An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. elegans and Cancer.

Metformin has utility in cancer prevention and treatment, though the mechanisms for these effects remain elusive. Through genetic screening in C. elegans, we uncover two metformin response elements: the nuclear pore complex (NPC) and acyl-CoA dehydrogenase family member-10 (ACAD10). We demonstrate that biguanides inhibit growth by inhibiting mitochondrial respiratory capacity, which restrains transit of the RagA-RagC GTPase heterodimer through the NPC. Nuclear exclusion renders RagC incapable of gaining the GDP-bound state necessary to stimulate mTORC1. Biguanide-induced inactivation of mTORC1 subsequently inhibits growth through transcriptional induction of ACAD10. This ancient metformin response pathway is conserved from worms to humans. Both restricted nuclear pore transit and upregulation of ACAD10 are required for biguanides to reduce viability in melanoma and pancreatic cancer cells, and to extend C. elegans lifespan. This pathway provides a unified mechanism by which metformin kills cancer cells and extends lifespan, and illuminates potential cancer targets. PAPERCLIP.

Distinct layers of BRD4-PTEFb reveal bromodomain-independent function in transcriptional regulation.

The BET family protein BRD4, which forms the CDK9-containing BRD4-PTEFb complex, is considered to be a master regulator of RNA polymerase II (Pol II) pause release. Because its tandem bromodomains interact with acetylated histone lysine residues, it has long been thought that BRD4 requires these bromodomains for its recruitment to chromatin and transcriptional regulatory function. Here, using rapid depletion and genetic complementation with domain deletion mutants, we demonstrate that BRD4 bromodomains are dispensable for Pol II pause release. A minimal, bromodomain-less C-terminal BRD4 fragment containing the PTEFb-interacting C-terminal motif (CTM) is instead both necessary and sufficient to mediate Pol II pause release in the absence of full-length BRD4. Although BRD4-PTEFb can associate with chromatin through acetyl recognition, our results indicate that a distinct, active BRD4-PTEFb population functions to regulate transcription independently of bromodomain-mediated chromatin association. These findings may enable more effective pharmaceutical modulation of BRD4-PTEFb activity.

Acute perturbation strategies in interrogating RNA polymerase II elongation factor function in gene expression.

The regulation of gene expression catalyzed by RNA polymerase II (Pol II) requires a host of accessory factors to ensure cell growth, differentiation, and survival under environmental stress. Here, using the auxin-inducible degradation (AID) system to study transcriptional activities of the bromodomain and extraterminal domain (BET) and super elongation complex (SEC) families, we found that the CDK9-containing BRD4 complex is required for the release of Pol II from promoter-proximal pausing for most genes, while the CDK9-containing SEC is required for activated transcription in the heat shock response. By using both the proteolysis targeting chimera (PROTAC) dBET6 and the AID system, we found that dBET6 treatment results in two major effects: increased pausing due to BRD4 loss, and reduced enhancer activity attributable to BRD2 loss. In the heat shock response, while auxin-mediated depletion of the AFF4 subunit of the SEC has a more severe defect than AFF1 depletion, simultaneous depletion of AFF1 and AFF4 leads to a stronger attenuation of the heat shock response, similar to treatment with the SEC inhibitor KL-1, suggesting a possible redundancy among SEC family members. This study highlights the usefulness of orthogonal acute depletion/inhibition strategies to identify distinct and redundant biological functions among Pol II elongation factor paralogs.

Ca2+-Stimulated AMPK-Dependent Phosphorylation of Exo1 Protects Stressed Replication Forks from Aberrant Resection.

Abnormal processing of stressed replication forks by nucleases can cause fork collapse, genomic instability, and cell death. Despite its importance, it is poorly understood how the cell properly controls nucleases to prevent detrimental fork processing. Here, we report a signaling pathway that controls the activity of exonuclease Exo1 to prevent aberrant fork resection during replication stress. Our results indicate that replication stress elevates intracellular Ca2+ concentration ([Ca2+]i), leading to activation of CaMKK2 and the downstream kinase 5' AMP-activated protein kinase (AMPK). Following activation, AMPK directly phosphorylates Exo1 at serine 746 to promote 14-3-3 binding and inhibit Exo1 recruitment to stressed replication forks, thereby avoiding unscheduled fork resection. Disruption of this signaling pathway results in excessive ssDNA, chromosomal instability, and hypersensitivity to replication stress inducers. These findings reveal a link between [Ca2+]i and the replication stress response as well as a function of the Ca2+-CaMKK2-AMPK signaling axis in safeguarding fork structure to maintain genome stability.

