Multicenter Investigation of Drug-Resistance in Burkholderia Cepacia Bloodstream Infections in Hebei Province, China, from 2016 to 2021.

Objective: To compare the epidemiological characteristics and drug resistance of Burkholderia cepacia isolated from blood cultures, and to provide data support and a scientific basis for the clinical treatment and detection of hospital infections. Methods: The Hebei Province Antimicrobial Surveillance Network received 349 B. cepacia strains isolated from blood cultures reported by 83 hospitals, from 2016 to 2021. These strains were identified by MALDI-TOF MS and, the antibiotic sensitivity tests were carried out using the VITEK 2 COMPACT system. The 2023 Institute of Clinical and Laboratory Standardization drug-susceptibility breakpoints were used for drug susceptibility testing and the data were analyzed using WHONET5.6 software. Results: A total of 349 B. cepacia strains were isolated from 2016 to 2021, including 68 strains from secondary hospitals and 281 strains from tertiary hospitals. The ratios of male: female patients with B. cepacia bloodstream infections in all hospitals, secondary hospitals, and tertiary hospitals were 1.49:1 (209/140), 2.09:1 (46/22), and 1.38:1 (163/118), respectively. Most B. cepacia strains were isolated in intensive care units (ICUs), followed by internal medicine departments, accounting for 49.57% (173/349) and 22.92% (80/349), respectively. Regarding the age distribution, most patients were elderly (>65 years, 57.59%, 201/349), with numbers of patients gradually declining with decreasing of age. The resistance rates for levofloxacin, ceftazidime, and sulfamethoxazole decreased over the 6-year period (P<0.05), while there were no significant changes in the resistance rates for meropenem, chloramphenicol, and minocycline (P>0.05). There was no significant difference in drug-resistance rates between secondary and tertiary hospitals (P>0.05). Conclusion: Attention should be paid to bloodstream infections caused by B. cepacia, especially elderly patients and patients admitted to the ICU. The difficult treatment characteristics of B. cepacia bloodstream infections mean that laboratories and clinicians should pay careful attention to drug resistance to provide a basis for their prevention and empirical treatment.

p97 inhibits integrated stress response-induced neuronal apoptosis after subarachnoid hemorrhage in mice by enhancing proteasome function.

Neuronal apoptosis is a common pathological change in early brain injury after subarachnoid hemorrhage (SAH), and it is closely associated with neurological deficits. According to previous research, p97 exhibits a remarkable anti-cardiomyocyte apoptosis effect. p97 is a critical molecule in the growth and development of the nervous system. However, it remains unknown whether p97 can exert an anti-neuronal apoptosis effect in SAH. In the present study, we examined the role of p97 in neuronal apoptosis induced after SAH and investigated the underlying mechanism. We established an in vivo SAH mice model and overexpressed the p97 protein through transfection of the mouse cerebral cortex. We analyzed the protective effect of p97 on neurons and evaluated short-term and long-term neurobehavior in mice after SAH. p97 was found to be significantly downregulated in the cerebral cortex of the affected side in mice after SAH. The site showing reduced p97 expression also exhibited a high level of neuronal apoptosis. Adeno-associated virus-mediated overexpression of p97 significantly reduced the extent of neuronal apoptosis, improved early and long-term neurological function, and repaired the neuronal damage in the long term. These neuroprotective effects were accompanied by enhanced proteasome function and inhibition of the integrated stress response (ISR) apoptotic pathway involving eIF2α/CHOP. The administration of the p97 inhibitor NMS-873 induced a contradictory effect. Subsequently, we observed that inhibiting the function of the proteasome with the proteasome inhibitor PS-341 blocked the anti-neuronal apoptosis effect of p97 and enhanced the activation of the ISR apoptotic pathway. However, the detrimental effects of NMS-873 and PS-341 in mice with SAH were mitigated by the administration of the ISR inhibitor ISRIB. These results suggest that p97 can promote neuronal survival and improve neurological function in mice after SAH. The anti-neuronal apoptosis effect of p97 is achieved by enhancing proteasome function and inhibiting the overactivation of the ISR apoptotic pathway.

Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway.

