CD39 expression defines exhausted CD4+ T cells associated with poor survival and immune evasion in human gastric cancer.

Objectives: CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC-infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results: In comparison with CD4+ T cells from the non-tumor tissues, significantly more GC-infiltrating CD4+ T cells expressed CD39. Most GC-infiltrating CD39+CD4+ T cells exhibited CD45RA-CCR7- effector-memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39-CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion: Our study demonstrates that CD39 expression defines GC-infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.

[Research progress of novel functional materials in extraction of algal toxins].

Algal toxins are secondary metabolites produced by harmful algae; these metabolites are characterized with strong toxicity, diverse structure and bioaccumulation. Aquatic organisms that feed on harmful algae can accumulate algal toxins in their bodies, and the consumption of these organisms by humans can cause symptoms of paralysis, diarrhea, and even death. The onset of poisoning can occur within as little as 30 min; in many cases, no suitable antidote for algal toxins is available. Thus, algal toxins present significant threats to human health, the aquaculture industry, and aquatic ecosystems. Because the potential risks of algal toxins are a critical issue, these toxins have become a research hotspot. The water environment and various types of aquatic products should be monitored and analyzed to ensure their safety. However, because of possible matrix effects and the low content of algal toxins in actual samples, an efficient pretreatment method is necessary prior to instrumental analyses. Efficient sample pretreatment techniques can not only reduce or eliminate interferences from the sample matrix during analysis but also enrich the target analytes to meet the detection limit of the analytical instrument, thereby ensuring the sensitivity and accuracy of the detection method. In recent years, sample pretreatment techniques such as solid-phase extraction (SPE), solid-phase microextraction (SPME), magnetic SPE (MSPE), dispersive SPE (DSPE), and pipette tip-based SPE (PT-SPE) have gained wide attention in the field of algal-toxin separation and analysis. The performance of these pretreatment techniques largely depends on the characteristics of the extraction materials. Given the diverse physicochemical properties of algal toxins, including their different molecular sizes, hydrophobicity/hydrophilicity, and charges, the design and preparation of materials suitable for algal-toxin extraction is an essential undertaking. The optimal extraction material should be capable of reversible algal-toxin adsorption and preferably possess a porous structure with a large surface area to allow for high recovery rates and good interfacial contact with the toxins. Additionally, the extraction material should exhibit good chemical stability in the sample solution and elution solvent within the working pH range; otherwise, it may dissolve or lose its functional groups. Many research efforts have sought to develop novel adsorbent materials with these properties in the separation and analysis of algal toxins, focusing on carbon-based materials, metal organic frameworks (MOFs), covalent organic frameworks (COFs), molecularly imprinted polymers (MIPs), and their functionalized counterparts. Carbon-based materials, MOFs, and COFs have advantages such as large surface areas and abundant adsorption sites. These extraction materials are widely used in the separation and analysis of target substances in complex environmental, biological, and food samples owing to their excellent performance and unique microstructure. They are also the main adsorbents used for the extraction of algal toxins. These extraction materials play an essential role in the extraction of algal toxins, but they also present a number of limitations: (1) Carbon-based materials, MOFs, and COFs have relatively poor selective-adsorption ability towards target substances; (2) Most MOFs are unstable in aqueous solutions and challenging to apply during extraction from water-based sample solutions; (3) COFs mainly consist of lightweight elements, rendering them difficult to completely separate from sample solutions using centrifugal force, which limits their application range; (4) Although MIPs have good selectivity, issues such as template-molecule loss, slow mass-transfer rates, and low adsorption capacity must be addressed. Therefore, the design and preparation of novel functionalized extraction materials specifically tailored for algal toxins and studies on new composite extraction materials are highly desirable. This article collects representative literature from domestic and international research on algal-toxin analysis over the past decade, summarizes the relevant findings, categorizes the applications of novel functional materials in algal-toxin-extraction processes, and provides an outlook on their future development prospects.

CD39hi identifies an exhausted tumor-reactive CD8+ T cell population associated with tumor progression in human gastric cancer.

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.

Source analysis and health risk assessment of polycyclic aromatic hydrocarbon (PAHs) in total suspended particulate matter (TSP) from Bengbu, China.

