The role of the SIRT1/NF-κB/NLRP3 pathway in the pyroptosis of lens epithelial cells under shortwave blue light radiation.

Cataracts are the world's number one blinding eye disease. Cataracts can only be effectively treated surgically, although there is a chance of surgical complications. One of the pathogenic processes of cataracts is oxidative stress, which closely correlated with pyroptosis. SIRT1 is essential for the regulation of pyroptosis. Nevertheless, the role of SIRT1 in formation of cataracts is unclear. In this work, we developed an in vitro model of shortwave blue light (SWBL)-induced scotomization in human lens epithelial cells (HLECs) and an in vivo model of SWBL-induced cataracts in rats. The study aimed to understand how the SIRT1/NF-κB/NLRP3 pathway functions. Additionally, the evaluation included cell death and the release of lactate dehydrogenase (LDH), a cytotoxicity marker, from injured cells. First, we discovered that SWBL exposure resulted in lens clouding in Sprague- Dawley (SD) rats and that the degree of clouding was positively linked to the duration of irradiation. Second, we discovered that SIRT1 exhibited antioxidant properties and was connected to the NF-κB/NLRP3 pathway. SWBL irradiation inhibited SIRT1 expression, exacerbated oxidative stress, and promoted nuclear translocation of NF-κB and the activation of the NLRP3 inflammasome, which caused LEC pyroptosis and ultimately led to cataract formation. Transient transfection to increase the expression of SIRT1 decreased the protein expression levels of NF-κB, NLRP3, caspase-1, and GSDMD, inhibited HLEC pyroptosis, and reduced the release of LDH, providing a potential method for cataract prevention and treatment.

Different Thicknesses of Acellular Porcine Corneal Stroma on Prognosis of Fungal Corneal Ulcers Treated by Lamellar Keratoplasty: A Five-Year Retrospective Study.

PURPOSE: To compare the prognosis and efficacy of acellular porcine corneal stroma (APCS) with different thicknesses for the treatment of fungal corneal ulcers by lamellar keratoplasty (LKP). METHODS: A total of 52 patients who underwent LKP with APCS for the treatment of fungal corneal ulcers were included in this retrospective study. Patients were divided into 2 groups according to the different thicknesses of APCS (0.30 ± 0.05 mm, L2 group, n = 20; 0.40 ± 0.05 mm, L3 group, n = 32). Observation indicators included best corrected visual acuity, graft transparency, corneal neovascularization, ocular irritation symptoms, corneal epithelial healing time, graft survival, central corneal thickness at 1 year after surgery, and postoperative complications. RESULTS: Compared with the L3 group, the L2 group had better postoperative best corrected visual acuity and graft transparency (P < 0.001), less corneal neovascularization (P < 0.001), and lower incidence of complications (P < 0.05). There were significant differences in ocular irritation symptoms between the 2 groups (P < 0.05) at 3 and 6 months postoperatively, which might be related to the higher recurrence rate and graft rejection rate in the L3 group. The comparison of postoperative epithelial healing time also showed significant differences in 2 groups (P < 0.01). The 1-year survival rate was up to 63.5% in both groups, with no significant difference (P < 0.05). However, the risk of transplantation was less in the L2 group. Both APCS thicknesses could provide adequate central corneal thickness at 1 year after surgery (P > 0.05). CONCLUSIONS: APCS was safe and effective in the treatment of fungal corneal ulcers by LKP. Thinner grafts should be preferred for LKP for fungal corneal ulcers to reduce the risk of grafting.

Associations of air pollution exposures in preconception and pregnancy with birth outcomes and infant neurocognitive development: analysis of the Complex Lipids in Mothers and Babies (CLIMB) prospective cohort in Chongqing, China.

