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Probiotics are live microorganisms that offer potential benefits to their hosts and can occasionally influence behavioral responses. However, the detailed mechanisms by which probiotics affect the behavior of their hosts and the underlying biogenic effects remain unclear. Lactic acid bacteria, specifically Lactobacillus spp. are known probiotics. Drosophila melanogaster, commonly known as the fruit fly, is a well-established model organism for investigating the interaction between the host and gut microbiota in translational research. Herein, we showed that 5-day administration of Lactobacillus acidophilus (termed GMNL-185) or Lacticaseibacillus rhamnosus (termed GMNL-680) enhances olfactory-associative memory in Drosophila. Moreover, a combined diet of GMNL-185 and GMNL-680 demonstrated synergistic effects on memory functions. Live brain imaging revealed a significant increase in calcium responses to the training odor in the mushroom body β and γ lobes of flies that underwent mixed feeding with GMNL-185 and GMNL-680. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and whole-mount brain immunohistochemistry revealed significant upregulation of lactate dehydrogenase (LDH) expression in the fly brain following the mixed feeding. Notably, the genetic knockdown of Ldh in neurons, specifically in mushroom body, ameliorated the beneficial effects of mixed feeding with GMNL-185 and GMNL-680 on memory improvement. Altogether, our results demonstrate that supplementation with L. acidophilus and L. rhamnosus enhances memory functions in flies by increasing brain LDH levels.

Thermosensation is critical for the survival of animals. However, mechanisms through which nutritional status modulates thermosensation remain unclear. Herein, we showed that hungry Drosophila exhibit a strong hot avoidance behavior (HAB) compared to food-sated flies. We identified that hot stimulus increases the activity of α'β' mushroom body neurons (MBns), with weak activity in the sated state and strong activity in the hungry state. Furthermore, we showed that α'β' MBn receives the same level of hot input from the mALT projection neurons via cholinergic transmission in sated and hungry states. Differences in α'β' MBn activity between food-sated and hungry flies following heat stimuli are regulated by distinct Drosophila insulin-like peptides (Dilps). Dilp2 is secreted by insulin-producing cells (IPCs) and regulates HAB during satiety, whereas Dilp6 is secreted by the fat body and regulates HAB during the hungry state. We observed that Dilp2 induces PI3K/AKT signaling, whereas Dilp6 induces Ras/ERK signaling in α'β' MBn to regulate HAB in different feeding conditions. Finally, we showed that the 2 α'β'-related MB output neurons (MBONs), MBON-α'3 and MBON-β'1, are necessary for the output of integrated hot avoidance information from α'β' MBn. Our results demonstrate the presence of dual insulin modulation pathways in α'β' MBn, which are important for suitable behavioral responses in Drosophila during thermoregulation under different feeding states.

Temperature has a significant effect on all physiological processes of animals. Suitable temperatures promote responsiveness, movement, metabolism, growth, and reproduction in animals, whereas extreme temperatures can cause injury or even death. Thus, thermosensation is important for survival in all animals. However, mechanisms regulating thermosensation remain unexplored, mostly because of the complexity of mammalian neural circuits. The fruit fly Drosophila melanogaster achieves a desirable body temperature through ambient temperature fluctuations, sunlight exposure, and behavioral strategies. The availability of extensive genetic tools and resources for studying Drosophila have enabled scientists to unravel the mechanisms underlying their temperature preference. Over the past 20 years, Drosophila has become an ideal model for studying temperature-related genes and circuits. This review provides a comprehensive overview of our current understanding of thermosensation and temperature preference in Drosophila. It encompasses various aspects, such as the mechanisms by which flies sense temperature, the effects of internal and external factors on temperature preference, and the adaptive strategies employed by flies in extreme-temperature environments. Understanding the regulating mechanisms of thermosensation and temperature preference in Drosophila can provide fundamental insights into the underlying molecular and neural mechanisms that control body temperature and temperature-related behavioral changes in other animals.

Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcers, and gastric cancer. Infection of cells with H. pylori is dependent on lipid rafts, which are cholesterol-rich microdomains located in the cell membrane. H. pylori cholesterol-α-glucosyltransferase (CGT) catalyzes the conversion of membrane cholesterol to cholesteryl glucosides, which can be incorporated into the bacterial cell wall, facilitating evasion from immune defense and colonization in the host. However, the detailed mechanisms underlying this process remain to be explored. In this study, we discovered for the first time that H. pylori CGT could promote adherence to gastric epithelial cells in a cholesterol-dependent manner. Externalization of cell membrane phosphatidylserine (PS) is crucial for enhancement of binding of H. pylori to cells by CGT and for cytotoxin-associated gene A (CagA)-induced pathogenesis. Furthermore, exogenous cholesterol interferes with the actions of H. pylori CGT to catalyze cellular cholesterol, which impedes bacterial binding to cells and attenuates subsequent inflammation, indicating that the initial attachment of H. pylori to cells is closely dependent on host cholesterol. These results provide evidence that CGT contributes to H. pylori infectivity and it may serve as a key target for the treatment of H. pylori-associated diseases.

Background/purpose: Although laparoscopic liver resection (LLR) is a common surgical procedure for hepatocellular carcinoma (HCC), its suitability for large HCCs (≥5 cm) remains controversial. This study compared surgical outcomes of open hepatectomy with LLR for large HCCs. Methods: A total of 313 patients with HCC who underwent hepatectomy between January 2010 and June 2017 were analyzed retrospectively. Demographic data, short-term outcomes, and long-term survivals were analyzed. Results: Among patients with large HCCs (n = 122), the open group (n = 85) had larger tumor sizes (10.91 ± 4.72 vs. 7.45 ± 2.95 cm; p

We have prepared graphene quantum dots (GQDs) and boron-doped GQDs (BGQDs) utilizing spent coffee grounds (SCGs) via a simple one-step hydrothermal process for glucose sensor application. FTIR and XPS characterizations reveal that the boron atoms have been successfully doped into graphene structures. BGQDs on glassy carbon electrode (GCE) in PBS were found to be two times as active compared to GCE/GQDs electrodes. The significant difference in electrochemical activity shown by BGQDs is evidence that boron from boric acid was doped into the graphene dominion. The generation of boronic acid groups on the boron-doped graphene quantum dots (BGQDs) surfaces facilitates the application of GQDs as a new photoluminescence (PL) probe for label-free glucose sensing. The photoluminescence of developed GQDs showed a linear response to glucose over a concentration range of 5–45 mM with a limit of detection of 12.45 mM whereas BGQDs biosensor was found to exhibit a higher sensitivity over the same concentration range with limit of detection of 3.23 mM towards glucose sensing. These results demonstrate that the synthesized BGQD has a promising potential in electrochemical activity and efficient to the PL enhancement mechanism determination of glucose.

Memory consolidation is a time-dependent process through which an unstable learned experience is transformed into a stable long-term memory; however, the circuit and molecular mechanisms underlying this process are poorly understood. The Drosophila mushroom body (MB) is a huge brain neuropil that plays a crucial role in olfactory memory. The MB neurons can be generally classified into three subsets: γ, αβ, and α′β′. Here, we report that water-reward long-term memory (wLTM) consolidation requires activity from α′β′-related mushroom body output neurons (MBONs) in a specific time window. wLTM consolidation requires neurotransmission in MBON-γ3β′1 during the 0–2 h period after training, and neurotransmission in MBON-α′2 is required during the 2–4 h period after training. Moreover, neurotransmission in MBON-α′1α′3 is required during the 0–4 h period after training. Intriguingly, blocking neurotransmission during consolidation or inhibiting serotonin biosynthesis in serotoninergic dorsal paired medial (DPM) neurons also disrupted the wLTM, suggesting that wLTM consolidation requires serotonin signals from DPM neurons. The GFP Reconstitution Across Synaptic Partners (GRASP) data showed the connectivity between DPM neurons and MBON-γ3β′1, MBON-α′2, and MBON-α′1α′3, and RNAi-mediated silencing of serotonin receptors in MBON-γ3β′1, MBON-α′2, or MBON-α′1α′3 disrupted wLTM. Taken together, our results suggest that serotonin released from DPM neurons modulates neuronal activity in MBON-γ3β′1, MBON-α′2, and MBON-α′1α′3 at specific time windows, which is critical for the consolidation of wLTM in Drosophila.

