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Overwintering is a critical part of the annual cycle for species that live in temperate, polar, and alpine regions. Consequently, low-temperature biology is a key determinant of temperate species distribution. Termites are distributed predominantly in tropical regions, and a limited number of species are found in the temperate zone. Here, in the termite Reticulitermes speratus, we report the discovery of an underground chamber that protects kings and queens to survive the winter, which is separate from the one they used during the warmer breeding season. In the spring, the royals inhabited decayed logs on the ground, then moved to their underground chamber located in the roots of stumps in the fall. The winter minimum temperature measured in the royal chamber was higher than that in the logs on the ground. In overwintering termites, the kings and queens had higher cold tolerance than workers and soldiers. Air temperatures dropped below the critical temperature multiple times, as evidenced from the past 140 years of weather records in Kyoto. These results demonstrated the survival strategies of reproductives to overcome the environment at the latitudinal limits. This study helps further the understanding of the termite’s seasonal phenology, long-term survivorship, and life cycle.

Background Atopic dermatitis (AD) is an inflammatory skin condition distinguished by an activated Th2 immune response. The local skin microbial dysbiosis is a contributing factor to the development of AD. The pathogenic coagulase-positive Staphylococcus aureus is the primary species responsible for the progression of AD. Even though Staphylococcus pseudintermedius is an animal-origin pathogen, it is increasingly becoming a source of concern in human diseases. As another coagulase-positive Staphylococci, it is crucial to pay more attention to S. pseudintermedius isolated from the lesion site. Results In our investigation, we presented a case of cheilitis in a patient with atopic dermatitis (AD). We utilized culture and next-generation genomic sequencing (NGS) to identify the bacteria present on the skin swabs taken from the lip sites both prior to and following treatment. Our findings indicated that the predominant bacteria colonizing the lesion site of AD were S. pseudintermedius and S. aureus, both of which were eradicated after treatment. The Multi-locus sequence typing (MLST) of S. pseudintermedius and S. aureus demonstrated coordinated antibiotic susceptibility, with ST2384 and ST22 being the respective types. Although the skin abscess area resulting from S. pseudintermedius infection was significantly smaller than that caused by S. aureus in mice, the expression of cytokines interleukin-4 (IL-4) and interleukin-5 (IL-5) were significantly higher in the S. pseudintermedius-infected mice. Conclusions The S. pseudintermedius strain isolated from the lesion site of the AD patient exhibited a higher expression of IL-4 and IL-5 when colonized on mouse skin, as compared to S. aureus. This observation confirms that S. pseudintermedius can effectively induce the Th2 response in vivo. Our findings suggest that animal-origin S. pseudintermedius may play a role in the development of AD when colonized on the skin, emphasizing the importance of taking preventive measures when in contact with animals.

Epigenetic memory is essential for life that governs the predefined functional features of cells. Recent evidence has indicated that the epigenetic modification provides a potential link to gene expression changes that may be involved in the development of various chronic diseases, and targeting the epigenome becomes a plausible method for treating diseases. Traditional herbal medicine has gradually entered the vision of researchers due to its low toxicity and its effectiveness in treating diseases. As a matter of fact, researchers found that the possessed epigenetic modification capacity of herbal medicine had the ability to combat the progression of the disease, such as various types of cancer, diabetes, inflammation, amnesia, liver fibrosis, asthma, and hypertension-induced renal injury. Studies on the epigenetic effects of herbal medicine will provide valuable insights into the molecular mechanisms of human diseases, which may lead to new therapeutic approaches and diagnoses. Thus, this review summarized the impact of herbal medicine and its bioactive components on disease epigenome as examples of how utilization of epigenetic plasticity could be useful as the basis for the future development of targeted therapies in chronic diseases.

We propose a robust fuzzy design model for a sustainable closed-loop supply chain network. The model is based on a risk dynamic regulation mechanism. In this way, we can solve the problem of sudden disruptions and uncertain demand in the supply chain of Chinese herbal medicines. We also develop a hybrid algorithm solution to solve the model and design a resilient supply chain network. The specific steps are as follows: (1) The risk dynamic regulation mechanism is created with strong risk resistance by considering the information sharing platform, facility defense, drying station scheduling, safety stock, and shared inventory. (2) Based on the dynamic risk regulation mechanism, we establish a sustainable Chinese herbal medicine supply chain network design model. Then, we use the robust fuzzy method and the epsilon constraint to deal with the uncertainty and integrate the model. (3) We introduce opposition-based learning, cosine convergence factor, and levy flight to the original Whale and Grey wolf algorithms to obtain the Hybrid algorithm, which is used to solve the processed model. The results show the model and algorithm proposed in this paper have strong applicability and advantages in designing closed-loop supply chain networks for Chinese herbal medicine and provide references for relevant decision-makers.

