Engineered exosomes: a potential therapeutic strategy for septic cardiomyopathy.

Septic cardiomyopathy, a life-threatening complication of sepsis, can cause acute heart failure and carry a high mortality risk. Current treatments have limitations. Fortunately, engineered exosomes, created through bioengineering technology, may represent a potential new treatment method. These exosomes can both diagnose and treat septic cardiomyopathy, playing a crucial role in its development and progression. This article examines the strategies for using engineered exosomes to protect cardiac function and treat septic cardiomyopathy. It covers three innovative aspects: exosome surface modification technology, the use of exosomes as a multifunctional drug delivery platform, and plant exosome-like nanoparticle carriers. The article highlights the ability of exosomes to deliver small molecules, proteins, and drugs, summarizing several RNA molecules, proteins, and drugs beneficial for treating septic cardiomyopathy. Although engineered exosomes are a promising biotherapeutic carrier, they face challenges in clinical application, such as understanding the interaction mechanism with host cells, distribution within the body, metabolism, and long-term safety. Further research is essential, but engineered exosomes hold promise as an effective treatment for septic cardiomyopathy.

Eosin Y Post-Decorated Metal-Organic Framework as a Selectivity Regulator for the Alcohols Oxidation.

The selective oxidation of alcohols into aldehydes is a basic and significant procedure, with great potential for scientific research and industrial applications. However, as an important factor in the C(sp3)-H activation process, high selectivity is generally difficult to achieve due to the fact that the more easily activated properties of aldehydes are compared to alcohols. Herein, by the ingenious decoration of eosin Y into a Zr-based metal-organic framework (MOF-808), EY@MOF-808 was prepared as a selectivity regulator for the aerobic oxidation of the benzyl alcohols into corresponding aldehydes, possessing applicability for the benzylic alcohols with various substituents. By anchoring eosin Y on Zr6O4(OH)4 clusters of MOF-808 and maintaining open metal nodes with selective binding effects, the benzyl alcohol substrates were selectively coordinated to the unsaturated metal clusters adjacent to eosin Y, which ensured that the excited eosin Y rapidly activated substrates to generate carbon radicals by the hydrogen atom transfer (HAT) process. The rapid electron transfer (ET) simultaneously produced reactive oxygen species (O2•-) and then a combination of both to further promote the generation of benzaldehydes. The weak interaction of benzaldehydes with the skeleton allowed it to dissociate rapidly, thus preventing overoxidation. Under the catalysis of EY@MOF-808, the selectivity of various benzaldehydes was more than 99%. In contrast, eosin Y gave only benzoic acid products under the same conditions, which demonstrated the superiority of regulatory selectivity of EY@MOF-808. Taking advantage of the heterogeneity of the MOF, EY@MOF-808 was recycled four times without a decrease in its selectivity and avoided the quenching effect of eosin Y. The organic functional units postdecorated MOF-based photocatalyst strategy exhibits a promising new perspective approach to sustainably regulating the selectivity of inert oxidation.

An improved method of local coloring in vertical-slot fishways to enhance the fish migration effect of grass carp.

