Three amphioxus reference genomes reveal gene and chromosome evolution of chordates.

The slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding of the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention, or rearrangements between descendants of whole-genome duplications, which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its three-dimensional chromatin architecture at the onset of zygotic activation and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.

The potential of mineral weathering of halophilic-endophytic bacteria isolated from Suaeda salsa and Spartina anglica.

Bacteria have the abilities of salt tolerant, mineral weathering and plant growth promoting can promote the growth of plants in saline lands. However, few reports of the mineral weathering capacity of halophilic-endophytic bacteria, raising the question of whether the halophilic-endophytic weathering bacteria are fundamentally distinct from those in plants communities. In this study, we isolated and characterized halophilic bacterial strains from the roots and leaves of Suaeda salsa and Spartina anglica with respect to their mineral weathering pattern, role in the promoting plant growth, community structure, and their changes in these two plants. Using improved Gibbson medium, we obtained 156 halophilic bacterial strains, among which 92 and 64 strains were isolated from the S. salsa and S. anglica samples, respectively. The rock weathering patterns of the isolates were characterized using batch cultures that measure the quantity of Si, Al, K, and Fe released from crystal biotite under aerobic conditions. Significantly, the biomass and capacity of the mineral weathering of the halophilic-endophytic bacteria were different in the plants. The abundance of the halophilic-endophytic bacterials in the Suaeda salsa was significantly greater than Spartina anglica, whereas the mineral weathering bacterial in the Suaeda salsa was similar to the Spartina anglica. Furthermore, the proportion of plant growth-promoting bacteria in the Suaeda salsa was higher than Spartina anglica. Phylogenetic analyses show that the weathered minerals were inhabited by specific functional groups of bacteria (Halomonas, Acinetobacter, Burkholderia, Alcaligenes, Sphingobium, Arthrobacter, Chryseobacterium, Paenibacillus, Microbacterium, Ensifer, Ralstonia and Enterobacter) that contribute to the mineral weathering. The changes in halophilic endophytes weathering communities between the two plants were attributable not only to major bacterial groups but also to a change in the minor population structure.

N-Doped carbon dots for the fluorescence and colorimetry dual-mode detection of curcumin.

Nitrogen doped carbon dots (N-CDs) were synthesized by a one-step hydrothermal method with dopamine and ethylenediamine. The as-prepared N-CDs were characterized via transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), fluorescence spectrophotometer, UV-Vis spectrophotometry and Fourier transform infrared spectroscopy (FTIR). The average particle dimension of the as-prepared N-CDs was 2.68 nm, and the best excitation and emission wavelengths were 405 nm and 535 nm, separately. N-CDs exhibits excellent selectivity and sensitivity to detect the curcumin (Cur), attaining a wider linear range of 97.5 nM-67.9 µM and a limit of detection (LOD) of as low as 94 nM. Interestingly, N-CDs can also give responsive signals of a visible colour change (yellow to red). Moreover, a novel fluorescent/colorimetric dual-mode method has been successfully employed for the determination of Cur in real samples with good recoveries (94%-110%) and precision (RSD = 0.3-2.9%).

LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/ß-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes.

BACKGROUND: Pancreatic cancer is one of the most lethal malignancies and has an extremely poor diagnosis and prognosis. The development of resistance to gemcitabine is still a major challenge. The long noncoding RNA PVT1 was reported to be involved in carcinogenesis and chemoresistance; however, the mechanism by which PVT1 regulates the sensitivity of pancreatic cancer to gemcitabine remains poorly understood. METHODS: The viability of pancreatic cancer cells was assessed by MTT assay in vitro and xenograft tumor formation assay in vivo. The expression levels of PVT1 and miR-619-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blotting analysis and qRT-PCR were performed to assess the protein and mRNA levels of Pygo2 and ATG14, respectively. Autophagy was explored via autophagic flux detection under confocal microscopy and autophagic vacuole investigation under transmission electron microscopy (TEM). The functional role and mechanism of PVT1 were further investigated by gain- and loss-of-function assays in vitro. RESULTS: In the present study, we demonstrated that PVT1 was up-regulated in gemcitabine-resistant pancreatic cancer cell lines. Gain- and loss-of-function assays revealed that PVT1 impaired sensitivity to gemcitabine in vitro and in vivo. We further found that PVT1 up-regulated the expression of both Pygo2 and ATG14 and thus regulated Wnt/ß-catenin signaling and autophagic activity to overcome gemcitabine resistance through sponging miR-619-5p. Moreover, we discovered three TCF/LEF binding elements (TBEs) in the promoter region of PVT1, and activation of Wnt/ß-catenin signaling mediated by the up-regulation of Pygo2 increased PVT1 expression by direct binding to the TBE region. Furthermore, PVT1 was discovered to interact with ATG14, thus promoting assembly of the autophagy specific complex I (PtdIns3K-C1) and ATG14-dependent class III PtdIns3K activity. CONCLUSIONS: These data indicate that PVT1 plays a critical role in the sensitivity of pancreatic cancer to gemcitabine and highlight its potential as a valuable target for pancreatic cancer therapy.

Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma.

Despite significant advances in therapy, the 5-year survival rates for patients with advanced stage oral cancers still remains poor as an appropriate treatment has not been found yet, due to side effects of chemo/radiotherapy. Verbascoside (VB), a major bioactive constituent of the Tsoong herb, displays pharmacological properties by exhibiting anti-oxidative, anti-inflammatory and anti-cancer activities. However, the underlining function and mechanism of VB in human oral squamous cell carcinoma (OSCC) remains unclear. In this study, we show that VB significantly decreased the viability and metastasis of HN4 and HN6 tumor cells, while promoting apoptosis. A xenograft OSCC mouse model further showed that intraperitoneal injection of VB strongly inhibited growth and lung metastasis of implanted tumor cells. Immunoblot analysis confirmed that VB effectively suppressed nuclear factor (NF)-κB activation and downstream Bcl-2/Bcl-XL expression, resulting in increased OSCC cell apoptosis. In addition, VB suppressed mRNA and protein expression of matrix metalloproteinase-9 via suppression of NF-κB activation, thereby inhibiting tumor cell metastasis. Inspiringly, compared to cisplatin-treated group, VB is a biocompatible agent without signficant side effects in vivo. Collectively, our results demonstrate that VB effectively inhibits OSCC tumor cell growth and metastasis via suppression of IκB kinase complex (IKK)/NF-κB-related signaling activation, suggesting that VB has potential use as a potent anticancer agent in OSCC therapeutic strategies.

Ice Squeezing Induced Multicolor Fluorescence Emissions from Polyacrylamide Cryogels.

Being short of conventional chromophores, polyacrylamide is generally not regarded as a fluorescent material. Exactly the polymerization of dilute solutions of acrylamide and N,N'-methylenebisacrylamide led to thick liquids at 60 °C, showing no fluorescence. Things changed when the phase transition of water was involved. The squeezing effect of ice crystals not only created polymeric solids (cryogels) at - 20 °C, but also endowed them unexpected fluorescence emissions. The macroporous cryogels are mainly blue fluorescent polymers. However yellow and red fluorescence were also achieved by changing the ingredient ratios. A series of instrumental detections revealed that the multicolor fluorescence were based on exquisite amido stacking induced from ice squeezing. If people make good use of the squeezing effect of the heaven-sent molecule to manipulate the interactions of monomer functionalities, cryogenic polymerization can be a promising method to produce diverse polymeric materials.

Resveratrol supplementation improves lipid and glucose metabolism in high-fat diet-fed blunt snout bream.

Here, we aimed to investigate whether resveratrol (RSV) can ameliorate high-fat diet (HFD)-induced metabolic disorder in fish. Blunt snout bream (Megalobrama amblycephala) with average weight 27.99 ± 0.56 g were fed a normal fat diet (NFD, 5% fat, w/w), a HFD (11% fat), or a HFD supplemented with 0.04, 0.36, or 1.08% RSV for 10 weeks. As expected, fish fed a HFD developed hepatic steatosis, as shown by elevated hepatic and plasma triglycerides, raised whole body fat, intraperitoneal fat ratio and hepatosomatic index, and increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST). RSV supplementation lessened increases in body mass, whole body fat, and intraperitoneal fat, and alleviated development of hepatic steatosis, elevations of plasma triglyceride and glucose, and abnormalities of ALT and AST in HFD-fed fish. RSV supplementation increased SIRT1 messenger RNA (mRNA) expression and consequently hepatic mRNA expression of adipose triglyceride lipase (ATGL), carnitine palmitoyltransferase (CPT1a), and microsomal triglyceride transfer protein (MTTP), implying upregulation of lipolysis, ß-oxidation, and lipid transport, respectively, in the liver. Conversely, hepatic lipoprotein lipase (LPL), sterol regulatory element-binding protein 1 (SREBP-1c), peroxisome proliferator-activated receptor γ (PPARγ), and ATP citrate lyase (ACLY) mRNA expression were decreased, implying suppression of fatty acid uptake, lipogenesis, and fatty acid synthesis. Additionally, RSV downregulated glucokinase (GCK) and sodium-dependent glucose cotransporter 1 (SGLT1) and upregulated glucose transporter 2 (GLUT2) mRNA expression, thus restoring normal glucose fluxes. Thus, RSV improves lipid and glucose metabolisms in blunt snout bream, which are potentially mediated by activation of SIRT1.

