Identification of BGN positive fibroblasts as a driving factor for colorectal cancer and development of its related prognostic model combined with machine learning.

BACKGROUND: Numerous studies have indicated that cancer-associated fibroblasts (CAFs) play a crucial role in the progression of colorectal cancer (CRC). However, there are still many unknowns regarding the exact role of CAF subtypes in CRC. METHODS: The data for this study were obtained from bulk, single-cell, and spatial transcriptomic sequencing data. Bioinformatics analysis, in vitro experiments, and machine learning methods were employed to investigate the functional characteristics of CAF subtypes and construct prognostic models. RESULTS: Our study demonstrates that Biglycan (BGN) positive cancer-associated fibroblasts (BGN + Fib) serve as a driver in colorectal cancer (CRC). The proportion of BGN + Fib increases gradually with the progression of CRC, and high infiltration of BGN + Fib is associated with poor prognosis in terms of overall survival (OS) and recurrence-free survival (RFS) in CRC. Downregulation of BGN expression in cancer-associated fibroblasts (CAFs) significantly reduces migration and proliferation of CRC cells. Among 101 combinations of 10 machine learning algorithms, the StepCox[both] + plsRcox combination was utilized to develop a BGN + Fib derived risk signature (BGNFRS). BGNFRS was identified as an independent adverse prognostic factor for CRC OS and RFS, outperforming 92 previously published risk signatures. A Nomogram model constructed based on BGNFRS and clinical-pathological features proved to be a valuable tool for predicting CRC prognosis. CONCLUSION: In summary, our study identified BGN + Fib as drivers of CRC, and the derived BGNFRS was effective in predicting the OS and RFS of CRC patients.

Long Noncoding RNA NEAT1 Enhances Phenotypic and Osteogenic Switching of Vascular Smooth Muscle Cells in Atherosclerosis via Scaffolding EZH2.

Atherosclerosis (AS) is a significant contributor to cardio-cerebrovascular ischemia diseases, resulting in high mortality rates worldwide. During AS, vascular smooth muscle cells (VSMCs) play a crucial role in plaque formation by undergoing phenotypic and osteogenic switching. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has previously been identified as a nuclear regulator that promotes tumorigenesis and metastasis, but its role in regulating VSMCs in AS remains unclear. Our study aimed to investigate the biological functions and specific mechanisms of NEAT1 in regulating VSMCs in AS. We found that NEAT1 was upregulated in the aortas of AS mouse models and dedifferentiated primary VSMCs. Silencing NEAT1 in vitro attenuated the proliferation, migration, and osteogenic differentiation of VSMCs, while NEAT1 overexpression had the opposite effect. Furthermore, NEAT1 promoted VSMC osteogenic differentiation and vascular calcification in both in vivo and in vitro vascular calcification models. We also discovered that NEAT1 directly activates enhancer of zeste homolog 2 (EZH2), an epigenetic enzyme that suppresses the expression of senescence- and antimigration-related genes, by translocating it into nucleus. Cut & tag assay revealed that NEAT1 guides EZH2 to the promoters of senescence-related genes (P16, P21, and TIMP3), methylating local histones to reduce their transcription. Our findings suggest that NEAT1 functions in AS by modulating the epigenetic function of EZH2, which enhances the proliferation, migration, and osteogenic differentiation of VSMCs. This study provides new insights into the molecular mechanisms underlying the pathogenesis of AS and highlights the potential of NEAT1 as a therapeutic target of AS.

[Inhibition of Autophagy Augments the Anticancer Activity of KPT-330 in Mantle Cell Lymphoma Cells].

