Rapid Detection of Total Petroleum Hydrocarbons in Soil Using Advanced Fluorescence Imaging Techniques.

Chemical methods for measuring soil organic content are often slow and yield inaccurate results due to significant errors. Simple summation of components may not accurately determine total organic content. In contrast, fluorescence imaging techniques offer rapid, in situ monitoring without complex pretreatment and demonstrate rapid and accurate assessment of soil organic content. Utilizing a soil organic pollutant fluorescence imaging in situ monitoring system that we independently developed, we conducted laboratory experiments to explore methods for acquiring fluorescence signals of petroleum hydrocarbons in soil and extracting image features. We used this monitoring system to obtain fluorescence images of crude oil in standard soil (soil properties are shown in Table S1) samples at concentrations ranging from 0 to 100 g/kg, and the coefficient of determination of the total amount inversion model reached 0.999. Simultaneously, we applied the system to a deserted petroleum storage area, and the relative standard deviation values of 16 of the 18 groups of tests were less than 1%, indicating that the monitoring system is highly stable when applied in the field. This study provides both theoretical foundation and technical support for the rapid and nondestructive detection of total petroleum hydrocarbons in soil at field sites.

Transcription factor OsbZIP10 modulates rice grain quality by regulating OsGIF1.

Understanding and optimizing the process of grain filling helps the quest to maximize rice (Oryza sativa L.) seed yield and quality, yet the intricate mechanisms at play remain fragmented. Transcription factors (TFs) are major players in the gene networks underlying the grain filling process. Here, we employed grain incomplete filling (OsGIF1)/cell wall invertase 2, a key gene involved in grain filling, to explore its upstream TFs and identified a bZIP family TF, OsbZIP10, to be a transcriptional activator of OsGIF1. Rice grains of the knockouts of OsbZIP10 showed increased white-core rates but lower amylose content (AC), leading to better eating and cooking qualities in all genetic backgrounds investigated, though the impact of mutations in OsbZIP10 on grain weight depended on genetic background. Multi-omics analyses suggested that, in addition to OsGIF1, multiple genes involved in different biological processes contributing to grain filling were targeted by OsbZIP10, including OsAGPS1, a gene encoding the ADP-Glc pyrophosphorylase (AGPase) small subunit, and genes contributing to homeostasis of reactive oxygen species. Distinct genetic make-up was observed in OsbZIP10 between japonica and indica rice varieties, with the majority varieties of each subspecies belonging to two different haplotypes that were closely associated with AC. Overexpressing the haplotype linked to high-AC in the low-AC genetic background increased AC. Overall, this study sheds crucial light on the significance of the OsbZIP10-OsGIF1 module in the determination of rice grain quality, offering a potential avenue for genetic engineering of rice to produce seeds with tailored attributes.

Association between red cell distribution width and all-cause mortality in patients with breast cancer: A retrospective analysis using MIMIC-IV 2.0.

PURPOSE: Investigating the association between red cell distribution width (RDW) and all-cause mortality in patients with breast cancer, to evaluate the potential clinical prognostic value of RDW. METHODS: Based on the RDW index, patients with breast cancer in the Medical Information Mart for Intensive Care (MIMIC-IV) database were categorized into quartiles. The primary outcomes included in-hospital mortality from all causes during the first six months, the first year, and the first three years. Cox hazards regression and restricted cubic spline (RCS) models were developed to investigate the effects of RDW on primary outcomes. RESULTS: The study included 939 patients (female). The 6-month, 1-year, and 3-year mortality rates were 14.0%, 21.4%, and 28.4%, respectively. Multivariate Cox proportional hazards analyses demonstrated that RDW exhibited an autonomous association with an increased risk of all-cause mortality. After adjusting for confounders, higher RDW quartiles were significantly associated with 6-month mortality (adjusted hazard ratio (HR), 3.197; 95% confidence interval (CI), 1.745-5.762; P < 0.001), 1-year mortality (adjusted HR, 2.978; 95% CI, 1.867-4.748; P < 0.001), and 3-year mortality (adjusted HR, 2.526; 95% CI, 1.701-3.750; P < 0.001). The RCS curves demonstrated that high RDW (> 14.6) was associated with a greater risk of all-cause mortality. Subgroup analyses revealed no statistically significant differences in the interactions between the subgroups. CONCLUSION: The study revealed a highly pronounced relationship between RDW and overall mortality, indicating its potential as an autonomous prognostic factor for increased mortality among patients with breast cancer.

