Search Results (17,896)

Cancer is a complex and evolutionary disease, with the development of different types of cancers leading to various different defective gene mutations. Synthetic lethality is a genetic-level precision medical strategy. Currently, treating BRCA (BReast CAncer)-mutated breast or ovarian cancer cells with a chemical inhibitor (Poly(ADP-ribose) polymerase, PARPi) is a typical synthetic lethal application in clinical practice. However, PARPi therapy has been found to cause off-target effects and therapy-induced immune escape driven by PD-L1 upregulation, allowing for cancer cells to escape attack from the immune response. To overcome these challenges, we developed a core–shell structure comprising a hydrophobic core of quercetin (Q)-mediated PARP inhibition and iron oxide nanoparticles (IONPs), enveloped by a hydrophilic fucoidan (Fu) shell to encapsulate short hairpin RNA targeting Programmed Death Ligand 1 (shPD-L1) for efficient gene transfection (shPD-L1@QIO@Fu). Structurally, the incorporation of quercetin into the intermediate hydrophobic layer enables modulate of the PARP effect, while the inner aqueous core with shPD-L1 gene silencing can inhibit the expression of PD-L1 protein. In this study, we proved that shPD-L1@QIO@Fu demonstrated a dual therapeutic mechanism against BRCA-mutant cancer cells by inducing extensive DNA double-strand breaks and promoting apoptosis. Furthermore, the combined action of quercetin-mediated DNA damage and shPD-L1-driven PD-L1 suppression led to a significant reduction in PD-L1 mRNA to approximately 5% at 72 h and decreased surface PD-L1 below baseline by 96 h. This effectively suppresses PARPi-induced PD-L1 upregulation and enhances antitumor immunity. These findings demonstrate the therapeutic efficacy of shPD-L1@QIO@Fu nanomedicine, providing a promising foundation for advanced co-delivery strategies to synergize PARP inhibition mediated synthetic lethality with immune checkpoint blockade in next-generation precision medicine. Full article

Cannabis sativa L. is a multipurpose crop of increasing agricultural and medical relevance, whose productivity and phytocannabinoid profile are influenced not only by genotype and environmental factors but also by the composition of its microbiota. This review synthesizes current knowledge (2020–2026) on the rhizosphere and endophytic microbiota of hemp, with particular emphasis on plant growth-promoting bacteria (PGPB) and their mechanisms of action. Molecular studies indicate that hemp-associated bacterial communities are dominated by Proteobacteria, Actinobacteriota, Firmicutes and Bacteroidota, with genotype-, tissue- and developmental-stage-dependent variation. PGPB influence plant performance through direct mechanisms, including biological nitrogen fixation, phosphate solubilization, siderophore production and phytohormone synthesis (indole-3-acetic acid (IAA), gibberellins, cytokinins, and 1-aminocyclopropane-1-carboxylate (ACC) deaminase), as well as indirect mechanisms such as antibiosis, enzyme-mediated pathogen inhibition and induction of systemic tolerance to abiotic stress. Experimental studies demonstrate that inoculation with selected strains or consortia can enhance biomass accumulation, improve germination and root architecture, increase resistance to Fusarium oxysporum and modulate cannabinoid and terpene profiles. Importantly, plant responses are cultivar-specific, highlighting the need for genotype-tailored microbial formulations. Full article

Schistosomiasis remains one of the most significant neglected tropical diseases (NTDs) worldwide, sustained by the complex biology of Schistosoma species and the host’s immunopathological responses to tissue-trapped eggs. Despite decades of reliance on praziquantel (PZQ) as the sole chemotherapeutic option, major limitations persist, including its lack of activity against juvenile worms, incomplete protection against reinfection, and concerns regarding emerging tolerance. These challenges, together with persistent hotspots of transmission and uneven global progress toward disease elimination, underscore the urgent need for alternative or complementary therapies. Plant-derived terpenes have emerged as promising antischistosomal candidates due to their structural diversity, broad-spectrum bioactivity, and favourable safety profiles. Evidence from in vitro and in vivo studies demonstrates that monoterpenes, sesquiterpenes, diterpenes, triterpenes, and triterpenoid saponins exert multimodal effects on Schistosoma, including tegumental disruption, interference with metabolic and redox pathways, inhibition of oviposition, and modulation of host immune and fibrotic responses. Advances in mechanistic studies, supported by omics and computational approaches, further highlight their potential as leads for drug development. Additionally, nano-enabled delivery systems offer strategies to overcome pharmacokinetic limitations and enhance therapeutic performance. This review integrates current knowledge on schistosome biology, treatment challenges, and the growing evidence supporting terpenoids as viable components of a diversified antischistosomal therapeutic arsenal. Full article

