Quantitatively analyzing the dissociation and release of disulfide-containing organic nanoparticles.

The disintegration of nanoparticles and drug release are important and imperative for nanoparticle formulations of therapeutic agents. However, quantitatively monitoring the drug release of nanomedicines is a major challenge. In this work, boron-dipyrromethene (BDP) was applied as a model drug to study the disassembly of nanoparticles and drug release. BDP dimers with disulfide and ester bonds were synthesized, and their nanoparticles were made. The accurate analysis of bond breaking in BDP nanoparticles could not be realized by using confocal laser scanning microscopy. Hence, the possible products after bond cleavage were quantified by using liquid chromatography tandem mass spectrometry (LC-MS/MS). BDP nanoparticles could be endocytosed into cancer cells, and the disulfide bonds and ester bonds were broken to promote the disassociation of nanoparticles and BDP release. Then, near-infrared BDP nanoparticles were investigated in live mice by near-infrared fluorescence imaging and LC-MS/MS. The release of BDP was low (<10%) and BDP maintained the original dimer structure in vivo, which showed that the bond breaking for BDP nanoparticles was difficult in vivo. These results could help us understand the breaking law of disulfide bonds and ester bonds in nanoparticles and are beneficial for developing practical new drug formulations.

A Prediction Model for Assessing the Efficacy of Thermal Ablation in Treating Benign Thyroid Nodules ≥ 2 cm: A Multi-Center Retrospective Study.

OBJECTIVES: To develop and validate a prediction model utilizing clinical and ultrasound (US) data for preoperative assessment of efficacy following US-guided thermal ablation (TA) in patients with benign thyroid nodules (BTNs) ≥ 2 cm. MATERIALS AND METHODS: We retrospectively assessed 962 patients with 1011 BTNs who underwent TA at four tertiary centers between May 2018 and July 2022. Ablation efficacy was categorized into therapeutic success (volume reduction rate [VRR] > 50%) and non-therapeutic success (VRR ≤ 50%). We identified independent factors influencing the ablation efficacy of BTNs ≥ 2 cm in the training set using multivariate logistic regression. On this basis, a prediction model was established. The performance of model was further evaluated by discrimination (area under the curve [AUC]) in the validation set. RESULTS: Of the 1011 nodules included, 952 (94.2%) achieved therapeutic success at the 12-month follow-up after TA. Independent factors influencing VRR > 50% included sex, nodular composition, calcification, volume, and largest diameter (all p < 0.05). The prediction equation was established as follows: p = 1/1 + Exp∑[8.113 -2.720 × (if predominantly solid) -2.790 × (if solid) -1.275 × (if 10 mL < volume ≤ 30mL) -1.743 × (if volume > 30 mL) -1.268 × (if with calcification) -2.859 × (if largest diameter > 3 cm) +1.143 × (if female)]. This model showed great discrimination, with AUC of 0.908 (95% confidence interval [CI]: 0.868-0.947) and 0.850 (95% CI: 0.748-0.952) in the training and validation sets, respectively. CONCLUSIONS: A clinical prediction model was successfully developed to preoperatively predict the therapeutic success of BTNs larger than 2 cm in size following US-guided TA. This model aids physicians in evaluating treatment efficacy and devising personalized prognostic plans.

How the root bacterial community of Ficus tikoua responds to nematode infection: enrichments of nitrogen-fixing and nematode-antagonistic bacteria in the parasitized organs.

