Microfluidic device reveals new insights into impairment of neutrophil transmigration in patients with sepsis.

Neutrophils need to migrate through tight tissue spaces to eliminate pathogens, but their movement is often hindered by their large and stiff nuclei. Neutrophil migration is impaired in sepsis patients, but it is unclear whether this defect is related to the deformability of their nuclei. Herein, we designed microfluidic devices with micron-scale narrow slits to simulate biological barriers. This setup allowed us to observe and record neutrophil movement and nuclear deformation in real-time. We also developed a method for morphological analysis to quantify nucleus deformation in numerous individual cells. Our studies showed that neutrophils from healthy individuals could adjust their nuclear shape to squeeze through these constrictions, whereas those from sepsis patients demonstrated less flexibility. Neutrophils with rigid nuclei struggled to pass through narrow gaps and were more likely to rupture under pressure. These findings suggest that the migration defects of neutrophils observed in sepsis may be attributed to the inability of neutrophils to deform their nuclei, highlighting the crucial role of microfluidic technologies in offering new insights into migration defects under pathological conditions.

Novel diacylglycerol oil-based nanostructured lipid carriers improves the stability and digestibility of lycopene.

Diacylglycerol (DAG) has garnered attention for its safe and nutritious qualities, and its utilization in emulsion systems to encapsulate hydrophobic bioactives is anticipated to enhance their bioaccessibility. Thus, this study aimed to evaluate the influence of DAG oil as a carrier on the stability and digestive characteristics of nanostructured lipid carriers (NLCs) containing lycopene (LYC). The results indicated that DAG oil demonstrated superior storage and heating stability in comparison to triacylglycerol (TAG) oil. Furthermore, NLCs formulated with DAG oil exhibited a faster rate of lipolysis (>76.3%) and higher loading capacity (1.48%), resulting in an approximate 11% enhancement in the bioaccessibility of LYC (reaching up to 31.4%). DAG oils show considerable potential for enhancing and prolonging the properties and bioactivity of NLC carriers, thereby boosting bioaccessibility. The incorporation of DAG oil in food systems holds promise for enriching their functionality over traditional TAG oil.

Verapamil inhibits respiratory syncytial virus infection by regulating Ca2+ influx.

AIMS: The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism. MATERIALS AND METHODS: RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca2+ and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil. KEY FINDINGS: Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca2+ channels and inhibiting virus replication. SIGNIFICANCE: Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.

Supplementation with Combined Additive Improved the Production of Dairy Cows and Their Offspring with Maintenance of Antioxidative Stability.

Oxidative stress damage in periparturient cows decreases both production and their health; supplementation with complex additives during the periparturient period has been used as an important strategy to enhance the antioxidant status and production of dairy cows. The periparturient cows not only risk a negative energy balance due to reduced dry matter intake but also represent a sensitive period for oxidative stress. Therefore, we have developed an immunomodulatory and nutritional regulation combined additive (INC) that hopefully can improve the immune status and production of cows during the periparturient period and their offspring health and growth by improving their antioxidant stress status. The INC comprised a diverse array of additives, including water-soluble and fat-soluble vitamins, Selenomethionine, and active dry Saccharomyces cerevisiae. Forty-five multiparous Holstein cows were randomly assigned to three treatments: CON (no INC supplementation, n = 15), INC30 (30 g/d INC supplementation, n = 15), and INC60 (60 g/d INC supplementation, n = 15) based on last lactation milk yield, body condition score, and parity. Newborn calves were administered 4 L of maternal colostrum originating from the corresponding treatment and categorized based on the treatment received by their respective dams. The INC not only served to maintain the antioxidative stress system of dairy cows during the periparturient period but also showed a tendency to improve the immune response (lower tumor necrosis factor and interleukin-6) during the perinatal period. A linear decrease in concentrations of alkaline phosphatase postpartum and ß-hydroxybutyrate was observed with INC supplementation. Milk fat yield, milk protein yield, and energy-corrected milk yield were also increased linearly with increasing additive supplementation. Calves in the INC30 group exhibited greater wither height and chest girth but no significant effect on average daily gain or body weight. The diarrhea frequency was linearly decreased with the incremental level of INC. Results indicate that supplementation with INC in peripartum dairy cows could be a major strategy to improve immune response, decrease inflammation, maintain antioxidant stress status in transition dairy cows, and have merit in their calves. In conclusion, this study underlines the benefits of INC supplementation during the transition period, as it improved anti-inflammatory capacity, could positively impact antioxidative stress capacity, and eventually enhanced the production performance of dairy cows and the health and growth of calves.

