Rate of transcription elongation and sequence-specific pausing by RNA polymerase I directly influence rRNA processing.

One of the first steps in ribosome biogenesis is transcription of the ribosomal DNA by RNA polymerase I (Pol I). Processing of the resultant rRNA begins cotranscriptionally, and perturbation of Pol I transcription elongation results in defective rRNA processing. Mechanistic insight regarding the link between transcription elongation and ribosome assembly is lacking because of limited in vivo methods to assay Pol I transcription. Here, we use native elongating transcript sequencing (NET-Seq) with a strain of Saccharomyces cerevisiae containing a point mutation in Pol I, rpa190-F1205H, which results in impaired rRNA processing and ribosome assembly. We previously demonstrated that this mutation caused a mild reduction in the transcription elongation rate of Pol I in vitro; however, transcription elongation by the mutant has not been characterized in vivo. Here, our findings demonstrate that the mutant Pol I has an increased pause propensity during processive transcription elongation both in vitro and in vivo. NET-Seq reveals that rpa190-F1205H Pol I displays alternative pause site preferences in vivo. Specifically, the mutant is sensitized to A/G residues in the RNA:DNA hybrid and at the last incorporated nucleotide position. Furthermore, both NET-Seq and EM analysis of Miller chromatin spreads reveal pileups of rpa190-F1205H Pol I throughout the ribosomal DNA, particularly at the 5' end of the 35S gene. This combination of in vitro and in vivo analyses of a Pol I mutant provides novel insights into Pol I elongation properties and indicates how these properties are crucial for efficient cotranscriptional rRNA processing and ribosome assembly.

The critical roles of m6A RNA methylation in lung cancer: from mechanism to prognosis and therapy.

Lung cancer, a highly malignant disease, greatly affects patients' quality of life. N6-methyladenosine (m6A) is one of the most common posttranscriptional modifications of various RNAs, including mRNAs and ncRNAs. Emerging studies have demonstrated that m6A participates in normal physiological processes and that its dysregulation is involved in many diseases, especially pulmonary tumorigenesis and progression. Among these, regulators including m6A writers, readers and erasers mediate m6A modification of lung cancer-related molecular RNAs to regulate their expression. Furthermore, the imbalance of this regulatory effect adversely affects signalling pathways related to lung cancer cell proliferation, invasion, metastasis and other biological behaviours. Based on the close association between m6A and lung cancer, various prognostic risk models have been established and novel drugs have been developed. Overall, this review comprehensively elaborates the mechanism of m6A regulation in the development of lung cancer, suggesting its potential for clinical application in the therapy and prognostic assessment of lung cancer.

Interleukin-4 activates the PI3K/AKT signaling to promote apoptosis and inhibit the proliferation of granulosa cells.

The inflammatory microenvironment has been demonstrated to play a role in folliculogenesis, ovulation and premature ovarian failure (POF), as well as infertility. In this study, we aimed to explore the role of inflammation in modulating growth and apoptosis in granulosa cells (GCs), the main components of ovarian follicles. ELISA was used to analyze the levels of inflammatory factors (IL-1ß, IL-4, IL-6 and IL-10) in follicular fluid samples and GCs derived from POF patients and healthy normal individuals. CCK-8, flow cytometry and TUNEL assays were used to assess the effect of IL-4 on GC growth and apoptosis. Western blotting was used to examine the effect of IL-4 on the activation of PI3K/Akt, Erk1/2 and Jnk signaling. The results showed that IL-4, IL-1ß and IL-6 levels were increased in follicular fluid samples and GCs derived from POF patients compared with those from healthy individuals. GC growth was weakened when cells were treated with IL-4, while apoptosis was increased. In addition, IL-4 increased the level of p-Akt/Akt in GCs. In addition, LY294002, an inhibitor of PI3K, abolished the effect of IL-4 by inhibiting GC growth and promoting apoptosis. In summary, this study demonstrated that IL-4 levels were increased in POF samples and that IL-4 could inhibit GC growth and induce GC apoptosis by activating PI3K/Akt signaling.

