Deciphering the comprehensive knowledgebase landscape featuring infertility with IDDB Xtra.

Infertility affects ∼15% of couples globally and half of cases are related to genetic disorders. Despite growing data and unprecedented improvements in high-throughput sequencing technologies, accumulated fertility-related issues concerning genetic diagnosis and potential treatment are urgent to be solved. However, there is a lack of comprehensive platforms that characterise various infertility-related records to provide research applications for exploring infertility in-depth and genetic counselling of infertility couple. To solve this problem, we provide IDDB Xtra by further integrating phenotypic manifestations, genomic datasets, epigenetics, modulators in collaboration with numerous interactive tools into our previous infertility database, IDDB. IDDB Xtra houses manually-curated 2369 genes of human and nine model organisms, 273 chromosomal abnormalities, 884 phenotypes, 60 genomic datasets, 464 epigenetic records, 1144 modulators relevant to infertility diagnosis and treatment. Additionally, IDDB Xtra incorporated customized graphical applications for researchers and clinicians to decipher in-depth disease mechanisms from the perspectives of developmental atlas, mutation effects, and clinical manifestations. Users can browse genes across developmental stages of human and mouse, filter candidate genes, mine potential variants and retrieve infertility biomedical network in an intuitive web interface. In summary, IDDB Xtra not only captures valuable research and data, but also provides useful applications to facilitate the genetic counselling and drug discovery of infertility. IDDB Xtra is freely available at https://mdl.shsmu.edu.cn/IDDB/and http://www.allostery.net/IDDB.

The role of immune system in atherosclerosis: Molecular mechanisms, controversies, and future possibilities.

Numerous cardiovascular disorders have atherosclerosis as their pathological underpinning. Numerous studies have demonstrated that, with the aid of pattern recognition receptors, cytokines, and immunoglobulins, innate immunity, represented by monocytes/macrophages, and adaptive immunity, primarily T/B cells, play a critical role in controlling inflammation and abnormal lipid metabolism in atherosclerosis. Additionally, the finding of numerous complement components in atherosclerotic plaques suggests yet again how heavily the immune system controls atherosclerosis. Therefore, it is essential to have a thorough grasp of how the immune system contributes to atherosclerosis. The specific molecular mechanisms involved in the activation of immune cells and immune molecules in atherosclerosis, the controversy surrounding some immune cells in atherosclerosis, and the limitations of extrapolating from relevant animal models to humans were all carefully reviewed in this review from the three perspectives of innate immunity, adaptive immunity, and complement system. This could provide fresh possibilities for atherosclerosis research and treatment in the future.

Incorporating Naphthalene and Halogen into Near-Infrared Double-Cable Conjugated Polymers for Single-Component Organic Solar Cells with Low-Voltage Losses.

The invention of near-infrared pedant-based double-cable conjugated polymers has demonstrated remarkable efficacy in single-component organic solar cells (SCOSCs). This work focuses on the innovative double-cable conjugated polymers aimed at attaining good absorption and suitable energy levels. Specifically, in the aromatic side units, the electron-donating (D) part is designed using a thieno[3,4-c]pyrrole-4,6-dione (TPD) as a core unit, flanked by two cyclopentadithiophene groups on either side. The electron-deficient (A) terminal groups consist of 2-(3-oxo-2,3-dihydro-1H-cyclopenta[b]naphthalen-1-ylidene) malononitrile (NC), which can be further modified through fluorination to modulate the physical properties and packing modes of the acceptor material. The resulting double-cable conjugated polymers exhibit broad absorption spectra spanning 500-850 nm and possess lowered Frontier energy levels when incorporating fluorine elements, providing decreased voltage losses in SCOSCs. Therefore, SCOSCs fabricated using these polymers have demonstrated power conversion efficiencies ranging from 7.6 to 10.2%, in which fluorine-containing double-cable conjugated polymers showed higher PCEs due to more favorable crystalline packing, enhanced exciton dissociation probability, and charge-transporting ability.

