Small regulatory RNA RSaX28 promotes virulence by reinforcing the stability of RNAIII in community-associated ST398 clonotype Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a notorious pathogen that cause metastatic or complicated infections. Hypervirulent ST398 clonotype strains, remarkably increased in recent years, dominated Community-associated S. aureus (CA-SA) infections in the past decade in China. Small RNAs like RNAIII have been demonstrated to play important roles in regulating the virulence of S. aureus, however, the regulatory roles played by many of these sRNAs in the ST398 clonotype strains are still unclear. Through transcriptome screening and combined with knockout phenotype analysis, we have identified a highly transcribed sRNA, RSaX28, in the ST398 clonotype strains. Sequence analysis revealed that RSaX28 is highly conserved in the most epidemic clonotypes of S. aureus, but its high transcription level is particularly prominent in the ST398 clonotype strains. Characterization of RSaX28 through RACE and Northern blot revealed its length to be 533nt. RSaX28 is capable of promoting the hemolytic ability, reducing biofilm formation capacity, and enhancing virulence of S. aureus in the in vivo murine infection model. Through IntaRNA prediction and EMSA validation, we found that RSaX28 can specifically interact with RNAIII, promoting its stability and positively regulating the translation of downstream alpha-toxin while inhibiting the translation of Sbi, thereby regulating the virulence and biofilm formation capacity of the ST398 clonotype strains. RSaX28 is an important virulence regulatory factor in the ST398 clonotype S. aureus and represents a potential important target for future treatment and immune intervention against S. aureus infections.

Joint intra and inter-channel nonlinear compensation scheme based on improved learned digital back propagation for WDM systems.

In this paper, we improve the learned digital back propagation (LDBP) and propose a novel joint intra and inter-channel nonlinearity compensation scheme for polarization division multiplexing wavelength-division multiplexed (PDM-WDM) systems. From the perspective of interpretable neural network, the scheme realizes the alternating compensation of chromatic dispersion (CD) and nonlinearity based on physical models. The chromatic dispersion compensation (CDC) adopts one-dimensional convolution operation in the time domain. Moreover, the pulse-broadening effect is introduced into the overlap-and-save method. For nonlinear compensation, the improved joint model is applied, and the impact of the intra-channel pulse broadening and the walk-off effect between different channels caused by CD on the nonlinear effect is considered. To validate the effectiveness of the proposed scheme, we construct an 11-channel simulation system of 36 GBaud PDM uniform 16 quadrature amplitude modulation (PDM-16QAM) 1600 km and 64 GBaud PDM-64QAM 400 km, as well as a 5-channel experimental system of 28 GBaud PDM-16QAM 806.4 km. The simulation results show that the performance of PDM-16QAM with 0.5 steps per span and PDM-64QAM with 2 steps per span improve the Q-factor by approximately 0.75 dB and 0.54 dB at the optimal launch power, compared with the linear compensation scheme. The transmission performance of PDM-16QAM is higher than that of digital back propagation with 5 steps per span (DBP-5StPS), and the complexity is only 31.36% of that of DBP-5StPS. The performance of PDM-64QAM is higher than that of DBP-10StPS, with a complexity of 62.72%. The experimental results show that the performance of PDM-16QAM with 0.5 steps per span is improved with 0.86 dB Q-factor improvement compared with the linear compensation scheme at the optimal launch power, and the performance of the proposed scheme is higher than that of DBP-5StPS with a complexity of only 23.68%.

Outer membrane vesicles mediating horizontal transfer of the epidemic blaOXA-232 carbapenemase gene among Enterobacterales.

OXA-232 is one of the most common OXA-48-like carbapenemase derivatives and is widely disseminated in nosocomial settings across countries. The blaOXA-232 gene is located on a 6-kb non-conjugative ColKP3-type plasmid, while the dissemination of blaOXA-232 into different Enterobacterales species and the polyclonal dissemination of OXA-232-producing K. pneumoniae revealed the horizontal transfer of blaOXA-232. However, it's still unclear how this non-conjugative ColKP3 plasmid could facilitate the mobilization of blaOXA-232. Here, we observed the in vivo intraspecies transfer of blaOXA-232 during a nosocomial outbreak of OXA-232-producing K. pneumoniae. We demonstrated the presence of ColKP3 OXA-232 plasmid in the outer membrane vesicles (OMVs) derived from clinical isolates, and OMVs could facilitate the horizontal transfer of blaOXA-232 among Enterobacterales. In contrast, for the most prevalent carbapenemase genes, including blaKPC-2 and blaNDM-1, though the presence of carbapenemase genes and plasmid backbones in the vesicular lumen was observed, OMVs couldn't promote effective transformation, probably due to the low copy number of plasmids in clinical isolates and the low number of plasmids loaded into vesicles. Conjugation assay revealed that the epidemic IncX3 NDM-1 and IncFII(pHN7A8)/IncR KPC-2 plasmids were conjugative and could be horizontally transferred via independent conjugation or with the help of a co-existent conjugative plasmid. For the large-size and low-copy number conjugative plasmids carrying carbapenemase genes, OMVs-mediated gene exchange may only serve as an alternative pathway for horizontal transfer. In conclusion, diverse mobilization strategies were employed by plasmids harboring carbapenemase genes, and plasmids display a proper choice of mobility pathway due to their individual properties.

