Emotional interference and attentional bias in compulsive sexual behaviors disorder - An fMRI study on heterosexual males.

Background and aims: Despite the inclusion of the Compulsive Sexual Behavior Disorder (CSBD) in the 11th edition of the International Classification of Diseases, emotional and cognitive impairments related to CSBD remains unclear. This study aimed to investigate the behavioral and neuronal effects of emotional interference on cognition among CSBD patients. Methods: Thirty heterosexual males with CSBD and matched healthy controls (HC) were studied with the Emotional Stroop Task using 5 categories of emotionally arousing words (sex-related, positive, fear-related, negative, neutral) during functional magnetic imaging. Results: At the behavioral level, we found the main effect of the condition: sex-related words evoked a stronger Stroop effect than other conditions. At the neural level, we found a significant group effect. Among CSBD patients processing of sex-related words was related to increased activity in the right putamen, right thalamus, hippocampi, and left pulvinar, when compared to HC. We also found a negative correlation between neuronal activation and time spent on sexual activity during the week preceding study and numerous group differences in brain regions connected to the emotional and motivational processing of sexually explicit material, correlating with CSBD symptoms. Conclusions: Behavioral results indicate a specific attentional bias toward sex-related stimuli in both groups, while neural data uncovered stronger reactivity to sex-related words in CSBD compared to HC. This reactivity is related to CSBD symptoms and provides evidence for the interference of sex-related stimuli with cognition. Such results are firmly in line with the Incentive Salience Theory and conceptualizing CSBD as a behavioral addiction.

Living well with chronic pain: a 12-month randomized controlled trial revealing impact from the digital pain self-management program EPIO.

Introduction: Chronic pain affects a wide range of physical and psychological aspects of life for those impacted. Psychosocial treatment approaches may be of support, but outreach is still limited. Objectives: To evaluate the efficacy of EPIO, an evidence-informed, user-centered digital self-management intervention for people with chronic pain, in a 12-month randomized controlled trial. Methods: People living with chronic pain (N = 266) were randomized to the EPIO intervention (n = 132) or a usual-care control group (n = 134). The intervention was delivered in a simple blended care model, and outcome measures collected at baseline, 6 months, and 12 months. Generalized linear models for repeated measures were fitted to compare groups over time. Results: Participants were primarily female (81%), median age 49 years (range 22-78), with heterogeneous pain conditions, and had lived with pain >5 years (77.6%). A mixed linear model with all timepoints included revealed no statistically significant group differences for the primary outcome of pain interference. Significant psychological benefits in favor of the intervention group were however detected for depression (P = 0.022), self-regulatory fatigue (P = 0.024), vitality (P = 0.016), and mental health (P = 0.047). Baseline to 12-month changes showed additional favorable effects for anxiety (between-group mean differences [MDs] = 0.79, P = 0.047), depression (MD = 1.08, P = 0.004), self-regulatory fatigue (MD = 2.42, P = 0.021), pain catastrophizing (MD = 2.62, P = 0.009), and health-related quality of life. Conclusions: The EPIO program aims to improve outreach of evidence-based pain self-management interventions. Findings demonstrate how using EPIO can lead to sustainable psychological change, enhancing mental health and health-related quality of life for people suffering from pain, providing a chance to live well with the pain.

Diagnostic pitfalls in assessment of ferritin following CAR-T-cell therapy: Understanding the hook effect.

The hook effect is a well-described but clinically underappreciated immunoassay interference, where a falsely lowered result is caused by analyte excess. We describe a situation in which ferritin immunoassay results from a 27-year-old female with immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome were more than 1000 times lower at a reference laboratory than those determined in-house after dilution. This case underscores the importance for clinical care providers to be aware of the impact of the hook effect on ferritin measurements, and to promptly communicate with the laboratory when there are discrepancies between clinical symptoms and test results.

GNSS interference and spoofing dataset.

