Mitochondrial DNA Copy Number as a Biomarker for Guiding Adjuvant Chemotherapy in Stages II and III Colorectal Cancer Patients with Mismatch Repair Deficiency: Seeking Benefits and Avoiding Harms.

BACKGROUND: Colorectal cancer (CRC) patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) status are conventionally perceived as unresponsive to adjuvant chemotherapy (ACT). The mitochondrial transcription factor A (TFAM) is required for mitochondrial DNA copy number (mtDNA-CN) expression. In light of previous findings indicating that the frequent truncating-mutation of TFAM affects the chemotherapy resistance of MSI CRC cells, this study aimed to explore the potential of mtDNA-CN as a predictive biomarker for ACT efficacy in dMMR CRC patients. METHODS: Levels of MtDNA-CN were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) in a cohort of 308 CRC patients with dMMR comprising 180 stage II and 128 stage III patients. Clinicopathologic and therapeutic data were collected. The study examined the association between mtDNA-CN levels and prognosis, as well as the impact of ACT benefit on dMMR CRC patients. Subgroup analyses were performed based mainly on tumor stage and mtDNA-CN level. Kaplan-Meier and Cox regression models were used to evaluate the effect of mtDNA-CN on disease-free survival (DFS) and overall survival (OS). RESULTS: A substantial reduction in mtDNA-CN expression was observed in tumor tissue, and higher mtDNA-CN levels were correlated with improved DFS (73.4% vs 85.7%; P = 0.0055) and OS (82.5% vs 90.3%; P = 0.0366) in dMMR CRC patients. Cox regression analysis identified high mtDNA-CN as an independent protective factor for DFS (hazard ratio [HR] 0.547; 95% confidence interval [CI] 0.321-0.934; P = 0.0270) and OS (HR 0.520; 95% CI 0.272-0.998; P = 0.0492). Notably, for dMMR CRC patients with elevated mtDNA-CN, ACT significantly improved DFS (74.6% vs 93.4%; P = 0.0015) and OS (81.0% vs 96.7%; P = 0.0017), including those with stage II or III disease. CONCLUSIONS: The mtDNA-CN levels exhibited a correlation with the prognosis of stage II or III CRC patients with dMMR. Elevated mtDNA-CN emerges as a robust prognostic factor, indicating improved ACT outcomes for stages II and III CRC patients with dMMR. These findings suggest the potential utility of mtDNA-CN as a biomarker for guiding personalized ACT treatment in this population.

LinearAlifold: Linear-time consensus structure prediction for RNA alignments.

Predicting the consensus structure of a set of aligned RNA homologs is a convenient method to find conserved structures in an RNA genome, which has many applications including viral diagnostics and therapeutics. However, the most commonly used tool for this task, RNAalifold, is prohibitively slow for long sequences, due to a cubic scaling with the sequence length, taking over a day on 400 SARS-CoV-2 and SARS-related genomes (∼30,000nt). We present LinearAlifold, a much faster alternative that scales linearly with both the sequence length and the number of sequences, based on our work LinearFold that folds a single RNA in linear time. Our work is orders of magnitude faster than RNAalifold (0.7 h on the above 400 genomes, or ∼36× speedup) and achieves higher accuracies when compared to a database of known structures. More interestingly, LinearAlifold's prediction on SARS-CoV-2 correlates well with experimentally determined structures, substantially outperforming RNAalifold. Finally, LinearAlifold supports two energy models (Vienna and BL*) and four modes: minimum free energy (MFE), maximum expected accuracy (MEA), ThreshKnot, and stochastic sampling, each of which takes under an hour for hundreds of SARS-CoV variants. Our resource is at: https://github.com/LinearFold/LinearAlifold (code) and http://linearfold.org/linear-alifold (server).

Enhancing radiation-resistance and peroxidase-like activity of single-atom copper nanozyme via local coordination manipulation.

