Comparison of temporomandibular joints in relation to ages and vertical facial types in skeletal class II female patients: a multiple-cross-sectional study.

BACKGROUND: The temporomandibular joint (TMJ) is closely related to the dynamic balance and stability of mandibular function and orthodontic treatment. Skeletal class II female patients are thought to be at high risk for TMJ disease. The relationship between the TMJ and craniofacial structures is still controversial. This study compared the morphology and position of the TMJ in skeletal class II adolescents and adults with various vertical facial types using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: A total of 117 skeletal class II patients were divided into three groups according to the FH-GoGn angle (hypodivergent, normodivergent and hyperdivergent), with 40 class I normodivergent patients serving as controls. Each group contained two age subgroups (adolescents: 11-14 years old, adults: 18-35 years old). The size (condylar length, height, long and short axis diameter, glenoid fossa width and depth) and shape (condylar neck inclination, condylar head angle and long axis angle, articular eminence inclination) of the condyle and fossa, joint space (anterior, superior, posterior, mesial and lateral), and position of the fossa (vertical, transverse, and anteroposterior distance) and condyle were measured and compared using CBCT. RESULTS: Class II hypodivergent patients exhibited the greatest condylar length, height, and long- and short-axis diameter; steepest articular eminence; deepest fossa depth; largest superior, mesial and lateral joint spaces; and highest fossa position in both age groups. The manifestations of class II hyperdivergent patients were mostly the opposite. In adults, except for the condylar long axis angle, the measurements of the condyle increased differently among skeletal patterns, while the measurements of the fossa decreased, as the joint spaces and fossa position remained approximately stable compared with those in adolescents. CONCLUSION: The vertical skeletal pattern, rather than the class II sagittal skeletal pattern, may be the main factor affecting the morphology and position of the TMJ. Attention should be given to the TMJ area in hyperdivergent patients with a relatively poor-fit condyle-fossa relationship. The changes in the TMJ with age were mainly morphological rather than positional and varied with skeletal pattern.

Effects of Root-Root Interactions on the Physiological Characteristics of Haloxylon ammodendron Seedlings.

The root traits and response strategies of plants play crucial roles in mediating interactions between plant root systems. Current research on the role of root exudates as underground chemical signals mediating these interactions has focused mainly on crops, with less attention given to desert plants in arid regions. In this study, we focused on the typical desert plant Haloxylon ammodendron and conducted a pot experiment using three root isolation methods (plastic film separation, nylon mesh separation, and no separation). We found that (1) as the degree of isolation increased, plant biomass significantly increased (p < 0.05), while root organic carbon content exhibited the opposite trend; (2) soil electrical conductivity (EC), soil total nitrogen (STN), soil total phosphorus (STP), and soil organic carbon (SOC) were significantly greater in the plastic film and nylon mesh separation treatments than in the no separation treatment (p < 0.05), and the abundance of Proteobacteria and Actinobacteriota was significantly greater in the plastic film separation treatment than in the no separation treatment (p < 0.05); (3) both plastic film and nylon mesh separations increased the secretion of alkaloids derived from tryptophan and phenylalanine in the plant root system compared with that in the no separation treatment; and (4) Pseudomonas, Proteobacteria, sesquiterpenes, triterpenes, and coumarins showed positive correlations, while both pseudomonas and proteobacteria were significantly positively correlated with soil EC, STN, STP, and SOC (p < 0.05). Aurachin D was negatively correlated with Gemmatimonadota and Proteobacteria, and both were significantly correlated with soil pH, EC, STN, STP, and SOC. The present study revealed strong negative interactions between the root systems of H. ammodendron seedlings, in which sesquiterpenoids, triterpenoids, coumarins, and alkaloids released by the roots played an important role in the subterranean competitive relationship. This study provides a deeper understanding of intraspecific interactions in the desert plant H. ammodendron and offers some guidance for future cultivation of this species in the northwestern region of China.

