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Abstract Structure, stability, electronic structure, spectroscopy and chemical bonding properties of a fluorine atom doped gas-phase small to medium-sized magnesium clusters, FMgn (n = 2–20), systematically investigated by CALYPSO software together with density functional theory (DFT). Structural calculations showed that FMgn has a structural diversity which is rarely reported in other magnesium-based clusters before. F atoms were always located in the outer layer of the Mgn host clusters and only two or three Mg atoms surround it. FMg18 was revealed to be supposed to have robust relative stability. Charge transfer and density of states were calculated for analyzing the electronic structure characteristics. Theoretical calculations of IR, Raman and UV–Vis spectra were computed to provide data guidelines for future experimental observations. Finally, the F–Mg and Mg–Mg chemical bonds of the FMgn clusters were analyzed, including the critical bonding points (BCPs) of Laplacian of electron density (Δρ), electron localization function (ELF) and interaction region indicator (IRI). The kind and strength of chemical bonds reveal the mechanism by which the F atom was rapidly stabilized by Mgn (n = 2–20) host clusters.

Abstract The dynamics of proteins are crucial for understanding their mechanisms. However, computationally predicting protein dynamic information has proven challenging. Here, we propose a neural network model, RMSF-net, which outperforms previous methods and produces the best results in a large-scale protein dynamics dataset; this model can accurately infer the dynamic information of a protein in only a few seconds. By learning effectively from experimental protein structure data and cryo-electron microscopy (cryo-EM) data integration, our approach is able to accurately identify the interactive bidirectional constraints and supervision between cryo-EM maps and PDB models in maximizing the dynamic prediction efficacy. Rigorous 5-fold cross-validation on the dataset demonstrates that RMSF-net achieves test correlation coefficients of 0.746 ± 0.127 at the voxel level and 0.765 ± 0.109 at the residue level, showcasing its ability to deliver dynamic predictions closely approximating molecular dynamics simulations. Additionally, it offers real-time dynamic inference with minimal storage overhead on the order of megabytes. RMSF-net is a freely accessible tool and is anticipated to play an essential role in the study of protein dynamics.

Objective: This study aimed to explore the influencing factors of dynamic changes in traditional Chinese medicine (TCM) constitution based on general statistics, Apriori-DEMATEL algorithm, and DoWhy causal inference framework methods. Methods: Dynamic collection of TCM constitution identification data was conducted from the population aged 18 − 60, containing collection time and constitution type, and 11 constitution influencing factors including dietary habit, sleeping habit, sleeping duration, exercise habit, emotion state, stress level, living environment, work/life calamity, family atmosphere, business trip frequency, and overtime situation. General statistical analysis was used to analyze the relative percentage of corresponding influencing factors of different types of constitution changes, the Apriori-DEMATEL algorithm was used to analyze the correlation between 11 constitution influencing factors such as dietary habit and constitution changes, and the DoWhy causal inference framework was used to analyze the causality between dietary habit, sleeping habit, sleeping duration, exercise habit, emotion state, and stress level, explore the frequency of constitution type transformation-change factors, and determine the key influencing factors causing dynamic changes in constitution type. Results: After preprocessing, 13536 valid data points were obtained. Based on the Apriori-DEMATEL algorithm, the factors were divided into six original factors including dietary habit, sleeping habit, sleeping duration, exercise habit, emotion state, and stress level, and five result factors including living environment, work/life calamity, family atmosphere, business trip frequency, and overtime situation. Combining with general statistics, we found that among the original factors, changes in dietary habit, sleeping habit, sleeping duration, and stress level had a greater impact on other factors. In the process of constitution conditioning, attention should be paid to these four factors to maintain constitution balance. Among the five result factors, the absolute values of work/life calamity and family atmosphere were relatively large, indicating that these two factors were easily influenced by other factors. The dietary habit, sleeping habit, sleeping duration, exercise habit, emotion state, and stress level have higher centrality in changes, indicating that these six factors had important in constitution changes. According to the statistical frequency of constitution changes corresponding to each factor, we found that the changes of these six factors accounted for a large proportion of the constitution transformation frequency among Qi deficiency constitution, balanced constitution, and allergic constitution, indicating that the changes of these six factors played an important role in the changes of the three constitution types. Combined with the results of the Apriori-DEMATEL algorithm, and DoWhy causal inference framework analysis, it was inferred that dietary habit and sleeping duration indirectly lead to constitution changes by affecting the changes of other factors. Conclusion: This study explored the influencing factors of dynamic changes in TCM constitution from the perspective of dynamic data and multiple analysis methods, and the results showed that the changes of dietary habit, sleeping habit, sleeping duration, exercise habit, emotion state, and stress level had a great impact on the changes of Qi deficiency constitution, balanced constitution and allergic constitution. Attention should be paid to the changes of these six factors in daily life, and corresponding improvement plans should be formulated to reduce the probability of transforming into biased constitution. Our study also provided data support and objective analysis reference for the analysis of influencing factors of dynamic changes in TCM constitution types.

ABSTRACT: The aim of this study was to examine the effects of NH3 variations across different positions within a cage-reared duck house on the egg production performance and fecal microbiome in Muscovy ducks. Totals of 3,168 female Muscovy ducks (180 ± 2 d) were randomly assigned to 1,056 cages. From d 293 to 300, the egg production rate and levels of NH3, H2S, CO2, temperature, humidity, light intensity, and dust particles were recorded. Two spatial distribution-based experimental classification methods were applied, one grouping ducks into Front, Middle, and End categories, and the other into First, Second, and Third layers. On d 300, serum and feces samples were collected for further analysis. The result showed that both the egg production rate and serum PROG level in the Front were higher than End (P < 0.05). However, no significant differences were found among the First, Second, and Third groups. Among the environmental factors, ammonia (NH3) is a major harmful gas in cage-reared duck houses, with observed concentrations showing a gradient from lower levels in the Front group to higher levels in the Middle group (P < 0.05), and even higher levels in the End group (P < 0.05). Gene sequencing of the 16S rRNA gene revealed a higher relative abundance of Firmicutes in both the Front and Middle groups compared to the End group (P < 0.05). Specifically, within the Firmicutes phylum, the relative abundance of Lactobacillus and Romboutsia was notably higher in the Front group compared to both the Middle and End groups (P < 0.05). What's more, the abundance of Lactobacillus had a negative correlation with NH3 concentration and positive correlation with egg production rate. In conclusion, NH3 concentrations showed variations across different areas of the cage-reared duck house, with higher levels detected at the rear. The elevated NH3 level was identified as the main factor negatively impacting egg production in Muscovy ducks and contributing to a decline in the abundance of Firmicutes, specifically Lactobacillus.

Cancer is a major disease with ever-increasing morbidity and mortality. The metabolites derived from traditional Chinese medicine (TCM) have played a significant role in combating cancers with curative efficacy and unique advantages. Ferroptosis, an iron-dependent programmed death characterized by the accumulation of lipid peroxide, stands out from the conventional forms of cell death, such as apoptosis, pyroptosis, necrosis, and autophagy. Recent evidence has demonstrated the potential of TCM metabolites targeting ferroptosis for cancer therapy. We collected and screened related articles published in or before June 2023 using PubMed, Google Scholar, and Web of Science. The searched keywords in scientific databases were ferroptosis, cancer, tumor, traditional Chinese medicine, botanical drugs, and phytomedicine. Only research related to ferroptosis, the metabolites from TCM, and cancer was considered. In this review, we introduce an overview of the current knowledge regarding the ferroptosis mechanisms and review the research advances on the metabolites of TCM inhibiting cancer by targeting ferroptosis.

