Potential impacts of climate change on cephalopods in a highly productive region (Northwest Pacific): Habitat suitability and management.

Cephalopods occupy a mid-trophic level in marine ecosystems and are vital both ecologically and as fishery resources. However, under the pressure of climate change and fishing, the sustainability of cephalopod resources requires reasonable management. This study aims to study climate change and fishing impacts on the common economic cephalopod species habitats using species distribution models. We take the northwest Pacific Ocean region as an example, which stands out as a significant region for cephalopod production around the world. Results found that the habitats of cephalopods are moving to higher latitudes or deeper waters (Bohai Sea, mid-bottom Yellow Sea, and the Okinawa Trough waters) under climate change. Additionally, these regions are currently under lower fishing pressure, which suggests that species migration might mitigate the effects of warming and fishing. This study provides the large-scale assessment of the distribution range of cephalopods affected by climate change coping with fishing pressure in the northwest Pacific Ocean. By identifying climate refuges and key fishing grounds, we underscore the importance of this information for managing cephalopod resources in the context of climate adaptation and sustainable fishing practices.

Development and validation of an imprinted polymer based DGT for monitoring ß-blocker drugs in wastewater surveillance.

Wastewater surveillance is an effective and objective approach to monitor contaminant releases and drug usage in the catchment, the estimation requires accurate measurement. In this study, a novel diffusive gradients in thin-film (DGT) technique based on molecularly imprinted polymers (MIPs) for selective measurement of a class of widely prescribed cardiovascular drugs (ß-blockers) in wastewater was developed. The synthesized MIPs showed strong affinity and selectivity for the target compounds. The MIP-DGT had large effective capacities, its performance was independent of a wide range of environmental conditions, including pH (4.58 - 8.89), ionic strength (0.01 - 0.5 M) and dissolved organic matter (< 20 mg L-1). Biofouling had little effect on the uptake of target compounds within 7 days. MIP-DGT devices were applied in a Chinese urban WWTP alongside an auto-sampler. Metoprolol concentrations detected were much higher than other ß-blockers. Concentrations obtained using MIP-DGT were comparable to the 24 h composite samples using an autosampler. The estimated daily consumption calculated based on the data obtained with MIP-DGT implied that metoprolol and propranolol were the most popular ß-blockers in the studied area. Overall, the results in this study demonstrate that the MIP-DGT is a cost-effective, reliable and efficient tool for in situ wastewater monitoring.

Inhibition of OLR1 reduces SASP of nucleus pulposus cells by targeting autophagy-GATA4 axis.

Targeting cellular senescence and Senescence Associated Secretory Phenotype (SASP) through autophagy has emerged as a promising intervertebral disc (IVD) degeneration (IDD) treatment strategy in recent years. This study aimed to clarify the role and mechanism of autophagy in preventing IVD SASP. Methods involved in vitro experiments with nucleus pulposus (NP) tissues from normal and IDD patients, as well as an in vivo IDD animal model. GATA4's regulatory role in SASP was validated both in vitro and in vivo, while autophagy modulators were employed to assess their impact on GATA4 and SASP. Transcriptomic sequencing identified Oxidized low-density lipoprotein receptor 1 (OLR1) as a key regulator of autophagy and GATA4. A series of experiments manipulated OLR1 expression to investigate associated effects. Results demonstrated significantly increased senescent NP cells (NPCs) and compromised autophagy in IDD patients and animal models, with SASP closely linked to IDD progression. The aged disc milieu impeded autophagic GATA4 degradation, leading to elevated SASP expression in senescent NPCs. Restoring autophagy reversed senescence by degrading GATA4, hence disrupting the SASP cascade. Moreover, OLR1 was identified for its regulation of autophagy and GATA4 in senescent NPCs. Silencing OLR1 enhanced autophagic activity, suppressing GATA4-induced senescence and SASP expression in senescent NPCs. In conclusion, OLR1 was found to control autophagy-GATA4 and SASP, with targeted OLR1 inhibition holding promise in alleviating GATA4-induced senescence and SASP expression while delaying extracellular matrix degradation, offering a novel therapeutic approach for IDD management.

