Edge-Rich Pt-O-Ce Sites in CeO2 Supported Patchy Atomic-Layer Pt Enable a Non-CO Pathway for Efficient Methanol Oxidation.

Rational design of efficient methanol oxidation reaction (MOR) catalyst that undergo non-CO pathway is essential to resolve the long-standing poisoning issue. However, it remains a huge challenge due to the rather difficulty in maximizing the non-CO pathway by the selective coupling between the key *CHO and *OH intermediates. Here, we report a high-performance electrocatalyst of patchy atomic-layer Pt epitaxial growth on CeO2 nanocube (Pt ALs/CeO2) with maximum electronic metal-support interaction for enhancing the coupling selectively. The small-size monolayer material achieves an optimal geometrical distance between edge Pt-O-Ce sites and *OH absorbed on CeO2, which well restrains the dehydrogenation of *CHO, resulting in the non-CO pathway. Meanwhile, the *CHO/*CO intermediate generated at inner Pt-O-Ce sites can migrate to edge, inducing the subsequent coupling reaction, thus avoiding poisoning while promoting reaction efficiency. Consequently, Pt ALs/CeO2 exhibits exceptionally catalytic stability with negligible degradation even under 1000 s pure CO poisoning operation and high mass activity (14.87 A/mgPt), enabling it one of the best-performing alkali-stable MOR catalysts.

Superionic Conduction in K3SbS4 Enabled by Cl-Modified Anion Lattice.

All-solid-state potassium batteries emerge as promising alternatives to lithium batteries, leveraging their high natural abundance and cost-effectiveness. Developing potassium solid electrolytes (SEs) with high room-temperature ionic conductivity is critical for realizing efficient potassium batteries. In this study, we present the synthesis of K2.98Sb0.91S3.53Cl0.47, showcasing a room-temperature ionic conductivity of 0.32 mS/cm and a low activation energy of 0.26 eV. This represents an increase of over two orders of magnitude compared to the parent compound K3SbS4, marking the highest reported ionic conductivity for non-oxide potassium SEs. Solid-state 39K magic-angle-spinning nuclear magnetic resonance on K2.98Sb0.91S3.53Cl0.47 reveals an increased population of mobile K+ ions with fast dynamics. Ab initio molecular dynamics (AIMD) simulations further confirm a delocalized K+ density and significantly enhanced K+ diffusion. This work demonstrates diversification of the anion sublattice as an effective approach to enhance ion transport and highlights K2.98Sb0.91S3.53Cl0.47 as a promising SE for all-solid-state potassium batteries.

LRP11-AS1 promotes the proliferation and migration of triple negative breast cancer cells via the miR-149-3p/NRP2 axis.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women. Triple negative breast cancer (TNBC) is the most difficult subtype of breast cancer to treat due to the deficiency in drug-targetable receptors. LRP11-AS1, a newly identified oncogenic long noncoding RNA (lncRNA) was found to be significantly overexpressed in TNBC cells. The aim of this study is to investigate the malignant roles and the oncogenic mechanisms of LRP11-AS1 in TNBC. METHODS: CCK-8, colony formation, transwell migration and transwell invasion assays were performed to study the functions of LRP11-AS1. Quantitative PCR and western blot were used to determine the gene expression. Bioinformatics analysis and dual-luciferase reporter assay were conducted to study lncRNA and miRNA interactions. RESULTS: LRP11-AS1 was found to be significantly overexpressed in TNBC cells compared to the non-TNBC cells and normal mammary epithelial cells. Knockdown of LRP11-AS1 could inhibit the growth and metastasis of TNBC cells and regulate cell cycle. Mechanistically, LRP11-AS1 was found to act as a competing endogenous RNA (ceRNA) to sponge miR-149-3p. Silencing of LRP11-AS1 increased the expression of miR-149-3p and overexpression of miR-149-3p suppressed the expression of LRP11-AS1. Inhibition of miR-149-3p could reverse the anticancer effect of LRP11-AS1 deficiency in TNBC cells. Moreover, Neuropilin-2 (NRP2) was found to be the target of miR-149-3p. Rescue experiments revealed that NRP2 overexpression could rescue the anticancer effect of LRP11-AS1 deficiency in TNBC cells. CONCLUSION: LRP11-AS1 overexpressed in TNBC showed the oncogenic effects possibly by sponging miR-149-3p and regulating the miR-149-3p/NRP2 axis, which indicated LRP11-AS1 as a potential diagnostic biomarker and therapeutic target in TNBC.