Vertical-slot fishway (VSF) has been used in many water conservancy projects to restore the river connectivity. A high-quality fishway project should facilitate fish to discovering the exit and passing through, avoiding to long stay in the fishway and delay the migration. Current research on fishway engineering has not yielded an expected passing ratio of fish migration, and it is therefore of great significance to further study the assisting effect of VSF in fish migration. To begin with, we preliminarily determined the attractive and repelling colors of grass carps based on their swimming behavior in a static water pool configured with local colors. Combined with the migration route of the grass carp in a VSF pool without local coloring, four local coloring cases were designed. Based on the camera results of the four experimental local coloring cases, a comparative analysis was conducted with the blank control group frame by frame. This was followed by the statistics of the number of successfully migrated grass carps and their total completion time. On that basis, the assisting effect of VSF in fish migration under the four cases was evaluated in terms of the reduction rate of migration route length, the reduction rate of completion time, and the improvement rate of passing ratio. The research outcomes indicated that green and blue act as attractive colors while yellow and red serve as repelling colors for grass carp. Adding colors to the training wall and dividing wall in the VSF pool, the migration route of grass carp was appropriately adjusted, alongside a shortened completion time and an improved passing ratio. Of the four local coloring cases, the recommended case showed a significant effect on migration route, with more concentrated moving trajectories and shortened route length. Typically, the migration route length decreased by 26%, and the frequency of fish long staying at the junction between the training wall and dividing wall was markedly reduced, as well as the frequency of fish swimming along the water flow from upstream to downstream. The completion time was shortened by 26%, and the passing ratio was enhanced by 44%. The approach of combining local coloring with fish behavior and fishway hydraulics in the pool surpassed the method that optimizes the fishway design only from the fishway hydraulics. The improved method greatly shortened the migration route length, reduced the completion time, and significantly improved the passing ratio of fish passage objects in the VSF. The present research mainly focuses on using model experiments to evaluate the local coloring cases. In the future studies, we will configure local colors to the sidewalls of on-site fishways using environmentally friendly paint or colored organic glass panels. With the monitoring results of the completion time and passing ratio of fish passage objects, the recommended case can be further verified and optimized, thereby providing a more reasonable and feasible local coloring case for assisting fish migration in the VSF project.

People-Oriented Nursing Mode on the Negative Emotions and Psychological Status of Patients with Bladder Cancer.

Background: We aimed to investigate the clinical application effect of people-oriented nursing model on the negative emotions and psychological conditions of patients with bladder cancer. Methods: Eighty patients with bladder cancer were enrolled from January 2020 to January 2022 in the Second Affiliated Hospital of Qiqihar Medical University Heilongjiang, Province, China. The patients were randomly divided into the control group, each group consisted of 40 patients (conventional nursing mode) and the experimental group (people-oriented nursing mode) according to the admission time. The differences of the anxiety, depression and quality of life scores at the time of admission and discharge were compared between the two groups. Results: There was statistically significant differences in the Self-Rating Anxiety Scale (SAS) and Self-rating depression scale (SDS) score within each group of patients and between the two groups at the time of admission and discharge, respectively (P=0.001). In addition, there was a statistically significant difference in the scores at discharge, and the scores of the patients in the experimental group were better than those in the control group. There was a statistically significant difference in the scores at discharge, and the scores of the experimental group were lower than those of the control group P<0.001). After comparing the overall scores of admission and discharge of the two groups of patients, the differences were statistically significant, and the scores at discharge were better improved than those at admission were. Conclusion: The people-oriented nursing model could relieve the negative emotions, relieve pain and improve the life quality of patients with bladder cancer.

Cellulose-based adsorbent using in mercury detection and removal from water via an efficient grafting strategy of fluorometric sensors by click reaction.

Mercury pollution in waters attracts lots of attention due to its serious toxicity and high bioenrichment and many efforts have been devoted in the development of adsorbents for mercury detection and removal. Herein, a cellulose-based adsorbent Cell-TriA-HQ is functionalized with quinoline fluorophore by covalent immobilization through "Click reaction" with high yield. In addition to the admirable adsorptive performance, the prepared adsorbent exhibits excellent selectivity and sensitivity towards Hg (II) in water that the detection limit for Hg (II) is determined to be as low as 1.92 × 10-7 M. The sensitive fluorescence enhancement response is considered to be resulted from the inhibition of photo-induced electron transfer between triazole and quinoline groups and the reinforcement of structural rigidity. The easy manipulation along with excellent performance of adsorption capacity, detective ability and reusability for the multifunctional adsorbent makes it potential in mercury monitoring and removal from aqueous solutions in the field of water treatment.

Construction of Hierarchical Conductive Networks for LiNi0.8Mn0.1Co0.1O2 Cathode toward Stable Cycling at High Areal Mass Loadings.

