Correlation between anesthetic concentration and low Apgar scores in neonates born via Cesarean sections under general anesthesia.

OBJECTIVES: This study aimed to compare plasma concentrations of anesthetic drugs administered during Cesarean section with low Apgar score in neonates deliveried under general anesthesia and analyze associated risk factors. METHODS: Data from 76 neonates undergoing Cesarean section under general anesthesia with blood concentrations of anesthetic drugs were analyzed. A low Apgar score was defined as ≤ 7. Perioperative maternal and neonatal data were collected and analyzed. Neonates were divided into a control group (Group CON, n = 65) and a low Apgar score group (Group LAS, n = 11) based on Apgar score. RESULTS: There were no significant differences in the plasma concentrations of anesthetic drugs in maternal artery, umbilical vein or umbilical artery blood between the two groups. Risk factors for neonatal low Apgar scores during Cesarean section under general anesthesia were premature delivery (aOR 10.2, 95% CI = 1.8-56.9) and preoperative fetal distress (aOR 9.6, 95% CI = 1.3-69.0). The prediction model was: probability = 1/(e­Y), Y= -4.607 + 2.318× (premature delivery) + 2.261× (fetal distress) (yes = 1, no = 0). The Hosmer-Lemeshow test showed χ²= 9.587, P = 0.213, and the area under the curve (AUC) was 0.850 (0.670 ~ 1.000). With a cutoff value of 0.695, sensitivity and specificity were 81.8% and 87.7%, respectively. CONCLUSIONS: There was no correlation between blood concentration of general anesthetic drugs and Apgar score or occurrence of neonatal low Apgar scores. Premature delivery and preoperative fetal distress were identified as independent risk factors for neonatal low Apgar scores after Cesarean section under general anesthesia.

Decoding the origins, spread, and global risks of mcr-9 gene.

BACKGROUND: The global spread of the plasmid-mediated mcr (mobilized colistin resistance) gene family presents a significant threat to the efficacy of colistin, a last-line defense against numerous Gram-negative pathogens. The mcr-9 is the second most prevalent variant after mcr-1. METHODS: A dataset of 698 mcr-9-positive isolates from 44 countries is compiled. The historical trajectory of the mcr-9 gene is reconstructed using Bayesian analysis. The effective reproduction number is used innovatively to study the transmission dynamics of this mobile-drug-resistant gene. FINDINGS: Our investigation traces the origins of mcr-9 back to the 1960s, revealing a subsequent expansion from Western Europe to the America and East Asia in the late 20th century. Currently, its transmissibility remains high in Western Europe. Intriguingly, mcr-9 likely emerged from human-associated Salmonella and exhibits a unique propensity for transmission within the Enterobacter. Our research provides a new perspective that this host preference may be driven by codon usage biases in plasmids. Specifically, mcr-9-carrying plasmids prefer the nucleotide C over T compared to mcr-1-carrying plasmids among synonymous codons. The same bias is seen in Enterobacter compared to Escherichia (respectively as their most dominant genus). Furthermore, we uncovered fascinating patterns of coexistence between different mcr-9 subtypes and other resistance genes. Characterized by its low colistin resistance, mcr-9 has used this seemingly benign feature to silently circumnavigate the globe, evading conventional detection methods. However, colistin-resistant Enterobacter strains with high mcr-9 expression have emerged clinically, implying a strong risk of mcr-9 evolving into a global "true-resistance-gene". INTERPRETATION: This study explores the mcr-9 gene, emphasizing its origin, adaptability, and dissemination potential. Given the high mcr-9 expression colistin-resistant strains was observed in clinically the prevalence of mcr-9 poses a significant challenge to drug resistance prevention and control within the One Health framework. FUNDING: This work was partially supported by the National Natural Science Foundation of China (Grant No. 32141001 and 81991533).

Diagnostic Significance of Serum Long Noncoding HOX Antisense Intergenic Ribonucleic Acid in Patients with Hepatitis B Virus Related Hepatocellular Carcinoma.