[Radial growth response of Populus euphratica to climate change in the Cele desert oasis ecotone, China]. / ç­–å‹’æ²™æ¼ ç»¿æ´²è¿‡æ¸¡å¸¦èƒ¡æ¨å¾„å‘ç”Ÿé•¿å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

Populus euphratica is an important tree species in the arid regions of Northwest China, which is sensitive to climate changes. Climate of the Northwest China is changing to be "warm and humid", but how it would affect the regional forest growth is not clear. In this study, the radial growth response of P. euphratica to major climatic factors and their temporal changes during 1984-2021 were analyzed by using dendrochronology method in the desert oasis ecotone of Cele in the southern Tarim basin. The results showed that tree-ring width index of P. euphratica had a significant negative correlation with temperature in September of the previous year, and in February and May of current year, had significant positive correlation with precipitation in September of previous year and March and May of current year, and had significant positive correlations with SPEI in February and May of current year. The relationships between tree-ring width index and combined month climatic factors were more obvious. The results of moving correlation analysis showed that the correlation between tree-ring width index and temperature in the growing season tended to be strengthened in recent years, while the correlation between tree-ring width index and precipitation, SPEI tended to be declined or remain stable. The variations of the relationships between tree-ring width index and combined month climatic factors were more obvious compared that with single month. Current regional climate is conducive to the growth and development, as well as the improvement of ecological shelter function of P. euphratica forest in the desert oasis ecotone of Cele.

Report on three cases of familial primary aldosteronism type IV.

Primary aldosteronism is the most common cause of secondary hypertension, which is caused by increased aldosterone secretion in the adrenal cortex and contains many subtypes, among which familial hyperaldosteronism is relatively rare. Familial hyperaldosteronism can be divided into four subtypes based on its clinical manifestations and mutated genes: FH-I, FH-II, FH-III, and FH-IV. This article reports on three patients with FH-IV: a mother and her two sons. They were diagnosed with hypertension in other hospitals, and hypokalemia was found during hospitalization in our department. Diltiazem and terazosin were used for elution for 1 month. Renin and aldosterone levels in standing or supine positions improved, and the aldosterone-to-renin ratio was positive. Primary aldosteronism was diagnosed based on improved saline and captopril inhibition tests. As the three patients were blood-related immediate family members, gene screening was performed, diagnosing them with FH-IV. This article reports the clinical characteristics of the three cases in combination with related literature to improve the understanding of FH-IV.

The complete chloroplast genomes of Polygonatum hunanense, P. verticillatum, and P. caulialatum and their phylogenetic positions.

Polygonatum hunanense H.H. Liu & B.Z. Wang (2021) and P. verticillatum (L.) All. (1875) have been widely used as foods and as folk medicines in China and India, and P. caulialatum S. R. Yi (2021) has recently been described as a new medical plant in China. There is at present a lack of genome information regarding the species. Hence, this study reports the complete chloroplast genomes of the three species. The genomes of P. hunanense, P. verticillatum, and P. caulialatum were 155,583 bp, 155,650 bp, and 155,352 bp in length, respectively. They contained large single-copy (LSC) regions of 84,412 bp, 84,404 bp, and 84,285 bp, small single-copy (SSC) regions of 18,427 bp, 18,416 bp, and 18,463 bp, and a pair of inverted repeats of 26,372 bp, 26,415 bp, and 26,302 bp, respectively. The chloroplast genomes of P. hunanense, P. verticillatum, and P. caulialatum had 133 (103 unique) genes, consisting of 87 protein-coding genes, 38 ribosomal ribonucleic acid (RNA) genes, and eight transfer RNA genes, respectively. A maximum-likelihood phylogenetic tree showed that P. kingianum Coll. et Hemsl. var. grandifolium D.M. Liu & W.Z. Zeng (1991) was closer to P. cyrtonema Hua (1892) rather than to P. kingianum Coll. et Hemsl. (1890), further supporting its status as a unique species of the genus. Moreover, P. verticillatum was separated from the easily confused herb P. cirrhifolium (Wall.) Royle (1839), while P. caulialatum was closest to P. humile Fisch. ex Maxim. (1859). This research provides a foundation for further study of these herbs.