The inactivation of natural enzymes by radiation poses a great challenge to their applications for radiotherapy. Single-atom nanozymes (SAzymes) with high structural stability under such extreme conditions become a promising candidate for replacing natural enzymes to shrink tumors. Here, we report a CuN3-centered SAzyme (CuN3-SAzyme) that exhibits higher peroxidase-like catalytic activity than a CuN4-centered counterpart, by locally regulating the coordination environment of single copper sites. Density functional theory calculations reveal that the CuN3 active moiety confers optimal H2O2 adsorption and dissociation properties, thus contributing to high enzymatic activity of CuN3-SAzyme. The introduction of X-ray can improve the kinetics of the decomposition of H2O2 by CuN3-SAzyme. Moreover, CuN3-SAzyme is very stable after a total radiation dose of 500 Gy, without significant changes in its geometrical structure or coordination environment, and simultaneously still retains comparable peroxidase-like activity relative to natural enzymes. Finally, this developed CuN3-SAzyme with remarkable radioresistance can be used as an external field-improved therapeutics for enhancing radio-enzymatic therapy in vitro and in vivo. Overall, this study provides a paradigm for developing SAzymes with improved enzymatic activity through local coordination manipulation and high radioresistance over natural enzymes, for example, as sensitizers for cancer therapy.

Design and optimization of microchannel for enhancement of the intensity of induced signal in particle/cell impedance measurement.

The measured impedance signal of a single particle or cell in a microchannel is of the µA level, which is a challenge for measuring such weak signals. Therefore, it is necessary to improve the intensity for expanding the applications of impedance measurement. In this paper, we analyzed the impact of geometric parameters of microchannel on output signal intensity by using the three-dimensional finite element method. In comparison to conventional microchannels, which are distributed at a uniform height, the microchannels in this design use the height difference to enhance the signal intensity. By analyzing the effects of the geometric dimensions of the constriction channel, main channel height, radius of particles, types of cells, shapes of particles with different ellipticities, and particles spacing on the current signal, we concluded the optimal dimensions of these parameters to improve the intensity of the induced current signal. Through the fabrication of the optimized size of device and experimental demonstration, it is verified that the current signal intensity caused by the particle with a diameter of 10 µm is nearly twice that of the conventional structure with a height of 20 µm, which proves the correctness of the optimization results and the feasibility of this work. In addition, the performance of the device was verified by measuring the mixtures of different size particles as well as non-viable and viable yeast cells.

Zinc proteinate with moderate chelation strength enhances zinc absorption by up-regulating the expression of zinc and amino acid transporters in primary cultured duodenal epithelial cells of broiler embryos.

Recent study showed that zinc (Zn) and amino acid transporters may be involved in enhancing Zn absorption from Zn proteinate with moderate chelation strength (Zn-Prot M) in the duodenum of broilers. However, the specific mechanisms by which Zn-Prot M promotes the above Zn absorption are unknown. Therefore, in this study, three experiments were conducted to investigate specific and direct effects of Zn-Prot M and Zn sulfate (ZnS) on Zn absorption and expression of related transporters in primary duodenal epithelial cells of broiler embryos so as to preliminarily address possible mechanisms. In experiment 1, cells were treated with 100 µmol Zn/L as ZnS or Zn-Prot M for 20, 40, 60, 80, 100 or 120 min. Experiment 2 consisted of 3 sub-experiments. In experiment 2A, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 100 or 200 µmol Zn/L as ZnS or Zn-Prot M for 60 min; in experiment 2B, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 200 µmol Zn/L of as the ZnS or Zn-Prot M for 120 min; in experiment 2C, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 400 or 800 µmol Zn/L as ZnS or Zn-Prot M for 120 min. In experiment 3, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 400 µmol Zn/L as ZnS or Zn-Prot M for 120 min. The results of experiment 1 indicated that the minimum incubation time for saturable Zn absorption was determined to be 50.83 min using the best fit line. The results in experiment 2 demonstrated that a Zn concentration of 400 µmol/L and an incubation time of 120 min were suitable to increase the absorption of Zn from Zn-Prot M compared to ZnS. In experiment 3, Zn absorption across cell monolayers was significantly increased by Zn addition (P < 0.05), and was significantly greater with Zn-Prot M than with ZnS (P < 0.05). Compared to the control, Zn addition significantly decreased Zn transporter 10 and peptide-transporter 1 mRNA expression levels and increased y+L-type amino transporter 2 (y+LAT2) protein abundance (P < 0.05). Moreover, protein expression levels of zrt/irt-like protein 3 (ZIP3), ZIP5 and y+LAT2 were significantly greater for Zn-Prot M than for ZnS (P < 0.05). These findings suggest that Zn-Prot M promote Zn absorption by increasing ZIP3, ZIP5 and y+LAT2 protein expression levels in primary duodenal epithelial cells.

