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Mitochondrial quality control is critical for cardiac homeostasis as these organelles are responsible for generating most of the energy needed to sustain contraction. Dysfunctional mitochondria are normally degraded via intracellular degradation pathways that converge on the lysosome. Here, we identified an alternative mechanism to eliminate mitochondria when lysosomal function is compromised. We show that lysosomal inhibition leads to increased secretion of mitochondria in large extracellular vesicles (EVs). The EVs are produced in multivesicular bodies, and their release is independent of autophagy. Deletion of the small GTPase Rab7 in cells or adult mouse heart leads to increased secretion of EVs containing ubiquitinated cargos, including intact mitochondria. The secreted EVs are captured by macrophages without activating inflammation. Hearts from aged mice or Danon disease patients have increased levels of secreted EVs containing mitochondria indicating activation of vesicular release during cardiac pathophysiology. Overall, these findings establish that mitochondria are eliminated in large EVs through the endosomal pathway when lysosomal degradation is inhibited. Mitochondrial quality control is critical for cellular homeostasis and survival. Here, the authors identify that defective mitochondria can be eliminated via secretion in large extracellular vesicles when internal lysosomal degradation is compromised.

Thiazide diuretics are widely used for the management of hypertension. In recent years, it has been actively debated that there is interchangeability of thiazide‐type diuretics hydrochlorothiazide and thiazide‐like diuretics including indapamide and chlorthalidone for the treatment of hypertension. With the purpose of seeking out the best thiazide diuretic for clinicians, we summarized the existing evidence on the two types of drugs and conducted a meta‐analysis on their efficacy in lowering blood pressure and effects on blood electrolyte, glucose and total cholesterol. Twelve trials were identified: five based on the comparison of indapamide versus hydrochlorothiazide and seven based on the chlorthalidone versus hydrochlorothiazide. In the meta‐analysis of blood pressure reduction, thiazide‐like diuretics seemed to further reduce systolic BP ([95% CI]; −5.59 [−5.69, −5.49]; P < 0.001) and diastolic BP ([95% CI]; −1.98 [−3.29, −0.66]; P = 0.003). Meanwhile, in the analysis of side effects, the incidence of hypokalemia ([95% CI]; 1.58 [0.80, 3.12]; P = 0.19), hyponatremia ([95% CI]; −0.14 [−0.57, 0.30], P = 0.54), change of blood glucose ([95% CI];0.13 [−0.16, 0.41], P = 0.39) and total cholesterol ([95% CI]; 0.13 [−0.16, 0.41], P = 0.39) showed that there is no statistical significant differences between the two groups of drugs. In conclusion, using thiazide‐like diuretics is superior to thiazide‐type diuretics in reducing blood pressure without increasing the incidence of hypokalemia, hyponatraemia and any change of blood glucose and serum total cholesterol.

This article reports a potential lava tube observed at ∼130 m depth of the lunar farside by Lunar Penetrating Radar data. However, a possible scenario with a kind of dry and low-density materials connected with a basaltic boulder or lava flow cannot be excluded. If the lava tube is valid, it is at the edge of a huge paleo-depression with a maximum width of ∼26 m and a height of ∼16 m. It presents bright and phase-reversed reflections, a depressed roof, and asymmetrical reflected power on the radargram. Estimation results of the loss tangent provide evidence for it and simultaneously reveal the residual basalt material in the western region of the tube. The ancient lava flow is thought to postdate the adjacent ejecta and has high FeO+TiO2 content. Comprehensive analyses demonstrate that the lava flow inflation, the looseness of the adjacent ejecta, and the depressed paleo-terrain may cause horizontal erosion, subsequent deceleration, and final residue of the lava. Subsequent differential compaction of overlying strata resulted in its deformation and the accumulation of pyroclastic materials in it. The results may provide unprecedented knowledge about the formation mechanisms and interior structures of lava tubes on the Moon.

