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Summary: Polarity proteins regulate the proliferation and differentiation of neural progenitors to generate neurons during brain development through multiple signaling pathways. However, how cell polarity couples the signaling pathways remains unclear. Here, we show that coiled-coil domain-containing protein 85c (Ccdc85c) interacts with the polarity protein Par3 to regulate the proliferation of radial glial cells (RGCs) via phase separation coupled to percolation (PSCP). We find that the interaction with Ccdc85c relieves the intramolecular auto-inhibition of Par3, which leads to PSCP of Par3. Downregulation of Ccdc85c causes RGC differentiation. Importantly, the open conformation of Par3 facilitates the recruitment of the Notch regulator Numb to the Par3 condensates, which might prevent the attenuation of Notch activity to maintain RGC proliferation. Furthermore, ectopic activation of Notch signaling rescues RGC proliferation defects caused by the downregulation of Ccdc85c. These results suggest that Ccdc85c-mediated PSCP of Par3 regulates Notch signaling to control RGC proliferation during brain development.

The rapid development of wearable electronics has stimulated the urgent demand for compatible, miniaturized energy storage devices. As one of the most promising candidates, micro-supercapacitors (MSCs) have attracted significant attention, owing to their high power densities, long operation life, and fast charge/discharge rate. In comparison to conventional, rigid MSCs, deformable MSCs are attracting more and more attention for their superior tolerance to various deformations, including stretching, bending, and twisting, guaranteeing smooth operation of the wearable electronics. MXenes, a class of emerging two-dimensional transition metal carbonitrides/nitrides, have metallic conductivity, high specific surface area, good hydrophilicity, and surface chemical tunability, showing great potential as electrode material for MSCs. In this paper, the recent progress, focused on the MXene-based, stretchable MSCs with fiber-shaped, planar configuration, is systematically summarized. Moreover, the key challenges and prospects of MXene-based, stretchable MSCs for practical application are discussed, which are critical for further development of them.

ABSTRACT The gut flora is a treasure house of diverse bacteriophages maintaining a harmonious and coexistent relationship with their hosts. The giant panda (Ailuropoda melanoleuca), as a vulnerable endemic species in China, has existed for millions of years and is regarded as a flagship species for biodiversity conservation. And yet, limited studies have analyzed the phage communities in the gut of giant pandas. Using viral metagenomic analysis, the phageomes of giant pandas and other relative species were investigated. Our study explored and compared the composition of phage communities from different animal sources. Giant pandas possessed more diverse and abundant phage communities in the gut compared with other relevant animals. Phylogenetic analyses based on the phage terminase large subunit (TerL) showed that the Caudovirales phages in giant pandas also presented highly genetic diversity. Our study revealed the diversity of phage communities in giant pandas and other relative species, contributing to the health maintenance of giant pandas and laying the groundwork for molecular evolution research of bacteriophages in mammals. IMPORTANCE Gut phageome plays an important role in shaping gut microbiomes by direct interactions with bacteria or indirect influences on the host immune system, potentially regulating host health and disease status. The giant panda (Ailuropoda melanoleuca) is a vulnerable and umbrella species for biodiversity conservation. Our work explored and compared the gut phageome of giant pandas and relative species, contributing to the health maintenance of giant pandas.

Starch is an essential factor affecting the quality of flue-cured tobacco, and high starch content can affect the sensory quality and safety. Recently, the degradation of macromolecules in tobacco raw materials by using additional microorganisms to improve their intrinsic quality and safety has become a new research hotspot in the tobacco industry. However, the technical maturity and application scale are limited. Our study analyzed the correlation between microbial community composition and volatile components on the surface of tobacco leaves from 14 different grades in Fujian tobacco-producing areas. The PICRUSt software was utilized to predict the function of the microbial community present in tobacco leaves. Furthermore, dominant strains that produced amylase were screened out, and an enzyme solution was prepared to enhance the flue-cured tobacco flavor. Changes in the content of macromolecules and volatile components were determined, and sensory evaluations were conducted to assess the overall quality of the tobacco leaves. The results showed that the dominant bacterial genera on the surface of Fujian tobacco leaves were Variovorax, Sphingomonas, Bacillus, etc. Bacillus was positively correlated with various volatile components, which contributed to the sweet and aromatic flavors of Fujian flue-cured tobacco. The main genetic functions of Fujian flue-cured tobacco surface bacteria were carbohydrate metabolism and amino acid metabolism. After treating flue-cured tobacco with an enzyme preparation prepared by the fermentation of Paenibacillus amylolyticus A17 #, the content of starch, pectin, and cellulose in flue-cured tobacco decreased significantly compared with the control group. Meanwhile, the content of total soluble sugar and reducing sugar was significantly increased, and the volatile aroma components, such as 3-hydroxy--damascone, 2,3-dihydro-3,5-dihydroxy-6-methyl-4 H-Pyran-4-one, ethyl palmitate, ethyl linolenic acid, etc., were significantly increased. The aroma quality and quantity of flue-cured tobacco were enhanced, while impurities were reduced. The smoke characteristics were improved, with increased fineness, concentration, and moderate strength. The taste characteristics were also improved, with reduced irritation and a better aftertaste. In conclusion, Bacillus, as the dominant genus in the abundance of bacterial communities on tobacco surfaces in Fujian, had an essential impact on the flavor of tobacco leaves by participating in carbohydrate metabolism and finally forming the unique flavor style of flue-cured tobacco in Fujian tobacco-producing areas. Paenibacillus amylolyticus A17 #, a target strain with amylase-producing ability, was screened from the surface of Fujian flue-cured tobacco. The enzyme preparation, produced by the fermentation of Paenibacillus amylolyticus A17 #, was utilized to reduce the content of macromolecules, increase the content of water-soluble total sugar and reducing sugar, and produce a variety of crucial volatile aroma components, which had a significant improvement on the quality of tobacco leaves.

Viral diseases caused by new outbreaks of viral infections pose a serious threat to human health. Wild brown rats (Rattus norvegicus), considered one of the world's largest and most widely distributed rodents, are host to various zoonotic pathogens. To further understand the composition of the virus community in wild brown rats and explore new types of potentially pathogenic viruses, viral metagenomics was conducted to investigate blood, feces, and various tissues of wild brown rats captured from Zhenjiang, China. Results indicated that the composition of the virus community in different samples showed significant differences. In blood and tissue samples, members of the Parvoviridae and Anelloviridae form the main body of the virus community. Picornaviridae, Picobirnaviridae, and Astroviridae made up a large proportion of fecal samples. Several novel genome sequences from members of different families, including Anelloviridae, Parvoviridae, and CRESS DNA viruses, were detected in both blood and other samples, suggesting that they have the potential to spread across organs to cause viremia. These viruses included not only strains closely related to human viruses, but also a potential recombinant virus. Multiple dual-segment picornaviruses were obtained from fecal samples, as well as virus sequences from the Astroviridae and Picornaviridae. Phylogenetic analysis showed that these viruses belonged to different genera, with multiple viruses clustered with other animal viruses. Whether they have pathogenicity and the ability to spread across species needs further study.

ABSTRACT Aquaculture is important for food security and nutrition. The economy has recently been significantly threatened and the risk of zoonoses significantly increased by aquatic diseases, and the ongoing introduction of new aquatic pathogens, particularly viruses, continues to represent a hazard. Yet, our knowledge of the diversity and abundance of fish viruses is still limited. Here, we conducted a metagenomic survey of different species of healthy fishes caught in the Lhasa River, Tibet, China, and sampled intestinal contents, gills, and tissues. To be more precise, by identifying and analyzing viral genomes, we aim to determine the abundance, diversity, and evolutionary relationships of viruses in fish with other potential hosts. Our analysis identified 28 potentially novel viruses, 22 of which may be associated with vertebrates, across seven viral families. During our research, we found several new strains of viruses in fish, including papillomavirus, hepadnavirus, and hepevirus. Additionally, we discovered two viral families, Circoviridae and Parvoviridae, which were prevalent and closely related to viruses that infect mammals. These findings further expand our understanding of highland fish viruses and highlight the emerging view that fish harbor large, unknown viruses. IMPORTANCE The economy and zoonoses have recently been significantly threatened by aquatic diseases. Yet, our knowledge of the diversity and abundance of fish viruses is still limited. We identified the wide genetic diversity of viruses that these fish were harboring. Since there are currently few studies on the virome of fish living in the Tibet highland, our research adds to the body of knowledge. This discovery lays the groundwork for future studies on the virome of fish species and other highland animals, preserving the ecological equilibrium on the plateau.

