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Background: Cognitive dysfunction, encompassing perioperative psychological distress and cognitive impairment, is a prevalent postoperative complication within the elderly population, and in severe cases, it may lead to dementia. Building upon our prior research that unveiled a connection between postoperative mood fluctuations and cognitive dysfunction with the phosphorylation of P38, this present investigation aims to delve deeper into the involvement of the P38 MAPK/NLRP3 pathway in perioperative neurocognitive disorders (PND) in an abdominal exploratory laparotomy (AEL) aged mice model., Methods: C57BL/6 mice (male, 18-month-old) underwent AEL with 3 % anesthesia. Then, inhibitors targeting P38 MAPK (SB202190, 1 mg/kg) and GSK3β (TWS119, 10 mg/kg) were administered multiple times daily for 7 days post-surgery. The NLRP3-cKO AEL and WT AEL groups only underwent the AEL procedure. Behavioral assessments, including the open field test (OFT), novel object recognition (NOR), force swimming test (FST), and fear conditioning (FC), were initiated on postoperative day 14. Additionally, mice designated for neuroelectrophysiological monitoring had electrodes implanted on day 14 before surgery and underwent novel object recognition while their local field potential (LFP) was concurrently recorded on postoperative day 14. Lastly, after they were euthanasized, pathological analysis and western blot were performed., Results: SB202190, TWS119, and astrocyte-conditional knockout NLRP3 all ameliorated the cognitive impairment behaviors induced by AEL in mice and increased mean theta power during novel location exploration. However, it is worth noting that SB202190 may exacerbate postoperative depressive and anxiety-like behaviors in mice, while TWS119 may induce impulsive behaviors., Conclusions: Our study suggests that anesthesia and surgical procedures induce alterations in mood and cognition, which may be intricately linked to the P38 MAPK/NLRP3 pathway., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Thrombosis and inflammation are primary contributors to the onset and progression of ischemic stroke. The contact-kinin pathway, initiated by plasma kallikrein (PK) and activated factor XII (FXIIa), functions bidirectionally with the coagulation and inflammation cascades, providing a novel target for therapeutic drug development in ischemic stroke. In this study, we identified a bat-derived oligopeptide from Myotis myotis (Borkhausen, 1797), designated LE6 (Leu-Ser-Glu-Glu-Pro-Glu, 702 Da), with considerable potential in stroke therapy due to its effects on the contact kinin pathway. Notably, LE6 demonstrated significant inhibitory effects on PK and FXIIa, with inhibition constants of 43.97 μmol/L and 6.37 μmol/L, respectively. In vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin time. In murine models, LE6 effectively inhibited carrageenan-induced mouse tail thrombosis, FeCl 3 -induced carotid artery thrombosis, and photochemically induced intracerebral thrombosis. Furthermore, LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion models. Notably, the low toxicity, hemolytic activity, and bleeding risk of LE6, along with its synthetic simplicity, underscore its clinical applicability. In conclusion, as an inhibitor of FXIIa and PK, LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.

Cryptococcus neoformans ( C. neoformans ) is a pathogenic fungus that can cause life-threatening meningitis, particularly in individuals with compromised immune systems. The current standard treatment involves the combination of amphotericin B and azole drugs, but this regimen often leads to inevitable toxicity in patients. Therefore, there is an urgent need to develop new antifungal drugs with improved safety profiles. We screened antimicrobial peptides from the hemolymph transcriptome of Blaps rhynchopetera ( B. rhynchopetera ), a folk Chinese medicine. We found an antimicrobial peptide named blap-6 that exhibited potent activity against bacteria and fungi. Blap-6 is composed of 17 amino acids (KRCRFRIYRWGFPRRRF), and it has excellent antifungal activity against C. neoformans , with a minimum inhibitory concentration (MIC) of 0.81 μM. Blap-6 exhibits strong antifungal kinetic characteristics. Mechanistic studies revealed that blap-6 exerts its antifungal activity by penetrating and disrupting the integrity of the fungal cell membrane. In addition to its direct antifungal effect, blap-6 showed strong biofilm inhibition and scavenging activity. Notably, the peptide exhibited low hemolytic and cytotoxicity to human cells and may be a potential candidate antimicrobial drug for fungal infection caused by C. neoformans .

