Ocean acidification alters microeukaryotic and bacterial food web interactions in a eutrophic subtropical mesocosm.

Ocean acidification (OA) is known to influence biological and ecological processes, mainly focusing on its impacts on single species, but little has been documented on how OA may alter plankton community interactions. Here, we conducted a mesocosm experiment with ambient (∼410 ppmv) and high (1000 ppmv) CO2 concentrations in a subtropical eutrophic region of the East China Sea and examined the community dynamics of microeukaryotes, bacterioplankton and microeukaryote-attached bacteria in the enclosed coastal seawater. The OA treatment with elevated CO2 affected taxa as the phytoplankton bloom stages progressed, with a 72.89% decrease in relative abundance of the protist Cercozoa on day 10 and a 322% increase in relative abundance of Stramenopile dominated by diatoms, accompanied by a 29.54% decrease in relative abundance of attached Alphaproteobacteria on day 28. Our study revealed that protozoans with different prey preferences had differing sensitivity to high CO2, and attached bacteria were more significantly affected by high CO2 compared to bacterioplankton. Our findings indicate that high CO2 changed the co-occurrence network complexity and stability of microeukaryotes more than those of bacteria. Furthermore, high CO2 was found to alter the proportions of potential interactions between phytoplankton and their predators, as well as microeukaryotes and their attached bacteria in the networks. The changes in the relative abundances and interactions of microeukaryotes between their predators in response to high CO2 revealed in our study suggest that high CO2 may have profound impacts on marine food webs.

A fully automatic MRI-guided decision support system for lumbar disc herniation using machine learning.

Background: Normalized decision support system for lumbar disc herniation (LDH) will improve reproducibility compared with subjective clinical diagnosis and treatment. Magnetic resonance imaging (MRI) plays an essential role in the evaluation of LDH. This study aimed to develop an MRI-based decision support system for LDH, which evaluates lumbar discs in a reproducible, consistent, and reliable manner. Methods: The research team proposed a system based on machine learning that was trained and tested by a large, manually labeled data set comprising 217 patients' MRI scans (3255 lumbar discs). The system analyzes the radiological features of identified discs to diagnose herniation and classifies discs by Pfirrmann grade and MSU classification. Based on the assessment, the system provides clinical advice. Results: Eventually, the accuracy of the diagnosis process reached 95.83%. An 83.5% agreement was observed between the system's prediction and the ground-truth in the Pfirrmann grade. In the case of MSU classification, 95.0% precision was achieved. With the assistance of this system, the accuracy, interpretation efficiency and interrater agreement among surgeons were improved substantially. Conclusion: This system showed considerable accuracy and efficiency, and therefore could serve as an objective reference for the diagnosis and treatment procedure in clinical practice.

Single-cell analysis of CD4+ tissue residency memory cells (TRMs) in adult atopic dermatitis: A new potential mechanism.

The pathophysiology of atopic dermatitis (AD) is complex. CD4+ T cells play an essential role in the development of lesions in AD. However, the underlying mechanism remains unclear. In the present study, we investigated the differentially expressed genes (DEGs) between adult AD lesioned and non-lesioned skin using two datasets from the Gene Expression Omnibus (GEO) database. 62 DEGs were shown to be related to cytokine response. Compared to non-lesioned skin, lesioned skin showed immune infiltration with increased numbers of activated natural killer (NK) cells and CD4+ T memory cells (p < 0.01). We then identified 13 hub genes with a strong association with CD4+ T cells using weighted correlation network analysis. Single-cell analysis of AD detected a novel CD4+ T subcluster, CD4+ tissue residency memory cells (TRMs), which were verified through immunohistochemistry (IHC) to be increased in the dermal area of AD. The significant relationship between CD4+ TRM and AD was assessed through further analyses. FOXO1 and SBNO2, two of the 13 hub genes, were characteristically expressed in the CD4+ TRM, but down-regulated in IFN-γ/TNF-α-induced HaCaT cells, as shown using quantitative polymerase chain reaction (qPCR). Moreover, SBNO2 expression was associated with increased Th1 infiltration in AD (p < 0.05). In addition, genes filtered using Mendelian randomization were positively correlated with CD4+ TRM and were highly expressed in IFN-γ/TNF-α-induced HaCaT cells, as determined using qPCR and western blotting. Collectively, our results revealed that the newly identified CD4+ TRM may be involved in the pathogenesis of adult AD.

