Spatiotemporal variations of zooplankton community structure in the oyster (Crassostrea gigas)-macroalgae reef dual ecosystems adjacent to Luanhe River Estuary.

Majority of macrozooplankton have a wider dietary niche breadth and utilize small invertebrates, microzooplankton and mesozooplankton, so effect on primary production might be through trophic cascading effect. To better understand the ecosystem structure of benthic oyster-macroalgae reefs, we analyzed zooplankton community structure before (July 2016) and after (from September 2016 to October 2017) the construction of benthic reefs in the 2 km2 sea ranch area in Xiangyun Cove, Tangshan, China. We identified 57 zooplankton species, including the 12 cnidarian (e.g., Clytia hemisphaerica Linnaeus and Eirene ceylonensis Browne), 1 ctenopharyngodon (Pleurobrachia globosa Moser), 24 crustacean (e.g., Calanus sinicus Brodsky, Paracalanus parvus Claus, Labibocera euchaeta Glesbrecht, Labibocera bipinnata Tanaka, Calanopia thompsoni Scott, and Centropages dorsispinatus Thompson), 1 chaetognath (Sagitta crassa Tokioka), 1 urochordate species (Oikopleura dioica Fol), and 18 species of planktonic polychaete and gastropod larvae. The zooplankton density and biomass values before reef construction were 266.14 ind/m3 and 2.72 mg/m3, respectively, and those after reef construction were 138.06 ind/m3 and 32.91 mg/m3, respectively. The biomass trend was as follow: October 2017 (89.08 mg/m3) > August 2017 (70.97) > September 2016 (3.17) > July 2016 (2.72) > June 2017 (0.86) > May 2017 (0.44). The common dominant organisms were crustaceans and chaetognaths. According to the RDA ranking results, water temperature was positively correlated with the Shannon-Wiener diversity index and Margalef's richness indexes. With the increasement of Margalef's richness index, the value of dissolved oxygen content showed a significant negative correlation with zooplankton abundance. The results of this study are applicable to sustainable development and management strategies of coastal reef ecosystems and provide a basis for further surveys of secondary productivity in the sea ranch area.

Association of apolipoprotein A1 levels with lumbar bone mineral density and ß-CTX in osteoporotic fracture individuals: a cross-sectional investigation.

Background: The relationship between the levels of high-density lipoprotein (HDL) and bone mineral density (BMD) is controversial. Furthermore, the specific role of apolipoprotein A1 (APOA1), a primary HDL component, in regulating BMD remains unclear. This study aimed to elucidate the correlation between APOA1 levels and lumbar BMD in patients with osteoporotic fracture (OPF) for novel insights into potential therapeutic strategies against osteoporosis. Methods: This study included 587 OPF patients enrolled at the Kunshan Hospital, Affiliated with Jiangsu University between January 2017 and July 2022. The patient's serum APOA1 levels were determined, followed by the assessment of lumbar BMD and C-terminal telopeptide of type I collagen (ß-CTX) as outcome variables. The association of APOA1 levels with lumbar BMD and ß-CTX was assessed via Generalized Estimating Equations (GEE) and spline smoothing plot analyses. A generalized additive model (GAM) helped ascertain non-linear correlations. Moreover, a subgroup analysis was also conducted to validate the result's stability. Results: It was observed that APOA1 levels were positively correlated with lumbar BMD (ß = 0.07, 95% CI: 0.02 to 0.11, p = 0.0045), indicating that increased APOA1 levels were linked with enhanced lumbar BMD. Furthermore, APOA1 levels were negatively related to ß-CTX (ß = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003), suggesting APOA1 might reduce osteolysis. In addition, these findings were robustly supported by subgroup and threshold effect analyses. Conclusion: This study indicated that increased APOA1 levels were correlated with enhanced lumbar BMD and decreased osteolysis in OPF patients. Therefore, APOA1 may inhibit osteoclast activity to prevent further deterioration in osteoporotic patients. However, further research I warranted to validate these conclusions and elucidate the underlying physiologies.

Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an immune-related disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The complete pathogenesis of the virus remains to be determined. Unraveling the molecular mechanisms governing SARS-CoV-2 interactions with host cells is crucial for the formulation of effective prophylactic measures and the advancement of COVID-19 therapeutics. METHODS: We analyzed human lung single-cell RNA sequencing dataset to discern the association of butyrophilin subfamily 3 member A2 (BTN3A2) expression with COVID-19. The BTN3A2 gene edited cell lines and transgenic mice were infected by live SARS-CoV-2 in a biosafety level 3 (BSL-3) laboratory. Immunoprecipitation, flow cytometry, biolayer interferometry and competition ELISA assays were performed in BTN3A2 gene edited cells. We performed quantitative real-time PCR, histological and/or immunohistochemical analyses for tissue samples from mice with or without SARS-CoV-2 infection. FINDINGS: The BTN3A2 mRNA level was correlated with COVID-19 severity. BTN3A2 expression was predominantly identified in epithelial cells, elevated in pathological epithelial cells from COVID-19 patients and co-occurred with ACE2 expression in the same lung cell subtypes. BTN3A2 targeted the early stage of the viral life cycle by inhibiting SARS-CoV-2 attachment through interactions with the receptor-binding domain (RBD) of the Spike protein and ACE2. BTN3A2 inhibited ACE2-mediated SARS-CoV-2 infection by reducing ACE2 in vitro and in vivo. INTERPRETATION: These results reveal a key role of BTN3A2 in the fight against COVID-19. Identifying potential monoclonal antibodies which mimic BTN3A2 may facilitate disruption of SARS-CoV-2 infection, providing a therapeutic avenue for COVID-19. FUNDING: This study was supported by the National Natural Science Foundation of China (32070569, U1902215, and 32371017), the CAS "Light of West China" Program, and Yunnan Province (202305AH340006).

Machine learning risk prediction model for bloodstream infections related to totally implantable venous access ports in patients with cancer.

Objective: This study aimed to develop and validate a machine learning-based risk prediction model for catheter-related bloodstream infection (CRBSI) following implantation of totally implantable venous access ports (TIVAPs) in patients. Methods: A retrospective cohort study design was employed, utilizing the R software package mlr3. Various algorithms including logistic regression, naive Bayes, K nearest neighbor, classification tree, and random forest were applied. Addressing class imbalance, benchmarks were used, and model performance was assessed using the area under the curve (AUC). The final model, chosen for its superior performance, was interpreted using variable importance scores. Additionally, a nomogram was developed to calculate individualized risk probabilities, enhancing clinical utility. Results: The study involved 755 patients across both development and validation cohorts, with a TIVAP-CRBSI rate of 14.17%. The random forest model demonstrated the highest discrimination ability, achieving a validated AUC of 0.94, which was consistent in the validation cohort. Conclusions: This study successfully developed a robust predictive model for TIVAP-CRBSI risk post-implantation. Implementation of this model may aid healthcare providers in making informed decisions, thereby potentially improving patient outcomes.

Exosomes: Emerging Insights into the Progression of Pancreatic Cancer.

Pancreatic cancer is a very aggressive and fatal malignancy with few therapeutic choices and a poor prognosis. Understanding the molecular pathways that drive its growth is critical for developing effective therapeutic strategies. Exosomes, small extracellular vesicles secreted by numerous cell types, have recently emerged as essential intercellular communication mediators, with implications for tumor growth and metastasis. In this article, we present a review of current knowledge about exosomes and their role in pancreatic cancer progression We discuss the biogenesis and characteristics of exosomes, as well as their cargo and functional significance in tumor growth, immune evasion, angiogenesis, invasion, and metastasis. We further emphasize the potential of exosomes as diagnostic biomarkers and therapeutic targets for pancreatic cancer. Finally, we discuss the challenges and future perspectives in using exosomes to improve patient outcomes in pancreatic cancer.

Assessment and phenotypic identification of millet germplasm (Setaria italica L.) in Liaoning, China.

