Design of Inhibitors Targeting Chitin-Degrading Enzymes by Bioisostere Substitutions and Scaffold Hopping for Selective Control of Ostrinia furnacalis.

Chitin-degrading enzymes are critical components in regulating the molting process of the Asian corn borer and serve as potential targets for controlling this destructive pest of maize. Here, we used a scaffold-hopping strategy to design a series of efficient naphthylimide insecticides. Among them, compound 8c exhibited potent inhibition of chitinase from OfChi-h and OfChtI at low nanomolar concentrations (IC50 = 1.51 and 9.21 nM, respectively). Molecular docking simulations suggested that 8c binds to chitinase by mimicking the interaction of chitin oligosaccharide substrates with chitinase. At low ppm concentrations, compound 8c performed comparably to commercial insecticides in controlling the highly destructive plant pest, the Asian corn borer. Tests on a wide range of nontarget organisms indicate that compound 8c has very low toxicity. In addition, the effect of inhibitor treatment on the expression of genes associated with the Asian corn borer chitin-degrading enzymes was further investigated by quantitative real-time polymerase chain reaction. In conclusion, our study highlights the potential of 8c as a novel chitinase-targeting insecticide for effective control of the Asian corn borer, providing a promising solution in the quest for sustainable pest management.

Polyethylene terephthalate (PET)-degrading bacteria in the pelagic deep-sea sediments of the Pacific Ocean.

Polyethylene terephthalate (PET) plastic pollution is widely found in deep-sea sediments. Despite being an international environmental issue, it remains unclear whether PET can be degraded through bioremediation in the deep sea. Pelagic sediments obtained from 19 sites across a wide geographic range in the Pacific Ocean were used to screen for bacteria with PET degrading potential. Bacterial consortia that could grow on PET as the sole carbon and energy source were found in 10 of the 19 sites. These bacterial consortia showed PET removal rate of 1.8%-16.2% within two months, which was further confirmed by the decrease of carbonyl and aliphatic hydrocarbon groups using attenuated total reflectance-Fourier-transform infrared analysis (ATR-FTIR). Analysis of microbial diversity revealed that Alcanivorax and Pseudomonas were predominant in all 10 PET degrading consortia. Meanwhile, Thalassospira, Nitratireductor, Nocardioides, Muricauda, and Owenweeksia were also found to possess PET degradation potential. Metabolomic analysis showed that Alcanivorax sp. A02-7 and Pseudomonas sp. A09-2 could turn PET into mono-(2-hydroxyethyl) terephthalate (MHET) even in situ stimulation (40 MPa, 10 °C) conditions. These findings widen the currently knowledge of deep-sea PET biodegrading process with bacteria isolates and degrading mechanisms, and indicating that the marine environment is a source of biotechnologically promising bacterial isolates and enzymes.

The levels of IL1RN is a factor influencing the onset of rheumatoid arthritis in non-alcoholic fatty liver disease.

With the improvement of global dietary conditions, non-alcoholic fatty liver disease (NAFLD) has gradually become prevalent. As the number of NAFLD patients increases, the coexistence of diseases associated with it has come into focus. In this study, based on immune phenotypes, intercellular communication activities, and clinical manifestations of NAFLD patients, IL1RN was identified as a central pro-inflammatory factor. Subsequently, potential downstream biological pathways of IL1RN in liver tissues and various cell types were enriched to describe its functions. Transcription factors Nfkb1, Jun, and Sp1, significantly associated with these functions, were also enriched. Functional studies of IL1RN suggest its potential to trigger autoimmune diseases. Given this, Mendelian randomization analysis was used to explore the causal relationship between NAFLD and various autoimmune diseases, with IL1RN considered as an intermediary introduced into Mendelian randomization studies. The results indicate that IL1RN and its partially related proteins play a certain mediating role in the process of NAFLD inducing rheumatoid arthritis (RA). Finally, additional research results suggest that intrahepatic ALT levels may influence IL1RN levels, possibly through amino acid metabolism.

Intermolecular interactions in mixed dye systems and the effects on dye wastewater treatment processes.