Cellulose nanocrystals-based optical organohydrogel fiber with customizable iridescent colors for strain and humidity response.

Stimuli-responsive optical hydrogels are widely used in various fields including environmental sensing, optical encryption, and intelligent display manufacturing. However, these hydrogels are susceptible to water losses when exposed to air, leading to structural damage, significantly shortened service lives, and compromised durability. This study presents mechanically robust, environmentally stable, and multi-stimuli responsive optical organohydrogel fibers with customizable iridescent colors. These fibers are fabricated by incorporating tunicate cellulose nanocrystals, alginate, and acrylamide in a glycerol-water binary system. The synthesized fibers exhibit high strength (1.38 MPa), moisture retention capabilities, and elastic properties. Furthermore, a sensor based on these fibers demonstrates high- and low-temperature resistance along with stimuli-responsive characteristics, effectively detecting changes in environmental humidity and strains. Moreover, the fiber sensor demonstrates continuous, repeatable, and quantitatively predictable moisture discoloration responses across a humidity range of 11 % and 98 %. During strain sensing, the optical-organohydrogel-based sensor demonstrates a large working strain (50 %) and excellent cycling stability, underscoring its potential for effectively monitoring a wide range of intricate human motions. Overall, the synthesized fibers and their simple fabrication method can elicit new avenues for numerous related applications including the large-scale implementation of advanced wearable technology.

Atypical KCNQ1/Kv7 channel function in a neonatal diabetes patient: Hypersecretion preceded the failure of pancreatic ß-cells.

KCNQ1/Kv7, a low-voltage-gated K+ channel, regulates cardiac rhythm and glucose homeostasis. While KCNQ1 mutations are associated with long-QT syndrome and type2 diabetes, its function in human pancreatic cells remains controversial. We identified a homozygous KCNQ1 mutation (R397W) in an individual with permanent neonatal diabetes melitus (PNDM) without cardiovascular symptoms. To decipher the potential mechanism(s), we introduced the mutation into human embryonic stem cells and generated islet-like organoids (SC-islets) using CRISPR-mediated homology-repair. The mutation did not affect pancreatic differentiation, but affected channel function by increasing spike frequency and Ca2+ flux, leading to insulin hypersecretion. With prolonged culturing, the mutant islets decreased their secretion and gradually deteriorated, modeling a diabetic state, which accelerated by high glucose levels. The molecular basis was the downregulated expression of voltage-activated Ca2+ channels and oxidative phosphorylation. Our study provides a better understanding of the role of KCNQ1 in regulating insulin secretion and ß-cell survival in hereditary diabetes pathology.

In vitro and in vivo degradation profile, biocompatibility of poly-L-lactic acid porous microspheres.

The objective of this study is to evaluate the in vitro and in vivo degradation profile and biocompatibility of poly-L-lactic acid (PLLA) porous microspheres (PMs) for their potential application as injectable microcarrier or micro-scaffolds materials in the research and clinical use of craniofacial cartilage repair. In this study, PLLA PMs prepared exhibited spherical shape and uniform surface pores followed by 24-week evaluations for degradation behavior and biocompatibility. In vitro degradation analysis encompassed morphological examination, pH monitoring, molecular weight analysis, thermodynamic assessment, and chemical structure analysis. After 12 weeks of in vitro degradation, PMs maintained a regular porous spherical structure. Molecular weight and glass transition temperature of PLLA PMs decreased over time, accompanying with an initial increase and subsequent decrease in crystallinity. Enzymatic degradation caused morphological changes and accelerated degradation in the in vitro studies. Finally, in vivo evaluations involved subcutaneous implantation of PLLA PMs in rats, demonstrating biocompatibility by enhancing type I and type III collagen regeneration as observed in histological analysis. The results demonstrated that PLLA PMs were able to maintain their spherical structure for 12 weeks, promoting the generation of collagen at the implantation site, meeting the time requirements for craniofacial cartilage repair.

Adipose-derived mesenchymal stem cell-incorporated PLLA porous microspheres for cartilage regeneration.

