Weissella cibaria Relieves Gut Inflammation Caused by Escherichia coli through Inflammation Modulation and Gut Microbiota Regulation.

The emergence of multi-drug-resistant (MDR) pathogens has considerably challenged the development of new drugs. Probiotics that inhibit MDR pathogens offer advantages over chemical antibiotics and drugs due to their increased safety and fewer side effects. This study reported that Weissella cibaria P-8 isolated from pickles showed excellent antibacterial activity against intestinal pathogens, particularly the antibacterial activity against MDR Escherichia coli B2 was the highest. This study showed that the survival rates of W. cibaria P-8 at pH 2.0 and 0.3% bile salt concentration were 72% and 71.56%, respectively, and it still had antibacterial activity under pepsin, trypsin, protease K, and catalase hydrolysis. Moreover, W. cibaria P-8 inhibits the expression of inflammatory factors interleukin-1ß, tumor necrosis factor-α, and interleukin-6, upregulates the interleukin-10 level, and increases total antioxidant capacity and superoxide dismutase enzyme activity in serum. W. cibaria P-8 also efficiently repairs intestinal damage caused by E. coli infection. The gut microbiota analysis demonstrated that W. cibaria P-8 colonizes the intestine and increases the abundance of some beneficial intestinal microorganisms, particularly Prevotella. In conclusion, W. cibaria P-8 alleviated MDR E. coli-induced intestinal inflammation by regulating inflammatory cytokine and enzyme activity and rebalancing the gut microbiota, which could provide the foundation for subsequent clinical analyses and probiotic product development.

Neofunctionalization of an OMT cluster dominates polymethoxyflavone biosynthesis associated with the domestication of citrus.

Polymethoxyflavones (PMFs) are a class of abundant specialized metabolites with remarkable anticancer properties in citrus. Multiple methoxy groups in PMFs are derived from methylation modification catalyzed by a series of hydroxylases and O-methyltransferases (OMTs). However, the specific OMTs that catalyze the systematic O-methylation of hydroxyflavones remain largely unknown. Here, we report that PMFs are highly accumulated in wild mandarins and mandarin-derived accessions, while undetectable in early-diverging citrus species and related species. Our results demonstrated that three homologous genes, CreOMT3, CreOMT4, and CreOMT5, are crucial for PMF biosynthesis in citrus, and their encoded methyltransferases exhibit multisite O-methylation activities for hydroxyflavones, producing seven PMFs in vitro and in vivo. Comparative genomic and syntenic analyses indicated that the tandem CreOMT3, CreOMT4, and CreOMT5 may be duplicated from CreOMT6 and contributes to the genetic basis of PMF biosynthesis in the mandarin group through neofunctionalization. We also demonstrated that N17 in CreOMT4 is an essential amino acid residue for C3-, C5-, C6-, and C3'-O-methylation activity and provided a rationale for the functional deficiency of OMT6 to produce PMFs in early-diverging citrus and some domesticated citrus species. A 1,041-bp deletion in the CreOMT4 promoter, which is found in most modern cultivated mandarins, has reduced the PMF content relative to that in wild and early-admixture mandarins. This study provides a framework for reconstructing PMF biosynthetic pathways, which may facilitate the breeding of citrus fruits with enhanced health benefits.

Convection-Enhanced Drug Delivery: Experimental and Analytical Studies of Infusion Behavior in an In Vitro Brain Surrogate.

Convection-enhanced drug delivery (CED) directly infuses drugs with a large molecular weight toward target cells as a therapeutic strategy for neurodegenerative diseases and brain cancers. Despite the success of many previous in vitro experiments on CED, challenges still remain. In particular, a theoretical predictive model is needed to form a basis for treatment planning, and developing such a model requires well-controlled injection tests that can rigorously capture the convective (advective) and diffusive transport of an infusate. For this purpose, we investigated the advection-diffusion transport of an infusate (bromophenol blue solution) in the brain surrogate (0.2% w/w agarose gel) at different injection rates, ranging from 0.25 to 4 µL/min, by closely monitoring changes in the color intensity, propagation distance, and injection pressures. One dimensional closed-form solution was examined with two variable sets, such as the mathematically calculated coefficient of molecular diffusion and average velocity, and the hydraulic dispersion coefficient and seepage velocity by the least squared method. As a result, the seepage velocity was greater than the average velocity to some extent, particularly for the later infusion times. The poroelastic deformation in the brain surrogate might lead to changes in porosity, and consequently, slight increases in the actual flow velocity as infusion continues. The limitation of efficiency of the single catheter was analyzed by dimensionless analysis. Lastly, this study suggests a simple but robust approach that can properly capture the convective (advective) and diffusive transport of an infusate in an in vitro brain surrogate via well-controlled injection tests.

