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Acute stress normally engages descending brain pathways to produce an antinociceptive response, known as stress‐induced analgesia. Paradoxically, these descending pain modulatory pathways are also involved in the maintenance of the abnormal pain associated with chronic neuropathic pain. It remains unclear how stress‐induced analgesia is affected by neuropathic pain states. We therefore examined the impact of a chronic constriction nerve‐injury (CCI) model of neuropathic pain on restraint stress‐induced analgesia in C57BL/6 mice. Thirty minutes of restraint stress produced analgesia in the hotplate thermal nociceptive assay that was less in CCI compared to control mice who underwent a sham‐surgery. In sham but not CCI mice, stress‐induced analgesia was reduced by the opioid receptor antagonist naltrexone. The cannabinoid CB1 receptor antagonist AM281 did not affect stress‐induced analgesia in either sham or CCI mice. Low‐dose pre‐treatment with the dual fatty acid amide hydrolase and monoacylglycerol lipase inhibitor JZL195 increased stress‐induced analgesia in CCI but not sham mice. The JZL195 enhancement of stress‐induced analgesia in CCI mice was abolished by AM281 but was unaffected by naltrexone. These findings indicate that the acute opioid‐mediated analgesic response to a psychological stressor is disrupted in a nerve‐injury model of neuropathic pain. Importantly, this impairment of stress‐induced analgesia was rescued by blockade of endocannabinoid breakdown via a cannabinoid CB1 receptor dependent mechanism. These findings suggest that subthreshold treatment with endocannabinoid degradation blockers could be used to alleviate the disruption of endogenous pain control systems in a neuropathic pain state. [ABSTRACT FROM AUTHOR]

Independent Zimbabwe has experienced continual episodes of mostly violent intra-state conflict that have left the country polarised and divided along mostly ethnic, racial, and class lines. In the aftermath of each conflictual episode, peacemaking attempts have been implemented to secede hostilities, however, these attempts have only built peace at the superstructure while neglecting the grassroots, which has been the microcosm of conflict wherein most of the actors are, be they perpetrators, victims and survivors. State-led attempts at reconciliation have failed to address the after-effects of conflict, and it is the argument of this paper that endogenous approaches to relational peacebuilding cannot continue to be ignored as they can potentially address some of the fault lines. Respondents to the study were purposively selected from three provinces in the country. Findings indicate the relevance and efficacy of these approaches in building peace at the family and community levels. [ABSTRACT FROM AUTHOR]

Detection of doping with steroids that are also endogenous in the horse can be challenging, and a variety of approaches to distinguish exogenous administration from their natural presence are employed. Knowledge of endogenous concentrations of various steroids in different genders of horses (intact male, castrated male and female) and factors that could naturally affect them is beneficial for establishing ways for detection of their use. The current internationally adopted approaches include concentration‐based thresholds in urine and plasma, steroid ratios in urine and targeting the administered intact steroid esters in plasma and hair. However, these have their limitations, and therefore, other strategies, such as additional biomarkers and steroid profiling based on longitudinal testing and multivariate analysis, have been investigated and could potentially improve detection of the use of endogenous steroids in horses. This paper aims to provide a comprehensive overview of the steroids (androgens, oestrogens and progestogens) that have been reported to be endogenous to horses in literature, their concentration ranges in different genders and factors potentially affecting them as well as current and possible future approaches to detect their use. [ABSTRACT FROM AUTHOR]

In this paper, we develop discrete models of Tuberculosis (TB). This includes SEI endogenous and exogenous models without treatment. These models are then extended to a SEIT model with treatment. We develop two types of net reproduction numbers, one is the traditional R0 which is based on the disease-free equilibrium, and a new net reproduction number R0 (E*) based on the endemic equilibrium. It is shown that the disease-free equilibrium is globally asymptotically stable if R0 ≤ 1 and unstable if R0 > 1. Moreover, the endemic equilibrium is locally asymptotically stable if R0(E*) < 1 < R0. [ABSTRACT FROM AUTHOR]

A detailed study on the effects of hormones on process and larval growth from various breeding techniques will provide a better understanding of optimizing snakehead fish (Channa striata) seed production. The research aims to analyze endogenous nutrient absorption and length growth in larvae (D0-D3) from several different breeding techniques of snakehead fish (Channa striata). The study was conducted at the Freshwater Aquaculture Research Center Mandiangin, South Kalimantan. Three breeding techniques were employed: firstly, observation of naturally spawned larvae (breeding technique I) from 3 pairs of broodstock. Secondly, semi-artificial spawning using Ovaprim (breeding technique II) from 3 pairs of broodstock. Thirdly, continuation of the second treatment (rematuration) involving semi-artificial spawning using Oodev and Ovaprim (breeding technique III) from 3 pairs of broodstock.

