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Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.

Metal–semiconductor junctions play an important role in the development of electronic and optoelectronic devices. A Schottky junction photodetector based on two-dimensional (2D) materials is promising for self-powered photodetection with fast response speed and large signal-to-noise ratio. However, it usually suffers from an uncontrolled Schottky barrier due to the Fermi level pinning effect arising from the interface states. In this work, all-2D Schottky junctions with near-ideal Fermi level depinning are realized, attributed to the high-quality interface between 2D semimetals and semiconductors. We further demonstrate asymmetric diodes based on multilayer graphene/MoS2/PtSe2with a current rectification ratio exceeding 105and an ideality factor of 1.2. Scanning photocurrent mapping shows that the photocurrent generation mechanism in the heterostructure switches from photovoltaic effect to photogating effect at varying drain biases, indicating both energy conversion and optical sensing are realized in a single device. In the photovoltaic mode, the photodetector is self-powered with a response time smaller than 100 μs under the illumination of a 405 nm laser. In the photogating mode, the photodetector exhibits a high responsivity up to 460 A/W originating from a high photogain. Finally, the photodetector is employed for single-pixel imaging, demonstrating its high-contrast photodetection ability. This work provides insight into the development of high-performance self-powered photodetectors based on 2D Schottky junctions.

Pharmacosiderite Mo4P3O16(Pharma-MoPO) consists of [Mo4O4] cubane unit and [PO4] tetrahedral to form an open framework with a microporous structure similar to that of LTA-type zeolite. Although attractive applications are expected due to its microporous structure and redox-active components, its physicochemical properties have been poorly investigated due to the specificity of its synthesis, which requires a high hydrothermal synthesis temperature of 360 °C. In this study, we succeeded in synthesizing Pharma-MoPO by hydrothermal synthesis at 230 °C, which can be applied using a commercially available autoclave by changing the metal source. Through the study of the solids and liquids obtained after hydrothermal syntheses, the formation process of Pharma-MoPO under our studied synthesis conditions was proposed. Advanced characterizations provided detailed structural information on Pharma-MoPO, including the location site of a countercation NH4+. Pharma-MoPO could adsorb CO2with the amount close to the number of cages without removing NH4+. Pharma-MoPO exhibited stable catalytic activity for the hydrodesulfurization of thiophene while maintaining its crystal structure, except for the introduction of sulfide by replacing lattice oxygens. Pharmacosiderite Mo4P3O16was successfully obtained by hydrothermal synthesis at a moderate temperature, and its microporosity for CO2adsorption and catalytic properties for hydrodesulfurization were discovered.

Lignocellulose has the potential to become a bio-based adsorbent due to its biodegradability and renewability. In this study, a novel polydopamine-functionalized-lignin (lignin@PDA), prepared via self-polymerization of dopamine (PDA) on lignin, was used as a bio-based adsorbent for rapid scavenging of hexavalent chromium (Cr(VI)). The morphology, functional groups, crystalline structure, and chemical composition of lignin@PDA were characterized with a scanning electron microscope–energy dispersive spectrometer, Fourier transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The Cr(VI) adsorption process of lignin@PDA was studied using batch experiments as a function of pH, ionic strength, adsorbent dose, and contact time at room temperature. The adsorption rate of lignin@PDA was five times greater than that of the unmodified lignin, with a maximum adsorption capacity of 102.6 mg/g in an acidic medium. The adsorption of Cr(VI) on lignin@PDA fit the pseudo-second-order equation and the Freundlich model, indicating that the adsorption process was mainly dominated by chemisorption and surface complexation. The thermodynamic parameters showed that adsorption of Cr(VI) on lignin@PDA was an endothermic and spontaneous process. The X-ray absorption fine structure results showed that sorption and reduction of Cr(VI) into Cr(III) occurred simultaneously on lignin. Moreover, PDA coating not only improved the reactivity of lignin but also promoted the complete reduction of Cr(VI) by lignin. According to these results, polydopamine-functionalized-lignin is a promising bio-based adsorbent for immobilization of Cr(VI) from wastewater.

ObjectiveDuring the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with future research.DesignWe conducted a systematic review of the literature for guidelines and consensus statements published between January 2010 and February 2023 that address the diagnosis and management of GIM.ResultsFrom 426 manuscripts identified, 16 guidelines were assessed. There was consistency across guidelines regarding the purpose of endoscopic surveillance of GIM, which is to identify prevalent neoplastic lesions and stage gastric preneoplastic conditions. The guidelines also agreed that only patients with high-risk GIM phenotypes (eg, corpus-extended GIM, OLGIM stages III/IV, incomplete GIM subtype), persistent refractory Helicobacter pyloriinfection or first-degree family history of gastric cancer should undergo regular-interval endoscopic surveillance. In contrast, low-risk phenotypes, which comprise most patients with GIM, do not require surveillance. Not all guidelines are aligned on histological staging systems. If surveillance is indicated, most guidelines recommend a 3-year interval, but there is some variability. All guidelines recommend H. pylorieradication as the only non-endoscopic intervention for gastric cancer prevention, while some offer additional recommendations regarding lifestyle modifications. While most guidelines allude to the importance of high-quality endoscopy for endoscopic surveillance, few detail important metrics apart from stating that a systematic gastric biopsy protocol should be followed. Notably, most guidelines comment on the role of endoscopy for gastric cancer screening and detection of gastric precancerous conditions, but with high heterogeneity, limited guidance regarding implementation, and lack of robust evidence.ConclusionDespite heterogeneous populations and practices, international guidelines are generally aligned on the importance of GIM as a precancerous condition and the need for a risk-stratified approach to endoscopic surveillance, as well as H. pylorieradication when present. There is room for harmonisation of guidelines regarding (1) which populations merit index endoscopic screening for gastric cancer and GIM detection/staging; (2) objective metrics for high-quality endoscopy; (3) consensus on the need for histological staging and (4) non-endoscopic interventions for gastric cancer prevention apart from H. pylorieradication alone. Robust studies, ideally in the form of randomised trials, are needed to bridge the ample evidence gaps that exist.

