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Abstract Intervention efforts against falciparum malaria in high-transmission regions remain challenging, with rapid resurgence typically following their relaxation. Such resilience co-occurs with incomplete immunity and a large transmission reservoir from high asymptomatic prevalence. Incomplete immunity relates to the large antigenic variation of the parasite, with the major surface antigen of the blood stage of infection encoded by the multigene and recombinant family known as var. With a stochastic agent-based model, we investigate the existence of a sharp transition in resurgence ability with intervention intensity and identify molecular indicators informative of its proximity. Their application to survey data with deep sampling of var sequences from individual isolates in northern Ghana suggests that the transmission system was brought close to transition by intervention with indoor residual spraying. These results indicate that sustaining and intensifying intervention would have pushed malaria dynamics to a slow-rebound regime with an increased probability of local parasite extinction.

Marinesco-Sjögren syndrome(MSS) is a rare autosomal recessive inherited disease characterized by cerebellar ataxia, early-onset cataracts, chronic myopathy, and intellectual disability and developmental delay at varied degrees. Some patients may manifest such symptoms as short stature, hypergonadotropic hypogonadism, various skeletal abnormalities resulted from the muscular weakness, and others. This article reports the clinical and molecular diagnosis process of two MSS cases with global developmental delay. We found the compound heterozygous variants c.109delG(p.Glu37Serfs*4)and c.353G > C (p.Arg118Thr), c.443delA(p.Lys148Argfs*10)and c.707A > G (p.Asn236Ser) by Trio-whole exome sequencing(Trio-WES)which are evaluated as pathogenic, and uncertain significant, pathogenic and likely pathogenic variants separately.We provided genetic consultation based on the molecular diagnosis and evaluated the risk for the offsprings in the families. By introducing the two cases and literature review, this article aims at improving the understanding of MSS and providing reference to the diagnosis of the disease.

Abstract LHPP has been shown to be a new tumor suppressor, and has a tendency to be under-expressed in a variety of cancers. Oncolytic virotheray is a promising therapeutics for lung cancer in recent decade years. Here we successfully constructed a new recombinant oncolytic adenovirus GD55-LHPP and investigated the effect of GD55-LHPP on the growth of lung cancer cells in vitro and in vivo. The results showed that LHPP had lower expression in either lung cancer cells or clinical lung cancer tissues compared with normal cells or tissues, and GD55-LHPP effectively mediated LHPP expression in lung cancer cells. GD55-LHPP could effectively inhibit the proliferation of lung cancer cell lines and rarely affected normal cell growth. Mechanically, the oncolytic adenovirus GD55-LHPP was able to induce stronger apoptosis of lung cancer cells compared with GD55 through the activation of caspase signal pathway. Notably, GD55-LHPP also activated autophagy-related signal pathway. Further, GD55-LHPP efficiently inhibited tumor growth in lung cancer xenograft in mice and prolonged animal survival rate compared with the control GD55 or PBS. In conclusion, the novel construct GD55-LHPP provides a valuable strategy for lung cancer-targeted therapy and develop the role of tumor suppress gene LHPP in lung cancer gene therapy.

Flame kernel generation is essential to the stability and efficiency of combustion in a spark engine. In this study, the initial process of flame kernel generation was studied in an optical spark engine. The engine was operated with the λ adjusted from 1.0 to 1.5, respectively. Meanwhile, the continuous arc motion was inventively quantified. First, the impact of single-coil and multi-coil discharge on the stability of the combustion and knocking tendency are examined. Secondly, the differences in arc development between single-coil and multi-coil discharge and the effect of the shortening phenomenon on the generation of the flame kernels are compared by optical images. Finally, arc shortening feathers (including timing, extent, and spatial location) are statistically analyzed over multiple cycles in conjunction with combustion phase. The results show that multi-coil discharge can make the flame kernels larger, which could keep the flame kernels from quenching. They also show that variations in arc shortening are linked to cycle-to-cycle fluctuations. Furthermore, a principal component analysis is done on the features of the first two arc shortenings and the CA05 phases. Precision control of the arc shortening features can greatly enhance the spark engine’s initial flame kernel stability and lower cycle-to-cycle fluctuations.

