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Background/Objectives Chronic kidney disease (CKD) is a global public health problem, including in China. The aim of this study was to identify the risk factors for the development and progression of subclinical renal disease (SRD) in a Chinese population. We also examined whether the impact of the risk factors on SRD changed over time. Subjects/Methods To identify the predictors of SRD, we performed a cross-sectional study of the 2432 subjects in our Hanzhong Adolescent Hypertension Cohort. A subgroup of 202 subjects was further analyzed over a 12-year period from 2005 to 2017 to determine the risk factors for the development and progression of SRD. Results In cross-sectional analysis, elevated blood pressure, male gender, diabetes, body mass index, and triglyceride were independently associated with a higher risk of SRD. In longitudinal analysis, an increase in total cholesterol over a 4-year period and an increase in serum triglyceride over a 12-year period were independently associated with progression of albuminuria. Finally, increases in both total cholesterol and serum uric acid over a 4-year follow-up showed an independent association with a modest reduction in estimated glomerular filtration rate (eGFR). Conclusions In this study of a Chinese cohort, we show several metabolic abnormalities as independent risk factors for subclinical renal disease in a Chinese cohort. In addition, we demonstrate that the effects of total cholesterol, triglycerides and uric acid on the development and progression of albuminuria or the decline in eGFR vary at different points of follow-up. These findings highlight the importance of early detection of metabolic abnormalities to prevent SRD., Author(s): Yang Wang [sup.1] [sup.2] , Ming-Fei Du [sup.1] , Wei-Hua Gao [sup.3] , Bo-Wen Fu [sup.1] , Qiong Ma [sup.1] [sup.2] , Yu Yan [sup.1] [sup.2] , Yue Yuan [...]

Chirality is ubiquitous in nature, and populations of opposite chiralities are surprisingly asymmetric at fundamental levels.sup.1,2. Examples range from parity violation in the subatomic weak force to homochirality in biomolecules. The ability to achieve chirality-selective synthesis (chiral induction) is of great importance in stereochemistry, molecular biology and pharmacology.sup.2. In condensed matter physics, a crystalline electronic system is geometrically chiral when it lacks mirror planes, space-inversion centres or rotoinversion axes.sup.1. Typically, geometrical chirality is predefined by the chiral lattice structure of a material, which is fixed on formation of the crystal. By contrast, in materials with gyrotropic order.sup.3-6, electrons spontaneously organize themselves to exhibit macroscopic chirality in an originally achiral lattice. Although such order--which has been proposed as the quantum analogue of cholesteric liquid crystals--has attracted considerable interest.sup.3-15, no clear observation or manipulation of gyrotropic order has been achieved so far. Here we report the realization of optical chiral induction and the observation of a gyrotropically ordered phase in the transition-metal dichalcogenide semimetal 1T-TiSe.sub.2. We show that shining mid-infrared circularly polarized light on 1T-TiSe.sub.2 while cooling it below the critical temperature leads to the preferential formation of one chiral domain. The chirality of this state is confirmed by the measurement of an out-of-plane circular photogalvanic current, the direction of which depends on the optical induction. Although the role of domain walls requires further investigation with local probes, the methodology demonstrated here can be applied to realize and control chiral electronic phases in other quantum materials.sup.4,16. Optical chiral induction and spontaneous gyrotropic electronic order are realized in the transition-metal chalcogenide 1T-TiSe.sub.2 by using illumination with mid-infrared circularly polarized light and simultaneous cooling below the critical temperature., Author(s): Su-Yang Xu [sup.1] , Qiong Ma [sup.1] , Yang Gao [sup.2] , Anshul Kogar [sup.1] , Alfred Zong [sup.1] , Andrés M. Mier Valdivia [sup.1] , Thao H. Dinh [...]