Realizing high-performance thick electrodes is considered as a practical strategy to promote the energy density of lithium-ion batteries. However, establishing effective transport pathways for both lithium-ions and electrons in a thick electrode is very challenging. This study develops a hierarchical conductive network structure for constructing high-performance NMC811 (LiNi0.8Mn0.1Co0.1O2) cathode toward stable cycling at high areal mass loadings. The hierarchical conductive networks are composed of a Li+/e- mixed conducting interface (lithium polyacrylate/hydroxyl-functionalized multiwalled carbon nanotubes) on NMC811 particles, and a segregated network of single-walled carbon nanotubes in the electrode, without any additional binders or carbon black. Such strategy endows the NMC811 cathode (up to 250 µm and 50 mg cm-2) with low porosity/tortuosity, ultrahigh Li+/e- conductivities and excellent mechanical property at low carbon nanotube content (1.8 wt%). It significantly improves the electrochemical reaction homogeneity along the electrode depth, meanwhile effectively inhibits the side reactions at the electrode/electrolyte interface and cracks in the NMC particles during cycling. This work emphasizes the crucial role of the electronic/ionic cooperative transportation in the performance deterioration of thick cathodes, and provide guidance for architecture optimization and performance improvement of thick electrodes toward practical applications, not just for the NMC811 cathode.

Clinical observation of ultraviolet therapy combined with autologous platelet-rich plasma in the treatment of chronic refractory wounds.

Refractory wounds present complex and serious clinical dilemmas in plastic and reconstructive surgeries. Currently, there are no standard guidelines for the treatment of refractory wounds. To observe the clinical effects of ultraviolet (UV) therapy combined with autologous platelet-rich plasma (PRP) on chronic refractory wounds. Between January 2021 and December 2022, 60 inpatients with chronic refractory wounds were enrolled. Twenty patients were assigned to each of control groups 1 and 2 and treatment group according to whether they received PRP or UV treatment. All the patients underwent thorough debridement. Control group 2 received UV radiation. The treatment group underwent UV radiation combined with PRP gel covering the wound. Control group 1 underwent routine dressing changes after surgery, followed by skin grafting or skin key transfer if needed. One month later, we observed the wound healing in the two groups. After 2-4 PRP gel treatments, the wounds of patients in the treatment group healed. The healing time was 25.25 ± 4.93 days, and the dressings were changed 4.15 ± 3.30 times, both of which were better outcomes than in both control groups. In the treatment group, epidermal growth factor (EGF), insulin-like growth factor (IGF), platelet-derived growth factor (PGF), and transforming growth factor ß (TGF-ß) were slightly higher, and the concentration of vascular endothelial growth factor (VEGF) was significantly higher than in the control group (p < 0.05). PRP combined with UV therapy significantly increased the concentration of wound growth factors, accelerated wound healing, shortened treatment time, reduced treatment costs, and alleviated pain in patients.

Transient pulmonary and gastric bleeding after iopamidol administration in a patient with marginal zone lymphoma: a case report.

BACKGROUND: Iopamidol is a non-ionic, water-soluble iodine contrast agent that is considered safe for intravenous or intra-arterial administration and is widely used both in the general population and in patients undergoing oncological treatment. While adverse reactions to iopamidol have been documented, to date, no pulmonary and gastric hemorrhages induced by iopamidol have been reported in oncology patients. We report the first case of this complication. CASE PRESENTATION: We report the case of a 60-year-old woman with marginal zone lymphoma who was receiving antineoplastic therapy. As part of the investigation for the condition, she underwent chest enhancement CT with iopamidol. Shortly thereafter(within five minutes), she experienced hemoptysis and hematemesis. She was intubated and admitted to the intensive care unit. Pre- and post-contrast images demonstrated the course of the hemorrhage. Flexible bronchoscopy and gastroscopy on the following day showed no active bleeding, and the patient recovered completely after antiallergy treatment. We speculate that contrast-induced hypersensitivity was the most likely cause of the transient pulmonary and gastric bleeding. CONCLUSION: Although rare, the complications of iopamidol, which may cause allergic reactions in the lungs and stomach, should be considered.

