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The resistance of osteosarcoma (OS) to ionizing radiation (IR) is an obstacle for effective patient treatment. Apurinic/apyrimidinic endonuclease-reduction/oxidation factor 1 (APE1/Ref-1) is a multifunctional protein with DNA repair and reduction/oxidation (redox) activities. We previously revealed the role of APE1 in OS radioresistance; however, whether the redox activity of APE1 is involved in OS radioresistance is unclear. APE1 regulates the activation of ataxia-telangiectasia mutated (ATM), an initiator of DNA damage response that mediates radioresistance in other cancers. The role of APE1 redox activity and ATM activation in OS radioresistance is unknown. Our study revealed that IR increased APE1 expression and ATM activation in OS cells, and APE1 directly regulated ATM activation by its redox activity. The combined use of an APE1 redox inhibitor and ATM inhibitor effectively sensitized OS cells to IR in vitro and in vivo. Mechanistically, the increased radiosensitization of OS cells by the combined use of the two inhibitors was mediated by increased ferroptosis. Co-treatment with the two inhibitors significantly decreased expression of the common targeted transcription factor P53 compared with single inhibitor treatment. Collectively, APE1 redox activity, ATM activation and their crosstalk play important roles in the resistance of OS to irradiation. Synergetic inhibition of APE1 redox activity and ATM activation sensitized OS cells to IR by inducing ferroptosis, which provides a promising strategy for OS radiotherapy., 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.)

This study investigates the correlation between circulating tumor cells (CTCs) in peripheral blood and the clinical characteristics and prognosis of advanced pediatric neuroblastoma (NB). We conducted a retrospective analysis of 144 children with advanced NB who underwent comprehensive treatment. Detailed clinical data were collected, and CTCs were detected using a negative enrichment method combined with immunofluorescence technology. Prognostic evaluation criteria and cutoff values for CTCs were established using ROC curve analysis. Univariate and Cox multivariate regression analyses identified independent risk factors impacting prognosis. Patients were categorized into high and low-expression groups based on optimal cutoff values determined with X-tile software. The high expression group had a significantly higher incidence of disease progression ( p  < 0.001), maximum tumor diameter ≥10 cm ( p  = 0.004), undifferentiated subtype ( p  = 0.034), and stage IV disease ( p  = 0.007) compared to the low expression group. CTCs were notably higher in patients with progression compared to those with mitigation ( p  < 0.001), in those with maximum tumor diameter ≥10 cm compared to <10 cm ( p  < 0.001), and in stage IV compared to stage III patients ( p  = 0.036). The AUC values for maximum tumor diameter, degree of differentiation, and tumor stage were 0.703, 0.669, 0.574, and 0.598, respectively. The detection of CTCs provides significant insights into the clinical characteristics and prognosis of advanced pediatric NB, highlighting its potential as a prognostic tool.

Study Objective: The lactate-to-albumin ratio (LAR) has been confirmed to be an effective prognostic marker in sepsis, heart failure, and acute respiratory failure. However, the relationship between LAR and mortality in patients with acute respiratory distress syndrome (ARDS) remains unclear. We aim to evaluate the predictive value of LAR for ARDS patients., Design: A retrospective cohort study., Setting: Medical Information Mart for Intensive Care IV (v2.2) database., Patients: 769 patients with acute respiratory distress syndrome(ARDS)., Interventions: We divided the patients into two subgroups according to the primary study endpoint (28-days all-cause mortality): the 28-day survivors and the 28-day non-survivors., Measures: Multivariate Cox Regression, Receiver Operator Characteristic (ROC) and Kaplan-Meier survival analysis were used to investigate the relationship between LAR and short-time mortality in patients with ARDS., Main Results: The 28-day mortality was 38 % in this study. Multivariable Cox regression analysis showed that LAR was an independent predictive factor for 28-day mortality (HR 1.11, 95 %CI: 1.06-1.16, P < 0.001). The area under curve (AUC) of LAR in the ROC was 70.34 % (95 %CI: 66.53 % - 74.15 %) that provided significantly higher discrimination compared with lactate (AUC = 68.00 %, P = 0.0007) or albumin (AUC = 63.17 %, P = 0.002) alone. LAR was also not inferior to SAPSII with the AUC of 73.44 % (95 %CI: 69.84 % - 77.04 %, P = 0.21). Additionally, Kaplan-Meier survival analysis displayed that ARDS patients with high LAR (> the cut-off value 0.9055) had a significantly higher 28-day overall mortality rate (P < 0.001) and in-hospital mortality rate (P < 0.001). However, patients in high LAR group had shorter length of hospital stay (P < 0.001), which might be caused by higher in-hospital mortality., Conclusions: We confirmed that there was a positive correlation between LAR and 28-day mortality. This could provide anesthesiologists and critical care physicians with a more convenient tool than SAPSII without being superior for detecting ARDS patients with poor prognosis timely., Competing Interests: Declaration of competing interest Luo Meng-Qiang reports financial support was provided by Association between lactate-to-albumin ratio and short-time mortality in patients with acute respiratory distress syndrome. Luo Meng-Qiang reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they 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 Inc. All rights reserved.)

Exploring the relationship between semiconductor structure and surface-enhanced Raman scattering (SERS) activity was essential for the development of ultrasensitive SERS substrates. Herein, we report an ytterbium atomic doping strategy to render TiO 2 (Yb-TiO 2 ) highly SERS sensitive superior to pure TiO 2 , with a detection limit as low as 1 × 10 -9 M for 4-mercaptobenzoic acid. First-principles density functional theory calculations reveal that ytterbium doping leads to high electrostatic properties, allowing for significant charge transfer from molecules to semiconductors. Theoretical and experimental results indicate that Yb-TiO 2 has a smaller band gap and higher density of states, which effectively enhance charge transfer between molecules and substrates, resulting in significant SERS activity. More importantly, Yb-TiO 2 was particularly stable in air and acid solution and can be used for trace molecule detection in extreme environments. We demonstrate a promising approach to construct ultrasensitive SERS by optimizing the electronic structure induced by geometric structures.

