ZNF32 prevents the activation of cancer-associated fibroblasts through negative regulation of TGFB1 transcription in breast cancer.

Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancer-related deaths in women worldwide. Cancer-associated fibroblasts (CAFs) are one of the fundamental cellular components of the tumor microenvironment and play a critical role in the initiation, progression, and therapy resistance of breast cancer. However, the detailed molecular mechanisms of CAFs activation from normal fibroblasts (NFs) are still not well understood. In the present study, we reported that ZNF32 expression in breast cancer cells was negatively correlated with CAF-related markers (FSP1, α-SMA, and FAP) in stromal fibroblasts, and loss of ZNF32 promoted the activation of CAFs, as evidenced by the enhanced proliferation and contractility of CAFs. ZNF32 deficiency-mediated fibroblast activation promoted the growth and metastasis of breast cancer cells in vitro and in vivo. Mechanistically, we demonstrated that ZNF32 inhibited TGFB1 transcription by directly binding to the -1968/-1962 region of the TGFB1 promoter, leading to the prevention of fibroblast activation. Altogether, our findings reveal an important mechanism by which ZNF32 suppression increases the transcription of the TGFB1 gene in breast cancer cells, and subsequently, elevated levels of secretory TGF-ß stimulate NFs transformation into CAFs, which in turn facilitates the malignant progression of breast cancer. Our data implicated ZNF32 as a potential therapeutic strategy against breast cancer.

The small GTPase Ypt7 of Penicillium expansum is required for growth, patulin biosynthesis and virulence.

Ypt GTPases are the largest subfamily of small GTPases involved in membrane transport. Here, a PeYpt7 gene deletion mutant of P. expansum was constructed. The ΔPeYpt7 mutant showed reduced colony growth with abnormal mycelial growth, reduced conidiation, and insufficient spore development. The mutation rendered the pathogen susceptible to osmotic stress and cell wall stressors. In addition, the absence of PeYpt7 reduced patulin production in P. expansum and significantly limited gene expression (PatG, PatH, PatI, PatD, PatF, and PatL). In addition, the mutant showed attenuated virulence in infected fruit and reduced expression of pathogenic factors was (PMG, PG, PL, and GH1). Thus, PeYpt7 modulates the growth, morphology, patulin accumulation, and pathogenicity of P. expansum by limiting the expression of related genes.

The pH signalling transcription factor PacC modulate growth, development, stress response and pathogenicity of Trichothecium roseum.

pH is one of the important environmental factors that affect the growth, development and pathogenicity of postharvest pathogen. The transcription factor PacC dominates the pH signal pathway. PacC in Trichothecium roseum showed three typical conserved zinc finger domains and closest homology to Fusarium graminearum. T. roseum increased the environmental pH both in vitro and in vivo. Expression patterns of TrpacC under different pH showed that at increasing pH from 3 to 5, the wild-type (WT) strain induced the expression of TrPacC in parallel to increased fungal growth; however, TrPacC expression decline at higer pH than 5, while fungal growth continued to increase. Development of a ΔTrPacC mutant down-regulated the expression of TrbrlA, TrabaA and TrwetA, reduced sporulation and delayed spore germination, resulting in smaller spores and sparse hyphae. ΔTrPacC mutant was sensitive to ionic stress, oxidative stress and cell wall integrity stress compared to the WT strain, especially the ionic stress. In addition, ∆TrPacC mutant showed reduced pathogenicity to muskmelon and tomato fruits. Taken together, T. roseum is an alkalinizing fungus, and the acidic environment could induce TrPacC expression. TrPacC positively regulates fungal growth and development as well as pathogenicity showing effect on fungal response to different stresses.

Deep learning-based detection and stage grading for optimising diagnosis of diabetic retinopathy.

