X-ray-activated polymerization expanding the frontiers of deep-tissue hydrogel formation.

Photo-crosslinking polymerization stands as a fundamental pillar in the domains of chemistry, biology, and medicine. Yet, prevailing strategies heavily rely on ultraviolet/visible (UV/Vis) light to elicit in situ crosslinking. The inherent perils associated with UV radiation, namely the potential for DNA damage, coupled with the limited depth of tissue penetration exhibited by UV/Vis light, severely restrict the scope of photo-crosslinking within living organisms. Although near-infrared light has been explored as an external excitation source, enabling partial mitigation of these constraints, its penetration depth remains insufficient, particularly within bone tissues. In this study, we introduce an approach employing X-ray activation for deep-tissue hydrogel formation, surpassing all previous boundaries. Our approach harnesses a low-dose X-ray-activated persistent luminescent phosphor, triggering on demand in situ photo-crosslinking reactions and enabling the formation of hydrogels in male rats. A breakthrough of our method lies in its capability to penetrate deep even within thick bovine bone, demonstrating unmatched potential for bone penetration. By extending the reach of hydrogel formation within such formidable depths, our study represents an advancement in the field. This application of X-ray-activated polymerization enables precise and safe deep-tissue photo-crosslinking hydrogel formation, with profound implications for a multitude of disciplines.

The burden and management competency of cardiomyopathies in China: a nationwide survey study.

Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. Findings: The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. Interpretation: The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

REV-ERBα negatively regulates NLRP6 transcription and reduces the severity of Salmonella infection in mice.

Non-typhoidal Salmonella infection is among the most frequent foodborne diseases threatening human health worldwide. The host circadian clock orchestrates daily rhythms to adapt to environmental changes, including coordinating immune function in response to potential infections. However, the molecular mechanisms underlying the interplay between the circadian clock and the immune system in modulating infection processes are incompletely understood. Here, we demonstrate that NLRP6, a novel nucleotide-oligomerization domain (NOD)-like receptor (NLR) family member highly expressed in the intestine, is closely associated with the differential day-night response to Salmonella infection. The core clock component REV-ERBα negatively regulates NLRP6 transcription, leading to the rhythmic expression of NLRP6 and the secretion of IL-18 in intestinal epithelial cells, playing a crucial role in mediating the differential day-night response to Salmonella infection. Activating REV-ERBα with agonist SR9009 in wild-type mice attenuated the severity of infection by decreasing the NLRP6 level in intestinal epithelial cells. Our findings provide new insights into the association between the host circadian clock and the immune response to enteric infections by revealing the regulation of Salmonella infection via the inhibitory effect of REV-ERBα on NLRP6 transcription. Targeting REV-ERBα to modulate NLRP6 activation may be a potential therapeutic strategy for bacterial infections.

Rheological, thermal, and in vitro starch digestibility properties of oat starch-lipid complexes.

The influence of oat lipids on the structural, thermal, rheological, and in vitro digestibility properties of oat starch under heat processing conditions was investigated. X-ray diffraction, fourier infrared spectroscopy, and differential scanning calorimetry revealed the formation of a V-shaped crystal structure between starch and lipid, resulting in enhanced orderliness and enthalpy. Oat lipids decreased the final viscosity and gel strength of oat starch while weakening the trend towards gel network formation. Additionally, oat lipids exhibited enhanced resistance to starch hydrolase, leading to elevated contents of slowly digestible starch and resistant starch. Consequently, this leads to an augmentation in the rate constants for the rapid digestion fraction (k1) and the slow digestion fraction (k2). When the lipid content reached 7.50 %, a significant increase of 42.20 % was observed in the maximum digestibility of slow digestion fraction (C∞2), while a notable decrease of 44.06 % was noted in the maximum digestibility of rapid digestion fraction (C∞1). The correlation analysis revealed that lipid content, final viscosity, and enthalpy exerted significant influences on in vitro starch digestion. These results demonstrate the substantial impact of lipid content on oat starch structure, subsequently affecting its thermal, rheological, and digestive properties.

A randomized, double-blind, placebo-controlled, phase IIa, clinical study on investigating the efficacy and safety of SPH3127 tablet in patients with essential hypertension.