BACKGROUND/AIMS:  Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the third leading cause of cancer-related mortality. Extensive literature suggests that long noncoding RNAs play a role in the progression of HCC and hold potential as diagnostic biomarkers for this disease. MATERIALS AND METHODS:  We examined the serum levels of HOX antisense intergenic RNA (HOTAIR) in 49 hepatitis patients, 31 liver cirrhosis (LC), and 37 HCC patients using quantitative real-time polymerase chain reaction. Correlations between serum HOTAIR levels and clinical data were evaluated in HCC patients. The receiver operating characteristic curve was utilized to analyze the diagnostic potency of HOTAIR. RESULTS:  The HOTAIR levels in serum were significantly higher in HCC patients compared to those with hepatitis (P = .003) and LC patients (P = .048). There was a significant association between the serum levels of HOTAIR and positivity of hepatitis B e antigen (HBeAg) (P = .039) as well as portal vein tumor thrombus (P = .040) in HCC patients. The area under the curve (AUC) for HOTAIR for distinguishing HCC from hepatitis and LC was 0.697. The combined AUC for HOTAIR, HBeAg, and alpha-fetoprotein (AFP) was 0.777. CONCLUSION:  Serum HOTAIR functions as a potential diagnostic marker for hepatitis B virus-related HCC. Combining HOTAIR with clinical data and AFP can reinforce the diagnostic precision on HCC.

CHRM3 (rs2165870) gene polymorphism is related to postoperative vomiting in female patients undergoing laparoscopic surgery. Prospective observational study.

BACKGROUND: Postoperative nausea and vomiting are common complications after surgery, and female patients are more likely to experience these adverse events. The goal of this study was to explore the relationship between the CHRM3 rs2165870 polymorphism and postoperative vomiting incidence in female patients who underwent laparoscopic surgery. METHODS: Two hundred female patients who underwent elective laparoscopic surgery with subsequent patient-controlled intravenous analgesia using dexmedetomidine and sufentanil were prospectively enrolled. The CHRM3 rs2165870 and KCNB2 rs349358 polymorphisms were genotyped using MassARRAY SNP typing technology. Demographic data and preoperative laboratory results of all patients were recorded. Postoperative analgesia-related information, incidence of postoperative nausea and vomiting, and other adverse events were followed up and recorded for analysis. RESULTS: No significant differences were observed in any of the demographic characteristics of these patients among the different genotype carriers (P>0.05). The percentages of patients with each genotype of CHRM3 were 67% (GG), 28.5% (GA) and 4.5% (AA). We found that the AA or A allele of the CHRM3 rs2165870 polymorphism elevated the risk of postoperative vomiting (AA versus GG; OR, 6.94; 95% CI, 1.49-32.46; P = 0.014; A versus G; OR, 2.52; 95% CI, 1.22-5.19; P = 0.012). The percentages of patients with each genotype of KCNB2 were 84.5% (TT), 15.5% (CT) and 0% (CC). There were no significant differences in the postoperative nausea or vomiting rate across the KCNB2 rs349358 polymorphisms (P>0.05). CONCLUSION: The CHRM3 rs2165870 polymorphism is associated with the occurrence of postoperative vomiting in female patients who have undergone laparoscopic surgery. The AA genotype or A allele of the CHRM3 rs2165870 polymorphism elevates the risk of postoperative vomiting. TRIAL REGISTRATION: www.chictr.org.cn, registration number: ChiCTR2200062425.

PathoTracker: an online analytical metagenomic platform for Klebsiella pneumoniae feature identification and outbreak alerting.

Clinical metagenomics (CMg) Nanopore sequencing can facilitate infectious disease diagnosis. In China, sub-lineages ST11-KL64 and ST11-KL47 Carbapenem-resistant Klebsiella pneumoniae (CRKP) are widely prevalent. We propose PathoTracker, a specially compiled database and arranged method for strain feature identification in CMg samples and CRKP traceability. A database targeting high-prevalence horizontal gene transfer in CRKP strains and a ST11-only database for distinguishing two sub-lineages in China were created. To make the database user-friendly, facilitate immediate downstream strain feature identification from raw Nanopore metagenomic data, and avoid the need for phylogenetic analysis from scratch, we developed data analysis methods. The methods included pre-performed phylogenetic analysis, gene-isolate-cluster index and multilevel pan-genome database and reduced storage space by 10-fold and random-access memory by 52-fold compared with normal methods. PathoTracker can provide accurate and fast strain-level analysis for CMg data after 1 h Nanopore sequencing, allowing early warning of outbreaks. A user-friendly page ( http://PathoTracker.pku.edu.cn/ ) was developed to facilitate online analysis, including strain-level feature, species identifications and phylogenetic analyses. PathoTracker proposed in this study will aid in the downstream analysis of CMg.

