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Qingshan Ma,1 Baogang Huai,2 Yuting Liu,3 Zhongyao Jia,1 Qilong Zhao1 1Department of Oncology, Linyi People’s Hospital, Linyi, Shandong 276000, People’s Republic of China; 2Department of Pulmonary Disease, Pinyi County Hospital of Traditional Chinese Medicine, Linyi, Shandong 273300, People’s Republic of China; 3University Department, Linyi People’s Hospital, Linyi, Shandong 276000, People’s Republic of ChinaCorrespondence: Qilong ZhaoDepartment of Oncology, Linyi People’s Hospital, No. 27, Jiefang Road, Linyi, Shandong 276000, People’s Republic of ChinaTel +86-539 8078518Email vgx4ru@163.comBackground: It was reported that circular RNAs (circRNAs) and microRNAs (miRNAs) were related to non-small cell lung cancer (NSCLC) development. However, the detailed mechanisms of circ_0020123 and miR-384 in NSCLC are elusive.Methods: QRT-PCR and Western blot assay were performed to detect the transcription and protein levels of genes, respectively. Then, the functional experiments, including MTT assay, flow cytometry, and transwell assay, were employed. Besides, the interaction between miR-384 and circ_0020123 or tripartite motif‑containing protein 44 (TRIM44) was predicted by starbase or targetscan, and then verified by the dual-luciferase reporter, RNA pull-down assays and RNA immunoprecipitation assay (RIP). Mouse xenograft assay was performed to evaluate the effect of circ_0020123 on tumor growth in vivo.Results: Levels of circ_0020123 and TRIM44 were enhanced, and the miR-384 level was attenuated in NSCLC tissues and cells. Circ_0020123 depletion attenuated the abilities of NSCLC cell viability, migration, invasion, and epithelial–mesenchymal transition (EMT), and induced apoptosis. Besides, circ_0020123 interacted with miR-384, and miR-384 targeted TRIM44. Circ_0020123 regulated cell progression by regulating miR-384 and subsequently mediated TRIM44 expression. Besides, circ_0020123 depletion repressed tumor growth in vivo.Conclusion: We demonstrated that circ_0020123 knockdown suppressed NSCLC cell progression by regulating the miR-384/TRIM44 axis, providing the theoretical basis for the therapy of NSCLC.Keywords: circ_0020123, miR-384, TRIM44, cell growth, NSCLC

Oxidative stress and metabolic disorders are involved in the pathogenesis of polycystic ovary syndrome (PCOS). Heme oxygenase 2 (HMOX2) plays a critical role in preserving heme metabolism as well as in modulating glycolipid metabolism, oxidative stress, and inflammation. This study examined the correlation between HMOX2 G554A (rs1051308) and A-42G (rs2270363) genetic variants with the risk of PCOS and assessed the effects of these genotypes on clinical, hormonal, metabolic, and oxidative stress indices using a case–control design that included 1014 patients with PCOS and 806 control participants. We found that the allelic and genotypic frequencies of the HMOX2 G554A and A-42G polymorphisms were comparable between the PCOS and control groups in Chinese women (P > 0.05). Nevertheless, it was discovered that patients with the AA or AG genotype of A-42G polymorphism had notably elevated levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo)B, and/or apoB/apoA1 ratio than those with the GG genotypes (P < 0.05). Patients with the GG or AG genotype of G554A polymorphism had elevated serum levels of LH, FSH, E2, LH/FSH ratio, TC, HDL-C, LDL-C, apoB, and/or apoB/apoA1 ratio and lower 2-h glucose concentration compared with those with the AA genotype (P < 0.05). Our findings indicate a potential association between the genetic variants and endocrine abnormalities in the reproductive system and metabolic irregularities in glycolipid levels in patients, thus suggesting their potential role in the pathogenesis of PCOS.

ABSTRACTLymphangiogenesis plays pivotal roles in diverse physiological and pathological conditions. Steady direct-current electric fields (DC EFs) induce vascular endothelial behaviors related to angiogenesis have been observed. This study investigated the effects of DC EFs on the lymphangiogenic response of lymphatic endothelial cells (LECs). We demonstrated that EFs stimulation induced directional migration, reorientation, and elongation of human LECs in culture. These lymphangiogenic responses required VEGF receptor 3 (VEGFR-3) activation and were mediated through the PI3K-Akt, Erk1/2, and p38 MAPK signaling pathways in relation to the reorganization of the actin cytoskeleton. Our results indicate that endogenous EFs may play a role in lymphangiogenesis in vivo, and VEGFR-3 signaling activation may be involved in the cellular function of LECs driven by EFs.

