The Making of a Flight Feather: Bio-architectural Principles and Adaptation.

The evolution of flight in feathered dinosaurs and early birds over millions of years required flight feathers whose architecture features hierarchical branches. While barb-based feather forms were investigated, feather shafts and vanes are understudied. Here, we take a multi-disciplinary approach to study their molecular control and bio-architectural organizations. In rachidial ridges, epidermal progenitors generate cortex and medullary keratinocytes, guided by Bmp and transforming growth factor ß (TGF-ß) signaling that convert rachides into adaptable bilayer composite beams. In barb ridges, epidermal progenitors generate cylindrical, plate-, or hooklet-shaped barbule cells that form fluffy branches or pennaceous vanes, mediated by asymmetric cell junction and keratin expression. Transcriptome analyses and functional studies show anterior-posterior Wnt2b signaling within the dermal papilla controls barbule cell fates with spatiotemporal collinearity. Quantitative bio-physical analyses of feathers from birds with different flight characteristics and feathers in Burmese amber reveal how multi-dimensional functionality can be achieved and may inspire future composite material designs. VIDEO ABSTRACT.

Pseudorabies virus usurps non-muscle myosin heavy chain IIA to dampen viral DNA recognition by cGAS for antagonism of host antiviral innate immunity.

Alphaherpesvirus pseudorabies virus (PRV) causes severe economic losses to the global pig industry and has garnered increasing attention due to its broad host range including humans. PRV has developed a variety of strategies to antagonize host antiviral innate immunity. However, the underlying mechanisms have not been fully elucidated. In our previous work, we demonstrated that non-muscle myosin heavy chain IIA (NMHC-IIA), a multifunctional cytoskeleton protein, attenuates innate immune responses triggered by RNA viruses. In the current study, we reported a previously unrecognized role of NMHC-IIA in counteracting PRV-induced cyclic GMP-AMP synthase (cGAS)-dependent type I interferon (IFN-I) production. Mechanistically, PRV infection led to an elevation of NMHC-IIA, strengthening the interaction between poly (ADP-ribose) polymerase 1 (PARP1) and cGAS. This interaction impeded cGAS recognition of PRV DNA and hindered downstream signaling activation. Conversely, inhibition of NMHC-IIA by Blebbistatin triggered innate immune responses and enhanced resistance to PRV proliferation both in vitro and in vivo. Taken together, our findings unveil that PRV utilizes NMHC-IIA to antagonize host antiviral immune responses via impairing DNA sensing by cGAS. This in-depth understanding of PRV immunosuppression not only provides insights for potential PRV treatment strategies but also highlights NMHC-IIA as a versatile immunosuppressive regulator usurped by both DNA and RNA viruses. Consequently, NMHC-IIA holds promise as a target for the development of broad-spectrum antiviral drugs.IMPORTANCECyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis plays a vital role in counteracting alphaherpesvirus infections. Alphaherpesviruses exploit various strategies for antagonizing cGAS-STING-mediated antiviral immune responses. However, limited examples of pseudorabies virus (PRV)-caused immunosuppression have been documented. Our findings reveal a novel role of non-muscle myosin heavy chain IIA (NMHC-IIA) in suppressing PRV-triggered innate immune responses to facilitate viral propagation both in vitro and in vivo. In detail, NMHC-IIA recruits poly (ADP-ribose) polymerase 1 (PARP1) to augment its interaction with cGAS, which impairs cGAS recognition of PRV DNA. Building on our previous demonstration of NMHC-IIA's immunosuppressive role during RNA virus infections, these findings indicate that NMHC-IIA acts as a broad-spectrum suppressor of host antiviral innate immunity in response to both DNA and RNA viruses. Therefore, NMHC-IIA will be a promising target for the development of comprehensive antiviral strategies.

Liposomal STAT3-Degrading PROTAC Prodrugs Promote Anti-Hepatocellular Carcinoma Immunity via Chemically Reprogramming Cancer Stem Cells.

