Influence of surface polyurea coating on the ballistic performance of kevlar fabric.

With the increasing lethality of modern weapons, the development of body armor has become increasingly important. The main objective of current research is to make protective gear lighter and increase material ballistic performance. Here, a model ballistic-resistant composite material was produced consisting of a polyurea coating on Kevlar plain weave fabric. The effects of coating location and thickness on the ballistic performance of this aramid fabric was examined using yarn pull-out test, ballistic impact test, and numerical simulation. The results demonstrated that the polyurea coating significantly increased the friction between yarns. The maximum yarn pull-out force of the polyurea-coated fiber composite was 40-fold greater than that of the uncoated fiber. Moreover, the application of the coating on the front side outperformed the rear side in terms of ballistic performance. In particular, the front-side 0.2 mm coating was observed to result in the most considerable ballistic limit improvement, increasing the ballistic limit of a single layer of Kevlar fabric from 90.8 to 143.45 m/s. A high precision mesoscale simulation model was developed to analyze the impact of the polyurea coating on the deformation and damage of the Kevlar fabric. These results will contribute to developing new bullet-proof composite materials for the safety protection of personnel.

Heavy Metal Remediation by Dry Mycelium Membranes: Approaches to Sustainable Lead Remediation in Water.

Lead contamination poses significant and lasting health risks, particularly in children. This study explores the efficacy of dried mycelium membranes, distinct from live fungal biomass, for the remediation of lead (Pb(II)) in water. Dried mycelium offers unique advantages, including environmental resilience, ease of handling, biodegradability, and mechanical reliability. The study explores Pb(II) removal mechanisms through sorption and mineralization by dried mycelium hyphae in aqueous solutions. The sorption isotherm studies reveal a high Pb(II) removal efficiency, exceeding 95% for concentrations below 1000 ppm and ∼63% above 1500 ppm, primarily driven by electrostatic interactions. The measured infrared peak shifts and the pseudo-second-order kinetics for sorption suggests a correlation between sorption capacity and the density of interacting functional groups. The study also explores novel surface functionalization of the mycelium network with phosphate to enhance Pb(II) removal, which enables remediation efficiencies >95% for concentrations above 1500 ppm. Scanning electron microscopy images show a pH-dependent formation of Pb-based crystals uniformly deposited throughout the entire mycelium network. Continuous cross-flow filtration tests employing a dried mycelium membrane demonstrate its efficacy as a microporous membrane for Pb(II) removal, reaching remediation efficiency of 85-90% at the highest Pb(II) concentrations. These findings suggest that dried mycelium membranes can be a viable alternative to synthetic membranes in heavy metal remediation, with potential environmental and water treatment applications.

Efficacy of the traditional Chinese medicine, Buyang Huanwu Decoction, at preventing taxane-induced peripheral neuropathy in breast cancer patients: A prospective, randomized, controlled study.

BACKGROUND: Buyang Huanwu Decoction (BYHWD) is a traditional Chinese prescription, originally derived from Yi Lin Gai Cuo during the Qing Dynasty. This study aimed to evaluate the efficacy and safety of BYHWD in the prevention of taxane-induced peripheral neuropathy (TIPN) in patients with breast cancer. METHODS: This single-center, statistician-blinded, parallel-group, simple randomized, no-treatment controlled study was conducted at the China-Japan Friendship Hospital in Beijing. Sixty breast cancer patients scheduled to receive nab-paclitaxel-based chemotherapy were randomly assigned to either the BYHWD group (N = 30) or the control group (N = 30) using simple randomization procedures. The data analysts were unaware of the treatment allocation. The primary efficacy endpoints were the incidence and severity of TIPN in the 2 groups, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and Patients' Neurotoxicity Questionnaire (PNQ). The secondary efficacy endpoint was the score of Functional Assessment of Cancer Therapy-Breast for both groups. The primary safety endpoints were routine blood test results and liver and renal functions. Both groups were subjected to 4 chemotherapy cycles. Efficacy and safety analyses were conducted on an intention-to-treat basis. RESULTS: The incidence of TIPN in the BYHWD group was 50.0%, which was lower than the 80.0% incidence in the control group (ß = -1.881 [95%CI -3.274, -.488]; P = .008, adjusted). The probability of TIPN in the BYHWD group was 15.2% of that in the control group, representing a significant reduction in incidence (odds ratio = .152, [95%CI .038, 0.614]; P = .008, adjusted). The CTCAE and PNQ grades of the BYHWD group were 1.527 and 1.495 points lower than those of the control group at the same cycle, respectively (CTCAE: ß = -1.527 [95%CI -2.522, -.533]; P = .003, adjusted; PNQ: ß = -1.495 [95%CI -2.501, -.489]; P = .004, adjusted, respectively). After treatment, the Functional Assessment of Cancer Therapy-Breast scores in the BYHWD group were significantly better than those in the control group (P = .003), especially in the physiological, functional, and additional concerns domains. CONCLUSION: Buyang Huanwu decoction (BYHWD) can effectively prevent TIPN and improve the quality of life in patients with breast cancer.

