Search

Drug-induced liver injury caused acute hepatic failure and hepatitis frequently. In this investigation, kakuol and asarinin reduced the levels of serum alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) dramatically, and ameliorated the pathological damage of liver tissues in APAP-induced mice. Furthermore, both compounds increased the viabilities of APAP-induced L-O2 cells and extracellular glutathione (GSH) levels accompanied significantly by reducing the level of intracellular ROS in vitro. In addition, HSP90AA1/CDK2/mTOR signaling pathway and five target proteins (CDK2, HSP90AA1, HRAS, MMP1, mTOR) were proposed from network pharmacology and molecular docking prediction, and then the up-regulation of protein expression of CDK2, mTOR and down-regulation of HSP90AA1, HRAS, MMP1 by kakuol and asarinin in western blotting supported their mechanism., (Copyright © 2024. Published by Elsevier B.V.)

Quasi-solid-state aqueous zinc ion batteries suffer from anodic zinc dendrite growth during plating/stripping processes, impeding their commercial application. The inhibition of zinc dendrites by high-modulus electrolytes has been proven to be effective. However, hydrogel electrolytes are difficult to achieve high modulus owing to their inherent high water contents. This work reports a hydrogel electrolyte with ultrahigh modulus that can overcome the growth stress of zinc dendrites through mechanical suppression effect. By combining wet-annealing, solvent-exchange, and salting-out processes and tuning the hydrophobic and crystalline domains, a hydrogel electrolyte is obtained with substantial water content (≈70%), high modulus (198.5 MPa), high toughness (274.3 MJ m -3 ), and high zinc-ion conductivity (28.9 mS cm -1 ), which significantly outperforms the previously reported poly(vinyl alcohol)-based hydrogels. As a result, the hydrogel electrolyte exhibits excellent dendrite-suppression effect and achieves stable performance in Zn||Zn symmetric batteries (1800 h of cycle life at 1 mA cm -2 ). Moreover, the Zn||V 2 O 5 pouch batteries display excellent cycling life and operate stably even under extreme conditions, such as large bending angle (180°) and automotive crushing. This work provides a promising approach for designing mechanically reliable hydrogel electrolytes for advanced aqueous zinc ion batteries., (© 2024 Wiley‐VCH GmbH.)

The abuse of antibiotics leads to the rapid spread of bacterial resistance, which seriously threatens human life and health. Now, 8 resorcylic acid derivatives, including 4 new compounds (1-4) were isolated from Lysimachia tengyuehensis by bio-guided isolation, and they inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (MIC = 4-8 μg/mL). Notably, 1 and 2 rapidly killed MRSA and VRE within 40 min without drug resistance in 20 days. Mechanically, they potently disrupted biofilm and cell membrane by interfering with bacterial metabolic imbalance. The structure-activity relationship (SAR) revealed that the lipophilic long carbon chains (C-5/C-6) and hydrophilic hydroxyl/carboxyl groups were essential for the anti-MRSA and VRE bioactivity. Additionally, they effectively recovered MRSA-infected skin wounds and VRE-infected peritoneal in vivo. Resorcylic acid derivatives showed significant anti-MRSA and VRE bioactivity in vitro and in vivo with potential application for the first time., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Reducing exposure to risk factors and screening represent 2 major approaches to gastric cancer (GC) prevention, but public knowledge GC risk factors and screening behaviour remain unknown. We aimed to investigate public awareness of GC risk factors, adherence to screening, and barriers hindering screening practices in China., Methods: This community-based household survey was conducted within Shijiazhuang, China, and 1490 residents were recruited through a multistage stratified cluster random sampling approach. A self-administered questionnaire was completed which consisted of three sections: demographics, awareness of GC risk factors, and personal screening behaviours. Factors associated with knowledge of risk factors and screening behaviours were evaluated using binary logistic regression analysis., Results: The mean risk factor awareness score of 12 (7, 15) revealed insufficient knowledge in 51.1% of participants. Dietary lifestyle factors were better understood than physical activity and weight-related factors. Marital status (OR 1.967; 95% CI 1.415 to 2.734), higher income (OR 1.197; 95% CI 1.010 to 1.418), and a history of upper gastrointestinal problems (OR 0.048; 95% CI 1.002 to 1.311) were associated with higher awareness. Merely 21.5% underwent GC screening, with higher rates linked to older age (OR 1.642; 95% CI 1.418 to 1.902), higher education (OR 1.398; 95% CI 1.176 to 1.662), a history of upper gastrointestinal problems (OR 3.842; 95% CI 2.833 to 5.209), and moderate (OR 2.077; 95% CI 1.352 to 3.191) and high (OR 2.529; 95% CI 1.311 to 4.878) perceived GC risk. Notably, participants commonly refused gastroscopy due to the absence of symptoms or signs., Conclusions: In Shijiazhuang, more than half of participants demonstrated inadequate knowledge of GC risk factors, and screening participation rates were remarkably low. This emphasizes the need for targeted interventions to enhance GC awareness and significantly improve screening rates., Competing Interests: The authors have declared that no competing interest exsist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To analyze the association between the hemoglobin glycation index (HGI) and the long-term prognosis of patients with coronary artery disease (CAD)., Methods: HGI represented the difference between laboratory measured Hemoglobin A1c (HbA1c) and predicted HbA1c based on a liner regression between Hb1Ac and fasting plasma glucose (FPG). A total of 10 598 patients who treated with percutaneous coronary intervention (PCI) were stratified into three groups (low HGI group: HGI<-0.506, medium HGI group: -0.506 ≤ HGI < 0.179, and high HGI group: HGI ≥ 0.179). The primary endpoints includes all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs)., Results: A total of 321 ACMs, 243 CMs, 774 MACEs, and 854 MACCEs were recorded during a 60-month follow-up period. After adjusting for confounders using a multivariate Cox regression analysis, the patients in the low HGI group had a significantly increased risk of ACM (adjusted HR = 1.683, 95%CI:1.179-2.404, P = 0.004) and CM (HR = 1.604, 95%CI:1.064-2.417, P = 0.024) as compared with patients in the medium HGI group. Similarly, the patients in the high HGI group had an increased risk of MACEs (HR = 1.247, 95% CI: 1.023-1.521, P = 0.029) as compared with patients in the medium HGI group. For ACM, CM, and MACEs, a U-shaped relation were found among these three groups. However, we did not find significant differences in the incidence of MACCEs among these three groups., Conclusion: The present study indicates that HGI could be an independent predictor for the risk of mortality and MACEs in patients with CAD., (© 2024. The Author(s).)

