Exploring the link between obesity and hypothyroidism in autoimmune thyroid diseases: a metabolic perspective.

Background: The management of primary hypothyroidism demands a comprehensive approach that encompasses both the implications of autoimmune thyroid disease and the distinct effects posed by obesity and metabolic irregularities. Despite its clinical importance, the interplay between obesity and hypothyroidism, especially in the context of metabolic perspectives, is insufficiently explored in existing research. This study endeavors to classify hypothyroidism by considering the presence of autoimmune thyroid disease and to examine its correlation with various metabolic obesity phenotypes. Method: This research was conducted by analyzing data from 1,170 individuals enrolled in the Thyroid Disease Database of Shandong Provincial Hospital. We assessed four distinct metabolic health statuses among the participants: Metabolically Healthy No Obese Metabolically Healthy Obese Metabolically Unhealthy No Obese and Metabolically Unhealthy Obese Utilizing logistic regression, we investigated the association between various metabolic obesity phenotypes and hypothyroidism. Results: The study revealed a significant correlation between the Metabolically Unhealthy Obese (MUO) phenotype and hypothyroidism, particularly among women who do not have thyroid autoimmunity. Notably, the Metabolically Unhealthy No Obese (MUNO) phenotype showed a significant association with hypothyroidism in individuals with thyroid autoimmunity, with a pronounced prevalence in women. Furthermore, elevated levels of triglycerides and blood glucose were found to be significantly associated with hypothyroidism in men with thyroid autoimmunity and in women without thyroid autoimmunity. Conclusion: Effective treatment of hypothyroidism requires a thorough understanding of the process of thyroid autoimmune development. In patients without concurrent thyroid autoimmunity, there is a notable correlation between obesity and metabolic issues with reduced thyroid function. Conversely, for patients with thyroid autoimmunity, a focused approach on managing metabolic abnormalities, especially triglyceride levels, is crucial.

Hepatic selective insulin resistance at the intersection of insulin signaling and metabolic dysfunction-associated steatotic liver disease.

Insulin resistance (IR) is a major pathogenic factor in the progression of MASLD. In the liver, insulin suppresses gluconeogenesis and enhances de novo lipogenesis (DNL). During IR, there is a defect in insulin-mediated suppression of gluconeogenesis, but an unrestrained increase in hepatic lipogenesis persists. The mechanism of increased hepatic steatosis in IR is unclear and remains controversial. The key discrepancy is whether insulin retains its ability to directly regulate hepatic lipogenesis. Blocking insulin/IRS/AKT signaling reduces liver lipid deposition in IR, suggesting insulin can still regulate lipid metabolism; hepatic glucose metabolism that bypasses insulin's action may contribute to lipogenesis; and due to peripheral IR, other tissues are likely to impact liver lipid deposition. We here review the current understanding of insulin's action in governing different aspects of hepatic lipid metabolism under normal and IR states, with the purpose of highlighting the essential issues that remain unsettled.

Whole-Genome Resequencing-Based Qualitative Trait Locus Mapping Correlated yellow with the Mutant Color in Honeybees, Apis cerana cerana.

The honeybee, Apis cerana cerana (Ac), is an important pollinator and has adapted to the local ecological environment with relevant coloration. The cuticle coloration of the brown (br) mutant is brown instead of black in wild-type individuals. Therefore, this study aimed to identify and characterize the gene responsible for the br mutation. Genome resequencing with allele segregation measurement using Euclidean distance followed by Lowess regression analysis revealed that the color locus linked to the mutation was located on chromosome 11. A 2-base deletion on exon 4 was identified in the g7628 (yellow) gene after genome assembly and sequence cloning. In addition, the cuticle color of the abdomen of worker bees changed from black to brown when a defect was induced in the yellow gene using short interfering RNA (siRNA); however, the survival rate did not decrease significantly. These results indicate that the yellow gene participated in the body pigmentation, and its defect was responsible for the br mutation. This study promotes the understanding of the molecular basis of body coloration in honeybees, enriching the molecular mechanisms underlying insect pigmentation.

Association Between Monocyte-to-High-Density Lipoprotein Ratio and Prediabetes: A Cross-Sectional Study in Chinese Population.