Cancer stem cells (CSCs) with hyperactivated signal transducer and activator of transcription 3 (STAT3) are a major driver of hepatocellular carcinoma (HCC). Herein, we report a nanointegrative proteolysis-targeting chimera (PROTAC)-based STAT3 degradation strategy that enables efficient chemical reprogramming of HCC-associated CSCs, which potently inhibits CSC growth while evoking anti-HCC immune responses. The PROTAC prodrug was synthesized by conjugating the STAT3 binding domain (inS3) with a thioketal-caged E3 ligase ligand (VL-TK) via an oligo(ethylene glycol) linker (OEG) with tuned length and flexibility and encapsulating it in cRGD-modified cationic liposomes for CSC-targeted delivery while facilitating their lysosomal escape. The PROTAC prodrugs were activated by the upregulated ROS levels in CSCs and efficiently degraded STAT3 for chemical reprogramming, which would not only impair their stemness features but also remodel the immunosuppressive TME into an immunosupportive state to boost anti-HCC immunity. This strategy provides an approach for improving HCC treatment in clinics.

Dynamic crystallography reveals spontaneous anisotropy in cubic GeTe.

Cubic energy materials such as thermoelectrics or hybrid perovskite materials are often understood to be highly disordered1,2. In GeTe and related IV-VI compounds, this is thought to provide the low thermal conductivities needed for thermoelectric applications1. Since conventional crystallography cannot distinguish between static disorder and atomic motions, we develop the energy-resolved variable-shutter pair distribution function technique. This collects structural snapshots with varying exposure times, on timescales relevant for atomic motions. In disagreement with previous interpretations3-5, we find the time-averaged structure of GeTe to be crystalline at all temperatures, but with anisotropic anharmonic dynamics at higher temperatures that resemble static disorder at fast shutter speeds, with correlated ferroelectric fluctuations along the <100>c direction. We show that this anisotropy naturally emerges from a Ginzburg-Landau model that couples polarization fluctuations through long-range elastic interactions6. By accessing time-dependent atomic correlations in energy materials, we resolve the long-standing disagreement between local and average structure probes1,7-9 and show that spontaneous anisotropy is ubiquitous in cubic IV-VI materials.

Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

Polydopamine nanoplatform with near infrared light and pH dual stimuli-responsive for chemo-photothermal cancer therapy.

Photothermal agent accompanying with thermally responsive materials, displays well controlled drug release property, which is well-received as an outstanding design strategy for simultaneous photothermal/chemotherapy in cancer. Cyanine dye, as the prestigious photothermal agent has shown great potential due to its preeminent near-infrared absorbance and excellent thermal conversion efficiency. However, their inherent defect such as inferior photothermal stability, high leakage risk and poor therapy efficacy limit their further application in cancer therapy. Hence, a facile and universal strategy to make up these deficiencies is developed. Chemotherapeutic drug DOX and cyanine dye were loaded into polydopamine (PDA) nanoparticles. The PDA encapsulation dramatically improved the photothermal stability of cyanine dye. Attributed by the PDA structure feature, the thermo-sensitive small molecule glyamine (Gla) is introduced into the PDA surface to lessen leakage. The Gla can form a dense encapsulation layer on the dopamine surface through hydrogen bond. This newly fabricated Cyanine/DOX@PDA-Gla nanopaltform is characterized with NIR light/pH dual-responsive property, high NIR photothermal conversion performance and fluorescence guided chemo-photothermal therapy.

Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity.

cGAS-STING signaling is a central component in the therapeutic action of most existing cancer therapies. The accumulated knowledge of tumor immunoregulatory network in recent years has spurred the development of cGAS-STING agonists for tumor treatment as an effective immunotherapeutic strategy. However, the clinical translation of these agonists is thus far unsatisfactory because of the low immunostimulatory efficacy and unrestricted side effects under clinically relevant conditions. Interestingly, the rational integration of biomaterial technology offers a promising approach to overcome these limitations for more effective and safer cGAS-STING-mediated tumor therapy. Herein, we first outline the cGAS-STING signaling axis and generally discuss its association with tumors. We then symmetrically summarize the recent progress in those biomaterial-based cGAS-STING agonism strategies to generate robust antitumor immunity, categorized by the chemical nature of those cGAS-STING stimulants and carrier substrates. Finally, a perspective is provided to discuss the existing challenges and potential opportunities in cGAS-STING modulation for tumor therapy.

Young osteocyte-derived extracellular vesicles facilitate osteogenesis by transferring tropomyosin-1.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. RESULTS: Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. CONCLUSIONS: Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis.

Environmental antibiotics exposure and childhood obesity: A cross-sectional case-control study.