Development and application of a fast and efficient CRISPR-based genetic toolkit in Bacillus amyloliquefaciens LB1ba02.

BACKGROUND: Bacillus amyloliquefaciens is generally recognized as food safe (GRAS) microbial host and important enzyme-producing strain in the industry. B.amyloliquefaciens LB1ba02 is a production strain suitable for secreting mesophilic α-amylase in the industry. Nevertheless, due to the low transformation efficiency and restriction-modification system, the development of its CRISPR tool lags far behind other species and strains from the genus Bacillus. This work was undertaken to develop a fast and efficient gene-editing tool in B.amyloliquefaciens LB1ba02. RESULTS: In this study, we fused the nuclease-deficient mutant Cas9n (D10A) of Cas9 with activation-induced cytidine deaminase (AID) and developed a fast and efficient base editing system for the first time in B. amyloliquefaciens LB1ba02. The system was verified by inactivating the pyrF gene coding orotidine 5'-phosphate decarboxylase and the mutant could grow normally on M9 medium supplemented with 5-fluoroorotic acid (5-FOA) and uridine (U). Our base editing system has a 6nt editing window consisting of an all-in-one temperature-sensitive plasmid that facilitates multiple rounds of genome engineering in B. amyloliquefaciens LB1ba02. The total editing efficiency of this method reached 100% and it achieved simultaneous editing of three loci with an efficiency of 53.3%. In addition, based on the base editing CRISPR/Cas9n-AID system, we also developed a single plasmid CRISPR/Cas9n system suitable for rapid gene knockout and integration. The knockout efficiency for a single gene reached 93%. Finally, we generated 4 genes (aprE, nprE, wprA, and bamHIR) mutant strain, LB1ba02△4. The mutant strain secreted 1.25-fold more α-amylase into the medium than the wild-type strain. CONCLUSIONS: The CRISPR/Cas9n-AID and CRISPR/Cas9n systems developed in this work proved to be a fast and efficient genetic manipulation tool in a restriction-modification system and poorly transformable strain.

Effects of dexmedetomidine on glioma cells in the presence or absence of cisplatin.

With the extensive use of dexmedetomidine (Dex) in the surgical resection of tumours for its potent sedative and analgesic properties, its effects on various properties of tumours have received increased attention. The study described herein aimed to investigate the effects of Dex on glioma cells in the presence or absence of cisplatin (DDP). Glioma U251 and U87MG cells were treated with different doses (1-50 nM) of Dex for 12 hours, then recultured in a Dex-free medium. In addition, Dex was added to U251 and U87MG cells 12 hours before or simultaneously with a 12-hour DDP treatment. Treatment with Dex increased the viability of both cell lines; this effect continued for at least 24 hours after Dex was removed. A cell invasion assay indicated that Dex inhibited cell invasion at 50 nM, but not at 10 nM. Western blot analysis showed that Dex increased the expression of phosphorylated extracellular-signal-regulated kinase 1/2, phosphoitide 3-kinase and p-AKT, but decreased ROCK protein levels at a dose of 50 nM. Intracellular Ca 2+ concentration was decreased by Dex in a dose-dependent manner. DDP toxicity was attenuated by 10 nM Dex added either before or with DDP treatment. However, pretreatment with 50 nM Dex instead enhanced the toxicity of DDP. Single-dose treatment with Dex did not significantly change glioma volume in nude mice, but changed the expression of Ki67 and matrix metalloproteinase-3 in the tumour. In conclusion, this study provides evidence of the regulatory effects of Dex on proliferation, invasion and chemosensitivity of glioma cells, and outlines potential mechanisms for these effects.

Optical image encryption based on a joint Fresnel transform correlator with double optical wedges.

