Autophagy functions as a cytoprotective mechanism by regulating programmed cell death during desiccation in Syntrichia caninervis.

Desiccation is a state of extreme water loss that is lethal to many plant species. Some desert plants have evolved unique strategies to cope with desiccation stress in their natural environment. Here we present the remarkable stress management mechanism of Syntrichia caninervis, a desert moss species which exhibits an 'A' category of desiccation tolerance. Our research demonstrated that desiccation stress triggers autophagy in S. caninervis while inhibiting Programmed Cell Death (PCD). Silencing of two autophagy-related genes, ATG6 and ATG2, in S. caninervis promoted PCD. Desiccation treatment accelerated cell death in ATG6 and ATG2 gene-silenced S. caninervis. Notably, trehalose was not detected during desiccation, and exogenous application of trehalose cannot activate autophagy. These results suggested that S. caninervis is independent of trehalose accumulation to triggered autophagy. Our results showed that autophagy function as prosurvival mechanism to enhance desiccation tolerance of S. caninervis. Our findings enrich the knowledge of the role of autophagy in plant stress response and may provide new insight into understanding of plant desiccation tolerance.

Target NF-κB p65 for preventing posttraumatic joint contracture in rats.

RelA/p65 is as a crucial component of the nuclear factor κB (NF-κB) signaling pathway that has a significant impact on various fibrotic diseases. However, its role in the fibrosis of tissues surrounding the joint after traumatic injury remains unclear. In this study, rats were divided into three groups: non-operated control (NC) group, p65-siRNA treated (siRNA-p65) group, and negative siRNA treated (siRNA-neg) group. Then, 10 µL (10 nmol) of p65-siRNA was injected into the joint of the siRNA-p65 group. Meanwhile, 10 µL of negative siRNA was administered to the knee joint of the operated siRNA-neg group for comparison. The rats in the NC group did not receive surgery or drug intervention. After 4 weeks of right knee fixation in each group, X-ray measurements revealed significantly reduced degree of knee flexion contracture following p65-siRNA treatment (siRNA-neg: 77.73° ± 2.799°; siRNA-p65: 105.7° ± 2.629°, p < 0.0001). Histopathological examination revealed that the number of dense fibrous connective tissues decreased following p65-siRNA inhibition. Western blot analysis revealed significantly different expression levels of fibrosis-related proteins between the siRNA-p65 and siRNA-neg groups. Immunohistochemical analysis revealed a reduction in the average number of myofibroblasts in the siRNA-p65 group compared with that in the siRNA-neg group. Thus, intra-articular p65-siRNA injection could attenuate fibroblast activation and fibrosis-related protein production, suppress periarticular tissue fibrosis, and prevent joint contracture by downregulating the NF-κB p65 pathway. Statement of clinical significance: Intra-articular injection of p65-siRNA could reduce myofibroblast proliferation and fibrosis-related protein expression by downregulating the NF-κB p65 pathway, inhibit periarticular tissue fibrosis, and prevent joint adhesion, which represents a potential therapy in the prevention of joint fibrosis following traumatic injury.

Shaping the immune-suppressive microenvironment on tumor-associated myeloid cells through tumor-derived exosomes.

Tumor-associated myeloid cells (TAMCs) play a crucial role in orchestrating the dynamics of the tumor immune microenvironment. This heterogeneous population encompasses myeloid-derived suppressor cells, tumor-associated macrophages and dendritic cells, all of which contribute to the establishment of an immunosuppressive milieu that fosters tumor progression. Tumor-derived exosomes (TEXs), small extracellular vesicles secreted by tumor cells, have emerged as central mediators in intercellular communication within the tumor microenvironment. In this comprehensive review, we explore the intricate mechanisms through which TEXs modulate immune-suppressive effects on TAMCs and their profound implications in cancer progression. We delve into the multifaceted ways in which TEXs influence TAMC functions, subsequently affecting tumor immune evasion. Furthermore, we elucidate various therapeutic strategies aimed at targeting TEX-mediated immune suppression, with the ultimate goal of bolstering antitumor immunity.

Dynamics of N6-methyladenosine modification during Alzheimer's disease development.

