Prevalence, Features and Risk Factors of Macular Retinoschisis in High Myopic Population: the Beijing Eye Study 2011: Macular Retinoschisis in High Myopic Population.

PURPOSE: To investigate the prevalence, features and risk factors of macular retinoschisis (MRS) in highly myopic eyes and their morphological features in Chinese population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: From Beijing Eye Study 2011, a total of 213 highly myopic eyes from 129 participants were included. METHODS: All participants underwent Spectral-domain optical coherence tomography with a macula cube scan of 30°â€¯× 30°centered in the fovea. MAIN OUTCOME MEASURES: High myopia was defined as a refractive error ≤-6 diopters or an axial length ≥ 26.0 mm. MRS presence and its subtypes were assessed based on location and affected retinal layers were evaluated. Prevalence, features and associated factors of MRS and its subtypes in highly myopic population were assessed. RESULTS: Out of 213 highly myopic eyes (129 participants), MRS was observed in 48 eyes, with a prevalence of 22.5% (95%CI: 16.9, 28.6%) per eye, or 36 participants with 27.9% (95% CI: 20.5, 35.7%) per subject. In addition to well-documented factors like older age and higher myopia, the prevalence of MRS was found to be related with a higher intraocular pressure (P=0.013, OR: 1.25; 95%CI: 1.05, 1.48), a thinner subfoveal choroidal thickness (P=0.006 OR: 0.86; 95%CI: 0.77, 0.96), a wider Gamma zone (P=0.003, OR: 1.99; 95%CI: 1.05, 3.11), the presence of glaucoma (P=0.010, OR: 3.37; 95%CI: 1.34, 8.48) and the presence of epiretinal membrane (P=0.023, OR: 3.13; 95%CI: 1.17, 8.36), after multivariate analysis. Eyes with advanced high myopia (P=0.021) and wider gamma zone (P=0.005) were more likely to develop foveal MRS. Eyes with glaucoma tended to have a higher prevalence of outer retinal MRS compared to inner retinal MRS (60.9% versus 36.0%), though the difference was not statistically significant (P=0.06). MRS located in the foveal region or affecting the outer retina was related with a significant worse best corrected visual acuity (BCVA), as compared to MRS that was perifoveally located or affected other regions (P<0.05). CONCLUSIONS: The prevalence of MRS was 27.9% among the elderly highly myopic population. MRS occurring in the foveal region or involving the outer retina demands increased vigilance due to its significant impact on BCVA. The findings contribute to a deeper understanding of MRS, offering insights into its mechanisms and vision prognosis.

Loneliness, Internalizing and Externalizing Problems, and Suicidal Ideation Among Chinese Adolescents: A Longitudinal Mediation Analysis.

PURPOSE: Research indicates that loneliness and emotional and behavioral problems increase the risk of suicidal ideation in adolescents, but less is known about the distinct contributions of these problems. This study aimed to distinguish the pathways through which loneliness, internalizing problems, and externalizing problems contribute to suicidal ideation in Chinese adolescents. METHODS: We did a longitudinal mediation analysis with data collected at 3 time points (2021.05, 2021.10, and 2022.05) from 28 Taizhou high schools. Loneliness and suicidal ideation were assessed using the UCLA 3-Item Loneliness Scale and one suicide item from the Children's Depression Inventory, respectively. The Strength and Difficulties Questionnaire assessed internalizing (emotional and peer problems) and externalizing problems (conduct and hyperactivity problems). Structural equation modeling was used to construct complete longitudinal path models. RESULTS: Using data from 2,190 adolescents in junior and senior high schools, we found that loneliness, internalizing problems, and externalizing problems separately contributed to subsequent higher levels of suicidal ideation. Most notably, loneliness predicted worse subsequent internalizing problems (ß = 0.279, p < .001) and externalizing problems (ß = 0.159, p < .001), which in turn predicted more severe suicidal ideation (ß = 0.019, p < .001; ß = 0.018, p < .001). Loneliness also partially mediated the association between internalizing or externalizing problems and suicidal ideation. DISCUSSION: Loneliness, internalizing problems, and externalizing problems were strongly intertwined with suicidal ideation in adolescents. Public health initiatives could reduce loneliness and emotional and behavioral problems by implementing multifaceted interventions, thereby breaking the vicious circle and protecting against the development of suicidal ideation.

