Sarcopenic obesity is regarded as a risk factor for the progression and development of non-alcoholic fatty liver disease (NAFLD). Since male sex is a risk factor for NAFLD and skeletal muscle mass markedly varies between the sexes, we examined whether sex influences the association between appendicular skeletal muscle mass to visceral fat area ratio (SVR), that is, an index of skeletal muscle mass combined with abdominal obesity, and the histological severity of NAFLD. The SVR was measured by bioelectrical impedance in a cohort of 613 (M/F = 443/170) Chinese middle-aged individuals with biopsy-proven NAFLD. Multivariable logistic regression and subgroup analyses were used to test the association between SVR and the severity of NAFLD (i.e. non-alcoholic steatohepatitis (NASH) or NASH with the presence of any stage of liver fibrosis). NASH was identified by a NAFLD activity score ≥5, with a minimum score of 1 for each of its categories. The presence of fibrosis was classified as having a histological stage ≥1. The SVR was inversely associated with NASH in men (adjusted OR 0·62; 95 % CI 0·42, 0·92, P = 0·017 for NASH, adjusted OR 0·65; 95 % CI 0·43, 0·99, P = 0·043 for NASH with the presence of fibrosis), but not in women (1·47 (95 % CI 0·76, 2·83), P = 0·25 for NASH, and 1·45 (95 % CI 0·74, 2·83), P = 0·28 for NASH with the presence of fibrosis). There was a significant interaction for sex and SVR (P interaction = 0·017 for NASH and P interaction = 0·033 for NASH with the presence of fibrosis). Our findings show that lower skeletal muscle mass combined with abdominal obesity is strongly associated with the presence of NASH only in men.

The present study investigated the effects of exposure to Chinese orthography on learning phonological forms of new words in learners of Chinese as a second language. A total of 30 adult learners of Chinese studied spoken label and picture associations presented either with phonologically accurate characters, characters with partial phonological information, or no orthography. Half the phonologically accurate or partially accurate characters were semantically transparent or opaque. Spoken labels were recalled without orthography presence. Results showed that exposure to phonologically accurate and semantically transparent characters during learning did not enhance the recall of the spoken labels compared to no orthography. But exposure to characters with partial phonological information and semantically opaque characters significantly hindered vocabulary learning. The implications for Chinese as a second language vocabulary acquisition and instruction are discussed.

Seasonal climate variability is an important component of Earth's climate system, and has a significant impact on ecosystems and social systems. However, the temporal resolution of most proxy-based paleoclimate records is limiting to fully understand the past seasonal changes. Here, we used high-precision monthly resolution Sr/Ca records of three Tridacna squamosa specimens from the northern South China Sea (SCS) to reconstruct the sea surface temperature (SST) seasonality during three time periods from the middle Holocene. The results suggested that SST seasonality in the northern SCS during the middle Holocene (3.21 ± 0.98°C) was smaller than that for recent decades (AD 1994–2004, 4.32 ± 0.59°C). Analysis of modern instrumental data showed that the SST seasonality in the northern SCS was dominated by the winter SST, which was deeply influenced by the intensity of East Asian winter monsoon (EAWM). A strong EAWM usually resulted in cooler winter SST and a larger SST seasonality in the northern SCS. The reconstructed Holocene EAWM records showed that the EAWM strengthened from the middle to late Holocene, which was seen in our reconstruction of less SST seasonality changes during the middle Holocene in the northern SCS. This study highlighted that the Sr/Ca ratios from Tridacna shells can be used as a potential high-resolution indicator of past seasonal climate changes.

