Search

Background: Glutamine is crucial for the activation and efficacy of T cells, and may play a role in regulating the immune environment. This study aimed to investigate the potential role of glutamine in the activation and proliferation of induced regulatory T cells (iTregs). Methods: CD4+CD45RA1T cells were sorted from peripheral blood mononuclear cells and cultured to analyze iTreg differentiation. Glutamine was then added to the culture system to evaluate the effects of glutamine on iTregs by determining oxidative phosphorylation (OXPHOS), apoptosis, and cytokine secretion. Additionally, a humanized murine graft-versus-host disease (GVHD) model was constructed to confirm the efficacy of glutaminetreated iTregs in vivo. Results: After being cultured in vitro, glutamine significantly enhanced the levels of Foxp3, CTLA-4, CD39, CD69, IL-10, TGF-ß, and Ki67 (CTLA-4, IL-10, TGF-ß are immunosuppressive markers of iTregs) compared with that of the control iTregs (P < 0.05). Furthermore, the growth curve showed that the proliferative ability of glutaminetreated iTregs was better than that of the control iTregs (P < 0.01). Compared with the control iTregs, glutamine supplementation significantly increased oxygen consumption rates and ATP production (P < 0.05), significantly downregulated Annexin V and Caspase 3, and upregulated BCL2 (P < 0.05). However, GPNA significantly reversed the effects of glutamine (P < 0.05). Finally, a xeno-GVHD mouse model was successfully established to confirm that glutamine-treated iTregs increased the mice survival rate, delayed weight loss, and alleviated colon injury. Conclusion: Glutamine supplementation can improve the activity and immunosuppressive action of iTregs, and the possible mechanisms by which this occurs are related to cell proliferation, apoptosis, and OXPHOS. [ABSTRACT FROM AUTHOR]

Polyacrylic acid/sodium alginate-based titanium dioxide (PAA/SA@TiO2) composite hydrogel has the good nitrogen removal properties in the nitrogen-containing wastewaters. Under the optimal adsorption conditions, which include pH 7, temperature 35°C, adsorbent dosage 6 g/L, adsorption equilibrium time 70 min, the adsorption efficiency is 85.56%, 79.46%, and 67.63% when the initial ammonia nitrogen concentrations of 100, 200, and 300 mg/L, respectively, indicating that the hydrogel has good adsorption performance for ammonia nitrogen. The adsorption process conforms to the monolayer adsorption of the Langmuir model, and the adsorption kinetic process belongs to the pseudo-second-order kinetic model of chemical adsorption. The structure of PAA/SA@TiO2 composite hydrogel is stable. The thermogravimetric analysis revealed that its main chain of the composite hydrogel began to break and degrade only at 446°C with thermally decomposed hydroxyl and carboxyl groups. At 800°C, the thermal loss rate was 48%. After 5 cycles of adsorption regeneration, the adsorption efficiency only drops by about 10%. The research results showed that PAA/ SA@TiO2 composite hydrogel had great application prospects in the field of nitrogen-containing wastewater treatment, which provided the theoretical basis and operating parameters for the hydrogel applying in the nitrogen-containing wastewaters treatment. [ABSTRACT FROM AUTHOR]

