Successful Removal and Replacement of a Stuck Hemodialysis Catheter via Thoracotomy: Report of Two Cases and Literature Review.

Introduction: Stuck tunneled central venous catheters (CVCs) have been increasingly reported. In rare cases, the impossibility of extracting the CVC from the central vein after regular traction is the result of rigid adhesions to the surrounding fibrin sheath. Forced traction during catheter removal can cause serious complications, including cardiac tamponade, hemothorax, and hemorrhagic shock. Knowledge and experience on how to properly manage the stuck catheter are still limited. Case Presentation: Here, we present two cases that highlight the successful removal of the stuck tunneled CVC via thoracotomy through the close collaboration of multidisciplinary specialists in the best possible way. Both patients underwent an unsuccessful attempt at thrombolytic therapy with urokinase, catheter traction under the guidance of digital subtraction angiography and intraluminal balloon dilation. And we reviewed the literature on stuck catheters in the hope of providing knowledge and effective approaches to attempted removal of stuck catheters. Conclusion: There is no standardized procedure for dealing with stuck catheters. Intraluminal percutaneous transluminal angioplasty should be considered as the first-line treatment, while open surgery represents a second option only in the event of failure. Care must be taken that forced extubation can cause patients life-threatening.

Improving salt-tolerant artificial consortium of Bacillus amyloliquefaciens for bioconverting food waste to lipopeptides.

High-salt content in food waste (FW) affects its resource utilization during biotransformation. In this study, adaptive laboratory evolution (ALE), gene editing, and artificial consortia were performed out to improve the salt-tolerance of Bacillus amyloliquefaciens for producing lipopeptide under FW and seawater. High-salt stress significantly decreased lipopeptide production in the B. amyloliquefaciens HM618 and ALE strains. The total lipopeptide production in the recombinant B. amyloliquefaciens HM-4KSMSO after overexpressing the ion transportor gene ktrA and proline transporter gene opuE and replacing the promoter of gene mrp was 1.34 times higher than that in the strain HM618 in medium containing 30 g/L NaCl. Lipopeptide production under salt-tolerant consortia containing two strains (HM-4KSMSO and Corynebacterium glutamicum) and three-strains (HM-4KSMSO, salt-tolerant C. glutamicum, and Yarrowia lipolytica) was 1.81- and 2.28-fold higher than that under pure culture in a medium containing FW or both FW and seawater, respectively. These findings provide a new strategy for using high-salt FW and seawater to produce value-added chemicals.

Combinatorial metabolic engineering of Bacillus subtilis for de novo production of polymyxin B.

Polymyxin is a lipopeptide antibiotic that is effective against multidrug-resistant Gram-negative bacteria. However, its clinical development is limited due to low titer and the presence of homologs. To address this, the polymyxin gene cluster was integrated into Bacillus subtilis, and sfp from Paenibacillus polymyxa was expressed heterologously, enabling recombinant B. subtilis to synthesize polymyxin B. Regulating NRPS domain inhibited formation of polymyxin B2 and B3. The production of polymyxin B increased to 329.7 mg/L by replacing the native promoters of pmxA, pmxB, and pmxE with PfusA, C2up, and PfusA, respectively. Further enhancement in this production, up to 616.1 mg/L, was achieved by improving the synthesis ability of 6-methyloctanoic acid compared to the original strain expressing polymyxin heterologously. Additionally, incorporating an anikasin-derived domain into the hybrid nonribosomal peptide synthase of polymyxin increased the B1 ratio in polymyxin B from 57.5% to 62.2%. Through optimization of peptone supply in the fermentation medium and fermentation in a 5.0-L bioreactor, the final polymyxin B titer reached 962.1 mg/L, with a yield of 19.24 mg/g maltodextrin and a productivity of 10.02 mg/(L·h). This study demonstrates a successful approach for enhancing polymyxin B production and increasing the B1 ratio through combinatorial metabolic engineering.

