Bilayer Intelligent Omni-Surface-Assisted Full-Duplex Systems: Simultaneous Self-Interference Cancellation and Sum Rate Maximization.

Recently, reconfigurable intelligent surfaces (RISs) have attracted increasing attentions in the design of full-duplex (FD) systems due to their novel capability of propagation environment reconfiguration. However, in conventional RIS-assisted FD systems, the beamforming for self-interference cancellation (SIC) and sum rate maximization (SRM) are highly coupled during RIS optimization, which significantly degrades the system performance. To tackle this issue, we exploit a novel bilayer intelligent omni-surface (BIOS) structure in FD systems. Compared with the conventional RIS designs, the BIOS provides independent beams on both sides, thus enabling more flexible achievement of SRM and SIC. For the BIOS-assisted FD system, we first formulate an optimization problem to achieve SRM and efficient SIC simultaneously. Then, we exploit the relationship between the SRM and mean square error (MSE), and propose a weighted MSE minimization with SIC algorithm to solve the problem. Specifically, we jointly design the beamforming at the base station and the BIOS with manifold optimization while guaranteeing an SIC constraint. Furthermore, we theoretically derive a lower band for the BIOS size required for efficient SIC in FD systems. Simulation results indicate that the BIOS outperforms the conventional RIS designs in FD systems, and verify the accuracy of the derived lower bound for the BIOS size.

One year clinical outcome of dual anti-platelet therapy with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm: A meta-analysis.

BACKGROUND: The use of stents to treat un-ruptured intracranial aneurysms was first approved in the year 2002 in the United States as a Humanitarian Device Exemption. Antiplatelet therapy is mandatory following stent placement. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been the first line agents for the prevention of thromboembolic events following neuro-endovascular procedures. However, clopidogrel hypo-responsiveness has often been observed. In this analysis, we aimed to systematically compare one year clinical outcome of DAPT with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm. METHODS: Online electronic databases were searched from June 2023 till July 2023 for relevant studies which compared DAPT with ticagrelor or clopidogrel for endovascular intervention in patients with intracranial aneurysm. The endpoints which were analyzed were classified into thromboembolic and hemorrhagic events. A fixed and a random effect statistical model were used during data analysis respectively. Risk ratio (RR) with 95 % confidence interval (CI) was used to represent the data following analysis. RESULTS: Five studies with a total number of 893 participants were included in this analysis. Three hundred and fifty eight (358) participants were assigned to the ticagrelor group whereas 535 participants were assigned to clopidogrel group. Participants' enrollment period ranged from the year 2009 to 2019. Our results showed that during a mean follow-up time period of one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events with RR: 0.33, 95 % CI: 0.16 - 0.68; P = 0.003. In addition, at one year, DAPT with ticagrelor was not associated with any increase in hemorrhagic events (RR: 0.66, 95 % CI: 0.29 - 1.50; P = 0.32) when compared to DAPT with clopidogrel. CONCLUSION: At one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events without any increase in hemorrhagic events when compared to clopidogrel associated DAPT for endovascular intervention of patients with intracranial aneurysm. However, even though ticagrelor-associated DAPT use appeared to be more effective and safe, this hypothesis should only be confirmed in larger upcoming trials.

The effect of silica exposure on the risk of lung cancer: A meta-analysis.

Lung cancer is an incurable disease with an increased mortality rate caused by the inhalation of dust-containing crystalline silica particles. Silica exposure is one of the most important occupational hazards in the world. Whether the association between silica exposure and lung cancer is because of the fibrotic process or to the effect of respirable silica itself is unclear. The International Agency for Research on Cancer (IARC) classified silica as a human lung carcinogen. The opinion of lung cancer is a question that has been addressed in this review. Three electronic databases, including MEDLINE, Scopus, and Web of Science, were used to search for relevant literature from 2000 to 2022. To evaluate the relationship between exposure to silica and developing lung cancer, we performed a meta-analysis using the random-effects model. For each study, the overall odds ratio (OR), relative risk (RR) with 95% confidence intervals (CI), and p values were calculated. An extensive database search resulted in the selection of 20 (case-control and nested case-control studies were selected) out of 527 studies. Among the 20 selected studies, 7 studies showed a significant association between silica exposure and an increased risk of lung cancer. Further analysis showed that among the selected studies, six studies showed a significant correlation between combined exposure to silica and smoking with an increased risk of lung cancer. The data from the present study showed that smoking habits increased the impact of silica exposure on the initiation of lung carcinogenesis in exposed workers.

