Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke

In recent years, the frequency of strokes has been on the rise year by year and has become the second leading cause of death around the world, which is characterized by a high mortality rate, high recurrence rate, and high disability rate. Ischemic strokes account for a large percentage of strokes. A reperfusion injury in ischemic strokes is a complex cascade of oxidative stress, neuroinflammation, immune infiltration, and mitochondrial damage. Conventional treatments are ineffective, and the presence of the blood-brain barrier (BBB) leads to inefficient drug delivery utilization, so researchers are turning their attention to nano-drug delivery systems. Functionalized nano-drug delivery systems have been widely studied and applied to the study of cerebral ischemic diseases due to their favorable biocompatibility, high efficiency, strong specificity, and specific targeting ability. In this paper, we briefly describe the pathological process of reperfusion injuries in strokes and focus on the therapeutic research progress of nano-drug delivery systems in ischemic strokes, aiming to provide certain references to understand the progress of research on nano-drug delivery systems (NDDSs)

Bacteria Synergized with PD-1 Blockade Enhance Positive Feedback Loop of Cancer Cells-M1 Macrophages-T Cells in Glioma

Cancer immunotherapy is an attractive strategy because it stimulates immune cells to target malignant cells by regulating the intrinsic activity of the immune system. However, due to lacking many immunologic markers, it remains difficult to treat glioma, a representative cold tumor. Herein, to wake the hot tumor immunity of glioma, Porphyromonas gingivalis (Pg) is customized with a coating to create an immunogenic tumor microenvironment and further prove the effect in combination with the immune checkpoint agent anti-PD-1, exhibiting elevated therapeutic efficacy. This is accomplished not by enhancing the delivery of PD-1 blockade to enhance the effect of immunotherapy, but by introducing bacterial photothermal therapy to promote greater involvement of M1 cells in the immune response. After reaching glioma, the bacteria further target glioma cells and M2 phenotype macrophages selectively, enabling precise photothermal conversion for lysing tumor cells and M2 phenotype macrophages, which thereby enhances the positive feedback loop of cancer cells-M1 macrophages-T cells. Collectively, the bacteria synergized with PD-1 blockade strategy may be the key to overcoming the immunosuppressive glioma microenvironment and improving the outcome of immunotherapy toward glioma

Reasoning over Hierarchical Question Decomposition Tree for Explainable Question Answering

Explainable question answering (XQA) aims to answer a given question and provide an explanation why the answer is selected. Existing XQA methods focus on reasoning on a single knowledge source, e.g., structured knowledge bases, unstructured corpora, etc. However, integrating information from heterogeneous knowledge sources is essential to answer complex questions. In this paper, we propose to leverage question decomposing for heterogeneous knowledge integration, by breaking down a complex question into simpler ones, and selecting the appropriate knowledge source for each sub-question. To facilitate reasoning, we propose a novel two-stage XQA framework, Reasoning over Hierarchical Question Decomposition Tree (RoHT). First, we build the Hierarchical Question Decomposition Tree (HQDT) to understand the semantics of a complex question; then, we conduct probabilistic reasoning over HQDT from root to leaves recursively, to aggregate heterogeneous knowledge at different tree levels and search for a best solution considering the decomposing and answering probabilities. The experiments on complex QA datasets KQA Pro and Musique show that our framework outperforms SOTA methods significantly, demonstrating the effectiveness of leveraging question decomposing for knowledge integration and our RoHT framework.Comment: has been accepted by ACL202

LongAlign: A Recipe for Long Context Alignment of Large Language Models

Extending large language models to effectively handle long contexts requires instruction fine-tuning on input sequences of similar length. To address this, we present LongAlign -- a recipe of the instruction data, training, and evaluation for long context alignment. First, we construct a long instruction-following dataset using Self-Instruct. To ensure the data diversity, it covers a broad range of tasks from various long context sources. Second, we adopt the packing and sorted batching strategies to speed up supervised fine-tuning on data with varied length distributions. Additionally, we develop a loss weighting method to balance the contribution to the loss across different sequences during packing training. Third, we introduce the LongBench-Chat benchmark for evaluating instruction-following capabilities on queries of 10k-100k in length. Experiments show that LongAlign outperforms existing recipes for LLMs in long context tasks by up to 30\%, while also maintaining their proficiency in handling short, generic tasks. The code, data, and long-aligned models are open-sourced at https://github.com/THUDM/LongAlign

Nutrient content of 122 kinds of retail handcrafted milk tea products in Shanghai