DNA nanoassembly based turn-on amplification probe for sensitive colorimetric CRISPR/Cas12a-mediated detection of pathogen DNA.

Clustered regularly interspaced short palindromic repeat (CRISPR) system has been explored as an efficient tool for nucleic acid diagnostics. However, it normally needs instrumentation or produces turn-off signals. Herein, a bulged Y-shape DNA (Y-DNA) nanoassembly was designed and synthesized as a novel turn-on probe. A CRISPR/Cas12a and Y-DNA probe mediated colorimetric assay (named as CYMCOA) strategy was developed for visual detection of pathogen DNA. Upon activating Cas12a with pathogen DNA, the Y-DNA bulge is catalytically trans-cleaved, releasing the G-quadruplex sequence embedded in the Y-DNA nanoassembly as a peroxidase-like DNAzyme. Visible signals with chromogen substrates are thus produced. The CYMCOA strategy was combined with recombinase polymerase amplification (RPA), an isothermal amplification technique, in detecting Helicobacter pylori (Hp) bacteria and SARS-CoV-2 N plasmids as two model pathogens. The bioassay has very excellent detection sensitivity and specificity, owing to the triple cascade amplification reactions and the very low mismatch tolerance. The lower limit of detection values were 0.16 cfu⋅mL-1, 1.5 copies⋅µL-1, and 0.17 copies⋅µL-1 for Hp bacteria, Hp plasmids, and SARS-CoV-2 N plasmids respectively. The detection is fast and accurate. The colorimetric bioassay strategy provides to be a simple, accurate, fast and instrumentation-free platform for nucleic acids detections in various settings, including crude and emergent situations.

3.73 W all-solid-state dual-wavelength Nd:Lu2O3 crystal laser.

The laser output characteristics of N d:L u 2 O 3 crystals were investigated in detail to obtain a dual-wavelength all-solid-state laser. Using 806 nm LD end-face pumped N d:L u 2 O 3 crystals with lengths of 6 mm, a 1076 & 1080 nm laser outputs with a maximum output power of 3.73 W were obtained, with a slope efficiency of 30.4%, an optical-to-optical conversion efficiency of 28.5%, and a power stability of 0.41% for 4 h of continuous measurement. Furthermore, by suppressing the higher-order modes, a high beam quality laser output with beam quality factors of 2.092 and 1.589 in the x and y directions, respectively, and a maximum output power of 1.27 W were obtained. In addition, it was experimentally verified that both wavelengths of the output laser were elliptically polarized.

Influence of meaningfulness of work and leadership characteristics on customer-directed counterproductive work behavior resulting from customer mistreatment.

This study explored the impact of customer mistreatment on counterproductive work behavior (CWB) and the moderating role of supervisor responses (self-sacrificial and self-serving leadership) to clarify why customer-directed CWB occurs and how it can be reduced. A sample of 392 customer-facing employees in the USA completed measures assessing the meaningfulness of work and self-sacrificial and self-serving leadership experiences. The meaningfulness of work moderated the relationship between customer mistreatment and employee anger, and a three-way interaction was found between employee anger and self-sacrificial and self-serving leadership on customer-directed CWB. Implications for managing customer mistreatment and fostering meaningful work to promote employee well-being are discussed.

Activin A, a Novel Chemokine, Induces Mouse NK Cell Migration via AKT and Calcium Signaling.

Natural killer (NK) cells can migrate quickly to the tumor site to exert cytotoxic effects on tumors, and some chemokines, including CXCL8, CXCL10 or and CXCL12, can regulate the migration of NK cells. Activin A, a member of the transforming growth factor ß (TGF-ß) superfamily, is highly expressed in tumor tissues and involved in tumor development and immune cell activation. In this study, we focus on the effects of activin A on NK cell migration. In vitro, activin A induced NK cell migration and invasion, promoted cell polarization and inhibited cell adhesion. Moreover, activin A increased Ca2+, p-SMAD3 and p-AKT levels in NK cells. An AKT inhibitor and Ca2+ chelator partially blocked activin A-induced NK cell migration. In vivo, exogenous activin A increased tumor-infiltrating NK cells in NS-1 cell solid tumors and inhibited tumor growth, and blocking endogenous activin A with anti-activin A antibody reduced tumor-infiltrating NK cells in 4T-1 cell solid tumors. These results suggest that activin A induces NK cell migration through AKT signaling and calcium signaling and may enhance the antitumor effect of NK cells by increasing tumor-infiltrating NK cells.

