The results of this study indicate that oat β-glucan inhibits HFD-induced hyperlipidemia in mice and lipid accumulation in the oleic acid-induced HepG2 cells. Oat β-glucan exerts its anti-lipid ...effect by modifying lipid metabolism-related genes and AMPK activation is the key effector in the process.
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•Lipid-lowering effect of oat β-glucan in high-fat diet (HFD)-induced mice was studied.•Oat β-glucan inhibits FAS and SREBP-1 expressions and activates AMPK in liver and fat tissues.•Oat β-glucan prevents OA-induced lipid accumulation in HepG2 cells.•Oat β-glucan inhibiting OA-induced lipid accumulation is related with activation of AMPK signal.•Oat β-glucan regulates downstream target genes of AMPK and modifies lipid metabolism in OA-induced lipid accumulation model.
To evaluate the lowering-lipid effect of oat β-glucan (OβG) and its molecular mechanism, high-fat diet (HFD)-induced hyperlipidemic mouse model and oleic acid-induced lipid accumulation model of HepG2 cells were used in this study. OβG obviously reduced HFD-induced the gain of body weight and epididymal fat pad, and inhibited hepatic adipocyte hyperplasia. These effects were associated with the down-regulation of FAS and SREBP-1, up-regulation of PPARα and particularly the activation of AMP-activated protein kinase (AMPK) signaling in both liver and fat tissues. In the oleic acid-induced HepG2 cells, OβG partly suppressed lipogenesis and activated AMPK. OβG inhibited lipid metabolism-related protein expressions such as FAS, SREBP-1, CPT-1, PPARα and activating ACC, which are the downstream targets of AMPK. Taken together, our results suggest that administration of OβG exerts lipid-lowering effect in HFD mice via AMPK signal pathway, which provide novel application for the prevention and treatment of hyperlipidemia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Antibiotics and microplastics (MPs) have become critical concerns worldwide because of their increasing amount and ecological risks to ecosystems. However, how MPs exposure affects the ...bioaccumulation and risks of antibiotics in waterfowls remains poorly understood. In this study, Muscovy ducks were exposed to single and combined contamination with polystyrene MPs and chlortetracycline (CTC) for 56 days, and the effects of MPs on CTC bioaccumulation and their risks in duck intestines were investigated. MPs exposure reduced the bioaccumulation of CTC in the intestine and liver of ducks and increased their fecal CTC excretion. MPs exposure caused severe oxidative stress, inflammatory response, and intestinal barrier damages. Microbiome analysis showed that MPs exposure induced microbiota dysbiosis by increasing the abundance of Streptococcus and Helicobacter, the increase of which may exacerbate intestinal damages. Co-exposure to MPs and CTC alleviated the intestinal damage by regulating the gut microbiome. Metagenomic sequencing revealed that the combined exposure to MPs and CTC increased the abundance of Prevotella, Faecalibacterium, and Megamonas and incidence of total antibiotic resistance genes (ARGs), especially tetracycline ARGs subtypes in the gut microbiota. The results obtained herein provide new insights into the potential risks of polystyrene MPs and antibiotics in waterfowls living in aquatic environments.
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•The health risks of ducks co-exposed to MPs and CTC were firstly evaluated.•MPs exposure induced oxidative stress, inflammation and microbiota dysbiosis.•MPs exposure altered the intestinal microbiota composition and structure.•MPs co-exposure with CTC alleviate the intestinal damage induced by MPs.•MPs and CTC co-exposure significantly increased the relative abundances of ARGs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Electron transport materials (ETM) play an important role in the improvement of efficiency and stability for inverted perovskite solar cells (PSCs). This work reports an efficient ETM, named PDI‐C60, ...by the combination of perylene diimide (PDI) and fullerene. Compared to the traditional PCBM, this strategy endows PDI‐C60 with slightly shallower energy level and higher electron mobility. As a result, the device based on PDI‐C60 as electron transport layer (ETL) achieves high power conversion efficiency (PCE) of 18.6 %, which is significantly higher than those of the control devices of PCBM (16.6 %) and PDI (13.8 %). The high PCE of the PDI‐C60‐based device can be attributed to the more matching energy level with the perovskite, more efficient charge extraction, transport, and reduced recombination rate. To the best of our knowledge, the PCE of 18.6 % is the highest value in the PSCs using PDI derivatives as ETLs. Moreover, the device with PDI‐C60 as ETL exhibits better device stability due to the stronger hydrophobic properties of PDI‐C60. The strategy using the PDI/fullerene hybrid provides insights for future molecular design of the efficient ETM for the inverted PSCs.