Objective: To investigate the impact of comprehensive health education on insulin therapy outcomes in diabetic patients., Methods: A total of 130 diabetes mellitus patients admitted to our hospital between January 2020 and January 2023 were enrolled. We used a randomization method to divide participants into two groups, one of which received the "admission-discharge-home follow-up" comprehensive health education program and the other which did not. They were randomly divided into an observation group and a control group (65 patients in each). The control group received conventional education, while the observation group received additional one-stop health education involving "admission-discharge-family follow-up." Various parameters, including 2-hour postprandial blood glucose (2hPG), fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), insulin injection compliance, insulin standard injection mastery, and quality of life (assessed using the Insulin Therapy Related Quality of Life Questionnaire, ITR-QOL-CV), were compared between the two groups., Results: The study's key findings highlight the significant effects of a comprehensive health education program on key outcomes such as improving insulin injection compliance, improving glycemic control, and improving quality of life in patients with diabetes. Before the intervention, 2hPG, FPG, and HbA1c levels were similar in both groups (P > .05). Following the intervention, these indicators decreased in both groups, with significantly lower levels observed in the observation group (P < .05). Insulin injection compliance was comparable between the groups before the intervention (P > .05), but it increased in both groups post-intervention, with higher compliance observed in the observation group (P < .05). Similarly, scores from the insulin standard injection mastery questionnaire and ITR-QOL-CV were enhanced in both groups after the intervention, with higher scores in the observation group compared to the control group (P < .05)., Conclusion: The implementation of one-stop health education involving "admission-discharge-family follow-up" led to improved insulin injection effectiveness, blood glucose control, compliance, insulin standard injection mastery, and overall quality of life in diabetic patients. These significant improvements have important clinical implications for patients with diabetes, as more efficient and consistent use of insulin injections will help to better control blood sugar levels, reducing patients' symptoms and risk of complications. For health care providers, these findings underscore the importance of providing comprehensive health education programs to improve outcomes and overall care for patients with diabetes.

Nickel/photoredox catalysis has emerged as a powerful platform for exploring nontraditional and challenging cross-couplings. Herein, a metallaphotoredox catalytic protocol has been developed on the basis of a tertiary amine-ligated boryl radical-induced halogen atom transfer process under blue-light irradiation. A wide variety of aryl and heteroaryl bromides featuring different functional groups and pharmaceutical moieties were facilely coupled to rapidly install C(sp 3 )-enriched aromatic scaffolds. The compatibility of Lewis base-ligated borane with nickel catalysis was well exemplified to extend the chemical space for Ni-catalyzed cross-electrophile coupling.

Two new abietane diterpenoids, cartrisine A (1) and cartrisine B (2) were isolated from Caryopteris trichosphaera. Their structures were elucidated based on HR-ESI-MS and NMR spectral data. Compound 2 exhibited moderate antibacterial bioactivity against MRSA and VRE, and showed a strong synergistic effect with market antibiotics against MRSA and VRE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Wernicke encephalopathy is a neurological disorder caused by thiamine deficiency, commonly seen in alcoholic populations but also involving other circumstances that may lead to thiamine deficiency. The recognition of Wernicke encephalopathy often depends on clinicians' keen ability to detect its typical triad of features; however, most cases do not present with the full constellation of signs, which complicates the timely identification of Wernicke encephalopathy., Case Summary: This case report describes a patient with nasopharyngeal carcinoma who developed abnormal ocular function and ataxia following concurrent chemoradiotherapy, without a history of alcohol abuse. With the aid of radiological examinations, he received a timely diagnosis and treatment; however, his symptoms did not fully resolve during follow-up., Conclusion: For patients with malignant tumors exhibiting neurological symptoms, clinicians should consider the possibility of Wernicke encephalopathy and provide prophylactic thiamine therapy., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Herein, visible light-induced, nickel-catalyzed direct functionalization of the Hantzsch esters (HEs) with readily accessible alkyl bromides has been successfully achieved by taking advantage of HE as the reductant and substrate through an aromatization-dearomatization process. In this strategy, the single electron reduction of alkyl bromides by reactive Ni(I) species is essential for the success of this late-stage transformation. A wide range of 4-alkyl-1,4-dihydropyridines were rapidly assembled in moderate to good yields under mild conditions, rendering this photoinduced approach attractive for synthetic and medicinal chemistry.

Previous studies of hematopoietic stem cells (HSCs) primarily focused on single cell-based niche models, yielding fruitful but conflicting findings 1-5 . Here we report our investigation on the fetal liver (FL) as the primary fetal hematopoietic site using spatial transcriptomics. Our study reveals two distinct niches: the portal-vessel (PV) niche and the sinusoidal niche. The PV niche, composing N-cadherin (N-cad) Hi Pdgfrα + mesenchymal stromal cells (MSCs), endothelial cells (ECs), and N-cad Lo Albumin + hepatoblasts, maintains quiescent and multipotential FL-HSCs. Conversely, the sinusoidal niche, comprising ECs, hepatoblasts and hepatocytes, as well as potential macrophages and megakaryocytes, supports proliferative FL-HSCs biased towards myeloid lineages. Unlike prior reports on the role of Cxcl12, with its depletion from vessel-associated stromal cells leading to 80% of HSCs' reduction in the adult bone marrow (BM) 6,7 , depletion of Cxcl12 via Cdh2 CreERT (encoding N-cad) induces altered localization of HSCs from the PV to the sinusoidal niches, resulting in an increase of HSC number but with myeloid-bias. Similarly, we discovered that adult BM encompasses two niches within different zones, each composed of multi-cellular components: trabecular bone area (TBA, or metaphysis) supporting deep-quiescent HSCs, and central marrow (CM, or diaphysis) fostering heterogenous proliferative HSCs. This study transforms our understanding of niches by shifting from single cell-based to multicellular components within distinct zones, illuminating the intricate regulation of HSCs tailored to their different cycling states.

Ethnopharmacological Relevance: Corydalis decumbens (Thunb.) Pers. was used as stasis-eliminating medicine traditionally to treat cardiovascular disease potentially attributed to its antithrombotic effect, but lack of pharmacological research on it., Aim of the Study: To investigate the antithrombotic effect of C. decumbens and its preliminary mechanism., Materials and Methods: A carrageenan-induced mouse thrombus model and adenosine diphosphate stimulated platelet aggregation of rabbits were used to confirm the inhibitory effect of C. decumbens extract and compounds on thrombosis in vivo. Then, H 2 O 2 -induced human umbilical vein endothelial cells (HUVECs) injury model was further adopted to verify the effects of bioactive compounds in vitro. Moreover, in silico network pharmacology analyses and molecular docking were performed to predict the underlying mechanisms, targets, and pathways, and which were further confirmed through western blotting assay., Results: The administration of total extract (TE), total alkaloids (TA) and tetrahydropalmatine (TET) resulted in a significant reduction in black tail thrombus and congestion, along with a decreasing in platelet aggregation of rabbits. A superior antithrombotic effect indicated the bioactive fraction, and then the isolated bioactive compounds, TET and protopine (PRO) increased cell survival, and decreased reactive oxygen species (ROS) and lactate dehydrogenase (LDH) release in H 2 O 2 -induced HUVECs injury model. Moreover, the two alkaloids targeted 33 major proteins and influenced 153 pathways in network pharmacology prediction. Among these, HSP90AA1, COX-2, NF-κB/p65, MMP1 and HIF-1α were the key proteins and PI3K-Akt emerged as the major signaling pathway. Further western blotting results supported that five key proteins were downregulated by the two bioactive compounds in H 2 O 2 -stimulated HUVECs model., Conclusion: C. decumbens exerted protective effect on thrombosis through inhibiting PI3K-Akt pathway and related key proteins, which supported the traditional use and presented potential antithrombotic alkaloids for further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Isoprene affects new particle formation rates in environments and experiments also containing monoterpenes. For the most part, isoprene reduces particle formation rates, but the reason is debated. It is proposed that due to its fast reaction with OH, isoprene may compete with larger monoterpenes for oxidants. However, by forming a large amount of peroxy-radicals (RO 2 ), isoprene may also interfere with the formation of the nucleating species compared to a purely monoterpene system. We explore the RO 2 cross reactions between monoterpene and isoprene oxidation products using the radical Volatility Basis Set (radical-VBS), a simplified reaction mechanism, comparing with observations from the CLOUD experiment at CERN. We find that isoprene interferes with covalently bound C 20 dimers formed in the pure monoterpene system and consequently reduces the yields of the lowest volatility (Ultra Low Volatility Organic Carbon, ULVOC) VBS products. This in turn reduces nucleation rates, while having less of an effect on subsequent growth rates., Competing Interests: The authors declare no conflicts., (This journal is © The Royal Society of Chemistry.)

