Resistance Response Research Articles

Production losses caused by red leather leaf in hay and milling oats

Context Red leather leaf (RLL), caused by Neospermospora avenae, is a common foliar disease of oats in south-eastern Australia but its impact on hay and grain yield and quality is unknown. Aim We aimed to determine the effect of RLL on grain yield and quality of commercial milling oat varieties, and biomass and nutrition of hay oat varieties, with a range of host plant resistance responses by comparing fungicide and disease treatments. Methods A total of eight field experiments were conducted in 2019 and 2020; four experiments each investigated the effects of RLL on hay or milling oats. In each experiment, six or seven oat varieties were sown with a disease or fungicide imposed. RLL severity was estimated visually for each experiment. Biomass yield and quality traits at early milk development stage were measured for hay oat experiments; and grain yield and quality for the milling oat experiments. Key results RLL severity (% leaf area affected: 0–44% in hay oats and 2–61% in milling oats) varied with the season, varietal resistance, and treatments. RLL caused significant losses in most experiments, with reductions in biomass of up to 3.5 t/ha (22%) in hay oats and grain yield of up to 1.1 t/ha (21%) in milling oats. Conclusions RLL can be a severe foliar disease of oats in south-eastern Australia and cause significant losses in both hay and milling oat crops. Implications Growing varieties with resistance can effectively reduce potential loss due to RLL and growers are required to adapt fungicide strategies reflecting seasonal conditions and product type (grain or hay).

Impact of the Stress Response on Quaternary Ammonium Compound Disinfectant Susceptibility in Serratia Species

The well-known problem of antibiotic resistance foreshadows a similar threat posed by microbial resistance to biocides such as disinfectants and antiseptics. These products are vital for infection control, yet their overuse during the COVID-19 pandemic has accelerated the development of resistant microorganisms. This study investigates the molecular mechanisms underlying disinfectant resistance in Serratia sp. HRI. The transcriptomic responses of Serratia sp. HRI were used to identify significant gene expression changes during exposure to QACs and revealed increased methionine transport and polyamine synthesis. Polyamines, crucial in cellular stress responses, were notably upregulated, suggesting a pivotal role of the stress response in disinfectant resistance. Further, our susceptibility tests revealed a marked decrease in susceptibility to QACs under various stress conditions, supporting the hypothesis that stress responses, mediated by polyamines, decrease susceptibility to QACs. This research highlights polyamines as key players in disinfectant resistance, offering novel insights into resistance mechanisms and antimicrobial susceptibility. Our findings emphasise the need for continued investigation into disinfectant resistance and the role of stress responses, particularly polyamine-mediated mechanisms, to direct strategies for preserving disinfectant efficacy and developing future antimicrobial agents.

A Detailed Proteomics and Metabolomics Landscape Sheds Light on the Mechanistic Insights Into the Resistance Response of Transgenic Pigeon Pea Against Wilt Stress.

Pigeon pea, vital for farmers in semi-arid regions, suffers yield losses from Fusarium wilt caused by Fusarium udum. This study demonstrates that introducing the rice oxalate oxidase 4 (Osoxo4) gene significantly boosts wilt resistance. Enhanced resistance in transgenic lines was confirmed through gene expression analysis, enzyme activity assays, biochemical assessments, histochemical staining and in vitro and in vivo bioassays, including spore germination tests. We performed proteomics and metabolomics analyses to investigate mechanisms of enhanced resistance. LC-MS/MS-based label-free proteomics of wilt-infected transgenic and wild-type pigeon pea leaves identified 2386 proteins, with 1048 showing significant abundance changes-738 upregulated and 310 downregulated-in transgenic plants. Notably, proteins such as HMG1/2-like protein, Putative nucleosome assembly protein C364.06, DEAD-box ATP-dependent RNA helicase 3, Lipoxygenase 1, Annexin D1 and Annexin-like protein RJ4 were significantly upregulated, indicating their potential role in developing wilt-resistant cultivars. Metabolomic analysis showed elevated levels of amino acids, sugars, oxalic acid, sugar alcohols and myo-inositol in transgenic pigeon pea, with upregulated pathways in Sugar and Starch Metabolism and Inositol Phosphate Metabolism, indicating enhanced resilience to wilt stress. This study highlights unique regulatory proteins and metabolites, offering insights into stress adaptation and guiding genetic interventions for breeding disease-resistant pigeon pea varieties.

