Surgical outcomes of patients with genetically refractory epilepsy: A systematic review and meta-analysis.

OBJECTIVE: To summarize the surgical outcomes of genetically refractory epilepsy and identify prognostic factors for these outcomes. METHODS: A literature search of the PubMed, Web of Science, and Embase databases for relevant studies, published between January 1, 2002 and December 31, 2023, was performed using specific search terms. All studies addressing surgical outcomes and follow-up of genetically refractory epilepsy were included. All statistical analyses were performed using STATA software (StataCorp LLC, College Station, TX, USA). This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2020 (i.e., "PRISMA") reporting guidelines. RESULTS: Of the 3833 studies retrieved, 55 fulfilled the inclusion criteria. Eight studies were eligible for meta-analysis at the study level. Pooled outcomes revealed that 74 % of patients who underwent resective surgery (95 % confidence interval [CI] 0.55-0.89; z = 9.47, p < 0.05) achieved Engel I status at the last follow-up. In the study level analysis, pooled outcomes revealed that 9 % of patients who underwent vagus nerve stimulation achieved seizure-free status (95 % CI 0.00-0.31; z = 1.74, p < 0.05), and 61 % (95 % CI 0.55-0.89; z = 11.96, p < 0.05) achieved a 50 % reduction in seizure frequency at the last follow-up. Fifty-three studies comprising 249 patients were included in an individual-level analysis. Among patients who underwent lesion resection or lobectomy/multilobar resection, 65 % (100/153) achieved Engel I status at the last follow-up. Univariate analysis indicated that female sex, somatic mutations, and presenting with focal seizure symptoms were associated with better prognosis (p < 0.05). Additionally, 75 % (21/28) of patients who underwent hemispherectomy/hemispherotomy achieved Engel I status at the last follow-up. In the individual-level analysis, among patients treated with vagus nerve stimulation, 21 % (10/47) were seizure-free and 64 % (30/47) experienced >50 % reduction in seizure frequency compared with baseline. CONCLUSION: Meticulous presurgical evaluation and selection of appropriate surgical procedures can, to a certain extent, effectively control seizures. Therefore, various surgical procedures should be considered when treating patients with genetically refractory epilepsy.

[Clinical Features and Prognostic of Patients with Primary Central Nervous System Lymphoma].

OBJECTIVE: To explore the clinical features and prognosis of patients with primary central nervous system lymphoma（PCNSL）. METHODS: A retrospective analysis was performed on the relationship between clinical features, treatment regimen and prognosis in 46 newly diagnosed patients with primary central nervous system lymphoma who were diagnosed and treated in The Second Hospital of Lanzhou University from January 2015 to September 2022. Fisher's exact probability method was used to analyze the differences in clinical data of different subgroups. Kaplan-Meier survival curve was used to analyze the overall survival rate and progression-free survival rate of patients with different treatments, and the factors influencing survival were analyzed. RESULTS: Among 46 patients with PCNSL, which pathological type were diffuse large B-cell lymphoma（DLBCL）. There were 26(56.5%) cases of male and 20(43.5%) of female, with a median age of 54(17-71) years. In Hans subtypes, 14 cases (30.4%) of GCB subtype, 32 cases (69.6%) of non-GCB subtype. 32 cases (69.6%) of Ki-67≥80%. Among 36 patients who completed at least 2 cycles of treatment with follow-up data, the efficacy evaluation was as follows: overall response rate(ORR) was 63.9%, complete response(CR) rate was 47.2%, 17 cases of CR, 6 cases of PR. The 1-year progression-free survival rate and 1-year overall survival rate was 73.6% and 84.9%, respectively. The 2-year progression-free survival rate and 2-year overall survival rate was 52.2% and 68.9%, respectively. The ORR and CR rate of 17 patients treated with RMT regimen was 76.5% and 52.9% (9 cases CR and 4 cases PR), respectively. Univariate analysis of 3 groups of patients treated with RMT regimen, RM-BTKi regimen, and RM-TT regimen as first-line treament showed that deep brain infiltration was associated with adverse PFS(P =0.032), and treatment regimen was associated with adverse OS in PCNSL patients（P =0.025）. CONCLUSION: Different treatment modalities were independent prognosis predictors for OS, the deep brain infiltration of PCNSL is a poor predictive factor for PFS. Patients with relapse/refractory (R/R) PCNSL have a longer overall survival time because to the novel medication BTKi. They have strong toleration and therapeutic potential as a first-line therapy for high-risk patients.