Non-Covalent Interactions between Polyvinyl Chloride and Conjugated Polymers Enable Excellent Mechanical Properties and High Stability in Organic Solar Cells.

The incorporation of insulating polymers into conjugated polymers has been widely explored as a strategy to improve mechanical properties of flexible organic electronics. However, phase separation due to the immiscibility of these polymers has limited their effectiveness. In this study, we report the discovery of multiple non-covalent interactions that enhances the miscibility between insulating and conjugated polymers, resulting in improved mechanical properties. Specifically, we have added polyvinyl chloride (PVC) into the conjugated polymer PM6 and observed a significant increase in solution viscosity, indicative of favorable miscibility between these two polymers. This phenomenon has been rarely observed in other insulating/conjugated polymer composites. Thin films of PM6/PVC exhibit a much-improved crack-onset strain of 19.35 %, compared to 10.12 % for pristine PM6 films. Analysis reveal that a "cyclohexyl-like" structure formed through dipole-dipole interactions and hydrogen bonding between PVC and PM6 acted as a cross-linking site in the thin films, leading to improved mechanical properties. Moreover, PM6/PVC blend films have demonstrated excellent thermal and bending stability when applied as an electron donor in organic solar cells. These findings provide new insights into non-covalent interactions that can be utilized to enhance the properties of conjugated polymers and may have potential applications in flexible organic electronics.

Synthesis and demulsification mechanism of an ionic liquid with four hydrophobic branches and four ionic centers.

Stable emulsions can have numerous negative impacts on both the oil industry and the environment. This study focuses on the synthesis of two ionic liquids (via. PPBD and PPBH) with four hydrophobic branches and four ionic centers that can effectively treat oil-water emulsions at a low temperature of 40 °C. Their chemical structure was explored using Fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance hydrogen spectra (1H NMR). The effect of temperature, PPBD and PPBH concentration, oil-water ratio, salinity and pH value on the demulsification efficiency (DE) of W/O emulsion was studied detailly and several commercial demulsifiers were also used for comparison. Results revealed that by adding 250 mg/L of PPBH in an E30 emulsion and leaving it for 120 min at 40 °C, the DE could reach 96.34%. Meanwhile, in an E30 emulsion (oil-water mass ratio of 3:7) with 250 mg/L of PPBD, the DE of 95.23% could be obtained at 40 °C for 360 min. Especially, the DE of PPBH could reach 100% in an E70 emulsion (oil-water mass ratio of 7:3) at the same conditions. Additionally, the demulsifier (PPBH) exhibited excellent salt resistance and outperformed some commonly used commercial demulsifiers. Several methods were utilized to investigate the potential demulsification mechanism, including measuring interfacial tension (IFT), three-phase contact angle (CA), droplet contact time, zeta potential, and observing samples under optical microscopy.

Severity and Vaccine Effectiveness in Patients With the Omicron Variant of COVID-19 in Suzhou: A Retrospective Single-Center Study.

