High salt condition alters LPS synthesis and induces the emergence of drug resistance mutations in Helicobacter pylori.

The burgeoning emergence of drug-resistant Helicobacter pylori strains poses a significant challenge to the clinical success of eradication therapies and is primarily attributed to mutations within drug-targeting genes that lead to antibiotic resistance. This study investigated the effect of high salt conditions on the occurrence of drug-resistance mutations in H. pylori. We found that high salt condition significantly amplifies the frequency of drug resistance mutations in H. pylori. This can be chiefly attributed to our discovery indicating that high salt concentration results in elevated reactive oxygen species (ROS) levels, initiating DNA damage within H. pylori. Mechanistically, high salt condition suppresses lipopolysaccharide (LPS) synthesis gene expression, inducing alterations in the LPS structure and escalating outer membrane permeability. This disruption of LPS synthesis attenuates the expression and activity of SodB, facilitates increased ROS levels, and consequently increases the drug resistance mutation frequency. Impairing LPS synthesis engenders a reduction in intracellular iron levels, leading to diminished holo-Fur activity and increased apo-Fur activity, which represses the expression of SodB directly. Our findings suggest a correlation between high salt intake and the emergence of drug resistance in the human pathogen H. pylori, implying that dietary choices affect the risk of emergence of antimicrobial resistance.IMPORTANCEDrug resistance mutations mainly contribute to the emergence of clinical antibiotic-resistant Helicobacter pylori, a bacterium linked to stomach ulcers and cancer. In this study, we explored how elevated salt conditions influence the emergence of drug resistance in H. pylori. We demonstrate that H. pylori exhibits an increased antibiotic resistance mutation frequency when exposed to a high salt environment. We observed an increase in reactive oxygen species (ROS) under high salt conditions, which can cause DNA damage and potentially lead to mutations. Moreover, our results showed that high salt condition alters the bacterium's lipopolysaccharide (LPS) synthesis, leading to a reduced expression of SodB in a Fur-dependent manner. This reduction, in turn, elevates ROS levels, culminating in a higher frequency of drug-resistance mutations. Our research underscores the critical need to consider environmental influences, such as diet and lifestyle, in managing bacterial infections and combating the growing challenge of antibiotic resistance.

Versatile Design of NO-Generating Proteolipid Nanovesicles for Alleviating Vascular Injury.

Vascular injury is central to the pathogenesis and progression of cardiovascular diseases, however, fostering alternative strategies to alleviate vascular injury remains a persisting challenge. Given the central role of cell-derived nitric oxide (NO) in modulating the endogenous repair of vascular injury, NO-generating proteolipid nanovesicles (PLV-NO) are designed that recapitulate the cell-mimicking functions for vascular repair and replacement. Specifically, the proteolipid nanovesicles (PLV) are versatilely fabricated using membrane proteins derived from different types of cells, followed by the incorporation of NO-generating nanozymes capable of catalyzing endogenous donors to produce NO. Taking two vascular injury models, two types of PLV-NO are tailored to meet the individual requirements of targeted diseases using platelet membrane proteins and endothelial membrane proteins, respectively. The platelet-based PLV-NO (pPLV-NO) demonstrates its efficacy in targeted repair of a vascular endothelium injury model through systemic delivery. On the other hand, the endothelial cell (EC)-based PLV-NO (ePLV-NO) exhibits suppression of thrombosis when modified onto a locally transplanted small-diameter vascular graft (SDVG). The versatile design of PLV-NO may enable a promising therapeutic option for various vascular injury-evoked cardiovascular diseases.

Coherent detection of the rotational Doppler effect measurement based on triple Fourier transform.

