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Abstract Background NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. Methods Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. Results Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P

Abstract Cervical cancer (CC) remains a major health concern globally, much of the brunt of which is experienced by the low- and middle-income countries where screening in terms of cytology and DNA genotyping for the high-risk oncogenic subtypes of the human papilloma virus (hr-HPV) is either inadequate or performed rather late. In this study, we aimed to determine biomarkers or panels of biomarkers that are capable of diagnosing the precancerous cervical intraepithelial neoplasia (CIN) stages from healthy and CC patients via untargeted gas chromatography–mass spectrometry-based metabolomics. Various cross-comparisons were conducted from which differential metabolites were identified. The underlying metabolic pathways based on the differential metabolites identified from the various cross-comparisons mainly related to amino acids biosynthesis and metabolism and steroid hormone biosynthesis. From all cross-comparisons, two common metabolites namely, 2-methyl-1-propylamine (also known as isobutylamine) and estrone were found to possess excellent to good diagnostic abilities, especially in distinguishing the early stages of CIN (CIN I, CIN II) from healthy women and CC patients. These findings have clinical significance in the sense that, once validated the 2-biomarker panel could be adopted in clinical practice for early diagnosis of CIN and invasive carcinoma. This would therefore inform the choice of treatment to be initiated by the clinician.

Abstract Lattice-based digital signature has become one of the widely recognized post-quantum algorithms because of its simple algebraic operation, rich mathematical foundation and worst-case security, and also an important tool for constructing cryptography. This survey explores lattice-based digital signatures, a promising post-quantum resistant alternative to traditional schemes relying on factoring or discrete logarithm problems, which face increasing risks from quantum computing. The study covers conventional paradigms like Hash-and-Sign and Fiat-Shamir, as well as specialized applications including group, ring, blind, and proxy signatures. It analyzes the versatility and security strengths of lattice-based schemes, providing practical insights. Each chapter summarizes advancements in schemes, identifying emerging trends. We also pinpoint future directions to deploy lattice-based digital signatures including quantum cryptography.

Brain microstructural alterations possibly occur in the normal-appearing white matter (NAWM) and grey matter of small vessel disease (SVD) patients, and may contribute to cognitive impairment. The aim of this study was to explore cognitive related microstructural alterations in white matter and deep grey matter nuclei in SVD patients using magnetic resonance (MR) quantitative susceptibility mapping (QSM). 170 SVD patients, including 103 vascular mild cognitive impairment (VaMCI) and 67 no cognitive impairment (NCI), and 21 healthy control (HC) subjects were included, all underwent a whole-brain QSM scanning. Using a white matter and a deep grey matter atlas, subregion-based QSM analysis was conducted to identify and characterize microstructural alterations occurring within white matter and subcortical nuclei. Significantly different susceptibility values were revealed in NAWM and in several specific white matter tracts including anterior limb of internal capsule, corticospinal tract, medial lemniscus, middle frontal blade, superior corona radiata and tapetum among VaMCI, NCI and HC groups. However, no difference was found in white matter hyperintensities between VaMCI and NCI. A trend toward higher susceptibility in the caudate nucleus and globus pallidus of VaMCI patients compared to HC, indicating elevated iron deposition in these areas. Interestingly, some of these QSM parameters were closely correlated with both global and specific cognitive function scores, controlling age, gender and education level. Our study suggested that QSM may serve as a useful imaging tool for monitoring cognitive related microstructural alterations in brain. This is especially meaningful for white matter which previously lacks of attention.

Chronic Kidney Disease (CKD), closely linked to environmental factors, poses a significant public health challenge. This study, based on 529 triple-repeated measures from key national environmental pollution area and multiple gene-related public databases, employs various epidemiological and bioinformatics models to assess the impact of combined heavy metal exposure (Chromium [Cr], Cadmium [Cd], and Lead [Pb]) on early renal injury and CKD in the elderly. Introducing the novel Enviro-Target Mendelian Randomization method, our research explores the causal relationship between metals and CKD. The findings indicate a positive correlation between increased levels of metal and renal injury, with combined exposure caused renal damage more significantly than individual exposure. The study reveals that metals primarily influence CKD development through oxidative stress and metal ion resistance pathways, focusing on three related genes (SOD2, MPO, NQO1) and a transcription factor (NFE2L2). Metals were found to regulate oxidative stress levels in the body by increasing the expression of SOD2, MPO, NQO1, and decreasing NFE2L2, leading to CKD onset. Our research establishes a new causal inference framework linking environmental pollutants-pathways-genes-CKD, assessing the impact and mechanisms of metal exposure on CKD. Future studies with more extensive in vitro evidence and larger population are needed to validate.

PurposeEmploying free water (FW) imaging, a cutting-edge diffusion MRI technique, we assessed neuroinflammation within deep gray matter (DGM) in small vessel disease (SVD) over 1–2 years.MethodOne hundred and seventy SVD patients and 21 healthy controls (HCs) underwent MRI scans and neuropsychological evaluations at baseline. These patients were then categorized into two groups: 67 displayed no cognitive impairment (NCI), while 103 exhibited vascular mild cognitive impairment (VaMCI). A follow-up study 1–2 years later included 23 from the NCI group and 28 from the VaMCI group. Calculation of FW values within DGM facilitated both cross-sectional and longitudinal analysis, revealing partial correlations between FW value changes and cognitive function alternations.ResultsBaseline examinations disclosed significant differences in DGM FW values among the three participant groups. We found increased mean FW values in the left pulvinar (Pul), bilateral lateral nuclei (LN) and bilateral internal medullary lamina of the thalamus in VaMCI participants compared with their NCI counterparts in longitudinal analysis. Notably, negative associations emerged between the FW value changes in the left Pul and the right LN of the thalamus and MoCA score changes in the VaMCI group over 1–2 years.ConclusionsThese findings support the hypothesis that increased FW value is present at the preclinical stage of SVD and remains persistent during the early course of the disease, potentially acting as the biomarker for the mechanism of underlying cognitive decline in SVD.

