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By directly altering microscopic interactions, pressure provides a powerful tuning knob for the exploration of condensed phases and geophysical phenomena1. The megabar regime represents an interesting frontier, in which recent discoveries include high-temperature superconductors, as well as structural and valence phase transitions2-6. However, at such high pressures, many conventional measurement techniques fail. Here we demonstrate the ability to perform local magnetometry inside a diamond anvil cell with sub-micron spatial resolution at megabar pressures. Our approach uses a shallow layer of nitrogen-vacancy colour centres implanted directly within the anvil7-9; crucially, we choose a crystal cut compatible with the intrinsic symmetries of the nitrogen-vacancy centre to enable functionality at megabar pressures. We apply our technique to characterize a recently discovered hydride superconductor, CeH9 (ref. 10). By performing simultaneous magnetometry and electrical transport measurements, we observe the dual signatures of superconductivity: diamagnetism characteristic of the Meissner effect and a sharp drop of the resistance to near zero. By locally mapping both the diamagnetic response and flux trapping, we directly image the geometry of superconducting regions, showing marked inhomogeneities at the micron scale. Our work brings quantum sensing to the megabar frontier and enables the closed-loop optimization of superhydride materials synthesis.

Miao Tang,1 Cong Zu,2 Anning He,2 Wenqian Wang,1 Bo Chen,1 Xinyu Zheng1,2 1Department of Breast Surgery, The First Hospital of China Medical University, 2Laboratory 1, Cancer Institute, China Medical University, Shenyang, People’s Republic of China Background: Suicide gene therapy in cancer can selectively kill tumors without damaging normal tissues. Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK), an original suicide kinase, makes use of the carcinomatous suicide gene therapy for broader substrate specificity and a higher catalytic rate.Methods: To enhance the anti-tumor efficacy of Dm-dNK and maintain its substrate specificity and safety control in the meantime, the conditionally replicative gene–viral system, ZD55–dNK (which contains the selective replication adenovirus, ZD55, encoded with Dm-dNK), was investigated in pushing a deeper development of this strategy. Selective replication, cell killing efficacy, and cytotoxicity, in combination with chemotherapy, were applied to two breast cell lines (MDA231 and MCF7 cells), two normal cell lines (WI38 and MRC5 cells), and the MCF7 xenograft model in vivo.Results: The preclinical study showed that ZD55–dNK, combined with 2',2'-difluorodeoxycytidine (DFDC), synergistically inhibited adenovirus replication in vitro but maintained specifically cancer cell killing efficacy. ZD55–dNK also greatly improved the antineoplastic effect in vitro and in breast cancer xenograft in vivo.Conclusion: The concomitant use of ZD55–dNK and DFDC is possibly a novel and promising approach to breast cancer treatment, and further investigation on the safe control of excessive virus replication and the efficacy of this approach in humans is warranted. Keywords: Dm-dNK, oncolytic adenovirus, cancer suicide gene therapy, nucleoside analogs, safety control

The most direct approach for characterizing the quantum dynamics of a strongly interacting system is to measure the time evolution of its full many-body state. Despite the conceptual simplicity of this approach, it quickly becomes intractable as the system size grows. An alternate approach is to think of the many-body dynamics as generating noise, which can be measured by the decoherence of a probe qubit. Here we investigate what the decoherence dynamics of such a probe tells us about the many-body system. In particular, we utilize optically addressable probe spins to experimentally characterize both static and dynamical properties of strongly interacting magnetic dipoles. Our experimental platform consists of two types of spin defects in nitrogen delta-doped diamond: nitrogen-vacancy colour centres, which we use as probe spins, and a many-body ensemble of substitutional nitrogen impurities. We demonstrate that the many-body system's dimensionality, dynamics and disorder are naturally encoded in the probe spins' decoherence profile. Furthermore, we obtain direct control over the spectral properties of the many-body system, with potential applications in quantum sensing and simulation.

Pressure alters the physical, chemical, and electronic properties of matter. The diamond anvil cell enables tabletop experiments to investigate a diverse landscape of high-pressure phenomena. Here, we introduce and use a nanoscale sensing platform that integrates nitrogen-vacancy (NV) color centers directly into the culet of diamond anvils. We demonstrate the versatility of this platform by performing diffraction-limited imaging of both stress fields and magnetism as a function of pressure and temperature. We quantify all normal and shear stress components and demonstrate vector magnetic field imaging, enabling measurement of the pressure-driven [Formula: see text] phase transition in iron and the complex pressure-temperature phase diagram of gadolinium. A complementary NV-sensing modality using noise spectroscopy enables the characterization of phase transitions even in the absence of static magnetic signatures.

Characterizing the local internal environment surrounding solid-state spin defects is crucial to harnessing them as nanoscale sensors of external fields. This is especially germane to the case of defect ensembles which can exhibit a complex interplay between interactions, internal fields, and lattice strain. Working with the nitrogen-vacancy (NV) center in diamond, we demonstrate that local electric fields dominate the magnetic resonance behavior of NV ensembles at a low magnetic field. We introduce a simple microscopic model that quantitatively captures the observed spectra for samples with NV concentrations spanning more than two orders of magnitude. Motivated by this understanding, we propose and implement a novel method for the nanoscale localization of individual charges within the diamond lattice; our approach relies upon the fact that the charge induces a NV dark state which depends on the electric field orientation.

Vaccines play essential roles in the fight against the COVID-19 pandemic. The development and assessment of COVID-19 vaccines have generally focused on the induction and boosting of neutralizing antibodies targeting the SARS-CoV-2 spike (S) protein. Due to rapid and continuous variation in the S protein, such vaccines need to be regularly updated to match newly emerged dominant variants. T-cell vaccines that target MHC I- or II-restricted epitopes in both structural and non-structural viral proteins have the potential to induce broadly cross-protective and long-lasting responses. In this work, the entire proteome encoded by SARS-CoV-2 (Wuhan-hu-1) is subjected to immunoinformatics-based prediction of HLA-A*02:01-restricted epitopes. The immunogenicity of the predicted epitopes is evaluated using peripheral blood mononuclear cells from convalescent Wuhan-hu-1-infected patients. Furthermore, predicted epitopes that are conserved across major SARS-CoV-2 lineages and variants are used to construct DNA vaccines expressing multi-epitope polypeptides. Most importantly, two DNA vaccine constructs induce epitope-specific CD8 + T-cell responses in a mouse model of HLA-A*02:01 restriction and protect immunized mice from challenge with Wuhan-hu-1 virus after hACE2 transduction. These data provide candidate T-cell epitopes useful for the development of T-cell vaccines against SARS-CoV-2 and demonstrate a strategy for quick T-cell vaccine candidate development applicable to other emerging pathogens.