Gut microbiota-derived butyrate promotes coronavirus TGEV infection through impairing RIG-I-triggered local type I interferon responses via class I HDAC inhibition.

Gut microbiota-derived metabolites are important for the replication and pathogenesis of many viruses. However, the roles of bacterial metabolites in swine enteric coronavirus (SECoV) infection remain poorly understood. Recent studies show that SECoVs infection in vivo significantly alters the composition of short-chain fatty acids (SCFAs)-producing gut microbiota. This prompted us to investigate whether and how SCFAs impact SECoV infection. Employing alphacoronavirus transmissible gastroenteritis virus (TGEV), a major cause of diarrhea in piglets, as a model, we found that SCFAs, particularly butyrate, enhanced TGEV infection both in porcine intestinal epithelial cells and swine testicular (ST) cells at the late stage of viral infection. This effect depended on the inhibited productions of virus-induced type I interferon (IFN) and downstream antiviral IFN-stimulated genes (ISGs) by butyrate. Mechanistically, butyrate suppressed the expression of retinoic acid-inducible gene I (RIG-I), a key viral RNA sensor, and downstream mitochondrial antiviral-signaling (MAVS) aggregation, thereby impairing type I IFN responses and increasing TGEV replication. Using pharmacological and genetic approaches, we showed that butyrate inhibited RIG-I-induced type I IFN signaling by suppressing class I histone deacetylase (HDAC). In summary, we identified a novel mechanism where butyrate enhances TGEV infection by suppressing RIG-I-mediated type I IFN responses. Our findings highlight that gut microbiota-derived metabolites like butyrate can be exploited by SECoV to dampen innate antiviral immunity and establish infection in the intestine.IMPORTANCESwine enteric coronaviruses (SECoVs) infection in vivo alters the composition of short-chain fatty acids (SCFAs)-producing gut microbiota, but whether microbiota-derived SCFAs impact coronavirus gastrointestinal infection is largely unknown. Here, we demonstrated that SCFAs, particularly butyrate, substantially increased alphacoronavirus TGEV infection at the late stage of infection, without affecting viral attachment or internalization. Furthermore, enhancement of TGEV by butyrate depended on impeding virus-induced type I interferon (IFN) responses. Mechanistically, butyrate suppressed the cytoplasmic viral RNA sensor RIG-I expression and downstream type I IFN signaling activation by inhibiting class I HDAC, thereby promoting TGEV infection. Our work reveals novel functions of gut microbiota-derived SCFAs in enhancing enteric coronavirus infection by impairing RIG-I-dependent type I IFN responses. This implies that bacterial metabolites could be therapeutic targets against SECoV infection by modulating antiviral immunity in the intestine.

Plasma proteomics-based biomarkers for predicting response to mesenchymal stem cell therapy in severe COVID-19.

BACKGROUND: The objective of this study was to identify potential biomarkers for predicting response to MSC therapy by pre-MSC treatment plasma proteomic profile in severe COVID-19 in order to optimize treatment choice. METHODS: A total of 58 patients selected from our previous RCT cohort were enrolled in this study. MSC responders (n = 35) were defined as whose resolution of lung consolidation ≥ 51.99% (the median value for resolution of lung consolidation) from pre-MSC to 28 days post-MSC treatment, while non-responders (n = 23) were defined as whose resolution of lung consolidation < 51.99%. Plasma before MSC treatment was detected using data-independent acquisition (DIA) proteomics. Multivariate logistic regression analysis was used to identify pre-MSC treatment plasma proteomic biomarkers that might distinguish between responders and non-responders to MSC therapy. RESULTS: In total, 1101 proteins were identified in plasma. Compared with the non-responders, the responders had three upregulated proteins (CSPG2, CTRB1, and OSCAR) and 10 downregulated proteins (ANXA1, AGRG6, CAPG, DDX55, KV133, LEG10, OXSR1, PICAL, PTGDS, and S100A8) in plasma before MSC treatment. Using logistic regression model, lower levels of DDX55, AGRG6, PICAL, and ANXA1 and higher levels of CTRB1 pre-MSC treatment were predictors of responders to MSC therapy, with AUC of the ROC at 0.910 (95% CI 0.818-1.000) in the training set. In the validation set, AUC of the ROC was 0.767 (95% CI 0.459-1.000). CONCLUSIONS: The responsiveness to MSC therapy appears to depend on baseline level of DDX55, AGRG6, PICAL, CTRB1, and ANXA1. Clinicians should take these factors into consideration when making decision to initiate MSC therapy in patients with severe COVID-19.

