Pollinator shift ensures reproductive success in a camouflaged alpine plant.

BACKGROUND AND AIMS: There are intrinsic conflicts between signalling to mutualists and concealing (camouflaging) from antagonists. Like animals, plants also use camouflage as a defence against herbivores. However, this can potentially reduce their attractiveness to pollinators. METHODS: Using Fritillaria delavayi, an alpine camouflaged plant with inter-population floral colour divergence, we tested the influence of floral trait differences on reproduction. We conducted pollination experiments, measured floral morphological characteristics, estimated floral colours perceived by pollinators, analysed floral scent, and investigated the reproductive successes in five populations. KEY RESULTS: We found that the reproduction of F. delavayi depends on pollinators. Under natural conditions, a flower-camouflaged population had a 100% fruit set and similar seed set to three out of four yellow-flowered populations. Bumblebees are important pollinators in the visually conspicuous yellow-flowered populations, whereas flies are the only pollinator in the flower-camouflaged population, visiting flowers more frequently than bumblebees. The camouflaged flowers cannot be discriminated from the rock background as perceived by pollinators, but may be located by flies through olfactory cues. CONCLUSIONS: Collectively, our results demonstrate that the flower-camouflaged population has different reproductive traits from the visually conspicuous yellow-flowered ones. A pollinator shift from bumblebees to flies, combined with high visitation frequency, compensates the attractiveness disadvantage in camouflaged plants.

Intraspecific floral colour variation in three Pedicularis species.

Flower constancy describes the phenomenon that pollinators tend to successively visit flowers of a single species during foraging, reducing reproductive interference in natural communities. The extent of flower constancy is largely determined by the floral traits of co-flowering species. Both higher inter-specific and lower intraspecific differences of floral traits should contribute to a higher level of flower constancy. However, previous studies mainly focused on interspecific difference, and the intraspecific variation (consistency) of floral traits received much less attention. We hypothesise that selection may favour lower intraspecific floral trait variation in communities composed of multiple co-flowering congeners. We investigated the floral colour variation of three focal Pedicularis species that share pollinators in 19 communities composed of either single or multiple Pedicularis species. Colour was quantified using image-based colour analysis as perceived by pollinators. We found that most of the intrapopulation floral colour variation was below the colour discrimination threshold of bumblebees, implying strongly constrained by the visual selection by pollinators. Contrary to the hypothesis, there is no significant difference in intraspecific floral colour variation between different community contexts. It may be due to the relatively large interspecific floral colour differences of most co-flowering species. The influence of community context on intraspecific variation may be reflected in floral traits other than colours.

KLF5-mediated pyroptosis of airway epithelial cells leads to airway inflammation in asthmatic mice through the miR-182-5p/TLR4 axis.

Asthma is viewed as an airway disease and an inflammatory condition. This study aims to reveal the role of Kruppel-like factor 5 (KLF5)-mediated pyroptosis of airway epithelial cells in airway inflammation in asthma. The asthmatic mouse model was established. The mice were infected with the lentivirus containing sh-KLF5, antagomiR-182-5p, and pc-Toll-like receptor 4 (TLR4). Airway hyperresponsiveness was measured, and the cells in bronchoalveolar lavage fluid (BALF) were sorted and counted. The expression levels of interleukin (IL)-4/IL-13/IL-6/IL-18/IL-1ß/NOD-like receptor family pyrin domain containing 3 (NLRP3)/N-gasdermin D (GSDMD-N)/cleaved caspase-1 were detected. The pathological changes in lung tissue were observed. The enrichment of KLF5 in the miR-182-5p promoter region was measured. The binding relationship among KLF5, miR-182-5p, and TLR4 were analyzed. KLF5 was highly expressed in asthmatic mice. Silencing KLF5 improved airway resistance and lung dynamic compliance, reduced the cells in BALF and the expression of IL-4/IL-13/IL-6/NLRP3/GSDMD-N/cleaved caspase-1/IL-18/IL-1ß, and alleviated the pathological changes. Mechanistically, KLF5 bonded to the miR-182-5p promoter to inhibit miR-182-5p expression, and miR-182-5p inhibited TLR4. Silencing miR-182-5p or TLR4 overexpression reversed the improvement of silencing KLF5 on airway inflammation and pyroptosis in asthmatic mice. In conclusion, KLF5 inhibited miR-182-5p to promote TLR4 expression, thus aggravating pyroptosis and airway inflammation in asthmatic mice.

