Smart Response Biomaterials for Pain Management.

The intricate nature of pain classification and mechanism constantly affects the recovery of diseases and the well-being of patients. Key medical challenges persist in devising effective pain management strategies. Therefore, a comprehensive review of relevant methods and research advancements in pain management is conducted. This overview covers the main categorization of pain and its developmental mechanism, followed by a review of pertinent research and techniques for managing pain. These techniques include commonly prescribed medications, invasive procedures, and noninvasive physical therapy methods used in rehabilitation medicine. Additionally, for the first time, a systematic summary of the utilization of responsive biomaterials in pain management is provided, encompassing their response to physical stimuli such as ultrasound, magnetic fields, electric fields, light, and temperature, as well as changes in the physiological environment like reactive oxygen species (ROS) and pH. Even though the application of responsive biomaterials in pain management remains limited and at a fundamental level, recent years have seen the examination and debate of relevant research findings. These profound discussions aim to provide trends and directions for future research in pain management.

TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD.

Background/Aims: Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. Methods: The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). Results: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury of HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFD-induced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell-membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. Conclusions: The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

Inhibiting Dissolution of Active Sites in 80 °C Alkaline Water Electrolysis by Oxyanion Engineering.

Commercial alkaline water electrolysers typically operate at 80 °C to minimize energy consumption. However, NiFe-based catalysts, considered as one of the most promising candidates for anode, encounter the bottleneck of high solubility at such temperatures. Herein, we discover that the dissolution of NiFe layered double hydroxides (NiFe-LDH) during operation not only leads to degradation of anode itself, but also deactivates cathode for water splitting, resulting in decay of overall electrocatalytic performance. Aiming to suppress the dissolution, we employed oxyanions as inhibitors in electrolyte. The added phosphates to the electrolyte inhibit the loss of NiFe-LDH active sites at 400 mA cm-2 to 1/3 of the original amount, thus reducing the rate of performance decay by 25-fold. Furthermore, the usage of borates, sulfates, and carbonates yields similar results, demonstrating the reliability and universality of the active site dissolution inhibitor, and its role in elevated water electrolysis.

Electroencephalography Microstate Class D is a Brain Marker of Subjective Sleep Quality for College Students with High Habitual Sleep Efficiency.

Subjective sleep quality is an individual's subjective sleep feeling, and its effective evaluation is the premise of improving sleep quality. However, people with autism or mental disorders often experience difficulties in verbally expressing their subjective sleep quality. To solve the above problem, this study provides a non-verbal and convenient brain feature to assess subjective sleep quality. Reportedly, microstates are often used to characterize the patterns of functional brain activity in humans. The occurrence frequency of microstate class D is an important feature in the insomnia population. We therefore hypothesize that the occurrence frequency of microstate class D is a physiological indicator of subjective sleep quality. To test this hypothesis, we recruited college students from China as participants [N = 61, mean age = 20.84 years]. The Chinese version of the Pittsburgh Sleep Quality Index scale was used to measure subjective sleep quality and habitual sleep efficiency, and the state characteristics of the brain at this time were assessed using closed eyes resting-state brain microstate class D. The occurrence frequency of EEG microstate class D was positively associated with subjective sleep quality (r = 0.32, p < 0.05). Further analysis of the moderating effect showed that the occurrence frequency of microstate class D was significantly and positively correlated with subjective sleep quality in the high habitual sleep efficiency group. However, the relationship was not significant in the low sleep efficiency group (ßsimple = 0.63, p < 0.001). This study shows that the occurrence frequency of microstate class D is a physiological indicator of assessing subjective sleep quality levels in the high sleep efficiency group. This study provides brain features for assessing subjective sleep quality of people with autism and mental disorders who cannot effectively describe their subjective feelings.

A rare case of pulmonary artery embolism with choriocarcinoma: A case report and literature review.

