High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective:To investigate the effect of GBP3 on replication of adult T-lymphocytic leukemia virus type 1(HTLV-1).Methods:Expression of GBP3 in HTLV-1-infected HeLa cell and THP1 cell was detected by Western blot.The knock-down efficiency of siRNAs targeting GBP3 in HeLa and THP1 cells was evaluated by Western blot.Effects of GBP3 overexpression or knockdown on expression of HTLV-1 proviral transcripts Tax,px,HBZ,Gag,ENV,5'UTR,and viral proteins Tax,p19 were investigated by RT-qPCR and Western blot.GTPase-defective mutant of GBP3,GBP3K51A was constructed to explore whether the effects of GBP3 on HTLV-1 infection were dependent on its GTPase activity.Results:GBP3 expression was upregulated in HTLV-1 infected HeLa and THP1 cells.GBP3 overexpression decreased expression of HTLV-1 proviral transcripts and viral proteins,whereas the knockdown of GBP3 has the opposite effects.Overexpression of GBP3K51A increased expression of HTLV-1 proviral transcripts and viral proteins.Conclusion:HTLV-1 virus infection can induce expression of GBP3;overexpression of GBP3 inhibits virus replication and may depend on GTPase.

There are complex neural mechanisms involved in speech production,and being well understood by clinicians and speech therapists can help them identify the abnormal speech and predict the severity of disorders.Dysarthria is a typical speech production problem by nerve injury,which would reduce the speech charity and intel-libility,and seriously affects patients'social communication and reduces the quality of life.The author summarizes the characteristics of dysarthria,neural pathway of normal speech production and neuromechanism of dysarthria based on the theory of motion control.The aim of this paper is to provide theoretical basis to conduct effective clini-cal assessment,management and treatment of speech disorders for clinians and speech therapists.

Objective:To observe the effect of different degrees of decentration and tilt on the optical quality of the intraocular lenses (IOLs) with different focus designs.Methods:The UV 3300 PC UV-visible spectrophotometer was employed to measure the spectral transmittance of the monofocal IOL CT ASPHINA 509M (509M), bifocal IOL AT LISA 809M (809M), and trifocal IOL AT LISA Tri 839MP (839MP) within Zeiss MICS platform with a refractive power of + 20 D. The modulation transfer function (MTF) values at a spatial frequency of 50 lp/mm along with MTF curves and United States Air Force (USAF) resolution test charts for each IOL at the focal point were measured at apertures of 3.0 mm and 4.5 mm using the in vitro optical quality testing system OptiSpheric IOL R&D under centered, decentered (0.3, 0.5, 0.7, 0.9 and 1.1 mm) and tilted (3°, 5°, 7°, 9° and 11°) conditions. Results:All three IOLs filtrated the ultraviolet (UV) spectrum below 400 nm.When each IOL was in the centered position, at the 3.0 mm aperture, the MTF values were 0.772 at the far focus of the monofocal IOL 509M, 0.467 and 0.282 at the far and near focus of the bifocal IOL 809M, and 0.416, 0.147, and 0.229 at the far, intermediate, and near focus of the trifocal IOL 839MP, respectively.Whereas at the 4.5 mm aperture, the monofocal IOL 509M MTF value at the far focus was 0.664, the bifocal IOL 809M MTF values at the far and near focus were 0.506 and 0.264, and the trifocal IOL 839MP MTF values at the far, intermediate, and near focus were 0.392, 0.107, and 0.210, respectively.Among the three centered IOLs, the 509M demonstrated the highest MTF value at the far focus, followed by the 809M and then the 839MP; at the near focus, the MTF value of the 809M surpassed that of the 839MP.For decentration and tilt, the difference in MTF values of the three IOLs at the far and near focus was consistent with the differences observed when they were centered.At the same degree of decentration and tilt, all three IOLs exhibited superior optical quality at the 3.0 mm aperture compared to the 4.5 mm aperture.The optical quality of all three IOLs exhibited an overall decline as decentration and tilt increased.All three IOLs demonstrated a decrease in optical quality at the decentration of 0.3 mm or the tilt of 5°.Conclusions:The IOLs within the Zeiss MICS platform design exhibits identical spectral transmittance and UV filtering properties.Among the three IOLs, when centered, the 509M, the 839MP, and the 809M exhibit superior optical quality at the far, intermediate, and near focal points, respectively.Under decentered and tilted conditions, the 509M and the 809M demonstrate better resistance against decentration and tilt, respectively, at both far and near focuses.Additionally, all three IOLs demonstrate better optical quality at smaller apertures, given equivalent degrees of decentration or tilt.However, the optical quality at each focal point of the three IOLs decreases compared to the centered position when subjected to a decentration of 0.3 mm or a tilt of 5°.

