Enhanced optical imaging and fluorescent labeling for visualizing drug molecules within living organisms.

The visualization of drugs in living systems has become key techniques in modern therapeutics. Recent advancements in optical imaging technologies and molecular design strategies have revolutionized drug visualization. At the subcellular level, super-resolution microscopy has allowed exploration of the molecular landscape within individual cells and the cellular response to drugs. Moving beyond subcellular imaging, researchers have integrated multiple modes, like optical near-infrared II imaging, to study the complex spatiotemporal interactions between drugs and their surroundings. By combining these visualization approaches, researchers gain supplementary information on physiological parameters, metabolic activity, and tissue composition, leading to a comprehensive understanding of drug behavior. This review focuses on cutting-edge technologies in drug visualization, particularly fluorescence imaging, and the main types of fluorescent molecules used. Additionally, we discuss current challenges and prospects in targeted drug research, emphasizing the importance of multidisciplinary cooperation in advancing drug visualization. With the integration of advanced imaging technology and molecular design, drug visualization has the potential to redefine our understanding of pharmacology, enabling the analysis of drug micro-dynamics in subcellular environments from new perspectives and deepening pharmacological research to the levels of the cell and organelles.

Association between loneliness and mild cognitive impairment in older adults: a meta-analysis of longitudinal studies.

OBJECTIVES: Prior studies reporting the effects of loneliness on mild impairment cognitive (MCI) have generated inconsistent results. This meta-analysis aimed to investigate the longitudinal association between loneliness and risk of MCI among community-dwelling middle-aged and older adults. METHOD: Five electronic databases were searched from inception to 9 May 2023. Eligible studies examined the longitudinal association between loneliness and cognitive outcomes, including incident MCI, cognitive impairment, and cognitive decline. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects meta-analysis. Sensitivity analysis and subgroup analysis were conducted. Publication bias was examined using Egger's and Begg tests. RESULTS: Eight studies were included. Among the 45,032 participants, 10,570 were diagnosed with MCI/cognitive decline. Loneliness was positively associated with an increased risk of MCI (overall OR = 1.14; 95% CI = 1.05, 1.23), with moderate heterogeneity (I2 = 44.2%). Sensitivity analysis have minimal influence on the aforementioned pooled effect. Subgroup analyses indicated stronger associations in studies which employed incident MCI as cognitive outcome (OR = 2.55, 95%CI = 1.31, 1.83), were conducted in non-Asia countries (OR = 1.52, 95%CI = 0.95, 1.20), and reported no depression adjustment (OR = 1.51, 95%CI = 1.04, 1.25). The association between loneliness and MCI was stronger among males compare to females. The Egger test and Begg test showed no evidence of significant publication bias (p = .493; p = .474). CONCLUSION: The findings indicated that loneliness was associated with an increased risk of MCI. Future longitudinal studies should evaluate potential cases of MCI through comprehensive clinical assessments by practitioners to draw robust findings on the association of loneliness with MCI.

Loneliness was associated with an increased risk of MCI in older adults.The association between loneliness and MCI was stronger in the males compared to the females.Future studies are warranted to assess loneliness by validated scales and clinical assessments of MCI.

Effect of surface electrode recording area on compound muscle action potential scan processing for motor unit number estimation.

Introduction: MScanFit is a model-based algorithm for motor unit number estimation (MUNE) from compound muscle action potential (CMAP) scan data. It is a clinically applicable tool because of its quick and automatic implementation. Electrodes with different recording areas were employed to record CMAP scan data in existing studies. However, the effect of electrode recording area on MScanFit MUNE and other CMAP scan parameters has not been studied. Methods: CMAP scan was performed on the abductor pollicis brevis muscle of both hands on 14 healthy subjects using three different electrodes with recording areas of 10 mm × 10 mm, 11 mm × 14 mm, and 22 mm × 26 mm, respectively. Motor unit number was estimated using MScanFit for each CMAP scan. Two motor unit number index parameters, i.e., D50 and step index (STEPIX), were also derived from the CMAP scan data. Results: No significant difference in D50, STEPIX, and MScanFit MUNE was observed across three different electrode recording areas, although the amplitude of CMAP decreased significantly when a larger electrode was used. Intraclass correlation coefficients of 0.792 and 0.782 were obtained for MScanFit MUNE and STEPIX, respectively. Discussion: Compared with CMAP amplitude, D50, STEPIX, and MScanFit MUNE are less sensitive to variation in electrode recording area. However, the repeatability of MScanFit MUNE could be compromised by the inconsistency in the electrode recording area.

