Characterization of a broad-spectrum endolysin rLysJNwz and its utility against Salmonella in foods.

Salmonella is a common foodborne pathogen worldwide. The use of bacteriophage-encoded endolysins as antimicrobial agents is a promising approach for controlling pathogenic contamination. In this context, a recombinant endolysin named rLysJNwz, consisting of a single domain falling with the L-alanogyl-D-glutamate peptidase-like family, was cloned, expressed, and characterized. The yield of rLysJNwz was about 25 mg/L. Synergy between 7.5 µg/mL rLysJNwz and 0.5 mmol/L EDTA could decrease the viable counts of Salmonella NCTC 8271 by 93.28%. A synergistic effect between rLysJNwz and polymyxin B was demonstrated, exhibiting the MIC of polymyxin B decreased by twofold. Specifically, rlysJNwz had strong thermostability at temperatures (4-95 °C) and maintained high activity at pHs from 5.0 to 11.0. rlysJNwz was a metal ion-dependent peptidase, which activated by divalent metal ions such as Zn2+, Mn2+, or Ca2+. Moreover, it was also found that the synergism of rlysJNwz and EDTA had bactericidal activities against a broad range of Gram-negative bacteria, including several multidrug-resistant bacteria. The application of rLysJNwz combined with EDTA was evaluated on contaminated eggs and lettuce for 60 min, displaying more than 86.7% and 86.5% reduction of viable Salmonella, respectively. Hence, these results suggest that rLysJNwz is a potential antibacterial agent to control Salmonella, especially antibiotic-resistant pathogen contamination in the field of food safety. KEY POINTS: • rLysJNwz shows lytic activities against a broad range of Gram-negative bacteria. • Endolysin rLysJNwz is a stable metalloenzyme and has high thermostability. • rLysJNwz and 0.5 mmol/L EDTA synergistically inactivate Salmonella on eggs and lettuce.

All-fiber laser feedback interferometer using a DBR fiber laser for effective sub-picometer displacement measurement.

A fiber autodyne laser feedback displacement sensor based on the effect of the frequency shift is demonstrated. The all-fiber structure enables our system to be easily employed in diverse complex and narrow scenes. By virtue of adopting an ultra-high sensitivity distributed Bragg reflector (DBR) fiber laser as the laser source and the frequency-shift technology to avoid the phenomenon that the measured signal of the low frequency is submerged in the noise, the measurement of the sub-picometer displacement under weak feedback condition has been achieved, which shows a great potential in the field of micro-vibration measurement. Moreover, the proposed system has advantages such as simplicity in system structure, low cost of implementation, and immunity to electromagnetic interference.

Coherent laser detection of the femtowatt-level frequency-shifted optical feedback based on a DFB fiber laser.

The theoretical basis and experimental realization of an all-fiber self-mixing laser Doppler velocimetry based on frequency-shifted feedback in a distributed feedback (DFB) fiber laser are presented, which employs a pair of fiber-coupled acousto-optic modulators to adjust the modulation intensity and frequency of the laser self-mixing effect. Moreover, the minimum optical feedback intensity for the velocity signal successfully measured by the interferometer is 5.12 fW, corresponding to 0.16 photons per Doppler cycle. The results demonstrate that the proposed scheme can adapt to the non-contact measurement requirements of the wide-range speed and weak feedback level in the complex environment.

Optical feedback interferometry with 40 km transmission distance based on a distributed feedback fiber laser.

This Letter proposes an all-fiber self-mixing interferometric method based on laser feedback technology with long transmission distance, which has advantages of high sensitivity and compact structure. We theoretically and experimentally verify that the measurement distance of the self-mixing sensor is not limited to the coherence length of the solitary laser used. In the experiment, the velocity of a non-cooperative target was successfully measured with 40 km transmission distance. Therefore, the all-fiber self-mixing Doppler velocimeter has a great application prospect in the field of remote sensing measurement. Its unique flexibility can be applied to a variety of complex environments of non-cooperative target measurement.