Dye wastewater discharge is a critical concern across textiles, paper, cosmetics, and other industries. This study explores the impact of dye-dye interactions on chemical coagulation and ultrafiltration process. Using basic and reactive dyes, representing cationic and anionic compounds, the intricate interplay between these dyes was examined through spectroscopic analysis. Remarkably, interactions between dyes of opposite charges exhibited significant effects on both techniques. Electrostatic attractions played a key role. Positive coagulant hydrolysates selectively attracted negative dyes, while negatively charged membranes effectively captured positive dyes. Combining dyes with opposite charges resulted in enhanced removal efficiency, addressing challenging dyes collectively. This discovery offers a novel approach to improving dye removal, utilizing opposite-charged dye mixtures can tackle stubborn dyes unmanageable by conventional methods.

Progress in the treatment of drug-loaded nanomaterials in renal cell carcinoma.

Renal cell carcinoma (RCC) is a common urinary tract tumor that arises from the highly heterogeneous epithelium of the renal tubules. The incidence of kidney cancer is second only to the incidence of bladder cancer, and has shown an upward trend over time. Although surgery is the preferred treatment for localized RCC, treatment decisions should be customized to individual patients considering their overall health status and the risk of developing or worsening chronic kidney disease postoperatively. Anticancer drugs are preferred to prevent perioperative and long-term postoperative complications; however, resistance to chemotherapy remains a considerable problem during the treatment process. To overcome this challenge, nanocarriers have emerged as a promising strategy for targeted drug delivery for cancer treatment. Nanocarriers can transport anticancer agents, achieving several-fold higher cytotoxic concentrations in tumors and minimizing toxicity to the remaining parts of the body. This article reviews the use of nanomaterials, such as liposomes, polymeric nanoparticles, nanocomposites, carbon nanomaterials, nanobubbles, nanomicelles, and mesoporous silica nanoparticles, for RCC treatment, and discusses their advantages and disadvantages.

Efficiently Removing Heavy Metals from High-Salinity Wastewater via Ionic Liquid-Based Aqueous Biphasic Systems.

For the separation of metal ions, ionic liquid-based aqueous biphasic systems (IL-ABSs) offer a promising alternative to solvent extraction. However, the incorporation of an extensive quantity of inorganic salts restricts their practical application. Because heavy metal wastewater often contains high concentrations of inorganic salts, it offers good prospects for the application of IL-ABSs in the separation of heavy metals. In this work, an IL-ABS was formed by tributyltetradecylphosphonium chloride ([P44414]Cl), and simulated high-salinity wastewater (NaCl and Na2SO4 as the main inorganic salts) was used for the separation of heavy metals. The phase diagram results indicated that the formation of a two-phase system required a relatively high salt concentration. The extraction process followed the mechanism of anion exchange; thus, heavy metals such as zinc and cadmium that formed complexes with chloride ions could be effectively extracted (extraction rate >99.5%) with a very fast rate (extraction time <1 min) at a wide pH range (pH = 2-7). After extraction, the metals could be stripped well (stripping rate >99.5%) after contact with the NaOH solution. This research provided a new approach for treating heavy metals in high-salinity effluents, which has the advantages of IL-ABS and avoids the disadvantages of adding large amounts of inorganic salts at the same time.

Novel mechanisms for the synthesis of important secondary metabolites in Ginkgo biloba seed revealed by multi-omics data.

Although the detailed biosynthetic mechanism is still unclear, the unique secondary metabolites of Ginkgo biloba, including ginkgolic acids (GAs) and terpene trilactones, have attracted increasing attention for their potent medicinal, physiological and biochemical properties. In particular, GAs have shown great potential in the fields of antibacterial and insecticidal activities, making it urgent to elucidate their biosynthetic mechanism. In this study, we systematically revealed the landscape of metabolic-transcriptional regulation across continuous growth stages of G. biloba seeds (GBS) based on multi-omics mining and experimental verification, and successfully identified all major types of GAs and terpene trilactones along with more than a thousand kinds of other metabolites. The phenological changes and the essential gene families associated with these unique metabolites were analyzed in detail, and several potential regulatory factors were successfully identified based on co-expression association analysis. In addition, we unexpectedly found the close relationship between large introns and the biosynthesis of these secondary metabolites. These genes with large introns related to the synthesis of secondary metabolites showed higher gene expression and expression stability in different tissues or growth stages. Our results may provide a new perspective for the study of the regulatory mechanism of these unique secondary metabolites in GBS.