Introduction: Allergic rhinitis (AR) is a respiratory immune system disorder characterized by dysregulation of immune responses. Within the context of AR, gut microbiota and its metabolites have been identified as contributors to immune modulation. These microorganisms intricately connect the respiratory and gut immune systems, forming what is commonly referred to as the gut-lung axis. Xiaoqinglong Decoction (XQLD), a traditional Chinese herbal remedy, is widely utilized in traditional Chinese medicine for the clinical treatment of AR. In this study, it is hypothesized that the restoration of symbiotic microbiota balance within the gut-lung axis plays a pivotal role in supporting the superior long-term efficacy of XQLD in AR therapy. Therefore, the primary objective of this research is to investigate the impact of XQLD on the composition and functionality of the gut microbiota in a murine model of AR., Methods: An ovalbumin-sensitized mouse model to simulate AR was utilized, the improvement of AR symptoms after medication was investigated, and high-throughput sequencing was employed to analyze the gut microbiota composition., Results: XQLD exhibited substantial therapeutic effects in AR mice, notably characterized by a significant reduction in allergic inflammatory responses, considerable alleviation of nasal symptoms, and the restoration of normal nasal function. Additionally, following XQLD treatment, the disrupted gut microbiota in AR mice displayed a tendency toward restoration, showing significant differences compared to the Western medicine (loratadine) group., Discussion: This results revealed that XQLD may enhance AR allergic inflammatory responses through the regulation of intestinal microbiota dysbiosis in mice, thus influencing the dynamics of the gut-lung axis. The proposal of this mechanism provides a foundation for future research in this area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Chen, Yun-Dang, Yan, He, Li, Ruan and Wu.)

Iodine oxoacids are recognised for their significant contribution to the formation of new particles in marine and polar atmospheres. Nevertheless, to incorporate the iodine oxoacid nucleation mechanism into global simulations, it is essential to comprehend how this mechanism varies under various atmospheric conditions. In this study, we combined measurements from the CLOUD (Cosmic Leaving OUtdoor Droplets) chamber at CERN and simulations with a kinetic model to investigate the impact of temperature, ionisation, and humidity on iodine oxoacid nucleation. Our findings reveal that ion-induced particle formation rates remain largely unaffected by changes in temperature. However, neutral particle formation rates experience a significant increase when the temperature drops from +10 °C to -10 °C. Running the kinetic model with varying ionisation rates demonstrates that the particle formation rate only increases with a higher ionisation rate when the iodic acid concentration exceeds 1.5 × 10 7 cm -3 , a concentration rarely reached in pristine marine atmospheres. Consequently, our simulations suggest that, despite higher ionisation rates, the charged cluster nucleation pathway of iodic acid is unlikely to be enhanced in the upper troposphere by higher ionisation rates. Instead, the neutral nucleation channel is likely to be the dominant channel in that region. Notably, the iodine oxoacid nucleation mechanism remains unaffected by changes in relative humidity from 2% to 80%. However, under unrealistically dry conditions (below 0.008% RH at +10 °C), iodine oxides (I 2 O 4 and I 2 O 5 ) significantly enhance formation rates. Therefore, we conclude that iodine oxoacid nucleation is the dominant nucleation mechanism for iodine nucleation in the marine and polar boundary layer atmosphere., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Herein, a dual photoredox/nickel catalyzed formylation of aryl bromide with commercially available 2,2-dimethoxy- N , N -dimethylethan-1-amine as an effective CO source has been successfully achieved, delivering a series of aromatic aldehydes in moderate to good yields. Compared with the traditional reductive carbonylation process, this newly designed synthetic protocol provides a straightforward toolbox to access aromatic aldehydes, obviating the use of carbon monoxide and stoichiometric reductants. Finally, the utility of this direct formylation reaction was demonstrated in the pharmaceutical analogue synthesis.

Hematopoietic stem cells (HSCs) rely on specialized microenvironments known as niches to maintain their self-renewal and multilineage potential to generate diverse types of blood cells continuously. Over the last two decades, substantial advancements have been made in unraveling the niche cell components and HSC localizations under homeostatic and stressed circumstances. Advances in imaging, combined with the discovery of phenotypic surface markers combinations and single cell sequencing, have greatly facilitated the systematic examination of HSC localizations. This review aims to present a summary of HSC localizations, highlighting potential distinctions between phenotypically and functionally defined HSCs, and explore the functionality of niches in ensuring the integrity and long-term maintenance of HSCs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aerosols formed and grown by gas-to-particle processes are a major contributor to smog and haze in megacities, despite the competition between growth and loss rates. Rapid growth rates from ammonium nitrate formation have the potential to sustain particle number in typical urban polluted conditions. This process requires supersaturation of gas-phase ammonia and nitric acid with respect to ammonium nitrate saturation ratios. Urban environments are inhomogeneous. In the troposphere, vertical mixing is fast, and aerosols may experience rapidly changing temperatures. In areas close to sources of pollution, gas-phase concentrations can also be highly variable. In this work we present results from nucleation experiments at -10 °C and 5 °C in the CLOUD chamber at CERN. We verify, using a kinetic model, how long supersaturation is likely to be sustained under urban conditions with temperature and concentration inhomogeneities, and the impact it may have on the particle size distribution. We show that rapid and strong temperature changes of 1 °C min -1 are needed to cause rapid growth of nanoparticles through ammonium nitrate formation. Furthermore, inhomogeneous emissions of ammonia in cities may also cause rapid growth of particles., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Highly oxygenated organic molecules (HOMs) are a major source of new particles that affect the Earth's climate. HOM production from the oxidation of volatile organic compounds (VOCs) occurs during both the day and night and can lead to new particle formation (NPF). However, NPF involving organic vapors has been reported much more often during the daytime than during nighttime. Here, we show that the nitrate radicals (NO 3 ), which arise predominantly at night, inhibit NPF during the oxidation of monoterpenes based on three lines of observational evidence: NPF experiments in the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN (European Organization for Nuclear Research), radical chemistry experiments using an oxidation flow reactor, and field observations in a wetland that occasionally exhibits nocturnal NPF. Nitrooxy-peroxy radicals formed from NO 3 chemistry suppress the production of ultralow-volatility organic compounds (ULVOCs) responsible for biogenic NPF, which are covalently bound peroxy radical (RO 2 ) dimer association products. The ULVOC yield of α-pinene in the presence of NO 3 is one-fifth of that resulting from ozone chemistry alone. Even trace amounts of NO 3 radicals, at sub-parts per trillion level, suppress the NPF rate by a factor of 4. Ambient observations further confirm that when NO 3 chemistry is involved, monoterpene NPF is completely turned off. Our results explain the frequent absence of nocturnal biogenic NPF in monoterpene (α-pinene)-rich environments.