Cyfluthrin exposure during pregnancy causes neurotoxicity in offspring-Ca2+ overload via IP3R-GRP75-VDAC1 pathway.

Cyfluthrin (Cy) is a widely used pyrethroid insecticide. There is growing evidence that Cy can cause damage to the nervous, reproductive, and immune systems, but there is limited evidence on the potential effects of maternal Cy exposure on offspring. A model of maternal Cy exposure was used to assess its neurobehavioral effects on young-adult offspring. We found that gestational Cy exposure affected pregnancy outcomes and fetal development, and that offspring showed impairments in anxiety as well as learning and memory, accompanied by impairments in hippocampal synaptic ultrastructure and synaptic plasticity. In addition, the IP3R-GRP75-VDAC1 apoptogenic pathway was also upregulated, and in vitro models showed that inhibition of this pathway alleviated neuronal apoptosis as well as synaptic plasticity damage. In conclusion, maternal Cy exposure during pregnancy can cause neurobehavioral abnormalities and synaptic damage in offspring, which may be related to neuronal apoptosis induced by activation of the IP3R-GRP75-VDAC1 pathway in the hippocampus of offspring. Our findings provide clues to understand the neurotoxicity mechanism of maternal Cy exposure to offspring during pregnancy.

Insights into the potential mechanism of liquid nitrogen spray freezing's influence on volatile compounds in surimi gels with different cross-linking degrees: Focus on oxidation, protein structure, intermolecular force and free amino acid alterations.

This study revealed the variations in odor characteristics and underlying mechanisms of different cross-linked surimi gels under liquid nitrogen (LN) spray freezing. The results demonstrated that LN spray freezing had an essential effect on the gels' odor. The odor changes in the -80 °C LN spray freezing group were closer to the control group, while -35 °C LN spray freezing treatment had the greatest impact on the aroma quality of gels. Freezing reduced gels' texture properties, intensified lipid and protein oxidation, altered protein conformation, increased surface hydrophobicity and hydrophobic interactions. These changes affected the gels' odor characteristics, leading to a reduction in fish aroma and an increase in fishy and oil odors after freezing. These tendencies were more pronounced at -35 °C LN spray freezing with lower cross-linking degrees, and reducing the freezing temperature to -80 °C and increasing the cross-linking degree to 62.99% mitigated the extent of deterioration in gel flavor quality.

Modulatory Effect of Low-Intensity Transcranial Ultrasound Stimulation on Behaviour and Neural Oscillation in Mouse Models of Alzheimer's Disease.

Transcranial ultrasound stimulation (TUS) is a noninvasive brain neuromodulation technique. The application of TUS for Alzheimer's disease (AD) therapy has not been widely studied. In this study, a long-term course (28 days) of TUS was used to stimulate the hippocampus of APP/PS1 mice. We examined the modulatory effect of TUS on behavior and neural oscillation in AD mice. We found that TUS can 1) improve the learning and memory abilities of AD mice; 2) reduce the phase-amplitude coupling of delta-epsilon, delta-gamma and theta-gamma frequency bands of local field potential, and increase the relative power of epsilon frequency bands in AD mice; 3) reduce the spike firing rate of interneurons and inhibit the phase-locked angle deflection between the theta frequency bands and the spikes of the two types of neurons that develops with the progression of the disease in AD mice. In summary, we demonstrate that TUS could effectively improve cognitive behavior and modulate neural oscillation with AD.

Associations of urinary metal concentrations with anemia: A cross-sectional study of Chinese community-dwelling elderly.

