Predicting radiofrequency thermocoagulation surgical outcomes in refractory focal epilepsy patients using functional coupled neural mass model.

Objective: The success rate of achieving seizure freedom after radiofrequency thermocoagulation surgery for patients with refractory focal epilepsy is about 20-40%. This study aims to enhance the prediction of surgical outcomes based on preoperative decisions through network model simulation, providing a reference for clinicians to validate and optimize surgical plans. Methods: Twelve patients with epilepsy who underwent radiofrequency thermocoagulation were retrospectively reviewed in this study. A coupled model based on model subsets of the neural mass model was constructed by calculating partial directed coherence as the coupling matrix from stereoelectroencephalography (SEEG) signals. Multi-channel time-varying model parameters of excitation and inhibitions were identified by fitting the real SEEG signals with the coupled model. Further incorporating these model parameters, the coupled model virtually removed contacts destroyed in radiofrequency thermocoagulation or selected randomly. Subsequently, the coupled model after virtual surgery was simulated. Results: The identified excitatory and inhibitory parameters showed significant difference before and after seizure onset (p < 0.05), and the trends of parameter changes aligned with the seizure process. Additionally, excitatory parameters of epileptogenic contacts were higher than that of non-epileptogenic contacts, and opposite findings were noticed for inhibitory parameters. The simulated signals of postoperative models to predict surgical outcomes yielded an area under the curve (AUC) of 83.33% and an accuracy of 91.67%. Conclusion: The multi-channel coupled model proposed in this study with physiological characteristics showed a desirable performance for preoperatively predicting patients' prognoses.

Radiological characteristics predicting early poor drug response in patients with hemifacial spasm.

OBJECTIVES: Patients with hemifacial spasm (HFS) often resort to botulinum toxin injections or microvascular decompression surgery when medication exhibits limited effectiveness. This study aimed to identify MRI and demographic factors associated with poor drug response at an early stage in patients with HFS. METHODS: We retrospectively included patients with HFS who underwent pre-therapeutic MRI examination. The presence, location, severity, and the offending vessels of neurovascular compression were blindly evaluated using MRI. Drug responses and clinical data were obtained from the medical notes or phone follow-ups. Logistic regression analysis was performed to identify potential factors. RESULTS: A total of 116 patients were included, with an average age at the time of first examination of 50.4 years and a median duration of onset of 18 months. Forty-nine (42.2%) patients reported no symptom relief. Thirty-seven (31.9%) patients reported poor symptom relief. Twenty-two (19.0%) patients reported partial symptom relief. Eight (6.9%) patients achieved complete symptom relief. The factors that were statistically significant associated with poor drug responses were contact in the attach segment of the facial nerve and aged 70 and above, with an odds ratio of 7.772 (p = 0.002) and 0.160 (p = 0.028), respectively. CONCLUSIONS: This study revealed that mild compression in the attach segment of the facial nerve in pre-therapeutic MRI increases the risk of poor drug responses in patients with HFS, while patients aged 70 and above showed a decreased risk. These findings may assist clinician to choose optimal treatment at an early stage.

Operando Mobile Catalysis for Reverse Water Gas Shift Reaction.

Metal atoms on the support serve as active sites for many heterogeneous catalysts. However, the active metal sites on the support are conventionally described as static, and the intermediates adsorbed on the support far away from the active metal sites cannot be transformed. Herein, we report the first example of operando mobile catalysis to promote catalytic efficiency by enhancing the collision probability between active sites and reactants or reaction intermediates. Specifically, ligand-coordinated Pt single atoms (isolated MeCpPt- species) are bonded on CeO2 and transformed into mobile MeCpPt(H)CO complexes during the reverse water gas shift reaction for operando mobile catalysis. This strategy enables the conversion of inert carbonate intermediates on the CeO2 support. A turnover frequency (TOF) of 6358 mol CO2 molPt -1 ⋅ h-1 and 99 % CO selectivity at 300 °C is obtained for reverse water gas shift reaction, dramatically higher than those of Pt catalysts reported in the literature. Operando mobile catalysis presents a promising strategy for designing high-efficiency heterogeneous catalysts for various chemical reactions and applications.

NK-derived exosome miR-1249-3p inhibits Mycobacterium tuberculosis survival in macrophages by targeting SKOR1.

