A randomized, double-blind, placebo-controlled, phase IIa, clinical study on investigating the efficacy and safety of SPH3127 tablet in patients with essential hypertension.

Around 70% of patients diagnosed with hypertension exhibit increased levels of renin. SPH3127, an inventive renin inhibitor, has shown favorable tolerability and sustained pharmacodynamic inhibitory impact on plasma renin activity (PRA) during previous phase I trials. This phase II study was conducted to investigate the efficacy and safety of SPH3127 in patients with essential hypertension. This study was conducted in patients with mild to moderate essential hypertension, utilizing a randomized, double-blind, placebo-controlled design. The patients were administered either tablet of SPH3127 at doses of 50 mg, 100 mg, or 200 mg, or a placebo. A total of 122 patients were included in the study, with 121 patients included in the full analysis set. Among these patients, there were 30 individuals in each subgroup receiving different dosage regimens of SPH3127, and 31 patients in the placebo group. The reductions in mean sitting diastolic blood pressure (msDBP) after 8 weeks compared to baseline were 5.7 ± 9.5, 8.6 ± 8.8, and 3.8 ± 10.6 mmHg in the SPH3127 50-, 100-, and 200 mg groups, respectively. In the placebo group, the reduction was 3.1 ± 8.4 mmHg. The corresponding reductions in mean sitting systolic blood pressure (msSBP) were 11.8 ± 13.0, 13.8 ± 11.2, 11.1 ± 13.1, and 7.7 ± 9.7 mmHg in each respective group. SPH3127 is a promising drug for the treatment of patients with essential hypertension. The recommended dosage is 100 mg daily.Clinical trial registration: This study was registered in ClinicalTrials.gov (NCT03756103).

Construction of the single-diamond-structured titania scaffold-Recreation of the holy grail photonic structure.

As one of the most stunning biological nanostructures, the single-diamond (SD) surface discovered in beetles and weevils exoskeletons possesses the widest complete photonic bandgap known to date and is renowned as the "holy grail" of photonic materials. However, the synthesis of SD is difficult due to its thermodynamical instability compared to the energetically favoured bicontinuous double diamond and other easily formed lattices; thus, the artificial fabrication of SD has long been a formidable challenge. Herein, we report a bottom-up approach to fabricate SD titania networks via a one-pot cooperative assembly scenario employing the diblock copolymer poly(ethylene oxide)-block-polystyrene as a soft template and titanium diisopropoxide bis(acetylacetonate) as an inorganic precursor in a mixed solvent, in which the SD scaffold was obtained by kinetically controlled nucleation and growth in the skeletal channels of the diamond minimal surface formed by the polymer matrix. Electron crystallography investigations revealed the formation of tetrahedrally connected SD frameworks with the space group Fd [Formula: see text] m in a polycrystalline anatase form. A photonic bandgap calculation showed that the resulting SD structure has a wide and complete bandgap. This work solves the complex synthetic enigmas and offers a frontier in hyperbolic surfaces, biorelevant materials, next-generation optical devices, etc.

Revisiting airway epithelial dysfunction and mechanisms in chronic obstructive pulmonary disease: Role of mitochondrial damage.

