Pre- and postharvest measures used to control decay and mycotoxigenic fungi in potato (Solanum tuberosum L.) during storage.

Potato (Solanum tuberosum L.), a worldwide, staple food crop, is susceptible to postharvest rots caused by a variety of fungal pathogens, including Fusarium spp., Alternaria spp., Phytophthora infestans, Helminthosporium solani, Rhizoctonia solani, and Colletotrichum coccodes. Rots resulting from infections by these pathogens cause a significant reduction in potato quality and marketable yield. Importantly, some of these decay fungi also produce mycotoxins that represent a potential risk to human health. In the present review, an overview and discussion are provided on the epidemiology and pathogenesis of decay fungi, especially Fusarium spp., that include recent data derived from genomic and phylogenetic analyses. The biosynthesis and functional role of fungitoxic metabolites such as trichothecene mycotoxins and fusaric acid, produced in rotted potatoes are also reviewed. Advances in pre- and postharvest measures for rot management, especially eco-friendly methods including physical control, biological control, the use of natural compounds, and other agricultural management practices are also reviewed. Lastly, novel approaches to control potato dry rot such as the use of mycoviruses and CRISPR technology are highlighted.

Rapid Conversion of Co2+ to Co3+ by Introducing Oxygen Vacancies in Co3O4 Nanowire Anodes for Nitrogen Removal with Highly Efficient H2 Recovery in Urine Treatment.

Urine is a nitrogenous waste biomass but can be used as an appealing alternative substrate for H2 recovery. However, urine electrolysis suffers from sluggish kinetics and requires alkaline condition. Herein, we report a novel system to decompose urine to H2 and N2 under neutral conditions mediated by Cl• using oxygen-vacancy-rich Co3O4 nanowire (Ov-Co3O4) anodes and CuO nanowire cathodes. The Co2+/Co3+ cycle in Co3O4 activates Cl- in urine to Cl•, which rapidly and selectively converts urea into N2. Thus, electron transfer is boosted for H2 production, eliminating the kinetic limitations. The shuttle of Co2+ to Co3+ is the key step for Cl• yield, which is accelerated due to the introduction of Ov. Electrochemical analysis shows that Ov induces positive charge on the Co center; therefore, Co2+ loses electrons more efficiently to form Co3+. H2 production in this system reaches 716 µmol h-1, which is 320% that of non-radical-mediated urine electrolysis. The utilization of Ov-Co3O4 further enhances H2 generation, which is 490 and 210% those of noble Pt and RuO2, respectively. Moreover, urine is effectively degraded in 90 min with the total nitrogen removal of 95.4%, and N2 is the final product. This work provides new insights for efficient and low-cost recovery of H2 and urine remediation.

Interferon-γ enhances the immunosuppressive ability of canine bone marrow-derived mesenchymal stem cells by activating the TLR3-dependent IDO/kynurenine pathway.

BACKGROUND: The immunomodulatory function of mesenchymal stem cells (MSCs) has been considered to be vital for MSC-based therapies. Many works have been devoted to excavate effective strategies for enhancing the immunomodulation effect of MSCs. Nonetheless, canine MSC-mediated immunomodulation is still poorly understood. METHODS AND RESULTS: The inflammatory microenvironment was simulated through the employment of interferon-γ (IFN-γ) in a culture system. Compared with unstimulated cBMSCs, IFN-γ stimulation increased the mRNA levels of Toll-like receptor 3 (TLR3) and indoleamine 2, 3-dioxygenase 1 (IDO-1), and simultaneously enhanced the secretion of immunosuppressive molecules, including interleukin (IL)-10, hepatocyte growth factor (HGF), and kynurenine in cBMSCs. IFN-γ stimulation significantly enhanced the ability of cBMSCs and their supernatant to suppress the proliferation of murine spleen lymphocytes. Lymphocyte subtyping evaluation revealed that cBMSCs and their supernatant diminished the percentage of CD3+CD4+ and CD3+CD8+ lymphocytes compared with the control group, with a decreasing CD4+/CD8+ ratio. Notably, exposure to IFN-γ decreased the CD4+/CD8+ ratio more effectively than unstimulated cells or supernatant. Additionally, IFN-γ-stimulation increased the mRNA levels of the Th1 cytokines TNF-α, and remarkably decreased the mRNA level of the Th2 cytokine IL-4 and IL-10. CONCLUSION: Our findings substantiate that IFN-γ stimulation can enhance the immunomodulatory properties of cBMSCs by promoting TLR3-dependent activation of the IDO/kynurenine pathway, increasing the secretion of immunoregulatory molecules and strengthening interactions with T lymphocytes, which may provide a meaningful strategy for the clinical application of cBMSCs in immune-related diseases.

