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Background: Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2 , a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression., Methods: Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2 -associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC., Results: NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro . NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models., Conclusions: Collectively, NUF2 -mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

White tea stored for various times have different flavors. However, the mechanism of flavor conversion remains elusive. Flavonoids and amino acids are two typical flavor components in tea. Herein, the contents of 46 flavonoids and 40 amino acids were measured in white tea (Shoumei) stored for 1, 3, 5 and 7 years, respectively. L-tryptophan, L-ornithine and L-theanine contribute to the refreshing taste of Shoumei 1 and 3. Quercetin, rutin and hesperidin contribute to aging charm and grain aroma of Shoumei 5 and 7. 306 bacterial OTUs and 268 fungal OTUs core microbiota existed in all samples. Interestingly, white teas contained higher richness of fungi than bacteria. The correlation analysis showed that the cooperation with bacteria and fungi may result in the flavonoids and amino acids composition changes in white teas during storage. Overall, this study provides new insights into flavor conversion of white tea during storage., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

High Throughput Screening is crucial in pharmaceutical companies for efficient testing in drug discovery and development. Our Vaccines Analytical Research and Development (V-AR&D) department extensively uses robotic liquid handlers in their High Throughput Analytics (HTA) group for assay development and sample screening. However, these instruments are expensive and require extensive training. Opentrons' OT-2 liquid handler offers a more affordable option (<∼ $10,000) with Python programming language and open-source flexibility, reducing training requirements. OT-2 allows broadening of testing capabilities and method transfer without significant capital investments. Two biochemical assays were conducted to assess OT-2's performance, and it demonstrated accurate pipetting with low covariance compared to Tecan EVO liquid handlers. Though OT-2 has some limitations such as lack of a crash detection system and limited deck space, it is a cost-effective, medium-throughput, and accurate liquid handling tool suitable for early-stage development and method transfer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The effect of bolt support in mining roadways with fractured or weak surrounding rock is poor, and the roof easily loses stability. Studying the support control technology of bolts on fractured surrounding rock is necessary. Based on the theories of pressure arches and combined arch support, the bolt anchorage and anchorage effect angle are proposed a model is established, and the optimal bolt anchorage is calculated. The influence of related factors on the bolt anchorage and the scope of bolt action are analysed via numerical simulation and experimental methods. The pretightening force of the bolts and the spacing between the rows of bolts are positively correlated and negatively correlated with the bolt anchorage, respectively. The compression zone conforms to the reinforced arch state when the bolt end is anchored. The experimental work shows that the maximum spacing a of the anchor rods and the length L of the anchor rods in the surrounding rock satisfy 4.28a < 2L < 5a. The support of fractured surrounding rock is discussed, and the concept of roof fall prevention and control with an increasing or constant pretightening force, high surface strength and reasonable support density as the core principles is proposed. A field test of the Youzhong Coal Mine shows that the corresponding support effect is good and that this work provides a new method for roof support of fractured surrounding rock., (© 2024. The Author(s).)

The brain is a highly adaptable organ that is molded by experience throughout life. Although the field of neuroscience has historically focused on intrinsic neuronal mechanisms of plasticity, there is growing evidence that multiple glial populations regulate the timing and extent of neuronal plasticity, particularly over the course of development. This review highlights recent discoveries on the role of glial cells in the establishment of cortical circuits and the regulation of experience-dependent neuronal plasticity during critical periods of neurodevelopment. These studies provide strong evidence that neuronal circuit maturation and plasticity are non-cell autonomous processes that require both glial-neuronal and glial-glial cross talk to proceed. We conclude by discussing open questions that will continue to guide research in this nascent field., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Purpose: The purpose of this study was to identify the temporal and spatial parameters of videofluoroscopic swallowing study (VFSS) that could predict the recovery of swallowing function in subacute stroke patients., Methods: We included 102 patients who were admitted to the Department of Rehabilitation Medicine between 2019 and 2022. Patients were classified into good and poor prognosis groups according to whether they had restored prestroke swallowing function or were able to consume sufficient nutrition via oral feeding to meet their body's needs. Univariate and multivariate regression analyses were used to identify the predictors. Calibration and discrimination were tested using the Hosmer-Lemeshow test and area under the curve (AUC), respectively., Results: Of the 102 included patients, 51 had a good prognosis for swallowing function within 6 months of onset. The final multivariate regression model included three significant factors: laryngeal closure duration (LCD) (OR: 0.998; 95% CI: 0.996-0.999; p < 0.05), maximum width of the upper esophageal sphincter opening (MWUESO) (OR: 1.251; 95% CI: 1.073-1.458; p < 0.05), and pharyngeal residual grade (PRG) (p < 0.05). The shorter LCD and larger MWUESO were positive predictors of good swallowing function outcomes, while higher PRG was a negative predictor of good outcomes. The AUC for PRG, MWUESO, and LCD were 0.767 (p < 0.05), 0.738 (p < 0.05), and 0.681 (p < 0.05), respectively., Conclusion: Identifying prognostic factors for the recovery of swallowing function in patients with poststroke dysphagia is essential for developing treatment strategies. The findings of this study may provide an important reference for developing appropriate therapeutic interventions to promote the recovery of swallowing function in stroke patients., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Background: Pulmonary hypertension is a rare, progressive disorder that can lead to right ventricular hypertrophy, right heart failure, and even sudden death. N6-methyladenosine modification and the main methyltransferase that mediates it, methyltransferase-like (METTL) 3, exert important effects on many biological and pathophysiological processes. However, the role of METTL3 in pyroptosis remains unclear., Methods and Results: Here, we characterized the role of METTL3 and the underlying cellular and molecular mechanisms of pyroptosis, which is involved in pulmonary hypertension. METTL3 was downregulated in a pulmonary hypertension mouse model and in hypoxia-exposed pulmonary artery smooth muscle cell. The small interfering RNA-induced silencing of METTL3 decreased the m6A methylation levels and promoted pulmonary artery smooth muscle cell pyroptosis, mimicking the effects of hypoxia. In contrast, overexpression of METTL3 suppressed hypoxia-induced pulmonary artery smooth muscle cell pyroptosis. Mechanistically, we identified the phosphate and tension homology deleted on chromosome 10 (PTEN) gene as a target of METTL3-mediated m6A modification, and methylated phosphate and tension homology deleted on chromosome 10 mRNA was subsequently recognized by the m6A "reader" protein insulin-like growth factor 2 mRNA-binding protein 2, which directly bound to the m6A site on phosphate and tension homology deleted on chromosome 10 mRNA and enhanced its stability., Conclusions: These results identify a new signaling pathway, the METTL3/phosphate and tension homology deleted on chromosome 10/insulin-like growth factor 2 mRNA-binding protein 2 axis, that participates in the regulation of hypoxia-induced pyroptosis.

Purpose: This study aimed to establish a population pharmacokinetic (PK) model to evaluate the dynamic relationship between the concentrations of total and unbound paclitaxel, and the exposure-response analysis of albumin-bound paclitaxel (nab-paclitaxel) after pegylated recombinant human granulocyte colony-stimulating factor (PEG-G-CSF) administration in patients with metastatic breast cancer., Methods: A total of 653 concentrations corresponding to total paclitaxel and 334 concentrations corresponding to unbound paclitaxel were analyzed in 24 subjects who randomized received a single 260 mg/m 2 dose of two nab-paclitaxel formulations with a 21-35-day washout period. PEG-G-CSF was administered to all the patients in each cycle to prevent neutropenia. The exposure-response relationships were evaluated using the exposure to total, albumin-coated, and unbound paclitaxel, as well as the reduction in neutrophil count. The exposure data were analyzed using nonlinear mixed-effect modeling. A linear regression model was used to test the statistical significance of the correlation between percentage of reduction in neutrophil count and exposure., Results: The PK characteristics of total paclitaxel were described using a three-compartment model with first-order elimination, and a mechanism-based model incorporating linear release of nab-paclitaxel and the saturated binding of unbound paclitaxel to plasma components was established. The release ratio of paclitaxel from nab-paclitaxel was estimated to be 4.60% and the maximum unbound fraction (2.76%) was reached at the end of the infusion. The study found that a longer duration of total paclitaxel concentration > 0.19 µmol/L was significantly correlated with a reduction in neutrophil count (r 2  = 0.23, P = 0.00062). Specifically, a duration of > 8.6 h was a predictor of a decreased neutrophil count., Conclusion: The decrease in neutrophils induced by nab-paclitaxel was significantly correlated with the duration above a total paclitaxel concentration of 0.19 µmol/L despite the use of PEG-G-CSF., (© 2024. Crown.)

