Binuclear Enamino-Oxazolinate Rare-Earth Metal Complexes: Synthesis and Their Catalytic Performance in Isoprene Polymerization.

We have synthesized a series of binuclear rare-earth metal complexes bearing the newly designed enamino-oxazolinate ligands that feature bridging para-phenyl, meta-phenyl, 1,5-naphthalenyl, and 1,5-anthracenyl moieties. NMR and X-ray diffraction analyses confirmed the binuclear structures of the obtained complexes with two enamino-oxazolinate-metal units located at a trans position against the bridged aryl plane. After activation by [Ph3C][B(C6F5)4], all the rare-earth metal complexes served as efficient catalysts for isoprene polymerization, producing polymers with high cis-1,4 regularity (up to 96.1%) and high molecular weight. The steric and electronic effects exerted on the active metal centers, as well as the radius of metal centers, were the major contributing factors for determining both the catalytic activity and cis-1,4-selectivity of the binuclear catalytic systems. Compared to its mononuclear analogue, the binuclear yttrium catalytic system with a para-phenyl bridge exhibited a higher thermostability and catalytic efficiency during polymerization, revealing a special binuclear effect in this binuclear catalytic system.

The U-shaped association between remnant cholesterol and risk of all-cause and cardiovascular deaths in diabetic adults: Findings from NHANES 1999-2018.

BACKGROUND AND AIMS: We aimed to explore the association between remnant cholesterol (RC) level and risks of all-cause and cardiovascular deaths among American diabetic adults. METHODS AND RESULTS: The data of 4,095 diabetic participants from the National Health and Nutrition Examination Survey (1999-2018) were included for analysis. Deaths were ascertained till December 31, 2019. RC level associated with death was assessed on a continuous scale with restricted cubic splines and by pre-defined quartile groups with Cox regression analysis. After a median follow-up of 6.9 years, 1,060 all-cause and 289 cardiovascular deaths occurred. Association between RC and death was U-shaped, and RC level correlated with the lowest risks of both all-cause and cardiovascular deaths was 0.85 mmol/L. After adjusting for confounders, compared with Quartile 3 (0.66-0.93 mmol/L), hazard ratios for all-cause deaths were 1.43 (95%CI 1.18-1.72, P = 0.0002) in Quartile 1 (≤0.47 mmol/L), 1.20 (95%CI 1.00-1.44, P = 0.05) in Quartile 2 (0.47-0.66 mmol/L), and 1.25 (95%CI 1.05-1.49, P = 0.02) in Quartile 4 (>0.93 mmol/L). Higher risk was also observed for cardiovascular deaths in Quartile 1 (HR 1.66, 95%CI 1.15-2.41, P = 0.007), Quartile 2 (HR 1.39, 95%CI 0.97-2.00, P = 0.08), and Quartile 4 (HR 1.54, 95% CI 1.08-2.19, P = 0.02), as compared with Quartile 3. CONCLUSION: In US adults with diabetes, low and high levels of RC were associated with increased risks of all-cause and cardiovascular deaths, and the lowest risk was observed at RC level of 0.85 mmol/L. These findings suggested that maintaining appropriate RC level may help reduce risk of death in diabetic patients.

The effects of climate and soil depth on living and dead bacterial communities along a longitudinal gradient in Chile.

Soil bacterial communities play a critical role in shaping soil stability and formation, exhibiting a dynamic interaction with local climate and soil depth. We employed an innovative DNA separation method to characterize microbial assemblages in low-biomass environments such as deserts and distinguish between intracellular DNA (iDNA) and extracellular DNA (eDNA) in soils. This approach, combined with analyses of physicochemical properties and co-occurrence networks, investigated soil bacterial communities across four sites representing diverse climatic gradients (i.e., arid, semi-arid, Mediterranean, and humid) along the Chilean Coastal Cordillera. The separation method yielded a distinctive unimodal pattern in the iDNA pool alpha diversity, increasing from arid to semi-arid climates and decreasing in humid environments, highlighting the rapid feedback of the iDNA community to increasing soil moisture. In the arid region, harsh surface conditions restrict bacterial growth, leading to peak iDNA abundance and diversity occurring in slightly deeper layers than the other sites. Our findings confirmed the association between specialist bacteria and ecosystem-functional traits. We observed transitions from Halomonas and Delftia, resistant to extreme arid environments, to Class AD3 and the genus Bradyrhizobium, associated with plants and organic matter in humid environments. The distance-based redundancy analysis (dbRDA) analysis revealed that soil pH and moisture were the key parameters that influenced bacterial community variation. The eDNA community correlated slightly better with the environment than the iDNA community. Soil depth was found to influence the iDNA community significantly but not the eDNA community, which might be related to depth-related metabolic activity. Our investigation into iDNA communities uncovered deterministic community assembly and distinct co-occurrence modules correlated with unique bacterial taxa, thereby showing connections with sites and key environmental factors. The study additionally revealed the effects of climatic gradients and soil depth on living and dead bacterial communities, emphasizing the need to distinguish between iDNA and eDNA pools.