Abstract Toll‐like receptors (TLRs) are inflammatory triggers and belong to a family of pattern recognition receptors (PRRs) that are central to the regulation of host protective adaptive immune responses. Activation of TLRs in innate immune myeloid cells directs lymphocytes to produce the most appropriate effector responses to eliminate infection and maintain homeostasis of the body's internal environment. Inappropriate TLR stimulation can lead to the development of general autoimmune diseases as well as chronic and acute inflammation, and even cancer. Therefore, TLRs are expected to be targets for therapeutic treatment of inflammation‐related diseases, autoimmune diseases, microbial infections, and human cancers. This review summarizes the recent discoveries in the molecular and structural biology of TLRs. The role of different TLR signaling pathways in inflammatory diseases, autoimmune diseases such as diabetes, cardiovascular diseases, respiratory diseases, digestive diseases, and even cancers (oral, gastric, breast, colorectal) is highlighted and summarizes new drugs and related clinical treatments in clinical trials, providing an overview of the potential and prospects of TLRs for the treatment of TLR‐related diseases.

Abstract Background Metabolism reprogramming plays a vital role in glioblastoma (GBM) progression and recurrence by producing enough energy for highly proliferating tumor cells. In addition, metabolic reprogramming is crucial for tumor growth and immune‐escape mechanisms. Epidermal growth factor receptor (EGFR) amplification and EGFR‐vIII mutation are often detected in GBM cells, contributing to the malignant behavior. This study aimed to investigate the functional role of the EGFR pathway on fatty acid metabolism remodeling and energy generation. Methods Clinical GBM specimens were selected for single‐cell RNA sequencing and untargeted metabolomics analysis. A metabolism‐associated RTK‐fatty acid‐gene signature was constructed and verified. MK‐2206 and MK‐803 were utilized to block the RTK pathway and mevalonate pathway induced abnormal metabolism. Energy metabolism in GBM with activated EGFR pathway was monitored. The antitumor effect of Osimertinib and Atorvastatin assisted by temozolomide (TMZ) was analyzed by an intracranial tumor model in vivo. Results GBM with high EGFR expression had characteristics of lipid remodeling and maintaining high cholesterol levels, supported by the single‐cell RNA sequencing and metabolomics of clinical GBM samples. Inhibition of the EGFR/AKT and mevalonate pathways could remodel energy metabolism by repressing the tricarboxylic acid cycle and modulating ATP production. Mechanistically, the EGFR/AKT pathway upregulated the expressions of acyl‐CoA synthetase short‐chain family member 3 (ACSS3), acyl‐CoA synthetase long‐chain family member 3 (ACSL3), and long‐chain fatty acid elongation‐related gene ELOVL fatty acid elongase 2 (ELOVL2) in an NF‐κB‐dependent manner. Moreover, inhibition of the mevalonate pathway reduced the EGFR level on the cell membranes, thereby affecting the signal transduction of the EGFR/AKT pathway. Therefore, targeting the EGFR/AKT and mevalonate pathways enhanced the antitumor effect of TMZ in GBM cells and animal models. Conclusions Our findings not only uncovered the mechanism of metabolic reprogramming in EGFR‐activated GBM but also provided a combinatorial therapeutic strategy for clinical GBM management.

Rotor-type cross-media vehicles always induce considerably complex mixed air–water flows when approaching the water surface, resulting in relative thrust loss and structural damage on rotor. The interactions between a water surface and rotor wake bring potential risks to the cross-media process, which is known as the near-water effect of the rotor. In this paper, experimental investigations are used to explore the fluid dynamics of the near-water effect of the rotor. Qualitative droplet observation was carried out on the 0.25 m and 0.56 m diameter commercial rotor blades and the 0.07 m diameter ducted fan near the water surface first to gain a qualitative understanding of droplet characteristics. The results show that the rotor wake caused water surface deformation, droplet tearing off, splashing, and entrainment into the rotor disk. The depression formed by the rotor downwash flow impacting the water surface is named as three modes: dimpling, splashing, and penetrating, and the correlation between the depression modes and the aerodynamic characteristics of the rotor is primary analyzed. The flow mechanisms of dimpling mode were studied using the particle image velocimetry (PIV) technique. The results showed that the cavity and liquid crown obviously alter the flow direction of water surface jets, but not all rotors near water enter the vortex ring state. Two splashing mechanisms were revealed, including the direct ejection of droplets at the rim of depression and the tearing of liquid crown by the water surface jets. The blade tip vortex in the surface jet is a potential cause of entrainment into the rotor disk and secondary breakup of the droplet.

