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Most paleoclimate studies of Mainland Southeast Asia hydroclimate focus on the summer monsoon, with few studies investigating rainfall in other seasons. Here, we present a multiproxy stalagmite record (45,000 to 4,000 years) from central Vietnam, a region that receives most of its annual rainfall in autumn (September-November). We find evidence of a prolonged dry period spanning the last glacial maximum that is punctuated by an abrupt shift to wetter conditions during the deglaciation at ~14 ka. Paired with climate model simulations, we show that sea-level change drives autumn monsoon rainfall variability on glacial-orbital timescales. Consistent with the dry signal in the stalagmite record, climate model simulations reveal that lower glacial sea level exposes land in the Gulf of Tonkin and along the South China Shelf, reducing convection and moisture delivery to central Vietnam. When sea level rises and these landmasses flood at ~14 ka, moisture delivery to central Vietnam increases, causing an abrupt shift from dry to wet conditions. On millennial timescales, we find signatures of well-known Heinrich Stadials (HS) (dry conditions) and Dansgaard-Oeschger Events (wet conditions). Model simulations show that during the dry HS, changes in sea surface temperature related to meltwater forcing cause the formation of an anomalous anticyclone in the Western Pacific, which advects dry air across central Vietnam, decreasing autumn rainfall. Notably, sea level modulates the magnitude of millennial-scale dry and wet phases by muting dry events and enhancing wet events during periods of low sea level, highlighting the importance of this mechanism to autumn monsoon variability.

The outbreak of the COVID-19 pandemic results in the turning from offline teaching to online teaching. Students enjoy short videos and like barrage during the pandemic. We found that the introduction of barrage into online teaching is of great help to improve the students' attention and enthusiasm. In order to verify the correctness of this conjecture, we launched a questionnaire survey. According to the preliminary conclusions, we found that student's think that such adaption is not only interesting, but also can promote the interaction, and therefore improve the learning effect. It should conform to the trend of teaching development in the new era.

Aim The aim of this study was to purify proanthocyanidins from areca nut seeds (P-AN) and to investigate the bactericidal activity and mechanism of the purified products against Streptococcus mutans. Methods and results Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry, Fourier transform infrared, Matrix-assisted laser desorption/ ionization time of flight mass spectrometry (MADLI-TOF-MS), and thiolysis experiment were used for P-AN chemical analysis. Time-kill analysis and glycolytic pH drop were used to evaluate the activity of S. mutans in vitro. Meanwhile, the investigation of the bacteriostatic mechanism included membrane protein, fluidity, permeability, and integrity tests. The results showed that P-AN was a kind of proanthocyanidin mainly composed of B-type proanthocyanidins and their polymers. Moreover, MADLI-TOF-MS and thiolysis experiments demonstrated that the degree of polymerization of P-AN was 13. The time-kill analysis showed that P-AN had strong bactericidal activity against S. mutans. P-AN at minimum inhibitory concentration (MIC) concentrations was able to induce S. mutans death, while complete lethality occurred at 2 MIC. Glycolysis test showed that P-AN significantly inhibited S. mutans acid production (P  < .01). The morphological changes of S. mutans were observed by scanning electron microscopy and transmission electron microscopy experiments, which indicated that P-AN destroyed the cellular structure of S. mutans. At the same time, significant changes were observed in membrane proteins, fluidity, permeability, and integrity. Conclusion P-AN can effectively inhibit the activity of S. mutans. P-AN can reduce the erosion of the tooth surface by the acid of S. mutans. P-AN could break the structure of the cell membrane protein of S. mutans. P-AN could destroy the integrity of membrane, resulting in the death of S. mutans. [ABSTRACT FROM AUTHOR]

Patients with locally advanced head and neck squamous cell carcinoma (LA‐HNSCC) have poor survival outcomes. The real‐world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)‐based chemoradiotherapy in patients with LA‐HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3‐year overall survival (OS) rate. Log‐rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow‐up time was 54.2 (95% confidence interval [CI]: 52.7–55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57–0.99, p = 0.038) and progression‐free survival (PFS) (HR = 0.74, 95% CI: 0.58–0.96, p = 0.021). Subgroup analysis revealed that aged 50–60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab‐related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA‐HNSCC patients in an IMRT era. [ABSTRACT FROM AUTHOR]