Long-term prognostic value of big endothelin-1 and its combination with late gadolinium enhancement in patients with idiopathic restrictive cardiomyopathy.

BACKGROUND AND AIMS: Idiopathic restrictive cardiomyopathy (RCM) has a low incidence. This study aimed to determine the prognostic value of big endothelin-1 (ET-1) in idiopathic RCM. MATERIALS AND METHODS: We prospectively enrolled patients with idiopathic RCM from 2009 to 2017 and followed them up. The primary outcome was a composite of all-cause mortality and cardiac transplantation, and the secondary outcome was a composite of cardiac death and cardiac transplantation. RESULTS: Ninety-one patients were divided into the high big ET-1 (>0.85 pmol/L, n = 56) and low big ET-1 (≤0.85 pmol/L, n = 35) groups, and 87 of them completed the follow-up. Big ET-1 concentrations (hazard ratio: 1.756, 95 % confidence interval [CI]: 1.117-2.760) and late gadolinium enhancement (LGE) (hazard ratio: 3.851, 95 % CI: 1.238-11.981) were independent risk factors for the primary outcome. Big ET-1 concentrations (C-statistic estimation: 0.764, 95 % CI: 0.657-0.871) and the combination of LGE and big ET-1 concentrations (C-statistic estimation: 0.870, 95 % CI: 0.769-0.970) could accurately predict the 5-year transplant-free survival rate, and 0.85 pmol/L was a suitable cutoff for big ET-1. CONCLUSION: Big ET-1 and its combination with LGE may be useful to predict an adverse prognosis in patients with idiopathic RCM.

Crosstalk among proximal tubular cells, macrophages, and fibroblasts in acute kidney injury: single-cell profiling from the perspective of ferroptosis.

The link between ferroptosis, a form of cell death mediated by iron and acute kidney injury (AKI) is recently gaining widespread attention. However, the mechanism of the crosstalk between cells in the pathogenesis and progression of acute kidney injury remains unexplored. In our research, we performed a non-negative matrix decomposition (NMF) algorithm on acute kidney injury single-cell RNA sequencing data based specifically focusing in ferroptosis-associated genes. Through a combination with pseudo-time analysis, cell-cell interaction analysis and SCENIC analysis, we discovered that proximal tubular cells, macrophages, and fibroblasts all showed associations with ferroptosis in different pathways and at various time. This involvement influenced cellular functions, enhancing cellular communication and activating multiple transcription factors. In addition, analyzing bulk expression profiles and marker genes of newly defined ferroptosis subtypes of cells, we have identified crucial cell subtypes, including Egr1 + PTC-C1, Jun + PTC-C3, Cxcl2 + Mac-C1 and Egr1 + Fib-C1. All these subtypes which were found in AKI mice kidneys and played significantly distinct roles from those of normal mice. Moreover, we verified the differential expression of Egr1, Jun, and Cxcl2 in the IRI mouse model and acute kidney injury human samples. Finally, our research presented a novel analysis of the crosstalk of proximal tubular cells, macrophages and fibroblasts in acute kidney injury targeting ferroptosis, therefore, contributing to better understanding the acute kidney injury pathogenesis, self-repairment and acute kidney injury-chronic kidney disease (AKI-CKD) progression.

Biomechanical changes in the proximal femur before and after removal of femoral neck system.