Chronic exposure to environmental hazards causes airway epithelial dysfunction, primarily impaired physical barriers, immune dysfunction, and repair or regeneration. Impairment of airway epithelial function subsequently leads to exaggerated airway inflammation and remodeling, the main features of chronic obstructive pulmonary disease (COPD). Mitochondrial damage has been identified as one of the mechanisms of airway abnormalities in COPD, which is closely related to airway inflammation and airflow limitation. In this review, we evaluate updated evidence for airway epithelial mitochondrial damage in COPD and focus on the role of mitochondrial damage in airway epithelial dysfunction. In addition, the possible mechanism of airway epithelial dysfunction mediated by mitochondrial damage is discussed in detail, and recent strategies related to airway epithelial-targeted mitochondrial therapy are summarized. Results have shown that dysregulation of mitochondrial quality and oxidative stress may lead to airway epithelial dysfunction in COPD. This may result from mitochondrial damage as a central organelle mediating abnormalities in cellular metabolism. Mitochondrial damage mediates pro-cellular senescence effects due to mitochondrial reactive oxygen species, which effectively exacerbate different types of programmed cell death, participate in lipid metabolism abnormalities, and ultimately promote airway epithelial dysfunction and trigger COPD airway abnormalities. These can be prevented by targeting mitochondrial damage factors and mitochondrial transfer. Thus, because mitochondrial damage is involved in COPD progression as a central factor of homeostatic imbalance in airway epithelial cells, it may be a novel target for therapeutic intervention to restore airway epithelial integrity and function in COPD.

Manganese-based nanomaterials promote synergistic photo-immunotherapy: green synthesis, underlying mechanisms, and multiple applications.

Single phototherapy and immunotherapy have individually made great achievements in tumor treatment. However, monotherapy has difficulty in balancing accuracy and efficiency. Combining phototherapy with immunotherapy can realize the growth inhibition of distal metastatic tumors and enable the remote monitoring of tumor treatment. The development of nanomaterials with photo-responsiveness and anti-tumor immunity activation ability is crucial for achieving photo-immunotherapy. As immune adjuvants, photosensitizers and photothermal agents, manganese-based nanoparticles (Mn-based NPs) have become a research hotspot owing to their multiple ways of anti-tumor immunity regulation, photothermal conversion and multimodal imaging. However, systematic studies on the synergistic photo-immunotherapy applications of Mn-based NPs are still limited; especially, the green synthesis and mechanism of Mn-based NPs applied in immunotherapy are rarely comprehensively discussed. In this review, the synthesis strategies and function of Mn-based NPs in immunotherapy are first introduced. Next, the different mechanisms and leading applications of Mn-based NPs in immunotherapy are reviewed. In addition, the advantages of Mn-based NPs in synergistic photo-immunotherapy are highlighted. Finally, the challenges and research focus of Mn-based NPs in combination therapy are discussed, which might provide guidance for future personalized cancer therapy.

Cell sheet formation enhances the therapeutic effects of adipose-derived stromal vascular fraction on urethral stricture.

Urethral stricture (US) is a common disease in urology, lacking effective treatment options. Although injecting a stem cells suspension into the affected area has shown therapeutic benefits, challenges such as low retention rate and limited efficacy hinder the clinical application of stem cells. This study evaluates the therapeutic impact and the mechanism of adipose-derived vascular fraction (SVF) combined with cell sheet engineering technique on urethral fibrosis in a rat model of US. The results showed that SVF-cell sheets exhibit positive expression of α-SMA, CD31, CD34, Stro-1, and eNOS. In vivo study showed less collagen deposition, low urethral fibrosis, and minimal tissue alteration in the group receiving cell sheet transplantation. Furthermore, the formation of a three-dimensional (3D) tissue-like structure by the cell sheets enhances the paracrine effect of SVF, facilitates the infiltration of M2 macrophages, and suppresses the TGF-ß/Smad2 pathway through HGF secretion, thereby exerting antifibrotic effects. Small animal in vivo imaging demonstrates improved retention of SVF cells at the damaged urethra site with cell sheet application. Our results suggest that SVF combined with cell sheet technology more efficiently inhibits the early stages of urethral fibrosis.

Investigation of clinical significance of ST-segment depression during paroxysmal supraventricular tachycardia.

