Metabolic pathways that mediate the effects of food deprivation on reproductive behavior in female Drosophila melanogaster.

In most species studied, energy deficits inhibit female reproductive behavior, but the location and nature of energy sensors and how they affect behavior are unknown. Progress has been facilitated by using Drosophila melanogaster, a species in which reproduction and food availability are closely linked. Adult males and females were either fed or food deprived (FD) and tested in an arena with a fed, opposite-sex conspecific with no food in the testing arena. Only FD females (not FD males) significantly decreased their copulation rate and increased their copulation latency, and the effects of FD were prevented in females fed either yeast alone or glucose alone, but not sucralose alone, cholesterol alone, or amino acids alone. It is well-known that high-fat diets inhibit copulation rate in this species, and the effects of FD on copulation rate were mimicked by treatment with an inhibitor of glucose but not free fatty acid oxidation. The availability of oxidizable glucose was a necessary condition for copulation rate in females fed either yeast alone or fed a nutritive fly medium, which suggests that the critical component of yeast for female copulation rate is oxidizable glucose. Thus, female copulation rate in D. melanogaster is sensitive to the availability of oxidizable metabolic fuels, particularly the availability of oxidizable glucose or substrates/byproducts of glycolysis.

DMF as an amine source: iron-catalyzed cyclization of 2H-azirines to imidazoles.

A novel method has been developed for the synthesis of 1-methyl-4,5-diaryl-1H-imidazoles through Fe(II)-catalyzed cyclization of 2H-azirines and N,N-dimethylformamide (DMF) as an amine source. This transformation involves the cleavage of C-N and CN double bonds and the construction of new C-N and CN double bonds. The reaction has readily available starting materials, a wide range of substrates and mild reaction conditions. In addition, the reaction also facilitated the convenient synthesis of 1-methyl-2,4,5-triaryl-1H-imidazoles.

Large-range lithography nano-alignment without phase unwrapping by a dual-frequency moiré fringe heterodyne.

Moiré fringe is an effective approach to realize nano-alignment. However, affected by short periodicity and phase unwrapping, moiré fringe technology has small alignment ranges and redundant algorithms, making it difficult to meet practical application requirements. To solve the problem, we propose a large-range lithography nano-alignment method without phase unwrapping by a dual-frequency moiré fringe heterodyne. This method obtains four sets of moiré fringes from the main and differential alignment marks and then calculates the misalignment information using the heterodyne method. In this approach, both large alignment range and high alignment accuracy are achieved while avoiding the phase unwrapping process. The experimental results verified the rationality and feasibility of the proposed method.

The influence of cognitive ability in Chinese reading comprehension: can working memory updating change Chinese primary school students' reading comprehension performance?

With the development of educational cognitive neuroscience, language instruction is no longer perceived as mechanical teaching and learning. Individual cognitive proficiency has been found to play a crucial role in language acquisition, particularly in the realm of reading comprehension. The primary objective of this study was to investigate two key aspects: firstly, to assess the predictive effects of the central executive (CE) on the Chinese reading comprehension scores of Chinese primary school students, and secondly, to explore the influence of CE training on the Chinese reading comprehension performance of Chinese primary school students. Chinese primary school students were recruited as participants. Experiment 1 used a Chinese N-back task, a Chinese Stroop task, and a number-pinyin conversion task to investigate the predictive effect of the CE components on Chinese reading comprehension. Experiment 2, based on the results of Experiment 1, used the Chinese character N-back training to explore the influence of updating training on Chinese reading comprehension. The findings from Experiment 1 underscored that CE had a predictive effect on Chinese reading comprehension scores. And updating had a prominent role in it. Experiment 2 revealed that the experimental group exhibited an enhancement in their updating performance following N-back training. Although the reading comprehension performance of the two groups after training did not produce significant differences in total scores, the experimental group showed maintained and higher microscopic reading comprehension scores than the control group in the more difficult post-test. In summary, this study yields two primary conclusions: (1) CE was able to predict Chinese reading comprehension scores. Updating has an important role in prediction. (2) Updating training enhances students' updating performance and positively influences students' Chinese microscopic reading comprehension performance.

Design, synthesis, and evaluation of BTK-targeting PROTACs with optimized bioavailability in vitro and in vivo.

