Re-Designing Cellulosic Core-Shell Composite Fibers for Advanced Photothermal and Thermal-Regulating Performance.

Flexible fibers and textiles featuring photothermal conversion and storage capacities are ideal platforms for solar-energy utilization and wearable thermal management. Other than using fossil-fuel-based synthetic fibers, re-designing natural fibers with nanotechnology is a sustainable but challenging option. Herein, advanced core-shell structure fibers based on plant-based nanocelluloses are obtained using a facile co-axial wet-spinning process, which has superior photothermal and thermal-regulating performances. Besides serving as the continuous matrix, nanocelluloses also have two other important roles: dispersing agent when exfoliating molybdenum disulfide (MoS2), and stabilizer for phase change materials (PCM) in the form of Pickering emulsion. Consequently, the shell layer contains well-oriented nanocelluloses and MoS2, and the core layer contains a high content of PCM in a leak-proof encapsulated manner. Such a hierarchical cellulosic supportive structure leads to high mechanical strength (139 MPa), favorable flexibility, and large latent heat (92.0 J g-1), surpassing most previous studies. Furthermore, the corresponding woven cloth demonstrates satisfactory thermal-regulating performance, high solar-thermal conversion and storage efficiency (78.4-84.3%), and excellent long-term performance. In all, this work paves a new way to build advanced structures by assembling nanoparticles and polymers for functional composite fibers in advanced solar-energy-related applications.

Clinical characteristics and prognosis of patients with newly diagnosed primary central nervous system lymphoma: a multicentre retrospective analysis.

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

miR-200a-3p inhibits the PDGF-BB-induced proliferation of VSMCs by affecting their phenotype-associated proteins.

Accumulating evidence shows that the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) can significantly affect the long-term prognosis of coronary artery bypass grafting. This study aimed to explore the factors affecting the proliferation, migration, and phenotypic transformation of VSMCs. First, we stimulated VSMCs with different platelet-derived growth factor-BB (PDGF-BB) concentrations, analyzed the expression of phenotype-associated proteins by Western blotting, and examined cell proliferation by scratch wound healing and the 5-ethynyl-2-deoxyuridine (EdU) assay. VSMC proliferation was induced most by PDGF-BB treatment at 20 ng/mL. miR-200a-3p decreased significantly in A7r5 cells stimulated with PDGF-BB. The overexpression of miR-200a-3p reversed the downregulation of α-SMA (p < 0.001) and the upregulation of vimentin (p < 0.001) caused by PDGF-BB. CCK8 and EdU analyses showed that miR-200a-3p overexpression could inhibit PDGF-BB-induced cell proliferation (p < 0.001). However, flow cytometric analysis showed that it did not significantly increase cell apoptosis. Collectively, the overexpression of miR-200a-3p inhibited the proliferation and migration of VSMCs induced by PDGF-BB, partly by affecting phenotypic transformation-related proteins, providing a new strategy for relieving the restenosis of vein grafts.

Chitosan alleviates ovarian aging by enhancing macrophage phagocyte-mediated tissue homeostasis.

BACKGROUND: Age-related changes in the ovarian microenvironment are linked to impaired fertility in women. Macrophages play important roles in ovarian tissue homeostasis and immune surveillance. However, the impact of aging on ovarian macrophage function and ovarian homeostasis remains poorly understood. METHODS: Senescence-associated beta-galactosidase staining, immunohistochemistry, and TUNEL staining were used to assess senescence and apoptosis, respectively. Flow cytometry was employed to evaluate mitochondrial membrane potential (MMP) and apoptosis in granulosa cells lines (KGN), and macrophages phagocytosis. After a 2-month treatment with low molecular weight Chitosan (LMWC), ovarian tissues from mice were collected for comprehensive analysis. RESULTS: Compared with the liver and uterus, the ovary displayed accelerated aging in an age-dependent manner, which was accompanied by elevated levels of inflammatory factors and apoptotic cells, and impaired macrophage phagocytic activity. The aged KGN cells exhibited elevated reactive oxygen species (ROS) and apoptotic levels alongside decreased MMP. H2O2-induced aging macrophages showed reduced phagocytosis function. Moreover, there were excessive aging macrophages with impaired phagocytosis in the follicular fluid of patients with diminished ovarian reserve (DOR). Notably, LMWC administration alleviated ovarian aging by enhancing macrophage phagocytosis and promoting tissue homeostasis. CONCLUSIONS: Aging ovarian is characterized by an accumulation of aging and apoptotic granulosa cells, an inflammatory response and macrophage phagocytosis dysfunction. In turn, impaired phagocytosis of macrophage contributes to insufficient clearance of aging and apoptotic granulosa cells and the increased risk of DOR. Additionally, LMWC emerges as a potential therapeutic strategy for age-related ovarian dysfunction.