Effect of three aging processes on physicochemical and As(V) adsorption properties of Ce/Mn-modified biochar.

Modified biochar used for soil remediation is affected by exposure to the environment and aging process results in changes in its physicochemical properties and As(V) adsorption and immobilization in soil. Herein, the Ce/Mn-modified wheat straw-biochar (MBC) was manufactured and then aged through three artificial aging processes by exposure to soil with additional natural, freeze-thaw, and dry-wet cycles involved. It revealed that the specific surface areas of freeze-thaw-aged MBC reached 214.98 m2/g and was increased more than those of other two aging treatments. In addition, the pH values and C contents of MBC all decreased after aging while the H and O contents increased. Correspondingly, the contents of O-containing functional groups like C-O, -OH, and CO all increased by >16% with aging. The freeze-thaw cycling and alternating dry-wet aging treatments improved adsorption capacities of As(V) onto MBC and were increased by 16.2 and 10.6% at pH 5, respectively and these samples exhibited the best recyclability and adsorption selectivity for As(V). However, natural aging exerted a lower effect for As(V) adsorption by MBC due to its few changes on physicochemical properties. Causally, the freeze-thaw and dry-wet aging activated the Ce/Mn-oxides to generate Mn2+/3+ species and a new mono-Ce that exerted a strong bonding complexation with As(V) to form Ce/Mn-O-As ligands and increased CeAsO4 precipitation. Our results offer a new insight into the alterations expected for modified biochars with aging treatment in terms of As(V) adsorption for its long-term utilization in As contaminated soil.

An antisense Alu transposon insertion/deletion polymorphism of ALDH1A1 may functionally associate with Parkinson's disease.

BACKGROUND: Aldehyde dehydrogenase 1 (encoded by ALDH1A1) has been shown to protect against Parkinson's disease (PD) by reducing toxic metabolites of dopamine. We herein revealed an antisense Alu element insertion/deletion polymorphism in intron 4 of ALDH1A1, and hypothesized that it might play a role in PD.  METHODS: A Han Chinese cohort comprising 488 PD patients and 515 controls was recruited to validate the Alu insertion/deletion polymorphism following a previous study of tag-single nucleotide polymorphisms, where rs7043217 was shown to be significantly associated with PD. Functional analyses of the Alu element insertion were performed. RESULTS: The Alu element of ALDH1A1 was identified to be a variant of Yb8 subfamily and termed as Yb8c4. The antisense Yb8c4 insertion/deletion polymorphism (named asYb8c4ins and asYb8c4del, respectively) appeared to be in a complete linkage disequilibrium with rs7043217 and was validated to be significantly associated with PD susceptibility with asYb8c4ins serving as a risk allele (P = 0.030, OR = 1.224, 95% CI = 1.020-1.470). Multiple functional analyses including ALDH1A1 mRNA expression in blood cells of carriers, and reporters of EGFP and luciferase showed that the asYb8c4ins had a suppressive activity on gene transcription. Mechanistic explorations suggested that the asYb8c4ins induced no changes in CpG methylation and mRNA splicing of ALDH1A1 and appeared no binding of transcription factors. CONCLUSIONS: Our results consolidate an involvement of ALDH1 in PD pathogenesis. The asYb8c4 polymorphism may be a functional output of its linkage disequilibrium-linked single nucleotide polymorphisms.

