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Short pulse, multi-path, intersymbol interference, and high sampling rate in UWB communications pose more challenges in system synchronization. This paper proposes three acquisition techniques to synchronize the system at symbol rate sampling. A reference aided match filter is used at the front end to match the incoming data with the pilot codes. An adaptive post detection integration helps to suppress ISI and provides an easy threshold set-up. A bit iteration search assists in reducing acquisition time. Simulation results show a promising acquisition scheme for UWB communication systems at the symbol sampling rate. [ABSTRACT FROM AUTHOR]

This paper presents a fully integrated dual-function filter to be used in a proposed low-cost RF receiver front-end topology that resolved the Narrowband Interference to an ultra-wideband (UWB) receiver. The filter design utilizes high Q passive devices and Q-enhancement technique to provide channel selection in NB operation and NBI rejection in UWB operation. Using NB function for the 802.11a NB, the filter has a tunable gain of 4 to 25dB, a Noise Figure of 8dB and an IIP3 of -47dBm. The operating frequencies are from 5.15 GHz to 5.35 GHz. The input impedance matching is -16dB. Using in the UWB receiver for the frequencies across 3.1 GHz to 9 GHz, the filter has a gain of 0 to 8dB. The filter can reject the NB interference from 5.15 GHz to 5.35 GHz at up to 60dB. The Q of the filter is tunable up to 250 while consuming a maximum of 23.4 mW of power and occupies a die area of 1.1 mm². [ABSTRACT FROM AUTHOR]

Non-transform discontinuity (NTD) is one category of tectonic units along slow- and ultraslow-spreading ridges. Some NTD-related hydrothermal fields that may reflect different driving mechanisms have been documented along slow-spreading ridges, but the discrete survey strategy makes it hard to evaluate the incidence of hydrothermal activity. On ultraslow-spreading ridges, fewer NTD-related hydrothermal activities were reported. Factors contributing to the occurrence of hydrothermal activities at NTDs and whether they could be potential targets for hydrothermal exploration are poorly known. Combining turbidity and oxidation reduction potential (ORP) sensors with a near-bottom camera, Chinese Dayang cruises from 2014 to 2018 have conducted systematic towed surveys for hydrothermal activity around a large NTD along the ultraslow-spreading Southwest Indian Ridge (SWIR, 48.1–48.7° E). Five new potential hydrothermal anomaly sites (2 inferred and 3 suspected) of high or low temperature and the previously inferred Sudi hydrothermal field occurred in diverse morphotectonic settings along a 78 km long ridge axis. The calculated vent frequency (Fs, sites/100 km) was ~7.7 over the entire study area, higher than the modified value (Fs ≈ 6.5) between 48 and 52° E of SWIR. Even only for the 54 km long large NTD, three hydrothermal anomaly sites yielded an Fs of ~5.6, which is higher than that of most ridge sections and is comparable to some fast-spreading ridges with high-resolution surveys. This indicates that NTDs along ultraslow-spreading ridges could be promising areas in fertilizing hydrothermal activities. Moreover, the deeply penetrating faults on the rift valley walls and strain-focused areas may contribute to the formation of NTD-related hydrothermal circulations. We suggest that NTDs along ultraslow-spreading ridges may be potential targets for further exploration of hydrothermal activities and seafloor sulfide deposits.

In this paper, we present a software gain model under random field environment with consideration of not only time to remove faults during in-house testing, cost of removing faults during beta testing, risk cost due to software failure, but also the benefits from reliable executions of the software during the beta testing and filed operation. To our knowledge, this is the first study that incorporates the random filed environmental factor into the cost model. We also provide an optimal release policy in which the net gain of the software development process is maximized. This gain model can help managers and developers to determine when to stop testing the software and release it to beta testing users and to end-users. [ABSTRACT FROM AUTHOR]

Purpose: To obtain a better understanding of the structures around L5 vertebra and provide some anatomical evidence of the feasibility of total en-bloc spondylectomy (TES) on L5 in a posterior-only approach. Methods: 12 simulated TESs on L5 by a posterior-only approach were conducted on human cadavers. The distance between the traction point of L4 nerve root and the dural sac (Da), the anterior-posterior diameter of the vertebral body,(Va), the distance between the start point of L4 nerve root and the traction point of L5 nerve root (Dh) and the height of the vertebral body (Vh) were measured. Paired t-test and liner regression were performed to determine the difference and correlation between Da and Va, and between Dh and Vh. The risk of nerve roots or blood vessels damages, and the obstruction caused by iliac wings were evaluated. Results: Liner correlations were found between Da and Va, and between Dh and Vh. The regression equations were Da = 0.6673Va + 11.28 and Dh = 1.009Vh + 1.003. There are statistical significant differences between Dh and Vh, and between Da and Va in those whose Va

