Unintentional emissions of polychlorinated naphthalenes in China: Sources, composition, and historical trends.

Polychlorinated naphthalenes (PCNs) are detrimental to human health and the environment. With the commercial production of PCNs banned, unintentional releases have emerged as a significant environmental source. However, relevant information is still scarce. In this study, provincial emissions for eight PCNs homologues from 37 sources in the Chinese mainland during the period of 1960-2019 were estimated based on a source-specific and time-varying emission factor database. The results showed that the total PCNs emissions in 2019 reached 757.0 kg with Hebei ranked at the top among all the provinces and iron & steel industry as the biggest source. Low-chlorinated PCNs comprised 90% of emissions by mass, while highly chlorinated PCNs dominated in terms of toxicity, highlighting divergent priorities for mitigating emissions and safeguarding human health. The emissions showed an overall upward trend from 1960 to 2019 driven by emission increase from iron & steel industry in terms of source, and from North China and East China in terms of geographic area. Per-capita emissions followed an inverted U-shaped environmental Kuznets curve while emission intensities decreased with increasing per-capita Gross Domestic Product (GDP) following a nearly linear pattern when log-transformed.

Palladium(0) and Brønsted Acid Co-catalyzed Enantioselective Hydro-Cyclization of 2,4-Dienyl Hydrazones and Oximes.

The transition metal-catalyzed asymmetric hydro-functionalization of 1,3-dienes has been well explored, but most reactions focus on electron-neutral substrates in an intermolecular manner. Here we first demonstrate that readily available 2,4-dienyl hydrazones and oximes can be efficiently utilized in the hydro-cyclization reaction under co-catalysis of a Brønsted acid and a chiral palladium complex, furnishing multifunctional dihydropyrazones and dihydroisoxazoles, respectively. Diverse substitution patterns for both types of electron-deficient diene compounds are tolerated, and corresponding heterocycles were generally constructed with moderate to excellent enantioselectivity, which can be elaborated to access products with higher molecular complexity and diversity. Control experiments and density functional theory calculations support that α-regioselective protonation of dienyl substrates by acid and concurrent π-Lewis base activation of Pd0 complex is energetically favoured in the formation of active π-allylpalladium intermediates, and an outer-sphere allylic amination or etherification mode is adopted to deliver the observed cyclized products enantioselectively.

Substantial contribution of transported emissions to organic aerosol in Beijing.

Haze in Beijing is linked to atmospherically formed secondary organic aerosol, which has been shown to be particularly harmful to human health. However, the sources and formation pathways of these secondary aerosols remain largely unknown, hindering effective pollution mitigation. Here we have quantified the sources of organic aerosol via direct near-molecular observations in central Beijing. In winter, organic aerosol pollution arises mainly from fresh solid-fuel emissions and secondary organic aerosols originating from both solid-fuel combustion and aqueous processes, probably involving multiphase chemistry with aromatic compounds. The most severe haze is linked to secondary organic aerosols originating from solid-fuel combustion, transported from the Beijing-Tianjing-Hebei Plain and rural mountainous areas west of Beijing. In summer, the increased fraction of secondary organic aerosol is dominated by aromatic emissions from the Xi'an-Shanghai-Beijing region, while the contribution of biogenic emissions remains relatively small. Overall, we identify the main sources of secondary organic aerosol affecting Beijing, which clearly extend beyond the local emissions in Beijing. Our results suggest that targeting key organic precursor emission sectors regionally may be needed to effectively mitigate organic aerosol pollution.

ITGB2 related to immune cell infiltration as a potential therapeutic target of inflammatory bowel disease using bioinformatics and functional research.

Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition regarded as a major risk factor for colitis-associated cancer. However, the underlying mechanisms of IBD remain unclear. First, five GSE data sets available in GEO were used to perform 'batch correction' and Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs). Candidate molecules were identified using CytoHubba, and their diagnostic effectiveness was predicted. The CIBERSORT algorithm evaluated the immune cell infiltration in the intestinal epithelial tissues of patients with IBD and controls. Immune cell infiltration in the IBD and control groups was determined using the least absolute shrinkage selection operator algorithm and Cox regression analysis. Finally, a total of 51 DEGs were screened, and nine hub genes were identified using CytoHubba and Cytoscape. GSE87466 and GSE193677 were used as extra data set to validate the expression of the nine hub genes. CD4-naïve T cells, gamma-delta T cells, M1 macrophages and resting dendritic cells (DCs) are the main immune cell infiltrates in patients with IBD. Signal transducer and activator of transcription 1, CCR5 and integrin subunit beta 2 (ITGB2) were significantly upregulated in the IBD mouse model, and suppression of ITGB2 expression alleviated IBD inflammation in mice. Additionally, the expression of ITGB2 was upregulated in IBD-associated colorectal cancer (CRC). The silence of ITGB2 suppressed cell proliferation and tumour growth in vitro and in vivo. ITGB2 resting DCs may provide a therapeutic strategy for IBD, and ITGB2 may be a potential diagnostic marker for IBD-associated CRC.

China's Modified Version of Sniffin' Sticks 12-Identification Test Used in Chinese Parkinson's Disease and Multiple System Patients: Comparison of Three Olfactory Testing Methods.

Objectives: The aim of this study was to compare the Sniffin' Sticks 12-identification test (SIT-12), China-modified version of the SIT-12 test (Ch-SIT-12) and brief smell identification test for Chinese (B-SITC) in Chinese population of Parkinson's disease (PD) and multiple system atrophy (MSA). Methods: 36 patients with PD and 7 patients with MSA were enrolled in this study. Three olfactory testing methods (SIT-12, Ch-SIT-12, and B-SITC) were used to test the olfactory function in all participants. Furthermore, demographic and clinical data were collected. Results: There was no significant difference between three olfactory tests in patients with PD (B-SITC vs. SIT-12: P=0.508; Ch-SIT-12 vs. B-SITC: P=0.146; and SIT-12 vs. Ch-SIT-12: P=0.375). Tremor-dominant (TD) subtypes have better olfactory function than akinetic-rigid dominant (ARD) subtypes when using Ch-SIT-12 (77.8% vs. 29.6%, P=0.019) or B-SITC (55.6% vs. 14.8%, P=0.026). There was a statistical difference between the PD and MSA using Ch-SIT-12 to test the olfactory function (P=0.046). Conclusions: Our results indicated that SIT-12, Ch-SIT-12 and B-SITC can be used for the detection of olfactory dysfunction in Chinese population of PD. TD subtypes may have better olfactory function than ARD subtypes. In addition, Ch-SIT-12 may be used to differentiate PD from MSA, but that should be confirmed in a larger population.

Intermittent Fasting Targets Osteocyte Neuropeptide Y to Relieve Osteoarthritis.

Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)- or natural aging-induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY-abundant culture medium of osteocytes (OCY-CM) from osteoarthritic mice possess pro-inflammatory, pro-osteoclastic, and pro-neurite outgrowth effects, while OCY-CM from the intermittent fasting-treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM-induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

Antagonistic interaction between caffeine and ketamine in zebrafish: Implications for aquatic toxicity.

The coexistence of caffeine (CF) and ketamine (KET) in surface waters across Asia has been widely reported. Previous studies have implied that CF and KET may share a mechanism of action. However, the combined toxicity of these two chemicals on aquatic organisms remains unclear at environmental levels, and the underlying mechanisms are not well understood. Here we demonstrate that KET antagonizes the adverse effects of CF on zebrafish larvae by modulating the gamma-aminobutyric acid (GABA)ergic synapse pathway. Specifically, KET (10-250 ng L-1) ameliorates the locomotor hyperactivity and impaired circadian rhythms in zebrafish larvae induced by 2 mg L-1 of CF, showing a dose-dependent relationship. Additionally, the developmental abnormalities in zebrafish larvae exposed to CF are mitigated by KET, with an incidence rate reduced from 26.7% to 6.7%. The competition between CF and KET for binding sites on the GABA-A receptor (in situ and in silico) elucidates the antagonistic interactions between the two chemicals. Following a seven-day recovery period, the adverse outcomes of CF exposure persist in the fish, whereas the changes observed in the CF + KET groups are significantly alleviated, especially with KET at 10 ng L-1. Based on these results, it is imperative to further assess the environmental risks associated with CF and KET co-pollution. This pilot study underscores the utility of systems toxicology approaches in estimating the combined toxicity of environmental chemicals on aquatic organisms. Moreover, the nighttime behavioral functions of fish could serve as a sensitive biomarker for evaluating the toxicity of psychoactive substances.

