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The article discusses the potential for targeting systemic inflammation in patients with heart failure through leucocyte immunomodulation. It highlights the high incidence of cardiovascular mortality and hospitalizations for heart failure despite current therapies. The role of inflammation in heart failure is explored, with a focus on the involvement of proinflammatory cytokines and biomarkers. The article introduces a novel approach using a selective cytopheretic device (SCD) to target activated neutrophils and monocytes, which has shown promise in reducing systemic inflammation and improving outcomes in other acute conditions. A case report is presented to demonstrate the potential effectiveness of the SCD in bridging patients to left ventricular assist device (LVAD) implantation. The article concludes by suggesting that further studies are needed to evaluate the use of the SCD and its potential to reduce cardiovascular mortality and hospitalizations in heart failure patients. [Extracted from the article]

Background: Selective depletion of T cells expressing LAG-3, an immune checkpoint receptor that is upregulated on activated T cells, has been investigated in pre-clinical models as a potential therapeutic approach in inflammatory and autoimmune diseases where activated T cells are implicated., Aims: GSK2831781, a depleting monoclonal antibody that specifically binds LAG-3 proteins, may deplete activated LAG-3 + cells in ulcerative colitis (UC)., Methods: Patients with moderate to severe UC were randomised to GSK2831781 or placebo. Safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of GSK2831781 were evaluated., Results: One hundred four participants across all dose levels were randomised prior to an interim analysis indicating efficacy futility criteria had been met. Efficacy results focus on the double-blind induction phase of the study (GSK2831781 450 mg intravenously [IV], N = 48; placebo, N = 27). Median change from baseline (95% credible interval [CrI]) in complete Mayo score was similar between groups (GSK2831781 450 mg IV: -1.4 [-2.2, -0.7]; placebo: -1.4 [-2.4, -0.5]). Response rates for endoscopic improvement favoured placebo. Clinical remission rates were similar between groups. In the 450-mg IV group, 14 (29%) participants had an adverse event of UC versus 1 (4%) with placebo. LAG-3 + cells were depleted to 51% of baseline in blood; however, there was no reduction in LAG-3 + cells in the colonic mucosa. Transcriptomic analysis of colon biopsies showed no difference between groups., Conclusion: Despite evidence of target cell depletion in blood, GSK2831781 failed to reduce inflammation in the colonic mucosa suggesting no pharmacological effect. The study was terminated early (NCT03893565)., (© 2023 GSK and The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Currently described hyperkalemia (HK) animal models are typically acute and cause significant distress and mortality to the animals, warranting new approaches for studying chronic HK in a more appropriate clinical setting. Using the spontaneously hypertensive rat (SHR) model as a more relevant disease template, as well as surgical (unilateral nephrectomy), dietary (3% potassium [K+] supplementation), and pharmacological (amiloride) interventions, we were able to stably induce HK on a chronic basis for up to 12 weeks to serum K+ elevations between 8 and 9 mmol/L, with minimal clinical stress to the animals. Short‐term proof‐of‐concept and long‐term chronic studies in hyperkalemic SHRs showed concomitant increases in serum aldosterone, consistent with the previously reported relationship between serum K+ and aldosterone. Treatment with the K+ binder patiromer demonstrated that the disease model was responsive to pharmacological intervention, with significant abrogation in serum K+, as well as serum aldosterone to levels near baseline, and this was consistent in both short‐term and long‐term 12‐week chronic studies. Our results demonstrate the feasibility of establishing a chronic HK disease state, and this novel HK animal model may be suitable for further evaluating the effects of long‐term, K+‐lowering therapies on effects such as renal fibrosis and end‐organ damage. [ABSTRACT FROM AUTHOR]

1. Despite considerable theoretical work, the evolution of population stability has rarely been investigated empirically. Moreover, it is not clear whether different stability properties of a population evolve together, or independently. 2. We investigate the evolution of two aspects of population stability using laboratory populations of Drosophila melanogaster selected for faster preadult development and early reproduction, and their matched controls. 3. We show that the constancy stability of the selected populations is significantly higher than their controls, confirming a previous observation that population stability can evolve as a by-product of life-history evolution. This enhanced constancy stability is due to a reduced maximal per capita growth rate, brought about by a reduction in fecundity of the selected populations as a result of the trade-off between developmental rate and fecundity. 4. Persistence stability, as reflected by the probability of extinction, does not differ significantly between selected and control populations. 5. We also show how seemingly trivial experimental details, such as the protocol for restarting extinct populations, can interact with life-history traits to alter the manifestation of the stability properties of a population. [ABSTRACT FROM AUTHOR]

The crystallization kinetics in the glass system (100-x) LiBO2-xNb2O5 (5≤x≤20, in molar ratio) prepared via the conventional metal-plate quenching technique have been studied by isothermal and non-isothermal methods using differential thermal analysis. X-ray powder diffraction studies carried out on heat-treated (500°C) glasses reveal the evolution of lithium niobate crystalline phase along with a minor phase of LiBO2. The exponent n in the Jhonson-Mehl-Avrami (JMA) equation applied to the isothermal process is 2.62, which is in excellent agreement with that obtained under the non-isothermal process (2.67). The activation energies for crystal growth obtained from JMA equation under isothermal condition, modified Ozawa and Kissinger equations under non-isothermal conditions, are 293, 311, and 306 kJ/mol, respectively. [ABSTRACT FROM AUTHOR]

Les grandes enquětes gouvernementales permettent généralement de produire des statistiques précises au plan national. Pour décroǐtre l'erreur quadratique moyenne des estimations pour les petites régions, c'est-à-dire les secteurs pour lesquels la taille d'échantillon est faible, on a souvent recours à des variables auxiliaires extraites de fichiers administratifs, lesquelles servent de covariables dans un modèle linéaire mixte. On suppose d'habitude que cette information auxiliaire est disponible pour toutes les petites régions. Dans plusieurs cas, toutefois, on ne dispose de tels renseignements que pour certaines d'entre elles, soit par l'intermédiaire d'une autre enquěte ou d'une édition précédente de la měme enquěte. Les auteurs proposent et étudient des estimateurs pour petites régions qui font appel à des modèles multivariés permettant de combiner les données provenant de plusieurs enquětes. Ils présentent des algorithmes de calcul et font état d'une étude de simulation montrant que si les variables des différentes enquětes sont suffisamment corrélées, de substantiels gains d'efficacité sont possibles. [ABSTRACT FROM AUTHOR]

The bacterial transposon Tn7 utilizes four Tn7-encoded proteins, TnsA, TnsB, TnsC and TnsD, to make insertions at a specific site termed attTn7. This target is selected by the binding of TnsD to attTn7 in a sequence-specific manner, followed by the binding of TnsC and activation of the transposase. We show that TnsD binding to attTn7 induces a distortion at the 5' end of the binding site and TnsC contacts the region of attTn7 distorted by TnsD. Previous work has shown that a target site containing triplex DNA, instead of TnsD-attTn7, can recruit TnsABC and effect sitespecific insertion of Tn7. We propose that the DNA distortion imposed by TnsD on attTn7, like the altered DNA structure via triplex formation, serves as a signal to recruit TnsC. We also show that TnsD primarily contacts the major groove of DNA, whereas TnsC is a minor groove binding protein. The footprint of the TnsC-TnsD-attTn7 nucleoprotein complex includes and extends beyond the Tn7 insertion site, where TnsC forms a platform to receive and activate the transposase to carry out recombination. [ABSTRACT FROM AUTHOR]