Background Temperature variability (TV) is associated with increased mortality risks. However, the independent impacts of interday and intraday are still unknown. Methods We proposed a new method to decompose TV into interday TV and intraday TV through algebra derivation. Intraday TV was defined as the weighted average standard deviation (SD) of minimum temperature and maximum temperature on each day. Interday TV was defined as the weighted SD of daily mean temperatures during the exposure period. We then performed an illustrative analysis using data on daily mortality and temperature in France in 2019–2021. Results The novel interday and intraday TV indices were good proxies for existing indicators, inlcluding diurnal temperature range (DTR) and temperature change between neighbouring days (TCN). In the illustrative analyses, interday and intraday TVs showed differentiated mortality risks. Mortality burden related to TV was mainly explained by the intraday component, accounting for an attributable fraction (AF) of 1.81% (95% CI: 0.64%, 2.97%) of total mortality, more than twice the AF of interday TV (0.86%, 95% CI: 0.47%, 1.24%). Conclusions This study proposed a novel method for identifying and isolating the different components of temperature variability and offered a comprehensive way to investigate their health impacts.

Background Non-pharmaceutical interventions (NPIs) have been implemented worldwide to suppress the spread of coronavirus disease 2019 (COVID-19). However, few studies have evaluated the effect of NPIs on other infectious diseases and none has assessed the avoided disease burden associated with NPIs. We aimed to assess the effect of NPIs on the incidence of infectious diseases during the COVID-19 pandemic in 2020 and evaluate the health economic benefits related to the reduction in the incidence of infectious diseases. Methods Data on 10 notifiable infectious diseases across China during 2010–2020 were extracted from the China Information System for Disease Control and Prevention. A two-stage controlled interrupted time-series design with a quasi-Poisson regression model was used to examine the impact of NPIs on the incidence of infectious diseases. The analysis was first performed at the provincial-level administrative divisions (PLADs) level in China, then the PLAD-specific estimates were pooled using a random-effect meta-analysis. Results A total of 61,393,737 cases of 10 infectious diseases were identified. The implementation of NPIs was associated with 5.13 million (95% confidence interval [CI] 3.45‒7.42) avoided cases and USD 1.77 billion (95% CI 1.18‒2.57) avoided hospital expenditures in 2020. There were 4.52 million (95% CI 3.00‒6.63) avoided cases for children and adolescents, corresponding to 88.2% of total avoided cases. The top leading cause of avoided burden attributable to NPIs was influenza [avoided percentage (AP): 89.3%; 95% CI 84.5‒92.6]. Socioeconomic status and population density were effect modifiers. Conclusions NPIs for COVID-19 could effectively control the prevalence of infectious diseases, with patterns of risk varying by socioeconomic status. These findings have important implications for informing targeted strategies to prevent infectious diseases.

Background Diabetes mellitus (DM) is a prevalent non-communicable metabolic disease, and S100A11 is a newly identified gene closely related to metabolism. The association of S100A11 with diabetes is unclear. This study aimed to assess the relationship between S100A11 and markers of glucose metabolism in patients with different glucose tolerance and gender. Methods This study included 97 participants. Baseline data were obtained, and the serum levels of S100A11 and metabolic markers (glycated hemoglobin [HbA1c], insulin release test, and oral glucose tolerance test) were measured. Linear and nonlinear correlations between serum S100A11 levels and HOMA-IR, HOMA of β, HbA1c, insulin sensitivity index (ISI), corrected insulin response (CIR), and oral disposition index (DIo) were analyzed. The expression of S100A11 was also detected in mice. Results Serum S100A11 levels increased in patients with impaired glucose tolerance (IGT) of both genders. S100A11 mRNA and protein expression increased in obese mice. There were nonlinear correlations between S10011 levels and CIR, FPI, HOMA-IR, whole-body ISI in the IGT group. S100A11 was nonlinearly correlated with HOMA-IR, hepatic ISI, FPG, FPI, and HbA1c in the DM group. In the male group, S100A11 was linearly correlated with HOMA-IR and nonlinearly correlated with DIo (derived from hepatic ISI) and HbA1c. In the female population, S100A11 was nonlinearly correlated with CIR. Conclusions Serum S100A11 levels were highly expressed in patients with IGT and in the liver of obese mice. In addition, there were linear and nonlinear correlations between S100A11 and markers of glucose metabolism, demonstrating that S100A11 has a role in diabetes. Trial registration ChiCTR1900026990