N6-methyladenosine (m6A) modification is a common RNA modification in the central nervous system and has been linked to various neurological disorders, including Alzheimer's disease (AD). However, the dynamic of mRNA m6A modification and m6A enzymes during the development of AD are not well understood. Therefore, this study examined the expression profiles of m6A and its enzymes in the development of AD. The results showed that changes in the expression levels of m6A regulatory factors occur in the early stages of AD, indicating a potential role for m6A modification in the onset of the disease. Additionally, the analysis of mRNA m6A expression profiles using m6A-seq revealed significant differences in m6A modification between AD and control brains. The genes with differential methylation were found to be enriched in GO and KEGG terms related to processes such as inflammation response, immune system processes. And the differently expressed genes (DEGs) are negatively lryassociated with genes involved in microglia hemostasis, but positively associated with genes related to "disease-associated microglia" (DAM) associated genes. These findings suggest that dysregulation of mRNA m6A modification may contribute to the development of AD by affecting the function and gene expression of microglia.

Attempted replication of pharmacogenetic association of variants in PPP1R14C and CCDC148 with aromatase inhibitor-induced musculoskeletal symptoms.

Third-generation aromatase inhibitors (AI) are the standard treatment for patients with hormone receptor positive (HR+) breast cancer. While effective, AI can lead to severe adverse events, including AI-induced musculoskeletal syndrome (AIMSS). Genetic predictors of AIMSS have the potential to personalize AI treatment and improve outcomes. We attempted to replicate results from a previous genome-wide association study that found a lower risk of AIMSS in patients carrying PPP1R14C rs912571 and a higher risk in patients carrying CCDC148 rs79048288. AIMSS data were collected prospectively from patients with HR+ breast cancer prior to starting and after 3 and 6 months of adjuvant AI via the Patient-Reported Outcome Measurement Information System and Functional Assessment of Cancer Therapy-Endocrine Symptom. Germline genotypes for PPP1R14C rs912571 and CCDC148 rs79048288 were tested for a similar association with AIMSS as previously reported via $2 tests. Of the 143 patients with AIMSS and genetics data were included in the analysis. There was no association identified between PPP1R14C rs912571 and AIMSS risk ( P  > 0.05). Patients carrying CCDC148 rs79048288 variant alleles had lower AIMSS incidence in a secondary analysis ( P  = 0.04); however, this was in the opposite direction of the previous finding. The study did not replicate previously reported associations with AIMSS risk for genetic variants in PPP1R14C and CCDC148 and AIMSS risk. Further research is needed to discover and validate genetic predictors of AIMSS that can be used to personalize treatment in patients with HR+ breast cancer.

Apoptosis dysfunction: unravelling the interplay between ZBP1 activation and viral invasion in innate immune responses.

Apoptosis plays a pivotal role in pathogen elimination and maintaining homeostasis. However, viruses have evolved strategies to evade apoptosis, enabling their persistence within the host. Z-DNA binding protein 1 (ZBP1) is a potent innate immune sensor that detects cytoplasmic nucleic acids and activates the innate immune response to clear pathogens. When apoptosis is inhibited by viral invasion, ZBP1 can be activated to compensate for the effect of apoptosis by triggering an innate immune response. This review examined the mechanisms of apoptosis inhibition and ZBP1 activation during viral invasion. The authors outlined the mechanisms of ZBP1-induced type I interferon, pyroptosis and necroptosis, as well as the crosstalk between ZBP1 and the cGAS-STING signalling pathway. Furthermore, ZBP1 can reverse the suppression of apoptotic signals induced by viruses. Intriguingly, a positive feedback loop exists in the ZBP1 signalling pathway, which intensifies the innate immune response while triggering a cytokine storm, leading to tissue and organ damage. The prudent use of ZBP1, which is a double-edged sword, has significant clinical implications for treating infections and inflammation.

Transcriptome Profiles Reveals ScDREB10 from Syntrichia caninervis Regulated Phenylpropanoid Biosynthesis and Starch/Sucrose Metabolism to Enhance Plant Stress Tolerance.