Amphibious plants escape submergence by plastically accelerating shoot growth, yet the mechanism underlying this convergent strategy remains unclear. Here, we demonstrate that PHYTOCHROME A (PHYA), a light photoreceptor, acts as a central regulator of the contrasting submergence escape capacities between amphibious Alternanthera philoxeroides and its terrestrial congener A. pungens . PHYA is distinctively regulated upon submergence in two congeners and negatively regulates submergence-induced elongation. Crucially, we find a cis -regulatory element (CRE) variant in the PHYA promoter between two congeners, which governs EIN3-dependent transcriptional repression and drives species-specific PHYA expression. Expanded investigation unveils phyletic retention of this CRE in other amphibious species, providing preliminary evidence for convergent evolution in the submergence escape capacity through independent co-option of the same CREs. Our findings demonstrate a role of PHYA in mediating submergence responses, deepen the understanding of the molecular basis for plant secondary aquatic adaptation, and inform flood-resilient crops engineering via cis -regulatory manipulation. How did amphibious plants evolve the convergent strategy to escape submergence by fast shoot elongation? Yang et al. reveal the pivotal role of a cis -regulatory element in the PHYA promoter in promoting submergence-induced plastic growth of amphibious plants.

Aging is associated with structural and functional changes in the heart and is a major risk factor in developing cardiovascular disease. Many recent studies have focused on increasing our understanding of the basis of aging at the cellular and molecular levels in various tissues, including the heart. It is known that there is an age-related decline in cellular quality control pathways such as autophagy and mitophagy, which leads to accumulation of potentially harmful cellular components in cardiac myocytes. There is evidence that diminished autophagy and mitophagy accelerate the aging process, while enhancement preserves cardiac homeostasis and extends life span. Here, we review the current knowledge of autophagy and mitophagy in aging and discuss how age-associated alterations in these processes contribute to cardiac aging and age-related cardiovascular diseases.

As one of the main payloads mounted on the Yutu-2 rover of Chang’E-4 probe, lunar penetrating radar (LPR) aims to map the subsurface structure in the Von Kármán crater. The field LPR data are generally masked by clutters and noises of large quantities. To solve the noise interference, dozens of filtering methods have been applied to LPR data. However, these methods have their limitations, so noise suppression is still a tough issue worth studying. In this article, the denoising convolutional neural network (CNN) framework is applied to the noise suppression and weak signal extraction of 500 MHz LPR data. The results verify that the low-frequency clutters embedded in the LPR data mainly came from the instrument system of the Yutu rover. Besides, compared with the classic band-pass filter and the mean filter, the CNN filter has better performance when dealing with noise interference and weak signal extraction; compared with Kirchhoff migration, it can provide original high-quality radargram with diffraction information. Based on the high-quality radargram provided by the CNN filter, the subsurface sandwich structure is revealed and the weak signals from three sub-layers within the paleo-regolith are extracted.

For water dynamics investigation in unsaturated (vadose) zones, ground penetrating radar is a popular hydro-geophysical method because it is non-invasive for soil, has high resolution and the results have a direct link with water content. Soil water content and soil hydraulic properties are two key factors for describing the water dynamics in vadose zones. There has been tremendous progress in soil water content and soil hydraulic properties estimation with ground penetrating radar. The purpose of this paper is to provide an overview of the application of ground penetrating radar for soil water dynamics studies. This paper first summarizes various methods for the determination of soil water content. including traditional methods in the surveys of surface ground penetrating radar, borehole ground penetrating radar, and off-ground ground penetrating radar, as well as relatively new methods, such as full waveform inversion, the average envelope amplitude method, and the frequency shift method. This paper further provides a review for estimating soil hydraulic properties with GPR according to the types of ground penetrating radar data. We hope that this review can provide a reference for the application of ground penetrating radar in soil water dynamics studies in the future.

