[Identification and expression profiling of SAPK gene family members in Dendrobium officinale].

To investigate the potential roles of stress-activated protein kinase (SAPK) gene family members in Dendrobium officinale, we employed multiple bioinformatics methods to identify the members of this family. The physicochemical properties, chromosomal localization, phylogenetic relationship, gene structure, and cis-acting elements of each D. officinale SAPK (DoSAPK) member were analyzed. In addition, their expression profiles in different tissues and under the low-temperature or salt stress treatment were determined by real-time fluorescence quantitative PCR. The results showed that D. officinale carried eight DoSAPK family members, which belonged to three groups (groups Ⅰ, Ⅱ, and Ⅲ). These genes were located on seven chromosomes, and there were two pairs of genes with replication. The DoSAPK members within the same group had similar gene structures, conserved motifs, and secondary structures. The cis-acting elements in the promoter regions of DoSAPK genes included abundant hormone and stress response elements. DoSAPK family members presented tissue-specific expression in D. officinale. Furthermore, they were differentially expressed under the low-temperature or salt stress treatment, which suggested that they might be involved in the responses to low-temperature and salt stress. Intriguingly, DoSAPK1 might play a role in the abiotic stress responses. The results laid a foundation for in-depth study of the members and roles of the DoSAPK gene family.

Audience segmentation approach to conservation messaging for transforming the exotic pet trade.

Advancing transformative change for sustainability requires population-wide behavior change. Yet, many behavioral interventions tackling environmental problems only examine average effects on the aggregate, overlooking the heterogeneous effects in a population. We developed and preregistered a novel audience segmentation approach to test the diverse impact of conservation messaging on reducing demand for exotic pets (private action - i.e., desire to own exotic pets or visit wildlife entertainment places) and fostering citizen engagement for system-wide change (civic action - e.g., signing a petition or participating in a protest against the exotic pet trade). Through an online survey with US participants (n = 2953), we identified 4 population segments (early adopters, early majority, late majority, and laggards), representing varying levels of commitment to wildlife conservation and then randomly assigned each segment to one of 3 messaging conditions. Messages highlighting negative consequences of the exotic pet trade and the power of collective action for system change effectively promoted private action among all segments except early adopters (ηp 2 = 0.005). Among civic actions, only the collective action message motivated early adopters and the early majority to sign petitions (φC = 0.193 and φC = 0.097, respectively). Furthermore, the 4 segments showed distinct reasoning for action and inaction on wildlife conservation, with certain relational values, such as care, serving as both motivations and barriers to action. These findings highlight the need for targeted behavioral interventions across diverse populations.

Estrategia de segmentación del público en los mensajes de conservación para transformar el mercado de mascotas exóticas Resumen El progreso en el cambio transformativo para la sustentabilidad requiere de cambios conductuales a nivel poblacional. Sin embargo, muchas intervenciones conductuales que abordan los problemas ambientales sólo analizan los efectos promedio sobre el agregado, lo que ignora los efectos heterogéneos sobre la población. Desarrollamos y preinscribimos una estrategia novedosa de segmentación del público para evaluar los diversos impactos de los mensajes de conservación sobre la reducción de la demanda de mascotas exóticas (acción privada [es decir, el deseo de poseer mascotas exóticas o visitar sitios de entretenimiento con fauna] y promover la participación ciudadana para un cambio sistémico [por ejemplo, firmar una petición o participar en una protesta contra el mercado de mascotas exóticas]). Realizamos una encuesta en línea con participantes estadunidenses (n = 2953) para identificar cuatro segmentos de la población (adoptadores tempranos, mayoría temprana, mayoría tardía y rezagados), los cuales representan diferentes niveles de compromiso con la conservación de fauna, y después le asignamos aleatoriamente a cada segmento una de las siguientes condiciones de mensaje: las consecuencias negativas del mercado de mascotas exóticas, el poder de la acción colectiva para el cambio sistémico e información neutral como control. Los mensajes que resaltaban las consecuencias negativas del mercado de mascotas exóticas y el poder de la acción colectiva promovieron de forma eficiente la acción privada en todos los segmentos excepto los adoptadores tempranos (ηp 2 = 0.005). Entre las acciones cívicas, sólo el mensaje de acción colectiva motivó a los adoptadores tempranos y a la mayoría temprana a firmar peticiones (φC = 0.193 y φC = 0.097, respectivamente). Además, los cuatro segmentos mostraron un razonamiento distinto para la acción e inacción para la conservación de fauna, con ciertos valores de relación, como el cuidado, fungiendo como motivación o barreras para la acción. Estos resultados enfatizan la necesidad de tener intervenciones conductuales focalizadas entre las diferentes poblaciones.