Desiccation is a kind of extreme form of drought stress and desiccation tolerance (DT) is an ancient trait of plants that allows them to survive tissue water potentials reaching -100 MPa or lower. ScDREB10 is a DREB A-5 transcription factor gene from a DT moss named Syntrichia caninervis, which has strong comprehensive tolerance to osmotic and salt stresses. This study delves further into the molecular mechanism of ScDREB10 stress tolerance based on the transcriptome data of the overexpression of ScDREB10 in Arabidopsis under control, osmotic and salt treatments. The transcriptional analysis of weight gene co-expression network analysis (WGCNA) showed that "phenylpropanoid biosynthesis" and "starch and sucrose metabolism" were key pathways in the network of cyan and yellow modules. Meanwhile, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes (DEGs) also showed that "phenylpropanoid biosynthesis" and "starch and sucrose metabolism" pathways demonstrate the highest enrichment in response to osmotic and salt stress, respectively. Quantitative real-time PCR (qRT-PCR) results confirmed that most genes related to phenylpropanoid biosynthesis" and "starch and sucrose metabolism" pathways in overexpressing ScDREB10 Arabidopsis were up-regulated in response to osmotic and salt stresses, respectively. In line with the results, the corresponding lignin, sucrose, and trehalose contents and sucrose phosphate synthase activities were also increased in overexpressing ScDREB10 Arabidopsis under osmotic and salt stress treatments. Additionally, cis-acting promoter element analyses and yeast one-hybrid experiments showed that ScDREB10 was not only able to bind with classical cis-elements, such as DRE and TATCCC (MYBST1), but also bind with unknown element CGTCCA. All of these findings suggest that ScDREB10 may regulate plant stress tolerance by effecting phenylpropanoid biosynthesis, and starch and sucrose metabolism pathways. This research provides insights into the molecular mechanisms underpinning ScDREB10-mediated stress tolerance and contributes to deeply understanding the A-5 DREB regulatory mechanism.

ROS scavenging enzyme-encoding genes play important roles in the desert moss Syntrichia caninervis response to extreme cold and desiccation stresses.

Abiotic stress is one of the major environmental constraints limiting plant growth. Syntrichia caninervis is one of the unique plant models that can cope with harsh environments. Reactive oxygen species (ROS) are a vital signaling molecule for protecting plants from oxidative stress, but research on ROS in S. caninervis is limited. Here, we identified 112 ROS genes in S. caninervis, including 40 GSTs, 51 PODs, 9 SODs, 6 CATs, 3 GPXs and 3 APXs families. GO and KEGG analyses showed that ROS genes are involved in responses to various stimuli and phenylpropanoid biosynthesis. ROS genes contain many stress-responsive and hormonal cis-elements in their promoter regions. More ROS genes were induced by cold stress than desiccation stress, and both conditions changed the transcript abundances of several ROS genes. CAT and POD, H2O2, MDA, and GSH were also induced under biotic stress, specifically CAT activity. The results indicated that the ScCAT genes and their activities could be strongly associated with the regulation of ROS production. This is the first systematic identification of ROS genes in S. caninervis and our findings contribute to further research into the roles of ScROS adjustment under abiotic stress while also providing excellent genetic resources for plant breeding.

Drying without dying: A genome database for desiccation-tolerant plants and evolution of desiccation tolerance.

Desiccation is typically fatal, but a small number of land plants have evolved vegetative desiccation tolerance (VDT), allowing them to dry without dying through a process called anhydrobiosis. Advances in sequencing technologies have enabled the investigation of genomes for desiccation-tolerant plants over the past decade. However, a dedicated and integrated database for these valuable genomic resources has been lacking. Our prolonged interest in VDT plant genomes motivated us to create the "Drying without Dying" database, which contains a total of 16 VDT-related plant genomes (including 10 mosses) and incorporates 10 genomes that are closely related to VDT plants. The database features bioinformatic tools, such as blast and homologous cluster search, sequence retrieval, Gene Ontology term and metabolic pathway enrichment statistics, expression profiling, co-expression network extraction, and JBrowser exploration for each genome. To demonstrate its utility, we conducted tailored PFAM family statistical analyses, and we discovered that the drought-responsive ABA transporter AWPM-19 family is significantly tandemly duplicated in all bryophytes but rarely so in tracheophytes. Transcriptomic investigations also revealed that response patterns following desiccation diverged between bryophytes and angiosperms. Combined, the analyses provided genomic and transcriptomic evidence supporting a possible divergence and lineage-specific evolution of VDT in plants. The database can be accessed at http://desiccation.novogene.com. We expect this initial release of the "Drying without Dying" plant genome database will facilitate future discovery of VDT genetic resources.

