Lycium barbarum pulp addition improves the dough properties and gluten protein structure.

This study investigated the effects of Lycium barbarum pulp (LBP) on the properties of mixed dough and gluten protein. The results showed that appropriate addition of LBP (5 %) significantly improved the performance of the dough, promoted the aggregation of gluten protein, enhanced the water binding ability, and delayed the gelatinization of starch during cooking. Compared with the control group, the peak temperature (Tp) of the LBP sample gradually increased from 63.23 °C to 65.56 °C, the expansion force reduced by about 21.56 %, the absolute Zeta potential lowered by about 18.4 %, and the α -helix content and ß -folding increased by 32.36 % and 10.23 %, respectively, indicating the more orderly and stable overall structure. However, LBP did not change the crystal configuration of starch and still showed typical type A line diffraction. Moreover, the addition of LBP increased the polyphenol content, which further improved the antioxidant properties and provided the possibility to improve the health potential of the flour.

Causal Associations Between Tea Consumption and REM Sleep Behavior Disorder: A Mendelian Randomization Study.

BACKGROUND: Previous studies have shown that tea consumption may have a protective effect against neurodegenerative diseases. However, the exact causal relationship between tea consumption and the precursor stages of certain neurodegenerative diseases, namely REM sleep behavior disorder (RBD), remains unclear. To evaluate the causal association between tea consumption and RBD, we employed a Mendelian randomization study. METHODS: We identified genetic instrumental variables that are significantly associated with tea consumption through genome-wide association studies (GWAS) in European populations. Bidirectional two-sample Mendelian randomization was utilized to determine the causal relationship between tea consumption and RBD, while sensitivity analyses were further employed to evaluate the robustness of the results. The multivariate Mendelian randomization method was used to assess the influence of relevant confounding factors on the results. RESULTS: In the MR analysis using the inverse variance weighting method, a significant causal relationship between tea consumption and RBD was observed (OR=0.046, 95% CI 0.004-0.563, p=0.016). The consistency of findings across maximum likelihood, MR PRESSO, and multivariate MR after adjusting for potential confounding further supports this causal association. Sensitivity analyses revealed no evidence of heterogeneity or pleiotropy. CONCLUSIONS: The findings of our study demonstrate a robust causal association between tea consumption and RBD, indicating that tea consumption may serve as a protective factor against the development of RBD.

A biomimic anti-neuroinflammatory nanoplatform for active neutrophil extracellular traps targeting and spinal cord injury therapy.

Traumatic spinal cord injury (SCI) always leads to severe neurological deficits and permanent damage. Neuroinflammation is a vital process of SCI and have become a promising target for SCI treatment. However, the neuroinflammation-targeted therapy would hinder the functional recovery of spinal cord and lead to the treatment failure. Herein, a biomimic anti-neuroinflammatory nanoplatform (DHCNPs) was developed for active neutrophil extracellular traps (NETs) targeting and SCI treatment. The curcumin-loaded liposome with the anti-inflammatory property acted as the core of the DHCNPs. Platelet membrane and neutrophil membrane were fused to form the biomimic hybrid membrane of the DHCNPs for hijacking neutrophils and neutralizing the elevated neutrophil-related proinflammatory cytokines, respectively. DNAse I modification on the hybrid membrane could achieve NETs degradation, blood spinal cord barrier, and neuron repair. Further studies proved that the DHCNPs could reprogram the multifaceted neuroinflammation and reverse the SCI process via nuclear factor kappa-B (NF-κB) pathway. We believe that the current study provides a new perspective for neuroinflammation inhibition and may shed new light on the treatment of SCI.

Protonation State-Induced Unfolding of Protein Secondary Structure in the Gas Phase.