Abstract Background Childbearing in women with advanced maternal age (AMA) has increased the need for artificial reproductive technology (ART). ART and oxidative stress are associated with many pregnancy complications. Paraoxonase (PON) 1 is one of the key components responsible for antioxidative activity in high-density lipoprotein (HDL). This study aimed to investigate the longitudinal changes of oxidative stress and PON1 lactonase activity and status in older women undergoing ART. Methods This prospective nested case-control study included 129 control and 64 ART women. Blood samples were obtained respectively at different stages of pregnancy. PON1 level and lactonase activity were assessed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL) as a substrate, respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (HCY), PON1 C-108T and Q192R genetic polymorphisms, and metabolic parameters were analyzed. Results Lactonase activity and level of PON1 gradually decreased with pregnancy progression, while glycolipid metabolism parameters and TAC levels increased with pregnancy progression or significantly raised during the 2nd and 3rd trimesters, and NLA of PON1, TOS, OSI, MDA, and HCY significantly increased before delivery in the ART and control groups. Compared with the control women, the ART women had substantially higher or relatively high lactonase activity and NLA of PON1 and TAC during pregnancy; higher triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, atherogenic index, apolipoprotein (apo) B, and apoB/apoA1 ratio in the 1st trimester; and higher fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, and TG levels before delivery. No significant differences were found in the frequencies of PON1 C-108T and Q192R genotypes and alleles between the ART and control groups. Conclusions Women with AMA undergoing ART had higher TAC, PON1 lactonase activity, and PON1 NLA than control women, suggesting increased compensatory antioxidant capacity in ART women, thus showing higher sensitivity to oxidative stress-related injury and diseases.

Abstract Background Cytochrome P450 2E1 (CYP2E1) plays a key role in the metabolism of xenobiotic and endogenous low-molecular-weight compounds. This study aimed to determine if the genetic variations of 96-bp insertion/deletion (I/D) and C-1054T (rs2031920) in CYP2E1 were associated with the risk of gestational diabetes mellitus (GDM). Methods CYP2E1 polymorphisms were genotyped in a case-control study of 1,134 women with uncomplicated pregnancies and 723 women with GDM. The effects of genotype on the clinical, metabolic, and oxidative stress indices were assessed. Results The CYP2E1 C-1054T variant was associated with an increased risk of GDM based on the genotype, recessive, dominant, and allele genetic models (P

Oxidative stress plays an important role in the pathophysiology of gestational diabetes mellitus (GDM). We investigated the relationship between NADPH oxidase p22phox subunit (CYBA) C242T (rs4673) and myeloperoxidase (MPO) G-463A (rs2333227) genetic variants and GDM in 719 patients with GDM and 1205 control women. Clinical, metabolic, and oxidative stress parameters were analyzed. We found that frequencies of the A allele (15.6% vs 12.3%) and GA + AA genotype (28.5% vs 23.2%) of the MPO G-463A variation were significantly higher in patients with GDM than in the control women (OR = 1.318, 95% CI: 1.068–1.625, P = 0.010 for the dominant model; OR = 1.999, 95% CI: 1.040–3.843, P = 0.034 for the recessive model; OR = 1.320, 95% CI: 1.095–1.591, P = 0.004 for the allele model). Genotype GA + AA remained a significant predictor of GDM in a logistic regression model including age and BMI at delivery (OR = 1.282, 95% CI: 1.037‒1.583, P = 0.021). Furthermore, the ‒463A allele was associated with higher TG and the 242T allele was related to higher pre-pregnancy BMI and oxidative stress index in all subjects (P < 0.05). The 242T allele was also associated with higher homeostatic model assessment of insulin resistance but lower serum total antioxidant capacity in patients with GDM (P < 0.05). We conclude that the MPO G-463A, but not the CYBA C242T, genetic variation is associated with an increased risk of GDM in Chinese women. These two genetic polymorphisms may be linked to obesity, dyslipidemia, insulin resistance, and oxidative stress.

