Search Results (88)

Context and objective: Post-amputation pain (PAP) is an umbrella term that includes residual limb pain (RLP) and phantom limb pain (PLP), posing a significant challenge to recovery and quality of life after limb loss. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has gained interest for its potential to manage PAP, particularly in refractory cases. This narrative review explores the efficacy of ketamine for PAP and the emerging role of pharmacogenomics in guiding its use. Methods: A literature review of PubMed, Embase, and Cochrane databases was conducted, focusing on clinical trials, systematic reviews, and genetic influences on ketamine metabolism and response. Studies suggest that perioperative ketamine can reduce PAP severity and opioid use. However, outcomes vary, with some patients experiencing transient relief and others achieving prolonged benefit. Results: This variability may be linked to genetic differences in CYP2B6, CYP3A4/5, COMT Val158Met, SLC6A2, and KCNS1, which affect ketamine’s metabolism, efficacy and side effect profile. Understanding these pharmacogenomic factors could enable more personalized and effective ketamine therapy. Conclusion: Despite its promise, inconsistent dosing regimens and limited integration of genetic data hinder standardization. Further research into genotype-guided ketamine protocols may improve treatment outcomes and support precision analgesia in amputee care. Full article

Introduction: SIMPLR-2 is a follow-up to the international, multicenter SIMPLR-1 study evaluating long-term oncological outcomes after open (OLP), laparoscopic (LLP), and robotic (RLP) left pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). Methods: A retrospective analysis of 71 PDAC patients from three high-volume centers was performed. Surgical approaches were stratified into open, laparoscopic, and robotic. The primary endpoint was overall survival (OS); recurrence-free survival (RFS) was also assessed. Kaplan–Meier and Cox regression analyses were used, including propensity score adjustment. Results: Median OS was 11.0 months for OLP and 24.0 months for minimally invasive approaches (p = 0.169). Median RFS was 6 vs. 15 months, respectively (p = 0.258). No significant differences were found between surgical approaches. Conclusions: Although longer survival was observed in minimally invasive groups, differences were not statistically significant. Larger prospective trials are needed to clarify the long-term oncologic impact of a surgical approach in PDAC. Full article

The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism of action, exerting direct bactericidal and fungicidal effects with minimal risk of resistance development. Although aPDT has shown efficacy against a variety of pathogens, data on its activity against large collections of clinical multidrug-resistant strains are still limited. In this study, we assessed the antimicrobial activity of the photosensitizer RLP068/Cl combined with a red light-emitting LED source at 630 nm (Molteni Farmaceutici, Italy) against a large panel of Gram-negative and Gram-positive bacterial strains harboring relevant resistance traits and Candida species. Our results demonstrated the significant microbicidal activity of RLP068/Cl against all of the tested strains regardless of their resistance phenotype, with particularly prominent activity against Gram-positive bacteria (range of bactericidal concentrations 0.05–0.1 µM), which required significantly lower exposure to photosensitizer compared to Candida and Gram-negative species (range 5–20 µM). Overall, these findings support the potential use of RLP068/Cl-mediated aPDT as an effective therapeutic strategy for the management of localized infections caused by MDR organisms, particularly when conventional therapeutic options are limited. Full article

This study identifies and classifies resistance gene analogues (RGAs) in the genomes of Brassica nigra, Sinapis arvensis and Sinapis alba using the RGAugury pipeline. RGAs were categorised into four main classes: receptor-like kinases (RLKs), receptor-like proteins (RLPs), nucleotide-binding leucine-rich repeat (NLR) proteins and transmembrane-coiled-coil (TM-CC) genes. A total of 4499 candidate RGAs were detected, with species-specific proportions. RLKs were the most abundant across all genomes, followed by TM-CCs and RLPs. The sub-classification of RLKs and RLPs identified LRR-RLKs, LRR-RLPs, LysM-RLKs, and LysM-RLPs. Atypical NLRs were more frequent than typical ones in all species. Atypical NLRs were more frequent than typical ones in all species. We explored the relationship between chromosome size and RGA count using regression analysis. In B. nigra and S. arvensis, larger chromosomes generally harboured more RGAs, while S. alba displayed the opposite trend. Exceptions were observed in all species, where some larger chromosomes contained fewer RGAs in B. nigra and S. arvensis, or more RGAs in S. alba. The distribution and density of RGAs across chromosomes were examined. RGA distribution was skewed towards chromosomal ends, with patterns differing across RGA types. Sequence hierarchical pairwise similarity analysis revealed distinct gene clusters, suggesting evolutionary relationships. The study also identified homologous genes among RGAs and non-RGAs in each species, providing insights into disease resistance mechanisms. Finally, RLKs and RLPs were co-localised with reported disease resistance loci in Brassica, indicating significant associations. Phylogenetic analysis of cloned RGAs and QTL-mapped RLKs and RLPs identified distinct clusters, enhancing our understanding of their evolutionary trajectories. These findings provide a comprehensive view of RGA diversity and genomics in these Brassicaceae species, providing valuable insights for future research in plant disease resistance and crop improvement. Full article