Experimental realization of a universal set of quantum logic gates is the central requirement for the implementation of a quantum computer. In an 'all-geometric' approach to quantum computation (1,2), the quantum gates are implemented using Berry phases (3) and their non-Abelian extensions, holonomies (4), from geometric transformation of quantum states in the Hilbert space (5). Apart from its fundamental interest and rich mathematical structure, the geometric approach has some built-in noise-resilience features (1,2,6,7). On the experimental side, geometric phases and holonomies have been observed in thermal ensembles of liquid molecules using nuclear magnetic resonance (8,9); however, such systems are known to be non-scalable for the purposes of quantum computing (10). There are proposals to implement geometric quantum computation in scalable experimental platforms such as trapped ions (11), superconducting quantum bits (12) and quantum dots (13), and a recent experiment has realized geometric single-bit gates in a superconducting system (14). Here we report the experimental realization of a universal set of geometric quantum gates using the solid-state spins of diamond nitrogen-vacancy centres. These diamond defects provide a scalable experimental platform (15-17) with the potential for room-temperature quantum computing (16-19), which has attracted strong interest in recent years (20). Our experiment shows that all-geometric and potentially robust quantum computation can be realized with solid-state spin quantum bits, making use of recent advances in the coherent control of this system (15-20)., Under adiabatic cyclic evolution, a non-degenerate eigenstate of a quantum system acquires a phase factor, which has a dynamical component proportional to the time integral of the eigenstate energy and [...]

Background The association between dietary thiamine intake and the risk of diabetes remains unknown. Aim We aimed to evaluate the relation of dietary thiamine intake with new-onset diabetes and examine possible effect modifiers. Design Prospective cohort study. Methods A total of 16 272 participants who were free of diabetes at baseline were enrolled from China Health and Nutrition Survey (CHNS). Dietary nutrients intake information was collected by 3-day dietary recalls in addition to using a 3-day food-weighed method to assess cooking oil and condiment consumption. New-onset diabetes was defined as a fasting blood glucose ≥7.0 mmol/l or a glycated haemoglobin (HbA1c) ≥6.5% (48 mmol/mol) or diagnosed by a physician during the follow-up. Results During a median follow-up duration of 9.0 years, new-onset diabetes occurred in 1101 participants. Overall, the association between dietary thiamine intake and new-onset diabetes followed a U-shape (P for non-linearity <0.001). Consistently, when thiamine intake was assessed as quartiles, compared with those in the 2–3 quartiles (0.75 to 1.10 mg/day), the significantly higher risks of new-onset diabetes were found in participants in the first quartile [adjusted hazard ratio (HR), 1.33; 95% confidence interval (CI): 1.10, 1.61] and the fourth quartile (adjusted HR, 1.39; 95% CI: 1.17, 1.67). Similar results were found when further adjusting for the intake of other major nutrients or food groups; or using the propensity score weighting to control the imbalance of covariates. Conclusion Our results suggested that there was a U-shape association between dietary thiamine intake and new-onset diabetes in general Chinese adults, with a minimal risk at 0.75–1.10 mg/day. [ABSTRACT FROM AUTHOR]

Straw return and biochar are often applied to improve soil fertility and increase crop yield. However, the effects of these practices on soil aggregates and tobacco leaf yield and quality are still unclear. Five treatments: no straw (CK), application of rice straw (RS), tobacco straw biochar (TSB), RS plus TSB (RS+TSB), and RS plus pig manure (RS+PM) were conducted to evaluate the effects of straw return and biochar on soil aggregates, tobacco leaf yield and quality in Southern Anhui, China. Results showed that TSB significantly increased soil pH by 0.38. The RS+TSB and RS+PM significantly increased the contents of soil organic matter, available nitrogen (N) and potassium (K). Biochar and straw return increased >5 mm aggregates fraction in topsoil (0-20 cm) with an order of RS+PM > RS+TSB > TSB > RS. The RS+TSB and RS+PM significantly increased the yield, appearance and sensory quality of tobacco leaf. The leaf yield and quality were positively correlated with >5 mm aggregates fraction, but negatively correlated with <0.25 mm aggregates. These results indicated that straw return with pig manure (375 kg ha−1 ) or biochar (1050 kg ha−1 ) increased the yield and quality of tobacco leaf, likely due to their effect on large soil aggregate and the available of macronutrients in soil. [ABSTRACT FROM AUTHOR]

Polyaniline (PANI) has long been explored as a promising organic cathode for Li-ion batteries. However, its poor electrochemical utilization and cycling instability cast doubt on its potential for practical applications. In this work, we revisit the electrochemical performance of PANI in nonaqueous electrolytes, and reveal an unprecedented reversible capacity of 197.2 mAh g−1 (244.8 F g−1) when cycled in a wide potential range of 1.5 to 4.4 V vs. Li+/Li. This ultra-high capacity derives from 70% -NH- transformed to =NH+- during deep charging/discharging process. This material also demonstrates a high average coulombic efficiency of 98%, an excellent rate performance with 73.5 mAh g−1 at 1800 mA g−1, and retains 76% of initial value after 100 cycles, which are among the best reported values for PANI electrodes in battery applications.

AZO/Ag/AZO transparent conductive films were prepared on PMMA substrate by DC magnetron sputtering at low temperature (70 ℃). The effect of AZO sputtering power on the structure and properties of AZO/Ag/AZO thin films were investigated. In order to encapsulate AZO/Ag/AZO films, the films were laminated with another uncoated PMMA substrate and polyurethane film. Damp and heat resistance and heating performance of this laminated structure were discussed. The morphology and structure of the films were characterized by SEM, XRD and AFM. The results show that the sputtering power of AZO affects the surface energy of AZO layer and the crystallization of AZO/Ag/AZO films. The AZO/Ag/AZO films which prepared with AZO sputtering power of 100W and 150W exhibit the best performance with a low sheet resistance of 3.7 Ω/sq and a high transmittance of 86.1% at room temperature. The optical and electrical properties of PMMA laminated structure remain stable after 30 days of damp-heat experiment. The temperature-time curve during the heating process of the PMMA laminated structure at room temperature shows fast temperature response time and good temperature uniformity under 5 V DC voltage. The PMMA laminated structure exhibits saturation temperature stability in cold convection air (−10-−40 ℃).

