Structure-guided design of novel biphenyl-quinazoline derivatives as potent non-nucleoside reverse transcriptase inhibitors featuring improved anti-resistance, selectivity, and solubility.

In pursuit of enhancing the anti-resistance efficacy and solubility of our previously identified NNRTI 1, a series of biphenyl-quinazoline derivatives were synthesized employing a structure-based drug design strategy. Noteworthy advancements in anti-resistance efficacy were discerned among some of these analogs, prominently exemplified by compound 7ag, which exhibited a remarkable 1.37 to 602.41-fold increase in potency against mutant strains (Y181C, L100I, Y188L, F227L + V106A, and K103N + Y181C) in comparison to compound 1. Compound 7ag also demonstrated comparable anti-HIV activity against both WT HIV and K103N, albeit with a marginal reduction in activity against E138K. Of significance, this analog showed augmented selectivity index (SI > 5368) relative to compound 1 (SI > 37764), Nevirapine (SI > 158), Efavirenz (SI > 269), and Etravirine (SI > 1519). Moreover, it displayed a significant enhancement in water solubility, surpassing that of compound 1, Etravirine, and Rilpivirine. To elucidate the underlying molecular mechanisms, molecular docking studies were undertaken to probe the critical interactions between 7ag and both WT and mutant strains of HIV-1 RT. These findings furnish invaluable insights driving further advancements in the development of DAPYs for HIV therapy.

Efficacy of Random Forest Models in Predicting Multidrug-Resistant Gram-Negative Bacterial Nosocomial Infections Compared to Traditional Logistic Regression Models.

This study evaluates whether random forest (RF) models are as effective as traditional Logistic Regression (LR) models in predicting multidrug-resistant Gram-negative bacterial nosocomial infections. Data were collected from 541 patients with hospital-acquired Gram-negative bacterial infections at two tertiary-level hospitals in Urumqi, Xinjiang, China, from August 2022 to November 2023. Relevant literature informed the selection of significant predictors based on patients' pre-infection clinical information and medication history. The data were split into a training set of 379 cases and a validation set of 162 cases, adhering to a 7:3 ratio. Both RF and LR models were developed using the training set and subsequently evaluated on the validation set. The LR model achieved an accuracy of 84.57%, sensitivity of 82.89%, specificity of 80.10%, positive predictive value of 84%, negative predictive value of 85.06%, and a Yoden index of 0.69. In contrast, the RF model demonstrated superior performance with an accuracy of 89.51%, sensitivity of 90.79%, specificity of 88.37%, positive predictive value of 87.34%, negative predictive value of 91.57%, and a Yoden index of 0.79. Receiver operating characteristic curve analysis revealed an area under the curve of 0.91 for the LR model and 0.94 for the RF model. These findings indicate that the RF model surpasses the LR model in specificity, sensitivity, and accuracy in predicting hospital-acquired multidrug-resistant Gram-negative infections, showcasing its greater potential for clinical application.

Subgenome-aware analyses reveal the genomic consequences of ancient allopolyploid hybridizations throughout the cotton family.

Malvaceae comprise some 4,225 species in 243 genera and nine subfamilies and include economically important species, such as cacao, cotton, durian, and jute, with cotton an important model system for studying the domestication of polyploids. Here, we use chromosome-level genome assemblies from representatives of five or six subfamilies (depending on the placement of Ochroma) to differentiate coexisting subgenomes and their evolution during the family's deep history. The results reveal that the allohexaploid Helicteroideae partially derive from an allotetraploid Sterculioideae and also form a component of the allodecaploid Bombacoideae and Malvoideae. The ancestral Malvaceae karyotype consists of 11 protochromosomes. Four subfamilies share a unique reciprocal chromosome translocation, and two other subfamilies share a chromosome fusion. DNA alignments of single-copy nuclear genes do not yield the same relationships as inferred from chromosome structural traits, probably because of genes originating from different ancestral subgenomes. These results illustrate how chromosome-structural data can unravel the evolutionary history of groups with ancient hybrid genomes.

Inhibitory Effect of Acetaminophen on Ocular Pigmentation and its Relationship with Thyroxine in Zebrafish Embryos.

