Lipopeptide C17 Fengycin B Exhibits a Novel Antifungal Mechanism by Triggering Metacaspase-Dependent Apoptosis in Fusarium oxysporum.

Fusarium wilt is a worldwide soil-borne fungal disease caused by Fusarium oxysporum that causes serious damage to agricultural products. Therefore, preventing and treating fusarium wilt is of great significance. In this study, we purified ten single lipopeptide fengycin components from Bacillus subtilis FAJT-4 and found that C17 fengycin B inhibited the growth of F. oxysporum FJAT-31362. We observed early apoptosis hallmarks, including reactive oxygen species accumulation, mitochondrial dysfunction, and phosphatidylserine externalization in C17 fengycin B-treated F. oxysporum cells. Further data showed that C17 fengycin B induces cell apoptosis in a metacaspase-dependent manner. Importantly, we found that the expression of autophagy-related genes in the TOR signaling pathway was significantly upregulated; simultaneously, the accumulation of acidic autophagy vacuoles in F. oxysporum cell indicated that the autophagy pathway was activated during apoptosis induced by C17 fengycin B. Therefore, this study provides new insights into the antifungal mechanism of fengycin.

Implementation of a Randomized, Placebo-Controlled Trial of Live Attenuated Malaria Sporozoite Vaccines in an Indonesian Military Study Population.

Malaria eradication efforts prioritize safe and efficient vaccination strategies, although none with high-level efficacy against malaria infection are yet available. Among several vaccine candidates, Sanaria® PfSPZ Vaccine and Sanaria PfSPZ-CVac are, respectively, live radiation- and chemo-attenuated sporozoite vaccines designed to prevent infection with Plasmodium falciparum, the leading cause of malaria-related morbidity and mortality. We are conducting a randomized normal saline placebo-controlled trial called IDSPZV1 that will analyze the safety, tolerability, immunogenicity, and efficacy of PfSPZ Vaccine and PfSPZ-CVac administered pre-deployment to malaria-naive Indonesian soldiers assigned to temporary duties in a high malaria transmission area. We describe the manifold challenges of enrolling and immunizing 345 soldier participants at their home base in western Indonesia before their nearly 6,000-km voyage to eastern Indonesia, where they are being monitored for incident P. falciparum and Plasmodium vivax malaria cases during 9 months of exposure. The unique regulatory, ethical, and operational complexities of this trial demonstrate the importance of thorough planning, frequent communication, and close follow-up with stakeholders. Effective engagement with the military community and the ability to adapt to unanticipated events have proven key to the success of this trial.

Lipopeptides from Bacillus velezensis induced apoptosis-like cell death in the pathogenic fungus Fusarium concentricum.

AIMS: Stem rot caused by Fusarium concentricum is a new disease of Paris polyphylla reported by our research group. The present study investigates the growth inhibitory and apoptotic effects of Bacillus velezensis FJAT-54560 lipopeptide against F. concentricum. METHODS AND RESULTS: HPLC preparation and LC-MS analysis results show that the crude lipopeptides secreted by Bacillus velezensis FJAT-54560 isolated from Jasminum sambac consist of C14-17 iturin A, C14 fengycin B, C16 fengycin A/A2, C18 fengycin A, C20 fengycin B2, C21 fengycin A2, C22-23 fengycin A, C12-16 surfactin A, and C15 surfactin A derivatives. The mass ratios (g/g) of iturin, fengycin, and surfactin in lipopeptides are 2.40, 67.51, and 30.08%, respectively. Through inhibition zone and inhibition rate experiments, we found that crude lipopeptides and purified fengycin exhibit strong antifungal activity against F. concentricum, including accumulation of reactive oxygen species, loss of mitochondrial membrane potential, DNA fragmentation, Ca2+ accumulation, chromatin condensation, and phosphatidylserine externalization. Transcriptomic analysis indicates that crude lipopeptide-induced apoptosis in F. concentricum cells may be mediated by apoptosis-inducing factors and apoptosis mediators and can serve as a metacaspase-independent model. CONCLUSION: Lipopeptides from Bacillus velezensis FJAT-54560 can control the pathogenic fungus F. concentricum by inducing apoptosis.

A Pilot Study to Explore the Improvements in Pulmonary and Cognitive Functions With a Kazoo Intervention Among Middle-Aged and Older Adults in a Rural Community.