Preparation of Luvangetin Nanoemulsions: Antimicrobial Mechanism and Role in Infected Wound Healing.

Purpose: Incorporation of luvangetin in nanoemulsions for antimicrobial and therapeutic use in infected wound healing. Patients and Methods: Luvangetin nanoemulsions were prepared by high-speed shear method and characterized based on their appearance structure, average droplet size, polydispersity index (PDI), electric potential, storage stability. Optimized formulation of luvangetin nanoemulsion by Box-Behnken design (BBD). The antimicrobial activity and antimicrobial mechanism of luvangetin nanoemulsions against common hospital pathogens, ie, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), were investigated using luvangetin nanoemulsions. The biosafety of luvangetin nanoemulsion was evaluated through cytotoxicity, apoptosis, and reactive oxygen species (ROS) assay experiments using human normal epidermal cells and endothelial cells. Finally, the effect of luvangetin nanoemulsion on healing of infected wounds was investigated in B6 mice. Results: Luvangetin nanoemulsion formulation consists of 2.5% sunflower seed oil, 10% emulsifier Span-20 and 7 minutes of shear time, and with good stability. Luvangetin nanoemulsion produces antibacterial activity against S. aureus and E. coli by disrupting the structure of bacterial cell membranes. Luvangetin nanoemulsion are biologically safe for HaCat and HUVEC. Luvangetin nanoemulsion showed good therapeutic effect on MRSA infected wounds in mice. Conclusion: For the first time, developed a new formulation called luvangetin nanoemulsion, which exhibited superior antibacterial effects against Gram-positive bacteria. Luvangetin nanoemulsion has a favorable effect in promoting infected wound healing. We have combined luvangetin, which has multiple activities, with nanoemulsions to provide a new topical fungicidal formulation, and have comprehensively evaluated its effectiveness and safety, opening up new possibilities for further applications of luvangetin.

Novel Metal-Free Synthesis of 3-Substituted Isocoumarins and Evaluation of Their Fluorescence Properties for Potential Applications.

A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible (2-carboxybenzyl)-triphenylphosphonium bromide and diverse chlorides produced various 1H-isochromen-1-one in the presence of triethylamine, employing sequential O-acylation and an intramolecular Wittig reaction of acid anhydride. Reactions using these facile conditions have exhibited high functional group tolerance and excellent yields (up to 90%). Moreover, the fluorescence properties of isocoumarin derivatives were evaluated at the theoretical and experimental levels to determine their potential application in fluorescent materials. These derivatives have good photoluminescence in THF with a large Stokes shift and an absolute fluorescence quantum yield of up to 14%.

Enhancement of Magneto-Chiral Dichroism Intensity by Chemical Design: The Key Role of Magnetic-Dipole Allowed Transitions.

Here we report on the strong magneto-chiral dichroism (MChD) detected through visible and near-infrared light absorption up to 5.0 T on {Er5Ni6} metal clusters obtained by reaction of enantiopure chiral ligands and NiII and ErIII precursors. Single-crystal diffraction analysis reveals that these compounds are 3d-4f heterometallic clusters, showing helical chirality. MChD spectroscopy reveals a high gMChD dissymmetry factor of ca. 0.24 T-1 (T = 4.0 K, B = 1.0 T) for the 4I13/2 ← 4I15/2 magnetic-dipole allowed electronic transition of the ErIII centers. This record value is 1 or 2 orders of magnitude higher than that of the d-d electronic transitions of the NiII ions and the others f-f electric-dipole induced transitions of the ErIII centers. These findings clearly show the key role that magnetic-dipole allowed transitions have in the rational design of chiral lanthanide systems showing strong MChD.

