Polyfluoroalkyl phosphate esters (PAPs) as PFAS substitutes and precursors: An overview.

Polyfluoroalkyl phosphate esters (PAPs) are emerging substitutes for legacy per- and polyfluoroalkyl substances (PFAS), which are widely applied in consumer products and closely related to people's daily lives. Increasing concern has been raised about the safety of PAPs due to their metabolism into perfluorooctanoic acid (PFOA) and other perfluorinated carboxylates (PFCAs) in vivo. This review summarizes the current knowledge on PAPs and highlights the knowledge gaps. PAPs dominated the PFAS profiles in wastewater, sludge, household dust, food-contact materials, paper products, paints, and cosmetics. They exhibit biomagnification due to their higher levels in top predators. PAPs have been detected in human blood worldwide, with the highest mean levels being found in the United States (1.9 ng/mL) and China (0.4 ng/mL). 6:2 diPAP is the predominant PAP among all identified matrices, followed by 8:2 diPAP. Toxicokinetic studies suggest that after entering the body, most PAPs undergo biotransformation, generating phase Ⅰ (i.e., PFCAs), phase II, and intermediate products with toxicity to be verified. Several epidemiological and toxicological studies have reported the antiandrogenic effect, estrogenic effect, thyroid disruption, oxidative damage, and reproductive toxicity of PAPs. More research is urgently needed on the source and fate of PAPs, human exposure pathways, toxicity other than reproductive and endocrine systems, toxic effects of metabolites, and mixed exposure effects.

Early differentiation of Casparian strip mediated by nitric oxide is required for efficient K transport under low K conditions in Arabidopsis.

The Casparian strip (CS) is a cell wall modification made of lignin that functions as an apoplastic barrier in the root endodermis to restrict nutrient and water transport between the soil and stele. CS formation is affected by nutritional conditions, and its physiological roles have been discussed. This study found that low K condition affects CS permeability, lignin deposition, and MYB36 mRNA accumulation. To understand the mechanism underlying these findings, we focused on nitric oxide (NO). NO is known to act as a signaling molecule and participates in cell wall synthesis, especially for lignin composition. However, the mechanism by which NO affects lignin deposition and corrects CS formation in the plant roots remains unclear. Through combining fluorescent observation with histological stains, we demonstrated that the root endodermal cell lignification response to low-potassium (K) conditions is mediated by NO through the MYB36-associated lignin-polymerizing pathway. Furthermore, we discovered the noteworthy ability of NO to maintain nutrient homeostasis for adaptation to low K conditions by affecting the correct apoplastic barrier formation of CS. Collectively, our results suggest that NO is required for the lignification and apoplastic barrier formation in the root endodermis during adaptation to low K conditions, which revealing the novel physiological roles of CS under low nutrient conditions and making a significant contribution to CS biology.

Environmental Exposure to Emerging Alternatives of Per- and Polyfluoroalkyl Substances and Polycystic Ovarian Syndrome in Women Diagnosed with Infertility: A Mixture Analysis.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been previously linked to polycystic ovarian syndrome (PCOS), but only a few legacy PFAS were examined. OBJECTIVES: This study aimed to explore this association with a variety of PFAS, including legacy, branched-chain isomers, and emerging alternatives, as well as a PFAS mixture. METHODS: From 2014 to 2016, we conducted a multicenter, hospital-based case-control study on environmental endocrine disruptors and infertility in China. Three hundred sixty-six women with PCOS-related infertility and 577 control participants without PCOS were included in the current analysis. Twenty-three PFAS, including 3 emerging PFAS alternatives, 6 linear and branched PFAS isomers, 6 short-chain PFAS, and 8 legacy PFAS, were quantified in the plasma. Logistic regression and two multipollutant models [quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods] were used to assess the association of individual PFAS and PFAS mixture with PCOS, as well as the potential interactions among the congeners. RESULTS: After adjusting for potential confounders, Each 1-standard deviation higher difference in ln-transformed 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) and hexafluoropropylene oxide dimer acid (HFPO-DA) level was significantly associated with a 29% (95% CI: 1.11, 1.52) and 39% (95% CI:1.16, 1.68) higher odds of PCOS, respectively. Meanwhile, branched isomers of perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) (i.e., br-PFHxS, n-PFOS, 1m-PFOS, Σ3,4,5m-PFOS), short-chain PFAS (i.e., PFPeS and PFHxA) and other legacy PFAS [i.e., total concentrations of PFOS (T-PFOS), and perfluorododecanoic acid (PFDoA)] were significantly associated with increased odds of PCOS. The PFAS mixture was positively related to PCOS in the BKMR model. A similar trend was observed in QGC model, a ln-unit increase in the PFAS mixture was associated with a 20% increased risk of PCOS [adjusted odds ratio (aOR)=1.20 (95% CI: 1.06, 1.37)]. After controlling for other PFAS homologs, 6:2 Cl-PFESA, HFPO-DA, Σ3,4,5m-PFOS, and PFDoA were the major contributors based on the QGC and BKMR models. The associations were more pronounced in overweight/obese women. CONCLUSIONS: In this group of women, environmental exposure to a PFAS mixture was associated with an elevated odds of PCOS, with 6:2 Cl-PFESA, HFPO-DA, Σ3,4,5m-PFOS, and PFDoA being the major contributors, especially in overweight/obese women. https://doi.org/10.1289/EHP11814.

