Plasmonic nanosensor and pressure-induced transparency based on coupled resonator in a nanoscale system.

Plasmonic nanosensors and the dynamic control of light fields are of the utmost significance in the field of micro- and nano-optics. Here, our study successfully demonstrates a plasmonic nanosensor in a compact coupled resonator system and obtains the pressure-induced transparency phenomenon for the first time to our knowledge. The proposed structure consists of a groove and slot cavity coupled in the metal-insulator-metal waveguide, whose mechanical and optical characteristics are investigated in detail using the finite element method. Simulation results show that we construct a quantitative relationship among the resonator deformation quantity, the applied pressure variation, and the resonant wavelength offset by combining the mechanical and optical properties of the proposed system. The physical features contribute to highly efficient plasmonic nanosensors for refractive index and optical pressure sensing with sensitivity of 1800 nm/RIU and 7.4 nm/MPa, respectively. Furthermore, the light waves are coupled to each other in the resonators, which are detuned due to the presence of pressure, resulting in the pressure-induced transparency phenomenon. It is noteworthy to emphasize that, unlike previously published works, our numerical results take structural deformation-induced changes in optical properties into account, making them trustworthy and practical. The proposed structure introduces a novel, to the best of our knowledge, approach for the dynamic control of light fields and has special properties that can be utilized for the realization of various integrated components.

New Prospects Arising from Dynamically Crosslinked Polymers: Reprogramming Their Properties.

Dynamically crosslinked polymers (DCPs) have gained significant attention owing to their applications in fabricating (re)processable, recyclable, and self-healable thermosets, which hold great promise in addressing ecological issues, such as plastic pollution and resource scarcity. However, the current research predominantly focuses on redefining and/or manipulating their geometries while replicating their bulk properties. Given the inherent design flexibility of dynamic covalent networks, DCPs also exhibit a remarkable potential for various novel applications through postsynthesis reprogramming their properties. In this review, the recent advancements in strategies that enable DCPs to transform their bulk properties after synthesis are presented. The underlying mechanisms and associated material properties are overviewed mainly through three distinct strategies, namely latent catalysts, material-growth, and topology isomerizable networks. Furthermore, the mutual relationship and impact of these strategies when integrated within one material system are also discussed. Finally, the application prospects and relevant issues necessitating further investigation, along with the potential solutions are analyzed.

Identification of EGR4 as a prospective target for inhibiting tumor cell proliferation and a novel biomarker in colorectal cancer.

EGR4 (Early Growth Response 4) is a member of the EGR family, involving in tumorigenesis. However, the function and action mechanism of EGR4 in the pathogenesis of colorectal cancer (CRC) remain unclear. To address this, we assessed the prognosis of CRC based on EGR4 using the Kaplan-Meier plotter tool and tissue microarray. The abundance of immunoinfiltration was evaluated through ssGSEA, TISIDB, and TIMER. In vitro experiments involving knockdown or overexpression of EGR4 were performed, and RNA-sequencing was conducted to explore potential mechanisms. Furthermore, we used oxaliplatin and 5-fluorouracil to validate the impact of EGR4 on chemo-resistance. Pan-cancer analysis and tissue microarray showed that EGR4 was highly expressed in CRC and significantly correlated with an unfavorable prognosis. Moreover, EGR4 expression was associated with immunoinfiltration and cancer-associated fibroblasts in the CRC microenvironment. Functional enrichment demonstrated that high-expressional EGR4 were involved in chromatin and nucleosome assembly. Additionally, EGR4 promoted the proliferation of CRC cells. Mechanistically, EGR4 upregulated TNFα to activate the NF-κB signaling pathway, and its knockdown reduced p65 nuclear translocation. Importantly, combining shEGR4 with oxaliplatin and 5-fluorouracil significantly inhibited CRC proliferation. Taken together, these findings provide new insights into the potential prognosis and therapeutic targets of EGR4 in CRC.

CD73/adenosine axis exerts cardioprotection against hypobaric hypoxia-induced metabolic shift and myocarditis in a sex-dependent manner.