Echinococcus shiquicus is currently limited to the Qinghai–Tibet plateau, a large mountainous region in China. Although the zoonotic potential remains unknown, progress is being made on the distribution and intermediate host range. In this study, we report E. shiquicus within Gansu and Qinghai provinces in regions located not only around the central areas but also the southeast edge of the plateau and describe their genetic relationship with previous isolates from the plateau. From 1879 plateau pikas examined, 2.39% (95% CI 1.79–3.18) were infected with E. shiquicus. The highest prevalence of 10.26% (4.06–23.58) was recorded in Makehe town, Qinghai province. Overall the prevalence was marginally higher in Qinghai (2.5%, CI 1.82–3.43) than in Gansu (2%, CI 1.02–3.89). The cox1 and nad1 genes demonstrated high and low haplotype and nucleotide diversities, respectively. The median-joining network constructed by the cox1–nad1 gene sequences demonstrated a star-like configuration with a median vector (unsampled haplotype) occupying the centre of the network. No peculiar distinction or common haplotype was observed in isolates originating from the different provinces. The presence of E. shiquicus in regions of the southeast and northeast edges of the Qinghai–Tibet plateau and high genetic variation warrants more investigation into the haplotype distribution and genetic polymorphism by exploring more informative DNA regions of the mitochondrial genome to provide epidemiologically useful insight into the population structure of E. shiquicus across the plateau and its axis.

Steam jet milling was applied for the first time to ultra-fine grind the filter cake (moisture content 23.80%) produced by a kaolin concentrator. The material was dehydrated and dried simultaneously during grinding, and the final ground sample met the moisture content requirement for powder products of <2%. The particle size of the ground kaolin samples decreased and the particle-size distribution was more concentrated, indicating that the steam jet milling was more effective for kaolin processing than the conventional dry grinding process. In addition, steam jet milling can improve the whiteness and decrease the crystal order of the samples, thus improving the kaolin properties in follow-up applications.

ABSTRACT IMPACT: Triple negative breast cancer (TNBC) affects 10-20% of women with breast cancer and is biologically more aggressive than other subtypes. The novel compound we have developed, DL7076, would give clinicians a vital strategy to improve the commonly used cyclophosphamide (CPA) and doxorubicin (DOX) regimen in the treatment of TNBC. OBJECTIVES/GOALS: The objective of this research project is to develop a novel compound which can activate both 1) the constitutive androstane receptor (CAR) and subsequently enhance the CYP2B6-mediated activation of CPA, and 2) the nuclear factor erythroid- related factor-2 (Nrf2) leading to the cardiomyocyte protection from DOX-associated cardiotoxicity. METHODS/STUDY POPULATION: Following the identification of the compound candidate, DL7076 was evaluated for tissue specific induction of CAR and Nrf2 using qPCR, western blot analysis, and luciferase reporter assays.

Further, we have developed a multicellular coculture model incorporating human primary hepatocytes for metabolism, TNBC spheroids as the target, and cardiomyocytes as a side target of DOX. We have investigated the anticancer effects of CPA/DOX on TNBC cells and the toxic effects on cardiomyocytes with/without a CAR-Nrf2 activator, in a multicellular environment where hepatic metabolism is well-retained. RESULTS/ANTICIPATED RESULTS: We found that our dual activator of CAR and Nrf2, DL7076, exhibits tissue specific induction of CAR and Nrf2. Inclusion of DL7076 in combination with the CPA/DOX regimen improves anticancer efficacy, through the subsequent increase in the formation of the active CPA metabolite. With the addition of DL7076, DOX-mediated off-target cardiotoxicity was markedly reduced.

Lastly, utilizing the novel coculture system with human primary hepatocytes, TNBC spheroids, and cardiomyocytes, the inclusion of DL7076 to the CPA/DOX regimen shows decreased spheroid viability and improved cardiomyocyte viability and function. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that DL7076 can facilitate DOX/CPA containing regimens by increasing CAR-mediated metabolism and subsequent CPA bioactivation while selectively protecting cardiomyocytes from DOX-induced toxicity. This research is expected to translate our basic scientific findings into therapeutic interventions for women with TNBC.

