Influencing Factors of Delirium during Recovery in Urological Postoperative Patients Undergoing Sevoflurane Anaesthesia.

OBJECTIVE: To analyse the incidence and influencing factors of delirium during recovery in urological postoperative patients undergoing sevoflurane anaesthesia. METHODS: The clinical data of patients undergoing sevoflurane anaesthesia in the urology surgery department in our hospital from January 2022 to December 2022 were retrospectively analysed. The incidence of delirium during the recovery period was recorded by using the Chinese version of the Confusion Assessment Method (CAM) for Severity of Delirium after surgery, and the patients were divided into occurrence and non-occurrence groups. Whether delirium occurred during recovery was determined through univariate analysis. In binary logistic regression analysis, the occurrence of emergence delirium was the dependent variable, and the variables with statistical differences in the univariate analysis were the independent variables. The influencing factors of emergence delirium in post-urological surgery patients who underwent sevoflurane anaesthesia were determined. RESULTS: Delirium during recovery occurred in 10 of 100 patients (10.00%). Odds ratio (OR) of age (OR = 1.445, p = 0.022), history of diabetes (OR = 1.798, p = 0.010), operation time (OR = 1.670, p = 0.008), American Society of Anesthesiologists (ASA) classification (OR = 1.740, p = 0.006) and sevoflurane inhalation concentration (OR = 1.890, p = 0.001) are the influencing factors of postoperative delirium in urologic patients undergoing sevoflurane anaesthesia. CONCLUSIONS: Age, history of diabetes, operation time, ASA classification and sevoflurane inhalation concentration are the influencing factors.

Constituents of Chimaphila japonica and Their Diuretic Activity.

Three new phenols (1-3), one new cyclohexanol (4), two known phenols (5-6), and six known flavonoids (7-12) were isolated from the n-butanol of the 75% ethanol extract of all plants of Chimaphila japonica Miq. Among them, compound 5 was named and described in its entirety for the first time, and compounds 9 and 10 were reported in C. japonica for the first time. The structures of all compounds were confirmed using a comprehensive analysis of 1D and 2D NMR and HRESIMS data. Biological results show that compounds 4, 7, and 11 exhibited potent diuretic activity. The modes of interaction between the selected compounds and the target diuretic-related WNK1 kinase were investigated in a preliminary molecular docking study. These results provided insight into the chemodiversity and potential diuretic activities of metabolites in C. japonica.

Influencing Factors of Delirium during Recovery in Urological Postoperative Patients Undergoing Sevoflurane Anaesthesia

Objective: To analyse the incidence and influencing factors of delirium during recovery in urological postoperative patients undergoing sevoflurane anaesthesia. Methods: The clinical data of patients undergoing sevoflurane anaesthesia in the urology surgery department in our hospital from January 2022 to December 2022 were retrospectively analysed. The incidence of delirium during the recovery period was recorded by using the Chinese version of the Confusion Assessment Method (CAM) for Severity of Delirium after surgery, and the patients were divided into occurrence and non-occurrence groups. Whether delirium occurred during recovery was determined through univariate analysis. In binary logistic regression analysis, the occurrence of emergence delirium was the dependent variable, and the variables with statistical differences in the univariate analysis were the independent variables. The influencing factors of emergence delirium in post-urological surgery patients who underwent sevoflurane anaesthesia were determined. Results: Delirium during recovery occurred in 10 of 100 patients (10.00%). Odds ratio (OR) of age (OR = 1.445, p = 0.022), history of diabetes (OR = 1.798, p = 0.010), operation time (OR = 1.670, p = 0.008), American Society of Anesthesiologists (ASA) classification (OR = 1.740, p = 0.006) and sevoflurane inhalation concentration (OR = 1.890, p = 0.001) are the influencing factors of postoperative delirium in urologic patients undergoing sevoflurane anaesthesia. Conclusions: Age, history of diabetes, operation time, ASA classification and sevoflurane inhalation concentration are the influencing factors. (AU)

Emerging role of RNA modification and long noncoding RNA interaction in cancer.

RNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence and progression of cancer through multiple pathways. The function and expression of these epigenetic regulators have gradually become a hot topic in cancer research. Mutation and regulation of noncoding RNA, especially lncRNA, play a major role in cancer. Generally, lncRNAs exert tumor-suppressive or oncogenic functions and its dysregulation can promote tumor occurrence and metastasis. In this review, we summarize N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine modifications in lncRNAs. Furthermore, we discuss the relationship between epigenetic RNA modification and lncRNA interaction and cancer progression in various cancers. Therefore, this review gives a comprehensive understanding of the mechanisms by which RNA modification affects the progression of various cancers by regulating lncRNAs, which may shed new light on cancer research and provide new insights into cancer therapy.

GDF11 mitigates high glucose-induced cardiomyocytes apoptosis by inhibiting the ALKBH5-FOXO3-CDR1as/Hippo signaling pathway.

Diabetic cardiomyopathy remains a formidable health challenge with a high mortality rate and no targeted treatments. Growth differentiation factor 11 (GDF11) has shown promising effects on cardiovascular diseases; however, its role and the underlying mechanism in regulating diabetic cardiomyopathy remain unclear. In this study, we developed mouse models of diabetic cardiomyopathy using leptin receptor-deficient (db/db) mice and streptozocin-induced C57BL/6 mice. The diabetic cardiomyopathy model mice exhibited apparent structural damage in cardiac tissues and a significant increase in the expression of apoptosis-related proteins. Notably, we observed a significant decreased expression of GDF11 in the myocardium of mice with diabetic cardiomyopathy. Moreover, GDF11 cardiac-specific knock-in mice (transgenic mice) exhibited improved cardiac function and reduced apoptosis. Moreover, exogenous administration of GDF11 mitigated high glucose-induced cardiomyocyte apoptosis. Mechanistically, we demonstrated that GDF11 alleviated high glucose-induced cardiomyocytes apoptosis by inhibiting the activation of the alkylation repair homolog 5 (ALKBH5)-forkhead box group O3a (FOXO3)-cerebellar degeneration-related protein 1 transcript (CDR1as)/Hippo signaling pathway. Consequently, this novel mechanism effectively counteracted myocardial cell apoptosis, providing valuable insights into potential therapeutic strategies for clinical diabetic cardiomyopathy.

Systematic evaluation of the impact of standard storage conditions on plasmid conjugation behavior in wastewater samples.

Filter mating experiment is widely used to study the conjugation behavior of plasmids and associated antibiotic resistance in environmental settings, however, the influence and biases brought by sample storage conditions (temperature and duration) were not yet systematically elaborated. This study systematically investigated the influence of standard storage conditions (4 °C, -20 °C, -80 °C) on plasmid conjugation behavior in influent (Inf) and activated sludge (AS) samples from sewage treatment plants (STP). The findings revealed a significant reduction in conjugation efficiency under all the tested storage conditions except for 1-week storage at 4 °C. Notably, storing at -80 °C maintained conjugation activities in activated sludge more effectively compared to -20 °C. However, the preservation performance was less effective for influent samples, which consist mainly of anaerobe-dominant communities. Systematic loss of IncH-type plasmids was observed in influent samples stored at 4 °C and -20 °C. Correspondingly, the plasmid-carrying resistome genotypes detected in the influent samples showed a clear downward trend with the increase in storage duration when stored at 4 °C and -20 °C. A relatively uniform composition in terms of incompatibility type and resistome profile was observed across activated sludge samples, regardless of the varied storage conditions. This study highlights the critical impact of storage conditions on plasmid conjugation behavior and resistome composition, offering valuable insights for optimal sample handling in resistome research.

Dysregulation of immunity by cigarette smoking promotes inflammation and cancer: A review.

