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Abstract Deconvolution is an efficient approach for detecting cell-type-specific (cs) transcriptomic signals without cellular segmentation. However, this type of methods may require a reference profile from the same molecular source and tissue type. Here, we present a method to dissect bulk proteome by leveraging tissue-matched transcriptome and proteome without using a proteomics reference panel. Our method also selects the proteins contributing to the cellular heterogeneity shared between bulk transcriptome and proteome. The deconvoluted result enables downstream analyses such as cs-protein Quantitative Trait Loci (cspQTL) mapping. We benchmarked the performance of this multimodal deconvolution approach through CITE-seq pseudo bulk data, a simulation study, and the bulk multi-omics data from human brain normal tissues and breast cancer tumors, individually, showing robust and accurate cell abundance quantification across different datasets. This algorithm is implemented in a tool MICSQTL that also provides cspQTL and multi-omics integrative visualization, available at https://bioconductor.org/packages/MICSQTL .

BackgroundKaposiform hemangioendothelioma (KHE) is a rare vascular tumor with a high risk of mortality. Few studies with large samples of KHE have been reported. KHE may develop into the Kasabach–Merritt phenomenon (KMP), which is characterized by thrombocytopenia and consumptive coagulopathy. The features of severe symptomatic anemia and life-threatening low platelets make the management of KHE associated with KMP challenging.ObjectiveThe aim of this study was to examine the clinical characteristics of patients with KHE and discuss the treatment experience for different risk groups of KHE.MethodsThrough a retrospective review of 70 patients diagnosed with KHE between 2017 and 2022 in our center, we classify lesions into three clinicopathological stages based on the tumor involving depth, and divided the severity of KHE into three levels by estimating clinicopathological stages and severity of thrombocytopenia. Treatments of different severity groups were estimated with sufficient data.ResultsIn our cohort, 27% were neonates, and KHE lesion occurred at birth in 84% of patients. There was a slight male predominance (32 girls and 38 boys). Common clinical characteristics included associated coagulation disorder (100%), locally aggressive cutaneous blue–purple mass (89%), thrombocytopenia (78%), and local pain or joint dysfunction (20%). The lower extremities were the dominant location (35%), followed by the trunk (29%), the maxillofacial region and neck (24%), and the upper extremities (10%). Of the total cohort, 78% developed KMP; the median age at which thrombocytopenia occurred was 27.8 days. The median platelet count of patients who were associated with KMP was 24,000/µL in our cohort. Ninety-two percent of patients were given surgery treatment and 89% of these patients were given high-dose methylprednisolone (5-6 mg/kg daily) before surgery. In 55 patients with KMP, 36% were sensitive to high-dose corticosteroid therapy. Patients from the low-risk group (eight cases) underwent operation, all of whom recovered without recurrence after a maximum follow-up of 5 years. Out of 26 patients from the high-risk group, 25 underwent surgery treatment, with 1 case undergoing secondary surgery after recurrence and 1 case taking sirolimus. Out of 36 cases from the extremely high-risk group, 32 underwent surgery (including 2 cases who underwent external carotid artery ligation and catheterization), 3 of whom underwent secondary operation after recurrence, and the remaining 4 cases took medicine. The mean length of having sirolimus was 21 months; two cases stopped taking sirolimus due to severe pneumonia. Two cases died at 1 and 3 months after discharge.ConclusionsOur study describes the largest assessment of high-risk patients with KHE who have undergone an operation to date, with 5 years of follow-up to track recovery, which provides invaluable knowledge for the future treatment of patients with KHE and KMP from different risk groups: Early surgical intervention may be the most definitive treatment option for most patients with KHE; multimodality treatment is the best choice for the extremely high-risk group.

Abstract Molecular-glue degraders are small molecules that induce a specific interaction between an E3 ligase and a target protein, resulting in the target proteolysis. The discovery of molecular glue degraders currently relies mostly on screening approaches. Here, we describe screening of a library of cereblon (CRBN) ligands against a panel of patient-derived cancer cell lines, leading to the discovery of SJ7095, a potent degrader of CK1α, IKZF1 and IKZF3 proteins. Through a structure-informed exploration of structure activity relationship (SAR) around this small molecule we develop SJ3149, a selective and potent degrader of CK1α protein in vitro and in vivo. The structure of SJ3149 co-crystalized in complex with CK1α + CRBN + DDB1 provides a rationale for the improved degradation properties of this compound. In a panel of 115 cancer cell lines SJ3149 displays a broad antiproliferative activity profile, which shows statistically significant correlation with MDM2 inhibitor Nutlin-3a. These findings suggest potential utility of selective CK1α degraders for treatment of hematological cancers and solid tumors.

The analytical solution of distributed water table in an unconfined aquifer between streams has been obtained in classic groundwater hydraulics based on Dupuit’s assumption, and it is frequently used in engineering practice. However, the applicability of this analytical model to groundwater in karst fractures needs a further verification. A 2D profile model of discrete fractures in rockmass between streams with equal water levels was simulated, considering a rainfall infiltration rate of 100−800 mm/a. The random fracture network includes two fracture groups, steeply or slightly inclining with the same statistic average aperture of 0.01 cm. Phreatic surface were identified by checking the interface between saturated and unsaturated fractures. The equivalent hydraulic conductivity of saturated fractures was obtained from seepage simulations and compared to the inversely estimated result from the classical analytical solution. It indicates that the relative error of inverse estimation is smaller than 25%. Further, the change in fractures aperture due to dissolution of Karst rocks was simulated with predictions on the state of fractures and quasi-steady state seepage in a 10 ka period. It finds that the maximum of the fracture aperture reaches 0.07 cm, and the classical model can yield an equivalent hydraulic conductivity from water table distribution with the same order of magnitude as the real hydraulic conductivity. The simulation shows an irregular shape of water table and seepage springs on river sides, where the number of springs reduced gradually following the karstification process. Though the classical analytical model can be used to estimate the equivalent hydraulic conductivity of the fractured aquifer between streams, it is unable to reveal the irregular water table shape and predict the change in seepage in Karst fractures.

Abstract Norepinephrine (NA), a stress hormone, can accelerate hair graying by binding to β2 adrenergic receptors (β2AR) on melanocyte stem cells (McSCs). From this, NA-β2AR axis could be a potential target for preventing the stress effect. However, identifying selective blockers for β2AR has been a key challenge. Therefore, in this study, advanced computer-aided drug design (CADD) techniques were harnessed to screen natural molecules, leading to the discovery of rhynchophylline as a promising compound. Rhynchophylline exhibited strong and stable binding within the active site of β2AR, as verified by molecular docking and dynamic simulation assays. When administered to cells, rhynchophylline effectively inhibited NA-β2AR signaling. This intervention resulted in a significant reduction of hair graying in a stress-induced mouse model, from 28.5% to 8.2%. To gain a deeper understanding of the underlying mechanisms, transcriptome sequencing was employed, which revealed that NA might disrupt melanogenesis by affecting intracellular calcium balance and promoting cell apoptosis. Importantly, rhynchophylline acted as a potent inhibitor of these downstream pathways. In conclusion, the study demonstrated that rhynchophylline has the potential to mitigate the negative impact of NA on melanogenesis by targeting β2AR, thus offering a promising solution for preventing stress-induced hair graying. Graphical Abstract

Microplastics (MPs) are pervasive pollutants in the natural environment and contribute to increased levels of illness in both animals and humans. However, the specific impacts of MPs on skin damage and alopecia are not yet well understood. In this study, we have examined the effects of two types of polystyrene MPs (pristine and aged) on skin and hair follicle damage in mice. UV irradiation changed the chemical and physical properties of the aged MPs, including functional groups, surface roughness, and contact angles. In both in vivo and in vitro experiments, skin and cell injuries related to oxidative stress, apoptosis, tight junctions (TJs), alopecia, mitochondrial dysfunction, and other damages were observed. Mechanistically, MPs and aged MPs can induce TJs damage via the oxidative stress pathway and inhibition of antioxidant-related proteins, and this can lead to alopecia. The regulation of cell apoptosis was also observed, and this is involved in the ROS-mediated mitochondrial signaling pathway. Importantly, aged MPs showed exacerbated toxicity, which may be due to their elevated surface irregularities and altered chemical compositions. Collectively, this study suggests a potential therapeutic approach for alopecia and hair follicle damage caused by MPs pollution.