Myo-inositol-1-phosphate synthase (MIPS) catalyzes the NAD+-dependent isomerization of glucose-6-phosphate (G6P) into inositol-1-phosphate (IMP), controlling the rate-limiting step of the inositol pathway. Previous structural studies focused on the detailed molecular mechanism, neglecting large-scale conformational changes that drive the function of this 240 kDa homotetrameric complex. In this study, we identified the active, endogenous MIPS in cell extracts from the thermophilic fungus Thermochaetoides thermophila. By resolving the native structure at 2.48 Å (FSC = 0.143), we revealed a fully populated active site. Utilizing 3D variability analysis, we uncovered conformational states of MIPS, enabling us to directly visualize an order-to-disorder transition at its catalytic center. An acyclic intermediate of G6P occupied the active site in two out of the three conformational states, indicating a catalytic mechanism where electrostatic stabilization of high-energy intermediates plays a crucial role. Examination of all isomerases with known structures revealed similar fluctuations in secondary structure within their active sites. Based on these findings, we established a conformational selection model that governs substrate binding and eventually inositol availability. In particular, the ground state of MIPS demonstrates structural configurations regardless of substrate binding, a pattern observed across various isomerases. These findings contribute to the understanding of MIPS structure-based function, serving as a template for future studies targeting regulation and potential therapeutic applications. [ABSTRACT FROM AUTHOR]

The versatility of cytochrome P450 reductase (CPR) in transferring electrons to P450s from other closely related species has been extensively exploited, e.g., by using An. gambiae CPR (AgCPR), as a homologous surrogate, to validate the role of An. funestus P450s in insecticide resistance. However, genomic variation between the AgCPR and An. funestus CPR (AfCPR) suggests that the full metabolism spectrum of An. funestus P450s might be missed when using AgCPR. To test this hypothesis, we expressed AgCPR and AfCPR side-by-side with CYP6P9a and CYP6P9b and functionally validated their role in the detoxification of insecticides from five different classes. Major variations were observed within the FAD- and NADP-binding domains of AgCPR and AfCPR, e.g., the coordinates of the second FAD stacking residue AfCPR-Y456 differ from that of AgCPR-His456. While no significant differences were observed in the cytochrome c reductase activities, when co-expressed with their endogenous AfCPR, the P450s significantly metabolized higher amounts of permethrin and deltamethrin, with CYP6P9b-AfCPR membrane metabolizing α-cypermethrin as well. Only the CYP6P9a-AfCPR membrane significantly metabolized DDT (producing dicofol), bendiocarb, clothianidin, and chlorfenapyr (bioactivation into tralopyril). This demonstrates the broad substrate specificity of An. funestus CYP6P9a/-b, capturing their role in conferring cross-resistance towards unrelated insecticide classes, which can complicate resistance management. [ABSTRACT FROM AUTHOR]

This review consolidates the evidence supporting endogenous HNO generation through enzymatic and non‐enzymatic pathways, emphasizing advancements in real‐time HNO sensing within living systems. Azanone (nitroxyl, HNO) is the one‐electron‐reduced congener of nitric oxide (NO•) and shares various biological actions. HNO exhibits unique properties, including positive inotropic and lusitropic effects, along with resistance to scavenging by reactive oxygen species (ROS), particularly superoxide. Research on HNO has intensified over the last two decades, focusing on its reactivity and the prospect of endogenous formation due to its potential significance. The high reactivity of HNO arises from reactions with biologically relevant species such as oxygen, NO•, and thiols, as well as self‐dimerization. Detecting and quantifying HNO has posed challenges, initially relying on nitrous oxide (N2O) detection, a byproduct of dimerization. Recent advancements, including fluorescent probes and a specific electrochemical nanomolar‐level sensor, have facilitated direct detection, enhancing understanding of HNO reactivity and formation. [ABSTRACT FROM AUTHOR]

Tendon injury and healing involve significant changes to tissue biology and composition. Current techniques often require animal sacrifice or tissue destruction, limiting assessment of dynamic changes in tendons, including treatment response, disease development, rupture risk, and healing progression. Changes in tendon composition, such as altered collagen content, can significantly impact tendon mechanics and function. Analyses of compositional changes typically require ex vivo techniques with animal sacrifice or destruction of the tissue. In vivo evaluation of tendons is critical for longitudinal assessment. We hypothesize that photoacoustic ultrasound detects differences in collagen concentration throughout healing. We utilized photoacoustic ultrasound, a hybrid imaging modality that combines ultrasound and laser-induced photoacoustic signals to create detailed and high-resolution images of tendons, to identify its endogenous collagen composition. We correlated the photoacoustic signal to picrosirius red staining. The results show that the photoacoustic ultrasound-estimated collagen content in tendons correlates well with picrosirius red staining. This study demonstrates that photoacoustic ultrasound can assess injury-induced compositional changes within tendons and is the first study to image these targets in rat Achilles tendon in vivo. [ABSTRACT FROM AUTHOR]

To determine the characteristics, primary sources, pathogens, risk factors, and visual outcomes in patients with endogenous endophthalmitis (EE). We performed a retrospective cohort study of 61 consecutive patients with EE (74 affected eyes) and reported on prevalence, clinical courses, prognostic factors and visual outcomes. Prevalence of EE was 5% of all patients with endophthalmitis. Among culture-positive cases (89%), Gram-positive species dominating (69%) followed by Gram-negative with 22% and fungal species with 9%. Regarding to visual outcomes, the mean visual acuity (VA, ETDRS letters) at baseline, 3-months, 6-months and 1-year follow-up was 0.85, 9, 8 and 9, respectively. Initial VA of hand movement or better (P 0.007) and bilateral infection (P 0.004) were associated with better visual outcome. The prognosis for EE remained poor despite aggressive and immediate treatment. The high suspicion, early diagnosis and prompt treatment are important factors that might lead to the better outcome. [ABSTRACT FROM AUTHOR]