Background A high atherogenic index of plasma (AIP) is associated with increased cardiovascular risk and higher serum uric acid levels, but whether AIP is a strong risk factor for developing subclinical renal damage (SRD) is unknown. This study aimed to explore the effect of AIP variations on the prevalence of SRD in a 12-year follow-up study. Methods (1) The cross-sectional study enrolled 2485 participants from the Hanzhong cohort in 2017; (2) A total of 202 participants were included in the small longitudinal cohort from 2005 to 2017. Longitudinal analysis was used to determine whether an elevated AIP predicts the development of SRD. Results In the cross-sectional analysis, the AIP level was correlated with the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatine ratio (uACR) (P < 0.05). The age-adjusted odds ratio (OR) for prevalent SRD in men in the high AIP group was 1.924 (1.355-2.732) (P < 0.001), while in women, the OR was 1.616 (1.049-2.490) (P = 0.030) in the high AIP group. In the longitudinal analysis, significantly higher uACR levels were found in participants with normal AIP at baseline and elevated AIP in 2013 (P < 0.05). The adjusted OR for prevalent SRD in the incident AIP group was 4.741 (1.668-13.472) (P = 0.003) compared with the control group. Conclusions Our study indicates that elevated AIP increased the risk of developing SRD and was associated with uACR and eGFR. As a simple marker of CVD risk, AIP may emerge as a novel and reliable indicator of SRD., Author(s): Yue Yuan [sup.1] [sup.2], Jia-Wen Hu [sup.1] [sup.2], Yang Wang [sup.1] [sup.2], Ke-Ke Wang [sup.1] [sup.2], Wen-Ling Zheng [sup.1] [sup.2], Chao Chu [sup.1] [sup.2], Qiong Ma [sup.1] [sup.2], Yu [...]

The electrical Hall effect is the production, upon the application of an electric field, of a transverse voltage under an out-of-plane magnetic field. Studies of the Hall effect have led to important breakthroughs, including the discoveries of Berry curvature and topological Chern invariants.sup.1,2. The internal magnetization of magnets means that the electrical Hall effect can occur in the absence of an external magnetic field.sup.2; this 'anomalous' Hall effect is important for the study of quantum magnets.sup.2-7. The electrical Hall effect has rarely been studied in non-magnetic materials without external magnetic fields, owing to the constraint of time-reversal symmetry. However, only in the linear response regime--when the Hall voltage is linearly proportional to the external electric field--does the Hall effect identically vanish as a result of time-reversal symmetry; the Hall effect in the nonlinear response regime is not subject to such symmetry constraints.sup.8-10. Here we report observations of the nonlinear Hall effect.sup.10 in electrical transport in bilayers of the non-magnetic quantum material WTe.sub.2 under time-reversal-symmetric conditions. We show that an electric current in bilayer WTe.sub.2 leads to a nonlinear Hall voltage in the absence of a magnetic field. The properties of this nonlinear Hall effect are distinct from those of the anomalous Hall effect in metals: the nonlinear Hall effect results in a quadratic, rather than linear, current-voltage characteristic and, in contrast to the anomalous Hall effect, the nonlinear Hall effect results in a much larger transverse than longitudinal voltage response, leading to a nonlinear Hall angle (the angle between the total voltage response and the applied electric field) of nearly 90 degrees. We further show that the nonlinear Hall effect provides a direct measure of the dipole moment.sup.10 of the Berry curvature, which arises from layer-polarized Dirac fermions in bilayer WTe.sub.2. Our results demonstrate a new type of Hall effect and provide a way of detecting Berry curvature in non-magnetic quantum materials.The nonlinear Hall effect is observed in bilayer WTe.sub.2 in the absence of a magnetic field, providing a direct measure of the dipole moment of the Berry curvature., Author(s): Qiong Ma [sup.1] , Su-Yang Xu [sup.1] , Huitao Shen [sup.1] , David MacNeill [sup.1] , Valla Fatemi [sup.1] , Tay-Rong Chang [sup.2] , Andrés M. Mier Valdivia [sup.1] [...]