Synthesis and biological evaluation of 4-imidazolidinone-containing compounds as potent inhibitors of the MDM2/p53 interaction.

Inhibition of MDM2/p53 interaction with small-molecule inhibitors stabilizes p53 from MDM2 mediated degradation, which is a promising strategy for the treatment of cancer. In this report, a novel series of 4-imidazolidinone-containing compounds have been synthesized and tested in MDM2/p53 and MDM4/p53 FP binding assays. Upon SAR studies, compounds 2 (TB114) and 22 were identified as the most potent inhibitors of MDM2/p53 but not MDM4/p53 interactions. Both 2 and 22 exhibited strong antiproliferative activities in HCT-116 and MOLM-13 cell lines harboring wild type p53. Mechanistic studies show that 2 and 22 dose-dependently activated p53 and its target genes and induced apoptosis in cells based on the Western blot, qPCR, and flow cytometry assays. In addition, the antiproliferative activities of 2 and 22 were dependent on wild type p53, while they were not toxic to HEK-293 kidney cells. Furthermore, the on-target activities of 2 were general and applicable to other cancer cell lines with wild type p53. These attributes make 2 a good candidate for future optimization to discover a potential treatment of wild-type p53 cancer.

Spatial and temporal differences and convergence analysis of multidimensional relative poverty in ethnic areas.

Reducing multidimensional relative poverty is one of the important issues in the current global poverty governance field. This article takes 12 ethnic regions in China as the research object and constructs a multidimensional relative poverty measurement system. The calculated multidimensional relative poverty index is decomposed according to provinces, cities, dimensions, and indicators. Then, the Dagum Gini coefficient and convergence analysis are used to analyze spatiotemporal heterogeneity and convergence characteristics. The results show that the multi-dimensional relative poverty situation of various provinces in ethnic minority areas has improved from 2012 to 2021, among which Tibet province is the most serious and Shaanxi is the best. According to the analysis of convergence, it was observed that there is no σ-convergence of multidimensional relative poverty in ethnic areas in general, and there is absolute ß-convergence in general and in the southwest and northwest regions, and there is no absolute ß-convergence in the northeast region. Based on this, policy recommendations for reducing multidimensional relative poverty are proposed at the end of the article. Compared with previous studies, this article focuses on ethnic regions that are easily overlooked. Starting from the dimensions of economy, social development, and ecological environment, the poverty measurement system has been enriched.

Challenging anticoagulation therapy for multiple primary malignant tumors combined with thrombosis: A case report and review of literature.

BACKGROUND: Venous thromboembolism significantly contributes to patient deterioration and mortality. Management of its etiology and anticoagulation treatment is intricate, necessitating a comprehensive consideration of various factors, including the bleeding risk, dosage, specific anticoagulant medications, and duration of therapy. Herein, a case of lower extremity thrombosis with multiple primary malignant tumors and high risk of bleeding was reviewed to summarize the shortcomings of treatment and prudent anticoagulation experience. CASE SUMMARY: An 83-year-old female patient was admitted to the hospital due to a 2-wk history of left lower extremity edema that had worsened over 2 d. Considering her medical history and relevant post-admission investigations, it was determined that the development of left lower extremity venous thrombosis and pulmonary embolism in this case could be attributed to a combination of factors, including multiple primary malignant tumors, iliac venous compression syndrome, previous novel coronavirus infection, and inadequate treatment for prior thrombotic events. However, the selection of appropriate anticoagulant medications, determination of optimal drug dosages, and establishment of an appropriate duration of anticoagulation therapy were important because of concurrent thrombocytopenia, decreased quantitative fibrinogen levels, and renal insufficiency. CONCLUSION: Anticoagulant prophylaxis should be promptly initiated in cases of high-risk thrombosis. Individualized anticoagulation therapy is required for complex thrombosis.

Exogenous insulin autoimmune syndrome: A case report and review of literature.

