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Background: Chronic pruritus (CP) is a poorly characterized condition associated with intense pruritus without a primary skin eruption. This condition tends to emerge more commonly in older adults, and there is limited research on triggering factors. Objective: To explore the clinical characteristics and pathophysiology of CP following exposure to an immune stimulus. Methods: Clinical characteristics and plasma samples were collected from 15 patients who developed CP following an immune stimulus such as checkpoint inhibitors or vaccination. A multiplex panel was used to analyze plasma cytokine concentrations within these patients. Results: Most immunotherapy-treated patients experienced CP during treatment or after 21 to 60 days of receiving treatment, while vaccine-stimulated patients developed pruritus within a week of vaccination. Plasma cytokine analysis revealed elevated levels of 12 cytokines in patients with immune-stimulated CP compared to healthy controls. Notably, T helper 2 (Th2) related cytokines interleukin (IL)-5 (fold change 2.65; q

Ammonia (NH3) has major effects on the environment and climate. In situ measurements of NH3 concentrations taken between June 2009 and July 2020 at an urban site in Beijing were analyzed to study its long-term behavior, responses to meteorological conditions, and influences on the formation of secondary inorganic aerosols (SIAs). The 11-year average NH3 mixing ratio was 26.9±19.3 ppb (median 23.5 ppb). The annual average NH3 mixing ratio increased from 2009 to 2017 by 50 % and then decreased by 49 % from 2017 to 2020. Notably, the long-term trend for NH3 at the ground level did not align with the trends derived from satellite observations and emission estimates. The NH3 concentration exhibited a stronger correlation with the daily variation in water vapor (H2O) concentration than with air temperature. Thermodynamic modeling revealed the nonlinear response of SIAs to NH3, with increased sensitivity when its concentration was reduced to 40 % of the initial level. Although reducing NH3 concentrations can improve air quality during winter, controlling acid gas concentrations has a greater effect than controlling NH3 concentrations on reducing SIA concentrations, until NH3 and acidic gas concentrations are reduced below 80 % of their current levels. Nevertheless, the increased mass proportion of ammonium salts in SIAs during the observation period indicates that future control measures for NH3 concentrations may need to be prioritized in Beijing.

Abstract Head and neck squamous cell carcinomas (HNSCCs) are cancers that arise in the mucosa of the upper aerodigestive tract. The five-year patient survival rate is ~50%. Treatment includes surgery, radiation, and/or chemotherapy and is associated with lasting effects even when successful in irradicating the disease. New molecular targets and therapies must be identified to improve outcomes for HNSCC patients. We recently identified bitter taste receptors (taste family 2 receptors, or T2Rs) as a novel candidate family of receptors that activate apoptosis in HNSCC cells through mitochondrial Ca2+ overload and depolarization. We hypothesized that targeting another component of tumor cell metabolism, namely glycolysis, may increase the efficacy of T2R-directed therapies. GLUT1 (SLC2A1) is a facilitated-diffusion glucose transporter expressed by many cancer cells to fuel their increased rates of glycolysis. GLUT1 is already being investigated as a possible cancer target, but studies in HNSCCs are limited. Examination of immortalized HNSCC cells, patient samples, and The Cancer Genome Atlas revealed high expression of GLUT1 and upregulation in some patient tumor samples. HNSCC cells and tumor tissue express GLUT1 on the plasma membrane and within the cytoplasm (perinuclear, likely co-localized with the Golgi apparatus). We investigated the effects of a recently developed small molecule inhibitor of GLUT1, BAY-876. This compound decreased HNSCC glucose uptake, viability, and metabolism and induced apoptosis. Moreover, BAY-876 had enhanced effects on apoptosis when combined at low concentrations with T2R bitter taste receptor agonists. Notably, BAY-876 also decreased TNFα-induced IL-8 production, indicating an additional mechanism of possible tumor-suppressive effects. Our study demonstrates that targeting GLUT1 via BAY-876 to kill HNSCC cells, particularly in combination with T2R agonists, is a potential novel treatment strategy worth exploring further in future translational studies.

Abstract Chronic pruritus of unknown origin (CPUO) is characterized by chronic itch for 6 weeks or greater without an identifiable primary cause. Studies are needed to investigate circulating blood biomarkers to elucidate disease pathogenesis. The objective of this study was to investigate changes in circulating blood metabolites in CPUO patients and to identify potential therapeutic targets. Our cross-sectional study collected plasma from 11 CPUO patients and 11 matched control patients for mass-spectrometry based metabolite data analysis. 15 metabolites differed significantly in the blood of CPUO patients compared to controls, including nine amino acids (isoleucine, L-tyrosine, threonine, DL-tryptophan, L-valine, methionine, glycine, lysine, and L-phenylalanine), four amino acid derivatives (creatinine, DL-carnitine, acetyl-L-carnitine, and indole-3-acrylic acid), and two aromatic and fatty acid derivatives (2-hydroxycinnamic acid and oleamide). These metabolites were also correlated with itch severity. Metabolic set enrichment analysis (MSEA) identified downregulation of several pathways in CPUO: phenylalanine, tyrosine, tryptophan biosynthesis; catecholamine biosynthesis; and glycine, serine, and threonine metabolism. Our study identified decreases in several circulating plasma metabolites in CPUO patients and downregulation of pathways related to catecholamine biosynthesis and tryptophan biosynthesis, providing insight into the pathogenesis of CPUO.

Cityscapes contain a variety of objects, each with a particular role in urban administration and development. With the rapid growth and implementation of 3D imaging technology, urban areas are increasingly surveyed with high-resolution point clouds. This technical advancement extensively improves our ability to capture and analyse urban environments and their small objects. Deep learning algorithms for point cloud data have shown considerable capacity in 3D object classification but still face problems with generally under-represented objects (such as light poles or chimneys). This paper introduces the ESTATE dataset (https://github.com/3DOM-FBK/ESTATE), which combines available datasets of various sensors, densities, regions, and object types. It includes 13 classes featuring intensity and/or colour attributes. Tests using ESTATE demonstrate that the dataset improves the classification performance of deep learning techniques and could be a game-changer to advance in the 3D classification of urban objects.

The orientation of crowdsourced and multi-temporal image datasets presents a challenging task for traditional photogrammetry. Indeed, traditional image matching approaches often struggle to find accurate and reliable tie points in images that appear significantly different from one another. In this paper, in order to preserve the memory of the Sycamore Gap tree, a symbol of Hadrian's Wall that was felled in an act of vandalism in September 2023, deep-learning-based features trained specifically on challenging image datasets were employed to overcome limitations of traditional matching approaches. We demonstrate how unordered crowdsourced images and UAV videos can be oriented and used for 3D reconstruction purposes, together with a recently acquired terrestrial laser scanner point cloud for scaling and referencing. This allows the memory of the Sycamore Gap tree to live on and exhibits the potential of photogrammetric AI (Artificial Intelligence) for reverse engineering lost heritage.

The 8.2 ka event has been extensively investigated as a remarkable single event but rarely considered as a part of multi-centennial climatic evolution. Here, we present absolutely dated speleothem multi-proxy records spanning 9.0–7.9 ka from Beijing in North China, near the northern limit of the East Asian summer monsoon (EASM) and thus sensitive to climate change, to provide evidence of the intensified multi-decadal climatic oscillations since 8.52 ka. Three extreme excursions characterized by inter-decadal consecutive δ18O excursions exceeding ±1σ are identified from 8.52 ka in our speleothem record. The earlier two are characterized by enriched 18O at ∼8.50 and 8.20 ka, respectively, suggesting a prolonged arid event, which is supported by the positive trend in δ13C values, increased trace element ratios, and lower growth rate. Following the 8.2 ka event, an excessive rebound immediately emerges in our δ18O and trace element records but moderate in the δ13C, probably suggesting pluvial conditions and nonlinear response of the local ecosystem. Following two similar severe droughts at 8.50 and 8.20 ka, the different behavior of δ13C suggests the recovering degree of resilient ecosystem responding to different rebounded rainfall intensity. A comparison with other high-resolution records suggests that the two droughts–one pluvial pattern between 8.52 and 8.0 ka is of global significance instead of being a regional phenomenon, and is causally linked to the slowdown and acceleration of the Atlantic Meridional Overturning Circulation that was further dominated by the freshwater injections in the North Atlantic.

