Developing patient-derived organoids to identify JX24120 inhibit SAMe synthesis in endometrial cancer by targeting MAT2B.

Endometrial cancer (EC) is one of the most common gynecologic malignancies, which lacking effective drugs for intractable conditions or patients unsuitable for surgeries. Recently, the patient-derived organoids (PDOs) are found feasible for cancer research and drug discoveries. Here, we established a series of PDOs from EC and performed drug repurposing screening and mechanism analysis for cancer treatment. We confirmed that the regulatory ß subunit of methionine adenosyltransferase (MAT2B) is highly correlated with malignant progression in endometrial cancer. Through drug screening on PDOs, we identify JX24120, chlorpromazine derivative, as a specific inhibitor for MAT2B, which directly binds to MAT2B (Kd = 4.724µM) and inhibits the viability of EC PDOs and canonical cell lines. Correspondingly, gene editing assessment demonstrates that JX24120 suppresses tumor growth depending on the presence of MAT2B in vivo and in vitro. Mechanistically, JX24120 induces inhibition of S-adenosylmethionine (SAMe) synthesis, leading to suppressed mTORC1 signaling, abnormal energy metabolism and protein synthesis, and eventually apoptosis. Taken together, our study offers a novel approach for drug discovery and efficacy assessment by using the PDOs model. These findings suggested that JX24120 may be a potent MAT2B inhibitor and will hopefully serve as a prospective compound for endometrial cancer therapy.

Response of soil microbial community structure and function to the sewage leakage: A case study of a 25-year-old cesspool.

Providing many millions of rural households with decentralized sanitation facilities remains challenging. In undeveloped areas, cesspools have still been widely used due to technologically simple and low-cost. However, the influence of cesspools on the surrounding soil remains unclear. In this study, we investigated the influence of a 25-year-old household cesspool on soil physicochemical factors, microbial community composition and function, pathogens and antibiotic resistance genes (ARGs). Soil at the depth around the sewage liquid level (D70) was mostly disturbed where TOC, NO3-N and TP was increased to 16.8 g/kg, 18.2 mg/kg and 1.02 mg/kg respectively. Correspondingly, the element cycling genes of carbon fixation, methanotrophy, nitrogen fixation, ammonia oxidation, and nitrate reduction etc., were increased at D70. Notably, human derived pathogens such as Enterobacter, Salmonella, Pseudomonas aeruginosa, Klebsiella pneumoniae, Prevotella, and Vibrio were highly enriched by 5-10 folders in D70, indicating the potential health risk to human. Mantel tests suggested that EC, TP, pH, NH3-N and particularly NO3-N are important factors that influence the microbial community and element cycling genes in cesspool-affected soil. Overall, this study revealed the impact of household cesspool leakage on the surrounding soil and provided information for the selection and construction of basic sanitation facilities in poor regions.

Vernalization promotes bolting in sugar beet by inhibiting the transcriptional repressors of BvGI.

Sugar beet (Beta vulgaris L.), a biennial sugar crop, contributes about 16% of the world's sugar production. The transition from vegetative growth, during which sugar accumulated in beet, to reproductive growth, during which sugar exhausted in beet, is determined by vernalization and photoperiod. GIGANTEA (GI) is a key photoperiodic flowering gene that is induced by vernalization in sugar beet. To identify the upstream regulatory factors of BvGI, candidate transcription factors (TF) that were co-expressed with BvGI and could bind to the BvGI promoter were screened based on weighted gene co-expression network analysis (WGCNA) and TF binding site prediction. Subsequently, their transcriptional regulatory role on the BvGI was validated through subcellular localization, dual-luciferase assays and yeast transformation tests. A total of 7,586 differentially expressed genes were identified after vernalization and divided into 18 co-expression modules by WGCNA, of which one (MEcyan) and two (MEdarkorange2 and MEmidnightblue) modules were positively and negatively correlated with the expression of BvGI, respectively. TF binding site predictions using PlantTFDB enabled the screening of BvLHY, BvTCP4 and BvCRF4 as candidate TFs that negatively regulated the expression of BvGI by affecting its transcription. Subcellular localization showed that BvLHY, BvTCP4 and BvCRF4 were localized to the nucleus. The results of dual-luciferase assays and yeast transformation tests showed that the relative luciferase activity and expression of HIS3 was reduced in the BvLHY, BvTCP4 and BvCRF4 transformants, which suggested that the three TFs inhibited the BvGI promoter. In addition, real-time quantitative reverse transcription PCR showed that BvLHY and BvTCP4 exhibited rhythmic expression characteristics similar to that of BvGI, while BvCRF4 did not. Our results revealed that vernalization crosstalked with the photoperiod pathway to initiate bolting in sugar beet by inhibiting the transcriptional repressors of BvGI.

