Application of amphiregulin in IVM culture of immature human oocytes and pre-insemination culture for COCs in IVF cycles.

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.

Recycling Organic Dyes within the Metal-Organic Framework for Photothermal Conversion.

The pursuit of a straightforward method to recycle organic dyes from effluents and repurpose them into valuable materials represents a highly sought-after yet huge challenge within the realms of chemistry, environment, and materials science. In this context, we employ a host-guest strategy that leverages the recycling of the rhodamine B molecule within the porous structure of a metal-organic framework to facilitate photothermal conversion. This achievement is realized through the electrostatic interaction, which then gives rise to remarkable selectivity and unparalleled uptake capacity for the cationic rhodamine B molecule. Capitalizing on this approach, the application of a columnar device and membrane technology for efficiently trapping rhodamine B molecules becomes feasible. On account of the aggregation effect resulting from the confined pore structure of the host matrix, the fluorescence emission of the encapsulated RhB molecules is significantly reduced, which consequently enhances the photothermal performance of the hybrid material through nonradiative transition. Moreover, the photothermal conversion achieved showcases a myriad of high-performance applications, including bacterial inhibition against Escherichia coli and seawater desalination.

E-peroxone with a novel GDE decorated with hydrophobic membrane for the degradation of pyridine: Stability, byproducts and toxicity.

E-peroxone process is an emerging electrochemical oxidation process, based on ozone and the in-situ cathodic generation of H2O2, but the stability of cathode is one of the key restraining factors. In this study, we designed a multilayer gas diffusion electrode (GDE) decorated with a commercial hydrophobic membrane for the degradation of pyridine. It was found that a proper control of membrane pore sizes and hot-pressing temperature can significantly promote the GDE stability. Subsequently, key operational parameters of the constructed E-peroxone system were investigated, including the ozone concentration, current density, pH value, electrolyte type and initial concentration of pyridine. The degradation pathways were proposed according to six identified transformation products. The toxicity variation along the degradation progress was evaluated with microbial respiration tests and Toxicity Estimation Software Tool (T.E.S.T.) calculation and an efficient detoxification capacity of E-peroxone was observed. This research provides a theoretical basis and technical support for the development of highly efficient and stable E-peroxone system for the elimination of toxic organic contaminants.

Short-term high-light intensity and low temperature improve the quality and flavor of lettuce grown in plant factory.

BACKGROUND: Lettuce holds a prominent position in the year-round supply of vegetables, offering a rich array of health-beneficial substances, such as dietary fiber, phenolic compounds, lactucopicrin and lactucin. As such, its flavor has garnered increasing attention. Balancing the enhancement of beneficial compounds with the reduction of undesirable taste is a key focus of scientific research. To investigate short-term management to improve the nutritional quality and flavor of lettuce, combinations of different light intensities (200, 500 and 800 µm ol m-2 s-1) and temperatures (10 and 22 °C) were applied separately to 'Lollo Rosso' and 'Little Butter Lettuce' for 7 days before harvest. RESULTS: The results obtained showed that increasing light intensity at low temperatures decreased nitrate content and increased soluble sugar, soluble protein, anthocyanin and phenolic compound content. In the case of lettuce flavor, the bitterness-related metabolites such as lactucin and lactucopicrin were reduced with high light intensity at a low temperature of 10 °C. With this combination, the fructose and glucose contents increased, significantly improving lettuce flavor. CONCLUSION: Higher light intensity combined with low temperature for 7 days before harvest effectively improved the nutritional quality and flavor of lettuce, suggesting its great potential for use in horticultural practices. © 2024 Society of Chemical Industry.

Co-immobilization of crosslinked enzyme aggregates on lysozyme functionalized magnetic nanoparticles for enhancing stability and activity.