Colorectal cancer (CRC) is the third most common tumor, with an increasing number of deaths worldwide each year. Tremendous advances in the diagnosis and treatment of CRC have significantly improved the outcomes for CRC patients. Additionally, accumulating evidence has hinted the relationship between acidic nuclear phosphoprotein 32 family member E (ANP32E) and cancer progression. But the role of ANP32E in CRC remains unclear. In our study, through TCGA database, it was demonstrated that the expression of ANP32E was enhanced in COAD tissues (n = 286). In addition, the mRNA and protein expression of ANP32E was also confirmed to be upregulated in CRC cell lines. Further investigation uncovered that knockdown of ANP32E suppressed cell proliferation and glycolysis, and facilitated cell apoptosis in CRC. Moreover, inhibition of ANP32E inhibited the AKT/mTOR pathway. Through rescue assays, we discovered that the reduced cell proliferation, glycolysis and the enhanced cell apoptosis mediated by ANP32E repression was reversed by SC79 treatment. In summary, ANP32E aggravated the growth and glycolysis of CRC cells by stimulating the AKT/mTOR pathway. This finding suggested that the ANP32E has the potential to be explored as a novel biomarker for CRC treatment.

Design Synthesis of Low-Silica SAPO-34 Nanocrystals by Constructing Isomorphous Core-Shell Structure: An Effective Catalyst for Improving Catalytic Performances in Methanol-to-Olefins Reaction.

It is well known that low-silica SAPO-34, with an extra porosity (meso- and/or macropores) system, affords excellent catalytic performance in the methanol-to-olefins (MTO) reaction, while the direct synthesis of low-silica SAPO-34 with a hierarchical structure is difficult to achieve, principally because the crystal impurities are usually formed under a low silica content in a gel precursor. Herein, low-silica SAPO-34 nanocrystals were successfully fabricated for the first time by constructing an isomorphous core-shell structure in an epitaxial growth manner. In which, low-silica, ultrasmall nanosquare-shaped SAPO-34 crystals with the same growth orientation along the (100) crystal plane compactly grow on the monocrystal SAPO-34 cores. Crucially, the external surface acid properties of the core SAPO-34 with the Si-rich outer layer are effectively modified by the low-silica SAPO-34 shell. Furthermore, the growth process and Si-substitution mechanism of the shell zeolite were comprehensively investigated. It was found that with the prolonged crystallization time, more and more coordinated Si(4Al) and Si(3Al) structures via two substitution mechanisms (SM2 and SM3) are generated in the nanocrystalline SAPO-34 shell, which endow moderate acidity of the core-shell SAPO-34. Compared to the uncoated SAPO-34, the core-shell SAPO-34 performs a longer lifespan and a higher average selectivity of light olefins (ethylene plus propylene) when applied to the MTO reaction, which is attributed to the positive effects of the luxuriant interstitial pores offering a fast diffusion channel and the moderate acid density depressing the hydrogen transfer reaction of light olefins. This work provides new insights into the fabrication of low-silica SAPO-34 nanocrystals, which are based on the rational design of the isomorphous core-shell zeolite.

Classification and hemodynamic characteristics of delayed intracerebral hemorrhage following stent-assisted coil embolism in unruptured intracranial aneurysms.

Background and objective: Stent-assisted coil (SAC) embolization is a commonly used endovascular treatment for unruptured intracranial aneurysms (UIAs) but can be associated with symptomatic delayed intracerebral hemorrhage (DICH). Our study aimed to investigate the hemodynamic risk factors contributing to DICH following SAC embolization and to establish a classification for DICH predicated on hemodynamic profiles. Methods: This retrospective study included patients with UIAs located in the internal carotid artery (ICA) treated with SAC embolization at our institution from January 2021 to January 2022. We focused on eight patients who developed postoperative DICH and matched them with sixteen control patients without DICH. Using computational fluid dynamics, we evaluated the hemodynamic changes in distal arteries [terminal ICA, the anterior cerebral artery (ACA), and middle cerebral artery (MCA)] pre-and post-embolization. We distinguished DICH-related arteries from unrelated ones (ACA or MCA) and compared their hemodynamic alterations. An imbalance index, quantifying the differential in flow velocity changes between ACA and MCA post-embolization, was employed to gauge the flow distribution in distal arteries was used to assess distal arterial flow distribution. Results: We identified two types of DICH based on postoperative flow alterations. In type 1, there was a significant lower in the mean velocity increase rate of the DICH-related artery compared to the unrelated artery (-47.25 ± 3.88% vs. 42.85 ± 3.03%; p < 0.001), whereas, in type 2, there was a notable higher (110.58 ± 9.42% vs. 17.60 ± 4.69%; p < 0.001). Both DICH types demonstrated a higher imbalance index than the control group, suggesting an association between altered distal arterial blood flow distribution and DICH occurrence. Conclusion: DICH in SAC-treated UIAs can manifest as either a lower (type 1) or higher (type 2) in the rate of velocity in DICH-related arteries. An imbalance in distal arterial blood flow distribution appears to be a significant factor in DICH development.