Processing of angiocrine alarmin IL-1α in endothelial cells promotes lung and liver fibrosis.

BACKGROUND: Fibrosis results from excessive scar formation after tissue injury. Injured cells release alarmins such as interleukin 1 (IL-1) α and ß as primary mediators initiating tissue repair. However, how alarmins from different cell types differentially regulate fibrosis remains to be explored. METHODS: Here, we used tissue specific knockout strategy to illustrate a unique contribution of endothelial cell-derived IL-1α to lung and liver fibrosis. The two fibrotic animal model triggered by bleomycin and CCl4 were used to study the effects of endothelial paracrine/angiocrine IL-1α in fibrotic progression. Human umbilical vein endothelial cells (HUVEC) were performed to explore the production of angiocrine IL-1α at both transcriptional and post-transcriptional levels in vitro. RESULTS: We found that endothelial paracrine/angiocrine IL-1α primarily promotes lung and liver fibrosis during the early phase of organ repair. By contrast, myeloid cell-specific ablation of IL-1α in mice resulted in little influence on fibrosis, suggesting the specific pro-fibrotic role of IL-1α from endothelial cell but not macrophage. In vitro study revealed a coordinated regulation of IL-1α production in human primary endothelial cells at both transcriptional and post-transcriptional levels. Specifically, the transcription of IL-1α is regulated by RIPK1, and after caspase-8 (CASP8) cleaves the precursor form of IL-1α, its secretion is triggered by ion channel Pannexin 1 upon CASP8 cleavage. CONCLUSIONS: Endothelial cell-produced IL-1α plays a unique role in promoting organ fibrosis. Furthermore, the release of this angiocrine alarmin relies on a unique molecular mechanism involving RIPK1, CASP8, and ion channel Pannexin 1.

Self-Assembled Tetraphenylethene-Based Nanoaggregates with Tunable Electrochemiluminescence for the Ultrasensitive Detection of E. coli.

As an effective ECL emitter, tetraphenylethene (TPE)-based molecules have recently been reported with aggregation-induced electrochemiluminescence (AIECL) property, while it is still a big challenge to control its aggregation states and obtain uniform aggregates with intense ECL emission. In this study, we develop three TPE derivatives carrying a pyridinium group, an alkyl chain, and a quaternary ammonium group via the Menschutkin reaction. The resulting molecules exhibit significantly red-shifted FL and enhanced ECL emissions due to the tunable reduction of the energy gap between the highest occupied molecular orbitals (HOMOs) and the lowest unoccupied molecular orbitals (LUMOs). More importantly, the amphiphilicity of the as-developed molecules enables their spontaneous self-assembly into well-controlled spherical nanoaggregates, and the ECL intensity of nanoaggregates with 3 -CH2- (named as C3) is 17.0-fold higher compared to that of the original 4-(4-(1,2,2-triphenylvinyl)phenyl)pyridine (TPP) molecule. These cationic nanoaggregates demonstrate a high affinity toward bacteria, and an ECL sensor for the profiling of Escherichia coli (E. coli) was developed with a broad linear range and good selectivity in the presence of an E. coli-specific aptamer. This study provides an effective way to enhance the ECL emission of TPE molecules through their derivatization and a simple way to prepare well-controlled AIECL nanoaggregates for ECL application.

