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Background: Fetal overgrowth (large for gestational age, LGA) is associated with an increased risk of maternal and fetal morbidity and adverse health outcomes. Thyroid hormones are key regulators of metabolism during pregnancy and fetal development. Lower maternal free thyroxine (fT4) and higher maternal triglyceride (TG) levels during early pregnancy are associated with higher birth weight. We aimed at examining the mediating role of maternal TG in the association between maternal fT4 and birth weight. Methods: We performed a large prospective cohort study including pregnant Chinese women who were treated at a tertiary obstetric center during the period of January 2016 to December 2018. We included 35,914 participants with complete medical records. We performed causal mediation analysis to decompose the overall effect of fT4 on birth weight and LGA with maternal TG as the mediator. Results: We observed statistically significant associations between maternal fT4, TG levels, and birth weight (all p < 0.0001). Using a four-way decomposition model, we identified a controlled direct effect (coefficient [confidence interval, CI], -0.038 [-0.047 to -0.029], p < 0.0001) that accounted for 63.9% of the total effect, in addition to the other three estimated effects (reference interaction, coefficient [CI] = -0.006 [-0.009 to -0.001], p = 0.008; mediated interaction, coefficient [CI] = 0.0004 [0.000 to 0.001], p = 0.008; and pure indirect effect, coefficient [CI] = -0.009 [-0.013 to -0.005], p < 0.0001) of TG on the association between fT4 and birth weight Z score. Moreover, maternal TG accounted for 21.6% and 20.7% (via mediation) and 13.6% and 41.6% (via maternal fT4 and TG interaction) of the total effect of maternal fT4 on fetal birth weight and LGA, respectively. The proportions of the total associations that could be reduced by "eliminating"the effect of maternal TG were 36.1% for birth weight and 65.1% for LGA, respectively. Conclusions: High maternal TG levels may play substantial mediating roles in the relationship between low fT4 levels in early pregnancy and increased birth weight and a higher risk of LGA. Further, the occurrence of fetal overgrowth may also be influenced by possible synergistic effects between fT4 and TG.

Background: Human chorionic gonadotropin (hCG) is a marker of placental function, which also stimulates the maternal thyroid gland. Maternal thyroid function can be associated with the pathophysiology of gestational diabetes mellitus (GDM). We aimed to study whether there is an association of hCG concentrations in early pregnancy with GDM and whether it is mediated through maternal thyroid hormones. Methods: This study included 18,683 pregnant women presenting at a tertiary hospital in Shanghai, China, between January 2015 and December 2016. GDM was diagnosed using a 2-hour, 75-g, oral glucose tolerance test (OGTT) according to the American Diabetes Association guidelines. Multivariable logistic or linear regression models were used to identify associations, adjusting for maternal age, education level, family history of diabetes, parity, fetal sex, thyroperoxidase antibody (TPOAb) status, and prepregnancy body-mass index. Results: Higher hCG concentrations were associated with a lower plasma glucose level during the OGTT, but not with fasting plasma glucose or hemoglobin A1c concentrations tested during early pregnancy. hCG in early pregnancy was negatively associated with GDM risk (p = 0.027). Mediation analysis identified that an estimated 21.4% of the association of hCG-associated GDM risk was mediated through changes in free thyroxine (fT4) concentrations (p < 0.05). In the sensitivity analysis restricted to TPOAb-positive women, hCG was not associated with GDM (p = 0.452). Conclusions: Higher hCG levels in early pregnancy are associated with a lower risk of GDM. Maternal fT4 may act as an important mediator in this association.

