The interplay of singlet oxygen and ABI4 in plant growth regulation.

Abscisic acid (ABA) and the AP2/ERF (APETALA 2/ETHYLENE-RESPONSIVE FACTOR)-type transcription factor ABA INSENSITIVE 4 (ABI4) control plant growth and development. We review how singlet oxygen, which is produced in chloroplasts of the fluorescent mutant of Arabidopsis thaliana (arabidopsis), and ABI4 may cooperate in transcriptional and translational reprogramming to cause plants to halt growth or demise. Key elements of singlet oxygen- and ABI4-dependent chloroplast-to-nucleus retrograde signaling involve the chloroplast EXECUTER (EX) 1 and EX2 proteins as well as nuclear WRKY transcription factors. Mutants designed to study singlet oxygen signaling, that lack either ABI4 or the EX1 and EX2 proteins, do not show most of the growth effects of singlet oxygen. We propose a model that positions ABI4 downstream of WRKY transcription factors and EX1 and EX2.

Predictive Value of Esophageal Deviation Index for Clinical Outcomes of Patients With Left-Sided Congenital Diaphragmatic Hernia.

PURPOSE: This study aimed to evaluate the prognostic value of postnatal esophageal deviation index (EDI) measured within the first 24 h of life for predicting mortality and morbidity in neonates with left-sided congenital diaphragmatic hernia (L-CDH). METHOD: This retrospective study analyzed clinical data from 133 neonates with L-CDH admitted to Guangzhou Women and Children's Medical Center between January 2016 and January 2024. Patients were categorized into two groups based on outcomes: survivors (n = 108) and non-survivors (n = 27). Risk factors for mortality were identified using both univariate and multivariate analyses. A receiver operating characteristic (ROC) curve was utilized to evaluate the predictive value of EDI for mortality in L-CDH patients. Subsequently, patients were divided into two groups: those with an EDI> 16.1% and those with an EDI≤16.1%. The relationship between EDI and both mortality and morbidity was analyzed using Kaplan-Meier analysis, chi-square test, Fisher's exact test, and multivariate analysis. RESULTS: EDI (adjusted OR: 0.822, 95% CI 0.723-0.935; P = 0.003) was identified as the independent predictor of mortality through both univariate and multivariate logistic regression analysis. The ROC curve demonstrated that the area under the curve (AUC) for predicting the mortality was 0.854 (95%CI: 0.782-0.930) for EDI, with an optimal cut-off value of 16.125%. The cumulative mortality rate through Day 200 was higher in patients with an EDI>16.1% (P＜0.001). Among the 133 neonates with L-CDH, 24.8% had an EDI>16.1%. This was associated with significantly worse CDH characteristics, including a high incidence of intrathoracic stomach and a high occurrence of high-risk defect sizes (type C/D), (P＜0.001), as well as more severe pulmonary hypertension (P＜0.001). An EDI>16.1% was associated with higher mortality and a greater need for ECMO support compared to an EDI≤16.1% (P＜0.001). CONCLUSION: EDI within the first 24 h of life in patients with L-CDH is associated with increased mortality and the need for ECMO, particularly when EDI exceeds 16.1%. LEVEL OF EVIDENCE: III.

Exploring the relationship between lignin structure and antioxidant property using lignin model compounds.