GNSS signals are vulnerable to spoofing and interference, which poses a threat to the security of critical national infrastructure. GNSS data sets with spoofing and jamming are lacking, which hinders the research of GNSS anti-spoofing and anti-interference techniques. This data article presents a dataset recorded by a low-cost sensor deployed on the balcony at the 5th floor of the Science Hall of Yunnan University (25°3'26'' N, 102°41'55'' E). The sensor suite includes a GNSS antenna, a u-blox GNSS receiver and an embedded computer. In the experiment, interferences including spoofing and jamming were irregularly emitted using a SDR HackRF One and a commercial jammer, respectively. The dataset collected by the receiver consists of two parts: (1) raw data; (2) processed data. The types of the raw data include hardware information, satellite information and receiver parameters of GPS, Campass, Galileo, GLONASS and QZSS systems. The processed data are extracted from the raw data, including the signals, Doppler shift, pseudorange observations, carrier phase, position (latitude, longitude, and altitude), satellite azimuth and elevation angles, etc. The provided datasets are interesting for the GNSS security, anti-jamming and anti-spoofing mechanisms based scientific communities.

Three Birds with One Stone: Copper Ions Assisted Synergistic Cuproptosis/Chemodynamic/Photothermal Therapy by a Three-Pronged Approach.

Copper is indispensable to organisms, while its homeostatic imbalance may interference normal cellular physiological processes and even induce cell death. Artificially regulating cellular copper content provides a viable strategy to activate antineoplastic effect. In light of this, a copper ions homeostasis perturbator (CuP-CL) with cinnamaldehyde (Cin) packaging and thermosensitive liposome coating is reported. Following laser exposure, the doping of Cu2+ in polydopamine initiates enhanced photothermal therapy (PTT) and unlocks the outer layer of liposome, leading to the release of copper ions and Cin in tumor microenvironment with mild acidity and high glutathione (GSH) levels. The liberative Cu2+ can evoke cuproptosis and chemodynamic therapy (CDT). Meanwhile, leveraging the merits of H2O2 supply and GSH consumption, Cin serves as a tumor microenvironment regulator to amplify Cu2+ mediated cuproptosis and CDT. Additionally, the positive feedback effects of "laser-triggered PTT, PTT accelerates reactive oxygen species (ROS) generation, ROS amplifies lipid peroxide (LPO) accumulation, LPO mediates heat shock proteins (HSPs) clearance, down-regulated HSPs promote PTT" entailed the overall benefit to therapeutic outcomes. Both in vitro and in vivo results corroborate the remarkable antineoplastic performance of CuP-CL by the synergy of cuproptosis/CDT/PTT. Collectively, based on the three-pronged approach, this work plots a viable multimodal regimen for cancer therapy.

Regional brain activity and neural network changes in cognitive-motor dual-task interference: A functional near-infrared spectroscopy study.

Previous neuroimaging studies have reported dual-task interference (DTi) and deterioration of task performance in a cognitive-motor dual task (DT) compared to that in a single task (ST). Greater frontoparietal activity is a neural signature of DTi; nonetheless, the underlying mechanism of cortical network in DTi still remains unclear. This study aimed to investigate the regional brain activity and neural network changes during DTi induced by highly demanding cognitive-motor DT. Thirty-four right-handed healthy young adults performed the spiral-drawing task. They underwent a paced auditory serial addition test (PASAT) simultaneously or independently while their cortical activity was measured using functional near-infrared spectroscopy. Motor performance was determined using the balanced integration score (BIS), a balanced index of drawing speed and precision. The cognitive task of the PASAT was administered with two difficulty levels defined by 1 s (PASAT-1 s) and 2 s (PASAT-2 s) intervals, allowing for the serial addition of numbers. Cognitive performance was determined using the percentage of correct responses. These motor and cognitive performances were significantly reduced during DT, which combined a drawing and a cognitive task at either difficulty level, compared to those in the corresponding ST conditions. The DT conditions were also characterized by significantly increased activity in the right dorsolateral prefrontal cortex (DLPFC) compared to that in the ST conditions. Multivariate Granger causality (GC) analysis of cortical activity in the selected frontoparietal regions of interest further revealed selective top-down causal connectivity from the right DLPFC to the right inferior parietal cortex during DTs. Furthermore, changes in the frontoparietal GC connectivity strength between the PASAT-2 s DT and ST conditions significantly correlated negatively with changes in the percentage of correct responses. Therefore, DTi can occur even in cognitively proficient young adults, and the right DLPFC and frontoparietal network being crucial neural mechanisms underlying DTi. These findings provide new insights into DTi and its underlying neural mechanisms and have implications for the clinical utility of cognitive-motor DTs applied to clinical populations with cognitive decline, such as those with psychiatric and brain disorders.

