Tandem Catalysts Enabling Efficient C-N Coupling toward the Electrosynthesis of Urea.

The development of a methodology for synthesizing value-added urea (CO(NH2)2) via a renewable electricity-driven C-N coupling reaction under mild conditions is highly anticipated. However, the complex catalytic active sites that act on the carbon and nitrogen species make the reaction mechanism unclear, resulting in a low efficiency of C-N coupling from the co-reduction of carbon dioxide (CO2) and nitrate (NO3-). Herein,we propose a novel tandem catalyst of Mo-PCN-222(Co), in which the Mo sites serve to facilitate nitrate reduction to the *NH2 intermediate, while the Co sites enhance CO2 reduction to carbonic oxide (CO), thus synergistically promoting C-N coupling. The synthesized Mo-PCN-222(Co) catalyst exhibited a noteworthy urea yield rate of 844.11mg h-1 g-1, alongside a corresponding Faradaic efficiency of 33.90% at -0.4 V vs. reversible hydrogen electrode (RHE). By combining in situ spectroscopic techniques with density functional theory calculations, we demonstrate that efficient C-N coupling is attributed to a tandem system in which the *NH2 and *CO intermediates produced by the Mo and Co active sites of Mo-PCN-222(Co) stabilize the formation of the *CONH2 intermediate. This study provides an effective avenue for the design and synthesis of tandem catalysts for electrocatalytic urea synthesis.

Overexpression of cry1c* Enhances Resistance against to Soybean Pod Borer (Leguminivora glycinivorella) in Soybean.

Soybean [Glycine max (L.) Merr.], an essential staple food and oil crop worldwide, boasts abundant vegetable proteins and fats beneficial for both human and animal consumption. However, the soybean pod borer (Leguminivora glycinivorella) (SPB) stands as the most destructive soybean insect pest in northeast China and other northeastern Asian regions, leading to significant annual losses in soybean yield and economic burden. Therefore, this study aims to investigate the introduction of a previously tested codon-optimized cry1c gene, cry1c*, into the soybean genome and assess its effect on the SPB infestation by generating and characterizing stable transgenic soybeans overexpressing cry1c*. The transgenic soybean lines that constitutively overexpressed cry1c* exhibited a significant reduction in the percentage of damaged seeds, reaching as low as 5% in plants under field conditions. Additionally, feeding transgenic leaves to the larvae of S. exigua, S. litura, and M. separta resulted in inhibited larval growth, decreased larval body weight, and lower survival rates compared to larvae fed on wild-type leaves. These findings showed that the transgenic lines maintained their resistance to SPB and other lepidopteran pests, especially the transgenic line KC1. Southern blotting and genome-wide resequencing analysis revealed that T-DNA integration occurred as a single copy between loci 50,868,122 and 50,868,123 of chromosome 10 in the transgenic line KC1. Therefore, the transgenic line KC1, overexpressing high levels of cry1c* in leaves and seeds, holds strong potential for commercial use in the integrated management of SPB and other lepidopteran pests.

Multicolor Photochemical Printing Inside Polymer Matrices for Advanced Photonic Anticounterfeiting.

Conventional security inks, generally directly printed on the data page surface, are vulnerable to counterfeiters, thereby raising the risk of chemical structural deciphering. In fact, polymer film-based data pages with customized patterns embedded within polymer matrix, rather than printed on the surface, emerge as a promising solution. Therefore, the key lies in developing fluorophores offering light dose-controlled fluorescent color inside polymer matrices. Though conventional fluorophores often suffer from photobleaching and uncontrolled photoreactions, disqualifying them for this purpose. Herein a diphenanthridinylfumaronitrile-based phototransformers (trans-D5) that undergoes photoisomerization and subsequent photocyclization during photopolymerization of the precursor, successively producing cis- and cyclo-D5 with stepwise redshifted solid-state emissions is developed. The resulting cyclo-D5 exhibits up to 172 nm emission redshift in rigidifying polymer matrices, while trans-D5 experiences a slightly blueshifted emission (≈28 nm), cis-D5 undergoes a modest redshift (≈14 nm). The markedly different rigidochromic behaviors of three D5 molecules within polymer matrices enable multicolor photochemical printing with a broad hue ranging from 38 to 10 via an anticlockwise direction in Munsell color space, yielding indecipherable fluorescent patterns in polymer films. This work provides a new method for document protection and implements advanced security features that are unattainable with conventional inks.

Multibarrier-penetrating drug delivery systems for deep tumor therapy based on synergistic penetration strategy.