BACKGROUND: Clinical and experimental studies have shown that the myocardial inflammatory response during pathological events varies between males and females. However, the cellular and molecular mechanisms of these sex differences remain elusive. CD73/adenosine axis has been linked to anti-inflammatory responses, but its sex-specific cardioprotective role is unclear. The present study aimed to investigate whether the CD73/adenosine axis elicits sex-dependent cardioprotection during metabolic changes and myocarditis induced by hypobaric hypoxia. METHODS: For 7 days, male and female mice received daily injections of the CD73 inhibitor adenosine 5'- (α, ß-methylene) diphosphate (APCP) 10 mg/kg/day while they were kept under normobaric normoxic and hypobaric hypoxic conditions. We evaluated the effects of hypobaric hypoxia on the CD73/adenosine axis, myocardial hypertrophy, and cardiac electrical activity and function. In addition, metabolic homeostasis and immunoregulation were investigated to clarify the sex-dependent cardioprotection of the CD73/adenosine axis. RESULTS: Hypobaric hypoxia-induced cardiac dysfunction and adverse remodeling were more pronounced in male mice. Also, male mice had hyperactivity of the CD73/adenosine axis, which aggravated myocarditis and metabolic shift compared to female mice. In addition, CD73 inhibition triggered prostatic acid phosphatase ectonucleotidase enzymatic activity to sustain adenosine overproduction in male mice but not in female mice. Moreover, dual inhibition prostatic acid phosphatase and CD73 enzymatic activities in male mice moderated adenosine content, alleviating glycolytic shift and proinflammatory response. CONCLUSION: The CD73/adenosine axis confers a sex-dependent cardioprotection. In addition, extracellular adenosine production in the hearts of male mice is influenced by prostatic acid phosphatase and tissue nonspecific alkaline phosphatase.

Multiple cystic echinococcosis in abdominal and pelvic cavity treated by surgery with a 4-year follow-up: a case report.

We report a case of a male patient who presented with multiple abdominal and pelvic echinococcosis. The patient had been diagnosed with hepatic echinococcosis for 7 years and developed intermittent distension and discomfort in the upper abdomen after an accidental fall. In recent years, the patient's abdominal distention increased gradually. Computed tomography revealed multiple hydatid cysts in the liver, spleen, abdominal cavity, and pelvic cavity. Abdominal organs were severely compressed, such that he could not eat normally except for a liquid diet. The patient underwent radical surgical resection based on the multi-disciplinary treatment (MDT) and the operation lasted 10 h, nearly 100 hydatid cysts were excised, about 18 liters of cyst fluid and cyst contents were removed, and the patient lost 20 kg of weight after surgery. The operation was successful, but there were still some postoperative complications such as hypovolemic shock, postoperative ascites, postoperative bile leakage. Treatment measures for the patient were anti-infection, antishock, clamping the abdominal drainage tube, and negative pressure abdominal puncture drainage. At follow up the patient's quality of life had been significantly improved with 15 kg weight gain compared to before.

Thermal tuning nanoprinting based on liquid crystal tunable dual-layered metasurfaces for optical information encryption.

Dynamic tuning metasurfaces represent a significant advancement in optical encryption techniques, enabling highly secure multichannel responses. This paper proposes a liquid crystal (LC) tunable dual-layered metasurface to establish a thermal-encrypted optical platform for information storage. Through the screening of unit cells and coupling of characteristics, a dynamic polarization-dependent beam-steering metasurface is vertically cascaded with an angular multiplexing nanoprinting metasurface, separated by a dielectric layer. By integrating high-birefringence LCs into dual-layered metasurfaces, the cascaded meta-system can achieve dynamic thermal-switching for pre-encoded nanoprinting images. This work provides a promising solution for developing compact dynamic meta-systems for customized optical storage and information encryption.

ATP6AP1 as a potential prognostic biomarker in CRC by comprehensive analysis and verification.