A review of cardiovascular effects and underlying mechanisms of legacy and emerging per- and polyfluoroalkyl substances (PFAS).

Cardiovascular disease (CVD) poses the leading threats to human health and life, and their occurrence and severity are associated with exposure to environmental pollutants. Per- and polyfluoroalkyl substances (PFAS), a group of widely used industrial chemicals, are characterized by persistence, long-distance migration, bioaccumulation, and toxicity. Some PFAS, particularly perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexanesulfonic acid (PFHxS), have been banned, leaving only legacy exposure to the environment and human body, while a number of novel PFAS alternatives have emerged and raised concerns, such as polyfluoroalkyl ether sulfonic and carboxylic acid (PFESA and PFECA) and sodium p-perfluorous nonenoxybenzene sulfonate (OBS). Overall, this review systematically elucidated the adverse cardiovascular (CV) effects of legacy and emerging PFAS, emphasized the dose/concentration-dependent, time-dependent, carbon chain length-dependent, sex-specific, and coexposure effects, and discussed the underlying mechanisms and possible prevention and treatment. Extensive epidemiological and laboratory evidence suggests that accumulated serum levels of legacy PFAS possibly contribute to an increased risk of CVD and its subclinical course, such as cardiac toxicity, vascular disorder, hypertension, and dyslipidemia. The underlying biological mechanisms may include oxidative stress, signaling pathway disturbance, lipid metabolism disturbance, and so on. Various emerging alternatives to PFAS also play increasingly prominent toxic roles in CV outcomes that are milder, similar to, or more severe than legacy PFAS. Future research is recommended to conduct more in-depth CV toxicity assessments of legacy and emerging PFAS and explore more effective surveillance, prevention, and treatment strategies, accordingly.

Unique regulatory roles of ncRNAs changed by PM2.5 in human diseases.

PM2.5 is a type of particulate matter with an aerodynamic diameter smaller than 2.5 µm, and exposure to PM2.5 can adversely damage human health. PM2.5 may impair health through oxidative stress, inflammatory reactions, immune function alterations and chromosome or DNA damage. Through increasing in-depth studies, researchers have found that noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs), circular RNAs (circRNAs) as well as long noncoding RNAs (lncRNAs), might play significant roles in PM2.5-related human diseases via some of the abovementioned mechanisms. Therefore, in this review, we mainly discuss the regulatory function of ncRNAs altered by PM2.5 in human diseases and summarize the potential molecular mechanisms. The findings reveal that these ncRNAs might induce or promote diseases via inflammation, the oxidative stress response, cell autophagy, apoptosis, cell junction damage, altered cell proliferation, malignant cell transformation, disruption of synaptic function and abnormalities in the differentiation and status of immune cells. Moreover, according to a bioinformatics analysis, the altered expression of potential genes caused by these ncRNAs might be related to the development of some human diseases. Furthermore, some ncRNAs, including lncRNAs, miRNAs and circRNAs, or processes in which they are involved may be used as biomarkers for relevant diseases and potential targets to prevent these diseases. Additionally, we performed a meta-analysis to identify more promising diagnostic ncRNAs as biomarkers for related diseases.

Interaction of air pollution and meteorological factors on IVF outcomes: A multicenter study in China.