Children's exposures to environmental antibiotics are a major public health concern. However, limited data are available on the effects of environmental antibiotic exposures on childhood obesity. Our study aimed to explore this relationship. We conducted a cross-sectional case-control study nested in a population-based survey of primary school students, including 1855 obese and 1875 random selected control children. A total of 10 antibiotics in urine samples were measured by liquid chromatography-tandem mass spectrometry. Multivariable survey logistic regression was used to assess the associations between environmental antibiotics exposures and childhood obesity. After adjusting for potential confounders, increased odds of obesity were observed in children exposed to tetracycline (OR = 1.31, 95% CI: 1.09-1.57) and sulfamonomethoxine (OR = 1.43, 95% CI: 1-2.05). Comparing none (

An Adaptive Deconvolution Method with Improve Enhanced Envelope Spectrum and Its Application for Bearing Fault Feature Extraction.

To address the problem that complex bearing faults are coupled to each other, and the difficulty of diagnosis increases, an improved envelope spectrum-maximum second-order cyclostationary blind deconvolution (IES-CYCBD) method is proposed to realize the separation of vibration signal fault features. The improved envelope spectrum (IES) is obtained by integrating the part of the frequency axis containing resonance bands in the cyclic spectral coherence function. The resonant bands corresponding to different fault types are accurately located, and the IES with more prominent target characteristic frequency components are separated. Then, a simulation is carried out to prove the ability of this method, which can accurately separate and diagnose fault types under high noise and compound fault conditions. Finally, a compound bearing fault experiment with inner and outer ring faults is designed, and the inner and outer ring fault characteristics are successfully separated by the proposed IES-CYCBD method. Therefore, simulation and experiments demonstrate the strong capability of the proposed method for complex fault separation and diagnosis.

Calcium Phosphate-Based Nanoformulation Selectively Abolishes Phenytoin Resistance in Epileptic Neurons for Ceasing Seizures.

Phenytoin (PHT) is a first-line antiepileptic drug in clinics, which could decrease neuronal bioelectric activity by blocking the voltage-operated sodium channels. However, the intrinsically low blood-brain-barrier (BBB)-crossing capability of PHT and upregulated expression level of the efflux transporter p-glycoprotein (P-gp) coded by the gene Abcb1 in epileptic neurons limit its efficacy in vivo. Herein, a nanointegrated strategy to overcome PHT resistance mechanisms for enhanced antiepileptic efficacy is reported. Specifically, PHT is first incorporated into calcium phosphate (CaP) nanoparticles through biomineralization, followed by the surface modification of the PEGylated BBB-penetrating TAT peptide. The CaP@PHT-PEG-TAT nanoformulation could effectively cross the BBB to be taken in by epileptic neurons. Afterward, the acidic lysosomal environment would trigger their complete degradation to release Ca2+ and PHT into the cytosol. Ca2+ ions would inhibit mitochondrial oxidative phosphorylation to reverse cellular hypoxia to block hypoxia-inducible factor-1α (Hif1α)-Abcb1-axis, as well as disrupt adenosine triphosphate generation, leading to simultaneous suppression of the expression and drug efflux capacity of P-gp to enhance PHT retention. This study offers an approach for effective therapeutic intervention against drug-resistant epilepsy.

Modulation of Vacancy Defects and Texture for High Performance n-Type Bi2 Te3 via High Energy Refinement.

The carrier concentration in n-type layered Bi2 Te3 -based thermoelectric (TE) material is significantly impacted by the donor-like effect, which would be further intensified by the nonbasal slip during grain refinement of crushing, milling, and deformation, inducing a big challenge to improve its TE performance and mechanical property simultaneously. In this work, high-energy refinement and hot-pressing are used to stabilize the carrier concentration due to the facilitated recovery of cation and anion vacancies. Based on this, combined with SbI3 doping and hot deformation, the optimized carrier concentration and high texture degree are simultaneously realized. As a result, a peak figure of merit (zT) of 1.14 at 323 K for Bi2 Te2.7 Se0.3  + 0.05 wt.% SbI3 sample with the high bending strength of 100 Mpa is obtained. Furthermore, a 31-couple thermoelectric cooling device consisted of n-type Bi2 Te2.7 Se0.3  + 0.05 wt.% SbI3 and commercial p-type Bi0.5 Sb1.5 Te3 legs is fabricated, which generates the large maximum temperature difference (ΔTmax ) of 85 K at a hot-side temperature of 343 K. Thus, the discovery of recovery effect in high energy refinement and hot-pressing has significant implications for improving TE performance and mechanical strength of n-type Bi2 Te3 , thereby promoting its applications in harsh conditions.

PGC-1α Affects Epileptic Seizures by Regulating Mitochondrial Fusion in Epileptic Rats.