In recent years, the rotational Doppler effect (RDE) has been widely used in rotational motion measurement. However, the performance of existing detection systems based on the RDE are generally limited by the drastic reduction of signal-to-noise ratio (SNR) due to the influence of atmospheric turbulence, partial obscuration of the vortex beam (VB) during propagation, and misalignment between the optical axis of VB and the rotational axis of the object, which poses a challenge for practical applications. In this paper, we proposed a coherent detection method of the RDE measurement based on triple Fourier transform. First, the weak RDE signal in backscattered light is amplified by using the balanced homodyne detection method, and the amplified signal still retains the same characteristic of severe broadening in the frequency domain as the original signal. Furthermore, we proposed the triple Fourier transform to extract the broadened RDE frequency shift signal after the coherent amplification. The proposed method significantly improves the SNR of RDE measurement and facilitates the accurate extraction of rotational speed, which helps to further improve the RDE detection range and promote its practical application.

Identification of eight genes associated with recurrent patellar dislocation.

The inheritance of recurrent patellar dislocation (RPD) is known, but the susceptible gene remains unidentified. Here, we performed the first whole exome sequencing (WES) cohort study to identify the susceptible genes. The results showed eight genes were associated with this disease. Notably, the carboxypeptidase D (CPD) gene showed the highest relevance based on its gene function and tissue expression. Single-cell sequencing results indicate that the CPD gene is involved in the pathophysiological process of RPD through granulocytes. Implicated pathways include nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and Wnt/ß-catenin signaling, potentially influencing CPD's role in RPD pathogenesis. This study identified the susceptible gene and investigates the potential pathogenesis of RPD, which provided a new prospect for the understanding of RPD. Besides, it would offer the theoretical basis for disease prevention and genetic counseling.

Quantitative analysis of the impact of respiratory state on the heartbeat-induced movements of the heart and its substructures.

PURPOSE: This study seeks to examine the influence of the heartbeat on the position, volume, and shape of the heart and its substructures during various breathing states. The findings of this study will serve as a valuable reference for dose-volume evaluation of the heart and its substructures in radiotherapy for treating thoracic tumors. METHODS: Twenty-three healthy volunteers were enrolled in this study, and cine four-dimensional magnetic resonance images were acquired during periods of end-inspiration breath holding (EIBH), end-expiration breath holding (EEBH), and deep end-inspiration breath holding (DIBH). The MR images were used to delineate the heart and its substructures, including the heart, pericardium, left ventricle (LV), left ventricular myocardium, right ventricle (RV), right ventricular myocardium (RVM), ventricular septum (VS), atrial septum (AS), proximal and middle portions of the left anterior descending branch (pmLAD), and proximal portion of the left circumflex coronary branch (pLCX). The changes in each structure with heartbeat were compared among different respiratory states. RESULTS: Compared with EIBH, EEBH increased the volume of the heart and its substructures by 0.25-3.66%, while the average Dice similarity coefficient (DSC) increased by - 0.25 to 8.7%; however, the differences were not statistically significant. Conversely, the VS decreased by 0.89 mm in the left-right (LR) direction, and the displacement of the RV in the anterior-posterior (AP) direction significantly decreased by 0.76 mm (p < 0.05). Compared with EIBH and EEBH, the average volume of the heart and its substructures decreased by 3.08-17.57% and 4.09-20.43%, respectively, during DIBH. Accordingly, statistically significant differences (p < 0.05) were observed in the volume of the heart, pericardium, LV, RV, RVM, and AS. The average DSC increased by 0-37.04% and - 2.6 to 32.14%, respectively, with statistically significant differences (p < 0.05) found in the right ventricular myocardium and interatrial septum. Furthermore, the displacements under DIBH decreased in the three directions (i.e.,- 1.73 to 3.47 mm and - 0.36 to 2.51 mm). In this regard, the AP displacement of the heart, LV, RV, RVM, LR direction, LV, RV, and AS showed statistically significant differences (p < 0.05). The Hausdorff distance (HD) of the heart and its substructures under the three breathing states are all greater than 11 mm. CONCLUSION: The variations in the displacement and shape alterations of the heart and its substructures during cardiac motion under various respiratory states are significant. When assessing the dose-volume index of the heart and its substructures during radiotherapy for thoracic tumors, it is essential to account for the combined impacts of cardiac motion and respiration.