Plant-parasitic nematodes (PPNs) are among the most damaging pathogens to host plants. Plants can modulate their associated bacteria to cope with nematode infections. The tritrophic plant-nematode-microbe interactions are highly taxa-dependent, resulting in the effectiveness of nematode agents being variable among different host plants. Ficus tikoua is a versatile plant with high application potential for fruits or medicines. In recent years, a few farmers have attempted to cultivate this species in Sichuan, China, where parasitic nematodes are present. We used 16S rRNA genes to explore the effects of nematode parasitism on root-associated bacteria in this species. Our results revealed that nematode infection had effects on both endophytic bacterial communities and rhizosphere communities in F. tikoua roots, but on different levels. The species richness increased in the rhizosphere bacterial communities of infected individuals, but the community composition remained similar as compared with that of healthy individuals. Nematode infection induces a deterministic assembly process in the endophytic bacterial communities of parasitized organs. Significant taxonomic and functional changes were observed in the endophytic communities of root knots. These changes were characterized by the enrichment of nitrogen-fixing bacteria, including Bradyrhizobium, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, and nematode-antagonistic bacteria, such as Pseudonocardia, Pseudomonas, Steroidobacter, Rhizobacter, and Ferrovibrio. Our results would help the understanding of the tritrophic plant-nematode-bacterium interactions in host plants other than dominant crops and vegetables and would provide essential information for successful nematode management when F. tikoua were cultivated on large scales.

The microgeo: an R package rapidly displays the biogeography of soil microbial community traits on maps.

Many R packages provide statistical approaches for elucidating the diversity of soil microbes, yet they still struggle to visualize microbial traits on a geographical map. This creates challenges in interpreting microbial biogeography on a regional scale, especially when the spatial scale is large or the distribution of sampling sites is uneven. Here, we developed a lightweight, flexible, and user-friendly R package called microgeo. This package integrates many functions involved in reading, manipulating, and visualizing geographical boundary data; downloading spatial datasets; and calculating microbial traits and rendering them onto a geographical map using grid-based visualization, spatial interpolation, or machine learning. Using this R package, users can visualize any trait calculated by microgeo or other tools on a map and can analyze microbiome data in conjunction with metadata derived from a geographical map. In contrast to other R packages that statistically analyze microbiome data, microgeo provides more-intuitive approaches in illustrating the biogeography of soil microbes on a large geographical scale, serving as an important supplement to statistically driven comparisons and facilitating the biogeographic analysis of publicly accessible microbiome data at a large spatial scale in a more convenient and efficient manner. The microgeo R package can be installed from the Gitee (https://gitee.com/bioape/microgeo) and GitHub (https://github.com/ChaonanLi/microgeo) repositories. Detailed tutorials for the microgeo R package are available at https://chaonanli.github.io/microgeo.

Effects of guanidino acetic acid and betaine supplementation on growth, dietary nutrient digestion and intestinal creatine metabolism in sheep.

BACKGROUND: The intestine of young ruminants is in the developmental stage and has weaker resistance to the changes of external environment. Improving intestinal health is vital to promoting growth of young ruminants. This study investigated effects of guanidino acetic acid (GAA) and rumen-protected betaine (RPB) supplementation on growth, dietary nutrient digestion and GAA metabolism in the small intestine of sheep. METHODS: Eighteen healthy Kazakh rams (27.46 ± 0.10 kg of body weight and 3-month old) were categorized into control, test group I and test group II, which were fed a basal diet, 1500 mg/kg GAA and 1500 mg/kg GAA + 600 mg/kg RPB, respectively. RESULTS: Compared with control group, test group II had increased (p < 0.05) average daily gain, plasma creatine level, ether extract (EE) and phosphorus digestibility on day 30. On day 60, the EE apparent digestibility, jugular venous plasma GAA, GAA content in the duodenal mucosa and GAA content in the jejunal and ileal mucosa of test group II were higher (p < 0.05) than other groups. Transcriptome analysis revealed that the differentially expressed genes (DEGs) involved in the duodenal pathways of oxidative phosphorylation and non-alcoholic fatty liver disease were significantly altered in test group II versus test group I (p < 0.05). Moreover, in the jejunum, the MAPK signalling pathway, complement and coagulation cascade and B-cell receptor signalling pathway were significantly enriched, with ATPase, solute carrier transporter protein, DHFR, SI, GCK, ACACA and FASN being the significantly DEGs (p < 0.05). CONCLUSION: Dietary supplementation of RPB on top of GAA in sheep diets may promote sheep growth and development by improving the body's energy, amino acid, glucose and lipid metabolism capacity.

Consistent community assembly but contingent species pool effects drive ß-diversity patterns of multiple microbial groups in desert biocrust systems.

