Mechanism of the Visible-Light-Promoted C(sp3)-H Oxidation via Uranyl Photocatalysis.

Uranyl cation, as an emerging photocatalyst, has been successfully applied to synthetic chemistry in recent years and displayed remarkable catalytic ability under visible light. However, the molecular-level reaction mechanisms of uranyl photocatalysis are unclear. Here, we explore the mechanism of the stepwise benzylic C-H oxygenation of typical alkyl-substituted aromatics (i.e., toluene, ethylbenzene, and cumene) via uranyl photocatalysis using theoretical and experimental methods. Theoretical calculation results show that the most favorable reaction path for uranyl photocatalytic oxidation is as follows: first, hydrogen atom transfer (HAT) from the benzyl position to form a carbon radical ([R•]), then oxygen addition ([R•] + O2 → [ROO•]), then radical-radical combination ([ROO•] + [R•] → [ROOR] → 2[RO•]), and eventually [RO•] reduction to produce alcohols, of which 2° alcohol would further be oxidized to ketones and 1° would be stepwise-oxygenated to acids. The results of the designed verification experiments and the capture of reactive intermediates were consistent with those of theoretical calculations and the previously reported research that the active benzylic C-H would be stepwise-oxygenated in the presence of uranyl. This work deepens our understanding of the HAT mechanism of uranyl photocatalysis and provides important theoretical support for the relevant application of uranyl photocatalysts in organic transformation.

Identification of Sulfur-Containing Chlorinated Paraffin Structural Analogues in Human Serum: Origination from Biotransformation or Bioaccumulation?

Chlorinated paraffins (CPs) are manufactured and used in high quantities and have diverse structural analogues. It is generally recognized that sulfur-containing structural analogues of CPs are mainly derived from sulfate-conjugated phase II metabolism. In this study, we non-targeted identified three classes of sulfur-containing CP structural analogues (CPs-S) in human serum, including 44 CP sulfates (CPs-SO4H/CPs-SO4H-OH), 14 chlorinated benzene sulfates (CBs-SO4H), and 19 CP sulfite esters (CPs-SO3/CPs-S2O6), which were generated during the production of commercial mixtures of CPs and, thus, bioaccumulated via environmental exposures. We first wrote a program to screen CPs-S, which were baseline-separated from CPs according to their polar functional groups. Then, mass spectral analyses of alkalization-acidification liquid-liquid extracts of serum samples and Orbitrap mass spectrometry analyses in the presence and absence of tetraphenylphosphonium chloride (Ph4PCl), respectively, were performed to determine the ionization forms ([M + Cl]- or [M - H]-) of CPs-S. The presence of fragment ions (SO4H-, SO3-, SO2Cl-, and HSO3-) revealed the structures of CPs-S, which were validated by their detections in commercial mixtures of CPs. The estimated total concentrations of CPs-S in the human serum samples were higher than the concentrations of medium- and long-chain CPs. The profiles of CPs-S in human serum were similar to those detected in CP commercial mixtures and rats exposed to the commercial mixtures, but CPs-S were not detected in human liver S9 fractions or rat tissues after exposure to CP standards. These results, together with the knowledge of the processes used to chemically synthesize CPs, demonstrate that CPs-S in humans originates from environmental bioaccumulation.

Personal exposure to airborne organic pollutants and lung function changes among healthy older adults.

Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.

Novel scoring system incorporating lipoproteins to predict outcomes of epithelial ovarian cancer patients.