Relaxation characteristics for efficient fluorescence lifetime detection of gain media in the fiber laser.

By using different active materials as gain media, we demonstrate a system aimed to measure the fluorescence lifetime of gain media in the fiber laser by utilizing the correlation between the laser's relaxation oscillation characteristics and the fluorescence lifetime of the active materials. As the advantages of extremely compact configuration, non-destructive and real time of the system, the fluorescence lifetime of gain media composed of materials of erbium-ytterbium-doped or erbium-doped have been measured, whose results are 20.2 µs and 1.62 ms, respectively. The proposed method provides a new, to the best of our knowledge, idea for real-time monitoring of fluorescence lifetime in the fiber laser.

All-fiber self-mixing laser Doppler velocimetry with much less than 0.1 pW optical feedback based on adjustable gain.

The all-fiber self-mixing laser Doppler velocimetry with adjustable gain is experimentally investigated based on a distributed Bragg reflector fiber laser. In the measurement system, the modulation gain of the injected light in the laser cavity is adjusted by a pair of fiber-coupled acousto-optic modulators (AOMs) in the external cavity, which can change the intensity and frequency of the self-mixing modulation effect. Simultaneously, the minimum feedback intensity from the target to the laser for successful measurements is 0.063 pW. Thus, the all-fiber laser velocimetry can adapt to the detection of ultraweak optical feedback and wide-range velocity measurements in various complex scenes.

Treatment of rats with Jiangzhi Capsule improves liquid fructose-induced fatty liver: modulation of hepatic expression of SREBP-1c and DGAT-2.

BACKGROUND: Jiangzhi Capsule is an Australian listed patented traditional Chinese medicine and has been used for management of lipid abnormalities over the past 10 years. To obtain a better understanding regarding Jiangzhi Capsule, the present study investigated the effects and underlying mechanisms of Jiangzhi Capsule on chronic fructose overconsumption-induced lipid abnormalities. METHODS: Male rats were treated with liquid fructose in their drinking water over 14 weeks. Jiangzhi Capsule was co-administered (once daily, by oral gavage) during the last 7 weeks. Indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by real-time PCR, Western blot and/or immunohistochemistry. RESULTS: Treatment with Jiangzhi Capsule (100 mg/kg) attenuated fructose-induced excessive triglyceride accumulation and Oil Red O-stained area in the liver. This effect was accompanied by amelioration of hyperinsulinemia. There was no significant difference in intakes of fructose and chow, and body weight between fructose control and fructose Jiangzhi Capsule-treated groups. Mechanistically, Jiangzhi Capsule downregulated fructose-stimulated hepatic overexpression of sterol regulatory element binding protein (SREBP)-1/1c at the mRNA and protein levels. Accordingly, the SREBP-1c downstream genes, acetyl-CoA carboxylase-1 and stearoyl-CoA desaturase-1, were also inhibited. In addition, acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver was also inhibited after Jiangzhi Capsule treatment. In contrast, Jiangzhi Capsule affected neither carbohydrate response element binding protein, peroxisome proliferator-activated receptor (PPAR)-gamma and DGAT-1, nor PPAR-alpha and its target genes. CONCLUSIONS: These findings demonstrate the anti-steatotic action of Jiangzhi Capsule in fructose-fed rats, and modulation of hepatic SREBP-1c and DGAT-2 involved in hepatic de novo synthesis of fatty acids and triglyceride, respectively. Our findings provide an evidence-based and mechanistic understanding of Jiangzhi Capsule supporting its application for the prevention and/or treatment of fatty liver and its associated disorders in clinical practice.

Phage-driven coevolution reveals trade-off between antibiotic and phage resistance in Salmonella anatum.