BACKGROUND: Anemia seriously affects the health and quality of life of the older adult population and may be influenced by various types of environmental metal exposure. Current studies on metals and anemia are mainly limited to single metals, and the association between polymetals and their mixtures and anemia remains unclear. METHODS: We determined 11 urinary metal concentrations and hemoglobin levels in 3781 participants. Binary logistic regression and restricted cubic spline (RCS) model were used to estimate the association of individual metals with anemia. We used Bayesian kernel machine regression (BKMR) and Quantile g-computation (Q-g) regression to assess the overall association between metal mixtures and anemia and identify the major contributing elements. Stratified analyses were used to explore the association of different metals with anemia in different populations. RESULTS: In a single-metal model, nine urinary metals significantly associated with anemia. RCS analysis further showed that the association of arsenic (As) and copper (Cu) with anemia was linear, while cobalt, molybdenum, thallium, and zinc were non-linear. The BKMR model revealed a significant positive association between the concentration of metal mixtures and anemia. Combined Q-g regression analysis suggested that metals such as Cu, As, and tellurium (Te) were positively associated with anemia, with Te as the most significant contributor. Stratified analyses showed that the association of different metals with anemia varied among people of different sexes, obesity levels, lifestyle habits, and blood pressure levels. CONCLUSIONS: Multiple metals are associated with anemia in the older adult population. A significant positive association was observed between metal mixture concentrations and anemia, with Te being the most important factor. The association between urinary metal concentrations and anemia is more sensitive in the non-hypertensive populations.

Effects of Cyfluthrin Exposure on Neurobehaviour, Hippocampal Tissue and Synaptic Plasticity in Wistar Rats.

This experiment was conducted to study the effects of Cyfluthrin (Cy) exposure on neurobehaviour, hippocampal tissue and synaptic plasticity in Wistar rats. First, it was found that high-dose Cy exposure could cause nerve injury, resulting in symptoms such as deficits in learning and memory ability, spatial exploration and autonomic motor function. Moreover, it was found that medium- and high-dose Cy exposure could cause an abnormal release of the neurotransmitter Glu. Second, brain tissue pathology showed that the middle and high doses of Cy caused tissue deformation, reduced the number of hippocampal puramidal cells, caused a disorder of these cells, decreased the number of Nissl bodies, and caused pyknosis of the hippocampal cell nuclear membrane and serious damage to organelles, indicating that exposure to these doses of Cy may cause hippocampal tissue damage in rats. Third, as the exposure dose increased, morphological changes in hippocampal synapses, including blurred synaptic spaces, a decreased number of synaptic vesicles and a decreased number of synapses, became more obvious. Moreover, the expression levels of the key synaptic proteins PSD-95 and SYP also decreased in a dose-dependent manner, indicating obvious synaptic damage. Finally, the study found that medium and high doses of Cy could upregulate the expression of A2AR in the hippocampus and that the expression levels of inflammatory factors and apoptosis-related proteins increased in a dose-dependent manner. Moreover, the expression of A2AR mRNA was correlated with neurobehavioural indicators and the levels of inflammatory factors, synaptic plasticity-related factors and apoptosis-related factors, suggesting that Cy may cause nerve damage in rats and that this effect is closely related to A2AR.

The directed acyclic graph helped identify confounders in the association between coronary heart disease and pesticide exposure among greenhouse vegetable farmers.

To explore the causal pathways associated with coronary heart disease (CHD) and pesticide exposure using a directed acyclic graph (DAG) analysis and to investigate the potential benefits of DAG by comparing it with logistic regression. This cross-sectional study enrolled 1368 participants from April 2015 to May 2017. Trained research investigators interviewed farmers using a self-administered questionnaire. Logistic regression and DAG models were used to identify the associations between CHD and chronic pesticide exposure. A total of 150 (11.0%) of the 1368 participants are characterized as having CHD. High pesticide exposure (odds ratio = 2.852, 95% confidence intervals: 1.951-4.171) is associated with CHD when compare with low pesticide exposure by both DAG and logistic analyses. After adjusting for the additional potential influence of factors identified by the DAG analysis, there is no significant association, such as the results in logistic regression: ethnicity, education level, settlement time, and mixed pesticide status. Specifically, age, meal frequency, and consumption of fresh fruit, according to the DAG analysis, are independent factors for CHD. High pesticide exposure is a risk factor for CHD as indicated by both DAG and logistic regression analyses. DAG can be a preferable improvement over traditional regression methods to identify sources of bias and causal inference in observational studies, especially for complex research questions.

