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To evaluate the vascular impedance of the pulmonary arteries in fetuses with tetralogy of Fallot (TOF) by Doppler echocardiography. A total of 42 fetuses with TOF (TOF group) and 84 gestational age‐matched normal fetuses (control group) were prospectively collected from the Second Xiangya Hospital of Central South University from August 2022 to January 2023. The severity of TOF was classified into mild TOF (zscore ≥−2), moderate TOF (−4 < zscore < −2), or severe TOF (zscore ≤−4) according to the zscore value of the pulmonary annulus diameter. The pulsatility index (PI) of the main pulmonary artery (MPA), distal left pulmonary artery (DLPA), and distal right pulmonary artery (DRPA) were measured by pulsed‐wave Doppler. The differences in clinical data and echocardiographic parameters between TOF group, control group, and TOF subgroups were compared. Compared with the control group, MPA‐PI increased significantly, whereas DLPA‐PI and DRPA‐PI decreased in TOF group (all P< .001). There were no significant differences in MPA‐PI and DRPA‐PI among mild TOF, moderate TOF, and severe TOF (all P> .05). However, DLPA‐PI decreased significantly in severe TOF compared with mild TOF (P< .05). Fetuses with TOF presented increased vascular impedance in the pulmonary trunk and decreased impedance in distal pulmonary artery branches. Further large and follow‐up studies are needed to demonstrate the associations between those changed vascular impedances and the development of PA in patients with TOF.

The polymer materials in nuclear facilities are exposed to high temperatures, radiation, and high loads. Their excellent heat resistance, radiation resistance, and shielding properties are important for the safe operation of nuclear facilities. In this study, 1,2-bis(hydroxymethyl)carborane (CBOH) was first synthesized in large quantities through water extraction and then introduced into an epoxy resin cross-linked network. The incorporation of a carborane structure significantly improved the heat resistance of epoxy. Under air atmosphere, the T5%(the temperature at 5 wt % degradation), T10%(the temperature at 10 wt % degradation), and char yield at 800 °C of the materials were 315.67 °C (16.51 °C increased), 326.29 °C (12.96 °C increased), and 33.22% (33.22% increased), respectively. The maximum decomposition temperature of the material increased from 550 to 750 °C, and 7.05 wt % of the carbon constituent was protected after thermal degradation at 800 °C. The glass transition temperature (Tg) of the materials greatly increased up to over 300 °C after introducing the carborane structure into the networks. The radiation resistance of the material was enhanced due to the in situ capture of oxygen radicals by the carborane structure. Moreover, the incorporation of carborane structure also increased the content of H and B in materials, improving their neutron-shielding capability. This work confers multifunctionality to epoxy resin and enhances its various properties, ensuring the safety of epoxy resin in nuclear facilities.

Polymer-based shielding materials have garnered attention due to their lightweightness, ease of fabrication, and tailorable performance. However, they tend to creep and deform when the materials are exposed to external heat, which may cause a catastrophic disaster due to mechanical failure. In this study, a hybrid loading of graphite (Gt) and boron nitride (BN) fillers was used to improve the thermal dissipation, neutron shielding, and tribological properties of ultrahigh molecular weight polyethylene (UHMWPE), which demonstrate potential applications in nuclear sectors among others. The results revealed that the thermal conductivity of UHMWPE/BN 30 wt %/Gt 40 wt % composite (i.e., BN30Gt40) reached as high as 8.43 W/mK, which was 295% higher than UHMWPE/BN 30 wt %, 201% higher than UHMWPE/Gt 40 wt %, and 1700% higher than pure UHMWPE, respectively. Simulation analysis using Geant4 suggested that UHMWPE/BN/Gt composites exhibited excellent neutron-shielding performance due to the presence of abundant hydrogen and boron elements. In addition, the composites demonstrated excellent friction and wear performance due to the combined effects of constructing transfer film on the surface of the friction pair and timely removal of frictional heat that was generated at the sliding interface.