Motion intention recognition of the affected hand based on the sEMG and improved DenseNet network.

The key to sEMG (surface electromyography)-based control of robotic hands is the utilization of sEMG signals from the affected hand of amputees to infer their motion intentions. With the advancements in deep learning, researchers have successfully developed viable solutions for CNN (Convolutional Neural Network)-based gesture recognition. However, most studies have primarily concentrated on utilizing sEMG data from the hands of healthy subjects, often relying on high-dimensional feature vectors obtained from a substantial number of electrodes. This approach has yielded high-performing sEMG recognition systems but has failed to consider the considerable inconvenience that the abundance of electrodes poses to the daily lives and work of patients. In this paper, we focused on transradial amputees and used sEMG data from the Ninapro DB3 database as our dataset. Firstly, we introduce a STFT (Short-Time Fourier Transform)-based time-frequency feature fusion map for sEMG. This map includes both time-frequency features and the time-frequency localization of sEMG signals. Secondly, we propose an Improved DenseNet (Dense Convolutional Network) model for recognizing motion intentions in the affected hand of amputees based on their sEMG signals. Finally, addressing the issue of optimizing the number of electrodes carried by amputees, we introduce the PCMIRR (Pearson Correlation and Motion Intention Recognition Rate) algorithm. This algorithm optimizes the number of channels by considering the Pearson correlation between the sEMG channels of amputees and the recognition rate of motion intentions in the affected hand based on single-channel sEMG data. The experimental results reveal that the recognition accuracy, recall, and F1 score achieved by the Improved DenseNet model were 93.82%, 93.61%, and 93.65%, respectively. When the number of electrodes was optimized to 8, the recognition accuracy reached 94.50%. In summary, this paper ultimately attained precise recognition of motion intentions in amputees' affected hands while utilizing the minimum number of sEMG channels. This method offers a novel approach to sEMG-based control of bionic robotic hands.

The mechanism of action and experimental verification of Gan-song Yin on renal clear cell carcinoma based on network pharmacology and bioinformatics.

BACKGROUND: Gan-song Yin (GSY) is originated from the scripture "Gan-song Pills", a medical work of the Ningxia ethnic minorities, and its treatment of kidney diseases has good results. Its method of treating Renal clear cell carcinoma (KIRC) is still unknown, nevertheless. METHODS: Firstly, utilizing a network pharmacology strategy to screen GSY for active components and targets and looking up KIRC-related targets in GeneCards and GEO databases. Secondly, protein interaction networks were constructed and analyzed for GO and KEGG enrichment. Molecular docking was then performed and clinical and other correlations of the network pharmacology results were analyzed using bioinformatic analysis methods. Finally, we performed in vitro cellular experiments with 786-O cells and ACHN cells to validate the results of network pharmacology and bioinformatic analysis. RESULTS: With the help of network pharmacological analysis, six hub targets were eliminated. Bioinformatics study revealed that the hub targets has clinically significant clinical guiding importance. The results showed that GSY inhibited the proliferation of 786-O cells and ACHN cells, induced cell apoptosis, blocked cell cycle, and reduced cell colony formation ability. qRT-PCR results showed that GSY promoted the expression of ALB and CASP3 genes, and inhibited the expression of EGFR, JUN, MYC and VEGFA genes. Western blot results showed that GSY could promote the expression of ALB and CASP3 protein, and inhibit the expression of EGFR, JUN, MYC and VEGFA protein. CONCLUSIONS: Network pharmacology and bioinformatics analysis showed that GSY could act on multiple targets through a variety of components to achieve the effect of treating KIRC. In this study, we confirmed that GSY inhibits KIRC by regulating the expression of core targets through in vitro cellular experiments, thus providing a reference for subsequent related studies.

Amide proton transfer-weighted magnetic resonance imaging for application in renal fibrosis: A radiological-pathological based analysis.