The oral delivery strategy of natural anti-oxidant and anti-inflammatory agents has attracted great attention to improve the effectiveness of ulcerative colitis (UC) treatment. Herein, we developed a novel orally deliverable nanoparticle, carboxymethyl chitosan (CMC)-modified astaxanthin (AXT)-loaded nanoparticles (CMC-AXT-NPs), for UC treatment. The CMC-AXT-NPs were evaluated by appearance, morphology, particle size, ζ-potential, and encapsulation efficiency (EE). The results showed that CMC-AXT-NPs were nearly spherical in shape with a particle size of 34.5 nm and ζ-potential of −30.8 mV, and the EE of CMC-AXT-NPs was as high as 95.03%. The CMC-AXT-NPs exhibited preferable storage stability over time and well-controlled drug-release properties in simulated intestinal fluid. Additionally, in vitro studies revealed that CMC-AXT-NPs remarkably inhibited cytotoxicity induced by LPS and demonstrated superior antioxidant and anti-inflammatory abilities in Raw264.7 cells. Furthermore, CMC-AXT-NPs effectively alleviated clinical symptoms of colitis induced by dextran sulfate sodium salt (DSS), including maintaining body weight, inhibiting colon shortening, and reducing fecal bleeding. Importantly, CMC-AXT-NPs suppressed the expression of pro-inflammatory cytokines like TNF-α, IL-6, and IL-1β and ameliorated DSS-induced oxidative damage. Our results demonstrated the potential of CMC-modified nanoparticles as an oral delivery system and suggested these novel AXT nanoparticles could be a promising strategy for UC treatment.

Intrauterine adhesions (IUA), a leading cause of female infertility, result from a pathological switch in the uterine injury response from regeneration to fibrotic scarring. Current treatments are often inadequate as they fail to address this fundamental shift. Here, we report a “decidualization-empowered” hydrogel that reverses this pathology by synergistically combining a bioactive extracellular matrix from decidualized endometrium (DEndo-UdECM) with the sustained release of the anti-fibrotic peptide Thymosin β4 (Tβ4). In a murine IUA model, a single administration of the hydrogel restores endometrial architecture, resolves fibrosis, and, most critically, leads to a near-complete recovery of fertility. Mechanistically, the hydrogel orchestrates a pro-regenerative niche by reprogramming macrophages to an M2 phenotype while dually inhibiting pyroptosis-driven inflammation and the canonical TGF-β/Smad3 fibrotic cascade. Together, these findings demonstrate that mimicking the biological intelligence of a physiological niche can resolve complex fibrotic diseases and restore organ function. Intrauterine adhesions (IUA) are a leading cause of female infertility. Here, authors engineer a Tβ4-releasing ECM hydrogel that mimics decidualization to promote endometrial regeneration as a therapeutic strategy for treatment of IUA.

Aristolochia contorta Bunge has been widely used as traditional Chinese medicine materials. However, its utility faces a great challenge due to the presence of aristolochic acids (AAs), a class of benzylisoquinoline alkaloid (BIA) derivatives. The first step in BIA skeleton formation is catalysis by norcoclaurine synthase (NCS). To gain knowledge of BIA and AA biosynthesis in A. contorta, genome-wide characterizations of NCS genes were carried out. This resulted in the identification of 15 A. contorta NCSs, namely, AcNCS1–AcNCS15. The AcNCS1–AcNCS8 proteins contained one catalytic domain, whereas the AcNCS9–AcNCS15 proteins had two. Phylogenetic analysis shows that AcNCS proteins can be classified into two clades. Gene expression analysis shows that five AcNCSs, including AcNCS2, AcNCS4, AcNCS5, AcNCS14, and AcNCS15, exhibited relatively high expression in roots and flowers, where norcoclaurine accumulated. An enzyme catalytic activity assay shows that all five of the AcNCSs can catalyze norcoclaurine formation with AcNCS14 and AcNCS15, exhibiting higher catalytic efficiency. Precolumn derivatization analysis shows that the formed norcoclaurine included (S)- and (R)-norcoclaurine, with more (S)-configuration. The results provide useful information for further understanding BIA and AA biosynthesis in A. contorta and for AA elimination and bioactive compound improvement in AA-containing medicinal materials.