In present research the fracture behavior of carbon fabric‐epoxy composites (CE composites) was evaluated with the addition of 0.1, 0.2, 0.5, and 0.75 weight percentages of carbon nano tubes (CNTs) at different temperatures. The CE composites with different wt.% of CNT were fabricated using land layup method and cured by hot pressing. The fracture toughness of fabricated composites was evaluated in mode–I condition at different temperature. From the results it was shown that the highest fracture toughness was observed at 0.75 wt.% of reinforcement of CNT functional fillers. The fracture toughness of 0.75 wt.% CNT filled CE composites was increased by 19.73% compared to unfilled CE composites. The fracture toughness of CNT filled CE composites diminishes with increase in temperature and the composite filled with 0.75 wt.% CNT exhibits better fracture toughness than the unfilled CE composite at all the temperatures. The fracture toughness was improved by 57.76% and 71.65% at 40 and 60°C, respectively, at 0.75 wt.% reinforcement of CNT fillers. The fractured surfaces of composites were analyzed using Scanning Electron Microscope (SEM) to study the filler contribution to enhance the fracture toughness and failure mechanism of composites. [ABSTRACT FROM AUTHOR]

Aims: Chronic systolic heart failure (CHF) is a major health burden. A relevant number of patients shows asymptomatic left ventricular dysfunction (ALVSD) before symptomatic CHF or becomes asymptomatic after initiating heart failure therapy. Clinical course, prognosis, and response to pharmacological and device‐based treatment are largely unknown in these two distinct groups of patients. Current pharmacological and interventional therapies do neither properly address the underlying pathophysiology nor prevent malignant loss of function. New therapeutic paradigms are needed to stop the progression from asymptomatic to symptomatic heart failure. Key questions are what causes progression of clinically asymptomatic New York Heart Association (NYHA) I heart failure to overt heart failure (>NYHA I) in some but not all patients and the underlying reasons for this transition. This requires the identification of disease mechanisms and biomarkers that predict outcome in well‐defined cohorts for innovative preclinical and clinical trials. Methods and results: TransitionCHF is a prospective, multicentre, longitudinal pathophysiological evaluation cohort study in patients with asymptomatic systolic dysfunction NYHA I and left ventricular ejection fraction ≤40%. The cohort comprises both incidental findings and patients who had become asymptomatic after a previous symptomatic event. TransitionCHF has recruited 1000 patients with ALVSD caused by various aetiologies in 20 university heart failure clinics across Germany. Both patients with and without comorbidities at study entry will be recruited. Patients will be systematically investigated and followed up annually over the course of the study. The primary composite endpoint is time to hospitalization for heart failure and cardiovascular death. The secondary endpoints assess time to all‐cause mortality, to cardiovascular mortality, to heart failure mortality, to all‐cause hospitalization, to heart failure hospitalization, and to recurrent heart failure hospitalizations, as well as time to assist device implantation/transplantation. Additional investigations focusing on biomarkers, comorbidities, gender aspects, nutrition, and functional parameters including quality of life will be performed. Conclusions: TransitionCHF will provide a more thorough pathophysiological understanding of the progression of asymptomatic systolic dysfunction into symptomatic heart failure that will help develop therapies tailored to prevent progressive heart failure. [ABSTRACT FROM AUTHOR]

Background: Social media has fostered a landscape where trends, ideals, and beauty standards have significantly proliferated. Images of flawless skin, sculpted features, and curated aesthetics inundate user feeds, potentially shaping their self‐perceptions and aspirations. The rise of influencers, dermatologist social media engagement, and beauty campaigns sharing skincare routines and product recommendations wield substantial influence over individual appearance‐related decisions. Aims: The main aim of this study is to determine the pattern of behavior in using social media to seek dermatological procedures and skin care routine. Methods: We conducted a nationwide, online cross‐sectional study targeting the general Saudi population. Our survey aimed to understand participant social media behaviors and gather insights into skincare products, cosmetic procedures, and makeup habits. Results: Gender‐related differences emerged in seeking skincare advice. Females preferred dermatologists on social media (p < 0.001) and beauty influencers (p < 0.001), whereas men leaned towards pharmacists (p < 0.001). Women displayed stronger engagement with dermatologist social media reputation regarding non‐cosmetic concerns (p < 0.001), education (p < 0.001), and social media impact on cosmetic decisions (p = 0.001). They frequently sought dermatologists on social media before appointments (p = 0.001), whereas men emphasized dermatologists' fame (p = 0.024). Common cosmetic barriers included high costs (62.5%), complications (40.3%), and trust issues (40.2%). Women underwent various cosmetic procedures (p < 0.05), influenced by social media in their decisions and skincare routines. Conclusions: Our study reveals significant gender‐based disparities in seeking skincare advice. Women rely on social media, clinics, friends, and beauty influencers, whereas men prefer pharmacists. Additionally, women depend on dermatologists' social media reputation and conduct thorough pre‐appointment research. Their heightened social media engagement links to skincare practices and influences cosmetic procedure considerations based on age and usage frequency. [ABSTRACT FROM AUTHOR]

Currently, the concentration of carbon dioxide (CO2) has exceeded 400 ppm in the atmosphere. Thus, there is an urgent need to explore CO2 reduction and utilization technologies. Photocatalytic technology can convert CO2 to valuable hydrocarbons (CH4, CH3OH, and C2H5OH, etc.), realizing the conversion of solar energy to chemical energy as well as solving the problems of fossil fuel shortage and global warming. Graphitic carbon nitride (g‐C3N4), as a two‐dimensional nonmetallic semiconductor material, shows great potential in the field of CO2 photoreduction due to its moderate bandgap, easy synthesis method, low cost, and visible light response properties. This review elaborates the research progress of g‐C3N4‐based photocatalysts for photocatalytic CO2 reduction. The modification strategies (e.g., morphology engineering, elemental doping, crystallinity modulation, cocatalyst modification, and constructing heterojunction) of g‐C3N4‐based photocatalysts for CO2 reduction application have been discussed in detail. Finally, the challenges and development prospects of g‐C3N4‐based photocatalytic materials for CO2 reduction are presented. [ABSTRACT FROM AUTHOR]

Heart failure (HF), with its high morbidity and mortality, remains a global public health issue. Right ventricular (RV) dysfunction is a sign of deterioration in the natural history of HF, and a thorough evaluation of the relationship between RV contractility and its afterload through RV–pulmonary arterial (RV–PA) coupling can aid in accurately assessing overall RV function. The ratio of RV end‐systolic elastance (Ees) to pulmonary arterial elastance (Ea) invasively measured by right heart catheterization served as the gold standard for evaluating RV–PA coupling. An echocardiographic index termed tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) has been shown to correlate well with Ees/Ea. TAPSE/PASP is recognized as a non‐invasive surrogate of RV–PA coupling and has been extensively studied in patients with HF. This review briefly describes the methods of assessing RV–PA coupling, mainly discussing echocardiography, summarizes the clinical utility of TAPSE/PASP in patients with different HF types, and provides an overview of the available literature. [ABSTRACT FROM AUTHOR]