OBJECTIVE: To investigate the influence of novel CRM1 inhibitor KPT-330 on the autophagy of mantle cell lymphoma (MCL) cells, and effect of KPT-330 on the prolifiration of MCL cells in the presence or absence of autophagy inhibitor. METHODS: CCK-8 assay was used to detect the effect of KPT-330 on MCL cell lines Z-138， Jeko-1， Granta-519， Rec-1. The effect of KPT-330 on autophagy features were determined by detecting acidic vesicular organelles (AVO) by MDC staining under fluorescence microscope and detecting protein expression of LC3B-II assessed by Western blot. Further combined application of lysosomal inhibitor Chloroquine (CQ) was used to observe its effect on the increase of LC3B-Ⅱ caused by KPT-330. CalcuSyn 2.0 software was used to detected the Combination index (CI) of KPT-330 combined with CQ. RESULTS: The proliferation of MCL cell lines （Z-138, Jeko-1, Grant-519, Rec-1） could be inhibited by KPT-330 in a dose-dependent manner (r =0.930, 0.946, 0.691, 0.968 respectively). The number of acidic vesicular organelles (AVO) and the expression of LC3B-II were increased in KPT-330 treated Jeko-1 and Granta-519 cells in a dose-dependent manner (r Jeko-1=0.993, r Granta-519=0.971). LC3B-II protein amounts still increased upon KPT-330 treatment with the existence of lysosomal inhibitor CQ in Jeko-1 and Granta-519 cells, which was higher than CQ or KPT-330 single drug group. The combination of KPT-330 and CQ produced the synergistic effects on cells proliferation inhibition with CalcuSyn 2.0 analysis. CONCLUSION: KPT-330 can inhibit MCL cell proliferation and induce autophagy. KPT-330 combined with autophagy inhibitor CQ could produce synergistic anti MCL effects, providing experimental basis for clinical combination therapy.

It is time to explore the impact of length of gestation and fetal health on the human lifespan.

A recently proposed principal law of lifespan (PLOSP) proposes to extend the whole human lifespan by elongating different life stages. As the preborn stage of a human being, gestation is the foundation for the healthy development of the human body. The antagonistic pleiotropy (AP) theory of aging states that there is a trade-off between early life fitness and late-life mortality. The question is whether slower development during the gestation period would be associated with a longer lifespan. Among all living creatures, the length of the gestation period is highly positively correlated to the length of the lifespan, although such a correlation is thought to be influenced by the body sizes of different species. While examining the relationship between lifespan length and body size within the same species, dogs exhibit a negative correlation between lifespans and body sizes, while there is no such correlation among domestic cats. For humans, most adverse gestational environments shorten the period of gestation, and their impacts are long-term. While many issues remain unsolved, various developmental features have been linked to the conditions during the gestation period. Given that the length of human pregnancies can vary randomly by as long as 5 weeks, it is worth investigating whether a slow steady healthy gestation over a longer period will be related to a longer and healthier lifespan. This article discusses the potential benefits, negative impacts, and challenges of the relative elongation of the gestation period.

Cell death dependent on holins LrgAB repressed by a novel ArsR family regulator CdsR.

The cell death and survival paradox in various biological processes requires clarification. While spore development causes maternal cell death in Bacillus species, the involvement of other cell death pathways in sporulation remains unknown. Here, we identified a novel ArsR family transcriptional regulator, CdsR, and found that the deletion of its encoding gene cdsR causes cell lysis and inhibits sporulation. To our knowledge, this is the first report of an ArsR family transcriptional regulator governing cell death. We found that CdsR directly repressed lrgAB expression. Furthermore, lrgAB overexpression resulted in cell lysis without sporulation, akin to the cdsR mutant, suggesting that LrgAB, a holin-like protein, induces cell death in Bacillus spp. The lrgAB mutation increases abnormal cell numbers during spore development. In conclusion, we propose that a novel repressor is vital for inhibiting LrgAB-dependent cell lysis.

Synergizing Fe2O3 nanoparticles on single atom Fe-N-C for nitrate reduction to ammonia at industrial current densities.

