Liver autotransplantation and atrial reconstruction on a patient with multiorgan alveolar echinococcosis: a case report.

BACKGROUND: Alveolar echinococcosis (AE) primarily affects the liver and potentially spreads to other organs. Managing recurrent AE poses significant challenges, especially when it involves critical structures and multiple major organs. CASE PRESENTATION: We present a case of a 59-year-old female with recurrent AE affecting the liver, heart, and lungs following two previous hepatectomies, the hepatic lesions persisted, adhering to major veins, and imaging revealed additional diaphragmatic, cardiac, and pulmonary involvement. The ex vivo liver resection and autotransplantation (ELRA), first in human combined with right atrium (RA) reconstruction were performed utilizing cardiopulmonary bypass, and repairs of the pericardium and diaphragm. This approach aimed to offer a potentially curative solution for lesions previously considered inoperable without requiring a donor organ or immunosuppressants. The patient encountered multiple serious complications, including atrial fibrillation, deteriorated liver function, severe pulmonary infection, respiratory failure, and acute kidney injury (AKI). These complications necessitated intensive intraoperative and postoperative care, emphasizing the need for a comprehensive management strategy in such complicated high-risk surgeries. CONCLUSIONS: The multidisciplinary collaboration in this case proved effective and yielded significant therapeutic outcomes for a rare case of advanced hepatic, cardiac, and pulmonary AE. The combined approach of ELRA and RA reconstruction under extracorporeal circulation demonstrated distinct advantages of ELRA in treating complex HAE. Meanwhile, assessing diaphragm function during the perioperative period, especially in patients at high risk of developing pulmonary complications and undergoing diaphragmectomy is vital to promote optimal postoperative recovery. For multi-resistant infection, it is imperative to take all possible measures to mitigate the risk of AKI if vancomycin administration is deemed necessary.

Fluoride exposure during puberty induces testicular impairment via ER stress-triggered apoptosis in mice.

Fluoride, a ubiquitous environmental compound, carries significant health risks at excessive levels. This study investigated the reproductive toxicity of fluoride exposure during puberty in mice, focusing on its impact on testicular development, spermatogenesis, and underlying mechanisms. The results showed that fluoride exposure during puberty impaired testicular structure, induced germ cell apoptosis, and reduced sperm counts in mice. Additionally, the SOD activity and GSH content were significantly decreased, while MDA content was significantly elevated in the NaF group. Immunohistochemistry showed an increase in the number of cells positive for GRP78, a key ER stress marker. Moreover, qRT-PCR and Western blot analyses confirmed the upregulation of both Grp78 mRNA and protein expression, as well as increased mRNA expression of other ER stress-associated genes (Grp94, chop, Atf6, Atf4, and Xbp1) and enhanced protein expression of phosphorylated PERK, IRE1α, eIF2α, JNK, XBP-1, ATF-6α, ATF-4, and CHOP. In conclusion, our findings demonstrate that fluoride exposure during puberty impairs testicular structure, induces germ cell apoptosis, and reduces sperm counts in mice. ER stress may participate in testicular cell apoptosis, and contribute to the testicular damage and decreased sperm counts induced by fluoride.

CXC chemokine receptor type 5 may induce trophoblast dysfunction and participate in the processes of unexplained missed abortion, wherein p-ERK and interleukin-6 may be involved.

Chemokines regulate the trophoblast dysfunction involved in the occurrence and development of pathological pregnancy, including missed abortions. In particular, CXC chemokine receptor type 5 mediates cell proliferation, migration, and inflammation; nonetheless, its role in missed abortions remains unclear. This study aimed to examine the expression of CXC chemokine receptor type 5 in missed abortions and to investigate the effects of CXC chemokine receptor type 5 on the biological behaviour of trophoblasts, as well as the underlying mechanisms. Our results indicated that CXC chemokine receptor type 5 was upregulated in the villi of women who experienced unexplained missed abortions, as compared with those who had normal pregnancies. CXC chemokine receptor type 5 inhibited the proliferation and migration of human first-trimester trophoblast/simian virus cells but promoted cell apoptosis. With respect to its mechanisms, CXC chemokine receptor type 5 activated the extracellular signal-regulated protein kinase 1/2 signalling pathway and upregulated the secretion of interleukin-6; however, it had no effect on the secretion of tumour necrosis factor-α. In conclusion, our findings suggest that CXC chemokine receptor type 5 induces trophoblast dysfunction and participates in the processes of unexplained missed abortions, wherein p-ERK and interleukin-6 may be involved.