Liming is a common practice for improving plant growth and yield on acidic soils. However, knowledge is still limited on the effect of liming on tobacco growth and leaf quality planted on acidic soil. In this study, effects of lime (Ca(OH)2) (0, 0.75, 1.5 and 3 t ha-1) on soil nutrient status (Ca2+ and Mg2+ in particular), growth, nutrient accumulation and quality of flue-cured tobacco was investigated in an acidic soil located in Anhui province, China. The results showed that liming significantly increased soil pH both 30 days after transplanting and after the harvest of the tobacco. In comparison with CK (no lime application), liming at a rate of 1.5 t ha-1 increased leaf number and leaf dry weight by 15% and 11%, and enhanced the appearance and smoking quality of cured leaves by 7% and 9%, respectively. Moreover, liming significantly increased calcium concentration, while decreased nitrogen and magnesium concentration in the cured leaves. The increase in cured leaf quality was attributed to the improvement of chemical composition, particularly the increase in reducing sugar content. Together, our results suggest that Ca(OH)2 application at a rate of 1.5 t ha-1 may alleviate soil acidification and improve yield and quality of flue-cured tobacco in Anhui province, China. [ABSTRACT FROM AUTHOR]

The vibration and noise that resulted from turbomachinery, such as fans, compressors, and centrifugal pumps, are known to bring considerable disturbance and pollution to the machine itself, the environment, and the operators. Hence, how to cope with the vibration and noise has become a recent research focus. With the advancement of materials science, more and more new nanomaterials have been applied in the field of noise and vibration reduction. To be specific, carbon-based nanomaterials, such as carbon fibers, carbon nanotubes, and graphenes, have achieved outstanding results. Carbon nanocomposites, such as carbon nanofibers, carbon nanotubes, and graphenes, are characterized by their low densities, high strengths, and high elastic moduli, all of which made carbon nanocomposites the most promising vibration and noise-reduction composites, thanks to their damping properties, compatibilities, noise and vibration absorption qualities, and wide wave-absorbing frequency bands. In light of this, this paper summarizes the progresses and application prospects of such carbon nanocomposites as carbon nanofibers, carbon nanotubes, and graphenes in the field of turbomachinery vibration and noise reduction.

We report the first experimental demonstration of distillation of quantum nonlocality, confirming the recent theoretical protocol [ Phys. Rev. Lett. 102 120401 (2009)]. Quantum nonlocality is described by a correlation box with binary inputs and outputs, and the nonlocal boxes are realized through appropriate measurements on polarization entangled photon pairs. We demonstrate that nonlocality is amplified by connecting two nonlocal boxes into a composite one through local operations and four-photon measurements. [ABSTRACT FROM AUTHOR]

We report the first state-independent experimental test of quantum contextuality on a single photonic qutrit (three-dimensional system), based on a recent theoretical proposal [Phys. Rev. Lett. 108, 030402 (2012)]. Our experiment spotlights quantum contextuality in its most basic form, in a way that is independent of either the state or the tensor product structure of the system. [ABSTRACT FROM AUTHOR]

We propose and experimentally demonstrate a zero-sum game that is in a fair Nash equilibrium for classical players, but has the property that a quantum player can always win using an appropriate strategy. The gain of the quantum player is measured experimentally for different quantum strategies and input states. It is found that the quantum gain is maximized by a maximally entangled state, but does not decrease to zero when entanglement disappears. Instead, it links with another kind of quantum correlation described by discord for the qubit case and the connection is demonstrated both theoretically and experimentally. [ABSTRACT FROM AUTHOR]

Background: Pyroptosis is the term for caspase-1-dependent cell death associated with pro-inflammatory cytokines. The role of alveolar macrophage (AM) pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains unclear. Methods: C57BL/6 wild-type mice were assigned to sham, lipopolysaccharide (LPS) + vehicle, LPS + acetyl-tyrosyl-valyl- alanyl-aspartyl-chloromethylketone (Ac-YVAD-CMK) and LPS + Z-Asp-Glu-Val-Asp-fluoromethylketone groups. Mice were given intraperitoneal (IP) injections of LPS. Drugs were IP injected 1 h before LPS administration. Mice were sacrificed 16 h after LPS administration, and AMs were isolated. Western blot analysis for active caspase-1 and cleaved caspase-3, evaluation of lung injury and a cytokine release analysis were performed. AMs were treated with LPS and adenosine triphosphate (ATP); caspase-1-dependent cell death was evaluated using flow cytometry; the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) pyroptosomes were examined by immunofluorescence. Results: The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group. In the ex vivo study, the caspase-1/propidium iodide-positive cells, caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation. The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death. Ac-YVAD-CMK also reduced the lung injury, pulmonary edema and total protein in bronchoalveolar lavage fluid (BALF). In addition, Ac-YVAD-CMK significantly inhibited interleukin-α2 (IL-1α2) release both in serum and BALF and reduced the levels of IL-18, tumor necrosis factor-α± (TNF-α±), High Mobility Group Box 1 (HMGB1) in BALF during LPS-induced ALI/ARDS. Conclusions: This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury. These preliminary findings may form the basis for further studies to evaluate this pathway as a target for prevention or reduction of ALI/ARDS.

