Genome-wide CRISPR/Cas9 library screen identifies C16orf62 as a host dependency factor for porcine deltacoronavirus infection.

ABSTRACTPorcine deltacoronavirus (PDCoV) is an emerging pathogen that can cause severe diarrhea and high mortality in suckling piglets. Moreover, evidence of PDCoV infection in humans has raised concerns regarding potential public health risks. To identify potential therapeutic targets for PDCoV, we performed a genome-wide CRISPR/Cas9 library screening to find key host factors important to PDCoV infection. Several host genes in this screen were enriched, including ANPEP, which encodes the PDCoV receptor aminopeptidase N (APN). Furthermore, we discovered C16orf62, also known as the VPS35 endosomal protein sorting factor like (VPS35L), as an important host factor required for PDCoV infection. C16orf62 is an important component of the multiprotein retriever complex involved in protein recycling in the endosomal compartment and its gene knockout led to a remarkable decrease in the binding and internalization of PDCoV into host cells. While we did not find evidence for direct interaction between C16orf62 and the viral s (spike) protein, C16orf62 gene knockout was shown to downregulate APN expression at the cell surface. This study marks the first instance of a genome-wide CRISPR/Cas9-based screen tailored for PDCoV, revealing C16orf62 as a host factor required for PDCoV replication. These insights may provide promising avenues for the development of antiviral drugs against PDCoV infection.

Chinese expert consensus on management of antifungal-resistant dermatophytoses (2024 edition).

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal⁃Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.

Dynamic analysis of a novel hyperchaotic system based on STM32 and application in image encryption.

This paper presents a novel 4D hyperchaotic system derived from a modified 3D Lorenz chaotic system. A key aspect of this system is the presence of a single equilibrium point, and its stability is carefully analyzed. The dynamic properties, including the Lyapunov exponent spectrum, bifurcation diagram, and chaotic attractors, are investigated using MATLAB simulations. The results reveal that the system displays hyperchaotic behavior across a wide range of the parameter d , with its chaotic attractor transitioning through four states: hyperchaotic, chaotic, periodic, and quasi-periodic, showcasing the system's complex dynamics. Experimental validation using STM32 embedded hardware successfully reproduces these four types of chaotic attractors, confirming the theoretical predictions. The proposed hyperchaotic system is then applied to image encryption, introducing a novel encryption method. The hyperchaotic key sequence generated by this system meets 15 tests of the NIST SP800-22 standard, and further experimental validation with STM32 hardware demonstrates the algorithm's effectiveness, simplicity, non-linearity, and high security. The encrypted images and sequences are rigorously tested key space analysis, histogram similarity analysis, information entropy analysis, statistical attack analysis, differential attack analysis, key sensitivity analysis, and correlation analysis, highlighting the robustness and reliability of the proposed system. This method is versatile and can be extended to various fields, including audio and video encryption, text encryption, IoT security, financial transaction security, and medical data protection.

The Generation and Characterization of Monoclonal Antibodies against the MPXV A29L Protein.

Mpox (formerly known as monkeypox) is a zoonotic disease caused by monkeypox virus (MPXV), a DNA virus belonging to the Orthopoxvirus genus, in the Poxviridae family. The disease constitutes a moderate risk to public health at the global level. The MPXV A29L protein plays a crucial role in coordinating virion assembly and facilitating important virus-host interactions. This study focused on the expression, purification, and recombinant protein synthesis of the A29L protein of MPXV using prokaryotic systems. Using hybridoma technology, we successfully generated the monoclonal antibodies (mAbs) 1E12 and 4B2, which specifically recognize the A29L protein. These mAbs were found to be suitable for use in indirect immunofluorescence assays (IFA), Western blotting, and immunoprecipitation (IP). Our investigation also revealed that mAbs 1E12 and 4B2 could detect the A27L protein, a homologous protein found in the vaccinia virus Western Reserve (VACV WR) strain, using IFA, Western blotting, and immunoprecipitation (IP). Using mAbs 1E12 and 4B2 as primary immunological probes, A27L protein expression was detected as early as 6 h postinfection with VACV WR, with increasing protein levels being observed throughout the infection. This study enhances our understanding of the protein structure and function of MPXV and contributes to the development of specific MPXV detection methods.

