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Fine-scale population spatial distribution plays an important role in urban microcosmic research, influencing infrastructure placement, emergency evacuation management, business decisions, and urban planning. In the past, nighttime light (NTL) data were generally used to map the spatial distribution of the population at a large scale because of their low spatial resolution. The new generation of Luojia1-01 NTL data can be used for fine-scale social and economic analysis with its high spatial resolution and quantitative range. However, due to the geometry and background noise of the data themselves, the accuracy of the original NTL data is still low. Points-of-interest (POI) also can be used to map the population spatialization, but the indicative relationship between the POI and population is not clear, especially in rural and urban areas with different landscape structures. To solve the above-mentioned problems, this study proposes an improved nighttime light (INTL) index to better use the Luojia1-01 NTL data. Meanwhile, a zonal classification model based on INTL and impervious surface area is proposed to distinguish urban and rural areas. Compared with previous research and existing datasets, our result had the highest accuracy (R² = 0.86). This study explains that the INTL index is applicable to population spatialization research with the emergence of high-resolution and multispectral NTL satellite data. Moreover, the zonal classification model in this research can significantly improve the accuracy of population spatialization in rural areas. This study provides a possible way to use NTL and POI data in other social and economic spatialization research.

Abstract The range‐angle coupling characteristics of traditional frequency diverse array (FDA) will deteriorate target localization performance. To address this problem, several decoupling methods for FDA have been developed in the past decade, mainly including deterministic methods and global optimization methods. However, most of these methods are based on frequency offset design and do not fully utilize other design degrees of freedom, such as excitation and element spacing, which limits obtained pattern performance. In this letter, a low‐sidelobe FDA pattern synthesis method is proposed by jointly optimizing frequency offset, array spacing and excitation. The entire optimization process is treated as two sub‐optimization problems, that is, a non‐convex sub‐problem involves frequency offset and array spacing, and a convex sub‐problem involves excitation. By integrating the mayfly algorithm and convex programming techniques, this synthesis problem can be effectively solved. Compared with the current state‐of‐the‐art counterparts, the proposed method takes full advantage of the FDA's design freedom and generates a doted beampattern with lower sidelobes.

Pseudocapacitive materials with surface‐redox reactions are capable of realizing high capacities at ultrahigh rates; however, it remains a challenge in the synthesis of active components with high surface area to boost surface‐redox sodiation but restrain side reactions. Herein, a two‐step, topochemical synthesis of 2D mesoporous TiN (2D‐meso‐TiN) with high surface area and rich mesoporosities is presented. It is demonstrated that the sodium‐ion storage mechanism of TiN anode is based on the existence of surficial titanium oxides via redox reactions between Ti4+ and Ti3+. The interconnected, highly conductive 2D‐meso‐TiN with high surface area largely increases the pseudocapacitive capacities, leading to a high capacity of 160/93 mAh g−1 at 0.1/10 A g−1, which is much higher than 2D‐TiN (120/72 mAh g−1) and commercial TiN nanoparticles (57/30 mAh g−1). The surface‐redox (de)sodiation undergoes no destruction of crystalline TiN, which enables high initial coulombic efficiency and long‐term cycles. Furthermore, a novel hybrid sodium‐ion capacitor consisting of 2D‐meso‐TiN anode and Na3V2(PO4)3 cathode is assembled without any presodiation treatments. The hybrid capacitor delivers both high energy density (94 Wh kg−1 at 64 W kg−1) and high power density (38 Wh kg−1 at 4.4 kW kg−1), as well as long cycling stability.

The study used headspace solid-phase microextraction coupled with gas chromatography-time-of-flight mass spectrometry (HS–SPME–GC–TOF–MS) to analyze volatile compounds in leaves and fruits of Amomum tsaoko, Amomum paratsaoko, and Amomum koenigii. The composition and aroma of distinct metabolites were analyzed using multivariate statistical methods. A total of 564 volatile compounds were identified from three species of the genus Amomum, which were further divided into nine categories: terpenoids, carboxylic acids, alcohols, hydrocarbons, aldehydes, ketones, phenols, ethers, and other compounds. Terpenoids and alcohols were the most abundant. The content and types of compounds vary in A. tsaoko, A. paratsaoko, and A. koenigii, so mixing or substituting them is not advisable. We selected 45 metabolites based on the criteria of the variable importance in projection values (VIP > 1.5) and one-way ANOVA (p < 0.05). The top 19 metabolites with the most significant VIP values were chosen. Interestingly, (Z)-2-decenal was only found in Amomum koenigii, while nitroethane and nonanal were only present in cultivated A. tsaoko. Additionally, linalool, cineole, and (D)-limonene were the main components affecting the aroma of three species of the genus Amomum. The volatile components identified in this study provide a theoretical basis for analyzing the unique flavor of A. tsaoko, A. paratsaoko, and A. koenigii.

Evapotranspiration (ET) is the most significant constituent of the response to climate warming. It serves as a crucial link in the soil–vegetation–atmospheric continuum. Analyzing the driving forces and response of ET to regional-scale climate warming holds scientific significance in improving global water resource assessment methods and drought monitoring techniques. The innovation presented in this article is the calculation of ET by using GRACE/GRACE-FO satellite data through the water balance equation. The inter-annual and seasonal changes in ET in different regions of the Qilian Mountains were analyzed, along with quantifying the contribution of environmental meteorological factors to ET. The ETGRACE and ETMonitor products have good consistency, with a monthly correlation coefficient of 0.92, an NSE coefficient of 0.80, and a root mean square error of 10.38 mm. The results indicate that the increasing trend of ET in the Qilian Mountains region exhibits a “medium–high–low” distribution pattern. The rate of increase in ET is 5.2 mm/year in the central segment. In spring and summer, the overall trend of ET is an increasing one. However, the central and western segments exhibit a slight decreasing trend of ET in autumn. During winter, the southern part of the Qilian Mountains experiences a notable reduction in ET. The correlation between the changes in ET and soil moisture exhibited a strong association, with soil moisture change contributing significantly to ET: 57.8% for the eastern section, 52.8% for the middle section, and 46.9% for the western section. The thermal effect primarily controls ET variations within eastern sections, where temperature change accounts for approximately 6.7% of the total variation in ET levels. Conversely, the moisture factor dominates western sections, where precipitation change accounts for about 6.5% of the total variation in ET levels. Due to the distinct gradient characteristics of environmental meteorological factors in the central segment, the fluctuation of these factors collaboratively drives ET changes. This article provides a new approach for obtaining continuous and reliable actual evapotranspiration in high-altitude areas.