The combination of perylene diimide and fullerene results in a new hybrid as electron transporting material (ETM) in inverted perovskite solar cells. This hybrid ETM enables a high power conversion efficiency of 18.6 % and good device stability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To improve independent innovation ability, China has explored a unique form of R&D organization called the New R&D Institute (NRDI). The spillover effect of NRDIs in the region arouses curiosity ...about what exactly drives its innovation performance. After clarifying the NRDI concept and its characteristics, this study studies Nanjing, a typical city with the rapid development of NRDIs in China, to empirically explore the impact mechanism of NRDI development in their start‐up period. The study uses panel data from 103 NRDIs spanning 10 quarters from the third quarter of 2018 to the fourth quarter of 2020. Our analysis reveals that R&D investment, government support, research infrastructure, and angel investment have mixed impacts on the revenue, innovation, and enterprise incubation of NRDIs. Specifically, resource inputs such as R&D staff, R&D service platforms, and R&D expenditures boost the revenue growth of NRDIs. In contrast, only a few inputs play an important role in NRDIs’ innovation and enterprise incubation, including service platforms, capital investment from high‐tech parks, and angel funding. The early development of NRDIs has four features. (1) It is driven more by material capital (R&D expenditure) than by human capital (R&D staff). (2) It relies more on government support rather than institution investment. (3) Research infrastructure has specific significant effects on the innovative output of NRDIs. (4) Angel investment is critical to promote technological innovation and business incubation. Most of the input elements have not yet been very effective in the innovation and incubation of NRDIs. Our research offers essential insights for understanding the innovation mechanism in NRDIs and promoting their healthy development.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The consensus problem of nonlinear multi‐agent systems with nonuniform time‐varying connection topologies via two novel distributed hybrid control protocols is discussed. By using the degrees of ...freedom brought by coupling weights, impulsive control with impulse time windows integrates intermittent control and impulsive control into a unified control framework and is more suitable for the situations where only the time intervals in which impulses occur are known but the exact instants of impulses cannot be identified. Compared with intermittent control, the intermittent impulsive control (IIC) reduces the amount of data transmission and improves the security of the system. The introduction of the rest windows makes the IIC break the limit of the upper bound of impulsive intervals of general impulsive control, and the system is easier to maintain according to plan. Control‐time‐dependent Lyapunov function based methods are developed to overcome the difficulty of stability analysis of the error systems caused by continuous switching of multiple dynamic subsystems. Two consensus criteria are presented and the corresponding controller design schemes are proposed. The results can uniformly deal with the positive and negative effects of impulses, and do not require at least one subsystem of the error system to be stable. Three examples are given to demonstrate the effectiveness of the derived theoretical results.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Breastfeeding education plays a crucial role in improving breastfeeding outcomes and has been employed in many medical institutions across China.
To describe the current situation of breastfeeding ...education provided by hospitals to women in China, and to identify relevant factors associated with the exclusive breastfeeding rate at hospital discharge and the early breastfeeding initiation rate.
A cross-sectional study design.
We used an online survey platform called WenjuanXing to collect data from 2985 hospitals in China.
We designed a questionnaire to collect data. The Mann–Whitney U test and Pearson's chi-square test were used to identify the differences between the different types and levels of hospitals. Binary logistic regression analysis was used to analyze the factors associated with the exclusive breastfeeding rate at hospital discharge and the early breastfeeding initiation rate.
A total of 2941 hospitals were included in the data analysis. In 86% of hospitals midwives were providing breastfeeding education on weekdays during the daytime. Information on how to deal with mastitis (80.8%) and weaning methods (71.5%) was less commonly provided to women. The hospitals often conducted breastfeeding education through antenatal education sessions and bedside health education, while 34.2% of hospitals used smartphone applications. The obstacles to conducting breastfeeding education in hospitals were a lack of full-time staff dedicated to breastfeeding education (43.3%) and limited funds invested in breastfeeding education (42.5%). A lack of full-time staff dedicated to breastfeeding education (OR, 0.689; 95% CI, 0.498–0.953) and a lack of space (OR, 0.697; 95% CI, 0.487–0.997) were associated with the exclusive breastfeeding rate at hospital discharge. Furthermore, a lack of full-time staff dedicated to breastfeeding education (OR, 0.372; 95% CI, 0.235–0.589) was associated with the early breastfeeding initiation rate.