The aims of this study were to assess the vortex characteristics of left ventricle (LV) in fetuses with coarctation of the aorta (CoA) using high–frame rate ultrasound with blood speckle‐tracking (BST) and explore its relationships with cardiac function and morphology parameters. Thirty fetuses with CoA and 30 gestational‐age matched normal fetuses were included in this cross‐sectional study. The area, length, width, and position of the vortex in the LV were recorded and quantitatively analyzed by BST echocardiography. The associations of vortex properties with ventricular function and morphology were also determined. Based on BST imaging, the LV vortex can be observed in 93% of the fetuses. The fetuses with CoA exhibited significantly larger and wider vortex than the controls (P< .05). Linear regression analysis indicated that vortex area was positively related to sphericity index of LV as well as isovolumic relaxation time (r = .52, P= .003 and r = .42, P= .021). There was a negative correlation between vortex area and mitral valve size (r = −.443, P= .014). No significant association was found between vortex area and myocardial performance index and aortic isthmus size. It is feasible to quantitatively evaluate the left ventricular vortex in fetuses by BST. The fetuses with CoA exhibited greater vortex area and width, and the altered vortex property is associated with geometry of LV. This will facilitate our comprehension of the unique flow patterns and early cardiac remodeling in fetuses with CoA.

Employing in-depth analysis of the combustion characteristics of E-bicycle batteries across different capacities, the NORTHRmethod was proposed, precisely forecasting fire suppression requirements for these battery arrays.

The lethal mutation C423D in Fusarium graminearummyosin I (FgMyoI) occurs close to the binding pocket of the allosteric inhibitor phenamacril and causes severe inhibition on mycelial growth of F. graminearumstrain PH-1. Here, based on extensive Gaussian accelerated molecular dynamics simulations and wet experiments, we elucidate the underlying molecular mechanism of the abnormal functioning of the FgMyoIC423Dmutant at the atomistic level. Our results suggest that the damaging mutation C423D exhibits a synergistic allosteric inhibition mechanism similar to but more robust than that of phenamacril, including effects on the active site and actin binding. Unlike phenamacril-induced closure of Switch2, the mutation results in unfolding of the N-terminal relay helix with a partially opened Switch2 and blocks the structural rearrangement of the relay/SH1 helices, impairing the proper initiation of the recovery stroke. Due to the significant influence of C423D mutation on the function of FgMyoI, designing covalent inhibitors targeting this site holds tremendous potential.

Erectile dysfunction ranks among the prevalent sexual disorders in men. Several studies have indicated a potential link between gut microbiota and erectile dysfunction. To validate this potential association, we were to screen statistical data from genome-wide association studies of gut microbiota and erectile dysfunction. pvalues of less than 1 × 10−5were set as the threshold for screening instrumental variables that were strongly associated with gut microbiota. At the same time, in order to obtain more convincing findings, we further excluded instrumental variables with possible chain imbalance, instrumental variables with the presence of palindromes, instrumental variables with F-statistics less than 10, and instrumental variables associated with risk factors for erectile dysfunction. Five methods including inverse-variance weighted method, weighted median method, weighted mode, Mendelian randomization egger method and Mendelian randomization pleiotropy residual sum and outlier test were then used to analyse the 2591 instrumental variables obtained from the screening. We identified correlations between six gut microbiota and the risk of erectile dysfunction. The genus Ruminococcaceae UCG-013 exhibited an inverse association with the risk of developing erectile dysfunction (0.79 (0.65–0.97), P= 0.0214). Conversely, the genus Tyzzerella3 (1.13 (1.02–1.26), P= 0.0225), genus Erysipelotrichaceae UCG-003 (1.18 (1.01–1.38), P= 0.0412), genus LachnospiraceaeNC2004group (1.19 (1.03–1.37), P= 0.0191), genus Oscillibacter (1.23 (1.08–1.41), P= 0.0022), and family Lachnospiraceae (1.26 (1.05–1.52), P= 0.0123) demonstrated positive associations with an increased risk of erectile dysfunction. These sensitivity analyses of the gut microbiota were consistent. This study demonstrated a possible causal relationship between gut microbiota and erectile dysfunction risk through Mendelian randomization analysis, providing new potential possibilities for the prevention and treatment of erectile dysfunction.