Experimental Investigation of Towing of a Semi-submersible Floating Offshore Wind Turbine

Abstract The offshore floating wind energy sector is poised for exponential growth in the coming decades. A pivotal challenge within this context is the imperative to substantially decrease the levelized cost of energy (LCOE) to enhance competitiveness. A significant proportion of these LCOE costs are attributable to the towing operations entailed in both the installation of assembled floating wind turbines and the maintenance of major components. Semi-submersibles, characterized by multiple columns and pontoons, represent the prevailing conceptual approach in the industry due to their versatility across varying water depths and their cost-effectiveness in terms of mooring and transportation. Towing model tests for the semi-submersible INO WINDMOOR floating wind turbine have been conducted in the Ocean Basin at SINTEF Ocean. The primary objective of these tests is to investigate critical aspects such as towing resistance and dynamic responses, including vortex-induced motion (VIM) and galloping. This paper presents the experimental set-up and initial findings from the model tests. Through comparative data analysis of selected cases, an enhanced and insightful understanding of the intricate fuid-structure interactions is expected to be achieved. Additionally, it highlights the identification of knowledge gaps and research imperatives aimed at expanding the towing operational criteria, with the ultimate goal of reduction of installation and maintenance costs.

Characterisation of the Phenotypic Reaction of Brazilian Soybean Genotypes to Sclerotinia sclerotiorum Under Controlled Conditions

ABSTRACTWhite mould is a disease caused by the fungus Sclerotinia sclerotiorum, and it is considered one of the most devastating diseases in soybean crops, causing huge losses in productivity. In this study, we aimed to contribute to the genetic control of this disease by characterising the phenotypic reaction of 67 Brazilian soybean genotypes to S. sclerotiorum under controlled conditions. Plants were artificially inoculated with mycelium discs when they reached the four‐node phenological stage. Symptoms of white mould developed in all soybean genotypes. The resistance reaction was characterised by measuring the length of lesions on the main stem at 7 days after inoculation. Of the 67 genotypes evaluated, nine showed greater resistance to S. sclerotiorum, including 17S‐01443‐L8, 16S‐00630‐L4, GER_00003, 13S‐00001‐L2/FPS 2457 RR, BMX Torque I2X, P95Y02 IPRO, 17S‐00842‐L5, HO Pirapó IPRO and TMG 2359 IPRO. Twenty‐three genotypes showed an intermediate response, while 35 genotypes showed greater susceptibility to S. sclerotiorum. Further studies should be conducted under field conditions with the soybean genotypes that showed greater resistance response to S. sclerotiorum under controlled conditions.

Transcriptome and Physiological Analyses of Resistant and Susceptible Pepper (Capsicum annuum) to Verticillium dahliae Inoculum

Pepper (Capsicum annuum) is a globally important vegetable, and Verticillium wilt is an important disease affecting peppers and is caused by Verticillium dahliae, which can severely reduce yields. However, the molecular mechanisms underlying the responses of pepper to infection by V. dahliae are largely unknown. We performed physiological and transcriptome analysis using resistant and susceptible pepper cultivars inoculated with V. dahliae. Compared to the susceptible cultivar MS66, the resistant cultivar MS72 retained higher chlorophyll content and lower malondialdehyde content after inoculation. At 3 days after inoculation (DAI), compared with MS66, 534 differentially expressed genes (DEGs) were identified in MS72. At 5 DAI, 2392 DEGs were identified in MS72 compared with MS66. The DEGs in MS72 were mainly enriched in the cell wall and photosynthesis-related Gene Ontology terms, as well as in pathways such as cutin, suberin, wax biosynthesis, phenylpropanoid biosynthesis, and photosynthesis. Using weighted gene co-expression network analysis, 36 hub genes involved in the resistance response were identified, including the transcription factor bHLH93 (Capana04g000815), defense-like protein 1 (MSTRG.5904), and miraculin-like (Capana10g002167). Our findings contribute to a more comprehensive understanding of the response mechanism of pepper to V. dahliae inoculation, providing new avenues for improving pepper resistance through breeding programs.

Methyl jasmonate mitigates Fusarium graminearum infection in wheat by inhibiting deoxynivalenol synthesis.