Hyaline protoplasmic astrocytopathy in epilepsy.

Hyaline protoplasmic astrocytopathy (HPA) describes a rare histologic finding of eosinophilic, hyaline cytoplasmic inclusions in astrocytes, predominantly in the cerebral cortex. It has mainly been observed in children and adults with a history of developmental delay and epilepsy, frequently with focal cortical dysplasia (FCD), but the nature and significance of these inclusions are unclear. In this study, we review the clinical and pathologic features of HPA and characterize the inclusions and brain tissue in which they are seen in surgical resection specimens from five patients with intractable epilepsy and HPA compared to five patients with intractable epilepsy without HPA using immunohistochemistry for filamin A, previously shown to label these inclusions, and a variety of astrocytic markers including aldehyde dehydrogenase 1 family member L1 (ALDH1L1), SRY-Box Transcription Factor 9 (SOX9), and glutamate transporter 1/excitatory amino acid transporter 2 (GLT-1/EAAT2) proteins. The inclusions were positive for ALDH1L1 with increased ALDH1L1 expression in areas of gliosis. SOX9 was also positive in the inclusions, although to a lesser intensity than the astrocyte nuclei. Filamin A labeled the inclusions but also labeled reactive astrocytes in a subset of patients. The immunoreactivity of the inclusions for various astrocytic markers and filamin A as well as the positivity of filamin A in reactive astrocytes raise the possibility that these astrocytic inclusions may be the result of an uncommon reactive or degenerative phenomenon.

Dietary and maternal sociodemographic determinants of perfluoroalkyl and polyfluoroalkyl substance levels in pregnant women.

Diet, including drinking water, and demographic characteristics have been associated with PFAS exposure levels in the general population. But data in pregnant women are scarce. We aimed to examine the PFAS levels in relation to these factors in early pregnancy and included 2545 pregnant women in early pregnancy from the Shanghai Birth Cohort. Ten PFAS were measured using high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in plasma samples at around 14 weeks of gestation. Geometric mean (GM) ratios were used to estimate the associations between demographic characteristics, food intake and source of drinking water and concentrations of nine PFAS with a detection rate of at least 70%, and the total perfluoroalkyl carboxylic acids (∑PFCA), perfluoroalkyl sulfonic acids (∑PFSA) and all the PFAS concentrations (∑PFAS). Median concentrations of plasma PFAS ranged from 0.03 ng/mL for PFBS to 11.56 ng/mL for PFOA. In the multivariable linear models, maternal age, parity, parental education level, marine fish, freshwater fish, shellfish, shrimps, crabs, animal kidneys, animal liver, eggs, and bone soup in early pregnancy were positively associated with plasma concentrations of certain PFAS. Whereas pre-pregnancy BMI, plant-based foods, and drinking bottled water were negatively associated with some PFAS concentrations. In summary, this study suggested that fish and seafood, animal offal, and high-fat foods (eggs and bone soup) were significant sources of PFAS. PFAS exposure may be reduced by consuming more plant-based foods and potential interventions, such as drinking water treatment.

