The mechanisms of pH regulation on promoting volatile fatty acids production from kitchen waste.

The anaerobic acid production experiments were conducted with the pretreated kitchen waste under pH adjustment. The results showed that pH 8 was considered to be the most suitable condition for acid production, especially for the formation of acetic acid and propionic acid. The average value of total volatile fatty acid at pH 8 was 8814 mg COD/L, 1.5 times of that under blank condition. The average yield of acetic acid and propionic acid was 3302 mg COD/L and 2891 mg COD/L, respectively. The activities of key functional enzymes such as phosphotransacetylase, acetokinase, oxaloacetate transcarboxylase and succinyl-coA transferase were all enhanced. To further explore the regulatory mechanisms within the system, the distribution of microorganisms at different levels in the fermentation system was obtained by microbial sequencing, results indicating that the relative abundances of Clostridiales, Bacteroidales, Chloroflexi, Clostridium, Bacteroidetes and Propionibacteriales, which were great contributors for the hydrolysis and acidification, increased rapidly at pH 8 compared with the blank group. Besides, the proportion of genes encoding key enzymes was generally increased, which further verified the mechanism of hydrolytic acidification and acetic acid production of organic matter under pH regulation.

Mindfulness trait and the potential mediating role of emotional regulation strategies in bipolar disorder / Mindfulness rasgo y el potencial papel mediador de las estrategias de regulación emocional en el trastorno bipolar

En este estudio transversal se investiga la asociación entre los principales síntomas del Trastorno bipolar (TB) y las dificultades asociadas a las estrategias de regulación emocional (ERE) adaptativas y desadaptativas. Además, este estudio examina los efectos mediadores de las ERE con el mindfulness rasgo y el TB. Método. Veinticuatro adultos con TB completaron la Escala de Conciencia de Atención Plena (MAAS), el Inventario de Depresión de Beck (BDI-II), la Escala de Autoevaluación de Manía de Altman (ARSM), el Inventario de Ansiedad Rasgo (STAI-R), y el Cuestionario de Regulación Emocional Cognitiva (CERQ). Resultados. El análisis de regresión múltiple mostró cómo la depresión se relacionaba significativa y positivamente con la autoculpabilización, mientras que la ansiedad rasgo estaba positivamente asociada con la autoculpabilización y el catastrofismo. En segundo lugar, el análisis de mediación mostró un efecto de mediación significativo para la autoculpabilidad en la relación entre mindfulness y depresión (a*b = -.15; ICB 95% [-.36, -.03]) y entre mindfulness y ansiedad rasgo (a*b = -.09; ICB 95% [-.27, -.01]). Conclusiones. Nuestros resultados informan del papel de la auto-culpabilidad y el catastrofismo en el TB y de cómo éstas podrían mediar significativamente entre el mindfulness rasgo y el TB. Estos resultados sugieren que una práctica de meditación enfocada en el catastrofismo y la autoculpabilidad puede ser especialmente útil para reducir los síntomas en los pacientes bipolares.(AU)

This cross-sectional study investigates the association between the main symptoms of Bipolar disorder (BD) and emotional regulation dif-ficulties in adaptive and maladaptive emotional regulation strategies (ERS). In addition, this study examines the possible mediating effects of ERS with dispositional mindfulnessand bipolar symptoms. Method.Twenty-four adults diagnosed with BD completed the Mindful Attention Awareness Scale (MAAS), the Beck Depression Inventory (BDI-II), the Altman Mania Self-Assessment Scale (ARSM), the Trait Anxiety Inventory (STAI-R), and the Cognitive Emotional Regulation Questionnaire (CERQ). Results. First, mul-tiple regression analysis showed how depression was significantly positively related to self-blame, whereas trait anxietywas positively associated with self-blame and catastrophizing. Second, the results of the mediation analy-sis have shown a significant mediation effect for the self-blamein the rela-tionship between mindfulnessand depression (a*b = -.15; BCI 95% [-.36, -.03]) and between mindfulnessand trait anxiety (a*b = -.09; BCI 95% [-.27, -.01]). Conclusions. Our results report the role of self-blame and catastrophiz-ing in BD and how these might significantly mediate between dispositional mindfulness and symptoms of depression and anxiety. These results suggest that a meditation practice focused on reducing catastrophizing and self-blame may be especially helpful for symptoms of depression and anxiety in bipolar patients.(AU)

Anxiety and curiosity in hierarchical models of neural emotion processing-A mini review.