Effect of hip osteoarthritis on total hip replacement failure and revision: a focused study on athletic populations

Objective:This study aims to analyze the specific impact of hip osteoarthritis on the failure and subsequent revision of total hip replacements, with a particular focus on athletic populations. Considering the unique biomechanical demands and higher physical activity levels of athletes, the study seeks to understand how these factors influence post-surgical outcomes in cases of hip osteoarthritis.Methods:The research involved collecting and analyzing data from athletes who had undergone total hip replacement surgeries due to hip osteoarthritis. Patient demographics such as age, gender, and the severity of the disease were recorded. The study performed a detailed correlation analysis to evaluate the influence of hip osteoarthritis on the failure rates of total hip replacements in this specific group. It particularly focused on hip failure caused by arthritis, cement fixation failure in aseptic arthritis cases, and cemented hip failure due to primary inflammation.Results:The findings indicate that in athletic populations, hip osteoarthritis is significantly correlated with higher failure rates after total hip replacement, with an influence rate of 30.64%. This rate is notably higher compared to general population statistics, underscoring the unique challenges faced in treating athletes. The study also found a notable correlation between the type and severity of arthritis and the failure modes of hip replacements, including issues related to cement fixation.Conclusion:This study highlights the significant impact of hip osteoarthritis on the failure of total hip replacements in athletes, a group that typically places higher physical demands on hip joints post-surgery (AU)

Nanosecond pulsed electric field stimulates CD103+ DC accumulation in tumor microenvironment via NK-CD103+ DC crosstalk.

CD103+ DC is crucial for antitumor immune response. As a promising local therapy on cancers, nanosecond pulsed electric field (nsPEF) has been widely reported to stimulate anti-tumor immune response, but the underlying relationship between intratumoral CD103+ DC and nsPEF treatment remains enigmatic. Here, we focused on the behavior of CD103+ DC in response to nsPEF treatment and explored the underlying mechanism. We found that the nsPEF treatment led to the activation and accumulation of CD103+ DC in tumor. Depletion of CD103+ DC via Batf3-/- mice demonstrated CD103+ DC was necessary for intratumoral CD8+ T cell infiltration and activation in response to nsPEF treatment. Notably, NK cells recruited CD103+ DC into nsPEF-treated tumor through CCL5. Inflammatory array revealed CD103+ DC-derived IL-12 mediated the CCL5 secretion in NK cells. In addition, the boosted activation and infiltration of intratumoral CD103+ DC were abolished by cGAS-STING pathway inhibition, following IL-12 and CCL5 decreasing. Furthermore, nsPEF treatment promoting CD103+ DC-mediated antitumor response enhanced the effects of CD47 blockade strategy. Together, this study uncovers an unprecedented role for CD103+ DC in nsPEF treatment-elicited antitumor immune response and elucidates the underlying mechanisms.

CircRNA-SCAF8 promotes vascular endothelial cell pyroptosis by regulating the miR-93-5p/TXNIP axis. / 环状RNA-SCAF8通过miR-93-5p/TXNIPé€šè·¯ä¿ƒè¿›è¡€ç®¡å† çš®ç»†èƒžç„¦äº¡.