Identification of the body fluid donor in mixtures through target mRNA cSNP sequencing.

In forensic practice, mixture stains containing various body fluids are common, presenting challenges for interpretation, particularly in multi-contributor mixtures. Traditional STR profiles face difficulties in such scenarios. Over recent years, RNA has emerged as a promising biomarker for body fluid identification, and mRNA polymorphism has shown excellent performance in identifying body fluid donors in previous studies. In this study, a massively parallel sequencing assay was developed, encompassing 202 coding region SNPs (cSNPs) from 45 body fluid/tissue-specific genes to identify both body fluid/tissue origin and the respective donors, including blood, saliva, semen, vaginal secretion, menstrual blood, and skin. The specificity was evaluated by examining the single-source body fluids/tissue and revealed that the same body fluid exhibited similar expression profiles and the tissue origin could be identified. For laboratory-generated mixtures containing 2-6 different components and mock case mixtures, the donor of each component could be successfully identified, except for the skin donor. The discriminatory power for all body fluids ranged from 0.997176329 (menstrual blood) to 0.99999999827 (blood). The concordance of DNA typing and mRNA typing for the cSNPs in this system was also validated. This cSNP typing system exhibits excellent performance in mixture deconvolution.

A method of identifying the high-risk mutations of sudden cardiac death at KCNQ1 and KCNH2 genes.

Sudden Cardiac Death (SCD) often shows negative anatomy results after a systemic autopsy and the gene mutations of potassium channel play a key role in the etiology of SCD. We established a feasible system to detect SCD-related mutations and investigated the mutations at KCNQ1 and KCNH2 genes in the Chinese population. We established a mutation detection system combined with multiplex PCR, SNaPshot technique, and capillary electrophoresis. We genotyped 101 putative mutations at KCNQ1 and KCNH2 genes in 60 SCD of negative anatomy and 50 controls using the established assay and compared Odd Ratio (OR). Four coding variants were identified in the KCNQ1 gene: S546S, I145I, P448R, and G643S. The mutations of I145I and S546S did not differ significantly in the SCD compared with controls. 21 SCD individuals (35 %) and 1 control individual (2 %) showed a genotype of C/G at P448R (OR = 17.5, 95 % CI [2.40-127.82]). 24 SCD individuals (40 %) and 1 control individual (2 %) showed a genotype of C/G at G643S (OR = 20.0, 95 % CI [2.75-145.25]). We established a robust assay for rapid screening the putative SCD-related mutations in KCNQ1 and KCNH2 genes. The new assay in our study is easily amenable to the majority of laboratories without the need for new specialized equipment. Our method will meet the increasing requirement of mutation screening for SCD in regular DNA laboratories and will help screen mutations in those dead of SCD and their relatives.

Bio-inspired gradient poly(lactic acid) nanofibers for active capturing of PM0.3 and real-time respiratory monitoring.

The concept of bio-inspired gradient hierarchies, in which the well-defined MOF nanocrystals serve as active nanodielectrics to create electroactive shell at poly(lactic acid) (PLA) nanofibers, is introduced to promote the surface activity and electroactivity of PLA nanofibrous membranes (NFMs). The strategy enabled significant refinement of PLA nanofibers during coaxial electrospinning (∼40 % decline of fiber diameter), accompanied by remarkable increase of specific surface area (nearly 1.5 m2/g), porosity (approximately 85 %) and dielectric constants for the bio-inspired gradient PLA (BG-PLA) NFMs. It largely boosted initial electret properties and electrostatic adsorption capability of BG-PLA NFMs, as well as charge regeneration by TENG mechanisms even under high-humidity environment. The BG-PLA NFMs thus featured exceptionally high PM0.3 filtration efficiencies with well-controlled air resistance (94.3 %, 163.4 Pa, 85 L/min), in contrast to the relatively low efficiency of only 80.0 % for normal PLA. During the application evaluation of outdoor air purification, excellent long-term filtering performance was demonstrated for the BG-PLA for up to 4 h (nearly 98.0 %, 53 Pa), whereas normal PLA exhibited a gradually declined filtration efficiency and an increased pressure drop. Moreover, the BG-PLA NFMs of increased electroactivity were ready to generate tribo-output currents as driven by respiratory vibrations, which enabled real-time monitoring of electrophysiological signals. This bio-inspired gradient strategy opens up promising pathways to engender biodegradable nanofibers of high surface activity and electroactivity, which has significant implications for intelligent protective membranes.

