Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway.

Neuropeptide substance P (SP) belongs to a family of bioactive peptides and regulates many human diseases. This study aims to investigate the role and underlying mechanisms of SP in colitis. Here, activated SP-positive neurons and increased SP expression were observed in dextran sodium sulfate (DSS)-induced colitis lesions in mice. Administration of exogenous SP efficiently ameliorated the clinical symptoms, impaired intestinal barrier function, and inflammatory response. Mechanistically, SP protected mitochondria from damage caused by DSS or TNF-α exposure, preventing mitochondrial DNA (mtDNA) leakage into the cytoplasm, thereby inhibiting the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. SP can also directly prevent STING phosphorylation through the neurokinin-1 receptor (NK1R), thereby inhibiting the activation of the TBK1-IRF3 signaling pathway. Further studies revealed that SP alleviated the DSS or TNF-α-induced ferroptosis process, which was associated with repressing the cGAS-STING signaling pathway. Notably, we identified that the NK1R inhibition reversed the effects of SP on inflammation and ferroptosis via the cGAS-STING pathway. Collectively, we unveil that SP attenuates inflammation and ferroptosis via suppressing the mtDNA-cGAS-STING or directly acting on the STING pathway, contributing to improving colitis in an NK1R-dependent manner. These findings provide a novel mechanism of SP regulating ulcerative colitis (UC) disease.

Normobaric Hyperoxia Combined With Endovascular Treatment Based on Temporal Gradient: A Dose-Escalation Study.

BACKGROUND: Normobaric hyperoxia (NBO) has neuroprotective effects in acute ischemic stroke. Thus, we aimed to identify the optimal NBO treatment duration combined with endovascular treatment. METHODS: This is a single-center, randomized controlled, open-label, blinded-end point dose-escalation clinical trial. Patients with acute ischemic stroke who had an indication for endovascular treatment at Tianjin Huanhu Hospital were randomly assigned to 4 groups (1:1 ratio) based on NBO therapy duration: (1) control group (1 L/min oxygen for 4 hours); (2) NBO-2h group (10 L/min for 2 hours); (3) NBO-4h group (10 L/min for 4 hours); and (4) NBO-6h group (10 L/min for 6 hours). The primary outcome was cerebral infarction volume at 72 hours after randomization using an intention-to-treat analysis model. The primary safety outcome was the 90-day mortality rate. RESULTS: Between June 2022 and September 2023, 100 patients were randomly assigned to the following groups: control group (n=25), NBO-2h group (n=25), NBO-4h group (n=25), and NBO-6h group (n=25). The 72-hour cerebral infarct volumes were 39.4±34.3 mL, 30.6±30.1 mL, 19.7±15.4 mL, and 22.6±22.4 mL, respectively (P=0.013). The NBO-4h and NBO-6h groups both showed statistically significant differences (adjusted P values: 0.011 and 0.027, respectively) compared with the control group. Compared with the control group, both the NBO-4h and NBO-6h groups showed significant differences (P<0.05) in the National Institutes of Health Stroke Scale scores at 24 hours, 72 hours, and 7 days, as well as in the change of the National Institutes of Health Stroke Scale scores from baseline to 24 hours. Additionally, there were no significant differences among the 4 groups in terms of 90-day mortality rate, symptomatic intracranial hemorrhage, early neurological deterioration, or severe adverse events. CONCLUSIONS: The effectiveness of NBO therapy was associated with oxygen administration duration. Among patients with acute ischemic stroke who underwent endovascular treatment, NBO therapy for 4 and 6 hours was found to be more effective. Larger-scale multicenter studies are needed to validate these findings. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05404373.

Multi-functional integrated design of a copper foam-based cathode for high-performance lithium-oxygen batteries.