Drug resistance against bacteria and fungi has become common in recent years, and it is urgent to discover novel antimicrobial peptides to manage this problem. Many antimicrobial peptides from insects have been reported to have antifungal activity and are candidate molecules in the treatment of human diseases. In the present study, we characterized an antifungal peptide named blapstin that was isolated from the Chinese medicinal beetle Blaps rhynchopetera used in folk medicine. The complete coding sequence was cloned from the cDNA library prepared from the midgut of B. rhynchopetera . It is a 41-amino-acid diapause-specific peptide (DSP)-like peptide stabilized by three disulfide bridges and shows antifungal activity against Candida albicans and Trichophyton rubrum with MICs of 7 μM and 5.3 μM, respectively. The C. albicans and T. rubrum treated with blapstin showed irregular and shrunken cell membranes. In addition, blapstin inhibited the activity of C. albicans biofilm and showed little hemolytic or toxic activity on human cells and it is highly expressed in the fat body, followed by the hemolymph, midgut, muscle, and defensive glands. These results indicate that blapstin may help insects fight against fungi and showed a potential application in the development of antifungal reagents. IMPORTANCE Candida albicans is one of the conditional pathogenic fungi causing severe nosocomial infections. Trichophyton rubrum and other skin fungi are the main pathogens of superficial cutaneous fungal diseases, especially in children and the elderly. At present, antibiotics such as amphotericin B, ketoconazole, and fluconazole are the main drugs for the clinical treatment of C. albicans and T. rubrum infections. However, these drugs have certain acute toxicity. Long-term use can increase kidney damage and other side effects. Therefore, obtaining broad-spectrum antifungal drugs with high efficiency and low toxicity for the treatment of C. albicans and T. rubrum infections is a top priority. Blapstin is an antifungal peptide which shows activity against C. albicans and T. rubrum. The discovery of blapstin provides a novel clue for our understanding of the innate immunity of Blaps rhynchopetera and provides a template for designing antifungal drugs., Competing Interests: The authors declare no conflict of interest.

A large number of protease inhibitors have been found from leeches, which are essential in various physiological and biological processes. In the curret study, a novel elastase inhibitor was purified and characterized from the leech of Hirudinaria manillensis, which was named HMEI-A. Primary structure analysis showed that HMEI-A belonged to a new family of proteins. HMEI-A exerted inhibitory effects on elastase and showed potent abilities to inhibit elastase with an inhibition constant (K i ) of 1.69 × 10 -8 mol·L -1 . Further study showed that HMEI-A inhibited the formation of neutrophil extracellular trap (NET). These results suggested that HMEI-A from the leech of H. manillensis is a novel elastase inhibitor which can suppress NET formation. It may play a significant role in blood-sucking of leeches and is a potential candidate as an anti-inflammatory agent., (Copyright © 2021 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

The Faraday-effect based polarimeter and interferometer are developed for non-perturbation magnetic field and density measurements on the Keda Reconnection eXperiment (KRX) device. The magnetic reconnection is externally driven by a pair of parallel current plates. To design this instrument and provide an alternative way to facilitate theory-experiment comparisons via forward modeling of the diagnostics process with full plasma dynamics given by simulation, we develop a synthetic diagnostics based on 2D photonic integrated circuit simulation for magnetic reconnection on the KRX. The view-line geometry is optimized and wavelengths (1 mm) of the polarimeter and interferometer are selected to ensure the sensitivity of measurement on the KRX. We have simulated magnetic reconnection on the x-line (x-z plane) with horizontal viewing and vertical viewing for line of sight measurements. It is found that the current sheet width and indicator of magnetic reconnection can be inferred directly from the dynamics of Faraday rotation even with the line-integrated character of polarimeter-interferometer diagnostics.