With strong electron–phonon coupling, self‐trapped excitons (STEs) are typically formed in perovskite materials, and radiative recombination of STEs can produce broadband emission with large Stokes shifts. STEs are essential to further improve the optoelectronic properties of materials. Surprisingly, 2D system is the edge case, with low even no self‐trapping barriers, leading to effortless formation of STEs. In this work, 2D strontium titanate (SrTiO3) with defects is prepared using supercritical carbon dioxide (SC CO2) and its carrier transport and transition are studied. The appearance of wide photoinduced positive absorption signals in the femtosecond transient absorption spectra is direct evidence for the formation of STEs. The presence of STEs is further supported by the increased Stokes shift and full width at half maximum in the steady‐state photoluminescence spectra.

Background: Epidemiological studies have reported associations between heavy metals and renal function. However, longitudinal studies are required to further validate these associations and explore the interactive effects of heavy metals on renal function and their directional influence. Method: This study, conducted in Northeast China from 2016 to 2021, included a four-time repeated measures design involving 384 participants (1536 observations). Urinary concentrations of chromium (Cr), cadmium (Cd), manganese (Mn), and lead (Pb) were measured, along with renal biomarkers including urinary microalbumin (umAlb), urinary albumin-to-creatinine ratio (UACR), N-acetyl-β-D-glucosaminidase (NAG), and β2-microglobulin (β2-MG) levels. Estimated glomerular filtration rate (eGFR) was calculated. A Linear Mixed Effects Model (LME) examined the association between individual metal exposure and renal biomarkers. Subsequently, Quantile g-computation and Bayesian Kernel Machine Regression (BKMR) models assessed the overall effects of heavy metal mixtures. Marginal Effect models examined the directional impact of metal interactions in the BKMR on renal function. Result: Results indicate significant impacts of individual and combined exposures of Cr, Cd, Pb, and Mn on renal biomarkers. Metal interactions in the BKMR model were observed, with synergistic effects of Cd-Cr on NAG, umAlb, UACR; Cd-Pb on NAG, UACR; Pb-Cr on umAlb, UACR, eGFR-MDRD, eGFR-EPI; and an antagonistic effect of Mn-Pb-Cr on UACR. Conclusion: Both individual and combined exposures to heavy metals are associated with renal biomarkers, with significant synergistic interactions leading to renal damage. Our findings elucidate potential interactions among these metals, offering valuable insights into the mechanisms linking multiple metal exposures to renal injury.

Abstract Graphene has a long spin lifetime and hyperfine interactions, favoring its potential application as spintronics. Despite the recent discoveries of spin‐containing graphene materials, graphene‐based materials with room‐temperature macroscopic ferromagnetism are extremely rare. In this article, room‐temperature ferromagnetic amorphous graphene oxide (GO) is synthesized by introducing abundant oxygen‐containing functional groups and C defects into single‐layered graphene, followed by a self‐assembly process under supercritical CO2 (SC CO2). Such amorphous GO exhibits the highest saturation magnetization (1.71 emu g−1) and remanent magnetization (0.251 emu g−1) compared to the rest of metal‐free graphene‐based materials at room temperature. Experimental and theoretical investigations attribute such strong ferromagnetism to the bridging of the adjacent graphene layers though the out‐of‐plane oxygen‐containing groups, which leads to asymmetric lattices with large net magnetic moments.

Background: The impact of heavy metals on liver function has been examined in numerous epidemiological studies. However, these findings lack consistency and longitudinal validation. Methods: In this study, we conducted three follow-up surveys with 426 participants from Northeast China. Blood and urine samples were collected, along with questionnaire information. Urine samples were analyzed for concentrations of four metals (chromium [Cr], cadmium [Cd], lead [Pb], and manganese [Mn]), while blood samples were used to measure five liver function indicators (alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin [ALB], globulin [GLB], and total protein [TP]). We utilized a linear mixed-effects model (LME) to explore the association between individual heavy metal exposure and liver function. Joint effects of metal mixtures were investigated using quantile g-computation and Bayesian kernel machine regression (BKMR). Furthermore, we employed BKMR and Marginal Effect models to examine the interaction effects between metals on liver function. Results: The LME results demonstrated a significant association between urinary heavy metals (Cr, Cd, Pb, and Mn) and liver function markers. BKMR results indicated positive associations between heavy metal mixtures and ALT, AST, and GLB, and negative associations with ALB and TP, which were consistent with the g-comp results. Synergistic effects were observed between Cd-Cr on ALT, Mn-Cr and Cr-Pb on ALB, while an antagonistic effect was found between Mn-Pb and Mn-Cd on ALB. Additionally, synergistic effects were observed between Mn-Cr on GLB and Cd-Cr on TP. Furthermore, a three-way antagonistic effect of Mn-Pb-Cr on ALB was identified. Conclusion: Exposure to heavy metals (Cr, Cd, Mn, Pb) is associated with liver function markers, potentially leading to liver damage. Moreover, there are joint and interaction effects among these metals, which warrant further investigation at both the population and mechanistic levels.

Abstract The pressing crisis of clean water shortage requires membranes to possess effective ion sieving as well as fast water flux. However, effective ion sieving demands reduction of pore size, which inevitably hinders water flux in hydrophilic membranes, posing a major challenge for efficient water/ion separation. Herein, we introduce anomalous water molecular gating based on nanofiltration membranes full of graphene capillaries at 6 Å, which were fabricated from spontaneous π-π restacking of island-on-nanosheet graphitic microstructures. We found that the membrane can provide effective ion sieving by suppressing osmosis-driven ion diffusion to negligible levels (~10–4 mol m–2 h–1); unexpectedly, ultrafast bulk flow of water (45.4 L m–2 h–1) was still functional with ease, as gated on/off by adjusting hydrostatic pressures within only 10–2 bar. We attribute this seemingly incompatible observation to graphene nanoconfinement effect, where crystal-like water confined within the capillaries hinders diffusion under osmosis but facilitates high-speed, diffusion-free water transport in the way analogous to Newton’s cradle-like Grotthus conduction. This strategy establishes a type of liquid-solid-liquid, phase-changing molecular transport for precise and ultrafast molecular sieving.