BACKGROUND: As an innovative internal fixation system, FNS (femoral neck system) is increasingly being utilized by surgeons for the treatment of femoral neck fractures. At present, there have been numerous finite element analysis experiments studying the immediate stability of FNS and CSS in treating femoral neck fractures. However, there is scarce mechanical analysis available regarding the effects post internal fixation removal. This study aimed to investigate the alterations in mechanical parameters of the proximal femur before and after the removal of FNS (femoral neck system), and to assess potential distinctions in indicators following the extraction of CSS (Cannulated Screws). METHODS: A proximal femur model was reconstructed using finite element numerical techniques. The models for CSS and FNS were formulated utilizing characteristics and parametric definitions. The internal fixation was combined with a normal proximal femur model to simulate the healing state after fracture surgery. Within the framework of static analysis, consistent stress burdens were applied across the entirety of the models. The total deformation and equivalent stress of the proximal femur were recorded before and after the removal of internal fixation. RESULTS: Under the standing condition, the total deformation of the model before and after removing CSS was 0.99 mm and 1.10 mm, respectively, indicating an increase of 12%. The total deformation of the model before and after removing FNS was 0.65 mm and 0.76 mm, respectively, indicating an increase of 17%. The equivalent stress for CSS and FNS were 55.21 MPa and 250.67 MPa, respectively. The average equivalent stress on the cross-section of the femoral neck before and after removal of CSS was 7.76 MPa and 6.11 MPa, respectively. The average equivalent stress on the cross-section of the femoral neck before and after removal of FNS was 9.89 MPa and 8.79 MPa, respectively. CONCLUSIONS: The retention of internal fixation may contribute to improved stability of the proximal femur. However, there still existed risks of stress concentration in internal fixation and stress shielding in the proximal femur. Compared to CSS, the removal of FNS results in larger bone tunnels and insufficient model stability. Further clinical interventions are recommended to address this issue.

Effect of continuous measurement and adjustment of endotracheal tube cuff pressure on postoperative sore throat in patients undergoing gynecological laparoscopic surgery: a randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a common complication following endotracheal tube removal, and effective preventive strategies remain elusive. This trial aimed to determine whether actively regulating intraoperative cuff pressure below the tracheal capillary perfusion pressure threshold could effectively reduce POST incidence in patients undergoing gynecological laparoscopic procedures. METHODS: This single-center, randomized controlled superiority trial allocated 60 patients scheduled for elective gynecological laparoscopic procedures into two groups: one designated for cuff pressure measurement and adjustment (CPMA) group, and a control group where only cuff pressure measurement was conducted without any subsequent adjustments. The primary outcome was POST incidence at rest within 24 h post-extubation. Secondary outcomes included cough, hoarseness, postoperative nausea and vomiting (PONV) incidence, and post-extubation pain severity. RESULTS: The incidence of sore throat at rest within 24 h after extubation in the CPMA group was lower than in the control group, meeting the criteria for statistically significant superiority based on a one-sided test (3.3% vs. 26.7%, P < 0.025). No statistically significant differences were observed in cough, hoarseness, or pain scores within 24 h post-extubation between the two groups. However, the CPMA group had a higher incidence of PONV compared to the control group. Additionally, the control group reported higher sore throat severity scores within 24 h post-extubation. CONCLUSIONS: Continuous monitoring and maintenance of tracheal tube cuff pressure at 18 mmHg were superior to merely monitoring without adjustment, effectively reducing the incidence of POST during quiet within 24 h after tracheal tube removal in gynecological laparoscopic surgery patients. TRIAL REGISTRATION: The study was registered at www.chictr.org.cn (ChiCTR2200064792) on 18/10/2022.

Enabling Ultrastable Co-Free Li-Rich Oxides via TbF3 Treatment.