Dementia is a leading cause of disability and dependence in older adults worldwide. The aim of this pilot study was to explore the effect of using a kazoo instrument to improve pulmonary function and cognitive reserve in middle-aged and older adults in rural areas. This quasi-experimental study was conducted at two community care stations selected using cluster sampling from a rural district in southern Taiwan. We enrolled 85 middle-aged and older adults who were randomly assigned into self-learner and in-class groups. Both groups received a 6-month kazoo program. Cognitive and pulmonary function were compared before and after the intervention between the two groups. Significantly improved pulmonary function with regards to forced vital capacity (p < .05) was found in the self-learner group, and significantly improved maximum expiratory flow 75% (p < .001) was found in both groups. Mini-Mental State Examination scores significantly improved in the self-learner group (p < .01), but there was no significant change in the in-class group. Our results suggest that community care stations could consider implementing wind instrument programs such as a kazoo to enhance pulmonary function and cognitive reserve in middle-aged and older adults residing in rural areas.

The association between SGLT2 inhibitors and new-onset acute coronary syndrome in the elderly: a population-based longitudinal cohort study.

BACKGROUND: Several observational cohorts and meta-analytical studies on humans have shown that users of sodium-glucose cotransporter-2 inhibitors (SGLT2is) have a lower risk for new-onset acute coronary syndrome (ACS) than nonusers. However, some studies, including randomized clinical trials, reported the opposite results. This study aimed to investigate the impacts of a SGLT2i on new-onset ACS in a population. METHODS: We conducted a retrospective population-based cohort study involving 56,356 subjects who received SGLT2i therapy and 112,712 patients who did not receive SGLT2i therapy between May 1, 2016 and December 31, 2019. The outcome was the risk of new-onset ACS. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals for associations between SGLT2i use and ACS risk. RESULTS: A total of 670 and 1408 ACS events occurred in SGLT2i users and nonusers, respectively, during a follow-up of 3.7 years. SGLT2i use was associated with a nonsignificantly lower risk of ACS (adjusted HR 0.95, 95%confidence intervals (CI 0.87-1.04, P = 0.3218). We confirmed the robustness of these results through a propensity score 1:1 matching analysis. The results of the subgroup analysis of the subtype of the SGLT2i treatments were consistent with the main findings. An increased risk for the incidence of ACS in male and older (> 70 years) patients were also found. CONCLUSIONS: In this population-based cohort study, we found that SGLT2i use is associated with a nonsignificantly decreased risk of ACS. No difference in the SGLT2i subtype was observed in subgroup analyses. However, the results of this study indicated an increased risk for the incidence of ACS in male and older (> 70 years) patients.

Sporozoite immunization: innovative translational science to support the fight against malaria.

INTRODUCTION: Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for Plasmodium falciparum (Pf), the deadliest human malaria parasite. AREAS COVERED: Sporozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving >90% efficacy against Pf infection. This review describes >30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of 'sporozoites,' 'malaria,' and 'vaccines.' EXPERT OPINION: First generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers exposed to Pf in Africa, with licensure for these populations possible within 5 years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives.

Outcome analysis of free flap reconstruction for head and neck cancer with intraoperative indocyanine green angiography.

BACKGROUND: Intraoperative indocyanine green (ICG) angiography is used in free flap surgery to evaluate the patency of vessel anastomosis. This study evaluated the outcomes of intraoperative ICG angiography in free flap surgery for head and neck cancer. MATERIALS AND METHODS: This was a retrospective study of free flap reconstruction for head and neck cancer performed between 2015 and 2021. The outcomes analyzed were the total flap failure rate, re-exploration rate, and flap salvage rate. Differences in outcomes were compared in patients treated using intraoperative ICG angiography and those treated without. RESULTS: Of the 520 free flap surgeries in the 486 enrolled patients, 259 cases underwent intraoperative ICG angiography. In this group, there were 10 (3.9%) cases of total flap failure. In the non-ICG group, there were 22 cases (8.4%). There were 35 (13.5%) cases requiring re-exploration in the ICG group and 40 (15.3%) in the non-ICG group. The difference was not statistically significant. The flap salvage rate was 75.8% (25/33) in the ICG group and 51.4% (18/35) in the non-ICG group, which was a significant difference. CONCLUSION: We found that free flap surgery with intraoperative ICG angiography significantly decreased total flap failure rate and significantly increased salvage rate but did not significantly affect the re-exploration rate.