The relationship between canopy microclimate, fruit and seed yield, and quality in Xanthoceras sorbifolium.

Xanthoceras sorbifolium has high oil content and important biomass energy value, but its development is limited by the problem of low yield. This study investigated the relationship between the canopy microclimate, fruit yield, and fruit quality of Xanthoceras sorbifolium. Difference between the distributions of canopy microclimate factors as well as fruit and seed parameters in the inner and outer canopies of the lower layer, as well as between the inner and outer canopies of the upper layer, were investigated for a period of one year. Canopy structure induced significant differences between canopy microclimate factors during various periods of the year. Light intensity and temperature of the outer and upper canopies were higher than those of inner and lower canopies. However, relative humidity showed an opposing trend. Light intensity was significantly and positively correlated with fruit set percentage, fruit yield, and seed yield. Temperature was significantly and positively correlated with fruit yield and seed yield, but significantly negatively correlated with the oil concentration of seed kernels. Fruit and seed yields significantly decreased from the outer to the inner canopy and from the upper to the lower canopy. Fruit set percentage in the outer canopy was also significantly higher than that in the inner canopy. However, oil concentrations in the seed kernels of the lower layer were significantly higher than those of the upper layer. Additionally, regression analysis was used to construct evaluation models for microclimate, fruit, and seed parameters. Regression equations corresponding to the association between single microclimatic factors during different periods and the fruit and seed parameters may provide a reference for canopy pruning and help develop an optimal regression model that may be used to predict and estimate fruit and seed parameters.

A sensitive and robust method for the simultaneous determination of thirty-three legacy and emerging per- and polyfluoroalkyl substances in human plasma and serum.

Legacy and emerging per- and polyfluoroalkyl substances (PFAS) have attracted growing attention due to their potential adverse effects on humans. We developed a method to simultaneously determine thirty-three PFAS (legacy PFAS, precursors, and alternatives) in human plasma and serum using solid phase extraction coupled to ultra-performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS). The method yielded good linearity (>0.995) and excellent limits of detection (LODs) (0.0005~0.012 ng mL-1 in plasma and 0.002~0.016 ng mL-1 in serum). The relative recoveries ranged from 80.1 to 116%, with intra- and inter-day precision less than 14.3%. The robustness of this method has been tested continuously for 10 months (coefficients of variation <14.9%). Our method was successfully applied to the PFAS analysis of 42 real human plasma and serum samples collected from women. The proposed method is attractive for the biomonitoring of multi-class PFAS in human health risk assessment and epidemiological studies.

Reactive astrocytes transduce inflammation in a blood-brain barrier model through a TNF-STAT3 signaling axis and secretion of alpha 1-antichymotrypsin.

Astrocytes are critical components of the neurovascular unit that support blood-brain barrier (BBB) function. Pathological transformation of astrocytes to reactive states can be protective or harmful to BBB function. Here, using a human induced pluripotent stem cell (iPSC)-derived BBB co-culture model, we show that tumor necrosis factor (TNF) transitions astrocytes to an inflammatory reactive state that causes BBB dysfunction through activation of STAT3 and increased expression of SERPINA3, which encodes alpha 1-antichymotrypsin (α1ACT). To contextualize these findings, we correlated astrocytic STAT3 activation to vascular inflammation in postmortem human tissue. Further, in murine brain organotypic cultures, astrocyte-specific silencing of Serpina3n reduced vascular inflammation after TNF challenge. Last, treatment with recombinant Serpina3n in both ex vivo explant cultures and in vivo was sufficient to induce BBB dysfunction-related molecular changes. Overall, our results define the TNF-STAT3-α1ACT signaling axis as a driver of an inflammatory reactive astrocyte signature that contributes to BBB dysfunction.

Fatty acyl-CoA reductase influences wax biosynthesis in the cotton mealybug, Phenacoccus solenopsis Tinsley.