Clinical studies have shown that osteoprotegerin (OPG) is reduced in patients with nonalcoholic steatohepatitis (NASH), but the underlying mechanisms are unclear. The current study focuses on the role of OPG in the NASH pathogenesis. OPG knockout mice and wild-type control mice fed a methionine choline-deficient diet (MCD) for 4 weeks resulted in an animal model of NASH. Measurement of triglycerides (TG) in serum and liver to assess steatosis. Hematoxylin eosin (HE), Sirius Red and Masson staining were used to assess the liver damage. Transcriptome sequencing analysis, qPCR and western blot were to analyze changes in lipid metabolism and inflammation-related indicators in the liver. In vivo knockout of OPG resulted in a reduction of TG levels in the liver and a significant increase in serum ALT and AST. The expression of inflammatory factors and fibrosis genes was significantly upregulated in the livers of OPG knockout mice. Transcriptome sequencing analysis showed that OPG knockout significantly enhanced MCD diet-induced activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Mechanistically, OPG may inhibit MAPK signaling pathway activity by upregulating the expression of dual specificity phosphatase 14 (DUSP14), thereby reducing inflammatory injury. OPG could regulate the activity of the MAPK signaling pathway via DUSP14, thus regulating the expression of some inflammatory factors in NASH, it may be a promising target for the treatment of NASH.

Background In the context of climate change, it has been well observed that short-term temperature variability (TV) could increase the overall and cause-specific mortality and morbidity. However, the association between long-term TV and a broader spectrum of diseases is not yet well understood, especially in the elderly. Methods Our study used data from the fourth Urban and Rural Elderly Population (UREP) study. Long-term TV was calculated from the standard deviation (SD) of daily minimum and maximum temperatures within the study periods (2010–2014, 2011–2014, 2012–2014, 2013–2014, and 2014). Ten self-reported diseases and conditions were collected by questionnaire, including cataract, hypertension, diabetes, cardio-cerebrovascular diseases, stomach diseases, arthritis, chronic lung disease, asthma, cancer, and reproductive diseases. The province-stratified logistic regression model was used to quantify the association between long-term TV and the prevalence of each disease. Results A total of 184,047 participants were included in our study. In general, there were significant associations between TV and the prevalence of most diseases at the national level. Cardio-cerebrovascular disease (OR: 1.16, 95% CI: 1.13, 1.20) generated the highest estimates, followed by stomach diseases (OR: 1.15, 95% CI: 1.10, 1.19), asthma (OR: 1.14, 95% CI: 1.06, 1.22), chronic lung diseases (OR: 1.08, 95% CI: 1.03, 1.13), arthritis (OR: 1.08, 95% CI: 1.05, 1.11), and cataract (OR: 1.06, 95% CI: 1.02, 1.10). Moreover, the associations varied by geographical regions and across subgroups stratified by sex, household income, physical activity, and education. Conclusions Our study showed that long-term exposure to TV was associated with the prevalence of main diseases in the elderly. More attention should be paid to the elderly and targeted strategies should be implemented, such as an early warning system.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sestrin2 (SESN2), a highly evolutionarily conserved protein, is critically involved in the cellular response to various stresses and has been confirmed to maintain the homeostasis of the internal environment. However, the potential effects of SESN2 in regulating dendritic cells (DCs) pyroptosis in the context of sepsis and the related mechanisms are poorly characterized. In this study, we found that SESN2 was capable of decreasing gasdermin D (GSDMD)-dependent pyroptosis of splenic DCs by inhibiting endoplasmic reticulum (ER) stress (ERS)-related nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated ASC pyroptosome formation and caspase-1 (CASP-1) activation. Furthermore, SESN2 deficiency induced NLRP3/ASC/CASP-1-dependent pyroptosis and the production of proinflammatory cytokines by exacerbating the PERK–ATF4–CHOP signaling pathway, resulting in an increase in the mortality of septic mice, which was reversed by inhibiting ERS. These findings suggest that SESN2 appears to be essential for inhibiting NLRP3 inflammasome hyperactivation, reducing CASP-1-dependent pyroptosis, and improving sepsis outcomes through stabilization of the ER. The present study might have important implications for exploration of novel potential therapeutic targets for the treatment of sepsis complications. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-021-03970-z.