[Whole Exome Sequencing Reveals Gene Mutation Characteristics of Primary Central Nervous System Lymphoma].

OBJECTIVE: To investigate gene mutation characteristics of primary central nervous system lymphoma (PCNSL) through whole exome sequencing (WES) to 18 patients with PCNSL. METHODS: Tumor tissues from 18 patients with diffuse large B-cell lymphoma who were diagnosed with PCNSL in Department of Hematology, Lanzhou University Second Hospital from September 2018 to December 2020 and had normal immune function, no history of HIV or immunosuppressant therapy were collected. High-throughput-based WES was performed on the tumor tissues, with an average sequencing depth of >100×. After data processing and bioinformatics analysis of sequencing results, the mutation maps and mutation characteristics of 18 PCNSL patients were obtained. RESULTS: Obvious somatic mutations were detected in all 18 patients. The median number of somatic mutations was 321. Missense mutations were most prominent (accounting for about 90%), and the mutation type was dominated by C>T (50.2%), reflecting the age-related mutation pattern. Among the top 15 frequently mutated genes, PSD3, DUSP5, MAGEB16, TELO2, FMO2, TRMT13, AOC1, PIGZ, SVEP1, IP6K3, and TIAM1 were the driver genes. The enrichment results of driver gene pathways showed that RTK-RAS, Wnt, NOTCH, Hippo and Cell-Cycle pathways were significantly enriched. The tumor mutation burden was between 3.558 48/Mb and 8.780 89/Mb, and the average was 4.953 32/Mb, which was significantly higher than other cancer research cohorts in the TCGA database. CONCLUSIONS: PCNSL occurs somatic missense mutations frequently, mainly point mutations, and the mutation type is mainly C>T. The driver genes are mainly involved in RTK-RAS, Wnt, NOTCH and Hippo pathways, indicating that the above pathways may be related to the pathogenesis of PCNSL. PCNSL has a significantly high tumor mutation burden, which may explain the efficacy of PD-1 inhibitors in PCNSL.

Throat microbiota drives alterations in pulmonary alveolar microbiota in patients with septic ARDS.

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

The HPV viral regulatory mechanism of TLRs and the related treatments for HPV-associated cancers.

Infection with human papillomavirus (HPV) typically leads to cervical cancer, skin related cancers and many other tumors. HPV is mainly responsible for evading immune tumor monitoring in HPV related cancers. Toll like receptors (TLRs) are particular pattern recognition molecules. When the body is facing immune danger, it can lead to innate and direct adaptive immunity. TLR plays an important role in initiating antiviral immune responses. HPV can affect the expression level of TLR and interfere with TLR related signaling pathways, resulting in sustained viral infection and even carcinogenesis. This paper introduces the HPV virus and HPV related cancers. We discussed the present comprehension of TLR, its expression and signaling, as well as its role in HPV infection. We also provided a detailed introduction to immunotherapy methods for HPV related diseases based on TLR agonists. This will provide insights into methods that support the therapeutic method of HPV related conditions with TLR agonists.

Progress of researches on mechanisms of acupuncture therapy in the treatment of lumbar disc herniation. / é’ˆç¸æ²»ç–—è °æ¤Žé—´ç›˜çªå‡ºç—‡ä½œç”¨æœºåˆ¶ç ”ç©¶è¿›å±•.