Background/Objectives: Management of cervical esophageal cancer after induction therapy remains unsettled. Definitive chemoradiotherapy is the guideline default, but a subset of patients with residual but resectable disease may still benefit from surgery. No validated multidisciplinary selection framework exists for this subsite. Methods: We conducted a systematic review registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261369102) and guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, using searches of PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library from inception through 14 April 2026. We identified 1779 records, removed 873 duplicates, and screened 906 records; 87 full-text reports were assessed, of which 67 were excluded at the full-text stage (66 on population grounds—disease not cervical esophageal; and 1 because cervical-direct outcomes were not separable within a mixed cervical/thoracic cohort), leaving 20 cervical-direct studies included in the primary synthesis. Thoracic and meta-analytic sources are cited for indirect comparison and biological rationale but are not counted in the included set. Included studies were evaluated using the Newcastle–Ottawa Scale (NOS) and Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I); certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. Formal meta-analysis was not performed because study design, treatment approach, and outcome reporting were too heterogeneous. Results: Cervical-specific evidence is predominantly retrospective but consistent in direction. Available cervical-specific observational data suggest benefit mainly in patients with biopsy-confirmed incomplete response, resectable residual disease, preserved performance status, and access to experienced centers. Larynx-preserving resection is feasible in 90% of T1–2 tumors and 54% of T3–4 responders. In thoracic esophageal squamous cell carcinoma, neoadjuvant chemoimmunotherapy yields pathologic complete response rates of approximately 29–48%; in cervical disease, the SCENIC trial has reported interim clinical response of approximately 50% in 28 patients, but pathology-confirmed response is not yet available. We present a proposed multidisciplinary selection framework integrating response depth, post-induction stage, laryngeal preservation feasibility, sarcopenia, circulating tumor DNA dynamics, and programmed death-ligand 1 (PD-L1) expression. The framework has not been prospectively validated and is presented as a hypothesis-generating, conceptual tool for multidisciplinary discussion rather than a clinically validated instrument. Adjuvant nivolumab is recommended for residual pathologic disease after margin-negative (R0) resection when surgery follows preoperative chemoradiotherapy; after PD-1-based induction, adjuvant checkpoint inhibition remains investigational. Conclusions: The available cervical-direct evidence is predominantly retrospective and selection-prone, and several inputs supporting the framework are extrapolated from thoracic ESCC cohorts; conclusions about the survival benefit of surgery should therefore be read as associations rather than causal claims. Surgery has a role after induction therapy in carefully selected incomplete responders. The proposed framework is designed for multidisciplinary use and requires prospective validation before routine clinical application. Full article

Neuroinflammation is increasingly implicated in depression pathogenesis, yet the underlying mechanisms are still unclear. This study explores whether PSMB4/MHC-I signaling in the cerebrospinal fluid (CSF)-contacting nucleus mediates neuroinflammatory depression. A persistent neuroinflammation-associated depression model was established in mice by repeated intracerebroventricular lipopolysaccharide (LPS) administration. Depressive-like behaviors were evaluated using established assays. Neuroinflammatory responses and target protein expression were assessed by immunofluorescence, Western blotting, RT-qPCR, and laser capture microdissection. Neuronal activity was mapped by c-Fos staining and manipulated using chemogenetics, alongside pharmacological and genetic interventions. Repeated LPS administration induced significant depressive-like behaviors and obvious neuroinflammation in the CSF-contacting nucleus. Under these conditions, neuronal activity in this nucleus was selectively enhanced. Crucially, chemogenetic activation of these neurons alleviated depressive phenotypes, whereas their inhibition induced depression. Molecularly, LPS significantly upregulated PSMB4 and MHC-I expression. Pharmacological suppression of upstream neuroinflammation reversed this PSMB4 upregulation, and targeted PSMB4 knockdown reduced MHC-I expression, ultimately ameliorating depressive-like behaviors. These findings identify the CSF-contacting nucleus as a critical node in neuroinflammation-induced depression and reveal a novel PSMB4/MHC-I signaling axis linking central inflammatory responses to behavioral deficits. Full article