BACKGROUND: In facial plastic surgery, patients with nasal deformity are often treated by rib cartilage transplantation. In recent years, cartilage tissue engineering has developed as an alternative to complex surgery for patients with minor nasal defects via injection of nasal filler material. In this study, we prepared an injectable nasal filler material containing poly-L-lactic acid (PLLA) porous microspheres (PMs), hyaluronic acid (HA) and adipose-derived mesenchymal stem cells (ADMSCs). METHODS: We seeded ADMSCs into as-prepared PLLA PMs using our newly invented centrifugation perfusion technique. Then, HA was mixed with ADMSC-incorporated PLLA PMs to form a hydrophilic and injectable cell delivery system (ADMSC-incorporated PMH). RESULTS: We evaluated the biocompatibility of PMH in vitro and in vivo. PMH has good injectability and provides a favorable environment for the proliferation and chondrogenic differentiation of ADMSCs. In vivo experiments, we observed that PMH has good biocompatibility and cartilage regeneration ability. CONCLUSION: In this study, a injectable cell delivery system was successfully constructed. We believe that PMH has potential application in cartilage tissue engineering, especially in nasal cartilage regeneration.

A deep learning-based automatic image quality assessment method for respiratory phase on computed tomography chest images.

Background: Computed tomography (CT) chest scans have become commonly used in clinical diagnosis. Image quality assessment (IQA) for CT images plays an important role in CT examination. It is worth noting that IQA is still a manual and subjective process, and even experienced radiologists make mistakes due to human limitations (fatigue, perceptual biases, and cognitive biases). There are also kinds of biases because of poor consensus among radiologists. Excellent IQA methods can reliably give an objective evaluation result and also reduce the workload of radiologists. This study proposes a deep learning (DL)-based automatic IQA method, to assess whether the image quality of respiratory phase on CT chest images are optimal or not, so that the CT chest images can be used in the patient's physical condition assessment. Methods: This retrospective study analysed 212 patients' chest CT images, with 188 patients allocated to a training set (150 patients), validation set (18 patients), and a test set (20 patients). The remaining 24 patients were used for the observer study. Data augmentation methods were applied to address the problem of insufficient data. The DL-based IQA method combines image selection, tracheal carina segmentation, and bronchial beam detection. To automatically select the CT image containing the tracheal carina, an image selection model was employed. Afterward, the area-based approach and score-based approach were proposed and used to further optimize the tracheal carina segmentation and bronchial beam detection results, respectively. Finally, the score about the image quality of the patient's respiratory phase images given by the DL-based automatic IQA method was compared with the mean opinion score (MOS) given in the observer study, in which four blinded experienced radiologists took part. Results: The DL-based automatic IQA method achieved good performance in assessing the image quality of the respiratory phase images. For the CT sequence of the same patient, the DL-based IQA method had an accuracy of 92% in the assessment score, while the radiologists had an accuracy of 88%. The Kappa value of the assessment score between the DL-based IQA method and radiologists was 0.75, with a sensitivity of 85%, specificity of 91%, positive predictive value (PPV) of 92%, negative predictive value (NPV) of 93%, and accuracy of 88%. Conclusions: This study develops and validates a DL-based automatic IQA method for the respiratory phase on CT chest images. The performance of this method surpassed that of the experienced radiologists on the independent test set used in this study. In clinical practice, it is possible to reduce the workload of radiologists and minimize errors caused by human limitations.

Omics-based construction of regulatory variants can be applied to help decipher pig liver-related traits.

Genetic variants can influence complex traits by altering gene expression through changes to regulatory elements. However, the genetic variants that affect the activity of regulatory elements in pigs are largely unknown, and the extent to which these variants influence gene expression and contribute to the understanding of complex phenotypes remains unclear. Here, we annotate 90,991 high-quality regulatory elements using acetylation of histone H3 on lysine 27 (H3K27ac) ChIP-seq of 292 pig livers. Combined with genome resequencing and RNA-seq data, we identify 28,425 H3K27ac quantitative trait loci (acQTLs) and 12,250 expression quantitative trait loci (eQTLs). Through the allelic imbalance analysis, we validate two causative acQTL variants in independent datasets. We observe substantial sharing of genetic controls between gene expression and H3K27ac, particularly within promoters. We infer that 46% of H3K27ac exhibit a concomitant rather than causative relationship with gene expression. By integrating GWAS, eQTLs, acQTLs, and transcription factor binding prediction, we further demonstrate their application, through metabolites dulcitol, phosphatidylcholine (PC) (16:0/16:0) and published phenotypes, in identifying likely causal variants and genes, and discovering sub-threshold GWAS loci. We provide insight into the relationship between regulatory elements and gene expression, and the genetic foundation for dissecting the molecular mechanism of phenotypes.