Iodine oxoacids (HIO 3 and HIO 2 )-driven nucleation has been suggested to efficiently contribute to new particle formation (NPF) in marine atmospheres. Abundant atmospheric nucleation precursors may further enhance HIO 3 -HIO 2 -driven nucleation through various multicomponent nucleation mechanisms. However, the specific enhancing potential (EP) of different precursors remains largely unknown. Herein, the EP-based screening model of precursors and enhancing mechanism of the precursor with the highest EP on HIO 3 -HIO 2 nucleation were investigated. The formation free energies (Δ G ), as critical parameters for evaluating EP, were calculated for the dimers of 63 selected precursors with HIO 2 . Based on the Δ G values, (1) a quantitative structure-activity relationship model was developed for evaluating Δ G of other precursors and (2) atmospheric concentrations of 63 (precursor) 1 (HIO 2 ) 1 dimer clusters were assessed to identify the precursors with the highest EP for HIO 3 -HIO 2 -driven nucleation by combining with earlier results for the nucleation with HIO 3 as the partner. Methanesulfonic acid (MSA) was found to be one of the precursors with the highest EP. Finally, we found that MSA can effectively enhance HIO 3 -HIO 2 nucleation at atmospheric conditions by studying larger MSA-HIO 3 -HIO 2 clusters. These results augment our current understanding of HIO 3 -HIO 2 and MSA-driven nucleation and may suggest a larger impact of HIO 2 in atmospheric aerosol nucleation.

During summer, ammonia emissions in Southeast Asia influence air pollution and cloud formation. Convective transport by the South Asian monsoon carries these pollutant air masses into the upper troposphere and lower stratosphere (UTLS), where they accumulate under anticyclonic flow conditions. This air mass accumulation is thought to contribute to particle formation and the development of the Asian Tropopause Aerosol Layer (ATAL). Despite the known influence of ammonia and particulate ammonium on air pollution, a comprehensive understanding of the ATAL is lacking. In this modelling study, the influence of ammonia on particle formation is assessed with emphasis on the ATAL. We use the EMAC chemistry-climate model, incorporating new particle formation parameterisations derived from experiments at the CERN CLOUD chamber. Our diurnal cycle analysis confirms that new particle formation mainly occurs during daylight, with a 10-fold enhancement in rate. This increase is prominent in the South Asian monsoon UTLS, where deep convection introduces high ammonia levels from the boundary layer, compared to a baseline scenario without ammonia. Our model simulations reveal that this ammonia-driven particle formation and growth contributes to an increase of up to 80% in cloud condensation nuclei (CCN) concentrations at cloud-forming heights in the South Asian monsoon region. We find that ammonia profoundly influences the aerosol mass and composition in the ATAL through particle growth, as indicated by an order of magnitude increase in nitrate levels linked to ammonia emissions. However, the effect of ammonia-driven new particle formation on aerosol mass in the ATAL is relatively small. Ammonia emissions enhance the regional aerosol optical depth (AOD) for shortwave solar radiation by up to 70%. We conclude that ammonia has a pronounced effect on the ATAL development, composition, the regional AOD, and CCN concentrations., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Herein, a visible-light-induced nickel-catalyzed cross-coupling of aryl bromide with nitrile has been reported. By utilization of readily available nitriles as carbonyl precursors, a range of structurally diverse aryl ketones were facilely constructed. The synthetic simplicity, mild reaction conditions, and acidic functional group tolerance would broaden the synthetic utilities of this developed protocol as an expedient alternative to Grignard/organolithium protocols.

The main nucleating vapor in the atmosphere is thought to be sulfuric acid (H 2 SO 4 ), stabilized by ammonia (NH 3 ). However, in marine and polar regions, NH 3 is generally low, and H 2 SO 4 is frequently found together with iodine oxoacids [HIO x , i.e., iodic acid (HIO 3 ) and iodous acid (HIO 2 )]. In experiments performed with the CERN CLOUD (Cosmics Leaving OUtdoor Droplets) chamber, we investigated the interplay of H 2 SO 4 and HIO x during atmospheric particle nucleation. We found that HIO x greatly enhances H 2 SO 4 (-NH 3 ) nucleation through two different interactions. First, HIO 3 strongly binds with H 2 SO 4 in charged clusters so they drive particle nucleation synergistically. Second, HIO 2 substitutes for NH 3 , forming strongly bound H 2 SO 4 -HIO 2 acid-base pairs in molecular clusters. Global observations imply that HIO x is enhancing H 2 SO 4 (-NH 3 ) nucleation rates 10- to 10,000-fold in marine and polar regions.

Recently, the NANOGrav, PPTA, EPTA, and CPTA Collaborations independently reported their evidence of the Stochastic Gravitational Waves Background (SGWB). While the inferred gravitational-wave background amplitude and spectrum are consistent with astrophysical expectations for a signal from the population of supermassive black-hole binaries (SMBHBs), the search for new physics remains plausible in this observational window. In this work, we explore the possibility of explaining such a signal by the scalar-induced gravitational waves (IGWs) in the very early universe. We use a parameterized broken power-law function as a general description of the energy spectrum of the SGWB and fit it to the new results of NANOGrav, PPTA and EPTA. We find that this approach can put constraints on the parameters of IGW energy spectrum and further yield restrictions on various inflation models that may produce primordial black holes (PBHs) in the early universe, which is also expected to be examined by the forthcoming space-based GW experiments., (Copyright © 2023 Science China Press. Published by Elsevier B.V. All rights reserved.)

Zanthoxylum motuoense (Tibetan prickly ash, MTHJ), different from the Chinese prickly ash species, is distributed only in the Tibet. Now the chemical characterization and antibacterial activity of MTHJ extracts were analyzed for the first time. As a result, Schinifoline (12) , γ -Fagarine (8) , ( 2E,7E,9E )-6 S-Hydroxy- N -(2-methylpropyl)-11-oxo-2, 7, 9-Dodecatrienamide (6) , and Neoechinulin A (17) were found to be the major different factors by untarget LC-MS metabolomics together with quantitative analysis on target. These four compounds were also the major antibacterial constituents. Then, the antimicrobial activity of MTHJ fractions was evaluated with colony forming units (CFU), fluorescence microscopy imaging, SEM and investigating the potential food preservation. Nutritional composition, colour and sensory evaluation of extract-treated samples were evaluated along storage time. The results suggested the MTHJ may be used for meat products preservation, and the scores were significantly higher for its unique flavor, which offered a promising choice for food safety, preservation and reducing foodborne illness., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

