An actively controllable cascaded proton acceleration driven by a separate 0.8 picosecond (ps) laser is demonstrated in proof-of-principle experiments. MeV protons, initially driven by a femtosecond laser, are further accelerated and focused into a dot structure by an electromagnetic pulse (EMP) on the solenoid, which can be tuned into a ring structure by increasing the ps laser energy. An electrodynamics model is carried out to explain the experimental results and show that the dot-structured proton beam is formed when the outer part of the incident proton beam is optimally focused by the EMP force on the solenoid; otherwise, it is overfocused into a ring structure by a larger EMP. Such a separately controlled mechanism allows precise tuning of the proton beam structures for various applications, such as edge-enhanced proton radiography, proton therapy and pre-injection in traditional accelerators.

Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNP in three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v. 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v. 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.

Depression is highly prevalent in haemodialysis patients, and diet might play an important role. Therefore, we conducted this cross-sectional study to determine the association between dietary fatty acids (FA) consumption and the prevalence of depression in maintenance haemodialysis (MHD) patients. Dietary intake was assessed using a validated FFQ between December 2021 and January 2022. The daily intake of dietary FA was categorised into three groups, and the lowest tertile was used as the reference category. Depression was assessed using the Patient Health Questionnaire-9. Logistic regression and restricted cubic spline (RCS) models were applied to assess the relationship between dietary FA intake and the prevalence of depression. As a result, after adjustment for potential confounders, a higher intake of total FA [odds ratio (OR)T3 vs. T1 = 1·59, 95 % confidence interval (CI) = 1·04, 2·46] and saturated fatty acids (SFA) (ORT3 vs. T1 = 1·83, 95 % CI = 1·19, 2·84) was associated with a higher prevalence of depressive symptoms. Significant positive linear trends were also observed (P < 0·05) except for SFA intake. Similarly, the prevalence of depression in MHD patients increased by 20% (OR = 1.20, 95% CI = 1.01–1.43) for each standard deviation increment in SFA intake. RCS analysis indicated an inverse U-shaped correlation between SFA and depression (Pnonlinear > 0·05). Additionally, the sensitivity analysis produced similar results. Furthermore, no statistically significant association was observed in the subgroup analysis with significant interaction. In conclusion, higher total dietary FA and SFA were positively associated with depressive symptoms among MHD patients. These findings inform future research exploring potential mechanism underlying the association between dietary FA and depressive symptoms in MHD patients.

OBJECTIVES/GOALS: There is a scarcity of research examining the views of Black and Latine HIV care consumers on healthcare experiences that influence medical mistrust. The present qualitative study aims to bridge the existing gaps in the literature pertaining to the experiences of Black and Latine HIV care consumers. METHODS/STUDY POPULATION: We conducted 21 semi-structured interviews with Black and Latine HIV care consumers from November to December 2021 to explore perceptions of provider behaviors that increase or decrease HIV care consumers’ trust and mistrust, experiences of stigma, and behaviors and responses when experiencing medical mistrust. Conventional content analysis was conducted to derive meaning from the narratives shared by participants. RESULTS/ANTICIPATED RESULTS: Provider behaviors that increase HIV care consumers’ mistrust include lack of person-centered care, lack of partnership in health decision making, perceived provider incompetence, lack of adequate follow-up to care, and lack of trustworthiness of providers and organizations. Perceived experiences of intersectional stigma in healthcare included feeling judged and discriminated against by healthcare providers regarding HIV status and observing differential care outcomes and delayed care delivery by race and ethnicity. DISCUSSION/SIGNIFICANCE: Findings can inform the development of provider-level interventions to address medical mistrust.

In order to establish a compact all-optical Thomson scattering source, experimental studies were conducted on the 45 TW Ti: sapphire laser facility. By including a steel wafer, mixed gas, and plasma mirror into a double-exit jet, several mechanisms, such as shock-assisted ionization injection, ionization injection, and driving laser reflection, were integrated into one source. So, the source of complexity was remarkably reduced. Electron bunches with central energy fluctuating from 90 to 160 MeV can be produced. Plasma mirrors were used to reflect the driving laser. The scattering of the reflected laser on the electron bunches led to the generation of X-ray photons. Through comparing the X-ray spots under different experimental conditions, it is confirmed that the X-ray photons are generated by Thomson scattering. For further application, the energy spectra and source size of the Thomson scattering source were measured. The unfolded spectrum contains a large amount of low-energy photons besides a peak near 67 keV. Through importing the electron energy spectrum into the Monte Carlo simulation code, the different contributions of the photons with small and large emitting angles can be used to explain the origin of the unfolded spectrum. The maximum photon energy extended to about 500 keV. The total photon production was 107/pulse. The FWHM source size was about 12 μm.