Assessing spatio-temporal heterogeneity and drivers of ecosystem services to support zonal management in mountainous cities.

With complex topography and geomorphology, mountainous cities possess abundant natural resources. They are constrained by ecological environment and topographic conditions, leading to a prominent contradiction between urbanization development and ecological protection. As a result, ecosystem services (ESs) are under greater regulatory pressure. The identification of ecosystem services bundles (ESBs) can be the foundation for developing zonal ecological protection planning policies. We took Chongqing as a case study, investigated the impact mechanisms of socio-ecological factors on the level of ES supply in each ESB. The findings reveal that: (1) The quantitative assessment of ESs for 2000, 2010, and 2020 showed that ESs were temporally stable and spatially heterogeneous. Areas with high supplies of food production (FP) and water yield (WY) were predominantly found in the northwestern cropland and urban built-up regions, whereas high supply areas for the other four ESs were primarily located in the northeastern Dabashan Mountains and the southern Wuling Mountains. (2) The quantification of trade-offs and synergies between ESs showed that FP had a trade-off effect with all five other ESs, while most other ES pairs exhibited synergistic effects. It was found that the interrelationships produced changes over time. (3) Then, three types of ESBs were identified. After examining the influence mechanisms of socio-ecological factors across the three ESBs, individual ESs were found to have essentially the same types of main impact factors in three ESBs, but varies in impact. (4) Finally, with reference to changes in ES levels and interrelationships and the driving mechanisms of socio-ecological factors in each zone, this study proposed zonal strategies for managing ecosystem services and optimizing territorial space based on the geographic characteristics and socio-economic development in different ESBs, with the goal of attaining sustainable urban development and improving human welfare.

The Estimation of Knee Medial Force with Substitution Parameters during Walking and Turning.

PURPOSE: Knee adduction, flexion moment, and adduction angle are often used as surrogate parameters of knee medial force. To verify whether these parameters are suitable as surrogates under different walking states, we investigated the correlation between knee medial loading with the surrogates during walking and turning. METHODS: Sixteen healthy subjects were recruited to complete straight walk (SW), step turn (ST), and crossover turn (CT). Knee joint moments were obtained using inverse dynamics, and knee medial force was computed using a previously validated musculoskeletal model, Freebody. Linear regression was used to predict the peak of knee medial force with the peaks of the surrogate parameters and walking speed. RESULTS: There was no significant difference in walking speed among these three tasks. The peak knee adduction moment (pKAM) was a significant predictor of the peak knee medial force (pKMF) for SW, ST, and CT (p < 0.001), while the peak knee flexion moment (pKFM) was only a significant predictor of the pKMF for SW (p = 0.034). The statistical analysis showed that the pKMF increased, while the pKFM and the peak knee adduction angle (pKAA) decreased significantly during CT compared to those of SW and ST (p < 0.001). The correlation analysis indicated that the knee parameters during SW and ST were quite similar. CONCLUSIONS: This study investigated the relationship between knee medial force and some surrogate parameters during walking and turning. KAM was still the best surrogate parameter for SW, ST, and CT. It is necessary to consider the type of movement when comparing the surrogate predictors of knee medial force, as the prediction equations differ significantly among movement types.

TIM-4 increases the proportion of CD4+CD25+FOXP3+ regulatory T cells in the pancreatic ductal adenocarcinoma microenvironment by inhibiting IL-6 secretion.

BACKGROUND: Currently, creating more effector T cells and augmenting their functions is a focal point in pancreatic ductal adenocarcinoma (PDAC) treatment research. T cell immunoglobulin domain and mucin domain molecule 4 (TIM-4), known for promoting cancer progression in various malignancies, is implicated in the suppressive immune microenvironment of tumors. Analyzing of the role of TIM-4 in the immune regulation of PDAC can offer novel insights for immune therapy. METHODS: We analyzed the TIM-4 expression in tumor specimens from PDAC patients. Meanwhile, multiple fluorescent immunohistochemical staining was used to study the distribution characteristics of TIM-4, and through tissue microarrays, we explored its correlation with patient prognosis. The influence of TIM-4 overexpression on cell function was analyzed using RNA-seq. Flow cytometry and ELISA were used for verification. Finally, the relationship between TIM-4 and T lymphocytes was analyzed by tissue microarray, and the impacts of TIM-4 on T cell subsets were observed by cell coculture technology and a mouse pancreatic cancer in situ model. RESULTS: In PDAC, TIM-4 is mainly expressed in tumor cells and negatively correlated with patient prognosis. TIM-4 influences the differentiation of Treg by inhibiting IL-6 secretion in pancreatic cancer cells and facilitates the proliferation of pancreatic cancer in mice. Additionally, the mechanism may be through the CD8+ effector T cells (CD8+Tc). CONCLUSION: TIM-4 has the potential to be an immunotherapeutic target or to improve the efficacy of chemotherapy for PDAC.