Carbonaceous material (CM) is common in meta-sediments and is generally interpreted to be intimately associated with gold mineralization. For the Bumo deposit in Hainan Province, South China, CM is mainly hosted by greenschist facies—to amphibolite-facies metamophic rocks of the Paleo—to the Mesoproterozoic Baoban Group, and by auriferous veins which could be used as an important gold prospecting indicator. However, the genesis of CM and its relationship with gold mineralization are still unclear. From the field work and thin section observations two types of CM occur, i.e., layered and veinlet. The layered CM occurred in CM-bearing black shales, up to meters thick, and prevails in the deposit. More importantly, Au-bearing sulfides are commonly distributed along the boundary between the quartz veins and layered CM. In contrast, the veinlet CM, co-precipitated with native gold and sulfides, has the thickness of micro- to centi-meters, and these thin veins occur in quartz veins and hydrothermally altered rocks. In addition, layered CM has a stringy shape and laminate structure, while veinlet CM occurs as isometric particles based on the Scanning Electron Microscope (SEM) analysis. The Raman carbonaceous material geothermometer indicates that layered CM with a high maturity is formed at elevated temperatures of 400–550 °C, consistent with X-ray diffraction (XRD) analysis. In contrast, veinlet CM with a low maturity is formed at 200–350 °C and generally consistent with gold mineralization. In addition, layered CM has δ13C values ranging from −30 to −20%, demonstrating a biogenic origin. Consequently, it is interpreted that layered CM is formed by a pre-ore metamorphic event during Caledonian, and its reducing nature promotes gold precipitation via destabilization of aqueous Au complexes or facilitating sulfidation. Veinlet CM is of hydrothermal origin, and its precipitation modified the chemical conditions of ore fluids, leading to the destabilization of Au complexes, which therefore are favorable for mineralization.

Background: Neurogenin2 (Ngn2) is a proneural gene that directs neuronal differentiation of progenitor cells during development. Here, we investigated whether Ngn2 can reprogram MSCs to adopt a neural precursor fate and enhance the therapeutic effects of MSCs after experimental stroke. Methods: In vitro, MSCs were transfected with lenti-GFP or lenti-Ngn2. Following neuronal induction, cells were identified by immunocytochemistry, Western blot and electrophysiological analyses. In a stroke model induced by transient right middle cerebral artery occlusion (MCAO), PBS, GFP-MSCs or Ngn2-MSCs were injected 1 day after MCAO. Behavioral tests, neurological and immunohistochemical assessments were performed. Results: In vitro, Ngn2-MSCs expressed neural stem cells markers (Pax6 and nestin) and lost the potential to differentiate into mesodermal cell types. Following neural induction, Ngn2-MSCs expressed higher levels of neuron-specific proteins MAP2, Tuj1 and NeuN, and also expressed voltage-gated Na+ channel, which was absent in GFP-MSCs. In vivo, after transplantation, Ngn2-MSCs significantly reduced apoptotic cells, decreased infarct volume, and increased the expression of VEGF and BDNF. Finally, Ngn2-MSCs treated animals showed the highest functional recovery among the three groups. Conclusions: Ngn2 was sufficient to convert MSCs into a neural precursor fate and transplantation of Ngn2-MSCs was advantageous for the treatment of stroke rats.

C11H7Co2N3O7, triclinic, P1̅ (no. 2), a = 7.8744(6) Å, b = 9.2561(9) Å, c = 9.6688(9) Å, α = 65.775(9)°, β = 87.625(7)°, γ = 73.654(8)°, V = 614.48(11) Å3, Z = 2, Rgt(F) = 0.0537, wRref(F2) = 0.1458, T = 296 K.

The basic concept of national competitiveness and the analytic potential model for the estimation of countries' competitiveness, such as diamond model of competitive advantages of national economies by M. Porter, the generalized double diamond model of international competitiveness by C. Moon, 9-factors model by S. Cho, Global Competitiveness Index (GCI) and Knowledge Economy Index (KEI) are considered.

Alumina foam ceramics reinforced with alumina fibers were prepared with gel-casting. The effects of the sintering temperature on the foam ceramics were investigated. The foam ceramics were composed of α-Al2O3, C-AlPO4, and T-AlPO4 phases. And the mount of T-AlPO4 phase decreased, while the mount of C-AlPO4 phase increased once the sintering temperature exceeded 1180℃ due to the phase transformation of T-AlPO4 to C-AlPO4 phase. The grain average size of the foam ceramic increased obviously with the sintering temperature rise, so did its bulk density. While its open porosity decreased. The compression strength of the foam ceramic continuously increased with the sintering temperature rise from 980 to 1580 °C.