What Is Medical Extended Reality? A Taxonomy Defining the Current Breadth and Depth of an Evolving Field.

Medical extended reality (MXR) has emerged as a dynamic field at the intersection of health care and immersive technology, encompassing virtual, augmented, and mixed reality applications across a wide range of medical disciplines. Despite its rapid growth and recognition by regulatory bodies, the field lacks a standardized taxonomy to categorize its diverse research and applications. This American Medical Extended Reality Association guideline, authored by the editorial board of the Journal of Medical Extended Reality, introduces a comprehensive taxonomy for MXR, developed through a multidisciplinary and international collaboration of experts. The guideline seeks to standardize terminology, categorize existing work, and provide a structured framework for future research and development in MXR. An international and multidisciplinary panel of experts was convened, selected based on publication track record, contributions to MXR, and other objective measures. Through an iterative process, the panel identified primary and secondary topics in MXR. These topics were refined over several rounds of review, leading to the final taxonomy. The taxonomy comprises 13 primary topics that jointly expand into 180 secondary topics, demonstrating the field's breadth and depth. At the core of the taxonomy are five overarching domains: (1) technological integration and innovation; (2) design, development, and deployment; (3) clinical and therapeutic applications; (4) education, training, and communication; and (5) ethical, regulatory, and socioeconomic considerations. The developed taxonomy offers a framework for categorizing the diverse research and applications within MXR. It may serve as a foundational tool for researchers, clinicians, funders, academic publishers, and regulators, facilitating clearer communication and categorization in this rapidly evolving field. As MXR continues to grow, this taxonomy will be instrumental in guiding its development and ensuring a cohesive understanding of its multifaceted nature.

CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation.

Cholesterol metabolism has important roles in maintaining membrane integrity and countering the development of diseases such as obesity and cancers. Cancer cells sustain cholesterol biogenesis for their proliferation and microenvironment reprograming even when sterols are abundant. However, efficacy of targeting cholesterol metabolism for cancer treatment is always compromised. Here it is shown that CSN6 is elevated in HCC and is a positive regulator of hydroxymethylglutaryl-CoA synthase 1 (HMGCS1) of mevalonate (MVA) pathway to promote tumorigenesis. Mechanistically, CSN6 antagonizes speckle-type POZ protein (SPOP) ubiquitin ligase to stabilize HMGCS1, which in turn activates YAP1 to promote tumor growth. In orthotopic liver cancer models, targeting CSN6 and HMGCS1 hinders tumor growth in both normal and high fat diet. Significantly, HMGCS1 depletion improves YAP inhibitor efficacy in patient derived xenograft models. The results identify a CSN6-HMGCS1-YAP1 axis mediating tumor outgrowth in HCC and propose a therapeutic strategy of targeting non-alcoholic fatty liver diseases- associated HCC.

High stability of EEG spectral power across polysomnography and multiple sleep latency tests in good sleepers and chronic insomniacs.

To assess the stability of electroencephalographic (EEG) spectral features across overnight polysomnography (PSG) and daytime multiple sleep latency tests (MSLTs) in chronic insomniacs (CIs) and normal controls (NCs). A total of 20 NCs and 22 CIs underwent standard PSG and MSLTs. Spectral analyses were performed on EEG data from PSG and MSLTs and absolute and relative power in central, frontal and occipital channels were obtained for wake (W) and non-rapid eye movement sleep stage 1 and 2 (N1, N2). Intraclass correlation coefficients (ICCs) were used to assess the stability of EEG spectral power across PSG and MSLTs for W, N1 and N2. The absolute power of all frequency bands except delta exhibited high stability across PSG and MSLTs in both NCs and CIs (ICCs ranged from 0.430 to 0.978). Although delta absolute power was stable in NCs during N1 and N2 stages (ICCs ranged from 0.571 to 0.835), it tended to be less stable in CIs during W and sleep stages (ICCs ranged from 0.042 to 0.807). We also observed lower stability of relative power compared to absolute power though the majority of relative power outcomes maintained high stability in both groups (ICCs in relative power ranged from 0.044 to 0.962). Most EEG spectral bandwidths across PSG and MSLT in W, N1 and N2 show high stability in good sleepers and chronic insomniacs. EEG signals from either an overnight PSG or a daytime MSLT may be useful for reliably exploring EEG spectral features during wakefulness or sleep.