The structural modification of polysaccharides directly affects their physicochemical properties and applications. Dextran, a chained polysaccharide, consists of multiple d-glucose molecules with repetitive structures. In this study, the physicochemical properties of oxidized dextran (DO) at different concentrations of NaClO/NaBr and H 2 O 2 were compared. The results showed that NaClO/NaBr oxidation is more conducive to the formation of carboxyl groups. Oxidized dextran with NaClO/NaBr (DOB) showed good iron (III) chelating ability, and the DOB‑iron (III) complex (DOBIC) had an iron content of 28.31%. According to structural analysis, NaClO/NaBr (2 g/100 g of active chlorine) and H 2 O 2 (4 g/100 g), respectively, oxidize the C1 and C2 hydroxyl groups of dextran to carboxyl groups and open the ring when DO and iron have the strongest chelation ability. The complex is indeed a chelate iron complex, and iron core is composed of iron oxyhydroxide or the β-FeOOH mineral polymorph. These results indicate that DOBIC is expected to be a good iron supplement or food additive to strengthen iron., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Immunoglobulin A nephropathy (IgAN) is among the most common primary glomerular diseases. The prognosis in IgAN is affected by dyslipidemia, a risk factor for cardiovascular disease. The c-Maf inducing protein (CMIP) gene has been found to be associated with lipid metabolism. But the association between the CMIP rs16955379 single nucleotide polymorphism (SNP) and dyslipidemia or the related clinicopathological features in IgAN have not been reported thus far. The present study investigated the correlation between them. The CMIP rs16955379 SNP genotypes of 300 subjects with IgAN recruited from the First Affiliated Hospital of Guangxi Medical University were identified by polymerase chain reaction and direct sequencing. Compared with the control (normal lipid) group, the dyslipidemia group with IgAN had higher blood uric acid, serum creatinine, blood urea nitrogen and urinary protein quantity, higher proportions of mesangial cell proliferation and renal tubular atrophy/interstitial fibrosis (IFTA), and a lower estimated glomerular filtration rate and serum albumin. The frequencies of the CMIP rs16955379 SNP TT genotype and T allele in the dyslipidemia group were higher than in the control group. Triglyceride, apolipoprotein A1 (ApoA1), ApoA1/B, incidences of mesangial cell proliferation, and IFTA were higher in TT genotype carriers than in CC/CT genotype carriers. Serum lipid profiles and dyslipidemia were significantly associated with renal dysfunction and IFTA. IgAN patients with the TT genotype were more likely to have dyslipidemia, renal dysfunction and IFTA (P < 0.05 for all above). These results indicate that CMIP rs16955379 SNP may be a genetic susceptibility gene for dyslipidemia and poor renal outcome in IgAN., Competing Interests: None., (IJCEP Copyright © 2018.)

Objectives: To test whether myocardial apoptosis can be induced by traumatic fracture of lower limbs with hemorrhage, in order to lay a foundation of myocardial injury after traumatic fracture for the follow-up study., Methods: Twenty SD rats were randomly divided into two groups, i. e. control group and trauma group( n =10). A rat model of traumatic hemorrhage was establish, and a traumatic model of the original generation of myocardial cell culture was constructed in vitro . The level of interleukin-2(IL-2),IL-6,IL-10 and tumor necrosis factor-α(TNF-α) in rat serum was detected by ELISA at 0, 1, 2, 4, 8, 12, 16, 24 and 48 hour to find the most significant point. The pathological cardiac injury in rats was observed by HE staining under a microscope, and the apoptosis of cultured cardiomyocyte in vitro was detected by TUNEL methods. The expressions of apoptosis gene,(Bcl-2) and Bax, in myocardium of rat and cultured cardiomyocyte in vitro were detected by Western blot and RT-PCR., Results: At the 4 th hour after trauma, IL-6 and IL-10 in the serum of rats reached its highest, IL-2 reached its lowest at the 8th hour after trauma, and TNF-αreached its highest at 1 hour after trauma, then all recovered to their normol level gradually. Myocardial HE staining indicated that cardiomyocyte was swelling, disordered derangement, inflammatory cell infiltrated; a large number of myocardial cell nuclei was dyedbrown in TUNEL test which proved that the apoptosis index increased ( P <0.05). Western blot and RT-PCR results showed that the expression of pro-apoptotic gene Bax was up-regulated ( P <0. 05), while expression of anti apoptosis gene Bcl-2 down-regulated ( P <0.05)., Conclusions: The myocardial apoptosis can be induced by traumatic fracture of lower limbs with hemorrhage in rats, and then lead to myocardial injury.