The influence of travel time on perceived traveled distance varies by spatiotemporal scale.

The influence of travel time on perceived traveled distance has often been studied, but the results are inconsistent regarding the relationship between the two magnitudes. We argue that this is due to differences in the lengths of investigated travel distances and hypothesize that the influence of travel time differs for rather short compared to rather long traveled distances. We tested this hypothesis in a virtual environment presented on a desktop as well as through a head-mounted display. Our results show that, for longer distances, more travel time leads to longer perceived distance, while we do not find an influence of travel time on shorter distances. The presentation through an HMD vs. desktop only influenced distance judgments in the short distance condition. These results are in line with the idea that the influence of travel time varies by the length of the traveled distance, and provide insights on the question of how distance perception in path integration studies is affected by travel time, thereby resolving inconsistencies reported in previous studies.

Intravenous lipid emulsion interference in coagulation testing: an ex vivo analysis.

INTRODUCTION: Intravenous lipid emulsion is used in the rescue treatment of certain poisonings. A complication is interference with laboratory analyses. The aim of this study was to determine the impact of intravenous lipid emulsion on routine laboratory analysis of coagulation parameters ex vivo and determine if any of the analytical techniques remain reliable. METHODS: Samples were obtained from 19 healthy volunteers and divided in triplicate. One sample served as a control, and the other two were diluted to simulate the treatment of an average adult with Intralipid® 20 per cent Fresenius Kabi 100 mL (dilution-1) or 500 mL (dilution-2). Coagulation tests performed were prothrombin time, activated prothrombin time, D-dimer concentration and fibrinogen. Coagulation testing was performed by three techniques. Test-1 was performed on a Sysmex CN6000 analyzer. Test-2 was performed with a manual mechanical endpoint method using the semi-automated Stago KC4 Delta. Test-3 involved high-speed centrifugation before repeat testing on the Sysmex CN6000 analyzer. RESULTS: For test-1, only nine (47 per cent) samples in dilution-1 could be analyzed for coagulation tests, and no coagulation tests could be analyzed for dilution-2 because of lipaemia. For test-2 and test-3, all samples could be analyzed, and all results of both testing methods fell within the limits of the laboratory reference range. DISCUSSION: Difficulties in laboratory analysis of patients having received intravenous lipid emulsion are due to multiple factors. Most automated coagulation analyzers use optical measurements, which can be unreliable in the presence of a high intravenous lipid concentration. By altering the lipaemia in the testing solution using high-speed centrifugation or by using manual mechanical endpoint detection, we were able to obtain reliable results. These findings are limited by the use of an ex vivo method and healthy volunteers. CONCLUSIONS: This ex vivo model confirms that Intralipid® interferes with routine coagulation studies. It is important that clinicians are aware and inform their laboratories of its administration.

Therapeutic prostate cancer interventions: quantification of pubic arch interference and needle positioning errors.

INTRODUCTION: This study focuses on the quantification of and current guidelines on the hazards related to needle positioning in prostate cancer treatment: (1) access restrictions to the prostate gland by the pubic arch, so-called Pubic Arch Interference (PAI) and (2) needle positioning errors. Next, we propose solution strategies to mitigate these hazards. METHODS: The literature search was executed in the Embase, Medline ALL, Web of Science Core Collection*, and Cochrane Central Register of Controlled Trials databases. RESULTS: The literature search resulted in 50 included articles. PAI was reported in patients with various prostate volumes. The level of reported PAI varied between 0 and 22.3 mm, depending on the patient's position and the measuring method. Low-Dose-Rate Brachytherapy induced the largest reported misplacement errors, especially in the cranio-caudal direction (up to 10 mm) and the largest displacement errors were reported for High-Dose-Rate Brachytherapy in the cranio-caudal direction (up to 47 mm), generally increasing over time. CONCLUSIONS: Current clinical guidelines related to prostate volume, needle positioning accuracy, and maximum allowable PAI are ambiguous, and compliance in the clinical setting differs between institutions. Solutions, such as steerable needles, assist in mitigating the hazards and potentially allow the physician to proceed with the procedure.This systematic review was performed in accordance with the PRISMA guidelines. The review was registered at Protocols.io (DOI: dx.doi.org/10.17504/protocols.io.6qpvr89eplmk/v1).

