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Previous studies have indicated that the nephrotoxicity induced by mesoporous silica nanoparticles (MSNs) is closely related to inflammation. Nuclear factor kappa B (NF-κB), a common rapid transcription factor associated with inflammation, plays an important role in the process of many kidney diseases. Acute toxicity assessment with a high-dose exposure is critical for the development of nanoparticle, as a part of standardized procedures for the evaluation of their toxicity. The present study was undertaken to observe the acute toxicity, predict the potential target organs of MSNs injury, and test the hypothesis that the NF-κB pathway plays a role in mediating the acute kidney injury and renal interstitial fibrosis in mice induced by MSNs. Balb/c mice were intraperitoneally injected with MSNs at concentrations of 150, 300, or 600 mg/kg. All of the animals were euthanized 2 and 12 days after exposure, and the blood and kidney tissues were collected for further studies. In vitro, the cytotoxicity, fibrosis markers, and NF-κB pathway were measured in a normal rat kidney cell line (NRK-52E). Acute kidney injury was induced by MSNs in mice after 2 days, some renal tubules regenerated and renal interstitial fibrosis was also observed. The expression of fibrosis markers and the nuclear translocation of NF-κB p65 in the kidney homogenates increased after exposure to MSNs. The in vitro study showed that MSNs cause cytotoxicity in NRK-52E cells and increased the expression of fibrosis markers. In addition, the NF-κB pathway could be induced, and inhibition of the NF-κB pathway could alleviate the fibrosis caused by MSNs. We conclude that inflammation is a major effector of the acute kidney toxicity induced by MSNs and results in renal interstitial fibrosis, which is mediated by the NF-κB signaling pathway.

Diabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in type 2 diabetic male mice and patients characterized by retinol overload, all-trans retinoic acid deficiency. By supplementing type 2 diabetic male mice with retinol or all-trans retinoic acid, we demonstrate that both cardiac retinol overload and all-trans retinoic acid deficiency promote diabetic cardiomyopathy. Mechanistically, by constructing cardiomyocyte-specific conditional retinol dehydrogenase 10-knockout male mice and overexpressing retinol dehydrogenase 10 in male type 2 diabetic mice via adeno-associated virus, we verify that the reduction in cardiac retinol dehydrogenase 10 is the initiating factor for cardiac retinol metabolism disorder and results in diabetic cardiomyopathy through lipotoxicity and ferroptosis. Therefore, we suggest that the reduction of cardiac retinol dehydrogenase 10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying diabetic cardiomyopathy. The current challenges for diabetic cardiomyopathy (DCM) are unclear mechanisms and no effective therapy in clinics. Here, the authors found that the decrease of cardiac retinol dehydrogenase 10 in type 2 diabetes leads to retinol metabolism disorder, cardiac lipid toxicity and cardiomyopathy development, suggesting that correcting the imbalance of cardiac retinol metabolism may be an effective strategy for the treatment of DCM.

Triptolide, the major active component of Tripterygium wilfordii Hook f. (TWHF), has a wide range of pharmacological activities. However, the toxicities of triptolide, particularly the hepatotoxicity, limit its clinical application. The hepatotoxicity of triptolide has not been well characterized yet. The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2) in triptolide-induced toxicity and whether activation of Nrf2 could protect against triptolide-induced hepatotoxicity. The results showed that triptolide caused oxidative stress and cell damage in HepG2 cells, and these toxic effects could be aggravated by Nrf2 knockdown or be counteracted by overexpression of Nrf2. Treatment with a typical Nrf2 agonist, sulforaphane (SFN), attenuated triptolide-induced liver dysfunction, structural damage, glutathione depletion and decrease in antioxidant enzymes in BALB/C mice. Moreover, the hepatoprotective effect of SFN on triptolide-induced liver injury was associated with the activation of Nrf2 and its downstream targets. Collectively, these results indicate that Nrf2 activation protects against triptolide-induced hepatotoxicity.