An optical cryptosystem based on the joint Fresnel transform correlator (JFTC) with double optical wedges is designed. The designed cryptosystem retains the two major advantages of JTC-based optical cryptosystems. First, the encrypted image is real-valued and therefore is easier to record and transmit. Second, the encryption process is simplified, since it doesn't require accurate alignment of optical elements or the generation of the complex conjugate of the key. Also, the designed optical cryptosystem can produce a decrypted image with higher quality than a JTC-based optical cryptosystem, because the original encrypted image is divided by the Fresnel transform power distribution of the key mask to generate the new encrypted image, which significantly reduces the noise during the decryption process. Simulation results showed that the correlation coefficient of the decrypted image and the original image can reach as large as 0.9819 after denoising and adequately selecting half-central interval a and encrypted image width w. Another improvement relative to JTC-based optical cryptosystems is that the attack resistibility gets enhanced due to the nonlinearity of the encryption process as well as the additional key parameter a, which enlarges the key space.

Efficacy of Cholinesterase Inhibitors in Vascular Dementia: An Updated Meta-Analysis.

BACKGROUND/AIMS: The objective of this study was to determine whether treatment with acetylcholinesterase inhibitors would provide cognitive benefit for patients with vascular dementia. METHODS: Studies in patients with vascular dementia, who had not taken acetylcholinesterase inhibitors or memantine for at least 6 weeks, were included. RESULTS: Twelve studies were included in the final analysis. Donepezil showed significant improvement in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) as compared to placebo, at the doses tested, that is, 5 and 10 mg/day (difference in means -1.389 and -1.680, respectively, p ≤ 0.008), but not on the Mini Mental State Examination (MMSE) (p ≥ 0.259). Galantamine also improved the ADAS-cog in comparison to the placebo (difference in means -2.191, p < 0.001), whereas, rivastigmine did not show any benefit on ADAS-cog. However, the findings with rivastigmine are difficult to interpret, given there were only 2 studies. Treatment with cholinesterase inhibitors was associated with a twofold increase in the odds of discontinuation, due to adverse events (pooled OR 1.966, 95% CI 1.630-2.371, p < 0.001). CONCLUSION: The present results reveal the therapeutic benefits of donepezil and galantamine in patients with vascular dementia. Interestingly, the ADAS-cog and MMSE varied considerably in detecting cognitive improvement.

Resveratrol protects PC12 cells from high glucose-induced neurotoxicity via PI3K/Akt/FoxO3a pathway.

Diabetes is known to be associated with neurodegenerative diseases. Resveratrol, a plant-derived polyphenolic compound found in red wine, possesses antioxidant properties. In this study, we aimed to investigate the effects of resveratrol on the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt)/FoxO3a pathway in mediating high glucose (HG)-induced injuries in neuronal PC12 cells. PC12 cells were exposed to HG to establish a model of HG neurotoxicity. Results showed that pre-treating PC12 cells with resveratrol before exposure to HG led to increased cell viability, decreased apoptotic cells, and reactive oxygen species generation. Western blot analysis showed that HG decreased the phosphorylation of Akt and FoxO3a and led to the nuclear localization of FoxO3a. These effects were significantly alleviated by resveratrol co-treatment. Furthermore, the protective effects of resveratrol were abolished by PI3K/Akt inhibitor LY294002. All these results demonstrate that resveratrol protected the PC12 cells from HG-induced oxidative stress and apoptosis via the activation of PI3K/Akt/FoxO3a signaling pathway.

[Relationship between serum level of uric acid and benign paroxysmal positional vertigo].