We experimentally demonstrate a robust dynamical decoupling protocol with bounded controls using long soft pulses, eliminating a challenging requirement of strong control pulses in conventional implementations. This protocol is accomplished by designing the decoupling propagators to go through a Eulerian cycle of the coupler group [Phys. Rev. Lett. 90, 037901 (2003)]. We demonstrate that this Eulerian decoupling scheme increases the coherence time by two orders of magnitude in our experiment under either dephasing or a universal noise environment. [ABSTRACT FROM AUTHOR]

Abstract Background As a known regulator of apoptosis, survivin has positive relationship with lymphatic metastasis in breast cancer. This study aims to detect the difference in expression between survivin and vascular endothelial growth factor-C (VEGF-C) in treated breast cancer cells and tissues, and to analyze the correlation among survivin, VEGF-C and lymphatic metastasis. Methods Plasmid with survivin and VEGF-C shRNA and lentivirus with survivin gene were constructed and transfected into breast cancer cell ZR-75-30. Then the expressions of the two genes were examined using western blot analysis and real-time PCR. The change of invasiveness of breast cancer cells was assessed using matrigel invasion assay. Using immunohistochemistry, the expression of survivin and VEGF-C were analyzed in 108 clinical breast cancer cases with breast cancer tissue and lymph node. Results Survivin regulated the expression of VEGF-C at both protein and mRNA levels in breast cancer cells. Immunohistochemical analysis showed that the level of VEGF-C expression was significantly related with that of survivin in breast cancer tissues (pp Conclusions Survivin takes an important part in regulating the expression of VEGF-C. VEGF-C could influence the invasive ability mediated by survivin. The co-expression of survivin and VEGF-C is more statistically significant to assess lymphatic metastasis in breast cancer. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9193530897100952

The router is a key element for a network. We describe a scheme to realize genuine quantum routing of single-photon pulses based on cascading of conditional quantum gates in a Mach-Zehnder interferometer and report a proof-of-principle experiment for its demonstration using linear optics quantum gates. The polarization of the control photon routes in a coherent way the path of the signal photon while preserving the qubit state of the signal photon represented by its polarization. We demonstrate quantum nature of this router by showing entanglement generated between the initially unentangled control and signal photons, and confirm that the qubit state of the signal photon is well preserved by the router through quantum process tomography. [ABSTRACT FROM AUTHOR]

As a way to circumvent the quantum no-cloning theorem, approximate quantum cloning protocols have received wide attention with remarkable applications. Copying of quantum states to memory qubits provides an important strategy for eavesdropping in quantum cryptography. We report an experiment that realizes cloning of quantum states from an electron spin to a nuclear spin in a hybrid solid-state spin register with near-optimal fidelity. The nuclear spin provides an ideal memory qubit at room temperature, which stores the cloned quantum states for a millisecond under ambient conditions, exceeding the lifetime of the original quantum state carried by the electron spin by orders of magnitude. The realization of a cloning machine with built-in quantum memory provides a key step for application of quantum cloning in quantum information science. [ABSTRACT FROM AUTHOR]

The article offers the author's insights on the comment by E. Amselem and colleagues on experimental test of quantum contextuality in an indivisible system which misinterprets the assumption and logic of their experiment. The author says that they assumed the functioning of simple linear optical devices such as polarization beam splitters. He mentions that they assumed that half wave plates (HWP), which were set at an angle θ have tranform the polarization H, V of the incoming light field.

Objectives: To describe the time course and characteristics of an insecticide-associated incident and highlight potential risks from similar outbreaks that may occur in other areas to enhance the preparedness of emergency physicians and other healthcare providers to deal with the sequelae of these events. Study design: Outbreak investigation Methods: From 5 to 8 August 2008, an outbreak investigation was carried out among the affected primary school located in the refugee camp area of Lixian district, Sichuan, China. Affected pupils, parents, teachers and doctors working in the local medical stations were visited. Clinical checking, clinical treatment, epidemiological investigation and environmental investigation were undertaken. Results: In total, 138 individuals were diagnosed with acute conjunctivitis, characterized by inflammation of the conjunctiva and intense ocular symptoms such as redness, itching and mucus discharge. According to the results, all risk factors (i.e. drinking water, indoor air and the materials used in camp classrooms) were excluded except insecticide exposure. The characteristics of symptoms, distribution of cases and records of irregular insecticide spraying support the assumption that the conjunctivitis outbreak was associated with synthetic pyrethroid alphacyperm ethrin exposure. Conclusion: The results suggest that non-standard operating procedures in pest control could lead to disease incidents. Medical rescue teams should receive training and education in preventive techniques. [ABSTRACT FROM AUTHOR]

We experimentally demonstrate room-temperature storage of quantum entanglement using two nuclear spins weakly coupled to the electronic spin carried by a single nitrogen-vacancy center in diamond. We realize universal quantum gate control over the three-qubit spin system and produce entangled states in the decoherence-free subspace of the two nuclear spins. By injecting arbitrary collective noise, we demonstrate that the decoherence-free entangled state has coherence time longer than that of other entangled states by an order of magnitude in our experiment. [ABSTRACT FROM AUTHOR]

Aims: To assess the relationship of longitudinal changes in fat mass (FM), lean mass (LM) and waist circumference (WC) with incident kidney outcomes in people with overweight/obesity and type 2 diabetes mellitus (T2DM)., Materials and Methods: A total of 3927 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 from the Look AHEAD (Action for Health in Diabetes) trial were included. The primary outcome was kidney outcomes, defined as a decrease in eGFR of at least 40% from baseline at follow-up visit, or end-stage kidney disease., Results: During a median follow-up of 8.0 years, 450 kidney outcomes were documented after the first 1 year. In the intensive lifestyle intervention (ILI) group, reductions in FM (per 10% decrease, adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69-0.94) and WC (per 10% decrease, adjusted HR 0.72, 95% CI 0.59-0.88) from baseline to 1-year follow-up were significantly associated with a lower risk of kidney outcomes. The change in LM was not significantly associated with risk of kidney outcomes (per 10% decrease, adjusted HR 0.78, 95% CI 0.58-1.06). In the diabetes support and education group (control group), no significant association was found between changes in body composition and kidney outcomes. Similar results were observed for the 4-year changes in body composition., Conclusions: In this post hoc analysis of the Look AHEAD trial, longitudinal declines in FM and WC were associated with a lower risk of kidney outcomes in the ILI group in participants with overweight/obesity and T2DM., (© 2024 John Wiley & Sons Ltd.)