Pulmonary embolism (PE) caused by malignant tumor is not uncommon, but pulmonary artery with choriocarcinoma is rare and difficult to timely diagnose and effectively treat. To the best of our knowledge, there are only 15 cases reported at present in the literature that present variable clinical characteristics and prognosis. In the current study reports a 21-year-old female with a history of chest pain and slight fever for 4 months who was treated as a case of pneumonia. Owing to the recurrence of the symptoms, a contrast-enhanced chest computer tomography scan was performed on the patient, which revealed complete occlusion of the right pulmonary artery. The patient was diagnosed to have pulmonary embolism (PE). However, no abnormalities were observed in D-dimer value, tumor antigen testing or ultrasonography. Positron emission tomography/computed tomography (PET/CT) was performed, which revealed the abnormal hypermetabolic lesion of the right pulmonary artery. Following the laboratory report of a significantly elevated human chorionic gonadotropin ß-subunit level combined with characteristic appearance of PET-CT, the diagnosis of primary pulmonary artery with choriocarcinoma was established based on guidelines of the European Society for Medical Oncology and the criteria formulated by the International Federation of Gynecology and Obstetrics. The patient underwent chemotherapy and responded well to the treatment. Although rare, choriocarcinoma should be considered for any fertile women who presents with a massive PE. These findings emphasize the importance of the early diagnosis and treatment of this disease.

The thalamic clustering coefficient moderates the vigor-sleep quality relationship.

Sleep disorders affect more than one-quarter of the world's population, resulting in reduced daytime productivity, impaired immune function, and an increased risk of cardiovascular disease. It is important to identify the physiological and psychological factors related to sleep for the prevention and treatment of sleep disorders. In this study, we correlated measurements of emotional state, sleep quality, and some brain neural activity parameters to better understand the brain and psychological factors related to sleep. Resting-state functional magnetic resonance imaging (rs-fMRI) of 116 healthy undergraduates were analyzed using graph theory to assess regional topological characteristics. Among these, the left thalamic cluster coefficient proved to be the ablest to reflect the characteristics of the sleep neural graph index. The Profile of Mood States (POMS) was used to measure vigor, and the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. The results showed that the left thalamic clustering coefficient was negatively correlated with sleep quality and vigor. Further, the left thalamic clustering coefficient moderated the relationship between vigor and sleep quality. When the left thalamic clustering coefficient was very low, there was a significant positive correlation between vigor and sleep quality. However, when the left thalamic clustering coefficient was high, the correlation between vigor and sleep quality became insignificant. The relationship between vigor and sleep quality is heterogeneous. Analyzing the function of the left thalamic neural network could help understand the variation in the relationship between vigor and sleep quality in different populations. Such observations may help in the development of personalized interventions for sleep disorders.

Correction: The thalamic clustering coefficient moderates the vigor-sleep quality relationship.

[This corrects the article DOI: 10.1007/s41105-023-00456-2.].

Notch/NICD/RBP-J signaling axis regulates M1 polarization of macrophages mediated by advanced glycation end products.

Advanced glycation end products (AGEs) aggregation and macrophages polarization are identified as the main factors contributing to bone diseases caused by aging or diabetes, such as senile or diabetic osteoporosis. Here, we aimed to elucidate the involvement and potential mechanism of AGEs in macrophages polarization and osteoclastogenesis. Firstly, AGEs-treated RAW264.7 macrophages were observed to up-regulate the release of nitric oxide (NO), the expression of M1-associated genes and the surface antigen marker CD86. The detection of osteoclast-related markers and TRAP staining revealed that the osteoclastogenic ability of M1 macrophages was markedly enhanced by AGEs. Further, AGEs were found to effectively activate the transduction of Notch signaling pathway and promote the nuclear translocation of NICD1. In addition, with the signals transduction of Notch pathway blocked by γ-secretase inhibitor DAPT and siRNA targeting silencing RBP-J, AGEs-induced M1 polarization was significantly mitigated. Collectively, we defined a critical role for AGEs in inducing M1 polarization and osteoclastogenesis of macrophages, and further identified Notch/NICD/RBP-J signaling axis as an essential mechanism regulating AGEs-mediated M1 polarization.

Cytotoxicity and apoptosis induced by enrofloxacin in loach fin cells in vitro.

The cytotoxic effect and cell death were studied in loach fin cells in vitro after enrofloxacin (ENR) exposure. The semi-lethal concentration of ENR for loach cells was calculated as 1296.2 ± 3.11 mol/L (about 512.5 mg/L). Loss of cell viability, increase in vacuoles, disappearance of microvilli, and apoptotic bodies were evident in cells exposed to 400, 800, and 1200 µmol/L ENR. Besides, dose-dependent inhibitory effects on SOD, CAT, Na+-K+-ATPase, and Ca2+-ATPase activities were also observed in loach cells exposed to ENR. Quantitative gene expression results showed that ENR induced caspase-3- and caspase-8-mediated apoptosis as well as caspase-activated DNase in loach cells. The findings also indicated a role of JNK pathway in ENR-induced apoptosis in loach cells. Transcriptome sequencing results showed 10,016 differentially expressed genes in ENR vs. control groups, which were all enriched in "Molecular Function" process in GO term. Furthermore, 6763 genes were enriched in 291 KEEG pathways, with most of them belonging to immune and material metabolic pathways. The large number of transcriptome data and pathways determined in this study provide a database foundation for the toxicity analysis of ENR in loach cells, which must be thoroughly examined to further investigate the cytotoxic mechanism of antibiotics in fish cells.

