Advances in Antimicrobial Peptide Discovery via Machine Learning and Delivery via Nanotechnology

Antimicrobial peptides (AMPs) have been investigated for their potential use as an alternative to antibiotics due to the increased demand for new antimicrobial agents. AMPs, widely found in nature and obtained from microorganisms, have a broad range of antimicrobial protection, allowing them to be applied in the treatment of infections caused by various pathogenic microorganisms. Since these peptides are primarily cationic, they prefer anionic bacterial membranes due to electrostatic interactions. However, the applications of AMPs are currently limited owing to their hemolytic activity, poor bioavailability, degradation from proteolytic enzymes, and high-cost production. To overcome these limitations, nanotechnology has been used to improve AMP bioavailability, permeation across barriers, and/or protection against degradation. In addition, machine learning has been investigated due to its time-saving and cost-effective algorithms to predict AMPs. There are numerous databases available to train machine learning models. In this review, we focus on nanotechnology approaches for AMP delivery and advances in AMP design via machine learning. The AMP sources, classification, structures, antimicrobial mechanisms, their role in diseases, peptide engineering technologies, currently available databases, and machine learning techniques used to predict AMPs with minimal toxicity are discussed in detail

Effects of Formic or Acetic Acid on the Storage Quality of Mixed Air-Dried Corn Stover and Cabbage Waste, and Microbial Community Analysis

Siliranjem mješovitog otpada od kukuruzovine sušene na zraku i kupusa očuvala se lignocelulozna biomasa koja se može upotrijebiti kao biogorivo. Ispitan je utjecaj dodatka mravlje i octene kiseline u udjelima od 0,3 i 0,6 % (po masi svježe tvari) na kakvoću miješane silaže. Dodatkom mravlje ili octene kiseline silaži prije miješanja povećao se udjel ugljikohidrata topljivih u vodi u usporedbi s negativnom kontrolom, što upućuje na zaključak da se dodatkom kiselina može očuvati veći udjel ugljikohidrata tijekom 170 dana skladištenja. Udjel suhe tvari također se povećao tijekom skladištenja od 90 do 170 dana. Utvrđeno je da je udjel neutralnih i kiselih detergent vlakana, celuloze i holoceluloze (sume celuloze i hemiceluloze) u miješanoj silaži tretiranoj s mravljom ili octenom kiselinom bitno manji nego u negativnoj kontroli, dok su se pH-vrijednost i omjer amonijačnog dušika i ukupnog dušika znatno smanjili. Osim toga, dodatkom tih kiselina bitno je oslabljen intenzitet mliječno-kiselog vrenja, ovisno o omjeru mliječne i octene kiseline, te mliječne kiseline i ukupnih organskih kiselina. Brojnost i relativna zastupljenost bakterijskih vrsta mijenjale su se tijekom siliranja, a dominirale su vrste redova Proteobacteria i Firmicutes. Također je zamijećena promjena u zastupljenosti dominantnih bakterija u biomasi, prije siliranja prevladavale su vrste Lactobacillus i Enterobacter, a nakon siliranja vrste Lactobacillus i Paralactobacillus, dok su bakterije vrste Enterobacter u potpunosti nestale nakon 130 dana skladištenja. Zaključeno je da se dodatkom male doze (0,3 % po masi sježe tvari) octene kiseline bitno poboljšala kvaliteta fermentacije, čime su očuvani organski sastojci silaže.A mixture of air-dried corn stover and cabbage waste was ensiled to preserve lignocellulosic biomass for use as biofuel. Furthermore, the effects of different fresh mass fractions (0.3 and 0.6 %) of formic or acetic acid on the mixed silage quality were evaluated to guarantee its quality. The application of formic or acetic acid prior to mixing the silage led to higher water-soluble carbohydrate fractions than the negative control, indicating that both acids contributed to preservation of water-soluble carbohydrates during storage for 170 days. The dry matter content was also increased after storage from 90 to 170 days. It was found that the content of neutral and acid detergent fibre, cellulose and holocellulose (the sum of cellulose and hemicellulose) in mixed silage treated with formic or acetic acid was significantly lower than that obtained in the negative control. The pH and the ratio of ammoniacal nitrogen to total nitrogen in mixed silage treated with acetic acid also significantly decreased. Furthermore, the addition of formic or acetic acid significantly weakened the fermentation intensity of lactic acid, depending on the ratio of lactic to acetic acid, as well as the ratio of lactic acid to total organic acids. The number of bacterial species and their relative abundance shifted during silage mixing, wherein microbial communities at phylum level mainly consisted of Proteobacteria and Firmicutes. The dominant bacteria were also observed to shift from Lactobacillus and Enterobacter in presilage biomass to Lactobacillus and Paralactobacillus. Specifically, Enterobacter disappeared after 130 days of storage. In conclusion, the addition of a low dose of acetic acid to fresh mass (0.3 %) could effectively improve the fermentation quality and is conducive to the preservation of the organic components