BACKGROUND: Previous studies revealed associations between air-pollutant exposure and in vitro fertilization (IVF) outcomes. However, modification effects of air pollution on IVF outcomes by meteorological conditions remain elusive. METHODS: This multicenter retrospective cohort study included 15,217 women from five northern Chinese cities during 2015-2020. Daily average concentrations of air pollutants (PM2.5, PM10, O3, NO2, SO2, and CO) and meteorological factors (temperature, relative humidity, wind speed, and sunshine duration) during different exposure windows were calculated as individual approximate exposure. Generalized estimating equations models and stratified analyses were conducted to assess the associations of air pollution and meteorological conditions with IVF outcomes and estimate potential interactions. RESULTS: Positive associations of wind speed and sunshine duration with pregnancy outcomes were detected. In addition, we observed that embryo transfer in spring and summer had a higher likelihood to achieve a live birth compared with winter. Exposure to PM2.5, SO2, and O3 was adversely correlated with pregnancy outcomes in fresh IVF cycles, and the associations were modified by air temperature, relative humidity, and wind speed. The inverse associations of PM2.5 and SO2 exposure with biochemical pregnancy were stronger at lower temperatures and humidity. Negative associations of PM2.5 with clinical pregnancy were only significant at lower temperatures and wind speeds. Moreover, the effects of O3 on live birth were enhanced by higher wind speed. CONCLUSIONS: Our results suggested that the associations between air-pollutant exposure and IVF outcomes were modified by meteorological conditions, especially temperature and wind speed. Women undergoing IVF treatment should be advised to reduce outdoor time when the air quality was poor, particularly at lower temperatures.

Integrative analysis of DNA methylome and transcriptome reveals epigenetic regulation of bisphenols-induced cardiomyocyte hypertrophy.

Cardiac hypertrophy, a kind of cardiomyopathic abnormality, might trigger heart contractile and diastolic dysfunction, and even heart failure. Currently, bisphenols (BPs) including bisphenol A (BPA), and its alternatives bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol S (BPS) are ubiquitously applied in various products and potentially possess high cardiovascular risks for humans. However, the substantial experimental evidences of BPs on heart function, and their structure-related effects on cardiomyocyte hypertrophy are still urgently needed. DNA methylation, a typical epigenetics, play key roles in BPs-induced transcription dysregulation, thereby affecting human health including cardiovascular system. Thus, in this study, we performed RNA-seq and reduced representation bisulfite sequencing (RRBS) to profile the landscapes of BPs-induced cardiotoxicity and to determine the key roles of DNA methylation in the transcription. Further, the capabilities of three BPA analogues, together with BPA, in impacting heart function and changing DNA methylation and transcription were compared. We concluded that similar to BPA, BPAF, BPF and BPS exposure deteriorated heart function in a mouse model, and induced cardiomyocyte hypertrophy in a H9c2 cell line. BPAF, BPF and BPS all played BPA-like roles in both transcriptive and methylated hierarchies. Moreover, we validated the expression levels of four cardiomyocyte hypertrophy related candidate genes, Psmc1, Piptnm2, Maz and Dusp18, which were all upregulated and with DNA hypomethylation. The findings on the induction of BPA analogues on cardiomyocyte hypertrophy and DNA methylation revealed their potential detrimental risks in heart function of humans.

A review of the occurrence, metabolites and health risks of butylated hydroxyanisole (BHA).

Butylated hydroxyanisole (BHA) is mainly used as a food additive due to its antioxidant properties, which prevent or delay oxidation reactions and extend the storage life of products. The widespread use of BHA has led to its extensive presence in various environmental matrices and human tissues. Food intake is the main route of human exposure to BHA. Under different conditions, BHA can produce different metabolites, with tert-butyl hydroquinone (TBHQ) being one of the major products. Several studies have shown that BHA could cause thyroid system damage, metabolic and growth disorders, neurotoxicity, and carcinogenesis. Mechanisms such as endocrine disruption, genotoxicity, disturbances of energy metabolism, reactive oxygen species (ROS) production, signaling pathways, and imbalances in calcium homeostasis appear to be associated with the toxic effects of BHA. Avoiding the toxic effects of BHA to the maximum extent possible is a top priority. Finding safe, non-toxic and environmentally friendly alternatives to BHA should be the focus of subsequent research. In all, this review summarized the current situation related to BHA and might make recommendations for future research directions. © 2023 Society of Chemical Industry.

