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In the field of higher education, there are two dominant strands of interpretation of criticality, either as a decontextualized skill of logical reasoning, or a sense of action within larger contexts more than mere cognition. This research offers a reclaiming and reimagining of criticality in universities as an affective process, highlighting the entanglement of social, discursive and material perspectives. This research takes a comparative lens to investigate undergraduate students' perceptions of criticality and institutional cultivation of it in a Sociology undergraduate degree in China and the UK, adopting a qualitative interview method. Differences were found between cultures regarding the level of engagement with a range of criticality-embedded practices, including field work, critical inquiry in class, group work, etc. Through the development of criticality in various activities, students' feelings towards it shifted with contexts. While placed within physical and discursive universities that convey a sense of professionalism, students in the study acknowledged the importance of criticality and proactively demonstrated it. However, the feeling towards showcasing criticality outside campus was two-fold. Whereas criticality can be associated with negativity in social interactions, its value is appreciated as it enabled students to reconstruct their identities into a more rational, tolerant and caring one.

Abstract There remains a critical need for the precise control of CRISPR (clustered regularly interspaced short palindromic repeats)-based technologies. Here, we engineer a set of inducible CRISPR-based tools controllable by focused ultrasound (FUS), which can penetrate deep and induce localized hyperthermia for transgene activation. We demonstrate the capabilities of FUS-inducible CRISPR, CRISPR activation (CRISPRa), and CRISPR epigenetic editor (CRISPRee) in modulating the genome and epigenome. We show that FUS-CRISPR-mediated telomere disruption primes solid tumours for chimeric antigen receptor (CAR)-T cell therapy. We further deliver FUS-CRISPR in vivo using adeno-associated viruses (AAVs), followed by FUS-induced telomere disruption and the expression of a clinically validated antigen in a subpopulation of tumour cells, functioning as “training centers” to activate synthetic Notch (synNotch) CAR-T cells to produce CARs against a universal tumour antigen to exterminate neighboring tumour cells. The FUS-CRISPR(a/ee) toolbox hence allows the noninvasive and spatiotemporal control of genomic/epigenomic reprogramming for cancer treatment.

Introduction: Orthodontic tooth movement (OTM) involves complex interactions between mechanical forces and periodontal tissue adaptation, mainly mediated by periodontal ligament cells, including periodontal ligament stem cells (PDLSCs), osteoblasts, and osteoclasts. Dopamine (DA), a neurotransmitter known for its critical role in bone metabolism, is investigated in this study for its potential to enhance osteogenic differentiation in PDLSCs, which are pivotal in OTM. This study examined the potential of DA to facilitate OTM by binding to DA receptors (D1R and D2R) and activating the ERK1/2 signaling pathway. We propose that DA's interaction with these receptors on PDLSCs could enhance osteogenic differentiation, thereby accelerating bone remodeling and reducing the duration of orthodontic treatments, which offering a novel approach to improve clinical outcomes in orthodontic care. Methods: This study utilized a rat OTM model, micro-CT, histological analyses, and in vitro assays to investigate dopamine's effect on osteogenesis. PDLSCs were cultured and treated with DA, and cytotoxicity, osteogenic differentiation, gene and protein expression assessed. Results: Dopamine administration significantly increased trabecular bone density and osteogenic marker expression in an OTM rat model. In vitro, DA at 10 nM optimally promoted human PDLSCs osteogenesis without affecting proliferation. Blocking DA receptors or inhibiting the ERK1/2 pathway attenuated these effects, underscoring the importance of dopaminergic signaling in tension-induced osteogenesis during OTM. Conclusion: Taken together, our study reveals that local dopamine administration at a concentration of 10 nM not only enhances tension-induced osteogenesis in vivo but also significantly promotes osteogenic differentiation of PDLSCs in vitro through D1 and D2 receptor-mediated ERK1/2 signaling pathway activation.

Abstract The complexities encountered in microbial metabolic engineering continue to elude prediction and design. Unravelling these complexities requires strategies that go beyond conventional genetics. Using multiplex mutagenesis with double stranded (ds) DNA, we extend the multiplex repertoire previously pioneered using single strand (ss) oligonucleotides. We present ReaL-MGE (Recombineering and Linear CRISPR/Cas9 assisted Multiplex Genome Engineering). ReaL-MGE enables precise manipulation of numerous large DNA sequences as demonstrated by the simultaneous insertion of multiple kilobase-scale sequences into E. coli, Schlegelella brevitalea and Pseudomonas putida genomes without any off-target errors. ReaL-MGE applications to enhance intracellular malonyl-CoA levels in these three genomes achieved 26-, 20-, and 13.5-fold elevations respectively, thereby promoting target polyketide yields by more than an order of magnitude. In a further round of ReaL-MGE, we adapt S. brevitalea to malonyl-CoA elevation utilizing a restricted carbon source (lignocellulose from straw) to realize production of the anti-cancer secondary metabolite, epothilone from lignocellulose. Multiplex mutagenesis with dsDNA enables the incorporation of lengthy segments that can fully encode additional functions. Additionally, the utilization of PCR to generate the dsDNAs brings flexible design advantages. ReaL-MGE presents strategic options in microbial metabolic engineering.