The electrochemical reduction of oxidized nitrogen species enables a pathway for the carbon neutral synthesis of ammonia (NH3). The most oxidized form of nitrogen, nitrate (NO3 -) can be reduced to NH3 via the electrocatalytic nitrate reduction reaction (NO3RR), which has been demonstrated at high selectivity. However, to make NH3 synthesis cost-competitive with current technologies, high NH3 partial current densities (jNH3) must be achieved to reduce the levelized cost of NH3. Here, we leverage the high NO3RR activity of Fe-based materials to synthesize a novel active particle-active support system with Fe2O3 nanoparticles supported on atomically dispersed Fe-N-C. By synergizing the activity of both nanoparticles and single atom sites, the optimized 3xFe2O3/Fe-N-C catalyst demonstrates an ultrahigh NO3RR activity, reaching a maximum jNH3 of 1.95 A cm-2 at a Faradaic efficiency (FE) for NH3 of 100% and an NH3 yield rate over 9 mmol hr-1 cm-2 (at -1.2 V versus RHE). In-situ XANES and post-mortem XPS reveal the importance of a pre-reduction activation step, reducing the surface Fe2O3 (Fe3+) to highly active Fe0 sites, which are maintained during electrolysis, to realize the ultrahigh NO3RR activity. Durability studies demonstrate the robustness of both the Fe2O3 particles and Fe-Nx sites at highly cathodic potentials, maintaining a current of -1.3 A cm-2 over 24 hours, a near unity FENH3 (at -1.0 V versus RHE). This work exhibits an effective and durable active particle-active support system enhancing the performance of the NO3RR, enabling industrially relevant current densities and near 100% selectivity. This article is protected by copyright. All rights reserved.

Surface-Activated Ti3C2Tx Adsorption of Acetylene Black Coupled with Polyaniline as a Signal Tag for the Detection of the ESAT-6 Antigen of Mycobacterium tuberculosis.

Early secretory antigenic target-6 (ESAT-6) is regarded as the most immunogenic protein produced by Mycobacterium tuberculosis, whose detection is of great clinical significance for tuberculosis diagnosis. However, the detection of the ESAT-6 antigen has been hampered by the expensive cost and complex experimental procedures, resulting in low sensitivity. Herein, we developed a titanium carbide (Ti3C2Tx)-based aptasensor for ESAT-6 detection utilizing a triple-signal amplification strategy. First, acetylene black (AB) was immobilized on Ti3C2Tx through a cross-linking reaction to form the Ti3C2Tx-AB-PAn nanocomposite. Meanwhile, AB served as a conductive bridge, and Ti3C2Tx can synergistically promote the electron transfer of PAn. Ti3C2Tx-AB-PAn exhibited outstanding conductivity, high electrochemical signals, and abundant sites for the loading of ESAT-6 binding aptamer II (EBA II) to form a novel signal tag. Second, N-CNTs were adsorbed on NiMn layered double hydride (NiMn LDH) nanoflowers to obtain NiMn LDH/N-CNTs, exhibiting excellent conductivity and preeminent stability to be used as electrode modification materials. Third, the biotinylated EBA (EBA I) was immobilized onto a streptavidin-coated sensing interface, forming an amplification platform for further signal enhancement. More importantly, as a result of the synergistic effect of the triple-signal amplification platform, the aptasensor exhibited a wide detection linear range from 10 fg mL-1 to 100 ng mL-1 and a detection limit of 4.07 fg mL-1 for ESAT-6. We envision that our aptasensor provides a way for the detection of ESAT-6 to assist in the diagnosis of tuberculosis.

A Novel Regulator PepR Regulates the Expression of Dipeptidase Gene pepV in Bacillus thuringiensis.