Rapid and sensitive detection of two fungal pathogens in soybeans using the recombinase polymerase amplification/CRISPR-Cas12a method for potential on-site disease diagnosis.

BACKGROUND: Diaporthe aspalathi and Diaporthe caulivora are two of the fungal pathogens causing soybean stem canker (SSC) in soybean, which is one of the most widespread diseases in soybean growing regions and can cause 100% loss of yield. Current methods for the detection of fungal pathogens, including morphological identification and molecular detection, are mostly limited by the need for professional laboratories and staff. To develop a detection method for potential on-site diagnosis for two of the fungal pathogens causing SSC, we designed a rapid assay combining recombinase polymerase amplification (RPA) and CRISPR-Cas12a-based diagnostics to specifically detect D. aspalathi and D. caulivora. RESULTS: The translation elongation factor 1-alpha gene was employed as the target gene to evaluate the specificity and sensitivity of this assay. The RPA/CRISPR-Cas12a system has excellent specificity to distinguish D. aspalathi and D. caulivora from closely related species. The sensitivities of RPA/CRISPR-Cas12a-based fluorescence detection and lateral flow assay for D. aspalathi and D. caulivora are 14.5 copies and 24.6 copies, respectively. This assay can detect hyphae in inoculated soybean stems at 12 days after inoculation and has a recovery as high as 86% for hyphae-spiked soybean seed powder. The total time from DNA extraction to detection was not more than 60 min. CONCLUSION: The method developed for rapid detection of plant pathogens includes DNA extraction with magnetic beads or rapid DNA extraction, isothermal nucleic acid amplification at 39 °C, CRISPR-Cas12a cleavage reaction at 37 °C, and lateral flow assay or endpoint fluorescence visualization at room temperature. The RPA and CRISPR-Cas12a reagents can be preloaded in the microcentrifuge tube to simplify the procedures in the field. Both RPA and CRISPR-Cas12a reaction can be realized on a portable incubator, and the results are visualized using lateral flow strips or portable flashlight. This method requires minimal equipment and operator training, and has promising applications for rapid on-site disease screening, port inspection, or controlling fungal pathogen transmission in crop. © 2023 Society of Chemical Industry.

The percentage of circulating fibrocytes is associated with increased morbidity of pulmonary hypertension in patients on hemodialysis.

INTRODUCTION: Pulmonary hypertension (PH) is highly prevalent in patients receiving dialysis. The precise mechanisms underlying PH in hemodialysis (HD) patients have not been adequately addressed. Emerging experimental evidence indicates that circulating fibrocytes may contribute significantly to this process. METHODS: We measured the proportion of circulating fibrocytes using flow cytometry analysis and prospectively analyzed patients during HD from February 1, 2017, to February 1, 2022. Then we investigated correlations between circulating fibrocytes, inflammation cytokines, PH, and their affective factors that predict the prognosis of HD patients. RESULTS: The cohort included 192 patients. During a follow-up of 5 years, we registered 66 all-cause deaths, and 11 patients received kidney transplantation. The incidence of PH among HD patients was 30.9%. We found that the circulating fibrocyte level significantly correlated with pulmonary arterial systolic pressure (r = 0.412, p < 0.05). In the multiple logistic regression analysis, the percentage of circulating fibrocytes was an independent predictor of PH (odds ratio [OR]: 2.080, 95% confidence interval [CI]: 1.539-2.812, p < 0.001). Controlling for confounding covariates in the multivariate Cox regression models, the presence of PH conferred an increased risk of all-cause mortality in HD patients [hazard ratio (HR): 2.183, 95% CI:1.257-3.788, p = 0.006]. CONCLUSION: The prevalence of PH was high in HD patients and was associated with higher all-cause mortality. Higher circulating fibrocyte level was an independent predictor of the presence of PH; these fibrocytes may serve as early detection markers and novel therapeutic targets.