Characteristics analysis of Internet pharmacy consultation services for children in southwest China during the post-epidemic era: A cross-sectional study.

AIM: This study aims to examine the features of online pediatric pharmacy consultations in Southwest China, an area with limited medical resources during the post-epidemic era and to explore the factors affecting the dialogue volume in online consultations. METHODS: A cross-sectional study was conducted in southwest China from April 2022 to March 2023. The study encompassed a cohort of 2,526 children, ranging from 0 to 18 years old. The collected data encompassed patient gender, age, weight, department, drugs involved in consultation services, types of questions consulted, consultation start time, and the dialogue volume in online consultations. Descriptive statistics and an ordered multicategorical logistic regression analysis were performed. SPSS 26.0 software was used for data analysis. RESULTS: Among the total Internet pharmacy consultation services offered, the infant group constituted the largest portion (n = 1021). Children with internal medicine concerns have greater online consultation needs (n = 455). The peak usage of Internet pharmacy consultation occurred in the fall at 11:00 a.m. (n = 73). Factors influencing the dialogue volume in online consultations include the non-availability of Chinese medications [P = 0.033, OR = 0.81, 95 % CI (0.67-0.98)], consultation initiation during the spring [P = 0.002, OR = 1.52, 95 % CI(1.17-1.97)] or afternoon [P = 0.012, OR = 1.36, 95 % CI (1.07-1.72)] and weight＜15 kg group [P = 0.038, OR = 2.19, 95 % CI (1.04-4.58)]. CONCLUSION: Our findings provide important information for peers to carry out their work. In the post-epidemic era, emphasis should be placed on addressing concerns related to children's internal medicine and otolaryngology. Optimizing healthcare resource allocation should take into account the time-seasonal variability of children's consultation behaviors. Furthermore, it is recommended to focus on weight＜15 kg children in inquiries, absorb sufficient knowledge about Chinese medicines, and schedule more pharmacists to participate in consultation services during the spring or in every afternoon. These findings help the authorities of online platforms and the National Health Commission to rationalize the allocation of healthcare resources, optimize the quality of service delivery, and develop new policies.

Keypoint regression strategy and angle loss based YOLO for object detection.

The YOLOv4 approach has gained significant popularity in industrial object detection due to its impressive real-time processing speed and relatively favorable accuracy. However, it has been observed that YOLOv4 faces challenges in accurately detecting small objects. Its bounding box regression strategy is rigid and fails to effectively leverage the asymmetric characteristics of objects, limiting its ability to enhance object detection accuracy. This paper proposes an enhanced version of YOLOv4 called KR-AL-YOLO (keypoint regression strategy and angle loss based YOLOv4). The KR-AL-YOLO approach introduces two customized modules: an keypoint regression strategy and an angle-loss function. These modules contribute to improving the algorithm's detection accuracy by enabling more precise localization of objects. Additionally, KR-AL-YOLO adopts an improved feature fusion technique, which facilitates enhanced information flow within the network, thereby further enhancing accuracy performance. Experimental evaluations conducted on the COCO2017 dataset demonstrate the effectiveness of the proposed method. KR-AL-YOLO achieves an average precision of 45.6%, surpassing both YOLOv4 and certain previously developed one-stage detectors. The utilization of keypoint regression strategy and the incorporation of robust feature fusion contribute to superior object detection accuracy in KR-AL-YOLO compared to YOLOv4.

Ultrapure single-band red upconversion luminescence in Er3+ doped sensitizer-rich ytterbium oxide transparent ceramics for solid-state lighting and temperature sensing.