Objective: This study compares the surgical and oncological outcomes of minimally invasive robotic (RLP) and laparoscopic (LLP) left pancreatectomy in pancreatic cancer (PC) patients. Methods: Data from patients who underwent minimally invasive left pancreatectomy between 2013 and 2023 were analyzed. Two groups were identified: RLP and LLP. Perioperative outcomes were compared, including operative time, blood loss, conversion rate, and postoperative complications. Oncological outcomes included margin status, lymph node retrieval, lymph node status, overall survival (OS), and disease-free survival (DFS). Results: Fifty-four patients were divided into the LLP (n = 39) and RLP (n = 15) groups. The median operative time was shorter for LLP than RLP [260 min vs. 366 min, p = 0.007]. Blood loss and conversion rates were comparable (p > 0.05). In the LLP group, significantly more lymph nodes were harvested (29 vs. 19, p = 0.05), and a higher percentage of positive lymph nodes was noted (72% vs. 40%, p = 0.033). No significant difference was found in the R0 resection status (82% vs. 73%, p = 0.358). After a median follow-up of 26 months, OS (23 months vs. 34 months, p = 0.812) and DFS (17 months vs. 16 months, p = 0.635) were similar. Conclusion: RLP provides outcomes identical to LLP in treating body–tail pancreatic cancer, with further studies needed to confirm its long-term oncological efficacy. Full article

Postamputation pain (PAP), including residual limb pain (RLP) and phantom limb pain (PLP), remains a significant and debilitating complication after limb loss. Despite advances in pharmacological management, many patients experience inadequate pain relief, underscoring the need for alternative therapeutic strategies. Objective: This narrative review critically synthesizes current interventional therapies for PAP, focusing on mechanisms, clinical efficacy and practical application. Methods: A literature search was conducted in PubMed, EMBASE, Scopus and Web of Science databases for studies published between 2015 and 2025. Relevant articles on peripheral nerve interventions as well as different neuromodulation techniques were included. Results: Peripheral interventions (such as alcohol neurolysis, radiofrequency ablation (RFA) and cryoneurolysis (CNL)) and neuromodulation techniques (including spinal cord stimulation (SCS), dorsal root ganglion (DRG) stimulation and cauda equina stimulation (CES)) demonstrate promising outcomes for PAP. Peripheral nerve stimulation (PNS) shows favorable safety and efficacy profiles and may help prevent the chronification of pain. Conclusions: Contemporary interventional therapies represent valuable options in the multidisciplinary management of PAP. Nevertheless, further research is required to standardize clinical algorithms, optimize therapeutic decision-making and improve long-term outcomes and quality of life for individuals with PAP. Full article