Abstract Gold(I)‐thiolate complexes have served as primary building blocks for diverse Au nanostructure synthesis strategies. A delicate approach to characterize and control Au(I)‐thiolate motif formation and assembly on the surface is needed as it can potentially solve challenges associated with utilizing gold nanomaterials in many applications. Here, the controllable generation of flower‐shaped surface gold nanostructures (FSGNs) is demonstrated by manipulating the formation‐assembly process of Au(I)‐dodecanethiolate motifs within nanoscale surface droplets. The morphology and structure of the resulting Au nanostructures are governed by internal convection flows and interfacial energy, modulated by the nanodroplet composition and substrate wettability. The obtained FSGNs are proven to act as versatile scaffolds for the selective generation of Au spiky nanostars. These FSGNs can also be utilized to functionalize nanodroplet‐based reactors, boosting the fluorescent intensity of Nile red (NR) fluorophores and decomposing NR via catalytic reaction. Remarkably, with FSGN functionalized droplets smaller than a radius of 500 nm, the decomposition rate of NR can reach ≈0.01 s−1. These results highlight a miniaturized, controllable, and automated method for the in situ production of 3D gold nanostructures on substrates, offering prospects for fast surface nanostructure fabrication and efficient environmental pollutant treatment.

Objective: In the RECO study, we investigated the impact of the operator's choice of stent retriever size on patients with internal carotid artery (ICA) occlusion. Methods: Data from the RECO Registry, a prospective multicentre study, were utilized. Patients who underwent mechanical thrombectomy (MT) were divided according to the size of the stent into the RECO 4 × 20 group, the RECO 5 × 30 group and the RECO 6 × 30 group. The outcome measures assessed in the study were the 3-month modified Rankin Scale (mRS) score, occurrence of any intracranial haemorrhage (aICH), workflow timing, recanalization success rate, number of attempts, and all-cause mortality within a 3-month period. Results: Analysis was conducted on a total of 89 patients with ICA occlusion. RECO 4 × 20, 5 × 30, and 6 × 30 stent retrievers were used in 19 (21.3%), 52 (58.4%), and 18 (20.2%) patients, respectively. The demographic and baseline characteristics showed considerable similarity across the three groups. The puncture-to-recanalization time of the RECO 6 × 30 group [56.5 min (IQR, 41.5–80.8)] was significantly shorter than that of the RECO 4 × 20 group [110 min (IQR, 47–135)]. In 10 out of 18 patients (55.6%), the RECO 6 × 30 stent retriever achieved reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score 2b-3) after the initial attempt, surpassing the rates of 31.6% in the RECO 4 × 20 group and 32.7% in the RECO 5 × 30 group. In the RECO 4 × 20 group, the median number of passes was 2 (IQR, 1–3); in the RECO 5 × 30 group, it was 2 (IQR, 1–3); and in the RECO 6 × 30 groups, it was 1 (IQR, 1–2.5). There were no statistically significant differences observed among the three groups concerning aICH or good outcomes (mRS score 0–2). Conclusion: Our study demonstrated the practical implications of stent-retriever size selection in the context of the MT for ICA occlusion. The routine use of a RECO 6 × 30 stent retriever holds the potential for early revascularization in clinical practice. The significant reduction in the puncture-to-reperfusion time and the greater first-pass effect associated with this stent size underscore its efficiency in treating ICA occlusion.

Background and objectives: The neutrophil-to-lymphocyte ratio (NLR) is a widely recognized marker of inflammation in peripheral blood. However, its specific role in neuronal intranuclear inclusion disease (NIID) has not been reported. This study aims to investigate the relationship between NIID and NLR. Methods: A multicenter database was collected, including 157 NIID patients from seven hospitals (The Affiliated Hospital of Xuzhou Medical University, Yantai Yuhuangding Hospital, Tengzhou Central People's Hospital,The Affiliated Brain Hospital of Nanjing Medical University, Liaocheng People's Hospital,The Second Hospital of Shandong University, Inner Mongolia People's Hospital, Xuanwu Hospital Capital Medical University,The First Affiliated Hospital of USTC), along with 157 age- and gender-matched healthy control subjects. White blood cell counts (including neutrophils, lymphocytes, monocytes, eosinophils, and basophils) were obtained, and the NLR was calculated. Additionally, cognitive impairment was assessed using clinical evaluation scores. Results: NIID patients exhibited significantly higher NLR values compared to the healthy control group (p 0.05). Conclusion: There is a significant association between NLR and NIID, suggesting a potential role of peripheral blood inflammation in the pathogenesis of NIID.

Abstract Background Woolly rhinoceros (Coelodonta antiquitatis) is a typical indicator of cold-stage climate that was widely distributed in Northern Hemisphere during the Middle-Late Pleistocene. Although a plethora of fossils have been excavated from Northern China, their phylogenetic status, intraspecific diversity and phylogeographical structure are still vague. Results In the present study, we generated four mitogenomes from Late Pleistocene woolly rhinoceros in Northern China and compared them with published data. Bayesian and network analyses indicate that the analyzed individuals contain at least four maternal haplogroups, and Chinese samples fall in three of them. One of our samples belongs to a previously unidentified early diverging clade (haplogroup D), which separated from other woolly rhinoceros around 0.57 Ma (95% CI: 0.76–0.41 Ma). The timing of this clade’s origin coincides with the first occurrence of woolly rhinoceros, which are thought to have evolved in Europe. Our other three samples cluster in haplogroup C, previously only identified from one specimen from Wrangel Island (ND030) and initially considered to be an isolated clade. Herein, our findings suggest that ND030 is likely descended from a northward dispersal of the individuals carrying haplogroup C from Northern China. Additionally, Chinese woolly rhinoceros specimens exhibit higher nucleotide diversity than those from Siberia. Conclusion Our findings highlight Northern China as a possible refugium and a key evolution center of the Pleistocene woolly rhinoceros.

This study addresses the issue of construction stagnation affecting the adhesion and tensile properties of hydraulic asphalt concrete with acid aggregate. It investigates the impact of rest periods on the tensile characteristics of such materials under standard construction conditions. The influence of varying rest durations and asphalt temperatures on the tensile behavior of the concrete is assessed through indoor experiments. The bonding between asphalt and aggregate is examined, along with the tensile property variations of the concrete. The study found that the standstill time significantly affects the adhesion of asphalt, with the adhesion decreasing progressively with increased temperature and rest time, irrespective of the addition of anti-stripping agents. However, the inclusion of these agents can mitigate the reduction in adhesion. Furthermore, the study identified that rest duration has a more substantial impact on adhesion than temperature. The splitting tests demonstrate that the tensile properties of asphalt concrete are considerably affected by the resting time. Over a period of 0, 10, 20, and 30 days of rest, an increase in splitting strength and a decrease in splitting displacement were observed. The findings offer valuable insights for predicting the tensile performance of asphalt concrete in practical engineering applications after a period of rest.

With the development of electronic warfare technology, the intelligent jammer dramatically reduces the performance of traditional radar anti-jamming methods. A key issue is how to actively adapt radar to complex electromagnetic environments and design anti-jamming strategies to deal with intelligent jammers. The space of the electromagnetic environment is dynamically changing, and the transmitting power of the jammer and frequency diversity array (FDA) radar in each frequency band is continuously adjustable. Both can learn the optimal strategy by interacting with the electromagnetic environment. Considering that the competition between the FDA radar and the jammer is a confrontation process of two agents, we find the optimal power allocation strategy for both sides by using the multi-agent deep deterministic policy gradient (MADDPG) algorithm based on multi-agent reinforcement learning (MARL). Finally, the simulation results show that the power allocation strategy of the FDA radar and the jammer can converge and effectively improve the performance of the FDA radar and the jammer in the intelligent countermeasure environment.