One of the key goals of ecology is to understand how communities are assembled. The species co-existence theory suggests that community ß-diversity is influenced by species pool and community assembly processes, such as environmental filtering, dispersal events, ecological drift and biotic interactions. However, it remains unclear whether there are similar ß-diversity patterns among different soil microbial groups and whether all these mechanisms play significant roles in mediating ß-diversity patterns. By conducting a broad survey across Chinese deserts, we aimed to address these questions by investing biological soil crusts (biocrusts). Through amplicon-sequencing, we acquired ß-diversity data for multiple microbial groups, that is, soil total bacteria, diazotrophs, phoD-harbouring taxa, and fungi. Our results have shown varying distance decay rates of ß-diversity across microbial groups, with soil total bacteria showing a weaker distance-decay relationship than other groups. The impact of the species pool on community ß-diversity varied across microbial groups, with soil total bacteria and diazotrophs being significantly influenced. While the contributions of specific assembly processes to community ß-diversity patterns varied among different microbial groups, significant effects of local community assembly processes on ß-diversity patterns were consistently observed across all groups. Homogenous selection and dispersal limitation emerged as crucial processes for all groups. Precipitation and soil C:P were the key factors mediating ß-diversity for all groups. This study has substantially advanced our understanding of how the communities of multiple microbial groups are structured in desert biocrust systems.

Microbial perspective on restoration of degraded urban soil using ornamental plants.

The urban soil where abandoned buildings are demolished is barren and structurally poor, and this degraded soil requires restoration. Ornamental plants enhance the urban environment, increase biodiversity, and affect soil physicochemical properties, microbial diversity; however, their effects remain unclear. Thus, in this study, a mixed-planting meadow consisting of 14 perennial ornamental flower species, including Iris tectorum, Iris lacteal, and Patrinia scabiosaefolia, etc. Was planted at a demolition site with sewage-contaminated soil in Beijing. Simultaneously, a single-planting lawn of I. tectorum was established in a nearby park. We aimed to examine soil physicochemical properties, sequence soil bacterial 16S rRNA and fungal ITS amplicons, and analyze soil microbial diversity and community structure at both sites at five time points in the year after planting, To explore the effect of herbaceous ornamental plants on degraded urban soil, we used FAPROTAX and FUNGuild to predict bacterial and fungal functions, the bin-based null model to evaluate the soil microbial community, and random matrix theory to construct soil microbial molecular networks. The mixed-planting meadow produced a visually appealing landscape and dynamic seasonal enrichment, significantly increasing soil total nitrogen (TN) and organic matter (SOM) contents by 1.99 and 1.21 times, respectively. TN had a positive correlation with soil microbial α diversity and community structure. Dominant phyla at both sites included Proteobacteria, Actinobacteria, and Ascomycota. Although soil microorganisms were primarily influenced by stochastic processes, stochasticity was notably higher in the mixed-planting meadow than in the single-planting lawn. The mixed-planting meadow significantly increased the relative abundance of beneficial microorganisms, improving nitrification and aerobic ammonium oxidation of soil bacteria, as well as symbiotroph of fungi. No significant changes were observed in the single-planting lawn. The mixed-planting meadow established a complex soil microbial molecular network, enhancing the correlation between bacteria and fungi and increasing the number of key microorganisms. Our findings suggest the potential of mixed-planting meadow in restoring degraded urban soils by influencing the soil microbial community and enhancing the ecological service function. Our study provides theoretical support for applying mixed-planting meadow communities to improve the soil environment of urban green spaces.

Comparative genomics reveals the adaptation of ammonia-oxidising Thaumarchaeota to arid soils.

