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AIM: To review and summarize the mechanism hypothesis, influencing factors and possible consequences of macular retinal displacement after idiopathic macular hole (IMH) surgery. METHODS: PubMed and Web of Science database was searched for studies published before April 2023 on “Retinal displacement”, “Idiopathic macular holes”, and “Macular displacement”. RESULTS: Recently, more academics have begun to focus on retinal displacement following idiopathic macular holes. They found that internal limiting membrane (ILM) peeling was the main cause of inducing postoperative position shift in the macular region. Moreover, several studies have revealed that the macular hole itself, as well as ILM peeling method, will have an impact on the result. In addition, this phenomenon is related to postoperative changes in macular retinal thickness, cone outer segment tips line recovery, the occurrence of dissociated optic nerve fiber layer (DONFL) and the degree of metamorphopsia. CONCLUSION: As a subclinical phenomenon, the clinical significance of postoperative macular displacement cannot be underestimated as it may affect the recovery of anatomy and function.

Abstract Background Adult neurogenesis occurs in the subventricular zone (SVZ) and the subgranular zone of the dentate gyrus in the hippocampus. The neuronal stem cells in these two neurogenic niches respond differently to various physiological and pathological stimuli. Recently, we have found that the decrement of carboxypeptidase E (CPE) with aging impairs the maturation of brain-derived neurotrophic factor (BDNF) and neurogenesis in the SVZ. However, it remains unknown whether these events occur in the hippocampus, and what the role of CPE is in the adult hippocampal neurogenesis in the context of Alzheimer’s disease (AD). Methods In vivo screening was performed to search for miRNA mimics capable of upregulating CPE expression and promoting neurogenesis in both neurogenic niches. Among these, two agomirs were further assessed for their effects on hippocampal neurogenesis in the context of AD. We also explored whether these two agomirs could ameliorate behavioral symptoms and AD pathology in mice, using direct intracerebroventricular injection or by non-invasive intranasal instillation. Results Restoration of CPE expression in the hippocampus improved BDNF maturation and boosted adult hippocampal neurogenesis. By screening the miRNA mimics targeting the 5’UTR region of Cpe gene, we developed two agomirs that were capable of upregulating CPE expression. The two agomirs significantly rescued adult neurogenesis and cognition, showing multiple beneficial effects against the AD-associated pathologies in APP/PS1 mice. Of note, noninvasive approach via intranasal delivery of these agomirs improved the behavioral and neurocognitive functions of APP/PS1 mice. Conclusions CPE may regulate adult hippocampal neurogenesis via the CPE–BDNF–TrkB signaling pathway. This study supports the prospect of developing miRNA agomirs targeting CPE as biopharmaceuticals to counteract aging- and disease-related neurological decline in human brains.

Cognitive dysfunction is a core symptom common in psychiatric disorders including depression that is primarily managed by antidepressants lacking efficacy in improving cognition. In this study, we report a novel dual serotonin transporter and voltage-gated potassium Kv7/KCNQ/M-channel inhibitor D01 (a 2-methyl-3-aryloxy-3-heteroarylpropylamines derivative) that exhibits both anti-depression effects and improvements in cognition. D01 inhibits serotonin transporters (Ki = 30.1 ± 6.9 nmol/L) and M channels (IC50 = 10.1 ± 2.4 μmol/L). D01 also reduces the immobility duration in the mouse FST and TST assays in a dose-dependent manner without a stimulatory effect on locomotion. Intragastric administrations of D01 (20 and 40 mg/kg) can significantly shorten the immobility time in a mouse model of chronic restraint stress (CRS)-induced depression-like behavior. Additionally, D01 dose-dependently improves the cognitive deficit induced by CRS in Morris water maze test and increases the exploration time with novel objects in normal or scopolamine-induced cognitive deficits in mice, but not fluoxetine. Furthermore, D01 reverses the long-term potentiation (LTP) inhibition induced by scopolamine. Taken together, our findings demonstrate that D01, a dual-target serotonin reuptake and M channel inhibitor, is highly effective in the treatment-resistant depression and cognitive deficits, thus holding potential for development as therapy of depression with cognitive deficits.

BackgroundThere is a consensus that both nonsuicidal self-injury (NSSI) and suicidal ideation as risk factors for suicidal behavior have a strong connection. However, a lack of longitudinal information has limited the clarification of the concrete relationship between them.AimsThis study aimed to examine the specific mechanism between NSSI and suicidal ideation over time, during adolescence.MethodA longitudinal study was conducted with 193 Chinese adolescents. NSSI and suicidal ideations were examined over the course of a 1year followed-up, and three waves of data were collected.ResultsThe NSSI at time T1 significantly positively predicted suicidal ideation at time T2; Suicidal ideation at time T2 also significantly positively predicted NSSI at time T3.LimitationsGiven that the small number of participants with suicidal ideation and NSSI, the findings of the study should be interpreted with caution and a lager sample is needed in the future.ConclusionIt was suggested that NSSI may occur before suicidal ideation, which in turn would strengthen NSSI, so interventions should be carried out from two aspects (behaviors and thoughts) to improve adolescents’ mental health.