AIMS: To establish an automated method for identifying referable diabetic retinopathy (DR), defined as moderate nonproliferative DR and above, using deep learning-based lesion detection and stage grading. MATERIALS AND METHODS: A set of 12,252 eligible fundus images of diabetic patients were manually annotated by 45 licenced ophthalmologists and were randomly split into training, validation, and internal test sets (ratio of 7:1:2). Another set of 565 eligible consecutive clinical fundus images was established as an external test set. For automated referable DR identification, four deep learning models were programmed based on whether two factors were included: DR-related lesions and DR stages. Sensitivity, specificity and the area under the receiver operating characteristic curve (AUC) were reported for referable DR identification, while precision and recall were reported for lesion detection. RESULTS: Adding lesion information to the five-stage grading model improved the AUC (0.943 vs. 0.938), sensitivity (90.6% vs. 90.5%) and specificity (80.7% vs. 78.5%) of the model for identifying referable DR in the internal test set. Adding stage information to the lesion-based model increased the AUC (0.943 vs. 0.936) and sensitivity (90.6% vs. 76.7%) of the model for identifying referable DR in the internal test set. Similar trends were also seen in the external test set. DR lesion types with high precision results were preretinal haemorrhage, hard exudate, vitreous haemorrhage, neovascularisation, cotton wool spots and fibrous proliferation. CONCLUSIONS: The herein described automated model employed DR lesions and stage information to identify referable DR and displayed better diagnostic value than models built without this information.

Shape-programmable magneto-active elastomer composites for curve and biomimetic behavior imitation.

A programming methodology, which can be applied to soft-magnetic-material-based magneto-active elastomers (MAEs), to catch the predefined specific objective curves is proposed in this study. The objective curves have been equally separated into a couple of segments, which will be filled by the designed MAE elements. Furthermore, the designed MAE segments with different chain angles, in which the deformation orientation of each element under applied homogeneous magnetic fields has been investigated based on the designed experimental setup, are arrayed based on the proposed programming methodology to constitute the MAE composite to catch the orientation of the objective curve. The experimental results show that based on the proposed programming methodology, the MAE composites can describe different curves, which include harmonic, tangential and arc tangential functions under applied homogeneous magnetic fields with good agreement. Furthermore, on the basis of the proposed programming methodology, the MAE composites are utilized to mimic the typical biomimetic behavior (the peeking-up behavior of snakes and the flapping behavior of birds) with smooth curvature properties, in which the dynamic procedures present continuous curves.

Pandemic and bank lending: Evidence from the 2009 H1N1 pandemic.

This paper empirically analyzes the impact of pandemic on the contracting of bank loans. Using data on syndicated loans during the season of H1N1 Swine Flu, we find that more flu is associated with higher loan spreads and smaller loan size. The adverse impact of pandemic was alleviated by the approval of vaccines.

Ephedrine causes retinal damage in SD rats associating with JAK2/STAT3 pathway.

PURPOSE: Ephedrine has various side effects in the cardiovascular and nervous systems. However, the cellular mechanism of toxicity remains unknown, specifically on the retina. This study was to investigate effects of ephedrine on the retina and explore the underlying mechanisms. METHODS: Sprague Dawley rats were treated with ephedrine (n = 10) or saline (n = 10) by oral gavage for seven days. The retinal morphology was evaluated by Toluidine blue staining. Apoptosis-related markers were detected in the retinal lysate. Enzyme-linked immunosorbent assays were used to measure neurotransmitters and oxidative stress markers. Real-time PCR and western blot were used to measure gene and protein expression, respectively. RESULTS: Our results demonstrated that ephedrine induced apoptosis in the retina, increased dopamine level as well as oxidative stress, and down-regulated the Jak2/Stat3 gene expression as well as protein expression of p-JAK2/p-STAT3. CONCLUSIONS: Our study indicated that ephedrine treatment caused retinal damage in SD rats, which may be associated with the JAK2/STAT3 pathway.

[Decomposition of X-Ray Fluorescence Overlapping Peaks Based on Statistical and Genetic Algorithms].