The genomic and immunogenomic landscape of mechanics pathway informs clinical prognosis and response to mechanotherapy.

Mechanics shape cell and tissue plasticity and maintain their homeostasis. In cancers, mechanical signals regulate cancer hallmarks via mechanotransduction pathways, such as proliferation, metastasis and metabolic reprogramming. However, comprehensive characterization of mechanotransduction pathway genes and their clinical relevance across different cancer types remains untouched. Herein, we systematically portrayed the alterations of mechanotransduction pathway genes across 31 cancer types using The Cancer Genome Atlas (TCGA) databases. All the cancer types could be categorized into 6 subtypes based upon the transcriptional pattern of mechanics pathway genes. Each subtype has its own unique molecular expression pattern, mutation landscapes, immune infiltrates, and patient clinical outcome. We further found that the responses of two subtypes of cancers, one with the optimal outcome and the other with the worst prognosis, to a classical mechanotherapeutic agent (Fasudil, RhoA/ROCK inhibitor) were totally different, indicating that our cancer stratification system based upon mechanotransduction pathway genes could inform clinical responses of patients to mechanotherapeutic agents. Collectively, our study provides a novel pan-cancer landscape of the mechanotransduction pathways and underscores its potential clinical significance in the prediction of clinical prognosis and therapeutic responses to mechanotherapy among cancer patients.

Pathophysiological Relevance and Therapeutic Outlook of GPR43 in Atherosclerosis.

Atherosclerosis (AS) is an inflammatory arterial disorder that occurs due to the deposition of the excessive lipoprotein under the artery intima, mainly including low-density lipoprotein (LDL) and other apolipoprotein B-containing lipoproteins. G protein-coupled receptors (GPCRs) play a crucial role in transmitting signals in physiological and pathophysiological conditions. GPCRs recognize inflammatory mediators, thereby serving as important players during chronic inflammatory processes. It has been demonstrated that free fatty acids can function as ligands for various GPCRs, such as free fatty acid receptor (FFAR)1/GPR40, FFAR2/GPR43, FFAR3/GPR41, FFAR4/GPR120, and the lipid metabolite binding glucose-dependent insulinotropic receptor (GPR119). This review discusses GPR43 and its ligands in the pathogenesis of AS, especially focusing on its distinct role in regulating chronic vascular inflammation, inhibiting oxidative stress, ameliorating endothelial dysfunction and improving dyslipidemia. It is hoped that this review may provide guidance for further studies aimed at GPR43 as a promising target for drug development in the prevention and therapy of AS.

Three-stage Dynamic Brain-cognitive Model of Understanding Action Intention Displayed by Human Body Movements.

The ability to comprehend the intention conveyed through human body movements is crucial for effective interpersonal interactions. If people can't understand the intention behind other individuals' isolated or interactive actions, their actions will become meaningless. Psychologists have investigated the cognitive processes and neural representations involved in understanding action intention, yet a cohesive theoretical explanation remains elusive. Hence, we mainly review existing literature related to neural correlates of action intention, and primarily propose a putative Three-stage Dynamic Brain-cognitive Model of understanding action intention, which involves body perception, action identification and intention understanding. Specifically, at the first stage, body parts/shapes are processed by those brain regions such as extrastriate and fusiform body areas; During the second stage, differentiating observed actions relies on configuring relationships between body parts, facilitated by the activation of the Mirror Neuron System; The last stage involves identifying various intention categories, utilizing the Mentalizing System for recruitment, and different activation patterns concerning the nature of the intentions participants dealing with. Finally, we delves into the clinical practice, like intervention training based on a theoretical model for individuals with autism spectrum disorders who encounter difficulties in interpersonal communication.

Changes to circulating tumor cells in the central vein during laparoscopic versus transanal endoscopic surgeries for rectal cancer: can surgical approach make a difference?

