Geographical verification of Pleuropterus multiflorus thunb. by functional compounds, stable isotope ratios, and multielement combined with machine learning methods.

The dry roots of Pleuropterus multiflorus Thunb. (PM) have been traditionally utilized as functional foods and medicines China and various Asian countries. They are extensively cultivated in multiple provinces in China, with variations in prices and qualities. This study aims to investigate the regional characteristics of PM by 4 stable isotope ratios, 40 multielement and 16 functional compounds contents, using a total of 357 samples from 8 different geographical origins. Machine learning methods were developed to authenticating the geographical origins of PM, yielding the accuracy range from 94.44 % to 100 % in the test set. Notably, the protected designation of origin, Deqing PM, exhibited a high accuracy of 100 % in most models, A total of 30 significant prediction variables, encompassing 16 functional compounds, δ2H, 12 rare earth elements, and Cu, were identified. Additionally, the study identified altitude, high temperature, and dry or moisture index as the primary influenced environmental factors.

[Rapid detection technology of chemical component content in Lycii Fructus based on hyperspectral technology].

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The Battlefield of Chemotherapy in Pediatric Cancers.

The survival rate for pediatric cancers has remarkably improved in recent years. Conventional chemotherapy plays a crucial role in treating pediatric cancers, especially in low- and middle-income countries where access to advanced treatments may be limited. The Food and Drug Administration (FDA) approved chemotherapy drugs that can be used in children have expanded, but patients still face numerous side effects from the treatment. In addition, multidrug resistance (MDR) continues to pose a major challenge in improving the survival rates for a significant number of patients. This review focuses on the severe side effects of pediatric chemotherapy, including doxorubicin-induced cardiotoxicity (DIC) and vincristine-induced peripheral neuropathy (VIPN). We also delve into the mechanisms of MDR in chemotherapy to the improve survival and reduce the toxicity of treatment. Additionally, the review focuses on various drug transporters found in common types of pediatric tumors, which could offer different therapeutic options.

Application of hyperspectral imaging assisted with integrated deep learning approaches in identifying geographical origins and predicting nutrient contents of Coix seeds.

Coix seed (CS, Coix lachryma-jobi L. var. ma-yuen (Roman.) Stapf) has rich nutrients, including starch, protein and oil. The geographical origin with a protected geographical indication and high levels of nutrient contents ensures the quality of CS, but non-destructive and rapid methods for predicting these quality indicators remain to be explored. This paper proposed hyperspectral imaging (HSI) assisted with the integrated deep learning models of attention mechanism (AM), convolutional neural networks, and long short-term memory. The method achieved the effective wavelengths selection, the highest prediction accuracy for production region discrimination and the lowest mean absolute error and root mean squared error for nutrient contents prediction. Moreover, the wavelengths selected via the AM model were explicable and reliable for predicting the geographical origins and nutrient contents. The proposed combination of HSI with integrated deep learning models has great potential in the quality evaluation of CS.

Metabolites and chemometric study of Perilla (Perilla frutescens) from different varieties and geographical origins.

Perilla (Perilla frutescens, PF) is an annual labiaceae herb that can be used as vegetable, seasoner, and herb, which mainly includes red PF (P. frutescens var. crispa) and green PF (P. frutescens var. frutescens). Red and green Perilla is mainly used for medicine and food, respectively. In order to explore the differences between these two Perilla cultivars and the effects of origin on them, we studied the components of 130 Perilla samples from different origins by ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry combined with partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis. In this study, 57 potential compounds were analyzed, mainly including organic acids, flavonoids, terpenoids, and anthocyanins. In different varieties of Perilla, anthocyanins were found only in red PF. In addition, the content of four flavonoids, two organic acids, and one coumarin in red PF is much higher than that in green PF. Among the same variety of Perilla, the contents of three metabolites were higher in the north of China for red Perilla, while five metabolites were higher in the south of China for green Perilla. Overall, this research provided a basis for distinguishing different varieties and sources of Perilla through the differential metabolites of Perilla.