Autophagy: a promising therapeutic target for improving mesenchymal stem cell biological functions.

Mesenchymal stem cells (MSCs) are considered to be a promising therapeutic material due to their capacities for self-renewal, multilineage differentiation, and immunomodulation and have attracted great attention in regenerative medicine. However, MSCs may lose their biological functions because of donor age or disease and environmental pressure before and after transplantation, which hinders the application of MSC-based therapy. As a major intracellular lysosome-dependent degradative process, autophagy plays a pivotal role in maintaining cellular homeostasis and withstanding environmental pressure and may become a potential therapeutic target for improving MSC functions. Recent studies have demonstrated that the regulation of autophagy is a promising approach for improving the biological properties of MSCs. More in-depth investigations about the role of autophagy in MSC biology are required to contribute to the clinical application of MSCs. In this review, we focus on the role of autophagy regulation by various physical and chemical factors on the biological functions of MSCs in vitro and in vivo, and provide some strategies for enhancing the therapeutic efficacy of MSCs.

Effects of mouth breathing on facial skeletal development in children: a systematic review and meta-analysis.

BACKGROUND: Mouth breathing is closely related to the facial skeletal development and malocclusion. The purpose of this systematic review and meta-analysis was to assess the effect of mouth breathing on facial skeletal development and malocclusion in children. METHODS: An electronic search in PubMed, the Cochrane Library, Medline, Web of Science, EMBASE and Sigle through February 23rd, 2020, was conducted. Inclusion criteria were children under 18 years of age with maxillofacial deformities due to mouth breathing. The risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. The included indicators were SNA, SNB, ANB, SN-OP, SN-PP, PP-MP, SNGoGn, MP-H, 1-NA, 1. NA, 1. NB, 1-NB, Overjet, Overbite, SPAS, PAS, and C3-H. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean differences and 95% confidence intervals were analyzed for continuous data. Review Manager 5.3, was used to synthesize various parameters associated with the impact of mouth breathing on facial skeletal development and malocclusion. RESULTS: Following full-text evaluations for eligibility, 10 studies were included in the final quantitative synthesis. In Sagittal direction, SNA (MD: - 1.63, P < 0.0001), SNB (MD: - 1.96, P < 0.0001) in mouth-breathing children was lower than that in nasal-breathing children. ANB (MD: 0.90, P < 0.0001), 1. NA (MD: 1.96, P = 0.009), 1-NA (MD: 0.66, P = 0.004), and 1-NB (MD: 1.03, P < 0.0001) showed higher values in children with mouth breathing. In vertical direction, SN-PP (MD: 0.68, P = 0.0050), SN-OP (MD: 3.05, P < 0.0001), PP-MP (MD: 4.92, P < 0.0001) and SNGoGn (MD: 4.10, P < 0.0001) were higher in mouth-breathing individuals. In airway, SPAS (MD: - 3.48, P = 0.0009), PAS (MD: - 2.11, P < 0.0001), and C3-H (MD: - 1.34, P < 0.0001) were lower in mouth breathing group. CONCLUSIONS: The results showed that the mandible and maxilla rotated backward and downward, and the occlusal plane was steep. In addition, mouth breathing presented a tendency of labial inclination of the upper anterior teeth. Airway stenosis was common in mouth-breathing children. Trial registration crd-register@york.ac.uk, registration number CRD42019129198.

[PVT1 Promoted the Proliferation and Migration Ability of BMSCs in Glioma C6 Microenvironment].