Small GTPase PvARFR2 interacts with cytosolic ABA receptor kinase 3 to enhance alkali tolerance in switchgrass.

Soil alkalization has become a serious problem that limits plant growth through osmotic stress, ionic imbalance, and oxidative stress. Understanding how plants resist alkali stress has practical implications for alkaline-land utilization. In this study, we identified a small GTPase, PvARFR2 (ADP ribosylation factors related 2), that positively regulates alkali tolerance in switchgrass (Panicum virgatum) and uncovered its potential mode of action. Overexpressing PvARFR2 in switchgrass and Arabidopsis (Arabidopsis thaliana) conferred transformant tolerance to alkali stress, demonstrated by alleviated leaf wilting, less oxidative injury, and a lower Na+/K+ ratio under alkali conditions. Conversely, switchgrass PvARFR2-RNAi and its homolog mutant atgb1 in Arabidopsis displayed alkali sensitives. Transcriptome sequencing analysis showed that cytosolic abscisic acid (ABA) receptor kinase PvCARK3 transcript levels were higher in PvARFR2 overexpression lines compared to the controls and were strongly induced by alkali treatment in shoots and roots. Phenotyping analysis revealed that PvCARK3-OE × atgb1 lines were sensitive to alkali similar to the Arabidopsis atgb1 mutant, indicating that PvARFR2/AtGB1 functions in the same pathway as PvCARK3 under alkaline stress conditions. Application of ABA on PvARFR2-OE and PvCARK3-OE switchgrass transformants resulted in ABA sensitivity. Moreover, we determined that PvARFR2 physically interacts with PvCARK3 in vitro and in vivo. Our results indicate that a small GTPase, PvARFR2, positively responds to alkali stress by interacting with the cytosolic ABA receptor kinase PvCARK3, connecting the alkaline stress response to ABA signaling.

Comparing the effect of FUAS and myomectomy on the elasticity of myometrium around targeted uterine fibroid.

BACKGROUND: Focused ultrasound ablation surgery (FUAS) has been widely employed to treat patients with uterine fibroid (UF). This study aimed to estimate myometrial stiffness changes in patients who received FUAS for UFs or myomectomy (ME) and compare the recovery of surrounding myometrium between FUAS and ME groups. Our results may provide more evidence for guiding the proper conception timing in patients with UF. METHODS: This study enrolled 173 patients from May 2022 to August 2023. Shear wave elastography (SWE) was used to dynamically monitor myometrial elasticity changes in patients before and after surgery. Moreover, our study monitored and analyzed the stiffness changes in the targeted fibroid after FUAS, as well as in the myometrium around after FUAS or ME. RESULTS: The stiffness of the myometrium around the resected fibroid was significantly higher than at the preoperative level until 6 months. Conversely, the stiffness of the surrounding myometrium was only temporarily increased 1 day after FUAS. The comparison between FUAS and ME groups regarding the stiffness of the surrounding myometrium showed that nonsignificant differences were detected between the two groups before the treatment. The stiffness of the surrounding myometrium in the ME group was statistically significantly higher than that of the FUAS group 1 day as well as 1, 3, and 6 months after the treatment, respectively. CONCLUSION: The FUAS had less impact on the surrounding myometrium than the ME, which may be more conducive to the recovery of myometrial elasticity in patients with UF.

Activation of PPAR-α attenuates myocardial ischemia/reperfusion injury by inhibiting ferroptosis and mitochondrial injury via upregulating 14-3-3η.