To improve breastfeeding outcomes, hospital managers and policymakers should increase the number of midwives and full-time staff who are dedicated to breastfeeding education, resolve the obstacles of limited funds and space for breastfeeding education, and explore more approaches to providing knowledge on breastfeeding to women and their families.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The COF@CNT composites exhibit excellent long-term cycling stability as sulfur carriers with an average Coulombic efficiency of 99.7% over 1000 cycles at 1 C.
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•A COF@CNT composite ...sulfur carrier was prepared based on benzothiadiazole-based COF and CNT.•The COF@CNT composite has excellent electrical conductivity.•The heteroatom on COF has adsorption and catalytic functions for polysulfides.•The composite electrode showed 0.029% attenuation per cycle with Coulombic efficiency of 99.7%.
The cycle stability and dynamic performance of lithium-sulfur (Li-S) batteries have been major challenges, which primarily arise from the dissolution and migration of the soluble reaction intermediates during cycling, as well as the low conductivity of sulfur. In this study, a covalent organic framework containing heteroatoms (B/N/S) is uniformly wrapped on the outer surface of carbon nanotubes to form a nanocomposite (COF@CNT). The composite combines the excellent electrical conductivity of CNTs and the COF material containing evenly distributed heteroatoms that can adsorb and catalyze polysulfides. B atom on COF can be chemically adsorbed by the negatively charged SX2−, S and N atoms can interact with Li+ to reduce the “shuttle effect”. At the same time, the heteroatoms promote the liquid-to-solid phase conversion of the soluble long-chain Li2Sx (4 ≤ x ≤ 8), and the subsequent conversion of solid Li2S2 to Li2S, thereby enhancing the dynamic kinetics. As a cathode material, COF@CNT/S exhibits an initial specific capacity of 1176 mAh/g at 0.2 C, maintaining a capacity of 688 mAh/g after 1000 cycles at 1 C with a Coulombic efficiency of 99.7 %. Notably, a quite low capacity decay rate of 0.029 % per cycle has been achieved, making the COF@CNT/S cathode one of the most stable electrode material for Li-S batteries. This work provides insights into improving cycle performance of Li-S batteries, and also enriches the current study on host materials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aquatic environment is an important medium for the accumulation and dissemination of antibiotic-resistant bacteria as it is often closely related to human activities. Previous studies paid little ...attention to the prevalence and mechanism of polymyxin-resistant bacteria in the aquatic environment. As a Gram-negative opportunistic pathogen widely distributed in aquatic ecosystems, the antibiotic-resistant profile of
Aeromonas
spp. deserves much attention. In this study, we identified 61
Aeromonas
spp. isolates from water samples in the section of the Yangtze River. The total polymyxin B (PMB) resistance rate of these strains was 49.18% (30/61), showing a high level of polymyxin resistance in
Aeromonas
spp. The MIC
50
and MIC
90
for PMB exhibited a significant discrepancy among different species (
p
< 0.001). The MIC
50
and MIC
90
for PMB in the
Aeromonas hydrophila
were 128 mg/L and above 128 mg/L while in
Aeromonas caviae
and
Aeromonas veronii
, the MIC
50
and MIC
90
value were both 2 mg/L. Only two
A
.
veronii
strains (MIC = 2 mg/L) and one
A
.
caviae
strain (MIC = 0.5 mg/L) were identified as carrying mobilized polymyxin resistant gene
mcr-3
.
42
, and
mcr-3
.
16
. All
mcr
genes were located in the chromosome. This is the first report that the downstream region of
mcr
-3.42 was the truncated
mcr-3
-like gene separated by the insertion sequences of IS
As20
(1,674 bp) and IS
As2
(1,084 bp). Analysis of epidemiology of
mcr
-positive
Aeromonas
genomes from GenBank database showed that the genus
Aeromonas
and the aquatic environment might be the potential container and reservoir of
mcr-3
. By the whole-genome sequencing and qRT-PCR, we inferred that the sequence differences in the AAA domain of MlaF protein and its expression level among these three species might be involved in the development of polymyxin resistance. Our study provided evidences of the possible mechanism for the variety of polymyxin susceptibility in different species of the genus
Aeromonas
and a theoretical basis for the surveillance of the aquatic environment.