Rice blast disease is a major threat to rice yields. Sustainable control relies on resistant varieties, where plant immunity is triggered by pattern recognition receptors like receptor-like proteins (RLPs). The rice RLP chitin-elicitor binding protin (CEBiP) recognizes fungal chitin and confers blast resistance to pathogen Magnaporthe oryzae. However, understanding of the broader signaling and metabolomic pathways associated with CEBiP activation remains limited. Here, we performed an integrated transcriptomic and metabolomic analysis of the rice Zhonghua 11 genotype and CEBiP knockout plants. Both plants were infected with M. oryzae, and infected leaves were harvested at 24, 48, and 72 hpi for RNA sequencing and Liquid Chromatography-Tandem Mass Spectrometry analysis. Transcriptomics identified a total of 655 genes that were differentially regulated upon knockout of CEBiP; they were mainly related to diterpenoid/phenylpropanoid biosynthesis, nitrogen metabolism, the mitogen-activated protein kinasesignaling pathway, plant–pathogen interaction, and plant hormone signal transduction. The presence of a large number of pathogenesis-related protein 1 family genes indicates the key role of salicylic acid (SA) in CEBiP immunity. Metabolomics detected a total of 962 differentially accumulated metabolites and highlights the roles of caffeine and glutathione metabolism in CEBiP-mediated immunity. Since caffeine and glutathione metabolism can regulate SA signaling, we propose that SA signaling plays a central role in the CEBiP immune function. Full article

Introduction: Rice, a cornerstone of global food security, faces escalating demands for enhanced yield and disease resistance. We collected 300 high-quality genomes, representing both cultivated (Oryza sativa indica, O. sativa japonica, and O. sativa aus) and wild species (O. rufipogon, O. glaberrima, and O. barthii). Methods: Leveraging HMMER, NLR-Annotator, and OrthoFinder, we systematically identified 148,077 leucine-rich repeat (LRR) and 143,459 nucleotide-binding leucine-rich repeat (NLR) genes, with LRR receptor-like kinases (LRR-RLKs) dominating immune receptor proportions, followed by coiled-coil domain containing (CNL)-type NLRs and LRR receptor-like proteins (LRR-RLPs). Results: Benchmarking Universal Single-Copy Orthologs (BUSCO) assessments confirmed robust genome quality (average score: 94.78). Strikingly, 454 TIR-NB-LRR (TNL) genes—typically rare in monocots—were detected, challenging prior assumptions. Phylogenetic analysis with Arabidopsis TNLs highlighted five O. glaberrima genes clustering with dicot TNLs; these genes featured truncated PLN03210 motifs fused to nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4 (NB-ARC) and LRR domains. Conclusions: By bridging structural genomics, evolutionary dynamics, and domestication-driven adaptation, this work provides a foundation for targeted breeding strategies and advances functional studies of plant immunity in rice. Full article

Brassica napus is one of the most extensively cultivated oilseed crops in China, but its yield is significantly impacted by stem rot caused by Sclerotinia sclerotiorum. Receptor-like proteins (RLPs) and receptor-like kinases (RLKs) play essential roles in plant–pathogen interactions; however, their regulatory mechanisms remain largely unknown in B. napus. In this study, we investigated the function of the leucine-rich repeat receptor-like protein BnaRLP-G13-1 in Brassica napus immunity. Previous observations indicated that B. napus plants expressing BnaRLP-G13-1 exhibited enhanced resistance to Sclerotinia sclerotiorum. We hypothesized that BnaRLP-G13-1 mediates pathogen recognition and immune signaling. To test this, we employed mitogen-activated protein kinase (MAPK) activity assays, transgenic overexpression analyses, and pathogen infection assays. Our results demonstrated that BnaRLP-G13-1 recognizes the conserved necrosis- and ethylene-inducing peptide Ssnlp24_SsNEP2 derived from S. sclerotiorum, triggering MAPK cascades and subsequent immune responses. Furthermore, protein interaction studies revealed that BnaRLP-G13-1 physically interacts with the receptor-like kinase BnaSOBIR1, which is essential for full antifungal defense activation. These results elucidate the molecular basis of BnaRLP-G13-1-mediated immunity, providing insights into improving disease resistance in oilseed crops. Full article

A deeper root system can improve the efficiency of water and nutrient absorption from soil; therefore, genetic improvements to the root length of crops are essential for yield stability under drought stress. We previously identified a stable quantitative trait locus (QTL) qRLP12 for root length under polyethylene glycol (PEG)-induced drought stress in a Jinhuangma (JHM, sensitive)/Zhushanbai (ZSB, tolerant) recombinant inbred line (RIL) population. To validate and fine map this QTL, in this study, a secondary F₂ population was constructed, and the genetic effect of the target QTL was validated by comparing the phenotype data of different genotypes. Using newly developed markers, 14 genotypes of recombinant F₂ individuals were obtained. A phenotypic analysis of homozygous recombinant progeny lines narrowed qRLP12 to a 91 kb region. Seven putative predicted genes were identified in the target region, among which LOC105165547, a callose synthase gene, was the only one containing nonsynonymous variations in the coding region between two parents. Quantitative real-time PCR analysis revealed that LOC105165547 was significantly induced by PEG stress in the qRLP12+ line. These indicated that LOC105165547 might be the candidate gene for qRLP12, which is responsible for root length subjected to PEG stress. Our results provide a favored gene resource for improving root length under drought stress in sesame. Full article