BACKGROUND: Renal fibrosis (RF) being the most important pathological change in the progression of CKD, is currently assessed by the evaluation of a biopsy. This present study aimed to apply a novel functional MRI (fMRI) protocol named amide proton transfer weighting (APTw) to evaluate RF non-invasively. METHODS: Male Sprague-Dawley (SD) rats were initially subjected to bilateral kidney ischemia/reperfusion injury (IRI), unilateral ureteral obstruction (UUO) and Sham operation, respectively. All rats underwent APT mapping on the 7th and the 14th day after operation. Besides, 26 patients undergoing renal biopsy at the Nephrology Department of Shanghai Tongji Hospital between July 2022 and May 2023. Patients underwent APT and apparent diffusion coefficient (ADC) mappings within 1 week before biopsy. MRI results of both patients and rats were calculated by comparing with gold standard histology for fibrosis assessment. RESULTS: In animal models, the cortical APT (cAPT) and medullary APT (mAPT) values were positively correlated with the degree of renal fibrosis. Compared to the sham group, IRI group showed significantly increased cAPT and mAPT values on the 7th and 14th day after surgery, but no group differences were found in ADC values. Similar results were found in human patients. Cortical/medullary APT values were significantly increased in patients with moderate-to-severe fibrosis than patients with mild fibrosis. ROC curve analysis indicated that APT value displayed a better diagnostic value for RF. Furthermore, combination of cADC and cAPT improved fibrosis detection by imaging variables alone (p<0.1). CONCLUSION: APT values had better diagnostic capability at early stage of RF compared to ADC values, and the addition of APT imaging to conventional ADC will significantly improve the diagnostic performance for predicting kidney fibrosis.

Multifunctionality of angiosperm floral bracts: a review.

Floral bracts (bracteoles, cataphylls) are leaf-like organs that subtend flowers or inflorescences but are of non-floral origin; they occur in a wide diversity of species, representing multiple independent origins, and exhibit great variation in form and function. Although much attention has been paid to bracts over the past 150 years, our understanding of their adaptive significance remains remarkably incomplete. This is because most studies of bract function and evolution focus on only one or a few selective factors. It is widely recognised that bracts experience selection mediated by pollinators, particularly for enhancing pollinator attraction through strong visual, olfactory, or echo-acoustic contrast with the background and through signalling the presence of pollinator rewards, either honestly (providing rewards for pollinators), or deceptively (attraction without reward or even trapping pollinators). However, studies in recent decades have demonstrated that bract evolution is also affected by agents other than pollinators. Bracts can protect flowers, fruits, or seeds from herbivores by displaying warning signals, camouflaging conspicuous reproductive organs, or by providing physical barriers or toxic chemicals. Reviews of published studies show that bracts can also promote seed dispersal and ameliorate the effects of abiotic stressors, such as low temperature, strong ultraviolet radiation, heavy rain, drought, and/or mechanical abrasion, on reproductive organs or for the plants' pollinators. In addition, green bracts and greening of colourful bracts after pollination promote photosynthetic activity, providing substantial carbon (photosynthates) for fruit or seed development, especially late in a plant's life cycle or season, when leaves have started to senesce. A further layer of complexity derives from the fact that the agents of selection driving the evolution of bracts vary between species and even between different developmental stages within a species, and selection by one agent can be reinforced or opposed by other agents. In summary, our survey of the literature reveals that bracts are multifunctional and subject to multiple agents of selection. To understand fully the functional and evolutionary significance of bracts, it is necessary to consider multiple selection agents throughout the life of the plant, using integrative approaches to data collection and analysis.

The association between trouble sleeping and obesity among the U.S. elderly from NHANES 2011-2014: A moderated mediation model of depressive symptoms and cognitive function.