Context Prepregnancy overweight/obesity (OWO) and isolated maternal hypothyroxinemia (IMH) may increase the risk of macrosomia, but little is known about their potential combined effect on macrosomia. Objective The aim of this study was to assess whether prepregnancy OWO and first-trimester IMH have a synergistic effect on the risk of macrosomia. Methods A large prospective cohort study in a Chinese population from January 2016 to December 2018 in a tertiary care center. In total, 34 930 pregnant women were included. The main outcome measure was macrosomia. Results A total of 34 930 participants comprising IMH and euthyroid cases was included in this study. Prepregnancy OWO and first-trimester IMH were independently associated with an increased risk of macrosomia (adjusted odds ratio [OR] 2.48, 95% CI 2.22, 2.78, and adjusted OR 1.65, 95% CI 1.34, 2.01, respectively). The coexistence of prepregnancy OWO and IMH was associated with macrosomia, with an adjusted OR of 5.26 (95% CI 3.9, 7.0) compared with pregnant women without either condition. The additive interaction between prepregnancy OWO and IMH was found to be significant with regard to macrosomia. Conclusion Prepregnancy OWO and IMH in the first trimester may synergistically increase the risk of macrosomia.

Small protein B (SmpB) is an essential molecule in trans-translation which is a universal biological pathway for protein synthesis in bacteria. Trans-translation can release stalled ribosomes from defective mRNAs and target tag-protein fragments for degradation, and then restart protein synthesis. The SmpB-tmRNA complex coordinating with other components of the trans-translation system, plays vital roles in Mycobacterium tuberculosis under both stress conditions and non-replicating conditions. Thus, elucidation of molecular details and dynamic properties of the SmpB-tmRNA interaction is a crucial step towards effectively blocking trans-translation process to shorten the duration of tuberculosis treatment. Here, we report resonance assignments for 1H, 13C and 15N of M. tuberculosis SmpB (MtSmpB, spanning residues 4-133) protein determined by a suite of 2D/3D heteronuclear NMR experiments along with predicted the secondary structure.

The trans-translation system is recognized as an excellent target for developing new drugs to rapidly sterilize Mycobacterium tuberculosis (TB) infection and significantly shorten TB treatment duration. As a vital component of the trans-translation system for rescuing stalled ribosomes, the SmpB protein from Mycobacterium tuberculosis (MtbSmpB, 1-160 a. a.) mediates tmRNA binding to stalled ribosomes through forming a complex with tmRNA. So far, few works have been conducted to prepare, characterize biophysical properties and determine three-dimensional structure for the full-length MtbSmpB protein. In the present work, we successfully expressed and purified the His-tagged full-length MtbSmpB protein in Escherichia coli with a yield of 26.9 mg from 1 L of Luria Bertani medium. We also obtained MtbSmpB with a yield of 18.5 mg from 1 L of M9 minimal medium. The MtbSmpB protein showed a single band in SDS-PAGE with a molecular weight of ∼20 kDa consistent with the measurement from MALDI-TOF-mass spectrometry. The dynamic light scattering experiment indicated that MtbSmpB existed in a monomeric form. Moreover, both circular dichroism and nuclear magnetic resonance (NMR) experiments exhibited that MtbSmpB was well structured, suggesting that it could be feasible to determine its solution structure by NMR spectroscopy. NMR titration experiments showed that MtbSmpB specifically bound to tmRNA. This work lays the essential basis for further determining the solution structure and dynamics of the full-length MtbSmpB protein.

The Yangtze River is one of the most important components of the East Asia river system. In this study, sediments in the Jianghan Basin, middle Yangtze River, were selected for trace element and rare earth element (REE) measurements, in order to decipher information on the change of sediment provenance and evolution of the Yangtze River. According to the elemental variations, the late Cenozoic sediments of the Jianghan Basin could be divided into four parts. During 2.68–2.28 Ma and 1.25–0 Ma, provenance of the sediments was consistent, whereas sediments were derived from variable sources during 2.28–1.25 Ma. Comparison of the elemental compositions between the Pliocene and Quaternary sediments revealed a change in sediment source from a more felsic source area to a more basic source area around the Pliocene–Quaternary boundary. Input from the Emeishan LIP should account for this provenance change. Based on the provenance analysis of sediments in the Jianghan Basin, we infer that the Yangtze River developed into a large river with its drainage basin extended to the Emeishan LIP no later than the Pliocene–Quaternary boundary.