Vegetation restoration has become a common practice in karst rocky desertification (KRD) areas of southwestern China. The bacteria, which have made a connection between soil and plants, have been an important role in regulating the succession and restoration of karst vegetation. However, it is still unclear how soil bacterial communities and soil properties respond to natural vegetation restoration processes in karst areas. To address this gap, we investigated the soil nutrients, enzyme activity, and soil bacterial community among various plant communities, including farmland (FL), land with herbs only (SSI), herb-and-shrub land (SSII), woody thickets (SSIII), coniferous forest (SSIV), coniferous and broad-leaved mixed forest (SSV), and evergreen broad-leaved forest (SSVI). Our results found that SSII had the highest levels of soil organic matter, total nitrogen, available phosphorus, available nitrogen, sucrase, and β-glucosidase among all the plant communities. These results indicated that herb-and-shrub land have contributed to the rapid restoration of vegetation in KRD regions. FL exhibited the lowest levels of soil nutrients and enzyme activities, while showing the highest bacterial richness and diversity among all the plant communities. This suggested that appropriate human intervention can increase bacterial diversity and richness in the area. The predominant bacterial phylum also varied among the different plant communities, with Actinobacteria being the most abundant in SSI, SSII, SSIII, and SSIV, while Proteobacteria were the most abundant in SSV and SSVI. Furthermore, PCoA analysis demonstrated significant changes in the soil bacterial community structure, with SSI, SSII, SSIII, and SSIV had shared similar structures, while SSV and SSVI had comparable structures. As for soil characteristics, total phosphorus (TP) and total potassium (TK) were the primary factors affecting the soil bacterial community. SSV and SSVI had the most complex bacterial networks and were more stable than other groups. The genera Ktedonobacter, norank_f_Anaerolineaceae, and Vicinamibacter had the highest betweenness centrality scores and were identified as keystone genera in the co-occurrence network in KRD areas. In summary, our results have demonstrated that herb-and-shrub can promote community succession and increase soil nutrient levels in KRD regions.

IntroductionThe escalating incidence of Crohn’s disease (CD), a debilitating ailment that ravages individuals and their families, has become a formidable issue over recent decades.MethodIn this study, fecal samples from patients with CD and healthy individuals were investigated by means of viral metagenomics.ResultsThe fecal virome was analyzed and some suspected disease-causing viruses were described. A polyomavirus named HuPyV with 5,120 base pairs (bp) was found in the disease group. In a preliminary analysis employing large T region-specific primers, it was found that HuPyV was present in 3.2% (1/31) of healthy samples and 43.2% (16/37) of disease samples. Additionally, two other viruses from the anellovirus and CRESS-DNA virus families were found in fecal samples from CD patients. The complete genome sequences of these two viruses were described respectively, and the phylogenetic trees have been built using the anticipated amino acid sequences of the viral proteins.DiscussionFurther research is required to elucidate the relationship between these viruses and the onset and development of Crohn’s disease.

The role of chemokines in predicting the prognosis of colon cancer has not been mentioned. Chemokines have been shown to be associated with immune cell chemotaxis and activation, so the expression of chemokine genes in tumor tissue may be related to prognosis. We used a least absolute shrinkage and selection operator (LASSO) model based on chemokine gene families to construct a model that can predict the prognosis of colon cancer patients. We divided patients into high-risk groups and low-risk groups to study the prognosis. Then, we evaluated the relationship between the different risk groups in infiltration of immune cells. It was found that there was less immune cell infiltration in the high-risk group. We conducted a functional enrichment analysis based on model stratification, and explored the biological signal pathways enriched in the high and low-risk groups, which provided ideas for studying the mechanism behind its impact on prognosis. In addition, the chemokine-related gene signature could predict the response of patients to immunotherapy and chemotherapy.

As social animals, humans are unique to make the world function well by developing, maintaining, and enforcing social norms. As a prerequisite among these norm-related processes, learning social norms can act as a basis that helps us quickly coordinate with others, which is beneficial to social inclusion when people enter into a new environment or experience certain sociocultural changes. Given the positive effects of learning social norms on social order and sociocultural adaptability in daily life, there is an urgent need to understand the underlying mechanisms of social norm learning. In this article, we review a set of works regarding social norms and highlight the specificity of social norm learning. We then propose an integrated model of social norm learning containing three stages, i.e., pre-learning, reinforcement learning, and internalization, map a potential brain network in processing social norm learning, and further discuss the potential influencing factors that modulate social norm learning. Finally, we outline a couple of future directions along this line, including theoretical (i.e., societal and individual differences in social norm learning), methodological (i.e., longitudinal research, experimental methods, neuroimaging studies), and practical issues.

Summary: The immune-genetic changes that occur in cancer patients experiencing hyperprogressive disease (HPD) during combined immunotherapy are unclear. In this study, HPD patients with pre- and post-HPD samples and non-HPD patients with solid tumors were molecularly characterized by genetic and tumor immune microenvironment (TiME) analyses of paired samples by whole-exome sequencing, RNA sequencing, and multiplex immunofluorescence. The genetic analysis of paired samples showed that almost all the tumor driver gene mutations were preserved between pre- and post-HPD tumors. HPD patients had higher frequencies of mutations in TP53 and CNN2, and a significantly higher mutant-allele tumor heterogeneity than non-HPD patients. Tumor IL-6 mRNA was upregulated in post-HPD samples vs. pre-HPD, accompanied by a potential immune suppressive TiME with an elevated M2/M1 ratio. Salvage treatment with irinotecan plus bevacizumab was effective in one HPD patient, who experienced prolonged survival. These genetic features and TiME characteristics might help identify the features of HPD after immunotherapy.

High-entropy alloys (HEAs) attract much attention as possible radiation-resistant materials due to their several unique properties. In this work, the generation and evolution of the radiation damage response of an FeNiCrCoCu HEA and bulk Ni in the early stages were explored using molecular dynamics (MD). The design, concerned with investigating the irradiation tolerance of the FeNiCrCoCu HEA, encompassed the following: (1) The FeNiCrCoCu HEA structure was obtained through a hybrid method that combined Monte Carlo (MC) and MD vs. the random distribution of atoms. (2) Displacement cascades caused by different primary knock-on atom (PKA) energy levels (500 to 5000 eV) of the FeNiCrCoCu HEA vs. bulk Ni were simulated. There was almost no element segregation in bulk FeNiCrCoCu obtained with the MD/MC method by analyzing the Warren–Cowley short-range order (SRO) parameters. In this case, the atom distribution was similar to the random structure that was selected as a substrate to conduct the damage cascade process. A mass of defects (interstitials and vacancies) was generated primarily by PKA departure. The number of adatoms grew, which slightly roughened the surface, and the defects were distributed deeper as the PKA energy increased for both pure Ni and the FeNiCrCoCu HEA. At the time of thermal spike, one fascinating phenomenon occurred where the number of Frenkel pairs for HEA was more than that for pure Ni. However, we obtained the opposite result, that fewer Frenkel pairs survived in the HEA than in pure Ni in the final state of the damage cascade. The number and size of defect clusters grew with increasing PKA energy levels for both materials. Defects were suppressed in the HEA; that is to say, defects were “cowards”, behaving in an introverted manner according to the anthropomorphic rhetorical method.

In order to investigate the effect of Ti element content on the microstructure and wear resistance of AlCrCuFeNiTi _x (x = 0, 0.3, 0.6, 0.9) high entropy surfacing alloy, a melting electrode gas shielded welding technology was used to prepare AlCrCuFeNiTi _x high entropy surfacing alloy on the surface of carbon steel plates. The microstructure, phase composition, and wear resistance of the alloy were analyzed. The results show that the phase composition of the surfacing alloy becomes a BCC+FCC solid solution phase, with a much higher content of BCC phase than FCC phase. The microstructure consists of disordered BCC phase rich in Fe and Cr, ordered BCC phase rich in Al and Ni, and FCC phase rich in Cu. The microstructure exhibits typical dendritic (DR) and interdendritic (ID) structures. With the increase of Ti element, hard Fe _2 Ti phase precipitates in the interdendritic zone, and the micro hardness of the alloy shows an increasing trend. The maximum hardness can reach 636 HV, which is 2.4 times that of the base material. With the increase of Ti element, the friction coefficient of the alloy shows a trend of first decreasing and then increasing, and the wear amount first decreases and then increases. When Ti is 0.6, the wear resistance of the high entropy surfacing alloy reaches its best.