Gut microbiota have been reported to play an important role in the occurrence and development of malignant tumors. Currently, clinical studies have identified specific gut microbiota and its metabolites associated with efficacy of immunotherapy in multiple types of cancers. Preclinical investigations have elucidated that gut microbiota modulate the antitumor immunity and affect the efficacy of cancer immunotherapy. Certain microbiota and its metabolites may favorably remodel the tumor microenvironment by engaging innate and/or adaptive immune cells. Understanding how the gut microbiome interacts with cancer immunotherapy opens new avenues for improving treatment strategies. Fecal microbial transplants, probiotics, dietary interventions, and other strategies targeting the microbiota have shown promise in preclinical studies to enhance the immunotherapy. Ongoing clinical trials are evaluating these approaches. This review presents the recent advancements in understanding the dynamic interplay among the host immunity, the microbiome, and cancer immunotherapy, as well as strategies for modulating the microbiome, with a view to translating into clinical applications.

Background and aimsDeregulation of RNA N6-methyladenosine (m6A) modification in intestinal epithelial cells (IECs) influences intestinal immune cells and leads to intestinal inflammation. We studied the function of fat mass-and obesity-associated protein (FTO), one of the m6A demethylases, in patients with ulcerative colitis (UC).MethodsWe analysed colon tissues of Ftoflox/flox; Villin-cre mice and their Ftoflox/floxlittermates with dextran sulfate sodium (DSS) using real-time PCR and 16s rRNA sequencing. RNA and methylated RNA immunoprecipitation sequencing were used to analyse immunocytes and IECs. Macrophages were treated with conditioned medium of FTO-knockdown MODE-K cells or sphingosine-1-phosphate (S1P) and analysed for gene expression. Liquid chromatograph mass spectrometry identified C16-ceramide.ResultsFTO downregulation was identified in our in-house cohort and external cohorts of UC patients. Dysbiosis of gut microbiota, increased infiltration of proinflammatory macrophages, and enhanced differentiation of Th17 cells were observed in Ftoflox/flox;Villin-cre mice under DSS treatment. FTO deficiency resulted in an increase in m6A modification and a decrease in mRNA stability of CerS6, the gene encoding ceramide synthetase, leading to the downregulation of CerS6 and the accumulation of S1P in IECs. Subsequentially, the secretion of S1P by IECs triggered proinflammatory macrophages to secrete serum amyloid A protein 1/3, ultimately inducing Th17 cell differentiation. In addition, through bioinformatic analysis and experimental validation, we identified UC patients with lower FTO expression might respond better to vedolizumab treatment.ConclusionsFTO downregulation promoted UC by decreasing CerS6 expression, leading to increased S1P accumulation in IECs and aggravating colitis via m6A-dependent mechanisms. Lower FTO expression in UC patients may enhance their response to vedolizumab treatment.

Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer’s disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aβ and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD.

Gemcitabine resistance is a major obstacle to the effectiveness of chemotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, new strategies are needed to sensitize cancer cells to gemcitabine. Here, we constructed gemcitabine-resistant PDAC cells and analyzed them with RNA-sequence. Employing an integrated approach involving bioinformatic analyses from multiple databases, TGFB2 is identified as a crucial gene in gemcitabine-resistant PDAC and is significantly associated with poor gemcitabine therapeutic response. The patient-derived xenograft (PDX) model further substantiates the gradual upregulation of TGFB2 expression during gemcitabine-induced resistance. Silencing TGFB2 expression can enhance the chemosensitivity of gemcitabine against PDAC. Mechanistically, TGFB2, post-transcriptionally stabilized by METTL14-mediated m6A modification, can promote lipid accumulation and the enhanced triglyceride accumulation drives gemcitabine resistance by lipidomic profiling. TGFB2 upregulates the lipogenesis regulator sterol regulatory element binding factor 1 (SREBF1) and its downstream lipogenic enzymes via PI3K-AKT signaling. Moreover, SREBF1 is responsible for TGFB2-mediated lipogenesis to promote gemcitabine resistance in PDAC. Importantly, TGFB2 inhibitor imperatorin combined with gemcitabine shows synergistic effects in gemcitabine-resistant PDAC PDX model. This study sheds new light on an avenue to mitigate PDAC gemcitabine resistance by targeting TGFB2 and lipid metabolism and develops the potential of imperatorin as a promising chemosensitizer in clinical translation.

Survivin, a homodimeric protein and a member of the IAP family, plays a vital function in cell survival and cycle progression by interacting with various proteins and complexes. Its expression is upregulated in cancers but not detectable in normal tissues. Thus, it has been regarded and validated as an ideal cancer target. However, survivin is “undruggable” due to its lack of enzymatic activities or active sites for small molecules to bind/inhibit. Academic and industrial laboratories have explored different strategies to overcome this hurdle over the past two decades, with some compounds advanced into clinical testing. These strategies include inhibiting survivin expression, its interaction with binding partners and homodimerization. Here, we provide comprehensive analyses of these strategies and perspective on different small molecule survivin inhibitors to help drug discovery targeting “undruggable” proteins in general and survivin specifically with a true survivin inhibitor that will prevail in the foreseeable future.

