Tunable circularly polarized luminescence behaviors caused by the structural symmetry of achiral pyrene-based emitters in chiral co-assembled systems.

The regulation of circularly polarized luminescence (CPL) behavior is of great significance for practical applications. Herein, we deliberately designed three achiral pyrene derivatives (Py-1, Py-2, and Py-3) with different butoxy-phenyl substituents and the chiral binaphthyl-based inducer (R/S-B) with anchored dihedral angle to construct chiral co-assemblies, and explored their induced CPL behaviors. Interestingly, the resulting co-assemblies demonstrate tunable CPL emission behaviors caused by the structural symmetry effect of achiral pyrene-based emitters during the chiral co-assembly process. And in spin-coated films, the dissymmetry factor (gem) values were 9.1 × 10-3 for (R/S-B)1-(Py-1)10, 5.6 × 10-2 for (R/S-B)1-(Py-2)7, and 8.6 × 10-4 for (R/S-B)1-(Py-3)1, respectively. The strongest CPL emission (|gem| = 5.6 × 10-2, λem = 423 nm, QY = 34.8 %) was detected on (R/S-B)1-(Py-2)7 due to the formation of regular and ordered helical nanofibers through the strong π-π stacking interaction between the R/S-B and the achiral Py-2 emitter. The strategy presented here provides a creative approach for progressively regulating CPL emission behaviors in the chiral co-assembly process.

Lactiplantibacillus plantarum-encapsulated microcapsules prepared from okra polysaccharides improved intestinal microbiota in Alzheimer's disease mice.

Background: Okra contains a viscous substance rich in water-soluble material, including fibers, pectin, proteoglycans, gum, and polysaccharides. This study explored the use of okra polysaccharides by microorganisms and their potential to improve microbiota. Methods: The regulation of microcapsules prepared from okra polysaccharides with or without L. plantarum encapsulation on intestinal microbiota was assessed through 16S metagenomic analysis and short-chain fatty acids (SCFAs) in AppNL-G-F/NL-G-F mice (Alzheimer's disease; AD model). Results: We found that Lactobacillaceae and Lactobacillus were majorly regulated by microcapsules prepared from okra polysaccharides in AD mice. Similarly, microcapsules prepared from okra polysaccharides with L. plantarum encapsulation markedly elevated the abundance of Lactobacillaceae and Lactobacillus and increased SCFAs in AD mice. Conclusion: Our results suggest that microcapsules prepared from okra polysaccharides with or without L. plantarum encapsulation may improve intestinal microbiota by elevating Lactobacillus levels in AD mice.

ATG5 nonautophagically regulates inflammation and differentiation in mouse embryonic stem cells.

Embryonic stem cells (ESCs), with abilities of infinite proliferation (self-renewal) and to differentiate into distinct cell types (pluripotency), show attenuated inflammatory response against cytokines or pathogens, which is recognized as a unique characteristic of ESCs compared with somatic cells. However, the underlying molecular mechanisms remain unclear, and whether the attenuated inflammatory state is involved in ESC differentiation is completely unknown. Our recent study demonstrated that macroautophagy/autophagy-related protein ATG5 inhibits the inflammatory response of mouse ESCs (MmESCs) by promoting the degradation of BTRC/ß-TrCP1 and further the downregulation of NFKB/NF-κB signaling. In addition, maintenance of an attenuated inflammation status in MmESCs is required for their differentiation. In conclusion, ATG5 is a key regulator for the regulation of inflammatory response and differentiation of MmESCs.

3D-QSAR and Molecular Dynamics Study of Isoxazole Derivatives to Identify the Structural Requirements for Farnesoid X Receptor (FXR) Agonists.