Role of conventional MD staging in modern era of hydrops MR imaging.

Objective/Hypothesis: This study correlated stage of Meniere's disease (MD) with MR imaging of endolymphatic hydrops (EH) to assess the role of MD staging in modern era. Study Design: Retrospective study. Methods: Fifty-four MD patients (60 ears) underwent an inner ear test battery and were further confirmed by MR imaging. Sixty MD ears were divided into stages I-IV, and hydrops MR images at each stage were compared. Results: Hydrops MRI demonstrated that EH at the cochlea with respective Grades 0/I/II were 3/7/1 ears for stage I, 0/5/3 ears for stage II, 1/6/26 ears for stage III and 0/2/6 ears for stage IV. Significant relationship was not identified between MD stage and grades of cochlear hydrops. Similarly, no significant relationship was shown between MD stage and grades of vestibular (saccular/utricular) hydrops. The optimal cutoff value of four-tone average for predicting severe type (Grade II-III) cochlear/vestibular EH was 48 dB, which was within the stage III. Hence, prevalence of severe type (Grade II) cochlear EH in stages III (79%) and IV (75%) was significantly higher than stages I (9%) and II (38%). Similarly, severe type saccular/utricular EH in stages III (64%) and IV (75%) also showed significantly higher than stages I (18%) and II (25%). Conclusion: Although conventional MD staging fails to correlate with the grades of EH on hydrops MRI, late-stage MD may indicate heightened EH severity in the cochlea and vestibule. Level of Evidence: 4.

Prognostic iron-metabolism signature robustly stratifies single-cell characteristics of hepatocellular carcinoma.

Cancer immunotherapy has shown to be a promising method in treating hepatocellular carcinoma (HCC), but suboptimal responses in patients are attributed to cellular and molecular heterogeneity. Iron metabolism-related genes (IRGs) are important in maintaining immune system homeostasis and have the potential to help develop new strategies for HCC treatment. Herein, we constructed and validated the iron-metabolism gene prognostic index (IPX) using univariate Cox proportional hazards regression and LASSO Cox regression analysis, successfully categorizing HCC patients into two groups with distinct survival risks. Then, we performed single-sample gene set enrichment analysis, weighted correlation network analysis, gene ontology enrichment analysis, cellular lineage analysis, and SCENIC analysis to reveal the key determinants underlying the ability of this model based on bulk and single-cell transcriptomic data. We identified several driver transcription factors specifically activated in specific malignant cell sub-populations to contribute to the adverse survival outcomes in the IPX-high subgroup. Within the tumor microenvironment (TME), T cells displayed significant diversity in their cellular characteristics and experienced changes in their developmental paths within distinct clusters identified by IPX. Interestingly, the proportion of Treg cells was increased in the high-risk group compared with the low-risk group. These results suggest that iron-metabolism could be involved in reshaping the TME, thereby disrupting the cell cycle of immune cells. This study utilized IRGs to construct a novel and reliable model, which can be used to assess the prognosis of patients with HCC and further clarify the molecular mechanisms of IRGs in HCC at single-cell resolution.

Flow velocity and light intensity combination is important for Microcystis aeruginosa physical suppression.