Determination of phenolic compounds in water using a multivariate statistical analysis method combined with three-dimensional fluorescence spectroscopy.

Phenolic compounds are toxic chemical pollutants present in water. Three-dimensional fluorescence spectroscopy analysis is an effective and rapid method for real-time phenol monitoring in aquatic environments. However, similar chemical structures of phenols result in highly overlapping three-dimensional fluorescence spectra. Therefore, it is extremely difficult to analyze and quantify the concentration of components in a mixture system that includes two or more phenolic compounds. In this article, we study the mixed phenol system containing phenol, o-cresol, p-cresol, m-cresol, catechol, and resorcinol combined with excitation-emission matrix (EEM) fluorescence data. A multivariate statistical method called best linear unbiased prediction (BLUP) is proposed to analyze the spectra with the aim to achieve quantitative results and a trilinear decomposition algorithm called parallel factor analysis (PARAFAC) was used for comparison. Two experiments with different calibration samples were set to validate the effectiveness of BLUP through recovery, ARecovery (Average Recovery), AREP (Average Relative Error of Prediction), and RMSE (Root Mean Square Error). Overall, the average recovery of each component in experiment 1 and experiment 2 ranged from 95.91% to 111.62% and 82.91% to 129.02%, respectively. Based on the results of the experiments, the concentration of phenolic compounds in water can be quantitatively determined by combining three-dimensional fluorescence spectroscopy with the BLUP method.

GLS and GOT2 as prognostic biomarkers associated with dendritic cell and immunotherapy response in breast cancer.

Breast cancer is the females' most common cancer. Targeting the immune microenvironment is a new and promising treatment method for breast cancer. Nevertheless, only a small section of patients can profit by immunotherapy, and improving the ability to accurately predict the potential for immunotherapy response is still awaiting further exploration. In this study, we found that the key factors of glutamine metabolism, glutaminase 1 (GLS) and mitochondrial aspartate transaminase (GOT2), showed opposite expression patterns in breast cancer samples. Based on the expression level of GLS and GOT2, we divided the breast cancer samples into two clusters: Cluster 2 showed GLS expressed higher and GOT2 expressed lower, whereas Cluster 1 showed GOT2 expressed higher and GLS expressed lower. GSEA showed that the clusters were related to pathways of immunity. Further analysis showed that Cluster 2 was positively associated with immunity infiltration. Through WGCNA, we identified a module strongly correlated with glutamine metabolism and immunity and identified 11 dendritic cell-associated genes involved in dendritic cell development, maturation, activation and other functions. In addition, Cluster 2 also showed higher immune checkpoint gene expression, which suggest the Cluster 2 had even better response to immunotherapy. The validation dataset could also be clustered into two groups. Cluster 2 (GLS expressed higher and GOT2 expressed lower) of the validation dataset was also positively associated with dendritic cells and a better immunotherapy response. Thus, these data indicate that GLS and GOT2 are prognostic biomarkers which closely related to dendritic cells and better reacted to immunotherapy in breast cancer.

OsNAC5 orchestrates OsABI5 to fine-tune cold tolerance in rice.

Due to its tropical origins, rice (Oryza sativa) is susceptible to cold stress, which poses severe threats to production. OsNAC5, a NAC-type transcription factor, participates in the cold stress response of rice, but the detailed mechanisms remain poorly understood. Here, we demonstrate that OsNAC5 positively regulates cold tolerance at germination and in seedlings by directly activating the expression of ABSCISIC ACID INSENSITIVE 5 (OsABI5). Haplotype analysis indicated that single nucleotide polymorphisms in a NAC-binding site in the OsABI5 promoter are strongly associated with cold tolerance. OsNAC5 also enhanced OsABI5 stability, thus regulating the expression of cold-responsive (COR) genes, enabling fine-tuned control of OsABI5 action for rapid, precise plant responses to cold stress. DNA affinity purification sequencing coupled with transcriptome deep sequencing identified several OsABI5 target genes involved in COR expression, including DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR 1A (OsDREB1A), OsMYB20, and PEROXIDASE 70 (OsPRX70). In vivo and in vitro analyses suggested that OsABI5 positively regulates COR gene transcription, with marked COR upregulation in OsNAC5-overexpressing lines and downregulation in osnac5 and/or osabi5 knockout mutants. This study extends our understanding of cold tolerance regulation via OsNAC5 through the OsABI5-CORs transcription module, which may be used to ameliorate cold tolerance in rice via advanced breeding.