Keratin 6A (KRT6A) promotes radioresistance, invasion, and metastasis in lung cancer via p53 signaling pathway.

BACKGROUND: It is reported that the incidence rate and mortality of lung cancer are very high. Therefore, early diagnosis and identification of specific biomarkers are crucial for the clinical treatment of lung cancer. This study aims to comprehensively investigate the prognostic significance of KRT6A in human lung cancer. METHODS: The GEO2R online tool was utilized to analyze the differential expression of mRNA between lung carcinoma tissues and radioresistant tissues in the GSE73095 and GSE197236 datasets. DAVID database was used to perform GO and KEGG enrichment analyses on target genes. The Kaplan-Meier plotter tool was used to analyze the impact of key messenger ribonucleic acid on the survival status of lung cancer. In addition, quantitative real-time polymerase chain reaction (qPCR) was used to investigate the impact of key genes on the phenotype of lung cancer cells. After the knockout, we conducted cell migration and CCK-8 experiments to detect their effects on cell proliferation and invasion. RESULTS: 40 differentially expressed genes (DEGs) were chosen from GSE73095 and 118 DEGs were chosen from GSE197236. Kaplan-Meier map analysis showed that the overall cancer survival rate of the high-expression KRT6A group was higher than that of the low-expression group (P < 0.05). Besides, cell experiments have shown that when the KRT6A gene is downregulated, the proliferation and invasion ability of lung cancer cells is weakened. CONCLUSIONS: Our research concluded that KRT6A may take part in the radioresistance and progression of lung cancer and can be a potential biomarker for lung cancer patients.

Explainable machine learning for early predicting treatment failure risk among patients with TB-diabetes comorbidity.

The present study aims to assess the treatment outcome of patients with diabetes and tuberculosis (TB-DM) at an early stage using machine learning (ML) based on electronic medical records (EMRs). A total of 429 patients were included at Chongqing Public Health Medical Center. The random-forest-based Boruta algorithm was employed to select the essential variables, and four models with a fivefold cross-validation scheme were used for modeling and model evaluation. Furthermore, we adopted SHapley additive explanations to interpret results from the tree-based model. 9 features out of 69 candidate features were chosen as predictors. Among these predictors, the type of resistance was the most important feature, followed by activated partial throm-boplastic time (APTT), thrombin time (TT), platelet distribution width (PDW), and prothrombin time (PT). All the models we established performed above an AUC 0.7 with good predictive performance. XGBoost, the optimal performing model, predicts the risk of treatment failure in the test set with an AUC 0.9281. This study suggests that machine learning approach (XGBoost) presented in this study identifies patients with TB-DM at higher risk of treatment failure at an early stage based on EMRs. The application of a convenient and economy EMRs based on machine learning provides new insight into TB-DM treatment strategies in low and middle-income countries.

The m6A demethylase fat mass and obesity-associated protein mitigates pyroptosis and inflammation in doxorubicin-induced heart failure via the toll-like receptor 4/NF-κB pathway.