Background: DNA repair mechanisms are essential for tumorigenesis and disruption of HR mechanism is an important predisposing factor of human breast cancers (BC). PALB2 is an important part of the HR. There are similarities between canine mammary tumours (CMT) and BCs. As its human counterpart, PALB2 mutations could be a predisposing factor of CMT. Objectives: In this study, we aimed to investigate the impacts of PALB2 variants on tumorigenesis and canine mammary tumor (CMT) malignancy. Methods: We performed Sanger sequencing to detect germline mutations in the WD40 domain of the canine PALB2 gene in CMT patients. We conducted in silico analysis to investigate the variants, and compared the germline PALB2 mutations in humans that cause breast cancer (BC) with the variants detected in dogs with CMT. Results: We identified an intronic (c.3096+8C>G) variant, two exonic (p.A1050V and p.R1354R) variants, and a 3′ UTR variant (c.4071T>C). Of these, p.R1354R and c.4071T>C novel variants were identified for the first time in this study. We found that the p.A1050V mutation had a significant effect. However, we could not determine sufficient similarity due to the differences in nucleotide/amino acid sequences between two species. Nonetheless, possible variants of human sequences in the exact location as their dog counterparts are associated with several cancer types, implying that the variants could be crucial for tumorigenesis in dogs. Our results did not show any effect of the variants on tumor malignancy. Conclusions: The current project is the first study investigating the relationship between the PALB2 gene WD40 domain and CMTs. Our findings will contribute to a better understanding of the pathogenic mechanism of the PALB2 gene in CMTs. In humans, variant positions in canines have been linked to cancer‐related phenotypes such as familial BC, endometrial tumor, and hereditary cancer predisposition syndrome. The results of bioinformatics analyses should be investigated through functional tests or case‐control studies. [ABSTRACT FROM AUTHOR]

Aging exhibits several hallmarks in common with cancer, such as cellular senescence, dysbiosis, inflammation, genomic instability, and epigenetic changes. In recent decades, research into the role of cellular senescence on tumor progression has received widespread attention. While how senescence limits the course of cancer is well established, senescence has also been found to promote certain malignant phenotypes. The tumor‐promoting effect of senescence is mainly elicited by a senescence‐associated secretory phenotype, which facilitates the interaction of senescent tumor cells with their surroundings. Targeting senescent cells therefore offers a promising technique for cancer therapy. Drugs that pharmacologically restore the normal function of senescent cells or eliminate them would assist in reestablishing homeostasis of cell signaling. Here, we describe cell senescence, its occurrence, phenotype, and impact on tumor biology. A "one‐two‐punch" therapeutic strategy in which cancer cell senescence is first induced, followed by the use of senotherapeutics for eliminating the senescent cells is introduced. The advances in the application of senotherapeutics for targeting senescent cells to assist cancer treatment are outlined, with an emphasis on drug categories, and the strategies for their screening, design, and efficient targeting. This work will foster a thorough comprehension and encourage additional research within this field. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a lethal gynecologic cancer mostly diagnosed in an advanced stage with an accumulation of ascites. Interleukin‐6 (IL‐6), a pro‐inflammatory cytokine is highly elevated in malignant ascites and plays a pleiotropic role in cancer progression. Mitochondria are dynamic organelles that undergo fission and fusion in response to external stimuli and dysregulation in their dynamics has been implicated in cancer progression and metastasis. Here, we investigate the effect of IL‐6 on mitochondrial dynamics in ovarian cancer cells (OVCs) and its impact on metastatic potential. Treatment with IL‐6 on ovarian cancer cell lines (SKOV3 and PA‐1) led to an elevation in the metastatic potential of OVCs. Interestingly, a positive association was observed between dynamin‐related protein 1 (Drp1), a regulator of mitochondrial fission, and IL‐6R in metastatic ovarian cancer tissues. Additionally, IL‐6 treatment on OVCs was linked to the activation of Drp1, with a notable increase in the ratio of the inhibitory form p‐Drp1(S637) to the active form p‐Drp1(S616), indicating enhanced mitochondrial fission. Moreover, IL‐6 treatment triggered the activation of ERK1/2, and inhibiting ERK1/2 mitigated IL‐6‐induced mitochondrial fission. Suppressing mitochondrial fission through siRNA transfection and a pharmacological inhibitor reduced the IL‐6‐induced migration and invasion of OVCs. This was further supported by 3D invasion assays using patient‐derived spheroids. Altogether, our study suggests the role of mitochondrial fission in the metastatic potential of OVCs induced by IL‐6. The inhibition of mitochondrial fission could be a potential therapeutic approach to suppress the metastasis of ovarian cancer. [ABSTRACT FROM AUTHOR]

While mortality is often the primary focus of pathogen virulence, non‐lethal consequences, particularly for male reproductive fitness, are less understood; however, they are essential for understanding how sexual selection contributes to promoting resistance. We investigated how the fungal pathogen Metarhizium brunneum affects mating ability, fertility, and seminal fluid protein (SFP) expression of male Drosophila melanogaster paired with highly receptive virgin females in non‐competitive settings. Depending on sex and dose, there was a 3–6‐day incubation period after infection, followed by an abrupt onset of mortality. Meanwhile, the immune response was strongly induced already 38 h after infection and continued to increase as infection progressed. Latency to mate somewhat increased during the incubation period compared to sham‐treated males, but even on Day 5 post infection >90% of infected males mated within 2 h. During the incubation period, M. brunneum infection reduced male reproductive potential (the number of offspring sired without mate limitation) by 11%, with no clear increase over time. Approaching the end of the incubation period, infected males had lower ability to convert number of mating opportunities into number of offspring. After repeated mating, infected males had lower SFP expression than sham controls, more so in males that mated with few mates 24 h earlier. Overall, despite strong activation of the immune response, males' mating ability and fertility remained surprisingly little affected by the fungal infection, even shortly before the onset of mortality. This suggests that the selection for resistance acts mainly through mortality, and the scope for fertility selection to enhance resistance in non‐competing settings is rather limited. [ABSTRACT FROM AUTHOR]

We report the synthesis of tungsten sulfide (WS2) films using RF‐magnetron sputtering at different RF powers. X‐ray diffraction (XRD) data confirm the hexagonal crystal structure of WS2 with an average crystallite size of ∼44.54 Å. With increased RF power, the preferred orientation of WS2 crystallites shifts from (002) to (100). Linear sweep voltammetry (LSV) was used to assess the Photoelectrochemical (PEC) activity of WS2 films. The film deposited at 150 W demonstrated the highest photocurrent density of 5.44 mA/cm2. The 150 W film also showed a lower Tafel slope of ∼0.374 V/decade, indicating superior PEC activity. Mott Schottky's (MS) analysis revealed a notable shift in the flat band potential towards the negative side, suggesting a shifting of the Fermi level towards the conduction band. WS2 film grown at 150 W demonstrated a majority charge carrier density of 6.2×1021 cm−3 and a depletion layer width of 1.54 nm. The observed low charge transfer resistance of 155 Ω contributed to the enhanced PEC activity with a relaxation time constant of 37 ms. These properties suggest that WS2 can be suitable for PEC water splitting. [ABSTRACT FROM AUTHOR]

Objective: Many studies reported that tranexamic acid (TXA) was effective in reducing surgical blood loss in the perioperative period of medial open wedge high tibial osteotomy (MOWHTO). However, few studies focused on the simple topical use of TXA in MOWHTO, and the modality and dosage of topical use of TXA varied. The purpose of this study was to observe the effect of topical use of low‐dose TXA on drainage volume after MOWHTO, and to analyze the related influencing factors. Methods: Data of patients who underwent MOWHTO combined with arthroscopic knee surgery in our department from January 2019 to September 2021 were retrospectively analyzed. A total of 105 patients (38 males and 67 females, aged 57.7 ± 7.5 years) were included in this study who received topical TXA or no TXA. The patients were divided into three groups: control group (39 cases), 0.5 g TXA group (40 cases), 1 g TXA group (26 cases). Postoperative drainage volume, wound healing, incidence of hematoma and deep venous thrombosis (DVT) were observed and analyzed in the three groups. The effects of gender, hypertension and diabetes on postoperative drainage volume were analyzed using a t‐test. The correlation between age, body mass index (BMI), osteotomy gap and postoperative drainage volume were analyzed using the Pearson correlation coefficient. Results: The average postoperative drainage volume of the control group was 259.54 ± 226.33 mL, that of the 0.5 g TXA group was 277.18 ± 177.68 mL, and that of the 1 g TXA group was 229.15 ± 219.93 mL. There was no statistically significant difference in postoperative drainage volume among the three groups (F = 0.423, p = 0.656). There was no local hematoma and wound infection in the three groups. The wound fat liquefaction was found in one patient of the control group. The incidence of DVT was 38.9% (7/18) and 57.1% (8/14) in the control group and 0.5 TXA group, respectively. There was no significant difference in the incidence of DVT between the above two groups (p = 0.476). The average postoperative drainage volume of male patients in the three groups was higher than that of female patients, and the differences were statistically significant (p < 0.05). There was no correlation between age, BMI, osteotomy gap and postoperative drainage volume in the three groups (p > 0.05). Conclusion: Topical use of low‐dose TXA has no significant effect on drainage volume after MOWHTO. The drainage volume after MOWHTO in male patients was more than that in female patients. Topical administration of low‐dose TXA does not increase postoperative complications, such as DVT and hematoma. [ABSTRACT FROM AUTHOR]