Photovoltaic power stations utilizing solar energy, have grown in scale, resulting in an increase in operational maintenance requirements. Efficient inspection of components within these stations is crucial. However, the large area of photovoltaic power generation, coupled with a substantial number of photovoltaic panels and complex geographical environments, renders manual inspection methods highly inefficient and inadequate for modern photovoltaic power stations. To address this issue, this paper proposes a method and system for hot spot detection on photovoltaic panels using unmanned aerial vehicles (UAVs) equipped with multispectral cameras. The UAVs capture visible and infrared images of the photovoltaic power plant, which are then processed for photogrammetry to determine imaging position and attitude. The infrared images are stitched together using this information, forming a geographically referenced overall image. Hot spot detection is performed on the infrared images, enabling the identification of faulty photovoltaic panels and facilitating efficient inspection and maintenance. Experimental trials were conducted at a photovoltaic power station in Qingyuan, Guangdong Province China. The results demonstrate the effectiveness of the proposed method in accurately detecting panels with hot spot faults.

Abstract The full data set of the Daya Bay reactor neutrino experiment is used to probe the effect of the charged current non-standard interactions (CC-NSI) on neutrino oscillation experiments. Two different approaches are applied and constraints on the corresponding CC-NSI parameters are obtained with the neutrino flux taken from the Huber-Mueller model with a 5% uncertainty. For the quantum mechanics-based approach (QM-NSI), the constraints on the CC-NSI parameters ϵ eα and ϵ eα s $$ {\epsilon}_{e\alpha}^s $$ are extracted with and without the assumption that the effects of the new physics are the same in the production and detection processes, respectively. The approach based on the weak effective field theory (WEFT-NSI) deals with four types of CC-NSI represented by the parameters [ε X ] eα . For both approaches, the results for the CC-NSI parameters are shown for cases with various fixed values of the CC-NSI and the Dirac CP-violating phases, and when they are allowed to vary freely. We find that constraints on the QM-NSI parameters ϵ eα and ϵ eα s $$ {\epsilon}_{e\alpha}^s $$ from the Daya Bay experiment alone can reach the order O $$ \mathcal{O} $$ (0.01) for the former and O $$ \mathcal{O} $$ (0.1) for the latter, while for WEFT-NSI parameters [ε X ] eα , we obtain O $$ \mathcal{O} $$ (0.1) for both cases.

Abstract Prurigo nodularis (PN) is a chronic inflammatory skin disease that is associated with variability in peripheral blood eosinophil levels and response to T-helper 2 targeted therapies (Th2). Our objective was to determine whether circulating immune profiles with respect to type 2 inflammation differ by race and peripheral blood eosinophil count. Plasma from 56 PN patients and 13 matched healthy controls was assayed for 54 inflammatory biomarkers. We compared biomarker levels between PN and HCs, among PN patients based on absolute eosinophil count, and across racial groups in PN. Eleven biomarkers were elevated in PN versus HCs including interleukin (IL)-12/IL-23p40, tumor necrosis factor-alpha (TNF-α), Thymic stromal lymphopoietin (TSLP), and macrophage-derived chemokine (MDC/CCL22). Additionally, PN patients with AEC > 0.3 K cells/μL had higher Th2 markers (eotaxin, eotaxin-3, TSLP, MCP-4/CCL13), and African American PN patients had lower eosinophils, eotaxin, and eotaxin-3 versus Caucasian and Asian PN patients (p 0.3 K and Asian and Caucasian races are associated with Th2 skewed circulating immune profiles and response to Th2 targeted therapies.

The New Baseline Surface Radiation (NBSR) system was established at the Shangdianzi (SDZ) regional Global Atmosphere Watch (GAW) station in 2013 to observe nine broadband radiation components, i.e. the global, direct, diffuse, and upwelling shortwave irradiance (GSWI, DSWI, DifSWI, and UpSWI); the photosynthetically active radiation (PAR); the ultraviolet irradiance (UVAI and UVBI); and the down- and upwelling longwave irradiance (DnLWI and UpLWI). To test the 1 min raw radiometric data, a Hybrid Algorithm for Radiation Data Quality Control (HARDQC) is presented in this study based on well-established methods, together with the solar irradiance dataset and the spectral features of the instrument bands. Subsequently, a NBSR dataset, which consists of radiation data at multiple timescales (i.e. 1 min, hourly, daily, monthly, monthly average hourly, and monthly average daily) over 2013–2022, is established and evaluated. Results show that more than 98.7 % of all radiation components passed the physical possibility test. The percentages of those that passed the extremely rare test are greater than 98.6 % for all radiation components except for the DnLWI (97.1 %). The percentages of those that passed the comparison test are greater than 83.3 % (GSWI), 78.3 % (DSWI), 81.7 % (DifSWI), 93.1 % (UpSWI), 88.9 % (PAR), 95.6 % (UVAI), 96.3 % (UVBI), 99.8 % (DnLWI), and 99.7 % (UpLWI), respectively. Due to data logger faults, removal of the instruments for calibration, and lightning strikes, some apparent data gaps in the upwelling radiation components (January 2015–August 2017) and all radiation components (December 2018; July to September 2021) were detected. Despite the existence of a few imperfections in the NBSR dataset, it is still reliable to apply it in many fields such as the validation of satellite products and numerical models, the investigation of relationships between radiation and atmospheric composition, and the detection of changes in the surface fluxes. The dataset described in this paper is available at https://doi.org/10.1594/PANGAEA.963330 (Quan et al., 2023b).

In the search of quantum spin liquid (QSL), spin-1/2 triangular-lattice Heisenberg antiferromagnets have always been viewed as fertile soils. Despite the true magnetically ordered ground state, anisotropy has been considered to play a significant role in stabilizing a QSL state. However, the nature and ground state of the most anisotropic case, the triangular-lattice Ising antiferromagnet (TLIAF), remain elusive and controversial. Here, we report specific-heat and thermal-conductivity measurements on a newly discovered Ising-type QSL candidate PrMgAl_{11}O_{19}. At zero field, the magnetic specific heat shows a quadratic temperature dependence. On the contrary, no direct positive magnetic contribution to thermal conductivity is detected, ruling out the presence of mobile gapless fermionic excitations. Further analysis of phonon thermal conductivity reveals that the phonons are strongly scattered by thermally activated magnetic excitations out of a gap, which exhibits a linear dependence with magnetic field. These results demonstrate that the spin-1/2 TLIAF PrMgAl_{11}O_{19} has a gapped Z_{2} QSL ground state.