INTRODUCTION: There are great differences in ST-segment depression during PSVT episodes. The aim of this study is to investigate the clinical significance of ST segment depression during PSVT. METHODS: The study enrolled 333 consecutive patients who were diagnosed with PSVT by electrophysiological test from Jan 1, 2021 to July 31, 2022. The range, magnitude and morphology of ST-segment depression were described. The correlation between ST-segment depression and symptoms of chest tightness, chest pain or hypotension, the correlation between ST-segment depression and coronary stenosis, and the possible influencing factors were analyzed. In addition, the diagnostic efficacy of ST-segment depression for AVRT was determined. RESULTS: ST-segment depression was present in 85% of patients, in 70% of which the depression range was more than six leads. The magnitude of the depression was more significant in precordial leads (P < 0.001). ST-segment depression of >1 mm in limb leads and precordial leads was found in 36.0% and 49.8% of the patients, respectively, while >3 mm was found in 2.4% and 9.6%, respectively. The morphology of ST-segment depression in limb leads was different from that in precordial leads (P < 0.001). Downsloping ST-segment depression was more common in limb leads (limb vs. precordial: 40.5% vs. 12.6%), whereas upsloping depression was more common in precordial leads (limb vs. precordial: 3.0% vs. 23.1%). Correlation analysis showed that ST-segment depression was not correlated with symptoms of chest tightness and pain, nor was it correlated with coronary artery stenosis. The most important influencing factor is the type of PSVT, especially affecting the morphology of depression in limb leads (OR = 10.27 [5.93-17.79], P < 0.001). The sensitivity and specificity of downsloping ST-segment depression in limb leads for diagnosis of AVRT were 75.5% and 76.7%. CONCLUSION: ST-segment depression is a common ECG change during PSVT episodes, and it's not associated with severe coronary stenosis. The type of PSVT has a significant effect on the manifestation of ST-segment depression. The downslope morphology of ST-segment depression in limb leads is helpful in differentiating AVRT from AVNRT.

Designing Low Toxic Deep Eutectic Solvents for the Green Recycle of Lithium-Ion Batteries Cathodes.

The Lithium-ion battery (LIB) is one of the main energy storage equipment. Its cathode material contains Li, Co, and other valuable metals. Therefore, recycling spent LIBs can reduce environmental pollution and resource waste, which is significant for sustainable development. However, traditional metallurgical methods are not environmentally friendly, with high cost and environmental toxicity. Recently, the concept of green chemistry gives rise to environmental and efficient recycling technology, which promotes the transition of recycling solvents from organic solvents to green solvents represented by deep eutectic solvents (DESs). DESs are considered as ideal alternative solvents in extraction processes, attracting great attention due to their low cost, low toxicity, good biodegradability, and high extraction capacity. It is very important to develop the DESs system for LIBs recycling for sustainable development of energy and green economic development of recycling technology. In this work, the applications and research progress of DESs in LIBs recovery are reviewed, and the physicochemical properties such as viscosity, toxicity and regulatory properties are summarized and discussed. In particular, the toxicity data of DESs are collected and analyzed. Finally, the guidance and prospects for future research are put forward, aiming to explore more suitable DESs for recycling valuable metals in batteries.

Delayed care-seeking in international migrant workers with imported malaria in China.

BACKGROUND: Imported malaria cases continue to pose major challenges in China as well as in other countries that have achieved elimination. Early diagnosis and treatment of each imported malaria case is the key to successfully maintaining malaria elimination success. This study aimed to build an easy-to-use predictive nomogram to predict and intervene against delayed care-seeking among international migrant workers with imported malaria. METHODS: A prediction model was built based on cases with imported malaria from 2012 to 2019, in Jiangsu Province, China. Routine surveillance information (e.g. sex, age, symptoms, origin country and length of stay abroad), data on the place of initial care-seeking and the gross domestic product (GDP) of the destination city were extracted. Multivariate logistic regression was performed to identify independent predictors and a nomogram was established to predict the risk of delayed care-seeking. The discrimination and calibration of the nomogram was performed using area under the curve and calibration plots. In addition, four machine learning models were used to make a comparison. RESULTS: Of 2255 patients with imported malaria, 636 (28.2%) sought care within 24 h after symptom onset, and 577 (25.6%) sought care 3 days after symptom onset. Development of symptoms before entry into China, initial care-seeking from superior healthcare facilities and a higher GDP level of the destination city were significantly associated with delayed care-seeking among migrant workers with imported malaria. Based on these independent risk factors, an easy-to-use and intuitive nomogram was established. The calibration curves of the nomogram showed good consistency. CONCLUSIONS: The tool provides public health practitioners with a method for the early detection of delayed care-seeking risk among international migrant workers with imported malaria, which may be of significance in improving post-travel healthcare for labour migrants, reducing the risk of severe malaria, preventing malaria reintroduction and sustaining achievements in malaria elimination.