The AP2 transcription factors TOE1/TOE2 convey Arabidopsis age information to ethylene signaling in plant de novo root regeneration.

MAIN CONCLUSION: We reveal that transcription factors TOE1 and TOE2 directly inhibit the transcription of EIN3. Ethylene triggers leaf abscission and senescence during plant aging. Previous studies have shown that the transcription of ETHYLENE INSENSITIVE 3 (EIN3), which encodes a key transcription factor in ethylene signaling, is gradually upregulated during plant aging. However, it is still unknown how plants transmit their age information to achieve transcriptional control of EIN3. Here, we report that the EAR-like motif-containing transcription factors TARGET OF EAT 1 (TOE1) and its homolog TOE2 directly associated with the EIN3 promoter. The transcription of EIN3 is further enhanced in mutants of toe1 toe2 during plant aging. TOE1/TOE2 are tightly controlled by canonical microRNA 172 (miR172)-mediated plant aging signaling, which result in a decline in TOE1/TOE2 expression during aging. These results illustrate that during plant aging, the reduced expressions of TOE1/TOE2 trigger an upregulation of EIN3. Next, we took advantage of EIN3-regulated de novo root regeneration (DNRR) as an age-controlled phenotype to dissect the biological function of this regulatory circuit. The DNRR rates in toe1 toe2 are more severely decreased with plant aging; however, the simultaneous loss of ein3 and eil1 (toe1 toe2 ein3 eil1 quadruple mutants) almost completely rescued the DNRR defects. Taken together, our findings show that the plant age-regulated TOE transcription factors precisely integrate plant age information and developmental programs through direct protein-DNA interactions.

Nutrient content prediction and geographical origin identification of red raspberry fruits by combining hyperspectral imaging with chemometrics.

The geographical origin and the important nutrient contents greatly affect the quality of red raspberry (RRB, Rubus idaeus L.), a popular fruit with various health benefits. In this study, a chemometrics-assisted hyperspectral imaging (HSI) method was developed for predicting the nutrient contents, including pectin polysaccharides (PPS), reducing sugars (RS), total flavonoids (TF) and total phenolics (TP), and identifying the geographical origin of RRB fruits. The results showed that these nutrient contents in RRB fruits had significant differences between regions (P < 0.05) and could be well predicted based on the HSI full or effective wavelengths selected through competitive adaptive reweighted sampling (CARS) and variable iterative space shrinkage approach (VISSA). The best prediction results of PPS, RS, TF, and TP contents were achieved with the highest residual predictive deviation (RPD) values of 3.66, 3.95, 2.85, and 4.85, respectively. The RRB fruits from multi-regions in China were effectively distinguished by using the first derivative-partial least squares discriminant analysis (DER-PLSDA) model, with an accuracy of above 97%. Meanwhile, the fruits from three protected geographical indication (PGI) regions were successfully classified by using the orthogonal partial least squares discrimination analysis (OPLSDA) model, with an accuracy of above 98%. The study results indicate that HSI assisted with chemometrics is a promising method for predicting the important nutrient contents and identifying the geographical origin of red raspberry fruits.

Research on the proximity functions of microdosimetry of low energy electrons in liquid water based on different Monte Carlo codes.