BACKGROUND: Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), regulated by AMPK, is an important regulator of mitochondrial fusion. At present, whether the AMPK/PGC-1α signaling pathway regulates mitochondrial dynamics in epileptic rats is still unknown. METHODS: Adult male Sprague-Dawley (SD) rats were randomly divided into fourgroups: the control group (0.9% saline, n = 5), the EP groups (lithium-pilocarpine was used to induce epilepsy, and tissues were harvested at 6 and 24 h, every time point, n = 5), the EP + Compound C group (the specific inhibitor of PGC-1α, 15 mg/kg in 2% DMSO, n = 5), and the EP + DMSO group (0.9% saline + 2% DMSO, n = 5). To investigate whether PGC-1α participates in seizures by regulating the expression of mitofusin1/2(MFN1/2)in rats. RESULTS: In this study, the behavioral results indicate that the seizure susceptibility of the rats to epilepsy was increased when the expression of PGC-1α was inhibited. Subsequently, Western blot results suggested that the expression level of both MFN1 and MFN2 in the hippocampus was higher at 6 and 24 h after an epileptic seizure. Besides, the expression of PGC-1α and MFN2 was significantly decreased in the hippocampus when the epileptic rats were treated with Compound C. Furthermore, the immunofluorescence analysis of the localization of MFN1/2 and PGC-1α showed that MFN1/2 was mainly expressed in neurons but not astrocytes in the hippocampus and cerebral cortex of rats. Meanwhile, PGC-1α colocalized with the excitatory post-synaptic marker PSD95, suggesting that PGC-1α may regulate the seizure susceptibility of the rats by mediating excitatory post-synaptic signaling. CONCLUSION: The AMPK/PGC-1α signaling pathway may play an important role in the lithium-pilocarpine-induced epileptic rat model by mediating the expression of fusion proteins.

Etiological subgroups of term small-for-gestational-age and childhood health outcomes.

BACKGROUND: Small-for-gestational-age (SGA) has a heterogeneous etiology. Our study aimed to examine the childhood health outcomes of etiology-distinct term SGA subgroups. METHODS: Data from the Collaborative Perinatal Project were used. The etiological factors of SGA were categorized into five groups: maternal, fetal, placental, environmental and physiological factors. Primary child outcomes included low IQ and growth restriction. A total of 8417 term infants were eligible. RESULTS: Compared with AGA, SGA children due to fetal factors had the highest risk of low IQ (aOR = 1.94, 95% CI: 1.45-2.59). SGA infants due to physiological factors had the highest risk of growth restriction (aOR = 6.04, 95% CI: 3.93-9.27). SGA children had a higher risk of growth restriction with the aOR ranging from 3.05 (95% CI: 2.36-3.96) to 5.77 (95% CI: 4.29-7.75) for the number of risk factors that the SGA infants had from 1 to 5. SGA children with any risk factor were associated with a higher risk of lower IQ with the aOR ranging from 1.59 (95% CI: 1.31-1.94) to 1.96 (95% CI: 1.50-2.55). SGA without the five types of etiologies was not associated with adverse child outcomes except for growth restriction (aOR = 3.82, 95% CI: 2.62-5.55). CONCLUSION: Term SGA of different etiologies may lead to different child health outcomes. IMPACT: Our study found that SGA of different etiologies may lead to different child health outcomes. Compared with AGA, SGA children due to fetal factors had the highest risk of low IQ. SGA infants due to physiological factors had the highest risk of growth restriction. SGA babies should not be treated the same. In the era of precision medicine, our findings may help pediatricians and parents better manage SGA babies according to different etiologies and the number of risk factors.

Small-for-gestational-age and predictors of HOMA indices, leptin and adiponectin in infancy.

AIM: To assess whether small-for-gestational-age (SGA) - an indicator of poor fetal growth, may affect metabolic health biomarkers in infancy and explore the predictors. METHODS: This was a nested matched (1:2) prospective observational study of 65 SGA (birth weight < 10th percentile) and 130 optimal-for-gestational-age (OGA, birth weight 25th-75th percentiles, control) infants in the 3D birth cohort with subjects recruited in Canada from 1 May 2010 to 31 August 2012. The outcomes included homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß), circulating leptin and adiponectin concentrations at age 2 years. RESULTS: HOMA-IR, HOMA-ß, leptin and adiponectin concentrations were similar in SGA versus OGA infants. Female sex and accelerated growth in length during mid-infancy (3-12 months) were associated with higher HOMA-IR. Caucasian ethnicity and decelerated growth in weight during late infancy (12-24 months) were associated with lower HOMA-IR. Current BMI was positively associated with circulating adiponectin in SGA infants only (+13.4% [4.0%-23.7%] per BMI z score increment). CONCLUSION: Insulin resistance and secretion, circulating leptin and adiponectin levels were normal in SGA subjects in infancy at age 2 years. The novel observation in SGA-specific positive association between current BMI and circulating adiponectin suggests dysfunctional adiposity-adiponectin negative feedback loop development during infancy in SGA subjects.