OBJECTIVE: To investigate the changes in the proliferation and migration ability of bone marrow mesenchymal stem cells (BMSCs) after indirect co-culturing with glioma C6 cells, and to examine the role of plasmacytoma variant translocation 1 gene ( PVT1), a long non-coding RNA (lncRNA), in these changes. METHODS: After separation, cultivation and identification of BMSCs, BMSCs of good growth condition were picked out and indirectly co-cultured with glioma C6 cells in Transwell chambers. These cells are henceforth referred to as the co-culture group. Normal BMSCs cultured separately were the control group. CCK-8 and soft agar colony formation assay were used to examine the proliferation ability of the two groups of cells. Flow cytometry was used to examine the cell cycle. Wound healing assay and Transwell assay were used to explore the migration ability of the cells. Quantitative real-time PCR (qRT-PCR) was used to examine the genetic expression level of PVT1 in the two groups. The above-mentioned tests were repeated after the co-cultured BMSCs were transfected with si- PVT1 (si- PVT1 group) and si-NC (si-NC group). In addition, qRT-PCR was done to evaluate the expression of CyclinD1, a cell cycle protein gene, and matrix metalloproteinases 2 and 9 ( MMP2 and MMP9), the migration-related genes in the si- PVT1 and si-NC transfected co-cultured BMSCs. RESULTS: The BMSCs used in the present study possess the capability of osteogeneic and adipogenic differentiation. Compared with the control group, the co-cultured BMSCs had smaller size, disorderly arrangement and the lack of intercellular contact inhibition. The proliferation and migration ability was significantly enhanced, the proportions of S and G 2 phase cells greatly increased and the expression level of PVT1 was significantly up-regulated ( P<0.05) in the co-cultured group in comparison with those of the control group. When compared with the si-NC group, the si- PVT1 group showed inhibited proliferation and migration ability of the co-cultured BMSCs; the percentage of G 1 phase cells increased, while that of S phase decreased; the expression of PVT1, CyclinD1, MMP2 and MMP9 mRNA also decreased ( P<0.05) in the si- PVT1 group. CONCLUSION: The enhanced proliferation and migration ability of BMSCs in the glioma C6 microenvironment may be associated with the up-regulated expression of PVT1 .

Association between a functional interleukin 6 receptor genetic variant and the risk and functional outcome of large artery atherosclerotic stroke.

Purpose: To investigate whether the Asp358Ala of interleukin 6 receptor related to the risk and outcome of large artery atherosclerotic (LAA) stroke in Han Chinese.Materials and methods: A prospective cohort study was conducted on 768 patients with LAA stroke and 686 non-stroke controls. The genotypes of Asp358Ala polymorphism were determined using SNPscan technology. Associations between genotypes and the risk of LAA stroke were analyzed with logistic regression model.Results: CC genotype (P < 0.001) and AC genotype (P = 0.023) decreased the risk of LAA stroke compared with AA genotype. Multivariate logistic regression analysis revealed that CC genotype was significantly associated with the risk of LAA stroke (P = 0.002). In the subgroup analyses, polymorphisms of Asp358Ala were significantly associated with the risk of LAA stroke in additive model, dominant model and recessive model (P = 0.009, P = 0.017, P = 0.012, respectively) for male, but not for female. Further regression analysis showed that compared with participants with AA genotype and obesity, participants with CC genotype and non-obesity were less likely to suffer LAA stroke (P = 0.003). For male participants, these associations were still existed (additive model, P = 0.022). After 3-month follow-up, patients with C allele had good functional prognosis compared with patients with A allele (P = 0.009).Conclusion: The study demonstrated that the Asp358Ala polymorphism might be associated with susceptibility to the development and outcome of LAA stroke in Han Chines.

Association of Matrix Metalloproteinase-1 and Matrix Metalloproteinase-3 Gene Variants with Ischemic Stroke and Its Subtype.