A massive pulmonary arteriovenous fistula complicated with coronary atherosclerotic heart disease treated by interventional therapy: a case report.

BACKGROUND: Pulmonary arteriovenous fistula (PAVF) is a rare disease, and its symptoms lack specificity. For patients with coronary heart disease(CHD), hypertension and other common cardiovascular diseases, PAVF is easy to be ignored. We presented a case of massive PAVF complicated with coronary atherosclerotic heart disease by interventional treatment to improve the understanding of this complex disease. CASE PRESENTATION: A 77-year-old female patient was admitted to the hospital due to chest tightness and shortness of breath following activities, which was diagnosed with CHD and hypoxemia in other hospitals. Coronary angiography showed that the patient had severe stenosis of coronary artery while pulmonary vascular DSA showing the patient had PAVF. After interventional therapy of both coronary artery and PAVF, the patient's symptoms were significantly improved. CONCLUSION: We presented a case of massive PAVF complicated with CHD by interventional treatment. For patients with unexplained hypoxemia and symptoms similar with CHD, the possibility of PAVF often leads to oversight, and various auxiliary examinations should be improved to avoid missed diagnosis. And intervention treatment should be carried out to improve the prognosis of patients as much as possible.

Enhancing the Photosensitivity of Hypocrellin A by Perylene Diimide Metallacage-Based Host-Guest Complexation for Photodynamic Therapy.

The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy. Here, we report two perylene diimide-based metallacages that can form stable host-guest complexes with planar conjugated molecules including polycyclic aromatic hydrocarbons and photosensitizers (hypocrellin A). Such host-guest complexation not only prevents the aggregation of photosensitizers in aqueous environments, but also offers fluorescence resonance energy transfer (FRET) from the metallacage to the photosensitizers to further improve the singlet oxygen generation (ΦΔ = 0.66). The complexes are further assembled with amphiphilic polymers, forming nanoparticles with improved stability for anticancer study. Both in vitro and in vivo studies indicate that the nanoparticles display excellent anticancer activities upon light irradiation, showing great potential for cancer photodynamic therapy. This study provides a straightforward and effective approach for enhancing the photosensitivity of conventional photosensitizers via host-guest complexation-based FRET, which will open a new avenue for host-guest chemistry-based supramolecular theranostics.

Therapeutic Inhibition of LincRNA-p21 Protects Against Cardiac Hypertrophy.

BACKGROUND: Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. Recent studies have implicated long noncoding RNAs in cardiac hypertrophy and cardiomyopathy, but their significance and mechanism(s) of action are not well understood. METHODS: We measured lincRNA-p21 RNA and H3K27ac levels in the hearts of dilated cardiomyopathy patients. We assessed the functional role of lincRNA-p21 in basal and surgical pressure-overload conditions using loss-of-function mice. Genome-wide transcriptome analysis revealed dysregulated genes and pathways. We labeled proteins in proximity to full-length lincRNA-p21 using a novel BioID2-based system. We immunoprecipitated lincRNA-p21-interacting proteins and performed cell fractionation, ChIP-seq (chromatin immunoprecipitation followed by sequencing), and co-immunoprecipitation to investigate molecular interactions and underlying mechanisms. We used GapmeR antisense oligonucleotides to evaluate the therapeutic potential of lincRNA-p21 inhibition in cardiac hypertrophy and associated heart failure. RESULTS: lincRNA-p21 was induced in mice and humans with cardiomyopathy. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 pathway. Mechanistically, lincRNA-p21 is bound to the scaffold protein KAP1. lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulates pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. GapmeR antisense oligonucleotide depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21. CONCLUSIONS: These findings advance our understanding of the functional significance of stress-induced long noncoding RNA in cardiac hypertrophy and demonstrate the potential of lincRNA-p21 as a novel therapeutic target for cardiac hypertrophy and subsequent heart failure.

Multifunctional Metal-Organic Frameworks Driven Three-Dimensional Folded Paper-Based Microfluidic Analysis Device for Chlorpyrifos Detection.

