Search

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.