OBJECTIVES: To investigate the role and mechanism of circRNA-SR-related CTD associated factor 8 (SCAF8) in regulating endothelial cell pyroptosis in high glucose environment. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured and divided into six groups. The normal control group and high glucose control group were cultured in cell culture medium with 5 and 33 mmol/L glucose, respectively. The RNA control group, circRNA-SCAF8 inhibition group, miR-93-5p overexpression group and miR-93-5p inhibition group were added with non-functional siRNA, circRNA-SCAF8 inhibitor, miR-93-5p overexpression molecule and miR-93-5p inhibitor in high glucose environment, respectively. Cell viability and pyroptosis were detected by cell counting kit-8 (CCK-8) assay, flow cytometry and Hoechst 33342/propidium iodide fluorescence double staining. Western blotting and enzyme-linked immunosorbent assay were used to detect the expression of pyroptosis-related factors including apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartic acid specific protease-1 (caspase-1) and Gasdermin D (GSDMD), NOD like receptor protein 3 (NLRP-3), thioredoxin interacting proteins (TXNIP), IL-18 and IL-1ß. The expression of circRNA-SCAF8, miR-93-5p and TXNIP was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fluorescence in situ hybridization (FISH) was used to locate circRNA-SCAF8 and miR-93-5p. Dual luciferase assay was used to verify the targeted regulatory relationship between miR-93-5p and upstream and downstream molecules. RESULTS: Compared with the RNA control group, the cell survival rate of circRNA-SCAF8 inhibition group and miR-93-5p overexpression group increased (both P<0.01), the pyroptosis decreased (both P<0.01), and the expressions of pyroptosis-related factors such as TXNIP, NLRP-3, caspase-1, GSDMD, ASC, IL-18 and IL-1ß were significantly decreased (all P<0.05). The expression of miR-93-5p was significantly increased after inhibition of circRNA-SCAF8 (P<0.01), and the expression of circRNA-SCAF8 tended to decrease after overexpression of miR-93-5p, but with no statistical significance (P>0.05). Dual luciferase assay showed that miR-93-5p downre-gulated circRNA-SCAF8 expression by binding to the 3 ´ UTR region of circRNA-SCAF8, and miR-93-5p downregulated TXNIP expression by binding to the 3 ´ UTR region of TXNIP. FISH showed that circRNA-SCAF8 and miR-93-5p were both located in the cytoplasm and were highly associated in the cells. qRT-PCR showed that the relative expression of TXNIP increased or decreased after overexpression or inhibition of miR-93-5p compared with the RNA control group, respectively (both P<0.05), suggesting that miR-93-5p could regulate TXNIP gene expression. CONCLUSIONS: CircRNA-SCAF8/miR-93-5p/TXNIP axis is involved in the regulation of pyroptosis in HUVECs under high glucose.

A systematic review and meta-analysis of primary bypass surgery compared with bypass surgery after endovascular treatment in peripheral artery disease patients.

OBJECTIVE: Both bypass surgery and endovascular treatment are well-recognized interventions for the treatment of peripheral artery disease; however, the effect of failed endovascular treatment on subsequent surgeries remains controversial. A systematic review was conducted to compare the outcomes of primary bypass and bypass surgery after endovascular treatment. METHODS: Three academic databases (Embase, PubMed, and Scopus) were searched from their inception to August 2022. Two independent investigators searched for studies that reported the outcomes of primary bypass surgery and bypass surgery after endovascular treatment in patients with peripheral artery disease. Abstracts and full-text studies were screened independently using duplicate data abstraction. Dichotomous outcome measures were reported using a random-effects model to generate a summary odds ratio (OR) and 95% confidence interval (CI). The risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Seventeen retrospective observational studies were selected from 3911 articles and included 8064 patients, 6252 of whom underwent primary bypass surgery and 1812 underwent bypass surgery after endovascular treatment. The mean age was 69.0 years and 61.2% (n = 4938) were male. For perioperative outcomes, the 30-day results showed no difference in mortality (OR, 0.76; 95% CI, 0.53-1.10), or amputation (OR, 0.89; 95% CI, 0.67-1.20). For short- to mid-term outcomes, primary patency did not differ at 6 months (OR, 0.98; 95% CI, 0.81-1.19), 1 year (OR, 1.12; 95% CI, 0.97-1.30), or 2 years (OR, 1.17; 95% CI, 0.85-1.61) follow-up. Amputation-free survival did not differ at 6 months (OR, 1.03; 95% CI, 0.82-1.30), 1 year (OR, 1.09; 95% CI, 0.89-1.32), 2 years (OR, 1.18; 95% CI, 0.93-1.50), or 3 years (OR, 1.09; 95% CI, 0.84-1.40) of follow-up. No significant difference was found in overall survival or second patency. CONCLUSIONS: This meta-analysis of retrospective, nonrandomized, observational studies suggests that prior endovascular treatment of lower extremity arterial disease does not result in worse perioperative, short-term, or mid-term clinical outcomes of subsequent infrainguinal bypass surgery compared with patients without prior endovascular treatment.

Abdominal Penetrating Aortic Ulcer and Endovascular Treatments: A Systematic Review and Meta-Analysis.

