Promoter regulatory mode evolution enhances the high multidrug resistance of tmexCD1-toprJ1.

Antibiotic resistance could rapidly emerge from acquiring the mobile antibiotic resistance genes, which are commonly evolved from an intrinsic gene. The emergence of the plasmid-borne mobilized efflux pump gene cluster tmexCD1-toprJ1 renders the last-resort antibiotic tigecycline ineffective, although its evolutionary mechanism remains unclear. In this study, we investigate the regulatory mechanisms of the progenitor NfxB-MexCD-OprJ, a chromosomally encoded operon that does not mediate antibiotic resistance in the wild-type version, and its homologs, TNfxB1-TMexCD1-TOprJ1 mediating high-level tigecycline resistance, and TNfxB3-TMexCD3-TOprJ1. Mechanistic studies demonstrated that in nfxB-mexCD-oprJ, MexCD expression was under a weaker promoter, PmexC and inhibited by a strong repressor NfxB. For tmexCD1-toprJ1, TMexCD1 was highly expressed owing to the presence of a strong promoter, PtmexC1, and an inactive suppressor, TNfxB1, with a T39R mutation that rendered it unable to bind to promoter DNA. In tnfxB3-tmexCD3-toprJ1b, TMexCD3 expression was intermediate because of the local regulator TNfxB3, which binds to two inverted repeat sequences of PtmexC. Additionally, TNfxB3 exhibited lower protein expression and weaker DNA binding affinity than its ancestor NfxB, together with their promoter activities difference explaining the different expression levels of tmexCD-toprJ homologs. Distinct fitness burdens on these homologs-carrying bacteria were observed due to the corresponding expression level, which might be associated with their global prevalence. In summary, our data depict the mechanisms underlying the evolution and dissemination of an important mobile antibiotic resistance gene from an intrinsic chromosomal gene.IMPORTANCEAs antibiotic resistance seriously challenges global health, tigecycline is one of the few effective drugs in the pipeline against infections caused by multidrug-resistant pathogens. Our previous work identified a novel tigecycline resistance efflux pump gene cluster tmexCD1-toprJ1 in animals and humans, together with its various variants, a rising clinical concern. Herein, this study focused on how the local regulation modes of tmexCD1-toprJ1 evolved to a highly expressed efflux pump. Through comparative analysis between three tnfxB-tmexCD-toprJ homologs and their progenitor nfxB-mexCD-oprJ, modes, we demonstrated the evolutionary dynamics from a chromosomal silent gene to an active state. We found the de-repression of the local regulator and an increase of the promoter activity work together to promote a high production of drug efflux machines and enhance multidrug resistance. Our findings revealed that TMexCD1-TOprJ1 adopts a distinct evolutionary path to achieve higher multidrug resistance, urgently needing tight surveillance.

Tunable non-polarizing optical bandpass filtering in prism pair coupled planar optical waveguide.

A tunable non-polarizing optical bandpass filter structure, comprising a prism pair coupled planar optical waveguide (POW), is demonstrated, by changing the incident angle of the filter. Experimental measurements show that pass bands for both TM and TE polarized waves are present in the filter simultaneously, and the two passbands overlap on each other. The overlapping of the two passbands can be sustainable for the peak wavelength from 623 to 852 nm as the incident angle of the light tuned within 2°. This POW based optical bandpass filter can be potentially applicable in various fields of optical and laser spectroscopies.

Toward Better and Healthier Air Quality: Global PM2.5 and O3 Pollution Status and Risk Assessment Based on the New WHO Air Quality Guidelines for 2021.

