Electrical Polarity Modulation in V-Doped Monolayer WS2 for Homogeneous CMOS Inverters.

As demand for higher integration density and smaller devices grows, silicon-based complementary metal-oxide-semiconductor (CMOS) devices will soon reach their ultimate limits. 2D transition metal dichalcogenides (TMDs) semiconductors, known for excellent electrical performance and stable atomic structure, are seen as promising materials for future integrated circuits. However, controlled and reliable doping of 2D TMDs, a key step for creating homogeneous CMOS logic components, remains a challenge. In this study, a continuous electrical polarity modulation of monolayer WS2 from intrinsic n-type to ambipolar, then to p-type, and ultimately to a quasi-metallic state is achieved simply by introducing controllable amounts of vanadium (V) atoms into the WS2 lattice as p-type dopants during chemical vapor deposition (CVD). The achievement of purely p-type field-effect transistors (FETs) is particularly noteworthy based on the 4.7 at% V-doped monolayer WS2, demonstrating a remarkable on/off current ratio of 105. Expanding on this triumph, the first initial prototype of ultrathin homogeneous CMOS inverters based on monolayer WS2 is being constructed. These outcomes validate the feasibility of constructing homogeneous CMOS devices through the atomic doping process of 2D materials, marking a significant milestone for the future development of integrated circuits.

Prognostic significance of plasma SDF-1 in acute ischemic stroke patients with diabetes mellitus: the CATIS trial.

BACKGROUND AND OBJECTIVES: Evidence on the associations between baseline stromal cell-derived factor (SDF)-1 and clinical outcomes in acute ischemic stroke patients is lacking. The present study aimed to examine the relationship between plasma SDF-1 levels and clinical outcomes based on a large multicenter study of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). METHODS: Secondary analysis was conducted among 3,255 participants from the CATIS trial with a baseline measurement of plasma SDF-1 levels. We evaluated the associations between plasma SDF-1 levels and one-year recurrent stroke, cardiovascular events, and all-cause mortality using Cox regression models. We further investigated the prognostic effect of SDF-1 on clinical outcomes in patients with different characteristics. RESULTS: Higher plasma SDF-1 levels were not associated with recurrent stroke, cardiovascular events, and all-cause mortality at one-year after ischemic stroke (all P trend ≥ 0.05). There were significant interactions between plasma SDF-1 levels and history of diabetes mellitus on recurrent stroke (P = 0.005), cardiovascular events (P = 0.007) and all-cause mortality (P = 0.04) at one year. In patients with diabetes mellitus, plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events after adjustment for confounders. For example, 1-SD higher log-SDF-1 was associated with a hazard ratio (95% confidence interval) of 1.65 (1.18-2.32) for recurrent stroke and 1.47 (1.08-1.99) for the cardiovascular events, but not all-cause mortality 1.36 (0.96-1.93) at one year. However, there were no associations between plasma SDF-1 and clinical outcomes in patients without diabetes mellitus (all P > 0.05). The addition of plasma SDF-1 to the conventional risk factors model significantly improved the risk prediction of all outcomes. Similarly, findings between elevated SDF-1 levels and two-year outcomes were found only in patients with diabetes mellitus. CONCLUSIONS: Elevated plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events only in ischemic patients with diabetes mellitus.

Lipoprotein(a) and functional outcome of acute ischemic stroke when discordant with low-density lipoprotein cholesterol.