Achieving single-band upconversion (UC) is a challenging but rewarding approach to attain optimal performance in diverse applications. In this paper, we successfully achieved single-band red UC luminescence in Yb2O3: Er transparent ceramics (TCs) through the utilization of a sensitizer-rich design. The Yb2O3 host, which has a maximum host lattice occupancy by Yb3+ sensitizers, facilitates the utilization of excitation light and enhances energy transfer to activators, resulting in improved UC luminescence. Specifically, by shortening the ionic spacing between sensitizer and activator, the energy back transfer and the cross-relaxation process are promoted, resulting in weakening of green energy level 4S3/2 and 2H11/2 emission and enhancement of red energy level 4F9/2 emission. The prepared Yb2O3: Er TCs exhibited superior optical properties with in-line transmittance over 80% at 600 nm. Notably, in the 980nm-excited UC spectrum, green emission does not appear, thus Yb2O3: Er TCs exhibit ultra-pure single band red emission, with CIE coordinates of (0.72, 0.28) and color purity exceeding 99.9%. To the best of our knowledge, this is the first demonstration of pure red UC luminescence in TCs. Furthermore, the luminescent intensity ratio (LIR) technique was utilized to apply this pure red-emitting TCs for temperature sensing. The absolute sensitivity of Yb2O3: Er TCs was calculated to be 0.319% K-1 at 304 K, which is the highest level of optical thermometry based on 4F9/2 levels splitting of Er3+ known so far. The integration between pure red UC luminescence and temperature sensing performance opens up new possibilities for the development of multi-functional smart windows.

QX-type infectious bronchitis virus infection in roosters can seriously injure the reproductive system and cause sex hormone secretion disorder.

Since its discovery, QX-type avian infectious bronchitis virus (IBV) has rapidly spread worldwide and become the most prevalent dominant genotype in Asia and Europe. Currently, although the pathogenicity of QX-type IBV in the reproductive system of hens is widely and deeply understood, its pathogenicity in the reproductive system of roosters remains largely unknown. In this study, 30-week-old specific pathogen-free (SPF) roosters were used to investigate the pathogenicity of QX-type IBV in the reproductive system after infection. The results showed that QX-type IBV infection caused abnormal testicular morphology, moderate atrophy and obvious dilatation of seminiferous tubules, and produced intense inflammation and obvious pathological injuries in the ductus deferens of infected chickens. Immunohistochemistry results showed that QX-type IBV can replicate in spermatogenic cells at various stages and in the mucous layer of the ductus deferens. Further studies showed that QX-type IBV infection affects plasma levels of testosterone, luteinizing hormone, and follicle-stimulating hormone as well as causes changes in transcription levels of their receptors in the testis. Furthermore, the transcription levels of StAR, P450scc, 3ßHSD and 17ßHSD4 also changed during testosterone synthesis after QX-type IBV infection, indicating that the virus can directly affect steroidogenesis. Finally, we found that QX-type IBV infection leads to extensive germ cell apoptosis in the testis. Collectively, our results suggest that QX-type IBV replicates in the testis and ductus deferens, causing severe tissue damage and disruption of reproductive hormone secretion. These adverse events eventually lead to mass germ cell apoptosis in the testis, affecting the reproductive function of roosters.

Functional identification of moss PpGATA1 provides insights into the evolution of LLM-domain B-GATA transcription factors in plants.

B-GATA transcription factors with the LLM domain (LLM-domain B-GATAs) play important roles in developmental processes and environmental responses in flowering plants. Their characterization can therefore provide insights into the structural and functional evolution of functional gene families. Phylogenetic and sequence analysis suggests that LLM-domain B-GATAs evolved from ancestral GATA transcription factors before the divergence of chlorophyte algae and Streptophyta. We compared the function of PpGATA1, a LLM-domain B-GATA gene in moss Physcomitrium patens, with Arabidopsis thaliana counterparts and showed that, in P. patens, PpGATA1 controls growth and greening in haploid gametophytes, while in transgenic Arabidopsis it affects germination, leaf development, flowering time, greening and light responses in diploid sporophytes. These PpGATA1 functions are similar to those of Arabidopsis counterparts, AtGNC, AtGNL and AtGATA17. PpGATA1 was able to complement the role of GNC and GNL in a gnc gnl double mutant, and the LLM domains of PpGATA1 and GNC behaved similarly. The functions of LLM-domain B-GATAs regulating hypocotyl elongation and cotyledon epinasty in flowering plants pre-exist before the divergence of mosses and the lineage leading to flowering plants. This study sheds light on adaption of PpGATA1 and its homologs to new developmental designs during the evolution.