In fluorescence analysis, the phenomenon of overlapping often occurs among adjacent peaks. In the view of the random physical properties of formation process of X fluorescence spectra, Gaussian Mixture Statistics Model (GMSM) and Genetic Algorithms were used for the decomposition of overlapping peaks. First, the GMSM was proposed to describe the overlapping peaks, and the local convergence problem of expectation maximization (EM) was analyzed. Secondly, the GMSM parameters were regarded as individual genes, and the log-likelihood function of overlapping peaks random data was set as fitness function. A fast algorithm for the objective function value was proposed. Finally, the population search technology of Genetic Algorithm was used to find the global optimal solution, and to realize the decomposition of overlapping peaks. All measured data were regarded as "useful" data. The "useful" degree was reflected by their probability. The GMSM method can achieve the "best match" effect in the maximum global probability with zero loss of original data, which can fit the random of radiation measurement process. The decomposition experiments of four serious overlapping peaks show high precision of the peak position, peak area and standard deviation. The maximum error was 0.7 channel, 2.3% and 2.17%, respectively, which is especially suitable for the condition of serious overlap and can be widely used for the decomposition of other energy spectrum.

Causes and management strategies for elevated intraocular pressure after implantable collamer lens implantation.

With the widespread application of Implantable Collamer Lens (ICL) implantation surgery in the field of myopia correction, a comprehensive understanding of its potential complications, especially those related to intraocular pressure (IOP), becomes crucial. This article systematically reviews various complications that may lead to IOP elevation after ICL surgery. Firstly, common complications after ICL surgery, including residual viscoelastic, steroid response, and excessive vault of the ICL, are detailed, emphasizing their potential impact on intraocular pressure. Regarding residual viscoelastic, we delve into its direct relationship with postoperative elevated IOP and possible preventive measures. For steroid response, we stress the importance of timely adjustment of steroid therapy and monitoring intraocular pressure. Additionally, excessive vault of the ICL is considered a significant potential issue, and we elaborate on its mechanism and possible management methods. In further discussion, we focus on relatively rare complications such as Toxic Anterior Segment Syndrome (TASS), Urrets-Zavalia Syndrome (UZS), Pigment Dispersion Syndrome (PDS), and malignant glaucoma. For these relatively rare complications, this review thoroughly explores their potential mechanisms, emphasizes the importance of prevention, and provides guidance for early diagnosis and treatment. This is a comprehensible review that aims to offer eye care professionals a comprehensive understanding and effective management guidance for complications of elevated IOP after ICL surgery, ultimately providing optimal care for patients' visual health.

Markers of intestinal barrier damage in patients with chronic insomnia disorder.

Objective: Insomnia disorder stands out as one of the prevalent clinical sleep and psychiatric disorders. Prior research has unequivocally demonstrated variations in the diversity and abundance of gut microbiota among individuals with insomnia disorder. These alterations may play a direct or indirect role in the onset and progression of insomnia disorder by compromising the integrity of the intestinal barrier. This study aims to evaluate the impairment of the intestinal barrier in individuals with insomnia disorder by scrutinizing the serum functionality of this barrier. Materials and methods: 45 patients with chronic insomnia disorder and 30 matched healthy volunteers were meticulously selected based on inclusion criteria. ELISA technology was employed to measure serum levels of diamine oxidase (DAO), D-lactic acid (D-LA), intestinal fatty acid binding protein (I-FABP), and endothelin (ET). Spearman correlation analysis was used to explore the relationship between intestinal mucosal markers and clinical characteristics. Data were analyzed using SPSS 26.0. Results: Compared to the healthy control group, the insomnia disorder group exhibited significantly elevated scores on subjective mood and sleep scales (GAD-7, PHQ-9, HAMA, HAMD, PSQI, and ISI) (P < 0.05). Overnight PSG indicated a notable increase in bed time, total wake time, sleep onset latency, and wake after sleep onset in individuals with insomnia disorder. Additionally, there was a decrease in sleep efficiency and alterations in sleep structure (increased proportion of N1 and N3 stages, prolonged N1 stage) (P < 0.05). The chronic insomnia disorder group displayed significantly reduced concentrations of serum DAO, D-LA, I-FABP, and ET (P < 0.05). Furthermore, significant positive correlations were identified between intestinal epithelial barrier markers and sleep efficiency, while negative correlations were found with wake after sleep onset, total wake time, PSQI, HAMA, and HAMD. Additionally, D-LA levels were significantly positively correlated with ET concentrations. Conclusion: Individuals with chronic insomnia disorder manifest disruptions in sleep structure, heightened susceptibility to anxiety and depressive moods, and impaired intestinal barrier function. These findings suggest that the occurrence and development of insomnia disorder may be linked to the impairment of the intestinal barrier.