Gut microbial DL-endopeptidase alleviates Crohn's disease via the NOD2 pathway

The pattern-recognition receptor NOD2 senses bacterial muropeptides to regulate host immunity and maintain homeostasis. Loss-of-function mutations in NOD2 are associated with Crohn's disease (CD), but how the variations in microbial factors influence NOD2 signaling and host pathology is elusive. We demonstrate that the Firmicutes peptidoglycan remodeling enzyme, DL-endopeptidase, increased the NOD2 ligand level in the gut and impacted colitis outcomes. Metagenomic analyses of global cohorts (n = 857) revealed that DL-endopeptidase gene abundance decreased globally in CD patients and negatively correlated with colitis. Fecal microbiota from CD patients with low DL-endopeptidase activity predisposed mice to colitis. Administering DL-endopeptidase, but not an active site mutant, alleviated colitis via the NOD2 pathway. Therapeutically restoring NOD2 ligands with a DL-endopeptidase-producing Lactobacillus salivarius strain or mifamurtide, a clinical analog of muramyl dipeptide, exerted potent anti-colitis effects. Our study suggests that the depletion of DL-endopeptidase contributes to CD pathogenesis through NOD2 signaling, providing a therapeutically modifiable target

Mouse Organ-Specific Proteins and Functions

Organ-specific proteins (OSPs) possess great medical potential both in clinics and in biomedical research. Applications of them—such as alanine transaminase, aspartate transaminase, and troponins—in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human populations are well known, yet their effects on OSPs are less addressed. Here, we used mice as a model and implemented a breadth study to examine the panorgan proteome for potential variations in organ specificity in different genetic backgrounds. Using reasonable resources, we generated panorgan proteomes of four in-bred mouse strains. The results revealed a large diversity that was more profound among OSPs than among proteomes overall. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ-specific and are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.&nbsp

Characteristics of Raindrop Size Distribution on the Eastern Slope of the Tibetan Plateau in Summer

Precipitation microphysics over the Tibetan Plateau (TP) remain insufficiently understood, due to the lack of observations and studies. This paper presents a comprehensive investigation of the raindrop size distribution (DSD) for rainfall that happened on the eastern slope of TP in summer. DSD differences between different rain types and under different rain rates are investigated. Confidential empirical relationships between the gamma shape and slope parameters, and between reflectivity and rain rate are proposed. DSD properties in this area are also compared with those in other areas. The results indicate that the stratiform and convective rains contribute to different rain duration and amount, with diverse rainfall macro- and microphysical properties. The rain spectra of two rain types can become broader with higher concentrations as the rain rate increases. DSDs in this area are different to those in other areas. The stratiform DSD is narrower than that in the non-plateau area. The two rain types of this area both have higher number concentrations for 0.437–1.625 mm raindrops than those of the mid-TP. The relationships of shape–slope parameters and reflectivity–rain rate in this area are also different from those in other areas. The rain spectra in this area can produce a larger slope parameter under the same shape parameter than in the mid-TP. The convective rain can produce a smaller rain rate under the same reflectivity. The accuracy proposed reflectivity–rain rate relationship in application to quantitative rainfall estimation is also discussed. The results show that the relationship has an excellent performance when the rain rate exceeds 1 mm h−1

Characteristics of Arctic Summer Inversion and Its Correlation with Extreme Sea Ice Anomalies