PURPOSE: The proximity function is an important index in microdosimetry for describing the spatial distribution of energy, which is closely related to the biological effects of organs or tissues in the target area. In this work, the impact of parameters, such as physic models, cut-off energy, and initial energy, on the proximity function are quantitated and compared. METHODS: According to the track structure (TS) and condensed history (CH) low-energy electromagnetic models, this paper chooses a variety of Monte Carlo (Monte Carlo, MC) codes (Geant4-DNA, PHITS, and Penelope) to simulate the track structure of low-energy electrons in liquid water and evaluates the influence of the electron initial energy, cut-off energy, energy spectrum, and physical model factors on the differential proximity function. RESULTS: The results show that the initial energy of electrons in the low-energy part (especially less than 1 keV) has a greater impact on the differential proximity function, and the choice of cut-off energy has a greater impact on the differential proximity function corresponding to small radius sites (generally less than 10 nm). The difference in the electronic energy spectrum has little effect on the result, and the proximity functions of different physics models show better consistency under large radius sites. CONCLUSIONS: This work comprehensively compares the differential proximity functions under different codes by setting a variety of simulation conditions and has basic guiding significance for helping users simulate and analyze the deposition characteristics of microscale electrons according to the selection of an appropriate methodology and cut-off energy.

Transporter NRT1.5/NPF7.3 suppresses primary root growth under low K+ stress by regulating the degradation of PIN-FORMED2.

BACKGROUND: The availability of potassium is one of the main environmental factors for modifying the plasticity of root architecture. Many potassium channels and transporters are involved in regulating primary root growth in response to low potassium stress. NRT1.5/NPF7.3 transporter is a NO3-/H+ and K+/H+ cotransporter, and participates in NO3- and K+ translocation from the roots to the shoots. However, the underlying mechanism of NRT1.5-regulated primary root growth under low potassium stress is unclear. RESULTS: We show that NRT1.5/NPF7.3 inhibited primary root growth under low potassium conditions by regulating the accumulation of PIN2 protein and auxin levels. Under low potassium conditions, the mutants nrt1.5 and lks2 exhibited longer primary roots, longer meristem regions and elongation zones of primary roots, and more cell activity in the meristem region compared to WT plants, revealing the involvement of NRT1.5 in LK (low potassium)-inhibition primary root growth. In addition, exogenous auxin (IAA), auxin analogue (NAA, 2.4-D) or auxin precursor (IBA) promoted the primary root growth of WT and the complementation line NRT1.5 COM plants. In addition, the application of NPA inhibited the primary root growth of the nrt1.5 and lks2 mutants. Auxin accumulation was higher in the root tip of nrt1.5 plants than in WT plants, indicating that NRT1.5 regulates root growth inhibition by regulating auxin distribution. Furthermore, PIN2 was degraded more quickly in nrt1.5 plants under LK stress. CONCLUSIONS: Our findings reveal that NRT1.5 inhibits primary root growth by modulating the auxin level in the root tip via the degradation of PIN2.

An inner filter effect-based nitrogen-doped carbon dots-CoOOH nanoflakes fluorescence probe for detection of ascorbic acid by chemical redox modulation.

BACKGROUND: Ascorbic acid (AA) is an essential nutrient for humans, which must be obtained from vegetables, fruits, and other foods. The content of AA has become an important standard to evaluate the quality and nutritional value of food. The fluorescence sensing method based on nanomaterials is a good alternative for the rapid detection of AA. In this study, we developed an inner filter effect-based fluorescent probe that hybridized nitrogen-doped carbon dots (NCDs) with cobalt oxyhydroxide nanoflakes (CoOOH NFs). RESULTS: An optimal NCDs was successfully selected because it has a strong fluorescence at 430 nm and the most significant quenching phenomenon with CoOOH NFs due to the inner filter effect. When adding AA into the NCDs-CoOOH NFs probe solution, a specific redox reaction will occur between the enediol group of AA and the CoOOH NFs to interfere with the quenching ability of CoOOH NFs and recover the fluorescence of NCDs. The recovered fluorescence intensities demonstrated a linear relationship with the concentrations of AA. The assay based on the NCDs-CoOOH NFs probe allows AA to be tested in a wide range of 5-200 µmol L-1 with a detection limit of 2.31 nmol L-1 . Furthermore, to evaluate its practical application, the NCDs-CoOOH NFs fluorescence probe was utilized to analyze AA in vegetable, fruit, and serum matrixes with satisfactory results. CONCLUSION: An inner filter effect-based fluorescence probe for the rapid detection of AA was developed, and it has a good potential to be applied in both food and clinical testing. © 2022 Society of Chemical Industry.

