GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain: A Phase 3 Randomized Clinical Trial.

Importance: Many patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China. Objective: To evaluate the efficacy and safety of capsules containing γ-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP. Design, Setting, and Participants: This phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose. Intervention: In stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment. Main Outcomes and Measures: The primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences. Results: Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was -2.24 (1.55) for the 40-mg/d and -2.16 (1.79) for 80-mg/d groups and -1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common. Conclusions and Relevance: Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT04647773.

Scientific misconduct responsibility attribution: An empirical study on byline position and team identity in Chinese medical papers.

OBJECTIVE: The primary objective of this inquiry was to explore the nexus between authorship attribution in medical literature and accountability for scientific impropriety while assessing the influence of authorial multiplicity on the severity of sanctions imposed. METHODS: Probit regression models were employed to scrutinize the impact of authorship on assuming accountability for scientific misconduct, and unordered multinomial logistic regression models were used to examine the influence of authorship and the number of bylines on the severity of punitive measures. RESULTS: First authors and corresponding authors were significantly more likely to be liable for scientific misconduct than other authors and were more likely to be penalized particularly severely. Furthermore, a negative correlation was observed between the number of authors' affiliations and the severity of punitive measures. CONCLUSION: Authorship exerts a pronounced influence on the attribution of accountability in scientific research misconduct, particularly evident in the heightened risk of severe penalties confronting first and corresponding authors owing to their principal roles. Hence, scientific research institutions and journals must delineate authorship specifications meticulously, ascertain authors' contributions judiciously, bolster initiatives aimed at fostering scientific research integrity, and uphold an environment conducive for robust scientific inquiry.

The association of genetic polymorphisms within the dopaminergic system with nicotine dependence: A narrative review.

Nicotine, the main compound in cigarettes, leads to smoking addiction. Nicotine acts on the limbic dopamine reward loop in the midbrain by binding to nicotinic acetylcholine receptors, promoting the release of dopamine, and resulting in a rewarding effect or satisfaction. This satisfaction is essential for continued and compulsive tobacco use, and therefore dopamine plays a crucial role in nicotine dependence. Numerous studies have identified genetic polymorphisms of dopaminergic pathways which may influence susceptibility to nicotine addiction. Dopamine levels are greatly influenced by synthesis, storage, release, degradation, and reuptake-related genes, including genes encoding tyrosine hydroxylase, dopamine decarboxylase, dopamine transporter, dopamine receptor, dopamine 3-hydroxylase, catechol-O-methyltransferase, and monoamine oxidase. In this paper, we review research progress on the effects of polymorphisms in the above genes on downstream smoking behavior and nicotine dependence, to offer a theoretical basis for the elucidation of the genetic mechanism underlying nicotine dependence and future personalized treatment for smoking cessation.

Germline loss in C. elegans enhances longevity by disrupting adhesion between niche and stem cells.

Ageing and fertility are intertwined. Germline loss extends the lifespan in various organisms, termed gonadal longevity. However, the original longevity signal from the somatic gonad remains poorly understood. Here, we focused on the interaction between germline stem cells (GSCs) and their niche, the distal tip cells (DTCs), to explore the barely known longevity signal from the somatic gonad in C. elegans. We found that removing germline disrupts the cell adhesions between GSC and DTC, causing a significant transcriptomic change in DTC through hmp-2/ß-catenin and two GATA transcription factors, elt-3 and pqm-1 in this niche cell. Inhibiting elt-3 and pqm-1 in DTC suppresses gonadal longevity. Moreover, we further identified the TGF-ß ligand, tig-2, as the cytokine from DTC upon the loss of germline, which evokes the downstream gonadal longevity signalling throughout the body. Our findings thus reveal the source of the longevity signalling in response to germline removal, highlighting the stem cell niche as a critical signalling hub in ageing.

A 90-day subchronic exposure to heated tobacco product aerosol caused differences in intestinal inflammation and microbiome dysregulation in rats.