The polycyclic aromatic hydrocarbon (PAH) concentrations in total suspended particulate matter (TSP) samples collected from October, 2021 to September, 2022 were analyzed to clarify the pollution characteristics and sources of 16 PAHs in the atmospheric TSP in Bengbu City. The ρ(PAHs) concentrations ranged from 1.71 to 43.85 ng/m3 and higher concentrations were detected in winter, followed by spring, autumn, and summer. The positive matrix factorization analysis revealed that, in spring and summer, PAH pollution was caused mainly by industrial emissions, gasoline and diesel fuel combustion, whereas in autumn and winter, it was coal, biomass and natural gas combustion. The cluster and potential source factor analyses showed that long-range transport was a significant factor. During spring, autumn, and winter, the northern and northwestern regions had a significant impact, whereas the coastal area south of Bengbu had the greatest influence in summer. The health risk assessment revealed that the annual total carcinogenic equivalent concentration values for PAHs varied from 0.0159 to 7.437 ng/m3, which was classified as moderate. Furthermore, the annual incremental lifetime cancer risk values ranged from 1.431 × 10-4 to 3.671 × 10-3 for adults and from 6.823 × 10-5 to 1.749 × 10-3 for children, which were higher than the standard.

Left endoscopic combined intrarenal surgery with electrocoagulation hemostasis and right flexible ureteroscopic lithotripsy for bilateral upper urinary tract stones: a case report.

Background: Percutaneous nephrolithotomy (PCNL) is the first-line treatment for large renal stones. However, multi-tract or staged procedures may be necessitated in bilateral or anatomically-complex stones to achieve stone clearance. Endoscopic combined intrarenal surgery (ECIRS) integrates the advantages of PCNL and retrograde intrarenal surgery. In this article, we detail a hybrid surgical technique adopted for the management of complex simultaneous bilateral upper urinary tract stones. In addition, we discuss the advantages and disadvantages of combining a variety of new techniques that may improve post-operative outcomes and patient satisfaction. Case Description: We report the case of a 36-year-old male with a large left renal pelvis stone, right proximal ureteric stone, and bilateral renal stones. Biochemical results showed raised inflammatory markers but he denied pre-stenting and staged surgery. After receiving 3-day antibiotic prophylaxis, he underwent an elective hybrid procedure. Under split-leg prone position, we performed a hybrid procedure that included left ECIRS with tubeless single-tract mini PCNL and left flexible ureteroscopy, and right flexible ureteroscopic lithotripsy. Hemostasis was achieved by electrocauterization with a novel device. The patient made an uneventful recovery. Follow-up computed tomography (CT) at 1-month revealed complete stone clearance. Conclusions: Unilateral ECIRS with tubeless single-tract mini PCNL with electrocoagulation hemostasis and adjacent retrograde intrarenal surgery in split-leg prone position is a safe, feasible, and efficient technique to manage large renal stones.

Morphological and Phylogenetic Characterization of Three Novel Thaxterogaster (Cortinariaceae) Species from China with an Emphasis on Their Subtropical Distribution.

Three new phlegmaciod species of Thaxterogaster, T. borealicremeolinus, T. rufopurpureus, and T. sinopurpurascens spp. nov., from subtropical China were described based on their morphological characteristics and molecular data. Thaxterogaster borealicremeolinus belongs to the sect. Cremeolinae and differs from the other species in this section in its larger basidiospores and its habitat in the Northern Hemisphere associated with Quercus sp. trees. Thaxterogaster rufopurpureus and T. sinopurpurascens belong to sect. Purpurascentes, in which T. rufopurpureus is characterized by a pileus with a reddish-brown coloration when mature and a clavate stipe, while T. sinopurpurascens is characterized by a violet basidiomata, except for a greyish orange to brown pileus, the distinctly marginate bulb of its stipe, and its distribution in subtropical China. The phylogenetic analyses were performed based on nrITS, and detailed descriptions of the new species are provided herein.

Surgical strategy and outcome in patients with bilateral proliferative diabetic retinopathy.