Relationship between miR-338-3p and Clinicopathological Parameters, Prognosis, and STAT3 mRNA Expression in Nasopharyngeal Carcinoma.

OBJECTIVE: To investigate the expression of miR-338-3p in nasopharyngeal carcinoma (NPC) and its relationship with STAT3 mRNA expression as well as their relationship with clinical pathological parameters and prognosis of patients. METHODS: From September 2016 to September 2018, 71 patients with NPC were selected as the NPC group, and 71 samples of NPC tissues were collected during the operation. A total of 23 patients who underwent biopsy due to chronic nasopharyngitis were selected as the control group and 23 nasopharyngeal mucosal tissues were collected. The expressions of miR-338-3p and STAT3 mRNA in nasopharyngeal tissue of two groups were detected by real-time quantitative PCR, and the relationship between the two was analyzed. To collect clinical data of NPC patients and analyze the relationship between the expressions of miR-338-3p and STAT3 in NPC tissues and clinical pathological parameters of the patients, we followed up the patients with nasopharyngeal carcinoma for three years to observe the relationship between miR-338-3p, STAT3, and the prognosis of the patients. RESULTS: The relative expression levels of miR-338-3p in nasopharyngeal tissues of the NPC group and the control group were 0.39 ± 0.05 and 1.01 ± 0.09, respectively (P < 0.05). The relative expression levels of STAT3 mRNA in nasopharyngeal tissues of the NPC group and the control group were 3.82 ± 0.21 and 1.04 ± 0.11, respectively (P > 0.05). miR-338-3p was negatively correlated with the relative expression of STAT3 mRNA in nasopharyngeal carcinoma (r = 0.038, P > 0.05). The expression of miR-338-3p was related to the age of the patient, clinical TNM stage, T stage, and distant metastasis (all P < 0.05). STAT3 expression was correlated with clinical TNM stage, T stage, and distant metastasis in our patient (P < 0.05). The expressions of miR-338-3p and STAT3 in nasopharyngeal carcinoma tissues from different gender, histological type, N stage, M stage, and degree of differentiation showed no statistical differences (P > 0.05). The survival rate of the group with low miR-338-3p expression was significantly lower than that of the group with high miR-338-3p expression (P > 0.05). The survival rate of patients with the high STAT3 expression group was significantly lower than that of patients with the low STAT3 expression group (P > 0.05). CONCLUSION: There is a negative correlation between the low expression of miR-338-3p and the high expression of STAT3 in NPC, which are all related to the TNM stage, T stage, and prognosis of the patient.

Characterization of CD66b and its relationship between immune checkpoints and their synergistic impact in the prognosis of surgically resected lung adenocarcinoma.