Methyl jasmonate (MeJA), a plant growth regulator, coordinates a diverse array of physiological responses, including the inhibition of seed germination, modulation of secondary metabolite biosynthesis, and activation of defence responses. The external application of MeJA has been demonstrated to effectively diminish the severity of fungal diseases. Here, we unveil a novel mechanism through which exogenous MeJA alleviates Fusarium head blight (FHB) by inhibiting the synthesis of deoxynivalenol (DON) in Fusarium graminearum, rather than by enhancing the wheat resistance response. MeJA treatment reduced the infection by wild-type F. graminearum in wheat coleoptiles, but exhibited no significant influence on that of the DON-deficient mutant strain (∆Tri5). The production of DON in F. graminearum was significantly inhibited both in vitro and in planta. MeJA affected the expression of genes related to DON biosynthesis, without influencing the formation of toxisomes as observed under microscopic analysis. Exogenous MeJA demonstrated a limited impact on the early genes of plant jasmonic acid signalling pathway, in contrast to the wild-type pathogen strain, which induced the upregulation of these genes. The expression levels of defence marker genes induced by MeJA were notably lower compared to those induced by the pathogen. This study elucidates the molecular mechanisms of MeJA in modulating the wheat-F. graminearum interaction, providing new insights into the development of environmentally friendly strategies against fungi.

Shifts in plant architecture drive species-specific responses to drought in a Sorghum recombinant inbred line population.

Drought stress severely impedes plant growth, development, and yield. Therefore, it is critical to uncover the genetic mechanisms underlying drought resistance to ensure future food security. To identify the genetic controls of these responses in Sorghum, an agriculturally and economically important grain crop, an interspecific recombinant inbred line (RIL) population was established by crossing a domesticated inbred line of Sorghum bicolor (TX7000) with its wild relative, Sorghum propinquum. This RIL population was evaluated under drought conditions, allowing for theidentification of quantitative trait loci (QTL) that contribute to drought resistance. We detected eight QTL in the drought population that explain a significant portion of the observed variation for four traits (height, aboveground biomass, relative water content, and leaf temperature/transpiration). The allelic effects of, and the candidate genes within, these QTL emphasize: (1) the influence of domestication on drought-responsive phenotypes, such as height and aboveground biomass, and (2) how control of water uptake and/or loss can be driven by species-specific plant architecture. Our findings shed light on the interconnected roles of shoot and root responses in drought resistance as it relates to regulation of water uptake and/or loss, while the detected allelic effects demonstrate how maintenance of grain production and yield under drought is a likely result of domestication-derived drought tolerance.

Ultrasonic Production of Chitosan Nanoparticles and Their Application Against Colletotrichum gloeosporioides Present in the Ataulfo Mango

In Mexico, the Ataulfo mango crop faces significant challenges due to anthracnose, a disease caused by the fungus Colletotrichum gloeosporioides. The need to use eco-friendly fungicides is crucial to avoid the use of harmful synthetic chemicals. This study aimed to prepare chitosan nanoparticles through a simple and effective ultrasound-assisted top-down method, with high antifungal efficiency. The nanoparticles were prepared from chitosan (DD = 85%, MW = 553 kDa) and Tween 20 under constant sonication. The formation of the nanoparticles was initially confirmed by Fourier-transform infrared (FTIR) spectroscopy; and their physicochemical properties were subsequently characterized using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The antifungal potential of the chitosan nanoparticles against the phytopathogen Colletotrichum gloeosporioides was evaluated with isolated fungi obtained directly from mango tissues showing anthracnose symptoms in the state of Guerrero, Mexico. The fungus was identified through SEM imaging, showing a regular and smooth conidial layer, with cylindrical shape (r = 2 µm, h = 10 µm). In vitro tests were conducted with three different concentrations of chitosan nanoparticles to assess their inhibitory effects. After seven days of incubation, a maximum inhibition rate of 97% was observed with the 0.5% nanoparticle solution, corresponding to a fungal growth rate of 0.008 cm/h. At this time, the control mycelial growth was 7 cm, while the treated sample reached a radius of 0.55 mm. These results demonstrated the antifungal effect of the nanoparticles on the membrane and cell wall of the fungus, suggesting that their composition could induce a resistance response. The inhibitory effect was also influenced by the particle size (30 nm), as the small size facilitated penetration into fungal cells. Consequently, the parent compound could be formulated and applied as a natural antifungal agent in nanoparticle form to enhance its activity. The method described in this study offers a viable alternative for the preparation of chitosan nanoparticles, by avoiding the use of toxic reagents.