Background: Iodine is an essential component of thyroid hormones; either low or high intake may lead to thyroid disease. We observed an increase in the prevalence of overt hypothyroidism, subclinical hypothyroidism, and autoimmune thyroiditis with increasing iodine intake in China in cohorts from three regions with different levels of iodine intake: mildly deficient (median urinary iodine excretion, 84 microg per liter), more than adequate (median, 243 microg per liter), and excessive (median, 651 microg per liter). Participants enrolled in a baseline study in 1999, and during the five-year follow-up through 2004, we examined the effect of regional differences in iodine intake on the incidence of thyroid disease. Methods: Of the 3761 unselected subjects who were enrolled at baseline, 3018 (80.2 percent) participated in this follow-up study. Levels of thyroid hormones and thyroid autoantibodies in serum, and iodine in urine, were measured and B-mode ultrasonography of the thyroid was performed at baseline and follow-up. Results: Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the cumulative incidence of overt hypothyroidism was 0.2 percent, 0.5 percent, and 0.3 percent, respectively; that of subclinical hypothyroidism, 0.2 percent, 2.6 percent, and 2.9 percent, respectively; and that of autoimmune thyroiditis, 0.2 percent, 1.0 percent, and 1.3 percent, respectively. Among subjects with euthyroidism and antithyroid antibodies at baseline, the five-year incidence of elevated serum thyrotropin levels was greater among those with more than adequate or excessive iodine intake than among those with mildly deficient iodine intake. A baseline serum thyrotropin level of 1.0 to 1.9 mIU per liter was associated with the lowest subsequent incidence of abnormal thyroid function. Conclusions: More than adequate or excessive iodine intake may lead to hypothyroidism and autoimmune thyroiditis. [ABSTRACT FROM AUTHOR]

Coastal heavy-metal contamination poses significant risks to marine ecosystems and human health, necessitating comprehensive research for effective mitigation strategies. This study assessed heavy-metal pollution in sediments, seawater, and organisms in the Pearl River Estuary (PRE), with a focus on Cd, Cu, Pb, Zn, As, Hg, and Cr. A notable reduction in heavy metal concentrations in surface sediments was observed in 2020 compared to 2017 and 2018, likely due to improved pollution management and COVID-19 pandemic restrictions. Spatial analysis revealed a positive correlation between elevated heavy-metal concentrations (Cu, Pb, Zn, Cd, and As) and areas with significant human activity. Source analysis indicated that anthropogenic activities accounted for 63 % of the heavy metals in sediments, originating from industrial effluents, metal processing, vehicular activities, and fossil fuel combustion. Cd presented a high ecological risk due to its significant enrichment in surface sediments. Organisms in the PRE were found to be relatively enriched with Hg and Cu, with average As concentrations slightly exceeding the Chinese food-health criterion. This study identified high-risk ecological zones and highlighted Cd as the primary pollutant in the PRE. The findings demonstrate the effectiveness of recent pollution control measures and emphasize the need for ongoing monitoring and mitigation to safeguard marine ecosystems and human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Influenza B viruses have cocirculated during most seasonal flu epidemics and can cause significant human morbidity and mortality due to their rapid mutation, emerging drug resistance, and severe impact on vulnerable populations. The influenza B M2 proton channel (BM2) plays an essential role in viral replication, but the mechanisms behind its symmetric proton conductance and the involvement of a second histidine (His27) cluster remain unclear. Here we performed membrane-enabled continuous constant-pH molecular dynamics simulations on wildtype BM2 and a key H27A mutant channel to explore its pH-dependent conformational switch. Simulations captured the activation as the first histidine (His19) protonates and revealed the transition at lower pH values compared to AM2 is a result of electrostatic repulsions between His19 and preprotonated His27. Crucially, we provided an atomic-level understanding of the symmetric proton conduction by identifying preactivating channel hydration in the C-terminal portion. This research advances our understanding of the function of BM2 function and lays the groundwork for further chemically reactive modeling of the explicit proton transport process as well as possible antiflu drug design efforts.