Incremental RBF-based cross-tier interference mitigation for resource-constrained dense IoT networks in 5G communication system.

The deployment of resource-constrained and densely distributed Internet of Things (IoT) devices poses significant challenges for 5G communication systems due to the increased likelihood of inter-tier interference. This interference can degrade network performance and hinder the transmission of data in a reliable and efficient manner. Using an incremental Radial Basis Function (RBF) technique, this paper proposes a novel approach for cross-tier interference mitigation in 5G communication among resource-constrained dense IoT networks. Utilizing the incremental RBF method to model and optimize interference patterns in resource-constrained dense IoT networks is the primary innovation of our approach. In contrast to conventional interference mitigation techniques, which view interference as a static phenomenon, our method adapts to the dynamic nature of IoT networks by incrementally updating the RBF model. This enables precise modeling of the various interference scenarios and real-time modification of interference mitigation parameters. Utilizing the spatial distribution of IoT devices, this approach improves interference mitigation. The proposed method intelligently allocates resources and optimizes interference mitigation parameters based on the location and density of IoT devices. This adaptive resource allocation improves network capacity, reliability, and overall system performance by maximizing the utilization of available resources while minimizing interference. We demonstrate the effectiveness of the incremental RBF-based approach in mitigating cross-tier interference in resource-constrained dense IoT networks within the 5G ecosystem through extensive experiments and simulations. Our findings indicate substantial improvements in communication performance, including increased throughput, decreased packet loss, and decreased latency.

Effective target genes for RNA interference-based management of the cabbage stem flea beetle.

The cabbage stem flea beetle (CSFB, Psylliodes chrysocephala) is a key pest of oilseed rape. The ban on neonicotinoids in the European Union due to environmental concerns and the emergence of pyrethroid-resistant populations have made the control of CSFB extremely challenging. In search of a solution, we have recently shown that RNA interference (RNAi) has potential in the management of CSFB. However, the previously tested target genes for RNAi-mediated pest control (subsequently called target genes) exhibited moderate and slow-acting lethal effects. In this study, 27 double-stranded RNAs (dsRNAs) were orally delivered to identify highly effective target genes in CSFB adults by leveraging the findings of a genome-wide RNAi screen in Tribolium castaneum. Our screen using 500 ng of dsRNA identified 10 moderately effective (> 50% mortality) and 4 highly effective target genes (100% mortality in 8-13 days). The latter mainly included proteasome subunits. Gene expression measurements confirmed target gene silencing and dose-response studies revealed LD50 values as low as ~20 ng in 14 days following a single exposure to dsRNA. Four highly effective dsRNAs also inhibited leaf damage (up to ~75%) and one affected locomotion. The sequences of promising target genes were subjected to in silico target prediction in non-target organisms, for example, beneficials such as honeybees, to design environmentally friendly dsRNAs. Overall, the study provides valuable insights for the development of dsRNA-based insecticides against CSFB.

Automatic metaphor processing in developmental dyslexia.

INTRODUCTION: Previous research found metaphor impairments with dyslexia; however, it is unclear if difficulties are due to initial activation of the metaphorical meaning or to subsequent discourse integration processes. The study examines the presence of early automatic processing of metaphors in adults with developmental dyslexia, considering the role of executive functions and metaphor familiarity. METHODS: Using a sentence recall task and a semantic judgment task from the Metaphor Interference Effect (MIE) paradigm, we evaluated two early stages of metaphor comprehension, namely the generation of the figurative meaning and the suppression of the literal meaning. High and low familiar metaphors, and their scrambled counterparts, were aurally presented to participants, who were asked to judge whether sentences were literally true or literally false. Afterwards, they were provided ten minutes to recall the sentences they heard to verify the depth of processing for each type of stimulus. A total of 26 participants with dyslexia were included in the experimental group, and 31 in the control group. RESULTS: Individuals with dyslexia showed a MIE and an accuracy rate that are similar to participants without dyslexia. Inhibition correlated with the MIE size only for high familiar metaphors, and working memory seemed to play no role in the process. In the recall task, both groups demonstrated a better encoding of the metaphorical sentences compared to scrambled metaphors, but participants with dyslexia recalled less metaphors than did the control group, showing that metaphors are no exception to the limitations in sentence retrieval typically found in dyslexia. CONCLUSIONS: Our findings suggest that individuals with dyslexia are comparable to participants without dyslexia in their ability to automatically compute metaphorical meanings. Thus, difficulties in metaphor comprehension in people with dyslexia that have been detected in previous studies might depend on meaning construction in context rather than online semantic processing.

