A dominant negative mutation of GhMYB25-like alters cotton fiber initiation, reducing lint and fuzz.

Cotton (Gossypium hirsutum) fibers, vital natural textile materials, are single-cell trichomes that differentiate from the ovule epidermis. These fibers are categorized as lint (longer fibers useful for spinning) or fuzz (shorter, less useful fibers). Currently, developing cotton varieties with high lint yield but without fuzz remains challenging due to our limited knowledge of the molecular mechanisms underlying fiber initiation. This study presents the identification and characterization of a naturally occurring dominant negative mutation GhMYB25-like_AthapT, which results in a reduced lint and fuzzless phenotype. The GhMYB25-like_AthapT protein exerts its dominant negative effect by suppressing the activity of GhMYB25-like during lint and fuzz initiation. Intriguingly, the negative effect of GhMYB25-like_AthapT could be alleviated by high expression levels of GhMYB25-like. We also uncovered the role of GhMYB25-like in regulating the expression of key genes such as GhPDF2 (PROTODERMAL FACTOR 2), CYCD3; 1 (CYCLIN D3; 1), and PLD (Phospholipase D), establishing its significance as a pivotal transcription factor in fiber initiation. We identified other genes within this regulatory network, expanding our understanding of the determinants of fiber cell fate. These findings offer valuable insights for cotton breeding and contribute to our fundamental understanding of fiber development.

Signaling by the EPFL-ERECTA family coordinates female germline specification through the BZR1 family in Arabidopsis.

In most flowering plants, the female germline is initiated in the subepidermal L2 layer of ovule primordia forming a single megaspore mother cell (MMC). How signaling from the L1 (epidermal) layer could contribute to the gene regulatory network (GRN) restricting MMC formation to a single cell is unclear. We show that EPIDERMAL PATTERNING FACTOR-like (EPFL) peptide ligands are expressed in the L1 layer, together with their ERECTA family (ERf) receptor kinases, to control female germline specification in Arabidopsis thaliana. EPFL-ERf dependent signaling restricts multiple subepidermal cells from acquiring MMC-like cell identity by activating the expression of the major brassinosteroid (BR) receptor kinase BRASSINOSTEROID INSENSITIVE 1 and the BR-responsive transcription factor BRASSINOZOLE RESISTANT 1 (BZR1). Additionally, BZR1 coordinates female germline specification by directly activating the expression of a nucleolar GTP-binding protein, NUCLEOSTEMIN-LIKE 1 (NSN1), which is expressed in early-stage ovules excluding the MMC. Mutants defective in this GRN form multiple MMCs resulting in a strong reduction of seed set. In conclusion, we uncovered a ligand/receptor-like kinase-mediated signaling pathway acting upstream and coordinating BR signaling via NSN1 to restrict MMC differentiation to a single subepidermal cell.

The water lily genome and the early evolution of flowering plants.

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 mesangiosperms1-3. 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.

NADPH mimics the antidepressant effects of exercise in a chronic unpredictable stress rat model.

Exercise is known to be an effective intervention for depression. NADPH has been demonstrated to have neuroprotective effects in our previous studies. This study aimed to investigate if NADPH has antidepressant effects and can mimic the effects of exercise in a chronic unpredictable stress (CUS) rat model. CUS rats underwent an 8-week swimming exercise (30 min/d, 5d/w) or were intraperitoneally administered 4 mg/kg or 8 mg/kg NADPH. The open field test (OFT), sucrose preference test (SPT), novelty-suppressed feeding test (NSFT), and forced swimming test (FST) were used to examine the antidepressant-like behaviors of the rats. Exercise, 4 mg/kg, and 8 mg/kg NADPH similarly reduced anxiety, as demonstrated by the number of fecal pellets. Meanwhile, exercise and 8 mg/kg NADPH significantly increased locomotion activity in the OFT. Exercise, 4 mg/kg, and 8 mg/kg NADPH effectively reversed CUS-induced anhedonia in rats in the SPT. Exercise, 4 mg/kg, and 8 mg/kg NADPH had no impact on appetite of depressed rats; however, 8 mg/kg NADPH increased the rats' exploratory activity in the NSFT. Exercise, 4 mg/kg, and 8 mg/kg NADPH significantly reduced the immobility time of CUS model rats, while exercise and 8 mg/kg NADPH postponed the early CUS-induced "immobility" in the FST. These results demonstrated that NADPH has similar antidepressant-like effects to exercise in CUS-induced depression model rats and is a potential exercise-mimicking antidepressant.