Long-term memory (LTM) formation depends on the conversed cAMP response element-binding protein (CREB)-dependent gene transcription followed by de novo protein synthesis. Thirsty fruit flies can be trained to associate an odor with water reward to form water-reward LTM (wLTM), which can last for over 24 hours without a significant decline. The role of de novo protein synthesis and CREB-regulated gene expression changes in neural circuits that contribute to wLTM remains unclear. Here, we show that acute inhibition of protein synthesis in the mushroom body (MB) αβ or γ neurons during memory formation using a cold-sensitive ribosome-inactivating toxin disrupts wLTM. Furthermore, adult stage-specific expression of dCREB2b in αβ or γ neurons also disrupts wLTM. The MB αβ and γ neurons can be further classified into five different neuronal subsets including αβ core, αβ surface, αβ posterior, γ main, and γ dorsal. We observed that the neurotransmission from αβ surface and γ dorsal neuron subsets is required for wLTM retrieval, whereas the αβ core, αβ posterior, and γ main are dispensable. Adult stage-specific expression of dCREB2b in αβ surface and γ dorsal neurons inhibits wLTM formation. In vivo calcium imaging revealed that αβ surface and γ dorsal neurons form wLTM traces with different dynamic properties, and these memory traces are abolished by dCREB2b expression. Our results suggest that a small population of neurons within the MB circuits support long-term storage of water-reward memory in Drosophila.

Mounting evidence indicates that the gut microbiota is linked to several physiological processes and disease development in mammals; however, the underlying mechanisms remained unexplored mostly due to the complexity of the mammalian gut microbiome. The fruit fly, Drosophila melanogaster, is a valuable animal model for studying host-gut microbiota interactions in translational aspects. The availability of powerful genetic tools and resources in Drosophila allowed the scientists to unravel the mechanisms by which the gut microbes affect fitness, health, and behavior of their hosts. Drosophila models have been extensively used not only to study animal behaviors (i.e., courtship, aggression, sleep, and learning & memory), but also some human related neurodegenerative diseases (i.e., Alzheimer’s disease and Parkinson’s disease) in the past. This review comprehensively summarizes the current understanding of the gut microbiota of Drosophila and its impact on fly behavior, physiology, and neurodegenerative diseases.

Distinct subsets of dopaminergic PAM neurons have been shown to be involved in short-term and long-term memory for sugar reward. Here the authors report the neural circuits and the cellular and molecular mechanisms for short-term and long-term memory for water reward in thirstyDrosophila.

Electrical synapses between neurons, also known as gap junctions, are direct cell membrane channels between adjacent neurons. Gap junctions play a role in the synchronization of neuronal network activity; however, their involvement in cognition has not been well characterized. Three-hour olfactory associative memory in Drosophila has two components: consolidated anesthesia-resistant memory (ARM) and labile anesthesia-sensitive memory (ASM). Here, we show that knockdown of the gap junction gene innexin5 (inx5) in mushroom body (MB) neurons disrupted ARM, while leaving ASM intact. Whole-mount brain immunohistochemistry indicated that INX5 protein was preferentially expressed in the somas, calyxes, and lobes regions of the MB neurons. Adult-stage-specific knockdown of inx5 in αβ neurons disrupted ARM, suggesting a specific requirement of INX5 in αβ neurons for ARM formation. Hyperpolarization of αβ neurons during memory retrieval by expressing an engineered halorhodopsin (eNpHR) also disrupted ARM. Administration of the gap junction blocker carbenoxolone (CBX) reduced the proportion of odor responsive αβ neurons to the training odor 3 hours after training. Finally, the α-branch-specific 3-hour ARM-specific memory trace was also diminished with CBX treatment and in inx5 knockdown flies. Altogether, our results suggest INX5 gap junction channels in αβ neurons for ARM retrieval and also provide a more detailed neuronal mechanism for consolidated memory in Drosophila.