Foliar Application of Spermidine Alleviates Waterlogging-Induced Damages to Maize Seedlings by Enhancing Antioxidative Capacity, Modulating Polyamines and Ethylene Biosynthesis.

Waterlogging is a major threat to maize production worldwide. The exogenous application of spermidine is well known to enhance plant tolerance to abiotic stresses. The role of exogenous spermidine application in waterlogging tolerance in maize was investigated in this study. Two maize varieties (a waterlogging-tolerant variety: Xundan 20 (XD20) and a waterlogging-sensitive variety: Denghai 662 (DH662)) were subjected to waterlogging stress at the seedling stage, and then foliar spraying of 0.75 mM spermidine or purified water. Findings demonstrated lower chlorophyll content, reduced growth indices, considerable increase in superoxide anion (O2-) generation rate, and H2O2/malondialdehyde accumulation in the two maize varieties under waterlogging stress compared to the control treatment. However, the tolerance variety performed better than the sensitive one. Foliar application of spermidine significantly increased antioxidant enzyme activities under waterlogging stress. In addition, the application of spermidine increased polyamine levels and led to the reduction of ethylene levels under waterlogging. Consequences of spermidine application were most apparent for the waterlogging-sensitive cultivar DH662 under waterlogging than the waterlogging-tolerant variety XD20.

Economic value and characteristics of cloud pharmacy for children based on internet hospital in western China during the COVID-19 pandemic: Cross-sectional survey study.

Background: Online health care services have been encouraged by the Chinese government in recent years, and the COVID-19 pandemic catalyzed the rapid growing of internet hospitals. As an integral part of online health care services, little is known about the economic value and characteristics of cloud pharmacy especially for children. This study aimed to reveal the economic value and comprehensive characteristics of pediatric cloud pharmacy during the COVID-19 pandemic in a tertiary children's hospital in western China. Methods: A total of 33,254 online prescriptions over the course of February 2020 through December 2021 were analyzed with respect to the user profiles, diseases, consulting behaviors, distribution of departments, delivery region and distance, drug information and degree of satisfaction. The cost savings for patients calculated lost wages and the high-speed railway fees for transport to and from hospital. Results: A total of 33,254 prescriptions, including 56,216 drugs were delivered to 27 provinces and municipalities of China. The internet cloud pharmacy saved a total of more than RMB 11.17 million in financial costs for patients. Of the 33,254 delivered prescriptions, 50.40% were sent to Chongqing Province, the top 5 provinces for out-of-province prescription deliveries were Sichuan (37.77%), Guizhou (8.00%), Yunnan (1.18%), Hubei (0.66%) and Guangdong (0.42%). In terms of department distribution, neurology (31.7%), respiratory (15.0%) and endocrinology (14.6%) were the top three departments. Epilepsy (16.2%), precocious puberty (10.3%) and asthma (8.7%) were the top three frequently consulted diseases. The peak times of day for online prescriptions occurred at 9 AM and 8 PM. 99.67% of users gave full marks for their internet counseling. Conclusion: The pediatric cloud pharmacy is efficient, cost-saving and convenient for children with chronic disease or mild symptoms during the COVID-19 pandemic. The widespread use of this pediatric cloud pharmacy can help alleviating pressure on offline hospitals and facilitated people's lives beyond geographical and time-related limitations. Further efforts are needed to be made to improve the quality and acceptance of pediatric cloud pharmacy, as well as to regulate and standardize the management of this novel online health care service.

Uterine fibroids increase the risk of preterm birth and other adverse birth events: a systematic review and meta-analysis.