Recent evidence suggests that necroptosis may contribute to the development of kidney injury. Renalase is a novel secretory protein that exerts potent prosurvival and anti-inflammatory effects. We hypothesized that renalase could protect the kidney from salt-induced injury by modulating necroptosis. High salt and renalase treatments were administered to Dahl salt-sensitive (SS) rats, renalase knockout (KO) mice, and HK-2 cells. Furthermore, a cohort of 514 eligible participants was utilized to investigate the association between single nucleotide polymorphisms (SNPs) in the genes RIPK1, RIPK3, and MLKL, and the risk of subclinical renal damage (SRD) over 14 years. A high-salt diet significantly increased the expression of key components of necroptosis, namely RIPK1, RIPK3, and MLKL, as well as the release of inflammatory factors in SS rats. Treatment with recombinant renalase reduced both necroptosis and inflammation. In renalase KO mice, salt-induced kidney injury was more severe than in wild-type mice, but supplementation with renalase attenuated the kidney injury. In vitro experiments with HK-2 cells revealed high salt increased necroptosis and inflammation. Renalase exhibited a dose-dependent decrease in salt-induced necroptosis, and this cytoprotective effect was negated by the knockdown of PMCA4b, which is the receptor of renalase. Furthermore, the cohort study showed that SNP rs3736724 in RIPK1 and rs11640974 in MLKL were significantly associated with the risk of SRD over 14 years. Our analysis shows that necroptosis plays a significant role in the development of salt-induced kidney injury and that renalase confers its cytoprotective effects by inhibiting necroptosis and inflammation., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The convergence of topology and correlations represents a highly coveted realm in the pursuit of new quantum states of matter 1 . Introducing electron correlations to a quantum spin Hall (QSH) insulator can lead to the emergence of a fractional topological insulator and other exotic time-reversal-symmetric topological order 2-8 , not possible in quantum Hall and Chern insulator systems. Here we report a new dual QSH insulator within the intrinsic monolayer crystal of TaIrTe 4 , arising from the interplay of its single-particle topology and density-tuned electron correlations. At charge neutrality, monolayer TaIrTe 4 demonstrates the QSH insulator, manifesting enhanced nonlocal transport and quantized helical edge conductance. After introducing electrons from charge neutrality, TaIrTe 4 shows metallic behaviour in only a small range of charge densities but quickly goes into a new insulating state, entirely unexpected on the basis of the single-particle band structure of TaIrTe 4 . This insulating state could arise from a strong electronic instability near the van Hove singularities, probably leading to a charge density wave (CDW). Remarkably, within this correlated insulating gap, we observe a resurgence of the QSH state. The observation of helical edge conduction in a CDW gap could bridge spin physics and charge orders. The discovery of a dual QSH insulator introduces a new method for creating topological flat minibands through CDW superlattices, which offer a promising platform for exploring time-reversal-symmetric fractional phases and electromagnetism 2-4,9,10 ., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Moiré quantum materials host exotic electronic phenomena through enhanced internal Coulomb interactions in twisted two-dimensional heterostructures 1-4 . When combined with the exceptionally high electrostatic control in atomically thin materials 5-8 , moiré heterostructures have the potential to enable next-generation electronic devices with unprecedented functionality. However, despite extensive exploration, moiré electronic phenomena have thus far been limited to impractically low cryogenic temperatures 9-14 , thus precluding real-world applications of moiré quantum materials. Here we report the experimental realization and room-temperature operation of a low-power (20 pW) moiré synaptic transistor based on an asymmetric bilayer graphene/hexagonal boron nitride moiré heterostructure. The asymmetric moiré potential gives rise to robust electronic ratchet states, which enable hysteretic, non-volatile injection of charge carriers that control the conductance of the device. The asymmetric gating in dual-gated moiré heterostructures realizes diverse biorealistic neuromorphic functionalities, such as reconfigurable synaptic responses, spatiotemporal-based tempotrons and Bienenstock-Cooper-Munro input-specific adaptation. In this manner, the moiré synaptic transistor enables efficient compute-in-memory designs and edge hardware accelerators for artificial intelligence and machine learning., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowers blood pressure (BP) and exert a salutary effect on the salt sensitivity of BP. This study aimed to examine the associations of SGLT2 genetic variants with salt sensitivity, longitudinal BP changes and the risk of incident hypertension in Baoji Salt-Sensitive Study. A total of 514 participants were recruited when the cohort was established in 2004, and 333 participants received a dietary intervention that consisted of a 3-day usual diet followed sequentially by a 7-day low-salt diet and a 7-day high-salt diet. The cohort was then followed up for 14 years to evaluate the longitudinal BP changes and development of hypertension. We found that SGLT2 SNP rs3813007 was significantly associated with the systolic BP (SBP) responses to the low-salt diet. Over the 14 years of follow-up, SNPs rs3116149 and rs3813008 were significantly associated with the longitudinal SBP changes, and SNPs rs3116149, rs3813008, rs3813007 in SGLT2 were significantly associated with incidence of hypertension. Furthermore, gene-based analyses revealed that SGLT2 was significantly associated with hypertension incidence. Our study suggests that SGLT2 genetic polymorphisms may be involved in salt sensitivity and development of hypertension., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Whereas ferromagnets have been known and used for millennia, antiferromagnets were only discovered in the 1930s 1 . At large scale, because of the absence of global magnetization, antiferromagnets may seem to behave like any non-magnetic material. At the microscopic level, however, the opposite alignment of spins forms a rich internal structure. In topological antiferromagnets, this internal structure leads to the possibility that the property known as the Berry phase can acquire distinct spatial textures 2,3 . Here we study this possibility in an antiferromagnetic axion insulator-even-layered, two-dimensional MnBi 2 Te 4 -in which spatial degrees of freedom correspond to different layers. We observe a type of Hall effect-the layer Hall effect-in which electrons from the top and bottom layers spontaneously deflect in opposite directions. Specifically, under zero electric field, even-layered MnBi 2 Te 4 shows no anomalous Hall effect. However, applying an electric field leads to the emergence of a large, layer-polarized anomalous Hall effect of about 0.5e 2 /h (where e is the electron charge and h is Planck's constant). This layer Hall effect uncovers an unusual layer-locked Berry curvature, which serves to characterize the axion insulator state. Moreover, we find that the layer-locked Berry curvature can be manipulated by the axion field formed from the dot product of the electric and magnetic field vectors. Our results offer new pathways to detect and manipulate the internal spatial structure of fully compensated topological antiferromagnets 4-9 . The layer-locked Berry curvature represents a first step towards spatial engineering of the Berry phase through effects such as layer-specific moiré potential., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The constituent particles of matter can arrange themselves in various ways, giving rise to emergent phenomena that can be surprisingly rich and often cannot be understood by studying only the individual constituents. Discovering and understanding the emergence of such phenomena in quantum materials-especially those in which multiple degrees of freedom or energy scales are delicately balanced-is of fundamental interest to condensed-matter research 1,2 . Here we report on the surprising observation of emergent ferroelectricity in graphene-based moiré heterostructures. Ferroelectric materials show electrically switchable electric dipoles, which are usually formed by spatial separation between the average centres of positive and negative charge within the unit cell. On this basis, it is difficult to imagine graphene-a material composed of only carbon atoms-exhibiting ferroelectricity 3 . However, in this work we realize switchable ferroelectricity in Bernal-stacked bilayer graphene sandwiched between two hexagonal boron nitride layers. By introducing a moiré superlattice potential (via aligning bilayer graphene with the top and/or bottom boron nitride crystals), we observe prominent and robust hysteretic behaviour of the graphene resistance with an externally applied out-of-plane displacement field. Our systematic transport measurements reveal a rich and striking response as a function of displacement field and electron filling, and beyond the framework of conventional ferroelectrics. We further directly probe the ferroelectric polarization through a non-local monolayer graphene sensor. Our results suggest an unconventional, odd-parity electronic ordering in the bilayer graphene/boron nitride moiré system. This emergent moiré ferroelectricity may enable ultrafast, programmable and atomically thin carbon-based memory devices.