Recent studies revealed that intestinal microbiota played important roles in colorectal cancer (CRC) carcinogenesis. Particularly, Fusobacterium nucleatumwas confirmed to promote the proliferation and metastasis of CRC. Therefore, targeting F. nucleatummay be a potential preventive and therapeutic approach for CRC. Herein, 2,272 off-patent drugs were screened inhibitory activity against F. nucleatum. Among the hits, nitisinone was identified as a promising anti-F. nucleatumlead compound. Further optimization of nitisinone led to the discovery of more potent derivatives. Particularly, compounds 19qand 22cshowed potent anti-F. nucleatumactivity (MIC50= 1 and 2 μg/mL, respectively) with low cytotoxicity. Among them, compound 19qeffectively attenuated the migratory ability of MC-38 cells induced by F. nucleatum. Preliminary mechanism studies suggested that nitisinone and its derivatives might act by downregulating nitroreductase and tryptophanase. Thus, the development of small molecule F. nucleatuminhibitors represents an effective strategy to treat CRC.

Functionalized crystalline solids based on metal–organic frameworks (MOFs) enable efficient luminescence detection and high proton conductivity, making them crucial in the realms of environmental monitoring and clean energy. Here, two structurally and functionally distinct zinc-based MOFs, [Zn(TTDPa)(bodca)]·H2O (1) and [Zn(TTDPb)(bodca)]·H2O (2), were successfully designed and synthesized using 3,6-di(pyridin-4-yl)thieno[3,2-b]thiophene (TTDPa) and 2,5-di(pyridin-4-yl)thieno[3,2-b]thiophene (TTDPb) as ligands, in the presence of bicyclo[2.2.2]octane-1,4-dicarboxylic acid (H2bodca). Both 1and 2display a three-dimensional (3D) structure with 5-fold interpenetration, and notably, 2forms a larger one-dimensional pore measuring 17.16 × 10.81 Å2in size. Fluorescence experiments demonstrate that 1and 2can function as luminescent sensors for nitrofurantoin (NFT) and nitrofurazone (NFZ) with low detection limits, remarkable selectivity, and good recyclability. A comprehensive analysis was conducted to investigate the differing sensing effects of compounds 1and 2and to explore potential sensing mechanisms. Additionally, at 328 K and 98% relative humidity, 1and 2exhibit proton conductivity values of 2.13 × 10–3and 4.91 × 10–3S cm–1, respectively, making them suitable proton-conducting materials. Hence, the integration of luminescent sensing and proton conductivity in monophasic 3D Zn-MOFs holds significant potential for application in intelligent multitasking devices.

Skeletal muscle mass and quality assessed by computed tomography (CT) images of the third lumbar vertebra (L3) level have been established as risk factors for poor clinical outcomes in several illnesses, but the relevance for dialysis patients is unclear. A few studies have suggested a correlation between CT‐determined skeletal muscle mass and quality at the first lumbar vertebra (L1) level and adverse outcomes. Generally, chest CT does not reach beyond L1. We aimed to determine whether opportunistic CT scan (chest CT)‐determined skeletal muscle mass and quality at L1 are associated with mortality in initial‐dialysis patients. This 3‐year multicentric retrospective study included initial‐dialysis patients from four centres between 2014 and 2017 in China. Unenhanced CT images of the L1 and L3 levels were obtained to assess skeletal muscle mass [by skeletal muscle index, (SMI), cm2/m2] and quality [by skeletal muscle density (SMD), HU]. Skeletal muscle measures at L1 were compared with those at L3. The sex‐specific optimal cutoff values of L1 SMI and L1 SMD were determined in relation to all‐cause mortality. The outcomes were all‐cause death and cardiac death. Cox regression models were applied to investigate the risk factors for death. A total of 485 patients were enrolled, of whom 257 had both L1 and L3 images. Pearson's correlation coefficient between L1 and L3 SMI was 0.84 (P< 0.001), and that between L1 and L3 SMD was 0.90 (P< 0.001). No significant association between L1 SMI and mortality was observed (P> 0.05). Low L1 SMD (n= 280, 57.73%) was diagnosed based on the optimal cutoff value (<39.56 HU for males and <33.06 HU for females). Multivariate regression analysis revealed that the low L1 SMD group had higher risks of all‐cause death (hazard ratio 1.80; 95% confidence interval 1.05–3.11, P= 0.034) and cardiac death (hazard ratio 3.74; 95% confidence interval 1.43–9.79, P= 0.007). In initial‐dialysis patients, there is high agreement between the L1 and L3 measures for SMI and SMD. Low SMD measured at L1, but not low SMI, is an independent predictor of both all‐cause death and cardiac death.

This study reports a comprehensive investigation into the active sites and reaction mechanism for the selective catalytic reduction of NO by NH3(NH3-SCR) over phosphate-loaded ceria (P/CeO2). Catalyst characterization and density functional theory calculations reveal that H3PO4and H2P2O6species are the dominant phosphate species on the P/CeO2catalysts under the experimental conditions. The reduction/oxidation half-cycles (RHC/OHC) were investigated using in situX-ray absorption near-edge structure for Ce L3-edge, ultraviolet–visible, and infrared (IR) spectroscopies together with online analysis of outlet products (operandospectroscopy). The Ce4+(OH–) species, possibly adjacent to the phosphate species, are reduced by NO + NH3to produce N2, H2O, and Ce3+species (RHC). The Ce3+species is reoxidized by aqueous O2(OHC). The results from IR spectroscopy suggest that the RHC initiates with the reaction between NO and Ce4+(OH–) to yield Ce3+and gaseous HONO, which then react with NH3to produce N2and H2O via NH4NO2intermediates.

In this article, we propose a novel solution for nonconvex problems of multiple variables, especially for those typically solved by an alternating minimization (AM) strategy that splits the original optimization problem into a set of subproblems corresponding to each variable and then iteratively optimizes each subproblem using a fixed updating rule. However, due to the intrinsic nonconvexity of the original optimization problem, the optimization can be trapped into a spurious local minimum even when each subproblem can be optimally solved at each iteration. Meanwhile, learning-based approaches, such as deep unfolding algorithms, have gained popularity for nonconvex optimization; however, they are highly limited by the availability of labeled data and insufficient explainability. To tackle these issues, we propose a meta-learning based alternating minimization (MLAM) method that aims to minimize a part of the global losses over iterations instead of carrying minimization on each subproblem, and it tends to learn an adaptive strategy to replace the handcrafted counterpart resulting in advance on superior performance. The proposed MLAM maintains the original algorithmic principle, providing certain interpretability. We evaluate the proposed method on two representative problems, namely, bilinear inverse problem: matrix completion and nonlinear problem: Gaussian mixture models. The experimental results validate the proposed approach outperforms AM-based methods.