This study aimed to explore the effects of peroxisome proliferator-activated receptor α (PPAR-α), a known inhibitor of ferroptosis, in Myocardial ischemia/reperfusion injury (MIRI) and its related mechanisms. In vivo and in vitro MIRI models were established. Our results showed that activation of PPAR-α decreased the size of the myocardial infarct, maintained cardiac function, and decreased the serum contents of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and Fe2+ in ischemia/reperfusion (I/R)-treated mice. Additionally, the results of H&E staining, DHE staining, TUNEL staining, and transmission electron microscopy demonstrated that activation of PPAR-α inhibited MIRI-induced heart tissue and mitochondrial damage. It was also found that activation of PPAR-α attenuated MIRI-induced ferroptosis as shown by a reduction in malondialdehyde, total iron, and reactive oxygen species (ROS). In vitro experiments showed that intracellular contents of malondialdehyde, total iron, LDH, reactive oxygen species (ROS), lipid ROS, oxidized glutathione disulphide (GSSG), and Fe2+ were reduced by the activation of PPAR-α in H9c2 cells treated with anoxia/reoxygenation (A/R), while the cell viability and GSH were increased after PPAR-α activation. Additionally, changes in protein levels of the ferroptosis marker further confirmed the beneficial effects of PPAR-α activation on MIRI-induced ferroptosis. Moreover, the results of immunofluorescence and dual-luciferase reporter assay revealed that PPAR-α achieved its activity via binding to the 14-3-3η promoter, promoting its expression level. Moreover, the cardioprotective effects of PPAR-α could be canceled by pAd/14-3-3η-shRNA or Compound C11 (14-3-3η inhibitor). In conclusion, our results indicated that ferroptosis plays a key role in aggravating MIRI, and PPAR-α/14-3-3η pathway-mediated ferroptosis and mitochondrial injury might be an effective therapeutic target against MIRI.

Preoperative metabolic syndrome and prognosis after pancreatectomy for pancreatic cancer: A retrospective study.

BACKGROUND: We conducted a retrospective study to investigate the impact of metabolic syndrome (MetS), its individual components, and the number of metabolic risk factors on the prognosis of pancreatic cancer (PC) following pancreatectomy. METHODS: MetS was defined as meeting any three of the following criteria: (1) waist circumference ≥85 cm in men or ≥80 cm in women; (2) triglycerides ≥150 mg/dL or receiving drug treatment for elevated triglycerides; (3) high-density lipoprotein cholesterol <40 mg/dL in men or <50 mg/dL in women or receiving drug treatment for reduced HDL-C; (4) systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg or receiving drug treatment for hypertension; and (5) fasting glucose, (FG) ≥100 mg/dL or receiving drug treatment for elevated glucose. The hazard ratio (HR) and 95% confidence interval (CI) were calculated by the Cox regression model. RESULTS: Six hundred and seven patients who underwent radical resection for PC were enrolled in this study. Among them, 352 patients presented with preoperative MetS. MetS was associated with shorter overall survival (OS) but not with shorter disease-free survival (DFS). The adjusted HR (95% CI) for the poor OS in patients with 3, 4, and 5 metabolic risk components (vs. ≤ 2) were 1.32 (1.03-1.84), 1.64 (1.18-2.29), and 1.96 (1.27-3.04), respectively (p < 0.05). Elevated FG emerged as a significant predictor for poor OS and DFS. CONCLUSIONS: This study highlights that preoperative MetS serves as a significant predictor for OS in patients with PC, with its predictive value escalating as the number of metabolic risk components increases.

In-band pumped, Q-switched thulium-doped fiber laser system delivering 140 W and 7†mJ pulse energy.

We report on a highly efficient, in-band pumped, Q-switched, Tm-doped, rod-type master oscillator power amplifier (MOPA) system delivering up to 140 W average output power and 7 mJ pulse energy with a slope efficiency of 77% at 20 kHz repetition rate. The amplifier is pumped with Raman-shifted fiber lasers centered at 1692 nm. This in-band pump scheme for Tm-doped fiber lasers can significantly mitigate their quantum defect-related heat load limitations. At the same time, this pump wavelength yields a similar amount of storable and extractable energy to the state-of-the-art pumping at 793 nm. This approach has allowed for the development of highly efficient Tm-doped fiber laser systems combining a high average power and a high output pulse energy.