Co-free Li-rich Mn-based cathode materials (Co-free LRMOs) have become one of the most promising cathode materials in lithium-ion batteries for the next generation due to their low cost, high capacity, and environmental friendliness. Under high voltage, redox reactions involving anions can easily lead to various issues, including oxygen release, dissolution of transition metal elements (TMs), and structural collapse in these materials. The absence of the Co element further exacerbates this issue. Here, a simple one-step solid-phase reaction strategy is proposed to achieve nanoscale dual modification of the Co-free LRMOs with F and Tb doping. The dual modification has a relatively small impact on the cell parameters and Li+ diffusion ability of the LRMOs, leading to no significant improvement in its rate performance. The modified LRMOs only exhibited discharge capacities of 220.7, 200.1, 140.0, 115.5, and 90.9 mAh·g-1 at 0.1, 0.2, 1.0, 2.0, and 5.0 C, respectively. However, the modified Co-free LRMOs exhibit extremely strong structural stability and retain 95.1% of the initial capacity after 300 cycles, so far, the highest capacity retention rates among all Ni/Mn-based Li-rich materials. Mechanism studies have shown that the enhancement in structural stability of the Co-free LRMOs is attributed to the increased concentration of oxygen vacancies and Ni3+ ions through F doping. Furthermore, Tb doping not only hinders the release of O2 but also enhances the Li+ migration and electronic conductivity coefficient of the LRMOs.

A novel quantitative method to evaluate lumbar disc degeneration: MRI histogram analysis.

PURPOSE: This study aimed to use MRI histogram analysis to routine MRI sequences to evaluate lumbar disc degeneration (LDD), illustrate the correlation between this novel method and the traditional Pfirrmann classification method, and more importantly, perform comprehensive agreement analysis of MRI histogram analysis in various situations to evaluate its objectivity and stability. METHODS: Lumbar MRI images from 133 subjects were included in this study. LDD was classified into grades by Pfirrmann classification and was measured as peak separation value by MRI histogram analysis. Correlation analysis between the two methods was performed and cutoff values were determined. In addition, the agreement analysis of peak separation value was performed by intraclass correlation coefficient (ICC) in four scenarios, including inter-resolution, inter-observer, inter-regions of interest (ROI) and inter-slice. RESULTS: Peak separation values were strongly correlated with Pfirrmann grades (r = - 0.847). The inter-resolution agreements of peak separation value between original image resolution of 2304 × 2304 and compressed image resolutions (1152 × 1152, 576 × 576, 288 × 288) were good to excellent (ICCs were 0.916, 0.876 and 0.822), except 144 × 144 was moderate (ICC = 533). The agreements of inter-observer (ICC = 0.982) and inter-ROI (ICC = 0.915) were excellent. Compared with the mid-sagittal slice, the inter-slice agreements were good for the first adjacent slices (ICCs were 0.826 and 0.844), and moderate to good for the second adjacent slices (ICC = 0.733 and 0.753). CONCLUSION: MRI histogram analysis, used in routine MRI sequences, demonstrated a strong correlation with Pfirrmann classification and good agreements in various scenarios, expanding the range of application and providing an effective, objective and quantitative tool to evaluate LDD.

Targeting programmed cell death in inflammatory bowel disease through natural products: New insights from molecular mechanisms to targeted therapies.

Inflammatory bowel disease (IBD) is an autoimmune disorder primarily characterized by intestinal inflammation and recurrent ulceration, leading to a compromised intestinal barrier and inflammatory infiltration. This disorder's pathogenesis is mainly attributed to extensive damage or death of intestinal epithelial cells, along with abnormal activation or impaired death regulation of immune cells and the release of various inflammatory factors, which contribute to the inflammatory environment in the intestines. Thus, maintaining intestinal homeostasis hinges on balancing the survival and functionality of various cell types. Programmed cell death (PCD) pathways, including apoptosis, pyroptosis, autophagy, ferroptosis, necroptosis, and neutrophil extracellular traps, are integral in the pathogenesis of IBD by mediating the death of intestinal epithelial and immune cells. Natural products derived from plants, fruits, and vegetables have shown potential in regulating PCD, offering preventive and therapeutic avenues for IBD. This article reviews the role of natural products in IBD treatment by focusing on targeting PCD pathways, opening new avenues for clinical IBD management.

NIR Absorbing Organic Chromophores Combination with NSAIDs for Remodeling of the Inflammatory Microenvironment to Amplify Tumor Ferroptosis-Photothermal Synergistic Therapy.