Background: The monocyte-to-high-density lipoprotein cholesterol (MHR) ratio has been linked to metabolic disorders. However, there is limited research on the predisposition to MHR and prediabetes. Hence, we conducted a study to investigate the relationship between MHR and the prevalence of prediabetes. Methods: In total, 85,293 participants were included in our cross-sectional observational study. Multivariable regression analysis, subgroup analyses, and interaction testing were used to determine the relationship between MHR and prediabetes. To explore the non-linear association of MHR with prediabetes risk, generalized additive model (GAM) and smoothing splines were applied. The threshold effect analysis of MHR on the risk of prediabetes was further employed to identify the turning point. Results: After controlling for covariates, the results indicated that a positive correlation persisted between MHR and prediabetes (odds ratio (OR) =1.64, 95% confidence interval (CI), 1.48-1.82), and subgroup analyses found a more robust correlation between MHR and prediabetes in individuals with lower age, SBP, DBP, TG, TC and higher values of BMI and LDL-C than in their counterparts. Additionally, the correlation between MHR and the risk of prediabetes was found to be non-linear, with a turning point of -0.4 (Log-Likelihood Ratio, P< 0.001). The impact of variables on the two sides of the turning point were 1.94 (1.72, 2.19) and 0.88 (0.69, 1.14). Conclusion: The positive correlation between MHR and the risk of prediabetes in Chinese participants was observed to be non-linear, and MHR ≤ -0.4 was strongly positively correlated with prediabetes risk.

Antibiotic exposure associated with nighttime sleep duration and daytime sleepiness in newlyweds.

Few studies have explored the relationship between antibiotic exposure and sleep in newlyweds. We applied the actor-partner interdependence moderation model to estimate the relationships of antibiotic exposure with nighttime sleep duration (weekday, weekend, and average sleep durations) and daytime sleepiness in newlyweds. We found that 99.0% of the 2698 enrolled individuals were exposed to at least one antibiotic. Among the newlyweds, exposure to florfenicol (ß, - 0.077; 95% confidence interval [CI], - 0.143, - 0.011), exposure to chloramphenicols (- 0.086 [- 0.160, - 0.011]), and exposure to veterinary antibiotics (VAs) (- 0.106 [- 0.201, - 0.010]) were negatively associated with weekday sleep duration. Florfenicol, chloramphenicols, and VAs were also inversely related to average sleep duration in the newlyweds. Ciprofloxacin and cyadox exposure was significantly associated with an increase of 0.264 (0.030, 0.497) and (0.375 [0.088, 0.663]) Epworth Sleepiness Scale (ESS) scores in the newlyweds, respectively. Gender moderated the actor-partner effects of erythromycin and tetracyclines on the newlyweds' weekday sleep duration and ESS scores. Overall, exposure to florfenicol, chloramphenicols, and VAs shortened weekday and average sleep durations of newlyweds. Exposure to ciprofloxacin and cyadox promoted daytime sleepiness. Gender moderated the actor-partner effects of specific antibiotics on the weekday sleep duration and ESS scores of the newlyweds.

The classification of obesity based on metabolic status redefines the readmission of non-Hodgkin's lymphoma-an observational study.

BACKGROUND: The relationship between obesity and non-Hodgkin's lymphoma (NHL) was controversial, which may be due to the crudeness definition of obesity based on body mass index (BMI). As obesity and metabolic abnormalities often coexist, we aimed to explore whether the classification of obesity based on metabolic status can help to evaluate the real impact of obesity on the readmission of NHL. METHODS: In this retrospective cohort study, utilizing the 2018 Nationwide Readmissions Database, we identified NHL-related index hospitalizations and followed them for non-elective readmission. The patients with NHL were classified as metabolically healthy non-obese (MHNO) and obese (MHO) and metabolically unhealthy non-obese (MUNO) and obese (MUO). Readmission rates for each phenotype were calculated at 30-day intervals. Multiple COX regression was used to analyze the association of metabolic-defined obesity with 30-day, 90-day, and 180-day readmission rates in patients with NHL. RESULTS: There were 22,086 index hospitalizations with NHL included. In the multivariate COX regression, MUNO was associated with increased 30-day (HR = 1.113, 95% CI 1.036-1.195), 90-day (HR = 1.148, 95% CI 1.087-1.213), and 180-day readmission rates (HR = 1.132, 95% CI 1.077-1.189), and MUO was associated with increased 30-day (HR=1.219, 95% CI: 1.081-1.374), 90-day (HR = 1.228, 95% CI 1.118-1.348), and 180-day readmission rates (HR = 1.223, 95% CI 1.124-1.33), while MHO had no associations with readmission rates. CONCLUSIONS: The presence of metabolic abnormalities with or without obesity increased the risk of non-selective readmission in patients with NHL. However, obesity alone had no associations with the risk of non-selective readmission, suggesting that interventions for metabolic abnormalities may be more important in reducing readmissions of NHL patients.