INTRODUCTION: Smoking is one of the most important predisposing factors of intestinal inflammatory diseases. Heated tobacco product (HTP) is a novel tobacco category that is claimed to deliver reduced chemicals to human those reported in combustible cigarette smoke (CS). However, the effect of HTP on intestine is still unknown. METHODS: In the framework of Organization for Economic Co-operation and Development guidelines 413 guidelines, Sprague-Dawley rats were exposed to HTP aerosol and CS for 13 weeks. The atmosphere was characterized and oxidative stress and inflammation of intestine were investigated after exposure. Furthermore, the faeces we performed with 16S sequencing and metabolomics analysis. RESULTS: HTP aerosol and CS led to obvious intestinal damage evidenced by increased intestinal pro-inflammatory cytokines and oxidative stress in male and female rats After HTP and CS exposure, the abundance that obviously changed were Lactobacillus and Turiciacter in male rats and Lactobacillus and Prevotella in female rats. HTP mainly induced the metabolism of amino acids and fatty acyls such as short-chain fatty acids and tryptophan, while CS involved into the main metabolism of bile acids, especially indole and derivatives. Although different metabolic pathways in the gut mediated by HTP and CS, both to inflammation and oxidative stress were ultimately induced. CONCLUSIONS: HTP aerosol and CS induced intestinal damage mediated by different gut microbiota and metabolites, while both lead to inflammation and oxidative stress. IMPLICATIONS: The concentration of various harmful components in heated tobacco product aerosol is reported lower than that of traditional cigarette smoke, however, its health risk impact on consumers remains to be studied. Our research findings indicate that heated tobacco product and cigarette smoke inhalation induced intestinal damage through different metabolic pathways mediated by gut microbiome, indicating the health risk of heated tobacco product in intestine.

The difference of addictive behavior of freebase nicotine and nicotine salts in mice base on an aerosol self-administration model.

INTRODUCTION: The distinctions in the biological impacts of distinct forms of nicotine have become a prominent subject of current research. However, relatively little research has been done on the addictive effects of different forms of nicotine. METHODS: The aerosol self-administration device was briefly characterized by determining aerosol concentration, particle size, and distributional diffusion of the aerosol. And the aerosol self-administration model was constructed at 1, 5, and 10 mg/mL of nicotine to select the appropriate nicotine concentration. Subsequently, the model was used to explore the differences in aerosol self-administration behavior of freebase nicotine and nicotine salts and the behavioral differences after withdrawal. RESULTS: We successfully constructed mouse aerosol self-administration models at 1, 5, and 10 mg/mL nicotine concentrations. In the study of the difference in addictive behaviors between freebase nicotine and nicotine salts, mice with freebase nicotine and different nicotine salts showed varying degrees of drug-seeking behavior, with nicotine benzoate showing the strongest reinforcement. During the withdrawal phase, nicotine salts mice showed more robust anxiety-like behaviors. CONCLUSIONS: These results confirm the successful development and stability of the nicotine aerosol self-administration model. Furthermore, they demonstrated that nicotine salts enhance drug-seeking behavior to a greater extent than freebase nicotine, with nicotine benzoate exhibiting the most significant effects. IMPLICATIONS: In this study, an aerosol self-administered model of mice was constructed, which can be used not only for comparing the effects of freebase nicotine and nicotine salts on the behavior, but also for other addictive drugs, such as fentanyl and cannabis. In addition, this study shows that nicotine salts may be more addictive compared to freebase nicotine, which is a reference for the future use of nicotine salts in tobacco products such as e-cigarettes.

Smoking-diseases correlation database: comprehensive analysis of the correlation between smoking and 422 diseases based on NHANES 2013-2018.