BACKGROUND: Abdominal penetrating aortic ulcer (aPAU) is defined as an ulceration of the aortic intima and media lamina, even with rupture of the internal elastic lamina. Recently, there have been an increasing number of publications on endovascular treatment for aPAU. This review aimed to assess the efficacy and safety of endovascular treatment and provide clinicians with the latest evidence-based medical data. METHODS: 3 academic databases (Embase, PubMed, and Scopus) were systematically searched for literature reporting on aPAU from 1986 (the earliest appearance of the concept of aPAU) to September 1, 2021, and related data were collected and evaluated. A fixed/random effects model was used to construct the forest plots. Funnel plots and linear regression tests were used to assess the publication bias. RESULTS: 6 articles including 121 patients were included in the analysis. The average age was 71.4 years, with 72.7% of males and 85.6% with hypertension. Saccular aneurysms (SA) were the most prevalent complication (35.5%). Endovascular treatment had a perioperative mortality rate of .24% (95% CI, .00-2.70). The technical success rate was 99.15% (95% CI, 96.49-100). The type-II endoleak rate was 5.69% (95% CI, .00-12.13). The 1-year survival rate was 95.69% (95% CI, 90.49-100). The revascularization rate was 7.20% (95% CI, .07-14.32). Endovascular treatments for aPAU would lead to a high rate of technical success, few complications, and satisfactory 1-year survival. CONCLUSIONS: aPAU are a common disease that mainly affects elderly males with hypertension and hyperlipidemia. Endovascular treatment is required when an ulcer progresses rapidly or manifests symptoms. Endovascular treatment is associated with high technical success, low complication, and satisfactory 1-year survival. Further investigation into the long-term results of endovascular treatment is necessary.

Acute Renal Infarction Due to Symptomatic Isolated Spontaneous Renal Artery Dissection: A Rare and Fatal Disease.

OBJECTIVE: To report demographics and clinical, laboratory, and imaging features of acute renal infarction (ARI) due to symptomatic isolated spontaneous renal artery dissection (SISRAD) and to analyze outcomes after the initial therapy for SISRAD. METHODS: Thirteen patients with ARI due to SISRAD between January 2016 and March 2021 were enrolled in this retrospective study. We reviewed the demographics, clinical, laboratory, and imaging features (location of the infarct kidney, the branch artery involved by dissection, true lumen stenosis, false lumen thrombosis, and aneurysm), treatment modalities, and follow-up results; analyzed the difference between SISRAD and other causes of ARI; and propose an appropriate therapy strategy for SISRAD based on our data and literature. RESULT: Patients with ARI due to SISRAD were mostly young men (43 [24-53] years; 12/13 [92%]). No patients had atrial fibrillation or acute kidney injury at admission (0/13). All 13 patients received conservative treatment as the initial treatment. Sixty-two percent (8/13) of patients progressed, and 88% (7/8) of them had dissection aneurysm on the admission computed tomographic angiography (CTA) image. Seventy-five percent (6/8) of patients underwent endovascular intervention as follows, stent placement in 1 patient, renal artery embolization in 1, and stent placement with embolization in 4. Two patients with disease progression died: 1 during the conservative treatment period and 1 after the stent placement. Thirty-eight percent (5/13) of patients in remission continued to receive conservative treatment, none of whom had dissection aneurysm on the admission CTA. CONCLUSION: Symptomatic isolated spontaneous renal artery dissection is a rare and fatal disease. For young ARI patients with no previous history of tumors and cardiogenic diseases, CTA examination is recommended to exclude SISRAD. Dissection aneurysm seems to be a risk of progression for SISRAD in this series. Conservative treatment, a recognized initial treatment, has a good effect on patients without dissection aneurysm, and we recommend endovascular intervention as the initial treatment for the patient with dissection aneurysm at admission. Multicenter clinical studies are needed to explore a more-appropriate treatment for patients with SISRAD. CLINICAL IMPACT: This article report the related factors, risks, demographics and laboratory data of Acute renal infarction (ARI) due to Symptomatic isolated spontaneous renal artery dissection (SISRAD) and explore a better initial therapy strategy for SISRAD. It will help improve the effectiveness of SISRAD treatment and reduce the mortality rate from this rare but lethal disease.

Staphylococcus aureus ST1 promotes persistent urinary tract infection by highly expressing the urease.