Optimization and mechanisms of proteolytic enzyme immobilization onto large-pore mesoporous silica nanoparticles: Enhanced tumor penetration.

Immobilization of proteolytic enzymes onto nanocarriers is effective to improve drug diffusion in tumors through degrading the dense extracellular matrix (ECM). Herein, immobilization and release behaviors of hyaluronidase, bromelain, and collagenase (Coll) on mesoporous silica nanoparticles (MSNs) were explored. A series of cationic MSNs (CMSNs) with large and adjustable pore sizes were synthesized, and investigated together with two anionic MSNs of different pore sizes. CMSNs4.0 exhibited the highest enzyme loading capacity for hyaluronidase and bromelain, and CMSNs4.5 was the best for Coll. High electrostatic interaction, matched pore size, and large pore volume and surface area favor the immobilization. Changes of the enzyme conformations and surface charges with pH, existence of a space around the immobilized enzymes, and the depth of the pore structures, affect the release ratio and tunability. The optimal CMSNs-enzyme complexes exhibited deep and homogeneous penetration into pancreatic tumors, a tumor model with the densest ECM, with CMSNs4.5-Coll as the best. Upon loading with doxorubicin (DOX), the CMSNs-enzyme complexes induced high anti-tumor efficiencies. Conceivably, the DOX/CMSNs4.5-NH2-Coll nanodrug exhibited the most effective tumor therapy, with a tumor growth inhibition ratio of 86.1 %. The study provides excellent nanocarrier-enzyme complexes, and offers instructive theories for enhanced tumor penetration and therapy.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

circMIRIAF aggravates myocardial ischemia-reperfusion injury via targeting miR-544/WDR12 axis.

Exploring and discovering novel circRNAs is one of the ways to develop innovative drugs for the diagnosis and treatment of myocardial ischemia-reperfusion injury (MI/RI). In the work, some dysregulated circRNAs were found by microarray screening analysis in AC16 cells, and hsa_circRNA_104852 named circMIRIAF was screened, which was up-regulated in AC16 cells damaged by hypoxia-reoxygenation injury (H/RI). The comprehensive analysis of ceRNA network revealed the potential relationship of circMIRIAF/miR-544/WDR12. Then, the results of interaction research confirmed that circMIRIAF acted as sponge of miR-544 to positively regulate WDR12 protein expression. Further, the validation results indicate that miR-544 silencing increased the expression of WDR12, and WDR12 activated Notch1 signal to aggravate H/RI of AC16 cells and MI/RI of mice via regulating oxidative stress and inflammation. Furthermore, silencing circMIRIAF caused the decreased circMIRIAF levels and the increased miR-544 levels in cardiomyocytes, while excessive miR-544 inhibited WDR12 expression to alleviate the disorder. On the contrary, excessive circMIRIAF increased WDR12 expression by adsorbing miR-544 to exacerbate H/RI in AC16 cells. In addition, circMIRIAF siRNA reversed the aggravation of H/RI in cells caused by WDR12 overexpression. Overall, circMIRIAF can serve as a drug target or treating MI/RI, and circMIRIAF could sponge miR-544 and enhance WDR12 expression to aggravate MI/RI, which may provide a novel therapeutic strategy for MI/RI treatment.

Design of ultrahigh-Q silicon microring resonators based on free-form curves.

A design method for ultrahigh-Q microring resonators (MRRs) based on Bezier free-form curves was proposed and demonstrated. An MRR consisting of a specially designed 180° waveguide bend, a directional coupler, and two low-loss multi-mode strip waveguides was designed. The free-form curves were used to increase the degree of freedom in the design, shaping the waveguide bend with a gradient width and curvature. This design effectively reduced the propagation loss caused by the roughness of waveguide sidewalls and the mode mismatch loss caused by the excitation of high order modes. The small effective radius of only 20µm enabled the MRR to have a large free spectral range (FSR) and a compact and flexible structure. The MRR was manufactured using a standard process provided by foundry and measured to have an ultrahigh loaded Q factor of 1.86 × 106 and a FSR of about 1 nm.

Temporomandibular disorder symptoms and their association with quality of life of dental patients in Malaysia.

