The notion that proteasome inhibitor bortezomib (BTZ) induced intracellular oxidative stress resulting in peripheral neuropathy has been generally accepted. The association of mitochondrial dysfunction, cell apoptosis, and endoplasmic reticulum (ER) stress with intracellular oxidative stress is ambiguous and still needs to be investigated. The activation of activating transcription factor 3 (ATF3) is a stress-hub gene which was upregulated in dorsal root ganglion (DRG) neurons after different kinds of peripheral nerve injuries.To investigate a mechanism underlying the action of BTZ-induced intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress via activation of ATF3.Primary cultured DRG neurons with BTZ induced neurotoxicity and DRG from BTZ induced painful peripheral neuropathic rats were used to approach these questions.BTZ administration caused the upregulation of ATF3 paralleled with intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress in DRG neurons both in vitro and in vivo. Blocking ATF3 signaling by small interfering RNA (siRNA) gene silencing technology resulted in decreased intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress in DRG neurons after BTZ treatment.This study exhibited important mechanistic insight into how BTZ induces neurotoxicity through the activation of ATF3 resulting in intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress and provided a novel potential therapeutic target by blocking ATF3 signaling.
To investigate the relationship between semaphorin 7a expression and cell proliferation and migration in pterygium fibroblasts.Twenty-six patients with surgically diagnosed pterygium were enrolled, including 15 cases of primary pterygium and 11 cases of recurrent pterygium. In addition, 12 cases of normal conjunctival tissue were collected. The expression of semaphorin 7a in normal conjunctival tissue, primary pterygium and recurrent pterygium was detected by real-time polymerase chain reaction. Recurrent pterygium fibroblasts were isolated and cultured, and the expression of semaphorin 7a was silenced by small interfering RNA (siRNA) interference technique. Furthermore, the effects of si-semaphorin 7a interference on the mRNA and protein levels of β1-integrin, vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor (VEGFR), and on fibroblast proliferation were analyzed. Transwell assay was used to detect the effect of semaphorin 7a interference on fibroblast migration.Semaphorin 7a was highly expressed in the primary pterygium and recurrent pterygium samples than that of the normal conjunctival tissue. Compared with the primary pterygium, the expression of semaphoring 7a in the recurrent pterygium samples was significantly increased (P<0.05). The mRNA and protein expression levels of β1-integrin, VEGFA and VEGFR were decreased after si-semaphorin 7a transfection, and as well as the cell proliferation and migration.Semaphorin 7a might play important roles in the pathogenesis of pterygium by affecting the expression of β1-integrin, VEGFA and VEGFR.
Background: China has been undergoing tremendous demographic transitions towards an aging society. Although suboptimal diets and malnutrition are the leading risk factors for disease burden, capturing nutrition challenges faced by the aging population is challenging due to the limited national representative information available. This study aimed to provide a comprehensive picture of the nutrition status of mid-aged and elderly Chinese and its relation to geographical and socioeconomic factors. Methods: A total of 75,758 non-institutionalized adults aged 45-80 years from the 2010-2013 Chinese National Nutrition and Health Survey were included in this study to evaluate their nutritional status and prevalence of malnutrition problems including anemia, underweight, overweight and obesity. Dietary data from 33,418 participants in this sample were obtained through 24 hour-recall over three consecutive days combined with weighted food inventory. Nutrient intakes were estimated based on dietary records and comparison with Chinese Dietary Reference Intakes 2013 (DRIs). Malnutrition problems were reported with stratification for demographic, geographic, and socioeconomic variables. Odd ratios of risks factors for malnutrition were estimated through multilevel multiple logistic regression analysis. Findings: Chinese population mean intakes of nutrient-dense food groups including fruits, dairy, soy and nuts, eggs, fish and seafood, as well as vegetables were lower than recommendations. Conversely, consumption of fat- and sodium- contributing groups such as meat and poultry, cooking oil, salt and condiments were higher than recommendations.The low adherence to dietary recommendations led to inadequate micronutrient intakes compared to DRIs, especially for eight micronutrients (calcium, folate, magnesium, selenium, vitamin A, vitamin B1, vitamin B2, and vitamin C), with more than 50% of participants have intakes lower