Zinc Chemistries of Hybrid Electrolytes in Zinc Metal Batteries: From Solvent Structure to Interfaces.

Along with the booming research on zinc metal batteries (ZMBs) in recent years, operational issues originated from inferior interfacial reversibility have become inevitable. Presently, single-component electrolytes represented by aqueous solution, "water-in-salt," solid, eutectic, ionic liquids, hydrogel, or organic solvent system are hard to undertake independently the task of guiding the practical application of ZMBs due to their specific limitations. The hybrid electrolytes modulate microscopic interaction mode between Zn2+ and other ions/molecules, integrating vantage of respective electrolyte systems. They even demonstrate original Zn2+ mobility pattern or interfacial chemistries mechanism distinct from single-component electrolytes, providing considerable opportunities for solving electromigration and interfacial problems in ZMBs. Therefore, it is urgent to comprehensively summarize the zinc chemistries principles, characteristics, and applications of various hybrid electrolytes employed in ZMBs. This review begins with elucidating the chemical bonding mode of Zn2+ and interfacial physicochemical theory, and then systematically elaborates the microscopic solvent structure, Zn2+ migration forms, physicochemical properties, and the zinc chemistries mechanisms at the anode/cathode interfaces in each type of hybrid electrolytes. Among of which, the scotoma and amelioration strategies for the current hybrid electrolytes are actively exposited, expecting to provide referenceable insights for further progress of future high-quality ZMBs.

Integrating metabolomics with network pharmacology to reveal the mechanism of Poria cocos in hyperuricemia treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperuricemia is a chronic condition characterized by persistently elevated uric acid levels, often leading to gouty arthritis and renal insufficiency. Poria cocos F.A.Wolf, a traditional Chinese medicinal herb, possesses notable diuretic and anti-inflammatory properties and is widely used to treat edema, inflammation, viral infections, and tumors. Recent studies suggest that Poria cocos has the potential to lower uric acid levels and mitigate kidney damage, making it a promising candidate for hyperuricemia treatment. However, its pharmacological mechanisms require further exploration. AIM OF THE STUDY: This study aims to elucidate the mechanisms by which Poria cocos alleviates hyperuricemia, using metabolomics and network pharmacology approaches. MATERIALS AND METHODS: Hyperuricemia was induced in rats via a high-yeast diet combined with potassium oxonate. The effects of Poria cocos were assessed by measuring serum uric acid, creatinine, urea nitrogen levels, hepatic xanthine oxidase activity, and renal tissue morphology. Non-targeted metabolomics was employed to identify differential metabolites and explore the metabolic pathways involved in its therapeutic effects. Network pharmacology was utilized to analyze potential targets and signaling pathways, which were validated through molecular docking and ELISA analysis. RESULTS: Poria cocos extract significantly reduced serum uric acid, creatinine, and urea nitrogen levels, inhibited xanthine oxidase activity, and attenuated kidney damage. Metabolomics combined with network pharmacology identified xanthine dehydrogenase and fatty acid synthase as key targets, while purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis were identified as critical pathways. ELISA confirmed that Poria cocos suppressed xanthine dehydrogenase and fatty acid synthase expression in hyperuricemic rats. Molecular docking further verified strong binding interactions between core compounds and key targets. CONCLUSIONS: Poria cocos alleviates hyperuricemia by modulating multiple compounds, targets, and pathways. Through network pharmacology and metabolomics, it reveals that Poria cocos selectively regulates xanthine dehydrogenase and fatty acid synthase, influencing purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis pathways. These findings provide insights into its therapeutic mechanisms, supporting the clinical application of Poria cocos in treating metabolic disorders and kidney damage associated with hyperuricemia.

MYO6 contributes to tumor progression and enzalutamide resistance in castration-resistant prostate cancer by activating the focal adhesion signaling pathway.