Efficiency moderates the relationship between sleep-onset insomnia and resting-state electroencephalogram microstate.

BACKGROUND: Overactivation of the salience network (SN) causes hyperarousal in insomnia patients and is associated with sleep-onset insomnia (SOI). Resting-state microstate 3 (RS-MS3) duration is closely related to SN overactivation. However, whether RS-MS3 duration is a biomarker for SOI has not yet been reported in the literature. In addition, SN activity is also associated with efficiency. However, it is not clear whether there are individual differences in the neural mechanisms of SOI in different efficiency groups. METHODS: Considering that RS-MS3 duration characterizes the stability and persistent activation of the SN in the resting state, the current study investigated the link between SOI measured by sleep latency of Pittsburg Sleep Quality Index (PSQI), efficiency measured by Kirton Adaption-Innovation Inventory (KAI), and RS-MS3 in a Chinese healthy (subclinical) student population, using electroencephalography (EEG) microstate analysis. RESULTS: We found that RS-MS3 duration was positively correlated with sleep latency and efficiency. The interaction between sleep latency and efficiency was significant. Simple slope analysis showed that high sleep latency was positively correlated with longer RS-MS3 duration in participants with higher efficiency scores. This correlation did not exist in participants with low efficiency scores. CONCLUSIONS: RS-MS3 duration may serve as a biomarker for SOI. There is heterogeneity in the relationship between SOI and RS-MS3 duration between individuals with high and low efficiency.

Erratum: Effect of local application of biphosphonates on improving peri-implant osseointegration in type-2 diabetic osteoporosis.

[This corrects the article on p. 5417 in vol. 11, PMID: 31632520.].

Hygromycin A derivatives isolated from Streptomyces sp. PC-22 in the rhizosphere soil of Pulsatilla chinensis.

On the basis of the one strain-many compounds (OSMAC) strategy, two new hygromycin A derivatives (3, 4), together with six known compounds were isolated from a medicinal plant inter rhizospheric Streptomyces in Pulsatilla chinensis. The structures of 3 and 4 were elucidated using NMR and HRESIMS analyses. A plausible biosynthetic pathway for these compounds was discussed. All the compounds were evaluated for their antimicrobial and cytotoxic activities. Compound 5 exhibited potent inhibitory activity against S. aureus and B. subtilis with the MICs of 16 and 8 µg ml-1, while 4 showed weak inhibitory activity against S. aureus.

Chlorogenic acid and Epicatechin: An efficient inhibitor of heterocyclic amines in charcoal roasted lamb meats.

There are few studies on controlling the formation of heterocyclic amines (HAs) by adding polyphenols to roasted lamb. The aim of this study was to assess the inhibitory effect of 0.025, 0.125, and 0.625 mmol of chlorogenic acid, epicatechin, rutin, quercetin and quinic acid on the formation of HAs in charcoal roasted lamb, respectively, by UHPLC-MS/MS. The results indicated that Harman, Norharman, PhIP, IQx and 8-MeIQx were detected, but both chlorogenic acid and epicatechin greatly inhibited the formation of IQx, 8-MeIQx, Norharman, Harman and PhIP, and epicatechin had better inhibitory effect than chlorogenic acid. PLSR-VID analysis suggested the key precursors of HAs formation in roasted lamb were glucose, ribose, fructose, isoleucine, valine, and lysine. In addition, this work also implied that the potential mechanism of inhibition of HAs formation by chlorogenic acid and epicatechin in roasted lamb might attribute to competitive chemical reactions between polyphenols and key precursors of HAs.

Mechanisms in Which Smoking Increases the Risk of COVID-19 Infection: A Narrative Review.