"Three-in-One" Multifunctional Hollow Nanocages with Colorimetric Photothermal Catalytic Activity for Enhancing Sensitivity in Biosensing.

Immunochromatographic assays (ICAs) have been widely used in the field detection of mycotoxin contaminants. Nevertheless, the lack of multisignal readout capability and the ability of signaling tags to maintain their biological activity while efficiently loading antibodies remain a great challenge in satisfying diverse testing demands. Herein, we proposed a novel three-in-one multifunctional hollow vanadium nanomicrosphere (high brightness-catalytic-photothermal properties)-mediated triple-readout ICA (VHMS-ICA) for sensitive detection of T-2. As the key to this biosensing strategy, vanadium was used as the catalytic-photothermal characterization center, and natural polyphenols were utilized as the bridging ligands for coupling with the antibody while self-assembling with formaldehyde cross-linking into a hollow nanocage-like structure, which offers the possibility of realizing a three-signal readout strategy and improving the coupling efficiency to the antibody while preserving its biological activity. The constructed sensors showed a detection limit (LOD) of 2 pg/mL for T-2, which was about 345-fold higher than that of conventional gold nanoparticle-based ICA (0.596 ng/mL). As anticipated, the detection range of VHMS-ICA was extended about 8-fold compared with the colorimetric signal alone. Ultimately, the proposed immunosensor performed well in maize and oat samples, with satisfactory recoveries. Owing to the synergistic and complementary interactions between distinct signaling modes, the establishment of multimodal immunosensors with multifunctional tags is an efficient strategy to satisfy diversified detection demands.

FSTL3 promotes tumor immune evasion and attenuates response to anti-PD1 therapy by stabilizing c-Myc in colorectal cancer.

Programmed cell death 1 ligand 1 (PDL1)/programmed cell death 1 (PD1) blockade immunotherapy provides a prospective strategy for the treatment of colorectal cancer (CRC), but various constraints on the effectiveness of the treatment are still remaining. As reported in previous studies, follistatin-like 3 (FSTL3) could mediate inflammatory response in macrophages by induction lipid accumulation. Herein, we revealed that FSTL3 were overexpressed in malignant cells in the CRC microenvironment, notably, the expression level of FSTL3 was related to tumor immune evasion and the clinical efficacy of anti-PD1 therapy. Further studies determined that hypoxic tumor microenvironment induced the FSTL3 expression via HIF1α in CRC cells, FSTL3 could bind to the transcription factor c-Myc (354-406 amino acids) to suppress the latter's ubiquitination and increase its stability, thereby to up-regulated the expression of PDL1 and indoleamine 2,3-dioxygenase 1 (IDO1). The results in the immunocompetent tumor models verified that FSLT3 knockout in tumor cells increased the proportion of CD8+ T cells in the tumor microenvironment, reduced the proportion of regulatory T cells (CD25+ Foxp3+) and exhausted T cells (PD1+ CD8+), and synergistically improved the anti-PD1 therapy efficacy. To sum up, FSTL3 enhanced c-Myc-mediated transcriptional regulation to promote immune evasion and attenuates response to anti-PD1 therapy in CRC, suggesting the potential of FSTL3 as a biomarker of immunotherapeutic efficacy as well as a novel immunotherapeutic target in CRC.