Soft robotics promises to achieve safe and efficient interactions with the environment by exploiting its inherent compliance and designing control strategies. However, effective control for the soft robot-environment interaction has been a challenging task. The challenges arise from the nonlinearity and complexity of soft robot dynamics, especially in situations where the environment is unknown and uncertainties exist, making it difficult to establish analytical models. In this study, we propose a learning-based optimal control approach as an attempt to address these challenges, which is an optimized combination of a feedforward controller based on probabilistic model predictive control and a feedback controller based on nonparametric learning methods. The approach is purely data-driven, without prior knowledge of soft robot dynamics and environment structures, and can be easily updated online to adapt to unknown environments. A theoretical analysis of the approach is provided to ensure its stability and convergence. The proposed approach enabled a soft robotic manipulator to track target positions and forces when interacting with a manikin in different cases. Moreover, comparisons with other data-driven control methods show a better performance of our approach. Overall, this work provides a viable learning-based control approach for soft robot-environment interactions with force/position tracking capability.

To analyze the quantitative mapping relationship between the geometric errors of the five-axis CNC machine tool and the tooth surface deviation of spiral bevel gears, and identify the key geometric errors that affect the machining deviation of the spiral bevel gear tooth surface, a sensitivity analysis method for tooth surface machining deviation of spiral bevel gear based on screw theory and EFAST method is proposed. Firstly, the machining model of the spiral bevel gear tooth surface based on the five-axis CNC machine tool is established. Then, the geometric error transfer model of the machine tool is established based on the screw theory. Combined with the EFAST global sensitivity analysis method, the key geometric errors that affect tooth surface deviation are identified. Finally, the reliability and effectiveness tests are performed by comparing the results to the local sensitivity analysis method and simulating compensation for the key geometric errors. The result of compensation shows that the tooth surface deviation is reduced significantly according to global sensitivity analysis. The feasibility of applying sensitivity analysis to control the tooth surface deviation of spiral bevel gears has been demonstrated., (© 2024. The Author(s).)

Key Message: Thirteen QTLs associated with rice grain shape were localized by genome-wide association study. LOC&#95;Os01g74020, the putative candidate gene in the co-localized QTL-qGSE1.2 interval, was identified and validated. Grain shape (GS) is a key trait that affects yield and quality of rice. Identifying and analyzing GS-related genes and elucidating the physiological, biochemical and molecular mechanisms are important for rice breeding. In this study, genome-wide association studies (GWAS) were conducted based on 1, 795, 076 single-nucleotide polymorphisms (SNPs) and three GS-related traits, grain length (GL), grain width (GW) and thousand-grain weight (TGW), in a natural population which comprised 374 rice varieties. A total of 13 quantitative trait locus (QTLs) related to GL, GW and TGW were identified, respectively, of which two QTLs (qGSE1.2 and qGSE5.3) were associated with both GL and TGW. A known key GS regulatory gene, GW5, was present in the interval of qGSE5.3. Based on the qRT-PCR results, LOC&#95;Os01g74020 (OsGSE1.2) was identified as a GS candidate gene. Functional analysis of OsGSE1.2 showed that glume cell width and GW were significantly reduced, and that glume cell length, GL, TGW and single-plant yield were significantly increased in OsGSE1.2 knockout lines than those of wild type. OsGSE1.2 affects rice grain length by suppressing the elongation of glume cell and is a novel GS regulatory gene. These findings laid the foundation for molecular breeding to improve rice GS and increase rice yield and profitability., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Epsilon toxin (ETX), a potential agent of biological and toxic warfare, causes the death of many ruminants and threatens human health. It is crucial to understand the toxic mechanism of such a highly lethal and rapid course toxin. In this study, we detected the effects of ETX on the proteome and phosphoproteome of MDCK cells after 10 min and 30 min. A total of 44 differentially expressed proteins (DEPs) and 588 differentially phosphorylated proteins (DPPs) were screened in the 10 min group, while 73 DEPs and 489 DPPs were screened in the 30 min group. ETX-induced proteins and phosphorylated proteins were mainly located in the nucleus, cytoplasm, and mitochondria, and their enrichment pathways were related to transcription and translation, virus infection, and intercellular junction. Meanwhile, the protein-protein interaction network screened out several hub proteins, including SRSF1/2/6/7/11, SF3B1/2, NOP14/56, ANLN, GTPBP4, THOC2, and RRP1B. Almost all of these proteins were present in the spliceosome pathway, indicating that the spliceosome pathway is involved in ETX-induced cell death. Next, we used RNAi lentiviruses and inhibitors of several key proteins to verify whether these proteins play a critical role. The results confirmed that SRSF1, SF3B2, and THOC2 were the key proteins involved in the cytotoxic effect of ETX. In addition, we found that the common upstream kinase of these key proteins was SRPK1, and a reduction in the level of SRPK1 could also reduce ETX-induced cell death. This result was consistent with the phosphorylated proteomics analysis. In summary, our study demonstrated that ETX induces phosphorylation of SRSF1, SF3B2, THOC2, and SRPK1 proteins on the spliceosome pathway, which inhibits normal splicing of mRNA and leads to cell death.

The abnormal expression of circular RNAs (circRNAs) is emerging as a critical cause in regulation of pathological changes of hypoxic pulmonary hypertension (PH), in which ferroptosis is a new pathological change reported recently. However, how circRNAs regulate ferroptosis remains unclear. Here, we proved a significant decrease in circMyst4 expression in hypoxia. In vitro assays revealed that circMyst4 alleviated hypoxic pulmonary artery smooth muscle cell (PASMC) ferroptosis through directly combing with DDX5 in the nucleus to promote GPX4 mRNA processing and inhibiting the formation of the Eef1a1/ACSL4 complex in the cytoplasm. Additionally, superenhancer (SE) was verified to drive the generation of circMyst4. In vivo assays revealed that circMyst4 inhibited the progression of hypoxic PH. Overall, SE-driven circMyst4 may be a new potential therapeutic target for mediating PASMC ferroptosis through promoting DDX5-regulated GPX4 mRNA processing and inhibiting the binding between Eef1a1 and ACSL4., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by Elsevier Inc.)

Aim: To explore the prevalence of turnover intentions among emergency nurses across the globe, decision-makers should be offered evidence-based assistance., Background and Introduction: Compared with those of general nurses, the unique work environment and pressure significantly impact emergency nurses' turnover intention. High personnel turnover intention often hinders the provision of high-quality emergency services., Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Published and unpublished papers were identified through electronic searches of PubMed, Web of Science, EMBASE, CINAHL, and the Cochrane Library from their establishment until February 1, 2023. The literature included in this study may encompass cross-sectional studies and longitudinal studies. Two researchers independently screened the literature, extracted data, and assessed the quality of the included studies while using the tool developed by Hoy and colleagues in 2012. Stata 17.0 was used for all the statistical analyses., Results: This study included 12 articles by screening 744 articles, which included a total of 4400 nurses. All studies included in the analysis were cross-sectional. The overall prevalence of turnover intention among emergency nurses was 45%. Further analysis revealed that the turnover intention prevalence among emergency nurses in Asia was 54%, whereas in other regions, it was 38%. The turnover intention among younger nurses (61%) was significantly greater than that among older nurses (30%). Compared with the published scale, the self-developed scale resulted in a higher turnover intention rate of 52%, which was 41%., Conclusion: The prevalence of emergency nurses' turnover intention is relatively high and shows an increasing trend, with noticeable variations across different regions and age groups. Notably, Asian nurses and those younger than 35.6 years exhibit a greater intention to turnover., Patient or Public Contribution: There is no patient or public involvement, as this article is a meta-analysis., Implications for Nursing and Health Policy: Nursing managers, administrators, and policymakers must recognize the seriousness of high turnover intentions among emergency nurses and develop effective prevention strategies to address this issue globally., (© 2024. The Author(s).)