AIM: To observe the effects of N-acetylserotonin (NAS) administration on retinal ischemia-reperfusion (RIR) injury in rats and explore the underlying mechanisms involving the high mobility group box 1 (HMGB1)/receptor for advanced glycation end-products (RAGE)/nuclear factor-kappa B (NF-κB) signaling pathway. METHODS: A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye. Eighty male Sprague Dawley were randomly divided into five groups: sham group (n=8), RIR group (n=28), RIR+NAS group (n=28), RIR+FPS-ZM1 group (n=8) and RIR+NAS+ FPS-ZM1 group (n=8). The therapeutic effects of NAS were examined by hematoxylin-eosin (H&E) staining, and retinal ganglion cells (RGCs) counting. The expression of interleukin 1 beta (IL-1β), HMGB1, RAGE, and nod-like receptor 3 (NLRP3) proteins and the phosphorylation of nuclear factor-kappa B (p-NF-κB) were analyzed by immunohistochemistry staining and Western blot analysis. The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats. With NAS therapy, the HMGB1 and RAGE expression decreased significantly, and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression. Additionally, NAS exhibited an anti-inflammatory effect by reducing IL-1β expression. The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression, so as to the IL-1β expression and retinal edema, accompanied by an increase of RGCs in RIR rats. CONCLUSION: NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway, which may be a useful therapeutic target for retinal disease.

With the rapid development of economic globalization and information technology, the projects undertaken by enterprises are gradually becoming larger and more complex. The multi-project management model has become the norm in enterprise management, and it shows a trend of decentralization in terms of geographical distribution and management environment. This decentralization mainly manifests in the fact that each project has its own private information and benefit objectives and shares limited global resources with other projects during the execution process, forming a decentralized decision-making environment. As an extension of the resource-constrained project scheduling problem, the decentralized resource-constrained multi-project scheduling problem integrates single-project scheduling and global resource coordination allocation in a decentralized decision-making environment with multiple independent decision-makers. Furthermore, when considering global resources as multi-skilled staff, the decentralized multi-project scheduling problem sharing multi-skilled staff studied in this paper is proposed. A two-layer model containing local scheduling and global coordination decision-making is established to describe this problem. A two-layer approach (TLA) is proposed to solve this problem. In the local scheduling layer, a bat algorithm based on forward-backward scheduling (BAFBS) is developed to generate local baseline schedules to minimize the single-project completion time. In the global coordination decision-making layer, a variable neighborhood tabu search algorithm with greedy assignment strategy is designed to resolve global resource conflicts to minimize the multi-project total tardiness cost. Computational experiments are conducted based on the Multi-Project Scheduling Problem LIBrary dataset. The results show that the BAFBS can obtain high-quality local baseline schedules. Compared to the existing decentralized and centralized methods, our proposed TLA can get better solutions on most problem subsets, which proves that our approach can effectively coordinate the allocation of multi-skilled staff among multiple projects.

Abstract As a newly identified checkpoint, T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is highly expressed on CD4+ T cells, CD8+ T cells, natural killer (NK) cells, regulatory T cells (Tregs), and tumor-infiltrating lymphocytes (TILs). TIGIT has been associated with NK cell exhaustion in vivo and in individuals with various cancers. It not only modulates NK cell survival but also mediates T cell exhaustion. As the primary ligand of TIGIT in humans, CD155 may be the main target for immunotherapy due to its interaction with TIGIT. It has been found that the anti-programmed cell death protein 1 (PD-1) treatment response in cancer immunotherapy is correlated with CD155 but not TIGIT. Anti-TIGIT alone and in combination with anti-PD-1 agents have been tested for cancer immunotherapy. Although two clinical studies on advanced lung cancer had positive results, the TIGIT-targeted antibody, tiragolumab, recently failed in two new trials. In this review, we highlight the current developments on TIGIT for cancer immunotherapy and discuss the characteristics and functions of TIGIT.