than Estimated Average Requirements (EAR). Older age groups showed lower percentages of nutrient adequacy. The overall prevalences of anemia, underweight, overweight and obesity were 10.9%, 3.7%, 36% and 14%, respectively. The combined prevalence of overweight and obesity was 51.3% for the middle-aged group (45-59 years) and 45.2% for the elderly group (60-80 years). After adjusting for confounders at both individual and province levels, being older, female, a rural resident and having lower education were factors associated with higher risk for anemia and underweight, while younger age, female, urban residency and higher income were factors associated with greater risk for being overweight and obese. Interpretation: The results provide reference data for the development of policy and interventions to substantiate the China National Nutrition Plan 2017-2030. Within Chinese adults, older people have the highest prevalence of malnutrition. We suggest three priorities which require attention and solution: addressing anemia and underweight in high risk groups, curbing overweight and obesity, and supporting healthy eating and balanced diets. Funding Statement: The China National Nutrition and Healthy Survey (CNNHS), the Chinese Center for Disease Control and Prevention (CDC). This secondary data analysis received financial support from the Nestlé Research Center. Declaration of Interests: This secondary data analysis received financial support from Nestlé Research Center. Co-author Kai Yu, Jing Yin, and Fabrizio Arigoni are employed by Nestlé Research Center. These authors contributed to the development of the manuscript, with no roles in the survey design and data analysis. Ethics Approval Statement: The study protocol was approved by the ethical review committee of the Chinese CDC. Written informed consent was obtained from all participants.
The aim of the present study was to evaluate the relationship between tumor necrosis factor‑α (TNF‑α) and the development of gastric cancer, and to investigate whether it can be used as a biological marker for gastric cancer. In the current study, a new meta‑analysis was performed to assess the association between TNF‑α gene polymorphisms and gastric cancer susceptibility. Subgroup analyses based on ethnicity, control population source and non‑cardia cancers were also conducted. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random‑effects model. TNF‑α 308 polymorphisms indicated a significant relationship with gastric cancer risk among a normal population [GA/AA vs. GG; 1.17 (1.10‑1.23)]. In analysis stratified by ethnicity, TNF‑α 238 displayed an association with gastric cancer risk in eastern populations [GA/AA vs. GG: 1.24 (1.02‑1.50)], but not in western populations [GA/AA vs. GG: 0.96 (0.79‑1.18)]. The overall ORs (95% CIs) for TNF‑α 857, TNF‑α 1031 and TNF‑α 863 were 1.13 (1.04‑1.24), 0.94 (0.85‑1.05) and 0.89 (0.78‑1.02), respectively, under dominant genetic model comparison. Among the above three SNPs, only TNF‑α 857 was robustly associated with gastric cancer inclination, and this association remained consistently robust when limited to non‑cardia gastric cancers [GA/AA vs. GG: 1.16 (1.03‑1.31)]. TNF‑α 308 and TNF‑α 857 genotypes were potential risk factors of statistical significance in gastric cancer, and TNF‑α 238 indicated to be significantly associated with gastric cancer risk only in eastern populations. TNF‑α 1031 and TNF‑α 863 were not significantly associated with gastric cancer risk.
The notorious defects in the grain boundaries (GBs) and surfaces trigger serious nonradiative recombination and interfacial charge losses, concomitantly exacerbating the deterioration of photovoltaic performance and phase stability of CsPbI2Br perovskite solar cells. In this work, a comprehensive dual-passivation strategy enabled by formamidine salts (FADP) is developed to annihilate defects both inside the GBs and over the surface. It is shown that formamidinothiourea (FATU) additive could effectively modulate crystallization and afford to passivate both shallow-/deep-level defects at GBs, thereby endowing CsPbI2Br films with reduced lattice micro-strains and enlarged grains over 2 μm. Meanwhile, formamidinium bromine (FABr) post-treatment can efficiently heal the defective surface and realize cationic exchange with below CsPbI2Br films, forming a gradient band alignment at the CsPbI2Br/HTL interface. Profiting from ameliorated crystallization, inhibited GBs/surface charge recombination and facilitated hole transport ability, the novel FADP strategy substantially lifts the Voc from 1.22 V to 1.34 V, yielding a champion PCE of 16.74% with greatly reduced hysteresis. Coincidently, the unencapsulated FADP devices maintained 86.2% of initial PCE after aging at 25% RH for 40 days and 83.8% after 480 h aging under continuous illumination, which is pertinent to the inhibited defective region as well as Br-rich surface.
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