P53 together with ferroptosis: a promising strategy leaving cancer cells without escape.

TP53, functioning as the keeper of the genome, assumes a pivotal function in the inhibition of tumorigenesis. Recent studies have revealed that p53 regulates ferroptosis pathways within tumor cells and is closely related to tumorigenesis. Therefore, we summarize the pathways and mechanisms by which p53 regulates ferroptosis and identify a series of upstream and downstream molecules involved in this process. Furthermore, we construct a p53-ferroptosis network centered on p53. Finally, we present the progress of drugs to prevent wild-type p53 (wtp53) degeneration and restore wtp53, highlighting the deficiencies of drug development and the prospects for p53 in cancer treatment. These findings provide novel strategies and directions for future cancer therapy.

Establishment of an Efficient and Rapid Regeneration System for a Rare Shrubby Desert Legume Eremosparton songoricum.

Eremosparton songoricum (Litv.) Vass. is a rare and extremely drought-tolerant legume shrub that is distributed in Central Asia. E. songoricum naturally grows on bare sand and can tolerate multiple extreme environmental conditions. It is a valuable and important plant resource for desertification prevention and environmental protection, as well as a good material for the exploration of stress tolerance mechanisms and excellent tolerant gene mining. However, the regeneration system for E. songoricum has not yet been established, which markedly limits the conservation and utilization of this endangered and valuable desert legume. Assimilated branches derived from seedlings were cultured on several MS mediums supplemented with various concentrations of TDZ or 6-BA in different combinations with NAA. The results showed that the most efficient multiplication medium was MS medium supplemented with 0.4 mg/L 6-BA and 0.1 mg/L NAA. The most efficient rooting medium was WPM + 25 g/L sucrose. The highest survival rate (77.8%) of transplantation was achieved when the ratio of sand to vermiculite was 1:1. In addition, the optimal callus induction medium was MS + 30 g/L sucrose + 2 mg/L TDZ + 0.5 mg/L NAA in darkness. The E. songoricum callus treated with 100 mM NaCl and 300 mM mannitol on MS medium could be used in proper salt and drought stress treatments in subsequent gene function tests. A rapid and efficient regeneration system for E. songoricum that allowed regeneration within 3 months was developed. The protocol will contribute to the conservation and utilization of this rare and endangered desert stress-tolerant species and also provide a fundamental basis for gene functional analysis in E. songoricum.

Cadmium facilitates the formation of large lipid droplets via PLCß2-DAG-DGKε-PA signal pathway in Leydig cells.

Cadmium (Cd) exposure damages the reproductive system. Lipid droplets (LDs) play an important role in steroid-producing cells to provide raw material for steroid hormone. We have found that the LDs of Leydig cells exposed to Cd are bigger than those of normal cells, but the effects on steroidogenesis and its underlying mechanism remains unclear. Using Isobaric tag for relative and absolute quantitation (iTARQ) proteomics, phosphodiesterase beta-2 (PLCß2) was identified as the most significantly up-regulated protein in immature Leydig cells (ILCs) and adult Leydig cells (ALCs) derived from male rats exposed to maternal Cd. Consistent with high expression of PLCß2, the size of LDs was increased in Leydig cells exposed to Cd, accompanied by reduction in cholesterol and progesterone (P4) levels. However, the high PLCß2 did not result in high diacylglycerol (DAG) level, because Cd exposure up-regulated diacylglycerol kinases ε (DGKε) to promote the conversion from DAG to phosphatidic acid (PA). Exogenous PA, which was consistent with the intracellular PA concentration induced by Cd, facilitated the formation of large LDs in R2C cells, followed by reduced P4 level in the culture medium. When PLCß2 expression was knocked down, the increased DGKε caused by Cd was reversed, and then the PA level was decreased to normal. As results, large LDs returned to normal size, and the level of total cholesterol was improved to restore steroidogenesis. The accumulation of PA regulated by PLCß2-DAG-DGKε signal pathway is responsible for the formation of large LDs and insufficient steroid hormone synthesis in Leydig cells exposed to Cd. These data highlight that LD is an important target organelle for Cd-induced steroid hormone deficiency in males.