Identification of 7-aminourea or 7-aminothiourea derivatives of camptothecin as selective topoisomerase I inhibitors with anti-colorectal cancer activities.

Colorectal cancer (CRC) remains one of the most prevalent malignant tumors of the digestive system, yet the availability of safe and effective chemotherapeutic agents for clinical use remains limited. Camptothecin (CPT) and its derivatives, though approved for cancer treatment, have encountered significant challenges in clinical application due to their low bioavailability and high systemic toxicity. Strategic modification at the 7-position of CPT enables the development of novel CPT derivatives with high activity. In the present study, a series of compounds incorporating aminoureas, amino thioureas, and acylamino thioureas as substituents at the 7-position were screened. These compounds were subsequently evaluated for their cytotoxicity against the human gastric cancer (GC) cell line AGS and the CRC cell line HCT116. Two derivatives, XSJ05 (IC50 = 0.006 ± 0.003 µM) and XSJ07 (IC50 = 0.013 ± 0.003 µM), exhibited remarkably effective anti-CRC activity, being better than TPT. In addition, they have a better safety profile. In vitro mechanistic studies revealed that XSJ05 and XSJ07 exerted their inhibitory effects on CRC cell proliferation by suppressing the activity of topoisomerase I (Topo I). This suppression triggers DNA double-strand breaks, leads to DNA damage and subsequently causes CRC cells to arrest in the G2/M phase. Ultimately, the cells undergo apoptosis. Collectively, these findings indicate that XSJ05 and XSJ07 possess superior activity coupled with favorable safety profiles, suggesting their potential as lead compounds for the development of CRC therapeutics.

AsmMix: an efficient haplotype-resolved hybrid de novo genome assembling pipeline.

Accurate haplotyping facilitates distinguishing allele-specific expression, identifying cis-regulatory elements, and characterizing genomic variations, which enables more precise investigations into the relationship between genotype and phenotype. Recent advances in third-generation single-molecule long read and synthetic co-barcoded read sequencing techniques have harnessed long-range information to simplify the assembly graph and improve assembly genomic sequence. However, it remains methodologically challenging to reconstruct the complete haplotypes due to high sequencing error rates of long reads and limited capturing efficiency of co-barcoded reads. We here present a pipeline, AsmMix, for generating both contiguous and accurate diploid genomes. It first assembles co-barcoded reads to generate accurate haplotype-resolved assemblies that may contain many gaps, while the long-read assembly is contiguous but susceptible to errors. Then two assembly sets are integrated into haplotype-resolved assemblies with reduced misassembles. Through extensive evaluation on multiple synthetic datasets, AsmMix consistently demonstrates high precision and recall rates for haplotyping across diverse sequencing platforms, coverage depths, read lengths, and read accuracies, significantly outperforming other existing tools in the field. Furthermore, we validate the effectiveness of our pipeline using a human whole genome dataset (HG002), and produce highly contiguous, accurate, and haplotype-resolved assemblies. These assemblies are evaluated using the GIAB benchmarks, confirming the accuracy of variant calling. Our results demonstrate that AsmMix offers a straightforward yet highly efficient approach that effectively leverages both long reads and co-barcoded reads for haplotype-resolved assembly.

Association of early-term birth and breastfeeding practices with nutritional outcomes in singleton term infants: a multicenter cross-sectional study.