The wide-spreading of multidrug resistance poses a significant threat to human and animal health. Although antimicrobial peptides (AMPs) show great potential application, their instability has severely limited their clinical application. Here, self-assembled AMPs composed of multiple modules based on the principle of associating natural marine peptide N6 with ß-sheet-forming peptide were designed. It is noteworthy that one of the designed peptides, FFN could self-assemble into nanoparticles at 35.46 µM and achieve a dynamic transformation from nanoparticles to nanofibers in the presence of bacteria, resulting in a significant increase in stability in trypsin and tissues by 1.72-57.5 times compared to that of N6. Additionally, FFN exhibits a broad spectrum of antibacterial activity against multidrug-resistant (MDR) gram-positive (G + ) and gram-negative (G - ) bacteria with Minimum inhibitory concentrations (MICs) as low as 2 µM by membrane destruction and complemented by nanofiber capture. In vivo mouse mastitis infection model further confirmed the therapeutic potential and promising biosafety of the self-assembled peptide FFN, which can effectively alleviate mastitis caused by MDR Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and eliminate pathogenic bacteria. In conclusion, the design of peptide-based nanomaterials presents a novel approach for the delivery and clinical translation of AMPs, promoting their application in medicine and animal husbandry., (© 2024. The Author(s).)

Fructose is associated with colorectal cancer tumorigenesis and metastasis through ketohexokinase-mediated metabolism in the colorectal epithelium, yet its role in the tumor immune microenvironment remains largely unknown. Here, we show that a modest amount of fructose, without affecting obesity and associated complications, promotes colorectal cancer tumorigenesis and growth by suppressing the polarization of M1-like macrophages. Fructose inhibits M1-like macrophage polarization independently of fructose-mediated metabolism. Instead, it serves as a signal molecule to promote the interaction between hexokinase 2 and inositol 1,4,5-trisphophate receptor type 3, the predominant Ca 2+ channel on the endoplasmic reticulum. The interaction reduces Ca 2+ levels in cytosol and mitochondria, thereby suppressing the activation of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 1 (STAT1) as well as NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. Consequently, this impedes M1-like macrophage polarization. Our study highlights the critical role of fructose as a signaling molecule that impairs the polarization of M1-like macrophages for tumor growth., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Teratomas are germ cell tumors, commonly affecting ovaries. Teratomas rarely affect extragonadal tissues. Few cases of teratomas occurring in extragonadal tissues have been reported in the past. However, no studies have reported cases of primary teratomas occurring in the broad ligament. In this study, we report a case of a sexually inactive young woman with a 3-day history of lower abdominal pain. B-ultrasound examination revealed an abnormal strong echogenicity mass in the left adnexal area. An exploratory laparotomy was performed on her. The surgery revealed normal size and appearance of both ovaries and uterus. However, a cyst was observed in the left broad ligament, which was diagnosed as benign mature teratoma based on pathology. In this study, we report a rare case of broad ligament teratoma. The clinical data enrich our understanding of teratomas and provide a reference for further studies., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

The noble metal-based hybrid plasmon mode features low loss and strong field localization, making it widely applicable in the field of nanophotonic devices. However, due to the high loss of noble metals, the gain threshold is unacceptably high, usually larger than 0.1 µm -1 . Here we present a hybrid plasmonic waveguide consisting of a SiO 2 layer coated Na nanowire and a hexagonal semiconductor nanowire. Based on the high performance of the proposed waveguide, the Purcell factor exceeding 120 and a confinement factor above 90% are achieved, leading to an ultra-low gain threshold of 0.02117 µm -1 . In addition, the proposed waveguide exhibits an extremely low cross talk, making it highly suitable for applications in compact photonic integrated devices. The proposed waveguide may contribute to the development of low-threshold nano-lasers and promote other applications in nanophotonics.

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in humans and animals. The study aimed to evaluate the efficacy of bLf as an adjuvant combined with AMP (N6) in the treatment of E. coli-induced bacterial enteritis. Sixty female ICR mice were randomly divided into six groups: CK group, NC group:(infected and untreated), N6 treatment group (20 mg/kg), bLf treatment group (100 mg/kg), bLf+ N6-A treatment group (10 mg/kg N6+100 mg/kg bLf) and bLf+N6- b group (20 mg/kg N6+100 mg/kg bLf), the clinical symptoms, intestinal morphology, inflammatory response and serum metabolites were monitored. The results showed that: compared with the NC group, the bLf-N6-A and bLf-N6-B treatment groups had significant reductions in TNF-α and IL-6, significant increases in IL-10, and significant reductions in endotoxin and DAO in plasma (p<0.05). Meanwhile, the bLf-N6-A and bLf-N6-B treatment groups significantly increased the expression of ZO-1, claudin-1 and occludin, increased the height of small intestinal mucosal villi and VH/CD after ETEC K88-induced intestinal injury (p<0.05). The supplementation of bLf and N6 relieved enteritis by balancing intestinal mucosal immunity, improving intestinal morphology and barrier function. BLf combined with N6 can be used as an effective therapeutic strategy for the treatment of bacterial enteritis.