Abstract Purpose This study aimed to determine the current turnover intention among workers at Centers for Disease Control and Prevention (CDCs) in Northeast China and to investigate the factors contributing to this phenomenon. Materials and methods The cross-sectional study was conducted in May 2023 across four northeastern provinces of China. The study included a total of 11,912 valid participants who were CDC workers selected using a stratified cluster sampling method. The study assessed demographics, turnover intention, work resources, work perceptions, and psychological support through online questionnaires. The binary logistic regression analysis identified the factors associated with turnover intention for CDC workers, while the Interpretative Structural Modelling (ISM) revealed the hierarchical relationship between the influencing factors. Results The study found that 28.8% of the respondents reported high turnover intention. The binary logistic regression suggested that the risk factors of turnover intention among employees included gender, age, education, and several work-related, organizational, and psychological factors. The work-related factors were daily working hours, job burnout, and role overload. The organizational factor was unit support for training, unit’s infrastructure conditions, leadership style, remuneration package and performance appraisal and promotion system. The psychological support factors were family support, professional identity, and organizational commitment. The ISM analysis results showed that the primary factors influencing CDC workers’ intention to leave were internally connected and grouped into four categories according to their level of impact: surface, transition, deep, and essential factors. Notably, the essential factors were professional identity and organizational commitment. Conclusion Nearly one-third of the respondents expressed a strong desire to resign from their employment. Turnover intention among CDC workers was subject to diverse influences. Early identification, detection, and targeted multidisciplinary interventions should be introduced to address the array of factors that affect staff, with particular emphasis on boosting the professional identity and organizational commitment of CDC workers.

Abstract Small extracellular vesicles (sEV) have emerged as a novel mode of intercellular material transport and information transmission. It has been suggested hormones may regulate the production and function of sEV. However, the specific impact of growth hormone-releasing hormone (GHRH) on pituitary sEV production and the role of sEV in the regulation of the GHRH-GH-IGF axis has not been previously reported. The results of the present study demonstrated that GHRH increased the production of pituitary sEV by promoting the expression of Rab27a. More importantly, GHRH induced alterations in protein and miRNA levels within GH3-sEV components. Notably, GH3-sEV with GHRH treatment exhibited the enhanced ability to impede BRL 3A cell proliferation and the expression of IGF-1. Conclusively, for the first time, we corroborate the influence of GHRH on pituitary sEV, thereby presenting novel evidence for how sEV participates in the balance of the GHRH-GH-IGF axis. Importantly, this study provides new insight into a novel balance mechanism mediated by sEV within the endocrine system. Graphical Abstract

Abstract Background Blood lipid profiles are associated with various nutritional elements and dietary factors. This study aimed to explore the association between total dietary vitamin E intake and remnant cholesterol (RC), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) using data from the National Health and Nutrition Examination Survey (NHANES). Methods A cross-sectional analysis was conducted using NHANES 2007–2018 data. A total of 8,639 eligible participants (45.58% men and 54.42% women) with an average age of 46.12 ± 16.65 years were included in this study. Weighted multivariate linear regression and subgroup analyses were used to examine the association between vitamin E intake and RC, TC, HDL-C, and LDL-C. Smooth curve fitting was used to explore potential non-linear associations. Results After adjusting for other covariates, multivariate linear regression analysis showed that higher vitamin E intake was negatively associated with plasma RC (β = -0.22, 95% CI: -0.27, -0.16), TC (β = -0.33, 95% CI: -0.51, -0.16), LDL-C (β = -0.25, 95% [confidence interval] CI: -0.40, -0.10) and positively associated with HDL-C (β = 0.13, 95% CI: 0.07, 0.20) in US adults. Subgroup analysis indicated that age may influence the association between vitamin E intake and RC. At the same time, gender may also affect the association between vitamin E intake and HDL-C. Conclusion Higher vitamin E intake was negatively associated with plasma RC, TC, LDL-C and positively associated with HDL-C.

Abstract We present a new scheme for Majorana modes in systems with nonsymmorphic-symmetry-protected band degeneracy. We reveal that when the gapless fermionic excitations are encoded with conventional superconductivity and magnetism, which can be intrinsic or induced by proximity effect, topological superconductivity and Majorana modes can be obtained. We illustrate this outcome in a system which respects the space group P4/n m m and features a fourfold-degenerate fermionic mode at (π, π) in the Brillouin zone. We show that in the presence of conventional superconductivity, different types of topological superconductivity, i.e., first-order and second-order topological superconductivity, with coexisting fragile Wannier obstruction in the latter case, can be generated in accordance with the different types of magnetic orders; Majorana modes are shown to exist on the boundary, at the corner and in the vortices. To further demonstrate the effectiveness of our approach, another example related to the space group P4/n c c based on this scheme is also provided. Our study offers insights into constructing topological superconductors based on bulk energy bands and conventional superconductivity and helps to find new material candidates and design new platforms for realizing Majorana modes.