Nanotherapies, valued for their high efficacy and low toxicity, frequently serve as antitumor treatments, but do not readily penetrate deep into tumor tissues and cells. Here we developed an improved tumor-penetrating peptide (TPP)-based drug delivery system. Briefly, the established TPP iNGR was modified to generate a linear NGR peptide capable of transporting nanotherapeutic drugs into tumors through a CendR pathway-dependent, neuropilin-1 receptor-mediated process. Although TPPs have been reported to reach intended tumor targets, they often fail to penetrate cell membranes to deliver tumoricidal drugs to intracellular targets. We addressed this issue by harnessing cell penetrating peptide technology to develop a liposome-based multibarrier-penetrating delivery system (mbPDS) with improved synergistic drug penetration into deep tumor tissues and cells. The system incorporated doxorubicin-loaded liposomes coated with nona-arginine (R9) CPP and cyclic iNGR (CRNGRGPDC) molecules, yielding Lip-mbPDS. Lip-mbPDS tumor-targeting, tumor cell/tissue-penetrating and antitumor capabilities were assessed using CD13-positive human fibrosarcoma-derived cell (HT1080)-based in vitro and in vivo tumor models. Lip-mbPDS evaluation included three-dimensional layer-by-layer confocal laser scanning microscopy, cell internalization/toxicity assays, three-dimensional tumor spheroid-based penetration assays and antitumor efficacy assays conducted in an animal model. Lip-mbPDS provided enhanced synergistic drug penetration of multiple biointerfaces for potentially deep tumor therapeutic outcomes.

Inhibition of EHMT1/2 rescues synaptic damage and motor impairment in a PD mouse model.

Epigenetic dysregulation that leads to alterations in gene expression and is suggested to be one of the key pathophysiological factors of Parkinson's disease (PD). Here, we found that α-synuclein preformed fibrils (PFFs) induced histone H3 dimethylation at lysine 9 (H3K9me2) and increased the euchromatic histone methyltransferases EHMT1 and EHMT2, which were accompanied by neuronal synaptic damage, including loss of synapses and diminished expression levels of synaptic-related proteins. Furthermore, the levels of H3K9me2 at promoters in genes that encode the synaptic-related proteins SNAP25, PSD95, Synapsin 1 and vGLUT1 were increased in primary neurons after PFF treatment, which suggests a linkage between H3K9 dimethylation and synaptic dysfunction. Inhibition of EHMT1/2 with the specific inhibitor A-366 or shRNA suppressed histone methylation and alleviated synaptic damage in primary neurons that were treated with PFFs. In addition, the synaptic damage and motor impairment in mice that were injected with PFFs were repressed by treatment with the EHMT1/2 inhibitor A-366. Thus, our findings reveal the role of histone H3 modification by EHMT1/2 in synaptic damage and motor impairment in a PFF animal model, suggesting the involvement of epigenetic dysregulation in PD pathogenesis.

Development of Fluorescence-Based Assays for Key Viral Proteins in the SARS-CoV-2 Infection Process and Lifecycle.

Since the appearance of SARS-CoV-2 in 2019, the ensuing COVID-19 (Corona Virus Disease 2019) pandemic has posed a significant threat to the global public health system, human health, life, and economic well-being. Researchers worldwide have devoted considerable efforts to curb its spread and development. The latest studies have identified five viral proteins, spike protein (Spike), viral main protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), and viral helicase (Helicase), which play crucial roles in the invasion of SARS-CoV-2 into the human body and its lifecycle. The development of novel anti-SARS-CoV-2 drugs targeting these five viral proteins holds immense promise. Therefore, the development of efficient, high-throughput screening methodologies specifically designed for these viral proteins is of utmost importance. Currently, a plethora of screening techniques exists, with fluorescence-based assays emerging as predominant contenders. In this review, we elucidate the foundational principles and methodologies underpinning fluorescence-based screening approaches directed at these pivotal viral targets, hoping to guide researchers in the judicious selection and refinement of screening strategies, thereby facilitating the discovery and development of lead compounds for anti-SARS-CoV-2 pharmaceuticals.

Fast-Swimming Soft Robotic Fish Actuated by Bionic Muscle.

