope to identify the neural activity as a follow-up to the bang-sensitive seizure-like behavior assay. The cac knockdown flies showed a higher rate of seizure-like behavior and abnormal calcium activities, including more large spikes and fewer small spikes than wild-type flies. The calcium activities were correlated to seizure-like behavior. This methodology serves as an efficient methodology in screening the pathogenic genes for epilepsy and exploring the potential mechanism of epilepsy at the cellular level.

The impact of intermediate product imports on industrial pollution emissions: Evidence from 30 industries in China.

Open and sustainable development is the theme that underpins a country's high-quality economic development. This study uses GMM regression, mediation effect test to conduct empirical tests based on the panel data of China's industrial sectors from 2003 to 2015 to analyze the internal mechanism of the impact of intermediate product imports on China's industrial pollution emissions. The results show that (1) Intermediate product imports can significantly promote the emission reduction of industrial wastes, including wastewater, waste gas and solid waste. (2) Considering the differences in the level of pollution intensity, this paper classified the sample and found the impact is heterogeneous that for the heavily, moderately, lightly polluted industries, intermediate product imports have different negative impacts on their pollution emissions. (3) Intermediate products imports reduce industrial pollution emissions through import competition effect, variety effect and technology spillover effect, and all of them play a partial mediating role.

UBR4 deficiency causes male sterility and testis abnormal in Drosophila.

Introduction: It has been established that UBR4 encodes E3 ubiquitin ligase, which determines the specificity of substrate binding during protein ubiquitination and has been associated with various functions of the nervous system but not the reproductive system. Herein, we explored the role of UBR4 on fertility with a Drosophila model. Methods: Different Ubr4 knockdown flies were established using the UAS/GAL4 activating sequence system. Fertility, hatchability, and testis morphology were studied, and bioinformatics analyses were conducted. Our results indicated that UBR4 deficiency could induce male sterility and influent egg hatchability in Drosophila. Results: We found that Ubr4 deficiency affected the testis during morphological analysis. Proteomics analysis indicated 188 upregulated proteins and 175 downregulated proteins in the testis of Ubr4 knockdown flies. Gene Ontology analysis revealed significant upregulation of CG11598 and Sfp65A, and downregulation of Pelota in Ubr4 knockdown flies. These proteins were involved in the biometabolic or reproductive process in Drosophila. These regulated proteins are important in testis generation and sperm storage promotion. Bioinformatics analysis verified that UBR4 was low expressed in cryptorchidism patients, which further supported the important role of UBR4 in male fertility. Discussion: Overall, our findings suggest that UBR4 deficiency could promote male infertility and may be involved in the protein modification of UBR4 by upregulating Sfp65A and CG11598, whereas downregulating Pelota protein expression.

Effect of blastocyst quality on human sex ratio at birth in a single blastocyst frozen thawed embryo transfer cycle.

RESEARCH QUESTION: To determine whether blastocyst quality affects the sex ratio at birth through a single blastocyst frozen - thawed embryo transfer (SBFET) cycle. DESIGN: In this retrospective analysis, we examined 3,041 singleton infants born following SBFET between 2017 and 2020 at a single institution. We compared the sex ratios of these infants with respect to the blastocyst quality, embryo growth rate, and morphology. RESULTS: The main outcomes of this study were that the sex ratio (M/F) at birth of SBFET was 1.24. Mothers >40 years old had a considerably lower sex ratio than mothers <40 years old (0.39 vs. 1.23-1.28, p < .05). Transplanting high-quality blastocysts significantly increased the proportion of boys born (1.29 vs. 0.88, p < .05). There were no significant differences in the sex ratio with respect to the inner cell mass (ICM) score and expansion degree. Additionally, a high trophoblastic cell (TE) score resulted in a significantly higher sex ratio than the TE score with C (1.62 vs. 1.15 vs. 0.85, p < .001). Multivariable logistic regression analysis was performed to determine which variables were significant factors affecting sex ratio, and the outcomes were consistent with previous findings. CONCLUSIONS: Our study indicated that high-quality, especially good TE score, had a higher chance of resulting in a male infant than a female infant.

Embryo development and live birth resulted from artificial oocyte activation after microdissection testicular sperm extraction with ICSI in patients with non-obstructive azoospermia.