OBJECTIVE: Epithelial ovarian cancer is the most lethal gynecological malignancy worldwide. While common prognostic factors are identified, the impact of serum lipoproteins remains controversial. This retrospective cohort study aims to investigate the association between specific lipoprotein levels and prognosis. METHODS: Clinical data of 420 participants with epithelial ovarian cancer registered at Women's Hospital, School of Medicine, Zhejiang University, between January 2014 and April 2021 were included. Cox regression analyses and Kaplan-Meier methods were used to assess prognosis, estimated by hazard ratio (HR) with 95% confidence interval (CI). A novel prognostic model incorporating lipoproteins was developed for evaluating the prognosis. Meta-analysis was applied to assess the impact of low density lipoprotein cholesterol (LDL-C) on prognosis. RESULTS: Among 420 patients, those in advanced stages exhibited higher low density lipoprotein cholesterol (LDL-C) (p=0.008) and lower high density lipoprotein cholesterol (HDL-C) levels (p<0.001), with no significant differences in total cholesterol or triglyceride levels. Elevated LDL-C level was significantly associated with worse overall survival (HR 1.72; 95% CI 1.15 to 2.58; p=0.010) and progression free survival (HR 1.94; 95% CI 1.46 to 2.58; p<0.001), whereas higher HDL-C level was linked to better overall survival (HR 0.56; 95% CI 0.37 to 0.85; p=0.004) and progression free survival (HR 0.61; 95% CI 0.46 to 0.81; p<0.001). A novel prognostic model, low density lipoprotein cholesterol-high density lipoprotein cholesterol-fibrinogen-lactate dehydrogenase-prealbumin-Fe-stage (LH-FLPFS), was established to enhance prognostic predictive efficacy. The meta-analysis further suggested that higher LDL-C level was associated with worse overall survival (HR 1.82; 95% CI 1.39 to 2.38; p<0.001). CONCLUSIONS: In this study, preoperative LDL-C and HDL-C levels emerged as potential prognostic factors for ovarian cancer. Establishment of a novel prognostic model, LH-FLPFS, holds promise for significantly improving prognostic predictive efficacy.

Long intergenic non-coding RNA 01126 activates IL-6/JAK2/STAT3 pathway to promote periodontitis pathogenesis.

OBJECTIVES: Periodontitis seriously affects oral-related quality of life and overall health. Long intergenic non-coding RNA 01126 (LINC01126) is aberrantly expressed in periodontitis tissues. This study aimed to explore the possible pathogenesis of LINC01126 in periodontitis. METHODS: Inflammatory model of human gingival fibroblasts (HGFs) was established. Cell Counting Kit-8 (CCK-8), wound healing assay, and flow cytometry were utilized to detect biological roles of LINC01126. Binding site of miR-655-3p to LINC01126 and IL-6 was predicted. Then, subcellular localization of LINC01126 and the binding ability of miR-655-3p to LINC01126 and IL-6 in HGFs were verified. Hematoxylin-Eosin (H&E) staining and immunohistochemistry (IHC) staining were utilized to detect tissue morphology and proteins expression of clinical samples. RESULTS: LINC01126 silencing can alleviate cell inflammation induced by lipopolysaccharide derived from Porphyromonas gingivalis, reduce cell apoptosis, and promote cell migration. As a "sponge" for miR-655-3p, LINC01126 inhibits its binding to mRNA of IL-6, thereby promoting inflammation progression and JAK2/STAT3 pathway activation. Quantitative real-time PCR, Western Blot, and IHC results of clinical tissue samples further confirmed that miR-655-3p expression was down-regulated and IL-6/JAK2/STAT3 was abnormally activated in periodontitis tissues. CONCLUSIONS: In summary, serving as an endogenous competitive RNA of miR-655-3p, LINC01126 promotes IL-6/JAK2/STAT3 pathway activation, thereby promoting periodontitis pathogenesis.

Environmentally relevant concentration PFNA promotes degradation of SMAD7 to drive progression of ovarian cancer via TGF-ß/SMADs signaling pathway.