Study of factors affecting the remediation of contaminated soil through pneumatic fracturing and soil vapor extraction.

In low-permeability soils, the effectiveness of soil vapor extraction (SVE) is often constrained, resulting in increased time and operational expenses. In this study, pneumatic fracturing and the SVE were combined to remediate low-permeability clay contaminated with ammonia gas. The soil parameters, pneumatic fracturing parameters, extraction mode, and other influencing factors were investigated via laboratory testing. The results indicated that: (1) Pneumatically induced fracturing disrupts soil structure, forming cracks and providing new pathways for ammonium gas migration; (2) the soil crack area exhibits a quadratic function relationship with both the fracturing pressure and frequency, and the soil crack area increases with higher pneumatic frequencies, leading to a faster pneumatic pressure decline; (3) a denser network of pathways emerges within the soil due to the reduced distance between the two pneumatic fracturing points, consequently enhancing soil permeability and increasing pollutant elimination efficiency; (4) the ammonium gas removal efficiency gradually increases with an increase in the extracted vapor flow rate, but there is an optimal extraction flow rate (9 L/min); (5) continuous extraction combined with gas injection effectively ameliorates the issue of prolonged fluctuations in ammonium gas concentration during the later stages of extraction. (6) Fracturing and extraction reduce the moisture content of the surrounding soil. The results demonstrated the feasibility and superiority of pneumatic pre-fracturing extraction in low-permeability soils.

Pancoronary plaque characteristics in STEMI patients with rapid plaque progression: An optical coherence tomography study.

BACKGROUND: Non-culprit plaque progression is associated with recurrent cardiac ischemic events and worse clinical outcomes. Given that atherosclerosis is a systemic disease, the pancoronary characteristics of patients with rapid plaque progression are unknown. This study aims to identify pancoronary plaque features in patients with ST-segment elevation myocardial infarction (STEMI) with and without rapid plaque progression, focused on the patient level. METHODS AND RESULTS: From January 2017 to July 2019, 291 patients underwent 3-vessel optical coherence tomography imaging at the time of the primary procedure and a follow-up angiography interval of 12 months. The final analysis included 237 patients. Overall, 308 non-culprit lesions were found in 78 STEMI patients with rapid plaque progression, and 465 non-culprit plaques were found in 159 STEMI patients without rapid plaque progression. These patients had a higher pancoronary vulnerability (CLIMA-defined high-risk plaque: 47.4% vs. 33.3%; non-culprit plaque rupture: 25.6% vs. 14.5%) and a significantly higher prevalence of other vulnerable plaque characteristics (i.e., lipid-rich plaque, cholesterol crystal, microchannels, calcification, spotty calcification, and thrombus) at baseline versus those without rapid plaque progression. Lesions with rapid progression were highly distributed at the LAD, tending to be near the bifurcation. In multivariate analysis, age ≥ 65 years was an independent predictor of subsequent rapid lesion progression at the patient level, whereas microchannel, spotty calcification, and cholesterol crystal were independent predictors for STEMI patients ≥65 years old. CONCLUSIONS: STEMI patients with subsequent rapid plaque progression had higher pancoronary vulnerability and commonly presented vulnerable plaque morphology. Aging was the only predictor of subsequent rapid plaque progression.

Connexin 36 Mediated Intercellular Endoplasmic Reticulum Stress Transmission Induces SSTA Resistance in Growth Hormone Pituitary Adenoma.