A large number of distributed photovoltaics are linked to the distribution network, which may cause serious power quality problems. Based on edge computing, this article put forward a strategy that aggregates multiple distributed resources, such as distributed photovoltaics, energy storage, and controllable load to solve this problem, emphasizing the coordination and optimization between distributed resources. Firstly, an edge computing architecture that can be fully applicable to the coordination of source–storage–loads is constructed. Based on this architecture, the distributed photovoltaic, energy storage and interruptible loads are optimized with the minimum operating cost of edge computation nodes as the objective function. Combined with the operation requirements of the distribution system, lessen the system network loss and make sure the stable and safe operation of the net; Finally, the model is changed with a second-order cone model and verified in an improved IEEE 33 node example. The results show that this method can effectively reduce the loss cost of the system, and can effectively solve the problem of system voltage exceeding the limit, reduce the voltage fluctuation, and maintain the safe and stable operation of the system.

Abstract Background Stroke represents the second most prevalent contributor to global mortality. The Chinese Visceral Adiposity Index (CVAI) serves as an established metric for assessing visceral adiposity in the Chinese population, exhibiting prognostic capabilities. This investigation aimed to explore the association of CVAI and new-onset stroke among middle-aged and older Chinese populations. Methods The study employed data from the 2011 and 2018 China Health and Retirement Longitudinal Study (CHARLS) to assess the association of CVAI and the incidence of new-onset stroke. Utilizing a directed acyclic graph (DAG), 10 potential confounders were identified. Moreover, to explore the association between CVAI and new-onset stroke, three multifactor logistic regression models were constructed, accounting for the identified confounders and mitigating their influence on the findings. Results The study comprised 7070 participants, among whom 417 (5.9%) experienced new-onset strokes. After controlling for confounding variables, regression analysis suggested that the new-onset stroke’s highest risk was linked to the fourth quartile (Q4) of the CVAI, with an odds ratio (OR) of 2.33 and a 95% confidence interval (CI) of 1.67–3.28. The decision tree analysis demonstrated a heightened probability of new-onset stroke among hypertensive individuals with a CVAI equal to or greater than 83, coupled with a C-reactive protein level no less than 1.1 mg/l. Age seemed to have a moderating influence on the CVAI and new-onset stroke association, exhibiting a more prominent interaction effect in participants under 60 years. Conclusions In middle-aged and older Chinese populations, a linear relationship was discerned between CVAI and the probability of new-onset stroke. CVAI provides a predictive framework for stroke incidence in this demographic, laying the groundwork for more sophisticated risk prediction models that improve the precision and specificity of stroke risk evaluations.

In this paper, we first propose a Markov chain-based automatic composition method to construct a song set using classical and traditional music as a sample. Using probability matrices, experiments are conducted to generate pitch and time value sequences, and melodic segments of traditional music are generated using transformation techniques. Secondly, a traditional music digital resource library that integrates multiple functions is constructed by utilizing various information technologies. Finally, based on the existing classification dimensions, the relationship between various types of influencing factors in the inheritance of traditional music was analyzed, and the structure of the questionnaire was initially constructed. The results show that the correlation coefficients between the cultural inheritance of traditional music and its resources, environmental threats, development level, diversified values, public demand, and social cognition are 0.4235, 0.0953, 0.3594, 0.4253, 0.5348, and 0.5224, respectively, and there is a significant positive influence. This paper provides some theoretical and practical guidance for the protection and inheritance of traditional music.

Type I R-M systems help establish the prokaryotic DNA methylation landscape and provide protection against invasive DNA. Here, the authors report on detailed structural and molecular mechanisms of a non-canonical type I R-M methyltransferase.

Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated regenerative potential for cell-free bone tissue engineering, nevertheless, certain challenges, including the confined therapeutic potency of exosomes and ineffective delivery method, are still persisted. Here, we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth (SHEDs) via comprehensive proteomics analysis, and the corresponding hypoxic exosomes (H-Exo) exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion, VEGF signaling pathway, and thyroid hormone synthesis. Then, we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection. This platform is based on a simple adsorbing technique, where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide) (PLGA) microspheres with bioinspired polydopamine (PDA) coating (PMS-PDA microspheres). The PMS-PDA microspheres could effectively adsorb exosomes, show sustained release of H-Exo for 21 days with high bioactivity, and induce vascularized bone regeneration in 5-mm rat calvarial defect. These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration, hence facilitating the clinical translation of exosome-based therapy.