SETDB2 interacts with BUBR1 to induce accurate chromosome segregation independently of its histone methyltransferase activity.

SETDB2 is a H3K9 histone methyltransferase required for accurate chromosome segregation. Its H3K9 histone methyltransferase activity was reported to be associated with chromosomes during metaphase. Here, we confirm that SETDB2 is required for mitosis and accurate chromosome segregation. However, these functions are independent of its histone methyltransferase activity. Further analysis showed that SETDB2 can interact with BUBR1, and is required for CDC20 binding to BUBR1 and APC/C complex and CYCLIN B1 degradation. The ability of SETDB2 to regulate the binding of CDC20 to BUBR1 or APC/C complex, and stabilization of CYCLIN B1 are also independent of its histone methyltransferase activity. These results suggest that SETDB2 interacts with BUBR1 to promote binding of CDC20 to BUBR1 and APC3, then degrades CYCLIN B1 to ensure accurate chromosome segregation and mitosis, independently of its histone methyltransferase activity.

Identification and functional characterization of de novo variant in the SYNGAP1 gene causing intellectual disability.

Background: Intellectual disability (ID) is defined by cognitive and social adaptation defects. Variants in the SYNGAP1 gene, which encodes the brain-specific cytoplasmic protein SYNGAP1, are commonly associated with ID. The aim of this study was to identify novel SYNGAP1 gene variants in Chinese individuals with ID and evaluate the pathogenicity of the detected variants. Methods: Whole exome sequencing (WES) was performed on 113 patients diagnosed with ID. In the study, two de novo variants in SYNGAP1 were identified. Sanger sequencing was used to confirm these variants. Minigene assays were used to verify whether the de novo intronic variant in SYNGAP1 influenced the normal splicing of mRNA. Results: Two de novo heterozygous pathogenic variants in SYNGAP1, c.333del and c.664-2A>G, were identified in two ID patients separately. The c.333del variant has been reported previously as a de novo finding in a child with ID, while the c.664-2A>G variant was novel de novo intronic variant, which has not been reported in the literature. Functional studies showed that c.664-2A>G could cause aberrant splicing, resulting in exon 7 skipping and a 16bp deletion within exon 7. Conclusion: We identified two de novo pathogenic heterozygous variants in SYNGAP1 in two patients with ID, among which the c.664-2A>G variant was a novel de novo pathogenic variant. Our findings further enrich the variant spectrum of the SYNGAP1 gene and provide a research basis for the genetic diagnosis of ID.

Vacuum sealing drainage combined with eggshell-like debridement antibiotic-loaded calcium sulphate for calcaneal osteomyelitis.

BACKGROUND: To compare the clinical efficacy of vacuum sealing drainage, eggshell-like debridement combined with antibiotic calcium sulphate implantation and conventional debridement combined with antibiotic calcium sulphate implantation in the treatment of calcaneal osteomyelitis. METHODS: Sixty-six patients with calcaneal osteomyelitis who were treated in our department between January 2017 and August 2021 were included in this study. Thirty-one patients underwent VSD and eggshell-like debridement combined with antibiotic calcium sulphate implantation. Thirty-five patients underwent conventional debridement combined with antibiotic calcium sulphate implantation. The inflammatory markers, operation time, wound healing time, hospital stay, full weight bearing time after operation, recurrence rate of infection, complications, and American Orthopedic Foot and Ankle Society (AOFAS) scores were compared between the two groups. RESULTS: The operation time and full weight bearing time after operation of observation group were longer than that of control group. Compared with preoperative results, WBC, ESR, CRP and PCT in both groups were significantly decreased at 14 days after operation, and there was no statistical significance between the two groups. The wound healing time and hospital stay in the observation group were shorter than those in the control group (P < 0.05). There were four patients with aseptic exudation in the observation group and ten patients with aseptic exudation in the control group, and the wounds healed well after multiple dressing changes. Seven patients in the observation group underwent secondary bone grafting due to bone defects, and four patients in the control group received secondary bone grafting due to bone defects. In the observation group, three patients received debridement combined with antibiotic calcium sulphate implantation again due to recurrent infection, compared with seven patients in the control group. One year after operation, the observation group had a better AOFAS scores than the control group, especially in terms of foot function (P < 0.05). CONCLUSION: Compared with conventional debridement and antibiotic calcium sulphate implantation, VSD and eggshell-like debridement combined with antibiotic calcium sulphate implantation in the treatment of calcaneal osteomyelitis can shorten the wound healing and hospital stay of patients, reduce postoperative aseptic exudation complications and infection recurrence rate, and better preserve the foot function, which is a simple and effective method.