Tubular epithelial cells (TECs) exposed to hypoxia incite tubulointerstitial inflammation (TII), while the exact mechanism is unclear. In this study, we identified that hypoxia evoked tubule injury as evidenced by tubular hypoxia-inducible factor-1α and kidney injury molecule-1 (KIM-1) expression and that renal small extracellular vesicle (sEV) production was increased with the development of TII after ischemia-reperfusion injury (IRI). Intriguingly, KIM-1-positive tubules were surrounded by macrophages and co-localized with sEVs. In vitro, KIM-1 expression and sEV release were increased in hypoxic TECs and the hypoxia-induced inflammatory response was ameliorated when KIM-1or Rab27a, a master regulator of sEV secretion, was silenced. Furthermore, KIM-1 was identified to mediate hypoxic TEC-derived sEV (Hypo-sEV) uptake by TECs. Phosphatidylserine (PS), a ligand of KIM-1, was present in Hypo-sEVs as detected by nanoflow cytometry. Correspondingly, the inflammatory response induced by exogenous Hypo-sEVs was attenuated when KIM-1was knocked down. In vivo, exogenous-applied Hypo-sEVs localized to KIM-1-positive tubules and exacerbated TII in IRI mice. Our study demonstrated that KIM-1 expressed by injured tubules mediated sEV uptake via recognizing PS, which participated in the amplification of tubule inflammation induced by hypoxia, leading to the development of TII in ischemic acute kidney injury.

Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis. However, the effect of lncRNA on chemoresistance and RNA alternative splicing remains largely unknown. In this study, we identified a novel lncRNA, CACClnc, which was upregulated and associated with chemoresistance and poor prognosis in colorectal cancer (CRC). CACClnc promoted CRC resistance to chemotherapy via promoting DNA repair and enhancing homologous recombination in vitro and in vivo. Mechanistically, CACClnc specifically bound to Y-box binding protein 1 (YB1, a splicing factor) and U2AF65 (a subunit of U2AF splicing factor), promoting the interaction between YB1 and U2AF65, and then modulated alternative splicing (AS) of RAD51mRNA, and consequently altered CRC cell biology. In addition, expression of exosomal CACClnc in peripheral plasma of CRC patients can effectively predict the chemotherapy effect of patients before treatment. Thus, measuring and targeting CACClnc and its associated pathway could yield valuable insight into clinical management and might ameliorate CRC patients’ outcomes.

The LLC resonant converter has been widely used in the power supply industry, such as server power, TV power, and adapter, because this converter can realize the zero-voltage switching (ZVS) at the power mosfets of the primary side. Thus, the switch losses can be decreased, and the conversion efficiency can also be improved. The electric vehicle (EV) charger has been recently widely used in research and development. However, designing LLC resonant converters for the wide battery voltage range is difficult because this converter is usually utilized in pulse-frequency modulation (PFM) to regulate the output voltage. This converter will also be limited to the low operating frequency range for the high conversion efficiency due to the switching frequency. By contrast, the phase-shift modulation (PSM) control for the wide output voltage range has been used at LLC resonant converters. However, the ZVS will be lost due to the lagging leg of the LLC resonant converter when the phase-shift angle is remarkably excessive. The burst-mode control has also been proposed for the converter to regulate the output voltage and maintain high conversion efficiency at light-load conditions. Therefore, this article utilized the combination of PFM, PSM, and burst-mode control for the LLC resonant converter operating at the wide output voltage range for EV charge applications. Furthermore, this article proposed a synchronous rectification advance on-time control for PFM control, which can help address the ZVS at the lagging leg when the phase-shift angle is excessive. Detailed analysis and design of this control method are also described. The performance evaluation of the proposed LLC resonant converter with hybrid control was finally realized under the following conditions: 3.75 kW, dc input voltage of 400 VDC, dc output voltage of 75–475 VDC, and maximum conversion efficiency around 97%.

This article proposes a configurable supply mechanism in the power stage to simultaneously improve the load transient response and power conversion efficiency. The power stage, comprising a dc–dc converter and an auxiliary power circuit (APC), can be organized depending on the variable load conditions. During step-load changes, the APC can provide an additional charging or discharging current to the output capacitance of the dc–dc converter to compensate for any differences between the load current and inductor current. Meanwhile, two auxiliary transient transistors are employed to immediately adjust the output level of the error amplifier because the peak current-mode control is used in the dc–dc converter. Thus, the recovery time and output transient ripple are enhanced significantly. At the steady state, the APC is inactivated; thus, the conversion efficiency of the dc–dc converter does not degenerate. Above medium loads, only the dc–dc converter is activated to deliver adequate power with high efficiency. At light loads, the APC acts as a linear regulator to take over the energy delivery scheme because power consumption is reduced effectively while the output voltage is kept. Therefore, the hybrid operation can guarantee improvements in load transient response and power conversion efficiency at light loads. The proposed converter was fabricated with 0.35-μm CMOS technology. The experimental results showed that the recovery times for 450-mA step-down and step-up loads are 1.6 and 2.0 μs, respectively. Comparing to when the transient mode is disabled, the recovery time of the output voltage is improved by over ten times when the transient mode is enabled. Further, the efficiency improvements with the proposed method at load current of 20 mA under the output voltages of 2.5 V and 1.8 V are 13.8% and 4.9%, respectively.