Smoking is a serious global health issue. Cigarette smoking contains over 7000 different chemicals. The main harmful components include nicotine, acrolein, aromatic hydrocarbons and heavy metals, which play the key role for cigarette-induced inflammation and carcinogenesis. Growing evidences show that cigarette smoking and its components exert a remarkable impact on regulation of immunity and dysregulated immunity promotes inflammation and cancer. Therefore, this comprehensive and up-to-date review covers four interrelated topics, including cigarette smoking, inflammation, cancer and immune system. The known harmful chemicals from cigarette smoking were summarized. Importantly, we discussed in depth the impact of cigarette smoking on the formation of inflammatory or tumor microenvironment, primarily by affecting immune effector cells, such as macrophages, neutrophils, and T lymphocytes. Furthermore, the main molecular mechanisms by which cigarette smoking induces inflammation and cancer, including changes in epigenetics, DNA damage and others were further summarized. This article will contribute to a better understanding of the impact of cigarette smoking on inducing inflammation and cancer.

LncRNA RP11-93B14.5 promotes gastric cancer cell growth through PI3K/AKT signaling pathway.

OBJECTIVE: Emerging evidence indicates that long non-coding RNA (lncRNA) RP11-93B14.5 facilitates tumor progression in variety of malignancies. The present study proposed to study the functional effect of lncRNA RP11-93B14.5 in gastric cancer (GC) as well as the underlying mechanism. METHODS: Bioinformatics analysis was utilized to analyze lncRNA expression in GC tissues. siRNA was used for knockdown of RP11-93B14.5 in GC cells MKN45 and KATO III. The stable knockdown cell lines were constructed by CRISPR-Cas9. Cell counting kit-8 (CCK-8) assay and soft agar colony formation assay were used to analyze GC cell viability. Flow cytometry analysis was performed to analyze the cell cycle distribution of MKN45 and KATO III. RNA sequencing (RNA-seq) was employed to detect differential genes after transfection with siRP11-93B14.5. Quantitative PCR (Q-PCR) was used to examine gene expression in GC cell lines. Western-blot assay was used to measure protein levels. RNA fluorescent in situ hybridization (FISH) was conducted for lncRNA cellular location and expression. RESULTS: Based on the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database, RP11-93B14.5 was upregulated in GC tissue, which was also verified in GC cell lines in comparison to the normal gastric epithelial HFE145 cells. Knockdown of RP11-93B14.5 decreased cell viability and the colony number of MKN45 and KATO III cells, and altered cell cycle distribution in vitro. RNA-seq analysis revealed RP11-93B14.5 may modulate genes expression of S100A2 and TIMP2 in MKN45 and KATO III cells. Mechanistically, RP11-93B14.5 may drive the progression of GC via S100A2 related-PI3K/AKT signaling pathway. CONCLUSIONS: LncRNA RP11-93B14.5 knockdown alleviated the malignant phenotypes of GC cells through regulating PI3K/AKT. Our results provide evidence for the role of lncRNAs in regulating tumor progression.

Elevated Expression of Two Pore Potassium Channel THIK-1 in Alzheimer's Disease: An Inflammatory Mechanism.

INTRODUCTION: Tandem pore domain halothane-inhibited K+ channel 1 (THIK-1, coded by KCNK13) provides an upstream regulation of the activation of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which has been suggested as one of the key mechanisms of the pathological process in neurodegeneration mainly from in vitro and in vivo model systems studies. However, unequivocal evidence from neurodegenerative disorders has been lacking. OBJECTIVE: To investigate the involvement of the THIK-1/NLRP3 pathway in the pathological process of Alzheimer's disease (AD) and Parkinson's disease (PD). METHODS: This study investigated gene expression of markers in the THIK-1/NLRP3 pathway in an animal model representing AD as well as in human postmortem brains of AD and PD by quantitative real-time PCR. THIK-1 protein expression was determined using automated capillary electrophoresis immunoblotting. Furthermore, DNA methylation of KCNK13 was analysed in AD cohort by pyrosequencing. RESULTS: A substantial upregulation of KCNK13, glial activation markers, NLRP3 inflammasome components, and IL1B was observed in the animal study. Increased expression of KCNK13 support an inflammatory glial cell activation in both advanced AD and PD. The increase in KCNK13 expression was also supported by downregulation in DNA methylation of KCNK13 in AD. CONCLUSIONS: The association between THIK-1 K+ channels expression and pathology changes indicates a THIK-1-induced activation of this glial subtype in AD and PD. Therefore, specific blocks of the microglial THIK-1 K+ channels at the early stage of AD and PD may be beneficial for the patients.