To improve the forecast accuracy of heavy precipitation, re-forecasts are conducted for the Henan 21.7 rainstorm. The Intermediate Complexity Atmospheric Research Model (ICAR) and the Weather Research and Forecasting Model (WRF) with a 1 km horizontal grid spacing are used for the re-forecasts. The results indicate that heavy precipitation forecasted by ICAR primarily accumulates on the windward slopes of the mountains. In contrast, some severe precipitation forecasted by WRF is beyond the mountains. The main difference between ICAR and WRF is that ICAR excludes the “impacts of physical processes on winds and the nonlinear interactions between the small resolvable-scale disturbances” (briefed as the “physical–dynamical interactions”). Thus, heavy precipitation beyond the mountains is attributed to the “physical–dynamical interactions”. Furthermore, severe precipitation on the windward slopes of the mountains typically aligns with the observations, whereas heavy rainfall beyond the mountains seldom matches the observations. Therefore, severe precipitation on the windward slopes of (beyond) the mountains is more (less) predictable. Based on these findings and theoretical thinking about the predictability of severe precipitation, a scheme of using the ICAR’s prediction to adjust the WRF’s prediction is proposed, thereby improving the forecast accuracy of heavy rainfall.

Abstract 2D nanomaterials play a critical role in realizing high‐performance flexible electrodes for wearable energy storge devices, owing to their merits of large surface area, high conductivity and high strength. The electrode is a complex system and the performance is determined by multiple and interrelated factors including the intrinsic properties of materials and the structures at different scales from macroscale to atomic scale. Multiscale design strategies have been developed to engineer the structures to exploit full potential and mitigate drawbacks of 2D materials. Analyzing the design strategies and understanding the working mechanisms are essential to facilitate the integration and harvest the synergistic effects. This review summarizes the multiscale design strategies from macroscale down to micro/nano‐scale structures and atomic‐scale structures for developing 2D nanomaterials‐based flexible electrodes. It starts with brief introduction of 2D nanomaterials, followed by analysis of structural design strategies at different scales focusing on the elucidation of structure‐property relationship, and ends with the presentation of challenges and future prospects. This review highlights the importance of integrating multiscale design strategies. Finding from this review may deepen the understanding of electrode performance and provide valuable guidelines for designing 2D nanomaterials‐based flexible electrodes.

Abstract With humongous demand for data storage and processing, two‐dimensional (2D) ferromagnetic‐based materials, is emerged as the next‐generation nanoelectronic devices due to their low power consumption and optimal memory and processing capabilities. BiFeO3 as a single‐phase multiferromagnetic material is expected to find potential applications in electromagnetic devices. Herein, 2D room‐temperature ferromagnetic BiFeO3 is obtained with the help of supercritical carbon dioxide (SC CO2). The rhombic phase of BiFeO3 is converted to cubic with the creation of Ov and Fe2+ defects over the SC CO2 treatment, leading to significant ferromagnetic enhancement. More importantly, it is found that SC CO2 can destroy the cycloidal spin structure of BiFeO3 leading to an increase in the Fe─O─Fe bond angle, which generates stronger superexchange interactions. Ultimately, the saturation magnetization strength of BiFeO3 is increased by nearly 23 times. A new strategy is provided for ferromagnetic induction in 2D materials, which is favorable for promoting their practical applications on device architectures in the future.

Abstract The preparation of 2D magnetoelectric (ME) nanomaterials with strong ME coupling is crucial for the fast reading and writing processes in the next generation of storage devices. Herein, 2D BaTiO3 (BTO)‐CoFe2O4 (CFO) ME nanocomposites are prepared through a substrate‐free coupling strategy using supercritical CO2. Such 2D BTO‐CFO with strong coupling is built through alternating in‐plane and out‐of‐plane epitaxy stacking, leading to remarkable mutual biaxial strain effects for spin‐lattice coupling. As a results, such strain effect significantly enhances the ferroelectricity of BTO and the ferrimagnetism of CFO, where an unexceptionally high ME coupling coefficient of (325.8 mV cm−1 Oe−1) is obtained for the BTO‐CFO nanocomposites.

To enhance the reproducibility of motor unit number index (MUNIX) for evaluating neurological disease progression, this paper proposes a negative entropy-based fast independent component analysis (FastICA) demixing method to assess MUNIX reproducibility in the presence of inter-channel mixing of electromyography (EMG) signals acquired by high-density electrodes. First, composite surface EMG (sEMG) signals were obtained using high-density surface electrodes. Second, the FastICA algorithm based on negative entropy was employed to determine the orthogonal projection matrix that minimizes the negative entropy of the projected signal and effectively separates mixed sEMG signals. Finally, the proposed experimental approach was validated by introducing an interrelationship criterion to quantify independence between adjacent channel EMG signals, measuring MUNIX repeatability using coefficient of variation (CV), and determining motor unit number and size through MUNIX. Results analysis shows that the inclusion of the full (128) channel sEMG information leads to a reduction in CV value by $1.5 \pm 0.1$ and a linear decline in CV value with an increase in the number of channels. The correlation between adjacent channels in participants decreases by $0.12 \pm 0.05$ as the number of channels gradually increases. The results demonstrate a significant reduction in the number of interrelationships between sEMG signals following negative entropy-based FastICA processing, compared to the mixed sEMG signals. Moreover, this decrease in interrelationships becomes more pronounced with an increasing number of channels. Additionally, the CV of MUNIX gradually decreases with an increase in the number of channels, thereby optimizing the issue of abnormal MUNIX repeatability patterns and further enhancing the reproducibility of MUNIX based on high-density surface EMG signals.