OBJECTIVE: To confirm the possible relationships between serum level of uric acid (UA) and benign paroxysmal positional vertigo (BPPV). METHODS: A total of 87 patients with BPPV and 36 age- and gender-matched control subjects were recruited from our hospital between July 1, 2013 and July 1, 2014. All patients underwent a complete audio-vestibular test battery, such as Dix-Hallpike maneuver for posterior semicircular canal and supine roll test for horizontal semicircular canal. All risk factors such as the histories of heart and cerebral vascular diseases, and routine hematological and biochemical analyses were analyzed between two groups. RESULTS: No significant inter-group differences existed in age, gender, histories of hypertension, diabetes mellitus, hyperlipidemia, coronary heart disease, smoking or drinking (P > 0.05). No significant differences existed between systolic blood pressure, diastolic blood pressure, ejection fraction, whole blood count, lipid profile, homocysteine, prealbumin and blood urea nitrogen in patients with BPPV compared with controls (P >0. 05). However, the values of UA (267 ± 86 vs 325 ± 75) µmol/L, hemoglobin ale (5.6 ± 1. 4 vs 6.5 ± 1. 0)%, albumin (36 ± 4 vs 40 ± 4) g/L and creatinine (72 ± 20 vs 81 ± 22) µmol/L were much lower in patients with BPPV versus controls (P < 0. 05). According to multiple Logistic regression model, the lower levels of hemoglobin ale and albumin were independently associated with BPPV (P <0. 05) with the odds ratio of 1. 473 (95% CI 1. 066 - 2. 037) and 1. 162 (95% CI 1. 025 - 1. 318), respectively. However, the level of UA was not independently correlated with the occurrence of BPPV [OR = 1. 005 (95% CI 1. 000 - 1. 011), P =0. 063]. CONCLUSION: The lower levels of hemoglobin alc and albumin are independently associated with BPPV. Although the value of UA is lower in patients with BPPV versus controls, it is not an independent risk factor for BPPV. Due to limited patient data, further studies are needed to clarify the association in a larger sample size of different ethnic groups or longer follow ups.

Generalized 3D registration algorithm for enhancing retinal optical coherence tomography images.

Significance: Optical coherence tomography (OCT) has emerged as the standard of care for diagnosing and monitoring the treatment of various ocular disorders due to its noninvasive nature and in vivo volumetric acquisition capability. Despite its widespread applications in ophthalmology, motion artifacts remain a challenge in OCT imaging, adversely impacting image quality. While several multivolume registration algorithms have been developed to address this issue, they are often designed to cater to one specific OCT system or acquisition protocol. Aim: We aim to generate an OCT volume free of motion artifacts using a system-agnostic registration algorithm that is independent of system specifications or protocol. Approach: We developed a B-scan registration algorithm that removes motion and corrects for both translational eye movements and rotational angle differences between volumes. Tests were carried out on various datasets obtained from two different types of custom-built OCT systems and one commercially available system to determine the reliability of the proposed algorithm. Additionally, different system specifications were used, with variations in axial resolution, lateral resolution, signal-to-noise ratio, and real-time motion tracking. The accuracy of this method has further been evaluated through mean squared error (MSE) and multiscale structural similarity index measure (MS-SSIM). Results: The results demonstrate improvements in the overall contrast of the images, facilitating detailed visualization of retinal vasculatures in both superficial and deep vasculature plexus. Finer features of the inner and outer retina, such as photoreceptors and other pathology-specific features, are discernible after multivolume registration and averaging. Quantitative analyses affirm that increasing the number of averaged registered volumes will decrease MSE and increase MS-SSIM as compared to the reference volume. Conclusions: The multivolume registered data obtained from this algorithm offers significantly improved visualization of the retinal microvascular network as well as retinal morphological features. Furthermore, we have validated that the versatility of our methodology extends beyond specific OCT modalities, thereby enhancing the clinical utility of OCT for the diagnosis and monitoring of ocular pathologies.

Manipulation of d-Orbital Electron Configurations in Nonplanar Fe-Based Electrocatalysts for Efficient Oxygen Reduction.

Manipulation of the spin state holds great promise to improve the electrochemical activity of transition metal-based catalysts. However, the underlying relationship between the nonplanar metal coordination environment and spin states remains to be explored. Herein, we report the precise regulation of nonplanar Fe atomic d-orbital energy level into an irregular tetrahedral crystal field configuration by introducing P atoms. With the increase of P coordination number, the spin magnetic moment decreases linearly from 3.8 µB to 0.2 µB, and the high spin content decreases linearly from 31% to 5%. Significantly, a volcanic curve between the spin states of Fe-based catalysts (Fe-NxPy) and oxygen reduction reaction (ORR) activity has been unequivocally established based on the thermodynamic results. Thus, the Fe-N3P1 catalyst with a 19% medium spin state experimentally exhibits the optimal reaction activity with a high half-wave potential of 0.92 V. These findings indicate that regulating electron spin moments through coordination engineering is a promising catalyst design strategy, providing important insights into spin catalysis.