Study on rock fracture mechanism and hydraulic fracturing propagation law of heterogeneous tight sandstone reservoir.

Hydraulic fracturing technology is an effective way to develop tight sandstone reservoirs with low porosity and permeability. The tight sandstone reservoir is heterogeneous and the heterogeneity characteristics has an important influence on fracture propagation. To investigate hydraulic fracture performance in heterogeneous tight reservoir, the X-ray diffraction experiments are carried out, the Weibull distribution method and finite element method are applied to establish the uniaxial compression model and the hydraulic fracture propagation model of heterogeneous tight sandstone. Meanwhile, the sensitivity of different heterogeneity characterization factors and the multi-fracture propagation mechanism during hydraulic fracture propagation is analyzed. The results indicate that the pressure transfer in the heterogeneous reservoir is non-uniform, showing a multi-point initiation fracture mode. For different heterogeneity characterization factors, the heterogeneity characteristics based on elastic modulus are the most sensitive. The multi-fracture propagation of heterogeneous tight sandstone reservoir is different from that of homogeneous reservoir, the fracture propagation morphology is more complex. With the increase of stress difference, the fracture propagation length increases. With the increase of injection rate, the fracture propagation length increases. With the increase of cluster spacing, the propagation length of multiple fractures tends to propagate evenly. This study clarifies the influence of heterogeneity on fracture propagation and provides some guidance for fracturing optimization of tight sandstone reservoirs.

Type 2 herpes simplex virus-induced anti-N-methyl-D-aspartate receptor encephalitis responsive to immunoglobulin monotherapy.

Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated.

A Prognostic Model Incorporating Relevant Peripheral Blood Inflammation Indicator to Predict Postherpetic Neuralgia in Patients with Acute Herpes Zoster.

Objective: To determine the risk of postherpetic neuralgia (PHN) in patients with acute herpes zoster (HZ), this study developed and validated a novel clinical prediction model by incorporating a relevant peripheral blood inflammation indicator. Methods: Between January 2019 and June 2023, 209 patients with acute HZ were categorized into the PHN group (n = 62) and the non-PHN group (n = 147). Univariate and multivariate logistic regression analyses were conducted to identify risk factors serving as independent predictors of PHN development. Subsequently, a nomogram prediction model was established, and the discriminative ability and calibration were evaluated using the receiver operating characteristic curve, calibration plots, and decision curve analysis (DCA). The nomogram model was internally verified through the bootstrap test method. Results: According to univariate logistic regression analyses, five variables, namely age, hypertension, acute phase Numeric Rating Scale (NRS-11) score, platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index, were significantly associated with PHN development. Multifactorial analysis further unveiled that age (odds ratio (OR) [95% confidence interval (CI)]: 2.309 [1.163-4.660]), acute phase NRS-11 score (OR [95% CI]: 2.837 [1.294-6.275]), and PLR (OR [95% CI]: 1.015 [1.010-1.022]) were independent risk factors for PHN. These three predictors were integrated to establish the prediction model and construct the nomogram. The area under the receiver operating characteristic curve (AUC) for predicting the PHN risk was 0.787, and the AUC of internal validation determined using the bootstrap method was 0.776. The DCA and calibration curve also indicated that the predictive performance of the nomogram model was commendable. Conclusion: In this study, a risk prediction model was developed and validated to accurately forecast the probability of PHN after HZ, thereby demonstrating favorable discrimination, calibration, and clinical applicability.

