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This study investigates the hot compression behavior of a molybdenum- Rhenium (Mo–Re) alloy, focusing on deformation mechanisms and instability. Utilizing electron backscattered diffraction (EBSD) and transmission electron microscope (TEM), we characterized the microstructure, grain orientation, and deformation behavior across temperatures (650, 750, 850, and 950 °C) and strain rates (0.01, 0.1, 1, and 10s-1). The study reveals that Mo–Re alloys exhibit high hot deformation resistance, necessitating optimal processing conditions for effective plastic deformation. Key findings by EBSD and TEM include the formation of dislocation networks and substructures enhancing grain plasticity. We established a constitutive equation and processing maps, providing valuable insights for industrial applications and future alloy development.

Abstract Background The purpose of this study was to review echocardiography-based diagnosis of persistent fifth aortic arch (PFAA) in children. Methods From January 2015 to December 2022, we retrospectively analyzed the echocardiographic findings and the relevant clinical data during follow-up of patients with PFAA who were treated in the Third Affiliated Hospital of Zhengzhou University. The diagnosis was confirmed by computed tomography angiography or surgery. Results Seven PFAA cases included two Weinberg type A and five Weinberg type B. The anatomical details of PFAA were assessed using a combination of the long-axis view of the left ventricular outflow tract (from the left high parasternal window) and the long-axis view of the aortic arch (from the suprasternal window). In Weinberg type A, the distal fifth and fourth aortic arches were connected to the descending aorta, which was associated with aortic coarctation. In Weinberg type B, the upper arch of the fourth aorta was interrupted, and only the lower arch of the fifth aorta was connected to the descending aorta. Surgical repair of PFAA was indicated in five patients with blood flow disruption, among which four had good postoperative results and one refused surgery. Two patients with unobstructed PFAA blood flow required follow-up rather than surgery. Conclusions It is feasible to diagnose PFAA by echocardiography. Combined application of the high parasternal left ventricular outflow tract view and the suprasternal aortic arch view can improve timely detection of different types of PFAA in children.

Abstract Background COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an unprecedented world pandemic, leading to a global human health crisis. Although SARS CoV-2 mainly affects the lungs, causing interstitial pneumonia and severe acute respiratory distress syndrome, a number of patients often have extensive clinical manifestations, such as gastrointestinal symptoms, cardiovascular damage and renal dysfunction. Purpose This review article discusses the pathogenic mechanisms of cardiovascular damage in COVID-19 patients and provides some useful suggestions for future clinical diagnosis, treatment and prevention. Methods An English-language literature search was conducted in PubMed and Web of Science databases up to 12th April, 2024 for the terms “COVID-19”, “SARS CoV-2”, “cardiovascular damage”, “myocardial injury”, “myocarditis”, “hypertension”, “arrhythmia”, “heart failure” and “coronary heart disease”, especially update articles in 2023 and 2024. Salient medical literatures regarding the cardiovascular damage of COVID-19 were selected, extracted and synthesized. Results The most common cardiovascular damage was myocarditis and pericarditis, hypertension, arrhythmia, myocardial injury and heart failure, coronary heart disease, stress cardiomyopathy, ischemic stroke, blood coagulation abnormalities, and dyslipidemia. Two important pathogenic mechanisms of the cardiovascular damage may be direct viral cytotoxicity as well as indirect hyperimmune responses of the body to SARS CoV-2 infection. Conclusions Cardiovascular damage in COVID-19 patients is common and portends a worse prognosis. Although the underlying pathophysiological mechanisms of cardiovascular damage related to COVID-19 are not completely clear, two important pathogenic mechanisms of cardiovascular damage may be the direct damage of the SARSCoV-2 infection and the indirect hyperimmune responses.

Abstract Cardiovascular diseases (CVDs) have emerged as a predominant threat to human health, surpassing the incidence and mortality rates of neoplastic diseases. Extracellular vesicles (EVs) serve as vital mediators in intercellular communication and material exchange. Endothelial progenitor cells (EPCs), recognized as precursors of vascular endothelial cells (ECs), have garnered considerable attention in recent years due to the potential therapeutic value of their derived extracellular vesicles (EPC-EVs) in the context of CVDs. This comprehensive review systematically explores the origins, characteristics, and functions of EPCs, alongside the classification, properties, biogenesis, and extraction techniques of EVs, with particular emphasis on their protective roles in CVDs. Additionally, we delve into the essential bioactive components of EPC-EVs, including microRNAs, long non-coding RNAs, and proteins, analyzing their beneficial effects in promoting angiogenesis, anti-inflammatory and anti-oxidant activities, anti-fibrosis, anti-apoptosis, and myocardial regeneration. Furthermore, this review comprehensively investigates the therapeutic potential of EPC-EVs across various CVDs, encompassing acute myocardial infarction, myocardial ischemia–reperfusion injury, atherosclerosis, non-ischemic cardiomyopathies, and diabetic cardiovascular disease. Lastly, we summarize the potential challenges associated with the clinical application of EPC-EVs and outline future directions, aiming to offer a valuable resource for both theoretical insights and practical applications of EPC-EVs in managing CVDs.