Dynamics of spatial and temporal population structure of Pyricularia oryzae in Taiwan.

BACKGROUND: To gain a better understanding of how Pyricularia oryzae population shifts is important for selecting suitable resistance genes for rice breeding programs. However, the relationships between P. oryzae pathogenic dynamics, geographic distribution, rice varieties, and timeline are not well studied. RESULTS: Resistance genes Piz-5, Pi9(t), Pi12(t), Pi20(t), Pita-2, and Pi11 showed stable resistance to the Taiwan rice blast fungus over 8 years of observations. Furthermore, 1749 rice blast isolates were collected from 2014 to 2021 and categorized into five pathotype clusters based on their correlation analysis between the geographic sources and virulence of Lijiangxintuanheigu monogenic lines. A detailed map of their distributions in Taiwan is presented. Isolates collected from the western region of Taiwan had greater pathotype diversity than those from the east region. Isolates collected from the subtropical region had greater diversity than those from the tropical region. Rice cultivars carrying Pik alleles were highly susceptible to pathotype L4. Cultivars with Piz-t were highly susceptible to pathotype L5, and those with Pish were highly susceptible to pathotype L1. The geographical distribution of each pathotype was distinct, and the population size of each pathotype fluctuated significantly each year. CONCLUSION: The regional mega cultivars significantly impact the evolution of Pyricularia oryzae in Taiwan within the span of 8 years. However, the annual fluctuation of pathotype populations likely correlate to the rising annual temperatures that selected pathotype clusters by their optimal growth temperature. The results will provide useful information for effective disease management, and enable the R-genes to prolong their function in the fields. © 2023 Society of Chemical Industry.

Antifungal activities of Bacillus velezensis FJAT-52631 and its lipopeptides against anthracnose pathogen Colletotrichum acutatum.

This study was aim at investigating antifungal activities of Bacillus velezensis FJAT-52631 and its lipopeptides against Colletotrichum acutatum ex situ and in situ. The results showed that the strain FJAT-52631 and its crude lipopeptides (10 mg/ml) exhibited strong inhibitory effects on growth of C. acutatum FJAT-30256 with an inhibition rate of 75.3% and an inhibition zone diameter of 17.66 mm, respectively. Both the viable bacterial cultures and lipopeptides of FJAT-52631 could delay the onset of loquat anthracnose by 1 day and lower the incidence of loquat anthracnose in situ. The whole cultures of B. velezensis FJAT-52631 displayed a 50% biocontrol efficacy on loquat anthracnose at the fourth day after inoculation, but the crude lipopeptides not. The average lesion diameter of the whole-culture treated group was 5.62 mm, which was smaller than that of control group (6.81 mm). All the three types of lipopeptides including iturin A, fengycin, and surfactin A secreted from the strain FJAT-52631 exhibited antifungal activities. Among them, surfactin A displayed higher antifungal activity at a concentration of 1.25 mg/mL than other two lipopeptides even if at a concentration of 60 mg/mL. Thus, the results indicated that surfactin A produced by FJAT-52631 played a major role in the biocontrol of the loquat anthracnose. Scanning electron microscopy (SEM) observation revealed the structural deformities in the mycelia of C. acutatum. The above results suggested that the antifungal lipopeptides from B. velezensis FJAT-52631 would be potential in biocontrol against anthracnose disease of loquat caused by C. acutatum.

First Report of Green Mold Disease Caused by Penicillium ochrochloron on Medicinal Plant Pseudostellaria heterophylla in China.