To reduce the high burden of disease caused by air pollution, the World Health Organization (WHO) released new Air Quality Guidelines (AQG) on September 22, 2021. In this study, the daily fine particulate matter (PM2.5) and surface ozone (O3) data of 618 cities around the world is collected from 2019 to 2022. Based on the new AQG, the number of attainment days for daily average concentrations of PM2.5 (≤ 15 µg m-3) and O3 (≤ 100 µg m-3) is approximately 10% and 90%, respectively. China and India exhibit a decreasing trend in the number of highly polluted days (> 75 µg m-3) for PM. Every year over 68% and 27% of cities in the world are exposed to harmful PM2.5 (> 35 µg m-3) and O3 (> 100 µg m-3) pollution, respectively. Combined with the United Nations Sustainable Development Goals (SDGs), it is found that more than 35% of the world's cities face PM2.5-O3 compound pollution. Furthermore, the exposure risks in these cities (China, India, etc.) are mainly categorized as "High Risk", "Risk", and "Stabilization". In contrast, economically developed cities are mainly categorized as "High Safety", "Safety", and "Deep Stabilization." These findings indicate that global implementation of the WHO's new AQG will minimize the inequitable exposure risk from air pollution.

Pectic oligosaccharides: enzymatic preparation, structure, bioactivities and application.

Pectic oligosaccharides have become novel bioactive components. However, the comprehensive preparation methods, structural features, bioactivities and application of them lack a systematic review. Here, we focused on the enzymatic preparation of pectic oligosaccharides, and attempted to outline relationships among the enzymolysis condition, structure, bioactivities and application of pectic oligosaccharides. Pectic oligosaccharides were characterized by the oligosaccharides with units of →4)-α-GalpA-(1→4)-α-GalpA-(1→ or →4)-α-GalpA-(1→2)-α-Rhap-(1→. Enzymatic method was the most suitable approach for pectic oligosaccharides preparation that was significantly affected by the enzyme's type, time and concentration. Besides, pectic oligosaccharides possessed various bioactivities including prebiotic, anti-glycosylation, antioxidant, anticancer and lipid metabolism-regulation activities, which were closely associated with the molecular weight, the structure of side chain and the monosaccharide composition. Especially, many pectic oligosaccharides with low molecular weight demonstrated high prebiotic activities, and those with arabinogalactan side chains exhibited strong anticancer activities. Moreover, pectic oligosaccharides have been used in food preservatives, dairy product additives and food processing aids. Nevertheless, the industrial application, novel technology exploration, and structure-bioactivity relationship of pectic oligosaccharides remain a demanding and significant task for future work.

Acidity-Triggered "Sticky Spotlight": CCK2R-Targeted TME-Sensitive NIR Fluorescent Probes for Tumor Imaging In Vivo.

Cancer which causes high mortality globally threatens public health seriously. There is an urgent need to develop tumor-specific near-infrared (NIR) imaging agents to achieve precise diagnosis and guide effective treatment. In recent years, imaging probes that respond to acidic environments such as endosomes, lysosomes, or acidic tumor microenvironments (TMEs) are being developed. However, because of their nonspecific internalization by both normal and tumor cells, resulting in a poor signal-to-noise ratio in diagnosis, these pH-sensitive probes fail to be applied to in vivo tumor imaging. To address this issue, a cholecystokinin-2 receptor (CCK2R)-targeted TME-sensitive NIR fluorescent probe R2SM was synthesized by coupling pH-sensitive heptamethine cyanine with a CCK2R ligand, minigastrin analogue 11 (MG11) for in vivo imaging, in which MG11 would target overexpressed CCK2Rs in gastrointestinal stromal tumors (GISTs). Cell uptake assay demonstrated that R2SM exhibited a high affinity for CCK2R, leading to receptor-mediated internalization and making probes finally accumulated in the lysosomes of tumor cells, which suggested in the tumor tissues, the probes were distributed in the extracellular acidic TME and intracellular lysosomes. With a pKa of 6.83, R2SM can be activated at the acidic TME (pH = 6.5-6.8) and lysosomes (pH = 4.5-5.0), exhibiting an apparent pH-dependent behavior and generating more intense fluorescence in these acidic environments. In vivo imaging showed that coupling of MG11 with a pH-sensitive NIR probe facilitated the accumulation of probe and enhanced the fluorescence in CCK2R-overexpressed HT-29 tumor cells. A high signal was observed in the tumor region within 0.5 h postinjection, indicating its potential application in intraoperative imaging. Fluorescence imaging of R2SM exhibited higher tumor-to-liver and tumor-to-kidney ratios (2.1:1 and 2.3:1, respectively), compared separately with the probes that are lipophilic, pH-insensitive, or MG11-free. In vitro and in vivo studies demonstrated that the synergistic effect of tumor targeting with pH sensitivity plays a vital role in the high signal-to-noise ratio of the NIR imaging probe. Moreover, different kinds of tumor-targeting vectors could be conjugated simultaneously with the NIR dye, which would further improve the receptor affinity and targeting efficiency.