Objective To explore the diagnostic value of platelet long non-coding RNA (lncRNA) as a biomarker for early screening of lung adenocarcinoma (LUAD). Methods The GSE183635 and GSE89843 datasets, which contained the platelet transcriptome of LUAD and healthy controls, were used for differential analysis, and the intersection of the differentially expressed lncRNA(DElncRNA) of the two datasets was taken. The expression levels of DElncRNA in LUAD tissues and normal control tissues were analyzed using GEPIA2. The expression levels of LINC01088 in platelets of 51 healthy controls and 54 LUAD patients were detected by quantitative Real-time PCR (qRT-PCR), and the diagnostic ability of each index was evaluated by ROC curve. Results 8 DElncRNAs and 1 265 DElncRNAs were obtained from GSE183635 and GSE89843 datasets, respectively. The key DElncRNA LINC01088 was selected after intersection. GEPIA2 analysis showed that the expression level of LINC01088 in LUAD tissues was lower than that in normal lung tissues (P

Abstract Background The relationship between the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphism (SNP) and serum homocysteine (Hcy) levels or H-type hypertension in different populations is inconsistent. This study aimed to explore the association between the MTHFR rs1801133 SNP and serum Hcy levels of Zhuang hypertensive patients in the central region of Guangxi. Methods A total of 606 Zhuang inpatients with essential hypertension were recruited in our hospital from August 2016 to December 2018. The patients were divided into H-type hypertension (Hcy > 10 µmol/L, n = 528) and non–H-type hypertension (Hcy ≤ 10 µmol/L, n = 78) groups. At the same time, an age- and sex-matched group of 379 subjects with normal physical examination in our hospital were selected as the control group. Blood biochemical measurements and genotyping of the MTHFR rs1801133 SNP were performed. Results The prevalence of H-type hypertension was 87.13%. The levels of serum Hcy in patients with hypertension were higher than those in control group (14.20 ± 5.78 μmol/L vs. 11.97 ± 5.39 μmol/L, P

Summary: The phenotype-first approach (PFA) and data-driven approach (DDA) have both greatly facilitated anthropological studies and the mapping of trait-associated genes. However, the pros and cons of the two approaches are poorly understood. Here, we systematically evaluated the two approaches and analyzed 14,838 facial traits in 2,379 Han Chinese individuals. Interestingly, the PFA explained more facial variation than the DDA in the top 100 and 1,000 except in the top 10 phenotypes. Accordingly, the ratio of heterogeneous traits extracted from the PFA was much greater, while more homogenous traits were found using the DDA for different sex, age, and BMI groups. Notably, our results demonstrated that the sex factor accounted for 30% of phenotypic variation in all traits extracted. Furthermore, we linked DDA phenotypes to PFA phenotypes with explicit biological explanations. These findings provide new insights into the analysis of multidimensional phenotypes and expand the understanding of phenotyping approaches.

Summary: An unprecedented strategy for preparing a series of sulfur ylides through electro-oxidative quinylation of sulfides in batch and continuous flow has been developed. Good to excellent yields were obtained with excellent functional group compatibility and good concentration tolerance under exogenous oxidant- and transition metal-free conditions. Advantageously, this electrosynthesis methodology was scalable with higher daily production and steady production was achieved attributing to the use of micro-flow cells.

Abstract Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/β-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/β-catenin signaling via high expression of LGR6 promoted by HnRNPK.

Highlights Multidimensional detection of intensity, wavelength, polarization, and angle of the incidence light significantly accelerates the development of optical information technology and artificial intelligence fields. The first comprehensive overview of the advancement of multifunctional photodetectors for perovskite semiconductors ranging from polarized light detection, spectral detection, and angle-sensing detection to self-powered detection is summarized. The existing problems and perspectives are discussed which can inspire more researchers to rationally design new perovskite materials and micro/nano-structure for high-performance multifunctional photodetectors.