Lithium-oxygen batteries (LOBs) with extraordinarily high energy density are some of the most captivating energy storage devices. Designing an efficient catalyst system that can minimize the energy barriers and address the oxidant intermediate and side-product issues is the major challenge regarding LOBs. Herein, we have developed a new type of integrated cathode of Cu foam-supported hierarchical nanowires decorated with highly catalytic Au nanoparticles which achieves a good combination of a gas diffusion electrode and a catalyst electrode, contributing to the synchronous multiphase transport of ions, oxygen, and electrons as well as improving the cathode reaction kinetics effectively. Benefiting from such a unique hierarchical architecture, the integrated cathode delivered superior electrochemical performance, including a high discharge capacity of up to 11.5 mA h cm-2 and a small overpotential of 0.49 V at 0.1 mA cm-2, a favorable energy efficiency of 84.3% and exceptional cycling stability with nearly 1200 h at 0.1 mA cm-2 under a fixed capacity of 0.25 mA h cm-2. Furthermore, density functional theory (DFT) calculations further reveal the intrinsic direct catalytic ability to form/decompose Li2O2 during the ORR/OER process. As a consequence, this work provides an insightful investigation on the structural engineering of catalysts and holds great potential for advanced integrated cathode design for LOBs.

Enhanced biotoxicity by co-exposure of aged polystyrene and ciprofloxacin: the adsorption and its influence factors.

Microplastics (MPs), as emerging contaminants, usually experience aging processes in natural environments and further affect their interactions with coexisted contaminants, resulting in unpredictable ecological risks. Herein, the effect of MPs aging on their adsorption for coexisting antibiotics and their joint biotoxicity have been investigated. Results showed that the adsorption capacity of aged polystyrene (PS, 100 d and 50 d) for ciprofloxacin (CIP) was 1.10-4.09 times higher than virgin PS due to the larger BET surface area and increased oxygen-containing functional groups of aged PS. Following the increased adsorption capacity of aged PS, the joint toxicity of aged PS and CIP to Shewanella Oneidensis MR-1 (MR-1) was 1.03-1.34 times higher than virgin PS and CIP. Combined with the adsorption process, CIP posed higher toxicity to MR-1 compared to aged PS due to the rapid adsorption of aged PS for CIP in the first 12 h. After that, the adsorption process tended to be gentle and hence the joint toxicity to MR-1 was gradually dominated by aged PS. A similar transformation between the adsorption rate and the joint toxicity of PS and CIP was observed under different conditions. This study supplied a novel perception of the synergistic effects of PS aging and CIP on ecological health.

A cleaved adhesin DNA vaccine targeting dendritic cell against Porphyromonas gingivalis-induced periodontal disease.

BACKGROUND: Arg-gingipain A (RgpA) is the primary virulence factor of Porphyromonas gingivalis and contains hemagglutinin adhesin (HA), which helps bacteria adhere to cells and proteins. Hemagglutinin's functional domains include cleaved adhesin (CA), which acts as a hemagglutination and hemoglobin-binding actor. Here, we confirmed that the HA and CA genes are immunogenic, and using adjuvant chemokine to target dendritic cells (DCs) enhanced protective autoimmunity against P. gingivalis-induced periodontal disease. METHODS: C57 mice were immunized prophylactically with pVAX1-CA, pVAX1-HA, pVAX1, and phosphate-buffered saline (PBS) through intramuscular injection every 2 weeks for a total of three administrations before P. gingivalis-induced periodontitis. The DCs were analyzed using flow cytometry and ribonucleic acid sequencing (RNA-seq) transcriptomic assays following transfection with CA lentivirus. The efficacy of the co-delivered molecular adjuvant CA DNA vaccine was evaluated in vivo using flow cytometry, immunofluorescence techniques, and micro-computed tomography. RESULTS: After the immunization, both the pVAX1-CA and pVAX1-HA groups exhibited significantly elevated P. gingivalis-specific IgG and IgG1, as well as a reduction in bone loss around periodontitis-affected teeth, compared to the pVAX1 and PBS groups (p < 0.05). The expression of CA promoted the secretion of HLA, CD86, CD83, and DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) in DCs. Furthermore, the RNA-seq analysis revealed a significant increase in the chemokine (C-C motif) ligand 19 (p < 0.05). A notable elevation in the quantities of DCs co-labeled with CD11c and major histocompatibility complex class II, along with an increase in interferon-gamma (IFN-γ) cells, was observed in the inguinal lymph nodes of mice subjected to CCL19-CA immunization. This outcome effectively illustrated the preservation of peri-implant bone mass in rats afflicted with P. gingivalis-induced peri-implantitis (p < 0.05). CONCLUSIONS: The co-administration of a CCL19-conjugated CA DNA vaccine holds promise as an innovative and targeted immunization strategy against P. gingivalis-induced periodontitis and peri-implantitis.