Lignin has a natural polyphenol structure that is expected to replace chemically synthesized antioxidants as a native antioxidant with biodegradable and convenient source characteristics. However, the improvement of the antioxidant property of lignin and its application as an antioxidant are still somewhat limited due to the lack of understanding of the relationship between specific lignin structures and antioxidant property. Therefore, the study of the relationship between lignin structure and antioxidant property is crucial to realize the high-quality application of lignin. In this experiment, the scavenging ability of free 1,1-diphenyl-2-picrylhydrazyl (DPPH·) radicals was determined for different grades of acetylated tannins, typical lignin model compounds and different structural units of milled wood lignin to investigate the relationship between lignin structure and antioxidant property. Based on the experimental results, some structure-activity relationships were proposed and the mechanism of the antioxidant property of lignin was discussed. The number of phenolic hydroxyl groups was linearly and positively correlated with antioxidant property, and the scavenging of DPPH radicals increased significantly with the increase in the number of methoxy groups in the model compounds. Moreover, aldehyde and carboxyl groups had a negative effect on the antioxidant property of lignin, while methoxy, alkyl and alcohol hydroxyl groups played a positive role. The guaiacyl (G) and syringyl (S) units favored the antioxidant property, so the difference in the content of structural units in lignin under certain conditions of phenolic hydroxyl content also affected the antioxidant property. Therefore, the antioxidant property of aspen milled lignin was higher than that of other milled lignin from different wood species. Finally, the mechanism of DPPH free radical scavenging by lignin was revealed to better understand the relationship between lignin structure and antioxidant property.

Enhanced Safety and Efficacy of O-Arm Navigation Over C-Arm Guidance in Percutaneous Kyphoplasty for Patients With Osteoporotic Vertebral Compression Fractures and Spinal Deformity: A Comparative Study.

OBJECTIVE: Although percutaneous kyphoplasty (PKP) under C-arm guidance is an effective treatment for osteoporotic vertebral compression fractures (OVCF), obtaining high-definition images in patients with OVCF and spinal deformities can be challenging or insufficient using traditional C-arm guidance, prompting our institution to adopt the O-arm navigation system-which offers comprehensive 3D imaging and precise navigation-and this study compares its safety and efficacy with conventional C-arm-assisted PKP. METHODS: This was a retrospective study. From February 2019 to February 2022, we enrolled 28 patients with OVCF (44 vertebrae) with spinal deformity treated with O-arm navigation-assisted PKP and 30 patients with OVCF (42 vertebrae) with spinal deformity treated with C-arm-guided PKP. We recorded puncture times, single-segment operation time, number of cases with bone cement leakage, and length of stay. The visual analog scales (VASs), Oswestry disability indexes (ODIs), recovery of Cobbs angle, and vertebral height were used to assess treatment effect before the operation, on the first day postoperation, the first month postoperation, and at the final follow-up. The chi-squared test was utilized for comparing discrete variables, an independent samples t-test was used for continuous variables, and Pearson's chi-squared test and Fisher's exact test were applied for categorical data. RESULTS: Demographic features were comparable between the groups. The O-arm navigation group showed a significant reduction in puncture adjustment per vertebrae, single-segment operation time, and the rate of trocar needle malposition compared to the C-arm guidance group. The rate of cement leakage was decreased in the O-arm-guided PKP group, and other complications did not differ between the two groups. Intragroup comparisons revealed significant improvements in VAS scores and ODI on the first day, first month, and final follow-up after the operation (p < 0.05). The VAS score was significantly lower in the O-arm navigation-assisted PKP group than in the C-arm-guided PKP group on the first day postoperatively (p = 0.049). However, no significant differences in VAS scores were observed between the groups at the first month postoperatively or at the final follow-up. In each follow-up period, there was no significant difference in ODI, Cobb angle, and the percent of anterior vertebral height (AVH %) between the groups. CONCLUSION: O-arm navigation-assisted PKP demonstrates better clinical safety and efficacy than C-arm-guided PKP, marking it as a minimally invasive, safe, and effective procedure for treating patients with OVCF with spinal deformity.

Advances in the Study of the Pathogenesis of Vogt-Koyanagi-Harada Syndrome.

Vogt-Koyanagi-Harada syndrome (VKHS) is a common type of uveitis characterized by the invasion of melanocyte-rich tissues. In recent years, the incidence of VKHS has been increasing yearly, and its specific pathogenesis has not yet been elucidated. However, its pathogenesis has been a hot topic of research. The clinical course of VKHS is characterized by the early involvement of the posterior segment of the eye, including exudative retinal detachment, optic papillitis, bilateral diffuse chorioretinitis, etc. If treated improperly or with delayed treatment, the inflammation may gradually spread to the anterior segment of the eye, leading to vision loss or even vision. This study examines the pathogenesis of VKHS. It reviews the progress of research on the pathogenesis of VKHS, which will help to improve the understanding of VKHS and provide a reference for subsequent studies.