Drug repurposing: An antidiabetic drug Ipragliflozin as Mycobacterium tuberculosis sirtuin-like protein inhibitor that synergizes with anti-tuberculosis drug isoniazid

The surge of drug-resistant Mycobacterium tuberculosis (DR-TB) impedes the World Health Organization's efforts in ending TB and calls for new therapeutic formulations. M. tuberculosis sirtuin-like protein Rv1151c is a bifunctional enzyme with both deacetylation and desuccinylation activities, which plays an important role in M. tuberculosis drug resistance and stress responses. Thus, it appears to be a promising target for the development of new TB therapeutics. In this study, we screened 31,057 ligand compounds from seven compound libraries in silico to identify inhibitors of Rv1151c. Ipragliflozin can bind to Rv1151c and interact stably. Ipragliflozin can change the acylation level of M. tuberculosis by inhibiting Rv1151c and effectively inhibit the growth of M. tuberculosis H37Rv and M. smegmatis. It can potentiate the first-front anti-TB drug isoniazid. As an antidiabetic drug, Ipragliflozin can be potentially included in the regimen to treat diabetes-tuberculosis comorbidity.

The influence of plant genomics on plant evolution

With the increasing demand for high-quality tea, the genetic basis of ideal traits of tea plants has been widely concerned. The research on tea tree genomics, specifically focusing on “Longjing 43”, provides significant insights into plant evolution and breeding. “Longjing 43” was chosen due to its complex genome and economic importance. The study successfully assembled its genome to the chromosome level, revealing a large and heterogeneous genome with numerous repetitive sequences. Comparative genomics showed that hybridization has been a key driver of genetic diversity and adaptability in tea plants. These findings are crucial for developing marker-assisted selection (MAS) techniques, improving traits such as disease resistance, flavor, and stress response. Moreover, the research underscores the role of tea tree genomics in preserving cultural heritage and promoting economic benefits through enhanced tea quality. This study contributes to the broader understanding of plant genomics by illustrating the evolutionary processes and potential applications in agriculture, conservation, and industry, thus offering a comprehensive tool for future plant breeding and genetic improvement strategies.

Multi-component resistance responses of melon to zucchini yellow mosaic virus.

A major resistance gene of the melon accession PI414723 to zucchini yellow mosaic virus (ZYMV) is located at the Zym-1 locus on chromosome 2, but the underlying defense mechanisms are poorly understood. The physiological responses and expression of selected genes at Zym-1 were assessed in PI414723 and in the susceptible genotype Védrantais. Viral titers and the expression of genes related to systemic acquired resistance (SAR) were evaluated in inoculated (Inoc) and non-inoculated (Non-Inoc) portions of the cotyledons at 3, 7 and 10 days after inoculation (dai) and in apical leaves at 10 dai. ZYMV was detected in both portions of the cotyledons but not in the apical leaves of PI414723 plants. Also, ZYMV was recovered in a susceptible zucchini only from Inoc portions at 3 dai. By contrast, in Védrantais ZYMV was detected and recovered from all tissues at high concentrations. Starchy local lesions and accumulation of transcripts of the SAR marker genes PR1 and PR4 were also detected in the resistant genotype. Plus, transcripts of one candidate resistance gene analog previously located at Zym-1 and of two melon homologs of restricted tobacco etch virus movement 2 (RTM2) genes located close to Zym-1, accumulated only in PI414723. It is proposed that resistance results from the combined action of the R gene, involved in restricting ZYMV replication after a supposed recognition event and of the RTM genes which impact viral systemic movement to distal apical tissues.