Abstract Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). Despite having a wide variety of therapeutic agents available for the treatment of MF, patients often suffer from a significant decrease in quality of life and rarely achieve long-term remission or complete cure, highlighting a need to develop novel therapeutic agents for this disease. The present study was undertaken to evaluate the efficacy of a novel anti-tumor agent, GZ17-6.02, which is composed of curcumin, harmine, and isovanillin, against MF in vitro and in murine models. Treatment of HH and MyLa cells with GZ17-6.02 inhibited the growth of both cell lines with IC50 ± standard errors for growth inhibition of 14.37 ± 1.19 µg/mL and 14.56 ± 1.35 µg/mL, respectively, and increased the percentage of cells in late apoptosis (p = .0304 for HH; p = .0301 for MyLa). Transcriptomic and proteomic analyses revealed that GZ17-6.02 suppressed several pathways, including tumor necrosis factor (TNF)-ɑ signaling via nuclear factor (NF)-kB, mammalian target of rapamycin complex (mTORC)1, and Pi3K/Akt/mTOR signaling. In a subcutaneous tumor model, GZ17-6.02 decreased tumor volume (p = .002) and weight (p = .009) compared to control conditions. Proteomic analysis of tumor samples showed that GZ17-6.02 suppressed the expression of several proteins that may promote CTCL growth, including mitogen-activated protein kinase (MAPK)1, MAPK3, Growth factor receptor bound protein (GRB)2, and Mediator of RAP80 interactions and targeting subunit of 40 kDa (MERIT)40.

Abstract Background An incomplete understanding of preterm birth is especially concerning for low-middle income countries, where preterm birth has poorer prognoses. While systemic proinflammatory processes are a reportedly normal component of gestation, excessive inflammation has been demonstrated as a risk factor for preterm birth. There is minimal research on the impact of excessive maternal inflammation in the first trimester on the risk of preterm birth in low-middle income countries specifically. Methods Pregnant women were enrolled at the rural Bangladesh site of the National Institute of Child Health Global Network Maternal Newborn Health Registry. Serum samples were collected to measure concentrations of the inflammatory markers C-reactive protein (CRP) and Alpha-1-acid glycoprotein (AGP), and stool samples were collected and analyzed for enteropathogens. We examined associations of maternal markers in the first-trimester with preterm birth using logistic regression models. CRP and AGP were primarily modeled with a composite inflammation predictor. Results Out of 376 singleton births analyzed, 12.5% were preterm. First trimester inflammation was observed in 58.8% of all births, and was significantly associated with increased odds of preterm birth (adjusted odds ratio [aOR] = 2.23; 95% confidence interval [CI]: 1.03, 5.16), independent of anemia. Maternal vitamin B12 insufficiency (aOR = 3.33; 95% CI: 1.29, 8.21) and maternal anemia (aOR = 2.56; 95% CI: 1.26, 5.17) were also associated with higher odds of preterm birth. Atypical enteropathogenic E. coli detection showed a significant association with elevated AGP levels and was significantly associated with preterm birth (odds ratio [OR] = 2.36; 95% CI: 1.21, 4.57), but not associated with CRP. Conclusions Inflammation, anemia, and vitamin B12 insufficiency in the first trimester were significantly associated with preterm birth in our cohort from rural Bangladesh. Inflammation and anemia were independent predictors of premature birth in this low-middle income setting where inflammation during gestation was widespread. Further research is needed to identify if infections such as enteropathogenic E. coli are a cause of inflammation in the first trimester, and if intervention for infection would decrease preterm birth.

ABSTRACT: Understanding the underlying pleiotropic relationships among growth and body size traits is important for refining breeding strategies in dairy cattle for optimal body size and growth rate. Therefore, we performed single-trait GWAS for monthly-recorded body weight (BW), hip height, body length, and chest girth from birth to 12 mo of age in Holstein animals, followed by stepwise multiple regression of independent or lowly-linked markers from GWAS loci using conditional and joint association analyses (COJO). Subsequently, we conducted a multitrait meta-analysis to detect pleiotropic markers. Based on the single-trait GWAS, we identified 170 significant SNPs, in which 59 of them remained significant after the COJO analyses. The most significant SNP, located at BTA7:3,676,741, explained 2.93% of the total phenotypic variance for BW6 (BW at 6 mo of age). We identified 17 SNPs with potential pleiotropic effects based on the multitrait meta-analyses, which resulted in 3 additional SNPs in comparison to those detected based on the single-trait GWAS. The identified quantitative trait loci regions overlap with genes known to influence human growth-related traits. According to positional and functional analyses, we proposed HMGA2, HNF4G, MED13L, BHLHE40, FRZB, DMP1, TRIB3, and GATAD2A as important candidate genes influencing the studied traits. The combination of single-trait GWAS and meta-analyses of GWAS results improved the efficiency of detecting associated SNPs, and provided new insights into the genetic mechanisms of growth and development in Holstein cattle.

Antibiotic resistance is a growing public health challenge. Antimicrobial peptides (AMPs) effectively target microorganisms through non-specific mechanisms, limiting their ability to develop resistance. Therefore, the prediction and design of new AMPs is crucial. Recently, deep learning has spurred interest in computational approaches to peptide drug discovery. This study presents a novel deep learning framework for AMP classification, function prediction, and generation. We developed discoverAMP (dsAMP), a robust AMP predictor using CNN Attention BiLSTM and transfer learning, which outperforms existing classifiers. In addition, dsAMPGAN, a Generative Adversarial Network (GAN)-based model, generates new AMP candidates. Our results demonstrate the superior performance of dsAMP in terms of sensitivity, specificity, Matthew correlation coefficient, accuracy, precision, F1 score, and area under the ROC curve, achieving >95% classification accuracy with transfer learning on a small dataset. Furthermore, dsAMPGAN successfully synthesizes AMPs similar to natural ones, as confirmed by comparisons of physical and chemical properties. This model serves as a reliable tool for the identification of novel AMPs in clinical settings and supports the development of AMPs to effectively combat antibiotic resistance.

To study the hydrodynamic characteristics of blade trimming length in centrifugal pumps, Delayed Detached Eddy Simulation (DDES) with nonlinear eddy viscosity was utilized to conduct unsteady calculations on the centrifugal pump. A comprehensive examination of the fluid dynamic properties of the centrifugal pump, including external features, flow conditions, and pressure fluctuations, was carried out. By applying the theory of entropy production, the areas of high energy loss within the centrifugal pump were identified, and the correlations between local entropy production, energy loss, and unsteady flow in different areas with varying blade trimming lengths were analyzed. The results indicate that with the increase in blade trimming length, under rated flow conditions, the head decreases by 1.8%, 3.2%, and 5.7% for different blade trimming lengths, respectively, compared to normal impellers. Similarly, the efficiency decreases by 0.5%, 0.8%, and 1.0% for different blade trimming lengths, respectively. Similar trends were observed under other working conditions as well. As the degree of blade trimming increases, the irreversible losses after the failure of the centrifugal pump also increase significantly, indicating that the flow inside the centrifugal pump becomes disorder. Blade trimming leads to a disorderly fluid flow inside the centrifugal pump, causing an increase in the radial force during operation, which in turn leads to an increase in vibration amplitude and affects its operational stability. Blade trimming failure has a significant impact on the frequency and amplitude of pressure pulsation, resulting in abnormal pressure pulsation and abnormal vibration of the centrifugal pump. Therefore, early warning and diagnosis of blade trimming can be achieved through pressure pulsation monitoring.

Abstract Antibiotic resistance or tolerance of pathogens is one of the most serious global public health threats. Bacteria in biofilms show extreme tolerance to almost all antibiotic classes. Thus, use of antibiofilm drugs without bacterial‐killing effects is one of the strategies to combat antibiotic tolerance. In this study, we discovered a coumarin–chalcone conjugate C9, which can inhibit the biofilm formation of three common pathogens that cause nosocomial infections, namely, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli, with the best antibiofilm activity against P. aeruginosa. Further investigations indicate that C9 decreases the synthesis of the key biofilm matrix exopolysaccharide Psl and bacterial second messenger cyclic‐di‐GMP. Meanwhile, C9 can interfere with the regulation of the quorum sensing (QS) system to reduce the virulence of P. aeruginosa. C9 treatment enhances the sensitivity of biofilm to several antibiotics and reduces the survival rate of P. aeruginosa under starvation or oxidative stress conditions, indicating its excellent potential for use as an antibiofilm‐forming and anti‐QS drug.