BACKGROUND: Genetic variations in the genes of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of ischemic stroke (IS). Here we investigate the association between MMP-1 -1607 1G/2G and MMP-3 -1171 5A/6A genetic polymorphisms and etiological subtypes of IS in the Han Chinese population. METHODS: A total of 640 eligible patients with IS and 637 age- and gender-matched apparently healthy volunteers were enrolled. Subtypes of IS were classified by Trial of Org 10172 in Acute Stroke Treatment criteria. MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms were evaluated using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequencies of the 5A/6A + 5A/5A genotypes and 5A allele were significantly higher in patients with IS than in controls (P <.001, P <.001, respectively). No association was found between MMP-1 1G/2G polymorphism and overall IS. In subgroup analyses, MMP-1 1G/2G and 2G/2G genotypes increased the risk of small-artery occlusion (SAO) subtype (multivariate-adjusted, P <.001, P = .002, respectively), and MMP-3 5A/6A + 5A/5A genotypes were related with large-artery atherosclerosis (LAA) subtype (multivariate-adjusted, P <.001). Haplotype analyses indicated that 2G-6A and 1G-5A increased the risk of SAO (multivariate-adjusted, P = .029) and LAA (multivariate-adjusted, P <.001), respectively. CONCLUSIONS: MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms may contribute to different subtypes of IS susceptibility.

No Association Between High-Sensitivity C-Reactive Protein and Carotid Intima-Media Progression: The APAC Study.

BACKGROUND AND PURPOSE: High-sensitivity C-reactive protein (hs-CRP) is a risk indicator for atherosclerosis. However, the association between hs-CRP and early carotid atherosclerosis progression is not well established. We undertook a prospective, community-based, observational study to address this question. METHODS: Common carotid artery intima-media thickness (IMT) and hs-CRP values were measured at baseline and after 2 years of follow-up in subjects ≥40 years of age who were participating in the Asymptomatic Polyvascular Abnormalities Community study. Association between hs-CRP values and IMT progression was determined before and after controlling for vascular risk factors. RESULTS: IMT was measured in a total of 1918 subjects at baseline and 52.97% of those (1016 of 1918) had IMT progression after 2 years. No significant association between progression of IMT over a 2-year period and average hs-CRP levels was found (multivariate-adjusted, P for trend = .280). Both hs-CRP values measured at baseline (P = .836) and after 2 years of follow-up (P = .440) were not associated with IMT progression levels. Average hs-CRP values were not related to IMT progression levels in a dose-response manner (P = .784). In a subgroup analysis stratified by age and sex, hs-CRP values were also not significantly associated with IMT progression levels (P > .05). CONCLUSION: Our results suggest that hs-CRP is not a predictor for the progression of early atherosclerotic changes of the carotid arteries. The hs-CRP levels in early atherosclerosis might be considered as risk markers rather than having a causal role.

Impact of 5A/6A polymorphism of matrix metalloproteinase-3 on recurrent atherosclerotic ischemic stroke in Chinese.

Little is known about the impact of the 5A/6A polymorphism of matrix metalloproteinase-3 (MMP-3) on recurrence of atherosclerotic ischemic stroke in Chinese. The aim of this study was to investigate the association of MMP-3 serum level and 5A/6A genetic polymorphism with the recurrence of atherosclerotic ischemic stroke in the Chinese Han population. We analyzed 106 large artery atherosclerosis (LAA) recurrent ischemic stroke patients and 545 LAA first onset ischemic stroke patients from January 2009 to June 2014. Serum MMP-3 concentrations were measured with an enzyme-linked immunosorbent assay. The genotypes of MMP-3 promoter polymorphism (-1171 5A/6A) were determined using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of MMP-3 5A/6A+5A/5A (32.08% vs. 21.47%, p = 0.02) genotype and 5A (16.98% vs. 11.01%, p = 0.01) allele in the recurrent group was significantly higher than those in the first onset group. After adjustment for vascular risk factors, multivariate logistic regression analysis suggested that the MMP-3 5A/6A+5A/5A genotype was an independent risk factor for LAA recurrent ischemic stroke (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.09-2.79, p = 0.021). No significant difference was observed for the MMP-3 serum concentrations between the recurrent group and the first onset group (22.23 ± 8.31 vs. 21.49 ± 7.89 ng/ul, t = 0.88, p = 0.38). The MMP-3 (-1171 5A/6A) polymorphism may contribute to LAA recurrent ischemic stroke susceptibility. Analysis of 5A/6A polymorphism in MMP-3 may identify patients at higher risk for LAA ischemic stroke recurrence, who may be selected for intensive preventive therapy.