Enrichment, bioaccumulation and human health assessment of organochlorine pesticides in sediments and edible fish of a plateau lake.

The organochlorine pesticides (OCPs) are with features of persistence, high toxicity, bioaccumulation and adverse impact on ecosystems and human beings. Although OCPs pollutions have been observed in the plateau lakes, comprehensive understandings in the distribution characteristics and human health risks of OCPs in these valuable but fragile ecosystems are limited. We here investigated the distribution, bioaccumulation process and health risks of OCPs in the Jianhu lake, a representative plateau lake in China. The endrin ketone, endrin aldehyde and heptachlor were the most dominant species in surface and columnar sediments. Their total contents ranged between 0 ~ 1.92 × 103 ng·g-1. The distribution of OCPs in sediment cores combined with chronology information indicated that the fast accumulation of OCPs happened during the last decades. Combining the distribution features of OCPs in different sources with mixing model results of carbon isotope (δ13C), farming area was identified as the main source (46%), and the OCPs were transported to lake by inflow-rivers (37%). The enrichment of OCPs in sediments caused considerable bioaccumulation of OCPs in local fish (∑OCPs 0-3199.93 ng·g-1, dw) with the bio-sediment accumulation factor (BSAF) ranging from ND to 9.41. Moreover, growing time was another key factor governing the accumulation in specific species (Carassius auratus and Cyprinus carpio). Eventually, the carcinogenic risk index (CRI) and exposure risk index (ERI) of the endrin category and aldrin exceeded the reference value, indicating relatively high health risks through consumption of fish. Overall, this study systematically illustrated the bioaccumulation process and health risks of OCPs in the typical plateau lake, providing theoretical support for the better protection of this kind of lakes.

Multiple Infection and Human Immunodeficiency Virus Superinfection Among Persons who Inject Drugs in Indonesia and Ukraine.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 074 study evaluated an integrated human immunodeficiency virus (HIV) treatment and prevention strategy among persons who inject drugs (PWID) in Indonesia, Ukraine, and Vietnam. We previously detected multiple HIV infection in 3 of 7 (43%) of seroconverters with 3-8 HIV strains per person. In this report, we analyzed multiple HIV infection and HIV superinfection (SI) in the HPTN 074 cohort. METHODS: We analyzed samples from 70 participants in Indonesia and Ukraine who had viral load >400 copies/mL at enrollment and the final study visit (median follow-up, 2.5 years). HIV was characterized with Sanger sequencing, next-generation sequencing, and phylogenetic analysis. Additional methods were used to characterize a rare case of triple-variant SI. RESULTS: At enrollment, multiple infection was detected in only 3 of 58 (5.2%) participants with env sequence data. SI was detected in only 1 of 70 participants over 172.3 person-years of follow-up (SI incidence, 0.58/100 person-years [95% confidence interval, .015-3.2]). The SI case involved acquisition of 3 HIV strains with rapid selection of a strain with a single pol region cluster. CONCLUSIONS: These data from a large cohort of PWID suggest that intrahost viral selection and other factors may lead to underestimation of the frequency of multiple HIV infection and SI events.

Previous caesarean delivery and the presence of caesarean scar defects could affect pregnancy outcomes after in vitro fertilization frozen-thawed embryo transfer: a retrospective cohort study.