BACKGROUND: Studies have shown a close association between trouble sleeping and obesity in older adults. However, no studies have explored the underlying mechanism of this relationship. The present study was designed to evaluate the roles of depressive symptoms and cognitive function in the association between trouble sleeping and obesity in older American adults. METHODS: A cross-sectional study with 2575 participants (≥60 years old) in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 was used for analysis. Obesity, depressive symptoms, and cognitive function (including Established Consortium for Word Learning in Alzheimer's Disease (CERAD-WL) (immediate learning and recall and delayed recall), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST)) were objectively measured, and trouble sleeping was assessed using a self-reported questionnaire. The moderated mediation analysis was conducted by Hayes' PROCESS macro. RESULTS: Trouble sleeping was positively associated with obesity among older adults. Depressive symptoms partially and indirectly mediated this association, and DSST moderated the association between trouble sleeping and depressive symptoms. Trouble sleeping had a lower impact on depressive symptoms in older adults with higher cognitive function. LIMITATIONS: The cross-sectional design prevents making causal inferences, and part of self-reported information was not objective enough. CONCLUSION: Cognitive function moderated the mediation of depressive symptoms on the indirect, positive association between trouble sleeping and obesity; hence, incorporating methods to strengthen cognitive function and alleviate depressive symptoms may help weak the link between trouble sleeping and obesity among older adults.

Oligodendrocytes Play a Critical Role in White Matter Damage of Vascular Dementia.

With the deepening of population aging, the treatment of cognitive impairment and dementia is facing increasing challenges. Vascular dementia (VaD) is a cognitive dysfunction caused by brain blood flow damage and one of the most common causes of dementia after Alzheimer's disease. White matter damage in patients with chronic ischemic dementia often occurs before cognitive impairment, and its pathological changes include leukoaraiosis, myelin destruction and oligodendrocyte death. The pathophysiology of vascular dementia is complex, involving a variety of neuronal and vascular lesions. The current proposed mechanisms include calcium overload, oxidative stress, nitrative stress and inflammatory damage, which can lead to hypoxia-ischemia and demyelination. Oligodendrocytes are the only myelinating cells in the central nervous system and closely associated with VaD. In this review article, we intend to further discuss the role of oligodendrocytes in white matter and myelin injury in VaD and the development of anti-myelin injury target drugs.

Secular trends of asthma mortality in China and the United States from 1990 to 2019.

BACKGROUND: Asthma imposes a large healthcare burden in China and the United States (US). However, the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the countries. The aim of this study was to compare the mortality and risk factors between China and the US. METHODS: The deaths, and mortality rates of asthma in China and the US during 1990-2019 were obtained from the Global Burden of Disease Study 2019. The age-period-cohort model was used to estimate these mortality rates based on a log-linear scale with additive age, period, and cohort effects. The population attributable fractions of risk factors for asthma were estimated. RESULTS: In 1990-2019, the asthma mortality rate was higher in China than in the US. The crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to 2019. The decline in mortality was more obvious in China. Mortality gap between the two countries was narrowing. A sex difference in asthma mortality was observed with higher mortality in males in China and females in the US. The age effects showed that mortality increased with age in adults older than 20 years, particularly in the elderly. Downward trends were generally observed in the period and cohort rate ratios in both countries, with China experiencing a more obvious decrease. Smoking and high body mass index (BMI) were the leading risk factors for asthma mortality in China and the US, respectively. Mortality attributable to occupational asthmagens and smoking decreased the most in China and the US, respectively. CONCLUSIONS: In 1990-2019, the asthma mortality rate was higher in China than in the US; however, the mortality gap has narrowed. Mortality increased with age in adults. The improvements in asthma death risk with period and birth cohort were more obvious in China than in the US. Smoking, high BMI, and aging are major health problems associated with asthma control. The role of occupational asthmagens in asthma mortality underscores the importance of management and prevention of occupational asthma.

Associations Between Serum TNF-α, IL-6, hs-CRP and GLMD in Obese Children and Adolescents: A Cross-Sectional Study.