Genome-wide identification and expression analysis of calmodulin and calmodulin-like genes in passion fruit (Passiflora edulis) and their involvement in flower and fruit development.

BACKGROUND: The calmodulin (CaM) and calmodulin-like (CML) proteins play regulatory roles in plant growth and development, responses to biotic and abiotic stresses, and other biological processes. As a popular fruit and ornamental crop, it is important to explore the regulatory mechanism of flower and fruit development of passion fruit. RESULTS: In this study, 32 PeCaM/PeCML genes were identified from passion fruit genome and were divided into 9 groups based on phylogenetic analysis. The structural analysis, including conserved motifs, gene structure and homologous modeling, illustrates that the PeCaM/PeCML in the same subgroup have relative conserved structural features. Collinearity analysis suggested that the expansion of the CaM/CML gene family likely took place mainly by segmental duplication, and the whole genome replication events were closely related with the rapid expansion of the gene group. PeCaM/PeCMLs were potentially required for different floral tissues development. Significantly, PeCML26 had extremely high expression levels during ovule and fruit development compared with other PeCML genes, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. The co-presence of various cis-elements associated with growth and development, hormone responsiveness, and stress responsiveness in the promoter regions of these PeCaM/PeCMLs might contribute to their diverse regulatory roles. Furthermore, PeCaM/PeCMLs were also induced by various abiotic stresses. This work provides a comprehensive understanding of the CaM/CML gene family and valuable clues for future studies on the function and evolution of CaM/CML genes in passion fruit. CONCLUSION: A total of 32 PeCaM/PeCML genes were divided into 9 groups. The PeCaM/PeCML genes showed differential expression patterns in floral tissues at different development stages. It is worth noting that PeCML26, which is highly homologous to AtCaM2, not only interacts with multiple BBR-BPC TFs, but also has high expression levels during ovule and fruit development, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. This research lays the foundation for future investigations and validation of the potential function of PeCaM/PeCML genes in the growth and development of passion fruit.

Stomatal evolution and plant adaptation to future climate.

Global climate change is affecting plant photosynthesis and transpiration processes, as well as increasing weather extremes impacting socio-political and environmental events and decisions for decades to come. One major research challenge in plant biology and ecology is the interaction of photosynthesis with the environment. Stomata control plant gas exchange and their evolution was a crucial innovation that facilitated the earliest land plants to colonize terrestrial environments. Stomata couple homoiohydry, together with cuticles, intercellular gas space, with the endohydric water-conducting system, enabling plants to adapt and diversify across the planet. Plants control stomatal movement in response to environmental change through regulating guard cell turgor mediated by membrane transporters and signaling transduction. However, the origin, evolution, and active control of stomata remain controversial topics. We first review stomatal evolution and diversity, providing fossil and phylogenetic evidence of their origins. We summarize functional evolution of guard cell membrane transporters in the context of climate changes and environmental stresses. Our analyses show that the core signaling elements of stomatal movement are more ancient than stomata, while genes involved in stomatal development co-evolved de novo with the earliest stomata. These results suggest that novel stomatal development-specific genes were acquired during plant evolution, whereas genes regulating stomatal movement, especially cell signaling pathways, were inherited ancestrally and co-opted by dynamic functional differentiation. These two processes reflect the different adaptation strategies during land plant evolution.

Molecular evolution and interaction of 14-3-3 proteins with H+-ATPases in plant abiotic stresses.