Traumatic Brain Injury (TBI) is a debilitating condition that poses a significant public health concern. Historically linked to motor vehicle accidents, the epidemiology of TBI has evolved. Falls now emerge as the predominant cause, particularly among older adults. Sport-related TBIs have also garnered increased attention due to concerns regarding long-term neurological sequelae. To date, therapeutic interventions remain limited and have yet to yield substantial clinical benefits. Cell-based therapies offer promising avenues for neural repair and regeneration: endogenous stem cell therapies capitalize on endogenous pools that can be triggered by the injury and further enhanced by therapeutic approaches. In contrast, exogenous cell therapies provide an exogenous source of cells. However, challenges such as age-related decline in neurogenesis, age-related inflammation, and the heterogeneity of TBI present significant hurdles to overcome. Moreover, translating stem cell research from the laboratory to clinical applications necessitates the adherence to good manufacturing practice standards, which presents distinct obstacles. Addressing these challenges requires a multifaceted approach, including careful patient selection in clinical trials, appropriate experimental models, and the optimization of therapeutic techniques. Ultimately, a combination of strategies is likely to yield the most promising outcomes in the pursuit of effective TBI therapies. [ABSTRACT FROM AUTHOR]

Peres fish (Osteochilus kappenii) is a native freshwater fish in Central Aceh, Indonesia. This study aimed to determine the morphology and histology development of the digestive tract of Peres larvae. Understanding the developmental stages is essential to support the success of larval rearing during ontogeny. The parameters observed include the total length (TL) of larvae, daily growth rate, larval morphology, and histology of the digestive tract. Furthermore, the total length of the larvae was measured from 1 to 25 day after hatching (DAH). The larvae sampling was conducted at 1, 2, 3, 4, 8, 10, 15, 20, and 25 DAH. Morphological and histological observations were carried out microscopically, and data were analyzed descriptively. The results showed that the TL of larvae growth at the beginning (1 DAH) and termination (25 DAH) of the study was 4.58 ± 0.24 mm and 9.62 ± 0.79 mm, respectively. Based on the structural development of the body and food sources, the development of percussion larvae was divided into four phases, namely the yolk sac (0-4 DAH), pre-flexion (5-15 DAH), flexion (16-20 DAH), and post-flexion (21-25 DAH). The yolk was completely absorbed 4 DAH, marking the end of the yolk sac phase, as the Peres fish larvae began to use external feed. At 25 DAH, the larval morphology was fully formed and pigmentation spread throughout the body. The digestive organs and glands are well-developed with differentiation of the midgut and hindgut, increased goblet cells in the intestine, and increased lipid vacuoles in the liver and zymogen in the pancreas to utilize feed optimally. [ABSTRACT FROM AUTHOR]

Cyclic glycine-proline (cGP), a prevalent marine cyclic dipeptide, possesses a distinct pyrrolidine-2,5-dione scaffold, which contributes to the chemical diversity and broad bioactivities of cGP. The diverse sources from marine-related, endogenous biological, and synthetic pathways and the in vitro and in vivo activities of cGP are reviewed. The potential applications for cGP are also explored. In particular, the pivotal roles of cGP in regulating insulin-like growth factor-1 homeostasis, enhancing neuroprotective effects, and improving neurotrophic function in central nervous system diseases are described. The potential roles of this endogenous cyclic peptide in drug development and healthcare initiatives are also highlighted. This review underscores the significance of cGP as a fundamental building block in drug discovery with exceptional drug-like properties and safety. By elucidating the considerable value of cGP, this review aims to reignite interest in cGP-related research within marine medicinal chemistry and synthetic biology. [ABSTRACT FROM AUTHOR]

Traumatic Brain Injury (TBI) is a debilitating condition that poses a significant public health concern. Historically linked to motor vehicle accidents, the epidemiology of TBI has evolved. Falls now emerge as the predominant cause, particularly among older adults. Sport-related TBIs have also garnered increased attention due to concerns regarding long-term neurological sequelae. To date, therapeutic interventions remain limited and have yet to yield substantial clinical benefits. Cell-based therapies offer promising avenues for neural repair and regeneration: endogenous stem cell therapies capitalize on endogenous pools that can be triggered by the injury and further enhanced by therapeutic approaches. In contrast, exogenous cell therapies provide an exogenous source of cells. However, challenges such as age-related decline in neurogenesis, age-related inflammation, and the heterogeneity of TBI present significant hurdles to overcome. Moreover, translating stem cell research from the laboratory to clinical applications necessitates the adherence to good manufacturing practice standards, which presents distinct obstacles. Addressing these challenges requires a multifaceted approach, including careful patient selection in clinical trials, appropriate experimental models, and the optimization of therapeutic techniques. Ultimately, a combination of strategies is likely to yield the most promising outcomes in the pursuit of effective TBI therapies.