The farnesoid X receptor (FXR) has been recognized as a potential drug target for the treatment of non-alcoholic fatty liver disease (NAFLD). FXR agonists benefit NAFLD by modulating bile acid synthesis and transport, lipid metabolism, inflammation, and fibrosis pathways. However, there are still great challenges involved in developing safe and effective FXR agonists. To investigate the critical factors contributing to their activity on the FXR, 3D-QSAR molecular modeling was applied to a series of isoxazole derivatives, using comparative molecular field analysis (CoMFA (q2 = 0.664, r2 = 0.960, r2pred = 0.872)) and comparative molecular similarity indices analysis (CoMSIA (q2 = 0.706, r2 = 0.969, r2pred = 0.866)) models, which demonstrated strong predictive ability in our study. The contour maps generated from molecular modeling showed that the presence of hydrophobicity at the R2 group and electronegativity group at the R3 group in these compounds is crucial to their agonistic activity. A molecular dynamics (MD) simulation was carried out to further understand the binding modes and interactions between the FXR and its agonists in preclinical or clinical studies. The conformational motions of loops L: H1/H2 and L: H5/H6 in FXR-ligand binding domain (LBD) were crucial to the protein stability and agonistic activity of ligands. Hydrophobic interactions were formed between residues (such as LEU287, MET290, ALA291, HIS294, and VAL297) in helix H3 and ligands. In particular, our study found that residue ARG331 participated in salt bridges, and HIS447 participated in salt bridges and hydrogen bonds with ligands; these interactions were significant to protein-ligand binding. Eight new potent FXR agonists were designed according to our results, and their activities were predicted to be better than that of the first synthetic FXR agonist, GW4064.

Design and application of a novel "turn-on" fluorescent probe for imaging sulfite in living cells and inflammation models.

Sulfite is one of the main existing forms of sulfur dioxide (SO2) in living system, which has been recognized as an endogenous mediator in inflammation. Evidence has accumulated to show that abnormal level of sulfite is associated with many inflammatory diseases, including neurological diseases and cancers. Herein, a novel fluorescent probe named QX-OA was designed and synthesized to detect sulfite. QX-OA was constructed by choosing quinolinium-xanthene as the fluorophore and levulinate as the specific and relatively steady recognition reaction. The probe showed remarkable green turn-on signal at 550 nm, together with high sensitivity (90-fold) and excellent selectivity to sulfite over other possible interfering species. In the meantime, QX-OA was successfully applied to visualize endogenous and exogenous sulfite in Hela cells. In the LPS-induced inflammation model, QX-OA could visualize the dose-dependent increase of sulfite level (0-2 mg/mL). Consequently, QX-OA was determined to be a potential method for detecting sulfite in pre-clinical diagnosis.

Infrared Nanoimaging of Hydrogenated Perovskite Nickelate Memristive Devices.

Solid-state devices made from correlated oxides, such as perovskite nickelates, are promising for neuromorphic computing by mimicking biological synaptic function. However, comprehending dopant action at the nanoscale poses a formidable challenge to understanding the elementary mechanisms involved. Here, we perform operando infrared nanoimaging of hydrogen-doped correlated perovskite, neodymium nickel oxide (H-NdNiO3, H-NNO), devices and reveal how an applied field perturbs dopant distribution at the nanoscale. This perturbation leads to stripe phases of varying conductivity perpendicular to the applied field, which define the macroscale electrical characteristics of the devices. Hyperspectral nano-FTIR imaging in conjunction with density functional theory calculations unveils a real-space map of multiple vibrational states of H-NNO associated with OH stretching modes and their dependence on the dopant concentration. Moreover, the localization of excess charges induces an out-of-plane lattice expansion in NNO which was confirmed by in situ X-ray diffraction and creates a strain that acts as a barrier against further diffusion. Our results and the techniques presented here hold great potential for the rapidly growing field of memristors and neuromorphic devices wherein nanoscale ion motion is fundamentally responsible for function.

An Intensity-Demodulated Fiber-Optic Magnetometer Based on Nanostructured Magnetic Fluid-Filled Fluidic Photonic Crystal Fibers.

An intensity-demodulated fiber-optic magnetometer is proposed and experimentally investigated, which is fabricated via fusion splicing a segment of photonic crystal fiber (PCF) between single-mode fibers (SMFs), with the cladding air holes of PCF filled with magnetic fluid. Using the magneto-optical properties of the magnetic fluid, the transmission spectrum is changed with an external magnetic field. Based on the intensity variations in the transmission spectrum, the magnetic field is detected, and a sensitivity of 0.238 dB/mT is obtained at 1550.03 nm with the length of PCF 5.5 cm. By converting light signals into electrical signals, a sensitivity of 0.003 V/mT is achieved. The fiber-optic magnetometer possesses the advantages of simple fabrication, compact/robust structure, and low cost.

IDH-mutant grade 4 astrocytoma: a comparison integrating the clinical, pathological, and survival features between primary and secondary patients.

