Screening Of Interactions Research Articles

Lecanemab Planning: Blueprint for Safe and Effective Management of Complex Therapies.

Approximately 6.9 million American individuals have Alzheimer dementia and 50% have mild disease. Lecanemab, an approved antiamyloid antibody, is associated with modest reduction in functional decline in patients with mild dementia or mild cognitive impairment. In Clarity-AD, 239 (26.6%) of patients experienced amyloid-related imaging abnormalities (ARIAs) overall (i.e., ARIAs associated with hemorrhages or edema). The complexity of treatment and risks of adverse events necessitate a multidisciplinary collaborative approach. With limited treatment options, lecanemab approval generated significant interest among clinicians, patients, and families. Lecanemab treatment requires biweekly infusions along with ongoing imaging tests, laboratory monitoring, patient assessment, drug interaction screening, and cognitive function monitoring. Processes to support patient selection, access, and safety are important given the monitoring requirements and total cost of care. The planning process for lecanemab can serve as a blueprint to support safe and effective management of therapeutic innovation in neurology and other areas.

FATS inhibits the Wnt pathway and induces apoptosis through degradation of MYH9 and enhances sensitivity to paclitaxel in breast cancer.

Breast cancer is one of the most prevalent and diverse malignancies, and, with global cases increasing, the need for biomarkers to inform individual sensitivity to chemotherapeutics has never been greater. Our retrospective clinical analysis predicted that the expression of the fragile site-associated tumor suppressor (FATS) gene was associated with the sensitivity of breast cancer to neoadjuvant chemotherapy with paclitaxel. In vitro experiments subsequently demonstrated that FATS significantly increased the inhibitory effects of paclitaxel on breast cancer cells' migration, growth, and survival. An interaction screen revealed that FATS interacted with MYH9 and promoted its degradation via the ubiquitin-proteasome pathway, thereby downregulating Wnt signaling. By overexpressing FATS and MYH9, we demonstrated that FATS enhanced paclitaxel-induced apoptosis in breast cancer cells by degrading MYH9 to downregulate the Wnt pathway. We also demonstrated in a mouse xenograft model that FATS significantly increased the chemosensitivity of breast cancer cells to paclitaxel in vivo. This study presents a new mechanism by which FATS interacts with MYH9 to suppress the Wnt/β-catenin signaling pathway and induce apoptosis, thus enhancing the sensitivity of breast cancer cells to paclitaxel chemotherapy. The results also propose novel biomarkers for predicting breast cancer sensitivity to neoadjuvant chemotherapy with paclitaxel. Finally, we provide in vivo evidence that the combination of paclitaxel with IWR-1, a novel Wnt pathway inhibitor, synergistically suppresses breast cancer growth, laying the foundation for future trials with this drug combination. These results therefore provide a number of potential solutions for more precise treatment of patients with breast cancer in the future.

Fluids with power-law repulsion: Hyperuniformity and energy fluctuations.

We revisit the equilibrium statistical mechanics of a classical fluid of point-like particles with repulsive power-law pair interactions, focusing on density and energy fluctuations at finite temperature. Such long-range interactions, decaying with inter-particle distance $r$ as $1/r^s$ in $d$ dimensions, are known to fall into two qualitatively different categories. For $s<d$ (``strongly" long-range interactions) there are screening of correlations and suppression of large-wavelength density fluctuations (hyperuniformity). These effects eliminate density modes with arbitrarily large energy. For $s>d$ (``weakly" long-range interactions) screening and hyperuniformity do not occur. Using scaling arguments, variational analysis, and Monte Carlo simulations, we find another qualitative distinction. For $s\geq d/2$ the strong repulsion at short distances leads to enhanced small-wavelength density fluctuations, decorrelating particle positions. This prevents indefinitely negative entropy and large energy fluctuations. The distinct behaviors for $s\geq d/2$ and $s<d/2$ give rise to qualitatively different dependencies of the entropy, heat capacity, and energy fluctuations on temperature and density. We investigate the effect of introducing an upper cutoff distance in the pair-potential. The effect of the cutoff on energy fluctuations is strong for $s<d/2$ and negligible for $s \geq d/2$.

A comprehensive two-hybrid analysis to explore the Legionella pneumophila effector-effector interactome.