The measurement of time is not absolute; therefore, the measurement of space and time depend on the movement in space of individuals and the transformation over time of different social entities. Based on the above, this work analyzes the twin paradox with the aim of understanding how and through what cognitive processes a social asymmetry develops between two twin brothers born in a town in Malaga. The twins have been separated for ten years: One of them lives in Barcelona, in a more industrial environment, while the other, the one who remained in the town, has lived in an agricultural environment. The hypothesis of this research is that during that time – the space-time framework of ten years in which the twins have been separated and which has been perceived by them in a different way – the economic, technological and social conditions have caused social asymmetry through the perception of the reality of the two twins as they live, under their particular experiences, in different social environments. Finally, the possible social asymmetry generated between the two twins after ten years serves to reflect on the importance of the cultural factors and the economic and political institutions to smooth out the possible spatial and temporal imbalances that have shaped the particularities of social environments in which the two twins have lived.

An in situ integrated system, consisting of ecological floating islands (EFI), ecological riverbeds (ER), and ecological filter dams (EFD), was built in a ditch only receiving the effluent of sewage plant; the effect of in situ technologies on the distribution of aquatic pathogen was investigated. The results showed the aquatic pathogen decreased along the ditch. Specifically, the relative abundance of Legionella, Aeromonas, and Acinetobacter decreased from 0.032, 0.035, and 0.26 to 0.026%, 0.012%, and 0.08%, respectively. Sedimentation, filtration, and sorption (provided by plant roots and biofilms on substrates) were principal processes for the removal. The nitrogen removal bacteria to prevent the potential risk of eutrophication were also evaluated. The EFI and ER were the dominant sites for Nitrosomonas (34.96%, 32.84%) and Nitrospira (35.74%, 54.73%) enrichment, while EFI and EFD facilitated the enrichment of denitrification bacteria. Notably, the relative abundance of endogenous denitrifiers (DNB-en) (including Dechloromonas at 9.72%, Thermomonas at 0.58%, and Saccharibacteria at 2.55%) exceeded those of exogenous denitrifiers (DNB-ex) (Thauera at 0.20%, Staphylococcus at 0.005%, and Rhodobacter at 0.27%). This study demonstrated that the in situ integrated system was effective in reducing the abundance of pathogens in the drainage channel, and the deficiency of DNB-ex and carbon sources made nitrate removal difficult. [ABSTRACT FROM AUTHOR]

A large percentage (~60%) of prescription drugs and new molecular entities are designed for oral delivery, which requires passage through a semi-impervious membrane bilayer in the gastrointestinal wall. Passage through this bilayer can be dependent on membrane transporters that regulate the absorption of nutrients or endogenous substrates. Several investigations have provided links between nutrient, endogenous substrate, or drug absorption and the activity of certain membrane transporters. This knowledge has been key in the development of new therapeutics that can alleviate various symptoms of select diseases, such as cholestasis and diabetes. Despite this progress, recent studies revealed potential clinical dangers of unintended altered nutrient or endogenous substrate disposition due to the drug-mediated disruption of intestinal transport activity. This review outlines reports of glucose, folate, thiamine, lactate, and bile acid (re)absorption changes and consequent adverse events as examples. Finally, the need to comprehensively expand research on intestinal transporter-mediated drug interactions to avoid the unwanted disruption of homeostasis and diminish therapeutic adverse events is highlighted. [ABSTRACT FROM AUTHOR]

Native top-down mass spectrometry (nTDMS) has emerged as a powerful structural biology tool that can localize post-translational modifications (PTMs), explore ligand-binding interactions, and elucidate the three-dimensional structure of proteins and protein complexes in the gas-phase. Fourier-transform ion cyclotron resonance (FTICR) MS offers distinct capabilities for nTDMS, owing to its ultrahigh resolving power, mass accuracy, and robust fragmentation techniques. Previous nTDMS studies using FTICR have mainly been applied to overexpressed recombinant proteins and protein complexes. Here, we report the first nTDMS study that directly analyzes human heart tissue lysate by direct infusion FTICR MS without prior chromatographic separation strategies. We have achieved comprehensive nTDMS characterization of cardiac contractile proteins that play critical roles in heart contraction and relaxation. Specifically, our results reveal structural insights into ventricular myosin light chain 2 (MLC-2v), ventricular myosin light chain 1 (MLC-1v), and alpha-tropomyosin (α-Tpm) in the sarcomere, the basic contractile unit of cardiac muscle. Furthermore, we verified the calcium (Ca2+) binding domain in MLC-2v. In summary, our nTDMS platform extends the application of FTICR MS to directly characterize the structure, PTMs, and metal-binding of endogenous proteins from heart tissue lysate without prior separation methods. [ABSTRACT FROM AUTHOR]

