Thanatin: A Promising Antimicrobial Peptide Targeting the Achilles' Heel of Multidrug-Resistant Bacteria.

Antimicrobial resistance poses an escalating threat to human health, necessitating the development of novel antimicrobial agents capable of addressing challenges posed by antibiotic-resistant bacteria. Thanatin, a 21-amino acid ß-hairpin insect antimicrobial peptide featuring a single disulfide bond, exhibits broad-spectrum antibacterial activity, particularly effective against multidrug-resistant strains. The outer membrane biosynthesis system is recognized as a critical vulnerability in antibiotic-resistant bacteria, which thanatin targets to exert its antimicrobial effects. This peptide holds significant promise for diverse applications. This review begins with an examination of the structure-activity relationship and synthesis methods of thanatin. Subsequently, it explores thanatin's antimicrobial activity, detailing its various mechanisms of action. Finally, it discusses prospective clinical, environmental, food, and agricultural applications of thanatin, offering valuable insights for future research endeavors.

Unfolding coil localized errors from an imperfect slice profile using a structured autocalibration matrix: An application to reduce outflow effects in cine bSSFP imaging.

PURPOSE: Balanced steady-state free precession (bSSFP) imaging is susceptible to outflow effects where excited spins leaving the slice as part of the blood stream are misprojected back onto the imaging plane. Previous work proposed using slice-encoding steps to localize these outflow effects from corrupting the target slice, at the expense of prolonged scan time. This present study extends this idea by proposing a means of significantly reducing most of the outflowing signal from the imaged slice using a coil localization method that acquires a slice-encoded calibration scan in addition to the 2D data, without being nearly as time-demanding as our previous method. This coil localization method is titled UNfolding Coil Localized Errors from an imperfect slice profile using a Structured Autocalibration Matrix (UNCLE SAM). METHODS: Retrospective and prospective evaluations were carried out. Both featured a 2D acquisition and a separate slice-encoded calibration of the center in-plane k $$ k $$ -space lines across all desired slice-encoding steps. RESULTS: Retrospective results featured a slice-by-slice comparison of the slice-encoded images with UNCLE SAM. UNCLE SAM's subtraction from the slice-encoded image was compared with a subtraction from the flow-corrupted 2D image, to demonstrate UNCLE SAM's capability to unfold outflowing spins. UNCLE SAM's comparison with slice encoding showed that UNCLE SAM was able to unfold up to 74% of what slice encoding achieved. Prospective results showed significant reduction in outflow effects with only a marginal increase in scan time from the 2D acquisition. CONCLUSIONS: We developed a method that effectively unfolds most outflowing spins from corrupting the target slice and does not require the explicit use of slice-encoding gradients. This development offers a method to reduce most outflow effects from the target slice within a clinically feasible scan duration compared with the fully sampled slice-encoding technique.

Mining and multifaceted applications of phage lysin for combatting Vibrio parahaemolyticus.

Vibrio parahaemolyticus, a prevalent foodborne pathogen found in both water and seafood, poses substantial risks to public health. The conventional countermeasure, antibiotics, has exacerbated the issue of antibiotic resistance, increasing the difficulty of controlling this bacterium. Phage lysins, as naturally occurring active proteins, offer a safe and reliable strategy to mitigate the impact of V. parahaemolyticus on public health. However, there is currently a research gap concerning bacteriophage lysins specific to Vibrio species. To address this, our study innovatively and systematically evaluates 37 phage lysins sourced from the NCBI database, revealing a diverse array of conserved domains and notable variations in similarity among Vibrio phage lysins. Three lysins, including Lyz_V_pgrp, Lyz_V_prgp60, and Lyz_V_zlis, were successfully expressed and purified. Optimal enzymatic activity was observed at 45℃, 800 mM NaCl, and pH 8-10, with significant enhancements noted in the presence of 1 mM membrane permeabilizers such as EDTA or organic acids. These lysins demonstrated effective inhibition against 63 V. parahaemolyticus isolates from clinical, food, and environmental sources, including the reversal of partial resistance, synergistic interactions with antibiotics, and disruption of biofilms. Flow cytometry analyses revealed that the combination of Lyz_V_pgp60 and gentamicin markedly increased bacterial killing rates. Notably, Lyz_V_pgrp, Lyz_V_pgp60, and Lyz_V_zlis exhibited highly efficient biofilm hydrolysis, clearing over 90 % of preformed V. parahaemolyticus biofilms within 48 h. Moreover, these lysins significantly reduced bacterial loads in various food samples and environmental sources, with reductions averaging between 1.06 and 1.29 Log CFU/cm2 on surfaces such as stainless-steel and bamboo cutting boards and approximately 0.87 CFU/mL in lake water and sediment samples. These findings underscore the exceptional efficacy and versatile application potential of phage lysins, offering a promising avenue for controlling V. parahaemolyticus contamination in both food and environmental contexts.