There is currently a lack of strong evidence linking childhood elevated blood pressure to long-term cardiovascular risk in adulthood. Repeated observations of abnormal blood pressure in childhood may enhance the prediction of cardiovascular risk in adulthood compared with a single observation. The study included 1738 individuals in rural areas of Hanzhong City, Shaanxi, who had been followed for 30 years since baseline (1987, at which time participants were aged 6-15 years). According to four independent measurements of blood pressure in 1987, 1989, 1992, and 1995, childhood elevated blood pressure was defined as 2 in-person examinations with blood pressure values above the 90th percentile. Arterial stiffness and left ventricular hypertrophy in adulthood were assessed by brachial-ankle pulse wave velocity and the Cornell product index, respectively. Childhood elevated blood pressure was associated with an increased risk of adult hypertension (OR, 2.01; 95% CI, 1.53-2.65), arterial stiffness (OR, 1.69; 95% CI, 1.32-2.16) and left ventricular hypertrophy (OR, 1.86; 95% CI, 1.13-3.05) (all P < 0.05). Cardiovascular risk in adults increased with increasing childhood blood pressure levels. In addition, two abnormal childhood blood pressure observations predicted an increased likelihood of hypertension in adulthood (0.77 for 2 versus 0.70 for 1 observation, P < 0.001). Our study provides strong evidence that elevated blood pressure in childhood predicts cardiovascular risk in adults. The prediction was enhanced by two observations of abnormal blood pressure in childhood compared with a single measurement. We emphasize the importance of childhood blood pressure monitoring and control in the prevention of cardiovascular diseases.