Abstract We present a theory for charge-4e superconductivity as a leading low-temperature instability with a nontrivial d-wave symmetry. We show that in several microscopic models for the pair-density-wave (PDW) state, when the PDW wave vectors connect special parts of the Fermi surface, the predominant interaction is in the bosonic pairing channel mediated by exchanging low-energy fermions. This bosonic pairing interaction is repulsive in the s-wave channel but attractive in the d-wave one, leading to a d-wave charge-4e superconductor. By analyzing the Ginzburg-Landau free energy including higher-order fluctuation effects of PDW, we find that the charge-4e superconductivity emerges as a vestigial order of PDW, and sets in via a first-order transition. Both the gap amplitude and the transition temperature decay monotonically with increasing superfluid stiffness of the PDW order. Our work provides a microscopic mechanism of higher-charge condensates with unconventional ordering symmetry in strongly-correlated materials.

Relation extraction, as a key task in natural language processing, plays a significant role in deepening language understanding, constructing knowledge graphs, and optimizing information retrieval systems. However, traditional supervised learning methods are not well-suited for real-world scenarios due to the continuous emergence of new relations and the lack of large annotated datasets. Although the advent of large language models has significantly improved the performance of many natural language processing tasks, they still cannot effectively address the challenges of few-shot continual relation extraction. To fully leverage the semantic knowledge of large language models to mitigate catastrophic forgetting and overfitting issues, a novel few-shot continual relation extraction method, LAFA (large language model augmentation and feature alignment), is proposed. This method enhances representation alignment through various strategies such as relation instance rewriting, semantic expansion, and enhanced relation representation. It effectively improves the model adaptability to new relations and the retention of old knowledge while maintaining low data and computational costs. Experimental validation on two relation extraction datasets, FewRel and TACRED, demonstrates that LAFA outperforms existing methods in few-shot continual relation extraction tasks, particularly achieving the best results in incremental stages. Ablation experiments further reveal the significant contributions of each module to overall performance. Moreover, the inference efficiency and cost of LAFA are substantially lower than those of existing large language model-based methods, and it boasts strong scalability, being able to adapt to various language models.

Abstract In order to facilitate cardiovascular research to develop non-invasive optical heart pacing methods, we have generated a double-transgenic Drosophila melanogaster (fruit fly) model suitable for optogenetic pacing. We created a fly stock with both excitatory H134R-ChR2 and inhibitory eNpHR2.0 opsin transgenes. Opsins were expressed in the fly heart using the Hand-GAL4 driver. Here we describe Hand > H134R-ChR2; eNpHR2.0 model characterization including bi-directional heart control (activation and inhibition) upon illumination of light with distinct wavelengths. Optical control and real-time visualization of the heart function were achieved non-invasively using an integrated light stimulation and optical coherence microscopy (OCM) system. OCM produced high-speed and high-resolution imaging; simultaneously, the heart function was modulated by blue (470 nm) or red (617 nm) light pulses causing tachycardia, bradycardia and restorable cardiac arrest episodes in the same animal. The irradiance power levels and illumination schedules were optimized to achieve successful non-invasive bi-directional heart pacing in Drosophila larvae and pupae.

Abstract Background RNA sequencing (RNA-Seq) offers profound insights into the complex transcriptomes of diverse biological systems. However, standard differential expression analysis pipelines based on DESeq2 and edgeR encounter challenges when applied to the immediate early transcriptomes of Chlamydia spp., obligate intracellular bacteria. These challenges arise from their reliance on assumptions that do not hold in scenarios characterized by extensive transcriptomic activation and limited repression. Results Standard analyses using unique chlamydial RNA-Seq reads alone identify nearly 300 upregulated and about 300 downregulated genes, significantly deviating from actual RNA-Seq read trends. By incorporating both chlamydial and host reads or adjusting for total sequencing depth, the revised normalization methods each detected over 700 upregulated genes and 30 or fewer downregulated genes, closely aligned with observed RNA-Seq data. Further validation through qRT-PCR analysis confirmed the effectiveness of these adjusted approaches in capturing the true extent of transcriptomic activation during the immediate early phase of chlamydial infection. Conclusions This study highlights the limitations of standard RNA-Seq analysis tools in scenarios with extensive transcriptomic activation, such as in Chlamydia spp. during early infection. Our revised normalization methods, incorporating host reads or total sequencing depth, provide a more accurate representation of gene expression dynamics. These approaches may inform similar adjustments in other systems with unbalanced gene expression dynamics, enhancing the accuracy of transcriptomic analysis.