Polysomnographic findings of myotonic dystrophy type 1/type 2: evidence from case-control studies.

STUDY OBJECTIVES: This study explores polysomnographic and multiple sleep latency test (MSLT) differences between myotonic dystrophy type 1/type 2 (DM1/DM2) patients and controls. METHODS: An electronic literature search was conducted in MEDLINE, EMBASE, All EBM databases, and Web of Science from inception to Aug 2023. RESULTS: Meta-analyses revealed significant reductions in sleep efficiency, N2 percentage, mean SpO2, and MSLT measured mean sleep latency, and increases in N3 sleep, wake time after sleep onset, apnea hypopnea index, and periodic limb movement index in DM1 patients compared with controls. However, any differences of polysomnographic sleep change between DM2 patients and controls could not be established due to limited available studies. CONCLUSIONS: Multiple significant polysomnographic abnormalities are present in DM1. More case-control studies evaluating polysomnographic changes in DM2 compared with controls are needed.

Endogenous Zinc-Ion-Triggered In Situ Gelation Enables Zn Capture to Reprogram Benign Hyperplastic Prostate Microenvironment and Shrink Prostate.

Benign prostatic hyperplasia (BPH) as the leading cause of urination disorder is still a refractory disease, and there have no satisfied drugs or treatment protocols yet. With identifying excessive Zn2+ , inflammation, and oxidative stress as the etiology of aberrant hyperplasia, an injectable sodium alginate (SA) and glycyrrhizic acid (GA)-interconnected hydrogels (SAGA) featuring Zn2+ -triggered in situ gelation are developed to load lonidamine for reprogramming prostate microenvironment and treating BPH. Herein, SAGA hydrogels can crosslink with Zn2+ in BPH via coordination chelation and switch free Zn2+ to bound ones, consequently alleviating Zn2+ -arisen inflammation and glycolysis. Beyond capturing Zn2+ , GA with intrinsic immunoregulatory property can also alleviate local inflammation and scavenge reactive oxygen species (ROS). Intriguingly, Zn2+ chelation-bridged interconnection in SAGA enhances its mechanical property and regulates the degradation rate to enable continuous lonidamine release, favoring hyperplastic acini apoptosis and further inhibiting glycolysis. These multiple actions cooperatively reprogram BPH microenvironment to alleviate characteristic symptoms of BPH and shrink prostate. RNA sequencing reveals that chemotaxis, glycolysis, and tumor necrosis factor (TNF) inflammation-related pathways associated with M1-like phenotype polarization are discerned as the action rationales of such endogenous Zn2+ -triggered in situ hydrogels, providing a candidate avenue to treat BPH.

Optimizing the ordering of the Hadamard masks of ghost imaging suitable for the efficient face reconstruction using the max-projection method.

One crucial component of ghost imaging (GI) is the encoded mask. Higher-quality reconstruction at lower sampling rates is still a major challenge for GI. Inspired by deep learning, max-projection method is proposed in the paper to reorder the Hadamard masks for its efficient and rapid reconstruction. The simulations demonstrated that max-projection ordering with only 20 face training images yielded excellent reconstruction outcomes. In noise-free simulations, at an ultralow sampling rate of 5%, the PSNR of the max-projection ordering was 1.1 dB higher than that of the cake-cutting ordering with the best performance in the reference group. In noisy simulations, at ultralow sampling rates, the retrieved images remained almost identical to their noise-free counterparts. Irrespective of the presence or absence of noise, the max-projection ordering guaranteed the highest fidelity of image reconstruction at ultralow sampling rates. The reconstruction time was reduced to mere milliseconds, thereby enabling swift visualization of dynamic phenomena. Accordingly, the max-projection ordering Hadamard matrix offers a promising solution for real-time GI due to its higher reconstruction quality, stronger noise immunity and millisecond reconstruction time.