Urothelial carcinoma with squamous differentiation (UCS) is a common variant of bladder cancer for which treatment outcomes with novel agents are largely unknown. In this retrospective analysis comparing 40 patients with UCS and 120 patients with pure UC, we found inferior outcomes for UCS patients treated with immune checkpoint inhibitors or Enfortumab vedotin. This highlights an important unmet clinical need that should be addressed with further studies. Introduction: Urothelial carcinoma with squamous differentiation (UCS) is associated with increased resistance to chemotherapy, but outcomes associated with newer therapies approved in this space over the last 5 to 10 years are less well defined. We investigated clinical outcomes and molecular profiling of patients with UCS treated with an immune checkpoint inhibitor (ICI) and/or Enfortumab vedotin (EV). Patients and Methods: We undertook a retrospective analysis of UC patients treated with ICI and/or EV. Objective response rate (ORR), progression free survival (PFS) and overall survival (OS) were compared between pure UC (pUC) and UCS using X 2 and log-rank tests, respectively. Prevalence of the most commonly detected somatic alterations were also compared between the 2 histologic subgroups. Results: A total of 160 patients (40 UCS, 120 pUC) were identified for this analysis. Among 151 patients treated with ICI (38 UCS, 113 pUC), UCS patients had a shorter mPFS (1.9 vs. 4.8 months, P < 0.01) and mOS (9.2 vs. 20.7 months, P < 0.01) compared to pUC. Among 37 patients treated with EV (12 UCS, 25 pUC), UCS patients had a lower ORR (17% vs. 70%, P < 0.01) and shorter mPFS (3.4 vs. 15.8 months, P < 0.01). UCS samples were enriched for CDKN2A, CDKN2B, PIK3CA, while pUC samples were enriched for ERBB2 alterations. Conclusion: In this single-center retrospective analysis, patients with UCS had a distinct somatic genomic profile relative to patients with pUC. Patients with UCS also had inferior outcomes to ICIs and EV compared to patients with pUC. [ABSTRACT FROM AUTHOR]

Background: Pr imary ur inary neuroendocr ine neoplasms (U-NENs) are extremely rare thus optimal treatment is unknown. Grading and treatment are typically extrapolated from other primary sites. Since 2010, the clinical landscape for NENs has changed substantially. We performed a retrospective review of U-NENs to assess treatment patterns and oncologic outcomes of patients treated in the recent era of NEN therapy. Patients and Methods: A multicenter retrospective review of patients diagnosed after 2005 and alive after 2010. Time to treatment failure (TTF) was used to evaluate progression and toxicity for systemic therapy. Tumors were categorized as having either well-differentiated neuroendocrine tumor (WDNET) or poorly differentiated neuroendocrine carcinoma (PDNEC) histology. Results: A total of 134 patients from 6 centers were included in our analysis, including 94 (70%) bladder, 32 (24%) kidney, 2 (1.5%) urethra and 4 other ur inary pr imar ies (3.0%). Poor ly-differentiated neuroendocrine carcinoma was more common in bladder (92%) than non-bladder tumors (8%). Median Ki-67 available in bladder primary was 90% (n = 24), kidney 10% (n = 23), ureter 95% (n = 1), urethra 54% (n = 2), and others 90% (n = 3). Patients received a median of 2 therapies (range 0-10). Median time to death was not reached in locoregional WDNETs versus 8.2 years (95% CI, 3.5-noncalculable) in metastatic WDNETs (predominantly renal primary). Median time to death was 3.6 years (95% CI, 2.2-9.2) in locoregional PDNECs versus 1 year (95% CI, 0.8-1.3) in metastatic PDNECs (predominantly bladder primary). Conclusion: This is the most extensive series examining treatment patterns in patients with U-NENs in the recent era of NEN therapy. The apparent inferior survival for bladder NENs is likely due to the preponderance of PDNECs in this group. As predicted, treatments for U-NENs mirrored that of other more common NENs. In our retrospective cohort, we observed that patients with WD-UNETs treated with peptide receptor radionuclide therapy (PRRT) and everolimus suggested potential activity for disease control in WD-UNETs. Prospective studies are needed to assess the activity of new oncology drugs in UNENs. [ABSTRACT FROM AUTHOR]

Background: Muscle-derived stem cells ( MI) SCs ) contribute to the repair of injured muscles . However, the myogenicity of MDSCs generated from patients with Duchenne muscular dystrophy (DMD) relative to healthy individuals remains unclear. Methods: A human DMD model was established using the stem cells prepared from muscle derived from patients with DMD (DMD-hMDSCs). The expression of myogenic lineage-specific markers in MDSCs was examined with immunofluorescence, real-time polymerase chain reaction, and western blotting. Results: It was demonstrated that, compared with cells from healthy subjects, DMD-liMDSCs are primed to selfdifferentiate in growth-inducing medium (GM) and robustly differentiate into myotubes in differentiationinducing medium(DM). This feature was termed 'myogenesis activation," and it was speculated that it contributes to the depletion of myogenic progenitors. Furthermore, MI)SCs consistently express pax7, but the timecourse of this expression does not correlate with the expression of the myogenic lineage-specific markers. Conclusions: The myogenesis activation in DMD-hMDSCs demonstrated in this study may provide novel mechanistic insights into DMD pathogenesis and potential therapies. [ABSTRACT FROM AUTHOR]