A silk-based hydrogel containing dexamethasone and lipoic acid microcrystals for local delivery to the inner ear.

Local drug delivery has been exploited recently to treat hearing loss, as this method can both bypass the blood-labyrinth barrier and provide sustained drug release. Combined drug microcrystals (MCs) offer additional advantages for sensorineural hearing loss treatment via intratympanic (IT) injection due to their shape effect and combination strategy. In this study, to endow viscous effects of hydrogels, nonspherical dexamethasone (DEX) and lipoic acid (LA) MCs were incorporated into silk fibroin (SF) hydrogels, which were subsequently administered to the tympanic cavity to investigate their pharmaceutical properties. First, we prepared DEX and LA MCs by a traditional precipitation technique followed by SF hydrogel incorporation (SF+DEX+LA). After characterization of the physicochemical features, including morphology, rheology, and dissolution, both a suspension of combined DEX and LA MCs (DEX+LA) and SF+DEX+LA were administered to guinea pigs by IT injection, after which the pharmacokinetics, biodegradation and biocompatibility were evaluated. To our surprise, compared to the DEX+LA group, the pharmacokinetics of the SF+DEX+LA hydrogel group did not improve significantly, which may be ascribed to their nonspherical shape and deposition effects of the drugs MCs. The cochlear tissue in each group displayed good morphology, with no obvious inflammatory reactions. This combined MC suspension has the clear advantages of no vehicle, easy scale-up preparation, and good biocompatibility and outcomes, which paves the way for practical treatment of hearing loss via local drug delivery.

The effects of stiffness on the specificity and avidity of antibody-coated microcapsules with target cells are strongly shape dependent.

Antibody modification is a common method for endowing drug carriers with the ability to target specific cells. Recent studies suggest that the efficacy of these antibody-modified drug carriers is closely related to their physicochemical properties, such as size, shape, stiffness, charge, and surface chemistry. In this study, we functionalized microcapsules with antibodies to investigate the combined effect of shape and stiffness on their targeting ability. We synthesized hollow microcapsules, both spherical and rod-shaped, with adjustable stiffness using calcium carbonate particles as templates and silk fibroin (SF) as the shell material. These microcapsules were then functionalized with trastuzumab (TTZ) to enhance targeting capabilities. Our analysis revealed that increasing stiffness significantly improved the specificity and avidity of TTZ-coated rod-shaped microcapsules, but not spherical ones, indicating a strong shape-dependent influence of stiffness on these properties. Additionally, we explored the mechanisms of endocytosis using various inhibitors and found that both macropinocytosis and clathrin played critical roles in the cellular uptake of microcapsules. Furthermore, we loaded microcapsules with doxorubicin (DOX) to evaluate their anti-tumor efficacy. The stiffest TTZ-coated, DOX-loaded rod-shaped microcapsules demonstrated the most potent anti-tumor effects on BT-474 cells and the highest uptake in BT-474 3D spheroids. This research contributes to the development of more effective microcapsule-based target delivery systems and the realization of the full potential of microcapsule drug delivery systems.

Pig H3K4me3, H3K27ac, and gene expression profiles reveal reproductive tissue-specific activity of transposable elements.