Photothermal therapy has emerged as a promising approach for cancer treatment, which can cause ferroptosis to enhance immunotherapeutic efficacy. However, excessively generated immunogenicity will induce serious inflammatory response syndrome, resulting in a discounted therapeutic effect. Herein, a kind of NIR absorption small organic chromophore nanoparticles (TTHM NPs) with high photothermal conversion efficiency (68.33%) is developed, which can induce mitochondria dysfunction, generate mitochondrial superoxide, and following ferroptosis. TTHM NPs-based photothermal therapy is combined with Sulfasalazine (SUZ), a kind of nonsteroidal anti-inflammatory drugs, to weaken inflammation and promote ferroptosis through suppressing glutamate/cystine (Glu/Cys) antiporter system Xc- (xCT). Additionally, the combination of SUZ with PTT can induce immunogenic cell death (ICD), followed by promoting the maturation of DCs and the attraction of CD8+ T cell, which will secrete IFN-γ and trigger self-amplified ferroptosis via inhibiting xCT and simulating Acyl-CoA synthetase long-chain family member 4 (ACSL4). Moreover, the in vivo results demonstrate that this combination therapy can suppress the expression of inflammatory factors, enhance dendritic cell activation, facilitate T-cell infiltration, and realize effective thermal elimination of primary tumors and distant tumors. In general, this work provides an excellent example of combined medication and stimulates new thinking about onco-therapy and inflammatory response.

Statistical methods to control for confounders in rare disease settings that use external control.

In the drug development for rare disease, the number of treated subjects in the clinical trial is often very small, whereas the number of external controls can be relatively large. There is no clear guidance on choosing an appropriate statistical method to control baseline confounding in this situation. To fill this gap, we conduct extensive simulations to evaluate the performance of commonly used matching and weighting methods as well as the more recently developed targeted maximum likelihood estimation (TMLE) and cardinality matching in small sample settings, mimicking the motivating data from a pediatric rare disease. Among the methods examined, the performance of coarsened exact matching (CEM) and TMLE are relatively robust under various model specifications. CEM is only feasible when the number of controls far exceeds the number of treated, whereas TMLE has better performance with less extreme treatment allocation ratios. Our simulations suggest bootstrap is useful for variance estimation in small samples after matching.

The impact of more restrictive hydrocodone rescheduling on unintentional pediatric opioid exposures.

PURPOSE: To evaluate the impact of rescheduling hydrocodone combination products (HCPs) from schedule III of the Controlled Substances Act to the more restrictive schedule II on unintentional pediatric exposures (≤5 years old). METHODS: Using U.S. data on outpatient retail pharmacy dispensing, emergency department (ED) visits, and poison center (PC) exposure cases, we assessed trends in prescriptions dispensed and unintentional pediatric exposure cases involving hydrocodone (rescheduled from III to II) compared to oxycodone (schedule II) and codeine (schedule III for combination products) using descriptive and interrupted time-series (ITS) analyses during the 16 quarters before and after the October 2014 rescheduling of HCPs. RESULTS: Dispensing of hydrocodone products was declining before rescheduling but declined more steeply post-rescheduling. In ITS analyses, both hydrocodone and oxycodone had significant slope decreases in PC case rates in the post versus pre-period that was larger for hydrocodone, while codeine had a small but significant slope increase in PC case rates. An estimated 4202 ED visits for pediatric hydrocodone exposures occurred in the pre-period and 2090 visits occurred in the post-period, a significant decrease of 50.3%. Oxycodone exposures showed no significant decrease. CONCLUSIONS: Pediatric hydrocodone unintentional exposure ED visits and PC cases decreased after HCP rescheduling more than would be expected had the pre-rescheduling trend continued; the acceleration in the decrease in hydrocodone PC cases was partially offset by a slowing in the decrease in codeine-involved cases. The trend changes were likely due to multiple factors, including changes in dispensing that followed the rescheduling. Unintentional pediatric medication exposures and poisonings remain a public health concern requiring ongoing, multifaceted mitigation efforts.