OBJECTIVES: To investigate the associations of traffic-related air pollution exposures in early pregnancy with birth outcomes and infant neurocognitive development. DESIGN: Cohort study. SETTING: Eligible women attended six visits in the maternity clinics of two centres, the First Affiliated Hospital of Chongqing Medical University and Chongqing Health Centre for Women and Children. PARTICIPANTS: Women who were between 20 and 40 years of age and were at 11-14 weeks gestation with a singleton pregnancy were eligible for participation. Women were excluded if they had a history of premature delivery before 32 weeks of gestation, maternal milk allergy or aversion or severe lactose intolerance. 1273 pregnant women enrolled in 2015-2016 and 1174 live births were included in this analysis. EXPOSURES: Air pollution concentrations at their home addresses, including particulate matter with diameter ≤2.5 µm (PM2.5) and nitrogen dioxide (NO2), during pre-conception and each trimester period were estimated using land-use regression models. OUTCOME MEASURES: Birth outcomes (ie, birth weight, birth length, preterm birth, low birth weight, large for gestational age and small for gestational age (SGA) status) and neurodevelopment outcomes measured by the Chinese version of Bayley Scales of Infant Development. RESULTS: An association between SGA and per-IQR increases in NO2 was found in the first trimester (OR: 1.57, 95% CI: 1.06 to 2.32) and during the whole pregnancy (OR: 1.33, 99% CI: 1.01 to 1.75). Both PM2.5 and NO2 exposure in the 90 days prior to conception were associated with lower Psychomotor Development Index scores (ß: -6.15, 95% CI: -8.84 to -3.46; ß: -2.83, 95% CI: -4.27 to -1.39, respectively). Increased NO2 exposure was associated with an increased risk of psychomotor development delay during different trimesters of pregnancy. CONCLUSIONS: Increased exposures to NO2 during pregnancy were associated with increased risks of SGA and psychomotor development delay, while increased exposures to both PM2.5 and NO2 pre-conception were associated with adverse psychomotor development outcomes at 12 months of age. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16007700.

The effect of cultured autologous oral mucosal epithelial cells on ocular surface reconstruction.

Introduction: Oral epithelial cells were recently shown to be able to differentiate into corneal epithelium, and the efficacy of cultured autologous oral mucosal epithelial cells (CAOMEC) has been suggested by the presence of epithelium replacement. Therefore, the aim of this study was to evaluate the treatment outcome in limbal stem cell deficiency (LSCD) by adding CAOMEC to regular amniotic membrane (AM) treatment. Material and methods: Eyes with LSCD were randomized to two groups to undergo either autologous oral mucosal epithelial cell sheet (CAOMECS) combined with AM transplantation (A group) or AM transplantation alone (B group). Clinical outcome measures were corneal epithelium healing, best corrected visual acuity, symblepharon, corneal transparency, corneal neovascularization and ocular surface inflammation. Results: The normal corneal epithelialization rate in group A (73.33%) was higher than that in group B (35.48%), and the average healing time was shorter (3.45 ±2.12 weeks vs. 4.64 ±1.63 weeks). The symblepharon in the above two groups was improved in the first 3 months after surgery, but after 6 months, part of the B group had recurrence. In improving corneal transparency, group A has obvious advantages. Corneal neovascularization (CNV) was improved to some extent in the first 3 months after surgery, but group A (1.47 ±0.64) was better than group B (1.94 ±0.85) after 6 months. Both groups can improve the inflammatory state to some extent. Conclusions: The transplantation of CAOMECS offers a viable and safe alternative in the reconstruction of a stable ocular surface. The effect is better than that of traditional AM transplantation, mainly in promoting corneal epithelialization, improving ocular surface structure, and reducing fiber and vascular infiltration.

Grooved Microneedle Patch Augments Adoptive T Cell Therapy Against Solid Tumors via Diverting Regulatory T Cells.

The efficacy of adoptive T cell therapy (ACT) for the treatment of solid tumors remains challenging. In addition to the poor infiltration of effector T (Teff) cells limited by the physical barrier surrounding the solid tumor, another major obstacle is the extensive infiltration of regulatory T (Treg) cells, a major immunosuppressive immune cell subset, in the tumor microenvironment. Here, this work develops a grooved microneedle patch for augmenting ACT, aiming to simultaneously overcome physical and immunosuppressive barriers. The microneedles are engineered through an ice-templated method to generate the grooved structure for sufficient T-cell loading. In addition, with the surface modification of chemokine CCL22, the MNs could not only directly deliver tumor-specific T cells into solid tumors through physical penetration, but also specifically divert Treg cells from the tumor microenvironment to the surface of the microneedles via a cytokine concentration gradient, leading to an increase in the ratio of Teff cells/Treg cells in a mouse melanoma model. Consequently, this local delivery strategy of both T cell receptor T cells and chimeric antigen receptor T cells via the CCL22-modified grooved microneedles as a local niche could significantly enhance the antitumor efficacy and reduce the on-target off-tumor toxicity of ACT.

