High molecular weight hyaluronic acid-liposome delivery system for efficient transdermal treatment of acute and chronic skin photodamage.

Photodamage is one of the most common causes of skin injury. High molecular weight hyaluronic acid (HHA) has shown immense potential in the treatment of skin photodamage by virtue of its anti-inflammatory, reparative, and antioxidative properties. However, due to its large molecular structure of HHA, HHA solution could only form a protective film on the skin surface in conventional application, failing to effectively penetrate the skin, which necessitates the development of new delivery strategies. Liposomes, with a structure similar to biological membranes, have garnered extensive attention as transdermal drug delivery carriers because of their advantages in permeability, dermal compatibility, and biosafety. Herein, we have developed a HHA-liposome transdermal system (HHL) by embedding HHA into the liposome structure using reverse evaporation, high-speed homogenization, and micro-jet techniques. The effective penetration and long-term residence of HHA in skin tissue were multidimensionally verified, and the kinetics of HHA in the skin were extensively studied. Moreover, it was demonstrated that HHL significantly strengthened the activity of human keratinocytes and effectively inhibits photo-induced cellular aging in vitro. Furthermore, a murine model of acute skin injury induced by laser ablation was established, where the transdermal system showed significant anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair, thereby demonstrating immense potential in accelerating skin wound healing. Meanwhile, HHL significantly ameliorated skin barrier dysfunction caused by simulated sunlight exposure, inhibited skin erythema, inflammatory responses, and oxidative stress, and promoted collagen expression in a chronic photodamage skin model. Therefore, this transdermal delivery system with biocompatibility represents a promising new strategy for the non-invasive application of HHA in skin photodamage, revealing the significant potential for clinical translation and broad application prospects. STATEMENT OF SIGNIFICANCE: The transdermal system utilizing hyaluronic acid-based liposomes enhances skin permeability and retains high molecular weight hyaluronic acid (HHL). In vitro experiments with human keratinocytes demonstrate significant skin repair effects of HHL and its effective inhibition of cellular aging. In an acute photodamage model, HHL exhibits stronger anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair. In a chronic photodamage model, HHL significantly improves skin barrier dysfunction, reduces oxidative stress induced by simulated sunlight, and enhances collagen expression.

Exploring the influence of transformer-based multimodal modeling on clinicians' diagnosis of skin diseases: A quantitative analysis.

Objectives: The study aimed to propose a multimodal model that incorporates both macroscopic and microscopic images and analyze its influence on clinicians' decision-making with different levels of experience. Methods: First, we constructed a multimodal dataset for five skin disorders. Next, we trained unimodal models on three different types of images and selected the best-performing models as the base learners. Then, we used a soft voting strategy to create the multimodal model. Finally, 12 clinicians were divided into three groups, with each group including one director dermatologist, one dermatologist-in-charge, one resident dermatologist, and one general practitioner. They were asked to diagnose the skin disorders in four unaided situations (macroscopic images only, dermatopathological images only, macroscopic and dermatopathological images, all images and metadata), and three aided situations (macroscopic images with model 1 aid, dermatopathological images with model 2&3 aid, all images with multimodal model 4 aid). The clinicians' diagnosis accuracy and time for each diagnosis were recorded. Results: Among the trained models, the vision transformer (ViT) achieved the best performance, with accuracies of 0.8636, 0.9545, 0.9673, and AUCs of 0.9823, 0.9952, 0.9989 on the training set, respectively. However, on the external validation set, they only achieved accuracies of 0.70, 0.90, and 0.94, respectively. The multimodal model performed well compared to the unimodal models, achieving an accuracy of 0.98 on the external validation set. The results of logit regression analysis indicate that all models are helpful to clinicians in making diagnostic decisions [Odds Ratios (OR) > 1], while metadata does not provide assistance to clinicians (OR < 1). Linear analysis results indicate that metadata significantly increases clinicians' diagnosis time (P < 0.05), while model assistance does not (P > 0.05). Conclusions: The results of this study suggest that the multimodal model effectively improves clinicians' diagnostic performance without significantly increasing the diagnostic time. However, further large-scale prospective studies are necessary.