Soft underwater swimming robots actuated by smart materials have unique advantages in exploring the ocean, such as low noise, high flexibility, and friendly environment interaction ability. However, most of them typically exhibit limited swimming speed and flexibility due to the inherent characteristics of soft actuation materials. The actuation method and structural design of soft robots are key elements to improve their motion performance. Inspired by the muscle actuation and swimming mechanism of natural fish, a fast-swimming soft robotic fish actuated by a bionic muscle actuator made of dielectric elastomer is presented. The results show that by controlling the two independent actuating units of a biomimetic actuator, the robotic fish can not only achieve continuous C-shaped body motion similar to natural fish but also have a large bending angle (maximum unidirectional angle is about 40°) and thrust force (peak thrust is about 14 mN). In addition, the coupling relationship between the swimming speed and actuating parameters of the robotic fish is established through experiments and theoretical analysis. By optimizing the control strategy, the robotic fish can demonstrate a fast swimming speed of 76 mm/s (0.76 body length/s), which is much faster than most of the reported soft robotic fish driven by nonbiological soft materials that swim in body and/or caudal fin propulsion mode. What's more, by applying programmed voltage excitation to the actuating units of the bionic muscle, the robotic fish can be steered along specific trajectories, such as continuous turning motions and an S-shaped routine. This study is beneficial for promoting the design and development of high-performance soft underwater robots, and the adopted biomimetic mechanisms, as well as actuating methods, can be extended to other various flexible devices and soft robots.

Steering Muscle-Based Bio-Syncretic Robot Through Bionic Optimized Biped Mechanical Design.

Bio-syncretic robots consisting of artificial structures and living muscle cells have attracted much attention owing to their potential advantages, such as high drive efficiency, miniaturization, and compatibility. Motion controllability, as an important factor related to the main performance of bio-syncretic robots, has been explored in numerous studies. However, most of the existing bio-syncretic robots still face challenges related to the further development of steerable kinematic dexterity. In this study, a bionic optimized biped fully soft bio-syncretic robot actuated by two muscle tissues and steered with a direction-controllable electric field generated by external circularly distributed multiple electrodes has been developed. The developed bio-syncretic robot could realize wirelessly steerable motion and effective transportation of microparticle cargo on artificial polystyrene and biological pork tripe surfaces. This study may provide an effective strategy for the development of bio-syncretic robots and other related studies, such as nonliving soft robot design and muscle tissue engineering.

Design, Synthesis, Nematicidal, and Fungicidal Activities of Novel Azo and Azoxy Compounds.

Bursaphelenchus xylophilus (B. xylophilus) and Meloidogyne are parasitic nematodes that have caused severe ecological and economic damage in pinewood and crops, respectively. Jietacins (jietacin A and B) were found to have excellent biological activity against B. xylophilus. Based on our tremendous demand for chemicals against B. xylophilus, a novel scaffold based on the azo and azoxy groups was designed, and a series of compounds were synthesized. In the bioassay, Ia, IIa, IIc, IId, and IVa exhibited higher activity against B. xylophilus in vitro than avermectin (LC50 = 2.43 µg·mL-1) with LC50 values of 1.37, 1.12, 0.889, 1.56, and 1.10 µg·mL-1, respectively. Meanwhile, Ib, Ic, IIc, and IVa showed good inhibition effects against Meloidogyne in vivo at the concentrations of 80 and 40 µg·mL-1 with inhibition rates of 89.0% and 81.6%, 95.6% and 75.7%, 96.3% and 41.2%, and 86.8% and 78.7%, respectively. In fungicidal activity in vitro, IIb and IVa exhibited excellent effect against Botryosphaeria dothidea with the inhibition of 82.59% and 85.32% at the concentration of 10 µg·mL-1, while the inhibition of Ia was 83.16% against Rhizoctonia solani at the concentration of 12.5 µg·mL-1. Referring to the biological activity against B. xylophilus, a 3D-QASR model was built in which the electron-donating group and small group at the 4-phenylhydrazine were favorable for the activity. In general, the novel azoxy compounds, especially IIc possess great potential for application in the prevention of B. xylophilus.

STK11 (LKB1) mutation suppresses ferroptosis in lung adenocarcinoma by facilitating monounsaturated fatty acid synthesis.