Ibrutinib is a first-line drug for the treatment of B-cell malignancies. BTKC481S mutation has led to drug resistance during clinical application. Herein, a novel BTK-targeting PROTAC molecule with better solubility and bioavailability was developed. Compound 15-271 has better solubility than ibrutinib and some reported BTK PROTACs. 15-271 has better liver microsomal stability than its analogues in multiple species. More importantly, 15-271 has a longer half-life and better bioavailability in vivo. The development strategy of compound 15-271 can be a general procedure for the optimization of other PROTACs.

The effect of working memory updating training on the Chinese writing ability of primary school students.

Objective: This study aimed to explore the effects of working memory updating training on primary school students' writing ability and performance. Methods: A total of 46 fourth-grade Chinese primary school students were recruited; their performance in the Chinese character N-back training task, the Writing Ability Questionnaire, and a time-limited writing task was assessed. Results: The paired-sample t-test revealed that working memory updating training significantly improved the experimental group's working memory level. After training, a repeated measures ANOVA revealed that the experimental group's performance on the Writing Ability Questionnaire improved and was higher than that of the control group. In the time-limited writing task, independent-sample t-tests revealed that the experimental group's writing fluency increased and was higher than that of the control group, while the latter's grammatical accuracy and complexity decreased and were lower than those of the former. Conclusion: Working memory updating training can be used as auxiliary cognitive training to improve primary school students' working memory level, thereby promoting their writing development.

Comment on "Isolating Polaritonic 2D-IR Transmission Spectra".

This Viewpoint responds to the analysis of 2D IR spectra of vibration cavity polaritons in the study reported in The Journal of Physical Chemistry Letters (Duan et al. 2021, 12, 11406). That report analyzed 2D IR spectra of strongly coupled molecules, such as W(CO)6 and nitroprusside anion, based on subtracting a background signal generated by polariton filtered free space signals. They assigned the resulting response as being due to excited polaritons. We point out in this Viewpoint that virtually all of the response can be properly reproduced using the physics of transmission through an etalon containing a material modeled with a complex dielectric function describing the ground- and excited-state absorber populations. Furthermore, such a coupled system cannot be described as a scaled sum of the bare molecular and cavity responses.

Information cocoons in online navigation.

Social media and online navigation bring us enjoyable experiences in accessing information, and simultaneously create information cocoons (ICs) in which we are unconsciously trapped with limited and biased information. We provide a formal definition of IC in the scenario of online navigation. Subsequently, by analyzing real recommendation networks extracted from Science, PNAS, and Amazon websites, and testing mainstream algorithms in disparate recommender systems, we demonstrate that similarity-based recommendation techniques result in ICs, which suppress the system navigability by hundreds of times. We further propose a flexible recommendation strategy that addresses the IC-induced problem and improves retrieval accuracy in navigation, which are demonstrated by simulations on real data and online experiments on the largest video website in China. This paper quantifies the challenge of ICs in recommender systems and presents a viable solution, which offer insights into the industrial design of algorithms, future scientific studies, as well as policy making.

Enabling multiple intercavity polariton coherences by adding quantum confinement to cavity molecular polaritons.

In this study, the "particle in a box" idea, which was broadly developed in semiconductor quantum dot research, was extended into mid-infrared (IR) cavity modes by applying lateral confinement in an optical cavity. The discrete cavity modes hybridized with molecular vibrational modes, resulting in a quartet of polariton states that can support multiple coherence states in the IR regime. We applied tailored pump pulse sequences to selectively prepare these coherences and verified the multi-coherence existence. The simulation based on Lindblad equation showed that because the quartet of polariton states resided in the same cavity, they were specifically robust toward decoherence caused by fluctuations in space. The multiple robust coherences paved the way for entangled states and coherent interactions between cavity polaritons, which would be critical for advancing polariton-based quantum information technology.

Metabolomics of Extracellular Vesicles: A Future Promise of Multiple Clinical Applications.