This study used nasal lavage fluid for metabolomics to explore its feasibility, and applied it to the clinical metabolomics study of Xiaoqinglong Decoction in the treatment of allergic rhinitis(AR), aiming to investigate the molecular mechanism of Xiaoqing-long Decoction in the treatment of AR through differential changes in local nasal metabolism. AR patients were selected as the research subjects, and nasal lavage fluid was collected as the sample. Metabolomics analysis using liquid chromatography-mass spectrometry was performed on normal group, AR group, and Xiaoqinglong Decoction group. The differences in metabolic profiles among the groups were compared using principal component analysis and partial least squares discriminant analysis, and differential metabolites were identified and subjected to corresponding metabolic pathway analysis. The results showed that Xiaoqinglong Decoction significantly improved the symptoms of AR patients. The metabolomics analysis revealed 20 differential metabolites between AR group and Xiaoqinglong Decoction group. The core metabolite with a trending return in comparison to normal group was trimethyladipic acid. The metabolites were involved in multiple pathways, including β-alanine metabolism, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. The feasibility of applying nasal lavage fluid in nasal metabolomics was preliminarily demonstrated. Differential metabolites and enriched pathways in the treatment of AR patients with Xiaoqinglong Decoction were identified, indicating that it may improve rhinitis symptoms through the regulation of various metabolites, including antioxidant effects and correction of Th1/Th2 imbalance.

Herein, a direct cross-dehydrogenative C-H amination of indoles has been successfully achieved, enabled by the merger of photocatalysis with nickel catalysis. This developed process does not require stoichiometric oxidants and prefunctionalization of amine partners, providing a concise platform for C-N bond formation. Moreover, the synthetic practicality of this transformation was well revealed by its high step- and atom-economy, high reaction efficiency, and broad functional group tolerance.

Traumatic brain injury usually triggers glial scar formation, neuroinflammation, and neurodegeneration. However, the molecular mechanisms underlying these pathological features are largely unknown. Using a mouse model of hippocampal stab injury (HSI), we observed that miR-331, a brain-enriched microRNA, was significantly downregulated in the early stage (0-7 days) of HSI. Intranasal administration of agomir-331, an upgraded product of miR-331 mimics, suppressed reactive gliosis and neuronal apoptosis and improved cognitive function in HSI mice. Finally, we identified IL-1β as a direct downstream target of miR-331, and agomir-331 treatment significantly reduced IL-1β levels in the hippocampus after acute injury. Our findings highlight, for the first time, agomir-331 as a pivotal neuroprotective agent for early rehabilitation of HSI.

Background: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa that is mediated by immunoglobulin E (IgE). Xiao-qing-long-tang (XQLT) is a traditional Chinese medicine compound that is widely used to treat respiratory diseases such as AR. However, the underlying mechanism of the effect of XQLT on AR remains unclear., Purpose: To elucidate the effect of XQLT on ovalbumin (OVA)-induced AR and the mechanisms of action., Methods: The therapeutic efficacy of XQLT was evaluated in a well-established OVA-induced AR mouse model. Nasal symptoms were analyzed, type 2 cytokines and OVA-sIgE levels were measured, nasal mucosa tissues were collected for histological analysis, and the changes of Group 2 innate lymphoid cells (ILC2s) and the IL-33/ST2 and JAK/STAT signaling pathways in the nasal mucosa were observed., Results: XQLT significantly alleviated the nasal symptoms and histological damage to the nasal mucosa in AR mice, and reduced the levels of type 2 cytokines and OVA-sIgE. In addition, after XQLT treatment, the numbers of ILC2s in the nasal mucosa of AR mice were reduced, and the mRNA levels of the transcription factors GATA3 and ROR-α were decreased. Moreover, IL-33/ST2 signaling pathway was inhibited. The costimulatory cytokine associated JAK/STAT signaling pathway was also inhibited in ILC2s., Conclusion: Our study demonstrated that XQLT regulated ILC2s through the IL-33/ST2 and JAK/STAT pathways to ameliorate type 2 inflammation in OVA-induced AR. These findings suggest that XQLT might be used to treat AR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier GmbH.)

Biogenic vapors form new particles in the atmosphere, affecting global climate. The contributions of monoterpenes and isoprene to new particle formation (NPF) have been extensively studied. However, sesquiterpenes have received little attention despite a potentially important role due to their high molecular weight. Via chamber experiments performed under atmospheric conditions, we report biogenic NPF resulting from the oxidation of pure mixtures of β-caryophyllene, α-pinene, and isoprene, which produces oxygenated compounds over a wide range of volatilities. We find that a class of vapors termed ultralow-volatility organic compounds (ULVOCs) are highly efficient nucleators and quantitatively determine NPF efficiency. When compared with a mixture of isoprene and monoterpene alone, adding only 2% sesquiterpene increases the ULVOC yield and doubles the formation rate. Thus, sesquiterpene emissions need to be included in assessments of global aerosol concentrations in pristine climates where biogenic NPF is expected to be a major source of cloud condensation nuclei.

Microglia are the primary source of transglutaminase 2 (TGM2) in the brain; however, the roles of microglial TGM2 in neural development and disease are still not well known. The aim of this study is to elucidate the role and mechanisms of microglial TGM2 in the brain. A mouse line with a specific knockout of Tgm2 in microglia was generated. Immunohistochemistry, Western blot and qRT-PCR assays were performed to evaluate the expression levels of TGM2, PSD-95 and CD68. Confocal imaging, immunofluorescence staining and behavioural analyses were conducted to identify phenotypes of microglial TGM2 deficiency. Finally, RNA sequencing, qRT-PCR and co-culture of neurons and microglia were used to explore the potential mechanisms. Deletion of microglial Tgm2 causes impaired synaptic pruning, reduced anxiety and increased cognitive deficits in mice. At the molecular level, the phagocytic genes, such as Cq1a, C1qb and Tim4, are significantly down-regulated in TGM2-deficient microglia. This study elucidates a novel role of microglial TGM2 in regulating synaptic remodelling and cognitive function, indicating that microglia Tgm2 is essential for proper neural development., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

A Giese reaction of aryl bromides with electron-deficient alkenes was developed, enabled by a dual catalyst system containing Ni II complex and Ir III photocatalyst. This protocol could accommodate a variety of aryl bromides and electron-deficient alkenes, delivering the conjugate adducts in up to 97% yield. The utilization of photoexcited (dtbbpy)Ni II (aryl)Br intermediate as an aryl radical source allows this novel transformation of aryl halides, thus expanding the chemical space of excited nickel catalysis.

The interaction between nitrogen monoxide (NO) and organic peroxy radicals (RO 2 ) greatly impacts the formation of highly oxygenated organic molecules (HOM), the key precursors of secondary organic aerosols. It has been thought that HOM production can be significantly suppressed by NO even at low concentrations. Here, we perform dedicated experiments focusing on HOM formation from monoterpenes at low NO concentrations (0 - 82 pptv). We demonstrate that such low NO can enhance HOM production by modulating the RO 2 loss and favoring the formation of alkoxy radicals that can continue to autoxidize through isomerization. These insights suggest that HOM yields from typical boreal forest emissions can vary between 2.5%-6.5%, and HOM formation will not be completely inhibited even at high NO concentrations. Our findings challenge the notion that NO monotonically reduces HOM yields by extending the knowledge of RO 2 -NO interactions to the low-NO regime. This represents a major advance towards an accurate assessment of HOM budgets, especially in low-NO environments, which prevails in the pre-industrial atmosphere, pristine areas, and the upper boundary layer., (© 2023. The Author(s).)