Transcriptional elongation control of hypoxic response.

The release of paused RNA polymerase II (RNAPII) from promoter-proximal regions is tightly controlled to ensure proper regulation of gene expression. The elongation factor PTEF-b is known to release paused RNAPII via phosphorylation of the RNAPII C-terminal domain by its cyclin-dependent kinase component, CDK9. However, the signal and stress-specific roles of the various RNAPII-associated macromolecular complexes containing PTEF-b/CDK9 are not yet clear. Here, we identify and characterize the CDK9 complex required for transcriptional response to hypoxia. Contrary to previous reports, our data indicate that a CDK9 complex containing BRD4 but not AFF1/4 is essential for this hypoxic stress response. We demonstrate that BRD4 bromodomains (BET) are dispensable for the release of paused RNAPII at hypoxia-activated genes and that BET inhibition by JQ1 is insufficient to impair hypoxic gene response. Mechanistically, we demonstrate that the C-terminal region of BRD4 is required for Polymerase-Associated Factor-1 Complex (PAF1C) recruitment to establish an elongation-competent RNAPII complex at hypoxia-responsive genes. PAF1C disruption using a small-molecule inhibitor (iPAF1C) impairs hypoxia-induced, BRD4-mediated RNAPII release. Together, our results provide insight into potentially targetable mechanisms that control the hypoxia-responsive transcriptional elongation.

Supplementing Cancer?

In this issue of Molecular Cell, Lin et al. (2018) report that chondroitin-4-sulfate, which is found in a common supplement meant to alleviate degenerative joint disorders, promotes the growth of BRAF V600E mutant melanoma. This study not only has implications for patient care but also sheds light on a novel mechanism for regulating phosphoinositide 3-kinase signaling.

LncRNA LUESCC promotes esophageal squamous cell carcinoma by targeting the miR-6785-5p/NRSN2 axis.

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent gastrointestinal malignancies with high mortality worldwide. Emerging evidence indicates that long noncoding RNAs (lncRNAs) are involved in human cancers, including ESCC. However, the detailed mechanisms of lncRNAs in the regulation of ESCC progression remain incompletely understood. LUESCC was upregulated in ESCC tissues compared with adjacent normal tissues, which was associated with gender, deep invasion, lymph node metastasis, and poor prognosis of ESCC patients. LUESCC was mainly localized in the cytoplasm of ESCC cells. Knockdown of LUESCC inhibited cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth in vivo. Mechanistic investigation indicated that LUESCC functions as a ceRNA by sponging miR-6785-5p to enhance NRSN2 expression, which is critical for the malignant behaviors of ESCC. Furthermore, ASO targeting LUESCC substantially suppressed ESCC both in vitro and in vivo. Collectively, these data demonstrate that LUESCC may exerts its oncogenic role by sponging miR-6785-5p to promote NRSN2 expression in ESCC, providing a potential diagnostic marker and therapeutic target for ESCC patients.

Coevolution of tandemly repeated hlips and RpaB-like transcriptional factor confers desiccation tolerance to subaerial Nostoc species.

Desert-inhabiting cyanobacteria can tolerate extreme desiccation and quickly revive after rehydration. The regulatory mechanisms that enable their vegetative cells to resurrect upon rehydration are poorly understood. In this study, we identified a single gene family of high light-inducible proteins (Hlips) with dramatic expansion in the Nostoc flagelliforme genome and found an intriguingly special convergence formed through four tandem gene duplication. The emerged four independent hlip genes form a gene cluster (hlips-cluster) and respond to dehydration positively. The gene mutants in N. flagelliforme were successfully generated by using gene-editing technology. Phenotypic analysis showed that the desiccation tolerance of hlips-cluster-deleted mutant decreased significantly due to impaired photosystem II repair, whereas heterologous expression of hlips-cluster from N. flagelliforme enhanced desiccation tolerance in Nostoc sp. PCC 7120. Furthermore, a transcription factor Hrf1 (hlips-cluster repressor factor 1) was identified and shown to coordinately regulate the expression of hlips-cluster and desiccation-induced psbAs. Hrf1 acts as a negative regulator for the adaptation of N. flagelliforme to the harsh desert environment. Phylogenetic analysis revealed that most species in the Nostoc genus possess both tandemly repeated Hlips and Hrf1. Our results suggest convergent evolution of desiccation tolerance through the coevolution of tandem Hlips duplication and Hrf1 in subaerial Nostoc species, providing insights into the mechanism of desiccation tolerance in photosynthetic organisms.