The subcommissural organ regulates brain development via secreted peptides.

The subcommissural organ (SCO) is a gland located at the entrance of the aqueduct of Sylvius in the brain. It exists in species as distantly related as amphioxus and humans, but its function is largely unknown. Here, to explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes, Sspo, Car3 and Spdef, that are highly expressed in the SCO. Mouse strains expressing Cre recombinase from endogenous promoter/enhancer elements of these genes were used to genetically ablate SCO cells during embryonic development, resulting in severe hydrocephalus and defects in neuronal migration and development of neuronal axons and dendrites. Unbiased peptidomic analysis revealed enrichment of three SCO-derived peptides, namely, thymosin beta 4, thymosin beta 10 and NP24, and their reintroduction into SCO-ablated brain ventricles substantially rescued developmental defects. Together, these data identify a critical role for the SCO in brain development.

The subcommissural organ regulates brain development via secreted peptides.

The subcommissural organ (SCO) is a gland located at the entrance of the aqueduct of Sylvius in the brain. It exists in species as distantly related as amphioxus and humans, but its function is largely unknown. To explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes, Sspo, Car3, and Spdef, that are highly expressed in the SCO. Mouse strains expressing Cre recombinase from endogenous promoter/enhancer elements of these genes were used to genetically ablate SCO cells during embryonic development, resulting in severe hydrocephalus and defects in neuronal migration and development of neuronal axons and dendrites. Unbiased peptidomic analysis revealed enrichment of three SCO-derived peptides, namely thymosin beta 4, thymosin beta 10, and NP24, and their reintroduction into SCO-ablated brain ventricles substantially rescued developmental defects. Together, these data identify a critical role for the SCO in brain development.

Bimetallic Au and Pd Nanoparticles Modified WO3 Nanosheets for Enhancing the Sensitivity and Selectivity of Formaldehyde Assessment in Aquatic Products.

Formaldehyde, a common illegal additive in aquatic products, poses a threat to people's health and lives. In this study, a novel metal oxide semiconductor gas sensor based on AuPd-modified WO3 nanosheets (NSs) had been developed for the highly efficient detection of formaldehyde. WO3 NS modified with 2.0% AuPd nanoparticles showed a higher response (Ra/Rg = 94.2) to 50 ppm of formaldehyde at 210 °C, which was 36 times more than the pristine WO3 NS. In addition, the AuPd/WO3 gas sensor had a relatively short response/recovery time of 10 s/9 s for 50 ppm of formaldehyde at 210 °C, with good immunity to other interfering gases and good stability for formaldehyde. The excellent gas-sensitive performance was attributed to the chemical sensitization of Au, the electronic sensitization of Pd, and the synergistic effect of bimetallic AuPd, which facilitated the recognition and response of formaldehyde molecules. Additionally, the high sensitivity and broad application prospect of the 2.0% AuPd/WO3 NS composite-based sensor in real sample detection were also confirmed by using the above sensor for the detection of formaldehyde in aquatic products such as squid and shrimp.

Intervention mechanism of marine-based chito-oligosaccharide on acute liver injury induced by AFB1 in rats.

