The main purpose of this study is to compare the embryo development and clinical outcomes of women in different age groups undergoing in vitro fertilization (IVF) processes using ...gonadotrophin-releasing hormone (GnRH) antagonist protocol, GnRH agonist long protocol, and early follicular phase protocol. We aim to provide reliable reference for future clinical treatments.ObjectiveThe main purpose of this study is to compare the embryo development and clinical outcomes of women in different age groups undergoing in vitro fertilization (IVF) processes using gonadotrophin-releasing hormone (GnRH) antagonist protocol, GnRH agonist long protocol, and early follicular phase protocol. We aim to provide reliable reference for future clinical treatments.We conducted a detailed analysis of patients who underwent treatment between January 2021 and February 2023. 1) In the overall patient population, we comprehensively compared the basic characteristics, the embryo development, and the clinical outcomes of patients treated
Freezing severely impacts potato production. Deciphering the pathways and metabolites that regulate the freezing tolerance of potato is useful in cultivation and breeding for hardiness. In the ...present study,
was identified to be more freezing tolerant than
. Furthermore, the two genotypes before/after exposure to 4 °C for 7 d with additional -1 °C for 12 h were analysed by RNA-seq and metabolomics, and the results were compared with the previous -1 °C for 12 h. The results showed that
activated numerous genes that differed from those of
. Among the genes, five pathways, such as the hormone signalling pathway, which includes salicylic acid, were enriched. Further metabolomics analysis showed that the content of salicylic acid was improved in
in response to -1 °C for 12 h. Moreover, exogenous application of 0.1 mM salicylic acid to potato was shown to improve constitutive freezing tolerance and increase the expression of
. Following transcriptome and metabolome analyses, it was documented that the content of SA that increased in freezing-tolerant
after exposure to cold condition, associated with the SA signalling pathway, enhanced potato freezing tolerance, probably through
.
Background Amphiregulin (AR) is a growth factor that resembles the epidermal growth factor (EGF) and serves various functions in different cells. However, no systematic studies or reports on the role ...of AR in human oocytes have currently been performed or reported. This study aimed to explore the role of AR in human immature oocytes during in vitro maturation (IVM) and in vitro fertilization (IVF) in achieving better embryonic development and to provide a basis for the development of a pre-insemination culture medium specific for cumulus oocyte complexes (COCs). Methods First, we examined the concentration of AR in the follicular fluid (FF) of patients who underwent routine IVF and explored the correlation between AR levels and oocyte maturation and subsequent embryonic development. Second, AR was added to the IVM medium to culture immature oocytes and investigate whether AR could improve the effects of IVM. Finally, we pioneered the use of a fertilization medium supplemented with AR for the pre-insemination culture of COCs to explore whether the involvement of AR can promote the maturation and fertilization of IVF oocytes, as well as subsequent embryonic development. Results A total of 609 FF samples were examined, and a positive correlation between AR levels and blastocyst formation was observed. In our IVM study, the development potential and IVM rate of immature oocytes, as well as the fertilization rate of IVM oocytes in the AR-added groups, were ameliorated significantly compared to the control group (All P < 0.05). Only the IVM-50 group had a significantly higher blastocyst formation rate than the control group (P < 0.05). In the final IVF study, the maturation, fertilization, high-quality embryo, blastocyst formation, and high-quality blastocyst rates of the AR-added group were significantly higher than those of the control group (All P < 0.05). Conclusion AR levels in the FF positively correlated with blastocyst formation, and AR involvement in pre-insemination cultures of COCs can effectively improve laboratory outcomes in IVF. Furthermore, AR can directly promote the in vitro maturation and developmental potential of human immature oocytes at an optimal concentration of 50 ng/ml.
To evaluate whether melatonin (MT) supplementation during in vitro maturation (IVM) of human oocytes can reverse the age-related decline in oocyte quality.