BackgroundThe retail milk tea industry is in a period of rapid development, but there is little research on its nutrient content, which restricts the nutritional guidance of milk tea. ObjectiveTo determine the levels of nutrients in best-selling handcrafted milk tea in Shanghai and analyze the nutritional characteristics. MethodsIn 2018 and 2021, a total of 13 handcrafted milk tea brands with ≥3 branch stores in Shanghai were selected by searching for milk tea on Meituan and Ele.me food delivery platforms, and a total of 122 types of handcrafted milk tea products were collected from the top three sales [milk tea (including all sweetness levels available), milk cover tea, and fruit tea]. National standard methods were used to detect energy, protein, fat, carbohydrate, sugar, trans fatty acid, calcium, caffeine, and tea polyphenol. ResultsThe median energy of the milk tea samples was 310 kJ (per 100 g sample). The main sources of energy were carbohydrate and fat. The levels of energy, protein, and fat in milk cover tea and milk tea were significantly higher than those in fruit tea (P＜0.05), and there was no significant difference in carbohydrate among them. The total sugar, fructose, and glucose levels in milk tea were significantly lower than those in milk cover tea and fruit tea, and the lactose level in fruit tea was significantly lower than those in milk tea and milk cover tea (P＜0.05). Themedian trans fat acid level in milk cover tea was higher than that in milk tea (P＜0.05). The median levels of caffeine and tea polyphenol were higher in milk tea than in milk cover tea (P＜0.05). The levels of energy, carbohydrate, sucrose, total sugar, and calcium in milk tea were positively correlated with the number of ingredients added (0-3) (r=0.386, 0.371, 0.238, 0.698, 0.466, respectively, P < 0.05). The levels of energy, carbohydrate, and total sugar tended to increase with increasing sweetness (P<0.05), and total sugar was mainly sucrose, followed by fructose and glucose. The total sugar levels of the samples labeled sugar free, light sugar, half sugar, less sugar, and regular sugar were 3.40 (2.20, 4.9), 4.97 (4.25, 5.97), 5.80 (4.31, 6.88), 6.59 (5.17, 8.53), and 7.96 (6.82, 9.20) g, respectively; the proportions of the samples containing more than 0.5 g of total sugar were 93.3% for sugar free milk tea, 47.4% for light sugar milk tea, and 94.0% for regular sugar milk tea; the proportion of the regular sugar samples with sugar content greater than 10 g was 18.0% (all samples with nominal sugar content were measured per 100 g). ConclusionThe retail handcrafted milk tea in Shanghai is characterized by high energy, high added sugar, high fat, and low protein. It is necessary to standardize the added sugar content and sweetness labeling, strengthen the nutrition education of milk tea, and guide residents to limit its intake

Market Stakeholder Analysis of the Practical Implementation of Carbonation Curing on Steel Slag for Urban Sustainable Governance

Carbonation curing on steel slag is one of the most promising technologies for the iron and steel industry to manage its solid waste and carbon emissions. However, the technology is still in its demonstration stage. This paper investigates the market stakeholders of carbonation curing on steel slag for construction materials for its effective application by taking China as a case study. A holistic analysis of the competition, market size, and stakeholders of carbonation curing on steel slag was carried out through a literature review, a survey, a questionnaire, and interviews. The results showed that carbonation curing on steel slag had the advantages of high quality, high efficiency, low cost, and carbon reduction compared with other technologies. Shandong province was the most suitable province for the large-scale primary application of the technology. Stakeholder involvement to establish information platforms, enhance economic incentives, and promote adequate R&D activities would promote carbonation curing of steel slag into practice. This paper provides a reference for the commercialization of carbonation curing on similar calcium- and magnesium-based solid waste materials

Tunable Interband Transitions in Twisted h-BN/Graphene Heterostructures

In twisted h-BN/graphene heterostructures, the complex electronic properties of the fast-traveling electron gas in graphene are usually considered to be fully revealed. However, the randomly twisted heterostructures may also have unexpected transition behaviors, which may influence the device performance. Here, we study the twist angle-dependent coupling effects of h-BN/graphene heterostructures using monochromatic electron energy loss spectroscopy. We find that the moir\'e potentials alter the band structure of graphene, resulting in a redshift of the intralayer transition at the M-point, which becomes more pronounced up to 0.25 eV with increasing twist angle. Furthermore, the twisting of the Brillouin zone of h-BN relative to the graphene M-point leads to tunable vertical transition energies in the range of 5.1-5.6 eV. Our findings indicate that twist-coupling effects of van der Waals heterostructures should be carefully considered in device fabrications, and the continuously tunable interband transitions through the twist angle can serve as a new degree of freedom to design optoelectrical devices

Associations of sugar-sweetened beverages intake frequency with physical growth and glucolipid metabolism among children and adolescents