Alveolar echinococcosis is a life-threatening zoonotic parasitic disease caused by infection of Echinococcus multilocularis larvae. To survive within the host’s immune milieu, E. multilocularis has evolved sophisticated immune evasion strategies, including the expression of immunomodulatory proteins that regulate the host immune response. Our previous studies have demonstrated that E. multilocularis calreticulin (EmCRT) possessed strong binding ability to human complement component C1q to inhibit C1q-initiated complement activation and biological functions. To further elucidate the mechanism by which EmCRT mediates C1q inactivation and immune evasion, the precise C1q-binding site on EmCRT was identified and analyzed in this study through expression of overlapping fragments and synthesis of overlapping peptides covering the identified functional fragment. The fragment expression and functional assay narrowed down the C1q-binding site to the EmCRT-S1 fragment located between amino acids 140 and 204 of EmCRT. The precise binding site was further pinpointed to the P5 peptide (EmCRT160–174 aa) by testing the synthetic peptides covering this region. The binding of peptide P5 to C1q markedly suppressed the activation of the C1q-mediated classical complement pathway and C1q-induced neutrophil chemotaxis, production of reactive oxygen species, cathepsin G, and myeloperoxidase. These findings suggest that the C1q-binding P5 peptide of EmCRT may serve as a potential target for the development of vaccines against echinococcosis or therapeutic drugs for complement-associated inflammatory or autoimmune diseases. Full article

This study evaluates volatile extracts (HE1 and HE2) from the lichen Pseudevernia furfuracea as eco-friendly agents to control algal proliferation, specifically targeting the cyanobacterium Microcystis aeruginosa and the green microalga Chlorella sorokiniana. Both extracts exhibited potent anti-microalgal activity against the two species with a minimum inhibitory concentration (MIC) ranging from 375 to 750 µg/mL. Furthermore, both extracts reduced cell density by more than 98% after eight days of treatment. Chlorophyll a and protein levels decreased significantly (>80%) in both species, indicating suppression of pigment synthesis. However, their physiological responses were distinct: M. aeruginosa underwent early acute oxidative stress and severe membrane damage, while C. sorokiniana exhibited delayed oxidative activation and a negative growth rate, suggesting non-lytic metabolic inhibition. An in silico study by molecular docking of the most abundant compounds identified in these volatile extracts, such as terpenoids (abietatriene, δ-cadinene) and a phenolic compound (atraric acid), showed that these compounds interact with vital cellular targets in M. aeruginosa and C. sorokiniana and likely contribute to the effects observed in these two species. Predictive toxicity by applying the ADMET framework confirmed the favorable bioavailability and low acute toxicity of these volatile compounds. Therefore, P. furfuracea volatiles are promising, species-specific, and environmentally safe candidates for mitigating aquatic algal proliferation through targeted oxidative and metabolic interference. Full article

Background/Objectives: Multiple sclerosis (MS) constitutes a chronic autoimmune, inflammatory, and neurodegenerative disease, with dissemination in space and time, warranting diagnosis. Epstein–Barr virus (EBV) is increasingly recognized as a key contributor to MS pathogenesis. This review summarizes evidence on EBV-related mechanisms of currently approved disease-modifying therapies (DMTs) and emerging EBV-directed therapeutic strategies in MS. Methods: A systematic search of PubMed, Embase, Cochrane, and Web of Science was performed. Original English-language studies addressing EBV-related therapeutic mechanisms or EBV-targeted interventions in MS were included; 23 studies met the inclusion criteria. Results: Current DMTs may influence EBV-related immunity through diverse mechanisms, including modulation of B-cell subsets, altered lymphocyte trafficking, reduction in EBV-specific humoral responses, and restoration of T-cell surveillance. Monoclonal antibody-based therapies, particularly anti-CD20 agents and natalizumab, appear to affect the EBV–B-cell–immune axis through distinct but complementary mechanisms. Other interventions, including interferons, glatiramer acetate, dimethyl fumarate, autologous hematopoietic stem cell transplantation, and vitamin D supplementation, may also modulate EBV-specific cellular or humoral responses, although the magnitude and durability of these effects vary. Emerging EBV-directed approaches, including EBV-specific T-cell therapy, inhibition of specific proteins, modulation of autophagy, and cholesterol-dependent viral latency, provide additional support for targeting EBV-related pathways in MS. Conclusions: The therapeutic efficacy of DMTs in MS may extend beyond nonspecific immunomodulation and involve partial disruption of EBV-driven immune persistence. Further controlled studies are required to validate EBV-related biomarkers and determine whether direct EBV-targeted therapies can provide sustained clinical benefit. Full article