BackgroundSpondylitis caused by Brucella infection is a rare but challenging condition, and its successful management depends on timely diagnosis and appropriate treatment. This study reports two typical cases of thoracic and lumbar brucellosis spondylitis, highlighting the pivotal roles of real-time polymerase chain reaction (real-time PCR) detection and surgical intervention.Case presentationCase 1 involved a 49-year-old male shepherd who presented with a 6-month history of fever (40°C), severe chest and back pain, and 2-week limited lower limb movement with night-time exacerbation. Physical examination revealed tenderness and percussion pain over the T9 and T10 spinous processes, with grade 2 muscle strength in the lower limbs. CT showed bone destruction of the T9 and T10 vertebrae with narrowing of the intervertebral space, whereas MRI demonstrated abnormal signals in the T9–T10 vertebrae, a spinal canal abscess, and spinal cord compression. The Rose Bengal plate agglutination test was positive. Case 2 was a 59-year-old man who complained of severe thoracolumbar back pain with fever (39.0°C) and limited walking for 2 months. He had a 2.5 kg weight loss and a history of close contact with sheep. The Rose Bengal test was positive, and the MRI showed inflammatory changes in the L1 and L2 vertebrae. Diagnosis and treatment: real-time PCR confirmed Brucella infection in both cases. Preoperative antimicrobial therapy with doxycycline, rifampicin, and ceftazidime-sulbactam was administered for at least 2 weeks. Surgical management involved intervertebral foraminotomy-assisted debridement, decompression, internal fixation, and bone grafting under general anesthesia. Postoperative histopathological examination with HE and Gram staining further substantiated the diagnosis. Outcomes: both patients experienced significant pain relief and restored normal lower limb movement at the last follow-up (4–12 weeks) after the intervention.ConclusionReal-time PCR detection offers valuable diagnostic insights for suspected cases of brucellosis spondylitis. Surgical treatment helps in infection control, decompression of the spinal cord, and restoration of stability, constituting a necessary and effective therapeutic approach. Prompt diagnosis and comprehensive management are crucial for favorable outcomes in such cases.

Mixed matrix composite membranes (MMCMs) are considered as one of the potential directions for the development of CO2 capture membranes. Nevertheless, the high cost and the challenging nature of improving separation performance are significant obstacles that prevent MMCMs from being widely applied in practice. In this study, we developed a cost-effective modified pore-optimized MOF-808 (MOF-808@PVAm) and utilized it to fabricate high-performance CO2 capture MMCMs. Specifically, MOF-808 and polyvinylamine (PVAm) were cross-linked by γ-(2,3-epoxypropoxy) propytrimethoxysilane (KH-560), which improved the pore structure characteristics of MOF-808 and led to high-performance MMCMs. For 2 bar feed gas (CO2/N2, 15/85), the MMCM with 33.33 wt.% MOF-808@PVAm loading displayed remarkable CO2 permeance of 2753 GPU and selectivity of 181. The prepared MMCM demonstrated good operational stability in simulated flue gas and exhibited potential for application in various gas purification fields (CO2/CH4, CO2/H2) through gas permeation tests.

Diabetes serves as a severe chronic disease that severely affects the normal life of human beings. Diabetes causes the complication of diabetic wound dysfunction, which is characterized by sustained inflammation, altered angiogenesis, delayed epithelialization and abnormal secretion of protease. Dang-Gui-Bu-Xue decoction (DBD) is a Chinese traditional medicine that comprises Radix Astragali and Radix Angelicae sinensis and is widely applied in treatment of multiple diseases owing to its functions against inflammation, lipid peroxidation and oxidative stress. Nevertheless, the impact of DBD on diabetic wound healing remains elusive. In this study, we aimed to explore the function of DBD in the regulation of wound healing. We observed that the gavage administration of DBD reduced the wound area, inflammatory infiltration, inflammatory factor levesl, and enhanced granulation tissue formation, wound extracellular matrix (ECM) production, and CD31 accumulation in the diabetic rat wound model, and the co-treatment of gavage administration and the external administration of gauze containing DBD further improved the wound healing effect, while the combination of Notch signaling inhibitor DAPT ((N- [N- (3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester)) could attenuate the improvement. Regarding to the mechanism, the expression levels of Notch1, Delta-like canonical Notch ligand 4 (Dll4), Jagged1, and Hairy Enhancer of Split-1 (Hes1) were increased by DBD, while the treatment of DAPT impaired the effect in the rats. Furthermore, we found that the high glucose (HG)-inhibited viability and tube formation were induced by DBD in human umbilical vein endothelial cells (HUVECs), in which DAPT could reverse this effect. Therefore, we concluded that DBD contributed to wound healing by the activation of Notch signaling. Our finding provides new insight into the potential role of DBD in promoting diabetic wound healing.