Staphylococcus aureus (SA) is a relatively uncommon cause of urinary tract infections (UTIs) in the general population. Although rare, S. aureus-induced UTIs are prone to potentially life-threatening invasive infections such as bacteremia. To investigate the molecular epidemiology, phenotypic characteristics, and pathophysiology of S. aureus-induced UTIs, we analyzed non-repetitive 4,405 S. aureus isolates collected from various clinical sources from 2008 to 2020 from a general hospital in Shanghai, China. Among these, 193 isolates (4.38%) were cultivated from the midstream urine specimens. Epidemiological analysis showed UTI-derived ST1 (UTI-ST1) and UTI-ST5 are the primary sequence types of UTI-SA. Furthermore, we randomly selected 10 isolates from each of the UTI-ST1, non-UTI-ST1 (nUTI-ST1), and UTI-ST5 groups to characterize their in vitro and in vivo phenotypes. The in vitro phenotypic assays revealed that UTI-ST1 exhibits an obvious decline in hemolysis of human red blood cells and increased biofilm and adhesion in the urea-supplemented medium, compared to the medium without urea, while UTI-ST5 and nUTI-ST1 did not show significant differences between the biofilm-forming and adhesion abilities. In addition, the UTI-ST1 displayed intense urease activities by highly expressing urease genes, indicating the potential role of urease in UTI-ST1 survival and persistence. Furthermore, in vitro virulence assays using the UTI-ST1 ureC mutant showed no significant difference in the hemolytic and biofilm-forming phenotypes in the presence or absence of urea in the tryptic soy broth (TSB) medium. The in vivo UTI model also showed that the CFU of the UTI-ST1 ureC mutant rapidly reduced during UTI pathogenesis 72 h post-infection, while UTI-ST1 and UTI-ST5 persisted in the urine of the infected mice. Furthermore, the phenotypes and the urease expression of UTI-ST1 were found to be potentially regulated by the Agr system with the change in environmental pH. In summary, our results provide important insights into the role of urease in S. aureus-induced UTI pathogenesis in promoting bacterial persistence in the nutrient-limiting urinary microenvironment.

Host Sorbitol and Bacterial Sorbitol Utilization Promote Clostridioides difficile Infection in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a widespread gastrointestinal inflammatory disorder with globally increasing incidence. Clostridioides difficile infection (CDI) often occurs in patients with intestinal dysbiosis, such as after antibiotic therapy. Patients with IBD have increased incidence of CDI and the clinical outcome of IBD is reportedly worsened by CDI. However, the underlying reasons remain poorly understood. METHODS: We performed a retrospective single-center and a prospective multicenter analysis of CDI in patients with IBD, including genetic typing of C difficile isolates. Furthermore, we performed a CDI mouse model to analyze the role of the sorbitol metabolization locus that we found distinguished the main IBD- and non-IBD-associated sequence types (STs). Moreover, we analyzed sorbitol concentration in the feces of patients with IBD and healthy individuals. RESULTS: We detected a significant association of specific lineages with IBD, particularly increased abundance of ST54. We found that in contrast to the otherwise clinically predominant ST81, ST54 harbors a sorbitol metabolization locus and was able to metabolize sorbitol in vitro and in vivo. Notably, in the mouse model, ST54 pathogenesis was dependent on intestinal inflammation-induced conditions and the presence of sorbitol. Furthermore, we detected significantly increased sorbitol concentrations in the feces of patients with active IBD vs patients in remission or healthy controls. CONCLUSIONS: Sorbitol and sorbitol utilization in the infecting C difficile strain play major roles for the pathogenesis and epidemiology of CDI in patients with IBD. CDI in patients with IBD may thus be avoided or improved by elimination of dietary sorbitol or suppression of host-derived sorbitol production.

Targeting neuropilin-1 abolishes anti-PD-1-upregulated regulatory T cells and synergizes with 4-1BB agonist for liver cancer treatment.

BACKGROUND AIMS: Regulatory T cells (Tregs) are an obstacle to PD-1 blockade-mediated antitumor efficacy. However, the behaviors of Tregs response to anti-PD-1 in HCC and the characteristics of Tregs tissue adaptation from peripheral lymphoid tissues to the tumor are still unclear. APPROACH RESULTS: Here, we determine that PD-1 monotherapy potentially augments the accumulation of tumor CD4 + Tregs. Mechanistically, anti-PD-1 mediates Tregs proliferation in lymphoid tissues rather than in the tumor. Increased peripheral Tregs burden replenishes intratumoral Tregs, raising the ratio of intratumoral CD4 + Tregs to CD8 + T cells. Subsequently, single-cell transcriptomics revealed that neuropilin-1 (Nrp-1) supports Tregs migration behavior, and the genes of Crem and Tnfrsf9 regulate the behaviors of the terminal suppressive Tregs. Nrp-1 + 4-1BB - Tregs stepwise develop to the Nrp-1 - 4-1BB + Tregs from lymphoid tissues into the tumor. Moreover, Treg-restricted Nrp1 depletion abolishes anti-PD-1-upregulated intratumoral Tregs burden and synergizes with the 4-1BB agonist to enhance the antitumor response. Finally, a combination of the Nrp-1 inhibitor and the 4-1BB agonist in humanized HCC models showed a favorable and safe outcome and evoked the antitumor effect of the PD-1 blockade. CONCLUSION: Our findings elucidate the potential mechanism of anti-PD-1-mediated intratumoral Tregs accumulation in HCC and uncover the tissue adaptation characteristics of Tregs and identify the therapeutic potential of targeting Nrp-1 and 4-1BB for reprogramming the HCC microenvironment.