Studies of traits related to nitrogen (N)-use efficiency (NUE) in wheat cultivars are important for breeding N-efficient cultivars. Canopy structure has a major effect on NUE, as it determines the distribution of light and N. However, the mechanism by which canopy structure affects the distribution of light and N within the canopy remains unclear. The N-efficient winter wheat varieties YM49 and ZM27 and N-inefficient winter wheat varieties XN509 and AK58 were grown in the field under two N levels. Light transmittance was enhanced, and the leaf area index and photosynthetically active radiation were lower in the N-efficient cultivar population, which was characterized by moderately sized flag leaves, a low frequency of canopy leaf curling, a low light attenuation coefficient (KL), and high plant compactness. Reductions in the amount of shade increased the distribution of light and N resources to the middle and lower layers. The photosynthetic rate, transpiration rate, instant water-use efficiency, and canopy photosynthetic NUE were higher, N remobilization of the upper and middle canopy leaves was reduced, and the leaf N content was high in the N-efficient cultivars. A higher ratio of the N extinction coefficient (KN) to KL reflects the assimilation ability of the N-efficient winter wheat cultivars, resulting in improved canopy structure and distribution of light and N, higher 1000-grain weight and grain yield, and significantly increased light and NUE. An improved match between gradients of light and N in the leaf canopy promotes balanced C and N metabolism and reduces energy and nutrient losses. This should be a goal when breeding N-efficient wheat cultivars and implementing tillage regimes.

Mouse metabolic and behavioral phenotypes are tightly linked to strain, age and disease state, with distinct dysregulation in each disease model, underscoring the need for standardized preclinical experimental conditions.

As a midsized gene family conserved more by lineage than function, the typical plant terpene synthases (TPSs) could be a valuable tool to examine plant evolution. TPSs are pivotal in biosynthesis of gibberellins and related phytohormones as well as in formation of the extensive arsenal of specialized plant metabolites mediating ecological interactions whose production is often lineage specific. Yet the origin and early evolution of the TPS family is not well understood. Systematic analysis of an array of transcriptomes and sequenced genomes indicated that the TPS family originated after the divergence of land plants from charophytic algae. Phylogenetic and biochemical analyses support the hypothesis that the ancestral TPS gene encoded a bifunctional class I and II diterpene synthase producing the ent-kaurene required for phytohormone production in all extant lineages of land plants. Moreover, the ancestral TPS gene likely underwent duplication at least twice early in land plant evolution. Together these two gave rise to three TPS lineages leading to the extant TPS-c, TPS-e/f, and the remaining TPS (h/d/a/b/g) subfamilies, with the latter dedicated to secondary rather than primary metabolism while the former two contain those genes involved in ent-kaurene production. Nevertheless, parallel evolution from the ent-kaurene–producing class I and class II diterpene synthases has led to roles for TPS-e/f and -c subfamily members in secondary metabolism as well. These results clarify TPS evolutionary history and provide context for the role of these genes in producing the vast diversity of terpenoid natural products observed today in various land plant lineages.

Despite vast data support in DNA methylation (DNAm) biomarker discovery to facilitate health-care research, this field faces huge resource barriers due to preliminary unreliable candidates and the consequent compensations using expensive experiments. The underlying challenges lie in the confounding factors, especially measurement noise and individual characteristics. To achieve reliable identification of a candidate pool for DNAm biomarker discovery, we propose a Causality-driven Deep Regularization framework to reinforce correlations that are suggestive of causality with disease. It integrates causal thinking, deep learning, and biological priors to handle non-causal confounding factors, through a contrastive scheme and a spatial-relation regularization that reduces interferences from individual characteristics and noises, respectively. The comprehensive reliability of the proposed method was verified by simulations and applications involving various human diseases, sample origins, and sequencing technologies, highlighting its universal biomedical significance. Overall, this study offers a causal-deep-learning-based perspective with a compatible tool to identify reliable DNAm biomarker candidates, promoting resource-efficient biomarker discovery. DNA methylation is a promising method to identify biomarkers, but defining causality can be challenging. Here, the authors propose a causality driven regularization framework to reduce noise and identify potential causative factors.