Association between urinary neonicotinoid insecticide levels and dyslipidemia risk: A cross-sectional study in Chinese community-dwelling elderly.

Experimental evidence has demonstrated that neonicotinoids (NEOs) exposure can cause lipid accumulation and increased leptin levels. However, the relationship between NEOs exposure and dyslipidemia in humans remains unclear, and the interactive effects of NEOs and their characteristic metabolites on dyslipidemia remain unknown. We detected 14 NEOs and their metabolites in urine samples of 500 individuals (236 and 264 with and without dyslipidemia, respectively) randomly selected from the baseline of the Yinchuan community-dwelling elderly cohort (Ningxia, China). The NEOs and their metabolites were widely detected in urine (87.2-99.6 %) samples, and the median levels ranged within 0.06-0.55 µg/g creatinine. The positive associations and dose-dependent relationships of thiacloprid, imidacloprid-olefin, and imidacloprid-equivalent total with dyslipidemia were validated using restricted cubic spline analysis. Mixture models revealed a positive association between the NEOs mixture and dyslipidemia risk, with urine desnitro-imidacloprid ranked as the top contributor. The Bayesian Kernel Machine Regression models showed that the NEOs mixtures were associated with increased dyslipidemia when the chemical mixtures were ≥ 25th percentile compared to their medians, and desnitro-imidacloprid and imidacloprid-olefin were the major contributors to the combined effect. Given the widespread use of NEOs and the dyslipidemia pandemic, further investigations are urgently needed to confirm our findings and elucidate the underlying mechanisms.

Associations between changes of smartphone pedometer-assessed step counts and levels of obesity-related breast cancer biomarkers in non-cancer women: A population-based observational study.

While a higher level of physical activity (PA) is inversely associated with a higher breast cancer (BC) risk, the health benefits of daily steps on obesity-related BC biomarkers remain unclear. We aimed to understand the associations of changes in step counts with levels of five obesity-related BC biomarkers during a two-year follow-up. In total, 144 non-cancer women (47.96 ± 5.72) were observed on both 2019 and 2021. A structured questionnaire, daily steps and fasting blood samples were collected before (t0, 2019) and after (t1, 2021). Levels of biomarkers (IGF-binding proteins 3, adiponectin, soluble leptin receptor, C-reactive protein, and resistin) were assayed by ELISA. Participants were divided into persistent low steps, decreasing steps, increasing steps, and persistent high steps. Associations of categories on proposed biomarkers were estimated using linear regression models, with persistent low steps as reference. Associations between time-varying step counts with biomarkers were quantified using mixed linear models. Compared with persistent low steps, increasing steps is associated with a reduction in C-reactive protein level (ß=-0.74, 95%CI=-1.23--0.26, P-value = 2.98 × 10-3). An inverse association between time-varying step counts with C-reactive protein level was identified, consistent across different obesity types and baseline step level categories. No association with daily step counts was observed for other proteins.

Temporal relationships between BMI and obesity-related predictors of cardiometabolic and breast cancer risk in a longitudinal cohort.