This study aimed to evaluate to what extent the different interval times between trophectoderm (TE) biopsy and vitrification influence the clinical outcomes in preimplantation genetic testing (PGT) cycles. Patients who underwent frozen embryo transfer (FET) after PGT between 2015 and 2019 were recruited. In total, 297 cycles with single day 5 euploid blastocyst transfer were included. These cycles were divided into three groups according to the interval times: <1 h group, 1–2 h group, and ≥2 h group. Blastocyst survival, clinical pregnancy, miscarriage, and ongoing pregnancy rates were compared. The results showed that, in PGT-SR cycles, survival rate in the ≥2 h group (96.72%) was significantly lower than in the <1 h group (100%, P = 0.047). The clinical pregnancy rate in the ≥2 h group was 55.93%, significantly lower than in the <1 h group (74.26%, P = 0.017). The ongoing pregnancy rates in the 1–2 h group and the ≥2 h group were 48.28% and 47.46%, respectively, significantly lower than that in the <1 h group (67.33%, P < 0.05). The miscarriage rate in the 1–2 h group was 18.42%, significantly higher than that in the <1 h group (5.33%, P = 0.027). In PGT-A cycles, the clinical pregnancy and ongoing pregnancy rates in the <1 h group were 67.44% and 53.49%, respectively, higher than that in the 1–2 h group (52.94%, 47.06%, P > 0.05) and the ≥2 h group (52.63%, 36.84%, P > 0.05). In conclusion, vitrification of blastocysts beyond 1 h after biopsy significantly influences embryo survival and clinical outcomes and is therefore not recommended.

The effect of turbulence on snow precipitation is not incorporated into present weather forecasting models. Here we show evidence that turbulence is in fact a key influence on both fall speed and spatial distribution of settling snow. We consider three snowfall events under vastly different levels of atmospheric turbulence. We characterize the size and morphology of the snow particles, and we simultaneously image their velocity, acceleration and relative concentration over vertical planes approximately $30\ \textrm {m}^2$ in area. We find that turbulence-driven settling enhancement explains otherwise contradictory trends between the particle size and velocity. The estimates of the Stokes number and the correlation between vertical velocity and local concentration are consistent with the view that the enhanced settling is rooted in the preferential sweeping mechanism. When the snow vertical velocity is large compared to the characteristic turbulence velocity, the crossing trajectories effect results in strong accelerations. When the conditions of preferential sweeping are met, the concentration field is highly non-uniform and clustering appears over a wide range of scales. These clusters, identified for the first time in a naturally occurring flow, display the signature features seen in canonical settings: power-law size distribution, fractal-like shape, vertical elongation and large fall speed that increases with the cluster size. These findings demonstrate that the fundamental phenomenology of particle-laden turbulence can be leveraged towards a better predictive understanding of snow precipitation and ground snow accumulation. They also demonstrate how environmental flows can be used to investigate dispersed multiphase flows at Reynolds numbers not accessible in laboratory experiments or numerical simulations.

In glaciology, snow–firn temperature at 10 m is considered a representation of the mean annual air temperature at the surface (MAAT) of the studied site. Although MAAT is an important parameter in ice-sheet investigations, it has not been widely measured in Antarctica. To measure the 10 m snow–firn temperature in Antarctica, a shallow hot-point drill system is designed. In this simple and lightweight system, a hot-point drill can melt boreholes with a diameter of 34 mm in the snow–firn to a depth of 30 m and a temperature sensors string can measure the borehole temperature precisely. In the 2018/19 field season, 16 boreholes along the Zhongshan–Dome A traverse were drilled, and the borehole temperature was measured. Although certain problems existed pertaining to the hot-point drill, a total depth of ~244 m was successfully drilled at an average penetration rate of ~10 m h−1. After borehole drilling, ~12–15 h were generally required for the borehole to achieve thermal equilibrium with the surroundings. Preliminary results demonstrated that the 10 m snow–firn temperature along the traverse route was affected by the increasing altitude and latitude, and it decreased gradually with an increase in the distance from Zhongshan station.