The growing distributed energy resource (DER) penetration into distribution networks, such as through residential and commercial photovoltaics (PV), has emerged through a transition from passive to active networks, which takes the complexity of planning and operations to the next level. Optimal PV allocation (sizing and location) is challenging because it involves mixed-integer non-linear programming with three-phase non-linear unbalanced power flow equations. Meta-heuristic algorithms have proven their effectiveness in many complex engineering problems. Thus, in this study, we propose to achieve optimal PV allocation by using several basic evolutionary algorithms (EAs), particle swarm optimization (PSO), artificial bee colony (ABC), differential evolution (DE), and their variants, all of which are applied for a study of their performance levels. Two modified unbalanced IEEE test feeders (13 and 37 bus) are developed to evaluate these performance levels, with two objectives: one is to maximize PV penetration, and the other is to minimize the voltage deviation from 1.0 p.u. To handle the computational burden of the sequential power flow and unbalanced network, we adopt an efficient iterative load flow algorithm instead of the commonly used and yet highly simplified forward–backward sweep method. A comparative study of these basic EAs shows their general success in finding a near-optimal solution, except in the case of the DE, which is known for solving continuous optimization problems efficiently. From experiments run 30 times, it is observed that PSO-related algorithms are more efficient and robust in the maximum PV penetration case, while ABC-related algorithms are more efficient and robust in the minimum voltage deviation case.

Resin-based dental materials have been one of the ideal choices among various materials in the treatment of dental caries. However, resin-based dental materials still have some drawbacks, such as the lack of inherent antibacterial activity. Extensive research has been conducted on the use of novel quaternary ammonium monomers (QAMs) to impart antibacterial activity to dental materials. This review provides a comprehensive overview of the recent advances in quaternary ammonium monomers (QAMs) for dental applications. The current progress and limitations of QAMs are discussed based on the evolution of their structures. The functional diversification and enhancement of QAMs are presented. QAMs have the potential to provide long-term antibacterial activity in dental resin composites, thereby prolonging their service life. However, there is a need to balance antibacterial performance with other material properties and the potential impact on the oral microbiome and general health. Finally, the necessity for further scientific progress in the development of novel quaternary ammonium monomers and the optimization of dental resin formulations is emphasized.

Vip3Aa, secreted by Bacillus thuringiensis, is effective at controlling major agricultural pests such as Spodoptera frugiperda. However, to control Vip3Aa resistance evolved in the field by different lepidoptera species, an in–depth study of sequence––structure––activity relationships is necessary to design new Vip3Aa variants. In this study, the four specific loops (β4–β5 loop, β9–β10 loop, β12–β13 loop, and β14–β15 loop) in domain III were selected and four loop mutants were constructed by replacing all residues in each specific loop with alanine. We obtained soluble proteins for three of the loop mutants, excluding the β9–β10 loop. These loop mutants have been characterized by toxicity bioassays against S. frugiperda, proteolytic processing, and receptor binding. These results indicate that the β4–β5 loop and β14–β15 loop are involved in receptor binding and Vip3Aa toxicity. Based on this, we constructed numerous mutants and obtained three single mutants (Vip3Aa–S366T, Vip3Aa–S366L, and Vip3Aa–R501A) that exhibited significantly increased toxicity of 2.61–fold, 3.39–fold, and 2.51–fold, respectively. Compared to Vip3Aa, the receptor affinity of Vip3Aa–S366T and Vip3Aa–S366L was significantly enhanced. Furthermore, we also analyzed and aligned the three–dimensional structures of the mutants and Vip3Aa. In summary, these results indicate that the loops in domain III have the potential to be targeted to enhance the insecticidal toxicity of the Vip3Aa protein.

Deep-learning- and unmanned aerial vehicle (UAV)-based methods facilitate structural crack detection for tall structures. However, contemporary datasets are generally established using images taken with handheld or vehicle-mounted cameras. Thus, these images might be different from those taken by UAVs in terms of resolution and lighting conditions. Considering the difficulty and complexity of establishing a crack image dataset, making full use of the current datasets can help reduce the shortage of UAV-based crack image datasets. Therefore, the performance evaluation of existing crack image datasets in training deep neural networks (DNNs) for crack detection in UAV images is essential. In this study, four DNNs were trained with different architectures based on a publicly available dataset and tested using a small UAV-based crack image dataset with 648 +pixel-wise annotated images. These DNNs were first tested using the four indices of precision, recall, mIoU, and F1, and image tests were also conducted for intuitive comparison. Moreover, a field experiment was carried out to verify the performance of the trained DNNs in detecting cracks from raw UAV structural images. The results indicate that the existing dataset can be useful to train DNNs for crack detection from UAV images; the TransUNet achieved the best performance in detecting all kinds of structural cracks.

Abstract Background Frailty is a common condition in older adults that is characterized by transitions between frailty states in both directions (progression and reversion) over time. Loneliness has been reported to be associated with the incidence of frailty, but few studies have explored the impact of persistent loneliness over time on frailty. In this study, we aimed to whether and how two different types of loneliness, transient and chronic, were associated with changes in frailty status in older adults. Methods The analytic sample contained 2961 adults aged ≥ 60 years who completed interviews for both the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study. The logistic regression model was used to examine the relationship between transient and chronic loneliness and progression and reversion of frailty. Demographics (age, sex, education level, marital status, urban–rural residence), living alone, chronic conditions, physical function, and depressive symptoms from the 2011 wave were adjusted. Results After four years, 21% of the studied sample reported progression, 20% reported reversion in frailty, 31% reported transient loneliness, and 14% reported chronic loneliness. There was no significant difference in participants who reported transient loneliness (OR = 1.10, 95% CI [0.89,1.37]), or chronic loneliness (OR = 1.14, 95% CI [0.84,1.57]) on the progression of frailty, compared with no report of loneliness. Participants reporting chronic loneliness (OR = 0.68, 95% CI [0.50,0.93]) were less likely to report reversion in their level of frailty compared to participants who did not report loneliness but not transient loneliness (OR = 0.87, 95% CI [0.70,1.08]). Conclusions Roughly the same percentage, a fifth, of older Chinese adults progressed or reversed in frailty status without active intervention. Chronic loneliness was related to a lower probability of reversion in the frail group than in the no loneliness group, but not in the transient loneliness group. More attention should be given to older adults with chronic loneliness.

Abstract To evaluate the clinical predictive value of serum alpha-fetoprotein variants (AFP-L2, AFP-L3) in combination with maternal serum prenatal screening biomarkers in predicting fetal trisomy 21 and trisomy 18. We analyze the data of singleton pregnant women at 15–20+6 weeks of 731,922 gravidas from October 2007 to September 2019. The research objects were separated into the following groups: control (n = 569), trisomy 21 (n = 116), and trisomy 18 (n = 52). The cases were diagnosed by chromosomal karyotypic analysis of amniotic fluid cells. Level of AFP-L2 and AFP-L3 were detected in maternal serum among control women and patients. Receiver operator characteristic analysis, detection rate, false positive rate, false negative rate, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio, comprehensive discriminant improvement, net weight classification improvement, decision curve analysis and Hosmer–lemeshow (H-L) test were used to investigate the predictive value of free β-hCG, AFP, AFP-L2 and AFP-L3 on the risk models of trisomy 21, 18. There was a statistically significant difference in maternal serum AFP-L2 and AFP-L3 multiple of the median (MoM) among the trisomy 21, trisomy 18, and control groups. The AUCs of AFP-L2 and AFP-L3 for the screening trisomy 21 and trisomy 18 fetus were 0.785, 0.758 and 0.775, 0.754. According to ROC, the optimal cut-off values of AFP-L2 and AFP-L3 for predicting trisomy 21 and trisomy 18 fetuses all were 1.09 MoM and 1.30 MoM, respectively. The risk-calculation model constructed by AFP-L2 + AFP-L3 MoM manifested better efficiency than the original single-value truncation method using AFP MoM alone. Compared with different modeling methods, the AUC of trisomy 21 fetuses predicted by AFP-L2 + AFP-L3 + free β-hCG achieved an optimal value (0.938), while the AUC of trisomy 18 fetus predicted by AFP-L2 + free β-hCG was the best (0.991). Compared with AFP, the IDI of AFP-L2 or AFP-L3 alone increased 9.56% and 12.34%; the NRI increased 26.50% and 26.70 in predicting trisomy 21. For trisomy 18, the IDI of AFP-L2 or AFP-L3 alone declined with 8.12% and 1.52%; the NRI declined with 13.84% and 8.54%. In the combined model, the model with best detection rate, false positive rate and positive likelihood ratio was AFP-L2 + AFP-L3 + free β-hCG, followed by AFP-L2 + free β-hCG and AFP-L3 + free β-hCG, and finally AFP + free β-hCG. Maternal serum AFP-L2 and AFP-L3 in the second trimester is a good marker for screening trisomy 21 and trisomy18 with high sensitivity and specificity. The combined screening results are better than the single marker, and the efficiency of AFP-L2 + AFP-L3 + free β-hCG is the best.