BACKGROUND: Insulin autoimmune syndrome (IAS) is a severe manifestation of spontaneous hypoglycemia. It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies (IAAs), which are induced by endogenous insulin circulating in the bloodstream. It is distinguished by recurring instances of spontaneous hypoglycemia, the presence of IAA within the body, a substantial elevation in serum insulin levels, and an absence of prior exogenous insulin administration. Nevertheless, recent studies show that both conventional insulin and its analogs can induce IAS episodes, giving rise to the notion of non-classical IAS. Therefore, more attention should be paid to these diseases. CASE SUMMARY: In this case report, we present a rare case of non-classical IAS in an 83-year-old male patient who present with symptoms of a psychiatric disorder. Upon symptom onset, the patient exhibited Whipple's triad (including hypoglycemia, blood glucose level less than 2.8 mmol/L during onset, and rapid relief of hypoglycemic symptoms after glucose administration). Concurrently, his serum insulin level was significantly elevated, which contradicted his C-peptide levels. After a comprehensive examination, the patient was diagnosed with exogenous insulin autoimmune syndrome. Considering that the patient had type 2 diabetes mellitus and a history of exogenous insulin use before disease onset, it was presumed that non classical IAS was induced by this condition. The PubMed database was used to search for previous cases of IAS and non-classical IAS to analyze their characteristics and treatment approaches. CONCLUSION: The occurrence of non-classical IAS is associated with exogenous insulin or its analogs, as well as with sulfhydryl drugs. Symptoms can be effectively alleviated through the discontinuation of relevant medications, administration of hormones or immunosuppressants, plasma exchange, and lifestyle adjustments.

Integrated Biofilm Modification and Transcriptional Analysis for Improving Fengycin Production in Bacillus amyloliquefaciens.

Although fengycin exhibits broad-spectrum antifungal properties, its application is hindered due to its low biosynthesis level and the co-existence of iturin A and surfactin in Bacillus amyloliquefaciens HM618, a probiotic strain. In this study, transcriptome analysis and gene editing were used to explore the potential mechanisms regulating fengycin production in B. amyloliquefaciens. The fengycin level of B. amyloliquefacien HM-3 (∆itu-ΔsrfAA) was 88.41 mg/L after simultaneously inhibiting the biosyntheses of iturin A and surfactin. The knockout of gene eps associated with biofilm formation significantly increased the fengycin level of the strain HM618, whereas the fengycin level decreased 32.05% after knocking out sinI, a regulator of biofilm formation. Transcriptome analysis revealed that the differentially expressed genes, involved in pathways of amino acid and fatty acid syntheses, were significantly down-regulated in the recombinant strains, which is likely associated with a decrease of fengycin production. The knockout of gene comQXPA and subsequent transcriptome analysis revealed that the ComQXPA quorum sensing system played a positive regulatory role in fengycin production. Through targeted genetic modifications and fermentation optimization, the fengycin production of the engineered strain HM-12 (∆itu-ΔsrfAA-ΔyvbJ) in a 5-L fermenter reached 1.172 g/L, a 12.26-fold increase compared to the fengycin level in the strain HM-3 (∆itu-ΔsrfAA) in the Erlenmeyer flask. Taken together, these results reveal the underlying metabolic mechanisms associated with fengycin synthesis and provide a potential strategy for improving fengycin production in B. amyloliquefaciens.

The ACE2/Ang-(1-7)/MasR axis alleviates brain injury after cardiopulmonary resuscitation in rabbits by activating PI3K/Akt signaling.