Around 70% of patients diagnosed with hypertension exhibit increased levels of renin. SPH3127, an inventive renin inhibitor, has shown favorable tolerability and sustained pharmacodynamic inhibitory impact on plasma renin activity (PRA) during previous phase I trials. This phase II study was conducted to investigate the efficacy and safety of SPH3127 in patients with essential hypertension. This study was conducted in patients with mild to moderate essential hypertension, utilizing a randomized, double-blind, placebo-controlled design. The patients were administered either tablet of SPH3127 at doses of 50 mg, 100 mg, or 200 mg, or a placebo. A total of 122 patients were included in the study, with 121 patients included in the full analysis set. Among these patients, there were 30 individuals in each subgroup receiving different dosage regimens of SPH3127, and 31 patients in the placebo group. The reductions in mean sitting diastolic blood pressure (msDBP) after 8 weeks compared to baseline were 5.7 ± 9.5, 8.6 ± 8.8, and 3.8 ± 10.6 mmHg in the SPH3127 50-, 100-, and 200 mg groups, respectively. In the placebo group, the reduction was 3.1 ± 8.4 mmHg. The corresponding reductions in mean sitting systolic blood pressure (msSBP) were 11.8 ± 13.0, 13.8 ± 11.2, 11.1 ± 13.1, and 7.7 ± 9.7 mmHg in each respective group. SPH3127 is a promising drug for the treatment of patients with essential hypertension. The recommended dosage is 100 mg daily.Clinical trial registration: This study was registered in ClinicalTrials.gov (NCT03756103).

A reinforcement learning enhanced pseudo-inverse approach to self-collision avoidance of redundant robots.

Introduction: Redundant robots offer greater flexibility compared to non-redundant ones but are susceptible to increased collision risks when the end-effector approaches the robot's own links. Redundant degrees of freedom (DoFs) present an opportunity for collision avoidance; however, selecting an appropriate inverse kinematics (IK) solution remains challenging due to the infinite possible solutions. Methods: This study proposes a reinforcement learning (RL) enhanced pseudo-inverse approach to address self-collision avoidance in redundant robots. The RL agent is integrated into the redundancy resolution process of a pseudo-inverse method to determine a suitable IK solution for avoiding self-collisions during task execution. Additionally, an improved replay buffer is implemented to enhance the performance of the RL algorithm. Results: Simulations and experiments validate the effectiveness of the proposed method in reducing the risk of self-collision in redundant robots. Conclusion: The RL enhanced pseudo-inverse approach presented in this study demonstrates promising results in mitigating self-collision risks in redundant robots, highlighting its potential for enhancing safety and performance in robotic systems.

A Noncentrosymmetric Metal-Free Borophosphate: Achieving a Large Birefringence and Excellent Stability by Covalent-Linkage.

Organic-inorganic hybrid linear and nonlinear optical (NLO) materials have received increasingly wide spread attention in recent years. Herein, the first hybrid noncentrosymmetric (NCS) borophosphate, (C5H6N)2B2O(HPO4)2 (4PBP), is rationally designed and synthesized by a covalent-linkage strategy. 4-pyridyl-boronic acid (4 PB) is considered as a bifunctional unit, which may effectively improve the optical properties and stability of the resultant material. On the one hand, 4 PB units are covalently linked with PO3(OH) groups via strong B-O-P connections, which significantly enhances the thermal stability of 4PBP (decomposition at 321, vs lower 200 °C of most of hybrid materials). On the other hand, the planar π-conjugated C5H6N units and their uniform layered arrangements represent large structural anisotropy and hyperpolarizability, achieving the largest birefringence (0.156 @ 546 nm) in the reported borophosphates and a second-harmonic generation response (0.7 × KDP). 4PBP also exhibits a wide transparency range (0.27-1.50 µm). This work not only provides a promising birefringent material, but also offers a practical covalent-attachment strategy for the rational design of new high-performance optical materials.

Toxic responses of environmental concentrations of bifenthrin in larval freshwater snail Bellamya aeruginosa.