Abstract Background Idiopathic pulmonary fibrosis (IPF) bears high mortality due to unclear pathogenesis and limited therapeutic options. Therefore, identifying novel regulators is required to develop alternative therapeutic strategies. Methods The lung fibroblasts from IPF patients and Reticulocalbin 3 (RCN3) fibroblast-selective knockdown mouse model were used to determine the importance of Rcn3 in IPF; the epigenetic analysis and protein interaction assays, including BioID, were used for mechanistic studies. Results Reticulocalbin 3 (RCN3) upregulation is associated with the fibrotic activation of lung fibroblasts from IPF patients and Rcn3 overexpression blunts the antifibrotic effects of pirfenidone and nintedanib. Moreover, repressing Rcn3 expression in mouse fibroblasts ameliorates bleomycin-induced lung fibrosis and pulmonary dysfunction in vivo. Mechanistically, RCN3 promotes fibroblast activation by maintaining persistent activation of TGFβ1 signalling via the TGFβ1-RCN3-TGFBR1 positive feedback loop, in which RCN3 upregulated by TGFβ1 exposure detains EZH2 (an epigenetic methyltransferase) in the cytoplasm through RCN3-EZH2 interaction, leading to the release of the EZH2-H3K27me3 epigenetic repression of TGFBR1 and the persistent expression of TGFBR1. Conclusions These findings introduce a novel regulating mechanism of TGFβ1 signalling in fibroblasts and uncover a critical role of the RCN3-mediated loop in lung fibrosis. RCN3 upregulation may cause resistance to IPF treatment and targeting RCN3 could be a novel approach to ameliorate pulmonary fibrosis. Graphical Abstract

ImportanceDisease models for atopic dermatitis (AD) have primarily focused on understanding underlying environmental, immunologic, and genetic etiologies. However, the role of metabolic mechanisms in AD remains understudied.ObjectiveTo investigate the circulating blood metabolomic and cytokine profile of AD as compared to healthy control patients.DesignThis study collected plasma from 20 atopic dermatitis with moderate-to-severe itch (score of ≥5 on the itch Numeric Rating Scale and IGA score ≥3) and 24 healthy control patients. Mass-spectrometry based metabolite data were compared between AD and healthy controls. Unsupervised and supervised machine learning algorithms and univariate analysis analyzed metabolic concentrations. Metabolite enrichment and pathway analyses were performed on metabolites with significant fold change between AD and healthy control patients. To investigate the correlation between metabolites levels and cytokines, Spearman’s rank correlation coefficients were calculated between metabolites and cytokines.SettingPatients were recruited from the Johns Hopkins Itch Center and dermatology outpatient clinics in the Johns Hopkins Outpatient Center.ParticipantsThe study included 20 atopic dermatitis patients and 24 healthy control patients.Main outcomes and measuresFold changes of metabolites in AD vs healthy control plasma.ResultsIn patients with AD, amino acids isoleucine, tyrosine, threonine, tryptophan, valine, methionine, and phenylalanine, the amino acid derivatives creatinine, indole-3-acrylic acid, acetyl-L-carnitine, L-carnitine, 2-hydroxycinnamic acid, N-acetylaspartic acid, and the fatty amide oleamide had greater than 2-fold decrease (all P-values

Abstract Background and Aims Patients with end stage kidney disease on hemodialysis are vulnerable to SARS‐CoV‐2 infection. Current guidelines recommend boosters of SARS‐CoV‐2 mRNA‐based vaccines. The long‐term humoral response of hemodialysis patients infected with SARS‐CoV‐2 after receiving a booster of SARS‐CoV‐2 mRNA‐based vaccines has been incompletely characterized. Here, we determined the long‐term humoral response of hemodialysis patients to two and three doses of the Pfizer BioNTech (BNT162b2) mRNA SARS‐CoV‐2 vaccine and investigated the effect of postbooster SARS‐CoV‐2 infection on antibody levels over time. Methods Samples were collected on a monthly basis and tested for anti‐SARS‐CoV‐2 antibodies against anti‐spike S1 domain. Thirty‐five hemodialysis patients were enrolled in the original study and 27 of these received a booster. Patients were followed up to 6 months after the first two doses and an additional 7 months after the third BNT162b2 dose. Results are presented as the internationally harmonized binding antibody units (BAU/mL). Results Antibody level significantly increased from prebooster to 2 weeks postbooster, with a median [25th, 75th percentile] rise from 52.72 [28.55, 184.7] to 6216 [3806, 11,730] BAU/mL in the total population. Of patients with a negative or borderline detectable antibody level 6 months after vaccination who received a third dose, 89% developed positive antibody levels 2 weeks postbooster. Postbooster antibody levels declined an average rate of 29% per month in infection‐naïve patients. Antibody levels spiked in patients infected with SARS‐CoV‐2 after receiving a booster but declined rapidly. No patients infected postbooster required hospitalization. Conclusions A third dose of BNT162b2 restores antibody levels to high levels in dialysis patients but levels decline over time. A third dose did not necessarily prevent infection, but no patients suffered severe infection or required hospitalization. SARS‐CoV‐2 recovered patients appear to have a blunted rise in antibody levels after a third dose. Although patients infected with SARS‐CoV‐2 postbooster had an immediate spike in antibody levels, these declined over time.

Tropospheric ozone (O3) and peroxyacetyl nitrate (PAN) are both photochemical pollutants harmful to the ecological environment and human health. In this study, measurements of O3 and PAN as well as their precursors were conducted from May to July 2019 at Nam Co station (NMC), a highly pristine high-altitude site in the southern Tibetan Plateau (TP), to investigate how distinct transport processes and photochemistry contributed to their variations. Results revealed that, despite highly similar diurnal variations with steep morning rises and flat daytime plateaus that were caused by boundary layer development and downmixing of free-tropospheric air, day-to-day variations in O3 and PAN were in fact controlled by distinct physicochemical processes. During the dry spring season, air masses rich in O3 were associated with high-altitude westerly air masses that entered the TP from the west or the south, which frequently carried high loadings of stratospheric O3 to NMC. During the summer monsoon season, a northward shift of the subtropical jet stream shifted the stratospheric downward entrainment pathway also to the north, leading to direct stratospheric O3 entrainment into the troposphere of the northern TP, which traveled southwards to NMC within low altitudes via northerly winds in front of ridges or closed high pressures over the TP. Westerly and southerly air masses, however, revealed low O3 levels due to the overall less stratospheric O3 within the troposphere of low-latitude regions. PAN, however, was only rich in westerly or southerly air masses that crossed over polluted regions such as northern India, Nepal or Bangladesh before entering the TP and arriving at NMC from the south during both spring and summer. Overall, the O3 level at NMC was mostly determined by stratosphere–troposphere exchange (STE), which explained 77 % and 88 % of the observed O3 concentration in spring and summer, respectively. However, only 0.1 % of the springtime day-to-day O3 variability could be explained by STE processes, while 22 % was explained during summertime. Positive net photochemical formation was estimated for both O3 and PAN based on observation-constrained box modeling. Near-surface photochemical formation was unable to account for the high O3 level observed at NMC, nor was it the determining factor for the day-to-day variability of O3. However, it was able to capture events with elevated PAN concentrations and explain its day-to-day variations. O3 and PAN formation were both highly sensitive to NOx levels, with PAN being also quite sensitive to volatile organic compound (VOC) concentrations. The rapid development of transportation networks and urbanization within the TP may lead to increased emissions and loadings in NOx and VOCs, resulting in strongly enhanced O3 and PAN formation in downwind pristine regions, which should be given greater attention in future studies.