Accumulating evidence highlights p38 as a crucial factor highly activated during the process of acute kidney injury (AKI), but the application of p38 inhibitor in AKI is quite limited due to the low efficiency and poor kidney-targeting ability. Herein, a novel self-assembling peptide nanoparticle with specific p38-inhibiting activity is constructed, which linked mitogen-activated protein kinase kinase 3b (MKK3b), the functional domain of p38, with the cell-penetrating TAT sequence, ultimately self-assembling into TAT-MKK3b nanoparticles (TMNPs) through tyrosinase oxidation. Subsequent in vitro and in vivo studies demonstrated that TMNPs preferably accumulated in the renal tubular epithelial cells (RTECs) through forming protein coronas by binding to albumin, and strongly improved the reduced renal function of ischemia-reperfusion injury (IRI)-induced AKI and its transition to chronic kidney disease (CKD). Mechanically, TMNPs inhibited ferroptosis via its solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis-inducing capacity and synergistic potent antioxidant property in AKI. The findings indicated that the multifunctional TMNPs exhibited renal targeting, ROS-scavenging, and ferroptosis-mitigating capabilities, which may serve as a promising therapeutic agent for the treatment of AKI and its progression to CKD., (© 2024 Wiley‐VCH GmbH.)

Objective: This study is aimed at investigating the pharmacokinetic (PK) characteristics of pegylated liposomal mitoxantrone (PLM) in patients with relapsed/refractory lymphoma or small cell lung cancer (SCLC) by constructing population pharmacokinetic (popPK) models for both liposome-encapsulated mitoxantrone and free mitoxantrone., Methods: A total of 23 patients with relapsed/refractory lymphoma and 42 patients with SCLC were included. A popPK model was simultaneously developed utilizing a non-linear mixed effects model (NONMEM) to explore the PK profiles of liposome-encapsulated mitoxantrone and free mitoxantrone. Clearance (CL) and distribution volume (V) were calculated, and covariate analysis was employed to evaluate the influence of patient disease type, demographic information, and biochemical indicators of liver and kidney function on PK parameters., Results: The concentration-time profiles for both liposome-encapsulated mitoxantrone and free mitoxantrone were described by a one-compartment model. The release (Rel) of liposome-encapsulated mitoxantrone to free mitoxantrone was determined to be 0.0191 L/h, and the V of liposome-encapsulated mitoxantrone was 2.32 L. The apparent CL of free mitoxantrone was estimated at 1.66 L/h. The apparent V of free mitoxantrone was 35.8 L in patients with relapsed/refractory lymphoma and 22.2 L for patients with SCLC. In patients with relapsed/refractory lymphoma, lower maximum concentration (C max ) and higher apparent V of free mitoxantrone were observed compared with patients with SCLC., Conclusion: The popPK characteristics of both liposome-encapsulated and free mitoxantrone in patients with relapsed/refractory lymphoma or SCLC were effectively described by a one-compartment model., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Developmental myelination is a protracted process in the mammalian brain 1 . One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age 2-4 . We tested this theory in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity 5 . During adolescence, visual experience modulated the rate of oligodendrocyte maturation in visual cortex. To determine whether oligodendrocyte maturation in turn regulates neuronal plasticity, we genetically blocked oligodendrocyte differentiation and myelination in adolescent mice. In adult mice lacking adolescent oligodendrogenesis, a brief period of monocular deprivation led to a significant decrease in visual cortex responses to the deprived eye, reminiscent of the plasticity normally restricted to adolescence. This enhanced functional plasticity was accompanied by a greater turnover of dendritic spines and coordinated reductions in spine size following deprivation. Furthermore, inhibitory synaptic transmission, which gates experience-dependent plasticity at the circuit level, was diminished in the absence of adolescent oligodendrogenesis. These results establish a critical role for oligodendrocytes in shaping the maturation and stabilization of cortical circuits and support the concept of developmental myelination acting as a functional brake on neuronal plasticity., (© 2024. The Author(s).)

Freshwater biodiversity is increasingly threatened by dams and many other anthropogenic stressors, yet our understanding of the complex responses of different biotas and their multiple facets remains limited. Here, we present a multi-faceted and integrated-indices approach to assess the differential responses of freshwater biodiversity to multiple stressors in the Yangtze River, the third longest and most dam-densely river in the world. By combining individual biodiversity indices of phytoplankton, zooplankton, periphyton, macroinvertebrates, and fish with a novel integrated aquatic biodiversity index (IABI), we disentangled the effects of hydrology, water quality, land use, and natural factors on both α and β diversity facets in taxonomic, functional, and phylogenetic dimensions. Our results revealed that phytoplankton and fish species and functional richness increased longitudinally, while fish taxonomic and phylogenetic β diversity increased but phytoplankton and macroinvertebrate β diversity remained unchanged. Hydrology and water quality emerged as the key drivers of all individual biodiversity indices, followed by land use and natural factors, with fish and phytoplankton showed the strongest responses. Importantly, we found that natural, land use, and hydrological factors indirectly affected biodiversity by altering water quality, which in turn directly influenced taxonomic and phylogenetic IABIs. Our findings highlight the complex interplay of multiple stressors in shaping freshwater biodiversity and underscore the importance of considering both individual and integrated indices for effective conservation and management. We propose that our multi-faceted and integrated-indices approach can be applied to other large, dam-modified river basins globally., Competing Interests: The authors declare that there is no competing conflict of interest., (© 2024 The Authors.)

Background: In recent years, the incidence of Parkinson's disease has gradually increased, and the application of dopamine drugs has been limited, so there is an urgent need to explore a more effective treatment method to treat Parkinson's disease effectively treated. Subthalamic nucleus-deep brain stimulation and globus pallidus internus-deep brain Subthalamic nucleus-deep brain stimulation and globus pallidus internus-deep brain stimulation are the two treatments for Parkinson's disease. However, there is no clear conclusion as to which of these two methods is more effective., Primary Study Objective: To compare the effects of deep brain stimulation in the globus pallidus internus and deep brain stimulation in the subthalamic nucleus combined with drugs for Parkinson's disease, respectively., Methods: In order to compare the motor function, neurological function, and activities of daily living scores, the incidence of fluctuations in isokinetic and motor symptoms, changes in medication doses, and the incidence of complications between the two groups, 52 patients treated with globus pallidus internus-deep brain stimulation and 52 patients treated with subthalamic nucleus-deep brain stimulation were included., Primary Outcome Measures: Using the Motor Function Examination scale of the Unified Parkinson's Disease Rating Scale, patients' motor function was evaluated prior to surgery, one month after surgery, three months after surgery, and six months following surgery. The Montreal Cognitive Assessment, the Mini-mental State Examination, and the Activity of Daily Living scale were used to evaluate patients' cognitive function before and three months after surgery. The patient's dose of medication and complications were also counted, among other things., Results: The Unified Parkinson's Disease Rating Scale-Ⅲ scores decreased, and the Montreal Cognitive Assessment, Mini-mental State Examination, and Activity of Daily Living scales increased in both groups after surgery, with no difference between the two groups (P > .05). Between the two groups, there was no difference in the frequency of allodynia and motor symptom variations (P > .05). Postoperatively, the Group globus pallidus internus experienced lower medication doses and a reduced incidence of complications than the Group subthalamic nucleus (P < .05)., Conclusion: The effects of GPi-DBS and STN-DBS in treating PD are both more significant and there is no difference between them, but GPi-DBS reduces complications and medication dose, and has a higher safety profile, indicating that GPi-DBS is more suitable for clinical application and promotion. Future studies need to further explore the mechanism behind the reduction of complications and medication dose of GPi-DBS in Parkinson's disease, in order to provide better support for the clinical application of GPi-DBS.