PSAT1 mediated EMT of colorectal cancer cells by regulating Pl3K/AKT signaling pathway.

Background: The metastasis of colorectal cancer (CRC) is one of the significant barriers impeding its treated consequence and bring about high mortality, less surgical resection rate and poor prognosis of CRC patients. PSAT1 is an enzyme involved in serine biosynthesis. The studies showed that PSAT1 plays the part of a crucial character in the regulation of tumor metastasis. And Epithelial-Mesenchymal Transition (EMT) is a process of cell reprogramming in which epithelialcells obtain mesenchymal phenotypes. It is a crucial course in promoting cell metastasis and the progression of malignant tumors. The relationship between PSAT1 and EMT in colorectal cancer, as well as the underlying molecular mechanisms, remains enigmatic and warrants thorough exploration. These findings suggest that PSAT1 may serve as a promising therapeutic target for mitigating colorectal cancer metastasis and holds the potential to emerge as a valuable prognostic biomarker in forthcoming research endeavors. Materials and Methods: Utilizing TCGA dataset in conjunction with clinical CRC specimens, our initial focus was directed towards an in-depth examination of PSAT1 expression within CRC, specifically exploring its potential correlation with the adverse prognostic outcomes experienced by patients. Furthermore, we conducted a comprehensive investigation into the regulatory influence exerted by PSAT1 on CRC through the utilization of siRNA knockdown techniques. In the realm of in vitro experimentation, we meticulously evaluated the impact of PSAT1 on various facets of CRC progression, including cell migration, invasion, proliferation, and colony formation. In order to elucidate the intricate effects in question, we adopted a multifaceted methodology that encompassed a range of assays and analyses. These included wound healing assays, transwell assays, utilization of the Cell Counting Kit-8 (CCK-8) assay, and colony formation assays. By employing this diverse array of investigative techniques, we were able to achieve a comprehensive comprehension of the multifaceted role that PSAT1 plays in the pathogenesis of colorectal cancer. This multifarious analysis greatly contributed to our in-depth understanding of the complex mechanisms at play in colorectal cancer pathogenesis. Using WB and PCR experiments, we found that PSAT1 has a role in regulating EMT development in CRC.In terms of mechanism, we found that PSAT1 affected EMT by Regulating Pl3K/AKT Signaling Pathway. Results: Our investigation revealed a noteworthy down-regulation of PSAT1 expression in CRC specimens. Importantly, this down-regulation exhibited a significant positive correlation with the unfavorable prognosis of patients afflicted with CRC. Functionally, our study showcased that the siRNA-mediated knockdown of PSAT1 markedly enhanced various key aspects of CRC pathogenesis in an in vitro setting. Specifically, this included a substantial promotion of CRC cell migration, invasion, proliferation, and colony formation. Moreover, the silencing of PSAT1 also demonstrated a substantial promotion of the EMT process. Intriguingly, our research unveiled a hitherto unexplored mechanism underlying the regulatory role of PSAT1 in CRC and EMT. We have established, for the first time, that PSAT1 exerts its influence by modulating the activation of the PI3K/AKT Signaling Pathway. This mechanistic insight provides a valuable contribution to the understanding of the molecular underpinnings of CRC progression and EMT induction mediated by PSAT1. Conclusions: In unison, our research findings shed light on the previously uncharted and significant role of the PSAT1/PI3K/AKT axis in the initiation of the EMT process in CRC. Furthermore, our discoveries introduce a novel biomarker with potential implications for the clinical diagnosis and treatment of CRC.

Identifying Vulnerabilities to NSAID Adverse Events in the U.S. Population: An Analysis of Preexisting Conditions and Sex.