In recent decades, the traditional treatment of head and neck neoplasms has reached a bottleneck with limited improvement in overall survival. Nevertheless, the emerging field of immunotherapy has shown promise. Literature on research into immunotherapy for head and neck neoplasms was retrieved from WoSCC. Citespace was used as a scientometric analysis tool for text mining and visualization of the scientific literature. This analysis included 1915 documents. Recently, the annual number of publications and citations has been growing rapidly. ‘Oncology’ was the most popular research area. The most dominant institution and country were the University of Pittsburgh and the USA. Ferris RL was not only the most prolific but also the most cited author, demonstrating a strong influence and reputation. Of the ten core journals identified in this field, Cancer Research ranked first. ‘Regulatory T cell’, ‘PD-1’ and ‘biomarker’ were regarded as current hotspots, while ‘recurrent’ and ‘nivolumab’ were considered as trending keywords. The most cited reference was Ferris RL (2016). Notably, the front trends and future directions in the field may lie in the clinical practice of combination therapy of immunotherapy plus other therapies, the mechanism of impaired immune surveillance, and the improvement in resistance to immunotherapeutic agents. It is firmly believed that the present scientometric analysis has provided both a macroscopic and microscopic overview of research into immunotherapy for head and neck neoplasms, which will assist researchers and oncologists to better understand this discipline and thus promote further development and policies in this field.

Metal phosphides with multi-element components and amorphous structure represent a novel kind of electrocatalysts for promising activity and durability towards the oxygen evolution reaction (OER). In this work, a two-step strategy, including alloying and phosphating processes, is reported to synthesize trimetallic amorphous PdCuNiP phosphide nanoparticles for efficient OER under alkaline conditions. The synergistic effect between Pd, Cu, Ni, and P elements, as well as the amorphous structure of the obtained PdCuNiP phosphide nanoparticles, would boost the intrinsic catalytic activity of Pd nanoparticles towards a wide range of reactions. These obtained trimetallic amorphous PdCuNiP phosphide nanoparticles exhibit long-term stability, nearly a 20-fold increase in mass activity toward OER compared with the initial Pd nanoparticles, and 223 mV lower in overpotential at 10 mA cm−2. This work not only provides a reliable synthetic strategy for multi-metallic phosphide nanoparticles, but also expands the potential applications of this promising class of multi-metallic amorphous phosphides.

At a time when effective tools for monitoring malaria control and eradication efforts are crucial, the increasing availability of molecular data motivates their application to epidemiology. The multiplicity of infection (MOI), defined as the number of genetically distinct parasite strains co-infecting a host, is one key epidemiological parameter for evaluating malaria interventions. Estimating MOI remains a challenge for high-transmission settings where individuals typically carry multiple co-occurring infections. Several quantitative approaches have been developed to estimate MOI, including two cost-effective ones relying on molecular data: i) THE REAL McCOIL method is based on putatively neutral single nucleotide polymorphism loci, and ii) the varcoding method is a fingerprinting approach that relies on the diversity and limited repertoire overlap of the var multigene family encoding the major Plasmodium falciparum blood-stage antigen PfEMP1 and is therefore under selection. In this study, we assess the robustness of the MOI estimates generated with these two approaches by simulating P. falciparum malaria dynamics under three transmission conditions using an extension of a previously developed stochastic agent-based model. We demonstrate that these approaches are complementary and best considered across distinct transmission intensities. While varcoding can underestimate MOI, it allows robust estimation, especially under high transmission where repertoire overlap is extremely limited from frequency-dependent selection. In contrast, THE REAL McCOIL often considerably overestimates MOI, but still provides reasonable estimates for low and moderate transmission. Regardless of transmission intensity, results for THE REAL McCOIL indicate that an inaccurate tail at high MOI values is generated, and that at high transmission, an apparently reasonable estimated MOI distribution can arise from some degree of compensation between overestimation and underestimation. As many countries pursue malaria elimination targets, defining the most suitable approach to estimate MOI based on sample size and local transmission intensity is highly recommended for monitoring the impact of intervention programs.

The glioma tumor microenvironment plays a crucial role in the development, occurrence, and treatment of gliomas. Glioma-associated macrophages (GAMs) are the most widely infiltrated immune cells in the tumor microenvironment (TME) and one of the major cell populations that exert immune functions. GAMs typically originate from two cell types-brain-resident microglia (BRM) and bone marrow-derived monocytes (BMDM), depending on a variety of cytokines for recruitment and activation. GAMs mainly contain two functionally and morphologically distinct activation types- classically activated M1 macrophages (antitumor/immunostimulatory) and alternatively activated M2 macrophages (protumor/immunosuppressive). GAMs have been shown to affect multiple biological functions of gliomas, including promoting tumor growth and invasion, angiogenesis, energy metabolism, and treatment resistance. Both M1 and M2 macrophages are highly plastic and can polarize or interconvert under various malignant conditions. As the relationship between GAMs and gliomas has become more apparent, GAMs have long been one of the promising targets for glioma therapy, and many studies have demonstrated the therapeutic potential of this target. Here, we review the origin and activation of GAMs in gliomas, how they regulate tumor development and response to therapies, and current glioma therapeutic strategies targeting GAMs.