At present, diabetes mellitus (DM) has been one of the most endangering healthy diseases. Current therapies contain controlling high blood sugar, reducing risk factors like obesity, hypertension, and so on; however, DM patients inevitably and eventually progress into different types of diabetes complications, resulting in poor quality of life. Unfortunately, the clear etiology and pathogenesis of diabetes complications have not been elucidated owing to intricate whole‐body systems. The immune system was responsible to regulate homeostasis by triggering or resolving inflammatory response, indicating it may be necessary to diabetes complications. In fact, previous studies have been shown inflammation plays multifunctional roles in the pathogenesis of diabetes complications and is attracting attention to be the meaningful therapeutic strategy. To this end, this review systematically concluded the current studies over the relationships of susceptible diabetes complications (e.g., diabetic cardiomyopathy, diabetic retinopathy, diabetic peripheral neuropathy, and diabetic nephropathy) and inflammation, ranging from immune cell response, cytokines interaction to pathomechanism of organ injury. Besides, we also summarized various therapeutic strategies to improve diabetes complications by target inflammation from special remedies to conventional lifestyle changes. This review will offer a panoramic insight into the mechanisms of diabetes complications from an inflammatory perspective and also discuss contemporary clinical interventions. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) contain a plethora of biomolecules, including nucleic acids, with diverse diagnostic and therapeutic application potential. Although reverse transcription‐quantitative PCR (RT‐qPCR) is the most widely applied laboratory technique to evaluate gene expression, its applicability in EV research is challenged by the lack of universal and stably present reference genes (RGs). In this study, we identify, validate and establish SNRPG, OST4, TOMM7 and NOP10 as RGs for the normalization of EV‐associated genes by RT‐qPCR. We show the stable presence of SNRPG, OST4, TOMM7 and NOP10 in multiple cell lines and their secreted EVs (n = 12) under different (patho)physiological conditions as well as in human‐derived biofluids (n = 3). Enzymatic treatments confirm the presence of SNRPG, OST4, TOMM7 and NOP10 inside EVs. In addition, the four EV‐associated RGs are stably detected in a size‐range of EV subpopulations. RefFinder analysis reveals that SNRPG, OST4, TOMM7 and NOP10 are more stable compared to RGs established specifically for cultured cells or tissues such as HMBS, YWHAZ, SDHA and GAPDH. In summary, we present four universal and stably present EV‐associated RGs to enable normalization and thus steer the implementation of RT‐qPCR for the analysis of EV‐associated RNA cargo for research or clinical applications. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have been proposed to play dual roles in cellular homeostasis, functioning both to remove unwanted intracellular molecules, and to enable communication between cells as a means of modulating cellular responses in different physiological and pathological scenarios. EVs contain a broad range of cargoes, including multiple biotypes of RNA, which can vary depending on the cell status, and may function as signalling molecules. In this study, we carried out comparative transcriptomic analysis of Drosophila EVs and cells, demonstrating that the RNAprofile of EVs is distinct from cells and shows dose-dependent changes in response to oxidative stress. We identified a high abundance of snoRNAs in EVs, alongside an enrichment of intronic and untranslated regions (UTRs) of mRNAs under stress. We also observed an increase in the relative abundance of either aberrant or modified mRNAs under stress. These findings suggest that EVsmay function both for the elimination of specific cellular RNAs, and for the incorporation of RNAs that may hold signalling potential. [ABSTRACT FROM AUTHOR]

Aims: This study sought to assess the effect of treatment of sacubitril/valsartan (S/V) on improving cardiac function and reversing cardiac remodelling in patients with acute coronary syndrome (ACS) complicated with heart failure with reduced ejection fraction after percutaneous coronary intervention (PCI). Methods and results: We enrolled 275 ACS patients with reduced left ventricular ejection fraction after PCI. The patients were divided into the routine and S/V groups according to the treatment drugs. The symptoms, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) concentrations, echocardiographic parameters [left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left ventricular end‐diastolic volume index (LVEDVI), and left ventricular end‐systolic volume index (LVESVI)], major adverse cardiac events (MACEs), and adverse reactions were recorded at baseline and 6 months after treatment when a clinical follow‐up was performed. The S/V group was further divided into prespecified subgroups including unstable angina (UA) group, non‐ST‐elevation myocardial infarction (NSTEMI) group, and ST‐elevation myocardial infarction (STEMI) group according to the type of ACS. We analysed the changes in LVEF, LVMI, LVEDVI, LVESVI, and NT‐proBNP in both groups and evaluated the correlation between the changes in the above variables (ΔLVEF, ΔLVMI, ΔLVEDVI, ΔLVESVI, and ΔNT‐proBNP). Cox regression model was used to assess the independent risk factors of MACE. Prespecified subgroup analyses were also conducted. Compared with baseline, LVEF increased significantly (P < 0.05), NT‐proBNP, LVMI, and LVESVI decreased significantly in both groups after 6 months (P < 0.05), and LVEDVI decreased significantly in the S/V group (P = 0.001). In the S/V group, ΔLVEF (t = −2.745, P = 0.006), ΔNT‐proBNP (P = 0.009), ΔLVEDVI (t = 4.203, P = 0.001), and ΔLVESVI (t = 3.907, P = 0.001) were significantly improved than those in the routine group. In the S/V group, ΔLVEF was negatively correlated with ΔNT‐proBNP (r = −0.244, P = 0.004), ΔLVMI (r = −0.190, P = 0.028), ΔLVEDVI (r = −0.173, P = 0.045), and ΔLVESVI (r = −0.261, P = 0.002). In Cox regression model analysis, ΔLVEF {hazard ratio [HR] = 0.87 [95% confidence interval (CI) 0.80–0.95], P = 0.003}, ΔLVEDVI [HR = 1.04 (95% CI 1.01–1.06), P = 0.013], and ΔLVESVI [HR = 1.04 (95% CI 1.01–1.08), P = 0.026] were independent risk factors for MACE. Subgroup analysis showed that ΔLVEF (t = 6.290, P = 0.001), ΔLVEDVI (t = 2.581, P = 0.011), and ΔNT‐proBNP (P = 0.019) in the NSTEMI group were significantly improved than those in the UA group, ΔLVEDVI in the NSTEMI group was significantly better than that in the STEMI group (t = −3.365, P = 0.001), and ΔLVEF in the STEMI group was significantly better than that in the UA group (t = −3.928, P = 0.001). There was a significant difference in the survival probability without MACE among the three groups in the analysis of the Kaplan–Meier curve (P = 0.042). The incidence of MACE in the UA group was significantly higher than that in the NSTEMI group (32.4% vs. 6.3%, P = 0.004). Conclusions: The cardiac function is improved and cardiac remodelling is reversed significantly after treatment of S/V in ACS patients with reduced left ventricular ejection fraction after PCI, and the improvement is more obvious than the routine group. There is a significant negative correlation between the change in LVEF and the changes in NT‐proBNP, LVMI, LVEDVI, and LVESVI. The increase of LVEF and the decrease of LVEDVI and LVESVI are protective factors to improve the prognosis. Patients with myocardial infarction and reduced left ventricular ejection fraction might benefit more from the initiation of S/V as first‐line heart failure treatment after PCI. [ABSTRACT FROM AUTHOR]