Combinatorial Synthesis of Covalent Organic Framework Particles with Hierarchical Pores and Their Catalytic Application.

Precise tailoring of the aggregation state of covalent organic frameworks (COFs) to form a hierarchical porous structure is critical to their performance and applications. Here, we report a one-pot and one-step strategy of using dynamic combinatorial chemistry to construct imine-based hollow COFs containing meso- and macropores. It relies on a direct copolymerization of three or more monomers in the presence of two monofunctional competitors. The resulting particle products possess high crystallinity and hierarchical pores, including micropores around 0.93 nm, mesopores widely distributed in the range of 3.1-32 nm, and macropores at about 500 nm, while the specific surface area could be up to 748 m2·g-1, with non-micropores accounting for 60% of the specific surface area. The particles demonstrate unique advantages in the application as nanocarriers for in situ loading of Pd catalysts at 93.8% loading efficiency in the copolymerization of ethylene and carbon monoxide. The growth and assembly of the copolymer could thus be regulated to form flower-shaped particles, efficiently suppressing the fouling of the reactor. The copolymer's weight-average molecular weight and the melting temperature are also highly improved. Our method provides a facile way of fabricating COFs with hierarchical pores for advanced applications in catalysis.

Hypoxia-mediated chemotaxis and residence of macrophage in decidua by secreting VEGFA and CCL2 during normal pregnancy.

In brief: Hypoxia is vital for the establishment of the maternal-fetal interface during early pregnancy. This study shows that decidual macrophages (dMφ) could be recruited and reside in decidua under the regulation of hypoxia/VEGFA-CCL2 axis. Abstract: Infiltration and residence of decidual macrophages (dMφ) are of great significance to pregnancy maintenance for their role in angiogenesis, placental development, and inducing immune tolerance. Besides, hypoxia has now been acknowledged as an important biological event at maternal-fetal interface in the first trimester. However, whether and how hypoxia regulates biofunctions of dMφ remain elusive. Herein, we observed increased expression of C-C motif chemokine ligand 2 (CCL2) and residence of macrophages in decidua compared to secretory-phase endometrium. Moreover, hypoxia treatment on stromal cells improved the migration and adhesion of dMφ. Mechanistically, these effects might be mediated by upregulated CCL2 and adhesion molecules (especially ICAM2 and ICAM5) on stromal cells in the presence of endogenous vascular endothelial growth factor-A (VEGFA) in hypoxia. These findings were also verified by recombinant VEGFA and indirect coculture, indicating that the interaction between stromal cells and dMφ in hypoxia condition may facilitate dMφ recruitment and residence. In conclusion, VEGFA derived from a hypoxic environment may manipulate CCL2/CCR2 and adhesion molecules to enhance the interactions between dMφ and stromal cells and thus contribute to the enrichment of macrophages in decidua early during normal pregnancy.

Covalent Organic Framework-Supported Metallocene for Ethylene Polymerization.