Abstract Mineral licks are indispensable habitats to the life history of large mammal herbivores (LMH). Geophagy at licks may provide the necessary minerals for LMH, while LMH may be ecosystem engineers of licks by altering vegetation cover and soil physicochemical properties (SPCP). However, the precise relationship between the LMH and licks remains unclear. To clarify the geophagy function of licks for LMH and their influence on soil at licks, we recorded visitation patterns of sika deer around licks and compared SPCP and microbial communities with the surrounding matrix in a firebreak adjacent to the Sino‐Russian border. Our study indirectly supports the “sodium supplementation” hypothesis. Proofs included (1) a significantly higher sodium, iron, and aluminum contents than the matrix, while lower carbon, nitrogen, and moisture contents; (2) significantly higher deer visitation during sodium‐demand season (growing season), along with an avoidance of licks with high iron contents, which is toxic when overdose. The microbes at the licks differed from those at the matrix, mainly driven by low soil carbon and nitrogen and altered biogeochemical cycles. The microbial communities of licks are vulnerable because of their unstable state and susceptibility to SPCP changes. Structural equation modeling (SEM) clearly showed a much stronger indirect effect of deer on microbes at licks than at the matrix, especially for bacteria. Multiple deer behaviors at licks, such as grazing, trampling, and excretion, can indirectly shape and stabilize microbes by altering carbon and nitrogen input. Our study is the first to characterize soil microbial communities at mineral licks and demonstrate the processes by which LMH shapes those communities. More studies are required to establish a general relationship between the LMH and licks to promote the conservation of natural licks for wildlife.

The gut microbiota of wild animals, influenced by various factors including diet, nutrition, gender, and age, plays a critical role in their health and disease status. This study focuses on raccoon dogs (Nyctereutes procyonoides), a commonly found wild animal, and its gut microbiota composition in response to dietary shifts. The study aimed to compare the fecal bacterial communities and diversity of rescued raccoon dogs fed three different diet types (fish and amphibians, mixed protein with maize, and solely maize) using high-throughput sequencing. Results indicated that the dietary composition significantly influenced the gut microbiota, with notable differences in the abundance of several key phyla and genera. The study identified Firmicutes as the dominant phylum in all diet groups, with notable variations in the relative abundances of Bacteroidota, Proteobacteria, and Verrucomicrobiota. Notably, the group solely fed maize exhibited a significant increase in Proteobacteria, potentially linked to dietary fiber and lignin degradation. The genus-level analysis highlighted significant differences, with Lactobacillus and Bifidobacterium responding to dietary shifts. The genus Akkermansia in Verrucomicrobiota can be identified as a marker for assessing the health of the gut and deserves further investigation. Gender-specific differences in the gut microbiota were observed, highlighting the influence of individual variation. Furthermore, the analysis of bacterial functions suggested a connection between diet and host metabolism, emphasizing the need for further research to understand the complex mechanisms underlying the relationship between dietary composition and gut microbiota in wild animals. These findings provide crucial insights into conservation and rescue efforts for wild animals.

Phascolosoma esculenta is an economically species inhabiting the intertidal zone and is farmed with high output. During artificial propagation, P. esculenta underwent mass death after torrential rain due to low salinity. In this paper, the effect of salinity on P. esculenta was studied for the first time. The results showed that P. esculenta died when exposed to water of 10‰ salinity, and their body lengths were about two times larger than when exposed to salinity of 25‰. The groups exposed to 10‰ salinity underwent severe necrosis. The activity of T-SOD and T-AOC in nephridial tissues increased between 3 and 12 h, but not at 9 h, T-SOD was highest in the control group and lowest in the death group, and T-AOC was highest in the death group and lowest in the survivor group. The concentration of MDA increased from 3 to 9 h and then decreased, and was highest in the death group and lowest in the control group. 35,053 unique genes, including 15,445 new genes, were acquired based on the 61.63 Gb Clean RNA-Seq Data. 27773 average alternative splicing (AS) events were found in the death group, which was 83.74% and 83.54% of that in the control and survivor group, respectively. Additionally, 1596 significantly differentially expressed genes (DEGs) were observed, which were classified into several functional categories, including genes involved in ion transporters, cation transport, RNA processing, immune response etc. The study had also found a significant number of genes involved in the pathways, including Mineral absorption, AMPK signaling pathway, Oxidative phosphorylation, and Phagosome pathways, such as Hsp70, Hsp20, Gst, solute carrier family genes, calcium channel regulatory activity genes, and pre-rRNA processing proteins. Overall, these results provide numerous candidate genes for future investigations and valuable insights into the mechanisms underlying the culture of P. esculenta in lower salinity.

Problem: Chest radiography is a crucial tool for diagnosing thoracic disorders, but interpretation errors and a lack of qualified practitioners can cause delays in treatment. Aim: This study aimed to develop a reliable multi-classification artificial intelligence (AI) tool to improve the accuracy and efficiency of chest radiograph diagnosis. Methods: We developed a convolutional neural network (CNN) capable of distinguishing among 26 thoracic diagnoses. The model was trained and externally validated using 795,055 chest radiographs from 13 datasets across 4 countries. Results: The CNN model achieved an average area under the curve (AUC) of 0.961 across all 26 diagnoses in the testing set. COVID-19 detection achieved perfect accuracy (AUC 1.000, [95% confidence interval {CI}, 1.000 to 1.000]), while effusion or pleural effusion detection showed the lowest accuracy (AUC 0.8453, [95% CI, 0.8417 to 0.8489]). In external validation, the model demonstrated strong reproducibility and generalizability within the local dataset, achieving an AUC of 0.9634 for lung opacity detection (95% CI, 0.9423 to 0.9702). The CNN outperformed both radiologists and nonradiological physicians, particularly in trans-device image recognition. Even for diseases not specifically trained on, such as aortic dissection, the AI model showed considerable scalability and enhanced diagnostic accuracy for physicians of varying experience levels (all P < 0.05). Additionally, our model exhibited no gender bias (P > 0.05). Conclusion: The developed AI algorithm, now available as professional web-based software, substantively improves chest radiograph interpretation. This research advances medical imaging and offers substantial diagnostic support in clinical settings.

Summary: The giant deer, widespread in northern Eurasia during the Late Pleistocene, have been classified as western Megaloceros and eastern Sinomegaceros through morphological studies. While Megaloceros’s evolutionary history has been unveiled through mitogenomes, Sinomegaceros remains molecularly unexplored. Herein, we generated mitogenomes of giant deer from East Asia. We find that, in contrast to the morphological differences between Megaloceros and Sinomegaceros, they are mixed in the mitochondrial phylogeny, and Siberian specimens suggest a range contact or overlap between these two groups. Meanwhile, one deep divergent clade and another surviving until 20.1 thousand years ago (ka) were detected in northeastern China, the latter implying this area as a potential refugium during the Last Glacial Maximum (LGM). Moreover, stable isotope analyses indicate correlations between climate-introduced vegetation changes and giant deer extinction. Our study demonstrates the genetic relationship between eastern and western giant deer and explores the promoters of their extirpation in northern East Asia.

Abstract Background The poor relationship between doctors and patients is a long-standing, global problem. However, current interventions tend to focus on the training of physicians, while patient-targeted interventions still need to be improved. Considering that patients play a significant role in outpatient consultations, we developed a protocol to assess the effectiveness of the Patient Oriented Four Habits Model (POFHM) in improving doctor-patient relationships. Methods A cross-sectional incomplete stepped-wedge cluster randomized trial design will be conducted in 8 primary healthcare institutions (PHCs). Following phase I of “usual care” as control measures for each PHC, either a patient- or doctor-only intervention will be implemented in phase II. In phase III, both patients and doctors will be involved in the intervention. This study will be conducted simultaneously in Nanling County and West Lake District. The primary outcomes will be evaluated after patients complete their visit: (1) patient literacy, (2) sense of control and (3) quality of doctor-patient communication. Finally, a mixed-effects model and subgroup analysis will be used to evaluate the effectiveness of the interventions. Discussion Fostering good consultation habits for the patient is a potentially effective strategy to improve the quality of doctor-patient communication. This study evaluates the implementation process and develops a rigorous quality control manual using a theoretical domain framework under the collective culture of China. The results of this trial will provide substantial evidence of the effectiveness of patient-oriented interventions. The POFHM can benefit the PHCs and provide a reference for countries and regions where medical resources are scarce and collectivist cultures dominate. Trial registration AsPredicted #107,282 on Sep 18, 2022; https://aspredicted.org/QST_MHW