Abstract Ubiquitination is a post-translational modification initiated by the E1 enzyme UBA1, which transfers ubiquitin to ~35 E2 ubiquitin-conjugating enzymes. While UBA1 loss is cell lethal, it remains unknown how partial reduction in UBA1 activity is endured. Here, we utilize deep-coverage mass spectrometry to define the E1-E2 interactome and to determine the proteins that are modulated by knockdown of UBA1 and of each E2 in human cells. These analyses define the UBA1/E2-sensitive proteome and the E2 specificity in protein modulation. Interestingly, profound adaptations in peroxisomes and other organelles are triggered by decreased ubiquitination. While the cargo receptor PEX5 depends on its mono-ubiquitination for binding to peroxisomal proteins and importing them into peroxisomes, we find that UBA1/E2 knockdown induces the compensatory upregulation of other PEX proteins necessary for PEX5 docking to the peroxisomal membrane. Altogether, this study defines a homeostatic mechanism that sustains peroxisomal protein import in cells with decreased ubiquitination capacity.

Traditional horizontal-axis wind turbines (HAWTs) have limited efficiency in low-wind speed regions. In this paper, an integrated energy system (IES) incorporating vertical-axis wind turbines (VAWTs) is proposed; this IES is located in an oilfield management area, which can utilize the low-wind speed resources more efficiently and improve renewable energy consumption, and it also introduces a demand response model based on thermal inertia (TI), thus smoothing out the volatility caused by the VAWT. Typical output scenarios are obtained through stochastic optimization to deal with wind turbine and photovoltaic output uncertainties, and an optimal scheduling model is proposed to minimize the system operating cost. Finally, a simulation study was conducted in a micro-oilfield management area in Shandong Province, China, to demonstrate the performance of the proposed system. The results show that the IES using a VAWT and TI can increase the renewable energy consumption capacity by 87% over the conventional HAWT system, change the user behavior, increase the economic efficiency by 12%, and achieve the smoothing of load-side fluctuation of electric and thermal loads, peak shaving, and valley filling. This paper provides a feasible solution for an IES in low-wind speed areas.

Objective The Dupuit model of well flow is a classical steady-state well flow model for a homogeneous unconfined aquifer in a round island. However, it does not consider the widely existing infiltration recharge from precipitation, and is also inapplicable for stratified heterogeneous aquifer systems. Therefore, it must be modified to address these issues. Methods On the basis of the revised Dupuit well flow model which incorporates infiltration recharge, this study further extended its application to a stratified heterogeneous unconfined aquifer. The Girinskii's potential function was used to construct the differential equations for the radial groundwater flow according to the water balance principle, and the analytical solutions satisfying the boundary conditions are then obtained as formulas of the flow rate, water table and groundwater divide. Taking the bilayer structure as an example, typical groundwater level curves with respect to 30 scenarios of different parameter values were investigated. A special phenomenon was found in which the curves of different hydraulic conductivities intersect at a single point, which could also be proven in theory. This analytical model still adopted the Dupuit assumption and did not consider the "hydraulic jump" phenomenon on the wall of the pumping well. To check the impact of these constraints on the applicability of the analytical formulas, a two-dimensional numerical model for axially symmetric seepage was built for comparison. Results As indicated by the results, the relative error of the groundwater level estimated from the analytical solution is generally less than 4%, except for the zone near the pumping well. On the groundwater divide, where the Dupuit assumption is mostly invalid, the relative errors of the analytical solution to both the distance and height of the divide are smaller than 0.1%. Conclusion The Dupuit assumption does not significantly influence applicability of the analytical model.

Significance Prof. Chongxi Chen has long been engaged in teaching courses, personnel training and scientific research in the field of hydrogeology, working diligently and innovatively, and has achieved fruitful academic research results. Progress This article makes a systematic review of Prof. Chongxi Chen's academic contributions in the field of hydrogeology, mainly including three aspects: ① Carrying out innovative and theoretical researchon groundwater hydraulics. He corrected the historical model error of "steady-state well flow within the influence radius", developed a series of analytical models for special hydrogeological problems, and improved and extended classical well flow models. ② Continuously exploring hydrogeological simulation methods. He proposed a number of techniques and methods to improve the emulational level of groundwater simulation, such as the equivalent submarine discharge boundary of coastal groundwater, the coupling seepage-pipe flow model, the linear-nonlinear flow model in triple Karst media of cave-fracture-porous and the groundwater withdrawal-land subsidence model, etc. He also developed a unique and advantageous software for groundwater flow simulation, PGMS. ③ Proposing a theory of recharge-discharge changes for the evaluation of the sustainable groundwater extraction. He completed groundwater modelling in several typical regions in China, which played a demonstration role for the scientific assessment of groundwater resources. Conclusions and Prospects Prof. Chongxi Chen's innovative research has played an important role in promoting the development of hydrogeology in China.

Objective Pumping tests are an important method for determining the hydrogeological parameters of aquifers and evaluating groundwater resources. For the analysis of single-well pumping tests, existing models assume that the well diameter remains constant with depth and that the aquifer is either unconfined or confined. They do not consider situations where the well diameter varies or when multiple aquifers are encountered. Methods In this study, we developed a steady-state mixed-well flow model to account for a pumping well with a variable diameter that penetrates multiple aquifers with the assumption of horizontal flow within the aquifers. The analytical solutions for the relation between pumping discharge and drawdown were derived. This study explores the methodology of using single-well steady-state pumping tests with variable-diameter wells to obtain aquifer parameters. Additionally, accurate solutions for the equivalent radius of a confined aquifer segment and alternative radius calculation formulas are proposed. Results The mixed-well flow model was applied to analyze pumping tests near the Zihe River. Based on the data from three stepped pumping tests, a parabolic relationship between pumping discharge Qw and drawdown sw was established.The model predicted a pumping discharge of 4 093.8 m3/d when the maximum drawdown sw was 25 m. The hydraulic conductivity of the unconfined aquifer was estimated to be 1.88 m/d, and the hydraulic conductivity of the confined aquifer was estimated as 0.43 m/d, with a relative error of less than 5%. Conclusion The mixed-well model serves as a theoretical foundation for predicting water yield from pumping wells in multiple aquifers system. However, it is important to acknowledge that the model's applicability is constrained by certain assumptions. In situations where rivers fully penetrate aquifers, there is a possibility of overestimating the hydraulic conductivity. On the other hand, when rivers only partially penetrate aquifers, the analytical solution may underestimate the hydraulic conductivity.