An improved ligand-assisted reprecipitation method to synthesize aqueous-phase CsPbBr3 perovskite nanocrystals and investigate their electrochemiluminescence behavior.

We propose a novel ligand-assisted reprecipitation method to synthesize aqueous-phase CsPbBr3 nanocrystals, the fluorescence intensity of which remained at 51% after 120 h. As a multifunctional additive, cesium trifluoroacetate (Cs-TFA) can improve the surface adsorption energy and induce nanocrystals to show significant anodic electrochemiluminescence (ECL) and stable cathodic ECL performances.

A Review on the Coalescence of Confined Drops with a Focus on Scaling Laws for the Growth of the Liquid Bridge.

The surface-tension-driven coalescence of drops has been extensively studied because of the omnipresence of the phenomenon and its significance in various natural and engineering systems. When two drops come into contact, a liquid bridge is formed between them and then grows in its lateral dimensions. As a result, the two drops merge to become a bigger drop. The growth dynamics of the bridge are governed by a balance between the driving force and the viscous and inertial resistances of involved liquids, and it is usually represented by power-law scaling relations on the temporal evolution of the bridge dimension. Such scaling laws have been well-characterized for the coalescence of unconfined or freely suspended drops. However, drops are often confined by solid or liquid surfaces and thus are a different shape from spheres, which affects their coalescence dynamics. As such, the coalescence of confined drops poses more complicated interfacial fluid dynamics challenges compared to that of unconfined drops. Although there have been several studies on the coalescence of confined drops, they have not been systematically reviewed in terms of the properties and geometry of the confining surface. Thus, we aim to review the current literature on the coalescence of confined drops in three categories: drop coalescence on a solid surface, drop coalescence on a deformable surface, and drop coalescence between two parallel surfaces with a small gap (i.e., Hele-Shaw cell), with a focus on power-law scaling relations, and to suggest challenges and outlooks for future research on the phenomena.

Mechanism of Weiwei granules in the treatment of chronic active Helicobacter pylori gastritis with atrophy based on the TLR4/NF-κB/COX-2 inflammatory signaling pathway.

OBJECTIVE: Our paper aimed to elucidate the mechanism of Weiwei granules in the treatment of Helicobacter pylori (Hp)-positive chronic atrophic gastritis (CAG) based on the TLR4/NF-κB/COX-2 inflammatory signaling pathway. METHODS: Hp-positive CAG patients were randomized into the control group (treated with quadruple therapy) or the observation group (treated with Weiwei granules based on the control group). The clinical efficacy, Hp clearance rate, and efficacy of traditional Chinese medicine (TCM) symptoms were compared between the two groups after six months of treatment. The scores of various histopathology variables, serum levels of inflammatory factors (interleukin-6 [IL-6], interleukin-8 [IL-8], and tumor necrosis factor-alpha [TNF-α]), gastrin-17 (G-17) and motilin (MTL), pepsinogen (PG) I and PG II, as well as serum levels of gastrointestinal hormone endothelin (ET), epidermal growth factor (EGF), and calcitonin gene-related peptide (CGRP), were compared between the two groups before and after treatment. TLR4, NF-κB, and COX-2 mRNA levels were compared in gastric mucosal tissues before and after treatment in the two groups. RESULTS: After treatment, the clinical efficacy, Hp clearance rate, and efficacy of TCM symptoms of patients in the observation group were higher than those in the control group. After treatment, the scores of various histopathology variables, serum levels of inflammatory factors (IL-6, IL-8, and TNF-α), gastrointestinal hormones (ET and EGF), and the expression levels of TLR4, NF-κB, and COX-2 mRNA in the gastric mucosal tissues were lower and G-17, MTL, CGRP, and PG I levels were higher in the observation group than in the control group. CONCLUSION: Weiwei granules can effectively improve Hp-positive CAG patients and reduce the expression levels of TLR4, NF-κB, and COX-2.

An improved algorithm for thermal compensation of synchrotron radiation optical mirrors based on Hessian matrix.