Human umbilical cord-derived mesenchymal stem cells for the treatment of decompensated cirrhosis (MSC-DLC-1): a dose-escalation, phase I trial protocol.

INTRODUCTION: There are limited therapeutic options to efficiently treat patients with decompensated liver cirrhosis. This trial aims to explore the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for the treatment of patients with decompensated liver cirrhosis. METHODS AND ANALYSIS: This study is an open-label, dose-escalation, one-armed phase I trial. A single injection of UC-MSCs will be administered in a predetermined dose in each cohort (5.0×107, 1.0×108, 1.5×108 or 2.0×108 cells) according to the '3+3' rule. The primary evaluation measures will include the incidence of adverse events and the change in the Model for End-stage Liver Disease (MELD) score from baseline to the 28th day. Secondary evaluation measures will be evaluated at baseline and at each follow-up point. These measures will include the change in the MELD score from baseline to each follow-up point, the incidence of each complication associated with decompensated cirrhosis, liver transplant-free survival and the incidence of liver failure, among other relevant measures. All patients will be followed up for 24 months. This study will evaluate whether the use of UC-MSCs to treat patients with decompensated liver cirrhosis is safe and tolerable. ETHICS AND DISSEMINATION: The study has been approved by the Chinese People's Liberation Army General Hospital (Approval#: 2018-107-D-4). Once conducted, the results from the study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05227846.

The relationship between central obesity and risk of breast cancer: a dose-response meta-analysis of 7,989,315 women.

Purpose: Central obesity may contribute to breast cancer (BC); however, there is no dose-response relationship. This meta-analysis examined the effects of central obesity on BC and their potential dose-response relationship. Methods: In the present study, PubMed, Medline, Embase, and Web of Science were searched on 1 August 2022 for published articles. We included the prospective cohort and case-control studies that reported the relationship between central obesity and BC. Summary effect size estimates were expressed as risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals (95% CI) and were evaluated using random-effect models. The inconsistency index (I2) was used to quantify the heterogeneity magnitude derived from the random-effects Mantel-Haenszel model. Results: This meta-analysis included 57 studies (26 case-control and 31 prospective cohort) as of August 2022. Case-control studies indicated that waist circumference (WC) (adjusted OR = 1.18; 95% CI: 1.00-1.38; P = 0.051) and waist-to-hip ratio (WHR) (adjusted OR = 1.28; 95% CI: 1.07-1.53; P = 0.008) were significantly positively related to BC. Subgroup analysis showed that central obesity measured by WC increased the premenopausal (adjusted OR = 1.15; 95% CI: 0.99-1.34; P = 0.063) and postmenopausal (adjusted OR = 1.18; 95% CI: 1.03-1.36; P = 0.018) BC risk and the same relationship appeared in WHR between premenopausal (adjusted OR = 1.38; 95% CI: 1.19-1.59; P < 0.001) and postmenopausal (adjusted OR = 1.41; 95% CI: 1.22-1.64; P < 0.001). The same relationship was observed in hormone receptor-positive (HR+) (adjusted ORWC = 1.26; 95% CI: 1.02-1.57; P = 0.035, adjusted ORWHR = 1.41; 95% CI: 1.00-1.98; P = 0.051) and hormone receptor-negative (HR-) (adjusted ORWC = 1.44; 95% CI: 1.13-1.83; P = 0.003, adjusted ORWHR = 1.42; 95% CI: 0.95-2.13; P = 0.087) BCs. Prospective cohort studies indicated that high WC (adjusted RR = 1.12; 95% CI: 1.08-1.16; P < 0.001) and WHR (adjusted RR = 1.05; 95% CI: 1.018-1.09; P = 0.017) may increase BC risk. Subgroup analysis demonstrated a significant correlation during premenopausal (adjusted RR = 1.08; 95% CI: 1.02-1.14; P = 0.007) and postmenopausal (adjusted RR = 1.14; 95% CI: 1.10-1.19; P < 0.001) between BC and central obesity measured by WC, and WHR was significantly positively related to BC both premenopausal (adjusted RRpre = 1.04; 95% CI: 0.98-1.11; P = 0.169) and postmenopausal (adjusted RRpost = 1.04; 95% CI: 1.02-1.07; P = 0.002). Regarding molecular subtype, central obesity was significantly associated with HR+ (adjusted ORWC = 1.13; 95% CI: 1.07-1.19; P < 0.001, adjusted ORWHR = 1.03; 95% CI: 0.98-1.07; P = 0.244) and HR- BCs (adjusted ORWC =1.11; 95% CI: 0.99-1.24; P = 0.086, adjusted ORWHR =1.01; 95% CI: 0.91-1.13; P = 0.808). Our dose-response analysis revealed a J-shaped trend in the relationship between central obesity and BC (measured by WC and WHR) in case-control studies and an inverted J-shaped trend between BMI (during premenopausal) and BC in the prospective cohort. Conclusion: Central obesity is a risk factor for premenopausal and postmenopausal BC, and WC and WHR may predict it. Regarding the BC subtype, central obesity is proven to be a risk of ER+ and ER- BCs. The dose-response analysis revealed that when BMI (during premenopausal) exceeded 23.40 kg/m2, the risk of BC began to decrease, and WC higher than 83.80 cm or WHR exceeded 0.78 could efficiently increase the BC risk. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022365788.