Water quality deterioration and eutrophication have become a global concern, while reservoir pollution caused by multiple factors has led to frequent algal blooms, posing a serious threat to rural drinking water security and urban water supply. The purpose of this paper is to analyze the current water quality of Waihu Reservoir and use the single index method, the weighted comprehensive scoring method, and the nutrient level index method (TLI) to evaluate eutrophication. On this basis, the pollution sources of the reservoir are comprehensively analyzed and discussed, and effective control strategies are proposed. The evaluation results indicate that the reservoir is of moderate eutrophication type. Therefore, reducing the input of nutrients such as nitrogen and phosphorus in water is the main goal of alleviating exogenous pollution. The combination of engineering intervention and ecological restoration strategies to remove nutrients from the aquatic environment is an effective strategy to manage endogenous pollution. From the point of view of the source of pollution, this study provides an in-depth analysis of exogenous and endogenous pollution, respectively, and the proposed treatment is instructive for the control and routine management of eutrophication in the Waihu Reservoir, as well as for the management of similar problems in different reservoirs. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) derived from noncoding regions in the human genome were once regarded as junks with no biological significance, but recent studies have shown that these molecules are highly functional, prompting an explosion of studies on their biology. However, these recent efforts have only begun to recognize the biological significance of a small fraction (< 1%) of the lncRNAs. The basic concept of these lncRNA functions remains controversial. This controversy arises primarily from conventional biased observations based on limited datasets. Fortunately, emerging big data provides a promising path to circumvent conventional bias to understand an unbiased big picture of lncRNA biology and advance the fundamental principles of lncRNA biology. This review focuses on big data studies that break through the critical concepts of the lncRNA functional system and its endogenous regulatory roles in all cancers. lncRNAs have unique functional systems distinct from proteins, such as transcriptional initiation and regulation, and they abundantly interact with mitochondria and consume less energy. lncRNAs, rather than proteins as traditionally thought, function as the most critical endogenous regulators of all cancers. lncRNAs regulate the cancer regulatory regime by governing the endogenous regulatory network of all cancers. This is accomplished by dominating the regulatory network module and serving as a key hub and top inducer. These critical conceptual breakthroughs lay a blueprint for a comprehensive functional picture of the human genome. They also lay a blueprint for combating human diseases that are regulated by lncRNAs.

As the availability of high-frequency data becomes more widespread, it has become very popular to model random fluctuations of some econometric variables over time using Itô semi-martingale. An emblematic problem is to estimate the quadratic variation, i.e., the integrated volatility of log prices, using noisy high frequency data with endogenous time and jumps. We propose a methodology that combines the multiple sub-grids and thresholds. First, the sub-sample is used to reduce the effect of the noise. Then, the threshold method is used to get rid of the effect of jumps. Finally, the multiple sub-grids method is used to increase the convergence rate. The asymptotic properties, such as consistency and asymptotic normality, are investigated. Simulation is also included to illustrate the performance of the proposed procedure.

PurposeMaterials and MethodsResultsConclusionTo report a case of endogenous endophthalmitis caused by Sphingomonas paucimobilis in a young male.A retrospective case report.A 25-year-old male presented with reduced vision in the right eye and recurrent past episodes of hypopyon uveitis. The right eye had vision of counting fingers close to the face with cells, flare, and hypopyon in the anterior chamber with vitritis and exudates in the fundus. Blood investigations for tuberculosis, syphilis, toxoplasma, sarcoidosis, RA, ANA, HLA B27, and HLA B29 were negative. Anterior chamber tap investigations for herpes simplex viruses, varicella-zoster virus, cytomegalovirus, and toxoplasma, as well as Mycobacterium tuberculosis, yielded negative results. Ultrasound B-scan revealed a moderate number of low-reflective dot echoes in the vitreous, along with a few membranous echoes suggestive of vitritis. Blood culture and urine culture were negative. Since there was progressive deterioration, diagnostic and therapeutic vitrectomy was done with intravitreal antibiotics. The culture of the vitreous sample grew Sphingomonas paucimobilis. In the post-operative period, the patient developed retinal detachment, and re-surgery was done with a lensectomy, and the vision improved to 6/18 with contact lenses in the follow-up.This case report describes the distinct occurrence of endogenous endophthalmitis in an immunocompetent young male, which was previously reported only in peripartum cases. The clinical course is characterized by masquerading symptoms and recurrent episodes, despite the organism being of low virulence. [ABSTRACT FROM AUTHOR]

It is assumed that in the case of contact languages, it is the nonverbal context of use of these languages that may be the key factor in determining the nature of each language. Contact languages, perhaps even to a greater extent than larger or more common, the so called national languages, may establish the identity of the speech communities that use them. The text presents also selected ways in which contact languages arise, adding to the types of languages known to science, such as endogenous and exogenous contact languages, a new name for the category of languages, which are isogenic contact languages.

Nicotinamide adenine dinucleotide (NAD) is a cofactor in redox reactions and an essential mediator of energy metabolism. The redox balance between NAD+ and NADH affects various diseases, cell differentiation, and aging, and in recent years there has been a growing need for measurement techniques with improved accuracy. However, NAD(H) measurements, representing both NAD+ and NADH, have been limited by the compound's properties. We achieved highly sensitive simultaneous measurement of NAD+ and NADH under non-ion pairing, mobile phase conditions of water, or methanol containing 5 mM ammonium acetate. These were achieved using a simple pre-treatment and 7-min analysis time. Use of the stable isotope 13C5-NAD+ as an internal standard enabled validation close to BMV criteria and demonstrated the robustness of NAD(H) determination. Measurements using this method showed that brain NAD(H) levels correlate strongly with plasma NAD(H) levels in the same mouse, indicating that NAD(H) concentrations in brain tissue are reflected in plasma. As NAD(H) is involved in various neurodegenerative diseases and cerebral ischemia, as well as brain diseases such as mitochondrial myopathies, monitoring changes in NADH levels in plasma after drug administration will be useful for development of future diagnostics and therapeutics. [ABSTRACT FROM AUTHOR]