The heaters-based thermal-compensated adaptive adjustment of a reflection mirror at Shanghai high repetition rate X-ray Free-Electron Laser and extreme light facility (SHINE) is presented here based on finite element analysis. The correction performance of different control algorithms [singular value decomposition and gradient descent (GD)] is analyzed and compared. This study has demonstrated that a significant control algorithm can further improve the surface shape accuracy of the mirror. After optimizing the mirror control algorithm, the calculated slope errors and height errors of the mirror are reduced to nearly less than 50 nrad rms and 0.5 nm rms, respectively. The optimization result indicates that the GD control algorithm based on the Hessian matrix exhibits superior performance and practicality compared to the control algorithm before optimization.

IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma.

IDH1 mutations frequently occur early in human glioma. While IDH1 mutation has been shown to promote gliomagenesis via DNA and histone methylation, little is known regarding its regulation in antiviral immunity. Here, we discover that IDH1 mutation inhibits virus-induced interferon (IFN) antiviral responses in glioma cells. Mechanistically, D2HG produced by mutant IDH1 enhances the binding of DNMT1 to IRF3/7 promoters such that IRF3/7 are downregulated, leading to impaired type I IFN response in glioma cells, which enhances the susceptibility of gliomas to viral infection. Furthermore, we identify DNMT1 as a potential biomarker predicting which IDH1mut gliomas are most likely to respond to oncolytic virus. Finally, both D2HG and ectopic mutant IDH1 can potentiate the replication and oncolytic efficacy of VSVΔ51 in female mouse models. These findings reveal a pivotal role for IDH1 mutation in regulating antiviral response and demonstrate that IDH1 mutation confers sensitivity to oncolytic virotherapy.

Seasonal variations in the diversity and benthic community structure of subtidal artificial oyster reefs adjacent to the Luanhe River Estuary, Bohai Sea.

Artificial oyster reefs provide important spawning and nursery grounds for a variety of fishes and large mobile crustaceans. Between July 2016 and May 2017, seasonal surveys of species composition and community structure were performed in the artificial oyster reef area and control area adjacent to the Luanhe River Estuary in China. During the survey year, 56 species belonging to 50 genera, 45 families, and 19 orders were recorded. The dominant economically important fish and mobile crustaceans were Hexagrammos otakii, Pholis fangi, Sebastes schlegelii, Charybdis japonica, and Oratosquilla oratoria. Resident fishes belonged to the Cynoglossidae, Paralichthyidae, Pleuronectidae, and Gobiidae families. Seasonally important fish species included Lateolabrax japonicus, Konosirus punctatus, Thryssa kammalensis, Hexagrammos agrammus, and Acanthopagrus schlegelii. The ranges of H' values among stations were 1.18-2.16, 0.65-1.75, 1.18-2.06, and 0.62-1.92 in spring, summer, autumn, and winter, respectively. The benthic organisms present in the community of artificial oyster reef areas can be classified into groups according to month and season. The abundance biomass curves showed that the oyster reef area in spring, autumn, and winter experienced low disturbance, whereas the community structure in summer was subject to large variations from external disturbance. We also found that as the age of the oyster reefs increased, the percentage of oysters in the low shell height group (< 40 mm) decreased. The oyster density was 324 ind/m2 for the reef created in 2016, 724 ind/m2 for the reef created in 2015, and 364 ind/m2 for the reef created in 2013. These findings can be used to develop suitable management strategies for the sustainable maintenance of artificial oyster reef ecosystems.

Targeting VCP potentiates immune checkpoint therapy for colorectal cancer.

Immune checkpoint blockade therapies are still ineffective for most patients with colorectal cancer (CRC). Immunogenic cell death (ICD) enables the release of key immunostimulatory signals to drive efficient anti-tumor immunity, which could be used to potentiate the effects of immune checkpoint inhibitors. Here, we showed that inhibition of valosin-containing protein (VCP) elicits ICD in CRC. Meanwhile, VCP inhibitor upregulates PD-L1 expression and compromises anti-tumor immunity in vivo. Mechanistically, VCP transcriptionally regulates PD-L1 expression in a JAK1-dependent manner. Combining VCP inhibitor with anti-PD1 remodels tumor immune microenvironment and reduces tumor growth in mouse models of CRC. Addition of oncolytic virus further augments the therapeutic activity of the combination regimen. Our study shows the molecular mechanism for regulating PD-L1 expression by VCP and suggests that inhibition of VCP has the potential to increase the efficacy of immunotherapy in CRC.