Targeting cholesterol biosynthesis promotes anti-tumor immunity by inhibiting long noncoding RNA SNHG29-mediated YAP activation.

Anti-tumor immunity through checkpoint inhibitors, specifically anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interaction, is a promising approach for cancer therapy. However, as early clinical trials indicate that colorectal cancers (CRCs) do not respond well to immune-checkpoint therapies, new effective immunotherapy approaches to CRC warrant further study. Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (CoA) reductase (HMGCR), the rate-limiting enzyme of the mevalonate (MVA) pathway for the cholesterol biosynthesis. However, little is known about the functions of simvastatin in the regulation of immune checkpoints or long noncoding RNA (lncRNA)-mediated immunoregulation in cancer. Here, we found that simvastatin inhibited PD-L1 expression and promoted anti-tumor immunity via suppressing the expression of lncRNA SNHG29. Interestingly, SNHG29 interacted with YAP and inhibited phosphorylation and ubiquitination-mediated protein degradation of YAP, thereby facilitating downregulation of PD-L1 transcriptionally. Patient-derived tumor xenograft (PDX) models and the clinicopathological analysis in samples from CRC patients further supported the role of the lncRNA SNHG29-mediated PD-L1 signaling axis in tumor microenvironment reprogramming. Collectively, our study uncovers simvastatin as a potential therapeutic drug for immunotherapy in CRC, which suppresses lncRNA SNHG29-mediated YAP activation and promotes anti-tumor immunity by inhibiting PD-L1 expression.

Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m6A reader YTHDF3.

BACKGROUND: YAP activation is crucial for cancer development including colorectal cancer (CRC). Nevertheless, it remains unclear whether N6-Methyladenosine (m6A) modified transcripts of long noncoding RNAs (lncRNAs) can regulate YAP activation in cancer progression. We investigated the functional link between lncRNAs and the m6A modification in YAP signaling and CRC progression. METHODS: YAP interacting lncRNAs were screened by RIP-sequencing, RNA FISH and immunofluorescence co-staining assays. Interaction between YAP and lncRNA GAS5 was studied by biochemical methods. MeRIP-sequencing combined with lncRNA-sequencing were used to identify the m6A modified targets of YTHDF3 in CRC. Gain-of-function and Loss-of-function analysis were performed to measure the function of GAS5-YAP-YTHDF3 axis in CRC progression in vitro and in vivo. RESULTS: GAS5 directly interacts with WW domain of YAP to facilitate translocation of endogenous YAP from the nucleus to the cytoplasm and promotes phosphorylation and subsequently ubiquitin-mediated degradation of YAP to inhibit CRC progression in vitro and in vivo. Notably, we demonstrate the m6A reader YTHDF3 not only a novel target of YAP but also a key player in YAP signaling by facilitating m6A-modified lncRNA GAS5 degradation, which profile a new insight into CRC progression. Clinically, lncRNA GAS5 expressions is negatively correlated with YAP and YTHDF3 protein levels in tumors from CRC patients. CONCLUSIONS: Our study uncovers a negative functional loop of lncRNA GAS5-YAP-YTHDF3 axis, and identifies a new mechanism for m6A-induced decay of GAS5 on YAP signaling in progression of CRC which may offer a promising approach for CRC treatment.

Hypothermia alleviated LPS-induced acute lung injury in Rat models through TLR2/MyD88 pathway.

Acute lung injury (ALI) is a common clinical syndrome in ICU departments with high mortality. The pathology of ALI is still not clear and there is no specific and efficient treatment against ALI. In this study, we established ALI rat model through lipopolysaccharide administration. We found that hypothermia therapy led to significant improvement in oxygenation index, edema formation and pathological score, demonstrating that hypothermia is beneficial to the recovery of lung function and alleviation of lung injury. Besides, hypothermia resulted in a decrease in plasminogen activator inhibitor-1(PAI-1) concentration, showing the inflammation was partially inhibited. This was also confirmed by a decrease in TNF-α mRNA and protein level in hypothermia group. The effect of hypothermia was mediated by TLR2/MyD88 signaling, which led to the alteration in NF-κB p65 level. Collectively, this study indicated that hypothermia therapy was potentially an efficient therapy against ALI.