Identification of KRAS mutation-associated gut microbiota in colorectal cancer and construction of predictive machine learning model.

Gut microbiota has demonstrated an increasingly important role in the onset and development of colorectal cancer (CRC). Nonetheless, the association between gut microbiota and KRAS mutation in CRC remains enigmatic. We conducted 16S rRNA sequencing on stool samples from 94 CRC patients and employed the linear discriminant analysis effect size algorithm to identify distinct gut microbiota between KRAS mutant and KRAS wild-type CRC patients. Transcriptome sequencing data from nine CRC patients were transformed into a matrix of immune infiltrating cells, which was then utilized to explore KRAS mutation-associated biological functions, including Gene Ontology items and Kyoto Encyclopedia of Genes and Genomes pathways. Subsequently, we analyzed the correlations among these KRAS mutation-associated gut microbiota, host immunity, and KRAS mutation-associated biological functions. At last, we developed a predictive random forest (RF) machine learning model to predict the KRAS mutation status in CRC patients, based on the gut microbiota associated with KRAS mutation. We identified a total of 26 differential gut microbiota between both groups. Intriguingly, a significant positive correlation was observed between Bifidobacterium spp. and mast cells, as well as between Bifidobacterium longum and chemokine receptor CX3CR1. Additionally, we also observed a notable negative correlation between Bifidobacterium and GOMF:proteasome binding. The RF model constructed using the KRAS mutation-associated gut microbiota demonstrated qualified efficacy in predicting the KRAS phenotype in CRC. Our study ascertained the presence of 26 KRAS mutation-associated gut microbiota in CRC and speculated that Bifidobacterium may exert an essential role in preventing CRC progression, which appeared to correlate with the upregulation of mast cells and CX3CR1 expression, as well as the downregulation of GOMF:proteasome binding. Furthermore, the RF model constructed on the basis of KRAS mutation-associated gut microbiota exhibited substantial potential in predicting KRAS mutation status in CRC patients.IMPORTANCEGut microbiota has emerged as an essential player in the onset and development of colorectal cancer (CRC). However, the relationship between gut microbiota and KRAS mutation in CRC remains elusive. Our study not only identified a total of 26 gut microbiota associated with KRAS mutation in CRC but also unveiled their significant correlations with tumor-infiltrating immune cells, immune-related genes, and biological pathways (Gene Ontology items and Kyoto Encyclopedia of Genes and Genomes pathways). We speculated that Bifidobacterium may play a crucial role in impeding CRC progression, potentially linked to the upregulation of mast cells and CX3CR1 expression, as well as the downregulation of GOMF:Proteasome binding. Furthermore, based on the KRAS mutation-associated gut microbiota, the RF model exhibited promising potential in the prediction of KRAS mutation status for CRC patients. Overall, the findings of our study offered fresh insights into microbiological research and clinical prediction of KRAS mutation status for CRC patients.

Comparison of keratoplasty outcomes at the scar versus edema stages of keratoconus.

PURPOSE: To assess the outcomes of deep anterior lamellar keratoplasty or penetrating keratoplasty at the scar and the edema stages. METHODS: Forty-five patients (45 eyes) with keratoconus scar stage (scar group, n=26; penetrating keratoplasty a subgroup, n=7; deep anterior lamellar keratoplasty b subgroup, n=19) and keratoconus edema stage (edema group, n=19; penetrating keratoplasty c subgroup, n=12; deep anterior lamellar keratoplasty d group, n=7) who received penetrating keratoplasty or deep anterior lamellar keratoplasty from 2000 to 2022 were retrospectively studied. At 1, 6, and 12 months after surgery, the best-corrected visual acuity, astigmatism, spherical equivalent, corneal endothelial cell density, and complications were analyzed. RESULTS: The best-corrected visual acuity and average corneal endothelial cell loss rate were not significantly different between the scar and edema groups (p>0.05). At 6 and 12 months after surgery, the astigmatism and spherical equivalent in the scar group were significantly lower than those in the edema group (p<0.05). The spherical equivalent of the deep anterior lamellar keratoplasty b subgroup was lower than that of the penetrating keratoplasty a subgroup in the scar group 6 months after surgery (p<0.05). In the edema group, there was no significant difference in spherical equivalent between subgroups (p>0.05). There were no significant differences in best-corrected visual acuity and astigmatism between subgroups within the two groups (p>0.05). In comparison to the scar group, the edema group experienced more complications. According to a survival analysis, there was no statistically significant difference between the scar group and the edema group regarding the progression of vision. CONCLUSIONS: In terms of the outcomes and prognosis for vision after keratoplasty with edema stage and scar stage, deep anterior lamellar keratoplasty may be as effective as penetrating keratoplasty.