Glycans are among the most important cell molecular components. However, given their structural diversity, their functions have not been fully explored. Glycosylation is a vital post-translational modification for various proteins. Many bacteria and viruses rely on N-linked and O-linked glycosylation to perform critical biological functions. The diverse functions of glycosylation on viral proteins during viral infections, including Dengue, Zika, influenza, and human immunodeficiency viruses as well as coronaviruses have been reported. N-linked glycosylation is the most common form of protein modification, and it modulates folding, transportation and receptor binding. Compared to N-linked glycosylation, the functions of O-linked viral protein glycosylation have not been comprehensively evaluated. In this review, we summarize findings on viral protein glycosylation, with particular attention to studies on N-linked glycosylation in viral life cycles. This review informs the development of virus-specific vaccines or inhibitors.

Abstract By controlling the null distribution in the range‐angle dimension, the frequency diverse array (FDA) can handle range‐dependent interference, which is usually difficult to solve for the traditional phased array. However, the current investigations focus more on the design of weights for null control, ignoring the unique design dimension of FDA, that is, the frequency offsets. Therefore, the array potential cannot be fully exploited to maximise the range‐dependent interference suppression capability. In this paper, a novel FDA synthesis method with large null depth is proposed. By incorporating the mayfly algorithm and convex programing, frequency offsets and transmit weights are jointly optimised to generate maximum null depths in a given region while maintaining the specified array response of the desired target. Other null control methods for FDA are listed as comparison, including weights‐only optimisation method, frequency offsets‐only optimisation and frequency offsets and weights sequentially optimisation method. Numerical examples demonstrate the superiority of the proposed algorithm.

Abstract Background Brazil, China, Kazakhstan, and Russia are the main asbestos-producing countries, and all forms of asbestos are carcinogenic to humans. The objective of this study was to estimate the disease burden attributable to asbestos between 1990 and 2019 in major producing countries, including Brazil, China, Kazakhstan, and Russia. Methods Age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life year (DALY) rates (ASDR) of disease burden attributable to asbestos by country, age, and sex were extracted from the Global Burden of Disease 2019. Percentage change and estimated annual percentage change (EAPC) were used to assess the trends of ASDR and ASMR of disease burden attributable to asbestos between 1990 and 2019. Results Asbestos-related diseases were highly heterogeneous across Global, Brazil, China, Kazakhstan, and Russia. There was a downward trend in ASMR and ASDR of diseases burden related to asbestos globally. The age-specific mortality rate of disease attributable to asbestos increased in men and women, although it decreased in women aged 85–89, the highest age-specific mortality rate were observed in age 95 + group in men [162.14 (95% UI: 103.76–215.45)] and women [30.58 (95% UI: 14.83–44.33)] per 100 000 population, respectively. Tracheal, bronchus, and lung (TBL) cancer was the leading cause of death and DALYS attributable to asbestos between 1990 and 2019 globally and in Brazil, China, Kazakhstan, and Russia. China had the highest percentage change (73.31%) and EAPC [3.41 (95% CI: 2.75–4.08)] in ASMR related to exposure to asbestos in men, with the highest percentage change (73.31%) and EAPC [3.41 (95% CI: 2.75–4.08)] in ASDR in men. Conclusions The ASMR and ASDR of disease burden attributable to asbestos decreased between 1990 and 2019 globally. TBL cancer was the leading cause of death and DALYs attributable to asbestos between 1990 and 2019. There has been an increasing trend in mortality and DALYs globally, especially in older men. The burden of disease attributable to asbestos is increasing in China, especially in men.

Abstract Industry and research communities have widely studied Blockchain technology, and the consortium blockchain is currently the most used category with a wide range of applications. However, issues, such as the performance of consensus mechanisms, have become essential constraints on promoting and applying the consortium blockchain. To improve the performance of the consortium blockchain consensus, we use the practical Byzantine fault tolerance (PBFT) consensus widely used in consortium blockchains to reduce the number of consensus nodes to optimize performance. Using the PBFT consensus, we screen high-performance nodes and obtain a reliable and limited number of consensus nodes. We propose a genetic algorithm-based blockchain consensus algorithm improvement scheme, design the fitness function of blockchain nodes and the genetic algorithm to iterate out consensus node groups with excellent indicators continuously, and finally iterate the nodes participating in the consensus. This algorithm can increase the speed and efficiency of the consensus, block generation, and computation. The algorithm in this article is tested on the FISCO BCOS (i.e., a consortium blockchain platform built by the FISCO open-source working group), and controlled experiments and the experimental results illustrate the safety and practicability of the method.

Abstract C − Si Bond cleavage is one of the key elemental steps for a wide variety of silicon-based transformations. However, the cleavage of unstrained Si−C(sp3) bonds catalyzed by transition metal are still in their infancy. They generally involve the insertion of a M − C(sp2) species into the C − Si bond and consequent intramolecular C(sp2)‒Si coupling to exclusively produce siloles. Here we report the Pd-catalyzed sila-spirocyclization, in which the Si−C(sp3) bond is activated by the insertion of a M − C(sp3) species and followed by the formation of a new C(sp3)‒Si bond, allowing the construction of diverse spirosilacycles. This reactivity mode, which is strongly supported by DFT calculations may open an avenue for the Si−C(sp3) bond cleavage and silacycle synthesis.

It is challenging to obtain Ti alloys with ultrafine microstructure owing to the low thermal stability of crystallographic boundaries. Here the authors demonstrate a chemical boundary-based strategy to produce a hierarchical Ti alloy with nano-martensites that has excellent strength and ductility.

Summary: Prolonged withdrawal from opioids leads to negative emotions. Kappa opioid receptor (KOR) plays an important role in opioid addiction and affective disorders. However, the underlying mechanism of KOR in withdrawal-related depression is still lacking. We found that escitalopram treatment had a limited effect in improving depression symptoms in heroin-dependent patients. In mice, we demonstrated prolonged (4 weeks) but not acute (24 h) withdrawal from morphine induced depressive-like behaviors. The number of c-Fos positive cells and the expression of KOR in the nucleus accumbens (NAc), were significantly increased in the prolonged morphine withdrawal mice. Conditional KOR knockdown in NAc significantly improved depressive-like behaviors. Repeated but not acute treatment with the KOR antagonist norBNI improved depressive-like behaviors and reversed PSD95, synaptophysin, p-ERK, p-CREB, and BDNF in NAc. This study demonstrated the important role of striatal KOR in morphine withdrawal-related depressive-like behaviors and offered therapeutic potential for the treatment of withdrawal-related depression.