Radix astragali, from the roots of Astragalus L. species, is regarded as an important traditional medicinal plant and has been widely used as a Qi-Invigorating medicine for more than 2 000 years. Considering the different metabolites or functional compounds of Radix astragali from distinct species, the underlying genetic information among the two species is important. Here, we compared the two different root transcriptomes and expression patterns of genes involved in key medicinal secondary metabolites of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao and Astragalus membranaceus (Fisch.) Bge. A total of 98 017 578 and 102 635 956 reads, including 98 294 560 and 92 494 416 high-quality reads, were obtained for A. mongholicus and A. membranaceus, respectively. In general, 73 785 (39.47%) and 60 739 (34.93%) unigenes for A. mongholicus and A. membranaceus were differentially expressed, indicating that the two species had many homologous genes. In comparison, the carbon metabolism category contained the most abundant unigenes in A. mongholicus, and it contained many more genes than those found in A. membranaceus based on the KEGG results. Genes that may participate in the biosynthesis of flavonoids, diterpenoids, triterpenoids, steroids, isoquinoline alkaloids, and carotenoids, such as CHS, F3H, GA3, and CYPs, were identified based on annotations. A total of 5 227 and 5 101 transcription factors (TFs) were identified in A. mongholicus and A. membranaceus, respectively. Three TF categories were found and showed twice as many numbers for A. mongholicus than A. membranaceus, i.e., SOH1 (4:2), LIM (18:5), and GRF (19:5), while MED7 had more unigenes in A. membranaceus (6:12). These results indicated that the different pathways may be involved in the synthesis of active ingredients in the two germplasm resources, and the data obtained will provide valuable information for further utilization and investigation of these two species.

Biofilms are complex microbial communities embedded in extracellular matrix. Pathogens within the biofilm become more resistant to the antibiotics than planktonic counterparts. Novel strategies are required to encounter biofilms. Exopolysaccharides are one of the major components of biofilm matrix and play a vital role in biofilm architecture. In previous studies, a glycosyl hydrolase, PslGPA, from Pseudomonas aeruginosa was found to be able to inhibit biofilm formation by disintegrating exopolysaccharide in biofilms. Here, we investigate the potential spectrum of PslG homologous protein with anti-biofilm activity. One glycosyl hydrolase from Pseudomonas fluorescens, PslGPF, exhibits anti-biofilm activities and the key catalytic residues of PslGPF are conserved with those of PslGPA. PslGPF at concentrations as low as 50 nM efficiently inhibits the biofilm formation of P. aeruginosa and disassemble its preformed biofilm. Furthermore, PslGPF exhibits anti-biofilm activity on a series of Pseudomonads, including P. fluorescens, Pseudomonas stutzeri and Pseudomonas syringae pv. phaseolicola. PslGPF stays active under various temperatures. Our findings suggest that P. fluorescens glycosyl hydrolase PslGPF has potential to be a broad spectrum inhibitor on biofilm formation of a wide range of Pseudomonads.

Scattering characteristic extraction is an essential part of manmade target recognition. However, if two scattering points are in adjacent pixels, scattering characteristic extraction may fail to acquire accurate polarimetric scattering matrices (PSMs) of the weak scattering points due to the contamination caused by the strong scattering points. Target null theory provides a way to solve this problem. By selecting the transmitting and receiving polarization states of radar antennas simultaneously, the echo power of a strong scattering point becomes zero and the contamination effect is avoided. In this paper, a method based on target null theory for scattering characteristic extraction is proposed. First, we optimize the transmitting and receiving polarization states of the radar antenna to suppress the intensities of the strong scattering points to highlight the positions of the weak scattering points in certain polarimetric channels. Second, to suppress the contamination effects of strong scattering points in other polarimetric channels, we establish perturbation correction equations to erase the error generated by the point spread function (PSF) among adjacent scattering points in the radar image. Finally, the solved polarimetric scattering matrices of corresponding positions are implemented for target retrieval. The electromagnetic simulation results demonstrate the effectiveness of the proposed method.

Abstract Pseudomonas aeruginosa is one of the leading nosocomial pathogens that causes both severe acute and chronic infections. The strong capacity of P. aeruginosa to form biofilms can dramatically increase its antibiotic resistance and lead to treatment failure. The biofilm resident bacterial cells display distinct gene expression profiles and phenotypes compared to their free‐living counterparts. Elucidating the genetic determinants of biofilm formation is crucial for the development of antibiofilm drugs. In this study, a high‐throughput transposon‐insertion site sequencing (Tn‐seq) approach was employed to identify novel P. aeruginosa biofilm genetic determinants. When analyzing the novel biofilm regulatory genes, we found that the cell division factor ZapE (PA4438) controls the P. aeruginosa pqs quorum sensing system. The ∆zapE mutant lost fitness against the wild‐type PAO1 strain in biofilms and its production of 2‐heptyl‐3‐hydroxy‐4(1H)‐quinolone (PQS) had been reduced. Further biochemical analysis showed that ZapE interacts with PqsH, which encodes the synthase that converts 2‐heptyl‐4‐quinolone (HHQ) to PQS. In addition, site‐directed mutagenesis of the ATPase active site of ZapE (K72A) abolished the positive regulation of ZapE on PQS signaling. As ZapE is highly conserved among the Pseudomonas group, our study suggests that it is a potential drug target for the control of Pseudomonas infections.

With the development of construction industrialization, green and low-carbon construction methods have been strongly supported by domestic and foreign construction industries. As an efficient lateral force resistance system, the assembled steel plate-concrete composite shear wall structure has gradually become a hotspot in civil engineering. Referring to the node connection method of steel structure, this paper uses the concrete composite shear wall filled with steel plate and extended T-shaped gusset plate to realize the connection between the upper and lower walls, so as to form a T-plate connected assembled composite shear wall structure. Through establishing the refined finite element analysis model of cast-in-place and assembled composite shear wall with the same sizes and comparing the results of them, the feasibility and reliability of the connection method are verified. On this basis, according to the comparison between the bearing and continuity performance of the assembled composite shear wall under different parameters such as the T-plate length, T-plate flange width, T-plate number, joint height and joint longitudinal reinforcement ratio in the node connection area, it is found that the T-plate length, T-plate number and joint height have a great effect on the mechanical properties of assembled composite shear wall, and other parameters are not obvious. In this way, a reasonable recommendation is made for the connection parameters of T-node, which lays a theoretical foundation for promoting the theoretical development and engineering application of this new assembled composite shear wall.

As an excellent local sheep breed in China, Hu sheep have the characteristics of producing more lambs and good motherhood. The purpose of this study was to identify the polymorphism of the mitogen-activated protein kinase 5 (MAP3K5) gene and determine whether it was associated with the body size traits (body height, body length, chest circumference, and cannon circumference) in Hu sheep. The polymorphism of MAP3K5 was identified by using PCR amplification, followed by Sanger sequencing, and KASPar (Kompetitive Allele Specific PCR) technology was used for genotyping subsequently. The results of the association analysis showed that MAP3K5 (g.205261 A > G) was significantly associated with body height at 80, 100, 140, 160, and 180 d; body length at 80 and 160 d; chest circumference at 100, 140, 160, and 180 d; and cannon circumference at 100 and 120 d, respectively. The results of qRT-PCR showed that the expression level of MAP3K5 in the heart was significantly higher (P < 0.05) than in the other 10 tissues. In summary, the MAP3K5 mutation loci may be used as a candidate molecular marker for the body size traits of Hu sheep.