Pseudostellaria heterophylla is one of the Chinese herbal medicines with high medicinal and economic values. From 2019 to 2021, postharvest green mold disease was observed with an incidence of 2~5% on the tuberous roots of the harvested P. heterophylla at eight locations in Zherong county, Fujian Province, China. The symptoms were as follows: white mycelial growth on the tuberous roots surface initially, then green mold layers forming, and the tuberous roots decaying finally. To identify the causal agent, a total of 20 symptomatic tuberous roots were collected. Small pieces (5 mm×5 mm) were treated by surface disinfestion with 75% ethanol and 1% NaOCl, then rinsed 3 times with sterile distilled water. These treated pieces were transferred onto potato dextrose agar (PDA) and incubated at 25°C in the dark for 7 days. Twenty pure cultures were obtained by single-spore isolation method. Colonies on PDA medium initially appeared as white mycelium that developed grayish-green conidia with white margins. Mycelium was septate and colorless. Conidiophores were predominantly monoverticillate, occasionally biverticillate. Stipes was long and slender. Phialides were ampulliform to almost cylindrical with collula, 11.25 (7.80-23.50) µm long (n=50). Conidia were smooth walled and pale green, with globose to ellipsoidal shape, 2.75 (2.37-3.27)× 2.47 (2.18-3.13) µm (n=50). Based on these morphological characteristics, the isolates matched the description of the genus Penicillium. Genomic DNAs from two representative isolates (FJAT-32578 and FJAT-32579) were extracted with a fungal genomic DNA extraction kit. The rDNA ITS region and partial ß-tubulin gene (BenA) were amplified using the primers ITS1/ITS4 (White et al. 1990) and Bt2a/Bt2b (Glass and Donaldson 1995), respectively. The sequences of isolate FJAT-32578 and FJAT-32579 were deposited in GenBank (ITS, OM920986 and OM920987; BenA, OM953825 and OM953826). All sequences showed above 99% similarity to P. ochrochloron type strain CBS357.48 (ITS, NR111509; BenA, GU981672). In multilocus phylogenetic analysis (ITS + BenA), the two isolates from this study clustered together with other strains of P. ochrochloron with 100% bootstrap support. The two isolates were thus identified as P. ochrochloron based on both morphological and molecular characteristics. Pathogenicity tests were conducted in triplicate by inoculating the aseptic wounds with 10 µl of conidial suspension (1×106 conidia/ml) of the two isolates in the each healthy tuberous root (cv. Zheshen No.1). The experiment was conducted twice. All the inoculated tuberous roots were placed in sterilized Petri dishes with moistened filter paper, and incubated at 25 ± 2 °C. Fifteen days after inoculation, all inoculated tuberous roots demonstrated the same symptoms as those observed in the field conditions. The re-isolated fungi from the artificially infected tuberous roots were confirmed as P. ochrochloron using the method described above, while the control tuberous roots treated with sterile water did not develop symptoms, fulfilling Koch's postulates. To our knowledge, this is the first report of P. ochrochloron causing green mold disease on P. heterophylla in China, which would be a potentially new threat to the medicinal plant.

An avirulent Ralstonia solanacearum strain FJAT1458 outcompetes with virulent strain and induces tomato plant resistance against bacterial wilt.

BACKGROUND: Bacterial wilt (BW) caused by Ralstonia solanacearum (RS) is considered as one of the most destructive plant diseases. An avirulent strain of RS, FJAT1458, is a potential biocontrol agent of BW. In this study, the mechanism of FJAT1458 against BW was evaluated. RESULTS: FJAT1458 was tagged with the red fluorescent protein gene, and the resulting strain was named as FJAT1458-RFP. When FJAT1458-RFP and FJAT91-GFP (a virulent strain of RS labelled with the green fluorescent protein gene), were co-inoculated in potted tomato plants, the colonization of FJAT91-GFP reached an almost undetectable level at 7 days post-inoculation (dpi) in the roots and at 9 dpi in rhizosphere soil. When they were co-inoculated in a hydroponic tomato growing system, numbers of the two strains were similar at 3 dpi in the root tissues; however, FJAT91-GFP was not detected at 9 dpi while FJAT1458-RFP maintained 1.77 × 105 CFU g-1 . The inoculation of FJAT1458-RFP alone or combination with FJAT91-GFP significantly increased tomato root activity. Moreover, expression levels of the defense-related genes PR-1a, GLUA, and CHI3 in tomato roots were significantly up-regulated by FJAT1458-RFP and co-inoculation of FJAT1458-RFP and FJAT91-GFP at 5 dpi, compared to the control (water, CK) treatment. Noteworthy, expression levels of GLUA in the treatments of FJAT1458-RFP and FJAT1458-RFP + FJAT91-GFP were 12.22- and 12.05-fold higher than that in the CK at 5 dpi, respectively. CONCLUSIONS: The results suggested that the avirulent strain FJAT1458-RFP could suppress colonization of the virulent strain in tomato roots, and induce tomato plant resistance against BW. © 2022 Society of Chemical Industry.