Computed tomography angiography (CTA) is very popular because it is characterized by rapidity and accessibility. However, CTA is inferior to digital subtraction angiography (DSA) in the diagnosis of intracranial artery stenosis or occlusion. DSA is an invasive examination, so we optimized the quality of cephalic CTA images. We used 5000 CTA images to train multi-scale residual denoising generative adversarial network (MRDGAN). And then 71 CTA images with intracranial large arterial stenosis were treated by Super-Resolution based on Generative Adversarial Network (SRGAN), Enhanced Super-Resolution based on Generative Adversarial Network (ESRGAN) and post-trained MRDGAN, respectively. Peak signal-to-noise ratio (PSNR) and structural similarity index measurement (SSIM) of the SRGAN, ESRGAN, MRDGAN and original CTA images were measured respectively. The qualities of MRDGAN and original images were visually assessed using a 4-point scale. The diagnostic coherence of digital subtraction angiography (DSA) with MRDGAN and original images was analyzed. The PSNR was significantly higher in the MRDGAN CTA images (35.96 ± 1.51) than in the original (31.51 ± 1.43), SRGAN (25.75 ± 1.18) and ESRGAN (30.36 ± 1.05) CTA images (all P < 0.001). The SSIM was significantly higher in the MRDGAN CTA images (0.95 ± 0.02) than in the SRGAN (0.88 ± 0.03) and ESRGAN (0.90 ± 0.02) CTA images (all P < 0.01). The visual assessment was significantly higher in the MRDGAN CTA images (3.52 ± 0.58) than in the original CTA images (2.39 ± 0.69) (P < 0.05). The diagnostic coherence between MRDGAN and DSA (κ = 0.89) was superior to that between original images and DSA (κ = 0.62). Our MRDGAN can effectively optimize original CTA images and improve its clinical diagnostic value for intracranial large artery stenosis. • SRCTA we proposed, is the first application of super-resolution technology in cephalic CTA images. • SRCTA can generate more high-quality cephalic CTA images than the state-of-the-art models ESRGAN and SRGAN. • SRCTA has excellent diagnostic coherence with DSA in intracranial large artery stenosis or occlusion. [ABSTRACT FROM AUTHOR]

The Al-doped Fe3O4/hydroxyapatite (HAP) nanocomposites prepared in pectin matrix was employed as adsorbent that offers high adsorption capacity for fluoride, magnetic separability and good stability. Powder X-ray diffraction and transmission electron microscopy characterizations were used to determine the structure and morphology of as-prepared samples. The needle-like Al-dopedFe3O4/HAP nanocrystals were coated with pectin molecules, which not only induced the nucleation, but inhibited the further growth of nanocrystals. The results of thermogravimetric analysis and Fourier transform infrared spectra showed that the obtained products are organic--inorganic nanocomposites; and the Al doping in composites increased the amount of hydroxyl groups, which could supply more adsorption sites for fluoride. In bath experiments, the adsorption capacity of Al-doped samples was significantly higher than that of pure HAP due to the high affinity of aluminium toward fluoride. The effect of reaction parameters such as pH, calcination temperature, co-existing anions and Al/Ca molar ratio on the adsorption capacity was also investigated to determine optimum adsorption condition. The Al-doped Fe3O4/HAP nanocrystals exhibited high adsorption rate for fluoride during the first 30 min and reached equilibrium within 80 min. The adsorption kinetics and isotherms were well-fitted by the pseudo-second-order kinetic model and the Freundlich isotherm model, respectively. In addition, the adsorption mechanism of fluoride on Al-doped Fe3O4/HAP nanocomposites was investigated, which can be mainly attributed to electrostatic attraction and ion-exchange. [ABSTRACT FROM AUTHOR]