Macrolactins from Marine-Derived Bacillus subtilis B5 Bacteria as Inhibitors of Inducible Nitric Oxide and Cytokines Expression.

In order to find new natural products with anti-inflammatory activity, chemical investigation of a 3000-meter deep-sea sediment derived bacteria Bacillus subtilis B5 was carried out. A new macrolactin derivative was isolated and identified as 7,13-epoxyl-macrolactin A (1). Owing to the existence of the epoxy ring, 1 exhibited a significant inhibitory effect on the expression of inducible nitric oxide and cytokines, compared with previously isolated known macrolactins (2-5). Real-time Polymerase Chain Reaction (PCR) analysis showed that the new compound significantly inhibited the mRNA expressions of inducible nitric oxide synthase (iNOS), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Reverse transcription-PCR analysis demonstrated that the new compound reduced the mRNA expression level of IL-1ß in a concentration-dependent manner.

Developing high performance biodegradable film based on crosslinking of cellulose acetate and tannin using caprolactone.

The use of metal catalysts during the production process of cellulose acetate (CA) film can have an impact on the environment, due to their toxicity. Diphenyl phosphate (DPP) was used instead of toxic metal catalyst to react with cellulose acetate, tannin (T) and caprolactone (CL) for preparation of cellulose acetate-caprolactone-tannin (CA-CL-T) film. The results show that DPP can produce a cross-linked network structure composed of tannin, caprolactone and cellulose acetate. The maximum molecular weight reached 113,260 Da. The introduction of tannin and caprolactone into cellulose acetate caused the resulting CA-CL-T film acquire excellent strengthening/toughening effect, in which a tensile strength of 23 MPa and elongation at break of 18 % were attained. More importantly, the resistance of the film to UV radiation was significantly improved with the tannin addition, which was corroborated by the CA-CL-T film still exhibiting a tensile strength of 13 MPa and elongation at break around 13 % after continuous exposure to UV radiation for 9 days. On the other hand, the insertion of caprolactone provoked enhancement of the overall moisture resistance. Five days treatment of the films with Penicillium sp. induced gradual drop in quality, indicating the CA-CL-T film show response to biodegradation. In all, the effective crosslinking between the components of the developed material is responsible for the acquired set of these distinct characteristics.

Sysmex XN-HPC: study of reference intervals and clinical decision limits in healthy allogeneic donors mobilised with G-CSF.

The Sysmex XN series haematopoietic progenitor cell (XN-HPC) is a novel tool for assessing stem cell yield before allogeneic haematopoietic stem cell transplantation. This study aimed to establish a reference interval (RI) for XN-HPC in peripheral blood allogeneic transplant donors following granulocyte colony-stimulating factor (G-CSF) stimulation and determine its clinical significance. All specimens were analysed using Sysmex XN-20. Samples were collected and analysed using non-parametric percentile methods to define the RIs. Quantile regression was used to explore the dependency of the RIs on sex and age. Samples were included in clinical decision limits for apheresis based on receiver operating characteristic curve analysis. The non-parametrically estimated RI for XN-HPC was 623.50 (90% confidence interval [CI90%] 510.00-657.00) to 4,144.28 (CI90% 3,761.00-4,547.00). The RIs for the XN-HPC were not age-dependent but were sex-dependent. The RI for males was 648.40 (CI90% 582.00-709.00)-4,502.60 (CI90% 4,046.00-5,219.00) and for females was 490.90 (CI90% 311.00-652.00)-3,096.90 (CI90% 2,749.00-3,782.00). Comparisons based on XN-HPC values between the poor and less-than-optimal groups, good and less-than-optimal groups, and good and non-good groups had areas under the curve of 0.794 (P < 0.001), 0.768 (P < 0.001), and 0.806 (P < 0.001), respectively, indicating a good predictive value for mobilisation effectiveness. XN-HPC data exceeding 3974 × 106/L suggested that a sufficient number of stem cells could be collected clinically. Values > 5318 < 106/L indicated 100% mobilisation effectiveness. We established an RI for XN-HPC in peripheral blood allogeneic transplant donors following G-CSF stimulation and determined clinical decision thresholds for mobilisation efficiency.