Purpose: In 2005, the Food and Drug Administration (FDA) issued a decision memorandum regarding nonsteroidal anti-inflammatory drugs (NSAIDs). The memorandum recommended the withdrawal of certain NSAIDs due to potential cardiovascular adverse effects. It highlighted the issue of cardiovascular risk associated with NSAIDs as a class. The NSAID medication guide includes a wide range of adverse drug reactions (ADRs), such as increased blood pressure, liver failure, allergic reactions, heart attack, and intestinal bleeding. Although both sexes have an increased risk of ADRs with NSAID use, females have a greater risk than males due to differences in pharmacodynamics and higher medication concentrations (mg/kg). In particular, females with high blood pressure, coronary heart, kidney, and liver disease are at an additional risk of harm from NSAID ADRs. This study quantifies sex-specific differences and other factors associated with prescription NSAID use. Method: The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES), a complex survey conducted by the Centers for Disease Control and Prevention (CDC) in two-year cycles. A survey-weighted logistic regression model was utilized to investigate potential sex differences with prescription NSAIDs in the context of other factors, including kidney disease, hypertension, liver disease, insurance status, coronary heart disease, and age, within the 2011-2018 NHANES survey data. Results: Females reported a slightly higher percentage of high blood pressure and kidney disease than males, while males reported a slightly higher percentage of coronary heart and liver disease than females. Last, the model indicated that females were 58% more likely to have used a prescription NSAID than males. Conclusion: The results confirm that women and people with medical conditions, who would potentially suffer greater harm from NSAID ADRs, are more likely to use a prescription NSAID than individuals without these conditions.

Connectome-driven neural inventory of a complete visual system.

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brain's volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing. To unravel the stunning diversity of a complex visual system, a careful mapping of the neural architecture matched to tools for targeted exploration of that circuitry is essential. Here, we report a new connectome of the right optic lobe from a male Drosophila central nervous system FIB-SEM volume and a comprehensive inventory of the fly's visual neurons. We developed a computational framework to quantify the anatomy of visual neurons, establishing a basis for interpreting how their shapes relate to spatial vision. By integrating this analysis with connectivity information, neurotransmitter identity, and expert curation, we classified the ~53,000 neurons into 727 types, about half of which are systematically described and named for the first time. Finally, we share an extensive collection of split-GAL4 lines matched to our neuron type catalog. Together, this comprehensive set of tools and data unlock new possibilities for systematic investigations of vision in Drosophila, a foundation for a deeper understanding of sensory processing.

Chemerin promotes invasion of oral squamous cell carcinoma by stimulating IL-6 and TNF-α production via STAT3 activation.

AIMS: Elevated levels of adipokine chemerin have been identified in oral squamous cell carcinoma (OSCC) and found to be associated with metastasis to the cervical lymph nodes. The underlying mechanism through which chemerin affects OSCC progression is unclear. The aims of this study were firstly to determine chemerin levels and cytokine concentrations in serum from patients with OSCC and in OSCC cell cultures, and secondly to observe chemerin effects on OSCC cell cytokine secretion, migration, and invasion in vitro. METHODS: Serum samples were collected from 20 patients diagnosed with OSCC, including groups with (LN+) and without (LN-) cervical lymph node metastasis. A Luminex liquid suspension assay was used to quantify serum concentrations of 27 types of cytokines. Correlations between chemerin and cytokines (i.e., IL-6, IL-15, GM-CSF, RANTES, TNF-α, and VEGF) were analyzed. ELISAs (enzyme-linked immunosorbent assays) were used to determine concentrations of chemerin and selected cytokines in serum and in supernatants of OSCC cell cultures (SCC9 and SCC25 cell lines). OSCC cells were stimulated with human recombinant chemerin, STAT3 inhibitor, or IL-6 together with TNF-α neutralizing antibodies. Phosphorylated STAT3 protein levels were measured with western blot analysis. OSCC cell migration and invasion were investigated with Transwell assays. RESULTS: Compared to the LN- group, OSCC patients with cervical lymph node metastasis had higher levels of IL-6 (P = 0.006), IL-15 (P = 0.020), GM-CSF (P = 0.036), RANTES (P = 0.032), TNF-α (P = 0.005), VEGF (P = 0.006), and chemerin (P = 0.001). Patients' serum chemerin levels correlated directly with IL-6, GM-CSF, TNF-α, and VEGF levels in OSCC patients. Exogenous recombinant chemerin treatment promoted secretion of IL-6 and TNF-α via activation of STAT3 in OSCC cells. Chemerin induced OSCC-cell migration and invasion, and these effects were reduced by IL-6 and TNF-α neutralizing antibodies. CONCLUSION: Our findings indicate that chemerin may play a role in advancing OSCC progression by increasing production of IL-6 and TNF-α, perhaps via a mechanism involving STAT3 signaling.

Phosphatase, Mg2+/Mn2+ dependent 1B regulates the hematopoietic stem cells homeostasis via the Wnt/ß-catenin signaling.