Polariton Microfluidics for Nonreciprocal Dragging and Reconfigurable Shaping of Polaritons.

Dielectric environment engineering is an efficient and general approach to manipulating polaritons. Liquids serving as the surrounding media of polaritons have been used to shift polariton dispersions and tailor polariton wavefronts. However, those liquid-based methods have so far been limited to their static states, not fully unleashing the promise offered by the mobility of liquids. Here, we propose a microfluidic strategy for polariton manipulation by merging polaritonics with microfluidics. The diffusion of fluids causes gradient refractive indices over microchannels, which breaks the symmetry of polariton dispersions and realizes the microfluidic analogue to nonreciprocal polariton dragging. Based on polariton microfluidics, we also designed a set of on-chip polaritonic elements to actively shape polaritons, including planar lenses, off-axis lenses, Janus lenses, bends, and splitters. Our strategy expands the toolkit for the manipulation of polaritons at the subwavelength scale and possesses potential in the fields of polariton biochemistry and molecular sensing.

One-to-Nine Single Spectroscopic Intelligent Probe for Risk Assessment of Multiple Metals in Drinking Water.

26% of the world's population lacks access to clean drinking water; clean water and sanitation are major global challenges highlighted by the UN Sustainable Development Goals, indicating water security in public water systems is at stake today. Water monitoring using precise instruments by skilled operators is one of the most promising solutions. Despite decades of research, the professionalism-convenience trade-off when monitoring ubiquitous metal ions remains the major challenge for public water safety. Thus, to overcome these disadvantages, an easy-to-use and highly sensitive visual method is desirable. Herein, an innovative strategy for one-to-nine metal detection is proposed, in which a novel thiourea spectroscopic probe with high 9-metal affinity is synthesized, acting as "one", and is detected based on the 9 metal-thiourea complexes within portable spectrometers in the public water field; this is accomplished by nonspecialized personnel as is also required. During the processing of multimetal analysis, issues arise due to signal overlap and reproducibility problems, leading to constrained sensitivity. In this innovative endeavor, machine learning (ML) algorithms were employed to extract key features from the composite spectral signature, addressing multipeak overlap, and completing the detection within 30-300 s, thus achieving a detection limit of 0.01 mg/L and meeting established conventional water quality standards. This method provides a convenient approach for public drinking water safety testing.

Time-varying metasurface driven broadband radar jamming and deceptions.

Conventional radar jamming and deception systems typically necessitate the custom design of complex circuits and algorithms to transmit an additional radio signal toward a detector. Consequently, they are often cumbersome, energy-intensive, and difficult to operate in broadband electromagnetic environment. With the ongoing trend of miniaturization of various devices and the improvement of radar system performance, traditional techniques no longer meet the requirements for broadband, seamless integration, and energy efficiency. Time-varying metasurfaces, capable of manipulating electromagnetic parameters in both temporal and spatial domains, have thus inspired many contemporary research studies to revisit established fields. In this paper, we introduce a time-varying metasurface driven radar jamming and deception system (TVM-RJD), which can perfectly overcome the aforementioned intrinsic challenges. Leveraging a programmable bias voltage, the TVM-RJD can alter the spectrum distribution of incident waves, thereby deceiving radar into making erroneous judgments about the target's location. Experimental outcomes affirm that the accuracy deviation of the TVM-RJD system is less than 0.368 meters, while achieving a remarkable frequency conversion efficiency of up to 96.67%. The TVM-RJD heralds the expansion into a wider application of electromagnetic spatiotemporal manipulation, paving the way for advancements in electromagnetic illusion, radar invisibility, etc.

Risk factors for acute kidney injury associated with intravenous vancomycin in neurosurgical inpatients: a retrospective study.