Chemical profiling and investigation of molecular mechanisms underlying anti-hepatocellular carcinoma activity of extracts from Polygonum perfoliatum L.

Polygonum perfoliatum L. is an herbal medicine that has been extensively used in traditional Chinese medicine to treat various health conditions ranging from ancient internal to surgical and gynecological diseases. Numerous studies suggest that P. perfoliatum extract elicits significant anti-tumor, anti-inflammatory, anti-bacterial, and anti-viral effects. Nevertheless, the underlying mechanisms of its anti-liver cancer effects remain poorly understood. Our study suggests that P. perfoliatum stem extract (PPLA) has a favorable safety profile and exhibits a significant anti-liver cancer effect both in vitro and in vivo. We identified that PPLA activates the cGMP-PKG signaling pathway, and key regulatory genes including ADRA1B, PLCB2, PRKG2, CALML4, and GLO1 involved in this activation. Moreover, PPLA modulates the expression of genes responsible for the cell cycle. Additionally, we identified four constituents of PPLA, namely taxifolin, myricetin, eriodictyol, and pinocembrin, that plausibly act via the cGMP-PKG signaling pathway. Both in vitro and in vivo experiments confirmed that PPLA, along with its constituting compounds taxifolin, myricetin, and eriodictyol, exhibit potent anti-cancer activities and hold the promise of being developed into therapeutic agents.

Optimised Agrobacterium-Mediated Transformation and Application of Developmental Regulators Improve Regeneration Efficiency in Melons.

Melon (Cucumis melo L.) is a protected crop in China with high economic value. Agrobacterium-mediated genetic transformation is a powerful tool to improve agronomic traits and obtain elite germplasm. However, current transformation protocols in melons are inefficient and highly genotype-dependent. To improve transformation in melon, we tested different infiltration methods for Agrobacterium-mediated transformation. Among these methods, micro-brushing and sonication for 20 s, followed by vacuum infiltration at -1.0 kPa for 90 s, resulted in the strongest green fluorescent protein signal and increased the proportion of infected explants. We transformed melon with developmental regulatory genes AtGRF5, AtPLT5, AtBBM, AtWUS, AtWOX5, and AtWIND1 from Arabidopsis and estimated regeneration frequencies as the number of regenerating shoots/total number of inoculated explants in the selection medium. The overexpression of AtGRF5 and AtPLT5 in melon resulted in transformation efficiencies of 42.3% and 33% in ZHF and 45.6% and 32.9% in Z12, respectively, which were significantly higher than those of the control. AtGRF5 and AtPLT5 expression cassettes were added to CRISPR/Cas9 genome-editing vectors to obtain transgenic phytoene desaturase CmPDS knockout mutants. Using AtGRF5 or AtPLT5, multi-allelic mutations were observed at CmPDS target sites in recalcitrant melon genotypes. This strategy enables genotype-flexible transformation and promotes precise genome modification technologies in melons.

Does each Component of Reactive Oxygen Species have a Dual Role in the Tumor Microenvironment?