Detection of Gas Pipeline Leakage Using Distributed Optical Fiber Sensors: Multi-Physics Analysis of Leakage-Fiber Coupling Mechanism in Soil Environment.

Optical fiber sensors are newly established gas pipeline leakage monitoring technologies with advantages, including high detection sensitivity to weak leaks and suitability for harsh environments. This work presents a systematic numerical study on the multi-physics propagation and coupling process of the leakage-included stress wave to the fiber under test (FUT) through the soil layer. The results indicate that the transmitted pressure amplitude (hence the axial stress acted on FUT) and the frequency response of the transient strain signal strongly depends on the types of soil. Furthermore, it is found that soil with a higher viscous resistance is more favorable to the propagation of spherical stress waves, allowing FUT to be installed at a longer distance from the pipeline, given the sensor detection limit. By setting the detection limit of the distributed acoustic sensor to 1 nε, the feasible range between FUT and the pipeline for clay, loamy soil and silty sand is numerically determined. The gas-leakage-included temperature variation by the Joule-Thomson effect is also analyzed. Results provide a quantitative criterion on the installation condition of distributed fiber sensors buried in soil for the great-demanding gas pipeline leakage monitoring applications.

An RBD bispecific antibody effectively neutralizes a SARS-CoV-2 Omicron variant.

Potent neutralizing antibodies (nAbs) against SARS-CoV-2 are a promising therapeutic against the ongoing COVID-19 pandemic. However, the continuous emergence of neutralizing antibody escape variants makes it challenging for antibody therapeutics based on monospecific nAbs. Here, we generated an IgG-like bispecific antibody (bsAb), Bi-Nab, based on a pair of human neutralizing antibodies targeting multiple and invariant sites of the spike receptor binding domain (RBD): 35B5 and 32C7. We demonstrated that Bi-Nab exhibited higher binding affinity to the Delta spike protein than its parental antibodies and presented an extended inhibition breadth of preventing RBD binding to angiotensin-converting enzyme 2 (ACE2), the cellular receptor of SARS-CoV-2. In addition, pseudovirus neutralization results showed that Bi-Nab improved the neutralization potency and breadth with a lower half maximum inhibitory concentration (IC50) against wild-type SARS-CoV-2, variants being monitored (VBMs) and variants of concern (VOCs). Notably, the IgG-like Bi-Nab enhanced the neutralizing activity against Omicron variants with potent capabilities for transmission and immune evasion in comparison with its parental monoclonal antibody (mAb) 32C7 and a cocktail (with the lowest IC50 values of 31.6 ng/mL against the Omicron BA.1 and 399.2 ng/mL against the Omicron BA.2), showing evidence of synergistic neutralization potency of Bi-Nab against the Omicron variants. Thus, Bi-Nab represents a feasible and effective strategy against SARS-CoV-2 variants of concern.