Background: The oncological safety of transanal total mesorectal excision (taTME) remains uncertain, and its special surgical approach may contribute to tumor cell dissemination. Thus, we conducted a study to investigate the impact of surgical approach on circulating tumor cell (CTC) counts and phenotypes in rectal cancer. Methods: This is a prospective randomized controlled study (ClinicalTrials: NCT05109130). The patients were randomized to either the taTME (n = 49) or laparoscopic TME (laTME) (n = 48) groups. Blood samples were collected from the central vein to measure CTC counts and phenotypes at three time points: preoperative (t1), immediately post-tumor removal (t2), and one week post-surgery (t3). The effect of surgical procedure on CTCs at each time point was analyzed, with the primary endpoint being the change in CTC counts from t1 to t3 for each surgical approach. This study adheres to Consolidated Standards of Reporting Trials Guidelines. Results: The baseline clinicopathologic characteristics of the laTME and taTME groups were balanced. The change in CTC count from t1 to t3 was 1.81 ± 5.66 in the laTME group and 2.18 ± 5.53 in the taTME group. The taTME surgery was non-inferior to laTME in terms of changing CTC counts (mean difference [MD]: -0.371; 95% confidence interval [CI]: -2.626 to 1.883, upper-sided 95% CI of 1.883 < 2, non-inferiority boundary value). Compared with that at t1, the CTC count at t2 did not change significantly. However, higher CTC counts were detected at t3 than at t2 in the taTME (P = 0.032) and laTME (P = 0.003) groups. From t1 to t3, CTC counts significantly increased in both the taTME (P = 0.008) and laTME (P = 0.031) groups. There were no significant differences in CTC phenotype changes between the two groups from t1 to t3. Conclusions: Compared with laTME, taTME did not affect CTC counts and phenotypes. Our findings indicate that taTME is not inferior to laTME in terms of CTC changes from an oncological perspective.

BmHSP19.9 targeting P6.9 and VLF-1 to mediate the formation of defective progeny viruses in the silkworm antiviral variety 871C.

The 871C silkworm strain exhibits a high level of resistance to Bombyx mori nucleopolyhedrovirus (BmNPV), making it a valuable variety for the sericulture industry. Understanding the underlying mechanism of its resistance holds great biological significance and economic value in addressing viral disease risks in sericulture. Initially, we infected the resistant strain 871C and its control strain 871 with BmNPV and conducted secondary infection experiments using the progeny occlusion bodies (OBs). As a result, a significant decrease in pathogenicity was observed. Electron microscopy analysis revealed that 871C produces progeny virions with defective DNA packaging, reducing virulence following BmNPV infection. Blood proteomic identification of the silkworm variety 871C and control 871 after BmNPV infection demonstrated the crucial role of the viral proteins P6.9 and VLF-1 in the production of defective viruses by impeding the proper encapsulation of viral DNA. Additionally, we discovered that BmHSP19.9 interacts with P6.9 and VLF-1 and that its expression is significantly upregulated after BmNPV infection. BmHSP19.9 exhibits strong antiviral activity, in part by preventing the entry of the proteins P6.9 and VLF-1 into the nucleus, thereby hindering viral nucleocapsid and viral DNA assembly. Our findings indicate that the antiviral silkworm strain 871C inhibits BmNPV proliferation by upregulating Bmhsp19.9 and impeding the nuclear localization of the viral proteins P6.9 and VLF-1, leading to the production of defective viral particles. This study offers a comprehensive analysis of the antiviral mechanism in silkworms from a viral perspective, providing a crucial theoretical foundation for future antiviral research and the breeding of resistant silkworm strains.

Distribution and health risk of chromium in wheat grains at the national scale in China.

Chromium (Cr) pollution may threaten food safety in China. In this study, the concentration, pollution level, distribution, and non-cancer risk of Cr in wheat grains grown in 186 areas across 28 provinces in China were investigated. Results indicated that mean concentration of Cr was 0.28 ± 2.5 mg/kg, dry mass (dm). Of the samples, 7.5 % were found to be polluted with Cr. The mean concentrations were in the following order: Northwest > Northeast > South > East > North > Southwest > Central China. Based on deterministic models, mean hazard quotient (HQ) values for adult males, adult females, and children were 0.11 ± 3.4, 0.11 ± 3.4, and 0.13 ± 3.5, respectively with < 6 % of HQ values ≥ 1. Eleven sites in northern China were identified as hotspots, whereas Gansu Province and Northwestern China were labeled as priority provinces and regions for risk control. The mean HQ values estimated by probabilistic risk assessment were two times greater than those estimated using deterministic models. The risk probabilities for adult males, adult females, and children were 4.81 %, 3.78 %, and 6.55 %, respectively. This study provides valuable information on Cr pollution in wheat grains and its risks at a national scale in China.