One of the long-term concerns regarding titanium alloy wires involves microstructural inhomogeneity, mechanical instability and product unreliability in service. In this study, a strategy of micro-alloying was utilized to address the issue in Ti-6Cr-5Mo-5V-4Al (Ti6554) β-titanium alloy wires. The microstructures and mechanical properties of Ti6554 hot-rolled wires were optimized through boron (B) additions. The results manifest that B-addition promotes microstructural homogenization of wires, wherein the microstructure nearly completely consists of normal grain region (NGR) without abnormal grain region (AGR) like that in the B-free alloys. This microstructural homogenization relieves mechanical fluctuation amongst different samples and renders plastic flow highly repeatable upon stretching. Meanwhile, B-addition strengthens wires whilst maintains decent ductility and thereby achieves the better combination of strength and ductility in comparison with that in the B-free wires. The analyses indicate that the addition of B facilitates the universal occurrence of dynamic recrystallization (DRX) to form NGRs at the expense of AGRs, which is beneficial to microstructural homogenization of hot-rolled wires. A good plastic accommodation resulting from NGRs and strengthening caused by TiB laths endow Ti6554 wires superior strength-ductility synergy. These findings provide helpful guidance for microstructural and performance optimization of titanium alloy wires.

Abstract For dry adhesive–based operation, highly adaptable and stable manipulation is important but also challenging, especially for irregular objects with complex surface (such as abrupt profile and acute projection) under vibration‐inducing environments. Here, a multi‐scale adhesive structure, with mechanically isolated energy‐absorbing backing, based on the synergistic action of microscale contact end (seta), mesoscale supporting layer (lamella), and macroscopic backing (muscle tissues) of gecko's sole, is proposed. Top layer of mushroom‐like micro tips provides dry adhesion via mimicking gecko's seta, and bottom layer of physical cuts and porous feature achieves the interfacial mechanical decoupling and crack inhibition via mimicking the non‐continuous distributing of lamella and compliance of muscle. The proposed dry adhesive exhibits excellent adaptable adhesion to various objects with curved or irregular surfaces, even for that with abrupt contours, as well as an amazing stable anti‐vibration ability, opening a new avenue for the development of dry adhesive–based device or system.

Carbon (C) release from plant and microbial residues is a primary pathway of energy flow from photosynthetic and metabolic biomass to carbon dioxide (CO _2 ) in terrestrial ecosystems. Traditional view show that microbial residue C is more resistant to decompose than plant litter because their smaller particle sizes could be preferentially occluded in microaggregates with less microbial accessibility. However, we still lack a quantitative assessment (i.e. isotopic C labeling) to isolate the progressive release of C fractions from both plant and microbial residues. Here we used a global data set of 117 decomposition experiments that traced the ^13 C or ^14 C release of isotopically labeled plant and microbial residues to estimate the C release rates and turnover times by using a first-order exponential kinetics model. The average C release rates of crop, grass and tree litter were 7.78, 3.79 and 2.11 yr ^−1 , which were significantly lower than microbial residues (13.07 yr ^−1 ). Although C release rates of both plant and microbial residues were positively correlated with site temperature, the mean turnover time of microbial residues was 2–6 times lower than plant litter. We suggest that a constraint in microbial and plant residues leads to a predictable pattern of C release during terrestrial decomposition, which could be included in Earth system models.

Abstract Background Ticks are hematophagous parasites that transmit an extensive range of pathogens to their vertebrate hosts. Ticks can destroy invading microorganisms or alleviate infection via their rudimentary but orchestrated innate immune system. Antimicrobial peptides (AMPs) are important components of tick innate immunity. Among these humoral effector molecules, defensins are well-studied and widely identified in various species of Ixodidae (hard ticks) and Argasidae (soft ticks). This review was aimed at presenting the characterization of tick defensins from structure-based taxonomic status to antimicrobial function. Main text All published papers written in English from 2001 to May 2022 were searched through PubMed and Web of Science databases with the combination of relevant terms on tick defensins. Reports on identification and characterization of tick defensins were included. Of the 329 entries retrieved, 57 articles were finally eligible for our scoping review. Tick defensins mainly belong to the antibacterial ancient invertebrate-type defensins of the cis-defensins superfamily. They are generally small, cationic, and amphipathic, with six cysteine residues forming three intra-molecular disulfide bonds. Tick defensins primarily target membranes of a variety of pathogens, including Gram-positive and Gram-negative bacteria, fungi, viruses, and protozoa. Since tick defensins have a high degree of variability, we summarize their common biological properties and enumerate representative peptides. Along with the various and potent antimicrobial activities, the role of tick defensins in determining vector competence is discussed. Conclusions Due to their broad-spectrum antimicrobial activities, tick defensins are considered novel candidates or targets for controlling infectious diseases. Graphical Abstract

Low-temperature decomposition and insufficient plastic deformability are bottlenecks that limit the practical applications of nanograined Al alloys. Here the authors utilize a high density vacancies in combination with Sc microalloying to stabilize nanograined Al-Cu alloys.

Abstract Animal chimeras are widely used for biomedical discoveries, from developmental biology to cancer research. However, the accurate quantitation of mixed cell types in chimeric and mosaic tissues is complicated by sample preparation bias, transgenic silencing, phenotypic similarity, and low-throughput analytical pipelines. Here, we have developed and characterized a droplet digital PCR single-nucleotide discrimination assay to detect chimerism among common albino and non-albino mouse strains. In addition, we validated that this assay is compatible with crude lysate from all solid organs, drastically streamlining sample preparation. This chimerism detection assay has many additional advantages over existing methods including its robust nature, minimal technical bias, and ability to report the total number of cells in a prepared sample. Moreover, the concepts discussed here are readily adapted to other genomic loci to accurately measure mixed cell populations in any tissue.

Abstract This study is to investigate whether astaxanthin could alleviate the oxidative stress damages of follicles induced by BPA and improve the development of the cultured follicles and oocytes. Compared with BPA group, the survival rate, antrum formation rate, oocyte maturation rate and adherence area of the D8 and D10 follicles of the BPA+Asta group were significantly higher. The estrogen and progesterone in the culture medium of BPA+Asta group were significantly higher. PCNA in D8 and D10 granulosa cells and ERα in D10 granulosa cells of follicles in BPA+Asta group were significantly higher. The levels of malondialdehyde in the follicle culture medium, levels of ROS in the oocytes, the expression levels of caspase 3 and cathepsin B in the oocytes of the BPA+Asta group were significantly lower. However, the mitochondrial membrane potential, and the expression levels of antioxidant genes (CAT, SOD1 and SOD2) and anti-apoptotic gene Bcl-2 in the oocytes in the BPA+Asta group were significantly higher. Astaxanthin improves the development of follicles and oocytes through increasing the antioxidant capacity of follicles and oocytes, and relieving the BPA-induced oxidative stress during follicular development and oocyte maturation.