Somatostatin analogues (SSTA) are first-line pharmacological treatment choice for acromegaly, which received satisfying tumor shrinkage and normalization of growth hormone. However, there are still patients unresponsive to SSTA, and the underline mechanism remains unknown. Besides, there is no evidence regarding the role of endoplasmic reticulum stress (ERS) and its transmission in SSTA resistance, which also require investigation. Primary growth hormone adenoma cells and cell lines were treated with SSTA; autophagy double-labeled LC3 (mRFP-GFP) adenovirus transfection, flow cytometry sorting, western blotting, calcium imaging as well as immunofluorescence staining were used to determine ERS and autophagy signal transmission; xenograft and syngeneic tumor in vivo model were exploited to confirm the ERS signal transmission mediated effect. Our results revealed that SSTA induces ERS in pituitary growth hormone (GH) adenoma cells. The ERS signals can be intercellularly transmitted, leading to less responsible to SSTA treatment. Moreover, SSTA stimulates inositol triphosphate (IP3) elevation, mediating ERS intercellular transfer. In addition, connexin 36 tunnels ERS transmission, and its blocker, Quinine, exhibits a synergistic effect with SSTA treating GH adenoma. Our study provided insight into ERS intercellular transmission mediated SSTA resistance, which could be translated into clinical usage to improve SSTA efficiency in GH adenoma treatment.

GSK-3ß activation mediates apolipoprotein E4-associated cognitive impairment in type 2 diabetes mellitus: A multicenter, cross-sectional study.

AIM: Both the activation of glycogen synthase kinase-3ß (GSK-3ß) and the presence of ApoE ε4 genotype have been found to respectively correlate with cognitive decline in patients with type 2 diabetes mellitus (T2DM), who further show a high incidence of developing Alzheimer's disease. However, the relationship between ApoE ε4 and GSK-3ß in the cognitive impairment of T2DM patients remains unclear. METHODS: ApoE genotypes and platelet GSK-3ß level were measured in 1139 T2DM patients recruited from five medical centers in Wuhan, China. Cognitive functions were assessed by Mini-Mental State Examination (MMSE). The association and the relationships among apolipoprotein E (ApoE) genotypes, GSK-3ß activity and cognitive function were analyzed by regression and mediating effect analyses, respectively. RESULTS: T2DM patients with ApoE ε4 but not ApoE ε2 haplotype showed poorer cognitive function and elevated platelet GSK-3ß activity, when using ApoE ε3 as reference. The elevation of GSK-3ß activity was positively correlated the diabetes duration, as well as plasma glycated hemoglobin (HbA1c) and glucose levels. Moreover, correlation and regression analysis also revealed significant pairwise correlations among GSK-3ß activity, ApoE gene polymorphism and cognitive function. Lastly, using Baron and Kenny modeling, we unveiled a mediative role of GSK-3ß activity between ApoE ε4 and cognitive impairment. CONCLUSION: We reported here that the upregulation of GSK-3ß activity mediates the exacerbation of cognitive impairment by ApoE ε4-enhanced cognitive impairment in T2DM patients, suggesting GSK-3ß inhibitors as promising drugs for preserving cognitive function in T2DM patients, especially to those with ApoE ε4 genotype.

A disintegrin and metalloproteinase 22 activates integrin ß1 through its disintegrin domain to promote the progression of pituitary adenoma.

BACKGROUND: Approximately 35% of pituitary adenoma (PA) display an aggressive profile, resulting in low surgical total resection rates, high recurrence rates, and worse prognosis. However, the molecular mechanism of PA invasion remains poorly understood. Although "a disintegrin and metalloproteinases" (ADAMs) are associated with the progression of many tumors, there are no reports on ADAM22 in PA. METHODS: PA transcriptomics databases and clinical specimens were used to analyze the expression of ADAM22. PA cell lines overexpressing wild-type ADAM22, the point mutation ADAM22, the mutated ADAM22 without disintegrin domain, and knocking down ADAM22 were generated. Cell proliferation/invasion assays, flow cytometry, immunohistochemistry, immunofluorescence, co-immunoprecipitation, mass spectrometry, Reverse transcription-quantitative real-time PCR, phos-tag SDS-PAGE, and Western blot were performed for function and mechanism research. Nude mice xenograft models and rat prolactinoma orthotopic models were used to validate in vitro findings. RESULTS: ADAM22 was significantly overexpressed in PA and could promote the proliferation, migration, and invasion of PA cells. ADAM22 interacted with integrin ß1 (ITGB1) and activated FAK/PI3K and FAK/ERK signaling pathways through its disintegrin domain to promote PA progression. ADAM22 was phosphorylated by PKA and recruited 14-3-3, thereby delaying its degradation. ITGB1-targeted inhibitor (anti-itgb1) exerted antitumor effects and synergistic effects in combination with somatostatin analogs or dopamine agonists in treating PA. CONCLUSIONS: ADAM22 was upregulated in PA and was able to promote PA proliferation, migration, and invasion by activating ITGB1 signaling. PKA may regulate the degradation of ADAM22 through post-transcriptional modification levels. ITGB1 may be a potential therapeutic target for PA.