The combination of infrared spectroscopy (IR) and ion mobility mass spectrometry (IM-MS) has revealed that protein secondary structures are retained upon transformation from aqueous solution to the gas phase under gentle conditions. Yet the details about where and how these structural elements are embedded in the gas phase remain elusive. In this study, we employ long time scale molecular dynamics (MD) simulations to examine the extent to which proteins retain their solution structures and the impact of protonation state on the stability of secondary structures in the gas phase. Our investigation focuses on two well-studied proteins, myoglobin and ß-lactoglobulin, representing typical helical and ß-sheet proteins, respectively. Our simulations accurately reproduce the experimental collision cross section (CCS) data measured by IM-MS. Based on accurately reproducing previous experimental collision cross section data and dominant secondary structural species obtained from IM-MS and IR, we confirm that both proteins largely retain their native secondary structural components upon passing from aqueous solution to the gas phase. However, we observe significant reductions in secondary structure contents (19.2 ± 1.2% for myoglobin and 7.3 ± 0.6% for ß-lactoglobulin) in specific regions predominantly composed of ionizable residues. Further mechanistic analysis suggests that alterations in protonation states of these residues after phase transition induce changes in their local interaction networks and backbone dihedral angles, which potentially promote the unfolding of secondary structures in the gas phase. We anticipate that similar protonation state induced unfolding may be observed in other proteins possessing distinct secondary structures. Further studies on a broader array of proteins will be essential to refine our understanding of protein structural behavior during the transition to the gas phase.

Robust Collaborative Visual-Inertial SLAM for Mobile Augmented Reality.

Achieving precise real-time localization and ensuring robustness are critical challenges in multi-user mobile AR applications. Leveraging collaborative information to augment tracking accuracy on lightweight devices and fortify overall system robustness emerges as a crucial necessity. In this paper, we propose a robust centralized collaborative rnulti-agent VI-SLAM system for mobile AR interaction and server-side efficient consistent mapping. The system deploys a lightweight VIO frontend on mobile devices for real-time tracking, and a backend running on a remote server to update multiple submaps. When overlapping areas between submaps across agents are detected, the system performs submap fusion to establish a globally consistent map. Additionally, we propose a map registration and fusion strategy based on covisibility areas for online registration and fusion in multi-agent scenarios. To improve the tracking accuracy of the frontend on agent, we introduce a strategy for updating the global map to the local map at a moderate frequency between the camera-rate pose estimation of the frontend VIO and the low-frequency global map optimization, using a tightly coupled strategy to achieve consistency of the multi-agent frontend poses estimation in the global map. The effectiveness of the proposed method is further confirmed by executing backend mapping on the server and deploying VIO frontends on multiple mobile devices for AR demostration. Additionally, we discuss the scalability of the proposed system by analyzing network traffic, synchronization frequency, and other factors at both the agent and server ends.

Elastase-targeting biomimic nanoplatform for neurovascular remodeling by inhibiting NETosis mediated AlM2 inflammasome activation in ischemic stroke.

Neutrophil elastase (NE) is a protease released by activated neutrophils in the brain parenchyma after cerebral ischemia, which plays a pivotal role in the regulation of neutrophil extracellular traps (NETs) formation. The excess NETs could lead to blood-brain barrier (BBB) breakdown, overwhelming neuroinflammation, and neuronal injury. While the potential of targeting neutrophils and inhibiting NE activity to mitigate ischemic stroke (IS) pathology has been recognized, effective strategies that inhibit NETs formation remain under-explored. Herein, a biomimic multifunctional nanoplatform (HM@ST/TeTeLipos) was developed for active NE targeting and IS treatment. The core of the HM@ST/TeTeLipos consisted of sivelestat-loaded ditelluride-containing liposomes with ROS-responsive and NE-inhibiting properties. The outer shell was composed of platelet-neutrophil hybrid membrane vesicles (HMVs), which acted to hijack neutrophils and neutralize proinflammatory cytokines. Our studies revealed that HM@ST/TeTeLipos could effectively inhibit NE activity, thereby suppressing the release of NETs, impeding the activation of the AIM2 inflammasome, and consequently redirecting the immune response away from a pro-inflammatory M1 microglia phenotype. This resulted in enhanced neurovascular remodeling, reduced BBB disruption, and diminished neuroinflammation, ultimately promoting neuron survival. We believe that this innovative approach holds significant potential for improving the treatment of IS and various NE-mediated inflammatory diseases.