Sirt6, a class III NAD+-dependent deacetylase of the sirtuin family, is a highly specific H3 deacetylase and plays important roles in regulating cellular growth and death. The induction of oxidative stress and death is the critical mechanism involved in cardiomyocyte injury and cardiac dysfunction in doxorubicin-induced cardiotoxicity, but the regulatory role of Sirt6 in the fate of DOX-impaired cardiomyocytes is poorly understood. In the present study, we exposed Sirt6 heterozygous (Sirt6+/−) mice and their littermates as well as cultured neonatal rat cardiomyocytes to DOX, then investigated the role of Sirt6 in mitigating oxidative stress and cardiac injury in the DOX-treated myocardium. Sirt6 partial knockout or silencing worsened cardiac damage, remodeling, and oxidative stress injury in mice or cultured cardiomyocytes with DOX challenge. Cardiomyocytes infected with adenoviral constructs encoding Sirt6 showed reversal of this DOX-induced damage. Intriguingly, Sirt6 reduced oxidative stress injury by upregulating endogenous antioxidant levels, interacted with oxidative stress-stirred p53, and acted as a co-repressor of p53 in nuclei. Sirt6 was recruited by p53 to the promoter regions of the target genes Fas and FasL and further suppressed p53 transcription activity by reducing histone acetylation. Sirt6 inhibited Fas/FasL signaling and attenuated both Fas-FADD-caspase-8 apoptotic and Fas-RIP3 necrotic pathways. These results indicate that Sirt6 protects the heart against DOX-induced cardiotoxicity by upregulating endogenous antioxidants, as well as suppressing oxidative stress and cell death signaling pathways dependent on ROS-stirred p53 transcriptional activation, thus reducing Fas–FasL-mediated apoptosis and necrosis.

This paper focuses on the mechanism of rock cutting with conical picks under different confining pressures. First, the 2-dimensional numerical model of rock cutting with two conical picks is established by particle flow code software. Then, the basic contents of cutting modes, cutting efficiency, optimal cutting space, rock fragmental size and crack growth ability are studied. Finally, the cutting modes are verified by cutting experiments. According to the results, the confining pressure directly affects the crack growth ability, it presents four basic cutting modes for different crack growth abilities, mode a, mode b, mode c and mode d, respectively. And they influence the cutting efficiency, optimal cutting space, cutting force and crack growth ability. At no confining pressure, the optimal cutting space is 70 mm, the optimal cutting space is 90 mm under 5 MPa and 10 MPa conditions. The research can provide some reference and guidance for continuous miner construction in different confining pressure environments.

Nowadays, obesity is one of the largest public health problems worldwide. In the last few decades, there has been a marked increase in the obesity epidemic and its related comorbidities. Worldwide, more than 2.2 billion people (33%) are affected by overweight or obesity (712 million, 10%) and its associated metabolic complications. Although a high heritability of obesity has been estimated, the genetic variants conducted from genetic association studies only partially explain the variation of body mass index. This has led to a growing interest in understanding the potential role of epigenetics as a key regulator of gene-environment interactions on the development of obesity and its associated complications. Rapid advances in epigenetic research methods and reduced costs of epigenome-wide association studies have led to a great expansion of population-based studies. The field of epigenetics and metabolic diseases such as obesity has advanced rapidly in a short period of time. The main epigenetic mechanisms include DNA methylation, histone modifications, microRNA (miRNA)-mediated regulation and so on. DNA methylation is the most investigated epigenetic mechanism. Preliminary evidence from animal and human studies supports the effect of epigenetics on obesity. Studies of epigenome-wide association studies and genome-wide histone modifications from different biological specimens such as blood samples (newborn, children, adolescent, youth, woman, man, twin, race, and meta-analysis), adipose tissues, skeletal muscle cells, placenta, and saliva have reported the differential expression status of multiple genes before and after obesity interventions and have identified multiple candidate genes and biological markers. These findings may improve the understanding of the complex etiology of obesity and its related comorbidities, and help to predict an individual’s risk of obesity at a young age and open possibilities for introducing targeted prevention and treatment strategies.