BACKGROUND: Limited research has explored the associations of gestational age (GA) and breastfeeding practices with growth and nutrition in term infants. METHODS: This multicenter cross-sectional study recruited 7299 singleton term infants from well-child visits in Shandong, China, between March 2021 and November 2022. Data on GA, gender, ethnicity, birth weight, parental heights, gestational diabetes and hypertension, age at visit, breastfeeding practices (point-in-time data at visit for infants < 6 months and retrospective data at 6 months for infants ≥ 6 months), complementary foods introduction, infant length and weight, were collected. 7270 infants were included in the analysis after excluding outliers with Z-scores of length (LAZ), weight or weight for length (WLZ) <-4 or > 4. Linear regression models adjused for covariates explored the impact of GA and breastfeeding practices on LAZ and WLZ, while logistic regression models evaluated their effect on the likelihood of moderate and severe stunting (MSS, LAZ<-2), moderate and severe acute malnutrition (MSAM, WLZ<-2) and overweight/obesity (WLZ > 2). Sensitivity analysis was conducted on normal birth weight infants (2.5-4.0 kg). RESULTS: Infants born early-term and exclusively breastfed accounted for 31.1% and 66.4% of the sample, respectively. Early-term birth related to higher WLZ (< 6 months: ß = 0.23, 95% confidence interval (CI): 0.16, 0.29; ≥6 months: ß = 0.12, 95% CI: 0.04, 0.20) and an increased risk of overweight/obesity throughout infancy (< 6 months: OR: 1.41, 95% CI 1.08, 1.84; ≥6 months: OR: 1.35, 95% CI 1.03, 1.79). Before 6 months, early-term birth correlated with lower LAZ (ß=-0.16, 95% CI: -0.21, -0.11) and an increased risk of MSS (OR: 1.01, 95%CI 1.00, 1.02); Compared to exclusive breastfeeding, exclusive formula-feeding and mixed feeding linked to lower WLZ (ß=-0.15, 95%CI -0.30, 0.00 and ß=-0.12, 95%CI -0.19, -0.05, respectively) and increased risks of MSAM (OR: 5.57, 95%CI 1.95, 15.88 and OR: 3.19, 95%CI 1.64, 6.19, respectively). Sensitivity analyses confirmed these findings. CONCLUSIONS: The findings emphasize the health risks of early-term birth and the protective effect of exclusive breastfeeding in singleton term infants, underscoring the avoidance of nonmedically indicated delivery before 39 weeks and promoting exclusive breastfeeding before 6 months.

Synthesis and Biological Activity of 2-Chloro-8-methoxy-5-methyl-5H-indolo [2,3-b] Quinoline for the Treatment of Colorectal Cancer by Modulating PI3K/AKT/mTOR Pathways.

Developing novel drugs from natural products has proven to be a very effective strategy. Neocryptolepine was isolated from Cryptolepis sanguinolenta, a traditional endemic African herb, which exerts a wide range of biological activities such as antimalaria, antibacterial, and antitumor. 2-Chloro-8-methoxy-5-methyl-5H-indolo [2,3-b] quinoline (compound 49) was synthesized, and its cytotoxicity was assessed on pancreatic cancer PANC-1 cells, colorectal cancer HCT116 cells, liver cancer SMMC-7721 cells, and gastric cancer AGS cells in vitro. The results of the in vitro assay showed that compound 49 exerted remarkable cytotoxicity on colorectal cancer HCT116 and Caco-2 cells. The cytotoxicity of compound 49 to colorectal cancer HCT116 cells was 17 times higher than that of neocryptolepine and to human normal intestinal epithelial HIEC cells was significantly reduced. Compound 49 exhibited significant cytotoxicity against the colorectal cancer HCT116 and Caco-2 cells, with IC50 of 0.35 and 0.54 µM, respectively. The mechanism of cytotoxicity of compound 49 to colorectal cancer HCT116 and Caco-2 cells was further investigated. The results showed that compound 49 could inhibit colony formation and cell migration. Moreover, compound 49 could arrest the cell cycle at the G2/M phase, promote the production of reactive oxygen species, reduce mitochondrial membrane potential, and induce apoptosis. The results of Western blot indicated that compound 49 showed cytotoxicity on HCT116 and Caco-2 cells by modulating the PI3K/AKT/mTOR signaling pathway. In conclusion, these results suggested that compound 49 may be a potentially promising lead compound for the treatment of colorectal cancer.

Corrigendum: Gut microbiome alterations during gastric cancer: evidence assessment of case-control studies.

[This corrects the article DOI: 10.3389/fmicb.2024.1406526.].

The RP11-417E7.1/THBS2 signaling pathway promotes colorectal cancer metastasis by activating the Wnt/ß-catenin pathway and facilitating exosome-mediated M2 macrophage polarization.