BACKGROUND: Due to various iatrogenic and social factors, the global caesarean delivery (CD) rate has risen sharply in the past 30 years. It is more complicated and dangerous for women with a scarred uterus to experience pregnancy again than for women with a previous vaginal delivery (VD). In this study we investigated the impact of previous caesarean delivery (CD) and caesarean scar defects (CSDs) on pregnancy outcomes after in vitro fertilization frozen-thawed embryo transfer (IVF-FET). METHODS: We conducted a retrospective cohort study that included 1122 women aged < 40 years who had a history of only one parturition (after 28 weeks of pregnancy) and who underwent their first FET cycle between January 2014 and January 2020. Patients were divided into the CD group, VD group, and CSD group. Thereafter, according to the number of transferred embryos, the CD, VD, and CSD groups were divided into the single embryo transfer (SET) group and the double embryo transfer (DET) group. Outcome measures in this study were live birth, clinical pregnancy, multiple pregnancy, ectopic pregnancy, pregnancy loss, pregnancy complications, preterm birth, and neonatal birth weight. Multivariate logistic regression was performed to evaluate the relationship between pregnancy outcomes and CD. RESULTS: In SET patients, the clinical pregnancy and live birth rates were decreased in the CSD group compared with the VD and CD groups. In DET patients, the clinical pregnancy and live birth rates were significantly lower in theCSD group than in the CD and VD groups. After adjustment for confounders, previous CD and CSD were associated with a significantly lower clinical pregnancy rate and live birth rate than previous VD in the total sample. This effect was observed in DET patients, but not in SET patients. Additionally, DET patients with previous CD had a significantly higher multiple pregnancy rate (AOR = 0.47, 95% CI = 0.29, 0.75, P = 0.002) than those with previous VD, but no significant associations were observed in CSD and multiple pregnancies (AOR = 0.55, 95% CI = 0.23, 1.34, P = 0.192) between DET patients with CD and those with VD after adjusting for potential confounders. CONCLUSIONS: Our study showed that during an FET cycle, previous CD and the presence of a CSD could negatively affect pregnancy outcomes especially in DET patients.

Hysteroscopic resection of type 3 fibroids could improve the pregnancy outcomes in infertile women: a case-control study.

BACKGROUND: Type 3 fibroids are a special subtype of intramural fibroids that are likely to affect the pregnancy outcomes of assisted reproductive techniques. Hysteroscopic resection is a treatment for type 3 fibroids, but there has few study of its efficacy to date. In this study we evaluated the effect of hysteroscopic resection of type 3 fibroids on the pregnancy outcomes in infertile women. METHODS: This retrospective case-control study was conducted from January 1, 2014 to June 30, 2021. Patients who underwent IVF-ICSI in our unit were divided into a type 3 fibroid group and a hysteroscopic myomectomy group. The inclusion criteria for the type 3 fibroid group and the hysteroscopic myomectomy group were as follows: 1) age ≤ 40 years; 2) fibroid diameter or total fibroid diameter > 2.0 cm. The following exclusion criteria were used: 1) oocyte donor treatment cycles and 2) presence of chromosomal abnormalities; 3) history of other uterine surgery; 4) presence of intracavitary lesions, including submucosal fibroids; 5) single fibroid > 5.0 cm; 6) cervical fibroids; 7) unclear ultrasound description of fibroids; 8) preimplantation genetic testing was performed and 9) congenital or acquired uterine malformations. The control group in our study was selected from patients who were treated with IVF only because of fallopian tube factors. According to the age of the type 3 fibroid group and hysteroscopic myomectomy group, random sampling was carried out in the patients between 25 and 47 years of age to determine a control group. The outcomes measured included the average transfer times to live birth, cumulative clinical pregnancy rate, and cumulative live birth rate. RESULTS: A total of 302 cycles were enrolled in our study, including 125 cycles with type 3 fibroids, 122 cycles with hysteroscopic myomectomy, and 139 cycles of control patients. The average transfer times to live birth were significantly higher in the type 3 fibroid group than in the other two groups. The frequency of cumulative live births in the type 3 fibroid group was significantly lower than that in the control group. Compared with the control group, the hysteroscopic myomectomy patients had no statistically significant differences in the cumulative clinical pregnancy rate and cumulative live birth rate. CONCLUSIONS: Type 3 fibroids significantly reduced the cumulative live birth rate of IVF patients. Ultrasound-guided hysteroscopic myomectomy can be used as a treatment for type 3 fibroids and could improve the pregnancy outcomes in infertile women.