IntroductionPolygonatum kingianum is a traditional medicinal plant, and processing has significantly impacts its quality.MethodsTherefore, untargeted gas chromatography-mass spectrometry (GC-MS) and Fourier transform-near-infrared spectroscopy (FT-NIR) were used to analyze the 14 processing methods commonly used in the Chinese market.It is dedicated to analyzing the causes of major volatile metabolite changes and identifying signature volatile components for each processing method.ResultsThe untargeted GC-MS technique identified a total of 333 metabolites. The relative content accounted for sugars (43%), acids (20%), amino acids (18%), nucleotides (6%), and esters (3%). The multiple steaming and roasting samples contained more sugars, nucleotides, esters and flavonoids but fewer amino acids. The sugars are predominantly monosaccharides or small molecular sugars, mainly due to polysaccharides depolymerization. The heat treatment reduces the amino acid content significantly, and the multiple steaming and roasting methods are not conducive to accumulating amino acids. The multiple steaming and roasting samples showed significant differences, as seen from principal component analysis (PCA) and hierarchical cluster analysis (HCA) based on GC-MS and FT-NIR. The partial least squares discriminant analysis (PLS-DA) based on FT-NIR can achieve 96.43% identification rate for the processed samples.DiscussionThis study can provide some references and options for consumers, producers, and researchers.

Non-ribosomal peptide synthetase (NRPS) is a diverse family of biosynthetic enzymes for the assembly of bioactive peptides. Despite advances in microbial sequencing, the lack of a consistent standard for annotating NRPS domains and modules has made data-driven discoveries challenging. To address this, we introduced a standardized architecture for NRPS, by using known conserved motifs to partition typical domains. This motif-and-intermotif standardization allowed for systematic evaluations of sequence properties from a large number of NRPS pathways, resulting in the most comprehensive cross-kingdom C domain subtype classifications to date, as well as the discovery and experimental validation of novel conserved motifs with functional significance. Furthermore, our coevolution analysis revealed important barriers associated with re-engineering NRPSs and uncovered the entanglement between phylogeny and substrate specificity in NRPS sequences. Our findings provide a comprehensive and statistically insightful analysis of NRPS sequences, opening avenues for future data-driven discoveries.

Sporadic Alzheimer’s disease (sAD) is the most common neurodegenerative disease worldwide, which is characterized by the progressive cognitive dysfunction and behavioral impairment. Here, we generated a human induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) isolated from a 78-year-old male patient clinically diagnosed with sAD. The iPSC line expressed pluripotency markers, showed normal karyotype, and had the ability to differentiate into three germ layers in vitro. This iPSC line may provide a powerful tool for modeling AD in vitro and studying the pathogenesis of sAD.

Abstract Background and objectives Combined hepatocellular cholangiocarcinoma (cHCC) has a high incidence of early recurrence. The objective of this study is to construct a model predicting very early recurrence (VER) (i.e., recurrence within 6 months after surgery) of cHCC. Methods One hundred thirty-one consecutive patients from Eastern Hepatobiliary Surgery Hospital served as a development cohort to construct a nomogram predicting VER by using multi-variable logistic regression analysis. The model was internally and externally validated in a validation cohort of 90 patients from Mengchao Hepatobiliary Hospital using the C concordance statistic, calibration analysis, and decision curve analysis (DCA). Results The VER nomogram contains microvascular invasion (MiVI), macrovascular invasion (MaVI), and CA19-9 > 25 mAU/mL. The model shows good discrimination with C-indexes of 0.77 (95% CI: 0.69–0.85) and 0.76 (95% CI: 0.66–0.86) in the development cohort and validation cohort respectively. Decision curve analysis demonstrated that the model is clinically useful and the calibration of our model was favorable. Our model stratified patients into two different risk groups, which exhibited significantly different VER. Conclusions Our model demonstrated favorable performance in predicting VER in cHCC patients.

Two new sesquiterpenoids, 1–2, together with three known compounds, were isolated from Trichoderma hypoxylon. Among the known compounds, compound 4 was isolated as naturally occurring compound for the first time. The structures of these new compounds were characterized by HR-ESI-MS and spectroscopic methods including 1D and 2D NMR. The absolute configurations of 1–2 were assigned by electronic circular dichroism (ECD) calculations.

Abstract Inspired by butterfly wing architectures, a facile but efficient approach is developed to realize three sensing characteristics in a single pressure sensor by harnessing hierarchical wrinkling‐cracking architectures, including i) wrinkling‐dominant (WD) mode, ii) wrinkling and cracking‐dominant (WCD) mode, and iii) cracking‐dominant (CD) mode. The pressure sensor can exhibit distinct sensing performances for various specific applications, depending on the working mode. In a WD mode, the sensor reveals an ultrahigh sensitivity (≈20 kPa−1) and a low limit of detection (0.6 Pa), capable of sensing acoustic vibrations, subtle pulses, and tiny motions. The sensor in WCD mode can monitor the full‐range human motion from the subtle pulse to human gait during walking/jogging. Moreover, the sensor in CD mode exhibits high sensitivity (1420 MPa−1) and excellent linearity over the ultrahigh pressure range (greater than 20 MPa), and are able to detect the movement of a car and distinguish the embarkation/debarkation of an adult passenger. The underlying mechanisms for the three sensing modes have been clearly elucidated, respectively. These findings open up new possibilities to design flexible pressure sensors by harnessing wrinkling‐cracking architectures.

Dry eye disease (DED) is a multifactorial disease with a high prevalence worldwide. Uncomfortable corneal sensations severely affect daily life in DED patients. Hence, corneal neuron injury is a vital pathogenesis in DED. Notably, endoplasmic reticulum stress (ERS) plays a role in peripheral neuron injury. However, the role of ERS in DED corneal neuron injury is still far from being clear. In this study, we established an environmental DED (eDED) model in vivo and a hyperosmotic DED model in vitro. Subsequently, trigeminal ganglion (TG) corneal neurons were retrograde labeled by WGA-Alexa Fluor 555, and fluorescence-activated cell sorting was used to collect targeted corneal neurons for RNA sequencing in mice. Our results revealed that there is TG corneal neuron injury but not neuron apoptosis in DED. ERS-related genes and proteins were upregulated in TG corneal neurons of the eDED mice. ERS inhibition alleviated TG corneal neuron’s ERS-related injury. Therefore, ERS-induced TG corneal neuron injury may be an important pathomechanism and provide a promising therapeutic approach to DED.

Due to a similar plant morphology in the majority of Zingiberaceae spices, substitution and adulteration frequently take place during the sales process. Therefore, it is important to analyze the metabolites and species classification of different Zingiberaceae spices. This study preliminarily explored the differences in the metabolites in thirteen Zingiberaceae spices through untargeted gas chromatography–mass spectrometry (GC–MS) and combined spectroscopy, establishing models for classifying different Zingiberaceae spices. On one hand, a total of 81 metabolites were successfully identified by GC–MS. Thirty-seven differential metabolites were screened using variable important in projection (VIP ≥ 1). However, the orthogonal partial least squares discriminant analysis (OPLS-DA) model established using GC–MS data only explained about 30% of the variation. On the other hand, the partial least squares discriminant analysis (PLS-DA) models with three spectral data fusion strategies were compared, and their classification accuracy reached 100%. Among them, the mid-level data fusion model based on latent variables had the best performance. This study provides a powerful tool for distinguishing different Zingiberaceae spices and assists in reducing the occurrence of substitution and adulteration phenomena.