Aflatoxin B1 (AFB1) is extremely hepatotoxic, a causative agent of liver cancer, and can cause symptoms of acute or chronic liver damage. Chito-oligosaccharides (COS), obtained from the degradation of chitosan derived from shrimp and crab shells, is a natural antioxidant substance and its antitumor properties have been widely studied, but less research has been done on the prevention of AFB1-induced acute liver injury. In this study, rats were acutely exposed to 1 mg/kg BW AFB1 and simultaneously gavaged with different doses of COS for 8 days. The results showed that COS attenuated the hepatic histopathological changes and reduced serum biochemical indices (ALT, AST, ALP, and TBIL) in rats. It significantly inhibited MDA content and promoted SOD and GSH-Px activity production. Moreover, it also improved hepatocyte apoptosis. Furthermore, AFB1-vs-HCOS differential genes were enriched with 622 GO entries, and 380 were Biological Processes, 170 were Molecular Functions, 72 were Cellular Components. Differentially expressed genes (DEGs) analyzed by KEGG enrichment were more enriched in pathways, such as metabolism, PPAR signaling pathway, and peroxisome. Q-PCR technique verified that Lama5, Egr1, Cyp2b1, and Gadd45g in DEGs were associated with oxidative stress damage and apoptosis. In conclusion, COS intervention reduces the effect of AFB1 on hepatic genes and thus reduces the changes in hepatic gene function.

Preservation effects of photodynamic inactivation-mediated antibacterial film on storage quality of salmon fillets: Insights into protein quality.

The preservation effects of a photodynamic inactivation (PDI)-mediated polylactic acid/5-aminolevulinic acid (PLA/ALA) film on the storage quality of salmon fillets were investigated. Results showed that the PDI-mediated PLA/ALA film could continuously generate reactive oxygen species by consuming oxygen to inactivate native pathogens and spoilage bacteria on salmon fillets. Meanwhile, the film maintained the content of muscle proteins and their secondary and tertiary structures, as well as the integrity of myosin by keeping the activity of Ca2+-ATPase, all of which protected the muscle proteins from degradation. Furthermore, the film retained the activity of total superoxide dismutase (T-SOD), suppressed the accumulation of lipid peroxides (e.g., MDA), which greatly inhibited four main types of protein oxidations. As a result, the content of flavor amino acids and essential amino acids in salmon fillets was preserved. Therefore, the PDI-mediated antimicrobial packaging film greatly preserves the storage quality of aquatic products by preserving the protein quality.

High-resolution prostate diffusion MRI using eddy current-nulled convex optimized diffusion encoding and random matrix theory-based denoising.

OBJECTIVE: To develop and evaluate a technique combining eddy current-nulled convex optimized diffusion encoding (ENCODE) with random matrix theory (RMT)-based denoising to accelerate and improve the apparent signal-to-noise ratio (aSNR) and apparent diffusion coefficient (ADC) mapping in high-resolution prostate diffusion-weighted MRI (DWI). MATERIALS AND METHODS: Eleven subjects with clinical suspicion of prostate cancer were scanned at 3T with high-resolution (HR) (in-plane: 1.0 × 1.0 mm2) ENCODE and standard-resolution (1.6 × 2.2 mm2) bipolar DWI sequences (both had 7 repetitions for averaging, acquisition time [TA] of 5 min 50 s). HR-ENCODE was retrospectively analyzed using three repetitions (accelerated effective TA of 2 min 30 s). The RMT-based denoising pipeline utilized complex DWI signals and Marchenko-Pastur distribution-based principal component analysis to remove additive Gaussian noise in images from multiple coils, b-values, diffusion encoding directions, and repetitions. HR-ENCODE with RMT-based denoising (HR-ENCODE-RMT) was compared with HR-ENCODE in terms of aSNR in prostate peripheral zone (PZ) and transition zone (TZ). Precision and accuracy of ADC were evaluated by the coefficient of variation (CoV) between repeated measurements and mean difference (MD) compared to the bipolar ADC reference, respectively. Differences were compared using two-sided Wilcoxon signed-rank tests (P < 0.05 considered significant). RESULTS: HR-ENCODE-RMT yielded 62% and 56% higher median aSNR than HR-ENCODE (b = 800 s/mm2) in PZ and TZ, respectively (P < 0.001). HR-ENCODE-RMT achieved 63% and 70% lower ADC-CoV than HR-ENCODE in PZ and TZ, respectively (P < 0.001). HR-ENCODE-RMT ADC and bipolar ADC had low MD of 22.7 × 10-6 mm2/s in PZ and low MD of 90.5 × 10-6 mm2/s in TZ. CONCLUSIONS: HR-ENCODE-RMT can shorten the acquisition time and improve the aSNR of high-resolution prostate DWI and achieve accurate and precise ADC measurements in the prostate.