Thaumarchaeota are predominant in oligotrophic habitats such as deserts and arid soils, but their adaptations to these arid conditions are not well understood. In this study, we assembled 23 Thaumarchaeota genomes from arid and semi-arid soils collected from the Inner Mongolia Steppe and the Qinghai-Tibet Plateau. Using a comparative genomics approach, integrated with 614 Thaumarchaeota genomes from public databases, we identified the traits and evolutionary forces that contribute to their adaptations to aridity. Our results showed that the newly assembled genomes represent an early diverging group within the lineage of ammonia-oxidising Thaumarchaeota. While the genomic functions previously identified in arid soil lineages were conserved across terrestrial, shallow-ocean and deep-ocean lineages, several traits likely contribute to Thaumarchaeota's adaptation to aridity. These include chlorite dismutase, arsenate reductase, V-type ATPase and genes dealing with oxidative stresses. The acquisition and loss of traits at the last common ancestor of arid soil lineages may have facilitated the specialisation of Thaumarchaeota in arid soils. Additionally, the acquisition of unique adaptive traits, such as a urea transporter, Ca2+ :H+ antiporter, mannosyl-3-phosphoglycerate synthase and phosphatase, DNA end-binding protein Ku and phage shock protein A, further distinguishes arid soil Thaumarchaeota. This study provides evidence for the adaptations of Thaumarchaeota to arid soil, enhancing our understanding of the nitrogen and carbon cycling driven by Thaumarchaeota in drylands.

Synthesis and Characterization of Mesoporous Silica Nanoparticles Loaded with P-Cymene against Rice Bacterial Blight.

Mesoporous silica nanoparticles (MSNs) can be used as carrier materials for the controlled release of pesticides while reducing their negative environmental impact. In this study, we screened an active ingredient, p-cymene (PC), with an excellent inhibitory effect on rice bacterial blight. Subsequently, the PC was successfully loaded onto MSNs via physisorption (PC@MSNs). PC@MSNs, characterized by a regular spherical shape, smooth surface, and an MSN average size of 262.9 nm, achieved an 8.6% drug loading capacity. The release kinetics of the PC from the PC@MSNs demonstrated a sustained release (288 h) pattern influenced by drug diffusion. The efficacy of the PC@MSNs against Xanthomonas oryzae pv. Oryzae paralleled those of PC. Acute toxicity assays revealed that the PC@MSNs were less toxic to aquatic life (LC50 = 257.867 mg/L) and that the formulation showed no adverse effects on rice seedling growth. In summary, these results suggest that PC@MSNs can broaden PC's scope of application in managing rice diseases.

Vegetation restoration restrains rill erosion on slag heaps in high-altitude goldfields.

Soil erosion leads to soil degradation and depletion of land resources, posing a significant threat to industrial production and ecological sustainability. In high-altitude regions, rill erosion is the main form of soil erosion in mining areas, however, our understanding of morphology and developmental characteristics of rills and the mechanisms influencing them remains limited. In this study, data were collected from 96 rill plots across two gold mines in the eastern Tibetan Plateau according to vegetation restoration modes (natural restoration (CK) and planted with Elymus dahuricus (ED), Medicago sativa (MS), and multi-plant mixed (Avena fatua L. + Elymus dahuricus + Medicago sativa + Oxytropis coerulea, MM)) and restoration periods (1 year, 3 years, 4 years, and 6 years). We investigated the variations of 7 indicators that can reveal rill morphological and developmental characteristics across different restoration modes and restoration periods, and utilized a partial least squares structural equation model (PLS-SEM) to analyze the effects of 15 indicators from topography, soil, and vegetation on rill erosion modulus (REM). The results indicated that artificial vegetation restoration effectively restrained rill development, notably by decreasing the frequency of wider (>15 cm) and deeper (>10 cm) rills when compared to CK plots. Planting MM and ED exhibited greater efficacy in controlling rill erosion than planting MS. However, the effectiveness of planting ED in controlling rill erosion gradually weakened with time, while MM consistently maintained a strong inhibitory effect. Topographic features, soil texture, and vegetation significantly influenced the REM through direct or indirect effects. Plant root functional traits were the main driving factors in reducing REM, affecting not only REM directly but also influencing vegetation-induced soil properties to indirectly effect REM.

Analysis of the protective efficacy of approved COVID-19 vaccines against Omicron variants and the prospects for universal vaccines.