Prospective inter-relationships among biomarkers were unexplored, which may provide mechanistic insights into diseases. We investigated the longitudinal associations of BMI change with trajectories of biomarkers related to cardiometabolic or breast cancer risk. A longitudinal study was conducted among 444 healthy women between 2019 to 2021. Cross­lagged path analysis was used to examine the temporal relationships among BMI, cardiometabolic risk score (CRS), and obesity­related proteins score (OPS) of breast cancer. Linear mixed-effect models were applied to investigate associations of time-varying BMI with biomarker-based risk score trajectories. Baseline BMI was associated with subsequent change of breast cancer predictors (P = 0.03), and baseline CRS were positively associated with OPS change (P < 0.001) but not vice versa. After fully adjustment of confounders, we found a 0.058 (95%CI = 0.009-0.107, P = 0.020) units increase of CRS and a 1.021 (95%CI = 0.041-1.995, P = 0.040) units increase of OPS as BMI increased 1 kg/m2 per year in postmenopausal women. OPS increased 0.784 (95%CI = 0.053-1.512, P = 0.035) units as CRS increased 1 unit per year. However, among premenopausal women, BMI only significantly affected CRS (ß = 0.057, 95%CI = 0.007 to 0.107, P = 0.025). No significant change of OPS with time-varying CRS was found. Higher increase rates of BMI were associated with worse trajectories of biomarker-based risk of cardiometabolic and breast cancer. The longitudinal impact of CRS on OPS is unidirectional. Recommendations such as weight control for the reduction of cardiometabolic risk factors may benefit breast cancer prevention, especially in postmenopausal women.

Slim the face or not: 3D change of facial soft and hard tissues after third molars extraction: a pilot study.

BACKGROUND: Whether slim the face or not after removed third molars is the concern of some orthodontic treatment candidates. The aim of this article is to explore the volume changes of facial soft and hard tissues after third molars extraction, as well as develop a reproducible clinical protocol to precisely assess facial soft tissue volume change. METHODS: A non-randomized, non-blind, self-controlled pilot study was conducted. 24 adults aged 18-30 had ipsilateral third molars extracted. The body weight change was controlled within 2 kg. Structured light scans were taken under a standardized procedure pre-extraction (T0), three (T1), and six (T2) months post-extraction; CBCTs were taken at T0 and T2. The projection method was proposed to measure the soft tissue volume (STV) and the soft tissue volume change (STVC) by the Geomagic software. The hard tissue volume change (HTVC) was measured in the Dragonfly software. RESULTS: The final sample size is 23, including 5 males (age 26.6 ± 2.5 years) and 18 females (age 27.3 ± 2.5 years). The HTVC was - 2.33 ± 0.46ml on the extraction side. On the extraction side, the STV decreased by 1.396 (95% CI: 0.323-2.470) ml (P < 0.05) at T1, and increased by 1.753 (95% CI: -0.01-3.507) ml (P = 0.05) at T2. T2 and T0 had no difference (P > 0.05). The inter and intra-raters ICC of the projection method was 0.959 and 0.974. There was no correlation between the STVC and HTVC (P > 0.05). CONCLUSIONS: After ipsilateral wisdom teeth extraction, the volume of hard tissue on the extraction side reduces, and the volume of facial soft tissue does not change evidently. However, further research with large sample size is still needed. The STV measurement has excellent repeatability. It can be extended to other interested areas, including forehead, nose, paranasal, upper lip, lower lip and chin, which is meaningful in the field of orthodontics and orthopedics. TRIAL REGISTRATION: ChiCTR, ChiCTR1800018305 (11/09/2018), http://www.chictr.org.cn/showproj.aspx?proj=28868 .

Age estimation based on 3D pulp segmentation of first molars from CBCT images using U-Net.

OBJECTIVE: To train a U-Net model to segment the intact pulp cavity of first molars and establish a reliable mathematical model for age estimation. METHODS: We trained a U-Net model by 20 sets of cone-beam CT images and this model was able to segment the intact pulp cavity of first molars. Utilizing this model, 239 maxillary first molars and 234 mandibular first molars from 142 males and 135 females aged 15-69 years old were segmented and the intact pulp cavity volumes were calculated, followed by logarithmic regression analysis to establish the mathematical model with age as the dependent variable and pulp cavity volume as the independent variable. Another 256 first molars were collected to estimate ages with the established model. Mean absolute error and root mean square error between the actual and the estimated ages were used to assess the precision and accuracy of the model. RESULTS: The dice similarity coefficient of the U-Net model was 95.6%. The established age estimation model was [Formula: see text] (V is the intact pulp cavity volume of the first molars). The coefficient of determination (R2), mean absolute error and root mean square error were 0.662, 6.72 years, and 8.26 years, respectively. CONCLUSION: The trained U-Net model can accurately segment pulp cavity of the first molars from three-dimensional cone-beam CT images. The segmented pulp cavity volumes could be used to estimate the human ages with reasonable precision and accuracy.