Acetaminophen (N-acetyl-p-aminophenol; APAP) is one of the most widely used analgesics. To examine the toxicity of APAP, we used zebrafish embryos as model animals to detect the effect of APAP on the thyroid system of zebrafish embryos. The zebrafish embryos were exposed to APAP from 4 h post fertilization (4 hpf) until observation. The experimental results showed that APAP caused pericardial edema and decreased pigmentation in the zebrafish embryos or larvae. The APAP treatment caused a decrease in the expression of tpo and thrß in the zebrafish at 36 and 72 hpf. The transcriptomic analysis found that APAP affected retinol metabolism, the metabolism of xenobiotics by cytochrome P450, and the tyrosine metabolism pathway. The harmful effect of APAP on zebrafish embryos might be due to its disrupting effect on the functional regulation of the thyroid hormone system.

Ubiquitination and deubiquitination in the regulation of N6-methyladenosine functional molecules.

N6 methyladenosine (m6A) is the most prevalent RNA epigenetic modification, regulated by methyltransferases and demethyltransferases and recognized by methylation-related reading proteins to impact mRNA splicing, translocation, stability, and translation efficiency. It significantly affects a variety of activities, including stem cell maintenance and differentiation, tumor formation, immune regulation, and metabolic disorders. Ubiquitination refers to the specific modification of target proteins by ubiquitin molecule in response to a series of enzymes. E3 ligases connect ubiquitin to target proteins and usually lead to protein degradation. On the contrary, deubiquitination induced by deubiquitinating enzymes (DUBs) can separate ubiquitin and regulate the stability of protein. Recent studies have emphasized the potential importance of ubiquitination and deubiquitination in controlling the function of m6A modification. In this review, we discuss the impact of ubiquitination and deubiquitination on m6A functional molecules in diseases, such as metabolism, cellular stress, and tumor growth.

Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia.

Human endogenous retroviruses (HERVs) are remnants of retroviral infections in human germline cells from millions of years ago. Among these, ERVW-1 (also known as HERV-W-ENV, ERVWE1, or ENVW) encodes the envelope protein of the HERV-W family, which contributes to the pathophysiology of schizophrenia. Additionally, neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with schizophrenia. Here, our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset (GSE53987) were mainly related to ferroptosis and its associated pathways. Clinical data demonstrated significantly lower expression levels of ferroptosis-related genes, particularly Glutathione peroxidase 4 (GPX4) and solute carrier family 3 member 2 (SLC3A2), in schizophrenia patients compared to normal controls. Further in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in schizophrenia. Studies indicated that ERVW-1 increased iron levels, malondialdehyde (MDA), and transferrin receptor protein 1 (TFR1) expression while decreasing glutathione (GSH) levels and triggering the loss of mitochondrial membrane potential, suggesting that ERVW-1 can induce ferroptosis. Ongoing research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter activities. Moreover, Ferrostatin-1 (Fer-1), the ferroptosis inhibitor, reversed the iron accumulation and mitochondrial membrane potential loss, as well as restored the expressions of ferroptosis markers GSH, MDA, and TFR1 induced by ERVW-1. In conclusion, ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2, revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.

Captive ERVWE1 triggers impairment of 5-HT neuronal plasticity in the first-episode schizophrenia by post-transcriptional activation of HTR1B in ALKBH5-m6A dependent epigenetic mechanisms.

BACKGROUND: Abnormalities in the 5-HT system and synaptic plasticity are hallmark features of schizophrenia. Previous studies suggest that the human endogenous retrovirus W family envelope (ERVWE1) is an influential risk factor for schizophrenia and inversely correlates with 5-HT4 receptor in schizophrenia. To our knowledge, no data describes the effect of ERVWE1 on 5-HT neuronal plasticity. N6-methyladenosine (m6A) regulates gene expression and impacts synaptic plasticity. Our research aims to systematically investigate the effects of ERVWE1 on 5-HT neuronal plasticity through m6A modification in schizophrenia. RESULTS: HTR1B, ALKBH5, and Arc exhibited higher levels in individuals with first-episode schizophrenia compared to the controls and showed a strong positive correlation with ERVWE1. Interestingly, HTR1B was also correlated with ALKBH5 and Arc. Further analyses confirmed that ALKBH5 may be an independent risk factor for schizophrenia. In vitro studies, we discovered that ERVWE1 enhanced HTR1B expression, thereby activating the ERK-ELK1-Arc pathway and reducing the complexity and spine density of 5-HT neurons. Furthermore, ERVWE1 reduced m6A levels through ALKBH5 demethylation. ERVWE1 induced HTR1B upregulation by improving its mRNA stability in ALKBH5-m6A-dependent epigenetic mechanisms. Importantly, ALKBH5 mediated the observed alterations in 5-HT neuronal plasticity induced by ERVWE1. CONCLUSIONS: Overall, HTR1B, Arc, and ALKBH5 levels were increased in schizophrenia and positively associated with ERVWE1. Moreover, ALKBH5 was a novel risk gene for schizophrenia. ERVWE1 impaired 5-HT neuronal plasticity in ALKBH5-m6A dependent mechanism by the HTR1B-ERK-ELK1-Arc pathway, which may be an important contributor to aberrant synaptic plasticity in schizophrenia.