Plasma metabolites and risk of myocardial infarction: a bidirectional Mendelian randomization study.

BACKGROUND: Myocardial infarction (MI) is a critical cardiovascular event with multifaceted etiology, involving several genetic and environmental factors. It is essential to understand the function of plasma metabolites in the development of MI and unravel its complex pathogenesis. METHODS: This study employed a bidirectional Mendelian randomization (MR) approach to investigate the causal relationships between plasma metabolites and MI risk. We used genetic instruments as proxies for plasma metabolites and MI and conducted MR analyses in both directions to assess the impact of metabolites on MI risk and vice versa. In addition, the large-scale genome-wide association studies datasets was used to identify genetic variants associated with plasma metabolite (1400 metabolites) and MI (20,917 individuals with MI and 440,906 individuals without MI) susceptibility. Inverse variance weighted was the primary method for estimating causal effects. MR estimates are expressed as beta coefficients or odds ratio (OR) with 95% CI. RESULTS: We identified 14 plasma metabolites associated with the occurrence of MI (P < 0.05), among which 8 plasma metabolites [propionylglycine levels (OR = 0.922, 95% CI: 0.881-0.965, P < 0.001), gamma-glutamylglycine levels (OR = 0.903, 95% CI: 0.861-0.948, P < 0.001), hexadecanedioate (C16-DC) levels (OR = 0.941, 95% CI: 0.911-0.973, P < 0.001), pentose acid levels (OR = 0.923, 95% CI: 0.877-0.972, P = 0.002), X-24546 levels (OR = 0.936, 95% CI: 0.902-0.971, P < 0.001), glycine levels (OR = 0.936, 95% CI: 0.909-0.964, P < 0.001), glycine to serine ratio (OR = 0.930, 95% CI: 0.888-0.974, P = 0.002), and mannose to trans-4-hydroxyproline ratio (OR = 0.912, 95% CI: 0.869-0.958, P < 0.001)] were correlated with a decreased risk of MI, whereas the remaining 6 plasma metabolites [1-palmitoyl-2-arachidonoyl-GPE (16:0/20:4) levels (OR = 1.051, 95% CI: 1.018-1.084, P = 0.002), behenoyl dihydrosphingomyelin (d18:0/22:0) levels (OR = 1.076, 95% CI: 1.027-1.128, P = 0.002), 1-stearoyl-2-docosahexaenoyl-GPE (18:0/22:6) levels (OR = 1.067, 95% CI: 1.027-1.109, P = 0.001), alpha-ketobutyrate levels (OR = 1.108, 95% CI: 1.041-1.180, P = 0.001), 5-acetylamino-6-formylamino-3-methyluracil levels (OR = 1.047, 95% CI: 1.019-1.076, P < 0.001), and N-acetylputrescine to (N (1) + N (8))-acetylspermidine ratio (OR = 1.045, 95% CI: 1.018-1.073, P < 0.001)] were associated with an increased risk of MI. Furthermore, we also observed that the mentioned relationships were unaffected by horizontal pleiotropy (P > 0.05). On the contrary, MI did not lead to significant alterations in the levels of the aforementioned 14 plasma metabolites (P > 0.05 for each comparison). CONCLUSIONS: Our bidirectional MR study identified 14 plasma metabolites associated with the occurrence of MI, among which 13 plasma metabolites have not been reported previously. These findings provide valuable insights for the early diagnosis of MI and potential therapeutic targets.