Modified coconut shell biochars (MCSBCs): Fabrication and their adsorptions for Pb(II).

The modified coconut shell biochars (MCSBCs) were fabricated and their adsorptions for Pb(II) were evaluated, in which waste coconut shell was used as the raw material, both ZnCl2 and KMnO4 were applied as the inorganic modifiers. FT-IR spectra, TGA, SEM and BET techniques were utilized to characterize their properties. It was spotted that the thermal stability of UCSBC could arrive at 500 °C. The BET specific surface areas of both Zn- and Mn-modified MCSBCs (485.137, 476.734 m2/g) were highly decreased as compared with that of UCSBC (3528.78 m2/g). In contrast, the average pore diameters of both Zn- and Mn-modified MCSBCs (3.295, 3.803 nm) were smaller than that of UCSBC (3.814 nm). These findings reveal that the modification of CSBC didn't change its pore size. Their adsorptions for Pb(II) were performed and some controlling factors involving pH, contact time, starting concentration and temperature were explored. Moreover, the experiment data were fitted via linear and non-linear techniques. It was found that the Langmuir maximal adsorption amounts of un-modified coconut shell biochar (UCSBC), Zn-modified and Mn-modified MCSBCs for Pb(II) could reach 31.653, 86.547 and 93.666 mg/g, respectively. Two-parameter kinetic models exposed that Pb(II) adsorption on UCSBC, Zn-modified and Mn-modified MCSBCs obeyed both the Lagergren first-order (non-linear R2 = 0.990, 0.954, 0.953, respectively) and Avrami fractional-order (non-linear R2 = 0.989, 0.946, 0.945, respectively) kinetic models. Two-parameter and three-parameter isotherm models verified that Pb(II) adsorption on UCSBC, Zn-modified and Mn-modified MCSBCs followed the Langmuir (non-linear R2 = 0.992, 0.997, 0.993, respectively) as well as Sips (non-linear R2 = 0.992, 0.997, 0.992, respectively) isotherm models. The computation of thermodynamic parameters evidenced that the modification of UCSBC via KMnO4 and ZnCl2 can effectively rise its adsorption for Pb(II), exhibiting promising applications in the handling of metal-bearing water.

Quantitative determination of flow rate variations in reservoir Eco-scheduling: A case study of Yangqu dam in the upper yellow river.

Accurate quantification of flow dynamics during reservoir ecological scheduling hinders the maintenance of normal reproductive activities in downstream riverine fish. This study proposed a quantitative method for determining the flow rate changes in reservoir ecological scheduling. The approach utilized the daily flow rate and daily flow-rate increment to characterize the flow process. Adopting the perspective of shifting spawning grounds of adhesive egg-laying fish species in response to flow rate variations, we introduced the Spawning Ground Overlap Rate as an indicator and utilized it to determine flow rate changes. Focusing on the downstream area of the Yangqu Hydropower Station in the upper reaches of the Yellow River, we calculated the distribution of spawning grounds and the Spawning Ground Overlap Rate in the region. We set a threshold for the Spawning Ground Overlap Rate to restrict the flow rate changes. The results indicated that during the fish spawning period, the ecological flow range in the downstream area of the Yangqu Dam was 480-1200 m3/s. It was required to maintain a daily flow rate change of less than 49.45 m3/(s·d) and a maximum seven-day flow difference of less than 227.76 m3/s to maintain the optimal level of spawning ground overlap rate. Additionally, it was necessary to keep the daily flow rate change below 123.83 m3/(s·d) and the maximum seven-day flow difference below 368.84 m3/s to maintain the minimum spawning ground overlap rate. The findings provide foundational data for determining flow dynamics during the ecological scheduling of the spawning period for viscous-spawning fish.

Amentoflavone attenuates homocysteine-induced neuronal ferroptosis-mediated inflammatory response: Involvement of the SLC7A11/GPX4 axis activation.