Mealybugs are highly aggressive to a diversity of plants. The waxy layer covering the outermost part of the integument is an important protective defense of these pests. However, the molecular mechanisms underlying wax biosynthesis in mealybugs remain largely unknown. Here, we analyzed multi-omics data on wax biosynthesis by the cotton mealybug, Phenacoccus solenopsis Tinsley, and found that a fatty acyl-CoA reductase (PsFAR) gene, which was highly expressed in the fat bodies of female mealybugs, contributed to wax biosynthesis by regulating the production of the dominant chemical components of wax, cuticular hydrocarbons (CHCs). RNA interference (RNAi) against PsFAR by dsRNA microinjection and allowing mealybugs to feed on transgenic tobacco expressing target dsRNA resulted in a reduction of CHC contents in the waxy layer, and an increase in mealybug mortality under desiccation and deltamethrin treatments. In conclusion, PsFAR plays crucial roles in the wax biosynthesis of mealybugs, thereby contributing to their adaptation to water loss and insecticide stress.

CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states.

Astrocytes become reactive in response to insults to the central nervous system by adopting context-specific cellular signatures and outputs, but a systematic understanding of the underlying molecular mechanisms is lacking. In this study, we developed CRISPR interference screening in human induced pluripotent stem cell-derived astrocytes coupled to single-cell transcriptomics to systematically interrogate cytokine-induced inflammatory astrocyte reactivity. We found that autocrine-paracrine IL-6 and interferon signaling downstream of canonical NF-κB activation drove two distinct inflammatory reactive signatures, one promoted by STAT3 and the other inhibited by STAT3. These signatures overlapped with those observed in other experimental contexts, including mouse models, and their markers were upregulated in human brains in Alzheimer's disease and hypoxic-ischemic encephalopathy. Furthermore, we validated that markers of these signatures were regulated by STAT3 in vivo using a mouse model of neuroinflammation. These results and the platform that we established have the potential to guide the development of therapeutics to selectively modulate different aspects of inflammatory astrocyte reactivity.

A New Product of Bilirubin Degradation by H2O2 and Its Formation in Activated Neutrophils and in an Inflammatory Mouse Model.

Bilirubin (BR) is a tetrapyrrolic compound stemming from heme catabolism with diverse physiological functions. It can be oxidized by H2O2 to form several degradation products, some of which have been detected in vivo and may contribute to the pathogenesis of certain diseases. However, the oxidative degradation of BR is complex and the conditions that BR degradation occurs pathophysiologically remain obscure. Neutrophils are known to generate large amounts of reactive oxygen species, including H2O2, upon activation and they are mobilized to inflammatory sites; therefore, we hypothesized that activated neutrophils could cause BR degradation, which could occur at inflammatory sites. In the present study, we investigated BR degradation by H2O2 and identified hematinic acid (BHP1) and a new product BHP2, whose structure was characterized as 2,5-diformyl-4-methyl-1H-pyrrole-3-propanoic acid. An LC-MS/MS method for the quantitation of the two compounds was then established. Using the LC-MS/MS method, we observed the concentration-dependent formation of BHP1 and BHP2 in mouse neutrophils incubated with 10 and 30 µM of BR with the yields being 16 ± 3.2 and 31 ± 5.9 pmol/106 cells for BHP1, and 25 ± 4.4 and 71 ± 26 pmol/106 cells for BHP2, respectively. After adding phorbol 12-myristate 13-acetate, a neutrophil agonist, to 30 µM of BR-treated cells, the BHP1 yield increased to 43 ± 6.6 pmol/106 cells, whereas the BHP2 one decreased to 47 ± 9.2 pmol/106 cells. The two products were also detected in hemorrhagic skins of mice with dermal inflammation and hemorrhage at levels of 4.5 ± 1.9 and 0.18 ± 0.10 nmol/g tissue, respectively, which were significantly higher than those in the non-hemorrhagic skins. BHP2 was neurotoxic starting at 0.10 µM but BHP1 was not, as assessed using Caenorhabditis elegans as the animal model. Neutrophil-mediated BR degradation may be a universally pathophysiological process in inflammation and can be particularly important under pathological conditions concerning hemorrhage.

Transcription factor network analysis identifies REST/NRSF as an intrinsic regulator of CNS regeneration in mice.