BackgroundATP-binding cassette transporter A1 (ABCA1) has important roles in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport, and is implicated in lipid-related disorders. Genetic variants are involved in the pathogenesis of gestational diabetes mellitus (GDM). The objective of this study was to investigate the association of rs2230806 (R219K), a single nucleotide polymorphism (SNP) in the lipid-related gene, with the risk of GDM and related traits.MethodsThe SNP, rs2230806, was genotyped, and clinical and metabolic parameters were determined in 660 GDM patients and 1,097 control subjects. Genetic associations with related traits were also analyzed.ResultsThe genotype distributions were similar in GDM patients and normal controls. However, significant differences in the variables examined in the study subjects were noted across the three genotypes. The genotype at the rs2230806 polymorphism was significantly associated with HDL-cholesterol (HDL-C) levels and atherogenic index (AI) values in GDM patients and total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels in control subjects. Subgroup analysis showed that the polymorphism was associated with diastolic blood pressure, in addition to HDL-C levels and AI, in overweight/obese GDM patients, while it was associated with TC levels, AI, pre-pregnancy body mass index (BMI), and BMI at delivery in non-obese GDM patients. In addition, this polymorphism was associated with TC, LDL-C, and apoB levels in overweight/obese control subjects.ConclusionsThe rs2230806 polymorphism in the ABCA1 gene was associated with variations in atherometabolic traits in GDM patients, with characteristics of BMI dependency, but not with GDM. Our findings highlight a link between related phenotypes in women with GDM and genetic factors.

Restoration of proximal tubular cell integrity and function after ischemic injury involves cell migration and proliferation. Endogenous fields are present during embryonic development and wound healing. Electric field (EF)-induced effects on cell migration have been observed in many cell types. This study investigated the effect of physiological direct current EF (dc EF) on the motility of renal epithelial cells. Human renal tubular epithelial (HK-2) and human-derived renal epithelial (HEK-293) cells were exposed to dc EF at physiological magnitude. Cell images were recorded and analyzed using an image analyzer. Cell lysates were used to detect protein expression by western blot. Scratch wounds were created in monolayers of HK-2 cells, and wound areas of cells were measured in response to EF exposure. Cells migrated significantly faster in the presence of an EF and toward the cathode. Application of an EF led to activation of the Erk1/2, p38 MAPK, and Akt signaling pathways. Pharmacological inhibition of Erk1/2, p38 MAPK, and Akt impaired EF-induced migratory responses, such as motility rate and directedness. In addition, exposure of the monolayers to EF enhanced EF-induced HK-2 wound healing. Our results suggest that EFs augment the rate of single renal epithelium migration and induce cell cathodal migration through activation of Erk1/2, p38 MAPK, and Akt signaling. Moreover, exposure of the renal epithelium to EF facilitated closure of in vitro small wounds by enhancing cell migration.

BackgroundGALNT2 is a GalNAc transferase that regulates serum lipid fractions, insulin signaling, and lipogenesis. Genetic variants are implicated in the pathogenesis of gestational diabetes mellitus (GDM). The objective of this study was to investigate the association of GALNT2 rs2144300 and rs4846914 single nucleotide polymorphisms (SNPs) with the risk of GDM and related traits.MethodsTwo SNPs were genotyped, and clinical and metabolic parameters were determined in 461 GDM patients and 626 control subjects. Genetic associations with related traits were also analyzed.ResultsThe genotype distributions of the two SNPs in GDM patients were similar to those in normal controls. However, significant differences were noted across the three groups of genotypes with respect to the examined variables in subjects in a BMI-dependent manner. The rs4846914 and rs2144300 SNPs of GALNT2 were significantly associated with systolic blood pressure and/or diastolic blood pressure levels in nonobese GDM patients and atherogenic index (AI) in overweight/obese GDM patients. The rs4846914 SNP was also associated with fetal growth in overweight/obese GDM patients, and apo A1 and pregnancy weight gain in overweight/obese control women (all P