This study investigated the potential role and underlying mechanisms of oleanolic acid (OA), a pentacyclic triterpene with antioxidant and anti-inflammatory properties, in porcine oocytes during in vitro maturation (IVM). The results showed that supplementation with 5 μM OA during IVM resulted in a greater percentage of mature oocytes, parthenogenetically activated embryos and somatic cell nuclear-transferred embryos. This was evidenced by significant increases in the rate of first polar body expulsion, the expansion of cumulus granulosa cells and the total cell number in blastocysts. Further analysis revealed that OA promoted fatty acid accumulation and upregulated the mRNA expression of genes involved in fatty acid β-oxidation. OA significantly increased the intracellular mitochondrial membrane potential and ATP levels and effectively inhibited BAX/BCL2 and Cleaved Caspase3 protein expression. Notably, OA increased the protein levels of intracellular Nrf2 and HO-1, and the GSH levels and the activities of the antioxidant enzymes SOD and catalase (CAT), while reducing ROS levels. Mechanistically, OA activated the Nrf2/HO-1 signalling pathway, which is crucial for regulating the expression of antioxidant-related targets in IVM porcine oocytes. Our findings indicated that OA improved antioxidant capacity by activating the Nrf2/HO-1 signalling pathway, thereby promoting porcine oocyte maturation., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: In patients with degenerative lumbar diseases, we aimed to establish the cutoff value of Hounsfield units (HU) for osteoporosis screening on the basis of the relationship between computed tomography (CT) HU value and volume bone mineral density (BMD) measured by quantitative computed tomography (QCT)., Methods: A total of 136 patients aged ≥ 50 years with degenerative lumbar diseases were retrospectively included. Their QCT-BMD of L1-2 were recorded, and the CT values of L1-2 were measured with the same CT images of QCT. The degree of bone loss was evaluated with the criteria based on QCT-BMD: cutoff value of 80 mg/cm 3 for osteoporosis and cutoff value of 120 mg/cm 3 for osteopenia. The cutoff of CT value was acquired according to the linear regression equation between CT value and QCT-BMD., Results: The rate of osteoporosis, osteopenia, normal BMD was 33.8% (46/136), 51.5% (70/136), and 14.7% (20/136), respectively. The Pearson correlation coefficients between CT value and QCT-BMD were over 0.9 (P < 0.05). The cutoff of average CT value of L1-2 was calculated and adjusted to 110HU for osteoporosis and 160HU for osteopenia according the equation: average QCT-BMD of L1-2 = 0.76 ✕ average CT value of L1-2-0.46 (R 2  = 0.931, P < 0.001). Cutoff value of 110HU was 91.2% (42/46) sensitive and 88.9% (80/90) specific for identifying osteoporosis. The cutoff value of 160HU was 95.0% (19/20) sensitive and 96.6% (112/116) specific for distinguishing normal BMD from abnormal BMD (osteoporosis and osteopenia)., Conclusion: The CT value is effective in osteoporosis screening, and the QCT-based cutoff value is 110 HU for osteoporosis and 160 HU for osteopenia in the patients with degenerative lumbar disease., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Real-time shear wave elastography (SWE) is a non-invasive imaging technique used to measure tissue stiffness by generating and tracking shear waves in real time. This advanced ultrasound-based method provides quantitative information regarding tissue elasticity, offering valuable insights into the mechanical properties of biological tissues. However, the application of real-time SWE in the musculoskeletal system and sports medicine has not been extensively studied., Aim: To explore the practical value of real-time SWE for assessing Achilles tendon hardness in older adults., Methods: A total of 60 participants were enrolled in the present study, and differences in the elastic moduli of the bilateral Achilles tendons were compared among the following categories: (1) Age: 55-60, 60-65, and 65-70-years-old; (2) Sex: Male and female; (3) Laterality: Left and right sides; (4) Tendon state: Relaxed and tense state; and (5) Tendon segment: Proximal, middle, and distal., Results: There were no significant differences in the elastic moduli of the bilateral Achilles tendons when comparing by age or sex ( P > 0.05). There were, however, significant differences when comparing by tendon side, state, or segment ( P < 0.05)., Conclusion: Real-time SWE plays a significant role compared to other examination methods in the evaluation of Achilles tendon hardness in older adults., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: β-glucan has been reported to be a potential natural immune modulator for tumor growth inhibition. We aimed to evaluate the efficacy and safety of β-glucan plus immunotherapy and chemotherapy in the first-line treatment of advanced gastric adenocarcinoma., Methods: This is a phase IB, prospective, single-arm, investigator-initiated trail. Advanced gastric adenocarcinoma patients received β-glucan, camrelizumab, oxaliplatin, oral S-1 every 3 weeks. The curative effect was evaluated every 2 cycles. The primary endpoints were objective response rate (ORR) and safety, with secondary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). The exploratory endpoint explored biomarkers of response to treatment efficacy., Results: A total of 30 patients had been enrolled, including 20 (66.7%) males and all patients with an ECOG PS score of ≥1. The ORR was 60%, the mPFS was 10.4 months (95% confidence interval [CI], 9.52-11.27), the mOS was 14.0 months (95% CI, 11.09-16.91). A total of 19 patients (63.3%) had TRAEs, with 9 patients (30%) with grade ≥ 3. The most common TRAEs were nausea (53.3%). After 2 cycles of treatment, the levels of IL-2, IFN-γ and CD4+ T cells significantly increased ( P < 0.05). Furthermore, biomarker analysis indicated that patient with better response and longer OS exhibited lower GZMA expression at baseline serum., Conclusions: This preliminary study demonstrates that β-glucan plus camrelizumab and SOX chemotherapy offers favorable efficacy and a manageable safety profile in patients with advanced gastric adenocarcinoma, and further studies are needed to verify its efficacy and safety., Clinical Trial Registration: Chinese Clinical Trials Registry, identifier ChiCTR2100044088., Competing Interests: Authors CZ, XZ and DC were employed by Jiangsu Simcere Diagnostics Co., Ltd. The remaining 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 Chu, He, Xue, Jiang, Zhu, Qi, Zhang, Chen, Dai, Xian and Zhu.)

The energy system of lithium-sulfur batteries is quite promising, however, lithium-sulfur batteries still suffer from considerable problems, such as the abominable shuttle effect of polysulfides (LiPSs), the low conductivity of the solid-phase products, the slow redox kinetics during charging and discharging, and the volume expansion. Herein, the hybridization pattern between the d-orbitals of various transition metal atoms and the p-orbitals of sulfides is revealed grounded in the theory of density function, which explains the high adsorption strength of two-dimensional metal-organic frameworks (MOFs) with LiPSs and accelerates the screening of high-performance anchoring and catalytic materials. The results elucidate that the coordinated transition metal-organic frameworks (Mo-NH MOF) monolayers increase the capacity of LiPSs to anchor by forming more π-bonds from the hybridization of the S p orbitals and Mo d orbitals. Notably, Mo-NH MOF exhibits bifunctional catalytic activity for sulfur reduction as well as Li 2 S decomposition reactions during charging and discharging, which improves the conversion efficiency of redox reactions. As a result, new MOF materials featuring unique active centers and the potential mechanism by which the active centers modulate the performance of the substrate materials are revealed, and this finding may accelerate the development of high-performance Li-S batteries., 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 Inc. All rights reserved.)

Objective: Oleanolic acid (OA) is a pentacyclic triterpenoid with antioxidant activity that can be an effective scavenger of free radicals in cells. This study was designed to investigate the effects of OA on porcine early embryo developmental competence in vitro and its possible mechanisms of action., Methods: In the present study, parthenogenetically activated porcine embryos were used as models to assess the effect of OA on the in vitro developmental capacity of early porcine embryos in vitro. Zygotic genome activation, mitochondrial function, oxidative stress, cell proliferation and apoptosis in early porcine embryos were examined after supplementing the culture medium with 5 μM OA., Results: The results showed that 5 μM OA supplementation not only significantly increased the blastocyst diameter in early porcine embryos on day 6 but also increased the total number of blastocysts. Furthermore, OA supplementation increased the blastocyst proliferation rate and decreased blastocyst apoptosis. Moreover, OA supplementation significantly increased the proportion of embryos that developed to the 4-cell stage after 48 h of in vitro culture and upregulated the expression of genes associated with zygotic genome activation (DPPA2 and ZSCAN4). Notably, OA alleviated oxidative stress by reducing the intracellular levels of reactive oxygen species and increasing the intracellular levels of reduced glutathione at the 4-cell stage and increased the activities of superoxide dismutase and catalase. Concurrently, OA significantly increased the mitochondrial membrane potential and intracellular ATP content., Conclusion: These results suggest that OA promotes the in vitro developmental competence of parthenogenetically activated porcine embryos by reducing oxidative stress and improving mitochondrial function during in vitro culture and that OA may contribute to the efficiency of in vitro embryo production.

Background: Apoptosis has been recognized as a critical pathophysiological process during cerebral ischemia. The neuroprotective effect of CART on ischemic brain injury is determined. However, there is little research on the protective effect of CART on neural stem cells (NSCs)., Methods: Primary cultured rat NSCs were utilized as the research subject. In vitro oxygen glucose deprivation (OGD) treatment was employed, and NSCs were extracted from SD pregnant rats following previous experimental protocols and identified through cell immunofluorescence staining. The appropriate concentration of CART affecting OGD NSCs was initially screened using Cell Counting Kit-8 (CCK-8) and Lactate Dehydrogenase (LDH) assays. EdU staining and Western blotting (WB) techniques were employed to assess the impact of the suitable CART concentration on the proliferation and apoptosis of OGD NSCs. Finally, Western blot analysis was conducted to investigate the cAMP-response element binding protein (CREB) pathway and expression levels of related proteins after KG-501 treatment in order to elucidate the mechanism underlying apoptosis and proliferation regulation in OGD NSCs., Results: CCK-8 and LDH assays indicated that a concentration of 0.8 nM CART may be the optimal concentration for modulating the proliferation of OGD NSCs. Subsequently, cellular immunofluorescence and EdU detection experiments further confirmed the findings obtained from CCK-8 analysis. Western blot analysis of apoptosis-related protein expression also demonstrated that an appropriate concentration of CART could suppress the apoptosis of OGD NSCs. Finally, Western blotting was conducted to examine the CREB pathway and related protein expression after treatment with KG-501, revealing that an appropriate concentration of CART regulated both apoptosis and proliferation in OGD NSCs through CREB signaling., Conclusion: The concentration of CART at 0.8 nM may be deemed appropriate for inhibiting apoptosis and promoting proliferation in OGD NSCs in vitro . The mechanism maybe through activating the CREB pathway., 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 Zhang, Chen, Zou, Shu, Zhang, He, Su, Wang, Wang and Sha.)