Ammonia storage and slip under steady and transient state in close-coupled SCR.

The close-coupled selective catalytic reduction (cc-SCR) catalyst is an effective technology to reduce tailpipe NOx emission during cold start. This paper investigated the optimal ammonia storage under steady and transient state in the cc-SCR. The study showed that a trade-off between NOx conversion efficiency and ammonia slip is observed on the pareto solutions under steady state, and the optimal ammonia storage is calculated with ammonia slip less than 10 µL/L based on the China Ⅵ emission legislation. The rapid temperature increase will lead to severe ammonia slip in the transient test cycle. A simplified 0-D calculation method on ammonia slip under transient state is proposed based on kinetic model of ammonia adsorption and desorption. In addition, the effect of ammonia storage, catalyst temperature and temperature increasing rate on ammonia slip are analyzed. The optimal ammonia storage is calculated with maximum ammonia slip less than 100 µL/L according to the oxidation efficiency of ammonia slip catalyst (ASC) downstream cc-SCR. It was found that the optimal ammonia storage under transient state is much lower than that under steady state in cc-SCR at lower temperature, and a phase diagram is established to analyze the influence of temperature and temperature increasing rate on optimal ammonia storage.

Modeling naturally-occurring Vibrio parahaemolyticus in post-harvest raw shrimps.

There is little known about the growth and survival of naturally-occurring Vibrio parahaemolyticus in harvested raw shrimps. In this study, the fate of naturally-occurring V. parahaemolyticus in post-harvest raw shrimps was investigated from 4℃ to 30℃ using real-time PCR combined with propidium monoazide (PMA-qPCR). The Baranyi-model was used to fit the growth and survival data. A square root model and non-linear Arrhenius model was then used to quantify the parameters derived from the Baranyi-model. The results showed that naturally-occurring V. parahaemolyticus were slowly inactivated at 4℃ and 7℃ with deactivation rates of 0.019 Log CFU/g/h and 0.025 Log CFU/g/h. Conversely, at 15, 20, 25, and 30 °C, the average maximum growth rates (µmax) of naturally-occurring V. parahaemolyticus were determined to be 0.044, 0.105, 0.179 and 0.336 Log CFU/g/h, accompanied by the average lag phases (λ) of 15.5 h, 7.3 h, 4.4 h and 3.7 h. The validation metrics, Af and Bf, for both the square root model and non-linear, indicating that the model had a good ability to predict the growth behavior of naturally-occurring V. parahaemolyticus in post-harvest raw shrimps. Furthermore, a comparative exploration between the growth of artificially contaminated V. parahaemolyticus in cooked shrimps and naturally-occurring V. parahaemolyticus in post-harvest raw shrimps revealed intriguing insights. While no substantial distinction in deactivation rates emerged at 4 °C and 7 °C (P > 0.05), a discernible disparity in growth rates was observable at 15 °C, 20 °C, 25 °C, and 30 °C, with the former surpassing the latter. Which indicated the risk of V. parahaemolyticus using models derived from cooked shrimps may be biased. Our study also unveiled a discernible seasonal effect. The µmax and λ of V. parahaemolyticus in shrimps harvested in summer were similar to those harvested in autumn, while the initial and maximum bacterial concentration harvested in summer were higher than those harvested in autumn. This predictive microbiology model of naturally-occurring V. parahaemolyticus in raw shrimps provides relevance to modelling growth in situ.

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.

A dual-modality immunosensor for simple and reliable detection of nitrated alpha-synuclein in serum based on silver-coated MOF.