Objective Both the classical Dupuit model and the modified Dupuit model including infiltration are influenced by Dupuit's assumption and have potential systematic errors. Building a numerical model of well flow in an unconfined aquifer by characterizing the three-dimensional or axisymmetric two-dimensional (2D) flow is an essential approach to verify the performance of Dupuit-type models. Methods In this study, a 2D numerical model is proposed for the steady state well-flow in an unconfined aquifer, in which the control equation of seepage in the cylindrical coordinates is transformed equivalently to the Cartesian coordinates through parameter transformation, and the sectional 2D modelling is implemented via the MODFLOW finite-difference grid of cubic blocks. In the numeric model, the water level in the pumping well is a given condition, the flux across the seepage face is estimated by difference equation according to Darcy's law, the phreatic surface is identified by the treatment of dry and wet cells in MODFLOW, and the pumping rate is determined from the water debug calculation. Results Fine grids are constructed innumerical models of typical cases to obtain high-precision results, in which the relative error of the backwards estimated pumping rate is no more than 0.2%. This numerical model is used to check the Dupuit-type well-flow models. As indicated, the groundwater level estimated from the analytical formulas generally agrees well with the numerical modelling results, except that near the well, where the analytical solution underestimates the groundwater level due to ignoring the waterjump and the errors depend on the anisotropic permeability of the aquifer. When infiltration exists, the flow in the vicinity of watershed does not follow Dupuit's assumption. However, the estimated groundwater level on the watershed by modified Dupuit well-flow equation has a low level of relative error, which is less than 1%. Conclusion This numerical method is simple and practical however it is also influenced by limitations in MODFLOW.

Significance Groundwater flow paths may cross the surface divide at the regional scale, resulting in interbasin groundwater circulation that affects hydrological relationships and solute transport process between basins. However, research on interbasin groundwater circulation is still in its infancy internationally, and the progress achieved is a matter of concern. Progress This study systematically tracks and analyses the literature on interbasin groundwater circulation at home and abroad in the past 20 years and summarizes the existing research progress from three perspectives: formation mechanism, identification methods, and impact assessment. In terms of the hydrodynamic formation mechanism, the study theoretically determines the deviation characteristics between the surface divide, the highest point of the water table and the divide point of groundwater flow systems. Based on the deviation characteristics, multiple interbasin groundwater circulation paths can be separated between rivers.In terms of identifying the interbasin groundwater circulation, a series of real basin cases provide available methods, including the water balance method, basin-scale hydrological model and hydrogeochemical end element mixed model. The methods identify the existence of interbasin groundwater circulation and even evaluate the circulation fluxes, which can improve the recognition of the water balance in the basin. It is also found that the location, size, climate and geological conditions of the basin affect the occurrence and flux of interbasin groundwater circulation.In terms of impact assessment, it is preliminarily found that the interbasin groundwater circulation has an important impact on the assessments of climate sensitivity, state parameters of the Budyko framework and carbon source/sink in the basin. Ignoring its role may lead to obviously incorrect conclusions. Conclusions and Prospects At present, research on the dynamic process and material transport effect of interbasin groundwater circulation is relatively weak. Accurate and quantitative evaluation methods are also lacking. The focuses of future research are to reveal the circulation paths of interbasin groundwater in three-dimensional aquifer space and accurately assess the various impacts of interbasin groundwater circulation.

Arterial blood pressure (ABP) serves as a pivotal clinical metric in cardiovascular health assessments, with the precise forecasting of continuous blood pressure assuming a critical role in both preventing and treating cardiovascular diseases. This study proposes a novel continuous non-invasive blood pressure prediction model, DSRUnet, based on deep sparse residual U-net combined with improved SE skip connections, which aim to enhance the accuracy of using photoplethysmography (PPG) signals for continuous blood pressure prediction. The model first introduces a sparse residual connection approach for path contraction and expansion, facilitating richer information fusion and feature expansion to better capture subtle variations in the original PPG signals, thereby enhancing the network’s representational capacity and predictive performance and mitigating potential degradation in the network performance. Furthermore, an enhanced SE-GRU module was embedded in the skip connections to model and weight global information using an attention mechanism, capturing the temporal features of the PPG pulse signals through GRU layers to improve the quality of the transferred feature information and reduce redundant feature learning. Finally, a deep supervision mechanism was incorporated into the decoder module to guide the lower-level network to learn effective feature representations, alleviating the problem of gradient vanishing and facilitating effective training of the network. The proposed DSRUnet model was trained and tested on the publicly available UCI-BP dataset, with the average absolute errors for predicting systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) being 3.36 ± 6.61 mmHg, 2.35 ± 4.54 mmHg, and 2.21 ± 4.36 mmHg, respectively, meeting the standards set by the Association for the Advancement of Medical Instrumentation (AAMI), and achieving Grade A according to the British Hypertension Society (BHS) Standard for SBP and DBP predictions. Through ablation experiments and comparisons with other state-of-the-art methods, the effectiveness of DSRUnet in blood pressure prediction tasks, particularly for SBP, which generally yields poor prediction results, was significantly higher. The experimental results demonstrate that the DSRUnet model can accurately utilize PPG signals for real-time continuous blood pressure prediction and obtain high-quality and high-precision blood pressure prediction waveforms. Due to its non-invasiveness, continuity, and clinical relevance, the model may have significant implications for clinical applications in hospitals and research on wearable devices in daily life.

The hydrogen and oxygen isotopes in precipitation have the altitude effect, and they participate in the groundwater circulation after the infiltration of precipitation. How does the altitude effect of hydrogen and oxygen isotopes in precipitation transform to the depth effect of hydrogen and oxygen isotopes in groundwater under the influence of groundwater flow systems? The existing research lacks quantification for this problem. In this study, the steady-state groundwater flow theoretical models represented by unidirectional inclined basin and bimodal wavy basin are constructed. The MODFLOW and MT3DMS programs are used to simulate the two-dimensional groundwater flow field in the profile and the convection-dispersion process of heavy isotope molecules to obtain the spatial distribution of D and 18O values in groundwater and discuss the mechanism of altitude effect of the hydrogen and oxygen isotopes transforming to depth effect in the groundwater flow systems. The results indicate that in the monoclinal basin, the altitude effect of D and 18O content in precipitation in the recharge area is transformed to the depth effect of δD and δ18O values in groundwater through the regional groundwater flow system which exponentially decreases with the increasing water table depth in the drainage area. In the bimodal wavy basin, when the permeability of the aquifer is relatively larger than the infiltration intensity (K0/w=1000), only one regional groundwater flow system develops, and the distribution of δD and δ18O presents a S-shaped curve with the increasing water table depth in the discharge area of regional groundwater. When the permeability of the aquifer is relatively smaller than the infiltration intensity (K0/w=250), multiple local groundwater flow systems develop in the bimodal wavy basin. The δD and δ18O indicate an S-shaped curve with the increasing water table depth in the discharge area of regional groundwater, while in the discharge area of local groundwater, they show a monotonic attenuation trend with the increasing water table depth. This study theoretically advances the understanding of the influence mechanism of groundwater flow systems on solute transport, and reveals the indicative role of hydrogen and oxygen isotopes in groundwater flow systems.

Hair follicle (HF) homeostasis is regulated by various signaling pathways. Disruption of such homeostasis leads to HF disorders, such as alopecia, pigment loss, and hair aging, which is causing severe health problems and aesthetic concerns. Among these disorders, hair aging is characterized by hair graying, hair loss, hair follicle miniaturization (HFM), and structural changes to the hair shaft. Hair aging occurs under physiological conditions, while premature hair aging is often associated with certain pathological conditions. Numerous investigations have been made to determine the mechanisms and explore treatments to prevent hair aging. The most well-known hypotheses about hair aging include oxidative stress, hormonal disorders, inflammation, as well as DNA damage and repair defects. Ultimately, these factors pose threats to HF cells, especially stem cells such as hair follicle stem cells, melanocyte stem cells, and mesenchymal stem cells, which hamper hair regeneration and pigmentation. Here, we summarize previous studies investigating the above mechanisms and the existing therapeutic methods for hair aging. We also provide insights into hair aging research and discuss the limitations and outlook.