Aim: Angiogenesis is a key event in the successful healing of pulp injuries, and hypoxia is the main stimulator of pulpal angiogenesis. In this study, we investigated the effect of hypoxia on the proangiogenic potential of human dental pulp stem cells (hDPSCs) and the role of miR-143-5p in the process., Methodology: Human dental pulp stem cells were isolated, cultured and characterized in vitro. Cobalt chloride (CoCl 2 ) was used to induce hypoxia in hDPSCs. CCK-8 and Transwell assays were used to determine the effect of hypoxia on hDPSCs proliferation and migration. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting (WB) and ELISA were performed to assess the mRNA and protein levels of HIF-1α and angiogenic cytokines in hDPSCs. The effect of hypoxia on hDPSCs proangiogenic potential was measured in vitro using Matrigel tube formation and chick chorioallantoic membrane (CAM) assays. Recombinant lentiviral vectors were constructed to stably overexpress or inhibit miR-143-5p in hDPSCs, and the proangiogenic effects were assessed using qRT-PCR, WB, and tube formation assays. miR-143-5p target genes were identified and verified using bioinformatics prediction tools, dual-luciferase reporter assays and RNA pull-down experiments. Finally, a subcutaneous transplantation model in nude mice was used to determine the effects of hypoxia treatment and miR-143-5p overexpression/inhibition in hDPSCs in dental pulp regeneration., Results: Hypoxia promotes hDPSCs proliferation, migration and proangiogenic potential. The in vivo experiments showed that hypoxia treatment (50 and 100 μM CoCl 2 ) promoted pulp angiogenesis and dentine formation. In contrast to the levels of proangiogenic factors, miR-143-5p levels decreased with increasing CoCl 2 concentration. miR-143-5p inhibition significantly promoted proangiogenic potential of hDPSCs, whereas miR-143-5p overexpression inhibited angiogenesis in vitro. Dual-luciferase reporter assay identified retinoic acid receptor-related orphan receptor alpha (RORA) as an miR-143-5p target gene in hDPSCs. RNA pull-down experiments demonstrated that HIF-1α and RORA were pulled down by biotin-labelled miR-143-5p, and the levels of HIF-1α and RORA bound to miR-143-5p in the hypoxia group were lower than those in the normoxia group. Inhibition of miR-143-5p expression in hDPSCs promoted ectopic dental pulp tissue regeneration., Conclusions: CoCl 2 -induced hypoxia promotes hDPSCs-driven paracrine angiogenesis and pulp regeneration. The inhibition of miR-143-5p upregulates the proangiogenic potential of hDPSCs under hypoxic conditions by directly targeting HIF-1α and RORA., (© 2024 British Endodontic Society. Published by John Wiley & Sons Ltd.)

Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life. Many stroke victims are left with long-term neurological dysfunction, which adversely affects the well-being of the individual and the broader socioeconomic impact. Currently, post-stroke brain dysfunction is a major and difficult area of treatment. Vagus nerve stimulation is a Food and Drug Administration-approved exploratory treatment option for autism, refractory depression, epilepsy, and Alzheimer's disease. It is expected to be a novel therapeutic technique for the treatment of stroke owing to its association with multiple mechanisms such as altering neurotransmitters and the plasticity of central neurons. In animal models of acute ischemic stroke, vagus nerve stimulation has been shown to reduce infarct size, reduce post-stroke neurological damage, and improve learning and memory capacity in rats with stroke by reducing the inflammatory response, regulating blood-brain barrier permeability, and promoting angiogenesis and neurogenesis. At present, vagus nerve stimulation includes both invasive and non-invasive vagus nerve stimulation. Clinical studies have found that invasive vagus nerve stimulation combined with rehabilitation therapy is effective in improving upper limb motor and cognitive abilities in stroke patients. Further clinical studies have shown that non-invasive vagus nerve stimulation, including ear/cervical vagus nerve stimulation, can stimulate vagal projections to the central nervous system similarly to invasive vagus nerve stimulation and can have the same effect. In this paper, we first describe the multiple effects of vagus nerve stimulation in stroke, and then discuss in depth its neuroprotective mechanisms in ischemic stroke. We go on to outline the results of the current major clinical applications of invasive and non-invasive vagus nerve stimulation. Finally, we provide a more comprehensive evaluation of the advantages and disadvantages of different types of vagus nerve stimulation in the treatment of cerebral ischemia and provide an outlook on the developmental trends. We believe that vagus nerve stimulation, as an effective treatment for stroke, will be widely used in clinical practice to promote the recovery of stroke patients and reduce the incidence of disability., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

Improving the activity of uricase and lowering its immunogenicity remain significant challenges in the enzyme replacement management of hyperuricemia and related inflammatory diseases. Herein, an immunogenicity-masking strategy based on engineered red blood cells (RBCs) was developed for effective uricase delivery against both hyperuricemia and gout. The dynamic membrane of RBCs enabled high resistance to protease inactivation and hydrogen peroxide accumulation. Benefiting from these advantages, a single infusion of RBC-loaded uricase (Uri@RBC) performed prolonged blood circulation and sustained hyperuricemia management. Importantly, RBCs masked the immunogenicity of uricase, leading to the maintenance of UA-lowering performance after repeated infusion through reduced antibody-mediated macrophage clearance. In an acute gout model, Uri@RBC profoundly alleviated joint edema and inflammation with minimal systemic toxicity. This study supports the employment of immunogenicity-masking tools for efficient and safe enzyme delivery, and this strategy may be leveraged to improve the usefulness of enzyme replacement therapies for managing a wide range of inflammatory diseases., Competing Interests: Declaration of competing interest These authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Patients with Chronic Obstructive Pulmonary Disease (COPD) frequently face substantial medication burdens. Follow-up care on medication management is critical in achieving disease control. This study aimed to analyze the complexity of COPD-specific medication and determine how it impacted patients' attendance on follow-up care., Methods: This multicenter study includes patients with COPD from 1,223 hospitals across 29 provinces in China from January 2021 to November 2022. The medication Regimen Complexity Index (MRCI) score was used to measure COPD-specific medication complexity. The association between medication complexity and follow-up care attendance was evaluated using the Cox Proportional Hazard Model., Results: Among 16,684 patients, only 2,306 (13.8%) returned for follow-up medication management. 20.3% of the patients had high complex medication regimen (MRCI score >15.0). The analysis revealed that compared to those with less complex regimens, patients with more complex medication regimens were significantly less likely to attend the follow-up medication care, with a Hazard Ratio (HR) of 0.82 (95% Confidence Interval [CI], 0.74-0.91). Specifically, patients with more complex dosage forms were 51% less likely to attend the follow-up care (95% CI, 0.43-0.57). This pattern was especially marked among male patients, patients younger than 65 years, and those without comorbid conditions., Conclusion: Higher medication complexity was associated with a decreased likelihood of attending follow-up care. To promote care continuity in chronic disease management, individuals with complex medication regimens should be prioritized for enhanced education. Furthermore, pharmacists collaborating with respiratory physicians to deprescribe and simplify dosage forms should be considered in the disease management process., 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. The handling editor ZCG declared a shared parent affiliation with the author XH at the time of review., (Copyright © 2024 Ma, Wang, Chen, Lian, Zhao, He, Qiu, Han, Liu and Wang.)

Accurate aircraft turnaround time prediction is an important way to coordinate the operation time of airport ground service and improve the efficiency of airport operation. In this paper, by analyzing the aircraft turnaround operation process, a description model based on Time Transition Petri Net is proposed. The model describes the flight turnaround operation process and the logical relationship of the operation. According to the model, a dynamic prediction method of turnaround time based on Bayesian theorem is designed. According to the actual landing time of the flight, the aircraft turnaround time is predicted. The specific method is to obtain the prior probability distribution and joint distribution law of each operation link according to the flight history data, and use Shapiro-Wilke to test the prior probability distribution of each link. Based on the analysis and comparison between the actual turnaround data of a large airport in China and the forecast data proposed in this paper, the root-mean-square error 3.75 minutes and the mean absolute error 3.40 minutes can be calculated. This paper contributes to the improvement of flight punctuality rate and airport clearance level., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cui 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.)