Perfluorononanoic acid (PFNA), an acknowledged environmental endocrine disruptor, is increasingly utilized as a substitute for perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Despite its growing use, limited research has been conducted to investigate its potential impact on tumorigenesis and progression, and the potential molecular mechanisms. Earlier studies linked perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure to breast and gynecological cancer progression in humans, lacking a clear understanding of the underlying mechanisms, notably in ovarian cancer. Our investigation into PFNA's effects at environmental concentrations (0.25-2 mM) showed no significant impact on cell proliferation but a notable increase in invasion and migration of ovarian cancer cells. This led to alterations in epithelial-mesenchymal transition (EMT) markers, including Claudin1, Vimentin, and Snail. Notably, PFNA exposure activated the TGF-ß/SMADs signaling pathway. Crucially, SMAD7 degradation through the ubiquitin-proteasome system emerged as PFNA's pivotal molecular target for inducing EMT, corroborated in mouse models. In summary, this study presented evidence that environmentally relevant concentrations of PFNA could induce SMAD7 degradation via the proteasome pathway, subsequently activating the TGF-ß/SMADs signaling pathway, and promoting EMT in ovarian cancer. These results illuminated the association between PFNA exposure and metastasis of ovarian cancer.

The key metabolic signatures and biomarkers of polycyclic aromatic hydrocarbon-induced blood glucose elevation in chinese individuals exposed to diesel engine exhaust.

Due to the complexity of environmental exposure factors and the low levels of exposure in the general population, identifying the key environmental factors associated with diabetes and understanding their potential mechanisms present significant challenges. This study aimed to identify key polycyclic aromatic hydrocarbons (PAHs) contributing to increased fasting blood glucose (FBG) concentrations and to explore their potential metabolic mechanisms. We recruited a highly PAH-exposed diesel engine exhaust testing population and healthy controls. Our findings found a positive association between FBG concentrations and PAH metabolites, identifying 1-OHNa, 2-OHPh, and 9-OHPh as major contributors to the rise in FBG concentrations induced by PAH mixtures. Specifically, each 10 % increase in 1-OHNa, 2-OHPh, and 9-OHPh concentrations led to increases in FBG concentrations of 0.201 %, 0.261 %, and 0.268 %, respectively. Targeted metabolomics analysis revealed significant alterations in metabolic pathways among those exposed to high levels of PAHs, including sirtuin signaling, asparagine metabolism, and proline metabolism pathway. Toxic function analysis highlighted differential metabolites involved in various dysglycemia-related conditions, such as cardiac arrhythmia and renal damage. Mediation analysis revealed that 2-aminooctanoic acid mediated the FBG elevation induced by 2-OHPh, while 2-hydroxyphenylacetic acid and hypoxanthine acted as partial suppressors. Notably, 2-aminooctanoic acid was identified as a crucial intermediary metabolic biomarker, mediating significant portions of the associations between the multiple different structures of OH-PAHs and elevated FBG concentrations, accounting for 16.73 %, 10.84 %, 10.00 %, and 11.90 % of these effects for 1-OHPyr, 2-OHFlu, the sum concentrations of 2- and 9-OHPh, and the sum concentrations of total OH-PAHs, respectively. Overall, our study explored the potential metabolic mechanisms underlying the elevated FBG induced by PAHs and identified 2-aminooctanoic acid as a pivotal metabolic biomarker, presenting a potential target for intervention.

Distinct effects of dilute acid prehydrolysate inhibitors on enzymatic hydrolysis and yeast fermentation.

The effects of dilute acid prehydrolysate from poplar were investigated and compared in the enzymatic hydrolysis, fermentation, and simultaneous saccharification fermentation (SSF) in this study. The improvement of enzymatic hydrolysis and fermentation with resin adsorption and surfactant addition has also been represented. A total of 16 phenolic alcohols, aldehydes, acids and 3 furan derivatives in the prehydrolysates were identified and quantified by gas chromatography/mass spectrometry (GC/MS). The degree of inhibition from the phenolic compounds (26.55%) in prehydrolysate on the enzymatic hydrolysis was much higher than carbohydrates-derived inhibitors (0.52-4.64%). Around 40% degree of inhibition was eliminated in Avicel enzymatic hydrolysis when 75% of prehydrolysates phenolic compounds were removed by resin adsorption. This showed distinguishing inhibition degrees of various prehydrolysate phenolic compounds. Inhibition of prehydrolysate on enzymatic hydrolysis was more dosage-dependent, while their suppression on the fermentation showed a more complicated mode: fermentation could be terminated by the untreated prehydrolysate, while a small number of prehydrolysate inhibitors even improved the glucose consumption and ethanol production in the fermentation. Correlated with this distinct inhibition modes of prehydrolysate, the improvement of Tween 80 addition in SSF was around 7.10% for the final ethanol yield when the glucose accumulation was promoted by 76.6%.