OBJECTIVES: CD66b positive tumor-infiltrating neutrophils (TINs) are key immunity cells in the tumor microenvironment (TME). However, their relationship with clinicopathological features, immune checkpoints (ICs), and prognostic value remains undetermined in lung adenocarcinoma (LUAD). In this study, we aimed to characterize the infiltration by TINs and the prognostic significance in patients with surgically resected LUAD. MATERIALS AND METHODS: Expression of CD66b and ICs, including PD-L1, PD-1, CTLA4, LAG3, TIM3, TIGIT, VISTA, and BTLA, in both cancer cell and tumor-infiltrating lymphocytes (TILs) were estimated by immunohistochemistry in resected LUAD. The associations between CD66b expression and clinicopathological characteristics in patient prognoses were analyzed. We also verified results in another cohort from 85 patients with untreated LUAD and further analyzed the correlation between CD66b expression and EGFR and KRAS mutation status in addition to the rearrangement of the anaplastic lymphoma receptor tyrosine kinase gene (ALK). RESULTS: A total of 240 patients were included in this study. CD66b expression was observed in 87 (36.2%) samples. ICs including PD-L1, PD-1, CTLA4, LAG3, TIM3, TIGIT, VISTA, and BTLA were observed in percentages that ranged from 23.8% to 59.4%. Positive CD66b expression significantly correlated with smoking history (p = 0.029), pathological stage (p = 0.040), and the positive expression of LAG-3 (p < 0.001), PD-1 (p = 0.008), CTLA-4 (p = 0.013), TIM-3 (p = 0.025), TIGIT (p = 0.002), PD-L1 in TILs (p = 0.015), and PD-L1 in tumor cells (p = 0.010). CD66b positivity was significantly associated with worse recurrence-free survival (RFS) (hazard ratio, HR, 1.687; 95% confidence interval, CI, 1.058-2.690, p = 0.028) and overall survival (OS) (HR, 1.667; 95% CI, 1.097-2.534, p = 0.017). Subgroup analysis revealed that the CD66b+/LAG-3 + group had the worst RFS (5-year rate: 39.5%,) and OS (5-year rate: 53.7%,), while the CD66b-/LAG-3 - group had the best RFS (5-year rate: 65.6%) and OS (5-year rate: 78.8%). The p value in analysis of RFS and OS was 0.005 and 0.008, respectively. In the verification set, high expression of CD66b was also significantly correlated with the positive expression of LAG-3 (p < 0.001), PD-1 (p = 0.002), CTLA-4 (p = 0.034), TIM-3 (p = 0.049), PD-L1 in TILs (p = 0.003), and PD-L1 in tumor cells (p = 0.045). There was no correlation between CD66b expression and positive TIGIT expression (p = 0.077), EGFR mutation (p = 0.223), KRAS mutation (p = 0.151), and ALK fusion (p = 0.310). CONCLUSION: CD66b had a relatively high positive expression rate and special clinicopathological features in patients with LUAD. CD66b + TINs were related to the expression of ICs and associated with poor prognoses in LUAD. A combination of CD66b and ICs, especially LAG-3 could further stratify patients into different groups with distinct prognoses.

Saffron (Crocus sativus L.) and health outcomes: a meta-research review of meta-analyses and an evidence mapping study.

BACKGROUND: Although a number of systematic reviews and meta-analyses of saffron (Crocus sativus L.) have been published, no study has comprehensively summarized the clinical evidence from meta-analyses, or assessed the reporting or methodological quality of these reviews. PURPOSE: The present meta-research study was designed to fill the gaps in knowledge to inform future studies and allow enhanced clinical decision-making on saffron. METHODS: The PubMed, Cochrane Library, Embase, and CNKI databases were systematically searched from inception to April 3 rd, 2021, for meta-analyses of clinical trials that assessed the efficacy and safety of saffron. PRISMA 2009 and AMSTAR-2 were employed to assess the reporting and methodological quality of meta-analyses identified in the search, respectively. The present study was registered on PROSPERO with registration number CRD42020220274. RESULTS: Nineteen eligible systematic reviews with meta-analyses published in English were identified from 235 records. These meta-analyses were published in 12 peer-reviewed journals from 2013 to 2021. The heterogeneous results indicated that saffron significantly reduced fasting blood glucose, waist circumference, diastolic blood pressure, concentrations of total cholesterol and low-density lipoprotein cholesterol, and improved symptoms of depression, cognitive function and sexual dysfunction compared with controls (mainly placebos). Common side effects of saffron consumption included nausea, dry mouth, poor appetite, and headache, but no serious adverse reactions were reported. Primary analysis and sensitivity analysis confirmed that the reporting and methodological quality of reviews included in the study were highly correlated (p < 0.001). The quality of meta-analyses of saffron requires improvement by including a structured abstract, a prospective protocol and registration, explanation of the study designs within each study that is reviewed, the searches, risk of bias assessment, literature selection, and reporting of funding sources. CONCLUSION: The available evidence indicates that saffron is a safe plant for administration as a medicine and can improve diverse clinical outcomes, but the scientific quality of the published systematic reviews needs to be improved. Moreover, the clinical effects of saffron need to be confirmed through high-quality randomized trials in multiple countries with large sample sizes.