BACKGROUND: Metastasis is the major cause of colorectal cancer (CRC) mortality. Emerging evidence suggests that long noncoding RNAs (lncRNAs) drive cancer metastasis and that their regulatory pathways could be targeted for preventing metastasis. However, the underlying mechanisms of lncRNAs in CRC metastasis remain poorly understood. METHODS: Microarray analysis was used to screen for differentially expressed lncRNAs. Transwell assays, fibronectin cell adhesion assays, and mouse metastasis models were utilized to evaluate the metastatic capacities of CRC in vitro and in vivo. Chromatin isolation by RNA purification, chromatin immunoprecipitation and chromosome conformation capture were applied to investigate the underlying mechanism involved. qRT‒PCR and transmission electron microscopy were performed to confirm macrophage polarization and the presence of cancer-derived exosomes. RESULTS: The lncRNA RP11-417E7.1 was screened and identified as a novel metastasis-associated lncRNA that was correlated with a poor prognosis. RP11-417E7.1 enhances the metastatic capacity of CRC cells in vivo and in vitro. Mechanistically, RP11-417E7.1 binding with High mobility group A1 (HMGA1) promotes neighboring thrombospondin 2 (THBS2) transcription via chromatin loop formation between its promoter and enhancer, which activates the Wnt/ß-catenin signaling pathway and facilitates CRC metastasis. Furthermore, exosomes derived from CRC cells transport THBS2 into macrophages, thereby inducing the M2 polarization of macrophages to sustain the prometastatic microenvironment. Notably, netropsin, a DNA-binding drug, suppresses chromatin loop formation mediated by RP11-417E7.1 at the THBS2 locus and significantly inhibits CRC metastasis in vitro and in vivo. CONCLUSIONS: This study revealed the novel prometastatic function and mechanism of the lncRNA RP11-417E7.1, which provides a potential prognostic indicator and therapeutic target in CRC.

Metabolomics Reveals the Impact of Overexpression of Cytosolic Fructose-1,6-Bisphosphatase on Photosynthesis and Growth in Nannochloropsis gaditana.

Nannochloropsis gaditana, a microalga known for its photosynthetic efficiency, serves as a cell factory, producing valuable biomolecules such as proteins, lipids, and pigments. These components make it an ideal candidate for biofuel production and pharmaceutical applications. In this study, we genetically engineered N. gaditana to overexpress the enzyme fructose-1,6-bisphosphatase (cyFBPase) using the Hsp promoter, aiming to enhance sugar metabolism and biomass accumulation. The modified algal strain, termed NgFBP, exhibited a 1.34-fold increase in cyFBPase activity under photoautotrophic conditions. This modification led to a doubling of biomass production and an increase in eicosapentaenoic acid (EPA) content in fatty acids to 20.78-23.08%. Additionally, the genetic alteration activated the pathways related to glycine, protoporphyrin, thioglucosides, pantothenic acid, CoA, and glycerophospholipids. This shift in carbon allocation towards chloroplast development significantly enhanced photosynthesis and growth. The outcomes of this study not only improve our understanding of photosynthesis and carbon allocation in N. gaditana but also suggest new biotechnological methods to optimize biomass yield and compound production in microalgae.

AQP1 Deficiency Drives Phthalate-Induced Epithelial Barrier Disruption through Intestinal Inflammation.

Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.

Chiral perovskite-CdSe/ZnS QDs composites with high circularly polarized luminescence performance achieved through additive-solvent engineering.