Right ventricular dyssynchrony for the prediction of prognosis in patients with systemic lupus erythematosus-aaociated pulmonary arterial hypertension: a study with two-dimensional speckle tracking.

Pulmonary arterial hypertension (PAH) is a common complication of systemic lupus erythematosus (SLE), and PAH can cause right ventricle (RV) remodel and dyssynchrony. The aim of this study was to explore the value of RV dyssynchrony in predicting adverse clinical events in patients with systemic lupus erythematosus-aaociated pulmonary arterial hypertension (SLE-PAH) using two-dimensional speckle tracking echocardiography (2D-STE). A total of 53 patients with SLE-PAH were enrolled in this study. The dyssynchrony of the RV (RV-SD6) was evaluated by 2D-STE. The clinical data of all participants were collected, and routine cardiac function parameters were measured by two-dimensional echocardiography, and analyzed for their correlation with RV-SD6. The predictive value of RV-SD6 in clinical adverse event was evaluated. RV-SD6 was negatively correlated with RV-FLS, RV-FAC, and TAPSE (r = - 0.788, r = - 0.363 and r = - 0.325, respectively, all P < 0.01), while the correlation with RV-FLS was the strongest. linear regression analysis showed that RV-FLS was an independent risk factor for RV-SD6 (ß = - 1.40, 95% CI - 1.65 ~ - 1.14, P < 0.001). Cox regression analysis showed that RV-SD6 was a predictor with clinical adverse events (HR = 1.03, 95% CI 1 ~ 1.06, P < 0.05). RV-SD6 was highly discriminative in predicting clinical adverse events (AUC = 0.764), at a cutoff of 51.10 ms with a sensitivity of 83.3% and specificity of 68.3%. RV-FLS was negatively correlated with RV-SD6 and was an independent risk factor for it. RV-SD6 can serve as an indicator for predicting the occurrence of adverse clinical events in SLE-PAH patients, with high sensitivity and specificity.

Emerging lead-free all inorganic perovskite single crystals K7Bi3X16 (X = Cl, Br) toward photodetector application.

Lead-free inorganic perovskites have attracted intensive attention in the field of photodetectors owing to their high stability, non-toxicity, and remarkable photoelectric characteristics. Herein, we designed and developed a series of thus-far unreported lead-free all inorganic perovskite single crystals, K7Bi3X16 (X = Cl, Br). In particular, we resorted to cooling crystallization and intercalated K+ to inorganic Bi-Br and Bi-Cl frameworks as inorganic A-site cations, obtaining zero-dimensional (0D) K7Bi3X16 (X = Cl, Br) perovskite single crystals, which display suitable bandgaps, excellent electron mobility and low trap-state density, as analysed by experimental characterization and density functional theory (DFT) calculations. Accordingly, the vertical structure K7Bi3Br16 photodetector can achieve a fast ON/OFF switch under the irradiation of 395 nm light. When the light intensity is 5 mW cm-2 and the voltage is 3 V, the responsivity is calculated to be 0.052 mA W-1. The above characteristics make K7Bi3Br16 a promising material for fabricating ultraviolet photodetectors.

The African swine fever virus MGF300-4L protein is associated with viral pathogenicity by promoting the autophagic degradation of IKKß and increasing the stability of IκBα.