Spider-Web and Ant-Tentacle Doubly Bio-Inspired Multifunctional Self-Powered Electronic Skin with Hierarchical Nanostructure.

For the practical applications of wearable electronic skin (e-skin), the multifunctional, self-powered, biodegradable, biocompatible, and breathable materials are needed to be assessed and tailored simultaneously. Integration of these features in flexible e-skin is highly desirable; however, it is challenging to construct an e-skin to meet the requirements of practical applications. Herein, a bio-inspired multifunctional e-skin with a multilayer nanostructure based on spider web and ant tentacle is constructed, which can collect biological energy through a triboelectric nanogenerator for the simultaneous detection of pressure, humidity, and temperature. Owing to the poly(vinyl alcohol)/poly(vinylidene fluoride) nanofibers spider web structure, internal bead-chain structure, and the collagen aggregate nanofibers based positive friction material, e-skin exhibits the highest pressure sensitivity (0.48 V kPa-1 ) and high detection range (0-135 kPa). Synchronously, the nanofibers imitating the antennae of ants provide e-skin with short response and recovery time (16 and 25 s, respectively) to a wide humidity range (25-85% RH). The e-skin is demonstrated to exhibit temperature coefficient of resistance (TCR = 0.0075 °C-1 ) in a range of the surrounding temperature (27-55 °C). Moreover, the natural collagen aggregate and the all-nanofibers structure ensure the biodegradability, biocompatibility, and breathability of the e-skin, showing great promise for practicability.

Transplantation of the Stromal Vascular Fraction (SVF) Mitigates Severe Radiation-Induced Skin Injury.

Severe radiation-induced skin injury is a complication of tumor radiotherapy and nuclear accidents. Cell therapy is a potential treatment for radiation-induced skin injury. The stromal vascular fraction (SVF) is a newer material in stem cell therapy that is made up of stem cells harvested from adipose tissue, which has been shown to promote the healing of refractory wounds of different causes. In this study, SVF was isolated from patients with radiation-induced skin injury. Adipose-derived stem cells (ADSCs) accounted for approximately 10% of the SVF by flow cytometry. Compared with the control group of rats, administration with SVF attenuated the skin injury induced by electron beam radiation. The effect of SVF on the human skin fibroblast microenvironment was determined by proteomic profiling of secreted proteins in SVF-co-cultured human skin fibroblast WS1 cells. Results revealed 293 upregulated and 1,481 downregulated proteins in the supernatant of SVF-co-cultured WS1 cells. WS1 co-culture with SVF induced secretion of multiple proteins including collagen and MMP-1. In the clinic, five patients with radiation-induced skin injury were recruited to receive SVF transfer-based therapy, either alone or combined with flap transplantation. Autogenous SVF was isolated and introduced into a multi-needle precision electronic injection device, which automatically and aseptically distributed the SVF to the exact layer of the wound in an accurate amount. After SVF transfer, wound healing clearly improved and pain was significantly relieved. The patients' skin showed satisfactory texture and shape with no further wound recurrence. Our findings suggest that transplantation of SVF could be an effective countermeasure against severe radiation-induced skin injury.

Chinese Medicine as an Adjunctive Treatment for Gastric Cancer: Methodological Investigation of meta-Analyses and Evidence Map.