A prognostic model for SARS-CoV-2 breakthrough infection: Analyzing a prospective cellular immunity cohort.

BACKGROUND: Following the COVID-19 pandemic, studies have identified several prevalent characteristics, especially related to lymphocyte subsets. However, limited research is available on the focus of this study, namely, the specific memory cell subsets among individuals who received COVID-19 vaccine boosters and subsequently experienced a SARS-CoV-2 breakthrough infection. METHODS: Flow cytometry (FCM) was employed to investigate the early and longitudinal pattern changes of cellular immunity in patients with SARS-CoV-2 breakthrough infections following COVID-19 vaccine boosters. XGBoost (a machine learning algorithm) was employed to analyze cellular immunity prior to SARS-CoV-2 breakthrough, aiming to establish a prognostic model for SARS-CoV-2 breakthrough infections. RESULTS: Following SARS-CoV-2 breakthrough infection, naïve T cells and TEMRA subsets increased while the percentage of TCM and TEM cells decreased. Naïve and non-switched memory B cells increased while switched and double-negative memory B cells decreased. The XGBoost model achieved an area under the curve (AUC) of 0.78, with an accuracy rate of 81.8 %, a sensitivity of 75 %, and specificity of 85.7 %. TNF-α, CD27-CD19+cells, and TEMRA subsets were identified as high predictors. An increase in TNF-α, cTfh, double-negative memory B cells, IL-6, IL-10, and IFN-γ prior to SARS-CoV-2 infection was associated with enduring clinical symptoms; conversely, an increase in CD3+ T cells, CD4+ T cells, and IL-2 was associated with clinical with non-enduring clinical symptoms. CONCLUSION: SARS-CoV-2 breakthrough infection leads to disturbances in cellular immunity. Assessing cellular immunity prior to breakthrough infection serves as a valuable prognostic tool for SARS-CoV-2 infection, which facilitates clinical decision-making.

Dual contrastive learning for synthesizing unpaired fundus fluorescein angiography from retinal fundus images.

Background: Fundus fluorescein angiography (FFA) is an imaging method used to assess retinal vascular structures by injecting exogenous dye. FFA images provide complementary information to that provided by the widely used color fundus (CF) images. However, the injected dye can cause some adverse side effects, and the method is not suitable for all patients. Methods: To meet the demand for high-quality FFA images in the diagnosis of retinopathy without side effects to patients, this study proposed an unsupervised image synthesis framework based on dual contrastive learning that can synthesize FFA images from unpaired CF images by inferring the effective mappings and avoid the shortcoming of generating blurred pathological features caused by cycle-consistency in conventional approaches. By adding class activation mapping (CAM) to the adaptive layer-instance normalization (AdaLIN) function, the generated images are made more realistic. Additionally, the use of CAM improves the discriminative ability of the model. Further, the Coordinate Attention Block was used for better feature extraction, and it was compared with other attention mechanisms to demonstrate its effectiveness. The synthesized images were quantified by the Fréchet inception distance (FID), kernel inception distance (KID), and learned perceptual image patch similarity (LPIPS). Results: The extensive experimental results showed the proposed approach achieved the best results with the lowest overall average FID of 50.490, the lowest overall average KID of 0.01529, and the lowest overall average LPIPS of 0.245 among all the approaches. Conclusions: When compared with several popular image synthesis approaches, our approach not only produced higher-quality FFA images with clearer vascular structures and pathological features, but also achieved the best FID, KID, and LPIPS scores in the quantitative evaluation.