Traditionally, two fundamentally different theoretical approaches have been used in emotion research to model (human) emotions: discrete emotion theories and dimensional approaches. More recent neurophysiological models like the hierarchical emotion theory suggest that both should be integrated. The aim of this review is to provide neurocognitive evidence for this perspective with a particular focus on experimental studies manipulating anxiety and/or curiosity. We searched for evidence that the neuronal correlates of discrete and dimensional emotional systems are tightly connected. Our review suggests that the ACC (anterior cingulate cortex) responds to both, anxiety, and curiosity. While amygdala activation has been primarily observed for anxiety, at least the NAcc (nucleus accumbens) responds to both, anxiety and curiosity. When these two areas closely collaborate, as indicated by strong connectivity, this may indicate emotion regulation, particularly when the situation is not predictable.

Regulation of emotions in project-based collaborative learning: an empirical study in academic English classrooms.

In spite of the increasing popularity of project-based collaborative learning (PBCL) as a pedagogy, real successful collaboration cannot always be achieved due to the cognitive, motivational and social emotional challenges students encounter during collaboration. Recognizing the challenges and developing regulation strategies to cope with the challenges at both individual and group level is essential for successful collaboration. In the last decades, a growing interest has been developed around socially shared regulation of emotions and how it is interwoven with self-regulation and co-regulation. However, capturing the process of students' emotional challenges and regulations in a long and dynamic project proves difficult and there remains a paucity of evidence on how co-regulation and socially-shared regulation co-occur with learners' cognitive and emotional progress in project-based collaborative learning. The purpose of the present study is to investigate and identify what kind of social emotional challenges students encountered during PBCL and how they regulate themselves and the groups in order to finish the projects. A quasi-experimental research design was adopted in an academic English classroom, with thirty-eight students self-reporting their challenges and regulations three times after finishing each of the projects. The results of qualitative analysis plus a case study of two groups indicate that students encounter a variety of social emotional challenges and employed different levels of co-regulation and socially shared regulation in addition to self-regulation, leading to varying collaboration results and experiences. The findings of the study offer insights into the emotional regulation in PBCL and shed light for future design of pedagogical interventions aiming at supporting socially shared regulation.

Reverse social contagion as a mechanism for regulating mass behaviors in highly integrated social systems.

Mass behavior is the rapid adoption of similar conduct by all group members, with potentially catastrophic outcomes such as mass panic. Yet, these negative consequences are rare in integrated social systems such as social insect colonies, thanks to mechanisms of social regulation. Here, we test the hypothesis that behavioral deactivation between active individuals is a powerful social regulator that reduces energetic spending in groups. Borrowing from scaling theories for human settlements and using behavioral data on harvester ants, we derive ties between the hypermetric scaling of the interaction network and the hypometric scaling of activity levels, both relative to the colony size. We use elements of economics theory and metabolic measurements collected with the behavioral data to link activity and metabolic scalings with group size. Our results support the idea that metabolic scaling across social systems is the product of different balances between their social regulation mechanisms.

Widespread changes to the translational landscape in a maize microRNA biogenesis mutant.