Wet bio-amniotic membrane plugging combined with transplantation in the treatment of small corneal perforations.

PURPOSE: Wet bio-amniotic membrane plugging combined with transplantation is a novel option that combined amniotic membrane plugging with amniotic membrane transplantation for the treatment of small corneal perforations. This study aimed to evaluate the efficacy of wet bio-amniotic membrane plugging in the treatment of small corneal perforations and compared it with that of the penetrating keratoplasty procedure. METHODS: Forty patients (41 eyes) with small corneal perforations <3 mm in diameter treated at our hospital between July 2018 and January 2021 were retrospectively included. Among them, 21 eyes were treated with wet bio-amniotic membrane plugging (wet bio-amniotic membrane plugging group), and 20 eyes were treated with penetrating keratoplasty procedure (penetrating keratoplasty procedure group). The best-corrected visual acuity, anterior chamber formation, corneal thickness, primary disease control, postoperative complications, and graft survival rate were assessed. RESULTS: No significant difference in baseline characteristics was found between the wet bio-amniotic membrane plugging and penetrating keratoplasty procedure groups (p>0.05). The postoperative control rates of primary diseases in the wet bio-amniotic membrane plugging and penetrating keratoplasty procedure groups were 95.2% and 90.0%, respectively (p=0.481). Visual acuity was improved 6 months after the operation in the wet bio-amniotic membrane plugging group and was improved at postoperative 1 month in the penetrating keratoplasty procedure group. The formation time of the anterior chamber in the wet bio-amniotic membrane plugging group was significantly shorter than that in the penetrating keratoplasty procedure group (p=0.023). The corneal thickness of the two groups significantly increased 12 months after the operation; however, the degree of thickening in the penetrating keratoplasty procedure group was higher than that in the wet bio-amniotic membrane plugging group (p<0.001). During the follow-up, postoperative complications were not different between the two groups (p>0.999). CONCLUSION: The results suggest that wet bio-amniotic membrane plugging is effective and safe in the treatment of small corneal perforations. Thus, it can be used as an emergency treatment alternative to penetrating keratoplasty procedure for small corneal perforations.

Ultrasensitive SERS quantitative detection of antioxidants via diazo derivatization reaction and deep learning for signal fluctuation mitigation.

Synthetic antioxidants serve as essential protectors against oxidation and deterioration of edible oils, however, prudent evaluation is necessary regarding potential health risks associated with excessive intake. The direct adsorption of antioxidants onto conventional surface-enhanced Raman scattering (SERS) substrates is challenging due to the presence of phenolic hydroxyl groups in their molecular structures, resulting in weak Raman scattering signals and rendering direct SERS detection difficult. In this study, a diazo derivatization reaction was employed to enhance SERS signals by converting antioxidant molecules into azo derivatives, enabling the amplification of the weak Raman scattering signals through the strong vibrational modes induced by the N = N double bond. The resulting diazo derivatives were characterized using UV-visible absorption and infrared spectroscopy, confirming the occurrence of diazo derivatization of the antioxidants. The proposed method successfully achieved the rapid detection of three commonly used synthetic antioxidants, namely butylated hydroxyanisole (BHA), tert-butylhydroquinone (TBHQ), and propyl gallate (PG) on interfacial self-assembled gold nanoparticles. Furthermore, rapid predictions of BHA, PG, and TBHQ within the concentration range of 1 × 10-6 to 2 × 10-3 mol/L were achieved by integrating a convolutional neural network model. The predictive range of this model surpassed the traditional quantitative method of manually selecting characteristic peaks, with linear coefficients (R2) of 0.9992, 0.9997, and 0.9997, respectively. The recovery of antioxidants in real soybean oil samples ranged from 73.0 % to 126.4 %. Based on diazo derivatization, the proposed SERS method eliminates the need for complex substrates and enables the analysis and determination of synthetic antioxidants in edible oils within 20 min, providing a convenient analytical approach for quality control in the food industry.