Background: Uterine fibroids may cause preterm birth. This meta-analysis evaluates the effect of uterine fibroids on the risk of preterm birth and other obstetric outcomes. Methods: Using the literature review method, the databases PubMed, Medline, Embase and Central were retrieved to obtain relevant research literature. The selected studies were analyzed and evaluated. The literature was a cohort study or a case-control study of pregnant women as the research object and uterine fibroids as the exposure factor to observe adverse events during pregnancy. The chi-square test was used to test for heterogeneity. Subgroup analyses were used to explore sources of heterogeneity. Publication bias was assessed using Egger's test. Enumeration data were described by odds ratio (OR). Measurement data were described by mean difference (MD). Calculate the confidence interval (CI). Results: A total of 11 studies were included in this study, including 7 cohort studies and 4 case-control studies, with a total of 313,913 women. The probability of uterine fibroids among women was 3.99%. The results of meta-analysis showed that women with uterine fibroids experienced preterm birth <37 weeks (OR =1.43, 95% CI: 1.25 to 1.64, P<0.00001), preterm birth <34 weeks (OR =1.73, 95% CI: 1.34 to 2.25, P<0.0001), premature rupture of membranes (OR =1.38, 95% CI: 1.08 to 1.75, P=0.009), placental abruption (OR =1.60, 95% CI: 1.20 to 2.14, P=0.001), cesarean section (OR =2.09, 95% CI: 1.69 to 2.58, P<0.00001), and postpartum hemorrhage (OR =2.95, 95% CI: 1.86 to 4.66, P<0.00001) were all at higher risk, and the mean gestational age at delivery [mean difference (MD) =-0.58, 95% CI: -0.66 to -0.51, P<0.00001] and birth weight (MD =-117.82, 95% CI: -155.19 to -80.45, P<0.00001) were lower. Egger's test indicated that there was no publication bias among the included studies (P>0.05). Conclusions: Pregnant women with uterine fibroids are at higher risk for preterm birth and other adverse obstetric outcomes and require closer monitoring.

Association between clustering of cardiovascular risk factors and resting heart rate in Chinese population: a cross-sectional study.

BACKGROUND: Epidemiologic studies have explored the association between a single cardiovascular risk factor (CVRF) and resting heart rate (RHR), but the research on the relation of multiple risk factors with RHR remains scarce. This study aimed to explore the associations between CVRFs clustering and the risk of elevated RHR. METHODS: In this cross-sectional study, adults aged 35-75 years from 31 provinces were recruited by the China PEACE Million Persons Projects from September 2015 to August 2020. We focused on seven risk factors: hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, alcohol use, and low physical activity. Multivariate logistic regression was used to calculate odds ratios (OR) for elevated RHR (> 80 beats/min). RESULTS: Among 1,045,405 participants, the mean age was 55.67 ± 9.86 years, and 60.4% of participants were women. The OR (95% CI) for elevated RHR for the groups with 1, 2, 3, 4 and ≥ 5 risk factor were 1.11 (1.08-1.13), 1.36 (1.33-1.39), 1.68 (1.64-1.72), 2.01 (1.96-2.07) and 2.58 (2.50-2.67), respectively (P trend < 0.001). The association between the CVRFs clustering number and elevated RHR was much more pronounced in young males than in other age-sex subgroups. Clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR than those comprising more behavioral risk factors. CONCLUSIONS: There was a significant positive association between the CVRFs clustering number and the risk of elevated RHR, particularly in young males. Compared clusters comprising more behavioral risk factors, clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR. RHR may serve as an indicator of the cumulative effect of multiple risk factors.

Production of indole and hydrogen sulfide by the oxygen-tolerant mutant strain Clostridium sp. Aeroto-AUH-JLC108 contributes to form a hypoxic microenvironment.

In this study, the oxygen-tolerant mutant strain Clostridium sp. Aeroto-AUH-JLC108 was found to produce indole when grown aerobically. The tnaA gene coding for tryptophanase responsible for the production of indole was cloned. The tnaA gene from Aeroto-AUH-JLC108 is 1677 bp and has one point mutation (C36G) compared to the original anaerobic strain AUH-JLC108. Phylogenetic analyses based on the amino acid sequence showed significant homology to that of TnaA from Flavonifractor. Furthermore, we found that the tnaA gene also exhibited cysteine desulfhydrase activity. The production of hydrogen sulfide (H2S) was accompanied by decrease in the amount of the dissolved oxygen in the culture medium. Similarly, the amount of indole produced by strain Aeroto-AUH-JLC108 obviously decreased the oxidation-reduction potential (ORP) in BHI liquid medium. The results demonstrated that production of indole and H2S helped to form a hypoxic microenvironment for strain Aeroto-AUH-JLC108 when grown aerobically.