[Research progress on the neural mechanism of the regulation of social isolation on innate behaviors].

Innate behavior is mainly controlled by genetics, but is also regulated by social experiences such as social isolation. Studies in animal models such as Drosophila and mice have found that social isolation can regulate innate behaviors through the changes at the molecular level, such as hormone, neurotransmitter, neuropeptide level, and at the level of neural circuits. In this review, we summarized the research progress on the regulation of social isolation on various animal innate behaviors, such as sleep, reproduction and aggression by altering the expression of conserved neuropeptides and neurotransmitters, hoping to deepen the understanding of the key and conserved signal pathways that regulate innate behavior by social isolation.

Naodesheng decoction regulating vascular function via G-protein-coupled receptors: network analysis and experimental investigations.

Introduction: Ischemic stroke (IS) is a detrimental neurological disease with limited treatment options. Recanalization of blocked blood vessels and restoring blood supply to ischemic brain tissue are crucial for post-stroke rehabilitation. The decoction Naodesheng (NDS) composed of five Chinese botanical drugs, including Panax notoginseng (Burk.) F. H. Chen, Ligusticum chuanxiong Hort., Carthamus tinctorius L., Pueraria lobata (Willd.) Ohwi, and Crataegus pinnatifida Bge., is a blood-activating and stasis-removing herbal medicine commonly used for the clinical treatment of cerebrovascular diseases in China. However, the material basis of NDS on the effects of blood circulation improvement and vascular tone regulation remains unclear. Methods: A database comprising 777 chemical metabolites of NDS was constructed. Then, the interactions between various herbal metabolites of NDS and five vascular tone modulation G-protein-coupled receptors (GPCRs), including 5-HT1AR, 5-HT1BR, ß2-AR, AT1R, and ETBR, were assessed by molecular docking. Using network analysis and vasomotor experiment of the cerebral basilar artery, the potential material basis underlying the vascular regulatory effects of NDS was further explored. Results: The Naodesheng Effective Component Group (NECG) was found to induce relaxation of rat basilar artery rings precontracted using Endothelin-1 (ET-1) and KCl in vitro in a dose-dependent manner. Several metabolites of NDS, including C. tinctorius, C. pinnatifida, and P. notoginseng, were found to be the main plant resources of metabolites with high docking scores. Furthermore, several metabolites in NDS, including formononetin-7-glucoside, hydroxybenzoyl-coumaric anhydride, methoxymecambridine, puerarol, and pyrethrin II, were found to target multiple vascular GPCRs. Metabolites with moderate-to-high binding energy were verified to have good rat basilar artery-relaxing effects, and the maximum artery relaxation effects of all three metabolites, namely, isorhamnetin, kaempferol, and daidzein, were found to exceed 90%. Moreover, metabolites of NDS were found to exert a synergistic effect by interacting with vascular GPCR targets, and these metabolites may contribute to the cerebrovascular regulatory function of NDS. Discussion: The study reports that various metabolites of NDS contribute to its vascular tone regulating effects and demonstrates the multi-component and multi-target characteristics of NDS. Among them, metabolites with moderate-to-high binding scores in NDS may play an important role in regulating vascular function.

Fe Single-Atom Carbon Dots Nanozyme Collaborated with Nucleic Acid Exonuclease III-Driven DNA Walker Cascade Amplification Strategy for Circulating Tumor DNA Detection.