Natural Language Processing-Powered Real-Time Monitoring Solution for Vaccine Sentiments and Hesitancy on Social Media: System Development and Validation.

BACKGROUND: Vaccines serve as a crucial public health tool, although vaccine hesitancy continues to pose a significant threat to full vaccine uptake and, consequently, community health. Understanding and tracking vaccine hesitancy is essential for effective public health interventions; however, traditional survey methods present various limitations. OBJECTIVE: This study aimed to create a real-time, natural language processing (NLP)-based tool to assess vaccine sentiment and hesitancy across 3 prominent social media platforms. METHODS: We mined and curated discussions in English from Twitter (subsequently rebranded as X), Reddit, and YouTube social media platforms posted between January 1, 2011, and October 31, 2021, concerning human papillomavirus; measles, mumps, and rubella; and unspecified vaccines. We tested multiple NLP algorithms to classify vaccine sentiment into positive, neutral, or negative and to classify vaccine hesitancy using the World Health Organization's (WHO) 3Cs (confidence, complacency, and convenience) hesitancy model, conceptualizing an online dashboard to illustrate and contextualize trends. RESULTS: We compiled over 86 million discussions. Our top-performing NLP models displayed accuracies ranging from 0.51 to 0.78 for sentiment classification and from 0.69 to 0.91 for hesitancy classification. Explorative analysis on our platform highlighted variations in online activity about vaccine sentiment and hesitancy, suggesting unique patterns for different vaccines. CONCLUSIONS: Our innovative system performs real-time analysis of sentiment and hesitancy on 3 vaccine topics across major social networks, providing crucial trend insights to assist campaigns aimed at enhancing vaccine uptake and public health.

Real-world efficacy and safety of TACE-HAIC combined with TKIs and PD-1 inhibitors in initially unresectable hepatocellular carcinoma.

BACKGROUND: Local treatment may function synergistically with immunotherapy and targeted agents. This study aimed to assess the effectiveness and safety of transcatheter arterial chemoembolization (TACE) and hepatic artery infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and programmed death-1 (PD-1) inhibitors in patients with initially unresectable hepatocellular carcinoma (uHCC). METHODS: A retrospective study was conducted on patients diagnosed with initially uHCC who received combined treatment of TACE-HAIC combined with TKIs and PD-1 inhibitors from July 2020 to February 2023. The primary endpoints were overall survival (OS) and progression free survival (PFS) and adverse events (AEs). Objective response rate (ORR), disease control rate (DCR) and conversion surgery rate (CSR), whereas the secondary endpoints. RESULTS: After screening, a total of 62 patients were selected for this study. The overall median OS was 18.2 (95% CI 16.24-20.16) months and median PFS was 9.2 (95% CI 7.24-11.16) months. Based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and RECIST v1.1 criteria, ORR was 67.7% (42/62), and the DCR was 90.3% (56/62), the CSR was 27.4% (17/62). The most common treatment-emergent adverse events (TEAEs) were transaminitis (56.4%, 35/62), nausea and vomiting (43.5%, 27/62), thrombocytopenia (37.1%, 23/62), abdominal pain (33.9%, 21/62), and fever (33.9%, 21/62). CONCLUSIONS: TKIs combined with PD-1 inhibitors plus TACE-HAIC therapy represents an effective and tolerable treatment option in patients with uHCC. Patients undergoing surgery after combination therapy may have survival benefits.

Isobavachalcone: A redox antifungal agent impairs the mitochondria protein of Cryptococcus neoformans.