Background The Omicron variant of the coronavirus disease 2019 (COVID-19) virus has spread rapidly worldwide, even in areas with high vaccination rates. Consequently, it has further exacerbated the current global pandemic. In this study, we aimed to characterize the clinical severity of patients with the COVID-19 variant Omicron and analyze vaccine effectiveness in predicting clinical severity. Methodology A total of 142 patients who contracted the COVID-19 virus in the Omicron era were retrospectively studied, and differences in their clinical severity were analyzed. They were stratified as follows: unvaccinated vs. vaccinated, unvaccinated vs. one to two vaccine doses vs. three vaccine doses, and cycle threshold (CT) values ≤ 28 vs. CT > 28. Results Of the 142 patients, 27 were asymptomatic, 83 had mild disease, and 32 had moderate disease. The median age was 32 years for asymptomatic patients vs. 31 years for those with mild disease vs. 59 years for those with moderate disease (P＜0.05), and the direct medical hospitalization costs were ¥4901 for asymptomatic patients vs. ¥5259 for those with mild disease vs. ¥8378 for those with moderate disease (P＜0.05). Of the 142 patients, 112 (78.8%) were vaccinated, 11 (7.7%) had one vaccine dose, 63 (44.4%) had two vaccine doses, and 38 (26.7%) received three vaccine doses. The median direct medical cost in the vaccinated group was significantly lower than that in the unvaccinated group (¥5470.5 vs. ¥7535.5, P＜0.05). For ORF1ab and N genes, hospital stay length and direct medical cost significantly decreased in the group with CT values > 28 compared with those in the group with CT values ≤ 28 (P＜0.05). Multiple regression analysis showed that being ≥ 60 years old could be a predictor of moderate disease severity in patients, and three vaccine doses could be effective against moderate COVID-19. Conclusion Mild infection is the main clinical manifestation of the Omicron variant. Vaccination can significantly decrease direct Omicron-associated medical costs. Although vaccination cannot provide protection against severe disease caused by this variant, three vaccine doses are highly effective in preventing moderate COVID-19.

Histone mRNA polyadenylation-mediated inflammation underlies various virus infections and cancers.

The mechanistic understanding of virus infection and inflammation in many diseases is incomplete. Normally, messenger RNA (mRNA) tails of replication-dependent histones (RDH) that safeguard naked nuclear DNAs are protected by a specialized stem-loop instead of polyadenylation. Here, we showed that infection by various RNA viruses (including severe acute respiratory syndrome coronavirus 2) induced aberrant polyadenylation of RDH mRNAs (pARDH) that resulted in inflammation or cellular senescence, based on which we constructed a pARDH inflammation score (pARIS). We further investigated pARIS elevation in various disease conditions, including different types of virus infection, cancer, and cellular senescence. Notably, we found that pARIS was positively correlated with coronavirus disease 2019 severity in specific immune cell types. We also detected a subset of HIV-1 elite controllers characterized by pARDH "flipping" potentially mediated by HuR. Importantly, pARIS was positively associated with transcription of endogenous retrovirus but negatively associated with most immune cell infiltration in tumors of various cancer types. Finally, we identified and experimentally verified two pARIS regulators, ADAR1 and ZKSCAN1, which was first linked to inflammation. The ZKSCAN1 was known as a transcription factor but instead was shown to regulate pARIS as a novel RNA binding protein. Both regulators were upregulated under most infection and inflammation conditions. In conclusion, we unraveled a potential antiviral mechanism underlying various types of virus infections and cancers.

Ultrasensitive Optical Fiber Sensors Working at Dispersion Turning Point: Review.

Optical fiber sensors working at the dispersion turning point (DTP) have served as promising candidates for various sensing applications due to their ultrahigh sensitivity. In this review, recently developed ultrasensitive fiber sensors at the DTP, including fiber couplers, fiber gratings, and interferometers, are comprehensively analyzed. These three schemes are outlined in terms of operation principles, device structures, and sensing applications. We focus on sensitivity enhancement and optical transducers, we evaluate each sensing scheme based on the DTP principle, and we discuss relevant challenges, aiming to provide some clues for future research.

Study on Mechanical Failure Behavior of Steel-Wire Wound Reinforced Thermoplastic Pipe under Combined Internal Pressure and Soil Landslide Conditions.