Moldy odors in food - a review.

Food products are susceptible to mold contamination, releasing moldy odors. These moldy odors not only affect the flavor of food, but also pose a risk to human health. Moldy odors are a mixture of volatile organic compounds (VOCs) released by the fungi themselves, which are the main source of moldy odors in moldy foods. These VOCs are secondary metabolites of fungi and are synthesized through various biosynthetic pathways. Both the fungi themselves and environmental factors affect the release of moldy odors. This review summarized the main components of musty odors in moldy foods and their producing fungi. In addition, this review focused on the functions of moldy volatile organic compounds (MVOCs) and the biosynthetic pathways of the major MVOCs, and summarized the factors affecting the release of MVOCs as well as the detection methods. It expected to provide a basis for ensuring food safety.

Preharvest spraying of phenylalanine activates the sucrose and respiratory metabolism in muskmelon wounds during healing.

Phenylalanine (Phe) accelerates fruit wound healing by activating phenylpropanoid metabolism. However, whether Phe affects sucrose and respiratory metabolism in fruit during wound healing remains unknown. In this research, we found that preharvest Phe spray promoted sucrose degradation and increased glucose and fructose levels by activating acid invertase (AI), neutral invertase (NI), sucrose synthase (SS) and sucrose phosphate synthase (SPS) on harvested muskmelons. The spray also activated hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), malate dehydrogenase (MDH), succinate dehydrogenase (SDH) and glucose-6-phosphate dehydrogenase (G6PDH). In addition, the spray improved energy and reducing power levels in the fruit. Taken together, preharvest Phe spray can provide carbon skeleton, energy and reducing power for wound healing by activating the sucrose metabolism, Embden-Meyerhof-Parnas (EMP) pathway, tricarboxylic acid (TCA) cycle and pentose phosphate (PPP) pathway in muskmelon wounds during healing, which is expected to be developed as a new strategy to accelerate fruit wound healing.

From inception to innovation: bibliometric analysis of the evolution, hotspots, and trends in implantable collamer lens surgery research.

Background: As one of several refractive surgeries, Implant Collamer Lens (ICL) surgery offers stable biocompatibility and consistent, high-quality visual outcomes. ICL has become an effective complement to corneal refractive surgery, gradually becoming one of the mainstream methods for correcting refractive errors. This study employs bibliometric methods to analyze research on ICL surgery to understand the progress, hotspots, and potential future trends in this field. Methods: This study performed a bibliometric analysis of all ICL-related articles collected from the Web of Science Core Collection database between January 1st, 1996, and December 31st, 2023. The CiteSpace 6.2.R4 tool, Excel and the Web of Science website were used to analyze data by country, institution, keywords, and clusters of keywords. Additionally, an in-depth interpretation and analysis were conducted on the field's high-impact articles. Results: Since the first clinical application report of ICL, there have been a total of 875 studies. The number of papers published annually has shown an overall increasing trend. Studies published from China are the most numerous, accounting for 29.14% (n = 255) of the total. Among the institutions, Fudan University and Kitasato University both have published more than 50 papers, with Kitasato University having the highest H-index of 26. The journals with the top 10 publication volumes are all specialized in ophthalmology. The burst keywords since the introduction of ICL surgery have been "intraocular lens," "refractive surgery," and "cataract surgery." The current burst keywords include "visual quality," "vector analysis," "axial length," etc. The results of keyword clustering included ICL, pIOL, high myopia, axial length, optical quality, refractive surgery, ICL implantation, and pupil size. In the High-impact Articles, it was found that the high-impact articles predominantly focus on the safety, efficacy, and predictability of ICL surgery. Conclusion: Research on ICL has grown since its clinical introduction, with the advent of the central hole ICL sparking a surge in recent hotspots, particularly in China. Current hotpots in the field of ICL surgery are "visual quality," "ICL implantation," "vector analysis," "axial length," "evo ICL," "ICL v4c," and "ICL." ICL surgery research trends have evolved from implantation techniques to biological parameters associated with ICL surgery and the benefits of new ICL designs.