Abstract Background Elevated serum levels of apolipoprotein (apo) C1 may be an early protein marker of metabolic abnormality in women with polycystic ovary syndrome (PCOS). It is not clear, however, whether there are any relationships between the apoC1 rs4420638A/G and -317deletion (H1)/insertion (H2) polymorphisms and PCOS. We investigated the relationship between these two variants and the risk of PCOS, evaluated the genotypic effects on clinical, hormonal and metabolic indexes and plasma platelet-activating factor acetylhydrolase (PAF-AH) activity, and defined the association of apoC1 gene variants with apoE ε2/ε3/ε4 polymorphisms. Methods This is a cross-sectional study of 877 women with PCOS and 761 controls. The apoC1 rs4420638A/G genotype was determined by a Taqman real-time PCR allelic discrimination assay. The apoC1–317H1/H2 and apoE ε2/ε3/ε4 genotypes were measured using PCR and restriction fragment length polymorphism analysis. The clinical, hormonal and metabolic parameters and PAF-AH activity were measured. Results The frequencies of apoC1 rs4420638A/G and -317H1/H2 genotypes and alleles were similar between PCOS and control groups (P > 0.05). However, the rs4420638 G allele was related to increased serum luteinizing hormone, cholesterol and apoB levels, and the ratio of apoB to apoA1 (P

Graphite oxide (GO) and amine surfactant intercalated graphite oxide (GOS) filled maleated polypropylene (PPgMA) nanocomposites were prepared directly by solution blending. In this study, the effects of the surfactant intercalation on the crystalline structure, thermo-mechanical, and dielectric properties of PPgMA/GO and GOS composites are reported. Wide-angle X-ray diffraction exhibited a lower intensity diffraction peak of the monoclinic (α) phase of PPgMA for PPgMA/GOS composites compared with the unfilled sample. Differential scanning calorimetry exhibited a single characteristic melting peak of monoclinic (α) crystalline phase. The incorporation of GOS hardly showed any change in T m. However, the significant decrease in the melting enthalpy of PPgMA/GOS composite, which was lower than that of GO filled PPgMA, demonstrated the high degree of dispersion of the GOS flakes in the PPgMA matrix. Dynamical mechanical analysis indicated that incorporation of GO or GOS into PPgMA increased both the storage modulus and the glass transition temperature, due to the hydrogen bonding between GO and the maleic anhydride group of PPgMA. Dielectric analyzer showed significant increase in both dielectric permittivity and dielectric loss at high temperature regimes in the GOS nanocomposites. The finely dispersed GOS in the PPgMA matrix manifested the interfacial polarization, which gave rise to much greater ε′ and ε″ than that of PPgMA/GO hybrid. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 [ABSTRACT FROM AUTHOR]

Background. Paraoxonase 1 (PON1) is a calcium-dependent multifunctional enzyme that binds to high-density lipoproteins. The physiological function of PON1 is related to its lactonase activity. However, this activity has not been analyzed in women with gestational diabetes mellitus (GDM). The present study investigated the lactonase activities and status of PON1 and their association with PON1 genetic variants and oxidative stress indices in Chinese women with GDM. Methods. This is a case-control study of 347 women with GDM and 288 women with uncomplicated pregnancies. PON1 levels and lactonase activities were analyzed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL), respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC) levels, and PON1 genetic polymorphisms were also analyzed. Results. PON1 lactonase activity and levels of TOS, TAC, and MDA were higher in the GDM women compared with the control women. The PON1 -108C→T genetic variation decreased the levels and lactonase activities of PON1 in a genotype-dependent manner in the patient and control groups. GDM patients with the PON1 -108TT genotype displayed lower NLA than those with the -108CC or -108CT genotype. GDM patients with the RR genotype of PON1 192Q/R polymorphism had significantly lower PON1 lactonase activities and NLA and tended to have decreased PON1 levels compared with those with the QQ or QR genotype. Multivariable regression analysis revealed that the PON1 -108C/T or 192Q/R variations, apolipoprotein (apo) A1, apoB, TAC, MDA, or age was significant predictors of the levels, lactonase activities, or NLA of PON1. Conclusions. The lactonase activities of PON1 are increased in women with GDM. PON1 genetic variants, increased oxidative stress, and abnormalities in lipoproteins may be associated with these changes.