Acute vasoreactivity testing for severe pulmonary hypertension associated with lung disease

Abstract Background Pulmonary hypertension results in clinical deterioration and increases mortality risk in patients with lung disease (LD), including chronic obstructive pulmonary disease, interstitial lung disease and combined pulmonary fibrosis and emphysema. Though acute vasoreactivity testing predicts long term-survival of patients with pulmonary arterial hypertension (PAH), its clinical impact for patients with pulmonary hypertension associated with LD (LD-PH) remains unknown. Purpose The purpose of this study is to clarify the clinical impact of acute vasoreactivity testing using inhaled nitric oxide for severe LD-PH. Methods We retrospectively reviewed 65 consecutive patients with LD-PH between January 2014 and December 2022; 48 patients (73 [68–78] years; males, 81%; median follow-up period 23 [7–35] months) with severe pulmonary hypertension who underwent acute vasoreactivity testing were included. We divided the patients based on a median pulmonary vascular resistance (PVR) response (−15%) in acute vasoreactivity testing into the high-responder (PVR response ≦−15%) and the low-responder (PVR response >−15%) groups. Results Acute vasoreactivity testing significantly decreased mean pulmonary arterial pressure (mPAP) (from 41 [34–48] to 36 [31–40] mmHg, P<0.01) and PVR (from 10.7 [8.3–13.8] to 8.9 [6.6–11.4] Wood units, P<0.01). The high-responder group had better long-term survival than the low-responder group (P = 0.03). Univariate Cox regression analysis showed that the prognostic factors for better survival included younger age, high-responder to acute vasoreactivity testing, and PAH-specific therapy (P <0.01, 0.04, 0.03, respectively). There were correlations between the PVR response at acute vasoreactivity testing and improvement in mPAP (R=0.40, P=0.03) or PVR (R = 0.47, P <0.01) with PAH-specific therapy. Conclusions PVR response at acute vasoreactivity testing was associated with better long-term survival and haemodynamic improvement with PAH-specific therapy. Acute vasoreactivity testing may be useful to predict the responders to PAH-specific therapy and long-term survival in patients with severe LD-PH.

The interplay between coronary microvascular resistance, arterial reservoir function and coronary flow reserve: unravelling the significance of high microvascular resistance

Abstract Background Beyond the observation that patients with low CFR indicating presence of coronary microvascular dysfunction (CMD) have an unfavourable prognosis compared to patients with preserved CFR, recent large multicentre trials [1-2] have shown that increased minimal hyperaemic microvascular resistance (HMR or IMR) ,neither on top of the low CFR nor alone, does not play a role as a prognostic factor for ischemia in nonobstructive coronary artery disease (INOCA) patients. Purpose This study investigates the pathophysiological interactive processes in CMD and no-CMD groups with high and low HMR taking into account potential adaptive mechanisms that alter arterial reservoir function [3] associated with microvascular resistance and systemic vasomotor response in INOCA patients. Methods Analysis was conducted on 312 unique unobstructed vessels (FFR>0.80) from 258 patients (73% male) enrolled in the DEFINE-FLOW [4] study. CFR and HMR were quantified using intracoronary Doppler and pressure measurements. Vessels were categorized into four groups based on high and low CFR and HMR using the best available cut-off values (2.5 for both). Arterial reservoir capacity (ARC) and related parameters [3] were quantified using reservoir-excess pressure (Preservoir and Pexcess) analysis of averaged aortic and distal coronary pressure waveforms in CMD (CFR<2.5) and no-CMD (CFR≥2.5) subgroups. (Figure 1-2) Results Compared to vessels without CMD, functional and structural CMD have increased Pexcess (p:0.007) and a rapid decline in diastolic pressure (DRCcoronary p<0.001, DRCaortic, p<0.05), indicating the ongoing systemic hemodynamic superfluous state despite locally suppressed resting blood flow in the structural CMD. Higher baseline microvascular resistance (BMR) was associated with increased reservoir pressure (r:0.302, p<0.001). The vessels with preserved CFR despite high HMR are characterised by uniquely increased ARC (p:0.014), effectively diminished Pexcess (p:0.010), which parallels the local (highest BMR p<0.001) and global (lowest DRCaortic, p<0.05) vasomotor response, that normalizes the systemic and local hyperperfusion, and ultimately regains an adequate flow reserve (CFR) (p<0.001). The high HMR in this group was mainly due to increased resting tonus unlike structural CMD, evident by the highest RRR (BMR/HMR).(p<0.001) (Figure 1-2) Conclusion(s) The high HMR despite preserved CFR vessels form a unique-adaptive group, characterised by substantially increased arterial reservoir capacity and effectively diminished Pexcess, by means of an adaptive vasomotor response which manifests locally in the coronary bed as pronouncedly augmented BMR & RRR, and globally as reduced DRC in the aortic pressure waveform. This adaptive myogenic response normalising resting flow and ongoing systemic and local hyperperfusion ultimately regains an adequate flow reserve (CFR).Figure 1.Methods and Main FindingsFigure 2.Visual Abstract

