Multiplatform tear proteomic profiling reveals novel non-invasive biomarkers for diabetic retinopathy.

OBJECTIVES: To investigate a comprehensive proteomic profile of the tear fluid in patients with diabetic retinopathy (DR) and further define non-invasive biomarkers. METHODS: A cross-sectional, multicentre study that includes 46 patients with DR, 28 patients with diabetes mellitus (DM), and 30 healthy controls (HC). Tear samples were collected with Schirmer strips. As for the discovery set, data-independent acquisition mass spectrometry was used to characterize the tear proteomic profile. Differentially expressed proteins between groups were identified, with gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis further developed. Classifying performance of biomarkers for distinguishing DR from DM was compared by the combination of three machine-learning algorithms. The selected biomarker panel was tested in the validation cohort using parallel reaction monitoring mass spectrometry. RESULTS: Among 3364 proteins quantified, 235 and 88 differentially expressed proteins were identified for DR when compared to HC and DM, respectively, which were fundamentally related to retina homeostasis, inflammation and immunity, oxidative stress, angiogenesis and coagulation, metabolism, and cellular adhesion processes. The biomarker panel consisting of NAD-dependent protein deacetylase sirtuin-2 (SIR2), amine oxidase [flavin-containing] B (AOFB), and U8 snoRNA-decapping enzyme (NUD16) exhibited the best diagnostic performance in discriminating DR from DM, with AUCs of 0.933 and 0.881 in the discovery and validation set, respectively. CONCLUSIONS: Tear protein dysregulation is comprehensively revealed to be associated with DR onset. The combination of tear SIR2, AOFB, and NUD16 can be a novel potential approach for non-invasive detection or pre-screening of DR. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2100054263. https://www.chictr.org.cn/showproj.html?proj=143177 . Date of registration: 2021/12/12.

Revealing new insights: Two-center evidence of microplastics in human vitreous humor and their implications for ocular health.

Microplastics (MPs), an emerging environmental contaminant, have raised growing health apprehension due to their detection in various human biospecimens. Despite extensive research into their prevalence in the environment and the human body, the ramifications of their existence within the enclosed confines of the human eye remain largely unexplored. Herein, we assembled a cohort of 49 patients with four ocular diseases (macular hole, macular epiretinal membrane, retinopathy and rhegmatogenous retinal detachment) from two medical centers. After processing the samples with an optimized method, we utilized Laser Direct Infrared (LD-IR) spectroscopy and Pyrolysis Gas Chromatography/Mass Spectrometry (Py-GC/MS) to analyze 49 vitreous samples, evaluating the characteristics of MPs within the internal environment of the human eye. Our results showed that LD-IR scanned a total of 8543 particles in the composite sample from 49 individual vitreous humor samples, identifying 1745 as plastic particles, predominantly below 50 µm. Concurrently, Py-GC/MS analysis of the 49 individual samples corroborated these findings, with nylon 66 exhibiting the highest content, followed by polyvinyl chloride, and detection of polystyrene. Notably, correlations were observed between MP levels and key ocular health parameters, particularly intraocular pressure and the presence of aqueous humor opacities. Intriguingly, individuals afflicted with retinopathy demonstrated heightened ocular health risks associated with MPs. In summary, this research provides significant insights into infiltration of MP pollutants within the human eye, shedding light on their potential implications for ocular health and advocating for further exploration of this emerging health risk.

The siren song of so-called evidence: Why the evidence for social ecology models is not as strong as we think.

Ecological competition models from biology have been adopted for the study of a wide variety of social entities, including workplace organizations and voluntary associations.Despite their popularity, a number of fundamental challenges to these models have not been sufficiently recognized or addressed. As a result, it's possible that some apparently supportive evidence for ecological competition is in fact the outcome of chance or other processes. We propose a permutation test to compare observed evidence for ecological competition against an appropriate counterfactual population. To demonstrate our approach and validate our concern about the quality of evidence for ecological competition models, we apply the permutation test to one specific case. The results indicate that K-correlation values that have been taken as evidence for a well-established model, the Ecology of Affiliation, are quite common even in the absence of ecological competition. We conclude that the existing evidence for social ecology models may not be as reliable as commonly believed due to the disconnect between theory and empirical testing.

Potential Theranostic Roles of SLC4 Molecules in Human Diseases.