Background: Many meta-analyses (MAs) on Chinese medicine (CM) as an adjunctive treatment for gastric cancer have been published in recent years. However, the pooled evidence reported in MAs and their methodological quality remain unknown. Therefore, we designed a study to comprehensively evaluate and summarize the current evidence of CMs for gastric cancer in published MAs. Methods: A systematic search on MAs published in English from inception to 1st September 2021 was conducted in PubMed and Embase. The AMSTAR-2 tool was used to evaluate the methodological quality of the included MAs, and the results of the quality assessment were visualized using the evidence mapping method. Stata 17/SE was used for statistical analysis (Registration number: INPLASY202190005). Results: A total of 20 MAs (16 pairwise and 4 network MAs) were included from 118 records. These MAs were published in 14 journals from 2013 to 2021, with the number of patients and trials ranging from 688 to 6,857, and from 10 to 85, respectively. A large number of CMs (e.g., AiDi, FuFangKuShen, and HuaChanSu) in combination with chemotherapy for gastric cancer were identified among the included MAs. According to the pooled results reported in MAs, when compared to chemotherapy alone, CMs in combination with chemotherapy not only improve various outcomes on efficacy (e.g., objective response rate, quality of life) but also reduce various adverse reactions (e.g., leucopenia, nausea and vomiting). Only 2 MAs were low in terms of the overall methodological quality, while the other 18 MAs were all critically low. The methodology was required to be advanced significantly, mainly involving: study protocol and registration, explanation for the inclusion of study design, list of excluded studies with justifications, adequate details of included studies, reporting on funding sources of primary studies, and evaluation of the potential impact of risk of bias. In addition, MAs that received funds support (ß = 2.68; 95%CI: 0.40 to 4.96; p = 0.024) or were published in journals with higher impact factor (ß = 2.81; 95%CI: 0.69 to 4.92; p = 0.012) had a higher score on the overall methodological quality in the univariate analysis, but the results were not statistically significant according to the multivariate analysis. Conclusion: Combining CMs with chemotherapy can potentially improve clinical outcomes and reduce the relevant adverse effects in patients with gastric cancer. However, the methodological quality of relevant MAs requires significant improvement, and the current evidence needs to be validated through multinational trials that are well-designed and have a large sample size.

One Cycle of Concurrent Chemotherapy vs. Two Cycles of Concurrent Chemotherapy With Radiation Therapy in Patients With Limited-Stage Small Cell Lung Cancer.

BACKGROUND: The optimal number of concurrent chemotherapy cycles during thoracic radiotherapy (RT) in patients with limited stage-small cell lung cancer (LS-SCLC) is not well defined. The purpose of this study was to evaluate the impact of the number of concurrent chemotherapy cycles on prognosis of LS-SCLC. MATERIAL AND METHODS: Patients with LS-SCLC treated with concurrent chemo-radiotherapy from May 2008 to December 2020 in our hospital were retrospectively analyzed. The prescribed radiation dose was 60Gy administrated with conventional RT in 30 fractions within 6 weeks. The prognostic role of cycle number of chemotherapy administrated concurrently with RT were analyzed. All patients were followed up at one month after the treatment, then once every three months until two years after the treatment, and every six months thereafter. Propensity score matching (PSM) was performed to reduce confounding factors. The primary endpoint was overall survival (OS). Survival analysis was performed with Kaplan-Meier and multivariate analysis was performed with Cox regression model. RESULTS: Among the 370 patients who received radical radiotherapy, 206 patients received concurrent chemo-radiotherapy and were included for the analysis. Multivariate analysis showed that stage and PCI were independent prognostic factors for OS. The median OS in patients who received one cycle and two cycles of chemotherapy concurrently with RT were 32.9 months and 31.6 months, respectively (P = 0.241). And the median PFS were 20.6 months and 18.4 months, respectively (P = 0.764). After PSM, no statistical differences in OS and PFS were observed between patients who received one cycle and those who received two cycles of concurrent chemotherapy. CONCLUSION: Two cycles of concurrent chemotherapy during RT were not necessarily superior compared to one cycle in LS-SCLC. The optimal cycle number of concurrent chemotherapy during RT needs to be further studied.

Iturin A Extracted From Bacillus subtilis WL-2 Affects Phytophthora infestans via Cell Structure Disruption, Oxidative Stress, and Energy Supply Dysfunction.