[Clinical features and epidemiological trend of diabetic ketosis in patients admitted to West China Hospital].

OBJECTIVE: To evaluate the clinical features and epidemiological trend of diabetes ketosis (DK) in patients admitted to West China Hospital. METHODS: We reviewed medical records of diabetic patients with DK who were admitted to West China Hospital from 1997 to 2005. Their clinical and laboratory data were analysed with SAS 9.0. RESULTS: From 1997 to 2005, the proportion of diabetic patients with DK increased by 0.12% annually. The proportion of provoked DK patients (who had a clinically evident precipitating factor) in those with DK remained stable; whereas the proportion of T1D patients in those with DK declined by 2.00% annually and the proportion of ketosis prone obesity diabetes (KPD) in those with DK increased by 2.27% annually. The KPD patients displayed a striking male predominance (2.31:1, male:female) and were diagnosed at an older age compared with those with T1D [(46.3 +/- 12.9) yr. vs. (28.9 +/- 14.7) yr.]. The KPD patients were more likely to have a strong family history of diabetes and a better beta-cell function reserve, and be accompanied with dyslipidemia (52.7%), hypertension (23.3%), fatty liver (10.1%) and hyperuricemia/gout (8. 5%) compared with those with T1D. CONCLUSION: In recent years the proportion of KPD patients in the hospitalized DK patients is increasing. With different characteristics compared with typical T1D, KPD might belong to a subgroup of T2D.

Facile Fabrication of High-Performance Composite Films Comprising Polyvinyl Alcohol as Matrix and Phenolic Tree Extracts.

Given that tree extracts such as tannin and lignin can be efficiently used as modifying materials, this helps to verify the global trend of energy saving and environment protection. Thus, bio-based biodegradable composite film incorporating tannin and lignin as additives, together with polyvinyl alcohol (PVOH) as a matrix (denoted TLP), was prepared. Its easy preparation process endows it with high industrial value in comparison to some bio-based films with complex preparation process such as cellulose-based films. Furthermore, imaging with scanning electron microscopy (SEM) shows that the surface of tannin- and lignin-modified polyvinyl alcohol film was smooth, free of pores or cracks. Moreover, the addition of lignin and tannin improved the tensile strength of the film, which reached 31.3 MPa as indicated by mechanical characterization. This was accounted for by using Fourier transform infrared (FTIR) and electrospray ionization mass (ESI-MS) spectroscopy, which showed that the physical blending of lignin and tannin with PVOH was accompanied by chemical interactions that gave rise to weakening of the prevailing hydrogen bonding in PVOH film. In consequence, the addition of tannin and lignin acquired the composite film good resistance against the light in the ultraviolet and visible range (UV-VL). Furthermore, the film exhibited biodegradability with a mass loss about 4.22% when contaminated with Penicillium sp. for 12 days.

Expression Mapping and Functional Analysis of Orphan G-Protein-Coupled Receptor GPR158 in the Adult Mouse Brain Using a GPR158 Transgenic Mouse.

Aberrant expression of G-protein-coupled receptor 158 (GPR158) has been reported to be inextricably linked to a variety of diseases affecting the central nervous system, including Alzheimer's disease (AD), depression, intraocular pressure, and glioma, but the underlying mechanism remains elusive due to a lack of biological and pharmacological tools to elaborate its preferential cellular distribution and molecular interaction network. To assess the cellular localization, expression, and function of GPR158, we generated an epitope-tagged GPR158 mouse model (GPR158Tag) that exhibited normal motor, cognitive, and social behavior, no deficiencies in social memory, and no anxiety-like behavior compared to C57BL/6J control mice at P60. Using immunofluorescence, we found that GPR158+ cells were distributed in several brain regions including the cerebral cortex, hippocampus, cerebellum, and caudate putamen. Next, using the cerebral cortex of the adult GPR158Tag mice as a representative region, we found that GPR158 was only expressed in neurons, and not in microglia, oligodendrocytes, or astrocytes. Remarkably, the majority of GPR158 was enriched in Camk2a+ neurons whilst limited expression was found in PV+ interneurons. Concomitant 3D co-localization analysis revealed that GPR158 was mainly distributed in the postsynaptic membrane, but with a small portion in the presynaptic membrane. Lastly, via mass spectrometry analysis, we identified proteins that may interact with GPR158, and the relevant enrichment pathways were consistent with the immunofluorescence findings. RNA-seq analysis of the cerebral cortex of the GPR158-/- mice showed that GPR158 and its putative interacting proteins are involved in the chloride channel complex and synaptic vesicle membrane composition. Using these GPR158Tag mice, we were able to accurately label GPR158 and uncover its fundamental function in synaptic vesicle function and memory. Thus, this model will be a useful tool for subsequent biological, pharmacological, and electrophysiological studies related to GPR158.