Objective:To observe the effect of different degrees of decentration and tilt on the optical quality of the intraocular lenses (IOLs) with different focus designs.Methods:The UV 3300 PC UV-visible spectrophotometer was employed to measure the spectral transmittance of the monofocal IOL CT ASPHINA 509M (509M), bifocal IOL AT LISA 809M (809M), and trifocal IOL AT LISA Tri 839MP (839MP) within Zeiss MICS platform with a refractive power of + 20 D. The modulation transfer function (MTF) values at a spatial frequency of 50 lp/mm along with MTF curves and United States Air Force (USAF) resolution test charts for each IOL at the focal point were measured at apertures of 3.0 mm and 4.5 mm using the in vitro optical quality testing system OptiSpheric IOL R&D under centered, decentered (0.3, 0.5, 0.7, 0.9 and 1.1 mm) and tilted (3°, 5°, 7°, 9° and 11°) conditions. Results:All three IOLs filtrated the ultraviolet (UV) spectrum below 400 nm.When each IOL was in the centered position, at the 3.0 mm aperture, the MTF values were 0.772 at the far focus of the monofocal IOL 509M, 0.467 and 0.282 at the far and near focus of the bifocal IOL 809M, and 0.416, 0.147, and 0.229 at the far, intermediate, and near focus of the trifocal IOL 839MP, respectively.Whereas at the 4.5 mm aperture, the monofocal IOL 509M MTF value at the far focus was 0.664, the bifocal IOL 809M MTF values at the far and near focus were 0.506 and 0.264, and the trifocal IOL 839MP MTF values at the far, intermediate, and near focus were 0.392, 0.107, and 0.210, respectively.Among the three centered IOLs, the 509M demonstrated the highest MTF value at the far focus, followed by the 809M and then the 839MP; at the near focus, the MTF value of the 809M surpassed that of the 839MP.For decentration and tilt, the difference in MTF values of the three IOLs at the far and near focus was consistent with the differences observed when they were centered.At the same degree of decentration and tilt, all three IOLs exhibited superior optical quality at the 3.0 mm aperture compared to the 4.5 mm aperture.The optical quality of all three IOLs exhibited an overall decline as decentration and tilt increased.All three IOLs demonstrated a decrease in optical quality at the decentration of 0.3 mm or the tilt of 5°.Conclusions:The IOLs within the Zeiss MICS platform design exhibits identical spectral transmittance and UV filtering properties.Among the three IOLs, when centered, the 509M, the 839MP, and the 809M exhibit superior optical quality at the far, intermediate, and near focal points, respectively.Under decentered and tilted conditions, the 509M and the 809M demonstrate better resistance against decentration and tilt, respectively, at both far and near focuses.Additionally, all three IOLs demonstrate better optical quality at smaller apertures, given equivalent degrees of decentration or tilt.However, the optical quality at each focal point of the three IOLs decreases compared to the centered position when subjected to a decentration of 0.3 mm or a tilt of 5°.

Objective:To investigate the effect of GBP3 on replication of adult T-lymphocytic leukemia virus type 1(HTLV-1).Methods:Expression of GBP3 in HTLV-1-infected HeLa cell and THP1 cell was detected by Western blot.The knock-down efficiency of siRNAs targeting GBP3 in HeLa and THP1 cells was evaluated by Western blot.Effects of GBP3 overexpression or knockdown on expression of HTLV-1 proviral transcripts Tax,px,HBZ,Gag,ENV,5'UTR,and viral proteins Tax,p19 were investigated by RT-qPCR and Western blot.GTPase-defective mutant of GBP3,GBP3K51A was constructed to explore whether the effects of GBP3 on HTLV-1 infection were dependent on its GTPase activity.Results:GBP3 expression was upregulated in HTLV-1 infected HeLa and THP1 cells.GBP3 overexpression decreased expression of HTLV-1 proviral transcripts and viral proteins,whereas the knockdown of GBP3 has the opposite effects.Overexpression of GBP3K51A increased expression of HTLV-1 proviral transcripts and viral proteins.Conclusion:HTLV-1 virus infection can induce expression of GBP3;overexpression of GBP3 inhibits virus replication and may depend on GTPase.