Wheat (Triticum aestivum L.) is a primary crop globally. Among the numerous pathogens affecting wheat production, Puccinia striiformis f. sp. tritici (Pst) is a significant biotic stress agent and poses a major threat to world food security by causing stripe rust or yellow rust disease. Understanding the molecular basis of plant–pathogen interactions is crucial for developing new means of disease management. It is well established that the effector proteins play a pivotal role in pathogenesis. Therefore, studying effector proteins has become an important area of research in plant biology. Our previous work identified differentially expressed candidate secretory effector proteins of stripe rust based on transcriptome sequencing data from susceptible wheat (Avocet S) and resistant wheat (Avocet YR10) infected with Pst. Among the secreted effector proteins, PSTG_14090 contained an ancient double-psi beta-barrel (DPBB) fold, which is conserved in the rare lipoprotein A (RlpA) superfamily. This study investigated the role of PSTG_14090 in plant immune responses, which encodes a protein, here referred to as Pst-DPBB, having 131 amino acids with a predicted signal peptide (SP) of 19 amino acids at the N-terminal end, and the DNA sequence of this effector is highly conserved among different stripe rust races. qRT-PCR analysis indicated that expression levels are upregulated during the early stages of infection. Subcellular localization studies in Nicotiana benthamiana leaves and wheat protoplasts revealed that it is distributed in the cytoplasm, nucleus, and apoplast. We demonstrated that Pst-DPBB negatively regulates the immune response by functioning in various compartments of the plant cells. Based on Co-IP and structural predictions and putative interaction analyses by AlphaFold 3, we propose the probable biological function(s). Pst-DPBB behaves as a papain inhibitor of wheat cysteine protease; Pst-DPBB has high structural homology to kiwellin, which is known to interact with chorismate mutase, suggesting that Pst-DPBB inhibits the native function of the host chorismate mutase involved in salicylic acid synthesis. The DPBB fold is also known to interact with DNA and RNA, which may suggest its possible role in regulating the host gene expression. Full article

Plants utilize plasma membrane localized receptors like kinases (RLKs) or receptor-like proteins (RLPs) to recognize pathogens and activate pattern-triggered immunity (PTI) responses. A gain-of-function mutation in the Arabidopsis RLP SNC2 (SUPPRESSOR OF NPR1-1, CONSTITUTIVE 2) leads to constitutive activation of defense responses in snc2-1D mutant plants. Transcription factors, SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1) and CALMODULIN-BINDING PROTEIN 60g (CBP60g), define two parallel pathways downstream of SNC2. The autoimmunity of snc2-1D was partially affected by single mutations in SARD1 or CBP60g but completely suppressed by the sard1 cbp60g double mutant. From a suppressor screen using sard1-1 snc2-1D, we identified a deubiquitinating enzyme ASSOCIATED MOLECULE WITH THE SH3 DOMAIN OF STAM 1 (AMSH1) as a key component in SNC2-mediated plant immunity. A loss-of-function mutation in AMSH1 can suppress the autoimmune responses of sard1-1 snc2-1D. In eukaryotes, selective protein degradation often occurs through the ubiquitination/deubiquitination system. The deubiquitinating enzymes that remove ubiquitin from target proteins play essential roles in controlling the level of target protein ubiquitination and degradation. As loss of AMSH1 results in decreased BDA1 abundance and BDA1 is a transmembrane protein required for SNC2-mediated immunity, AMSH1 likely contributes to immunity regulation through controlling BDA1 stability. Full article