Highly efficient anion exchange membrane water electrolyzers via chromium-doped amorphous electrocatalysts.

In-depth comprehension and modulation of the electronic structure of the active metal sites is crucial to enhance their intrinsic activity of electrocatalytic oxygen evolution reaction (OER) toward anion exchange membrane water electrolyzers (AEMWEs). Here, we elaborate a series of amorphous metal oxide catalysts (FeCrOx, CoCrOx and NiCrOx) with high performance AEMWEs by high-valent chromium dopant. We discover that the positive effect of the transition from low to high valence of the Co site on the adsorption energy of the intermediate and the lower oxidation barrier is the key factor for its increased activity by synchrotron radiation in-situ techniques. Particularly, the CoCrOx anode catalyst achieves the high current density of 1.5 A cm-2 at 2.1 V and maintains for over 120 h with attenuation less than 4.9 mV h-1 in AEMWE testing. Such exceptional performance demonstrates a promising prospect for industrial application and providing general guidelines for the design of high-efficiency AEMWEs systems.

Steroidal saponin SSPH I induces ferroptosis in HepG2 cells via regulating iron metabolism.

Hepatocellular carcinoma (HCC) is a common type of solid liver carcinoma. Regulating ferroptosis is important for the treatment of HCC. SSPH I is an anti-HCC steroidal saponin isolated from Schizocapsa plantaginea Hance. In this study, we found that SSPH I exerted significant anti-proliferation and anti-migration effects on HepG2 cell, ferroptosis inhibitor ferrostatin-1 or iron chelator ciclopirox partly attenuated the effect of SSPH I. SSPH I also induced apoptosis and G2/M phase cell cycle arrest. ROS accumulation, glutathione depletion and malondialdehyde accumulation were detected after SSPH I treatment, which leads to lipid peroxidation. Ferrostatin-1 or ciclopirox showed a significant antagonist effect towards SSPH I induced lipid peroxidation. Furthermore, typical morphologic changes of ferroptosis, such as increasing density of mitochondrial membrane and reduction of mitochondrial cristae were observed in HepG2 cells after SSPH I treatment. SSPH I does not regulate the xCT protein. Interestingly, SSPH I elevated the expression levels of SLC7A5, which is the negative regulator of ferroptosis. In contrast, SSPH I upregulated the expression of TFR and Fpn proteins, leading to the accumulation of Fe2+. Ferrostatin-1 and ciclopirox presented a similar antagonist effect on SSPH I. In conclusion, our research first reveals that SSPH I induced ferroptosis in HepG2 cells. In addition, our results suggest that SSPH I induces ferroptosis by causing iron overload in HepG2 cells.

Comparison of restrictive and liberal red blood cell suspension transfusion and analysis of influencing factors on prognosis of premature infants.

OBJECTIVE: To investigate the influence of restrictive and liberal red blood cell suspension (RBCs) transfusions on the prognosis of premature infants and to analyze the influencing factors to provide a reference for the transfusion strategy of preterm infants. METHODS: Retrospective analysis was conducted on 85 cases of anemic premature infants treated in our center, including 63 cases in the restrictive transfusion group and 22 in the liberal transfusion group. RESULTS: RBCs transfusions were effective in both groups, and there were no statistically significant differences in post-transfusion hemoglobin and hematocrit between the two groups (P > 0.05). The outcome events: the duration of ventilatory support was statistically prolonger in the restrictive group compared with the liberal group (P < 0.001); however, the differences in mortality, the increased weight before discharge, and length of stay in the hospital within the two groups were not statistically significant (P = 0.237, 0.36 and 0.771, respectively). Univariate survival analysis showed that age, birth weight, Apgar 1 min and Apgar 10 min scores were the influencing factors for death, with P values of 0.035, 0.004, <0.001, and 0.013, respectively; COX regression analysis showed that Apgar 1 min score was an independent factor of the survival time of preterm infants (P = 0.002). CONCLUSION: Compared with the restrictive transfusion group, liberal transfusion patients presented a shorter duration of ventilatory support, which is more beneficial to the prognosis of premature infants.