Identification of two novel T cell epitopes on the E2 protein of classical swine fever virus C-strain.

C-strain, also known as the HCLV strain, is a well-known live attenuated vaccine against classical swine fever (CSF), a devastating disease caused by classical swine fever virus (CSFV). Vaccination with C-strain induces a rapid onset of protection, which is associated with virus-specific gamma interferon (IFN-γ)-secreting CD8+ T cell responses. The E2 protein of CSFV is a major protective antigen. However, the T cell epitopes on the E2 protein remain largely unknown. In this study, eight overlapping nonapeptides of the E2 protein were predicted and synthesized to screen for potential T cell epitopes on the CSFV C-strain E2 protein. Molecular docking was performed on the candidate epitopes with the swine leukocyte antigen-1*0401. The analysis obtained two highly conserved T cell epitopes, 90STEEMGDDF98 and 331ATDRHSDYF339, which were further identified by enzyme-linked immunospot assay. Interestingly, the mutants deleting or substituting the epitopes are nonviable. Further analysis demonstrated that 90STEEMGDDF98 is crucial for the E2 homodimerization, while CSFV infection is significantly inhibited by the 331ATDRHSDYF339 peptide treatment. The two novel T cell epitopes can be used to design new vaccines that are able to provide rapid-onset protection.

Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT04288102). METHODS: A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs). FINDINGS: Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups. INTERPRETATION: Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period. FUNDING: The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6).

Association between physiological and perceptual heat strain while wearing stab-resistant body armor.

In this study, we explored the association between physiological and perceptual heat strain while wearing stab-resistant body armor (SRBA). Human trials were performed on ten participants in warm and hot environments. Physiological responses (core temperature, skin temperature, and heart rate), and perceptual responses (thermal sensation vote, thermal comfort vote, restriction of perceived exertion (RPE), wetness of skin, and wetness of clothing) were recorded throughout the trials, and subsequently, the physiological strain index (PSI), and perceptual strain index (PeSI) were calculated. The results indicated that the PeSI showed a significant moderate association with the PSI, and was capable of predicting PSI for low (PSI = 3) and high (PSI = 7) levels of physiological strain with the areas under the curves of 0.80 and 0.64, respectively. Moreover, Bland-Altman analysis indicated that the majority of the PSI ranged within the 95% confidence interval, and the mean difference between PSI and PeSI was 0.14 ± 2.02 with the lower 95% limit and upper 95% limit being -3.82 to 4.10, respectively. Therefore, the subjective responses could be used as an indicator for predicting physiological strain while wearing SRBA. This study could provide fundamental knowledge for the usage of SRBA, and the development of physiological heat strain assessment.

Discovery of Novel Resistance Mechanisms of Vibrio parahaemolyticus Biofilm against Aminoglycoside Antibiotics.

Inappropriate use of antibiotics eventually leads to the emergence of antibiotic-resistant strains and invalidates the treatment of infectious diseases. Aminoglycoside antibiotics (AGAs) are a class of broad-spectrum cationic antibiotics widely used for the treatment of Gram-negative bacterial infections. Understanding the AGA resistance mechanism of bacteria would increase the efficacy of treating these infections. This study demonstrates a significant correlation between AGA resistance and the adaptation of biofilms by Vibrio parahaemolyticus (VP). These adaptations were the result of challenges against the aminoglycosides (amikacin and gentamicin). Confocal laser scanning microscope (CLSM) analysis revealed an enclosure type mechanism where the biological volume (BV) and average thickness (AT) of V. parahaemolyticus biofilm were significantly positively correlated with amikacin resistance (BIC) (p < 0.01). A neutralization type mechanism was mediated by anionic extracellular polymeric substances (EPSs). The biofilm minimum inhibitory concentrations of amikacin and gentamicin were reduced from 32 µg/mL to 16 µg/mL and from 16 µg/mL to 4 µg/mL, respectively, after anionic EPS treatment with DNase I and proteinase K. Here, anionic EPSs bind cationic AGAs to develop antibiotic resistance. Transcriptomic sequencing revealed a regulatory type mechanism, where antibiotic resistance associated genes were significantly upregulated in biofilm producing V. parahaemolyticus when compared with planktonic cells. The three mechanistic strategies of developing resistance demonstrate that selective and judicious use of new antibiotics are needed to win the battle against infectious disease.