Background The M-type phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN) is a common immune-related disease in adults. Vascular endothelial growth factor A (VEGFA) is the key mediator of angiogenesis, which leads to numerous kidney diseases. However, the role of VEGFA in IMN is poorly understood. Methods In the present study, we downloaded the microarray data GSE115857 from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified with R software. The cytoHubba plug-in were used to identify hub genes from the protein–protein interaction network. Gene set enrichment analysis (GSEA) was used to identify signalling pathway in IMN. CCK8 was performed to assess the cell viability in human vascular endothelial cells (HVECs). Then, passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A antiserum. Animals treated with VEGFA inhibitor bevacizumab (BV), with saline as a positive control. Proteinuria was evaluated by biochemical measurements. Immunohistochemistry and immunofluorescence was used to evaluate relative proteins expression. Electron microscopy was performed to observe the thickness of the glomerular basement membrane (GBM). Results We revealed 3 hub genes, including one up-regulated gene VEGFA and two down-regulated genes JUN and FOS, which are closely related to the development of PLA2R-associated IMN. Pathway enrichment analysis found that the biological process induced by VEGFA is associated with PI3K/Akt signalling. GSEA showed that the signalling pathway of DEGs in GSE115857 was focused on angiogenesis, in which VEGFA acts as a core gene. We confirmed the high expression of VEGFA, PI3K, and AKT in IMN renal biopsy samples with immunohistochemistry. In HVECs, we found that BV suppresses cell viability in a time and dose dependent manner. In vivo, we found low dose of BV attenuates proteinuria via inhibiting VEGFA/PI3K/AKT signalling. Meanwhile, low dose of BV alleviates the thickening of the GBM. Conclusion VEGFA/PI3K/AKT signalling may play significant roles in the pathogenesis of IMN, which may provide new targets for the treatment of IMN.

It is conducive to the sustainable development of human beings in karst regions to research the mechanism of karst rocky desertification (KRD) expansion. Whether the large-scale KRD in southwestern China is caused by climate change or human activities is still controversial. In this study, the evolution of the KRD in southwestern China over the past 2000 years was reconstructed through the high-precision δ13C record of stalagmites from Shijiangjun (SJJ) Cave, Guizhou Province, China. The δ13C of the stalagmites from SJJ Cave exhibited heavy values from the Medieval Warm Period (MWP) to the Little Ice Age (LIA). Furthermore, the δ13C records of other stalagmites and tufa from southwestern China also showed the same significant heavy trend. Because the stalagmite δ13C could record the change of ecological environment, it indicated that the consistent change of the stalagmites δ13C may record the process of KRD expansion in the karst regions of southwestern China. During the MWP, the stronger Asian summer monsoon and the northward movement of the rain belt led to a dry period in southwestern China and a wet period in northern China. In contrast, it was wet in southwestern China and dry in northern China during the LIA. In addition, after the Jing-Kang event (JK event, AD1127) occurred at the end of the Northern Song dynasty, the political and economic center of China migrated to southern China for the first time, which changed the population distribution pattern of larger population in the north and smaller population in the south. Therefore, the expansion of KRD in southwestern China was exacerbated in the MWP due to the change of climate in southwestern China, the migration of a large number of people, wars, the large-scale reclamation of arable land, and the cultivation of large areas of crops.

Clusters of water molecules have low ionization energies because of stabilization of charge from the dipole moment of surrounding molecules, and thus can form potential traps resulting in the undesirable photovoltaic performance in organic solar cells (OSCs). Herein, we demonstrated a solvent-water evaporation (SWE) strategy, which can effectively remove the water-induced traps that are omnipresent in photoactive layers, leading to a significant improvement in device performance. A higher power conversion efficiency of 17.10% and a better device photostability are achieved by using this SWE method, as compared with the untreated binary PM6:Y6 system (15.83%). We highlight the water-related traps as a limiting factor for carrier transport and extraction properties, and further reveal the good universality of the SWE strategy applied into OSCs. In addition, organic light-emitting diodes and organic field-effect transistors are investigated to demonstrate the applicability of this SWE approach. This strategy presents a major step forward for advancing the field of organic electronics.