Rabies-virus-based monosynaptic tracing is a widely used technique for mapping neural circuitry, but its cytotoxicity has confined it primarily to anatomical applications. Here we present a second-generation system for labeling direct inputs to targeted neuronal populations with minimal toxicity, using double-deletion-mutant rabies viruses. Viral spread requires expression of both deleted viral genes in transin postsynaptic source cells. Suppressing this expression with doxycycline following an initial period of viral replication reduces toxicity to postsynaptic cells. Longitudinal two-photon imaging in vivo indicated that over 90% of both presynaptic and source cells survived for the full 12-week course of imaging. Ex vivo whole-cell recordings at 5 weeks postinfection showed that the second-generation system perturbs input and source cells much less than the first-generation system. Finally, two-photon calcium imaging of labeled networks of visual cortex neurons showed that their visual response properties appeared normal for 10 weeks, the longest we followed them.

Phosphoinositide-3-kinase-γ (PI3Kγ) is implicated as a target to repolarize tumour-associated macrophages and promote antitumour immune responses in solid cancers1–4. However, cancer cell-intrinsic roles of PI3Kγ are unclear. Here, by integrating unbiased genome-wide CRISPR interference screening with functional analyses across acute leukaemias, we define a selective dependency on the PI3Kγ complex in a high-risk subset that includes myeloid, lymphoid and dendritic lineages. This dependency is characterized by innate inflammatory signalling and activation of phosphoinositide 3-kinase regulatory subunit 5 (PIK3R5), which encodes a regulatory subunit of PI3Kγ5and stabilizes the active enzymatic complex. We identify p21 (RAC1)-activated kinase 1 (PAK1) as a noncanonical substrate of PI3Kγ that mediates this cell-intrinsic dependency and find that dephosphorylation of PAK1 by PI3Kγ inhibition impairs mitochondrial oxidative phosphorylation. Treatment with the selective PI3Kγ inhibitor eganelisib is effective in leukaemias with activated PIK3R5. In addition, the combination of eganelisib and cytarabine prolongs survival over either agent alone, even in patient-derived leukaemia xenografts with low baseline PIK3R5 expression, as residual leukaemia cells after cytarabine treatment have elevated G protein-coupled purinergic receptor activity and PAK1 phosphorylation. Together, our study reveals a targetable dependency on PI3Kγ–PAK1 signalling that is amenable to near-term evaluation in patients with acute leukaemia.

BackgroundThe frequent occurrence of calcification in intracranial artery stenosis increases the risk of ischemic stroke. In previous cases, we have observed a possible relationship between calcification and intracranial in-stent restenosis (ISR) using optical coherence tomography (OCT). Therefore, our study aimed to demonstrate the relationship between intracranial calcification and ISR with a larger sample size.MethodsFor our study patients who underwent OCT for intracranial artery stenosis before stenting were included from May 2020 to October 2022. Follow-up assessments were performed using transcranial color-coded duplex (TCCD) sonography ultrasonography to detect cases of ISR.ResultsWe recruited 54 patients, 15 of them were excluded as they did not meet the study criteria. Our study included 39 patients, of whom 21 had calcification, and 18 did not. The results of our study revealed a significant association between calcification and intracranial ISR (9 (42.86) vs 2 (11.11), p=0.0375). Notably, patients with macrocalcification were more likely to undergo ISR than patients with spotty calcification (77.78% vs 22.22%, p=0.03).ConclusionOCT imaging demonstrates that calcification is an essential risk factor for intracranial ISR. These findings have important implications for individualized treatment. They provide valuable insights for optimizing stent design and exploring potential mechanisms of intracranial ISR.Trial registration numberClinicalTrials.gov Identifier: NCT05550077.