The Internet and the Internet of Things (IoT) connect the world inside and outside the network through online and offline communication, which forms the original single network virtual platform. The integration of IoT, virtual reality and artificial intelligence can provide intelligent WebVR interaction for various application fields. However, we need to solve the problems of data lightweight, real-time data transmission based on the IoT, and visualization of scene data on the Web. This paper uses the IoT and virtual reality technology to propose a virtual reality scene modeling method based on the IoT platform, as well as the database dynamic loading management method and device of the virtual reality system, which includes building the database, storing the involved data structures for various scenes and functions in the virtual reality system. The time–space IoT engine is connected with the integrated service sharing center. The IoT platform collects data through the IoT sensor system and provides support for the application platform through the integrated service sharing center. The proposed method can meet the needs of large-scale data acquisition and modeling, shorten the loading time, improve the efficiency, and save the wasted computing resources and memory.

Purpose To analyze the factors affecting the elevation of serum procalcitonin (PCT) in patients with extensive burns, and explore its potential value in evaluating the severity and prognosis. Methods Clinical data of 139 patients with extensive burns admitted to our burn center from January 2014 to December 2019 were retrospectively analyzed. Spearman’s Rank correlation coefficient was used to analyze the factors influencing the elevated PCT levels. The predictive power of PCT for death was evaluated by receiver operating characteristic (ROC) and multiple logistic regression analysis. Results 72 cases exhibited elevated serum PCT concentrations during the shock phase, but none of them had obvious signs of infection. PCT level in the shock phase was positively correlated with burn area, depth, degree of inhalation injury, delay in fluid resuscitation, APACHE II, and SOFA scores. The peak values of PCT during shock and infection phases were significantly higher in the non-survivors than in the survivors. The areas under the ROC curve for predicting death were 0.788 and 0.926, respectively, and 5.4 ng/mL (OR = 5.33) and 8.5 ng/mL (OR = 14.49) were the high-risk thresholds for death prediction. Conclusions Serum PCT level in the shock phase is a potential indicator for evaluating the severity of burns, while the PCT level during the infection period can be used as an early warning indicator for severe systemic infection. High levels of PCT peaks during the shock and infection periods indicate an increased risk of poor prognosis, and targeted treatment is required accordingly.

Abstract Objective Neutrophils and aberrant NETosis have been implicated in the pathogenesis of diverse autoimmune diseases; however, their roles in primary Sjögren’s syndrome (pSS) remain unclear. We aimed to reveal the potential roles of neutrophils and neutrophil extracellular traps (NETs) in pSS. Methods pSS patients were enrolled and NETosis markers were measured in plasma and labial glands using ELISA and immunofluorescence. The gene signatures of neutrophils were assessed by RNA-Seq and RT-PCR. Reactive oxygen species (ROS), mitochondrial ROS (MitoSOX) production, and JC-1 were measured by flow cytometry. Results NETosis markers including cell-free DNA (cf-DNA) and myeloperoxidase (MPO) in plasma and labial glands from pSS patients were significantly higher than healthy controls (HCs) and were associated with disease activity. RNA sequencing and RT-qPCR revealed activated type I IFN signaling pathway and higher expression of genes related to type I interferon in pSS neutrophils. Further stimulating with IFN-α 2a in vitro significantly induced ROS production and JC-1 monomer percentage in pSS neutrophils. Conclusions Our data suggest the involvement of neutrophils and enhanced NETosis in pSS patients. Further mechanism study in vitro revealed that type I IFN activation in pSS neutrophils led to mitochondrial damage and related ROS production which finally result in the generation of NETs.

Abstract CD8+ T cells play a central role in anti-tumor immunity. Naïve CD8+ T cells are active upon tumor antigen stimulation, and then differentiate into functional cells and migrate towards the tumor sites. Activated CD8+ T cells can directly destroy tumor cells by releasing perforin and granzymes and inducing apoptosis mediated by the death ligand/death receptor. They also secrete cytokines to regulate the immune system against tumor cells. Mitochondria are the central hub of metabolism and signaling, required for polarization, and migration of CD8+ T cells. Many studies have demonstrated that mitochondrial dysfunction impairs the anti-tumor activity of CD8+ T cells through various pathways. Mitochondrial energy metabolism maladjustment will cause a cellular energy crisis in CD8+ T cells. Abnormally high levels of mitochondrial reactive oxygen species will damage the integrity and architecture of biofilms of CD8+ T cells. Disordered mitochondrial dynamics will affect the mitochondrial number and localization within cells, further affecting the function of CD8+ T cells. Increased mitochondria-mediated intrinsic apoptosis will decrease the lifespan and quantity of CD8+ T cells. Excessively low mitochondrial membrane potential will cause the release of cytochrome c and apoptosis of CD8+ T cells, while excessively high will exacerbate oxidative stress. Dysregulation of mitochondrial Ca2+ signaling will affect various physiological pathways in CD8+ T cells. To some extent, mitochondrial abnormality in CD8+ T cells contributes to cancer development. So far, targeting mitochondrial energy metabolism, mitochondrial dynamics, mitochondria-mediated cell apoptosis, and other mitochondrial physiological processes to rebuild the anti-tumor function of CD8+ T cells has proved effective in some cancer models. Thus, mitochondria in CD8+ T cells may be a potential and powerful target for cancer treatment in the future.

Non-targeted effect is an important complement to the classical target theory of radiation biology which takes nuclear genomic DNA as the core target. The principle of radiation target theory is to assume that an organism or cell has one or more sensitive points or targets, hit and inactivation of which directly by radiation leads to considerable damage and the death event. Recent findings indicate that not only cell nucleus but also other cellular parts can be considered as possible targets. Mitochondrion is considered as a critical organelle where the non-targeted effect is initiated. A series of recent studies have provided substantial evidence and solid data which profoundly facilitate the understanding of radiation-induced non-targeted effects emitted from mitochondrion in the irradiated cells, such the major apparent performances, signaling pathways and biological significance. Mitochondrial genome is more sensitive to genotoxic than nuclear genome. Ionizing radiation can induce mtDNAs double-strand breaks directly or indirectly via increased mitochondrial ROS. Under stress conditions, mitochondrial DNA (mtDNA) fragments are released into the cytoplasm. The cytosol mtDNAs are sensed by cGAS and AIM2 proteins and they activate the corresponding signaling pathways, generating relevant inflammatory and immune responses. These newly developed mitochondrial DNA-initiating pathways may boost the development of targeted therapies for preventing normal tissue toxicity as well as radio-immunotherapy, an emerging trend for cancer therapies. Here we focus and discuss the mechanisms and biological significance of mtDNA-triggering cGAS/AIM2 signaling pathways of immune response from the aspect of non-targeted effect of radiation.