Parameterized Gompertz-Guided Morphological AutoEncoder for Predicting Pulmonary Nodule Growth.

The growth rate of pulmonary nodules is a critical clue to the cancerous diagnosis. It is essential to monitor their dynamic progressions during pulmonary nodule management. To facilitate the prosperity of research on nodule growth prediction, we organized and published a temporal dataset called NLSTt with consecutive computed tomography (CT) scans. Based on the self-built dataset, we develop a visual learner to predict the growth for the following CT scan qualitatively and further propose a model to predict the growth rate of pulmonary nodules quantitatively, so that better diagnosis can be achieved with the help of our predicted results. To this end, in this work, we propose a parameterized Gempertz-guided morphological autoencoder (GM-AE) to generate any future-time-span high-quality visual appearances of pulmonary nodules from the baseline CT scan. Specifically, we parameterize a popular mathematical model for tumor growth kinetics, Gompertz, to predict future masses and volumes of pulmonary nodules. Then, we exploit the expected growth rate on the mass and volume to guide decoders generating future shape and texture of pulmonary nodules. We introduce two branches in an autoencoder to encourage shape-aware and textural-aware representation learning and integrate the generated shape into the textural-aware branch to simulate the future morphology of pulmonary nodules. We conduct extensive experiments on the self-built NLSTt dataset to demonstrate the superiority of our GM-AE to its competitive counterparts. Experiment results also reveal the learnable Gompertz function enjoys promising descriptive power in accounting for inter-subject variability of the growth rate for pulmonary nodules. Besides, we evaluate our GM-AE model on an in-house dataset to validate its generalizability and practicality. We make its code publicly available along with the published NLSTt dataset.

Atypical Sweet syndrome: skin sinus tracts in an acutely febrile patient after lymphoma treatment: a case report.

Sweet syndrome (SS) is an uncommon inflammatory disease that involves painful skin, edematous, red papules, plaques, or nodules often accompanied by fever and leukocytosis. SS has three subtypes, including classical, malignant-tumor associated, and drug-induced SS (DISS). Patients with DISS have clear histories of recent drug exposure. The incidence of SS is high in hematological malignancy but rare in lymphomas. Glucocorticoid treatment is the recommended treatment for all subtypes of SS. This case study describes a male patient who had a history of sALCL(Systemic anaplastic large cell lymphoma) and was treated with multiple cycles of monoclonal-antibody (mAb) therapy. They also received the G-CSF injection at the site where skin lesions later developed. They met the diagnosis criteria for DISS, which was considered to be caused by the G-CSF injection. In addition, BV(Brentuximab vedotin) administration might predispose them to DISS. This case illustrates the first reported SS during the lymphoma treatment, with rare clinical presentations of local crater-like suppurative skin lesions. This case expands the available literature on SS and hematologic neoplasms and reminds clinicians to promptly recognize and diagnose SS to minimize patient morbidity and long-term sequelae.

Associations between multiple urinary metals and the risk of hypertension in community-dwelling older adults.