Levitated diamond particles in high vacuum with internal spin qubits have been proposed for exploring macroscopic quantum mechanics, quantum gravity, and precision measurements. The coupling between spins and particle rotation can be utilized to study quantum geometric phase, create gyroscopes and rotational matter-wave interferometers. However, previous efforts in levitated diamonds struggled with vacuum level or spin state readouts. To address these gaps, we fabricate an integrated surface ion trap with multiple stabilization electrodes. This facilitates on-chip levitation and, for the first time, optically detected magnetic resonance measurements of a nanodiamond levitated in high vacuum. The internal temperature of our levitated nanodiamond remains moderate at pressures below 10 -5 Torr. We have driven a nanodiamond to rotate up to 20 MHz (1.2 × 10 9 rpm), surpassing typical nitrogen-vacancy (NV) center electron spin dephasing rates. Using these NV spins, we observe the effect of the Berry phase arising from particle rotation. In addition, we demonstrate quantum control of spins in a rotating nanodiamond. These results mark an important development in interfacing mechanical rotation with spin qubits, expanding our capacity to study quantum phenomena., (© 2024. The Author(s).)

Straw and biochar, two commonly used soil amendments, have been shown to enhance soil fertility and the composition of microbial communities. To compare the effects of straw and biochar on soil fertility, particularly focusing on soil dissolved organic matter (DOM) components, and the physiochemical properties of soil and microbial communities, a combination of high-throughput sequencing and three-dimensional fluorescence mapping technology was employed. In our study, we set up four treatments, i.e., without biochar and straw (B0S0); biochar only (B1S0); straw returning only (B0S1); and biochar and straw (B1S1). Our results demonstrate that soil organic matter (SOM), available nitrogen (AN), and available potassium (AK) were increased by 34.71%, 22.96%, and 61.68%, respectively, under the B1S1 treatment compared to the B0S0 treatment. In addition, microbial carbon (MBC), dissolved organic carbon (DOC), and particulate organic carbon (POC) were significantly increased with the B1S1 treatment, by 55.13%, 15.59%, and 125.46%, respectively. The results also show an enhancement in microbial diversity, the composition of microbial communities, and the degree of soil humification with the application of biochar and straw. Moreover, by comparing the differences in soil fertility, DOM components, and other indicators under different treatments, the combined treatments of biochar and straw had a more significant positive impact on paddy soil fertility compared to biochar. In conclusion, our study revealed the combination of straw incorporation and biochar application has significant impacts and is considered an effective approach to improving soil fertility.

Background: The association between the TDRD6 variants and human infertility remains unclear, as only one homozygous missense variant of TDRD6 was found to be associated with oligoasthenoteratozoospermia (OAT)., Methods: Whole-exome sequencing and Sanger sequencing were employed to identify potential pathogenic variants of TDRD6 in infertile men. Histology, immunofluorescence, immunoblotting and ultrastructural analyses were conducted to clarify the structural and functional abnormalities of sperm in mutated patients. Tdrd6 -knockout mice were generated using the CRISPR-Cas9 system. Total RNA-seq and single-cell RNA-seq (scRNA-seq) analyses were used to elucidate the underlying molecular mechanisms, followed by validation through quantitative RT-PCR and immunostaining. Intracytoplasmic sperm injection (ICSI) was also used to assess the efficacy of clinical treatment., Results: Bi-allelic TDRD6 variants were identified in five unrelated Chinese individuals with OAT, including homozygous loss-of-function variants in two consanguineous families. Notably, besides reduced concentrations and impaired motility, a significant occurrence of acrosomal hypoplasia was detected in multiple spermatozoa among five patients. Using the Tdrd6 -deficient mice, we further elucidate the pivotal role of TDRD6 in spermiogenesis and acrosome identified. In addition, the mislocalisation of crucial chromatoid body components DDX4 (MVH) and UPF1 was also observed in round spermatids from patients harbouring TDRD6 variants. ScRNA-seq analysis of germ cells from a patient with TDRD6 variants revealed that TDRD6 regulates mRNA metabolism processes involved in spermatid differentiation and cytoplasmic translation., Conclusion: Our findings strongly suggest that TDRD6 plays a conserved role in spermiogenesis and confirms the causal relationship between TDRD6 variants and human OAT. Additionally, this study highlights the unfavourable ICSI outcomes in individuals with bi-allelic TDRD6 variants, providing insights for potential clinical treatment strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study aimed to explore the knowledge and attitude (KA) toward postoperative antithrombotic management and prevention among coronary artery disease (CAD) patients who underwent coronary revascularization., Methods: This cross-sectional study enrolled CAD outpatients and inpatients between May and December 2023 at Kailuan Medical Group at Tangshan. Basic demographic characteristics and KA scores were collected through a self-made questionnaire., Results: This study included 523 valid questionnaires. The mean knowledge and attitude scores were 13.20 ± 6.20 (range: 0-26) and 43.68 ± 6.01 (range: 21-50), respectively, indicating poor knowledge and favorable attitude. Multivariable logistic regression analysis showed that junior high school education (OR = 2.160, P  = 0.035), high school or technical school education (OR = 2.356, P  = 0.039), and monthly average income >5,000 RMB (OR = 3.407, P  = 0.002) were independently associated with knowledge. Knowledge (OR = 1.095, P  = 0.002), BMI ≥ 24.0 kg/m 2 (OR = 0.372, P  = 0.011), junior high school (OR = 3.699, P  = 0.002), high school or technical school (OR = 2.903, P  = 0.028), high associate degree or above education (OR = 6.068, P  = 0.014), monthly average income 3,000-5,000 RMB (OR = 0.296, P  = 0.005), monthly average income > 5,000 RMB (OR = 0.225, P  = 0.021), with hypertension (OR = 0.333, P  = 0.003), blood tests every 2-3 weeks (OR = 10.811, P  = 0.011), blood tests every month (OR = 4.221, P  = 0.024), and blood tests every 2-3 months (OR = 3.342, P  = 0.033) were independently associated with attitude., Conclusion: CAD patients who underwent coronary revascularization had poor knowledge but favorable attitudes toward postoperative antithrombotic management and prevention. The study underscores the need for targeted education, especially for individuals with lower education and income levels, ultimately improving patient compliance and cardiovascular outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Liu, Zhang, Yang, Chen, Zu, Wang, Dai and Zhao.)

The human population will be approximately 9.7 billion by 2050, and food security has been identified as one of the key issues facing the global population. Agrochemicals are an important tool available to farmers that enable high crop yields and continued access to healthy foods, but the average new agrochemical active ingredient takes more than ten years, 350 million dollars, and 20,000 animals to develop and register. The time, monetary, and animal costs incentivize the use of New Approach Methodologies (NAMs) in early-stage screening to prioritize chemical candidates. This review outlines NAMs that are currently available or can be adapted for use in early-stage screening agrochemical programs. It covers new in vitro screens that are on the horizon in key areas of regulatory concern. Overall, early-stage screening with NAMs enables the prioritization of development for agrochemicals without human and environmental health concerns through a more directed, agile, and iterative development program before animal-based regulatory testing is even considered.