Water lilies belong to the angiosperm order Nymphaeales. Amborellales, Nymphaeales and Austrobaileyales together form the so-called ANA-grade of angiosperms, which are extant representatives of lineages that diverged the earliest from the lineage leading to the extant mesangiosperms 1 – 3 . Here we report the 409-megabase genome sequence of the blue-petal water lily ( Nymphaea colorata ). Our phylogenomic analyses support Amborellales and Nymphaeales as successive sister lineages to all other extant angiosperms. The N. colorata genome and 19 other water lily transcriptomes reveal a Nymphaealean whole-genome duplication event, which is shared by Nymphaeaceae and possibly Cabombaceae. Among the genes retained from this whole-genome duplication are homologues of genes that regulate flowering transition and flower development. The broad expression of homologues of floral ABCE genes in N. colorata might support a similarly broadly active ancestral ABCE model of floral organ determination in early angiosperms. Water lilies have evolved attractive floral scents and colours, which are features shared with mesangiosperms, and we identified their putative biosynthetic genes in N. colorata . The chemical compounds and biosynthetic genes behind floral scents suggest that they have evolved in parallel to those in mesangiosperms. Because of its unique phylogenetic position, the N. colorata genome sheds light on the early evolution of angiosperms. The genome of the tropical blue-petal water lily Nymphaea colorata and the transcriptomes from 19 other Nymphaeales species provide insights into the early evolution of angiosperms.

A transient multibody dynamics simulation of rolling-element bearings is the basis for the design of high-speed rotating machinery; however, the established solvers are proprietary, cannot be used with automatic differentiation, and offer no built-in measure of their own physical consistency. We present OpenBEARD, an open-source, fully differentiable transient dynamics solver for angular-contact ball bearings. The solver steps a 40+13Z-component state (inner ring, cage, and Z balls with quaternion attitude, plus guide-patch, lumped-thermal, and energy-audit states) forward in time under coupled Hertzian contact, Hamrock–Dowson and full-multigrid elastohydrodynamic lubrication, thermal–elastohydrodynamic traction, and centrifugal/press-fit clearance models, using nondimensionalized implicit stiff time integration. A built-in metriplectic conservation audit checks energy closure, the second law per dissipation channel, and the gyroscopic-power identity at every output step. OpenBEARD is cross-verified against two published ADORE references of Gupta. For a high-speed NASA angular-contact ball bearing, the quasi-static contact loads, angles, stresses, and centrifugal force match the published values to within 0.3%, and the ball spin and orbital velocities and the spin-axis orientation to ≤0.1%. The inner-race spin-to-roll ratio—a slip-derived secondary quantity that is the most model-sensitive metric in this class of solvers—differs from the NASA quasi-static reference by 8.8%. In the separate caged BallBearingTestCase benchmark, the corresponding quasi-static difference is 3.2%, and the transient settled value is ≈16% above the ADORE step-100 snapshot; these bounded offsets reflect different spin-moment constitutive models. The BallBearingTestCase comparison—a caged bearing under combined thrust and radial load—matches the per-ball contact angles and loads to within 0.23% RMS, and a single published dynamic snapshot (step 100) agrees with the transient contact mechanics to within a few percent. The built-in energy-closure residual stays of order 10−5 with no second-law violations. In the fully transient regime, race control emerges as a dynamical attractor of the coupled traction balance—ball-spin states perturbed by ±12% converge to a single outer-race-control solution—rather than the kinematic hypothesis assumed by quasi-static theory. OpenBEARD is released under the MIT license.

The current standard treatment for locally advanced rectal cancer is based on a multimodal comprehensive treatment combined with preoperative neoadjuvant chemoradiation and complete surgical resection of the entire mesorectal cancer. For ultra-low cases and cases with lateral lymph node metastasis, due to limitations in laparoscopic technology, the difficulties of operation and incidence of intraoperative complications are always difficult to overcome. Robotic surgery for the treatment of rectal cancer is an emerging technique that can overcome some of the technical drawbacks posed by conventional laparoscopic approaches, improving the scope and effect of radical operations. However, evidence from the literature regarding its oncological safety and clinical outcomes is still lacking. This brief review summarized the current status of robotic technology in rectal cancer therapy from the perspective of several mainstream surgical methods, including robotic total mesorectal excision (TME), robotic transanal TME, robotic lateral lymph node dissection, and artificial intelligence, focusing on the developmental direction of robotic approach in the field of minimally invasive surgery for rectal cancer in the future.