Human cystic echinococcosis (CE) is a zoonotic disorder triggered by the larval stage of Echinococcus granulosus (E. granulosus) and predominantly occurred in the liver and lungs. The M2 macrophage level is considerably elevated among the liver of patients with hepatic CE and performs an integral function in liver fibrosis. However, the mechanism of CE inducing polarisation of macrophage to an M2 phenotype is unknown. In this study, macrophage was treated with E. granulosus cyst fluid (EgCF) to explore the mechanism of macrophage polarisation. Consequently, the expression of the M2 macrophage and production of anti-inflammatory cytokines increased after 48 h treatment by EgCF. In addition, EgCF promoted polarisation of macrophage to an M2 phenotype by inhibiting the expression of transcriptional factor hypoxia-inducible factor 1-alpha (HIF-1α), which increased the expression of glycolysis-associated genes, including hexokinase 2 (HK2) and pyruvate kinase 2 (PKM2). The HIF-1α agonist ML228 also inhibited the induction of macrophage to an M2 phenotype by EgCF in vitro. Our findings indicate that E. granulosus inhibits glycolysis by suppressing the expression of HIF-1α.

Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.

This study presents a comprehensive analysis on the extreme positive and negative events of wall shear stress and heat flux fluctuations in compressible turbulent boundary layers (TBLs) solved by direct numerical simulations. To examine the compressibility effects, we focus on the extreme events in two representative cases, i.e. a supersonic TBL of Mach number $M=2$ and a hypersonic TBL of $M=8$, by scrutinizing the coherent structures and their correlated dynamics based on conditional analysis. As characterized by the spatial distribution of wall shear stress and heat flux, the extreme events are indicated to be closely related to the structural organization of wall streaks, in addition to the occurrence of the alternating positive and negative structures (APNSs) in the hypersonic TBL. These two types of coherent structures are strikingly different, namely the nature of wall streaks and APNSs are shown to be related to the solenoidal and dilatational fluid motions, respectively. Quantitative analysis using a volumetric conditional average is performed to identify and extract the coherent structures that directly account for the extreme events. It is found that in the supersonic TBL, the essential ingredients of the conditional field are hairpin-like vortices, whose combinations can induce wall streaks, whereas in the hypersonic TBL, the essential ingredients become hairpin-like vortices as well as near-wall APNSs. To quantify the momentum and energy transport mechanisms underlying the extreme events, we proposed a novel decomposition method for extreme skin friction and heat flux, based on the integral identities of conditionally averaged governing equations. Taking advantage of this decomposition method, the dominant transport mechanisms of the hairpin-like vortices and APNSs are revealed. Specifically, the momentum and energy transports undertaken by the hairpin-like vortices are attributed to multiple comparable mechanisms, whereas those by the APNSs are convection dominated. In that, the dominant transport mechanisms in extreme events between the supersonic and hypersonic TBLs are indicated to be totally different.

The penultimate deglaciation was characterized by a sub-millennial-scale warm event in the Heinrich Stadial 11(HS11), termed the 134-ka event. However, its precise timing and structure remain poorly constrained due to the lack of high-resolution and precisely dated records. We present an oxygen isotope record of a speleothem with well-developed annual lamina from Zhangjia Cave, located on the north margin of the Sichuan Basin, characterizing Asian summer monsoon (ASM) changes in the 134-ka event, which included an increase excursion of ca. 149 years and decrease excursion of ca. 200 years, inferred from 3.3‰ δ18O variations. This event also divided the weak ASM interval-II (WMI-II), corresponding to HS11, into two stages, the WMI-IIa 132.8–134.1 ka and WMI-IIb 134.4–136.4 ka. With a comparable climatic pattern globally, the 134-ka event is essentially similar to the millennial-scale events in last glacial–deglacial period. Particularly, the observed weak-strong-weak ASM sequence (138.8–132.8 ka) is largely controlled by changes in the Atlantic Meridional Overturning Circulation (AMOC) forced by the meltwater of northern high-latitude ice sheets. Moreover, our results underpin that AMOC, rather than the global ice volume, is more critical to ASM variations during the last two deglaciations.