Bifenthrin (BF) is ubiquitous in aquatic environments, and studies have indicated that environmental concentrations of BF could cause neurotoxicity and oxidative damage in fish and decrease the abundance of aquatic insects. However, little information is available on the toxicity of BF in freshwater benthic mollusks. Bellamya aeruginosa (B. aeruginosa) is a key benthic fauna species in aquatic ecosystems, and has extremely high economic and ecological values. In this study, larval B. aeruginosa within 24 h of birth were exposed to 0, 30 or 300 ng/L of BF for 30 days, and then the toxic effects from molecular to individual levels were comprehensively evaluated in all the three treatment groups. It was found that BF at 300 ng/L caused the mortality of snails. Furthermore, BF affected snail behaviors, evidenced by reduced crawling distance and crawling speed. The hepatopancreas of snails in the two BF exposure groups showed significant pathological changes, including increase in the number of yellow granules and occurrence of hemocyte infiltration, epithelial cell thinning, and necrosis. The levels of ROS and MDA were significantly increased after exposure to 300 ng/L BF, and the activities of two antioxidant enzymes SOD and CAT were increased significantly. GSH content decreased significantly after BF exposure, indicating the occurrence of oxidative damage in snails. Transcriptomic results showed that differentially expressed genes (DEGs) were significantly enriched in pathways related to metabolism and neurotoxicity (e.g., oxidative phosphorylation and Parkinson disease), and these results were consistent with those in individual and biochemical levels above. The study indicates that environmental concentration of BF results in decreased survival rates, sluggish behavior, histopathological lesions, oxidative damage, and transcriptomic changes in the larvae of B. aeruginosa. Thus, exposure of larval snails to BF in the wild at concentrations similar to those used in this study might have adverse consequences at the population level. These findings provide a theoretical basis for further assessing the ecological risk of BF to aquatic gastropods.

Gut microbiota: the indispensable player in neurodegenerative diseases.

As one of the most urgent social and health problems in the world, neurodegenerative diseases have always been attracted by researchers. However, the pathological mechanisms and therapeutic approaches are not achieved. In addition to the established roles of oxidative stress, inflammation and immune response, the changes of gut microbiota are also closely related to the pathogenesis of neurodegenerative diseases. Gut microbiota is the central player of gut- brain axis, the dynamic bidirectional communication pathway between gut microbiota and central nervous system, and emerging insights have confirmed its indispensability in the development of neurodegenerative diseases. In this review, we discussed the complex relationship between gut microbiota and the central nervous system from the perspective of gut-brain axis, reviewed the mechanism of microbiota on the modulation different neurodegenerative diseases and concluded how different dietary patterns affected neurodegenerative diseases via gut microbiota, and prospected the employment of gut microbiota in the therapeutic approach of those diseases. This article is protected by copyright. All rights reserved.

Mechanistic Insights into Dibasic Iminosugars as pH-Selective Pharmacological Chaperones to Stabilize Human α-Galactosidase.

The use of pharmacological chaperones (PCs) to stabilize specific enzymes and impart a therapeutic benefit is an emerging strategy in drug discovery. However, designing molecules that can bind optimally to their targets at physiological pH remains a major challenge. Our previous study found that dibasic polyhydroxylated pyrrolidine 5 exhibited superior pH-selective inhibitory activity and chaperoning activity for human α-galactosidase A (α-Gal A) compared with its monobasic parent molecule, 4. To further investigate the role of different C-2 moieties on the pH-selectivity and protecting effects of these compounds, we designed and synthesized a library of monobasic and dibasic iminosugars, screened them for α-Gal A-stabilizing activity using thermal shift and heat-induced denaturation assays, and characterized the mechanistic basis for this stabilization using X-ray crystallography and binding assays. We noted that the dibasic iminosugars 5 and 20 protect α-Gal A from denaturation and inactivation at lower concentrations than monobasic or other N-substituted derivatives; a finding attributed to the nitrogen on the C-2 methylene of 5 and 20, which forms the bifurcated salt bridges (BSBs) with two carboxyl residues, E203 and D231. Additionally, the formation of BSBs at pH 7.0 and the electrostatic repulsion between the vicinal ammonium cations of dibasic iminosugars at pH 4.5 are responsible for their pH-selective binding to α-Gal A. Moreover, compounds 5 and 20 demonstrated promising results in improving enzyme replacement therapy and exhibited significant chaperoning effects in Fabry cells. These findings suggest amino-iminosugars 5 and 20 as useful models to demonstrate how an additional exocyclic amino group can improve their pH-selectivity and protecting effects, providing new insights for the design of pH-selective PCs.

Effect of different buried depth on the disintegration characteristic of red-bed soft rock and the evolution model of disintegration breakage under cyclic drying-wetting.