Abstract Background At present, hepatectomy is still the most common and effective treatment method for intrahepatic cholangiocarcinoma (ICC) patients. However, the postoperative prognosis is poor. Therefore, the prognostic factors for these patients require further exploration. Whether microvascular invasion (MVI) plays a crucial role in the prognosis of ICC patients is still unclear. Moreover, few studies have focused on preoperative predictions of MVI in ICC patients. Methods Clinicopathological data of 704 ICC patients after curative resection were retrospectively collected from 13 hospitals. Independent risk factors were identified by the Cox or logistic proportional hazards model. In addition, the survival curves of the MVI-positive and MVI-negative groups before and after matching were analyzed. Subsequently, 341 patients from a single center (Eastern Hepatobiliary Hospital) in the above multicenter retrospective cohort were used to construct a nomogram prediction model. Then, the model was evaluated by the index of concordance (C-Index) and the calibration curve. Results After propensity score matching (PSM), Child-Pugh grade and MVI were independent risk factors for overall survival (OS) in ICC patients after curative resection. Major hepatectomy and MVI were independent risk factors for recurrence-free survival (RFS). The survival curves of OS and RFS before and after PSM in the MVI-positive groups were significantly different compared with those in the MVI-negative groups. Multivariate logistic regression results demonstrated that age, gamma-glutamyl transpeptidase (GGT), and preoperative image tumor number were independent risk factors for the occurrence of MVI. Furthermore, the prediction model in the form of a nomogram was constructed, which showed good prediction ability for both the training (C-index = 0.7622) and validation (C-index = 0.7591) groups, and the calibration curve showed good consistency with reality. Conclusion MVI is an independent risk factor for the prognosis of ICC patients after curative resection. Age, GGT, and preoperative image tumor number were independent risk factors for the occurrence of MVI in ICC patients. The prediction model constructed further showed good predictive ability in both the training and validation groups with good consistency with reality.

Background Glycogen synthase kinase 3β (GSK3β) was originally discovered to regulate glycogen synthesis and show a relationship to tumors. However, the biological functions of GSK3β in tumor-associated macrophages (TAMs) in cancers including hepatocellular carcinoma (HCC) remain unclear.Methods The enrichment of GSK3β in tumor tissues was assessed by Gene Expression Omnibus (GEO) database. The in vitro and in vivo assays assisted in evaluating how GSK3β in TAMs affected HCC in terms of proliferation, invasion and migration. Immunofluorescence was used to assess GSK3β expression in TAMs in the anti-PD1 therapy non-responsive HCC group and the responsive group. Western blot and coimmunoprecipitation were performed to demonstrate the interaction between GSK3β and PD-L1. We carried out in vivo experiments in a C57BL/6 mouse model of HCC established through subcutaneous injection.Results GEO single-cell RNA sequencing data suggested that GSK3β was highly enriched in TAMs of HCC. According to in vitro and in vivo experiments, reducing GSK3β in TAMs inhibits the cancer cell proliferation, invasion, and migration. The immunofluorescence and immunohistochemistry results confirmed that the GSK3β is significantly upregulated in TAMs of the anti-PD1 therapy non-responsive group in comparison with the responsive group. In vitro and in vivo experiments confirmed that reduced GSK3β in TAMs are capable of enhancing the sensitivity of anti-PD1 immunotherapy for HCC by decreasing PD-L1 ubiquitination. Mass spectrometry results suggested that high expression of CD14+GSK3β+ in the peripheral blood mononuclear cell (PBMC) can predict non-responsive to anti-PD1 treatment. Moreover, escitalopram is confirmed to act as GSK3β inhibitor that can increase the sensitivity of anti-PD1 immunotherapy for HCC.Conclusions This study revealed that macrophage GSK3β deficiency can inhibit the development of HCC by inhibiting the M2 phenotype and enhance the sensitivity of anti-PD1 immunotherapy for HCC by decreasing PD-L1 ubiquitination. The expression of CD14+GSK3β+ in PBMC can noninvasively predict anti-PD1 sensitivity in HCC patients, which provides novel strategies to predict anti-PD1 sensitivity, increase anti-PD1 therapeutic effect, and bring new hope for HCC patients.

T cells are crucial for controlling viral infections; however, the mechanisms that dampen their responses during viral infections remain incompletely understood. Here, we studied the role and mechanisms of mitochondrial topoisomerase 1 (Top1mt) inhibition in mitochondrial dysfunction and T cell dysregulation using CD4 T cells from patients infected with HCV or HIV and compared it with CD4 T cells from healthy individuals following treatment with Top1 inhibitor - camptothecin (CPT). We found that Top1mt protein levels and enzymatic activity are significantly decreased, along with Top1 cleavage complex (Top1cc) formation, in mitochondria of CD4 T cells from HCV- and HIV-infected patients. Notably, treatment of healthy CD4 T cells with CPT caused similar changes, including inhibition of Top1mt, accumulation of Top1cc in mitochondria, increase in PARP1 cleavage, and decrease in mtDNA copy numbers. These molecular changes resulted in mitochondrial dysfunction, T cell dysregulation, and programmed cell death through multiple signaling pathways, recapitulating the phenotype we detected in CD4 T cells from HCV- and HIV-infected patients. Moreover, treatment of CD4 T cells from HCV or HIV patients with CPT further increased cellular and mitochondrial reactive oxygen species (ROS) production and cell apoptosis, demonstrating a critical role for Top1 in preventing mtDNA damage and cell death. These results provide new insights into the molecular mechanisms underlying immune dysregulation during viral infection and indicate that Top1 inhibition during chronic HCV or HIV infection can induce mtDNA damage and T cell dysfunction. Thus, reconstituting Top1mt protein may restore the mtDNA topology and T cell functions in humans with chronic viral infection.

Triple-negative breast cancer (TNBC) is a heterogeneous and invasive breast cancer (BC) subtype that is estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2 (Her2)-negative. So far, the treatment of TNBC is still ineffective due to the lack of well-defined molecular targets. Exosomes are nanosized extracellular vesicles composed of lipid bilayers. They originate from various types of donor cells and release a complex mixture of contents including diverse nucleic acid types (miRNA, LnRNA, siRNA, and DNA) and proteins; after binding to recipient cells the exosomes release their contents that execute their biological functions. Exosomes have been reported to play an important role in the tumorigenesis of TNBC, including tumor initiation, metastasis, angiogenesis, cell proliferation, immune escape, and drug resistance. On the other hand, exosomes can be valuable biomarkers for diagnosis, monitoring, and treatment of TNBC. More interestingly, exosomes can be harnessed as a nanosized drug-delivery system specifically targeting TNBC. In this review, we present the most recent mechanistic findings and clinical applications of exosomes in TNBC therapy, focusing on their use as diagnostic and prognostic biomarkers, nanoscale drug delivery platforms, and immunotherapeutic agents. In addition, the associated challenges and future directions of using exosomes for TNBC treatment will be discussed.