Drug‐target interaction (DTI) prediction is essential for new drug design and development. Constructing heterogeneous network based on diverse information about drugs, proteins and diseases provides new opportunities for DTI prediction. However, the inherent complexity, high dimensionality and noise of such a network prevent us from taking full advantage of these network characteristics. This article proposes a novel method, NGCN, to predict drug‐target interactions from an integrated heterogeneous network, from which to extract relevant biological properties and association information while maintaining the topology information. It focuses on learning the topology representation of drugs and targets to improve the performance of DTI prediction. Unlike traditional methods, it focuses on learning the low‐dimensional topology representation of drugs and targets via graph‐based convolutional neural network. NGCN achieves substantial performance improvements over other state‐of‐the‐art methods, such as a nearly 1.0% increase in AUPR value. Moreover, we verify the robustness of NGCN through benchmark tests, and the experimental results demonstrate it is an extensible framework capable of combining heterogeneous information for DTI prediction. [ABSTRACT FROM AUTHOR]

With the development of the connected autonomous bus, the interactions between the bus and social vehicle during the mandatory lane changing for bus exiting become more diverse and complex. This research investigates the evolutionary dynamics of behavioral decision-making for the bus and social vehicle in different scenarios. The evolutionary game model for the connected autonomous bus and social vehicle is built, as do the human-driven bus and social vehicle, and the connected autonomous bus under different penetration rates and social vehicle. The results of numerical experiments reveal that the connected autonomous bus chooses to change lanes in most instances, and the strategies of the human-driven bus show conservative tendencies. Such tendencies are weakened when the connected autonomous bus and human-driven bus are mixed. As for the social vehicle in different scenarios, the strategies that balance overall traffic safety and efficiency are promoted. This research provides some references for intelligent decision-making of lane changing in urban public transportation., Author(s): Ronghan Yao [1]; Xiaojing Du (corresponding author) [1]; Wenyan Qi [1]; Li Sun [1] 1. Introduction Mandatory lane changing for bus exiting is one essential part in the daily [...]

The Asian summer monsoon (ASM) is teleconnected to the El Niño Southern Oscillation (ENSO), but this relationship is nonstationary and has shifted significantly in recent decades. Characterizing the drivers of such shifts is crucial for improving ASM prediction and extreme event preparedness. Paleoclimate records indicate a link between ASM strength and solar activity on multidecadal‐to‐centennial timescales, but 20th‐century data are too short to test mechanisms. Here we evaluate how solar irradiance influences the ASM‐ENSO relationship using last‐millennium paleoclimate data assimilation reconstructions and model simulations. We find that high solar irradiance weakens the ENSO‐East Asian summer monsoon (EASM) correlation, but strengthens the ENSO‐South Asian summer monsoon (SASM) correlation. Solar irradiance likely influences the strength of the ENSO‐EASM and ENSO‐SASM teleconnections via changes in the Western Pacific Subtropical High and the amplitude of ENSO events, respectively. We suggest a need for considering solar activity in decadal ASM rainfall predictions under global warming scenarios. Plain Language Summary: The Asian summer monsoon (ASM) affects over one‐third of the world's population, with significant environmental and economic impacts. The ASM is influenced by the El Niño Southern Oscillation (ENSO), but the ENSO‐ASM relationship has undergone notable changes in recent decades. Understanding the drivers of these changes is essential for improving ASM prediction. Previous studies based on individual records of past climate change have indicated a connection between ASM strength and solar activity over long periods, but 20th‐century instrumental data are too short to fully understand this link. In this study, we investigated the influence of solar activity on the ENSO‐ASM relationship using past climate records and model simulations spanning the last 1,000 years. We find that high solar irradiance weakens the ENSO‐East Asian summer monsoon relationship while strengthening the ENSO‐South Asian summer monsoon relationship. Solar irradiance might impact the strength of the ENSO‐ASM relationship by causing changes in the air pressure systems over the western Pacific and the intensity of ENSO events. These findings imply that solar activity, combined with global warming, will affect rainfall in the ASM region. It is crucial to consider solar activity in the long‐term prediction of ASM rainfall as the climate continues to warm. Key Points: Solar irradiance altered the El Niño‐Southern Oscillation (ENSO) and Asian summer monsoon relationship during the past millenniumHigh solar irradiance weakens (strengthens) the ENSO‐East Asian (South Asian) summer monsoon correlationSolar irradiance modulates the ENSO‐ASM teleconnection through changes in the Western Pacific Subtropical High and ENSO event amplitude [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are considered to play a key role in the development and progression of pancreatic ductal adenocarcinoma (PDAC). However, little is known about lipid metabolism reprogramming in PDAC CSCs. Here, we assigned stemness indices, which were used to describe and quantify CSCs, to every patient from the Cancer Genome Atlas (TCGA-PAAD) database and observed differences in lipid metabolism between patients with high and low stemness indices. Then, tumor-repopulating cells (TRCs) cultured in soft 3D (three-dimensional) fibrin gels were demonstrated to be an available PDAC cancer stem-like cell (CSLCs) model. Comprehensive transcriptome and lipidomic analysis results suggested that fatty acid metabolism, glycerophospholipid metabolism, and, especially, the sphingolipid metabolism pathway were mostly associated with CSLCs properties. SPHK1 (sphingosine kinases 1), one of the genes involved in sphingolipid metabolism and encoding the key enzyme to catalyze sphingosine to generate S1P (sphingosine-1-phosphate), was identified to be the key gene in promoting the stemness of PDAC. In summary, we explored the characteristics of lipid metabolism both in patients with high stemness indices and in novel CSLCs models, and unraveled a molecular mechanism via which sphingolipid metabolism maintained tumor stemness. These findings may contribute to the development of a strategy for targeting lipid metabolism to inhibit CSCs in PDAC treatment. [ABSTRACT FROM AUTHOR]