Three-phase hollow-fiber microextraction combined with ion-pair high-performance liquid chromatography for the simultaneous determination of five components of compound α-ketoacid tablets in human urine.

The determination of α-ketoacid concentration is demanded to evaluate the absorption and metabolic behavior of compound α-ketoacid tablets taken by chronic kidney disease patients. To eliminate the interference of endogenous substance of urine and enrich the analytes, a three-phase hollow-fiber liquid-phase microextraction combined with ion-pair high-performance liquid chromatography method was established for the determination of d,l-α-hydroxymethionine calcium, d,l-α-ketoisoleucine calcium, α-ketovaline calcium, α-ketoleucine calcium, and α-ketophenylalanine calcium of compound α-ketoacid tablets in human urine samples. The extraction parameters, such as organic solvent, pH of donor phase and acceptor phase, stirring rate, and extraction time were optimized. Under the optimal conditions, the obtained enrichment factors were up to 11-, 110-, 198-, 202-, and 50-fold, respectively. The calibration curves for these analytes were linear over the range of 0.1-10 mg/L for α-ketovaline calcium, d,l-α-ketoisoleucine calcium, and α-ketoleucine calcium, 0.5-10 mg/L for d,l-α-hydroxymethionine calcium, and α-ketophenylalanine calcium with r > 0.99. The relative standard deviations (n = 5) were less than 6.27% and the LODs were 100.7, 10.0, 5.8, 7.8, and 8.6 µg/L (based on S/N = 3), respectively. Good recoveries from spiked urine samples (92-118%) were obtained. The proposed method demonstrated excellent sample clean-up and analytes enrichment to determine the five components in human urine.

"Sandwich" Structure in Reconstruction of Traumatic Comminuted Anterior Skull Base Fractures: Surgical Technique and Outcomes.

BACKGROUND: Comminuted fractures of the anterior skull base can easily cause dural damage, leading to cerebrospinal fluid leakage and retrograde infection. Skull base reconstruction is essential. This study aimed to present a novel and simple technique for repairing skull base defects using a self-made fascia-bone fragments-fascia "sandwich" structure made by fascia, fracture fragments, and sutures. METHOD: From 2018 to 2023, we performed self-made sandwich structures for skull reconstruction in 10 patients with anterior skull base comminuted fractures. After debridement, the intracranial bone fragments of the surgical patient were safely removed. In vitro, the bone fragments were spread between two layers of temporal or broad fascia to form a sandwich structure similar to the size of the bone defect, and the periphery was firmly sutured with sutures. The self-made structure was then filled to the defect and fixed with fibrin glue. The periosteum at the top of the forehead was also turned over to the repair area for covering and fixation. Meanwhile, a facial skin cosmetic suture was performed. Finally, we evaluate the feasibility and efficacy of this technique. RESULTS: All 10 patients underwent reconstructive surgery using the self-made fascia-fracture fragments-fascia sandwich structure. Five patients with open wounds on the face also underwent cosmetic revisions. No cerebrospinal fluid leakage occurred in all the patients at discharge as well as 3 months later. CONCLUSIONS: For patients with comminuted fracture of the anterior skull base, the fascia-bone fragments-fascia structure could repair the skull base and prevent the occurrence of cerebrospinal fluid leakage.

Variants in 3p24.3 predicts the risk of early neurological deterioration in large artery atherosclerotic stroke.

The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP-SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49-0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients.

Clinical characteristics and prognosis of Klebsiella pneumoniae meningitis in adults.