Liposomes as carriers for CRISPR/Cas9 complexes represent an attractive approach for cardiovascular gene therapy. A critical barrier to this approach remains the efficient delivery of CRISPR-based genetic materials into cardiomyocytes. Echogenic liposomes (ELIP) containing a fluorescein isothiocyanate-labeled decoy oligodeoxynucleotide against nuclear factor kappa B (ELIP-NF-κB-FITC) were used both in vitro on mouse neonatal ventricular myocytes and in vivo on rat hearts to assess gene delivery efficacy with or without ultrasound. In vitro analysis was then repeated with ELIP containing Cas9-sg-IL1RL1 (interleukin 1 receptor-like 1) RNA to determine the efficiency of gene knockdown. ELIP-NF-κB-FITC without ultrasound showed limited gene delivery in vitro and in vivo, but ultrasound combined with ELIP notably improved penetration into heart cells and tissues. When ELIP was used to deliver Cas9-sg-IL1RL1 RNA, gene editing was successful and enhanced by ultrasound. This innovative approach shows promise for heart disease gene therapy using CRISPR technology.

Marginal velopharyngeal inadequacy (MVPI) is a particular status of velopharyngeal closure after cleft palate repair. The physiological and phonological characteristics of patients with MVPI are significantly different from those with typical velopharyngeal insufficiency. The pathological mechanisms and diagnostic criteria of MVPI are still controversial, and there is limited evidence to guide the selection of surgical and non- surgical management options and a lack of recognized standards for treatment protocols. Based on a systematic study of the relevant literatures, this review identifies specific problems that are currently under-recognized in the diagnosis and treatment of MVPI and provides guidelines for further exploration of standardized and reasonable intervention protocols for MVPI.

Oral administration of resveratrol is able to ameliorate the progression of diabetic nephropathy (DN); however, its mechanisms of action remain unclear. Recent evidence suggested that the gut microbiota is involved in the metabolism therapeutics. In the current study, we sought to determine whether the anti-DN effects of resveratrol are mediated through modulation of the gut microbiota using the genetic db/db mouse model of DN. We demonstrate that resveratrol treatment of db/db mice relieves a series of clinical indicators of DN. We then show that resveratrol improves intestinal barrier function and ameliorates intestinal permeability and inflammation. The composition of the gut microbiome was significantly altered in db/db mice compared to control db/m mice. Dysbiosis in db/db mice characterized by low abundance levels of Bacteroides, Alistipes, Rikenella, Odoribacter, Parabacteroides, and Alloprevotella genera were reversed by resveratrol treatment, suggesting a potential role for the microbiome in DN progression. Furthermore, fecal microbiota transplantation, derived from healthy resveratrol-treated db/m mice, was sufficient to antagonize the renal dysfunction, rebalance the gut microbiome and improve intestinal permeability and inflammation in recipient db/db mice. These results indicate that resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol, which provides supporting evidence for the gut-kidney axis in DN.

Abstract Nowadays, obesity is one of the largest public health problems worldwide. In the last few decades, there has been a marked increase in the obesity epidemic and its related comorbidities. Worldwide, more than 2.2 billion people (33%) are affected by overweight or obesity (712 million, 10%) and its associated metabolic complications. Although a high heritability of obesity has been estimated, the genetic variants conducted from genetic association studies only partially explain the variation of body mass index. This has led to a growing interest in understanding the potential role of epigenetics as a key regulator of gene-environment interactions on the development of obesity and its associated complications. Rapid advances in epigenetic research methods and reduced costs of epigenome-wide association studies have led to a great expansion of population-based studies. The field of epigenetics and metabolic diseases such as obesity has advanced rapidly in a short period of time. The main epigenetic mechanisms include DNA methylation, histone modifications, microRNA (miRNA)-mediated regulation and so on. DNA methylation is the most investigated epigenetic mechanism. Preliminary evidence from animal and human studies supports the effect of epigenetics on obesity. Studies of epigenome-wide association studies and genome-wide histone modifications from different biological specimens such as blood samples (newborn, children, adolescent, youth, woman, man, twin, race, and meta-analysis), adipose tissues, skeletal muscle cells, placenta, and saliva have reported the differential expression status of multiple genes before and after obesity interventions and have identified multiple candidate genes and biological markers. These findings may improve the understanding of the complex etiology of obesity and its related comorbidities, and help to predict an individual’s risk of obesity at a young age and open possibilities for introducing targeted prevention and treatment strategies.