The disintegration of red-bed soft rock exhibits a strong correlation with various geological disasters. However, the investigation into the evolutionary mechanisms underlying disintegration breakage has not yet received extensive exploration. In order to comprehensively examine the disintegration characteristics of red-bed soft rock, the slake durability tests were conducted to red-bed soft rocks of varying burial depths. Subsequently, an investigation was carried out to examine the disintegration characteristics and the evolution of disintegration parameters, including the coefficient of uniformity (Cu), coefficient of curvature (Cc), disintegration rate (DRE), disintegration ratio (Dr), and fractal dimension (D), throughout the disintegration process. Finally, employing the energy dissipation theory, an energy dissipation model was developed to predicate the disintegration process of samples at various burial depths. The findings demonstrate a decrease in the abundance of large particles and a concurrent increase in the abundance of small particles as the number of drying-wetting cycles increases. Furthermore, as the number of drying-wetting cycles increases, a significant alteration is observed in the content of particles larger than 10 mm, whereas the content of particles smaller than 10 mm undergoes only minor changes. The disintegration parameters, including the curvature coefficient, non-uniformity coefficient, disintegration rate, and fractal dimension, exhibit a positive correlation with the number of drying-wetting cycles. Conversely, the disintegration index demonstrates a decreasing trend with the increasing number of cycles. Nevertheless, as the burial depth increases, a notable trend emerges in the disintegration process, characterized by a gradual increase in the content of large particles alongside a progressive decrease in the content of small particles. Concurrently, the curvature coefficient, non-uniformity coefficient, disintegration rate, and fractal dimension exhibit a gradual decline, while the durability index experiences a gradual increase. In addition, based on the principle of energy dissipation, it is revealed that the surface energy increment of red-bed soft rock increases with the increase of the number of drying-wetting cycles, but decreases with the increase of burial depth. Ultimately, by leveraging the outcomes of energy dissipation analyses, a theoretical model is constructed to elucidate the correlation between surface energy and both the number of drying-wetting cycles and burial depth. This model serves as a theoretical reference for predicting the disintegration behavior of samples, offering valuable insights for future research endeavors.

Mechanical stress induced mitochondrial dysfunction in cardiovascular diseases: Novel mechanisms and therapeutic targets.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Others and our studies have shown that mechanical stresses (forces) including shear stress and cyclic stretch, occur in various pathological conditions, play significant roles in the development and progression of CVDs. Mitochondria regulate the physiological processes of cardiac and vascular cells mainly through adenosine triphosphate (ATP) production, calcium flux and redox control while promote cell death through electron transport complex (ETC) related cellular stress response. Mounting evidence reveal that mechanical stress-induced mitochondrial dysfunction plays a vital role in the pathogenesis of many CVDs including heart failure and atherosclerosis. This review summarized mitochondrial functions in cardiovascular system under physiological mechanical stress and mitochondrial dysfunction under pathological mechanical stress in CVDs (graphical abstract). The study of mitochondrial dysfunction under mechanical stress can further our understanding of the underlying mechanisms, identify potential therapeutic targets, and aid the development of novel treatments of CVDs.

Corrigendum: The utility of high-frequency 18 MHz ultrasonography for preoperative evaluation of acral melanoma thickness in Chinese patients.

[This corrects the article DOI: 10.3389/fonc.2023.1185389.].

Electro-optic 3D snapshot of a laser wakefield accelerated kilo-ampere electron bunch.

Laser wakefield acceleration, as an advanced accelerator concept, has attracted great attentions for its ultrahigh acceleration gradient and the capability to produce high brightness electron bunches. The three-dimensional (3D) density serves as an evaluation metric for the particle bunch quality and is intrinsically related to the applications of an accelerator. Despite its significance, this parameter has not been experimentally measured in the investigation of laser wakefield acceleration. We report on an electro-optic 3D snapshot of a laser wakefield electron bunch at a position outside the plasma. The 3D shape of the electron bunch was detected by simultaneously performing optical transition radiation imaging and electro-optic sampling. Detailed 3D structures to a few micrometer levels were reconstructed using a genetic algorithm. The electron bunch possessed a transverse size of less than 30 micrometers. The current profile shows a multi-peak structure. The main peak had a duration of < 10 fs and a peak current > 1 kA. The maximum electron 3D number density was ~ 9 × 1021 m -3. This research demonstrates a feasible way of 3D density monitoring on femtosecond kilo-ampere electron bunches, at any position of a beam transport line for relevant applications.

USP5 promotes tumorigenesis by activating Hedgehog/Gli1 signaling pathway in osteosarcoma.