Introduction: The application of microdissection testicular sperm extraction (micro-TESE) to retrieve the sperm of patients with non-obstructive azoospermia (NOA) has greatly increased. Patients with NOA often have poor quality sperm. Unfortunately, there are few studies on artificial oocyte activation (AOA) performed on patients who successfully retrieved motile and immotile sperm by micro-TESE after intracytoplasmic sperm injection (ICSI). Therefore, this study sought to obtain more comprehensive evidence-based data and embryo development outcomes to aid consultation of patients with NOA who opted to receive assisted reproductive techniques and to determine whether AOA needs to be performed in different motile sperm after ICSI. Methods: This retrospective study involved 235 patients with NOA who underwent micro-TESE to retrieve adequate sperm for ICSI between January 2018 and December 2020. A total of 331 ICSI cycles were performed in the 235 couples. Embryological, clinical, and neonatal outcomes were demonstrated comprehensively between motile sperm and immotile sperm using AOA and non-AOA treatment. Results: Motile sperm injection with AOA (group 1) showed significantly higher fertility rate (72.77% vs. 67.59%, p=0.005), 2 pronucleus (2PN) fertility rate (64.33% vs. 60.22%, p=0.036), and miscarriage rate (17.65% vs. 2.44%, p=0.018) compared with motile sperm injection with non-AOA (group 2). Group 1 had comparable available embryo rate (41.29% vs. 40.74%, p=0.817), good embryo rate (13.44% vs. 15.44%, p=0.265), and without an embryo for transfer rate (10.85% vs. 9.90%, p=0.815) compared with group 2. Immotile sperm injection with AOA (group 3) displayed significantly higher fertility rate (78.56% vs. 67.59%, p=0.000), 2PN fertility rate (67.36% vs. 60.22%, p=0.001), without an embryo for transfer rate (23.76% vs. 9.90%, p=0.008), and miscarriage rate (20.00% vs. 2.44%, p=0.014), but significantly lower available embryo rate (26.63% vs.40.74%, p=0.000) and good embryo rate (15.44% vs. 6.99%, p=0.000) compared with group 2. In groups 1, 2, and 3, the rates of implantation (34.87%, 31.85% and 28.00%, respectively; p=0.408), clinical pregnancy (43.87%, 41.00%, and 34.48%, respectively; p=0.360) and live birth (36.13%, 40.00%, and 27.59%, respectively; p=0.194) were similar. Discussion: For those patients with NOA from whom adequate sperm were retrieved for ICSI, AOA could improve fertilization rate, but not embryo quality and live birth outcomes. For patients with NOA and only immotile sperm, AOA can help achieve acceptable fertilization rate and live birth outcomes. AOA is recommended for patients with NOA only when immotile sperm are injected.

Degradable iron-rich mesoporous dopamine as a dual-glutathione depletion nanoplatform for photothermal-enhanced ferroptosis and chemodynamic therapy.

Glutathione (GSH) is a crucial factor in limiting the effects of chemodynamic therapy (CDT) and ferroptosis, an iron-based cell death pathway. Based on this, we constructed iron-rich mesoporous dopamine (MPDA@Fe) nanovehicles with a dual-GSH depletion function by combining MPDA and Fe. Poly (ethylene glycol) (PEG) was further modified to provide desirable stability (PM@Fe) and glucose oxidase (GOx) was grafted onto PM@Fe (GPM@Fe) to address the limitation of hydrogen peroxide (H2O2). After the nanoparticles reached the tumor site, the weakly acidic microenvironment promoted the release of Fe. Then FeII reacted with H2O2 to generate hydroxyl radical (OH) and FeIII. The generated FeIII was reduced to FeII by GSH, which circularly participated in the Fenton reaction and continuously produced tumor inhibitory free radicals. Meanwhile, GOx consumed glucose to provide H2O2 for the reaction. MPDA had also been reported to deplete GSH. Therefore, dual consumption of GSH led to the destruction of intracellular redox balance and inhibition of glutathione-dependent peroxidase 4 (GPX4) expression, resulting in an increase in lipid peroxides (LPO) and further induction of ferroptosis. Additionally, MPDA-mediated photothermal therapy (PTT) raised the temperature of tumor area and produced photothermal-enhanced cascade effects. Hence, the synergistic strategy that combined dual-GSH depletion-induced ferroptosis, enhanced CDT and photothermal cascade enhancement based on MPDA@Fe could provide more directions for designing nanomedicines for cancer treatment.

No advantage of single day 6 good-quality blastocyst transfer versus single day 5 poor-quality blastocyst transfer in frozen-thawed cycles stratified by age: a retrospective study.

BACKGROUND: Blastocyst developmental speed, morphological grading and patient age are associated with pregnancy outcomes of frozen-thawed cycles. This study aimed to compare the clinical and neonatal outcomes between poor-quality D5 blastocysts and good-quality D6 blastocysts stratified by patient age. METHODS: A total of 1,623 cycles were divided into two groups: group A (n = 723) received one D5 poor-quality blastocyst; group B (n = 900) received one D6 good-quality blastocyst. Pregnancy and neonatal outcomes were compared among the four groups stratified by 35 years of age. RESULTS: When patients were in the same age group, there was no significant difference in terms of age, body mass index, infertility duration, infertility type, fertilization method, proportion of endometrial preparation protocols, and endometrial thickness between D5 poor-quality and D6 high-quality blastocysts groups. Live birth rate of D5 poor-quality blastocysts was higher than that of D6 high-quality blastocysts for patients aged < 35 years (35.48% vs. 31.13%, p > 0.05), but there was no statistical difference. The same trend was showed for patients aged ≥ 35 years (29.09% vs. 21.28%, p > 0.05). Moreover, when patients were in the same age category, there was no significant difference in terms of gestational age, birth weight, birth height, and rates of preterm birth, low birth weight, and very low birth weight between groups A and B. CONCLUSIONS: The preferential selection of poor-quality D5 blastocysts for transfer compared to high-quality D6 blastocysts is recommended, especially for advanced age patients. Single good-quality D6 blastocyst transfer can be considered for the acceptable live birth rate.