OBJECTIVES: To investigate the current surgery strategies for bilateral proliferative diabetic retinopathy (PDR), as well as the surgical outcomes of patients with bilateral PDR who underwent pars plana vitrectomy (PPV). MATERIALS: Patients undergoing bilateral vitrectomy for PDR from January 2019 to December 2020 at The Eye Hospital of Wenzhou Medical University were enrolled. Clinical data were collected from the electronic medical records. Factors associated with the time interval between the surgeries on two eyes and postoperative visual outcomes were analyzed. RESULTS: In total, 152 patients with bilateral PDR who underwent bilateral PPV were included in this analysis. Mean age was 53.7 ± 11.4 years. Compared with second-surgery eyes, 60.5% of first-surgery eyes had worse preoperative best-corrected visual acuity (BCVA). The overall PPV time (median, quartile range) between first and second surgeries eye was 1.40 (0.70, 3.15) months. Multivariate analysis showed that the preoperative BCVA of the second-surgery eye had a significant effect on the inter-surgery time interval (P = 0.048). First-surgery eyes had greater vision improvement than second-surgery eyes (Difference of the logarithm of the minimum angle of resolution [LogMAR] BCVA: - 1.00 [- 1.48, - 0.12] versus 0.00 [- 1.30, 0.00], respectively, P < 0.001), especially when eyes with poorer BCVA underwent PPV first (- 1.15 [- 1.87, - 0.54] versus 0.00 [- 0.70, 0.00], respectively, P < 0.001). CONCLUSIONS: Visual acuity is a significant factor that influences surgical strategies, including both surgery order and interval, for patients with bilateral PDR. The eyes operated upon first show more vision improvement due to prompt surgery.

Paper-based visualization of auramine O in food and drug samples with carbon dots-incorporated fluorescent microspheres as sensing element.

A paper-based assay for visualization of auramine O (AO) was for the first time established by using CFMs as a ratiometric fluorescent probe (RFP). The CFMs were melamine formaldehyde microspheres (MFMs) incorporated with carbon dots (CDs), where the CDs species as sensing units and MFMs as a signal amplification carrier. The proposed RFP can quantitatively measure AO content from 0.0 to 10.0 µM and exhibited an ultralow limit of detection (LOD, 15.7 nM). In particular, obvious luminescence color change of CFMs from blue to green was perceived with naked-eyes and therefore, a solution-based and a paper-based visualization platform were respectively proposed for on-site visual detection of AO with LODs of 1.15 µM and 0.83 µM, separately. Finally, those fluorescence methods were adopted in sensitively quantitative measurement of AO within various food and drug samples, providing new prospects for analysts and technical support in food quality monitoring.

Flexible ureterolithotripsy for the management of multiple gas-containing renal calculi: A case report and literature review.

Gas-containing renal stones (GCS) are rare urological entities. Current literature has suggested possible associations with premenopausal women, urinary tract infection, and metabolic diseases. We report the case of a 25-year-old young woman with no underlying co-morbidities who had multiple right GCS and suspected emphysematous pyelitis. Antibiotic therapy was initiated to control her urinary tract infection with E. coli. She then underwent elective right flexible ureteroscopy to relieve her ureteropelvic junction obstruction. Complete stone retrieval was achieved and she made an uneventful recovery with no stone recurrence during 1-year follow-up.

Acquisition, loss, and replication of functional modules promote the genetic diversity of Salmonella bacteriophages.

Owing to the threats that Salmonella poses to public health and the abuse of antimicrobials, bacteriophage therapy against Salmonella is experiencing a resurgence. Although several phages have been reported as safe and efficient for controlling Salmonella, the genetic diversity and relatedness among Salmonella phages remain poorly understood. In this study, whole-genome sequences of 91 Salmonella bacteriophages were obtained from the National Center for Biological Information genome database. Phylogenetic analysis, mosaic structure comparisons, gene content analysis, and orthologue group clustering were performed. Phylogenetic analysis revealed four singletons and two major lineages (I-II), including five subdividing clades, of which Salmonella phages belonging to morphologically distinct families were clustered in the same clade. Chimeric structures (n = 31), holin genes (n = 18), lysin genes (n = 66), DNA packaging genes (n = 55), and DNA metabolism genes (n = 24) were present in these phages. Moreover, phages from different subdivided clusters harboured distinct genes associated with host cell lysis, DNA packaging, and DNA metabolism. Notably, phages belonging to morphologically distinct families shared common orthologue groups. Although several functional modules of phages SS1 and SE16 shared > 99% nucleotide sequence identity with phages SI2 and SI23, the major differences between these phages were the absence and replication of functional modules. The data obtained herein revealed the genetic diversity of Salmonella phages at genomic, structural, and gene content levels. The genetic diversity of Salmonella phages is likely owing to the acquisition, loss, and replication of functional modules.