Background: The relationship between allergic disease and irritable bowel syndrome (IBS) is poorly understood. We aimed to investigate the potential association as well as the underlying immunological mechanisms., Methods: A retrospective case-control study of 108 atopic patients from among outpatients in an allergy clinic (allergic rhinitis [AR], n = 49; chronic urticaria [CU], n = 59) and 74 controls from among ward companions was conducted from November 2016 to March 2017. The detection rates and related gastrointestinal (GI) symptoms of IBS, as well as immunological indices, were calculated., Results: CU patients had a trend of increase in the detection of IBS compared to controls (OR = 4.846; 95% CI 0.967-24.279, p = 0.077). Loose stools (OR = 2.406; 95% CI 1.075-5.386, p < 0.05) and viscous stools (OR = 2.665; 95% CI 1.250-5.682, p < 0.05) were more common in CU patients. Atopic patients positive for serum total immunoglobulin E (IgE) (OR = 3.379; 95% CI 1.088-10.498, p < 0.05) or house dust mite (HDM)-specific IgE (OR = 3.640; 95% CI 1.228-10.790, p < 0.05) were more likely to have abdominal bloating. Besides, a positive association between levels of total IgE and severity of abdominal bloating was observed (p < 0.05). An HDM-specific IgE-positive reaction was independently associated with abdominal bloating in atopic patients (p < 0.05)., Conclusions: Allergic disease has a clear clinical association with IBS with more frequent and severe symptoms of IBS. CU patients have a tendency to suffer from IBS, usually with diarrhea. Serum total IgE and HDM-specific IgE are positively correlated with GI symptoms in atopic patients., (© 2018 S. Karger AG, Basel.)

This paper extends on previous research on the extraction and statistical analysis on relevant dynamic features (width, grayscale and radian combined with writing sequence information) in forensic handwriting examinations. In this paper, a larger signature database was gathered, including genuine signatures, freehand imitation signatures, random forgeries and tracing imitation signatures, which are often encountered in casework. After applying Principle Component Analysis (PCA) of the variables describing the proximity between specimens, a two-dimensional kernel density estimation was used to describe the variability of within-genuine comparisons and genuine-forgery comparisons. We show that the overlap between the within-genuine comparisons and the genuine-forgery comparisons depends on the imitated writer and on the forger as well. Then, in order to simulate casework conditions, cases were simulated by random sampling based on the collected signature dataset. Three-dimensional normal density estimation was used to estimate the numerator and denominator probability distribution used to compute a likelihood ratio (LR). The comparisons between the performance of the systems in SigComp2011 (based on static features) and the method presented in this paper (based on relevant dynamic features) showed that relevant dynamic features are better than static features in terms of accuracy, false acceptance rate, false rejection rate and calibration of likelihood ratios., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Long-distance entanglement distribution is essential for both foundational tests of quantum physics and scalable quantum networks. Owing to channel loss, however, the previously achieved distance was limited to ~100 kilometers. Here we demonstrate satellite-based distribution of entangled photon pairs to two locations separated by 1203 kilometers on Earth, through two satellite-to-ground downlinks with a summed length varying from 1600 to 2400 kilometers. We observed a survival of two-photon entanglement and a violation of Bell inequality by 2.37 ± 0.09 under strict Einstein locality conditions. The obtained effective link efficiency is orders of magnitude higher than that of the direct bidirectional transmission of the two photons through telecommunication fibers., (Copyright © 2017, American Association for the Advancement of Science.)