African swine fever (ASF) is a highly contagious, often fatal viral disease caused by African swine fever virus (ASFV), which imposes a substantial economic burden on the global pig industry. When screening for the virus replication-regulating genes in the left variable region of the ASFV genome, we observed a notable reduction in ASFV replication following the deletion of the MGF300-4L gene. However, the role of MGF300-4L in ASFV infection remains unexplored. In this study, we found that MGF300-4L could effectively inhibit the production of proinflammatory cytokines IL-1ß and TNF-α, which are regulated by the NF-κB signaling pathway. Mechanistically, we demonstrated that MGF300-4L interacts with IKKß and promotes its lysosomal degradation via the chaperone-mediated autophagy. Meanwhile, the interaction between MGF300-4L and IκBα competitively inhibits the binding of the E3 ligase ß-TrCP to IκBα, thereby inhibiting the ubiquitination-dependent degradation of IκBα. Remarkably, although ASFV encodes other inhibitors of NF-κB, the MGF300-4L gene-deleted ASFV (Del4L) showed reduced virulence in pigs, indicating that MGF300-4L plays a critical role in ASFV pathogenicity. Importantly, the attenuation of Del4L was associated with a significant increase in the production of IL-1ß and TNF-α early in the infection of pigs. Our findings provide insights into the functions of MGF300-4L in ASFV pathogenicity, suggesting that MGF300-4L could be a promising target for developing novel strategies and live attenuated vaccines against ASF.

Apical papilla stem cell-derived exosomes regulate lipid metabolism and alleviate inflammation in the MCD-induced mouse NASH model.

Stem cells from the apical papilla(SCAPs) exhibit remarkable tissue repair capabilities, demonstrate anti-inflammatory and pro-angiogenic effects, positioning them as promising assets in the realm of regenerative medicine. Recently, the focus has shifted towards exosomes derived from stem cells, perceived as safer alternatives while retaining comparable physiological functions. This study delves into the therapeutic implications of exosomes derived from SCAPs in the methionine-choline-deficient (MCD) diet-induced mice non-alcoholic steatohepatitis (NASH) model. We extracted exosomes from SCAPs. During the last two weeks of the MCD diet, mice were intravenously administered SCAPs-derived exosomes at two distinct concentrations (50 µg/mouse and 100 µg/mouse) biweekly. Thorough examinations of physiological and biochemical indicators were performed to meticulously evaluate the impact of exosomes derived from SCAPs on the advancement of NASH in mice induced by MCD diet. This findings revealed significant reductions in body weight loss and liver damage induced by the MCD diet following exosomes treatment. Moreover, hepatic fat accumulation was notably alleviated. Mechanistically, the treatment with exosomes led to an upregulation of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) levels in the liver, enhancing hepatic fatty acid oxidation and transporter gene expression while inhibiting genes associated with fatty acid synthesis. Additionally, exosomes treatment increased the transcription levels of key liver mitochondrial marker proteins and the essential mitochondrial biogenesis factor. Furthermore, the levels of serum inflammatory factors and hepatic tissue inflammatory factor mRNA expression were significantly reduced, likely due to the anti-inflammatory phenotype induced by exosomes in macrophages. The above conclusion suggests that SCAPs-exosomes can improve NASH.

rgpA-Engineered/Functionalized DNA Vaccine as a Novel Prophylactic Vaccination to Prevent Porphyromonas gingivalis-Induced Periodontitis: An in Vivo Study.