Discovery of Enantiopure (S)-Methoprene Derivatives as Potent Biochemical Pesticide Candidates.

(S)-Methoprene has been widely applied as a powerful biochemical pesticide to control disease vectors and other pestiferous arthropods of economic importance. As a juvenile hormone analogue, many products based on (S)-methoprene are developed and commercialized in the USA, Europe, and elsewhere. However, the agricultural use of (S)-methoprene and its analogues remains underexplored. Here, based on an intermediate derivatization strategy and structural modification, a series of enantiopure (S)-methoprene derivatives were designed for their expected bioactivity against two crop-threatening pests. Six compounds showed more than 2-fold stronger inhibition of emergence against Plutella xylostella than (S)-methoprene, among which one that was designated as B2 showed even superior activity to the conventional chemical pesticide and biopesticide with IE50 of 0.02 mg/L. Nine compounds exhibited over 2-fold higher bioactivity against Aphis craccivora growth than (S)-methoprene. The physicochemical property evaluation and toxicological test showed that the potent (S)-methoprene derivatives were low toxic to the nontarget organism and the environment. Molecular docking studies further demonstrated that the high bioactivity of B2 may be partially attributed to its great affinity for binding to juvenile hormone receptors of P. xylostella. The current study suggests that B2 is a biochemical pesticide candidate with potency to be developed as a new agrochemical for lepidopteran control.

Feasibility of fractal dimension analysis for left ventricular trabecular complexity using cardiac computed tomography.

AIMS: To evaluate the consistency between fractal dimensions (FD) derived from cardiac computed tomography (CT-FD) and cardiac magnetic resonance (MR-FD) in assessing left ventricular trabecular complexity. METHODS: This retrospective study included 170 patients who underwent CCT and CMR scans within two weeks. Five short-axis cine images were selected at end-diastole: one basal, three mid, and one apical slice. Short-axis CCT views were reconstructed and aligned with the cine images. CT-FD and MR-FD values were calculated for each slice, with mean values determined for each patient. Severe left ventricular hypertrophy (LVH) was defined as a maximum wall thickness > 15 mm in end-diastolic cine images. RESULTS: The diastolic CT-FD and MR-FD values exhibited high consistency, with values of 1.253 ± 0.091 and 1.250 ± 0.102, respectively (n = 535, ICC = 0.882, 95 % CI: 0.861-0.899, P < 0.001). Similarly, the systolic CT-FD and MR-FD values demonstrated good consistency, with values of 1.268 ± 0.072 and 1.286 ± 0.093, respectively (n = 390, ICC = 0.720, 95 % CI: 0.669-0.765, P < 0.001). For subgroups of systolic NLVH and LVH, the ICCs were 0.773 (n = 305, CI: 0.723-0.814, P < 0.001) and 0.565 (n = 85, 95 % CI: 0.402-0.694, P < 0.001), respectively. The diagnostic efficacy of mean CT-FD aligned with that of mean MR-FD in distinguishing abnormal cardiac conditions from the CMR-negative group. CONCLUSIONS: CCT is a feasible method for assessing left ventricular trabecular complexity, with good agreement with CMR, except in cases of severe left ventricular hypertrophy during systole.

BLNK negatively regulates innate antifungal immunity through inhibiting c-Cbl-mediated macrophage migration.