MicroRNAs are short, non-coding RNAs that repress gene expression in both plants and animals and have diverse functions related to growth, development, and stress responses. The ribonuclease, DICER-LIKE1 (DCL1) is required for two steps in plant miRNA biogenesis: cleavage of the primary miRNAs (pri-miRNAs) to release a hairpin structure, called the precursor miRNA (pre-miRNA) and cleavage of the pre-miRNA to generate the miRNA/miRNA* duplex. The mature miRNA guides the RNA-induced silencing complex to target RNAs with complementary sequences, resulting in translational repression and/or RNA cleavage of target mRNAs. However, the relative contribution of translational repression versus mRNA degradation by miRNAs remains unknown at the genome-level in crops, especially in maize. The maize fuzzy tassel (fzt) mutant contains a hypomorphic mutation in DCL1 resulting in broad developmental defects. While most miRNAs are reduced in fzt, the levels of miRNA-targeted mRNAs are not dramatically increased, suggesting that translational regulation by miRNAs may be common. To gain insight into the repression mechanism of plant miRNAs, we combined ribosome profiling and RNA-sequencing to globally survey miRNA activities in maize. Our data indicate that translational repression contributes significantly to regulation of most miRNA targets and that approximately one-third of miRNA targets are regulated primarily at the translational level. Surprisingly, ribosomes appear altered in fzt mutants suggesting that DCL1 may also have a role in ribosome biogenesis. Thus, DICER-LIKE1 shapes the translational landscape in plants through both miRNA-dependent and miRNA-independent mechanisms.

Germline-specific RNA helicase DDX4 forms cytoplasmic granules in cancer cells and promotes tumor growth.

Cancer cells undergo major epigenetic alterations and transcriptomic changes, including ectopic expression of tissue- and cell-type-specific genes. Here, we show that the germline-specific RNA helicase DDX4 forms germ-granule-like cytoplasmic ribonucleoprotein granules in various human tumors, but not in cultured cancer cells. These cancerous DDX4 complexes contain RNA-binding proteins and splicing regulators, including many known germ granule components. The deletion of DDX4 in cancer cells induces transcriptomic changes and affects the alternative splicing landscape of a number of genes involved in cancer growth and invasiveness, leading to compromised capability of DDX4-null cancer cells to form xenograft tumors in immunocompromised mice. Importantly, the occurrence of DDX4 granules is associated with poor survival in patients with head and neck squamous cell carcinoma and higher histological grade of prostate cancer. Taken together, these results show that the germ-granule-resembling cancerous DDX4 granules control gene expression and promote malignant and invasive properties of cancer cells.

The stromal side of the cytochrome b6f complex regulates state transitions.

In oxygenic photosynthesis, state transitions distribute light energy between Photosystem I and Photosystem II. This regulation involves reduction of the plastoquinone pool, activation of the State Transitions 7 (STT7) protein kinase by the cytochrome b6f complex, and phosphorylation and migration of Light Harvesting Complex II (LHCII). Here, we show that in Chlamydomonas reinhardtii, the C-terminus of the cyt b6 subunit PetB acts on phosphorylation of STT7 and state transitions. We used site-directed mutagenesis of the chloroplast petB gene to truncate (remove L215b6) or elongate (add G216b6) the cyt b6 subunit. Modified complexes are devoid of heme ci and degraded by FTSH protease, revealing that salt bridge formation between cyt b6 (PetB) and subunit IV (PetD) is key to the assembly of the complex. In double mutants where FTSH is inactivated, modified cyt b6f accumulated but the phosphorylation cascade was blocked. We also replaced the arginine interacting with heme ci propionate (R207Kb6). In this modified complex, heme ci is present but the kinetics of phosphorylation are slower. We show that highly phosphorylated forms of STT7 accumulated transiently after reduction of the PQ pool and represent the active forms of the protein kinase. Phosphorylation of the LHCII targets is favored at the expense of the protein kinase, and the migration of LHCII towards PSI is the limiting step for state transitions.

Organic Cations Texture Zinc Metal Anodes for Deep Cycling Aqueous Zinc Batteries.