Fermentation of soymilk by Lactobacillus acidipiscis isolated from Chinese stinky tofu capable of efficiently biotransforming isoflavone glucosides to dihydrodaidzein and dihydrogenistein.

BACKGROUND: The soy isoflavone microbial metabolites dihydrodaidzein (DHD), dihydrogenistein (DHG), equol and 5-hydroxy-equol are generally more biologically active than their precursors daidzein and genistein. Bacteria responsible for isoflavone metabolism have been isolated and identified. Fermented soymilk is a potential functional food; however, there are few lactic acid bacteria capable of metabolizing soy isoflavones. RESULTS: A newly isolated Gram-positive facultative anaerobic bacterium, which was named Lactobacillus acidipiscis HAU-FR7, was isolated from the traditional Chinese fermented soy product 'stinky tofu'. Bacterium strain HAU-FR7 can grow under aerobic conditions and can also convert most of the daidzin and genistin in soymilk into DHD and DHG, respectively. The concentrations of DHD and DHG produced were 183 and 134 µmol L-1 , respectively, after fermentation for 24 h. Strain HAU-FR7 does not produce the biogenic amines cadaverine, putrescine, histamine or tyramine, and an antibiotic susceptibility test showed that HAU-FR7 is sensitive to nine of the ten tested antibiotics, except for vancomycin. Moreover, the 1,1-diphenyl-2- picrylhydrazyl free radical scavenging capacity of soymilk fermented with HAU-FR7 was significantly higher than that of unfermented soymilk. CONCLUSION: A facultative anaerobic lactic acid bacterium, designated Lactobacillus acidipiscis HAU-FR7, is capable of reducing the soy isoflavone glucosides daidzin and genistin in soymilk to DHD and DHG efficiently, even in the presence of atmospheric oxygen. The biotransformation activity of HAU-FR7 grown in soymilk is higher than that in de Man-Rogosa-Sharpe liquid culture medium. © 2022 Society of Chemical Industry.

Effectiveness of a clinical decision support system for hypertension management in primary care: study protocol for a pragmatic cluster-randomized controlled trial.

BACKGROUND: Clinical decision support systems (CDSS) are low-cost, scalable tools with the potential to improve guideline-based antihypertensive treatment in primary care, but their effectiveness needs to be tested, especially in low- and middle-income countries such as China. METHODS: The Learning Implementation of Guideline-based decision support system for Hypertension Treatment (LIGHT) trial is a pragmatic, four-stage, cluster-randomized trial conducted in 94 primary care sites in China. For each city-based stage, sites are randomly assigned to either implementation of the CDSS for hypertension management (which guides doctors' treatment recommendations based on measured blood pressure and patient characteristics), or usual care. Patients are enrolled during the first 3 months after site randomization and followed for 9 months. The primary outcome is the proportion of hypertension management visits at which guideline-based treatment is provided. In a nested trial conducted within the CDSS, with the patient as the unit of randomization, the LIGHT-ACD trial, patients are randomized to receive different initial mono- or dual-antihypertensive therapy. The primary outcome of the LIGHT-ACD trial is the changes in blood pressure. DISCUSSION: The LIGHT trial will provide evidence on the effectiveness of a CDSS for improving guideline adherence for hypertension management in primary care in China. The nested trial, the LIGHT-ACD trial, will provide data on the effect of different initial antihypertensive regimens for blood pressure management in this setting. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: LIGHT (NCT03636334) and LIGHT-ACD (NCT03587103). Registered on 3 July 2018.

Dose-response association between long-term weight loss in young adults and later-life metabolic health.

OBJECTIVE: Long-term weight loss (LTWL) has been shown to be associated with lower metabolic risk in young adults with overweight/obesity. However, the dose-response association is uncertain. METHODS: In a large-scale nationwide screening project in China, the participants aged 35 to 64 years who recalled overweight/obesity at age 25 years and experienced LTWL or maintained stable weight were included. The dose-response association between LTWL from age 25 to screening (35 to 64 years) and the odds of metabolic syndrome at screening were assessed using multivariable adjusted regression models with restricted cubic splines. RESULTS: A total of 40,150 participants (66.4% women) were included. The increment of LTWL was associated with continuously decreased odds of metabolic syndrome. The odds of metabolic syndrome were 0.64 (0.60 to 0.67), 0.42 (0.40 to 0.45), 0.27 (0.25 to 0.29), and 0.15 (0.13 to 0.17) for those with LTWL of 5% to 9.9%, 10% to 14.9%, 15% to 19.9%, and 20% or greater compared with <5% LTWL, respectively. Moreover, the incremental pattern was observed across all population subgroups. CONCLUSIONS: An incremental association between LTWL from young adulthood and odds of later-life metabolic syndrome was observed. Our findings highlight the effective ways to achieve LTWL to improve lifetime metabolic health for young adults with overweight/obesity.