Sodium-glucose co-transporter-2 inhibitors reduce the risk of new-onset stroke in patients with type 2 diabetes: A population-based cohort study.

Background: Epidemiological evidence suggests the association of diabetes with an increased risk of stroke. Clinical studies have investigated the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors on new-onset stroke (NOS), but the results are inconsistent. Objectives: To determine the association between the use of SGLT2 inhibitors and NOS in patients with type 2 diabetes mellitus (DM). Methods: We conducted a retrospective longitudinal cohort study based on the Taiwan Health Insurance Review and Assessment Service database (2016-2019). The primary outcome of the assessment was the risk of incident stroke by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression was applied to estimate the adjusted HR of NOS. Subgroup analysis was also conducted. Results: Among the 232,101 eligible patients with type 2 DM aged ≥ 20 years, SGLT2-inhibitor users were compared with non-SGLT2-inhibitor users based on age, sex, and the duration of type 2 DM matching at a ratio of 1:2. The event rate per 10 000 person-months was 9.20 (95% CI 8.95 to 9.45) for SGLT2-inhibitor users and 10.5(10.3-10.6) for non-SGLT2-inhibitor users. There was a decreased risk of NOS for SGLT2-inhibitor users (adjusted HR 0.85, 95% CI 0.82-0.88) compared with non-SGLT2-inhibitor users. Results for the propensity score-matched analyses showed similar results (adjusted HR 0.87, 95% CI 0.84-0.91 for both SGLT2-inhibitor users and non-SGLT2-inhibitor users). Conclusion: The risk of developing NOS was lower in patients with SGLT2-inhibitor users than in non-SGLT2-inhibitor users. The decreased risk of NOS in patients with type 2 DM was greater among patients with concurrent use of statins, biguanides, thiazolidinediones, and glucagon-like peptide-1 receptor agonists. We, therefore, suggest that the long-term use of SGLT2 inhibitors may help reduce the incidence of NOS in patients with type 2 DM.

Development of xanthan gum/hydroxypropyl methyl cellulose composite films incorporating tea polyphenol and its application on fresh-cut green bell peppers preservation.

The aim of this work was to develop an edible packaging material with good performance that can be used for fresh-cut vegetables preservation. The xanthan (XG)-hydroxypropyl methylcellulose (HPMC)-tea polyphenols (TP) composite film (XHT) was prepared by adding TP to the composite film-forming solution of XG and HPMC. At optimum TP dosage of 6% (XHT6), the tensile strength and elongation at break were at the maximum. The antioxidant activity and antibacterial properties were also enhanced, demonstrated good inhibitory ability to Staphylococcus aureus. After 8 days, the amount of Vitamin C that was retained by XHT6 was 127.81% and 7.83% higher than unpackaged and XHT0, respectively. Additionally, the MDA content in green peppers were 39.16% and 78.87% higher than that of unpackaged and XHT0, respectively. Practical applications of XHT films in preserving fresh-cut bell peppers had also shown positive results, making it possible as potential food packaging.

Polyvinyl alcohol/xanthan gum composite film with excellent food packaging, storage and biodegradation capability as potential environmentally-friendly alternative to commercial plastic bag.

Polyvinyl alcohol (PVA)-xanthan gum (XG) composite films with good degradation properties were prepared by casting method. The effects of XG amount on thickness, moisture content, water solubility, water vapor transmission (WVP), transmittance and mechanical properties of the composite film were investigated. All composite films produced uniform and transparent films and Fourier transform infrared (FT-IR) spectroscopy, as well as X-ray diffraction (XRD) had proven the formation of hydrogen bonds and subsequently compatibility of the two polymers. In general, addition of XG in PVA was able to decrease moisture content, water solubility and WVP more than the pure PVA films, with sample PX30 demonstrated the best performance. This sample also had the best mechanical properties. It also demonstrated food packaging and capability better than that of commercial plastic bag. More importantly, our sample can be fully decomposed in soil and water within 12 h, which was not only significantly shorter than commercial plastic bag, but also other biodegradable materials. Therefore, PVA/XG-based food packaging material has demonstrated huge potential to be commercialized and replaces commercial plastic bag as an alternative packing material which is renewable, sustainable and environmentally friendly.