PURPOSE: Vancomycin (VAN) is widely used in neurosurgical patients for intracranial infections. We aimed to assess the incidence and risk factors for VAN-associated acute kidney injury (VA-AKI) in this population. METHODS: A case-control study of patients who treated with vancomycin in neurosurgery from January 2020 to December 2022 was conducted. Demographics and potential risk factors were collected. Multivariate logistic regression analyses were performed to identify risk factors for VA-AKI. AKI was defined according to the Kidney Disease Improving Global Outcomes Guidelines (KDIGO). RESULTS: A total of 345 patients participated with a VA-AKI incidence of 17.1% (59 cases). Among them, 15 patients had renal impairment (Stage 2 or higher), and 2 required dialysis. With univariate analysis and binary logistic regression analysis, we found that the use of mannitol (OR: 4.164; 95% CI: 1.606-10.792; P = 0.003), loop diuretics (OR: 3.371; 95% CI: 1.633-6.958; P = 0.001), three or more antimicrobial applications (OR: 3.623; 95% CI: 1.600-8.206; P = 0.002), diastolic blood pressure 80-89 mm Hg (OR: 5.532; 95% CI: 1.677-18.250; P = 0.005) and diastolic blood pressure ≥ 90 mm Hg (OR: 6.845; 95% CI: 1.518-30.866; P = 0.012) were independent risk factors for VA-AKI. In addition, according to the Youden Index, the trough concentration of vancomycin should not exceed 15.845 mg/L. CONCLUSION: The incidence of VA-AKI in neurosurgical patients was 17.1%. The concomitant use of mannitol and loop diuretics, along with higher diastolic blood pressure and the combined use of more than three antimicrobial agents, were associated with an increased risk of neurosurgical VA-AKI.

Design and synthesis of luotonin A-derived topoisomerase targeting scaffold with potent antitumor effect and low genotoxicity.

Conventional topoisomerase (Topo) inhibitors typically usually exert their cytotoxicity by damaging the DNAs, which exhibit high toxicity and tend to result in secondary carcinogenesis risk. Molecules that have potent topoisomerase inhibitory activity but involve less DNA damage provide more desirable scaffolds for developing novel chemotherapeutic agents. In this work, we broke the rigid pentacyclic system of luotonin A and synthesized thirty-three compounds as potential Topo inhibitors based on the devised molecular motif. Further investigation disclose that two compounds with the highest antiproliferation activity against cancer cells, 5aA and 5dD, had a distinct Topo I inhibitory mechanism different from those of the classic Topo I inhibitors CPT or luteolin, and were able to obviate the obvious cellular DNA damage typically associated with clinically available Topo inhibitors. The animal model experiments demonstrated that even in mice treated with a high dosage of 50 mg/kg 5aA, there were no obvious signs of toxicity or loss of body weight. The tumor growth inhibition (TGI) rate was 54.3 % when 20 mg/kg 5aA was given to the T24 xenograft mouse model, and 5aA targeted the cancer tissue precisely without causing damage to the liver and other major organs.

Smart nano generation of transgenic algae expressing white spot syndrome virus in shrimps for inner ear-oral infection treatments using the spotted hyena optimizer (SHO)-Long short-term memory algorithm.

Nanotechnology offers a promising avenue to amplify the effectiveness and precision of using transgenic algae in managing WSSV in shrimp by possibly crafting nano-carriers for targeted therapeutic agent delivery or modifying algae cells at a molecular level. Leveraging the capabilities of nano-scale interventions, this study could explore innovative means to manipulate cellular processes, control biological interactions, and enhance treatment efficacy while minimizing undesirable impacts in aquatic environments. The White Spot Syndrome Virus (WSSV) is a double-stranded DNA virus with a tail and rod form that belongs to theNimaviridaefamily. There is no workable way to manage this illness at the moment. This research proposes a new model based on the Long Short-Term Memory (LSTM) and Spotted Hyena Optimizer (SHO) method to control the inner ear-oral infection, utilizing transgenic algae (Chlamydomonas reinhardtii). It is pretty tricky to modify the weight matrix in LSTM. The output will be more accurate if the weight of the neurons is exact. Histological examinations and nested polymerase chain reaction (PCR) testing were performed on the challenged shrimp every 4 h to assess the degree of white spot disease. The SHO-LSTM has shown the highest accuracy and Roc value (98.12% and 0.93, respectively) and the lowest error values (MSE = 0.182 and MAE = 0.48). The hybrid optimized model improves the overall inner ear-oral linked neurological diseases detection ratio. Additionally, with the slightest technical complexity, it effectively controls the forecast factors required to anticipate the ENT. Algal cells were found to be particularly well-suited for inner ear-oral infections, and shrimps fed a transgenic line had the best survival ratio in WSSV infection studies, with 87% of the shrimp surviving. This shows that using this line would effectively stop the spread of WSSV in shrimp populations.