Background: Smoking is a risk factor for a wide range of diseases. Previous research has confirmed over 30 Smoking-Associated Diseases in diverse systems. There is limited research exploring the correlation among multiple diseases, with an absence of comprehensive investigations. Few studies concentrate on diseases exhibiting a negative correlation with smoking, wherein smokers demonstrate a lower prevalence. Objective: This study aimed to detect the correlation between smoking and other diseases using data from National Health and Nutrition Examination Surveys (NHANES) and construct a Smoking-Diseases Correlation Database (SDCD). The second aim is to obtain an extensive screening test for diseases that may be linked to smoking. Methods: 39,126 subjects' data from the NHANES 2013-2018 dataset were extracted. The baseline information, difference in blood routine and blood chemistry indicators between smokers and non-smokers, and diseases' correlation with smoking in four different models were analyzed by R. The data and statistics were aggregated into an online SDCD. Results: Our study reported 46 Smoking-Associated Diseases (SAD), including 29 Smoking Positively Associated Diseases (SPAD) and 17 Smoking Negatively Associated Diseases (SNAD). The SDCD of 422 diseases was constructed and can be accessed at https://chatgptmodel.shinyapps.io/sdcd/. Conclusion: Our findings revealed 46 SADs including 29 SPADs and 17 SNADs. We aggregated the statistics and developed online SDCD, advancing our understanding of the correlation between smoking and diseases.

Correction: UHPLC-MS/MS combined with microdialysis for simultaneous determination of nicotine and neurotransmitter metabolites in the rat hippocampal brain region: application to pharmacokinetic and pharmacodynamic study.

Correction for 'UHPLC-MS/MS combined with microdialysis for simultaneous determination of nicotine and neurotransmitter metabolites in the rat hippocampal brain region: application to pharmacokinetic and pharmacodynamic study' by Mingyu Zhu et al., Anal. Methods, 2024, https://doi.org/10.1039/d4ay00522h.

UHPLC-MS/MS combined with microdialysis for simultaneous determination of nicotine and neurotransmitter metabolites in the rat hippocampal brain region: application to pharmacokinetic and pharmacodynamic study.

Nicotine crosses the blood-brain barrier and interacts with nicotinic acetylcholine receptors, initiating a cascade of neurotransmitter effects with potential therapeutic implications for neurodegenerative conditions such as Alzheimer's and Parkinson's disease. The hippocampus, pivotal for cognitive processes, plays a crucial role in nicotine-mediated cognitive enhancement due to its abundant expression of nicotinic acetylcholine receptors, particularly the α7 subtype, which is heavily implicated in hippocampus-related behavioral functions and dysfunctions. However, the intricate process of nicotine metabolism within the hippocampus remains poorly understood, impeding our comprehension of how nicotine and its metabolites modulate neurotransmitter dynamics. To address this gap, we have developed and validated a novel methodology combining microdialysis with UHPLC-MS/MS, enabling simultaneous detection of 12 neurotransmitters, nicotine, and its seven metabolites within the rat hippocampus. The linearity range of the targeted compounds is satisfactory (R2 > 0.9970), with intra-day and inter-day precision not exceeding 12.7%, and accuracy ranging from -12.4% to 13.7%. Our findings reveal differential pharmacokinetics of nicotine and its metabolites in the α7KO group compared to the control group, characterized by heightened nicotine absorption and slower elimination and distribution in the former. Notably, the pharmacokinetic parameters of cotinine exhibit similarity across both groups. Studies investigating the impact of nicotine on monoamine neurotransmitters have elucidated its capacity to augment the release of dopamine, serotonin, norepinephrine, glutamate, and acetylcholine in the rat hippocampus. This integrated approach facilitates a comprehensive analysis of neurotransmitter alterations within the hippocampal region following nicotine administration, thereby providing robust technical support and scientific rationale for understanding the neurochemical effects of nicotine and its metabolites. Further exploration into the pharmacokinetics and pharmacodynamics of nicotine holds promise for uncovering novel therapeutic avenues in the management of neurodegenerative diseases such as Alzheimer's.

Difference in Rumor Dissemination and Debunking Before and After the Relaxation of COVID-19 Prevention and Control Measures in China: Infodemiology Study.