In numerical weather prediction (NWP) models, physical parameterization schemes are the most computationally expensive components, despite being greatly simplified. In the past few years, an increasing number of studies have demonstrated that machine learning (ML) parameterizations of subgrid physics have the potential to accelerate and even outperform conventional physics-based schemes. However, as the ML models are commonly implemented using the ML libraries written in Python, very few ML-based parameterizations have been successfully integrated with NWP models due to the difficulty of embedding Python functions into Fortran-based NWP models. To address this issue, we developed a coupler to allow the ML-based parameterizations to be coupled with a widely used NWP model, i.e., the Weather Research and Forecasting (WRF) model. Similar to the WRF I/O methodologies, the coupler provides the options to run the ML model inference with exclusive processors or the same processors for WRF calculations. In addition, to demonstrate the effectiveness of the coupler, the ML-based radiation emulators are trained and coupled with the WRF model successfully.

Abstract Spaceflight and simulated spaceflight microgravity induced osteoarthritic-like alterations at the transcriptomic and proteomic levels in the articular and meniscal cartilages of rodents. But little is known about the effect of spaceflight or simulated spaceflight microgravity on the transcriptome of tissue-engineered cartilage developed from human cells. In this study, we investigate the effect of simulated spaceflight microgravity facilitated by parabolic flights on tissue-engineered cartilage developed from in vitro chondrogenesis of human bone marrow mesenchymal stem cells obtained from age-matched female and male donors. The successful induction of cartilage-like tissue was confirmed by the expression of well-demonstrated chondrogenic markers. Our bulk transcriptome data via RNA sequencing demonstrated that parabolic flight altered mostly fundamental biological processes, and the modulation of the transcriptome profile showed sex-dependent differences. The secretome profile analysis revealed that two genes (WNT7B and WNT9A) from the Wnt-signaling pathway, which is implicated in osteoarthritis development, were only up-regulated for female donors. The results of this study showed that the engineered cartilage tissues responded to microgravity in a sex-dependent manner, and the reported data offers a strong foundation to further explore the underlying mechanisms.

Abstract Tropical cyclones (TCs) are known to bring heavy rainfall, strong winds and severe storm surges simultaneously, resulting in tremendous damage beyond the effects of a single hazard. However, the compound impacts of TC multi‐hazards remain unexplored in macroeconomic assessments. Here, we provide empirical evidence on the multi‐hazard economic losses of TC for the first time. We used a national panel of provincial economic output in China over 2000–2020. Our results show that the total macroeconomic impact of the severest TC multi‐hazards can represent up to 14 times the value of merely TC winds. Specifically, the vast majority (over 80%) of the combined TC impacts is caused by precipitation, with wider and greater economic impacts than TC winds and storm surges. Furthermore, high‐latitude and interior regions of China are more vulnerable to TCs due to the interactions with temperature variability and TC wind intensity variability. High‐income areas and secondary industries respond markedly to all TC hazards, and the economic impact of TC precipitation is significant over all sectors. Our findings provide new implications for the socio‐economic impact mechanisms of multiple hazards of TCs and valuable insights into the design of climate policy for compound hazard risks.

There is no vaccine to protect from cryptosporidiosis, a leading cause of diarrhea in infants in low- and middle-income countries. Here, we comprehensively identified parasite antigens associated with protection from reinfection. A Cryptosporidium protein microarray was constructed by in vitro transcription and translation of 1,761 C. parvum, C. hominis, or C. meleagridis antigens, including proteins with a signal peptide and/or a transmembrane domain. Plasma IgG and/or IgA from Bangladeshi children longitudinally followed for cryptosporidiosis from birth to 3 years of age allowed for identification of 233 seroreactive proteins. Seven of these were associated with protection from reinfection. These included Cp23, Cp17, Gp900, and 4 additional antigens — CpSMP1, CpMuc8, CpCorA and CpCCDC1. Infection in the first year of life, however, often resulted in no detectable antigen-specific antibody response, and antibody responses, when detected, were specific to the infecting parasite genotype and decayed in the months after infection. In conclusion, humoral immune responses against specific parasite antigens were associated with acquired immunity. While antibody decay over time and parasite genotype-specificity may limit natural immunity, this work serves as a foundation for antigen selection for vaccine design.

Enhancements of stationary planetary waves (SPWs) and traveling planetary waves (TPWs) are commonly observed in the middle atmosphere during sudden stratospheric warming (SSW) events. Based on the least squares fitting method (Wu et al., 1995), numerous studies have used satellite measurements to investigate the characteristics of TPWs during SSWs, but they have ignored the effect of the SPWs. However, a rapid and large change in the SPWs during SSWs may lead to significant disturbances in the amplitude of derived TPWs. In this study, we present a new methodology for obtaining the amplitudes and wave numbers of traveling quasi-5-day oscillations (Q5DOs) in the middle atmosphere during major SSWs. Our new fitting method is developed by inhibiting the effect of a rapid and large change in SPWs during SSWs. We demonstrate the effectiveness of the new method using both synthetic data and satellite observations. The results of the simulations indicate that the new method can suppress the aliasing from SPWs and capture the real variations in TPWs during SSWs. Based on the geopotential height data measured by the Aura satellite from 2004 to 2021, the variations in traveling Q5DOs during eight midwinter major SSWs are reevaluated using the new method. The differences in the fitted amplitudes between the least squares fitting method and the new method are usually over 100 m during the SSW onsets. Our analysis indicates that previously reported Q5DOs during SSWs might be contaminated by SPWs, leading to both overestimation and underestimation of the amplitudes of the traveling Q5DOs.

Strict air pollution control strategies have been implemented in recent decades in the North China Plain (NCP), previously one of the most polluted regions in the world, and have resulted in considerable changes in emissions of air pollutants. However, little is so far known about the long-term trends of the regional background level of NOx and SO2, along with the increase and decrease processes of regional emissions. In this study, the seasonal and diurnal variations of NOx and SO2 as well as their long-term trends at a regional background station in the NCP were characterized from 2004 to 2016. On average, SO2 and NOx mixing ratios were 5.7 ± 8.4 and 14.2 ± 12.4 ppb, respectively. The seasonal variations in SO2 and NOx mixing ratios showed a similar pattern, with a peak in winter and a valley in summer. However, the diurnal variations in SO2 and NOx mixing ratios greatly differed for all seasons, indicating different sources for SO2 and NOx and meteorological effects on their concentrations. Overall, the annual mean SO2 exhibited a significant decreasing trend of −6.1 % yr−1 (R = −0.84, P < 0.01) from 2004 to 2016, which is very close to −6.3 % yr−1 of the annual SO2 emission in Beijing, and a greater decreasing trend of −7.4 % yr−1 (R = −0.95, P < 0.01) from 2008 to 2016. The annual mean of NOx showed a fluctuating rise of +3.4 % yr−1 (R = 0.38, P = 0.40) from 2005 to 2010, reaching the peak value (16.9 ppb) in 2010, and then exhibited an extremely significant fluctuating downward trend of −4.5 % yr−1 (R = 0.95, P < 0.01) from 2010 to 2016. After 2010, the annual mean NOx mixing ratios correlated significantly (R = 0.94, P < 0.01) with the annual NOx emission in North China. The decreasing rate (−4.8 % yr−1, R = −0.92, P < 0.01) of the annual mean NOx mixing ratios from 2011 to 2016 at the Shangdianzi (SDZ) regional atmospheric background station is lower than the one (−8.8 % yr−1, R = −0.94, P < 0.01) for the annual NOx emission in the NCP and in Beijing (−9.0 % yr−1, R = −0.96, P < 0.01). This indicated that surface NOx mixing ratios at SDZ had a weaker influence than SO2 on the emission reduction in Beijing and its surrounding areas in the NCP. The increase in the number of motor vehicles led to an increase in traffic emissions for NOx. This study supported conclusions from previous studies that the measures taken for controlling NOx and SO2 in the NCP in the past decades were generally successful. However, NOx emission control should be strengthened in the future.