Hot deformation behavior and microstructure of 60NiTi alloy during hot compressive deformation were investigated using Gleeble−3500 thermal simulation test machine in the temperature range of 500−650 °C and strain rate range of 0.001−1 s−1. The constitutive equation of hot compression was constructed and the hot processing maps were plotted. When the compression temperature rose or the strain rate declined, the peak stress reduced. The hot deformation activation energy was calculated as 327.89 kJ/mol, and the proper hot working parameters of compression temperature of 600−650 °C and strain rate of 0.005−0.05 s−1were obtained. The recrystallization degree increased with increasing compression temperature. When the strain rate increased, both dislocation density and number of twins were improved, and the Ni3Ti phase tended to aggregate. Ni3Ti precipitation phase was beneficial to inducing dynamic recrystallization of the 60NiTi alloy. The dynamic recovery, dynamic recrystallization and twinning took place during hot compressive deformation of the 60NiTi alloy.

A novel central hole-expansion phenomenon is identified, in which the cation-exchange resin is pyrolyzed in a mixed atmosphere of nitrogen and oxygen at 400–500 °C. In this reaction, the reaction path is predictable and always starts from the center of the resin particle to form a central hole, then continues and expands around the hole, finally forming a uniformly distributed hole group; the particle surface remains intact. Analysis shows that this formation mode is due to the different reaction paths of sulfonic groups between the surface and interior of the particle, caused by the temperature difference. On the surface, transformation reactions happen at high temperatures (410–500 °C) to form stable organic sulfur structures, while decomposition occurs inside the particle at a relatively low temperature (<410 °C) and promotes complete pyrolysis of the copolymer matrix to form holes.

Co2Co4(SiW10O37)2/Fe2O3composite photocatalysts were created by chemical synthesis. FTIR, UV–Vis, XRD, and SEM were used to characterise the materials. The result demonstrates that polyoxometalates have a massive structure and that ferric oxide is tightly coupled with polyoxometalates in the composites. By varying the pH and amount of Fe2O3, the optimal synthesis conditions for the composites were determined. The catalytic degradation of methyl orange solution was performed in the presence of a xenon lamp (18.085 mW/cm2). When the pH was set to one, the composite had the best decomposition effect on methyl orange, with a decomposition efficiency of 76.2%. Simultaneously, the possible mechanism of the photocatalytic process was investigated. The photocatalytic process was almost completely inhibited after the photogenerated holes were masked by triethanolamine. The results indicate that photogenerated holes are the deciding factor in the composites’ photocatalytic effect. They also measured the composites’ band gap width with UV–Vis spectroscopy and cyclic-voltammetry, and the likely photocatalytic mechanism was thoroughly investigated.

Fatty acid synthase (FASN), a sole cytosolic enzyme responsible for de-novo lipid synthesis, is overexpressed in cancer but not in normal non-lipogenic tissues. FASN has been targeted, albeit no such inhibitor has been approved. Proton pump inhibitors (PPIs), approved for digestive disorders, were found to inhibit FASN with anticancer activities in attempting to repurpose Food and Drug Administration-approved drugs. Indeed, PPI usage benefited breast cancer patients and increased their response rate. Due to structural similarity, we thought that their metabolites might extend anticancer effects of PPIs by inhibiting FASN. Here, we tested this hypothesis and found that 5-hydroxy lansoprazole sulfide (5HLS), the end lansoprazole metabolite, was more active than lansoprazole in inhibiting FASN function and regulation of NHEJ repair of oxidative DNA damage via PARP1. Surprisingly, 5HLS inhibits the enoyl reductase, whereas lansoprazole inhibits the thioesterase of FASN. Thus, PPI metabolites may contribute to the lasting anticancer effects of PPIs by inhibiting FASN.

The LLC converter has been widely used in the power supply industry for its high conversion efficiency. When the output load is low, the LLC resonant converter will substantially increase the operating frequency, thereby reducing the conversion efficiency and exceeding the limited operating frequency of the specification. Thus, burst-mode control is applied to increase the ability of regulation at light-load conditions. Even so, the switching period of power switches still occurs at a high switching frequency. Burst-mode control will also result in an extremely low-frequency output voltage ripple. In this study, a valley switching control (VSC) for the LLC resonant converter at light-load conditions is proposed. The VSC control strategy maintains the output voltage by modulating the pulsewidth signals of drivers and achieves valley switching by modulating the switching frequency. Thus, the VSC strategy can reduce the operating frequency compared with the frequency modulation strategy. Compared with burst-mode operations, the proposed VSC effectively reduces the switching loss and has the advantage of high-frequency output voltage ripple. The VSC increases the efficiency and the power quality of the converter. Detailed analysis and design of the proposed method are described. Experimental results are recorded for a prototype converter with a dc input voltage of 400 $V_{\mathrm {DC}}$ , an output voltage of $48~V_{\mathrm {DC}}$ , and an output current of 12.5 A.

A Johann-type X-ray spectrometer was successfully developed at the hard X-ray branch (in-vacuum undulator with a 24-mm periodic length) of the energy material beamline (E-line) at the Shanghai Synchrotron Radiation Facility (SSRF). This spectrometer was utilized to implement X-ray emission spectroscopy (XES), high-energy resolution fluorescence-detected X-ray absorption spectroscopy (HERFD-XAS), and resonant inelastic X-ray scattering. Seven spherically bent crystals were positioned on the respective vertical 500-mm-diameter Rowland circles, adopting an area detector to increase the solid angle to 1.75%of 4 πsr, facilitating the study of low-concentrate systems under complex reaction conditions. Operated under the atmosphere pressure, the spectrometer covers the energy region from 3.5 to 18 keV, with the Bragg angle ranging from 73∘to 86∘during vertical scanning. It offers a promised energy resolution of sub-eV (XES) and super-eV (HERFD-XAS). Generally, these comprehensive core-level spectroscopy methods based on hard X-rays at the E-line with an extremely high photon flux can meet the crucial requirements of a green energy strategy. Moreover, they provide substantial support for scientific advances in fundamental research.