The Himalaya–Hengduan Mountain (HHM) region consists of two global biodiversity hotspots characterized by a high degree of plant endemism. However, little is known about how these endemic species are formed and maintained in relation to the regional geomorphology of the past or current time. Thus, this study investigated the genetic structure of the herbaceous genus Acanthocalyx (Caprifoliaceae) endemic to the HHM to demonstrate if major geographic or ecological barriers in the HHM region have influenced its phylogeographic patterns. Our analyses revealed distinct genetic structures within A. alba and A. nepalensis and indicated that A. delavayi may have recently evolved from isolated peripheral populations of A. nepalensis. In particular, we not only confirmed a well-known genetic structure of alpine plants between the Himalayas and the Hengduan Mountains but also discovered a notable floristic boundary (bounded by 30° to 31°N latitude) within the Hengduan Mountains from A. alba. This study provides new insights into the dispersal and intraspecific genetic variation of Acanthocalyx and highlights the importance of geomorphological features for the diversification of HHM alpine flora.

Large zooplankton can efficiently graze on algae and thereby improve water quality. However, zooplankton body size is considered to decrease with decreasing latitude because of the high fish predation and warm temperatures at lower latitudes. To explore how fish stocking has destabilized the trophic cascade and influenced water quality along a latitudinal gradient of reservoirs, we compared zooplankton body size and trophic cascades to water quality indicators in the subtropical Lake Qiandaohu and in tropical Guangdong reservoirs. The results showed that the body length and total biomass of the dominant zooplankton in Lake Qiandaohu were much larger than those of zooplankton in the Guangdong reservoirs. Moreover, fish predation was the key factor influencing the changes in zooplankton body size and total biomass in Lake Qiandaohu. In the Guangdong reservoirs, water temperature and total phosphorus were the pivotal drivers of zooplankton body size and biomass, respectively. In addition, structural equation models showed that the decreasing zooplankton body size and biomass under fish pressure weakened the grazing pressure on phytoplankton and indirectly contributed to the low water clarity in Lake Qiandaohu. However, fish had little influence on the inefficient algal grazing of zooplankton in the Guangdong reservoirs. Overall, zooplankton can function as an indicator of water quality in fish-controlled subtropical reservoirs but not in nutrient-controlled tropical reservoirs.

Two-dimensional (2D) ferromagnets with out-of-plane (OOP) magnetic anisotropy are potential candidates for realizing the next-generation memory devices with ultra-low power consumption and high storage density. However, a scalable approach to synthesize 2D magnets with OOP anisotropy directly on the complimentary metal-oxide semiconductor (CMOS) compatible substrates has not yet been mainly explored, which hinders the practical application of 2D magnets. This work demonstrates a cascaded space confined chemical vapor deposition (CS-CVD) technique to synthesize 2D FexGeTe2 ferromagnets. The weight fraction of iron (Fe) in the precursor controls the phase purity of the as-grown FexGeTe2. As a result, high-quality Fe3GeTe2 and Fe5GeTe2 flakes have been grown selectively using the CS-CVD technique. Curie temperature (TC) of the as-grown FexGeTe2 can be up to ∼ 280 K, nearly room temperature. The thickness and temperature-dependent magnetic studies on the Fe5GeTe2 reveal a 2D Ising to 3D XY behavior. Also, Terahertz spectroscopy experiments on Fe5GeTe2 display the highest conductivity among other FexGeTe2 2D magnets. The results of this work indicate a scalable pathway for the direct growth and integration of 2D ternary magnets on CMOS-based substrates to develop spintronic memory devices.