Trifunctional Nanocomposites with Colorimetric Magnetic Catalytic Activities Labels in Sandwich Immunochromatographic Detection of Escherichia coli O157:H7.

The emergence of nanoenzymes has catalyzed the robust advancement of the lateral flow immunoassay (LFIA) in recent years. Among them, multifunctional nanocomposite enzymes with core-shell architectures are considered preferable for promoting the sensing ability due to their good biocompatibility, precise control over size, and surface properties etc. Herein, we developed a dual-channel ensured lateral flow immunoassay (DFLIA) platform utilizing a magnetic, colorimetric, and catalytic multifunctional nanocomposite enzyme (Fe3O4@TCPP@Pd) [TCPP, Tetrakis (4-carboxyphenyl) porphyrin] for the ultrasensitive and highly accurate rapid detection of Escherichia coli O157:H7 (E. coli O157:H7). Fe3O4@TCPP@Pd-mAb exhibits superior performance compared to traditional AuNPs, including enhanced sensitivity and an extended linear detection range, benefiting from its high brightness signal, strong magnetic separation ability, and high peroxidase activity (Vmax = 2.32 µM S1-). Moreover, the Fe3O4@TCPP@Pd-labeled mAb probe exhibited exceptional stability and high affinity toward E. coli O157:H7 (with an affinity constant of approximately 1.723 × 109 M-1), indicating its potential for the efficient capture of the pathogen. Impressively, the developed Fe3O4@TCPP@Pd-DFLIA achieved ultrasensitive detection for E. coli O157:H7 with pre- and postcatalytic naked-eye detection sensitivities of 255 cfu/mL and 77 cfu/mL, respectively, representing an approximately 41-fold improvement over the conventional AuNP-based LFIA and also possessed good specificity and reproducibility [relative standard deviation (RSD) < 10%]. Additionally, the established DFLIA exhibited satisfactory recoveries in detecting pork and milk samples, further validating the reliability of this platform for immunoassays and demonstrating its potential for utilization in bioassays and clinical diagnostics.

Toxoplasma gondii Causes Adverse Pregnancy Outcomes by Damaging Uterine Tissue-Resident NK Cells That Secrete Growth-Promoting Factors.

Vertical transmission of the intracellular parasite, Toxoplasma gondii can lead to adverse pregnancy outcomes especially when infection occurs in early pregnancy. Decidual natural killer (dNK) cells accumulate at the maternal-fetal interface in large numbers during early pregnancy. Their nutritional roles during infection with T. gondii remain poorly defined. In the present study, we demonstrated that a functional deficiency of the uterine tissue-resident NK (trNK) cells, a subset of dNK cells, contributes to the adverse pregnancy outcomes induced by T. gondii in early pregnancy. Adverse pregnancy outcomes could be ameliorated by adoptive transfer of trNK cells. Moreover, fetal growth restriction could be improved after supplementation of growth-promoting factors. In addition to the widely recognized disturbance of the immune balance at the interface between the mother and the fetus, our study reveals a novel mechanism in T. gondii that contributes to the adverse pregnancy outcomes.

Development and validation of a novel nomogram model to assess the risk of gastric contents in outpatients undergoing elective sedative gastrointestinal endoscopy procedures.