Fish oil fat emulsion alleviates traumatic brain injury in mice by regulation of microglia polarization.

Microglia activation, a hallmark of brain neuroinflammation, contributes to the secondary damage following traumatic brain injury (TBI). To explore the potential roles of different fat emulsions-long chain triglyceride (LCT) / medium chain triglyceride (MCT) and fish oil (FO) fat emulsion in neuroprotection and neuroinflammation in TBI, in this study, we first generated the controlled cortical impact (CCI) model of TBI mice. Then either LCT/MCT or FO fat emulsion treated mice were studied by Nissl staining to assess the lesion volume. Sham and TBI mice treated with 0.9% saline were used as controls. The fatty acid composition in different TBI mouse brains was further evaluated by gas chromatography. Immunofluorescent staining and quantitative RT-PCR both demonstrated the suppression of pro-inflammatory microglia and upregulated anti-inflammatory microglia in FO fat emulsion treated TBI brain or primary microglia induced by lipopolysaccharide (LPS) in vitro. Furthermore, motor and cognitive behavioral tests showed FO fat emulsion could partially improve the motor function in TBI mice. Together, our results indicate that FO fat emulsion significantly alleviates the TBI injury and neuroinflammation probably by regulating microglia polarization.

Antimicrobial resistomes in food chain microbiomes.

The safety and integrity of the global food system is in a constant state of flux with persistent chemical and microbial risks. While chemical risks are being managed systematically, microbial risks pose extra challenges. Antimicrobial resistant microorganism and persistence of related antibiotic resistance genes (ARGs) in the food chain adds an extra dimension to the management of microbial risks. Because the food chain microbiome is a key interface in the global health system, these microbes can affect health in many ways. In this review, we systematically summarize the distribution of ARGs in foods, describe the potential transmission pathway and transfer mechanism of ARGs from farm to fork, and discuss potential food safety problems and challenges. Modulating antimicrobial resistomes in the food chain facilitates a sustainable global food production system.

Spliceosomal GTPase Eftud2 regulates microglial activation and polarization.

Elongation factor Tu GTP binding domain protein 2 (Eftud2) is a spliceosomal GTPase that serves as an innate immune modulator restricting virus infection. Microglia are the resident innate immune cells and the key players of immune response in the central nervous system. However, the role of Eftud2 in microglia has not been reported. In this study, we performed immunofluorescent staining and western blot assay and found that Eftud2 was upregulated in microglia of a 5xFAD transgenic mouse model of Alzheimer's disease. Next, we generated an inducible microglia-specific Eftud2 conditional knockout mouse line (CX3CR1-CreER; Eftud2f/f cKO) via Cre/loxP recombination and found that Eftud2 deficiency resulted in abnormal proliferation and promoted anti-inflammatory phenotype activation of microglia. Furthermore, we knocked down Eftud2 in BV2 microglia with siRNA specifically targeting Eftud2 and found that Eftud2-mediated regulation of microglial proinflammatory/anti-inflammatory phenotype activation in response to inflammation might be dependent on the NF-κB signaling pathway. Our findings suggest that Eftud2 plays a key role in regulating microglial polarization and homeostasis possibly through the NF-κB signaling pathway.

A natriuretic peptide molecule from Vigna angularis, VaEG45, confers rust resistance by inhibiting fungal development.

KEY MESSAGE: Novel function and mechanism of a PNP molecule VaEG45 from adzuki bean involved in plant immunity. Plant natriuretic peptides (PNPs) can affect a broad spectrum of physiological responses in plants acting as peptidic signaling molecules. However, PNPs may play additional roles in plant immunity. Our previous transcriptome data of adzuki bean (Vigna angularis) in response to Uromyces vignae infection revealed association of PNP-encoding gene VaEG45 with U. vignae resistance. To determine the function of VaEG45 in disease resistance, we cloned the 589 bp nucleotide sequence of VaEG45 containing 2 introns, encoding a putative 13.68 kDa protein that is 131 amino acids in length. We analyzed expression in different resistant cultivars of V. angularis and found significant induction of VaEG45 expression after U. vignae infection. Transient expression of VaEG45 improved tobacco resistance against Botrytis cinerea. We next analyzed the mechanism by which VaEG45 protects plants from fungal infection by determination of the biological activity of the prokaryotic expressed VaEG45. The results showed that the fusion protein VaEG45 can significantly inhibit urediospores germination of U. vignae, mycelial growth, and the infection of tobacco by B. cinerea. Further analysis revealed that VaEG45 exhibits ß-1, 3-glucanase activity. These findings uncover the function of a novel PNP molecule VaEG45 and provide new evidence about the mechanism of PNPs in plant immunity.