Hydroxyapatites have been investigated since past six decades as laser host materials. Because of their important roles in bone and teeth, these have been subjects of recent investigations. Gallium and titanium have great potential for decreasing the depletion of calcium and reducing osteoporosis. The electrical properties and polarity play important roles in regeneration of the bones. We observed growth of grains in selenium‐doped gallium and titanium containing silicate hydroxyapatites. Observed morphology showed non‐facetted microstructures and it helped in achieving larger grains. For the material processed for the period of longer than 70 h, we did not observe any difference in the dielectric constant and resistivity of the selenium‐doped materials. For irradiating the materials, a Cs‐137 γ‐radiation with 5 µm curie dose was used up to 100 h. We observed that the dielectric constant and resistivity at different frequencies ranging from 100 to 100 000 Hz were affected by the high energy radiation. However, bias voltage in the range of 50–1 000 mV did no alter the dielectric constant or resistivity. This indicated that the breakdown of the material did not occur for this bias range. [ABSTRACT FROM AUTHOR]

Background: This systematic review and meta‐analysis aimed to summarize evidence regarding the effectiveness and safety of oral antibiotic intervention for chronic low back pain (CLBP) patients with/without type‐1 Modic changes (MC1). Methods: AMED, CINAHL, Cochrane Library, Embase, and Medline were searched from inception to March 3, 2023. Randomized controlled trials (RCTs) or non‐RCTs that investigated the effectiveness or safety of oral antibiotics in treating CLBP patients were eligible for inclusion. Two independent reviewers screened abstracts, full‐text articles, and extracted data. The methodological quality of each included article were evaluated by RoB2 and NIH quality assessment tools. The quality of evidence was appraised by GRADE. Meta‐analyses were performed, where applicable. A subgroup analysis was conducted to evaluate the RCTs and case series separately, and to evaluate the effect of removing a low‐quality RCT. Results: Three RCTs and four case series were included. All Amoxicillin‐clavulanate/Amoxicillin treatments lasted for approximately 3 months. Moderate‐ and low‐quality evidence suggested that antibiotic was significantly better than placebo in improving disability and quality of life in CLBP patients with MC1 at 12‐month follow‐up, respectively. Low‐quality evidence from meta‐analyses of RCTs showed that oral antibiotic was significantly better than placebo in improving pain and disability in CLBP patients with MC1 immediately post‐treatment. Very low‐quality evidence from the case series suggested that oral Amoxicillin‐clavulanate significantly improved LBP/leg pain, and LBP‐related disability. Conversely, low‐quality evidence found that oral Amoxicillin alone was not significantly better than placebo in improving global perceived health in patients with CLBP at the 12‐month follow‐up. Additionally, oral antibiotic users had significantly more adverse effects than placebo users. Conclusions: Although oral antibiotics were statistically superior to placebo in reducing LBP‐related disability in patients with CLBP and concomitant MC1, its clinical significance remains uncertain. Future large‐scale high‐quality RCTs are warranted to validate the effectiveness of antibiotics in individuals with CLBP. [ABSTRACT FROM AUTHOR]

Like the fruits of Elaeis guineensis, the seeds of Acacia holosericea have two types of oils. One is present in the yellow aril (56%), which is attached to the black seed, and the other is in the kernel of the seed (12%). The proximate composition of seed and the physicochemical characteristics of the solvent-extracted oils are reported. The aril fat is quite different from the seed oil in all respects. In descending order, the major fatty acids in aril fat are 18∶1 (54.35%), 16∶0 (29.3%), and 18∶2 (8.0%), whereas in seed (−aril) oil, the order is 18∶2 (59.45%) 18∶1 (20.2%), and 16∶0 (10.0%). In whole seed (+aril) oil, the order is 18∶2 (53.3%), 18∶1 (25%), 16∶0 (12.6). [ABSTRACT FROM AUTHOR]

Electronic textiles (e‐textiles) have emerged as a revolutionary solution for personalized healthcare, enabling the continuous collection and communication of diverse physiological parameters when seamlessly integrated with the human body. Among various methods employed to create wearable e‐textiles, printing offers unparalleled flexibility and comfort, seamlessly integrating wearables into garments. This has spurred growing research interest in printed e‐textiles, due to their vast design versatility, material options, fabrication techniques, and wide‐ranging applications. Here, a comprehensive overview of the crucial considerations in fabricating printed e‐textiles is provided, encompassing the selection of conductive materials and substrates, as well as the essential pre‐ and post‐treatments involved. Furthermore, the diverse printing techniques and the specific requirements are discussed, highlighting the advantages and limitations of each method. Additionally, the multitude of wearable applications made possible by printed e‐textiles is explored, such as their integration as various sensors, supercapacitors, and heated garments. Finally, a forward‐looking perspective is provided, discussing future prospects and emerging trends in the realm of printed wearable e‐textiles. As advancements in materials science, printing technologies, and design innovation continue to unfold, the transformative potential of printed e‐textiles in healthcare and beyond is poised to revolutionize the way wearable technology interacts and benefits. [ABSTRACT FROM AUTHOR]

Objectives: There is no clear consensus so far on which fixation method is most favorable for the tibial tunnel in anterior cruciate ligament reconstruction (ACLR). The purpose of this paper is to investigate the outcome of RigidFix cross pins fixation in the tibial tunnel and to explore the advantages of RigidFix applied both in the femoral and tibial tunnel with hamstring tendon graft in anterior cruciate ligament reconstruction. Methods: This retrospective study included 53 patients (male/female, 45/8) who underwent anterior cruciate ligament reconstruction using autologous hamstring tendons between January 2013 and December 2017 at our institute. The participants in group A (n = 36) received anterior cruciate ligament reconstruction with RigidFix cross pins fixation in both femoral and tibial tunnels, while those in group B (n = 17) with RigidFix cross pins fixation in the femoral tunnel and Interference screw fixation in the tibial tunnel. The visual analogue scale (VAS) score, International Knee Documentation Committee subjective knee form 2000 (IKDC2000) score, Lysholm knee scoring scale, Tegner activity score and the side‐to‐side difference were compared at 2 and 5 years postoperatively. The graft diameter, number of strands in graft and the average diameter of each strand were also compared between the two groups. The categorical parameters were analyzed by chi‐square test and the continuous variables conforming to a normal distribution were analyzed by Student's t‐test. Results: At 2 years postoperation, the VAS score (1.61 ± 0.55), side‐to‐side difference (1.50 ± 0.58) in group A were significantly lower than that in group B, and the IKDC2000 score (88.81 ± 3.88), Tegner activity score (6.14 ± 0.60) in group A were significantly higher than that in group B. At 5 years postoperation, the VAS score (1.64 ± 0.68), side‐to‐side difference (1.73 ± 0.63) in group A were significantly lower than that in group B, and the IKDC2000 score (89.09 ± 3.85), Tegner activity score (6.58 ± 0.94) in group A were slso significantly higher than that in group B. There was statistical difference in the change of the side‐to‐side difference between the two groups (group A vs. B, 0.22 ± 0.08 vs. 0.34 ± 0.11, p < 0.001). There were also statistical differences in the graft diameter (group A vs. B, 7.83 ± 0.74 vs. 7.41 ± 0.51, p = 0,038), number of strands in graft (5.67 ± 0.72 vs. 4.00 ± 0.00, p < 0.001) and the average diameter of each strand (1.41 ± 0.22 vs. 1.85 ± 0.13, p < 0.001) between the two groups. Conclusion: RigidFix cross pins fixation in the tibial tunnel for anterior cruciate ligament reconstruction can achieve better 5‐year results when compared with the interference screw, and the hamstring tendon can be folded into a thicker graft when RigidFix cross pins were applied in both femoral and tibial tunnels. [ABSTRACT FROM AUTHOR]