Abstract Despite the remarkable progress made in perovskite solar cells, great concerns regarding potential Pb contamination risk and environmental vulnerability risks associated with perovskite solar cells pose a significant obstacle to their real-world commercialization. In this study, we took inspiration from the ensnaring prey behavior of spiders and chemical components in spider web to strategically implant a multifunctional mesoporous amino-grafted-carbon net into perovskite solar cells, creating a biomimetic cage traps that could effectively mitigate Pb leakage and shield the external invasion under extreme weather conditions. The synergistic Pb capturing mechanism in terms of chemical chelation and physical adsorption is in-depth explored. Additionally, the Pb contamination assessment of end-of-life perovskite solar cells in the real-world ecosystem, including Yellow River water and soil, is proposed. The sustainable closed-loop Pb management process is also successfully established involving four critical steps: Pb precipitation, Pb adsorption, Pb desorption, and Pb recycling. Our findings provide inspiring insights for promoting green and sustainable industrialization of perovskite solar cells.

Because plant mechanical strength influences plant growth and development, the regulatory mechanisms underlying cell-wall synthesis deserve investigation. Rice mutants are useful for such research. We have identified a novel brittle culm 25 (bc25) mutant with reduced growth and partial sterility. BC25 encodes an UDP-glucuronic acid decarboxylase involved in cellulose synthesis and belongs to the UXS family. A single-nucleotide mutation in BC25 accounts for its altered cell morphology and cell-wall composition. Transmission electron microscopy analysis showed that the thickness of the secondary cell wall was reduced in bc25. Monosaccharide analysis revealed significant increases in content of rhamnose and arabinose but not of other monosaccharides, indicating that BC25 was involved in xylose synthesis with some level of functional redundancy. Enzymatic assays suggested that BC25 functions with high activity to interconvert UDP-glucuronic acid (UDP-GlcA) and UDP-xylose. GUS staining showed that BC25 was ubiquitously expressed with higher expression in culm, root and sheath, in agreement with that shown by quantitative real-time (qRT)-PCR. RNA-seq further suggested that BC25 is involved in sugar metabolism. We conclude that BC25 strongly influences rice cell wall formation.

Abstract Two-dimensional (2D) metal-free ferromagnetic materials are ideal candidates to fabricate next-generation memory and logic devices, but optimization of their ferromagnetism at atomic-scale remains challenging. Theoretically, optimization of ferromagnetism could be achieved by inducing long-range magnetic sequence, which requires short-range exchange interactions. In this work, we propose a strategy to enhance the ferromagnetism of 2D graphite carbon nitride (g-C3N4), which is facilitating the short-range exchange interaction by introducing in-planar boron bridges. As expected, the ferromagnetism of g-C3N4 was significantly enhanced after the introduction of boron bridges, consistent with theoretical calculations. Overall, boosting ferromagnetism of 2D materials by introducing bridging groups is emphasized, which could be applied to manipulate the magnetism of other materials.

Sarcopenia involves in the loss of muscle mass associated with aging, which is the major cause of progressive muscle weakness and deterioration in older adults. Muscle atrophy is a direct presentation of sarcopenia, and it greatly contributes to the decline in quality of life among older adults. Neuromuscular junction (NMJ) stability is the key link to maintain muscle function. Besides, the degenerative change of NMJ promotes the process of muscle atrophy in the elderly. Based on previous transcriptome sequencing and bioinformatics analyses of aged muscle, this study used the 18-month-old aged mouse model and the 6-month-old young mouse model to deliberate the role and underlying mechanisms of Cullin-3 (Cul3) in age-related muscle atrophy. The results of reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblotting analysis showed that the expression of CUL3 increased in aged muscle tissue, while the expression level of postsynaptic membrane nicotinic acetylcholine receptors (nAChRs) decreased significantly, which manfested a negative correlation. Meanwhile, immunofluorescence demonstrated that Cul3 was highly expressed in senile muscle NMJ. The results of ubiquitin indicated that the ubiquitin level of aged muscle nAChRs was evidently increased. Co-immunoprecipitation furtherly verified the correlation between Cul3 and nAChRs. Taken together, Cul3 may mediate the ubiquitination degradation of nAChRs protein at the NMJ site in aged mice, leading to NMJ degeneration and accelerated atrophy of fast-twitch muscle fibers in aged muscle. As a prominent element to maintain the stability of NMJ, Cul3 is supposed to be one of candidate intervention targets in sarcopenia.

Repeatability is an important attribute of motor unit number index (MUNIX) technology. This paper proposes an optimal contraction force combination for MUNIX calculation in an effort to improve the repeatability of this technology. In this study, the surface electromyography (EMG) signals of the biceps brachii muscle of eight healthy subjects were initially recorded with high-density surface electrodes, and the contraction strength was the maximum voluntary contraction force of nine progressive levels. Then, by traversing and comparing the repeatability of MUNIX under various combinations of contraction force, the optimal combination of muscle strength is determined. Finally, calculate MUNIX using the high-density optimal muscle strength weighted average method. The correlation coefficient and the coefficient of variation are utilized to assess repeatability. The results show that when the muscle strength combination is 10, 20, 50 and 70% of the maximum voluntary contraction force, the repeatability of MUNIX is greatest, and the correlation between MUNIX calculated using this combination of muscle strength and conventional methods is high (PCC > 0.99), the repeatability of the MUNIX method improved by 11.5–23.8%. The results indicate that the repeatability of MUNIX differs for various combinations of muscle strength and that MUNIX, which is measured with a smaller number and lower-level contractility, has greater repeatability.