Metabolomic Analysis of the Desert Moss Syntrichia caninervis Provides Insights into Plant Dehydration and Rehydration Response.

Desiccation-tolerant (DT) plants can survive extreme dehydration and tolerate the loss of up to 95% of their water content, making them ideal systems to determine the mechanism behind extreme drought stress and identify potential approaches for developing drought-tolerant crops. The desert moss Syntrichia caninervis is an emerging model for extreme desiccation tolerance that has benefited from high-throughput sequencing analyses, allowing identification of stress-tolerant genes; however, its metabolic response to desiccation is unknown. A liquid chromatography-mass spectrometry analysis of S. caninervis at six dehydration-rehydration stages revealed 912 differentially abundant compounds, belonging to 93 metabolic classes. Many (256) metabolites accumulated during rehydration in S. caninervis, whereas only 71 accumulated during the dehydration period, in contrast to the pattern observed in vascular DT plants. During dehydration, nitrogenous amino acids (l-glutamic acid and cysteinylglycine), alkaloids (vinleurosine) and steroids (physalin D) accumulated, whereas glucose 6-phosphate decreased. During rehydration, γ-aminobutyric acid, glucose 6-phosphate and flavonoids (karanjin and aromadendrin) accumulated, as did the plant hormones 12-oxo phytodienoic acid (12-OPDA) and trans-zeatin riboside. The contents ofl-arginine, maltose, turanose, lactulose and sucrose remained high throughout dehydration-rehydration. Syntrichia caninervis thus accumulates antioxidants to scavenge reactive oxygen species, accumulating nitrogenous amino acids and cytoprotective metabolites and decreasing energy metabolism to enter a protective state from dehydration-induced damage. During subsequent rehydration, many metabolites rapidly accumulated to prevent oxidative stress and restore physiological activities while repairing cells, representing a more elaborate rehydration repair mechanism than vascular DT plants, with a faster and greater accumulation of metabolites. This metabolic kinetics analysis in S. caninervis deepens our understanding of its dehydration mechanisms and provides new insights into the different strategies of plant responses to dehydration and rehydration.

Removal of microplastics from water by coagulation of cationic-modified starch: An environmentally friendly solution.

Microplastics (MPs) pose a potential risk to aquatic ecosystems, and there is a growing demand to alleviate the contamination of MPs. Here, we introduce cationic-modified starch (CS) as an eco-friendly bio-coagulant for removing MPs from water. CS with varying degrees of substitution was synthesized and characterized, and its performance in removing MPs was evaluated under different MP sizes, types, and aging, as well as various water conditions. The results indicated that CS efficiently removed MPs, achieving an average removal rate of 65.33 % for polystyrene particles, with higher removal rates for larger, high-density, and aged MPs. The efficiency of CS remained consistent across a wide range of water pH values, but was significantly reduced in the presence of kaolin clay or/and humic acid. The removal efficiency of CS for MPs was enhanced by the non-ionic surfactant, Tween 20, but inhibited by the anionic surfactant, cetyltrimethylammonium bromide. In addition, CS could concurrently remove both MPs and phenanthrene, as a typical water contaminant. Moreover, the applicability of CS was demonstrated in natural water samples from the Ecological Demonstration Zone of the Yangtze River Delta, China, with an average removal rate of 60.13 ± 3.15 %. Taken together, this study offers an environmentally friendly and cost-effective approach for the removal of MPs from water, demonstrating CS has significant application potential as a sustainable solution to mitigate microplastic pollution.

Preparation of Organic-Inorganic Phosphorus-Nitrogen-Based Flame Retardants and Their Application to Plywood.