River basin water supplies are changing significantly as a result of global climate change. Therefore, it is crucial to examine the spatial and temporal variations of blue and green water (BW and GW) in future contexts. This research focuses on the Jialing River Basin, utilizing an enhanced Soil & Water Assessment Tool (SWAT) model alongside CMIP6 data, and selects representative years of dry-hot composite events through the Dry-Hot Magnitude Index (DHMI) to study the alterations in blue and green water across various future scenarios. The findings indicate that: (1) The enhanced CO2-SWAT model minimizes uncertainty in future projections and details alterations in blue and green water within these projections. (2) In the future, higher precipitation and temperature indicate a trend towards warmer and wetter conditions. Given these circumstances, the yearly fluctuations in blue and green water within the Jialing River Basin are anticipated to be more significant in the distant future than in the short future, with the majority of the basin’s blue and green water levels likely surpassing historical records. (3) Rising temperatures encourage plant growth, resulting in an earlier growing season; however, extremely high temperatures can hinder vegetation development, impacting the transformation and allocation of blue and green water within the basin. (4) In most areas of the basin, extreme heat and dryness lead to a notable shift from blue water to green water, linked to soil moisture buildup prior to drought conditions. Despite the suppression of vegetation activity due to elevated CO2 and high temperatures in future scenarios, increased vegetation growth demands in agricultural areas exacerbate soil water shortages and elevate future risks to water and food security. The findings provide scientific support for comprehensive water resource management of the Jialing River Basin and offer scientific references for water resource allocation and drought response under climate change in the basin.

Intelligent prosthetic hands typically require an increase in the number of acquisition channels to improve gesture recognition accuracy, resulting in increased device complexity and cost. However, there are individual differences in muscle strength, body mass index, and exercise habits. Electromyographic prosthetic hands currently use standardized electromyographic channel configurations, which lack adaptability to individual differences. To address these issues, this paper proposes the electrode configuration adaptive optimization algorithm, which enhances and integrates traditional genetic algorithms and simulated annealing algorithms, and implements adaptive optimization solutions for different subjects. Experimental results show that the optimization outcomes differ among different subjects. Compared to a single optimization algorithm, the proposed algorithm can adaptively optimize the electrode configuration based on individual differences while ensuring recognition effectiveness, retaining electrode channel information that significantly contributes to gesture classification recognition, and meeting the stable recognition of their motion intentions by different subjects.

A common assumption in side-channel analysis is that the attacker knows the cryptographic algorithm implementation of the victim. However, many labsetting studies implicitly extend this assumption to the knowledge of the source code, by inserting triggers to measure, locate or align the Cryptographic Operations (CO) in the trace. For real-world attacks, the source code is typically unavailable, which poses a challenge for locating the COs thus reducing the effectiveness of many methods. In contrast, obtaining the (partial) binary firmware is more prevalent in practical attacks on embedded devices. While binary code theoretically encapsulates necessary information for side-channel attacks on software-implemented cryptographic algorithms, there is no systematic study on leveraging this information to facilitate side-channel analysis. This paper introduces a novel and general framework that utilizes binary information for the automated locating of COs on side-channel traces. We first present a mechanism that maps the execution flow of binary instructions onto the corresponding side-channel trace through a tailored static binary instrumentation process, thereby transforming the challenge of locating COs into one of tracing cryptographic code execution within the binary. For the latter, we propose a method to retrieve binary instruction addresses that are equivalent to the segmenting boundaries of the COs within side-channel traces. By identifying the mapping points of these instructions on the trace, we can obtain accurate segmentation labeling for the sidechannel data. Further, by employing the well-labeled side-channel segments obtained on a profiling device, we can readily identify the locations of COs within traces collected from un-controllable target devices. We evaluate our approach on various devices and cryptographic software, including a real-world secure boot program. The results demonstrate the effectiveness of our method, which can automatically locate typical COs, such as AES or ECDSA, in raw traces using only the binary firmware and a profiling device. Comparison experiments indicate that our method outperforms existing techniques in handling noisy or jittery traces and scales better to complex COs. Performance evaluation confirms that the runtime and storage overheads of the proposed approach are practical for real-world deployment.

Transglutaminase (TGase) can catalyze the crosslinking within or between protein molecules, improving the structural and functional properties of proteins. It has been widely used in artificial meat, yogurt products, flour products and other foods. In this study, a high yield TGase strain was screened from fermented soybean, and it was identified as the Bacillus amyloliquefaciens XCT-09. Then, the transglutaminase (X9Tgl) from XCT-09 was expressed in Escherichia coli BL21(DE3), and the enzyme activity of purified X9Tgl reached 5.73 U/mg. Subsequently, the catalytic mechanism of X9Tgl was elucidated, and the X9Tgl contained the active center of E115, C116 and E187, as well as the substrate binding sites W149 and F69. Furthermore, this study characterized the enzymatic properties of X9Tgl, and the optimal catalytic temperature and pH were 60 °C and 6, respectively. Moreover, X9Tgl exhibited stronger thermal stability and pH tolerance than STG, and it was not inhibited by the majority of metal ions. This study successfully identified a X9Tgl with high thermal stability, and pH tolerance, which provided a potential TGase resource for application in the food and medicine fields.