BACKGROUND: The information epidemic emerged along with the COVID-19 pandemic. While controlling the spread of COVID-19, the secondary harm of epidemic rumors to social order cannot be ignored. OBJECTIVE: The objective of this paper was to understand the characteristics of rumor dissemination before and after the pandemic and the corresponding rumor management and debunking mechanisms. This study aimed to provide a theoretical basis and effective methods for relevant departments to establish a sound mechanism for managing network rumors related to public health emergencies such as COVID-19. METHODS: This study collected data sets of epidemic rumors before and after the relaxation of the epidemic prevention and control measures, focusing on large-scale network rumors. Starting from 3 dimensions of rumor content construction, rumor propagation, and rumor-refuting response, the epidemic rumors were subdivided into 7 categories, namely, involved subjects, communication content, emotional expression, communication channels, communication forms, rumor-refuting subjects, and verification sources. Based on this framework, content coding and statistical analysis of epidemic rumors were carried out. RESULTS: The study found that the rumor information was primarily directed at a clear target audience. The main themes of rumor dissemination were related to the public's immediate interests in the COVID-19 field, with significant differences in emotional expression and mostly negative emotions. Rumors mostly spread through social media interactions, community dissemination, and circle dissemination, with text content as the main form, but they lack factual evidence. The preferences of debunking subjects showed differences, and the frequent occurrence of rumors reflected the unsmooth channels of debunking. The χ2 test of data before and after the pandemic showed that the P value was less than .05, indicating that the difference in rumor content before and after the pandemic had statistical significance. CONCLUSIONS: This study's results showed that the themes of rumors during the pandemic are closely related to the immediate interests of the public, and the emotions of the public accelerate the spread of these rumors, which are mostly disseminated through social networks. Therefore, to more effectively prevent and control the spread of rumors during the pandemic and to enhance the capability to respond to public health crises, relevant authorities should strengthen communication with the public, conduct emotional risk assessments, and establish a joint mechanism for debunking rumors.

Dual Regulation of Nicotine on NLRP3 Inflammasome in Macrophages with the Involvement of Lysosomal Destabilization, ROS and α7nAChR.

Nicotine, the primary alkaloid in tobacco products, has been shown to have immunoregulatory function in at least 20 diseases. The biological mechanism of action of nicotine immunoregulation is complex, resulting in an improvement of some disease states and exacerbation of others. Given the central role of the NLRP3 inflammasome in macrophages among multiple inflammatory diseases, this study examined how nicotine alters NLRP3 inflammasome activation in macrophages. NLRP3 inflammasome activation was examined mechanistically in the context of different nicotine dosages. We show NLRP3 inflammasome activation, apoptosis-associated speck-like protein (ASC) expression, caspase-1 activity and subsequent IL-1ß secretion were positively correlated with nicotine in a dose-dependent relationship, and destabilization of lysosomes and ROS production were also involved. At high concentrations of nicotine surpassing 0.25 mM, NLRP3 inflammasome activity declined, along with increased expression of the anti-inflammatory Alpha7 nicotinic acetylcholine receptor (α7nAChR) and the inhibition of TLR4/NF-κB signaling. Consequently, high doses of nicotine also reduced ASC expression, caspase-1 activity and IL-1ß secretion in macrophages. Collectively, these results suggest a dual regulatory function of nicotine on NLRP3 inflammasome activation in macrophages, that is involved with the pro-inflammatory effects of lysosomal destabilization and ROS production. We also show nicotine mediates anti-inflammatory effects by activating α7nAChR at high doses.

Determinants of mer Promoter Activity from Pseudomonas aeruginosa.

Since the MerR family is known for its special regulatory mechanism, we aimed to explore which factors determine the expression activity of the mer promoter. The Tn501/Tn21 mer promoter contains an abnormally long spacer (19 bp) between the -35 and -10 elements, which is essential for the unique DNA distortion mechanism. To further understand the role of base sequences in the mer promoter spacer, this study systematically engineered a series of mutant derivatives and used luminescent and fluorescent reporter genes to investigate the expression activity of these derivatives. The results reveal that the expression activity of the mer promoter is synergistically modulated by the spacer length (17 bp is optimal) and the region upstream of -10 (especially -13G). The spacing is regulated by MerR transcription factors through symmetrical sequences, and -13G presumably functions through interaction with the RNA polymerase sigma-70 subunit.