Circulating tumor DNA (ctDNA), as a next-generation tumor marker, enables early screening and monitoring of cancer through noninvasive testing. Exploring the development of new methods for ctDNA detection is an intriguing study. In this work, a unique electrochemical biosensor for the ctDNA detector was constructed in the first utilizing Fe single-atom nanozymes-carbon dots (SA Fe-CDs) as a signaling carrier in collaboration with a DNA walker cascade amplification strategy triggered by nucleic acid exonuclease III (Exo III). The electrochemical active surface area of AuNPs/rGO modified onto a glassy carbon electrode (AuNPs/rGO/GCE) was about 1.43 times that of a bare electrode (bare GCE), with good electrical conductivity alongside a high heterogeneous electron transfer rate (5.81 × 10-3 cm s-1), that is, as well as the ability to load more molecules. Sequentially, the DNA walker cascade amplification strategy driven by Exo III effectively converted the target ctDNA into an amplified biosignal, ensuring the sensitivity and specificity of ctDNA. Ultimately, the electrochemical signal was further amplified by introducing SA Fe-CDs nanozymes, which could serve as catalysts for 3,3',5,5'-tetramethylbenzidine (TMB) oxidation with facile responding (Vmax = 0.854 × 10-6 M s-1) and robust annexation (Km = 0.0069 mM). The integration of the triple signal amplification approach achieved detection limits as low as 1.26 aM (S/N = 3) for a linearity spanning from 5 aM to 50 nM. In this regard, our proposal for a biosensor with exceptional assay properties in complicated serum environments had great potential for early and timely diagnosis of cancer.

Pattern-based colorimetric sensor array chip for discrimination of Baijiu aromas.

Gas mixtures are comprised of numerous complex components, making the accurate identification a continuing challenge due to the significant limitations of existing detection methods. Herein, we developed a low-cost and sensitive pattern-based colorimetric sensor array chip for the identification of typical gas mixtures - Baijiu aroma. Specifically, three nanomaterials (AuNPs, MoS2 and ZIF-8) were prepared to adsorb gas molecules and enhance the reaction of trace gases with sensor arrays. The colorimetric sensor array chip took only 5 min to complete the recognition of Baijiu aromas and effectively avoided recognition errors caused by sommelier olfactory fatigue. Notably, the hierarchical cluster analysis (HCA) revealed no confusion or errors in the results of 80 tests across the five trials involving 16 commercial Baijius. Even fake Baijius with similar ingredients could be easily identified, demonstrating the excellent analytical capabilities of the system in Baijiu identification and its significant potential for quality control of Baijius.

Effects of polyethylene, polylactic acid, and tire particles on the sediment microbiome and metabolome at high and low temperatures.

Global warming has led to a high incidence of extreme heat events, and the frequent occurrence of extreme heat events has had extensive and far-reaching impacts on wetland ecosystems. The widespread distribution of plastics in the environment, including polyethylene (PE), polylactic acid (PLA), and tire particles (TPs), has caused various environmental problems. Here, high-throughput sequencing techniques and metabolomics were used for the first time to investigate the effects of three popular microplastic types: PE, PLA, and TP, on the sediment microbiome and the metabolome at both temperatures. The microplastics were incorporated into the sediment at a concentration of 3% by weight of the dry sediment (wt/wt), to reflect environmentally relevant conditions. Sediment enzymatic activity and physicochemical properties were co-regulated by both temperatures and microplastics producing significant differences compared to controls. PE and PLA particles inhibited bacterial diversity at low temperatures and promoted bacterial diversity at high temperatures, and TP particles promoted both at both temperatures. For bacterial richness, only PLA showed inhibition at low temperature; all other treatments showed promotion. PE, PLA, and TP microplastics changed the community structure of sediment bacteria, forming two clusters at low and high temperatures. Furthermore, PE, PLA, and TP changed the sediment metabolic profiles, producing differential metabolites such as lipids and molecules, organic heterocyclic compounds, and organic acids and their derivatives, especially TP had the most significant effect. These findings contribute to a more comprehensive understanding of the potential impact of microplastic contamination.IMPORTANCEIn this study, we added 3% (wt/wt) microplastic particles, including polyethylene, polylactic acid, and tire particles, to natural sediments under simulated laboratory conditions. Subsequently, we simulated the sediment microbial and ecosystem responses under different temperature conditions by incubating them for 60 days at 15°C and 35°C, respectively. After synthesizing these results, our study strongly suggests that the presence of microplastics in sediment ecosystems and exposure under different temperature conditions may have profound effects on soil microbial communities, enzyme activities, and metabolite profiles. This is important for understanding the potential hazards of microplastic contamination on terrestrial ecosystems and for developing relevant environmental management strategies.

Temperature-dependent effects of microplastics on sediment bacteriome and metabolome.