Depletion of abundant human serum proteins by per se imprinted cryogels based on sample heterogeneity.

Macroporous cryogels were prepared and used to deplete abundant proteins. It was accomplished based on the sample heterogeneity rather than any exogenous assistance. Human serum was added in monomer solutions to synthesize molecularly imprinted polymers; therein some abundant proteins were imprinted in the polyacrylamide cryogels. Meanwhile the rare components remained aqueous. Chromatography and electrophoresis showed that albumin, serotransferrin, and most globulins were depleted by columns packed with the molecularly imprinted polymers. After the depletion, lower abundance proteins were revealed by SDS-PAGE, peptide fingerprint analysis, and identified by MALDI-TOF-MS. This is an example that a "per se imprint" protocol enables to gradually dimidiate proteomes, simplify sample complexities, and facilitate further proteome profiling or biomarker discovery.

Shengxian decoction improves lung function in rats with bleomycin-induced idiopathic pulmonary fibrosis through the inhibition of PANoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Shengxian decoction (SXD) is a classic Chinese medicinal formula that can effectively improve clinical symptoms and quality of life and delay disease progression in idiopathic pulmonary fibrosis (IPF) patients; however, the underlying mechanisms remain unclear. AIM OF THE STUDY: This study aimed to observe PANoptosis in bleomycin-induced IPF and to assess the efficacy and mechanism of action of SXD in the treatment of IPF. MATERIALS AND METHODS: Fifty SD rats were randomly divided into the sham, IPF, IPF + pirfenidone (PFD), IPF + SXD-medium dose (SXD-M), and IPF + SXD-low dose (SXD-L) groups. Lung function analysis and microcomputed tomography imaging of the rats with IPF treated with oral pirfenidone or oral SXD for 28 days were performed. Hematoxylin and eosin (HE) staining and Masson's trichrome staining were used to observe pathological lung damage. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum levels of IL-1ß, IL-18, TNF-α, and IFN-γ. Pyroptosis, apoptosis, and necroptosis were assessed using TUNEL, TUNEL/caspase-1, and PI fluorescence staining, respectively. GSDMD, caspase-3, and MLKL were examined by immunohistochemistry. The expression of fibrin-, ZBP1-, pyroptosis-, apoptosis-, and necroptosis-related proteins in the lung tissue was determined by western blotting. RESULTS: SXD normalized lung function in rats with bleomycin-induced IPF and reduced serum inflammatory factor levels and lung tissue fibrosis. The underlying mechanism of action involves the inhibition of pyroptosis pathway proteins, such as NLRP3, caspase-1, cleaved caspase-1, and GSDMD; apoptotic pathway proteins, such as Bax, Bcl-2, cleaved caspase-3, and caspase-3; and necroptosis pathway proteins, such as RIPK1, RIPK3, p-MLKL and MLKL. These pathways are modulated by the PANoptosis initiator ZBP1. Notably, the efficacy of SXD is concentration dependent, with a medium dose exhibiting superior effectiveness compared to a low dose. CONCLUSION: Bleomycin induced PANoptosis in the lung tissue of rats with IPF. Additionally, SXD effectively delayed or reversed the early pathological changes in bleomycin-induced pulmonary fibrosis by inhibiting PANoptosis.

Construction of diagnostic models for the progression of hepatocellular carcinoma using machine learning.