Microwave hydrothermal sulfuric acid leaching of spent cathode carbon from aluminum electrolysis for high efficiency removal of insoluble calcium fluoride.

Toxic substances, like fluoride salts present in spent cathode carbon (SCC), have been a great risk to the environment and public health. Our approach involves alkali leaching to eliminate soluble fluoride, followed by microwave hydrothermal acid leaching to efficiently remove insoluble CaF2 from SCC. The optimized conditions, including a temperature of 353 K, a solid-liquid ratio of 1:20, and a 60-minute reaction time, resulted in an impressive 95.6 % removal of fluoride from SCC. Various characterization techniques were employed to analyze the composition, micro-morphology, and elemental content of the materials before and after the leaching process. Furthermore, critical process parameters on the leaching separation of insoluble CaF2 during microwave hydrothermal acid leaching were systematically investigated. The study removal mechanism revealed the transformation of insoluble CaF2 in the process of microwave oxidation insertion-hydrothermal acid leaching for SCC. The kinetic characteristics of the two-stage leaching process of CaF2 at different temperatures were analyzed according to the shrinkage kernel model. The results indicate that the two-stage leaching process of CaF2 is affected by mixing control and by diffusion control, severally. The expansion of the graphite flake layer of SCC through oxidative intercalation was identified as a critical process for the thorough removal of CaF2. Microwave hydrothermal acid leaching demonstrated a 17 % improvement over traditional hydrothermal acid leaching within the same reaction time, showcasing a noteworthy enhancement in fluoride removal. Consequently, the microwave oxidizing intercalation-hydrothermal acid leaching treatment of SCC, as explored in this study, offers an effective approach for achieving deep defluoridation of SCC.

Novel Multiplexed High Throughput Screening of Selective Inhibitors for Drug-Metabolizing Enzymes Using Human Hepatocytes.

Selective chemical inhibitors are critical for reaction phenotyping to identify drug-metabolizing enzymes that are involved in the elimination of drug candidates. Although relatively selective inhibitors are available for the major cytochrome P450 enzymes (CYP), they are quite limited for the less common CYPs and non-CYPs. To address this gap, we developed a multiplexed high throughput screening (HTS) assay using 20 substrate reactions of multiple enzymes to simultaneously monitor the inhibition of enzymes in a 384-well format. Four 384-well assay plates can be run at the same time to maximize throughput. This is the first multiplexed HTS assay for drug-metabolizing enzymes reported. The HTS assay is technologically enabled with state-of-the-art robotic systems and highly sensitive modern LC-MS/MS instrumentation. Virtual screening is utilized to identify inhibitors for HTS based on known inhibitors and enzyme structures. Screening of ~4600 compounds generated many hits for many drug-metabolizing enzymes including the two time-dependent and selective aldehyde oxidase inhibitors, erlotinib and dibenzothiophene. The hit rate is much higher than that for the traditional HTS for biological targets due to the promiscuous nature of the drug-metabolizing enzymes and the biased compound selection process. Future efforts will focus on using this method to identify selective inhibitors for enzymes that do not currently have quality hits and thoroughly characterizing the newly identified selective inhibitors from our screen. We encourage colleagues from other organizations to explore their proprietary libraries using a similar approach to identify better inhibitors that can be used across the industry.

HRD-Net: High resolution segmentation network with adaptive learning ability of retinal vessel features.