Manipulating the crystallographic orientation of zinc (Zn) metal to expose more (002) planes is promising to stabilize Zn anodes in aqueous electrolytes. However, there remain challenges involving the non-epitaxial electrodeposition of highly (002) textured Zn metal and the maintenance of (002) texture under deep cycling conditions. Herein, a novel organic imidazolium cations-assisted non-epitaxial electrodeposition strategy to texture electrodeposited Zn metals is developed. Taking the 1-butyl-3-methylimidazolium cation (Bmim+) as a paradigm additive, the as-prepared Zn film ((002)-Zn) manifests a compact structure and a highly (002) texture without containing (100) signal. Mechanistic studies reveal that Bmim+ featuring oriented adsorption on the Zn-(002) plane can reduce the growth rate of (002) plane to render the final exposure of (002) texture, and homogenize Zn nucleation and suppress H2 evolution to enable the compact electrodeposition. In addition, the formulated Bmim+-containing ZnSO4 electrolyte effectively sustains the (002) texture even under deep cycling conditions. Consequently, the combination of (002) texture and Bmim+-containing electrolyte endows the (002)-Zn electrode with superior cycling stability over 350 h under 20 mAh cm-2 with 72.6% depth-of-discharge, and assures the stable operation of full Zn batteries with both coin-type and pouch-type configurations, significantly outperforming the (002)-Zn and commercial Zn-based batteries in Bmim+-free electrolytes.

Threat, Emotion Dysregulation, and Parenting in a Clinical Sample of Children with Disruptive Behaviour.

Early-life adversity is associated with the development of internalizing and externalizing problems in children. Despite this, there is a need to understand the mechanisms linking these experiences to psychopathology, especially in clinical samples. This cross-sectional study tested emotion dysregulation as a mechanism linking early-life threat to psychopathology in a clinical sample of children with disruptive behavior problems. We also explored parental positive reinforcement as a protective factor in these pathways. A clinical sample of 606 children aged 6-12 years, referred to a mental healthcare hospital, were included. Parent-reported child threat, and parent- and teacher-reported child emotion dysregulation and psychopathology, were collected. Path analysis was used to explore the mediating effect of emotion dysregulation in the relation between threat and psychopathology. The moderating effects of parental positive reinforcement were explored through moderated-mediation analyses. Emotion dysregulation partially mediated the association between threat and both internalizing (ß = .18, P = .006) and externalizing (ß = .19, P = .002) problems. Positive reinforcement did not buffer the association between threat and emotion dysregulation (ß = .09, P = .62) or the association between emotion dysregulation and internalizing (ß = - .003, P = .20) or externalizing (ß = - .002, P = .35). Poor emotion regulation may be a transdiagnostic mechanism linking early-threat with internalizing and externalizing problems in clinic-referred children with disruptive behaviors. Factors aside from parental positive reinforcement should be explored as protective factors in these pathways, including those directly implicated in the purported mechanisms linking these factors over time.

The Expression of Non B Cell-Derived Immunoglobulins.

Although V(D)J recombination and immunoglobulin (Ig) production are traditionally recognised to occur only in B lymphocytes and plasma cells, the expression of Igs in non-lymphoid cells, which we call non B cell-derived Igs (non B Igs), has been documented by growing studies. It has been demonstrated that non B-Igs can be widely expressed in most cell types, including, but not limited to, epithelial cells, cardiomyocytes, hematopoietic stem/progenitor cells, myeloid cells, and cells from immune-privileged sites, such as neurons and spermatogenic cells. In particular, malignant tumour cells express high level of IgG. Moreover, different from B-Igs that mainly localised on the B cell membrane and in the serum and perform immune defence function mainly, non B-Igs have been found to distribute more widely and play critical roles in immune defence, maintaining cell proliferation and survival, and promoting progression. The findings of non B-Igs may provide a wealthier breakthrough point for more therapeutic strategies for a wide range of immune-related diseases.

Targeting RNA N6-methyladenosine modification-- a novel therapeutic target for HER2- positive gastric cancer.