Effect of two different crystal forms of alumina on hydration properties and mechanical properties of steel slag-cement composite cementitious materials.

In the present work, two common nano-alumina (NA) with different crystal forms (α-NA and γ-NA) are used to research the effects of steel slag-cement composite cementitious materials, which include the hydration properties and mechanical properties. The results show that the NA can enhance the strength of steel slag-cement composite cementitious materials, especially the early strength. Meanwhile, when the addition amount of γ-NA was 1%, the maximum compressive strength and flexural strength at 28 d were 35.43 and 5.21 MPa, respectively; when the addition amount of α-NA was 3%, the maximum compressive strength and flexural strength at 28 d were 36.27 and 4.89 MPa, respectively. In addition, according to the analysis of X-ray diffractometer and differential thermal analysis, it was concluded that the effects of the two types of alumina on the strength were mainly pozzolanic effect and filling effect. The pozzolanic effect of γ-NA was significantly stronger than that of α-NA. However, the large surface area of γ-NA affected the dispersion of the particles and the filling effect. According to scanning electron microscope analysis, compared with α-NA, γ-NA had significantly more hydration products and tighter adhesion. In conclusion, the addition of NA not only improved the properties but further realized the value-added utilization of steel slag.

CypD induced ROS output promotes intracranial aneurysm formation and rupture by 8-OHdG/NLRP3/MMP9 pathway.

Reactive Oxygen Species (ROS) are widely accepted as a pernicious factor in the progression of intracranial aneurysm (IA), which is eminently related to cell apoptosis and extracellular matrix degradation, but the mechanism remains to be elucidated. Recent evidence has identified that enhancement of Cyclophilin D (CypD) under stress conditions plays a critical role in ROS output, thus accelerating vascular destruction. However, no study has confirmed whether cypD is a detrimental mediator of cell apoptosis and extracellular matrix degradation in the setting of IA development. Our data indicated that endogenous cypD mRNA was significantly upregulated in human IA lesions and mouse IA wall, accompanied by higher level of ROS, MMPs and cell apoptosis. CypD-/- remarkably reversed vascular smooth muscle cells (VSMCs) apoptosis and elastic fiber degradation, and significantly decreased the incidence of aneurysm and ruptured aneurysm, together with the downregulation of ROS, 8-OHdG, NLRP3 and MMP9 in vivo and vitro. Furthermore, we demonstrated that blockade of cypD with CsA inhibited the above processes, thus preventing IA formation and rupture, these effects were highly dependent on ROS output. Mechanistically, we found that cypD directly interacts with ATP5B to promote ROS release in VSMCs, and 8-OHdG directly bind to NLRP3, which interacted with MMP9 to increased MMP9 level and activity in vivo and vitro. Our data expound an unexpected role of cypD in IA pathogenesis and an undescribed 8-OHdG/NLRP3/MMP9 pathway involved in accelerating VSMCs apoptosis and elastic fiber degradation. Repressing ROS output by CypD inhibition may be a promising therapeutic strategy for prevention IA development.

Local transplantation of mesenchymal stem cells improves encephalo-myo-synangiosis-mediated collateral neovascularization in chronic brain ischemia.