The role of ATP6AP1 in colorectal cancer (CRC) remains elusive despite its observed upregulation in pan-cancer. Therefore, the current study aimed to assess the clinical significance of ATP6AP1 and its relationship with the immune infiltration in CRC. Transcriptome data of CRC were obtained from The Cancer Genome Atlas (TCGA) database and analyzed using the combination of R packages and tumor-related databases, including TIMER2, TISIDB, cBioPortal, and MethSurv. The tissue arrays and immunohistochemical staining were performed to verify the expression and clinical characteristics of ATP6AP1. The results revealed that ATP6AP1 expression was significantly elevated in CRC and associated with poor clinicopathological characteristics and prognosis. Furthermore, the analysis demonstrated ATP6AP1 expression was correlated with the infiltration of immune cells and cancer-associated fibroblasts in the microenvironment of CRC. Moreover, ATP6AP1 was found to be linked to various immune checkpoints and chemokines, with enrichment of cytoplasmic vesicle lumen, endopeptidase regulator activity, and endopeptidase inhibitor activity observed in the high ATP6AP1 expressional group. In conclusion, the findings of this study suggest that ATP6AP1 upregulation may serve as a biomarker for poor diagnosis in CRC and offer a potential target for immunotherapy in CRC.

Effects of intermittent cold stimulation on growth performance, meat quality, antioxidant capacity and liver lipid metabolism in broiler chickens.

Intermittent cold stimulation (ICS) enhances broilers' resistance to cold stress. Nonetheless, further research is needed to investigate the underlying mechanisms that enhance cold stress resistance. A total of 160 one-day-old male Ross 308 broilers were randomly divided into 2 groups (CC and CS5), with the CC group managing temperature according to the standard for broiler growth stages, while the CS5 group were subjected to cold stimulation at a temperature 3℃ lower than the CC group for 5 h, every 2 d from 15 to 35 d. Sampling was conducted at 36 d (36D), 50 d (50D) and after acute cold stress for 24 h (Y24). First, we examined the effects of ICS on broiler growth performance, meat quality, antioxidant capacity, and lipid metabolism. The results demonstrated that ICS enhanced the performance of broilers to a certain degree. Specifically, the average weight gain in the CS5 group was significantly higher than that of the CC group, and the feed conversion ratio significantly decreased compared to CC at 4 W and 6 W (P ≤ 0.05). Compared with the CC group, cold stimulation significantly reduced drip loss, shearing force, and yellowness (a* value) of chicken meat, while significantly increased redness (b* value) (P ≤ 0.05). At Y24, the levels of T-AOC and GSH-PX in the serum of the CS5 group were significantly higher than those of the CC group, while the level of MDA was significantly lower (P ≤ 0.05). The content of TG, FFA, and VLDL in the serum of the CS5 group was significantly elevated, whereas the level of TC and HDL was significantly lower (P ≤ 0.05). In addition, we further explored whether AMPK-mTOR pathway is involved in the regulation of changes in lipid metabolism and the possible regulatory mechanisms downstream of the signaling pathway. The results showed that ICS significantly upregulated the expression levels of AMPK mRNA and protein in the liver of the CS5 group at 36D and Y24, while significantly down-regulating mTOR (P ≤ 0.05). Compared with the CC group, ICS significantly down-regulated the mRNA expression levels of lipid synthesis and endoplasmic reticulum stress-related genes (SREBP1c, FAS, SCD, ACC, GRP78 and PERK) at 36D and Y24, while significantly up-regulating the mRNA expression levels of lipid decomposition and autophagy-related genes (PPAR and LC3) (P ≤ 0.05). In addition, at Y24, the protein expression levels of endoplasmic reticulum stress-related genes (GRP78) in the CS5 group were significantly lower, while autophagy-related genes (LC3 and ATG7) were significantly higher (P ≤ 0.05). ICS can affect meat quality and lipid metabolism in broilers, and when broilers are subjected to acute cold stress, broilers trained with cold stimulation have stronger lipid metabolism capacity.

Ethanol extract of Evodia lepta Merr. ameliorates cognitive impairment through inhibiting NLRP3 inflammasome in scopolamine-treated mice.