Polyglutamine Binding Protein 1 regulates neurite outgrowth through recruiting N-WASP.

Neurite outgrowth is a critical step in neural development, leading to the generation of neurite branches that allow individual neurons to make contacts with multiple neurons within the target region. Polyglutamine-binding protein 1 (PQBP1) is a highly conserved protein with a key role in neural development. Our recent mass spectrometric analysis showed that PQBP1 associates with neural Wiskott-Aldrich syndrome protein (N-WASP), an important actin polymerization-promoting factor involved in neurite outgrowth. Here, we report that the WW domain of PQBP1 directly interacts with the proline-rich domain of N-WASP. The disruption of this interaction leads to impaired neurite outgrowth and growth cone size. Furthermore, we demonstrate that PQBP1/N-WASP interaction is critical for the recruitment of N-WASP to the growth cone, but does not affect N-WASP protein levels or N-WASP-induced actin polymerization. Our results indicated that PQBP1 regulates neurite outgrowth by recruiting N-WASP to the growth cone, thus representing an alternative molecular mechanism via which PQBP1-mediates neurite outgrowth.

Spatiotemporally Controllable Covalent Bonding of RNA for Multi-Protein Interference.

Many diseases are associated with genetic mutation and expression of mutated proteins, such as cancers. Therapeutic approaches that selectively target the synthesis process of multiple proteins show greater potential compared to single-protein approaches in oncological diseases. However, conventional agents to regulate the synthesis of multiple protein still suffer from poor spatiotemporal selectivity and stability. Here, a new method using a dye-peptide conjugate, PRFK, for multi-protein interference with spatiotemporal selectivity and reliable stability, is reported. By using the peptide sequence that targets tumor cells, PRFK can be efficiently taken up, followed by specific binding to the KDELR (KDEL receptor) protein located in the endoplasmic reticulum (ER). The dye generates 1O2 under light irradiation, enabling photodynamic therapy. This process converts the furan group into a cytidine-reactive intermediate, which covalently binds to mRNA, thereby blocking protein synthesis. Upon treating 4T1 cells, the proteomics data show alterations in apoptosis, ferroptosis, proliferation, migration, invasion, and immune infiltration, suggesting that multi-protein interference leads to the disruption of cellular physiological activities, ultimately achieving tumor treatment. This study presents a multi-protein interference probe with the potential for protein interference within various subcellular organelles in the future.

The interference of anti-TSH autoantibody on clinical TSH detection.

Objective: It is well known that macro-thyroid-stimulating hormone (macro-TSH) could interfere with the detection of TSH. The anti-TSH autoantibody is an essential component of macro-TSH. However, the epidemiological characteristics and the clinical interference of the anti-TSH autoantibody are unclear. Methods: In this study, the radioimmunoprecipitation technique was used to detect the anti-TSH autoantibody. Platforms with different detection mechanisms were applied to measure the TSH in patients with the anti-TSH autoantibody. Polyethylene glycol (PEG) precipitation was used to determine the immunoassay interference. Results: The prevalence of the anti-TSH autoantibody in patients with mild subclinical hypothyroidism (SCH) and autoimmune thyroiditis, but normal thyroid function, was 4.78%. All 10 patients with anti-TSH antibodies had autoimmune diseases, with five of them having significant clinical test interference. Conclusion: The appearance of the anti-TSH antibody is not associated with thyroid autoantibodies. The presence of the anti-TSH autoantibody can interfere with the detection of TSH and can affect clinical diagnosis and treatment.