By the end of 2022, different variants of Omicron had rapidly spread worldwide, causing a significant impact on the Coronavirus disease 2019 (COVID-19) pandemic situation. Compared with previous variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), these new variants of Omicron exhibited a noticeable degree of mutation. The currently developed platforms to design COVID-19 vaccines include inactivated vaccines, mRNA vaccines, DNA vaccines, recombinant protein vaccines, virus-like particle vaccines, and viral vector vaccines. Many of these platforms have obtained approval from the US Food and Drug Administration (FDA) or the WHO. However, the Omicron variants have spread in countries where vaccination has taken place; therefore, the number of cases has rapidly increased, causing concerns about the effectiveness of these vaccines. This article first discusses the epidemiological trends of the Omicron variant and reviews the latest research progress on available vaccines. Additionally, we discuss progress in the development progress and practical significance of universal vaccines. Next, we analyze the neutralizing antibody effectiveness of approved vaccines against different variants of Omicron, heterologous vaccination, and the effectiveness of multivalent vaccines in preclinical trials. We hope that this review will provide a theoretical basis for the design, development, production, and vaccination strategies of novel coronavirus vaccines, thus helping to end the SARS-CoV-2 pandemic.

An updated review of epidemiological characteristics, immune escape, and therapeutic advances of SARS-CoV-2 Omicron XBB.1.5 and other mutants.

The rapid evolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the emergence of new variants with different genetic profiles, with important implications for public health. The continued emergence of new variants with unique genetic features and potential changes in biological properties poses significant challenges to public health strategies, vaccine development, and therapeutic interventions. Omicron variants have attracted particular attention due to their rapid spread and numerous mutations in key viral proteins. This review aims to provide an updated and comprehensive assessment of the epidemiological characteristics, immune escape potential, and therapeutic advances of the SARS-CoV-2 Omicron XBB.1.5 variant, as well as other variants.

Functional conservation of microbial communities determines composition predictability in anaerobic digestion.

A major challenge in managing and engineering microbial communities is determining whether and how microbial community responses to environmental alterations can be predicted and explained, especially in microorganism-driven systems. We addressed this challenge by monitoring microbial community responses to the periodic addition of the same feedstock throughout anaerobic digestion, a typical microorganism-driven system where microorganisms degrade and transform the feedstock. The immediate and delayed response consortia were assemblages of microorganisms whose abundances significantly increased on the first or third day after feedstock addition. The immediate response consortia were more predictable than the delayed response consortia and showed a reproducible and predictable order-level composition across multiple feedstock additions. These results stood in both present (16 S rRNA gene) and potentially active (16 S rRNA) microbial communities and in different feedstocks with different biodegradability and were validated by simulation modeling. Despite substantial species variability, the immediate response consortia aligned well with the reproducible CH4 production, which was attributed to the conservation of expressed functions by the response consortia throughout anaerobic digestion, based on metatranscriptomic data analyses. The high species variability might be attributed to intraspecific competition and contribute to biodiversity maintenance and functional redundancy. Our results demonstrate reproducible and predictable microbial community responses and their importance in stabilizing system functions.

Implications of vitamin D for flesh quality of grass carp (Ctenopharyngodon idella): antioxidant ability, nutritional value, sensory quality, and myofiber characteristics.

BACKGROUND: Muscle represents a unique and complex system with many components and comprises the major edible part of animals. Vitamin D is a critical nutrient for animals and is known to enhance calcium absorption and immune response. In recent years, dietary vitamin D supplementation in livestock has received increased attention due to biological responses including improving shear force in mammalian meat. However, the vitamin D acquisition and myofiber development processes in fish differ from those in mammals, and the effect of vitamin D on fish flesh quality is poorly understood. Here, the influence of dietary vitamin D on fillet quality, antioxidant ability, and myofiber development was examined in grass carp (Ctenopharyngodon idella). METHODS: A total of 540 healthy grass carp, with an initial average body weight of 257.24 ± 0.63 g, were allotted in 6 experimental groups with 3 replicates each, and respectively fed corresponding diets with 15.2, 364.3, 782.5, 1,167.9, 1,573.8, and 1,980.1 IU/kg vitamin D for 70 d. RESULTS: Supplementation with 1,167.9 IU/kg vitamin D significantly improved nutritional value and sensory quality of fillets, enhancing crude protein, free amino acid, lipid, and collagen contents; maintaining an ideal pH; and reducing lactate content, shear force, and cooking loss relative to respective values in the control (15.2 IU/kg) group. Average myofiber diameter and the frequency of myofibers > 50 µm in diameter increased under supplementation with 782.5-1,167.9 IU/kg vitamin D. Levels of oxidative damage biomarkers decreased, and the expression of antioxidant enzymes and nuclear factor erythroid 2-related factor 2 signaling molecules was upregulated in the 1,167.9 IU/kg vitamin D treatment compared to respective values in the control group. Furthermore, vitamin D supplementation activated cell differentiation by enhancing the expression of myogenic regulatory factors and myocyte enhancer factors compared to that in the control group. In addition, supplementation with 1,167.9 IU/kg vitamin D improved protein deposition associated with protein synthesis molecule (target of rapamycin) signaling and vitamin D receptor paralogs, along with inhibition of protein degradation (forkhead box protein 1) signaling. CONCLUSIONS: Overall, the results demonstrated that vitamin D strengthened antioxidant ability and myofiber development, thereby enhancing nutritional value and sensory quality of fish flesh. These findings suggest that dietary vitamin D supplementation is conducive to the production of nutrient-rich, high quality aquaculture products.