The cyanobacterial response to flow velocity or light intensity deviates from the combined effect of both factors. The responses of Microcystis aeruginosa to different combinations of flow velocities and light intensities were tested. Growth (OD730 and protein), stress (catalase, ascorbate peroxidase, and glutathione peroxidase), and photosynthetic ability (chlorophyll-a and fluorescence) parameters of M. aeruginosa were measured to evaluate the effects of different combinations. Exposure to different flow velocity-light combinations significantly affected the growth and physiology of M. aeruginosa. Flow velocities of 0.4 m s-1 showed a prominent influence on most of the measured parameters compared with no flow velocity or higher flow velocity conditions. The 1.2-m s-1 flow velocity and high light intensity (1200 µmol m-2  s-1 ) exposure caused a significant elevation in oxidative stress. Lower velocities are beneficial for M. aeruginosa at light stress, whereas extreme velocities are adverse and elevate the stress. Two categories of light-velocity combinations were identified as preferred and extreme categories, depending on whether they suppressed or supported M. aeruginosa growth. In controlling cyanobacteria blooms using flow or high-intensity light, it is imperative to consider the interaction of these two factors, as their combined effects can significantly vary the stress levels in cyanobacteria. A new system, designed to minimize mechanical damage on M. aeruginosa, was used to generate flow velocities. Additionally, the combined effects of flow velocities and light intensities have been considered for the first time. PRACTITIONER POINTS: Flow velocity can influence the effect of light on Microcystis aeruginosa. High light exposure effect on Microcystis aeruginosa can be reduced by low flow velocity. High flow velocity and high light exposure increase the stress on Microcystis aeruginosa. Different light intensities and flow velocity combinations changed Microcystis aeruginosa stress physiology.

Recoverability of Microcystis aeruginosa and Pseudanabaena foetida Exposed to a Year-Long Dark Treatment.

Cyanobacteria are a significant primary producer and pioneer species that play a vital role in ecological reconstruction, especially in aquatic environments. Cyanobacteria have excellent recovery capacity from significant stress exposure and are thus suggested as bioreserves, even for space colonization programs. Few studies have been conducted on the recovery capacity after experiencing stress. Long-duration darkness or insufficient light is stressful for photosynthetic species, including cyanobacteria, and can cause chlorosis. Cyanobacterial recovery after extensive exposure to darkness has not yet been studied. In this experiment, Microcystis aeruginosa and Pseudanabaena foetida were subjected to a year-long darkness treatment, and the change in recovery capacity was measured in monthly samples. Cyanobacterial growth, chlorophyll-a concentration, oxidative stress, and photosynthetic capacity were evaluated. It was found that the rapid recovery capacity of the two species remained even after one year of darkness treatment. However, the H2O2 content of recovered samples of both M. aeruginosa and P. foetida experienced significant changes at six-seven months, although the photosynthetic capacity of both cyanobacteria species was maintained within the healthy range. The chlorophyll-a and carotenoid content of the recovered samples also changed with increasing darkness. The results showed that long-term dark treatment had time-dependent effects but different effects on M. aeruginosa and P. foetida. However, both cyanobacteria species can recover rapidly after one year of dark treatment.

Anemia is associated with long-term exposure to PM2.5 and its components: a large population-based study in Southwest China.

Background: Anemia is linked to PM2.5 (particulate matter with aerodynamic diameters of ⩽2.5 µm) exposure, which can increase the risk of various negative health outcomes. It remains unclear which PM2.5 components are associated with anemia and the respective contribution of each component to this association. Objective: This study aimed at investigating the association between PM2.5 and anemia in the general population and to identify the most critical PM2.5 toxic components in this association. Design: Cross-sectional study. Methods: Our study involved a large cohort of 73,511 individuals aged 30-79 from China's multi-ethnic population. We employed satellite observations and the chemical transport model (GEOS-Chem)to estimate the long-term exposure to PM2.5 and its components. Anemia was defined, according to WHO guidelines, as Hb levels below 130 g/L for men and below 120 g/L for women. Through logistic regression, we investigated the association between PM2.5 components and anemia. By utilizing weighted quantile sum (WQS) analysis, we identified key components and gained insights into their combined impact on anemia. Overall, our study sheds light on the relationship between PM2.5 exposure, its constituents, and the risk of anemia in a large cohort. Results: PM2.5 and three components, nitrate (NIT), organic matter (OM), and soil particles (SOIL), were associated with anemia. Per-standard deviation increase in the 3-year average concentrations of PM2.5 [odds ratio (OR): 1.14, 95% confidence interval (CI): 1.01, 1.28], NIT (1.20, 1.06, 1.35), OM (1.17, 1.04, 1.32), and SOIL (1.22, 1.11, 1.33) were associated with higher odds of anemia. In WQS regression analysis, the WQS index was associated with anemia (OR: 1.29, 95% CI: 1.13, 1.47). SOIL has the highest weight among all PM2.5 components. Conclusions: Long-term exposure to PM2.5 and its constituents is associated with anemia. Moreover, SOIL might be the most critical component of the relationship between PM2.5 and anemia. Our research increases the evidence of the association between PM2.5 and anemia in the general population, and targeted emission control measures should be taken into consideration to mitigate the adverse effects of PM2.5-related anemia.