BACKGROUND: Several studies have indicated that residual cardiovascular risk might be associated with elevated lipoprotein(a) [Lp(a)] even in the setting of controlled low-density lipoprotein cholesterol (LDL-C). We aimed to prospectively examine the association between Lp(a) and unfavorable functional outcome among patients with acute ischemic stroke when Lp(a) and LDL-C were discordant. METHODS: Based on samples from the Infectious Factors, Inflammatory Markers and Prognosis of Acute Ischemic Stroke study, 973 patients with baseline plasma Lp(a) levels were included. The primary outcome was the composite outcome of death or major disability (modified Rankin Scale score of 3-6) at 6 months. Logistic regression models were used to estimate the risk for the primary outcome. Discordance analyses were performed, using difference in percentile units (>10 units), to detect the relative risk when Lp(a) and LDL-C were discordant. RESULTS: In total, 201 (20.7%) participants experienced major disability or death at 6 months. The multivariable-adjusted odds ratio (OR) for the highest quartile was 1.88 [95% confidence interval (CI): 1.16-3.04] compared with the lowest quartile. Each 1-SD higher log-Lp(a) was associated with a 23% increased risk (95% CI: 2%-47%) for the primary outcome. Compared with the concordant group, the high Lp(a)/low LDL-C discordant group was associated with increased risk for the primary outcome (adjusted OR: 1.59, 95% CI: 1.01-2.52). CONCLUSIONS: Elevated plasma Lp(a) levels were associated with increased risk of major disability and death at 6 months. Discordantly high Lp(a)/low LDL-C was associated with an unfavorable functional outcome, supporting the predictive potential of plasma Lp(a) after ischemic stroke, especially when discordant with LDL-C. Key messages What is already known on this topic Previous studies have indicated that a positive association between increased lipoprotein(a) [Lp(a)] and cardiovascular disease risk remained even in patients who achieved controlled low-density lipoprotein cholesterol (LDL-C) levels. The findings of studies exploring the association between Lp(a) and unfavorable clinical outcomes of stroke were inconsistent, and whether Lp(a) can predict the risk of unfavorable functional outcome in stroke patients when Lp(a) and LDL-C levels are discordant remains unknown. What this study adds Elevated plasma Lp(a) levels were associated with increased risk of major disability and death at 6 months beyond LDL-C levels in acute ischemic stroke patients. How this study might affect research, practice, or policy The combination of LDL-C-lowering therapies and Lp(a)-lowering therapies may have better clinical efficacy for patients with ischemic stroke, and it is of great clinical interest to further explore this possibility in dedicated randomized trials.

Electrostatic Shaping of Magnetic Transition Regions in La_{0.7}Sr_{0.3}MnO_{3}.

We report a magnetic transition region in La_{0.7}Sr_{0.3}MnO_{3} with gradually changing magnitude of magnetization, but no rotation, stable at all temperatures below T_{C}. Spatially resolved magnetization, composition and Mn valence data reveal that the magnetic transition region is induced by a subtle Mn composition change, leading to charge transfer at the interface due to carrier diffusion and drift. The electrostatic shaping of the magnetic transition region is mediated by the Mn valence, which affects both magnetization by Mn^{3+}-Mn^{4+} double exchange interaction and free carrier concentration.

Circulating choline pathway nutrients and depression after ischemic stroke.

BACKGROUND AND PURPOSE: Choline pathway nutrients, including choline and betaine, are reported to exert antidepressant effects. However, there is little population-based evidence on the relationships between circulating choline and betaine and poststroke depression (PSD). We aimed to prospectively explore the associations between plasma choline and betaine and depression after ischemic stroke. METHODS: This study was based on the China Antihypertensive Trial in Acute Ischemic Stroke. A total of 612 participants with plasma choline and betaine concentrations were included in the analysis. The study outcome was depression 3 months after ischemic stroke. Logistic regression models were performed to estimate the relationships between plasma choline and betaine and the risk of PSD. Risk reclassification and calibration of models with choline or betaine were analyzed. RESULTS: Patients with PSD had lower choline and betaine levels than those without PSD (p < 0.05). Compared with tertile 1, the multivariable-adjusted odds ratios (95% CIs) for tertile 3 of choline and betaine were 0.54 (0.35-0.83) and 0.59 (0.38-0.92), respectively. Per 1 SD increase in choline or betaine was associated with a 25% (95% CI 9%-37%) or an 19% (95% CI 3%-32%) decreased risk of PSD, respectively. Furthermore, the addition of choline or betaine to the established risk factors model improved the risk reclassification for PSD, as shown by an increase in the net reclassification index and integrated discrimination improvement (all p < 0.05). CONCLUSIONS: Patients with elevated levels of choline and betaine had a lower risk of depression after acute ischemic stroke, suggesting the protective significance of choline pathway nutrients for PSD.

Inorganic nanomaterials with rapid clearance for biomedical applications.