Purpose: To explore the relationships between serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) levels and glucolipid metabolism disorders (GLMD) in obese children and adolescents. Patients and Methods: In this cross-sectional study, 105 obese children and adolescents were selected for the detection of TNF-α, IL-6, hs-CRP, and glycolipid metabolism indicators. All participants were divided into elevated TNF-α group (≥8.1 pg/mL; n=49) and normal TNF-α group (<8.1 pg/mL; n=56), elevated IL-6 group (≥5.9 pg/mL; n=13) and normal IL-6 group (<5.9 pg/mL; n=92), elevated hs-CRP group (≥3.0 mg/L; n=44) and normal hs-CRP group (<3.0 mg/L; n=61), respectively. Results: Low-density lipoprotein cholesterol (LDL-C) in the elevated TNF-α group was higher than that in the normal TNF-α group (P=0.010). TNF-α was positively correlated with LDL-C (P=0.005). Fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) in the elevated IL-6 group were higher than those in the normal IL-6 group (all for P <0.05), while high-density lipoprotein cholesterol (HDL-C) in the elevated IL-6 group was lower than that in the normal IL-6 group (P<0.001). IL-6 was positively correlated with FINS, 2-hour postprandial insulin, HOMA-IR and triglyceride (all for P <0.01), while was negatively correlated with HDL-C (P=0.006). Moreover, hs-CRP was positively correlated with FINS and HOMA-IR (all for P <0.05). Conclusion: There may be correlations between serum TNF-α, IL-6, hs-CRP levels and GLMD in obese children and adolescents. Attention should be paid to monitoring serum inflammatory factors and preventing their elevation in obese children and adolescents, thus reducing the occurrence of GLMD.

Tri-ponderal mass index as a screening tool for obesity prediction in children aged 6-9 years.

Objective: This study aimed to evaluate the efficiency of tri-ponderal mass index (TMI) in determining obesity in Chinese children aged 6-9 years, using the criteria of percentage of body fat (PBF) and body mass index z-scores (BMI-Z). Methods: The cross-sectional study included 5365 children, aged 6-9 years, who participated in the project survey "Group prevention and treatment of obesity among students and school health promotion in Shanghai" from September 2007 to September 2009. Height, weight, waist circumference, body mass index (BMI), TMI, waist-to-height ratio (WHtR), and PBF were recorded. Statistical analyses including Kolmogorov-Smirnov test, chi-square test, receiver operating characteristics curve, and kappa chi-square test were performed. Results: TMI for both sexes was relatively constant with increasing age, and statistically significant differences were not observed at some ages (P > 0.05 at 6, 7, 8, and 9 years). WHtR showed subtle changes, while BMI and PBF increased significantly with age in boys and girls (P < 0.01). Using BMI-Z criteria as the measure of general obesity, the results indicated that TMI cutoff values for 6-9 years were 14.60 kg/m3 for boys and 14.84 kg/m3 for girls (P < 0.001). Analysis of the agreement between TMI and BMI-Z showed that the kappa statistic was 0.826 in boys and 0.709 in girls (P < 0.001). Conclusion: TMI, as a constant tool, holds great potential as an alternative screening method for identifying children aged 6-9 years who may be at risk of obesity at an early stage.

Historical development of karst evergreen broadleaved forests in East Asia has shaped the evolution of a hemiparasitic genus Brandisia (Orobanchaceae).

Brandisia is a shrubby genus of about eight species distributed basically in East Asian evergreen broadleaved forests (EBLFs), with distribution centers in the karst regions of Yunnan, Guizhou, and Guangxi in southwestern China. Based on the hemiparasitic and more or less liana habits of this genus, we hypothesized that its evolution and distribution were shaped by the development of EBLFs there. To test our hypothesis, the most comprehensive phylogenies of Brandisia hitherto were constructed based on plastome and nuclear loci (nrDNA, PHYA and PHYB); then divergence time and ancestral areas were inferred using the combined nuclear loci dataset. Phylogenetic analyses reconfirmed that Brandisia is a member of Orobanchaceae, with unstable placements caused by nuclear-plastid incongruences. Within Brandisia, three major clades were well supported, corresponding to the three subgenera based on morphology. Brandisia was inferred to have originated in the early Oligocene (32.69 Mya) in the Eastern Himalayas-SW China, followed by diversification in the early Miocene (19.45 Mya) in karst EBLFs. The differentiation dates of Brandisia were consistent with the origin of keystone species of EBLFs in this region (e.g., Fagaceae, Lauraceae, Theaceae, and Magnoliaceae) and the colonization of other characteristic groups (e.g., Gesneriaceae and Mahonia). These findings indicate that the distribution and evolution of Brandisia were facilitated by the rise of the karst EBLFs in East Asia. In addition, the woody and parasitic habits, and pollination characteristics of Brandisia may also be the important factors affecting its speciation and dispersal.