The heavy metal element chromium in wastewater has great and lasting harm to the environment, it is urgent to control the pollution of Cr(VI) in water. In this work, bagasse was modified by phosphoric acid (PMB), nitric acid (NMB) and oxalic acid (OMB) to adsorb Cr(VI) in wastewater. An orthogonal test was applied to investigate the effects of immersion ratio, immersion temperature, immersion time and acid concentration on the adsorption performance of the adsorbent. The results showed that the adsorption efficiency of the adsorbent was the best under the conditions of immersion ratio of 70:1 [V(mL):m(g)], immersion temperature of 293 K, immersion time of 4 h and acid concentration of 1 mol L–1. The adsorbents were characterized by scanning electron microscopy, Brunauer–Emmett–Teller method and Fourier-transform infrared spectroscopy. The specific surface area, pore volume and structure of PMB, NMB and OMB were different from that of bagasse. In addition, PMB, NMB and OMB had better Cr(VI) adsorption performance than the original bagasse. The adsorption of Cr(VI) by PMB, NMB and OMB were well demonstrated by Langmuir adsorption isotherm and quasi-secondary kinetic equation. All results show that PMB, NMB and OMB can be used to purify Cr(VI) wastewater effectively [ABSTRACT FROM AUTHOR]

The monocular 6D pose estimation of a noncooperative satellite is essential in various on-orbit automatic operations. Nevertheless, the application of this technology still faces challenges, such as heavy model parameters and high latency. In this study, we comprehensively explored the critical components of satellite pose estimation, including landmark description, localisation, and the PnP algorithm, and we introduce a high-precision, real-time, and robust pipeline. Existing methods adopt external convex landmarks, such as 11 landmarks for the SPEED dataset, which are insufficient to describe the geometric structure of the satellite. This study adopted a wireframe-based landmark description, encompassing all visually prominent satellite joints connected directly into the satellite's wireframe model. In addition, unlike most existing methods that rely on heatmap-based landmark localisation, which incurs high computational costs and quantisation errors, we adopt direct coordinate classification for satellite landmark localisation, which is lightweight, fast, and accurate. Experimental results on the SPEED dataset demonstrate that our method outperforms the current state-of-the-art technique, with an accuracy increase of 28% and parameter number decrease of 78%. In particular, our method is very lightweight and robust, and it runs in real-time, making it well-suited for on-orbit real-time satellite pose estimation. • A lightweight monocular satellite pose estimation method is very important for resource-constrained in-orbit platforms. • The three key processes of satellite pose estimation are studied to achieve the balance between accuracy and efficiency. • A High-accuracy, real-time, and robust pipeline for noncooperative satellite pose estimation is proposed. [ABSTRACT FROM AUTHOR]