BACKGROUND: To explore whether local transplantation of mesenchymal stem cells (MSCs) in temporal muscle can promote collateral angiogenesis and to analyze its main mechanisms of promoting angiogenesis. METHODS: Bilateral carotid artery stenosis (BCAS) treated mice were administrated with encephalo-myo-synangiosis (EMS), and bone marrow mesenchymal stem cells (BMSCs) were transplanted into the temporal muscle near the cerebral cortex. On the 30th day after EMS, the Morris water maze, immunofluorescence, laser speckle imaging, and light sheet microscopy were performed to evaluate angiogenesis; In addition, rats with bilateral common carotid artery occlusion were also followed by EMS surgery, and BMSCs from GFP reporter rats were transplanted into the temporal muscle to observe the survival time of BMSCs. Then, the concentrated BMSC-derived conditioned medium (BMSC-CM) was used to stimulate HUVECs and BMECs for ki-67 immunocytochemistry, CCK-8, transwell and chick chorioallantoic membrane assays. Finally, the cortical tissue near the temporal muscle was extracted after EMS, and proteome profiler (angiogenesis array) as well as RT-qPCR of mRNA or miRNA was performed. RESULTS: The results of the Morris water maze 30 days after BMSC transplantation in BCAS mice during the EMS operation, showed that the cognitive impairment in the BCAS + EMS + BMSC group was alleviated (P < 0.05). The results of immunofluorescence, laser speckle imaging, and light sheet microscopy showed that the number of blood vessels, blood flow and astrocytes increased in the BCAS + EMS + BMSC group (P < 0.05). The BMSCs of GFP reporter rats were applied to EMS and showed that the transplanted BMSCs could survive for up to 14 days. Then, the results of ki-67 immunocytochemistry, CCK-8 and transwell assays showed that the concentrated BMSC-CM could promote the proliferation and migration of HUVECs and BMECs (P < 0.05). Finally, the results of proteome profiler (angiogenesis array) in the cerebral cortex showed that the several pro-angiogenesis factors (such as MMP-3, MMP-9, IGFBP-2 or IGFBP-3) were notably highly expressed in MSC transplantation group compared to others. CONCLUSIONS: Local MSCs transplantation together with EMS surgery can promote angiogenesis and cognitive behavior in chronic brain ischemia mice. Our study illustrated that MSC local transplantation can be the potential therapeutical option for improving EMS treatment efficiency which might be translated into clinical application.

A Mendelian randomisation, propensity score matching study to investigate causal association between serum homocysteine and intracranial aneurysm.

BACKGROUND AND PURPOSE: Recent observational studies have reported that serum total homocysteine (tHcy) is associated with intracranial aneurysms (IAs). However, the causal effect of tHcy on IAs is unknown. We leveraged large-scale genetic association and real-world data to investigate the causal effect of tHcy on IA formation. METHODS: We performed a two-sample Mendelian randomisation (MR) using publicly available genome-wide association studies summary statistics to investigate the causal relationship between tHcy and IAs, following the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology-MR statement. Furthermore, a propensity score matching (PSM) analysis was conducted to evaluate the detailed effects of tHcy on risk of IA formation by utilizing real-world multicentre data, including 9902 patients with and without IAs (1:1 matched). Further interaction and subgroup analyses were performed to elucidate how tHcy affects risk of IA formation. RESULTS: MR analyses indicated that genetically determined tHcy was causally associated with IA risk (OR, 1.38, 95% CI 1.07 to 1.79; p=0.018). This is consistent with the more conservative weighted median analysis (OR, 1.41, 95% CI 1.03 to 1.93; p=0.039). Further sensitivity analyses showed no evidence of horizontal pleiotropy or heterogeneity of single nucleotide polymorphisms in causal inference. According to the PSM study, we found that, compared with low tHcy (≤15 µmol/L), moderate tHcy (>15-30 µmol/L) (OR 2.13, 95% CI 1.93 to 2.36) and high tHcy (>30 µmol/L) (OR 3.66, 95% CI 2.71 to 4.95) were associated with a higher IA risk (p trend <0.001). Subgroup analyses demonstrated significant ORs of tHcy in each subgroup when stratified by traditional cardiovascular risk factors. Furthermore, there was also a synergistic effect of tHcy and hypertension on IA risk (p interaction <0.001; the relative excess risk due to interaction=1.65, 95% CI 1.29 to 2.01). CONCLUSION: Both large-scale genetic evidence and multicentre real-world data support a causal association between tHcy and risk of IA formation. Serum tHcy may serve as a biomarker to identify high-risk individuals who would particularly benefit from folate supplementation.

Tumor-Associated Fibroblast-Derived Exosomal circDennd1b Promotes Pituitary Adenoma Progression by Modulating the miR-145-5p/ONECUT2 Axis and Activating the MAPK Pathway.