A Highly Deficient Medium-Entropy Perovskite Ceramic for Electromagnetic Interference Shielding under Harsh Environment.

Materials that can provide reliable electromagnetic interference (EMI) shielding in highly oxidative atmosphere at elevated temperature are indispensable in the fast-developing aerospace field. However, most of conductor-type EMI shielding materials such as metals can hardly withstand the high-temperature oxidation, while the conventional dielectric-type materials cannot offer sufficient shielding efficiency in gigahertz (GHz) frequencies. Here, a highly deficient medium-entropy (ME) perovskite ceramic as an efficient EMI shielding material in harsh environment, is demonstrated. The synergistic effect of entropy stabilization and aliovalent substitution on A-site generate abnormally high concentration of Ti and O vacancies that are stable under high-temperature oxidation. Due to the clustering of vacancies, the highly deficient perovskite ceramic exhibits giant complex permittivity and polarization loss in GHz, leading to the specific EMI shielding effectiveness above 30 dB/mm in X-band even after 100 h of annealing at 1000 °C in air. Along with the low thermal conductivity, the aliovalent ME perovskite can serve as a bifunctional shielding material for applications in aircraft engines and reusable rockets.

Spatial Assessment of Land Suitability Potential for Agriculture in Nigeria.

From land cover analysis, cropland expansion was a major driving factor for land use land cover changes in Nigeria from 2000 to 2020. This further highlights the food production needs in the country. While this land use change indicates a significant alteration in land cover, it was exigent to assess land suitability using a Multi-Criteria Decision Analysis (MCDA) combined with geospatial techniques to identify areas with agricultural suitability potential and to analyze cropland suitability. The results showed that the country had 8% of very high suitability, high suitability (25%), moderate suitability (29%), and marginal suitability (25%) croplands. However, low suitability accounts for 14% of the entire cropland. The spatial distribution of cropland suitability shows that most areas in the South East, South South, and South West, respectively, have the most suitable cropland as they meet the biophysical conditions for crop production, followed by the North Central regions, while most places in the North (North East and North West) have a higher share of moderate to low suitability. This study highlights the potential of the country to target localized self-sufficiency. Therefore, this study recommends using the cropland suitability map to launch food security programs across the six geopolitical zones to maximize their inherent environmental potentials to alleviate the country's food production needs.

Lipoprotein-mimicking nanotherapeutics reconstituted with chenodeoxycholic acid modified protein for efficient tumor targeting.

Lipoprotein-derived nanotherapeutics based on endogenous lipid supramolecules have been regarded as an exceptional and promising approach for anti-tumor drug delivery. However, certain challenges associated with the main component apolipoprotein, such as limited availability, high cost, and insufficient specificity of relevant receptor expression, pose significant barriers to its widespread development and application. The objective of this study is to fabricate lipoprotein-mimicking nanocomposites, denoted as CA-P-rHDL by substituting apolipoprotein with chenodeoxycholic acid (CA) modified bovine serum albumin (BSA), and subsequently assess their tumor-targeting capability and anti-tumor efficacy. CA modified BSA (CA-BSA) was successfully synthesized and characterized by quantifying the degree of protein substitution. Subsequently, a nanostructured lipid carrier (NLC) mimicking the hydrophobic core of natural lipoproteins was attached with CA-BSA to form a lipoprotein-mimic nanocomplex termed as CA-rHDL. CA-rHDL was endowed with lipoprotein-like structures, favorable particle size, zeta potential and excellent paclitaxel encapsulation (termed as CA-P-rHDL). The internalization of CA-rHDL by HepG2 cells exhibited significantly superior efficiency, with a notably higher in HepG2 cells compared to LO2 cells. Confocal laser scanning microscopy revealed that CA-rHDL evaded lysosomal degradation and was evenly distributed throughout the cells. CCK-8 studies demonstrated that CA-P-rHDL exhibited significantly superior inhibition of tumor cells growth compared to other paclitaxel formulations in vitro. Moreover, in vivo imaging observation in H22 tumor-bearing mouse models exhibited a rapid and consistent accumulation of CA-rHDL within tumors, while CA-P-rHDL demonstrated remarkable efficacy against cancer in these mice. These exceptional capabilities of CA-P-rHDL can be attributed to the synergistic targeting effect facilitated by the combination of CA and BSA, rendering it a promising and versatile drug delivery system for targeted anticancer therapy. Consequently, CA-P-rHDL established a highly potential platform for simulating the reconstitution of supramolecular nanovehicles.