Reconsideration and Reflection on Spinal Disorders through the Study of Intervertebral Discs in Patients with Lumbar Spondylolisthesis.

OBJECTIVE: This study analyzed and explored the relationship between isthmic spondylolisthesis and disc degeneration by comparing the degree of disc degeneration in patients with isthmic spondylolisthesis, lumbar disc herniation, and asymptomatic healthy individuals. METHODS: This study included a total of 138 cases, consisting of L5-S1 single segment lesion patients and a normal lumbar spine population. The cases were divided into three groups based on the type of disease: 58 cases in the isthmic spondylolisthesis group (IS), 50 cases in the lumbar disc herniation group (LDH), and 30 cases in the normal lumbar vertebrae group (NLV). RESULTS: The research findings indicate that the proportion of intervertebral disc degeneration in the LDH group is significantly higher than that in the IS group and NLV group (65.3% vs. 33.3% vs. 25.8%, P<0.05). The Pfirrmann grades of lumbar intervertebral discs (L1-L4) in the LDH group are significantly higher than those in the IS group and NLV group (P<0.05), and the intervertebral height index (IHI) (L1-L4) of lumbar vertebrae in the LDH group is significantly lower than that in the IS group and NLV group (P<0.05). CONCLUSIONS: The results showed that the degree of intervertebral disc degeneration in patients with isthmic spondylolisthesis was lighter than that in patients with lumbar disc herniation, and even similar to that in healthy individuals. The occurrence of isthmic spondylolisthesis may have slowed down the degeneration of non-affected segment intervertebral discs through certain factors.

Retinoschisin is required for pineal gland calcification and cellular communication in pinealocytes of rats and mice.

Retinoschisin (RS1) is a secretory protein specifically localized to the extracellular domains in both the lateral retina and the pineal gland (PG). However, the functions of RS1 in the pineal body are poorly understood. To address this knowledge gap, in this study, we undertook histochemical, ultrastructural, and western blotting analyses of the PG in rats and RS1-knock-in (RS1-KI) transgenic. We found that RS1 plays a key role in pineal gland calcification (PGC) in mice through both extracellular and intracellular pathways. RS1 was clustered around the cell membrane or intracellularly in pinealocytes, actively participating in the exchange of calcium and thereby mediating PGC. Additionally, RS1 deposition is essential for maintaining PGC architecture in the intercellular space of the adult PG. In RS1-KI mice with a nonsense mutation (p.Y65X) in the Rs1-domain of RS1, the Rs1-domain is chaotically dispersed in pinealocytes and the intercellular region of the PG. This prevents RS1 from binding calcified spots and forming calcified nodules, ultimately leading to the accumulation of calcareous lamellae in microvesicles. Additionally, RS1 was observed to colocalize with connexin-36, thereby modulating intercellular communication in the PG of both rats and mice. Our study revealed for the first time that RS1 is essential for maintaining PGC architecture and that it colocalizes with connexin 36 to modulate intercellular communication in the PG. These findings provide novel insights into the function of the RS1 gene in the PG.

MicroRNA-2285f regulates milk fat metabolism by targeting MAP2K2 in bovine mammary epithelial cells.