Membrane-based separation technology exhibits significant potential in the fields of CO2 capture and gas purification. Mixed-matrix membranes (MMMs) integrate the easy processing of polymeric materials with excellent transport properties of fillers, and thereby have become a focus for the next-generation gas separation membranes. Herein, we demonstrated a novel mixed-matrix membrane comprising porous organic molecular cages (POCs) and amine-rich polyvinylamine (PVAm) polymer matrix for efficient CO2 separation. Micro-sized CC3 crystals featuring a pore size of ∼4.9 Å, a high micropore volume of 0.16 cm3 g−1 and specific surface area of 326 m2 g−1 were synthesized and immobilized onto the surface of the PVAm thin selective layer to generate rapid CO2-transport channels. The resulting CC3/PVAm/mPSf MMM displayed excellent binary gas mixture (CO2/N2 15/85 vol %) separation performance, with a high CO2 permeance of 1546 GPU, and appreciable CO2/N2 selectivity of 33 at 1.5 bar, which was superior to most reported POCs-based membranes and thin film composite membranes, accompanied with excellent long-term operational stability. The CO2-selective separation facilitated by the incorporation of POCs provided a new inspiration for the development of novel MMMs for efficient CO2 capture.

Abstract Background Discoid meniscus (DM) and femoral trochlear dysplasia (FTD) are common knee disorders. Both as congenital malformation, whether there is a connection between them is unclear and the research on their prevalence in the general population is inadequate. This study aimed to investigate the prevalence of FTD and DM in the general population through a large sample size, and to explore the relationship between them. Study design Retrospective study. Methods Patients undergoing knee magnetic resonance imaging (MRI) examinations at our outpatient clinic were screened and 1003 patients were enrolled in DM group with 989 patients in non-DM (NDM) group. The type of DM and FTD was classified with Watanabe classification and Dejour’s classification, respectively. The prevalence of FTD and DM in the general population and the relationship between them were evaluated. Results The prevalence of DM and FTD was 10.0% and 14.5%, respectively. The overall percentage of FTD was higher in DM group (P

Objective: To describe our experience of reducing anastomotic leakage, a problem that has not been properly solved. Methods: Starting in January 2020, we began implementing our integrated strategy (application of an esophageal diameter-approximated slender gastric tube, preservation of the fibrous tissue around the residual esophagus and thyroid inferior pole anastomosis) in consecutive patients undergoing esophagectomy without a nasogastric tube or a nasal-jejunum feeding tube. Additionally, the blood supply at the site of the anastomosis was evaluated with a near-infrared fluorescence thoracoscope after the completion of esophagogastric anastomosis in the integrated strategy group. Results: Of 570 patients who were reviewed, 119 (20.9%) underwent the integrated strategy, and 451 (79.1%) underwent the conventional strategy. The rate of anastomotic leakage was 2.5% in the integrated strategy group and 10.2% in the conventional strategy group (p = 0.008). In the integrated strategy group, the site of most of the anastomotic blood supply was the residual esophagus dominant (82.4%), followed by the gastroesophageal dual-dominant (12.6%) and the gastric tube dominant (5.0%). The reconstruction route was more likely to be orthotopic in the integrated strategy group than in the conventional strategy group (89.9% vs. 38.6%, p = 0.004). Gastric dilation was identified in 3.4% of the patients in the integrated strategy group and in 21.1% in the conventional strategy group. Conclusions: Patients who underwent our proposed integrated strategy (Zhengzhou Strategy) during McKeown esophagectomy without a nasogastric tube or a nasal-jejunum feeding tube had a strikingly lower rate of anastomotic leakage and a relatively lower rate of postoperative complications, such as gastric tube dilation and delayed gastric emptying.

Docetaxel (Doc) plays a crucial role in clinical antineoplastic practice. However, it is continuously documented that tumors frequently develop chemoresistance and relapse, which may be related to polyploid giant cancer cells (PGCCs). The aim of this study was investigate the formation mechanism and biological behavior of PGCCs induced by Doc. Ovarian cancer cells were treated with Doc, and then the effect of Doc on cellular viability was evaluated by MTT assay and microscopic imaging analysis. The biological properties of PGCCs were further evaluated by Hoechst 33342 staining, cell cycle and DNA content assay, DNA damage response (DDR) signaling detection, β-galactosidase staining, mitochondrial membrane potential detection, and reverse transcription-quantitative polymerase chain reaction. The results indicated that Doc reduced cellular viability; however, many cells were still alive, and were giant and polyploid. Doc increased the proportion of cells stayed in the G2/M phase and reduced the number of cells. In addition, the expression of γ-H2A.X was constantly increased after Doc treatment. PGCCs showed senescence-associated β-galactosidase activity and an increase in the monomeric form of JC-1. The mRNA level of octamer-binding transcription factor 4 (OCT4) and krüppel-like factor 4 (KLF4) was significantly increased in PGCCs. Taken together, our results suggest that Doc induces G2/M cell cycle arrest, inhibits the proliferation and activates persistent DDR signaling to promote the formation of PGCCs. Importantly, PGCCs exhibit a senescence phenotype and express stem cell markers.