Targeting GRP75 with a Chlorpromazine Derivative Inhibits Endometrial Cancer Progression Through GRP75-IP3R-Ca2+-AMPK Axis.

Tumors often overexpress glucose-regulated proteins, and agents that interfere with the production or activity of these proteins may represent novel cancer treatments. The chlorpromazine derivative JX57 exhibits promising effects against endometrial cancer with minimal extrapyramidal side effects; however, its mechanisms of action are currently unknown. Here, glucose-regulated protein 75 kD (GRP75) is identified as a direct target of JX57 using activity-based protein profiling and loss-of-function experiments. The findings show that GRP75 is necessary for the biological activity of JX57, as JX57 exhibits moderate anticancer properties in GRP75-deficient cancer cells, both in vitro and in vivo. High GRP75 expression is correlated with poor differentiation and poor survival in patients with endometrial cancer, whereas the knockdown of GRP75 can significantly suppress tumor growth. Mechanistically, the direct binding of JX57 to GRP75 impairs the structure of the mitochondria-associated endoplasmic reticulum membrane and disrupts the endoplasmic reticulum-mitochondrial calcium homeostasis, resulting in a mitochondrial energy crisis and AMP-activated protein kinase activation. Taken together, these findings highlight GRP75 as a potential prognostic biomarker and direct therapeutic target in endometrial cancer and suggest that the chlorpromazine derivative JX57 can potentially be a new therapeutic option for endometrial cancer.

HPV prevalence and distribution characteristics in postmenopausal women from Nanjing, China.

BACKGROUND: Cervical cancer is strongly associated with human papillomavirus (HPV) infection. In this retrospective study, we analyzed the data of postmenopausal women who were tested for HPV in Nanjing First Hospital from 2019 to 2021. METHODS: We retrospectively analyzed the data of 14,608 postmenopausal women aged 45-90 years, who underwent HPV examination in Nanjing First Hospital between January 2019 and December 2021. All participants were tested for 23 HPV genotypes. We subsequently analyzed the infection rate and evaluated the distribution of HPV using the chi-square test. RESULTS: Our results showed that the HPV infection rate in postmenopausal women in Nanjing, China was 22.36%. In terms of age group, the infection rate was 19.54%, 24.30%, 26.58%, and 14.99% in those aged ≤ 50, 51-60, 61-70, and ≥ 71 years, respectively. The most common HPV subtypes were HPV52 (22.1 3%), HPV58 (15.86%), HPV53 (14.17%), HPV16 (12.61%), and HPV81 (11.66%), in that order. The single-HPV infection rate was 14.23%, and the multiple-genotype infection rate was 8.14% (1189/14,608). CONCLUSIONS: This study showed that in Nanjing, China, the different age groups of post-menopausal women could have different rates of HPV infection, and the most common types were HPV52, HPV58, HPV53, HPV16 and HPV81. These findings highlighted the importance of understanding the epidemiology of HPV infection in specific populations, such as postmenopausal women in Nanjing, China. The results could provide valuable information for healthcare professionals and policymakers to develop targeted prevention and screening strategies for reducing the burden of HPV-related diseases in this population.

Anti-Melanoma Activity of Single Intratumoral Injection of ZnPc Micelles Mixed With in situ Gel in B16 Bearing Mouse.