The Role of miRNA in Hyperthyroidism Induced by Excessive Iodine in Drinking Water.

In recent years, iodine deficiency-related diseases have been effectively controlled; the prevalence of excessive iodine-induced thyroid diseases has increased, such as hyperthyroidism. However, there are still several controversial outcomes regarding the relationship between excessive iodine intakes and hyperthyroidism. MicroRNAs (miRNAs) extensively participate in the progression of thyroid diseases; nevertheless, the relationship and mechanism between iodine exposure and miRNAs have not been explored in hyperthyroidism patients. In this study, a total of 308 pairs of hyperthyroidism patients and healthy controls were enrolled in. Logistic regression analysis showed that level of water iodine >100 µg/L was an independent risk factor for hyperthyroidism. Compared with the healthy control, the serum thyroglobulin (Tg) content and levels of interferon-γ (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly elevated in hyperthyroidism patients. Further, high-throughput miRNA sequencing was applied to find crucial miRNAs involved in the occurrence of hyperthyroidism related to excessive water iodine. Based on the fold change and Q value, miR-144-3p, miR-204-5p, miR-346, miR-23b-5p, and miR-193b-3p were selected for validation by qRT-PCR. Our results showed that miR-346 and miR-204-5p in the case group were significantly lower than those of the control group, and the similar results found under the level of water iodine >300 µg/L. Nonetheless, no significant difference was found at 10-100 µg/L level of water iodine. Furthermore, the ROC curve indicated that miR-346 and miR-204-5p had the ability to diagnose hyperthyroidism patients. Taken together, excessive water iodine may decrease the expression of miR-346 and miR-204-5p, which mediate the elevation of Tg and cytokines, ultimately making contribution to the development of hyperthyroidism.

Walrycin B, as a novel separase inhibitor, exerts potent anticancer efficacy in a mouse xenograft model.

Proper chromosome segregation during cell division relies on the timely dissolution of chromosome cohesion. Separase (EC3.4.22.49), a cysteine protease, plays a critical role in mitosis by cleaving the kleisin subunit of cohesin, thereby presenting a promising target for cancer therapy. However, challenges in isolating active human separase suitable for high-throughput screening have limited the identification of effective inhibitors. Here, we conducted a high-throughput screening of small-molecule inhibitors using the protease domain of Chaetomium thermophilum separase (ctSPD), which not only shares significant sequence similarity with human separase but is also readily available. After conducting a primary screening of a library containing 9,172 compounds and subsequent validation using human separase, we identified walrycin B and its analogs, toxoflavin, 3-methyltoxoflavin, and 3-phenyltoxoflavin, as potent inhibitors of human separase. Subsequent microscale thermophoresis assays and molecular dynamics simulations revealed that walrycin B binds to the active site of separase and competes with substrates for binding. Additionally, cell-based studies showed that walrycin B and its analogs effectively induce cell cycle arrest at the M phase, activate apoptosis, and ultimately lead to cell death in mitosis. Finally, in a mouse xenograft model, walrycin B exhibited significant antitumor efficacy with minimal side effects. Together, these findings highlight the therapeutic potential of walrycin B for cancer treatment and its utility as a chemical tool in future studies involving separase.

Sensitivity of triple negative breast cancer cells to ATM-dependent ferroptosis induced by sodium selenite.