Extracellular vesicles (EVs) can contain DNA, RNA, proteins and metabolic molecules from primary origins; they are coated with a phospholipid bilayer membrane and released by cells into the extracellular matrix. EVs can be obtained from various body liquids, including the blood, saliva, cerebrospinal fluid, and urine. As has been proved, EVs-mediated transfer of biologically active molecules is crucial for various physiological and pathological processes. Extensive investigations have already begun to explore the diagnosis and prognosis potentials for EVs. Furthermore, research has continued to recognize the critical role of nucleic acids and proteins in EVs. However, our understanding of the comprehensive effects of metabolites in these nanoparticles is currently limited and in its infancy. Therefore, we have attempted to summarize the recent research into the metabolomics of EVs in relation to potential clinical applications and discuss the problems and challenges that have occurred, to provide more guidance for the future development in this field.

Phospholipid-Membrane-Based Nanovesicles Acting as Vaccines for Tumor Immunotherapy: Classification, Mechanisms and Applications.

Membrane vesicles, a group of nano- or microsized vesicles, can be internalized or interact with the recipient cells, depending on their parental cells, size, structure and content. Membrane vesicles fuse with the target cell membrane, or they bind to the receptors on the cell surface, to transfer special effects. Based on versatile features, they can modulate the functions of immune cells and therefore influence immune responses. In the field of tumor therapeutic applications, phospholipid-membrane-based nanovesicles attract increased interest. Academic institutions and industrial companies are putting in effort to design, modify and apply membrane vesicles as potential tumor vaccines contributing to tumor immunotherapy. This review focuses on the currently most-used types of membrane vesicles (including liposomes, bacterial membrane vesicles, tumor- and dendritic-cell-derived extracellular vesicles) acting as tumor vaccines, and describes the classification, mechanism and application of these nanovesicles.

Cavity-enabled enhancement of ultrafast intramolecular vibrational redistribution over pseudorotation.

Vibrational strong coupling (VSC) between molecular vibrations and microcavity photons yields a few polaritons (light-matter modes) and many dark modes (with negligible photonic character). Although VSC is reported to alter thermally activated chemical reactions, its mechanisms remain opaque. To elucidate this problem, we followed ultrafast dynamics of a simple unimolecular vibrational energy exchange in iron pentacarbonyl [Fe(CO)5] under VSC, which showed two competing channels: pseudorotation and intramolecular vibrational-energy redistribution (IVR). We found that under polariton excitation, energy exchange was overall accelerated, with IVR becoming faster and pseudorotation being slowed down. However, dark-mode excitation revealed unchanged dynamics compared with those outside of the cavity, with pseudorotation dominating. Thus, despite controversies around thermally activated VSC modified chemistry, our work shows that VSC can indeed alter chemistry through a nonequilibrium preparation of polaritons.

Effect of Insoles Treatment on School-Age Children with Symptomatic Flexible Flatfoot: A 2-Year Follow-Up Study.

Background: Flatfoot is common among children. Symptomatic flexible flatfoot is one of the various types which needs treatment. Wearing insoles is considered one of the conservative therapies, but its effects are still uncertain. This study aims to provide evidence for the efficacy of insoles treatment among school-aged children with symptomatic flexible flatfoot. Methods: Patient who were Children who were diagnosed with symptomatic flexible flatfoot and received insoles treatment in authors' institute were retrospectively included. Their ages, body mass index, pain positions, pain frequency, valgus angle, arch index and visual analogue scale (VAS) score were collected before and after insole treatment. Results: A total of 32 children were included in this study. The results showed that wearing insoles for 2 years caused a significant improvement in pain frequency, valgus angle, arch index and VAS score. Conclusions: This study indicated that pediatric symptomatic flexible flatfoot could be relieved by wearing insoles for 2 years. Insole treatment might be a workable option for pediatric symptomatic flexible flatfoot in children older than 6 years old.

Treatment of Pediatric Intercondylar Humerus Fracture With External Fixation and Percutaneous Pinning After Closed Reduction.