Tracking liver polarity with noninvasive and dynamic imaging techniques is helpful to better understand the non-alcoholic fatty liver (NAFL). Herein, a novel near-infrared (NIR) fluorescent probe Cy-Mpis constructed using a “symmetry collapse” strategy. The structure modification leads to the conversion of locally excited state fluorescence to charge transfer state fluorescence. Cy-Mpemits at near-infrared (NIR) wavelengths with high photostability as well as a large Stokes shift. Cy-Mpexhibits a ratiometric response to polarity, providing more accurate analysis of intracellular polarity viathe built-in internal reference correction. Most importantly, the in vivo studies indicate that Cy-Mpcan accumulate in the liver and the decreased polarity in the liver of mice with NAFL is verified by the ratiometric imaging, implying the great potential of Cy-Mpin the diagnosis of NAFL.

This letter proposes a learning aided gradient descent (LAGD) algorithm to solve the weighted sum rate (WSR) maximization problem for multiple-input single-output (MISO) beamforming. The proposed LAGD algorithm directly optimizes the transmit precoder through implicit gradient descent based iterations, at each of which the optimization strategy is determined by a neural network, and thus, is dynamic and adaptive. At each instance of the problem, this network is initialized randomly, and updated throughout the iterative solution process. Therefore, the LAGD algorithm can be implemented at any signal-to-noise ratio (SNR) and for arbitrary antenna/user numbers, does not require labelled data or training prior to deployment. Numerical results show that the LAGD algorithm can outperform of the well-known WMMSE algorithm as well as other learning-based solutions with a modest computational complexity. Our code is available at https://github.com/XiaGroup/LAGD.

Metal–organic frameworks (MOFs) combine high guest-accessible porosity with high chemical versatility, which predestines tailor-making porous materials to overcome challenges in efficient next-generation gas separation processes. Adsorptive gating is an interesting material feature that enhances sorption selectivity, while its rational design is still beyond our knowledge. Herein, we report on a model system to explore the key factors of induced gating controlled by the implementation of conformationally flexible side chains at the linkers of a honeycomb-like, structurally rigid MOF, namely, Zn2(2,5-difunctionalized-1,4-benzendicarboxylate)2(4,4′-bipyridine). The sorption and separation properties of C2H2and CO2were selected as the study case, and ideal adsorbed solution theory (IAST) selectivities, isosteric enthalpies of adsorption, Henry constants, breakthrough experiments, and simulations of dynamic properties were correlated with the linker functionalization. Two dominating factors that determine gating properties are identified: polarizability and sorption site accessibility. These factors are accessible through linker functionalization, and we show that adsorption strength differences can be influenced linearly within 1 order of magnitude, while breakthrough experiments show a selectivity increase toward C2H2, ranging from 4.1 to 10.9. The results suggest transfer to other MOFs toward extrinsic gating for sophisticated modulation of their sorption selectivity.

We herein report an unprecedented pathway to access γ-lactams using acetonitrile analogues as coupling partners without oxidants, ligands, and Lewis acids. The reaction undergoes Rh-catalyzed C(sp2)–H addition to carbon-bound nitriles with the aid of an amide traceless auxiliary followed by an annulation sequence, featuring a broad substrate scope, good functional group tolerance, and excellent chemo/stereoselectivity. Scale-up reactions and late-stage derivatizations highlight the potential synthetic utility of this methodology. A plausible mechanism is proposed based on mechanistic investigations.

In China, health screening has become common, although colonoscopy is not always available or acceptable. We sought to develop a prediction model of colorectal cancer (CRC) for health screening population based on readily available clinical data to reduce labor and economic costs.

Keggin-type phosphomolybdic acid (PMo12O40), treated with pyridine (Py), forms a crystalline material (PyPMo-HT) following heat treatment under an inert gas flow at ∼420 °C. Although this material is known to have attractive catalytic properties for gas-phase oxidation, the origin of this catalytic activity requires clarification. In this study, we investigated the crystal structure of PyPMo-HT. PyPMo-HTcomprises a one-dimensional array of Keggin units and pyridinium cations (HPy), with an HPy/Keggin unit ratio of ∼1.0. Two oxygen atoms were removed from the Keggin unit during crystal structure transformation, which resulted in an electron being localized on the Mo atom in close contact with the adjacent Keggin unit. Upon the introduction of molecular oxygen, electron transfer from this Mo atom resulted in the formation of an electrophilic oxygen species that bridged two Keggin units. The electrophilic oxygen species acted as a catalytically active oxygen species, as confirmed by the selective oxidation of propylene. PyPMo-HTshowed excellent catalytic activity for the selective oxidation of methacrolein, with the methacrylic acid yield being superior to that obtained with PMo12O40and comparable to that obtained with an industrial Keggin-type polyoxometalate (POM) catalyst. The oxidation catalysis observed over PyPMo-HTprovides a deeper understanding of POM-based industrial catalytic processes.

eIF3a (eukaryotic translation initiation factor 3a), a subunit of the eIF3 complex, has been suggested to play a regulatory role in protein synthesis and in cellular response to DNA-damaging treatments. S6K1 is an effector and a mediator of mTOR complex 1 (mTORC1) in regulating protein synthesis and integrating diverse signals into control of cell growth and response to stress. Here, we show that eIF3a regulates S6K1 activity by inhibiting mTORC1 kinase via regulating Raptor synthesis. The regulation of Raptor synthesis is via eIF3a interaction with HuR (human antigen R) and binding of the eIF3a-HuR complex to the 5ʹ-UTR of Raptor mRNA. Furthermore, mTORC1 may mediate eIF3a function in cellular response to cisplatin by regulating synthesis of NER proteins and NER activity. Taken together, we conclude that the mTOR signaling pathway may also be regulated by translational control and mediate eIF3a regulation of cancer cell response to cisplatin by regulating NER protein synthesis.