Aims: This study evaluated millet germplasms in Liaoning Province to support the collection, preservation and innovation of millet germplasm resources. Methods: The study was conducted from 2018 to 2020, involved the selection of 105 millet germplasm resources from the Germplasm Bank of the Liaoning Academy of Agricultural Sciences (LAAS), the observation and recording of 31 traits, and the application of multivariate analysis methods to assess phenotypic diversity. Results: From the diversity analysis and correlation analysis, it was found that the tested traits had abundant diversity and complex correlations among them. Principal component analysis (PCA) comprehensively analyzed all quantitative traits and extracted seven principal components. Grey relational analysis (GRA) highlighted the varied contributions of different traits to yield. Through systematic cluster analysis (SCA), the resources were categorized into six groups at Euclidean distance of 17.09. K-mean cluster analysis determined the distribution interval and central value of each trait, then identified resources with desirable traits. Conclusion: The results revealed resources that possess characteristics such as upthrow seedling leaves, more tillers and branches, larger and well-formed ears, and lodging resistance prefer to higher grain yield. It was also discovered that the subear internode length (SIL) could be an indicator for maturity selection. Four specific resources, namely, Dungu No. 1, Xiao-li-xiang, Basen Shengu, and Yuhuanggu No. 1, were identified for further breeding and practical applications.

Dynamic functional network connectivity in patients with a mismatch between white matter hyperintensity and cognitive function.

Objective: White matter hyperintensity (WMH) in patients with cerebral small vessel disease (CSVD) is strongly associated with cognitive impairment. However, the severity of WMH does not coincide fully with cognitive impairment. This study aims to explore the differences in the dynamic functional network connectivity (dFNC) of WMH with cognitively matched and mismatched patients, to better understand the underlying mechanisms from a quantitative perspective. Methods: The resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive function scale assessment of the patients were acquired. Preprocessing of the rs-fMRI data was performed, and this was followed by dFNC analysis to obtain the dFNC metrics. Compared the dFNC and dFNC metrics within different states between mismatch and match group, we analyzed the correlation between dFNC metrics and cognitive function. Finally, to analyze the reasons for the differences between the mismatch and match groups, the CSVD imaging features of each patient were quantified with the assistance of the uAI Discover system. Results: The 149 CSVD patients included 20 cases of "Type I mismatch," 51 cases of Type I match, 38 cases of "Type II mismatch," and 40 cases of "Type II match." Using dFNC analysis, we found that the fraction time (FT) and mean dwell time (MDT) of State 2 differed significantly between "Type I match" and "Type I mismatch"; the FT of States 1 and 4 differed significantly between "Type II match" and "Type II mismatch." Correlation analysis revealed that dFNC metrics in CSVD patients correlated with executive function and information processing speed among the various cognitive functions. Through quantitative analysis, we found that the number of perivascular spaces and bilateral medial temporal lobe atrophy (MTA) scores differed significantly between "Type I match" and "Type I mismatch," while the left MTA score differed between "Type II match" and "Type II mismatch." Conclusion: Different mechanisms were implicated in these two types of mismatch: Type I affected higher-order networks, and may be related to the number of perivascular spaces and brain atrophy, whereas Type II affected the primary networks, and may be related to brain atrophy and the years of education.

MS2/GmAMS1 encodes a bHLH transcription factor important for tapetum degeneration in soybean.

KEY MESSAGE: GmAMS1 is the only functional AMS and works with GmTDF1-1 and GmMS3 to orchestrate the tapetum degeneration in soybean. Heterosis could significantly increase the production of major crops as well as soybean [Glycine max (L.) Merr.]. Stable male-sterile/female-fertile mutants including ms2 are useful resources to apply in soybean hybrid production. Here, we identified the detailed mutated sites of two classic mutants ms2 (Eldorado) and ms2 (Ames) in MS2/GmAMS1 via the high-throughput sequencing method. Subsequently, we verified that GmAMS1, a bHLH transcription factor, is the only functional AMS member in soybean through the complementary experiment in Arabidopsis; and elucidated the dysfunction of its homolog GmAMS2 is caused by the premature stop codon in the gene's coding sequence. Further qRT-PCR analysis and protein-protein interaction assays indicated GmAMS1 is required for expressing downstream members in the putative DYT1-TDF1-AMS-MYB80/MYB103/MS188-MS1 cascade module, and might regulate the upstream members in a feedback mechanism. GmAMS1 could interact with GmTDF1-1 and GmMS3 via different region, which contributes to dissect the mechanism in the tapetum degeneration process. Additionally, as a core member in the conserved cascade module controlling the tapetum development and degeneration, AMS is conservatively present in all land plant lineages, implying that AMS-mediated signaling pathway has been established before land plants diverged, which provides further insight into the tapetal evolution.