Environmental stresses severely affect plant growth and crop productivity. Regulated by 14-3-3 proteins (14-3-3s), H+-ATPases (AHAs) are important proton pumps that can induce diverse secondary transport via channels and co-transporters for the abiotic stress response of plants. Many studies demonstrated the roles of 14-3-3s and AHAs in coordinating the processes of plant growth, phytohormone signaling, and stress responses. However, the molecular evolution of 14-3-3s and AHAs has not been summarized in parallel with evolutionary insights across multiple plant species. Here, we comprehensively review the roles of 14-3-3s and AHAs in cell signaling to enhance plant responses to diverse environmental stresses. We analyzed the molecular evolution of key proteins and functional domains that are associated with 14-3-3s and AHAs in plant growth and hormone signaling. The results revealed evolution, duplication, contraction, and expansion of 14-3-3s and AHAs in green plants. We also discussed the stress-specific expression of those 14-3-3and AHA genes in a eudicotyledon (Arabidopsis thaliana), a monocotyledon (Hordeum vulgare), and a moss (Physcomitrium patens) under abiotic stresses. We propose that 14-3-3s and AHAs respond to abiotic stresses through many important targets and signaling components of phytohormones, which could be promising to improve plant tolerance to single or multiple environmental stresses.

Spatiotemporal control of miR398 biogenesis, via chromatin remodeling and kinase signaling, ensures proper ovule development.

The coordinated development of sporophytic and gametophytic tissues is essential for proper ovule patterning and fertility. However, the mechanisms regulating their integrated development remain poorly understood. Here, we report that the Swi2/Snf2-Related1 (SWR1) chromatin-remodeling complex acts with the ERECTA receptor kinase-signaling pathway to control female gametophyte and integument growth in Arabidopsis thaliana by inhibiting transcription of the microRNA gene MIR398c in early-stage megagametogenesis. Moreover, pri-miR398c is transcribed in the female gametophyte but is then translocated to and processed in the ovule sporophytic tissues. Together, SWR1 and ERECTA also activate ARGONAUTE10 (AGO10) expression in the chalaza; AGO10 sequesters miR398, thereby ensuring the expression of three AGAMOUS-LIKE (AGL) genes (AGL51, AGL52, and AGL78) in the female gametophyte. In the context of sexual organ morphogenesis, these findings suggest that the spatiotemporal control of miRNA biogenesis, resulting from coordination between chromatin remodeling and cell signaling, is essential for proper ovule development in Arabidopsis.

The lncRNA LINC01605 promotes the progression of pancreatic ductal adenocarcinoma by activating the mTOR signaling pathway.

BACKGROUND: This study investigated the molecular mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in the process of tumor growth and liver metastasis of pancreatic ductal adenocarcinoma (PDAC). METHODS: LINC01605 was filtered out with specificity through TCGA datasets (related to DFS) and our RNA-sequencing data of PDAC tissue samples from Renji Hospital. The expression level and clinical relevance of LINC01605 were then verified in clinical cohorts and samples by immunohistochemical staining assay and survival analysis. Loss- and gain-of-function experiments were performed to estimate the regulatory effects of LINC01605 in vitro. RNA-seq of LINC01605-knockdown PDAC cells and subsequent inhibitor-based cellular function, western blotting, immunofluorescence and rescue experiments were conducted to explore the mechanisms by which LINC01605 regulates the behaviors of PDAC tumor cells. Subcutaneous xenograft models and intrasplenic liver metastasis models were employed to study its role in PDAC tumor growth and liver metastasis in vivo. RESULTS: LINC01605 expression is upregulated in both PDAC primary tumor and liver metastasis tissues and correlates with poor clinical prognosis. Loss and gain of function experiments in cells demonstrated that LINC01605 promotes the proliferation and migration of PDAC cells in vitro. In subsequent verification experiments, we found that LINC01605 contributes to PDAC progression through cholesterol metabolism regulation in a LIN28B-interacting manner by activating the mTOR signaling pathway. Furthermore, the animal models showed that LINC01605 facilitates the proliferation and metastatic invasion of PDAC cells in vivo. CONCLUSIONS: Our results indicate that the upregulated lncRNA LINC01605 promotes PDAC tumor cell proliferation and migration by regulating cholesterol metabolism via activation of the mTOR signaling pathway in a LIN28B-interacting manner. These findings provide new insight into the role of LINC01605 in PDAC tumor growth and liver metastasis as well as its value for clinical approaches as a metabolic therapeutic target in PDAC.

Preparation and Decomposition of Spherical CL-20 Composites with Enhanced Laser Absorbance and Decreased Mechanical Sensitivity.