Novel imaging methods and force probes for molecular mechanobiology of cytoskeleton and adhesion.

Detection and conversion of mechanical forces into biochemical signals is known as mechanotransduction. From cells to tissues, mechanotransduction regulates migration, proliferation, and differentiation in processes such as immune responses, development, and cancer progression. Mechanosensitive structures such as integrin adhesions, the actin cortex, ion channels, caveolae, and the nucleus sense and transmit forces. In vitro approaches showed that mechanosensing is based on force-dependent protein deformations and reorganizations. However, the mechanisms in cells remained unclear since cell imaging techniques lacked molecular resolution. Thanks to recent developments in super-resolution microscopy (SRM) and molecular force sensors, it is possible to obtain molecular insight of mechanosensing in live cells. We discuss how understanding of molecular mechanotransduction was revolutionized by these innovative approaches, focusing on integrin adhesions, actin structures, and the plasma membrane.

[Transcriptional analysis of grape in response to weak light stress].

Grape (Vitis vinifera L.) in production is frequently exposed to inadequate light, which significantly affects its agronomic traits via inhibiting their physiological, metabolic and developmental processes. To explore the mechanism how the grape plants respond to the weak light stress, we used 'Yinhong' grape and examined their physiology-biochemistry characteristics and transcriptional profile under different levels of weak light stress. The results showed that grape seedlings upon low intensity shading treatments were not significantly affected. As the shading stress intensity was strengthened, the epidermis cells, palisade tissue, and spongy tissue in the leaves were thinner, the intercellular space between the palisade tissue and spongy tissue was larger compared with that of the control, and the activities of superoxide dismutase, catalase and peroxidase were decreased gradually. Additionally, the soluble protein content increased and the free proline content decreased gradually. Compared with the control, significant changes in plant photosynthetic characteristics and physiology-biochemistry characteristics were observed under high intensity of shading (80%). RNA-seq data showed that the differentially expressed genes between CK and T2, CK and T4, T2 and T4 were 13 913, 13 293 and 14 943, respectively. Most of the enrichment pathways were closely related with the plant's response to stress. Several signaling pathways in response to stress-resistance, e.g. JA/MYC2 pathway and MAPK signal pathway, were activated under weak light stress. The expression level of a variety of genes related to antioxidation (such as polyphenol oxidase and thioredoxin), photosynthesis (such as phytochrome) was altered under weak light stress, indicating that 'Yinhong' grape may activate the antioxidation related pathways to cope with reactive oxygen species (ROS). In addition, it may activate the expression of photosynthetic pigment and light reaction structural protein to maintain the photosynthesis activity. This research may help better understand the relevant physiological response mechanism and facilitate cultivation of grape seedlings under weak light.

Janus Carbon Nanotube@poly(butylene adipate-co-terephthalate) Fabric for Stable and Efficient Solar-Driven Interfacial Evaporation.

Solar-driven seawater desalination is considered a promising method for alleviating the water crisis worldwide. In recent years, significant efforts have been undertaken to optimize heat management and minimize salt blockage during solar-driven seawater desalination. However, it remains challenging to achieve an efficient and stable seawater evaporator simply and practically. Here, we designed and prepared a novel three-dimensional (3D) water channel evaporator (3D WCE) equipped with a Janus CNT@PBAT fabric (JCPF). The as-prepared Janus CNT@PBAT fabric has broad-band light absorption (∼97.8%), excellent superhydrophobicity (∼162°), and photothermal properties. After optimizing the structure of the thermal insulator, our designed evaporator could realize the equilibrium between enhanced thermal management and sufficient water supply. As a result, the as-prepared evaporator achieved an excellent evaporation rate of 1.576 kg·m-2·h-1 and an energy efficiency of over 92.7% under 1 sun irradiation in 3.5 wt % saline water. Moreover, this evaporator also revealed good salt rejection performance compared to the traditional two-dimensional (2D) water channel evaporator (2D WCE) in high saline water, which could maintain stable evaporation rates under long-term evaporation of 8 h. Our study may develop a simple method for the design and fabrication of a low-cost, effective, and stable solar-driven evaporator for seawater desalination.