Adavosertib-encapsulated metal-organic frameworks for p53-mutated gallbladder cancer treatment via synthetic lethality.

Adavosertib (ADA) is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer (GBC). However, drug resistance due to DNA damage response compensation pathways and high toxicity limits further applications. Herein, estrone-targeted ADA-encapsulated metal-organic frameworks (ADA@MOF-EPL) for GBC synthetic lethal treatment by inducing conditional factors are developed. The high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor microenvironment. Ultrasound irradiation induces ADA@MOF-EPL to generate reactive oxygen species (ROS), which leads to a further increase in DNA damage, resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic lethality. The conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic toxicity. Moreover, ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors, revealing its potential as a broad-spectrum antitumor drug.

High-performance sono-piezoelectric nanocomposites enhanced by interfacial coupling effects for implantable nanogenerators and actuators.

Transcutaneous energy-harvesting technology based on ultrasound-driven piezoelectric nanogenerators is the most promising technology in medical and industrial applications. Based on ultrasonic coupling effects at the interfaces, the interfacial architecture is a critical parameter to attain desirable electromechanical properties of nanocomposites. Herein, we successfully synthesized core-conductive shell-structured BaTiO3@Carbon [BT@Carbon] nanoparticles [NPs] as nanofillers to design implantable poly(vinylidenefluoride-co-chlorotrifluoroethylene)/BT@Carbon [P(VDF-CTFE)/BT@Carbon] piezoelectric nanogenerators (PENGs) and actuators for harvesting ultrasound (US) underneath the skin. For US-driven PENGs, the electrons and holes are generated not only from the interfaces between the BT@Carbon NPs and the matrix, but also from the dipoles vibrating in the smaller lamellae of ferroelectric ß-phase crystals in poled nanocomposites. Remarkably, P(VDF-CTFE)/BT@Carbon piezoelectric nanogenerators could attain an extraordinary output power of 521 µW cm-2 under ultrasound stimulation, which is far greater than that of force-induced PVDF-based nanogenerators and other ultrasound-driven triboelectric generators. Furthermore, the US-PENG actuator system, which is composed of an amplifier and a microcontroller, could efficiently convert ultrasonic energy into electricity or instructions to switch on/off small electronics in the tissues and organs of mice. Finally, the nanocomposite-based US-driven PENGs have a good biocompatibility, with no cytotoxicity or immune response in vivo, indicating their potential for developing wireless power generators and actuators for medical implant devices.

Evolutionary game analysis for multi-level collaborative governance under public crisis in China: From a value perception perspective.

In a risk society, the survival and development of humans are facing threats of complex and severe public crisis events. Public participation in collaborative governance (CG) of public crisis events is increasingly recognized as an important direction for the reform of the current and future emergency management system. Previous studies of CG have mainly focused on the macro level and ignored to address micro-level discussions of the behavioral strategy evolution of stakeholders. From a fresh value perception perspective, this study constructs an evolutionary game model to clarify the evolution mechanism of multi-level emergency CG. First, the value perception model is built based on Prospect Theory and Mental Accounting to optimize the traditional game matrix. Second, the evolutionary stability is analyzed to solve the system evolution law. Finally, numerical simulation is conducted in the case of Heilongjiang province, a main region of food and energy supply in China. Results showed that (1) the CG game system has a complex evolutionary path; (2) the behavior of game players is affected by perceived incomes and perceived costs; (3) compared with the reference value and the risk aversion coefficient of income accounts, game players are more sensitive to that of cost accounts; (4) enhancing the perceived value of public psychological satisfaction and government reputation is helpful for the long-term construction of CG. Overall, this study aims to highlight the potential utility of value perception in promoting effective implementations of CG and to provide new insights for the development of CG in China and other countries.