Bacillus thuringiensis produces insecticidal crystal proteins encoded by cry or cyt genes and targets a variety of insect pests. We previously found that a strong promoter of a DeoR family transcriptional regulator (HD73_5014) can efficiently drive cry1Ac expression in B. thuringiensis HD73. Here, we investigated the regulation of neighbor genes by HD73_5014. The HD73_5014 homologs are widely distributed in Gram-positive bacterial species. Its neighbor genes include pepV, rsuA, and ytgP, which encode dipeptidase, rRNA pseudouridine synthase and polysaccharide biosynthesis protein, respectively. The four open reading frames (ORFs) are organized to be a pepR gene cluster in HD73. RT-PCR analysis revealed that the rsuA and ytgP genes formed a transcriptional unit (rsuA-ytgP operon), while pepV formed a transcriptional unit in HD73. Promoter-lacZ fusion assays showed that the pepV and rsuA-ytgP promoters are regulated by HD73_5014. EMSA experiments showed that HD73_5014 directly binds to the pepV promoter region but not to the rusA-ytgP promoter region. Thus, the HD73_5014 transcriptional regulator, which controls the expression of the dipeptidase pepV, was named PepR (dipeptidase regulator). We also confirmed the direct regulation between PepR and PepV by the increased sensitivity to vancomycin in ΔpepV and ΔpepR mutants compared to HD73.

Coptisine inhibits neointimal hyperplasia through attenuating Pak1/Pak2 signaling in vascular smooth muscle cells without retardation of re-endothelialization.

BACKGROUND AND AIMS: Vascular injury-induced endothelium-denudation and profound vascular smooth muscle cells (VSMCs) proliferation and dis-regulated apoptosis lead to post-angioplasty restenosis. Coptisine (CTS), an isoquinoline alkaloid, has multiple beneficial effects on the cardiovascular system. Recent studies identified it selectively inhibits VSMCs proliferation. However, its effects on neointimal hyperplasia, re-endothelialization, and the underlying mechanisms are still unclear. METHODS: Cell viability was assayed by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and cell counting kit-8 (CCK-8). Cell proliferation and apoptosis were measured by flow cytometry and immunofluorescence of Ki67 and TUNEL. Quantitative phosphoproteomics (QPP) was employed to screen CTS-responsive phosphor-sites in the key regulators of cell proliferation and apoptosis. Neointimal hyperplasia was induced by balloon injury of rat left carotid artery (LCA). Adenoviral gene transfer was conducted in both cultured cells and LCA. Re-endothelialization was evaluated by Evan's blue staining of LCA. RESULTS: 1) CTS had strong anti-proliferative and pro-apoptotic effects in cultured rat VSMCs, with the EC50 4∼10-folds lower than that in endothelial cells (ECs). 2) Rats administered with CTS, either locally to LCA's periadventitial space or orally, demonstrated a potently inhibited balloon injury-induced neointimal hyperplasia, but had no delaying effect on re-endothelialization. 3) The QPP results revealed that the phosphorylation levels of Pak1S144/S203, Pak2S20/S197, Erk1T202/Y204, Erk2T185/Y187, and BadS136 were significantly decreased in VSMCs by CTS. 4) Adenoviral expression of phosphomimetic mutants Pak1D144/D203/Pak2D20/D197 enhanced Pak1/2 activities, stimulated the downstream pErk1T202/Y204/pErk2T185/Y187/pErk3S189/pBadS136, attenuated CTS-mediated inhibition of VSMCs proliferation and promotion of apoptosis in vitro, and potentiated neointimal hyperplasia in vivo. 5) Adenoviral expression of phosphoresistant mutants Pak1A144/A203/Pak2A20/A197 inactivated Pak1/2 and totally simulated the inhibitory effects of CTS on platelet-derived growth factor (PDGF)-stimulated VSMCs proliferation and PDGF-inhibited apoptosis in vitro and neointimal hyperplasia in vivo. 6) LCA injury significantly enhanced the endogenous phosphorylation levels of all but pBadS136. CTS markedly attenuated all the enhanced levels. CONCLUSIONS: These results indicate that CTS is a promising medicine for prevention of post-angioplasty restenosis without adverse impact on re-endothelialization. CTS-directed suppression of pPak1S144/S203/pPak2S20/S197 and the subsequent effects on downstream pErk1T202/Y204/pErk2T185/Y187/pErk3S189 and pBadS136 underline its mechanisms of inhibition of VSMCs proliferation and stimulation of apoptosis. Therefore, the phosphor-sites of Pak1S144/S203/Pak2S20/S197 constitute a potential drug-screening target for fighting neointimal hyperplasia restenosis.