Surface chemistry of carriers plays a key role in enzyme loading capacity, structure rigidity, and thus catalyze activity of immobilized enzymes. In this work, the two model enzymes of horseradish peroxidase (HRP) and glucose oxidase (GOx) are co-immobilized on the lysozyme functionalized magnetic core-shell nanocomposites (LYZ@MCSNCs) to enhance their stability and activity. Briefly, the HRP and GOx aggregates are firstly formed under the crosslinker of trimesic acid, in which the loading amount and the rigidity of the enzyme can be further increased. Additionally, LYZ easily forms a robust anti-biofouling nanofilm on the surface of SiO2@Fe3O4 magnetic nanoparticles with abundant functional groups, which facilitate chemical crosslinking of HRP and GOx aggregates with minimized inactivation. The immobilized enzyme of HRP-GOx@LYZ@MCSNCs exhibited excellent recovery activity (95.6 %) higher than that of the free enzyme (HRP&GOx). Specifically, 85 % of relative activity was retained after seven cycles, while 73.5 % of initial activity was also remained after storage for 33 days at 4 °C. The thermal stability and pH adaptability of HRP-GOx@LYZ@MCSNCs were better than those of free enzyme of HRP&GOx. This study provides a mild and ecofriendly strategy for multienzyme co-immobilization based on LYZ functionalized magnetic nanoparticles using HRP and GOx as model enzymes.

Functional disability and receipt of informal care among Chinese adults living alone with cognitive impairment.

BACKGROUND: Adults with cognitive impairment are prone to living alone in large numbers but receive relatively little attention. This study aimed to evaluate whether living alone with cognitive impairment was associated with a higher burden of functional disability but lack of informal care. METHODS: 982 observations of adults living alone with cognitive impairment and 50,695 observations of adults living with others and with normal cognition were identified from 4 waves (2011/2012, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study (CHARLS). A matched comparator was selected using propensity score matching (1:2). Functional disability included disability in Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), and mobility. The time of receiving informal care was measured in monthly hours. RESULTS: Adults living alone with cognitive impairment demonstrated significantly higher odds ratio of ADL disability (OR = 1.59, 95 % CI: 1.30, 1.95), IADL disability (OR = 1.19, 95 % CI: 1.00, 1.44), mobility disability (OR = 1.38, 95 % CI: 1.12, 1.70), but received fewer hours of informal care (ß = -127.7 h per month, standard error = 25.83, P < 0.001), compared to the adults living with others and with normal cognition. CONCLUSIONS: This study highlights the high burden of functional disability but low coverage of informal care among Chinese adults living alone with cognitive impairment and calls for more resources to be allocated to this vulnerable subpopulation to improve the functional health and to increase the provision of long-term care services.

No association between oral contraceptive exposure and subsequent MS: A population-based nested case-control study in primary care.

BACKGROUND: Conflicting data exist around oral contraceptive exposure and subsequent multiple sclerosis (MS). OBJECTIVE: To use routinely collected primary healthcare data to explore the potential association between oral contraceptive exposure and subsequent MS in females at population level. METHODS: We performed a nested case-control study using electronic primary care data, with complete electronic ascertainment from 1990. Logistic regression was used to evaluate associations between contraceptive exposure and MS, without and with adjusting for age, ethnicity and deprivation. RESULTS: A total of 4455 females were included: 891 cases and 3564 controls. No association was seen between oral contraceptive exposure and subsequent MS, or between any contraceptive, combined oral contraceptive pill (COCP) or progesterone-only pill (POP) use 0-2, 2-5 or >5 years prior to MS. Conclusions: In the largest population-based study to date, we find no evidence of an association between oral contraceptive exposure and subsequent MS diagnosis.

CADM2 participates in endometriosis development by influencing the epithelial-mesenchymal transition.

Endometriosis (EM) is a common gynecologic condition that often leads to infertility in women of reproductive age. Cell adhesion molecule 2 (CADM2) is involved in maintaining cell adhesion and polarity, as well as suppressing tumors. However, the role and mechanism of CADM2 in endometriosis is unclear. Therefore, this study evaluated the expression levels of CADM2 and epithelial-mesenchymal transition (EMT)-related marker proteins (E-cadherin, α-SMA, and N-cadherin). Compared to normal endometrial tissue, CADM2 was expressed at low levels in ectopic endometrial tissue from patients with EM. We performed clone formation assays, wound healing assays, and Transwell cell invasion assays to investigate the effects of CADM2 on the biological behavior of endometriosis epithelial cells (11Z) and ectopic endometrial stromal cells (EESCs). The growth, migration, and invasion abilities of these cells were significantly inhibited by overexpression of CADM2. The results were reversed after the knockdown of CADM2. Finally, western blotting (WB) was utilized to detect the effect of CADM2 on EMT in endometriosis cells. CADM2 inhibited EMT in endometriosis cells. In conclusion, our study suggests that CADM2 is a negative regulator of endometriosis development and may inhibit endometriosis development by suppressing EMT.

A wild melon reference genome provides novel insights into the domestication of a key gene responsible for melon fruit acidity.