Direct initiation of secondary explosives by a semiconductor laser is highly demanded, but it is challenging to exclude the use of sensitive primers. Most laser-sensitive energetic materials are usually mechanically sensitive. In order to reduce the mechanical sensitivity (MS) of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) while improving laser absorbance in the near-infrared band, spherical CL-20 composites (SCCs) embedded with nano aluminum (Al) powder and graphene-based catalyst (GO-CHZ-Co) were prepared by a spray drying method. These SCCs have been characterized comprehensively in terms of their morphologies, particle size distribution, laser absorbance, thermal decomposition behaviors, MS, and laser ignition properties. Results show that the maximum critical impact energy of SCCs was 3.8 J, which is 2.8 J higher than that of pristine ε-CL-20. The critical friction load was increased by at most 108 N compared to pristine CL-20. The absorbance has also been significantly increased up to almost 70% in the wavelength between 400 and 1400 nm, where the peak absorption is located in the region of 800-900 nm. In addition, the initial decomposition temperature (Ti) of SCCs is lower than that of pure CL-20, especially in the presence of GO-CHZ-Co. The apparent activation energy (Ea) for the decomposition of SCCs was largely dependent on the particle size of Al. Preliminary ignition tests indicate that the SCCs can be ignited successfully by a small-power laser.

Racial and ethnic differences in restarting antiplatelet therapy in patients with primary intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND: There has long been clinical disagreement over the resumption of antiplatelet therapy in patients with primary intracranial hemorrhage (ICH). This meta-analysis aimed to systematically evaluate the efficacy and safety of restarting antiplatelet therapy after ICH among different races and ethnicities. METHODS: All relevant medical studies involving adults with antiplatelet-associated ICH published in PubMed, The Cochrane Library and Chinese National Knowledge Infrastructure from inception to March 2024 were sourced. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects model to assess the strength of association between resumption of antiplatelet therapy and our outcomes.The review was not registered and the review protocol was not prepared. RESULTS: Thirty-five studies were included, with 9758 ICH patients. Subgroup analysis revealed that restarting antiplatelet therapy was associated with a significantly higher risk of recurrence or aggravation of cerebral hemorrhage in Asians[OR = 1.48, 95% CI (1.13-1.94), P = 0.004]; in Caucasians, on the contrary, reinitiation of antiplatelet therapy was not associated with a significantly higher risk of recurrence or aggravation of cerebral hemorrhage [OR = 0.85, 95% CI (0.67-1.06), P = 0.149]. Reinitiation of antiplatelet therapy was associated with a significantly lower risk of cerebral infarction [OR = 0.61, 95% CI (0.39-0.96), P = 0.033]. Restarting antiplatelet therapy after cerebral hemorrhage was not associated with a higher incidence rate of mortality [OR = 0.79, 95% CI (0.57, 1.08), P = 0.138], myocardial infarction [OR = 2.40, 95%CI (0.53,10.79), P = 0.253], hemiparesis [OR = 0.38, 95%CI (0.03,4.81), P = 0.451], neurological deficit [OR = 0.86,95%CI(0.32,2.33),P = 0.766]. CONCLUSION: Reinstitution of antiplatelet therapy after ICH was associated with a lower risk of thromboembolic complications.Resumption of antiplatelet therapy was not associated with a higher incidence of cerebral hemorrhage in Caucasians, but may be associated with a higher risk of cerebral hemorrhage recurrence in Asian populations.

AlphaLISA-Based Immunoassay for Detection of Troponin T in Serum of Patients with Acute Myocardial Infarction.

Survival and prognosis of patients with acute myocardial infarction (AMI) are highly dependent on rapid and accurate diagnosis of myocardial damage. Troponin T is the primary diagnostic biomarker and is widely used in clinical practice. Amplified luminescent proximity homogeneous assay (AlphaLISA) may provide a solution to rapidly detect a small amount of analyte through molecular interactions between special luminescent donor beads and acceptor bead. Here, a double-antibody sandwich assay was introduced into AlphaLISA for rapid detection for early diagnosis of AMI and disease staging evaluation. The performance of the assay was evaluated. The study found that the cTnT assay has a linear range of 48.66 to 20,000 ng/L with a limit of detection of 48.66 ng/L. In addition, the assay showed no cross-reactivity with other classic biomarkers of myocardial infarction and was highly reproducible with intra- and inter-batch coefficients of variation of less than 10%, notably, only 3 min was taken, which is particularly suitable for clinical diagnosis. These results suggest that our method can be conveniently applied in the clinic to determine the severity of the patient's condition.