This study aimed to extract tiger nut polysaccharides (TNPs) by the cellulase method which were graded using the DEAE-cellulose ion exchange method to obtain neutral (TNP-N) and acidic (TNP-A) polysaccharide classes. Analysis of the physical structures and monosaccharide compositions of TNP-A (3.458 KDa) and TNP-N (10.640 KDa) revealed lamellar and dense flocculent structures, with both primarily containing the monosaccharides glucose, galactose, and arabinose (Glc, Gal, and Ara). Single-factor and orthogonal tests were used to select three hydrocolloids, and the optimal ratio of the composite hydrocolloids was determined. Peanut protein drinks with a centrifugal sedimentation rate of 9.71% and a stability factor of 69.28% were obtained by adding 2.78% polysaccharide extract, 0.1% monoglyceride, and peanut pulp at a ratio of 1:15.5 g/mL. Polysaccharide protein drinks are more stable than commercially available protein drinks, with nutritional parameters either comparable to or better than those of the non-polysaccharide protein drinks.

Many metastatic cancers with poor prognoses correlate to downregulated CD82, but exceptions exist. Understanding the context of this correlation is essential to CD82 as a prognostic biomarker and therapeutic target. Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancer. We aimed to uncover the function and mechanism of CD82 in OSCC. We investigated CD82 in human OSCC cell lines, tissues, and healthy controls using the CRISPR-Cas9 gene knockout, transcriptomics, proteomics, etc. CD82 expression is elevated in CAL 27 cells. Knockout CD82 altered over 300 genes and proteins and inhibited cell migration. Furthermore, CD82 expression correlates with S100 proteins in CAL 27, CD82KO, SCC-25, and S-G cells and some OSCC tissues. The 37–50 kDa CD82 protein in CAL 27 cells is upregulated, glycosylated, and truncated. CD82 correlates with S100 proteins and may regulate their expression and cell migration. The truncated CD82 explains the invasive metastasis and poor outcome of the CAL 27 donor. OSCC with upregulated truncated CD82 and S100A7 may represent a distinct subtype with a poor prognosis. Differing alternatives from wild-type CD82 may elucidate the contradictory functions and pave the way for CD82 as a prognostic biomarker and therapeutic target.

Background: Ferroptosis is an iron-dependent cell death mode and closely linked to various cancers, including skin cutaneous melanoma (SKCM). Although attempts have been made to construct ferroptosis-related gene (FRG) signatures for predicting the prognosis of SKCM, the prognostic impact of ferroptosis-related genetic mutations in SKCM remains lacking. This study aims to develop a prediction model to explain the relationship between ferroptosis-related genetic mutations and clinical outcomes of SKCM patients and to explore the potential value of ferroptosis in SKCM treatment.Methods: FRGs which significantly correlated with the prognosis of SKCM were firstly screened based on their single-nucleotide variant (SNV) status by univariate Cox regression analysis. Subsequently, the least absolute shrinkage and selection operator (LASSO) and Cox regressions were performed to construct a new ferroptosis-related genetic mutation risk (FerrGR) model for predicting the prognosis of SKCM. We then illustrate the survival and receiver operating characteristic (ROC) curves to evaluate the predictive power of the FerrGR model. Moreover, independent prognostic factors, genomic and clinical characteristics, immunotherapy, immune infiltration, and sensitive drugs were compared between high—and low—FerrGR groups.Results: The FerrGR model was developed with a good performance on survival and ROC analysis. It was a robust independent prognostic indicator and followed a nomogram constructed to predict prognostic outcomes for SKCM patients. Besides, FerrGR combined with tumor mutational burden (TMB) or MSI (microsatellite instability) was considered as a combined biomarker for immunotherapy response. The high FerrGR group patients were associated with an inhibitory immune microenvironment. Furthermore, potential drugs target to high FerrGR samples were predicted.Conclusion: The FerrGR model is valuable to predict prognosis and immunotherapy in SKCM patients. It offers a novel therapeutic option for SKCM.

Summary: The pilosebaceous unit (PSU) is composed of multiple compartments and the self-renewal of PSU depends on distinct hair follicle stem cell (HFSC) populations. However, the differential roles of the HFSCs in sebaceous gland (SG) renewal have not been completely understood. Here, we performed multiple lineage tracing analysis to unveil the contribution of different HFSC populations to PSU regeneration during the hair cycle and wound healing. Our results indicated that the upper bulge stem cells contributed extensively to the SG replenishment during hair cycling, while HFSCs in the lower bugle did not. During skin wound healing, all HFSC populations participated in the SG replenishment. Moreover, β-catenin activation promoted the contribution of HFSCs to SG replenishment, whereas β-catenin deletion substantially repressed the event. Thus, our findings indicated that HFSCs contributed to SG replenishment in a β-catenin-dependent manner.

Polarized light detection is consequential for optical communication and polarized light imaging. InSe is considered a promising candidate for narrow‐bandgap photodetector. However, monolayer γ‐InSe is an indirect bandgap semiconductor and is ignored for a long time for polarized light detection. In this work, by virtue of the indirect–direct conversation and the surface‐bound excitons, the intrinsic anisotropy of multilayer γ‐InSe is revealed by the photoluminescence (PL) measurement under polarized light. Due to the anisotropy of surface‐bound exaction and in‐plane exciton, there are significant differences in the photocurrent under irradiation of laser with different polarization angles. The γ‐InSe‐based photodetector exhibits considerable polarization‐dependent photocurrent with an outstanding anisotropic ratio of 2.7. Moreover, the multilayer γ‐InSe photodetector shows high responsivity of 7.47 A W−1 and specific detectivity of 4.56 × 1013 Jones under 785 nm laser. Based on the InSe polarization photodetector, a polarization division multiplexing that can simultaneously process four information tracks and enhance the communication speed by 24 is explored. The multilayer InSe polarization photodetector proposed in this work broadens a new path for polarized light detection, and brings a potential solution to the field of optical communications.

Reinforced concrete has been widely used. However, it is difficult to accurately simulate the process of concrete damage and destruction caused by rebar corrosion. Therefore, the objective of this work is to solve this difficult problem using a phase field method and analyze the failure process of reinforced concrete. The main importance of this work is to improve the calculation method for the problem, simulate the damage and destruction of concrete cover, and visualize the crack propagation process. Based on the strain softening characteristics of concrete the damage of concrete cover caused by uniform and non-uniform corrosion of rebars is simulated respectively. The simulation results are consistent with the actual observation. The applicability of the phase field method for complex crack propagation in reinforced concrete is verified, which provides a reference for the engineering design and durability research of structures. Analysis of simulation results found that the crack propagation speed is fast for uniform corrosion. Increasing the thickness of concrete cover is benefit to improve the corrosion resistance of structure. However, the crack propagation speed is slow for non-uniform corrosion. The thickness of the cover has no obvious effect on the corrosion damage resistance of structure. For the non-uniform corrosion of multiple rebars, depending on the thickness of concrete cover and the spacing between rebars, the concrete cover presents three typical crack propagation morphologies: wedge-shaped cracks, layered cracks and small local cracks.

Sample mix-up is a potential problem in large-scale omic studies due to the complexity of sample processing. Here, the authors present a pipeline for sample matching in proteogenomics to verify sample identity and ensure data integrity.