It remains a challenge to achieve satisfactory balance between biodegradability and osteogenic capacity in biosynthetic bone grafts. In this study, we aimed to address this challenge by incorporating mesoporous bioactive glass (MBG) into poly(caprolactone-co-glycolide) (PGA-PCL) at gradient ratios. MBG/PGA-PCL (PGC/M) scaffolds with MBG incorporation ratio at 0, 10%, 25% and 40% (PGC/M0-40) were synthesized using a modified solvent casting-particulate leaching method, and their physiochemical and biological properties were comprehensively evaluated. PGC/M scaffolds exhibited highly perforated porous structure with a large-pore size of 300–450 μm, with ordered MBGs of around 6.0 nm mesopores size uniformly dispersed. The increase in MBG incorporation ratio significantly improved the scaffold surface hydrophilicity, apatite-formation ability and pH stability, increased the weight loss rate while insignificantly influenced the molecular chains degradation of PGA-PCL component, and facilitated the attachment, spreading, viability and proliferation of rat bone marrow stromal cells (rBMSCs) on scaffolds. Moreover, rBMSCs cultured on PGC/M10-40 scaffolds demonstrated enhanced ALP activity and osteogenesis-related gene expression in a MBG dose-dependent manner as compared with those cultured on PGC/M0 scaffolds. When implanted to the rat cranial bone defect, PGC/M25 and PGC/M40 scaffolds induced significantly better bone repair as compared to PGC/M0 and PGC/M10 scaffolds. Besides, the biodegradability of PGC/M scaffolds correlated with the MBG incorporation ratio. These data suggested this novel PGC/M scaffolds as promising bone repair biomaterial with highly tunable hydrophilicity, bioactivity, cytocompatibility, osteogenic activity as well as biodegradability.

Summary: Genes that are key to cell identity are generally regulated by cell-type-specific enhancer elements bound by transcription factors, some of which facilitate looping to distant gene promoters. In contrast, genes that encode housekeeping functions, whose regulation is essential for normal cell metabolism and growth, generally lack interactions with distal enhancers. We find that Ronin (Thap11) assembles multiple promoters of housekeeping and metabolic genes to regulate gene expression. This behavior is analogous to how enhancers are brought together with promoters to regulate cell identity genes. Thus, Ronin-dependent promoter assemblies provide a mechanism to explain why housekeeping genes can forgo distal enhancer elements and why Ronin is important for cellular metabolism and growth control. We propose that clustering of regulatory elements is a mechanism common to cell identity and housekeeping genes but is accomplished by different factors binding distinct control elements to establish enhancer-promoter or promoter-promoter interactions, respectively.

Summary: It has been proved that Raman spectral intensities could be used to diagnose lung cancer patients. However, the application of Raman spectroscopy in identifying the patients with pulmonary nodules was barely studied. In this study, we revealed that Raman spectra of serum samples from healthy participants and patients with benign and malignant pulmonary nodules were significantly different. A support vector machine (SVM) model was developed for the classification of Raman spectra with wave points, according to ANOVA test results. It got a good performance with a median area under the curve (AUC) of 0.89, when the SVM model was applied in discriminating benign from malignant individuals. Compared with three common clinical models, the SVM model showed a better discriminative ability and added more net benefits to participants, which were also excellent in the small-size nodules. Thus, the Raman spectroscopy could be a less-invasive and low-costly liquid biopsy.

Abstract Human adipose-derived stem cells (hASCs) are a promising cell type for bone tissue regeneration. Circular RNAs (circRNAs) have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis. However, how circRNAs regulate hASCs in osteogenesis is still unclear. Herein, we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs. Knockdown of circ_0003204 by siRNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs. We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p. We predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 mRNA. The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis. Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model, while overexpression of circ_0003204 inhibited bone defect repair. Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.

A typical ferritic/martensitic (F/M) steel sheet was subjected to pulsed laser surface remelting (LSR) and corrosion test in lead-bismuth eutectic (LBE) at 550 °C. There present two modification zones with distinct microstructures in the LSRed specimen: (1) remelted zone (RZ) consisting of both bulk δ-ferrite grains and martensitic plates and (2) heat-affected zone (HAZ) below the RZ, mainly composed of martensitic plates and high-density precipitates. Martensitic transformation occurs in both the RZ and the HAZ with the Kurdjumov-Sachs and Nishiyama-Wassermann orientation relationships followed concurrently, resulting in scattered orientations and specific misorientation characteristics. Hardnesses of the RZ and the HAZ are 364 ± 7 HV and 451 ± 15 HV, respectively, considerably higher than that of the matrix (267 ± 3 HV). In oxygen-saturated and oxygen-depleted LBE, thicknesses of oxide layers developed on both the as-received and the LSRed specimens increase with prolonging corrosion time (oxide layers always thinner under the oxygen-depleted condition). The corrosion resistance of the LSRed F/M steel in oxygen-saturated LBE is improved, which can be attributed to the grain-refinement accelerated formation of dense Fe–Cr spinel. In oxygen-depleted LBE, the growth of oxide layers is very low with both types of specimens showing similar corrosion resistance.

Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota. However, the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations. A well-controlled environment is thus necessary to reduce undesirable confounding effects, and recapitulate age-dependent changes in the gut microbiota of healthy primates. Herein we performed 16S rRNA gene sequencing, characterized the age-associated gut microbial profiles from infant to elderly crab-eating macaques reared in captivity, and systemically revealed the lifelong dynamic changes of the primate gut microbiota. While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium, the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants, underlining their potential role in host development. Importantly, topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity, and its tremendous decline with age could probably be linked to healthy aging. Moreover, we identified key driver microbes responsible for such age-dependent network changes, which were further linked to altered metabolic functions of lipids, carbohydrates, and amino acids, as well as phenotypes in the microbial community. The current study thus demonstrates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota, and provides new insights into their roles in the development and healthy aging of their hosts.

Objectives. To investigate the association between quantitative parameters generated using synthetic magnetic resonance imaging (SyMRI) and diffusion-weighted imaging (DWI) and Ki-67 expression level in patients with invasive ductal breast cancer (IDC). Method. We retrospectively reviewed the records of patients with IDC who underwent SyMRI and DWI before treatment. Precontrast and postcontrast relaxation times (T1, longitudinal; T2, transverse), proton density (PD) parameters, and apparent diffusion coefficient (ADC) values were measured in breast lesions. Univariate and multivariate regression analyses were performed to screen for statistically significant variables to differentiate the high (≥30%) and low (

Abstract Aim To understand the social network status of older adults with type 2 diabetes mellitus (T2DM) in Beijing, China and explore its related factors. Design A cross‐sectional survey using a sample of convenience was conducted. Methods From April to September 2019, Lubben Social Network Scale‐6 (LSNS‐6) was used to evaluate the social network of 300 older adults with T2DM from the outpatient and inpatient departments of three hospitals and five communities in Beijing. Self‐designed demographics and clinical sheets, Summary of Diabetes Self‐Care Activities Scale, Social Support Rating Scale and Geriatric Depression Scale‐15 were used to investigate the related factors of their social networks. The Equator Research Checklist used in this study is STROBE checklist. Results The score of LSNS‐6 of the older adults was 16.75 ± 7.02 (scale: 0 ~ 30), the score of family network dimension was 8.32 ± 3.63 (scale: 0 ~ 15), and friends network dimension was 8.43 ± 4.74 (scale: 0 ~ 15). Additionally, 22.67% of the older adults had social isolation. Social support, medical payment, self‐assessed health status, residential arrangement and smoking status were associated with the social network level of the older adults with T2DM (p

The CRISPR-based genome editing technology, known as clustered regularly interspaced short palindromic repeats (CRISPR), has sparked renewed interest in gene therapy. This interest is accompanied by the development of single-guide RNAs (sgRNAs), which enable the introduction of desired genetic modifications at the targeted site when used alongside the CRISPR components. However, the efficient delivery of CRISPR/Cas remains a challenge. Successful gene editing relies on the development of a delivery strategy that can effectively deliver the CRISPR cargo to the target site. To overcome this obstacle, researchers have extensively explored non-viral, viral, and physical methods for targeted delivery of CRISPR/Cas9 and a guide RNA (gRNA) into cells and tissues. Among those methods, liposomes offer a promising approach to enhance the delivery of CRISPR/Cas and gRNA. Liposomes facilitate endosomal escape and leverage various stimuli such as light, pH, ultrasound, and environmental cues to provide both spatial and temporal control of cargo release. Thus, the combination of the CRISPR-based system with liposome delivery technology enables precise and efficient genetic modifications in cells and tissues. This approach has numerous applications in basic research, biotechnology, and therapeutic interventions. For instance, it can be employed to correct genetic mutations associated with inherited diseases and other disorders or to modify immune cells to enhance their disease-fighting capabilities. In summary, liposome-based CRISPR genome editing provides a valuable tool for achieving precise and efficient genetic modifications. This review discusses future directions and opportunities to further advance this rapidly evolving field.

Xenon (Xe) has shown great potential as a stroke treatment due to its exceptional ability to protect brain tissue without inducing side effects. We have previously developed Xe-loaded liposomes for the ultrasound-activated delivery of Xe into the cerebral region and demonstrated their therapeutic efficacy. At present, the sole FDA-approved thrombolytic agent for stroke treatment is recombinant tissue plasminogen activator (rtPA). In this study, we aimed to investigate the potential of combining Xe-liposomes with an intravenous rtPA treatment in a clinically relevant embolic rat stroke model. We evaluated the combinational effect using an in vitro clot lysis model and an in vivo embolic middle cerebral artery occlusion (eMCAO) rat model. The treatment groups received intravenous administration of Xe-liposomes (20 mg/kg) at 2 h post-stroke onset, followed by the administration of rtPA (10 mg/kg) at either 2 or 4 h after the onset. Three days after the stroke, behavioral tests were conducted, and brain sections were collected for triphenyltetrazolium chloride (TTC) and TUNEL staining. Infarct size was determined as normalized infarct volume (%). Both in vitro and in vivo clot lysis experiments demonstrated that Xe-liposomes in combination with rtPA resulted in effective clot lysis comparable to the treatment with free rtPA alone. Animals treated with Xe-liposomes in combination with rtPA showed reduced TUNEL-positive cells and demonstrated improved neurological recovery. Importantly, Xe-liposomes in combination with late rtPA treatment reduced rtPA-induced hemorrhage, attributing to the reduction of MMP9 immunoreactivity. This study demonstrates that the combined therapy of Xe-liposomes and rtPA provides enhanced therapeutic efficacy, leading to decreased neuronal cell death and a potential to mitigate hemorrhagic side effects associated with late rtPA treatment.