Enhanced blue-green response of nanoarray AlGaAs photocathodes for underwater low-light detection.

Underwater optical communication and low-light detection are usually realized via blue-green laser sources and blue-green light-sensitive detectors. Negative-electron-affinity AlGaAs photocathode is an ideal photosensitive material for ocean exploration due to its adjustable spectrum range, long working lifetime, and easy epitaxy of materials. However, compared with other photocathodes, the main problem of AlGaAs photocathode is its low quantum efficiency. Based on Spicer's three-step photoemission model, nanoarray structures are designed on the surface of AlGaAs photocathode to improve its quantum efficiency from two aspects of optical absorption and photoelectron transport. Through simulation, it is concluded that the cylinder with diameter of 120 nm and height of 600 nm is the best nanoarray structure, and its absorptance is always greater than 90% in the 445∼532 nm range. Moreover, the absorptance and quantum efficiency of the cylinder nanoarray AlGaAs photocathode are less affected by the incident angle. When the angle of incident light reaches 70°, the minimum absorptance and quantum efficiency are still 64.6% and 24.9%. In addition, the square or hexagonal arrangement pattern of the nanoarray has little effect on the absorptance, however, a reduction in the overall emission layer thickness will decrease the absorptance near 532 nm.

A review on the application of the exposome paradigm to unveil the environmental determinants of age-related diseases.

Age-related diseases account for almost half of all diseases among adults worldwide, and their incidence is substantially affected by the exposome, which is the sum of all exogenous and endogenous environmental exposures and the human body's response to these exposures throughout the entire lifespan. Herein, we perform a comprehensive review of the epidemiological literature to determine the key elements of the exposome that affect the development of age-related diseases and the roles of aging hallmarks in this process. We find that most exposure assessments in previous aging studies have used a reductionist approach, whereby the effect of only a single environmental factor or a specific class of environmental factors on the development of age-related diseases has been examined. As such, there is a lack of a holistic and unbiased understanding of the effect of multiple environmental factors on the development of age-related diseases. To address this, we propose several research strategies based on an exposomic framework that could advance our understanding-in particular, from a mechanistic perspective-of how environmental factors affect the development of age-related diseases. We discuss the statistical methods and other methods that have been used in exposome-wide association studies, with a particular focus on multiomics technologies. We also address future challenges and opportunities in the realm of multidisciplinary approaches and genome-exposome epidemiology. Furthermore, we provide perspectives on precise public health services for vulnerable populations, public communications, the integration of risk exposure information, and the bench-to-bedside translation of research on age-related diseases.

Spatially Resolved Co-Imaging of Polyhalogenated Xenobiotics and Endogenous Metabolites Reveals Xenobiotic-Induced Metabolic Alterations.

A large group of polyhalogenated compounds has been added to the list of persistent organic pollutants in a global convention endorsed by over 100 nations. Once entering the biotas, these pollutants are transported to focal sites of toxicological action and affected endogenous metabolites, which exhibited distinct tissue or organ distribution patterns. However, no study is available to achieve simultaneous mapping of the spatial distributions of xenobiotics and endogenous metabolites for clarifying the molecular mechanism of toxicities. Herein, we present a sensitive mass spectrometry imaging method─tetraphenyl phosphonium chloride-enhanced ionization coupled with air flow-assisted ionization-Orbitrap mass spectrometry─which simultaneously determined the spatial distributions of polyhalogenated xenobiotics and endogenous metabolites. The spatially resolved toxicokinetics and toxicodynamics of typical polyhalogenated compounds (chlorinated paraffins (CPs) and hexabromocyclododecane (HBCD)) were assessed in zebrafish. Co-imaging of polyhalogenated compounds and metabolites visualized the major accumulation organs and maternal transfer of HBCD and CPs, and it clarified the reproductive toxicity of HBCD. CPs were accumulated in the liver, heart, and brain and decreased the concentrations of polyamine/inosine-related metabolites and lipid molecules in these organs. HBCD accumulated in the ovary and was effectively transferred to eggs, and it also disrupted normal follicular development and impaired the production of mature eggs from the ovary by inhibiting expressions of the luteinizing hormone/choriogonadotropin receptor gene. The toxic effects of metabolic disruptions were validated by organ-specific histopathological examinations. These results highlight the necessity to assess the distributions and bioeffects of pollutants in a spatial perspective.