Targeting ferroptosis, a type of cell death elicited by Fe2+ and lipid reactive oxygen species (L-ROS), provides a novel strategy for cancer therapy. Selenium has the potential to treat cancers by acting as a pro-oxidative agent, thus leading to cancer cell death. Here, we found that the triple negative breast cancer (TNBC) MDA-MB-231 cells were more sensitive to ferroptosis induced by sodium selenite (Na2SeO3) than that of non-TNBC MCF-7 cells. Na2SeO3 significantly elevated the level of L-ROS, MDA and Fe2+, decreased the content of GSH and the enzyme activity of GPx, disrupted the expression of ferroptosis related proteins such as GPx4 and FTH1, as well as compromised mitochondrial morphology in MDA-MB-231 cells. Moreover, ATM was activated by Na2SeO3 in MDA-MB-231 cells. Notably, Na2SeO3-induced ferroptosis was inhibited by ATM kinase inhibitor KU55933 or siATM, suggesting that Na2SeO3-induced ferroptosis was mediated by ATM protein in MDA-MB-231 cells. Our findings suggest a therapeutic strategy by ferroptosis against TNBC and deepened our understanding of ATM function.

Angiopep-2 conjugated biomimetic nano-delivery system loaded with resveratrol for the treatment of methamphetamine addiction.

Methamphetamine (METH) addiction can damage the central nervous system, resulting in cognitive impairment and memory deficits. Low target effects have limited the utility of anti-addiction drugs because the presence of the blood-brain barrier hinders the effective delivery of drugs to the brain. Angiopep-2 can recognize and target low-density lipoprotein receptor-associated protein 1 (LRP-1) on the surface of cerebral capillary endothelial cells, causing cross-cell phagocytosis, and thus has high blood-brain barrier transport capacity. Resveratrol (RSV) has been found to be a neuroprotective agent in many nervous system diseases. In our study, we modified Angiopep-2 on the surface of the erythrocyte membrane to obtain a modified erythrocyte membrane (Ang-RBCm) and coated RSV-loaded poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG) nanoparticles with Ang-RBCm (Ang-RBCm@RSVNPs) to treat METH addiction. Our results showed that Ang-RBCm@RSVNPs can penetrate the blood-brain barrier and accumulate in the brain better than free RSV. Besides, mice treatetd with Ang-RBCm@RSVNPs showed less preference to METH-paired chamber and no noticeable tissue toxicity or abnormality was found in H&E staining images. Electrophysiological experiments demonstrated Ang-RBCm@RSVNPs could elevate synaptic plasticity impaired by METH. These indicated that Ang-RBCm@RSVNPs has better anti-addiction and neuroprotective effects. Therefore, Ang-RBCm@RSVNPs has great potential in the treatment of METH addiction.

Intelligent Cockpits for Connected Vehicles: Taxonomy, Architecture, Interaction Technologies, and Future Directions.

Highly integrated information sharing among people, vehicles, roads, and cloud systems, along with the rapid development of autonomous driving technologies, has spurred the evolution of automobiles from simple "transportation tools" to interconnected "intelligent systems". The intelligent cockpit is a comprehensive application space for various new technologies in intelligent vehicles, encompassing the domains of driving control, riding comfort, and infotainment. It provides drivers and passengers with safety, comfort, and pleasant driving experiences, serving as the gateway for traditional automobile manufacturing to upgrade towards an intelligent automotive industry ecosystem. This is the optimal convergence point for the intelligence, connectivity, electrification, and sharing of automobiles. Currently, the form, functions, and interaction methods of the intelligent cockpit are gradually changing, transitioning from the traditional "human adapts to the vehicle" viewpoint to the "vehicle adapts to human", and evolving towards a future of natural interactive services where "humans and vehicles mutually adapt". This article reviews the definitions, intelligence levels, functional domains, and technical frameworks of intelligent automotive cockpits. Additionally, combining the core mechanisms of human-machine interactions in intelligent cockpits, this article proposes an intelligent-cockpit human-machine interaction process and summarizes the current state of key technologies in intelligent-cockpit human-machine interactions. Lastly, this article analyzes the current challenges faced in the field of intelligent cockpits and forecasts future trends in intelligent cockpit technologies.

Tailored endothelialization enabled by engineered endothelial cell vesicles accelerates remodeling of small-diameter vascular grafts.