The solute carrier family 4 (SLC4) is an important protein responsible for the transport of various ions across the cell membrane and mediating diverse physiological functions, such as the ion transporting function, protein-to-protein interactions, and molecular transduction. The deficiencies in SLC4 molecules may cause multisystem disease involving, particularly, the respiratory system, digestive, urinary, endocrine, hematopoietic, and central nervous systems. Currently, there are no effective strategies to treat these diseases. SLC4 proteins are also found to contribute to tumorigenesis and development, and some of them are regarded as therapeutic targets in quite a few clinical trials. This indicates that SLC4 proteins have potential clinical prospects. In view of their functional characteristics, there is a critical need to review the specific functions of bicarbonate transporters, their related diseases, and the involved pathological mechanisms. We summarize the diseases caused by the mutations in SLC4 family genes and briefly introduce the clinical manifestations of these diseases as well as the current treatment strategies. Additionally, we illustrate their roles in terms of the physiology and pathogenesis that has been currently researched, which might be the future therapeutic and diagnostic targets of diseases and a new direction for drug research and development.

A nomogram based on the risk factors of cervical lymph node metastasis in papillary thyroid carcinoma coexistent with Hashimoto's thyroiditis.

OBJECTIVE: The purpose of this study was to explore the risk factors of cervical lymph node metastasis(LNM) in papillary thyroid carcinoma(PTC) coexistent with Hashimoto's thyroiditis(HT). METHODS: The clinical data of patients who underwent thyroid operation between November 2016 and January 2020 in our hospital were analyzed retrospectively. The association between sonographic features and the risk factors of cervical LNM in PTC coexistent with HT was analyzed and a nomogram based on the risk factors was built. RESULTS: Age, US features as calcification, blood flow type, distance between thyroid nodule and fibrous capsule were risk factors of cervical LNM(P < 0.05).Size, SWVmax and SWVmean of thyroid nodule, SWVratio between thyroid nodule and thyroid gland were higher in PTCs with LNM than those without LNM(P < 0.05). The ROC curve showed that the cutoff value of SWVratio for predicting LNM was 1.29 (Sensitivity = 0.806, Specificity = 0.775, AUC = 0.823, P < 0.001). Based on the risk factors above, a relevant nomogram prediction model was established. The model verification showed that the C-index of the modeling set was 0.814, indicating that the nomogram model had good predicted accuracy. CONCLUSION: Based on the risk factors above, a relevant nomogram prediction model was established. The model verification showed that the C-index of the modeling set was 0.814, indicating that the nomogram model had good predicted accuracy. The nomogram based on the risk factors above had good prediction ability, which could optimize thyroidectomy and cervical lymph node dissection and improving prognosis.

[Research progress on structure, function and disease correlation of solute carrier family 4].

The solute carrier family 4 (SLC4) includes 10 members (SLC4A1-5, SLC4A7-11), which are expressed in multiple tissues in the human body. The SLC4 family members differ in their substrate dependence, charge transport stoichiometry and tissue expression. Their common function is responsible for the transmembrane exchange of multiple ions, which is involved in many important physiological processes, such as erythrocyte CO2 transport and the regulation of cell volume and intracellular pH. In recent years, many studies have focused on the role of SLC4 family members in the occurrence of human diseases. When SLC4 family members have gene mutations, a series of functional disorders will occur in the body, leading to the occurrence of some diseases. This review summarizes the recent progress about the structures, functions and disease correlation of SLC4 members, in order to provide clues for the prevention and treatment of related human diseases.

Genome-wide characterization of aldehyde dehydrogenase gene family members in groundnut (Arachis hypogaea) and the analysis under saline-alkali stress.

Groundnut or peanut (Arachis hypogaea) is a legume crop. Its seeds are rich in protein and oil. Aldehyde dehydrogenase (ALDH, EC: 1.2.1.3) is an important enzyme involved in detoxification of aldehyde and cellular reactive oxygen species, as well as in attenuation of lipid peroxidation-meditated cellular toxicity under stress conditions. However, few studies have been identified and analyzed about ALDH members in Arachis hypogaea. In the present study, 71 members of the ALDH superfamily (AhALDH) were identified using the reference genome obtained from the Phytozome database. A systematic analysis of the evolutionary relationship, motif, gene structure, cis-acting elements, collinearity, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and expression patterns was conducted to understand the structure and function of AhALDHs. AhALDHs exhibited tissue-specific expression, and quantitative real-time PCR identified significant differences in the expression levels of AhALDH members under saline-alkali stress. The results revealed that some AhALDHs members could be involved in response to abiotic stress. Our findings on AhALDHs provide insights for further study.