The short- and long-term readmission of four major categories of digestive system cancers: does obesity or metabolic disorder matter?

Purpose: Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective cohort study to assess the association between metabolic obesity phenotypes and readmission risks of DSC. Experimental design: A total of 142,753 and 74,566 patients at index hospitalization were ultimately selected from the Nationwide Readmissions Database (NRD) 2018 to establish the 30-day and 180-day readmission cohorts, respectively. The study population was classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Multivariate Cox regression analysis was used to estimate the effect of metabolic obesity phenotypes on DSC readmission. Results: The MUNO phenotype had 1.147-fold (95% CI: 1.066, 1.235; p < 0.001) increased 180-day readmission risks in patients with neoplasm of the upper digestive tract. The MUNO phenotype had 1.073-fold (95% CI: 1.027, 1.121; p = 0.002) increased 30-day readmission risks and 1.067-fold (95% CI: 1.021, 1.115; p = 0.004) increased 180-day readmission risks in patients with neoplasm of the lower digestive tract. The MUNO and MUO phenotypes were independent risk factors of readmission in patients with liver or pancreatic neoplasm. Metabolic obesity status was independently associated with a high risk of severe and unplanned hospitalization within 30 days or 180 days. Conclusion: Both obesity and metabolic abnormalities are associated with a high risk for the poor prognosis of DSC patients. The effect of metabolic categories on the short- or long-term readmission of liver or pancreas cancers may be stronger than that of obesity.

Association between behavioral patterns and depression symptoms: dyadic interaction between couples.

Background: Behavioral patterns are sometimes associated with depression symptoms; however, few studies have considered the intra-couple effects. This study examined the effect of a spouses' behavioral patterns on depression symptoms within themself and in their spouse. Methods: A total of 61,118 childbearing age participants (30,559 husband-wife dyads) were surveyed. The depression symptoms were assessed using the nine-item Patient Health Questionnaire (PHQ-9). The behavioral patterns were identified by the latent class analysis. The effects of behavioral patterns on the couple's own depression symptoms (actor effect) and their partner's depression symptoms (partner effect) were analyzed using the Actor-Partner Interdependence Model (APIM). Results: Three behavioral patterns were identified: low-risk group, moderate-risk group, and high-risk group. The high risk of these behavior patterns would be associated with a higher score on the PHQ-9; for both husbands and wives, their behavioral patterns were positively associated with PHQ-9 scores (ßhusband = 0.53, P < 0.01; ßwife = 0.58, P < 0.01). Wives' behavioral patterns were also positively associated with their husbands' PHQ-9 scores (ß = 0.14, P < 0.01), but husbands' behavioral patterns were not associated with their wives' PHQ-9 scores. Conclusions: Wives' depression symptoms were affected only by their own behavioral patterns, whereas husbands' depression symptoms were influenced by both their own and their spouses' behavioral patterns.

Preconception exposure to environmental antibiotics among childbearing couples in Anhui and health risk assessment: A multicenter population-based representative study.