Global burden of diseases attributable to intimate partner violence: findings from the Global Burden of Disease Study 2019.

PURPOSE: Our study aims to evaluate the global burden of disease attributable to IPV from 1990 to 2019 at global, regional, national, and socio-demographic index (SDI) levels. Our research question is: What is the global burden of disease attributable to intimate partner violence (IPV) from 1990 to 2019, and how does it vary at global, regional, national, and socio-demographic index (SDI) levels? METHODS: Data parameters for the number of deaths, disability-adjusted life years (DALYs), and age-standardized rate were obtained from the Global Burden of Disease Study 2019. We calculated the percentage change and population attributable fraction with 95% uncertainty intervals. RESULTS: IPV directly accounted for 0.14% [95% UI 0.09%, 0.21%] and 0.32% [95% UI 0.17%, 0.49%] of global all-cause deaths and DALYs in 2019, respectively. The age-standardized deaths and DALYs rates of IPV increased by 12.83% and 4.00% respectively from 1990 to 2019. Women aged 35-39 and 30-34 had the highest deaths and DALYs rate respectively. The highest age-standardized rates of IPV-related deaths and DALYs were observed in Southern Sub-Saharan. Both of deaths and DALYs were high in low-socio-demographic Index (SDI) quintile in 2019. CONCLUSIONS: A higher level of deaths and DALYs attributable to IPV were reported in younger women, in the early 2000s, in Southern Sub-Saharan regions and in low SDI regions. Our study provides policymakers with up-to-date and comprehensive information.

Ferroptosis mechanisms and its novel potential therapeutic targets for DLBCL.

Diffuse large B-cell lymphoma (DLBCL), a heterogeneous lymphoid malignancy, poses a significant threat to human health. The standard therapeutic regimen for patients with DLBCL is rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), with a typical cure rate of 50-70%. However, some patients either relapse after complete remission (CR) or exhibit resistance to R-CHOP treatment. Therefore, novel therapeutic approaches are imperative for managing high-risk or refractory DLBCL. Ferroptosis is driven by iron-dependent phospholipid peroxidation, a process that relies on the transition metal iron, reactive oxygen species (ROS), and phospholipids containing polyunsaturated fatty acids-containing phospholipids (PUFA-PLs). Research indicates that ferroptosis is implicated in various carcinogenic and anticancer pathways. Several hematological disorders exhibit heightened sensitivity to cell death induced by ferroptosis. DLBCL cells, in particular, demonstrate an increased demand for iron and an upregulation in the expression of fatty acid synthase. Additionally, there exists a correlation between ferroptosis-associated genes and the prognosis of DLBCL. Therefore, ferroptosis may be a promising novel target for DLBCL therapy. In this review, we elucidate ferroptosis mechanisms, its role in DLBCL, and the potential therapeutic targets in DLBCL. This review offers novel insights into the application of ferroptosis in treatment strategies for DLBCL.

Azacitidine combined with venetoclax alleviates AML-MR with TP53 mutation in SDS: a case report and literature review.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive genetic disease, which is prone to transform into myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). TP53 mutation is a driving factor involved in the transformation of SDS into MDS/AML, and in the evolution of MDS to AML. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is the only curable approach, however, challenge remains regarding the balance between efficacy and the high risk from treatment-related toxicity and mortality to achieve temporary disease control before transplantation to gain time and opportunities for transplantation. At present, pre-transplant bridging therapy has emerged as one of the important options with improved efficacy, reduced tumor burden, and less treatment-related toxicity. Here we reported azacitidine combined with venetoclax was used as pre-transplant bridging regimen in a TP53-mutant AML-MR case developed from SDS. He achieved complete remission with incomplete recovery and proceeded to Allo-HSCT. We hope to provide some evidence and insight for in-depth research and clinical treatment by presenting this case.

Treatment of lung cancer by acupuncture combined with medicine based on pathophysiological mechanism: A review.