Phage therapy faces challenges against multidrug-resistant (MDR) Salmonella due to rapid phage-resistant mutant emergence. Understanding the intricate interplay between antibiotics and phages is essential for shaping Salmonella evolution and advancing phage therapy. In this study, MDR Salmonella anatum (S. anatum) 2089b coevolved with phage JNwz02 for 30 passages (60 days), then the effect of coevolution on the trade-off between phage and antibiotic resistance in bacteria was investigated. Our results demonstrated antagonistic coevolution between bacteria and phages, transitioning from arms race dynamics (ARD) to fluctuating selection dynamics (FSD). The fitness cost of phage resistance, manifested as reduced competitiveness, was observed. Bacteria evolved phage resistance while simultaneously regaining sensitivity to amoxicillin, ampicillin, and gentamicin, influenced by phage selection pressure and bacterial competitiveness. Moreover, the impact of phage selection pressure on the trade-off between antibiotic and phage resistance was more pronounced in the ARD stage than in the FSD stage. Whole genome analysis revealed mutations in the btuB gene in evolved S. anatum strains, with a notably higher mutation frequency in the ARD stage compared to the FSD stage. Subsequent knockout experiments confirmed BtuB as a receptor for phage JNwz02, and the deletion of btuB resulted in reduced bacterial competitiveness. Additionally, the mutations identified in the phage-resistant strains were linked to multiple single nucleotide polymorphisms (SNPs) associated with membrane components. This correlation implies a potential role of these SNPs in reinstating antibiotic susceptibility. These findings significantly advance our understanding of phage-host interactions and the impact of bacterial adaptations on antibiotic resistance.

The clinical significance and function of EGFR mutation in TKI treatments of NSCLC patients.

BACKGROUND: EGFR mutations widely exists in NSCLC patients, which are involved in cancer development. OBJECTIVE: The function of EGFR mutations in the resistance to TKI treatments of NSCLC was evaluated to provide theoretical support for the clinical management of NSCLC patients. METHODS: A total of 150 NSCLC patients including 118 patients with EGFR mutation and 32 without, were included in this study. The EGFR mutation status and subtypes were analyzed in recruited patients. The distribution of EGFR mutation subtypes and their association with clinicopathological features were also assessed. The prognostic value of EGFR mutation was evaluated by the overall survival of recruited patients. The function of EGFR mutation was estimated, in vitro, in the TKI resistant NSCLC cells with different subtypes of EGFR mutation. RESULTS: The exon 19 deletion was the most common subtype of EGFR mutation in the enrolled patients followed by the exon 21 L858R point mutation. The EGFR mutations were closely associated with the differentiation degree and the histological types of NSCLC cases. EGFR mutation was an independent prognostic factor of NSCLC with a close relationship with the overall survival of patients. The exon 20 T790M mutation results in the erlotinib resistance through the PI3K/Akt signaling pathway. CONCLUSIONS: The EGFR mutation is a critical factor in the prognosis and for the resistance to TKI treatment in NSCLC. The exon 20 T790M mutation was involved in the erlotinib resistance through PI3K/Akt signaling pathway.

A Web-Based Prediction Model for Cancer-Specific Survival of Elderly Patients With Hypopharyngeal Squamous Cell Carcinomas: A Population-Based Study.