At present, COVID-19 continues to spread around the world. People are generally susceptible to SARS-CoV-2. The elderly, serious chronic underlying diseases, high-risk pregnancy, severe obesity and other factors are related to the progression of COVID-19 to severe, critical illness, and even death caused by deterioration of the disease. The relationship between smoking and COVID-19 seems to be controversial. The smoking rate of hospitalized COVID-19 patients is significantly lower than that of the general population. Therefore, smoking can reduce COVID-19 infection and protect the respiratory tract. Subsequently, many scholars have carried out research on this, thinking that this is a wrong and misleading conclusion. According to WHO, smoking is significantly related to the severity of COVID-19, which is one of the important risk factors for the deterioration and poor prognosis of COVID-19. This article reviews the mechanism of smoking increasing the risk of COVID-19 infection.

Dendrocrepidamine, a novel octahydroindolizine alkaloid from the roots of Dendrobium crepidatum.

A novel octahydroindolizine alkaloid, named dendrocrepidamine (1) with an unusual 18,19,19'-cyclopropanone-dendrocrepine skeleton, was isolated from the ethanol extract of the roots of Dendrobium crepidatum, along with six known compounds (2-7). The structure of 1 was elucidated through HR-ESIMS, NMR spectroscopic data and computational calculations. All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells with IC50 values in the range of 3.04-54.89 µM. In vivo, crepidatin (6) (80, 40 and 10 mg/kg) showed a significant protective effect against LPS-induced acute lung injury (ALI) in mice.

Effect of advanced glycation end products on autophagic ability in osteoblasts. / 晚期糖基化终末产物对成骨细胞自噬能力的影响.

OBJECTIVES: Excessive production of AGEs in diabetic patients will affect the normal function of osteoblasts, and this process may be related to autophagy of osteoblasts. This study aims to explore the effect of advanced glycation end products (AGEs) on autophagic activity during osteogenic differentiation in rat bone marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs were isolated and cultured in vitro, treated with different concentrations (0, 50, 100, 200, and 400 mg/L) of AGEs for different time (3, 6, 12, 24, 48, and 72 h). The proliferation activity was detected by CCK-8 method. The mRNA and protein expression levels of Beclin1 and LC3 in cells were detected by real-time PCR and Western blotting, respectively.The autophagic vacuoles were observed under the transmission electron microscope. The cells were treated with autophagy promoter rapamycin or autophagy inhibitor 3MA. After 7 days of osteogenic induction, we performed alkaline phosphatase (ALP) staining and real-time PCR to detect the mRNA expression levels of osteogenesis-related genes. RESULTS: In the low-concentration groups, the proliferation activity in BMSCs was increased (P<0.01), the mRNA and protein expressions of autophagy-related genes LC3 and Beclin1 were increased (both P<0.01). The number of autophagosome also was increased. In the high-concentration groups, the results were just the opposite. In the low-concentration groups, the ALP staining was deeper than that of the 0 mg/L AGEs group, and the mRNA expressions of the osteogenic related genes were increased (P<0.01). But the results were reversed in the presence of autophagy inhibitor 3MA. In the high-concentration groups, the ALP staining was lighter than that of the 0 mg/L AGEs group, and the mRNA expressions of the osteogenic related genes were decreased (P<0.01). After the addition of the autophagy promoter rapamycin, the results were reversed. CONCLUSIONS: Low concentration of AGEs can enhance the proliferative activity of BMSCs and promote osteogenic differentiation by accelerating autophagy. High concentration of AGEs can suppress the proliferation of BMSCs and inhibit osteogenic differentiation by reducing autophagy.

Exploring the Relationship Between Trait Mindfulness and Interpersonal Sensitivity for Chinese College Students: The Mediating Role of Negative Emotions and Moderating Role of Effectiveness/Authenticity.