B cell linker protein (BLNK) is crucial for orchestrating B cell receptor-associated spleen tyrosine kinase (Syk) signaling. However, the role of BLNK in Syk-coupled C-type lectin receptor (CLR) signaling in macrophages remains unclear. Here, we delineate that CLRs govern the Syk-mediated activation of BLNK, thereby impeding macrophage migration by disrupting podosome ring formation upon stimulation with fungal ß-glucans or α-mannans. Mechanistically, BLNK instigates its association with casitas B-lineage lymphoma (c-Cbl), competitively impeding the interaction between c-Cbl and Src-family kinase Fyn. This interference disrupts Fyn-mediated phosphorylation of c-Cbl and subsequent c-Cbl-associated F-actin assembly. Consequently, BLNK deficiency intensifies CLR-mediated recruitment of the c-Cbl/phosphatidylinositol 3-kinase complex to the F-actin cytoskeleton, thereby enhancing macrophage migration. Notably, mice with monocyte-specific BLNK deficiency exhibit heightened resistance to infection with Candida albicans, a prominent human fungal pathogen. This resistance is attributed to the increased infiltration of Ly6C+ macrophages into renal tissue. These findings unveil a previously unrecognized role of BLNK for the negative regulation of macrophage migration through inhibiting CLR-mediated podosome ring formation during fungal infections.

Characterization of renal injury in non-squamous non-small cell lung cancer patients treated with pemetrexed: A single-center retrospective study.

INTRODUCTION: Pemetrexed is a key therapeutic agent for advanced non-squamous non-small cell lung cancer (Nsq-NSCLC), yet it is associated with renal toxicity. This study aims to elucidate the incidence, risk factors, and survival impact of renal injury in patients with Nsq-NSCLC treated with pemetrexed. METHODS: We conducted a retrospective study including 136 patients with Nsq-NSCLC treated with pemetrexed. Data on demographics, renal function, progression-free survival (PFS), and overall survival (OS) were collected. Renal injury was defined as a reduction above 25% in estimated glomerular filtration rate (eGFR) from baseline. Its associated risk factors were analyzed using logistic regression, and impact on survival was analyzed using log-rank test. The creatinine clearance rate (CCr) was calculated, and a CCr < 45 mL/min served as a contraindication for continuing pemetrexed. RESULTS: The study found a 31.6% (43/136) incidence of renal injury, with 9.6% (13/136) having CCr < 45 mL/min and discontinuing pemetrexed. Univariate and multivariate analyses identified factors significantly associated with increased renal injury risk including older age, use of cisplatin, and higher number of pemetrexed cycles. The patients with renal injury had a median PFS (mPFS) of 13.5 months and a median OS (mOS) of 36.0 months, while the patients without had an mPFS of 9.0 months and an mOS of 35.0 months, and these differences were not statistically significant. CONCLUSION: Renal injury is a considerable complication in patients with Nsq-NSCLC undergoing pemetrexed treatment, with age, platinum type, and pemetrexed treatment cycles as key risk factors. These findings highlight the necessity for careful renal monitoring in this patient population.

DAB2 + macrophages support FAP + fibroblasts in shaping tumor barrier and inducing poor clinical outcomes in liver cancer.

Background: Cancer-associated fibroblasts (CAFs) are the key components of the immune barrier in liver cancer. Therefore, gaining a deeper understanding of the heterogeneity and intercellular communication of CAFs holds utmost importance in boosting immunotherapy effectiveness and improving clinical outcomes. Methods: A comprehensive analysis by combing single-cell, bulk, and spatial transcriptome profiling with multiplexed immunofluorescence was conducted to unravel the complexities of CAFs in liver cancer. Results: Through an integrated approach involving 235 liver cancer scRNA-seq samples encompassing over 1.2 million cells, we found that CAFs were particularly increased in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). FAP + fibroblasts were identified as the dominant subtype of CAFs, and which were mainly involved in extracellular matrix organization and angiogenesis. These CAFs were enriched in the tumor boundary of HCC, but diffusely scattered within ICC. The DAB2 + and SPP1 + tumor-associated macrophages (TAMs) reinforce the function of FAP + CAFs through signals such as TGF-ß, PDGF, and ADM. Notably, the interaction between DAB2 + TAMs and FAP + CAFs promoted the formation of immune barrier and correlated with poorer patient survival, non-response to immunotherapy in HCC. High FAP and DAB2 immunohistochemical scores predicted shorter survival and higher serum AFP concentration in a local clinical cohort of 90 HCC patients. Furthermore, this communication pattern might be applicable to other solid malignancies as well. Conclusions: The interaction between DAB2 + TAMs and FAP + CAFs appears crucial in shaping the immune barrier. Strategies aimed at disrupting this communication or inhibiting the functions of FAP + CAFs could potentially enhance immunotherapy effectiveness and improve clinical outcomes.