Changes in protein ubiquitination have been linked to cancer. Deubiquitinating enzymes (DUBs) counteract E3 ligase activities and have emerged as promising targets for cancer treatment. Ubiquitin-specific peptidase 5 (USP5) is a member of the DUBs family and has been implicated in promoting tumorigenesis in numerous cancers. However, the clinical significance and biological function of USP5 in osteosarcoma (OS) remains unclear. Here, we found elevated USP5 expression in OS tissues compared with normal bone tissues. Furthermore, we observed significant associations of elevated USP5 levels with increased mortality and more malignant phenotypes in OS patients. Moreover, our results revealed that USP5 could facilitate metastasis and cell progression in OS by activating the hedgehog (Hh) signaling pathway using cultured cells and animal tumor models. Mechanistically, USP5 appeared to stabilize and deubiquitinate Gli1, a key mediator of the Hh signaling pathway. Additionally, the oncogenic effect of USP5 in OS was dependent on Gli1 stability. Our findings support the model where USP5 contributes to OS pathogenesis by activating the Hh/Gli1 signaling pathway, making USP5 a potential diagnostic and therapeutic target for OS.

Context-Based Meta-Reinforcement Learning with Bayesian Nonparametric Models.

Deep reinforcement learning agents usually need to collect a large number of interactions to solve a single task. In contrast, meta-reinforcement learning (meta-RL) aims to quickly adapt to new tasks using a small amount of experience by leveraging the knowledge from training on a set of similar tasks. State-of-the-art context-based meta-RL algorithms use the context to encode the task information and train a policy conditioned on the inferred latent task encoding. However, most recent works are limited to parametric tasks, where a handful of variables control the full variation in the task distribution, and also failed to work in non-stationary environments due to the few-shot adaptation setting. To address those limitations, we propose MEta-reinforcement Learning with Task Self-discovery (MELTS), which adaptively learns qualitatively different nonparametric tasks and adapts to new tasks in a zero-shot manner. We introduce a novel deep clustering framework (DPMM-VAE) based on an infinite mixture of Gaussians, which combines the Dirichlet process mixture model (DPMM) and the variational autoencoder (VAE), to simultaneously learn task representations and cluster the tasks in a self-adaptive way. Integrating DPMM-VAE into MELTS enables it to adaptively discover the multi-modal structure of the nonparametric task distribution, which previous methods using isotropic Gaussian random variables cannot model. In addition, we propose a zero-shot adaptation mechanism and a recurrence-based context encoding strategy to improve the data efficiency and make our algorithm applicable in non-stationary environments. On various continuous control tasks with both parametric and nonparametric variations, our algorithm produces a more structured and self-adaptive task latent space and also achieves superior sample efficiency and asymptotic performance compared with state-of-the-art meta-RL algorithms.

New-onset atrial fibrillation is a red flag to microvascular free tissue transfer failure in head and neck cancer patients.

Background Postoperative new-onset atrial fibrillation (AF) has been shown to be associated with increased surgical morbidity and mortality following cancer ablation surgery. However, evidence on new-onset AF's impact on surgical outcomes in head and neck cancer patients undergoing tumor ablation and microvascular free tissue transfer remains scarce. This study aims to evaluate the association between AF and surgical outcomes in these patients. Methods We enrolled head and neck cancer patients who underwent tumor ablation reconstructed with microvascular free tissue transfer from the National Health Insurance Research Database (NHIRD). Patients were grouped into (1) without AF, (2) new-onset AF, and (3) preexisting AF. The groups were matched by propensity score based on age, gender, cancer stage, and comorbidities. The primary outcome was postoperative complications, whereas all-cause mortality was the secondary outcome. Results Total 26,817 patients were included in this study. After matching, we identified 2,176 (79.24%) patients without AF, 285 (10.37%) with preexisting AF, and 285 (10.37%) with new-onset AF. Our results demonstrated that the free flap failure rate was twofold escalated in patients with new-onset AF (9.8%) compared to those without AF (5.4%) or preexisting AF (5.3%) (p = 0.01). However, we did not identify significant differences among other postoperative complications across groups. Additionally, we found that the risk of all-cause mortality was significantly elevated in patients with preexisting AF (p<0.001) compared to those without AF or new-onset AF. Conclusion Our study demonstrated that new-onset AF is associated with an increased risk of flap failure and could serve as a predictor. On the other hand, all-cause mortality in patients with preexisting AF was significantly elevated. Close postoperative monitoring in patients with new-onset and preexisting AF is crucial to identify any potential adverse effects.

Deciphering core microbiota in rhizosphere soil and roots of healthy and Rhizoctonia solani-infected potato plants from various locations.

