Poyang Lake, the largest freshwater lake in China, has experienced a large decrease in wetland area due to long-term overutilization and especially after the hydrological drought events from 2003. ...This outdoor study was conducted to elucidate the impacts of drought and high concentrations of N on Vallisneria spinulosa. Compared with the 60 cm water depth, the 30 cm water depth caused no difference except lower leaf weight and greater winter bud number per plant growing in the sediment from Poyang Lake. After 400 mg/L NH
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-N was added to the sediment, the leaf weight, root weight, root length, winter bud number, ramet number and stolon weight of V. spinulosa declined greatly. The high NH
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-N content in sediment increased the influence of low water depth on V. spinulosa expressed as the relatively light fresh weight per winter bud of 0.11 g. The results indicated that both a low water depth in spring and high N concentration impacted V. spinulosa and the high concentration of NH
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-N limited the adaptation of V. spinulosa to the decline in water depths. Thus, besides water-level management, nutrient control is also required to protect and restore aquatic macrophytes in Poyang Lake.
Currently, private data leakage and nonlinear classification are two challenges encountered in big data mining. In particular, few studies focus on these issues in support vector machines (SVMs). In ...this paper, to effectively solve them, we propose a novel framework based on the concepts of differential privacy (DP) and kernel functions. This framework can allocate privacy budgets and add artificial noise to different SVM locations simultaneously, which makes the perturbation process freer and more delicate. In addition, under this framework, we propose three algorithms, DP SVMs that perturb the training data set, perturb the kernel function, and utilize mixed perturbation (DPSVM-TDP, DPSVM-KFP, and DPSVM-MP, respectively), all of which can realize accurate classification while ensuring that the users’ privacy is not violated. Moreover, we conduct privacy analysis on these algorithms and prove that they all satisfy ε,0−DP. Finally, we conduct experiments to evaluate the algorithms in terms of different aspects and compare them with the DPSVM with dual-variable perturbation (DVP) algorithm (DPSVM-DVP) to determine the optimal perturbation method. The results show that DPSVM-KFP can achieve the highest data utility and strictest privacy protection with the shortest running time.
Small cell lung cancer (SCLC) transformation serves as a significant mechanism of resistance to tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) with epidermal growth ...factor receptor (EGFR) mutations. To address this clinical challenge, we conducted a retrospective analysis at Zhejiang University School of Medicine, the First Affiliated Hospital, focusing on patients with EGFR sensitizing mutations.
A total of 1012 cases were included in this retrospective analysis. The cohort primarily consisted of patients with EGFR sensitizing mutations. Biopsy-confirmed small cell transformation was observed in seven patients, accounting for 0.7% of the cases. All patients in this subset were initially diagnosed with stage IV adenocarcinoma (ADC), with four cases classified as poorly differentiated and three as moderately to poorly differentiated ADC. EGFR exon 19 deletions were identified in five of these cases. Next-generation sequencing (NGS) was performed on seven cases, revealing mutations in the tumor protein p53 (TP53) gene in four cases and loss of the retinoblastoma1 (RB1) gene in three cases.
The median duration from the initial diagnosis to small cell transformation was 35.9 months (interquartile range: 12.1-84 months). Following small cell transformation during EGFR inhibition, all patients received etoposide/platinum-based treatment, leading to a median progression-free survival (PFS) of 4.7 months (interquartile range: 2.7-10.1 months). Notably, most patients in this series had poorly differentiated adenocarcinomas at the outset. TP53 mutations and RB1 loss were common genetic alterations observed in patients with small cell transformation in this cohort.
The findings underscore the clinical significance of SCLC transformation as a resistance mechanism to EGFR TKIs in NSCLC with EGFR mutations. The observed genetic alterations, including TP53 mutations and RB1 loss, suggest potential associations with the transformation process and warrant further investigation. Understanding the genetic landscape and clinical outcomes in patients experiencing small cell transformation can contribute to improved strategies for managing resistance in EGFR-mutant NSCLC.