The gut microbiota improves reproductive dysfunction in obese mice by suppressing the NLRP3/ASC/caspase-1 axis.

Aim: To explore the complex relationship between gut microbiota, obesity-related male reproductive impairments, and the NLRP3 inflammasome.Methods: A high-fat diet was administered to induce obesity in a mouse model, fecal microbiota transplantation or a high-dietary fiber diet (HDFD) was administered for 5 weeks to evaluate changes in parameters related to reproductive capacity, NLRP3, gut microbiota composition and metabolites in mice.Results: A high-fat diet induces obesity and decreases reproductive capacity in male mice. Fecal microbiota transplantation and HDFD can improve reproductive capacity in obese mice by adjusting the gut microbiota population to suppress the NLRP3/ASC/caspase-1 axis, thereby reducing IL-1ß levels.Conclusion: This study offers a potential treatment for obesity-induced reproductive dysfunction by targeting the gut microbiota and the NLRP3 inflammasome pathway.

This study looks at how gut bacteria, obesity and our immune system affect male reproductive health. We made mice obese by feeding them a high-fat diet. Then, we treated them with either a transplant of gut bacteria or a high-fiber diet for 5 weeks. We found that the high-fat diet made it harder for male mice to have babies. Both the transplant and the high-fiber diet helped improve their ability to reproduce. Changing the bacteria in their gut reduced inflammation by affecting the immune system. Our findings suggest that changing gut bacteria and focusing on this part of the immune system could help with reproductive problems caused by obesity.

Effect of remimazolam on intra-operative hypotension: Systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Hypotension is common during anaesthesia. Increasing number of studies have reported that remimazolam may be associated with lower incidence of intra-operative hypotension compared with other anaesthetics. However, the results remain controversial. OBJECTIVE: This study aimed to evaluate the influence of remimazolam on intra-operative hypotension and its related outcomes (hypoxaemia, bradycardia and time to awake). DESIGN: A systematic review of randomised controlled trials (RCTs) with meta-analyses. DATA SOURCES: PubMed, Cocharane and Embase databases were searched to identify eligible RCTs published up to June 2024. ELIGIBILITY CRITERIA: RCTs published in English were eligible for inclusion. The study patients were 18 years or older who were administered with remimazolam and other positive control agents in either the pre-operative or intra-operative period. The incidence of intra-operative hypotension was identified in these studies. RESULTS: This study evaluated 34 trials including 4847 individuals. Basing on moderate-certainty evidence, we found that remimazolam administration reduced the incidence of intra-operative hypotension [risk ratio (RR) = 0.48, 95% confidence interval (95% CI): 0.41 to 0.57] and bradycardia (16 studies, n  = 2869, RR = 0.40, 95% CI: 0.29 to 0.54). No difference was observed in the incidence of hypoxaemia (RR = 0.70, 95% CI: 0.48 to 1.01) and time to awake (MD = -0.91, 95% CI: -2.42 to 0.60). The remarkable association between remimazolam and hypotension remained robust and significant, regardless of general anaesthesia or procedural sedation ( P  < 0.01, I2  = 82%). No significant difference was found between different control drugs ( P  = 0.97, I2  = 82%). CONCLUSION: Moderate-quality evidence shows that remimazolam administration to patients undergoing general anaesthesia or procedural sedation decreases the incidence of intra-operative hypotension and bradycardia.