Armillaria luteo-virens (A. luteo-virens) is a kind of edible fungus mainly exists in Qinghai-Tibet of China, but at present only very few studies focus on the bioactivities of its polysaccharides. This study aimed to purify and characterize the structure features of a novel intracellular polysaccharide (ALP-A) derived from A. luteo-virens and explore its potential anti-tumor and immunomodulatory activities. Through systematic separation and purification, we obtained a homogeneous ALP-A with an average molecular weight of 23693Da. Structural analysis indicated that ALP-A was mainly composed of glucose and mannose with a molar ratio of 6.02:1. The repeating unit of ALP-A was →4) -α-D-Glcp-(1→ backbone with α-Glcp-(1→ and α-Manp-(6→ side chains which branched at O-2 position. The anti-tumor assays in vivo suggested that ALP-A could effectively restrain S180 solid tumor growth, protect immune organs and promote the secretion of cytokines (IL2, IL6 and TNF-α) in serum. Besides, in vitro immunomodulatory assays indicated that ALP-A could improve proliferation, phagocytic capacity and raise the level of NO and cytokines in Raw264.7 cells. These results demonstrate that ALP-A which possess potential antitumor and immunomodulatory abilities can be developed as a new functional food. [Display omitted] • Structural analysis indicated that the repeating unit of ALP-A was →4) -α-D-Glcp-(1→ backbone with α-Glcp-(1→ and α-Manp-(6→ side chains which branched at O-2 position. • The anti-tumor assays in vivo suggested that ALP-A could effectively restrain S180 solid tumor growth, protect immune organs and promote the secretion of cytokines. • In vitro immunomodulatory assays indicated that ALP-A could improve proliferation, phagocytic capacity and raise the level of NO and cytokines in Raw264.7 cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • BFO can protect the liver to maintain mice cholesterol homeostasis. • BFO can balance inflammatory response to protect the blood vessels. • Treatment with BFO inhibited the proliferation of foam cells induced by ox-LDL. • BFO can reduce the risk of the occurrence and development of hypercholesterolemia. Burdock fructooligosaccharide (BFO) is a type of linear inulin extracted from burdock root. In this study, we studied the effect of BFO in hypercholesterolemic mice model and found that BFO could decrease the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and oxidized LDL (ox-LDL). BFO also reduce the hepatocyte damage, improve the antioxidant enzymes activity and regulate genes related to the cholesterol homeostasis in liver. Besides, we found that BFO protected the blood vessels by significantly balancing inflammatory cytokines and alleviating the up-regulation of TLR4/MyD88/NF-κB pathway in aorta. Furthermore, we established a foam cells model induced by ox-LDL in vitro and found that 500 and 1000 μg/mL BFO could effectively inhibit cell proliferation and reduce the production of intracellular lipids and inflammatory cytokines. Therefore, BFO can reduce the risk of hypercholesterolemia by maintaining cholesterol homeostasis, reducing vascular inflammation and alleviating macrophage foaming to prevent its further development into cardiovascular diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • An acidic polysaccharide (RBAPS) was gained from fermented burdock residue mediated by R. nigricans. • The structural characteristics of RBAPS were clarified. • RBAPS promoted cell viability and phagocytosis of macrophages. • RBAPS induced the macrophages polarization and pro-inflammatory cytokines secretion. An acidic heteropolysaccharide (RBAPS) with a relative molecular weight of 140.9 kDa was extracted from Rhizopus nigricans mediated burdock residue fermentation. Structural analysis indicated that RBAPS was mainly composed of Rha, Ara, Gal, GalA, GlcA, Glc and Xyl in a molar ratio of 14.5: 14.3: 30.1: 31.0: 5.5: 0.8: 3.8. The dominant backbone of RBAPS consisted of α-Rha p , α-GalA p , and α-Gal p with the branched chains of β-Gal p and α-Ara f. In macrophage RAW264.7 cells, RBAPS promoted proliferation, enhanced phagocytosis, hindered apoptosis, and promoted cytokines (NO, IL-6, TNF-α, and IL-1β) secretion. RBAPS also promoted M1 macrophage transformation and induced the secretion of NO and IL-6 in differentiated macrophages. The findings suggested that RBAPS has the potential immunomodulatory and anti-tumor effects, giving it application prospect in the health and pharmaceutical fields. [ABSTRACT FROM AUTHOR]

[Display omitted] • SEMA-1 is the first benzoselenazolium-based hemicyanine for G-quadruplex detection. • SEMA-1 has potential to detect nucleolar and mitochondrial G-quadruplexes in cells. • Benzoselenazolium-based hemicyanine is a valuable scaffold for probe design. Benzothiazolium and benzoxazolium are common groups for the construction of hemicyanine dyes; however, their isosteric analogue benzoselenazolium have rarely been studied. Here, we report the development of the first benzoselenazolium-based hemicyanine dye for the selective detection of G-quadruplexes. This molecule, SEMA-1 , was validated as a red-emitting and activatable fluorescent probe whose fluorescence would only be activated in the presence of G-quadruplexes in buffer solution. Consistent with this, SEMA-1 was found to accumulate in nucleoli and could be used to detect the high abundance of nucleolar rDNA and rRNA G-quadruplexes in fixed HeLa cells. On the other hand, due to the retained mitochondrial membrane potential in live HeLa cells, SEMA-1 was captured by mitochondria and had the potential to detect the mitochondrial G-quadruplexes. Collectively, this work demonstrates the value of developing G-quadruplex-specific fluorescent probes from novel benzoselenazolium-based hemicyanine scaffold. [ABSTRACT FROM AUTHOR]