The design and development of organic solid-state luminescent materials stand as crucial pillars within the realm of contemporary photofunctional materials. Overcoming challenges such as concentration quenching and achieving tailored luminescent properties necessitates a judicious approach to molecular structure design and the strategic utilization of diverse stimuli to modulate molecular packing patterns. Among the myriad candidates, α-cyanodiarylethenes (CAEs) emerge with distinctive solid-state luminescent attributes, capable of forming self-assembled packing structures with varying degrees of π-π stacking. This characteristic endows them with potential in the field of intelligent molecular responsive materials and optoelectronic devices. This tutorial review embarks on an exploration of design strategies geared towards attaining tunable solid-state emission through customized packing of CAEs. It explores the utilization of stimuli responses, including such as mechanical forces, light irradiation, solvent interactions, thermal influences, as well as the utilization of co-assembly methodologies. The overarching aim of this review is to provide a widely applicable platform fostering the flourishing development of modern organic photofunctional materials through integrating principles of molecular engineering, organic optoelectronics, and materials science.

Due to matching biomechanical properties and significant biological activity, Mg-based implants present great potential in orthopedic applications. In recent years, the biocompatibility and therapeutic effect of magnesium-based implants have been widely investigated in trauma repair. In contrast, the R&D work of Mg-based implants in spinal fusion is still limited. This review firstly introduced the general background for Mg-based implants. Secondly, the mechanical properties and degradation behaviors of Mg and its traditional and novel alloys were reviewed. Then, different surface modification techniques of Mg-based implants were described. Thirdly, this review comprehensively summarized the biological pathways of Mg degradation to promote bone formation in neuro-musculoskeletal circuit, angiogenesis with H-type vessel formation, osteogenesis with osteoblasts activation and chondrocyte ossification as an integrated system. Fourthly, this review followed the translation process of Mg-based implants via updating the preclinical studies in fracture fixation, sports trauma repair and reconstruction, and bone distraction for large bone defect. Furthermore, the pilot clinical studies were involved to demonstrate the reliable clinical safety and satisfactory bioactive effects of Mg-based implants in bone formation. Finally, this review introduced the background of spine fusion surgeryand the challenges of biological matching cage development. At last, this review prospected the translation potential of a hybrid Mg-PEEK spine fusion cage design., Competing Interests: This study was supported by 10.13039/501100009592Beijing Municipal Science and Technology Project (Z201100005520073), Key Clinical projects of Peking University Third hospital (BYSY2022064), 10.13039/501100002858China Postdoctoral Science Foundation (M2023740146), and 10.13039/501100001809National Natural Science Foundation of China (82302731). Yufeng Zheng is editor-in-chief for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2024 The Authors.)

To study the characteristics of nasal airflow in the presence of nasal cycle by computational fluid dynamics. CT scan data of a healthy Chinese individual was used to construct a three-dimensional model of the nasal cavity to be used as simulation domain. A sinusoidal airflow velocity is set at the nasal cavity entrance to reproduce the breathing pattern of a healthy human. There was a significant difference in the cross-sectional area between the two sides of the nasal cavity. Particularly, the decongested side is characterized by a larger cross-section area, and consequently, by a larger volume with respect to the congested side. The airflow velocity, pressure, and nasal resistance were higher on the congested narrow side. The temperature regulation ability on the congested narrow side was stronger than that on the decongested wider side. During the nasal cycle, there are differences in the nasal cavity function between the congested and decongested sides. Therefore, when evaluating the impact of various factors on nasal cavity function, the nasal cycle should be considered., (© 2024. The Author(s).)

Metastasis is one of the key factors of treatment failure in late-stage colorectal cancer (CRC). Metastatic CRC frequently develops resistance to chemotherapeutic agents. This study aimed to identify the novel regulators from "hidden" proteins encoded by long noncoding RNAs (lncRNAs) involved in tumor metastasis and chemoresistance. Methods: CRISPR/Cas9 library functional screening was employed to identify the critical suppressor of cancer metastasis in highly invasive CRC models. Western blotting, immunofluorescence staining, invasion, migration, wound healing, WST-1, colony formation, gain- and loss-of-function experiments, in vivo experimental metastasis models, multiplex immunohistochemical staining, immunohistochemistry, qRT-PCR, and RT-PCR were used to assess the functional and clinical significance of FOXP3, PRDM16-DT, HNRNPA2B1, and L- CHEK2 . RNA-sequencing, co-immunoprecipitation, qRT-PCR, RT-PCR, RNA affinity purification, RNA immunoprecipitation, MeRIP-quantitative PCR, fluorescence in situ hybridization, chromatin immunoprecipitation and luciferase reporter assay were performed to gain mechanistic insights into the role of PRDM16-DT in cancer metastasis and chemoresistance. An oxaliplatin-resistant CRC cell line was established by in vivo selection. WST-1, colony formation, invasion, migration, Biacore technology, gain- and loss-of-function experiments and an in vivo experimental metastasis model were used to determine the function and mechanism of cimicifugoside H-1 in CRC. Results: The novel protein PRDM16-DT, encoded by LINC00982, was identified as a cancer metastasis and chemoresistance suppressor. The down-regulated level of PRDM16-DT was positively associated with malignant phenotypes and poor prognosis of CRC patients. Transcriptionally regulated by FOXP3, PRDM16-DT directly interacted with HNRNPA2B1 and competitively decreased HNRNPA2B1 binding to exon 9 of CHEK2 , resulting in the formation of long CHEK2 (L- CHEK2 ), subsequently promoting E-cadherin secretion. PRDM16-DT-induced E-cadherin secretion inhibited fibroblast activation, which in turn suppressed CRC metastasis by decreasing MMP9 secretion. Cimicifugoside H-1, a natural compound, can bind to LEU89, HIS91, and LEU92 of FOXP3 and significantly upregulated PRDM16-DT expression to repress CRC metastasis and reverse oxaliplatin resistance. Conclusions: lncRNA LINC00982 can express a new protein PRDM16-DT to function as a novel regulator in cancer metastasis and drug resistance of CRC. Cimicifugoside H-1 can act on the upstream of the PRDM16-DT signaling pathway to alleviate cancer chemoresistance., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Chlorogenic acid (CGA) is an effective phenolic antioxidant that can scavenge hydroxyl radicals and superoxide anions. Herein, the protective effects and mechanisms leading to CGA-induced porcine parthenogenetic activation (PA) in early-stage embryos were investigated. Our results showed that 50 μM CGA treatment during the in vitro culture (IVC) period significantly increased the cleavage and blastocyst formation rates and improved the blastocyst quality of porcine early-stage embryos derived from PAs. Then, genes related to zygotic genome activation (ZGA) were identified and investigated, revealing that CGA can promote ZGA in porcine PA early-stage embryos. Further analysis revealed that CGA treatment during the IVC period decreased the abundance of reactive oxygen species (ROS), increased the abundance of glutathione and enhanced the activity of catalase and superoxide dismutase in porcine PA early-stage embryos. Mitochondrial function analysis revealed that CGA increased mitochondrial membrane potential and ATP levels and upregulated the mitochondrial homeostasis-related gene NRF-1 in porcine PA early-stage embryos. In summary, our results suggest that CGA treatment during the IVC period helps porcine PA early-stage embryos by regulating oxidative stress and improving mitochondrial function., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

The cell nucleus serves as the pivotal command center of living cells, and delivering therapeutic agents directly into the nucleus can result in highly efficient anti-tumor eradication of cancer cells. However, nucleus-targeting drug delivery is very difficult due to the presence of numerous biological barriers. Here, three antitumor drugs (DNase I, ICG: indocyanine green, and THP: pirarubicin) were sequentially triggered protein self-assembly to produce a nucleus-targeting and programmed responsive multi-drugs delivery system (DIT). DIT consisted of uniform spherical particles with a size of 282 ± 7.7 nm. The acidic microenvironment of tumors and near-infrared light could successively trigger DIT for the programmed release of three drugs, enabling targeted delivery to the tumor. THP served as a nucleus-guiding molecule and a chemotherapy drug. Through THP-guided DIT, DNase I was successfully delivered to the nucleus of tumor cells and killed them by degrading their DNA. Tumor acidic microenvironment had the ability to induce DIT, leading to the aggregation of sufficient ICG in the tumor tissues. This provided an opportunity for the photothermal therapy of ICG. Hence, three drugs were cleverly combined using a simple method to achieve multi-drugs targeted delivery and highly effective combined anticancer therapy., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chemical recycling is a promising approach to reduce plastic pollution. Timely and accurate size analysis of produced nanoplastics is necessary to monitor the process and assess the quality of chemical recycling. In this work, a sandwich-type microelectrode sensor was developed for the size assessment of nanoplastics. β-Mercaptoethylamine was modified on the microelectrode to enhance its surface positive charge density. Polystyrene (PS) nanoplastics were captured on the sensor through electrostatic interactions. Ferrocene was used as an electrochemical beacon and attached to PS via hydrophobic interactions. The results show a nonlinear dependence of the sensor's current response on the PS particle size. The size resolving ability of the microelectrode is mainly attributed to the small size of the electrode and the resulting attenuation of the electric field strength. For mixed samples with different particle sizes, this method can provide accurate average particle sizes. Through an effective pretreatment process, the method can be applied to PS nanoplastics with different surface properties, ensuring its application in evaluating different chemical recycling methods.

