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The crude protein (CP) content is an important determining factor for the quality of alfalfa, and its accurate and rapid evaluation is a challenge for the industry. A model was developed by combining Fourier transform infrared spectroscopy (FTIS) and chemometric analysis. Fourier spectra were collected in the range of 4000~400 cm−1. Adaptive iteratively reweighted penalized least squares (airPLS) and Savitzky–Golay (SG) were used for preprocessing the spectral data; competitive adaptive reweighted sampling (CARS) and the characteristic peaks of CP functional groups and moieties were used for feature selection; partial least squares regression (PLSR) and random forest regression (RFR) were used for quantitative prediction modelling. By comparing the combined prediction results of CP content, the predictive performance of airPLST-cars-PLSR-CV was the best, with an R P 2 of 0.99 and an RMSEP of 0.053, which is suitable for establishing a small-sample prediction model. The research results show that the combination of the PLSR model can achieve an accurate prediction of the crude protein content of alfalfa forage, which can provide a reliable and effective new detection method for the crude protein content of alfalfa forage. [ABSTRACT FROM AUTHOR]

The Tianshan range, a Paleozoic orogenic belt in Central Asia, has undergone multiple phases of tectonic activities characterized by the N–S compression after the early Mesozoic, including the far‐field effects of the Cenozoic Indian–Asian collision. However, there are limited reports on the tectonic deformation and initiation of Triassic intracontinental deformation in the Tianshan range. Understanding this structural context is crucial for interpreting the early intracontinental deformation history of the Eurasian continent during the early Mesozoic. Growth strata and syn‐tectonic sediments provide a rich source of information on tectonic activities and have been extensively used in the studies of orogenic belts. Based on detail fieldwork conducted in this study, the middle–late Triassic Kelamayi Formation of the northern Kuqa Depression in the southern Tianshan fold‐thrust belt has been identified as the typical syn‐tectonic growth strata. The youngest detrital zircon component in two lithic sandstone samples from the bottom and top of the Kelamayi growth strata yielded U‐Pb ages of 223.4 ± 3.1 and 215.5 ± 2.9 Ma, respectively, indicating that the maximum depositional age of the bottom and top of the Kelamayi growth strata is 226–220 and 218–212 Ma. The geochronological distribution of detrital samples from the Early–Middle Triassic and Late Triassic revealed abrupt changes, suggesting a new source supply resulting from tectonic activation in the Tianshan range. The coupling relationship between the syn‐tectonic sedimentation of the Kelamayi Formation and the South Tianshan fold‐thrust system provides robust evidence that the Triassic intracontinental deformation of the South Tianshan range began at approximately 226–220 Ma (during the Late Triassic) and ended at approximately 218–212 Ma. These findings provide crucial constraints for understanding the intraplate deformation in the Tianshan range during the Triassic. [ABSTRACT FROM AUTHOR]

We examined formulating a new antifungal agent, posaconazole (POS) and its derivatives, with different molecular vehicles. Several combinations of drug and carrier molecules were synthesized, and their antifungal activities were evaluated against Aspergillus fumigatus. Posaconazole and four of its derivatives were conjugated to either generation 5 (G5) dendrimers or partially modified G5 dendrimers. The in vitro antifungal activities of these compounds suggest that conjugates with specific chemical linkages showed better fungistatic activity than direct conjugates to POS. In particular, a polyethylene glycol (PEG)-imidazole modified G5 dendrimer demonstrated improved antifungal efficacy relative to the parent G5 molecule. Further studies were then conducted with POS derived molecules coupled to PEG-imidazole modified G5 dendrimers to achieve a highly soluble and active conjugate of POS. This conjugated macromolecule averaged 23 POS molecules per G5 and had a high solubility with 50 mg/mL, which improved the molar solubility of POS from less than 0.03 mg/mL to as high as 16 mg/mL in water. The primary release profile of the drug in human plasma was extended to over 72 h, which is reflected in the in vitro inhibition of A. fumigatus growth of over 96 h. These POS–polymer conjugates appear to be novel and efficient antifungal agents.

The hedgehog (HH) signaling pathway is one of the key pathways that is indispensable for many developmental processes and postnatal tissue homeostasis. Dysregulated HH signaling could lead to developmental disorders and tumorigenesis in a variety of tissues via inherited or sporadic mutation, gene overexpression, and crosstalk with other signaling pathways. Recently, accumulating evidence has shown that HH signaling is targeted by viruses to facilitate viral transcription, immune evasion, and uncontrolled growth, leading to effective viral replication and pathogenesis. In this study, we will summarize recent advances in functional interaction between HH signaling and different types of viruses, particularly focusing on the pathological role of HH signaling in viral infections and related diseases.