BACKGROUND: Arg-gingipain A (rgpA) and Arg-gingipain B (rgpB) are crucial virulence factors associated with Porphyromonas gingivalis (P. gingivalis) and have been recognized as promising targets for antibacterial vaccines. Although vaccines containing rgpA have shown efficacy, the incorporation of rgpB, which lacks the haemagglutinin adhesin (HA) domain, diminishes the vaccine's effectiveness. This study aims to assess the immunogenicity of the functional HA domain of rgpA in mouse periodontitis models. METHODS: A total of 24 mice were randomly divided into four groups, each receiving different immune injections: group A received phosphate-buffered saline (PBS) as an empty control; group B received pVAX1 as a negative control (NC); group C received pVAX1-HA; and group D received pVAX1-rgpA. The mice were subjected to intramuscular injections every two weeks for a total of three administrations. Prior to each immunization, blood samples were collected for antibody detection under isoflurane anesthesia. Following the final immunization, periodontitis was induced two weeks later by using sutures soaked in a P. gingivalis solution. The mice were euthanized after an additional two-week period. To assess the safety of the procedure, major organs were examined through hematoxylin-eosin (HE) staining. Subsequently, the levels of IgG, IgG1, and IgG2a in the serum were quantified via enzyme-linked immunosorbent assay (ELISA). Additionally, the expression of inflammatory factors in the gingiva, including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor alpha (TNF-α), was determined using quantitative real-time reverse transcript PCR (qRT-PCR). The extent of bone loss in periodontal tissues was evaluated using micro-computed tomography (micro-CT) and HE staining. RESULTS: HE staining of the organs confirmed the absence of vaccine-induced toxicity in vivo. After the second immunization, both the rgpA and HA groups displayed significantly higher specific IgG titers in comparison to the NC and PBS groups (p < 0.05). Furthermore, the rgpA and HA groups exhibited a noteworthy predominance of IgG1 antibodies after three immunization doses, while there was a noticeable reduction in IgG2a levels observed following ligation with P. gingivalis sutures, as opposed to the NC and PBS groups (p < 0.05). Additionally, both the HA and rgpA groups showed a significant decrease in the expression of inflammatory factors such as IL-6, IL-1ß, and TNF-α, as well as a reduction in bone loss around periodontitis-affected teeth, when compared to the NC and PBS groups (p < 0.05). CONCLUSIONS: The results of this study demonstrate that the rgpA-engineered/functionalized HA gene vaccine is capable of eliciting a potent prophylactic immune response against P. gingivalis-induced periodontitis, effectively serving as an immunogenic and protective agent in vivo.

The Activation of GABAAR Alleviated Cerebral Ischemic Injury via the Suppression of Oxidative Stress, Autophagy, and Apoptosis Pathways.

Ischemic stroke is a devastating disease leading to neurologic impairment. Compounding the issue is the very limited array of available interventions. The activation of a γ-aminobutyric acid (GABA) type A receptor (GABAAR) has been reported to produce neuroprotective properties during cerebral ischemia, but its mechanism of action is not yet fully understood. Here, in a rat model of photochemically induced cerebral ischemia, we found that muscimol, a GABAAR agonist, modulated GABAergic signaling, ameliorated anxiety-like behaviors, and attenuated neuronal damage in rats suffering cerebral ischemia. Moreover, GABAAR activation improved brain antioxidant levels, reducing the accumulation of oxidative products, which was closely associated with the NO/NOS pathway. Notably, the inhibition of autophagy markedly relieved the neuronal insult caused by cerebral ischemia. We further established an oxygen-glucose deprivation (OGD)-induced PC12 cell injury model. Both in vivo and in vitro experiments demonstrated that GABAAR activation obviously suppressed autophagy by regulating the AMPK-mTOR pathway. Additionally, GABAAR activation inhibited apoptosis through inhibiting the Bax/Bcl-2 pathway. These data suggest that GABAAR activation exerts neuroprotective effects during cerebral ischemia through improving oxidative stress and inhibiting autophagy and apoptosis. Our findings indicate that GABAAR serves as a target for treating cerebral ischemia and highlight the GABAAR-mediated autophagy signaling pathway.

Copper-zinc nanoparticle-decorated nitrogen-doped carbon composite for electrochemical determination of triclosan.

A new sensor based on copper-zinc bimetal embedded and nitrogen-doped carbon-based composites (CuZn@NC) was prepared for triclosan (TCS) detection by pyrolyzing the precursor of Cu-Zn binuclear metal-organic framework (MOF). The performance for detecting TCS was evaluated using linear scanning voltammetry (LSV) and differential pulse voltammetry (DPV), and the proton and electron numbers during TCS oxidation have been proved to be one-to-one. The results indicated that CuZn@NC can present a satisfactory analysis performance for TCS detection. Under the optimized conditions, the linear response range was 0.2-600 µM and the detection limit was 47.9 nM. The sensor presented good stability (signal current dropped only 2.5% after 21 days) and good anti-interference of inorganic salts and small molecular organic acids. The good recovery (97.5-104.1%) for detecting spiked TCS in commercial products (toothpaste and hand sanitizer) suggested its potential for routine determination of TCS in real samples.