The increasing prevalence of microplastics in the environment has become a concern for various ecosystems, including wetland ecosystems. Here, we investigated the effects of three popular microplastic types: polyethylene, polylactic acid, and tire particles at 5 °C and 25 °C on the sediment microbiome and metabolome at the 3% (w/w) level. Results indicated that temperature greatly influenced catalase and neutral phosphatase activities, whereas the type of microplastic had a more significant impact on urease and dehydrogenase activities. The addition of microplastic, especially tire particles, increased microbial diversity and significantly altered the microbial community structure and metabolic profile, leading to the formation of different clusters of microbial communities depending on the temperature. Nonetheless, the effect of temperature on the metabolite composition was less significant. Functional prediction showed that the abundance of functional genes related to metabolism and biogeochemical cycling increased with increasing temperature, especially the tire particles treatment group affected the nitrogen cycling by inhibiting ureolysis and nitrogen fixation. These observations emphasize the need to consider microplastic type and ambient temperature to fully understand the ecological impact of microplastics on microbial ecosystems.

A meta-analytic cognitive framework of nudge and sludge.

Public and private institutions have gained traction in developing interventions to alter people's behaviours in predictable ways without limiting the freedom of choice or significantly changing the incentive structure. A nudge is designed to facilitate actions by minimizing friction, while a sludge is an intervention that inhibits actions by increasing friction, but the underlying cognitive mechanisms behind these interventions remain largely unknown. Here, we develop a novel cognitive framework by organizing these interventions along six cognitive processes: attention, perception, memory, effort, intrinsic motivation and extrinsic motivation. In addition, we conduct a meta-analysis of field experiments (i.e. randomized controlled trials) that contained real behavioural measures (n = 184 papers, k = 184 observations, N = 2 245 373 participants) from 2008 to 2021 to examine the effect size of these interventions targeting each cognitive process. Our findings demonstrate that interventions changing effort are more effective than interventions changing intrinsic motivation, and nudge and sludge interventions had similar effect sizes. However, these results need to be interpreted with caution due to a potential publication bias. This new meta-analytic framework provides cognitive principles for organizing nudge and sludge with corresponding behavioural impacts. The insights gained from this framework help inform the design and development of future interventions based on cognitive insights.

High-Throughput Small Molecule Drug Screening For Age-Related Sleep Disorders Using Drosophila melanogaster.

Sleep, an essential component of health and overall well-being, often presents challenges for older individuals who frequently experience sleep disorders characterized by shortened sleep duration and fragmented patterns. These sleep disruptions also correlate with an increased risk of various illnesses in the elderly, including diabetes, cardiovascular diseases, and psychological disorders. Unfortunately, existing drugs for sleep disorders are associated with significant side effects such as cognitive impairment and addiction. Consequently, the development of new, safer, and more effective sleep disorder medications is urgently needed. However, the high cost and lengthy experimental duration of current drug screening methods remain limiting factors. This protocol describes a cost-effective and high-throughput screening method that utilizes Drosophila melanogaster, a species with a highly conserved sleep regulation mechanism compared to mammals, making it an ideal model for studying sleep disorders in the elderly. By administering various small compounds to aged flies, we can assess their effects on sleep disorders. The sleep behaviors of these flies are recorded using an infrared monitoring device and analyzed with the open-source data package Sleep and Circadian Analysis MATLAB Program 2020 (SCAMP2020). This protocol offers a low-cost, reproducible, and efficient screening approach for sleep regulation. Fruit flies, due to their short life cycle, low husbandry cost, and ease of handling, serve as excellent subjects for this method. As an illustration, Reserpine, one of the tested drugs, demonstrated the ability to promote sleep duration in elderly flies, highlighting the effectiveness of this protocol.

Nudging policymakers on gendered impacts of policy.