Association of Methyl Donor Nutrients' Dietary Intake and Cognitive Impairment in the Elderly Based on the Intestinal Microbiome.

Globally, cognitive impairment (CI) is the leading cause of disability and dependency among the elderly, presenting a significant public health concern. However, there is currently a deficiency in pharmacological interventions that can effectively cure or significantly reverse the progression of cognitive impairment. Methyl donor nutrients (MDNs), including folic acid, choline, and vitamin B12, have been identified as potential enhancers of cognitive function. Nevertheless, there remains a dearth of comprehensive research investigating the connection between the dietary intake of MDNs and CI. In our study, we comprehensively assessed the relationship between MDNs' dietary intake and CI in older adults, utilizing 16S rRNA gene sequencing to investigate the potential underlying mechanisms. The results showed an obvious difference in the methyl-donor nutritional quality index (MNQI) between the dementia (D) group and the dementia-free (DF) group. Specifically, there was a lower MNQI in the D group than that in the DF group. For the gut microbiome, the beta diversity of gut flora exhibited higher levels in the high methyl-donor nutritional quality (HQ) group as opposed to the low methyl-donor nutritional quality (LQ) group, and lower levels in the D group in comparison to the DF group. Subsequently, we performed a correlation analysis to examine the relationship between the relative abundance of microbiota, the intake of MDNs, and Montreal Cognitive Assessment (MoCA) scores, ultimately identifying ten genera with potential regulatory functions. Additionally, KEGG pathway analyses suggested that the one-carbon metabolism, chronic inflammation, and DNA synthesis potentially serve as pathways through which MDNs may be promising for influencing cognitive function. These results implied that MDNs might have the potential to enhance cognitive function through the regulation of microbiota homeostasis. This study offers dietary recommendations for the prevention and management of CI in the elderly.

Impact of diabetic kidney disease on post-operative complications after primary elective total hip arthroplasty: a nationwide database analysis.

BACKGROUND: The high prevalence of diabetic kidney disease (DKD) in the United States necessitates further investigation into its impact on complications associated with total hip arthroplasty (THA). This study utilizes a large nationwide database to explore risk factors in DKD cases undergoing THA. METHODS: This research utilized a case-control design, leveraging data from the national inpatient sample for the years 2016 to 2019. Employing propensity score matching (PSM), patients diagnosed with DKD were paired on a 1:1 basis with individuals free of DKD, ensuring equivalent age, sex, race, Elixhauser Comorbidity Index (ECI), and insurance coverage. Subsequently, comparisons were drawn between these PSM-matched cohorts, examining their characteristics and the incidence of post-THA complications. Multivariate logistic regression analysis was then employed to evaluate the risk of early complications after surgery. RESULTS: DKD's prevalence in the THA cohort was 2.38%. A 7-year age gap separated DKD and non-DKD patients (74 vs. 67 years, P < 0.0001). Additionally, individuals aged above 75 exhibited a substantial 22.58% increase in DKD risk (49.16% vs. 26.58%, P < 0.0001). Notably, linear regression analysis yielded a significant association between DKD and postoperative acute kidney injury (AKI), with DKD patients demonstrating 2.274-fold greater odds of AKI in contrast with non-DKD individuals (95% CI: 2.091-2.473). CONCLUSIONS: This study demonstrates that DKD is a significant risk factor for AKI in patients undergoing total hip arthroplasty. Optimizing preoperative kidney function through appropriate interventions might decrease the risk of poor prognosis in this population. More prospective research is warranted to investigate the potential of targeted kidney function improvement strategies in reducing AKI rates after THA. The findings of this study hold promise for enhancing preoperative counseling by surgeons, enabling them to provide DKD patients undergoing THA with more precise information regarding the risks associated with their condition.

FANCI Inhibition Induces PARP1 Redistribution to Enhance the Efficacy of PARP Inhibitors in Breast Cancer.