The association between maternal urinary Bisphenol A levels and neurodevelopment at age 2 years in Chinese boys and girls: A prospective cohort study.

The impact of maternal exposure to Bisphenol A on child cognitive development as well as its sex dimorphism remains uncertain. This study used data of 215 mothers and their children from a birth cohort in Shanghai. Urinary BPA were measured in spot urine samples of mothers at late pregnancy and children at age 2 years. Cognitive development was evaluated by Ages & Stages Questionnaires, Third Edition (ASQ-3) at age 2 years. Urinary BPA was detectable in 98.9% of mothers (geometric mean, GM: 2.6 µg/g. creatinine) and 99.8% children (GM: 3.4 µg/g. creatinine). Relative to the low and medium BPA tertiles, high tertile of maternal urinary BPA concentrations were associated with 4.8 points lower (95% CI: -8.3, -1.2) in gross motor and 3.7 points lower (95% CI: -7.4, -0.1) in problem-solving domain in girls only, with adjustment for maternal age, maternal education, pre-pregnancy BMI, passive smoking during pregnancy, parity, delivery mode, birth-weight for gestational age, child age at ASQ-3 test. This negative association remained with additional adjustment for child urinary BPA concentrations at age 2 years. No association was observed in boys. These results suggested the sex-dimorphism on the associations of maternal BPA exposure with gross motor and problem-solving domains in children at age 2 years. This study also indicated that optimal early child development should start with a healthy BPA-free "in utero" environment.

Urinary antibiotics concentrations, their related affecting factors and infant growth in the first 6 months of life: A prospective cohort study.

Antibiotic exposure even in low-dose could have potential adverse health effects, especially during early life. There is a lack of data on antibiotic burdens in early infancy. We aim to assess antibiotic exposure in infants from birth to 6 months of age, their related affecting factors and the association between antibiotic exposure and infancy growth. Urine samples were collected at ages of 3 days, 42 days, 3 months and 6 months from 197 term-born Chinese infants. A total of 33 representative antibiotics were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Urinary antibiotics were detectable in 69.4%, 63.2%, 75.0% and 84.3% of infants at ages of 3 days, 42 days, 3 and 6 months, respectively. The dominant antibiotic categories detected were: Preferred as Veterinary Antibiotics (PVAs), Human Antibiotics (HAs), and Veterinary Antibiotics (VAs). The detectable rates were 30.6%, 45.8%, 58.9%, and 81.4% for PVAs, 34.1%, 20.8%, 28.6%, and 45.1% for HAs, and 36.5%, 12.5%, 6.3%, and 5.9% for VAs, at age 3 days, 42 days, 3 and 6 months, respectively. Urinary concentrations of HAs and preferred as human antibiotics (PHAs) in newborns at age 3 days were not associated with maternal intrapartum antibiotic prophylaxis. Similarly, no associations were observed between urinary antibiotics concentration and antibiotics use in infants at age 42 days or 6 months. The numbers and concentrations of urine detectable antibiotics were similar between infants with exclusive breastfeeding and infants fed with formula or mixed-feeding at all ages of 42 days, 3 and 6 months. At age of 42 days, infants in the low tertile of total antibiotics concentration or with one antibiotic detected had higher weight-for-length Z score and greater head circumference, compared to infants with no antibiotics detected. No associations were found between urinary antibiotics and any of the infant anthropometric measures at age 6 months. In conclusion, urinary antibiotics were detectable in most infants during the first 6 months of life, and PVAs, HAs and VAs were the most commonly detected antibiotics. This suggested the possibility of a foods-originated antibiotics exposure in children. No strong nor consistent associations were found between urinary antibiotic concentration and infant growth at the first six months of life. Still, attention is needed on the adverse health effect of early life exposure to antibiotics in future studies.

Maternal blood concentrations of toxic metal(loid)s and trace elements from preconception to pregnancy and transplacental passage to fetuses.