A New Efficient Multi-Object Detection and Size Calculation for Blended Tobacco Shreds Using an Improved YOLOv7 Network and LWC Algorithm.

Detection of the four tobacco shred varieties and the subsequent unbroken tobacco shred rate are the primary tasks in cigarette inspection lines. It is especially critical to identify both single and overlapped tobacco shreds at one time, that is, fast blended tobacco shred detection based on multiple targets. However, it is difficult to classify tiny single tobacco shreds with complex morphological characteristics, not to mention classifying tobacco shreds with 24 types of overlap, posing significant difficulties for machine vision-based blended tobacco shred multi-object detection and unbroken tobacco shred rate calculation tasks. This study focuses on the two challenges of identifying blended tobacco shreds and calculating the unbroken tobacco shred rate. In this paper, a new multi-object detection model is developed for blended tobacco shred images based on an improved YOLOv7-tiny model. YOLOv7-tiny is used as the multi-object detection network's mainframe. A lightweight Resnet19 is used as the model backbone. The original SPPCSPC and coupled detection head are replaced with a new spatial pyramid SPPFCSPC and a decoupled joint detection head, respectively. An algorithm for two-dimensional size calculation of blended tobacco shreds (LWC) is also proposed, which is applied to blended tobacco shred object detection images to obtain independent tobacco shred objects and calculate the unbroken tobacco shred rate. The experimental results showed that the final detection precision, mAP@.5, mAP@.5:.95, and testing time were 0.883, 0.932, 0.795, and 4.12 ms, respectively. The average length and width detection accuracy of the blended tobacco shred samples were -1.7% and 13.2%, respectively. The model achieved high multi-object detection accuracy and 2D size calculation accuracy, which also conformed to the manual inspection process in the field. This study provides a new efficient implementation method for multi-object detection and size calculation of blended tobacco shreds in cigarette quality inspection lines and a new approach for other similar blended image multi-object detection tasks.

Hip circumference has independent association with the risk of hyperuricemia in middle-aged but not in older male patients with type 2 diabetes mellitus.

BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) are risk factors for hyperuricemia. However, which anthropometric indices can better predict incident hyperuricemia in patients with T2DM remains inconsistent. This study aimed to examine the associations between hyperuricemia and different anthropometric indices in middle-aged and older male patients with T2DM. METHODS: In this retrospective study, a total of 1447 middle-aged (45-65 years, n = 791) and older (≥ 65 years, n = 656) male patients with T2DM were collected from December 2015 to January 2020 at Shanghai Xinhua Hospital. Hyperuricemia was defined as a serum uric acid level above 7.0 mg/dL. Weight, height, waist circumference (WC) and hip circumference (HC) were measured by trained nurses at visit. RESULTS: The median uric acid level of subjects was 5.6 (interquartile ranges: 4.7-6.7) mg/dl, and 279 (19.3%) were hyperuricemia, with 146 (18.5%) in the middle-aged group, and 133 (20.3%) in the older group. After adjusting for age, duration of T2DM, fasting plasma glucose and insulin, homeostasis model assessment-ß, aspartate aminotransferase, triglycerides, high-density lipoprotein cholesterol and estimated glomerular filtration rate, body mass index (BMI), WC, HC, and waist-to-height ratio (WHtR) were associated with a higher risk of hyperuricemia in both middle-aged and older group (P < 0.05). After further adjusting for BMI and WC, HC still showed a positive relationship with the risk of hyperuricemia (Odds Ratio = 1.51, 95% confidence intervals: 1.06-2.14) in the middle-aged group, but such relationship was not found in the older group. Moreover, according to receiver operating characteristic analysis, the optimal cutoff value was 101.3 cm of HC for hyperuricemia screening in the middle-aged male patients with T2DM. CONCLUSION: In middle-aged male patients with T2DM, more attention should be paid to HC with the cutoff value of 101.3 cm in clinical practice for early recognition of individuals with a high risk of hyperuricemia for targeted guidance on disease prevention, such as community screening.

18ß-glycyrrhetinic acid inhibits proliferation of gastric cancer cells through regulating the miR-345-5p/TGM2 signaling pathway.