Some patients with heatstroke also experience intracerebral hemorrhage (ICH). However, clinical case reports of heatstroke-induced ICH are rare. The risk factors for cerebral hemorrhage after heatstroke remain unknown. The present study evaluated the clinical characteristics and risk factors of patients with heatstroke-related ICH. In this retrospective observational study, we collected data on all ICHs after heatstroke occurred between 2012 and 2022. The characteristics of patients with heatstroke-induced ICH were described. The risk factors for cerebral hemorrhage after heatstroke were examined using logistic regression analysis. In total, 177 patients were included in this study, and 11 patients with ICH secondary to heatstroke were identified. Variables with P values of <.05 in univariate models, comparing the cerebral hemorrhage and control groups, included heatstroke cause, temperature, heart rate, respiratory rate, vasopressor use, mechanical ventilation use, Acute Physiology and Chronic Health Evaluation II, total bilirubin, creatinine, platelet count, prothrombin time, procalcitonin, creatine kinase, disseminated intravascular coagulation (DIC) occurrence, and DIC score. Multivariate logistic regression showed that heatstroke patients with higher DIC scores (odds ratio, 18.402, 95% confidence interval, 1.384-244.763, P = .027) and higher creatine kinase levels (odds ratio, 1.021, 95% confidence interval, 1.002-1.041, P = .033) were at a higher risk of developing ICH. The death rate was higher in the cerebral hemorrhage group than in the control group (P = .042). Heatstroke-related cerebral hemorrhage may be associated with elevated creatinine levels and DIC severity (International Society on Thrombosis and Hemostasis score) after heatstroke, and heatstroke with cerebral hemorrhage may accelerate death., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Elevated bone resorption and diminished bone formation have been recognized as the primary features of glucocorticoid-associated skeletal disorders. However, the direct effects of excess glucocorticoids on bone turnover remain unclear. Here, we explored the outcomes of exogenous glucocorticoid treatment on bone loss and delayed fracture healing in mice and found that reduced bone turnover was a dominant feature, resulting in a net loss of bone mass. The primary effect of glucocorticoids on osteogenic differentiation was not inhibitory; instead, they cooperated with macrophages to facilitate osteogenesis. Impaired local nutrient status - notably, obstructed fatty acid transportation - was a key factor contributing to glucocorticoid-induced impairment of bone turnover in vivo. Furthermore, fatty acid oxidation in macrophages fueled the ability of glucocorticoid-liganded receptors to enter the nucleus and then promoted the expression of BMP2, a key cytokine that facilitates osteogenesis. Metabolic reprogramming by localized fatty acid delivery partly rescued glucocorticoid-induced pathology by restoring a healthier immune-metabolic milieu. These data provide insights into the multifactorial metabolic mechanisms by which glucocorticoids generate skeletal disorders, thus suggesting possible therapeutic avenues.

High fluorescence background poses a substantial challenge to surface-enhanced Raman scattering (SERS), thereby limiting its broader applicability across diverse domains. In this work, silver nanoparticle (Ag NP)-loaded graphene oxide aerogel nanomaterials (GO-Ag ANM) were prepared for sensitive SERS detection of fluorescent explosive 2,4,8,10-tetranitrobenzo-1,3 a ,6,6 a -tetraazapentaenopyridine (BPTAP) by a fluorescence quenching strategy. By harnessing the fluorescence quenching properties of graphene and the localized surface plasmon resonance of silver nanoparticles, the synthesized aerogels exhibited effective fluorescence quenching and Raman enhancement capabilities when employed for BPTAP analysis with 532 nm laser excitation. Significantly, precise control over the loading quantity of silver nanoparticles (Ag NPs) resulted in the remarkable sensitivity of the surface-enhanced Raman scattering (SERS) effect. This method allowed for the detection of fluorescent explosive BPTAP at an extraordinarily low concentration of 1 × 10 -7 M. Furthermore, the approach also demonstrated excellent detection capabilities for the dyes R6G, CV, and RhB. This study offers valuable insights for the sensitive detection of fluorescent molecules.

The aim of this article is to introduce the roles and mechanisms of the JAK2/STAT3 pathway in various cardiovascular diseases, such as myocardial fibrosis, cardiac hypertrophy, atherosclerosis, myocardial infarction, and myocardial ischemiareperfusion. In addition, the effects of phytochemical ingredients and different natural plants, mainly traditional Chinese medicines, on the regulation of different cardiovascular diseases via the JAK2/STAT3 pathway are discussed. Surprisingly, the JAK2 pathway has dual roles in different cardiovascular diseases. Future research should focus on the dual regulatory effects of different phytochemical ingredients and natural plants on JAK2 to pave the way for their use in clinical trials., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest that pertain to this work. This work described has not been published previously (except in the form of an abstract, a published lecture or academic thesis, see’Multiple, redundant or concurrent publication’ for more information), that it is not under consideration for publication elsewhere, that its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This research intended to investigate the influence of the operation of both kinds of hysterectomies in the risk of wound infection and the degree of wound dehiscence. Both of them were open field and laparoscope. In this research, we looked into four databases: PubMed, Web of Science, Embase and Cochrane Library. Research was conducted on various operative methods for hysterectomy in obese patients between 2000 and October 2023. Two independent investigators performed an independent review of the data, established the inclusion and exclusion criteria, and managed the results with Endnote software. It also evaluated the quality of the included literature. Finally, the data were analysed with RevMan 5.3. This study involved 874 cases, 387 cases received laparoscopy and 487 cases received open access operation. Our findings indicate that there is a significant reduction in the rate of post-operative wound infection among those who have received laparoscopy compared with who have received open surgical procedures (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.01-0.15; p < 0.001); There was no statistical difference between the rate of post-operative wound dehiscence and those who received laparotomy compared with those who received open surgical procedures (OR, 0.33; 95% CI, 0.10-1.11; p = 0.07); The estimated amount of blood lost during the operation was less in the laparoscopy group compared with the open procedure (mean difference, -123.72; 95% CI, -215.16 to -32.28; p = 0.008). Generally speaking, the application of laparoscopy to overweight women who have had a hysterectomy results in a reduction in the expected amount of bleeding during surgery and a reduction in the risk of post-operative wound infections., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Despite the many studies carried out over the past decade to determine the biodegradation performance of magnesium and its alloys, few studies focused on the effect of altered surface area to volume ratio on in vitro and in vivo degradation rate and osteogenesis. Here, high purity magnesium cylindrical rods with gradient of surface area to volume ratio were processed by excavating different numbers of grooves on the side surface. The immersion test in SBF solution and the rat femoral condylar bone defect model were used to evaluate the degradation of magnesium rods in vitro and in vivo , respectively. We demonstrated that, the increased number of grooves on the HP magnesium surface represented a decrease in the percentage of residual volume over time, not necessarily an increase in absolute degradation volume or a regular change in corrosion rate. Furthermore, there were strong linear correlations between the relative degradation volume and the initial surface-to-volume ratio of HP magnesium rods both in vitro and in vivo . The difference in the slope of this relationship in vitro and in vivo might help to determine the possible range of in vivo degradation rates via in vitro data. In addition, the corrosion rate is more suitable for evaluating bone formation surrounding the different HP magnesium rods. Our findings in this work may facilitate adjusting the in vivo degradation and osteogenesis of different kinds of orthopedic implants made of the same magnesium-based material, and thus, accelerate the clinical popularization and application., Competing Interests: There is no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Background: The optimal multimorbidity measures for predicting disability trajectories are not universally agreed upon. We developed a multimorbidity index among middle-aged and older community-dwelling Chinese adults and compare its predictive ability of disability trajectories with other multimorbidity measures., Methods: This study included 17,649 participants aged ≥50 years from the China Health and Retirement Longitudinal Survey 2011-2018. Two disability trajectory groups were estimated using the total disability score differences calculated between each follow-up visit and baseline. A weighted index was constructed using logistic regression models for disability trajectories based on the training set (70 %). The index and the condition count were used, along with the pattern identified by the latent class analysis to measure multimorbidity at baseline. Logistic regression models were used in the training set to examine associations between each multimorbidity measure and disability trajectories. C-statistics, integrated discrimination improvements, and net reclassification indices were applied to compare the performance of different multimorbidity measures in predicting disability trajectories in the testing set (30 %)., Results: In the newly developed multimorbidity index, the weights of the chronic conditions varied from 1.04 to 2.55. The multimorbidity index had a higher predictive performance than the condition count. The condition count performed better than the multimorbidity pattern in predicting disability trajectories., Limitation: Self-reported chronic conditions., Conclusions: The multimorbidity index may be considered an ideal measurement in predicting disability trajectories among middle-aged and older community-dwelling Chinese adults. The condition count is also suggested due to its simplicity and superior predictive performance., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ferroptosis suppressor protein 1 (FSP1) is a glutathione-independent ferroptosis inhibitory factor. FSP1 has been found to play a crucial role in the regulation of mitochondrial function and ferroptosis. However, its function in porcine early embryonic development remains unknown. In the present research, we found that FSP1 was expressed at different stages during porcine early embryo development. Compared with the control condition, inhibition of FSP1 reduced the cleavage rate at 24 h and 48 h and the blastocyst rate at 144 h. In addition, inhibiting FSP1 reduced the blastocyst diameter, total cell number, and proliferation capacity. Further analysis showed that inhibition of FSP1 significantly increased the levels of ferrous ions (Fe 2+ ) and MDA but not GPX4. We also found that inhibition of FSP1 significantly decreased mitochondrial membrane potential and ATP levels, which in turn caused excessive accumulation of ROS and decreased the levels of GSH and the activity of the intracellular antioxidant enzymes SOD and CAT in embryos. In conclusion, FSP1, an important regulator, participates in regulating the development and quality of porcine early embryos. Inhibition of FSP1 impairs blastocyst formation, induces glutathione-independent ferroptosis, and further leads to oxidative stress due to mitochondrial dysfunction, ultimately affecting the developmental competence and impairing the quality of porcine early embryos., (Copyright © 2023 Elsevier Inc. All rights reserved.)