Nitrated α-syn (nitro-α-syn) is a biomarker for Parkinson's desease (PD), and its sensitive detection in serum is of great importance for early PD diagnosis. Silver-coated copper MOF (Cu-MOF@Ag) with outstanding oxidase activity and electrochemical response property was designed and synthesized. Cu-MOF@Ag exhibited excellent oxidase activity with a low Km value (0.568 mM), avoiding the addition of strong oxidant to catalyze chromogenic substrate, which enhanced the colorimetric stability. Silver nanoparticles as an electrochemical signal reporter can be easily decorated on the surface of Cu-MOF with bifunctional groups (-SH and -NH2) material, which can increase the electrochemical signal output. The α-syn antibody modified Cu-MOF@Ag and nitro-α-syn modified magnetic nanoparticle were used as immunoprobes to specifically capture nitro-α-syn. A dual-modal immunosensor was fabricated for the simple and reliable detection of nitro-α-syn based on Cu-MOF@Ag. Combing colorimetric and electrochemical detection, nitro-α-syn can be determined quantitatively within a wide linear range (10-350 ng/mL) with low detection limit (0.5 ng/mL). The ability of the sensor with magnetic separation and dual signal analysis allowed to successfully detect nitro-α-syn and distinguish PD patients from healthy people (P < 0.005). Thanks to its excellent selectivity, stability, and the precision of 2.69%, the dual-modal sensor has potential clinical application for nitro-α-syn detection and paves a new way for PD diagnosis at its early stage.

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.

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.

Enhanced Response for Foodborne Pathogens Detection by Au Nanoparticles Decorated ZnO Nanosheets Gas Sensor.

Listeria monocytogenes is a hazardous foodborne pathogen that is able to cause acute meningitis, encephalitis, and sepsis to humans. The efficient detection of 3-hydroxy-2-butanone, which has been verified as a biomarker for the exhalation of Listeria monocytogenes, can feasibly evaluate whether the bacteria are contained in food. Herein, we developed an outstanding 3-hydroxy-2-butanone gas sensor based on the microelectromechanical systems using Au/ZnO NS as a sensing material. In this work, ZnO nanosheets were synthesized by a hydrothermal reaction, and Au nanoparticles (~5.5 nm) were prepared via an oleylamine reduction method. Then, an ultrasonic treatment was carried out to modified Au nanoparticles onto ZnO nanosheets. The XRD, BET, TEM, and XPS were used to characterize their morphology, microstructure, catalytic structure, specific surface area, and chemical composition. The response of the 1.0% Au/ZnO NS sensors vs. 25 ppm 3-hydroxy-2-butanone was up to 174.04 at 230 °C. Moreover, these sensors presented fast response/recovery time (6 s/7 s), great selectivity, and an outstanding limit of detection (lower than 0.5 ppm). This work is full of promise for developing a nondestructive, rapid and practical sensor, which would improve Listeria monocytogenes evaluation in foods.

Comprehensive Bioinformatics Analysis Combined with Wet-Lab Experiments to Find Target Proteins of Chinese Medicine Monomer.

How to use bioinformatics methods to quickly and accurately locate the effective targets of traditional Chinese medicine monomer (TCM) is still an urgent problem needing to be solved. Here, we used high-throughput sequencing to identify the genes that were up-regulated after cells were treated with TCM monomers and used bioinformatics methods to analyze which transcription factors activated these genes. Then, the binding proteins of these transcription factors were analyzed and cross-analyzed with the docking proteins predicted by small molecule reverse docking software to quickly and accurately determine the monomer's targets. Followeding this method, we predicted that the TCM monomer Daphnoretin (DT) directly binds to JAK2 with a binding energy of -5.43 kcal/mol, and activates the JAK2/STAT3 signaling transduction pathway. Subsequent Western blotting and in vitro binding and kinase experiments further validated our bioinformatics predictions. Our method provides a new approach for quickly and accurately locating the effective targets of TCM monomers, and we also have discovered for the first time that TCM monomer DT is an agonist of JAK2.

Reusable and universal impedimetric sensing platform for the rapid and sensitive detection of pathogenic bacteria based on bacteria-imprinted polythiophene film.