Current gold standard for the replacement of small-diameter blood vessel (ID < 4 mm) is still to utilize the autologous vessels of patients due to the limitations of small-diameter vascular grafts (SDVG) on weak endothelialization, intimal hyperplasia and low patency. Herein, we create the SDVG with the tailored endothelialization by applying the engineered endothelial cell vesicles to camouflaging vascular grafts for the enhancement of vascular remodeling. The engineered endothelial cell vesicles were modified with azide groups (ECVs-N3) through metabolic glycoengineering to precisely link the vascular graft made of PCL-DBCO via click chemistry, and thus fabricating ECVG (ECVs-N3 modified SDVG), which assists inhibition of platelet adhesion and activation, promotion of ECs adhesion and enhancement of anti-inflammation. Furthermore, In vivo single-cell transcriptome analysis revealed that the proportion of ECs in the cell composition of ECVG surpassed that of PCL, and the tailored endothelialization enabled to convert endothelial cells (ECs) into some specific ECs clusters. One of the specific cluster, Endo_C5 cluster, was only detected in ECVG. Consequently, our study integrates the engineered membrane vesicles of ECVs-N3 from native ECs for tailored endothelialization on SDVG by circumventing the limitations of living cells, and paves a new way to construct the alternative endothelialization in vessel remodeling following injury.

Water-medicated specifically targeting the S1 pockets among serine proteases using an arginine analogue.

Because of the high similarity in structure and sequence, it is challenging to distinguish the S1 pocket among serine proteases, primarily due to the only variability at residue 190 (A190 and S190). Peptide or protein-based inhibitors typically target the negatively charged S1 pocket using lysine or arginine as the P1 residue, yet neither discriminates between the two S1 pocket variants. This study introduces two arginine analogues, L-4-guanidinophenylalanine (12) and L-3-(N-amidino-4-piperidyl)alanine (16), as novel P1 residues in peptide inhibitors. 16 notably enhances affinities across all tested proteases, whereas 12 specifically improved affinities towards proteases possessing S190 in the S1 pocket. By crystallography and molecular dynamics simulations, we discovered a novel mechanism involving a water exchange channel at the bottom of the S1 pocket, modulated by the variation of residue 190. Additionally, the specificity of 12 towards the S190-presenting S1 pocket is dependent on this water channel. This study not only introduces novel P1 residues to engineer inhibitory potency and specificity of peptide inhibitors targeting serine proteases, but also unveils a water-mediated molecular mechanism of targeting serine proteases.

Comparison of clinical outcomes and perinatal outcomes between natural cycle and hormone replacement therapy of frozen-thawed embryo transfer in patients with regular menstruation: a propensity score-matched analysis.

Purpose: To investigate potential differences in pregnancy outcomes among patients with regular menstruation who underwent frozen-thawed embryo transfer using natural cycle (NC) or hormone replacement therapy (HRT). Methods: This study retrospectively analyzed 2672 patients with regular menstruation who underwent FET from November 2015 to June 2021 at the single reproductive medical center. A one-to-one match was performed applying a 0.02 caliper with propensity score matching. Independent factors influencing the live birth and clinical pregnancy rates were screened and developed in the nomogram by logistic regression analysis. The efficacy of live birth rate and clinical pregnancy rate prediction models was assessed with the area under the ROC curve, and the live birth rate prediction model was internally validated within the bootstrap method. Results: The NC protocol outperformed the HRT protocol in terms of clinical pregnancy and live birth rates. The stratified analysis revealed consistently higher live birth and clinical pregnancy rates with the NC protocol across different variable strata compared to the HRT protocol. However, compared to the HRT treatment, perinatal outcomes indicated that the NC protocol was related to a higher probability of gestational diabetes. Multifactorial logistic regression analysis demonstrated independent risk factors for live birth rate and clinical pregnancy rate. To predict the two rates, nomogram prediction models were constructed based on these influencing factors. The receiver operating characteristic curve demonstrated moderate predictive ability with an area under curve (AUC) of 0.646 and 0.656 respectively. The internal validation of the model for live birth rate yielded an average AUC of 0.646 implying the stability of the nomogram model. Conclusion: This study highlighted that NC yielded higher live birth and clinical pregnancy rates in comparison to HRT in women with regular menstruation who achieved successful pregnancies through frozen-thawed embryo transfer. However, it might incur a higher risk of developing gestational diabetes.