Genetic association of GJA8 with long-segment Hirschsprung's disease in southern Chinese children.

Background: Hirschsprung's disease (HSCR) is a complex congenital neurodevelopmental disorder affecting colons caused by both genetic and environmental factors. Although several genes have been identified as contributing factors in HSCR, the pathogenesis is still largely unclear, especially for the low prevalent long-segment HSCR (L-HSCR). Gap junction protein alpha 8 (GJA8) is involved in several physiological processes and has been implicated in several diseases. However, the relationship between GJA8 single nucleotide polymorphism (SNP) rs17160783 and HSCR in the southern Chinese population remains unknown. The study aimed to explore the association of genetic variants in GJA8 and HSCR susceptibility in southern Chinese. Methods: SNP rs17160783 A>G in GJA8 was genotyped by TaqMan SNP Genotyping Assay in all samples, which included 1,329 HSCR children (cases) and 1,473 healthy children (controls). Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association of GJA8 polymorphisms with HSCR susceptibility. The GTEx database and transcription factor binding site (TFBS) prediction were used to analyze the potential regulatory function of rs17160783. Results: Genetic association analysis illustrated that rs17160783 could increase the risk of L-HSCR (Padj=0.04, ORadj =1.48, 95% CI: 1.02-2.14). We also found that GJA8 expression was increased in HSCR and neurodevelopmentally impaired animal models. External epigenetic data revealed that GJA8 rs17160783 may have the potential to regulate the expression of the GJA8, possibly by altering the binding of transcription factors for GJA8, and consequently impacting the PI3K-Akt signaling pathway during the enteric nervous system (ENS) development. Conclusions: Our results suggested that rs17160783 might play a regulatory role in GJA8 expression and increase the susceptibility of L-HSCR in children from southern China.

Remarkable pathological response to neoadjuvant tepotinib in lung adenocarcinoma with MET exon 14 skipping mutation: A case report.

Mesenchymal-epithelial transition (MET) exon 14 (METex14) skipping mutation is a rare (3%-4%) driver mutation in non-small cell lung cancer (NSCLC). Tepotinib, a selective MET inhibitor, has shown promise in treating METex14 skipping-mutated NSCLC. However, its feasibility for perioperative application remains unclear. This report describes a 60-year-old man with stage IIIA (cT2N2M0) lung adenocarcinoma harboring a METex14 skipping mutation. After initial treatment with savolitinib was discontinued due to grade 4 transaminitis, the patient was switched to tepotinib, resulting in significant tumor regression. Six months later, further shrinkage was observed, and surgery revealed remarkable pathological response with no residual tumor in lymph nodes (ypT2N0M0, IB). Postoperative tepotinib continued, with no relapse at 6-month follow-up. This case highlights the potential of tepotinib as neoadjuvant therapy for resectable METex14 skipping-mutated NSCLC, warranting further clinical trials.

Current Progress and Challenges in the Development of Pharmacotherapy for Metabolic Dysfunction-Associated Steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH), a severe form of metabolic dysfunction-associated steatotic liver disease (MASLD), poses a significant threat to global health. Despite extensive research efforts over the past decade, only one drug has received market approval under accelerated pathways. In this review, we summarise the pathogenesis of MASH and present a comprehensive overview of recent advances in phase 2-3 clinical trials targeting MASH. These trials have highlighted considerable challenges, including low response rates to drugs, limitations of current surrogate histological endpoints, and inadequacies in the design of MASH clinical trials, all of which hinder the progress of MASH pharmacotherapy. We also explored the potential of non-invasive tests to enhance clinical trial design. Furthermore, given the strong association between MASLD and cardiometabolic disorders, we advocate for an integrated approach to disease management to improve overall patient outcomes. Continued investigation into the mechanisms and pharmacology of combination therapies may offer valuable insights for developing innovative MASH treatments.

Building a Tailored Frame-Channel Structure for High-Performance Protein Air Filters.