Photodynamic therapy (PDT) is a potential treatment strategy for melanoma. As a second-generation photosensitizer, Zinc phthalocyanine (ZnPc) has many advantages for anti-tumor PDTs, such as strong absorption in the red and near infrared regions, high photo and chemical stability, etc. However, ZnPc has a poor water solubility and is apt to aggregate due to the π-π interaction between molecules, which limits its applications. In this study, various solvents and surfactants were screened for dissolving ZnPc and preparing ZnPc@SDC-TPGS micelle and thermosensitive in situ gel. After the cytotoxic effects of thermosensitive gels on PDT were tested, the antitumor effects on PDT of them in mice by intratumoral injection were evaluated, including body weight, and tumor weight, volume and morphology. The cell death pathway and the relationship of reactive oxygen species yield with apoptotic rate of tumor cells induced by ZnPc in situ gel were investigated. The results were that N-methyl-pyrrolidone (NMP) mixed with 2 % SDC and aqueous solution containing 2 % TPGS and 2 % SDC were used to synthesize ZnPc@SDC-TPGS micelle and the thermosensitive in situ gel. The cytotoxic effects of thermosensitive gels showed good tumor suppression of ZnPc@SDC-TPGS in situ gel and no toxicity of the blank gel. Intratumoral injection in situ gel containing 3 µg ZnPc under irradiation demonstrated good tumor inhibition in mice with melanoma. Apoptosis has been established as the primary pathway of cell death, and the production of reactive oxygen species (ROS) plays a crucial role in cellular apoptosis induced by ZnPc@SDC-TPGS in situ gel. In conclusion, the intratumoral injection of ZnPc@SDC-TPGS thermosensitive in situ gel provides a promising local treatment option for melanoma.

The Role of Cystathionine-ß-Synthase, H2S, and miRNA-377 in Hypoxic-Ischemic Encephalopathy: Insights from Human and Animal Studies.

We aimed to investigate the mechanism underlying the roles of miRNA-377, Cystathionine-ß-synthase (CBS), and hydrogen sulfide (H2S) in the development of hypoxic-ischemic encephalopathy (HIE). We investigated the relationship between CBS, H2S, and miR-377 in both humans with HIE and animals with hypoxic-ischemic insult. An animal model of fetal rats with hypoxic-ischemic brain injury was established, and the fetal rats were randomly assigned to control and hypoxic-ischemic groups for 15 min (mild) and 30 min (moderate) groups. Human samples were collected from children diagnosed with HIE. Healthy or non-neurological disease children were selected as the control group. Hematoxylin-eosin (HE) staining, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot were used to conduct this study. Hypoxia-ischemia induced pathological alterations in brain tissue changes were more severe in groups with severe hypoxic insult. miRNA-377 expression levels were upregulated in brain tissue and serum of fetal rats and human samples with HIE compared to controls. Conversely, CBS and H2S expression levels were significantly decreased in both human and animal samples compared to controls. Our findings suggest that CBS is a target gene of miR-377 which may contribute to the development of HIE by regulating CBS/H2S. H2S has a protective effect against hypoxic damage in brain tissue. The study provides new insights into the potential mechanisms underlying the protective role of H2S in hypoxic brain damage and may contribute to the development of novel therapies for HIE.

Krüppel-like factor 12 regulates aging ovarian granulosa cell apoptosis by repressing SPHK1 transcription and sphingosine-1-phosphate (S1P) production.

Oxidative stress triggered by aging, radiation, or inflammation impairs ovarian function by inducing granulosa cell (GC) apoptosis. However, the mechanism inducing GC apoptosis has not been characterized. Here, we found that ovarian GCs from aging patients showed increased oxidative stress, enhanced reactive oxygen species activity, and significantly decreased expression of the known antiapoptotic factor sphingosine-1-phosphate/sphingosine kinase 1 (SPHK1) in GCs. Interestingly, the expression of Krüppel-like factor 12 (KLF12) was significantly increased in the ovarian GCs of aging patients. Furthermore, we determined that KLF12 was significantly upregulated in hydrogen peroxide-treated GCs and a 3-nitropropionic acid-induced in vivo model of ovarian oxidative stress. This phenotype was further confirmed to result from inhibition of SPHK1 by KLF12. Interestingly, when endogenous KLF12 was knocked down, it rescued oxidative stress-induced apoptosis. Meanwhile, supplementation with SPHK1 partially reversed oxidative stress-induced apoptosis. However, this function was lost in SPHK1 with deletion of the binding region to the KLF12 promoter. SPHK1 reversed apoptosis caused by hydrogen peroxide-KLF12 overexpression, a result further confirmed in an in vitro ovarian culture model and an in vivo 3-nitropropionic acid-induced ovarian oxidative stress model. Overall, our study reveals that KLF12 is involved in regulating apoptosis induced by oxidative stress in aging ovarian GCs and that sphingosine-1-phosphate/SPHK1 can rescue GC apoptosis by interacting with KLF12 in negative feedback.