Background: Preliminary evidence provides support for the proposition that there is a dissociative subtype of Complex posttraumatic stress disorder (CPTSD). Research on this proposition would extend our knowledge on the association between CPTSD and dissociation, guide contemporary thinking regarding placement of dissociation in the nosology of CPTSD, and inform clinically useful assessment and intervention.Objectives: The present study aimed to investigate the co-occurring patterns of CPTSD and dissociative symptoms in a large sample of trauma exposed adolescents from China, and specify clinical features covariates of such patterns including childhood trauma, comorbidities with major depressive disorder (MDD) and generalized anxiety disorder (GAD), and functional impairment.Methods: Participants included 57,984 high school students exposed to the coronavirus disease 2019 (COVID-19) pandemic. CPTSD and dissociative symptoms, childhood traumatic experience, and functional impairment were measured with the Global Psychotrauma Screen for Teenagers (GPS-T). Major depressive disorder (MDD) and generalized anxiety disorder (GAD) symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7), respectively. Latent class analysis (LCA) was employed to test the co-occurring patterns of CPTSD and dissociative symptoms. Analysis of covariance (ANCOVA) and chi-square tests were respectively used to examine between-class differences in continuous and categorical clinical covariates.Results: A 5-class model emerged as the best-fitting model, including resilience, predominantly PTSD symptoms, predominantly disturbances in self-organization (DSO)symptoms, predominantly CPTSD symptoms, and CPTSD dissociative subtype classes. The CPTSD dissociative subtype class showed the lowest level of functioning and the highest rates of MDD, GAD and childhood trauma.Conclusions: Our findings provide initial empirical evidence supporting the existence of a dissociative subtype of CPTSD, and inform for further research and clinical practice on traumatized individuals.

Abstract To investigate how cell elongation impacts extracellular electron transfer (EET) of electroactive microorganisms (EAMs), the division of model EAM Shewanella oneidensis (S. oneidensis) MR‐1 is engineered by reducing the formation of cell divisome. Specially, by blocking the translation of division proteins via anti‐sense RNAs or expressing division inhibitors, the cellular length and output power density are all increased. Electrophysiological and transcriptomic results synergistically reveal that the programmed cell elongation reinforces EET by enhancing NADH oxidation, inner‐membrane quinone pool, and abundance of c‐type cytochromes. Moreover, cell elongation enhances hydrophobicity due to decreased cell‐surface polysaccharide, thus facilitates the initial surface adhesion stage during biofilm formation. The output current and power density all increase in positive correction with cellular length. However, inhibition of cell division reduces cell growth, which is then restored by quorum sensing‐based dynamic regulation of cell growth and elongation phases. The QS‐regulated elongated strain thus enables a cell length of 143.6 ± 40.3 µm (72.6‐fold of that of S. oneidensis MR‐1), which results in an output power density of 248.0 ± 10.6 mW m−2 (3.41‐fold of that of S. oneidensis MR‐1) and exhibits superior potential for pollutant treatment. Engineering cellular length paves an innovate avenue for enhancing the EET of EAMs.

Purpose: This study represents a prospective phase I clinical research to verify the effectiveness and reliability of hydrogel application in Chinese cervical cancer patients. Materials and Methods: Eight patients were enrolled in the study. After completing intensity-modulated radiotherapy at 50.4 Gy/28 fractions, a 10 mL injection of hydrogel was administered to each patient through the posterior vaginal fornix under CT-guidance. Image-guided brachytherapy under CT or MRI guidance was given with a target dose of 6 Gy in 5 fractions to the high-risk clinical target volume. Rectal, sigmoid colon, and bladder D2cm3 were recorded for each brachytherapy. MRI scans were performed to measure the distance between the rectum and the cervix or tumor, as well as the spacer gel volume. Patients’ QLQ-C30 and QLQ-CX24 scores were recorded to assess treatment outcomes, and all adverse events were documented. Results: Among the eight patients, the average D2cc was 60.9 ± 3.4 Gy for the rectum, 64.7 ± 6.8 Gy for sigmoid colon and 77.1 ± 7.4 Gy for bladder, respectively. The distance between the cervix and rectum significantly increased after gel injection. None of the eight patients experienced grade 3 or higher acute toxic reactions during brachytherapy. None patient experienced late rectal toxicity. No adverse events definitively associated with the hydrogel were observed. Patients’ subjective quality of life scores did not significantly change before and after gel injection. The reduction ro the volume of the hydrogel were observed during the 24 to 36 weeks after injection. Conclusion: The application of the hydrogel effectively increased the distance between the cervix and rectum in brachytherapy for cervical cancer, limiting the rectal dose without increasing doses to other critical organs. In the short term, no severe adverse events were observed, indicating the safety and reliability of this approach. Further research is warranted to confirm its long-term safety and effectiveness.