Chiral perovskite materials are being extensively studied as one of the most promising candidates for circularly polarized luminescence (CPL)-related applications. Balancing chirality and photoluminescence (PL) properties is of great importance for enhancing the value of the dissymmetry factor (glum), and a higher glum value indicates better CPL. Chiral perovskite/quantum dot (QD) composites emerge as an effective strategy for overcoming the dilemma that achieving strong chirality and PL in chiral perovskite while at the same time achieving high glum in this composite is very crucial. Here, we choose diphenyl sulfoxide (DPSO) as an additive in the precursor solution of chiral perovskite to regulate the lattice distortion. How structural variation affects the chiral optoelectronic properties of the chiral perovskite has been further investigated. We find that chiral perovskite/CdSe-ZnS QD composites with strong CPL have been achieved, and the calculated maximum |glum| of the composites increased over one order of magnitude after solvent-additive modulation (1.55 × 10-3 for R-DMF/QDs, 1.58 × 10-2 for R-NMP-DPSO/QDs, -2.63 × 10-3 for S-DMF/QDs, and -2.65 × 10-2 for S-NMP-DPSO/QDs), even at room temperature. Our findings suggest that solvent-additive modulation can effectively regulate the lattice distortion of chiral perovskite, enhancing the value of glum for chiral perovskite/CdSe-ZnS QD composites.

Gut microbiome alterations during gastric cancer: evidence assessment of case-control studies.

Objectives: The study aims to systematically identify the alterations in gut microbiota that observed in gastric cancer through comprehensive assessment of case-control studies. Methods: The systematic literature search of PubMed, Embase, Cochrane Library, and Web of Science was conducted to identify case-control studies that compared the microbiomes of individuals with and without gastric cancer. Quality of included studies was evaluated with the Newcastle-Ottawa Quality Assessment Scale (NOS). Meta-analyses utilized a random-effects model, and subgroup and sensitivity analyses were performed to assess study heterogeneity. All data analyses were performed using the "metan" package in Stata 17.0, and the results were described using log odds ratios (log ORs) with 95% confidence intervals (CIs). Results: A total of 33 studies involving 4,829 participants were eligible for analysis with 29 studies provided changes in α diversity and 18 studies reported ß diversity. Meta-analysis showed that only the Shannon index demonstrated statistical significance for α-diversity [-5.078 (-9.470, -0.686)]. No significant differences were observed at the phylum level, while 11 bacteria at genus-level were identified significant changed, e.g., increasing in Lactobacillus [5.474, (0.949, 9.999)] and Streptococcus [5.095, (0.293, 9.897)] and decreasing in Porphyromonas and Rothia with the same [-8.602, (-11.396, -5.808)]. Sensitivity analysis indicated that the changes of 9 bacterial genus were robust. Subgroup analyses on countries revealed an increasing abundance of Helicobacter and Streptococcus in Koreans with gastric cancer, whereas those with gastric cancer from Portugal had a reduced Neisseria. Regarding the sample sources, the study observed an increase in Lactobacillus and Bacteroides in the gastric mucosa of people with gastric cancer, alongside Helicobacter and Streptococcus. However, the relative abundance of Bacteroides decreased compared to the non-gastric cancer group, which was indicated in fecal samples. Conclusion: This study identified robust changes of 9 bacterial genus in people with gastric cancer, which were country-/sample source-specific. Large-scale studies are needed to explore the mechanisms underlying these changes. Systematic Review: Unique Identifier: CRD42023437426 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023437426.

Effect of 18F-DCFPyL PET on changes in management of patients with prostate cancer: a systematic review and meta-analysis.

Purpose: Prostate-specific membrane antigen (PSMA)-targeted imaging has gained increasing interest in its application in prostate cancer lesion detection. Compared with 68Galium (68Ga), 18Fluoride (18F)-labeled imaging agent has easier syntheses, lower price, and a longer half-time. 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid positron emission tomography (18F-DCFPyL PET) has been recently approved by the U.S. Food and Drug Administration. Several studies have proven its superiority to conventional imaging techniques in detecting prostate cancer lesions. However, the impact of 18F-DCFPyL PET on the management of patients with prostate cancer is not well established. Thus, we performed a systematic review and meta-analysis of available data to evaluate the impact of 18F-DCFPyL PET on the management of patients with prostate cancer. Methods: The PubMed, Embase, Scopus, and Cochrane databases were searched up to April 2024. Studies that reported the proportion of changes in management after 18F-DCFPyL PET was performed in patients with prostate cancer were included. The Grading of Recommendations Assessment, Development, and Evaluation system was used for the quality evaluation of the included studies. The proportion of changes in management was pooled using a random effects model. Meta-regression analyses were performed to assess the potential correlation between the PET positivity and management changes. Results: Fourteen studies (3,078 patients with prostate cancer) were included in our review and analysis. The pooled percentage of management changes was 43.5% (95% confidence interval [CI]: 33-54%). In patients with biochemical recurrent and for primary staging, the pooled percentage was 50% (95% CI: 39-60%) and 22% (95% CI: 15-29%), respectively. In the meta-regression analyses, PET positivity was detected as a significant predictor of management change (p = 0.0023). Conclusion: 18F-DCFPyL PET significantly affects the management of patients with prostate cancer. Higher PET positivity rate significantly correlated with a higher proportion of management changes in patients with prostate cancer. However, more studies are still needed to confirm the important role of 18F-DCFPyL PET in the management of prostate cancer. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, CRD42022339178.