The loading of homogeneous catalysts with support can dramatically improve their performance in olefin polymerization. However, the challenge lies in the development of supported catalysts with well-defined pore structures and good compatibility to achieve high catalytic activity and product performance. Herein, we report the use of an emergent class of porous material-covalent organic framework material (COF) as a carrier to support metallocene catalyst-Cp2 ZrCl2 for ethylene polymerization. The COF-supported catalyst demonstrates a higher catalytic activity of 31.1×106  g mol-1 h-1 at 140 °C, compared with 11.2×106  g mol-1 h-1 for the homogenous one. The resulting polyethylene (PE) products possess higher weight-average molecular weight (Mw ) and narrower molecular weight distribution (Ð) after COF supporting, that is, Mw increases from 160 to 308 kDa and Ð drops from 3.3 to 2.2. The melting point (Tm ) is also increased by up to 5.2 °C. Moreover, the PE product possesses a characteristic filamentous microstructure and demonstrates an increased tensile strength from 19.0 to 30.7 MPa and elongation at break from 350 to 1400 % after catalyst loading. We believe that the use of COF carriers will facilitate the future development of supported catalysts for highly efficient olefin polymerization and high-performance polyolefins.

CERS4 predicts positive anti-PD-1 response and promotes immunomodulation through Rhob-mediated suppression of CD8+Tim3+ exhausted T cells in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the main malignant tumors with high mortality and short survival time. Immunotherapy has become the standard treatment for advanced NSCLC, but it has the problems of drug resistance and low response rate. Therefore, obtaining effective biomarkers to predict and enhance immune checkpoint inhibitors (ICIs) efficacy in NSCLC is important. Sphingolipid metabolism is recently found to be closely involved in tumor immunotherapy. CERS4, an important sphingolipid metabolizing enzyme, is positively correlated with the efficacy of anti-PD-1 therapy for NSCLC. Upregulation of CERS4 expression could improve the efficacy of anti-PD-1 therapy for NSCLC. High expression of CERS4 could downregulate the expression of Rhob in tumor. Significantly, the ratio of CD4+/CD8+ T cell increased and the ratio of Tim-3+/CD8+ T cell decreased in spleen and peripheral blood cells. When Rhob was knocked out, the efficacy of PD-1 mAb treatment increased, and the frequency of Tim-3+ CD8+ T cell decreased. This finding further confirmed the role of sphingolipid metabolites in regulating the immunotherapeutic function of NSCLC. These metabolites may improve the efficacy of PD-1 mAb in NSCLC by regulating the CERS4/Rhob/Tim-3 axis. Overall, this study provided a potential and effective target for predicting and improving the efficacy of ICIs for NSCLC. It also provided a new perspective for the study on the mechanisms of ICIs resistance for NSCLC.

ß-Elemene enhances erlotinib sensitivity through induction of ferroptosis by upregulating lncRNA H19 in EGFR-mutant non-small cell lung cancer.

Nearly half of all Asian non-small cell lung cancer (NSCLC) patients harbour epidermal growth factor receptor (EGFR) mutations, and first-generation EGFR tyrosine kinase inhibitors (TKIs) are one of the first-line treatments that have improved the outcomes of these patients. Unfortunately, 20% of these patients can not benefit from the treatment. The basis of this primary resistance is poorly understood. Therefore, overcoming EGFR-TKI primary resistance and maintaining the efficacy of TKIs has become a key issue. ß-Elemene, a sesquiterpene compound extracted from Curcuma aromatica Salisb. (wenyujing), has shown potent antitumor effects. In this research, we found that ß-elemene combined with erlotinib enhanced the cytotoxicity of erlotinib to primary EGFR-TKI-resistant NSCLC cells with EGFR mutations and that ferroptosis was involved in the antitumor effect of the combination treatment. We found that lncRNA H19 was significantly downregulated in primary EGFR-TKI-resistant NSCLC cell lines and was upregulated by the combination treatment. Overexpression or knockdown of H19 conferred sensitivity or resistance to erlotinib, respectively, in both in vitro and in vivo studies. The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that ß-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.

Mechanistic Understanding of Efficient Polyethylene Hydrocracking over Two-Dimensional Platinum-Anchored Tungsten Trioxide.