Limited energy migration and circumscribed multiphonon relaxation produced non-concentration quenching in a novel dazzling red-emitting phosphor.

White LED applications are still constrained by extremely efficient narrow band red emitting phosphors. Meanwhile, the concentration quenching induced by energy migration is the main reason that limits the emission intensity of a red emitting phosphor. Therefore, developing a novel red emitting material with energy migration limitations seems necessary. Here, we proposed and realized the non-concentration quenching doping of Eu3+ ions in a Sr9Y2-2xW4O24:xEu3+ (0 ≤ x ≤ 1.0) phosphor for the first time by means of host preferential selection. By clearly investigating the crystal structure and luminescence kinetics, the long-distance between the nearby Eu3+ ions and the low phonon energy are the main reasons that suppress the energy migration and the cross-relaxation among Eu3+ ions. These advantages result in a high internal (90.47%) and external quantum efficiency (42.1%) of Sr9Eu2W4O24. With the help of the Judd-Ofelt theory and the large value of oscillator strength Ω2, Eu3+ ions are verified to occupy the non-symmetric lattice site with high color purity (94.4%). In addition, only 5.2% emission intensity loss at 140 °C can guarantee its application in LED devices. Moreover, the SYWO:Eu3+ phosphor has high thermal tolerance, high color stability, excellent moisture resistance and superior physical/chemical stability, and thus has broad practical spectral application prospects. The prepared WLED shows superior performance, and the calculated NTSC values are as high as 101.8% and 104.7%, respectively. For comparison, the optical performances of the Sr9Y2W4O24:Eu3+ phosphor outperform those of the standard commercial red phosphors, Y2O3:Eu3+ and Y2O2S:Eu3+, and almost match that of K2MnF6. These results may pave the way for fresh approaches to the study of high-performance Eu3+-activated phosphors.

Safety and immunogenicity of the COVID-19 mRNA vaccine CS-2034: A randomized, double-blind, dose-exploration, placebo-controlled multicenter Phase I clinical trial in healthy Chinese adults.