PPARγ As a Potential Target for Adipogenesis Induced by Fine Particulate Matter in 3T3-L1 Preadipocytes.

Mounting evidence has shown that ambient PM2.5 exposure is closely associated with the development of obesity, and adipose tissue represents an important endocrine target for PM2.5. In this study, the 3T3-L1 preadipocyte differentiation model was employed to comprehensively explore the adipogenic potential of PM2.5. After 8 days of PM2.5 exposure, adipocyte fatty acid uptake and lipid accumulation were significantly increased, and adipogenic differentiation of 3T3-L1 cells was promoted in a concentration-dependent manner. Transcriptome and lipidome analyses revealed the systematic disruption of transcriptional and lipid profiling at 10 µg/mL PM2.5. Functional enrichment and visualized network analyses showed that the peroxisome proliferator-activated receptor (PPAR) pathway and the metabolism of glycerophospholipids, glycerolipids, and sphingolipids were most significantly affected during adipocyte differentiation. Reporter gene assays indicated that PPARγ was activated by PM2.5, demonstrating that PM2.5 promoted adipogenesis by activating PPARγ. The increased transcriptional and protein expressions of PPARγ and downstream adipogenesis-associated markers (e.g., Fabp4 and CD36) were further cross-validated using qRT-PCR and western blot. PM2.5-induced adipogenesis, PPARγ pathway activation, and lipid remodeling were significantly attenuated by the supplementation of a PPARγ antagonist (T0070907). Overall, this study yielded mechanistic insights into PM2.5-induced adipogenesis in vitro by identifying the potential biomolecular targets for the prevention of PM2.5-induced obesity and related metabolic diseases.

Association of serum uric acid levels with cardiovascular and all-cause mortality in hypertensive patients in China: a cohort study.

PURPOSE: The present study aimed to assess the association of elevated serum uric acid (SUA) and hypouricemia with all-cause mortality and cardiovascular mortality in Chinese hypertensive patients. METHODS: In the present prospective cohort, 9325 hypertensive patients from Dongguan, China were enrolled from 2014 to 2018 for analysis. Participants were categorised by quintiles of SUA. The HRs and 95% CIs for the association between SUA, all-cause and cardiovascular mortality were evaluated using the multivariate Cox regression model. After adjusting for multiple confounders, restricted cubic spline analysis was conducted to demonstrate the shape of relationship. RESULTS: After a median follow-up of 4.18 years for 9325 participants, there were 409 (4.4%) and 151 (1.6%) reported cases of all-cause and cardiovascular mortality, respectively. By using the third quintile of SUA (6.68 mg/dL to <7.55 mg/dL for men, 5.63 mg/dL to <6.42 mg/dL for women) as reference, the highest quintiles of SUA were associated with an elevated risk of all cause (HR: 1.34, 95% CI 1.00 to 1.80) in the crude model, but the association was not significant after adjusting for multiple comparisons. The association between low SUA and mortality and the dose-response analysis on the non-linearity of SUA-mortality relationship were not statistically significant. CONCLUSIONS: Although the association between SUA levels, all-cause and cardiovascular disease mortality did not appear to be significant among Chinese hypertensive patients, the findings might be confounded by their medical conditions. Further studies are needed to verify the optimal SUA levels for hypertensive patients.