Ambient PM2.5 Components Are Associated With Bone Strength: Evidence From a China Multi-Ethnic Study.

CONTEXT: The relationship between the components of particulate matter with an aerodynamic diameter of 2.5 or less (PM2.5) and bone strength remains unclear. OBJECTIVE: Based on a large-scale epidemiologic survey, we investigated the individual and combined associations of PM2.5 and its components with bone strength. METHODS: A total of 65 906 individuals aged 30 to 79 years were derived from the China Multi-Ethnic Cohort Annual average concentrations of PM2.5 and its components were estimated using satellite remote sensing and chemical transport models. Bone strength was expressed by the calcaneus quantitative ultrasound index (QUI) measured by quantitative ultrasound. The logistic regression model and weighted quantile sum method were used to estimate the associations of single and joint exposure to PM2.5 and its components with QUI, respectively. RESULTS: Our analysis shows that per-SD increase (µg/m3) in 3-year average concentrations of PM2.5 (mean difference [MD] -7.38; 95% CI, -8.35 to -6.41), black carbon (-7.91; -8.90 to -6.92), ammonium (-8.35; -9.37 to -7.34), nitrate (-8.73; -9.80 to -7.66), organic matter (-4.70; -5.77 to -3.64), and soil particles (-5.12; -6.10 to -4.15) were negatively associated with QUI. In addition, these associations were more pronounced in men, and people older than 65 years with a history of smoking and chronic alcohol consumption. CONCLUSION: We found that long-term exposure to PM2.5 and its components may lead to reduced bone strength, suggesting that PM2.5 and its components may potentially increase the risk of osteoporosis and even fracture. Nitrate may be responsible for increasing its risk to a greater extent.

A de novo heterozygous variant in ACOX1 gene cause Mitchell syndrome: the first case in China and literature review.

BACKGROUND: Mitchell syndrome (MITCH) is a rare autosomal dominant hereditary disorder, characterized by episodic demyelination, sensorimotor polyneuropathy and hearing loss. MITCH is caused by heterozygous mutation in the ACOX1 gene, which encodes straight-chain acyl-CoA oxidase, on chromosome 17q25.1.  Only 5 unrelated patients have been reported so far, and no reports from China. Here, we describe the first MITCH case in a Chinese individual. CASE PRESENTATION: A 7-year-old girl initially presented with diffuse desquamatory rash at age 3. Her clinical symptoms in order of presentation were diffuse desquamatory rash, gait instability, ptosis with photophobia, hearing loss, abdominal pain, diarrhea, nausea, and dysuria. Genetic analysis demonstrated that the patient carried a heterozygous variant c.710A>G(p.Asp237Ser) in the ACOX1 gene, which can cause MITCH symptoms. This is the first MITCH case with gastrointestinal and urinary tract symptoms. After administrating N acetylcysteine amide (NACA), some symptoms were relieved and the patient's condition improved. CONCLUSION: This is the first MITCH case in the Chinese population, and we expanded the genotype spectrum of it. The p.Asp237Ser may be a mutational hotspot in ACOX1 regardless of race. In terms of diagnosis, patients with recurrent rash, gait instability, and hearing loss with some autonomic symptoms should raise the suspicion of MITCH and proper and prompt treatment should be given.