Cyanidin-3-O-glucoside and its derivative vitisin A alleviate androgenetic alopecia by exerting anti-androgen effect and inhibiting dermal papilla cell apoptosis.

Androgenetic alopecia (AGA), one of the most common forms of hair loss, lacks satisfactory treatment methods in modern society. This study employed an experimental design combining in vitro and in vivo approaches to explore the effects of Cyanidin-3-O-glucoside (C3G) and Carboxypyranocyanidin-3-O-glucoside (Vitisin A) on AGA. In human dermal papilla cells (HDPCs), both anthocyanins demonstrated inhibitory effects on androgen receptors, significantly reduced dihydrotestosterone (DHT) induced apoptosis of HDPCs, and regulated the secretion of Fibroblast growth factor 7 and Transforming growth factor beta 1. In vitro transdermal experiment revealed that both C3G and Vitisin A could penetrate mice skin, aided by the application of cream. Furthermore, in vivo experiments with mice indicated that application of C3G or Vitisin A cream effectively improved hair follicles miniaturization, regression, and apoptosis caused by DHT. The repression of Wnt10b and ß-catenin expression induced by DHT was prevented by C3G and Vitisin A in both cell and mouse model. Consequently, these findings suggest that C3G and Vitisin A could be considered as alternative methods for alleviating AGA.

A Low-Power SAR ADC with Capacitor-Splitting Energy-Efficient Switching Scheme for Wearable Biosensor Applications.

A low-power SAR ADC with capacitor-splitting energy-efficient switching scheme is proposed for wearable biosensor applications. Based on capacitor-splitting, additional reference voltage Vcm, and common-mode techniques, the proposed switching scheme achieves 93.76% less switching energy compared to the conventional scheme with common-mode voltage shift in one LSB. With the switching scheme, the proposed SAR ADC can lower the dependency on the accuracy of Vcm and the complexity of digital control logic and DAC driver circuits. Furthermore, the SAR ADC employs low-noise and low-power dynamic comparators utilizing multi-clock control, low sampling error sampling switches based on the bootstrap technique, and dynamic SAR logic. The simulation results demonstrate that the ADC achieves a 61.77 dB SNDR and a 78.06 dB SFDR and consumes 4.45 µW of power in a 180 nm process with a 1 V power supply, a full-swing input signal frequency of 93.33 kHz, and a sampling rate of 200 kS/s.

Intravenous Injection of Na Ions Aggravates Ang II-Induced Hypertension-Related Vascular Endothelial Injury by Increasing Transmembrane Osmotic Pressure.

Introduction: Extracellular protein nanoparticles (PNs) and ions perform synergistical functions in the control of transmembrane osmotic pressure (OP) under isotonic conditions. Intravenous injection may disrupt the ion balance and alter PN levels in blood plasma, changing transmembrane OP and damaging vascular endothelial cells. Methods: Na ions were injected into AngII-induced HUVECs to simulate cell injury in vitro, and tail vein infusion of Na ions into hypertensive rats was performed to assess vascular damage. Optical measurements using an intermediate filament (IF) tension probe were conducted to detect indicators related to transmembrane OP. Immunofluorescence, Western blotting and small interfering RNA (siRNA) transfection were employed to investigate inflammasomes and the relationship between Abl2 and inflammation. Results: Electrolyte injections with sodium ions (but not glucose and hydroxyethyl starch) induced the production of ASC and NLRP3 inflammasomes in Ang II-induced HUVECs; this in turn resulted in the disorder of calcium signals, and changes in transmembrane OP and cell permeability. Moreover, injection of Na ions into Ang II-induced HUVECs activated the mechanosensitive protein Abl2, involved in inflammation-induced transmembrane OP changes. A drug combination was identified that could induce OP recovery and block hyperpermeability induced by cytoplasmic inflammatory corpuscles in vivo and in vitro. Conclusion: Changes in extracellular PNs and ions following chemical stimuli (Ang II) participate in the regulation of transmembrane OP. Furthermore, injection of Na ions causes vascular endothelial injury in Ang II-induced cells in vitro and hypertension rats in vivo, suggesting it is not safe for hypertensive patients, and we propose a new drug combination as a solution.