Liver cancer is one of the most prevalent forms of cancer worldwide. A significant proportion of patients with hepatocellular carcinoma (HCC) are diagnosed at advanced stages, leading to unfavorable treatment outcomes. Generally, the development of HCC occurs in distinct stages. However, the diagnostic and intervention markers for each stage remain unclear. Therefore, there is an urgent need to explore precise grading methods for HCC. Machine learning has emerged as an effective technique for studying precise tumor diagnosis. In this research, we employed random forest and LightGBM machine learning algorithms for the first time to construct diagnostic models for HCC at various stages of progression. We categorized 118 samples from GSE114564 into three groups: normal liver, precancerous lesion (including chronic hepatitis, liver cirrhosis, dysplastic nodule), and HCC (including early stage HCC and advanced HCC). The LightGBM model exhibited outstanding performance (accuracy = 0.96, precision = 0.96, recall = 0.96, F1-score = 0.95). Similarly, the random forest model also demonstrated good performance (accuracy = 0.83, precision = 0.83, recall = 0.83, F1-score = 0.83). When the progression of HCC was categorized into the most refined six stages: normal liver, chronic hepatitis, liver cirrhosis, dysplastic nodule, early stage HCC, and advanced HCC, the diagnostic model still exhibited high efficacy. Among them, the LightGBM model exhibited good performance (accuracy = 0.71, precision = 0.71, recall = 0.71, F1-score = 0.72). Also, performance of the LightGBM model was superior to that of the random forest model. Overall, we have constructed a diagnostic model for the progression of HCC and identified potential diagnostic characteristic gene for the progression of HCC.

BRCA2, PALB2, RECQL4 Germline Pathogenic Variants, and Somatic TP53 Mutation in Triple Metachronous Malignancies: A Case Report and Literature Review.

Background: Multiple primary cancer (MPC) refers to the presence of more than one cancer in an individual. Triple primary malignancies are uncommon. Case: We report the case of a 50-year-old postmenopausal woman in our gynecology department, diagnosed with endometrial cancer, ovarian cancer, and unilateral breast cancer. She carried germline mutations in BRCA2, PALB2, and RECQL4, along with a somatic pathogenic variant in TP53. Endometrial cancer patients harboring germline pathogenic variants in BRCA2 exhibit a heightened risk of ovarian and breast cancer. BRCA2 is known to play a role in the development of ovarian and breast cancer, while PALB2 is identified as a gene associated with breast cancer susceptibility. RECQL4 has been linked to breast cancer, cervical cancer, and other tumors. Conclusion: Genetic testing may be imperative for identifying MPC in endometrial cancer patients. For individuals with BRCA2 and other gene pathogenic variants, routine examination and monitoring of the endometrium, ovaries, breasts, and other sites prone to polygenic cancer are recommended.

Sudden unexpected death in epilepsy: Investigation of autopsy-based studies.

Epilepsy is a common neurological disorder that is associated with increased morbidity and mortality. Sudden unexpected death in epilepsy (SUDEP) is one of the most common causes for epilepsy-related deaths and its characteristics remain largely unknown, particularly from a forensic autopsy perspective. The present study aimed to investigate the neurological, cardiac, and pulmonary findings for a total of 388 SUDEP decedents, encompassing three cases from our forensic center during 2011-2020 and 385 literature-reported autopsy cases. In the cases mentioned in this study, two of them presented with only mild cardiac abnormalities, such as focal myocarditis and mild coronary atherosclerosis of the left anterior coronary artery. The third one was negative of any pathological findings. After pooling together these SUDEP cases, we found that neurological changes (n = 218 cases, 56.2%) were the most common postmortem findings associated with SUDEP, with cerebral edema/congestion (n = 60 cases, 15.5%) and old traumatic brain injury (n = 58 cases, 14.9%) being the major findings. Interstitial fibrosis, myocyte disarray/hypertrophy, and mild coronary artery atherosclerosis were the most common findings related to primary cardiac pathology, documented in 49 (12.6%), 18 (4.6%), and 15 (3.9%) cases, respectively. Non-specific pulmonary edema was the major finding in the lungs. This is an autopsy-based study that reports the scenario of postmortem findings for SUDEP cases. Our study paves the way for understanding the pathogenesis of SUDEP and the interpretation of death.