[Genome-wide screening and bioinformatics analysis of Cannabis sativa LecRLK gene family].

Lectin receptor-like kinase(LecRLK) is a class of phytokinase with lectin conserved domain, which plays an important role in plant resistance to biological and abiotic stresses, as well as plant growth and development. Cannabis sativa is an important multi-purpose plant, widely used in food, textile, medicine, and other fields. Genome-wide screening and expression analysis of the LecRLK family of C. sativa were performed in this paper, so as to provide scientific reference for functional analysis of the LecRLK family of C. sativa. Based on BLAST and HMM methods, 93 LecRLKs were identified in the whole genome of C. sativa, including 69 G types, 23 L types, and one C types. Subsequently, a series of bioinformatics analyses were performed on the LecRLK family members, and the physicochemical properties of the protein of the LecRLK family members were initially revealed. The prediction of cis-acting elements of promoters in family members showed that family members were regulated by hormones and stress response. The expression analysis showed that some family members were highly expressed in the roots, which may participate in the process of stress resistance. Several members were highly expressed in female flowers and may be involved in female flower development. This study provides a theoretical basis for further study of LecRLK gene function. Meanwhile, the expression analysis screens candidate LecRLK members who may participate in the resistance of C. sativa, which provides a theoretical basis for the subsequent selection of C. sativa varieties against resistance.

PPM1G promotes autophagy and progression of pancreatic cancer via upregulating HMGB1.

Pancreatic cancer remains one of the most aggressive and lethal malignancies worldwide, with a dismal 5-year relative survival rates of only 12%. Therefore, it is urgent to discover the key molecular markers to improve the therapeutic outcomes in pancreatic cancer. Herein, we first demonstrated that PPM1G is upregulated in pancreatic cancer and that PPM1G depletion decreases pancreatic cancer cell growth in vitro and in vivo. High PPM1G expression was linked to short overall survival of pancreatic cancer patients, which was further validated in the TCGA database. Moreover, by detecting Beclin 1, LC3-II, and SQSTM1/p62 expressions and observing autolysosome under transmission electron microscope, we discovered that PPM1G is a novel positive regulator of macroautophagy/autophagy. Furthermore, by using immunoprecipitation-mass spectrometry (IP-MS) analysis and following systemic molecular biology experiment, we demonstrated PPM1G promotes the autophagy and proliferation of pancreatic cancer by directly upregulating HMGB1. Additionally, patients with both high PPM1G and high HMGB1 exhibited poorer prognosis in our cohort. This study preliminarily investigated the possibility of PPM1G as a potential therapeutic target and prognostic biomarker in pancreatic cancer patients.

Impact of omega-3 fatty acids on hypertriglyceridemia, lipidomics, and gut microbiome in patients with type 2 diabetes.