Evodia lepta Merr. (Evodia lepta) is a well-known traditional Chinese medicine, which has been widely used in herbal tea. We previously reported that the coumarin compounds from the root of Evodia lepta exhibited neuroprotective effects. However, whether Evodia lepta could inhibit NLRP3 inflammasome in dementia was still unknown. In this study, the components of the Evodia lepta extract were identified by HPLC-Q-TOF HRMS. We employed a scopolamine-treated mouse model. Evodia lepta extract (10 or 20 mg/kg) and donepezil were treated by gavage once a day for 14 consecutive days. Following the behavioral tests, oxidative stress levels were measured. Then, Western blot and immunofluorescence analysis were used to evaluate the expressions of NLRP3 inflammasome. 14 major components of the Evodia lepta extract were identified by HPLC-Q-TOF HRMS. The results of Morris water maze, object recognition task and open field test indicated that Evodia lepta extract could ameliorate cognitive impairment in scopolamine-treated mice. Evodia lepta extract improved cholinergic system. Moreover, Evodia lepta extract improved the expressions of PSD95 and BDNF. Evodia lepta extract suppressed neuronal oxidative stress and apoptosis. In addition, Evodia lepta extract inhibited NLRP3 inflammasome in the hippocampus of scopolamine-treated mice. Evodia lepta extract could protect against cognitive impairment by inhibiting NLRP3 inflammasome in scopolamine-treated mice.

Modeling soil loss under rainfall events using machine learning algorithms.

Soil loss is an environmental concern of global importance. Accurate simulation of soil loss in small watersheds is crucial for protecting the environment and implementing soil and water conservation measures. However, predicting soil loss while meeting the criteria of high precision, efficiency, and generalizability remains a challenge. Therefore, this study first used three machine learning (ML) algorithms, namely, random forest (RF), support vector machine (SVM), and artificial neural network (ANN) to develop soil loss models and predict soil loss rates (SLRs). These soil loss models were constructed using field observation data with an average SLR of 1756.48 t/km2 from rainfall events and small watersheds in the hilly-gully region of the Loess Plateau, China. During training, testing and generalizability stages, the average coefficients of determination from the RF, SVM, and ANN models were 0.903, 0.860, and 0.836, respectively. Similarly, the average Nash-Sutcliffe coefficients of efficiency from the RF, SVM and ANN models were 0.893, 0.791 and 0.814, respectively. These results indicated that MLs have superior predictive performance and generalizability, and broad prospects for predicting SLRs. This study also demonstrated that the RF model outperformed better than the SVM and ANN models. Therefore, the RF model was used to simulate the SLR of each small watershed in the Chabagou watershed. Our results showed the four-year (2017-2020) average annual SLR of the small watersheds ranged from 0.73 to 1.63 × 104 t/(km2∙a) in the Chabagou watershed. Additionally, the results also indicated the SLR of small watersheds under the rainstorm event with a 100-year recurrence interval was 4.4-51.3 times that of other rainfall events.Furthermore, this study confirmed that bare land was the predominant source of soil loss in the Chabagou watershed, followed by cropland land and grassland. This study helps to provide the theoretical basis for deploying soil and water conservation measures to realize the sustainable utilization of soil resources in the future.

Evaluation of extravascular lung water and cardiac function in normal vaginal delivery by intrapartum bedside ultrasound.

BACKGROUND: Healthy parturients may experience pulmonary edema and disturbed cardiac function during labor. We aimed to evaluate the extravascular lung water (EVLW), intravascular volume, and cardiac function of normal parturients during spontaneous vaginal delivery by bedside ultrasound. And to explore the correlation between EVLW and intravascular volume, cardiac function. METHODS: This was a prospective observational study including 30 singleton-term pregnant women undergoing spontaneous vaginal delivery. Bedside ultrasound was performed at the early labor, the end of the second stage of labor, 2 and 24 h postpartum, and 120 scanning results were recorded. EVLW was evaluated by the echo comet score (ECS) obtained by the 28-rib interspaces technique. Inferior vena cava collapsibility index (IVC-CI), left ventricle ejection fraction, right ventricle fractional area change, left and right ventricular E/A ratio, and left and right ventricular index of myocardial performance (LIMP and RIMP) were measured. Measurements among different time points were compared, and the correlations between ECS and other measurements were analyzed. RESULTS: During the spontaneous vaginal delivery of healthy pregnant women, 2 had a mild EVLW increase at the early labor, 8 at the end of the second stage of labor, 13 at 2 h postpartum, and 4 at 24 h postpartum (P < 0.001). From the early labor to 24 h postpartum, ECS first increased and then decreased, reaching its peak at 2 h postpartum (P < 0.001). IVC-CI first decreased and then increased, reaching its minimum at the end of the second stage of labor (P < 0.001). RIMP exceeded the cut-off value of 0.43 at the end of the second stage of labor. ECS was weakly correlated with IVC-CI (r=-0.373, P < 0.001), LIMP (r = 0.298, P = 0.022) and RIMP (r = 0.211, P = 0.021). CONCLUSIONS: During spontaneous vaginal delivery, the most vital period of perinatal care is between the end of the second stage of labor and 2 h postpartum, because the risk of pulmonary edema is higher and the right ventricle function may decline. IVC-CI can be used to evaluate maternal intravascular volume. The increase in EVLW may be related to the increase in intravascular volume and the decrease in ventricular function.