Oral spatial-to-point cascade targeting "sugar-coated bullets" for precise and safe chemotherapy by intervention Warburg effect.

Glycolysis plays a vital role in the development and progression of tumors. Inhibiting glycolysis via smart and safe methods serves as a promising target for cancer therapy. Here, an oral "sugar-coated bullet" aiming at intervening Warburg effect is designed by coating colloidal mesoporous silica nanoparticles (CMS) encapsulating glycolysis inhibitor shikonin (SHK) with dextran, namely DCMS/SHK. The solubility and drug-loading capacity of SHK were enhanced by the special structure of CMS. Besides, the tempting bullets possess the spatial-to-point cascade targeting ability in delivering SHK from the colonic lumen to colon cancer cells and finally to PKM2. After DCMS/SHK reaches the colon, the dextran is hydrolyzed by dextranase especially existing in the colon site to glucose and the carriers become glucose-coated nanoparticles. The glucose-cloak nanoparticles would be largely endocytosed by tumor cells and complete the efficient delivery of SHK. The encapsulated SHK can prevent the glycolysis of cancer cells and thus inhibit tumor growth effectively. This work presents an ingenious cascade colon-targeting strategy to treat colon cancer by destroying cell energy metabolism.

YWHAZ variation causes intellectual disability and global developmental delay with brain malformation.

YWHAZ encodes an adapter protein 14-3-3ζ, which is involved in many signaling pathways that control cellular proliferation, migration and differentiation. It has not been definitely correlated to any phenotype in OMIM. To investigate the role of YWHAZ gene in intellectual disability and global developmental delay, we conducted whole-exon sequencing in all of the available members from a large three-generation family and we discovered that a novel variant of the YWHAZ gene was associated with intellectual disability and global developmental delay. This variant is a missense mutation of YWHAZ, p.Lys49Asn/c.147A > T, which was found in all affected members but not found in other unaffected members. We also conducted computational modeling and knockdown/knockin with Drosophila to confirm the role of the YWHAZ variant in intellectual disability. Computational modeling showed that the binding energy was increased in the mutated protein combining with the ligand indicating that the c147A > T variation was a loss-of-function variant. Cognitive defects and mushroom body morphological abnormalities were observed in YWHAZ c.147A > T knockin flies. The YWHAZ knockdown flies also manifested serious cognitive defects with hyperactivity behaviors, which is consistent with the clinical features. Our clinical and experimental results consistently suggested that YWHAZ was a novel intellectual disability pathogenic gene.

Immune-awakening Saccharomyces-inspired nanocarrier for oral target delivery to lymph and tumors.

Utilization of the intestinal lymphatic pathway will allow extraordinary gains in lymph and tumors cascade-targeted delivery of oral drugs and awakening the innate/adaptive immunity of the body and the lesion microenvironment, in addition to improving oral bioavailability relative to other means of delivery of oral drugs. Here, inspired by the specific invasion route of intestinal microorganisms, we pioneered an immune-awakening Saccharomyces-inspired mesoporous silicon nanoparticle (yMSN) for the ingenious cascade-targeted delivery of therapeutic cancer vaccines and antitumor drugs to lymph and tumors via the intestinal lymphatic pathway. Encouragingly, yMSN high-loaded tumor-specific antigens (OVA, 11.9%) and anti-tumor drugs (Len, 28.6%) with high stability, namely Len/OVA/yMSN, efficiently co-delivered OVA and Len to their desired target sites. Moreover, yMSN concomitantly awakened the innate antitumor immunity of dendritic cells and macrophages, strengthening vaccine-induced adaptive immune responses and reversing macrophage-associated immunosuppression in the tumor microenvironment. Surprisingly, Len/OVA/yMSN treatment resulted in excellent synergistic antitumor efficacy and long-term antitumor memory in OVA-Hepa1-6-bearing mice. This high-performance nanocarrier provides a novel approach for lesion-targeting delivery of oral drugs accompanied with awakening of the innate/adaptive immunity of the lesion environment, and also represents a novel path for the oral delivery of diverse therapeutic agents targeting other lymph-mediated diseases.