Background: It is uncommon for young children to suffer an intercondylar fracture of the distal humerus. Although many approaches have been described to manage, there is no specific and accepted treatment protocol for such fracture patterns. This study aimed to identify the incidence of intercondylar fracture of the distal humerus in the pediatric population and report the clinical outcome of external fixation and percutaneous pinning in such injury patterns. Methods: Pediatric patients under the age of 14 years who had an intercondylar fracture of the distal humerus treated with external fixation and percutaneous pinning between January 2013 and December 2018 at the author's Wuhan Union Hospital were retrospectively evaluated. The detailed baseline information of the patients, operating time, time to union time, and carrying angle difference (CAD) of the injured extremity were collected. During the follow-up visit, clinical results were evaluated using the Mayo Elbow Performance Score (MEPS) and the Flynn criteria. Results: A total of eight patients (2 women and 6 men) with an average age of 8 years (5-12 years) who had an intercondylar fracture of the distal humerus (1 C2 and 7 C1) were included. All the patients achieved union, and the average MEPS score was 95 points 24 months after the surgery. Conclusion: The intercondylar fracture of the distal humerus in children is rare, and closed reduction and external fixation is a viable treatment option, especially for the C1 type of fracture pattern.

Engineered extracellular vesicles: potentials in cancer combination therapy.

Extracellular vesicles (EVs) are a group of secretory vesicles with cell-derived membrane and contents. Due to the cargo delivery capability, EVs can be designed as drug delivery platforms for cancer therapy. Biocompatibility and immune compatibility endow EVs with unique advantages compared with other nanocarriers. With the development of this field, multiple ingenious modification methods have been developed to obtain engineered EVs with desired performance. Application of engineered EVs in cancer therapy has gradually shifted from monotherapy to combinational therapy to fight against heterogeneous cancer cells and complex tumor microenvironment. In addition, the strong plasticity and load capacity of engineered EV make it potential to achieve various combinations of cancer treatment methods. In this review, we summarize the existing schemes of cancer combination therapy realized by engineered EVs, highlight the mechanisms and representative examples of these schemes and provide guidance for the future application of engineered EVs to design more effective cancer combination treatment plans.

Discovery of an insulin-induced gene binding compound that ameliorates nonalcoholic steatohepatitis by inhibiting sterol regulatory element-binding protein-mediated lipogenesis.

BACKGROUND AND AIMS: NASH is associated with high levels of cholesterol and triglyceride (TG) in the liver; however, there is still no approved pharmacological therapy. Synthesis of cholesterol and TG is controlled by sterol regulatory element-binding protein (SREBP), which is found to be abnormally activated in NASH patients. We aim to discover small molecules for treating NASH by inhibiting the SREBP pathway. APPROACH AND RESULTS: Here, we identify a potent SREBP inhibitor, 25-hydroxylanosterol (25-HL). 25-HL binds to insulin-induced gene (INSIG) proteins, stimulates the interaction between INSIG and SCAP, and retains them in the endoplasmic reticulum, thereby suppressing SREBP activation and inhibiting lipogenesis. In NASH mouse models, 25-HL lowers levels of cholesterol and TG in serum and the liver, enhances energy expenditure to prevent obesity, and improves insulin sensitivity. 25-HL dramatically ameliorates hepatic steatosis, inflammation, ballooning, and fibrosis through down-regulating the expression of lipogenic genes. Furthermore, 25-HL exhibits both prophylactic and therapeutic efficacies of alleviating NASH and atherosclerosis in amylin liver NASH model diet-treated Ldlr-/- mice, and reduces the formation of cholesterol crystals and associated crown-like structures of Kupffer cells. Notably, 25-HL lowers lipid contents in serum and the liver to a greater extent than lovastatin or obeticholic acid. 25-HL shows a good safety and pharmacokinetics profile. CONCLUSIONS: This study provides the proof of concept that inhibiting SREBP activation by targeting INSIG to lower lipids could be a promising strategy for treating NASH. It suggests the translational potential of 25-HL in human NASH and demonstrates the critical role of SREBP-controlled lipogenesis in the progression of NASH by pharmacological inhibition.

Workplace Violence, Workforce Stability, and Well-being in China's Psychiatric Hospitals.