Regulatory sequences and transposable elements (TEs) account for a large proportion of the genomic sequences of species; however, their roles in gene transcription, especially tissue-specific expression, remain largely unknown. Pigs serve as an excellent animal model for studying genomic sequence biology due to the extensive diversity among their wild and domesticated populations. Here, we conducted an integrated analysis using H3K27ac ChIP-seq, H3K4me3 ChIP-seq, and RNA-seq data from 10 different tissues of seven fetuses and eight closely related adult pigs. We aimed to annotate the regulatory elements and TEs to elucidate their associations with histone modifications and mRNA expression across different tissues and developmental stages. Based on correlation analysis between mRNA expression and H3K27ac and H3K4me3 peak activity, results indicated that H3K27ac exhibited stronger associations with gene expression than H3K4me3. Furthermore, 1.45% of TEs overlapped with either the H3K27ac or H3K4me3 peaks, with the majority displaying tissue-specific activity. Notably, a TE subfamily (LTR4C_SS), containing binding motifs for SIX1 and SIX4, showed specific enrichment in the H3K27ac peaks of the adult and fetal ovaries. RNA-seq analysis also revealed widespread expression of TEs in the exons or promoters of genes, including 4 688 TE-containing transcripts with distinct development stage-specific and tissue-specific expression. Of note, 1 967 TE-containing transcripts were enriched in the testes. We identified a long terminal repeat (LTR), MLT1F1, acting as a testis-specific alternative promoter in SRPK2 (a cell cycle-related protein kinase) in our pig dataset. This element was also conserved in humans and mice, suggesting either an ancient integration of TEs in genes specifically expressed in the testes or parallel evolutionary patterns. Collectively, our findings demonstrate that TEs are deeply embedded in the genome and exhibit important tissue-specific biological functions, particularly in the reproductive organs.

Toxicity and chemical characterization of shale gas wastewater discharged to the receiving water: Evidence from toxicity identification evaluation.

Flowback and produced water (FPW) generated from shale gas extraction is a complex mixture consisting of injected drilling fluid, deep formation water, and byproducts of downhole reactions. Limited knowledge is available regarding the impact of discharged FPW on surface water in China. With the development of shale gas exploitation, this emphasizes an urgent need for comprehensive assessments and stringent regulations to ensure the safe disposal of shale gas extraction-related wastewater. Herein, we explored potential impacts of treated shale gas wastewater discharged into a local river in southwest China through toxicity identification evaluation (TIE). Results revealed that organics and particulates significantly contributed to the overall toxicity of the treated FPW wastewater. Through target and suspect chemical analyses, various categories of organic contaminants were detected, including alkanes, aromatic hydrocarbons, biocides, phenols, and phthalates. Furthermore, non-target analysis uncovered the presence of surfactant-related contaminants in tissues of exposed organisms, but their contribution to the observed toxicity was unclear due to the lack of effect data for these compounds. Higher toxicity was found at the discharge point compared with upstream sites; however, the toxicity was rapidly mitigated due to dilution in the receiving river, posing little impact on downstream areas. Our study highlighted the importance of monitoring toxicity and water quality of FPW effluent even though dilution could be a viable approach when the water volume in the discharge was small.

Deep learning-driven multi-view multi-task image quality assessment method for chest CT image.

BACKGROUND: Chest computed tomography (CT) image quality impacts radiologists' diagnoses. Pre-diagnostic image quality assessment is essential but labor-intensive and may have human limitations (fatigue, perceptual biases, and cognitive biases). This study aims to develop and validate a deep learning (DL)-driven multi-view multi-task image quality assessment (M[Formula: see text]IQA) method for assessing the quality of chest CT images in patients, to determine if they are suitable for assessing the patient's physical condition. METHODS: This retrospective study utilizes and analyzes chest CT images from 327 patients. Among them, 1613 images from 286 patients are used for model training and validation, while the remaining 41 patients are reserved as an additional test set for conducting ablation studies, comparative studies, and observer studies. The M[Formula: see text]IQA method is driven by DL technology and employs a multi-view fusion strategy, which incorporates three scanning planes (coronal, axial, and sagittal). It assesses image quality for multiple tasks, including inspiration evaluation, position evaluation, radiation protection evaluation, and artifact evaluation. Four algorithms (pixel threshold, neural statistics, region measurement, and distance measurement) have been proposed, each tailored for specific evaluation tasks, with the aim of optimizing the evaluation performance of the M[Formula: see text]IQA method. RESULTS: In the additional test set, the M[Formula: see text]IQA method achieved 87% precision, 93% sensitivity, 69% specificity, and a 0.90 F1-score. Extensive ablation and comparative studies have demonstrated the effectiveness of the proposed algorithms and the generalization performance of the proposed method across various assessment tasks. CONCLUSION: This study develops and validates a DL-driven M[Formula: see text]IQA method, complemented by four proposed algorithms. It holds great promise in automating the assessment of chest CT image quality. The performance of this method, as well as the effectiveness of the four algorithms, is demonstrated on an additional test set.