Starch Properties of Roasting Rice from Naturally High-Resistant Starch Rice Varieties.

This study investigates the effects of moisture content control on the characteristics, properties, and in vitro starch digestion of roasted rice powder made from natural high-resistant starch (RS) rice varieties. The results demonstrate that adjusting the moisture content before roasting significantly affects the RS content of the roasted rice powder. Among various moisture levels tested, the addition of 15% water (rice-to-water ratio of 85:15) before roasting resulted in the highest RS content, reaching 22.61%. Several key parameters of the rice samples before and after optimal moisture control were analyzed, including thermal stability, chain length distribution, volatile flavor composition, and scanning electron microscopy. Additionally, in vitro digestion properties were measured. The findings revealed that the volatile flavor compounds in the high-RS roasted rice significantly increased compared to non-roasted rice. Moreover, the thermal stability of the rice samples improved, and the chain length distribution exhibited significant changes. The water absorption and expansion properties were significantly lower in the high-RS roasted rice. Furthermore, the in vitro starch digestion of the roasted flour made from high-RS rice showed a significantly lower digestion rate compared to common rice, indicating a lower starch hydrolysis index in high-RS rice with the sbe-rs genotype. Overall, the roasting process of natural high-RS rice modifies its characteristics, increases the RS content, enhances the flavor, and results in a lower starch digestion rate compared to common rice. This study provides valuable data for the food industry to promote the application of high-RS rice varieties with mutations in the SBEIIb gene, such as Youtangdao2 (YTD2).

Melatonin activates the OsbZIP79-OsABI5 module that orchestrates nitrogen and ROS homeostasis to alleviate nitrogen-limitation stress in rice.

Melatonin (Mel) has previously been reported to effectively alleviate nitrogen-limitation (N-L) stress and thus increase nitrogen-use efficiency (NUE) in several plants, but the underlying mechanism remains obscure. Here, we revealed that OsbZIP79 (BASIC LEUCINE ZIPPER 79) is transcriptionally activated under N-L conditions, and its expression is further enhanced by exogenous Mel. By the combined use of omics, genetics, and biological techniques, we revealed that the OsbZIP79-OsABI5 (ABSCISIC ACID INSENSITIVE 5) module stimulated regulation of reactive oxygen species (ROS) homeostasis and the uptake and metabolism of nitrogen under conditions of indoor nitrogen limitation (1/16 normal level). OsbZIP79 activated the transcription of OsABI5, and OsABI5 then bound to the promoters of target genes, including genes involved in ROS homeostasis and nitrogen metabolism, activating their transcription. This module was also indispensable for upregulation of several other genes involved in abscisic acid catabolism, nitrogen uptake, and assimilation under N-L and Mel treatment, although these genes were not directly transactivated by OsABI5. Field experiments demonstrated that Mel significantly improved rice growth under low nitrogen (L-N, half the normal level) by the same mechanism revealed in the nitrogen-limitation study. Mel application produced a 28.6% yield increase under L-N and thus similar increases in NUE. Also, two OsbZIP79-overexpression lines grown in L-N field plots had significantly higher NUE (+13.7% and +21.2%) than their wild types. Together, our data show that an OsbZIP79-OsABI5 module regulates the rice response to N insufficiency (N limitation or low N), which is important for increasing NUE in rice production.

Correction method of the fluorescence intensity of petroleum hydrocarbons in different soil types based on resonance scattering spectroscopy.