Despite the proliferation of nudge research in the last few decades, very little published work aims to nudge the behavior of policymakers. Here we explore the impact of a well-established nudge on policymakers in the Northwest Territories of Canada. In a pre-registered randomized controlled trial, we emailed an invitation to policymakers (N = 263) to attend an online briefing on gendered impacts of policy. In the treatment condition (N = 133), the invitation contained personal stories of two women whose lives were disproportionally impacted by public policies more than men. In the control condition (N = 130), the invitation did not contain such stories. After the briefing, we sent all participants in both conditions a link to a public pledge that they could sign. The pledge was to lead and advocate for equity-oriented policymaking. Contrary to our prediction, there was a small backfiring effect where policymakers in the treatment condition (3.0%) were less likely to attend the briefing than the control condition (7.7%). However, two policymakers (1.5%) in the treatment condition signed the public pledge compared to one (0.8%) in the control condition. The current findings reveal the limits of using personal stories as a nudge to influence policymakers. We discuss insights gained from this experiment and follow-up debriefings with policymakers on how to improve future behavioral interventions designed to nudge policymakers.

Dimensions of beliefs without strong supporting evidence and reasons for holding them.

Beliefs without strong supporting evidence (BWSSE) are commonplace, such as religious beliefs and conspiracy theories. The goals of the current study were to identify dimensions of BWSSE in the general public and study how reasons for holding each dimension depend on the strength of the belief. Participants completed a BWSSE questionnaire online, and principal component analysis suggested that the questionnaire captured 6 dimensions of beliefs that range in strength: New Age Spiritual, Traditional Spiritual, Nonconformist, Science, Mythical, and Conspiracy Theory. Mixed-model analyses of variance showed that while high-strength believers in both New Age and Traditional Spiritual shifted their reasons-for-belief away from 'just believe' and towards personal experience, only Traditional Spiritual shifted away from 'just believe' to culture. In contrast, for Conspiracy Theory and Mythical, the dominant reason for belief was media, but for Conspiracy Theory only, there was a shift from media to education/personal research for high-strength believers. This demonstrates that although spiritual beliefs are strengthened by personal experience, conspiracy theory beliefs are strengthened by information gathering. Understanding the source of an existing belief is important for debiasing attempts to move people towards beliefs with strong supporting evidence, including greater acceptance of evidence provided by experts, a likely requirement for negotiating global humanitarian emergencies in the not-so-distant future. Statement of Relevance. Beliefs without strong supporting evidence (BWSSE) have been gaining attention in mainstream society; particularly, the sources of information that may contribute to their formation and resistance to correction. Understanding the source of an existing belief is important for debiasing attempts to move people towards beliefs with strong supporting evidence, including greater acceptance of evidence provided by experts, a likely requirement for negotiating global humanitarian emergencies in the not-so-distant future.

NG-SEM: an effective non-Gaussian structural equation modeling framework for gene regulatory network inference from single-cell RNA-seq data.

Inference of gene regulatory network (GRN) from gene expression profiles has been a central problem in systems biology and bioinformatics in the past decades. The tremendous emergency of single-cell RNA sequencing (scRNA-seq) data brings new opportunities and challenges for GRN inference: the extensive dropouts and complicated noise structure may also degrade the performance of contemporary gene regulatory models. Thus, there is an urgent need to develop more accurate methods for gene regulatory network inference in single-cell data while considering the noise structure at the same time. In this paper, we extend the traditional structural equation modeling (SEM) framework by considering a flexible noise modeling strategy, namely we use the Gaussian mixtures to approximate the complex stochastic nature of a biological system, since the Gaussian mixture framework can be arguably served as a universal approximation for any continuous distributions. The proposed non-Gaussian SEM framework is called NG-SEM, which can be optimized by iteratively performing Expectation-Maximization algorithm and weighted least-squares method. Moreover, the Akaike Information Criteria is adopted to select the number of components of the Gaussian mixture. To probe the accuracy and stability of our proposed method, we design a comprehensive variate of control experiments to systematically investigate the performance of NG-SEM under various conditions, including simulations and real biological data sets. Results on synthetic data demonstrate that this strategy can improve the performance of traditional Gaussian SEM model and results on real biological data sets verify that NG-SEM outperforms other five state-of-the-art methods.

The change of Siglec-9 expression in peripheral blood NK cells of SFTS patients can affect the function of NK cells.