Sweetness is an important driver for food intake and one of the most popular taste sensations. At present, there is a preliminary understanding of the signaling pathways of sweetness and the mechanisms that affect sweetness sensation. Human sweetness sensation is expressed through at least two types of signaling pathways, one of which is mediated by heterodimers formed by the taste receptor family 1 member 2 (T1R2) and the taste receptor family 1 member 3 (T1R3), whereas the other by sodium glucose co-transporters (SGLT) and glucose transporters (GLUT). This article reviews the structure of T1R2/T1R3 heterodimer and the mechanism of sweet signal transduction, and discusses the effects of internal and external factors such as bitterness, sourness, umami, anti-sweetness substances, aroma compounds, saliva, obesity and age on sweetness sensation. The shortcomings of the current research are presented, such as little effect of the current available noncaloric sweeteners (NCSs) in attenuating obesity and diabetes, few studies on the interactions of sweet taste with the other four taste sensations, unclear understanding of the molecular basis of the regulation mechanisms of anti-sweetness substances at the receptor level, and limitations of using rodents as an experimental substitute for humans in sweet taste research. This article aims to understand how sweet substances exert their functions in complex food matrices, hoping to provide theoretical support and ideas for future development and application of NCS-containing foods.

In order to meet the power source requirements of C-band linear accelerators for industrial applications, a C-band high power klystron operating at a frequency of 5 712 MHz was developed. For this klystron, the development objective of the output power is no less than 3.5 MW and the efficiency is no less than 35%. During the entire design process, the output power was optimized to over 4 MW and the power efficiency over 40% to compensate for the disadvantage effects caused by manufacturing and testing errors in the development processes. Firstly, the electron optics system with a Pierce gun and a combination of five forward and one reverse focusing coils was designed. The Pierce gun with a perveance of 2 μP was adopted and the beam voltage and current were chosen as 120 kV and 83.3 A. By iteratively calculating the structure of the electron gun with EGUN code and optimizing the magnetic field between the electron gun and the beam-wave interaction section, the final electron beam pass rate reaches 100% and the fluctuation of the beam envelop is only 4.8%. Secondly, the efficiency optimization and PIC simulation of the beam-wave interaction section were carried out using the one dimensional AJDISK code, 1.5 dimensional KlyC code and three dimensional CST code. The scheme of six resonant cavities was ultimately determined and the basic cavity parameters were optimized based on the principles of stagger tuning. The simulation results of different codes all indicate that the efficiency can reach above 46.5%, and the output power can all reach above 4.650 MW. And the influence of frequency errors and output external quality factor on efficiency was also analyzed to guide the manufacturing process. After that, the mechanical structure of cavities was designed and all cavities were manufactured with oxygen free copper. The cold test and tuning of all cavities were carried out and the frequency error is mostly within the range of ±5 MHz, which basically does not affect the output power. Finally, the electron gun, the beam-wave interaction section and the collector were welded together. And the high power test was conducted immediately after the first high power C-band klystron protype was completed. When the electron gun operates at the voltage of 115 kV and current of 79.6 A, the klystron peak output power reaches 3.52 MW, the gain reaches 45.5 dB and the efficiency reaches about 38.5%. The high power test results show that this C-band high power klystron achieves the expected development goals.

Abstract Background Temporomandibular joint osteoarthritis (TMJOA) has a high incidence rate, but its pathogenesis remains unclear. Circadian rhythm is an important oscillation in the human body and influences various biological activities. However, it is still unclear whether circadian rhythm affects the onset and development of TMJOA. Methods We disrupted the normal rhythm of rats and examined the expression of core clock genes in the mandibular condylar cartilage of the jaw and histological changes in condyles. After isolating rat mandibular condylar chondrocytes, we upregulated or downregulated the clock gene Per1, examined the expression of cartilage matrix-degrading enzymes, tested the activation of the GSK3β/β-CATENIN pathway and verified it using agonists and inhibitors. Finally, after downregulating the expression of Per1 in the mandibular condylar cartilage of rats with jet lag, we examined the expression of cartilage matrix-degrading enzymes and histological changes in condyles. Results Jet lag led to TMJOA-like lesions in the rat mandibular condyles, and the expression of the clock gene Per1 and cartilage matrix-degrading enzymes increased in the condylar cartilage of rats. When Per1 was downregulated or upregulated in mandibular condylar chondrocytes, the GSK3β/β-CATENIN pathway was inhibited or activated, and the expression of cartilage matrix-degrading enzymes decreased or increased, which can be rescued by activator and inhibitor of the GSK3β/β-CATENIN pathway. Moreover, after down-regulation of Per1 in mandibular condylar cartilage in vivo, significant alleviation of cartilage degradation, cartilage loss, subchondral bone loss induced by jet lag, and inhibition of the GSK3β/β-CATENIN signaling pathway were observed. Circadian rhythm disruption can lead to TMJOA. The clock gene Per1 can promote the occurrence of TMJOA by activating the GSK3β/β-CATENIN pathway and promoting the expression of cartilage matrix-degrading enzymes. The clock gene Per1 is a target for the prevention and treatment of TMJOA.