Objective To identify the potential prognostic biomarkers of the immune-related genes signature for patients with hepatocellular carcinoma (HCC). Methods Original HCC data were downloaded from TCGA, and the immune activity of each sample was calculated by ssGSEA. HCC samples were divided into high and low immune cell infiltration groups by "GSVA" package and "hclust" package. The ESTIMATE algorithm scored the tumor microenvironment in each HCC sample. The "limma" package and Venn diagram identified effective immune-related genes. Univariate Cox, Lasso regression and multivariate Cox regression analyses were used to explore key genes. The "rms" package was used to create nomograms and draw calibration curves. Results Compared with the high immune cell infiltration group, the tumor purity of the samples in the low immune cell infiltration group was higher, the immune score, ESTIMATE score and stromal score were lower. In the high immune cell infiltration group, the immune components were more abundant, and the expression levels of TIGIT, PD-L1, PD-1, LAG3, TIM-3, CTLA4 and HLA family were higher. Multivariate Cox regression analysis showed that four immune-related genes (S100A9, HMOX1, IL18RAP and FCER1G) were used to construct the prognosis model. Compared with other clinical features, the risk score of this prognostic model was recognized as an independent prognostic factor. Conclusion This study identified the immune-related core genes which may be used in targeted therapy and immunotherapy of HCC.

Abstract Background Aging disturbs the skin morphology and function, manifested as thinned epithelium and impaired wound healing. As a major type of skin cells, epidermal stem cells (EpiSCs) are inevitably affected by aging. The effect of age on EpiSCs and wound healing needs to be further explored. Methods Skin RNA-seq data of young (5 months) and old (30 months) CB6F1 mice were obtained from GEO Series GSE35322 with 10 in each age group. Differentially expressed genes were analyzed, and EpiSCs-related pathways were enriched by KEGG. The age-related changes of the screened PI3K/Akt pathway were validated by Western Blot and immunofluorescence of epidermis of SD rats (2, 17, and 23 months, n = 6). The expression of upstream protein EGFR was assessed by immunofluorescence in skin of mice (4, 13, and 23 months, n = 6) and human (respectively, 23, 28, 30 years old in the young group and 69, 73, 78 years old in the old group) skin. Inhibitors of EGFR were used to verify its effects on EpiSCs and wound healing. The small molecule drug Tideglusib was tested for its effects on signaling pathways of EpiSCs and wound healing of aged rats. Western Blot was used for the detection of signaling pathways in in vitro experiments. Cell migration assays were used to assess cell migration ability. Flow cytometry was used to detect changes in cell cycle and apoptosis levels. Sulforhodamine B assay and CCK-8 assay were used to evaluate cell proliferation and viability, respectively. Student’s t test and one-way analysis of variance (ANOVA) followed by the multiple comparisons Bonferroni test were used for statistical analysis. The 0.05 level of confidence was accepted as a significant difference. Results EpiSCs-related PI3K/Akt pathway was enriched by KEGG and verified by decreased phosphorylation of Akt (32.1 ± 13.8%, P

Abstract Background Impairments in upper limb motor function and cognitive ability are major health problems experienced by stroke patients, necessitating the development of novel and effective treatment options in stroke care. The aim of this study is to examine the effects of robot-assisted therapy on improving upper limb and cognitive functions in stroke patients. Methods This will be a single-blinded, 2-arm, parallel design, randomized controlled trial which will include a sample size of 86 acute and subacute stroke patients to be recruited from a single clinical hospital in Shanghai, China. Upon qualifying the study eligibility, participants will be randomly assigned to receive either robot-assisted therapy or conventional therapy with both interventions being conducted over a 6-week period in a clinical rehabilitation setting. In addition to comprehensive rehabilitation, the robot-assisted therapy group will receive a 30-min Armguider robot-assisted therapy intervention 5 days a week. Primary efficacy outcomes will include Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Mini-Mental Status Examination (MMSE). Other secondary outcomes will include Trail Making Test (TMT), Auditory Verbal Learning Test (AVLT), Digit Symbol Substitution Test (DSST), and Rey–Osterrieth Complex Figure Test (ROCFT). All trial outcomes will be assessed at baseline and at 6-week follow-up. Intention-to-treat analyses will be performed to examine changes from baseline in the outcomes. Adverse events will be monitored throughout the trial period. Discussion This will be the first randomized controlled trial aimed at examining the effects of robot-assisted therapy on upper limb and cognitive functions in acute and subacute stroke patients. Findings from the study will contribute to our understanding of using a novel robotic rehabilitation approach to stroke care and rehabilitation. Trial registration Chinese Clinical Trial Registry ChiCTR2100050856 . Registered on 5 September 2021.

Abstract Working memory (WM) deficit in schizophrenia is thought to arise from a widespread neural inefficiency. However, we do not know if this deficit results from the illness-related genetic risk and influence the symptom burden in various domains, especially in patients who have an early onset illness. We used graph theory to examine the topology of the functional connectome in 99 subjects (27 early-onset schizophrenia (EOS), 24 asymptomatic siblings, and 48 healthy subjects) during an n-back task, and calculated their polygenic risk score (PRS) for susceptibility to schizophrenia. Linear regression analysis was used to test associations of the PRS, clinical symptoms, altered connectomic properties, and WM accuracy in EOS. Indices of small-worldness and segregation were elevated in EOS during the WM task compared with the other two groups; these connectomic aberrations correlated with increased PRS and negative symptoms. In patients with higher polygenic risk, WM performance was lower only when both the connectomic aberrations and the burden of negative symptoms were higher. Negative symptoms had a stronger moderating role in this relationship. Our findings suggest that the aberrant connectomic topology is a feature of WM task performance in schizophrenia; this relates to higher polygenic risk score as well as higher burden of negative symptoms. The deleterious effects of polygenic risk on cognition are played out via its effects on the functional connectome, as well as negative symptoms.

The equivalent elastic modulus is a parameter for controlling the deformation behavior of fractured rock masses in the equivalent continuum approach. The confining stress, whose effect on the equivalent elastic modulus is of great importance, is the fundamental stress environment of natural rock masses. This paper employs an analytical approach to obtain the equivalent elastic modulus of fractured rock masses containing random discrete fractures (RDFs) or regular fracture sets (RFSs) while considering the confining stress. The proposed analytical solution considers not only the elastic properties of the intact rocks and fractures, but also the geometrical structure of the fractures and the confining stress. The performance of the analytical solution is verified by comparing it with the results of numerical tests obtained using the three-dimensional distinct element code (3DEC), leading to a reasonably good agreement. The analytical solution quantitatively demonstrates that the equivalent elastic modulus increases substantially with an increase in confining stress, i.e. it is characterized by stress-dependency. Further, a sensitivity analysis of the variables in the analytical solution is conducted using a global sensitivity analysis approach, i.e. the extended Fourier amplitude sensitivity test (EFAST). The variations in the sensitivity indices for different ranges and distribution types of the variables are investigated. The results provide an in-depth understanding of the influence of the variables on the equivalent elastic modulus from different perspectives.

Introduction:Porphyromonas gingivalis and Enterococcus faecalis promote the development of pulpitis and periapical periodontitis. These bacteria are difficult to eliminate from the root canal systems, leading to persistent infection and poor treatment outcomes. We explored the response of human dental pulp stem cells (hDPSCs) to bacterial invasion and the mechanisms underlying the impact of residual bacteria on dental pulp regeneration.Methods: Single-cell sequencing was used to categorize the hDPSCs into clusters based on their response to P. gingivalis and E. faecalis. We depicted a single-cell transcriptome atlas of hDPSCs stimulated by P. gingivalis or E. faecalis.Results: The most differentially expressed genes in the Pg samples were THBS1, COL1A2, CRIM1, and STC1, which are related to matrix formation and mineralization, and HILPDA and PLIN2, which are related to the cellular response to hypoxia. A cell cluster characterized by high expression levels of THBS1 and PTGS2 was increased after P. gingivalis stimulation. Further signaling pathway analysis showed that hDPSCs prevented P. gingivalis infection by regulating the TGF-β/SMAD, NF-κB, and MAPK/ERK signaling pathways. Differentiation potency and pseudotime trajectory analyses showed that hDPSCs infected by P. gingivalis undergo multidirectional differentiation, particularly to the mineralization-related cell lineage. Furthermore, P. gingivalis can create a hypoxia environment to effect cell differentiation. The Ef samples were characterized by the expression of CCL2, which is related to leukocyte chemotaxis, and ACTA2, which is related to actin. There was an increased proportion of a cell cluster that was similar to myofibroblasts and exhibited significant ACTA2 expression. The presence of E. faecalis promoted the differentiation of hDPSCs into fibroblast-like cells, which highlights the role of fibroblast-like cells and myofibroblasts in tissue repair.Discussion: hDPSCs do not maintain their stem cell status in the presence of P. gingivalis and E. faecalis. They differentiate into mineralization-related cells in the presence of P. gingivalis and into fibroblast-like cells in the presence of E. faecalis. We identified the mechanism underlying the infection of hDPSCs by P. gingivalis and E. faecalis. Our results will improve understanding of the pathogenesis of pulpitis and periapical periodontitis. Furthermore, the presence of residual bacteria can have adverse effects on the outcomes of regenerative endodontic treatment.