As an essential part of hydrological cycle, groundwater circulation is a process including groundwater recharge, flow and discharge, which has been the primary research topic in hydrogeology.The spatial patterns of groundwater circulation are composed of different structure elements.There are two partitioning methods: the media structure determined from aquifer properties and the dynamic patterns determined according to the seepage field.A groundwater flow system (GFS) roles as a groundwater circulation cell within the concept of the dynamic patterns.In the last decade, significant advances have been achieved in the theory of GFSs, revealing groundwater circulation patterns in more comprehensive and deep ways.Studies on GFSs between parallel streams discovered that the top of water table is not the accurate position of groundwater divide.At the basin scale, the integrated impacts of the vale landform, precipitation infiltration rate, depth dependent permeability and basin thickness on the undulating shape of water table and groundwater circulation patterns were systematically investigated, with preliminary discovery on the evolution characteristics of dynamic patterns in periodicity and tendencies.Partitioning methods for three dimensional groundwater circulation cells were developed, according to fine-grained identification of paths or statistic analysis on residence times along a huge number of streamlines.For the hydrogeological effect, it has been found that the groundwater circulation patterns significantly influence the distribution of groundwater age.As an indication of hydraulic connection between recharge and discharge zones, groundwater circulation patterns play a key role in the geochemical processes at the basin scale and eco-hydrological processes at the catchment scale, which should be studied with more attentions on the dynamic and evolution behaviors of the three-dimensional groundwater circulation.

The theory of groundwater flow systems proposed by Tóth, which was based on the two-dimensional profile flow field, has become the theoretical basis for studying basin-scale groundwater circulation.The stagnation points on the two-dimensional profile can be used to accurately divide the spatial distribution of groundwater flow systems.However, the spatial distribution of groundwater flow systems and whether stagnation points exist in the 3D domain remain unknown.In this study, two typical three-dimensional basins, namely foreland-like basins with undulations only in the x direction and dune-type basins with undulations in both x and y directions, are used as typical examples.By using a combination of cosine functions to characterize the undulating water table, analytical solutions of head distribution in the two basins are derived.Moreover, by employing the TECPLOT software, the spatial distribution of the 3D groundwater flow systems is clearly shown.It is found out that stagnation points can develop in two basins.The stagnation points in the foreland-like basin constitute a horizontally extending stagnation line, which controls the spatial distribution of four flow systems in the basin, while the stagnation points in the dune-type basin form an arc-shaped stagnation line, which controls the spatial distribution of six flow systems in the basin.By studying the distribution of stagnation line in 3D basins and successfully dividing flow systems by using the stagnation line, this study leads to a deepened understanding of groundwater circulation in 3D basins.

The Kongqi River Irrigation District (KRID) in Xinjiang, China, has a serious problem of groundwater overexploitation.A scientific understanding of the development conditions and evolution characteristics of regional groundwater flow systems is the basis for optimizing the utilization of groundwater resources.The variation characteristics of groundwater flow systems in KRID, from 1970 to 2020, were simulated and identified via numerical modeling and streamlines tracing of the three-dimensional steady-state groundwater flow in the Quaternary aquifers.As indicated, a complex patterns of groundwater flow systems can be developed around the Kongqi River, with streamlines linking different recharge and discharge zones, varying with the pumping intensity of groundwater in KRID.In the 1970s when the condition was close to a natural state, groundwater flow systems with north-to-south flow dominated the irrigation district, and the spatial pattern depended on hydrogeological parameters and recharge-discharge factors.There were possibly 1-4 flow systems discharge to the Kongqi River in the natural condition.Currently, groundwater is strongly exploited in the irrigation district, and groundwater flow systems are attracted by the groundwater withdrawal funnel with recharge from surrounding areas, cutting off the groundwater flow system with recharge from the leaking upper reaches of the Kongqi River and discharge into the middle-lower reaches.In the past 50 years, the projected area for groundwater flow systems of the phreatic evaporation discharge has decreased by 29%, while the projected area for groundwater flow systems of pumping discharge has increased from zero to 40% of the total model area.Phreatic evaporation plays an important role in supporting natural ecosystems.Therefore, groundwater exploitation should be controlled in the irrigation district, to maintain the development condition for groundwater flow systems of phreatic evaporation discharge.

The theory of regional groundwater flow proposed by Tóth provides a quantitative analysis approach for the study of basin-scale groundwater circulation. This paper summarizes the development of the theory of regional groundwater flow from four aspects, compares the description of the theory of regional groundwater flow in foreign hydrogeology textbooks, and systematically summarizes the evolution of descriptions in the theory of regional groundwater flow in the four editions of the textbook "Fundamentals of hydrogeology" in Chinese published from 1986 to 2018. It is concluded that the textbook "Fundamentals of hydrogeology" plays an important role in promoting the study of regional groundwater flow in China. This paper also puts forward some scientific problems to be solved in the theory of regional groundwater flow and some suggestions to guide more young students to conduct research in this field.

Abstract Background Natural variation in protein expression is common in all organisms and contributes to phenotypic differences among individuals. While variation in gene expression at the transcript level has been extensively investigated, the genetic mechanisms underlying variation in protein expression have lagged considerably behind. Here we investigate genetic architecture of protein expression by profiling a deep mouse brain proteome of two inbred strains, C57BL/6 J (B6) and DBA/2 J (D2), and their reciprocal F1 hybrids using two-dimensional liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) technology. Results By comparing protein expression levels in the four mouse strains, we observed 329 statistically significant differentially expressed proteins between the two parental strains and characterized the genetic basis of protein expression. We further applied a proteogenomic approach to detect variant peptides and define protein allele-specific expression (pASE), identifying 33 variant peptides with cis-effects and 17 variant peptides showing trans-effects. Comparison of regulation at transcript and protein levels show a significant divergence. Conclusions The results provide a comprehensive analysis of genetic architecture of protein expression and the contribution of cis- and trans-acting regulatory differences to protein expression.

Abstract Mass spectrometry (MS)-based proteomics is a powerful tool to explore pathogenic changes of a disease in an unbiased manner and has been used extensively in Alzheimer disease (AD) research. Here, by performing a meta-analysis of high-quality proteomic studies, we address which pathological changes are observed consistently and therefore most likely are of great importance for AD pathogenesis. We retrieved datasets, comprising a total of 21,588 distinct proteins identified across 857 postmortem human samples, from ten studies using labeled or label-free MS approaches. Our meta-analysis findings showed significant alterations of 757 and 1,195 proteins in AD in the labeled and label-free datasets, respectively. Only 33 proteins, some of which were associated with synaptic signaling, had the same directional change across the individual studies. However, despite alterations in individual proteins being different between the labeled and the label-free datasets, several pathways related to synaptic signaling, oxidative phosphorylation, immune response and extracellular matrix were commonly dysregulated in AD. These pathways represent robust changes in the human AD brain and warrant further investigation.