TAF participated in the progression of various cancers, including PA via the release of soluble factors. Exosomes belonged to extracellular vesicles, which were revealed as a crucial participator in intercellular communication. However, the expression pattern and effect of TAF-derived exosomes remained largely unknown in PA. In the present study, we performed in silico analysis based on public RNA-seq datasets to generate the circRNA/miRNA regulatory network. The qRT-PCR, Western blotting, RNA pull-down, and luciferase assay were performed to investigate the effect of TAF-derived exosomes. TAF-derived exosomal circDennd1b was significantly upregulated in PA and promoted the proliferation, migration, and invasion of PA cells via sponging miR-145-5p in PA cells. In addition, miR-145-5p directly regulated One Cut homeobox 2 (ONECUT2/OC2) expression and inhibited the promoting effect of ONECUT2 on PA. We further demonstrated that ONECUT2 transcriptionally increased fibroblast growth factor receptor 3 (FGFR3) expression, which further activates the mitogen-activated protein kinases (MAPK) pathway, thus promoting PA progression. Moreover, the suppression of TAFs by ABT-263 and ONECUT2 by CSRM617 inhibited the growth of PA. In conclusion, our study illustrated that TAF-derived exosomal circDennd1b affected PA progression via regulating ONECUT2 expression, which provides a potential therapeutic strategy against aggressive PA.

Carbon Nitride-Based siRNA Vectors with Self-Produced O2 Effects for Targeting Combination Therapy of Liver Fibrosis via HIF-1α-Mediated TGF-ß1/Smad Pathway.

Hypoxia is an important feature, which can upregulate the hypoxia-inducible factor-1α (HIF-1α) expression and promote the activation of hepatic stellate cells (HSCs), leading to liver fibrosis. Currently, effective treatment for liver fibrosis is extremely lacking. Herein, a safe and effective method is established to downregulate the expression of HIF-1α in HSCs via targeted delivery of VA-PEG-modified CNs-based nanosheets-encapsulated (VA-PEG-CN@GQDs) HIF-1α small interfering RNA (HIF-1α-siRNA). Due to the presence of lipase in the liver, the reversible release of siRNA can be promoted to complete the transfection process. Simultaneously, VA-PEG-CN@GQD nanosheets enable trigger the water splitting process to produce O2 under near-infrared (NIR) irradiation, thereby improving the hypoxic environment of the liver fibrosis site and maximizing the downregulation of HIF-1α expression to improve the therapeutic effect, as demonstrated in liver fibrosis mice. Such combination therapy can inhibit the activation of HSCs via HIF-1α-mediated TGF-ß1/Smad pathway, achieving outstanding therapeutic effects in liver fibrosis mice. In conclusion, this study proposes a novel strategy for the treatment of liver fibrosis by regulating the hypoxic environment and the expression of HIF-1α at lesion site.

Fabrication of BODIPY/polyvinyl alcohol/alkaline lignin antibacterial composite films for food packing.

Foodborne pathogens seriously endanger people's health and cause significant economic losses. Therefore, it is of great significance to design potent packaging materials with the function of alleviating food spoiling and extending shelf life. Here, three BODIPY derivatives (named as N-BDPI, B-BDPI and P-BDPI) were synthesized by substituting the 8-position of BODIPY with naphthalene, biphenyl and pyridine groups, respectively, and their photophysical properties as well as antibacterial capacities were characterized. The results demonstrated that N-BDPI had the best singlet oxygen generation ability and could completely kill S. aureus under light irradiation with the minimum inhibitory concentration of only 50 nmol/L. In addition, 1.0% BDPI@PVA/AL composite film was fabricated by doping N-BDPI into polyvinyl alcohol (PVA) and alkaline lignin (AL) exhibited high antibacterial activity on Gram-positive bacteria. The coating of strawberries with 1.0% BDPI@PVA/AL film not only effectively inhibited the mildew of strawberries, but also extended their shelf life.

Morphological Characteristics of Culprit Plaques in Acute Myocardial Infarction Patients With Different Scores of Type A Personality　- An Intravascular Optical Coherence Tomography Study.

BACKGROUND: Previous studies have suggested a relationship between type A personality and the occurrence of coronary artery disease, so we used intravascular optical coherence tomography (OCT) to investigate the morphological characteristics of culprit plaques in acute myocardial infarction (AMI) patients with different scores of type A personality.Methods and Results: A total of 221 AMI patients who underwent preintervention imaging of culprit lesions and an assessment of type A behavior pattern were included. According to the scores for the behavior questionnaire, these patients were divided into 3 groups: non-type A personality (n=91), intermediate personality (n=73), and type A personality (n=57). Patients with type A personality were younger (P=0.003) and had a higher level of total cholesterol (P=0.029) and more severe luminal stenosis (P=0.046). In addition, the prevalence of microchannels (P<0.001), macrophage accumulation (P<0.001), and plaque rupture (P=0.010) with greater number (P<0.001), cavity angle (P<0.001), and length (P<0.001) was highest in the type A personality group. CONCLUSIONS: The culprit lesions of AMI patients with increased scores for type A personality had more severe coronary luminal stenosis, and the proportion of vulnerable features was increased.