The inability of neurons to regenerate long axons within the CNS is a major impediment to improving outcome after spinal cord injury, stroke, and other CNS insults. Recent advances have uncovered an intrinsic program that involves coordinate regulation by multiple transcription factors that can be manipulated to enhance growth in the peripheral nervous system. Here, we use a systems genomics approach to characterize regulatory relationships of regeneration-associated transcription factors, identifying RE1-Silencing Transcription Factor (REST; Neuron-Restrictive Silencer Factor, NRSF) as a predicted upstream suppressor of a pro-regenerative gene program associated with axon regeneration in the CNS. We validate our predictions using multiple paradigms, showing that mature mice bearing cell type-specific deletions of REST or expressing dominant-negative mutant REST show improved regeneration of the corticospinal tract and optic nerve after spinal cord injury and optic nerve crush, which is accompanied by upregulation of regeneration-associated genes in cortical motor neurons and retinal ganglion cells, respectively. These analyses identify a role for REST as an upstream suppressor of the intrinsic regenerative program in the CNS and demonstrate the utility of a systems biology approach involving integrative genomics and bio-informatics to prioritize hypotheses relevant to CNS repair.

[Magnetic Resonance Imaging Manifestations of Rosai-Dorfman Disease in Central Nervous System].

Objective To investigate the clinical and magnetic resonance imaging(MRI) manifestations of Rosai-Dorfman disease(RDD) in central nervous system. Method The clinical and MRI data of 5 cases of RDD in central nervous system confirmed by pathology in the PLA General Hospital were analyzed retrospectively. Results The 5 cases included 4 males and 1 female,aged(39.8±21.7) years on average.Among them,4 cases were located in the intracranial area and 1 case in the thoracic spinal canal.The lesion showed isointense signal on T1 weighted image and iso,slight-hypo,and slight-hyperintense signals on T2 weighted image,and it presented intensively homogeneous enhancement in contrast-enhanced MRI.Two cases showed compressed brain area with edema around the left parietal and left frontotemporal dura,thickening and enhancement in the adjacent dura,and dural tail sign.Three cases presented bone destruction in adjacent diploe and thoracic vertebrae.One case showcased slight-hypo perfusion of the left parietal dura in arterial spin labeling. Conclusions RDD lesion usually appears as iso,slight hypo and slight hyper-intense signals on T2 weighted image and presents intensively homogeneous enhancement in contrast-enhanced MRI.The disease may involve the adjacent bone and the lesion shows slight hypo-perfusion on perfusion images.The MRI manifestations of RDD are characteristic,which are helpful for preoperative diagnosis and evaluation of RDD.

Divergent transcriptional regulation of astrocyte reactivity across disorders.

Astrocytes respond to injury and disease in the central nervous system with reactive changes that influence the outcome of the disorder1-4. These changes include differentially expressed genes (DEGs) whose contextual diversity and regulation are poorly understood. Here we combined biological and informatic analyses, including RNA sequencing, protein detection, assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and conditional gene deletion, to predict transcriptional regulators that differentially control more than 12,000 DEGs that are potentially associated with astrocyte reactivity across diverse central nervous system disorders in mice and humans. DEGs associated with astrocyte reactivity exhibited pronounced heterogeneity across disorders. Transcriptional regulators also exhibited disorder-specific differences, but a core group of 61 transcriptional regulators was identified as common across multiple disorders in both species. We show experimentally that DEG diversity is determined by combinatorial, context-specific interactions between transcriptional regulators. Notably, the same reactivity transcriptional regulators can regulate markedly different DEG cohorts in different disorders; changes in the access of transcriptional regulators to DNA-binding motifs differ markedly across disorders; and DEG changes can crucially require multiple reactivity transcriptional regulators. We show that, by modulating reactivity, transcriptional regulators can substantially alter disorder outcome, implicating them as therapeutic targets. We provide searchable resources of disorder-related reactive astrocyte DEGs and their predicted transcriptional regulators. Our findings show that transcriptional changes associated with astrocyte reactivity are highly heterogeneous and are customized from vast numbers of potential DEGs through context-specific combinatorial transcriptional-regulator interactions.