Arising of disasters by climate change had affected crop growth and yield, and then threaten local to global food security, particularly heat stress. Therefore, hazard assessment is essential to develop effective disaster risk management and adaptation interventions to ensure food security. In this study, the accumulated heat stress days (DAY), heat stress intensity (HSI) and heat degree-days (HDD) during the post-silking period of summer maize in The Huang-Huai-Hai Plain were investigated. Based on the optimal probability distribution function of HDD and information diffusion theory, we compute heat stress classification index and the possibility of heat stress, respectively. During 1981–2019, DAY, HSI and HDD were 11.8 d, 31.9°C and 23.6°Cd and increased by 0.67 d/decade, 0.10°C/decade and 3.14°Cd/decade, respectively. The threshold and hazard probability of mild, moderate and severe heat stress were 9.4, 19.4 and 34.2°Cd and 16.6, 9.3 and 4.5%, respectively. The heat stress hazard index (M) was 0.48, ranged from 0 to 0.77 during 1981 to 2019. M will increase in the future at all regions, particularly after 2060. Under SSP5-8.5 climate scenario, M ranged from 0.95 to 1.20 in 2080s, about two times than historical period. This could be used in optimizing agricultural management in summer maize production in order to combat heat stress under projected climate change.

High-power femtosecond mid-infrared (MIR) lasers are of vast importance to both fundamental research and applications. We report a high-power femtosecond master oscillator power amplifier laser system consisting of a single-mode Er:ZBLAN fiber mode-locked oscillator and pre-amplifier followed by a large-mode-area Er:ZBLAN fiber main amplifier. The main amplifier is actively cooled and bidirectionally pumped at 976 nm, generating a slope efficiency of 26.9%. Pulses of 8.12 W, 148 fs at 2.8 μm with a repetition rate of 69.65 MHz are achieved. To the best of our knowledge, this is the highest average power ever achieved from a femtosecond MIR laser source. Such a compact ultrafast laser system is promising for a wide range of applications, such as medical surgery and material processing.

The resurgence and outbreaks of mumps occur frequently in many countries worldwide in recent years, even in countries with high vaccination coverage. In this study, a descriptive and spatiotemporal clustering analysis at the township level was conducted to explore the dynamic spatiotemporal aggregation and epidemiological characteristics of mumps in Wuhan. During 2005 and 2019, there were 40 685 cases reported in Wuhan, with an average annual morbidity of 28.11 per 100 000 populations. The morbidity showed a fluctuating tendency, and peaked in 2010 and 2018. Bimodal seasonality was found, with a large peak between May and July, and a mild peak from November to January in the following year. Male students aged 5–9-year-old were the main risk group of mumps infection. Significant global spatial auto-correlation was detected except in 2007, 2009 and 2015. The spatial and temporal scan statistics indicated that the hot-spots mainly located at the western and southern areas of Wuhan with variations almost every year. Our findings could assist the public health authorities to develop and improve targeted health strategies, and allocate health resources rationally.

We analyze a model in which an anomaly is unknown to arbitrageurs until its discovery, and test the model implications on both asset prices and arbitrageurs’ trading activities. Using data on 99 anomalies documented in the existing literature, we find that the discovery of an anomaly reduces the correlation between the returns of its decile-1 and decile-10 portfolios. This discovery effect is stronger if the aggregate wealth of hedge funds is more volatile. Finally, hedge funds increase (reverse) their positions in exploiting anomalies when their aggregate wealth increases (decreases), further suggesting that these discovery effects operate through arbitrage trading.