A steel-wire wound reinforced thermoplastic pipe (SWW-RTP) has been widely utilized in many industrial areas, and a soil landslide is an inevitable hazardous extreme condition for the SWW-RTP as it is usually buried underground. It is imperative to study the mechanical failure behavior and the failure criterion of the SWW-RTP under the combination of internal pressure and soil landslide conditions, and this paper is the first study to investigate the topic. In this paper, groups of stress-strain curves of high-density polyethylene (HDPE) and steel wires were obtained by uniaxial tensile tests at different strain rates, with the help of a Digital Image Correlation device (DIC). A rate-dependent constitutive model was employed to represent the mechanical behavior of the HDPE and to help deduce the stress-strain curve of the HDPE under the required strain rate, estimated from the static simplification of the dynamic soil landslide. Afterwards, a finite element model of the SWW-RTP, embedded in a cubic of soil, was established with the software ABAQUS. The SWW-RTP model was composed of HDPE solid elements, embedded with steel-wire truss elements, and the soil was characterized with the extended Drucker-Prager model. A quartic polynomial displacement distribution was applied to the soil model to represent the soil landslide. Then, the mechanical response of the SWW-RTP was analyzed. It was found that the failure criterion of the HDPE yield was more suitable for the pipe subjected to internal pressure and soil landslide conditions, instead of the steel-wire strength failure criterion always used in traditional research on the SWW-RTP. Further, the influence of landslide width, internal pressure and steel-wire number were discussed. The larger the width of the landslide area, the gentler the deformation of the pipeline; this resulted in an increase in the maximum landslide and a decrease in the maximum curvature with the width of the landslide area. The relatively high internal pressure was beneficial to the safety of the SWW-RTP under landslide, because the internal pressure could increase the stiffness of the pipeline. The number of steel wires had a limited influence on the maximum landslide required for the SWW-RTP's failure. This work can be useful for the design and safe assessment of the SWW-RTP under internal pressure and soil landslide conditions.

Online quantitative substrate, product, and cell concentration in citric acid fermentation using near-infrared spectroscopy combined with chemometrics.

As a mature platform compound, citric acid (CA) is mainly produced by Aspergillus niger (A. niger) through submerged fermentation. However, the CA fermentation process is still regulated based on experience and limited offline data, so real-time monitoring and intelligent precise control of the fermentation process cannot be carried out. In this study, near-infrared (NIR) spectroscopy combined with different chemometrics methods was used to quantify the substrate, product, and cell concentration of CA fermentation online. The predictive performance of total sugar (TS), CA, and dry cell weight (DCW) concentrations were compared between traditional partial least squares (PLS) and intelligent stacked auto-encoder (SAE) modeling methods. Theresults showed that both PLS and SAE models had good performance in predicting TS and CA. The performance, accuracy, and precision of the PLS models are slightly better than those of the SAE models in predicting TS and CA. SAE model was superior to the PLS model in predicting DCW concentration. The SAE modeling method has advantages in predicting the concentration of complex components. In this study, the multi-parameter online prediction was realized in the complex system of CA fermentation, which provided the basis for real-time intelligent control of the fermentation process.

Neonatal outcomes and congenital malformations in children born after progestin-primed ovarian stimulation protocol.

Purpose: The purpose of this study is to assess the safety of progestin-primed ovarian stimulation (PPOS) protocol regarding the neonatal outcomes and congenital malformations in babies born after in vitro fertilization (IVF) and frozen embryo transfer (FET). Methods: In this large retrospective cohort study, a total of 16,493 infants born between 1 September 2013 and 31 July 2021 from IVF and FET cycles after treatment with either PPOS (n = 15,245) or gonadotropin-releasing hormone antagonist (GnRH-ant) (n = 1,248) were finally enrolled. The primary outcome measure was the incidence of congenital malformations. The secondary outcome measures were rates of low birth weight (LBW), very low birth weight (VLBW), preterm birth (PTB), very preterm birth (VPTB), and early neonatal death. Results: Birth characteristics for both singletons and twins regarding the sex of infants, gestational age, birth weight, and birth length were comparable between the PPOS group and the GnRH-ant group. Rates of LBW, VLBW, PTB, VPTB, and early neonatal death were also similar. The reanalysis using propensity score matching (PSM) and multivariable logistic regression indicated that the PPOS protocol could not increase the risk of adverse neonatal outcomes compared with the GnRH-ant protocol. Furthermore, no significant difference was observed in the overall incidence of congenital malformations in live-born babies. After PSM and controlling for all confounders, the results remained insignificant with an adjusted odds ratio of 0.66 [95% confidence interval (CI) 0.32-1.34] and 2.43 [95% CI 0.97-6.06], respectively, for singletons and twins. Conclusions: Our study suggests that compared with GnRH-ant treatment for IVF, the PPOS protocol could not produce a negative effect on the newborn population in terms of neonatal outcomes and congenital malformations.