Assay Interference Causing Persistently Elevated Vancomycin Levels Leading to Treatment Failure and Fatal Outcome.

In patients receiving vancomycin therapy, serum drug levels are routinely monitored to ensure therapeutic dosing and minimize toxicity. In rare cases, vancomycin levels may be falsely or persistently elevated without any apparent cause. In this case report, we explore a rare case of persistently elevated vancomycin levels despite discontinuation of the drug for days.  This is a case of a 69-year-old female admitted for altered mental status secondary to sepsis from leg cellulitis. Antibiotic therapy included vancomycin. To ensure proper dosing, vancomycin trough levels were collected before the fourth dose, and the result showed a high value of 39 ug/ml. Vancomycin doses were adjusted as per the Bayesian dosing software, and the same remained to be in supratherapeutic levels. The patient eventually deteriorated, and due to persistently high vancomycin levels, the antibiotic regimen was switched to a different antibiotic. Despite normal renal functions, the vancomycin levels remained high, between 27 ug/ml and 32 ug/ml, even in the absence of any further doses. Subsequently, vancomycin serum concentration was determined by another method using high-performance liquid chromatography (HPLC). Blood cultures grew both coagulase-negative Staphylococcus aureus and Achromobacter xylosoxidans. Vancomycin levels remained high a week after discontinuation of the drug. Vancomycin by HPLC assay eventually showed that vancomycin was undetectable in the blood, but, unfortunately, the results came at a time when the patient had already expired. In conclusion, clinicians should maintain a high level of suspicion if persistently higher vancomycin levels cannot be accounted for by renal function or other causes. In patients with persistently high vancomycin levels who continue to clinically deteriorate, it is crucial to consider that assay interference can result in inaccurately elevated vancomycin levels.

Rewinding the Ratchet: Rare Recombination Locally Rescues Neo-W Degeneration and Generates Plateaus of Sex-Chromosome Divergence.

Natural selection is less efficient in the absence of recombination. As a result, nonrecombining sequences, such as sex chromosomes, tend to degenerate over time. Although the outcomes of recombination arrest are typically observed after many millions of generations, recent neo-sex chromosomes can give insight into the early stages of this process. Here, we investigate the evolution of neo-sex chromosomes in the Spanish marbled white butterfly, Melanargia ines, where a Z-autosome fusion has turned the homologous autosome into a nonrecombining neo-W chromosome. We show that these neo-sex chromosomes are likely limited to the Iberian population of M. ines, and that they arose around the time when this population split from North-African populations, around 1.5 million years ago. Recombination arrest of the neo-W chromosome has led to an excess of premature stop-codons and frame-shift mutations, and reduced gene expression compared to the neo-Z chromosome. Surprisingly, we identified two regions of ∼1 Mb at one end of the neo-W that are both less diverged from the neo-Z and less degraded than the rest of the chromosome, suggesting a history of rare but repeated genetic exchange between the two neo-sex chromosomes. These plateaus of neo-sex chromosome divergence suggest that neo-W degradation can be locally reversed by rare recombination between neo-W and neo-Z chromosomes.

Heterologous expression and characterization of two delta glutathione S-transferases genes involved in imidacloprid metabolism in Grapholita molesta.

Glutathione S-transferases (GSTs) are multifunctional enzymes, and insect GSTs play a pivotal role in the metabolism of insecticides. Grapholita molesta is a worldwide pest that causes substantial economic losses to the fruit industry. However, it remains unclear how imidacloprid, a commonly used insecticide in orchards, is metabolized by G. molesta. In the present study, the synergist diethyl maleate (DEM), which inhibits the GST activity, exhibited a 22-fold synergistic ratio against imidacloprid. Two new GST genes, GmGSTD2 (OR096251) and GmGSTD3 (OR096252), were identified and successfully cloned, showing the highest expression in the Malpighian tubes. Knockdown of GmGSTD2 and GmGSTD3 by RNA interference, increased the mortality of G. molesta from 28% to 47% following imidacloprid treatment. Both recombinant GmGSTD2 and GmGSTD3 proteins exhibited 1-chloro-2,4-dinitrobenzene (CDNB) activity and could be inhibited by imidacloprid in vitro, with maximum inhibition was 60% for GmGSTD2 and 80% for GmGSTD3. These results suggested that GSTs participate in the metabolism of imidacloprid with GmGSTD2 and GmGSTD3 playing key roles in this process.