The wide spread of plasmid-borne mobilized colistin resistance (
) genes from animals to humans broadly challenges the clinical use of polymyxins. Here, we evaluated the incidence of a recently ...reported
variant,
-
, in animals and humans in the same area. Our results revealed the presence of novel
-carrying plasmids in two Klebsiella pneumoniae isolates from chickens, one Escherichia coli isolate from slaughterhouse workers, and a chromosome-borne
gene in Enterobacter kobei from a healthy resident in the same region. It is worth mentioning that the multidrug-resistant ST11 K. pneumoniae isolates coharboring
-
and
genes in two separate plasmids not only were resistant to polymyxins (MIC = 8 mg/L) but also showed reduced susceptibility to tigecycline (MIC ≥ 2 mg/L) due to the
(A) mutation or the
gene cluster. The structure
-
-
-like was found in genetic environments of both the plasmid and chromosome carrying
. We compared genomic epidemiological characteristics of
-harboring bacteria available in 941,449 genomes in the NCBI database (including strains of K. pneumoniae, E. coli, and
) with isolates in this study. The results indicated a sporadic distribution of
all around the world and in a variety of sources, including humans, environments, and animals, which confirms that
has spread among various hosts and warrants close monitoring and further future studies.
We discovered
-harboring isolates in the "one health" approach and reported for the first time multidrug-resistant clinically threatening ST11 K. pneumoniae isolates coharboring
-
and
genes that are resistant to polymyxins and show reduced susceptibility to tigecycline. The exhaustive screening of 941,449 bacterial genomes in the GenBank database discovered a sporadic distribution of
-harboring isolates all around the world in a variety of sources, especially humans, which warrants close monitoring and a particular concern in clinical settings.
Abstract
Background
Dual inhibition of PD-1/PD-L1 and TGF-β pathways is a rational therapeutic strategy for malignancies. SHR-1701 is a new bifunctional fusion protein composed of a monoclonal ...antibody against PD-L1 fused with the extracellular domain of TGF-β receptor II. This first-in-human trial aimed to assess SHR-1701 in pretreated advanced solid tumors and find the population who could benefit from SHR-1701.
Methods
This was a dose-escalation, dose-expansion, and clinical-expansion phase 1 study. Dose escalation was initiated by accelerated titration (1 mg/kg q3w; intravenous infusion) and then switched to a 3+3 scheme (3, 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w), followed by dose expansion at 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w. The primary endpoints of the dose-escalation and dose-expansion parts were the maximum tolerated dose and recommended phase 2 dose. In the clinical-expansion part, selected tumors were enrolled to receive SHR-1701 at the recommended dose, with a primary endpoint of confirmed objective response rate (ORR).
Results
In total, 171 patients were enrolled (dose-escalation:
n
=17; dose-expansion,
n
=33; clinical-expansion,
n
=121). In the dose-escalation part, no dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. SHR-1701 showed a linear dose-exposure relationship and the highest ORR at 30 mg/kg every 3 weeks, without obviously aggravated toxicities across doses in the dose-escalation and dose-expansion parts. Combined, 30 mg/kg every 3 weeks was determined as the recommended phase 2 dose. In the clinical-expansion part, SHR-1701 showed the most favorable efficacy in the gastric cancer cohort, with an ORR of 20.0% (7/35; 95% CI, 8.4–36.9) and a 12-month overall survival rate of 54.5% (95% CI, 29.5–73.9). Grade ≥3 treatment-related adverse events occurred in 37 of 171 patients (22%), mainly including increased gamma-glutamyltransferase (4%), increased aspartate aminotransferase (3%), anemia (3%), hyponatremia (3%), and rash (2%). Generally, patients with PD-L1 CPS ≥1 or pSMAD2 histochemical score ≥235 had numerically higher ORR.
Conclusions
SHR-1701 showed an acceptable safety profile and encouraging antitumor activity in pretreated advanced solid tumors, especially in gastric cancer, establishing the foundation for further exploration.
Trial registration
ClinicalTrials.gov
, NCT03710265
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