A multifunctional metal–organic framework, (Hdmbpy)[Dy(H2dobdc)2(H2O)]·3H2O (Dy-MOF, H4dobdc = 2,5-dihydroxyterephthalic acid, dmbpy = 4,4′-dimethyl-2,2′-bipyridine), was synthesized and structurally characterized. The metal center DyIIIis connected by four carboxyl groups to form the [Dy2(CO2)4] binuclear nodes, which are further interconnected by eight separate H2dobdc2–ligands to form a three-dimensional (3D) framework including hydrophilic triangular channels and abundant hydrogen-bonding networks. Dy-MOFhas good stability in aqueous solution as well as in harsh acidic or alkaline solutions (pH range: 2.0–12.0). Furthermore, the luminescence signal of Dy-MOFundergoes a visualized color change as the acidity of the solution alters, which is the typical behavior of pH ratiometric probe. At a 100% relative humidity, Dy-MOFexhibits a high proton conductivity σ (1.70 × 10–4S cm–1at 303 K; 1.20 × 10–3S cm–1at 343 K) based on the proton hopping mechanism, which can be classified as a superionic conductor with σ exceeding 10–4S cm–1. Additionally, the ferromagnetic interaction and magnetic relaxation behavior are simultaneously achieved in Dy-MOF. Herein, the combination of luminescence sensing, magnetism, and proton conduction in a single-phase 3D MOF may offer great potential applications in smart multitasking devices.

This study aims to get the medical management of acupuncture and moxibustion in the countries and regions where the society members of World Federation of Acupuncture-Moxibustion Societies (WFAS) are located, including the educational background of acupuncture and moxibustion practitioners and the local clinical practice of acupuncture and moxibustion, and the demands of the content and evidence types of Clinical Practice Guidelines (CPGs) of acupuncture and moxibustion in accordance with WFAS standards, so as to provide requirements and reference principles for the development of CPGs of acupuncture and moxibustion in accordance with WFAS standards.

Literature data based on the water gas shift (WGS) reaction have been analyzed using statistical methods based on machine learning (ML). Our ML approach, which considers elemental features as input representations rather than the catalyst compositions, was successfully applied, and new promising catalyst candidates for future research were proposed.Literature data based on the water gas shift (WGS) reaction have been analyzed using statistical methods based on machine learning (ML). Our ML approach that considers elemental features as input representations rather than the catalyst compositions, was successfully applied, and novel promising catalyst candidates for future studies were proposed.

Different sizes of γ-Fe2O3nanoparticles (4–19 nm) were prepared by thermal decomposition of iron oleate and carburized in three different gas atmosphere of 5%CO/He, 5%CO/10%H2/He and 5%CO/20%H2/He at 350 °C. The carburization process and phase transformation of γ-Fe2O3nanoparticles were investigated by in-situXRD, Raman spectroscopy, CO-TPR and TEM. The results show that χ-Fe5C2and θ-Fe3C phases with a stable ratio formed after carburization. The time to complete carburization was shortened for increasing sizes of γ-Fe2O3particles under the same carburization atmosphere. While the smaller γ-Fe2O3particles showed more residual carbon on the surface, which can inhibit the carburization process. The relative content of θ-Fe3C increased with the increase of the size of γ-Fe2O3nanoparticles. For γ-Fe2O3nanoparticles with the same sizes, the time to complete carburization in different atmospheres was firstly shortened and then slightly lengthened with the increase of H2partial pressure, while the relative content of θ-Fe3C increased with the increase of H2partial pressure. By adjusting the particle size of γ-Fe2O3and the carburization atmosphere, the mixed phases of χ-Fe5C2and θ-Fe3C can be optimized.

This qualitative study describes the psychological experience of patients hospitalized with COVID-19. These patients went through 3 psychological stages: extremely uncertainties during the initial diagnostic stage, complicated feelings of negativity during the treatment stage, and positive growth in the recovery stage. It is important for nurses to provide holistic care.

The cost of Pt is currently lower than that of Pd and Rh, however, Pt-based three-way catalysts (TWCs) have attracted less attention than Pd- and Rh-based TWCs. Consequently, the fundamental understanding of the properties of Pt-based TWCs remains insufficient. Herein, we demonstrate the effect of oxygen storage materials (OSMs), including CeO2and CeO2–ZrO2solid-solutions having different ceria contents (20%, 45%, and 66%), on the three-way catalysis performance of Pt/OSMs using various spectroscopic observations in combination with kinetic studies. In comparative assessments of powdered and monolithic (honeycomb) catalysts, fresh Pt/OSM(100%CeO2) and aged Pt/OSM(66%CeO2) exhibited the highest NO conversion among their corresponding series, showing that Pt/OSM(66%CeO2) is the most promising and stable among the TWCs. In situCO adsorption infrared (IR) spectroscopy and X-ray photoelectron spectroscopy (XPS) revealed that the Pt0species loaded on OSMs having a higher ceria content were more electron-deficient. OperandoIR and kinetic investigations suggested that increasing the ceria content in fresh Pt/OSMs enhanced not only the formation of nitrite species and their reactivity toward CO but also the resistance to CO poisoning during NO–CO reactions. In situX-ray absorption spectroscopy (XAS) indicated that both Ce and Pt species in Pt/OSM catalysts are involved in NO–CO reactions through their redox cycles. In situXAS in combination with X-ray diffraction (XRD) measurements revealed that the hydrothermal ageing treatment resulted in the aggregation of Pt particles and lattice contraction of CeO2in Pt/OSMs, causing severe degradation of the redox ability of Pt and Ce species and reducing the promoting effect of ceria on the formation of nitrites and their reactivity toward CO.