Reactive oxygen species (ROS) are a class of highly reactive oxidizing molecules, including superoxide anion (O2•-) and hydrogen peroxide (H2O2), among others. Moderate levels of ROS play a crucial role in regulating cellular signaling and maintaining cellular functions. However, abnormal ROS levels or persistent oxidative stress can lead to changes in the tumor microenvironment (TME) that favor cancer development. This review provides an overview of ROS generation, structure, and properties, as well as their effects on various components of the TME. Contrary to previous studies, our findings reveal a dual effect of ROS on different components of the TME, whereby ROS can either enhance or inhibit certain factors, ultimately leading to the promotion or suppression of the TME. For example, H2O2 has dual effects on immune cells and non-cellular components within the TME, while O2•- has dual effects on T cells and fibroblasts. Furthermore, each component demonstrates distinct mechanisms of action and ranges of influence. In the final section of the article, we summarize the current clinical applications of ROS in cancer treatment and identify certain limitations associated with existing therapeutic approaches. Therefore, this review aims to provide a comprehensive understanding of ROS, highlighting their dual effects on different components of the TME, and exploring the potential clinical applications that may pave the way for future treatment and prevention strategies.

Transfer learning based cascaded deep learning network and mask recognition for COVID-19.

The COVID-19 is still spreading today, and it has caused great harm to human beings. The system at the entrance of public places such as shopping malls and stations should check whether pedestrians are wearing masks. However, pedestrians often pass the system inspection by wearing cotton masks, scarves, etc. Therefore, the detection system not only needs to check whether pedestrians are wearing masks, but also needs to detect the type of masks. Based on the lightweight network architecture MobilenetV3, this paper proposes a cascaded deep learning network based on transfer learning, and then designs a mask recognition system based on the cascaded deep learning network. By modifying the activation function of the MobilenetV3 output layer and the structure of the model, two MobilenetV3 networks suitable for cascading are obtained. By introducing transfer learning into the training process of two modified MobilenetV3 networks and a multi-task convolutional neural network, the ImagNet underlying parameters of the network models are obtained in advance, which reduces the computational load of the models. The cascaded deep learning network consists of a multi-task convolutional neural network cascaded with these two modified MobilenetV3 networks. A multi-task convolutional neural network is used to detect faces in images, and two modified MobilenetV3 networks are used as the backbone network to extract the features of masks. After comparing with the classification results of the modified MobilenetV3 neural network before cascading, the classification accuracy of the cascading learning network is improved by 7%, and the excellent performance of the cascading network can be seen.

Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway.

Melanoma is a common skin tumor that causes a high rate of mortality, especially in Europe, North America and Oceania. Immunosuppressants such as anti-PD-1 have been used in the treatment of malignant melanoma, however, nearly 60% of patients do not respond to these treatments. Sema4D, also called CD100, is expressed in T cells and tumor tissues. Sema4D and its receptor, Plexin-B1, play crucial roles in the process of immune regulation, angiogenesis, and tumor progression. The role of Sema4D in melanoma with anti-PD-1 resistance is poorly understood. Through a combination of molecular biology techniques and in silico analysis, the role of Sema4D in improving anti-PD-L1 sensitivity in melanoma was explored. The results showed that the expression of Sema4D, Plexin-B1 and PD-L1 was significantly increased in B16-F10R cells. Sema4D knockdown synergizes with anti-PD-1 treatment, cell viability, cell invasion and migration were significantly decreased, while the apoptosis was increased, the growth of tumors on the mice was also inhibited. Mechanistically, bioinformatics analysis revealed that Sema4D is involved in the PI3K/AKT signaling pathway; the downregulation of p-PI3K/PI3K and p-AKT/AKT expression were observed in Sema4D knockdown, therefore, nivolumab resistance is related to Sema4D and Sema4D silencing can improve sensitivity to nivolumab via inhibition of the PI3K/AKT signaling pathway.

Genome enrichment of rare and unknown species from complicated microbiomes by nanopore selective sequencing.

Rare species are vital members of a microbial community, but retrieving their genomes is difficult because of their low abundance. The ReadUntil (RU) approach allows nanopore devices to sequence specific DNA molecules selectively in real time, which provides an opportunity for enriching rare species. Despite the robustness of enriching rare species by reducing the sequencing depth of known host sequences, such as the human genome, there is still a gap in RU-based enriching of rare species in environmental samples whose community composition is unclear, and many rare species have poor or incomplete reference genomes in public databases. Therefore, here we present metaRUpore to overcome this challenge. When we applied metaRUpore to a thermophilic anaerobic digester (TAD) community and human gut microbial community, it reduced coverage of the high-abundance populations and modestly increased (∼2×) the genome coverage of the rare taxa, facilitating successful recovery of near-finished metagenome-assembled genomes (nf-MAGs) of rare species. The simplicity and robustness of the approach make it accessible for laboratories with moderate computational resources, and hold the potential to become the standard practice in future metagenomic sequencing of complicated microbiomes.