Chlorpyrifos (CPF) residues in food pose a serious threat to ecosystems and human health. Herein, we propose a three-dimensional folded paper-based microfluidic analysis device (3D-µPAD) based on multifunctional metal-organic frameworks, which can achieve rapid quantitative detection of CPF by fluorescence-colorimetric dual-mode readout. Upconversion nanomaterials were first coupled with a bimetal organic framework possessing peroxidase activity to create a fluorescence-quenched nanoprobe. After that, the 3D-µPAD was finished by loading the nanoprobe onto the paper-based detection zone and spraying it with a color-developing solution. With CPF present, the fluorescence intensity of the detection zone gradually recovers, the color changes from colorless to blue. This showed a good linear relationship with the concentration of CPF, and the limits of detection were 0.028 (fluorescence) and 0.043 (colorimetric) ng/mL, respectively. Moreover, the 3D-µPAD was well applied in detecting real samples with no significant difference compared with the high-performance liquid chromatography method. We believe it has huge potential for application in the on-site detection of food hazardous substance residues.

Robot-aided assessment and associated brain lesions of impaired ankle proprioception in chronic stroke.

BACKGROUND: Impaired ankle proprioception strongly predicts balance dysfunction in chronic stroke. However, only sparse data on ankle position sense and no systematic data on ankle motion sense dysfunction in stroke are available. Moreover, the lesion sites underlying impaired ankle proprioception have not been comprehensively delineated. Using robotic technology, this study quantified ankle proprioceptive deficits post-stroke and determined the associated brain lesions. METHODS: Twelve adults with chronic stroke and 13 neurotypical adults participated. A robot passively plantarflexed a participant's ankle to two distinct positions or at two distinct velocities. Participants subsequently indicated which of the two movements was further/faster. Based on the stimulus-response data, psychometric just-noticeable-difference (JND) thresholds and intervals of uncertainty (IU) were derived as measures on proprioceptive bias and precision. To determine group differences, Welch's t-test and the Wilcoxon-Mann-Whitney test were performed for the JND threshold and IU, respectively. Voxel-based lesion subtraction analysis identified the brain lesions associated with observed proprioceptive deficits in adults with stroke. RESULTS: 83% of adults with stroke exhibited abnormalities in either position or motion sense, or both. JND and IU measures were significantly elevated compared to the control group (Position sense: + 77% in JND, + 148% in IU; Motion sense: +153% in JND, + 78% in IU). Adults with stroke with both impaired ankle position and motion sense had lesions in the parietal, frontal, and temporoparietal regions. CONCLUSIONS: This is the first study to document the magnitude and frequency of ankle position and motion sense impairment in adults with chronic stroke. Proprioceptive dysfunction was characterized by elevated JND thresholds and increased uncertainty in perceiving ankle position/motion. Furthermore, the associated cortical lesions for impairment in both proprioceptive senses were largely overlapping.

Enabling endogenous distributed acoustic sensing in a digital subcarrier coherent transmission system.

To monitor the health of the fiber network and its ambient environment in densely populated access/metro network areas, in this Letter, an endogenous distributed acoustic sensing (DAS) has been proposed and achieved in a coherent digital subcarrier multiplexing (DSCM) system. Rather than specially allocating a sensing probe in general integrated communication and sensing schemes, the fractional Fourier transformed (FrFT) training sequence (TS) designated for time/frequency synchronization in DSCM coherent communications has been repurposed for sensing. While achieving excellent synchronization performance of communication, the FrFT-based TS can also be concurrently utilized to perform distributed vibration sensing. Experimental results demonstrate that the FrFT-based timing/frequency synchronization sequence is repurposed to achieve a DAS sensitivity of 70 p ε/Hz at a spatial resolution of 5 m, along with 100-Gb/s 16 quadrature amplitude modulation (QAM) DSCM transmission, without a loss of spectral efficiency.

Fraxinellone alleviates colitis-related intestinal fibrosis by blocking the circuit between PD-1+ Th17 cells and fibroblasts.