Precision medicine means giving patients the right treatment at the right dose at the right time with minimum ill consequences and maximum efficacy. It is medicine personalized to the individual’s genes, environment, and lifestyle and, ultimately, its widespread use will require a deep understanding of the genomic variations that create predispositions or resistances to various diseases. Some of the links between genes and diseases are already known, and more are being discovered every day. Similarly, much is known about which drugs are efficacious for treating which diseases, but there is still more to learn. The issue now is how to extract this information from the biomedical literature in way that can keep pace with today’s rapid discoveries in medical research. Efforts to assemble an organized database of such knowledge to data have focused on mathematical statistic methods, computer-aided methods, etc. Success has been mixed as previous methods usually result in false positive or depend on training sample sets, lacking of generality in different research fields, which have choked advancements in precision medicine. To break through this bottleneck, we need novel methods that can extract and leverage the valuable information locked within the constraints of the data we have. Hence, in this paper, we present a new text-based computational framework for extracting full three-way drug-disease-gene triplet information related to colorectal cancer from biomedical texts. The framework consists of two main steps. The first is to construct an integrated drug-disease-gene network by extracting pair-wise associations between diseases, drugs, and genes, and then store unique drug-disease-gene triplets for further analysis. Since the constructed network is highly likely to be too sparse, the next step is to complete the incomplete links in the network, i.e., to predict novel links from genes to diseases to drugs. To validate our framework, we conducted a case study on colorectal cancer, mining the literature for drug-disease and disease-gene associations. An analysis of the subsequent inferences drawn between the two shows that this approach can help to inform novel research hypotheses and identify new knowledge triplets about various diseases, both of which are significant for the advancement and implementation of precision medicine.

Little is known about the influence of ambient fine particulate matter (PM2.5) on the incidence of venous thromboembolism in areas with heavy air pollution. We examined seasonal associations between airborne concentrations of fine particulate matter and outpatient visits for venous thromboembolism in Beijing using a city-wide time-series design that covered a period of 30 months (January 1, 2010 to June 30, 2012). Generalized additive models were used to investigate the associations with adjustment of temperature for various time lags (lag 0 for the warm season and lag 0-10 for the cold season). Overall, 92,435 outpatient visits were recorded by the Beijing Medical Claim Data for Employees database during the study period. We found a significant association between PM2.5 levels and outpatient visits for venous thromboembolism. A 10-μg/m3 increase in PM2.5 concentrations on lag days 0-2 corresponded to a 0.64% (95% confidence interval: 0.55-0.73%; P < 0.001) increase in outpatient visits for venous thromboembolism during the cold season, and a 10-μg/m3 increase in PM2.5 concentrations on lag days 0-3 corresponded to a 0.82% (95% confidence interval: 0.67-0.96%; P < 0.001) increase in outpatient visits for venous thromboembolism during the warm season. Our findings suggest that PM2.5 exposure is associated with outpatient visits for venous thromboembolism in Beijing, and a more pronounced association was observed during the warm season. We propose that various temperature-adjustment strategies should be used when investigating seasonal associations.

Purpose Due to the rarity of diffuse spinal cord astrocytoma, an effective model is still lacking to stratify their prognosis. Here, we aimed to establish a prognostic model through comprehensively evaluating clinicopathological features and preoperative peripheral blood inflammatory markers in 89 cases. Methods We performed univariate and multivariate Cox regression to identify prognosis factors. The Kaplan–Meier curves and ROC curves were employed to compare the prognostic value of selected factors. Results In addition to clinicopathological factors, we revealed the preoperative peripheral blood leukocyte count, neutrophils-to-lymphocytes ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were also significantly correlated with overall survival of spinal cord astrocytoma in univariate Cox regression, and NLR was still significant in multivariate Cox analysis. Further, we demonstrated that NLR ≤ 3.65 and preoperative McCormick score (MMS) ≤ 3 were independently correlated with better survival of WHO grade IV tumors. Meanwhile, Ki-67 3.65 or MMS = 4. Conclusion We successfully constructed a comprehensive prognostic model including preoperative peripheral blood inflammatory markers, which can stratify diffuse spinal cord astrocytoma into 4 subgroups.

We introduce an optical tweezer platform for assembling and individually manipulating a two-dimensional register of nuclear spin qubits. Each nuclear spin qubit is encoded in the ground $^{1}S_{0}$ manifold of $^{87}$Sr and is individually manipulated by site-selective addressing beams. We observe that spin relaxation is negligible after 5 seconds, indicating that $T_1\gg5$ s. Furthermore, utilizing simultaneous manipulation of subsets of qubits, we demonstrate significant phase coherence over the entire register, estimating $T_2^\star = \left(21\pm7\right)$ s and measuring $T_2^\text{echo}=\left(42\pm6\right)$ s., Comment: 10 pages, 4 figures