Patients with Alzheimer’s disease (AD) often present with imaging features indicative of small-vessel injury, among which, white-matter hyperintensities (WMHs) are the most prevalent. However, the underlying mechanism of the association between AD and small-vessel injury is still obscure. The aim of this study is to investigate the mechanism of small-vessel injury in AD. Differential gene expression analyses were conducted to identify the genes related to WMHs separately in mild cognitive impairment (MCI) and cognitively normal (CN) subjects from the ADNI database. The WMH-related genes identified in patients with MCI were considered to be associated with small-vessel injury in early AD. Functional enrichment analyses and a protein–protein interaction (PPI) network were performed to explore the pathway and hub genes related to the mechanism of small-vessel injury in MCI. Subsequently, the Boruta algorithm and support vector machine recursive feature elimination (SVM-RFE) algorithm were performed to identify feature-selection genes. Finally, the mechanism of small-vessel injury was analyzed in MCI from the immunological perspectives; the relationship of feature-selection genes with various immune cells and neuroimaging indices were also explored. Furthermore, 5×FAD mice were used to demonstrate the genes related to small-vessel injury. The results of the logistic regression analyses suggested that WMHs significantly contributed to MCI, the early stage of AD. A total of 276 genes were determined as WMH-related genes in patients with MCI, while 203 WMH-related genes were obtained in CN patients. Among them, only 15 genes overlapped and were thus identified as the crosstalk genes. By employing the Boruta and SVM-RFE algorithms, CD163, ALDH3B1, MIR22HG, DTX2, FOLR2, ALDH2, and ZNF23 were recognized as the feature-selection genes linked to small-vessel injury in MCI. After considering the results from the PPI network, CD163 was finally determined as the critical WMH-related gene in MCI. The expression of CD163 was correlated with fractional anisotropy (FA) values in regions that are vulnerable to small-vessel injury in AD. The immunostaining and RT-qPCR results from the verifying experiments demonstrated that the indicators of small-vessel injury presented in the cortical tissue of 5×FAD mice and related to the upregulation of CD163 expression. CD163 may be the most pivotal candidates related to small-vessel injury in early AD.

Adipose-derived stem cells (ASCs) possess therapeutic potential for ischemic brain injury, and the chemokine CXCL12 has been shown to enhance their functional properties. However, the cumulative effects of ASCs when combined with various structures of CXCL12 on ischemic stroke and its underlying molecular mechanisms remain unclear. In this study, we genetically engineered mouse adipose-derived ASCs with CXCL12 variants and transplanted them to the infarct region in a mice transient middle cerebral artery occlusion (tMCAO) model of stroke. We subsequently compared the post-ischemic stroke efficacy of ASC-mCXCL12 with ASC-dCXCL12, ASC-wtCXCL12, and unmodified ASCs. Neurobehavior recovery was assessed using modified neurological severity scores, the hanging wire test, and the elevated body swing test. Changes at the tissue level were evaluated through cresyl violet and immunofluorescent staining, while molecular level alterations were examined via Western blot and real-time PCR. The results of the modified neurological severity score and cresyl violet staining indicated that both ASC-mCXCL12 and ASC-dCXCL12 treatment enhanced neurobehavioral recovery and mitigated brain atrophy at the third and fifth weeks post-tMCAO. Additionally, we observed that ASC-mCXCL12 and ASC-dCXCL12 promoted angiogenesis and neurogenesis, accompanied by an increased expression of bFGF and VEGF in the peri-infarct area of the brain. Notably, in the third week after tMCAO, the ASC-mCXCL12 exhibited superior outcomes compared to ASC-dCXCL12. However, when treated with the CXCR4 antagonist AMD3100, the beneficial effects of ASC-mCXCL12 were reversed. The AMD3100-treated group demonstrated worsened neurological function, aggravated edema volume, and brain atrophy. This outcome is likely attributed to the interaction of monomeric CXCL12 with CXCR4, which regulates the recruitment of bFGF and VEGF. This study introduces an innovative approach to enhance the therapeutic potential of ASCs in treating ischemic stroke by genetically engineering them with the monomeric structure of CXCL12.

Chronic kidney disease (CKD) is a public health concern worldwide, and chromium exposure may be a risk factor due to its potential nephrotoxicity. However, research on the association between chromium exposure and kidney function especially the potential threshold effect of chromium exposure is limited. A repeated-measures study involving 183 adults (641 observations) was conducted from 2017 to 2021 in Jinzhou, China. Urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were measured as kidney function biomarkers. Generalized mixed models and two-piecewise linear spline mixed models were used to assess the dose-response relationship and potential threshold effect of chromium on kidney function, respectively. Temporal analysis was conducted by the latent process mixed model to depict the longitudinal change of kidney function over age. Urinary chromium was associated with CKD (odds ratio [OR] = 1.29; 95 % confidence interval [CI], 6.41, 14.06) and UACR (Percent change = 10.16 %; 95 % CI, 6.41 %, 14.06 %), and we did not find significant association between urinary chromium and eGFR (Percent change = 0.06 %; 95 % CI, −0.80 %, 0.95 %). The threshold analyses suggested the existence of threshold effects of urinary chromium, with inflection points at 2.74 μg/L for UACR and 3.95 μg/L for eGFR. Furthermore, we found that chromium exposure exhibited stronger kidney damage over age. Our study provided evidence for the threshold effects of chromium exposure on kidney function biomarkers and the heightened nephrotoxicity of chromium in older adults. More attention should be paid to the supervision of chromium exposure concentrations for preventing kidney damage, especially in older adults.