Sediment mercury concentration of a subtropical mangrove wetland responded to Hong Kong-Shenzhen industrial development since the 1960s.

Mercury (Hg) in coastal wetlands is of great concern due to its acute toxicity. We measured the total Hg content (THg) from a 210Pb-dated sediment core obtained from the Futian mangrove wetland in Shenzhen Bay, South China to explore the historical variation and possible sources. Our results extend the sediment THg record back to 1960 and reveal three distinct intervals. Interval I (1960-1974) has low and increasing THg values, averaging 83.0 µg/kg; Interval II (1975-1984) witnesses a remarkably increase, peaking in 1980 (261.6 µg/kg) then remaining elevated; Interval III (1985-2014) shows a steady reduction, averaging 118.4 µg/kg. The good correlation among THg, TOC, and Hg/TOC, and the downstream decrease in monitoring sediment THg consistently suggest that the bulk THg are mainly sourced from the Shenzhen River discharge. The different timing in industrial development attributes the elevated THg concentrations during 1975-1984 to Hong Kong industrial sewage pollution.

Androgen Receptor Transcriptionally Inhibits Programmed Death Ligand-1 Expression and Influences Immune Escape in Bladder Cancer.

In multiple clinical trials, immune checkpoint blockade-based immunotherapy has shown significant therapeutic efficacy in bladder cancer (BCa). Sex is closely related to the incidence rate and prognosis of BCa. As one of the sex hormone receptors, the androgen receptor (AR) is a well-known key regulator that promotes the progression of BCa. However, the regulatory mechanism of AR in the immune response of BCa is still unclear. In this study, the expression of AR and programmed death ligand 1 (PD-L1) was negatively correlated in BCa cells, clinical tissues, and tumor data extracted from The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort. A human BCa cell line was transfected to alter the expression of AR. The results show that AR negatively regulated PD-L1 expression by directly binding to AR response elements on the PD-L1 promoter region. In addition, AR overexpression in BCa cells significantly enhanced the antitumor activity of cocultured CD8+ T cells. Injection of anti-PD-L1 monoclonal antibodies into C3H/HeN mice significantly suppressed tumor growth, and stable expression of AR dramatically enhanced the antitumor activity in vivo. In conclusion, this study describes a novel role of AR in regulating the immune response to BCa by targeting PD-L1, thus providing potential therapeutic strategies for immunotherapy in BCa.

Functionalization of in vivo tissue-engineered living biotubes enhance patency and endothelization without the requirement of systemic anticoagulant administration.

Vascular regeneration and patency maintenance, without anticoagulant administration, represent key developmental trends to enhance small-diameter vascular grafts (SDVG) performance. In vivo engineered autologous biotubes have emerged as SDVG candidates with pro-regenerative properties. However, mechanical failure coupled with thrombus formation hinder translational prospects of biotubes as SDVGs. Previously fabricated poly(ε-caprolactone) skeleton-reinforced biotubes (PBs) circumvented mechanical issues and achieved vascular regeneration, but orally administered anticoagulants were required. Here, highly efficient and biocompatible functional modifications were introduced to living cells on PB lumens. The 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-methoxy (DMPE)-PEG-conjugated anti-coagulant bivalirudin (DPB) and DMPE-PEG-conjugated endothelial progenitor cell (EPC)-binding TPS-peptide (DPT) modifications possessed functionality conducive to promoting vascular graft patency. Co-modification of DPB and DPT swiftly attained luminal saturation without influencing cell viability. DPB repellent of non-specific proteins, DPB inhibition of thrombus formation, and DPB protection against functional masking of DPT's EPC-capture by blood components, which promoted patency and rapid endothelialization in rat and canine artery implantation models without anticoagulant administration. This strategy offers a safe, facile, and fast technical approach to convey additional functionalization to living cells within tissue-engineered constructs.

Construction of Rapid Extracellular Matrix-Deposited Small-Diameter Vascular Grafts Induced by Hypoxia in a Bioreactor.