Background: Laparoscopic common bile duct exploration (LCBDE) is a minimally invasive procedure for the removal of bile duct stones that is often performed by experienced hepatobiliary surgeons; beginners do not easily master this approach., Aim: To investigate the effectiveness and practicality of a three-dimensional printed (3DP) anatomical model based on radiographic images in the training of LCBDE techniques and formulate standardized educational workflows., Methods: Colored LCBDE training models were produced using 3DP technology. Twenty standardized training trainees were randomly divided into two groups: a 3DP model training group and a traditional laparoscopic simulation training group. Both groups received the same number of teaching hours. After a 4-weeks training course, the trainees' subjective and objective progress in basic knowledge and manipulations were evaluated and compared., Results: Compared with traditional laparoscopic simulation, 3DP model simulation training is of great significance in improving trainers' understanding of surgical procedures and cooperation during the operation. Trainees with 3DP models training demonstrated a significant improvement in their understanding of the key points of surgery (χ2 = 6.139, p  = 0.013) and skills scores, especially in core procedural steps operation. More importantly, the trainees showed higher levels of satisfaction and self-confidence while assisting in the surgery., Conclusion: With the development of 3DP models, improvements in the learning effect for theoretical understanding and practical skills were significant. The present study is the initial educational experience with 3DP models to facilitate the operational capabilities of the trainees for LCBDE., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Microglia-mediated neuroinflammation is closely associated with many neurodegenerative diseases. Psoralen has potential for the treatment of many diseases, however, the anti-neuroinflammatory and neuroprotective effects of psoralen have been unclear. This study investigated the anti-neuroinflammatory and neuroprotective effects of psoralen and its regulation of microglial M1/M2 polarization. The LPS-induced mice model was used to test anti-neuroinflammatory effects, regulatory effects on microglia polarization, and neuroprotective effects of psoralen in vivo. The LPS-induced BV2 model was used to test the anti-neuroinflammatory effects and the regulatory effects and mechanisms on microglial M1/M2 polarization of psoralen in vitro. PC12 cell model induced by conditioned medium of BV2 cells was used to validate the protective effects of psoralen against neuroinflammation-induced neuronal damage. These results showed that psoralen inhibited the expression of iNOS, CD86, and TNF-α, and increased the expression of Arg-1, CD206, and IL-10. These results indicated that psoralen inhibited the M1 microglial phenotype and promoted the M2 microglial phenotype. Further studies showed that psoralen inhibited the phosphorylation of Fyn and PKCδ, thereby inhibiting activation of the MAPKs and NF-κB pathways and suppressing the expression of pro-inflammatory cytokines in microglia. Furthermore, psoralen reduced oxidative stress, neuronal damage, and apoptosis via inhibition of neuroinflammation. For the first time, this study showed that psoralen protected neurons and alleviated neuroinflammation by regulating microglial M1/M2 polarization, which may be mediated by inhibition of the Fyn-PKCδ pathway. Thus, psoralen may be a potential agent in the treatment of neuroinflammation-related diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Increased oxidative stress (OS) activity following intracerebral hemorrhage (ICH) had significantly impacting patient prognosis. Identifying optimal genes associated with OS could enhance the understanding of OS after ICH., Methods: We employed single-cell RNA sequencing (scRNA-seq) to investigate the heterogeneity of OS across various cellular tiers following ICH, aiming to acquire biological insights into ICH. We utilized AUCell, Ucell, singscore, ssgsea, and AddModuleScore algorithms, along with correlation analysis, to identify hub genes influencing high OS post-ICH. Furthermore, we employed four machine learning algorithms, eXtreme Gradient Boosting, Boruta, Random Forest, and Least Absolute Shrinkage and Selection Operator, to identify the optimal feature genes. To validate the accuracy of our analysis, we conducted validation in ICH animal experiments., Results: After analyzing the scRNA-seq dataset using various algorithms, we found that OS activity exhibited heterogeneity across different cellular layers following ICH, with particularly heightened activity observed in monocytes. Further integration of bulk data and machine learning algorithms revealed that ANXA2 and COTL1 were closely associated with high OS after ICH. Our animal experiments demonstrated an increase in OS expression post-ICH. Additionally, the protein expression of ANXA2 and COTL1 was significantly elevated and co-localized with microglia. Pearson correlation coefficient analysis revealed a significant correlation between ANXA2 and OS, indicating strong consistency (r = 0.84, p < 0.05). Similar results were observed for COTL1 and OS (r = 0.69, p < 0.05)., Conclusions: Following ICH, ANXA2 and COTL1 might penetrate the brain via monocytes, localize within microglia, and enhance OS activity. This might help us better understand OS after ICH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this paper, a fast positioning platform (FPP) is proposed, able to meet simultaneously the requirements of large stroke and high frequency response, developed based on a PZT (piezoelectric actuator) and a quad-parallel flexible mechanism, for application in precision machining. The FPP is driven by a high-stiffness PZT and guided by a flexible hinge-based mechanism with a quad-parallel flexible hinge. The proposed quad-parallel flexible hinge mechanism can provide excellent planar motion capability with high stiffness and good guiding performance, thus guaranteeing outstanding dynamics characteristics. The mechanical model was established, the input and output characteristics of the FPP were analyzed, and the working range (output displacement and frequency) of the FPP was determined. Based on the mechanical model and the input and output characteristics of the FPP, the design method is described for of the proposed FPP, which is capable of achieving a large stroke while responding at a high frequency. The characteristics of the FPP were investigated using finite element analysis (FEA). Experiments were conducted to examine the performance of the FPP; the natural frequency of the FPP was 1315.6 Hz, while the maximum output displacement and the motion resolution of the FPP in a static state were 53.13 μm and 5 nm, respectively. Step response testing showed that under a step magnitude of 50 μm, the stabilization times for the falling and rising edges of the moving platform were 37 ms and 26 ms, respectively. The tracking errors were about ±1.96 μm and ±0.59 μm when the amplitude and frequency of the signal were 50 μm, 50 Hz and 10 μm, 200 Hz, respectively. The FPP showed excellent performance in terms of fast response and output displacement. The cutting test results indicated that compared with the uncontrolled condition, the values of surface roughness under controlled conditions decreased by 23.9% and 12.7% when the cutting depths were 5 μm and 10 μm, respectively. The developed FPP device has excellent precision machining performance.