Short-term exposure to antimony induces hepatotoxicity and metabolic remodeling in rats.

Antimony (Sb) poses a significant threat to human health due to sharp increases in its exploitation and application globally, but few studies have explored the pathophysiological mechanisms of acute hepatotoxicity induced by Sb exposure. We established an in vivo model to comprehensively explore the endogenous mechanisms underlying liver injury induced by short-term Sb exposure. Adult female and male Sprague-Dawley rats were orally administrated various concentrations of potassium antimony tartrate for 28 days. After exposure, the serum Sb concentration, liver-to-body weight ratio, and serum glucose levels significantly increased in a dose-dependent manner. Body weight gain and serum concentrations of biomarkers of hepatic injury (e.g., total cholesterol, total protein, alkaline phosphatase, and the aspartate aminotransferase/alanine aminotransferase ratio) decreased with increasing Sb exposure. Through integrative non-targeted metabolome and lipidome analyses, alanine, aspartate, and glutamate metabolism; phosphatidylcholines; sphingomyelins; and phosphatidylinositols were the most significantly affected pathways in female and male rats exposed to Sb. Additionally, correlation analysis showed that the concentrations of certain metabolites and lipids (e.g., deoxycholic acid, N-methylproline, palmitoylcarnitine, glycerophospholipids, sphingomyelins, and glycerol) were significantly associated with hepatic injury biomarkers, indicating that metabolic remodeling may be involved in apical hepatotoxicity. Our study demonstrated that short-term exposure to Sb induces hepatotoxicity, possibly through a glycolipid metabolism disorder, providing an important reference for the health risks of Sb pollution.

Efficacy of various surgical approaches in treating hematospermia using transurethral seminal vesiculoscopy.

PURPOSE: To explore the efficacy of different approaches of seminal vesiculoscopy surgery and the predictive factors of good treatment outcome. MATERIALS AND METHODS: A retrospective analysis of 68 patients who underwent seminal vesiculoscopy for hematospermia in our hospital from January 2015 to January 2021. According to different surgical approaches, they were divided into three groups: natural ejaculatory ducts (method A, 45 cases), assisted transurethral resection/incision of ejaculatory ducts (method B, 14 cases), fenestration in prostatic utricle (method C, 9 cases). We analyzed the recurrence rate of the three surgical approaches and the predictive factors of treatment efficacy. RESULTS: The total recurrence rate after the seminal vesiculoscopy for hematospermia in this group was 32.35%. The postoperative recurrence rates of the three methods were 24.44% for method A, 50.00% for method B and 44.44% for method C, and there was no significant difference among the three methods (P > 0.05). The data of five predictors of 45 cases in method A group were included in the Univariate Logistic analysis, the results suggest that whether complicated with seminal tract stones/cysts was an effective predictor (OR 0.250, P = 0.022), which was still an effective predictor in the Multivariate Logistic analysis model (OR 0.244, P = 0.010). CONCLUSIONS: The Transurethral seminal vesiculoscopy technique demonstrates a low postoperative recurrence rate in treating hematospermia. Among the various approaches, the intraoperative use of natural orifices through the ejaculatory duct exhibits the lowest recurrence rate. Additionally, seminal tract stones/cysts effectively predict favorable postoperative outcomes.

Pred-SF: A Precipitation Prediction Model Based on Deep Neural Networks.