Spleen volume is associated with overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with portal hypertension.

BACKGROUND: Portal shunt and immune status related to the spleen are related to the occurrence of hepatic encephalopathy (HE). It is unknown whether spleen volume before transjugular intrahepatic portosystemic shunt (TIPS) is related to postoperative HE. AIM: To investigate the relationship between spleen volume and the occurrence of HE. METHODS: This study included 135 patients with liver cirrhosis who underwent TIPS, and liver and spleen volumes were elevated upon computed tomography imaging. The Kaplan-Meier curve was used to compare the difference in the incidence rate of HE among patients with different spleen volumes. Univariate and multivariate Cox regression analyses were performed to identify the factors affecting overt HE (OHE). Restricted cubic spline was used to examine the shapes of the dose-response association between spleen volumes and OHE risk. RESULTS: The results showed that 37 (27.2%) of 135 patients experienced OHE during a 1-year follow-up period. Compared with preoperative spleen volume (901.30 ± 471.90 cm3), there was a significant decrease in spleen volume after TIPS (697.60 ± 281.0 cm3) in OHE patients. As the severity of OHE increased, the spleen volume significantly decreased (P < 0.05). Compared with patients with a spleen volume ≥ 782.4 cm3, those with a spleen volume < 782.4 cm3 had a higher incidence of HE (P < 0.05). Cox regression analysis showed that spleen volume was an independent risk factor for post-TIPS OHE (hazard ratio = 0.494, P < 0.05). Restricted cubic spline model showed that with an increasing spleen volume, OHE risk showed an initial increase and then decrease (P < 0.05). CONCLUSION: Spleen volume is related to the occurrence of OHE after TIPS. Preoperative spleen volume is an independent risk factor for post-TIPS OHE.

Sialylation-induced stabilization of dynamic glycoprotein conformations unveiled by time-aligned parallel unfolding and glycan release mass spectrometry.

Sialylation, a critical post-translational modification, regulates glycoprotein structure and function by tuning their molecular heterogeneity. However, characterizing its subtle and dynamic conformational effects at the intact glycoprotein level remains challenging. We introduce a glycoform-resolved unfolding approach based on a high-throughput ion mobility-mass spectrometry (IM-MS) platform. This method integrates high-throughput unfolding with parallel fragmentation, enabling simultaneous analysis of sialylation patterns, stoichiometries, and their impact on conformational stability. Applying this approach to fetuin, we identified distinct sialylation patterns and their differential influence on protein conformation, namely sialylation-induced stabilization during early unfolding and increased flexibility in later unfolding stages. IM-MS-guided molecular dynamics simulations revealed that increased sialylation enhances the initial conformational stability, likely through enhanced electrostatic interactions and hydrogen bonding. These findings highlight the complex interplay between sialylation and protein dynamics and establish glycoform-resolved unfolding IM-MS as a powerful tool for characterizing glycoprotein conformational landscapes.

Pain, obesity, adenosine salvage disruption, and smoking behavior mediate the effect of gut microbiota on sleep disorders: results from network Mendelian randomization and 16S rDNA sequencing.