PI3K-δ inhibitors have shown impressive activity in lymphoid malignancies but have been hampered by autoimmune and infectious toxicities, leading to market withdrawals. We previously demonstrated activity of the PI3K-δγ inhibitor duvelisib in T cell lymphomas (TCLs) that was associated with inflammatory adverse events. As reported here, we conducted a phase 1b/2a study of duvelisib in combination with either romidepsin (n= 66) or bortezomib (n= 32) in patients with relapsed/refractory TCL and found that the addition of romidepsin, but not bortezomib, appeared to increase efficacy while attenuating PI3K inhibitor-driven toxicity. The primary endpoint of the study was to determine the safety and maximum tolerated dose of duvelisib, which was 75 mg twice daily when combined with romidepsin versus 25 mg twice daily when combined with bortezomib. The most common adverse events were neutropenia (42%, 25/59) and fatigue (37%, 22/59) in patients treated with duvelisib and romidepsin and diarrhea (48%, 11/23) and neutropenia (30%, 7/23) in patients treated with duvelisib and bortezomib. Duvelisib and romidepsin resulted in less grade 3/4 hepatotoxicity (14%, 8/59) compared to 40% (14/35) in our previous study with duvelisib monotherapy. This was associated with reductions in circulating inflammatory mediators and myeloid cell inflammatory gene expression. Secondary endpoints of overall and complete response rates were 55% (35/64) and 34% (22/64) for patients treated with duvelisib and romidepsin and 34% (11/32) and 13% (4/32) for patients treated with duvelisib and bortezomib. Among patients with peripheral T cell lymphomas (PTCLs), overall and complete response rates of duvelisib and romidepsin were 56% (27/48) and 44% (21/48), respectively, with exploratory analyses showing increased response rates in patients with a follicular helper T cell subtype. These findings support further development of combined PI3K and histone deacetylase (HDAC) inhibition in TCLs and suggest a unique strategy to enable PI3K inhibitor-based combinations for additional patient populations. ClinicalTrials.gov identifier: NCT02783625.

Erectile dysfunction is a common sexual disorder in men. Some studies have found a strong association between some serum metabolites and erectile dysfunction. To investigate this association further, we used bidirectional Mendelian randomisation to investigate causality and possible biological mechanisms.Firstly, this study screened the statistics of genome-wide association studies of serum metabolites and erectile dysfunction to obtain instrumental variables. Inverse variance weighting was used as the primary method for causal effect analysis of instrumental variables in forward or reverse Mendelian randomisation, and the results obtained by MR-Egger regression and the weighted median method were used as references. Subsequently, the metabolites causally associated with erectile dysfunction were subjected to replication analyses and meta-analyses, and the results of the meta-analyses were analysed by pathway analyses to find influential pathways. In this process, Mendelian randomisation results need to be assessed for stability and reliability using sensitivity analysis.It was found that a total of six serum metabolites were causally associated with erectile dysfunction in a forward Mendelian randomisation study. 1,3,7-trimethyluraten (0.85 (0.73–0.99), P= 0.0368), ergothioneine (0.65 (0.45–0.94), P= 0.0226) and gamma-glutamylglutamate (0.63 (0.46–0.88), P= 0.0059) were protective against the development of erectile dysfunction, whereas 2-hydroxyhippurate (1.10 (1.02–1.19), P= 0.0152), N2,N2-dimethylguanosine (1.57 (1.02–2.40), P= 0.0395) and octanoylcarnitine (1.38 (1.06–1.82), P= 0.0183) were able to induce the development of erectile dysfunction. In addition, metabolic pathway analysis showed that 1,3,7-trimethylurate was able to influence the development of erectile dysfunction via the caffeine metabolism pathway (P= 0.0454). On the other hand, reverse Mendelian randomisation analysis showed that erectile dysfunction reduced serum homocitrulline levels (0.99 (0.97–1.00), P= 0.0360). Sensitivity analyses, including heterogeneity tests and pleiotropy tests, confirmed the reliability of the results.In conclusion, this study demonstrated a bidirectional causal relationship between serum metabolites and erectile dysfunction using bidirectional Mendelian randomisation analysis and replication meta-analysis. On this basis, this study provides a new direction of thinking and strong evidence for the therapeutic application and adjunctive diagnosis of serum metabolites in erectile dysfunction, and provides a certain reference value for subsequent related studies.