Abstract Amomum tsao-ko, as an edible and medicinal variety, has been cultivated for more than 600 years in China. Recently, two cultivars, A. tsao-ko and Amomum paratsao-ko, were found in A. tsao-ko planting area. The two cultivars are often confused because of the similar phenotype and difficult to distinguish through sensory judgment. In this study, the non-targeted gas chromatography-mass spectrometry (GC–MS) metabolomics combined with near-infrared spectroscopy (NIRS) were used for dissecting the two cultivars with phenotypic differences. According to principal component analysis (PCA) loading diagram and orthogonal partial least squares discriminant analysis (OPLS-DA) S-plot of the metabolites, the accumulation of major components including 1,8-cineole, α-phellandrene, (E)-2-decenal, (−)-β-pinene, (E)-2-octenal, 1-octanal, D-limonene, and decanal, were present differences between the two cultivars. Seven metabolites potential differentiated biomarkers as β-selinene, decamethylcyclopentasiloxane, (E,Z)-2,6-dodecadienal, (E)-2-hexenal, (E)-2-decenal, isogeranial, 1,8-cineole and β-cubebene were determined. Although A. tsao-ko and A. paratsao-ko belong to the same genera and are similar in plant and fruit morphology, the composition and content of the main components were exposed significant discrepancy, so it is necessary to distinguish them. In this study, the discriminant model established by GC–MS or NIRS combined with multivariate analysis has achieved a good classification effect. NIRS has the advantages of simple, fast and nondestructive and can be used for rapid identification of varieties and fruit tissues.

Assessing fault activity in regions lacking Quaternary sedimentary constraints remains a global challenge. In this study, we used channel slope distribution to examine variations in rock uplift along faults. By comparing channel steepness with published low-temperature thermochronology and paleo-seismic data, we identified deformation changes both perpendicular to and along the Longmen Shan at various time scales. Our data revealed distinct fault segments displaying distinct thrust activities along the Longmen Shan’s strike. In the southern segment, the Dachuan fault exhibited the highest activity, and its movement had persisted for millions of years. In the central segment, the Wenchuan fault was active during theearly Quaternary but has become dormant since the late Pleistocene. Within the past millions of years, the Yingxiu and Pengguan faults displayed significant vertical displacement. Fault activity in the northern Longmen Shan was relatively weak, with the Qingchuan fault transitioning from thrust movement during the Neogene to pure strike-slip activity since the Pleistocene. Overall, the Dachuan and Huya faults exhibited deformation patterns similar to the Yingxiu fault during the Quaternary. Similar to the Yingxiu fault, which triggered the Wenchuan earthquake, the Dachuan and Huya faults possess the capacity to produce significant earthquakes in the future. The variations in deformation perpendicular to and along the Longmen Shan fault system underscore the importance of upper crustal shortening in shaping the rock uplift patterns and topography of the eastern Tibetan Plateau margin.

Phytocyanins (PCs), plant-specific blue copper proteins, are crucial for various biological processes during plant development. However, a comprehensive characterization of the soybean PC gene family (GmPC) is lacking. In this study, we performed genome-wide screening of soybean PC genes, and 90 PC genes were identified in the soybean genome. Further analysis revealed that the GmPC family was categorized into four subfamilies (stellacyanins, GmSCs; uclacyanins, GmUCs; plantacyanins, GmPLCs; and early nodulin-like proteins, GmENODLs). In-depth analysis revealed that each specific GmPC subfamily exhibited similar characteristics, with segmental duplications playing a major role in expanding the members of GmPC. Additionally, synteny and evolutionary constraint analyses suggested that GmPCs have undergone strong selective pressure for purification during the evolution of soybeans. The promoter cis-regulatory elements analysis of GmPCs suggested that GmPCs might play a crucial role in various stress responses. The expression patterns of GmPCs exhibited tissue-specific variations. Moreover, 23 of the GmPCs may be involved in soybean’s response to salt stress. In all, our study presents a systematic overview of GmPC, which not only provides a valuable foundation for further functional investigations of GmPCs, but also offers new insights into the mechanism of soybean salt tolerance.

Abstract Background Phosphorus (P) is essential for plant growth and development, and low-phosphorus (LP) stress is a major factor limiting the growth and yield of soybean. Long noncoding RNAs (lncRNAs) have recently been reported to be key regulators in the responses of plants to stress conditions, but the mechanism through which LP stress mediates the biogenesis of lncRNAs in soybean remains unclear. Results In this study, to explore the response mechanisms of lncRNAs to LP stress, we used the roots of two representative soybean genotypes that present opposite responses to P deficiency, namely, a P-sensitive genotype (Bogao) and a P-tolerant genotype (NN94156), for the construction of RNA sequencing (RNA-seq) libraries. In total, 4,166 novel lncRNAs, including 525 differentially expressed (DE) lncRNAs, were identified from the two genotypes at different P levels. GO and KEGG analyses indicated that numerous DE lncRNAs might be involved in diverse biological processes related to phosphate, such as lipid metabolic processes, catalytic activity, cell membrane formation, signal transduction, and nitrogen fixation. Moreover, lncRNA-mRNA-miRNA and lncRNA-mRNA networks were constructed, and the results identified several promising lncRNAs that might be highly valuable for further analysis of the mechanism underlying the response of soybean to LP stress. Conclusions These results revealed that LP stress can significantly alter the genome-wide profiles of lncRNAs, particularly those of the P-sensitive genotype Bogao. Our findings increase the understanding of and provide new insights into the function of lncRNAs in the responses of soybean to P stress.

Abstract It is difficult to improve the curative effects of cancer immunotherapy on solid tumors. Cytokines, as powerful immune regulators, show potential in activating host antitumor immunity. We have previously found that the administration of certain cytokine combinations induces complete tumor clearance. Here, we constructed cognate fusion cytokines and evaluated their antitumor effects in various mouse tumor models. The in situ induction of the expression of the fusion cytokine IL12IL2GMCSF caused tumor eradication, including that of the tumors at advanced stages. An immune memory against unrelated syngeneic tumors was also elicited. Furthermore, flow cytometry analysis revealed that tumor‐infiltrating CD3+ cells were greatly increased in the treated tumors and were accompanied by an elevation of CD8+/CD4+ ratios. This fusion protein exhibited superior immune activating capability compared to that of cytokine mixtures, in the experiments done in vitro. We also induced tumor regression in various immunocompetent tumor models via intratumoral injection. To improve its translational potential for clinical application, a systemically‐administered immunocytokine, IL12IL2DiaNFGMCSF, was constructed by inserting a tumor‐targeting diabody in the fusion protein. This protein also displayed good immune stimulating activities in vitro. Intravenous infusion of IL12IL2DiaNFGMCSF induced tumor‐infiltrating immune cell alterations like IL12IL2GMCSF, with moderate serum IFNγ increment. Therapeutic effects were observed in the various tumor models after systemic administration of IL12IL2DiaNFGMCSF, but with slight toxicity. These results show the feasibility of developing a versatile cancer immunotherapy.