Biological or biomimetic membranes are examples within the larger material class of flexible ultrathin lamellae and contoured fluid sheets that require work or energy to impose bending deformations. Bending elasticity also dictates the interactions and assembly of integrated phases or molecular clusters within fluid lamellae, for instance enabling critical cell functions in biomembranes. More broadly, lamella and other thin fluids that integrate dispersed objects, inclusions, and phases behave as contoured 2D colloidal suspensions governed by elastic interactions. To elucidate the breadth of interactions and assembled patterns accessible through elastic interactions, we consider the bending elasticity-driven assembly of 1-10 μm solid plate-shaped Brownian domains (the 2D colloids), integrated into a fluid phospholipid membrane (the 2D fluid). Here, the fluid membranes of giant unilamellar vesicles, 20-50 μm in diameter, each contain 4-100 monodisperse plate-domains at an overall solid area fraction of 17 ± 3%. Three types of reversible plate arrangements are found: persistent vesicle-encompassing quasi-hexagonal lattices, persistent closely associated chains or concentrated lattices, and a dynamic disordered state. The interdomain distances evidence combined attractive and repulsive elastic interactions up to 10 μm, far exceeding the ranges of physio-chemical interactions. Bending contributions are controlled through membrane slack (excess area) producing, for a fixed composition, a sharp cooperative multibody transition in plate arrangement, while domain size and number contribute intricacy., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Chronic exposure to the hypobaric hypoxia environment of plateau could influence human cognitive behaviours which are supported by dynamic brain connectivity states. Until now, how functional connectivity (FC) of the brain network changes with altitudes is still unclear. In this article, we used EEG data of the Go/NoGo paradigm from Weinan (347 m) and Nyingchi (2950 m). A combination of dynamic FC (dFC) and the K-means cluster was employed to extract dynamic FC states which were later distinguished by graph metrics. Besides, temporal properties of networks such as fractional windows (FW), transition numbers (TN) and mean dwell time (MDT) were calculated. Finally, we successfully extracted two different states from dFC matrices where State 1 was verified to have higher functional integration and segregation. The dFC states dynamically switched during the Go/NoGo tasks and the FW of State 1 showed a rise in the high-altitude participants. Also, in the regional analysis, we found higher state deviation in the fronto-parietal cortices and enhanced FC strength in the occipital lobe. These results demonstrated that long-term exposure to the high-altitude environment could lead brain networks to reorganize as networks with higher inter- and intra-networks information transfer efficiency, which could be attributed to a compensatory mechanism to the compromised brain function due to the plateau environment. This study provides a new perspective in considering how the plateau impacted cognitive impairment., (© The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: The metabolic tumour area (MTA) was found to be a promising predictor of prostate cancer. However, the role of MTA based on 18 F-FDG PET/CT in diffuse large B-cell lymphoma (DLBCL) prognosis remains unclear. This study aimed to elucidate the prognostic significance of MTA and evaluate its incremental value to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) for DLBCL patients treated with first-line R-CHOP regimens., Methods: A total of 280 consecutive patients with newly diagnosed DLBCL and baseline 18 F-FDG PET/CT data were retrospectively evaluated. Lesions were delineated via a semiautomated segmentation method based on a 41% SUVmax threshold to estimate semiquantitative metabolic parameters such as total metabolic tumour volume (TMTV) and MTA. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values. Progression-free survival (PFS) and overall survival (OS) were the endpoints that were used to evaluate the prognosis. PFS and OS were estimated via Kaplan‒Meier curves and compared via the log-rank test., Results: Univariate analysis revealed that patients with high MTA, high TMTV and NCCN-IPI ≥ 4 were associated with inferior PFS and OS (P < 0.0001 for all). Multivariate analysis indicated that MTA remained an independent predictor of PFS and OS [hazard ratio (HR), 2.506; 95% confidence interval (CI), 1.337-4.696; P = 0.004; and HR, 1.823; 95% CI, 1.005-3.310; P = 0.048], whereas TMTV was not. Further analysis using the NCCN-IPI model as a covariate revealed that MTA and NCCN-IPI were still independent predictors of PFS (HR, 2.617; 95% CI, 1.494-4.586; P = 0.001; and HR, 2.633; 95% CI, 1.650-4.203; P < 0.0001) and OS (HR, 2.021; 95% CI, 1.201-3.401; P = 0.008; and HR, 3.869; 95% CI, 1.959-7.640; P < 0.0001; respectively). Furthermore, MTA was used to separate patients with high NCCN-IPI risk scores into two groups with significantly different outcomes., Conclusions: Pre-treatment MTA based on 18 F-FDG PET/CT and NCCN-IPI were independent predictor of PFS and OS in DLBCL patients treated with R-CHOP. MTA has additional predictive value for the prognosis of patients with DLBCL, especially in high-risk patients with NCCN-IPI ≥ 4. In addition, the combination of MTA and NCCN-IPI may be helpful in further improving risk stratification and guiding individualised treatment options., Trial Registration: This research was retrospectively registered with the Ethics Committee of the Third Affiliated Hospital of Soochow University, and the registration number was approval No. 155 (approved date: 31 May 2022)., (© 2024. The Author(s).)

Axons have intrinsically poor regenerative capacity in the mature central nervous system (CNS), leading to permanent neurological impairments in individuals. There is growing evidence that exercise is a powerful physiological intervention that can obviously enhance cell rejuvenate capacity, but its molecular mechanisms that mediate the axonal regenerative benefits remain largely unclear. Using the eye as the CNS model, here it is first indicated that placing mice in an exercise stimulation environment induced DNA methylation patterns and transcriptomes of retinal ganglion cell, promoted axon regeneration after injury, and reversed vision loss in aged mice. These beneficial effects are dependent on the DNA demethylases TET3-mediated epigenetic effects, which increased the expression of genes associated with the regenerative growth programs, such as STAT3, Wnt5a, Klf6. Exercise training also shows with the improved mitochondrial and metabolic dysfunction in retinas and optic nerves via TET3. Collectively, these results suggested that the increased regenerative capacity induced by enhancing physical activity is mediated through epigenetic reprogramming in mouse model of optic nerve injury and in aged mouse. Understanding the molecular mechanism underlying exercise-dependent neuronal plasticity led to the identification of novel targets for ameliorating pathologies associated with etiologically diverse diseases., (© 2024 Wiley‐VCH GmbH.)

Objectives: The economic implications of combining rezvilutamide with androgen deprivation therapy (ADT) remain uncertain, despite the observed survival advantages compared with bicalutamide plus ADT. Therefore, this study evaluates the cost-effectiveness of rezvilutamide plus ADT as the first-line treatment of metastatic hormone-sensitive prostate cancer (mHSPC) from the perspective of the Chinese healthcare system., Design: A partitioned survival model was developed to assess the cost-effectiveness of rezvilutamide combined with ADT. Clinical data were obtained from the CHART trial. Costs and utility values were obtained from local estimate and published literature. Only direct medical costs were included in the model., Interventions: Rezvilutamide was administered at 240 mg daily or bicalutamide at 50 mg daily until progression., Outcome Measures: The main outputs of the model included costs and quality-adjusted life years (QALYs), which were used to determine the incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analysis (PSA) were used to explore model uncertainties., Results: The rezvilutamide group showed an expected gain of 2.28 QALYs and an incremental cost of US$60 758.82 compared with the bicalutamide group. The ICER for rezvilutamide group versus bicalutamide group was US$26 656.94 per QALY. The variables with the greatest impact on the model results were the utility for progression-free survival state and the price of rezvilutamide. PSA revealed that rezvilutamide group had 100% probability of being cost-effective at a willingness-to-pay threshold of US$35707.5 per QALY., Conclusion: Rezvilutamide in combination with ADT is more cost-effective compared with bicalutamide plus ADT as the first-line treatment of mHSPC from the perspective of the Chinese healthcare system., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Biological ion channels exhibit high selectivity and permeability of ions because of their asymmetrical pore structures and surface chemistries. Here, we demonstrate a biomimetic nanofluidic channel (BNC) with an asymmetrical structure and glycyl-L-proline (GLP) -functionalization for ultrafast, selective, and unidirectional Dy 3+ extraction over other lanthanide (Ln 3+ ) ions with very similar electronic configurations. The selective extraction mainly depends on the amplified chemical affinity differences between the Ln 3+ ions and GLPs in nanoconfinement. In particular, the conductivities of Ln 3+ ions across the BNC even reach up to two orders of magnitude higher than in a bulk solution, and a high Dy 3+ /Nd 3+ selectivity of approximately 60 could be achieved. The designed BNC can effectively extract Dy 3+ ions with ultralow concentrations and thereby purify Nd 3+ ions to an ultimate content of 99.8 wt.%, which contribute to the recycling of rare earth resources and environmental protection. Theoretical simulations reveal that the BNC preferentially binds to Dy 3+ ion due to its highest affinity among Ln 3+ ions in nanoconfinement, which attributes to the coupling of ion radius and coordination matching. These findings suggest that BNC-based ion selectivity system provides alternative routes to achieving highly efficient lanthanide separation., (© 2024. The Author(s).)