Disuse osteoporosis is characterized by decreased bone mass caused by abnormal mechanical stimulation of bone. Piezo1 is a major mechanosensitive ion channel in bone homeostasis. However, whether ...intervening in the action of Piezo1 can rescue disuse osteoporosis remains unresolved. In this study, a commonly-used hindlimb-unloading model is employed to simulate microgravity. By single-cell RNA sequencing, bone marrow-derived mesenchymal stem cells (BMSCs) are the most downregulated cell cluster, and coincidentally, Piezo1 expression is mostly enriched in those cells, and is substantially downregulated by unloading. Importantly, activation of Piezo1 by systemically-introducing yoda1 mimics the effects of mechanical stimulation and thus ameliorates bone loss under simulated microgravity. Mechanistically, Piezo1 activation promotes the proliferation and osteogenic differentiation of Gli1+ BMSCs by activating the β-catenin and its target gene activating transcription factor 4 (ATF4). Inhibiting β-catenin expression substantially attenuates the effect of yoda1 on bone loss, possibly due to inhibited proliferation and osteogenic differentiation capability of Gli1+ BMSCs mediated by ATF4. Lastly, Piezo1 activation also slightly alleviates the osteoporosis of OVX and aged mice. In conclusion, impaired function of Piezo1 in BMSCs leads to insufficient bone formation especially caused by abnormal mechanical stimuli, and is thus a potential therapeutic target for osteoporosis.
Summary
Salt stress is one of the major environmental factors limiting plant growth and development. Although microtubule (MT) organization is known to be involved in response to salt stress, few ...tubulin genes have been identified that confer salt insensitivity in plants.
In this study, we identified a MT encoding gene, OsTUB1, that increased the survival rate of rice plants under salt stress by stabilizing MT organization and ion transporters. We found that OsTUB1 interacted with Kinesin13A protein, which was essential for OsTUB1‐regulated MT organization under salt stress.
Further molecular evidence revealed that a OsTUB1–Kinesin13A complex protected rice from salt stress by sustaining membrane‐localized Na+ transporter OsHKT1;5, a key regulator of ionic homeostasis.
Our results shed light on the function of tubulin and kinesin in regulating MT organization and stabilizing Na+ transporters and Na+ flux at the plasma membrane in rice. The identification of the OsTUB1–Kinesin13A complex provides novel genes for salt insensitivity rice breeding in areas with high soil salinity.
Soil salinity has negative impacts on food security and sustainable agriculture. Ion homeostasis, osmotic adjustment and reactive oxygen species scavenging are the main approaches utilized by rice to ...resist salt stress. Breeding rice cultivars with high salt tolerance (ST) and yield is a significant challenge due to the lack of elite alleles conferring ST. Here, we report that the elite allele LEA12OR, which encodes a late embryogenesis abundant (LEA) protein from the wild rice Oryza rufipogon Griff., improves osmotic adjustment and increases yield under salt stress. Mechanistically, LEA12OR, as the early regulator of the LEA12OR-OsSAPK10-OsbZIP86-OsNCED3 functional module, maintains the kinase stability of OsSAPK10 under salt stress, thereby conferring ST by promoting abscisic acid biosynthesis and accumulation in rice. The superior allele LEA12OR provides a new avenue for improving ST and yield via the application of LEA12OR in current rice through molecular breeding and genome editing.Soil salinity has negative impacts on food security and sustainable agriculture. Ion homeostasis, osmotic adjustment and reactive oxygen species scavenging are the main approaches utilized by rice to resist salt stress. Breeding rice cultivars with high salt tolerance (ST) and yield is a significant challenge due to the lack of elite alleles conferring ST. Here, we report that the elite allele LEA12OR, which encodes a late embryogenesis abundant (LEA) protein from the wild rice Oryza rufipogon Griff., improves osmotic adjustment and increases yield under salt stress. Mechanistically, LEA12OR, as the early regulator of the LEA12OR-OsSAPK10-OsbZIP86-OsNCED3 functional module, maintains the kinase stability of OsSAPK10 under salt stress, thereby conferring ST by promoting abscisic acid biosynthesis and accumulation in rice. The superior allele LEA12OR provides a new avenue for improving ST and yield via the application of LEA12OR in current rice through molecular breeding and genome editing.
Summary Soil salinity has negative impacts on food security and sustainable agriculture. Ion homeostasis, osmotic adjustment and reactive oxygen species scavenging are the main approaches utilized by ...rice to resist salt stress. Breeding rice cultivars with high salt tolerance (ST) and yield is a significant challenge due to the lack of elite alleles conferring ST. Here, we report that the elite allele LEA12 OR , which encodes a late embryogenesis abundant (LEA) protein from the wild rice Oryza rufipogon Griff., improves osmotic adjustment and increases yield under salt stress. Mechanistically, LEA12 OR , as the early regulator of the LEA12 OR ‐ OsSAPK10 ‐ OsbZIP86 ‐ OsNCED3 functional module, maintains the kinase stability of OsSAPK10 under salt stress, thereby conferring ST by promoting abscisic acid biosynthesis and accumulation in rice. The superior allele LEA12 OR provides a new avenue for improving ST and yield via the application of LEA12 OR in current rice through molecular breeding and genome editing.