Synthesis of Ni3S2 and MOF-Derived Ni(OH)2 Composite Electrode Materials on Ni Foam for High-Performance Supercapacitors.

Honeycomb-like Ni(OH)2/Ni3S2/Ni foam (NF) was fabricated via a two-step hydrothermal process and subsequent alkalization. Ni3S2 with a honeycombed structure was in-situ synthesized on the NF surface by a hydrothermal process. MOF-derived Ni(OH)2 nanosheets were then successfully grown on the Ni3S2/NF surface by a second hydrothermal process and alkaline treatment, and a large number of nanosheets were interconnected to form a typical honeycomb-like structure with a large specific surface area and porosity. As a binder-free electrode, the prepared honeycomb-like Ni(OH)2/Ni3S2/NF exhibited a high specific capacitance (2207 F·g-1 at 1 A·g-1, 1929.7 F·g-1 at 5 mV·s-1) and a remarkable rate capability and cycling stability, with 62.3% of the initial value (1 A·g-1) retained at 10 A·g-1 and 90.4% of the initial value (first circle at 50 mV·s-1) retained after 5000 cycles. A hybrid supercapacitor (HSC) was assembled with Ni(OH)2/Ni3S2/NF as the positive electrode and activated carbon (AC) as the negative electrode and exhibited an outstanding energy density of 24.5 Wh·kg-1 at the power density of 375 W·kg-1. These encouraging results render the electrode a potential candidate for energy storage.

MOF-Derived Ultrathin NiCo-S Nanosheet Hybrid Array Electrodes Prepared on Nickel Foam for High-Performance Supercapacitors.

At present, binary bimetallic sulfides are widely studied in supercapacitors due to their high conductivity and excellent specific capacitance (SC). In this article, NiCo-S nanostructured hybrid electrode materials were prepared on nickel foam (NF) by using a binary metal-organic skeleton as the sacrificial template via a two-step hydrothermal method. Comparative analysis was carried out with Ni-S and Co-S in situ on NF to verify the excellent electrochemical performance of bimetallic sulfide as an electrode material for supercapacitors. NiCo-S/NF exhibited an SC of 2081 F∙g-1 at 1 A∙g-1, significantly superior to Ni-S/NF (1520.8 F∙g-1 at 1 A∙g-1) and Co-S/NF (1427 F∙g-1 at 1 A∙g-1). In addition, the material demonstrated better rate performance and cycle stability, with a specific capacity retention rate of 58% at 10 A∙g-1 than at 1 A∙g-1, and 75.7% of capacity was retained after 5000 cycles. The hybrid supercapacitor assembled by NiCo-S//AC exhibited a high energy density of 25.58 Wh∙kg-1 at a power density of 400 W∙kg-1.

Integrating data dependent and data independent non-target screening methods for monitoring emerging contaminants in the Pearl River of Guangdong Province, China.

The occurrence of Contaminants of Emerging Concern (CECs) in the Pearl River of Guandong province, China, was characterized using a nontarget screening (NTS) strategy combining both data dependent and data independent acquisition techniques. Our analysis identified 620 unique compounds, including pharmaceuticals (137), pesticides (124), industrial materials (68), personal care products (32), veterinary drugs (27), plasticizers or flame retardants (11), etc. Out of these compounds, 40 CECs were found with a detection frequency of over 60 %, including diazepam, a well-known drug to treat anxiety, insomnia, convulsion, etc., which had the highest detection rate at 98 %. Risk quotients (RQs) were calculated for CECs identified with high confidence (Level 1, confirmed with authentic standards), and it was found that 12 CECs had RQs > 1, with notable concern for pretilachlor (detection frequency: 48 %; 0.8-19.0 ng/L), bensulfuron-methyl (86 %, 3.1-56.2 ng/L), imidacloprid (80 %, 5.3-62.8 ng/L) and thiamethoxam (86 %, 9.1-99.9 ng/L), which exhibited RQs exceeding the threshold of concern (RQ > 1) at 46-80 % of sampling sites. Additionally, tentative identification of potential structurally related compounds provided valuable insight into the parent-product relationships in complex samples. This study highlights the importance and urgency of using NTS for CECs in the environment and presents a novel data sharing approach, which facilitates other scientists to assess, investigate further, and perform retrospective analyses.

Brain-specific loss of Abcg1 disturbs cholesterol metabolism and aggravates pyroptosis and neurological deficits after traumatic brain injury.