The Role of Nicotine Metabolic Rate on Nicotine Dependence and Rewarding: Nicotine Metabolism in Chinese Male Smokers and Male Mice.

The exact relationship between nicotine metabolism and dependence is not fully understood but is known to be influenced at a molecular level by genetic factors. A sample comprising 274 Chinese adult male smokers was categorized into groups based on their metabolic rates, namely fast, intermediate, and slow metabolizers. We then measured their smoking topography, evaluated their nicotine dependence, and assessed the rewarding effects. Based on these findings, we proposed the hypothesis that the rate of nicotine metabolism could influence the level of dopamine release which in turn had repercussions on the pleasurable and rewarding effects. To test this hypothesis, male mice were selected with different nicotine metabolic rates that closely resembled in the smoker group. We evaluated their nicotine dependence and rewarding effects through conditioned place preference and withdrawal symptom tests, supplemented with dopamine release measurements. In both animal and human, the slow metabolism group (SMG) required less nicotine to maintain a comparable level of dependence than the fast metabolism group (FMG). The SMG could achieve similar rewarding effects to FMG despite consuming less nicotine. Comparable dopamine levels released were therefore critical in setting the nicotine acquisition behavior in this animal model and also for the smokers tested. Our findings suggested that even within the same ethnicity of established smokers (Chinese Han), differences in nicotine metabolism were an important parameter to modulate the degree of nicotine dependence.

A study on the factors influencing the intention to receive booster shots of the COVID-19 vaccine in China based on the information frame effect.

Introduction: In the response to and prevention and control of the Novel coronavirus pneumonia, the COVID-19 vaccine does not provide lifelong immunity, and it is therefore important to increase the rate of booster shots of the COVID-19 vaccine. In the field of information health science, research has found that information frames have an impact in changing individual attitudes and health behaviors. Objective: This study focuses on the effects of different influencing factors on the public's willingness to receive the booster shots of the COVID-19 vaccine under two information frameworks. Methods: An online questionnaire was conducted to explore the effects of demographic characteristics, personal awareness, social relationships, risk disclosure, perceived booster vaccination protection rate, and duration of protection under the assumption of an information framework. T test and one-way analysis were used to testing the effect of variables. Results: (1) The persuasion effect under the gain frame is higher than that under the loss frame (B = 0.863 vs. B = 0.746); (2) There was no significant difference in subjects' intention of booster vaccination in terms of gender, age, income, occupation, educational background and place of residence. Whether family members received booster vaccination was strongly correlated with their intention of vaccination under the loss framework (p = 0.017, M = 4.63, SD = 0.664). (3) The higher the understanding of COVID-19, the higher the degree of compliance with the government's COVID-19 prevention and control measures, and the higher the willingness to strengthen vaccination; (4) Risk disclosure has a significant impact on people's willingness to receive COVID-19 booster shots (M = 2.48, under the loss framework; M = 2.44, under the gain framework); (5) Vaccine protection rate and duration of protection have an impact on people's willingness to vaccinate. Increased willingness to vaccinate when the protection rate of booster vaccine approaches 90% (M = 4.76, under the loss framework; M = 4.68, under the gain framework). When the vaccine protection period is 2 years, people are more willing to receive a booster vaccine; and the willingness to receive a booster shot is stronger under the loss framework (M = 4.60, SD = 0.721, p = 0.879). Conclusion: The impact of the information framework on COVID-19 vaccination intentions is different, and the disclosure of relevant health information should focus on the impact of the information framework and content on the public's behavior toward strengthening vaccination. Therefore, in the face of public health emergencies, public health departments, healthcare institutions, and other sectors can consider adopting the Gainful Information Framework tool to disseminate health information to achieve better persuasion and promote public health behavior change enhancing public health awareness, and promoting universal vaccination.

BLMP-1 is a critical temporal regulator of dietary-restriction-induced response in Caenorhabditis elegans.