High uric acid (UA) level and high salt intake are reportedly associated with cardiovascular disease. This study investigated the association between UA and urinary sodium excretion, as well as its interaction on the risk of prehypertension. A total of 1869 participants without hypertension were recruited from a previously established cohort in Shaanxi Province, China. The participants were classified as normotensive or prehypertensive on the basis of their blood pressure. Increasing quartiles of sodium excretion were associated with high urinary UA/creatinine levels in prehypertensive participants. Estimated sodium excretion positively correlated with urinary UA/creatinine excretions in the prehypertensive group. In addition, the multivariate-adjusted odds ratios for prehypertension compared with normotension were 1.68 (1.27-2.22) for sodium excretion and 1.71 (1.21-2.42) for serum UA. Increasing sodium excretion and serum UA were associated with higher risk of prehypertension. Compared with the lowest quartiles, the highest sodium excretion and serum UA quartiles entailed 3.48 times greater risk of prehypertension. Sodium excretion is associated with urinary UA excretion in prehypertensive participants. The present study shows that high levels of salt intake and serum UA simultaneously are associated with a higher risk of prehypertension.

Recent studies have reported the association between endothelial nitric oxide synthase (eNOS) gene G894T polymorphism and pregnancy-induced hypertension (PIH). However, the results have been inconsistent. We conducted a comprehensive meta-analysis to explore this association. A total of 36 case-control studies involving 4028 PIH cases and 7672 controls were ultimately included. In the overall analysis, no association was identified between eNOS gene G894T polymorphism and PIH risk in any of the genetic models. In the subgroup analysis, the results showed that T-allele carriers had a higher risk of PIH than those with the G allele in Asians (G vs. T: odds ratio (OR)=0.76, 95% confidence interval (CI)=0.63-0.91, P=0.002; GT+TT vs. GG: OR=1.32, 95% CI=1.09-1.59, P=0.004; TT vs. GT+GG: OR=1.96, 95% CI=1.26-3.06, P=0.003; TT vs. GG: OR=1.99, 95% CI=1.27-3.11, P=0.003; GT vs. GG: OR=1.23, 95% CI=1.05-1.43, P=0.009). For Latin American and African populations, the association between G894T polymorphism and susceptibility to PIH was only observed in the dominant model. However, no association was observed in Europeans and Americans. Therefore, eNOS gene G894T polymorphism was related to PIH risk, especially for Asians.

Different clinical results have been reported in the repair of extensor mechanism disruption using fresh-frozen complete extensor mechanism (CEM) allograft, creating a need for a better understanding of fresh-frozen CME allograft reconstruction. Here, we perform histological and biomechanical analyses of fresh-frozen CEM allograft or autograft reconstruction in an in vivo rabbit model. Our histological results show complete incorporation of the quadriceps tendon into the host tissues, patellar survival and total integration of the allograft tibia, with relatively fewer osteocytes, into the host tibia. Vascularity and cellularity are reduced and delayed in the allograft but exhibit similar distributions to those in the autograft. The infrapatellar fat pad provides the main blood supply, and the lowest cellularity is observed in the patellar tendon close to the tibia in both the allograft and autograft. The biomechanical properties of the junction of quadriceps tendon and host tissues and those of the allograft patellar tendon are completely and considerably restored, respectively. Therefore, fresh-frozen CEM allograft reconstruction is viable, but the distal patellar tendon and the tibial block may be the weak links of the reconstruction. These findings provide new insight into the use of allograft in repairing disruption of the extensor mechanism.

CXCR4 is expressed at primary and metastatic sites of osteosarcoma. We developed a novel CXCR4-targeted near-infrared (NIR) fluorescent imaging agent (referred to as CXCR4-IR-783). The binding to representative osteosarcoma cells (F5M2 and F4 for high- and low- CXCR4 expression) was examined. CXCR4-IR-783 fluorescence was also examined in a mouse xenograft model of human osteosarcoma using NIR fluorescence microscopy and a Kodak in-vivo multispectral system. Pulmonary metastases in mice bearing osteosarcoma xenografts were detected by micro CT, (18)F-PET scan and NIR imaging scan. Briefly, the binding of CXCR4-IR-783 was significantly higher in F5M2 than in F4 cells. Intense NIR fluorescence signals were detected in osteosarcoma xenografts, with signal/background ratio at 4.87 in mice bearing the F5M2 cell. At 4 weeks after F5M2 cell inoculation, metastatic lesions in the lungs were detectable using CXCR4-IR-783 and micro-CT scan, but not with (18)F-FDG PET scan. In conclusion, CXCR4-IR-783 is a promising tool for detection of high CXCR4-expressing osteosarcoma, and particularly for its metastatic lesions.