U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3' end processing core factors.

In eukaryotic cells, both alternative splicing and alternative polyadenylation (APA) play essential roles in the gene regulation network. U1 small ribonucleoprotein particle (U1 snRNP) is a major component of spliceosome, and U1 snRNP complex can suppress proximal APA sites through crosstalking with 3' end processing factors. However, here we show that both knockdown and overexpression of SNRPA, SNRPC, SNRNP70, and SNRPD2, the U1 snRNP proteins, promote the usage of proximal APA sites at the transcriptome level. SNRNP70 can drive the phase transition of PABPN1 from droplet to aggregate, which may reduce the repressive effects of PABPN1 on the proximal APA sites. Additionally, SNRNP70 can also promote the proximal APA sites by recruiting CPSF6, suggesting that the function of CPSF6 on APA is related with other RNA-binding proteins and cell context-dependent. Consequently, these results reveal that, on the contrary to U1 snRNP complex, the free proteins of U1 snRNP complex can promote proximal APA sites through the interaction with 3' end processing machinery.

Nuclear m6 A reader YTHDC1 suppresses proximal alternative polyadenylation sites by interfering with the 3' processing machinery.

N6-methyladenosine (m6 A) and alternative polyadenylation (APA) are important regulators of gene expression in eukaryotes. Recently, it was found that m6 A is closely related to APA. However, the molecular mechanism of this new APA regulation remains elusive. Here, we show that YTHDC1, a nuclear m6 A reader, can suppress proximal APA sites and produce longer 3' UTR transcripts by binding to their upstream m6 A sites. YTHDC1 can directly interact with the 3' end processing factor FIP1L1 and interfere with its ability to recruit CPSF4. Binding to the m6 A sites can promote liquid-liquid phase separation of YTHDC1 and FIP1L1, which may play an important role in their interaction and APA regulation. Collectively, YTHDC1 as an m6 A "reader" links m6 A modification with pre-mRNA 3' end processing, providing a new mechanism for APA regulation.

Differences in Ectopic Pregnancy Rates between Fresh and Frozen Embryo Transfer after In Vitro Fertilization: A Large Retrospective Study.

Ectopic pregnancy (EP) is increasingly found in women treated with in vitro fertilization and embryo transfer (IVF−ET). With the development of the freeze-all policy in reproductive medicine, it is controversial whether frozen embryo transfer (FET) could reduce the rate of EP. In this single-center, large-sample retrospective study, we analyzed 16,048 human chorionic gonadotrophin (hCG)-positive patients who underwent fresh embryo transfer (ET) or FET cycles between January 2013 and March 2022. Throughout the study, the total EP rate was 2.09% (336/16,048), 2.16% (82/3803) in the ET group, and 2.07% (254/12,245) in the FET group. After adjustment for age, infertility causes, and other confounding factors, logistic regression results showed no statistical difference in EP rates between FET and ET groups (odds ratio (OR) 0.93 (0.71−1.22), p > 0.05). However, among the 3808 patients who underwent fresh ET cycles, the OR for EP was significantly lower in the long agonist protocol group than in the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol group (OR 0.45 (0.22−0.93), p < 0.05). Through a large retrospective study, we demonstrated a slightly lower EP rate in FET cycles than in fresh ET cycles, but there was no significant difference. The long agonist protocol in ET cycles had a significantly lower risk of EP than the GnRH-ant protocol.