Iodic acid (IA) has recently been recognized as a key driver for new particle formation (NPF) in marine atmospheres. However, the knowledge of which atmospheric vapors can enhance IA-induced NPF remains limited. The unique halogen bond (XB)-forming capacity of IA makes it difficult to evaluate the enhancing potential (EP) of target compounds on IA-induced NPF based on widely studied sulfuric acid systems. Herein, we employed a three-step procedure to evaluate the EP of potential atmospheric nucleation precursors on IA-induced NPF. First, we evaluated the EP of 63 precursors by simulating the formation free energies (Δ G ) of the IA-containing dimer clusters. Among all dimer clusters, 44 contained XBs, demonstrating that XBs are frequently formed. Based on the calculated Δ G values, a quantitative structure-activity relationship model was developed for evaluating the EP of other precursors. Second, amines and O/S-atom-containing acids were found to have high EP, with diethylamine (DEA) yielding the highest potential to enhance IA-induced nucleation by combining both the calculated Δ G and atmospheric concentration of considered 63 precursors. Finally, by studying larger (IA) 1-3 (DEA) 1-3 clusters, we found that the IA-DEA system with merely 0.1 ppt (2.5×10 6 cm -3 ) DEA yields comparable nucleation rates to that of the IA-iodous acid system.

Rationale: Gastric cancer (GC) is one of the most common malignancies globally, and its occurrence and development are associated with genetic, dietary, biological, and immune factors. Epstein-Barr virus-associated gastric cancer (EBVaGC), as a special subtype of GC, has become a research hotspot in recent years. In patients with advanced GC, Epstein-Barr virus infection is closely related to lymph node metastasis, depth of tumor invasion, and poor prognosis. There is great clinical need for a new treatment modality for EBVaGC. Advances in molecular biology and cancer genetics have led to the development of immune checkpoint inhibitors (ICIs); patients treated with ICIs experience clinical benefit and few adverse effects., Patient Concerns and Diagnoses: We report a 31-year-old male with advanced EBVaGC and multiple sites of lymph node metastasis who was intolerant to multiple lines of chemotherapy., Interventions and Outcome: After immune checkpoint inhibitor treatment, both primary and metastatic tumors shrank significantly without noticeable adverse reactions. After 21 months of progression-free status, the patient underwent R0 resection., Lessons: This case report provides evidence for the use of ICIs in treating EBVaGC. It also shows that detection of Epstein-Barr virus-encoded small nuclear RNA may be a prognostic factor in gastric cancer., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Chlorine radicals are strong atmospheric oxidants known to play an important role in the depletion of surface ozone and the degradation of methane in the Arctic troposphere. Initial oxidation processes of chlorine produce chlorine oxides, and it has been speculated that the final oxidation steps lead to the formation of chloric (HClO 3 ) and perchloric (HClO 4 ) acids, although these two species have not been detected in the atmosphere. Here, we present atmospheric observations of gas-phase HClO 3 and HClO 4 . Significant levels of HClO 3 were observed during springtime at Greenland (Villum Research Station), Ny-Ålesund research station and over the central Arctic Ocean, on-board research vessel Polarstern during the Multidisciplinary drifting Observatory for the Study of the Arctic Climate (MOSAiC) campaign, with estimated concentrations up to 7 × 10 6 molecule cm -3 . The increase in HClO 3 , concomitantly with that in HClO 4 , was linked to the increase in bromine levels. These observations indicated that bromine chemistry enhances the formation of OClO, which is subsequently oxidized into HClO 3 and HClO 4 by hydroxyl radicals. HClO 3 and HClO 4 are not photoactive and therefore their loss through heterogeneous uptake on aerosol and snow surfaces can function as a previously missing atmospheric sink for reactive chlorine, thereby reducing the chlorine-driven oxidation capacity in the Arctic boundary layer. Our study reveals additional chlorine species in the atmosphere, providing further insights into atmospheric chlorine cycling in the polar environment., (© 2023. The Author(s).)

The mechanistic pathway by which high relative humidity (RH) affects gas-particle partitioning remains poorly understood, although many studies report increased secondary organic aerosol (SOA) yields at high RH. Here, we use real-time, molecular measurements of both the gas and particle phase to provide a mechanistic understanding of the effect of RH on the partitioning of biogenic oxidized organic molecules (from α-pinene and isoprene) at low temperatures (243 and 263 K) at the CLOUD chamber at CERN. We observe increases in SOA mass of 45 and 85% with increasing RH from 10-20 to 60-80% at 243 and 263 K, respectively, and attribute it to the increased partitioning of semi-volatile compounds. At 263 K, we measure an increase of a factor 2-4 in the concentration of C 10 H 16 O 2-3 , while the particle-phase concentrations of low-volatility species, such as C 10 H 16 O 6-8 , remain almost constant. This results in a substantial shift in the chemical composition and volatility distribution toward less oxygenated and more volatile species at higher RH (e.g., at 263 K, O/C ratio = 0.55 and 0.40, at RH = 10 and 80%, respectively). By modeling particle growth using an aerosol growth model, which accounts for kinetic limitations, we can explain the enhancement in the semi-volatile fraction through the complementary effect of decreased compound activity and increased bulk-phase diffusivity. Our results highlight the importance of particle water content as a diluting agent and a plasticizer for organic aerosol growth.

Traumatic brain injury usually results in neuronal loss and cognitive deficits. Promoting endogenous neurogenesis has been considered as a viable treatment option to improve functional recovery after TBI. However, neural stem/progenitor cells (NSPCs) in neurogenic regions are often unable to migrate and differentiate into mature neurons at the injury site. Transglutaminase 2 (TGM2) has been identified as a crucial component of neurogenic niche, and significantly dysregulated after TBI. Therefore, we speculate that TGM2 may play an important role in neurogenesis after TBI, and strategies targeting TGM2 to promote endogenous neural regeneration may be applied in TBI therapy. Using a tamoxifen-induced Tgm2 conditional knockout mouse line and a mouse model of stab wound injury, we investigated the role and mechanism of TGM2 in regulating hippocampal neurogenesis after TBI. We found that Tgm2 was highly expressed in adult NSPCs and up-regulated after TBI. Conditional deletion of Tgm2 resulted in the impaired proliferation and differentiation of NSPCs, while Tgm2 overexpression enhanced the abilities of self-renewal, proliferation, differentiation, and migration of NSPCs after TBI. Importantly, injection of lentivirus overexpressing TGM2 significantly promoted hippocampal neurogenesis after TBI. Therefore, TGM2 is a key regulator of hippocampal neurogenesis and a pivotal therapeutic target for intervention following TBI.