BACKGROUND: Gastric cancer (GC) is a common gastrointestinal malignancy worldwide. Based on cancer-related mortality, the current prevention and treatment strategies for GC still show poor clinical results. Therefore, it is important to find effective drug treatment targets. AIM: To explore the molecular mechanism of 18ß-glycyrrhetinic acid (18ß-GRA) regulating the miR-345-5p/TGM2 signaling pathway to inhibit the proliferation of GC cells. METHODS: CCK-8 assay was used to determine the effect of 18ß-GRA on the survival rate of GES-1 cells and AGS and HGC-27 cells. Cell cycle and apoptosis were detected by flow cytometry, cell migration was detected by a wound healing assay, the effect of 18ß-GRA on subcutaneous tumor growth in BALB/c nude mice was investigated, and the cell autophagy level was determined by MDC staining. TMT proteomic analysis was used to detect the differentially expressed autophagy-related proteins in GC cells after 18ß-GRA intervention, and then the protein-protein interaction was predicted using STRING (https://string-db.org/). MicroRNAs (miRNAs) transcriptome analysis was used to detect the miRNA differential expression profile, and use miRBase (https://www.mirbase/) and TargetScan (https://www.targetscan.org/) to predict the miRNA and complementary binding sites. Quantitative real-time polymerase chain reaction was used to detect the expression level of miRNA in 18ß-GRA treated cells, and western blot was used to detect the expression of autophagy related proteins. Finally, the effect of miR-345-5p on GC cells was verified by mir-345-5p overexpression. RESULTS: 18ß-GRA could inhibit GC cells viability, promote cell apoptosis, block cell cycle, reduce cell wound healing ability, and inhibit the GC cells growth in vivo. MDC staining results showed that 18ß-GRA could promote autophagy in GC cells. By TMT proteomic analysis and miRNAs transcriptome analysis, it was concluded that 18ß-GRA could down-regulate TGM2 expression and up-regulate miR-345-5p expression in GC cells. Subsequently, we verified that TGM2 is the target of miR-345-5p, and that overexpression of miR-345-5p significantly inhibited the protein expression level of TGM2. Western blot showed that the expression of autophagy-related proteins of TGM2 and p62 was significantly reduced, and LC3II, ULK1 and AMPK expression was significantly increased in GC cells treated with 18ß-GRA. Overexpression of miR-345-5p not only inhibited the expression of TGM2, but also inhibited the proliferation of GC cells by promoting cell apoptosis and arresting cell cycle. CONCLUSION: 18ß-GRA inhibits the proliferation of GC cells and promotes autophagy by regulating the miR-345-5p/TGM2 signaling pathway.

The Association Between Health-Related Behaviors and Traditional Chinese Medicine Syndromes in Type 2 Diabetes Mellitus Patients.

Background: Traditional Chinese medicine (TCM) has certain advantages in treating diabetes via TCM syndromes differentiation, and health-related behaviors can regulate TCM syndromes. This study aimed to identify the clusters of TCM syndromes in type 2 diabetes mellitus (T2DM) patients and to explore the association between health-related behaviors and those TCM syndromes clusters. Methods: This was a cross-sectional study of 1761 T2DM patients from the Ningxia Province. The TCM syndromes (11 TCM syndromes in total) scale was used to collect the syndrome information. Health-related behaviors, including smoking, alcohol use, tea drinking, the intensity of physical activity, sleep quality, and sleep duration, were collected via a face-to-face interview questionnaire. Latent profile analysis was employed to identify clusters of 11 TCM syndromes. Multinomial logistic regression was employed to examine the relationships between health-related behaviors and clusters of TCM syndromes. Results: TCM syndromes in T2DM patients were classified into three profiles using latent profile analysis: light, moderate, and heavy. Participants with poor health-related behaviors were more likely to have heavy 1.49 (95% CI: 1.12, 1.99) or moderate 1.75 (95% CI: 1.10, 2.79) profiles than those with good health-related habits. Smokers, tea drinkers, and those with poor sleep quality were more likely to have a moderate profile and heavy profile than a light profile. Compared with heavy physical activity, moderate activity 0.24 (95% CI: 0.07, 0.88) was negatively associated with a heavy profile. Conclusion: Results showed that most participants had light or moderate levels of TCM syndromes, and those with poor health-related behaviors were more likely to have heavy or moderate profiles. In the context of precision medicine, these results have important implications for understanding the prevention and treatment of diabetes via changing lifestyles and behaviors to regulate TCM syndromes.