Background: Hypopharyngeal squamous cell carcinomas (HPSCC) is one of the causes of death in elderly patients, an accurate prediction of survival can effectively improve the prognosis of patients. However, there is no accurate assessment of the survival prognosis of elderly patients with HPSCC. The purpose of this study is to establish a nomogram to predict the cancer-specific survival (CSS) of elderly patients with HPSCC. Methods: The clinicopathological data of all patients from 2004 to 2018 were downloaded from the SEER database. These patients were randomly divided into a training set (70%) and a validation set (30%). The univariate and multivariate Cox regression analysis confirmed independent risk factors for the prognosis of elderly patients with HPSCC. A new nomogram was constructed to predict 1-, 3-, and 5-year CSS in elderly patients with HPSCC. Then used the consistency index (C-index), the calibration curve, and the area under the receiver operating curve (AUC) to evaluate the accuracy and discrimination of the prediction model. Decision curve analysis (DCA) was used to assess the clinical value of the model. Results: A total of 3,172 patients were included in the study, and they were randomly divided into a training set (N = 2,219) and a validation set (N = 953). Univariate and multivariate analysis suggested that age, T stage, N stage, M stage, tumor size, surgery, radiotherapy, chemotherapy, and marriage were independent risk factors for patient prognosis. These nine variables are included in the nomogram to predict the CSS of patients. The C-index for the training set and validation was 0.713 (95% CI, 0.697-0.729) and 0.703 (95% CI, 0.678-0.729), respectively. The AUC results of the training and validation set indicate that this nomogram has good accuracy. The calibration curve indicates that the observed and predicted values are highly consistent. DCA indicated that the nomogram has a better clinical application value than the traditional TNM staging system. Conclusion: This study identified risk factors for survival in elderly patients with HPSCC. We found that age, T stage, N stage, M stage, tumor size, surgery, radiotherapy, chemotherapy, and marriage are independent prognostic factors. A new nomogram for predicting the CSS of elderly HPSCC patients was established. This model has good clinical application value and can help patients and doctors make clinical decisions.

Significant Benefits of Afatinib and Apatinib in a Refractory Advanced NSCLC Patient Resistant to Osimertinib: A Case Report.

EGFR-tyrosine kinase inhibitors (TKIs) have revolutionized the treatment for NSCLC. However, acquired drug resistance often occurs after treatment with EGFR-TKIs. EGFR T790M and C797S mutations are the most common resistance mechanism in patients who failed from first- and third- generation EGFR TKI treatments, respectively. However, there is no standard of care for NSCLC harboring EGFR T790M and C797S in-cis. The present case reports a 69-year-old Chinese man with advanced NSCLC harboring EGFR exon 19-deletion, T790M, cis-C797S, and HER2 amplification who was heavily pre-treated. The patient was then given a combination of afatinib and apatinib and achieved a PFS of more than 10 months. This case showed that afatinib plus apatinib may be a promising therapy for patients with EGFR 19Del-T790M-cis-C797S mutant and HER2 amplified NSCLC.

Comparison of the Prognostic Value of Systemic Inflammation Response Markers in Small Cell Lung Cancer Patients.

Increasing evidences support that systemic inflammation-based prognostic scores, modified Glasgow Prognostic Score (mGPS), C-reactive Protein/Albumin (CRP/ALB), Albumin/Globulin (AGR), Prognostic Nutritional Index (PNI) and Advanced Lung cancer Inflammation index (ALI), are key determinants of patients' outcome in solid tumors. However, in small cell lung cancer (SCLC), there have been no direct comparisons of them. Thus, the aim of this study was to compare the prognostic value of these markers in SCLC, and select a most appropriative one. The patients with confirmed SCLC were screened between 2006 and 2011, and inflammation-based prognostic factors (mGPS, CRP/ALB, AGR, PNI, ALI) were examined. Kaplan-Meier and Cox regression analysis were performed to assess these inflammation-based prognostic scores associated with overall survival (OS). Subsequently, we compared the prognostic value of these inflammation-based prognostic scores using the area under the curve (AUC). In 451 patients, on univariate analysis, mGPS (P<0.001), CRP/ALB (P<0.001), AGR (P<0.001), PNI (P<0.001) and ALI (P<0.001) were the strongest predictors of OS. Further multivariate analysis confirmed mGPS (P<0.001), CRP/ALB (P=0.007), AGR (P=0.034) and PNI (P=0.026) as independent markers associated with OS. Further subgroup analysis revealed CRP/ALB was able to predict outcome in both limited (P=0.005) and extensive disease (P=0.013). The CRP/ALB had higher AUC values compared with other inflammation-based prognostic socres (0.566). The CRP/ALB was characterized as best, in comparison to other systemic inflammation-based prognostic scores, for its predictive power of SCLC patients' survival, and had the potential to be hierarchical factor in future clinical trials.