Background: Doxorubicin (Dox) can induce cardiotoxicity, thereby restricting the utility of this potent drug. Herein, the study ascertained the mechanism of the N6-methyladenosine (m6A) demethylase fat mass and obesity-associated protein (FTO) in pyroptosis and inflammation during Dox-induced heart failure (HF). Methods: Serum samples were collected from HF patients for detection of the expression of FTO and toll-like receptor 4 (TLR4). Dox-treated H9C2 cardiomyocytes were chosen for in vitro HF modeling, followed by measurement of FTO and TLR4 expression. Cardiomyocytes were detected for viability, apoptosis, spatial distribution of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), and the levels of lactic dehydrogenase, inflammatory factors, oxidative stress markers, and pyroptosis-related proteins. The m6A levels of mRNA were examined. RNA immunoprecipitation (RIP) and mRNA stability measurement were used to determine mRNA and protein expression, and RNA m6A dot blot and methylated-RIP assay were performed to detect m6A methylation levels. The expression of p-NF-κB p65 and p-IκB-α was measured by western blotting. Results: In the serum of HF patients, FTO was elevated while TLR4 was decreased. Dox treatment reduced FTO expression and increased m6A methylation levels and TLR4 expression in H9C2 cells. Overexpression of FTO and knockdown of TLR4 reduced apoptosis, cytotoxicity, inflammation, pyroptosis, oxidative stress, NLRP3 co-localization, and fluorescence intensity in Dox-induced H9C2 cells. Mechanistically, FTO resulted in reduced binding activity of YTHDF1 to TLR4 mRNA via m6A demethylation of TLR4, thus declining TLR4, p-NF-κB p65, and p-IκB-α expression. TLR4 knockdown counteracted the effects of FTO knockdown on Dox-induced H9C2 cells. Conclusions: FTO alleviated Dox-induced HF by blocking the TLR4/NF-κB pathway.

A novel ratiometric fluorescent probe with high selectivity for lysosomal nitric oxide imaging.

Nitric oxide (NO) plays critical roles in both physiology and pathology, serving as a significant signaling molecule. Recent investigations have uncovered the pivotal role of lysosome as a critical organelle where intracellular NO exists and takes function. In this study, we developed a novel ratiometric fluorescent probe called XL-NO and modified it with a morpholine unit, which followed the intramolecular charge transfer (ICT) mechanism. The probe could detect lysosomal nitric oxide with high selectivity and sensitivity. The probe XL-NO contained a secondary amine moiety that could readily react with NO in lysosomes, leading to the formation of the N-nitrosation product. The N-nitroso structure enhanced the capability in push-pull electron, which obviously led to the change of fluorescence from 621 nm to 521 nm. In addition, XL-NO was discovered to have some evident advantages, such as significant ratiometric signal (I521/I621) change, strong anti-interference ability, good biocompatibility, and a low detection limit (LOD = 44.3 nM), which were crucial for the detection of lysosomal NO. To evaluate the practical application of XL-NO, NO imaging experiments were performed in both living cells and zebrafish. The results from these experiments confirmed the feasibility and reliability of XL-NO for exogenous/endogenous NO imaging and lysosome targeting.

Strong, tough, and elastic poly(vinyl alcohol)/polyacrylamide DN hydrogels based on the Hofmeister effect for articular cartilage replacement.

Traditional hydrogels are usually weak and brittle, which limit their application in articular cartilage replacement because cartilage is generally strong, tough, and elastic in nature. Therefore, it is highly desirable to construct hydrogels to mimic the mechanical properties of the native articular cartilage. Herein, in this work, poly(vinyl alcohol)/polyacrylamide (PVA/PAM) DN hydrogels were prepared by in situ polymerization, which were then treated with Hofmeister series ions (Cit3-, SO42-, and Cl-) to achieve H-PVA/PAM DN hydrogels. Among the three Hofmeister ions, the DN hydrogel treated with Cit3- (named PVA/PAM-Cit) showed the densest microstructure and the highest crystallinity degree. In this context, PVA/PAM-Cit exhibited a tensile strength of 18.9 ± 1.6 MPa, a compressive strength of 102.3 ± 7.9 MPa, a tensile modulus of 10.6 ± 2.1 MPa, a compressive modulus of 8.9 ± 0.8 MPa, and a roughness of 66.2 ± 4.2 MJ m-3, respectively, which were the highest strength and modulus, and the second highest toughness when compared with those of the reported PVA and PVA based DN hydrogels so far. It also showed an extreme high elasticity, which could maintain a stress of 99.2% after 500 cycles of fatigue testing. Additionally, PVA/PAM-Cit can promote the adhesion, spreading and proliferation of chondrocytes. These results verify that such a strong, tough, and elastic hydrogel could be a novel candidate material for articular cartilage replacement.