Identification of the p34 Protein of African Swine Fever Virus as a Novel Viral Antigen with Protection Potential.

African swine fever (ASF) is a highly contagious disease caused by African swine fever virus (ASFV), affecting domestic and wild boars. The polyprotein pp220 of ASFV is responsible for producing the major structural proteins p150, p37, p14, p34, and p5 via proteolytic processing. The p34 protein is the main component of the ASFV core shell. However, the immunologic properties of the p34 protein in vitro and in vivo remain unclear. The results showed that the recombinant p34 protein expressed in prokaryotes and eukaryotes could react with convalescent swine sera to ASFV, suggesting that p34 is an immunogenic protein. Significantly, anti-p34 antibodies were found to inhibit the replication of ASFV in target cells. Furthermore, rabbits immunized with the recombinant C-strain of classical swine fever virus containing p34 produced both anti-p34 humoral and cellular immune responses. In addition, the p34 protein could induce a cell-mediated immune response, and a T-cell epitope on the p34 protein was identified using immunoinformatics and enzyme-linked immunospot (ELIspot) assay. Our study demonstrates that the p34 protein is a novel antigen of ASFV with protective potential.

Adolescent triple-negative breast cancer with germline pathogenic variants in both BRCA1 and TP53 genes: A case report.

Almost 5-10% of breast cancer results from inherited genetic pathogenic variants. Patients with pathogenic variants in high-penetrance genes such as TP53, BRCA1 and BRCA2 are susceptible to breast cancer. Moreover, nearly 80% of BRCA pathogenic variants carriers are diagnosed with breast cancer at a young age before menopause. There is currently no report of early onset breast cancer with germline pathogenic variants in both BRCA1 and TP53 genes. Here, we report a case of a 14-years-old female diagnosed with triple-negative breast cancer with a family history of malignant tumors. The cancer metastasized to multiple lymph nodes 1 year and 4 months after surgery, and the progression-free survival after subsequent chemotherapy and surgery has been 2 years and 10 months. The patient's white blood cells were screened against a panel of 11 cancer-related genes, and both germline pathogenic variants in BRCA1 and TP53 were identified. Genetic tests of her family members revealed the same pathogenic variants in BRCA1 in her father and brother, but BRCA1 pathogenic variants wasn't shown in other family members. The case indicates that genetic testing needs be performed in early onset breast cancer to confirm inherited risk, and if a germline pathogenic variant is identified, tailored therapeutic interventions and preventive interventions should be taken and genetic testing is recommended for relatives.

Natural Inhibitors Targeting the Localization of Lipoprotein System in Vibrio parahaemolyticus.

The localization of lipoprotein (Lol) system is responsible for the transport of lipoproteins in the outer membrane (OM) of Vibrio parahaemolyticus. LolB catalyzes the last step in the Lol system, where lipoproteins are inserted into the OM. If the function of LolB is impeded, growth of V. parahaemolyticus is inhibited, due to lack of an intact OM barrier for protection against the external environment. Additionally, it becomes progressively harder to generate antimicrobial resistance (AMR). In this study, LolB was employed as the receptor for a high-throughput virtual screening from a natural compounds database. Compounds with higher glide score were selected for an inhibition assay against V. parahaemolyticus. It was found that procyanidin, stevioside, troxerutin and rutin had both exciting binding affinity with LolB in the micromolar range and preferable antibacterial activity in a concentration-dependent manner. The inhibition rates of 100 ppm were 87.89%, 86.2%, 91.39% and 83.71%, respectively. The bacteriostatic mechanisms of the four active compounds were explored further via fluorescence spectroscopy and molecular docking, illustrating that each molecule formed a stable complex with LolB via hydrogen bonds and pi-pi stacking interactions. Additionally, the critical sites for interaction with V. parahaemolyticus LolB, Tyr108 and Gln68, were also illustrated. This paper demonstrates the inhibition of LolB, thus, leading to antibacterial activity, and identifies LolB as a promising drug target for the first time. These compounds could be the basis for potential antibacterial agents against V. parahaemolyticus.