Epidemiological trends and major risk attribution analysis of pancreatic cancer in China, Japan and South Korea from 1990 to 2019 / 中华消化外科杂志

Objective:To analyze the epidemiological trends and major risk attribution of pancreatic cancer in China, Japan and South Korea from 1990 to 2019.Methods:The descriptive epidemiological method was conducted. The overall incidence rate, mortality rate, age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of pancreatic cancer in China, Japan and South Korea from 1990 to 2019 were collected from the Global Burden of Disease (GBD) Database. Age-standardized rates were calculated based on the worldwide standardized population structure provided by GBD Database 2019. Observation indicators: (1) incidence and motality of pancreatic cancer in China, Japan and South Korea in 2019; (2) age-period-cohort model analysis of incidence and mortality rates of pancreatic cancer in China, Japan and South Korea from 1990 to 2019; (3) trends of ASIR and ASMR of pancreatic cancer in China, Japan and South Korea from 1990 to 2019; (4) trends of major risk attribution of pancreatic cancer related death in China, Japan and South Korea from 1990 to 2019. Count data were represented as absolute numbers, percentages and ratios. Joinpoint V.4.7.0.0 software was used to calculate the annual percentage change (APC), the average annual percentage change (AAPC) of incidence and mortality rates of pancreatic cancer in different time periods and 95% confidence interval (95% CI). The age-period-cohort model in STATA V.15.0 software was used to analyze the influence of different ages, periods and birth cohorts on the risk of onset and death of pancreatic cancer after controlling the other two variables, with the risk effect size described as relative risk (95% CI). Results:(1) Incidence and motality of pancreatic cancer in China, Japan and South Korea in 2019. In 2019, the incidence rate of pancreatic cancer in China increased from 0.07/100,000 among 15-19 years old to 64.01/100,000 among 85-89 years old, with increasing from 0.09/100,000 to 94.71/100,000 in males and from 0.04/100,000 to 47.47/100,000 in females. The mortality rate of pancreatic cancer in China increased from 0.04/100,000 among 15-19 years old to 79.58/100,000 among 85-89 years old, with increasing from 0.05/100,000 to 116.50/100,000 in males and from 0.03/100,000 to 59.69/100,000 in females. The incidence rate of pancreatic cancer in Japan increased from 0.03/100,000 among 15-19 years old to 162.26/100,000 among 85-89 years old, with increasing from 0.03/100,000 to 177.67/100,000 in males and from 0.04/100,000 to 153.67/100,000 in females. The mortality rate of pancreatic cancer in Japan increased from 0.02/100,000 among 15-19 years old to 154.88/100,000 among 85-89 years old, with increasing from 0.02/100,000 to 170.93/100,000 in males and from 0.02/100,000 to 145.94/100,000 in females. The incidence rate of pancreatic cancer in South Korea increased from 0.04/100,000 among 15-19 years old to 136.78/100,000 among 85-89 years old, with increasing from 0.03/100,000 to 153.78/100,000 in males and from 0.04/100,000 to 129.73/100,000 in females. The mortality rate of pancreatic cancer in South Korea increased from 0.02/100,000 among 15-19 years old to 135.98/100,000 among 85-89 years old, with increasing from 0.02/100,000 to 156.21/100,000 in males and from 0.02/100,000 to 127.59/100,000 in females. The peak incidence and mortality of pancreatic cancer in China were found in males aged 65-69 years, and the overall incidence and mortality of males in different age groups were higher than those of females in the same age group. In Japan, the peak incidence of pancreatic cancer occurred in females aged 80-84 years and the peak mortality occurred in males aged 75-79 years. The morbidity and mortality of males aged <80 years were higher than those of females in the same age group, while the morbidity and mortality of males aged ≥80 years were lower than those of females in the same age group. In South Korea, the peak incidence of pancreatic cancer occurred in females aged 80-84 years, and the peak mortality occurred in males aged 70-74 years. The morbidity and mortality of males aged <75 years were higher than those of females in the same age group, while the morbidity and mortality of males aged ≥75 years were lower than those of females in the same age group. (2) Age-period-cohort model analysis of incidence and mortality rates