Stress granules (SGs), membrane-less cellular organelles formed via liquid-liquid phase separation, are central to how cells adapt to various stress conditions, including endoplasmic reticulum ...stress, nutrient scarcity, and hypoxia. Recent studies have underscored a significant link between SGs and the process of tumorigenesis, highlighting that proteins, associated components, and signaling pathways that facilitate SG formation are often upregulated in cancer. SGs play a key role in enhancing tumor cell proliferation, invasion, and migration, while also inhibiting apoptosis, facilitating immune evasion, and driving metabolic reprogramming through multiple mechanisms. Furthermore, SGs have been identified as crucial elements in the development of resistance against chemotherapy, immunotherapy, and radiotherapy across a variety of cancer types. This review delves into the complex role of SGs in cancer development and resistance, bringing together the latest progress in the field and exploring new avenues for therapeutic intervention.
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Cell biology; Cancer
Mitigation of harmful cyanobacterial blooms that constitute a serious threat to water quality, particularly in eutrophic water, such as in aquaculture, is essential. Thus, in this study, we tested ...the efficacy of selected cyanocides towards bloom control in laboratory and outdoor mesocosm experiments. Specifically, we focused on the applicability of a group of cationic disinfectants, alkyltrimethyl ammonium (ATMA) compounds and H2O2. The biocidal effect of four ATMA cations with different alkyl chain lengths was evaluated ex situ using Microcystis colonies collected from a fish pond. The most effective compound, octadecyl trimethyl ammonium (ODTMA), was further evaluated for its selectivity towards 24 cyanobacteria and eukaryotic algae species, including Cyanobacteria, Chlorophyta, Bacillariophyta, Euglenozoa and Cryptophyta. The results indicated selective inhibition of cyanobacteria by ODTMA-Br (C18) on both Chroccocales and Nostocales, but a minor effect on Chlorophytes and Bacillariophytes. The efficacy of ODTMA-Br (C18) (6.4 μM) in mitigating the Microcystis population was compared with that of a single low dose of H2O2 treatments (117.6 μM). ODTMA-Br (C18) suppressed the regrowth of Microcystis for a longer duration than did H2O2. The results suggested that ODTMA-Br (C18) may be used as an effective cyanocide and that it is worth further evaluating this group of cationic compounds as a treatment to mitigate cyanobacterial blooms in aquaculture.
Polychlorinated biphenyls (PCBs) are durable and widely distributed environmental contaminants that can compromise the normal functions of multiple organs and systems; one important mechanism is the ...induction of inflammatory disorders. In this study, we explored the influences of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on inflammatory responses and its underlying mechanisms in the thyroid. Wistar rats were administered PCB118 intraperitoneally at 0, 10, 100, and 1000 μg/kg/d, 5 days a week for 13 weeks; rat thyroid FRTL-5 cells were treated with PCB118 (0, 0.25, 2.5, and 25 nM) for indicated time. Results revealed that PCB118 promoted the generation of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) in a time- and dose-related manner and decreased sodium/iodide symporter (NIS) protein expression. Moreover, stimulation with PCB118 resulted in the upregulation of the aryl hydrocarbon receptor (AhR)-responsive gene cytochrome P450 1A1 in FRTL-5 cells; whereas pretreatment with the AhR inhibitor α-naphthoflavone or AhR small interfering RNA (siRNA) suppressed AhR, CYP1A1, IL-6, and ICAM-1 and restored NIS expression. In vivo and in vitro studies also suggested that the c-Jun N-terminal kinase (JNK) pathway was activated on PCB118 exposure, and the experiments using siRNA for JNK partially blocked PCB118-induced upregulation of IL-6 and ICAM-1 and downregulation of NIS. Altogether, PCB118 stimulates production of IL-6, TNF-α, and ICAM-1 in the thyroid through AhR and JNK activations and subsequently interferes with NIS expression, resulting in the disruption of thyroid structure and function.
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