Pyrazinamide (PZA) is a first-line drug for tuberculosis (TB) treatment and is responsible for shortening the duration of TB therapy. The mode of action of PZA remains elusive. RpsA, the ribosomal protein S1 of Mycobacterium tuberculosis (Mtb), was recently identified as a target of PZA based on its binding activity to pyrazinoic acid (POA), the active form of PZA. POA binding to RpsA led to the inhibition of trans-translation. However, the nature of the RpsA-POA interaction remains unknown. Key questions include why POA exhibits an exquisite specificity to RpsA of Mtb and how RpsA mutations confer PZA resistance. Here, we report the crystal structures of the C-terminal domain of RpsA of Mtb and its complex with POA, as well as the corresponding domains of two RpsA variants that are associated with PZA resistance. Structural analysis reveals that POA binds to RpsA through hydrogen bonds and hydrophobic interactions, mediated mainly by residues (Lys303, Phe307, Phe310 and Arg357) that are essential for tmRNA binding. Conformational changes induced by mutation or sequence variation at the C-terminus of RpsA abolish the POA binding activity. Our findings provide insights into the mode of action of PZA and molecular basis of PZA resistance associated with RpsA mutations.

The first-principles method has been performed to investigate the phase transition, elastic, thermodynamic and superconductivity properties of lanthanum monosulphide (LaS) under pressure. A structural phase transition from the NaCl-type (B1) to CsCl-type (B2) structure is found to occur at around 16.8 GPa. The calculated ground state properties such as lattice constants, bulk modulus, and Debye temperatures are in good agreement with experimental data. Finally, the pressure dependence of the theoretical elastic constants and elastic modulus of LaS has been studied. The observations show that LaS is mechanically stable not only in B1 phase below 8.77 GPa but also in B2 phase under high pressure. LaS is ductile in B1 phase while brittle in B2 phase. The present observation of physical properties in B2 phase of LaS needs validation by future experimental.

Pyrazinamide (PZA) is a first-line drug for tuberculosis (TB) treatment and is responsible for shortening the duration of TB therapy. The mode of action of PZA remains elusive. RpsA, the ribosomal protein S1 of Mycobacterium tuberculosis (Mtb), was recently identified as a target of PZA based on its binding activity to pyrazinoic acid (POA), the active form of PZA. POA binding to RpsA led to the inhibition of trans-translation. However, the nature of the RpsA-POA interaction remains unknown. Key questions include why POA exhibits an exquisite specificity to RpsA of Mtb and how RpsA mutations confer PZA resistance. Here, we report the crystal structures of the C-terminal domain of RpsA of Mtb and its complex with POA, as well as the corresponding domains of two RpsA variants that are associated with PZA resistance. Structural analysis reveals that POA binds to RpsA through hydrogen bonds and hydrophobic interactions, mediated mainly by residues (Lys303, Phe307, Phe310 and Arg357) that are essential for tmRNA binding. Conformational changes induced by mutation or sequence variation at the C-terminus of RpsA abolish the POA binding activity. Our findings provide insights into the mode of action of PZA and molecular basis of PZA resistance associated with RpsA mutations.

Based on the combination of the ordinal theory and the set pair analysis theory, a novel method called ordinal set pair analysis model (O-SPAM) is proposed to simplify the process of runoff prediction and improve the prediction precision. The annual runoff data of fifty-two years from 1956 to 2007 of a certain reservoir in Liao River basin are used to prove the prediction effect of O-SPAM. The results indicate that seven relative errors which account for 70% of the total prediction number are less than 5%; one which accounts for 10% of the total number is between 5 and 10%; while the others which account for 20% of the total number are between 10 and 15%. All the relative errors are less than 20%, which meets the required precision of the annual runoff prediction in “Standard for hydrological information and hydrological forecasting”, indicating that the model can predict the runoff accurately. The study demonstrates that O-SPAM is of clear principle, simple structure, easy calculation, and good prediction precision, and the model is applied to the annual runoff prediction.