The toxic effects of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) on the marine alga Skeletonema costatum were studied, including the population dynamics, chlorophyll fluorescence characteristics, pigment content, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and morphology. High doses (200–600 μg L−1) of BDE-47 significantly suppressed the population growth of S. costatum , with a 96 h EC 50 value of 293 μg L−1. Photosynthetic parameters (F v / F m , rETR max and Φ PSⅡ) of photosystem II (PSII) were significantly inhibited with increasing BDE-47 concentrations. The chlorophyll c (chl c) concentration was also inhibited by exposure to BDE-47. In contrast, chl a and carotenoid concentrations were elevated after exposure to high concentrations of BDE-47 for 72 and 96 h. The SOD activity was generally higher at concentrations of 100–600 μg L−1 than those of the control when the exposure time was less than 48 h. With increasing time, the SOD activity generally decreased, and significantly higher SOD activity only occurred in the treatment with high doses of BDE-47. High MDA contents occurred after exposure for 96 h in all BDE-47 treatments. With increasing BDE-47 concentrations, drastic deformation of the silicious valve and detachment of the strutted processes were found. In addition, drastic decreases in the BDE-47 concentration in culture medium indicated the bioaccumulation of BDE-47 by S. costatum. Our results revealed multiple responses of S. costatum to BDE-47 exposure, and indicated the potential risk of BDE-47 in the East China Sea based on these responses. • The S. costatum strain from the East China Sea showed limited tolerance to BDE-47. • Parameters of chl a fluorescence were inhibited. • Elevated chl a and carotenoids but decreased chl c concentrations were found. • Lipid peroxidation did not follow the changing patterns of SOD. • Potential risks of BDE-47 in the East China Sea should be highlighted. [ABSTRACT FROM AUTHOR]

Transient receptor potential vanilloid 3 channel (TRPV3) is closely associated with skin inflammation, but there is a lack of effective and specific inhibitors for clinical use. In this study, we identified antimalarial hydroxychloroquine (HCQ) as a selective TRPV3 inhibitor following the prediction by network pharmacology data analysis. In whole-cell patch-clamp recordings, HCQ inhibited the current of the TRPV3 channel, with an IC50 of 51.69 ± 4.78 mM. At the single-channel level, HCQ reduced the open probability of TRPV3 and decreased single-channel conductance. Molecular docking and sitedirected mutagenesis confirmed that residues in the pore domain were critical for the activity of HCQ. In vivo, HCQ effectively reduced carvacrol-induced epidermal thickening, erythema, and desquamation. Additionally, the serum immunoglobulin E and inflammatory factors such as tumor necrosis factor-a and interleukin-6 were markedly decreased in the dorsal skin tissues in the HCQ treatment group, as compared to the model group. Our results suggested the antimalarial HCQ may represent a potential alleviator for treating skin inflammation by inhibiting TRPV3 channels. [ABSTRACT FROM AUTHOR]

Periprosthetic osteolysis and subsequent aseptic loosening are the primary causes of failure following total joint arthroplasty. Wear particle–induced osteogenic impairment is recognized as an important contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress emerging as a pivotal underlying mechanism. Hence, searching for potential therapeutic targets and agents capable of modulating ER stress in osteoblasts is crucial for preventing aseptic loosening. Kaempferol (KAE), a natural flavonol compound, has shown promising osteoprotective effects and anti-ER stress properties in diverse diseases. However, the influence of KAE on ER stress-mediated osteogenic impairment induced by wear particles remains unclear. In this study, we observed that KAE effectively relieved TiAl6V4 particles–induced osteolysis by improving osteogenesis in a mouse calvarial model. Furthermore, we demonstrated that KAE could attenuate ER stress-mediated apoptosis in osteoblasts exposed to TiAl6V4 particles, both in vitro and in vivo. Mechanistically, our results revealed that KAE mitigated ER stress-mediated apoptosis by upregulating the IRE1α–XBP1s pathway while concurrently partially inhibiting the IRE1α-regulated RIDD and JNK activation. Collectively, our findings suggest that KAE is a prospective therapeutic agent for treating wear particle–induced osteolysis and highlight the IRE1α–XBP1s pathway as a potential therapeutic target for preventing aseptic loosening. [ABSTRACT FROM AUTHOR]