Ultraviolet Photodissociation Dynamics of the 1-Methylallyl Radical.

The ultraviolet (UV) photodissociation dynamics of the 1-methylallyl (1-MA) radical were studied using the high-n Rydberg atom time-of-flight (HRTOF) technique in the wavelength region of 226-244 nm. The 1-MA radicals were produced by 193 nm photodissociation of the 3-chloro-1-butene and 1-chloro-2-butene precursor. The 1 + 1 REMPI spectrum of 1-MA agrees with the previous UV absorption spectrum in this wavelength region. Quantum chemistry calculations show that the UV absorption is mainly attributed to the 3pz Rydberg state (perpendicular to the allyl plane). The H atom photofragment yield (PFY) spectrum of 1-MA from 3-chloro-1-butene displays a broad peak around 230 nm, while that from 1-chloro-2-butene peaks at ∼236 nm. The translational energy distributions of the H atom loss product channel, P (ET)'s, show a bimodal distribution indicating two dissociation pathways in 1-MA. The major pathway is isotropic in product angular distribution with ß âˆ¼ 0 and has a low fraction of average translational energy in the total excess energy, ⟨fT⟩, in the range of 0.13-0.17; this pathway corresponds to unimolecular dissociation of 1-MA after internal conversion to form 1,3-butadiene + H. The minor pathway is anisotropic with ß âˆ¼ -0.23 and has a large ⟨fT⟩ of ∼0.62-0.72. This fast pathway suggests a direct dissociation of the methyl H atom on a repulsive excited state surface or the repulsive part of the ground state surface to form 1,3-butadiene + H. The fast/slow pathway branching ratio is in the range of 0.03-0.08.

Hemoadsorption and Coagulation Systemic Rebalance in Patients Undergoing Nonelective Cardiac Surgery and Treated with Antithrombotics.

INTRODUCTION: Insufficient withdrawal duration of antithrombotics leads to excessive bleeding after major surgery. We hypothesize that intraoperative hemoadsorption (HA) can reduce postoperative allogeneic transfusion requirements and excessive bleeding events (EBE), without an increase in ischemic/thromboembolic events (ITE) in patients who have taken antithrombotics and undergone nonelective cardiac surgery. METHODS: A total of 460 patients admitted to our hospital from 2018 to 2022 were included in this study and divided into two groups: HA and non-HA. Because of the risk of bias due to differences in antithrombotic type, withdrawal duration, or basic coagulation function, propensity score matching was used for analyses. RESULTS: Out of 154 cases in the HA group, 144 pairs were successfully matched. No HA safety events such as hemolysis, hypotension, or device failure occurred. After matching, the two groups were found to be comparable in preoperative antithrombotic type, withdrawal duration, platelets and coagulation function, and demographic and perioperative characteristics. Although the HA group did not have a reduced incidence of EBE, this group exhibited significant decreases in the transfusion rate and volume, the incidence of ITE, acute kidney injury, and central nervous system injury. CONCLUSIONS: For patients who have undergone nonelective cardiac surgery and taken antithrombotics, HA can simply and safely rebalance the postoperative coagulation system and have associations with reduced transfusion and postoperative ITE.

Predictive model and risk analysis for coronary heart disease in people living with HIV using machine learning.

OBJECTIVE: This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). METHODS: Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. RESULTS: The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814-0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. CONCLUSION: This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.

Social participation classification and activities in association with health outcomes among older adults: Results from a scoping review.