INTRODUCTION: Workplace violence against psychiatric professionals is a growing problem, yet nationally representative data in China are lacking. This study examines workplace violence against psychiatrists and psychiatric nurses in China as well as its association with workforce stability and well-being . METHODS: Data came from a 2019 national survey of 14,264 participants (including 4,520 psychiatrists and 9,744 nurses) from 41 psychiatric hospitals across China. The occurrence of physical and verbal assaults among psychiatrists and psychiatric nurses was reported. Logistic regression models were constructed to examine the participants' characteristics associated with encountering workplace violence and the association of encountering violence with self-reported quality of life, health status, turnover intention, and career satisfaction. Analyses were performed during 2020. RESULTS: In 2019, among 14,264 psychiatrists and psychiatric nurses in China, 81% reported encountering workplace violence during the past year. Psychiatrists were 0.68 (95% CI=0.55, 0.83) times less likely to report an encounter of violence than nurses. Male and younger nurses were 2.20 (95% CI=1.72, 2.81) and 1.21 (95% CI=1.01, 1.45) times more likely to report violence. Psychiatrists who had a higher educational degree or a higher professional rank were more vulnerable to violence. Encountering violence was significantly associated with poor quality of life, less satisfaction with health status, greater intention to leave the current job, and career dissatisfaction. CONCLUSIONS: Workplace violence against psychiatrists and psychiatric nurses are common in China, indicating that China's psychiatric professionals are facing a significant threat to occupational safety. To maintain psychiatric workforce stability, actions are needed to reduce the prevalence of workplace violence at the system, institutional, and individual levels.

Interleukin -1ß Promotes Lung Adenocarcinoma Growth and Invasion Through Promoting Glycolysis via p38 Pathway.

BACKGROUND: There is a close relationship among inflammation, glycolysis, and tumors. The IL-1 family includes important inflammatory cytokines, among which IL-1ß has been widely studied. In this study, we focused on the effect of IL-1ß on glycolysis of lung adenocarcinoma (LUAD) cells in vivo and in vitro and explored its possible mechanisms. METHODS: A bioinformatic database and quantitative real-time PCR were used to analyze the expression of glycolysis-related enzyme genes and their correlations with IL1ß in human LUAD samples. The human LUAD cell line A549 and Lewis lung carcinoma LLC cell line were stimulated with IL-1ß. In vitro treatment effects, including glycolysis level, migration, and invasion were evaluated with a glucose assay kit, lactate assay kit, Western blotting, wound healing, and the transwell method. We established a mouse model of subcutaneous tumors using LLC cells pretreated with IL-1ß and analyzed in vivo treatment effects through positron-emission tomography-computed tomography and staining. Virtual screening and molecular dynamic simulation were used to screen potential inhibitors of IL-1ß. RESULTS: Our results showed that IL1ß was positively correlated with the expression of glycolysis-related enzyme genes in LUAD. Glycolysis, migration, and invasion significantly increased in A549 and LLC stimulated with IL-1ß. In vivo, IL-1ß increased growth, mean standard uptake value, and pulmonary tumor metastasis, which were inhibited by the glycolysis inhibitor 2-deoxy-D-glucose and p38-pathway inhibitors. Small molecular compound ZINC14610053 was suggested being a potential inhibitor of IL-1ß. CONCLUSION: IL-1ß promotes glycolysis of LUAD cells through p38 signaling, further enhancing tumor-cell migration and invasion. These results show that IL-1ß links inflammation to glycolysis in LUAD, and targeting IL-1ß and the glycolysis pathway may be a potential therapeutic strategy for lung cancer.

Strategies for Constructing College Students' Entrepreneurial Value Judgments Based on Educational Psychology.

Against the background of economic globalization, the strategies for constructing college students' entrepreneurial value judgment are explored, providing college graduates with more employment options and thereby keeping up with the trend of the times. The documentary analysis and questionnaire survey methods are adopted to investigate contemporary college students' entrepreneurial value judgments, and the investigation results are organized. According to documentary materials, the discovered problems are analyzed to put forward strategies for constructing college students' entrepreneurial value judgments based on educational psychology. Results show that only 14.1% of college graduates choose to start a business; 48.7% do not understand or recognize the entrepreneurial values; 14.8% believe teaching activities on constructing entrepreneurial value judgments are insufficient, and the entrepreneurial atmosphere is lacking. Regarding the above investigation results, strategies for constructing college students' entrepreneurial value judgments are proposed, involving the construction environment, construction system, construction method, and construction mechanism. Hence, considering contemporary college students' entrepreneurial values, the proposed strategies for constructing college students' entrepreneurial judgments are suitable and valuable, providing a practical reference for enriching and perfecting the college innovation and entrepreneurship education systems.