Potassium cobalt hexacyanoferrate as a peroxidase mimic for electrochemical immunosensing of Lactobacillus rhamnosus GG.

In this paper, the potassium cobalt hexacyanoferrate (II), K2CoFe(CN)6, with peroxidase-like activity was used for the fabrication of a novel label-free Lactobacillus rhamnosus GG (LGG) electrochemical immunosensor. The K2CoFe(CN)6 nanocubes were made by a simple hydrothermal method and followed by low-temperature calcination. In addition to structural characterization, the peroxidase-mimicking catalytic property of the material was confirmed by a chromogenic reaction. It is known that H2O2 can oxidize electroactive thionine molecules under the catalysis of horseradish peroxidase (HRP). In this nanozyme-based electrochemical immunoassay, due to the steric hindrance, the formation of immune-complex of LGG and LGG antibody on the modified GCE inhibits the catalytic activity of the peroxidase mimics of K2CoFe(CN)6 and thus reduced the current signal. Therefore, the developed electrochemical immunosensor achieved quantitative detection of LGG. Under optimal conditions, the linear range of the sensor was obtained from 101 to 106 CFU mL-1 with a minimum detection limit (LOD) of 12 CFU mL-1. Furthermore, the immunosensor was successfully applied in the quantitative detection of LGG in dairy product samples with recoveries ranging from 93.2% to 106.8%. This protocol presents a novel immunoassay method, which provides an alternative implementation pathway for the quantitative detection of microorganisms.

Biotransformation of gallate esters by a pH-stable tannase of mangrove-derived yeast Debaryomyces hansenii.

Introduction: Tannase is a crucial enzyme that finds wide applications in the pharmaceutical industry, feed processing, and beverage manufacturing. Although extensive studies have been conducted on tannases from fungi and bacteria, reports on tannases exhibiting favorable pH stability are relatively limited. Methods: In this study, a tannin-degrading strain Debaryomyces hansenii was screened to induce tannase production, and the corresponding tannase coding gene TANF was successfully cloned and expressed in Yarrowia lipolytica. SDS-PAGE analysis revealed that the purified TanF tannase had a molecular weight of approximately 70 kDa. Results and Discussion: The enzyme demonstrated optimal activity at 40°C and retained over 80% of its activity in the range of 35°C-60°C. Of particular interest, TanF exhibited remarkable enzyme activity at pH 5.0 and retained more than 70% of its relative activity across a wide pH range of 3.0-8.0. Furthermore, TanF exhibited broad substrate specificity for gallate esters. The final gallic acid production by TanF from tannic acid achieved 18.32 g/L. Therefore, the excellent properties TanF has been demonstrated to be an efficient tool for the preparation of gallic acid.

Surface engineering of magnetic peroxidase mimic using bacteriophage for high-sensitivity/specificity colorimetric determination of Staphylococcus aureus in food.

Herein, we proposed surface engineering of magnetic peroxidase mimic using bacteriophage by electrostatic interaction to prepare bacteriophage SapYZU15 modified Fe3O4 (SapYZU15@Fe3O4) for colorimetric determination of S. aureus in food. SapYZU15@Fe3O4 exhibits peroxidase-like activity, catalyzing 3,3',5,5'-tetramethylbenzidine (TMB) chromogenic reaction. After introducing S. aureus, peroxidase-like activity of SapYZU15@Fe3O4 was specifically inhibited, resulting in deceleration of TMB chromogenic reaction. This phenomenon benefits from the presence of unique tail protein gene in the bacteriophage SapYZU15 genome, leading to a specific biological interaction between S. aureus and SapYZU15. On basis of this principle, SapYZU15@Fe3O4 can be employed for colorimetric determination of S. aureus with a limiting detection (LOD), calculated as low as 1.2 × 102 CFU mL-1. With this proposed method, colorimetric detection of S. aureus in food was successfully achieved. This portends that surface engineering of nanozymes using bacteriophage has great potential in the field of colorimetric detection of pathogenic bacterium in food.

Incidental Finding of Intrarenal Foreign Guidewire During Percutaneous Nephrolithotomy: A Case Report and Literature Review.