Background: Oxidative stress plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). Glutathione peroxidase 1 (GPx1) and catalase (CAT) are the major intracellular antioxidant enzymes that can detoxify hydrogen peroxide into water, preventing cellular injury from reactive oxygen species. The aim of the present study was to investigate the association of GPx1 P198L (Pro198Leu, C559T, rs1050450) and CAT C-262T (rs1001179) genetic polymorphisms with the risk of PCOS and evaluate the effects of the genotypes on clinical, hormonal, metabolic and oxidative stress parameters in Chinese women.Methods: This is a case-control study of 654 patients with PCOS and 535 controls. The GPx1 P198L, CAT C-262T, and superoxide dismutase 2 (SOD2) A16V genotypes were determined by polymerase chain reaction amplification and restriction analysis. Clinical, hormonal, metabolic and oxidative stress parameters were also analyzed.Results: The frequencies of the PL + LL genotype (14.1 vs. 8.4%) and L allele (7.3 vs. 4.4%) of GPx1 P198L polymorphism were significantly higher in patients with PCOS than in control subjects. Genotype (PL + LL) remained a significant predictor for PCOS in prognostic models including age, body mass index (BMI), insulin resistance index, total cholesterol, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol as covariates (OR = 2.105, 95%CI: 1.330–3.331, P = 0.001). Patients carrying the L allele had relatively high average ovarian volume, waist circumference, and malondialdehyde levels (P < 0.07) compared with patients with the PP genotype. We also demonstrated that the subjects with both GPx1 L and SOD2 A alleles further increase the risk of PCOS compared with the individuals carrying the PP/VV genotype after adjusting for age and BMI (OR = 5.774, 95%CI: 2.243–14.863, P < 0.001). However, no significant differences were observed in the frequencies of the CAT C-262T genotypes and alleles between PCOS and control groups.Conclusions: The GPx1 P198L, but not CAT C-262T, genetic polymorphism is associated with the risk of PCOS in Chinese women.

Electrical stimulation induces significant neovessel formation in vivo. We have shown that electrical stimulation of endothelial cells functions as an important contributor to angiogenesis in monolayer culture. Because angiogenesis occurs in a three-dimensional (3D) environment, in this study we investigated the effects of a direct current (DC) electrical field (EF) on endothelial neovessel formation in 3D culture. There was a significant increase in tube formation when endothelial cells were stimulated with EF for 4 h. The lengths of the tube-like structures were augmented further by the continued EF exposure. The lengths of the tubes also increased dose-dependently in the EF-treated cultures in the field strengths of 50 mV/mm∼200 mV/mm for 6 h. Electrical fields of small physiological magnitude enhanced VEGF expression by endothelial cells in 3D culture. EF treatment also resulted in activation of VEGFR2, Akt, extracellular regulated kinase 1,2 (Erk1/2), as well as the c-Jun NH2-terminal kinase (JNK). The tyrosine kinase inhibitor SU1498 that blocks VEGFR2 activity exhibited a potent inhibition of tube growth, and the Akt inhibitor MK-2206 2HCl, the Erk1/2 inhibitor U0126 and the JNK inhibitor SB203580 significantly reduced EF-stimulated tubulogenesis. These results suggest the importance of the VEGFR2 signaling pathway during EF-induced angiogenesis. The results of this study provide novel evidence that endogenous EFs may promote blood vessel formation of endothelial cells by activating the VEGF receptor signaling pathway.

Moderate invasion of trophoblast cells into endometrium is essential for the placental development and normal pregnancy. Electric field (EF)-induced effects on cellular behaviors have been observed in many cell types. This study was to investigate the effect of physiological direct current EF (dc EF) on cellular responses such as elongation, orientation and motility of trophoblast cells. Immortalized first trimester extravillous trophoblast cells (HTR-8/SVneo) were exposed to the dc EF at physiological magnitude. Cell images were recorded and analyzed by image analyzer. Cell lysates were used to detect protein expression by Western blot. Cultured in the dc EFs the cells showed elongation, orientation and enhanced migration rate compared with non-EF stimulated cells at field strengths of 100 mV/mm to 200 mV/mm. EF exposure increased focal adhesion kinase (FAK) phosphorylation in a time-dependent manner and increased expression levels of MMP-2. Pharmacological inhibition of FAK impaired the EF-induced responses including motility and abrogated the elevation of MMP-2 expression. However, the expression levels of integrins like integrin α1, α5, αV and β1 were not affected by EF stimulation. Our results demonstrate the importance of FAK activation in migration/motility of trophobalst cells driven by EFs. In addition, it raises the feasibility of using applied EFs to promote placentation through effects on trophoblast cells.