Black scurf caused by Rhizoctonia solani severely affects potato production. Through amplification of V3-V4 and ITS1-5f variable regions of 16S and internal transcribed spacer (ITS) rRNA, the study was based on the location (Kunming, Qujing, and Zhaotong), plant components (rhizosphere soil and roots), and sample types (healthy and diseased) to assess the diversity of bacterial and fungal communities. We found plant components significantly influence microbial diversity, with rhizosphere soil being more diverse than roots, and the microbial community in the root is mainly derived from the rhizosphere soil. Moreover, the rhizosphere soil and roots of healthy potato plants exhibit greater microbial diversity compared to those of potato plants infected by Rhizoctonia solani. Bacterial phyla Actinobacteriota and Acidobacteriota were enriched in rhizosphere soil compared to that of roots, whereas Proteobacteria and Cyanobacteria showed the opposite trend. Fungal phylum Ascomycota was found in low relative abundance in rhizosphere soil than in roots, whereas Basidiomycota showed the opposite trend. Bacterial genera including Streptomyces, Lysobacter, Bacillus, Pseudomonas, Ensifer, Enterobacter, and the Rhizobium group (Allorhizobium, Neorhizobium, Pararhizobium, Rhizobium), along with fungal genera such as Aspergillus, Penicillium, Purpureocillium, and Gibberella moniliformis, have the potential ability of plant growth promotion and disease resistance. However, most fungal species and some bacterial species are pathogenic to potato and could provide a conducive environment for black scurf infection. Interaction within the bacterial network increased in healthy plants, contrasting with the trend in the fungal network. Our findings indicate that R. solani significantly alters potato plant microbial diversity, underscoring the complexity and potential interactions between bacterial and fungal communities for promoting potato plant health and resistance against black scurf.

The white matter characteristic of the genu of corpus callosum coupled with pain intensity and negative emotion scores in patients with trigeminal neuralgia: a multivariate analysis.

Background: Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder that not only causes intense pain but also affects the psychological health of patients. Since TN pain intensity and negative emotion may be grounded in our own pain experiences, they exhibit huge inter-individual differences. This study investigates the effect of inter-individual differences in pain intensity and negative emotion on brain structure in patients with TN and the possible pathophysiology mechanism underlying this disease. Methods: T1 weighted magnetic resonance imaging and diffusion tensor imaging scans were obtained in 46 patients with TN and 35 healthy controls. All patients with TN underwent pain-related and emotion-related questionnaires. Voxel-based morphometry and regional white matter diffusion property analysis were used to investigate whole brain grey and white matter quantitatively. Innovatively employing partial least squares correlation analysis to explore the relationship among pain intensity, negative emotion and brain microstructure in patients with TN. Results: Significant difference in white matter integrity were identified in patients with TN compared to the healthy controls group; The most correlation brain region in the partial least squares correlation analysis was the genus of the corpus callosum, which was negatively associated with both pain intensity and negative emotion. Conclusion: The genu of corpus callosum plays an important role in the cognition of pain perception, the generation and conduction of negative emotions in patients with TN. These findings may deepen our understanding of the pathophysiology of TN.

First comprehensive assessment of dietary chlorinated paraffins intake and exposure risk for the rural population of the Tibetan Plateau, China.

Knowledge regarding the occurrence of short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs) in foodstuffs and their dietary exposure risks for rural Tibetan residents remains largely unknown. Herein, we collected main foodstuffs (including highland barley, vegetables, Tibetan butter, mutton, and yak beef) across the rural Tibetan Plateau and characterized the CP profiles and concentrations. The highest SCCPs concentrations were detected in Tibetan butter (geometric mean (GM): 240.6 ng/g wet weight (ww)), followed by vegetables (59.4 ng/g ww), mutton (51.4 ng/g ww), highland barley (46.3 ng/g ww), and yak beef (31.7 ng/g ww). For MCCPs, the highest concentrations were also detected in Tibetan butter (319.5 ng/g ww), followed by mutton (181.9 ng/g ww), vegetables (127.0 ng/g ww), yak beef (71.2 ng/g ww), and highland barley (30.3 ng/g ww). The predominant congener profiles of SCCPs were C13Cl7-8 in mutton and yak beef, C10Cl7-8 in Tibetan butter, and C10-11Cl6-7 in highland barley and vegetables. The predominant congener profiles of MCCPs were C14Cl7-9 in all sample types. Combined with our previous results of free-range chicken eggs, the median estimated daily intakes (EDIs) of SCCPs and MCCPs via diet for Tibetan rural adults and children was estimated to be 728.8 and 1853.9 ng/kg bw/day and 2565.6 and 5952.8 ng/kg bw/day, respectively. In the worst scenario, MCCPs might induce potential health risks for rural Tibetan population. To our knowledge, this is the first systematic dietary exposure research of SCCPs and MCCPs in the remote rural areas.