Greenbug, Schizaphis graminum, is one of the important cereal aphid pests of sorghum in the United States and other parts of the world. Sorghum bicolor variety PI 607900 carries the Schizaphis graminum resistance (SgR1) gene that underlies plant resistance to greenbug biotype I (GBI). Now, the SgR1 has been determined as the major gene conferring greenbug resistance based on the strong association of its presence with the resistance phenotype in sorghum. In this study, we have successfully isolated the SgR1 gene using a map-based cloning approach, and subsequent molecular characterization revealed it encodes a leucine-rich repeat containing receptor-like protein (LRR-RLP). According to DNA sequence analysis, the SgR1 gene are conserved among GBI-resistance sorghum accessions but are variable within susceptible lines. Furthermore, an InDel (−965 nt) at its promoter region and a single-nucleotide polymorphism (SNP, 592 nt) in the CDS of the SgR1 were detected and they are well conserved within resistant genotypes. When the SgR1 gene was cloned and transferred into Arabidopsis plants, the SgR1 was activated in the transgenic Arabidopsis plants in response to attack by green peach aphids according to the results of the histochemical assay, and GUS activity was detected in situ in spots around the vasculature of the leaf where the phloem is located, suggesting its biological function in those transgenic Arabidopsis plants. Overall, this study confirms that the SgR1 gene coding for an LRR-RLP is the major resistance gene to greenbug, a destructive pest in sorghum and wheat. This represents the first greenbug resistance gene cloned so far and indicates that the simple-inherited GBI resistance gene can be used for sorghum improvement with genetic resistance to GBI via molecular breeding or cross-based conventional breeding technologies. Full article

This study explores the performance and flow characteristics of radial labyrinth pumps (RLPs) under various geometrical configurations and operating conditions. Experimental investigations and numerical simulations were conducted to evaluate the impact of design parameters such as blade geometry, channel width and blade angle on pump hydraulic performance. The numerical model, developed using the realizable k-ε turbulence model, was validated with experimental data, achieving satisfactory convergence (4.8%—bladed active disc operating with a smooth passive disc and 3.0%—bladed active disc operating with a bladed passive disc). Analysis of the velocity profiles and vortex structures formed between the active and passive discs was performed. These findings underscore the importance of optimizing disc geometry to balance centrifugal effects and momentum exchange. The obtained head for the model with a bladed active disc operating with a smooth passive disc was H = 24.1 m, while, for the bladed active disc operating with a bladed passive disc, it was almost 1.7 times higher at H = 40.3 m. Additionally, the research identifies potential zones within the pump where energy transfer processes differ, providing insight into targeted design improvements. The findings provide valuable information on the optimization of RLP designs and their broader applicability. Full article

Passion fruit (Passiflora edulis Sims) is a Passifloraceae plant with high economic value. Crown rot caused by Rhizoctonia solani is a major fungal disease, which can seriously reduce the yield and quality of passion fruit. Receptor-like proteins (RLPs), which act as pathogen recognition receptors, are widely involved in plant immune responses and developmental processes. However, the role of RLP family members of passion fruit in resistance to crown rot remains unclear. In this study, evolutionary dynamics analysis and comprehensive genomic characterization of the RLP genes family were performed on passion fruit. A total of 141 PeRLPs in the genome of the ‘Zixiang’ cultivar and 79 PesRLPs in the genome of the ‘Tainong’ cultivar were identified, respectively. Evolutionary analysis showed that proximal and dispersed duplication events were the primary drivers of RLP family expansion. RNA-seq data and RT-qPCR analysis showed that PeRLPs were constitutively expressed in different tissues and induced by low temperature, JA, MeJA, and SA treatments. The PeRLP8 gene was identified as the hub gene by RNA-seq analysis of passion fruit seedlings infected by Rhizoctonia solani. The expression levels of PeRLP8 of the resistant variety Passiflora maliformis (LG) were significantly higher than those of the sensitive variety Passiflora edulis f. flavicarpa (HG). Transient overexpression of PeRLP8 tobacco and passion fruit leaves enhanced the resistance to Rhizoctonia solani, resulting in reduced lesion areas by 52.06% and 54.17%, respectively. In addition, it can increase reactive oxygen species levels and upregulated expression of genes related to active oxygen biosynthesis and JA metabolism in passion fruit leaves. Our research provides new insights into the molecular mechanism and breeding strategy of passion fruit resistance to crown rot. Full article