Myalgic Encephalomyelitis (ME) is a chronic, multisystem disease characterized by systemic metabolic dysfunction and post-exertional malaise (PEM). In this study, we investigated the dysregulation of irisin, an exercise-induced myokine, and its potential antagonism by thrombospondin-1 (TSP-1). In a cross-sectional study (92 ME patients vs. 44 sedentary healthy controls), plasma irisin and TSP-1 levels were measured at baseline and after a 90 min mechanical stress challenge applied to induce PEM. ME patients exhibited significantly lower baseline irisin (p < 0.05) and a blunted exertional response (p < 0.05). Paradoxically, baseline irisin was an independent predictor of fatigue severity (β = 0.728, p = 0.018), with moderate-to-severe patients showing elevated levels of both irisin and TSP-1 (p < 0.05), suggesting a compensatory but ineffective response. Functional cellular dielectric spectroscopy indicated that TSP-1 inhibits irisin signaling in a concentration-dependent manner. Irisin signaling was markedly reduced by both αvβ5 blockade and HSP90α inhibition in this experimental system, consistent with a diminished ability to counteract TSP-1. Collectively, these findings support a model in which dysregulation of the irisin–TSP-1 axis contributes to metabolic dysfunction in ME. Elevated circulating TSP-1 levels are associated with symptom severity and are linked to impaired irisin signaling in an HSP90α- and αvβ5-dependent context. This interaction is consistent with defective metabolic adaptation and highlights a potential therapeutic target that warrants further validation to restore energy homeostasis. Full article

Background/Objectives: This study aimed to develop a novel tumor-associated macrophage (TAM)-targeting nanoplatform to improve the solubility and bioavailability of camptothecin (CPT) and achieve active targeted drug delivery for enhanced anti-tumor immunotherapy. Methods: We constructed a sialic acid-disulfide bond-camptothecin (SA-SS-CPT) nanowire system. Sialic acid was used as a targeting ligand to specifically recognize the overexpressed Siglec-E receptor on TAMs. Upon cellular internalization, the disulfide bond was designed to respond to intracellular glutathione (GSH), enabling controlled drug release. Results: The SA-SS-CPT nanowires significantly improved CPT solubility and enabled targeted delivery to TAMs. Following GSH-responsive cleavage and CPT release, the nanowires induced DNA damage in TAMs, activating the cGAS-STING signaling pathway. This promoted TAM polarization toward the M1 phenotype, enhanced pro-inflammatory and anti-tumor immune responses, and inhibited tumor immune escape. Furthermore, SA-SS-CPT synergistically improved the efficacy of PD-L1 blockade immunotherapy, remodeling the tumor immune microenvironment. Conclusions: The SA-SS-CPT nanoplatform effectively targets TAMs, repolarizes them to an anti-tumor M1 phenotype, and activates the cGAS-STING pathway. It shows strong potential for overcoming tumor immune escape and synergizing with PD-L1 checkpoint blockade to achieve significant tumor clearance. Full article