Hybrid rice has achieved high grain yield and greatly contributes to food security, but the manual-labour-intensive hybrid seed production process limits fully mechanized hybrid rice breeding. For next-generation hybrid seed production, the use of small-grain male sterile lines to mechanically separate small hybrid seeds from mixed harvest is promising. However, it is difficult to find ideal grain-size genes for breeding ideal small-grain male sterile lines without penalties in the number of hybrid seeds and hybrid rice yield. Here we report that the use of small-grain alleles of the ideal grain-size gene GSE3in male sterile lines enables fully mechanized hybrid seed production and dramatically increases hybrid seed number in three-line and two-line hybrid rice systems. The GSE3gene encodes a histone acetyltransferase that binds histones and influences histone acetylation levels. GSE3 is recruited by the transcription factor GS2 to the promoters of their co-regulated grain-size genes and influences the histone acetylation status of their co-regulated genes. Field trials demonstrate that genome editing of GSE3can be used to immediately improve current elite male sterile lines of hybrid rice for fully mechanized hybrid rice breeding, providing a new perspective for mechanized hybrid breeding in other crops.

This paper adopts the DID approach to investigate the trade destruction effects and trade deflection effects of the US additional tariffs. The authors find that the US additional tariffs significantly reduce China’s exports of tariffed products to the US (i.e., trade destruction effect), especially intermediate and labor-intensive products. On the other hand, they significantly increase China’s exports of tariffed products to the third market (i.e., trade deflection effect). For the $50 billion list, both the trade destruction effect and trade deflection effect are concentrated on processing exports, and the US additional tariffs significantly increase China’s exports of tariffed products to ASEAN, Japan and Australia. For the $200 billion list, the US additional tariffs boost China’s exports of chemicals, textiles, wood, metal products, furniture and other products to the EU, Australia, Japan, South Africa and Hong Kong, China. Furthermore, most trade deflections are not realized by lowering export prices, indicating that the trade deflections could compensate for the profit losses caused by the US additional tariffs to a certain extent. The proposed results suggest that searching for substitutions of export markets and a more open trade policy is an important way to avoid profit losses and reduce risks for enterprises and economies suffering from trade frictions.

In the first two years of the COVID-19 pandemic, per capita mortality varied by more than a hundredfold across countries, despite most implementing similar nonpharmaceutical interventions. Factors such as policy stringency, gross domestic product, and age distribution explain only a small fraction of mortality variation. To address this puzzle, we built on a previously validated pandemic model in which perceived risk altered societal responses affecting SARS-CoV-2 transmission. Using data from more than 100 countries, we found that a key factor explaining heterogeneous death rates was not the policy responses themselves but rather variation in responsiveness. Responsiveness measures how sensitive communities are to evolving mortality risks and how readily they adopt nonpharmaceutical interventions in response, to curb transmission. We further found that responsiveness correlated with two cultural constructs across countries: uncertainty avoidance and power distance. Our findings show that more responsive adoption of similar policies saves many lives, with important implications for the design and implementation of responses to future outbreaks.

Current therapy for acute myeloid leukemia (AML) is largely hindered by the development of drug resistance of commonly used chemotherapy drugs, including cytarabine, daunorubicin, and idarubicin. In this study, we investigated the molecular mechanisms underlying the chemotherapy drug resistance and potential strategy to improve the efficacy of these drugs against AML. By analyzing data from ex vivo drug-response and multi-omics profiling public data for AML, we identified autophagy activation as a potential target in chemotherapy-resistant patients. In THP-1 and MV-4-11 cell lines, knockdown of autophagy-regulated genes ATG5or MAP1LC3Bsignificantly enhanced AML cell sensitivity to the chemotherapy drugs cytarabine, daunorubicin, and idarubicin. In silico screening, we found that chloroquine phosphate mimicked autophagy inactivation. We showed that chloroquine phosphate dose-dependently down-regulated the autophagy pathway in MV-4-11 cells. Furthermore, chloroquine phosphate exerted a synergistic antitumor effect with the chemotherapy drugs in vitro and in vivo. These results highlight autophagy activation as a drug resistance mechanism and the combination therapy of chloroquine phosphate and chemotherapy drugs can enhance anti-AML efficacy.