BackgroundC-arm-guided percutaneous puncture balloon compression alone has risk factors of puncture failure, complications, and poor prognosis. Robot-assisted PBC can effectively increase the one-time puncture success rate and improve the safety of the procedure. However, evidence on the superiority of robot-assisted PBC over C-arm-guided PBC alone remains relatively limited.MethodsRetrospective analysis The clinical data of 60 patients with trigeminal neuralgia aged 60 years or older in the Department of Neurosurgery of the Fourth Hospital of Harbin Medical University from January 2021 to October 2021. There were 29 males and 31 females, and the patients’ ages ranged from 60 to 79 years, with an average of 71.63 ± 5.12 years. Two groups were divided according to the surgical method, the C-arm guidance-only group (30 cases, n = 30) and the robot-assisted group (30 cases, n = 30). The success rate of first puncture, total operation time, number of “pear-shaped” balloons, number of C-arm x-ray scans, and immediate postoperative relief rate were recorded in both groups, and follow-up was performed to evaluate the postoperative results and complications. The overall evaluation of postoperative results and complications was performed.ResultsIntraoperative balloon compression was successfully completed in all 60 patients, and the first puncture success rate was higher in the robot-assisted group than in the simple C-arm group, with a significant difference between the two groups (P 0.05). By the final follow-up, the mean VAS score of the robot-assisted group was lower than that of the simple C-arm group, and both were statistically significant (P

In this study, we examined the impact of principals' leadership style on the performance of teachers at the college level. For this purpose, we collect data from 300 college teachers via a random sampling approach. A self-administrated questionnaire (five-point Likert Scale) was used to collect data. For detecting relationships and differences among the opinions of the study's participants, correlation and the t-test were used. This study has revealed that the majority of college principals practice a democratic style of leadership at a higher level, Laissez-faire at a moderate level, and autocratic at a low level in their colleges. Moreover, it has been also revealed that when principals increase the use of a democratic leadership style, teacher performance may progress as well. The findings revealed that principals' leadership style had a positive impact on the performance of teachers. The study exposed a strong statistically positive relationship between college principals' leadership style and teacher performance. Thus, the results of this study suggest that college principals' should adopt the leadership style according to the level of teachers. The leadership style should be changed with specific situations in the colleges.

Gene therapy has revolutionized the field of medicine, offering new hope for those with common and rare diseases. For nearly three decades, adeno-associated virus (AAV) has shown significant therapeutic benefits in multiple clinical trials, mainly due to its unique replication defects and non-pathogenicity in humans. In the field of cardiovascular disease (CVD), compared with non-viral vectors, lentiviruses, poxviruses, and adenovirus vectors, AAV possesses several advantages, including high security, low immunogenicity, sustainable and stable exogenous gene expression etc., which makes AAV one of the most promising candidates for the treatment of many genetic disorders and hereditary diseases. In this review, we evaluate the current information on the immune responses, transport pathways, and mechanisms of action associated with AAV-based CVD gene therapies and further explore potential optimization strategies to improve the efficiency of AAV transduction for the improved safety and efficiency of CVD treatment. In conclusion, AAV-mediated gene therapy has great potential for development in the cardiovascular system.

Abstract Nowadays, orthodontic treatment has become increasingly popular. However, the biological mechanisms of orthodontic tooth movement (OTM) have not been fully elucidated. We were aiming to summarize the evidences regarding the mechanisms of OTM. Firstly, we introduced the research models as a basis for further discussion of mechanisms. Secondly, we proposed a new hypothesis regarding the primary roles of periodontal ligament cells (PDLCs) and osteocytes involved in OTM mechanisms and summarized the biomechanical and biological responses of the periodontium in OTM through four steps, basically in OTM temporal sequences, as follows: (1) Extracellular mechanobiology of periodontium: biological, mechanical, and material changes of acellular components in periodontium under orthodontic forces were introduced. (2) Cell strain: the sensing, transduction, and regulation of mechanical stimuli in PDLCs and osteocytes. (3) Cell activation and differentiation: the activation and differentiation mechanisms of osteoblast and osteoclast, the force-induced sterile inflammation, and the communication networks consisting of sensors and effectors. (4) Tissue remodeling: the remodeling of bone and periodontal ligament (PDL) in the compression side and tension side responding to mechanical stimuli and root resorption. Lastly, we talked about the clinical implications of the updated OTM mechanisms, regarding optimal orthodontic force (OOF), acceleration of OTM, and prevention of root resorption.