A Glutathione Peroxidase-Mimicking Nanozyme Precisely Alleviates Reactive Oxygen Species and Promotes Periodontal Bone Regeneration.

The use of oxidoreductase nanozymes to regulate reactive oxygen species (ROS) has gradually emerged in periodontology treatments. However, current nanozymes for treating periodontitis eliminate ROS extensively and non-specifically, ignoring the physiological functions of ROS under normal conditions, which may result in uncontrolled side effects. Herein, using the MIL-47(V)-F (MVF) nanozyme, which mimics the function of glutathione peroxidase (GPx), it is proposed that ROS can be properly regulated by specifically eliminating H2 O2 , the most prominent ROS. Through H2 O2 elimination, MVF contributes to limiting inflammation, regulating immune microenvironment, and promoting periodontal regeneration. Moreover, MVF stimulates osteogenic differentiation of periodontal stem cells directly, further promoting regeneration due to the vanadium in MVF. Mechanistically, MVF regulates ROS by activating the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) pathway and promotes osteogenic differentiation directly through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. A promising periodontitis therapy strategy is presented using GPx-mimicking nanozymes through their triple effects of antioxidation, immunomodulation, and bone remodeling regulation, making nanozymes an excellent tool for developing precision medicine.

[Health Benefit Assessment of Coal-to-electricity Policy on PM2.5 Pollution in Beijing-Tianjin-Hebei Region].

To accurately assess the health benefits of the coal-to-electricity policy during the heating period in the Beijing-Tianjin-Hebei(BTH) Region, the premature deaths caused by PM2.5 before and after the implementation of the coal-to-electricity policy during the heating period in each district and county of the BTH Region were estimated, and the corresponding health loss values were calculated using the willingness to pay method. The results showed that the implementation of the coal-to-electricity policy in the BTH Region brought 1745 cases(95% CI:1443-1907) of health benefits and 2.38 billion yuan(95% CI:1.45-3.06) in economic benefits. In Beijing, Tianjin, and Hebei there were 495 cases(95% CI:436-554), 296 cases(95% CI:238-354), and 954 cases(95% CI:693-1076) of health benefits, respectively. The economic benefits were 0.35 billion yuan(95% CI:0.30-0.39), 0.33 billion yuan(95% CI:0.27-0.40), and 1.70 billion yuan(95% CI:0.88-2.28), respectively, accounting for 0.01%, 0.02%, and 0.04% of GDP in each region. The number of premature deaths due to COPD, LC, ALRI, IHD, and STROKE decreased by 187 cases(95% CI:165-224), 318 cases(95% CI:178-458), 193 cases(95% CI:115-204), 506 cases(95% CI:232-780), and 542 cases(95% CI:463-621), respectively. Areas with relatively high environmental PM2.5 concentrations and concentrated population-intensive pollution emissions can achieve significant health and economic benefits.

New understandings of the genetic regulatory relationship between non-coding RNAs and m6A modification.

One of the most frequent epigenetic modifications of RNA in eukaryotes is N6 methyladenosine (m6A), which is mostly present in messenger RNAs. Through the influence of several RNA processing stages, m6A modification is a crucial approach for controlling gene expression, especially in cancer progression. It is universally acknowledged that numerous non-coding RNAs (ncRNAs), such as microRNAs, circular RNAs, long non-coding RNAs, and piRNAs, are also significantly affected by m6A modification, and the complex genetic regulatory relationship between m6A and ncRNAs plays a pivotal role in the development of cancer. The connection between m6A modifications and ncRNAs offers an opportunity to explore the oncogene potential regulatory mechanisms and suggests that m6A modifications and ncRNAs could be vital biomarkers for multiple cancers. In this review, we discuss the mechanisms of interaction between m6A methylation and ncRNAs in cancer, and we also summarize diagnostic and prognostic biomarkers for clinical cancer detection. Furthermore, our article includes some methodologies for identifying m6A sites when assessing biomarker potential.