Photocatalytic CO2 reduction to valuable hydrocarbon solar fuel is of great significance but still challenging. Strong CO2 enrichment ability and easily adjustable structures make metal-organic frameworks (MOFs) potential photocatalysts for CO2 conversion. Even though pure MOFs have the potential for photoreduction of CO2, the efficiency is still quite low due to rapid photogenerated electron–hole recombination and other drawbacks. In this work, graphene quantum dots (GQDs) were in situ encapsulated into highly stable MOFs via a solvothermal method for this challenging task. The GQDs@PCN-222 with encapsulated GQDs showed similar Powder X-ray Diffraction (PXRD) patterns to PCN-222, indicating the retained structure. The porous structure was also retained with a Brunauer–Emmett–Teller (BET) surface area of 2066 m2/g. After incorporation of GQDs, the shape of GQDs@PCN-222 particles remained, as revealed by the scanning electron microscope (SEM). As most of the GQDs were covered by thick PCN-222, it was hard to observe those GQDs using a transmission electron microscope (TEM) and a high-resolution transmission electron microscope (HRTEM) directly, the treatment of digested GQDs@PCN-222 particles by immersion in a 1 mM aqueous KOH solution can make the incorporated GQDs visible in TEM and HRTEM. The linker, deep purple porphyrins, make MOFs a highly visible light harvester up to 800 nm. The introduction of GQDs inside PCN-222 can effectively promote the spatial separation of the photogenerated electron–hole pairs during the photocatalytic process, which was proved by the transient photocurrent plot and photoluminescence emission spectra. Compared with pure PCN-222, the obtained GQDs@PCN-222 displayed dramatically enhanced CO production derived from CO2 photoreduction with 147.8 μmol/g/h in a 10 h period under visible light irradiation with triethanolamine (TEOA) as a sacrificial agent. This study demonstrated that the combination of GQDs and high light absorption MOFs provides a new platform for photocatalytic CO2 reduction.

In this study, a numerical model of two-phase flow boiling in a rod bundle channel was developed to investigate the influence of spacer grid's arrangement on thermal-hydraulic characteristics and critical heat flux (CHF). It was verified well by comparing with the experimental data obtained from 2006 look-up table, and the relative errors were within ±20% in most conditions. On this basis, taking a complex 5 × 5 rod bundle channel as an example, four different geometric models including bare rod bundle, rod bundles with upstream, downstream and two-Span spacer grid were established, respectively. It was found that upstream spacer grid has little influence on CHF, while CHF could be significantly improved by downstream spacer grid. Convective heat transfer coefficient of liquid phase can be increased a lot at the region of spacer grid, but enhancement effect of heat transfer only keeps a limited distance as the decreases of mixing effect of mixing vane. According to the distribution of secondary flow, the intensity of secondary flow caused by upstream spacer grid is weakened at the region of downstream spacer grid. Moreover, spacer grid would result in an increase of pressure drop, causing a certain pressure on the pump load.

Abstract Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer’s disease (AD). Here we review the advances and limitations in historic and recent AD proteomic research. Complementary to genetic mapping, proteomic studies not only validate canonical amyloid and tau pathways, but also uncover novel components in broad protein networks, such as RNA splicing, development, immunity, membrane transport, lipid metabolism, synaptic function, and mitochondrial activity. Meta-analysis of seven deep datasets reveals 2,698 differentially expressed (DE) proteins in the landscape of AD brain proteome (n = 12,017 proteins/genes), covering 35 reported AD genes and risk loci. The DE proteins contain cellular markers enriched in neurons, microglia, astrocytes, oligodendrocytes, and epithelial cells, supporting the involvement of diverse cell types in AD pathology. We discuss the hypothesized protective or detrimental roles of selected DE proteins, emphasizing top proteins in “amyloidome” (all biomolecules in amyloid plaques) and disease progression. Comprehensive PTM analysis represents another layer of molecular events in AD. In particular, tau PTMs are correlated with disease stages and indicate the heterogeneity of individual AD patients. Moreover, the unprecedented proteomic coverage of biofluids, such as cerebrospinal fluid and serum, procures novel putative AD biomarkers through meta-analysis. Thus, proteomics-driven systems biology presents a new frontier to link genotype, proteotype, and phenotype, accelerating the development of improved AD models and treatment strategies.

The phase-field method was used to simulate the propagation of concrete cracks and failure caused by corrosion and expansion of steel bars, which provides ideas for accurate simulation of the corrosion failure process of reinforced concrete (RC) and evaluation of structural durability. In this study, the entire process of corrosion and expansion of steel bars, resulting in cracks and finally falling off of the concrete protective layer, was successfully simulated. The simulation results were in good agreement with the actual observations. By setting different thicknesses of the protective layer, it was found that the thickness of the concrete protective layer had no obvious effect on limiting concrete cracks caused by the corrosion of steel bars. However, increasing the thickness of the protective layer can delay the speed of crack propagation. Simultaneously, considering the corrosion and expansion of multiple steel bars, according to the thickness of the protective layer and the spacing between the reinforcing bars, two forms of wedge-shaped cracking and laminar spalling of the protective layer are simulated. The simulation result is consistent with the actual observation phenomenon. This fully illustrates the possibility of using the phase-field method to simulate the corrosion fracture of RC and provides a reference for the engineering design and durability research of concrete structures.

Cr(VI) is one of the most toxic heavy metals, posing multiple threats to humans and ecosystems. Photoreduction of toxic Cr(VI) to para-toxic Cr(III) is one of the most effective ways to remove heavy metal chromium but is still challenging. Herein, Ti3C2/UiO-66-NH2 composites with different ratio of Ti3C2 were synthesized via an in situ solvothermal process and used for the enhanced photocatalytic removal of Cr(VI) for the first time. The UiO-66-NH2 nanoparticles were dispersed on the surface and slits of accordion-like Ti3C2 homogeneously. A strong interfacial interaction between Ti3C2 and UiO-66-NH2 was formed, which was indicated by the XPS. The Fermi level of the MXene cocatalyst is lower than UiO-66-NH2; thus, Ti3C2 can serve as the electron sink and accumulate photogenerated electrons from UiO-66-NH2 on its surface. A depletion layer was also formed due to the different Fermi levels of UiO-66-NH2 and Ti3C2, which prevents electrons from flowing back to UiO-66-NH. The strong interfacial interaction and formed depletion layer are beneficial for the following charge transfer from UiO-66-NH2 to Ti3C2 after light irradiation and for suppressing the photogenerated charge recombination. With suitable band positions and enhanced charge separation ability, Ti3C2/UiO-66-NH2 composites exhibited better photoreduction efficiency of Cr2O72− than pure Ti3C2 and UiO-66-NH2, with optimized samples reaching 100% in 40 min. The photoreduction kinetics of Cr2O72− by 2-T/U was also studied, with a photoreduction rate of 0.0871 min−1, which is about 2.6 times higher than that of the pure UiO-66-NH. This research provides a new type of efficient and environmentally friendly photocatalysts for the photoreduction of Cr2O72−.

Rationale: β-catenin signaling controls multiple fibroblast subsets, with its overactivity promoting the differentiation of hair follicle dermal stem cells (hfDSCs) and the hyperactivation of interfollicular fibroblasts. Understanding the concept of hfDSC activation and modulation offers hope towards the therapeutic armamentarium in dermatology and related comorbidities, as well as their potential applications in gerontology (the study of physiological aging). Having a comprehensive understanding in this stochastic process could also further yield important, novel insights into the molecular basis of skin aging to improve lifespan and preventing aging-related diseases.Methods: A new CD34CrePGR mouse line was generated. Through fate-tracing models and a series of β-catenin genetic experiments, our study depicts how the wound environment increases phosphorylated β-catenin in hfDSCs and facilitates their differentiation into dermal papilla (DP) and dermal sheath (DS). In mice carrying hfDSC-specific activated allele of β-catenin, hfDSCs accelerated their differentiation into DP cells.Results: Notably, with β-catenin stabilization in CD34-expressing cells and potential activation of canonical Wnt signaling, the mutant mice showed a brief increase of hair density in the short term, but over time leads to a senescence phenotype developing premature canities and thinning [hair follicle (HF) miniaturization].Conclusion: β-catenin signaling drove HF senescence by accelerating differentiation of CD34+ hfDSCs, resulting in phenotypes attributable to the differentiation of the hfDSCs into DP cells and the loss of their stem cell potential. Therefore, our study reveals that the regulation of β-catenin signaling in hfDSCs may potentially become an important subject for future exploration in development of clinically effective therapies for hair loss treatment and an excellent model for revealing new therapeutic approaches to reverse aging or retarding the development of alopecia.