As the availability of high-frequency data becomes more widespread, it has become very popular to model random fluctuations of some econometric variables over time using Itô semi-martingale. An emblematic problem is to estimate the quadratic variation, i.e., the integrated volatility of log prices, using noisy high frequency data with endogenous time and jumps. We propose a methodology that combines the multiple sub-grids and thresholds. First, the sub-sample is used to reduce the effect of the noise. Then, the threshold method is used to get rid of the effect of jumps. Finally, the multiple sub-grids method is used to increase the convergence rate. The asymptotic properties, such as consistency and asymptotic normality, are investigated. Simulation is also included to illustrate the performance of the proposed procedure. [ABSTRACT FROM AUTHOR]

Streptococcus thermophilus has been extensively used in industrial milk fermentation. However, lack of efficient genetic manipulation approaches greatly hampered the industrial application of this species. Here, we repurposed the endogenous CRISPR1 and CRISPR3 systems, both belong to type II‐A CRISPR‐Cas9, by delivering a self‐targeting CRISPR array with DNA repair template into S. thermophilus LMD‐9. We achieved 785‐bp deletion in lacZ gene by repurposing CRISPR1 and CRISPR3 systems with efficiencies of 35% and 59%, respectively, when 1‐kb DNA repair template was provided. While providing with 1.5‐kb repair template, the editing efficiency for deletion in lacZ gene reached 90% using CRISPR3 systems. Diverse editing outcomes encompassing a stop code insertion and single nucleotide variation within lacZ, as well as a 234‐bp DNA fragment insertion upstream of ster_0903, were generated with high efficiencies of 75%–100% using the CRISPR3 system. Harnessing the customized endogenous CRISPR3 system to target six genes of eps gene cluster, we obtained six single‐gene knockout mutants with efficiencies of 29%–80%, and proved that the epsA, epsE, and epsG were the key genes affecting exopolysaccharides biosynthesis in S. thermophilus LMD‐9. Altogether, repurposing the native type II‐A CRISPR‐Cas9 can be served as a toolkit for precise genome engineering in S. thermophilus for biotechnological applications. [ABSTRACT FROM AUTHOR]

Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, β-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients. A total opioid receptor knock-out (mu, delta and kappa) and a mu-opioid receptor knock-out mouse model of RLS show circadian motor changes akin to RLS and, although both models show sensory changes, the mu-opioid receptor knock mouse shows circadian sensory changes closest to those seen in idiopathic RLS. Both models show changes in striatal dopamine, anaemia and low serum iron. However, only in the total receptor knock-out mouse do we see the decreases in serum ferritin that are normally found in RLS. There are also decreases in serum iron when wild-type mice are administered a mu-opioid receptor blocker. In addition, the mu-opioid receptor knock-out mouse also shows increases in striatal zinc paralleling similar changes in RLS. Adrenocorticotropic hormone and α-melanocyte stimulating hormone are derived from pro-opiomelanocortin as is β-endorphin. However, they cause RLS-like symptoms and periodic limb movements when injected intraventricularly into rats. These results collectively suggest that an endogenous opioid deficiency is pathogenetic to RLS and that an altered melanocortin system may be causal to RLS as well. [ABSTRACT FROM AUTHOR]

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The pathogenesis of multiple sclerosis (MS) suggests that, in genetically susceptible subjects, T lymphocytes undergo activation in the peripheral compartment, pass through the BBB, and cause damage in the CNS. They produce pro-inflammatory cytokines; induce cytotoxic activities in microglia and astrocytes with the accumulation of reactive oxygen species, reactive nitrogen species, and other highly reactive radicals; activate B cells and macrophages and stimulate the complement system. Inflammation and neurodegeneration are involved from the very beginning of the disease. They can both be affected by oxidative stress (OS) with different emphases depending on the time course of MS. Thus, OS initiates and supports inflammatory processes in the active phase, while in the chronic phase it supports neurodegenerative processes. A still unresolved issue in overcoming OS-induced lesions in MS is the insufficient endogenous activation of the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) pathway, which under normal conditions plays an essential role in mitochondria protection, OS, neuroinflammation, and degeneration. Thus, the search for approaches aiming to elevate endogenous Nrf2 activation is capable of protecting the brain against oxidative damage. However, exogenous Nrf2 activators themselves are not without drawbacks, necessitating the search for new non-pharmacological therapeutic approaches to modulate OS. The purpose of the present review is to provide some relevant preclinical and clinical examples, focusing on certain exogenous and endogenous Nrf2 activators and the modulation of therapeutic plasma exchange (TPE). The increased plasma levels of nerve growth factor (NGF) in response to TPE treatment of MS patients suggest their antioxidant potential for endogenous Nrf2 enhancement via NGF/TrkA/PI3K/Akt and NGF/p75NTR/ceramide-PKCζ/CK2 signaling pathways. [ABSTRACT FROM AUTHOR]

While there is ample evidence for the ability to selectively attend to where in space and when in time a relevant event might occur, it remains poorly understood whether spatial and temporal attention operate independently or interactively to optimize behavior. To elucidate this important issue, we provide a narrative review of the literature investigating the relationship between the two. The studies were organized based on the attentional manipulation employed (endogenous vs. exogenous) and the type of task (detection vs. discrimination). Although the reviewed findings depict a complex scenario, three aspects appear particularly important in promoting independent or interactive effects of spatial and temporal attention: task demands, attentional manipulation, and their combination. Overall, the present review provides key insights into the relationship between spatial and temporal attention and identifies some critical gaps that need to be addressed by future research. [ABSTRACT FROM AUTHOR]