BACKGROUND: Enzalutamide (Enz) resistance is a poor prognostic factor for patients with castration-resistant prostate cancer (CRPC), which often involves aberrant expression of the androgen receptor (AR). Myosin VI (MYO6), one member of the myosin family, plays an important role in regulating cell survival and is highly expressed in prostate cancer (PCa). However, whether MYO6 is involved in Enz resistance in CRPC and its mechanism remain unclear. METHODS: Multiple open-access databases were utilized to examine the relationship between MYO6 expression and PCa progression, and to screen differentially expressed genes (DEGs) and potential signaling pathways associated with the MYO6-regulated Enz resistance. Both in vitro and in vivo tumorigenesis assays were employed to examine the impact of MYO6 on the growth and Enz resistance of PCa cells. Human PCa tissues and related clinical biochemical data were utilized to identify the role of MYO6 in promoting PCa progression and Enz resistance. The molecular mechanisms underlying the regulation of gene expression, PCa progression, and Enz resistance in CRPC by MYO6 were investigated. RESULTS: MYO6 expression increases in patients with PCa and is positively correlated with AR expression in PCa cell lines and tissues. Overexpression of AR increases MYO6 expression to promote PCa cell proliferation, migration and invasion, and to inhibit PCa cell apoptosis; whereas knockdown of MYO6 expression reverses these outcomes and enhances Enz function in suppressing the proliferation of the Enz- sensitive and resistant PCa cells both in vitro and in vivo. Mechanistically, AR binds directly to the promoter region (residues - 503 to - 283 base pairs) of MYO6 gene and promotes its transcription. Furthermore, MYO6 activates focal adhesion kinase (FAK) phosphorylation at tyrosine-397 through integrin beta 8 (ITGB8) modulation to promote PCa progression and Enz resistance. Notably, inhibition of FAK activity by Y15, an inhibitor of FAK, can resensitize CRPC cells to Enz treatment in cell lines and mouse xenograft models. CONCLUSIONS: MYO6 has pro-tumor and Enz-resistant effects in CRPC, suggesting that targeting MYO6 may be beneficial for ENZ-resistant CRPC therapy through the AR/MYO6/FAK signaling pathway.

Effect of glyceryl monopalmitate on the gelatinization, rheological and retrogradation properties of Japonica rice starch.

BACKGROUND: Starch-based food is easy to retrograde during cold storage after gelatinization, which leads to quality fission and a relatively short shelf life. Some lipids can effectively enhance the storage stability of starch gels by the formation of starch-lipid complexes. The present study aimed to investigate the effects of glyceryl monopalmitate (GMP) on gelatinization, rheological and retrogradation properties of Japonica rice starch (JS) at different conditions and to analyze the correlation between the physical-chemical properties and structural characteristics of the JS-GMP complex. RESULTS: The addition of GMP to JS could retard the process of starch gelatinization through forming JS-GMP complexes. The resulting JS-GMP pastes were typical pseudoplastic fluids with shear thinning, and their solid-like properties were prominent (tan δ < 1). In addition, the retrogradation of JS-GMP complex was more inhibited during storage at -18 than at 4 °C. The added amount of GMP was negatively and highly associated with the minimum viscosity, consistency coefficient, hardness and elasticity, whereas it was positively and highly correlated with the breakdown value, fluid characteristic index and relative crystallinity. The relative crystallinity of JS was affected by GMP in an approximate dose-dependent manner. CONCLUSION: The addition of GMP can influence the gelatinization properties, rheological properties and retrogradation characteristics of JS, and the formation of JS-GMP complex could improve the quality and storage stability of starch gel, which provides ideas for the quality control of starch-based food. © 2024 Society of Chemical Industry.

Novel design of hollow carbon nanocage modified with nanotubes as a bifunctional electrocatalyst for high performance Zn-air batteries.