The extracellular matrix (ECM) is assembled by hundreds of proteins orchestrating tissue patterning and surrounding cell fates via the mechanical–biochemical feedback loop. Aberrant ECM protein production or assembly usually creates pathological niches eliciting lesions that mainly involve fibrogenesis and carcinogenesis. Yet, our current knowledge about the pathophysiological ECM compositions and alterations in healthy or diseased tissues is limited since the methodology for precise insoluble matrisome coverage in the ECM is a “bottleneck.” Our current study proposes an enhanced sodium dodecyl sulfonate (E-SDS) workflow for thorough tissue decellularization and an intact pipeline for the accurate identification and quantification of highly insoluble ECM matrisome proteins. We tested this pipeline in nine mouse organs and highlighted the full landscape of insoluble matrisome proteins in the decellularized ECM (dECM) scaffolds. Typical experimental validations and mass spectrometry (MS) analysis confirmed very little contamination of cellular debris remaining in the dECM scaffolds. Our current study will provide a low-cost, simple, reliable, and effective pipeline for tissue insoluble matrisome analysis in the quest to comprehend ECM discovery proteomic studies.

Depression is the most prevalent psychiatric disorder, which needs deeper mechanism research studies and effective therapy. Zi-Shui-Qing-Gan-Yin (ZSQGY) is a traditional Chinese medicine decoction that has been widely used in China in the treatment of depressive symptoms. The aim of the study was to examine the anti-depressive effects of ZSQGY and the possible mechanism of action in the monosodium glutamate (MSG)-induced depressive model and the corticosterone (CORT)-induced PC12 cell model. Liquid chromatography-mass spectrometry (LC–MS) was performed to determine the major compounds in the water extract of ZSQGY. The depressive behaviors were evaluated by the field swimming test (FST), the sucrose preference test (SPT), and the open field test (OFT). Golgi staining and transmission electron microscopy (TEM) were performed to display the alterations of synaptic ultrastructure. The mitochondrion function and inflammatory factors were also quantified. The changes in peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) expression were evaluated. The results of this study demonstrated that ZSQGY significantly improved depressive behaviors. ZSQGY also reversed the changes in synaptic plasticity, improved mitochondrion function, and reduced the levels of inflammatory factors. The neuroprotective effects were accompanied by the increased expression of PGC-1α. However, the beneficial changes were reversed after the inhibition of PGC-1α. These results indicated that ZSQGY effectively could improve depressive behaviors via the mechanisms that regulate synaptic structural plasticity, improve mitochondrion function, and alleviate neuroinflammation, which could, or partly, attribute to the regulation of PGC-1α.

IntroductionThe growing demand for mental health support has highlighted the importance of conversational agents as human supporters worldwide and in China. These agents could increase availability and reduce the relative costs of mental health support. The provided support can be divided into two main types: cognitive and emotional. Existing work on this topic mainly focuses on constructing agents that adopt Cognitive Behavioral Therapy (CBT) principles. Such agents operate based on pre-defined templates and exercises to provide cognitive support. However, research on emotional support using such agents is limited. In addition, most of the constructed agents operate in English, highlighting the importance of conducting such studies in China. To this end, we introduce Emohaa, a conversational agent that provides cognitive support through CBT-Bot exercises and guided conversations. It also emotionally supports users through ES-Bot, enabling them to vent their emotional problems. In this study, we analyze the effectiveness of Emohaa in reducing symptoms of mental distress.Methods and ResultsFollowing the RCT design, the current study randomly assigned participants into three groups: Emohaa (CBT-Bot), Emohaa (Full), and control. With both Intention-To-Treat (N=247) and PerProtocol (N=134) analyses, the results demonstrated that compared to the control group, participants who used two types of Emohaa experienced considerably more significant improvements in symptoms of mental distress, including depression (F[2,244]=6.26, p=0.002), negative affect (F[2,244]=6.09, p=0.003), and insomnia (F[2,244]=3.69, p=0.026).DiscussionBased on the obtained results and participants’ satisfaction with the platform, we concluded that Emohaa is a practical and effective tool for reducing mental distress.

Here, using viral metagenomic method a novel picornavirus (named UJS-2019picorna, GenBank accession number OP821762) was discovered in fecal and blood samples of experimental rabbits (Oryctolagus cuniculus). The complete genome size of UJS-2019picorna is 7832 bp excluding the poly(A)-tail, with GC content of 44.00% and a nucleotide composition of 28.0% A, 28.0% U, 21.5% G, and 22.5% C. The viral genome has a typical picornavirus organization pattern from the 5′-3′ direction: VPg-5′ UTR-(L)-P1, (VP4–VP2–VP3–VP1)–P2, (2 A-2B–2C)–P3, (3 A-3B–3C-3D)-3′ UTR-poly(A). The P1 region of UJS-2019picorna is related to Erbovirus with amino acid identity of 37.31%, while the P2 and P3 regions are the closest to Bopivirus with amino acid identity of 35.66%–39.53%. According to the Picornaviridae Study Group guidelines, UJS-2019picorna should be presumed to be a new genus belonging to the Picornaviridae family. Epidemiologic study revealed that this novel picornavirus was prevalent in a cohort of experimental rabbits, with prevalence rate of 23.68% (9/38) in feces and 18.4% (7/38) in blood samples. Further work is required to elucidate whether this virus is pathogenic to rabbits and whether it has influence on studies using rabbits as experimental animal.

Introduction: Spermatogenesis is sustained by the homeostasis of self-renewal and differentiation of undifferentiated spermatogonia throughout life, which is regulated by transcriptional and posttranscriptional mechanisms. B cell-specific Moloney murine leukemia virus integration site 1 (BMI1), one of spermatogonial stem cell markers, is a member of Polycomb repressive complex 1 (PRC1) and important to spermatogenesis. However, the mechanistic underpinnings of how BMI1 regulates spermatogonia fate remain elusive.Methods: We knocked down BMI1 by siRNA to investigate the role of BMI1 in undifferentiated spermatogonia. Differentially expressed genes were identified by RNA-seq and used for KEGG pathway analysis. We performed ChIP-seq analysis in wild type and BMI1 knockdown cells to explore the underlying molecular mechanisms exerted by BMI1. BMI1-associated alterations in repressive histone modifications were detected via Western blotting and ChIP-seq. Furthermore, we performed mass spectrometry and Co-immunoprecipitation assays to investigate BMI1 co-factors. Finally, we demonstrated the genomic regions occupied by both BMI1 and its co-factor.Results: BMI1 is required for undifferentiated spermatogonia maintenance by both repressing and activating target genes. BMI1 preserves PI3K-Akt signaling pathway for spermatogonia proliferation. Decrease of BMI1 affects the deposition of repressive histone modifications H2AK119ub1 and H3K27me3. BMI also positively regulates H3K27ac deposited genes which are associated with proliferation. Moreover, we demonstrate that BMI1 interacts with Sal-like 4 (SALL4), the transcription factor critical for spermatogonia function, to co-regulate gene expression.Discussion: Overall, our study reveals that BMI1 safeguards undifferentiated spermatogonia fate through multi-functional roles in regulating gene expression programs of undifferentiated spermatogonia.