Soil types has an obvious impact influence on the fluorescence intensity of soil petroleum hydrocarbons. To reduce the interference caused by soil types, this paper proposes a calibration method using resonance scattering spectroscopy. To establish the correction method, 100 g/kg crude oil samples from six soil types were prepared. The mission and resonance scattering spectrum under 280 nm excitation were measured for all samples. The results showed that the fluorescence spectra and resonance scattering spectra of soil crude oil vary with different soil types. And the fluorescence peak intensity and the resonance scattering peak intensity at 360 nm of soil petroleum hydrocarbons are highly correlated in different soil types. The fluorescence peak intensity at 360 nm was divided by the resonance scattering light intensity at 360 nm to obtain the corrected fluorescence intensity, which can effectively reduce the influence of soil type on fluorescence intensity. The feasibility of correction method was further verified for different types and concentrations of soil crude oil. The results showed better linearity between the fluorescence intensity and the concentration of Petroleum Hydrocarbons after the correction (with a correlation coefficient R2 of 0.96) than before the correction (with R2 of 0.72), the mean relative prediction error of all samples decreased from 31.92 % to 4.71 % after correction. The research can provide theoretical basis and technical support for the accurate and rapid detection of Petroleum Hydrocarbons in soil by fluorescence spectroscopy.

A Method of Water COD Retrieval Based on 1D CNN and 2D Gabor Transform for Absorption-Fluorescence Spectra.

Chemical Oxygen Demand (COD) is one of the indicators of organic pollution in water bodies. The rapid and accurate detection of COD is of great significance to environmental protection. To address the problem of COD retrieval errors in the absorption spectrum method for fluorescent organic matter solutions, a rapid synchronous COD retrieval method for the absorption-fluorescence spectrum is proposed. Based on a one-dimensional convolutional neural network and 2D Gabor transform, an absorption-fluorescence spectrum fusion neural network algorithm is developed to improve the accuracy of water COD retrieval. Results show that the RRMSEP of the absorption-fluorescence COD retrieval method is 0.32% in amino acid aqueous solution, which is 84% lower than that of the single absorption spectrum method. The accuracy of COD retrieval is 98%, which is 15.3% higher than that of the single absorption spectrum method. The test results on the actual sampled water spectral dataset demonstrate that the fusion network outperformed the absorption spectrum CNN network in measuring COD accuracy, with the RRMSEP improving from 5.09% to 1.15%.

Genetic analysis and prenatal diagnosis of recessive dystrophic epidermolysis bullosa caused by compound heterozygous variants of the COL7A1 gene in a Chinese family.

Background: Dystrophic epidermolysis bullosa (DEB) is an incurable and inherited skin disorder mainly caused by mutations in the gene encoding type VII collagen (COL7A1). The purpose of this study was to identify the causative genetic variants and further perform genetic diagnosis in a Chinese family affected by DEB. Methods: High-throughput sequencing was performed to analyze the genetic skin disorder-related genes of parents of the proband, and the variants were further confirmed in the other members by Sanger sequencing. Sanger sequencing, karyotype analysis, and chromosomal microarray analysis (CMA) were used together for prenatal diagnosis after the second pregnancy. The phenotype of the fetus was tracked after the diagnosis and induction of labor. Moreover, skin and muscle pathological examination and whole-exome sequencing (WES) of the skin and muscle tissue of the induced fetus were performed. Results: Here, we determined two heterozygous variants of the COL7A1 gene that contributed to the autosomal recessive DEB (RDEB) in the family, i.e., a novel pathogenic variant (c.8335G > T, p.E2779*) and a likely pathogenic variant (c.7957G > A, p.G2653R). Sanger sequencing of amniotic fluid cells showed that the fetus carried the above two compound heterozygous variants, and the karyotype analysis and CMA results showed no abnormality. The clinical phenotype and pathological results of the induced fetus were consistent with the characteristics of DEB. Further, WES analysis also confirmed a novel compound heterozygous variation in COL7A1, consisting of two variants, namely, c.8335G > T and c.7957G > A in the fetus. Conclusion: This study expands the spectrum of disease-causing variants of COL7A1 and provides a theoretical basis for diagnosis, genetic counseling, and prognosis of families affected by RDEB.

The Association of Peripheral T Lymphocyte Subsets Disseminated Infection by Mycobacterium Tuberculosis in HIV-Negative Patients: A Retrospective Observational Study.