Juvenile hormone (JH) acid methyltransferase (JHAMT) is a rate-limiting enzyme that converts JH acids or inactive precursors of JHs to active JHs at the final step of JH biosynthesis in insects and thus presents an excellent target for the development of insect growth regulators or insecticides. However, the three-dimensional properties and catalytic mechanism of this enzyme are not known. Herein, we report the crystal structure of the JHAMT apoenzyme, the three-dimensional holoprotein in binary complex with its cofactor S-adenosyl-L-homocysteine, and the ternary complex with S-adenosyl-L-homocysteine and its substrate methyl farnesoate. These structures reveal the ultrafine definition of the binding patterns for JHAMT with its substrate/cofactor. Comparative structural analyses led to novel findings concerning the structural specificity of the progressive conformational changes required for binding interactions that are induced in the presence of cofactor and substrate. Importantly, structural and biochemical analyses enabled identification of one strictly conserved catalytic Gln/His pair within JHAMTs required for catalysis and further provide a molecular basis for substrate recognition and the catalytic mechanism of JHAMTs. These findings lay the foundation for the mechanistic understanding of JH biosynthesis by JHAMTs and provide a rational framework for the discovery and development of specific JHAMT inhibitors as insect growth regulators or insecticides. [ABSTRACT FROM AUTHOR]

Angiosperms possess a life cycle with an alternation of sporophyte and gametophyte generations, which happens in plant organs like pistils. Rice pistils contain ovules and receive pollen for successful fertilization to produce grains. The cellular expression profile in rice pistils is largely unknown. Here, we show a cell census of rice pistils before fertilization through the use of droplet-based single-nucleus RNA sequencing. The ab initio marker identification validated by in situ hybridization assists with cell-type annotation, revealing cell heterogeneity between ovule- and carpel-originated cells. A comparison of 1N (gametophyte) and 2N (sporophyte) nuclei identifies the developmental path of germ cells in ovules with typical resetting of pluripotency before the sporophyte-gametophyte transition, while trajectory analysis of carpel-originated cells suggests previously neglected features of epidermis specification and style function. These findings gain a systems-level view of cellular differentiation and development of rice pistils before flowering and lay a foundation for understanding female reproductive development in plants. [Display omitted] • A cell census of rice pistils is surveyed through single-nucleus RNA sequencing • Partition analysis identifies ovule- and carpel-originated cells in rice pistils • Female germ cells regain pluripotency before the sporophyte-gametophyte transition • Trajectory analysis shows previously neglected features of carpel-originated cells Pistils contain various cell types to play versatile roles in plant reproductive development, including generating female gametes and facilitating fertilization. Li, Zhang, et al. report the comprehensive single-nucleus sequencing cell census of rice pistils and provide a systems-level view of cellular differentiation and development of the female organ in plants. [ABSTRACT FROM AUTHOR]