OBJECTIVE: IDH-mutant grade 4 astrocytomas (AIDHmut/G4) are divided into primary de novo (pAIDHmut/G4) and secondary with a history of prior lower-grade gliomas (LGGs; sAIDHmut/G4). The mutational spectrum and DNA methylation patterns are homogeneous within de novo pAIDHmut/G4 and evolved sAIDHmut/G4, but the two groups have different diagnoses, management, and outcomes. This study sought to systematically compare the clinical, pathological, and survival characteristics between them. METHODS: Of the 871 grade 4 astrocytomas with data for IDH mutation, 698 (80.1%) were primary and 173 (19.9%) were secondary. Of the 698 primary tumors, 103 (14.8%) were pAIDHmut/G4, and of the 173 secondary tumors, 108 (62.4%) were sAIDHmut/G4. Clinical, pathological, and survival features were compared between pAIDHmut/G4 and sAIDHmut/G4. Multivariate analyses were performed to identify prognostic factors. RESULTS: Patients with sAIDHmut/G4 had significantly shorter median overall survival (OS; 11.8 vs 34.2 months, hazard ratio [HR] 2.69, 95% confidence interval [CI] 1.367-5.306, p = 0.004) and progression-free survival (PFS; 8.5 vs 24.3 months, HR 2.83, 95% CI 1.532-5.235, p = 0.001) than patients with pAIDHmut/G4. In patients with sAIDHmut/G4, resection status and chemotherapy were independent prognostic factors for OS and PFS; in patients with pAIDHmut/G4, LGG component, resection status, and O6-methylguanine DNA methyltransferase promoter methylation were independent prognostic factors. The therapeutic strategies of LGGs did not influence survival of patients with sAIDHmut/G4, but patients who had not received radiotherapy or chemotherapy when they were diagnosed with LGGs were found to benefit from radiotherapy or chemotherapy when they progressed to sAIDHmut/G4. CONCLUSIONS: The different clinical characteristics, survival, and risk factors between sAIDHmut/G4 and pAIDHmut/G4 provide a reference to guide treatment decisions in AIDHmut/G4.

Efficacy of indocyanine green fluorescence-guided inguinal lymph node dissection for penile cancer: a randomised trial.

OBJECTIVES: To investigate the safety and efficacy of indocyanine green (ICG) fluorescence-guided inguinal lymph node dissection (ILND) in patients with penile cancer. PATIENTS AND METHODS: A prospective, single-blind, randomised controlled clinical trial (ChiCTR2100044584) was performed among patients with penile caner who underwent bilateral modified ILND at four centres in China between 1 April 2021 and 30 June 2022. Patients aged 18-80 years and diagnosed with squamous cell carcinomas were included. Each enrolled patient was randomly assigned to either ICG fluorescence-guided ILND by a laparoscopic or robot-assisted approach in one groin, with non-ICG fluorescence-guided ILND in the other groin acting as a control. The primary outcome was the number of retrieved ILNs. Secondary outcomes included complications according to the Clavien-Dindo classification and the ILN non-compliance (inadequate removal of ILNs) rate. RESULTS: A total of 45 patients were included in the intention-to-treat (ITT) analysis, and the 42 who completed the entire study were included in the per protocol (PP) analysis. There were no ICG-related complications in any of the patients. The results of the ITT and PP analyses indicated that the total number of unilateral ILNs retrieved was higher on the ICG side than on the non-ICG side (mean 13 vs 9 ILNs, difference 4 ILNs [95% CI 2.7-4.4], P = 0.007), and the number of unilateral deep and superficial ILNs was higher on the ICG side. Furthermore, the LN non-compliance rate was lower on the ICG side than on the non-ICG side. Additionally, there was no significant difference in local complications in the groins between the two sides (P > 0.05). CONCLUSION: An ICG fluorescence-guided ILND was safe for patients with penile cancer. This procedure can improve the number of ILNs retrieved and reduce the LN non-compliance rate without increased complications. ICG fluorescence-guided ILND is beneficial and recommended for selected patients with penile cancer.

Advantages of computed tomography-based navigation in clipping distal anterior cerebral artery aneurysms: a retrospective cohort study.