The weakened physiological functions of human serum albumin in presence of polystyrene nanoplastics.

Due to the widespread presence of nanoplastics (NPs) in daily essentials and drinking water, the potential adverse effects of NPs on human health have become a global concern. Human serum albumin (HSA), the most abundant and multi-functional protein in plasma, has been chosen to understand the biological effects of NPs after entering the blood. The esterase activity and the transport of bisphenol A in the presence of polystyrene nanoplastics (PSNPs) under physiological conditions (pH 4.0 and 7.4) have been investigated to evaluate the possible biological effects. The interactions between PSNPs and HSA have also been systematically studied by multispectral methods and dynamic light scattering techniques. The esterase activity of HSA presented a decreased trend with increasing PSNPs; conversely, higher permeabilities are accompanied by higher amounts of PSNPs. Compared with the unchanged hydrodynamic diameter and weaker interactions at pH 7.4, stronger binding between HSA and PSNPs at pH 4.0 led to a significant increase in the particle size of the PSNPs-HSA complex. The quenching mechanism belonged to the static quenching type. The electrostatic force is proposed to be the dominant factor for PSNPs binding to HSA. The work provides some information about the toxicity of NPs when exposed to humans.

Spatiotemporal variations in soil pollution by polycyclic aromatic hydrocarbons over a 20-year economic boom in different districts of a heavy industrial city in North China.

Urbanization-related human activities, such as population aggregation, rapid industrial expansion, and intensified traffic, are key factors that impact local polycyclic aromatic hydrocarbon emissions and their associated health risks. Consequently, regions with varying degrees of urbanization within a megacity may exhibit diverse spatiotemporal patterns in the presence and distribution of soil polycyclic aromatic hydrocarbons, resulting in different levels of ecological risks for local inhabitants following the same period of development. In this study, we measured the concentrations of 16 polycyclic aromatic hydrocarbons in soil samples collected from industrial district and rural district in Tianjin (China) in 2018, and compared with polycyclic aromatic hydrocarbon data in 2001 from a previous study to characterize these regional variations in occurrence, source, and human risk of polycyclic aromatic hydrocarbons induced by urbanization with time and space. The results indicate the 20-year rapid urbanization and industrialization has differentially affected the composition, distribution and sources of polycyclic aromatic hydrocarbons in soils from different economic functional zones in Tianjin. Additionally, its impact on health risks in rural district appeared to be more significant than that in industrial district.

N6-methyladenosine-modified circPLPP4 sustains cisplatin resistance in ovarian cancer cells via PIK3R1 upregulation.

BACKGROUND: Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. METHODS: Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH. RESULTS: circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m6A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model. CONCLUSIONS: Our study reveals a plausible mechanism by which the m6A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.

More severe initial manifestations and worse short-term functional outcome of intracerebral hemorrhage in the plateau than in the plain.

Intracerebral hemorrhage (ICH) is one of the most devastating forms of stroke. However, studies on ICH at high altitude are insufficient. We aimed to compare the initial manifestations, imaging features and short-term functional outcomes of ICH at different altitudes, and further explore the effect of altitude on the severity and prognosis of ICH. We retrospectively recruited ICH patients from January 2018 to July 2021 from two centers at different altitudes in China. Information regarding to clinical manifestations, neuroimages, and functional outcomes at discharge were collected and analyzed. Association between altitude and initial severity, neuroimages, and short-term prognosis of ICH were also investigated. A total of 724 patients with 400 lowlanders and 324 highlanders were enrolled. Compared with patients from the plain, those at high altitude were characterized by more severe preliminary manifestations (P < 0.0001), larger hematoma volume (P < 0.001) and poorer short-term functional outcome (P < 0.0001). High altitude was independently associated with dependency at discharge (adjusted P = 0.024), in-hospital mortality (adjusted P = 0.049) and gastrointestinal hemorrhage incidence (adjusted P = 0.017). ICH patients from high altitude suffered from more serious initial manifestations and worse short-term functional outcome than lowlanders. Control of blood pressure, oxygen supplementation and inhibition of inflammation may be critical for ICH at high altitude.