The “developmental origins of health and disease” (DOHaD) hypothesis posits that early-life environmental exposures have a lasting impact on individual’s health and permanently shape growth, structure, and metabolism. This reprogramming, which results from fetal stress, is believed to contribute to the development of adulthood cardiovascular diseases such as hypertension, coronary artery disease, heart failure, and increased susceptibility to ischemic injuries. Recent studies have shown that prenatal exposure to drugs, such as glucocorticoids, antibiotics, antidepressants, antiepileptics, and other toxins, increases the risk of adult-onset cardiovascular diseases. In addition, observational and animal experimental studies have demonstrated the association between prenatal drug exposure and the programming of cardiovascular disease in the offspring. The molecular mechanisms underlying these effects are still being explored but are thought to involve metabolism dysregulation. This review summarizes the current evidence on the relationship between prenatal drug exposure and the risk of adult cardiovascular disorders. Additionally, we present the latest insights into the molecular mechanisms that lead to programmed cardiovascular phenotypes after prenatal drug exposure.

Abstract Sodium metal, with a high theoretical specific capacity of 1165 mAh g−1, is the ultimate anode for sodium batteries, yet how to deal with the inhomogeneous and dendritic sodium deposition and the infinite relative dimension change of sodium metal anodes during sodium depositing/stripping is still challenging. Here, a facile fabricated sodiuphilic 2D N‐doped carbon nanosheets (N‐CSs) are proposed as sodium host material for sodium metal batteries (SMBs) to prevent dendrite formation and eliminate volume change during cycling. Revealing from combined in situ characterization analyses and theoretical simulations, the high nitrogen content and porous nanoscale interlayer gaps of the 2D N‐CSs can not only concede dendrite‐free sodium stripping/depositing but also accommodate the infinite relative dimension change. Furthermore, N‐CSs can be easily process into N‐CSs/Cu electrode via traditional commercial battery electrode coating equipment that pave the way for large‐scale industrial applications. On account of the abundant nucleation sites and sufficient deposition space, N‐CSs/Cu electrodes demonstrate a superior cycle stability of more than 1500 h at a current density of 2 mA cm−2 with a high coulomb efficiency of more than 99.9% and ultralow nucleation overpotential, which enable reversible and dendrites‐free SMBs and shed light on further development of SMBs with even higher performance.

Summary: Kimura’s disease is a rare chronic inflammatory disorder characterized with subcutaneous masses, lymphadenopathy, and peripheral eosinophilia. So far, the disease pathogenesis remains hardly known. Here, we perform bulk-RNA sequencing and reveal a higher expression of transmembrane 176A (TMEM176A) with over-activated extracellular-signal-regulate kinase/mitogen-activated protein kinases (Erk/MAPK) signaling pathway in eosinophils of Kimura’s disease compared with healthy controls. Flow cytometry analysis shows that the composition of lymphocytes, monocytes, and dendritic cell subsets are similar between Kimura’s disease and healthy controls, which is further validated by scRNA-seq. Loss of S100 calcium binding protein P (S100P) is found in the CD24+ myeloid subset of Kimura’s disease. In vitro functional assays show that S100P may participate in promoting reactive oxygen species (ROS) production in myeloid cells. Taken together, we are the first to study the immune pathogenesis systematically and demonstrate that Erk/MAPK signaling pathway might be a potential therapeutic target for Kimura’s disease.

Large-scale and dynamic surface water mapping is crucial for understanding the impact of global climate change and human activities on the distribution of surface water resources. Remote sensing imagery has become the primary data source for surface water mapping due to its high spatiotemporal resolution and wide coverage. However, the reliability of current water products during flood seasons is limited due to the influence of clouds on optical remote sensing images. Moreover, annual and seasonal surface water mapping cannot capture intra-month variations of water bodies. To address these challenges, we proposed a high spatiotemporal surface water mapping framework on Google Earth Engine that combines multi-source remote sensing data. Our framework can generate 10 m spatial resolution surface water maps at a 15-day time step. We classified water bodies using Sentinel-2 images and a classification tree algorithm, and then used Sentinel-1 data to compensate for cloudy and missing data areas in Sentinel-2 images, resulting in seamless cloud-unaffected surface water maps. We evaluated the effectiveness of our proposed framework in six floodplains around the world, and experimental results demonstrate that the water maps generated by our framework outperform existing public datasets and our framework has great potential for hydrological applications. Our proposed framework can capture the details of surface water dynamics with higher spatial and temporal resolution and is free from cloud influence, which is necessary for water resources management, flood monitoring, and disaster response.

IntroductionDorsal root ganglia (DRG) are anatomically well-defined structures that contain all primary sensory neurons and are distension nodules of the dorsal root in the spinal cord near the medial surface of each foramen. Therefore, DRG is considered to be a desirable target for injection to manage chronic pain. But it presents a limitation in probing deep into it without in vivo injection technology.MethodsHere, we described a technique for administering intraganglionic injections of lumbar DRG under direct vision. We use partial osteotomy rather than laminectomy, which removes more bone, to preserve spinal structures while gaining adequate DRG access. To monitor the intraoperative progress of the DRG injection, a non-toxic dye was utilized. The effectiveness of the injection on the diffusion of AAV (adeno-associated virus) within the ganglion was assessed by histopathology at postoperative day 21.ResultsBehavioral tests showed that neither motor nor sensory abilities were affected by saline or AAV injections. Meanwhile, the decreased pain threshold of SNI (spared nerve injury) was considerably restored by pharmacological inhibition of DRG neurons.DiscussionOur research achieved a new minimally invasive and intuitive intra-ganglionic injection in mice. In addition, the present protocol may serve as a valuable resource for planning preclinical studies of DRG injection.

Objectives To investigate the effectiveness and safety of TCZ (tocilizumab) monotherapy for chronic periaortitis (CP) patients at acute active stage.Methods Twelve patients with definite or possible diagnosis of CP were enrolled and received intravenous infusions of TCZ (8 mg/kg) every 4 weeks for at least 3 months. Clinical features, laboratory and imaging findings were recorded at baseline and during the follow-up. The primary endpoint was the rate of partial and complete remission after 3 months TCZ monotherapy and the secondary endpoint was the frequency of treatment related adverse events.Results Three patients (27.3%) achieved partial remission and seven patients (63.6%) obtained complete remission after 3 months TCZ treatment. The total remission rate achieved 90.9%. All patients reported improvement in clinical symptoms. Inflammatory markers such as erythrocyte sedimentation rate and C reactive protein decreased to normal levels after TCZ treatment. Nine patients (81.8%) showed remarkable shrinkage of perivascular mass greater than or equal to 50% on CT.Conclusion Our study showed that TCZ monotherapy contributed to remarkable clinical and laboratory improvement in CP patients and could be an alternative treatment option for CP.

Objective: Wiedemann-Steiner syndrome (WSS) is a rare autosomal dominant disorder caused by deleterious heterozygous variants of the KMT2A gene. This study aims to describe the phenotypic and genotypic features of Chinese WSS patients, and assess therapeutic effects of recombinant human growth hormone (rhGH).Methods: Eleven Chinese children with WSS were enrolled in our cohort. Their clinical, imaging, biochemical and molecular findings were analyzed retrospectively. Moreover, the phenotypic features of 41 previously reported Chinese WSS patients were reviewed and included in our analysis.Results: In our cohort, the 11 WSS patients presented with classic clinical manifestations, but with different frequencies. The most common clinical features were short stature (90.9%) and developmental delay (90.9%), followed by intellectual disability (72.7%). The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain. In the set comprising 52 Chinese WSS patients, the most common clinical and imaging manifestations were developmental delay (84.6%), intellectual disability (84.6%), short stature (80.8%) and delayed bone age (68.0%), respectively. Eleven different variants, including three known and eight novel variants, of the KMT2A gene were identified in our 11 WSS patients without a hotspot variant. Two patients were treated with rhGH and yielded satisfactory height gains, but one developed acceleration of bone age.Conclusion: Our study adds 11 new patients with WSS, reveals different clinical characteristics in Chinese WSS patients, and extends the mutational spectrum of the KMT2A gene. Our study also shares the therapeutic effects of rhGH in two WSS patients without GH deficiency.

Background: 17α-hydroxylase deficiency (17OHD) is an autosomal recessive genetic disease characterized by low renin hypertension, abnormal sexual development, and reduced androgen levels. The morbidity rate of 17OHD is less than 1/10,000, and a lack of knowledge of this condition may lead to misdiagnosis and delayed treatment. Case presentation: This is a case report of a patient suffering from hypertension who was diagnosed with 17OHD. The patient was misdiagnosed for more than 20 years. The patient presented with hypertension, hypokalemia, sexual infantilism, and delayed bone age. The patient had a 46, XY karyotype and a homozygous mutation of the CYP17A1 gene. The mutation site was c.1319G > A (p.Arg440His). After she took Nifedipine Sustained Release Tablets 30 mg once a day in the morning, her blood pressure dropped and is currently under control at about 145/95 mmHg. Conclusions: With clinicians’ increasing awareness of 17OHD, effective treatment based on early diagnosis should correct hypogonadism and avoid the cardiovascular and cerebrovascular complications of hypertension.