New insights for gynecological cancer therapies: from molecular mechanisms and clinical evidence to future directions.

Advanced and recurrent gynecological cancers lack effective treatment and have poor prognosis. Besides, there is urgent need for conservative treatment for fertility protection of young patients. Therefore, continued efforts are needed to further define underlying therapeutic targets and explore novel targeted strategies. Considerable advancements have been made with new insights into molecular mechanisms on cancer progression and breakthroughs in novel treatment strategies. Herein, we review the research that holds unique novelty and potential translational power to alter the current landscape of gynecological cancers and improve effective treatments. We outline the advent of promising therapies with their targeted biomolecules, including hormone receptor-targeted agents, inhibitors targeting epigenetic regulators, antiangiogenic agents, inhibitors of abnormal signaling pathways, poly (ADP-ribose) polymerase (PARP) inhibitors, agents targeting immune-suppressive regulators, and repurposed existing drugs. We particularly highlight clinical evidence and trace the ongoing clinical trials to investigate the translational value. Taken together, we conduct a thorough review on emerging agents for gynecological cancer treatment and further discuss their potential challenges and future opportunities.

CAFs orchestrates tumor immune microenvironment-A new target in cancer therapy?

Cancer immunotherapy has opened a new landscape in cancer treatment, however, the poor specificity and resistance of most targeted therapeutics have limited their therapeutic efficacy. In recent years, the role of CAFs in immune regulation has been increasingly noted as more evidence has been uncovered regarding the link between cancer-associated fibroblasts (CAFs) and the evolutionary process of tumor progression. CAFs interact with immune cells to shape the tumor immune microenvironment (TIME) that favors malignant tumor progression, a crosstalk process that leads to the failure of cancer immunotherapies. In this review, we outline recent advances in the immunosuppressive function of CAFs, highlight the mechanisms of CAFs-immune cell interactions, and discuss current CAF-targeted therapeutic strategies for future study.

Mitochondrial Transfer from Mouse Adipose-Derived Mesenchymal Stem Cells into Aged Mouse Oocytes.

Due to the decline in the quantity and quality of oocytes related to age, the fertility of women over 35 years of age has declined sharply. The molecular mechanisms that maintain oocyte quality remain unclear, thus it is difficult to increase the birth rate of women over 35 years old at present. Oocytes contain more mitochondria than any type of cell in the body, and any mitochondrial dysfunction can lead to reduced oocyte quality. In the 1990s, oocyte cytoplasmic transfer resulted in great success in human reproduction but was accompanied by ethical controversies. Autologous mitochondrial transplantation is expected to be a useful technique to increase the quality of oocytes that have decreased due to age. In the present study, we used adipose-derived stem cells from aged mice as a mitochondria donor to increase the quality of oocytes of aged mice. Further development of autologous mitochondrial transfer technology will provide a new and effective treatment for infertility in aged women.

Nitrogen removal by Rhodococcus sp. SY24 under linear alkylbenzene sulphonate stress: Carbon source metabolism activity, kinetics, and optimum culture conditions.