BackgroundWith the advent of the digital economy and the aging population, the demand for diversified health care services and innovative care delivery models has been overwhelming. This trend has accelerated the urgency to implement effective and efficient data exchange and service interoperability, which underpins coordinated care services among tiered health care institutions, improves the quality of oversight of regulators, and provides vast and comprehensive data collection to support clinical medicine and health economics research, thus improving the overall service quality and patient satisfaction. To meet this demand and facilitate the interoperability of IT systems of stakeholders, after years of preparation, Health Level 7 formally introduced, in 2014, the Fast Healthcare Interoperability Resources (FHIR) standard. It has since continued to evolve. FHIR depends on the Implementation Guide (IG) to ensure feasibility and consistency while developing an interoperable health care service. The IG defines rules with associated documentation on how FHIR resources are used to tackle a particular problem. However, a gap remains between IGs and the process of building actual services because IGs are rules without specifying concrete methods, procedures, or tools. Thus, stakeholders may feel it nontrivial to participate in the ecosystem, giving rise to the need for a more actionable practice guideline (PG) for promoting FHIR’s fast adoption. ObjectiveThis study aimed to propose a general FHIR PG to facilitate stakeholders in the health care ecosystem to understand FHIR and quickly develop interoperable health care services. MethodsWe selected a collection of FHIR-related papers about the latest studies or use cases on designing and building FHIR-based interoperable health care services and tagged each use case as belonging to 1 of the 3 dominant innovation feature groups that are also associated with practice stages, that is, data standardization, data management, and data integration. Next, we reviewed each group’s detailed process and key techniques to build respective care services and collate a complete FHIR PG. Finally, as an example, we arbitrarily selected a use case outside the scope of the reviewed papers and mapped it back to the FHIR PG to demonstrate the effectiveness and generalizability of the PG. ResultsThe FHIR PG includes 2 core elements: one is a practice design that defines the responsibilities of stakeholders and outlines the complete procedure from data to services, and the other is a development architecture for practice design, which lists the available tools for each practice step and provides direct and actionable recommendations. ConclusionsThe FHIR PG can bridge the gap between IGs and the process of building actual services by proposing actionable methods, procedures, and tools. It assists stakeholders in identifying participants’ roles, managing the scope of responsibilities, and developing relevant modules, thus helping promote FHIR-based interoperable health care services.

Abstract Lithium–sulfur (Li‐S) batteries have emerged as one of the most attractive alternatives for post‐lithium‐ion battery energy storage systems, owing to their ultrahigh theoretical energy density. However, the large‐scale application of Li–S batteries remains enormously problematic because of the poor cycling life and safety problems, induced by the low conductivity , severe shuttling effect, poor reaction kinetics, and lithium dendrite formation. In recent studies, catalytic techniques are reported to promote the commercial application of Li–S batteries. Compared with the conventional catalytic sites on host materials, quantum dots (QDs) with ultrafine particle size (

Solar distillation is a sustainable and promising technique to generate fresh water. However, the solar vapor generation is a high energy consumption process, resulting in a low water yield under natural sunlight. Hence, developing of advanced evaporators that can simultaneously reduce the energy requirement of water vaporization and accelerate solar water evaporation remains a great challenge. In this study, we report the fabrication of a multifunctional hydrogel of HxMoO3/PNIPAM with PNIPAM as hydratable skeleton and HxMoO3 as the light-absorbing unit for solar water evaporation. The experimental results demonstrate that the as-prepared hydrogel owns excellent photothermal activity. Accurately, the fabricated hydrogel -based solar evaporators achieved high water evaporation rate of 1.65 kg m−2 h−1 with the energy conversion efficiency of 85.87% under 1 kW m−2 irradiation. The enhanced photothermal activity of HxMoO3/PNIPAM hydrogel can be attributed to the synergistic effects of the components composed in this hierarchical architecture that change the water state and further speed up water evaporation. The HxMoO3/PNIPAM evaporators indicate its great potential for practical implementation of solar water evaporation.

Combining the physical advantages of two-dimensional (2D) inorganic nanosheets and the modular design and programmed structure of metal-organic frameworks (MOFs), 2D MOFs remain at the forefront of functional material research. Despite tremendous efforts, precise control in the synthesis of 2D nonlayered MOFs with predesigned topology for desired applications remains challenging. Success in the bottom-up synthesis of 2D nonlayered MOFs via ligand exchange motivated us to incorporate partial BTC (BTC = 1,3,5-benzenetricarboxylate) ligand dissociation and CO2 capped coordination into the top-down treatment of bulk Cu-BTC MOF, leading to successful conversion of a 3D nonlayered network to a 2D Cu-based topological structure. Notably, a supercritical CO2-containing solvent mixture is employed to provide the desired defect and coordination engineering. Thus, our work introduces a new top-down concept based on modulated synthesis to fabricate high-quality 2D nonlayered MOFs for the first time.

Abstract High‐energy‐density lithium metal batteries (LMBs) are widely accepted as promising next‐generation energy storage systems. However, the safety features of practical LMBs are rarely explored quantitatively. Herein, the thermal runaway behaviors of a 3.26 Ah (343 Wh kg−1) Li | LiNi0.5Co0.2Mn0.3O2 pouch cell in the whole life cycle are quantitatively investigated by extended volume‐accelerating rate calorimetry and differential scanning calorimetry. By thermal failure analyses on pristine cell with fresh Li metal, activated cell with once plated dendrites, and 20‐cycled cell with large quantities of dendrites and dead Li, dendrite‐accelerated thermal runaway mechanisms including reaction sequence and heat release contribution are reached. Suppressing dendrite growth and reducing the reactivity between Li metal anode and electrolyte at high temperature are effective strategies to enhance the safety performance of LMBs. These findings can largely enhance the understanding on the thermal runaway behaviors of Li metal pouch cells in practical working conditions.