How to predict precipitation accurately and efficiently is the key and difficult problem in the field of weather forecasting. At present, we can obtain accurate meteorological data through many high-precision weather sensors and use them to forecast precipitation. However, the common numerical weather forecasting methods and radar echo extrapolation methods have insurmountable defects. Based on some common characteristics of meteorological data, this paper proposes a Pred-SF model for precipitation prediction in target areas. The model focuses on the combination of multiple meteorological modal data to carry out self-cyclic prediction and a step-by-step prediction structure. The model divides the precipitation prediction into two steps. In the first step, the spatial encoding structure and PredRNN-V2 network are used to construct the autoregressive spatio-temporal prediction network for the multi-modal data, and the preliminary predicted value of the multi-modal data is generated frame by frame. In the second step, the spatial information fusion network is used to further extract and fuse the spatial characteristics of the preliminary predicted value and, finally, output the predicted precipitation value of the target region. In this paper, ERA5 multi-meteorological mode data and GPM precipitation measurement data are used for testing to predict the continuous precipitation of a specific area for 4 h. The experimental results show that Pred-SF has strong precipitation prediction ability. Some comparative experiments were also set up for comparison to demonstrate the advantages of the combined prediction method of multi-modal data and the stepwise prediction method of Pred-SF.

Observing Dislocations Transported by Twin Boundaries in Al Thin Film: Unusual Pathways for Dislocation-Twin Boundary Interactions.

Twins are generally regarded as obstacles to dislocations in face-centered cubic metals and can modify individual dislocations by locking them in twin boundaries or obliging them to dissociate. Through in situ tensile experiments on Al thin film in a transmission electron microscope, we report a dynamic process of dislocations being transported by twin lamella via periodic twinning and detwinning at the atomic scale. Following this process, a 60° dislocation first transforms into a sessile step of the twin boundary, then migrates under stress as a step and finally reverts back into a 60° dislocation. Our results reveal a novel evolution route of dislocations by a dislocation-twin interaction where the twins act as transport vehicles rather than as obstacles. The potential implications of this mechanism on toughening are also discussed.

Tetraphenylphosphonium Chloride-Enhanced Ionization Coupled to Orbitrap Mass Spectrometry for Sensitive and Non-targeted Screening of Polyhalogenated Alkyl Compounds from Limited Serum.

Although many types of halogenated compounds are known to bioaccumulate in humans, few are routinely biomonitored and many have remained uncharacterized in human exposome studies due to a lack of high-sensitivity and high-resolution analytical methods. In this study, we discovered tetraphenylphosphonium chloride (Ph4PCl, 10 µM) as a simple additive to the mobile phase, which enhanced the ionizations of polyhalogenated alkyl compounds (such as organochlorinated pesticides [OCPs], chlorinated paraffins [CPs], dechlorane plus [DPs], and some brominated flame retardants [BFRs]) in the form [M + Cl]- and boosted mass spectrometry responses by an average of 1-3 orders of magnitude at a resolution of 140,000. Ph4PCl-enhanced ionization coupled with a halogenation-guided screening process was used to establish a sensitive and non-targeted method that required only single-step sample preparation and identified Cl- and/or bromine-containing alkyl compounds. The method enabled the identification of ∼700 polyhalogenated compounds from 200 µL of human serum, 240 of which were known compounds: 33 short-chain CPs, 52 median-chain CPs, 97 long-chain CPs, 22 very short-chain CPs (vSCCPs), 19 OCPs, 13 DPs, and 4 BFRs. We also identified 325 emerging contaminants (34 unsaturated CPs, 285 chlorinated fatty acid methyl esters [CFAMEs], and 6 chloro-bromo alkenes) and 130 new contaminants (114 oxygen-containing CPs, 2 hexachlorocyclohexane structural analogs, and 11 amino-containing and 3 nitrate-containing chlorinated compounds). The full scan results highlighted the dominance of CPs, CFAMEs, vSCCPs, and dichlorodiphenyltrichloroethanes in the serum samples. Ph4PCl-enhanced ionization enabled the sensitive and non-targeted identifications of polyhalogenated compounds in small volumes of biological fluid.

Eye-Preserving Therapies for Advanced Retinoblastoma: A Multicenter Cohort of 1678 Patients in China.