BACKGROUND Percutaneous nephrolithotomy (PCNL) is indicated for large renal calculi (≥2 cm) and is often the treatment of choice due to its high success rate. Guidewire fragmentation is a rare procedural accident that can occur in PCNL but may be missed. Retention of the fragment within the upper urinary tract can lead to further complications, such as recurrent nephrolithiasis or impairment of renal function. CASE REPORT We present the case of a 54-year-old man who experienced right flank pain for 5 days. His history was significant for recurrent nephrolithiasis, managed by PCNL in other hospitals. The most recent procedure was conducted 4 years ago, and his perioperative course was uneventful. Preoperative computed tomography revealed right renal calculi and a C-shaped foreign body. He was scheduled for an elective PCNL. The foreign body was intraoperatively identified as a guidewire fragment and removed. CONCLUSIONS Currently, there is no standard management for intrarenal foreign bodies. Suspicion should be raised in young patients with recurrent stones within a short period of time. A thorough history on past urological interventions should be obtained. Symptoms can also have an insidious onset that could mimic nephrolithiasis or urinary tract infections. Extraction can be done via a standard minimally invasive approach. It is also the surgeon's responsibility to check the integrity of intraoperative instruments so as to minimize risks of complication and reassure the patient.

Lactic acid bacteria biofilms and their antimicrobial potential against pathogenic microorganisms.

The continuous growth of pathogenic microorganisms and associated biofilms poses severe public health challenges, particularly in food and clinical environments. However, these difficulties have enabled scientists to develop novel and safe methods for combating pathogens. The use of biofilms produced by lactic acid bacteria (LAB) against pathogenic bacteria has recently gained popularity. This review provides an in-depth look at LAB biofilms, their distribution, and mechanisms of action against pathogenic bacteria. More importantly, the bioactive substances produced by LAB-forming biofilm may be active against undesirable microorganisms and their products, which is of great interest in improving human health. Therefore, this review implies that a combination of LAB biofilms and other LAB products like bacteriocins could provide viable alternatives to traditional methods of combating pathogenic microorganisms and their biofilms.

Cerebral organoids transplantation repairs infarcted cortex and restores impaired function after stroke.

Stroke usually causes prolonged or lifelong disability, owing to the permanent loss of infarcted tissue. Although a variety of stem cell transplantation has been explored to improve neuronal defect behavior by enhancing neuroplasticity, it remains unknown whether the infarcted tissue can be reconstructed. We here cultured human cerebral organoids derived from human pluripotent stem cells (hPSCs) and transplanted them into the junction of the infarct core and the peri-infarct zone of NOD-SCID mice subjected to stroke. Months later, we found that the grafted organoids survived well in the infarcted core, differentiated into target neurons, repaired infarcted tissue, sent axons to distant brain targets, and integrated into the host neural circuit and thereby eliminated sensorimotor defect behaviors of stroke mice, whereas transplantation of dissociated single cells from organoids failed to repair the infarcted tissue. Our study offers a new strategy for reconstructing infarcted tissue via organoids transplantation thereby reversing stroke-induced disability.

Versatile dodecyl trimethyl ammonium bromide modified γ-FeOOH for simultaneous removal and determination of As(⠤).

Inorganic arsenic pollution in water spreads all over the world, tremendously threatening environmental safety and human health. Herein, versatile dodecyl trimethyl ammonium bromide modified γ-FeOOH (DTAB-γ-FeOOH) was prepared for sportive removal and visual determination of As(Ⅴ) in water. DTAB-γ-FeOOH displays a nanosheet-like structure with a high specific surface area calculated as 166.88 m2 g-1. Additionally, DTAB-γ-FeOOH shows peroxidase-mimicking feature, which can catalyze colorless TMB to generate blue oxidized TMB (TMBox) in presence of H2O2. Removal experiments show that DTAB-γ-FeOOH exhibits good As(Ⅴ) removal efficiency because modification of DTAB makes γ-FeOOH carry abundant positive charges, improving affinity between DTAB-γ-FeOOH and As(Ⅴ). It is found that theoretical maximum adsorption capacity is up to 126.91 mg g-1. Moreover, DTAB-γ-FeOOH can resist interference of most of co-existing ions. After that, As(Ⅴ) was detected based on peroxidase-like DTAB-γ-FeOOH. As(Ⅴ) can be adsorbed onto DTAB-γ-FeOOH surface, markedly inhibiting its peroxidase-like activity. Based on it, As(Ⅴ) ranging from 1.67 to 3333.33 µg L-1 can be well detected, with a low LOD (0.84 µg L-1). The successful sorptive removal and visual determination of As(Ⅴ) from real environmental water indicated that DTAB-γ-FeOOH has great potential in the treatment of As(Ⅴ)-containing environment water.