With the rapid development of the transportation industry, permeable asphalt pavement has become widely used in the construction of expressways and urban roads due to its safety, comfort, and environmental protection characteristics. However, water-temperature coupling can damage the mechanical properties of permeable asphalt mixtures. The use of high-viscosity modified asphalt can improve the water damage resistance of the mixture to a certain extent, resulting in better mechanical properties. This paper focuses on the preparation of PAC-13 mixture specimens using high-viscosity modified asphalt and the study of its noise reduction and anti-skidding properties under water-temperature coupling. SMA-13 and AC-13 are used for comparative research. The influence of water-temperature coupling on the functional characteristics of permeable asphalt mixture is analyzed through standing wave tube test and pendulum test. The results show that PAC-13 exhibits better noise reduction and anti-skidding characteristics than SMA-13 and AC-13. As the temperature increases, the skid resistance of asphalt mixtures weakens, but the noise reduction properties are less affected. Furthermore, the noise reduction and anti-skidding properties of the three mixtures are significantly damaged by the action of water, with PAC-13 being the most affected. Nevertheless, PAC-13 still exhibits the best noise reduction and anti-skidding properties.

IntroductionRecent studies have found that the sound-induced alleviation of visual attentional blink, a well-known phenomenon exemplifying the beneficial influence of multisensory integration on time-based attention, was larger when that sound was semantically congruent relative to incongruent with the second visual target (T2). Although such an audiovisual congruency effect has been attributed mainly to the semantic conflict carried by the incongruent sound restraining that sound from facilitating T2 processing, it is still unclear whether the integrated semantic information carried by the congruent sound benefits T2 processing.MethodsTo dissociate the congruence-induced benefit and incongruence-induced reduction in the alleviation of visual attentional blink at the behavioral and neural levels, the present study combined behavioral measures and event-related potential (ERP) recordings in a visual attentional blink task wherein the T2-accompanying sound, when delivered, could be semantically neutral in addition to congruent or incongruent with respect to T2.ResultsThe behavioral data clearly showed that compared to the neutral sound, the congruent sound improved T2 discrimination during the blink to a higher degree while the incongruent sound improved it to a lesser degree. The T2-locked ERP data revealed that the early occipital cross-modal N195 component (192–228 ms after T2 onset) was uniquely larger in the congruent-sound condition than in the neutral-sound and incongruent-sound conditions, whereas the late parietal cross-modal N440 component (400–500 ms) was prominent only in the incongruent-sound condition.DiscussionThese findings provide strong evidence that the modulating effect of audiovisual semantic congruency on the sound-induced alleviation of visual attentional blink contains not only a late incongruence-induced cost but also an early congruence-induced benefit, thereby demonstrating for the first time an unequivocal congruent-sound-induced benefit in alleviating the limitation of time-based visual attention.

The prevalence of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) has emerged as a major public health concern in China. When patients with HIV infection undergo surgical treatment, there are two main challenges. Firstly, medical staff face a high risk of HIV infection due to occupational exposure. Secondly, the patient’s immune function is impaired, increasing the risk of opportunistic infections and postoperative complications. The surgical treatment of such patients is unique, and the risk of occupational exposure during the operation primarily depends upon the viral load of HIV/AIDS patients. Therefore, perioperative antiretroviral therapy is of paramount importance in order to standardize the perioperative antiretroviral therapy (ART) for HIV/AIDS patients. The Surgery Group of the Chinese Association of STD and AIDS Prevention and Control, in collaboration with the Treatment Association, and Surgery Group of the Chinese Medical Association of Tropical Diseases and Parasitology, has developed an expert consensus on perioperative antiretroviral therapy for HIV/AIDS patients. This consensus encompasses various aspects, including surgical risk assessment, selection of perioperative antiretroviral therapy regimens, prevention of opportunistic infections, and the crucial focus on rapid preoperative viral load reduction and immune function reconstruction for HIV/AIDS patients.

Rapid diagnosis of urogenital schistosomiasis caused by Schistosoma haematobium requires an accurate and timely assay, especially for low-intensity S. haematobium infection cases and in non-endemic areas. The mitochondrial cytochrome c oxidase 1 (cox1) gene fragment of S. haematobium was selected as detection target as this short fragment, which can be rapidly sequenced and yet possess good diagnostic resolution. A pair of primers and a fluorescent probe were designed according to the principle of recombinase-aided amplification (RAA), which was subsequently optimized and applied as an S. haematobium-specific RAA assay. Its diagnostic performance was validated for sensitivity and specificity in comparison to microscopy-based egg counting after urine filtration. The RAA assay could detect as little as 10 copies/μL of S. haematobium recombinant plasmid, and no cross-reactions were observed with S. mansoni, S. japonicum, Ancylostoma duodenale, Clonorchis sinensis, Echinococcus granulosus, or Ascaris lumbricoides. This test can be conducted at 39 °C and the whole RAA reaction can be completed within 20 min. The validation of the RAA assay showed that it had 100 % consistency with urine-egg microscopy, as it does not require an elaborate reading tool, is simple to use, and should be useful for field diagnostics and point-of-care applications.