Transforming growth factor-beta (TGF-β) is a double-edged sword in cancer treatment because of its pivotal yet complex and roles played during cancer initiation/development. Current anti-cancer strategies involving TGF-β largely view TGF-β as an onco-therapeutic target that not only substantially hinders its full utilisation for cancer control, but also considerably restricts innovations in this field. Thereby, how to take advantages of therapeutically favourable properties of TGF-β for cancer management represents an interesting and less investigated problem. Here, by categorising cancer hallmarks into four critical transition events and one enabling characteristic controlling cancer initiation and progression, and delineating TGF-β complexities according to these cancer traits, we identify the suppressive role of TGF-β in tumour initiation and early-stage progression and its promotive functionalities in cancer metastasis as well as other cancer hallmarks. We also propose the feasibility and possible scenarios of combining cold atmospheric plasma (CAP) with onco-therapeutics utilising TGF-β for cancer control given the intrinsic properties of CAP against cancer hallmarks.

An experimental investigation of the stereocamera's systematic error is carried out to optimize three-dimensional (3-D) dust observation on the HL-2A tokamak. It is found that a larger 3-D region occupied by all calibration points is able to reduce the 3-D reconstruction systematic error of the stereocamera. In addition, the 3-D reconstruction is the most accurate around the region where the calibration points are located. Based on these experimental results, the design of the stereocamera on the HL-2A tokamak is presented, and a set of practical procedures to optimize the 3-D reconstruction accuracy of the stereocamera are proposed.

It has been suggested that added sugar intake is associated with non-alcoholic fatty liver disease (NAFLD). However, previous studies only focused on sugar-sweetened beverages; the evidence for associations with total added sugars and their sources is scarce. This study aimed to examine the associations of total added sugars, their physical forms (liquid v. solid) and food sources with risk of NAFLD among adults in Tianjin, China. We used data from 15 538 participants, free of NAFLD, other liver diseases, CVD, cancer or diabetes at baseline (2013–2018 years). Added sugar intake was estimated from a validated 100-item FFQ. NAFLD was diagnosed by ultrasonography after exclusion of other causes of liver diseases. Multivariable Cox proportional hazards models were fitted to calculate hazard ratios (HR) and corresponding 95 % CI for NAFLD risk with added sugar intake. During a median follow-up of 4·2 years, 3476 incident NAFLD cases were documented. After adjusting for age, sex, BMI and its change from baseline to follow-up, lifestyle factors, personal and family medical history and overall diet quality, the multivariable HR of NAFLD risk were 1·18 (95 % CI 1·06, 1·32) for total added sugars, 1·20 (95 % CI 1·08, 1·33) for liquid added sugars and 0·96 (95 % CI 0·86, 1·07) for solid added sugars when comparing the highest quartiles of intake with the lowest quartiles of intake. In this prospective cohort of Chinese adults, higher intakes of total added sugars and liquid added sugars, but not solid added sugars, were associated with a higher risk of NAFLD.

Spectral observations with high temporal and frequency resolution are of great significance for studying the fine structures of solar radio bursts. In addition, it is helpful to understand the physical processes of solar eruptions. In this paper, we present the design of a system to observe solar radio bursts with high temporal and frequency resolutions at frequencies of 25–110 MHz. To reduce the impact of analog devices and improve the system flexibility, we employ various digital signal processing methods to achieve the function of analog devices, such as polarisation synthesis and beamforming. The resourceful field programmable gate array is used to process radio signals. The system has a frequency resolution of $\sim$ 30 kHz and a temporal resolution of up to 0.2 ms. The left/right circular polarisation signals can be simultaneously observed. At present, the system has been installed at Chashan Solar Observatory operated by the Institute of Space Science, Shandong University. The system is running well, multiple bursts have been observed, and relevant data have been obtained.

We present an experimental and numerical study of turbulent thermal convection in the presence of an effective horizontal buoyancy that generates extra shear at the boundary. Geometrical confinements are also applied by varying the streamwise and spanwise aspect ratios of the convection cell to condense the plumes. With these, we systematically explore the effects of plume and shear on heat transfer. It is found that a streamwise confinement results in increased plume coverage but decreased shear compared with spanwise confinement. The fact that streamwise confinement leads to a higher vertical heat transfer efficiency than the spanwise confined case suggests that the increase of plume coverage is the dominant effect responsible for the enhanced heat transfer. Our results highlight the potential applications of coherent structure manipulation in efficient passive heat transfer control and thermal engineering. We also analyse the energetics of the present system and derive the expression of mixing efficiency accordingly. The mixing efficiency is found to increase with both the buoyancy ratio and streamwise dimension.