Hydraulic asphalt concrete is known for its excellent seepage control performance and strong deformation resistance. This engineering material has widespread applications in the seepage control structures of hydraulic buildings. Recent projects have investigated the use of acidic aggregates to improve economic efficiency. However, they have also highlighted the weaker adhesion between acidic aggregates and asphalt, which necessitates stringent construction process control. This study investigates the impact of resting conditions on the tensile properties of acidic aggregate hydraulic asphalt concrete. The results of the tensile testing indicate that the storage time significantly affects the performance of asphalt concrete. The tensile strength of the specimens without anti-stripping agents decreased from 1.711 MPa to 0.914 MPa after resting periods of 0, 10, 20, and 30 days. The specimens treated with anti-stripping agents also showed a decrease in tensile strength over time, similar to the trend observed in the previous specimens. Digital specimen simulations indicated a decrease in cohesion between the asphalt and the aggregate from 5.375 MPa to 2.664 MPa after 30 days, representing a reduction of 50.44%. To counteract the effect of the storage time on the bonding between acidic aggregates and asphalt, this study recommends reducing the grading index and maximum size of aggregates, decreasing the coarse aggregate content, and selecting smooth aggregate shapes.

Severe bronchopulmonary dysplasia (BPD) is a chronic lung disorder that primarily affects premature babies with extremely low birth weight and involves in multiple organ system; no effective pharmacotherapy for this disease exists, and mortality remains high. Based on the evidence from previous preclinical studies and phase I clinical trials, this study aims to test the safety of intravenous application of a single dose of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in patients with severe BPD. The Mesenchymal Stem cells for Bronchopulmonary Dysplasia Treatment (MSBDT) trial is a single center, open-label, dose-escalation phase I clinical trial. Severe BPD patients were enrolled in Children Hospital of Chongqing Medical University, Chongqing, China. The first six patients were treated with low-dose hUC-MSCs (1 × 106 cells/kg) and the next seven patients were treated with high-dose hUC-MSCs (5 × 106 cells/kg). This study is registered with ClinicalTrials.gov, number NCT03558334. No prespecified infusion-associated adverse events, immediate complication, respiratory or cardiovascular compromise were observed during infusion and 24 h after infusion. No significant changes in safety laboratory values were observed. One death event occurred in the low-dose group on study day 10, and one death event occurred in the high-dose group on study day 24, while, after review in detail, the two cases are not believed to be infusion-associated events. In conclusion, intravenous application of a single dose of hUC-MSCs was tolerated in thirteen patients with severe BPD.

SAP30 is a core subunit of the transcriptional corepressor SIN3 complex, but little is known about its role in gene regulation and human cancer. Here, we show that SAP30 was a nonmutational oncoprotein upregulated in more than 50% of human breast tumors and correlated with unfavorable outcomes in patients with breast cancer. In various breast cancer mouse models, we found that SAP30 promoted tumor growth and metastasis through its interaction with SIN3A/3B. Surprisingly, the canonical gene silencing role was not essential for SAP30’s tumor-promoting actions. SAP30 enhanced chromatin accessibility and RNA polymerase II occupancy at promoters in breast cancer cells, acting as a coactivator for genes involved in cell motility, angiogenesis, and lymphangiogenesis, thereby driving tumor progression. Notably, SAP30 formed a homodimer with 1 subunit binding to SIN3A and another subunit recruiting MLL1 through specific Phe186/200 residues within its transactivation domain. MLL1 was required for SAP30-mediated transcriptional coactivation and breast tumor progression. Collectively, our findings reveal that SAP30 represents a transcriptional dependency in breast cancer.

Objectives Workplace violence (WPV) against healthcare workers (HCWs) is a global issue. Our research aimed to elucidate the status and associated factors of WPV among front-line/non-front-line HCWs during the COVID-19 pandemic.Design This cross-sectional study was conducted among HCWs in Hangzhou City through multistage sampling from December 2020 to January 2021.Participants This study included 14 909 valid samples (N=3748 front-line HCWs and N=11 161 non-front-line HCWs).Primary and secondary outcome measures We assessed the WPV status by Chinese version of WPV questionnaire. Binary logistic regression model was established to examine the associated factors of front-line/non-front-line HCWs experiencing WPV.Results The total WPV prevalence equalled 37.25% for front-line HCWs and 27.73% for non-front-line HCWs. Among front-line HCWs, females were less likely to experience WPV (OR 0.837, 95% CI 0.710 to 0.988), while individuals who were undergraduate (OR 1.251, 95% CI 1.061 to 1.541) and had higher professional title (intermediate: OR 1.475, 95% CI 1.227 to 1.772; advanced: OR 1.693, 95% CI 1.294 to 2.216) were more likely to suffer from WPV; for non-front-line HCWs, individuals who aged over 50 years old (OR 0.721, 95% CI 0.563 to 0.969), had worked between 10 and 19 years (OR 0.847, 95% CI 0.749 to 0.958) and worked in the non-graded hospital (OR 0.714, 95% CI 0.614 to 0.832) had less chance to experience WPV, while individuals who had higher educational level (undergraduate: OR 1.323, 95% CI 1.179 to 1.484; ≥graduate: OR 1.519, 95% CI 1.217 to 1.895), were nurse (OR 1.142, 95% CI 1.031 to 1.265), and had higher professional title (intermediate: OR 1.458, 95% CI 1.297 to 638; advanced: OR 1.928, 95% CI 1.607 to 2.313) were more inclined to suffer from WPV (p all

IntroductionInflammatory epidermolysis bullosa acquisita (EBA) is characterized by a neutrophilic response to anti-type VII collagen (COL7) antibodies resulting in the development of skin inflammation and blistering. The antibody transfer model of EBA closely mirrors this EBA phenotype.MethodsTo better understand the changes induced in neutrophils upon recruitment from peripheral blood into lesional skin in EBA, we performed single-cell RNA-sequencing of whole blood and skin dissociate to capture minimally perturbed neutrophils and characterize their transcriptome.ResultsThrough this approach, we identified clear distinctions between circulating activated neutrophils and intradermal neutrophils. Most strikingly, the gene expression of multiple C-type lectin receptors, which have previously been reported to orchestrate host defense against fungi and select bacteria, were markedly dysregulated. After confirming the upregulation of Clec4n, Clec4d, and Clec4e in experimental EBA as well as in lesional skin from patients with inflammatory EBA, we performed functional studies in globally deficient Clec4e−/− and Clec4d−/− mice as well as in neutrophil-specific Clec4n−/− mice. Deficiency in these genes did not reduce disease in the EBA model.DiscussionCollectively, our results suggest that while the upregulation of Clec4n, Clec4d, and Clec4e is a hallmark of activated dermal neutrophil populations, their individual contribution to the pathogenesis of EBA is dispensable.

The gas-phase Cn (n = 6–31) carbocyclic clusters were systematically investigated based on DFT using ABCluster software. In this work, two geometrical parameters, degree of circularity and the ratio of carbon atoms occupying the fitted circle, were defined for the geometrical circle formed by Cn (n = 6–31) carbocyclic by curve-fitting the coordinates of the carbon atoms, and it is found that even-numbered carbon rings are always more rounded than odd-numbered ones. The study of relative stability of Cn ring clusters, on the one hand, revealed that even carbon rings are always more stable than odd ones. On the other hand, it proved that cyclic shape carbon clusters are always more stable than cage-like structure ones. In addition, the density of states, simulated electron absorption spectra, polarization response to electrostatic field, π-electron population, and topological properties of bond critical points were compressively studied. This work effectively filled the lack of research on odd-numbered carbocycles, a member of the carbocyclic family, and showed readers the physical and chemical reasons for the relative deformation of odd-numbered carbocycles.