Only few studies have assessed the health effects due to preconception exposure to antibiotics among childbearing couples. This study investigated the status of preconception exposure to antibiotics among childbearing couples in Anhui, associated with health risks, and influencing factors. Overall, 1500 childbearing couples were randomly selected from the Reproductive Health of Childbearing Couples - Anhui Cohort (RHCC-AC). The urinary levels of 40 antibiotics and 2 metabolites were determined, and specific gravity (SG) adjusted concentrations of antibiotics were measured to assess health risks. Generalized linear models were used to assess the associations of urinary SG-adjusted concentration of antibiotics with demographic parameters and diet frequency. The total detection rates of all antibiotics were 98.9 % and 99.3 % in wives and husbands, respectively. The detection rates of veterinary antibiotics (VAs) and preferred as VAs (PVAs) were above 90 %. Among eight antibiotics, sulfonamides (95.1 %) and fluoroquinolones (87.6 %) had the highest detection rates in couples. Approximately four-fifths of couples were simultaneously exposed to at least three different antibiotics, and more than half of them were exposed to low concentrations of antibiotics. 8.9 % and 9.2 % of wives and husbands had hazard index value of antibiotics exposure greater than 1. Antibiotic concentrations were associated with residence, sampling season, and diet frequency. In Anhui, nearly 98 % of childbearing couples have environmental exposure to antibiotics, and VAs and PVAs are the primary antibiotics. More than 8 % of couples had health risks due to antibiotic exposure. Several potential determinants of urinary antibiotics deserve more attention in future research.

Dominant-negative HNF1α mutant promotes liver steatosis and inflammation by regulating hepatic complement factor D.

Patients with HNF1A variants may develop liver steatosis, while the underlying mechanism is still unclear. Here, we established a mouse model carrying the dominant-negative HNF1α P291fsinsC mutation (hHNF1Amut/-) and found that the mutant mice developed liver steatosis spontaneously under the normal chow diet. Transcriptome analysis showed significant upregulation of Cfd and other genes related to innate immune response in the liver of hHNF1Amut/- mice. The changes in lipid metabolism and complement pathways were also confirmed by proteomics. We demonstrated that HNF1α inhibited CFD expression in hepatocytes, and the P291fsinsC mutant could reverse this inhibitory effect. Furthermore, the suppression of CFD with specific inhibitor or siRNAs reduced triglyceride levels in hepatocytes, suggesting that CFD regulated hepatocyte lipid deposition. Our results demonstrate that the HNF1α P291fsinsC mutant promotes hepatic steatosis and inflammation by upregulating CFD expression, and targeting CFD may delay the progression of nonalcoholic fatty liver disease.

Closed thoracic drainage in elderly patients with chronic obstructive pulmonary disease complicated with spontaneous pneumothorax: A retrospective study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) combined with spontaneous pneumothorax, is characterized by significant decline in lung function, and even cause cardiopulmonary failure and hypoxia. AIM: To evaluate the clinical effectiveness of central venous catheters and indwelling pleural catheters (IPC) in managing closed thoracic drainage in patients diagnosed with COPD with concomitant by spontaneous pneumothorax. METHODS: Retrospective analysis was conducted on the clinical information of 60 elderly patients with COPD complicated by spontaneous pneumothorax admitted to the Shexian Branch of the second affiliated hospital of Zhejiang university school of medicine between March 2020 and March 2023. The clinical efficacy, complications, hospitalization duration, and costs were compared between patients with an indwelling thoracic catheter and those with a central venous catheter. Univariate logistic regression was used to analyze the causes of catheter displacement. RESULTS: According to our findings, there were significant differences in the IPC group's clinical efficacy, catheter operation time, and lung recruitment time (P < 0.05). Comparing the complications after catheter treatment between the two groups revealed statistically significant variations in the incidence of postoperative analgesics, catheter abscission, catheter blockage, and subcutaneous emphysema in the IPC group (P < 0.05). Univariate analysis demonstrated significant differences between patients with and without catheter dislodgement regarding duty nurse's working years (less than three), Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (less than 15), lack of catheter suture fixation, and the proportion of catheters not fixed twice (P < 0.05). CONCLUSION: Our results demonstrated that when treating elderly COPD patients with spontaneous pneumothorax, indwelling thoracic catheters are more effective than the central venous catheter group. Patients' catheter shedding is influenced by the primary nurse's working years, APACHE II scores, and catheter fixation technique.

Upregulation of WDR6 drives hepatic de novo lipogenesis in insulin resistance in mice.