Emerging smart cities and digital twins are currently built from heterogenous cutting-edge low-power remote sensing systems limited by diverse inefficient communication and information technologies. Future smart cities delivering time-critical services and responses must transition towards utilizing massive numbers of sensors and more efficient integrated systems that rapidly communicate intelligent self-adaptation for collaborative operations. Here, we propose a critical futuristic integrated communication element named City Sensing Base Station (CSBS), inspired by base stations for cell phones that address similar concerns. A CSBS is designed to handle massive volumes of heterogeneous observation data that currently need to be upgraded by middleware or registered. It also provides predictive and interpolation modelling for the control of sensors and response units such as emergency services and drones. A prototype of CSBS demonstrated that it could unify readily available heterogeneous sensing devices, including surveillance video, unmanned aerial vehicles, and ground sensor webs. Collaborative observation capability was also realized by integrating different object detection sources using advanced computer-vision technologies. Experiments with a traffic accident and water pipeline emergency showed sensing and intelligent analyses were greatly improved. CSBS also significantly reduced redundant Internet connections while maintaining high efficiency. This innovation successfully integrates high-density, high-diversity, and high-precision sensing in a distributed way for the future digital twin of cities.

Abstract Background Genetic polymorphisms in the PPARD and NOS1AP is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This study was designed to investigate a potential association of PPARD rs2016520 (T/C) and NOS1AP rs12742393 (A/C) polymorphisms with efficacy of nateglinide in newly diagnosed Chinese patients with type 2 diabetes mellitus (T2DM). Methods Sixty patients with newly diagnosed T2DM were enrolled to identify PPARD rs2016520 and NOS1AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay (PCR–RFLP). All subjects were treated with nateglinide (360 mg/day) for 8 weeks. Anthropometric measurements, clinical laboratory tests were obtained at baseline and after 8 weeks of nateglinide treatment. Results After nateglinide treatment for 8 consecutive weeks, patients with at least one C allele of PPARD rs2016520 showed a smaller decrease in post plasma glucose (PPG), homeostasis model assessment for beta cell function (HOMA-B) than those with the TT genotype did (P

Osteoporosis is a widely distributed disease that may cause complications such as accelerated tooth movement, bone resorption, and tooth loss during orthodontic treatment. Promoting bone formation and reducing bone resorption are strategies for controlling these complications. For several decades, the autophagy inducer lithium chloride (LiCl) has been explored for bipolar . In this study, we investigated the autophagy-promoting effect of LiCl on bone remodeling under osteoporotic conditions during tooth movement. Ovariectomy was used to induce osteoporosis status in vivo. The results showed that LiCl rejuvenated autophagy, decreased apoptosis, and promoted bone formation, thus protecting tooth movement in osteoporotic mice. Furthermore, in vitro experiments showed that LiCl reversed the effects of ovariectomy on bone marrow-derived mesenchymal stem cells (BMSCs) extracted from ovariectomized mice, promoting osteogenesis and suppressing apoptosis by positively regulating autophagy. These findings suggest that LiCl can significantly decrease adverse effects of osteoporosis on bone remodeling, and that it has great potential significance in the field of bone formation during tooth movement in osteoporosis patients.

Atherosclerosis is a complex, multi-stage disease characterized by pathological changes across the vascular wall. Endothelial dysfunction, inflammation, hypoxia, and vascular smooth muscle cell proliferation contribute to its progression. An effective strategy capable of delivering pleiotropic treatment to the vascular wall is essential to limit neointimal formation. Echogenic liposomes (ELIP), which can encapsulate bioactive gases and therapeutic agents, have the potential to deliver enhanced penetration and treatment efficacy for atherosclerosis. In this study, liposomes loaded with nitric oxide (NO) and rosiglitazone, a peroxisome proliferator-activated receptor agonist, were prepared using hydration, sonication, freeze-thawing, and pressurization. The efficacy of this delivery system was evaluated in a rabbit model of acute arterial injury induced by balloon injury to the common carotid artery. Intra-arterial administration of rosiglitazone/NO co-encapsulated liposomes (R/NO-ELIP) immediately following injury resulted in reduced intimal thickening after 14 days. The anti-inflammatory and anti-proliferative effects of the co-delivery system were investigated. These liposomes were echogenic, enabling ultrasound imaging to assess their distribution and delivery. R/NO-ELIP delivery exhibited a greater attenuation (88 ± 15%) of intimal proliferation when compared to NO-ELIP (75 ± 13%) or R-ELIP (51 ± 6%) delivery alone. The study demonstrates the potential of echogenic liposomes as a promising platform for ultrasound imaging and therapeutic delivery.