Isobavachalcone (IBC) is a natural small molecule with various biological activities; however, its inhibitory effects on Cryptococcus neoformans remain unclear. In our study, IBC showed a good antifungal effect. Through in vitro experiments, its minimum inhibitory concentration was 0.5-1 µg/mL. It exhibited the same antifungal effect as Amphotericin B in brain and lung infections in in vivo experiments. IBC also showed a synergistic antifungal effect with emodin with lower toxicity, and C. neoformans did not develop drug resistance to IBC. In the mechanistic study, significantly damaged mitochondria of C. neoformans, a significant reduction in mitochondrial membrane potential and adenosine triphosphate production, and an increase in hydrogen peroxide (H2O2) caused by IBC were observed using transmission electron microscopy. Through drug affinity-responsive target stability combined with phenotype detection, riboflavin synthases of aconitase and succinate dehydrogenase were screened. Molecular docking, quantitative polymerase chain reaction experiments, target inhibitor and agonist intervention, molecular interaction measurements, and minimum inhibitory concentration detection of the constructed expression strains revealed that IBC targeted the activity of these two enzymes, interfered by the tricarboxylic acid cycle, inhibited the production of adenosine triphosphate, blocked electron transport, reduced mitochondrial membrane potential, and induced antioxidation imbalance and reactive oxygen species accumulation, thus producing an antifungal effect. Therefore, IBC is a promising lead drug and redox antifungal agent for C. neoformans.

Identifying modifiable factors and their joint effect on brain health: an exposome-wide association study.

Considerable uncertainty remains regarding the associations of multiple factors with brain health. We aimed to conduct an exposome-wide association study on neurodegenerative disease and neuropsychiatry disorders using data of participants from the UK Biobank. Multivariable Cox regression models with the least absolute shrinkage and selection operator technique as well as principal component analyses were used to evaluate the exposures in relation to common disorders of central nervous system (CNS). Restricted cubic splines were conducted to explore potential nonlinear correlations. Then, weighted standardized scores were generated based on the coefficients to calculate the joint effects of risk factors. We also estimated the potential impact of eliminating the unfavorable profiles of risk domains on CNS disorders using population attributable fraction (PAF). Finally, sensitivity analyses were performed to reduce the risk of reverse causality. The current study discovered the significantly associated exposures fell into six primary exposome categories. The joint effects of identified risk factors demonstrated higher risks for common disorders of CNS (HR = 1.278 ~ 3.743, p < 2e-16). The PAF varied by exposome categories, with lifestyle and medical history contributing to majority of disease cases. In total, we estimated that up to 3.7 ~ 64.1% of disease cases could be prevented.This study yielded modifiable variables of different categories and assessed their joint effects on common disorders of CNS. Targeting the identified exposures might help formulate effective strategies for maintaining brain health.

Kiwi-Inspired Rational Nanoarchitecture with Intensified and Discrete Magneto-Fluorescent Functionalities for Ultrasensitive Point-of-Care Immunoassay.

Fluorescent lateral flow immunoassays (FLFIA) is a well-established rapid detection technique for quantitative analysis. However, achieving accurate analysis of biomarkers at the pg mL-1 level using FLFIA still poses challenges. Herein, an ultrasensitive FLFIA platform is reported utilizing a kiwi-type magneto-fluorescent silica nanohybrid (designated as MFS) that serves as both a target-enrichment substrate and an optical signal enhancement label. The spatially-layered architecture comprises a Fe3O4 core, an endocarp-fibers like dendritic mesoporous silica, seed-like quantum dots, and a kiwi-flesh like silica matrix. The MFS demonstrates heightened fluorescence brightness, swift magnetic response, excellent size uniformity, and dispersibility in water. Through liquid-phase capturing and fluorescence-enhanced signal amplification, as well as magnetic-enrichment sample amplification and magnetic-separation noise reduction, the MFS-based FLFIA is successfully applied to the detection of cardiac troponin I that achieved a limit of detection at 8.4 pg mL-1, tens of times lower than those of previously published fluorescent and colorimetric lateral flow immunoassays. This work offers insights into the strategic design of magneto-fluorescent synergetic signal amplification on LFIA platform and underscores their prospects in high-sensitive rapid and on-site diagnosis of biomarkers.

Investigation of disinfection failure of flexible gastrointestinal endoscope due to Burkholderia cepacia contamination in irrigation tubing.