Based on accumulating evidence, cholesterol metabolism dysfunction has been suggested to contribute to the pathophysiological process of traumatic brain injury (TBI) and lead to neurological deficits. As a key transporter of cholesterol that efflux from cells, the ATP-binding cassette (ABC) transporter family exerts many beneficial effects on central nervous system (CNS) diseases. However, there is no study regarding the effects and mechanisms of ABCG1 on TBI. As expected, TBI resulted in the different time-course changes of cholesterol metabolism-related molecules in the injured cortex. Considering ABCG1 is expressed in neuron and glia post-TBI, we generated nestin-specific Abcg1 knockout (Abcg1-KO) mice using the Cre/loxP recombination system. These Abcg1-KO mice showed reduced plasma high-density lipoprotein cholesterol levels and increased plasma lower-density lipoprotein cholesterol levels under the base condition. After TBI, these Abcg1-KO mice were susceptible to cholesterol metabolism turbulence. Moreover, Abcg1-KO exacerbated TBI-induced pyroptosis, apoptosis, neuronal cell insult, brain edema, neurological deficits, and brain lesion volume. Importantly, we found that treating with retinoid X receptor (RXR, the upstream molecule of ABCG1) agonist, bexarotene, in Abcg1-KO mice partly rescued TBI-induced neuronal damages mentioned above and improved functional deficits versus vehicle-treated group. These data show that, in addition to regulating brain cholesterol metabolism, Abcg1 improves neurological deficits through inhibiting pyroptosis, apoptosis, neuronal cell insult, and brain edema. Moreover, our findings demonstrate that the cerebroprotection of Abcg1 on TBI partly relies on the activation of the RXRalpha/PPARgamma pathway, which provides a potential therapeutic target for treating TBI.

Sudden Cardiac Death in Schizophrenia During Hospitalization: An Autopsy-Based Study.

Schizophrenia is a severe mental disorder that is often comorbid with heart dysfunction and even sudden cardiac death (SCD). Clinical studies of SCD in schizophrenia have been largely reported, while there are limited autopsy studies that directly showed whole-scale information of such events. In this study, we present nine autopsy-based SCD cases in schizophrenia patients who died suddenly during hospitalization. Their medical records before and during hospitalization, and postmortem autopsy findings were summarized. These decedents had an average duration of schizophrenia for 6.83 ± 3.75 years with a male/female ratio of 4:5. They were all on intermittent antipsychotics medication before hospitalization and died within 15 days after hospitalization. Seven of the nine cases (77.8%) died of organic heart diseases such as severe coronary artery atherosclerosis (n = 4), myocarditis (n = 1), cardiomyopathy (n = 1), and pulmonary thromboembolism (n = 1). Two cases remained unexplained after systemic autopsy and toxicological examinations. Postmortem autopsy identified hepatic steatosis (n = 6) and respiratory inflammation (n = 3) as the most common associate extra-cardiac lesions. Our data provided autopsy-based data of SCD cases in schizophrenia and highlighted an intensive care of such patients during hospitalization.

[Pollution Characteristics and Risk Assessment of Nitrated Polycyclic Aromatic Hydrocarbons in the Atmosphere of Guangdong-Hong Kong-Macao Greater Bay Area].

To investigate the pollution characteristics and sources of nitrated polycyclic aromatic hydrocarbons (NPAHs) in Guangdong-Hong Kong-Macao Greater Bay Area (GBA), 44 ambient air samples were collected using the active sampling method, which were then determined via gas chromatography-triple quadrupole tandem mass spectrometry. The main results showed that filters, polyurethane foam, and XAD-2 resin were the essential materials for sampling NPAHs in ambient air in order to characterize the pollution status accurately. The levels of ρ(Σ18NPAHs) in ambient air at GBA ranged from 162 pg·m-3 to 2094 pg·m-3, and the average levels of ρ(Σ18NPAHs) were (675±430) pg·m-3 in summer and (637±349) pg·m-3 in winter. NPAHs were widely found in the ambient air of GBA and were dominated by 1-nitronaphthalene (220 pg·m-3), 2-nitronaphthalene (146 pg·m-3), 9-nitroanthracene (105 pg·m-3), and 2-nitrofluoranthene (72 pg·m-3). The congener profile characteristics of NPAHs in summer and winter were similar. The gas/particle partitioning characteristics of NPAHs revealed that dicyclic and tricyclic NPAHs tend to occur in the gas phase, and tetracyclic NPAHs tend to be adsorbed in the particle phase. The fraction of NPAHs concentrations in the particulate fraction of their total atmospheric concentrations increased with the increase in their molecular weight. In winter, NPAHs tend to be adsorbed in the particle phase, whereas in summer, NPAHs tend to exist in the gas phase. Based on the ratios of characteristic pollutants, in both the summer and winter season, photochemical reactions were the main source of NPAHs in the atmosphere of GBA and were primarily generated by the reaction of the hydroxyl radical in the daytime. The carcinogenic risk value calculation showed that the current carcinogenic risk of NPAHs in the ambient air of GBA was controllable.