Inorganic nanomaterials that have inherently exceptional physicochemical properties (e.g., catalytic, optical, thermal, electrical, or magnetic performance) that can provide desirable functionality (e.g., drug delivery, diagnostics, imaging, or therapy) have considerable potential for application in the field of biomedicine. However, toxicity can be caused by the long-term, non-specific accumulation of these inorganic nanomaterials in healthy tissues, preventing their large-scale clinical utilization. Over the past several decades, the emergence of biodegradable and clearable inorganic nanomaterials has offered the potential to prevent such long-term toxicity. In addition, a comprehensive understanding of the design of such nanomaterials and their metabolic pathways within the body is essential for enabling the expansion of theranostic applications for various diseases and advancing clinical trials. Thus, it is of critical importance to develop biodegradable and clearable inorganic nanomaterials for biomedical applications. This review systematically summarizes the recent progress of biodegradable and clearable inorganic nanomaterials, particularly for application in cancer theranostics and other disease therapies. The future prospects and opportunities in this rapidly growing biomedical field are also discussed. We believe that this timely and comprehensive review will stimulate and guide additional in-depth studies in the area of inorganic nanomedicine, as rapid in vivo clearance and degradation is likely to be a prerequisite for the future clinical translation of inorganic nanomaterials with unique properties and functionality.

Stable iridium dinuclear heterogeneous catalysts supported on metal-oxide substrate for solar water oxidation.

Atomically dispersed catalysts refer to substrate-supported heterogeneous catalysts featuring one or a few active metal atoms that are separated from one another. They represent an important class of materials ranging from single-atom catalysts (SACs) and nanoparticles (NPs). While SACs and NPs have been extensively reported, catalysts featuring a few atoms with well-defined structures are poorly studied. The difficulty in synthesizing such structures has been a critical challenge. Here we report a facile photochemical method that produces catalytic centers consisting of two Ir metal cations, bridged by O and stably bound to a support. Direct evidence unambiguously supporting the dinuclear nature of the catalysts anchored on α-Fe2O3 is obtained by aberration-corrected scanning transmission electron microscopy (AC-STEM). Experimental and computational results further reveal that the threefold hollow binding sites on the OH-terminated surface of α-Fe2O3 anchor the catalysts to provide outstanding stability against detachment or aggregation. The resulting catalysts exhibit high activities toward H2O photooxidation.

Enantiospecific Detection of D-Amino Acid through Synergistic Upconversion Energy Transfer.

D-amino acids (DAAs) are indispensable in regulating diverse metabolic pathways. Selective and sensitive detection of DAAs is crucial for understanding the complexity of metabolic processes and managing associated diseases. However, current DAA detection strategies mainly rely on bulky instrumentation or electrochemical probes, limiting their cellular and animal applications. Here we report an enzyme-coupled nanoprobe that can detect enantiospecific DAAs through synergistic energy transfer. This nanoprobe offers near-infrared upconversion capability, a wide dynamic detection range, and a detection limit of 2.2 µM, providing a versatile platform for in vivo noninvasive detection of DAAs with high enantioselectivity. These results potentially allow real-time monitoring of biomolecular handedness in living animals, as well as developing antipsychotic treatment strategies.

Ultrafine Titanium Monoxide (TiO1+x) Nanorods for Enhanced Sonodynamic Therapy.

Ultrasound (US)-triggered sonodynamic therapy (SDT) that enables noninvasive treatment of large internal tumors has attracted widespread interest. For improvement in the therapeutic responses to SDT, more effective and stable sonosensitizers are still required. Herein, ultrafine titanium monoxide nanorods (TiO1+x NRs) with greatly improved sono-sensitization and Fenton-like catalytic activity were fabricated and used for enhanced SDT. TiO1+x NRs with an ultrafine rodlike structure were successfully prepared and then modified with polyethylene glycol (PEG). Compared to the conventional sonosensitizer, TiO2 nanoparticles, the PEG-TiO1+x NRs resulted in much more efficient US-induced generation of reactive oxygen species (ROS) because of the oxygen-deficient structure of TiO1+x NR, which predominantly serves as the charge trap to limit the recombination of US-triggered electron-hole pairs. Interestingly, PEG-TiO1+x NRs also exhibit horseradish-peroxidase-like nanozyme activity and can produce hydroxyl radicals (•OH) from endogenous H2O2 in the tumor to enable chemodynamic therapy (CDT). Because of their efficient passive retention in tumors post intravenous injection, PEG-TiO1+x NRs can be used as a sonosensitizer and CDT agent for highly effective tumor ablation under US treatment. In addition, no significant long-term toxicity of PEG-TiO1+x NRs was found for the treated mice. This work highlights a new type of titanium-based nanostructure with great performance for tumor SDT.