Present-day Li+ storage materials generally suffer from sluggish low-temperature electrochemical kinetics and poor high-temperature cycling stability. Herein, based on a Ca2+ substituted Mg2Nb34O87 anode material, we demonstrate that decreasing the ionic packing factor is a two-fold strategy to enhance the low-temperature electrochemical kinetics and high-temperature cyclic stability. The resulting Mg1.5Ca0.5Nb34O87 shows the smallest ionic packing factor among Wadsley–Roth niobate materials. Compared with Mg2Nb34O87, Mg1.5Ca0.5Nb34O87 delivers a 1.6 times faster Li​+ ​diffusivity at −20 ​°C, leading to 56% larger reversible capacity and 1.5 times higher rate capability. Furthermore, Mg1.5Ca0.5Nb34O87 exhibits an 11% smaller maximum unit-cell volume expansion upon lithiation at 60 ​°C, resulting in better cyclic stability; at 10C after 500 cycles, it has a 7.1% higher capacity retention, and its reversible capacity at 10C is 57% larger. Therefore, Mg1.5Ca0.5Nb34O87 is an all-climate anode material capable of working at harsh temperatures, even when its particle sizes are in the order of micrometers.

Under a certain temperature, cracks in asphalt mixtures can heal themselves, but water in the cracks will reduce the self-healing performance of the asphalt mixture. In this study, surfactants were added to asphalt mixtures. In the presence of water, the characteristics of amphiphilic surfactants are used to promote the adsorption between asphalt and aggregates; In this paper, the ability of surfactants to promote the formation of adsorption of asphalt on the crystal surface is verified using a combination of molecular simulations and macroscopic experiments. Molecular simulation results show that the adsorption energies of asphalt and surfactants, surfactants and silica, and asphalt and silica are all negative. Adsorption can occur between the three interfaces, and the surfactants effectively pulls the asphalt molecules onto the silica molecules, achieving adsorption similar to that between asphalt organic polymers and crystals. Macroscopic experiments show that in asphalt mixtures with active agents added, the active agent can be adsorbed on the surface of the aggregate, part of the asphalt is adsorbed on the surface of the active agent, and part is directly adsorbed on the gravel. Some asphalt is also adsorbed on the aggregate under the action of pure water, but the total adsorption capacity is lower than that of asphalt mixtures containing surfactants.

Abstract Docetaxel (Doc) is a cornerstone of chemotherapy; however, treatment with Doc often and inevitably leads to drug resistance and the formation of polyploid giant cancer cells (PGCCs). In this study, we investigated the effect of Doc on non-small cell lung cancer to explore the role of PGCCs in drug resistance and the molecular mechanisms that regulate this resistance. We found that Doc induced G2/M cell cycle arrest and cell death in A549 and NCI-H1299 cells. However, many cells remained alive and became PGCCs by decreasing the expression of key regulatory proteins related to the cell cycle and proliferation. Notably, the PGCCs showed typical features of senescence, especially upregulation of p21 and p-histone H2A.X expression. Moreover, the mRNA level of IL-1β in the senescence-associated secretory phenotype was increased significantly with the development of PGCCs. Inhibition of IL-1β reduced the expression of p-histone H2A.X and promoted polyploidy to enhance the proapoptotic effect of Doc. Taken together, our results suggested that IL-1β was involved in the formation of PGCCs and regulated the senescence of PGCCs, which contributed to drug resistance to Doc. Therefore, targeting IL-1β in PGCCs may be a novel approach to overcome drug resistance.

Abstract The ever‐growing open‐source software tools in different domains increase the difficulty of software selection from the end‐users perspective. The process of evaluating, comparing, and selecting open‐source solutions is far from trivial. Especially, when additional requirements need to be considered, the existing methodologies will fail to adapt to the new tasks. The objective of this study is to present a solution for dealing with this issue. A novel approach, CTHP, is presented for the evaluation and selection of open‐source software in the Bioinformatics domain. First, the ISO 25010 quality model is chosen as the basis. This model is customised according to the special characteristics of the Bioinformatics applications. The customisation is done by extracting the quality factors from the Bioinformatics applications, weighting these factors from the viewpoints of both developers and end‐users, and adding them to the model. After that, Three‐way Decision and Delphi Hierarchy Process are integrated to assist in the selection for adoption. Finally, as a case study, the proposed approach is applied to assist the decision‐making process of two popular natural language processing frameworks in the Bioinformatics area. Our study is a valuable contribution since it provides a systematic way to document the decision‐making process and help the researchers and practitioners of Bioinformatics to make better decisions among the alternatives.