Chemical upcycling of polyethylene (PE) can convert plastic waste into valuable resources. However, engineering a catalyst that allows PE decomposition at low temperatures with high activity remains a significant challenge. Herein, we anchored 0.2 wt.% platinum (Pt) on defective two-dimensional tungsten trioxide (2D WO3 ) nanosheets and achieved hydrocracking of high-density polyethylene (HDPE) waste at 200-250 °C with a liquid fuel (C5-18 ) formation rate up to 1456 gproducts ⋅ gmetal species -1 ⋅ h-1 . The reaction pathway over the bifunctional 2D Pt/WO3 is elucidated by quasi-operando transmission infrared spectroscopy, where (I) well-dispersed Pt immobilized on 2D WO3 nanosheets trigger the dissociation of hydrogen; (II) adsorption of PE and activation of C-C cleavage on WO3 are through the formation of C=O/C=C intermediates; (III) intermediates are converted to alkane products by the dissociated H. Our study directly illustrates the synergistic role of bifunctional Pt/WO3 catalyst in the hydrocracking of HDPE, paving the way for the development of high-performance catalysts with optimized chemical and morphological properties.

Oxymatrine Alleviates Hyperglycemic Cerebral Ischemia/Reperfusion Injury via Protecting Microvessel.

Hyperglycemia aggravates cerebral ischemia/reperfusion (I/R) injury via vascular injury. There is still a lack of effective pharmaceutical preparations for cerebral I/R injury under hyperglycemia. This study aimed to investigate the effects of oxymatrine (OMT) on hyperglycemia-exacerbated cerebral I/R injury in vitro and in vivo. The middle cerebral artery occlusion (MCAO) and reperfusion was established in the rats under hyperglycemia. Meanwhile, oxygen-glucose deprivation and reoxygenation (OGD/R) with high glucose was used as an in vitro model of hyperglycemic cerebral I/R injury. The results showed that the neurological deficit score, mortality, infarct volume and penumbra apoptosis in hyperglycemia group were significantly higher than those in normal glucose group. OMT pre-treated obviously reduced the degree of neurological deficit, mortality, infarct volume, improve cerebral blood flow after I/R in rats with hyperglycemia, and increase the survival rate of human brain microvascular endothelial cells (HBMECs) in high glucose and OGD/R group. OMT significantly improved the ultrastructure changes of endothelial cells, and maintain the migration and angiogenesis potency of HBMECs in high glucose and OGD/R group. OMT obviously alleviated the down-regulating CD31 and CD105 expression in cerebral microvessels caused by hyperglycemia. It is concluded that OMT treatment might alleviate cerebral I/R injury under hyperglycemia via protecting microvessels.

The anti-obesity and gut microbiota modulating effects of taxifolin in C57BL/6J mice fed with a high-fat diet.

BACKGROUND: Taxifolin is a natural dihydroflavonol found in many plants and health products. In the present study, its anti-obesity and gut microbiota modulating effects were studied. C57BL/6J mice were fed with a high-fat diet (HFD) supplemented with taxifolin (0, 0.5 and 1 mg mL-1 , respectively) in drinking water for 15 weeks. RESULTS: Taxifolin supplementation showed no influence on food and water intake. However, it decreased body weight gain, inhibited fat accumulation, and decreased total cholesterol and triacylglycerol level in mice liver. Taxifolin enhanced superoxide dismutase (SOD) activity in mice liver, which in turn protected the liver from lipid peroxidation damage. It also improved insulin resistance in obese mice. Metagenomic analysis of bacterial 16S rRNA demonstrated that HFD decreased gut microbiota diversity and caused dysbiosis. However, taxifolin improved the gut microbiota diversity and decreased the Firmicutes/Bacteroidetes ratio. In particular, it inhibited Proteobacteria from blooming, this being a signature of dysbiosis in gut microbiota. CONCLUSION: Taxifolin ameliorated the symptoms of obesity, hepatic steatosis, lipid peroxidation, insulin resistance, and gut microbiota dysbiosis in HFD fed C57BL/6J mice. © 2021 Society of Chemical Industry.

Network pharmacology and in vitro experimental verification to explore the mechanism of Sanhua decoction in the treatment of ischaemic stroke.