Limonin mitigates cisplatin-induced acute kidney injury through metabolic reprogramming.

BACKGROUND: Acute kidney injury (AKI) is a known complication of cisplatin administration; currently, there are no effective ways to prevent it. Therefore, it largely limited the use of cisplatin in chemotherapy in the clinic. In this study, we reported that Limonin, a triterpenoid compound extracted from citrus, alleviated cisplatin-induced AKI through metabolic reprogramming in the diseased kidneys. METHODS: Cisplatin was employed to induce AKI in mice. Three groups were set up: Sham, cisplatin + vehicle, and cisplatin + Limonin. Using UHPLC-TOF/MS, we conducted metabolomics to profile the kidneys' endogenous metabolites and metabolic pathways. A network pharmacological method was performed to identify the targets of Limonin on AKI. The human proximal tubular epithelial cell line (HK-2) was applied for in vitro studies. RESULTS: Limonin preserved serum creatinine and blood urea nitrogen levels after cisplatin-induced AKI. Employing metabolomics, we identified 33 endogenous differentially expressed metabolites and 7 significantly disturbed metabolic pathways in the diseased kidneys within three groups. After AKI, Limonin significantly reduced linoleic acid and its downstream product, arachidonic acid, thus exerting a protective effect on the kidney. The network pharmacological method identified CYP3A4 as a key target of Limonin in treating AKI, while CYP3A4 also serve as a mediator of arachidonic acid metabolism. In vitro, Limonin markedly reduced the level of arachidonic acid and HK-2 cell apoptosis triggered by cisplatin, mainly related to the targeted inhibition of CYP3A4-mediated arachidonic acid metabolism. CONCLUSION: Limonin ameliorates cisplatin-induced AKI by inhibiting CYP3A4 activity to regulate arachidonic acid metabolism, ultimately preserving kidney function.

Limonin, a natural ERK2 agonist, protects against ischemic acute kidney injury.

Acute kidney injury (AKI) is a refractory clinical syndrome with limited effective treatments. Amid AKI, activation of the extracellular signal-regulated kinase (ERK) cascade plays a critical role in promoting kidney repair and regeneration. However, a mature ERK agonist in treating kidney disease remains lacking. This study identified limonin, a member of the class of compounds known as furanolactones, as a natural ERK2 activator. Employing a multidisciplinary approach, we systemically dissected how limonin mitigates AKI. Compared to vehicles, pretreatment of limonin significantly preserved kidney functions after ischemic AKI. We revealed that ERK2 is a significant protein linked to the limonin's active binding sites through structural analysis. The molecular docking study showed a high binding affinity between limonin and ERK2, which was confirmed by the cellular thermal shift assay and microscale thermophoresis. Mechanistically, we further validated that limonin promoted tubular cell proliferation and reduced cell apoptosis after AKI by activating ERK signaling pathway in vivo. In vitro and ex vivo, blockade of ERK abolished limonin's capacity of preventing tubular cell death under hypoxia stress. Our results indicated that limonin is a novel ERK2 activator with strong translational potential in preventing or mitigating AKI.

Relationships Between Inflammatory Parameters Derived From Complete Blood Count and Quantitative Flow Ratio in Patients With Stable Coronary Artery Disease.