Proteomic and Phosphoproteomic analysis of thyroid papillary carcinoma: Identification of potential biomarkers for metastasis.

Thyroid cancer has emerged as the most rapidly proliferating solid neoplasm. In this study, we included a cohort of patients who underwent sonographic assessment and surgical intervention at the Sir Run Run Shaw Hospital, associated with the School of Medicine at Zhejiang University, spanning from January 2019 to June 2020. Stratification of cases was based on a combination of preoperative ultrasonographic evaluations and postoperative histopathological diagnoses, resulting in three distinct groups: high-risk papillary thyroid carcinoma (PTC) labeled as C1, low-risk PTC designated as C2, and a control group (N) composed of benign thyroid tissue adjacent to the carcinoma. Proteomic and phosphoproteomic analyses were conducted on PTC specimens. The comparative assessment revealed that proteins up-regulated in the C1/N and C2/N groups were predominantly involved in functions such as amino acid binding, binding of phosphorylated compounds, and serine protease activity. Notably, proteins like NADH dehydrogenase, ATP synthase, oxidoreductases, and iron ion channels were significantly elevated in the C1 versus C2 comparative group. Through meticulous analysis of differential expression multiples, statistical significance, and involvement in metabolic pathways, this study identified eight potential biomarkers pertinent to PTC metastasis diagnostics, encompassing phosphorylated myosin 10, phosphorylated proline-directed protein kinase, leucine tRNA synthetase, 2-oxo-isovalerate dehydrogenase, succinic semialdehyde dehydrogenase, ADP/ATPtranslocase, pyruvate carboxylase, and fibrinogen. Therapeutic assays employing metformin, an AMP-activated protein kinase (AMPK) activator, alongside the phosphorylation-specific inhibitor ML-7 targeting Myosin10, demonstrated attenuated cellular proliferation, migration, and invasion capabilities in thyroid cancer cells, accompanied by a reduction in amino acid pools. Cellular colocalization and interaction studies elucidated that AMPK activation imposes an inhibitory influence on Myosin10 levels. The findings of this research corroborate the utility of proteomic and phosphoproteomic platforms in the identification of metastatic markers for PTC and suggest that modulation of AMPK activity, coupled with the inhibition of Myosin10 phosphorylation, may forge novel therapeutic avenues in the management of thyroid carcinoma. SIGNIFICANCE: The significance of our research lies in its potential to transform the current understanding and management of thyroid papillary carcinoma (PTC), particularly in its metastatic form. By integrating both proteomic and phosphoproteomic analyses, our study not only sheds light on the molecular alterations associated with PTC but also identifies eight novel biomarkers that could serve as indicators of metastatic potential.

Tension Induced Photoluminescence Enhancement in an Organic Single Crystal.

Organic single crystals possess distinct advantages due to their highly ordered molecular structures, resulting in improved stability, enhanced carrier mobility, and superior optical characteristics. However, their mechanical rigidity and brittleness impede the applications in flexible and wearable optoelectronic devices. Here, photoluminescence (PL) emission from 2,6-diphenylanthracene (DPA) single crystals is studied under tensile strain, which shows PL enhancement by more than two times with a strain of ≈1.42%. Such a tension induced PL enhancement is reversible, exhibiting no clear optical degradations during 100 cycles of bending and recovery processes. Theoretical calculations reveal that the deformation of molecular structure under strain induces a decrease of the dihedral between anthracene and benzene moieties in DPA molecules. Further, the increased molecular conjugation enhances the molecular oscillator strength, leading to the brightened PL emission. Meanwhile, with the decreased dihedral, the molecular vibrations in DPA crystals are suppressed, which can reduce the non-radiative decay rate. In contrast, no tension induced PL enhancement is observed in polycrystalline DPA thin films as the strain can be released via the grain boundaries. This study highlights the superior optical performance of DPA single crystals under strain field, which will provide new possibilities for DPA-based flexible devices.

Efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor for lung adenosquamous cell carcinoma harboring EGFR mutation: a retrospective study and pooled analysis.

Objectives: To explore the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) on lung adenosquamous cell carcinoma (ASC) with EGFR mutation. Methods: Efficacy of EGFR-TKIs in the treatment of advanced or recurrent lung ASC with EGFR mutations was assessed retrospectively in 44 patients. Pooled analysis of 74 patients using EGFR-TKIs, including 30 patients selected from 11 publications, was conducted. Results: In our retrospective research, patients treated with EGFR-TKI in ASC with EGFR mutations had objective response rate (ORR) of 54.5%, disease control rate (DCR) of 79.5%, median progression free survival (mPFS) of 8.8 months, and median overall survival (mOS) of 19.43 months, respectively. A pooled analysis reveals ORR, DCR, mPFS, and mOS are, respectively, 63.4%, 85.9%, 10.00 months, and 21.37 months for ASC patients. In patients with deletions in exon 19 and exon 21 L858R mutations, mPFS (11.0 versus 10.0 months, P=0.771) and mOS (23.67 versus 20.33 months, P=0.973) were similar. Erlotinib or gefitinib-treated patients had an overall survival trend that was superior to that of icotinib-treated patients. Conclusions: ASC harboring EGFR mutations can be treated with EGFR-TKI in a similar manner to Adenocarcinoma (ADC) harboring EGFR mutations. There is still a need for further investigation to identify the separate roles of ASC's two components in treating EGFR.

A novel causative factor of injury: Severe burns related to fires and explosions of lithium-ion batteries of electric motorcycles.

Severe burns related to fires and explosions of lithium-ion batteries of electric motorcycles have not been reported to date. We retrospectively studied 419 patients admitted to our burn intensive care unit from January 2016 to December 2021. Of these 419 patients, 26 (22 male, 4 female; median age, 42 years) had burns related to lithium-ion battery fires and explosions, and all of their injury characteristics were similar to those of traditional flame burns. Lithium-ion battery-related burns were the eighth most common cause of burn injuries among all hospitalized patients. The 26 patients comprised 10 unemployed and 16 employed individuals. Twenty-three patients were injured at home during the battery charging process, and three were injured outdoors (one by a fire while the electric motorcycle was stationary and the others two by a fire while riding the motorcycle). The burn sites were distributed over the whole body; the burn area ranged from 10 % to 100 % of the total body surface area, and the burn depth ranged from superficial second-degree burns to third-degree burns. Twenty-three patients had inhalation injuries, and ten underwent prophylactic tracheostomy and intubation. Multiple operations were required for wound repair. Although convenient, lithium-ion electric motorcycles can also cause severe burns. To prevent these injuries, we must increase public safety awareness and education, develop new battery energy storage systems and battery management systems, and ensure the safety of batteries. Consumers should be aware of the potential dangers of lithium-ion batteries and comply with related security measures.

Plasma-assisted synthesis of ultra-fine NiCo2O4/NiCo-layered double hydroxides nanoparticles-decorated electrospun carbon nanofibers with enhanced electrochemical performance.