BACKGROUND: The novel coronavirus pneumonia (COVID-19) is an infectious disease caused by the infection of a novel coronavirus known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has resulted in millions of deaths. We aimed to evaluate the safety and immunogenicity of the COVID-19 mRNA vaccine (CS-2034, CanSino, Shanghai, China) in adults without COVID-19 infection from China. METHOD: This is a multicenter Phase I clinical trial with a randomized, double-blinded, dose-exploration, placebo-controlled design. The trial recruited 40 seronegative participants aged 18-59 years who had neither received any COVID-19 vaccine nor been infected before. They were divided into a low-dose group (administered with either the CS-2034 vaccine containing 30 µg of mRNA or a placebo of 0.3 ml type 5 adenovirus vector) and a high-dose group (administered with either the CS-2034 vaccine containing 50 µg of mRNA or a placebo of 0.5 ml type 5 adenovirus vector). Participants were randomly assigned in a 3:1 ratio to receive either the mRNA vaccine or a placebo on days 0 and 21 according to a two-dose immunization schedule. The first six participants in each dosage group were assigned as sentinel subjects. Participants were sequentially enrolled in a dose-escalation manner from low to high dose and from sentinel to non-sentinel subjects. Blood samples were collected from all participants on the day before the first dose (Day 0), the day before the second dose (day 21), 14 days after the second dose (day 35), and 28 days after the second dose (day 49) to evaluate the immunogenicity of the CS-2034 vaccine. Participants were monitored for safety throughout the 28-day follow-up period, including solicited adverse events, unsolicited adverse events, adverse events of special interest (AESI), and medically attended adverse events (MAE). This report focuses solely on the safety and immunogenicity analysis of adult participants aged 18-59 years, while the long-term phase of the study is still ongoing. This study is registered at ClinicalTrials.gov, NCT05373485. FINDINGS: During the period from May 17, 2022, to August 8, 2022, a total of 155 participants aged 18-59 years were screened for this study. Among them, 115 participants failed the screening process, and 40 participants were randomly enrolled (15 in the low-dose group, 15 in the high-dose group, and 10 in the placebo group). Throughout the 28-day follow-up period, the overall incidence of adverse reactions (related to vaccine administration) in the low-dose group, high-dose group, and placebo group was 93.33% (14/15), 100.00% (15/15), and 80.00% (8/10), respectively. There was a statistically significant difference in the incidence of local adverse reactions (soreness, pruritus, swelling at the injection site) among the low-dose group, high-dose group, and placebo group (P = 0.002). All adverse reactions were mainly of severity grade 1 (mild) or 2 (moderate), and no adverse events of severity grade 4 or higher occurred. Based on the analysis of Spike protein Receptor Binding Domain (S-RBD) IgG antibodies against the BA.1 strain, the seroconversion rates of antibodies at day 21 after the first dose were 86.67%, 93.33%, and 0.00% in the low-dose group, high-dose group, and placebo group, respectively. The geometric mean titer (GMT) of antibodies was 61.2(95%CI 35.3-106.2), 55.4(95%CI 36.3-84.4), and 15.0(95%CI 15.0-15.0), and the geometric mean fold increase (GMI) was 4.08(95%CI 2.35-7.08), 3.69(95%CI 2.42-5.63), and 1.00(95%CI 1.00-1.00) for each group. At day 28 after the full vaccination, the seroconversion rates of antibodies were 100.00%, 93.33%, and 0.00%, and the GMT of antibodies was 810.0(95%CI 511.4-1283.0), 832.2(95%CI 368.1-1881.6), and 15.0(95%CI 15.0-15.0), and the GMI was 54.00(95%CI 34.09-85.53), 55.48(95%CI 24.54-125.44), and 1.00(95%CI 1.00-1.00) for each group, respectively. Based on the analysis of CD3+/CD4+ cell cytokine response, the percentages of IL-2+, IL-4+, IFN-γ+, and TNF-α+ cells increased after 14 days and 28 days of full vaccination in both the low-dose group and high-dose group. The increase was most pronounced in the high-dose group. INTERPRETATION: At day 28 after the full vaccination, both the low-dose and the high-dose CS-2034 vaccine were able to induce the production of high titers of S-RBD IgG antibodies against the BA.1 strain. Adverse reactions in the low-dose and high-dose groups were mainly of severity grade 1 or 2, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine.

Targeting STING in cancer: Challenges and emerging opportunities.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is a key pathway through which the host regulates immune responses by recognizing cytoplasmic double-stranded DNA of abnormal origin, and it plays an important role in tumor growth as well as metastasis, with relevant molecular details constantly being explored and updated. The significant immunomodulatory effects make STING an attractive target for cancer immunotherapy, and STING agonists have been receiving great attention for their development and clinical translation. Despite exciting results in preclinical work, the application of STING agonists to cancer therapy remains challenging due to their poor pharmacokinetic and physicochemical properties, as well as toxic side effects they produce. Here, we summarize the dichotomous role of cGAS-STING in cancer and discuss the limitations of cancer immunotherapy based on STING activation as well as feasible strategies to overcome them to achieve tumor regression.

Function of reactive oxygen species in myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous myeloid cell population and serve as a vital contributor to the tumor microenvironment. Reactive oxygen species (ROS) are byproducts of aerobic respiration and are involved in regulating normal biological activities and disease progression. MDSCs can produce ROS to fulfill their immunosuppressive activity and eliminate excessive ROS to survive comfily through the redox system. This review focuses on how MDSCs survive and function in high levels of ROS and summarizes immunotherapy targeting ROS in MDSCs. The distinctive role of ROS in MDSCs will inspire us to widely apply the blocked oxidative stress strategy in targeting MDSC therapy to future clinical therapeutics.

Development and validation of a nomogram to predict Chinese breast cancer risk based on clinical serum biomarkers.