BACKGROUND: Fish oil (FO), a mixture of omega-3 fatty acids mainly comprising docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been recommended for patients with type 2 diabetes (T2D) and hypertriglyceridemia. However, its effects on lipidomic profiles and gut microbiota and the factors influencing triglyceride (TG) reduction remain unclear. METHODS: We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 309 Chinese patients with T2D with hypertriglyceridemia (ClinicalTrials.gov: NCT03120299). Participants were randomly assigned (1:1) to receive either 4 g FO or corn oil for 12 weeks. The primary outcome was changes in serum TGs and the lipidomic profile, and the secondary outcome included changes in the gut microbiome and other metabolic variables. FINDINGS: The FO group had significantly better TG reduction (mean [95% confidence interval (CI)]: -1.51 [-2.01, -1.01] mmol/L) compared to the corn oil group (-0.66 [-1.15, -0.16] mmol/L, p = 0.02). FO significantly altered the serum lipid profile by reducing low-unsaturated TG species and increasing those containing DHA or EPA. FO had minor effects on gut microbiota, while baseline microbial features predicted the TG response to FO better than phenotypic or lipidomic features, potentially mediated by specific lipid metabolites. A total of 9 lipid metabolites significantly mediated the link between 4 baseline microbial variables and the TG response to FO supplementation. CONCLUSIONS: Our findings demonstrate differential impacts of omega-3 fatty acids on lipidomic and microbial profiles in T2D and highlight the importance of baseline gut microbiota characteristics in predicting the TG-lowering efficacy of FO. FUNDING: This study was funded by the National Nature Science Foundation.

Physiologically-based pharmacokinetic/pharmacodynamic modeling of meropenem in critically ill patients.

This study aimed to develop a physiologically based pharmacokinetic/pharmacodynamic model (PBPK/PD) of meropenem for critically ill patients. A PBPK model of meropenem in healthy adults was established using PK-Sim software and subsequently extrapolated to critically ill patients based on anatomic and physiological parameters. The mean fold error (MFE) and geometric mean fold error (GMFE) methods were used to compare the differences between predicted and observed values of pharmacokinetic parameters Cmax, AUC0-∞, and CL to evaluate the accuracy of the PBPK model. The model was verified using meropenem plasma samples obtained from Intensive Care Unit (ICU) patients, which were determined by HPLC-MS/MS. After that, the PBPK model was combined with a PKPD model, which was developed based on f%T > MIC. Monte Carlo simulation was utilized to calculate the probability of target attainment (PTA) in patients. The developed PBPK model successfully predicted the meropenem disposition in critically ill patients, wherein the MFE average and GMFE of all predicted PK parameters were within the 1.25-fold error range. The therapeutic drug monitoring (TDM) of meropenem was conducted with 92 blood samples from 31 ICU patients, of which 71 (77.17%) blood samples were consistent with the simulated value. The TDM results showed that meropenem PBPK modeling is well simulated in critically ill patients. Monte Carlo simulations showed that extended infusion and frequent administration were necessary to achieve curative effect for critically ill patients, whereas excessive infusion time (> 4 h) was unnecessary. The PBPK/PD modeling incorporating literature and prospective study data can predict meropenem pharmacokinetics in critically ill patients correctly. Our study provides a reference for dose adjustment in critically ill patients.

Centimeter-Scale Assembly of Fractal Organic Crystals with Crisscross Structures for Flexible Photosynapses.

Fractal assembly technology enables scalable construction of organic crystal patterns for emerging nanoelectronics and optoelectronics. Here, a polymer-templating assembly strategy is presented for centimeter-scale patterned growth of fractal organic crystals (FOCs). These structures are formed by drop-coating perylene solution directly onto a gelatin-modified surface, resulting in the formation of crisscross fractal patterns. By adjusting the tilt angle of the template, the morphology of FOCs can be effectively controlled, with the diameter distribution of each level branch ranging from hundreds to ten micrometers. The planar FOC device exhibits flexible photoreception and photosynaptic capabilities, with a high specific detectivity of 1.35 × 109 Jones and paired-pulse facilitation (PPF) index of 104%, withstanding a 0.5 cm bending radius during bending test. These findings present a reliable route for large-scale assembly of flexible organic crystalline materials toward neuromorphic electronics.

Unsupervised Part Discovery via Dual Representation Alignment.