Lumbar intervertebral disc herniation (LDH) is a common and frequently-occurring disease, which usually causes lumbar and leg pain. Studies have shown that acupuncture can improve the symptoms of LDH patients. In the present paper, we summarize the progress of researches on the mechanisms of acupuncture underlying improvement of symptoms of LDH in recent 10 years from 1) delaying the intervertibral disc degeneration (by down-regulating the expressions of matrix metalloproteinase ï¼»MMPï¼½-3 and MMP-4, up-regulating the expressions of diosaccharides and polyglycoprotein, inhibiting apoptosis and promoting mitochondrial autophagy of nucleus pulposus cells, etc.), 2) maintaining spinal column stability (by relieving rachiasmus and improving lumbar flexor and extensor muscle strength, lowering the degree of polyfidus edema and fat infiltration, and restoring the biomechanics of the spine), 3) regulating inflammation (by inhibiting the production of proinflammatory factors and increasing the production of anti-inflammatory factors, etc.), 4) regulating immune response (by promoting the activity of T cells and other immune cells, lowering serum levels of MMP-3, transforming growth factor-ß1 and prostaglandin E2, raising serum levels of IgA, IgG and IgM to improve immune function ), 5) modulating neural structure and function (by promoting myelin regeneration of sciatic nerve fibers, and reducing the edema of Schwann cells' cytoplasm and mitochondria, and improving neural ultrastructure, and sensory and motor functions of peripheral nerves, etc.), 6) relieving lumbar pain (by down-regulating expression of Ca2+/calmodulin-dependent protein kinase and activation of lumbar spinal cord glial cells, blocking nociceptive signal conduction, regulating the levels of pain-related factors, etc.), and 7) improving local microcirculation. These results may provide scientific evidence for acupuncture treatment of LDH.

Unicentric Castleman's disease in the parotid gland associated with psoriasis: a case report.

BACKGROUND: Castleman's disease is a rare lymphoproliferative disorder that is often misdiagnosed because of its untypical clinical or imaging features except for a painless mass. Besides, it is also difficult to cure Castleman's disease due to its unclear pathogenesis. CASE PRESENTATION: We present a Castleman's disease case with diagnostic significance regarding a 54-year-old Chinese male who has a painless mass in his left parotid gland for 18 months with a 30-years history of autoimmune disease psoriasis. Computed tomography scan showed a high-density nodule with clear boundaries in the left parotid and multiple enlarged lymph nodes in the left submandibular and neck region. General checkup, the extremely elevated serum interleukin-6 and lymph node biopsy in the left submandibular region gave us an initial suspicion of Castleman's disease. Then the patient underwent a left superficial parotidectomy. Based on histopathologic analysis, we made a certain diagnosis of Castleman's disease and gave corresponding treatments. In 18 months of follow-up, the patient showed no evidence of recurrence, with the level of serum interleukin-6 decreased. CONCLUSIONS: Clinicians should be aware of the possibility of Castleman's disease when faced with masses or enlarged lymph nodes in the parotid gland to avoid misdiagnosis, especially in patients with autoimmune diseases and elevated serum interleukin-6.

Endometrial Cancer Detection by DNA Methylation Analysis in Cervical Papanicolaou Brush Samples.

Background: Endometrial cancer (EC) is the leading gynecological cancer worldwide, yet current EC screening approaches are not satisfying. The purpose of this retrospective study was to evaluate the feasibility and capability of DNA methylation analysis in cervical Papanicolaou (Pap) brush samples for EC detection. Methods: We used quantitative methylation-sensitive PCR (qMS-PCR) to determine the methylation status of candidate genes in EC tissue samples, as well as cervical Pap brushes. The ability of RASSF1A and HIST1H4F to serve as diagnostic markers for EC was then examined in cervical Pap brush samples from women with endometrial lesions of varying degrees of severity. Results: Methylated RASSF1A and HIST1H4F were found in EC tissues. Further, methylation of the two genes was also observed in cervical Pap smear samples from EC patients. Methylation levels of RASSF1A and HIST1H4F increased as endometrial lesions progressed, and cervical Pap brush samples from women affected by EC exhibited significantly higher levels of methylated RASSF1A and HIST1H4F compared to noncancerous controls (P < .001). Receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses revealed RASSF1A and HIST1H4F methylation with a combined AUC of 0.938 and 0.951 for EC/pre-EC detection in cervical Pap brush samples, respectively. Conclusion: These findings demonstrate that DNA methylation analysis in cervical Pap brush samples may be helpful for EC detection, broadening the scope of the commonly used cytological screening. Our proof-of-concept study provides new insights into the field of clinical EC diagnosis.

Regulation effect of magnetic field combined with low temperature storage on postharvest quality and cell wall pectic-polysaccharide degradation of Clausena lansium (Lour.) Skeels.