Background: Death among resuscitated patients is mainly caused by brain injury after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The angiotensin converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor (MasR) axis has beneficial effects on brain injury. Therefore, we examined the roles of the ACE2/Ang-(1-7)/MasR axis in brain injury after CA/CPR. Method: We used a total of 76 male New Zealand rabbits, among which 10 rabbits underwent sham operation and 66 rabbits received CA/CPR. Neurological functions were determined by assessing serum levels of neuron-specific enolase and S100 calcium-binding protein B and neurological deficit scores. Brain water content was estimated. Neuronal apoptosis in the hippocampus was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assays. The expression levels of various genes were measured by enzyme-linked immunosorbent assay and western blotting. Results: Ang-(1-7) (MasR activator) alleviated CA/CPR-induced neurological deficits, brain edema, and neuronal damage, and A779 (MasR antagonist) had the opposite functions. The stimulation of ACE2/Ang-(1-7)/MasR inactivated the ACE/Ang II/AT1R axis and activated PI3K/Akt signaling. Inhibiting PI3K/Akt signaling inhibited Ang-(1-7)-mediated protection against brain damage after CA/CPR. Conclusion: Collectively, the ACE2/Ang-(1-7)/MasR axis alleviates CA/CPR-induced brain injury through attenuating hippocampal neuronal apoptosis by activating PI3K/Akt signaling.

Establishing and Validating an Innovative Focal Adhesion-Linked Gene Signature for Enhanced Prognostic Assessment in Endometrial Cancer.

Studies have highlighted the significant role of focal adhesion signaling in cancer. Nevertheless, its specific involvement in the pathogenesis of endometrial cancer and its clinical significance remains uncertain. We analyzed TCGA-UCEC and GSE119041 datasets with corresponding clinical data to investigate focal adhesion-related gene expression and their clinical significance. A signature, "FA-riskScore," was developed using LASSO regression in the TCGA cohort and validated in the GSE dataset. The FA-riskScore was compared with four existing models in terms of their prediction performance. We employed univariate and multivariate Cox regression analyses towards FA-riskScore to assess its independent prognostic value. A prognostic evaluation nomogram based on our model and clinical indexes was established subsequently. Biological and immune differences between high- and low-risk groups were explored through functional enrichment, PPI network analysis, mutation mining, TME evaluation, and single-cell analysis. Sensitivity tests on commonly targeted drugs were performed on both groups, and Connectivity MAP identified potentially effective molecules for high-risk patients. qRT-PCR validated the expressions of FA-riskScore genes. FA-riskScore, based on FN1, RELN, PARVG, and PTEN, indicated a poorer prognosis for high-risk patients. Compared with published models, FA-riskScore achieved better and more stable performance. High-risk groups exhibited a more challenging TME and suppressive immune status. qRT-PCR showed differential expression in FN1, RELN, and PTEN. Connectivity MAP analysis suggested that BU-239, potassium-canrenoate, and tubocurarine are effective for high-risk patients. This study introduces a novel prognostic model for endometrial cancer and offers insights into focal adhesion's role in cancer pathogenesis.

High-Density Polyethylene Custom Focusing Lenses for High-Resolution Transient Terahertz Biomedical Imaging Sensors.

Transient terahertz time-domain spectroscopy (THz-TDS) imaging has emerged as a novel non-ionizing and noninvasive biomedical imaging modality, designed for the detection and characterization of a variety of tissue malignancies due to their high signal-to-noise ratio and submillimeter resolution. We report our design of a pair of aspheric focusing lenses using a commercially available lens-design software that resulted in about 200 × 200-µm2 focal spot size corresponding to the 1-THz frequency. The lenses are made of high-density polyethylene (HDPE) obtained using a lathe fabrication and are integrated into a THz-TDS system that includes low-temperature GaAs photoconductive antennae as both a THz emitter and detector. The system is used to generate high-resolution, two-dimensional (2D) images of formalin-fixed, paraffin-embedded murine pancreas tissue blocks. The performance of these focusing lenses is compared to the older system based on a pair of short-focal-length, hemispherical polytetrafluoroethylene (TeflonTM) lenses and is characterized using THz-domain measurements, resulting in 2D maps of the tissue refractive index and absorption coefficient as imaging markers. For a quantitative evaluation of the lens effect on the image resolution, we formulated a lateral resolution parameter, R2080, defined as the distance required for a 20-80% transition of the imaging marker from the bare paraffin region to the tissue region in the same image frame. The R2080 parameter clearly demonstrates the advantage of the HDPE lenses over TeflonTM lenses. The lens-design approach presented here can be successfully implemented in other THz-TDS setups with known THz emitter and detector specifications.