Cardiovascular disease has become one of the most globally prevalent diseases, and autologous or vascular graft transplantation has been the main treatment for the end stage of the disease. However, there are no commercialized small-diameter vascular graft (SDVG) products available. The design of SDVGs is promising in the future, and SDVG preparation using an in vitro bioreactor is a favorable method, but it faces the problem of long-term culture of >8 weeks. Herein, we used different oxygen (O2) concentrations and mechanical stimulation to induce greater secretion of extracellular matrix (ECM) from cells in vitro to rapidly prepare SDVGs. Culturing with 2% O2 significantly increased the production of the ECM components and growth factors of human dermal fibroblasts (hDFs). To accelerate the formation of ECM, hDFs were seeded on a polycaprolactone (PCL) scaffold and cultured in a flow culture bioreactor with 2% O2 for only 3 weeks. After orthotopic transplantation in rat abdominal aorta, the cultured SDVGs (PCL-decellularized ECM) showed excellent endothelialization and smooth muscle regeneration. The vascular grafts cultured with hypoxia and mechanical stimulation could accelerate the reconstruction speed and obtain an improved therapeutic effect and thereby provide a new research direction for improving the production and supply of SDVGs.

Renal Endothelial Cell-Targeted Extracellular Vesicles Protect the Kidney from Ischemic Injury.

Endothelial cell injury plays a critical part in ischemic acute kidney injury (AKI) and participates in the progression of AKI. Targeting renal endothelial cell therapy may ameliorate vascular injury and further improve the prognosis of ischemic AKI. Here, P-selectin as a biomarker of ischemic AKI in endothelial cells is identified and P-selectin binding peptide (PBP)-engineered extracellular vesicles (PBP-EVs) with imaging and therapeutic functions are developed. The results show that PBP-EVs exhibit a selective targeting tendency to injured kidneys, while providing spatiotemporal information for the early diagnosis of AKI by quantifying the expression of P-selectin in the kidneys by molecular imaging. Meanwhile, PBP-EVs reveal superior nephroprotective functions in the promotion of renal repair and inhibition of fibrosis by alleviating inflammatory infiltration, improving reparative angiogenesis, and ameliorating maladaptive repair of the renal parenchyma. In conclusion, PBP-EVs, as an ischemic AKI theranostic system that is designed in this study, provide a spatiotemporal diagnosis in the early stages of AKI to help guide personalized therapy and exhibit superior nephroprotective effects, offering proof-of-concept data to design EV-based theranostic strategies to promote renal recovery and further improve long-term outcomes following AKI.

Vertigo/dizziness following COVID-19 vaccination.

PURPOSE: This study assessed the vertigo/dizziness in patients following COVID-19 vaccination. PATIENTS AND METHODS: From July 2021 to June 2022, totaling 50 patients with dizzy spells following COVID-19 vaccination by AZ (AstraZeneca-Oxford University, AZD1222), BNT (Pfizer-BioNTech, BNT162b2) or Moderna (Moderna, mRNA-1273) vaccine were enrolled in this study. The interval from vaccination to the onset of vertigo/dizziness was compared with inter-episodic interval of vertigo/dizziness in the same patients, but without vaccination, during past one year (2020). RESULTS: The incidences of severe systemic complication per 106 shots were 0.86 for Moderna vaccine, 1.22 for AZ vaccine, and 1.23 for BNT vaccine. Conversely, rate of post-vaccination vertigo/dizziness was noted in the Moderna group (66 %), followed by the AZ group (20 %) and the BNT (14 %) group, meaning that type of COVID-19 vaccine may affect various organ systems. The median time to the onset of vertigo/dizziness following vaccination is 10d, which is consistent with the onset of IgG production, and significantly less than inter-episodic interval (84d) in the same patients without vaccination. CONCLUSION: Post-vaccination vertigo/dizziness can manifest as exacerbation of previous neurotological disorder. The median time to the onset of vertigo/dizziness following COVID-19 vaccination is 10d. Since the outcome is fair after supportive treatment, the immunomodulatory effect of the vaccines does not undermine the necessity of the COVID-19 vaccination.