Background and Objective: This study was performed to investigate the association of peripheral T lymphocyte subsets with disseminated infection (DI) by Mycobacterium tuberculosis (MTB) in HIV-negative patients. Methods and Materials: The study included 587 HIV-negative tuberculosis (TB) patients. Results: In TB patients with DI, the proportion of CD4+ T cells decreased, the proportion of CD8+ T cells increased, and the ratio of CD4+/CD8+ T cells decreased. According to univariate analysis, smoking, alcohol consumption, rifampicin-resistance, retreatment, and high sputum bacterial load were linked to lower likelihood of developing MTB dissemination. Multivariate analysis indicated that after adjustment for alcohol use, smoking, retreatment, smear, culture, rifampicin-resistance, and CD4+/CD8+, the proportion of CD8+ T cells (but not CD4+ T cells) was independently and positively associated with the prevalence of DI in HIV-negative pulmonary TB (PTB) patients. Conclusions: Examining T lymphocyte subsets is of great value for evaluating the immune function of HIV-negative TB patients, and an increase in the CD8+ T cell proportion may be a critical clue regarding the cause of DI in such patients.

Design of an Intervention and Education System for Children with Emotional Disorders Based on Semantic Analysis.

In this paper, a semantic analysis approach to children's emotional disorder intervention and education is thoroughly analyzed and discussed, and a corresponding educational system is designed for application in real life. This paper acquires video data by deploying a common camera acquisition and transforms, annotates, frames, and processes the data with the help of feature engineering methods. In addition, this paper proposes a fine-grained action decomposition strategy to solve the problem of extreme imbalance in the dataset to improve the performance of the model and proposes an iterative sampling data fusion strategy, which aims to integrate and fuse data from multiple sources to make them more effective and further improve the robustness and generalization ability of the model. Since it is difficult for families to improve the emotional management skills of migrant children, and it is also difficult to obtain professional help and support from the community or schools, it is important to take advantage of the professional strengths of social work to provide professional support for migrant children and their families. From the perspective of theoretical research, most of the existing studies focus on individual migrant children and cannot give global guidance from the perspective of the family system. The comparison results show that T-SVR trained using data from all subjects outperforms the inductive method based on individual training of trainees, validating the effectiveness of the proposed adaptive emotion recognition model. Therefore, from the perspective of system integration, it is important to explore social work interventions to improve the emotional management skills of migrant children. The system network structure design is determined according to the actual situation; then from the system requirements, the system is abstracted with the help of UML entity-relationship diagram, and the database table design is completed; so far, the overall system can be divided into independent functional modules, and the boundaries of each module and the participating roles are gradually clarified, and the detailed design within each functional module is illustrated by UML timing diagram and class diagram to clarify the classes used. Finally, the system is tested end-to-end to verify whether the results of the view layer meet the design guidelines, whether the system modules work together properly, and whether the functional development meets the requirements.

Histone demethylase KDM2A suppresses EGF-TSPAN8 pathway to inhibit breast cancer cell migration and invasion in vitro.

Metastasis is a major cause of breast cancer mortality and the current study found histone demethylase, KDM2A, expression to be negatively correlated with breast cancer metastasis. KDM2A knockdown greatly promoted migration and invasion of breast cancer cells. The histone demethylase activity of KDM2A downregulated EGF transcription and suppressed the EGF-TSPAN8 pathway. Inhibition of breast cancer cell migration was also dependent on the histone demethylase activity of KDM2A. A novel mechanism of KDM2A-suppression of the EGF-TSPAN8 pathway which inhibited breast cancer cell migration and invasion is reported.

OsSGT1 promotes melatonin-ameliorated seed tolerance to chromium stress by affecting the OsABI5-OsAPX1 transcriptional module in rice.

Chromium (Cr) pollution threatens plant development and growth. Application of melatonin (Mel) is emerging as an effective ally to resist stress, but how Mel ameliorates seed germination upon exposure to heavy metals is poorly understood. Here, we found (i) that seed priming with Mel considerably alleviated Cr stress during rice (Oryza sativa) seed germination and (ii) that germination performance was significantly improved in suppressor of the G2 allele of skp1 (OsSGT1) overexpression lines, while mutations of OsSGT1 and/or abscisic acid-insensitive 5 (OsABI5) noticeably abrogated such Mel-induced tolerance to Cr. Complementation assays suggested that the restored expression of OsSGT1 could not rescue the weak germination of sgt1-1abi5 under Cr stress, even upon Mel priming, but the expression of OsABI5 driven by the promoter of OsSGT1 significantly restored the Mel-ameliorated germination and the expression of ascorbate peroxidase 1 (OsAPX1) in sgt1-1abi5. Further analysis indicated that OsABI5 directly regulated the transcriptional expression of OsAPX1, whose encoding products promoted H2 O2 scavenging to maintain redox homeostasis, which is essential for germination. Collectively, this work demonstrates that OsSGT1 regulates OsABI5 to target OsAPX1, mediating the stimulatory effects of Mel on germination of Cr-stressed seeds, which provides a guide for the application of Mel in rice production.