Abstract Background Targeted contrast nanoparticles for breast tumor imaging facilitates early detection and improves treatment efficacy of breast cancer. This manuscript reports the development of an epidermal growth factor receptor-2 (HER-2) specific, bi-modal, dendrimer conjugate to enhance computed tomography (CT) and magnetic resonance imaging (MRI) of HER-2-positive breast cancer. This material employs generation 5 poly(amidoamine) dendrimers, encapsulated gold nanoparticles, chelated gadolinium, and anti-human HER-2 antibody to produce the nanoparticle contrast agent. Results Testing in two mouse tumor models confirms this contrast agent’s ability to image HER-2 positive tumors. Intravenous injection of this nanoparticle in mice bearing HER-2 positive mammary tumors significantly enhances MRI signal intensity by ~ 20% and improves CT resolution and contrast by two-fold. Results by flow cytometry and confocal microscopy validate the specific targeting of the conjugate and its internalization in human HER-2 positive cells. Conclusion These results demonstrate that this nanoparticle conjugate can efficiently target and image HER-2 positive tumors in vivo and provide a basis for the development of this diagnostic tool for early detection, metastatic assessment and therapeutic monitoring of HER-2 positive cancers.

A comprehensive investigation of elastic and inelastic electron scattering from molecular pyridine is reported using the ab initio R-matrix method with the static exchange plus polarization and close-coupling approximations for incident energies up to 10 eV. The two well-known low-lying 1 2B1 and 1 2A2 shape resonances as well as a 2 2B1 mixed-character resonance compare well with the theoretical and experimental results. We also detect five core-excited resonances (1 2A1, 1 2B2, 3 2B1, 2 2A2, and 4 2B1), which lie above the first electronic excitation threshold. The total elastic cross sections and momentum transfer cross sections agree reasonably with previous reference data. Comparisons of the differential elastic cross sections of pyridine with those measured for benzene, pyrazine, and pyrimidine show remarkable agreement at scattering angles above 40° but behave differently for forward scattering below 40° below 6 eV, due to the dominant effect of the permanent dipole moment on the differential cross section in the low energy region with narrow scattering angles. Inelastic electronic excitation cross sections are presented, showing the influence of core-excited resonances below the ionization threshold for the first time. [ABSTRACT FROM AUTHOR]

In order to investigate the fracturing behavior of rocks under the influence of plasma shock waves, high-voltage pulsed breakdown experiments on red sandstone were conducted at various discharge distances. The crack propagation process of red sandstone specimens was observed by an ultra-high-speed camera, and the influence of discharge distance on the surface crack density of red sandstone under plasma shock wave was discussed. Subsequently, a finite element model, in line with the experimental conditions, was developed using the numerical simulation software LS-DYNA, the simulation and experimental results were compared, and the experimental process was reproduced. The results indicated that under the action of the plasma shock wave, the damage on the two surfaces perpendicular to the discharge channel is mainly radial cracks, while the damage on the four sides parallel to the discharge channel is mainly transverse cracks. As the discharge distance increased, the crack density on the surface of the specimens gradually increased. The numerical simulation results were used to analyze the internal fracturing process of the specimens and the attenuation of stress waves. It was found that as the discharge distance increased, the effective stress generated within the red sandstone samples by the plasma shock waves exhibited an exponential decay, with the peak effective stress near the free surface tending towards stability. [ABSTRACT FROM AUTHOR]

ABSTRACT Infections triggered by pathogenic fungi cause a serious threat to the public health care system. In particular, an increase of antifungal drug-resistant fungi has resulted in difficulty in treatment. A limited variety of antifungal drugs available to treat patients has left us in a situation where we need to develop new therapeutic approaches that are less prone to development of resistance by pathogenic fungi. In this study, we demonstrate the efficacy of the nanoemulsion NB-201, which utilizes the surfactant benzalkonium chloride, against human-pathogenic fungi. We found that NB-201 exhibited in vitro activity against Candida albicans, including both planktonic growth and biofilms. Furthermore, treatments with NB-201 significantly reduced the fungal burden at the infection site and presented an enhanced healing process after subcutaneous infections by multidrug-resistant C. albicans in a murine host system. NB-201 also exhibited in vitro growth inhibition activity against other fungal pathogens, including Cryptococcus spp., Aspergillus fumigatus, and Mucorales. Due to the nature of the activity of this nanoemulsion, there is a minimized chance of drug resistance developing, presenting a novel treatment to control fungal wound or skin infections. IMPORTANCE Advances in medicine have resulted in the discovery and implementation of treatments for human disease. While these recent advances have been beneficial, procedures such as solid-organ transplants and cancer treatments have left many patients in an immunocompromised state. Furthermore, the emergence of immunocompromising diseases such as HIV/AIDS or other immunosuppressive medical conditions have opened an opportunity for fungal infections to afflict patients globally. The development of drug resistance in human-pathogenic fungi and the limited array of antifungal drugs has left us in a scenario where we need to develop new therapeutic approaches to treat fungal infections that are less prone to the development of resistance by pathogenic fungi. The significance of our work lies in utilizing a novel nanoemulsion formulation to treat topical fungal infections while minimizing risks of drug resistance development.