Clinical significance of downregulated NISCH expression in skin cutaneous melanoma: Modulation of tumor cell invasion, migration, and EMT via PAK1 inhibition.

OBJECTIVE: This study aimed to investigate the expression and functional role of NISCH in skin cutaneous melanoma (SKCM), exploring its association with clinical characteristics and its potential impact on human skin melanoma cell behavior. METHODS: The research assessed differential NISCH expression in SKCM tissues using the GEPIA (Gene Expression Profiling Interactive Analysis) database and validated these findings through immunohistochemical staining of 45 clinical samples. To affirm NISCH expression at the cellular level, three human skin melanoma cell lines (RPMI-7951, A375, MEL-5), and the human normal skin cell line HEMa underwent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Transwell experiments evaluated the migration and invasion capabilities of RPMI-7951 and A375 cells post-transduction with NISCH or PAK1 lentiviral activation particles. Additionally, qRT-PCR analysis of epithelial-mesenchymal transition (EMT)-related gene expression (Vimentin, E-cadherin, N-cadherin) was conducted in A375 and RPMI-7951 cells. RESULTS: SKCM tissues exhibited significantly reduced NISCH expression compared to normal tissues. Immunohistochemical analysis revealed predominant nuclear localization of NISCH in melanoma cells, with reduced expression significantly correlating with sex, advanced stage, and lymph node metastasis. Melanoma cell lines displayed lower NISCH expression levels compared to normal skin cells. Functional experiments showcased that NISCH overexpression suppressed p-PAK1/PAK1, while PAK1 upregulation notably increased melanoma cell migration, invasion, and induced EMT. Remarkably, NISCH overexpression counteracted PAK1-induced effects on EMT, migration, and invasion in melanoma cells. CONCLUSION: NISCH may significantly influence the aggressive behavior of SKCM cells via the PAK1 pathway, making it a potential therapeutic target for managing melanoma metastasis.

Applications and characterization of anti-browning enzymatically modified potato starch (EPS) film associated with chitosan (CTS)/L-Cys/citric acid (CA) on fresh-cut potato slices.

This study explores the influence of incorporating L-cysteine (L-Cys), chitosan (CTS), and citric acid (CA) on the enzymatic modification of potato starch (EPS) films to enhance anti-browning properties. Four types of EPS composite films were evaluated for preserving fresh-cut potato slices at low temperatures to inhibit browning. Their thermal, physiochemical, mechanical, and digestibility properties were assessed. Results indicate that the addition of CTS, CA, and L-Cys improved the anti-browning activity of the EPS films by increasing film thickness and reducing water vapor permeability (WVP), oxygen transmission rate (OTR), ultraviolet (UV) transmittance, and tensile strength (TS). Furthermore, these additives improved the film's microstructure, resulting in reinforced intermolecular interactions, increased elongation at break, heightened crystallinity, enhanced thermal stability, and favorable gastrointestinal digestibility. Overall, EPS/CTS/L-Cys/CA composite films show promise as edible packaging materials with effective anti-browning properties.

Citations of microRNA Biomarker Articles That Were Retracted: A Systematic Review.