A motion characteristics modeled angular position sensor by nonlinear transfer of differential capacitance for miniaturized scanning mirrors.

In this paper, an angular position sensor (APS) designed for a resonant miniaturized scanning mirror (M-SM) is presented. The APS operates based on the principle of differential variable capacitance, significantly expanding the detectable bandwidth from a few hertz to several kilohertz. By modeling the motion characteristics, the sampling rates of the biaxial scanning angles are 1473.6 times and 539.4 times higher than those of conventional sensors. Initially, the motion characteristics model is presented as a simple harmonic motion, converting sampled capacitance into continuous capacitance. Subsequently, the nonparallel state of the M-SM and sensor is transformed into a parallel state through the space coordinate system transformation. Furthermore, a 2D nonlinear angle transfer function is developed to convert the differential capacitance into an angle, thereby mitigating the nonlinear errors resulting from large angles. Achieving an accuracy better than 0.014°, the measuring range expands from ±0.5729° (±10 mrad) to ±5.026° ( ± 87 mrad). Additionally, the capturing mode and tracking mode are proposed to monitor real-time angular changes of the M-SM with an accuracy of 0.017°. High-precision APSs have enhanced beam pointing accuracy and resolution and can thereby be used to advance the development of laser components, including light detection and ranging (LiDAR).

Integrated Transcriptomic and Proteomic Analyses of Low-Nitrogen-Stress Tolerance and Function Analysis of ZmGST42 Gene in Maize.

Maize (Zea mays L.) is one of the major staple crops providing human food, animal feed, and raw material support for biofuel production. For its growth and development, maize requires essential macronutrients. In particular, nitrogen (N) plays an important role in determining the final yield and quality of a maize crop. However, the excessive application of N fertilizer is causing serious pollution of land area and water bodies. Therefore, cultivating high-yield and low-N-tolerant maize varieties is crucial for minimizing the nitrate pollution of land and water bodies. Here, based on the analysis of the maize leaf transcriptome and proteome at the grain filling stage, we identified 3957 differentially expressed genes (DEGs) and 329 differentially abundant proteins (DAPs) from the two maize hybrids contrasting in N stress tolerance (low-N-tolerant XY335 and low-N-sensitive HN138) and screened four sets of low-N-responsive genes and proteins through Venn diagram analysis. We identified 761 DEGs (253 up- and 508 down-regulated) specific to XY335, whereas 259 DEGs (198 up- and 61 down-regulated) were specific to HN138, and 59 DEGs (41 up- and 18 down-regulated) were shared between the two cultivars under low-N-stress conditions. Meanwhile, among the low-N-responsive DAPs, thirty were unique to XY335, thirty were specific to HN138, and three DAPs were shared between the two cultivars under low-N treatment. Key among those genes/proteins were leucine-rich repeat protein, DEAD-box ATP-dependent RNA helicase family proteins, copper transport protein, and photosynthesis-related proteins. These genes/proteins were involved in the MAPK signaling pathway, regulating membrane lipid peroxidation, and photosynthesis. Our results may suggest that XY335 better tolerates low-N stress than HN138, possibly through robust low-N-stress sensing and signaling, amplified protein phosphorylation and stress response, and increased photosynthesis efficiency, as well as the down-regulation of 'lavish' or redundant proteins to minimize N demand. Additionally, we screened glutathione transferase 42 (ZmGST42) and performed physiological and biochemical characterizations of the wild-type (B73) and gst42 mutant at the seedling stage. Resultantly, the wild-type exhibited stronger tolerance to low N than the mutant line. Our findings provide a better understanding of the molecular mechanisms underlying low-N tolerance during the maize grain filling stage and reveal key candidate genes for low-N-tolerance breeding in maize.

Correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations.

Background: The plasma concentrations of the four most commonly used first-line anti-tuberculosis (TB) drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and pyrazinamide (PZA), are often not within the therapeutic range. Insufficient drug exposure could lead to drug resistance and treatment failure, while excessive drug levels may lead to adverse reactions. The purpose of this study was to identify the physiological parameters influencing anti-TB drug concentrations. Methods: A retrospective cohort study was conducted. The 2-h plasma concentrations of the four drugs were measured by using the high-performance liquid chromatography-tandem mass spectrometry method. Results: A total of 317 patients were included in the study. The proportions of patients with INH, RMP, EMB, and PZA concentrations within the therapeutic range were 24.3%, 31.5%, 27.8%, and 18.6%, respectively. There were positive associations between the concentrations of INH and PZA and RMP and EMB, but negative associations were observed between the concentrations of INH and RMP, INH and EMB, RMP and PZA, and EMB and PZA. In the multivariate analysis, the influencing factors of the INH concentration were the PZA concentration, total bile acid (TBA), serum potassium, dose, direct bilirubin, prealbumin (PA), and albumin; those of the RMP concentration were PZA and EMB concentrations, weight, α-l-fucosidase (AFU), drinking, and dose; those of the EMB concentration were the RMP and PZA concentrations, creatinine, TBA and indirect bilirubin; and those of the PZA concentration were INH, RMP and EMB concentrations, sex, weight, uric acid and drinking. Conclusion: The complex correlations between the concentrations of the four first-line anti-TB drugs lead to a major challenge in dose adjustment to maintain all drugs within the therapeutic window. Levels of TBA, PA, AFU, and serum potassium should also be considered when adjusting the dose of the four drugs.

Metabolic pathways engineering for drought or/and heat tolerance in cereals.

Drought (D) and heat (H) are the two major abiotic stresses hindering cereal crop growth and productivity, either singly or in combination (D/+H), by imposing various negative impacts on plant physiological and biochemical processes. Consequently, this decreases overall cereal crop production and impacts global food availability and human nutrition. To achieve global food and nutrition security vis-a-vis global climate change, deployment of new strategies for enhancing crop D/+H stress tolerance and higher nutritive value in cereals is imperative. This depends on first gaining a mechanistic understanding of the mechanisms underlying D/+H stress response. Meanwhile, functional genomics has revealed several stress-related genes that have been successfully used in target-gene approach to generate stress-tolerant cultivars and sustain crop productivity over the past decades. However, the fast-changing climate, coupled with the complexity and multigenic nature of D/+H tolerance suggest that single-gene/trait targeting may not suffice in improving such traits. Hence, in this review-cum-perspective, we advance that targeted multiple-gene or metabolic pathway manipulation could represent the most effective approach for improving D/+H stress tolerance. First, we highlight the impact of D/+H stress on cereal crops, and the elaborate plant physiological and molecular responses. We then discuss how key primary metabolism- and secondary metabolism-related metabolic pathways, including carbon metabolism, starch metabolism, phenylpropanoid biosynthesis, γ-aminobutyric acid (GABA) biosynthesis, and phytohormone biosynthesis and signaling can be modified using modern molecular biotechnology approaches such as CRISPR-Cas9 system and synthetic biology (Synbio) to enhance D/+H tolerance in cereal crops. Understandably, several bottlenecks hinder metabolic pathway modification, including those related to feedback regulation, gene functional annotation, complex crosstalk between pathways, and metabolomics data and spatiotemporal gene expressions analyses. Nonetheless, recent advances in molecular biotechnology, genome-editing, single-cell metabolomics, and data annotation and analysis approaches, when integrated, offer unprecedented opportunities for pathway engineering for enhancing crop D/+H stress tolerance and improved yield. Especially, Synbio-based strategies will accelerate the development of climate resilient and nutrient-dense cereals, critical for achieving global food security and combating malnutrition.