Background: The occurrence rate of distal anterior cerebral artery (DACA) aneurysms is relatively low, primarily due to their deep-seated location, which makes surgical clamping challenging. The objective of this study was to investigate the efficacy and safety of computed tomography (CT) navigation-assisted clipping of DACA aneurysms compared to traditional clipping without navigation. Methods: A retrospective cohort study involving retrospective data collection was performed. The retrospective analysis was conducted on 139 patients with ruptured DACA aneurysms who underwent clipping. From January 2013 to November 2021, 164 patients were retrieved at the Department of Neurosurgery, Renmin Hospital of Wuhan University. The inclusion criteria were patients diagnosed with DACA aneurysms via CT angiography (CTA) or digital subtraction angiography (DSA), those with complete clinical data, and those who underwent craniotomy for aneurysm clipping. Meanwhile, the exclusion criteria were as follows: aneurysm recurrence, traumatic brain injury or surgery history, blood disorders or recent anticoagulant use, and severe organ dysfunction. Data on gender, age, Hunt-Hess grade, Fisher grade, modified Rankin Scale (mRS) score, aneurysm location, hospitalization time, aneurysm found time (the duration from incision to aneurysm discovery), and intraoperative bleeding volume were collected from medical records and neurosurgical databases. Patients were followed up in the clinic or by telephone in May 2022. All patients were divided into a navigation group or a traditional group for statistical analysis. Results: No statistically significant differences were observed in age, sex, Fisher grade, Hunt-Hess grade, hospitalization time, or aneurysm site between the navigation group and traditional group (P>0.05). Intraoperative blood loss was lower in the navigation group than in the traditional group {370 [280-460] vs. 430 [310-610] mL, P=0.045}. Patients in the traditional group had a shorter aneurysm found time than did those in the navigation group {49 [42-53] vs. 79 [63-84] min, P<0.001}. There was no significant difference in the mRS score at hospital discharge (P=0.336) or follow-up (P=0.157) between the two groups. Conclusions: CT neuronavigation-assisted microsurgery for clipping DACA aneurysms may improve surgical accuracy, shorten the time to locate aneurysms, and reduce intraoperative blood loss. Although no significant difference in prognosis was observed, this technique shows promise as a safe and effective alternative to traditional clipping without navigation.

Optical Fiber Sensing-Aided 3D-Printed Replacement Parts for Enhancing the Sensing Ability of Architectural Heritage.

This study discussed the application of optical fibers in addressing the problem of insufficient light harvesting and sensing health monitoring in ancient buildings. Based on three-dimensional (3D) printing technology to fix the light-harvesting lens and conducting optical fiber, develop the replacement parts that can be buried into the optical fiber of ancient buildings. By introducing the experimental application to improve the experimental quality of research and teaching. Firstly, it highlights the advantage that the optical fiber plus lens structure design can make the natural light introduced for a long time; secondly, it points out that the buried optical fiber structure design does not affect the warmth and sound insulation of the building; finally, the health monitoring of the building is realized through the proposed method of buried optical fiber sensing. The design scheme adopts a fiber optic light transmission and sensing system, which can realize the whole system's corrosion resistance, after laying buried and low-cost operation.

[Preparation and quality evaluation of total flavonoids microemulsion of "Pueraria lobata-Hovenia dulcis"].

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.

CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathway.

C-X-C chemokine receptor type 4 (CXCR4) is critical for homeostasis of the adaptive and innate immune system in some CNS diseases. Bruton's tyrosine kinase (BTK) is an essential kinase that regulates inflammation in immune cells through multiple signaling pathways. This study aims to explore the effect of CXCR4 and BTK on neuroinflammation in the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Our results showed that the expression of CXCR4 and p-BTK increased significantly at 24 h after SAH in vivo and in vitro. Ibrutinib improved neurological impairment, BBB disruption, cerebral edema, lipid peroxidation, neuroinflammation and neuronal death at 24 h after SAH. Inhibition of BTK phosphorylation promoted the in vitro transition of hemin-treated proinflammatory microglia to the anti-inflammatory state, inhibited the p-P65 expression and microglial pyroptosis. NLRP3 deficiency can significantly reduce pyroptosis in SAH mice. Moreover, CXCR4 inhibition can suppress NLRP3-mediated pyroptosis, NF-κB activation and NOX2 expression in vitro, and ibrutinib can abolish CXCR4-aggravated BBB damage and pyroptosis in EBI after SAH. The levels of CXCR4 in CSF of SAH patients is significantly increased, and it is positively correlated with GSDMD and IL-1ß levels, and have a moderate diagnostic value for outcome at 6-month follow-up. Our findings revealed the effect of CXCR4 and P-BTK on NLRP3-mediated pyroptosis and lipid peroxidation after SAH in vivo and in vitro, and the potential diagnostic role of CXCR4 in CSF of SAH patients. Inhibition of CXCR4-BTK axis can significantly attenuate NLRP3-mediated pyroptosis and lipid peroxidation by regulating NF-κB activation in EBI after SAH.