Under normal conditions, insulin promotes hepatic de novo lipogenesis (DNL). However, during insulin resistance (IR), when insulin signalling is blunted and accompanied by hyperinsulinaemia, the promotion of hepatic DNL continues unabated and hepatic steatosis increases. Here, we show that WD40 repeat-containing protein 6 (WDR6) promotes hepatic DNL during IR. Mechanistically, WDR6 interacts with the beta-type catalytic subunit of serine/threonine-protein phosphatase 1 (PPP1CB) to facilitate PPP1CB dephosphorylation at Thr316, which subsequently enhances fatty acid synthases transcription through DNA-dependent protein kinase and upstream stimulatory factor 1. Using molecular dynamics simulation analysis, we find a small natural compound, XLIX, that inhibits the interaction of WDR6 with PPP1CB, thus reducing DNL in IR states. Together, these results reveal WDR6 as a promising target for the treatment of hepatic steatosis.

Mediating effects of DNA methylation in the association between sleep quality and infertility among women of childbearing age.

BACKGROUND: This study aims to investigate the association between sleep quality and infertility among women and to explore the mediating effects of DNA methylation in this association. METHODS: This study is a population-based case-control study. The relationship between sleep quality and infertility was investigated in women with anovulatory infertility (n = 43) and healthy controls (n = 43). Genome-wide DNA methylation was profiled from peripheral blood samples using the Illumina Infinium Human Methylation 850k BeadChip. Differentially methylated CpGs between cases and controls were identified using the ChAMP R package. The mediating effect of DNA methylation between sleep quality and infertility among women was investigated using the Bayesian estimation method provided by the R package "mediation". RESULTS: The survey included 86 women of reproductive age, with 43 participants each in the case and control groups. The average age of the women was 27.6 ± 2.8 years (case group: 27.8 ± 3.0 years, control group: 27.4 ± 2.7 years). A total of 262 differentially methylated CpGs corresponding to 185 genes were identified. Difficulty falling asleep was a risk factor for infertility in women (OR = 3.69, 95%CI = 1.14, 11.99), and a causal mediation effect of DNA methylation CpGs was found. The mediating effect coefficient for cg08298632 was 0.10 (95%CI = 0.01-0.22), and the proportion of the total effect mediated by this methylation site increased to 64.3%. CONCLUSION: These results suggest that DNA methylation CpGs (cg08298632) play a significant role in the relationship between difficulty falling asleep and infertility in females. These findings contribute to our understanding of the underlying mechanisms that connect difficulty falling asleep and infertility in women. Further studies are necessary to fully understand the biological significance and potential therapeutic applications of these findings. The identified DNA methylation sites provide new and valuable insights and potential targets for future studies aiming to prevent and treat female infertility.

Associating phthalate exposure during pregnancy with preschooler's FMI, ABSI and BRI trajectories via putative mechanism pathways.

Phthalates are well-known obesogens, but a few studies have explored their impacts on the childhood fat mass index (FMI), body shape index (ABSI) and body roundness index (BRI). Information from 2950 participants recruited in the Ma'anshan Birth Cohort was analyzed. The relationships between six maternal phthalate metabolites and their mixture and childhood FMI, ABSI and BRI were investigated. FMI, ABSI and BRI in children aged 3.5 y, 4.0 y, 4.5 y, 5.0 y, 5.5 y and 6.0 y were calculated. The latent class trajectory modeling categorized the FMI trajectories into "rapidly increasing FMI" (4.71%) and "stable FMI" (95.29%) groups; ABSI trajectories were categorized as "decreasing ABSI" (32.74%), "stable ABSI" (46.55%), "slowly increasing ABSI" (13.26%), "moderately increasing ABSI" (5.27%) and "rapidly increasing ABSI" (2.18%) groups; BRI trajectories were categorized as "increasing BRI" (2.82%), "stable BRI" (19.85%), and "decreasing BRI" (77.34%) groups. Prenatal MEP exposure was associated with repeated measurements of FMI (ß = 0.111, 95% CI = 0.002-0.221), ABSI (ß = 0.145, 95% CI = 0.023-0.268) and BRI (ß = 0.046, 95% CI = -0.005-0.097). Compared with each stable trajectory group, prenatal MEP (OR = 0.650, 95% CI = 0.502-0.844) and MBP (OR = 0.717, 95% CI = 0.984-1.015) were linked to a decreased risk of "decreasing BRI" in children; there was a negative relationship between MBP and the "decreasing ABSI" group (OR = 0.667, 95% CI = 0.487-0.914), and MEP increased the risks of "slowly increasing ABSI" (OR = 1.668, 95% CI = 1.210-2.299) and "rapidly increasing ABSI" (OR = 2.522, 95% CI = 1.266-5.024) in children. Phthalate mixture during pregnancy showed significant relationships with all anthropometric indicator trajectories, with MEP and MBP always being of the largest importance. In conclusion, this study suggested that prenatal phthalate coexposure increased the childhood probability of being in higher ABSI and BRI trajectory groups. That is, children were more likely to be obese when they were exposed to higher levels of some phthalate metabolites and their mixture. The low-molecular weight phthalates, including MEP and MBP, contributed the greatest weights.