The effects of different annealing processes on the phase precipitation behavior and corrosion properties of copper-bearing 430 ferritic stainless steel were systematically investigated. The shape, quantity and distribution of copper-rich precipitates by different annealing processes were characterized by scanning electron microscopy, transmission electron microscopy, backscatter electron and backscatter diffraction. The pitting resistance behavior in simulated physiological saline environments (0.9 wt.% NaCl) was investigated using electrochemical workstation and X-ray photoelectron spectroscopy. The results showed that the copper-rich phase prepared by repeated rolling and annealing gradually changed from long needle-like to short thick rod-like and granular, whose distribution tended to be uniform and diffusive, and the number of copper-rich phases increased. After solution/antibacterial annealing process, the size and density of the copper-rich phase increase, resulting in a discontinuity of the passivation film on the stainless steel, which reduces the pitting resistance to some extent. The refinement mechanism revealed that pre-deformation brings about a modification in both precipitation mechanism and growth kinetics of epsilon copper.

Prostate cancer (PCa) is a malignant tumor of the urinary system. CircABCC4 has been demonstrated to promote the development of PCa; however, its regulatory mechanisms in PCa progression remain largely unknown. We found that circABCC4 was highly expressed in PCa tissues and cells, and elevated circABCC4 level indicated a poor overall survival of PCa patients. METTL3 overexpression increased circABCC4 expression via m6A modification in PCa cells. Functionally, knockdown of circABCC4 or METTL3 repressed PCa cell stemness, migration, and invasion in vitro and delayed PCa cancer growth and metastasis in vivo. circABCC4 knockdown-mediated inhibition in PCa cell stemness and metastasis could be counteracted by overexpression of wild-type circABCC4 with m6A sites. Mechanistically, circABCC4 recruited IGF2BP2 protein to CCAR1 mRNA, thereby enhancing CCAR1 mRNA stability and subsequent activation of the Wnt/β-catenin pathway. Overexpression of CCAR1 counteracted the inhibitory effect of circABCC4 silencing on PCa cell stemness and metastasis. These results revealed that m6A-modified circABCC4 by METTL3 facilitated PCa cell stemness and metastasis by interacting with IGF2BP2 to increase the stability and expression of CCAR and subsequent expression of Wnt/β-catenin target genes. Our findings suggest circABCC4 as a promising therapeutic target for PCa.

Although immune checkpoint inhibition has been shown to effectively activate antitumor immunity in various tumor types, only a small subset of patients can benefit from PD-1/PD-L1 blockade. CD47 expressed on tumor cells protects them from phagocytosis through interaction with SIRPα on macrophages, while PD-L1 dampens T cell-mediated tumor killing. Therefore, dual targeting PD-L1 and CD47 may improve the efficacy of cancer immunotherapy. A chimeric peptide Pal-DMPOP was designed by conjugating the double mutation of CD47/SIRPα blocking peptide (DMP) with the truncation of PD-1/PD-L1 blocking peptide OPBP-1(8–12) and was modified by a palmitic acid tail. Pal-DMPOP can significantly enhance macrophage-mediated phagocytosis of tumor cells and activate primary T cells to secret IFN-γ in vitro. Due to its superior hydrolysis-resistant activity as well as tumor tissue and lymph node targeting properties, Pal-DMPOP elicited stronger anti-tumor potency than Pal-DMP or OPBP-1(8–12) in immune-competent MC38 tumor-bearing mice. The in vivoanti-tumor activity was further validated in the colorectal CT26 tumor model. Furthermore, Pal-DMPOP mobilized macrophage and T-cell anti-tumor responses with minimal toxicity. Overall, the first bispecific CD47/SIRPα and PD-1/PD-L1 dual-blockade chimeric peptide was designed and exhibited synergistic anti-tumor efficacy via CD8+T cell activation and macrophage-mediated immune response. The strategy could pave the way for designing effective therapeutic agents for cancer immunotherapy.