Multimodal teaching analytics: the application of SCORM courseware technology integrating 360-degree panoramic VR in historical courses.

History courses are an essential part of a national education. The application of traditional courseware's media forms in education still requires further development and refinement. Herein, we report on a history courseware mode that integrates various historical teaching media, including 360-degree VR, paintings, maps, infographics, text, audio, and videos, based on the SCORM standard. These media elements are used to provide learners with a multimodal learning experience in history courses. We monitor the learning effects using EEG and questionnaires. The results show a significant improvement in our multimodal courseware technology compared to traditional courseware.

Versatile lipoprotein-inspired nanocomposites rescue Alzheimer's cognitive dysfunction by promoting Aß degradation and lessening oxidative stress.

The accumulation of amyloid-ß (Aß) into senile plaques and the resulting continuous oxidative stress are major pathogenic mechanisms in Alzheimer's disease (AD). In this study, we designed a lipoprotein-inspired nanoparticle to facilitate Aß clearance and alleviate oxidative stress for the treatment of AD. Lipoprotein-like nanocomposites (RLA-rHDL@ANG) were fabricated by assembling reconstituted high density lipoprotein (rHDL) with an apoE-derived peptide (RLA) with Aß binding and clearance capabilities, and were subsequently camouflaged using reactive oxygen species (ROS)-sensitive DSPE-TK-mPEG2000 and DSPE-TK-PEG3400-ANG with brain penetration as well as ROS scavenging ability. Immunoelectron microscopy, fluorescence colocalization, and enzyme linked immunosorbent assay, together with a thioflavin-T (ThT) fluorescence quantitative test, showed that RLA-rHDL@ANG possessed the ability of high binding affinity to both Aß monomers and oligomers, and disintegration of pre-formed Aß aggregates. ROS level monitoring and transmission electron microscopy (TEM) showed that RLA-rHDL@ANG possessed ROS sensitivity and consumption properties. Transcellular assay and in vivo imaging showed that RLA-rHDL@ANG effectively facilitated blood-brain barrier (BBB) penetration and intracerebral accumulation. It promoted the efficient degradation of Aß by microglia and neurons through lysosomal transport and elimination approaches. Four-week administration of RLA-rHDL@ANG effectively reduced Aß deposition, decreased the ROS level and improved cognitive functions in AD mice. These findings indicate that multifunctional RLA-rHDL@ANG may serve as a promising and feasible candidate for managing the progression of AD.

Proteomics analysis to investigate the potential mechanism of theacrine against UV-induced skin photodamage.

AIM: This study aimed to explore the underlying mechanism of theacrine treatment of UV-induced skin photodamage. MATERIALS AND METHODS: Tandem Mass Tag (TMT) relative quantitative proteomics analysis was used to characterize the proteins and pathways associated with the ability of theacrine to combat photodamage in mouse skin by modeling UV irradiation of the backs of ICR mice. RESULTS: Apoptosis-related proteins and signaling pathways play a key role in the ability of theacrine to protect against skin photodamage, according to proteomic and bioinformatics analysis; molecular docking and Western blotting further revealed that theacrine was associated with apoptosis-related proteins (p53, Bcl-2, Bax, caspase-3, and cleaved-caspase-3) with strong binding affinity, which can significantly reduce skin cell apoptosis induced by UV exposure. CONCLUSION: The findings revealed that theacrine can reduce UVB-induced epidermal damage by controlling the apoptosis signaling pathway, implying that theacrine could be a useful anti-UVB damage agent.

Crop Production and Security in Ningjin County of the North China Plain.