Retinal segmentation is a crucial step in the early warning of human health conditions. However, retinal blood vessels possess complex curvature, irregular distribution, and contain multi-scale fine structures, which make the limited receptive field of regular convolution challenging to process their vascular details efficiently. Additionally, the encoder-decoder based network leads to irreversible spatial information loss because of multiple downsampling, resulting in over-segmentation and missed segmentation of the vessels. For this reason, we develop a high-resolution network based on Deformable Convolution v3, called HRD-Net. By constructing a high-resolution representation, the network allows special attention to be paid to the details of tiny blood vessels. The proposed feature enhancement cascade module based on Deformable Convolution v3 can flexibly adapt and capture the ever-changing morphology and intricate connections of retinal blood vessels, ensuring the continuity of vessel segmentation. In the output phase of the network, the proposed global aggregation module integrates full-resolution feature maps while suppressing redundant features, achieving an effective fusion of high-level semantic information and spatial detail information. In addition, we have re-examined the selection criteria for activation and normalization methods, and also refine the network architectures from a spatial domain perspective to release redundant computational loads. Testing on the DRIVE, STARE, and CHASE_DB1 datasets indicates that HRD-Net, with fewer parameters, outperforms existing segmentation methods on several evaluation metrics such as F1, ACC, SE, SP, AUC, and IOU.

Rapid screening of the novel bioactive peptides with notable α-glucosidase inhibitory activity by UF-LC-MS/MS combined with three-AI-tool from black beans.

This work aimed to propose a rapid method to screen the bioactive peptides with anti-α-glucosidase activity instead of traditional multiple laborious purification and identification procedures. 242 peptides binding to α-glycosidase were quickly screened and identified by bio-affinity ultrafiltration combined with LC-MS/MS from the double enzymatic hydrolysate of black beans. Top three peptides with notable anti-α-glucosidase activity, NNNPFKF, RADLPGVK and FLKEAFGV were further rapidly screened and ranked by the three artificial intelligence tools (three-AI-tool) BIOPEP database, PeptideRanker and molecular docking from the 242 peptides. Their IC50 values were in order as 4.20 ± 0.11 mg/mL, 2.83 ± 0.03 mg/mL, 1.32 ± 0.09 mg/mL, which was opposite to AI ranking, for the hydrophobicity index of the peptides was not included in the screening criteria. According to the kinetics, FT-IR, CD and ITC analyses, the binding of the three peptides to α-glucosidase is a spontaneous and irreversible endothermic reaction that results from hydrogen bonds and hydrophobic interactions, which mainly changes the α-helix structure of α-glucosidase. The peptide-activity can be evaluated vividly by AFM in vitro. In vivo, the screened FLKEAFGV and RADLPGVK can lower blood sugar levels as effectively as acarbose, they are expected to be an alternative to synthetic drugs for the treatment of Type 2 diabetes.

Spatiotemporal patterns of surface ozone exposure inequality in China.

Rising surface ozone (O3) levels in China are increasingly emphasizing the potential threats to public health, ecological balance, and economic sustainability. Using a 1 km × 1 km dataset of O3 concentrations, this research employs subpopulation demographic data combined with a population-weighted quality model. Its aim is to evaluate quantitatively the differences in O3 exposure among various subpopulations within China, both at a provincial and urban cluster level. Additionally, an exposure disparity indicator was devised to establish unambiguous exposure risks among significant urban agglomerations at varying O3 concentration levels. The findings reveal that as of 2018, the population-weighted average concentration of O3 for all subgroups has experienced a significant uptick, surpassing the average O3 concentration (118 µg/m3). Notably, the middle-aged demographic exhibited the highest O3 exposure level at 135.7 µg/m3, which is significantly elevated compared to other age brackets. Concurrently, there exists a prominent positive correlation between educational attainment and O3 exposure levels, with the medium-income bracket showing the greatest susceptibility to O3 exposure risks. From an industrial vantage point, the secondary sector demographic is the most adversely impacted by O3 exposure. In terms of urban-rural structure, urban groups in all regions had higher levels of exposure to O3 than rural areas, with North and East China having the most significant levels of exposure. These findings not only emphasize the intricate interplay between public health and environmental justice but further highlight the indispensability of segmented subgroup strategies in environmental health risk assessment. Moreover, this research furnishes invaluable scientific groundwork for crafting targeted public health interventions and sustainable air quality management policies.

Segmental femoral fracture malunion: evidence and prognostic analysis of medical intervention in the third century BC.