Dendronized chitosan hydrogel with GIT1 to accelerate bone defect repair through increasing local neovascular amount.

Bone defects have long been a major healthcare issue because of the difficulties in regenerating bone mass volume and the high cost of treatment. G protein-coupled receptor kinase 2 interacting protein 1 (GIT1) has been proven to play an important role both in vascular development and in bone fracture healing. In this study, a type of thermoresponsive injectable hydrogel from oligoethylene glycol-based dendronized chitosan (G1-CS) was loaded with GIT1-plasmids (G1-CS/GIT1), and used to fill unicortical bone defects. RT-PCR analysis confirmed that G1-CS/GIT1 enhanced DNA transfection in MSCs both in vitro and in vivo. From the results of micro-CT, RT-PCR and histological analysis, it can be concluded that G1-CS/GIT1 accelerated the bone healing rate and increased the amount of neovascularization around the bone defects. In addition, an adeno-associated virus (AAV)-GIT1 was constructed to transfect mesenchymal stem cells. The results of capillary tube formation assay, immunofluorescence staining and western blot analysis proved that high expression of GIT1 induces mesenchymal stem cells to differentiate into endothelial cells. RT-PCR analysis and capillary tube formation assay confirmed that the Notch signaling pathway was activated in the differentiation process. Overall, we developed an efficient strategy through combination of injectable hydrogel and G1T1 for bone tissue engineering.

Toxicity identification evaluation for hydraulic fracturing flowback and produced water during shale gas exploitation in China: Evidence from tissue residues and gene expression.

Hydraulic fracturing flowback and produced water (HF-FPW) from shale gas extraction processes is a highly complex medium with potential threats to the environment. Current research on ecological risks of FPW in China is limited, and the link between major components of FPW and their toxicological effects on freshwater organisms is largely unknown. By integrating chemical and biological analyses, toxicity identification evaluation (TIE) was used to reveal causality between toxicity and contaminants, potentially disentangling the complex toxicological nature of FPW. Here, FPW from different shale gas wells, treated FPW effluent, and a leachate from HF sludge were collected from southwest China, and TIE was applied to obtain a comprehensive toxicity evaluation in freshwater organisms. Our results showed that FPW from the same geographic zone could cause significantly different toxicity. Salinity, solid phase particulates, and organic contaminants were identified as the main contributors to the toxicity of FPW. In addition to water chemistry, internal alkanes, PAHs, and HF additives (e.g., biocides and surfactants) were quantified in exposed embryonic fish by target and non-target tissue analyses. The treated FPW failed to mitigate the toxicity associated with organic contaminants. Transcriptomic results illustrated that organic compounds induced toxicity pathways in FPW-exposed embryonic zebrafish. Similar zebrafish gene ontologies were affected between treated and untreated FPW, again confirming that sewage treatment did not effectively remove organic chemicals from FPW. Thus, zebrafish transcriptome analyses revealed organic toxicant-induced adverse outcome pathways and served as evidence for TIE confirmation in complex mixtures under data-poor scenarios.

Construction of PLGA Porous Microsphere-Based Artificial Pancreatic Islets Assisted by the Cell Centrifugation Perfusion Technique.

Pancreatic islet transplantation is a promising treatment that could potentially reverse diabetes, but its clinical applicability is severely limited by a shortage of organ donors. Various cell loading approaches using polymeric porous microspheres (PMs) have been developed for tissue regeneration; however, PM-based multicellular artificial pancreatic islets' construction has been scarcely reported. In this study, MIN6 (a mouse insulinoma cell line) and MS1 (a mouse pancreatic islet endothelial cell line) cells were seeded into poly(lactic-co-glycolic acid) (PLGA) PMs via an upgraded centrifugation-based cell perfusion seeding technique invented and patented by our group. Cell morphology, distribution, viability, migration, and proliferation were all evaluated. Results from glucose-stimulated insulin secretion (GSIS) assay and RNA-seq analysis suggested that MIN6 and MS1-loaded PLGA PMs exhibited better glucose responsiveness, which is partly attributable to vascular formation during PM-dependent islet construction. The present study suggests that the PLGA PM-based artificial pancreatic islets may provide an alternative strategy for the potential treatment of diabetes in the future.