KEY MESSAGE: A wild melon reference genome elucidates the genomic basis of fruit acidity domestication. Structural variants (SVs) have been reported to impose major effects on agronomic traits, representing a significant contributor to crop domestication. However, the landscape of SVs between wild and cultivated melons is elusive and how SVs have contributed to melon domestication remains largely unexplored. Here, we report a 379-Mb chromosome-scale genome of a wild progenitor melon accession "P84", with a contig N50 of 14.9 Mb. Genome comparison identifies 10,589 SVs between P84 and four cultivated melons with 6937 not characterized in previously analysis of 25 melon genome sequences. Furthermore, the population-scale genotyping of these SVs was determined in 1175 accessions, and 18 GWAS signals including fruit acidity, fruit length, fruit weight, fruit color and sex determination were detected. Based on these genotyped SVs, we identified 3317 highly diverged SVs between wild and cultivated melons, which could be the potential SVs associated with domestication-related traits. Furthermore, we identify novel SVs affecting fruit acidity and proposed the diverged evolutionary trajectories of CmPH, a key regulator of melon fruit acidity, during domestication and selection of different populations. These results will offer valuable resources for genomic studies and genetic improvement in melon.

A systematic pan-cancer analysis identifies LDHA as a novel predictor for immunological, prognostic, and immunotherapy resistance.

Lactate dehydrogenase A (LDHA), a critical enzyme involved in glycolysis, is broadly involved multiple biological functions in human cancers. It is reported that LDHA can impact tumor immune surveillance and induce the transformation of tumor-associated macrophages, highlighting its unnoticed function of LDHA in immune system. However, in human cancers, the role of LDHA in prognosis and immunotherapy hasn't been investigated. In this study, we analyzed the expression pattern and prognostic value of LDHA in pan-cancer and explored its association between tumor microenvironment (TME), immune infiltration subtype, stemness scores, tumor mutation burden (TMB), and immunotherapy resistance. We found that LDHA expression is tumor heterogeneous and that its high expression is associated with poor prognosis in multiple human cancers. In addition, LDHA expression was positively correlated with the presence of mononuclear/macrophage cells, and also promoted the infiltration of a range of immune cells. Genomic alteration of LDHA was common in different types of cancer, while with prognostic value in pan-cancers. Pan-cancer analysis revealed that the significant correlations existed between LDHA expression and tumor microenvironment (including stromal cells and immune cells) as well as stemness scores (DNAss and RNAss) across cancer types. Drug sensitivity analysis also revealed that LDHA was able to predict response to chemotherapy and immunotherapy. Furthermore, it was confirmed that knockdown of LDHA reduced proliferation and migration ability of lung cancer cells. Taken together, LDHA could serve as a prognostic biomarker and a potential immunotherapy marker.

Screening of Endophytic Antagonistic Bacteria in Wheat and Evaluation of Biocontrol Potential against Wheat Stripe Rust.

Wheat stripe rust is globally one of the most important diseases affecting wheat. There is an urgent need to develop environmentally safe and durable biological control options to supplement the control that is achieved with breeding and fungicides. In this study, endophytic bacteria were isolated from healthy wheat through the tissue separation method. Antagonistic endophytic bacteria were screened based on the control effect of urediniospore germination and wheat stripe rust (WSR). The taxonomic status of antagonistic strains was determined based on morphological, physiological, and biochemical characteristics and molecular biological identification (16S rDNA and gyrB gene sequence analysis). Finally, the potential growth-promoting effect of different concentrations of antagonists on wheat seedlings and the biological control effect of WSR were studied. A total of 136 strains of endophytic bacteria belonging to 38 genera were isolated. Pseudomonas was the most common bacterial genus, with 29 isolates (21%). The biological control effect of different isolates was assessed using an urediniospore germination assay. The isolate XD29-G1 of Paenibacillus polymyxa had the best performance, with 85% inhibition of spore germination during primary screening. In the deep screening, the control effect of XD29-G1 on wheat stripe rust was 60%. The antagonist XD29-G1 promoted the germination of wheat seeds and the growth of wheat seedlings at a solution dilution of 10-7 cfu/mL. The pot experiment results showed that different dilution concentrations of the strain had different levels of antibacterial activity against WSR, with the concentration of 10-1 cfu/mL having the best control effect and a control efficiency of 61.19%. XD29-G1 has better biological control potential against wheat stripe rust.

CRISPR/Cas-based CAR-T cells: production and application.