BACKGROUND: Excessive activation of colonic fibroblasts and differentiation of T helper 17 (Th17) cells are the key steps for intestinal fibrogenesis in the process of inflammatory bowel disease (IBD). Although both transforming growth factor-beta (TGF-ß)/Mothers Against Decapentaplegic Homolog (SMAD) 3-induced fibroblasts activation and interleukin (IL)-6/signal transducer and activator of transcription (STAT) 3-induced Th17 differentiation have been well studied, the crosstalk between fibroblasts and Th17 cells in the process of intestinal fibrogenesis needs to be unveiled. METHODS: In this study, the activation of colonic fibroblasts was induced with dextran sulfate sodium salt (DSS) and TGF-ß in vivo and in vitro respectively. P-SMAD3 and its downstream targets were quantified using RT-PCR, western blot and immunofluorescence. The differentiation of programmed death 1 (PD-1) + Th17 and activation of fibroblasts were quantified by FACS. PD-1+ Th17 cells and fibroblasts were co-cultured and cytokines in the supernatant were tested by ELISA. The anti-fibrosis effects of different chemical compounds were validated in vitro and further confirmed in vivo. RESULTS: The colonic fibroblasts were successfully activated by DSS and TGF-ß in vivo and in vitro respectively, as activation markers of fibroblasts (p-SMAD3 and its downstream targets such as Acta2, Col1a1 and Ctgf) were significantly increased. The activated fibroblasts produced more IL-6 compared with their inactivated counterparts in vivo and in vitro. The proinflammatory cytokine IL-6 induced PD-1+ Th17 differentiation and TGF-ß that in return promoted the activation of colonic fibroblasts. Fraxinellone inhibited TGF-ß+ PD-1+ Th17 cells via deactivating STAT3. CONCLUSIONS: The reciprocal stimulation constructed a circuit of PD-1+ Th17 cells and fibroblasts that accelerated the fibrosis process. Fraxinellone was selected as the potential inhibitor of the circuit of PD-1+ Th17 cells and fibroblasts in vivo and in vitro. Inhibiting the circuit of PD-1+ Th17 cells and fibroblasts could be a promising strategy to alleviate intestinal fibrosis.

Knowledge, attitude, practice and illness perception toward subarachnoid hemorrhage prevention and management among intracranial aneurysm patients.

OBJECTIVE: This study aims to explore the knowledge, attitude, practice and illness perception toward prevention and management of subarachnoid hemorrhages (SAH) among intracranial aneurysm (IA) patients. METHODS: A cross-sectional study was conducted between March 2023 and June 2023; demographic characteristics and KAP scores were collected by a self-administered questionnaire and analyzed by linear regression and path analysis. RESULTS: A total of 455 patients with IA were included, of them 26.37% experienced SAH before. Mean knowledge, attitude and practice scores were 16.60 ± 5.86, 16.39 ± 1.84, and 35.07 ± 3.51, respectively. The linear regression showed ethnic minority, married, education, family members in healthcare system, monthly per capita household income, experience ruptured intracranial aneurysms, smoking, hypertension, hyperlipidemia, diabetes, and aortic lesion were associated with knowledge scores. Age, ethnic minority, urban residence, education, family members in healthcare system, monthly per capita household income, duration of IA ≥6 months, experience ruptured intracranial aneurysms, smoking, diabetes, and aortic lesion were associated with attitude scores. Age, urban residence, monthly per capita household income, duration of IA ≥6 months, experience of ruptured intracranial aneurysms, smoking, diabetes, and aortic lesion were associated with practice scores. According to the path analysis, knowledge directly affected illness perception (ß=0.156, P<0.001) and attitude (ß=0.708, P<0.001), while attitude (ß=0.909, P<0.001) and illness perception (ß=0.039, P=0.027) affected practice. CONCLUSIONS: Patients had positive attitudes towards SAH prevention and management, but a substantial knowledge gap was found along with notably delayed medical help-seeking behavior.

miR-30a-5p attenuates hypoxia/reoxygenation-induced cardiomyocyte apoptosis by regulating PTEN protein expression and activating PI3K/Akt signaling pathway.