Mechanisms of high-level fosfomycin resistance in Staphylococcus aureus epidemic lineage ST5.

OBJECTIVES: Fosfomycin resistance has become a clinical concern. In this study, we analysed the dynamic change of fosfomycin MIC in the epidemic Staphylococcus aureus lineages in a teaching hospital in Shanghai for 12 years and sought to elucidate the major underlying mechanisms. METHODS: MLST was conducted for 4580 S. aureus isolates recovered from 2008 to 2019. Fosfomycin MIC was determined by the agar dilution method. The genome data of 230 S. aureus epidemic lineage isolates were acquired from a next-generation sequencing (NGS) platform. Gene deletion and corresponding complementation mutants were constructed to confirm the mechanism of fosfomycin resistance. RESULTS: The predominant S. aureus lineages during the past 12 years were ST5 and ST239 (45.6%; 2090/4580). However, ST5 has been spreading clinically, while ST239 has gradually disappeared recently. Consistent with epidemic trends, fosfomycin-resistant ST5 increased from 19.5% to 67.3%. Most fosfomycin-resistant ST5 isolates (92.7%; 647/698) possessed high-level resistance (MIC > 1024 mg/L) with combined mutations mainly in glpT and uhpT. In contrast, fosfomycin-resistant ST239 isolates (76.8%; 149/194) mainly acquired low-level resistance (MIC = 64-128 mg/L) with mutation primarily in hptA. Deletion of a single resistant gene merely resulted in low-level fosfomycin resistance, while double-gene mutants ΔglpTΔuhpT, ΔglpTΔhptA and ΔglpTΔhptR acquired high-level fosfomycin resistance. CONCLUSIONS: The high-level fosfomycin resistance of S. aureus epidemic lineage ST5 is mainly due to the accumulation of mutations in the resistant genes related to membrane transporter systems, and partly contributes to its persistent prevalence under clinical antibiotic pressure.

Mid-term Results of the Treatment of Isolated Dissection of the Celiac Artery: A Comparative Analysis of Endovascular Versus Conservative Therapy.

OBJECTIVES: Endovascular treatment (EVT) is an alternative method used to treat isolated dissection of the celiac artery (IDCA). However, only a few mid-term results have been reported. This study aimed to analyze and compare the outcomes of endovascular and non-operative therapies for IDCA. METHODS: Data from a cohort of consecutive IDCA patients enrolled in the study hospital between April 2012 and September 2020 were retrospectively reviewed. Demographic information, imaging features, treatment modalities, and follow-up results of celiac artery remodeling and adverse events were collected and analyzed. RESULTS: A total of 87 patients were enrolled in the study. Stents were deployed in 68 patients, and non-operative treatment (blood pressure control and pain management) was continued in the remaining 19 patients who did not receive stenting; among these 19 patients, EVT failed in 6. The mean follow-up period was 37.3 (range, 10-85 months) and 44.0 (range, 9-80 months) months in the EVT and non-operative groups, respectively. During follow-up, the overall complete remodeling (absence of residual dissection with no false lumen or no intramural thrombus) rate was significantly higher in the EVT group than in the non-operative group (87.3% vs 7.1%, p<0.001). The incomplete remodeling (improved true lumen with malabsorption or partial thrombosis of the false lumen) rate was not significantly different between the EVT and non-operative groups (6.3% vs 14.3%; p=0.2984). Meanwhile, the adverse event-free survival rates were 89.0%, 67.0%, and 67.0% at 1, 3, and 5 years, respectively, in the EVT group compared with 39.7% and 29.8% at 1 and 3 years in the non-operative group (p<0.0001). CONCLUSIONS: EVT for IDCA may be considered an effective management option with a favorable clinical success rate, an encouraging complete remodeling rate, and a satisfactory adverse event-free survival rate. However, further evaluation with a long-term follow-up is required. CLINICAL IMPACT: Endovascular intervention for isolated dissection of the celiac artery has attracted inadequate attention. In this retrospective study with comparative analysis of endovascular versus conservative therapy for isolated dissection of the celiac artery patients, a better complete remodeling rate and a higher adverse event-free survival rate were observed in the endovascular treatment (EVT) group during follow-up, indicating that EVT could be an effective management option for isolated dissection of the celiac artery.