Elevated homocysteine (Hcy) levels, referred to hyperhomocysteinemia, are associated with an increased risk of several neurological disorders. Ferroptosis and inflammation play a vital role in Hcy-induced neuronal dysfunction. Amentoflavone (AMF), an active natural biflavone compound, exhibits antioxidative, anti-inflammatory, and neuroprotective activities. This study aimed to explore the potential effects of AMF on Hcy-induced neuronal injury, with a particular focus on the underlying mechanisms involving ferroptosis and inflammation. We assessed neuronal damage in HT22 cells by measuring cell viability, lactate dehydrogenase (LDH) release, and proliferation rates. Additionally, we evaluated oxidative stress markers including the levels of reactive oxygen species (ROS), MitoSOX, mitochondrial membrane potential (MMP), malondialdehyde (MDA), and glutathione (GSH). Iron metabolism and ferroptosis-related gene expressions (Ptgs2, Tfr1, and Fth1) were quantified. TheSLC7A11/GPX4 axis was also detected. Our results showed that AMF treatment dramatically mitigated Hcy-induced neuronal injury by increasing cell viability, decreasing LDH release, and promoting cell proliferation. AMF treatment also reduced Hcy-induced oxidative stress and lipid peroxidation, as evidenced by reduced ROS, MitoSOX, MMP, and MDA levels, along with an increased GSH content in HT22 cells. In addition, AMF treatment reduced iron content and ferroptosis-related gene mRNA levels. However, Erastin, a ferroptosis inducer, blocked these neuroprotective effects of AMF. Ferroptosis inhibitor Ferrostatin-1 also attenuated Hcy-induced ferroptosis. Moreover, both AMF and Ferrostatin-1 effectively mitigated Hcy-induced inflammation, which was again antagonized by Erastin. Mechanistically, AMF treatment enhanced SLC7A11/GPX4 axis in Hcy-treated HT22 cells. In conclusion, these findings suggest that AMF possesses neuroprotection against Hcy-induced injury primarily by inhibiting ferroptosis-mediated inflammation, partly through the activation of SLC7A11/GPX4 axis.

Quantitative Analysis of Hemodynamic Changes in Branch Arteries Covered by Flow Diverters.

BACKGROUND AND OBJECTIVES: Understanding post-treatment hemodynamic alterations and their association with the patency of covered branch arteries is limited. This study aims to identify hemodynamic changes after flow diverter stenting and investigate their correlation with the patency status of covered branch arteries. METHODS: All patients treated with pipeline embolization device for anterior cerebral artery aneurysms at our center between 2016 and 2020 were screened for inclusion. Quantitative digital subtraction angiography was used to analyze changes in hemodynamic parameters pre- and post-stenting. The patency status of covered branch arteries after stenting was categorized as either patent or flow impairment (defined as artery stenosis or occlusion). RESULTS: A total of 71 patients, encompassing 89 covered branch arteries, were enrolled. Flow impairment was observed in 11.2% (10/89) of the branches. The mean transit time and full width at half maximum (FWHM) in covered branches were significantly prolonged post-stenting (P = .004 and .023, respectively). Flow-impaired branch arteries exhibited hemodynamic shifts contrary to those in patent branch arteries. Specifically, flow-impaired branches showed marked reductions in time to peak, FWHM, and mean transit time (decreases of 32.8%, 32.6%, and 29%, respectively; P = .006, .002, and .002, respectively). Further multivariate analysis revealed that reductions in FWHM in the branches (odds ratio = 0.97, 95% CI: 0.95-0.99, P = .007) and smoking (odds ratio = 14.5, 95% CI: 1.39-151.76, P = .026) were independent predictors of flow impairment of covered branches. CONCLUSION: Pipeline embolization device stenting can cause a reduction in blood flow in branch arteries. Compared with patent branches, flow-impaired branches exhibit an increase in blood flow velocity after stenting. Smoking and ΔFWHM in the covered branches indicate flow impairment.

A bimodal time-gated luminescence-magnetic resonance imaging nanoprobe based on a europium(III) complex anchored on BSA-coated MnO2 nanosheets for highly selective detection of H2O2.