Cobalt loaded electrospun poly(ε-caprolactone) grafts promote antibacterial activity and vascular regeneration in a diabetic rat model.

Diabetes has been associated with postoperative complications, such as increased risk of tissue infection and impaired tissue repair caused by destabilization of hypoxia-inducible factor-1α (HIF-1α). Consequently, it is imperative to fabricate anti-bacterial and pro-regenerative small-diameter vascular grafts for treating cardiovascular disease in diabetic patients. Herein, we developed electrospun cobalt ion (Co2+)-loaded poly (ε-caprolactone) (PCL) microfiber vascular grafts (PCL-Co grafts). The released Co2+ significantly increased the stabilization of HIF-1α in high-glucose (HG)-treated HUVECs (HG-HUVECs) and macrophages (HG-macrophages). This resulted in enhanced cell migration, nitric oxide production, and secretion of bioactive factors by HG-HUVECs, and polarization of HG-macrophages toward M2 phenotypes in vitro. The Co2+ also conferred anti-bacterial properties to the grafts, while not perturbing the inherent anti-bacterial activities of HG-macrophages. Following abdominal artery implantation into type 2 diabetes mellitus (T2DM) rats, PCL-Co grafts were evaluated for performance in infection (grafts pre-contaminated with Staphylococcus aureus) and prophylaxes models (grafts alone). PCL-Co grafts prevented the incidence of subsequent infection in prophylaxes model and effectively inhibited the bacterial growth in the infection model. PCL-Co grafts also significantly enhanced cellularization, vascularization, endothelialization, contractile SMC regeneration and macrophages polarization in both models. Collectively, PCL-Co grafts exhibited the potential to combat infection and improve tissue regeneration under diabetes conditions.

Virome Analysis of Normal and Growth Retardation Disease-Affected Macrobrachium rosenbergii.

The giant freshwater prawn, Macrobrachium rosenbergii, is an important aquaculture species in China. Growth retardation disease (GRD) is a common contagious disease in M. rosenbergii, resulting in slow growth and precocious puberty in prawns, and has caused growing economic losses in the M. rosenbergii industry. To investigate the viral diversity of M. rosenbergii and identify potentially high-risk viruses linked to GRD, virome analysis of the GRD-affected and normal M. rosenbergii was carried out using next-generation sequencing (NGS). A total of 327 contigs (>500 bp) were related to viral sequences belonging to 23 families/orders and a group of unclassified viruses. The majority of the viral contigs in M. rosenbergii belonged to the order Picornavirales, with the Solinviviridae family being the most abundant in both the diseased and normal groups. Furthermore, 16 RNA viral sequences with nearly complete genomes were characterized and phylogenetically analyzed, belonging to the families Solinviviridae, Flaviviridae, Polycipiviridae, Marnaviridae, and Dicistroviridae as well as three new clades of the order Picornavirales. Notably, the cross-species transmission of a picorna-like virus was observed between M. rosenbergii and plants. The "core virome" seemed to be present in the diseased and normal prawns. Still, a clear difference in viral abundance was observed between the two groups. These results showed that the broad diversity of viruses is present in M. rosenbergii and that the association between viruses and disease of M. rosenbergii needs to be further investigated. IMPORTANCE Growth retardation disease (GRD) has seriously affected the development and economic growth of the M. rosenbergii aquaculture industry. Our virome analysis showed that diverse viral sequences were present in M. rosenbergii, significantly expanding our knowledge of viral diversity in M. rosenbergii. Some differences in viral composition were noted between the diseased and normal prawns, indicating that some viruses become more abundant in occurrences or outbreaks of diseases. In the future, more research will be needed to determine which viruses pose a risk for M. rosenbergii. Our study provides important baseline information contributing to disease surveillance and risk assessment in M. rosenbergii aquaculture.