This study investigated the regulation effect of magnetic field combined with low temperature storage on postharvest quality and cell wall pectic-polysaccharide degradation of wampee stored for 15 d at 4 °C and 15 °C. Results showed that magnetic field combined with low temperature storage reduced browning rate of fruit after 15 d storage, but its effect on weight loss rate and total soluble solids (TSS) did not surpass that of storage temperature. Interestingly, contents of flavonoid, total phenols and malondialdehyde (MDA) were also lowered at varying degrees by combined treatment. Furthermore, molecular weight distribution and monosaccharide compositions of cell wall pectic-polysaccharides were also affected, which resulted from the coordinated action of cell wall pectin-degrading enzymes. The activities of these enzymes during storage, including polygalacturonase (PG), pectin methylesterase (PME) and ß-galactosidase (ß-Gal) in treated wampee decreased. These findings suggested that magnetic field combined with low temperature storage was an effective technology and had great potential in preservation of postharvest wampee in future.

Integrins regulation of wound healing processes: insights for chronic skin wound therapeutics.

Integrins are heterodimers composed of non-covalently associated alpha and beta subunits that mediate the dynamic linkage between extracellular adhesion molecules and the intracellular actin cytoskeleton. Integrins are present in various tissues and organs and are involved in different physiological and pathological molecular responses in vivo. Wound healing is an important process in the recovery from traumatic diseases and consists of three overlapping phases: inflammation, proliferation, and remodeling. Integrin regulation acts throughout the wound healing process to promote wound healing. Prolonged inflammation may lead to failure of wound healing, such as wound chronicity. One of the main causes of chronic wound formation is bacterial colonization of the wound. In this review, we review the role of integrins in the regulation of wound healing processes such as angiogenesis and re-epithelialization, as well as the role of integrins in mediating bacterial infections during wound chronicity, and the challenges and prospects of integrins as therapeutic targets for infected wound healing.

One-Step Construction of 1,3,4-Oxadiazoles with Anticancer Activity from Tertiary Amines via a Sequential Copper(I)-Catalyzed Oxidative Ugi/aza-Wittig Reaction.

An unparalleled copper(I)-catalyzed synthesis of 1,3,4-oxadiazoles from tertiary amines in one step has been described. The one-pot reactions involving (N-isocyanimine)triphenylphosphorane, tertiary amines, and carboxylic acids resulted in the formation of 1,3,4-oxadiazoles in moderate to good yields through a consecutive oxidative Ugi/aza-Wittig reaction, enabling the direct functionalization of sp3 C-H bonds adjacent to the nitrogen atom. This method offered several notable advantages, including ligands-free, exceptional productivity and a high functional group tolerance. The preliminary biological evaluation demonstrated that compound 4f inhibited hepatoma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.

Phenanthrothiophene-Triazine Star-Shaped Discotic Liquid Crystals: Synthesis, Self-Assembly, and Stimuli-Responsive Fluorescence Properties.

Lipophilic biphenylthiophene- and phenanthrothiophene-triazine compounds, BPTTn and CPTTn, respectively, were prepared by a tandem procedure involving successive Suzuki-Miyaura coupling and Scholl cyclodehydrogenation reactions. These compounds display photoluminescence in solution and in thin film state, solvatochromism with increasing solvent's polarity, as well as acidochromism and metal ion recognition stimuli-responsive fluorescence. Protonation of BPTT10 and CPTT10 by trifluoroacetic acid results in fluorescence quenching, which is reversibly restored once treated with triethylamine (ON-OFF switch). DFT computational studies show that intramolecular charge transfer (ICT) phenomena occurs for both molecules, and reveal that protonation enhances the electron-withdrawing ability of the triazine core and reduces the band gap. This acidochromic behavior was applied to a prototype fluorescent anti-counterfeiting device. They also specifically recognize Fe3+ through coordination, and the recognition mechanism is closely related to the photoinduced electron transfer between Fe3+ and BPTT10/CPTT10. CPTTn self-assemble into columnar rectangular (Colrec) mesophase, which can be modulated by oleic acid via the formation of a hydrogen-bonded supramolecular liquid crystal hexagonal Colhex mesophase. Finally, CPTTn also form organic gels in alkanes at low critical gel concentration (3.0 mg/mL). Therefore, these star-shaped triazine molecules possess many interesting features and thus hold great promises for information processing, liquid crystal semiconductors and organogelators.