AIMS: The aim of this study is to summarize the characteristics of social participation classification and examine the association between activities and health outcomes among older adults. DESIGN: Scoping review. DATA SOURCES: Eight databases (Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, Embase, ProQuest, Psychological Information Database, PubMed, Scopus and Web of Science) were searched. Reference lists of relevant social participation reviews were also considered. METHODS: This study applied a five-stage methodological framework. A narrative synthesis summarized social participation classification and activities and their associations with health outcomes among older adults (≥65 years) living at home, in the community or in nursing residences. RESULTS: Forty-two articles published between 1975 and 2022 were selected. Four classification criteria of social participation were extracted and summarized from these studies. Based on the depth and breadth of social interactions, this review proposed a four-level classification schema. A lower risk of mortality and less visual impairment were associated with participation in level-one, level-three or level-four activities, whereas less depression, less pain and better cognitive function were linked to participation in level-three or level-four activities. CONCLUSION: Future studies should provide a clear definition, establish classification criteria for participation and properly select activity forms while considering both subjective and objective dimensions. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The results could provide data for designing targeted social participation interventions to improve specific health outcomes among older adults. IMPACT: This review could help researchers examine the role of social participation activities in specific health outcomes. Moreover, a proposed classification of social participation activities would benefit researchers and community nurses in discerning the similarities and differences among activities. REPORTING METHOD: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Extension for Scoping Reviews guideline. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Best practices for managing malodorous and infected wounds in advanced cervical cancer.

This cross-sectional study was conducted to examine the most effective strategies for managing malodorous and infected wounds in patients who have been diagnosed with advanced cervical cancer. The research was conducted in Liupanshui, China. The study specifically examined demographic profiles, wound characteristics and effectiveness of wound management approaches. The study incorporated the heterogeneous sample of 289 participants who fulfilled the inclusion criteria. Data collection was conducted via structured questionnaires and medical record evaluations. Descriptive statistics and statistical analyses, such as regression analysis, were utilized to evaluate demographic attributes, wound profiles and effects of different approaches to wound management. The findings unveiled the heterogeneous demographic composition of patients, encompassing differences in socioeconomic standing, educational attainment and age. A wide range of wound characteristics were observed, as 65.7% of lesions during the acute phase with diameter between 2 and 5 centimetres, while 41.5% of lesions had this range. The most prevalent types of infections were those caused by fungi (48.4%), followed by bacterial infections lacking resistance (38.1%). A moderate degree of odour intensity was prevalent, affecting 45.0% of the cases. With maximal odour reduction of 80%, a mean healing time of 25 days and patient satisfaction rating of 4.5 out of 5, Negative Pressure Wound Therapy demonstrated itself to be the most efficacious treatment method. Additional approaches, such as photodynamic therapy and topical antibiotic therapy, demonstrated significant effectiveness, as evidenced by odour reductions of 70% and 75%, respectively, and patient satisfaction ratings of 4.3 and 4.2. Thus, the study determined challenges associated with management of malodorous and infected lesions among patients with advanced cervical cancer. The results underscored the significance of individualized care approaches, drew attention to efficacious wound management techniques and identified critical determinants that impacted patient recuperation. The findings of this study hold potential for advancing palliative care for individuals diagnosed with advanced cervical cancer.

Comparative analyses of American and Asian lotus genomes reveal insights into petal color, carpel thermogenesis and domestication.

Nelumbo lutea (American lotus), which differs from Nelumbo nucifera (Asian lotus) morphologically, is one of the two remaining species in the basal eudicot family Nelumbonaceae. Here, we assembled the 843-Mb genome of American lotus into eight pseudochromosomes containing 31 382 protein-coding genes. Comparative analyses revealed conserved synteny without large chromosomal rearrangements between the genomes of American and Asian lotus and identified 29 533 structural variants (SVs). Carotenoid and anthocyanin pigments determine the yellow and red petal colors of American and Asian lotus, respectively. The structural genes encoding enzymes of the carotenoid and anthocyanin biosynthesis pathways were conserved between two species but differed in expression. We detected SVs caused by repetitive sequence expansion or contraction among the anthocyanin biosynthesis regulatory MYB genes. Further transient overexpression of candidate NnMYB5 induced anthocyanin accumulation in lotus petals. Alternative oxidase (AOX), uncoupling proteins (UCPs), and sugar metabolism and transportation contributed to carpel thermogenesis. Carpels produce heat with sugars transported from leaves as the main substrates, because there was weak tonoplast sugar transporter (TST) activity, and with SWEETs were highly expressed during thermogenesis. Cell proliferation-related activities were particularly enhanced in the warmer carpels compared with stamens during the cold night before blooming, which suggested that thermogenesis plays an important role in flower protogyny. Population genomic analyses revealed deep divergence between American and Asian lotus, and independent domestication affecting seed, rhizome, and flower traits. Our findings provide a high-quality reference genome of American lotus for exploring the genetic divergence and variation between two species and revealed possible genomic bases for petal color, carpel thermogenesis and domestication in lotus.