Application of Natural Bioresources to Sustainable Agriculture: A C-Glycoside Insecticide Based on N-Acetyl-glucosamine for Regulating Insect Molting of Ostrinia furnacalis.

In order to increase the application of natural bioresources in drug discovery and development, a study on N-acetyl-glucosamine (GlcNAc) derivatives of chitin as green pesticides was necessary. In this study, we designed and synthesized a series of novel C-glycoside naphthalimides using GlcNAc as a starting material. Compound 10l showed high inhibitory activity against OfHex1 (IC50 = 1.77 µM), with a nearly 30-fold increase in activity over our previously reported C-glycoside CAUZL-A (IC50 = 47.47 µM). By observing the morphology of the Ostrinia furnacalis, we found that the synthesized compounds significantly inhibited the molting process. In addition, we further explored the morphological changes of the inhibitor-treated O. furnacalis cuticle using scanning electron microscopy. This is the first study to validate the insecticidal mechanism of OfHex1 inhibitors at the microscale level. Several compounds also exhibited excellent larvicidal activity against Plutella xylostella. Moreover, the toxicity measurements and predictions indicated that the C-glycoside naphthalimides have little effect on the natural enemy Trichogramma ostriniae and rats. Together, our results highlight an approach for the design of green pesticides, taking advantage of natural bioresources to control pests in agriculture.

Ejecta from the DART-produced active asteroid Dimorphos.

Some active asteroids have been proposed to be formed as a result of impact events1. Because active asteroids are generally discovered by chance only after their tails have fully formed, the process of how impact ejecta evolve into a tail has, to our knowledge, not been directly observed. The Double Asteroid Redirection Test (DART) mission of NASA2, in addition to having successfully changed the orbital period of Dimorphos3, demonstrated the activation process of an asteroid resulting from an impact under precisely known conditions. Here we report the observations of the DART impact ejecta with the Hubble Space Telescope from impact time T + 15 min to T + 18.5 days at spatial resolutions of around 2.1 km per pixel. Our observations reveal the complex evolution of the ejecta, which are first dominated by the gravitational interaction between the Didymos binary system and the ejected dust and subsequently by solar radiation pressure. The lowest-speed ejecta dispersed through a sustained tail that had a consistent morphology with previously observed asteroid tails thought to be produced by an impact4,5. The evolution of the ejecta after the controlled impact experiment of DART thus provides a framework for understanding the fundamental mechanisms that act on asteroids disrupted by a natural impact1,6.

Momentum transfer from the DART mission kinetic impact on asteroid Dimorphos.

The NASA Double Asteroid Redirection Test (DART) mission performed a kinetic impact on asteroid Dimorphos, the satellite of the binary asteroid (65803) Didymos, at 23:14 UTC on 26 September 2022 as a planetary defence test1. DART was the first hypervelocity impact experiment on an asteroid at size and velocity scales relevant to planetary defence, intended to validate kinetic impact as a means of asteroid deflection. Here we report a determination of the momentum transferred to an asteroid by kinetic impact. On the basis of the change in the binary orbit period2, we find an instantaneous reduction in Dimorphos's along-track orbital velocity component of 2.70 ± 0.10 mm s-1, indicating enhanced momentum transfer due to recoil from ejecta streams produced by the impact3,4. For a Dimorphos bulk density range of 1,500 to 3,300 kg m-3, we find that the expected value of the momentum enhancement factor, ß, ranges between 2.2 and 4.9, depending on the mass of Dimorphos. If Dimorphos and Didymos are assumed to have equal densities of 2,400 kg m-3, [Formula: see text]. These ß values indicate that substantially more momentum was transferred to Dimorphos from the escaping impact ejecta than was incident with DART. Therefore, the DART kinetic impact was highly effective in deflecting the asteroid Dimorphos.

Self-Aware Artificial Coiled Yarn Muscles with Enhanced Electrical Conductivity and Durability via a Two-Step Process.