A novel nanocomposite, [Eu(BTD)3(DPBT)]-BSA@MnO2, is reported to serve as an effective nanoprobe for bimodal time-gated luminescence (TGL) and magnetic resonance (MR) imaging of H2O2in vitro and in vivo. The nanoprobe was fabricated by immobilizing visible-light-excitable Eu3+ complexes in bovine serum albumin (BSA)-coated lamellar MnO2 nanosheets. The TGL of the Eu3+ complex was effectively quenched by the MnO2 nanosheets. Upon exposure to H2O2, the MnO2 nanosheets underwent reduction to Mn2+, which simultaneously triggered rapid, selective and sensitive "turn-on" responses toward H2O2 in both TGL and MR detection modes. The presence of a protective "corona" formed by BSA enables the nanoprobe to withstand high concentrations of glutathione (GSH), a strong reducing agent of MnO2 nanosheets. This capability allows the nanoprobe to be utilized for detecting H2O2 in living biosamples. The combined utilization of TGL and MR detection modes enables the nanoprobe to image H2O2 across a wide range of resolutions, from the subcellular level to the whole body, without any depth limitations. The results obtained from these modes can be cross-validated, enhancing the accuracy of the detection. The capability of the nanoprobe was validated by TGL imaging of endogenous and exogenous H2O2 in live HeLa cells, as well as bimodal TGL-MR imaging of H2O2 in tumor-bearing mice. The research achievements suggest that the integration of luminescent lanthanide complexes with protein-coated MnO2 nanosheets offers a promising bimodal TGL-MR sensing platform for H2O2in vitro and in vivo.

PGC-1α/LDHA signaling facilitates glycolysis initiation to regulate mechanically induced bone remodeling under inflammatory microenvironment.

The mechanosensitivity of inflammation can alter cellular mechanotransduction. However, the underlying mechanism remains unclear. This study aims to investigate the metabolic mechanism of inflammation under mechanical force to guide tissue remodeling better. Herein, we found that inflammation hindered bone remodeling under mechanical force, accompanied by a simultaneous enhancement of oxidative phosphorylation (OXPHOS) and glycolysis. The control of metabolism direction through GNE-140 and Visomitin revealed that enhanced glycolysis might act as a compensatory mechanism to resist OXPHOS-induced osteoclastogenesis by promoting osteogenesis. The inhibited osteogenesis induced by inflammatory mechanical stimuli was concomitant with a reduced expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). PGC-1α knockdown impeded osteogenesis under mechanical force and facilitated osteoclastogenesis by enhancing OXPHOS. Conversely, PGC-1α overexpression attenuated the impairment of bone remodeling by inflammatory mechanical signals through promoting glycolysis. This process benefited from the PGC-1α regulation on the transcriptional and translational activity of lactate dehydrogenase A (LDHA) and the tight control of the extracellular acidic environment. Additionally, the increased binding between PGC-1α and LDHA proteins might contribute to the glycolysis promotion within the inflammatory mechanical environment. Notably, LDHA suppression effectively eliminated the bone repair effect mediated by PGC-1α overexpression within inflammatory mechanical environments. In conclusion, this study demonstrated a novel molecular mechanism illustrating how inflammation orchestrated glucose metabolism through glycolysis and OXPHOS to affect mechanically induced bone remodeling.

Qingzhuan dark tea polysaccharides-zinc alleviates dextran sodium sulfate-induced ulcerative colitis.

BACKGROUND: Qingzhuan dark tea polysaccharides (QDTP) have been complexed with Zinc (Zn) to form the Qingzhuan dark tea polysaccharides-Zinc (QDTP-Zn) complex. The present study investigated the protective effects of QDTP-Zn on ulcerative colitis (UC) in mice. The UC mouse model was induced using dextran sodium sulfate (DSS), followed by oral administration of QDTP-Zn (0.2 and 0.4 g kg-1 day-1). RESULTS: QDTP-Zn demonstrated alleviation of UC symptoms in mice, as evidenced by a decrease in disease activity index scores. QDTP-Zn also regulated colon tissue injury by upregulating ZO-1 and occludin protein expression, at the same time as downregulating tumor necrosis factor-α and interleukin-6ß levels. Furthermore, QDTP-Zn induced significant alterations in the abundance of bacteroidetes and firmicutes and notably increased levels of short-chain fatty acids (SCFAs), particularly acetic acid, propionic acid, and butyric acid. CONCLUSION: In summary, QDTP-Zn exhibits therapeutic potential in alleviating enteritis by fortifying the colonic mucosal barrier, mitigating inflammation and modulating intestinal microbiota and SCFAs levels. Thus, QDTP-Zn holds promise as a functional food for both the prevention and treatment of UC. © 2024 Society of Chemical Industry.