Secreted bacterial effector proteins are typically viewed as modulators of host activity, entering the host cytosol to physically interact with and modify the activity of one or more host proteins in support of infection. A growing body of evidence suggests that a subset of effectors primarily function to modify the activities of other effectors inside the host. These "effectors of effectors" or metaeffectors are often identified through experimental serendipity during the study of canonical effector function against the host. We previously performed the first global effector-wide genetic interaction screen for metaeffectors within the arsenal of Legionella pneumophila, an intracellular bacterial pathogen with over 300 effectors. Here, using a high-throughput, scalable methodology, we present the first global interaction network of physical interactions between L. pneumophila effectors. This data set serves as a complementary resource to identify and understand both the scope and nature of non-canonical effector activity within this important human pathogen.

Influence of dynamical screening of four-quarks interaction on the chiral phase diagram

We investigate the effect of screening of the four-quarks contact interactions by the ring diagram at finite temperature and density in an effective chiral model inspired by QCD in the Coulomb gauge. As a consequence, a medium-dependent coupling naturally emerges which, in a class of chiral models, brings the chiral crossover temperature down to the value calculated in lattice QCD at low net-baryon density. Furthermore, it implies a stronger divergence of the chiral susceptibility at the critical point compared to the mean-field dynamics. At high densities, the screening induces a substantial instability region and its size depends on the regularization schemes. We discuss the properties of an effective potential for a class of models described by momentum-independent gap equations. In particular, we introduce the method to construct an approximate effective potential from the gap equations to determine the location of the first-order phase transition. Published by the American Physical Society 2024

Zinc finger transcription factors BnaSTOP2s regulate sulfur metabolism and confer Sclerotinia sclerotiorum resistance in Brassica napus.

Rapeseed (Brassica napus L.) exhibits high-sulfur requirements to achieve optimal growth, development, and pathogen resistance. Despite the importance of sulfur, the mechanisms regulating its metabolism and disease resistance are not fully understood. In this study, we found that the zinc finger transcription factors BnaSTOP2s play a pivotal role in sulfur metabolism and Sclerotinia sclerotiorum resistance. Our findings indicate that BnaSTOP2s are involved in sulfur metabolism, as evidenced by extensive protein interaction screening. BnaSTOP2s knockout reduced the content of essential sulfur-containing metabolites, including glucosinolate and glutathione, which is consistent with the significantly lowered transcriptional levels of BnaMYB28s and BnaGTR2s, key factors involved in glucosinolate synthesis and transportation, respectively. Comprehensive RNA-seq analysis revealed the substantial effect of BnaSTOP2s on sulfur metabolism from roots to siliques, which serve as pivotal sources and sinks for sulfur metabolism, respectively. Furthermore, we found that leaf lesion size significantly decreased and increased in the BnaSTOP2-OE and Bnastop2 mutants, respectively, compared with the wild-type during S. sclerotiorum infection, suggesting a vital role of BnaSTOP2s in plant defense response. In conclusion, BnaSTOP2s act as global regulators of sulfur metabolism and confer resistance to S. sclerotiorum infection in B. napus. Thus, they have potential implications for improving crop resilience.

Device to Measure, Monitor and Control Variables for Agricultural Purposes

The measurement of meteorological variables is important for decision-making in the field. Accurate data can help farmers optimize their activities to improve food production. Traditional methods of monitoring variables can be expensive or complex for small-scale farmers to use. This indicates a need for low-cost and user-friendly devices. Currently, there is technology for developing these types of devices, which could be useful to automate processes based on variable monitoring and improve food production. Due to this, a device based on the Arduino Mega&amp;lt;SUP&amp;gt;TM&amp;lt;/SUP&amp;gt; board was developed to monitor air temperature, relative humidity, rain, and soil moisture. In addition, equipment was developed to be controlled based on a rain gauge. The device has a TFT touch screen for easy-user interaction and 4 menus for information display (summary, floor, date-time and manual equipment control). The program of the device required more lines of code (59.65%) to establish user-device interaction compared to its internal processes (18.66%) and variable declarations (21.68%). A container was 3D printed to house all the integrated circuits and the device was tested under both indoor (Jun-10, 2024 to July-17, 2024) and outdoor (Jul-22, 2024 to Aug-18, 2024) conditions. Under indoor conditions, a 3% difference was found in the temperature measurements taken under the same conditions (using DS18B20 and MLX90614 sensors). Under outdoor conditions it was found that the air temperature decreased by an average of 2.33°C when increasing the height from 8ft to 16ft and the relative humidity decreased by an average 3.48% when increasing the height from 8ft to 16ft. There was a 3.4% difference in total rain measured by the rain gauges. Finally, the developed device performed adequately during the two months of testing in both conditions, measuring variables and controlling equipment (the equipment went from waiting mode to rain harvesting mode 92 times).