The extrinsic diet and the intrinsic developmental programs are intertwined. Although extensive research has been conducted on how nutrition regulates development, whether and how developmental programs control the timing of nutritional responses remain barely known. Here, we report that a developmental timing regulator, BLMP-1/BLIMP1, governs the temporal response to dietary restriction (DR). At the end of larval development, BLMP-1 is induced and interacts with DR-activated PHA-4/FOXA, a key transcription factor responding to the reduced nutrition. By integrating temporal and nutritional signaling, the DR response regulates many development-related genes, including gska-3/GSK3ß, through BLMP-1-PHA-4 at the onset of adulthood. Upon DR, a precocious activation of BLMP-1 in early larval stages impairs neuronal development through gska-3, whereas the increase of gska-3 by BLMP-1-PHA-4 at the last larval stage suppresses WNT signaling in adulthood for DR-induced longevity. Our findings reveal a temporal checkpoint of the DR response that protects larval development and promotes adult health.

Improved Conductivity and in Situ Formed Heterojunction via Zinc Doping in CuBi2O4 for Photoelectrochemical Water Splitting.

As a photocathode with a band gap of about 1.8 eV, copper bismuthate (CuBi2O4) is a promising material for photoelectrochemical (PEC) water splitting. However, weak charge transfer capability and severe carrier recombination suppress the PEC performance of CuBi2O4. In this paper, the conductivity and carriers transport of CuBi2O4 are improved via introducing Zn2+ into the synthesis precursor of CuBi2O4, driving a beneficial 110 mV positive shift of onset potential in photocurrent. Detailed investigations demonstrate that the introduction of an appropriate amount of zinc leads to in situ segregation of ZnO which serves as an electron transport channel on the surface of CuBi2O4, forming heterojunctions. The synergistic effect of heterojunctions and doping simultaneously promotes the charge transfer and the carrier concentration. OCP experiment proves that ZnO/Zn-CuBi2O4 possesses better charge separation; the Mott-Schottky curve shows that the doping of Zn significantly enhances the carrier concentration; carrier lifetime calculated from time-resolved photoluminescence confirms faster extraction of carriers.

Cell death induced by nicotine in human neuroblastoma SH-SY5Y cells is mainly attributed to cytoplasmic vacuolation originating from the trans-Golgi network.

Humans are usually exposed to nicotine through the use of tobacco products. Although it is generally believed that nicotine is relatively harmless in tobacco consumption, it is, in fact, a toxic substance that warrants careful consideration of its potential toxicity. However, the current understanding of the neurotoxicity of nicotine is still very limited. In this study, we aim to reveal the toxic risk of nicotine to key target neuronal cells and its potential toxic mechanisms. The results showed that nicotine induced cell death, ROS increase, mitochondrial membrane potential decrease, and DNA damage in SH-SY5Y human neuroblastoma cells at millimolar concentrations, but did not cause toxic effects at the physiological concentration. These toxic effects were accompanied by cytoplasmic vacuolation. The inhibition of cytoplasmic vacuolation by bafilomycin A1 greatly reduced nicotine-induced cell death, indicating that cytoplasmic vacuolation is the key driving factor of cell death. These cytoplasmic vacuoles originated from the trans-Golgi network (TGN) and expressed microtubule-associated protein 1 light chain 3-II (LC3-II) and lysosomal associated membrane protein 1(LAMP1). The presence of LC3-II and LAMP1 within these vacuoles serves as evidence of compromised TGN structure and function. These findings provide valuable new insights into the potential neurotoxic risk and mechanisms of nicotine.

Testicular tissue response following a 90-day subchronic exposure to HTP aerosols and cigarette smoke in rats.