Physiological and proteomic changes of Castanopsis fissa in response to drought stress.

Castanopsis fissa is a native, broadleaf tree species in Guangdong with characteristics of barrenness and fast growth and is often used as a pioneer species for vegetation restoration with excellent ecological benefits. To explore the response of C.fissa to drought, this study investigated the drought tolerance mechanism of C.fissa using physiological and proteomic assessments. Using a potted continuous drought experimental method with normal water supply as a control, we measured photosynthetic parameters, antioxidant enzyme activities, and osmoregulatory substances of C. fissa in response to drought stress for 1 to 4 weeks, respectively. In addition, we used TMT quantitative proteomics to identify differentially expressed proteins (DEPs) between the drought-stress-treated C. fissa leaves and the control leaves. With the extension of drought stress time, the photosynthetic indexes and peroxidase (POD) activity of C. fissa leaves showed a decreasing trend. The malondialdehyde (MDA) content; superoxide Dismutase (SOD) and catalase (CAT) activities; and proline (Pro), soluble sugar (SS) and soluble protein (SP) contents showed an overall increasing trend, all of which reached significant differences at 4 w of stress. We identified 177 and 529 DEPs in the 2 and 4 weeks drought-stress leaves, respectively, in reference to the control leaves. These DEPs were closely related to physiological metabolic processes such as photosynthesis, energy and carbohydrate metabolism, stress response and defense, transcriptional regulation, and signal ion transduction. Drought stress mainly affects photosynthesis, carbohydrate metabolism, and protein synthesis and degradation in C. fissa leaves. At 2 weeks of stress, the expression of carbon metabolism, pyruvate metabolism and ribosome-related proteins was significantly changed, however, and at 4 weeks of stress, protein processing in the endoplasmic reticulum and spliceosome-related proteins were significantly increased in plant leaves. To alleviate the effect of water unavailability, the drought-stressed C.fissa leaves increased its oxidative protective enzyme system to eliminate excess reactive oxygen species (ROS) and also increased its Pro and SP contents to maintain the intracellular osmotic potential balance.

Topography shapes the carbon allocation patterns of alpine forests.

Topography plays a crucial role in determining the structure of alpine forests, as it restricts the availability of nutrients and water necessary for plant growth. Nevertheless, our information on how variations in forest carbon allocation patterns driven by fine-scale topography are influenced by broader-scale environmental contexts is limited. In the northern Tibetan Plateau, we combined field data from 89 forest plots with a high-resolution (1 m2) digital elevation model (DEM) and utilized a linear mixed-effects model to investigate how microtopography (characterized by slope, aspect, and topographic wetness index (TWI)) and broader-scale environmental context (characterized by elevation) and their interactions affect the carbon allocation patterns of alpine forest. Our results revealed that at low and high elevations with pronounced subsurface resource limitations, plants tend to allocate a higher proportion of carbon to the root system and have lower aboveground carbon stocks (ACS). Microtopographic heterogeneity significantly influenced the carbon allocation patterns of forest, with the intensity and direction of these effects varying across the environmental gradient. At low elevations, topographically wetter and northerly microhabitats had higher ACS and lower ratios of below- and aboveground carbon stocks (RBA); however, at high elevations, topographically drier and southerly microhabitats had higher ACS and lower RBA. TWI and aspect had the weakest effect on ACS and RBA in the mid-elevations. The relationship between slope and ACS and RBA was significantly positive but not evidently related to the broader-scale environmental gradient.