Restraint Stress Delays the Recovery of Neurological Impairments and Exacerbates Brain Damages through Activating Endoplasmic Reticulum Stress-mediated Neurodegeneration/Autophagy/Apopotosis post Moderate Traumatic Brain Injury.

Based on accumulating evidence, patients recovering from mild and moderate traumatic brain injury (TBI) often experience increased sensitivity to stressful events. However, few studies have assessed on the effects and pathophysiological mechanisms of stress on TBI. In the current study, using a mouse model of moderate TBI, we investigated whether restraint stress (RS) regulates secondary neurodegeneration and neuronal cell death, which are commonly associated with neurological dysfunctions. Our data showed that RS significantly reduced body weight recovery, delayed the recovery of neurological functions (motor function, cognitive function and anxiety-like behavior) and exacerbated the brain lesion volume after moderate TBI. Immunofluorescence results indicated that moderate TBI-induced cell insults and blood-brain barrier leakage were aggravated by RS. Further Western blotting experiments showed that RS activated endoplasmic reticulum (ER) stress excessively after moderate TBI and decreased the number of NeuN-positive cells, but increased the number of CHOP/NeuN-co-positive cells by performing immunostaining in the injured cortex after moderate TBI. Moreover, RS increased the ratios of CHOP/Aß and CHOP/p-Tau co-positive cells in the injured cortex after moderate TBI. However, blocking ER stress with the classic ER stress inhibitor salubrinal remarkably decreased apoptosis and the levels of autophagy-related proteins in the mouse model of moderate TBI plus RS. Collectively, RS delays the recovery of neurological function and deteriorates morphological damage by excessively activating ER stress-mediated neurodegeneration, apoptosis and autophagy after moderate TBI. Thus, monitoring stress levels in patients recovering from non-severe TBI may merit consideration in the future.

Interleukin-13 Affects the Recovery Processes in a Mouse Model of Hemorrhagic Stroke with Bilateral Tibial Fracture.

As one form of stroke, intracerebral hemorrhage (ICH) is a fatal cerebrovascular disease, which has high morbidity and mortality and lacks effective medical treatment. Increased infiltration of inflammatory cytokines coupled with pyroptotic cell death is involved in the pathophysiological process of ICH. However, little is known about whether concomitant fracture patients have the same progression of inflammation and pyroptosis. Hence, we respectively established the mouse ICH model and ICH with bilateral tibial fracture model (MI) to explore the potential cross-talk between the above two injuries. We found that MI obviously reversed the expressions of pyroptosis-associated proteins, which were remarkably up-regulated at the acute phase after ICH. Similar results were observed in neuronal expressions via double immunostaining. Furthermore, brain edema was also significantly alleviated in mice who suffered MI, when compared with ICH alone. To better clarify the potential mechanisms that mediated this cross-talk, recombinant mouse interleukin-13 (IL-13) was used to investigate its effect on pyroptosis in the mouse MI model, in which a lower level of IL-13 was observed. Remarkably, IL-13 administration re-awakened cell death, which was mirrored by the re-upregulation of pyroptosis-associated proteins and PI-positive cell counts. The results of hemorrhage volume and behavioral tests further confirmed its critical role in regulating neurological functions. Besides, the IL-13-treated MI group showed poor outcomes of fracture healing. To sum up, our research indicates that controlling the IL-13 content in the acute phase would be a promising target in influencing the outcomes of brain injury and fracture, and meanwhile, provides new evidence in repairing compound injuries in clinics.