To investigate the relationships between inflammatory parameters, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII), and quantitative flow ratio (QFR) in stable coronary artery disease (CAD) patients (n = 450) enrolled in this cross-sectional study. Logistic regression was performed to evaluate the associations of NLR, PLR, MLR, and SII evaluated as continuous and binary variables with QFR ≤0.80. When treated as continuous variables, lnNLR was associated with QFR ≤0.80 with borderline significance in univariable (odds ratio (OR) = 1.60, p = .05) and multivariable analysis (OR = 1.72, p = .05), while lnMLR was associated with QFR ≤0.80 significantly in univariable analysis (OR = 1.87, p = .03) and with borderline significance in multivariable analysis (OR = 1.91, p = .05). When treated as binary variables, high levels of MLR and SII were significantly associated with QFR ≤0.80 in univariable (MLR: OR = 1.91, p = .02; SII: OR = 2.42, p = .006) and multivariable analysis (MLR: OR = 1.83, p = .04; SII: OR = 2.19, p = .02). NLR, MLR, and SII, but not PLR, were significantly associated with the severity of coronary physiology in stable CAD patients.

Limonin ameliorates cisplatin-induced acute liver injury by inhibiting 11ß-hydroxysteroid dehydrogenase type 1.

BACKGROUND: Acute liver injury (ALI) is a common side effect of cisplatin treatment in the clinic and can lead to liver failure if not treated promptly. Previous studies have revealed that Limonin, a critical bioactive substance in citrus fruits, can protect multiple organs from various medical conditions. However, whether Limonin could ameliorate cisplatin-induced ALI remains unclear. METHODS: In vivo and in vitro models were induced by cisplatin in the present study. Non-targeted metabolomics was employed to analyze the metabolic changes in the liver after ALI. In addition, molecular docking was utilized to predict the potential targets of Limonin. RESULTS: Limonin attenuated hepatic histopathological injury by reducing hepatocyte apoptosis, lipid peroxidation, and inflammation in cisplatin-challenged mice. Employing metabolomics, we revealed that Limonin mediated the balance of various disturbed metabolic pathways in the liver after cisplatin-induced ALI. Integrating public data mining, molecular docking studies, and in vitro experiments demonstrated that Limonin suppressed the expression and activity of its direct target, 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), in the liver, thus reducing the production of corticosterone (CORT), a key metabolite promoted hepatocyte apoptosis. CONCLUSIONS: Limonin improves the liver metabolic microenvironment by inhibiting 11ß-HSD1 to protect against cisplatin-induced ALI.

A mass spectrometry-based method to screen for α-amidated peptides.

Amidation is a post-translational modification found at the C-terminus of ~50% of all neuropeptide hormones. Cleavage of the C(α)-N bond of a C-terminal glycine yields the α-amidated peptide in a reaction catalyzed by peptidylglycine α-amidating monooxygenase (PAM). The mass of an α-amidated peptide decreases by 58 Da relative to its precursor. The amino acid sequences of an α-amidated peptide and its precursor differ only by the C-terminal glycine meaning that the peptides exhibit similar RP-HPLC properties and tandem mass spectral (MS/MS) fragmentation patterns. Growth of cultured cells in the presence of a PAM inhibitor ensured the coexistence of α-amidated peptides and their precursors. A strategy was developed for precursor and α-amidated peptide pairing (PAPP): LC-MS/MS data of peptide extracts were scanned for peptide pairs that differed by 58 Da in mass, but had similar RP-HPLC retention times. The resulting peptide pairs were validated by checking for similar fragmentation patterns in their MS/MS data prior to identification by database searching or manual interpretation. This approach significantly reduced the number of spectra requiring interpretation, decreasing the computing time required for database searching and enabling manual interpretation of unidentified spectra. Reported here are the α-amidated peptides identified from AtT-20 cells using the PAPP method.

Method for calibrating the fisheye distortion center.

A simple method is proposed to calibrate the fisheye distortion center, which synthesizes the algorithms of the ellipse fitting and gaussian surface fitting. Through analyzing the imaging projection of the equidistant fisheye lens, the calibration principle is introduced in detail. From the experimental results, we find that ellipse fitting error and the relative error of gaussian surface fitting are less than 0.06 pixels and 1.5%, respectively, and the proposed method has a higher calibration precision and stability compared with the methods in the inferences. Besides, the proposed method does not rely on any particular distortion model and other fisheye parameters, and only the image information of the calibration board is utilized, which reduces the calibration complexity and is suitable for the center calibration of any equidistant fisheye camera.