LINC00152: Potential driver oncogene in pan-cancer.

Long noncoding RNAs (lncRNA) are a class of non-coding RNAs greater than 200 bp in length with limited peptide-coding function. The transcription of LINC00152 is derived from chromosome 2p11.2. Many studies prove that LINC00152 influences the progression of various tumors via promoting the tumor cells malignant phenotype, chemoresistance, and immune escape. LINC00152 is regulated by multiple transcription factors and DNA hypomethylation. In addition, LINC00152 participates in the regulation of complex molecular signaling networks through epigenetic regulation, protein interactions, and competitive endogenous RNA (ceRNA). Here, we provide a systematic review of the upstream regulatory factors of LINC00152 expression level in different types of tumors. In addition, we revisit the main functions and mechanisms of LINC00152 as driver oncogene and biomarker in pan-cancer. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Methods > RNA Analyses in Cells RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.

Integrating historical patterns and future trends for ecological management zone identification and validation: A case study in Beijing, China.

Ecological management zones (EMZs) are pivotal in improving the management of ecosystem services (ESs) and promoting sustainable regional development. In this study, we developed a comprehensive framework aimed at identifying EMZs and substantiating their efficacy through the amalgamation of historical evolutionary patterns and future trends. We applied this framework to Beijing, China, and selected five vital ESs for the study area namely, water yield (WY), carbon sequestration (CS), habitat quality (HQ), soil conservation (SC) and water purification (WP). The framework involves two key components. Firstly, the identification of EMZs is based on the historical evolution of five types of ESs and the dynamic assessment of ES bundles. Subsequently, it enables a simulation of various scenarios to predict future alterations in land use and ESs, thereby validating the effectiveness of the identified EMZs. Our findings reveal notable spatial heterogeneity among different ESs, and that CS, HQ, SC, and WP exhibited synergies, while WY and showed trade-offs with the remaining four types of ESs. Based on an analysis of ES bundle evolution trajectories, we identified four types of EMZs: ecological conservation zone, ecological restoration zone, ecological transition zone and sustainable construction zone. Through strategic EMZ planning, it becomes possible to augment the area of forestland and grassland, alleviate the contradiction between arable land and construction land, and enhance the supply of various ESs. The proposed framework not only offers a novel perspective on the scientific management of ESs but also furnishes decision-makers and planners with an intuitive understanding of the tangible benefits associated with EMZ planning.

Hesperetin ameliorates spinal cord injury in rats through suppressing apoptosis, oxidative stress and inflammatory response.

Spinal cord injury (SCI), a fatal condition, is characterized by progressive tissue degradation and extreme functional deficits with limited treatment options. Hesperetin, a natural flavonoid with potent antioxidant, antiapoptotic and anti-inflammatory properties, has yet to be systematically investigated for its therapeutic effects on neurological damage in rat models of SCI. In this study, rats were given oral hesperetin once daily for 28 days, and their locomotion and histopathological changes were assessed. The findings demonstrated that hesperetin alleviates neurological damage caused by SCI. The observed behavioral improvement could be due to an increase in the survival rate of neurons and oligodendrocytes. This improvement further boosted the ability to repair tissue and form myelin after SCI, ultimately resulting in better neurological outcomes. Furthermore, the present study revealed that hesperetin possesses potent antioxidant capabilities in the context of SCI, reducing the levels of harmful oxygen free radicals and increasing the activity of antioxidant enzymes. Additionally, hesperetin markedly inhibited injury-induced apoptosis, as assessed by caspase-3 immunofluorescence staining and the expression level of caspase-3, indicating the ability of hesperetin to prevent cell death after SCI. Finally, after SCI, hesperetin treatment effectively reduced the expression of inflammatory factors, including IL-1ß, TNFα, and NF-kB, demonstrating the anti-inflammatory effect of hesperetin. Together, our results suggest that hesperetin should be considered a valuable therapeutic aid following SCI, as its positive effects on the nervous system, including antioxidant, anti-inflammatory and antiapoptotic effects, may be crucial mechanisms through which hesperetin exerts neuroprotective effects against SCI.