Objective To investigate the serological and molecular genetic characteristics of B(A) and cisAB blood groups discovered in our laboratory. Methods ABO blood group serology and genetic tests were used to identify blood groups of 6 blood samples, submitted by blood center and hospitals in Shandong, and pedigree investigation was carried on 2 of them. Results Among the 6 samples, serological results were B(A) in 5 cases and cisAB in 1 case. The results of genetic tests were consistent with the serological results, as the alleles included B(A)04, B(A)02 and cisAB01, and all genotypes were heterozygous with O. Serological pedigree study was conducted on 2 samples: One cisAB patient with his 4 relatives(cisAB type father and three O type relatives) and one B(A)02/O1 donor with his 3 relatives[ B(A) type father/brother and O type mother). For B(A)02/O1 donor, the results of genetic testing were consistent with the serological results, as the paternal genotype was the same as that of the proband, the younger brother was B(A)02/O2, and the maternal genotype was O1/O2. Conclusion The cisAB and B(A) blood groups are often indistinguishable by serological phenotypes and require genetic confirmation. CisAB pedigree investigation revealed 2 cases of cisAB blood type and B(A) pedigree investigation revealed 3 cases of B(A). The genotyping of cisAB and B(A) in this region were cisAB01/O2, B(A)02/O1, B(A)02/O2, B(A)04/O1 and B(A)04/O2. B(A)and cisAB subtypes can be accurately identified through genetic testing and pedigree investigation, which can provide a reliable basis for blood transfusion selection and ensure the safety of clinical blood transfusion.

Lipidemic effect of air pollutants are still inconsistent and their joint effects are neglected. Meanwhile, identified inflammation pathways in animal have not been applied in epidemiological studies, and beneficial effect of residential greenness remained unclear. Therefore, we used data from typically air-polluted Chinese cities to answer these questions. Particulate matter (PM) with a diameter of ≤ 1 µm (PM1), PM with a diameter of ≤ 2.5 µm (PM2.5), PM with a diameter of ≤ 10 µm (PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) were predicted by space–time extremely randomized trees model. Residential greenness was reflected by Normalized Difference Vegetation Index (NDVI). Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured, and atherogenic coefficient (AC) and TG/HDL-C (TGH) ratio were calculated to indicate lipid metabolism. Generalized additive mixed model and quantile g-computation were respectively conducted to investigate individual and joint lipidemic effect of air pollutants. Covariates including demographical characteristics, living habits, meteorological factors, time trends, and disease information were considered to avoid confounding our results. Complement C3 and high-sensitivity C-reactive protein (hsCRP) were analyzed as potential mediators. Finally, association between NDVI and lipid markers were explored. We found that long-term air pollutants exposure were positively associated with lipid markers. Complement C3 mediated 54.72% (95% CI: 0.30, 63.10) and 72.53% (95% CI: 0.65, 77.61) of the association between PM1 and TC and LDL-C, respectively. We found some significant associations of lipid markers with NDVI1000 m rather than NDVI500 m. BMI, disease status, smoke/drink habits are important effect modifiers. Results are robust in sensitive analysis. Our study indicated that air pollutants exposure may detriment lipid metabolism and inflammation may be the potential triggering pathways, while greenness may exert beneficial effects. This study provided insights for the lipidemic effects of air pollution and greenness.

Milling and appearance quality are important contributors to rice grain quality. Abundant genetic diversity and a suitable environment are crucial for rice improvement. In this study, we investigated the milling and appearance quality-related traits in a panel of 200 japonica rice cultivars selected from Liaoning, Jilin and Heilongjiang provinces in Northeast China. Pedigree assessment and genetic diversity analysis indicated that cultivars from Jilin harbored the highest genetic diversity among the three geographic regions. An evaluation of grain quality indicated that cultivars from Liaoning showed superior milling quality, whereas cultivars from Heilongjiang tended to exhibit superior appearance quality. Single- and multi-locus genome-wide association studies (GWAS) were conducted to identify loci associated with milling and appearance quality-related traits. Ninety-nine significant single-nucleotide polymorphisms (SNPs) were detected. Three common SNPs were detected using the mixed linear model (MLM), mrMLM, and FASTmrMLM methods. Linkage disequilibrium decay was estimated and indicated three candidate regions (qBRR-1, qBRR-9 and qDEC-3) for further candidate gene analysis. More than 300 genes were located in these candidate regions. Gene Ontology (GO) analysis was performed to discover the potential candidate genes. Genetic diversity analysis of the candidate regions revealed that qBRR-9 may have been subject to strong selection during breeding. These results provide information that will be valuable for the improvement of grain quality in rice breeding.

BackgroundThis study explored the mediating role of glucose homeostasis indicators in the relationship between serum cystatin C and mild cognitive impairment (MCI).MethodsThe present study used a cross-sectional design and included 514 participants aged ≥50 years in Beijing, China. The Mini-Mental State Examination was used to assess cognitive function. Serum cystatin C and a comprehensive set of glucose homeostasis indicators were detected, including fasting blood glucose (FBG), glycosylated albumin percentage (GAP), glycated hemoglobin (HbAlc), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-β). Generalized linear models were used to investigate the associations among cystatin C, glucose homeostasis indicators, and cognitive function. Mediation analysis was conducted to explore potential mediator variables.ResultsIn this study of 514 participants, 76 (14.8%) had MCI. Those with cystatin C levels ≥1.09 mg/L had a 1.98-fold higher risk of MCI than those with levels

Sequencing technology is the most commonly used technology in molecular biology research and an essential pillar for the development and applications of molecular biology. Since 1977, when the first generation of sequencing technology opened the door to interpreting the genetic code, sequencing technology has been developing for three generations. It has applications in all aspects of life and scientific research, such as disease diagnosis, drug target discovery, pathological research, species protection, and SARS-CoV-2 detection. However, the first- and second-generation sequencing technology relied on fluorescence detection systems and DNA polymerization enzyme systems, which increased the cost of sequencing technology and limited its scope of applications. The third-generation sequencing technology performs PCR-free and single-molecule sequencing, but it still depends on the fluorescence detection device. To break through these limitations, researchers have made arduous efforts to develop a new advanced portable sequencing technology represented by nanopore sequencing. Nanopore technology has the advantages of small size and convenient portability, independent of biochemical reagents, and direct reading using physical methods. This paper reviews the research and development process of nanopore sequencing technology (NST) from the laboratory to commercially viable tools; discusses the main types of nanopore sequencing technologies and their various applications in solving a wide range of real-world problems. In addition, the paper collates the analysis tools necessary for performing different processing tasks in nanopore sequencing. Finally, we highlight the challenges of NST and its future research and application directions.