Microcavities play a crucial role as microreactors in the transport of molecular/ionic guests and the exposure of active sites, thus significantly influencing the electrocatalytic performance. This study prepares Co/N-codoped hollow carbon (HT-CoN/C) with surface-distributed carbon nanotubes by pyrolysis of PDA-coated Zn/Co bimetallic ZIF (BM-ZIF@PDA). Benefiting from the hierarchical porous structure, high specific surface area (307.17 m2 g-1) and abundant Co clusters, the HT-CoN/C exhibits remarkable bifunctional oxygen electrocatalytic activity with an overpotential of the ORR/OER processes (ΔE = 0.703 V). The density functional theory (DFT) calculations also verify that the configuration of C-coated N-coordinated Co clusters (Co4-Nx) affect the electrocatalytic activity of ORR and OER, illustrating the source of the excellent oxygen electrocatalytic activity of HT-CoN/C. The aqueous rechargeable zinc-air battery (RZAB) using HT-CoN/C as the air electrode is characterized by a superior peak power density (175 mW cm-2), a prolonged cycle life (1230 cycles/410 h at 5.0 mA cm-2) and a high open-circuit voltage (1.47 V). Meanwhile, the flexible solid-state RZAB assembled by the HT-CoN/C also exhibits a higher peak power density (117 mW cm-2) and an excellent bending performance. This work is extremely valuable for the design and synthesis of Co/N co-doped carbon electrocatalysts.

Sensing steroid hormone 17α-hydroxypregnenolone by GPR56 enables protection from ferroptosis-induced liver injury.

G protein-coupled receptors (GPCRs) mediate most cellular responses to hormones, neurotransmitters, and environmental stimulants. However, whether GPCRs participate in tissue homeostasis through ferroptosis remains unclear. Here we identify that GPR56/ADGRG1 renders cells resistant to ferroptosis and deficiency of GPR56 exacerbates ferroptosis-mediated liver injury induced by doxorubicin (DOX) or ischemia-reperfusion (IR). Mechanistically, GPR56 decreases the abundance of phospholipids containing free polyunsaturated fatty acids (PUFAs) by promoting endocytosis-lysosomal degradation of CD36. By screening a panel of steroid hormones, we identified that 17α-hydroxypregnenolone (17-OH PREG) acts as an agonist of GPR56 to antagonize ferroptosis and efficiently attenuates liver injury before or after insult. Moreover, disease-associated GPR56 mutants were unresponsive to 17-OH PREG activation and insufficient to defend against ferroptosis. Together, our findings uncover that 17-OH PREG-GPR56 axis-mediated signal transduction works as a new anti-ferroptotic pathway to maintain liver homeostasis, providing novel insights into the potential therapy for liver injury.

The triglyceride glucose related index is an indicator of Sarcopenia.

The triglyceride glucose (TyG) related index, a metric used to evaluate assessing insulin resistance (IR), has received limited attention in its association with sarcopenia. Our study aims to explore the predictive potential of the TyG index for sarcopenia. This study utilized data from the China Health and Retirement Longitudinal Study, a nationally representative, community-based cohort study, including a sample size of 10,537 participants aged 45 years and older. Associations between TyG related index and sacopenia was explored using multivariate logistic regression. Analysis of the predictive value of TyG related index for sarcopenia using receiver-operating characteristic curve (ROC). We evaluated the correlation between the TyG related index and the risk of sarcopenia using Cox proportional hazards models. Additionally, we utilized restricted cubic spline (RCS) regression analyses to explore the connections between the TyG-related index and sarcopenia. Logistic regression analysis showed an association between TyG (OR 0.961[0.955,0.968], P < 0.001), TyG-body mass index (TyG-BMI) (OR 0.872[0.867,0.878], P < 0.001), TyG- waist circumference (TyG-WC) (OR 0.896[0.890,0.902], P < 0.001) and sarcopenia. The results of the ROC analysis indicated that the area under the curve values for TyG, TyG-BMI, and TyG-WC were 0.659, 0.903, and 0.819, respectively. Compared to those without sarcopenia, patients with sarcopenia had a 37.7% (HR 0.623[0.502,0.774], P < 0.001), 4.8% (HR 0.952[0.947,0.958], P < 0.001), and 0.4% (HR 0.996[0.995,0.996], P < 0.001) lower risk with increasing TyG, TyG-BMI, and TyG-WC, respectively. RCS results show nonlinear relationship between TyG-BMI (P < 0.001) and TyG-WC (P < 0.001) and risk of sarcopenia. We observed a correlation between the TyG-related index and sarcopenia, with the TyG-BMI index demonstrating strong predictive capability for sarcopenia.