We examined the remains of an individual who was unearthed from the Tuchengzi site and was believed to be from the Warring States period in China. The remains exhibited segmental femoral fracture. We aimed to deduce the cause of fracture, medical interventions, healing process, and motion behavior after fracture healing using several techniques, including macroscopic observation, computed tomography (CT), and finite element analysis. Based on the morphology of the long bones, it appeared that the individual was male. The fractures resulted in an adduction angle of 5.47° and an anterior flexion angle of 21.34° in the proximal femur, while the femoral neck anteversion angle had been replaced by a retroversion angle of 10.74°. Additionally, the distal femur formed an abnormal anterior convex angle of 144.60°. CT revealed mature callus formation and visible trabecular bundles. The finite element analysis indicated that the maximum von Mises stress in the femur was 17.44 MPa during standing and 96.46 MPa during walking. We suggest that medical practitioners in the Warring States period possessed a good knowledge of thigh anatomy, enabling them to perform fracture reduction and fixation. Reasonable medical intervention facilitated fracture healing and load recovery. Satisfactory fracture healing ensured that the individual could engage in normal standing and walking activities after rehabilitation.

Application of Neo-Pancreaticogastrostomy in Total Laparoscopic Pancreaticoduodenectomy.

Objective: To introduce laparoscopic neo-pancreaticogastrostomy (neo-PG) and investigate its application potential in total laparoscopic pancreaticoduodenectomy (TLPD). Materials and Methods: We performed a single-center prospective single-arm trial to evaluate the feasibility and safety of neo-PG for its initial application in TLPD. The first 50 patients who were operated by a single surgeon and who underwent TLPD with neo-PG at our institution were recruited. The pre/intra/postoperation data were collected and analyzed. Results: Twenty-nine male patients and 21 female patients from May 2022 to March 2023 were included. The mean operation time was 272.60 ± 47.30 minutes. The median PG time was 16 (15, 23) minutes. Six patients had delayed gastric emptying (DGE), and all underwent standard LPD. None of the patients had Grade B/C postoperative pancreatic fistula (POPF) or postoperative hemorrhage, or underwent reoperation. The median length of post-LPD hospital stay was 6 (6, 8) days. None of the patients died within 90 days after surgery. Nineteen cases were pathologically classified as pancreatic lesion, 6 cases as bile duct lesion, 18 cases as duodenal lesion, and 7 cases as ampullary lesion. Conclusion: The laparoscopic neo-PG is a simple, safe, and feasible pancreatic anastomosis that can be applied in TLPD. Pylorus-preserving LPD may decrease DGE rate. Further studies involving more surgeons are warranted to prove that our new technique may terminate POPF in TLPD.

Emergence of tet(X4)-positive Enterobacterales in retail eggs and the widespread of IncFIA(HI1)-HI1A-HI1B(R27) plasmids carrying tet(X4).

The proliferation of antimicrobial-resistant microbes and resistance genes in various foods poses a serious hazard to public health. The plasmid-mediated tigecycline resistance gene tet(X4) has been detected in Enterobacterales from various niches but has not yet been reported in eggs. This study aimed to investigate the occurrence and characteristics of tigecycline-resistant strains from retail eggs. A total of 144 eggs were purchased from farmers' markets in Guangdong province, China, and eggshell (n = 144) and egg content (n = 96) samples were used to screen for tigecycline-resistant strains. Eight Escherichia coli strains (two ST195, one ST48, ST8165, ST752, ST93, ST189, and ST224) and one Klebsiella pneumoniae strain (ST252) recovered from eight (5.56 %, 8/144) egg samples (eggshells, n = 6; egg content, n = 2) were positive for tet(X4). Notably, the two E. coli ST195 strains were closely (15-54 SNPs) related to all the tet(X4)-positive E. coli ST195 from various origins (food animals, foods, migratory birds, human, and environment) deposited in GenBank. The E. coli ST224 showed a close phylogenetic relationship (9-12 SNPs) with two tet(X4)-positive E. coli strains from chicken feces and retail chicken in Guangdong province. The hybrid plasmid IncFIA(HI1)-HI1A-HI1B(R27) constitutes the predominant tet(X4) vector both herein (7/9, 77.78 %) and in the GenBank database (32/160, 20 %). The tet(X4)-positive IncFIA(HI1)-HI1A-HI1B(R27) plasmids, sharing highly similar structures, have been widely disseminated across China. However, the IncFIA(HI1)-HI1A-HI1B(R27) plasmids exhibit poor stability and low conjugation frequency. The contamination of tet(X4)-positive bacteria internally and externally in retail eggs poses a prospective food safety threat. More attention should be paid to the spread of the tet(X4) gene via epidemic clone E. coli ST195 and the plasmid IncFIA(HI1)-HI1A-HI1B(R27).