NaCeF4:Gd,Tb Scintillator as an X-ray Responsive Photosensitizer for Multimodal Imaging-Guided Synchronous Radio/Radiodynamic Therapy.

Photosensitizers (PSs) that are directly responsive to X-ray for radiodynamic therapy (RDT) with desirable imaging abilities have great potential applications in cancer therapy. Herein, the cerium (Ce)-doped NaCeF4:Gd,Tb scintillating nanoparticle (ScNP or scintillator) is first reported. Due to the sensitization effect of the Ce ions, Tb ions can emit fluorescence under X-ray irradiation to trigger X-ray excited fluorescence (XEF). Moreover, Ce and Tb ions can absorb the energy of secondary electrons generated by X-ray to produce reactive oxide species (ROS) for RDT. With the intrinsic absorption of X-ray by lanthanide elements, the NaCeF4:Gd,Tb ScNPs also act as a computed tomography (CT) imaging contrast agent and radiosensitizers for radiotherapy (RT) sensitization synchronously. Most importantly, the transverse relaxation time of Gd3+ ions is shortened due to the doping of Ce and Tb ions, leading to the excellent performance of our ScNPs in T2-weighted MR imaging for the first time. Both in vitro and in vivo studies verify that our synthesized ScNPs have good performance in XEF, CT, and T2-weighted MR imaging, and a synchronous RT/RDT is achieved with significant suppression on tumor progression under X-ray irradiation. Importantly, no systemic toxicity is observed after intravenous injection of ScNPs. Our work highlights that ScNPs have potential in multimodal imaging-guided RT/RDT of deep tumors.

Nanoparticle-Embedded Electrospun Fiber-Covered Stent to Assist Intraluminal Photodynamic Treatment of Oesophageal Cancer.

Drug-eluting stents (DESs) are promising candidates for treating human oesophageal cancer. However, the use of DESs to assist photodynamic therapy (PDT) of orthotopic oesophageal tumors is not yet demonstrated to the best of current knowledge. Herein, through an electrospinning technology it is shown that oxygen-producing manganese dioxide nanoparticles are embedded into elelctrospun fibers, which are subsequently covered onto stents. Upon implantation, the nanoparticles are gradually released from the fibers and then diffuse into the nearby tumor tissue. Then, the hypoxic microenvironment can be effectively alleviated by reaction of MnO2 with the endogenous H2 O2 within the tumor. After demonstrating the excellent PDT efficacy of the stents in a conventional subcutaneous mouse tumor model, such stents are further used for PDT treatment in a rabbit orthotopic oesophageal cancer model by inserting an optical fiber into the tumor site. Greatly prolonged survival of rabbits is observed after such intraluminal PDT treatment. Taken together, this work shows that the fiber-covered stent as a nanoparticle delivery platform can enable effective PDT as a noninvasive treatment method for patients with advanced-stage oesophageal cancer.

Publisher Correction: Atomic scale imaging of magnetic circular dichroism by achromatic electron microscopy.

In Fig. 1 of the version of this Letter originally published, the word 'Subtract' was missing from the green box to the left of panel f. This has now been corrected in all versions of the Letter.

Atomic scale imaging of magnetic circular dichroism by achromatic electron microscopy.

In order to obtain a fundamental understanding of the interplay between charge, spin, orbital and lattice degrees of freedom in magnetic materials and to predict and control their physical properties1-3, experimental techniques are required that are capable of accessing local magnetic information with atomic-scale spatial resolution. Here, we show that a combination of electron energy-loss magnetic chiral dichroism 4 and chromatic-aberration-corrected transmission electron microscopy, which reduces the focal spread of inelastically scattered electrons by orders of magnitude when compared with the use of spherical aberration correction alone, can achieve atomic-scale imaging of magnetic circular dichroism and provide element-selective orbital and spin magnetic moments atomic plane by atomic plane. This unique capability, which we demonstrate for Sr2FeMoO6, opens the door to local atomic-level studies of spin configurations in a multitude of materials that exhibit different types of magnetic coupling, thereby contributing to a detailed understanding of the physical origins of magnetic properties of materials at the highest spatial resolution.