The rapid and sensitive detection of pathogenic bacteria is highly demanded for early warning of infectious disease epidemics and protection of human health. Herein, a reusable and universal impedimetric sensing platform based on a bacteria-imprinted polythiophene film (BIF) is proposed for the rapid and sensitive detection of pathogenic bacteria using Staphylococcus aureus (S. aureus) as a model analyte. Monomer screening among four 3-substituted thiophenes was first performed based on the imprinting factor, and 3-thiopheneethanol (TE) was eventually selected. The BIF as a recognition layer was quickly deposited in an environmentally friendly process on a glassy carbon electrode via electro-copolymerization of the S. aureus template and TE monomer followed by in situ template removal. Upon rebinding of S. aureus on the BIF, the impedance increased. Under optimal conditions, the BIF-based sensor can quantitatively detect S. aureus in a wide linear range of 10 to 107 CFU mL-1 with a low detection limit of 4 CFU mL-1. Additionally, the sensor exhibits excellent selectivity, capable of identifying S. aureus from multi-bacterial strain mixtures. It also demonstrates applicability in the analysis of real lettuce and shrimp samples with good recoveries. Most significantly, the BIF sensing interface can be reused up to five times with good signal retention. Compared with most reported methods, this sensor is more rapid with a much shorter total assay time of 30 min, including the BIF preparation, bacterial rebinding, and impedance detection. This assay may hold great potential to help in the rapid, sensitive, and label-free detection of pathogenic bacteria in fields of food safety and public health.

The efficacy and safety of gemcitabine-based combination therapy vs. gemcitabine alone for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis.

Background: Gemcitabine (GEM) is used as a standard first-line drug to effectively alleviate symptoms and prolong survival time for advanced pancreatic cancer. Most randomized controlled trials (RCTs) show that GEM-based combination therapy is better than GEM alone, while some RCTs have the opposite conclusion. This study aimed to investigate whether GEM-based combination therapy would be superior to GEM alone by a systematic review and meta-analysis. Methods: According to the PICOS principles, RCTs (S) focused on comparing GEM-based combination therapy (I) vs. GEM alone (C) for advanced pancreatic cancer (P) were collected from eight electronic databases, outcome variables mainly include survival status and adverse events (AEs) (O). Review Manager 5.4 was used to evaluate the pooled effects of the results among selected articles. Pooled estimate of hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were used as measures of effect sizes. Quality assessment for individual study was performed using the Cochrane tool for risk of bias. Results: A total of 17 studies including 5,197 patients were selected in this analysis. The pooled results revealed that GEM-based combination therapy significantly improved the overall survival (OS; HR =0.84; 95% CI: 0.79 to 0.90; P<0.00001), progression-free survival (PFS; HR =0.78; 95% CI: 0.72 to 0.84; P<0.00001), overall response rate (ORR; OR =1.92; 95% CI: 1.61 to 2.30; P<0.00001), 1-year survival rate (OR =1.44; 95% CI: 1.02 to 2.03; P=0.04), respectively. Subgroup analysis showed that the efficacy of GEM plus capecitabine (CAP) and GEM plus S-1 was better than that of GEM alone, while GEM plus cisplatin (CIS) did not achieve an improved effect. GEM-based combination therapy can significantly increase the incidence of AEs, such as leukopenia (P<0.001), neutropenia (P<0.001), anemia (P<0.05), nausea (P<0.001), diarrhea (P<0.05), and stomatitis (P<0.001). No publication bias existed in our meta-analysis (P>0.10). Discussion: Our study supported that GEM-based combination therapy was more beneficial to improve patient's survival than GEM alone, while there was no additional benefits in GEM plus CIS. We also found that GEM-based combination therapy increased the incidence of AEs. Clinicians need to choose the appropriate combination therapy according to the specific situation.

[Animal models in bacterial biofilm research: a review].

Biofilm formation is closely related to pathogenicity and antibiotic resistance of bacteria, and plays important roles in a number of chronic and subchronic infections. Animal models are widely used in the research of bacterial biofilm-associated infections, and provide a powerful scientific tool for investigating its pathogenesis and control strategies. This review summarized the application of mammalian models (e.g. mouse, rabbit, and pig) and non-mammalian models (e.g. Drosophila melanogaster, Zebrafish, and Caenorhabditis elegans) in bacterial biofilm studies, and prospects the application of animal models in biofilm. This review may facilitate the selection of suitable animal models in the study of biofilm-associated infections, so as to prevent and control the potential adverse effects.