Murine Natural Killer cells were cultivated in vitro to isolate NK-derived exosomes. Subsequent quantification via qPCR confirmed enrichment of miR-1249-3p. Ana-1 murine macrophages were cultured in vitro and subsequently inoculated with Mycobacterium tuberculosis (MTB) strain H37Rv. NK-exo and NK-exo miR-1249-3p were separately applied to the infection model, followed by immunological assays conducted post-48-hour co-culture. Western blot analyses corroborated that NK-exo exhibited exosomal marker proteins Granzyme A (GzmA), Granzyme B (GzmB), and Perforin (PFN), alongside a notable enrichment of miR-1249-3p. Functionally, NK-exo augmented the expression levels of Caspase-9,-8, and -3, as well as PARP, while attenuating the expression of NLRP3, ASC, and Cleaved-Caspase-1. Furthermore, qPCR demonstrated an up-regulation of Caspase-9, -8, and -3, along with pro-apoptotic factors Bax and Bid, and a concomitant down-regulation of the anti-apoptotic factor Bcl-2. The expression levels of inflammatory markers ASC, NLRP3, Cleaved-Caspase-1, and IL-1ß were concomitantly decreased. ELISA findings indicated diminished levels of TNF-α and ROS secretion. NK-exo miR-1249-3p specifically targeted and attenuated the expression of SKOR-1, engendering up-regulation of apoptosis-associated proteins and down-regulation of inflammation-related proteins, consequently affecting cellular fate.Our empirical evidence substantiates that NK-exo induces macrophage apoptosis, thereby mitigating MTB survival. Furthermore, NK-exo miR-1249-3p directly targets and inhibits SKOR-1 expression, leading to macrophage apoptosis and consequently hampering the proliferation of MTB. The data implicate the potential therapeutic relevance of NK-exo and miR-1249-3p in managing drug-resistant tuberculosis.

Ready-to-use interactive dual-readout differential lateral flow biosensor for two genotypes of human papillomavirus.

Ready-to-use in vitro diagnosis of multiple genotypes is vital for the prevention and treatment of cervical cancer. Herein, a paper-film-based interactive dual readout differential lateral flow biosensor is proposed to simultaneously assay two high-risk types of human papillomavirus (HPV) within the body-fluid. The CuCo2S4/ZnIn2S4 heterostructure is fabricated on the paper-film compound chip with high thermostability, and surface sulfur vacancy is introduced by mild annealing treatment to endow unexceptionable photoexcitation activity, such structure can be served as an initial energy harvester and converter. With the assistance of differential channels, the dual-target-propelled self-assembly of annular DNA and the cleavage activity of CRISPR-Cas12a are stepwise activated by sequential solution transfer. Accordingly, the input and release of polydopamine-coated gold nanoparticles with photothermal/photoelectric characteristic were implemented. The fabricated biosensor not only realized intelligent thermal-response without large instruments, but also actuated dynamic interfacial charge separation and transfer kinetics to further transmit photoelectric-signal, resulting in desirable interactive dual-signal with low limit-of-detection (0.21 pM for HPV-18 and 42.92 pM for HPV-16). Thanks to the sophisticated design of differential lateral flow paper-film compound chip and interactive dual-signal amplification strategy, sensitive detection of two HPV genotypes is realized, which provides a promising candidate for home medical intelligent diagnosis.

Protective Effect of Rifampicin Loaded by HPMA-PLA Nanopolymer on Macrophages Infected with Mycobacterium Tuberculosis.

PURPOSE: This research was designed to investigate the protective effect of rifampicin (RIF) loaded by N-(2-hydroxypropyl) methylacrylamide- (HPMA-) polylactic acid (PLA) nanopolymer on macrophages infected with Mycobacterium tuberculosis (MTB). METHODS: We first induced H37Rv to infect macrophages to build a cell model. Then, the HPMA-PLA nanopolymer loaded with RIF was prepared to treat MTB-infected macrophages. The macrophage activity was tested by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the nitric oxide (NO) in cells was measured through Griess reagent, and the bacterial activity of MTB was observed via the colony-forming unit (CFU) assay. The inflammation-related factors in cells were detected via the enzyme-linked immunosorbent assay (ELISA), the apoptosis of macrophages was examined via flow cytometry, and the expression of apoptosis-related proteins was determined by western blot (WB). RESULTS: HPMA-PLA had no obvious toxicity to macrophages. The expression of NO and inflammatory factors in macrophages infected with MTB increased significantly, but the apoptosis rate was not significantly different from that of uninfected cells. However, after treatment with HPMA-PLA-RIF or free RIF, the inflammatory reaction of infected cells was inhibited, the expression of NO was decreased, the apoptosis rate was increased, and the bacterial activity in cells was decreased, with statistically significant differences; moreover, HPMA-PLA-RIF was more effective than free RIF. CONCLUSIONS: HPMA-PLA-RIF has a high protective effect on macrophages infected with MTB, with high safety. Its protective mechanism is at least partly through inhibiting the production of NO and inflammatory response, which can inhibit bacterial activity and induce cell apoptosis.