A Quasi-2D Polypyrrole Film with Band-Like Transport Behavior and High Charge-Carrier Mobility.

Quasi-2D (q2D) conjugated polymers (CPs) are polymers that consist of linear CP chains assembled through non-covalent interactions to form a layered structure. In this work, the synthesis of a novel crystalline q2D polypyrrole (q2DPPy) film at the air/H2 SO4 (95%) interface is reported. The unique interfacial environment facilitates chain extension, prevents disorder, and results in a crystalline, layered assembly of protonated quinoidal chains with a fully extended conformation in its crystalline domains. This unique structure features highly delocalized π-electron systems within the extended chains, which is responsible for the low effective mass and narrow electronic bandgap. Thus, the temperature-dependent charge-transport properties of q2DPPy are investigated using the van der Pauw (vdP) method and terahertz time-domain spectroscopy (THz-TDS). The vdP method reveals that the q2DPPy film exhibits a semiconducting behavior with a thermally activated hopping mechanism in long-range transport between the electrodes. Conversely, THz-TDS reveals a band-like transport, indicating intrinsic charge transport up to a record short-range high THz mobility of ≈107.1 cm2 V-1 s-1 .

PERK-Mediated Cholesterol Excretion from IDH Mutant Glioma Determines Anti-Tumoral Polarization of Microglia.

Isocitrate dehydrogenase (IDH) mutation, a known pathologic classifier, initiates metabolic reprogramming in glioma cells and has been linked to the reaction status of glioma-associated microglia/macrophages (GAMs). However, it remains unclear how IDH genotypes contribute to GAM phenotypes. Here, it is demonstrated that gliomas expressing mutant IDH determine M1-like polarization of GAMs, while archetypal IDH induces M2-like polarization. Intriguingly, IDH-mutant gliomas secrete excess cholesterol, resulting in cholesterol-rich, pro-inflammatory GAMs without altering their cholesterol biosynthesis, and simultaneously exhibiting low levels of tumoral cholesterol due to expression remodeling of cholesterol transport molecules, particularly upregulation of ABCA1 and downregulation of LDLR. Mechanistically, a miR-19a/LDLR axis-mediated novel post-transcriptional regulation of cholesterol uptake is identified, modulated by IDH mutation, and influencing tumor cell proliferation and invasion. IDH mutation-induced PERK activation enhances cholesterol export from glioma cells via the miR-19a/LDLR axis and ABCA1/APOE upregulation. Further, a synthetic PERK activator, CCT020312 is introduced, which markedly stimulates cholesterol efflux from IDH wild-type glioma cells, induces M1-like polarization of GAMs, and consequently suppresses glioma cell invasion. The findings reveal an essential role of the PERK/miR-19a/LDLR signaling pathway in orchestrating gliomal cholesterol transport and the subsequent phenotypes of GAMs, thereby highlighting a novel potential target pathway for glioma therapy.

Tannin-Epoxidized Soybean Oil as Bio-Based Resin for Fabrication of Grinding Wheel.