[Effects of Apheresis Platelet Transfusion on PLT, MPV, PDW and PCT].

OBJECTIVE: To investigate the changes of platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) before and after apheresis platelet transfusion, the correlation between the parameters and their clinical significance. METHODS: A total of 38 patients who received apheresis platelet transfusion were selected, their results of blood routine test closest to the time point of apheresis platelet transfusion were consulted from hospital information system and the changes of PLT, PCT, MPV and PDW were compared before and after transfusion. The correlation between above parameters was analyzed. The correlation of body mass index (BMI) with the increased multiple and increased value after platelet infusion was also analyzed. RESULTS: Compared with pre-infusion, PLT and PCT significantly increased (both P <0.001) while MPV and PDW showed no significant difference after apheresis platelet transfusion (P >0.05). The difference of PLT and PCT before and after apheresis platelet transfusion had no correlation with PLT and PCT before transfusion (r =0.002, r =0.001), while the difference of MPV and PDW was negatively correlated with MPV and PDW before transfusion (r =-0.462, r =-0.610). The PLT growth rate was positively correlated with PCT growth rate before and after apheresis platelet transfusion (r =0.819). BMI was positively correlated with the increased multiple of PLT after infusion (r =0.721), but not with the increased value of PLT after infusion (r =0.374). CONCLUSION: Apheresis platelet transfusion can cause platelet parameters change and shows different characteristics. Characteristic changes of platelet parameters and their correlation can be used as reference indices to evaluate the efficacy of apheresis platelet transfusion.

Association and mediators between the impact of oral health-related quality of life and depression.

OBJECTIVES: Our research intended to explore the association and mediators (perceived social support and sleep quality) between the impact of oral health-related quality of life (OHRQoL) and depression among Chinese older adults. METHODS: A stratified, multi-stage random sampling approach was used in our study. A total of 3896 older individuals aged 60 years and older were included. Process macro 3.5 for SPSS was utilized for testing mediation hypotheses. RESULTS: The mean score of the OHRQoL of the elderly was 3.26 ± 7.15. The correlation coefficient between OHRQoL and depression was 0.25 (p < 0.001). Perceived social support (ß = 0.009, 95% CI = 0.006, 0.012) and sleep quality (ß = 0.073, 95% CI = 0.074, 0.093) mediated the relationship between OHRQoL and depression, respectively. The association between OHRQoL and depression was mediated sequentially by perceived social support and sleep quality (ß = 0.004, 95% CI = 0.002, 0.006). CONCLUSIONS: The participants reported relatively good OHRQoL. OHRQoL and depression showed a significant positive correlation. The relationship between OHRQoL and depression among Chinese seniors was mediated by perceived social support and sleep quality. Both directly and indirectly, OHRQoL can affect depression.

Large-capacity AC superimposed DC power supply for the degradation evaluation of DC-link capacitors.

The DC-link capacitor, whose operating voltage is a periodic irregular waveform, is a key device in the converter. A large-capacity DC/AC superimposed experimental power supply above 100 kVA is an important piece of equipment that must be used in the aging research of DC-link capacitors. The irregular periodic operating voltage of the DC support capacitor is equivalent in the form of DC voltage superimposed with multiple harmonics based on the Fast Fourier transform analysis. The power supply is mainly divided into four parts: an AC module, a DC module, a protection module, and an isolation component. The composited harmonics are output by the IGBT (Insulated Gate Bipolar Transistor) inverter of the AC module. The soft start method is applied to the AC module in order to ensure the long-term reliable operation of the power supply. The kV-level high-voltage is output by four inverter units connected in series. The amplitude and phase control of harmonic decomposition is adopted, and the inverter is controlled by Sinusoidal Pulse Width Modulation. The output voltage of the power supply is close to the operating voltage of the capacitor. Based on the designed power supply, the degradation experiment was carried out. The temperature rise and aging characteristics of DC-link capacitors under different AC/DC ratios were studied.