BACKGROUND: This study was designed to investigate the mechanism by which miR-30a-5p mediates cardiomyocyte apoptosis after acute myocardial infarction (AMI) induced by hypoxia/reoxygenation (H/R). METHODS: Differentially expressed miRNAs were analyzed by RNA high-throughput sequencing in acute myocardial infarction (ST-elevation myocardial infarction) patients versus healthy individuals (controls). The H/R model was used to assess the regulatory mechanism of miRNAs in AMI. Lentivirus-associated vectors were used to overexpress or knock down miR-30a-5p in cellular models. The pathological mechanisms of miR-30a-5p regulating the development of acute myocardial infarction were serially explored by qPCR, bioinformatics, target gene prediction, dual luciferase, enzyme-linked immunosorbent assays (ELISAs) and Western blotting. RESULTS: The results showed that the expression of miR-30a-5p was significantly increased in AMI patients and H9C2 cells. Hypoxia decreased cardiomyocyte survival over time, and reoxygenation further reduced cell survival. Bax and Phosphatase and tensin homolog (PTEN)were suppressed, while Bcl-2 was upregulated. Additionally, miR-30a-5p specifically targeted the PTEN gene. According to the GO and KEGG analyses, miR-30a-5p may participate in apoptosis by interacting with PTEN. The miR-30a-5p mimic decreased the expression of apoptosis-related proteins and the levels of the proinflammatory markers IL-1ß, IL-6, and TNF-α by activating the PTEN/PI3K/Akt signaling pathway. Conversely, anti-miR-30a-5p treatment attenuated these effects. Additionally, silencing PTEN and anti-miR-30a-5p had opposite effects on H/R-induced cell apoptosis. CONCLUSIONS: miR-30a-5p plays a crucial role in cardiomyocyte apoptosis after hypoxia-induced acute myocardial infarction. Our findings provide translational evidence that miR-30a-5p is a novel potential therapeutic target for AMI.

Synergistic Catalytic Performance of Pt-Au Bimetallic Catalysts on High-Crystallinity ZSM-23 Zeolite for Hexadecane Hydroisomerization: Metal-Acid Balance and Enhanced Isomerization Selectivity.

Highly crystalline ZSM-23 zeolite, exhibiting a distinctive dumbbell morphology, was synthesized via a hydrothermal method. Bifunctional catalysts, comprising single metals (Pt or Au) and bimetals (Pt-Au), were successfully prepared by using a positional precipitation method. The hydroisomerization of hexadecane served as a model reaction to assess the catalytic performance arising from the synergistic effects of bimetallic active sites. In comparison to single-metal catalysts, 0.3Au0.7Pt/ZSM-23 demonstrated increased n-C16 conversion, while 0.5Au0.5Pt/ZSM-23 exhibited enhanced i-C16 selectivity, achieving the highest i-C16 yield. The bimetallic catalyst not only finely tuned the metal site activity through bimetallic synergy but also achieved a superior balance between metal and acid catalysis, resulting in improved catalytic performance in the n-C16 hydroisomerization. The Pt-Au bimetallic catalyst approached the ideal requirements for a hydroisomerization catalyst, achieving a harmonious balance of metal and acid catalysis.

Abnormal methylation mediated upregulation of LINC00857 boosts malignant progression of lung adenocarcinoma by modulating the miR-486-5p/NEK2 axis.

LINC00857 is frequently dysregulated in varying cancers, which in turn exerts carcinogenic effects; however, its DNA methylation status in promoter region and molecular mechanisms underlying the progression of lung adenocarcinoma (LUAD) remain rarely understood. Through bioinformatics analysis, we examined the expression state and methylation site of LINC00857 in LUAD and further investigated the properties of LINC00857 as a competitive endogenous RNA in the cancer progression. The current study revealed that the overexpression of LINC00857 in LUAD tissue and cells was mainly caused by the hypomethylation of the promoter region. LINC00857 knockdown prominently reduced cell proliferation, impeded cell migration and invasion, and restrained lymph node metastasis, with enhancing radiosensitivity. The effects of LINC00857 on tumor growth were also investigated in nude mice models. Subsequently, the downstream factors, miR-486-5p and NEK2, were screened, and the putative regulatory axis was examined. Overall, the regulatory effect of methylation-mediated LINC00857 overexpression on miR-486-5p/NEK2 axis may be a new mechanism for LUAD progression.

Multicomponent, Multicavity Metallacages That Contain Different Binding Sites for Allosteric Recognition.

The encapsulation of different guest molecules by their different recognition domains of proteins leads to selective binding, catalysis, and transportation. Synthetic hosts capable of selectively binding different guests in their different cavities to mimic the function of proteins are highly desirable but challenging. Here, we report three ladder-shaped, triple-cavity metallacages prepared by multicomponent coordination-driven self-assembly. Interestingly, the porphyrin-based metallacage is capable of heteroleptic encapsulation of fullerenes (C60 or C70) and coronene using its different cavities, allowing distinct allosteric recognition of coronene upon the addition of C60 or C70. Owing to the different binding affinities of the cavities, the metallacage hosts one C60 molecule in the central cavity and two coronene units in the side cavities, while encapsulating two C70 molecules in the side cavities and one coronene molecule in the central cavity. The rational design of multicavity assemblies that enable heteroleptic encapsulation and allosteric recognition will guide the further design of advanced supramolecular constructs with tunable recognition properties.