Background: Secondhand smoke exposure (SHS) is a major modifiable risk factor for morbidity and premature mortality. No study has assessed inequalities by sex in SHS exposure among adolescents globally. This study aims to explore the variations in SHS exposure among adolescents globally based on sex., Methods: Most recent data from 122 countries and territories that conducted the Global Youth Tobacco Survey between 1 January 2013 and 31 December 2020, comprising 557,332 respondents aged 11-17 years, were used to assess the prevalence of SHS exposure at home, in other enclosed public places, and at school. Multivariable Poisson regression models were performed to investigate the association between sex and SHS exposure in each country., Results: A total of 195,299 (35.0 %) adolescents reported exposure to SHS at home, 256,938 (46.1 %) in other enclosed public places, 258,528 (46.4 %) at school, and 399,644 (71.7 %) in any place. There were important inequalities in the prevalence of SHS exposure between countries. More girls than boys reported exposure to SHS at home in 54 countries (vs. one country with prevalence higher in boys than girls) and in other enclosed public places in 50 countries (vs. six countries). In contrast, the prevalence of SHS exposure at school was significantly higher in boys than girls in 25 countries while the opposite was observed in 14 countries., Conclusions: These findings emphasize the disparities in SHS exposure between adolescent boys and girls and, hence, highlight the urgent need to strengthen smoke-free policies and adopt targeted policies to address them., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In medical imaging courses, due to the complexity of anatomical relationships, limited number of practical course hours and instructors, how to improve the teaching quality of practical skills and self-directed learning ability has always been a challenge for higher medical education. Artificial intelligence-assisted diagnostic (AISD) software based on volume data reconstruction (VDR) technique is gradually entering radiology. It converts two-dimensional images into three-dimensional images, and AI can assist in image diagnosis. However, the application of artificial intelligence in medical education is still in its early stages. The purpose of this study is to explore the application value of AISD software based on VDR technique in medical imaging practical teaching, and to provide a basis for improving medical imaging practical teaching., Methods: Totally 41 students majoring in clinical medicine in 2017 were enrolled as the experiment group. AISD software based on VDR was used in practical teaching of medical imaging to display 3D images and mark lesions with AISD. Then annotations were provided and diagnostic suggestions were given. Also 43 students majoring in clinical medicine from 2016 were chosen as the control group, who were taught with the conventional film and multimedia teaching methods. The exam results and evaluation scales were compared statistically between groups., Results: The total skill scores of the test group were significantly higher compared with the control group (84.51 ± 3.81 vs. 80.67 ± 5.43). The scores of computed tomography (CT) diagnosis (49.93 ± 3.59 vs. 46.60 ± 4.89) and magnetic resonance (MR) diagnosis (17.41 ± 1.00 vs. 16.93 ± 1.14) of the experiment group were both significantly higher. The scores of academic self-efficacy (82.17 ± 4.67) and self-directed learning ability (235.56 ± 13.50) of the group were significantly higher compared with the control group (78.93 ± 6.29, 226.35 ± 13.90)., Conclusions: Applying AISD software based on VDR to medical imaging practice teaching can enable students to timely obtain AI annotated lesion information and 3D images, which may help improve their image reading skills and enhance their academic self-efficacy and self-directed learning abilities., (© 2024. The Author(s).)