circACTA2 inhibits NLRP3 inflammasome-mediated inflammation via interacting with NF-κB in vascular smooth muscle cells.

circACTA2 derived from the smooth muscle α-actin gene plays an important role in the regulation of vascular smooth muscle cell (VSMC) phenotype. The activation of NLRP3 inflammasome is involved in VSMC phenotypic switching. However, the mechanistic relationship between circACTA2 and NLRP3 inflammasome during vascular remodeling remains poorly understood. Here, we showed that circACTA2 was down-regulated in human intimal hyperplasia. circACTA2 overexpression in circACTA2 transgenic mice significantly decreased the neointimal hyperplasia induced by vascular injury, which is concomitant with a decrease in IL-18, IL-1ß, TNF-α, and IL-6 levels. Gain- and loss-of-function studies revealed that circACTA2 alleviated VSMC inflammation by suppressing the activation of NLRP3 inflammasome. Mechanistically, circACTA2 inhibited the expression of NF-κB p65 and p50 subunits and interacted with p50, which impedes the formation of the p50/p65 heterodimer and nuclear translocation induced by TNF-α, thus resulting in the suppression of NLRP3 gene transcription and inflammasome activation. Furthermore, circACTA2 overexpression mitigated inflammation via repressing NLRP3 inflammasome-mediated VSMC pyroptosis. Importantly, employing a decoy oligonucleotide to compete with circACTA2 for binding to p50 could attenuate the expression of NLRP3, ASC, and caspase-1. These findings provide a novel insight into the functional roles of circACTA2 in VSMCs, and targeting the circACTA2-NF-κB-NLRP3 axis represents a promising therapeutic strategy for vascular remodeling.

Enhancing Inverted Internal Limiting Membrane Flap Stability in Macular Hole Retinal Detachment by the "Viscoelastic Agent Pool" Technique.

PURPOSE: To evaluate the surgical, anatomical, and functional results of "viscoelastic agent pool" technique-assisted stability of inverted internal limiting membrane flap in macular hole retinal detachment. METHODS: The innovative surgical technique was performed on 10 patients with macular hole retinal detachment. The primary outcomes included best-corrected visual acuity after surgery, rate of closure of macular hole, retinal reattachment, and occurrence of complications. RESULTS: The mean age of the individuals was 67.70 ± 8.75 (range, 55-84) years; mean axial length, 29.34 ± 1.53 (range, 27.10-30.93) mm; mean corrected MH diameter, 685.30± 345.65 (range, 172-1,325) µ m; and average follow-up period, 6.01 ± 1.71 (range, 3.10-8.4) months. In 6 eyes (60%), the postoperative best-corrected visual acuity showed improvement. All patients had macular hole closure, and the retinal reattachment rate was 100%. No postoperative complications were noted. CONCLUSION: The "viscoelastic agent pool" technique, an innovative surgical approach designed to enhance the stability of the internal limiting membrane flap, serves as an effective adjunctive procedure for the inverted internal limiting membrane flap technique. It presents a viable option for patients with macular hole retinal detachment.

"Multidisciplinary fast-track" care can significantly reduce risk of mortality among hip fracture patients at least 80 years old: a single-center retrospective study.

BACKGROUND: "Multidisciplinary fast-track" (MFT) care can accelerate recovery and improve prognosis after surgery, but whether it is effective in older people after hip fracture surgery is unclear. METHODS: We retrospectively compared one-year all-cause mortality between hip fracture patients at least 80 years old at our institution who underwent hip fracture surgery between January 2014 and December 2018 and who then received MFT or conventional care. Multivariable regression was used to assess the association between MFT care and mortality after adjustment for confounders. RESULTS: The final analysis included 247 patients who received MFT care and 438 who received conventional orthopedic care. The MFT group showed significantly lower one-year mortality (8.9% vs. 14.4%, P = 0.037). Log-rank testing of Kaplan-Meier survival curves confirmed the survival advantage. However, the two groups did not differ significantly in rates of mortality during hospitalization or at 30 or 90 days after surgery. Regression analysis confirmed that MFT care was associated with lower risk of one-year mortality (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.281-0.788, P = 0.04), and the survival benefit was confirmed in subgroups of patients with anemia (HR 0.453, 95% CI 0.268-0.767, P = 0.003) and patients with American Society of Anesthesiologists grade III (HR 0.202, 95% CI 0.08-0.51, P = 0.001). CONCLUSIONS: MFT care can reduce one-year mortality among hip fracture patients at least 80 years old. This finding should be verified and extended in multi-center randomized controlled trials.