It is hypothesized that protease inhibitors play an essential role in survival of venomous animals through protecting peptide/protein toxins from degradation by proteases in their prey or predators. However, the biological function of protease inhibitors in scorpion venoms remains unknown. In the present study, a trypsin inhibitor was purified and characterized from the venom of scorpion Mesobuthus eupeus, which enhanced the biological activities of crude venom components in mice when injected in combination with crude venom. This protease inhibitor, named MeKTT-1, belonged to Kunitz-type toxins subfamily. Native MeKTT-1 selectively inhibited trypsin with a Kivalue of 130 nmol·L(-1). Furthermore, MeKTT-1 was shown to be a thermo-stable peptide. In animal behavioral tests, MeKTT-1 prolonged the pain behavior induced by scorpion crude venom, suggesting that protease inhibitors in scorpion venom inhibited proteases and protect the functionally important peptide/protein toxins from degradation, consequently keeping them active longer. In conclusion, this was the first experimental evidence about the natural existence of serine protease inhibitor in the venom of scorpion Mesobuthus eupeus, which preserved the activity of venom components, suggests that scorpions may use protease inhibitors for survival., (Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Aim: To explore Chinese physicians' perceptions towards fecal microbiota transplantation (FMT) and to provide information and an assessment of FMT development in China., Methods: A self-administered questionnaire was developed according to the FMT practice guidelines and was distributed to physicians in hospitals via Internet Research Electronic Data Capture (REDcap) software and electronic mails to assess their attitudes toward and knowledge of FMT. The questionnaire included a brief introduction of FMT that was followed by 20 questions. The participants were required to respond voluntarily, under the condition of anonymity and without compensation. Except for the fill-in-the-blank questions, all of the other questions were required in the REDcap data collection systems, and the emailed questionnaires were completed based on eligibility., Results: Up to December 9, 2014, 844 eligible questionnaires were received out of the 980 distributed questionnaires, with a response rate of 86.1%. Among the participants, 87.3% were from tertiary hospitals, and there were 647 (76.7%) gastroenterologists and 197 (23.3%) physicians in other departments (non-gastroenterologists). Gastroenterologists' awareness of FMT prior to the survey was much higher than non-gastroenterologists' (54.3 vs 16.5%, P < 0.001); however, acceptance of FMT was not statistically different (92.4 vs 87.1%, P = 0.1603). Major concerns of FMT included the following: acceptability to patients (79.2%), absence of guidelines (56.9%), and administration and ethics (46.5%). On the basis of understanding, the FMT indications preferred by physicians were recurrent Clostridium difficile infection (86.7%), inflammatory bowel disease combined with Clostridium difficile infection (78.6%), refractory ulcerative colitis (70.9%), ulcerative colitis (65.4%), Crohn's disease (59.4%), chronic constipation (43.7%), irritable bowel syndrome (39.1%), obesity (28.1%) and type 2 diabetes (23.9%). For donor selection, the majority of physicians preferred individuals with a similar gut flora environment to the recipients. 76.6% of physicians chose lower gastrointestinal tract as the administration approach. 69.2% of physicians considered FMT a safe treatment., Conclusion: Chinese physicians have awareness and a high acceptance of FMT, especially gastroenterologists, which provides the grounds and conditions for the development of this novel treatment in China. Physicians' greatest concerns were patient acceptability and absence of guidelines.

Magnetization measurements have been carried out on a series of carefully prepared single-phase Mn(1+x)Ga (0

Various bio-active substances in amphibian skins play important roles in survival of the amphibians. Many protease inhibitor peptides have been identified from amphibian skins, which are supposed to negatively modulate the activity of proteases to avoid premature degradation or release of skin peptides, or to inhibit extracellular proteases produced by invading bacteria. However, there is no information on the proteinase inhibitors from the frog Lepidobatrachus laevis which is unique in South America. In this work, a cDNA encoding a novel trypsin inhibitor-like (TIL) cysteine-rich peptide was identified from the skin cDNA library of L. laevis. The 240-bp coding region encodes an 80-amino acid residue precursor protein containing 10 half-cysteines. By sequence comparison and signal peptide prediction, the precursor was predicted to release a 55-amino acid mature peptide with amino acid sequence, IRCPKDKIYKFCGSPCPPSCKDLTPNCIAVCKKGCFCRDGTVDNNHGKCVKKENC. The mature peptide was named LL-TIL. LL-TIL shares significant domain similarity with the peptides from the TIL supper family. Antimicrobial and trypsin-inhibitory abilities of recombinant LL-TIL were tested. Recombinant LL-TIL showed no antimicrobial activity, while it had trypsin-inhibiting activity with a Ki of 16.5178 μM. These results suggested there was TIL peptide with proteinase-inhibiting activity in the skin of frog L. laevis. To the best of our knowledge, this is the first report of TIL peptide from frog skin.

As a group of intestinal hormones and neurotransmitters, cholecystokinins (CCKs) regulate and affect pancreatic enzyme secretion, gastrointestinal motility, pain hypersensitivity, digestion and satiety, and generally contain a DYMGWMDFG sequence at the C-terminus. Many CCKs have been reported in mammals. However, only a few have been reported in amphibians, such as Hyla nigrovittata, Xenopus laevis, and Rana catesbeiana, with none reported in urodele amphibians like newts and salamanders. Here, a CCK called CCK-TV was identified and characterized from the skin of the salamander Tylototriton verrucosus. This CCK contained an amino acid sequence of DYMGWMDF-NH2 as seen in other CCKs. A cDNA encoding the CCK precursor containing 129 amino acid residues was cloned from the cDNA library of T. verrucosus skin. The CCK-TV had the potential to induce the contraction of smooth muscle strips isolated from porcine gallbladder, eliciting contraction at a concentration of 5.0 x 10⁻¹¹ mol/L and inducing maximal contraction at a concentration of 2.0 x 10⁻⁶ mol/L. The EC50 was 13.6 nmol/L. To the best of our knowledge, this is the first report to identify the presence of a CCK in an urodele amphibian.