Molecular Simulations of Thermal Transport across Iron Oxide-Hydrocarbon Interfaces.

The rational design of dielectric fluids for immersion cooling of batteries requires a molecular-level understanding of the heat flow across the battery casing/dielectric fluid interface. Here, we use nonequilibrium molecular dynamics (NEMD) simulations to quantify the interfacial thermal resistance (ITR) between hematite and poly-α-olefin (PAO), which are representative of the outer surface of the steel battery casing and a synthetic hydrocarbon dielectric fluid, respectively. After identifying the most suitable force fields to model the thermal properties of the individual components, we then compared different solid-liquid interaction potentials for the calculation of the ITR. These potentials resulted in a wide range of ITR values (4-21 K m2 GW-1), with stronger solid-liquid interactions leading to lower ITR. The increase in ITR is correlated with an increase in density of the fluid layer closest to the surface. Since the ITR has not been experimentally measured for the hematite/PAO interface, we validate the solid-liquid interaction potential using the work of adhesion calculated using the dry-surface method. The work of adhesion calculations from the simulations were compared to those derived from experimental contact angle measurements for PAO on steel. We find that all of the solid-liquid potentials overestimate the experimental work of adhesion. The experiments and simulations can only be reconciled by further reducing the strength of the interfacial interactions. This suggests some screening of the solid-liquid interactions, which may be due to the presence of an interfacial water layer between PAO and steel in the contact angle experiments. Using the solid-liquid interaction potential that reproduces the experimental work of adhesion, we obtain a higher ITR (33 K m2 GW-1), suggesting inefficient thermal transport. The results of this study demonstrate the potential for NEMD simulations to improve understanding of the nanoscale thermal transport across industrially important interfaces. This study represents an important step toward the rational design of more effective fluids for immersion cooling systems for electric vehicles and other applications where thermal management is of high importance.

Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling

Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition.

Potential drug-drug interactions and associated factors among hospitalized pediatric patients in Adigrat general hospital, Tigrai, north Ethiopia: a retrospective cross-sectional study

BackgroundDrug-drug interactions (DDIs) are associated with increased or decreased adverse effects and decreased or decreased therapeutic effects. Hospitalized pediatric patients are exposed to a number of potential DDIs (pDDIs). There are limited studies on pDDIs among pediatric patients in Ethiopia. This study was aimed to evaluate the pDDIs and associated factors among hospitalized pediatric patients in Adigrat general hospital, Tigrai, northern Ethiopia.MethodsA retrospective cross-sectional study was carried out among hospitalized pediatric patients in Adigrat general hospital from 01 July 2020 to 31 August 2020. A simple random sampling technique was used to select medical charts. Micromedex 2.0 database was used to screen pDDIs. Data was analyzed using statistical package for social science version 21 and a P-value of ≤ 0.05 was considered statistically significant.ResultsOf the total 146 patients studied, 100 (68.5%) were exposed for at least one pDDI. A total of 158 pDDIs consisting of 33 distinct interacting drug pairs were identified. About 19.3% of the patients had at least one major pDDI, 6.7% at least one moderate and 68.9% at least one minor pDDIs. On the other hand, 63.3% of the total pDDIs were minor and 25.9% major while 3. 8% were contraindicated pDDIs with 15.2% fair and 81.6% good level of documentation. The overall mean duration of pDDIs exposure was about 4.9 (1-23) days. The frequently occurring potential clinical consequences of pDDIs comprised increased risk of QT-interval prolongation (10.1%), theophylline toxicity (5.1%), antiepileptic toxicity (5.1%) and formation of ceftriaxone calcium precipitates (3.8%). Infant/toddler age group (adjusted odds ratio [AOR] = 31.961, 95% CI: 1.117-914.528), number of diseases (AOR = 0.255, 95% CI: 0.069-0.939) and polypharmacy (AOR = 0.276, 95% CI: 0.091-0.838) were associated with pDDIs exposures.ConclusionsA large number of pediatric patients were exposed to a various pDDIs. Age, number of diseases and polypharmacy predicted for the occurrence of pDDIs. Besides, the major severity pDDIs encounted frequently in the current study can potentially lead to a life threatening cardio-vascular toxicicty from QT-interval prolongation. Clinicians should be vigilant to pDDIs to prevent potential clinical consequences of pDDIs. Moreover, computerized drug interaction screening and clincal pharmacy services should be practiced to improve patients’ safety.