RNA interference (RNAi) presents great potential against intractable liver diseases. However, the establishment of specific, efficient, and safe delivery systems targeting hepatocytes remains a great challenge. Herein, we described a promising hepatocytes-targeting system through integrating triantennary N-acetylgalactosamine (GalNAc)-engineered cell membrane with biodegradable mesoporous silica nanoparticles, which efficiently and safely delivered siRNA to hepatocytes and silenced the target PCSK9 gene expression for the treatment of non-alcoholic fatty liver disease. Having optimized the GalNAc-engineering strategy, insertion orders, and cell membrane source, we obtained the best-performing GalNAc-formulations allowing strong hepatocyte-specific internalization with reduced Kupffer cell capture, resulting in robust gene silencing and less hepatotoxicity when compared with cationic lipid-based GalNAc-formulations. Consequently, a durable reduction of lipid accumulation and damage was achieved by systemic administering siRNAs targeting PCSK9 in high-fat diet-fed mice, accompanied by displaying desirable safety profiles. Taken together, this GalNAc-engineering biomimetics represented versatile, efficient, and safe carriers for the development of hepatocyte-specific gene therapeutics, and prevention of metabolic diseases. STATEMENT OF SIGNIFICANCE: Compared to MSN@LP-GN3 (MC3-LNP), MSN@CM-GN3 exhibited strong hepatocyte targeting and Kupffer cell escaping, as well as good biocompatibility for safe and efficient siRNA delivery. Furthermore, siPCSK9 delivered by MSN@CM-GN3 reduced both serum and liver LDL-C, TG, TC levels and lipid droplets in HFD-induced mice, resulting in better performance than MSN/siPCSK9@LP-GN3 in terms of lipid-lowering effect and safety profiles. These findings indicated promising advantages of our biomimetic GN3-based systems for hepatocyte-specific gene delivery in chronic liver diseases. Our work addressed the challenges associated with the lower targeting efficiency of cell membrane-mimetic drug delivery systems and the immunogenicity of traditional GalNAc delivery systems. In conclusion, this study provided an effective and versatile approach for efficient and safe gene editing using ligand-integrated biomimetic nanoplatforms., Competing Interests: Declaration of Competing Interest These authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Dyslipidemia is frequently exhibited in individuals with chronic kidney disease (CKD). Remnant cholesterol (RC), an emerging novel lipid marker, plays an elusive role in CKD progression. This study sought to investigate the association of RC with decreased kidney function or albuminuria in the general population of U.S., Method: Data were retrieved from the continuous 2001 to 2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Individuals aged between 18 and 70 years were included. RC was divided into quartiles. Albuminuria was defined by albumin-to-creatinine ratio (ACR) ≥30 mg/g, while reduced kidney function was described as an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m 2 . Using a multivariable regression model, the association of RC with decreased eGFR or albuminuria was examined. The dose‒response relationship between RC and eGFR or ACR was also investigated using a restricted cubic spline (RCS) model., Results: A total of 1551 (10.98%) participants with impaired renal function or albuminuria were identified. After multivariate adjustment, RC was not significantly associated with kidney function decline or albuminuria (odds ratio (OR) 1.24, 95% confidence interval (95% CI): 0.95, 1.61). However, a significantly inverse correlation was observed between RC and eGFR in a dose‒response manner (β -2.12, 95% CI: -3.04, -1.21). This association remained consistent when stratifying data by gender, age, race, hypertension, diabetes and body mass index (BMI)., Conclusion: A higher RC was significantly correlated with a lower eGFR in the general population. The role of RC in predicting kidney outcomes needed further investigation in prospective studies., (© 2023. The Author(s).)

Interactive image segmentation (IIS) has been widely used in various fields, such as medicine, industry, etc. However, some core issues, such as pixel imbalance, remain unresolved so far. Different from existing methods based on pre-processing or post-processing, we analyze the cause of pixel imbalance in depth from the two perspectives of pixel number and pixel difficulty. Based on this, a novel and unified Click-pixel Cognition Fusion network with Balanced Cut (CCF-BC) is proposed in this paper. On the one hand, the Click-pixel Cognition Fusion (CCF) module, inspired by the human cognition mechanism, is designed to increase the number of click-related pixels (namely, positive pixels) being correctly segmented, where the click and visual information are fully fused by using a progressive three-tier interaction strategy. On the other hand, a general loss, Balanced Normalized Focal Loss (BNFL), is proposed. Its core is to use a group of control coefficients related to sample gradients and forces the network to pay more attention to positive and hard-to-segment pixels during training. As a result, BNFL always tends to obtain a balanced cut of positive and negative samples in the decision space. Theoretical analysis shows that the commonly used Focal and BCE losses can be regarded as special cases of BNFL. Experiment results of five well-recognized datasets have shown the superiority of the proposed CCF-BC method compared to other state-of-the-art methods. The source code is publicly available at https://github.com/lab206/CCF-BC.