PURPOSE: This study attempted to estimate the impact of eye-preserving therapies for the long-term prognosis of patients with advanced retinoblastoma with regard to overall survival and ocular salvage. DESIGN: Retrospective cohort study covering all 31 provinces (38 retinoblastoma treating centers) of mainland China. PARTICIPANTS: One thousand six hundred seventy-eight patients diagnosed with group D or E retinoblastoma from January 2006 through May 2016. METHODS: Chart review was performed. The patients were divided into primary enucleation and eye-preserving groups, and they were followed up for survival status. The impact of initial treatment on survival was evaluated by Cox analyses. MAIN OUTCOME MEASURES: Overall survival and final eye preservation. RESULTS: After a median follow-up of 43.9 months, 196 patients (12%) died, and the 5-year overall survival was 86%. In total, the eyeball preservation rate was 48%. In this cohort, 1172 patients (70%) had unilateral retinoblastoma, whereas 506 patients (30%) had bilateral disease. For patients with unilateral disease, 570 eyes (49%) underwent primary enucleation, and 602 patients (51%) received eye-preserving therapies initially. During the follow-up (median, 45.6 months), 59 patients (10%) from the primary enucleation group and 56 patients (9.3%) from the eye-preserving group died. Multivariate Cox analyses indicated no significant difference in overall survival between the 2 groups (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.84; P = 0.250). For patients with bilateral disease, 95 eyes (19%) underwent primary enucleation, and 411 patients (81%) received eye-preserving therapies initially. During the follow-up (median, 40.1 months), 12 patients (13%) from the primary enucleation group and 69 patients (17%) from the eye-preserving group died. For bilateral retinoblastoma with the worse eye classified as group E, patients undergoing primary enucleation exhibited better overall survival (HR, 2.35; 95% CI, 1.10-5.01; P = 0.027); however, this survival advantage was not evident until passing 22.6 months after initial diagnosis. CONCLUSIONS: Eye-preserving therapies have been used widely for advanced retinoblastoma in China. Patients with bilateral disease whose worse eye was classified as group E and who initially underwent eye-preserving therapies exhibited a worse overall survival. The choice of primary treatment for advanced retinoblastoma should be weighed carefully.

Exploration of cross-talk and pyroptosis-related gene signatures and molecular mechanisms between periodontitis and diabetes mellitus via peripheral blood mononuclear cell microarray data analysis.

OBJECTIVES: This bioinformatics study is aimed at identifying cross-talk genes, pyroptosis-related genes, and related pathways between periodontitis (PD) and diabetes mellitus (DM), which includes type 1 diabetes (T1DM) and type 2 diabetes (T2DM). METHODS: GEO datasets containing peripheral blood mononuclear cell (PBMC) data of PD and DM were acquired. After batch correction and normalization, differential expression analysis was performed to identify the differentially expressed genes (DEGs). And cross-talk genes in the PD-T1DM pair and the PD-T2DM pair were identified by overlapping DEGs with the same trend in each pair. The weighted gene coexpression network analysis (WGCNA) algorithm helped locate the pyroptosis-related genes that are related to cross-talk genes. Receiver-operating characteristic (ROC) curve analysis confirmed the predictive accuracy of these hub genes in diagnosing PD and DM. The correlation between hub genes and the immune microenvironment of PBMC in these diseases was investigated by Spearman correlation analysis. The experimentally validated protein-protein interaction (PPI) and gene-pathway network were constructed. Subnetwork analysis helped identify the key pathway connecting DM and PD. RESULTS: Hub genes in the PD-T1DM pair (HBD, NLRC4, AIM2, NLRP2) and in the PD-T2DM pair (HBD, IL-1Β, AIM2, NLRP2) were identified. The similarity and difference in the immunocytes infiltration levels and immune pathway scores of PD and DM were observed. ROC analysis showed that AIM2 and HBD exhibited pleasant discrimination ability in all diseases, and the subnetwork of these genes indicated that the NOD-like receptor signaling pathway is the most potentially relevant pathway linking PD and DM. CONCLUSION: HBD and AIM2 could be the most relevant potential cross-talk and pyroptosis-related genes, and the NOD-like receptor signaling pathway could be the top candidate molecular mechanism linking PD and DM, supporting a potential pathophysiological relationship between PD and DM.