High-pressure microfluidization enhanced the stability of sodium caseinate-EGCG complex-stabilized fish oil emulsion.

Improving the emulsion-stabilizing effect of protein by chemical or physical modification has been paid much attention recently. Here, sodium caseinate (CS) was treated by high-pressure-microfluidization (HPM) under 0-100 MPa, and was further complexed with (-)-epigallocatechin-3-gallate (EGCG) to form an excellent emulsifier that stabilized fish oil emulsions. Results showed that HPM treatment (especially 80 MPa) significantly changed the secondary structure of CS, and 80 MPa-PCS-EGCG had the best emulsifying and antioxidant activities. In addition, after HPM treatment and EGCG bonding, CS formed a thicker interface layer on the surface of oil droplets, which could better protect the fish oil from the influence by oxygen, temperature and ion concentration. Moreover, the fish oil emulsion stabilized by PCS-EGCG complex significantly delayed the release of free fatty acids subjected to in vitro digestion. Conclusively, HPM-treated CS-EGCG complex could be a potential emulsifier to improve the stability of fish oil emulsions.

Emergence of plasmid-mediated high-level tigecycline resistance gene tet(X4) in Enterobacterales from retail aquatic products.

The spread of antimicrobial-resistant microbes and genes in various foods poses a significant threat to public health. Of particular global concern is the plasmid-mediated tigecycline resistance gene tet(X4), which, while identified in various sources, has not hitherto been reported in aquatic products. This study aimed to investigate the occurrence and characterization of tigecycline-resistant strains from aquatic products. A total of 73 nonrepetitive seafood samples were purchased from 26 farmers' markets to detect tigecycline-resistant strains. Of these, nine Escherichia coli strains (comprising two ST58, one ST195, ST10, ST48, ST88, ST877, ST1244, ST14462) and one Citrobacter meridianamericanus, recovered from nine (12.33 %, 9/73) seafood samples (fish, n = 7; shrimp, clam and crab, n = 1 respectively), were positive for the tet(X4). Notably, phylogenetic analysis showed that E. coli ST195, a common ST carrying tet(X4), has a close phylogenetic relationship (23∼48 SNPs) with 32 tet(X4)-harboring E. coli ST195 isolates (isolated from pigs, animal foods, vegetable, and humans) deposited in NCBI database. Additionally, E. coli ST58 was closely (2 SNPs) related to one tet(X4)-positive E. coli strain from retail vegetables documented in the NCBI database. Whole genome sequencing and bioinformatic analysis revealed that tet(X4) genes were located on IncX1 (7 E. coli) or hybrid plasmid IncFIA(HI1)/IncHI1B(R27)/IncHI1A (2 E.coli and one C. meridianamericanus). These plasmids displayed high homology with those of plasmids from other sources deposited in GenBank database. These findings underscore the role of epidemic clones and plasmids in driving the dissemination of tet(X4) gene within Enterobacterales of aquatic products origin. To the best of our knowledge, this is the first report of tet(X4)-positive Enterobacterales from aquatic products. The pervasive propagation of tet(X4) gene facilitated by epidemic plasmids and clones across food animals, food products, humans, and the environment presents a serious threat to public health.

MyD88 signaling pathways: role in breast cancer.