Stable growth in grain production is a critical challenge to ensure food security in North China Plain (NCP), an area dominated by smallholder farming. Food production and security of NCP largely depend on how smallholders farm their land. This study took Ningjin County of the NCP as an example to describe the characteristics of crop planting structure and the changes in crop production based on household surveys, statistics, various documents, and literature by descriptive statistics, calculation of crop self-sufficiency, and curve fitting, and aimed to reveal crop security and the influencing factors of crop production at the household level. The results were as follows: (1) Wheat and maize sown area accounted for 61.69% and 47.96% of the total sown area of crops during 2000-2020, increasing at a rate of 3.42% and 5.93%, respectively. Their planted areas increased from 27.52% and 15.54% in 2000 to 47.82% and 44.75% in 2020, respectively. (2) The self-sufficiency rate of maize showed a significant upward trend and reached its peak in 2019. the self-sufficiency rate of wheat also showed an increasing trend, from 192.87% to 617.37%, which indicates that wheat and maize can meet food self-sufficiency and the per capita grain yield is in a safe state. (3) The trends on wheat yield and fertilizer initially grew, then decreased, closely resembling an inverted "U", while the maize yield showed a pattern of increasing first and then basically remaining stable, similar to an "S" shape. A turning point for fertilizer use (550 kg/ha) was identified, indicating the limits of fertilizer use to increase yield. The national agricultural production and environmental protection policies, continuous improvement of crop varieties, as well as the farmers' traditional practices have significant impacts on crop production. This study will enhance management practices for improved yield, which can support the integrated management of agricultural production in intensive agricultural areas.

Improved Catalytic Performances of the NaOH-Treated ZSM-22 Zeolite in the 1-Butene Skeletal Isomerization Reaction: Effect of External Acid Sites.

In this paper, a series of alkaline-treated ZSM-22 zeolite samples were prepared by treating the parent ZSM-22 zeolite using NaOH aqueous solution with different concentrations. By investigating the effects of alkaline treatment on the parent ZSM-22 zeolite, we discovered that the alkaline treatment contributed to the reduction of Brønsted acid sites due to the coverage of extra-framework Al on its external surface. In addition, it was found that the alkaline-treated samples were favorable to the improvement of the isobutene yield and selectivity, while these features appeared to be low for the subsequent acid-washed counterparts in the skeletal isomerization reaction of 1-butene. These results indicate that the catalytic performance of ZSM-22 zeolite is related to reduced amounts of Brønsted acid sites in it. To further reveal the reasons for the promoted catalytic performances of the alkaline-treated ZSM-22 series zeolites, we studied the properties of coke deposited on the two series of samples using Raman spectroscopy and thermogravimetric analysis and mass spectrometry (TG/MS-TPO). It was shown that the carbon deposited on the alkaline-treated series samples was mainly distributed at the outer surface, while the coke was distributed to a relatively lesser extent at the exterior surface for the acid-washed series samples. Moreover, by partially passivating outer acid sites of the parent zeolite, the selected alkaline-treated zeolite, and acid-washed zeolite, their isobutene selectivities were all improved with the decrease in outer acid sites. These phenomena confirmed that the improved catalytic performances of the alkaline-treated samples are related to their decreased external Brønsted acid site density, which further demonstrated that the high isobutene yield and selectivity in the skeletal isomerization reaction of 1-butene is realized via the monomolecular reaction pathway of 1-butene.

Deep-learning-based survival prediction of patients with cutaneous malignant melanoma.

Background: This study obtained data on patients with cutaneous malignant melanoma (CMM) from the Surveillance, Epidemiology, and End Results (SEER) database, and used a deep learning and neural network (DeepSurv) model to predict the survival rate of patients with CMM and evaluate its effectiveness. Methods: We collected information on patients with CMM between 2004 and 2015 from the SEER database. We then randomly divided the patients into training and testing cohorts at a 7:3 ratio. The likelihood that patients with CMM will survive was forecasted using the DeepSurv model, and its results were compared with those of the Cox proportional-hazards (CoxPH) model. The calibration curves, time-dependent area under the receiver operating characteristic curve (AUC), and concordance index (C-index) were used to assess the prediction abilities of the model. Results: This study comprised 37,758 patients with CMM: 26,430 in the training cohort and 11,329 in the testing cohort. The CoxPH model demonstrated that the survival of patients with CMM was significantly influenced by age, sex, marital status, summary stage, surgery, radiotherapy, chemotherapy, postoperative lymph node dissection, tumor size, and tumor extension. The C-index of the CoxPH model was 0.875. We also constructed the DeepSurv model using the data from the training cohort, and its C-index was 0.910. We examined how well the aforementioned two models predicted outcomes. The 1-, 3-, and 5-year AUCs were 0.928, 0.837, and 0.855, respectively, for the CoxPH model, and 0.971, 0.947, and 0.942 for the DeepSurv model. The DeepSurv model presented a greater predictive effect on patients with CMM, and its reliability was better than that of the CoxPH model according to both the AUC value and the calibration curve. Conclusion: The DeepSurv model, which we developed based on the data of patients with CMM in the SEER database, was found to be more effective than the CoxPH model in predicting the survival time of patients with CMM.