OBJECTIVES: To investigate the changes and mechanism of Siglec-9 on NK cells in peripheral blood of patients with severe fever with thrombocytopenia syndrome (SFTS). METHODS: First, we used single-cell RNA sequencing to analyze the frequency of NK cells in Peripheral Blood Mononuclear Cells (PBMCs) of SFTS patients and healthy controls (HCs), as well as the differences in the genes on NK cells. Secondly, we analyzed the expression of Siglec-9 and other receptors on NK cells by flow cytometry. Thirdly, we analyzed the correlation between Siglec-9 on NK cells and DBV viral load in plasma. RESULTS: Compared with HCs, the frequency of NK cells in peripheral blood of SFTS patients was significantly decreased, and the activating receptors on NK cells were reduced. The expression of Siglec-9 on NK cells and the frequency of Siglec-9+NK cells decreased significantly in SFTS patients. The expression of Siglec-9 on CD16+CD56dim NK cells was negatively correlated with DBV viral load. In addition, Siglec-9+NK cells expressed higher levels of activating receptors and exhibited stronger effector functions than Siglec-9-NK cells. CONCLUSIONS: The decreased expression of Siglec-9 on NK cells predicts NK cell dysfunction in SFTS patients, suggesting that Siglec-9 may be a potential marker for functional NK cell subsets in SFTS patients.

Immunogenic cell death-based prognostic model for predicting the response to immunotherapy and common therapy in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a malignant tumor in the respiratory system. The efficacy of current treatment modalities varies greatly, and individualization is evident. Therefore, finding biomarkers for predicting treatment prognosis and providing reference and guidance for formulating treatment options is urgent. Cancer immunotherapy has made distinct progress in the past decades and has a significant effect on LUAD. Immunogenic Cell Death (ICD) can reshape the tumor's immune microenvironment, contributing to immunotherapy. Thus, exploring ICD biomarkers to construct a prognostic model might help individualized treatments. We used a lung adenocarcinoma (LUAD) dataset to identify ICD-related differentially expressed genes (DEGs). Then, these DEGs were clustered and divided into subgroups. We also performed variance analysis in different dimensions. Further, we established and validated a prognostic model by LASSO Cox regression analysis. The risk score in this model was used to evaluate prognostic differences by survival analysis. The treatment prognosis of various therapies were also predicted. LUAD samples were divided into two subgroups. The ICD-high subgroup was related to an immune-hot phenotype more sensitive to immunotherapy. The prognostic model was constructed based on six ICD-related DEGs. We found that high-risk score patients responded better to immunotherapy. The ICD prognostic model was validated as a standalone factor to evaluate the ICD subtype of individual LUAD patients, which might contribute to more effective therapies.

3D DNAzyme walker based electrochemical biosensor for attomolar level microRNA-155 detection.

Herein, an ultrasensitive electrochemical biosensor for microRNA-155 (miR-155) detection based on the powerful catalytic and continuous walking signal amplification capability of 3D DNAzyme walker and the gold nanoparticles/graphene aerogels carbon fiber paper-based (AuNPs/GAs/CFP) flexible sensing electrode with excellent electrochemical performance was successfully constructed. In a proof-of-concept experiment, in the presence of miR-155, the DNAzyme strands anchored on the streptavidin-modified magnetic beads (MBs) silenced by locked strands can be activated, thus generating the walking arm of the 3D DNAzyme walker. Meanwhile, the substrate strands modified with Fe-MOF-NH2 nanoparticles were evenly distributed on the surface of MBs and served as tracks of the 3D DNAzyme walker. Once the DNAzyme strand was activated, the catalytic site in the substrate strand can be cleaved in the presence of Mn2+, and a large number of stumps modified with Fe-MOF-NH2 nanoparticles (output@Fe-MOF-NH2) will be generated during the continuous and efficient walking cleavage of the DNAzyme walker, driving the recognition-catalysis-release cycle process for signal amplification. Immediately afterwards, the signal was read out through the base complementary pairing of capture probe (PS) immobilized on the surface of the paper-based flexible sensing electrode AuNPs/GAs/CFP and signal probes output@Fe-MOF-NH2, thus achieving the quantitative detection of miR-155. Under optimal experimental conditions, the designed 3D DNAzyme walker-based biosensor exhibited a relatively lower limit of detection (LOD) of 56.23 aM, with a linear range of 100 aM to 100 nM. Overall, the proposed 3D DNAzyme walker biosensor exhibited good interference and reproducibility, demonstrating a promising future in the field of clinical disease diagnosis.

Identification of immunotherapy biomarkers for improving the clinical outcome of homologous recombination deficiency patients with lung adenocarcinoma.