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the treatment approach for cancer, autoimmune disease, and heart disease. The integration of CAR into T cells is typically facilitated by retroviral or lentiviral vectors. However, the random insertion of CARs can lead to issues like clonal expansion, oncogenic transformation, variegated transgene expression, and transcriptional silencing. The advent of precise gene editing technology, like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), allows for controlled and precise genome modification, facilitating the translation of CAR-T research to the clinical applications. This review aims to provide a comprehensive analysis of the application of CRISPR gene editing techniques in the context of precise deletion and insertion methodologies, with a specific focus on their potential for enhancing the development and utilization of CAR-T cell therapy.

Liposomal STAT3-Degrading PROTAC Prodrugs Promote Anti-Hepatocellular Carcinoma Immunity via Chemically Reprogramming Cancer Stem Cells.

Cancer stem cells (CSCs) with hyperactivated signal transducer and activator of transcription 3 (STAT3) are a major driver of hepatocellular carcinoma (HCC). Herein, we report a nanointegrative proteolysis-targeting chimera (PROTAC)-based STAT3 degradation strategy that enables efficient chemical reprogramming of HCC-associated CSCs, which potently inhibits CSC growth while evoking anti-HCC immune responses. The PROTAC prodrug was synthesized by conjugating the STAT3 binding domain (inS3) with a thioketal-caged E3 ligase ligand (VL-TK) via an oligo(ethylene glycol) linker (OEG) with tuned length and flexibility and encapsulating it in cRGD-modified cationic liposomes for CSC-targeted delivery while facilitating their lysosomal escape. The PROTAC prodrugs were activated by the upregulated ROS levels in CSCs and efficiently degraded STAT3 for chemical reprogramming, which would not only impair their stemness features but also remodel the immunosuppressive TME into an immunosupportive state to boost anti-HCC immunity. This strategy provides an approach for improving HCC treatment in clinics.

A Long Photoperiod Promoted the Development, Reproduction, and Predation of Harmonia axyridis Pallas (Coleoptera: Coccinellidae) at an Average Greenhouse Temperature during the Winter.

To explore the feasibility of adjusting the photoperiod to regulate the life parameters and predation ability of Harmonia axyridis Pallas in greenhouses during the winter, life tables were constructed for H. axyridis under the three following photoperiods: 9L:15D (light/dark), 12L:12D, and 16L:8D at 15 °C, an average greenhouse temperature during the winter when aphids severely damage vegetables. The effects of photoperiods on predation by this ladybird were tested in both laboratory and greenhouse settings. The results showed that increased illumination promoted the development and reproduction of H. axyridis; under medium and long photoperiods, the pre-adult periods were 3.61 days and 4.34 days shorter than that under the short photoperiod, respectively, and the fecundity increased by 1.78 and 2.41 times. Population parameters r, λ, and R0 increased as illumination time increased, whereas T decreased. Increased illumination also increased the predation by third- and fourth-instar larvae and adults. The amounts of predation by fourth-instar larvae and adults increased by 22.16% and 75.09% under the medium photoperiod, and those under the long photoperiod increased by 71.96% and 89.64%, respectively. The numbers of Myzus persicae Sulzer predated by H. axyridis under the long photoperiod were higher than those under the short photoperiod in a greenhouse, and the predation parameters were influenced.

Delays in Multiple Sclerosis diagnosis (DIMES): protocol for a multicentre, observational study of multiple sclerosis diagnostic pathways in the United Kingdom and Republic of Ireland.

BACKGROUND: Multiple sclerosis (MS) is a leading cause of non-traumatic disability in young adults. Accumulating evidence indicates early diagnosis and early treatment improves long-term outcomes. However, the MS diagnostic pathway is increasingly complex, and delays may occur at several stages. Factors causing delays remain understudied. We aim to quantify the time taken for MS to be diagnosed, and characterise the diagnostic pathway and initial care provided, in the United Kingdom (UK) and Republic of Ireland (ROI). METHODS: Delays In MultiplE Sclerosis diagnosis (DIMES) in the UK and ROI is a multicentre, observational, retrospective study that will be conducted via the Neurology and Neurosurgery Interest Group (NANSIG) collaborative network. Any hospital in the UK and ROI providing an MS diagnostic service is eligible to participate. Data on consecutive individuals newly diagnosed with MS between 1st July 2022 and 31st December 2022 will be collected. The primary outcomes are 1) time from symptoms/signs prompting referral to neurology, to MS diagnosis; and 2) time from referral to neurology for suspected MS, to MS diagnosis. Secondary outcomes include: MS symptoms, referring specialties, investigations performed, neurology appointments, functional status, use of disease modifying treatments, and support at diagnosis including physical activity, and follow up. Demographic characteristics of people newly diagnosed with MS will be summarised, adherence to quality standards summarised as percentages, and time-to-event variables presented with survival curves. Multivariable models will be used to investigate the association of demographic and clinical factors with time to MS diagnosis, as defined in our primary outcomes. DISCUSSION: DIMES aims to be the largest multicentre study of the MS diagnostic pathway in the UK and ROI. The proposed data collection provides insights that cannot be provided from contemporary registries, and the findings will inform approaches to MS services nationally in the future.