Molecular mechanisms of flavonoid accumulation in germinating common bean (Phaseolus vulgaris) under salt stress.

Flavonoids are important secondary metabolites, active biomolecules in germinating beans, and have prominent applications in food and medicine due to their antioxidant effects. Rutin is a plant flavonoid with a wide biological activity range. In this study, flavonoid (rutin) accumulation and its related molecular mechanisms in germinating common bean (Phaseolus vulgaris) were observed at different time points (0-120 h) under salt stress (NaCl). The rutin content increased from germination onset until 96 h, after which a reducing trend was observed. Metabolome analysis showed that salt stress alters flavonoid content by regulating phenylpropanoid (ko00940) and flavonoid (ko00941) biosynthesis pathways, as well as their enzyme activities, including cinnamyl-alcohol dehydrogenase (CAD), peroxidase (POD), chalcone isomerase (CHI), and flavonol synthase (FLS). The RNA-seq and quantitative real-time PCR (qRT-PCR) analyses also showed that these two pathways were linked to changes in flavonoid content following salt treatment. These results reveal that salt stress effectively enhanced rutin content accumulation in germinating beans, hence it could be employed to enhance the functional quality of germinating common beans.

RNA-Seq Analysis Demonstrates Different Strategies Employed by Tiger Nuts (Cyperus esculentus L.) in Response to Drought Stress.

Drought stress, an important abiotic stress, has affected global agricultural production by limiting the yield and the quality of crops. Tiger nuts (Cyperus esculentus L.) are C4 crops in the Cyperaceae family, which have high-quality wholesome ingredients. However, data on mechanisms underlying the response of tiger nuts to drought stress are few. Here, the variety of Jisha 1 and 15% polyethylene glycol (PEG; a drought stress simulator) were used to study the mechanisms of stress response in tiger nuts. Our evaluation of the changes in physiological indicators such as electrolyte leakage (El), malondialdehyde (MDA), hydrogen peroxide (H2O2), superoxide anion (O2-) and activities of reactive oxygen species (ROS) showed that 12 h was the most suitable time point to harvest and analyze the response to drought stress. Thereafter, we performed transcriptome (RNA-Seq) analysis in the control (CK) and stress treatment groups and showed that there was a total of 1760 differentially expressed genes (DEGs). Gene Ontology (GO) analysis showed that the DEGs were enriched in abscisic acid (ABA) terms, and pathways such as starch and sucrose metabolism (ko00500), phenylpropanoid biosynthesis (ko00940) and plant hormone signal transduction (ko04075) were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, quantitative real-time PCR (qRT-PCR) analysis of the DEGs demonstrated an upregulation of ABA and lignin content, as well as enzyme activities in enriched pathways, which validated the RNA-Seq data. These results revealed the pathways and mechanisms adopted by the tiger nuts in response to drought stress.

Different precompression does not reduce the diagnostic value of virtual touch tissue imaging and quantification (VTIQ) in breast lesions, especially for the ratio of the shear wave velocity between lesions and surrounding tissues.

OBJECTIVE: To investigate the accuracy of virtual touch tissue imaging and quantification (VTIQ) in the diagnosis of benign and malignant breast lesions under four different precompression levels. The shear wave velocity (SWV) ratios of lesion to surrounding tissue were also added for diagnosis. METHODS: 167 female patients with breast lesions were included in this single center prospective study. VTIQ was performed under four different precompression levels. The SWV of the lesion, surrounding fat, and gland tissue were measured at the same depth as much as feasible 7 times. The breast lesions studied were all histopathologically confirmed. The VTIQ parameters were compared between precompression levels. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnostic performance of each parameter of the VTIQ. RESULTS: The VTIQ parameters of the malignant lesions were significantly higher than those of benign lesions in all precompression levels (P < 0.001). SWV of the lesion, fat, and gland tissue increased significantly with increasing precompression. The VTIQ parameters had great diagnostic performance for breast lesions in all precompression levels (AUC = 0.765-0.911). There was no significant difference between the precompression levels of the lesion-to-fat SWV ratio and the lesion-to-gland SWV ratio in benign and malignant lesions, and the cut-off coefficients of variation were 7.42% and 8.55%, respectively. CONCLUSIONS: Precompression can increase the stiffness of breast lesions, fat and gland tissues, but does not reduce diagnostic value of VTIQ parameters in the breast. Under different precompression levels, the diagnosis of breast lesions by the ratio of the SWV of the lesion to the surrounding tissues is more stable.