Gastric cancer is one of the most common cancers and is considered the 5th most frequent occurring cancer worldwide. It has gained great attention from the clinicians and researchers because of high mortality rate. It is generally treated with chemotherapy, radiotherapy, and surgery. Recently, additional treatment options including immunotherapy and targeted therapy and immunotherapy have been developed. However, poor prognosis, limited survival rate of patients, and drug resistance to treatment remain critical problems. To improve treatment options or to overcome the bottleneck of treatment, identification of diagnostic and prognostic markers, determining the most effective therapeutic options, and uncovering the molecular regulations associated with treatment strategies are required. In this regard n6-methyladenosine (m6A) regulation is considered important. This reversible modification plays a crucial role in progression, development and treatment of HER2-positive gastric cancer. Here, we discuss the role of m6A modification in HER2-positive gastric cancer progression through collecting related studies at present. We further discuss the association of m6A modification with therapeutic efficacy in HER2-positive gastric cancer and list some examples. We conclude that modification of m6A can be a new strategy for improving the prognosis and survival rate of HER2-positive gastric cancer patients.

Exercise therapy in the application of sleep disorders.

Sleep disorders often accompany neurological injuries, significantly impacting patient recovery and quality of life.The efficacy and adherence of traditional treatment methods have certain limitations. Exercise has been found to be a highly beneficial treatment method, capable of preventing and alleviating neurological injuries and sleep disorders. This article reviews relevant research findings from both domestic and international sources over the past few decades, systematically summarizing and analyzing the application of exercise therapy in sleep disorders,strategy of exercise intervention program and the potential molecular mechanisms by which exercise therapy improves sleep disorders. Shortcomings in current research and suggestions are presented, providing a reference for future in-depth studies on exercise interventions for sleep disorders.

Pro-survival signaling regulates lipophagy essential for multiple myeloma resistance to stress-induced death.

Pro-survival metabolic adaptations to stress in tumorigenesis remain less well defined. We find that multiple myeloma (MM) is unexpectedly dependent on beta-oxidation of long-chain fatty acids (FAs) for survival under both basal and stress conditions. However, under stress conditions, a second pro-survival signal is required to sustain FA oxidation (FAO). We previously found that CD28 is expressed on MM cells and transduces a significant pro-survival/chemotherapy resistance signal. We now find that CD28 signaling regulates autophagy/lipophagy that involves activation of the Ca2+→AMPK→ULK1 axis and regulates the translation of ATG5 through HuR, resulting in sustained lipophagy, increased FAO, and enhanced MM survival. Conversely, blocking autophagy/lipophagy sensitizes MM to chemotherapy in vivo. Our findings link a pro-survival signal to FA availability needed to sustain the FAO required for cancer cell survival under stress conditions and identify lipophagy as a therapeutic target to overcome treatment resistance in MM.

A tandem activity-based sensing and labeling strategy reveals antioxidant response element regulation of labile iron pools.

Iron is an essential element for life owing to its ability to participate in a diverse array of oxidation-reduction reactions. However, misregulation of iron-dependent redox cycling can also produce oxidative stress, contributing to cell growth, proliferation, and death pathways underlying aging, cancer, neurodegeneration, and metabolic diseases. Fluorescent probes that selectively monitor loosely bound Fe(II) ions, termed the labile iron pool, are potentially powerful tools for studies of this metal nutrient; however, the dynamic spatiotemporal nature and potent fluorescence quenching capacity of these bioavailable metal stores pose challenges for their detection. Here, we report a tandem activity-based sensing and labeling strategy that enables imaging of labile iron pools in live cells through enhancement in cellular retention. Iron green-1 fluoromethyl (IG1-FM) reacts selectively with Fe(II) using an endoperoxide trigger to release a quinone methide dye for subsequent attachment to proximal biological nucleophiles, providing a permanent fluorescent stain at sites of elevated labile iron. IG1-FM imaging reveals that degradation of the major iron storage protein ferritin through ferritinophagy expands the labile iron pool, while activation of nuclear factor-erythroid 2-related factor 2 (NRF2) antioxidant response elements (AREs) depletes it. We further show that lung cancer cells with heightened NRF2 activation, and thus lower basal labile iron, have reduced viability when treated with an iron chelator. By connecting labile iron pools and NRF2-ARE activity to a druggable metal-dependent vulnerability in cancer, this work provides a starting point for broader investigations into the roles of transition metal and antioxidant signaling pathways in health and disease.