SNRPD1/E/F/G Serve as Potential Prognostic Biomarkers in Lung Adenocarcinoma.

Objectives: Sm proteins (SNRPB/D1/D2/D3/E/F/G), involved in pre-mRNA splicing, were previously reported in the tumorigenesis of several cancers. However, their specific role in lung adenocarcinoma (LUAD) remains obscure. Our study aims to feature abnormal expressions and mutations of genes for Sm proteins and assess their potential as therapeutic targets via integrated bioinformatics analysis. Methods: In this research, we explored the expression pattern and prognostic worth of genes for Sm proteins in LUAD across TCGA, GEO, UALCAN, Oncomine, Metascape, David 6.8, and Kaplan-Meier Plotter, and confirmed its independent prognostic value via univariate and multivariate cox regression analysis. Meanwhile, their expression patterns were validated by RT-qPCR. Gene mutations and co-expression of genes for Sm proteins were analyzed by the cBioPortal database. The PPI network for Sm proteins in LUAD was visualized by the STRING and Cytoscape. The correlations between genes for Sm proteins and immune infiltration were analyzed by using the "GSVA" R package. Results: Sm proteins genes were found upregulated expression in both LUAD tissues and LUAD cell lines. Moreover, highly expressed mRNA levels for Sm proteins were strongly associated with short survival time in LUAD. Genes for Sm proteins were positively connected with the infiltration of Th2 cells, but negatively connected with the infiltration of mast cells, Th1 cells, and NK cells. Importantly, Cox regression analysis showed that high SNRPD1/E/F/G expression were independent risk factors for the overall survival of LUAD. Conclusion: Our study showed that SNRPD1/E/F/G could independently predict the prognostic outcome of LUAD and was correlated with immune infiltration. Also, this report laid the foundation for additional exploration on the potential treatment target's role of SNRPD1/E/F/G in LUAD.

Multi-Dose Priming Regimens of PfSPZ Vaccine: Safety and Efficacy against Controlled Human Malaria Infection in Equatoguinean Adults.

Plasmodium falciparum sporozoites (PfSPZ) Vaccine is composed of radiation-attenuated, aseptic, purified cryopreserved PfSPZ. Multiple clinical trials empirically assessing two to six doses have shown multi-dose priming (-two to four doses the first week) to be optimal for protection in both 4- and 16-week regimens. In this randomized, double-blind, normal saline (NS), placebo-controlled trial, four groups (G) of 18- to 32-year-old Equatoguineans received multi-dose priming regimens with or without a delayed final dose at 4 or 16 weeks (9 × 105 PfSPZ/dose). The regimens were G1: days 1, 3, 5, 7, and 113; G2: days 1, 3, 5, and 7; G3: days 1, 3, 5, 7, and 29; and G4: days 1, 8, and 29). All doses were 9 × 105 PfSPZ. Tolerability, safety, immunogenicity, and vaccine efficacy (VE) against homologous-controlled human malaria infection (CHMI) 6-7 weeks after vaccination were assessed to down-select the best regimen. All four regimens were safe and well tolerated, with no significant differences in adverse events (AEs) between vaccinees (N = 84) and NS controls (N = 20) or between regimens. Out of 19 controls, 13 developed Pf parasitemia by quantitative polymerase chain reaction (qPCR) after CHMI. Only the vaccine regimen administered on study days 1, 8, and 29 gave significant protection (7/21 vaccinees versus 13/19 controls infected, VE 51.3%, P = 0.03, Barnard's test, two-tailed). There were no significant differences in antibodies against Pf circumporozoite protein (PfCSP), a major SPZ antigen, between protected and nonprotected vaccinees or controls pre-CHMI. The six controls not developing Pf parasitemia had significantly higher antibodies to blood stage antigens Pf exported protein 1 (PfEXP1) and Pf merozoite surface protein 1 (PfMSP1) than the controls who developed parasitemia, suggesting naturally acquired immunity against Pf-limited infections in controls. This study identified a safe, protective, 4-week, multi-dose prime vaccination regimen for assessment in future trials of PfSPZ Vaccine.