BackgroundChildren and adolescents drink sugar-sweetened beverages (SSBs) frequently. Research has confirmed that SSBs associate with weight gain and overweight or obesity. However, it is unclear whether high SSBs intake associates with abnormal changes in physical growth and glucolipid metabolism before causing adverse health outcomes such as overweight and obesity. Early identification of associated health risks of overconsumption of SSBs have important public health implications. ObjectiveTo investigate the differences in physical growth and glucolipid metabolism between different SSBs intake frequency groups in normal weight children and adolescents aged 6-17 years, and to evaluate the early effects of SSBs intake on physical growth and glycolipid metabolism before causing overweight and obesity, aiming to provide a scientific basis for the prevention and control of childhood overweight and obesity and related chronic diseases, and for the formulation of policies on the control of SSBs consumption. MethodsData were from the Shanghai Diet and Health Survey (SDHS) among primary and secondary school students. The participants were normal weight children and adolescents aged 6-17 years. Propensity scores were calculated according to energy intake and physical activity factors, after stratifying by age and gender. Participants were 1:1 matched with the closest propensity scores in the high-frequency (≥1 time·d−1) and the low-frequency (≤1 time·week−1) SSBs intake groups. The outcome indicators were physical measurements such as height, weight, percent of body fat, and waist circumference, and metabolic indicators such as fasting blood glucose, total triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Body mass index (BMI) was calculated. Food frequency questionnaire was used to collect SSBs consumption in the past three months through face-to-face interview. A paired t-test was used to compare the differences in physical and glycolipid metabolic indicators between the high-frequency intake group and the low-frequency intake group of SSBs. ResultsA total of 431 pairs were obtained. For children and adolescents in grades 6-9, overall height (difference=2.92 cm, P=0.002), weight (difference=2.53 kg, P=0.003), and waist circumference (difference=1.34 cm, P=0.035) were higher in those who consumed SSBs ≥1 time·d−1 than in those who consumed ≤1 time·week−1. For children and adolescents in grades 10-12, overall weight (difference=2.27 kg, P=0.041) was higher in those who consumed SSBs ≥1 time·d−1 than in those who consumed ≤1 time·week−1. Over 95% of the study subjects reported blood glucose and lipid test results within the normal range; but girls in grades 1-5 who consumed SSBs ≥1 time·d−1 had a higher total cholesterol (difference=0.20 mmol·L−1, P=0.027) and low-density lipoprotein cholesterol (difference=0.19 mmol·L−1, P=0.010) than those who consumed ≤1 time·week−1; boys in grades 6-9 who consumed SSBs ≥1 time·d−1 had a lower high-density lipoprotein cholesterol (difference=-0.10 mmol·L−1, P=0.039) than those who consumed ≤1 time·week−1. ConclusionHigh-frequency intake of SSBs may be associated with higher total cholesterol and low-density lipoprotein cholesterol in normal weight children and adolescents in grades 1-5, and higher weight in normal weight children and adolescents in grades 6-12. There is an urgent need to educate children and adolescents about nutritional health, enhance their ability to make healthy food and beverage choices, and take early interventions to control the intake of SSBs in children

An ancestral NB-LRR with duplicated 3'UTRs confers stripe rust resistance in wheat and barley.

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a global threat to wheat production. Aegilops tauschii, one of the wheat progenitors, carries the YrAS2388 locus for resistance to Pst on chromosome 4DS. We reveal that YrAS2388 encodes a typical nucleotide oligomerization domain-like receptor (NLR). The Pst-resistant allele YrAS2388R has duplicated 3' untranslated regions and is characterized by alternative splicing in the nucleotide-binding domain. Mutation of the YrAS2388R allele disrupts its resistance to Pst in synthetic hexaploid wheat; transgenic plants with YrAS2388R show resistance to eleven Pst races in common wheat and one race of P. striiformis f. sp. hordei in barley. The YrAS2388R allele occurs only in Ae. tauschii and the Ae. tauschii-derived synthetic wheat; it is absent in 100% (n = 461) of common wheat lines tested. The cloning of YrAS2388R will facilitate breeding for stripe rust resistance in wheat and other Triticeae species

Stem-cell-abundant proteins Nanog, Nucleostemin and Musashi1 are highly expressed in malignant cervical epithelial cells

<p>Abstract</p> <p>Background</p> <p>Nanog, nucleostemin (NS) and musashi1 (Msi1) are proteins that are highly expressed in undifferentiated embryonic stem (ES) cells and have been shown to be essential in maintaining the pluripotency and regulating the proliferation and asymmetric division of ES cells and several nervous system tumor cells. The roles of Nanog, NS and Msi1 in development and progression of cervical carcinoma have, until now, not been well documented.</p> <p>Methods</p> <p>In this study, expression of Nanog, NS and Msi1 was detected by immunohistochemistry analysis in 235 patients with various degrees of cervical epithelial lesions, including 49 with normal cervical epithelia, 31 with mild dysplasia (CIN I), 77 with moderate-severe dysplasia (CIN II-III) and 78 with squamous cervical carcinomas (SCCs). Associations with various clinical pathological prognostic variables were analyzed in 50 early-stage SCC patients.</p> <p>Results</p> <p>Nanog, NS and Msi1 expression levels were significantly higher in SCC patients compared with CIN patients, and were higher in CIN patients compared with those with normal cervical epithelia. Nanog expression levels showed significantly differences according to different tumor sizes (P < 0.05), whereas there were no differences in NS and Msi1 expression levels according to different clinical pathological parameters.</p> <p>Conclusion</p> <p>Our findings indicate that Nanog, NS and Msi1 may be involved in carcinogenesis of the cervix and progression of cervical carcinoma.</p