A study was conducted to identify whether composted manure and straw amendments (replacement of a portion of chemical fertilizer [50% of the total nitrogen application] with composted pig manure, and straw return [all straw from the previous rice crop] combined with chemical fertilizer) compared with no fertilization and chemical fertilizer only would change the dominant species of wheat-associated weeds as well as influence their growth and seed yield in a rice (Oryza sativa L.)–wheat (Triticum aestivum L.) rotation system. The study was initiated in 2010, and the treatment effects on the species, density, plant height, shoot biomass, seed yield of dominant weeds, and wheat yields were assessed in 2017 and 2018. Fertilization significantly increased the height, density, and yield of wheat, as well as the shoot biomass of wheat-associated weeds, but decreased the weed species number. A total of 17 and 14 weed species were recorded in the experimental wheat fields in 2017 and 2018, respectively. The most dominant weed species were American sloughgrass [Beckmannia syzigachne (Steud.) Fernald] and catchweed bedstraw (Galium aparine L.), which made up more than 64% of the weed community in all treatments. When the chemical fertilizer application was amended with pig manure compost and straw return, the relative abundance of B. syzigachne significantly decreased, while the relative abundance of G. aparine significantly increased. The application of the chemical fertilizer-only treatment resulted in increases in the density, shoot biomass, and seed yield of B. syzigachne, while the composted manure and straw amendments applied together with chemical fertilizer led to significant increases in the density, shoot biomass, and seed yield of G. aparine. Consequently, further research on ways to promote greater cropping system diversity will be needed to prevent the selection of weed species that are adapted to a limited suite of crop management practices.

Hypertension represents one of the most common pre-existing conditions and comorbidities in Coronavirus disease 2019 (COVID-19) patients. To explore whether hypertension serves as a risk factor for disease severity, a multi-centre, retrospective study was conducted in COVID-19 patients. A total of 498 consecutively hospitalised patients with lab-confirmed COVID-19 in China were enrolled in this cohort. Using logistic regression, we assessed the association between hypertension and the likelihood of severe illness with adjustment for confounders. We observed that more than 16% of the enrolled patients exhibited pre-existing hypertension on admission. More severe COVID-19 cases occurred in individuals with hypertension than those without hypertension (21% vs. 10%, P = 0.007). Hypertension associated with the increased risk of severe illness, which was not modified by other demographic factors, such as age, sex, hospital geological location and blood pressure levels on admission. More attention and treatment should be offered to patients with underlying hypertension, who usually are older, have more comorbidities and more susceptible to cardiac complications.

Microglia, the main immune cell of the central nervous system (CNS), categorized into M1-like phenotype and M2-like phenotype, play important roles in phagocytosis, cell migration, antigen presentation, and cytokine production. As a part of CNS, retinal microglial cells (RMC) play an important role in retinal diseases. Diabetic retinopathy (DR) is one of the most common complications of diabetes. Recent studies have demonstrated that DR is not only a microvascular disease but also retinal neurodegeneration. RMC was regarded as a central role in neurodegeneration and neuroinflammation. Therefore, in this review, we will discuss RMC polarization and its possible regulatory factors in early DR, which will provide new targets and insights for early intervention of DR.

Laboratory experiments are conducted to investigate the mechanism controlling the formation of stable and unstable acoustic fountains at the free surface of a quiescent body of water. Fountains are induced by focused ultrasonic, a new modality that allows for better spatiotemporal control of water flow. Particle image velocimetry was used to characterize the induced flow field in the vicinity of the ultrasonic focal spot. We used two types of ultrasonic transducers with distinct wave frequencies. We examined three fountain formation regimes by varying the pressure level of the transducers, namely weak, intermediate (stable) and highly forced fountains (explosive). Between different regimes, the fountain height underwent a step-change in response to the increase in acoustic pressure. A force estimation obtained from the flow field shows that the magnitude of axial momentum flux is orders of magnitude lower than that of gravity and surface tension, indicating that the dominant driving force for the fountain generation is the acoustic radiation force (Nightingale et al., Ultrasound Med. Biol., vol. 28, 2002, pp. 227–235). We propose a simple model to estimate the shape of a stable fountain; it accounts for the applied acoustic pressure, gravity, surface tension and axial momentum. The model neglects viscous force, which precludes capturing the intermediate fountain surface curvature. However, the model successfully predicts the geometry of the weak and intermediate fountains.