Lung cancer is one of the most frequently diagnosed cancers in the world. There are an estimated 2.2 million new cases and 1.79 million deaths each year. Over the past 2 decades, our understanding of disease biology, the use of predictive biomarkers, and improvements in therapeutic approaches have made significant progress and transformed the outcomes of many patients. Treatment is determined by the subtype and stage of the cancer; however, the effect of personalized treatment remains unsatisfactory. The use of Chinese medicines has attracted increasing attention worldwide. Chinese medicine treatment of lung cancer has few side effects, which can effectively prolong the survival expectation of patients and improve their quality of life, and has attracted increasing attention. Based on the pathophysiological mechanism of lung cancer reported in modern medical research, this article explores the efficacy and safety of acupuncture combined with medicine in the treatment of lung cancer.

Association analysis of the sorting nexin 29 (SNX29) gene copy number variations with growth traits in Diannan small-ear (DSE) pigs.

SNX29 is a potential functional gene associated with meat production traits. Previous studies have shown that SNX29 copy number variation (CNV) could be implicated with phenotype in goats. However, in Diannan small-ear (DSE) pigs, the genetic impact of SNX29 CNV on growth traits remains unclear. Therefore, this study investigated the associations between SNX29 CNVs (CNV10810 and CNV10811) and growth traits in 415 DSE pigs. The results revealed that the CNV10810 mutation was significantly associated with backfat thickness in DSE pigs at 12 and 15 months old (P < 0.05), while the CNV10811 mutation had significant effects on various growth traits at 6 and 12 months old, particularly for body weight, body height, back height and backfat thickness (P < 0.05 or P < 0.001). In conclusion, our results confirm that SNX29 CNV plays a role in regulating growth and development in pigs, thus suggesting its potential application for pig breeding programmes.

Identification of cuproptosis-related lncRNAs with the significance in prognosis and immunotherapy of oral squamous cell carcinoma.

Cuproptosis, a recently characterized programmed cell death mechanism, has emerged as a potential contributor to tumorigenesis, metastasis, and immune modulation. Long non-coding RNAs (lncRNAs) have demonstrated diverse regulatory roles in cancer and hold promise as biomarkers. However, the involvement and prognostic significance of cuproptosis-related lncRNAs (CRLs) in oral squamous cell carcinoma (OSCC) remain poorly understood. Based on TCGA-OSCC data, we integrated single-sample gene set enrichment analysis (ssGSEA), the LASSO algorithm, and the tumor immune dysfunction and exclusion (TIDE) algorithm. We identified 11 CRLs through differential expression, Spearman correlation, and univariate Cox regression analyses. Two distinct CRL-related subtypes were unveiled, delineating divergent survival patterns, tumor microenvironments (TME), and mutation profiles. A robust CRL-based signature (including AC107027.3, AC008011.2, MYOSLID, AC005785.1, AC019080.5, AC020558.2, AC025265.1, FAM27E3, and LINC02367) prognosticated OSCC outcomes, immunotherapy responses, and anti-tumor strategies. Superior predictive power compared to other lncRNA models was demonstrated. Functional assessments confirmed the influence of FAM27E3, LINC02367, and MYOSLID knockdown on OSCC cell behaviors. Remarkably, the CRLs-based signature maintained stability across OSCC patient subgroups, underscoring its clinical potential for survival prediction. This study elucidates CRLs' roles in TME of OSCC and establishes a potential signature for precision therapy.

Differential inflammation responses determine the variable phenotypes of epilepsy induced by GABRG2 mutations.