There are complex neural mechanisms involved in speech production,and being well understood by clinicians and speech therapists can help them identify the abnormal speech and predict the severity of disorders.Dysarthria is a typical speech production problem by nerve injury,which would reduce the speech charity and intel-libility,and seriously affects patients'social communication and reduces the quality of life.The author summarizes the characteristics of dysarthria,neural pathway of normal speech production and neuromechanism of dysarthria based on the theory of motion control.The aim of this paper is to provide theoretical basis to conduct effective clini-cal assessment,management and treatment of speech disorders for clinians and speech therapists.

AIM: To assess the repeatability and agreement of higher-order aberration obtained by adaptive optics visual simulator(VAO)compared with OPD-Scan Ⅲ.METHODS: A cross-sectional study was conducted from August to September 2023, including a total of 204 patients(204 eyes)with myopia whose right eyes were measured. The examinations were performed by the same skilled examiner using both devices separately. The VAO device was used to measure higher order aberrations of orders 3 to 6 at a pupil diameter of 4.5 mm, while both the VAO and OPD-Scan Ⅲ devices were utilized to measure total higher-order aberration(tHOA), spherical aberration(SA), coma aberration(Coma), and trefoil aberration(Trefoil)of the entire eye at pupil diameters ranging from 3 to 6 mm. Furthermore, the repeatability of whole eye aberration measurements obtained with the VAO device was evaluated and the agreement of the two devices was assessed.RESULTS: The whole-eye higher-order aberrations measured by VAO demonstrated excellent repeatability(0.767≤ICC≤0.941, Sw<0.01 μm, TRT<0.1 μm). There was no statistically significant difference in Coma measured by VAO or OPD-Scan Ⅲ for pupil diameters ranging from 4 to 6 mm(P>0.05), while a statistically significant difference was observed in whole-eye tHOA of other pupil diameters(all P<0.05). The agreement of aberration measurements for each order between VAO and OPD-Scan Ⅲ for 3 mm pupil diameters, SA at 4 and 5 mm pupil diameter and Coma at 4 mm pupil diameter showed a 95% limit of agreement(LoA)<0.1, indicating good agreement; however, poor agreement was found for the remaining aberration measurements at different pupil diameters, with a 95%LoA>0.1, and there were significant differences in higher-order aberrations measured by two devices under a pupil diameter of 3 mm(r=0.218-0.317, P<0.01), 4 mm(r=0.406-0.672, P<0.01), 5 mm(r=0.538-0.839, P<0.01 and r=0.030-0.109, P>0.01)and 6 mm(r=0.369-0.766, P<0.01).CONCLUSION: The VAO demonstrates favorable repeatability when assessing whole-eye higher order aberration under pupil diameters of 3-6 mm. However, there is inadequate agreement and interchangeability in whole-eye higher order aberration at 3-6 mm pupil diameter between VAO and OPD-Scan Ⅲ for clinical purposes.