Apolipoprotein E (APOE) gene encodes three protein isoforms (APOEε-22/ε-33/ε-44), which governs the transportation and metabolism of lipoproteins differently. While abnormalities in lipid and lipoprotein metabolism have been identified as risk factors for type 2 diabetes mellitus (T2DM). APOE gene polymorphisms might be correlated with increased risk of T2DM. Therefore, we presented an iPSC line harboring an APOE-ε3/ε3 alleles, a male donor suffering from T2DM combined with Hypertension. The derived iPSCs showed pluripotency, the capacity to differentiate into three germ layers, and normal karyotypes. Collectively, the present study provides a useful resource to reveal the associated mechanism of APOE isoform and T2DM.

Cancer is one of the most frequently diagnosed malignant diseases worldwide, posing a serious, long-term threat to patients’ health and life. Systemic chemotherapy remains the first-line therapeutic approach for recurrent or metastatic cancer patients after surgery, with the potential to effectively extend patient survival. However, the development of drug resistance seriously limits the clinical efficiency of chemotherapy and ultimately results in treatment failure and patient death. A large number of studies have shown that non-coding RNAs (ncRNAs), particularly microRNAs, long non-coding RNAs, and circular RNAs, are widely involved in the regulation of cancer drug resistance. Their dysregulation contributes to the development of cancer drug resistance by modulating the expression of specific target genes involved in cellular apoptosis, autophagy, drug efflux, epithelial-to-mesenchymal transition (EMT), and cancer stem cells (CSCs). Moreover, some ncRNAs also possess great potential as efficient, specific biomarkers in diagnosis and prognosis as well as therapeutic targets in cancer patients. In this review, we summarize the recent findings on the emerging role and underlying mechanisms of ncRNAs involved in cancer drug resistance and focus on their clinical applications as biomarkers and therapeutic targets in cancer treatment. This information will be of great benefit to early diagnosis and prognostic assessments of cancer as well as the development of ncRNA-based therapeutic strategies for cancer patients.

Abstract The recent COVID-19 pandemic poses a serious threat to global public health, thus there is an urgent need to define the molecular mechanisms involved in SARS-CoV-2 spike (S) protein-mediated virus entry that is essential for preventing and/or treating this emerging infectious disease. In this study, we examined the blocking activity of human COVID-19 convalescent plasma by cell–cell fusion assays using SARS-CoV-2-S-transfected 293 T as effector cells and ACE2-expressing 293 T as target cells. We demonstrate that the SARS-CoV-2 S protein exhibits a very high capacity for membrane fusion and is efficient in mediating virus fusion and entry into target cells. Importantly, we find that COVID-19 convalescent plasma with high titers of IgG neutralizing antibodies can block cell–cell fusion and virus entry by interfering with the SARS-CoV-2-S/ACE2 or SARS-CoV-S/ACE2 interactions. These findings suggest that COVID-19 convalescent plasma may not only inhibit SARS-CoV-2-S but also cross-neutralize SARS-CoV-S-mediated membrane fusion and virus entry, supporting its potential as a preventive and/or therapeutic agent against SARS-CoV-2 as well as other SARS-CoV infections.

High-strength titanium (Ti) alloys are progressively demanded for structural applications in weight-critical aerospace industry. Improving mechanical properties of the alloys are thus exploited in response to the requirement. In this study, a strategy of through-transus thermomechanical forging was applied to the Ti–10 V–2Fe–3Al metastable β-Ti alloy, and the resulting microstructures and mechanical properties were systematically investigated in comparison to the conventional (α+β) dual-phase field forging. It is found that the through-transus thermomechanical forging significantly enhances strength, ductility and strain hardening capacity, while it is the inferior combinations of mechanical properties in the alloys subjected to the (α+β) dual-phase field forging. Microstructural characterization reveals that the former renders the hierarchical microstructure composed of intergranular αp-necklaces, and intragranular αp-rods as well as αs-lamellae in the β-matrix. The superior combinations of mechanical properties are conferred by good strain compatibility of these microstructural constituents. By contrast, the latter renders the network microstructure comprised of intergranular globular αp-phase and continuous grain boundary (GB) αGB-films as well as the intragranular αs-lamellae. Local deformation-damage is more preferred to initiate in the intergranular network structure. These findings provide fundamental understanding on the correlation between mechanical properties and microstructures, facilitating manufacturing high-performance β-Ti alloys at an industry scale using commercially available thermomechanical processing.

Abstract HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) is a long non-coding RNA (lncRNA) that plays a pivotal role in regulating myeloid cell development via targeting HOXA1 gene expression. We and others have previously shown that myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature myeloid cells, expand during chronic viral (HCV, HIV) infections. However, the role of HOTAIRM1 in the development and suppression of MDSCs during viral infection remains unknown. In this study, we demonstrate that the expressions of HOTAIRM1 and its target HOXA1 are substantially upregulated to promote the expressions of immunosuppressive molecules, including arginase 1, inducible nitric oxide synthase, signal transducer and activator of transcription 3, and reactive oxygen species, in CD33+ myeloid cells derived from hepatitis C virus (HCV)-infected patients. We show that HCV-associated exosomes (HCV-Exo) can modulate HOTAIRM1, HOXA1, and miR124 expressions to regulate MDSC development. Importantly, overexpression of HOTAIRM1 or HOXA1 in healthy CD33+ myeloid cells promoted the MDSC differentiation and suppressive functions; conversely, silencing of HOTAIRM1 or HOXA1 expression in MDSCs from HCV patients significantly reduced the MDSC frequency and their suppressive functions. In essence, these results indicate that the HOTAIRM1-HOXA1-miR124 axis enhances the differentiation and suppressive functions of MDSCs and may be a potential target for immunomodulation in conjunction with antiviral therapy during chronic viral infection.