OBJECTIVE: To explore the mechanism involved in variable phenotypes of epilepsy models induced by γ-aminobutyric acid type A γ2 subunit (GABRG2) mutations. METHODS: The zebrafish carrying wild-type (WT) GABRG2, mutant GABRG2(P282S), GABRG2(F343L) and GABRG2(I107T) were established by Tol2kit transgenesis system and Gateway method. Behavioral analysis of different transgenic zebrafish was performed with the DanioVision Video-Track framework and the brain activity was analyzed by field potential recording with MD3000 Bio-signal Acquisition and Processing System. The transcriptome analysis was applied to detect the underlying mechanisms of variable phenotypes caused by different GABRG2 mutations. RESULTS: The established Tg(hGABRG2P282S ) zebrafish showed hyperactivity and spontaneous seizures, which were more sensitive to chemical and physical epileptic stimulations. Traditional antiepileptic drugs, such as Clonazepam (CBZ) and valproic acid (VPA), could ameliorate the hyperactivity in Tg(hGABRG2P282S ) zebrafish. The metabolic pathway was significantly changed in the brain transcriptome of Tg(hGABRG2P282S ) zebrafish. In addition, the behavioral activity, production of pro-inflammatory factors, and activation of the IL-2 receptor signal pathway varied among the three mutant zebrafish lines. CONCLUSION: We successfully established transgenic zebrafish epileptic models expressing human mutant GABRG2(P282S), in which CBZ and VPA showed antiepileptic effects. Differential inflammatory responses, especially the SOCS/JAK/STAT signaling pathway, might be related to the phenotypes of genetic epilepsy induced by GABRG2 mutations. Further study will expand the pathological mechanisms of genetic epilepsies and provide a theoretical basis for searching for effective drug treatment.

Eco-friendly hydrophobic ZIF-8/sodium alginate monolithic adsorbent: An efficient trap for microplastics in the aqueous environment.

Microplastics (MPs), a newly emerging class of environmental contaminants, pose a severe threat to the entire ecosystem. The development of efficient and environmentally responsible adsorbents for removing the MPs is a particularly urgent research. Herein, a kind of monolithic ZIF-8 based adsorbents featuring stable hydrophobicity and micropore-mesopore-macropore hierarchical porous structure were fabricated by in situ growth of ZIF-8 nanoparticles on sodium alginate (SA) framework, and using polydimethylsiloxane (PDMS) as a hydrophobic agent. The monolithic nature of ZIF-8/SA allowed an easy solid-liquid separation process for adsorbents from water environment compared to powdered materials. The hierarchical porous structure ensures a remarkable MPs removal performance. The ZIF-8/SA showed high adsorption capacities of 594, 585, and 282 mg/g for polymethyl methacrylate (PMMA), poly (vinylidene difluoride) (PVDF), and polyvinyl chloride (PVC) respectively, and rapid adsorption kinetic progress within 120 min. The ZIF-8/SA adsorbents also exhibited excellent stability in the presence of interfering ions, acid/alkali, and humic acid, and displayed adsorption performance of > 70 % even in actual aquatic environment such as tap water, river water, and seawater. The results of characterizations showed that the synergistic effect of electrostatic interaction, hydrogen bonding, hydrophobic force, and van der Waals force was the main adsorption mechanism. The well-designed hydrophobic ZIF-8/SA monolithic materials would be promising to rapidly remove the MPs from the water environment.

Using Vision Transformer for high robustness and generalization in predicting EGFR mutation status in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a common cause of cancer-related deaths worldwide, and accurate EGFR genotyping is crucial for optimal treatment outcomes. Conventional methods for identifying the EGFR genotype have several limitations. Therefore, we proposed a deep learning model using non-invasive CT images to predict EGFR mutation status with robustness and generalizability. METHODS: A total of 525 patients were enrolled at the local hospital to serve as the internal data set for model training and validation. In addition, a cohort of 30 patients from the publicly available Cancer Imaging Archive Data Set was selected for external testing. All patients underwent plain chest CT, and their EGFR mutation status labels were categorized as either mutant or wild type. The CT images were analyzed using a self-attention-based ViT-B/16 model to predict the EGFR mutation status, and the model's performance was evaluated. To produce an attention map indicating the suspicious locations of EGFR mutations, Grad-CAM was utilized. RESULTS: The ViT deep learning model achieved impressive results, with an accuracy of 0.848, an AUC of 0.868, a sensitivity of 0.924, and a specificity of 0.718 on the validation cohort. Furthermore, in the external test cohort, the model achieved comparable performances, with an accuracy of 0.833, an AUC of 0.885, a sensitivity of 0.900, and a specificity of 0.800. CONCLUSIONS: The ViT model demonstrates a high level of accuracy in predicting the EGFR mutation status of lung adenocarcinoma patients. Moreover, with the aid of attention maps, the model can assist clinicians in making informed clinical decisions.