Assessment of isthmus filling using two obturation techniques performed by students with different levels of clinical experience.

Background/purpose: Root canal filling is a necessary skill for dental students and an important aspect of endodontic education. This study aimed to evaluate the effect of students' clinical experiences on isthmus filling using different techniques and sealers. Materials and methods: One hundred eight three-dimensional-printed resin replicas of isthmus were divided into six groups and either continuous wave of condensation (CWC) or single-cone obturation (SC) was performed. One of three sealers (AH Plus Jet®, GuttaFlow2, iRoot SP) was used together with a size-fitted gutta-percha master cone. All the obturations were completed by students with three different levels of clinical experience including senior postgraduate students (SPS), junior postgraduate students (JPS), and undergraduate students (US). The percentages of filled areas (PFA) at 2, 4, 6, and 8 mm from the apex were analyzed using a light microscope. Data were analyzed using the Mann-Whitney U test or Kruskal-Wallis 1-way ANOVA with Dunn's tests (α = 0.05). Results: The CWC group exhibited a higher PFA than the SC group (P < 0.05). The PFA was higher in the SPS group than in the JPS group or the US group with CWC (P < 0.05). The three clinical experience groups showed similar PFAs with SC (P > 0.05); however, when using SC with iRoot SP, the PFA was higher than with either of the other two sealers (P < 0.05). Conclusion: CWC was found to be technique-sensitive and required clinical training. With SC, clinical experience did not improve the quality of isthmus filling without additional training. CWC was superior to SC for type IV isthmuses. When using SC, better filling quality was obtained with a bioceramic sealer.

Role and research progress of spasmolytic polypeptide­expressing metaplasia in gastric cancer (Review).

Gastric cancer ranks as one of the most prevalent cancers worldwide. While the incidence of gastric cancer in Western countries has notably diminished over the past century, it continues to be a leading cause of cancer­related mortality on a global scale. The majority of gastric cancers in humans are attributed to chronic Helicobacter pylori infection and the progression of gastric cancer is often preceded by gastritis, atrophy, metaplasia and dysplasia. However, the precise mechanisms underlying the development of gastric cancer remain ambiguous, including the formation of gastric polyps and precancerous lesions. In humans, two types of precancerous metaplasia have been identified in relation to gastric malignancies: Intestinal metaplasia and spasmolytic polypeptide­expressing metaplasia (SPEM). The role of SPEM in the induction of gastric cancer has gained recent attention and its link with early­stage human gastric cancer is increasingly evident. To gain insight into SPEM, the present study reviewed the role and research progress of SPEM in gastric cancer.