Heterotopic cervical pregnancy: Case report and literature review.

Cervical pregnancy (CP) is a rare form of ectopic pregnancy (EP) in which the embryo implants and grows inside the endocervical canal. Heterotopic cervical pregnancy is an even rare form of EP, in which at least two embryos are simultaneously implanted in different sites and only one in the uterine cavity. Although many treatment approaches are available, the ideal management remains unclear. Here, we describe two cases of CP caused by assisted reproductive technologies (ART). One case underwent fertilization with intracytoplasmic sperm injection (ICSI) for male factor infertility, and the other was frozen-thawed embryo transfer (FET) following conventional in vitro fertilization (IVF). Both cases were successfully treated with ultrasound-guided cervical pregnancy aspiration, and intrauterine pregnancies were effectively protected. To the best of our knowledge, these two were rare case reports use aspiration without additional methods and intrauterine pregnancy achieved live birth.

Insights into the regulatory role of Plexin D1 signalling in cardiovascular development and diseases.

Plexin D1 (PLXND1), which was previously thought to mediate semaphorin signalling, belongs to the Plexin family of transmembrane proteins. PLXND1 cooperates mostly with the coreceptor neuropilin and participates in many aspects of axonal guidance. PLXND1 can also act as both a tumour promoter and a tumour suppressor. Emerging evidence suggests that mutations in PLXND1 or Semaphorin 3E, the canonical ligand of PLXND1, can lead to serious cardiovascular diseases, such as congenital heart defects, CHARGE syndrome and systemic sclerosis. Upon ligand binding, PLXND1 can act as a GTPase-activating protein (GAP) and modulate integrin-mediated cell adhesion, cytoskeletal dynamics and cell migration. These effects may play regulatory roles in the development of the cardiovascular system and disease. The cardiovascular effects of PLXND1 signalling have gradually been elucidated. PLXND1 was recently shown to detect physical forces and translate them into intracellular biochemical signals in the context of atherosclerosis. Therefore, the role of PLXND1 in cardiovascular development and diseases is gaining research interest because of its potential as a biomarker and therapeutic target. In this review, we describe the cardiac effects, vascular effects and possible molecular mechanisms of PLXND1 signalling.

Human Immunodeficiency Virus (HIV) Drug Resistance, Phylogenetic Analysis, and Superinfection Among Men Who Have Sex with Men and Transgender Women in Sub-Saharan Africa: HIV Prevention Trials Network (HPTN) 075 Study.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 075 study evaluated the feasibility of enrolling and retaining men who have sex with men (MSM) and transgender women (TGW) from Kenya, Malawi, and South Africa. During the study follow-up, 21 participants acquired human immunodeficiency virus (HIV) (seroconverters). We analyzed HIV subtype diversity, drug resistance, transmission dynamics, and HIV superinfection data among MSM and TGW enrolled in HPTN 075. METHODS: HIV genotyping and drug resistance testing were performed for participants living with HIV who had viral loads >400 copies/mL at screening (prevalent cases, n = 124) and seroconverters (n = 21). HIV pol clusters were identified using Cluster Picker. Superinfection was assessed by a longitudinal analysis of env and pol sequences generated by next-generation sequencing. RESULTS: HIV genotyping was successful for 123/124 prevalent cases and all 21 seroconverters. The major HIV subtypes were A1 (Kenya) and C (Malawi and South Africa). Major drug resistance mutations were detected in samples from 21 (14.6%) of 144 participants; the most frequent mutations were K103N and M184V/I. Phylogenetic analyses identified 11 clusters (2-6 individuals). Clusters included seroconverters only (n = 1), prevalent cases and seroconverters (n = 4), and prevalent cases only (n = 6). Superinfections were identified in 1 prevalent case and 2 seroconverters. The annual incidence of superinfection was higher among seroconverters than among prevalent cases, and was higher than the rate of primary HIV infection in the cohort. CONCLUSIONS: This report provides important insights into HIV genetic diversity, drug resistance, and superinfection among MSM and TGW in sub-Saharan Africa. These findings may help to inform future HIV prevention interventions in these high-risk groups.