Abstract Background Reducing production costs while producing high-quality livestock and poultry products is an ongoing concern in the livestock industry. The addition of oil to livestock and poultry diets can enhance feed palatability and improve growth performance. Emulsifiers can be used as potential feed supplements to improve dietary energy utilization and maintain the efficient productivity of broilers. Therefore, further investigation is warranted to evaluate whether dietary emulsifier supplementation can improve the efficiency of fat utilization in the diet of yellow-feathered broilers. In the present study, the effects of adding emulsifier to the diet on lipid metabolism and the performance of yellow-feathered broilers were tested. A total of 240 yellow-feasted broilers (21-day-old) were randomly divided into 4 groups (6 replicates per group, 10 broilers per replicate, half male and half female within each replicate). The groups were as follows: the control group (fed with basal diet), the group fed with basal diet supplemented with 500 mg/kg emulsifier, the group fed with a reduced oil diet (reduced by 1%) supplemented with 500 mg/kg emulsifier, and the group fed with a reduced oil diet supplemented with 500 mg/kg emulsifier. The trial lasted for 42 days, during which the average daily feed intake, average daily gain, and feed-to-gain ratio were measured. Additionally, the expression levels of lipid metabolism-related genes in the liver, abdominal fat and each intestinal segment were assessed. Results The results showed that compared with the basal diet group, (1) The average daily gain of the basal diet + 500 mg/kg emulsifier group significantly increased (P

Abstract Introduction Lung cancer (LC) is the most common solid tumor and is currently considered the primary cause of cancer-related deaths worldwide. In clinical efficacy studies, it was not difficult to find that the combination of SFI and chemotherapy could improve the general condition of patients, reduce the side effects of chemotherapy drugs, and have a cooperative antitumor effect in NSCLC patients. However, whether SFI can be used as a novel antitumor drug is still unknown. Methods First, meta-analysis aimed to explore the efficacy of SFI in NSCLC patients, and SFI was identified by ultra-performance liquid chromatography‒mass spectrometry (UPLC‒MS). Cell proliferation, migration, and invasion were explored by Cell Counting Kit-8 (CCK-8), scratch healing, and Transwell assays, respectively. Cell cycle and apoptosis assays were performed by flow cytometry. Transcriptome sequencing analysis was performed in four NSCLC cell lines. Differential expression analysis was used to identify potential targets. Apoptosis-related protein levels were detected by Western blotting assays. The effects of SFI in NSCLC were further investigated by mouse xenografts. Results SFI could markedly improve the chemotherapy efficacy of NSCLC patients. The main active ingredients include flavonoids and terpenoids, which can effectively exert antitumor effects. SFI could not only inhibit tumor cell proliferation and cell migration/invasion but also regulate the cell cycle and promote tumor cell apoptosis. In NSCLC, SFI could enhance the transcription level of the CHOP gene, thereby upregulating the expression of the proapoptotic proteins Bax and caspase 3, and inhibiting the expression of the antiapoptotic protein Bcl-2. SFI hindered the growth of mouse NSCLC xenografts in vivo. Conclusions SFI hindered tumor progression and might promote apoptosis by increasing the expression of Bax, caspase 3 and decreasing the level of Bcl-2 in NSCLC.

Abstract Conducting polymer hydrogel can address the challenges of stricken biocompatibility and durability. Nevertheless, conventional conducting polymer hydrogels are often brittle and weak due to the intrinsic quality of the material, which exhibits viscoelasticity. This property may cause a delay in sensor response time due to hysteresis. To overcome these limitations, we have designed a wrinkle morphology three‐dimensional (3D) substrate using digital light processing technology and then followed by in situ polymerization to form interpenetrating polymer network hydrogels. This novel design results in a wrinkle morphology conducting polymer hydrogel elastomer with high precision and geometric freedom, as the size of the wrinkles can be controlled by adjusting the treating time. The wrinkle morphology on the conducting polymer hydrogel effectively reduces its viscoelasticity, leading to samples with quick response time, low hysteresis, stable cyclic performance, and remarkable resistance change. Simultaneously, the 3D gradient structure augmented the sensor's sensitivity under minimal stress while exhibiting consistent sensing performance. These properties indicate the potential of the conducting polymer hydrogel as a flexible sensor.