Aims: Sleep disturbance is a prevalent nonmotor symptom of Parkinson's disease (PD), however, assessing sleep conditions is always time-consuming and labor-intensive. In this study, we performed an automatic sleep-wake state classification and early diagnosis of PD by analyzing the electrocorticography (ECoG) and electromyogram (EMG) signals of both normal and PD rats., Methods: The study utilized ECoG power, EMG amplitude, and corticomuscular coherence values extracted from normal and PD rats to construct sleep-wake scoring models based on the support vector machine algorithm. Subsequently, we incorporated feature values that could act as diagnostic markers for PD and then retrained the models, which could encompass the identification of vigilance states and the diagnosis of PD., Results: Features extracted from occipital ECoG signals were more suitable for constructing sleep-wake scoring models than those from frontal ECoG (average Cohen's kappa: 0.73 vs. 0.71). Additionally, after retraining, the new models demonstrated increased sensitivity to PD and accurately determined the sleep-wake states of rats (average Cohen's kappa: 0.79)., Conclusion: This study accomplished the precise detection of substantia nigra lesions and the monitoring of sleep-wake states. The integration of circadian rhythm monitoring and disease state assessment has the potential to improve the efficacy of therapeutic strategies considerably., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Calcium (Ca2+)- and zinc Zn2+-dependent nucleases play pivotal roles in plant nuclear DNA degradation in programmed cell death (PCD). However, the mechanisms by which these two nucleases co-participate in PCD-associated nuclear DNA degradation remain unclear. Here, the spatiotemporal expression patterns of two nucleases (CrCAN and CrENDO1) were analyzed qualitatively and quantitatively during PCD in secretory cavity formation in Citrus reticulata 'Chachi' fruits. Results show that the middle and late initial cell stages and lumen-forming stages are key stages for nuclear degradation during the secretory cavity development. CAN and ENDO1 exhibited potent in vitro DNA degradation activity at pH 8.0 and pH 5.5, respectively. Quantitative real-time reverse-transcription polymerase chain reaction, in situ hybridization assays, the subcellular localization of Ca2+ and Zn2+, and immunocytochemical localization showed that CrCAN was activated at the middle and late initial cell stages, while CrENDO1 was activated at the late initial cell and lumen-forming stages. Furthermore, we used immunocytochemical double-labelling to simultaneously locate CrCAN and CrENDO1. The DNA degradation activity of the two nucleases was verified by simulating the change of intracellular pH in vitro. Our results also showed that CrCAN and CrENDO1 worked respectively and co-participated in nuclear DNA degradation during PCD of secretory cavity cells. In conclusion, we propose the model for the synergistic effect of Ca2+- and Zn2+-dependent nucleases (CrCAN and CrENDO1) in co-participating in nuclear DNA degradation during secretory cavity cell PCD in Citrus fruits. Our findings provide direct experimental evidence for exploring different ion-dependent nucleases involved in nuclear degradation during plant PCD., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates brain states by applying a weak electrical current to the brain cortex. Several studies have shown that anodal stimulation of the ipsilesional primary motor cortex (M1) may promote motor recovery of the affected upper limb in patients with stroke; however, a high-level clinical recommendation cannot be drawn in view of inconsistent findings. A priming brain stimulation protocol has been proposed to induce stable modulatory effects, in which an inhibitory stimulation is applied prior to excitatory stimulation to a brain area. Our recent work showed that priming theta burst magnetic stimulation demonstrated superior effects in improving upper limb motor function and neurophysiological outcomes. However, it remains unknown whether pairing a session of cathodal tDCS with a session of anodal tDCS will also capitalise on its therapeutic effects., Methods and Analysis: This will be a two-arm double-blind randomised controlled trial involving 134 patients 1-6 months after stroke onset. Eligible participants will be randomly allocated to receive 10 sessions of priming tDCS+robotic training, or 10 sessions of non-priming tDCS+robotic training for 2 weeks. The primary outcome is the Fugl-Meyer Assessment-upper extremity, and the secondary outcomes are the Wolf Motor Function Test and Modified Barthel Index. The motor-evoked potentials, regional oxyhaemoglobin level and resting-state functional connectivity between the bilateral M1 will be acquired and analysed to investigate the effects of priming tDCS on neuroplasticity., Ethics and Dissemination: The study has been approved by the Research Ethics Committee of the Shanghai Yangzhi Rehabilitation Center (reference number: Yangzhi2023-022) and will be conducted in accordance with the Declaration of Helsinki of 1964, as revised in 2013., Trial Registration Number: ChiCTR2300074681., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Main Conclusion: CgPG21 is mainly located in the cell wall, participates in the intercellular layer degradation of the cell wall during the formation of secretory cavity in the intercellular space-forming and lumen-expanding stages. The secretory cavity is a common structure in Citrus plants and is the main site for synthesis and accumulation of medicinal ingredients. The secretory cavity is formed in lysogenesis, when epithelial cells enter a process of programmed cell death. Pectinases are known to be involved in degradation of the cell wall during the cytolysis of secretory cavity cells, but the changes in cell structure, the dynamic characteristics of cell wall polysaccharides and the related genes regulating cell wall degradation are unclear. In this study, electron microscopy and cell wall polysaccharide-labeling techniques were used to study the main characteristics of cell wall degradation of the secreting cavity of Citrus grandis 'Tomentosa' fruits. At the same time, the full CDS length of the pectinase gene CgPG21 was cloned, encoding a protein composed of 480 amino acids. CgPG21 is mainly located in the cell wall, participates in the degradation of the intercellular layer of the cell wall during the development of the secretory cavity, and plays an important role in the formation of the secretory cavity in the intercellular space-forming and lumen-expanding stages. With the development of secretory cavity, the cell wall polysaccharides of epithelial cells gradually degrade. CgPG21 is mainly involved in the intercellular layer degradation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vacuolar processing enzymes (VPEs) with caspase-1-like activity are closely associated with vacuole rupture. The destruction of vacuoles is one of the characteristics of programmed cell death (PCD) in plants. However, whether VPE is involved in the vacuole destruction of cells during secretory cavity formation in Citrus plants remains unclear. This research identified a CgVPE1 gene that encoded the VPE and utilized cytology and molecular biology techniques to explore its temporal and spatial expression characteristics during the PCD process of secretory cavity cells in the Citrus grandis 'Tomentosa' fruit. The results showed that CgVPE1 is an enzyme with VPE and caspase-1-like activity that can self-cleave into a mature enzyme in an acidic environment. CgVPE1 is specifically expressed in the epithelial cells of secretory cavities. In addition, it mainly accumulates in vacuoles before it is ruptured in the secretory cavity cells. The spatial and temporal immunolocalization of CgVPE1 showed a strong relationship with the change in vacuole structure during PCD in secretory cavity cells. In addition, the change in the two types of VPE proteins from proenzymes to mature enzymes was closely related to the change in CgVPE1 localization. Our results indicate that CgVPE1 plays a vital role in PCD, causing vacuole rupture in cells during the development of the secretory cavity in C. grandis 'Tomentosa' fruits.