Breaking barriers in cancer treatment: nanobiohybrids empowered by modified bacteria and vesicles.

Cancer, the leading global cause of mortality, poses a formidable challenge for treatment. The effectiveness of cancer therapies, ranging from chemotherapy to immunotherapy, relies on the precise delivery of therapeutic agents to tumor tissues. Nanobiohybrids, resulting from the fusion of bacteria with nanomaterials, constitute a promising delivery system. Nanobiohybrids offer several advantages, including the ability to target tumors, genetic engineering capabilities, programmed product creation, and the potential for multimodal treatment. Recent advances in targeted tumor treatments have leveraged bacteria-based nanobiohybrids. Here, we outline the progress in cancer treatment using nanobiohybrids. Our focus is particularly on various therapeutic approaches within the context of nanobiohybrid systems, where bacteria are integrated with nanomaterials to combat cancer. It has been demonstrated that bacteria-based nanobiohybrids present a robust and effective method for tumor theranostics.

DPP: deep phase prior for parallel imaging with wave encoding.

OBJECTIVE: In MR parallel imaging with virtual channel-expanded Wave encoding, limitations are imposed on the ability to comprehensively and accurately characterize the background phase. These limitations are primarily attributed to the calibration process relying solely on center low-frequency ACS data for calibration. Approach: To tackle the challenge of accurately estimating the background phase in wave encoding, a novel deep neural network model guided by deep phase priors (DPP) is proposed with integrated virtual conjugate coil (VCC) extension. Concretely, within the proposed framework, the background phase is implicitly characterized by employing a carefully designed decoder convolutional neural network, leveraging the inherent characteristics of phase smoothness and compact support in the transformed domain. Furthermore, the proposed model with wave encoding benefits from additional priors, which incorporate transmission sparsity of the latent image and coil sensitivity smoothness. Main results: Ablation experiments were conducted to ascertain the proposed method's capability to implicitly represent CSM and the background phase. Subsequently, the superiority of the proposed method is demonstrated through confidence comparisons with competing methods, employing 4-fold and 5-fold acceleration experiments. In achieving 4-fold and 5-fold acceleration, the optimal quantitative metrics (PSNR/SSIM/NMSE) are 44.1359 dB/0.9863/0.0008 (4-fold) and 41.2074/0.9846/0.0017 (5-fold), respectively. Furthermore, the generalizability of the proposed method is further validated by conducting acceleration experiments with T1, T2, T2*, and various undersampling patterns. In addition, the DPP delivered much better performance than the conventional methods by exploring accelerated phase-sensitive SWI imaging. In SWI accelerated imaging, it also surpasses the optimal competing method in terms of (PSNR/SSIM/NMSE) with 0.096%/0.009%/0.0017%. Significance: The proposed method enables precise characterization of the background phase in the integrated VCC and wave encoding framework, supported via theoretical analysis and empirical findings. Our code is available at: https://github.com/sober235/DPP.

Two-Dimensional Os2Se3 Nanosheet: A Ferroelectric Metal with Room-Temperature Ferromagnetism.

Two-dimensional (2D) ferroelectric metals (FEMs) possess intriguing characteristics, such as unconventional superconductivity and the nonlinear anomalous Hall effect. However, their occurrence is exceedingly rare due to mutual repulsion between ferroelectricity and metallicity. In addition, further incorporating other features like ferromagnetism into FEMs to enhance their functionalities poses a significantly greater challenge. Here, via first-principles calculations, we demonstrate a case of an FEM that features a coexistence of room-temperature ferromagnetism, ferroelectricity, and metallicity in a thermodynamically stable 2D Os2Se3. It presents a vertical electric polarization of 3.00 pC/m that exceeds those of most FEMs and a moderate polarization switching barrier of 0.22 eV per formula unit. Moreover, 2D Os2Se3 exhibits robust ferromagnetism (Curie temperature TC ≈ 527 K) and a sizable magnetic anisotropy energy (-30.87 meV per formula unit). Furthermore, highly magnetization-dependent electrical conductivity is revealed, indicative of strong magnetoelectric coupling. Berry curvature calculation suggests that the FEM might exhibit nontrivial band topology.