DA-6 improves sunflower seed vigor under Al3+ stress by regulating Al3+ balance and ethylene metabolic.

Aluminum (Al3+) stress restricts plant seed germination and seedling growth seriously. Here, the sunflower "S175″ variety was used to explore the technique of improving seed vigor under Al3+ stress and investigate the effect of diethyl aminoethyl hexanoate (DA-6) on physiological characteristics in sunflower seeds during germination under Al3+ stress. The results showed that 3.0 mmol·L-1 Al3+ treatment significantly suppressed the sunflower seed germination and seedling growth. Al3+ stress significantly increased Al3+ content and secretion rates of citric and malic acids in sunflower seeds during germination. Besides, endogenous ethylene content was increased in Al3+-treated seeds. DA-6 serves as a positive signal to regulate the sunflower seed germination under Al3+ stress. Moreover, DA-6 enhanced the activities of malic dehydrogenase, citrate synthase, and isocitrate dehydrogenase, up-regulated the expressions of organic acid transport-related genes (ALMT and MATE), resulting in reduced accumulation of Al3+. Furthermore, exogenous DA-6 mitigated excessive accumulation of ethylene by decreasing the 1-aminocyclopropane-1-dihydrodipicolinate synthase activity and related-gene expression. However, DA-6 treatment had no effect on abscisic acid or gibberellin metabolism in sunflower seeds under Al3+ stress. These results confirmed that DA-6 application enhanced the germination capacity through induction of the synthesis and transport of malic and citric acids, and suppression of the excessive accumulation of endogenous ethylene, thus contributing to alleviate Al3+ toxicity in sunflower seeds.

Effect and Mechanism of Mycobacterium tuberculosis Lipoprotein LpqH in NLRP3 Inflammasome Activation in Mouse Ana-1 Macrophage.

The study is aimed at investigating the role and mechanism of LpqH of Mycobacterium tuberculosis in the activation of NLRP3 inflammasome in mouse Ana-1 macrophages. ExPASy-ProtParam, PHYRE2, ABCpred, and SYFPEITHI were used to predict and analyze the physicochemical properties, protein structure, and B cell/T cell-associated epitopes of LpqH protein. The recombinant LpqH protein was purified, and its immunoreactivity was analyzed with western blot. The LPS-treated mouse Ana-1 macrophages were incubated with purified LpqH protein directly. The expression of NLRP3, ASC, and caspase-1 protein was detected by western blot. The secretion of IL-1ß was detected by ELISA, and LDH was detected by a kit. Cell death was detected by flow cytometry. LpqH consisted of 159 amino acids and was a hydrophobic protein with stable properties. Its secondary structure contained 47% random coils, 53% ß-sheets, and 3% α-helix. The tertiary structure showed a relatively loose spatial conformation. Additionally, it had 8 B cell epitopes (score > 0.8) and 10 CTL cell epitopes (score ≥ 20). The recombinant LpqH, which had strong immunoreactivity, significantly increased the levels of NLRP3, ASC, and caspase-1 p20 (P < 0.01) and promoted the secretion of IL-1ß by the cells (P < 0.01). In addition, high concentration of KCl significantly inhibited the effect of LpqH on mouse Ana-1 macrophages and reduced the expression of NLRP3, ASC, and caspase-1 p20 (P < 0.01). However, there was no significant change in LDH (P > 0.05). Meanwhile, LpqH protein did not cause additional cell death (P > 0.05). LpqH protein has good immunogenicity and can activate the NLRP3 inflammasome through the potassium efflux pathway without causing cell death.

DZNep inhibits the proliferation of colon cancer HCT116 cells by inducing senescence and apoptosis.

EZH2 is over-expressed in human colon cancer and is closely associated with tumor proliferation, metastasis and poor prognosis. Targeting and inhibiting EZH2 may be an effective therapeutic strategy for colon cancer. 3-Deazaneplanocin A (DZNep), as an EZH2 inhibitor, can suppress cancer cell growth. However, the anti-cancer role of DZNep in colon cancer cells has been rarely studied. In this study, we demonstrate that DZNep can inhibit the growth and survival of colon cancer HCT116 cells by inducing cellular senescence and apoptosis. The study provides a novel view of anti-cancer mechanisms of DZNep in human colon cancer cells.

Multiply Confined Nickel Nanocatalysts Produced by Atomic Layer Deposition for Hydrogenation Reactions.