Blocking CD47 promotes antitumour immunity through CD103+ dendritic cell-NK cell axis in murine hepatocellular carcinoma model.

BACKGROUND & AIMS: The CD47-signal regulatory protein α (SIRPα) axis inhibits dendritic cell (DC) phagocytosis and contributes to immune evasion. However, the behaviour of DCs and the potential crosstalk between DCs and natural killer (NK) cells in the hepatocellular carcinoma (HCC) microenvironment after CD47 blockade remain unclear. METHODS: The infiltration of CD103+ DCs and NK cells were analysed by immunohistochemistry and immunofluorescence in both human and murine HCC specimens. An orthotopic liver tumour model was used to evaluate the function of the CD103+ DC-NK cell axis after CD47 blockade in vivo in wild-type, Rag1-/-, Batf3-/-, and STING1-/- mice. Phagocytosis assays were performed in CD103+ DC and HCC cell lines. CD103+ DC-derived cytokines were analysed by chemokine array. Spleen-derived NK cells in C57BL/6J mice were used to evaluate cytotoxic functions in vitro. RESULTS: Higher CD47 expression was associated with worse prognosis in patients with HCC. CD47 blockade enhanced antitumour efficacy by stimulating the CD103+ DC-NK cell axis. The hypoxic microenvironment promoted CD47 blockade-induced tumour DNA phagocytosis by CD103+ DCs. By releasing IL-12 and CXCL9, activated CD103+ DCs induced the recruitment of NK cells with upregulated expression of granzyme B, NKG2D, interferon-γ, and tumour necrosis factor-α and downregulated expression of NKG2A. The antitumour effects of CD47 blockade could be abolished by cyclic GMP-AMP synthase (cGAS)-STING pathway inhibition. CONCLUSIONS: In addition to the classical DC-T cell axis, CD47 blockade significantly enhanced the ability of CD103+ DCs to take up tumour DNA, resulting in the stimulation of the cGAS-STING pathway, which promoted the infiltration and activation of NK cells in liver cancer. LAY SUMMARY: Hypoxia (low oxygen levels) is prevalent in the hepatocellular carcinoma microenvironment and promotes the phagocytosis (ingestion and elimination) of tumour DNA by CD103+ dendritic cells (a type of immune cell). Blockade of the cell surface protein CD47 resulted in activation of CD103+ dendritic cells which led to the recruitment and activation of natural killer cells (a different immune cell). When activated, these cells exhibit an antitumour effect.

Essential role of membrane vesicles for biological activity of the bacteriocin micrococcin P1.

Bacterial membrane vesicles (MVs) have recently gained much attention and have been shown to carry a wide diversity of secreted bacterial components. However, it is poorly understood whether MV carriage is an indispensable requirement for a cargo's function. Bacteriocins as weapons of bacterial warfare shape the composition of microbial communities. Many bacteriocins have pronounced hydrophobicity that is imposed by their mechanism of action, but how they diffuse through aqueous environments to reach their target competitors is not known. Here we show that antimicrobial competitive activity of an exemplary hydrophobic bacteriocin of the thiopeptide antibiotic family, micrococcin P1 (MP1), is dependent on incorporation into MVs, which were found to carry MP1 at high concentrations. In contrast, MP1 without MV association was poorly active due to low solubility. Furthermore, we provide previously unavailable evidence that MVs fuse with a Gram-positive bacterium's cytoplasmic membrane, in this case to deliver a bacteriocin to its intracellular target. Our findings demonstrate how bacteria overcome the problem associated with secreting hydrophobic small molecules and delivering them to their target and show that MVs have a key function in bacterial warfare. Furthermore, our study provides hitherto rare evidence that MVs provide an essential rather than merely accessory function in bacterial physiology.

A synthetic distributed genetic multi-bit counter.

A design for genetically encoded counters is proposed via repressor-based circuits. An N-bit counter reads sequences of input pulses and displays the total number of pulses, modulo 2 N . The design is based on distributed computation with specialized cell types allocated to specific tasks. This allows scalability and bypasses constraints on the maximal number of circuit genes per cell due to toxicity or failures due to resource limitations. The design starts with a single-bit counter. The N-bit counter is then obtained by interconnecting (using diffusible chemicals) a set of N single-bit counters and connector modules. An optimization framework is used to determine appropriate gate parameters and to compute bounds on admissible pulse widths and relaxation (inter-pulse) times, as well as to guide the construction of novel gates. This work can be viewed as a step toward obtaining circuits that are capable of finite automaton computation in analogy to digital central processing units.