The impact of SLC10A3 on prognosis and immune microenvironment in colorectal adenocarcinoma.

BACKGROUND: SLC10A3, a gene upregulated in pan-cancer, lacks full understanding regarding its prognostic implications and association with immune infiltration in colorectal cancer (CRC). This study comprehensively analyzed SLC10A3 in CRC, evaluating its prognostic significance and influence on the tumor's immune microenvironment. METHODS: Transcriptomic data from TCGA were obtained to compare SLC10A3 expression in both colorectal cancer (CRC) and normal tissues. Prognostic value was assessed for overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). DNA methylation patterns of SLC10A3 and correlation with DNA mismatch repair (MMR) were explored. Genetic alterations in SLC10A3 were scrutinized. The study also delved into the influence of SLC10A3 on the immune microenvironment of CRC, including immune cell infiltration and chemokines. Involvement of cancer-associated fibroblasts (CAFs) was explored. Methylation status of specific CpG islands in the SLC10A3 gene correlated with CRC patient prognosis. CRC tissue microarray was performed to verify the expression of SLC10A3 and its relationship with prognosis. RESULTS: The research revealed that SLC10A3 is significantly upregulated in CRC and holds promise as a potential diagnostic marker. Elevated SLC10A3 expression was linked to poorer OS, DSS, and PFI. Methylation patterns of SLC10A3 displayed prognostic relevance, and genetic alterations in the gene were identified. SLC10A3 was shown to impact the immune microenvironment, with significant correlations observed between its expression and various immune cell types, chemokines, and markers associated with CAFs. Furthermore, an inverse relationship between SLC10A3 and MMR molecules was established. Methylation status of specific CpG islands within the SLC10A3 gene was associated with CRC patient prognosis. Tissue microarray showed that SLC10A3 was highly expressed in CRC and significantly correlated with poor prognosis. CONCLUSION: The study underscores the importance of elevated SLC10A3 in CRC, associating it with decreased survival and immune infiltration, proposing it as a diagnostic biomarker and appealing immunotherapy target, given its significant overexpression and influence on the immune microenvironment and prognosis through methylation patterns.

Physiological and Transcriptome Responses of Pinus massoniana Seedlings Inoculated by Various Ecotypes of the Ectomycorrhizal Fungus Cenococcum geophilum during the Early Stage of Drought Stress.

The impact of drought stress on plant growth in arid regions is a critical concern, necessitating the exploration of strategies to enhance plant drought resistance, particularly during the early stages of drought stress. This study focuses on the ectomycorrhizal fungus Cenococcum geophilum, renowned for its extensive genetic diversity and broad host compatibility, making it a crucial ally for host plants facing external stresses. We utilized Pinus massoniana seedlings inoculated with different ecotypic strains of C. geophilum under drought stress. The results showed that the inoculation of most strains of C. geophilum enhanced the drought resistance of P. massoniana seedlings under the early stages of drought stress, by influencing the water content, photosynthesis, accumulation of osmotic adjustment substances, and antioxidant enzyme activities in both shoots and roots of seedlings. Transcriptome analysis showed that mycorrhizal seedlings mainly regulated energy metabolism and reduction-oxidation reaction to resist early drought stress. Notably, the level of drought resistance observed in mycorrhizal seedlings was irrespective of the level of drought tolerance of C. geophilum strains. This study contributes essential data for understanding the drought response mechanisms of mycorrhizal P. massoniana seedlings inoculated by distinct C. geophilum ecotypes and guidance on selecting candidate species of ectomycorrhizal fungi for mycorrhizal afforestation in drought areas.

Effect of High-Frequency Electric Pulse on the Solidification Microstructure and Properties of Hypoeutectic Al-Si Alloy.