NCOA4-mediated ferritinophagy participates in cadmium-triggered ferroptosis in spermatogonia.

Cadmium (Cd) is a common pollutant with reproductive toxicity. Our previous study revealed that Cd triggered spermatogonia ferroptosis. However, the underlying mechanisms remain unclear. Nuclear receptor coactivator 4 (NCOA4) mediates ferritinophagy and specific degradation of ferritin through lysosomes, resulting in the release of ferrous ions. Excessive autophagy can lead to ferroptosis. This study investigated the role of autophagy in Cd-triggered ferroptosis using GC-1 spermatogonial (spg) cells which exposed to CdCl2 (5 µM, 10 µM, or 20 µM) for 24 without/with CQ. The cells which transfected with Ncoa4-siRNA were used to explore the role of NCOA4-mediated ferritinophagy in Cd-triggered ferroptosis. The results revealed that Cd caused mitochondrial swelling, rupture of cristae, and vacuolar-like changes. The Cd-treated cells exhibited more autophagosomes. Simultaneously, Cd increased intracellular iron, reactive oxygen species, and malondialdehyde concentrations while decreasing glutathione content and Superoxide Dismutase-2 activity. Moreover, Cd upregulated mRNA levels of ferritinophagy-associated genes (Ncoa4, Lc3b and Fth1), as well as enhanced protein expression of NCOA4, LC3B, and FTH1. While Cd decreased the mRNA and protein expression of p62/SQSTM1. These results showed that Cd caused ferritinophagy and ferroptosis. The use of chloroquine to inhibit autophagy ameliorated Cd-induced iron overload and ferroptosis. Moreover, Ncoa4 knockdown in spermatogonia significantly reduced intracellular iron concentration and alleviated Cd-triggered ferroptosis. In conclusion, our findings demonstrate that Cd activates the ferritinophagy pathway mediated by NCOA4, resulting in iron accumulation through ferritin degradation. This causes oxidative stress, ultimately initiating ferroptosis in spermatogonia. Our results may provide new perspectives and potential strategies for preventing and treating Cd-induced reproductive toxicity.

High-Performance Materials Improve the Early Shrinkage, Early Cracking, Strength, Impermeability, and Microstructure of Manufactured Sand Concrete.

The poor early shrinkage and cracking performances of manufactured sand concrete, waste powder concrete, and recycled aggregate concrete are the main difficulties in engineering applications. To solve these problems, early shrinkage and cracking, strength, and impermeability tests were performed on high-volume stone powder manufactured sand concrete mixed with fly ash and slag powder (FS), a shrinkage-reducing agent (SRA), polyvinyl alcohol (PVA) fibers, and a superabsorbent polymer (SAP). Furthermore, the microstructures and pore structures of these concretes were revealed using nuclear magnetic resonance (NMR) and scanning electron microscopy (SEM). The results showed that the mixture of FS, SRA, PVA fibers, and SAP could effectively inhibit the shrinkage strain and cracking area of the concrete. The effect of the SAP on reducing the early shrinkage of the concrete is the greatest, and the shrinkage strain can be reduced by 76.49%. The PVA fibers had the most obvious effect on inhibiting the early cracking of the concrete, and the total cracking area was reduced by 66.91%. Significantly, the incorporation of the FS can improve the particle gradation and the pore structure and improve its compactness. The PVA fibers not only provide good carriers for cement-based materials but also enhance the bonding force between the particles inside the concrete, filling the pores inside the concrete, inhibiting the loss of water, and reducing the generation of internal microcracks. The FS and PVA can reduce the shrinkage and cracking risk and improve the strength and impermeability of the concrete. Although the SRA and SAP can reduce the shrinkage and cracking risks, it will lead to a significant decrease in the later strength and impermeability. The main reason is that the SRA leads to an increase in micropores in the matrix and microcracks near the aggregate, which are not conducive to the development of the strength and penetration resistance of the MS. Similarly, the SAP can promote the rapid formation of ettringite (Aft) at an early age and improve the early shrinkage, early cracking, and early strength of the concrete. However, with an increase in age, the residual pores, after SAP dehydration, will cause the deterioration of the concrete pore structure, resulting in the deterioration of the strength and impermeability.