Risk assessment of imported malaria in China: a machine learning perspective.

BACKGROUND: Following China's official designation as malaria-free country by WHO, the imported malaria has emerged as a significant determinant impacting the malaria reestablishment within China. The objective of this study is to explore the application prospects of machine learning algorithms in imported malaria risk assessment of China. METHODS: The data of imported malaria cases in China from 2011 to 2019 was provided by China CDC; historical epidemic data of malaria endemic country was obtained from World Malaria Report, and the other data used in this study are open access data. All the data processing and model construction based on R, and map visualization used ArcGIS software. RESULTS: A total of 27,088 malaria cases imported into China from 85 countries between 2011 and 2019. After data preprocessing and classification, clean dataset has 765 rows (85 * 9) and 11 cols. Six machine learning models was constructed based on the training set, and Random Forest model demonstrated the best performance in model evaluation. According to RF, the highest feature importance were the number of malaria deaths and Indigenous malaria cases. The RF model demonstrated high accuracy in forecasting risk for the year 2019, achieving commendable accuracy rate of 95.3%. This result aligns well with the observed outcomes, indicating the model's reliability in predicting risk levels. CONCLUSIONS: Machine learning algorithms have reliable application prospects in risk assessment of imported malaria in China. This study provides a new methodological reference for the risk assessment and control strategies adjusting of imported malaria in China.

Increased team familiarity for surgical time savings: Effective primarily in complex surgical cases.

BACKGROUND: Cohesion between team members is critical for surgical performance. Our previous study has shown that the experience of working together (measured by Team Familiarity Score, TFS) helps reduce procedure time (PT). However, that conclusion was found in a relatively small sample size. With a large dataset including mixed general surgical procedures, we hypothesize that team familiarity makes a significant contribution to the improvement of team performance in complex cases, rather than in medium or basic surgical cases, measured by the procedure time, length of hospital stays (LOS), and surgical cost (COST). STUDY DESIGN: Patient demographics, operation, and patient outcome data of 922 general surgery cases were included. The cases were divided into three subgroups, including basic, medium, and complex surgical procedures. TFS and an Index of Difficulty of Surgery (IDS) were calculated for each procedure. Simple linear regression and random forest regressions were performed to analyze the association between surgical outcomes and all included independent variables (TFS, IDS, patient age, patient weight, and team size). RESULTS: When applied to complex cases, procedure time (r = -0.21) and cost (r = -0.23) dropped as TFS increases. In basic and medium surgical cases, increasing team familiarity failed to shorten the procedure time on average. CONCLUSION: Team familiarity is more important in complex cases because there is greater potential for improvement through team collaboration compared to basic and medium cases. Caution will be needed when applying team familiarity scores for examining surgical team performance in large databases with skewed to basic surgical cases.

Quantifying the Impact of Motions on Human Aiming Performance: Evidence from Eye Tracking and Bio-Signals.

Working on a moving platform can significantly impede human performance. Previous studies on moving vehicles have often focused on the overall impact on general task performance, whereas our study's emphasis is on precise hand movements, exploring the interaction between body motion and the escalation of task difficulty. We recruited 28 participants to engage in reciprocal aiming tasks, following Paul Fitts's setting, under both in-motion and stationary conditions. The task index of difficulty (ID) was manipulated by varying the width of the targets and the distance between the targets. We measured participants' movement time (MT), performance errors, and monitored their eye movements using an eye-tracking device, heart rate (HR), and respiration rate (RR) during the tasks. The measured parameters were compared across two experimental conditions and three ID levels. Compared to the stationary conditions, the in-motion conditions degraded human aiming performance, resulting in significantly prolonged MT, increased errors, and longer durations of eye fixations and saccades. Furthermore, HR and RR increased under the in-motion conditions. Linear relationships between MT and ID exhibited steeper slopes under the in-motion conditions compared to the stationary conditions. This study builds a foundation for us to explore the control mechanisms of individuals working in dynamic and demanding environments, such as pilots in airplanes and paramedics in ambulances.