Background and Objective: Remimazolam is a water-soluble sedative-anesthetic with short-acting properties and less hemodynamic effects. Currently, it is primarily used for gastroenteroscopy sedation., Aim: The aim of this study is to investigate the effectiveness and safety of Remimazolam as an alternative intravenous anesthetic agent in surgical patients, in order to expand clinical options beyond Propofol., Methods: Eighty patients aged 20-69 and classified as an American Society of Anesthesiologists physical status I-II were randomly assigned to either the Remimazolam group (RM group) or the Propofol group (PR group) for anesthesia induction and maintenance. Hemodynamics and Bispectral Index (BIS) were recorded before and after anesthesia, along with other relevant indices such as the time, to loss of consciousness (LoC), operation time, anesthesia time, awakening time, the number of cases of injection site pain. Additionally, the Ramsay sedation score, intraoperative awareness, dreaming, and postoperative adverse events were also assessed., Results: After anesthesia, both groups experienced a significant decrease in blood pressure compared to baseline values, however, the reduction in blood pressure was less significant in the RM group than in the PR group (P<0.05). The heart rate of patients in the RM group remained relatively stable at all time points. There were significantly more cases of injection site pain and use of pressor or atropine during operation observed in the PR group compared to the RM group (P<0.05). There were no significant differences between the two groups in terms of time to loss of consciousness, anesthesia time, operation time, awakening time, and intraoperative awareness (P>0.05). However, at 5 and 30 minutes after awakening, the Ramsay sedation score was significantly better in the RM group compared to the PR group (P<0.05)., Conclusion: When remimazolam is used for intravenous anesthesia induction and maintenance, it can achieve a favorable anesthetic effect while maintaining a relatively stable blood pressure and heart rate. Patients experience shorter awakening times (8.3±3.7 min), better awakening quality (5 min Ramsay sedation score is 2 points), and no intraoperative awareness., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Interfacial charge transfer resistance is one of the main limiting factors for realizing high photocatalytic efficiency of heterostructures system. Herein, an activated carbon layer is successfully introduced between the interface of polymer carbon nitride (CN) and TiO 2 heterostructure (CNP-x) as charge transfer medium by in situ pyrolysis carbonization method. Because of the lower spatial resistance of the crystalline/amorphous interface and the fast carrier transportation character of activated carbon, the efficiency of TiO 2 in extracting photoinduced electrons from CN was significantly improved. That is, the separation/transport of photocarriers in CNP-x heterostructure is accelerated, and the recombination time of photogenerated electrons and holes is prolonged. The CNP-1 exhibits a H 2 evolution rate of 1298.5 μmol h -1 with apparent quantum yield (AQY) of 34.5 %, 20.3 % and 12.6 % at 365 nm, 380 nm and 400 nm, respectively. This work offers a novel and unique strategy to promote interface charge separation and transport of CN-based heterostructures by accurately introduction charge transfer medium., 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 © 2023 Elsevier Inc. All rights reserved.)

Background: Reactive cutaneous capillary endothelial proliferation (RCCEP) is a common immune-related adverse event (irAE) related to camrelizumab. This study aimed to investigate the risk factors of RCCEP and its association with patients' survival., Methods: This retrospective study collected the data of consecutive patients with non-small cell lung cancer (NSCLC) who received camrelizumab between January 2019 and December 2021. Baseline characteristics and peripheral blood biomarkers were collected. The outcomes were the occurrence of RCCEP and progression-free survival (PFS). The factors associated with RCCEP were analyzed using univariable and multivariable logistic regression. The association between PFS and RCCEP occurrence was analyzed by the log-rank test., Results: Among the 80 patients included, 24 (30.0%) developed RCCEP, and 56 did not. Among the patients with RCCEP, only four reported the occurrence of grade 3-4 RCCEP. The multivariable analysis revealed that a percentage of eosinophil (EOS%) >1.75% was significantly associated with a higher risk of RCCEP [odds ratio (OR) =4.484; 95% confidence interval (CI): 1.139-17.651] and camrelizumab combined with an anti-angiogenic agent was significantly associated with a lower risk of RCCEP (OR =0.188; 95% CI: 0.055-0.639). The median PFS was numerically longer in patients with RCCEP than in those who did not (17 vs. 9 months, P=0.069). Patients who had baseline EOS% >1.75% and received camrelizumab without an anti-angiogenic agent had a longer median PFS than those who did not (17 vs. 9 months, P=0.011)., Conclusions: Baseline EOS% >1.75% and camrelizumab without an anti-angiogenic agent were risk factors of RCCEP and might be associated with better survival in patients with NSCLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1144/coif). X.B. reports funding from the Bethune Charitable Foundation Pharmaceutical Research Capacity Building Project (No. Z04JKM2021005) and the Clinical Pharmacy Innovation Institute, Shanghai Jiao Tong University School of Medicine (No. CXYJY2019MS004). The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Creating new insecticide lead compounds based on the design and modification of natural products is a novel process, of which chlorfenapyr is a typical successful example. Chlorfenapyr is an arylpyrrole derivative that has high biological activity, a wide insecticidal spectrum, and a unique mode of action. For decades, a series of chlorfenapyr derivatives were designed and synthesized continuously, of which many highly active insecticidal compounds were discovered sequentially. However, due to the widespread application of chlorfenapyr and its degradation properties, some adverse effects, including pest resistance and environmental toxicity, occurred. In this review, a brief history of the discovery and development of chlorfenapyr is first introduced. Then, the synthesis, structural modification, structure activity relationship, and action mechanism of arylpyrroles are summarized. However, challenges and limitations still exist, especially in regard to the connection with pest resistance and environmental toxicology, which is discussed at the end of this review. This comprehensive summary of chlorfenapyr further promotes its progress and sensible application for pest management.

Flavonoids are a highly abundant class of secondary metabolites present in plants. Isoflavonoids, in particular, are primarily synthesized in leguminous plants within the subfamily Papilionoideae. Numerous reports have established the favorable role of isoflavonoids in preventing a range of human diseases. Among the isoflavonoid components, glyceollins are synthesized specifically in soybean plants and have displayed promising effects in mitigating the occurrence and progression of breast and ovarian cancers as well as other diseases. Consequently, glyceollins have become a sought-after natural component for promoting women's health. In recent years, extensive research has focused on investigating the molecular mechanism underlying the preventative properties of glyceollins against various diseases. Substantial progress has also been made toward elucidating the biosynthetic pathway of glyceollins and exploring potential regulatory factors. Herein, we provide a review of the research conducted on glyceollins since their discovery five decades ago (1972-2023). We summarize their pharmacological effects, biosynthetic pathways, and advancements in chemical synthesis to enhance our understanding of the molecular mechanisms of their function and the genes involved in their biosynthetic pathway. Such knowledge may facilitate improved glyceollin synthesis and the creation of health products based on glyceollins., 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., (© 2023 The Authors.)

Since the linkages structured in covalent organic frameworks (COFs) usually impact the charge transfer behavior during photocatalytic hydrogen evolution reaction (pc-HER), linkage dependence on charge transfer kinetics should be further claimed. Herein, COFs with N-based linkages and pyrene-based building nodes are constructed to enable us to obtain new clues about the charge transfer behavior and evolution tendency relevant to linkages at a molecular level for pc-HER. It is demonstrated that photo-excited electrons preferably move to the N sites in C=N linkage for pc-HER and are trapped around NN linkage as well. A high electron transfer rate does not point to high photocatalytic activity directly, while a small difference between the electron transfer rate and electron recombination rate Δk CT - CR predicts the inefficiency of charge transfer in Azod-COFs. Contrarily, large value of Δk CT - CR in the case of Benzd-COFs, demonstrats an unimpeded charge transfer process to result in boosted pc-HER rate (2027.3 µmol h -1 g -1 ). This work offers a prominent strategy for the reasonable design of efficient photocatalysts at the molecular level for structural regulation and achieves an efficient charge transfer process for the pc-HER process., (© 2023 Wiley-VCH GmbH.)

Background: Benevolent leadership is common in organizations, including hospitals, and is known to have positive effects on employees. Yet, nursing literature lacks sufficient research on its relationships with nurses' behavior., Methods: In March to April 2022, a cross-sectional study was carried out involving 320 nurses employed across various hospitals in Sichuan Province, China. Benevolent leadership, affective commitment, work engagement, and helping behavior were evaluated using the Benevolent Leadership Scale, Affective Commitment Scale, Work Engagement Scale, and Helping Behavior Questionnaire, respectively. The study employed structural equation model and the bootstrap method to investigate the proposed relationships., Results: The SEM analysis results indicated a positive association between benevolent leadership and several outcomes among nurses. Specifically, benevolent leadership was found to be positively associated with nurses' affective commitment (β = 0.58, p < .001), work engagement (β = 0.02, p < .001), and helping behavior (β = 0.17, p = .001). Additionally, there was a significant indirect effect between benevolent leadership and nurses' work engagement through affective commitment (β = 0.08, p = .007) as well as between benevolent leadership and helping behavior through affective commitment (β = 0.16, p < .001)., Conclusions: This study's findings emphasize the crucial role of benevolent leadership in fostering nurses' positive attitudes and behaviors in the workplace. Hospital administrators could promote the benevolent leadership of head nurses to enhance nurses' affective commitment, work engagement, and helping behaviors., (© 2023. The Author(s).)