To create a healthier indoor environment via sustainable technologies, there is a growing demand for constructing high-performance air filters from natural materials. Addressing this need, we have fabricated high-performance protein air filters with a tailored frame-channel structure via electrospinning. The innovative feature of the protein air filter is generated by adding a small amount of an organic salt, tetrabutylammonium chloride (TBAC), to modulate the denaturation of zein for tuning electrical charge distribution and hydrophilicity of the protein solutions. The results highlight that the optimized filter with 1.0 wt% TBAC exhibits a denser nanofiber assembly on the frame and a sparser arrangement on the channel. Functionally, the filter demonstrates ultralow pressure drop (ca. 9.04 Pa) that is only a third of that observed in unmodified formulation and commercial air filters, while it maintains high filtration efficiency in capturing PM2.5 (99.42% ± 0.30%) and PM0.3 (98.25 ± 0.39%). More importantly, the filter indicates multifunctional perspectives, e.g., high removal efficiency for formaldehyde (HCHO) and PM2.5 under high airflow rates (up to 8 L/min) or after prolonged testing period (120 min). Our design of the frame-channel structure for the protein air filter marks a leap forward in developing biomass-based structural materials.

[Advances in bitterness receptors T2Rs in different diseases].

Bitterness, as one of the most important physiological sensations in animals, is primarily recognized through the mediation of bitter taste receptors. In recent years, it has been found that these receptors are not only expressed in taste bud cells on the tongue but also in the respiratory, cardiovascular, digestive, reproductive, and nervous systems. They are involved in regulating various fundamental physiological processes and are now considered important targets for the treatment of various diseases. This paper reviewed the structure, classification, distribution, and signaling pathways of bitter taste receptors, their relationship with different diseases, and the role of bitter taste receptors agonists, aiming to provide a basis for scientific research on bitter taste receptors.

The Causal Relationship Between Immune Cells and Infertility: A Mendelian Randomisation Study.

OBJECTIVE: Infertility has emerged as a significant global public health concern, with a multitude of complex underlying causes. Epidemiological evidence indicates that immunological factors are significant contributors to the aetiology of infertility. However, previous studies on the relationship between immune inflammation and infertility have yielded inconclusive results. METHODS: Mendelian randomisation (MR) is an emerging statistical method that employs exposure-related genetic variation as an instrumental variable (IV) to infer causal relationships between immune cells and infertility by modelling the principle of random assignment in Mendelian genetics. In this study, MR was employed to assess the causal relationship between 731 immune cell signatures and infertility. The data utilized in this study were obtained from publicly available genome-wide association studies (GWAS) and validated IVs, which were employed to fulfil the essential assumptions of MR analysis. RESULTS: The Mendelian randomisation analysis revealed a total of 27 statistically significant immune cell phenotypes out of 731. The risk factor with the largest odds ratio (OR) was CD28- CD25++ CD8+ %T cell [OR, 1.21; 95% confidence interval (CI), 1.04-1.42], while the protective factor with the largest OR was activated and resting Treg AC (OR, 0.89; 95% CI, 0.82-0.97). CONCLUSION: The present study has demonstrated a correlation between certain characteristics of immune cells and female infertility. These results provide clues for further research into the immune mechanisms of infertility and may inform the development of novel therapeutic strategies.

H-Bond Donor-Directed Switch of Diastereoselectivity in the Enantioselective Intramolecular Aza-Henry Reaction of Ketimines.

We report an H-bond donor controlled diastereoselective switchable intramolecular aza-Henry reaction of ketimines derived from α-ketoesters and 2-(2-nitroethyl)anilines, allowing facile access to chiral tetrahydroquinolines bearing an aza-quaternary carbon stereocenter, which are privileged scaffold for medicinal researches. While newly developed cinchona alkaloid derived phosphoramide-bearing quaternary ammonium salt C2 selectively give cis-adducts in up to 20 : 1 dr and 99 % ee, the corresponding urea-bearing analogue C8 preferentially give trans-adducts in up to 20 : 1 dr and 99 % ee.