The association between pregnancy-related anxiety and behavioral development in 18-month-old children: The mediating effects of parenting styles and breastfeeding methods.

BACKGROUND: Pregnancy-related anxiety (PRA) is a distinct type of anxiety from general anxiety, affects many pregnant women, and is correlated with poor behavioral development in children. However, the mediation paths were unclear. METHODS: A total of 2032 mother-infant pairs from the Ma'anshan Birth Cohort were included in the current study. Maternal PRA was assessed in the second and third trimesters. Children's behavioral development was evaluated at the age of 18 months. In addition, information on parenting styles and breastfeeding methods was obtained at postpartum. Multivariate regression and structural equation modeling were used to examine the associations between maternal PRA and children's behavioral development. RESULTS: Significant intercorrelations were found between maternal PRA, the potential mediators (parenting styles and breastfeeding methods), and 18-month-old children's ASQ scores. Parenting styles played an intermediary role in the relationship between maternal PRA and children's behavioral development (ß = 0.030, 95 % confidence interval: 0.017-0.051), and the mediating effect accounted for 29.1 % of the total effect. However, breastfeeding methods did not mediate the link between PRA and children's behavior. LIMITATIONS: Depression and postpartum anxiety were not controlled for in our analysis, which left us unable to estimate the independent impact of PRA on children's behavior. CONCLUSIONS: Parenting rather than breastfeeding is the mediating factor of behavioral problems in children caused by PRA.

Radiation prevents tumor progression by inhibiting the miR­93­5p/EphA4/NF­κB pathway in triple­negative breast cancer.

Breast cancer (BC) is the most common type of cancer in women. Triple­negative BC (TNBC) constitutes 10­15% of all BC cases and is associated with a poor prognosis. It has previously been reported that microRNA (miR)­93­5p is dysregulated in plasma exosomes from patients with BC and that miR­93­5p improves radiosensitivity in BC cells. The present study identified EphA4 as a potential target gene of miR­93­5p and investigated the pathway related to miR­93­5p in TNBC. Cell transfection and nude mouse experiments were performed to verify the role of the miR­93­5p/EphA4/NF­κB pathway. Moreover, miR­93­5p, EphA4 and NF­κB were detected in clinical patients. The results revealed that EphA4 and NF­κB were downregulated in the miR­93­5p overexpression group. By contrast, EphA4 and NF­κB expression levels were not significantly altered in the miR­93­5p overexpression + radiation group compared with those in the radiation group. Furthermore, overexpression of miR­93­5p with concomitant radiation therapy significantly decreased the growth of TNBC tumors in vivo. In conclusion, the present study revealed that miR­93­5p targeted EphA4 in TNBC through the NF­κB pathway. However, radiation therapy prevented tumor progression by inhibiting the miR­93­5p/EphA4/NF­κB pathway. Therefore, it would be interesting to elucidate the role of miR­93­5p in clinical research.