Camouflaged plants are shorter than non-camouflaged plants in the alpine zone.

Camouflage has been reported as a defensive strategy in plants, while our understanding of the evolution of such defensive coloration is still limited. In the present study, we tested the hypothesis that camouflaged plants are shorter than non-camouflaged ones in the same habitat. Based on a species list from the subnival zone from the Hengduan Mountains, SW China and the herbarium collection, we measured the plant heights of 2915 individuals from 621 species (either camouflaged or not), with elevation information as a reference. We show that camouflaged plants were significantly shorter than non-camouflaged ones, though the effects of phylogeny and elevation were considered. Interestingly, a negative correlation between plant height and elevation was found in non-camouflaged plants, but not in camouflaged ones. These results revealed the correlation between defensive coloration and plant height. Camouflage may have evolved from shorter ancestors because they may suffer stronger selection and provide a more efficient defence.

Expression of αA-crystallin (CRYAA) in vivo and in vitro models of age-related cataract and the effect of its silencing on HLEB3 cells.

AIM: To investigate the expression of αA-crystallin (CRYAA) in age-related cataract (ARC) models and its role in lens epithelial cells (LECs). METHODS: We used Flow cytometry to detect the apoptosis and cell cycle in HLEB3 cells and Real-time fluorescence quantitative polymerase chain reaction to detect the expression of CRYAA mRNA in HLEB3 and in rabbit lens. The expression of CRYAA in HLEB3 cells and rabbit lenses as well as the proteins related to apoptosis and autophagy in transfected cells were detected by western blotting. The lens structure in rabbits was investigated using hematoxylin-eosin staining. Protein thermostability assay was performed to detect the thermal stability of rabbit lens proteins. CCK- 8 assay was used to detect the viability of transfected cells, and the transfection was recorded by fluorescence photography. RESULTS: Hydrogen peroxide can promote apoptosis and arrest the cell cycle in HLEB3 cells, and naphthalene can cause cataract formation and damage the structure of the lens in rabbits. Both ARC models can reduce the expression of CRYAA. The expression of CRYAA silencing increased apoptosis and autophagy in HLEB3 cells.

COX17 restricts renal fibrosis development by maintaining mitochondrial copper homeostasis and restoring complex IV activity.

Renal fibrosis relies on multiple proteins and cofactors in its gradual development. Copper is a cofactor of many enzymes involved in renal microenvironment homeostasis. We previously reported that intracellular copper imbalance occurred during renal fibrosis development and was correlated with fibrosis intensity. In this study, we investigated the molecular mechanisms of how copper affected renal fibrosis development. Unilateral ureteral obstruction (UUO) mice were used for in vivo study; rat renal tubular epithelial cells (NRK-52E) treated with TGF-ß1 were adapted as an in vitro fibrotic model. We revealed that the accumulation of copper in mitochondria, rather than cytosol, was responsible for mitochondrial dysfunction, cell apoptosis and renal fibrosis in both in vivo and in vitro fibrotic models. Furthermore, we showed that mitochondrial copper overload directly disrupted the activity of respiratory chain complex IV (cytochrome c oxidase), but not complex I, II and III, which hampered respiratory chain and disrupted mitochondrial functions, eventually leading to fibrosis development. Meanwhile, we showed that COX17, the copper chaperone protein, was significantly upregulated in the mitochondria of fibrotic kidneys and NRK-52E cells. Knockdown of COX17 aggravated mitochondrial copper accumulation, inhibited complex IV activity, augmented mitochondrial dysfunction and led to cell apoptosis and renal fibrosis, whereas overexpression of COX17 could discharge copper from mitochondria and protect mitochondrial function, alleviating renal fibrosis. In conclusion, copper accumulation in mitochondria blocks complex IV activity and induces mitochondrial dysfunction. COX17 plays a pivotal role in maintaining mitochondrial copper homeostasis, restoring complex IV activity, and ameliorating renal fibrosis.