BACKGROUND: Gastric contents may contribute to patients' aspiration during anesthesia. Ultrasound can accurately assess the risk of gastric contents in patients undergoing sedative gastrointestinal endoscopy (GIE) procedures, but its efficiency is limited. Therefore, developing an accurate and efficient model to predict gastric contents in outpatients undergoing elective sedative GIE procedures is greatly desirable. METHODS: This study retrospectively analyzed 1501 patients undergoing sedative GIE procedures. Gastric contents were observed under direct gastroscopic vision and suctioned through the endoscope. High-risk gastric contents were defined as having solid content or liquid volume > 25 ml and pH < 2.5; otherwise, they were considered low-risk gastric contents. Univariate analysis and multivariate analysis were used to select the independent risk factors to predict high-risk gastric contents. Based on the selected independent risk factors, we assigned values to each independent risk factor and established a novel nomogram. The performance of the nomogram was verified in the testing cohort by the metrics of discrimination, calibration, and clinical usefulness. In addition, an online accessible web calculator was constructed. RESULTS: We found BMI, cerebral infarction, cirrhosis, male, age, diabetes, and gastroesophageal reflux disease were risk factors for gastric contents. The AUROCs were 0.911 and 0.864 in the development and testing cohort, respectively. Moreover, the nomogram showed good calibration ability. Decision curve analysis and Clinical impact curve demonstrated that the predictive nomogram was clinically useful. The website of the nomogram was https://medication.shinyapps.io/dynnomapp/. CONCLUSIONS: This study demonstrates that clinical variables can be combined with algorithmic techniques to predict gastric contents in outpatients. Nomogram was constructed from routine variables, and the web calculator had excellent clinical applicability to assess the risk of gastric contents accurately and efficiently in outpatients, assist anesthesiologists in assessment and identify the most appropriate patients for ultrasound.

Assessing the risk of malaria local transmission and re-introduction in China from pre-elimination to elimination: A systematic review.

Assessing the risk of malaria local transmission and re-introduction is crucial for the preparation and implementation of an effective elimination campaign and the prevention of malaria re-introduction in China. Therefore, this review aims to evaluate the risk factors for malaria local transmission and re-introduction in China over the period of pre-elimination to elimination. Data were obtained from six databases searched for studies that assessed malaria local transmission risk before malaria elimination and re-introduction risk after the achievement of malaria elimination in China since the launch of the NMEP in 2010, employing the keywords "malaria" AND ("transmission" OR "re-introduction") and their synonyms. A total of 8,124 articles were screened and 53 articles describing 55 malaria risk assessment models in China from 2010 to 2023, including 40 models assessing malaria local transmission risk (72.7%) and 15 models assessing malaria re-introduction risk (27.3%). Factors incorporated in the 55 models were extracted and classified into six categories, including environmental and meteorological factors (39/55, 70.9%), historical epidemiology (35/55, 63.6%), vectorial factors (32/55, 58.2%), socio-demographic information (15/26, 53.8%), factors related to surveillance and response capacity (18/55, 32.7%), and population migration aspects (13/55, 23.6%). Environmental and meteorological factors as well as vectorial factors were most commonly incorporated in models assessing malaria local transmission risk (29/40, 72.5% and 21/40, 52.5%) and re-introduction risk (10/15, 66.7% and 11/15, 73.3%). Factors related to surveillance and response capacity and population migration were also important in malaria re-introduction risk models (9/15, 60%, and 6/15, 40.0%). A total of 18 models (18/55, 32.7%) reported the modeling performance. Only six models were validated internally and five models were validated externally. Of 53 incorporated studies, 45 studies had a quality assessment score of seven and above. Environmental and meteorological factors as well as vectorial factors play a significant role in malaria local transmission and re-introduction risk assessment. The factors related to surveillance and response capacity and population migration are more important in assessing malaria re-introduction risk. The internal and external validation of the existing models needs to be strengthened in future studies.

O-H bond activation of ß,γ-unsaturated oximes via hydrogen atom transfer (HAT) and photoredox dual catalysis.

Hydrogen atom transfer (HAT) and photoredox dual catalysis provides a unique opportunity in organic synthesis, enabling the direct activation of C/Si/S-H bonds. However, the activation of O-H bonds of ß,γ-unsaturated oximes poses a challenge due to their relatively high redox potential, which exceeds the oxidizing capacity of most currently developed photocatalysts. We here demonstrate that the combination of HAT and photoredox catalysis allows the activation of O-H bond of ß,γ-unsaturated oximes. The strategy effectively addresses the oxime's high redox potential and offers a universal pathway for iminoxyl radical formation. Leveraging the versatility of this approach, a diverse array of valuable heterocycles have been synthesized with the use of different radical acceptors. Mechanistic studies confirm a HAT process for the O-H bond activation.