Intrauterine exposure to heavy metals may adversely affect the developing fetus and health later in life, while certain trace elements may be protective. There is limited data on their dynamic fluctuation in circulating concentration of women from preconception to pregnancy and the degree of transplacental passage to fetus. Such information is critically needed for an optimal design of research studies and intervention strategies. In the present study, we profiled the longitudinal patterns and trajectories of metal(loid)s and trace elements from preconception to late pregnancy and in newborns. We measured whole blood metal(loid)s in women at preconception, 16, 24 and 32 weeks of gestation and in cord blood in 100 mother-newborn pairs. Our data showed that the mean concentrations of mercury (Hg), lead (Pb), rubidium (Rb), manganese (Mn), and iron (Fe) were lower during early-, mid-, and late-pregnancy than at preconception. Copper (Cu), and calcium (Ca) concentrations increased after pregnancy (Cu 798 versus 1353, 1488, and 1464 µg/L). Concentrations at preconception were correlated with those during pregnancy for all examined metal(loid)s. Maternal Hg, Pb, and Se concentrations at late-pregnancy were correlated with those in newborn cord blood in various degrees (correlation coefficients: Hg 0.66, Pb 0.29, Se 0.39). The estimated placental transfer ratio for toxic metal(loid)s ranging from 1.68 (Hg) to 0.18 (Cd). Two trajectory groups were identified for Hg, Pb, Cd, Se concentrations. Hg concentrations may be correlated with maternal education levels. The study is the first to present longitudinal circulating concentration trajectories of toxic metal(loid)s and trace elements from preconception to pregnancy stages. A high degree of transplacental passage was observed in toxic metals Pb and Hg which may pose hazards to the developing fetus.

Analysis of Mechanical Properties and Fatigue Life of Microturbine Angular Contact Ball Bearings under Eccentric Load Conditions.

Angular contact ball bearings are common basic components in rotating machinery. During the operation of the bearing, the rolling slips, resulting in contact sliding friction between it and the raceway, which in turn causes wear in the rolling element and increase in the radial clearance of the bearing. The increase in clearance also affects the stiffness of the bearing, which in turn affects the natural frequency and fatigue life of the bearing. At present, there are few studies on the influence of bearing wear (variation of clearance) on life. In this paper, the finite element model based on the theory of contact mechanics is established for the angular contact ball bearing with medium- and high-speed rotation, and the mechanical properties and fatigue life influenced by the internal action of the bearing are analyzed. The effects of radial load and deflection angle on the mechanical properties and fatigue life of the bearing are also studied. Based on the analysis results of bearing contact mechanical properties and clearance changes, the calculation method of bearing life under rolling element wear is established. The influence of the variation of clearance and preload clearance on bearing life is analyzed, and the optimal preload is obtained. The research results of this paper can provide a theoretical basis for optimizing the installation of angular contact ball bearings, reasonably determining the service conditions, and prolonging the service life of bearings, which is necessary for engineering practice.

Approach to the Quantitative Diagnosis of Rolling Bearings Based on Optimized VMD and Lempel-Ziv Complexity under Varying Conditions.

The quantitative diagnosis of rolling bearings is essential to automating maintenance decisions. Over recent years, Lempel-Ziv complexity (LZC) has been widely used for the quantitative assessment of mechanical failures as one of the most valuable indicators for detecting dynamic changes in nonlinear signals. However, LZC focuses on the binary conversion of 0-1 code, which can easily lose some effective information about the time series and cannot fully mine the fault characteristics. Additionally, the immunity of LZC to noise cannot be insured, and it is difficult to quantitatively characterize the fault signal under strong background noise. To overcome these limitations, a quantitative bearing fault diagnosis method based on the optimized Variational Modal Decomposition Lempel-Ziv complexity (VMD-LZC) was developed to fully extract the vibration characteristics and to quantitatively characterize the bearing faults under variable operating conditions. First, to compensate for the deficiency that the main parameters of the variational modal decomposition (VMD) have to be selected by human experience, a genetic algorithm (GA) is used to optimize the parameters of the VMD and adaptively determine the optimal parameters [k, α] of the bearing fault signal. Furthermore, the IMF components that contain the maximum fault information are selected for signal reconstruction based on the Kurtosis theory. The Lempel-Ziv index of the reconstructed signal is calculated and then weighted and summed to obtain the Lempel-Ziv composite index. The experimental results show that the proposed method is of high application value for the quantitative assessment and classification of bearing faults in turbine rolling bearings under various operating conditions such as mild and severe crack faults and variable loads.