Evaluation of Phylogenetic Methods for Inferring the Direction of Human Immunodeficiency Virus (HIV) Transmission: HIV Prevention Trials Network (HPTN) 052.

BACKGROUND: Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. METHODS: Complete next-generation sequencing (NGS) data were obtained for 105 unique index-partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env). RESULTS: Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction. CONCLUSIONS: We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data.

Caesarean section defects may affect pregnancy outcomes after in vitro fertilization-embryo transfer: a retrospective study.

BACKGROUND: Caesarean section rates are rising worldwide. One adverse effect of caesarean section reported in some studies is an increased risk of subfertility. Only a few studies have assessed the relationship between the previous mode of delivery and in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) reproductive outcomes. In this study, we primarily investigated the impact of a history of caesarean section with or without defects on IVF/ICSI-ET outcomes compared to a vaginal delivery history. METHODS: This retrospective study included 834 women who had a IVF or ICSI treatment at our centre between 2015 and 2019 with a delivery history. In total, 401 women with a previous vaginal delivery (VD) were assigned to the VD group, and 433 women with a history of delivery by caesarean section were included, among whom 359 had a caesarean scar (CS) without a defect and were assigned to the CS group and 74 had a caesarean section defect (CSD) and were assigned to the CSD group. Baseline characteristics of the three groups were compared and analysed. Binary logistic regression analyses were performed to explore the association between clinical outcomes and different delivery modes. RESULTS: There were no significant differences in the live birth rate, biochemical pregnancy rate, clinical pregnancy rate, mean implantation rate or abnormal pregnancy rate between the CS and VD groups However, the live birth rate and mean implantation rate in the CSD group were significantly lower than those in the VD group (21.6 vs 36.4%, adjusted OR 0.50 [0.27-0.9]; 0.25 ± 0.39 vs 0.35 ± 0.41, adjusted OR 0.90 [0.81-0.99]). Among women aged ≤ 35 years, the subgroup analyses showed that the live birth rate, biochemical pregnancy rate, clinical pregnancy rate, and mean implantation rate in the CSD group were all significantly lower than those in the VD group (21.4 vs 45.8%, adjusted OR 0.35[0.15 ~ 0.85]; 38.1 vs 59.8%, adjusted OR 0.52[0.24-0.82]; 31.0 vs 55.6%, adjusted OR 0.43[0.19-0.92]; 0.27 ± 0.43 vs 0.43 ± 0.43, adjusted OR 0.85[0.43 ± 0.43]). For women older than 35 years, there was no statistically significant difference in any pregnancy outcome among the three groups. CONCLUSIONS: This study suggested that the existence of a CS without a defect does not decrease the live birth rate after IVF or ICSI compared with a previous VD. However, the presence of a CSD in women, especially young women (age ≤ 35 years), significantly impaired the chances of subsequent pregnancy.

Pregnancy outcomes of infertile women with ultrasound-diagnosed adenomyosis for in vitro fertilization and frozen-thawed embryo transfer.