Objective: To evaluate the efficacy and safety of combined traditional Chinese medicine in the adjuvant treatment of proliferative diabetic retinopathy (PDR) by Meta-analysis., Methods: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang databases were searched by computer. Random controlled clinical trials (RCTS) using traditional Chinese medicine as adjuvant therapy for proliferative diabetic retinopathy were screened, and Stata16.0 software was used to perform meta-analysis on the final included literatures., Results: A total of 18 studies involving 1392 patients were included. Meta-analysis showed that the clinical effective rate OR=2.99 ( CI : 2.18-4.10, I 2  =  42.7%, P <0.05); Visual acuity MD=0.10( CI : 0.06-0.13, I 2  =  0%, P <0.05); Fundus efficacy OR=5.47 ( CI : 1.33-22.51, I 2  =  71.4%, P <0.05); Neovascularisation regression rate OR=8 ( CI : 3.83-16.71, I 2  =  30.1%, P <0.05); Macular foveal thickness MD=-44.24 ( CI : -84.55-3.93, I 2  =  95.6%, P <0.05); Absorption of vitreous hemorrhage OR=4.7 ( CI : 2.26-9.77, I 2  =  0%, P <0.05); Fasting blood glucose MD=-0.23, ( CI : -0.38-0.07, I 2  =  0%, P <0.05); 2h postprandial blood glucose MD=-0.19 ( CI : -0.52-0.14, I 2  =  0%, P =0.25). From the results, the combined Chinese medicine adjuvant therapy showed better efficacy than the control group. A total of 69 kinds of traditional Chinese medicine were involved in 18 studies, among which the top four applied frequencies were Panax notoginseng, Rehmannia rehmannii, Astragalus membranaceus and Poria cocos. Most of the medicines were sweet and bitter in taste, the qi tended to be slight cold and cold, and the meridian tropism belongs to the liver meridian., Conclusion: The combination of traditional Chinese medicine adjuvant therapy has a good curative effect on PDR patients. However, the relevant clinical trials are few and more high-quality clinical trials are still needed, what's more the attention should be paid to the exploration of its safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huai, Huai, Su, Song, Li, Cao, Xin and Liu.)