Soil amendment is an important strategy for improving soil quality and crop yield. From 2014 to 2019, we conducted a study to investigate the effects of tobacco straw return with lime on soil nutrients, soil microbial community structure, tobacco leaf yield, and quality in southern Anhui, China. A field experiment was conducted with four treatments: straw removed (CK), straw return (St), straw return with dolomite (St + D), and straw return with lime (St + L). Results showed that after 5 years of application, the St + L significantly increased the soil pH by 16.9%, and the contents of soil alkaline nitrogen (N) and available potassium (K) by 17.2% and 23.0%, respectively, compared with the CK. Moreover, the St + L significantly increased tobacco leaf yield (24.0%) and the appearance (9.1%) and sensory (5.9%) quality of flue-cured tobacco leaves. The addition of soil conditioners (straw, dolomite, and lime) increased both the total reads and effective sequences of soil microorganisms. Bacterial diversity was more sensitive to changes in the external environment compared to soil fungi. The application of soil amendments (lime and straw) promoted the growth of beneficial microorganisms in the soil. Additionally, bacterial species had greater competition and limited availability of resources for survival compared to fungi. The results showed that soil microorganisms were significantly influenced by the presence of AK, AN, and pH contents. These findings can provide an effective method for improving the quality of flue-cured tobacco leaves and guiding the amelioration of acidic soil in regions where tobacco-rice rotation is practiced., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear., Methods: We tested a novel "all-in-one" strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored., Results: After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease-negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100)., Conclusions: Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.)., (Copyright © 2024 Massachusetts Medical Society.)

Introduction: Porcine viral diarrhea is a common clinical disease, which results in high mortality and economic losses in the pig industry. Porcine epidemic diarrhea virus (PEDV), porcine rotavirus (PoRV), and porcine deltacoronavirus (PDCoV) are important diarrhea viruses in pig herds. The similarities of their clinical symptoms and pathological changes make it difficult to distinguish these three viruses clinically. Therefore, there is a need for a highly sensitive and specific method to simultaneously detect and differentiate these viruses., Methods: A multiplex real-time PCR assay using TaqMan probes was developed to simultaneously detect PEDV, PoRV, and PDCoV. To assess the efficacy of the established assay, 30 clinical samples with diarrhea symptoms were used to compare the results obtained from the multiplex real-time PCR assay with those obtained from commercial singleplex real-time PCR kit. Importantly, a total of 4,800 diarrhea samples were tested and analyzed to validate the utility of the assay., Results: This multiplex real-time PCR assay showed high sensitivity, specificity, and excellent repeatability with a detection limit of 1 × 10 2 copies/μL. Comparing the results of the commercial singleplex real-time PCR kit and the multiplex real-time PCR method for detecting PEDV, PoRV, and PDCoV, there was complete agreement between the two approaches. Clinical data revealed single infection rates of 6.56% for PEDV, 21.69% for PoRV, and 6.65% for PDCoV. The co-infection rates were 11.83% for PEDV + PoRV, 0.29% for PEDV + PDCoV, 5.71% for PoRV + PDCoV, and 1.29% for PEDV + PDCoV + PoRV, respectively., Discussion: The multiplex real-time PCR method established in this study is a valuable diagnostic tool for simultaneously differentiating PEDV, PoRV, and PDCoV. This method is expected to significantly contribute to prevent and control the spread of infectious diseases, as well as aid in conducting epidemiological investigations., Competing Interests: CZ, YL, and XL were employed by Shandong New Hope Liuhe Agriculture and Animal Husbandry Technology Co., Ltd. (NHLH Academy of Swine Research). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ren, Zu, Li, Li, Gu, Chen and Li.)

Objective: We assessed the relationship of body weight time in target range (TTR) with composite kidney outcome in people with overweight/obesity and type 2 diabetes mellitus (T2DM)., Research Design and Methods: Included in this study were 3,601 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 from the Look AHEAD (Action for Health in Diabetes) trial. Body weight TTR was defined as the proportion of time during the first 4 years that body weight was within the weight loss target (a weight loss of ≥7% from baseline). The primary outcome was composite kidney outcome, defined as eGFR decline ≥30% from baseline and to a level <60 mL/min/1.73 m2 at follow-up visit, or end-stage kidney disease., Results: During a median follow-up of 8.0 years, 435 cases of composite kidney outcome were documented. Body weight TTR during the first 4 years was inversely associated with the subsequent risk of composite kidney outcome (per SD increment; adjusted hazard ratio [HR] 0.81; 95% CI 0.70-0.93). Accordingly, the adjusted HRs (95% CI) of composite kidney outcome were 1.00 (reference), 0.73 (0.54-1.00), 0.71 (0.52-0.99), and 0.54 (0.36-0.80) for participants with body weight TTR of 0%, >0% to <29.9%, 29.9% to <69.7%, and 69.7% to <100%, respectively. Similar results were found for a doubling of the urine albumin to creatinine ratio (secondary outcome)., Conclusions: A higher body weight TTR, with a weight loss target of losing ≥7% of initial weight, was associated with a lower risk of kidney outcomes in participants with overweight/obesity and T2DM., (© 2024 by the American Diabetes Association.)