Hematopoietic stem cells (HSCs) are primarily dormant in a cell-cycle quiescence state to preserve their self-renewal capacity and long-term maintenance. How HSCs maintain the balance between activation and quiescence remains largely unknown. Herein, we found that Phosphatase, Mg2+/Mn2+ Dependent 1B (Ppm1b) is required for the expansion of phenotypic HSCs in vitro. By using a conditional knockout mouse model in which Ppm1b was specifically depleted in hematopoietic cells, we demonstrated that loss of Ppm1b impaired the HSC homeostasis and hematopoietic reconstitution. Ppm1b deficiency mice also exhibited B-cell leukocytopenia, which is due to the compromised commitment and proliferation of B-biased lymphoid progenitor cells from CLPs. With the aid of a small molecular inhibitor, we confirmed the roles of Ppm1b in adult hematopoiesis that phenocopied the effects with loss of Ppm1b. Furthermore, transcriptome profiling of Ppm1b-deficient HSCs revealed the disruptive quiescence of HSC. Mechanistically, Ppm1b interacted with ß-catenin and mediated its dephosphorylation. Loss of Ppm1b led to the decrease of the active ß- catenin (non-phosphorylated) that interrupted the Wnt/ß-catenin signaling in HSC, which consequently suppressed HSC expansion. Together, our study identified an indispensable role of Ppm1b in regulating HSC homeostasis via Wnt/ß-catenin pathway.

Effects of Quality Enhancement of Frozen Tuna Fillets Using Ultrasound-Assisted Salting: Physicochemical Properties, Histology, and Proteomics.

Salting pretreatment is an effective method to improve the quality of frozen fish. This study investigated the quality changes and proteomic profile differences of frozen yellowfin tuna fillets pretreated with ultrasound-assisted salting (UAS) and static salting (SS). This study was centered on three aspects: physicochemical indicators' determination, histological observation, and proteomic analysis. The results showed that UAS significantly increased yield, salt content, and water-holding capacity (WHC), decreased total volatile base nitrogen (TVBN) compared to SS (p < 0.05), and significantly increased water in the protein matrix within myofibrils. Histological observations showed that the tissue cells in the UAS group were less affected by frozen damage, with a more swollen structure and rougher surface of myofibrils observed. Furthermore, 4D label-free proteomics revealed 56 differentially abundant proteins (DAPs) in UAS vs. NT comparison, mainly structural proteins, metabolic enzymes, proteasomes, and their subunits, which are associated with metabolic pathways such as calcium signaling pathway, gap junction, actin cytoskeletal regulation, and necroptosis, which are intimately associated with quality changes in freeze-stored tuna fillets. In brief, UAS enhances the potential for the application of salting pretreatment to improve frozen meat quality, and 4D label-free proteomics provides knowledge to reveal the potential links between quality and molecular changes in processed frozen meat to optimize future UAS meat processing.

All-hydrocarbon stapling enables improvement of antimicrobial activity and proteolytic stability of peptide Figainin 2.

Figainin 2 is a cationic, hydrophobic, α-helical host-defense peptide with 28 residues, which was isolated from the skin secretions of the Chaco tree frog. It shows potent inhibitory activity against both Gram-negative and Gram-positive pathogens and has garnered considerable interest in developing novel classes of natural antibacterial agents. However, as a linear peptide, conformational flexibility and poor proteolytic stability hindered its development as antibacterial agent. To alleviate its susceptibility to proteolytic degradation and improve its antibacterial activity, a series of hydrocarbon-stable analogs of Figainin 2 were synthesized and evaluated for their secondary structure, protease stability, antimicrobial, and hemolytic activities. Among them, F2-12 showed significant improvement in protease resistance and antimicrobial activity compared to that of the template peptide. This study provides a promising strategy for the development of antimicrobial drugs.

A promising approach to steady-state fusion: High-temperature superconducting strong-field stellarator with precise omnigenity.

The stellarator has inherent advantages over the tokamak in achieving steady-state operation, especially due to its absence of disruptions and lack of need for current drive and the associated recirculating power. In recent years, there have been remarkable advances in the field of stellarator optimization, where precisely quasi-symmetric and precisely quasi-isodynamic magnetic configurations have been achieved with coils, allowing the neoclassical transport and energetic particle losses of stellarators to be reduced to levels comparable to those of tokamaks. At the same time, the development of high-temperature superconducting magnet technology will potentially double the magnetic field strength of stellarators. While these strong fields are expected to introduce new challenges, and while turbulent transport remains a common challenge for both stellarators and tokamaks, the combination of these physical and technological advances results in the expectation that stellarators will become a competitive approach to tokamaks for realizing steady-state fusion.