Background: This study investigated and compared clinical serum biomarkers and developed a diagnostic nomogram for breast cancer. Methods: A total of 1224 breast cancer and 1280 healthy controls were enrolled. Univariate and multivariate analyses were performed to identify factors and a nomogram was developed. Discrimination, accuracy and clinical utility values were evaluated by receiver operating characteristic, Hosmer-Lemeshow, calibration plots, decision curve analysis and clinical impact plots. Results: carcinoembryonic antigen, CA125, CA153, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, fibrinogen and platelet distributing width were effectively identified to predict breast cancer. The nomogram showed the area under the curve of 0.708 and 0.710 in the training and validation set. Calibration plots, Hosmer-Lemeshow, decision curve analysis and clinical impact plots confirmed great accuracy and clinical utility. Conclusion: We developed and validated a nomogram that is effectively used for risk prediction of Chinese breast cancer.

Association of the gut microbiome with fecal short-chain fatty acids, lipopolysaccharides, and obesity in young Chinese college students.

Introduction: Obesity is a growing health problem among young people worldwide and is associated with gut conditions. This study aimed to explore the relationship between obesity, intestinal microbiota, fecal short-chain fatty acids (SCFAs), and lipopolysaccharide (LPS) in young college students. Methods: 16S rRNA gene sequences, SCFA and LPS contents, and obesity status were analyzed in 68 young college students (20-25 years old). Results: There were significant differences in intestinal microbial beta diversity among students with different body mass index (BMI). The abundance and proportion of Firmicutes and Bacteroides had no significant correlation with BMI. The contents of butyric acid and valeric acid in the feces of obese students were low, and the content of SCFAs had no significant correlation with BMI and LPS. The content of LPS in the feces of obese people was significantly higher than that in healthy people, and there was a significant positive correlation between LPS content and BMI. Conclusion: In general, there was a correlation between intestinal microbiota, SCFA, LPS, and BMI in young college students. Our results may enrich the understanding of the relationship between intestinal conditions and obesity and contribute to the study of obesity in young college students.

Corrigendum to "Experience and lessons learned from blunt cerebrovascular injuries: A case report" [Heliyon 9 (3) (March 2023) Article e13968].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e13968.].

When marbles challenge pearls.

The spectacular nature of non-wetting drops mainly arises from their extreme mobility, and quick-silver, for instance, was named after this property. There are two ways to make water non-wetting, and they both rely on texture: either we can roughen a hydrophobic solid, which makes drops looking like pearls, or we can texture the liquid with a hydrophobic powder that "isolates" the resulting marble from its substrate. We observe, here, races between pearls and marbles, and report two effects: (1) the static adhesion of the two objects is different in nature, which we interpret as a consequence of the way they meet their substrates; (2) when they move, pearls are generally quicker than marbles, which might arise from the dissimilarity of the liquid/air interface between these two kinds of globules.

Diagnostic accuracy of contrast-enhanced dual-energy computed tomography for detecting metastatic lymph nodes in patients with malignant tumors: a systematic review and meta-analysis.

Background: This meta-analysis evaluated the diagnostic accuracy of contrast-enhanced dual-energy computed tomography (DECT) for detecting metastatic lymph nodes in patients with cancer. Methods: PubMed, Embase and Cochrane Library databases were searched for literature published from database inception until September 2022. Only studies that investigated the diagnostic accuracy of DECT for metastatic lymph nodes in patients with malignant tumors and surgically removed metastatic lymph nodes for pathological confirmation were included. The quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies tool. The threshold effect was determined by calculating Spearman correlation coefficients and summary receiver operating characteristic (SROC) curve patterns. Deeks test was used to assess publication bias. Results: All of the included studies were observational studies. A total of 16 articles involving 984 patients were included (2,577 lymph nodes) in this review. A total of 15 variables were included in the meta-analysis, including 6 individual parameters and 9 combined parameters. Normalized iodine concentration (NIC) in the arterial phase combined with the slope in the arterial phase showed better identification of metastatic lymph nodes. The spearman correlation coefficient was -0.371 (P=0.468), and the SROC curve did not show a "shoulder-arm" shape, suggesting that there was no threshold effect and that heterogeneity was present. The combined sensitivity was 94% [95% confidence interval (CI): 86-98%], the specificity was 74% (95% CI: 52-88%), and the area under the curve was 0.94. The Deeks test suggested no significant publication bias in the included studies (P=0.06). Conclusions: NIC in arterial phase combined with the slope in the arterial phase has some diagnostic value in differentiating between metastatic and benign lymph nodes, but this should be further evaluated in additional studies with rigorous design and high homogeneity.