Regulation of sucrose metabolism, sugar transport and pentose phosphate pathway by PacC in apple fruit colonized by Penicillium expansum.

A critical transcription factor, PacC, modulates the expression of fungal pH signaling. Although PacC-mediated environmental pH has been reported to regulate the growth and pathogenicity of postharvest pathogens, the involvement of PacC in sucrose metabolism, sugar transport, and the pentose phosphate pathway (PPP) in different zones of decayed fruit remains unclear. Our work showed that the inoculation with a PePacC deletion strain of Penicillium expansum (ΔPePacC) accelerated sucrose catabolism and glucose and fructose accumulation in different zones of apple fruit. This was attributed to an increase in sucrose metabolism enzyme activities and up-regulation of the sugar transporter protein-related gene expression. Moreover, ΔPePacC inoculation increased the PPP-related enzyme activities and the levels of nicotinamide adenine dinucleotide phosphate (NADPH) and NADP+. In conclusion, PacC modulates sucrose metabolism, sugar transport, and the PPP in apple fruit by mediating dynamic changes in environmental pH, thereby enhancing fruit disease resistance.

Exploring the causal relationship between body mass index and keratoconus: a Mendelian randomization study.

Background: Despite reports suggesting a link between obesity and keratoconus, the causal relationship is not fully understood. Methods: We used genome-wide association study (GWAS) data from public databases for a two-sample Mendelian randomization analysis to investigate the causal link between body mass index (BMI) and keratoconus. The primary method was inverse variance weighted (IVW), complemented by different analytical techniques and sensitivity analyses to ensure result robustness. A meta-analysis was also performed to bolster the findings' reliability. Results: Our study identified a significant causal relationship between BMI and keratoconus. Out of 20 Mendelian randomization (MR) analyses conducted, 9 showed heterogeneity or pleiotropy. Among the 11 analyses that met all three MR assumptions, 4 demonstrated a significant causal difference between BMI and keratoconus, while the remaining 7 showed a positive trend but were not statistically significant. Meta-analysis confirmed a significant causal relationship between BMI and keratoconus. Conclusion: There is a significant causal relationship between BMI and keratoconus, suggesting that obesity may be a risk factor for keratoconus.

Mendelian randomization reveals that abnormal lipid metabolism mediates the causal relationship between body mass index and keratoconus.

Previous studies suggest that a high body mass index (BMI) may be a risk factor for keratoconus (KC), but the causal relationship remains unclear. This study used Mendelian randomization (MR) to investigate this connection and explore the mediating role of circulating serum metabolites and inflammatory factors in this association. Two-sample MR analysis was conducted to assess the relationship between BMI and KC. The study employed a two-step MR approach to evaluate the mediating roles of 91 inflammatory markers and 249 serum metabolites in the BMI-KC relationship. Inverse variance weighting (IVW) was the primary method, and multiple sensitivity analyses were performed to ensure robustness. IVW analysis revealed a positive causal relationship between BMI and KC (OR IVW = 1.811, 95% CI 1.005-3.262, P = 0.048). Although IL-12ß and IL-4 were causally associated with KC, they did not mediate the BMI-KC relationship. Five serum metabolites were identified as potential mediators, with HDL cholesterol and triglyceride ratios showing significance. This study clarified the causal relationship between high BMI and KC, suggesting that high BMI may induce KC through lipid metabolism abnormalities. These findings underscore the importance of managing BMI for KC prevention.

Analysis and comparison of retinal vascular parameters under different glucose metabolic status based on deep learning.