Repurposed major urinary protein pheromones and adult sensory neurons: roles in neuron plasticity and experimental diabetes.

Major urinary proteins (MUPs), members of the broader lipocalin protein family, are classified as pheromones that are excreted in male rodent urine to define conspecific territoriality. In screening for differentially regulated mRNA transcripts in a mouse model of type 1 experimental diabetes mellitus (DM), we identified an unexpected upregulation of several closely related MUP transcripts within diabetic sensory dorsal root ganglia (DRG). Both sexes expressed overall MUP protein content as identified by an antibody widely targeting these upregulated family members, and immunohistochemistry identified expression within neurons, satellite glial cells, and Schwann cells. In dissociated adult sensory neurons, knockdown by an siRNA targeting upregulated MUP mRNAs, enhanced neurite outgrowth, indicating a growth-suppressive role, an impact that was synergistic with subnanomolar insulin neuronal signaling. While MUP knockdown did not generate rises in insulin signaling transcripts, the protein did bind to several mitochondrial and glial targets in DRG lysates. Analysis of a protein closely related to MUPs but that is expressed in humans, lipocalin-2, also suppressed growth, but its impact was unrelated to insulin. In a model of chronic type 1 DM, MUP siRNA knockdown improved electrophysiological and behavioral abnormalities of experimental neuropathy. MUPs have actions beyond pheromone signaling in rodents that involve suppression of growth plasticity of sensory neurons. Its hitherto unanticipated actions overlap with those of lipocalin-2 and may identify a common and widely mediated impact on neuron growth properties by members of the lipocalin family. Knockdown of MUP supports the trophic actions of insulin as a strategy that may improve features of type 1 experimental diabetic neuropathy.NEW & NOTEWORTHY New molecular mechanisms are important to unravel and understand diabetic polyneuropathy, a disorder prevalent in over half of persons with diabetes mellitus (DM). MUPs, members of the lipocalin family of molecules, have an unexpected impact on the plasticity of sensory neurons that are targeted in type 1 experimental diabetic neuropathy. This work explores this potential target in neuropathy in the context of the lipocalin family of molecules.

An Arabidopsis Retention and Splicing complex regulates root and embryo development through pre-mRNA splicing.

Pre-mRNA splicing is an important step in the posttranscriptional processing of transcripts and a key regulator of development. The heterotrimeric retention and splicing (RES) complex plays vital roles in the growth and development of yeast, zebrafish, and humans by mediating pre-mRNA splicing of multiple genes. However, whether the RES complex is conserved in plants and what specific functions it has remain unknown. In this study, we identified Arabidopsis (Arabidopsis thaliana) BUD13 (AtBUD13), GROWTH, DEVELOPMENT AND SPLICING 1 (GDS1), and DAWDLE (DDL) as the counterparts of the yeast RES complex subunits Bud site selection protein 13 (Bud13), U2 snRNP component Snu17 (Snu17), and Pre-mRNA leakage protein 1, respectively. Moreover, we showed that RES is an ancient complex evolutionarily conserved in eukaryotes. GDS1 directly interacts with both AtBUD13 and DDL in nuclear speckles. The BUD13 domain of AtBUD13 and the RNA recognition motif domain of GDS1 are necessary and sufficient for AtBUD13-GDS1 interaction. Mutants of AtBUD13, GDS1, and DDL failed to properly splice multiple genes involved in cell proliferation and showed defects in early embryogenesis and root development. In addition, we found that GDS1 and DDL interact, respectively, with the U2 small nuclear ribonucleoproteins auxiliary factor AtU2AF65B and the NineTeen Complex-related splicing factor SKIP, which are essential for early steps of spliceosome assembly and recognition of splice sites. Altogether, our work reveals that the Arabidopsis RES complex is important for root and early embryo development by modulating pre-mRNA splicing.