Recent advances in mRNA-based cancer vaccines encoding immunostimulants and their delivery strategies

The high prevalence of drug resistance, relapse, and unfavorable response rate of conventional cancer therapies necessitate the development of more efficient treatment modalities. Immunotherapy represents a novel therapeutic approach to cancer treatment in which the immune system's potential is harnessed to recognize and eliminate tumor cells. mRNA cancer vaccines, as a burgeoning field of immunotherapy, have recently drawn particular attention, and among mRNAs encoding tumor-associated antigens, tumor-specific antigens, and immune stimulatory factors, the latter has been relatively less explored. These immunostimulatory mRNAs encode a range of proteins, including stimulatory ligands, receptors, enzymes, pro-inflammatory cytokines, and inhibitory binding proteins, which collectively augment the host immune system's ability against cancerous cells. In this review, we aimed to provide a comprehensive account of mRNA-based cancer vaccines encoding immune stimulants, encompassing their current status, mechanisms of action, delivery strategies employed, as well as recent advances in preclinical and clinical studies. The potential challenges, strategies and future perspectives have also been discussed.

Development of infectious clones of mungbean yellow mosaic India virus (MYMIV, Begomovirus vignaradiataindiaense) infecting mungbean [Vigna radiata (L.) R. Wilczek] and evaluation of a RIL population for MYMIV resistance.

Yellow mosaic disease (YMD) is a major constraint for the low productivity of mungbean, mainly in South Asia. Addressing this issue requires a comprehensive approach, integrating field and challenge inoculation evaluations to identify effective solutions. In this study, an infectious clone of Begomovirus vignaradiataindiaense (MYMIV) was developed to obtain a pure culture of the virus and to confirm resistance in mungbean plants exhibiting resistance under natural field conditions. The infectivity and efficiency of three Agrobacterium tumefaciens strains (EHA105, LBA4404, and GV3101) were evaluated using the susceptible mungbean genotype PS16. Additionally, a recombinant inbred line (RIL) population comprising 175 lines derived from Pusa Baisakhi (MYMIV susceptible) and PMR-1 (MYMIV resistant) cross was developed and assessed for YMD response. Among the tested Agrobacterium tumefaciens strains, EHA105 exhibited the highest infectivity (84.7%), followed by LBA4404 (54.7%) and GV3101 (9.80%). Field resistance was evaluated using the coefficient of infection (CI) and area under disease progress curve (AUDPC), identifying seven RILs with consistent resistant reactions (CI≤9) and low AUDPC (≤190). Upon challenge inoculation, six RILs exhibited resistance, while RIL92 displayed a resistance response, with infection occurring in less than 10% of plants after 24 to 29 days post inoculation (dpi). Despite some plants remaining asymptomatic, MYMIV presence was confirmed through specific PCR amplification of the MYMIV coat protein (AV1) gene. Quantitative PCR revealed a very low relative viral load (0.1-5.1% relative fold change) in asymptomatic RILs and the MYMIV resistant parent (PMR1) compared to the susceptible parent (Pusa Baisakhi). These findings highlight the potential utility of the developed infectious clone and the identified MYMIV-resistant RILs in future mungbean breeding programs aimed at cultivating MYMIV-resistant varieties.

A Highly Sensitive, Conductive, and Flexible Hydrogel Sponge as a Discriminable Multimodal Sensor for Deep‐Learning‐Assisted Gesture Language Recognition