The lysosomal lipid transporter LIMP-2/SCARB2 is part of lysosome-endoplasmic reticulum STARD3-VAPB-dependent contact sites.

SCARB2/LIMP-2 is an abundant lysosomal membrane protein. Previous studies have shown LIMP-2 functions as a virus receptor, a chaperone for lysosomal enzyme targeting, and a lipid transporter. The large luminal domain of LIMP-2 contains a hydrophobic tunnel that enables transport of phospholipids, sphingosine and cholesterol from the lysosomal lumen to the membrane. The question about the fate of the lipids after LIMP-2-mediated transport is largely unexplored. To elucidate whether LIMP-2 is part of contact sites between lysosomes and the endoplasmic reticulum (ER), we performed a proximity-based interaction screen. This revealed that LIMP-2 interacts with the endosomal protein STARD3 and the ER-resident protein VAPB. Using imaging and co-immunoprecipitation, we demonstrated colocalization and physical interaction between LIMP-2 and these proteins. Moreover, we found that interaction of LIMP-2 with VAPB required the presence of STARD3. Our findings suggest that LIMP-2 is part of ER-lysosome contact sites, possibly facilitating cholesterol transport from the lysosomal to the ER membrane. This suggests a novel mechanism for inter-organelle communication and lipid trafficking mediated by LIMP-2.

Effectively Sieving Alkali Metal Ions Using Functionalized Graphene Oxide Membranes by Exploiting Water-Repellent Interactions.

Sieving membranes capable of discerning different alkali metal ions are important for many technologies, such as energy, environment, and life science. Recently, two-dimensional (2D) materials have been extensively explored for the creation of sieving membranes with angstrom-scale channels. However, because of the same charge and similar hydrated sizes, mostly laminated membranes typically show low selectivity (<10). Herein, we report a facile and scalable method for functionalizing graphene oxide (GO) laminates by dually grafting cations and water-repellent dimethylsiloxane (DMDMS) molecules to achieve high selectivities of ∼50 and ∼20 toward the transport of Cs+/Li+ and K+/Li+ ion pairs, surpassing many of the state-of-the-art laminated membranes. The enhanced selectivity for alkali metal ions can be credited to a dual impact: (i) strong hydrophobic interactions between the incident cations' hydration shells and the water-repellent DMDMS; (ii) the efficient screening of electrostatic interactions that hamper selectivity.

Digital screener of socio-motor agency balancing motor autonomy and motor control.

Dyadic social interactions evoke complex dynamics between two agents that, while exchanging unequal levels of body autonomy and motor control, may find a fine balance to synergize, take turns, and gradually build social rapport. To study the evolution of such complex interactions, we currently rely exclusively on subjective pencil and paper means. Here, we complement this approach with objective biometrics of socio-motor behaviors conducive to socio-motor agency. Using a common clinical test as the backdrop of our study to probe social interactions between a child and a clinician, we demonstrate new ways to streamline the detection of social readiness potential in both typically developing and autistic children by uncovering a handful of tasks that enable quantification of levels of motor autonomy and levels of motor control. Using these biometrics of autonomy and control, we further highlight differences between males and females and uncover a new data type amenable to generalizing our results to any social setting. The new methods convert continuous dyadic bodily biorhythmic activity into spike trains and demonstrate that in the context of dyadic behavioral analyses, they are well characterized by a continuous Gamma process that can classify individual levels of our thus defined socio-motor agency during a dyadic exchange. Finally, we apply signal detection processing tools in a machine learning approach to show the validity of the streamlined version of the digitized ADOS test. We offer a new framework that combines stochastic analyses, non-linear dynamics, and information theory to streamline and facilitate scaling the screening and tracking of social interactions with applications to autism.

Identification of NET formation and the renoprotective effect of degraded NETs in lupus nephritis.