The effects of different pulse frequencies on the microstructure grain size and solid solubility of Al-9Si alloy were systematically investigated using OM, SEM, and EDS. The impact on the mechanical properties of the alloy was analyzed using a micro-Vickers hardness tester and multifunctional friction tester. During solidification, the Al-9Si alloy is exposed to high-frequency electric current pulses with a current density of 300 A/cm2 and frequencies of 0 Hz, 500 Hz, 1000 Hz, and 2000 Hz. The experimental results show that the Lorentz force also increases as the high-frequency pulse frequency increases. Intense electromagnetic stirring leads to grain refinement. However, as the pulse frequency continues to grow, the combined effect of Joule heating and Lorentz force results in an enlargement of the melt zone and an increase in grain size. At a pulse frequency of 1000 Hz, the eutectic structure size of the Al-9Si alloy is optimal, with the average size being reduced to 13.87 µm and a dense distribution, effectively eliminating primary Si. The EDS results revealed that the high-frequency pulse led to a more uniform distribution of Si elements within the matrix, and the solid solubility of Si in the α-Al matrix increased to a maximum value of 1.99%, representing a 39.2% increase. At a pulse frequency of 1000 Hz, the sample demonstrates the most favorable mechanical properties, with the friction coefficient reaching a minimum value of 0.302, representing a 37.7% decrease in the average friction coefficient. The results demonstrate that high-frequency pulsing is an effective method for enhancing the mechanical properties of Al-9Si alloy.

Terpene Synthase Gene Family in Chinese Chestnut (Castanea mollissima BL.) Harbors Two Sesquiterpene Synthase Genes Implicated in Defense against Gall Wasp Dryocosmus kuriphilus.

Chinese chestnut (Castanea mollissima BL.) is a well-known fruit tree that has been cultivated in East Asia for millennia. Leaves and buds of the plant can become seriously infested by the gall wasp Dryocosmus kuriphilus (GWDK), which results in gall formation and associated significant losses in fruit production. Herbivore-induced terpenes have been reported to play an important role in plant-herbivory interactions, and in this study, we show that upon herbivory by GWDK, four terpene-related compounds were significantly induced, while the concentrations of these four compounds in intact buds were relatively low. Among these compounds, (E)-nerolidol and (E, E)-α-farnesene have frequently been reported to be involved in plant herbivory defenses, which suggests direct and/or indirect functions in chestnut GWDK defenses. Candidate terpene synthase (TPS) genes that may account for (E)-nerolidol and (E, E)-α-farnesene terpene biosynthesis were characterized by transcriptomics and phylogenetic approaches, which revealed altered transcript levels for two TPSs: CmAFS, a TPS-g subfamily member, and CmNES/AFS, a TPS-b clade member. Both genes were dramatically upregulated in gene expression upon GWDK infestation. Furthermore, Agrobacterium tumefaciens-mediated transient overexpression in Nicotiana benthamiana showed that CmAFS catalyzed the formation of (E, E)-α-farnesene, while CmNES/AFS showed dual (E)-nerolidol and (E, E)-α-farnesene synthase activity. Biochemical assays of the recombinant CmAFS and CmNES/AFS proteins confirmed their catalytic activity in vitro, and the enzymatic products were consistent with two of the major volatile compounds released upon GWDK-infested chestnut buds. Subcellular localization demonstrated that CmAFS and CmNES/AFS were both localized in the cytoplasm, the primary compartment for sesquiterpene synthesis. In summary, we show that two novel sesquiterpene synthase genes CmAFS and CmNES/AFS are inducible by herbivory and can account for the elevated accumulation of (E, E)-α-farnesene and (E)-nerolidol upon GWDK infestation and may be implicated in chestnut defense against GWDK herbivores.

Efficacy of enzyme­induced collagen crosslinking on porcine cornea.