Effect of Oxygen Interstitial Ordering on Multiple Order Parameters in Rare Earth Ferrite.

Oxygen interstitials and vacancies play a key role in modulating the microstructure and properties of nonstoichiometric oxide systems, such as those used for superconductors and multiferroics. Key to understanding the tuning mechanisms resulting from oxygen doping is a knowledge of the precise positions of these lattice defects, and of the interaction both between these defects and with many order parameters. Here, we report how such information can, for the first time, be obtained from a sample of LuFe_{2}O_{4.22} using a range of techniques including advanced electron microscopy, atomic-resolution spectroscopy, and density functional theory calculations. The results provide quantitative atomic details of the crystal unit cell, together with a description of the ferroelastic, ferroelectric, and ferromagnetic order parameters. We elucidate also the interaction between these order parameters and the positions of the oxygen interstitials in the oxygen-enriched sample. The comprehensive analysis of oxygen interstitial ordering provides insights into understanding the coupling among different degrees of freedom in rare earth ferrites and demonstrates that oxygen content regulation is a powerful tool for tuning the microstructure and properties for this class of quantum material.

Coxsackievirus B3 induces the formation of autophagosomes in cardiac fibroblasts both in vitro and in vivo.

Coxsackievirus group B (CVB) is one of the common pathogens that cause myocarditis and cardiomyopathy. Evidence has shown that CVB replication in cardiomyocytes is responsible for the damage and loss of cardiac muscle and the dysfunction of the heart. However, it remains largely undefined how CVB would directly impact cardiac fibroblasts, the most abundant cells in human heart. In this study, cardiac fibroblasts were isolated from Balb/c mice and infected with CVB type 3 (CVB3). Increased double-membraned, autophagosome-like vesicles in the CVB3-infected cardiac fibroblasts were observed with electron microscope. Punctate distribution of LC3 and increased level of LC3-II were also detected in the infected cardiac fibroblasts. Furthermore, we observed that the expression of pro-inflammatory cytokines, IL-6 and TNF-α, was increased in the CVB3-infected cardiac fibroblasts, while suppressed autophagy by 3-MA and Atg7-siRNA inhibited cytokine expression. Consistent with the in vitro findings, increased formation of autophagosomes was observed in the cardiac fibroblasts of Balb/c mice infected with CVB3. In conclusion, our data demonstrated that cardiac fibroblasts respond to CVB3 infection with the formation of autophagosomes and the release of the pro-inflammatory cytokines. These results suggest that the autophagic response of cardiac fibroblasts may play a role in the pathogenesis of myocarditis caused by CVB3 infection.

3D Quantification of Low-Coordinate Surface Atom Density: Bridging Catalytic Activity to Concave Facets of Nanocatalysts in Fuel Cells.

A protocol to quantify the distribution of surface atoms of concave nanocatalysts according to their coordination number is proposed. The 3D surface of an Au@Pd concave nanocube is reconstructed and segmented. The crystallographic coordinates and low-coordinate surface atom densities of the concave facets are determined. The result shows that 32% of the surface atoms are low-coordinated, which may contribute to the high activity.

Rhenium-188 Labeled Tungsten Disulfide Nanoflakes for Self-Sensitized, Near-Infrared Enhanced Radioisotope Therapy.