Abstract Background Maintaining homeostasis of Ca2+ stores in the endoplasmic reticulum (ER) is crucial for proper Ca2+ signaling and key cellular functions. Although Ca2+ depletion has been known to cause ER stress which in turn activates the unfolded protein response (UPR), how UPR sensors/transducers respond to excess Ca2+ when ER stores are overloaded remain largely unclear. Results Here, we report for the first time that overloading of ER Ca2+ can directly sensitize the IRE1α-XBP1 axis. The overloaded ER Ca2+ in TMCO1-deficient cells can cause BiP dissociation from IRE1α, promote the dimerization and stability of the IRE1α protein, and boost IRE1α activation. Intriguingly, attenuation of the over-activated IRE1α-XBP1s signaling by a IRE1α inhibitor can cause a significant cell death in TMCO1-deficient cells. Conclusions Our data establish a causal link between excess Ca2+ in ER stores and the selective activation of IRE1α-XBP1 axis, underscoring an unexpected role of overload of ER Ca2+ in IRE1α activation and in preventing cell death.

Background: Navigation assistance is very important for users when roaming in virtual reality scenes, however, the traditional navigation method requires users to manually request a map for viewing, which leads to low immersion and poor user experience. Methods: To address this issue, first, we collected data when users need navigation assistance in a virtual reality environment, including various eye movement features such as gaze fixation, pupil size, and gaze angle, etc. After that, we used the Boostingbased XGBoost algorithm to train a prediction model, and finally used it to predict whether users need navigation assistance in a roaming task. Results: After evaluating the performance of the model, the accuracy, precision, recall, and F1-score of our model reached about 95%. In addition, by applying the model to a virtual reality scene, an adaptive navigation assistance system based on the user’s real-time eye movement data was implemented. Conclusions: Compared with traditional navigation assistance methods, our new adaptive navigation assistance could enable the user to be more immersive and effective during roaming in VR environment.

Abstract Background The predominant cancer-related deaths worldwide are caused by lung cancer, particularly non-small cell lung cancer (NSCLC), despite the fact that numerous therapeutic initiatives have been devised to improve the outcomes. Ankyrin repeat domain (ANKRD) is one of the widespread protein structural motifs in eukaryotes but the functions of ANKRD proteins in NSCLC progression remains unclear. Methods We performed integrative bioinformatical analysis to determine the dysregulated expression of ANKRDs in multiple tumors and the association between ANKRD29 expression and the NSCLC tumor environment. Quantitative real-time PCR (qRT-PCR), western blot, immunohistochemistry (IHC), and tissue microarray (TMA) assays were used to investigate the expression of ANKRD29 in NSCLC cell lines. The role of ANKRD29 in NSCLC cell proliferation and migration in vitro was deteceted by 5-bromodeoxyuridine (BrdU) incorporation, colony formation, flow cytometry, would-healing, trans-well, and western blot experiment. RNA-seq technology was applied to deciper the molecular mechanism regulated by ANKRD29 in NSCLC. Results We constructed a valuable risk-score system for predicting the overall survival outcomes of NSCLC patients based on the expression of five hub ANKRD genes. And we found that the hub gene ANKRD29 was remarkedly decreased in NSCLC tissues and cell lines due to the promoter hypermethylation, and revealed that high ANKRD29 expression obviously correlated with patients’ better clinical outcome. Overexpression of ANKRD29 significantly inhibited cell proliferation and migration, promoted the cancerous cells’ sensitivity to carboplatin and enhanced the killing ability of T cells in NSCLC cells. Interestingly, ANKRD29 can be served as a biomarker to predict the response to immunotherapy in NSCLC. Mechanically, RNA-seq results showed that ANKRD29 could regulate MAPK signaling pathway. Moreover, we screened two potential agonists for ANKRD29. Conclusions ANKRD29 functions as a new tumor suppressor in NSCLC tumorigenesis and could be developed as a biomarker for prognostic prediction, immunotherapy response, and drug susceptibility evaluation of NSCLC in the future.