Potato late blight, caused by Phytophthora infestans (Mont.) de Bary, represents a great food security threat worldwide and is difficult to control. Recently, Bacillus spp. have been considered biocontrol agents to control many plant diseases. Here, Bacillus subtilis WL-2 was selected as a potent strain against P. infestans mycelium growth, and its functional metabolite was identified as Iturin A via electrospray ionization mass spectrometry (ESI-MS). Analyses using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that Iturin A caused cell membrane disruption and an irregular internal cell structure. In addition, Iturin A triggered oxidative stress reactions similarly to reactive oxygen species (ROS) in P. infestans cells and caused mitochondrial damage, including mitochondrial membrane potential (MMP), mitochondrial respiratory chain complex activity (MRCCA), and ATP production decline. These results highlight that the cell structure disruption, oxidative stress, and energy supply dysfunction induced by Iturin A play an important role in inhibiting P. infestans. Additionally, B. subtilis WL-2 and Iturin A have great potential for inhibiting P. infestans mycelium growth and controlling potato late blight in the future.

Bacillus megaterium WL-3 Lipopeptides Collaborate Against Phytophthora infestans to Control Potato Late Blight and Promote Potato Plant Growth.

Oomycete Phytophthora infestans [(Mont.) de Bary] is the cause of potato late blight, a plant disease which poses a serious threat to our global food security and is responsible for huge economic losses worldwide. Lipopeptides produced by Bacillus species are known to be potent antibacterial compounds against many plant pathogens. In this study, we show that Bacillus megaterium WL-3 has an antagonistic effect against potato late blight. Electrospray ionization mass spectrometry (ESI-MS) revealed that lipopeptides derived from the WL-3 strain contained three subfamilies, surfactin (C13 - C15), Iturin A (C14 - C16), and Fengycin A (C15 - C19). The Iturin A and Fengycin A lipopeptide families were each confirmed to have anti-oomycete effects against P. infestans mycelium growth as well as obvious controlling effects against potato late blight in greenhouse experiments and field assays. Furthermore, Iturin A and Fengycin A were able to promote plant photosynthetic efficiency, plant growth, and potato yield. Most importantly, the combination of Iturin A and Fengycin A (I + F) was superior to individual lipopeptides in controlling potato late blight and in the promotion of plant growth. The results of this study indicate that B. megaterium WL-3 and its lipopeptides are potential candidates for the control of late blight and the promotion of potato plant growth.

Surfactin and fengycin B extracted from Bacillus pumilus W-7 provide protection against potato late blight via distinct and synergistic mechanisms.

Potato late blight caused by Phytophthora infestans is one of the most serious plant diseases worldwide. Cyclic lipopeptides (CLPs) extracted from Bacillus strains exhibit a promising effect in the biocontrol of a variety of phytopathogens. However, the specific inhibitory effects and underlying mechanisms of CLPs against P. infestans are poorly understood. In this study, we showed that Bacillus pumilus W-7 can inhibit the growth of P. infestans mycelium. Two metabolites from W-7, surfactin and fengycin B, were identified using MS/MS. Fengycin B inhibited mycelium growth by inducing mycelium deformations, oxidative damage, and mitochondrial dysfunction. Surfactin induced potato plant defense responses by increasing the expression of the biocontrol genes (pod, pal, and cat) and their enzyme activities (POD, PAL, and CAT). Also, surfactin and fengycin B could exhibit a synergistic inhibitory effect on P. infestans. Taken together, our findings indicate that B. pumilus W-7 and its CLPs are potential environmentally friendly and effective biocontrol agents for the preservation of potato crops. KEY POINTS: • Lipopeptides of surfactin and fengycin B are extracted from Bacillus pumilus W-7. • Fengycin B inhibits Phytophthora infestans mycelium growth in a direct manner. • Surfactin induces potato plant defense responses to control late blight.