Nanoparticles for the gene therapy field have seen remarkable progress over the last 10 years; however, low delivery efficiency and other reasons impede the clinical translation of nanocarriers. Therefore, a summary of hotspots and trends in this field is needed to promote further research development. In this research, from 2011 to 2021, 1,221 full records and cited references of Web of Science–indexed manuscripts regarding nanoparticle-targeted delivery systems have been analyzed by CiteSpace, VOSviewer, and MapEquation. In these software, keywords co-occurrence networks, alluvial diagram, co-citation networks, and structural variation analysis were carried out to emphasize the scientific community’s focus on nanomedicine of targeted delivering of nucleic acids. Keywords such as transfection efficiency, tumor cell, membrane antigen, and siRNA delivery were highlighted in the density map from VOSviewer. In addition, an alluvial flow diagram was constructed to detect changes in concepts. In the co-citation network, cluster 1 (exosomes) and cluster 17 (genome editing) were new research fields, and the efforts in modifying nanoparticles were revealed in the structural variation analysis. Aptamer and SELEX (systematic evolution of ligands by exponential enrichment) represented a helpful system in targeted delivery. These results indicated that the transfection efficiency of nanocarriers required continuous improvements. With the approval of several nucleic acid drugs, a new content of nanoparticle carriers is to introduce gene-editing technology, especially CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR–associated protein 9). In addition, exosomes have great potential as targeted nanoparticles. By mapping the knowledge domains of nanomedicine in targeted delivering of nucleic acids, this study analyzed the intellectual structure of this domain in the recent 10 years, highlighting classical modifications on nanoparticles and estimating future trends for researchers and decision-makers interested in this field.

The bacterial effector MavC can ubiquitinate the host E2 enzyme UBE2N to dampen the host immune response. Here, the authors provide mechanistic insight into this non-canonical ubiquitination machinery and reveal the structural basis for the functional differences between MavC and its close homolog MvcA.

Objective: The introduction of therapeutic antibodies (tAbs) into clinical practice has revolutionized tumor treatment strategies, but their tumor therapy efficiency is still far below expectations because of the rapid degradation and limited tumor accumulation of tAbs. Methods: We developed a nanocapsule-based delivery system to induce the self-augmentation of the enhanced permeability and retention (EPR) effect. This system constantly penetrated across the blood-tumor barrier into the tumor while avoiding the attack of tAbs by the immune system. The biodistribution and therapeutic effect were tested with single dose administration of nanocapsule-tAbs in vivo. Results: The accumulation of Nano(cetuximab) within subcutaneous PC9 tumors was gradually enhanced over 6 days after single dose administration, which was contrary to the biodistribution of native cetuximab. Nano(cetuximab) accumulated in tumor tissues via the EPR effect and released cetuximab. The released cetuximab acted on vascular endothelial cells to destroy the blood-tumor barrier and induce self-augmentation of the EPR effect, which in turn contributed to further tumor accumulation of long-circulating Nano(cetuximab). Compared with single dose administration of native cetuximab, Nano(cetuximab) showed an effective tumor suppressive effect for 3 weeks. Conclusions: The nanocapsule-based delivery system efficiently delivered tAbs to tumor tissues and released them to boost the EPR effect, which facilitated further tumor accumulation of the tAbs. This novel self-augmentation of the EPR effect facilitated by the biological characteristics of tAbs and nanotechnology contributed to the improvement of the therapeutic effect of tAbs, and stimulated new ideas for antibody-based tumor therapy.

Leadership plays a significant role in the performance of individuals and organizations. This paper investigates the impact of leadership styles on the innovative performance of female leaders in Pakistani Universities using a survey approach. This paper aimed to (a) discover a leadership style practiced by females and (b) discover the relationship between leadership style and the innovative performance of female leaders. Several female leaders, including faculty members, heads of departments, deans, coordinators, and directors, from public and private universities of Punjab (a province of Pakistan), were involved in this study. A sample of one hundred female leaders was selected using a multistage sampling method. In the first stage, five public and five private sector universities were selected through a simple random method. In the second stage, ten female leaders (five from each of the social science and basic science departments) were selected from each university through a purposive sampling method. The researchers adopted a reliable instrument to collect the survey data. The collected data were analyzed using SPSS (Version 26). Mean scores and Pearson correlation coefficients were used to discover the relationship between various variables. The investigation revealed that most female leaders practice the transactional leadership style in their universities. This study also discovered a moderate positive relationship between both leadership styles, namely transactional and transformational, and innovative performance. The study recommends that various workshops and seminars may be conducted to increase the practices of both leadership styles to enhance innovation in Pakistani Universities.