Introduction: As one of the most common allergic diseases, allergic rhinitis (AR) has attracted wide attention all over the world. More appropriate treatment of AR should be explored thoroughly. In recent years, traditional Chinese medicine has attracted more attention in AR treatment. As a classical Chinese medicine prescription, Xiaoqinglong decoction (XQLD) has been commonly used in treating AR. Even though its therapeutic effect on AR has been clinically confirmed, more molecular mechanism remains to be further investigated. Our research aimed to investigate the therapeutic mechanism of XQLD for AR management., Methods: The study was evaluated in an ovalbumin sensitized mouse model and liquid chromatography-mass spectrometry was adopted to test the stability of XQLD's effective components., Results: The results confirmed the stability and safety of the effective components of XQLD. XQLD significantly downregulated the expression of HDACs (HDAC1, HDAC3, and HDAC4) and Th2 inflammatory factors (IL4, IL5, and IL13) in AR mice. XQLD and the HDAC inhibitor JNJ-26481585 promoted the expression of epithelial tight junction proteins (claudin-1 and ZO-1) and decreased the expression of mucins (Muc5ac and Muc5b) in the nasal mucosa of AR mice., Conclusions: In conclusion, our findings present the beneficial effects of XQLD on AR and recovery of the nasal epithelium. We also identify the decreased HDAC as a potential target of XQLD for AR treatment. This study provides an important experimental proof for elucidating the therapeutic mechanism of XQLD., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a symptom of the onset of SARS-CoV-2, olfactory dysfunction (OD), has attracted tremendous attention. OD is not only a negative factor for quality of life but also an independent hazard and early biomarker for various diseases, such as Parkinson's and Huntington's diseases. Therefore, early identification and treatment of OD in patients are critical. Many etiological factors are responsible for OD based on current opinions. Sniffin'Sticks are recommended to identify the initial position (central or peripheral) for OD when treating patients clinically. It is worth emphasizing that the olfactory region in nasal cavity is recognized as the primary and critical olfactory receptor. Many nasal diseases, such as those with traumatic, obstructive and inflammatory causes, can lead to OD. The key question is no refined diagnosis or treatment strategy for nasogenic OD currently. This study summarizes the differences in medical history, symptoms, auxiliary examination, treatment and prognosis of different types of nasogenic OD by analyzing the current studies. We propose using olfactory training after 4-6 weeks of initial treatment for nasogenic OD patients with no significant improvement in olfaction. We hope that our research can provide valuable clinical guidance by systematically summarizing the clinical characteristics of nasogenic OD., (© 2023 S. Karger AG, Basel.)

Iodine is a reactive trace element in atmospheric chemistry that destroys ozone and nucleates particles. Iodine emissions have tripled since 1950 and are projected to keep increasing with rising O 3 surface concentrations. Although iodic acid (HIO 3 ) is widespread and forms particles more efficiently than sulfuric acid, its gas-phase formation mechanism remains unresolved. Here, in CLOUD atmospheric simulation chamber experiments that generate iodine radicals at atmospherically relevant rates, we show that iodooxy hypoiodite, IOIO, is efficiently converted into HIO 3 via reactions (R1) IOIO + O 3  → IOIO 4 and (R2) IOIO 4  + H 2 O → HIO 3  + HOI +  (1) O 2 . The laboratory-derived reaction rate coefficients are corroborated by theory and shown to explain field observations of daytime HIO 3 in the remote lower free troposphere. The mechanism provides a missing link between iodine sources and particle formation. Because particulate iodate is readily reduced, recycling iodine back into the gas phase, our results suggest a catalytic role of iodine in aerosol formation., (© 2022. The Author(s).)

Objectives: To establish a nomogram model for the early diagnosis of sepsis in children., Methods: A total of 76 children with sepsis who were admitted to Sichuan Maternal and Child Health Hospital from January 2018 to June 2021 were retrospectively selected as the sepsis group. After matching for sex and age (±2 years) at a ratio of 1:1:1, 76 children with local infection who were hospitalized during the same period were enrolled as the local infection group, and 76 children with non-infectious diseases were enrolled as the control group. The three groups were compared in terms of laboratory markers and the results of quick Sequential Organ Failure Assessment (qSOFA) and Pediatric Critical Illness Score (PCIS). A multivariate logistic regression analysis was used to investigate the association between the above indicators and sepsis. R4.1.3 software was used to establish and validate the nomogram model for the early diagnosis of sepsis based on the results of the multivariate analysis. A receiver operating characteristic (ROC) curve analysis was used to evaluate the value of the nomogram model, and the Bootstrap method was used to perform the internal validation of the model., Results: The multivariate logistic regression analysis showed that soluble triggering receptor expressed on myeloid cells-1, qSOFA score, PCIS score, C-reactive protein, interleukin-6, and interleukin-10 were independently associated with childhood sepsis ( P <0.05). The above indicators were used to establish a nomogram for the early diagnosis of sepsis, with an area under the ROC curve of 0.837 (95% CI : 0.760-0.914), and the calibration curve results showed a mean absolute error of 0.024, suggesting that the performance of this model was basically consistent with that of the ideal model., Conclusions: The indicators soluble triggering receptor expressed on myeloid cells-1, qSOFA score, PCIS score, C-reactive protein, interleukin-6, and interleukin-10 are independently associated with childhood sepsis, and the nomogram model established based on these indicators has high discriminatory ability and accuracy in the early diagnosis of sepsis in children.

Purpose: Current staging criteria for papillary thyroid cancer (PTC) do not include the number of metastatic lymph nodes (LNs), which is highly predictive of survival in multiple cancers. The LN metastasis burden is particularly relevant for older adults with thyroid cancer because of their poor prognosis. We examined a modified staging system for this population utilizing node number (Nn)., Methods: Overall, 14,341 patients aged 55 years or older with stage I-IVB PTC were identified in the 2004-2015 Surveillance, Epidemiology and End Results database. Cox regression models were conducted to test the relationship between positive LN number and PTC-specific survival (PTCSS). Independent training/validation sets were used to derive and validate a new revised TNnM grouping. The 8th edition American Joint Committee on Cancer TNM staging system was compared with TNnM stage by calculating the 10-year PTCSS rates, Harrell's concordance index (C-index), and Akaike's information criterion (AIC)., Results: An increase in number of LN metastases was identified as an independent, negative prognostic factor for PTCSS in multivariate analysis. 10-year PTCSS for stage I-IVB based on the AJCC 8th edition TNM were 98.83%, 93.49%, 71.21%, 72.95%, and 58.52%, respectively, while 10-year PTCSS for the corresponding stage in the TNnM were 98.59%, 92.2%, 83.26%, 75.24%, and 56.73%, respectively. The revised TNnM stage was superior, with a higher C-index and a lower AIC in both the training and validation cohorts., Conclusion: The TNnM staging system for PTC patients ≥ 55 years could be associated with improved outcomes. External validation studies of this system are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Chen, Sun, Tian and He.)