Polymer optical fiber detector adapted for low-dose-rate gamma-ray detection.

In this Letter, a polymer optical fiber (POF) detector with a convex spherical aperture microstructure probe is designed for low-energy and low-dose rate gamma-ray detection. Simulation and experimental results demonstrate that this structure has a higher optical coupling efficiency and that the angular coherence of the detector depends strongly on the depth of the probe micro-aperture. By modeling the relationship between angular coherence and micro-aperture depth, the optimal depth of the micro-aperture is determined. The sensitivity of the fabricated POF detector is 701 cps at 59.5-keV gamma-ray of 2.78 µSv/h and the maximum percentage error of the average count rate at different angles is 5.16%.

A high-quality chromosome-level Eutrema salsugineum genome, an extremophile plant model.

BACKGROUND: Eutrema salsugineum (2n = 14), a halophyte in the family Brassicaceae, is an attractive model to study abiotic stress tolerance in plants. Two versions of E. salsugineum genomes that previously reported were based on relatively short reads; thus, the repetitive regions were difficult to characterize. RESULTS: We report the sequencing and assembly of the E. salsugineum (Shandong accession) genome using long-read sequencing and chromosome conformation capture data. We generated Oxford Nanopore long reads at high depth (> 60X) of genome coverage with additional short reads for error correction. The new assembly has a total size of 295.5 Mb with 52.8% repetitive sequences, and the karyotype of E. salsugineum is consistent with the ancestral translocation Proto-Calepineae Karyotype structure in both order and orientation. Compared with previous assemblies, this assembly has higher contiguity, especially in the centromere region. Based on this new assembly, we predicted 25,399 protein-coding genes and identified the positively selected genes associated with salt and drought stress responses. CONCLUSION: The new genome assembly will provide a valuable resource for future genomic studies and facilitate comparative genomic analysis with other plants.

Experience and lessons learned from blunt cerebrovascular injuries: A case report.

Background: Blunt cerebrovascular injuries are rare and serious complications of trauma that can lead to cerebral vascular dissection or aneurysm. Improving awareness of blunt cerebrovascular injuries and using computed tomography angiography to pre-screen patients at high risk is recommended by current guidelines to prevent the occurrence of ischemic stroke complications. Case description: A 32-year-old male patient was admitted to the hospital following neck trauma accompanied by stroke symptoms. Imaging revealed intimal injury of the right common carotid artery and acute cerebral infarction. After an endarterectomy and repair, the vascular lumen obstruction resolved, blood flow was restored, and the patient's condition stabilized. Conclusion: Blunt cerebrovascular injury has been seriously neglected in clinical practice. Delayed or under-diagnosis of blunt cerebrovascular injury can result large strokes. Standardized treatment protocols, which include the screening and grading of blunt cerebrovascular injury, may reduce the risk of permanent neurological dysfunction, and even death, in patients.

Protection of electroactive biofilms against hypersaline shock by quorum sensing.

Quorum sensing (QS) is an ideal strategy for boosting the operating performance of electroactive biofilms (EABs), but its potential effects on the protection of electroactive biofilms against environmental shocks (e.g., hypersaline shock) have been rarely revealed. In this study, a QS signaling molecule, the N-(3-oxo-dodecanoyl)-L-homoserine lactone, was employed to promote the anti-shock property of the EABs against extreme saline shock. The maximum current density of the QS-regulated biofilm recovered to 0.17 mA/cm2 after 10% salinity exposure, which was much higher than those of its counterparts. The laser scanning confocal microscope confirmed a thicker and more compact biofilm with the presence of the QS signaling molecule. The extracellular polymeric substances (EPS) might play a crucial role in the anti-shocking behaviors, as the polysaccharides in EPS of QS-biofilm had doubled compared to the groups with acylase (the QS quencher). The microbial community analysis indicated that the QS molecule enriched the relative abundance of key species including Pseudomonas sp. and Geobacter sp., which were both beneficial to the stability and electroactivity of the biofilms. The functional genes related to the bacterial community were also up-regulated with the presence of the QS molecule. These results highlight the importance of QS effects in protecting electroactive biofilm under extreme environmental shock, which provides effective and feasible strategies for the future development of microbial electrochemical technologies.