Artificial intervention combined with stress acclimation was used to screen a heterotrophic nitrifying-aerobic denitrifying (HN-AD) bacterial, strain Rhodococcus SY24, resistant to linear alkylbenzenesulfonic acid (LAS) stress. When LAS was<15 mg/L, strain SY24 performed better cell growth and carbon source metabolism activity. The maximum nitrification and denitrification rates of SY24 under LAS stress could reach 1.18 mg/L/h and 1.05 mg/L/h, respectively, which were 13.80 % and 8.81 % higher than those of the original strain CPZ24. Higher LAS tolerance was seen in the functional genes (amoA, nxrA, napA, narG, nirK, nirS, norB, and nosZ). Response surface modeling revealed that 2 mg/L LAS, sodium succinate as a carbon source, 190 rams, and carbon/nitrogen 11 were the ideal culture conditions for SY24 to nitrogen removal under the LAS environment. This study offered a new screening strategy for the functional species, and strain SY24 showed significant LAS tolerance and HN-AD potential.

Spatial distribution of bacterial resistance towards antibiotics of rural sanitation system in China and its potential link with diseases incidence.

Chinese government is vigorously promoting toilet renovation in rural areas to reduce the risk of human feces exposure, which would cause infectious diseases, especially antibiotic resistance genes (ARGs) and pathogens. However, the distribution of ARGs in human feces from different regions of China remained ill-defined. It is not yet known how the survival of ARGs after toilet treatment is associated with the regional infection rates. Here, we investigated the prevalence of ARGs in human feces in rural areas of China and their potential relationship with infectious diseases for the first large-scale. The results showed that there were still high ARGs residues in human feces after rural toilet treatment, especially tetM-01 and ermB with average relative abundance as high as 1.21 × 10-1 (Eastern) and 1.56 × 10-1 (Northern), respectively. At a large regional scale, the significant differences in human feces resistomes were mainly shaped by the toilet types, TN, NH3-N, and the bacterial community. A critical finding was that toilets still cannot effectively decrease the pathogenicity risk in human feces. The significant positive relationship (P<0.05) between infectious diseases and ARGs can infer that ARGs in human feces exposure might be a critical path for enhancing the incidence of diseases, as these ARGs hinder the effectiveness of antibiotics.

X-box binding protein 1: A new metabolic mediator and drug target of metformin?

Accumulating evidence has demonstrated that metformin improved hypertriglyceridemia. The present study aim to investigate the molecular mechanism by which metformin improves hypertriglyceridemia via regulation of diacylglycerol O-acyltransferase 2 (DGAT2) and X-box binding protein 1 (XBP1) in the liver and whether AMP-activated protein kinase (AMPK) is involved. Mice were fed a high-fat diet (HFD) or high-fat diet with metformin for 5 weeks to evaluate the effect of metformin on triglyceride (TG) levels and expression of DGAT2 and XBP1 in the liver. In vitro HepG2 cells or XBP1 knockout AML12 hepatocytes were stimulated with metformin, palmitic acid or small interfering RNA inducing XBP1 knockdown, or dominant-negative mutant AMPK plasmid. Metformin treatment reduced hepatic TG levels in the liver of HFD-fed mice. Expression of nuclear and cytoplasmic XBP1 protein and its downstream target gene DGAT2 decreased in the liver of HFD-fed mice and HepG2 cells after metformin treatment. AMPK inactivation or overexpression of XBP1 attenuates this effect. Our preliminary results demonstrate that metformin activates AMPK to reduce TG synthesis by inhibiting the XBP1-mediated DGAT2 pathway, at least in part, suggesting that XBP1 is a new metabolic mediator for metformin treatment of hypertriglyceridemia and associated metabolic disease.

Isolation and Culture of Three Kinds of Umbilical Cord Mesenchymal Stem Cells.