Muscles are capable of modulating the body and adapting to environmental changes with a highly integrated sensing and actuation. Inspired by biological muscles, coiled/twisted fibers are adopted that can convert volume expansion into axial contraction and offer the advantages of flexibility and light weight. However, the sensing-actuation integrated fish line/yarn-based artificial muscles are still barely reported due to the poor actuation-sensing interface with off-the-shelf fibers. We report herein artificial coiled yarn muscles with self-sensing and actuation functions using the commercially available yarns. Via a two-step process, the artificial coiled yarn muscles are proved to obtain enhanced electrical conductivity and durability, which facilitates the long-term application in human-robot interfaces. The resistivity is successfully reduced from 172.39 Ω·cm (first step) to 1.27 Ω·cm (second step). The multimode sense of stretch strain, pressure, and actuation-sensing are analyzed and proved to have good linearity, stability and durability. The muscles could achieve a sensitivity (gauge factor, GF) of the contraction strain perception up to 1.5. We further demonstrate this self-aware artificial coiled yarn muscles could empower non-active objects with actuation and real-time monitoring capabilities without causing damage to the objects. Overall, this work provides a facile and versatile tool in improving the actuation-sensing performances of the artificial coiled yarn muscles and has the potential in building smart and interactive soft actuation systems.

Nanoparticle-mediated therapeutic management in cholangiocarcinoma drug targeting: Current progress and future prospects.

Patients with cholangiocarcinoma (CCA) often have an unfavorable prognosis because of its insidious nature, low resectability rate, and poor response to anticancer drugs and radiotherapy, which makes early detection and treatment difficult. At present, CCA has a five-year overall survival rate (OS) of only 5%, despite advances in therapies. New an increasing number of evidence suggests that nanoplatforms may play a crucial role in enhancing the pharmacological effects and in reducing both short- and long-term side effects of cancer treatment. This document reviews the advantages and shortcomings of nanoparticles such as liposomes, polymeric nanoparticle，inorganic nanoparticle, nano-metals and nano-alloys, carbon dots, nano-micelles, dendrimer, nano-capsule, bio-Nanomaterials in the diagnosis and treatment of CCA and discuss the current challenges in of nanoplatforms for CCA.

Lignin-oxidizing and xylan-hydrolyzing Vibrio involved in the mineralization of plant detritus in the continental slope.

A large amount of terrigenous organic matter (TOM) is constantly transported to the deep sea. However, relatively little is known about the microbial mineralization of TOM therein. Our recent in situ enrichment experiments revealed that Vibrio is especially enriched as one of the predominant taxa in the cultures amended with natural plant materials in the deep sea. Yet their role in the mineralization of plant-derived TOM in the deep sea remains largely unknown. Here we isolated Vibrio strains representing dominant members of the enrichments and verified their potential to degrade lignin and xylan. The isolated strains were closely related to Vibrio harveyi, V. alginolyticus, V. diabolicus, and V. parahaemolyticus. Extracellular enzyme assays, and genome and transcriptome analyses revealed diverse peroxidases, including lignin peroxidase (LiP), catalase-peroxidase (KatG), and decolorizing peroxidase (DyP), which played an important role in the depolymerization and oxidation of lignin. Superoxide dismutase was found to likely promote lignin oxidation by supplying H2O2 to LiP, DyP, and KatG. Interestingly, these deep-sea Vibrio strains could oxidize lignin and hydrolyze xylan not only through aerobic pathway, but also through anaerobic pathway. Genome analysis revealed multiple anaerobic respiratory mechanisms, including the reductions of nitrate, arsenate, tetrathionate, and dimethyl sulfoxide. The strains showed the potential to anaerobically reduce sulfite and metal oxides of iron and manganese, in contrast the non-deep-sea Vibrio strains were not retrieved of genes involved in reduction of metal oxides. This is the first report about the lignin oxidation mechanisms in Vibrio and their role in TOM mineralization in anoxic and oxic environments of the marginal sea.

Frequent Occurrence and Metabolic Versatility of Marinifilaceae Bacteria as Key Players in Organic Matter Mineralization in Global Deep Seas.