To design highly efficient catalysts, new concepts for optimizing the metal-support interactions are desirable. Here we introduce a facile and general template approach assisted by atomic layer deposition (ALD), to fabricate a multiply confined Ni-based nanocatalyst. The Ni nanoparticles are not only confined in Al2 O3 nanotubes, but also embedded in the cavities of Al2 O3 interior wall. The cavities create more Ni-Al2 O3 interfacial sites, which facilitate hydrogenation reactions. The nanotubes inhibit the leaching and detachment of Ni nanoparticles. Compared with the Ni-based catalyst supported on the outer surface of Al2 O3 nanotubes, the multiply confined catalyst shows a striking improvement of catalytic activity and stability in hydrogenation reactions. Our ALD-assisted template method is general and can be extended for other multiply confined nanoreactors, which may have potential applications in many heterogeneous reactions.

Environmental level of cadmium exposure stimulates osteoclasts formation in male rats.

Low level of cadmium (Cd) exposure may enhance osteoclasts formation in vitro. The aim of the study was to observe the effects of Cd on osteoclasts formation in vivo. Sprague-Dawley male rats were divided into 4 groups which were given Cd via drinking water at concentrations of 0, 2, 10 and 50 mg/L for 12 weeks. At the 12th week, urine samples were collected from all of the rats. All rats were then sacrificed and the blood was collected for biomarkers assay. Bone tissues were dissected for mineral density determinations, histological investigation, tartrate resistant acid phosphatase staining and immunohistochemical staining. The bone mineral density and bone microstructure index of rats treated with 50mg Cd/L were obviously lower than in control rats. Histochemical investigation showed that Cd could induce osteoclasts formation in a dose-dependent manner. Tartrate resistant acid phosphatase 5b levels in rats treated with Cd were higher than the control. Immunohistochemical investigation showed that Cd could enhance receptor-activated nuclear factor kappa B ligand expression (RANKL) and inhibit osteoprotegerin (OPG) expression. Our study evidences in vivo that excessive bone resorption mediated via osteoclasts is an important way for Cd toxic effects on bone and OPG/RANKL may play an important role.

Preventive Effects of a Natural Anti-Inflammatory Agent, Astragaloside IV, on Ischemic Acute Kidney Injury in Rats.

This study investigated the anti-inflammatory effects of astragaloside IV(AS-IV) on ischemia/reperfusion (IR) induced acute kidney injury (AKI) in rats. Experimental model of ischemic AKI was induced in rats by bilateral renal artery clamp for 45 min followed by reperfusion of 12 h and 24 h, respectively. AS-IV was orally administered once a day to rats at 10 and 20 mg·kg(-1)·d(-1) for 7 days prior to ischemia. AS-IV pretreatment significantly decreased serum urea, creatinine, and cystatin C levels at 12 h and 24 h of reperfusion in AKI rats. AS-IV pretreatment also ameliorated tubular damage and suppressed the phosphorylation of p65 subunit of NF- κ B in AKI rats. Moreover, NF- κ B and MPO activity as well as serum and tissue levels of TNF- α , MCP-1, and ICAM-1 were elevated in AKI rats. All of these abnormalities were prevented by AS-IV. Furthermore, AS-IV downregulated the mRNA expression of NF- κ B, TNF- α , MCP-1, and ICAM-1 in AKI rats. These results suggest that AS-IV might be developed as a novel therapeutic approach to prevent ischemic AKI through inhibition of NF- κ B mediated inflammatory genes expression.

Therapeutic effect of forest bathing on human hypertension in the elderly.

OBJECTIVE: To provide scientific evidence supporting the efficacy of forest bathing as a natural therapy for human hypertension. METHODS: Twenty-four elderly patients with essential hypertension were randomly divided into two groups of 12. One group was sent to a broad-leaved evergreen forest to experience a 7-day/7-night trip, and the other was sent to a city area in Hangzhou for control. Blood pressure indicators, cardiovascular disease-related pathological factors including endothelin-1, homocysteine, renin, angiotensinogen, angiotensin II, angiotensin II type 1 receptor, angiotensin II type 2 receptor as well as inflammatory cytokines interleukin-6 and tumor necrosis factor α were detected. Meanwhile, profile of mood states (POMS) evaluation was used to assess the change of mood state of subjects. In addition, the air quality in the two experimental sites was monitored during the 7-day duration, simultaneously. RESULTS: The baselines of the indicators of the subjects were not significantly different. Little alteration in the detected indicators in the city group was observed after the experiment. While subjects exposed to the forest environment showed a significant reduction in blood pressure in comparison to that of the city group. The values for the bio-indicators in subjects exposed to the forest environment were also lower than those in the urban control group and the baseline levels of themselves. POMS evaluation showed that the scores in the negative subscales were lowered after exposure to the forest environment. Besides, the air quality in the forest environment was much better than that of the urban area evidenced by the quantitative detection of negative ions and PM10 (particulate matter < 10 µm in aerodynamic diameter). CONCLUSION: Our results provided direct evidence that forest bathing has therapeutic effects on human hypertension and induces inhibition of the renin-angiotensin system and inflammation, and thus inspiring its preventive efficacy against cardiovascular disorders.