Abstract Frequency diversity array (FDA) radar provides more degrees of freedom and can generate range‐angle‐time‐dependent beampattern. Furthermore, based on the receiver's multi‐input multi‐output (MIMO) scheme, the frequency diversity array‐multi‐input multi‐output (FDA‐MIMO) radar can develop a range‐dependent but time‐independent beampattern. Taking advantage of this feature, this article improves the signal‐to‐interference‐plus‐noise ratio and the effective suppression of interference by jointly optimising the transmit beamspace and the receive filter. Since the optimisation problem is a non‐convex problem with constant energy constraints, we transform it into two convex subproblems with restrictions. The whole algorithm follows the alternate optimisation over receive filter and transmit beamspace. By simulating challenging scenarios, we confirmed the effectiveness and superiority of the method.

The gut microbiota is a complex ecosystem that interacts with many other factors to affect the health and disease states of the host. The common kestrel (Falco tinnunculus) is protected at the national level in China. However, the available sequencing data of the gut microbiota from the feces of wild common kestrels, especially for being rescued individuals by professional organization, remains limited. In the present study, we characterized the fecal bacterial communities of healthy and injured common kestrels, and compared the structure of their fecal microbiota by analyzing the V3–V4 region of the 16S rRNA gene using high-throughput sequencing technology with the Illumina MiSeq platform. We found that Firmicutes, Proteobacteria and Actinobacteria were the most predominant phyla in common kestrels. Further, the beta diversity analysis showed that changes in gut microbes were associated with injuries to the common kestrel. The Bacteroides/Firmicutes ratio was significantly lower in the injured group. At the genus level, Glutamicibacter showed significant difference in the two groups. The aim of our current study was to characterize the basic bacterial composition and community structure in the feces of healthy common kestrels, and then compare the differences in the fecal microbiota between healthy and injured individuals. Patescibacteria, Spirochaetes, and Glutamicibacter may be studied as potential biomarkers for certain diseases in raptors. The results could provide the basic data for additional research on the fecal microbiota of common kestrels and contribute to the rescue of wild raptors in the future.

Lysine-specific demethylase 1 (LSD1) is an enzyme that removes lysine methylation marks from nucleosome histone tails and plays an important role in cancer initiation, progression, metastasis, and recurrence. Recent research shows that LSD1 regulates tumor cells and immune cells through multiple upstream and downstream pathways, enabling tumor cells to adapt to the tumor microenvironment (TME). As a potential anti-tumor treatment strategy, immunotherapy has developed rapidly in the past few years. However, most patients have a low response rate to available immune checkpoint inhibitors (ICIs), including anti-PD-(L)1 therapy and CAR-T cell therapy, due to a broad array of immunosuppressive mechanisms. Notably, inhibition of LSD1 turns “cold tumors” into “hot tumors” and subsequently enhances tumor cell sensitivity to ICIs. This review focuses on recent advances in LSD1 and tumor immunity and discusses a potential therapeutic strategy for combining LSD1 inhibition with immunotherapy.

Context: Kaihoujian Throat Spray children's type (KHJSC) is a Chinese medicine prescription for treating pediatric acute pharyngitis and tonsillitis (APT). However, its relevant mechanisms remain unclear. Objective: To investigate the pharmacological effects of KHJSC on APT in vitro and in vivo, and explore the possible mechanism and target proteins. Materials and methods: The antiviral and antibacterial effects in vitro were evaluated by IC50 and MICs. Thirty-six Japanese white rabbits were averagely divided into control group, model group, amoxicillin group and 3 dose groups of KHJSC (720, 540 and 360 μL/kg/d). The model rabbits were injected with β-hemolytic Streptococcus solution into the tonsils for 2 consecutive days. KHJSC treatment started on the third day. The whole blood, serum, tonsil tissues and pharyngeal mucosa tissues were collected for routine blood tests, proteomic, ELISA and other tests on the sixth day. Results: The IC50 of KHJSC on HCoV-229E, influenza PR8 and Ad3 were 1.99, 1.99 and 4.49 mg/mL, respectively; MICs of MDR-PA, MRSA and β-hemolytic Streptococcus were 350, 350, and 175 mg/mL. KHJSC markedly decreased the number of white blood cells, lymphocytes, neutrophils, and the level of IL-1β, IL-5, IL-6, IL-18, TNF-α and MCP-1; increased the content of IL-2 and IFN-γ. Proteomic analysis and ELISA revealed that PI3K-Akt signaling pathway, NF-κB signaling pathway and Toll-like receptor signaling pathway were the potential mechanisms of KHJSC against APT. Discussion and conclusion: These results provided the reference and scientific basis for the application of KHJSC in clinic and further mechanisms study.

Abstract Transient receptor potential channel TRPM2 is highly expressed in many cancers and involved in regulation of key physiological processes including mitochondrial function, bioenergetics, and oxidative stress. In Stage 4 non-MYCN amplified neuroblastoma patients, high TRPM2 expression is associated with worse outcome. Here, neuroblastoma cells with high TRPM2 expression demonstrated increased migration and invasion capability. RNA sequencing, RT-qPCR, and Western blotting demonstrated that the mechanism involved significantly greater expression of integrins α1, αv, β1, and β5 in cells with high TRPM2 expression. Transcription factors HIF-1α, E2F1, and FOXM1, which bind promoter/enhancer regions of these integrins, were increased in cells with high TRPM2 expression. Subcellular fractionation confirmed high levels of α1, αv, and β1 membrane localization and co-immunoprecipitation confirmed the presence of α1β1, αvβ1, and αvβ5 complexes. Inhibitors of α1β1, αvβ1, and αvβ5 complexes significantly reduced migration and invasion in cells highly expressing TRPM2, confirming their functional role. Increased pAktSer473 and pERKThr202/Tyr204, which promote migration through mechanisms including integrin activation, were found in cells highly expressing TRPM2. TRPM2 promotes migration and invasion in neuroblastoma cells with high TRPM2 expression through modulation of integrins together with enhancing cell survival, negatively affecting patient outcome and providing rationale for TRPM2 inhibition in anti-neoplastic therapy.

Molecular dynamic simulations are employed to assess the influence of metal ions on riboswitch structure and dynamics, suggesting a conformational control of riboswitch aptamers by metal ions before ligand binding.

Abstract Background Uterine somatic choriocarcinoma is a rare, clinically aggressive malignant tumor. They frequently concur with other cancer. However, the molecular pathogenesis between somatic choriocarcinoma and the concurrent carcinoma has rarely been addressed to date. Case presentation We report a 68-years old Chinese woman with a uterine choriocarcinoma arising from serous carcinoma. The patient underwent radical surgery including total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy and pelvic lymph node resection. She received 10 courses of post-operative chemotherapy. She died of disease 13 months after her surgery. Microscopically, the tumor showed a biphasic pattern of choriocarcinoma and serous carcinoma. The choriocarcinomatous component showed a combination of cytotrophoblast, intermediate trophoblast and syncytiotrophoblast with hemorrhage and necrosis. The component of serous carcinoma was characterized by solid sheets of small cells with marked nuclear atypia and occasional glandular and papillary formation. PD-L1 was exclusively expressed in the choriocarcinomatous component. Next-generation sequencing revealed that the genetic abnormalities were overlapping between the two components.

Abstract Tertiary relict flora in East Asia can be divided into northern and southern regions. North China is a diversity hotspot because it can be the secondary contact zone of ancient lineages from the two regions. To test the extent of ancient lineages hybridization and distinguish between the putative species pair Acer pictum subsp. mono and Acer truncatum, we conducted genetic and ecological studies within a maple hybrid zone in North China. Our results suggest that the two lineages of Acer coexist in the hybrid zone and that adult and offspring populations show typical bimodal genetic patterns. Hybrid individuals are established at intermediate altitudes between the two parental lineages. Flowering phenology is divergent between lineages, whereas the complex sexual system of Acer may ensure pollination among lineages. Leaf and fruit morphologies are different between the northern and southern origin lineages, corresponding to A. pictum subsp. mono and A. truncatum, respectively. Reduced gene flow between lineages suggests that they should be considered as two species. However, large morphological variations within each species and the existence of hybrids offer low reliability of species identification based solely on morphological traits. Our study underscores North China as an overlooked diversity hotspot that requires further study in the future.