Background: Researches have shown that chronic inhalation of cigarette smoke (CS) disrupts male reproductive system, but it is unclear about the mechanisms behind reproductive damages by tobacco toxicants in male rats. This study was designed to explore the effects of heated tobacco products (HTP) aerosols and CS exposure on the testicular health of rats. Materials and Methods: Experiments were performed on male SD rats exposed to filtered air, HTP aerosols at 10 µg/L, 23 µg/L, and 50 µg/L nicotine-equivalent contents, and also CS at 23 µg/L nicotine-equivalent content for 90 days in five exposure groups (coded as sham, HTP_10, HTP_23, HTP_50 and Cig_23). The expression of serum testosterone, testicular tissue inflammatory cytokines (IL-1ß, IL-6, IL-10, TNF-α), reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA), NLRP3 inflammasome-related mRNAs and proteins (NLRP3, ASC, and Caspase-1), the degree of pyroptosis and histopathology were investigated. Results: The results demonstrated that HTP_50 and Cig_23 caused varying degrees of oxidative damage to rat testis, resulting in a decrease of sperm quantity and serum testosterone contents, an increase in the deformity rate, expression levels of proinflammatory cytokines, and NLRP3 inflammasome-related mRNA, and an increase in the NLRP3, ASC, and Caspase-1-immunopositive cells, pyroptosis cell indices, and histopathological damage in the testes of rats. Responses from the HTP_10 and HTP_23 groups were less than those found in the above two exposure groups. Conclusion: These findings indicate that HTP_50 and Cig_23 induced oxidative stress in rat testes, induced inflammation and pyroptosis through the ROS/NLRP3/Caspase-1 pathway, and destroyed the integrity of thetesticular tissue structure.

Pharmacokinetic differences in nicotine and nicotine salts mediate reinforcement-related behavior: an animal model study.

Since their introduction in the United States and Europe in 2007, electronic cigarettes (E-Cigs) have become increasingly popular among smokers. Nicotine, a key component in both tobacco and e-cigarettes, can exist in two forms: nicotine-freebase (FBN) and nicotine salts (NS). While nicotine salt is becoming more popular in e-cigarettes, the effect of nicotine salts on reinforcement-related behaviors remains poorly understood. This study aimed to compare the reinforcing effects of nicotine and nicotine salts in animal models of drug self-administration and explore potential mechanisms that may contribute to these differences. The results demonstrated that three nicotine salts (nicotine benzoate, nicotine lactate, and nicotine tartrate) resulted in greater reinforcement-related behaviors in rats compared to nicotine-freebase. Moreover, withdrawal-induced anxiety symptoms were lower in the three nicotine salt groups than in the nicotine-freebase group. The study suggested that differences in the pharmacokinetics of nicotine-freebase and nicotine salts in vivo may explain the observed behavioral differences. Overall, this study provides valuable insights into the reinforcing effects of nicotine as well as potential differences between nicotine-freebase and nicotine salts.

Ultrahigh Electrostrictive Effect in Lead-Free Ferroelectric Ceramics Via Texture Engineering.

The electrostrictive effect, which induces strain in ferroelectric ceramics, offers distinct advantages over its piezoelectric counterpart for high-precision actuator applications, including anhysteretic behavior even at high frequencies, rapid reaction times, and no requirement for poling. Historically, commercially available electrostrictive materials have been lead oxide-based. However, global restrictions on the use of lead in electronic components necessitate the exploration of lead-free electrostrictive ceramics with a high strain performance. Although various engineering strategies for producing materials with high strain have been proposed, they typically come at the expense of increased strain hysteresis. Here, we describe the extraordinary electrostrictive response of (Ba0.95Ca0.05)(Ti0.88Sn0.12)O3 (BCTS) ceramics with ultrahigh electrostrictive strain and negligible hysteresis achieved through texture engineering leveraging the anisotropic intrinsic lattice contribution. The BCTS ceramics exhibit a high unipolar strain of 0.175%, a substantial electrostrictive coefficient Q33 of 0.0715 m4 C-2, and an ultralow hysteresis of less than 0.8%. Notably, the Q33 value is three times greater than that of high-performance lead-based Pb(Mg1/3Nb2/3)O3 electrostrictive ceramics. Multiscale structural analyses demonstrate that the electrostrictive effect dominates the BCTS strain response. This research introduces a novel approach to texture engineering to enhance the electrostrictive effect, offering a promising paradigm for future advancements in this field.