Comparison of keratoplasty outcomes at the scar versus edema stages of keratoconus

ABSTRACT Purpose: To assess the outcomes of deep anterior lamellar keratoplasty or penetrating keratoplasty at the scar and the edema stages. Methods: Forty-five patients (45 eyes) with keratoconus scar stage (scar group, n=26; penetrating keratoplasty a subgroup, n=7; deep anterior lamellar keratoplasty b subgroup, n=19) and keratoconus edema stage (edema group, n=19; penetrating keratoplasty c subgroup, n=12; deep anterior lamellar keratoplasty d group, n=7) who received penetrating keratoplasty or deep anterior lamellar keratoplasty from 2000 to 2022 were retrospectively studied. At 1, 6, and 12 months after surgery, the best-corrected visual acuity, astigmatism, spherical equivalent, corneal endothelial cell density, and complications were analyzed. Results: The best-corrected visual acuity and average corneal endothelial cell loss rate were not significantly different between the scar and edema groups (p>0.05). At 6 and 12 months after surgery, the astigmatism and spherical equivalent in the scar group were significantly lower than those in the edema group (p<0.05). The spherical equivalent of the deep anterior lamellar keratoplasty b subgroup was lower than that of the penetrating keratoplasty a subgroup in the scar group 6 months after surgery (p<0.05). In the edema group, there was no significant difference in spherical equivalent between subgroups (p>0.05). There were no significant differences in best-corrected visual acuity and astigmatism between subgroups within the two groups (p>0.05). In comparison to the scar group, the edema group experienced more complications. According to a survival analysis, there was no statistically significant difference between the scar group and the edema group regarding the progression of vision. Conclusions: In terms of the outcomes and prognosis for vision after keratoplasty with edema stage and scar stage, deep anterior lamellar keratoplasty may be as effective as penetrating keratoplasty.

Wet bio-amniotic membrane plugging combined with transplantation in the treatment of small corneal perforations

ABSTRACT Purpose: Wet bio-amniotic membrane plugging combined with transplantation is a novel option that combined amniotic membrane plugging with amniotic membrane transplantation for the treatment of small corneal perforations. This study aimed to evaluate the efficacy of wet bio-amniotic membrane plugging in the treatment of small corneal perforations and compared it with that of the penetrating keratoplasty procedure. Methods: Forty patients (41 eyes) with small corneal perforations <3 mm in diameter treated at our hospital between July 2018 and January 2021 were retrospectively included. Among them, 21 eyes were treated with wet bio-amniotic membrane plugging (wet bio-amniotic membrane plugging group), and 20 eyes were treated with penetrating keratoplasty procedure (penetrating keratoplasty procedure group). The best-corrected visual acuity, anterior chamber formation, corneal thickness, primary disease control, postoperative complications, and graft survival rate were assessed. Results: No significant difference in baseline characteristics was found between the wet bio-amniotic membrane plugging and penetrating keratoplasty procedure groups (p>0.05). The postoperative control rates of primary diseases in the wet bio-amniotic membrane plugging and penetrating keratoplasty procedure groups were 95.2% and 90.0%, respectively (p=0.481). Visual acuity was improved 6 months after the operation in the wet bio-amniotic membrane plugging group and was improved at postoperative 1 month in the penetrating keratoplasty procedure group. The formation time of the anterior chamber in the wet bio-amniotic membrane plugging group was significantly shorter than that in the penetrating keratoplasty procedure group (p=0.023). The corneal thickness of the two groups significantly increased 12 months after the operation; however, the degree of thickening in the penetrating keratoplasty procedure group was higher than that in the wet bio-amniotic membrane plugging group (p<0.001). During the follow-up, postoperative complications were not different between the two groups (p>0.999). Conclusion: The results suggest that wet bio-amniotic membrane plugging is effective and safe in the treatment of small corneal perforations. Thus, it can be used as an emergency treatment alternative to penetrating keratoplasty procedure for small corneal perforations.

Electron-beam writing of a relaxor ferroelectric polymer for multiplexing information storage and encryption.