Isolation and characterization of the new isolated bacteriophage YZU-L1 against Citrobacter freundii from a package-swelling of meat product.

Citrobacter freundii is an important foodborne pathogen that can cause urethritis, bacteremia, necrotizing abscess, and meningitis in infants. In this study, a gas-producing isolate from vacuum-packed meat products was identified as C. freundii by 16S rDNA. In addition, a new virulent phage YZU-L1, which could specifically lyse C. freundii, was isolated from sewage samples in Yangzhou. Transmission electron microscopy showed that phage YZU-L1 had a polyhedral head of 73.51 nm in diameter and a long tail of 161.15 nm in length. According to phylogenetic analysis employing the terminase large subunit, phage YZU-L1 belonged to the Demerecviridae family and the Markadamsvirinae subfamily. The burst size was 96 PFU/cell after 30 min of latent period and 90 min of rising period. Phage YZU-L1 could maintain high activity at pH of 4-13, and resist 50 °C for up to 60 min. The complete genome of YZU-L1 was 115,014 bp double-stranded DNA with 39.94% G + C content, encoding 164 open reading frames (ORFs), without genes encoding for virulence, antibiotic resistance, or lysogenicity. Phage YZU-L1 treatment significantly reduced the viable bacterial count of C. freundii in a sterile fish juice model, which is expected to be a natural agent for the biocontrol of C. freundii in foods.

WGS analysis of two Staphylococcus aureus bacteriophages from sewage in China provides insights into the genetic feature of highly efficient lytic phages.

The study of bacteriophages is experiencing a resurgence with the increasing development of antimicrobial resistance in Staphylococcus aureus. Nonetheless, the genetic features of highly efficient lytic S. aureus phage remain to be explored. In this study, two lytic S. aureus phages, SapYZU11 and SapYZU15, were isolated from sewage samples from Yangzhou, China. The phage morphology, one-step growth, host spectrum and lytic activity of these phages were examined, and their whole-genome sequences were analysed and compared with 280 published genomes of staphylococcal phages. The structural organisation and genetic contents of SapYZU11 and SapYZU15 were investigated. The Podoviridae phage SapYZU11 and Herelleviridae phage SapYZU15 effectively lysed all of the 53 S. aureus strains isolated from various sources. However, SapYZU15 exhibited a shorter latent period, larger burst size and stronger bactericidal ability with an anti-bacterial rate of approximately 99.9999% for 24 h. Phylogenetic analysis revealed that Herelleviridae phages formed the most ancestral clades and the S. aureus Podoviridae phages were clustered in the staphylococcal Siphoviridae phage clade. Moreover, phages in different morphology families contain distinct types of genes associated with host cell lysis, DNA packaging and lysogeny. Notably, SapYZU15 harboured 13 DNA metabolism-related genes, 5 lysin genes, 1 holin gene and 1 DNA packaging gene. The data suggest that S. aureus Podoviridae and Siphoviridae phages originated from staphylococcal Herelleviridae phages, and the module exchange of S. aureus phages occurred in the same morphology family. Moreover, the extraordinary lytic capacity of SapYZU15 was likely due to the presence of specific genes associated with DNA replication, DNA packaging and the lytic cycle.

Ketone bodies promote stroke recovery via GAT-1-dependent cortical network remodeling.

Stroke is a leading cause of adult disability worldwide, and better drugs are needed to promote functional recovery after stroke. Growing evidence suggests the critical role of network excitability during the repair phase for stroke recovery. Here, we show that ß-hydroxybutyrate (ß-HB), an essential ketone body (KB) component, is positively correlated with improved outcomes in patients with stroke and promotes functional recovery in rodents with stroke during the repair phase. These beneficial effects of ß-HB depend on HDAC2/HDAC3-GABA transporter 1 (GAT-1) signaling-mediated enhancement of excitability and phasic GABA inhibition in the peri-infarct cortex and structural and functional plasticity in the ipsilateral cortex, the contralateral cortex, and the corticospinal tract. Together with available clinical approaches to elevate KB levels, our results offer a clinically translatable means to promote stroke recovery. Furthermore, GAT-1 can serve as a pharmacological target for developing drugs to promote functional recovery after stroke.