American Oyster Defensin (AOD) is a marine peptide that is derived from North American mussels. It has been demonstrated to exhibit potent antimicrobial activity and high safety in both in vitro and in vivo models. In this study, to facilitate synthesis, mutants of AOD with fewer disulfide bonds were designed and subjected to structural, antimicrobial, and anti-biofilm analysis. The antimicrobial activity of AOD-derived peptides decreased after reduction in the disulfide bond, and among its three derivatives, only AOD-1 inhibited very few bacteria with a MIC value of 64 μg/mL, whereas the others had no inhibitory effect on pathogenic bacteria. The findings demonstrated that full disulfide bonds are indispensable for bactericidal activity, with the α-helix playing a pivotal role in inhibiting bacterial membranes. Furthermore, the results of the ATP, ROS, membrane potential, and membrane fluidity assays demonstrated that intracellular ATP, reactive oxygen species, and membrane fluidity were all increased, while membrane potential was reduced. This indicated that AOD resulted in the impairment of membrane fluidity and induced metabolic disorders, ultimately leading to bacterial death. The inhibitory effect of AOD on the biofilm of S. epidermidis G-81 was determined through the crystal violet and confocal microscopy. The results demonstrated that AOD exhibited a notable inhibitory impact on the biofilm of S. epidermidis G-81. The minimum biofilm inhibitory concentration of AOD on S. epidermidis G-81 was 16 μg/mL, and the minimum biofilm scavenging concentration was 32 μg/mL, which exhibited superior efficacy compared to that of lincomycin. The inhibitory effect on the primary biofilm was 90.3%, and that on the mature biofilm was 82.85%, with a dose-dependent inhibition effect. Concurrently, AOD cleared intra-biofilm organisms and reduced the number of biofilm-holding bacteria by six orders of magnitude. These data indicate that disulfide bonds are essential to the structure and activity of AOD, and AOD may potentially become an effective dual-action antimicrobial and anti-biofilm agent.

To address challenges in screening for chronic kidney disease (CKD), we devised a deep learning-based CKD screening model named UWF-CKDS. It utilizes ultra-wide-field (UWF) fundus images to predict the presence of CKD. We validated the model with data from 23 tertiary hospitals across China. Retinal vessels and retinal microvascular parameters (RMPs) were extracted to enhance model interpretability, which revealed a significant correlation between renal function and RMPs. UWF-CKDS, utilizing UWF images, RMPs, and relevant medical history, can accurately determine CKD status. Importantly, UWF-CKDS exhibited superior performance compared to CTR-CKDS, a model developed using the central region (CTR) cropped from UWF images, underscoring the contribution of the peripheral retina in predicting renal function. The study presents UWF-CKDS as a highly implementable method for large-scale and accurate CKD screening at the population level., (© 2024. The Author(s).)

Terpenoids in plants are mainly synthesized by terpene synthases (TPSs), which play an important role in plant-environment interactions. Gossypium arboreum is one of the important cotton cultivars with excellent pest resistance, however, the biosynthesis of most terpenoids in this plant remains unknown. In this study, we performed a comparative transcriptome analysis of leaves from intact and Helicoverpa armigera-infested cotton plants. The results showed that the H. armigera infestation mainly induced the JA signaling pathway, ten TPS genes were differentially expressed in G. arboreum leaves. Among them, a novel terpene synthase, GaTPS1, was heterologously expressed and functionally characterized in vitro. The enzymatic reaction indicated that recombinant GaTPS1 was primarily responsible for the production of (E)-α-bergamotene. Moreover, molecular docking and site-directed mutagenesis analysis demonstrated that two amino acid residues, A412L and Y535F, distinctly influenced the catalytic activities and product specificity of GaTPS1. The mutants GaTPS1-A412L and GaTPS1-Y535F resulted in a decrease in the proportion of products (E)-α-bergamotene and D-limonene, while an increase in the proportion of products (E)-β-farnesene, α-pinene and β-myrcene. Our findings provide valuable insights into understanding the molecular basis of terpenoid diversity in G. arboreum, with potential applications in plant metabolism regulation and the improvement of resistant cotton cultivars., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Wound infections caused by Staphylococcus aureus often result in localized suppurative lesions that severely impede the healing process, so it is urgent to develop a dress with efficient antimicrobial and pro-healing functions. In this study, the bifunctional injectable hydrogel lactoferrin (Lf)/NZ2114/lithium magnesium silicate hydrogel (LMSH) was first successfully prepared through the electrostatic interaction method. The physical, biological, and efficacy properties are systematically analyzed with good shear-thinning capacity and biocompatibility. More importantly, it inhibits infection and promotes wound healing in a mouse wound infection model after 14 d treatment, and the bactericidal rate and healing rate were over 99.92% and nearly 100%, respectively. Meanwhile, the massive reduction of inflammatory cells, restoration of tissue structure, and angiogenesis in mice showed the anti-inflammatory and pro-healing properties of the hydrogel. The healed wounds showed thickening with more hair follicles and glands, suggesting that the hydrogel Lf/NZ2114/LMSH (Three in One) could be a better dressing candidate for the treatment of S. aureus -induced wound infections.