The purpose of the present study was to investigate the effect of a new crosslinking (CXL) method, induced by enzymes, on porcine corneas. Corneal strip (10x3 mm) pairs obtained from 60 fresh porcine eyes were harvested and divided into four groups, Groups A-D. Each pair of corneal strips was incised from the central part of the same cornea; one was incubated in transglutaminase (Tgase) solution (microbial Tgase 2 produced by tissue engineering) and the other remained untreated as a control. CXL strips of Groups A-D were incubated with 2, 1, 0.5 and 0.25 U/ml Tgase solution, respectively at 37˚C for 30 min. After that, tensile strain measurements were performed for all strips. One cornea from each group was chosen randomly for hematoxylin and eosin, and Masson staining to identify histological morphology changes. The elastic modulus of treated corneas of Groups A-D were 6.56±2.93, 4.72±1.29, 5.24±2.13 and 3.48±1.60 MPa (mean ± SD), respectively at a strain of 20%, and had a 66, 43, 36 and -6% increase compared with those of their control strips. Compared with the control strips, the elastic modulus of the treated strips significantly increased in Groups A-C. The central corneal thickness of the treated corneas in Groups A-D were 1.54±0.14, 1.41±0.15, 1.47±0.11 and 1.43±0.13 µm, respectively; however, there was not a statistically significant difference compared with the control group. No reduction in corneal transparency was observed, and no obvious abnormalities were found in corneal morphology. CXL mediated by enzymes can lead to a notable enhancement in the biomechanical characteristics of the cornea while maintaining its structural integrity. Enzyme-induced CXL could be a new generation CXL method for strengthening the cornea.

Intermittent mild cold stimulation alleviates cold stress-induced pulmonary fibrosis by inhibiting the TGF-ß1/Smad signaling pathway in broilers.

To investigate the potential protective effect of intermittent cold stimulation on lung tissues of broilers exposed to acute cold stress (ACS). A total of 384 one-day-old broilers were assigned to 4 experimental groups with 6 replicates of 16 birds each: control (CON) and ACS groups were reared at normal feeding temperature from d 1 to 42; cold treatment groups (CS3+ACS and CS9+ACS) were reared, respectively, at 3°C or 9°C for 5 h on alternate days below the CON group from d 15 to 35. Animals in CS3+ACS, CS9+ACS, and ACS groups were exposed at 10°C for 24 h on d 43. Subsequently, lung tissues were collected to perform histopathological examination and measurement of relevant indexes. The results showed that lung tissues in CS9+ACS and ACS groups exhibited increased inflammatory cell infiltrates and collagen deposition compared to the CON group, while this pathological phenomenon was less pronounced in the CS3+ACS group. Compared to CON group, H2O2 and MDA contents were increased, and the activities of antioxidant enzymes (CAT, SOD, GPx, T-AOC) were reduced in CS9+ACS and ACS group (P < 0.05); mRNA and protein levels of inhibitor of NF-κB, Smad7, matrix metallopeptidase (MMP)-2, MMP9, and antioxidant-related genes were downregulated, whereas mRNA and protein levels of genes related to NF-κB/NLRP3 pathway-regulated inflammation and TGF-ß1/Smad pathway-regulated fibrosis were upregulated in cold-stressed broilers (P < 0.05). mRNA levels of heme oxygenase-1, NAD(P)H quinone oxidoreductase-1, and MMP9 were increased in CS3+ACS group (P < 0.05). Moreover, the expression of most antioxidant-related genes was increased, and that of inflammation- and fibrosis-related genes was reduced in CS3+ACS group (P < 0.05). Therefore, cold stress caused oxidative stress and inflammation, leading to pulmonary fibrosis in broilers, whereas intermittent mild cold stimulation at 3°C below normal rearing temperature alleviated fibrosis by inhibiting the TGF-ß1/Smad pathway modulated by the Nrf2/HO-1 and NF-κB/NLRP3 signaling pathway. This study suggests that intermittent mild cold stimulation can be a potential strategy to reduce ACS-induced lung damage in broilers.

Intermittent cold stimulation affects energy metabolism and improves stress resistance in broiler heart.