Transformable Soft Gripper: Uniting Grasping and Suction for Amphibious Cross-Scale Objects Grasping.

Robotic grasping plays a pivotal role in real-world interactions for robots. Existing grippers often limit functionality to a single grasping mode-picking or suction. While picking handles smaller objects and suction adapts to larger ones, integrating these modes breaks scale boundaries, expanding the robot's potential in real applications. This article introduces grasping modes transformable soft gripper capable of achieving amphibious cross-scale objects grasping. Despite its compact and fully scalable design (20 mm in diameter prototype), it morphs into two configurations, gripping objects from 10% (2 mm) to over 1000% (200 mm) of its size, spanning a vast 100-fold range. To enhance its grasping efficacy, we derived theoretical analytical models for the two distinct grasping modes. Subsequently, we present a detailed illustration of the gripper's fabrication process. Experimental validation demonstrates the gripper's success in attaching or detaching everyday items and industrial products, achieving high success rates in both air and underwater scenarios. Amphibious grasping and card manipulation demonstrations underscore the practicality of this transformative soft robotics approach.

A pH-responsive fluorescent film with the smartphone-assistance for real-time and visual detection of food freshness.

Monitoring food freshness is considerably important for food safety. In this study, a smart pH-responsive fluorescence hydroxypropyl methyl cellulose-κ-carrageenan-fluorescein isothiocyanate-NH2-CaAl2O4 (H-K-F-N) film was prepared. Taking synergetic advantage of the pH-dependent behavior of fluorescein isothiocyanate dye and the luminescence characteristics of calcium aluminate phosphor, the film exhibited a unique strong pH-responsive fluorescence with an exceptional linear relationship (correlation coefficient, R2 = 0.9993) across a wide pH rang of 2.0-12.0. Moreover, the H-K-F-N film, as a smart sensor, could be used to estimate the total volatile basic nitrogen and total viable count through fluorescence intensity based on the partial least squares regression model and support vector machine regression, respectively. Leveraging the relationship between the fluorescent image's digital signals and food freshness indicators, a smartphone-assisted system was developed. These results demonstrated that H-K-F-N film is promising for applications in intelligent food packaging and food safety monitoring.

Subthalamic Nucleus Deep Brain Stimulation for Meige Syndrome: Long-Term Outcomes and Analysis of Prognostic Factors.

BACKGROUND AND OBJECTIVES: The aim of this study was to explore the impacts of subthalamic nucleus deep brain stimulation (STN-DBS) on both motor and nonmotor symptoms in individuals with Meige syndrome, as well as further investigates prognostic factors for long-term postoperative outcomes. METHODS: We retrospectively reviewed a consecutive cohort of patients with intractable Meige syndrome who underwent STN-DBS at our center from January 2016 to July 2023. Motor function, quality of life, neuropsychological status, and mood state were evaluated with standardized scales at baseline and every 3 to 6 months thereafter. Univariate and multivariate linear regression analyses were used to determine independent risk factors that affect long-term motor function after STN-DBS. RESULTS: Fifty-five patients were ultimately analyzed with a mean follow-up of 62.1 ± 25.7 months. At the final postoperative assessment, movement and disability scores of the Burke-Fahn-Marsden Dystonia Rating Scale demonstrated improvements of 61% (P < .001) and 57% (P < .001), respectively. Postoperative scores on the 36-item Short-Form General Health Survey showed significant improvement from baseline. Global cognitive function and neuropsychological status remained stable during continuous neurostimulation. Multivariate linear regression analysis revealed that longer disease duration (standardized ß coefficient = -0.294, 95% CI -0.039 to -0.007, P = .006), older age at surgery (standardized ß coefficient = -0.382, 95% CI -0.014 to -0.004, P = .001), and smaller volume of tissue activated within the sensorimotor subregion of STN (standardized ß coefficient = 0.309, 95% CI 0.001-0.004, P = .004) were independently correlated with poorer long-term motor performance. CONCLUSION: Bilateral STN-DBS is an effective, safe, and promising treatment option for Meige syndrome, which can improve motor function and quality of life without cognitive and mood side effects. Early diagnosis, prompt intervention, and accurate lead placement in the dorsolateral STN are crucial to optimize long-term therapeutic outcomes.