ObjectiveMultiple clinical similarities exist between IgG4-related sclerosing cholangitis (IgG4-SC) and primary sclerosing cholangitis (PSC), and while gut dysbiosis has been extensively studied in PSC, the role of the gut microbiota in IgG4-SC remains unknown. Herein, we aimed to evaluate alterations of the gut microbiome and metabolome in IgG4-SC and PSC.DesignWe performed 16S rRNA gene amplicon sequencing of faecal samples from 135 subjects with IgG4-SC (n=34), PSC (n=37) and healthy controls (n=64). A subset of the samples (31 IgG4-SC, 37 PSC and 45 controls) also underwent untargeted metabolomic profiling.ResultsCompared with controls, reduced alpha-diversity and shifted microbial community were observed in IgG4-SC and PSC. These changes were accompanied by differences in stool metabolomes. Importantly, despite some common variations in the microbiota composition and metabolic activity, integrative analyses identified distinct host–microbe associations in IgG4-SC and PSC. The disease-associated genera and metabolites tended to associate with the transaminases in IgG4-SC. Notable depletion of Blautiaand elevated succinic acid may underlie hepatic inflammation in IgG4-SC. In comparison, potential links between the microbial or metabolic signatures and cholestatic parameters were detected in PSC. Particularly, concordant decrease of Eubacteriumand microbiota-derived metabolites, including secondary bile acids, implicated novel host–microbial metabolic pathways involving cholestasis of PSC. Interestingly, the predictive models based on metabolites were more effective in discriminating disease status than those based on microbes.ConclusionsOur data reveal that IgG4-SC and PSC possess divergent host–microbe interplays that may be involved in disease pathogenesis. These data emphasise the uniqueness of IgG4-SC.

Introduction:Acute kidney injury (AKI) is a major public health problem worldwide. However, there is no definitive therapies to treat established AKI. In this study, we used FG-4592 to induce hypoxia inducible factor (HIF) expression in cells and then explored whether the extracellular vesicles (EVs) secreted by HIF-upregulated cells could alleviate ischemia/reperfusion injury (IRI)-induced AKI. Methods:FG-4592/HK2-EVs and FG-4592/HEK293-EVs were prepared by treating HK2 or HEK293 cells with FG-4592 for 24 h, respectively. HK2 cells under hypoxia were treated with FG-4592/HK2-EVs or FG-4592/HEK293-EVs to observe the therapeutic effect of EVs on H/R-induced apoptosis and inflammation. Mice were treated with FG-4592/HEK293-EVs after IRI to observe whether FG-4592/HEK293-EVs treatment could alleviate ischemic AKI. Results:The expression of HIF was induced by FG-4592 in a dose-dependent manner in HK2 and HEK293 cells under normoxia. In vitro, FG-4592/HK2-EVs and FG-4592/HEK293-EVs inhibited apoptosis and inflammation induced by H/R. In vivo, treatment with FG-4592/HEK293-EVs significantly ameliorated renal tubular injury and inflammation caused by IRI. In addition, the expression of HIF-1α in cells and kidneys was significantly downregulated by FG-4592/HK2-EVs and FG-4592/HEK293-EVs treatment. Conclusion:This study demonstrated that EVs derived from HK2 or HEK293 cells after FG-4592 treatment could alleviate renal tubular injury and inflammation, suggesting a novel therapeutic role of FG-4592/EVs in the treatment of AKI.

By using the open-source software OpenFOAM and the grid generation tool the integrated computer engineering and manufacturing code for computational fluid dynamics (ICEM CFD), a computational fluid dynamics-computational structural dynamics (CFD-CSD) coupling model is established. The dynamic response and the liquefaction of the seabed around the composite bucket foundation of the offshore wind turbines in the Xiangshui area of Jiangsu Province are investigated. The pore water pressure, the effective stress, the liquefaction depth and the anti-liquefaction effect of the overlying stones are analyzed. It is shown that the seabed around the composite bucket foundation will be liquefied under 50 year return waves, the liquefaction width is approximately 1/3 of the wavelength, and the maximum liquefaction depth is approximately 1/4 of the wave height. In addition, the overlying stones provide an effective anti-liquefaction method. Thicker, less porous overlying stones have a better anti-liquefaction effect.

Migraine is one of the most common and highest burdens of disease. As a primary cerebral dysfunction illness, migraine might exhibit other system-related symptoms, including vestibular and cochlear symptoms. With the publication of the diagnostic criteria of vestibular migraine, the link between migraine and vestibular symptoms became clear. However, the relationship between migraine and cochlear symptoms is far from straightforward. Therefore, we focus on the correlation between migraine and deafness, sudden sensorineural hearing loss, acute tinnitus, and chronic tinnitus to better understand the relationship between migraine and cochlear symptoms.

Aim: The aim of this study is to determine the potential of the waist-height ratio (WHtR) and body mass index (BMI) as predictors of non-communicable disease (NCD) risk factors. Subjects and methods: A retrospective study using data from the 2016 National NCD survey (STEPS). A total of 3808 data points were retrieved including sociodemographic factors, anthropometric measurements, NCD prevalence and risk factors. Multiple logistic and linear regression was applied for analysis. Results: Men (OR = 0.77, 95% CI: 0.63, 0.95), aged ≥ 45 years (OR = 4.24, 95% CI: 3.15, 0.97), of Malay ethnicity, with no formal schooling, and with existing hypertension and diabetes had significantly higher odds of having WHtR > 0.5. BMI ≥ 25 and BMI ≥ 30 are significantly associated with age group, ethnicity, education level, alcohol consumption, hypertension, diabetes and hypercholesterolaemia. Conclusion: Both WHtR and BMI were important predictors of NCD prevalence. These findings can contribute to the validity of the WHtR in clinical application and encourage the use of these anthropometric indices in clinical settings.