Typhoon-related precipitation over land can result in severe disasters such as floods and landslides, and satellites are a valuable tool for estimating surface precipitation with high spatial-temporal resolutions. Accordingly, this study develops a surface precipitation integration framework to combine high-resolution observations from the radiometers of two geostationary satellites, Fengyun-4A (F4) and Himawari-8 (H8), with high-density rain-gauge observations or IMERG data and atmospheric reanalysis data based on a random forest (RF) algorithm. The RF algorithm integrates cloud and atmospheric features from radiometric observations and reanalysis information, and the intensity and spatial distribution of precipitation can be revealed by high-density rain-gauge or IMERG data. We take three typhoons that made landfall in South China during 2018 as examples. The F4-based and H8-based results using rain-gauge data as the predictand both show excellent results, yielding correlation coefficients (R) of ∼ 0.75 and probabilities of detection (POD) of ∼ 0.95. In contrast, when IMERG data are used as the predictand, the corresponding R and POD drop to ∼ 0.5 and 0.93, respectively, due to the uncertainties related to IMERG retrievals. By carefully choosing the predictor, our RF algorithm successfully integrates the information from satellite observations, surface measurements and atmospheric reanalyses, resulting in precipitation estimates that are highly consistent with actual ground observations. Consequently, our proposed integration framework can reconstruct hourly surface precipitation estimates at high spatial-temporal resolutions for historical typhoon studies.

A new turbulent model based on Delayed Detached Eddy Simulation (DDES) with non-linear eddy viscosity model (NLEVM) was developed to predict the complex turbulent flow. The numerical simulation of the triangular cylinder and the centrifugal pump was carried out to investigate the ability and applicability of the DDES model based on NLEVM (DDES_NL). Compared to the turbulent model based on the eddy viscosity model, the computational results of the triangular cylinder showed the advantage of the non-linear eddy viscosity modification in the DDES_NL model which can improve the accuracy of the prediction in the flow phenomenon with a relatively simple turbulence structure. Regrettably, some small-scale turbulent structures among those still cannot be captured accurately. The numerical simulation of the centrifugal pump predicted by the DDES_NL model shows more abundant flow structures and gets close to the realistic statistical characteristics. It also proves the good applicability of the DDES_NL model in complex flow. This study aims to contribute to the growing area of turbulence modeling by exploring it.

For the existing hyperspectral image (HSI) band selection (BS) algorithm does not consider the strong correlation between adjacent bands and does not meet the high-precision extraction of single target, a HSI BS algorithm based on Markov clustering and target land-type spectral difference measurement is proposed in this paper. Specifically, when using Markov clustering for band clustering, the inter band correlation information is embedded and the noise or bad channel band breakpoint is set to adaptively divide the optimal band clustering subset. Then, in each cluster, based on the band difference under the supervision of target category, an evaluation criterion function is designed to select the optimal band combination for single target object extraction. The BS algorithm proposed in this paper is called MCLSD for short. Taking ZY-1 02D HSI in Tongnan of Chongqing as experimental data, taking cultivated land as extraction object and the Random Forest as classifier, the classification accuracy of the selected bands is evaluated. In addition, the MCLSD is compared with the improved sparse subspace clustering (ISSC) (Sun et al., 2015), orthogonal projection band selection (OPBS) (Zhang et al., 2018) and sparse nonnegative matrix factorization (SNMF) (Qin and et al., 2015). Experimental results show that the MCLSD algorithm can select the most suitable band for cultivated land extraction and achieve higher classification accuracy. Especially when the number of bands is less than 5, the MCLSD algorithm has significant advantages over ISSC, OPBS and SNMF. So the MCLSD BS method can meet the demand of the high-precision extraction of target features from HSI data.

In the summer of 2018, a comprehensive field campaign, with measurements on HONO and related parameters, was conducted at the foot (150 m a.s.l.) and the summit of Mt. Tai (1534 m a.s.l.) in the central North China Plain (NCP). With the implementation of a 0-D box model, the HONO budget with six additional sources and its role in radical chemistry at the foot station were explored. We found that the model default source, NO + OH, could only reproduce 13 % of the observed HONO, leading to a strong unknown source strength of up to 3 ppbv h−1. Among the additional sources, the NO2 uptake on the ground surface dominated (∼ 70 %) nighttime HONO formation, and its photo-enhanced reaction dominated (∼ 80 %) daytime HONO formation. Their contributions were sensitive to the mixing layer height (MLH) used for the parameterizations, highlighting the importance of a reasonable MLH for exploring ground-level HONO formation in 0-D models and the necessity of gradient measurements. A ΔHONO/ΔNOx ratio of 0.7 % for direct emissions from vehicle exhaust was inferred, and a new method to quantify its contribution to the observations was proposed and discussed. Aerosol-derived sources, including the NO2 uptake on the aerosol surface and the particulate nitrate photolysis, did not lead to significant HONO formation, with their contributions lower than NO + OH. HONO photolysis in the early morning initialized the daytime photochemistry at the foot station. It was also a substantial radical source throughout the daytime, with contributions higher than O3 photolysis to OH initiation. Moreover, we found that OH dominated the atmospheric oxidizing capacity in the daytime, while modeled NO3 appeared to be significant at night. Peaks of modeled NO3 time series and average diurnal variation reached 22 and 9 pptv, respectively. NO3-induced reactions contribute 18 % of nitrate formation potential (P(HNO3)) and 11 % of the isoprene (C5H8) oxidation throughout the whole day. At night, NO3 chemistry led to 51 % and 44 % of P(HNO3) or the C5H8 oxidation, respectively, implying that NO3 chemistry could significantly affect nighttime secondary organic and inorganic aerosol formation in this high-O3 region. Considering the severe O3 pollution in the NCP and the very limited NO3 measurements, we suggest that besides direct measurements of HOx and primary HOx precursors (O3, HONO, alkenes, etc.), NO3 measurements should be conducted to understand the atmospheric oxidizing capacity and air pollution formation in this and similar regions.

Photochemical pollution over the North China Plain (NCP) is attracting much concern. We usually view peroxyacetyl nitrate (PAN) as the second most important photochemical pollutant featuring high mixing ratios during warm seasons. Our observations at a background site in the NCP identified high PAN concentrations, even during haze events in autumn. The substantial increasing ratios of PAN, by 244 % and 178 %, over the morning hours (08:00–12:00 local time) on 20 and 25 October 2020 were 10.6 and 7.7 times larger than those on clean days. Polluted days are characterized by higher temperature, higher humidity, and anomalous southerly winds compared with clean days. Enhanced local photochemistry has been identified as being the dominant factor that controls the PAN increase in the morning at the rural site, as the time when prevailing wind turns to a southerly wind is too late to promote direct transport of PAN from the polluted urban region. By removing the effect of direct transport of PAN, we provide a quantitative assessment of net PAN chemical production rate of 0.45 ppb h−1 for the mornings of polluted days, also demonstrating the strong local photochemistry. Using observations and calculated photolysis rates, we find that acetaldehyde oxidation by hydroxyl radical (OH) is the primary pathway of peroxyacetyl radical formation at the rural site. Acetaldehyde concentrations and production rates of HOx (HOx= OH + HO2) on polluted days are 2.8 and 2 times as large as those on clean days, leading to a remarkable increase in PAN in the morning. Formaldehyde (HCHO) photolysis dominates the daytime HOx production, thus contributing to fast photochemistry of PAN. Our observational results suggest the cause of a rapid increase in PAN during haze events in autumn at a rural site of the NCP and provide evidence of important role of HCHO photolysis in secondary pollutants at lower nitrogen oxide emissions. This highlights the urgency of carrying out strict volatile organic compound controls over the NCP during the cold season and not just in summer.