Objective:To evaluate the optical performance of two aspheric intraocular lenses (IOL) AcrySof IQ SN60WF and Proming A1-UV with identical negative spherical aberration values, using the optical bench OptiSpheric IOL R&D through an in vitro study. Methods:The optical performance of + 20.0 D blue-light filtering SN60WF and monofocal high-order aspheric non blue-light filtering A1-UV IOL was evaluated through cornea models with the spherical aberration of 0 μm (ISO-1) and + 0.28 μm (ISO-2) under apertures of 3.0 mm and 4.5 mm via the optical bench OptiSpheric IOL R&D.The modulation transfer function (MTF) and USAF 1951 resolution test chart were employed to measure the IOL with centering, decentration of 0.3, 0.5, 0.7, 0.9 and 1.1 mm, as well as tilt of 3°, 5°, 7°, 9° and 11°.The spectral transmittance of IOL was measured with the UV-3300 UV-VIS spectrophotometer.Results:Compared with the A1-UV IOL, the spectral transmittance of SN60WF for blue light with wavelengths of 400-500 nm was significantly reduced, which effectively reduced the passage of blue light.At an aperture of 3.0 mm, the MTF values at 100 lp/mm spatial frequency for the centered SN60WF and A1-UV were 0.576 and 0.598 under ISO-1 corneal measurement conditions, 0.564 and 0.563 under ISO-2 conditions.At an aperture of 4.5 mm, the MTF values were 0.238 and 0.404 under ISO-1 corneal measurement conditions, and 0.438 and 0.339 under ISO-2 conditions.The MTF values of A1-UV and SN60WF at 3.0 mm aperture and 100 lp/mm spatial frequency under ISO-1 corneal measurement conditions were larger than those under ISO-2 corneal measurement conditions.Under ISO-1 corneal measurement conditions with a 3.0 mm aperture, A1-UV had a better optical quality compared to SN60WF, whereas under ISO-2 corneal measurement conditions, the optical quality of both IOLs was similar.Under the 3.0 mm aperture, the MTF values of SN60WF and A1-UV at a decentration of 0.3 mm and 100 lp/mm spatial frequency were 0.414 and 0.571 under ISO-1 corneal measurement conditions, 0.438 and 0.512 under ISO-2 corneal measurement conditions, respectively.The MTF values of SN60WF and A1-UV at a tilt of 3° were 0.522 and 0.597 under ISO-1 corneal measurement conditions, and 0.532 and 0.531 under ISO-2 corneal measurement conditions.The MTF values and USAF resolution test chart of A1-UV had no significant change between the two corneal measurement conditions.When subjected to equal degrees of decentration or tilting, except for the ISO-1 corneal measurement conditions at a 4.5 mm aperture, the MTF values of A1-UV showed a gradual decline across various spatial frequencies compared to SN60WF.With the increase in aperture size, the impact of IOL decentration or tilting on MTF values and USAF 1951 resolution test chart became more notable for A1-UV relative to SN60WF.Conclusions:The SN60WF IOL effectively filters blue light within the wavelength range of 400-500 nm.However, when both IOL experience decentration greater than 0.3 mm or tilting beyond 3°, the optical quality of the IOL will decline.A1-UV has a distinct advantage over SN60WF in terms of resistance to both decentration and tilting-induced optical performance degradation in vitro.

Objective:To explore the correlation between multidimensional nutritional evaluation indexes of folate and vitamin B 12 and mild cognitive impairment in community-dwelling older adults. Methods:In this study, cross-sectional study design was used, and the elderly people aged 60 years and above were recruited from three parallel communities in Shijiazhuang City.The survey was conducted including basic information questionnaire and semi-quantified food frequency questionnaires(FFQ)in the past year.The Montreal Cognitive Assessment Scale(MoCA)assessed the cognitive function.The subjects were divided into two groups of normal cognition and mild cognitive impairment according to the criteria categorized by education levels recommended by the 2018 China Dementia and Cognitive Impairment Diagnosis and Treatment Guidelines.Serum folate, vitamin B 12 and erythrocyte folate levels were measured by electrochemiluminescence immunoassay, serum homocysteine concentrations were measured by circulating enzyme assay, dietary folate and vitamin B 12 intake was calculated by FFQ survey and food composition tables.Logistic regression models were used to analyze the association between multidimensional nutritional indicators of folate and vitamin B 12 and mild cognitive impairment. Results:A total of 537 subjects were included in the study, involving 379(70.6%)with normal cognition and 158(29.4%)with mild cognitive impairment.Dietary vitamin B 12 intake and erythrocyte folate concentration was significantly lower in the elderly with mild cognitive impairment than in those with normal cognition[median(interguartile): 18.9(11.0, 32.9)μg/d vs.20.1(14.2, 34.8)μg/d, Z=2.010, P=0.044; median: 359.4(304.2, 413.4)μg/L vs.378.4(322.5, 433.1)μg/L, Z=2.168, P=0.031].The elderly with mild cognitive impairment had a higher prevalence of folate deficiency than those with normal cognition[17(10.8%) vs.22(5.8%), χ2=4.065, P=0.044].After adjusting for age, sex, and energy intake, the OR(95% CI)values for dietary vitamin B 12 intake and erythrocyte folate concentration in relation to mild cognitive impairment in the elderly were 0.99(0.987, 0.996)( P=0.039)and 0.98(0.974, 0.993)( P=0.021), respectively.The OR(95% CI)values for folate deficiency for mild cognitive impairment was 1.96(1.009, 3.795)( P=0.046). Conclusions:Long-term high dietary vitamin B 12 intake and better in vivo nutritional deposition of folate were negatively associated with mild cognitive impairment in community-dwelling elderly adults, whereas indicators reflecting the short-term nutritional status of folate and vitamin B 12 may be less associated with mild cognitive impairment.