Abstract Background Heroin dependence is a complex disease with multiple phenotypes. Classification of heroin users into more homogeneous subgroups on the basis of these phenotypes could help to identify the involved genetic factors and precise treatments. This study aimed to identify the association between genetic polymorphisms of DA synthesis and metabolism genes, including tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), solute carrier family 6 member 3 (SLC6A3) and DA beta-hydroxylase (DBH), with six important phenotypes of heroin dependence. Methods A total of 801 heroin dependent patients were recruited and fourteen potential functional single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot. Associations between SNPs with six phenotypes were mainly assessed by binary logistic regression. Generalized multifactor dimensionality reduction was used to analyze the gene-by-gene and gene-by-environment interactions. Results We found that DBH rs1611114 TT genotype had a protective effect on memory impairment after heroin dependence (P = 0.002, OR = 0.610). We also found that the income-rs12666409-rs129915-rs1611114 interaction yielded the highest testing balance accuracy and cross-validation consistency for memory change after heroin dependence. Conclusions Our results suggest that the memory change after heroin dependence was a result of a combination of genetics and environment. This finding could lead to a better understanding of heroin dependence and further improve personalized treatment.

ObjectivesOccupational exposure to carcinogens is associated with trachea, bronchus, and lung (TBL) cancer. The objective of this study was to provide global and regional estimates of the burden of TBL cancer associated with occupational carcinogens (OCs) between 1990 and 2019.MethodsAge-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years (DALYs) rates (ASDR) of TBL cancer related to exposure to OCs at the global and regional levels were extracted for 1990–2019 from the Global Burden of Disease 2019. Joinpoint regression was used to analyze trends in the ASMR and ASDR of TBL cancer burden related to OCs, and the annual percent change and the average annual percent change (AAPC) were recorded.ResultsThe mortality from TBL cancer related to exposure to OCs increased globally. The ASMR and ASDR decreased in both sexes and in men between 1990 and 2019. The AAPC of ASMR and ASDR decreased in men between 1990 and 2019, but increased in women. Asbestos accounted for the highest death number and beryllium accounted for the lowest; diesel engine exhaust caused the largest percentage change in death number (145.3%), in ASDR (14.9%), and in all ages DALY rates (57.6%). Asbestos accounted for the largest death number in high social development index (SDI) countries, whereas low-middle SDI countries had the largest percent change (321.4%). Asbestos was associated with decreased ASDR in high SDI countries and increased ASDR in low-middle SDI countries, and similar changes were observed for other OCs.ConclusionsThe overall mortality and DALYs of TBL cancer burden related to OCs showed a decreasing trend between 1990 and 2019, whereas death number increased. Asbestos accounted for the highest death number. TBL cancer burden related to OCs decreased to different degrees in high, low, low-middle, and middle SDI countries, which showed variable levels of TBL cancer burden related to exposure to OCs (except asbestos).

The ε4 allele of the Apolipoprotein E gene (APOE4) continues to be the strongest genetic risk factor associated with sporadic Alzheimer’s disease since its discovery compared to the most common ε3 allele. Nevertheless, there is a lack of APOE4-mutant human neuronal models in vitro or in vivo. Hence, we presented an iPSC line of an APOE-ε4/ε4 alleles carrier, a male donor suffering from Alzheimer’s disease combined with cerebral infarction. The established iPSC line showed standard characteristics of pluripotency. Collectively, the present study provides a useful resource to reveal the phenotype and explore the mechanism of APOE4 related Alzheimer’s disease.

Work analysis is one of critical tools for improving order picking efficiency in logistics centers. Traditionally, video analysis has been used to analyze work time for various tasks. However, video analysis generally requires a substantial amount of time and labor, which makes it too inefficient for real-time work improvement. To address this, a novel automatic work analysis method is proposed for analyzing the order picking process in logistics centers in this study. The automatic work analysis method can be divided into two parts: dynamic positioning and motion analysis. With the proposed method, an ultrasonic network and a tracking camera are used for measuring a worker’s real-time position while he/she is moving, and an acceleration sensor is used for checking the acceleration of the dominant working hand. Using the position and acceleration data, the worker’s motion is then estimated by an estimation model pre-tested for accuracy. To test the effectiveness of the proposed method, an experiment was conducted in which the measurement error of positioning was found to be approximately 0.01±0.19 m for the x-coordinate values and 0.03±0.45 m for the y-coordinate values. The total measurement error was confirmed to be within a one-step stride. The results of the motion analysis were more than 90% consistent with those obtained by traditional video analysis.

We have previously demonstrated mitochondrial dysfunction in aging CD4 T cells from antiretroviral therapy (ART)-controlled people living with HIV (PLWH). However, the underlying mechanisms by which CD4 T cells develop mitochondrial dysfunction in PLWH remain unclear. In this study, we sought to elucidate the mechanism(s) of CD4 T cell mitochondrial compromise in ART-controlled PLWH. We first assessed the levels of reactive oxygen species (ROS), and we observed significantly increased cellular and mitochondrial ROS levels in CD4 T cells from PLWH compared to healthy subjects (HS). Furthermore, we observed a significant reduction in the levels of proteins responsible for antioxidant defense (superoxide dismutase 1, SOD1) and ROS-mediated DNA damage repair (apurinic/apyrimidinic endonuclease 1, APE1) in CD4 T cells from PLWH. Importantly, CRISPR/Cas9-mediated knockdown of SOD1 or APE1 in CD4 T cells from HS confirmed their roles in maintaining normal mitochondrial respiration via a p53-mediated pathway. Reconstitution of SOD1 or APE1 in CD4 T cells from PLWH successfully rescued mitochondrial function as evidenced by Seahorse analysis. These results indicate that ROS induces mitochondrial dysfunction, leading to premature T cell aging via dysregulation of SOD1 and APE1 during latent HIV infection.

Ural blocking high (hereafter UB) is one of the most important weather systems influencing the weather and climate of China, with its onset and development closely connected with transient eddies. Herein, we classified the wintertime UB events during 1979–2015 into three types according to their lifetime, i.e., short, medium, and long lifetime UB events and further analyzed the characteristics of momentum and heat fluxes transported by transient eddies during the three types of UB events. The results show that the eddy momentum and heat transport by transient eddies over the Ural regions is strong, while the westerly is weak, favorable for the establishment and maintenance of the UB. Before the onset of all the UB events there are enhanced lower-level temperature disturbances, decelerated westerly and convergence of transient momentum and heat fluxes. After the onset of the UB, the upper-level jet stream is accelerated and eddy flux convergence is enhanced. Furthermore, it is found that the duration and position of convergence could be one of important factors determining the lifetime of UB event. The long-time strong convergence of transient eddies favors the maintenance of UB. During long UB events, the polar jet and the convergence of eddy momentum fluxes have the strongest intensity and northward shifted position. The convergence is further strengthened until Day +2 and weakened since Day +7, favorable for the long-time maintenance of UB. There is convergence on Day -3 of both short and medium UB events, which disappears on Day +4 during short events, while strengthened after the onset of medium events, leading to a long-time maintenance of UB. Furthermore, among the three types of UB events, the upward propagation of wave activity and E-P flux divergence are the strongest and most long-lasting during long UB events, while the weakest and shortest during short UB events, which can also verify strong atmospheric baroclinicity and long-lasting strong convergence of transient eddies are favorable for long duration of the UB.