In this study, Holstein dairy cows raised in Ningxia were selected as the research object. Mammary epithelial cells (BMECs) were extracted from the milk of eight Holstein cows with significantly different milk fat expression rates and transcribed for sequencing. Bioinformatics analysis was used to analyse the correlation of fat milk percentage, and the critical miR-2285f regulating milk fat was screened out. The target gene binding sites were predicted, and 293T cells and mammary epithelial cells were used as miRNA and target gene models for functional verification in vitro. The tissue difference of miR-2285f Holstein cows was quantitatively analysed by transfecting miR-2285f mimic and inhibitor. Assay (dual luciferase reporter gene assay) and quantitative real-time PCR (quantitative real-time PCR, qRT-PCR), triglyceride (TAG) detection, oil red O detection of lipid droplets, Western Blot assay, Edu and Flow cytometry, The molecular regulatory effects of miR-2285f and target gene MAP2K2 on milk fat metabolism of Holstein dairy cows were studied. The wild-type vector and mutant vector of map2k2-3'utr were constructed, and double luciferase reporting experiments were conducted to verify that MAP2K2 was one of the target genes of miR-2285f. According to qRT-PCR and Western Blot analysis, miR-2285f mainly regulates the expression of MAP2K2 protein in BMECs at the translation level. Bta-miR-2285f can promote cell proliferation and slow cell apoptosis by regulating MAP2K2. Bta-miR-2285f can promote triglyceride (TAG) and lipid droplet accumulation in mammary epithelial cells by targeting MAP2K2. Bta-miR-2285f can regulate protein levels of fat milk marker gene PPARG by targeting MAP2K2. In conclusion, miR-2285f can target the expression of the MAP2K2 gene, promote the proliferation of dairy mammary epithelial cells, inhibit cell apoptosis and regulate the milk fat metabolism in dairy mammary epithelial cells. The results of this study revealed the function of miR-2285f in regulating the differential expression of fat milk in Holstein dairy cows at the cellular level. They provided a theoretical and experimental basis for analysing the regulation network of milk fat synthesis of Holstein dairy cows and the molecular breeding of dairy cows.

Neutral Cyanine: Ultra-Stable NIR-II Merocyanines for Highly Efficient Bioimaging and Tumor-Targeted Phototheranostics.

Fluorescence imaging (FLI)-guided phototheranostics using emission from the second near-infrared (NIR-II) window show significant potential for cancer diagnosis and treatment. Clinical imaging-used polymethine ionic indocyanine green (ICG) dye is widely adopted for NIR fluorescence imaging-guided photothermal therapy (PTT) research due to its exceptional photophysical properties. However, ICG has limitations such as poor photostability, low photothermal conversion efficiency (PCE), short-wavelength emission peak, and liver-targeting issues, which restrict its wider use. In this study, two ionic ICG derivatives are transformed into neutral merocyanines (mCy) to achieve much-enhanced performance for NIR-II cancer phototheranostics. Initial designs of two ionic dyes show similar drawbacks as ICG in terms of poor photostability and low photothermal performance. One of the modified neutral molecules, mCy890, shows significantly improved stability, an emission peak over 1000 nm, and a high photothermal PCE of 51%, all considerably outperform ICG. In vivo studies demonstrate that nanoparticles of the mCy890 can effectively accumulate at the tumor sites for cancer photothermal therapy guided by NIR-II fluorescence imaging. This research provides valuable insights into the development of neutral merocyanines for enhanced cancer phototheranostics.

Effect of Overheating on the Tensile Properties of Nickel-Based Superalloy GH4720Li.

Aero-engines can be exposed to One Engine Inoperative (OEI) conditions during service, and the resulting overheating effect may significantly impact their structural integrity and flight safety. This paper focuses on the influence of overheating on the microstructural evolution and tensile properties of the GH4720Li alloy, a nickel-based polycrystalline superalloy commonly used in turbine disks. Based on the typical OEI operating conditions of a real aero-engine, a series of non-isothermal high-temperature tensile tests involving an OEI stage of 800 °C were conducted. The effects of OEI-induced overheating on the microstructure and tensile properties of the GH4720Li alloy were investigated. The results showed that, after OEI treatment, the primary γ' phase in this alloy was partially dissolved. The GH4720Li superalloy also exhibited numerous microcracks at the grain boundaries, resulting in complex effects on its tensile properties. The alloy's yield strength and ultimate tensile strength were slightly decreased, whereas its ductility decreased considerably. The OEI-induced embrittlement phenomenon was mainly caused by the non-uniform distribution of the tertiary γ' phase within grains. The formation of microcracks nucleated at the interfaces between the primary γ' precipitates and γ matrix phase was another key factor.

Association of circulating long-chain free fatty acids and incident diabetes risk among normoglycemic Chinese adults: a prospective nested case-control study.

BACKGROUND: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVES: Our study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS: This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS: The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18-26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS: These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.