Background: Interpersonal sensitivity is a prominent mental health problem facing college students today. Trait mindfulness is a potential positive factor that may influence interpersonal relationships. However, the precise relationship between trait mindfulness and interpersonal sensitivity remains elusive, which limits the optimization and further application of mindfulness-based intervention schemes targeting interpersonal sensitivity. This study aimed to explore (a) whether negative emotions mediate the relationship between trait mindfulness and interpersonal sensitivity and (b) whether the relationship among trait mindfulness, negative emotions, and interpersonal sensitivity is moderated by effectiveness/authenticity. We hypothesize that (a) negative emotions mediate the relationship between trait mindfulness and interpersonal sensitivity, and (b) effectiveness/authenticity moderates the indirect association between trait mindfulness and interpersonal sensitivity through negative emotions. Methods: One thousand four hundred nineteen Chinese college students (1,023 females, 396 males), aged from 17 to 23 (SD = 0.86, mean = 18.38), participated in this study. Their trait mindfulness, negative emotions, the effectiveness/authenticity, and interpersonal sensitivity were measured using well-validated self-report questionnaires. Results: Correlational analyses indicated that both trait mindfulness and effectiveness/authenticity were significantly and negatively associated with interpersonal sensitivity. Mediation analyses uncovered a partial mediating role of negative emotions in the relationship between trait mindfulness and interpersonal sensitivity. Moderated mediation analyses showed that in college students with high effectiveness/authenticity, the relationship between trait mindfulness and negative emotions was stronger, whereas the relationship between negative emotions and interpersonal sensitivity was weaker. Conclusion: Negative emotion is a mediator of the relationship between trait mindfulness and interpersonal sensitivity, which in turn is moderated by effectiveness/authenticity. These findings suggest a potential mechanism through which trait mindfulness influences interpersonal sensitivity. Mindfulness-based interventions have the potential to decrease interpersonal sensitivity and offer a basis for predicting individual differences in response to mindfulness-based interventions among individuals.

Immune checkpoint inhibitor-induced myocarditis in lung cancer patients: a case report of sintilimab-induced myocarditis and a review of the literature.

Since its initial approval by the United States Food and Drug Administration (FDA) in 2014, the indications for the use of the immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients has increased. However, to date, there has no report on immune myocarditis caused by the ICI sintilimab. In addition, there has been no literature review on ICI-induced myocarditis in lung cancer patients. This is a case report of an elderly male patient who presented with a productive cough and progressive dysphagia for 3 days. The symptoms started on day 6 after the third cycle of sintilimab treatment for his lung carcinoma. In accordance with his clinical manifestations of progressive dysphagia, a previous history of lung cancer, abnormal electrocardiograph, significantly increased serum myocardial enzyme levels, and normal coronary angiography results, sintilimab-induced myocarditis was diagnosed. Methylprednisolone (80-40 mg) was used to inhibit the immune injury and the patient was safely discharged on the 13th day following admission. Since ICI-induced myocarditis is rare and fatal, we summarized the characteristics of 20 cases of the disease in lung cancer patients to highlight to oncologists, respiratory experts, and cardiologists the serious side effects of the drug when they encounter lung cancer patients using ICIs. Like most ICIs, sintilimab induces severe immune myocarditis and requires corticosteroids therapy, and this should be recognized by doctors in multiple departments.

Effects of C/N ratio and dissolved oxygen on aerobic denitrification process: A mathematical modeling study.

COD to ammonium nitrogen (C/N) ratio and dissolved oxygen (DO) concentration are the most important factors affecting aerobic denitrification process, however, the effects of those on the mix-cultured aerobic denitrification process are still ambiguous. A mathematical model based on the framework of activated sludge model No. 3 (ASM3) was proposed for simulating nitrogen removal in an aerobic denitrification SBR process via anoxic/aerobic denitrification. AQUASIM 2.1G was employed for parameter estimation, sensitivity analysis and model calibration, as well as model validation. Ultimately, the impacts of the C/N ratio and the DO concentration on the aerobic denitrification process were revealed by the validated model. The model proposed well described nitrogen removal in an aerobic denitrification SBR process. The total nitrogen (TN) removal efficiency of the process increased with the increasing of C/N ratio and the decreasing of DO concentration. C/N ratio impacted the synthesis of cell internal storage products (XSTO), and the effects of DO concentration on the process resulted from the competition with substrate between heterotrophs and aerobic denitrifiers. High C/N ratio was preferred, however, the DO concentration should be maintained at a relatively lower level under the premise of ensuring the aerobic condition.

A sesquiterpenoid from Ligularia pleurocaulis modulated macrophages polarisation through TLR4 pathway.

An eremophilane-type sesquiterpenoid (EPS), 3-oxo-eremophila-1,7(11)-dien-12,8ß-olide, has been isolated from anti-inflammatory folk herbs, Ligularia pleurocaulis. The aim of present study is to explore protective effects of EPS on lipopolysaccharide (LPS)-induced inflammatory responses in acute lung injury (ALI). EPS treatments (40 and 80 mg/kg) significantly ameliorated LPS-stimulated pathological changes in lungs. Furthermore, in vivo and in vitro mechanism studies suggest that EPS exerts its protective effects on LPS-induced ALI by regulating macrophage polarisation via suppression of TLR4/MyD88-mediated MAPK and NF-κB signaling pathways, and EPS may be useful for the prevention on ALI in the clinical setting.