Peripheral CD8+CD28+ T lymphocytes predict the efficacy and safety of PD-1/PD-L1 inhibitors in cancer patients.

Background: Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors works by reactivating immune cells. Considering the accessibility of noninvasive liquid biopsies, it is advisable to employ peripheral blood lymphocyte subsets to predict immunotherapy outcomes. Methods: We retrospectively enrolled 87 patients with available baseline circulating lymphocyte subset data who received first-line PD-1/PD-L1 inhibitors at Peking Union Medical College Hospital between May 2018 and April 2022. Immune cell counts were determined by flow cytometry. Results: Patients who responded to PD-1/PD-L1 inhibitors had significantly higher circulating CD8+CD28+ T-cell counts (median [range] count: 236 [30-536] versus 138 [36-460]/µL, p < 0.001). Using 190/µL as the cutoff value, the sensitivity and specificity of CD8+CD28+ T cells for predicting immunotherapy response were 0.689 and 0.714, respectively. Furthermore, the median progression-free survival (PFS, not reached versus 8.7 months, p < 0.001) and overall survival (OS, not reached versus 16.2 months, p < 0.001) were significantly longer in the patients with higher CD8+CD28+ T-cell counts. However, the CD8+CD28+ T-cell level was also associated with the incidence of grade 3-4 immune-related adverse events (irAEs). The sensitivity and specificity of CD8+CD28+ T cells for predicting irAEs of grade 3-4 were 0.846 and 0.667, respectively, at the threshold of CD8+CD28+ T cells ≥ 309/µL. Conclusions: High circulating CD8+CD28+ T-cell levels is a potential biomarker for immunotherapy response and better prognosis, while excessive CD8+CD28+ T cells (≥ 309/µL) may also indicate the emergence of severe irAEs.

Starch from Pueraria lobata and the amylose fraction alleviates dextran sodium sulfate induced colitis in mice.

Starch from Pueraria lobata (PLS) had polyhedral or spherical granules, displaying a bimodal size distribution within 0.6-30 µm. It showed a trimodal distribution of different molecular weight peaks, with amylose fraction of 18.2 %. PLS had a high crystallinity degree of 37.76 % and consisted of C-type starch, which gelatinized at 64.46-79.61 °C, with a high range of gelatinization (15.15 °C) and high enthalpy (13.98 J/g). A 21-day supplementation of PLS presented a regulative effect on gut microbiota in normal mice, and alleviated DSS-induced murine colitis through attenuating colonic inflammation, maintaining barrier function, preventing gut dysbiosis, increasing the short-chain fatty acids production and inhibiting NF-κB/IL-1ß axis. The protective effect of PLS against colitis was in a gut microbiota-dependent manner. Notably, the amylose fraction was responsible for the prebiotic effect of PLS. The results would potentiate new application of PLS and the amylose fraction as functional prebiotics for prevention of colitis.

Early detection of radiation-induced myocardial damage by [18F]AlF-NOTA-FAPI-04 PET/CT imaging.