Postoperative Sedation Duration as an Independent Risk Factor for Postoperative Pneumonia in Head and Neck Cancer Patients Undergoing Free Flap Reconstruction.

OBJECTIVE: Patients who had reconstruction for head and neck cancer usually have long duration of postoperative sedation and intensive care. This is due to the complex nature of large-area soft tissue defect surgeries and upper respiratory tract infections associated with them. Postoperative pulmonary complications are common in these patients. In this study, we analyzed the risk factors and the relationship between postoperative complications and the duration of sedation to improve the patients' recovery process after free flap reconstruction for head and neck surgery. MATERIALS AND METHODS: This was a retrospective study that included 188 patients who had head and neck surgery with free flap reconstruction in 2011 (traditional recovery group) and 2018 (early recovery group). Postoperative recovery events were compared between the 2 groups. Complications such as pneumonia, wound infection, vascular thrombosis, and bleeding were also analyzed. RESULTS: The results showed that the early recovery group had a shorter duration of sedation (P < 0.001), shorter duration of intensive care unit stay (P = 0.05), more rapid ventilator weaning (P < 0.001), and fewer pneumonia events (8.8% vs 39.1%) than the traditional recovery group. Wound- and vessel-related complications were not affected by the duration of sedation. CONCLUSIONS: Our study demonstrated that shortening the duration of postoperative sedation can effectively decrease the length of intensive care unit stay and reduce postoperative incidence of pneumonia without increasing wound- and vessel-related complications.

Two genomic regions of a sodium azide induced rice mutant confer broad-spectrum and durable resistance to blast disease.

Rice blast, one of the most destructive epidemic diseases, annually causes severe losses in grain yield worldwide. To manage blast disease, breeding resistant varieties is considered a more economic and environment-friendly strategy than chemical control. For breeding new resistant varieties, natural germplasms with broad-spectrum resistance are valuable resistant donors, but the number is limited. Therefore, artificially induced mutants are an important resource for identifying new broad-spectrum resistant (R) genes/loci. To pursue this approach, we focused on a broad-spectrum blast resistant rice mutant line SA0169, which was previously selected from a sodium azide induced mutation pool of TNG67, an elite japonica variety. We found that SA0169 was completely resistant against the 187 recently collected blast isolates and displayed durable resistance for almost 20 years. Linkage mapping and QTL-seq analysis indicated that a 1.16-Mb region on chromosome 6 (Pi169-6(t)) and a 2.37-Mb region on chromosome 11 (Pi169-11(t)) conferred the blast resistance in SA0169. Sequence analysis and genomic editing study revealed 2 and 7 candidate R genes in Pi169-6(t) and Pi169-11(t), respectively. With the assistance of mapping results, six blast and bacterial blight double resistant lines, which carried Pi169-6(t) and/or Pi169-11(t), were established. The complementation of Pi169-6(t) and Pi169-11(t), like SA0169, showed complete resistance to all tested isolates, suggesting that the combined effects of these two genomic regions largely confer the broad-spectrum resistance of SA0169. The sodium azide induced mutant SA0169 showed broad-spectrum and durable blast resistance. The broad resistance spectrum of SA0169 is contributed by the combined effects of two R regions, Pi169-6(t) and Pi169-11(t). Our study increases the understanding of the genetic basis of the broad-spectrum blast resistance induced by sodium azide mutagenesis, and lays a foundation for breeding new rice varieties with durable resistance against the blast pathogen.

Development of hydroxypropyl methylcellulose film with xanthan gum and its application as an excellent food packaging bio-material in enhancing the shelf life of banana.

A novel film composed of xanthan gum (XG) and hydroxypropyl methylcellulose (HPMC) was prepared (XH). The films were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The light transmittance, mechanical properties and water vapor transmission rate (WVTR) indicated the good compatibility between XG and HPMC with hydrogen-bond interaction and XG had a significant effect on the chemical structure, crystalline texture and microstructure of the XH composite film. The best XH sample with optimum XG concentration of 2 g/L was used as food packaging via coating onto banana, whereby the weight loss rate on banana was able to decreased from 25 ± 3% (without XH coating) to 16 ± 4% (with XH coating). Consequently, the release of flavor substances was also decreased. Banana shelf life has qualitatively improved with XH composite film for food preservation and affirmed the uses in food packaging applications.