Background: Klebsiella pneumoniae is a causative agent of bacterial meningitis in adults. However, there is little information regarding this infection. Therefore, this study comprehensively analyzed the clinical characteristics and prognosis of Klebsiella pneumoniae meningitis (KPM) patients. Methods: The clinical data of adult hospitalized patients with KPM were retrospectively collected from January 2015 to December 2022. The clinical characteristics and antibiotic resistance of KPM were evaluated. Meanwhile, a set of logistic regression models was constructed to identify prognostic factors for death. These prognostic factors were subsequently combined to develop a nomogram for predicting the risk of in-hospital mortality in individual patients. Finally, the receiver operating characteristic curve and calibrate plot were utilized to verify the performance of the nomogram. Results: This study included 80 adult patients with KPM, 58 (72.5%) of whom were males. The mortality rate was 45%. Among them, 74 (92.5%) were diagnosed with healthcare-associated meningitis. Thirty-seven carbapenem-resistant Klebsiella pneumoniae (CRKP) strains were susceptible to tigecycline, polymyxin, and ceftazidime/avibactam. CRKP (OR = 9.825, 95%CI = 2.757-35.011, P < 0.001), length of stay (OR = 0.953, 95%CI = 0.921-0.986, P = 0.005), and C-reactive protein-to-prealbumin ratio (CRP/PA, OR = 3.053, 95%CI = 1.329-7.016, P = 0.009) were identified as predictive factors for mortality using multivariate logistic regression. Finally, a nomogram for death prediction was established. The area under the curve of this nomogram was 0.900 (95% CI = 0.828-0.971). Conclusions: KPM is a fatal disease associated with high incidence of healthcare-associated infections and carbapenem resistance. Moreover, CRKP, length of stay, and CRP/PA were found to be independent predictors of mortality.

Genome-wide identification, gene expression and haplotype analysis of the rhomboid-like gene family in wheat (Triticum aestivum L.).

The rhomboid-like (RBL) gene encodes serine protease, which plays an important role in the response to cell development and diverse stresses. However, genome-wide identification, expression profiles, and haplotype analysis of the RBL family genes have not been performed in wheat (Triticum aestivum L.). This study investigated the phylogeny and diversity of the RBL family genes in the wheat genome through various approaches, including gene structure analysis, evolutionary relationship analysis, promoter cis-acting element analysis, expression pattern analysis, and haplotype analysis. The 41 TaRBL genes were identified and divided into five subfamilies in the wheat genome. RBL family genes were expanded through segmented duplication and purification selection. The cis-element analysis revealed their involvement in various stress responses and plant development. The results of RNA-seq and quantitative real-time-PCR showed that TaRBL genes displayed higher expression levels in developing spike/grain and were differentially regulated under polyethylene glycol, NaCl, and abscisic acid treatments, indicating their roles in grain development and abiotic stress response. A kompetitive allele-specific PCR molecular marker was developed to confirm the single nucleotide polymorphism of TaRBL14a gene in 263 wheat accessions. We found that the elite haplotype TaRBL14a-Hap2 showed a significantly higher 1000-grain weight than TaRBL14a-Hap11 in at least three environments, and the TaRBL14a-Hap2 was positively selected in wheat breeding. The findings will provide a good insight into the evolutionary and functional characteristics of the TaRBL genes family in wheat and lay the foundation for future exploration of the regulatory mechanisms of TaRBL genes in plant growth and development, as well as their response to abiotic stresses.

Prognostic impact of age in advanced non-small cell lung cancer patients undergoing first-line checkpoint inhibitor immunotherapy and chemotherapy treatment.