This study explores potential hypoglycemic mechanisms by preparing and identifying novel dipeptidyl peptidase IV (DPP‐IV) inhibitory peptides from goat milk (GM) whey protein. Papain was used to hydrolyze the GM whey protein. After purification by ultrafiltration, the Sephadex column, and preparative RP‐HPLC, the peptide inhibited DPP‐IV, α‐glucosidase, and α‐amylase with IC50 of 0.34, 0.37, and 0.72 mg/mL, respectively. To further explore the inhibitory mechanism of peptides on DPP‐IV, SPPEFLR, LDADGSY, YPVEPFT, and FNPTY were identified and synthesized for the first time, with IC50 values of 56.22, 52.16, 175.7, and 62.32 µM, respectively. Molecular docking and dynamics results show that SPPEFLR, LDADGSY, and FNPTY bind more tightly to the active pocket of DPP‐IV, which was consistent with the in vitro activity. Furthermore, the first three N‐terminals of SPPEFLR and FNPTY peptides exhibit proline characteristics and competitively inhibit DPP‐IV. Notably, the first N‐terminal leucine of LDADGSY may play a key role in inhibiting DPP‐IV. [ABSTRACT FROM AUTHOR]

Background and Aims: Leisure sedentary behavior (LSB) is associated with the risk of cancer, but the causal relationship between them has not been clarified. The aim of this study was to assess the potential causal association between LSB and risk of 15 site‐specific cancers. Methods: The causal association between LSB and cancer were assessed with univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR). 194 SNPs associated with LSB (from the UK Biobank 408,815 individuals) were adopted as the instrument variables. Sensitivity analyses were performed to ensure the robustness of the results. Results: UVMR analysis revealed that television watching significantly increased the risk of endometrial cancer (OR = 1.29, 95% CI = 1.02–1.64, p = 0.04) (mainly the endometrioid histology [OR = 1.28, 95% CI = 1.02–1.60, p = 0.031])，breast cancer (OR = 1.16, 95% CI = 1.04–1.30, p = 0.007) (both ER+ breast cancer [OR = 1.17, 95% CI = 1.03–1.33, p = 0.015], and ER− breast cancer [OR = 1.55, 95% CI = 1.26–1.89, p = 2.23 × 10−5]). Although causal association was not found between television watching and ovarian cancer, it was seen in low grade and low malignant potential serous ovarian cancer (OR = 1.49, 95% CI = 1.07–2.08, p = 0.018). However, significant results were not obtained in the UVMR analysis between driving, computer use and the 15 types of cancer. Further MVMR analysis indicated that the above results are independent from most metabolic factors and dietary habits, but mediated by educational attainment. Conclusion: LSB in form of television watching has independent causal association with the risk of endometrial cancer, breast cancer, and ovarian cancer. [ABSTRACT FROM AUTHOR]