Genetic causal relationship between age at menarche and benign oesophageal neoplasia identified by a Mendelian randomization study.

Objective: The occurrence and development of oesophageal neoplasia (ON) is closely related to hormone changes. The aim of this study was to investigate the causal relationships between age at menarche (AAMA) or age at menopause (AAMO) and benign oesophageal neoplasia (BON) or malignant oesophageal neoplasia (MON) from a genetic perspective. Methods: Genome-wide association study (GWAS) summary data of exposures (AAMA and AAMO) and outcomes (BON and MON) were obtained from the IEU OpenGWAS database. We performed a two-sample Mendelian randomization (MR) study between them. The inverse variance weighted (IVW) was used as the main analysis method, while the MR Egger, weighted median, simple mode, and weighted mode were supplementary methods. The maximum likelihood, penalized weighted median, and IVW (fixed effects) were validation methods. We used Cochran's Q statistic and Rucker's Q statistic to detect heterogeneity. The intercept test of the MR Egger and global test of MR pleiotropy residual sum and outlier (MR-PRESSO) were used to detect horizontal pleiotropy, and the distortion test of the MR-PRESSO analysis was used to detect outliers. The leave-one-out analysis was used to detect whether the MR analysis was affected by single nucleotide polymorphisms (SNPs). In addition, the MR robust adjusted profile score (MR-RAPS) method was used to assess the robustness of MR analysis. Results: The random-effects IVW results showed that AAMA had a negative genetic causal relationship with BON (odds ratio [OR] = 0.285 [95% confidence interval [CI]: 0.130-0.623], P = 0.002). The weighted median, maximum likelihood, penalized weighted median, and IVW (fixed effects) were consistent with random-effects IVW (P < 0.05). The MR Egger, simple mode and weighted mode results showed that AAMA had no genetic causal relationship with BON (P > 0.05). However, there were no causal genetic relationships between AAMA and MON (OR = 1.132 [95%CI: 0.621-2.063], P = 0.685), AAMO and BON (OR = 0.989 [95%CI: 0.755-1.296], P = 0.935), or AAMO and MON (OR = 1.129 [95%CI: 0.938-1.359], P = 0.200). The MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and IVW (fixed effects) were consistent with a random-effects IVW (P > 0.05). MR analysis results showed no heterogeneity, the horizontal pleiotropy and outliers (P > 0.05). They were not driven by a single SNP, and were normally distributed (P > 0.05). Conclusion: Only AAMA has a negative genetic causal relationship with BON, and no genetic causal relationships exist between AAMA and MON, AAMO and BON, or AAMO and MON. However, it cannot be ruled out that they are related at other levels besides genetics.

Anti-HER2 scFv-nCytc-Modified Lipid-Encapsulated Oxygen Nanobubbles Prepared with Bulk Nanobubble Water for Inducing Apoptosis and Improving Photodynamic Therapy.