An AMPK agonist suppresses the progress of colorectal cancer by regulating the polarization of TAM to M1 through inhibition of HIF-1α and mTOR signal pathway.

OBJECTIVE: This study aimed to evaluate the impact of an adenosine monophosphate-activated protein kinase (AMPK) agonist, metformin (MET), on the antitumor effects of macrophages and to determine the underlying mechanism involved in the process. MATERIALS AND METHODS: M0 macrophages were derived from phorbol-12-myristate-13-acetate-stimulated THP-1 cells. RESULTS: The levels of tumor necrosis factor-alpha (TNF-α) and human leukocyte antigen-DR (HLA-DR) were decreased in macrophages incubated with HCT116 cells, whereas those of arginase-1 (Arg-1), CD163, and CD206 were elevated; these effects were reversed by MET. The transfection of small interfering (si) RNA abrogated the influence of MET on the expression of the M1/M2 macrophage biomarkers. MET significantly suppressed the proliferation and migration abilities of HCT116 cells incubated with M0 macrophages; these actions were reversed by siRNA transfection against AMPK. The hypoxia-inducible factor 1-alpha (HIF-1α), phosphorylated protein kinase B (p-AKT), and phosphorylated mammalian target of rapamycin (p-mTOR) levels were reduced by the introduction of MET and promoted by siRNA transfection against AMPK. In addition, the levels of HIF-1α, p-AKT, and p-mTOR suppressed by MET were markedly increased following the transfection of siRNA against AMPK. CONCLUSION: These findings indicate that MET can repress the progression of colorectal cancer by transforming tumor-associated macrophages to the M1phenotype via inhibition of the HIF-1α and mTOR signaling pathways.

Small-molecule exhibits anti-tumor activity by targeting the RNA m6A reader IGF2BP3 in ovarian cancer.

Based on its absence in normal tissues and its role in tumorigenesis and tumor progression, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader of N6-methyladenosine (M6A) on RNA, represents a putative valuable and specific target for some cancer therapy. In this study, we performed bioinformatic analysis and immunohistochemistry (IHC) to find that IGF2BP3 was highly expressed in tumor epithelial cells and fibroblasts of ovarian cancer (OC), and was associated with poor prognosis, metastasis, and chemosensitivity in OC patients. In particular, we discovered that knockdown IGF2BP3 expression inhibited the malignant phenotype of OC cell lines by decreasing the protein levels of c-MYC, VEGF, CDK2, CDK6, and STAT1. To explore the feasibility of IGF2BP3 as a therapeutic target for OC, a small molecular AE-848 was designed and screened by molecular operating environment (MOE), which not only could duplicate the above results of knockdown assay but also reduced the expression of c-MYC in M2 macrophages and tumor-associated macrophages and promoted the cytokine IFN-γ and TNF-α secretion. The pharmacodynamic models of two kinds of OC bearing animals were suggested that systemic therapy with AE-848 significantly inhibited tumor growth by reducing the expression of tumor-associated antigen (c-MYC/VEGF/Ki67/CDK2) and improving the anti-tumor effect of macrophages. These results suggest that AE-848 can inhibit the growth and progression of OC cells by disrupting the stability of the targeted mRNAs of IGF2BP3 and may be a targeted drug for OC treatment.

Role of Nrf2 and exercise in alleviating COPD-induced skeletal muscle dysfunction.