Food is fundamental for the survival of organisms, governing growth, maintenance, and reproduction through the provision of essential macronutrients. However, access to food with optimum macronutrient composition, which will maximize the evolutionary fitness of an organism, is not always guaranteed. This leads to dietary mismatches with potential impacts on organismal performance. To understand the consequences of such dietary mismatches, we examined the effects of isocaloric diets varying in macronutrient composition on eight key organismal traits spanning across the lifespan of a large outbred Drosophila melanogaster population (n ~ 2500). Our findings reveal that carbohydrate‐reduced isocaloric diets correlates to accelerated pre‐adult development and boosts reproductive output without impacting pre‐adult viability and body size. Conversely, an elevated dietary carbohydrate content correlated to reduced lifespan in flies, evidenced by accelerated functional senescence including compromised locomotor activity and deteriorating gut integrity. Furthermore, transcriptomic analysis indicated a substantial difference in gene regulatory landscapes between flies subject to high‐carbohydrate versus high‐protein diet, with elevated protein levels indicating transcriptomes primed for reduced synthesis of fatty acids. Taken together, our study helps advance our understanding of the effect of macronutrient composition on life history traits and their interrelations, offering critical insights into potential adaptive strategies that organisms might adopt against the continual dietary imbalances prevalent in the rapidly evolving environment. [ABSTRACT FROM AUTHOR]

Inducible defences can improve survival in variable environments by allowing individuals to produce defences if they detect predators. These defences are often expressed as inter‐related developmental, morphological, and behavioural changes. However, producing defences can incur costs, which may be expressed immediately and/or during subsequent life stages. In Australia, waterborne cues of potentially cannibalistic conspecific tadpoles induce hatchlings of invasive cane toads to accelerate their developmental rate, thereby reducing their window of vulnerability. However, the mechanisms and costs of such accelerated development are poorly understood, and whether cane toad embryos show cannibal‐induced plasticity in other traits is unknown. Here, we found no evidence of altered time of hatching for embryos exposed to non‐feeding conspecific cannibal tadpole cues. Additionally, hatchling dispersal behaviours were not affected by exposure to these cues. However, developmental acceleration of hatchlings induced by exposure to tadpole cues was accompanied by reduced hatchling growth, indicating a trade‐off between these processes. At the conclusion of the hatchling stage, cannibal‐exposed individuals were smaller and morphologically distinct from control siblings. This size reduction affected performance during the subsequent tadpole stage: smaller cannibal‐exposed individuals were more likely to die, and initial size tended to be positively associated with subsequent tadpole growth and development across treatments (respectively, p =.07 and p =.06). However, even accounting for variation in initial size, there was an additional negative effect of cannibal exposure on tadpole growth and development, demonstrating that the fitness costs associated with developmental acceleration are not entirely attributable to size reductions. [ABSTRACT FROM AUTHOR]

ZnAl2O4 is a cubic close‐packed oxide with tetrahedral and octahedral sites in the lattice structure. The catalytic activity of ZnAl2O4 is strongly connected with the surface properties caused by the partially inverse spinel ZnAl2O4 structure. In this research, ZnAl2O4 catalysts are prepared for the glycerolysis of urea via the polymeric citrate complex method using polymeric templates made of citric acid with a different polyol precursor. Depending on the polyol precursor, the partial inversion parameters representing the disordered bulk ZnAl2O4 structure are controlled, which results in different surface AlO4/AlO6 ratios and surface acidity. The specific surface areas of the prepared ZnAl2O4 catalysts are proportional to the molecular weight of the polyol precursor. The s–ZnAl2O4 (polyol precursor = sorbitol) prepared via two pathways from citrate complex and polymeric citrate complex shows the highest inversion parameter and surface acidity, leading to the highest glycerol carbonate (GC) yield and glycerol conversion in the glycerolysis of urea. A relationship between the GC yield and the surface properties, such as the acidity and inversion parameters, is established. [ABSTRACT FROM AUTHOR]

Background: New Zealand's (NZ) complete absence of community transmission of influenza and respiratory syncytial virus (RSV) after May 2020, likely due to COVID‐19 elimination measures, provided a rare opportunity to assess the impact of border restrictions on common respiratory viral infections over the ensuing 2 years. Methods: We collected the data from multiple surveillance systems, including hospital‐based severe acute respiratory infection surveillance, SHIVERS‐II, ‐III and ‐IV community cohorts for acute respiratory infection (ARI) surveillance, HealthStat sentinel general practice (GP) based influenza‐like illness surveillance and SHIVERS‐V sentinel GP‐based ARI surveillance, SHIVERS‐V traveller ARI surveillance and laboratory‐based surveillance. We described the data on influenza, RSV and other respiratory viral infections in NZ before, during and after various stages of the COVID related border restrictions. Results: We observed that border closure to most people, and mandatory government‐managed isolation and quarantine on arrival for those allowed to enter, appeared to be effective in keeping influenza and RSV infections out of the NZ community. Border restrictions did not affect community transmission of other respiratory viruses such as rhinovirus and parainfluenza virus type‐1. Partial border relaxations through quarantine‐free travel with Australia and other countries were quickly followed by importation of RSV in 2021 and influenza in 2022. Conclusion: Our findings inform future pandemic preparedness and strategies to model and manage the impact of influenza and other respiratory viral threats. [ABSTRACT FROM AUTHOR]

Uranium (U) is an important global energy resource and a redox sensitive trace element that reflects changing environmental conditions and geochemical cycling. The redox evolution of U mineral chemistry can be interrogated to understand the formation and distribution of U deposits and the redox processes involved in U geochemistry throughout Earth history. In this study, geochemical modeling using thermodynamic data, and mineral chemistry network analysis are used to investigate U geochemistry and deposition through time. The number of U6+ mineral localities surpasses the number of U4+ mineral localities in the Paleoproterozoic. Moreover, the number of sedimentary U6+ mineral localities increases earlier in the Phanerozoic than the number of U4+ sedimentary mineral localities, likely due to the necessity of sufficient sedimentary organic matter to reduce U6+–U4+. Indeed, modeling calculations indicate that increased oxidative weathering due to surface oxygenation limited U4+ uraninite (UO2) formation from weathered granite and basalt. Louvain network community detection shows that U6+ forms minerals with many more shared elements and redox states than U4+. The range of weighted Mineral Element Electronegativity Coefficient of Variation (wMEECV) values of U6+ minerals increases through time, particularly during the Phanerozoic. Conversely, the range of wMEECV values of U4+ minerals is consistent through time due to the relative abundance of uraninite, coffinite, and brannerite. The late oxidation and formation of U6+ minerals compared to S6+ minerals illustrates the importance of the development of land plants, organic matter deposition, and redox‐controlled U deposition from ground water in continental sediments during this time‐period. Plain Language Summary: Uranium (U) is the most widely used fuel in nuclear fission power plants, and nuclear power results in lower greenhouse gas emissions than fossil fuel energy. The different types of U deposits and minerals have evolved throughout the Earth history with changing environmental conditions and formation processes. In this study, we use modeling calculations and network analysis to understand how the transforming Earth system impacted the global U cycle, evolving U mineral chemistry, and deposit formation through time. Modeling calculations show that the abundant U mineral uraninite (UO2) formed in much greater quantities in the anoxic conditions of the Archean eon than present day oxic conditions. We also find that U minerals are increasingly oxidized through time, in agreement with modeling calculations, resulting in new minerals with diversifying chemical element associations and expanding distribution of U in the environment. The earlier increase in the number of oxidized U minerals in sedimentary localities than unoxidized U minerals in sedimentary localities 350–250 million years ago reflects the importance of land plants and organic matter in the formation of unoxidized U minerals in sedimentary settings. Key Points: Model calculations indicate Earth surface oxidation limited U4+ uraninite formation, in agreement with increased observed U6+ mineralsU oxidation increases the diversity of mineral chemical element associations and distribution in the environmentThe later formation of U6+ minerals compared to S6+ minerals represents differential Earth surface oxidation [ABSTRACT FROM AUTHOR]