Diabetic wound healing has become a serious healthcare challenge. The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction, resulting in chronic inflammation, abnormal vascular function, and tissue necrosis. To solve these issues, we developed a double-network hydrogel, constructed with pluronic F127 diacrylate (F127DA) and hyaluronic acid methacrylate (HAMA), and enhanced by SS31-loaded mesoporous polydopamine nanoparticles (MPDA NPs). As components, SS31, a mitochondria-targeted peptide, maintains mitochondrial function, reduces mitochondrial reactive oxygen species (ROS) and thus regulates macrophage polarization, as well as promoting cell proliferation and migration, while MPDA NPs not only scavenge ROS and exert an anti-bacterial effect by photothermal treatment under near-infrared light irradiation, but also control release of SS31 in response to ROS. This F127DA/HAMA–MPDA@SS31 (FH–M@S) hydrogel has characteristics of adhesion, superior biocompatibility and mechanical properties which can adapt to irregular wounds at different body sites and provide sustained release of MPDA@SS31 (M@S) NPs. In addition, in a diabetic rat full thickness skin defect model, the FH–M@S hydrogel promoted macrophage M2 polarization, collagen deposition, neovascularization and wound healing. Therefore, the FH–M@S hydrogel exhibits promising therapeutic potential for skin regeneration.

The integration of wireless-powered communication and backscatter communication (BackCom) is envisioned as a promising communication paradigm for the future Internet of Things (IoT), where resource allocation (RA) as a critical technique can improve achievable capacity by dynamically adjusting system parameters (e.g., transmit power, beamforming vectors). However, the existing RA algorithms consider the ideal cases of perfect channel state information and linear energy harvesting (EH), which will deteriorate system performance. To fill this gap, in this paper, we investigate a robust RA problem for a wireless-powered BackCom system with non-orthogonal multiple access (NOMA) under the consideration of practical channel uncertainties and nonlinear EH models. The robust RA problem with Euclidean spherical uncertainties is formulated by optimizing the transmit beamforming vector of the access point (AP), the transmit power of each IoT device, and time allocation factors, where the maximum power constraint of the AP, the time frame constraint, the minimum EH constraint, and the quality of service constraint of each user are considered simultaneously. Subsequently, according to the block coordinate descent iterative method, an iteration-based robust RA algorithm is proposed by using the successive convex approximation, S-procedure, semidefinite relaxation, and Gaussian randomization methods. Simulation results prove that our proposed algorithm can drastically enhance system robustness compared to the non-robust algorithm and several benchmark algorithms.

The development of protective fabrics that are capable of capturing and detoxifying a wide range of lethal chemical warfare agents (CWAs) in an efficient way is of great importance for individual protection gears/clothing. In this work, unique metal–organic framework (MOF)-on-MOF nanofabrics were fabricated through facile self-assembly of UiO-66-NH2and MIL-101(Cr) crystals on electrospun polyacrylonitrile (PAN) nanofabrics and exhibited intriguing synergistic effects between the MOF composites on the detoxification of both nerve agent and blistering agent simulants. MIL-101(Cr), although not catalytic, facilitates the enrichment of CWA simulants from solution or air, thereby delivering a high concentration of reactants to catalytic UiO-66-NH2coated on its surface and providing an enlarged contact area for CWA simulants with the Zr6nodes and aminocarboxylate linkers compared to solid substrates. Consequently, the as-prepared MOF-on-MOF nanofabrics showed a fast hydrolysis rate (t1/2= 2.8 min) for dimethyl 4-nitrophenylphosphate (DMNP) in alkaline solutions and a high removal rate (90% within 4 h) of 2-(ethylthio)-chloroethane (CEES) under environmental conditions, considerably surpassing their single-MOF counterparts and the mixture of two MOF nanofabrics. This work demonstrates synergistic detoxification of CWA simulants using MOF-on-MOF composites for the first time and has the potential to be extended to other MOF/MOF pairs, which provides new ideas for the development of highly efficient toxic gas-protective materials.