PURPOSE: Retrospective analysis revealed increased [18F]AlF-NOTA-FAPI-04 uptake in the myocardium of patients with esophageal squamous cell cancer (ESCC) treated with concurrent chemoradiotherapy (CCRT). This study investigated and verified the feasibility of [18F]AlF-NOTA-FAPI-04 PET/CT for detecting radiation-induced myocardial damage (RIMD). METHODS: Myocardial FAPI uptake was analyzed before and during radiotherapy in thirteen ESCC patients treated with CCRT. In the animal study, a single dose of 50 Gy was delivered to the cardiac apex of Wistar rats (24 rats, including 16 RIMD model rats and 8 control model rats). RIMD model rats were scanned with [18F]AlF-NOTA-FAPI-04 PET/CT weekly for 12 weeks, and left ventricular ejection fraction (LVEF) was measured by magnetic resonance imaging. Dynamic, blocking, and [18F]FDG PET/CT studies (4 rats/group) were performed on RIMD rats at 5 weeks post-radiation, and histopathological analyses were conducted. RESULTS: Increased FAPI uptake in the myocardium was found after CCRT (1.53 ± 0.53 vs 1.88 ± 0.70, P = 0.015). In RIMD rats, significantly increased FAPI uptake in the damaged myocardium was observed from the 2nd week post-radiation exposure and peaked in the 5th week. Significantly more intense tracer accumulation was observed in the damaged myocardium than in the remote myocardium, as identified by decreased [18F]FDG uptake and confirmed by autoradiography, hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. The LVEF remained unchanged at the 3rd week post-radiation exposure but was remarkably decreased compared with that in the control group at the 8th week. CONCLUSION: Through clinical phenomena and animal experimental studies, this study indicated that [18F]AlF-NOTA-FAPI-04 PET/CT imaging can detect RIMD noninvasively and before a decrease in LVEF, indicating the clinical potential of [18F]AlF-NOTA-FAPI-04 as a PET/CT tracer for early monitoring of RIMD.

Targeting hypoxia-inducible factors for breast cancer therapy: A narrative review.

Hypoxia-inducible factors (HIFs), central regulators for cells to adapt to low cellular oxygen levels, are often overexpressed and activated in breast cancer. HIFs modulate the primary transcriptional response of downstream pathways and target genes in response to hypoxia, including glycolysis, angiogenesis and metastasis. They can promote the development of breast cancer and are associated with poor prognosis of breast cancer patients by regulating cancer processes closely related to tumor invasion, metastasis and drug resistance. Thus, specific targeting of HIFs may improve the efficiency of cancer therapy. In this review, we summarize the advances in HIF-related molecular mechanisms and clinical and preclinical studies of drugs targeting HIFs in breast cancer. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for HIF targeting are increasingly being developed. Therefore, we highlight the HIF related DDS, including liposomes, polymers, metal-based or carbon-based nanoparticles.

Nanopore-based long-read metagenomics uncover the resistome intrusion by antibiotic resistant bacteria from treated wastewater in receiving water body.

Wastewater treatment plant (WWTP) effluent discharge could induce the resistome enrichment in the receiving water environments. However, because of the general lack of a robust antibiotic-resistant bacteria (ARB) identification method, the driving mechanism for resistome accumulation in receiving environment is unclear. Here, we took advantage of the enhanced ARBs recognition by nanopore long reads to distinguish the indigenous ARBs and the accumulation of WWTP-borne ARBs in the receiving water body of a domestic WWTP. A bioinformatic framework (named ARGpore2: https://github.com/sustc-xylab/ARGpore2) was constructed and evaluate to facilitate antibiotic resistance genes (ARGs) and ARBs identification in nanopore reads. ARGs identification by ARGpore2 showed comparable precision and recall to that of the commonly adopt BLASTP-based method, whereas the spectrum of ARBs doubled that of the assembled Illumina dataset. Totally, we identified 33 ARBs genera carrying 65 ARG subtypes in the receiving seawater, whose concentration was in general 10 times higher than clean seawater's. Notably we report a primary resistome intrusion caused by the revival of residual microbes survived from disinfection treatment. These WWTP-borne ARBs, including several animal/human enteric pathogens, contributed up to 85% of the receiving water resistome. Plasmids and class 1 integrons were reckoned as major vehicles facilitating the persistence and dissemination of ARGs. Moreover, our work demonstrated the importance of extensive carrier identification in determining the driving force of multifactor coupled resistome booming in complicated environmental conditions, thereby paving the way for establishing priority for effective ARGs mitigation strategies.