The Genomic Characteristics of an Arthritis-Causing Salmonella pullorum.

Salmonella enterica subsp. enterica serovar Gallinarum biovar pullorum (Salmonella pullorum) is an avian-specific pathogen that has caused considerable economic losses to the poultry industry. High endemicity, poor implementation of hygiene measures, and lack of effective vaccines hinder the prevention and control of this disease in intensively maintained poultry flocks. In recent years, the incidence of arthritis in chicks caused by Salmonella pullorum infection has increased. In this study, four Salmonella pullorum strains were identified from the livers, spleens, and joint fluids of Qingjiaoma chicken breeders with arthritis clinical signs, and an arthritis model of chicks was successfully established using SP206-2. Whole genome sequencing of the SP206-2 strain showed that the genome was 4,730,579 bp, 52.16% GC content, and contained 5007 genes, including 4729 protein-coding regions. The genomic analysis of four arthritis-causing isolates and three diarrhea-causing isolates showed that the genome of arthritis-causing isolates was subject to nonsynonymous mutations, shift mutations, and gene copy deletions. An SNP phylogenetic tree analysis showed that arthritis-causing isolates are located in a different evolutionary branch from diarrhea-causing isolates. Further differential genes analysis showed that the genome of arthritis-causing isolates had missense mutations in genes related to substance metabolism and substance transport, as a result of adaptive evolution.

Loss of the vitamin D receptor triggers senescence in chronic myeloid leukemia via DDIT4-mediated DNA damage.

Chronic myeloid leukemia (CML) is a hematopoietic malignancy driven by the fusion gene BCR: ABL1. Drug resistance to tyrosine kinase inhibitors (TKIs) due to BCR: ABL1 mutation and residual leukemia stem cells (LSCs) remain major challenges for CML treatment. Here, we revealed the requirement of VDR in the progression of CML, in which VDR was upregulated by BCR: ABL1, accounting for its high expression. Interestingly, VDR knockdown inhibited the CML cell proliferation driven by BCR: ABL1 regardless of its mutations with resistance to TKIs. Mechanistically, VDR transcriptionally regulated DDIT4 expression, and the inhibition of DDIT4 triggered DNA damage-induced senescence via p53 signaling activation in CML cells. Furthermore, VDR deficiency was sufficient to not only ameliorate the disease burden and progression in primary CML mice but also reduce the self-renewal of CML-LSCs. Together, our study demonstrated that targeting VDR is a promising strategy to overcome TKI resistance and eradicate leukemia stem cells in CML.

Monoterpene indole alkaloids from Gelsemium elegans.

Two new monoterpene indole alkaloids, Eleganine A (1) and Eleganine B (2), along with 11 known compounds (3-13) were isolated from the stems and leaves of Gelsemium elegans. Compound 1 is a gelsenicine-related monoterpenoid indole alkaloid possessing an iridoid unit. Their structures and absolute configurations of 1-2 were established by UV, IR, HR-ESI-MS, NMR spectroscopy, and electronic circular dichroism data analyses. All isolated compounds were evaluated for their anti-inflammatory and inhibiting glucose-induced mesanginal cell proliferation activities. None of them showed activity with IC50 far beyond 50 µM.

Monoterpene indole alkaloids from the roots of Alstonia rupestris and their anti-inflammatory activity.

Four new monoterpene indole alkaloids (1-4) together with twelve known alkaloids (5-16) were isolated from the roots of Alstonia rupestris. Compound 1 was the first example of C2-symmetric heteroyohimbine-type indole alkaloid homodimer obtained from natural plant resource. Their structures were elucidated on the basis of spectroscopic data. The absolute configuration of 1 was determined by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra. All compounds were evaluated for their anti-inflammatory activities by measuring their NO inhibitory effects in LPS-stimulated RAW 264.7 cells. Compound 2 showed strong NO inhibition with IC50 value of 4.2 ± 1.3 µM. Moreover, compound 2 could decrease the expressions of cyclooxygenase-2 (COX-2) and transforming growth factor beta-1 (TGF-ß1).