RING finger E3 ubiquitin ligase gene TaAIRP2-1B controls spike length in wheat.

E3 ubiquitin ligase genes play important roles in the regulation of plant development. They have been well studied in plants, but have not been sufficiently investigated in wheat. Here, we identified a highly expressed RING finger E3 ubiquitin ligase gene TaAIRP2-1B (ABA-insensitive RING protein 2) in wheat spike. Sequence polymorphism and association analysis showed that TaAIRP2-1B is significantly associated with spike length under various conditions. The genotype with haplotype Hap-1B-1 of TaAIRP2-1B has a longer spike than that of Hap-1B-2, and was positively selected in the process of wheat breeding in China. Moreover, the TaAIRP2-1B-overexpressing rice lines have longer panicles compared with wild-type plants. The expression levels of TaAIRP2-1B in Hap-1B-1 accessions were higher than in Hap-1B-2 accessions. Further study revealed that the expression of TaAIRP2-1B was negatively regulated by TaERF3 (ethylene-responsive factor 3) via binding to the Hap-1B-2 promoter, but not via binding of Hap-1B-1. Additionally, several candidate genes interacting with TaAIRP2-1B were obtained by screening the cDNA library of wheat in yeast cells. It was found that TaAIRP2-1B interacted with TaHIPP3 (heavy metal-associated isoprenylated protein 3) and promoted TaHIPP3 degradation. Our study demonstrates that TaAIRP2-1B controls spike length, and the haplotype Hap-1B-1 of TaAIRP2-1B is a favorable natural variation for spike length enhancement in wheat. This work also provides genetic resources and functional markers for wheat molecular breeding.

A Paclitaxel Prodrug with Copper Depletion for Combined Therapy toward Triple-Negative Breast Cancer.

Tuning the content of copper is of great significance for the treatment of cancer and neurodegenerative diseases. Herein, we synthesized a redox-responsive paclitaxel (PTX) prodrug by conjugating PTX with a copper chelator through a disulfide bond. The as-fabricated prodrug (PSPA) showed specific chelation toward copper ions and could assemble with distearoyl phosphoethanolamine-PEG2000 to form stable nanoparticles (PSPA NPs) in aqueous media. Upon being internalized by tumor cells, PSPA NPs could respond to high levels of redox-active species inside cells and efficiently release PTX. The copper chelator could increase oxidative stress- and abnormal metabolism-induced cell death through intracellular copper depletion. The combination of chemotherapy and copper depletion therapy generated an enhanced therapeutic outcome toward triple-negative breast cancer with an ignorable systemic toxicity. Our work may provide insight into the combination of metabolic regulation and chemotherapy for combating malignant tumors.

Discovery of an OTUD3 inhibitor for the treatment of non-small cell lung cancer.

The ubiquitin-proteasome system (UPS) controls protein turnover, and its dysfunction contributes to human diseases including cancer. Deubiquitinating enzymes (DUBs) remove ubiquitin from proteins to maintain their stability. Inhibition of DUBs could induce the degradation of selected oncoproteins and has therefore become a potential therapeutic strategy for cancer. The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer. Here, we report a small-molecule inhibitor of OTUD3 (named OTUDin3) by computer-aided virtual screening and biological experimental verification. OTUDin3 exhibited pronounced antiproliferative and proapoptotic effects by inhibiting deubiquitinating activity of OTUD3 in non-small-cell lung cancer (NSCLC) cell lines. Moreover, OTUDin3 efficaciously inhibited growth of lung cancer xenografts in mice. In summary, our results support OTUDin3 as a potent inhibitor of OTUD3, the inhibition of which may be a promising therapeutic strategy for NSCLC.