The combustibility of wood can be improved by physical and chemical means, thus expanding the use of wood products. In this study, two novel phosphorus-nitrogen flame retardants (UCPR and MCPR) were developed, and the intercalated modified layered double hydroxides (LDH) thereof were designated as UCPR-LDH and MCPR-LDH. By impregnating poplar veneer with UCPR-LDH and MCPR-LDH solutions, the study investigated the effects of different concentrations (1%, 5%, 10%), processes (vacuum-pressure impregnation, room temperature impregnation, normal-pressure impregnation), and impregnation times (2 h, 3 h, 24 h, 48 h) on the weight-gain rate of veneer. The optimal process was then selected for preparing formaldehyde-free three-layer plywood. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) were used to characterize the UCPR and MCPR. Meanwhile, gel-permeation chromatography (GPC) demonstrated that the molecular weight of the synthesized flame retardants increased as their molecular distribution became more uniform. The impregnation process was performed at normal temperature and pressure for 48 h at a 5% flame retardant concentration. Results from cone calorimetry indicate that the UCPR-LDH plywood exhibits a peak heat release rate that is 30.43% lower than that of the control group, demonstrating superior thermal barrier performance. The smoke emission of the MCPR-LDH plywood was reduced by 33.62% compared to the control group, indicating superior smoke suppression performance. This method presents a viable approach for synthesizing organic-inorganic flame retardants.

Stochastic momentum methods for non-convex learning without bounded assumptions.

Stochastic momentum methods are widely used to solve stochastic optimization problems in machine learning. However, most of the existing theoretical analyses rely on either bounded assumptions or strong stepsize conditions. In this paper, we focus on a class of non-convex objective functions satisfying the Polyak-Lojasiewicz (PL) condition and present a unified convergence rate analysis for stochastic momentum methods without any bounded assumptions, which covers stochastic heavy ball (SHB) and stochastic Nesterov accelerated gradient (SNAG). Our analysis achieves the more challenging last-iterate convergence rate of function values under the relaxed growth (RG) condition, which is a weaker assumption than those used in related work. Specifically, we attain the sub-linear rate for stochastic momentum methods with diminishing stepsizes, and the linear convergence rate for constant stepsizes if the strong growth (SG) condition holds. We also examine the iteration complexity for obtaining an ϵ-accurate solution of the last-iterate. Moreover, we provide a more flexible stepsize scheme for stochastic momentum methods in three points: (i) relaxing the last-iterate convergence stepsize from square summable to zero limitation; (ii) extending the minimum-iterate convergence rate stepsize to the non-monotonic case; (iii) expanding the last-iterate convergence rate stepsize to a more general form. Finally, we conduct numerical experiments on benchmark datasets to validate our theoretical findings.

Adhesive Ion-Conducting Hydrogel Strain Sensor with High Sensitivity, Long-Term Stability, and Extreme Temperature Tolerance.

Ion-conducting hydrogels with excellent flexibility and ductility have great potential in human movements monitoring. However, some obstacles, including a small detection range, low sensitivity, low electrical conductivity, and poor stability under extreme conditions, impede their use as sensors. Herein, an ion-conducting hydrogel comprising acrylamide (AM), lauryl methacrylate (LMA), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), and a water/glycerol binary solvent (named the AM-LMA-AMPS-LiCl (water/glycerol) hydrogel) is designed, which exhibits an enlarged detection range of 0%-1823% and improved transparency. Notably, the ion channel constructed using AMPS and LiCl significantly improves the sensitivity (gauge factor = 22.15 ± 2.86) of the hydrogel. The water/glycerol binary solvent endows the hydrogel with electrical and mechanical stability under extreme conditions (70 and -80 °C). Furthermore, the AM-LMA-AMPS-LiCl (water/glycerol) hydrogel exhibits antifatigue properties for 10 cycles (0%-1000%) because of noncovalent interactions such as hydrophobic interactions and hydrogen bonding. The hydrogel can be used to monitor human movements such as joint bending and perceive subtle discrepancies such as different joint bending speeds and angles, showing its great potential application in human movement monitoring, electronic skin, and wearable devices.