Investigating and Engineering an 1,2-Propanediol-Responsive Transcription Factor-Based Biosensor.

Transcription factor (TF)-based biosensors have arisen as powerful tools in the advancement of metabolic engineering. However, with the emergence of numerous bioproduction targets, the variety of applicable TF-based biosensors remains severely limited. In this study, we investigated and engineered an 1,2-propanediol (1,2-PD)-responsive transcription activator, PocR, from Salmonella typhimurium to enrich the current biosensor repertoire. Heterologous characterization of PocR in E. coli revealed a significantly limited operational range and dynamic range, primarily attributed to the leaky binding between PocR and its corresponding promoters in the absence of the 1,2-PD inducer. Promiscuity characterization uncovered the minor responsiveness of PocR toward glycerol and 1,2-butanediol (1,2-BD). Using AlphaFold-predicted structure and protein mutagenesis, we preliminarily explored the underlying mechanism of PocR. Based on the investigated mechanism, we engineered a PcoR-F46R/G105D variant with an altered inducer specificity to glycerol, as well as a PocR-ARE (Q107A/S192R/A203E) variant with nearly a 4-fold higher dynamic range (6.7-fold activation) and a 20-fold wider operational range (0-20 mM 1,2-PD). Finally, we successfully converted PocR to a repressor through promoter engineering. Integrating the activation and repression functions established a versatile 1,2-PD-induced bifunctional regulation system based on PocR-ARE. Our work showcases the exploration and exploitation of an underexplored type of transcriptional activator capable of recruiting RNA polymerase. It also expands the biosensor toolbox by providing a 1,2-PD-responsive bifunctional regulator and glycerol-responsive activator.

How should regulatory schemes be optimized to enhance deterrence against medical insurance fraud by enrollees? Evidence from a discrete choice experiment in China.

Medical insurance fraud (MIF) poses a substantial global financial challenge, necessitating effective regulatory strategies, especially in China, where such measures are in a critical developmental phase. This study investigates the effectiveness of various regulatory components in deterring MIF among enrollees and explores preference heterogeneity among individuals with different characteristics, utilizing a discrete choice experiment survey. Grounded in deterrence theory, our conceptual framework incorporates five attributes: intensity of economic penalties, restrictions on medical insurance benefits, deterioration of social reputation, and certainty and celerity of penalties. Employing a D-efficiency design, 24 choice sets were generated and blocked into three versions. A multistage stratified sampling method was adopted to collect data from the basic medical insurance enrollees in Shanghai. The survey was conducted from September to October 2022. The sample representativeness was further improved via the entropy balancing approach. Data from the final sample of 1034 respondents were analyzed using mixed logit models (MIXLs), incorporating interactions with individual characteristics to assess preference heterogeneity. Results reveal that escalating economic penalties, suspending insurance benefits, listing individuals as unfaithful parties, ensuring penalty certainty, and expediting enforcement significantly enhance the deterrent effect. We observed preference heterogeneity across different demographics, including age, gender, education, health status, and employment status. The study underscores the pivotal role of economic penalties in deterring MIF, while also acknowledging the significance of non-economic measures such as enforcement efficiency and social sanctions. These findings offer valuable insights for policymakers to tailor and strengthen regulatory schemes against MIF, contributing to the advancement of more effective and precise healthcare policies.