Bulk nanobubbles fascinate scientists because of their stability over long periods of time and their ability to carry gases, leading to numerous potential applications. Considering the hypoxic tumor microenvironment and the advantages of bulk nanobubbles, lipid-encapsulated oxygen nanobubbles are prepared from free bulk oxygen nanobubbles in this study. The obtained carrier is then modified with a protein fused with the single-chain antibody of human epidermal growth factor receptor 2 (anti-HER2 scFv) and tandem-repeat cytochrome c (anti-HER2 scFv-nCytc) to enhance tumor targeting and induce tumor apoptosis. Copper phthalocyanine is used as the photosensitizer to demonstrate how the oxygen in the nanobubbles affects the efficiency of photodynamic therapy (PDT). The combination of anti-HER2 scFv-nCytc and PDT synergistically improves the therapeutic effect and alleviates hypoxia in tumors in vivo while causing little inflammatory response. Based on the findings, bulk nanobubble water shows promise in the targeted delivery of oxygen and can be combined with antibody therapy to enhance the efficiency of PDT.

Food Production and Consumption in Ordos of Inner Mongolia.

Ordos is an ecological fragile area in the upstream and midstream of the Yellow River and a component of the ecological security barrier on the northern frontier of China. With population growth in recent years, the contradiction between human beings and land resources has become increasingly prominent, leading to increased food security risks. Since 2000, the local government has implemented a series of ecological projects to guide farmers and herdsmen to transform from extensive production to intensive production, which has optimized the pattern of food production and consumption. It is necessary to study the balance between food supply and demand to evaluate food self-sufficiency. Here, we used the panel data from 2000 to 2020 collected based on random sampling surveys to reveal the characteristics of food production and consumption, the changes in food self-sufficiency rate and the dependence of food consumption on local production in Ordos. The results showed that food production and consumption dominated by grains have been increasing. The residents' diets were characterized by excessive consumption of grains and meat, and insufficient consumption of vegetables, fruits, and dairy foods. On the whole, the locality has achieved self-sufficiency, because the food supply exceeded the demand during the two decades. However, the self-sufficiency of different food types varied greatly, as some foods, such as wheat, rice, pork, poultry, and eggs, have not been self-sufficient. Due to the increased and diversified food demand of residents, food consumption became less dependent on local production and more dependent on food imported from the central and eastern China, which threatened local food security. The study can provide a scientific basis for decision-makers for the structural adjustment of agricultural and animal husbandry and the structural adjustment of food consumption, to ensure food security and sustainable utilization of land resources.

Myanmar's Land Cover Change and Its Driving Factors during 2000-2020.

Land use/cover change (LUCC) research occupies an important place in the study of global change. It is important for the ecological protection and long-term development of a place. Current research is lacking in the study of dynamic changes at the national level in Myanmar over long time periods and sequences. Quantitative research on the driving factors of LUCC is also lacking. This paper uses the GLC_FCS30 (Global Land-Cover product with Fine Classification System) dataset and socio-economic statistical data in Myanmar to conduct the study. The dynamic change process of LUC (land use/cover) was investigated using the land use dynamic degree, land use transfer matrix, and Sankey diagram. Principal component analysis was used to derive the main drivers of LUCC. The drivers were quantified using multiple linear stepwise regression analysis and specific factors were analyzed. The spatial scope of the study is Myanmar, and the temporal scope is 2000-2020. Results: (1) In 2020, the spatial distribution of LUC in Myanmar shows predominantly forests and croplands. Forests account for 56.64% of the country's total area. Agricultural land accounts for 25.59% of the country's total area. (2) Over the time scale of the study, the trend of LUCC in Myanmar showed significant shrinkage of evergreen broad-leaved forest and deciduous broad-leaved forest (a total shrinkage of -3.34 × 104 km2) and expansion of the other land types. (3) Over the time scale of the study, the dynamic changes in LUCC in Myanmar most occurred as an interconversion between two land types, such as between cropland and deciduous broad-leaved forest, evergreen broad-leaved forest and shrubland, deciduous broad-leaved forest and shrubland, evergreen broad-leaved forest and evergreen needle-leaved forest, and evergreen broad-leaved forest and deciduous broad-leaved forest. (4) The dynamics of LUC in Myanmar is mainly influenced by the socio-economic level of the country. Among them, the impact of agricultural level is the most obvious. Specifically, Myanmar's LUCC is mainly driven by urban population, urbanization rate, industrial value added, food production, and total population. Our research will enable the Myanmar government to make more scientific and rational land management and planning and to make more informed decisions. After understanding the basic situation of LUCC in Myanmar, the hydrological effects, biodiversity changes, and ecological service function changes due to land change in the region can be explored. This is the direction of future research.