Abstract Background Fentanyl is an opioid analgesic and is widely used in ovarian cancer patients for pain management. Although increasing evidence has suggested the direct role of fentanyl on cancer, little is known on the effect of fentanyl on ovarian cancer cells. Methods Proliferation, migration and apoptosis assays were performed in ovarian cancer cells after fentanyl treatment. Xenograft mouse model was generated to investigate the in vivo efficacy of fentanyl. Combination index was analyzed for the combination of fentanyl and chemotherapeutic drugs. Immunoblotting approach was used to analyze signaling involved in fentanyl’s action focusing on EGFR. Results Fentanyl at nanomolar concentration does-dependently increased migration and proliferation of a panel of ovarian cancer cell lines. Fentanyl at the same concentrations either did not or stimulated proliferation to a less extent in normal cells than in ovarian cancer cells. Consistently, fentanyl significantly promoted ovarian cancer growth in vivo. The combination of fentanyl with cisplatin or paclitaxel was antagonist in inhibiting cell proliferation. Although fentanyl did not affect cell apoptosis, it significantly alleviated ovarian cancer cell death induced by chemotherapeutic drugs. Mechanistically, fentanyl specifically activated EGFR and its-mediated downstream pathways. Knockdown of EGFR abolished the stimulatory effects of fentanyl on ovarian cancer cells. We finally demonstrated that the activation of EGFR by fentanyl is associated with opioid µ receptor system. Conclusions Fentanyl activates ovarian cancer via simulating EGFR signaling pathways in an opioid µ receptor-dependent manner. The activation of EGFR signaling by fentanyl may provide a new guide in clinical use of fentanyl in ovarian cancer patients.

Background The role of thyroid hormones is crucial in the response to stress and critical illness, which has been reported to be closely associated with a poor prognosis in patients admitted to the intensive care unit (ICU). This study aimed to explore the relationship between thyroid hormone and prognosis in septic shock patients. Methods A total of 186 patients with septic shock were enrolled in the analytical study between December 2014 and September 2022. The baseline variables and thyroid hormone were collected. The patients were divided into survivor group and non-survivor group according to whether they died during the ICU hospitalization. Among 186 patients with septic shock, 123 (66.13%) were in the survivor group and 63 (33.87%) were in the non-survivor group. Results There were significant differences in the indictors of free triiodothyronine (FT3) (p = 0.000), triiodothyronine (T3) (p = 0.000), T3/FT3 (p = 0.000), acute physiology and chronic health evaluation II score (APACHE II) (p = 0.000), sequential organ failure assessment score (SOFA) (p = 0.000), pulse rate (p = 0.020), creatinine (p = 0.008), PaO2/FiO2 (p = 0.000), length of stay (p = 0.000) and hospitalization expenses (p = 0.000) in ICU between the two groups. FT3 [odds ratio (OR): 1.062, 95% confidence interval(CI): (0.021, 0.447), p = 0.003], T3 (OR: 0.291, 95% CI: 0.172-0.975, p = 0.037) and T3/FT3 (OR: 0.985, 95% CI:0.974-0.996, p = 0.006) were independent risk factors of the short-term prognosis of septic shock patients after adjustment. The areas under the receiver operating characteristic curves for T3 was associated with ICU mortality (AUC = 0.796, p

Abstract Thin film transistors (TFTs) are key components for the fabrication of electronic and optoelectronic devices, resulting in a push for the wider exploration of semiconducting materials and cost‐effective synthesis processes. In this report, a simple approach is proposed to achieve 2‐nm‐thick indium oxide nanosheets from liquid metal surfaces by employing a squeeze printing technique and thermal annealing at 250 °C in air. The resulting materials exhibit a high degree of transparency (>99 %) and an excellent electron mobility of ≈96 cm2 V−1 s−1, surpassing that of pristine printed 2D In2O3 and many other reported 2D semiconductors. UV‐detectors based on annealed 2D In2O3 also benefit from this process step, with the photoresponsivity reaching 5.2 × 104 and 9.4 × 103 A W−1 at the wavelengths of 285 and 365 nm, respectively. These values are an order of magnitude higher than for as‐synthesized 2D In2O3. Utilizing transmission electron microscopy with in situ annealing, it is demonstrated that the improvement in device performances is due to nanostructural changes within the oxide layers during annealing process. This work highlights a facile and ambient air compatible method for fabricating high‐quality semiconducting oxides, which will find application in emerging transparent electronics and optoelectronics.

ObjectiveThis study was designed to assess ferroptosis regulator gene (FRG) expression patterns in patients with TNBC based on data derived from The Cancer Genome Atlas (TCGA). Further, it was utilized to establish a TNBC FRG signature, after which the association between this signature and the tumor immune microenvironment (TIME) composition was assessed, and relevant prognostic factors were explored.MethodsThe TCGA database was used to obtain RNA expression datasets and clinical information about 190 TNBC patients, after which a prognostic TNBC-related FRG signature was established using a least absolute shrinkage and selection operator (LASSO) Cox regression approach. These results were validated with separate data from the Gene Expression Omnibus (GEO). The TNBC-specific prognostic gene was identified via this method. The STEAP3 was then validated through Western immunoblotting, immunohistochemical staining, and quantitative real‐time polymerase chain reaction (RT-qPCR) analyses of clinical tissue samples and TNBC cell lines. Chemotherapy interactions and predicted drug sensitivity studies were investigated to learn more about the potential clinical relevance of these observations.ResultsThese data revealed that 87 FRGs were differentially expressed when comparing TNBC tumors and healthy tissue samples (87/259, 33.59%). Seven of these genes (CA9, CISD1, STEAP3, HMOX1, DUSP1, TAZ, HBA1) are significantly related to the overall survival of TNBC patients. Kaplan-Meier analyses and established FRG signatures and nomograms identified CISD1 and STEAP3 genes of prognostic relevance. Prognostic Risk Score values were positively correlated with the infiltration of CD4+ T cells (p = 0.001) and myeloid dendritic cells (p =0.004). Further evidence showed that STEAP3 was strongly and specifically associated with TNBC patient OS (P

BackgroundMesenchymal stem cells (MSCs) are multipotent stromal cells that have been reported to possess great potential for the treatment of bronchopulmonary dysplasia (BPD).ObjectiveOur study aims to assess the effects of three different doses of intraperitoneal administration of human umbilical cord-derived MSCs (hUC-MSCs) on a hyperoxia-induced BPD model of newborn rat.MethodsNeonatal Sprague Dawley (SD) rats were reared in either hyperoxia (75% O2) or room air (RA) from postnatal days (PN) 1-14. At PN5, hUC-MSCs (1 × 106, 5× 106,or 1× 107 cells per pup) were given intraperitoneally to newborn rats exposed to 75% O2 from birth; the controls received an equal volume of normal saline (NS). At PN14, the lung tissues, serum, and bronchoalveolar fluid (BALF) were collected for histologic examination, wet/dry (W/D) weight ratio analysis, engraftment, myeoloperoxidase (MPO) activity analysis, cytokine analysis, and western blot analysis of protein expression.ResultsCompared to rat pups reared in RA, rat pups reared in hyperoxia had a significant lower survival rate (53.3%) (P < 0.01). Hyperoxia-exposed rats exhibited pulmonary inflammation accompanied by alveolar-capillary leakage, neutrophile infiltration, augmented myeloperoxidase (MPO) activity, prominent alveolar simplification, and increased mean linear intercept (MLI), which was ameliorated by hUC-MSCs treatment. Increased oxidative stress and inflammatory cytokine production were also reduced. Importantly, the expression of Fas, an apoptosis-associated protein that was increasingly expressed in hyperoxia-exposed rats (P < 0.05), was downregulated after administration of hUC-MSCs (P < 0.05).ConclusionsOur results suggest that intraperitoneal administration of high number hUC-MSCs (1 × 107 cells) may represent an effective modality for the treatment of hyperoxia-induced BPD in neonatal rats.