SP1 transcriptionally regulates UBE2N expression to promote lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) is the main cause of cancer-related death worldwide. Understanding the mechanisms of LUAD progression may provide insights into targeted therapy approaches for this malignancy. Ubiquitin-conjugating enzyme 2 N (UBE2N) has been demonstrated to play key roles in the progression of various cancers. However, the functions and mechanisms underlying UBE2N expression in LUAD are still unclear. In this study, we found that UBE2N is highly expressed in LUAD and patients with high UBE2N expression in their tumors have poor clinical outcomes. Moreover, we showed that UBE2N interference significantly inhibited LUAD progression in vitro and in vivo. At the molecular level, we demonstrated that the UBE2N is a bona fide target of transcription factor SP1. SP1 directly bound to the promoter of UBE2N and upregulated its expression in LUAD cells, which in turn contributed to the progression of LUAD. Furthermore, we found that there is a strong positive correlation between the expression of SP1 and UBE2N in LUAD samples. Importantly, LUAD patients with concomitantly high expression of SP1 and UBE2N were significantly associated with poor clinical outcomes. In conclusion, our study demonstrated that the SP1-UBE2N signaling axis might play a key role in the malignant progression of LUAD, which provides new targets and strategies for the treatment of LUAD.

Atypical pituitary hormone-target tissue axis.

A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an "atypical pituitary hormone-target tissue axis." This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the "atypical pituitary hormone-target tissue axis" could enable the identification of novel therapeutic targets for metabolic diseases.

Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study.

BACKGROUND: Based on self-report questionnaires, two previous epidemiological studies investigated the association between the exposure of women to antibiotics and their fertility. However, biomonitoring studies on low-dose antibiotic exposure, mainly from food and water, and its relation to the risk of infertility are missing. METHODS: Based on a case-control study design, 302 women with infertility (144 primary infertility, 158 secondary infertility) and 302 women with normal fertility, all aged 20-49 years, were recruited from Anhui Province, China, in 2020 and 2021. A total of 41 common antibiotics and two antibiotic metabolites in urine samples were determined by liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS/MS). RESULTS: Twenty-eight antibiotics with detection rates from 10% to 100% in both cases (median concentration: ∼2.294 ng/mL) and controls (∼1.596 ng/mL) were included in the analysis. Logistic regression analysis revealed that after controlling for confounding factors, high concentrations of eight individual antibiotics (sulfamethoxazole, sulfaclozine, sulfamonomethoxine, penicillin G, chlorotetracycline, ofloxacin, norfloxacin, and cyadox) and four antibiotic classes (sulfonamides, tetracyclines, quinoxalines, and veterinary antibiotics) were related to a high risk of female infertility, with odds ratios (ORs) ranging from 1.30 to 2.86, except for chlorotetracycline (OR = 6.34), while another nine individual antibiotics (sulfamethazine, azithromycin, cefaclor, amoxicillin, oxytetracycline, pefloxacin, sarafloxacin, enrofloxacin, and florfenicol) and classes of chloramphenicol analogs and human antibiotics were related to a reduced risk of infertility, with ORs ranging from 0.70 to 0.20. Based on restricted cubic spline models after controlling for confounding factors, we observed that the relationship between all of the above protective antibiotics and infertility was nonlinear: A certain concentration could reduce the risk of female infertility while exceeding a safe dose could increase the risk of infertility. CONCLUSION: These results provide preliminary evidence that the effects of antibiotics on female fertility vary based on the active ingredient and usage and imply the importance of exposure dose. Future studies are needed to verify these results by controlling for multiple confounding factors.

Synthesis of Paclitaxel Derivatives for Remote Loading into Liposomes and Improved Therapeutic Effect.

A series of novel paclitaxel derivatives modified by boronic acid according to the characteristics of the interaction between RB(OH)2 and different strapping agents of intraliposomal aqueous phase were designed and synthesized, which were then used to develop remote poorly water-soluble drugs loading into liposomes. Meanwhile, we screened nineteen paclitaxel boronic acid derivatives for their cytotoxic activities against three cancer cell lines (A549, HCT-116 and 4T1) and one normal cell line (LO2), and performed liposome formulation screening of active compounds. Among all the compounds, the liposome of 4d, with excellent drug-encapsulated efficiency (>95% for drug-to-lipid ratio of 0.1 w/w), was the most stable. Furthermore, the liposomes of compound 4d (8 mg/kg, 4 times) and higher dose of compound 4d (24 mg/kg, 4 times) showed better therapeutic effect than paclitaxel (8 mg/kg, 4 times) in the 4T1 tumor model in vivo, and the rates of tumor inhibition were 74.3%, 81.9% and 58.5%, respectively. This study provided a reasonable design strategy for the insoluble drugs to improve their drug loading into liposomes and anti-tumor effect in vivo.