Object parts serve as crucial intermediate representations in various downstream tasks, but part-level representation learning still has not received as much attention as other vision tasks. Previous research has established that Vision Transformer can learn instance-level attention without labels, extracting high-quality instance-level representations for boosting downstream tasks. In this paper, we achieve unsupervised part-specific attention learning using a novel paradigm and further employ the part representations to improve part discovery performance. Specifically, paired images are generated from the same image with different geometric transformations, and multiple part representations are extracted from these paired images using a novel module, named PartFormer. These part representations from the paired images are then exchanged to improve geometric transformation invariance. Subsequently, the part representations are aligned with the feature map extracted by a feature map encoder, achieving high similarity with the pixel representations of the corresponding part regions and low similarity in irrelevant regions. Finally, the geometric and semantic constraints are applied to the part representations through the intermediate results in alignment for part-specific attention learning, encouraging the PartFormer to focus locally and the part representations to explicitly include the information of the corresponding parts. Moreover, the aligned part representations can further serve as a series of reliable detectors in the testing phase, predicting pixel masks for part discovery. Extensive experiments are carried out on four widely used datasets, and our results demonstrate that the proposed method achieves competitive performance and robustness due to its part-specific attention. The code will be released upon paper acceptance.

Homeostatic Shrinkage of Dendritic Spines Requires Melatonin Type 3 Receptor Activation During Sleep.

High-frequency oscillatory activity in cognition-related neural circuits during wakefulness consistently induces the growth of dendritic spines and axonal terminals. Although these structural changes are essential for cognitive functions, it is hypothesized that if these newly expanded structures fail to establish functional connections, they may become superfluous. Sleep is believed to facilitate the reduction of such redundant structures to maintain neural homeostasis. However, the mechanisms underlying this pruning process during sleep remain poorly understood. In this study, that melatonin type 3 receptors (MT3Rs) are selectively expressed in the stellate neurons of the medial entorhinal cortex (MEC) is demonstrated, an area where high melatonin levels are detected during sleep. Activation of MT3Rs during sleep initiates the shrinkage of dendritic spines in stellate neurons by downregulating neural network activity and dephosphorylating synaptic proteins in the MEC. This process is disrupted when MT3R expression is knocked down or when MT3Rs are blocked during sleep. Notably, interference with MT3Rs in the MEC during sleep impairs the acquisition of spatial memory but does not affect object memory acquisition following sleep. These findings reveal novel molecular mechanisms involving melatonin and MT3Rs in the regulation of dendritic spine shrinkage during sleep, which is crucial for the acquisition and consolidation of spatial memory.

Fluorescent Polylactic acid composite incorporating lignin-based carbon quantum dots for sustainable 4D printing applications.

Fluorescent 4D printing materials, as innovative materials that combine fluorescent characteristics with 4D printing technology, have attracted widespread interest and research. In this study, green lignin-derived carbon quantum dots (CQDs) were used as the fluorescent module, and renewable poly(propylene carbonate) polyurethane (PPCU) was used for toughening. A new low-cost fluorescent polylactic acid (PLA) composite filament for 4D printing was developed using a simple melt extrusion method. The strength of the prepared composite was maintained at 32 MPa, while the elongation at break increased 8-fold (34 % increase), demonstrating excellent shape fixed ratio (∼99 %), recovery ratio (∼92 %), and rapid shape memory recovery speed. The presence of PPCU prevented fluorescence quenching of the CQDs in the PLA matrix, allowing the composite to emit bright green fluorescence under 365 nm ultraviolet light. The composite exhibited shear thinning behavior and had an ideal melt viscosity for 3D printing. The results obtained demonstrated the versatility of these easy-to-manufacture and low-cost filaments, opening up a novel and convenient method for the preparation of strong, tough, and multifunctional PLA materials, increasing their potential application value.

Construction of a redox-active metal-organic framework with an octanuclear lithium one-dimensional building block.

A stable lithium metal-organic framework, constructed using a redox-active N,N,N',N'-tetrakis(4-carboxyphenyl)-1,4-phenylenediamine linker and Li8 cluster-based one-dimensional rod secondary building unit, exhibits good stability and reversible redox activity. The Li8-MOF, which can be oxidized by AgNO3, has the potential to function as an electrochromic device, thereby advancing the development of smart MOF materials.

Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings from the 4C Study.