AbstractFlexible multimodal sensors have gained increasing popularity for applications in healthcare and extreme environment operations owing to their all‐around environmental perception and data acquisition capabilities. However, fabricating a magnetism‐mechanics‐humidity multimodal sensor that possesses high sensitivity without signal overlapping while in a facile methodology remains a great challenge. Herein, a highly sensitive, conductive, and flexible hydrogel sponge sensor with discriminable magnetism, mechanics, and humidity sensing capability is proposed, which shows stable pore size (19.30 µm) and satisfactory mechanical properties based on the synergistic hydrogen bonding among sodium alginate, poly(vinyl alcohol) and glycerol. The proposed sensors can not only display favorable humidity sensing ability with rapid response/recovery time (2.5/4 s) but also possess enhanced sensitivities (a gauge factor of 0.46 T−1 for magnetic field, −1.16 kPa−1 for pressure), superior stability and durability (over 8000 cycles). Benefiting from the separated capacitive and resistive response signals, the sensors can precisely distinguish the magnetic, mechanical, and humidity stimuli without cross‐talk. Further, the sensor arrays assisted by the deep learning algorithm are developed to realize gesture language recognition with a high accuracy of 99.17%. It can be believed that this high‐performance sensor will have good prospects in future soft electronics and human‐machine interaction systems.

Fabrication of pyridine incorporated and O-doped g-C3N4/COF: A type-II heterojunction for enhanced hydrogen production under visible light irradiation

The fabrication of heterojunction photocatalysts is important for achieving highly efficient electron transfer, charge separation, and catalytic activity. In this study, we report the successful creation of a type II heterojunction between pyridine incorporated and O-doped g-C3N4 (POCN) and a covalent organic framework (COF). The heterojunction formation significantly reduced the fluorescence intensity of the POCN/COF, indicating effective separation of electron-hole pairs. Additionally, POCN/COF demonstrated excellent interface charge transfer resistance and photocurrent response. Its hydrogen production rate was remarkably high at 3500 μmol g⁻1 h⁻1, about 1.6 times that of pure COF (2200 μmol g⁻1 h⁻1) and 3.5 times that of the physical mixture (1000 μmol g⁻1 h⁻1), and it also exhibited enhanced stability. This indicates that it can be effectively fabricated into a heterojunction of POCN and COF. The optimal value for adding POCN was approximately 5 wt% of COF. This demonstrates greater activity compared to other composite catalysts made from graphitic carbon nitride and COF. This study presents a valuable approach for fabricating reusable heterojunction photocatalytic systems and efficiently generating hydrogen from natural energy sources.

JAK Inhibitors for Myelofibrosis: Strengths and Limitations.

The landscape of myelofibrosis (MF) has changed since the discovery of the JAK2 V617F mutation and subsequent development of JAK inhibitors (JAKis). However, treatment with JAKis remain a challenge. In this review we critically analyze the strengths and limitations of currently available JAK inhibitors. In MF patients, JAK inhibitors have been associated with reduced symptom burden and spleen size, as well as improved survival. However, durability of response and development of treatment resistance remain an issue. Recently, there has been increased efforts to optimize treatment with the development of highly selective JAK inhibitors, as well as use of combination agents to counter disease resistance through targeting aberrant signaling pathways. Treatment of MF patients with JAKi therapy can be challenging but the development of more potent and selective JAK inhibitors, as well as combination therapies, represent exciting treatment advances in this field.

Atypical Exon 2/3 Mutants G48C, Q43K, and E37K Present Oncogenic Phenotypes Distinct from Characterized NRAS Variants.

NRAS belongs to the RAS family of GTPases. In colorectal cancer (CRC), NRAS mutations are rare compared to KRAS, but may lead to worse outcomes. We report the functional characterization of the novel NRAS mutants-G48C, Q43K, and E37K-identified in Filipino young-onset CRC patients. Unlike previously characterized NRAS mutants with no apparent effects on cell proliferation, these mutants enhanced proliferation of both HCT116 and NIH3T3 cells. This was confirmed in 3D spheroid assays to mimic the spatial organization of cells. G48C and E37K showed apoptosis resistance in both cell lines, and Q43K showed resistance in HCT116 cells. All three showed no effect on cellular migration in NIH3T3, but G48C enhanced the migration rate of HCT116 cells. Actin staining of NIH3T3 cells expressing the mutants showed a shrunken cytoplasm and transient structures associated with motility and invasiveness. Docking simulations show that GDP is only able to bind fully within the binding pocket of wild-type NRAS, but not in the mutants. Further, G48C, Q43K, and E37K all have less negative ΔG values, indicating a weaker GDP-binding affinity compared to wild-type NRAS. Taken together, the results suggest that oncogenic readouts of NRAS mutants are codon- and mutation-specific, with potential repercussions on the aggressiveness, resistance, and therapeutic response.