Correlation Analysis of NAMPT rs61330082 Polymorphism in Type 2 Diabetes Mellitus Combined with Hypertension.

Introduction: This study aimed to investigate the association of Nicotinamide phosphoribosyl transferase (NAMPT) rs61330082 polymorphism with co-morbid hypertension (HTN) and the progression of hypertension in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: A total of 453 T2DM patients were genotyped for the polymorphism of rs61330082 using SNP-scan high-throughput technology. These patients were divided into T2DM group (261 patients) and T2DM combined with hypertension group (T2MH, 192 patients). The T2MH group was further categorized into Grade I, Grade II, and Grade III based on the results of the Hypertension Grade Score. Peripheral blood plasma urea, plasma creatinine, renin-angiotensin system (RAS) indexes, and lipid biochemistry indexes were measured in patients and analyzed in relation to NAMTP polymorphisms. Results: We found that the presence of the NAMPT rs61330082-AA genotype was associated with a significantly increased risk of developing higher-grade hypertension in patients with T2MH. In addition, the A allele of the NAMPT rs61330082 gene displayed more associated in developing a higher grade of hypertension compared to the G allele. Also, the level of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) increased with hypertension grade in the NAMPT rs61330082-GG genotype. Conclusion: NAMPT rs61330082 polymorphism was significantly associated with the progression of hypertension grade in T2MH patients and also affected plasma creatinine and LDL-c levels.

Regional Inequality and Associated Factors of Emergency Medicine Beds Distribution in China.

Objective: The regional inequality of emergency medicine beds distribution has a great impact on population health as well as the accessibility of emergency services. This study aimed to explore the regional inequality of emergency medicine bed distribution and its influencing factors. Methods: The Gini coefficient and health resource agglomeration were used to analyze the regional inequality of emergency medicine beds distribution by area from 2012 to 2021 in China. Grey correlation models were used to explore the factors influencing the regional inequality of emergency medicine beds distribution. Results: From 2012 to 2021, Gini coefficients of emergency medicine beds distribution by geographic in China showed a worsening trend, rising from 0.6229 to 0.6636. The average HRAD index was 3.43 in the east and 0.44 in the west. Population structure factors have the greatest influence on the regional inequality of emergency medicine beds distribution. Conclusion: Health resources allocation strategy only according to population size should be changed. In formulating policies for emergency medicine beds allocation should take into account population structure, financial structure of expenditure, the inequality of geographical distribution and so on.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

China's carbon-neutral policies will reduce short-term PM2.5-associated excess incidence of cardiovascular diseases.

China's carbon-neutral target could have benefits for ambient fine particulate matter (PM2.5)-associated mortality. Although previous studies have researched such benefits, the potential impact on cardiovascular disease incidence burden is yet to be investigated thoroughly. Here, we first estimate the association between short-term PM2.5 exposure and the incidence of stroke and coronary heart disease (CHD) via a case-crossover study before projecting future changes in short-term PM2.5-associated excess incidence across China from 2025 to 2060 under three different emission scenarios. We find that, compared to the 2015-2020 baseline, average PM2.5 concentrations nationwide in 2060 under SSP119 (an approximation of a carbon-neutral scenario) are projected to decrease by 81.07%. The short-term PM2.5-related excess incidence of stroke and CHD is projected to be reduced to 3,352 cases (95% confidence interval: 939, 5,738)-compared with 34,485 cases under a medium-emissions scenario (SSP245)-and is expected to be accompanied by a 95% reduction in the related economic burden. China's carbon-neutral policies are likely to bring health benefits for cardiovascular disease by reducing short-term PM2.5-related incidence burden.