MyD88 plays a central role in breast cancer, exerting a multitude of effects that carry substantial implications. Elevated MyD88 expression is closely associated with aggressive tumor characteristics, suggesting its potential as a valuable prognostic marker and therapeutic target. MyD88 exerts influence over several critical aspects of breast cancer, including metastasis, recurrence, drug resistance, and the regulation of cancer stem cell properties. Furthermore, MyD88 modulates the release of inflammatory and chemotactic factors, thereby shaping the tumor's immune microenvironment. Its role in immune response modulation underscores its potential in influencing the dynamic interplay between tumors and the immune system. MyD88 primarily exerts intricate effects on tumor progression through pathways such as Phosphoinositide 3-kinases/Protein kinase B (PI3K/Akt), Toll-like Receptor/Nuclear Factor Kappa B (TLR/NF-κB), and others. Nevertheless, in-depth research is essential to unveil the precise mechanisms underlying the diverse roles of MyD88 in breast cancer. The translation of these findings into clinical applications holds great promise for advancing precision medicine approaches for breast cancer patients, ultimately enhancing prognosis and enabling the development of more effective therapeutic strategies.

Effect of a collagen peptide-fish oil high internal phase emulsion on the printability and gelation of 3D-printed surimi gel inks.

The effect of a high internal phase emulsion (HIPE) on three-dimensional-printed surimi gel inks was studied. Increasing the concentration of collagen peptide decreased the particle size of HIPE droplets and improved the viscoelasticity and stability. For example, when the collagen peptide concentration was 5 wt%, the viscoelasticity of the HIPE was high, as indicated by the presence of small and uniform particles, which formed a monolayer in the outer layer of the oil droplets to form stable a HIPE. A HIPE was used as the filling material to fill the surimi gel network, which reduced the porosity of the network. Surimi protein and peptides have dual emulsifying effects on the stabilization of oil. After adding the emulsion, the texture, gel properties and rheological properties of the surimi were reduced, and its printing adaptability was improved. This study provides new ideas for the production of surimi and its application in 3D printing.

Electro-acupuncture inhibits HDAC2 via modulating gut microbiota to ameliorate SNI-induced pain and depression-like behavior in rats.

BACKGROUND: Depression and chronic pain frequent co-occur, exacerbating each other's symptoms and hindering treatment. Emerging studies have highlighted abnormal gut microbiota in both conditions. Previous studies have demonstrated the clinical effectiveness of electro-acupuncture (EA) in managing these conditions, yet the underlying mechanisms remain elusive. METHODS: Spared nerve injury (SNI) was employed to induce chronic pain and depression-like behavior. Rats were randomly assigned to sham SNI (SS), SNI, and EA groups. SNI surgery was performed on all rats, except those in SS group, which underwent sham SNI surgery. Then EA group received 5 weeks of EA treatment. Pain and depression-like behavior were assessed through paw withdrawal threshold, sucrose-preference test, and forced swim test. Gut microbiota composition was analyzed via 16S rDNA sequencing. Brain-Derived Neurotrophic Factor (BDNF) and acetylation-related proteins in the medial prefrontal cortex (mPFC) were evaluated through enzyme-linked immunosorbent assay and western blot. RESULTS: EA treatment significantly ameliorated pain and depression-like behavior. The 16S rDNA sequencing showed EA modulated gut microbiota composition, increased short-chain fatty acids (SCFAs)-producing bacteria, including Akkermansi, Ruminococcaceae and Lachnospiraceae family, particularly Akkermansia. Furthermore, EA increased BDNF, AcH3 and decreased HDAC2 in mPFC. Notably, SCFAs-producing bacteria exhibited a negative correlation with HDAC2 levels. LIMITATIONS: This study exclusively investigated microbiota differences resulting from EA stimulation, without delving into the functional variations brought about by these microbial distinctions. CONCLUSIONS: The therapeutic effects of EA on the comorbidity of chronic pain and depression may involve the modulation of the gut microbiota, resulting in histone acetylation changes and upregulation of BDNF.