Aristolochic acid (AA), a naturally occurring compound found in Aristolochia plants, is a well-established nephrotoxin and Group 1 carcinogen. Emerging evidence suggests a potential link between AA exposure and hepatocellular carcinoma (HCC), one of the leading causes of cancer-related mortality worldwide. This review critically evaluates current knowledge on AA’s hepatic metabolism, its formation of persistent DNA adducts, and the induction of inflammatory responses in the liver. Based on preclinical and indirect human evidence, we propose a working hypothesis that AA may contribute to hepatocarcinogenesis through a dual mechanism: genotoxic (primarily via H-ras and p53 mutations resulting from AA-DNA adducts) and non-genotoxic (via chronic inflammation involving IL-6, TNF-α, and NF-κB activation, as well as epithelial–mesenchymal transition). We note, however, that these mechanisms remain to be validated in human cohorts and do not yet establish causality. Recent studies have identified novel mechanisms, including PDK4-mediated mitochondrial dysfunction, ferroptosis inhibition via p53 hijacking, and ARID1A deficiency as a susceptibility factor. A recent meta-analysis quantified a significantly increased risk of liver cancer following AA exposure in epidemiological studies. While direct causal evidence in humans remains limited, the high mutational burden observed in AA-exposed liver tissues warrants caution. Nevertheless, the primary public health priority pertains to the prevention of AA exposure. Further epidemiological and mechanistic studies are urgently needed. Full article

Mastitis limits yak dairy production and is associated with lipopolysaccharide (LPS)-mediated inflammation in yak mammary epithelial cells (YMECs). This study aimed to investigate the protective effect of caffeic acid (CA) against LPS-induced cellular injury and to elucidate the underlying mechanisms, with a particular focus on autophagy regulation via the NF-κB signaling pathway. LPS exposure strikingly reduced cellular viability and increased intracellular reactive oxygen species (ROS) levels, accompanied by activation of the NF-κB pathway. Furthermore, it increased the expression of pro-inflammatory cytokines (TNF-α, IL-8, and IL-1β). In addition, LPS enhanced endoplasmic reticulum (ER) stress and Ca²⁺ dysregulation, increased LC3-II/LC3-I ratio, and reduced synthesis of α-casein and β-casein. Pretreatment with CA resulted in the effective alleviation of these alterations by restoring cellular viability, suppressing inflammatory responses, and normalizing autophagy-related markers. Additionally, inhibition of Nrf2 reversed the partial reversal of the protective effects of CA, resulting in increased ROS accumulation and autophagy activation, but did not impact NF-κB suppression. These findings indicate that CA attenuates LPS-induced inflammatory injury in YMECs involved in both Nrf2-dependent and independent pathways. These findings provide a mechanistic analysis of yak mastitis pathogenesis and CA potential as a natural therapeutic for improving mammary health and milk quality in yak dairy systems. Full article

Hypertension is a common cardiovascular disorder, and current pharmacological treatments are often associated with significant side effects, highlighting the need for safer alternatives. Probiotics and their postbiotics have emerged as promising candidates due to their favorable safety profiles. This study evaluated the potential of Lactobacillus plantarum IOB602 and its 602P postbiotic to attenuate hypertension-induced damage. We first assessed their ACE inhibitory activity in vitro. Subsequently, we investigated their protective effects against organ damage and the underlying mechanisms in L-NAME-induced hypertensive rats using biochemical assays, real-time qPCR, histopathological analysis, and 16S rRNA sequencing. In vitro results showed that IOB602 exhibited strong tolerance to simulated gastric acid and bile salts, indicating good gastrointestinal survivability. Both the culture supernatant and the postbiotic displayed significant ACE inhibitory activity, with the postbiotic achieving an inhibition rate of 82.21%. In vivo, treatment with IOB602 or 602P significantly reduced plasma angiotensin II levels, upregulated the PI3K-Akt-eNOS pathway, restored nitric oxide bioavailability, and attenuated oxidative stress and inflammatory responses in hypertensive rats. Histological analysis revealed that both interventions alleviated pathological damage in the thoracic aorta, heart, and kidneys. Furthermore, IOB602 and its postbiotic reshaped the gut microbiota composition by decreasing harmful genera such as Ruminococcus and enriching beneficial taxa including Akkermansia and Christensenellaceae. In conclusion, L. plantarum IOB602 and its 602P postbiotic show potential for development as functional foods or pharmaceutical adjuvants for the treatment of hypertension-induced organ damage.: Full article