In this study, the double screw lifting device of a rubber factory is taken as the case study object, and a scale model experiment was designed to determine the temperature field, velocity field and concentration field of pollutant escape of double spiral lifting transportation device are compared, and the capture efficiency is compared under the conditions of different dimensionless installation height and local exhaust hood air flow velocity Vexh. Reduced-scale experiments were conducted with a geometric scale of 1:4. Compared with no local exhaust hood, the concentration at the same measuring point decreases significantly under the action of local exhaust hood (dimensionless distances z/d = 3/4 and z/d = 2/4). Under the condition of maintaining the same local exhaust hood air flow velocity Vexh, the capture efficiency of local exhaust hood increased by 4% and 1% respectively on the dimensionless installation distance Z/D was 3/4 and 2/4 respectively. The experimental method of this case study and the air flow field experimental data obtained can provide a reference for the subsequent design and installation of exhaust hood.

The transmitted beam of frequency diversity array (FDA) has the range–angle–time coupling property, which has essential applicative potential in angle deception and active anti-jamming. In this paper, the concept of time index within pulse is introduced. Firstly, the phase characteristics of FDA-transmitted signals based on the time index within pulse concept are studied. Then, the deceptive angle performance of FDA-transmitted signals is discussed. The theoretical analysis and simulation results show that the phase characteristics of the FDA signal are not related to the range, but to the time index within pulse. With the phase center as the reference point, the phase is equal as long as the time index within the pulse is the same. Angle deception and active anti-jamming can be achieved using the optimized frequency increment of each FDA.

The study of the reservoir architecture in braided river systems has significant implications for the exploitation of remaining oil and gas reserves. However, due to the complexity of the braided river deposition process, the architecture patterns are diverse and intricate. Limited by the quality of seismic data and well network density, the characterization of underground reservoir architecture often entails considerable uncertainty. This paper investigates the architecture elements, stacking patterns, and significance of oil and gas development in the braided river deposition of the Jin 58 well area in the northern part of the Ordos Basin through typical field outcrop and core observations, and by making full use of horizontal well data. The study reveals that the Jin 58 well area is mainly characterized by four types of architecture units: braided channel, channel bar, overbank, and flood plain. Based on the data from horizontal and vertical wells, four identification criteria for single sand bodies are determined, and the vertical stacking and lateral juxtaposition styles of the architecture units, as well as the architecture patterns and internal features of the channel bar, are summarized. It is confirmed that composite sand bodies have better productivity. A three-dimensional architecture model of the braided river is established based on the results of architecture analysis. The accuracy of the architecture analysis is validated through numerical simulation, providing a basis for subsequent well deployment and other related activities.

In this study, a conceptual framework of measurement uncertainty was developed and used to guide the development of a multiple-choice concept test for the assessment of students’ knowledge integration in learning measurement uncertainty. Based on assessment data and interview results, students were identified into three levels of knowledge integration including novice, intermediate, and expertlike. The reasoning pathways of students at different levels revealed a progression of reasoning from a rudimentary surface level to a deep understanding that can be mapped in the conceptual framework. This work demonstrates the possibility of identifying a quantitative categorization scheme to model knowledge integration as well as its utility in teaching and learning. Overall, the assessments and interviews revealed common and persistent difficulties in students’ understanding of measurement uncertainty. In addition, students at different levels of knowledge integration demonstrate unique types of knowledge states that can be represented in the conceptual framework, making it a useful tool for analyzing different reasoning pathways and knowledge structures.

Achieving knowledge integration for deep learning requires students to develop well-connected knowledge structures through the central idea of a concept. However, a number of studies on student learning in momentum have revealed persistent difficulties in understanding its fundamental concept, particularly in relating net force, time, and change in momentum with each other. This study evaluates the effectiveness of a teaching intervention based on the conceptual framework of momentum that targets knowledge integration. The evaluation outcomes of the intervention provide encouraging evidence suggesting that the conceptual framework model can be a valuable guide to the development of instruction for promoting knowledge integration and deep learning.

Abstract Transient receptor potential channel melastatin 2 (TRPM2) is highly expressed in cancer and has an essential function in preserving viability through maintenance of mitochondrial function and antioxidant response. Here, the role of TRPM2 in cell survival was examined in neuroblastoma cells with TRPM2 deletion with CRISPR technology. Viability was significantly decreased in TRPM2 knockout after doxorubicin treatment. RNA sequence analysis and RT-qPCR revealed reduced RNAs encoding master transcription regulators FOXM1 and E2F1/2 and downstream cell cycle targets including Cyclin B1, CDK1, PLK1, and CKS1. CHIP analysis demonstrated decreased FOXM1 binding to their promoters. Western blotting confirmed decreased expression, and increased expression of CDK inhibitor p21, a CKS1 target. In cells with TRPM2 deletion, cell cycle progression to S and G2/M phases was reduced after treatment with doxorubicin. RNA sequencing also identified decreased DNA repair proteins in cells with TRPM2 deletion after doxorubicin treatment, and DNA damage was increased. Wild type TRPM2, but not Ca2+-impermeable mutant E960D, restored live cell number and reconstituted expression of E2F1, FOXM1, and cell cycle/DNA repair proteins. FOXM1 expression alone restored viability. TRPM2 is a potential therapeutic target to reduce tumor proliferation and increase doxorubicin sensitivity through modulation of FOXM1, E2F1, and cell cycle/DNA repair proteins.

BackgroundThe number of people suffering from overweight or obesity has been steadily increasing in recent years. As a new form of diet, the efficacy of time-restricted eating (TRE) remains debatable.ObjectiveThis meta-analysis quantified the effect of TRE on weight change and other physical parameters in obese and overweight adults.MethodsWe did a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the TRE interventions on weight loss and other metabolic parameters by searching PubMed, Embase, and Cochrane Central Register of Controlled Trials to identify eligible trials published from database inception up until 23 August 2022. The risk of bias was assessed using the Revised Cochrane risk-of-bias tool (ROB-2.0). Meta-analysis was performed using Review Manager 5.4.1 software.ResultsNine RCTs with 665 individuals (345 in the TRE group while 320 in the control group) were included. Results indicated that TRE had a greater decrease in body weight (−1.28 kg; 95% CI [−2.05, −0.52], p = 0.001), fat mass (−0.72 kg; 95% CI [−1.40, −0.03], p = 0.04), body mass index (−0.34 kg/m2; 95% CI [−0.64, −0.04], p = 0.03) and diastolic blood pressure (−2.26 mmHg 95% CI [−4.02, −0.50], p = 0.01). However, the meta-analysis demonstrated that there was no significant difference between TRE and the control group in lean mass, systolic blood pressure, waist circumference, fasting glucose, fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR), total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. Besides, the duration of the study and daily eating window also had an impact on weight change.ConclusionTRE was associated with reductions in weight and fat mass and can be a dietary intervention option for adults with obesity. But high-quality trials and longer follow-ups are needed to draw definitive conclusions.

By employing a tiny frequency offset across the array elements, a frequency diverse array (FDA) produces a beampattern with the property of being range-angle-dependent. However, the beampattern of a traditional FDA has many maxima at undesired range-angle couples, which is unfavorable for target localization and jamming suppression. In this paper, a novel FDA scheme with Hamming interelement spacing, namely, the HIS-FDA, is proposed. By adopting Hamming window weighted interelement spacing and frequency offsets optimized by the genetic algorithm, the HIS-FDA produces a dot-shaped well-performed beampattern, which has superior performance over the existing FDA systems, especially in the angle dimension. The multiple input multiple output technique and multiple matched filters are employed at the receiver to solve the time-varying problem. A new multicarrier (MC) technique termed the sinusoidal MC approach is also presented to improve the beampattern performance, especially in the range dimension. Our proposed scheme outperforms the existing FDA systems in terms of the mainlobe width in the range and angle profiles, the sidelobe level, and the range-angle spatial region of the mainlobe. Comparison results are provided to validate the superiority of the proposed scheme.