Background: Endothelial cell migration is the initial stage of angiogenesis. In previous studies, miR‐9 has been found to regulate angiogenesis and cell migration in human medicine. Objectives: This study aimed to reveal the regulatory effect of miR‐9 on canine endothelial cell migration. Methods: Embryonic canine ventricle myocardium tissues were collected and induced to differentiate into endothelial‐like cells (ELCs). A transwell and invasion assay were used to evaluate the impact of miR‐9 on the migration capacity of ELCs, after which a luciferase reporter assay, western blotting, RNA sequencing and reverse transcription‐polymerase chain reaction were conducted to explore the regulatory mechanism. Results: Our results showed that we successfully induced the primary cells derived from canine cardiac embryo tissues into ELCs. MiR‐9 also promoted the migration and invasion of canine ELCs, and inhibited the expression of collagen XV, an angiogenic inhibitor, at the translational level by targeting the 3′ untranslated region of COL15A1 gene. Furthermore, RNA sequencing showed that overexpression of miR‐9 impacted several signalling pathways and eight genes involved in angiogenesis and cell migration in canine ELCs. Conclusions: These findings suggest that miR‐9 enhances the migration of canine ELCs and may serve as a potential diagnostic and therapeutic target for canine diseases involved in endothelial cells migration and angiogenesis, but more further studies are needed. [ABSTRACT FROM AUTHOR]

Root‐knot nematodes (RKNs) inflict extensive damage to global agricultural production. Intercropping has been identified as a viable agricultural tool for combating RKNs, but the mechanisms by which intercropped plants modulate RKN parasitism are still not well understood. Here, we focus on the cucumber–amaranth intercropping system. We used a range of approaches, including the attraction assay, in vitro RNA interference (RNAi), untargeted metabolomics, and hairy root transformation, to unveil the mechanisms by which weak host plants regulate Meloidogyne incognita chemotaxis towards host plants and control infection. Amaranth roots showed a direct repellence to M. incognita through disrupting its chemotaxis. The in vitro RNAi assay demonstrated that the Mi‐flp‐1 and Mi‐flp‐18 genes (encoding FMRFamide‐like peptides) regulated M. incognita chemotaxis towards cucumber and controlled infection. Moreover, M. incognita infection stimulated cucumber and amaranth to accumulate distinct metabolites in both root tissues and rhizosphere soils. In particular, naringenin and salicin, enriched specifically in amaranth rhizosphere soils, inhibited the expression of Mi‐flp‐1 and Mi‐flp‐18. In addition, overexpression of genes involved in the biosynthesis of pantothenic acid and phloretin, both of which were enriched specifically in amaranth root tissues, delayed M. incognita development in cucumber hairy roots. Together, our results reveal that both the distinct host status and disruption of chemotaxis contribute to M. incognita inhibition in intercropping. [ABSTRACT FROM AUTHOR]

Cells can communicate via the release and uptake of extracellular vesicles (EVs), which are nano‐sized membrane vesicles that can transfer protein and RNA cargo between cells. EVs contain microRNAs and various other types of non‐coding RNA, of which Y RNA is among the most abundant types. Studies on how RNAs and their binding proteins are sorted into EVs have mainly focused on comparing intracellular (cytoplasmic) levels of these RNAs to the extracellular levels in EVs. Besides overall transcriptional levels that may regulate sorting of RNAs into EVs, the process may also be driven by local intracellular changes in RNA/RBP concentrations. Changes in extracellular Y RNA have been linked to cancer and cardiovascular diseases. Although the loading of RNA cargo into EVs is generally thought to be influenced by cellular stimuli and regulated by RNA binding proteins (RBP), little is known about Y RNA shuttling into EVs. We previously reported that immune stimulation alters the levels of Y RNA in EVs independently of cytosolic Y RNA levels. This suggests that Y RNA binding proteins, and/or changes in the local Y RNA concentration at EV biogenesis sites, may affect Y RNA incorporation into EVs. Here, we investigated the subcellular distribution of Y RNA and Y RNA binding proteins in activated and non‐activated THP1 macrophages. We demonstrate that Y RNA and its main binding protein Ro60 abundantly co‐fractionate in organelles involved in EV biogenesis and in EVs. Cellular activation led to an increase in Y RNA concentration at EV biogenesis sites and this correlated with increased EV‐associated levels of Y RNA and Ro60. These results suggest that Y RNA incorporation into EVs may be controlled by local intracellular changes in the concentration of Y RNA and their protein binding partners. [ABSTRACT FROM AUTHOR]

Bone injuries such as fractures are one major cause of morbidities worldwide. A considerable number of fractures suffer from delayed healing, and the unresolved acute pain may transition to chronic and maladaptive pain. Current management of pain involves treatment with NSAIDs and opioids with substantial adverse effects. Herein, we tested the hypothesis that the purine molecule, adenosine, can simultaneously alleviate pain and promote healing in a mouse model of tibial fracture by targeting distinctive adenosine receptor subtypes in different cell populations. To achieve this, a biomaterial‐assisted delivery of adenosine is utilized to localize and prolong its therapeutic effect at the injury site. The results demonstrate that local delivery of adenosine inhibited the nociceptive activity of peripheral neurons through activation of adenosine A1 receptor (ADORA1) and mitigated pain as demonstrated by weight bearing and open field movement tests. Concurrently, local delivery of adenosine at the fracture site promoted osteogenic differentiation of mesenchymal stromal cells through adenosine A2B receptor (ADORA2B) resulting in improved bone healing as shown by histological analyses and microCT imaging. This study demonstrates the dual role of adenosine and its material‐assisted local delivery as a feasible therapeutic approach to treat bone trauma and associated pain. [ABSTRACT FROM AUTHOR]

In recent years, the extraction, processing, and application of edible gums, in the food and healthcare sector has skyrocketed and extensively explored. Edible gums are derived from multiple sources such as plants/trees, animals, microorganisms, and seaweed. Edible gums are typically employed to perform certain functions including modification of rheology, gel formation, stability, encapsulation, and fat replacement. The unique interaction of edible gums with food molecules enables the achievement of desired characteristics of specific food products belonging to various sectors. This review delivers a comprehensive understanding of the classification and characterization of edible gums and their applications in the food industry. Despite several advantages offered by edible gums, there exist certain challenges that are encountered during commercialization by manufacturers and proposed strategies to overcome the hurdles, regulatory aspects, and safety of edible gums upon consumption have been highlighted in this review. [ABSTRACT FROM AUTHOR]