Sniffing can be initiated by dopamine's actions on ventral striatum neurons.

Sniffing is a motivated behavior displayed by nearly all terrestrial vertebrates. While sniffing is associated with acquiring and processing odors, sniffing is also intertwined with affective and motivated states. The neuromodulatory systems which influence the display of sniffing are unclear. Here, we report that dopamine release into the ventral striatum is coupled with bouts of sniffing and that stimulation of dopaminergic terminals in these regions drives increases in respiratory rate to initiate sniffing whereas inhibition of these terminals reduces respiratory rate. Both the firing of individual neurons and the activity of post-synaptic D1 and D2 receptor-expressing neurons in the ventral striatum are also coupled with sniffing and local antagonism of D1 and D2 receptors squelches sniffing. Together, these results support a model whereby sniffing can be initiated by dopamine's actions upon ventral striatum neurons. The nature of sniffing being integral to both olfaction and motivated behaviors implicates this circuit in a wide array of functions.

Chemical structure and prebiotic activity of a Dictyophora indusiata polysaccharide fraction.

This study aimed to investigate the chemical structure and prebiotic activity of a Dictyophora indusiata polysaccharide fraction DIP0p. Our results indicated that DIP0p belongs to a heteropolysaccharide composed of glucose, galactose, mannose and xylose, accounting for 53.25 %, 24.18 %, 19.19 % and 3.37 %, respectively. Methylation and NMR results suggested that the main glycosidic bonds of DIP0p is →3)-Glcp-(1 â†’ with →4)-Glcp-(1→, →3,4)-Glcp-(1→, →3,4)-Galp-(1 â†’ and →6)-Manp-(1 â†’ branches. In addition, DIP0p increased the abundance of benificial bacteria during the in vitro fecal fermentation, including Phascolarctobacterium, Parabacteroides and Bifidobacterium. It is remarkable that DIP0p improved the level of acetic acid, propionic acid, and butyric acid of the fermentation system, which were 1.31, 1.52, and 2.64 folds higher than the Controls, respectively. In summary, this study comprehensively analyzed the structure and probiotic activity of DIP0p, which providing a theoretical basis for the development of the functional foods.

Identification of the factors influencing speeding behaviour of food delivery e-bikers in China with the naturalistic cycling data.

With the rapid growth of the gig economy in China, millions of food delivery e-bikers are making their living by rushing on the street. Speeding is one of their most common risky riding behaviours, leading to severe traffic crashes. Based on 2-month naturalistic cycling data of 46 full-time food delivery e-bikers in Changsha, their speeding behaviour is deeply studied with the individual daily speeding proportion being taken as the speeding indicator. A beta regression model is built to identify the factors significantly influencing the indicator. The estimation results reveal that female riders, middle-aged riders and riders with a bachelor's degree are less likely to engage in speeding. The same result is indicated for those working longer or experiencing more crashes. Additionally, holidays and riding distance are found to have significantly positive influences. Finally, some countermeasures are proposed to prevent speeding among food delivery e-bikers.

Enhancing Activity and Stability of Pd-on-TiO2 Single-Atom Catalyst for Low-Temperature CO Oxidation through in Situ Local Environment Tailoring.