Anti-hepatocellular carcinoma activity of Sorbaria sorbifolia by regulating VEGFR and c-Met/apoptotic pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sorbaria sorbifolia (SS) is a traditional Chinese medicine (TCM) that has been employed anti-hepatocellular carcinoma (HCC) for over 2000 years; yet, its underlying mechanism is still not fully understood. AIM OF THE STUDY: In this study, we evaluated the anti-HCC effect on the freeze-dried powder of the water extract of SS (FDSS) by inhibiting tumor-induced neovascularization, and promoting apoptosis, and elucidated the underlying mechanisms. MATERIALS AND METHODS: HCC cell lines (HepG2 and Huh7 cells) and HepG2 xenograft tumors in zebrafish were employed as in vivo and in vitro models, respectively, to evaluate the anti- HCC-indued neovascularization and apoptosis. In HCC cell lines, CCK-8 assay, wound-healing assay, transwell assay, cell circle assay, apoptosis assay, transmission electron microscopy, and co-culture assay were performed in vitro; in HepG2 xenograft tumor-zebrafish, tumor growth inhibition assay, hematoxylin and eosin (HE) staining, xenograft tumor-zebrafish apoptosis assay, and HCC-indued neovascularization assay were performed to evaluate the effect of FDSS on biological behavior of tumor, HCC-indued neovascularization, and apoptosis. The expression of VEGFR and c-Met/apoptotic pathway-related proteins was detected by western blotting analysis. Assays for c-Met and VEGFR activation were conducted to assess the impact of FDSS in either agonistic or inhibitory roles on these receptor proteins. RESULTS: The findings from our study revealed that FDSS effectively suppresses the proliferation, migration, and invasion of HepG2 and Huh7 cells, as well as inhibiting tumor growth in the HepG2 xenograft zebrafish model by downregulating the expression of p-Met and p-AKT proteins. FDSS decreased the tumor growth associated with promoting apoptosis, including arresting HepG2 and Huh7 cells cycle at G0/G1phase, increasing apoptotic cell numbers and apoptotic bodies in cancer cells, and increasing the apoptotic fluorescence of xenograft tumor zebrafish by downregulating Bcl-2 proteins and upregulating Bax, caspase-9, and caspase-3 levels. We also found that FDSS can inhibit HCC-induced neovascularization and regulate VEGFR. Using an agonist or inhibitor of c-Met and VEGFR in HepG2 cells, we discovered that FDSS can downregulate c-Met and VEGFR protein expression. CONCLUSION: FDSS exerts an anti-HCC effect by inhibiting HCC-indued neovascularization and pro-apoptosis through the inhibition of the action of VEGFR and c-Met/apoptotic pathway.

Mice with type I interferon signaling deficiency are prone to epilepsy upon HSV-1 infection.

Viral encephalitis continues to be a significant public health concern. In our previous study, we discovered a lower expression of antiviral factors, such as IFN-ß, STING and IFI16, in the brain tissues of patients with Rasmussen's encephalitis (RE), a rare chronic neurological disorder often occurred in children, characterized by unihemispheric brain atrophy. Furthermore, a higher cumulative viral score of human herpes viruses (HHVs) was also found to have a significant positive correlation with the unihemispheric atrophy in RE. Type I IFNs (IFN-I) signaling is essential for innate anti-infection response by binding to IFN-α/ß receptor (IFNAR). In this study, we infected WT mice and IFNAR-deficient A6 mice with herpes simplex virus 1 (HSV-1) via periocular injection to investigate the relationship between IFN-I signaling and HHVs-induced brain lesions. While all mice exhibited typical viral encephalitis lesions in their brains, HSV-induced epilepsy was only observed in A6 mice. The gene expression matrix, functional enrichment analysis and protein-protein interaction network revealed four gene models that were positively related with HSV-induced epilepsy. Additionally, ten key genes with the highest scores were identified. Taken together, these findings indicate that intact IFN-I signaling can effectively limit HHVs induced neural symptoms and brain lesions, thereby confirming the positive correlation between IFN-I signaling repression and brain atrophy in RE and other HHVs encephalitis.

Translucency and Strength of Lithium Disilicate for Computer-Aided Design and Manufacturing at Different Thermal Temperatures and Thicknesses: An In Vitro Study.

To manufacture dental restorations composed of lithium disilicate (LD) through the computer-aided design and manufacturing (CAD/CAM) process, thermal refinement is an essential process that can affect the optical and mechanical properties of ceramics. In this study, we aimed to evaluate the translucency and flexural strength of lithium disilicate glass-ceramic for CAD/CAM using different thermal refinement schedules and thicknesses by measuring the total transmission of light through the specimen and calculating the peak load of the specimen until fracture in a piston-on-three-ball test, respectively. The results showed that a lower translucency was exhibited in thicker specimens, and the flexural strength decreased in the order of 1.0, 0.5, and 2.0 mm (p < 0.05). The lithium disilicates thermally refined at a heat of 820 degrees were shown to have the highest biaxial flexural strength (p < 0.05). These findings suggest that it is possible to adjust transparency and strength according to the clinical situation by choosing an appropriate thickness and thermal refinement process.