Sensitivity Analysis of CMAP Scan Step Index to Different Stimulation Parameters and Examination of Muscles Affected by Spinal Cord Injury.

Step index (STEPIX) is a recently developed compound muscle action potential (CMAP) scan method for evaluating motor unit loss and remodeling changes. This study investigates the influence of different stimulation parameters during CMAP scan on STEPIX and its examination of muscles affected by spinal cord injury (SCI). CMAP scan of the first dorsal interosseous (FDI) muscle was performed using different stimulus pulse widths (0.1 ms, 0.2 ms) and different numbers of stimuli (500, 1000) in 12 neurologically intact subjects. STEPIX was derived from each CMAP scan of all subjects. A significantly higher STEPIX was obtained using 1000 stimuli than 500 stimuli, while no significant difference in STEPIX was observed using 0.1 and 0.2 ms stimulus pulse widths. STEPIX was further applied to process CMAP scans of the FDI muscle from 13 tetraplegia and 13 healthy control subjects using the same stimulation parameter setting (0.1 ms, 500 stimuli), along with other methods including MScanFit motor unit number estimation (MUNE) and D50. STEPIX was significantly lower for the SCI subjects compared with the healthy control subjects. STEPIX was significantly correlated with MscanFit MUNE and D50, but had a smaller relative width of the overlapping zone (WOZ%) between tetraplegic and healthy control groups compared with MScanFit MUNE and D50. The findings of the study highlight the importance of maintaining a consistent stimulation parameter setting in CMAP scan studies and confirm the usefulness of STEPIX as a convenient CMAP scan parameter for examination of motor unit number changes.

IRDC-Net: An Inception Network with a Residual Module and Dilated Convolution for Sign Language Recognition Based on Surface Electromyography.

Deaf and hearing-impaired people always face communication barriers. Non-invasive surface electromyography (sEMG) sensor-based sign language recognition (SLR) technology can help them to better integrate into social life. Since the traditional tandem convolutional neural network (CNN) structure used in most CNN-based studies inadequately captures the features of the input data, we propose a novel inception architecture with a residual module and dilated convolution (IRDC-net) to enlarge the receptive fields and enrich the feature maps, applying it to SLR tasks for the first time. This work first transformed the time domain signal into a time-frequency domain using discrete Fourier transformation. Second, an IRDC-net was constructed to recognize ten Chinese sign language signs. Third, the tandem CNN networks VGG-net and ResNet-18 were compared with our proposed parallel structure network, IRDC-net. Finally, the public dataset Ninapro DB1 was utilized to verify the generalization performance of the IRDC-net. The results showed that after transforming the time domain sEMG signal into the time-frequency domain, the classification accuracy (acc) increased from 84.29% to 91.70% when using the IRDC-net on our sign language dataset. Furthermore, for the time-frequency information of the public dataset Ninapro DB1, the classification accuracy reached 89.82%; this value is higher than that achieved in other recent studies. As such, our findings contribute to research into SLR tasks and to improving deaf and hearing-impaired people's daily lives.

Comparative connectomics and escape behavior in larvae of closely related Drosophila species.

Evolution has generated an enormous variety of morphological, physiological, and behavioral traits in animals. How do behaviors evolve in different directions in species equipped with similar neurons and molecular components? Here we adopted a comparative approach to investigate the similarities and differences of escape behaviors in response to noxious stimuli and their underlying neural circuits between closely related drosophilid species. Drosophilids show a wide range of escape behaviors in response to noxious cues, including escape crawling, stopping, head casting, and rolling. Here we find that D. santomea, compared with its close relative D. melanogaster, shows a higher probability of rolling in response to noxious stimulation. To assess whether this behavioral difference could be attributed to differences in neural circuitry, we generated focused ion beam-scanning electron microscope volumes of the ventral nerve cord of D. santomea to reconstruct the downstream partners of mdIV, a nociceptive sensory neuron in D. melanogaster. Along with partner interneurons of mdVI (including Basin-2, a multisensory integration neuron necessary for rolling) previously identified in D. melanogaster, we identified two additional partners of mdVI in D. santomea. Finally, we showed that joint activation of one of the partners (Basin-1) and a common partner (Basin-2) in D. melanogaster increased rolling probability, suggesting that the high rolling probability in D. santomea is mediated by the additional activation of Basin-1 by mdIV. These results provide a plausible mechanistic explanation for how closely related species exhibit quantitative differences in the likelihood of expressing the same behavior.