Abstract Epitranscriptome profiling using MeRIP-seq is a powerful technique for in vivo functional studies of reversible RNA modifications. We develop RADAR, a comprehensive analytical tool for detecting differentially methylated loci in MeRIP-seq data. RADAR enables accurate identification of altered methylation sites by accommodating variability of pre-immunoprecipitation expression level and post-immunoprecipitation count using different strategies. In addition, it is compatible with complex study design when covariates need to be incorporated in the analysis. Through simulation and real dataset analyses, we show that RADAR leads to more accurate and reproducible differential methylation analysis results than alternatives, which is available at https://github.com/scottzijiezhang/RADAR.

ObjectivesTo date, radiomics has been applied in oncology for over a decade and has shown great progress. We used a bibliometric analysis to analyze the publications of radiomics in oncology to clearly illustrate the current situation and future trends and encourage more researchers to participate in radiomics research in oncology.MethodsPublications for radiomics in oncology were downloaded from the Web of Science Core Collection (WoSCC). WoSCC data were collected, and CiteSpace was used for a bibliometric analysis of countries, institutions, journals, authors, keywords, and references pertaining to this field. The state of research and areas of focus were analyzed through burst detection.ResultsA total of 7,199 pieces of literature concerning radiomics in oncology were analyzed on CiteSpace. The number of publications has undergone rapid growth and continues to increase. The USA and Chinese Academy of Sciences are found to be the most prolific country and institution, respectively. In terms of journals and co-cited journals, Scientific Reports is ranked highest with respect to the number of publications, and Radiology is ranked highest among co-cited journals. Moreover, Jie Tian has published the most publications, and Phillipe Lambin is the most cited author. A paper published by Gillies et al. presents the highest citation counts. Artificial intelligence (AI), segmentation methods, and the use of radiomics for classification and diagnosis in oncology are major areas of focus in this field. Test-retest statistics, including reproducibility and statistical methods of radiomics research, the relation between genomics and radiomics, and applications of radiomics to sarcoma and intensity-modulated radiotherapy, are frontier areas of this field.ConclusionTo our knowledge, this is the first study to provide an overview of the literature related to radiomics in oncology and may inspire researchers from multiple disciplines to engage in radiomics-related research.

Abstract Fluorescent silk is fundamentally important for the development of future tissue engineering scaffolds. Despite great progress in the preparation of a variety of colored silks, fluorescent silk with enhanced mechanical properties has yet to be explored. In this study, we report on the fabrication of intrinsically super-strong fluorescent silk by feeding Bombyx mori silkworm carbon nanodots (CNDs). The CNDs were incorporated into silk fibroin, hindering the conformation transformation, confining crystallization, and inducing orientation of mesophase. The resultant silk exhibited super-strong mechanical properties with breaking strength of 521.9 ± 82.7 MPa and breaking elongation of 19.2 ± 4.3%, improvements of 55.1% and 53.6%, respectively, in comparison with regular silk. The CNDs-reinforced silk displayed intrinsic blue fluorescence when exposed to 405 nm laser and exhibited no cytotoxic effect on cells, suggesting that multi-functional silks would be potentially useful in bioimaging and other applications.

To control the spread of coronavirus disease 2019 (COVID-19), it is effective to perform a fast screening of the respiratory rate of the subject at the gate before entering a space to assess the potential risks. In this paper, we examine the potential of a novel yet cost-effective solution, called thermopile-based respiratory gating, to contactlessly screen a subject by measuring their respiratory rate in the scenario with an entrance gate. Based on a customized thermopile array system, we investigate different image and signal processing methods that measure respiratory rate from low-resolution thermal videos, where an automatic region-of-interest selection-based approach obtains a mean absolute error (MAE) of 0.8 breaths per minute. We show the feasibility of thermopile-based respiratory gating and quantify its limitations and boundary conditions in a benchmark (e.g., appearance of face mask, measurement distance and screening time). The technical validation provided by this study is helpful for designing and implementing a respiratory gating solution toward the prevention of the spread of COVID-19 during the pandemic.