of pancreatic cancer in China, Japan and South Korea from 1990 to 2019. Age effect: after adjustment for the period and cohort effects, the risk of incidence and mortality rates of pancreatic cancer in both males and females of China, Japan and South Korea increased with age, which is more obvious in females than males, and more obvious in Japanese than Chinese and Korean populations. Period effect: after adjustment for age and cohort effects, the risk of incidence and mortality rates of pancreatic cancer in both males and females of China, Japan and South Korea increased from 1990 to 2019, with the period effect more significant in the Chinese population. Cohort effect: after adjustment for age and period effects, the risk of morbidity and mortality rates of pancreatic cancer decreased with the passage of birth cohort in China, Japan and South Korea. (3) Trends of ASIR and ASMR of pancreatic cancer in China, Japan and South Korea from 1990 to 2019. The ASIR and ASMR of pancreatic cancer in China increased yearly from 1990 to 2019, and the ASIR and ASMR in 2019 were 1.82 times and 1.79 times those in 1990, respectively. The ASIR and ASMR of pancreatic cancer in Japan showed a slowly increasing trend, and the ASIR and ASMR in 2019 were 1.09 times and 1.05 times those in 1990, respectively. The ASIR and ASMR of pancreatic cancer in South Korea increased firstly, then decreased, and slowly increased. From 1990 to 2019, the AAPC of ASIR of pancreatic cancer in China was 2.08% (95% CI as 1.91% to 2.24%, P<0.05) and AAPC of ASMR was 2.02% (95% CI as 1.86% to 2.19%, P<0.05). The AAPC of ASIR of pancreatic cancer in Japan was 0.28% (95% CI as 0.15% to 0.42%, P<0.05) and AAPC of ASMR was 0.13% (95% CI as 0.03% to 0.24%, P<0.05). The AAPC of ASIR of pancreatic cancer in South Korea was 0.50% (95% CI as 0.21% to 0.80%, P<0.05) and AAPC of ASMR was 0.15% (95% CI as -0.10% to 0.40%, P>0.05). (4) Trends of major risk attribution of pancreatic cancer related death in China, Japan and South Korea from 1990 to 2019. The main risk factors for pancreatic cancer related death in China, Japan and South Korea from 1990 to 2019 were smoking, high fasting glucose and high body mass index (BMI). The trend of pancreatic cancer related death, mainly attributed to smoking, showed that the proportion of Chinese males increased from 31.4% in 1990 to 34.1% in 2000, then decreased to 31.1% in 2015, and then showed a slow increase to 31.7% in 2019. The proportion of Chinese females increased from 6.7% in 1990 to 10.4% in 2005 and then dropped to 8.7% in 2019. The proportion of Japanese males decreased from 38.8% in 1990 to 26.9% in 2019 and the proportion of Japanese females decreased from 20.9% in 1990 to 14.8% in 2019. The proportion of South Korean males decreased from 37.5% in 1990 to 30.3% in 2019 and the proportion of South Korean females decreased from 12.6% in 1990 to 10.0% in 2019. The trend of pancreatic cancer related death proportion, mainly attributed to high fasting blood glucose, showed that the proportion of Chinese males increased from 5.9% in 1990 to 7.1% in 2019 and the propor-tion of Chinese females increased from 6.2% in 1990 to 6.8% in 2019. The proportion of Japanese males increased from 7.0% in 1990 to 7.7% in 2019 and the proportion of females increased from 5.0% in 1990 to 5.5% in 2019. The proportion of South Korean males increased from 6.8% in 1990 to 9.7% in 2019 and the proportion of females increased from 6.1% in 1990 to 8.2% in 2019. The trend of pancreatic cancer related deaths proportion, attributed mainly to high BMI, showed that the proportion of Chinese males increased from 1.3% in 1990 to 3.0% in 2019 and the proportion of females increased from 2.1% in 1990 to 4.3% in 2019. The proportion of Japanese males increased from 2.0% in 1990 to 2.4% in 2019 and the proportion of females increased from 3.1% in 1990 to 3.4% in 2019. The proportion of South Korean males increased from 1.9% in 1990 to 3.1% in 2019 and the proportion of females increased from 3.4% in 1990 to 4.3% in 2019. Conclusions:The incidence of pancreatic cancer in China may continue to rise but to be stable in Japan and South Korea. The incidence of pancreatic cancer in females, especially elderly women, needs more attention. Smoking remains the most critical risk factor for pancreatic cancer. More attention should also be paid to the increased risk of pancreatic cancer associated with high BMI and high fasting plasma glucose.