This study aimed to investigate the impact of various vasculopathies alongside left ventricular hypertrophy (LVH) on cardiovascular risk in the elderly. This prospective cohort study included 3339 older adults from the Northern Shanghai Study, classified into four mutually exclusive left ventricular (LV) geometry groups based on echocardiographic data: normal geometry, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. Vasculopathy was categorized into three primary types: arteriosclerosis, atherosclerosis, and renal senescence. Major adverse cardiovascular events (MACEs) were defined as non-fatal acute myocardial infarction, non-fatal stroke, and cardiovascular deaths according to ICD-10 codes. Over a median follow-up period of 5.7 years, 221 incident cases of MACEs were identified. Concentric hypertrophy exhibited the highest prevalence of hypertension, the most significant increase in vascular stiffness, and the highest rate of MACEs. The adjusted Cox regression analysis showed that eccentric hypertrophy is associated with an increased risk of MACEs (HR: 1.638 [95% CI: 1.151–2.331], p = 0.006), while concentric hypertrophy shows an even higher risk (HR: 1.751 [95% CI: 1.127–2.721], p = 0.013). Conversely, concentric remodeling was not significantly associated with an increased risk of MACEs. Renal senescence presents a moderate but significant risk for MACEs, with an HR of 1.361 (95% CI: 1.019–1.819; p = 0.037) when adjusted for LVH. The Kaplan–Meier analysis showed that patients with LVH and multiple vasculopathies experience the most significant decrease in survival probability (log-rank p < 0.001). The subgroup analysis revealed that LVH significantly raises the risk of MACEs, especially in older males with hypertension, diabetes, or vasculopathy. This study reinforces the importance of LVH as a predictor of adverse cardiovascular outcomes and underscores the compounded risk associated with the presence of multiple vasculopathies. Additionally, it highlights renal senescence as a distinct and independent risk factor for MACEs, separate from LVH.

Leakage is a high-incidence disease of embankment dams, and efficiently addressing this disease guarantees the safe operation of dams. Underwater leakage self-priming plugging technology is a new technology that utilizes the melting and solidifying characteristics of phase-change materials and the negative pressure in the leakage entry area to accurately plug the leakage. However, little is yet known about the underwater melting process of phase-change materials and how their characteristics influence the plugging effect. In this study, three kinds of phase-change materials, namely, paraffin, rosin, and stearic acid, were used to conduct underwater leakage self-priming plugging tests, observe and analyze the underwater melting process, and compare the plugging effects. The results showed that the underwater melting process of phase-change materials exhibited different plugging window periods depending on their melting points, specific heat capacities, and mobilities, which were the main factors affecting their plugging effects. In the final plugging stage, paraffin had the best plugging effect, but the material strength was low; rosin had good plugging compactness, but the fluidity performance was poor, and the material effective utilization was low; stearic acid had a low melting point but dispersed easily. Therefore, a blocking material with a suitable blocking window period can be produced by adjusting the material properties accordingly for an improved blocking effect.

In the field of highway construction, the application of styrene–butadiene rubber (SBR)-modified asphalt has gained popularity across different levels of road surfaces. A crucial aspect in ensuring the efficacy of this modification lies in the compatibility between SBR and the matrix asphalt. To address this, the current study utilizes molecular dynamics simulation as a technique. By establishing a model for the SBR-modified asphalt mixture, the research quantifies the compatibility level between the SBR modifier and the asphalt. The aim is to uncover the underlying mechanisms of compatibility between the SBR modifier and the base asphalt, ultimately contributing to the improvement of the storage stability of SBR-modified asphalt, which holds significant importance. The investigation began with the creation of models for both the base asphalt and the SBR modifier. A model for the SBR-modified asphalt blending system was then formulated based on these initial models. After undergoing geometry optimization and annealing procedures, the model attained its lowest energy state, providing a reliable basis for examining the performance of SBR-modified asphalt. The study proceeded to calculate solubility parameters and interaction energies of the system to evaluate the compatibility between the SBR modifier and the base asphalt at various temperatures. The analysis of these parameters shed light on the compatibility mechanism between the two components. Notably, it was found that at a temperature of 160 ℃, the compatibility was significantly enhanced. The findings were further corroborated through scanning electron microscope and rheological tests. The outcomes of this research offer theoretical guidance for the application of SBR-modified asphalt.

The outstanding thermoelectric material, SnSe, is also known for its inferior mechanical properties, which bring great inconvenience for its application in thermoelectric devices. In this work, SnSe bulks were prepared via a sequential procedure of high-pressure synthesis (HPS), ball milling, and spark plasma sintering (SPS). The produced polycrystalline samples with a unique microstructure of tightly-bound quasi-equiaxed grains exhibited excellent mechanical properties. The Vickers hardness (HV), compressive strength (σc), and bending strength (σb) reached 1.1 GPa, 300 MPa, and 90 MPa, respectively, all of which are far superior to those of ordinary polycrystalline SnSe. Furthermore, the microstructures did not deteriorate thermoelectric performance. This work demonstrated an effective procedure to prepare polycrystalline microstructure-engineered SnSe materials, which not only show advantages in device applications but also shed light on property enhancement for other layer-structured thermoelectric materials.