Background: Myocardial ischemia/reperfusion (I/R) injury is a common pathological process in clinical practice. Developing effective therapeutic strategies to reduce or prevent this injury is crucial. The article aimed to investigate the role and mechanism of mesencephalic astrocyte-derived neurotrophic factor (MANF) and its key subdomains in modulating myocardial I/R-induced cardiomyocyte apoptosis., Methods: MANF stable knockout cell line and MANF mutant overexpression plasmids were constructed. The effects of MANF and mutants on apoptosis and endoplasmic reticulum (ER) stress related proteins were evaluated in hypoxia/reoxygenation-induced HL-1 cardiomyocytes by western blot, immunofluorescence, Tunel and flow cytometry. Echocardiography, ELISA, TTC and Masson were used to observe the effects of recombinant MANF protein (rMANF) on cardiac function in myocardial I/R mice., Results: This study observed increased expression of MANF in both myocardial infarction patients and I/R mice. MANF overexpression in cardiomyocytes decreased ER stress-induced apoptosis, while MANF knockout exacerbated it. rMANF improved cardiac function in I/R mice by reducing injury and inflammation. This study specifically demonstrates that mutations in the α-helix of MANF were more effective in reducing ER stress and cardiomyocyte apoptosis. Mechanistically, MANF and the α-helix mutant attenuated I/R injury by inhibiting the JAK1/STAT1/NF-κB signaling pathway in addition to reducing ER stress-induced apoptosis., Conclusion: These findings highlight MANF and its subdomains as critical regulators of myocardial I/R injury, offering promising therapeutic targets with significant clinical implications for I/R-related diseases., (© 2024. The Author(s).)

Cholecystolithiasis combined with choledocholithiasis represents a prevalent disease. At present, regarding the management of the common bile duct (CBD), T-tube drainage (TTD) and primary duct closure (PDC) emerge as two prominent approaches for biliary tract repair after laparoscopic CBD exploration (LCBDE). Here, retrospective analysis was conducted on the clinical records of 157 patients who underwent LCBDE at our hospital between January 2019 and January 2022. All patients were categorized into the PDC group or the TTD group based on the chosen CBD treatment approach. A comparative assessment was made across demographic factors, preoperative conditions, surgical particulars, and postoperative complications. The results showed that PDC is recommended for patients with a limited number of small stones, particularly when the CBD is in the 10-15 mm diameter range., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Objectives: This study aims to assess the current state of advanced pediatric emergency medicine (PEM) point-of-care ultrasound (POCUS) training in North America, including trends in dedicated PEM POCUS fellowships and alternative advanced POCUS training pathways, to better guide future educational efforts within the field., Methods: We identified and surveyed 22 PEM POCUS fellowship directors across the United States and Canada regarding PEM POCUS fellowship application trends, potential barriers to pursuing additional POCUS training, and novel training models that meet the needs of the PEM POCUS workforce., Results: The past 5 years have seen a growth in both PEM POCUS fellowship program number and trainee positions available, with a general impression by fellowship directors of a high demand for faculty who have these training credentials. However, there was a discordant drop in fellowship applicants and corresponding match rate in 2022, the cause of which is not clear. A number of programs are offering alternative advanced training options including combined PEM/POCUS fellowships and POCUS tracks within PEM fellowship., Conclusion: As POCUS use within PEM evolves, a growing number of advanced training options are being developed. Understanding the motivations and barriers for pursuing advanced POCUS training can help to shape these options going forward, to ensure the experience incorporated within each model meets the needs of trainees, the needs of PEM divisions, and the future needs of our field., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The immunogenicity and safety of the concomitant administration of recombinant COVID-19 vaccine and quadrivalent inactivated influenza vaccine (Split Virion) (QIIV) in Chinese adults are unclear. In this open-label, randomized controlled trial, participants aged ≥ 18 years were recruited. Eligible healthy adults were randomly assigned (1:1) to receive QIIV at the same time as the first dose of COVID-19 vaccine (simultaneous-group) or 14 days after the second dose of COVID-19 vaccine (non-simultaneous-group). The primary outcome was to compare the difference in immunogenicity of QIIV (H1N1, H3N2, Yamagata, and Victoria) between the two groups. A total of 299 participants were enrolled, 149 in the simultaneous-group and 150 in the non-simultaneous-group. There were no significant differences in geometric mean titer (GMT) [H1N1: 386.4 (95%CI: 299.2-499.0) vs. 497.4 (95%CI: 377.5-655.3); H3N2: 66.9 (95%CI: 56.1-79.8) vs. 81.4 (95%CI: 67.9-97.5); Yamagata: 95.6 (95%CI: 79.0-115.8) vs. 74.3 (95%CI: 58.6-94.0); and Victoria: 48.5 (95%CI: 37.6-62.6) vs. 65.8 (95%CI: 49.0-88.4)] and seroconversion rate (H1N1: 87.5% vs. 90.1%; H3N2: 58.1% vs. 62.0%; Yamagata: 75.0% vs. 64.5%; and Victoria: 55.1% vs. 62.8%) of QIIV antibodies between the simultaneous and non-simultaneous groups. For the seroprotection rate of QIIV antibodies, a higher seroprotection rate of Yamagata antibody was observed only in the simultaneous-group than in the non-simultaneous-group [86.0% vs. 76.0%, p  = .040]. In addition, no significant difference in adverse events was observed between the two groups (14.2% vs. 23.5%, p  = .053). In conclusion, no immune interference or safety concerns were found for concomitant administration of COVID-19 vaccine with QIIV in adults aged ≥ 18 years.