Background and Objective: The prospective association between dietary zinc (Zn) intake and cognitive decline remains uncertain. We aimed to assess the relationship of dietary Zn intake with the risk of cognitive decline in the Chinese older people, and examine the possible effect modifiers on this association., Methods: A total of 3,106 older Chinese adults aged 55 years or older from China Health and Nutrition Survey were included. Dietary nutrients intake information was collected by combined 24-h dietary recalls with weighing food inventory. The cognitive decline was defined as the 5-year decline rate in global and composite cognitive scores, based on a subset of items from the Telephone Interview for Cognitive Status-modified., Results: The median follow-up duration was 5.9 years. There was an L-shaped association between dietary Zn intake and the 5-year decline rates in global and composite cognitive scores, with an inflection point at 8.8 mg/day of dietary Zn. For the composite cognitive scores, compared with the first quantile (<7.9 mg/day) of dietary Zn intake, quantiles 2-6 (≥7.9 mg/day) had a significantly slower cognitive decline rate (β: -0.24; 95% confidence interval: -0.40 to -0.07). Similar results were found for the global cognitive scores. Moreover, the inverse association between dietary Zn intake and cognitive decline in composite cognitive scores was significantly stronger in those with lower levels of physical activity (P-interactions = 0.041)., Conclusion: Dietary Zn intake was negatively associated with cognitive decline in the older people. Maintaining appropriate dietary Zn levels may prevent cognitive decline., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Spin defects in van der Waals materials offer a promising platform for advancing quantum technologies. Here, we propose and demonstrate a powerful technique based on isotope engineering of host materials to significantly enhance the coherence properties of embedded spin defects. Focusing on the recently-discovered negatively charged boron vacancy center ([Formula: see text]) in hexagonal boron nitride (hBN), we grow isotopically purified h 10 B 15 N crystals. Compared to [Formula: see text] in hBN with the natural distribution of isotopes, we observe substantially narrower and less crowded [Formula: see text] spin transitions as well as extended coherence time T 2 and relaxation time T 1 . For quantum sensing, [Formula: see text] centers in our h 10 B 15 N samples exhibit a factor of 4 (2) enhancement in DC (AC) magnetic field sensitivity. For additional quantum resources, the individual addressability of the [Formula: see text] hyperfine levels enables the dynamical polarization and coherent control of the three nearest-neighbor 15 N nuclear spins. Our results demonstrate the power of isotope engineering for enhancing the properties of quantum spin defects in hBN, and can be readily extended to improving spin qubits in a broad family of van der Waals materials., (© 2024. The Author(s).)

Positron emission tomography (PET) scans can reveal abnormal metabolic activities of cells and provide favorable information for clinical patient diagnosis. Generally, standard-dose PET (SPET) images contain more diagnostic information than low-dose PET (LPET) images but higher-dose scans can also bring higher potential radiation risks. To reduce the radiation risk while acquiring high-quality PET images, in this paper, we propose a 3D multi-modality edge-aware Transformer-GAN for high-quality SPET reconstruction using the corresponding LPET images and T1 acquisitions from magnetic resonance imaging (T1-MRI). Specifically, to fully excavate the metabolic distributions in LPET and anatomical structural information in T1-MRI, we first use two separate CNN-based encoders to extract local spatial features from the two modalities, respectively, and design a multimodal feature integration module to effectively integrate the two kinds of features given the diverse contributions of features at different locations. Then, as CNNs can describe local spatial information well but have difficulty in modeling long-range dependencies in images, we further apply a Transformer-based encoder to extract global semantic information in the input images and use a CNN decoder to transform the encoded features into SPET images. Finally, a patch-based discriminator is applied to ensure the similarity of patch-wise data distribution between the reconstructed and real images. Considering the importance of edge information in anatomical structures for clinical disease diagnosis, besides voxel-level estimation error and adversarial loss, we also introduce an edge-aware loss to retain more edge detail information in the reconstructed SPET images. Experiments on the phantom dataset and clinical dataset validate that our proposed method can effectively reconstruct high-quality SPET images and outperform current state-of-the-art methods in terms of qualitative and quantitative metrics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background & Aims: This study aims to assess the nutritional status of patients during the different phases of the Chimeric Antigen Receptor (CAR)-T cell therapy and to identify prominent risk factors of hypoalbuminemia in patients after CAR-T treatment. The clinical consequences of malnutrition in cancer patients have been highlighted by growing evidence from previous clinical studies. Given CAR-T cell therapy's treatment intensity and possible side effects, it is important to provide patients with sufficient medical attention and support for their nutritional well-being., Methods: This study was conducted from May 2021 to December 2021 among patients undergoing CAR-T cell therapy at the Bone Marrow Transplantation Center in The First Affiliated Hospital of Zhejiang University School of Medicine. Logistic regression analysis was performed to investigate the risk factors associated with hypoalbuminemia. Participants were divided into the cytokine release syndrome (CRS) group (n = 60) and the non-CRS group (n = 11) to further analyze the relationship between hypoalbuminemia and CRS., Results: CRS (OR = 13.618; 95% CI = 1.499-123.709; P = 0.013) and baseline albumin (ALB) (OR = 0.854; 95% CI = 0.754-0.967; P = 0.020) were identified as the independent clinical factors associated with post-CAR-T hypoalbuminemia. According to the nadir of serum albumin, hypoalbuminemia occurred most frequently in patients with severe CRS (78.57%). The nadir of serum albumin (r =  - 0.587, P < 0.001) and serum albumin at discharge (r =  - 0.315, P = 0.01) were negatively correlated for the duration of CRS. Furthermore, patients with hypoalbuminemia deserved longer hospitalization (P = 0.04)., Conclusions: CRS was identified as a significant risk factor associated with post-CAR-T hypoalbuminemia. An obvious decline in serum albumin was observed as the grade and duration of CRS increase. However, further research is still needed to elucidate the mechanisms of CRS-associated hypoalbuminemia., (© 2023. The Author(s).)