Synthesis and Bioevaluation of 3-(Arylmethylene)indole Derivatives: Discovery of a Novel ALK Modulator with Antiglioblastoma Activities.

Glioblastoma is the most common brain tumor, with high recurrence and low survival rates. An integrative bioinformatics analysis demonstrated that anaplastic lymphoma kinase (ALK) is a promising therapeutic target for glioblastoma. We designed and synthesized a series of 3-(arylmethylene)indole derivatives, which were further evaluated for antiproliferative activity using glioma cell lines. Among them, compound 4a significantly inhibited the viability of glioblastoma cells. With favorable pharmacokinetic characteristics and blood-brain barrier permeability, 4a improved the survival rate and inhibited the growth of orthotopic glioblastoma. The Phospho-Totum system revealed that ALK was a potential target for the antiglioblastoma activity of 4a. Further experiments indicated that 4a might be a novel ALK modulator, which interacted with the extracellular ligand-binding domain of ALK, thus selectively induced ERK-mediated autophagy and apoptosis. Our findings provide an alternative ALK-based targeting strategy and a new drug candidate for glioblastoma therapy.

Could the New pN Staging Classification Better Predict the Prognosis of Penile Cancer? A Population-Based Analysis.

BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) has made new revisions to the N staging of penile cancer (PeCa). This study aimed to evaluate the prognostic value of the new N staging classification. METHODS: This cohort was included from the Surveillance, Epidemiology, and End Results (SEER) database (1988-2016). Overall survival (OS) and cancer-specific survival (CSS) were evaluated using Kaplan-Meier survival curve. The Cox proportional hazards model was employed to calculate hazard ratio (HR) and 95% confidence intervals (CI). RESULTS: Among the included 583 patients, 270 patients had only one positive inguinal lymph node (ILNP), 115 had two ILNPs, and 198 had 3 or more ILNPs. Kaplan-Meier analysis indicated that The OS and CSS of patients with ILNP = 2 were not statistically different from those with ILNP = 1 (p = 0.394; p = 0.760), but had OS and CSS benefit over those with ILNP ≥3 (p = 0.017; p = 0.020). Cox proportional hazards regression analysis indicated that patients with ILNP = 2 and ILNP = 1 have similar OS and CSS (HR = 0.80, p = 0.153; HR = 0.74, p = 0.148), but patients with ILNP ≥3 had worse OS and CSS than patients with ILNP = 2 (HR = 1.56, p = 0.007; HR = 1.86, p = 0.003). CONCLUSIONS: PeCa patients with only one or two lymph node metastases had similar survival outcomes. AJCC 8th edition pN staging has a better discriminative ability to predict the prognosis and can accurately stratify mortality risk in PeCa.

A Flexible Pressure Sensor Based on Graphene/Epoxy Resin Composite Film and Screen Printing Process.

At present, flexible pressure-sensitive materials generally have problems with weak adhesion and poor wear resistance, which easily result in friction failure when used for plantar pressure detection. In this study, a flexible pressure sensor with the advantages of a wide detection range, fast recovery, and good abrasive resistance was designed and prepared based on the screen printing process. The pressure-sensitive unit with a structural size of 5 mm× 8 mm was a functional material system due to the use of graphene and epoxy resin. The influence of the different mass ratios of the graphene and epoxy resin on the sensing properties was also studied. The test results showed that when the mass ratio of graphene to epoxy resin was 1:4, the response time and recovery time of the sensing unit were 40.8 ms and 3.7 ms, respectively, and the pressure detection range was 2.5-500 kPa. The sensor can detect dynamic pressure at 0.5 Hz, 1 Hz, 2 Hz, 10 Hz, and 20 Hz and can withstand 11,000 cycles of bending. In addition, adhesion tests showed that the high viscosity of the epoxy helped to improve the interlayer bond between the pressure-sensitive materials and the flexible substrate, which makes it more suitable for plantar pressure detection environments, where friction is common.

Effects of the Oat Hay Feeding Method and Compound Probiotic Supplementation on the Growth, Antioxidant Capacity, Immunity, and Rumen Bacteria Community of Dairy Calves.