Importance: Retraction is a tool that journals can use to deter research misconduct and alert their audience to erroneous content published in the journals. However, retracted articles may continue to damage science if they are still cited as legitimate articles. Objective: To characterize patterns of postretraction citations, particularly in microRNA biomarker research, a field with one of the highest rates of retraction. Evidence Review: Retracted scientific articles on microRNAs were retrieved from PubMed, Web of Science, and Retraction Watch between database inception and July 17, 2021, according to preestablished search strategies. Control articles with characteristics in common with retracted articles (ie, published in the same journals in the same years and months and with the same number of authors) were matched and retrieved from PubMed. Citation metrics of retractions and control articles were collected from Web of Science. PubPeer was referenced to examine the public response or comments on included retractions. Data were analyzed from September 2021 through March 2023. Findings: A total of 10 461 articles were analyzed, with 887 retractions and 9574 articles as controls. Among retracted articles, which were published from 1999 to 2021, there were 756 articles (85.23%) written by researchers affiliated with Chinese institutions. Retracted articles were cited 6327 times after retraction. Of 792 retracted articles that were cited, 621 articles (78.41%) were cited at least once after retraction and 238 articles (30.05%) were cited more often after retraction than before retraction. Overall citations (comprising citations before and after retraction) and postretraction citations accumulated over time (eg, the median [IQR] number of postretraction citations was 1 [1-2] and 23 [9-44] citations at the first 6 and 66 months, respectively, between retraction and citation retrieval). A random sample of 87 retracted articles (9.81%) recorded 478 citations after retraction, with 208 citations (43.51%) in articles published 12 months or longer after retraction. Of these citing articles, 19 articles (3.97%) mentioned the retractions. Compared with the control group of 1620 nonretracted articles, no significant differences were found in overall number of citations or citations after retraction. Among 478 articles citing retracted articles, 414 articles were found on PubMed and had matched control articles; these articles had higher odds of being subsequently retracted than 7954 matched control articles (odds ratio, 6.57; 95% CI, 3.39-12.72). Conclusions and Relevance: In this study, retraction was not associated with a reduction in citations of retracted articles, but articles that cited retracted publications had higher odds of later retraction. These findings suggest that journals may need to implement mechanisms for detection of postretraction citations.

Endothelial LAT1 (SLC7A5) Mediates S-Nitrosothiol Import and Modulates Respiratory Sequelae of Red Blood Cell Transfusion In Vivo.

BACKGROUND: Increased adhesivity of red blood cells (RBCs) to endothelial cells (ECs) may contribute to organ dysfunction in malaria, sickle cell disease, and diabetes. RBCs normally export nitric oxide (NO)-derived vascular signals, facilitating blood flow. S-nitrosothiols (SNOs) are thiol adducts formed in RBCs from precursor NO upon the oxygenation-linked allosteric transition in hemoglobin. RBCs export these vasoregulatory SNOs on demand, thereby regulating regional blood flow and preventing RBC-EC adhesion, and the large (system L) neutral amino acid transporter 1 (LAT1; SLC7A5) appears to mediate SNO export by RBCs. METHODS: To determine the role of LAT1-mediated SNO import by ECs generally and of LAT1-mediated SNO import by ECs in RBC SNO-dependent modulation of RBC sequestration and blood oxygenation in vivo, we engineered LAT1fl/fl; Cdh5-Cre+ mice, in which the putative SNO transporter LAT1 can be inducibly depleted (knocked down, KD) specifically in ECs ("LAT1ECKD"). RESULTS: We show that LAT1 in mouse lung ECs mediates cellular SNO uptake. ECs from LAT1ECKD mice (tamoxifen-induced LAT1fl/fl; Cdh5-Cre+) import SNOs poorly ex vivo compared with ECs from wild-type (tamoxifen-treated LAT1fl/fl; Cdh5-Cre-) mice. In vivo, endothelial depletion of LAT1 increased RBC sequestration in the lung and decreased blood oxygenation after RBC transfusion. CONCLUSION: This is the first study showing a role for SNO transport by LAT1 in ECs in a genetic mouse model. We provide the first direct evidence for the coordination of RBC SNO export with EC SNO import via LAT1. SNO flux via LAT1 modulates RBC-EC sequestration in lungs after transfusion, and its disruption impairs blood oxygenation by the lung.