Bacteremia Caused by a Serotype Ob5 Vibrio cholerae Strain in a Cirrhotic Patient in China.

The increasing incidence of non-O1/non-O139 Vibrio cholerae (NOVC) has been observed worldwide. However, septicemia caused by NOVC remains a rare condition that has received limited attention. Currently, there are no established treatment guidelines for bloodstream infections caused by NOVC, and the understanding of this condition mainly relies on individual case reports. Although NOVC bacteremia can be fatal in a small percentage of cases, knowledge about its microbiological features remains limited. Here, we present a case of V. cholerae septicemia caused by NOVC in a 46-year-old man with chronic viral hepatitis and liver cirrhosis. The isolated strain, named V. cholerae VCH20210731 and classified as a new sequence type (ST), ST1553, was found to be susceptible to most of the antimicrobial agents tested. O-antigen serotyping of V. cholerae VCH20210731 revealed that it belonged to serotype Ob5. Interestingly, the ctxAB genes, which are typically associated with V. cholerae, were absent in VCH20210731. However, the strain possessed 25 other potential virulence genes, such as hlyA, luxS, hap, and rtxA. The resistome of V. cholerae VCH20210731 included several genes, including qnrVC4, crp, almG, and parE. Nevertheless, susceptibility testing demonstrated that the isolate was susceptible to most of the antimicrobial agents tested. Phylogenetic analysis indicated that the closest strain to VCH20210731 was strain 120 from Russia, differing by 630 single-nucleotide polymorphisms (SNPs). Our findings contribute to the understanding of the genomic epidemiological characteristics and antibiotic resistance mechanisms of this invasive bacterial pathogen. IMPORTANCE This study highlights the discovery of a novel ST1553 V. cholerae strain in China, providing valuable insights into the genomic epidemiology and global transmission dynamics of V. cholerae. It is important to note that clinical presentations of NOVC bacteremia can vary significantly, and the isolates demonstrate genetic diversity. Consequently, health care professionals and public health experts should remain vigilant about the potential for infection with this pathogen, particularly considering the elevated prevalence of liver disease in China.

Retrospective Analysis of Sensitivity Characteristics of Enterobacteriaceae: A Study Based on Specimen Types, Sex, and Age Bracket of Patients.

Objective: Enterobacteriaceae have displayed widespread trends of antimicrobial resistance in recent years. Therefore, we aimed to analyse the antimicrobial susceptibility of common bacteria and explore the significance in treatment and research of infections induced by Enterobacteriaceae. Methods: We retrospectively analysed 10,775 antimicrobial susceptibility test results acquired over a 6-year period in the affiliated hospital of Chengde Medical University. We divided the data based on specimen type (blood, sputum, pus, or urine), and population characteristics (age bracket and sex) for analysis. We mainly analysed the antimicrobial susceptibility of Escherichia coli (Eco), Klebsiella pneumoniae (Kpn), and Enterobacter cloacae (Ecl). Results: In our study, it was found that the resistance rates of Eco, Kpn, and Ecl to most antimicrobial agents were significantly different (P < 0.05) on specimen type and age bracket. The Eco from sputum had the highest resistance rates except ciprofloxacin (CIP), levofloxacin (LVX), and gentamicin (GEN); the Kpn from urine had the highest resistance rates to all antimicrobial agents; the Ecl from urine had the highest resistance rates to most antimicrobial agents. The Eco from geriatric patients had the highest resistance rates except GEN and SXT; the Kpn from adult patients had the lowest resistance rates to most antimicrobial agents except LVX. The Eco isolated from males had higher resistance rates to most antimicrobial agents except CIP, LVX, and NIT than those isolated from females; the Kpn showed significant differences in antimicrobial susceptibility to only 5 out of 22 antimicrobial agents (P < 0.05); the Ecl showed significant differences in susceptibility only to two antimicrobial agents, LVX and TOB (P < 0.01). Conclusion: The antimicrobial susceptibility of Enterobacteriaceae was significantly different among specimen type, age bracket and sex of patients, which is of great significance for the treatment and research of infection.