The development of efficient Pd single-atom catalysts for CO oxidation, crucial for environmental protection and fundamental studies, has been hindered by their limited reactivity and thermal stability. Here, we report a thermally stable TiO2-supported Pd single-atom catalyst that exhibits enhanced intrinsic CO oxidation activity by tunning the local coordination of Pd atoms via H2 treatment. Our comprehensive characterization reveals that H2-treated Pd single atoms have reduced nearest Pd-O coordination and form short-distanced Pd-Ti coordination, effectively stabilizing Pd as isolated atoms even at high temperatures. During CO oxidation, partial replacement of the Pd-Ti coordination by O or CO occurs. This unique Pd local environment facilitates CO adsorption and promotes the activity of the surrounding oxygen species, leading to superior catalytic performance. Remarkably, the turnover frequency of the H2-treated Pd single-atom catalyst at 120 °C surpasses that of the O2-treated Pd single-atom catalyst and the most effective Pd/Pt single-atom catalysts by an order of magnitude. These findings open up new possibilities for the design of high-performance single-atom catalysts for crucial industrial and environmental applications.

The prevalence of neuropsychiatric symptoms and correlation with MRI findings in CADASIL patients.

OBJECTIVE: To assess the prevalence, timing, and functional impact of neuropsychiatric symptoms in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to assess whether these neuropsychiatric symptoms are associated with magnetic resonance imaging (MRI) features of the patients. METHODS: Our study included a total of 78 patients with CADASIL. To assess neuropsychiatric symptoms, we evaluated the caregivers using the Neuropsychiatric Inventory (NPI). Patients were considered to have an irritability, depression, apathy, aggression, or anxiety disorder if they scored ≥1 in the NPI. Subsequently, we conducted a more detailed assessment of irritability, depression, apathy, aggression, and anxiety. Multivariate logistic regression was employed to analyze the relationships between neuropsychiatric symptoms and clinical/MRI features in the patients. RESULTS: Overall, 57.69% of patients with CADASIL experienced neuropsychiatric symptoms. Among these symptoms, irritability was the most prevalent (52.56%), followed by depression (19.23%), apathy (17.95%), aggression (7.69%), and anxiety (6.41%). The mean age of onset for irritability was the youngest, followed by anxiety, apathy, aggression, and depression. Among patients with both stroke/TIA and neuropsychiatric symptoms, 31.03% reported experiencing neuropsychiatric symptoms prior to stroke/TIA. Furthermore, both irritability and apathy had a negative impact on the patients' daily functioning. Additionally, there was a correlation between the presence of neuropsychiatric symptoms and the patients' MRI lesion burden. INTERPRETATION: Our study has discovered that neuropsychiatric symptoms are highly prevalent in patients with CADASIL and may occur before cerebrovascular events, suggesting that neuropsychiatric symptoms of CADASIL deserve more attention and earlier exploration.

Low frequency sinusoidal electromagnetic fields promote the osteogenic differentiation of rat bone marrow mesenchymal stem cells by modulating miR-34b-5p/STAC2.

Electromagnetic fields (EMFs) have emerged as an effective treatment for osteoporosis. However, the specific mechanism underlying their therapeutic efficacy remains controversial. Herein, we confirm the pro-osteogenic effects of 15 Hz and 0.4-1 mT low-frequency sinusoidal EMFs (SEMFs) on rat bone marrow mesenchymal stem cells (BMSCs). Subsequent miRNA sequencing reveal that miR-34b-5p is downregulated in both the 0.4 mT and 1 mT SEMFs-stimulated groups. To clarify the role of miR-34b-5p in osteogenesis, BMSCs are transfected separately with miR-34b-5p mimic and inhibitor. The results indicate that miR-34b-5p mimic transfection suppress osteogenic differentiation, whereas inhibition of miR-34b-5p promote osteogenic differentiation of BMSCs. In vivo assessments using microcomputed tomography, H&E staining, and Masson staining show that miR-34b-5p inhibitor injections alleviate bone mass loss and trabecular microstructure deterioration in ovariectomy (OVX) rats. Further validation demonstrates that miR-34b-5p exerts its effects by regulating STAC2 expression. Modulating the miR-34b-5p/STAC2 axis attenuate the pro-osteogenic effects of low-frequency SEMFs on BMSCs. These studies indicate that the pro-osteogenic effect of SEMFs is partly due to the regulation of the miR-34b-5p/STAC2 pathway, which provides a potential therapeutic candidate for osteoporosis.