Nickel cobaltate/NiCo-layered double hydroxides (NiCo2O4/NiCo-LDH) as energy storage materials offer considerable potential for various applications. However, many of current methods for synthesizing NiCo2O4/NiCo-LDH suffer from long synthesis times, complex preparation process, and high temperatures and high pressures. In this study, we present a green, simple, and efficient approach known as assisted liquid-phase plasma electrolysis, which realizes the rapid fabrication of ultra-fine NiCo2O4/NiCo-LDH nanoparticle-decorated electrospun carbon nanofibers (NiCo2O4/NiCo-LDH/CNFs) composites. Ultra-fine NiCo2O4/NiCo-LDH nanoparticles (<70 nm) are uniformly deposited on the CNF surface. The CNFs are intertwined to form a highly conductive three-dimensional mesh structure, which synergizes the NiCo2O4/NiCo-LDH nanoparticles with a high specific capacitance in favor of ion/electron transport efficiency. In addition, the cooperative effect between the two phases of NiCo2O4 and NiCo-LDH further improves the electrochemical properties. The NiCo2O4/NiCo-LDH/CNFs composites exhibit a high specific capacitance of 1534.7 F/g at 1 A/g and a capacitance retention of 93.9 % after 5000 cycles. An assembled asymmetric supercapacitor using activated carbon and NiCo2O4/NiCo-LDH/CNFs composites achieves an energy density of 33.8 Wh/kg at a power density of 400 W/kg and a capacitance retention of 93.0 % after 5000 cycles. Notably, two series-connected NiCo2O4/NiCo-LDH/CNFs ASC supercapacitors can light up an LED bulb, which maintains a certain brightness even after 50 min. Hence, this work provides a new and efficient route for synthesizing carbon-based NiCo2O4/NiCo-LDH composites for use as advanced energy storage materials.

A highly sensitive and colorimetric fluorescent probe for visualizing hydroxylamine in immune cells.

BACKGROUND: Hydroxylamine (HA) is vital industrial raw material and pharmaceutical intermediate. In addition, HA is an important cellular metabolite, which is intermediate in the formation of nitric oxide and nitroxide. However, excessive amounts of HA are toxic to both animals and plants. Conventional methods for the detection of HA are cumbersome and complicated. The detection of HA with fluorescent probes is convenient and sensitive. There are few probes available for the detection of hydroxylamine. Therefore, a fluorescent probe for the sensitive and selective detection of HA was developed in this work. RESULTS: A coumarin derivative SWJT-22 was synthesized as a colorimetric fluorescent probe to detect hydroxylamine (HA), with high sensitivity and selectivity. The detection limit of the probe to HA was 0.15 µM, which was lower than most probes of HA. Upon the addition of HA to aqueous solution containing SWJT-22, the color of the solution changed from orange to yellow, and the fluorescence color also changed from orange to green. The reaction mechanism of SWJT-22 to HA was confirmed by 1H NMR titrations, mass spectrometry and round bottom flask experiments. Moreover, SWJT-22 had been fabricated into portable test strips for the detection of HA. SWJT-22 had been successfully used in cellular imaging and could detect both endogenous and exogenous HA in HeLa cells and RAW 264.7 cells. SIGNIFICANCE: Due to the physiological role of hydroxylamine in organisms, it is crucial to detect hydroxylamine selectively and sensitively. This work provided a convenient tool for the detection of hydroxylamine, not only to detect endogenous and exogenous HA in cells, but also made into portable test strips. The HA fluorescent probe SWJT-22 is expected to promote the study of HA in physiological processes.

Development of a Zr-Based Metal-Organic Framework (UiO-66) for a Cooperative Flame Retardant in the PC/ABS.

Polycarbonate/acrylonitrile butadiene styrene (PC/ABS) blends are widely used as engineering plastic alloys; however, they have a low fire safety level. To improve the flame-retardant property of PC/ABS, a zirconium-based metal-organic framework material (UiO-66) was synthesized with zirconium chloride and terephthalic acid and used as a flame-retardant cooperative agent. Its flame-retardant performance and mode of action in the PC/ABS blends were carefully investigated. The results showed that UiO-66 had good thermal stability and delayed the pyrolysis of the materials, thus significantly enhancing the efficiency of intumescent flame retardants. By compounding 7.0 wt% hexaphenyloxy-cyclotri-phosphazene (HPCTP) with 3.0 wt% UiO-66, the PC/ABS blends reached a limiting oxygen index value of 27.0% and V0 rating in the UL-94 test, showing significantly improved resistance to combustion dripping. In addition, UiO-66 enhanced the smoke and heat suppression characteristics of the intumescent flame-retardant materials. Finally, the flame-retardant mode of action in the blends was indicative of UiO-66 having a cooperative effect on the flame-retardant performance of PC/ABS/HPCTP materials. This work provides good ideas for further development of the flame-retardant ABS/PC.