This study aimed to investigate the effects of the oat hay feeding method and compound probiotics (CMP) on the growth, health, serum antioxidant and immune indicators, rumen fermentation, and bacteria community of dairy calves from 3 to 5 months of age. Forty-eight female Holstein calves (80 ± 7 days of age, 93.71 ± 5.33 kg BW) were selected and randomly divided into four groups. A 2 × 2 factorial design was adopted for the experiment, with the factors of the oat hay feeding method (fed as free-choice or 16.7% in the diet) and compound probiotics (CMP) inclusion (0.15% or 0%) in the pelleted starter. The results showed that, compared with giving oat hay as free-choice, feeding a diet of 16.7% oat hay increased the pelleted starter intake at 1-84 d (p < 0.05), with an average daily gain (ADG) at 61-84 d (p = 0.02); adding CMP to the pelleted starter did not significantly affect body weight, and reduced the fecal index (p < 0.05). Feeding 16.7% oat hay increased the concentration of IgA, IgG, and IgM (p < 0.01), while adding CMP increased the catalase (p < 0.01) and decreased the concentration of malondialdehyde (p < 0.01) in serum. Feeding 16.7% oat hay increased the ruminal concentration of propionic acid (p < 0.05) and isobutyric acid (p = 0.08), and decreased the ruminal pH (p = 0.08), the concentration of acetic acid (p < 0.05), and the ratio of acetic acid to propionic acid (p < 0.01). Feeding 16.7% oat hay reduced the relative abundance of ruminal Firmicutes, Unidentified-Bacteria, Actinobacteria, Prevotella, NK4A214-group, Olsenella, and Actinobacteriota (p < 0.05); adding CMP increased the relative abundance of ruminal Prevotella, Rikenellaceae-RC9-gut-group, Ruminococcus, NK4A214-group, and Ruminococcus (p < 0.05), and decreased the abundance of Desulfobacterora, Prevotella-7, and Erysipelotricaceae-UCG-002 (p < 0.05). In conclusion, feeding a diet of 16.7% oat hay increased the pelleted starter intake and average daily gain, while slightly reducing the ruminal pH values; adding CMP to the pelleted starter resulted in reduced diarrhea incidence, increased serum antioxidant capacity and immunity, as well as ruminal richness and diversity of microorganisms in dairy calves from 3 to 5 months of age.

Design of High-Precision Parallel AWG Demodulation System.

Here, we present a high-precision demodulation method that supports the arrayed waveguide grating (AWG) system, which includes a 1 × 8 AWG as the primary filter with a 0.5 nm channel spacing and a 1 × 4 AWG as the auxiliary filter with a 1 nm channel spacing. The high precision is achieved through an innovative method of decoupling three channels, involving two adjacent channels of the primary filter and one channel of the secondary auxiliary filter. Simulation results show that the AWGs have a good transmission spectrum with crosstalk below -24.8 dB, non-uniformities below 0.8 dB, insertion loss below -3.7 dB, 3 dB bandwidth of 0.25 nm, and 10 dB bandwidth of 0.43 nm. The interrogation precision can reach 8 pm, with a dynamic range of 0.4 nm, corresponding to a single FBG.

Structure-Based Drug Design of Novel Triaminotriazine Derivatives as Orally Bioavailable IDH2R140Q Inhibitors with High Selectivity and Reduced hERG Inhibitory Activity for the Treatment of Acute Myeloid Leukemia.

Neomorphic IDH2R140Q mutation is commonly found in acute myeloid leukemia (AML), and inhibiting its activity has been validated as an effective treatment for AML. Herein, we report a series of highly potent and selective IDH2R140Q inhibitors. Among them, compound 36 was identified as the most promising inhibitor, with an IC50 value of 29 nM and more than 490-fold selectivity over wild-type IDH2. The compound significantly suppressed D2HG production (IC50 = 10 nM) and induced differentiation in TF-1/IDH2R140Q cells. Furthermore, it showed reasonable pharmacokinetic properties with high bioavailability (F = 90.3%) and an appropriate half-life (T1/2 = 6.4 h). In vivo, oral administration of compound 36 at a dose of 25 mg/kg effectively reduced D2HG levels in the tumor of TF-1/IDH2R140Q xenograft mouse model. Besides, compound 36 displayed little effect on the hERG current. These results suggest that compound 36 has the potential to be an efficacious treatment for AML.