BACKGROUND AND AIMS: This study aims to identify the cause of disinfection failure of multiple flexible gastrointestinal endoscopes and to enhance the cleaning and disinfection procedures. METHODS: Samples from endoscopy devices, surrounding objects, cleaning water, automatic sterilizer, and integrated endoscopic washing workstation in a Digestive Endoscopy Center were collected and analyzed for microbial contamination and DNA/gene contents, between May and July 2021. RESULTS: The sample analysis revealed that the sink irrigation tubing of the washing workstation was contaminated with Burkholderia cepacia. After effective disinfection measures, the B. cepacia detection in the disinfected endoscope dropped from 13.23% to 0% (p=0.041). The presence of B. cepacia was confirmed through homology search and gene sequencing. CONCLUSIONS: The primary reason for endoscope disinfection failure is the contamination of the sink irrigation tubing by the B. cepacia bacteria. These findings emphasize the need for thorough cleaning of irrigation tubings in integrated endoscopic washing workstations, which is generally neglected in routine maintanance.

Flexible electronics for heavy metal ion detection in water: a comprehensive review.

Flexible electronics offer a versatile, rapid, cost-effective and portable solution to monitor water contamination, which poses serious threat to the environment and human health. This review paper presents a comprehensive exploration of the versatile platforms of flexible electronics in the context of heavy metal ion detection in water systems. The review overviews of the fundamental principles of heavy metal ion detection, surveys the state-of-the-art materials and fabrication techniques for flexible sensors, analyses key performance metrics and limitations, and discusses future opportunities and challenges. By highlighting recent advances in nanomaterials, polymers, wireless integration, and sustainability, this review aims to serve as an essential resource for researchers, engineers, and policy makers seeking to address the critical challenge of heavy metal contamination in water resources. The versatile promise of flexible electronics is thoroughly elucidated to inspire continued innovation in this emerging technology arena.

CAR T Cell Membrane Camouflaged Nanocatalyst Augments CAR T Cell Therapy Efficacy Against Solid Tumor.

The immunosuppressive tumor microenvironment (TME) reduces the chimeric antigen receptor (CAR) T-cell therapy against solid tumors. Here, a CAR T cell membrane-camouflaged nanocatalyst (ACSP@TCM) is prepared to augment CAR T cell therapy efficacy against solid tumors. ACSP@TCM is prepared by encapsulating core/shell Au/Cu2- xSe and 3-bromopyruvate with a CAR T cell membrane. It is demonstrated that the CAR T cell membrane camouflaging has much better-targeting effect than the homologous tumors cell membrane camouflaging. ACSP@TCM has an appealing synergistic chemodynamic/photothermal therapy (CDT/PTT) effect that can induce the immunogenic cell death (ICD) of NALM 6 cells. Moreover, 3-bromopyruvate can inhibit the efflux of lactic acid by inhibiting the glycolysis process, regulating the acidity of TME, and providing a more favorable environment for the survival of CAR T cells. In addition, the photoacoustic (PA) imaging and computed tomography (CT) imaging performance can guide the ACSP@TCM-mediated tumor therapy. The results demonstrated that the ACSP@TCM significantly enhanced the CAR T cell therapy efficacy against NALM 6 solid tumor mass, and completely eliminated tumors. This work provides an effective tumor strategy for CAR T cell therapy in solid tumors.

Synthesis and Antifungal Activities of Novel Griseofulvin Derivatives as Potential Anti-Phytopathogenic Fungi Agents.

The extensive and repeated application of chemical fungicides results in the rapid development of fungicide resistance. Novel antifungal pesticides are urgently required. Natural products have been considered precious sources of pesticides. It is necessary to discover antifungal pesticides by using natural products. Herein, 42 various griseofulvin derivatives were synthesized. Their antifungal activities were evaluated in vitro. Most of them showed good antifungal activity, especially 3d exhibited a very broad antifungal spectrum and the most significant activities against 7 phytopathogenic fungi. In vivo activity results suggested that 3d protected apples and tomatoes from serious infection by phytopathogenic fungi. These proved that 3d had the potential to be a natural product-derived antiphytopathogenic fungi agent. Furthermore, docking analysis suggested that tubulin might be one of the action sites of 3d. It is reasonable to believe that griseofulvin derivatives are worth further development for the discovery of new pesticides.