Although metal exposure has been associated with hypertension, the conclusions remain controversial, and studies investigating the predictive effect of multiple metals on hypertension are limited. In this study, we aimed to evaluate the nonlinear dose-response relationship between a single urinary metal and the risk of hypertension, and to assess the predictive effect of multiple urinary metals on hypertension. Of the Yinchuan community-dwelling elderly cohort launched in 2020, 3,733 participants (803 with hypertension and 2,930 without hypertension) were analysed in this study, and the concentrations of 13 metal elements in urine were measured. We found that urinary vanadium (odds ratio (OR): 1.16, 95% confidence interval [CI]: 1.08-1.25), molybdenum (OR: 1.08, 95% CI: 1.01-1.16), and tellurium (OR: 1.14, 95% CI: 1.06-1.22) were associated with higher risk of hypertension, whereas iron (OR: 0.92, 95% CI: 0.85-0.98) and strontium (0.92, 95% CI: 0.85-0.99) were significantly associated with lower risk of hypertension. Restricted cubic splines analysis was conducted in patients with iron concentrations of ≥ 15.48 µg/g and ≤ 399.41 µg/g and a strontium concentration of ≤ 69.41 µg/g, results showed that the risk of hypertension decreased gradually as the urinary concentrations of these metals increased. With an increase in the vanadium concentration in urine, the risk of hypertension gradually increased. In patients with a molybdenum concentration of ≥ 56.82 µg/g and a tellurium concentration of ≥ 21.98 µg/g, the risk of hypertension gradually decreased as the urinary concentrations of these metals increased. Predictive scores based on the 13 metallic elements were significantly associated with a higher risk of hypertension (OR: 1.34 (95% CI: 1.25-1.45). After additionally including urinary metal concentrations as a parameter variable in the traditional hypertension risk assessment model, integrated discrimination and net reclassification increased by 8.00% (P < 0.001) and 2.41% (P < 0.001), respectively. Urinary vanadium, Mo, and Te concentrations were associated with a higher risk of hypertension, while iron and strontium concentrations were associated with a lower risk of hypertension. Multiple urinary metal concentrations can significantly improve the predictive ability of traditional hypertension risk-assessment models.

Structure of the priming arabinosyltransferase AftA required for AG biosynthesis of Mycobacterium tuberculosis.

Arabinogalactan (AG) is an essential cell wall component in mycobacterial species, including the deadly human pathogen Mycobacterium tuberculosis. It plays a pivotal role in forming the rigid mycolyl-AG-peptidoglycan core for in vitro growth. AftA is a membrane-bound arabinosyltransferase and a key enzyme involved in AG biosynthesis which bridges the assembly of the arabinan chain to the galactan chain. It is known that AftA catalyzes the transfer of the first arabinofuranosyl residue from the donor decaprenyl-monophosphoryl-arabinose to the mature galactan chain (i.e., priming); however, the priming mechanism remains elusive. Herein, we report the cryo-EM structure of Mtb AftA. The detergent-embedded AftA assembles as a dimer with an interface maintained by both the transmembrane domain (TMD) and the soluble C-terminal domain (CTD) in the periplasm. The structure shows a conserved glycosyltransferase-C fold and two cavities converging at the active site. A metal ion participates in the interaction of TMD and CTD of each AftA molecule. Structural analyses combined with functional mutagenesis suggests a priming mechanism catalyzed by AftA in Mtb AG biosynthesis. Our data further provide a unique perspective into anti-TB drug discovery.

The Role of G3BP1 Gene Mediates P38 MAPK/JNK Pathway in Testicular Spermatogenic Dysfunction Caused by Cyfluthrin.