We enrolled 172 patients aged ≥35 years ...(older reproductive-aged women) and 83 patients aged <35 years (young women) who underwent in vitro fertilization between 2019 and 2022. We conducted IVM with and without 10 μM MT in immature oocytes of different ages. Oocyte fertilization and embryo development were observed using a stereomicroscope. We assessed the immunofluorescence intensity of mitochondrial function, measured the copy number of mitochondrial DNA (mtDNA), and examined the spindle and chromosome composition in in vitro mature stage II (IVM-MII) oocytes using immunofluorescence and second-generation sequencing.
MT supplementation significantly improved the redox level in the IVM medium and IVM-MII oocytes in older reproductive-aged women. It also significantly increased the proportion of circular mtDNA and the adenosine triphosphate content in IVM-MII oocytes. In addition, the IVM-MII oocytes obtained with MT supplementation showed a significant improvement in the normal composition of the spindle and chromosomes. Thus, the aged immature oocytes also showed significantly improved maturation and blastocyst formation rates owing to the role of MT.
Supplementation with 10 μM MT in the IVM medium reverses the age-related decline in oocyte quality. Our findings provide a viable solution for enhancing fertility in older reproductive-aged women.
(1) Background: Single blastocyst transfers (SBT) and double blastocyst transfers (DBT) are widely used in clinical practice. The objective of this study was to investigate the application of these ...two strategies in women of different ages. (2) Methods: Analysis was carried out on 5477 frozen embryo transfer cycles of women in different ages. All the cycles were divided into three groups according to the age of the included women: <35, 35-39, and >39. The live birth rate (LBR) and multiple birth rate (MBR) between the SBT and DBT among these groups, respectively, were compared. (3) Results: In the women < 35 group, the LBR was similar in SBT and DBT, but the MBR was higher in DBT than SBT. In women 35-39, with >10 oocytes retrieved, the MBR in DBT was significantly higher than SBT, but there was no significant difference in LBR between the two groups; with ≤10 oocytes retrieved, the LBR in DBT were significantly higher than SBT, but the MBT was not significantly different between the two groups. In women > 39, the LBR and MBR were lower in the SBT than DBT, but the differences were not statistically significant. (4) Conclusions: Selective SET is appropriate for most young women, whereas older women are advised to make individualized choices based on the number of oocytes retrieved and blastocyst quality.
Freezing stress is a major limiting factor in crop production. To increase frost‐hardiness of crops via breeding, deciphering the genes conferring freezing‐tolerance is vital. Potato cultivars ...(Solanum tuberosum) are generally freezing‐sensitive, but some potato wild species are freezing‐tolerant, including Solanum commersonii, Solanum malmeanum and Solanum acaule. However, the underlying molecular mechanisms conferring the freezing‐tolerance to the wild species remain to be deciphered. In this study, five representative genotypes of the above‐mentioned species with distinct freezing‐tolerance were investigated. Comparative transcriptomics analysis showed that SaCBL1‐like (calcineurin B‐like protein) was upregulated substantially in all of the freezing‐tolerant genotypes. Transgenic overexpression and known‐down lines of SaCBL1‐like were examined. SaCBL1‐like was shown to confer freezing‐tolerance without significantly impacting main agricultural traits. A functional mechanism analysis showed that SaCBL1‐like increases the expression of the C‐repeat binding factor‐regulon as well as causes a prolonged higher expression of CBF1 after exposure to cold conditions. Furthermore, SaCBL1–like was found to only interact with SaCIPK3–1 (CBL‐interacting protein kinase) among all apparent cold‐responsive SaCIPKs. Our study identifies SaCBL1‐like to play a vital role in conferring freezing tolerance in potato, which may provide a basis for a targeted potato breeding for frost‐hardiness.
Summary statement
To increase frost‐hardiness of potato via breeding, deciphering the genes conferring freezing‐tolerance is essential. Freezing‐tolerant and sensitive potato genotypes were characterized experimentally and SaCBL1‐like was identified to positively regulate constitutive and cold‐acclimated freezing tolerance in potato.