Umbilical cord mesenchymal stem cells (UC-MSCs) are an important cell source for regenerative medicine. UC-MSCs can be isolated from the umbilical cord Wharton's jelly, as well as from the umbilical arteries and umbilical vein. They are known as perivascular stem cells obtained from umbilical arteries (UCA-PSCs), perivascular stem cells obtained from the umbilical vein (UCV-PSCs), and mesenchymal stem cells obtained from Wharton's jelly (WJ-MSCs). UCA-PSCs and UCV-PSCs are pericytes derived from perivascular regions that are progenitors of MSCs. Isolation and culture of the three kinds of cells is an important source for studying stem cell transplantation and repair. The present protocol focuses on the isolation and culture of cells through mechanical separation, adherent culture, and cell crawling out. Through this technique, the three different types of stem cells can be derived. Cell surface markers were detected by flow cytometry. The stem cells were detected for multilineage differentiation potential by adipogenic, osteogenic, and neural-like differentiation, which is consistent with the phenotype of MSCs. This experimental protocol expands the source of UC-MSCs. In addition, the cell isolation method provides a basis for further study of regenerative medicine and other applications.

Full-Scale of a Compost Process Using Swine Manure, Human Feces, and Rice Straw as Feedstock.

Regarding the composting of rural waste, numerous studies either addressed the composting of a single waste component or were conducted at a laboratory/pilot scale. However, far less is known about the mixed composting effect of multi-component rural waste on a large scale. Here, we examined nutrient transformation, maturity degree of decomposition, and succession of microbial communities in large-scale (1,000 kg mixed waste) compost of multi-component wastes previously optimized by response models. The results showed that multi-component compost can achieve the requirement of maturity and exhibit a higher nutritional value in actual compost. It is worth noting that the mixed compost effectively removed pathogenic fungi, in which almost no pathogenic fungi were detected, and only two pathogenic bacteria regrown in the cooling and maturation stages. Structural equation models revealed that the maturity (germination index and the ratio of ammonium to nitrate) of the product was directly influenced by compost properties (electrical conductivity, pH, total organic carbon, moisture, temperature, and total nitrogen) compared with enzymes (cellulase, urease, and polyphenol oxidase) and microbial communities. Moreover, higher contents of total phosphorus, nitrate-nitrogen, and total potassium were conducive to improving compost maturity, whereas relatively lower values of moisture and pH were more advantageous. In addition, compost properties manifested a remarkable indirect effect on maturity by affecting the fungal community (Penicillium and Mycothermus). Collectively, this evidence implies that mixed compost of multi-component rural waste is feasible, and its efficacy can be applied in practical applications. This study provides a solution for the comprehensive treatment and utilization of rural waste.

Adverse impact of elevated progesterone levels on human chorionic gonadotropin trigger day on blastocyst transfer outcomes in gonadotropin-releasing hormone agonist cycles.

OBJECTIVE: Dose an elevated serum progesterone (P) level on the human chorionic gonadotropin (hCG) trigger day have a negative effect on clinical pregnancy outcomes for embryos transferred at different stages of development in long-acting gonadotropin-releasing hormone agonist (GnRHa) in vitro fertilization-embryo transfer (IVF-ET) cycles? STUDY DESIGN: This was a noninterventional, retrospective, observational, single-centre cohort study. A total of 1951 patients received long-acting GnRHa for pituitary downregulation in IVF-ET cycles at Nanjing Drum Tower Hospital from January 2018 to December 2020. The serum P levels on the day of hCG administration were measured, together with other cycle parameters, to explore the relationship between P levels and the clinical pregnancy rate (CPR) of different embryos transferred. RESULTS: When the serum P level on the hCG day was higher than 1.5 ng/mL, the CPR did not decrease significantly. There was no correlation between the CPR of cleavage-stage embryo transfer and the serum P level on the hCG day. In addition, the interaction analysis suggested that the CPR of patients undergoing blastocyst transfer decreased as serum P levels on the hCG day increased. Progesterone levels on the day of hCG administration were closely related to the CPR of blastocyst transfer rather than cleavage-stage embryo transfer. CONCLUSION: An increased serum P level on the day of hCG administration did not affect the CPR of cleavage-stage embryo transfer, but it reduced the CPR of blastocyst transfer cycles.