To meet the strong demand for high-level encryption security, several efforts have been focused on developing new encryption techniques with high density and data security. Herein we employed a template-free electron beam lithography (EBL) technique to write various nanopatterns on poly(vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) (P(VDF-TrFE-CTFE)) films and applied it to electron-beam/electric multiplexing memory. Furthermore, electron beams can arbitrarily tailor down the domain structure evolutions and dipole directions, as proved by a combination of AFM-IR and PFM. Finally, our devices could function concurrently as an electron-beam write-only-memory (EB-WOM) and FeRAM, where the information could be encoded with the metastable phase evolutions from the ferroelectric phase to the paraelectric phase and variable bi-level ferroelectric signals. Our systematic study provides an inspiring idea for the design of information encryption devices with high-security requirements in flexible electronic fields.

The abundance and diversity of antibiotic resistance genes in layer chicken ceca is associated with farm enviroment.

Industrialized layer chicken feedlots harbor complex environmental microbial communities that affect the enrichment and exchange of gut bacteria and antibiotic resistance genes (ARGs). However, the contribution of different environmental sources to the gut ARGs of layer chickens is not clear. Here, layer chicken gut and environmental samples (air, water, feed, cage, feather, maternal hen feces, uropygial glands) were collected during the early 3 month period before the laying of eggs, and the source and characteristics of the gut microorganisms and ARGs were analyzed by performing 16S rRNA and metagenomic sequencing. The results showed that the abundances of Bacteroidetes and Actinobacteria in cecum of layer chickens gradually increased, while that of Proteobacteria decreased with age, and the number and relative abundance of ARGs decreased significantly with age. On day 5, 57% of the layer chicken cecal ARGs were from feather samples, and 30% were from cage samples. Subsequently, the contribution of cage ARGs became progressively more prominent over time. At days 30 and 57, the contribution of cage ARGs to the chick cecal ARGs reached 63.3 and 69.5%, respectively. The bacterial community composition (especially the abundances of Klebsiella pneumoniae and Escherichia coli) was the major factor impacting the ARG profile. K. pneumoniae and E. coli were mainly transmitted from feathers to the layer chicken cecum, and the contribution rates were 32 and 3.4%, respectively. In addition, we observed the transmission of ARG-carrying bacteria (Bacteroides fragilis) from the cage to the gut, with a contribution rate of 11.5%. It is noteworthy that B. fragilis is an opportunistic pathogen that may cause diarrhea in laying hens. These results can provide reference data for the healthy breeding of layer chickens and the prevention and control of ARG pollution.

2-Deoxyglucose drives plasticity via an adaptive ER stress-ATF4 pathway and elicits stroke recovery and Alzheimer's resilience.

Intermittent fasting (IF) is a diet with salutary effects on cognitive aging, Alzheimer's disease (AD), and stroke. IF restricts a number of nutrient components, including glucose. 2-deoxyglucose (2-DG), a glucose analog, can be used to mimic glucose restriction. 2-DG induced transcription of the pro-plasticity factor, Bdnf, in the brain without ketosis. Accordingly, 2-DG enhanced memory in an AD model (5xFAD) and functional recovery in an ischemic stroke model. 2-DG increased Bdnf transcription via reduced N-linked glycosylation, consequent ER stress, and activity of ATF4 at an enhancer of the Bdnf gene, as well as other regulatory regions of plasticity/regeneration (e.g., Creb5, Cdc42bpa, Ppp3cc, and Atf3) genes. These findings demonstrate an unrecognized role for N-linked glycosylation as an adaptive sensor to reduced glucose availability. They further demonstrate that ER stress induced by 2-DG can, in the absence of ketosis, lead to the transcription of genes involved in plasticity and cognitive resilience as well as proteostasis.

Design and characterization of molecular, crystal and interfacial structures of PVDF-based dielectric nanocomposites for electric energy storage.