Chronic obstructive pulmonary disease (COPD) is a complex chronic respiratory disease with cumulative impacts on multiple systems, exhibiting significant extrapulmonary impacts, and posing a serious public health problem. Skeletal muscle dysfunction is one of the most pronounced extrapulmonary effects in patients with COPD, which severely affects patient prognosis and mortality primarily through reduced productivity resulting from muscle structural and functional alterations. Although the detailed pathogenesis of COPD has not been fully determined, some researchers agree that oxidative stress plays a significant role. Oxidative stress not only catalyzes the progression of pulmonary symptoms but also drives the development of skeletal muscle dysfunction. Nuclear factor erythroid 2-related factor 2 (Nrf2), is a key transcription factor that regulates the antioxidant response and plays an enormous role in combating oxidative stress. In this review, we have summarized current research on oxidative stress damage to COPD skeletal muscle and analyzed the role of Nrf2 in improving skeletal muscle dysfunction in COPD through exercise. The results suggest that oxidative stress drives the occurrence and development of skeletal muscle dysfunction in COPD. Exercise may improve skeletal muscle dysfunction in patients with COPD by promoting the dissociation of Kelch-like ECH-associated protein 1 (Keap1) and Nrf2, inducing sequestosome1(p62) phosphorylation to bind with Keap1 competitively leading to Nrf2 stabilization and improving dynamin-related protein 1-dependent mitochondrial fission. Nrf2 may be a key target for exercise anti-oxidative stress to alleviate skeletal muscle dysfunction in COPD.

Inhibition of SIRT6 aggravates p53-mediated ferroptosis in acute lung injury in mice.

Although studies have shown that protein 53 (p53)-mediated ferroptosis is involved in acute lung injury (ALI), the mechanism of its regulation remains unclear. The protective effects of Sirtuin 6 (SIRT6), a histone deacetylase, have been demonstrated in multiple diseases; however, further studies are needed to elucidate the role of SIRT6 in ALI. In the present study, we hypothesize that SIRT6 protects against lipopolysaccharide (LPS)-induced ALI by regulating p53-mediated ferroptosis. We observed that the inhibition of ferroptosis prevented LPS-induced ALI. The knockout of p53 blocked LPS-induced ferroptosis and ALI, suggesting that p53 facilitated ALI by promoting ferroptosis. In addition, the inhibition of SIRT6 aggravated LPS-induced ferroptosis and ALI, while the depression of ferroptosis blocked the exacerbation of lung injury induced by SIRT6 inhibition. The results suggest that SIRT6 protects against ALI by regulating ferroptosis. Furthermore, the inhibition of SIRT6 reinforced the p53 acetylation and the deletion of p53 rescued the exacerbation of ferroptosis induced by SIRT6 inhibition. The findings indicate that SIRT6 regulates the acetylation of p53 and prevents p53-mediated ferroptosis. In conclusion, our results indicate that SIRT6 protects against LPS-induced ALI by regulating p53-mediated ferroptosis, thereby demonstrating that SIRT6 holds great promise as a therapeutic target for ALI.

Novel Dumbbell-like CeVO4 Carrier-Based Immunochromatographic Assay for Highly Sensitive T-2 Toxin Detection in Food Samples.

Improving the sensitivity of immunochromatographic assays (ICAs) lies in the signal strength and probe activity of the labeled tracers, and the color properties and structure of the labeled tracers are key factors affecting the biological activity. In this study, cerium vanadate (CeVO4) of different sizes and shapes (230, 1058, and 710 nm) was synthesized to investigate its impact on the performance of ICA for T-2 detection. The prepared CeVO4 possessed outstanding stability, a large specific surface area, superior biocompatibility, and high compatibility with T-2 mAb (affinity constant was 3.14 × 108 M-1). As labeling probes for competitive ICA, the results showed that 1058 nm of CeVO4 as labels exhibited the best detection performance, with a limit of detection (LOD) of 0.079 ng/mL, which was substantially 19-fold less than the average of gold nanoparticle ICA. Additionally, CeVO4-ICA was effectively used to detect T-2 toxin, and the recovery rate for spiking corn and oatmeal samples was determined to be 81.27-115.44% (relative standard deviation <9.16%). The above information demonstrates the efficiency and applicability of CeVO4-ICA as a technique for quick and thorough identification of T-2 toxin residues in food.