[Estimation of spike wave reduction in electrocorticography for predicting the outcomes of epilepsy surgery].

OBJECTIVE: To investigate spike wave reduction in electrocorticography (EcoG) monitoring for evaluating the outcomes of epilepsy surgery. METHODS: The epileptogenesis lesions in the target cortex was localized accurately using an EcoG monitoring system in 20 surgical patients with intractable EP. The spike numbers within 60 s were recorded before and after surgical resection of the epileptogenic focus. In cases where the spike number within 60 s was reduced by over 80% after the resection, the surgery was terminated, otherwise extended lesion resection, corpus callosotomy or multiple subpial transection (MST) was carried out with ECoG monitoring, and the spike number within 60 s was recorded. Antiepileptic drugs were routinely prescribed after the operations. RESULTS: Twelve patients exhibited a spike wave reduction by over 80% after resection or extended resection of the lesions, including 4 with cavernomas in the nonfunctional area, who showed a spike wave reduction by over 80% after extended resection of the cortex around the tumor. The reduction was still less than 80% in 4 patients with hippocampal sclerosis and 3 with neurogliocytoma in the functional area after the operations. According to the Engel assessments, 13 cases were in level I, 3 cases in level II, 1 in level III, and 3 in level IV. Seventeen patients responded favorably to the treatment, with a total effective rate of 85%. CONCLUSION: For extra-temporal lobe epilepsy, a postoperative spike wave reduction beyond 80% indicate favorable outcome of the surgery, otherwise poor prognosis is expected. But in cases of temporal lobe epilepsy, no direct association is found between spike wave reduction and the prognosis of the patients.

Molecular dynamics simulation of benzene-propene-cumene mixtures in different phases.

Molecular dynamics simulations have been performed to study the microscopic configuration and dynamic behavior of mixtures of benzene, propene, and cumene for the cumene synthesis process. The comparisons have been made for the intermolecular radial distribution functions of the binary and ternary mixtures at the conditions that are near, below, and above their respective critical points. The results have shown that in both binary and ternary mixtures propene molecules have a small tendency to cluster in the liquid state, but at supercritical conditions they tend to be uniformly distributed. Contrary to propene, cumene molecules have a tendency to cluster in ternary mixtures. A moderate local density augmentation is also found in the benzene-propene binary supercritical fluid. The excess functions for benzene-propene binary mixtures have shown that there exists an enhancement of the potential energy when benzene mixes with propene. This enhancement provides a rational explanation for the experimental critical properties, which exhibit the behavior of the nonmonotonous dependence of critical pressure on compositions.

Epidermal growth factor receptor-regulated miR-125a-5p--a metastatic inhibitor of lung cancer.

Both the epidermal growth factor receptor signaling pathway and microRNA (miRNA) play an important role in lung cancer development and progression. To address the potential role of miRNA in epidermal growth factor receptor signaling, we identified miR-125a-5p as a downstream target, using an miRNA array. We further demonstrated that miR-125a-5p inhibited migration and invasion of lung cancer cells. Moreover, miR-125a-5p regulated the expression of several downstream genes of epidermal growth factor receptor signaling. Importantly, examination of lung cancer samples revealed a significant correlation of miR-125a-5p repression with lung carcinogenesis. Taken together, our results provide compelling evidence that miR-125a-5p, an epidermal growth factor-signaling-regulated miRNA, may function as a metastatic suppressor.

MicroRNA-183 regulates Ezrin expression in lung cancer cells.

Lung cancer is the leading cause of cancer death. However, the mechanism of lung cancer relapse and metastasis has been poorly elucidated. Recent researches have addressed the role of MicroRNAs (miRNAs) in mediating tumor metastasis. In the present study, we identified microRNA-183 (miR-183) as a potential metastasis-inhibitor. Expression level of miR-183 was reversely correlated with the metastatic potential of lung cancer cells. Furthermore, over-expression of miR-183 inhibited migration and invasion of lung cancer cells. Mechanistically, we identified VIL2-coding-protein Ezrin as a bona fide target of miR-183. We also found that miR-183 could regulate the expression of other genes involved in migration and invasion. Taken together, our findings demonstrated a new role and regulatory mechanism of miR-183 in controlling cancer metastasis.