Introduction: Endophthalmitis is a serious, sight-threatening purulent inflammation of the intraocular cavities of the eyeball. It greatly affects vision and can lead to severe complications such as panophthalmitis. The prevalence of endophthalmitis varies from one place to another. Aim: To identify the various aetiological and predisposing factors that contribute to endophthalmitis and to assess the visual outcomes following medical intervention (intravitreal antibiotics only) and surgical intervention (both intravitreal antibiotics and pars plana vitrectomy). Materials and Methods: The present study was conducted in the Department of Ophthalmology at Trichy SRM Medical College Hospital and Research Centre, Trichy, Tamil Nadu, India between January 2023 and February 2023. Demographic and clinical data of patients diagnosed with endophthalmitis over a two year period from October 2020 to September 2022 were collected from the Medical Records Department of the Institution for analysis. A total of 50 case records were selected using convenience sampling. Demographic details such as age, gender, predisposing risk factors, visual acuity, microbiological profiles, treatment modalities, and final visual acuity were collected from the present study. Quantitative data was presented as Mean and Standard Deviation (SD), while qualitative data was presented as frequencies and percentages. Summary statistics were analysed using Microsoft Excel version 2018. Results: In present study, 29 (58%) were males and 21 (42%) were females, with the majority falling within the age group of 50-70 years. The mean age of the sample was 53.8±16.1 years. Postoperative causes accounted for 39 (78%) of the cases, with phacoemulsification surgery with foldable intraocular lens implantation being the leading cause in 23 (58.7%) cases. Culture positivity was observed in only 22 (44%) cases, with Staphylococcus (Staph) epidermidis as the major causative organism. The best visual acuity achieved was 6/12 for two patients. Conclusion: Postoperative endophthalmitis remains the most common cause of endophthalmitis. Additionally, patients who presented with better visual acuity had a better visual outcome after treatment. Therefore, patients should be educated about the early signs of endophthalmitis to ensure prompt medical attention and improve visual recovery.

Tendon injury and healing involve significant changes to tissue biology and composition. Current techniques often require animal sacrifice or tissue destruction, limiting assessment of dynamic changes in tendons, including treatment response, disease development, rupture risk, and healing progression. Changes in tendon composition, such as altered collagen content, can significantly impact tendon mechanics and function. Analyses of compositional changes typically require ex vivo techniques with animal sacrifice or destruction of the tissue. In vivo evaluation of tendons is critical for longitudinal assessment. We hypothesize that photoacoustic ultrasound detects differences in collagen concentration throughout healing. We utilized photoacoustic ultrasound, a hybrid imaging modality that combines ultrasound and laser-induced photoacoustic signals to create detailed and high-resolution images of tendons, to identify its endogenous collagen composition. We correlated the photoacoustic signal to picrosirius red staining. The results show that the photoacoustic ultrasound-estimated collagen content in tendons correlates well with picrosirius red staining. This study demonstrates that photoacoustic ultrasound can assess injury-induced compositional changes within tendons and is the first study to image these targets in rat Achilles tendon in vivo.

Cyclic glycine-proline (cGP), a prevalent marine cyclic dipeptide, possesses a distinct pyrrolidine-2,5-dione scaffold, which contributes to the chemical diversity and broad bioactivities of cGP. The diverse sources from marine-related, endogenous biological, and synthetic pathways and the in vitro and in vivo activities of cGP are reviewed. The potential applications for cGP are also explored. In particular, the pivotal roles of cGP in regulating insulin-like growth factor-1 homeostasis, enhancing neuroprotective effects, and improving neurotrophic function in central nervous system diseases are described. The potential roles of this endogenous cyclic peptide in drug development and healthcare initiatives are also highlighted. This review underscores the significance of cGP as a fundamental building block in drug discovery with exceptional drug-like properties and safety. By elucidating the considerable value of cGP, this review aims to reignite interest in cGP-related research within marine medicinal chemistry and synthetic biology.

Bone regeneration heavily relies on bone marrow mesenchymal stem cells (BMSCs). However, recruiting endogenous BMSCs for in situ bone regeneration remains challenging. In this study, we developed a novel BMSC-aptamer (BMSC-apt) functionalized hydrogel (BMSC-aptgel) and evaluated its functions in recruiting BMSCs and promoting bone regeneration. The functional hydrogels were synthesized between maleimide-terminated 4-arm polyethylene glycols (PEG) and thiol-flanked PEG crosslinker, allowing rapid in situ gel formation. The aldehyde group-modified BMSC-apt was covalently bonded to a thiol-flanked PEG crosslinker to produce high-density aptamer coverage on the hydrogel surface. In vitro and in vivo studies demonstrated that the BMSC-aptgel significantly increased BMSC recruitment, migration, osteogenic differentiation, and biocompatibility. In vivo fluorescence tomography imaging demonstrated that functionalized hydrogels effectively recruited DiR-labeled BMSCs at the fracture site. Consequently, a mouse femur fracture model significantly enhanced new bone formation and mineralization. The aggregated BMSCs stimulated bone regeneration by balancing osteogenic and osteoclastic activities and reduced the local inflammatory response via paracrine effects. This study's findings suggest that the BMSC-aptgel can be a promising and effective strategy for promoting in situ bone regeneration.