Establishment of a functional vascular network, which is required in tissue repair and regeneration, needs large-scale production of specific arterial or venous endothelial cells (ECs) from stem cells. Previous in vitro studies by us and others revealed that shear stress induces EC differentiation of bone marrow-derived mesenchymal stem cells and embryonic stem cells. In this study, we focused on the impact of different magnitudes of shear stress on the differentiation of mouse-induced pluripotent stem cells (iPSCs) towards arterial or venous ECs. When iPSCs were exposed to shear stress (5, 10, and 15 dyne/cm2) with 50 ng/mL vascular endothelial growth factor and 10 ng/mL fibroblast growth factor, the expression levels of the general EC markers and the arterial markers increased, and the stress amplitude of 10 dyne/cm2 could be regarded as a proper promoter, whereas the venous and lymphatic markers had little or no expression. Further, shear stress caused cells to align parallel to the direction of the flow, induced cells forming functional tubes, and increased the secretion of nitric oxide. In addition, Notch1 was significantly upregulated, and the Notch ligand Delta-like 4 was activated in response to shear stress, while inhibition of Notch signaling by DAPT remarkably abolished the shear stress-induced arterial epithelium differentiation. Taken together, our results indicate that exposure to appropriate shear stress facilitated the differentiation of mouse iPSCs towards arterial ECs via Notch signaling pathways, which have potential applications for both disease modeling and regenerative medicine.

Retinoid x receptor α (RXRα) is abundantly expressed in the liver and is essential for the function of other nuclear receptors. Using chromatin immunoprecipitation sequencing and mRNA profiling data generated from wild type and RXRα-null mouse livers, the current study identifies the bona-fide hepatic RXRα targets and biological pathways. In addition, based on binding and motif analysis, the molecular mechanism by which RXRα regulates hepatic genes is elucidated in a high-throughput manner.Close to 80% of hepatic expressed genes were bound by RXRα, while 16% were expressed in an RXRα-dependent manner. Motif analysis predicted direct repeat with a spacer of one nucleotide as the most prevalent RXRα binding site. Many of the 500 strongest binding motifs overlapped with the binding motif of specific protein 1. Biological functional analysis of RXRα-dependent genes revealed that hepatic RXRα deficiency mainly resulted in up-regulation of steroid and cholesterol biosynthesis-related genes and down-regulation of translation- as well as anti-apoptosis-related genes. Furthermore, RXRα bound to many genes that encode nuclear receptors and their cofactors suggesting the central role of RXRα in regulating nuclear receptor-mediated pathways.This study establishes the relationship between RXRα DNA binding and hepatic gene expression. RXRα binds extensively to the mouse genome. However, DNA binding does not necessarily affect the basal mRNA level. In addition to metabolism, RXRα dictates the expression of genes that regulate RNA processing, translation, and protein folding illustrating the novel roles of hepatic RXRα in post-transcriptional regulation.

We investigated the effect of photodynamic therapy (PDT) and of an anti-vascular cell adhesion molecule-1 (VCAM-1) monoclonal antibody on the in vivo growth of C6 glioma. Seven days after inoculation with C6 cells, adult male Wistar rats weighing 280-300 g with MRI-confirmed glioma were randomly assigned to 4 groups (N = 15 per group): PDT + VCAM-1 antibody group; PDT group; VCAM-1 antibody group; control group. Eight days after inoculation, hematoporphyrin monomethyl ether (HMME) was administered as a photosensitizer and PDT was performed at 630 nm (illumination intensity: 360 J/cm²) for 10 min. VCAM-1 antibody (50 µg/mL) was then administered (0.5 mL) through the tail vein every other day from day 8 to day 16. At day 21, 5 rats in each group were sacrificed and cancers were harvested for immunohistochemistry and Western blot assay for the detection of VCAM-1, and TUNEL assay was used to detect apoptosis. Survival and tumor volume were recorded in the remaining 10 rats in each group. In the PDT group, tumor growth was significantly suppressed (67.2%) and survival prolonged (89.3%), accompanied by an increase in apoptosis (369.5%), when compared to control. Furthermore, these changes were more pronounced in the PDT + VCAM-1 antibody group. After PDT, VCAM-1 expression was markedly increased (121.8%) and after VCAM-1 monoclonal antibody treatment, VCAM-1 expression was significantly reduced (58.2%). PDT in combination with VCAM-1 antibody can significantly inhibit the growth of C6 glioma and prolong survival. This approach may represent a promising strategy in the treatment of glioma.