BackgroundLungs were initially thought to be sterile. However, with the development of sequencing technologies, various commensal microorganisms, especially bacteria, have been observed in the lungs of healthy humans. Several studies have also linked lung microbes to infectious lung diseases. However, few databases have focused on the metagenomics of lungs to provide microbial compositions and corresponding metadata information. Such a database would be handy for researching and treating lung diseases.MethodsTo provide researchers with a preliminary understanding of lung microbes and their research methods, the LDMD collated nearly 10,000 studies in the literature covering over 30 diseases, gathered basic information such as the sources of lung microbe samples, sequencing methods, and processing software, as well as analyzed the metagenomic sequencing characteristics of lung microbes. Besides, the LDMD also contained data collected in our laboratory.ResultsIn this study, we established the Lung Disease Microorganisms Database (LDMD), a comprehensive database of microbes involved in lung disease. The LDMD offered sequence analysis capabilities, allowing users to upload their sequencing results, align them with the data collated in the database, and visually analyze the results.ConclusionIn conclusion, the LDMD possesses various functionalities that provide a convenient and comprehensive resource to study the lung metagenome and treat lung diseases.

Introduction: Previous studies have reported that chromium (Cr)-induced epigenetic alterations and DNA methylation play a vital role in the pathogenesis of diseases induced by chromium exposure. Epigenomic analyses have been limited and mainly focused on occupational chromium exposure; their findings are not generalizable to populations with environmental Cr exposure.Methods: We identified the differential methylation of genes and regions to elucidate the mechanisms of toxicity related to environmental chromium exposure. DNA methylation was measured in blood samples collected from individuals in Cr-contaminated (n = 10) and unexposed areas (n = 10) by using the Illumina Infinium HumanMethylation850K array. To evaluate the relationship between chromium levels in urine and CpG methylation at 850 thousand sites, we investigated differentially methylated positions (DMPs) and differentially methylated regions (DMRs) by using linear models and DMRcate method, respectively. The model was adjusted for biologically relevant variables and estimated cell-type compositions.Results: At the epigenome-wide level, we identified five CpGs [cg20690919 (pFDR =0.006), cg00704664 (pFDR =0.024), cg10809143 (pFDR =0.043), cg27057652 (pFDR =0.047), cg05390480 (pFDR =0.024)] and one DMR (chr17: 19,648,718-19,648,972), annotated to ALDH3A1 genes (p < 0.05) as being significantly associated with log2 transformed urinary chromium levels.Discussion: Environmental chromium exposure is associated with DNA methylation, and the significant DMPs and DMR being annotated to cause DNA damage and genomic instability were found in this work. Research involving larger samples is required to further explore the epigenetic effect of environmental chromium exposure on health outcomes through DNA methylation.

Dyslipidemia is a common disease in the older population and represents a considerable disease burden worldwide. Epidemiological and experimental studies have indicated associations between heavy metal exposure and dyslipidemia; few studies have investigated the effects of heavy metal mixture and interactions between metals on dyslipidemia. We recruited 1121 participants living in heavy metal–contaminated and control areas in northeast China from a cross-sectional survey (2017–2019). Urinary metals including chromium (Cr), cadmium (Cd), lead (Pb), and manganese (Mn) and dyslipidemia biomarkers, namely triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels, were measured. The generalized linear model (GLM) was used to explore the association of a single metal with dyslipidemia biomarkers. Bayesian kernel machine regression (BKMR) and multivariable linear regression were performed to explore the overall effect of metal mixture and the interaction between metals on dyslipidemia. Heavy metal mixture was positively associated with LDL-C, TC, and TG and negatively with HDL-C. In multivariable linear regression, Pb and Cd exhibited a synergistic association with LDL-C in the participants without hyperlipemia. Mn-Cd and Pb-Cr also showed a synergistic association with increasing the level of LDL-C in subjects without hyperlipemia. Cd-Cr showed an antagonistic association with HDL-C, respectively. Cr-Mn exhibited an antagonistic association with decreased HDL-C and TG levels. No significant interaction was noted among the three metals. Our study indicated that exposure to heavy metals is associated with dyslipidemia biomarkers and the presence of potential synergistic or antagonistic interactions between the heavy metals.

Aiming at the high-dimensional uncertainties of restoration process, an optimization model for distribution system restoration control is proposed considering expected restoration benefits, expected restoration costs, and security risks of the overall restoration scheme. In the proposed model, the effect of security control on restoration process is actively analyzed considering the security control costs of preventive, emergency, and correction controls. A two-layer decision support framework for distribution system restoration decision support system (DRDSS) is also designed. The upper layer of the proposed framework generates the pre-adjustment schemes of operation mode for energized power grid by load transfer and selects the optimal pre-adjustment scheme and the corresponding partitioning scheme based on the partition adjustment results of each pre-adjustment scheme. In addition, it optimizes the spatial-temporal decision-making of the inter-partition connectivity. For each partition, the lower layer of the proposed framework pre-selects the units and loads to be restored according to the pre-evaluated restoration income, generates the table of alternative restoration scheme for coping with uncertain events through simulation and deduction, and evaluates the risk and benefit of each scheme. For the uncertain events in the actual restoration process, the current restoration scheme can be adaptively switched to a sub-optimal scheme or re-optimized if necessary. Meanwhile, the proposed framework provides an information interaction interface for collaborative restoration with the related transmission system. A 123-node test system is built to evaluate the effectiveness and adaptability of the proposed model and framework.