Objective: Intellectual disability (ID) is a prevalent comorbidity in children with cerebral palsy (CP), presenting significant challenges to individuals, families and society. This study aims to develop a predictive model to assess the risk of ID in children with CP., Methods: We analyzed data from 885 children diagnosed with CP, among whom 377 had ID. Using least absolute shrinkage and selection operator regression, along with univariate and multivariate logistic regression, we identified key predictors for ID. Model performance was evaluated through receiver operating characteristic curves, calibration plots, and decision curve analysis (DCA). Bootstrapping validation was also employed., Results: The predictive nomogram included variables such as preterm birth, CP subtypes, Gross Motor Function Classification System level, MRI classification category, epilepsy status and hearing loss. The model demonstrated strong discrimination with an area under the receiver operating characteristic curve (AUC) of 0.781 (95% CI: 0.7504-0.8116) and a bootstrapped AUC of 0.7624 (95% CI: 0.7216-0.8032). Calibration plots and the Hosmer-Lemeshow test indicated a good fit (χ 2 = 7.9061, p = 0.4427). DCA confirmed the model's clinical utility. The cases were randomly divided into test group and validation group at a 7:3 ratio, demonstrating strong discrimination, good fit and clinical utility; similar results were found when stratified by sex., Conclusions: This predictive model effectively identifies children with CP at a high risk for ID, facilitating early intervention strategies. Stratified risk categories provide precise guidance for clinical management, aiming to optimize outcomes for children with CP by leveraging neuroplasticity during early childhood., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Purposes: To investigate the value of machine learning-based radiomics for predicting disease-free survival (DFS) and overall survival (OS) undergoing concurrent chemoradiotherapy (CCRT) for patients with locally advanced cervical cancer (LACC)., Materials and Methods: In this multicentre study, 700 patients with IB2-IVA cervical cancer who underwent CCRT with ongoing follow-up were retrospectively analyzed. Three-dimensional radiomics features of primary lesions and its surrounding 5 mm region in T2WI sequences were collected. Six machine learning methods were used to construct the optimal radiomics model for accurate prediction of DFS and OS after CCRT in LACC patients. Eventually, TCGA and GEO databases were used to explore the mechanisms of radiomics in predicting the progression and survival of cervical cancer. This study adhered CLEAR for reporting and its quality was assessed using RQS and METRICS., Results: In the prediction of DFS, the RSF model combined tumor and peritumor radiomics demonstrated the best predictive efficacy, with the AUC for predicting 1-year, 3-year, and 5-year DFS in the training, validation, and test sets of 0.986, 0.989, 0.990, and 0.884, 0.838, 0.823, and 0.829, 0.809, 0.841, respectively. In the prediction of OS, the GBM model best performer, with AUC of 0.999, 0.995, 0.978, and 0.981, 0.975, 0.837, and 0.904, 0.860, 0.905. Differential genes in TCGA and GEO suggest that the prediction of radiomics model may be associated with KDELR2 and HK2., Conclusion: Machine learning-based radiomics models help to predict DFS and OS after CCRT in LACC patients, and the combination of tumor and peritumor information has higher predictive efficacy, which can provide a reliable basis for therapeutic decision-making in cervical cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Levulinic acid, a hydrolysis product of lignocellulose, can be metabolized into important compounds in the field of medicine and pesticides by engineered strains of Saccharomyces cerevisiae. Levulinic acid, as an intermediate product widely found in the conversion process of lignocellulosic biomass, has multiple applications. However, its toxicity to Saccharomyces cerevisiae reduces its conversion efficiency, so screening Saccharomyces cerevisiae genes that can tolerate levulinic acid becomes the key. By creating a whole-genome knockout library and bioinformatics analysis, this study used the phenotypic characteristics of cells as the basis for screening and found the HMX1 gene that is highly sensitive to levulinic acid in the oxidative stress pathway. After knocking out HMX1 and treating with levulinic acid, the omics data of the strain revealed that multiple affected pathways, especially the expression of 14 genes related to the cell wall and membrane system, were significantly downregulated. The levels of acetyl-CoA and riboflavin decreased by 1.02-fold and 1.44-fold, respectively, while the content of pantothenic acid increased. These findings indicate that the cell wall-membrane system, as well as the metabolism of acetyl-CoA and riboflavin, are important in improving the resistance of Saccharomyces cerevisiae to levulinic acid. They provide theoretical support for enhancing the tolerance of microorganisms to levulinic acid, which is significant for optimizing the conversion process of lignocellulosic biomass to levulinic acid., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Chen, Li, Xin, Xiao, Chen, Yang, Mou, Li, Lu, Fu, Long, Liao, Han, Feng, Li, Zhou, Yang, Yang, Ma and Wang.)

Previous studies have verified that celastrol (Cel) protects against rheumatoid arthritis (RA) by inhibiting the NLRP3 inflammasome signaling pathway, but the molecular mechanism by which Cel regulates NLRP3 has not been clarified. This study explored the specific mechanisms of Cel in vitro and in vivo. A type II collagen-induced arthritis (CIA) mouse model was used to study the antiarthritic activity of Cel; analysis of paw swelling, determination of the arthritis score, and pathological examinations were performed. The antiproliferative and antimigratory effects of Cel on TNF-α induced fibroblast-like synoviocytes (FLSs) were tested. Proinflammatory factors were evaluated using enzyme-linked immunosorbent assay (ELISA). The expression of NF-κB/NLRP3 pathway components was determined by western blotting and immunofluorescence staining in vitro and in vivo. The putative binding sites between Cel and Hsp90 were predicted through molecular docking, and the binding interactions were determined using the Octet RED96 system and coimmunoprecipitation. Cel decreased arthritis severity and reduced TNF-α-induced FLSs migration and proliferation. Additionally, Cel inhibited NF-κB/NLRP3 signaling pathway activation, reactive oxygen species (ROS) production, and proinflammatory cytokine secretion. Furthermore, Cel interacted directly with Hsp90 and blocked the interaction between Hsp90 and NLRP3 in FLSs. Our findings revealed that Cel regulates NLRP3 inflammasome signaling pathways both in vivo and in vitro. These effects are induced through FLSs inhibition of the proliferation and migration by blocking the interaction between Hsp90 and NLRP3., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the therapeutic effect of palmar ginseng on cognitive impairment in rats with type 2 diabetes, evaluate its neuroprotective effects, and explore its underlying mechanism., Methods: A rat model of diabetic cognitive impairment (DCI) was established by feeding with homemade high-fat, high-sugar chow combined with intraperitoneal injection of streptozotocin (STZ). Rats were continually fed high-fat, high-sugar chow for 60 days after successful induction of the model. Palmar ginseng was administered via gavage. The Morris test was performed after 30 days of treatment. At the end of the test, blood samples were collected, and the activities of IL-6, IL-10, TNF-α, and IL-1β in rat serum. Pathological changes in hippocampal tissues were observed by Haematoxylin-eosin (HE) staining of the brain, activation of microglia in hippocampal tissues was detected by immunofluorescence, and the expression of PI3K/Akt/mTOR and JAK2/STAT3 proteins in the hippocampal tissues by Western blot., Results: During the administration of palmar Ginseng, the body weight and blood glucose levels of DCI rats were measured weekly, with results showing that Palmar Ginseng effectively reduced blood glucose levels and body weight of DCI rats. Behavioural tests in the water maze indicated that palmar ginseng effectively improved the learning and memory ability of DCI rats. HE and immunofluorescence staining showed that palmar ginseng improved DCI in rats, ameliorated hippocampal neuronal damage, and improved microglial activation. ELISA showed that palmar ginseng significantly reduced the expression of pro-inflammatory factors in the serum of DCI rats. Increased expression of anti-inflammatory factors was observed, and Western blot analysis showed that Palmar Ginseng regulated PI3K/Akt/mTOR and JAK2/STAT3 protein expression, promoted the phosphorylation of PI3K/Akt/mTOR, and inhibited JAK2/STAT3 protein phosphorylation in rat hippocampal tissues as well as in BV2 cells., Conclusions: Palmar ginseng may improve the onset and development of DCI by upregulating the phosphorylation of proteins in the PI3K/Akt/mTOR pathway., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Objective: The objective of this study was to identify the risk factors for postoperative pathological escalation of endometrial cancer in patients with a pathologic diagnosis of endometrial intraepithelial neoplasia (EIN) before surgery. Some of the clues from the preoperative assessment were used to build a nomogram to predict the likely pathological escalation after surgery, and to explore the feasibility of sentinel lymph node biopsy in these patients with possible pathological escalation., Methods: This was a retrospective analysis of patients who underwent surgical treatment for EIN diagnosed before surgery between 2018 and 2023 in The Obstetrics and Gynecology Hospital of Fudan University. parameters including clinical, radiological and histopathological factors were analyzed by univariate and multivariate logistic regression to determine the correlation with pathology upstaging. A nomogram based on the multivariate results was developed to predict the probability of pathology upstaging. A total of 729 patients were included, divided into training set and validation set. 484 patients were used to build the model. This nomogram was subsequently validated using 245 patients., Results: Upstaging to endometrial carcinoma occurred in 115 (23.8 percent) of 484 women treated between 2018 and 2023 in training set. A lager endometrial thickness (at least 15 mm), menopause, hypertension, HE4, and endometrial blood were significantly associated with upstaging. A nomogram developed using these factors demonstrated good predictive performance (area under the receiver operating characteristic curve (AUC)=0.6808; 95% confidence interval [CI]=0.6246-0.7369). The nomogram showed similar predictive performance in the validation data set, based on another 245 women (AUC=0.7821; 95% CI=0.7076-0.8567)., Conclusion: This study developed a novel nomogram based on the 5 most important factors, which can accurately predict invasive cancer. It is common for women with preoperative diagnosis of EIN to experience pathological progression to endometrial cancer. For some patients with postoperative pathological escalation, we found lymph node metastasis. This nomogram may be useful to help doctor decide whether to perform sentinel lymph node biopsy for surgical staging in these EIN patients. According to the nomogram, simultaneous sentinel lymph node biopsy in patients with high probability of postoperative pathological upgrading can provide better guidance for postoperative adjuvant treatment of endometrial cancer and avoid the occurrence of secondary surgery., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: To investigate the effect of digital scanning combined with reverse engineering technology in the demonstration of full crown tooth preparation., Methods: Thirty-one students were randomly divided into the two groups. The students in the control group carried out traditional demonstration by the use of eye-measurement methods. The students in the experimental group carried out improved demonstration by the use of digital intraoral scan with 3D measurement data. The students in both groups were provided with two resin teeth to conduct full crown tooth preparation on head model dental simulators. The teeth prepared before and after demonstration were scored by Chinese Stomatological Association Group Standards, with a total score of 100 points. Analysis of covariance was performed to comparatively analyze the scores related to the tooth surfaces, and convergence angle between two groups., Results: Analysis of two prepared teeth (tooth #11 and #16) in two groups showed that there was a statistical significant difference in the mean score between the control group and experimental group (tooth #11, P = 0.0039) (tooth #16, P = 0.0120).The demonstration of the tooth #16 showed that there were statistical significant differences in the scores related to buccolingual surface (P = 0.0205) and proximal surface (P = 0.0023) between the control group and experimental group; There was a statistical significant difference in the score related to the convergence angle of buccolingual surface between the control group and experimental group (P = 0.0265)., Conclusion: The digital methods can effectively improve the quality of tooth preparations and has a pedagogical advantage for posterior teeth, which present greater operational challenges.