Objectives: The objective of this study is to investigate the indirect causalities between gut microbiota and sleep disorders. Methods: In stage 1, we utilized 196 gut microbiota as the exposure factor and conducted a two-sample univariable Mendelian randomization (MR) analysis on five sleep disorders: insomnia, excessive daytime sleepiness (EDS), sleep-wake rhythm disorders (SWRD), obstructive sleep apnea (OSA), and isolated REM sleep behavior disorder (iRBD). In stage 2, we validated the MR findings by comparing fecal microbiota abundance between patients and healthy controls through 16S rDNA sequencing. In stage 3, we explored the indirect pathways by which the microbiota affects sleep, using 205 gut microbiota metabolic pathways and 9 common risk factors for sleep disorders as candidate mediators in a network MR analysis. Results: In stage 1, the univariable MR analysis identified 14 microbiota potentially influencing five different sleep disorders. In stage 2, the results from our observational study validated four of these associations. In stage 3, the network MR analysis revealed that the Negativicutes class and Selenomonadales order might worsen insomnia by increasing pain [mediation: 12.43% (95% CI: 0.47, 24.39%)]. Oxalobacter could raise EDS by disrupting adenosine reuptake [25.39% (1.84, 48.95%)]. Allisonella may elevate OSA risk via obesity promotion [36.88% (17.23, 56.54%)], while the Eubacterium xylanophilum group may lower OSA risk by decreasing smoking behavior [7.70% (0.66, 14.74%)]. Conclusion: Triangulation of evidence from the MR and observational study revealed indirect causal relationships between the microbiota and sleep disorders, offering fresh perspectives on how gut microbiota modulate sleep.

Legionella maintains host cell ubiquitin homeostasis by effectors with unique catalytic mechanisms.

The intracellular bacterial pathogen Legionella pneumophila modulates host cell functions by secreting multiple effectors with diverse biochemical activities. In particular, effectors of the SidE family interfere with host protein ubiquitination in a process that involves production of phosphoribosyl ubiquitin (PR-Ub). Here, we show that effector LnaB converts PR-Ub into ADP-ribosylated ubiquitin, which is further processed to ADP-ribose and functional ubiquitin by the (ADP-ribosyl)hydrolase MavL, thus maintaining ubiquitin homeostasis in infected cells. Upon being activated by actin, LnaB also undergoes self-AMPylation on tyrosine residues. The activity of LnaB requires a motif consisting of Ser, His and Glu (SHxxxE) present in a large family of toxins from diverse bacterial pathogens. Thus, our study sheds light on the mechanisms by which a pathogen maintains ubiquitin homeostasis and identifies a family of enzymes capable of protein AMPylation.

The evolutionary game of establishing a remote consultation system based on the downward allocation of medical resources in a medical alliance.

As a crucial component of hierarchical diagnosis and treatment systems, medical alliances in China are responsible for promoting the downward allocation of high-quality medical resources. Remote consultation, as an essential means to achieve this goal, is of practical importance in the realization of resource sharing between hospitals within medical alliances in China. The existing research on the construction of remote consultations within medical alliances has achieved fruitful results in both theory and practice. However, the establishment of remote consultation involves many factors, and the current research mainly focuses on the influence of traditional economic profit and loss on the construction of remote consultation. In view of the practical problems existing in the operation of medical and health services in China, such as the need to improve the capacity of primary medical and health services and the poor sinking effect of high-quality medical resources, it is of great importance to systematically study the promotion strategy of the construction of remote consultation within the medical alliance to build a reasonable order of medical treatment. Therefore, by determining the logical path formed by the remote consultation channel and on the basis of traditional profit and loss parameters, this paper fully considers the relevant influence of the resource sinking utility caused by the remote consultation channel. The stability of the evolutionary system is analyzed, and a numerical simulation is used to explore the impact of key parameters on system evolution. The research results indicate that the establishment of a remote consultation system between hospitals at different levels is primarily influenced by factors such as the initial proportion of the establishment strategy chosen by both parties, the establishment cost, the distribution proportion of the government subsidy, the distribution proportion of the economic benefit, and the effectiveness proportion in the utility derived from the downward allocation of resources and reputational damage. The findings suggest that moderate to high levels of reputation loss do not significantly influence the final decision-making process for either party. Government subsidies can have an impact on hospital decision-making in the early stages, and in the long term, the resource sinking utility is more appealing than the economic benefits. To a certain extent, this study enriches the related research on remote consultation and the sinking of high-quality medical resources, provides reliable theoretical and method support for the sinking of high-quality medical resources, promotes the construction of remote consultation in medical alliances in China, and provides a decision-making reference and basis for the government and health administrative departments to formulate relevant policies.