AIM: To develop a deep learning-based model for automatic retinal vascular segmentation, analyzing and comparing parameters under diverse glucose metabolic status (normal, prediabetes, diabetes) and to assess the potential of artificial intelligence (AI) in image segmentation and retinal vascular parameters for predicting prediabetes and diabetes. METHODS: Retinal fundus photos from 200 normal individuals, 200 prediabetic patients, and 200 diabetic patients (600 eyes in total) were used. The U-Net network served as the foundational architecture for retinal artery-vein segmentation. An automatic segmentation and evaluation system for retinal vascular parameters was trained, encompassing 26 parameters. RESULTS: Significant differences were found in retinal vascular parameters across normal, prediabetes, and diabetes groups, including artery diameter (P=0.008), fractal dimension (P=0.000), vein curvature (P=0.003), C-zone artery branching vessel count (P=0.049), C-zone vein branching vessel count (P=0.041), artery branching angle (P=0.005), vein branching angle (P=0.001), artery angle asymmetry degree (P=0.003), vessel length density (P=0.000), and vessel area density (P=0.000), totaling 10 parameters. CONCLUSION: The deep learning-based model facilitates retinal vascular parameter identification and quantification, revealing significant differences. These parameters exhibit potential as biomarkers for prediabetes and diabetes.

Bio-inspired magnetic-driven folded diaphragm for biomimetic robot.

Functional soft materials, exhibiting multiple types of deformation, have shown their potential/abilities to achieve complicated biomimetic behaviors (soft robots). Inspired by the locomotion of earthworm, which is conducted through the contraction and stretching between body segments, this study proposes a type of one-piece-mold folded diaphragm, consisting of the structure of body segments with radial magnetization property, to achieve large 3D and bi-directional deformation with inside-volume change capability subjected to the low homogeneous magnetically driving field (40 mT). Moreover, the appearance based on the proposed magnetic-driven folded diaphragm is able to be easily customized to desired ones and then implanted into different untethered soft robotic systems as soft drivers. To verify the above points, we design the diaphragm pump providing unique properties of lightweight, powerful output and rapid response, and the soft robot including the bio-earthworm crawling robot and swimming robot inspired by squid to exhibit the flexible and rapid locomotion excited by single homogeneous magnetic fields.

Meta-Analysis of the Effect of Nitric Oxide Application on Heavy Metal Stress Tolerance in Plants.

Substantial single-species studies have reported the facility of nitric oxide (NO) in alleviating heavy metal-induced stress in plants. Understanding the mechanisms of NO-involved stress alleviation is progressing; however, a quantitative description of the alleviative capacity of NO against heavy metal stress is still lacking. We combined the results of 86 studies using meta-analysis to statistically assess the responses of heavy metal-stressed plants to NO supply across several metal stresses and plant families. The results showed that plant biomass was consistently improved following NO supply to metal-stressed plants. NO played an important role in mitigating oxidative damage caused by heavy metal stress by significantly stimulating the activities of antioxidant enzymes. Moreover, NO supply consistently increased the Ca, Fe, and Mg contents in both leaves and roots. Plant tissues accumulated less heavy metals when exposed to heavy metal stress after NO addition. Additionally, the best concentration of SNP (an NO donor) for hydroponic culture is in the range of 75-150 µM. We further confirmed that NO application can generally alleviate plant heavy metal stress and its action pathway. The results presented here can help guide future applications of NO as a plant growth regulator in agriculture and breeding plants for heavy metal stress tolerance.

Case report: A de novo NSD2 truncating variant in a child with Rauch-Steindl syndrome.

Wolf-Hirschhorn syndrome (WHS) is a rare genetic disorder caused by a heterozygous deletion on chromosome 4p16.3, which is called the WHS critical region (WHSC). The major features of this disorder, including "Greek warrior helmet" facies, delayed growth, intellectual disability, seizures, and skeletal abnormalities, are caused by the combined haploinsufficiency of multiple genes. The WHS candidate 1 (WHSC1) gene, also known as NSD2, is located in the WHSC and has been reported to associate with Rauch-Steindl syndrome (RSS,OMIM 619695). RSS is a highly heterogeneous disease characterized by mild developmental delay, prenatal-onset growth restriction, low body mass index, and characteristic facial features distinct from WHS. In this report, using whole exome sequencing (WES), we identified a novel de novo heterozygous NSD2 truncating variant in a 7-year-old Chinese girl with Rauch-Steindl syndrome, including failure to thrive, facial dysmorphisms, developmental delay, intellectual disability, and hypotonia. These findings further support that haploinsufficiency of NSD2 is necessary for WHS, and molecular genetic testing is more accurate to diagnose these patients. The novel variant uncovered in this study further expands the mutation spectrum of NSD2.