OBJECTIVE: To assess the prevalence of temporomandibular disorders (TMD) and their effects on quality of life (QoL) of dental patients. METHODS: A survey consisting of two validated questionnaires was distributed to dental patients registered at the University of Malaya Faculty of Dentistry. The Fonseca Anamnestic Index (FAI) evaluates the prevalence and severity of TMD, while the Oral Health Impact Profile - Temporomandibular Disorder (OHIP-TMD) appraises the effects of TMD on oral health-related QoL. RESULTS: Out of 342 patients (aged 16 to 50 years, 45% male and 55% female) enrolled in the survey, 50.9% had varying degrees of TMD. All 7 domains of OHIP-TMD showed a statistically significant correlation with TMD severity. CONCLUSION: TMD seems to be prevalent among Malaysian dental patients. Not only does TMD affect the QoL of an individual, but the more severe the degree of reported symptoms, the poorer their perceived oral health QoL.

Neolignans with anti-inflammatory activity from Piper kadsura (Choisy) Ohwi.

Two novel neolignans, piperkadsurenin A (1) and kadsurenin N (2), along with six known neolignans (3-8) and two lignans (9-10) were isolated from the stems of Piper kadsura (Choisy) Ohwi. Extensive spectroscopic data interpretation and ECD calculations were used to identify the structures of the new compounds 1 and 2. Especially, compound 1 represents the first example of neolignan with cyclopenta[b]pyran framework. The anti-inflammatory efficacy of compounds 1-10 in vitro was systematically assessed through NO production inhibitory assay. Compounds 3 and 7 significantly inhibited LPS-induced NO generation in RAW 264.7 cells, with IC50 values of 34.29 ± 0.82 and 47.5 ± 5.81 µM, respectively.

Soybean steroids improve crop abiotic stress tolerance and increase yield.

Sterols have long been associated with diverse fields, such as cancer treatment, drug development, and plant growth; however, their underlying mechanisms and functions remain enigmatic. Here, we unveil a critical role played by a GmNF-YC9-mediated CCAAT-box transcription complex in modulating the steroid metabolism pathway within soybeans. Specifically, this complex directly activates squalene monooxygenase (GmSQE1), which is a rate-limiting enzyme in steroid synthesis. Our findings demonstrate that overexpression of either GmNF-YC9 or GmSQE1 significantly enhances soybean stress tolerance, while the inhibition of SQE weakens this tolerance. Field experiments conducted over two seasons further reveal increased yields per plant in both GmNF-YC9 and GmSQE1 overexpressing plants under drought stress conditions. This enhanced stress tolerance is attributed to the reduction of abiotic stress-induced cell oxidative damage. Transcriptome and metabolome analyses shed light on the upregulation of multiple sterol compounds, including fucosterol and soyasaponin II, in GmNF-YC9 and GmSQE1 overexpressing soybean plants under stress conditions. Intriguingly, the application of soybean steroids, including fucosterol and soyasaponin II, significantly improves drought tolerance in soybean, wheat, foxtail millet, and maize. These findings underscore the pivotal role of soybean steroids in countering oxidative stress in plants and offer a new research strategy for enhancing crop stress tolerance and quality from gene regulation to chemical intervention.

Evaluating the link between DIO3-FA27 promoter methylation, biochemical indices, and heart failure progression.

BACKGROUND: Heart failure (HF) is a disease that poses a serious threat to individual health, and DNA methylation is an important mechanism in epigenetics, and its role in the occurrence and development of the disease has attracted more and more attention. The aim of this study was to evaluate the link between iodothyronine deiodinase 3 promoter region fragment FA27 (DIO3-FA27) methylation levels, biochemical indices, and HF. RESULTS: The methylation levels of DIO3-FA27_CpG_11.12 and DIO3-FA27_CpG_23.24 significantly differed in HF patients with different degrees. Multivariate logistic regression analysis indicated that the relative HF risk in the third and fourth quartiles of activated partial thromboplastin time and fibrin degradation products. The results of the restricted cubic spline model showed that the methylation levels of DIO3-FA 27_CpG_11.12 and DIO3-FA 27_CpG_23.24 were associated with coagulation indicators, liver function, renal function, and blood routine. CONCLUSIONS: Based on the differential analysis of CpG methylation levels based on DIO3-FA27, it was found that biochemical indicators combined with DIO3-FA27 promoter DNA methylation levels could increase the risk of worsening the severity classification of HF patients, which provided a solid foundation and new insights for the study of epigenetic regulation mechanisms in patients with HF.