The low activity and yield of antimicrobial peptides (AMPs) are pressing problems. The improvement of activity and yield through modification and heterologous expression, a potential way to solve the problem, is a research hot-pot. In this work, a new plectasin-derived variant L-type AP138 (AP138L-arg26) was constructed for the study of recombination expression and druggablity. As a result, the total protein concentration of AP138L-arg26 was 3.1 mg/mL in Pichia pastoris X-33 supernatant after 5 days of induction expression in a 5-L fermenter. The recombinant peptide AP138L-arg26 has potential antibacterial activity against selected standard and clinical Gram-positive bacteria (G + , minimum inhibitory concentration (MIC) 2-16 µg/mL) and high stability under different conditions (temperature, pH, ion concentration) and 2 × MIC of AP138L-arg26 could rapidly kill Staphylococcus aureus (S. aureus) (> 99.99%) within 1.5 h. It showed a high safety in vivo and in vivo and a long post-antibiotic effect (PAE, 1.91 h) compared with vancomycin (1.2 h). Furthermore, the bactericidal mechanism was revealed from two dimensions related to its disruption of the cell membrane resulting in intracellular potassium leakage (2.5-fold higher than control), and an increase in intracellular adenosine triphosphate (ATP), and reactive oxygen species (ROS), the decrease of lactate dehydrogenase (LDH) and further intervening metabolism in S. aureus. These results indicate that AP138L-arg26 as a new peptide candidate could be used for more in-depth development in the future. KEY POINTS: • The AP138L-arg26 was expressed in the P. pastoris expression system with high yield • The AP138 L-arg26 showed high stability and safety in vitro and in vivo • The AP138L-arg26 killed S. aureus by affecting cell membranes and metabolism., (© 2024. The Author(s).)

The development of STING inhibitors for the treatment of STING-related inflammatory diseases continues to encounter significant challenges. The activation of STING is a multi-step process that includes binding with cGAMP, self-oligomerization, and translocation from the endoplasmic reticulum to the Golgi apparatus, ultimately inducing the expression of IRF3 and NF-κB-mediated interferons and inflammatory cytokines. It has been demonstrated that disruption of any of these steps can effectively inhibit STING activation. Traditional structure-based drug screening methodologies generally focus on specific binding sites. In this study, a TransformerCPI model based on protein primary sequences and independent of binding sites is employed to identify compounds capable of binding to the STING protein. The natural product Licochalcone D (LicoD) is identified as a potent and selective STING inhibitor. LicoD does not bind to the classical ligand-binding pocket; instead, it covalently modifies the Cys148 residue of STING. This modification inhibits STING oligomerization, consequently suppressing the recruitment of TBK1 and the nuclear translocation of IRF3 and NF-κB. LicoD treatment ameliorates the inflammatory phenotype in Trex1 -1- mice and inhibits the progression of DSS-induced colitis and AOM/DSS-induced colitis-associated colon cancer (CAC). In summary, this study reveals the potential of LicoD in treating STING-driven inflammatory diseases. It also demonstrates the utility of the TransformerCPI model in discovering allosteric compounds beyond the conventional binding pockets., (© 2024. Science China Press.)