Introduction: Bioremediation has been shown to be an effective strategy for removing toxic pollutants from the environment, particularly organic chemicals such as petroleum hydrocarbons. This paper investigates the changes in toxicity of petroleum-contaminated soil as a result of microbial remediation processes.Methods: Changes in the ecotoxicity of the contaminated soil were examined using a plant, earthworm, enzyme activity and luminescent bacteria toxicity tests.Results: The results showed that bioremediation could effectively degrade petroleum hydrocarbon (C10–C40) pollutants. After 42 days of remediation, the petroleum hydrocarbon (C10–C40) content of Group A (bioaugmented polluted wetland soil) decreased from 1.66 g/kg to 1.00 g/kg, and the degradation rate was 40.6%. The petroleum hydrocarbon (C10–C40) content of Group B (bioaugmented polluted farmland soil decreased from 4.00 g/kg to 1.94 g/kg, and the degradation rate was 51.6%. During the microbial remediation progress, the ecological toxicity of petroleum-contaminated soil first increased and then decreased. The photosynthetic pigment content index in the higher plant toxicity test, the earthworm survival index and the soil catalase activity all showed good agreement with the relative luminescence index of extracted DCM/DMSO in the luminescent bacterial toxicity test. The soil toxicity decreased significantly after remediation. Specifically, the photosynthetic pigment content of wheat were inhibited in the soil during the whole process (remediation for 42 days), and decreased to the minimum on remediation day 21. The 7-day and 14-day survival rate of earthworms in Group A and Group B gradually decreased in the soil remediation process, and then gradually increased, survival rate at the end of remediation was higher than at the beginning. Soil catalase activity was significantly negatively correlated with petroleum hydrocarbon (C10–C40) content (−0.988, −0.989). The ecological toxicity of contaminated soil reached to the maximum on the 21st day of remediation, relative luminosity of luminescent bacteria in dichloromethane/dimethyl sulfoxide extracts from Group A and Group B were 26.3% and 16.3%, respectively.Conclusion: Bioremediation could effectively degrade petroleum hydrocarbon (C10–C40) pollutants. Wheat photosynthetic pigment content, earthworm survival rate, soil catalase activity and relative luminescence of luminescent bacteria can better indicate the ecological toxicity of petroleum-contaminated soil in bioremediation process.

Oxidative stress was one of the major causes of heavy metal-induced toxicity in organisms. The polysaccharide from Bletilla striata (Orchidaceae) (BSP) has been recently recognized as a novel player in the management of oxidative stress response in organisms. Here, we took the midgut of adult Drosophila melanogaster (Diptera: Drosophilidae) (D. melanogaster), a functional equivalent to the mammalian intestine and stomach, as a model to evaluate the protective effects of BSP (50 μg/mL) on mercuric chloride-induced gastrointestinal toxicology in insects. As a result, BSP exposure significantly improved the survival rates and climbing ability of adult flies exposed to mercury. Further study demonstrated that BSP significantly alleviated the mercury-induced oxidative injury to midgut epithelium, at least partly, through increasing antioxidant enzyme activity (glutathione-S-transferase and superoxide dismutase), decreasing reactive oxidative species production, inhibiting cell death, restoring intestinal epithelial barrier and regulating intestinal stem cell-mediated tissue regeneration. Additionally, sestrin, an oxidative-stress gene, was required in mediating the protection of BSP against mercury-induced oxidative damage to midgut. This study suggested that BSP has great potential for future application in the treatment and prevention of heavy metal-induced gastrointestinal adversities in mammals.

Background: Cerebral ischemia is one of the leading causes of neurological deficit, dementia, and disability globally. Salvianolic acids for injection (SAFI), a multi-component drug derived from Salvia miltiorrhiza L., has been clinically used in China to treat ischemic stroke. Purpose: This study was designed to investigate the mechanisms of SAFI in alleviating cerebral ischemia-induced neurodegeneration, especially its regulatory effects on excessive ER stress. Basic procedures: The rat acute cerebral ischemic injury model was established by a 1.5 h occlusion of the middle cerebral artery followed by 24 h of reperfusion. The neurological deficits, neurobehavior, cerebral infarct volume and edema of rats were examined. Hematoxylin and eosin staining, transmission electron microscopy analysis and TUNEL staining were performed to study the brain injury and cell apoptosis. Western blot and immunofluorescence assay were carried out to study the effects and mechanism of SAFI on ischemic injury. Main findings: Results showed that SAFI significantly inhibited the acute neurodegeneration, reduced brain infarct volumes and decreased brain water content of rats. SAFI also downregulated the relative protein levels of Bax/Bcl-2, Bim, Caspase-12, and reduced the number of TUNEL-positive cells in brain tissue, indicating the anti-apoptotic effects of SAFI. Both of immunofluorescence assay and western blot results showed that SAFI downregulated the expression of endoplasmic reticulum (ER) stress maker GRP78. SAFI dramatically inhibited the ER stress-related PERK/eIF2α/ATF4/CHOP and IRE1α/TRAF2/ASK1/JNK signaling pathways. SAFI also alleviated NF-κB triggered inflammatory response, and inhibited the production of IL-6 and IL-β. Conclusions: Our studies indicated that inhibition of excessive ER stress contributes to the protective effects of SAFI against cerebral ischemia-induced neurodegeneration and neuroinflammation.

In this study, we investigated the feasibility of Ginkgo biloba seeds powder by solid-state fermentation with Eurotium cristatum for developing high-value ginkgo seeds products. The optimum fermentation medium was consisted of 10 g of 40-mesh ginkgo seeds powder loaded in 100 mL Erlenmeyer flask with 50% (w/w) of water content, 4% (w/w) of MgSO4 and 5% (w/w) of KH2PO4 addition. The optimum fermentation conditions were pH 5.0, 2 × 108 CFU/g of inoculum size, 3 mL of sterilized water supplemented every two days during the four days of fermentation. Through fermentation, the spore number of E. cristatum was improved by about 36 times with the production of lovastatin reaching (54.10±0.16) µg/g. The antioxidant activity of fermented ginkgo seeds powder also got obvious enhancement, which could help eliminate excess free radicals produced by normal metabolism. The content of free amino acids increased by 82.32%. Except that the sugar was consumed in some degree, the other nutritional and functional components were well preserved while the content of detrimental ginkgolic acids was reduced by 44.97%. In addition, fermented ginkgo seeds powder possessed better digestibility and showed pleasant orange-like smelling. In conclusion, the quality of ginkgo seeds powder was remarkably improved through solid-state fermentation by using E. cristatum, which could be a promising way for functional applications of ginkgo seeds.

Abstract Background Osteoporotic vertebral fractures are often clinically silent and unrecognized. The present study aimed to determine whether routine chest radiographs could be a potential screening tool for identifying missed vertebral fractures in men aged over 50 years or postmenopausal women, especially those with type 2 diabetes mellitus (T2DM). In this study, we aimed to determine the prevalence of undetected vertebral fractures in elderly Chinese patients with and without T2DM. Methods Clinical data and chest radiographs of 567 individuals with T2DM (T2DM group) and 583 without diabetes (nondiabetic group) at a tertiary hospital in central south China were extracted from the records. Vertebral fractures were specifically looked for on chest radiographs and classified using the Genant semi-quantitative scale. Prevalence was compared between the two groups. Results Mean age and sex composition were comparable between the two groups. Mean weight and body mass index were significantly lower in the T2DM group. In both groups, fractures mostly involved the T11–12 and L1 vertebrae. Moderate/severe fractures were identified in 33.3% individuals in the T2DM group (31.4% men and 36.0% women) versus 23.2% individuals (20.9% men and 25.5% women) in the nondiabetic group. Conclusions Routine chest radiographs could be a useful screening tool for identifying asymptomatic vertebral fractures. Trial registration The study was designed as an observational retrospective study, therefore a trial registration was not necessary.