Stiff matrix induced srGAP2 tension gradients control migration direction in triple-negative breast cancer.

Rationale: Cells migrating through interstitial matrix enables stiffening of the tumor micro-environment. To overcome the stiff resistance of extracellular matrix, aggressive cells require the extracellular mechanosensory activation and intracellular tension response. Mechanotransduction linker srGAP2 can synergistically control the mechanical-biochemical process of malignant cell migration. Methods: To mimic the tumor micro-environment containing abundant collagen fibers and moving durotaxis of triple-negative breast cancer cells, the stiff-directed matrix was established. The newly designed srGAP2 tension probe was used to real-time supervise srGAP2 tension in living cells. The phosphorylation sites responsible for srGAP2 tension were identified by phosphorylated mutagenesis. Transwell assays and Xenograft mouse model were performed to evaluate TNBC cells invasiveness in vitro and in vivo. Fluorescence staining and membrane protein isolation were used to detect protein localization. Results: The present study shows srGAP2 serves as a linker to transmit the mechanical signals among cytoskeleton and membrane. SrGAP2 exhibits tension gradients among different parts in the stiff-directionally migrating triple-negative breast cancer cells. Cells showing the polarized tension that increased in the leading edge move faster, particularly guided by the stiff interstitial matrix. The srGAP2 tension-directed cell migration results from the upstream events of PKCα-mediated phosphorylation at Ser206 in the F-bar domain of srGAP2. In addition, Syndecan-4 (SDC4), a transmembrane mechanoreceptor protein, drives PKCα regional recruit on the area of membrane trending deformation, which requires the distinct extent of extracellular mechanics. Conclusion: SDC4-PKCα polarized distribution leads to the intracellular tension gradient of srGAP2, presenting the extra- and intracellular physiochemical integration and essential for persistent cell migration in stiff matrix and caner progression. Targeting the srGAP2-related physicochemical signaling could be developed into the therapeutic strategies of inhibiting breast cancer cell invasion and durotaxis.

Dynamic nitric oxide/drug codelivery system based on polyrotaxane architecture for effective treatment of Candida albicans infection.

The low permeability of antifungal agents to fungal biofilms, which allows the continued survival of the fungus inside, is a key issue that makes fungal infections difficult to cure. Inspired by the unique dynamic molecule motion properties of the polyrotaxane (PR) nanomedicine, herein, a dynamic delivery system Clo@mPRP/NONOate was fabricated by co-loading nitric oxide (NO) and the antifungal drug clotrimazole (Clo) onto the α-cyclodextrin (α-CD) PR modified mesoporous polydopamine (mPDA) nanoparticles, in which pentaethylenehexamine (PEHA) was grafted to α-CDs. The cationic α-CDs endowed this dynamic NO/Clo codelivery system with the ability to effectively attach to fungal biofilms through electrostatic interaction, while the introduction of PRs with flexible molecule motion (slide and rotation of CDs) enhanced the permeability of nanoparticles to biofilms. Meanwhile, NO could effectively inhibit the formation of fungal hyphae, showing an dissipating effect on mature biofilms, and could be further combined with Clo to completely eradicate fungi inside the biofilms. In addition, the dynamic system Clo@mPRP/NONOate could efficiently and synergistically eliminate planktonic Candida albicans (C. albicans) in a safe and no toxic side effect manner, and effectively cured C. albicans-induced vaginal infection in mice. Therefore, this dynamic NO/Clo codelivery system provided an effective solution to the clinical treatment of C. albicans-induced vaginal infection, and the application prospect could even be extended to other microbial infectious diseases. STATEMENT OF SIGNIFICANCE: A dynamic codelivery system based on cationized cyclodextrin polyrotaxane combining nitric oxide and antifungal drugs clotrimazole was prepared to deal with the issue of clinical fungal biofilm infection. This dynamic codelivery system could be attached to the Candida albicans biofilms and penetrate into biofilm via flexible molecular mobility to effectively eradicate the fungi. This dynamic codelivery system could synergistically and efficiently eliminate planktonic-state Candida albicans, but did not show significant cytotoxicity to normal somatic cells.