Application of real-time shear wave elastography to Achilles tendon hardness evaluation in older adults.

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.

Association between lactate-to-albumin ratio and short-time mortality in patients with acute respiratory distress syndrome.

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.

The relationship between circulating tumor cells in peripheral blood and clinical characteristics of pediatric neuroblastoma and prognostic evaluation.

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.

Osteoporosis screening using QCT-based cutoff value of Hounsfield units in patients with degenerative lumbar diseases.

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/cm3 for osteoporosis and cutoff value of 120 mg/cm3 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 âœ• average CT value of L1-2-0.46 (R2 = 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.

Geometric and Electronic Structure Modulation to Optimize the Charge Transfer of TiO2 for Ultrasensitive and Stable SERS Sensing.

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 TiO2 (Yb-TiO2) highly SERS sensitive superior to pure TiO2, 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-TiO2 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-TiO2 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.

An exploratory clinical study of ß-glucan combined with camrelizumab and SOX chemotherapy as first-line treatment for advanced gastric adenocarcinoma.

Background: ß-glucan has been reported to be a potential natural immune modulator for tumor growth inhibition. We aimed to evaluate the efficacy and safety of ß-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 ß-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 ß-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.

Cocaine amphetamine-regulated transcription peptide inhibits apoptosis in oxygen-glucose deprived neural stem cells.

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.

Association between medication complexity and follow-up care attendance: insights from a retrospective multicenter cohort study across 1,223 Chinese hospitals.

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.

MiR-143-5p regulates the proangiogenic potential of human dental pulp stem cells by targeting HIF-1α/RORA under hypoxia: A laboratory investigation in pulp regeneration.

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 (CoCl2) 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 CoCl2) promoted pulp angiogenesis and dentine formation. In contrast to the levels of proangiogenic factors, miR-143-5p levels decreased with increasing CoCl2 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: CoCl2-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.

Oleanolic acid improves the in vitro developmental competence of early porcine embryos by reducing oxidative stress and ameliorating mitochondrial function.

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.

The "d-p orbital hybridization"-guided design of novel two-dimensional MOFs with high anchoring and catalytic capacities in Lithium - Sulfur batteries.

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 Li2S 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.

Aircraft turnaround time dynamic prediction based on Time Transition Petri Net.

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.

Inhibitors of APE1 redox and ATM synergistically sensitize osteosarcoma cells to ionizing radiation by inducing ferroptosis.

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.

An overview of magnesium-based implants in orthopaedics and a prospect of its application in spine fusion.

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.

LINC00982-encoded protein PRDM16-DT regulates CHEK2 splicing to suppress colorectal cancer metastasis and chemoresistance.

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.

Immunogenicity-masking delivery of uricase against hyperuricemia and gout.

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.

Recent advances in tunable solid-state emission based on α-cyanodiarylethenes: from molecular packing regulation to functional development.

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.

Numerical simulation of the influence of nasal cycle on nasal airflow.

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.

Chlorogenic acid improves the development of porcine parthenogenetic embryos by regulating oxidative stress and ameliorating mitochondrial function.

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.