Associative olfactory memory in Drosophila has two components called labile anesthesia-sensitive memory and consolidated anesthesia-resistant memory (ARM). Mushroom body (MB) is a brain region critical for the olfactory memory and comprised of 2000 neurons that can be classified into αβ, α'β', and γ neurons. Previously we demonstrated that two parallel pathways mediated ARM consolidation: the serotonergic dorsal paired medial (DPM)-αβ neurons and the octopaminergic anterior paired lateral (APL)-α'β' neurons. This finding prompted us to ask how this composite ARM is retrieved. Here, we showed that blocking the output of αβ neurons and that of α'β' neurons each impaired ARM retrieval, and blocking both simultaneously had an additive effect. Knockdown of radish and octβ2R in αβ and α'β' neurons, respectively, impaired ARM. A combinatorial assay of radish mutant background rsh1 and neurotransmission blockade confirmed that ARM retrieved from α'β' neuron output is independent of radish. We identified MBON-β2β'2a and MBON-β'2mp as the MB output neurons downstream of αβ and α'β' neurons, respectively, whose glutamatergic transmissions also additively contribute to ARM retrieval. Finally, we showed that α'β' neurons could be functionally subdivided into α'β'm neurons required for ARM retrieval, and α'β'ap neurons required for ARM consolidation. Our work demonstrated that two parallel neural pathways mediating ARM consolidation in Drosophila MB additively contribute to ARM expression during retrieval.

The possible neurological and biophysical effects of magnetic fields on animals is an area of active study. Here, we report that courtship activity of male Drosophila increases in a magnetic field and that this effect is regulated by the blue light-dependent photoreceptor cryptochrome (CRY). Naïve male flies exhibited significantly increased courtship activities when they were exposed to a ≥ 20-Gauss static magnetic field, compared with their behavior in the natural environment (0 Gauss). CRY-deficient flies, cryb and crym, did not show an increased courtship index in a magnetic field. RNAi-mediated knockdown of cry in cry-GAL4-positive neurons disrupted the increased male courtship activity in a magnetic field. Genetically expressing cry under the control of cry-GAL4 in the CRY-deficient flies restored the increase in male courtship index that occurred in a magnetic field. Interestingly, artificially activating cry-GAL4-expressing neurons, which include large ventral lateral neurons and small ventral lateral neurons, via expression of thermosensitive cation channel dTrpA1, also increased the male courtship index. This enhancement was abolished by the addition of the cry-GAL80 transgene. Our results highlight the phenomenon of increased male courtship activity caused by a magnetic field through CRY-dependent magnetic sensation in CRY expression neurons in Drosophila.

Embrittlement induced by high-temperature tempering was investigated in two quenched-and-tempered offshore steels. Electron backscattering diffraction and analysis of Kernel average misorientation were applied to study the coalescence of martensite; transmission Kikuchi diffraction coupled with compositional mapping was used to characterize the martensite/austenite (M/A) phases. It is suggested that the formation of lenticular martensite along prior austenite grain boundaries or packet boundaries primarily explains the embrittlement in conventional S690Q steel, which has a higher carbon content. This embrittlement can be cured by additional heat treatment to decompose martensite into ferrite and cementite. In a newly designed NiCu steel with reduced carbon content, new lath martensite formed along interlath or inter-block boundaries of prior martensite. This microstructure is less detrimental to the impact toughness of the steel.

Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcers, and gastric cancer. Infection of cells with H. pylori is dependent on lipid rafts, which are cholesterol-rich microdomains located in the cell membrane. H. pylori cholesterol-α-glucosyltransferase (CGT) catalyzes the conversion of membrane cholesterol to cholesteryl glucosides, which can be incorporated into the bacterial cell wall, facilitating evasion from immune defense and colonization in the host. However, the detailed mechanisms underlying this process remain to be explored. In this study, we discovered for the first time that H. pylori CGT could promote adherence to gastric epithelial cells in a cholesterol-dependent manner. Externalization of cell membrane phosphatidylserine (PS) is crucial for enhancement of binding of H. pylori to cells by CGT and for cytotoxin-associated gene A (CagA)-induced pathogenesis. Furthermore, exogenous cholesterol interferes with the actions of H. pylori CGT to catalyze cellular cholesterol, which impedes bacterial binding to cells and attenuates subsequent inflammation, indicating that the initial attachment of H. pylori to cells is closely dependent on host cholesterol. These results provide evidence that CGT contributes to H. pylori infectivity and it may serve as a key target for the treatment of H. pylori-associated diseases. [ABSTRACT FROM AUTHOR]