The autophagic clearance of mitochondria has been defined as mitophagy, which is triggered by mitochondrial damage and serves as a major pathway for mitochondrial homeostasis and cellular quality control. PINK1 and Parkin-mediated mitophagy is the most extensively studied form of mitophagy, which has been linked to the pathogenesis of neurodegenerative dis-orders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The current paradigm of this particular mitophagy pathway is that the ubiquitination of the outer mitochondrial membrane is the key step to enable the recognition of damaged mitochondria by the core autophagic component autophagosome. However, whether the inner mitochondrial membrane (IMM) is ubiquitinated by Parkin and its contribution to sufficient mitophagy remain unclear. Here, using molecular, cellular, and biochemical approaches, we report that prohibitin 2 (PHB2), an essential IMM receptor for mitophagy, is ubiquitinated by Parkin and thereby gains higher affinity to the autophagosome during mitophagy. Our findings suggest that Parkin directly binds to PHB2 through its RING1 domain and promotes K11- and K33-linked ubiquiti-nation on K142/K200 sites of PHB2, thereby enhancing the interaction between PHB2 and MAP1LC3B/LC3B. Interestingly and importantly, our study allows us to propose a novel model in which IMM protein PHB2 serves as both a receptor and a ubiquitin-mediated base for autophagosome recruitment to ensure efficient mitophagy. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy is a lethal muscle disease, caused by mutations in the gene encoding dystrophin, an actin-binding cytoskeletal protein. Absence of functional dystrophin results in muscle weakness and degeneration, eventually leading to cardiac and respiratory failure. Strategies to replace the missing dystrophin via gene therapy have been intensively pursued. However, the dystrophin gene is too large for current gene therapy approaches. Currently available micro-dystrophin constructs lack the actin-binding domain 2 and show decreased actin-binding affinity in vitro compared to full-length dystrophin. Thus, increasing the actin-binding affinity of micro-dystrophin, using small molecules, could be a beneficial therapeutic approach. Here, we have developed and validated a novel high-throughput screening (HTS) assay to discover small molecules that increase the binding affinity of dystrophin's actin-binding domain 1 (ABD1). We engineered a novel FRET biosensor, consisting of the mClover3, fluorescent protein (donor) attached to the C-terminus of dystrophin ABD1, and Alexa Fluor 568 (acceptor) attached to the C-terminal cysteine of actin. We used this biosensor in small-molecule screening, using a unique high-precision, HTS fluorescence lifetime assay, identifying several compounds from an FDA-approved library that significantly increase the binding between actin and ABD1. This HTS assay establishes feasibility for the discovery of small-molecule modulators of the actin-dystrophin inter-action, with the ultimate goal of developing therapies for muscular dystrophy. [ABSTRACT FROM AUTHOR]

[Display omitted] • Acclimation enhanced resistance of Chlorella vulgaris to sulfamethoxazole toxicity. • Increase of catalase and glutathione reductase was critical tolerant mechanism. • Acclimated C. vulgaris exhibited enhanced removal of sulfamethoxazole. • Biodegradation was the major removal mechanism of sulfamethoxazole by C. vulgaris. This study utilized sulfamethoxazole (SMX) acclimatization to enhance the tolerance and biodegradation capacity of Chlorella vulgaris. Compared to wild C. vulgaris , the growth inhibition and oxidative damage induced by SMX evidently decreased in acclimated C. vulgaris , and meanwhile photosynthetic and antioxidant activities were significantly promoted. The physiological analyses with the aid of principal component analysis revealed the increase of catalase and glutathione reductase activities was the critical tolerant mechanism of acclimated C. vulgaris. As the consequence, the acclimated C. vulgaris exhibited enhanced efficiency and (pseudo-first-order) kinetic rate for removal of SMX. The distribution analysis of residual SMX demonstrated the biodegradation was the major removal mechanism of SMX by C. vulgaris , while bioadsorption and bioaccumulation made pimping contributions. During the degradation process of SMX, nine transformation products (TPs) were identified. Based on the identified TPs, a possible transformation pathway was proposed. [ABSTRACT FROM AUTHOR]

In this study, a novel heterogeneous peracetic acid (PAA)-based advanced oxidation process (AOP), viz cobalt ferrite combined with PAA (CoFe,04/PAA), was used to degrade organic contaminants. The best pH for rhodamine B (RhB) degradation in CoFe2O4/PAA system was at 7, and approximately 95% RhB could be removed within 10 min at this pH. Radical scavenging experiments indicated that organic radicals (i.e., CH)(:00' and CH3C0000) were the dominant reactive species for RhB degradation. The X-ray photoelectron spectroscopy (XPS) analysis for the fresh and used catalysts suggested that the catalytic reaction mainly occurred on the surface of the catalyst. Increasing PAA dosage and CoFe204 dosage could enhance the removal of RhB, while excess COFe204 dosage inhibited its degradation probably due to the clumping effect of magnetic nanoparticies. Five degradation products of RhB by CoFe204/PAA were identified and two degradation pathways of RhB were subsequently proposed, including bond cleavage and hydroxylation. CoFe204 exhibited an excellent stability and reusability, and the removal rate of RhB could maintain at 92.4% after four cycles. Several kinds of organic contaminants were selected to evaluate the applicability of CoFe2OAPAA system, and the results suggested that CoFe204/PAA system exhibited a selectivity for different contaminants. [ABSTRACT FROM AUTHOR]