Glioblastoma (GBM) is the most lethal primary brain tumor in adults and harbors a subpopulation of glioma stem cells (GSCs). Enhancer of Zeste Homolog 2 (EZH2), a histone lysine methyltransferase, deeply involves in the stemness maintenance of GSC. However, the precise mechanism and therapeutic potential remain elusive. We postulated that the interactome of EZH2 in GSC is unique. Therefore, we performed proteomic and transcriptomic research to unveil the oncogenic mechanism of EZH2. Immunoprecipitation and mass spectrometry were used to identify proteins that co-precipitate with EZH2. We show that EZH2 binds to heterochromatin protein 1 binding protein 3 (HP1BP3) in GSCs and impairs the methylation of H3K9. Overexpression of HP1BP3 enhances the proliferation, self-renewal and temozolomide (TMZ) resistance of GBM cells. Furthermore, EZH2 and HP1BP3 co-activate WNT7Bexpression thereby increasing TMZ resistance and stemness of GBM cells. Importantly, inhibition of WNT7B autocrine via LGK974 effectively reverses the TMZ resistance. Our work clarifies a new oncogenic mechanism of EZH2 by which it interacts with HP1BP3 and epigenetically activates WNT7Bthereby promoting TMZ resistance in GSCs. Our results provide a rationale for targeting WNT/β-catenin pathway as a promising strategy to overcome TMZ resistance in GSCs.

The development of functional materials that can detoxify multiple chemical warfare agents (CWAs) at the same time is of great significance to cope with the uncertainty of CWA use in real-world situations. Although many catalysts capable of detoxifying CWAs have been reported, there is still a lack of effective means to integrate these catalytic-active materials on practical fibers/fabrics to achieve effective protection against coexistence of a variety of CWAs. In this work, by a combination of electrospinning and in situ solvothermal reaction, PAN@Zr(OH)4@MOF-808 nanofiber membranes were prepared for detoxification of both nerve agent and blistering agent simulants dimethyl 4-nitrophenyl phosphate (DMNP) and 2-chloroethyl ethyl sulfide (CEES). Under the catalytic effect of the MOF-808 component, DMNP hydrolysis with a half-life as short as 1.19 min was achieved. Meanwhile, an 89.3% CEES removal rate was obtained within 12 h by adsorption and catalysis of MOF-808 and Zr(OH)4components at ambient conditions, respectively. PAN@Zr(OH)4@MOF-808 nanofiber membranes also showed a superior blocking effect on CEES compared to bare PAN and PAN@Zr(OH)4nanofiber membranes. Simultaneous protection against DMNP and CEES showed effective inhibition of both simulants for at least 2 h. The preparation method also imparted intrinsically good interfacial adhesion between the components, contributing to the excellent recycling stability of PAN@Zr(OH)4@MOF-808 nanofiber membranes. Therefore, the prepared composite nanofabrics have great application potential, which provides a new idea for the construction of broad-spectrum protective detoxification materials.

Previous studies have demonstrated that circST6GALNAC6 is a tumor suppressor in bladder cancer. However, the role of circST6GALNAC6 in ferroptosis remains unclear. In the current study, ferroptosis was induced in bladder cancer cells by erastin. Functional experiments showed that overexpression of circST6GALNAC6 promoted ferroptosis of bladder cancer cells in vitro and in vivo. Mechanistic studies revealed that circST6GALNAC6 bound to the N-terminus of small heat shock protein 1 (HSPB1) and thus blocked the erastin-induced phosphorylation of HSPB1 at the Ser-15 site, a phosphorylation site in the protective response to ferroptosis stress. In addition, protein kinase C inhibited circST6GALNAC6-induced ferroptosis by increasing the overall phosphorylation level of HSPB1, further demonstrating the role of phosphorylation activation of HSPB1 in resistance to ferroptosis. Finally, the involvement of the HSPB1/p38 MAPK pathway in the downstream signal transduction of circST6GALNAC6 in bladder cancer ferroptosis regulation was determined. The regulatory mechanism of ferroptosis sensitivity dependent on circST6GALNAC6 expression levels in bladder cancer was revealed as circRNA regulation of various protein functions. CircST6GALNAC6 inhibits HSPB1 and promotes cell ferroptosis by occupying the phosphorylation site (Ser-15) of HSBP1 and activating the P38 MAPK signaling pathway. Therefore, enhancing the expression of circST6GALNAC6 to promote ferroptosis or using circST6GALNAC6 as a biomarker of ferroptosis sensitivity is of considerable importance to the development and application of ferroptosis intervention methods in bladder cancer.