Phytohormones play vital roles in stress modulation and enhancing the growth of plants. They interact with one another to produce programmed signaling responses by regulating gene expression. Environmental stress, including drought stress, hampers food and energy security. Drought is abiotic stress that negatively affects the productivity of the crops. Abscisic acid (ABA) acts as a prime controller during an acute transient response that leads to stomatal closure. Under long-term stress conditions, ABA interacts with other hormones, such as jasmonic acid (JA), gibberellins (GAs), salicylic acid (SA), and brassinosteroids (BRs), to promote stomatal closure by regulating genetic expression. Regarding antagonistic approaches, cytokinins (CK) and auxins (IAA) regulate stomatal opening. Exogenous application of phytohormone enhances drought stress tolerance in soybean. Thus, phytohormoneproducing microbes have received considerable attention from researchers owing to their ability to enhance drought-stress tolerance and regulate biological processes in plants. The present study was conducted to summarize the role of phytohormones (exogenous and endogenous) and their corresponding microbes in drought stress tolerance in model plant soybean. A total of n=137 relevant studies were collected and reviewed using different research databases. [ABSTRACT FROM AUTHOR]

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The paper presents an advanced exergoenvironmental and thermo-sustainability analysis of a dry process, 5-million-ton capacity cement plant with real-time operational data. The analysis was based on component-wise modelling by separating the exergy destruction (ED) into endogenous, exogenous, avoidable and unavoidable parts for the two production lines, L1 and L2. The result shows an exergy efficiency (φ ) of 55.58% for L1 and 58.22% for L2. Additionally, the overall exergoenvironmental factor (EEF) was calculated at 6.47% for (L1) and 5.89% for (L2), with the rotary kiln (RK) having the highest (EEF) of 53.7%. Conversely, the advanced exergy analysis showed that the plant's mainstream ED rates are endogenous and unavoidable. The component sustainability index (SI) for L1 and L2 ranged between 1.3 ≤ SI ≤ 4.401 and 1.301 ≤ SI ≤ 4.758 , respectively. Similarly, the sustainability results show that the environmental destruction coefficient (EDC) and the environmental destruction index (EDI) were high in L1. Nonetheless, the study identified components with high potential for improvement, making system design and optimization suggestions possible. [ABSTRACT FROM AUTHOR]

Introduction: Endophthalmitis is a serious, sight-threatening purulent inflammation of the intraocular cavities of the eyeball. It greatly affects vision and can lead to severe complications such as panophthalmitis. The prevalence of endophthalmitis varies from one place to another. Aim: To identify the various aetiological and predisposing factors that contribute to endophthalmitis and to assess the visual outcomes following medical intervention (intravitreal antibiotics only) and surgical intervention (both intravitreal antibiotics and pars plana vitrectomy). Materials and Methods: The present study was conducted in the Department of Ophthalmology at Trichy SRM Medical College Hospital and Research Centre, Trichy, Tamil Nadu, India between January 2023 and February 2023. Demographic and clinical data of patients diagnosed with endophthalmitis over a two year period from October 2020 to September 2022 were collected from the Medical Records Department of the Institution for analysis. A total of 50 case records were selected using convenience sampling. Demographic details such as age, gender, predisposing risk factors, visual acuity, microbiological profiles, treatment modalities, and final visual acuity were collected from the present study. Quantitative data was presented as Mean and Standard Deviation (SD), while qualitative data was presented as frequencies and percentages. Summary statistics were analysed using Microsoft Excel version 2018. Results: In present study, 29 (58%) were males and 21 (42%) were females, with the majority falling within the age group of 50-70 years. The mean age of the sample was 53.8±16.1 years. Postoperative causes accounted for 39 (78%) of the cases, with phacoemulsification surgery with foldable intraocular lens implantation being the leading cause in 23 (58.7%) cases. Culture positivity was observed in only 22 (44%) cases, with Staphylococcus (Staph) epidermidis as the major causative organism. The best visual acuity achieved was 6/12 for two patients. Conclusion: Postoperative endophthalmitis remains the most common cause of endophthalmitis. Additionally, patients who presented with better visual acuity had a better visual outcome after treatment. Therefore, patients should be educated about the early signs of endophthalmitis to ensure prompt medical attention and improve visual recovery. [ABSTRACT FROM AUTHOR]

Endogenous endophthalmitis (EE) is an uncommon but potentially devastating ocular infection involving the inner layers of the eye. The global incidence of EE is on the rise. Common ocular signs and symptoms associated with EE include conjunctival injection, ocular pain, and reduced visual acuity. On clinical examination, a history of prior or coexisting systemic infections, symptoms (e.g., fever, malaise), and localizing features may be noted. Clinical diagnosis is often challenging, resulting in critical delays that contribute to a poor prognosis. Blood cultures and ocular fluid samples can aid in conforming causative pathogen(s), after which empirical antibiotic therapy, both systemic and intravitreal, should be instated. The use of steroids to suppress inflammation remains controversial. Surgical options include pars plana vitrectomy. Overall prognosis varies depending on host and pathogen factors, and early diagnosis and initiation of appropriate treatment are crucial. [ABSTRACT FROM AUTHOR]