CONTEXT: Stroke is an illness with high morbidity, disability and mortality that presents a major clinical challenge. Sanhua decoction (SHD) has been widely used to treat ischaemic stroke in the clinic. However, the potential mechanism of SHD remains unknown. OBJECTIVE: To elucidate the multitarget mechanism of SHD in ischaemic stroke through network pharmacology and bioinformatics analyses. MATERIALS AND METHODS: Network pharmacology and experimental validation approach was used to investigate the bioactive ingredients, critical targets and potential mechanisms of SHD against ischaemic stroke. Four herbal names of SHD, 'ischemic stroke' or 'stroke' was used as a keyword to search the relevant databases. SH-SY5Y cells were treated with various concentrations of SHD (12.5, 25, 50 or 100 µg/mL) for 4 h, exposed to oxygen and glucose deprivation (OGD) for 1 h, then reoxygenation for 24 h. The cell viability was detected by MTT, the lactate dehydrogenase (LDH) was evaluated by ELISA, and protein expression was detected by western blots. RESULTS: SHD treatment increased the survival rate from 65.9 ± 4.3 to 85.56 ± 5.7%. The median effective dose (ED50) was 47.1 µg/mL, the LDH decreased from 288.0 ± 12.0 to 122.8 ± 9.1 U/L and the cell apoptosis rate decreased from 33.6 ± 1.8 to 16.3 ± 1.2%. Western blot analysis revealed that SHD increased the levels of p-PI3k, p-Akt and p-CREB1, and decreased the expression of TNF-α and IL-6. DISCUSSION AND CONCLUSIONS: This study suggests that SHD protects against cerebral ischaemic injury via regulation of the PI3K/Akt/CREB1 and TNF pathways.

The Viral Load of Human Cytomegalovirus Infection in Children following Hematopoietic Stem Cell Transplant by Chip Digital PCR.

Objective: To detect viral load in human cytomegalovirus (HCMV) infection children after hematopoietic stem cell transplant (HSCT) by chip digital PCR (cdPCR). Methods: The plasmid pUC57-UL83 containing the HCMV-UL83 gene and HCMV AD169 strain were used to evaluate the sensitivity of cdPCR. Either HSV-1, HSV-2, VZV, EBV, HHV-6, or HHV-7 was used to evaluate the specificity of HCMV cdPCR. The cdPCR was compared with quantitative PCR (qPCR) by detecting HCMV infection in 125 children's whole blood samples following HSCT. Results: The limit of detection (LOD) of HCMV cdPCR was 103 copies/ml and the qPCR LOD was 297 copies/ml for plasmid pUC57-UL83. The result of HCMV cdPCR was 146 copies/ml for the HCMV AD169 strain, indicating that the sensitivity of cdPCR was higher than that of qPCR. There is no cross-reaction between HCMV cdPCR and other herpes viruses. The incidence of HCMV infection was 30.40% in 125 children following HSCT by cdPCR. The range of the HCMV viral load was from 107 copies/ml to 6600 copies/ml by cdPCR. Conclusions: cdPCR is more sensitive than qPCR for detecting HCMV viral load. Furthermore, the cdPCR could be used to detect the viral load of HCMV infection before or after HSCT in children.

[Receiving Human Immunodeficiency Virus Serostatus Disclosure from Male Sexual Partners and Related Factors among Men Who Have Sex with Men Aged 50 and Above].

Objective To investigate the rate and correlates of receiving human immunodeficiency virus(HIV) serostatus disclosure from their most recent male sexual partners among men who have sex with men(MSM) aged 50 and above. Methods With a geosocial networking application,we recruited participants through online convenience sampling to collect the demographic variables,behavioral information,receiving HIV serostatus disclosure,etc.Univariate and multivariate analyses were performed to interpret the associated factors of receiving HIV serostatus disclosure. Results Overall,38.4%(398/1037) of participants received HIV serostatus disclosure from their most recent male sexual partners.The multivariable analysis demonstrated that the following populations were less likely to receive HIV serostatus disclosure from their most recent male sexual partners:participants with junior high school degree or below(OR=0.660,95%CI=0.473-0.922, P=0.015) compared to those with senior high school degree or above;participants unemployed(OR=0.537,95%CI=0.322-0.896, P=0.017) and employed(OR=0.663,95%CI=0.466-0.944, P=0.022) compared to those retired;participants without knowledge about HIV or acquired immune deficiency syndrome(AIDS) compared to those with knowledge about HIV/AIDS(OR=0.636,95%CI=0.466-0.868, P=0.004);participants having ≥2 male sexual partners in the last year(OR=0.433,95%CI=0.320-0.586, P<0.001) compared to those having none or one male sexual partner;participants never been tested for HIV(OR=0.544,95%CI=0.403-0.734, P<0.001) compared to those ever been tested for HIV;participants ever been diagnosed to have sexually transmitted infection(STI)(OR=0.472,95%CI=0.349-0.637, P<0.001) compared to those never diagnosed to have STI;and participants with higher level of HIV stigma(OR=0.742,95%CI=0.604-0.912, P=0.005). Conclusions Our findings indicated that the MSM aged 50 and above had low possibility of receiving HIV serostatus disclosure from the most recent male sexual partners.Education,employment status,number of sexual partners,HIV/AIDS-related knowledge,HIV testing behaviors,STI infection history,and HIV stigma contributed to this result.