Breast cancer is a global public health concern with high mortality rates, necessitating the development of innovative treatment strategies. PARP inhibitors have shown efficacy in certain patient populations, but their application is largely limited to cancers with homologous recombination deficiency. Here, we identified the suppression of FANCI as a therapeutic strategy to enhance the efficacy of PARP inhibitors in breast cancer. Elevated FANCI expression in breast cancer was associated with poor prognosis and increased cell proliferation and migration. FANCI interacted with PARP1, and suppressing FANCI limited the nuclear localization and functionality of PARP1. Importantly, FANCI inhibition sensitized breast cancer cells to the PARP inhibitor talazoparib in the absence of BRCA mutations. Additionally, the CDK4/6 inhibitor palbociclib enhanced the sensitivity of breast cancer cells to talazoparib through FANCI inhibition. These findings highlight the potential of targeting FANCI to enhance the efficacy of PARP inhibitors in treating breast cancer.

Study on the Mass Spectrometry Cleavage Pattern of Quinolone Antibiotics.

RATIONALE: Quinolone antibiotics are extensively used clinically for human treatment and in agriculture. However, improper and excessive use can lead to the persistence of quinolone residues in animal tissues, potentially accumulating in the human body and posing health risks. Investigating the correlation between mass spectrometry cleavage patterns and molecular structural features enhances the analytical framework for detecting trace or unknown impurities in quinolones. METHODS: To collect data, we employed triple quadrupole linear ion trap mass spectrometry in electrospray positive ion mode. Primary mass spectrometry scanning was utilized to confirm parent ions, while secondary mass spectrometry scanning enabled the observation of fragment ions. The cleavage characteristics and pathways of the compounds were inferred from accurate mass-to-charge ratios obtained from both primary and secondary mass spectrometry. RESULTS: Under soft ionization conditions, the compounds generally exhibited characteristic fragment ions of [M+H-H2O]+, [M+H-CO]+, and [M+H-H2O-CO]+. Additionally, subtle variations were observed in each compound due to differences in modifying groups. For instance, upon deacidification, the piperazine ring structure underwent breakage and rearrangement, yielding fragment ion peaks devoid of neutral molecules such as C2H5N, C3H7N, or C4H8N. Notably, compounds featuring a cyclopropyl substituent group at the N-1 position typically exhibited characteristic fragments resulting from the loss of the cyclopropyl radical (⋅C3H5). Moreover, substituents at the N-1 and C-8 positions, when linked to form a six-membered carbocyclic ring, were prone to cleavage, releasing the neutral C3H6 molecule. CONCLUSION: Quinolone antibiotics share structural similarities in their parent nuclei, leading to partially similar cleavage pathways. Nevertheless, distinct cleavage patterns emerge due to variations in functional groups. According to the difference of mass spectrometry cleavage patterns, it can provide an identification basis for the measured detection of antibiotics.

Tracking intra-species and inter-genus transmission of KPC through global plasmids mining.

Klebsiella pneumoniae carbapenemase (KPC) poses a major public health risk. Understanding its transmission dynamics requires examining the epidemiological features of related plasmids. Our study compiled 15,660 blaKPC-positive isolates globally over the past two decades. We found extensive diversity in the genetic background of KPC, with 23 Tn4401-related and 341 non-Tn4401 variants across 163 plasmid types in 14 genera. Intra-K. pneumoniae and cross-genus KPC transmission patterns varied across four distinct periods. In the initial periods, plasmids with narrow host ranges gradually established a survival advantage. In later periods, broad-host-range plasmids became crucial for cross-genera transmission. In total, 61 intra-K. pneumoniae and 66 cross-genus transmission units have been detected. Furthermore, phylogenetic reconstruction dated the origin of KPC transmission back to 1991 and revealed frequent exchanges across countries. Our research highlights the frequent and transient spread events of KPC mediated by plasmids across multiple genera and offers theoretical support for high-risk plasmid monitoring.

Association of methyl donor nutrients dietary intake and sleep disorders in the elderly revealed by the intestinal microbiome.