Background Aims: With the increasing application of chimeric antigen receptor (CAR)-T cell therapy in various malignancies, an extra toxicity profile has been revealed, including a severe complication resembling hemophagocytic lymphohistiocytosis (HLH), which is usually disguised by severe cytokine release syndrome (CRS)., Methods: In a clinical trial in whom 99 patients received B-cell maturation antigen CAR-T cells, we identified 20 (20.20%) cases of CAR-T cell-associated HLH (carHLH), most of whom possessed a background of severe CRS (grade ≥3). The overlapping features of carHLH and severe CRS attracted us to further explore the differences between them., Results: We showed that carHLH can be distinguished by extreme elevation of interferon-γ, granzyme B, interleukin-1RA and interleukin-10, which can be informative in developing prevention and management strategies of this toxicity. Moreover, we developed a predictive model of carHLH with a mean area under the curve of 0.81 ± 0.07, incorporating serum lactate dehydrogenase at day 6 post-CRS and serum fibrinogen at day 3 post-CRS., Conclusions: The incidence of carHLH in CAR-T recipients might be relatively higher than we previously thought. relatively higher than we previously. A cytokine network distinguished from CRS is responsible for carHLH. And corresponding cytokine-directed therapies, especially targeting IL-10, are worth trying., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: The association between dietary copper (Cu) intake and cognitive decline remains uncertain. We aim to investigate the longitudinal association of dietary Cu with cognitive decline in Chinese elderly., Methods: A total of 3,106 Chinese adults aged older than or equal to 55 years from China Health and Nutrition Survey (CHNS) were included. Dietary nutrients information was collected by 24-hours dietary recalls in combination with a food-weighted method. The 5-year change rates in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status-modified (TICS-m) was calculated as the last-survey score minus the baseline score, then divided by the follow-up time (unit, years) and multiplied by five., Results: The median follow-up duration was 5.9 years. There was a nonlinear association of dietary Cu intake with the 5-year change rates in global or composite cognitive scores, with the inflection point at approximately 1.3 mg/day of dietary Cu intake. Accordingly, for the composite cognitive score, compared to the first quantile (<1.28 mg/day), those with dietary Cu in quantiles 2-8 (≥1.28 mg/day) had a significantly slower cognitive decline rate (B, 0.30; 95% CI, 0.13, 0.47). Similar results were found for the global cognitive score. Moreover, the inverse association between dietary Cu and cognitive decline was stronger in those with lower dietary fat intake and lower levels of physical activity (All p-interactions <0.05)., Conclusion: There was a nonlinear inverse association of dietary Cu intake with cognitive decline in the elderly, with an inflection point at approximately 1.3 mg/day of dietary Cu intake., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Floquet (periodic) driving has recently emerged as a powerful technique for engineering quantum systems and realizing nonequilibrium phases of matter. A central challenge to stabilizing quantum phenomena in such systems is the need to prevent energy absorption from the driving field. Fortunately, when the frequency of the drive is significantly larger than the local energy scales of the many-body system, energy absorption is suppressed. The existence of this so-called prethermal regime depends sensitively on the range of interactions and the presence of multiple driving frequencies. Here, we report the observation of Floquet prethermalization in a strongly interacting dipolar spin ensemble in diamond, where the angular dependence of the dipolar coupling helps to mitigate the long-ranged nature of the interaction. Moreover, we extend our experimental observation to quasi-Floquet drives with multiple incommensurate frequencies. In contrast to a single-frequency drive, we find that the existence of prethermalization is extremely sensitive to the smoothness of the applied field. Our results open the door to stabilizing and characterizing nonequilibrium phenomena in quasiperiodically driven systems.

Low response rate of immune checkpoint blockade (ICB) has limited its clinical application. A promising strategy to overcome this limitation is the use of therapeutic cancer vaccines, which aim to induce robust immune responses that synergize with ICB through immune enhancement and immune normalization strategies. Herein, we developed a combination immunotherapy by combining nano-vaccines consisting of whole tumor cell lysates/CpG liposomes (LCLs) with an anti-PD-L1 loaded lipid gel (aPD-L1@LG). The LCLs were fabricated using cationic liposomes, while the lipid gels (LGs) were prepared by using soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO). Subcutaneous administration of LCLs successfully activated dendritic cells (DCs), and intratumoral administration of anti-PD-L1@LG ensured sustained ICB activity. These results demonstrated that this combination immunotherapy enhanced anti-tumor efficacy and prolonged the survival time in melanoma by activating systemic anti-tumor immune responses. These findings highlight the potential of this rational design as a promising strategy for tumor treatment., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2023. Published by Elsevier Inc.)

Background & Aims: The association of dietary intake of carbohydrate (CHO), especially high- and low-quality CHO, with the decline of cognitive function remains uncertain. We aimed to investigate the prospective association of dietary total, low- and high-quality CHO intake with cognitive decline, and further examine the effect of isocaloric substitution with protein or fat, in the elderly population., Methods: A total of 3106 Chinese participants aged ≥55 years from China Health and Nutrition Survey (CHNS) were included in this study. Dietary nutrient intake information was collected by 24-h dietary recalls on 3 consecutive days. The cognitive decline was defined as the 5-year decline rates in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status-modified (TICS-m)., Results: The median follow-up duration was 5.9 years. There was a significantly positive association of dietary low-quality CHO (per 10 percentage energy [%E] increment, β, 0.06; 95%CI, 0.01-0.11) and a no significant association of dietary high-quality CHO (per 10%E increment, β, 0.04; 95%CI, -0.07-0.14) with the 5-year decline rate in the composite cognitive scores. Similar results were found for the global cognitive scores. In model simulations, substituting dietary low-quality CHO with isocaloric animal protein or fat, instead of isocaloric plant protein or fat, was significantly and inversely associated with cognitive decline (All P values < 0.05)., Conclusions: The dietary intake of low-quality CHO, rather than high-quality CHO, was significantly associated with a faster cognitive decline in the elderly. In model simulations, isocaloric substitution of dietary low-quality CHO with animal protein or fat, rather than plant protein or fat, was inversely associated with cognitive decline., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: This cohort study investigated the association between cardiovascular health index scores and pregnancy-induced hypertension (PIH)., Methods: A total of 1466 first-time pregnant women who delivered a single child between 2006 and 2016 were included in the study. All participants underwent a physical examination before delivery, and seven cardiovascular health indexes were collected and scored. Three groups were created based on the tri-sectional quantiles of the total score to observe whether PIH occurred among the groups. A dichotomous logistic regression analysis was carried out to investigate the relationship between cardiovascular health index scores and the occurrence of PIH., Results: During the observation of 1150 subjects, 103 cases of PIH were identified, resulting in an incidence rate of 8.96%. The study found that the incidence of PIH in the three groups was 17.5% in the first group, 6.7% in the second, and 5.8% in the third group. These rates showed a sequential decrease with statistically significant differences (P < .001). The multifactorial regression analysis revealed that after adjusting for various factors, there was a significant inverse relationship between cardiovascular health index scores and the risk of PIH. Specifically, for every one-point increase in the seven cardiovascular health index scores, the risk of PIH decreased by 29% (OR = 0.71, 95% CI 0.59-0.86)., Conclusions: The study found an inverse correlation between cardiovascular health index scores and PIH, with higher scores associated with lower incidences of PIH. Each cardiovascular health indicator helps to lower the risk of PIH, and optimum cardiovascular health behaviors and variables are protective factors against PIH.