Objective: The objective of this study is to describe the incidence of injuries and illnesses sustained during the Beijing Winter Olympic Games from 4 February 2022 to 20 February 2022., Methods: We recorded the daily number of athlete injuries and illnesses (1) through the reporting of all National Olympic Committee (NOC) medical teams and (2) in the polyclinic and medical venues by the Beijing 2022 medical staff., Results: In total, 2848 athletes (1276 women, 45%; 1572 men, 55%) from 91 NOCs were followed prospectively for the occurrence of injury and illness. NOC and Beijing 2022 medical staff reported 289 injuries and 109 illnesses, equalling 10.1 injuries and 3.8 illnesses per 100 athletes over the 17-day period. The injury incidence was highest in ski halfpipe (30%), ski big air (28%), snowboard slopestyle (23%) and ski slopestyle (22%), and lowest (1%-2%) in curling, alpine mixed team parallel slalom, Nordic combined and alpine super-G. The illness incidence was highest in ski aerials (10%), skeleton (8%), cross-country skiing (8%) and Nordic combined (7%). In the study period, COVID-19 affected 32 athletes, accounting for 29% of all illnesses affecting 1.1% of all athletes., Conclusion: Overall, 10% of the athletes incurred an injury and 4% an illness during the Beijing Winter Olympic Games. The incidence of illnesses overall, which was the lowest yet recorded in the Winter Olympic Games, and COVID-19 was mitigated through comprehensive countermeasures., Competing Interests: Competing interests: TS works as scientific manager in the Medical & Scientific Department of the International Olympic Committee. Kathrin Steffen is coeditor of the British Journal of Sports Medicine—Injury Prevention and Health Protection. RB is director of the Medical and Scientific Department of the International Olympic Committee. LE is Head of Scientific Activities in the Medical and Scientific Department of the International Olympic Committee, and Editor of the British Journal of Sports Medicine and associate editor of Journal of Bone and Joint Surgery. BGT is an associate editor of the British Journal of Sports Medicine and was a member of the medical staff for the United States at Beijing 2022 Winter Olympic Games., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Traumatic brain injury usually triggers glial scar formation, neuroinflammation, and neurodegeneration. However, the molecular mechanisms underlying these pathological features are largely unknown. Using a mouse model of hippocampal stab injury (HSI), we observed that miR-331, a brain-enriched microRNA, was significantly downregulated in the early stage (0-7 days) of HSI. Intranasal administration of agomir-331, an upgraded product of miR-331 mimics, suppressed reactive gliosis and neuronal apoptosis and improved cognitive function in HSI mice. Finally, we identified IL-1β as a direct downstream target of miR-331, and agomir-331 treatment significantly reduced IL-1β levels in the hippocampus after acute injury. Our findings highlight, for the first time, agomir-331 as a pivotal neuroprotective agent for early rehabilitation of HSI.

Background: In September 2019, the "4 + 7" centralized procurement pilot program was expanded nationwide aiming at reducing drug prices by means of volume-based procurement and using accredited generic drugs for branded drug substitutes. Given the current uncertain effect of the policy outside pilot areas, this study was conducted to evaluate the impact of the National Volume-based Procurement policy on the use of policy-related drugs after expansion., Method: A single-group interrupted time series was applied using drug purchase data, covering 25 months from December 2018 to December 2020. Drugs related to the centralized procurement policy were selected as samples, including 25 first-batch policy-related drugs and 56 alternative drugs. Centralized procured drugs can be divided into bid-winning and non-winning products, where non-winning products were sorted into generic and branded drugs, and alternative products were classified according to different degrees of substitution. Purchase volume, expenditures, and daily costs were measured., Results: After the implementation of the policy, a significant increase was associated with the volume of bid-winning drugs (p < 0.001) and the volume of generic and branded drugs decreased immediately. The DDDc of drugs under the same generic name significantly reduced (an instantaneous drop of bid-winning drugs by approximately 25%, 7.62 CNY for generics and 3.07 CNY for branded drugs), saving 48.2 million CNY of drug expenditures. The policy has a significant effect on the drug for the treatment of cardiovascular diseases and exerted little influence on the drug for the treatment of nervous diseases, and the substitution of generics for antitumor-branded drugs was not obvious. In addition, the procurement volume of alternative drugs appeared to be a "carry-over"., Conclusions: These findings indicated that the policy demonstrated positive effects in terms of price reductions and cost savings and accelerated the substitution of generics against branded drugs. The "patent cliff" for branded drugs has gradually emerged. Besides, a short-term "spillover effect" of the volume of alternative drugs was observed, requiring special attention and vigilance., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Human behavior recognition plays a crucial role in the field of smart education. It offers a nuanced understanding of teaching and learning dynamics by revealing the behaviors of both teachers and students. In this study, to address the exigencies of teaching behavior analysis in smart education, we first constructed a teaching behavior analysis dataset called EuClass. EuClass contains 13 types of teacher/student behavior categories and provides multi-view, multi-scale video data for the research and practical applications of teacher/student behavior recognition. We also provide a teaching behavior analysis network containing an attention-based network and an intra-class differential representation learning module. The attention mechanism uses a two-level attention module encompassing spatial and channel dimensions. The intra-class differential representation learning module utilized a unified loss function to reduce the distance between features. Experiments conducted on the EuClass dataset and a widely used action/gesture recognition dataset, IsoGD, demonstrate the effectiveness of our method in comparison to current state-of-the-art methods, with the recognition accuracy increased by 1-2% on average., 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 © 2023 Zhang, Chen, Tan, Qian, Li, He and Lei.)

Objective: To explore the antihypertensive effect of sacubitril/valsartan and losartan potassium in the treatment of hypertension and the adverse reactions in patients., Methods: A retrospective study was conducted using the medical records of 166 patients with hypertension who were admitted to Hangzhou Fuyang District Lushan sub-district community health service center from June 2022 to June 2023. The control group was treated with losartan potassium, and the observation group was treated with sacubitril/valsartan. Blood pressure, urinary microalbumin, blood urea nitrogen level, liver and kidney function, blood potassium, blood uric acid, cardiac function, inflammatory factors, occurrence of adverse reactions, and treatment efficacy were compared between the two groups., Results: After treatment, the observation group showed significantly lower blood pressure compared to the control group. Furthermore, the observation group exhibited reduced levels of urinary microalbumin and blood urea nitrogen, improved liver and kidney function, decreased inflammatory factor levels, fewer adverse reactions, and a higher treatment efficacy., Conclusion: For patients with hypertension, sacubitril/valsartan has a better treatment efficacy than losartan potassium, because it can effectively reduce blood pressure, the levels of inflammatory factors, and the rate of adverse reactions in patients., Competing Interests: None., (AJTR Copyright © 2023.)

Introduction: The GAP model was widely used as a simple risk "screening" method for patients with idiopathic pulmonary fibrosis (IPF)., Objectives: We sought to validate the GAP model in Chinese patients with IPF to evaluate whether it can accurately predict the risk for mortality., Methods: A total of 212 patients with IPF diagnosed at China-Japan Friendship Hospital from 2015 to 2019 were enrolled. The latest follow-up ended in September 2022. Cumulative mortality of each GAP stage was calculated and compared based on Fine-Gray models for survival, and lung transplantation was treated as a competing risk. The performance of the model was evaluated in terms of both discrimination and calibration., Results: The cumulative mortality in patients with GAP stage III was significantly higher than that in those with GAP stage I or II (Gray's test p < 0.0001). The Harrell c-index for the GAP calculator was 0.736 (95% CI: 0.667-0.864). The discrimination for the GAP staging system were similar with that for the GAP calculator. The GAP model overestimated the mortality rate at 1- and 2-year in patients classified as GAP stage I (6.90% vs. 1.77% for 1-year, 14.20% vs. 6.78% for 2-year)., Conclusions: Our findings indicated that the GAP model overestimated the mortality rate in mild group., (© 2022 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Microglia are the primary source of transglutaminase 2 (TGM2) in the brain; however, the roles of microglial TGM2 in neural development and disease are still not well known. The aim of this study is to elucidate the role and mechanisms of microglial TGM2 in the brain. A mouse line with a specific knockout of Tgm2 in microglia was generated. Immunohistochemistry, Western blot and qRT-PCR assays were performed to evaluate the expression levels of TGM2, PSD-95 and CD68. Confocal imaging, immunofluorescence staining and behavioural analyses were conducted to identify phenotypes of microglial TGM2 deficiency. Finally, RNA sequencing, qRT-PCR and co-culture of neurons and microglia were used to explore the potential mechanisms. Deletion of microglial Tgm2 causes impaired synaptic pruning, reduced anxiety and increased cognitive deficits in mice. At the molecular level, the phagocytic genes, such as Cq1a, C1qb and Tim4, are significantly down-regulated in TGM2-deficient microglia. This study elucidates a novel role of microglial TGM2 in regulating synaptic remodelling and cognitive function, indicating that microglia Tgm2 is essential for proper neural development., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)