In this clinical study, we investigated the potential of melatonin (MT) supplementation in the freeze-thaw medium used for cryopreserved human oocytes. In total, 152 patients who underwent in vitro ...fertilization between January 2020 and December 2022 were included and categorized into different groups as follows: the donor group, comprising 108 patients who donated their oocytes, with 34 patients using a vitrification and warming medium supplemented with MT (D-MT subgroup) and 74 patients using conventional medium without MT (D-0 subgroup); and the autologous group, comprising 38 patients who used their own oocytes, with 19 patients using medium supplemented with MT (A-MT subgroup) and 19 patients using medium without MT (A-0 subgroup). After thawing, the surviving oocytes in the D-MT and A-MT subgroups and D-0 and A-0 subgroups were cultured in a fertilization media with and without 10−9 MMT for 2.5 h, respectively, followed by intracytoplasmic sperm injection insemination, embryo culture, and transfer. The survival, cleavage, high-quality embryo, clinical pregnancy, ongoing pregnancy, and implantation rates were significantly higher in the D-MT subgroup than in the D-0 subgroup (all P < 0.05). Similarly, the survival, fertilization, high-quality embryo, and high-quality blastocyst rates were significantly higher in the A-MT subgroup than in the A-0 subgroup (all P < 0.05). These findings indicate that MT addition during cryopreservation can enhance the development of vitrified-warmed human oocytes and improve clinical outcomes.
•MT application in cryopreservation can enhance the development of freeze–thawed human oocytes and improve clinical outcomes.•This study suggest that heterogeneity issues do not need to be considered for oocyte donation therapy.•This study offers a promising solution regarding the cryopreservation of human oocytes.
Numerous advanced Large Language Models (LLMs) now support context lengths up to 128K, and some extend to 200K. Some benchmarks in the generic domain have also followed up on evaluating long-context ...capabilities. In the medical domain, tasks are distinctive due to the unique contexts and need for domain expertise, necessitating further evaluation. However, despite the frequent presence of long texts in medical scenarios, evaluation benchmarks of long-context capabilities for LLMs in this field are still rare. In this paper, we propose MedOdyssey, the first medical long-context benchmark with seven length levels ranging from 4K to 200K tokens. MedOdyssey consists of two primary components: the medical-context "needles in a haystack" task and a series of tasks specific to medical applications, together comprising 10 datasets. The first component includes challenges such as counter-intuitive reasoning and novel (unknown) facts injection to mitigate knowledge leakage and data contamination of LLMs. The second component confronts the challenge of requiring professional medical expertise. Especially, we design the ``Maximum Identical Context'' principle to improve fairness by guaranteeing that different LLMs observe as many identical contexts as possible. Our experiment evaluates advanced proprietary and open-source LLMs tailored for processing long contexts and presents detailed performance analyses. This highlights that LLMs still face challenges and need for further research in this area. Our code and data are released in the repository: \url{https://github.com/JOHNNY-fans/MedOdyssey.}
Large-scale language models (LLMs) have achieved remarkable success across various language tasks but suffer from hallucinations and temporal misalignment. To mitigate these shortcomings, ...Retrieval-augmented generation (RAG) has been utilized to provide external knowledge to facilitate the answer generation. However, applying such models to the medical domain faces several challenges due to the lack of domain-specific knowledge and the intricacy of real-world scenarios. In this study, we explore LLMs with RAG framework for knowledge-intensive tasks in the medical field. To evaluate the capabilities of LLMs, we introduce MedicineQA, a multi-round dialogue benchmark that simulates the real-world medication consultation scenario and requires LLMs to answer with retrieved evidence from the medicine database. MedicineQA contains 300 multi-round question-answering pairs, each embedded within a detailed dialogue history, highlighting the challenge posed by this knowledge-intensive task to current LLMs. We further propose a new \textit{Distill-Retrieve-Read} framework instead of the previous \textit{Retrieve-then-Read}. Specifically, the distillation and retrieval process utilizes a tool calling mechanism to formulate search queries that emulate the keyword-based inquiries used by search engines. With experimental results, we show that our framework brings notable performance improvements and surpasses the previous counterparts in the evidence retrieval process in terms of evidence retrieval accuracy. This advancement sheds light on applying RAG to the medical domain.