Bacillus subtilis-derived peptides disrupt quorum sensing and biofilm assembly in multidrug-resistant Staphylococcus aureus.

Multidrug-resistant Staphylococcus aureus is one of the most clinically important pathogens in the world, with infections leading to high rates of morbidity and mortality in both humans and animals. The ability of S. aureus to form biofilms protects cells from antibiotics and promotes the transfer of antibiotic resistance genes; therefore, new strategies aimed at inhibiting biofilm growth are urgently needed. Probiotic species, including Bacillus subtilis, are gaining interest as potential therapies against S. aureus for their ability to reduce S. aureus colonization and virulence. Here, we search for strains and microbially derived compounds with strong antibiofilm activity against multidrug-resistant S. aureus by isolating and screening Bacillus strains from a variety of agricultural environments. From a total of 1,123 environmental isolates, we identify a single strain B. subtilis 6D1, with a potent ability to inhibit biofilm growth, disassemble mature biofilm, and improve antibiotic sensitivity of S. aureus biofilms through an Agr quorum sensing interference mechanism. Biochemical and molecular networking analysis of an active organic fraction revealed multiple surfactin isoforms, and an uncharacterized peptide was driving this antibiofilm activity. Compared with commercial high-performance liquid chromatography grade surfactin obtained from B. subtilis, we show these B. subtilis 6D1 peptides are significantly better at inhibiting biofilm formation in all four S. aureus Agr backgrounds and preventing S. aureus-induced cytotoxicity when applied to HT29 human intestinal cells. Our study illustrates the potential of exploring microbial strain diversity to discover novel antibiofilm agents that may help combat multidrug-resistant S. aureus infections and enhance antibiotic efficacy in clinical and veterinary settings. IMPORTANCE: The formation of biofilms by multidrug-resistant bacterial pathogens, such as Staphylococcus aureus, increases these microorganisms' virulence and decreases the efficacy of common antibiotic regimens. Probiotics possess a variety of strain-specific strategies to reduce biofilm formation in competing organisms; however, the mechanisms and compounds responsible for these phenomena often go uncharacterized. In this study, we identified a mixture of small probiotic-derived peptides capable of Agr quorum sensing interference as one of the mechanisms driving antibiofilm activity against S. aureus. This collection of peptides also improved antibiotic killing and protected human gut epithelial cells from S. aureus-induced toxicity by stimulating an adaptive cytokine response. We conclude that purposeful strain screening and selection efforts can be used to identify unique probiotic strains that possess specially desired mechanisms of action. This information can be used to further improve our understanding of the ways in which probiotic and probiotic-derived compounds can be applied to prevent bacterial infections or improve bacterial sensitivity to antibiotics in clinical and agricultural settings.

Trunk-Inspired SWCNT-Based Wrinkled Films for Highly-Stretchable Electromagnetic Interference Shielding and Wearable Thermotherapy.

Nowadays, the increasing electromagnetic waves generated by wearable devices are becoming an emerging issue for human health, so stretchable electromagnetic interference (EMI) shielding materials are highly demanded. Elephant trunks are capable of grabbing fragile vegetation and tearing trees thanks not only to their muscles but also to their folded skins. Inspired by the wrinkled skin of the elephant trunks, herein, we propose a winkled conductive film based on single-walled carbon nanotubes (SWCNTs) for multifunctional EMI applications. The conductive film has a sandwich structure, which was prepared by coating SWCNTs on both sides of the stretched elastic latex cylindrical substrate. The shrinking-induced winkled conductive network could withstand up to 200% tensile strain. Typically, when the stretching direction is parallel to the polarization direction of the electric field, the total EMI shielding effectiveness could surprisingly increase from 38.4 to 52.7 dB at 200% tensile strain. It is mainly contributed by the increased connection of the SWCNTs. In addition, the film also has good Joule heating performance at several voltages, capable of releasing pains in injured joints. This unique property makes it possible for strain-adjustable multifunctional EMI shielding and wearable thermotherapy applications.