CONTEXT: Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies. OBJECTIVE: To investigate associations and genetic susceptibility between serum MCFAs and diabetes risk. METHODS: We investigated baseline serum MCFAs (n=5) in a nested case-control study comprising incident diabetes cases (n=1,707) and matched normoglycemic control subjects (n=1,707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants. RESULTS: In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% confidence intervals) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = 0.042, 0.034, and 0.037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = 0.003). CONCLUSIONS: These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk.

Curcumin inhibits the proliferation and migration of osteosarcoma by regulating the expression of super-enhancer-associated genes. / å§œé»„ç´ é€šè¿‡è°ƒæŽ§è¶ çº§å¢žå¼ºå­ç›¸å ³åŸºå› æŠ‘åˆ¶éª¨è‚‰ç˜¤çš„å¢žæ®–å’Œè¿ç§».

OBJECTIVES: Super-enhancer-associated genes may be closely related to the progression of osteosarcoma, curcumin exhibits a certain inhibitory effect on tumors such as osteosarcoma. This study aims to investigate the effects of curcumin on osteosarcoma in vitro and in vivo, and to determine whether curcumin can inhibit the progression of osteosarcoma by suppressing the expression of super-enhancer-associated genes LIM and senescent cell antigen-like-containing domain 1 (LIMS1), secreted protein acidic and rich in cysteine (SPARC), and sterile alpha motif domain containing 4A (SAMD4A). METHODS: Human osteosarcoma cell lines (MG63 cells or U2OS cells) were treated with 5 to 50 µmol/L curcumin for 24, 48, and 72 hours, followed by the methyl thiazolyl tetrazolium (MTT) assay to detect cell viability. Cells were incubated with dimethyl sulfoxide (DMSO) or curcumin (2.5, 5.0 µmol/L) for 7 days, and a colony formation assay was used to measure in vitro cell proliferation. After treatment with DMSO or curcumin (10, 15 µmol/L), a scratch healing assay and a transwell migration assay were performed to evaluate cell migration ability. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) and Western blotting were used to detect mRNA and protein expression levels of LIMS1, SPARC, and SAMD4A in the cells. An osteosarcoma-bearing nude mouse model was established, and curcumin was administered via gavage for 14 days to assess the impact of curcumin on tumor volume and weight in vivo. Real-time RT-PCR was used to measure mRNA expression levels of LIMS1, SPARC, and SAMD4A in the cancer and adjacent tissues from 12 osteosarcoma patients. RESULTS: After treating cells with different concentrations of curcumin for 24, 48, and 72 hours, cell viability were all significantly decreased. Compared with the DMSO group, the colony formation rates in the 2.5 µmol/L and 5.0 µmol/L curcumin groups significantly declined (both P<0.01). The scratch healing assay showed that, compared with the DMSO group, the migration rates of cells in the 10 µmol/L and 15 µmol/L curcumin groups were significantly reduced. The exception was the 10 µmol/L curcumin group at 24 h, where the migration rate of U2OS cells did not show a statistically significant difference (P>0.05), while all other differences were statistically significant (P<0.01 or P<0.001). The transwell migration assay results showed that the number of migrating cells in the 10 µmol/L and 15 µmol/L curcumin groups was significantly lower than that in the DMSO group (both P<0.001). In the in vivo tumor-bearing mouse experiment, the curcumin group showed a reduction in tumor mass (P<0.01) and a significant reduction in tumor volume (P<0.001) compared with the control group. Compared with the DMSO group, the mRNA expression levels of LIMS1, SPARC, and SAMD4A in the 10 µmol/L and 15 µmol/L curcumin groups were significantly down-regulated (all P<0.05). Additionally, the protein expression level of LIMS1 in U2OS cells in the 10 µmol/L curcumin group was significantly lower than that in the DMSO group (P<0.05). Compared with adjacent tissues, the mRNA expression level of SPARC in osteosarcoma tissues was significantly increased (P<0.001), while the mRNA expression levels of LIMS1 and SAMD4A did not show statistically significant differences (both P>0.05). CONCLUSIONS: Curcumin inhibits the proliferation and migration of osteosarcoma both in vitro and in vivo, which may be associated with the inactivation of super-enhancer-associated gene LIMS1.