Integrative analysis revealed a correlation of PIAS family genes expression with prognosis, immunomodulation and chemotherapy.

BACKGROUND: Protein inhibitor of activated STATs (PIAS) has pleiotropic biological effects, such as protein post-translational modification, transcriptional coregulation and gene editing. It is reported that PIAS family genes are also correlated with immune cells infiltration in cancers that highlights their unnoticed biological role in tumor progression. However, the relationship of their expression with prognosis, immune cell infiltration, tumor microenvironment, and immunotherapy in pan-cancer has been rarely reported. METHODS: The multi-omics data were used to investigate the expression level of PIAS family members in pan-cancer, and the prognostic value of their expression in different tumors was analyzed by univariate Cox regression and Kaplan-Meier. Correlation analysis was used to investigate the relationship of PIAS gene expression with tumor microenvironment, immune infiltrating subtypes, stemness score and drug sensitivity. In addition, we also used wound healing and transwell assays to verify the biological effects of PIAS family gene expression on invasion and metastasis of HCC cells. RESULTS: We found that PIAS family genes expression is significantly heterogeneous in tumors by multi-genomic analysis, and associated with poor prognosis in patients with multiple types of cancer. Furthermore, we also found that genetic alterations of PIAS family genes were not only common in different types of human tumors, but were also significantly associated with disease-free survival (DFS) across pan-cancer. Single-cell analysis revealed that PIAS family genes were mainly distributed in monocytes/macrophages. Additionally, we also found that their expression was associated with tumor microenvironment (including stromal cells and immune cells) and stemness score (DNAss and RNAss). Drug sensitivity analysis showed that PIAS family genes were able to predict the response to chemotherapy and immunotherapy. PIAS family genes expression is closely related to tumor metastasis, especially PIAS3. High PIAS3 expression significantly promotes the migration and invasion of liver cancer cell lines (HCC-LM3 and MHCC97-H). CONCLUSIONS: Taking together, these findings contribute to determine whether the PIAS family genes are a potential oncogenic target gene, which have important contribution for the development of cancer immunotherapy.

Mechanism of traditional Chinese medicine in elderly diabetes mellitus and a systematic review of its clinical application.

Objective: Affected by aging, the elderly diabetes patients have many pathological characteristics different from the young people, including more complications, vascular aging, cognitive impairment, osteoporosis, and sarcopenia. This article will explore their pathogenesis and the mechanism of Traditional Chinese medicine (TCM) intervention, and use the method of systematic review to evaluate the clinical application of TCM in elderly diabetes. Method: Searching for randomized controlled trials (RCTs) published from January 2000 to November 2023 in the following databases: Web of Science, Pubmed, Embase, Cochrane Library, Sinomed, China National Knowledge Internet, Wanfang and VIP. They were evaluated by three subgroups of Traditional Chinese Prescription, Traditional Chinese patent medicines and Traditional Chinese medicine extracts for their common prescriptions, drugs, adverse reactions and the quality of them. Results and Conclusion: TCM has the advantages of multi-target and synergistic treatment in the treatment of elderly diabetes. However, current clinical researches have shortcomings including the inclusion of age criteria and diagnosis of subjects are unclear, imprecise research design, non-standard intervention measures, and its safety needs further exploration. In the future, the diagnosis of elderly people with diabetes needs to be further clarified. Traditional Chinese patent medicines included in the pharmacopoeia can be used to conduct more rigorous RCTs, and then gradually standardize the traditional Chinese medicine prescriptions and traditional Chinese medicine extracts, providing higher level evidence for the treatment of elderly diabetes with traditional Chinese medicine.