Transfer of animal and plant detritus of both terrestrial and marine origins to the deep sea occurs on a global scale. Microorganisms play an important role in mineralizing them therein, but these are yet to be identified in situ. To observe key bacteria involved, we conducted long-term in situ incubation and found that members of the family Marinifilaceae (MF) occurred as some of the most predominant bacteria thriving on the new inputs of plant and animal biomasses in the deep sea in both marginal and oceanic areas. This taxon is diverse and ubiquitous in marine environments. A total of 11 MAGs belonging to MF were retrieved from metagenomic data and diverged into four subgroups in the phylogenomic tree. Based on metagenomic and metatranscriptomic analyses, we described the metabolic features and in situ metabolizing activities of different subgroups. The MF-2 subgroup, which dominates plant detritus-enriched cultures, specializes in polysaccharide degradation and lignin oxidation and has high transcriptional activities of related genes in situ. Intriguingly, members of this subgroup encode a nitrogen fixation pathway to compensate for the shortage of nitrogen sources inside the plant detritus. In contrast, other subgroups dominating the animal tissue-supported microbiomes are distinguished from MF-2 with regard to carbon and nitrogen metabolism and exhibit high transcriptional activity for proteolysis in situ. Despite these metabolic divergences of MF lineages, they show high in situ transcriptional activities for organic fermentation and anaerobic respiration (reductions of metal and/or dimethyl sulfoxide). These results highlight the role of previously unrecognized Marinifilaceae bacteria in organic matter mineralization in marine environments by coupling carbon and nitrogen cycling with metal and sulfur. IMPORTANCE Microbial mineralization of organic matter has a significant impact on the global biogeochemical cycle. This report confirms the role of Marinifilaceae in organic degradation in the oceans, with a contribution to ocean carbon cycling that has previously been underestimated. It was the dominant taxon thriving on plant and animal biomasses in our in situ incubator, as well as in whale falls and wood falls. At least 9 subgroups were revealed, and they were widely distributed in oceans globally but predominant in organic-matter-rich environments, with an average relative abundance of 8.3%. Different subgroups display a preference for the degradation of different macromolecules (polysaccharides, lignin, and protein) and adapt to their environments via special metabolic mechanisms.

Current Strategies and Potential Prospects for Nanoparticle-Mediated Treatment of Diabetic Nephropathy.

Diabetic nephropathy (DN), a severe microvascular complication of diabetes mellitus (DM), is the most common form of chronic kidney disease (CKD) and a leading cause of renal failure in end-stage renal disease. No currently available treatment can achieve complete cure. Traditional treatments have many limitations, such as painful subcutaneous insulin injections, nephrotoxicity and hepatotoxicity with oral medication, and poor patient compliance with continual medication intake. Given the known drawbacks, recent research has suggested that nanoparticle-based drug delivery platforms as therapeutics may provide a promising strategy for treating debilitating diseases such as DN in the future. This administration method provides multiple advantages, such as delivering the loaded drug to the precise target of action and enabling early prevention of CKD progression. This article discusses the development of the main currently used nanoplatforms, such as liposomes, polymeric NPs, and inorganic NPs, as well as the prospects and drawbacks of nanoplatform application in the treatment of CKD.

GAUSS - genesis of asteroids and evolution of the solar system: A sample return mission to Ceres.

The goal of Project GAUSS (Genesis of Asteroids and evolUtion of the Solar System) is to return samples from the dwarf planet Ceres. Ceres is the most accessible candidate of ocean worlds and the largest reservoir of water in the inner Solar System. It shows active volcanism and hydrothermal activities in recent history. Recent evidence for the existence of a subsurface ocean on Ceres and the complex geochemistry suggest past habitability and even the potential for ongoing habitability. GAUSS will return samples from Ceres with the aim of answering the following top-level scientific questions: What is the origin of Ceres and what does this imply for the origin of water and other volatiles in the inner Solar System?What are the physical properties and internal structure of Ceres? What do they tell us about the evolutionary and aqueous alteration history of dwarf planets?What are the astrobiological implications of Ceres? Is it still habitable today?What are the mineralogical connections between Ceres and our current collections of carbonaceous meteorites?

Hypertension is associated with osteoporosis: a case-control study in Chinese postmenopausal women.