Main Problem: N‐acetylaspartylglutamate (NAAG) has neuroprotective effects in traumatic brain injury (TBI) by activating metabotropic glutamate receptor 3 (mGluR3) and reducing glutamate release. Glutamate carboxypeptidase II (GCPII) is the primary enzyme responsible for the hydrolysis of NAAG. It remains unclear whether glutamate carboxypeptidase III (GCPIII), a homolog of GCPII, can partially compensate for GCPII's function. Methods: GCPII−/−, GCPIII−/−, and GCPII/III−/− mice were generated using CRISPR/Cas9 technology. Mice brain injury model was established through moderate controlled cortical impact (CCI). The relationship between GCPII and GCPIII was explored by analyzing injury response signals in the hippocampus and cortex of mice with different genotypes at the acute (1 day) and subacute (7 day) phase after TBI. Results: In this study, we found that deletion of GCPII reduced glutamate production, excitotoxicity, and neuronal damage and improved cognitive function, but GCPIII deletion had no significant neuroprotective effect. Additionally, there was no significant difference in the neuroprotective effect between the combination of GCPII and GCPIII deletion and GCPII deletion alone. Conclusion: These results suggest that GCPII inhibition may be a therapeutic option for TBI, and that GCPIII may not act as a complementary enzyme to GCPII in this context. [ABSTRACT FROM AUTHOR]

In a mobile ad hoc network (MANET), all nodes are communicated with one another across wireless networks to create a temporary network without the support of centralised management. Due to dynamic topology in MANET, secure routing is a crucial issue. The existing secure routing protocol and their security concerns are analysed in this work. The suggested Swarm Intelligence‐based Secure Ad‐hoc On‐demand Distance Vector (SIS‐AODV) algorithm offers security by applying a secret key and hash mechanism to prevent the involvement of malicious nodes in routing operations. A secure routing system of MANET guards against internal and external network attacks. The proposed SIS‐AODV algorithm consists of two sections: the secret key value generated by applying Elliptical Curve Cryptography (ECC)‐based algorithm and the PRESENT algorithm to encrypt the data packets. Besides, authentication and non‐repudiation are applied using the H‐PRESENT 128 algorithm. The PRESENT algorithm and H‐PRESENT 128 hash function require less computational power. Centralised management is optional in this scheme, so overhead decreases. The second section of SIS‐AODV consists of Ant Colony Grey Wolf Optimization over the AODV algorithm to improve network performance while implementing a security algorithm over MANET. Analysis results show maximum performance with a packet delivery ratio of 98% and throughput of 85%. In addition, end‐to‐end delay is reduced by up to 25%, and routing overhead decreases by up to 20%. Keywords: AODV, Elliptical Curve, PRESENT, H‐PRESENT, Euclidean Algorithm, ACO, GWO, Blackhole attack. [ABSTRACT FROM AUTHOR]

Recently established heart failure therapies, including sodium glucose co‐transporter 2 inhibitors, angiotensin‐neprilysin inhibitors, and cardiac resynchronization therapy, have led to both clinical and structural improvements. Reverse remodelling describes the structural and functional responses to therapy and has been shown to correlate with patients' clinical response, acting as a biomarker for treatment success. The introduction of these new therapeutic agents in addition to advances in non‐invasive cardiac imaging has led to an expansion in the evaluation and the validation of cardiac reverse remodelling. Methods including volumetric changes as well as strain and myocardial work have all been shown to be non‐invasive end‐points of reverse remodelling, correlating with clinical outcomes. Our review summarizes the current available evidence on reverse remodelling in heart failure by the non‐invasive cardiac imaging techniques, in particular transthoracic echocardiography. [ABSTRACT FROM AUTHOR]

Extracellular vesicle (EV)-carried miRNAs can influence gene expression and functional phenotypes in recipient cells. Argonaute 2 (Ago2) is a key miRNA-binding protein that has been identified in EVs and could influence RNA silencing. However, Ago2 is in a non-vesicular form in serum and can be an EV contaminant. In addition, RNA-binding proteins (RBPs), including Ago2, and RNAs are often minor EV components whose sorting into EVs may be regulated by cell signaling state. To determine the conditions that influence detection of RBPs and RNAs in EVs, we evaluated the effect of growth factors, oncogene signaling, serum, and cell density on the vesicular and nonvesicular content of Ago2, other RBPs, and RNA in small EV (SEV) preparations. Media components affected both the intravesicular and extravesicular levels of RBPs andmiRNAs in EVs,with serumcontributing strongly to extravesicular miRNA contamination. Furthermore, isolation of EVs from hollow fiber bioreactors revealed complex preparations, with multiple EV-containing peaks and a large amount of extravesicular Ago2/RBPs. Finally, KRAS mutation impacts the detection of intra- and extra-vesicular Ago2. These data indicate that multiple cell culture conditions and cell states impact the presence of RBPs in EV preparations, some of which can be attributed to serumcontamination. [ABSTRACT FROM AUTHOR]

The molecular heterogeneity of extracellular vesicles (EVs) and the co-isolation of physically similar particles, such as lipoproteins (LPs), confounds and limits the sensitivity of EV bulk biomarker characterization. Herein, we present a single-EV and particle (siEVP) protein and RNA assay (siEVPPRA) to simultaneously detectmRNAs, miRNAs, and proteins in subpopulations of EVs and LPs. The siEVPPRA immobilizes and sorts particles via positive immunoselection onto micropatterns and focuses biomolecular signals in situ. By detecting EVPs at a single-particle resolution, the siEVPPRA outperformed the sensitivities of bulk-analysis benchmark assays for RNA and protein. To assess the specificity of RNA detection in complex biofluids, EVs from various glioma cell lines were processed with small RNA sequencing, whereby two mRNAs and two miRNAs associated with glioblastoma multiforme (GBM) were chosen for cross-validation. Despite the presence of single-EV-LP co-isolates in serum, the siEVPPRA detected GBM-associated vesicular RNA profiles in GBM patient siEVPs. The siEVPPRA effectively examines intravesicular, intervesicular, and interparticle heterogeneity with diagnostic promise. [ABSTRACT FROM AUTHOR]

Larval crowding is one common ecological stressor for many insect species. In Drosophila, high larval density alters multiple widely‐studied phenotypes including life‐history traits, morphology and behavior. Nevertheless, we still miss a holistic view of the full range of phenotypic changes and the underlying molecular mechanisms. In this study, we analyzed the adult transcriptomes of high and low larval density fly cohorts, and highlighted the molecular basis of the plastic traits. Increased cellular energy metabolism and locomotion, along with reduced reproductive investment, are key responses to high larval density. Moreover, we compared the expression changes among cohorts with different developmental delays caused by larval crowding. The majority of genes induced by larval crowding showed the strongest expression alterations in cohorts with intermediate delay. Furthermore, linear expression changes were observed in genes related to nutrition and detoxification. Comparing different high‐density cohorts could provide insights into the varied responses to distinct larval crowding‐induced stresses such as space competition, food degradation and waste accumulation. [ABSTRACT FROM AUTHOR]

Vaccination programmes provide a safe, effective and cost‐efficient strategy for maintaining population health. In veterinary medicine, vaccination not only reduces disease within animal populations but also serves to enhance public health by targeting zoonoses. Nevertheless, for many pathogens, an effective vaccine remains elusive. Recently, nanovaccines have proved to be successful for various infectious and non‐infectious diseases of animals. These novel technologies, such as virus‐like particles, self‐assembling proteins, polymeric nanoparticles, liposomes and virosomes, offer great potential for solving many of the vaccine production challenges. Their benefits include low immunotoxicity, antigen stability, enhanced immunogenicity, flexibility sustained release and the ability to evoke both humoral and cellular immune responses. Nanovaccines are more efficient than traditional vaccines due to ease of control and plasticity in their physio‐chemical properties. They use a highly targeted immunological approach which can provide strong and long‐lasting immunity. This article reviews the currently available nanovaccine technology and considers its utility for both infectious diseases and non‐infectious diseases such as auto‐immunity and cancer. Future research opportunities and application challenges from bench to clinical usage are also discussed. [ABSTRACT FROM AUTHOR]