Deep brain stimulation and pallidotomy in primary Meige syndrome: a prospective cohort study.

BACKGROUND: Primary Meige syndrome (PMS) is a rare form of dystonia, and comparative analysis of globus pallidus internal deep brain stimulation (GPi-DBS), subthalamic nucleus deep brain stimulation (STN-DBS), and pallidotomy has been lacking. This study aims to compare the efficacy, safety, and psychiatric features of GPi-DBS, STN-DBS, and pallidotomy in patients with PMS. METHODS: This prospective cohort study was divided into three groups: GPi-DBS, STN-DBS, and pallidotomy. Clinical assessments, including motor and non-motor domains, were evaluated at baseline and at 1 year and 3 years after neurostimulation/surgery. RESULTS: Ninety-eight patients were recruited: 46 patients received GPi-DBS, 34 received STN-DBS, and 18 underwent pallidotomy. In the GPi-DBS group, the movement score of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) improved from a mean (SE) of 13.8 (1.0) before surgery to 5.0 (0.7) (95% CI, -10.5 to -7.1; P < 0.001) at 3 years. Similarly, in the STN-DBS group, the mean (SE) score improved from 13.2 (0.8) to 3.5 (0.5) (95% CI, -10.3 to -8.1; P < 0.001) at 3 years, and in the pallidotomy group, it improved from 14.9 (1.3) to 6.0 (1.1) (95% CI, -11.3 to -6.5; P < 0.001) at 3 years. They were comparable therapeutic approaches for PMS that can improve motor function and quality of life without non-motor side effects. CONCLUSIONS: DBS and pallidotomy are safe and effective treatments for PMS, and an in-depth exploration of non-motor symptoms may be a new entry point for gaining a comprehensive understanding of the pathophysiology.

Upregulated SKP2 Empowers Epidermal Proliferation Through Downregulation of P27 Kip1.

BACKGROUND: Excessive growth of keratinocytes is the critical event in the etiology of psoriasis. However, the underlying molecular mechanism of psoriatic keratinocyte hyperproliferation is still unclear. OBJECTIVE: This study aimed to figure out the potential contributory role of S-phase kinase-associated protein 2 (SKP2) in promoting the hyperproliferation of keratinocytes in psoriasis. METHODS: We analyzed microarray data (GSE41662) to investigate the gene expression of SKP2 in psoriatic lesion skins compared with their adjacent non-lesional skin. Then, we further confirmed the mRNA and protein expression of SKP2 in human psoriatic skin tissues, imiquimod (IMQ)-induced psoriatic mice back skins and tumor necrosis factor α (TNF-α), interleukin (IL)-17A and IL-6-stimulated keratinocytes by using real-time quantitative polymerase chain reaction and western blot (WB). Furthermore, we explored the potential pathogenic role and its underlying cellular mechanism of SKP2 in promoting keratinocytes hyperproliferation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle detection, 5-ethynyl-2'-deoxyuridine staining and WB. Finally, we determined whether inhibition of SKP2 can effectively alleviate the keratinocytes hyperproliferation in vivo. RESULTS: We identified that SKP2 is aberrantly upregulated in the psoriatic lesion skin and cytokines-stimulated keratinocytes. Moreover, upregulated SKP2 augments cytokines-induced keratinocytes hyperproliferation. Mechanistically, enhanced SKP2 increased the S phase ratio through inhibiting Cyclin-Dependent Kinase Inhibitor p27 (P27 Kip1) expression. Correspondingly, suppression of SKP2 with SMIP004 can significantly ease the epidermis hyperplasia in vivo. CONCLUSION: Our results suggest that elevated SKP2 can empower keratinocytes proliferation and psoriasis-like epidermis hyperplasia via downregulation of P27 Kip1. Therefore, targeting SKP2-P27 Kip1 axis might be a promising therapeutic strategy for the treatment of psoriasis in future.