Background Over the past few decades, more studies have suggested that the age at menarche (AAM) has continued to decline. However, the AAM for women in resource-constrained areas is not clear. Moreover, the association between the Chinese famine and AAM is still unclear in rural regions. Aim The study aimed to investigate the secular trends of AAM for women born between 1935 and 2000 and to further explore the effect of famine on AAM in rural China. Subjects and methods The study included 23,444 women participants from the baseline study of the Henan Rural Cohort study. Changing AAM over time was analysed using linear regressions. Multinomial logistic regression was conducted to analyse the association between famine exposure and AAM subgroups. Results The age-standardised mean AAM was 14.74 years. The average AAM declined from 16.98 years for those born in 1935 to 13.87 years for those born in 2000, a decline of 0.077 years per 1 year and 0.729 years per decade. Compared to the reference group, women exposed to famine during foetal, early childhood, middle childhood, and late childhood were 1.376 (95% CI = 1.071–1.769), 1.848 (95% CI = 1.512–2.259), 2.084 (95% CI = 1.725–2.518), and 2.146 (95% CI = 1.788–2.576) times more likely to be ≥18 years AAM than women unexposed to famine, respectively. Conclusion AAM showed a decreasing trend in rural China. Furthermore, both foetal and childhood famine exposure, especially in late childhood, were positively associated with increased AAM compared to unexposed famine.

This paper deals with the problem of robust beamforming and target power estimation in the presence of main-lobe interference with frequency division array multiple-input multiple-output (FDA-MIMO) radar by adopting a weighting matrix at the receiving end. Based on the semi-definite programming (SDP) to solve the covariance matrix of the weighting matrix, we propose two beamforming methods and two methods for estimating the target power when the interference has a position error. Then, we propose obtaining the weighting matrix by performing singular value decomposition on the covariance matrix. We confirm the effectiveness of the developed method by comparing beam pattern and target signal estimation performance.

Plastics in the environment can break down into nanoplastics (NPs), which pose a potential threat to public health. Studies have shown that the nervous system constitutes a significant target for nanoplastics. However, the potential mechanism behind nanoplastics’ neurotoxicity remains unknown. This study aimed to investigate the role of lncRNA in the depressive-like responses induced by exposure to 25 nm polystyrene nanoplastics (PS NPs). Forty mice were divided into four groups administered doses of 0, 10, 25, and 50 mg/kg via gavage for 6 months. After conducting behavioral tests, RNA sequencing was used to detect changes in mRNAs, miRNAs, and lncRNAs in the prefrontal cortex of the mice in the 0 and 50 mg/kg PS NPs groups. The results revealed that mice exposed to chronic PS NPs developed depressive-like responses in a dose-dependent manner. It was demonstrated that 987 mRNAs, 29 miRNAs, and 116 lncRNAs were significantly different between the two groups. Then, a competing endogenous RNA (ceRNA) network containing 6 lncRNAs, 18 miRNAs, and 750 mRNAs was constructed. Enrichment results suggested that PS NPs may contribute to the onset of depression-like responses through the activation of axon guidance, neurotrophin-signaling pathways, and dopaminergic synapses. This study provided evidence of the molecular relationship between PS NPs and depression-like responses.

Background: Neonatal acute respiratory distress syndrome (ARDS) is a clinical disorder characterized by excessive acute inflammatory response in lung parenchyma and has high morbidity and mortality. However, the therapeutic treatments are still lacking. The aim of this study is to evaluate the role of unfractionated heparin in neonatal ARDS and explore the underlying mechanism of its effects. Methods: To conduct the ARDS model, the mouse pups were treated by intraperitoneal injection of lipopolysaccharide (LPS) (10 mg/kg). For unfractionated heparin intervention group, C57BL/6 mouse pups received a single subcutaneous injection of unfractionated heparin (400 IU/kg) 30 minutes prior to LPS. The survival rate was recorded for each group. Histological analysis was used to evaluate lung injury. MPO (myeloperoxidase) concentration level in lung tissues and extracellular histones in serum were detected by enzyme linked immunosorbent assay (ELISA). A commercially available kit was used to detect inflammatory cytokine levels in serum. Real time quantitative polymerase chain reaction (qPCR) and western blot were used to detect the mRNA and protein in the JAK2/STAT3 signaling pathway, respectively. Results: Intervention of unfractionated heparin significantly increased the survival rate of mouse pups with ARDS, restored lung architecture, inhibited neutrophil infiltration as evidenced by reduced MPO concentration, and attenuated the LPS-induced inflammatory responses, characterized by the down-regulation of proinflammatoy factors and up-regulation of anti-inflammatory factor when compared with the ARDS group. In addition, the concentration of extracellular histones, which have been proven to be mediated in the pathogenesis of ARDS, was diminished by unfractionated heparin. Moreover, the protein expressions of p-JAK2 (Y1007/1008) and p-STAT3 (Y705) in the ARDS group were remarkably up-regulated, which were reversed by unfractionated heparin. Conclusions: Unfractionated heparin protects LPS-induced ARDS via inhibiting JAK2/STAT3 pathway in neonatal mice, which might present a novel therapeutic target for ARDS of neonates.

Abstract Patients with type 2 diabetes mellitus (T2DM) have a higher risk to develop cognitive impairment. Several studies reported the potential roles of vitamin D in prevention of cognitive impairment, but the mechanism remains unclear. The present study aims to investigate the protective effects of vitamin D3 on cognitive impairment in db/db mice and to explore the possible mechanism. Twelve‐week‐old male db/db mice were randomly administrated with low, medium, and high dose of vitamin D3 (LVD, MVD, and HVD groups, respectively) and equivalent volume vitamin D3 solvent (corn oil, DM group) intragastrically. Eight age‐matched db/m mice were given equivalent volume corn oil as normal group. After 16 weeks of vitamin D3 treatment, the concentrations of fasting serum glucose in three vitamin D3 groups (especially the 1,000 IU/kg·bw dose) were significantly decreased compared with DM group. Pathology revealed that the neuron damage was reduced in vitamin D3 groups. MVD intervention significantly shortened the escape latency on day 5 and extended time in the target quadrant. Mice in HVD group had significantly higher exploration time and discrimination index compared with the DM group mice. Moreover, vitamin D3 treatment has increased the phosphorylation of cAMP‐response element‐binding protein and the expression of brain‐derived neurotrophic factor and vitamin D receptor. This treatment, meanwhile, has decreased the expression of tumor necrosis factor‐α, the phosphorylation of inhibitor kappa Bα (IκBα), and nuclear factor‐κB p65 (NF‐κB p65) in the hippocampus of db/db mice. These results suggest that vitamin D3 alleviated cognitive impairment in the hippocampus of db/db mice. Down‐regulation of the NF‐κB signaling pathway‐related proteins IκBα and p65 might be one of the possible mechanisms.

BackgroundNecrotizing enterocolitis (NEC) is the most prevalent gastrointestinal disorder that predominantly threatens preterm newborns. Succinate is an emerging metabolic signaling molecule that was recently studied in relation to the regulation of intestinal immunity and homeostasis. We aimed to investigate the relationship between NEC and gut luminal succinate and preliminarily explored the effect of succinate on NEC pathogenesis.MethodsFecal samples from human neonates and mouse pups were analyzed by HPLC – MS/MS and 16S rRNA gene sequencing. C57BL/6 mice were randomly divided into four groups: control, NEC, Lsuc, and Hsuc. The mortality, weight gain, and intestinal pathological changes in four mouse groups were observed. Inflammatory cytokines and markers of macrophages were identified by quantitative real-time PCR. Succinate receptor 1 (SUCNR1) localization was visualized by immunohistochemistry. The protein levels of SUCNR1 and hypoxia-inducible factor 1a (HIF-1a) were quantified by western blotting.ResultsThe levels of succinate in feces from NEC patients were higher than those in feces from non-NEC patients (P