[Mental Health Status and Its Influencing Factors among College Students during the Epidemic of Coronavirus Disease 2019:A Multi-center Cross-sectional Study].

Objective To measure the prevalence of mental health symptoms and identify the associated factors among college students at the beginning of coronavirus disease 2019(COVID-19)outbreak in China. Methods We carried out a multi-center cross-sectional study via snowball sampling and convenience sampling of the college students in different areas of China.The rates of self-reported depression,anxiety,and stress and post-traumatic stress disorder(PTSD)were assessed via the 21-item Depression-Anxiety-Stress Scale(DASS-21)and the 6-item Impact of Event Scale-Revised(IES-6),respectively.Covariates included sociodemographic characteristics,health-related data,and information of the social environment.Data pertaining to mental health service seeking were also collected.Multivariate Logistic regression analyses were performed to identify the risk factors. Results A total of 3641 valid questionnaires were collected from college students.At the beginning of the COVID-19 outbreak,535(14.69%)students had negative emotions,among which 402(11.04%),381(10.49%),and 171(4.90%)students had the symptoms of depression,anxiety,and stress,respectively.Meanwhile,1245(34.19%)college students had PTSD.Among the risk factors identified,male gender was associated with a lower likelihood of reporting depression symptoms(AOR=0.755,P=0.037],and medical students were at higher risk of depression and stress symptoms than liberal arts students(AOR=1.497,P=0.003;AOR=1.494,P=0.045).Family support was associated with lower risks of negative emotions and PTSD in college students(AOR=0.918,P<0.001;AOR=0.913,P<0.001;AOR=0.899,P<0.001;AOR=0.971,P=0.021). Conclusions College students were more sensitive to public health emergencies,and the incidence of negative emotions and PTSD was significantly higher than that before the outbreak of COVID-19.More attention should be paid to female college students who were more likely to develop negative emotions.We should strengthen positive and proper propaganda via mass media and help college students understand the situation and impact of COVID-19.Furthermore,we should enhance family support for college students.The government and relevant agencies need to provide appropriate mental health services to the students under similar circumstances to avoid the deterioration of their mental well-being.

Investigation of hub genes and immune status in heart transplant rejection using endomyocardial biopsies.

T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) are severe post-transplantation complications for heart transplantation (HTx), whose molecular and immunological pathogenesis remains unclear. In the present study, the mRNA microarray data set GSE124897 containing 645 stable, 52 TCMR and 144 ABMR endomyocardial biopsies was obtained to screen for differentially expressed genes (DEGs) between rejected and stable HTx samples and to investigate immune cell infiltration. Functional enrichment analyses indicated roles of the DEGs primarily in immune-related mechanisms. Protein-protein interaction networks were then constructed, and ICAM1, CD44, HLA-A and HLA-B were identified as hub genes using the maximal clique centrality method. Immune cell infiltration analysis revealed differences in adaptive and innate immune cell populations between TCMR, ABMR and stable HTx samples. Additionally, hub gene expression levels significantly correlated with the degree and composition of immune cell infiltration in HTx rejection samples. Furthermore, drug-gene interactions were constructed, and 12 FDA-approved drugs were predicted to target hub genes. Finally, an external GSE2596 data set was used to validate the expression of the hub genes, and ROC curves indicated all four hub genes had promising diagnostic value for HTx rejection. This study provides a comprehensive perspective of molecular and immunological regulatory mechanisms underlying HTx rejection.