PVDF-based polymers with polar covalent bonds are next-generation dielectric materials for electric energy storage applications. Several types of PVDF-based polymers, such as homopolymers, copolymers, terpolymers and tetrapolymers, were synthesized by radical addition reactions, controlled radical polymerizations, chemical modifications or reduction with the monomers of vinylidene fluoride (VDF), tetrafluoroethylene (TFE), trifluoroethylene (TrFE), hexafluoropropylene (HFP) and chlorotrifluoroethylene (CTFE). Owing to rich molecular structures and complicated crystal structures, PVDF-based dielectric polymers can show versatile dielectric polarization properties, including normal ferroelectrics, relaxor ferroelectrics, anti-ferroelectrics and linear dielectrics, which are beneficial for designing polymer films with high capacity and high charge-discharge efficiency for capacitor applications. Furthermore, to satisfy the requirements of practical high-capacity capacitors, the polymer nanocomposite method is another promising strategy to achieve high-capacitance dielectric materials by the addition of high-dielectric ceramic nanoparticles, moderate-dielectric nanoparticles (MgO, and Al2O3), high-insulation nanosheets (BN), etc. It is concluded with the current problems and future perspectives of interfacial engineering, such as core-shell strategies and hierarchical interfaces in polymer-based composite dielectrics for high-energy-density capacitor applications. In addition, an in-depth understanding of the roles of interfaces on the dielectric properties of nanocomposites can be achieved by indirect analysis techniques (theoretical simulation) and direct analysis techniques (scanning probe microscopy). Our systematic discussions on molecular, crystal and interfacial structures provide guidance for designing fluoropolymer-based nanocomposites for high-performance capacitor applications.

Spatial assessment of the attributable burden of disease due to transportation noise in England.

BACKGROUND: Noise pollution from transportation is one of the leading contributors to the environmental disease burden in Europe. We provide a novel assessment of spatial variations of these health impacts within a country, using England as an example. METHODS: We estimated the burden of annoyance (highly annoyed), sleep disturbance (highly sleep disturbed), ischemic heart disease (IHD), stroke, and diabetes attributable to long-term transportation noise exposures in England for the adult population in 2018 down to local authority level (average adult population: 136,000). To derive estimates, we combined literature-informed exposure-response relationships, with population data on noise exposures, disease, and mortalities. Long-term average noise exposures from road, rail and aircraft were sourced from strategic noise mapping, with a lower exposure threshold of 50 dB (decibels) Lden and Lnight. RESULTS: 40 %, 4.5 % and 4.8 % of adults in England were exposed to road, rail, and aircraft noise exceeding 50 dB Lden. We estimated close to a hundred thousand (∼97,000) disability adjusted life years (DALY) lost due to road-traffic, ∼13,000 from railway, and âˆ¼ 17,000 from aircraft noise. This excludes some noise-outcome pairs as there were too few studies available to provide robust exposure-response estimates. Annoyance and sleep disturbance accounted for the majority of the DALYs, followed by strokes, IHD, and diabetes. London, the South East, and North West regions had the greatest number of road-traffic DALYs lost, while 63 % of all aircraft noise DALYs were found in London. The strategic noise mapping did not include all roads, which may still have significant traffic flows. In sensitivity analyses using modelled noise from all roads in London, the DALYs were 1.1x to 2.2x higher. CONCLUSION: Transportation noise exposures contribute to a significant and unequal environmental disease burden in England. Omitting minor roads from the noise exposure modelling leads to underestimation of the disease burden.

Ultra-low threshold continuous-wave quantum dot mini-BIC lasers.

Highly compact lasers with ultra-low threshold and single-mode continuous wave (CW) operation have been a long sought-after component for photonic integrated circuits (PICs). Photonic bound states in the continuum (BICs), due to their excellent ability of trapping light and enhancing light-matter interaction, have been investigated in lasing configurations combining various BIC cavities and optical gain materials. However, the realization of BIC laser with a highly compact size and an ultra-low CW threshold has remained elusive. We demonstrate room temperature CW BIC lasers in the 1310 nm O-band wavelength range, by fabricating a miniaturized BIC cavity in an InAs/GaAs epitaxial quantum dot (QD) gain membrane. By enabling effective trapping of both light and carriers in all three dimensions, ultra-low threshold of 12 µW (0.052 kW cm-2) is achieved at room temperature. Single-mode lasing is also realized in cavities as small as only 5 × 5 unit cells (~2.5 × 2.5 µm2 cavity size) with a mode volume of 1.16(λ/n)3. The maximum operation temperature reaches 70 °C with a characteristic temperature of T0 ~93.9 K. With its advantages in terms of a small footprint, ultra-low power consumption, and adaptability for integration, the mini-BIC lasers offer a perspective light source for future PICs aimed at high-capacity optical communications, sensing and quantum information.