Evaluation of a novel inhibitor of aspartate semialdehyde dehydrogenase as a potent antitubercular agent against Mycobacterium tuberculosis.

The in vitro activity of IMB-XMA0038, a novel inhibitor targeting Mycobacterial tuberculosis (Mtb) aspartate semialdehyde dehydrogenase, was evaluated. Minimum inhibitory concentrations (MICs) of IMB-XMA0038 were against 20 Mtb isolates, including H37Rv (ATCC 27294), ten clinical pan-sensitive isolates, and nine clinical multidrug-resistant (MDR) isolates. In addition, minimum bactericidal concentrations (MBCs) were also determined against the H37Rv and 6 MDR isolates (the background information is same as above in order). A model was generated to evaluate IMB-XMA0038 activity against dormant Mtb. The post-antibiotic effect (PAE), an important indicator of antimicrobial drug dosing schedules to obtain efficacy, was determined based on time required for regrowth of Mtb to 50% of the OD600max value after treatment with various concentrations of IMB-XMA0038 and INH. In addition, interactions between IMB-XMA0038 and other anti-tuberculosis drugs, measured using a checkerboard assay, revealed that IMB-XMA0038 MICs of 0.5-1 µg/mL could be achieved in combinations. Synergistic effects were observed for IMB-XMA0038 when used together with almost all other anti-tuberculosis drugs against most Mtb isolates. IMB-XMA0038 exhibited greater activity than rifampin against Mtb under hypoxic conditions, as reflected by CFU decreases of 1.1-log-unit versus 0.8-log-unit, respectively, for IMB-XMA0038 and rifampin concentrations of 4 × MIC. IMB-XMA0038-induced PAEs (9, 10, 11 days) were comparable to INH PAEs (10, 11, 12 days). These findings suggest that addition of IMB-XMA0038 to current therapeutic regimens could be useful to improve the efficacy of treatments for drug-resistant and drug-susceptible TB.

CD84 is a Suppressor of T and B Cell Activation during Mycobacterium tuberculosis Pathogenesis.

Interest in host-directed therapies as alternatives/adjuncts to antibiotic treatment has resurged with the increasing prevalence of antibiotic-resistant tuberculosis (TB). Immunotherapies that reinvigorate immune responses by targeting immune checkpoints like PD-1/PD-L1 have proved successful in cancer therapy. Immune cell inhibitory receptors that trigger Mycobacterium tuberculosis-specific immunosuppression, however, are unknown. Here, we show that the levels of CD84, a SLAM family receptor, increase in T and B cells in lung tissues from M. tuberculosis-infected C57BL/6 mice and in peripheral blood mononuclear cells (PBMCs) from pulmonary TB patients. M. tuberculosis challenge experiments using CD84-deficient C57BL/6 mice suggest that CD84 expression likely leads to T and B cell immunosuppression during M. tuberculosis pathogenesis and also plays an inhibitory role in B cell activation. Importantly, CD84-deficient mice showed improved M. tuberculosis clearance and longer survival than M. tuberculosis-infected wild-type (WT) mice. That CD84 is a putative M. tuberculosis infection-specific inhibitory receptor suggests it may be a suitable target for the development of TB-specific checkpoint immunotherapies. IMPORTANCE Immune checkpoint therapies, such as targeting checkpoints like PD-1/PD-L1, have proved successful in cancer therapy and can reinvigorate immune responses. The potential of this approach for treating chronic infectious diseases like TB has been recognized, but a lack of suitable immunotherapeutic targets, i.e., immune cell inhibitory receptors that trigger immunosuppression specifically during Mycobacterium tuberculosis pathogenesis, has limited the application of this strategy in the development of new TB therapies. Our focus in this study was to address this gap and search for an M. tuberculosis-specific checkpoint target. Our results suggest that CD84 is a putative inhibitory receptor that may be a suitable target for the development of TB-specific checkpoint immunotherapies.