BackgroundObservational studies have shown an increased risk of ocular inflammatory diseases in patients with ankylosing spondylitis (AS), but the genetically predicted association remains unclear. The aim of this study was to systematically assess the causal relationship between AS and ocular inflammatory diseases.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between AS and several common ocular inflammatory diseases based on genome-wide association study (GWAS) data and public health data. Five methods, namely, inverse-variance weighted (IVW), MR–Egger, weighted median, weighted mode, and simple mode, were used. Sensitivity analysis was performed using MR–Egger intercept, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Cochran’s Q test, outlier methods, leave-one-out analysis, and funnel plots.ResultsThe MR analysis showed a significantly increased risk of uveitis (ORIVW = 2.825, 95%CIIVW = 1.709–4.672, and PIVW < 0.001), iridocyclitis (ORIVW = 3.806, 95%CIIVW = 2.809–5.157, and PIVW < 0.001), scleritis (ORIVW = 1.738, 95%CIIVW = 1.190–2.539, and PIVW < 0.001), and episcleritis (ORIVW = 5.113, 95%CIIVW = 2.067–12.645, and PIVW = 0.004) associated with AS. However, no correlation was found between genetically predicted AS and keratitis (ORIVW = 1.041, 95%CIIVW = 0.886–1.222, and PIVW = 0.628) and optic neuritis (ORIVW = 0.868, 95%CIIVW = 0.441–1.709, and PIVW = 0.682).ConclusionAS increases the genetically predicted risk for uveitis, iridocyclitis, scleritis, and episcleritis. No potential association of AS with keratitis and optic neuritis was found. It may provide clues for the prevention of AS complications.

Abstract This paper introduces the subarray partition based on the sparse array weighted K‐means clustering method, which extends the conventional K‐means clustering method through the inclusion of a weight matrix approach. This matrix is derived by recording the frequency of each element's occurrence across multiple independent sparse arrays, thereby generating a frequency matrix. The performance of SWKCM is demonstrated through simulations and comparisons with four similar methods. To assess the effectiveness and superiority of the SWKCM, it is applied to the subarray partition of a 40×40 uniform planar phased array and compared with the other four methods. The simulation results show that the proposed SWKCM method maintains comparable sidelobe suppression capabilities to those of KCM, achieving a normalized peak sidelobe level of ‐43.1076 dB. Furthermore, compared to the K‐means clustering method, the sparse array weighted K‐means clustering method significantly enhances the stability of subarray partition outcomes, as evidenced by a reduction in the peak sidelobe level standard deviation from 1.0991 to 0.8104, resulting in a 26.3% decrease in variability.

Summary: The study of pattern formation has benefited from our ability to reverse-engineer gene regulatory network (GRN) structure from spatiotemporal quantitative gene expression data. Traditional approaches have focused on systems where the timescales of pattern formation and morphogenesis can be separated. Unfortunately, this is not the case in most animal patterning systems, where pattern formation and morphogenesis are co-occurring and tightly linked. To elucidate patterning mechanisms in such systems we need to adapt our GRN inference methodologies to include cell movements. In this work, we fill this gap by integrating quantitative data from live and fixed embryos to approximate gene expression trajectories (AGETs) in single cells and use these to reverse-engineer GRNs. This framework generates candidate GRNs that recapitulate pattern at the tissue level, gene expression dynamics at the single cell level, recover known genetic interactions and recapitulate experimental perturbations while incorporating cell movements explicitly for the first time.

Short-chain fatty acids (SCFAs), a subset of organic fatty acids with carbon chains ranging from one to six atoms in length, encompass acetate, propionate, and butyrate. These compounds are the endproducts of dietary fiber fermentation, primarily catalyzed by the glycolysis and pentose phosphate pathways within the gut microbiota. SCFAs act as pivotal energy substrates and signaling molecules in the realm of animal nutrition, exerting a profound influence on the intestinal, immune system, and intestinal barrier functions. Specifically, they contibute to 60-70% of the total energy requirements in ruminants and 10-25% in monogastric animals. SCFAs have demonstrated the capability to effectively modulate intestinal pH, optimize the absorption of mineral elements, and impede pathogen invasion. Moreover, they enhance the expression of proteins associated with intestinal tight junctions and stimulate mucus production, thereby refining intestinal tissue morphology and preserving the integrity of the intestinal structure. Notably, SCFAs also exert anti-inflammatory properties, mitigating inflammation within the intestinal epithelium and strengthening the intestinal barrier’s defensive capabilities. The present review endeavors to synthesize recent findings regarding the role of SCFAs as crucial signaling intermediaries between the metabolic activities of gut microbiota and the status of porcine cells. It also provides a comprehensive overview of the current literature on SCFAs’ impact on immune responses within the porcine intestinal mucosa.