Objective: Bypass yields favorable outcomes in the treatment of Moyamoya disease (MMD). Bloody fluids accumulate between the targeted cortex and the temporal muscle after surgical bypass. These fluids are handled empirically via subcutaneous tubes or conservative treatments. However, substances located in certain positions may adversely affect the establishment of indirect collaterals (ICs) from muscular grafts., Methods: Patients in our hospital from January 2014 to December 2019 were eligible for inclusion. Digital subtraction angiography (DSA) and radiological examinations were used during the perioperative and follow-up periods. Bloody fluid volumes were calculated using computed tomography- (CT-) based 3D Slicer software. The characteristics of bloody fluids, patient demographics, and clinical data were retrospectively analyzed., Results: In total, 110 patients underwent indirect or combined bypass with follow-up DSA. The mean age of the enrolled patients was 42.4 ± 11.8 years. Previous ischemia ( p = 0.001), previous hemorrhage ( p = 0.013), bloody fluid volume ( p = 0.049), and the time of imaging ( p = 0.081) were associated with indirect outcomes. Ordinal regression analysis confirmed that good indirect outcomes were associated with previous ischemia ( p < 0.001) and a large bloody fluid volume ( p = 0.013). Further subgroups based on fluid volume were significantly correlated with IC establishment ( p = 0.030)., Conclusions: A large bloody fluid volume and previous ischemic history were associated with good indirect outcomes. The presence of bloody fluids may reflect impaired degrees of muscular donors due to bipolar electrocoagulation, thus highlighting the importance of appropriate application of bipolar forceps., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Hu, He, Cao, Yu, Fu, Zhou, Hu, Xu, Xu, Wang and Wang.)

Dimethyl sulfide (DMS) influences climate via cloud condensation nuclei (CCN) formation resulting from its oxidation products (mainly methanesulfonic acid, MSA, and sulfuric acid, H 2 SO 4 ). Despite their importance, accurate prediction of MSA and H 2 SO 4 from DMS oxidation remains challenging. With comprehensive experiments carried out in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at CERN, we show that decreasing the temperature from +25 to -10 °C enhances the gas-phase MSA production by an order of magnitude from OH-initiated DMS oxidation, while H 2 SO 4 production is modestly affected. This leads to a gas-phase H 2 SO 4 -to-MSA ratio (H 2 SO 4 /MSA) smaller than one at low temperatures, consistent with field observations in polar regions. With an updated DMS oxidation mechanism, we find that methanesulfinic acid, CH 3 S(O)OH, MSIA, forms large amounts of MSA. Overall, our results reveal that MSA yields are a factor of 2-10 higher than those predicted by the widely used Master Chemical Mechanism (MCMv3.3.1), and the NO x effect is less significant than that of temperature. Our updated mechanism explains the high MSA production rates observed in field observations, especially at low temperatures, thus, substantiating the greater importance of MSA in the natural sulfur cycle and natural CCN formation. Our mechanism will improve the interpretation of present-day and historical gas-phase H 2 SO 4 /MSA measurements.

Nucleation of neutral iodine particles has recently been found to involve both iodic acid (HIO 3 ) and iodous acid (HIO 2 ). However, the precise role of HIO 2 in iodine oxoacid nucleation remains unclear. Herein, we probe such a role by investigating the cluster formation mechanisms and kinetics of (HIO 3 ) m (HIO 2 ) n ( m = 0-4, n = 0-4) clusters with quantum chemical calculations and atmospheric cluster dynamics modeling. When compared with HIO 3 , we find that HIO 2 binds more strongly with HIO 3 and also more strongly with HIO 2 . After accounting for ambient vapor concentrations, the fastest nucleation rate is predicted for mixed HIO 3 -HIO 2 clusters rather than for pure HIO 3 or HIO 2 ones. Our calculations reveal that the strong binding results from HIO 2 exhibiting a base behavior (accepting a proton from HIO 3 ) and forming stronger halogen bonds. Moreover, the binding energies of (HIO 3 ) m (HIO 2 ) n clusters show a far more tolerant choice of growth paths when compared with the strict stoichiometry required for sulfuric acid-base nucleation. Our predicted cluster formation rates and dimer concentrations are acceptably consistent with those measured by the Cosmic Leaving Outdoor Droplets (CLOUD) experiment. This study suggests that HIO 2 could facilitate the nucleation of other acids beyond HIO 3 in regions where base vapors such as ammonia or amines are scarce.

Background & Aims: Vacuole membrane protein 1 (VMP1) is an endoplasmic reticulum (ER) transmembrane protein that regulates the formation of autophagosomes and lipid droplets. Recent evidence suggests that VMP1 plays a critical role in lipoprotein secretion in zebra fish and cultured cells. However, the pathophysiological roles and mechanisms by which VMP1 regulates lipoprotein secretion and lipid accumulation in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are unknown., Methods: Liver-specific and hepatocyte-specific Vmp1 knockout mice as well as Vmp1 knock-in mice were generated by crossing Vmp1 flox or Vmp1 KI mice with albumin-Cre mice or by injecting AAV8-TBG-cre, respectively. Lipid and energy metabolism in these mice were characterized by metabolomic and transcriptome analyses. Mice with hepatic overexpression of VMP1 who were fed a NASH diet were also characterized., Results: Hepatocyte-specific deletion of Vmp1 severely impaired VLDL secretion resulting in massive hepatic steatosis, hepatocyte death, inflammation and fibrosis, which are hallmarks of NASH. Mechanistically, loss of Vmp1 led to decreased hepatic levels of phosphatidylcholine and phosphatidylethanolamine as well as to changes in phospholipid composition. Deletion of Vmp1 in mouse liver also led to the accumulation of neutral lipids in the ER bilayer and impaired mitochondrial beta-oxidation. Overexpression of VMP1 ameliorated steatosis in diet-induced NASH by improving VLDL secretion. Importantly, we also showed that decreased liver VMP1 is associated with NAFLD/NASH in humans., Conclusions: Our results provide novel insights on the role of VMP1 in regulating hepatic phospholipid synthesis and lipoprotein secretion in the pathogenesis of NAFLD/NASH., Lay Summary: Non-alcoholic fatty liver disease and its more severe form, non-alcoholic steatohepatitis, are associated with a build-up of fat in the liver (steatosis). However, the exact mechanisms that underly steatosis in patients are not completely understood. Herein, the authors identified that the lack of a protein called VMP1 impairs the secretion and metabolism of fats in the liver and could therefore contribute to the development and progression of non-alcoholic fatty liver disease., Competing Interests: Conflict of interest The authors who have taken part in this study declare that they have nothing to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

A photoinduced, photocatalyst-free cyanoalkylation of nitrostyenes was explored, affording a series of cyanoalkylated alkenes in moderate to good yields. Mechanistic studies reveal that an electron donor-acceptor complex formed between O -aryl oximes and DIPEA is presumably involved in this process. The excellent functional group compatibility of this newly designed synthetic protocol allows for cyanoalkylation of structurally varied substrates, which offers an eco-friendly pathway for the assembly of cyanoalkylated alkenes.

The embryonic ectoderm development (EED) is a core component of the polycomb-repressive complex 2 (PRC2) whose mutations are linked to neurodevelopmental abnormalities, intellectual disability, and neurodegeneration. Although EED has been extensively studied in neural stem cells and oligodendrocytes, its role in microglia is incompletely understood. Here, we show that microglial EED is essential for synaptic pruning during the postnatal stage of brain development. The absence of microglial EED at early postnatal stages resulted in reduced spines and impaired synapse density in the hippocampus at adulthood, accompanied by upregulated expression of phagocytosis-related genes in microglia. As a result, deletion of microglial Eed impaired hippocampus-dependent learning and memory in mice. These results suggest that microglial EED is critical for normal synaptic and cognitive functions during postnatal development., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)