Drug-Target Interaction Prediction Based on an Interactive Inference Network.

Drug-target interactions underlie the actions of chemical substances in medicine. Moreover, drug repurposing can expand use profiles while reducing costs and development time by exploiting potential multi-functional pharmacological properties based upon additional target interactions. Nonetheless, drug repurposing relies on the accurate identification and validation of drug-target interactions (DTIs). In this study, a novel drug-target interaction prediction model was developed. The model, based on an interactive inference network, contains embedding, encoding, interaction, feature extraction, and output layers. In addition, this study used Morgan and PubChem molecular fingerprints as additional information for drug encoding. The interaction layer in our model simulates the drug-target interaction process, which assists in understanding the interaction by representing the interaction space. Our method achieves high levels of predictive performance, as well as interpretability of drug-target interactions. Additionally, we predicted and validated 22 Alzheimer's disease-related targets, suggesting our model is robust and effective and thus may be beneficial for drug repurposing.

Two rhombic ice phases from aqueous salt solutions under graphene confinement.

Water exhibits rich ice phases depending upon its respective formation conditions, and in particular, the two-dimensional ice with nonhexagonal symmetry adsorbed on solids relates to the exceptional arrangement of water molecules. Despite extensive reporting of two-dimensional ice on various solid surfaces, the geometry and thermodynamics of ice formation from an aqueous salt solution are still unknown. In this Letter, we show the formation of single- and two-phase mixed two-dimensional rhombic ice from aqueous salt solutions with different concentrations under strong compressed confinement of graphene at ambient temperature by using classical molecular dynamics simulations and first-principles calculations. The two rhombic ice phases exhibit identical geometry and thermodynamic properties, but different projections of the oxygen atoms against solid surface symmetry, where they relate to the stable and metastable arrangements of water molecules confined between two graphene layers. A single-phase rhombic ice would grow from the confined saturated aqueous solutions since the previously stable rhombic molecular arrangement becomes an unstable high-energy state by introducing salt ions nearby. Our result reveals different rhombic ice phases growing from pure water and aqueous solutions, highlighting the deciding role of salt ions in the ice formation process due to their common presence in liquids.

Risk factors and prediction model for mortality in HIV/Talaromyces marneffei co-infection: A retrospective cohort study.

Background: This study aimed to identify the risk factors associated with mortality among patients co-infected with human immunodeficiency virus (HIV) and Talaromyces marneffei (TM) in China, and develop a risk prediction model. Methods: In this retrospective cohort analysis conducted from 2013 to 2024, comprehensive clinical data from 160 patients were analyzed using a logistic regression model to identify mortality predictors and construct a predictive model. An additional 36 patients constituted the validation cohort, which was specifically designed to evaluate the predictive value of the model. Model performance was assessed using the area under the curve (AUC). Results: The overall mortality rate for hospitalized patients with HIV/TM co-infection was 17.35 %. The median age was 35.0 years, and 89.30 % were male. Additionally, 89.80 % of the patients reported fever and 87.76 % presented with lymphadenopathy. Key independent risk factors associated with mortality included age (odds ratio (OR): 1.103, 95 % confidence interval (CI) = 1.033-1.178, P = 0.003), procalcitonin (PCT) levels (OR: 1.270, 95 % CI = 1.052-1.534, P = 0.013), and urea to albumin ratio (UAR) (OR: 1.491, 95 % CI = 1.175-1.892, P < 0.001). Advanced age, elevated PCT levels, and increased UAR were identified as independent risk factors of mortality. Furthermore, the mortality prediction probability combining age, PCT, and UAR exhibited a high predictive value in patients with HIV/TM co-infection. Additionally, the AUC showed a good discrimination ability in the validation group (AUC, 0.898). Conclusions: Advanced age, elevated PCT levels, and increased UAR significantly determine mortality in patients with HIV/TM co-infection. These findings underscore the potential of using laboratory parameters as predictive indicators of mortality, facilitating the early identification of HIV/TM co-infection cases in clinical practice.