Low tropospheric temperature inversion is very common in the Arctic region. Based on the hyperspectral Atmospheric Infrared Sounder (AIRS) profiles from 2002 to 2020, this study provides a comprehensive analysis of the characteristics and anomalies for low tropospheric inversions in the entire Arctic, especially during the summer period. Three types of inversion are classified here, representing the inversions under the clear-sky condition (“clear” inversion), under the cloudy condition with clouds under the inversion layer top (“cloud-I” inversion), and without clouds under the inversion layer top (“cloud-II” inversion). Obvious seasonality is revealed in these three types of inversion, which is stronger in winter than in summer, as per previous studies. We further found that a “summer” peak of inversions occurs in the Arctic, notably in July. Averaged over the study region (60−90° N, 180° W−180° E), the frequencies of “cloud-I” and “cloud-II” inversions peak in July with values of about 22.1% and 34.6%, respectively. Moreover, the three inversion types all display a small “July” peak of inversion strength, ranging from 2.14 to 3.19 K. The result reveals that when the frequency and strength of summer inversions are both with high positive anomalies, there would be a drop in sea ice concentration in September. This implied that the high positive anomalies, both in inversion frequency and strength in summer, might be a predicted signal for the extreme low sea ice event in September. It is also noted that during the extreme low sea ice events in 2007 and 2020, the summer inversion has a strong positive anomaly. However, the summer inversion in 2012, when the sea ice extent also broke the low record, was not extreme as in 2007 and 2020. Further study needs to be supported by follow-up models and observations to evaluate the impact of the inversions on the sea ice

Advances in Chemical Synthesis of Fondaparinux

Fondaparinux (trade name Arixtra) is a safe and efficacious anticoagulant, and it is chemically related to low-molecular-weight heparins such as enoxaparin. Fondaparinux is a synthetic pentasaccharide, and its synthesis is difficult and expensive. The high cost of fondaparinux thwarts its extensive worldwide usage. Over the last two decades, several research groups and pharmaceutical companies have been interested in finding efficient and practical methods for its synthesis. The present review discusses those strategies and their pros and cons in a comparative account

Adaptation of Tree Species in the Greater Khingan Range under Climate Change: Ecological Strategy Differences between <i>Larix gmelinii</i> and <i>Quercus mongolica</i>

Global warming significantly affects forest ecosystems in the Northern Hemisphere’s mid-to-high latitudes, altering tree growth, productivity, and spatial distribution. Additionally, spatial and temporal heterogeneity exists in the responses of different tree species to climate change. This research focuses on two key species in China’s Greater Khingan Range: Larix gmelinii (Rupr.) Kuzen. (Pinaceae) and Quercus mongolica Fisch. ex Ledeb. (Fagaceae). We utilized a Maxent model optimized by the kuenm R package to predict the species’ potential habitats under various future climate scenarios (2050s and 2070s) considering three distinct Shared Socioeconomic Pathways: SSP1-2.6, SSP2-4.5, and SSP5-8.5. We analyzed 313 distribution records and 15 environmental variables and employed geospatial analysis to assess habitat requirements and migration strategies. The Maxent model demonstrated high predictive accuracy, with Area Under the Curve (AUC) values of 0.921 for Quercus mongolica and 0.985 for Larix gmelinii. The high accuracy was achieved by adjusting the regularization multipliers and feature combinations. Key factors influencing the habitat of Larix gmelinii included the mean temperature of the coldest season (BIO11), mean temperature of the warmest season (BIO10), and precipitation of the driest quarter (BIO17). Conversely, Quercus mongolica’s habitat suitability was largely affected by annual mean temperature (BIO1), elevation, and annual precipitation (BIO12). These results indicate divergent adaptive responses to climate change. Quercus mongolica’s habitable area generally increased in all scenarios, especially under SSP5-8.5, whereas Larix gmelinii experienced more complex habitat changes. Both species’ distribution centroids are expected to shift northwestward. Our study provides insights into the divergent responses of coniferous and broadleaf species in the Greater Khingan Range to climate change, contributing scientific information vital to conserving and managing the area’s forest ecosystems

Formation of inclusion complex of enrofloxacin with 2-hydroxypropyl-β-cyclodextrin

Enrofloxacin, a third-generation fluoroquinolone, is a broad-spectrum antimicrobial drug against a lot of veterinary bacterial diseases. However, bactericidal activity of enrofloxacin is concentration-dependent and its poor aqueous solubility and bitter taste limit its development and application. Meanwhile, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used cyclodextrin analog, is a safe and an effective drug carrier. It forms inclusion complexes with its drug substrates and improves their physiochemical and pharmacokinetic properties. Enrofloxacin was also found to form a stable inclusion complex with HP-β-CD and different research groups have shown improved solubility for enrofloxacin by 32.5%, 9.25 and 165-fold. Our own efforts in this direction resulted in manifold improvement (916-fold) in its solubility compared to the previous studies. It was further shown that pharmaceutical properties, absorption and bioavailability, of enrofloxacin have also been significantly improved by complexation with HP-β-CD