Elucidating regulation of polyhydroxyalkanoate metabolism in R. eutropha: Identification of transcriptional regulators from phasin and depolymerase genes.

Despite the ever-growing research interest in polyhydroxyalkanoates (PHAs) as green plastic alternatives, our understanding of the regulatory mechanisms governing PHA synthesis, storage, and degradation in the model organism Ralstonia eutropha remains limited. Given its importance for central carbon metabolism, PHA homeostasis is probably controlled by a complex network of transcriptional regulators. Understanding this fine-tuning is key for developing improved PHA production strains thereby boosting the application of PHAs. We conducted promoter pull-down assays with crude protein extracts from R. eutropha Re2058/pCB113, followed by LC-MS/MS, to identify putative transcriptional regulators involved in the expression control of PHA metabolism, specifically targeting phasin phaP1 and depolymerase phaZ3 and phaZ5 genes. The impact on promoter activity was studied in vivo using ß-galactosidase assays and the most promising candidates were heterologously produced in Escherichia coli and their interaction with the promoters investigated in vitro by Electrophoretic Mobility Shift Assays. We could show that R. eutropha DNA-binding XRE-family-like protein H16_B1672, specifically binds the phaP1 promoter in vitro with a KD of 175 nM and represses gene expression from this promoter in vivo. Protein H16_B1672 also showed interaction with both depolymerase promoters in vivo and in vitro suggesting a broader role in the regulation of PHA metabolism. Furthermore, in vivo assays revealed that the H-NS-like DNA-binding protein H16_B0227 and the peptidyl-prolyl cis-trans isomerase PpiB, strongly repress gene expression from PphaP1 and PphaZ3, respectively. In summary, this study provides new insights into the regulation of PHA metabolism in R. eutropha, uncovering specific interactions of novel transcriptional regulators.

Distinct regions of its first intracellular loop contribute to the proper localization, transport activity and substrate-affinity adjustment of the main yeast K+ importer Trk1.

Trk1 is the main K+ importer of Saccharomyces cerevisiae. Its proper functioning enables yeast cells to grow in environments with micromolar amounts of K+. Although the structure of Trk1 has not been experimentally determined, the transporter is predicted to be composed of four MPM (transmembrane segment - pore loop - transmembrane segment) motifs which are connected by intracellular loops. Of those, in particular the first loop (IL1) is unique in its length; it forms more than half of the entire protein. The deletion of the majority of IL1 does not abolish the transport activity of Trk1. However IL1 is thought to be involved in the modulation of the transporter's functioning. In this work, we prepared a series of internally shortened versions of Trk1 that lacked various parts of IL1, and we studied their properties in S. cerevisiae cells without chromosomal copies of TRK genes. Using this approach, we were able to determine that both N- and C-border regions of IL1 are necessary for the proper localization of Trk1. Moreover, the N-border part of IL1 is also important for the functioning of Trk1, as its absence resulted in a decrease in the transporter's substrate affinity. In addition, in the internal part of IL1, we newly identified a stretch of amino-acid residues that are indispensable for retaining the transporter's maximum velocity, and another region whose deletion affected the ability of Trk1 to adjust its affinity in response to external levels of K+.

Urgent action needed: addressing the regulatory gap in e-cigarette trade and usage.

Tobacco use is associated with serious health problems. Global efforts, such as the World Health Organization's Framework for Tobacco Control, have reduced tobacco use, but challenges remain. Initially perceived as aids for smoking cessation, e-cigarettes have gained popularity among young people and non-smokers. Government approaches to regulating e-cigarettes range from treating them like tobacco, requiring a prescription for their use to outright bans. Although touted as a valuable alternative, evidence suggests that increased e-cigarette use carries potential direct and indirect health risks, necessitating urgent regulatory measures on a global scale. Lack of defined and uniform regulations poses substantial public health risks, compounded by marketing targeting vulnerable groups. Immediate interventions, public awareness, and research are essential to effectively control the current e-cigarette epidemic.