Aims: To verify the hypothesis that an enriched environment (EE) alleviates sleep deprivation‐induced fear memory impairment by modulating the basal forebrain (BF) PIEZO1/calpain/autophagy pathway. Methods: Eight‐week‐old male mice were housed in a closed, isolated environment (CE) or an EE, before 6‐h total sleep deprivation. Changes in fear memory after sleep deprivation were observed using an inhibitory avoidance test. Alterations in BF PIEZO1/calpain/autophagy signaling were detected. The PIEZO1 agonist Yoda1 or inhibitor GsMTx4, the calpain inhibitor PD151746, and the autophagy inducer rapamycin or inhibitor 3‐MA were injected into the bilateral BF to investigate the pathways involved in the memory‐maintaining role of EE in sleep‐deprived mice. Results: Mice housed in EE performed better than CE mice in short‐ and long‐term fear memory tests after sleep deprivation. Sleep deprivation resulted in increased PIEZO1 expression, full‐length tropomyosin receptor kinase B (TrkB‐FL) degradation, and autophagy, as reflected by increased LC3 II/I ratio, enhanced p62 degradation, increased TFEB expression and nuclear translocation, and decreased TFEB phosphorylation. These molecular changes were partially reversed by EE treatment. Microinjection of Yoda1 or rapamycin into the bilateral basal forebrain induced excessive autophagy and eliminated the cognition‐protective effects of EE. Bilateral basal forebrain microinjection of GsMTx4, PD151746, or 3‐MA mimicked the cognitive protective and autophagy inhibitory effects of EE in sleep‐deprived mice. Conclusions: EE combats sleep deprivation‐induced fear memory impairments by inhibiting the BF PIEZO1/calpain/autophagy pathway. [ABSTRACT FROM AUTHOR]

As antimicrobial resistance has been increasing, new antimicrobial agents are desperately needed. Azalomycin F, a natural polyhydroxy macrolide, presents remarkable antimicrobial activities. To investigate its pharmacokinetic characteristics in rats, the concentrations of azalomycin F contained in biological samples, in vitro, were determined using a validated high-performance liquid chromatography–ultraviolet (HPLC-UV) method, and, in vivo, samples were assayed by an ultra-high performance liquid chromatography–tandem mass spectrometric (UPLC–MS/MS) method. Based on these methods, the pharmacokinetics of azalomycin F were first investigated. Its plasma concentration-time courses and pharmacokinetic parameters in rats were obtained by a non-compartment model for oral (26.4 mg/kg) and intravenous (2.2 mg/kg) administrations. The results indicate that the oral absolute bioavailability of azalomycin F is very low (2.39 ± 1.28%). From combinational analyses of these pharmacokinetic parameters, and of the results of the in-vitro absorption and metabolism experiments, we conclude that azalomycin F is absorbed relatively slowly and with difficulty by the intestinal tract, and subsequently can be rapidly distributed into the tissues and/or intracellular f of rats. Azalomycin F is stable in plasma, whole blood, and the liver, and presents plasma protein binding ratios of more than 90%. Moreover, one of the major elimination routes of azalomycin F is its excretion through bile and feces. Together, the above indicate that azalomycin F is suitable for administration by intravenous injection when used for systemic diseases, while, by oral administration, it can be used in the treatment of diseases of the gastrointestinal tract.

Viruses deploy multiple strategies to suppress the host innate immune response to facilitate viral replication and pathogenesis. Typical G3BP1+ stress granules (SGs) are usually formed in host cells after virus infection to restrain viral translation and to stimulate innate immunity. Thus, viruses have evolved various mechanisms to inhibit SGs or to repurpose SG components such as G3BP1. Previous studies showed that severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) infection inhibited host immunity during the early stage of COVID-19. However, the precise mechanism is not yet well understood. Here we showed that the SARS-CoV-2 nucleocapsid (SARS2-N) protein suppressed the doublestranded RNA (dsRNA)-induced innate immune response, concomitant with inhibition of SGs and the induction of atypical SARS2-N+/G3BP1+ foci (N+foci). The SARS2-N protein--induced formation of N+foci was dependent on the ability of its ITFG motif to hijack G3BP1, which contributed to suppress the innate immune response. Importantly, SARS2-N protein facilitated viral replication by inducing the formation of N+foci. Viral mutations within SARS2-N protein that impair the formation of N+foci are associated with the inability of the SARS2-N protein to suppress the immune response. Taken together, our study has revealed a novel mechanism by which SARS-CoV-2 suppresses the innate immune response via induction of atypical N+foci. We think that this is a critical strategy for viral pathogenesis and has potential therapeutic implications. [ABSTRACT FROM AUTHOR]