Rationale: Understanding the immune mechanisms associated with liver transplantation (LT), particularly the involvement of tissue-resident memory T cells (TRMs), represents a significant challenge. Methods: This study employs a multi-omics approach to analyse liver transplant samples from both human (n = 17) and mouse (n = 16), utilizing single-cell RNA sequencing, bulk RNA sequencing, and immunological techniques. Results: Our findings reveal a comprehensive T cell-centric landscape in LT across human and mouse species, involving 235,116 cells. Notably, we found a substantial increase in CD8 + TRMs within rejected grafts compared to stable ones. The elevated presence of CD8 + TRMs is characterised by a distinct expression profile, featuring upregulation of tissue-residency markers (CD69, CXCR6, CD49A and CD103 +/- ,), immune checkpoints (PD1, CTLA4, and TIGIT), cytotoxic markers (GZMB and IFNG) and proliferative markers (PCNA and TOP2A) during rejection. Furthermore, there is a high expression of transcription factors such as EOMES and RUNX3. Functional assays and analyses of cellular communication underscore the active role of CD8 + TRMs in interacting with other tissue-resident cells, particularly Kupffer cells, especially during rejection episodes. Conclusions: These insights into the distinctive activation and interaction patterns of CD8 + TRMs suggest their potential utility as biomarkers for graft rejection, paving the way for novel therapeutic strategies aimed at enhancing graft tolerance and improving overall transplant outcomes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

In response to growing concerns about public safety and environmental conservation, it is essential to develop a precise identification method for trace explosives. To improve the stability and detection sensitivity of perovskite quantum dots (PQDs) and address the issue of low porosity in traditional polymer-based photonic crystals (PhCs), this study proposed a PQD photoluminescence (PL) enhancement strategy based on the slow light effect of ZIF-8 PhCs for highly sensitive, selective, and convenient detection of 2,4,6-trinitrophenol (TNP). The slow light effect at the photonic band gap edge is the basis of amplifying the PL signal. PhCs were fabricated by the evaporation-induced self-assembly method. The diffraction wavelength overlapping the whole visible region was designed to match the emission wavelength of PQDs. Results showed that PhCs matching the PBG edge with PQDs' emission peak amplified the PL signal 11.3 times, significantly improving sensitivity for trace TNP detection with a limit as low as 2.52 nM. Moreover, there was a 13.3-fold enhancement of PQDs' fluorescence lifetime when the emission wavelength fell in the PBG range. The hydrophobic surface of ZIF-8 PhCs enhanced the PQDs' stability and moisture resistance. Furthermore, the selective quenching mechanism of TNP by the sensor was photoinduced electron transfer (PET) verified by DFT calculations and time-resolved PL decay dynamics measurements. This study demonstrated great potential for manipulating light emission enhancement by PhCs in developing efficient fluorescent sensors for trace environmental pollutant detection.

Quantum Mechanics/Molecular Mechanics (QM/MM) can describe chemical reactions in molecular dynamics (MD) simulations at a much lower cost than ab initio MD. Still, it is prohibitively expensive for many systems of interest because such systems usually require long simulations for sufficient statistical sampling. Additional MM degrees of freedom are often slow and numerous but secondary in interest. Coarse-graining (CG) is well-known to be able to speed up sampling through both reduction in simulation cost and the ability to accelerate the dynamics. Therefore, embedding a QM system in a CG environment can be a promising way of expediting sampling without compromising the information about the QM subsystem. Sinitskiy and Voth first proposed the theory of Quantum Mechanics/Coarse-grained Molecular Mechanics (QM/CG-MM) with a bottom-up CG mapping. Mironenko and Voth subsequently introduced the DFT-QM/CG-MM formalism to couple a Density Functional Theory (DFT) treated QM system and to an apolar environment. Here, we present a more complete theory that addresses MM environments with significant polarity by explicitly accounting for the electrostatic coupling. We demonstrate our QM/CG-MM method with a chloride-methyl chloride S N 2 reaction system in acetone, which is sensitive to solvent polarity. The method accurately recapitulates the potential of mean force for the substitution reaction, and the reaction barrier from the best model agrees with the atomistic simulations within sampling error. These models also have generalizability. In two other reactive systems that they have not been trained on, the QM/CG-MM model still achieves the same level of agreement with the atomistic QM/MM models. Finally, we show that in these examples the speed-up in the sampling is proportional to the acceleration of the rotational dynamics of the solvent in the CG system.