Formaldehyde-free epoxidized soybean oil-based resin has been prepared under acidic conditions by co-condensation of the epoxidized soybean oil and condensed tannin originating from agricultural and forestry sources as the main raw materials, whereas 1,6-hexanediamine was employed as a cross-linking agent. Fourier transform infrared spectroscopy (FTIR) and electrospray ionization (ESI) corroborated that tannin and epoxidized soybean oil underwent crosslinking under acidic conditions supported by hexamethylenediamine. A bio-based grinding wheel was fabricated by formulation of the developed resin with wood powder as source of grinding particles. The appearance, hardness, compressive strength and wear resistance of the resulting grinding wheel were studied. The results have shown that the grinding wheel possesses a smooth surface with no bubbles or cracks, and its hardness and wear resistance were greater than that of a phenolic resin-based grinding wheel. Interestingly, the grinding wheel incorporates more than 90% of its raw materials as biomass renewable materials; thus, it is generally considered non-toxic. In addition, the future feasibility of this approach to replace some petrochemical resins that are frequently used in the fabrication of grinding wheels is considered.

The predictors of necrotizing enterocolitis in newborns with low birth weight: A retrospective analysis.

ABSTRACT: There are needs to investigate the influencing factors of necrotizing enterocolitis (NEC) in low birth weight (LBW) newborns, to provide insights into the clinical management of NEC.This study was a retrospective cohort study. Infants admitted to our hospital from January 1, 2019 to June 30, 2021 were selected. The clinical characteristics of NEC and no-NEC infants were evaluated. Logistic regression analyses were conducted to assess the risk factors of NEC in LBW infants.A total of 192 LBW infants were included, the incidence of NEC in LBW infants was 35.42%. There were significant differences in the congenital heart disease, sepsis, breastfeeding, blood transfusion and probiotics feeding between NEC and no-NEC group (all P < .05), and there were no significant differences in birth weight, gestational age, mother's pregnancy-induced hypertension, premature rupture of fetal membrane, amniotic fluid pollution, fetal asphyxia, neonatal respiratory distress syndrome and mechanical ventilation between NEC and no-NEC group (all P > .05). Congenital heart disease (OR: 2.128, 95% CI: 1.103-3.511), sepsis (OR: 1.630, 95% CI: 1.022-2.549), and blood transfusion (OR: 1.451, 95% CI: 1.014-2.085) were the independent risk factors for NEC in LBW infants, and breastfeeding (OR: 0.494, 95% CI: 0.023-0.928), probiotics feeding (OR: 0.816, 95% CI: 0.782-0.982) were the protective factors for the NEC in LBW infants. The prognosis of NEC infants undergone surgery treatment was better than that of infants undergone conservative treatments (P = .043).The incidence of NEC in LBW is high, which is affected by many factors, and comprehensive interventions targeted on the risk and protective factors should be made to improve the prognosis of LBW infants.

Gelatinized starch-furanic hybrid as a biodegradable thermosetting resin for fabrication of foams for building materials.

Bio-based biodegradable resin was prepared by condensation of gelatinized starch and furfuryl alcohol, in presence of glyoxal as crosslinker. The resin was blown with different foaming agents and/or flame retardants such as phosphoric or boric acids, to produce environmentally friendly foam structures, given the bio-based nature of the main components, which are both derived from corn. Scanning electron microscopy (SEM) imaging of the samples revealed closed cell structure with a smooth surface. The excellent pulverization ratio and appreciable compression strength compared with the phenol-formaldehyde (PF)-based foam, render them strong candidates for building materials. Different investigations proved characteristics such as low thermal conductivity, good stability against thermal degradation and high limiting oxygen index (LOI) values, support the liability of such structures for application as heat insulating and fire-resistive materials.

A functional loop between YTH domain family protein YTHDF3 mediated m6A modification and phosphofructokinase PFKL in glycolysis of hepatocellular carcinoma.