The neuropeptide 26RFa, a member of the RF-amide peptide family, activates the pyroglutamylated RF-amide peptide receptor (QRFPR), a class A GPCR. The 26RFa/QRFPR system plays critical roles in energy homeostasis, making QRFPR an attractive drug target for treating obesity, diabetes, and eating disorders. However, the lack of structural information has hindered our understanding of the peptide recognition and regulatory mechanism of QRFPR, impeding drug design efforts. In this study, we determined the cryo-EM structure of the G q -coupled QRFPR bound to 26RFa. The structure reveals a unique assembly mode of the extracellular region of the receptor and the N-terminus of the peptide, and elucidates the recognition mechanism of the C-terminal heptapeptide of 26RFa by the transmembrane binding pocket of QRFPR. The study also clarifies the similarities and distinctions in the binding pattern of the RF-amide moiety in five RF-amide peptides and the RY-amide segment in neuropeptide Y. These findings deepen our understanding of the RF-amide peptide recognition, aiding in the rational design of drugs targeting QRFPR and other RF-amide peptide receptors., (© 2024. The Author(s).)

Manganese dioxide (MnO 2 ) is an attractive cathode material for aqueous zinc batteries (AZBs) owing to its environmental benignity, low cost, high operating voltage, and high theoretical capacity. However, the severe dissolution of Mn 2+ leads to rapid capacity decay. Herein, a self-assembled layer of amino-propyl phosphonic acid (AEPA) on the MnO 2 surface, which significantly improves its cycle performance is successfully modified. Specifically, AEPA can be firmly attached to MnO 2 through a strong chemical bond, forming a hydrophobic, and uniform organic coating layer with a few nanometers thickness. This coating layer can significantly inhibit the dissolution of Mn 2+ by avoiding the direct contact between the electrolyte and cathode, thus enhancing the structural integrity and redox reversibility of MnO 2 . As a result, the MnO 2 @AEPA cathode achieves a high reversible capacity of 223 mAh g -1 at 0.5 A g -1 and a high capacity retention of 97% after 1700 cycles at 1 A g -1 . This work provides new insights in developing stable Mn-based cathodes for aqueous batteries., (© 2024 Wiley‐VCH GmbH.)

Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology 1-3 . The γδ T cell receptor (TCR), which is generated by γδ T cells, recognizes a diverse range of antigens independently of the major histocompatibility complex 2 . The γδ TCR associates with CD3 subunits, initiating T cell activation and holding great potential in immunotherapy 4 . Here we report the structures of two prototypical human Vγ9Vδ2 and Vγ5Vδ1 TCR-CD3 complexes 5,6 , revealing two distinct assembly mechanisms that depend on Vγ usage. The Vγ9Vδ2 TCR-CD3 complex is monomeric, with considerable conformational flexibility in the TCRγ-TCRδ extracellular domain and connecting peptides. The length of the connecting peptides regulates the ligand association and T cell activation. A cholesterol-like molecule wedges into the transmembrane region, exerting an inhibitory role in TCR signalling. The Vγ5Vδ1 TCR-CD3 complex displays a dimeric architecture, whereby two protomers nestle back to back through the Vγ5 domains of the TCR extracellular domains. Our biochemical and biophysical assays further corroborate the dimeric structure. Importantly, the dimeric form of the Vγ5Vδ1 TCR is essential for T cell activation. These findings reveal organizing principles of the γδ TCR-CD3 complex, providing insights into the unique properties of γδ TCR and facilitating immunotherapeutic interventions., (© 2024. The Author(s).)

Rheumatoid arthritis (RA) is an autoimmune disease with complex etiology, and its pathological mechanism remains unclear. Our aim was to explore the effect of protein succinylation on RA by silencing Sirt5 , sequencing succinylated proteins, and analyzing the sequencing results to identify potential biomarkers. We wanted to gain a clearer understanding of RA pathogenesis, quantitative assessment of succinylated proteins in Fibroblast-like synoviocytes (FLS) from RA patients using liquid chromatography- tandem mass spectrometry and enrichment analysis investigated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 679 proteins and 2,471 lysine succinylation sites were found in RA patients, and 436 differentially expressed proteins and 1,548 differentially expressed succinylation sites were identified. Among them, 48 succinylation sites were upregulated in 38 proteins and 144 succinylation sites were downregulated in 82 proteins. Bioinformatics showed that succinylated proteins were significantly enriched in amino and fatty acid metabolisms. Results indicated that Sirt5 can affect various biological processes involved in RA FLSs, and succinylation caused by silencing Sirt5 plays a major role in RA progression. This study provides further understanding of RA pathogenesis and may facilitate searching for potential RA biomarkers., Competing Interests: This work was supported by the National Science Fund of China (Grant No.81671624), and Science Fund of Shandong Province (Grant No.ZR2023MH213).The authors have no conflicts of interest to disclose., (2024, International Research and Cooperation Association for Bio & Socio - Sciences Advancement.)

Clostridium perfringens alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of C. perfringens and is the major virulence determinant of C. perfringens type A. CPA induces hemolysis in many species, including humans, murines, sheep and rabbits, through its enzymatic activity, which dissolves the cell membrane. Recent studies have shown that some pore-forming toxins cause hemolysis, which is achieved by the activation of purinergic receptors (P2). However, the relationship between P2 receptors and non-pore-forming toxin hemolysis has not been investigated. In the present study, we examined the function of P2 receptors in CPA toxin hemolysis and found that CPA-induced hemolysis was dependent on P2 receptor activation, and this was also true for Staphylococcus aureus β-Hemolysin, another non-pore-forming toxin. Furthermore, we use selective P2 receptor antagonists to demonstrate that P2X1 and P2X7 play important roles in the hemolysis of human and murine erythrocytes. In addition, we found that redox metabolism was mainly involved in CPA-induced hemolysis using metabolomic analysis. We further demonstrate that CPA activates P2 receptors and then activates NADPH oxidase through the PI3K/Akt and MEK1/ERK1 pathways, followed by the production of active oxygen to induce hemolysis. These findings contribute to our understanding of the pathological effects of CPA, clarify the relationship between P2 activation and non-pore-forming toxin-induced hemolysis, and provide new insights into CPA-induced hemolysis.