To investigate the effect of intermittent cold stimulation on cardiac energy metabolism and cold resistance of broilers, 288 broilers were divided into 3 groups: control group (CC) and 2 cold stimulation groups (CS3 and CS9). The CS3 and CS9 groups received cold stimulation at temperatures of 3°C and 9°C lower than CC group for 5 h from d 15 to 35. Three groups were subjected to acute cold stress (ACS) of 10°C for 12 and 24 h at 44 d. Performance, cardiac histopathological changes, heat shock proteins (HSPs), and lipid metabolism levels were measured. Results showed that the performance was not different among groups at 22 and 29 d (P > 0.05), but the mRNA levels of Acyl CoA synthase long-chain family member 1 (ACSL1) and acyl-coenzyme oxidase (ACO) in CS group were upregulated compared to CC group (P < 0.05). At 36 d, the performance of the CS3 group was better than the other 2 groups, myocardial structure was normal and other lipid metabolism indexes, except for peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) levels, were similar to those of CC group (P > 0.05). The myocardial fiber disorder, Triglyceride (TG), and leptin (LEP) contents were significantly lower in CS9 group than in CC and CS3 groups at 36 d (P < 0.05). The HSP protein levels were significantly higher in CS group than in CC group before ACS (P < 0.05). After 24 h of ACS, the mRNA of lipid metabolism genes, the protein levels of HSP40 and HSP60, and the contents of TG and LEP in the CS3 group were upregulated compared to other groups. The CC and CS9 groups showed myocardial structure was destroyed, with lower TG and LEP levels compared to before ACS (P < 0.05). Therefore, cold stimulation at 3°C lower than the normal feeding temperature for 5 h did not impair performance but can increase the resistance of broilers to ACS by promoting lipid metabolism.

Tanshinone IIA, the key compound in Salvia miltiorrhiza, improves cognitive impairment by upregulating Aß-degrading enzymes in APP/PS1 mice.

In Alzheimer's disease (AD), amyloid-beta (Aß) plays a crucial role in pathogenesis. Clearing Aß from the brain is considered as a key therapeutic strategy. Previous studies indicated that Salvia miltiorrhiza (Danshen) could protect against AD. However, the main anti-AD components in Danshen and their specific mechanisms are not clear. In this study, pharmacological network analysis indicated that Tanshinone IIA (Tan IIA) was identified as the key active compound in Danshen contributing to protect against AD. Then, APP/PS1 double transgenic mice were employed to examine the neuroprotective effect of Tan IIA. APP/PS1 mice (age, 6 months) were administered (10 and 20 mg/kg) for 8 weeks. Tan IIA improved learning and anxiety behaviors in APP/PS1 mice. Furthermore, Tan IIA reduced oxidative stress, inhibited neuronal apoptosis, improved cholinergic nervous system and decreased endoplasmic reticulum stress in the brain of APP/PS1 mice. Moreover, Tan IIA treatment reduced the level of Aß. Molecular docking result showed that Tan IIA might block AD by upregulating Aß-degrading enzymes. Western blot results confirmed that the expressions of insulin degrading enzymes (IDE) and neprilysin (NEP) were significantly increased after Tan IIA treatment, which demonstrated that Tan IIA improved AD by increasing Aß-degrading enzymes.

An interpretable model predicts visual outcomes of no light perception eyes after open globe injury.

BACKGROUND: The visual outcome of open globe injury (OGI)-no light perception (NLP) eyes is unpredictable traditionally. This study aimed to develop a model to predict the visual outcomes of vitrectomy surgery in OGI-NLP eyes using a machine learning algorithm and to provide an interpretable system for the prediction results. METHODS: Clinical data of 459 OGI-NLP eyes were retrospectively collected from 19 medical centres across China to establish a training data set for developing a model, called 'VisionGo', which can predict the visual outcome of the patients involved and compare with the Ocular Trauma Score (OTS). Another 72 cases were retrospectively collected and used for human-machine comparison, and an additional 27 cases were prospectively collected for real-world validation of the model. The SHapley Additive exPlanations method was applied to analyse feature contribution to the model. An online platform was built for real-world application. RESULTS: The area under the receiver operating characteristic curve (AUC) of VisionGo was 0.75 and 0.90 in previtrectomy and intravitrectomy application scenarios, which was much higher than the OTS (AUC=0.49). VisionGo showed better performance than ophthalmologists in both previtrectomy and intravitrectomy application scenarios (AUC=0.73 vs 0.57 and 0.87 vs 0.64). In real-world validation, VisionGo achieved an AUC of 0.60 and 0.91 in previtrectomy and intravitrectomy application scenarios. Feature contribution analysis indicated that wound length-related indicators, vitreous status and retina-related indicators contributed highly to visual outcomes. CONCLUSIONS: VisionGo has achieved an accurate and reliable prediction in visual outcome after vitrectomy for OGI-NLP eyes.