Person transfer is a major problem for nursing in home and clinical, and this problem is becoming more prominent with the development of aging society and the change of population structure. In this article, a novel person transfer assist system named E-Pat (Easy-Patient Transfer), which can meet the transfer needs of the patient between beds, has been designed and analyzed. The importance and originality of this study are that it explores a theoretical design method for device to enhance patient comfortably when transferred, and put it into practice. The main tasks completed in this article include: (1) a prototype of the device is designed based on the principle of relative static contact point theory. In addition, the corresponding relationship between the human body pressure and the insertion angle is proposed, which provides a theoretical basis for the optimization of the mechanism; (2) based on STM32 (STMicroelectronics 32-bits Microcontroller) chip, the hardware circuit part of the device is designed. According to the transfer environment requirements of the device, the synchronization control algorithm of the device is designed and the experiment is carried out; (3) the performance evaluation of the device is carried out by means of Analytic Hierarchy Process (AHP), through the research of a group of 30 volunteers, the performance of the system has been evaluated accurately, which provides a reference for the industrialization of the prototype. The whole research of this article proves that this kind of person transfer assist system has good performance, it can also reduce the burden of caregivers.

Abstract Due to the strong liquid intermolecular force, feasible sensing‐detection methods in liquid environments are absent. Inspired by fish swim bladder, herein, a hollow‐structured microfiber is designed to realize high‐performance sensing in liquid environments. It composes of 2D polypyrrole (2DPPy) and reduced graphene oxide (rGO), and its wall has a porous skeleton of 2DPPy/rGO/2DPPy (2DPrG2DP). The internal cavities of porous skeleton will be filled by the liquid, while leaving a bubble inside the hollow micropipe due to the liquid surface tension, thus forming a solid/liquid/gas triple‐phase interface. This hollow microfiber transforms the unmanageable liquid‐phase sensing into gas‐phase sensing. During this process, the good mechanical strength of 2DPPy enables the high sensing operability, and the reversible gas extrusion‐withdraw process enables the high sensitivity. The hollow 2DPrG2DP microfiber‐based sensor can be potentially used to machine trouble shooting, water level monitoring, ocean current monitoring, tsunami warning, body fluid and blood monitoring, and oil transportation monitoring.

Deep reinforcement learning (DRL) provides a new solution for rehabilitation robot trajectory planning in the unstructured working environment, which can bring great convenience to patients. Previous researches mainly focused on optimization strategies but ignored the construction of reward functions, which leads to low efficiency. Different from traditional sparse reward function, this paper proposes two dense reward functions. First, azimuth reward function mainly provides a global guidance and reasonable constraints in the exploration. To further improve the efficiency, a process-oriented aspiration reward function is proposed, it is capable of accelerating the exploration process and avoid locally optimal solution. Experiments show that the proposed reward functions are able to accelerate the convergence rate by 38.4% on average with the mainstream DRL methods. The mean of convergence also increases by 9.5%, and the percentage of standard deviation decreases by 21.2%–23.3%. Results show that the proposed reward functions can significantly improve learning efficiency of DRL methods, and then provide practical possibility for automatic trajectory planning of rehabilitation robot.

Abstract Background Based on amyloid cascade and tau hypotheses, protein biomarkers of different Aβ and tau species in cerebrospinal fluid (CSF) and blood/plasma/serum have been examined to correlate with brain pathology. Recently, unbiased proteomic profiling of these human samples has been initiated to identify a large number of novel AD biomarker candidates, but it is challenging to define reliable candidates for subsequent large-scale validation. Methods We present a comprehensive strategy to identify biomarker candidates of high confidence by integrating multiple proteomes in AD, including cortex, CSF and serum. The proteomes were analyzed by the multiplexed tandem-mass-tag (TMT) method, extensive liquid chromatography (LC) fractionation and high-resolution tandem mass spectrometry (MS/MS) for ultra-deep coverage. A systems biology approach was used to prioritize the most promising AD signature proteins from all proteomic datasets. Finally, candidate biomarkers identified by the MS discovery were validated by the enzyme-linked immunosorbent (ELISA) and TOMAHAQ targeted MS assays. Results We quantified 13,833, 5941, and 4826 proteins from human cortex, CSF and serum, respectively. Compared to other studies, we analyzed a total of 10 proteomic datasets, covering 17,541 proteins (13,216 genes) in 365 AD, mild cognitive impairment (MCI) and control cases. Our ultra-deep CSF profiling of 20 cases uncovered the majority of previously reported AD biomarker candidates, most of which, however, displayed no statistical significance except SMOC1 and TGFB2. Interestingly, the AD CSF showed evident decrease of a large number of mitochondria proteins that were only detectable in our ultra-deep analysis. Further integration of 4 cortex and 4 CSF cohort proteomes highlighted 6 CSF biomarkers (SMOC1, C1QTNF5, OLFML3, SLIT2, SPON1, and GPNMB) that were consistently identified in at least 2 independent datasets. We also profiled CSF in the 5xFAD mouse model to validate amyloidosis-induced changes, and found consistent mitochondrial decreases (SOD2, PRDX3, ALDH6A1, ETFB, HADHA, and CYB5R3) in both human and mouse samples. In addition, comparison of cortex and serum led to an AD-correlated protein panel of CTHRC1, GFAP and OLFM3. In summary, 37 proteins emerged as potential AD signatures across cortex, CSF and serum, and strikingly, 59% of these were mitochondria proteins, emphasizing mitochondrial dysfunction in AD. Selected biomarker candidates were further validated by ELISA and TOMAHAQ assays. Finally, we prioritized the most promising AD signature proteins including SMOC1, TAU, GFAP, SUCLG2, PRDX3, and NTN1 by integrating all proteomic datasets. Conclusions Our results demonstrate that novel AD biomarker candidates are identified and confirmed by proteomic studies of brain tissue and biofluids, providing a rich resource for large-scale biomarker validation for the AD community.

Abstract Background Cultured epidermal stem cells (Epi-SCs) and skin-derived precursors (SKPs) were capable of reconstituting functional hair follicles after implantation, while the signaling pathways that regulate neogenic hair follicle formation are poorly investigated. In this study, we aimed to understand the interactions between Epi-SCs and SKPs during skin organoid formation and to uncover key signal pathways crucial for de novo hair follicle regeneration. Methods To track their fate after transplantation, Epi-SCs derived from neonatal C57BL/6 mice were labeled with tdTomato, and SKPs were isolated from neonatal C57BL/6/GFP mice. A mixture of Epi-SCs-tdTomato and SKPs-EGFP in Matrigel was observed under two-photon microscope in culture and after implantation into excisional wounds in nude mice, to observe dynamic migrations of the cells during hair follicle morphogenesis. Signaling communications between the two cell populations were examined by RNA-Seq analysis. Potential signaling pathways revealed by the analysis were validated by targeting the pathways using specific inhibitors to observe a functional loss in de novo hair follicle formation. Results Two-photon microscopy analysis indicated that when Epi-SCs and SKPs were mixed in Matrigel and cultured, they underwent dynamic migrations resulting in the formation of a bilayer skin-like structure (skin organoid), where Epi-SCs positioned themselves in the outer layer; when the mixture of Epi-SCs and SKPs was grafted into excisional wounds in nude mice, a bilayer structure resembling the epidermis and the dermis formed at the 5th day, and de novo hair follicles generated subsequently. RNA-Seq analysis of the two cell types after incubation in mixture revealed dramatic alterations in gene transcriptome, where PI3K-Akt signaling pathway in Epi-SCs was significantly upregulated; meanwhile, elevated expressions of several growth factors and cytokine potentially activating PI3K were found in SKPs, suggesting active reciprocal communications between them. In addition, inhibition of PI3K or Akt by specific inhibitors markedly suppressed the hair follicle regeneration mediated by Epi-SCs and SKPs. Conclusions Our data indicate that the PI3K-Akt signaling pathway plays a crucial role in de novo hair follicle regeneration, and the finding may suggest potential therapeutic applications in enhancing hair regeneration.