Clinical application of noninvasive chromosomal screening for elective single-blastocyst transfer in frozen-thawed cycles.

BACKGROUND: The objective of this study was to explore the clinical application of noninvasive chromosomal screening (NICS) for elective single-blastocyst transfer (eSBT) in frozen-thawed cycles. METHODS: This study retrospectively analysed the data of 212 frozen-thawed single-blastocyst transfers performed in our centre from January 2019 to July 2019. The frozen embryos were selected based on morphological grades and placed in preincubation for 6 h after warming. Then spent microdroplet culture media of frozen-thawed blastocysts were harvested and subjected to NICS. The clinical outcomes were evaluated and further stratified analysis were performed, especially different fertilization approaches. RESULTS: The clinical pregnancy, ongoing pregnancy, and live birth rates in the euploidy group were significantly higher than those in the aneuploidy group (56.2% versus 29.4%) but were nonsignificantly different from those in the chaotic abnormal/NA embryos group (56.2% versus 60.4%). Compared with day6 (D6) blastocysts, D5 blastocysts had a nonsignificantly different euploidy rate (40.4% versus 48.1%, P = 0.320) but significantly increased clinical pregnancy (57.7% versus 22.2%, P < 0.001), ongoing pregnancy (48.1% versus 14.8%, P < 0.001), and live birth rates (48.1% versus 13.0%, P < 0.001). The percentage of chaotic abnormal/NA embryos group was significantly higher among D5 embryos than among D6 embryos (30.1% versus 11.1%, P = 0.006). The percentage of aneuploid embryos was higher among the embryos with lower morphological quality(21.5% among 'good' embryos versus 34.6% among 'fair' embryos versus 46.0% among 'poor' embryos, P = 0.013); correspondingly, the overall clinical pregnancy, ongoing pregnancy and live birth rate rates showed similar declines. CONCLUSIONS: NICS combined with morphological assessment is an effective tool to guide frozen-thawed SBT. The optimal embryo for SBT is a 'euploid embryo with good morphology', followed sequentially by a 'chaotic abnormal/NA embryo with good morphology', 'euploid embryo with fair morphology', and 'chaotic abnormal/NA embryo with fair morphology'.

Mesenchymal stem cell therapy for ischemic stroke: Novel insight into the crosstalk with immune cells.

Stroke, a cerebrovascular accident, is prevalent and the second highest cause of death globally across patient populations; it is as a significant cause of morbidity and mortality. Mesenchymal stem cell (MSC) transplantation is emerging as a promising treatment for alleviating neurological deficits, as indicated by a great number of animal and clinical studies. The potential of regulating the immune system is currently being explored as a therapeutic target after ischemic stroke. This study will discuss recent evidence that MSCs can harness the immune system by interacting with immune cells to boost neurologic recovery effectively. Moreover, a notion will be given to MSCs participating in multiple pathological processes, such as increasing cell survival angiogenesis and suppressing cell apoptosis and autophagy in several phases of ischemic stroke, consequently promoting neurological function recovery. We will conclude the review by highlighting the clinical opportunities for MSCs by reviewing the safety, feasibility, and efficacy of MSCs therapy.

Effects of vitrified cryopreservation duration on IVF and neonatal outcomes.

BACKGROUND: In this study, we aimed to evaluate the impact of the duration of cryopreservation storage on embryo viability, implantation competence, pregnancy outcome and neonatal outcomes. METHODS: We retrospectively evaluated the outcomes of patients who underwent IVF with vitrified cryopreserved embryos between January 2004 and August 2019 by following the first frozen embryo transfer cycles within the study period. A total of 31,143 patients met the inclusion criteria and were grouped according to the embryo storage time as follows: Group 1 (n = 20,926),1-90 days; Group 2 (n = 6,472), 91-180 days; Group 3 (n = 2,237), 181-365 days; Group 4 (n = 746), 366-730 days; and Group 5 (n = 762), > 731 days. RESULTS: The embryo survival rate decreased significantly with longer durations of cryopreservation. The highest and lowest survival rate was recorded in Group 1 and Group 5, respectively (34853/35338; 98.63% vs. 1281/1801; 71.13%; P < 0.01). The human chorionic gonadotropin (HCG) detection and clinical pregnancy rate was highest in Group 1 (57.85% and 55. 26%, respectively; P < 0.01). Short-term cryopreservation (≤ 3 months) is associated with higher rates of clinical pregnancy. There were no significant differences in neonatal birth weight, neonatal height and congenital anomalies among the groups (P > 0. 05). CONCLUSION: The prolonged storage time of vitrified embryos negatively affected survival rate and clinical pregnancy rate. It did not have a significant influence on neonatal health. This study provides new findings about the relationship between prolonged storage time of vitrified embryos and clinical outcomes and offers evidence for the safety of using long-stored embryos after vitrification.