Numerical Study on the Buckling Behavior of FG Porous Spherical Caps Reinforced by Graphene Platelets.

The buckling response of functionally graded (FG) porous spherical caps reinforced by graphene platelets (GPLs) is assessed here, including both symmetric and uniform porosity patterns in the metal matrix, together with five different GPL distributions. The Halpin-Tsai model is here applied, together with an extended rule of mixture to determine the elastic properties and mass density of the selected shells, respectively. The equilibrium equations of the pre-buckling state are here determined according to a linear three-dimensional (3D) elasticity basics and principle of virtual work, whose solution is determined from classical finite elements. The buckling load is, thus, obtained based on the nonlinear Green strain field and generalized geometric stiffness concept. A large parametric investigation studies the sensitivity of the natural frequencies of FG porous spherical caps reinforced by GPLs to different parameters, namely, the porosity coefficients and distributions, together with different polar angles and stiffness coefficients of the elastic foundation, but also different GPL patterns and weight fractions of graphene nanofillers. Results denote that the maximum and minimum buckling loads are reached for GPL-X and GPL-O distributions, respectively. Additionally, the difference between the maximum and minimum critical buckling loads for different porosity distributions is approximately equal to 90%, which belong to symmetric distributions. It is also found that a high weight fraction of GPLs and a high porosity coefficient yield the highest and lowest effects of the structure on the buckling loads of the structure for an amount of 100% and 12.5%, respectively.

The Effect of Ecological Management on Regional Health Inequality.

Ecological management has been implemented to improve individual well-being. However, it remains unclear whether this management has improved health inequality over time. Aiming to examine whether health inequality is caused by ecological management in China, we harnessed a macro-level dataset from 2001 to 2019 across 31 Chinese provinces-combined with gene and dietary culture data-and utilized a bilateral approach to pair provincial data. Empirical results of system Generalized Method of Moments (sys-GMM) estimations in benchmark and extensive models which suggest a negative and statistically significant causal effect of ecological management on health inequality. Specifically, ecological management contributes to decreasing the inequality in the population death rate, the death rate among pregnant women, the underweight newborn rate, the child malnutrition rate, and the infectious disease mortality. The results are robust to weak instruments in the sys-GMM setting and a delayed effect of ecological management. Additionally, the heterogeneity analysis shows that the causal effect of ecological management on decreasing regional health inequality is more significant and higher for subsamples in identical regions than in different regions.

Intratympanic microcrystals of dexamethasone and lipoic acid for the treatment of cisplatin-induced inner ear injury.

Steroids (anti-inflammatory drugs) combined with antioxidants are frequently prescribed to treat cisplatin (CP)-induced hearing loss in the clinic. Compared to systemic administration of free drugs, local drug delivery systems offer better therapeutic qualities and patient compliance since they not only can bypass the blood-labyrinth barrier but also can perform sustained release. In this work, dexamethasone (DEX) and lipoic acid (LA) non-spherical microcrystals (MCs) were prepared without complicated chemical modification. Following a series of physical characterizations, including morphology, stability and injectability, dissolution and round window membrane distribution of MCs, DEX MCs, LA MCs and the simple mixture of DEX MCs + LA MCs (combination group) were administered in guinea pigs by intratympanic injection. We found that LA MCs enabled improvement of DEX absorption in the combination group compared to a single dose. In addition, no significant morphological changes or inflammatory responses were observed in cochlear tissue, indicating good biocompatibility. Finally, the combination group also demonstrated synergistic therapeutic effect for protecting hair cells against CP-induced damage. The local co delivery of DEX MCs and LA MCs offers a new strategy for the treatment of CP-induced inner ear injury since they provide sustained anti-inflammatory and antioxidant effects simultaneously.