Large-size primary MC carbides can significantly reduce the performance of M2 high-speed steel. To better control the morphology and size of primary MC carbides, the effect of melting rate on microsegregation and primary MC carbides of M2 steel during electroslag remelting was investigated. When the melting rate is decreased from 2 kg·min-1 to 0.8 kg·min-1, the columnar dendrites are gradually coarsened, and the extent of segregation of Mo and V is alleviated, while the segregation of Cr becomes severe. At 2 kg·min-1, the number of primary MC carbides per unit area with the sizes in the range of 2 μm to 6 μm accounts for about 75% of all MC carbides, while the carbides are mainly concentrated on the size larger than 8 μm at 0.8 kg·min-1. Thermodynamic calculations based on the Clyne-Kurz (simplified to C-K) model shows that MC carbide can be precipitated in the final solidification stage and a smaller secondary dendrite arm spacing caused by higher melting rate (2 kg·min-1 in this experiment) facilitates the refinement of primary MC carbides.

Objective(s): Sirt3 may regulate ROS production and might be involved in β‑cell apoptosis, which plays an important role in the progression of type 2 diabetes mellitus (T2DM). Quercetin is a potent anti-oxidative bioflavonoid, but its effects on T2DM remain to be explored. This study aimed to investigate the effects of quercetin on β‑cell apoptosis and explore its mechanisms.Materials and Methods: The effects of quercetin were conducted on db/db mice and INS1 cells. Fasting blood glucose was determined by the colorimetric method, serum insulin was measured by enzyme‑linked immunosorbent assay (ELISA). Meanwhile, Sirt3 in INS1 cells was knocked down by plasmid transfection. The antioxidant proteins (SOD2 and CAT), apoptosis proteins (cleaved Caspase-3, Bax, and BCL-2), and Sirt3 protein in pancreases and INS1 cells were determined by western blotting. Results: When INS1 cells and diabetic mice were treated with quercetin, the levels of SOD2, CAT, and Sirt3 proteins were increased, the levels of cleaved Caspase-3 and the ratio of Bax to BCL-2 were decreased at different degrees, along with reduced blood glucose levels and elevated insulin levels in diabetic mice. When Sirt3 was knocked down in INS1 cells, increase of two antioxidants and decrease of cell apoptosis generated by quercetin could not occur. Conclusion: Quercetin protected islet β‑cells from oxidation-induced apoptosis via Sirt3 in T2DM, which would be beneficial to develop new strategies for preventing β‑cell failure in T2DM.

Posterior pharyngeal flap palatoplasty (PPF) is one of the most commonly used surgical procedures to correct speech, especially for patients suffering from velopharyngeal insufficiency (VPI). During PPF, surgeons use the catheter to control the lateral velopharyngeal port on each side. Airway obstruction and sleep apnea are common after PPF. To understand the air dynamics of the upper airway after PPF, we used computational fluid dynamics (CFD) to demonstrate the airflow. In our previous study, we have revealed the expiration process of the upper airway after PPF and shown the features of how PPF successfully restores the oral pressure for speech. In this study, we focus on examining the inspiration process. Normal airway structures were included. For the normal velopharyngeal structure, one cylinder was applied to each model. For recapitulating the velopharyngeal structure after PPF, two cylinders were used in each model. The ports for borderline/inadequate closure, which can help the oral cavity get the required pressure, were chosen for this study. A real-time CFD simulation was used to capture the airflow through the ports. We found that the airflow dynamics of the upper airway’s inspiration were dependent on the velopharyngeal structure. Although the airflow patterns were similar, the velocities between one-port and two-port structures were different, which explained why patients after PPF breathed harder than before and suggested that the one-port structure might be a better choice for secondary VPI reconstruction based on the CFD analyses.