OBJECTIVE: This study aimed to investigate the effect of ultrasound-diagnosed adenomyosis on assisted pregnancy outcomes, i.e., in vitro fertilization-embryo transfer (IVF-ET). METHODS: This was a retrospective cohort study of 18,568 women who had received their first frozen-thawed ET cycle in Center of Reproductive Medicine, Children's Hospital of Shanxi and Women Health Center of Shanxi and the Reproductive Medicine Center of Tianjin Central Obstetrics and Gynecology Hospital from January 2014 to May 2019. A total of 5,087 patients met the inclusion and exclusion criteria, and they were divided into two groups: adenomyosis with tubal factor infertility (study group, n = 193) and only tubal factor infertility (control group, n = 4894). After a 1:1 propensity score match (caliper value = 0.005), 360 cases were matched in the end. RESULT: There was no statistical difference in the embryo implantation rate, clinical pregnancy rate, or multiple pregnancy rate between the two groups (28.4% vs. 31.7%, 42.2% vs. 42.8%, and 11.7% vs. 12.8%, respectively; P > 0.05). However, the early miscarriage rate in the adenomyosis group was significantly higher than that in the control group (13.3% vs. 5.6%, respectively; P = 0.012). The live birth rate was 22.8% in the women with adenomyosis and was observed to be significantly lower than 33.3% in the control group (P = 0.026). The patients with adenomyosis had a higher incidence of pregnancy complications than those without (4.4% vs. 0.6%, respectively; P = 0.018), but the neonatal birth weight was not related to adenomyosis. CONCLUSION: Women with adenomyosis should be treated as being at high risk of early miscarriage. However, maternal adenomyosis has no effect on the birth weight of the newborn.

Phylogenetic Analysis of Human Immunodeficiency Virus from People Who Inject Drugs in Indonesia, Ukraine, and Vietnam: HPTN 074.

BACKGROUND: HIV Prevention Trials Network (HPTN) 074 evaluated human immunodeficiency virus (HIV) prevention interventions for people who inject drugs (PWID) in Indonesia, Ukraine, and Vietnam. Study interventions included support for HIV infection and substance use treatment. The study enrolled index participants living with HIV and injection partners who were not living with HIV. Seven partners acquired HIV infection during the study (seroconverters). We analyzed the phylogenetic relatedness between HIV strains in the cohort and the multiplicity of infection in seroconverters. METHODS: Pol region consensus sequences were used for phylogenetic analysis. Data from next-generation sequencing (NGS, env region) were used to evaluate genetic linkage of HIV from the 7 seroconverters and the corresponding index participants (index-partner pairs), to analyze HIV from index participants in pol sequence clusters, and to analyze multiplicity of HIV infection. RESULTS: Phylogenetic analysis of pol sequences from 445 index participants and 7 seroconverters identified 18 sequence clusters (2 index-partner pairs, 1 partner-partner pair, and 15 index-only groups with 2-7 indexes/cluster). Analysis of NGS data confirmed linkage for the 2 index-partner pairs, the partner-partner pair, and 11 of the 15 index-index clusters. The remaining 5 seroconverters had infections that were not linked to the corresponding enrolled index participant. Three (42.9%) of the 7 seroconverters were infected with more than 1 HIV strain (3-8 strains per person). CONCLUSIONS: We identified complex patterns of HIV clustering and linkage among PWID in 3 communities. This should be considered when designing strategies for HIV prevention for PWID. CLINICAL TRIALS REGISTRATION: NCT02935296.

The functional roles of exosomal long non-coding RNAs in cancer.

Exosomes are extracellular membranous vesicles that are secreted by various cell types. Exosomes have become indispensable facilitators in the exchange of information between cells. More importantly, exosomes perform a crucial role in a variety of diseases including cancers. Long non-coding RNAs (lncRNAs) are over 200 nucleotides long transcripts that exhibit no or limited protein-coding potentials. LncRNAs are an emerging group of regulatory RNAs and can be selectively packaged into exosomes. Exosomal lncRNAs play a central role in carcinogenesis and cancer progression by modulating tumor growth, metastasis, angiogenesis and chemoresistance. Moreover, exosomal lncRNAs function as messengers in cell-to-cell communication, and thus remodel the tumor microenvironment. Their function relevance in cancer biology hints at the possibility of employing exosomal lncRNAs as promising, non-invasive biomarkers for further cancer therapy. In this review, we provide an overview of current research on the functional roles of exosomal lncRNAs in cancer and discuss their potential clinical applications as diagnostic biomarkers and therapeutic targets for cancers.