Patient-centered and integrated outreach care for chronic hepatitis C patients with serious mental illness in Taiwan.

Patients with serious mental illness have a higher risk of hepatitis C virus (HCV) infection but suboptimal HCV care. The current study aimed to facilitate HCV treatment uptake by implementing an integrated outreach care model. Multidisciplinary outreach screening followed by HCV reflex testing and onsite treatment for schizophrenia patients was accomplished through the coordination of nongovernmental organizations, remote specialists, and local care providers. The objective was microelimination effectiveness, defined as the multiplication of the rates of anti-HCV antibodies screening, accurate HCV RNA diagnosis, treatment allocation, treatment completion, and sustained virological response (SVR12; no detectable HCV RNA throughout 12 weeks in the post-treatment follow-up period). A total of 1478 of the 2300 (64.3%) psychiatric patients received HCV mass screening. Seventy-three (4.9%) individuals were seropositive for anti-HCV antibodies. Of the 73 anti-HCV seropositive patients, all (100%) received HCV reflex testing, and 29 (37.7%) patients had HCV viremia. Eight patients (34.8%) had advanced liver disease, including 3 with liver cirrhosis and 2 with newly diagnosed hepatocellular carcinoma. Twenty-three of the 24 (95.8%) patients who stayed in the healthcare system received and completed 8 weeks of glecaprevir/pibrentasvir treatment and post-treatment follow-up without significant DDIs or adverse events. The SVR12 rate was 100%. The microelimination effectiveness in the current study was 61.6%. Individuals with serious mental illness are underserved and suffer from diagnostic delays. This patient-centered and integrated outreach program facilitated HCV care in this marginalized population.

Early identification of delayed wound healing in complex diabetic foot ulcers treated with a dermal regeneration template: a novel clinical target and its risk factors.

BACKGROUND: The dermal regeneration template (DRT), a tissue-engineered skin substitute composing a permanent dermal matrix and an upper temporary silicone layer that serves as the epidermis, has demonstrated efficacy in treating uncomplicated diabetic foot ulcers (DFUs). Our institution has obtained good outcomes with DRT in patients with more complicated DFUs. Because of its chronicity, the authors are working to identify a clinical target that anticipates delayed healing early in the treatment in addition to determining the risk factors linked to this endpoint to increase prevention. MATERIALS AND METHODS: This retrospective single-center study analyzed patients with DFUs who underwent wound reconstruction using DRT between 2016 and 2021. The patients were categorized into poor or good graft-take groups based on their DRT status on the 21st day after the application. Their relationship with complete healing (CH) rate at day 180 was analyzed. Variables were collected for risk factors for poor graft take at day 21. Independent risk factors were identified after multivariable analysis. The causes of poor graft take were also reported. RESULTS: This study examined 80 patients (38 and 42 patients in the poor and good graft-take groups, respectively). On day 180, the CH rate was 86.3% overall, but the poor graft-take group had a significantly lower CH rate (76.3 vs. 95.2%, P =0.021) than the good graft-take group. Our analysis identified four independent risk factors: transcutaneous oxygen pressure less than 30 mmHg (odds ratio, 154.14), off-loading device usage (0.03), diabetic neuropathy (6.51), and toe wound (0.20). The most frequent cause of poor graft take was infection (44.7%), followed by vascular compromise (21.1%) and hematoma (15.8%). CONCLUSION: Our study introduces the novel concept of poor graft take at day 21 associated with delayed wound healing. Four independent risk factors were identified, which allows physicians to arrange interventions to mitigate their effects or select patients more precisely. DRT represents a viable alternative to address DFUs, even in complicated wounds. A subsequent split-thickness skin graft is not always necessary to achieve CH.