BACKGROUND: Research on the association between age and clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy combined with chemotherapy as first-line setting is limited. The aim of study is to determine the influence of age on the progress-free survival (PFS) and overall survival (OS) in those patients after adjusting for potential confounders. METHODS: A total of 207 advanced NSCLC patients treated with immunotherapy combined with chemotherapy in the first-line treatment in Guangxi Medical University Cancer Hospital from March 10, 2019, to December 31, 2022, was retrospectively analyzed. χ2 (categorical variables) was used to analyze the differences among the different age groups. Cox regression and Kaplan-Meier analyses were used to assess the association between age and clinical outcomes. P values < 0.05 (two-sided) were considered statistically significant. RESULTS: The mean age of the cohort was 58.8 ± 10.3 years. The percentages of patients < 65, 65-69, 70-74, and ≥ 75 years were 66.7 %, 19.3 %, 9.2 % and 4.8 %, respectively. Compared to the aged < 65 years group, the HR for the risk of disease progression for each group are 0.67 (95 %CI = 0.40-1.12, P = 0.125), 0.66 (95 %CI = 0.31, 1.43, P = 0.298), and 2.27 (95 %CI = 0.80, 6.45, P = 0.124), respectively, with no significant differences in the results. And the HR for risk of death for the 65-69 years and 70-74 years groups was 1.16 (95 %CI = 0.64-2.08, P = 0.628) and 0.93 (95 %CI = 0.39-2.23, P = 0.879), respectively. The difference has no statistical significance. Whereas in patients aged ≥ 75, there is an increased risk of death after adjusted confounders with HR = 4.83 (95 %CI = 2.06-11.35). The difference was statistically significant (P < 0.001). Trend test indicates that with advancing age, the patient's risk of death increases (HR = 1.33, 95 % CI = 1.02-1.75, P = 0.034). CONCLUSION: Age may not be the primary factor influencing the efficacy of immunotherapy combined with chemotherapy, but particular attention should be given to the elderly population.

An optimized high-throughput SARS-CoV-2 dual reporter trans-complementation system for antiviral screening in vitro and in vivo.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still epidemic around the world. The manipulation of SARS-CoV-2 is restricted to biosafety level 3 laboratories (BSL-3). In this study, we developed a SARS-CoV-2 ΔN-GFP-HiBiT replicon delivery particles (RDPs) encoding a dual reporter gene, GFP-HiBiT, capable of producing both GFP signal and luciferase activities. Through optimal selection of the reporter gene, GFP-HiBiT demonstrated superior stability and convenience for antiviral evaluation. Additionally, we established a RDP infection mouse model by delivering the N gene into K18-hACE2 KI mouse through lentivirus. This mouse model supports RDP replication and can be utilized for in vivo antiviral evaluations. In summary, the RDP system serves as a valuable tool for efficient antiviral screening and studying the gene function of SARS-CoV-2. Importantly, this system can be manipulated in BSL-2 laboratories, decreasing the threshold of experimental requirements.

Kiwifruit resistance to gray mold is enhanced by yeast-induced modulation of the endophytic microbiome.

The influence of endophytic microbial community on plant growth and disease resistance is of considerable importance. Prior research indicates that pre-treatment of kiwifruit with the biocontrol yeast Debaryomyces hansenii suppresses gray mold disease induced by Botrytis cinerea. However, the specific underlying mechanisms remain unclear. In this study, Metagenomic sequencing was utilized to analyze the composition of the endophytic microbiome of kiwifruit under three distinct conditions: the healthy state, kiwifruit inoculated with B. cinerea, and kiwifruit treated with D. hansenii prior to inoculation with B. cinerea. Results revealed a dominance of Proteobacteria in all treatment groups, accompanied by a notable increase in the relative abundance of Actinobacteria and Firmicutes. Ascomycota emerged as the major dominant group within the fungal community. Treatment with D. hansenii induced significant alterations in microbial community diversity, specifically enhancing the relative abundance of yeast and exerting an inhibitory effect on B. cinerea. The introduction of D. hansenii also enriched genes associated with energy metabolism and signal transduction, positively influencing the overall structure and function of the microbial community. Our findings highlight the potential of D. hansenii to modulate microbial dynamics, inhibit pathogenic organisms, and positively influence functional attributes of the microbial community.