In recent years, male infertility has received global attention and seriously affected the quality of human fertility, and pyrethroids (type II pyrethroids), as recognized environmental endocrine disruptors, may threaten male reproductive health. Therefore, in this study, we established an in vivo model for the development of testicular and germ cell toxicity induced by cyfluthrin and explored the role and mechanism of the G3BP1 gene-mediated P38 MAPK/JNK pathway in testicular and germ cell damage caused by cyfluthrin to find early and sensitive indicators and new therapeutic targets for the development of testicular damage. Firstly, 40 male Wistar rats (about 260 g) were divided into a control group (corn oil), low dose group (6.25 mg/kg), middle dose group (12.5 mg/kg) and high dose group (25 mg/kg). The rats were anesthetized and executed after 28 days of poisoning on alternate days. Then, HE staining, transmission electron microscopy, ELISA, q-PCR, Western blot, immunohistochemistry, double-immunofluorescence and TUNEL were used to observe the pathology, androgen levels, oxidative damage and altered expression of the key factors of the G3BP1 and MAPK pathways in rat testes. The results showed that, compared with the control group, the testicular tissue and spermatocytes were superficially damaged with an increasing dose of cyfluthrin; furthermore, it could interfere with the normal secretion of the hypothalamic-pituitary-gonadal axis (serum GnRH, FSH, T and LH levels) and cause hypergonadal dysfunction. A dose-dependent increase in MDA and a dose-dependent decrease in T-AOC indicated that the oxidative-antioxidative homeostatic balance was disrupted. The Western blot and qPCR analysis revealed that G3BP1, p-JNK1/2/3, P38 MAPK, p-ERK, COX1 and COX4 proteins and mRNA expression were decreased, and p-JNK1/2/3, p-P38MAPK, caspase 3/8/9 proteins and mRNA expression were significantly increased. The double-immunofluorescence and immunohistochemistry results showed that the protein expression of G3BP1 decreased with an increasing dose of staining, while the expression of JNK1/2/3 and P38 MAPK were increased significantly. The positive expressions of G3BP1 were mainly located in the testicular germinal epithelium and germ cell layer, and the positive expressions of JNK1/2/3 were mainly located in the testicular germinal epithelium and sperm cells, while the positive expressions of P38 MAPK were located in all levels of the germ cells and spermatozoa. Our results demonstrated that exposure to cyfluthrin caused testicular and spermatocyte damage in rats, which could cause pathomorphology, altered androgen levels and a decreased antioxidant capacity. When the intracellular antioxidant capacity was impaired, G3BP1 expression and activity were inhibited, causing activation of the P38 MAPK/JNK pathway and activation of the intracellular apoptotic pathway, which, in turn, led to germ cell apoptosis.

Association between urinary metal concentrations and abnormal estimated glomerular filtration rate in Chinese community-dwelling elderly: Exploring the mediating effect of triglycerides.

BACKGROUND: Environmental metal exposure is associated with elevated triglycerides (TG) and the development of chronic kidney disease (CKD). However, the relationship between metal exposure and glomerular filtration rate (GFR) remains uncertain, and the mediating effect of TG between the two is unclear. METHODS: This study measured the concentrations of 14 metals in urine samples from 3752 elderly people in the community. The most relevant metals were screened by least absolute shrinkage and selection operator (LASSO) regression. The relationship between combined exposure to multiple metals and abnormal estimated glomerular filtration rate (eGFR) was explored using multivariate logistic regression analysis and Bayesian kernel machine regression (BKMR) analysis. Generalized linear regression models and the Karlson-Holm-Breen (KHB) method were used to assess the mediating effects of TG. RESULTS: In the single-metal model, calcium (Ca), iron (Fe), selenium (Se), strontium (Sr), and thallium (Tl) showed significant negative correlations with the prevalence of abnormal eGFR (all P < 0.05). In the multi-metals model, Ca, Se, and Tl continued to show significant negative correlations, while vanadium (V) and zinc (Zn) showed significant positive correlations with abnormal eGFR (all P < 0.05). The BKMR model showed a negative joint effect of the mixture of Ca, V, Zn, Se, and Tl on the prevalence of abnormal eGFR. The generalized linear regression model showed a significant positive correlation between the concentrations of Ca (ß = 0.07), Zn (ß = 0.07), Se (ß = 0.09), and TG levels (all P < 0.05). In the mediation analysis, TG masked a 4.30% and 5.21% correlation between Ca and Se and the prevalence of eGFR abnormalities, respectively. CONCLUSIONS: Urinary concentration of multiple metals is significantly associated with eGFR abnormalities, and Ca, and Se may be among the potential protective factors. TG masked some of the protective effects of Ca and Se.