IntroductionEnvironmental enteropathy is an important contributor to childhood malnutrition in the developing world. Chronic exposure to fecal pathogens leads to alteration in intestinal structure and function, resulting in impaired gut immune function, malabsorption, and growth faltering leading to environmental enteropathy.MethodsA community-based intervention study was carried out on children till 24 months of age in Matiari district, Pakistan. Blood and fecal specimens were collected from the enrolled children aged 3–6 and 9 months. A real-time PCR-based TaqMan array card (TAC) was used to detect enteropathogens.ResultsGiardia, Campylobacter spp., enteroaggregative Escherichia coli (EAEC), Enteropathogenic Escherichia coli (EPEC), Enterotoxigenic Escherichia coli (ETEC), and Cryptosporidium spp. were the most prevailing enteropathogens in terms of overall positivity at both time points. Detection of protozoa at enrollment and 9 months was negatively correlated with rate of change in height-for-age Z (ΔHAZ) scores during the first and second years of life. A positive association was found between Giardia, fecal lipocalin (LCN), and alpha 1-Acid Glycoprotein (AGP), while Campylobacter spp. showed positive associations with neopterin (NEO) and myeloperoxidase (MPO).ConclusionProtozoal colonization is associated with a decline in linear growth velocity during the first 2 years of life in children living in Environmental enteric dysfunction (EED) endemic settings. Mechanistic studies exploring the role of cumulative microbial colonization, their adaptations to undernutrition, and their influence on gut homeostasis are required to understand symptomatic enteropathogen-induced growth faltering.

Background: High airway driving pressure is associated with adverse outcomes in critically ill patients receiving mechanical ventilation, but large multicentre studies investigating airway driving pressure during major surgery are lacking. We hypothesised that increased driving pressure is associated with postoperative pulmonary complications in patients undergoing major abdominal surgery. Methods: In this preregistered multicentre retrospective observational cohort study, the authors reviewed major abdominal surgical procedures in 11 hospitals from 2004 to 2018. The primary outcome was a composite of postoperative pulmonary complications, defined as postoperative pneumonia, unplanned tracheal intubation, or prolonged mechanical ventilation for more than 48 h. Associations between intraoperative dynamic driving pressure and outcomes, adjusted for patient and procedural factors, were evaluated. Results: Among 14 218 qualifying cases, 389 (2.7%) experienced postoperative pulmonary complications. After adjustment, the mean dynamic driving pressure was associated with postoperative pulmonary complications (adjusted odds ratio for every 1 cm H2O increase: 1.04; 95% confidence interval [CI], 1.02–1.06; P

Abstract Background and Aims Dialysis patients are extremely vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection with high rates of hospitalization and mortality rates. In January 2021, the University of Virginia Dialysis Program initiated a program‐wide vaccination campaign to administer the Pfizer BioNTech messenger RNA SARS‐CoV‐2 (BNT162b2) vaccine. The aim of this study was to characterize the long‐term time‐dependent decline in humoral immunity in hemodialysis patients. Methods A prospective cohort study measuring serial monthly semiquantitative IgG antibody levels to the SARS‐CoV‐2 spike protein receptor binding domain in fully vaccinated in‐center hemodialysis patients. Samples were collected monthly and tested for anti‐SARS‐CoV‐2 antibodies against the anti‐spike S1 domain for 2–6 months post full vaccination. Results were presented as internationally harmonized binding antibody units (BAU/ml). To analyze the change in antibody levels over time, a linear mixed model with random intercept and random slope was used for longitudinal antibody levels. A multivariable model was used to estimate the slope of antibody levels by adjusting for selected patient characteristics. Based on the estimated intercepts and slopes for each subject from the unadjusted model, 10‐month antibody levels were projected. Results The mean baseline antibody level was 647.59 BAU/ml and 87.88% (29/33) of patients were considered qualitatively positive. Two patients were negative at baseline and an additional two had borderline results. Patient antibody levels declined at an adjusted average rate of 31% per month. At 6 months postvaccination, 40% of patients remaining in the cohort possessed either negative or borderline IgG antibody levels. Projecting future antibody levels suggests that 65% of the cohort will progress to borderline or negative antibody levels at 10 months post full vaccination. Conclusion The long‐term vaccine response following vaccination with the BNT162b2 in hemodialysis patients was characterized. Our data add to the limited pool of data in this patient population and emphasize the critical need for vaccine boosters.

Bacterial biofilms play essential roles in ecological environments and in human health. The spatial heterogeneity of biofilms is crucial to their resistance and collective behavior, while quantitative analysis of these biofilm‐specific features is limited. Here, a microfluidic approach is developed to address this issue. Through a special design of microfluidic chamber and spatially controllable bacteria seeding, biofilms are cultivated with customized semi‐2D structure, which enables quantitative measurements of spatially heterogeneous features with time‐lapse microscopy. The advantages of the proposed method are demonstrated via two examples on biofilm homeostasis and stress response, respectively, where the functionally important spatiotemporal dynamics is delineated. In homeostasis, it is found that Pseudomonas aeruginosa biofilms use spatially organized extracellular matrix to preserve iron chelators within their boundaries while maximizing free sharing within the community. In stress response, the spatial distribution of antibiotics in biofilms and how a change in energy metabolism leads to redistribution of drugs over space are elucidated. The proposed method enables cultivating biofilms formed by a wide range of species and even multiple biofilms, which provides a tractable approach to understanding the spatiotemporal features of biofilms formed by environmentally and clinically important bacteria.

Abstract Antimicrobial copper‐containing surface materials have a great potential of reducing the risks of healthcare‐associated infections (HAIs), but their increased use in hospital facilities may select copper‐resistant strains, causing concerns to antimicrobial resistance management. Here, we describe a long‐term bacterial evolution experiment wherein a non‐pathogenic Pseudomonas strain was subjected to daily transfer in laboratory media with and without copper‐mediated contact killing. The copper treatment sequentially involved two surface materials differing in Cu content and thus contact killing effectiveness: first on brass (Cu 63.5%) and then on pure copper (Cu 99.9%). A gradual increase in bacterial survival rate (or a decrease of killing effectiveness) was observed over time on the related copper surfaces. For the final evolved populations after 320 transfers, 37.8% cells of the copper‐evolved populations were able to survive 60 min on pure copper, whereas populations in the control lines remained sensitive with a survival rate of 0.09% under the same contact killing condition. Genome re‐sequencing revealed ~540 mutations accumulated in the copper lines but only 71, on average, in the control lines (variant frequency > 0.5). The mutagenic activities of Cu+ ions were confirmed by measuring spontaneous mutation rate in a laboratory medium supplemented with copper sulfate at a non‐inhibitory concentration. The copper‐evolved populations have acquired increased resistance to Cu+ ions and tobramycin (an aminoglycoside antibiotic), but showed decreased production of biofilm, exoprotein, and pyoverdine. Together, our data demonstrate the potential of bacteria to evolve prolonged survival on metallic copper, and the long‐term impacts should be considered with increased copper usage in hospital environments.