Currently, sleep disorders (SD) in the elderly are gaining prominence globally and are becoming a significant public health concern. Methyl donor nutrients (MDNs), such as vitamin B6, vitamin B12, folate, and choline, have been reported to have the potential to improve sleep disorders. Moreover, MDNs help to maintain gut flora homeostasis, and are closely associated with the development of SD. Nevertheless, there has been a lack of comprehensive human studies examining the association between MDNs intake and SD. In our study, we comprehensively evaluated the association between MDNs intake and SD in the elderly and used 16S rRNA gene sequencing to explore the underlying mechanism. We found that the SD group (n = 91) had a lower methyl-donor nutritional quality index (MNQI) and a trend toward lower intake compared to the control group (n = 147). Based on the intestinal microbiome, the beta diversity of the intestinal flora was higher in the high methyl-donor nutritional quality (HQ) group compared to the low methyl-donor nutritional quality (LQ) group, and it was lower in the SD group compared to the control group. This suggests that MDNs may regulate sleep by modulating the abundance distribution of the microbiota. Subsequently, we performed correlation analyses between the relative abundance of the microbiota, MDNs intake, and the Pittsburgh Sleep Quality Index (PSQI), identifying five genera with potential regulatory roles. The KEGG pathway analysis indicated that energy metabolism and one-carbon metabolism might be the pathways through which MDNs modulate sleep. This study offers dietary guidance strategies for managing SD in the elderly and provides insights for targeted microbiota intervention.

Photo-Assisted Rechargeable Metal Batteries: Principles, Progress, and Perspectives.

The utilization of diverse energy storage devices is imperative in the contemporary society. Taking advantage of solar power, a significant environmentally friendly and sustainable energy resource, holds great appeal for future storage of energy because it can solve the dilemma of fossil energy depletion and the resulting environmental problems once and for all. Recently, photo-assisted energy storage devices, especially photo-assisted rechargeable metal batteries, are rapidly developed owing to the ability to efficiently convert and store solar energy and the simple configuration, as well as the fact that conventional Li/Zn-ion batteries are widely commercialized. Considering many puzzles arising from the rapid development of photo-assisted rechargeable metal batteries, this review commences by introducing the fundamental concepts of batteries and photo-electrochemistry, followed by an exploration of the current advancements in photo-assisted rechargeable metal batteries. Specifically, it delves into the elucidation of device components, operating principles, types, and practical applications. Furthermore, this paper categorizes, specifies, and summarizes several detailed examples of photo-assisted energy storage devices. Lastly, it addresses the challenges and bottlenecks faced by these energy storage systems while providing future perspectives to facilitate their transition from laboratory research to industrial implementation.

Targeting Aging and Longevity with Exogenous Nucleotides (TALENTs): Rationale, Design, and Baseline Characteristics from a Randomized Controlled Trial in Older Adults.

Nucleotides (NTs), important biomolecules involved in numerous cellular processes, have been proposed as potential candidates for anti-aging interventions. However, whether nucleotides can act as an anti-aging supplement in older adults remains unclear. TALENTs is a randomized, double-blinded, placebo-controlled trial that evaluates the efficacy and safety of NTs as an anti-aging supplement in older adults by exploring the effects of NTs on multiple dimensions of aging in a rigorous scientific setting. Eligible community-dwelling adults aged 60-70 years were randomly assigned equally to two groups: nucleotides intervention group and placebo control group. Comprehensive geriatric health assessments were performed at baseline, 2-months, and 4-months of the intervention. Biological specimens were collected and stored for age-related biomarker testing and multi-omics sequencing. The primary outcome was the change from baseline to 4 months on leukocyte telomere length and DNA methylation age. The secondary aims were the changes in possible mechanisms underlying aging processes (immunity, inflammatory profile, oxidative stress, gene stability, endocrine, metabolism, and cardiovascular function). Other outcomes were changes in physical function, body composition and geriatric health assessment (including sleep quality, cognitive function, fatigue, frailty, and psychology). In the RCT, 301 participants were assessed for eligibility and 122 were enrolled. Participants averaged 65.65 years of age, and were predominately female (67.21%). All baseline characteristics were well-balanced between groups, as expected due to randomization. The majority of participants were pre-frailty and had at least one chronic condition. The mean scores for physical activity, psychological, fatigue and quality of life were within the normal range. However, nearly half of the participants still had room for improvement in cognitive level and sleep quality. This TALENTs trial will represent one of the most comprehensive experimental clinical trials in which supplements are administered to elderly participants. The findings of this study will contribute to our understanding of the anti-aging effects of NTs and provide insights into their potential applications in geriatric healthcare.