The complete chloroplast genome of Eurya loquaiana (Pentaphylacaceae).

The complete chloroplast (cp) genome of Eurya loquaiana Dunn. has been reported in this study. The cp genome has a total length of 157,218 bp with the typical quadripartite structure, containing two inverted repeats (IRs) of 25,883 bp separated by a large single-copy (LSC) region of 87,248 bp and a small single-copy (SSC) region of 18,204 bp. The whole cp genome of E. loquaiana contains 128 genes, including 83 protein-coding genes, 37 tRNAs genes, and 8 rRNAs. The phylogenetic result showed that E. loquaiana is sister to E. alate.

Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions.

Biomaterials hold promise for therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo, or about how such responses influence biomaterial function. Here, we probed these factors in mice using a platform of injectable hydrogels readily modified to present interfaces with different physiochemical properties to host cells. We found that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. We show that the nature and intensity of CNS FBRs are determined by definable properties that significantly influence hydrogel functions, including resorption and molecular delivery when injected into healthy brain or stroke injuries. Cationic interfaces elicit stromal cell infiltration, peripherally derived inflammation, neural damage and amyloid production. Nonionic and anionic formulations show minimal levels of these responses, which contributes to superior bioactive molecular delivery. Our results identify specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications.

A chromosome-level genome assembly provides new insights into paternal genome elimination in the cotton mealybug Phenacoccus solenopsis.

Mealybugs (Hemiptera: Pseudococcidae) are economically important agricultural pests with several compelling biological phenomena including paternal genome elimination (PGE). However, limited high-quality genome assemblies of mealybugs hinder a full understanding of this striking and unusual biological phenomenon. Here, we generated a chromosome-level genome assembly of cotton mealybug, Phenacoccus solenopsis, by combining Illumina short reads, PacBio long reads and Hi-C scaffolding. The assembled genome was 292.54 Mb with a contig N50 of 489.8 kb and a scaffold N50 of 49.0 Mb. Hi-C scaffolding assigned 84.42% of the bases to five chromosomes. A total of 110.75 Mb (37.9%) repeat sequences and 11,880 protein-coding genes were predicted. The completeness of the genome assembly was estimated to be 95.5% based on BUSCO genes. In addition, 27,086 (95.3%) full-length PacBio transcripts were uniquely mapped to the assembled scaffolds, suggesting the high quality of the genome assembly. We showed that cotton mealybugs lack differentiated sex chromosomes by analysing genome resequencing data of males and females. DAPI staining confirmed that one chromosome set in males becomes heterochromatin at an early embryo stage. Chromatin immunoprecipitation assays with sequencing analysis demonstrated that the epigenetic modifications H3K9me3 and H3K27me3 are distributed across the whole genome in males, suggesting that these two modifications might be involved in maintaining heterochromatin status. Both markers were more likely to be distributed in repeat regions, while H3K27me3 had higher overall enrichment. Our results provide a valuable genomic resource and shed new light on the genomic and epigenetic basis of PGE in cotton mealybugs.

Male mating and female postmating performances in cotton mealybug (Hemiptera: Pseudococcidae): effects of female density.

For insects, female density is closely related to reproductive output. However, little is known about the effects of female density on male mating and female postmating performances. Here, we explored the effects of female density in cotton mealybug, Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae), an invasive, rapidly spreading pest in Asia damaging multiple crops and horticultural plants. Using USB digital microscopes, we investigated the frequency, duration, and intervals of mating for males that were individually supplied with 1, 5, 10, and 15 females. We also evaluated the reproduction of mated females and the sex ratio of their offspring. As the female density increased, males mated with more females while substantially shortening mating intervals. Mating occurred actively at the densities of 10 and 15 females, where males mated four times on average, and some mated 6-9 times. However, mating duration and the observed reproductive parameters of females (preoviposition period, overall period from formation of ovisacs to female death, fecundity, and offspring sex ratio) did not differ significantly with female density. A weak trade-off existed between males' mating frequency and longevity, but there was no relationship between females' fecundity and longevity. In conclusion, despite their short lifespan, P. solenopsis males have a high mating capacity, and their mating frequency and intervals can be significantly affected by female density. In contrast, female density has little influence on females' postmating performance. Our findings indicate the significance of the reproductive biology and life history strategies for rapid establishment and population development of mealybugs in newly invaded regions.