To explore molecular biomarkers associated with the pathophysiology and therapy of lupus nephritis (LN), we conducted a joint analysis of transcriptomic data from 40 peripheral blood mononuclear cells (PBMCs) (GSE81622) and 21 kidney samples (GSE112943) from the Gene Expression Omnibus database using bioinformatics. A total of 976 and 2,427 differentially expressed genes (DEGs) were identified in PBMCs and renal tissues. Seven and two functional modules closely related to LN were identified. Further enrichment analysis revealed that the neutrophil activation pathway was highly active in both PBMCs and the kidney. Subsequently, 16 core genes closely associated with LN were verified by protein-protein interaction screening and quantitative PCR. In vitro cell models and MRL/lpr mouse models confirmed that the abnormal expression of these core genes was closely linked to neutrophil extracellular traps (NETs) generated by neutrophil activation, while degradation of NETs led to downregulation of core gene expression, thereby improving pathological symptoms of LN. Therefore, identification of patients with systemic lupus erythematosus exhibiting abnormal expression patterns for these core genes may serve as a useful indicator for kidney involvement. In addition, targeting neutrophils to modulate their activation levels and inhibit aberrant expression of these genes represents a potential therapeutic strategy for treating LN. NEW & NOTEWORTHY The mechanisms by which immune cells cause kidney injury in lupus nephritis are poorly understood. We integrated and analyzed the transcriptomic features of PBMCs and renal tissues from the GEO database to identify key molecular markers associated with neutrophil activation. We confirmed that neutrophil extracellular traps (NETs) formed by neutrophil activation promoted the upregulation of key genes in cell and animal models. Targeted degradation of NETs significantly ameliorated kidney injury in MRL/lpr mice.

CRISPR screens unveil nutrient-dependent lysosomal and mitochondrial nodes impacting intestinal tissue-resident memory CD8+ T cell formation

Nutrient availability and organelle biology direct tissue homeostasis and cell fate, but how these processes orchestrate tissue immunity remains poorly defined. Here, using invivo CRISPR-Cas9 screens, we uncovered organelle signaling and metabolic processes shaping CD8+ tissue-resident memory T (TRM) cell development. TRM cells depended on mitochondrial translation and respiration. Conversely, three nutrient-dependent lysosomal signaling nodes-Flcn, Ragulator, and Rag GTPases-inhibited intestinal TRM cell formation. Depleting these molecules or amino acids activated the transcription factor Tfeb, thereby linking nutrient stress to TRM programming. Further, Flcn deficiency promoted protective TRM cell responses in the small intestine. Mechanistically, the Flcn-Tfeb axis restrained retinoic acid-induced CCR9 expression for migration and transforming growth factor β (TGF-β)-mediated programming for lineage differentiation. Genetic interaction screening revealed that the mitochondrial protein Mrpl52 enabled early TRM cell formation, while Acss1 controlled TRM cell development under Flcn deficiency-associated lysosomal dysregulation. Thus, the interplay between nutrients, organelle signaling, and metabolic adaptation dictates tissue immunity.

Genome-Wide and Transcriptome-Wide Association Studies on Northern New England and Ohio Amyotrophic Lateral Sclerosis Cohorts.

Amyotrophic lateral sclerosis (ALS) is an age-associated, fatal neurodegenerative disorder causing progressive paralysis and respiratory failure. The genetic architecture of ALS is still largely unknown. We performed a genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) to understand genetic risk factors for ALS using a population-based case-control study of 435 ALS cases and 279 controls from Northern New England and Ohio. Single nucleotide polymorphism (SNP) genotyping was conducted using the Illumina NeuroChip array. Odds ratios were estimated using covariate-adjusted logistic regression. We also performed a genome-wide SNP-smoking interaction screening. TWAS analyses used PrediXcan to estimate associations between predicted gene expression levels across 15 tissues (13 brain tissues, skeletal muscle, and whole blood) and ALS risk. GWAS analyses identified the p.A382T missense variant (rs367543041, p = 3.95E-6) in the TARDBP gene, which has previously been reported in association with increased ALS risk and was found to share a close affinity with the Sardinian haplotype. Both GWAS and TWAS analyses suggested that ZNF235 is associated with decreased ALS risk. Our results support the need for future evaluation to clarify the role of these potential genetic risk factors for ALS and to understand genetic susceptibility to environmental risk factors.