BACKGROUND: Osteoporosis and cardiovascular disease (CVD) are age-related diseases. It is reported that patients with CVD have a higher risk of bone loss. This retrospective study sought to reveal the association between osteoporosis and CVD in Chinese women. Although epidemiological evidence has indicated a relationship between the two, clinical data in southeast China are lacking. METHODS: In total, 2873 participants completed the baseline survey from January 2007 to October 2019, and 2039 were included in this retrospective study. We divided all subjects into an osteoporosis group and a non-osteoporosis group based on their bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA) was used to examine BMD. The general information came from the questionnaire survey. Cardiovascular diseases were defined by asking participants at the first visit and checking relevant medical records if they had suffered from hypertension, coronary heart disease, or cerebral infarction. RESULTS: According to the criterion, the osteoporosis group had 678 subjects, and the non-osteoporosis group had 1361 subjects. Subjects in the osteoporosis group had a significantly higher prevalence of hypertension and coronary heart disease. Besides, the proportion of subjects who drank tea and drank milk were relatively higher in the osteoporosis group. The odds ratio (OR) for suffering from osteoporosis was high if the patients had hypertension. CONCLUSIONS: This study indicated that Chinese postmenopausal women with osteoporosis had a higher prevalence of hypertension. Hypertension was significantly associated with osteoporosis.

Total hip arthroplasty for tuberculosis: a case series.

BACKGROUND: The purpose of this study is to investigate the optimal surgical options for different kinds of advanced hip tuberculosis, which are still controversial. METHODS: We reviewed seven advanced hip tuberculosis patients received operations from November 2014 to September 2018. All patients received anti-tubercular chemotherapy at least 2 weeks preoperatively and twelve months postoperatively. One active case with sinus tract of seven patients underwent three-stage operations including two debridements/cement spacer implantations and one total hip arthroplasty, while the other six cases received one = stage arthroplasty surgery. All patients are followed up based on Harris score, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and X-ray. RESULTS: The mean follow-up time was 41.6 months, while no reactivation was detected. The average Harris score increased from 40.0 preoperatively to 89.4 at the final follow-up. ESR of 3 active hip tubercular cases decreased from 143.7 mm/L at diagnosis time to 6.7 mm/L at the final follow-up. CRP of 3 active hip tubercular cases decreased from 80.01 mg/L (range, 37.34-136.92 mg/L) at diagnosis time to 1.91 mg/L (range, 1.05-2.57 mg/L) at the final follow-up. The ESR and CRP of all patients had returned to normal level at the final follow-up. No prosthesis dislocation, loosening and neurovascular injury was found. CONCLUSIONS: THA is an effective and safe option for hip tuberculosis. The essentials for good outcome include early diagnosis, regular perioperative anti-tubercular chemotherapy, radical debridement of inflamed tissue and necrotic bone, staged-operation if necessary.

Association of cardiotrophin-like cytokine factor 1 levels in peripheral blood mononuclear cells with bone mineral density and osteoporosis in postmenopausal women.

BACKGROUND: Recent research has suggested that cardiotrophin-like cytokine factor 1 (CLCF1) may be an important regulator of bone homeostasis. Furthermore, a whole gene chip analysis suggested that the expression levels of CLCF1 in the peripheral blood mononuclear cells (PBMCs) were downregulated in postmenopausal women with osteoporosis. This study aimed to assess whether the expression levels of CLCF1 in PBMCs can reflect the severity of bone mass loss and the related fracture risk. METHODS: In all, 360 postmenopausal women, aged 50 to 80 years, were included in the study. A survey to evaluate the participants' health status, measurement of bone mineral density (BMD), routine blood test, and CLCF1 expression level test were performed. RESULTS: Based on the participants' bone health, 27 (7.5%), 165 (45.83%), and 168 (46.67%) participants were divided into the normal, osteopenia, and osteoporosis groups, respectively. CLCF1 protein levels in the normal and osteopenia groups were higher than those in the osteoporosis group. While the CLCF1 mRNA level was positively associated with the BMD of total femur (r = 0.169, p = 0.011) and lumbar spine (r = 0.176, p = 0.001), the protein level was positively associated with the BMD of the lumbar spine (r = 0.261, p < 0.001), femoral neck (r = 0.236, p = 0.001), greater trochanter (r = 0.228, p = 0.001), and Ward's triangle (r = 0.149, p = 0.036). Both the mRNA and protein levels were negatively associated with osteoporosis development (r = - 0.085, p = 0.011 and r = - 0.173, p = 0.014, respectively). The association between CLCF1 protein level and fracture risk was not significant after adjusting for BMD. CONCLUSIONS: To our knowledge, this is the first clinical study to show that CLCF1 expression levels in the PBMCs of postmenopausal women can reflect the amount of bone mass or the severity of bone mass loss.