Nanotechnology has attracted increasing attention in the field of medical applications due to its significant potential for development. However, one major challenge that has emerged with nanoparticles is their tendency to activate the host immune clearance system, which hampers the achievement of desired therapeutic outcomes and may lead to harmful side effects. In recent years, membrane-coated nanoparticles have emerged as a promising solution, demonstrating their effectiveness in evading immune system clearance. These innovative nanoparticles inherit essential biological attributes from natural cell membranes, such as anchoring proteins and antigens. Consequently, membrane-coated nanoparticles exhibit unique capabilities such as immune evasion, prolonged circulation, targeted drug release, and immune modulation, substantially enhancing their versatility and prospects within the realm of biomedical applications. This review provides a comprehensive overview of the current applications of cell membrane-coated nanoparticles in disease therapy, highlighting their immense potential in this rapidly evolving platform. Additionally, the review outlines the promising prospects of this technology in disease therapy.

Background: Epilepsy is a serious neurological disorder that affects millions of people each year, often leading to cognitive issues and reduced quality of life. Medication is the main treatment, but many patients experience negative side effects. Male Sprague-Dawley (SD) rats were chosen as experimental animals for this experiment due to their physiological and genetic similarities to humans, cost-effectiveness, and ease of handling in a laboratory setting., Aims: The objective of this study was to assess the neuroprotective properties of baicalin (BA) in relation to its impact on anxiety and depressive-like behaviors in the epilepsy model., Methods: Thirty male Sprague-Dawley (SD) rats were selected for this experiment. Pentylenetetrazol (PTZ) kindling (40 mg/kg; i.p.) was utilized to establish an epilepsy model. The effect of BA (50 mg/kg; gavage) on seizure severity (assessed using the Racine scale), anxiety, and depressive- like behaviors (evaluated through open field experiments and forced swimming tests) was examined. Histological examinations, including hematoxylin and eosin (HE) staining and Nissl staining, were conducted to assess neuronal damage. Furthermore, the neuroprotective properties of BA were examined through the analysis of Doublecortin (DCX), MKI67 (KI67), and Brain-Derived Neurotrophic Factor (BDNF) levels in the hippocampus of rats. The inhibitory impact of BA on neuroinflammation was assessed via dual labeling for NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and the microglial marker ionized calcium- binding adapter molecule 1 (Iba-1). The influence of BA on the expression of P2X7 receptor (P2X7R), NLRP3, and Interleukin-1β (IL-1β) was also assessed by reverse transcription quantitative PCR (RT-qPCR) in the brain. Finally, we employed a molecular docking model to assess the extent of receptor-ligand binding., Results: Epilepsy models exhibited significant anxiety and depressive-like behaviors, and BA significantly reduced the severity of seizures in these rats while also alleviating their anxiety and depressive-like behaviors. Moreover, neuronal loss and damage were observed in the hippocampus of epileptic rats, but BA was able to effectively counteract this issue by enhancing BDNF expression and promoting neurogenesis within the hippocampus, especially in the DG region. The co-localization of Iba-1 with NLRP3 indicated the activation of NLRP3 inflammasome in microglia. Subsequent RT-PCR revealed that BA may alleviate anxiety and depressive-like behaviors in epileptic rats by activating the P2RX7/NLRP3/ IL-1β signaling pathway. The final molecular docking results indicated that BA had a good binding affinity with proteins, such as P2RX7, NLRP3, and IL-1β., Conclusion: This study confirmed the effectiveness of BA in improving anxiety and depressivelike behaviors associated with epilepsy. Moreover, it provides theoretical support for the neuroprotective role demonstrated by BA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: We aimed to evaluate and compare the risk of hematological adverse events (AEs) associated with CDK4/6 inhibitors using data from randomized controlled trials (RCTs) and Food and Drug Adverse Event Reporting System (FAERS) database., Methods: The PubMed, Embase, and Cochrane Library databases were searched for RCTs related to abemaciclib, palbociclib, and ribociclib. A network meta-analysis (NMA) was conducted to compare the risks of hematological AEs, and a disproportionality analysis was performed to detect signals of hematological AEs., Results: 16 RCTs comprising 16,350 breast cancer patients were included. Palbociclib and ribociclib had similar risks for hematological AEs, except a higher risk of grade 3-4 leukopenia observed with palbociclib (risk ratio [RR]: 7.84, 95% confidence interval [95%CI]: 1.33-41.28). Abemaciclib had a higher risk of anemia than both ribociclib (grade 1-4: RR: 2.23, 95% CI: 1.25 - 3.96; grade 3-4: RR: 3.52, 95% CI: 1.59 - 8.11) and palbociclib (grade 1-4: RR: 1.65, 95%CI: 1.03 - 2.59), but a lower risk of grade 3-4 of both leukopenia (RR: 0.12, 95%CI: 0.02 - 0.49) and neutropenia (RR: 0.15, 95%CI: 0.04 - 0.52) compared with palbociclib. Signals indicating occurrence of leukopenia, neutropenia, anemia, and thrombocytopenia were identified for three CDK4/6 inhibitors., Conclusion: Abemaciclib, palbociclib, and ribociclib showed significant but inconsistent hematological toxicity risks.

Carrier multiplication (CM) in semiconductors, the process of absorbing a single high-energy photon to form two or more electron-hole pairs, offers great potential for the high-response detection of high-energy photons in the ultraviolet spectrum. However, compared to two-dimensional semiconductors, conventional bulk semiconductors not only face integration and flexibility bottlenecks but also exhibit inferior CM performance. To attain efficient CM for ultraviolet detection, we designed a two-terminal photodetector featuring a unilateral Schottky junction based on a two-dimensional γ-InSe/graphene heterostructure. Benefiting from a strong built-in electric field, the photogenerated high-energy electrons in γ-InSe, an ideal ultraviolet light-absorbing layer, can efficiently transfer to graphene without cooling. It results in efficient CM within the graphene, yielding an ultrahigh responsivity of 468 mA/W and a record-high external quantum efficiency of 161.2% when it is exposed to 360 nm light at zero bias. This work provides valuable insights into developing next-generation ultraviolet photodetectors with high performance and low-power consumption.

Biochar-bound persistent free radicals (biochar-PFRs) attract much attention because they can directly or indirectly mediate the transformation of contaminants in large-scale wastewater treatment processes. Despite this, a comprehensive top-down understanding of the redox activity of biochar-PFRs, particularly consumption and regeneration mechanisms, as well as challenges in redox activity assessment, is still lacking. To tackle this challenge, this review outlines the identification and determination methods of biochar-PFRs, which serve as a prerequisite for assessing the redox activity of biochar-PFRs. Recent developments concerning biochar-PFRs are discussed, with a main emphasis on the reaction mechanisms (both non-free radical and free radical pathways) and their effectiveness in removing contaminants. Importantly, the review delves into the mechanism of biochar-PFRs regeneration, triggered by metal cations, reactive oxygen species, and ultraviolet radiations. Furthermore, this review thoroughly explores the dilemma in appraising the redox activity of biochar-PFRs. Components with unpaired electrons (particular defects and metal ions) interfere with biochar-PFRs signals in electron paramagnetic resonance spectra. Scavengers and extractants of biochar-PFRs also inevitably modify the active ingredients of biochar. Based on these analyses, a practical strategy is proposed to precisely determine the redox activity of biochar-PFRs. Finally, the review concludes by presenting current gaps in knowledge and offering suggestions for future research. This comprehensive examination aims to provide new and significant insights into the redox activity of biochar-PFRs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: We aimed to investigate the cost-effectiveness of tislelizumab plus chemotherapy compared to chemotherapy alone as a first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (OSCC)., Methods: A partitioned survival model was developed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy versus chemotherapy alone in patients with advanced or metastatic OSCC over a 10-year lifetime horizon from the perspective of the Chinese healthcare system. Costs and utilities were derived from the drug procurement platform and published literature. The model outcomes comprised of costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were conducted to address uncertainty and ensure the robustness of the model., Results: Tislelizumab plus chemotherapy yielded an additional 0.337 QALYs and incremental costs of $7,117.007 compared with placebo plus chemotherapy, generating an ICER of $21,116.75 per QALY, which was between 1 time ($12,674.89/QALY) and 3 times GDP ($38,024.67/QALY) per capita. In one-way sensitivity analysis, the ICER is most affected by the cost of oxaliplatin, paclitaxel and tislelizumab. In the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set as 1 or 3 times GDP per capita, the probability of tislelizumab plus chemotherapy being cost-effective was 1% and 100%, respectively., Conclusion: Tislelizumab plus chemotherapy was probably cost-effective compared with chemotherapy alone as the first-line treatment for advanced or metastatic OSCC in China., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 He et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)