Analysis of cuproptosis-related lncRNA signature for predicting prognosis and tumor immune microenvironment in pancreatic cancer.

Pancreatic cancer (PC) is a highly malignant digestive tract tumor, with a dismal 5-year survival rate. Recently, cuproptosis was found to be copper-dependent cell death. This work aims to establish a cuproptosis-related lncRNA signature which could predict the prognosis of PC patients and help clinical decision-making. Firstly, cuproptosis-related lncRNAs were identified in the TCGA-PAAD database. Next, a cuproptosis-related lncRNA signature based on five lncRNAs was established. Besides, the ICGC cohort and our samples from 30 PC patients served as external validation groups to verify the predictive power of the risk signature. Then, the expression of CASC8 was verified in PC samples, scRNA-seq dataset CRA001160, and PC cell lines. The correlation between CASC8 and cuproptosis-related genes was validated by Real-Time PCR. Additionally, the roles of CASC8 in PC progression and immune microenvironment characterization were explored by loss-of-function assay. As showed in the results, the prognosis of patients with higher risk scores was prominently worse than that with lower risk scores. Real-Time PCR and single cell analysis suggested that CASC8 was highly expressed in pancreatic cancer and related to cuproptosis. Additionally, gene inhibition of CASC8 impacted the proliferation, apoptosis and migration of PC cells. Furthermore, CASC8 was demonstrated to impact the expression of CD274 and several chemokines, and serve as a key indicator in tumor immune microenvironment characterization. In conclusion, the cuproptosis-related lncRNA signature could provide valuable indications for the prognosis of PC patients, and CASC8 was a candidate biomarker for not only predicting the progression of PC patients but also their antitumor immune responses.

Tyrosine kinase signaling-independent MET-targeting with CAR-T cells.

BACKGROUND: Recent progress in cancer immunotherapy encourages the expansion of chimeric antigen receptor (CAR) T cell therapy in solid tumors including hepatocellular carcinoma (HCC). Overexpression of MET receptor tyrosine kinase is common in HCC; however, MET inhibitors are effective only when MET is in an active form, making patient stratification difficult. Specific MET-targeting CAR-T cells hold the promise of targeting HCC with MET overexpression regardless of signaling pathway activity. METHODS: MET-specific CARs with CD28ζ or 4-1BBζ as co-stimulation domains were constructed. MET-CAR-T cells derived from healthy subjects (HS) and HCC patients were evaluated for their killing activity and cytokine release against HCC cells with various MET activations in vitro, and for their tumor growth inhibition in orthotopic xenograft models in vivo. RESULTS: MET-CAR.CD28ζ and MET-CAR.4-1BBζ T cells derived from both HS and HCC patients specifically killed MET-positive HCC cells. When stimulated with MET-positive HCC cells in vitro, MET-CAR.CD28ζ T cells demonstrated a higher level of cytokine release and expression of programmed cell death protein 1 (PD-1) than MET-CAR.4-1BBζ T cells. When analyzed in vivo, MET-CAR.CD28ζ T cells more effectively inhibited HCC orthotopic tumor growth in mice when compared to MET-CAR.4-1BBζ T cells. CONCLUSION: We generated and characterized MET-specific CAR-T cells for targeting HCC with MET overexpression regardless of MET activation. Compared with MET-CAR.4-1BBζ, MET-CAR.CD28ζ T cells showed a higher anti-HCC potency but also a higher level of T cell exhaustion. While MET-CAR.CD28ζ is preferred for further development, overcoming the exhaustion of MET-CAR-T cells is necessary to improve their therapeutic efficacy in vivo.