Radioisotope therapy (RIT), in which radioactive agents are administered or implanted into the body to irradiate tumors from the inside, is a clinically adopted cancer treatment method but still needs improvement to enhance its performances. Herein, it is found that polyethylene glycol (PEG) modified tungsten disulfide (WS2 ) nanoflakes can be easily labeled by (188) Re, a widely used radioisotope for RIT, upon simple mixing. Like other high-Z elements acting as radiosensitizers, tungsten in the obtained (188) Re-WS2 -PEG would be able to absorb ionization radiation generated from (188) Re, enabling ''self-sensitization'' to enhance the efficacy of RIT as demonstrated in carefully designed in vitro experiments of this study. In the meanwhile, the strong NIR absorbance of WS2 -PEG could be utilized for NIR light-induced photothermal therapy (PTT), which if applied on tumors would be able to greatly relieve their hypoxia state and help to overcome hypoxia-associated radioresistance of tumors. Therefore, with (188) Re-WS2 -PEG as a multifunctional agent, which shows efficient passive tumor homing after intravenous injection, in vivo self-sensitized, NIR-enhanced RIT cancer treatment is realized, achieving excellent tumor killing efficacy in a mouse tumor model. This work presents a new concept of applying nanotechnology in RIT, by delivering radioisotopes into tumors, self-sensitizing the irradiation-induced cell damage, and modulating the tumor hypoxia state to further enhance the therapeutic outcomes.

Efficacy and safety of empagliflozin as add-on to metformin for type 2 diabetes: a systematic review and meta-analysis.

PURPOSE: To assess the efficacy and safety of empagliflozin (EMPA) as add-on to metformin (MET) in patients with type 2 diabetes mellitus (T2DM). METHODS: We searched PubMed, Embase, Medline, OVID, Cochrane Library and Web of Science. Randomized controlled trials of EMPA as add-on to MET for T2DM were included. Two investigators independently selected studies, extracted data and assessed the risk of bias. A meta-analysis was conducted by using RevMan 5.3 software and Stata 12 software. RESULTS: Seven trials including 4256 patients were analysed. Compared with placebo, two different doses of EMPA significantly reduced glycated haemoglobin (HbA1c) [10 mg: weighted mean difference (WMD) -0.57 %; 95 % confidence interval (CI) -0.65 to -0.49 %, P < 0.00001; 25 mg: WMD -0.65 %; 95 % CI -0.72 to -0.57 %, P < 0.00001]. Compared with active comparators (two sitagliptin, one linagliptin and one glimepiride), 10 mg of EMPA provided a similar reduction in HbA1c [WMD -0.10 %; 95 % CI -0.23 to 0.03 %, P = 0.13], while 25 mg of EMPA provided a significantly greater reduction in HbA1c [WMD -0.13 %; 95 % CI -0.20 to -0.06 %, P = 0.0005]. In addition, EMPA as add-on to MET also had a favourable effect on body weight and blood pressure. The risk of hypoglycaemia in the EMPA group was similar to the placebo group or active comparator group. CONCLUSIONS: EMPA as add-on to MET was well tolerated and provided additional benefits beyond glucose lowering, such as weight loss and blood pressure reduction. However, high-quality trials with large samples are still needed in order to confirm their long-term safety.

MiR-10a* up-regulates coxsackievirus B3 biosynthesis by targeting the 3D-coding sequence.

MicroRNAs (miRNAs) are small non-coding RNAs that can posttranscriptionally regulate gene expression by targeting messenger RNAs. During miRNA biogenesis, the star strand (miRNA*) is generally degraded to a low level in the cells. However, certain miRNA* express abundantly and can be recruited into the silencing complex to regulate gene expression. Most miRNAs function as suppressive regulators on gene expression. Group B coxsackieviruses (CVB) are the major pathogens of human viral myocarditis and dilated cardiomyopathy. CVB genome is a positive-sense, single-stranded RNA. Our previous study shows that miR-342-5p can suppress CVB biogenesis by targeting its 2C-coding sequence. In this study, we found that the miR-10a duplex could significantly up-regulate the biosynthesis of CVB type 3 (CVB3). Further study showed that it was the miR-10a star strand (miR-10a*) that augmented CVB3 biosynthesis. Site-directed mutagenesis showed that the miR-10a* target was located in the nt6818-nt6941 sequence of the viral 3D-coding region. MiR-10a* was detectable in the cardiac tissues of suckling Balb/c mice, suggesting that miR-10a* may impact CVB3 replication during its cardiac infection. Taken together, these data for the first time show that miRNA* can positively modulate gene expression. MiR-10a* might be involved in the CVB3 cardiac pathogenesis.