The associations among the EH domain-binding protein 1 (EHBP1), tubulin beta class I (TUBB), and WW domain-containing oxidoreductase (WWOX) single nucleotide polymorphisms (SNPs) and coronary artery disease (CAD) and ischemic stroke (IS) are not yet understood. This study aimed to detect the associations of these SNPs, gene-gene and gene-environment interactions and CAD and IS in the Guangxi Han population. A total of 1853 unrelated subjects were recruited into normal control (n = 638), CAD (n = 622), and IS (n = 593) groups. Related genotypes were determined by high-throughput sequencing. The genotypic and minor allelic frequencies of rs2278075 were different between the CAD and control groups, and those of rs2710642, rs3130685, and rs2278075 were also different between the IS and control groups. The rs2278075T allele, rs3130685-rs2222896-rs2278075, rs3130685-rs2222896-diabetes, rs3130685-rs2222896-drinking, and haplotype rs2710642A-rs10496099C-diabetes interactions were associated with increased risk, while G-T-G-C-G-A and G-T-T-T-G-T-drinking were associated with reduced risk of CAD. The rs2278075T and rs2710642G alleles, rs2710642G-rs10496099C haplotype, rs3130685-rs2278075-rs2222896, and rs2710642-rs2278075-hypertension interactions aggravated the association with IS, whereas the rs3130685T allele, rs2710642A-rs10496099C haplotype and the interactions of H1 (s2710642A-rs10496099C)-H2 (rs2710642G-rs10496099C)-drinking and I1 (A-C-G-C-A-A)-I3 (A-C-G-T-A-A)-I4 (A-C-G-T-G-A)-I5 (G-T-G-C-G-A) diminished the association with IS. Carrying WWOX rs2278075T was strongly associated with CAD or IS, while EHBP1 rs2710642 and TUBB rs3130685 might alter the association of IS by modifying the serum lipid profile. This study demonstrates that the EHBP1, TUBB, and WWOX SNPs, gene-gene and gene-environment interactions are associated with the risk of CAD and IS in the Guangxi Han population.

Abstract Background The current research was to assess the relationship of the solute carrier family 44 member 4 (SLC44A4) rs577272, notch receptor 4 (NOTCH4) rs3134931 SNPs and serum lipid levels in the Han and Maonan ethnic groups. Methods The genetic makeup of the SLC44A4 rs577272 and NOTCH4 rs3134931 SNPs in 2467 unrelated subjects (Han, 1254; Maonan,1213) was obtained by using polymerase chain reaction and restriction fragment length polymorphism technique, combined with gel electrophoresis, and confirmed by direct sequencing. Results The genotype frequencies of SLC44A4 rs577272 and NOTCH4 rs3134931 SNPs were different between Han and Maonan populations (P 50%) in both Han and Maonan groups. The haplotype of rs577272G-rs3134931A was associated with TG and HDL-C in Han; and TC, TG and HDL-C in Maonan ethnic groups. Conclusions These results suggest that the relationship among SLC44A4 rs577272, NOTCH4 rs3134931 SNPs and serum lipid parameters may vary depending on the gender and/or ethnicity/race in some populations. Haplotypes could explain more changes in serum lipid parameters than any single SNP alone particularly for TC, TG and HDL-C.

An 800 MPa class high strength low-alloy (HSLA) steel block part was deposited on substrate with similar composition by gas metal arc welding (GMAW)-based wire arc additive manufacturing (WAAM). The base plate could be removed after deposition or retained as part of the additive manufacturing (AM) part, forming the hybrid additive manufacturing (HAM) part. Tensile tests of the AM part and the HAM part were performed at ambient temperature (AT) and elevated temperature (ET, 600°C held for 4 h) for potential applications in high-rise buildings. Microstructure observations and low temperature impact tests were also conducted. Results show that microstructure of the deposit mainly consists of lower bainite and granular bainite. AT yield strength (YS) of the deposit along the deposition, transverse, and vertical directions is ∼770 MPa. ET YS of the deposit along the lateral and building directions could reach 373 MPa, 48.4% of the AT YS. Fracture elongation along all directions could exceed 18.0% for both AT and ET. Low temperature (−50°C) impact absorbed energy of the deposit could exceed 84 J along all directions. Mechanical properties of the HAM part are similar or superior to those of the AM part along the vertical direction, except the AT fracture elongation, which is one-fifth lower. Good strength-ductility-toughness balance of the made part verified the feasibility of using WAAM to manufacture 800 MPa HSLA steel block parts that have potential applications in high-rise buildings, especially considering ET YS of the part might be improved by alloying redesign to meet the performance requirements of building steel.

Abstract Background Little is known about the correlation between the melanocortin 4 receptor gene (MC4R) single nucleotide polymorphisms (SNPs) and the risk of obesity. This research sought to test the MC4R rs17782313, rs476828 and rs12970134 SNPs, their haplotypes and gene-environment interactions on the risk of obesity in the Maonan ethnic group, an isolated minority in China. Methods A case-control study comprised of 1836 participants (obesity group, 858; and control group, 978) was conducted. Genotypes of the three SNPs were determined by the next-generation sequencing (NGS) technology. Results The genotypic frequencies of the three SNPs were different between the obesity and control groups (P