BACKGROUND & AIMS: N6-methyladenosine (m6A) modification plays a critical role in progression of hepatocellular carcinoma (HCC), and aerobic glycolysis is a hallmark of cancer including HCC. However, the role of YTHDF3, one member of the core readers of the m6A pathway, in aerobic glycolysis and progression of HCC is still unclear. METHODS: Expression levels of YTHDF3 in carcinoma and surrounding tissues of HCC patients were evaluated by immunohistochemistry. Loss and gain-of-function experiments in vitro and in vivo were used to assess the effects of YTHDF3 on HCC cell proliferation, migration and invasion. The role of YTHDF3 in hepatocarcinogenesis was observed in a chemically induced HCC model with Ythdf3-/- mice. Untargeted metabolomics and glucose metabolism phenotype assays were performed to evaluate relationship between YTHDF3 and glucose metabolism. The effect of YTHDF3 on PFKL was assessed by methylated RNA immunoprecipitation assays (MeRIP). Co-immunoprecipitation and immunofluorescence assays were performed to investigate the connection between YTHDF3 and PFKL. RESULTS: We found YTHDF3 expression was greatly upregulated in carcinoma tissues and it was correlated with poor prognosis of HCC patients. Gain-of-function and loss-of-function assays demonstrated YTHDF3 promoted proliferation, migration and invasion of HCC cells in vitro, and YTHDF3 knockdown inhibited xenograft tumor growth and lung metastasis of HCC cells in vivo. YTHDF3 knockout significantly suppressed hepatocarcinogenesis in chemically induced mice model. Mechanistically, YTHDF3 promoted aerobic glycolysis by promoting phosphofructokinase PFKL expression at both mRNA and protein levels. MeRIP assays showed YTHDF3 suppressed PFKL mRNA degradation via m6A modification. Surprisingly, PFKL positively regulated YTHDF3 protein expression, not as a glycolysis rate-limited enzyme, and PFKL knockdown effectively rescued the effects of YTHDF3 overexpression on proliferation, migration and invasion ability of Sk-Hep-1 and HepG2 cells. Notably, co-immunoprecipitation assays demonstrated PFKL interacted with YTHDF3 via EFTUD2, a core subunit of spliceosome involved in pre-mRNA splicing process, and ubiquitination assays showed PFKL could positively regulate YTHDF3 protein expression via inhibiting ubiquitination of YTHDF3 protein by EFTUD2. CONCLUSIONS: our study uncovers the key role of YTHDF3 in HCC, characterizes a positive functional loop between YTHDF3 and phosphofructokinase PFKL in glucose metabolism of HCC, and suggests the connection between pre-mRNA splicing process and m6A modification.

Nanofibers reinforced injectable hydrogel with self-healing, antibacterial, and hemostatic properties for chronic wound healing.

The chronic wounds often hinder wound healing resulting from infection; thus, an ideal wound dressing should be able to maintain a healthy wound microenvironment. Herein, peptide modified nanofibers reinforced hydrogel has been designed by Schiff base dynamic crosslinking. The incorporation of the nanofibers into the hydrogel extremely enhances the stability and mechanical strength of the hydrogel. Taking advantage of the feature, the reinforced hydrogel can restore its original shape while suffering the various external forces on the hydrogel-covered irregular shape wounds. The peptide modified nanofibers reinforced hydrogel (NFRH) not only possesses injectable and self-healing properties, but also inherent antibacterial and hemostatic properties, which can eradicate the bacterial biofilms and induce blood cells and platelets aggregation and finally accelerate the chronic wound healing process. The peptide modified nanofibers reinforced hydrogel has enormous potential to be novel dressing for chronic wounds healing clinically.

A single-cell atlas of liver metastases of colorectal cancer reveals reprogramming of the tumor microenvironment in response to preoperative chemotherapy.

Metastasis is the primary cause of cancer-related mortality in colorectal cancer (CRC) patients. How to improve therapeutic options for patients with metastatic CRC is the core question for CRC treatment. However, the complexity and diversity of stromal context of the tumor microenvironment (TME) in liver metastases of CRC have not been fully understood, and the influence of stromal cells on response to chemotherapy is unclear. Here we performed an in-depth analysis of the transcriptional landscape of primary CRC, matched liver metastases and blood at single-cell resolution, and a systematic examination of transcriptional changes and phenotypic alterations of the TME in response to preoperative chemotherapy (PC). Based on 111,292 single-cell transcriptomes, our study reveals that TME of treatment-naïve tumors is characterized by the higher abundance of less-activated B cells and higher heterogeneity of tumor-associated macrophages (TAMs). By contrast, in tumors treated with PC, we found activation of B cells, lower diversity of TAMs with immature and less activated phenotype, lower abundance of both dysfunctional T cells and ECM-remodeling cancer-associated fibroblasts, and an accumulation of myofibroblasts. Our study provides a foundation for future investigation of the cellular mechanisms underlying liver metastasis of CRC and its response to PC, and opens up new possibilities for the development of therapeutic strategies for CRC.