Homologous recombination deficiency (HRD) is a common molecular signature of genomic instability and has been shown to be a biomarker for targeted therapies. However, there is a lack of studies on the role of HRD changes in lung adenocarcinoma (LUAD) transcriptomics. HRD scores were determined using single nucleotide polymorphism (SNP) array data from LUAD patients from The Cancer Genome Atlas (TCGA) database. Transcriptional data from patients with different scores were analyzed to identify biomarkers associated with HRD. Candidate biomarkers were validated using Gene Expression Omnibus (GEO)-sourced datasets and an immunotherapy cohort. According to the bulk transcriptome and clinical characteristics of 912 LUAD patients and Single-cell RNA-seq of 9 LUAD patients from TCGA and GEO databases, we observed increased MS4A6A expression in HRD tumors; high MS4A6A expression predicted improved survival outcomes. Furthermore, a comprehensive analysis of the tumor immune microenvironment (TIME) revealed a positive correlation between MS4A6A expression and neoantigen loading and immune cell infiltration. Additionally, the immunotherapy cohort confirmed the possibility of using MS4A6A as a biomarker. Collectively, we suggest that MS4A6A is associated with HRD and provide a new perspective toward identifying promising biomarkers for immunotherapy.

i-Frame interventions enhance s-frame interventions.

We argue that i-frame interventions can and do increase support for systemic reforms, and s-frame interventions should be pursued in parallel to address key societal issues. Without accompanying i-frame interventions, s-frame interventions can fail. We offer an operant conditioning framework to generate positive spillover effects. Behavioral scientists should develop i-frame interventions that enhance, rather than compete with, s-frame interventions.

Unconditional cash transfers reduce homelessness.

Homelessness is an economic and social crisis. In a cluster-randomized controlled trial, we address a core cause of homelessness-lack of money-by providing a one-time unconditional cash transfer of CAD$7,500 to each of 50 individuals experiencing homelessness, with another 65 as controls in Vancouver, BC. Exploratory analyses showed that over 1 y, cash recipients spent fewer days homeless, increased savings and spending with no increase in temptation goods spending, and generated societal net savings of $777 per recipient via reduced time in shelters. Additional experiments revealed public mistrust toward the ability of homeless individuals to manage money and demonstrated interventions to increase public support for a cash transfer policy using counter-stereotypical or utilitarian messaging. Together, this research offers a new approach to address homelessness and provides insights into homelessness reduction policies.

Associated Risk Factors and Diagnostic Value of Fiberoptic Bronchoscopy for Protracted Bacterial Bronchitis in Children.

Objective: Untreated protracted bacterial bronchitis (PBB), a chronic wet cough prevalent in children, may lead to chronic suppurative lung disease. However, clinical diagnostic criteria are currently nonspecific; thus, PBB may be misdiagnosed. Thus, we assessed the diagnostic value of fiberoptic bronchoscopy (FOB) and the risk factors associated with PBB. Methods: Children with chronic cough at The First Affiliated Hospital of Anhui Medical University from January 2015 to May 2020 were enrolled and allocated to a suspected PBB (n = 141) or a non-PBB (n = 206) group. All children underwent extensive laboratory, chest imaging, and allergen tests. Children with suspected PBB underwent FOB with bronchoalveolar lavage; lavage and sputum samples were cultured. Results: All 347 children had a chronic wet cough for approximately 2 months. Of 141 children with suspected PBB, 140 received FOB with bronchoalveolar lavage. Visible tracheal changes included pale mucosa, mucosal congestion, edema, swelling, and increased secretions attached to the wall. Sputum was visible primarily in the left main bronchus (78.7%), left lower lobe (59.6%), right upper lobe (62.4%), and right lower lobe (64.5%). Sputum properties and amounts significantly differed between children with vs. without PBB (P < 0.05). Dermatophagoides (odds ratio (OR), 2.642; 95% CI, 1.283-5.369), milk protein (OR, 2.452; 95% CI, 1.243-4.836) allergies, and eczema (OR, 1.763; 95% CI, 1.011-3.075) were risk factors significantly associated with PBB. Conclusion: Dermatophagoides, milk protein, and eczema were associated with an increased risk of PBB. Sputum distribution and tracheal wall changes observed through FOB may distinguish PBB and assist in its diagnosis.