Ultrasensitive and multiplexed Gastric cancer biomarkers detection with an integrated electrochemical immunosensing platform

Developing immunosensing platforms capable of simultaneously detecting multiple cancer markers is crucial for clinical diagnosis and biomedical research. Here, we introduce a novel dual-mode electrochemical biosensing assay platform capable of detecting two gastric cancer biomarkers: pepsinogen I (PG I) and pepsinogen II (PG II). Methylene blue (MB) and Prussian blue (PB) were used as dual signal sources to label PG I and PG II, respectively. The platform integrates an ARM STM32F411 microcontroller and an AD5941 analog front-end, which not only facilitates cyclic voltammetry (CV) and differential pulse voltammetry (DPV) with efficacy comparable to commercial electrochemical workstations but also offers data collection and synchronous analysis capabilities, allowing simultaneous output of PG I and PGR (PG I/PG II) values. Equipped with an interactive screen for operational control and result display, the immunosensing platform provides linear detection ranges for PG I (5 pg/mL–100 ng/mL) and PG II (50 pg/mL–200 ng/mL), enabling rapid detection within 5 min. It demonstrates excellent sensitivity and selectivity when comparing serum samples from healthy individuals and gastric cancer patients. The dual-marker detection platform significantly enhances early diagnosis and screening of gastric cancer, offering substantial improvements over single-marker assays. Furthermore, this platform shows potential for detecting multiple biomarkers in various diseases, highlighting its utility for biomedical applications.

Droplet-based functional CRISPR screening of cell-cell interactions by SPEAC-seq.

Cell-cell interactions are essential for the function and contextual regulation of biological tissues. We present a platform for high-throughput microfluidics-supported genetic screening of functional regulators of cell-cell interactions. Systematic perturbation of encapsulated associated cells followed by sequencing (SPEAC-seq) combines genome-wide CRISPR libraries, cell coculture in droplets and microfluidic droplet sorting based on functional read-outs determined by fluorescent reporter circuits to enable the unbiased discovery of interaction regulators. This technique overcomes limitations of traditional methods for characterization of cell-cell communication, which require a priori knowledge of cellular interactions, are highly engineered and lack functional read-outs. As an example of this technique, we describe the investigation of neuroinflammatory intercellular communication between microglia and astrocytes, using genome-wide CRISPR-Cas9 inactivation libraries and fluorescent reporters of NF-κB activation. This approach enabled the discovery of thousands of microglial regulators of astrocyte NF-κB activation important for the control of central nervous system inflammation. Importantly, SPEAC-seq can be adapted to different cell types, screening modalities, cell functions and physiological contexts, only limited by the ability to fluorescently report cell functions and by droplet cultivation conditions. Performing genome-wide screening takes less than 2 weeks and requires microfluidics capabilities. Thus, SPEAC-seq enables the large-scale investigation of cell-cell interactions.

MTS-YOLO: A Multi-Task Lightweight and Efficient Model for Tomato Fruit Bunch Maturity and Stem Detection

The accurate identification of tomato maturity and picking positions is essential for efficient picking. Current deep-learning models face challenges such as large parameter sizes, single-task limitations, and insufficient precision. This study proposes MTS-YOLO, a lightweight and efficient model for detecting tomato fruit bunch maturity and stem picking positions. We reconstruct the YOLOv8 neck network and propose the high- and low-level interactive screening path aggregation network (HLIS-PAN), which achieves excellent multi-scale feature extraction through the alternating screening and fusion of high- and low-level information while reducing the number of parameters. Furthermore, We utilize DySample for efficient upsampling, bypassing complex kernel computations with point sampling. Moreover, context anchor attention (CAA) is introduced to enhance the model’s ability to recognize elongated targets such as tomato fruit bunches and stems. Experimental results indicate that MTS-YOLO achieves an F1-score of 88.7% and an mAP@0.5 of 92.0%. Compared to mainstream models, MTS-YOLO not only enhances accuracy but also optimizes the model size, effectively reducing computational costs and inference time. The model precisely identifies the foreground targets that need to be harvested while ignoring background objects, contributing to improved picking efficiency. This study provides a lightweight and efficient technical solution for intelligent agricultural picking.

Probing the interplay of interactions, screening and strain in monolayer MoS2 via self-intercalation

Controlling many-body interactions in two-dimensional systems remains a formidable task from the perspective of both fundamental physics and application. Here, we explore remarkable electronic structure alterations of MoS2 monolayer islands on graphene on Ir(111) induced by non-invasive self-intercalation. This introduces significant differences in morphology and strain of MoS2 as a result of the modified interaction with the substrate. Consequently, considerable changes of the band gap and non-rigid electronic shifts of valleys are detected, which are a combined effect of the screening of the many-body interactions and strain in MoS2. Furthermore, theory shows that each substrate leaves a unique stamp on the electronic structure of two-dimensional material in terms of those two parameters, restricted by their correlation.