Toward Covalent Organic Framework Metastructures.

The bottom-up assembly of periodically ordered structures provides a scalable way for producing metastructured materials with exotic optical and mechanical properties. However, direct self-assembly of small molecules into such metastructures beyond the nanoscale remains an unresolved issue. Here we demonstrate that metastructured assemblies of two-dimensional (2D) polymers, specifically 2D covalent organic frameworks (COFs), can be directly synthesized in solution. We applied 2D COF monomer polycondensation to prepare flower-shaped particles consisting of highly crystalline "petals" with sizes larger than 20 µm. The petal comprises periodically arranged COF nanoflake units with tunable lengths of 490-850 nm, thicknesses about 20 nm, interflake spacing around 14 nm, and Hermans orientation factors up to 0.998. Such a metastructure is mechanically robust and remains almost intact even after full pyrolysis at 900 °C. It also demonstrates unique birefringence and polarization-dependent resonances under visible-near-infrared light not observed in its constituents, 2D COF polycrystals, and with well-defined nanopores of 1.8 nm and the high surface area of 1576 m2/g. Such metastructured particles with nanopores are well-suited as novel particulate optical devices for collecting and storing information about their surroundings that can be easily read out by polarization imaging with high sensitivity, as demonstrated by their explosive detection and anticounterfeiting applications. Self-assembly of 2D polymers into metastructures may become an important method for developing functional materials with unprecedented properties and extensive applications.

The influence of pre-existing hypertension on coronavirus disease 2019 patients.

Hypertension represents one of the most common pre-existing conditions and comorbidities in Coronavirus disease 2019 (COVID-19) patients. To explore whether hypertension serves as a risk factor for disease severity, a multi-centre, retrospective study was conducted in COVID-19 patients. A total of 498 consecutively hospitalised patients with lab-confirmed COVID-19 in China were enrolled in this cohort. Using logistic regression, we assessed the association between hypertension and the likelihood of severe illness with adjustment for confounders. We observed that more than 16% of the enrolled patients exhibited pre-existing hypertension on admission. More severe COVID-19 cases occurred in individuals with hypertension than those without hypertension (21% vs. 10%, P = 0.007). Hypertension associated with the increased risk of severe illness, which was not modified by other demographic factors, such as age, sex, hospital geological location and blood pressure levels on admission. More attention and treatment should be offered to patients with underlying hypertension, who usually are older, have more comorbidities and more susceptible to cardiac complications.

A novel miR-200c/c-myc negative regulatory feedback loop is essential to the EMT process, CSC biology and drug sensitivity in nasopharyngeal cancer.

Overexpression of the c-Myc oncogene has been implicated in cancer stem cell - like (CSC) phenotypes and epithelial-to-mesenchymal transition (EMT) in cancer. However, the underlying molecular mechanism by which c-Myc regulates EMT and CSC potential in remains unclear. In the present study, we showed that the expression of c-Myc protein is inversely correlated with microRNA (miR)-200c expression in primary tumor samples from nasopharyngeal cancer (NPC) patients. We further demonstrated that Myc and miR-200c negatively regulate the expression each other in NPC cell lines. c-Myc transcriptionally repressed expression of miR-200c by directly binding to two E-box sites located within a 1 kb segment upstream of TSS of the miR-200c. In addition, miR-200c post-transcriptionally repressed expression of c-Myc by binding to its 3'-untranslated region, suggesting the existence of a negative feedback loop between Myc and miR-200c. Overexpression of c-Myc interfered with this feedback loop and activated the EMT program, induced CSC phenotypes, and enhanced drug sensitivity, whereas miR-200c could counteract these biological effects of c-Myc. Our results provide a novel mechanism governing c-Myc and miR-200c expression and indicate that either targeting c-Myc or restoring miR-200c expression would be a promising approach to overcome oncogenic role of c-Myc in NPC.