Cannabis sativa L. is a medicinal plant cultivated globally due to its remarkable historical and scientific relevance. Through the consumption of its flowers, also referred to as inflorescences, which contain a high content of cannabinoids, terpenes and polyphenols, the therapeutic properties of C. sativa can be harnessed. This study therefore aimed to determine the chemical profile, antioxidant and anti-inflammatory activities of the essential oils (EOs) obtained from the fresh and dried flowers of two C. sativa cultivars, Lifter and Cherrywine, grown in Komga, South Africa, to assess which cultivar has greater biological potential. The chemical profiles of the hydro-distilled EOs were analyzed by gas chromatography–mass spectrometry (GC-MS), while the in vitro antioxidant and anti-inflammatory activity of the EOs was analyzed using the DPPH and EAD methods, respectively. The identified constituents from the EOs were molecularly docked against NOX2 and NIK (NF-κB-inducing kinase) protein, which are implicated in oxidative stress. The afforded EOs were yellow (pale and bright yellow) in color with a sweet to mildly sweet aroma description. A total of 51 constituents were identified in both fresh and dry oils from the Lifter cultivar, while the Cherrywine cultivar contained a total of 44 constituents. Eighteen compounds, were found to be the main chemical constituents consistent in the flower EOs of both cultivars, notably, caryophyllene (10.71–19.96%), levo-β-pinene (1.37–13.21%), humulene (5.88–9.77%), caryophyllene oxide (4.32–7.49%), D-limonene (1.40–5.48%), α-pinene (2.22–5.22%), nerolidol (0.63–4.97%), cis-β-ocimene (0.22–4.37%), linalool (1.12–4.28%), selina-3,7(11)-diene (0.15–4.23%), humulene-1,2-epoxide (1.23–3.32%), guaiol (0.17–2.60%), (+)-β-selinene (1.20–2.51%), trans-α-bergamotene (0.68–2.37%), β-ocimene (0.90–2.27%), fenchol exo- (0.15–1.27), terpineol (0.14–1.38%) and α-terpineol (0.19–0.75%). The fresh Lifter flower oil (LFO) showed 50% inhibition at 100 μg/mL, with an IC₅₀ of 69.50 ± 4.05 µg/mL against DPPH, suggesting moderate to low radical scavenging activity. The maximum percentage inhibition response of DLFO, CFO and DCFO remained below 50% at all concentrations. The antioxidant activity of fresh LFO may be attributed to its overall chemical composition. The flower oils showed in vitro inhibition of protein denaturation; however, the high standard deviation relative to the mean IC₅₀ values limited the ability to rank the samples’ potencies. Further in silico studies on the putative constituents in the Lifter and Cherrywine cultivars revealed β-bisabolene and α-curcumene as potential molecular targets, with binding energy scores of −7.7 and −7.9 kcal/mol, respectively. Thus, the study findings highlight the promising biological importance of C. sativa inflorescences in the management of oxidative stress-related conditions. Further studies may investigate the influence of environmental growing conditions on their chemical composition, total ROS analysis, pharmacokinetic properties, and in vivo efficacy against oxidative damage to DNA, proteins and lipids. Evaluating the toxicity of the flower EOs is also recommended. Full article

Rice (Oryza sativa L.) is a staple food crop, feeding more than 3.5 billion people. With the increasing demand for food in the 21st century, weed infestation poses the most significant biotic threat to global food security, and herbicides remain the most effective and economic way to manage it in field. However, weeds can rapidly adapt under herbicide selection pressure due to their high competitiveness, rapid growth, and reproductive capacity. Hence, we collected Echinochloa crus-galli populations from Heilongjiang and Hebei provinces in China and investigated their resistance mechanisms to pyrazosulfuron-ethyl (PSE), a sulfonylurea herbicide that inhibits acetolactate synthase (ALS). Dose–response experiments confirm that the resistant (R) population exhibits 52.9-fold resistance to PSE compared with the susceptible (S) population. Inhibitor bioassays with malathion and NBD-Cl, together with ALS activity assays, ALS gene sequencing, and molecular docking, collectively suggest that resistance is strongly associated with the ALS Trp-574-Leu target-site substitution, with a possible additional contribution from enhanced herbicide metabolism. However, because the S and R populations originate from geographically distinct locations, some of the observed physiological and molecular differences may also reflect inherent population variation. Specifically, the ALS W574L substitution is predicted to reduce key interactions between ALS and PSE. This study provides valuable evidence for the risk of PSE resistance evolution in E. crus-galli and elucidates the molecular mechanism conferring resistance to ALS inhibitors. Full article