Seawater quality prediction has a tremendous potential of enabling future smart ocean. However, this time-sensitive application puts forward a strict delay requirement, thus easily leading to overwhelmed networks. Edge computing is emerging as an effective means of solving network overload, due to its edge-based distributed processing. Therefore, we develop a hybrid multivariate prediction model for seawater quality assessment in an edge computing environment, considering the combination of principal component analysis (PCA) and relevance vector machine (RVM). The PCA method is employed for dimension reduction of ten seawater quality factors in advance. Six principal components are extracted from multiple features, used as input variables of the subsequent predictor. Finally, a RVM is developed to predict the future trends of dissolved oxygen and pH, measuring seawater quality. Experimental results on the real-world ocean sensor data show that our PCA-RVM based multivariate prediction model outperforms single RVM, SVM and its extended version in prediction accuracy and efficiency, meanwhile statistical testings confirm this finding.

Given that humans and animals can learn new behaviors in a short time by observing others, the question we need to consider is how to make robots behave like humans or animals, that is, through effective demonstration, robots can quickly understand and learn a new ability. One possible solution is imitation based meta-learning, but most of the related approaches are limited in a particular network structure or a specific task. Particularly, meta-learning methods based on gradient-update are prone to overfit. In this article, we propose a generic meta-learning algorithm that divides the learning process into two independent stages (skill cloning and skill transfer) with a noise mechanism which is compatible with any model. The skill cloning stage enables a good understanding of the demonstration, which helps the skill transfer stage when the robot applies the learned experience into new tasks. The experimental results show that our algorithm can alleviate the phenomenon of overfitting by introducing a noise mechanism. Our method not only performs well on the regression task but is significantly better than the existing state-of-the-art one-shot imitation learning methods in the same simulation environments (i.e., simulated pushing and simulated reaching).

In recent years, the rapid development of electric vehicles, smart grids, and portable electronic devices have given a boost to energy storage devices represented by rechargeable batteries. Seeking for reliable security, cost‐effectiveness, and especially high energy density of rechargeable batteries is the crucial demand. The key to improve energy density of rechargeable batteries is adopting high theoretical capacity electrodes or reducing the content of nonredox components. Unfortunately, some problems such as poor cycle stability and low rate performance caused by poor conductivity and unstable structure limit the application of high‐capacity electrodes. Conducting polymers (CPs) are widely used to modify electrode materials to promote the carrier transport and suppress the volume expansion during cycles due to their good conductivity, electroactivity, and machinability. In this Review, the conductive mechanisms, synthesis methods, and the applications in modifying electrodes with CPs are discussed. Also, the recent progresses about CPs‐modified electrodes including coating, intercalation, and carbonization in rechargeable batteries are summarized. Finally, the challenges and the further developments for modifying electrodes with CPs, which aims to provide the assistance for developing high‐performance CPs composite electrodes, are proposed.

Abstract A disordered phase in Li‐deposit nanostructure is greatly attractive, but plagued by the uncontrollable and unstable growth, and the nanoscale characterization in the structure. Here, fully characterized in cryogenic transmission electron microscopy (cryo‐TEM), more robust amorphous‐Li (ALi) clusters are revealed and effectively regulated on heteroatom‐activating electronegative sites and an advanced solid electrolyte interphase (SEI) layer. Heteroatom‐activating electronegative sites capably enhance the electrostatic interaction of Li+ and heteroatom‐doping graphene‐like film (HDGs), meaning lower Li diffusion barrier and larger binding energy that is confirmed by small nucleation overpotentials of 13.9 and 10 mV at 0.1 mA cm−2 in the fluoroethylene carbonate‐adding ester‐based (FEC‐ester) and LiNO3‐adding ether‐based (LiNO3‐ether) electrolytes. Orderly multilayer SEI structure comprised of inorganic‐rich components enables fast ion transports and durable capabilities to construct highly reversible and long‐term plating/stripping cycling. ALi cluster anodes exhibit non‐crystalline morphologies and perform ultrastable dendrite‐free cycling over 2800 times. Stable ALi clusters are also grown in LiFePO4 (LFP) (LFP‐ALi‐HDGs‐N||LiFePO4 [LFP]) full cells with advantageous capacities up to 165.5 and 164.3 mAh g−1 in these optimized electrolytes at 0.1 C; the remarkable capacity retentions maintain to 93% and 91% after 150 cycles at 0.2 C. Structure viability, electrochemical reversibility, and excellent performance in ALi clusters are effectively regulated.

Epidemiology occupies a very important position in preventive medicine. Its essence is to summarize the etiology and epidemic laws by studying the distribution and possible effects of diseases, so as to promote the formation of scientific epidemic prevention measures. The purpose of this article is to help relevant personnel complete the collection, induction, and analysis of epidemiological survey data by establishing a data collection system model to improve work efficiency. This article focuses on the new coronavirus pneumonia (COVID-19), investigates the development status of epidemiological survey data collection, and analyzes the problems in the current business process, and on this basis, develops a dedicated epidemiological survey System model for data collection. From the experimental data, the optimized correction evaluation index has been increased from 8.384 to 9.067. It can be seen that the combination of data mining algorithms and backpropagation algorithms can better improve the system's ability to process information. Professional information disclosure platforms can have a good positive impression on the prevention and treatment of epidemics. The Internet-based epidemiological survey customized system model established in this article is to integrate various epidemiological data so that people can correctly understand the spread of epidemics and promote the development of preventive medicine.

To provide stroke patients with good rehabilitation training, the rehabilitation robot should ensure that each joint of the limb of the patient does not exceed its joint range of motion. Based on the machine vision combined with an RGB-Depth (RGB-D) camera, a convenient and quick human-machine interaction method to measure the lower limb joint range of motion of the stroke patient is proposed. By analyzing the principle of the RGB-D camera, the transformation relationship between the camera coordinate system and the pixel coordinate system in the image is established. Through the markers on the human body and chair on the rehabilitation robot, an RGB-D camera is used to obtain their image data with relative position. The threshold segmentation method is used to process the image. Through the analysis of the image data with the least square method and the vector product method, the range of motion of the hip joint, knee joint in the sagittal plane, and hip joint in the coronal plane could be obtained. Finally, to verify the effectiveness of the proposed method for measuring the lower limb joint range of motion of human, the mechanical leg joint range of motion from a lower limb rehabilitation robot, which will be measured by the angular transducers and the RGB-D camera, was used as the control group and experiment group for comparison. The angle difference in the sagittal plane measured by the proposed detection method and angle sensor is relatively conservative, and the maximum measurement error is not more than 2.2 degrees. The angle difference in the coronal plane between the angle at the peak obtained by the designed detection system and the angle sensor is not more than 2.65 degrees. This paper provides an important and valuable reference for the future rehabilitation robot to set each joint range of motion limited in the safe workspace of the patient.