Visible Light-Gating Responsive Nanochannel for Controlled Release of the Fungicide.

Fungicides have been widely used to protect crops from the disease of pythium aphanidermatum (PA). However, excessive use of synthetic fungicides can lead to fungal pathogens developing microbicide resistance. Recently, biomimetic nano-delivery systems have been used for controlled release, reducing the overuse of fungicides, and thereby protecting the environment. In this paper, inspired by chloroplast membranes, visible light biomimetic channels are constructed by using retinal, the main component of green pigment on chloroplasts in plants, which can achieve the precise controlled release of the model fungicide methylene blue (MB). The experimental results show that the biomimetic channels have good circularity after and before light conditions. In addition, it is also found that the release of MB in visible light by the retinal-modified channels is 8.78 µmol·m-2·h-1, which is four times higher than that in the before light conditions. Furthermore, MB, a bactericide drug model released under visible light, can effectively inhibit the growth of PA, reaching a 97% inhibition effect. The biomimetic nanochannels can realize the controlled release of the fungicide MB, which provides a new way for the treatment of PA on the leaves surface of cucumber, further expanding the application field of biomimetic nanomembrane carrier materials.

A comprehensive review on hemocyanin from marine products: Structure, functions, its implications for the food industry and beyond.

Hemocyanin, an oxygen-transport protein, is widely distributed in the hemolymph of marine arthropods and mollusks, playing an important role in their physiological processes. Recently, hemocyanin has been recognized as a multifunctional glycoprotein involved in the immunological responses of aquatic invertebrates. Consequently, the link between hemocyanin functions and their potential applications has garnered increased attention. This review offers an integrated overview of hemocyanin's structure, physicochemical characteristics, and bioactivities to further promote the utilization of hemocyanin derived from marine products. Specifically, we review its implication in two aspects of food and aquaculture industries: quality and health. Hemocyanin's inducible phenoloxidase activity is thought to be an inducer of melanosis in crustaceans. New anti-melanosis agents targeted to hemocyanin need to be explored. The red-color change observed in shrimp shells is related to hemocyanin, affecting consumer preferences. Hemocyanin's adaptive modification in response to the aquatic environment is available as a biomarker. Additionally, hemocyanin is endowed with bioactivities encompassing anti-microbial, antiviral, and therapeutic activities. Hemocyanin is also a novel allergen and its allergenic features remain incompletely characterized.

Dynamic genomic changes in methotrexate-resistant human cancer cell lines beyond DHFR amplification suggest potential new targets for preventing drug resistance.

BACKGROUND: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. METHODS: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. RESULTS: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. CONCLUSION: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies.

Pseudorabies virus manipulates mitochondrial tryptophanyl-tRNA synthetase 2 for viral replication.

The pseudorabies virus (PRV) is identified as a double-helical DNA virus responsible for causing Aujeszky's disease, which results in considerable economic impacts globally. The enzyme tryptophanyl-tRNA synthetase 2 (WARS2), a mitochondrial protein involved in protein synthesis, is recognized for its broad expression and vital role in the translation process. The findings of our study showed an increase in both mRNA and protein levels of WARS2 following PRV infection in both cell cultures and animal models. Suppressing WARS2 expression via RNA interference in PK-15 â€‹cells led to a reduction in PRV infection rates, whereas enhancing WARS2 expression resulted in increased infection rates. Furthermore, the activation of WARS2 in response to PRV was found to be reliant on the cGAS/STING/TBK1/IRF3 signaling pathway and the interferon-alpha receptor-1, highlighting its regulation via the type I interferon signaling pathway. Further analysis revealed that reducing WARS2 levels hindered PRV's ability to promote protein and lipid synthesis. Our research provides novel evidence that WARS2 facilitates PRV infection through its management of protein and lipid levels, presenting new avenues for developing preventative and therapeutic measures against PRV infections.