Predictive Factors for Herpes Simplex Virus Reactivation in Patients with Trigeminal Neuralgia After Surgery.

OBJECTIVE: This study aimed to investigate the predictive factors associated with the reactivation of herpes simplex virus (HSV) in patients with trigeminal neuralgia after surgery and to determine whether there is a correlation between reactivation and surgical efficacy. METHODS: This study included 190 patients who underwent surgery between January 2020 and December 2021. Postoperative HSV reactivation was defined as the presence of perioral or gingival herpes and herpes labialis within 1 week postoperatively. Logistic regression analysis was used to evaluate clinical characteristics as potential predictors of HSV reactivation. Additionally, Spearman's rank correlation coefficient was used to determine any correlation between the postoperative Barrow Neurological Institute pain intensity score and HSV reactivation. RESULTS: Of the 190 patients, 56 (29.5%) experienced postoperative HSV reactivation. Both univariate and multivariate analyses identified several significant predictors of HSV reactivation, such as a history of HSV infection, previous trigeminal nerve-damaging surgery, the use of internal neurolysis as a surgical technique, and an operation time of ≥25 minutes. No significant correlation was found between HSV reactivation and pain relief, as measured by Barrow Neurological Institute scores. CONCLUSIONS: HSV reactivation was observed in a considerable proportion of patients with trigeminal neuralgia. Long operative times (≥25 minutes), the use of internal neurolysis as a surgical technique, a history of HSV infection, and previous trigeminal nerve-damaging surgery were identified as risk factors. Further research is needed to optimize surgical procedures and develop targeted management protocols to reduce the risk of HSV reactivation.

Bleomycin triggers chronic mechanical nociception by activating TRPV1 and glial reaction-mediated neuroinflammation via TSLP/TSLPR/pSTAT5 signals.

Chronic pain is a universal public health problem with nearly one third of global human involved, which causes significant distressing personal burden. After painful stimulus, neurobiological changes occur not only in peripheral nervous system but also in central nervous system where somatosensory cortex is important for nociception. Being an ion channel, transient receptor potential vanilloid 1 (TRPV1) act as an inflammatory detector in the brain. Thymic stromal lymphopoietin (TSLP) is a potent neuroinflammation mediator after nerve injury. Bleomycin is applied to treat dermatologic diseases, and its administration elicits local painful sensation. However, whether bleomycin administration can cause chronic pain remains unknown. In the present study, we aimed to investigate how mice develop chronic pain after receiving repeated bleomycin administration. In addition, the relevant neurobiological brain changes after noxious stimuli were clarified. C57BL/6 mice aged five- to six-weeks were randomly classified into two group, PBS (normal) group and bleomycin group which bleomycin was intradermally administered to back five times a week over a three-week period. Calibrated forceps testing was used to measure mouse pain threshold. Western blots were used to assess neuroinflammatory response; immunofluorescence assay was used to measure the status of neuron apoptosis, glial reaction, and neuro-glial communication. Bleomycin administration induced mechanical nociception and activated both TRPV1 and TSLP/TSLPR/pSTAT5 signals in mouse somatosensory cortex. Through these pathways, bleomycin not only activates glial reaction but also causes neuronal apoptosis. TRPV1 and TSLP/TSLPR/pSTAT5 signaling had co-labeled each other by immunofluorescence assay. Taken together, our study provides a new chronic pain model by repeated intradermal bleomycin injection by activating TRPV1 and glial reaction-mediated neuroinflammation via TSLP/TSLPR/pSTAT5 signals.