Serine/threonine kinase 11 (STK11), a tumor suppressor gene, exhibits frequent mutations in lung adenocarcinoma (LUAD). However, the specific molecular mechanisms by which STK11 mutations exert an influence on the biosynthesis of monounsaturated fatty acids (MUFAs) and subsequently affect ferroptosis in LUAD remain indistinct. In this study, bioinformatic analysis was employed to probe into the linkage between STK11 and key inhibitory genes of ferroptosis, namely SLC7A11 and SCD1, in LUAD tissues. Quantitative reverse transcription polymerase chain reaction was employed to assess the expression of STK11 in both wild-type and mutant STK11 LUAD cells, cell counting kit-8 to assess cell viability, and flow cytometry to detect apoptosis. A transmission electron microscope was utilized to observe mitochondrial morphology, and Western blot to ascertain the protein expression of STK11, ferroptosis-related proteins, and the enzyme SCD1 involved in MUFA synthesis. Oil red O staining was employed to test the distribution of lipid droplets in cancer cells, and a lipid quantification method to measure the content of MUFAs. Commercial kits were employed to assess the levels of lipid reactive oxygen species, malondialdehyde, glutathione, and Fe2+ in cells. The result revealed a negative correlation between STK11 and SLC7A11 as well as SCD1, with STK11 expression downregulated in mutant STK11 LUAD cells. Furthermore, STK11 mutations were found to suppress ferroptosis in LUAD cells by affecting MUFA synthesis. Subsequent rescue assays demonstrated that STK11 mutations hindered ferroptosis by impacting the synthesis of MUFAs in LUAD cells. This study provided evidence that STK11 mutations suppressed ferroptosis in LUAD cells by promoting MUFA synthesis, thus offering a novel research direction in the management of LUAD.

Accidental ingestion of multiple magnetic beads by children and their impact on the gastrointestinal tract: a single-center study.

OBJECTIVE: In this study, we aimed to enhance the treatment protocols and help understand the harm caused by the accidental ingestion of magnetic beads by children. METHODS: Data were collected from 72 children with multiple gastrointestinal perforations or gastrointestinal obstructions. The 72 pediatric patients were divided into a perforation and a non-perforation group. The data collected for the analysis included the gender, age, medical history, place of residence (rural or urban), and symptoms along with the educational background of the caregiver, the location and quantity of any foreign bodies discovered during the procedure, whether perforation was confirmed during the procedure, and the number of times magnetic beads had been accidentally ingested. RESULTS: The accuracy rate of preoperative gastrointestinal perforation diagnosis via ultrasound was 71%, while that of the upright abdominal X-ray method was only 46%. In terms of symptoms, the risk of perforation was 13.844 and 12.703 times greater in pediatric patients who experienced vomiting and abdominal pain with vomiting and abdominal distension, respectively, compared to patients in an asymptomatic state. There were no statistical differences between the perforation and the non-perforation groups in terms of age, gender, medical history, and the number of magnetic beads ingested (P > 0.05); however, there were statistical differences in terms of white blood cell count (P = 0.048) and c-reactive protein levels (P = 0.033). A total of 56% of cases underwent a laparotomy along with perforation repair and 19% underwent gastroscopy along with laparotomy. All pediatric patients recovered without complications following surgery. CONCLUSION: Abdominal ultrasonography and/or upright abdominal X-ray analyses should be carried out as soon as possible in case of suspicion of accidental ingestion of magnetic beads by children. In most cases, immediate surgical intervention is required. Given the serious consequences of ingesting this type of foreign body, it is essential to inform parents and/or caregivers about the importance of preventing young children from using such products.

Mn4+/Eu3+ co-doped fluoride toward a blue light-excited optical fiber thermometer.

The ongoing development of ratiometric optical thermometry is mainly trapped in thermally coupled levels of rare-earth ions and inefficient ultraviolet excitation. Herein, a new-type multiple sharp line emitting, blue light-excited K2NaInF6:Mn4+, Eu3+ fluoride phosphor has been reported as a ratiometric thermometer. The f-f transition of Eu3+ paves a steady reference to a highly temperature sensitive Mn4+d-d transition and enables high relative sensitivity of 1.65% K-1 at 573 K. An optical fiber thermometry on a household oven with a relative standard deviation of 0.11% surpasses the standard of precision measurement, showing great potential in practical application. This discovery offers a highly sensitive neotype blue light-excitable ratiometric temperature sensor, that is Mn4+-doped fluoride, promoting practical applications of optical thermometry.

Strain-restricted transfer of ferromagnetic electrodes for constructing reproducibly superior-quality spintronic devices.

Spintronic device is the fundamental platform for spin-related academic and practical studies. However, conventional techniques with energetic deposition or boorish transfer of ferromagnetic metal inevitably introduce uncontrollable damage and undesired contamination in various spin-transport-channel materials, leading to partially attenuated and widely distributed spintronic device performances. These issues will eventually confuse the conclusions of academic studies and limit the practical applications of spintronics. Here we propose a polymer-assistant strain-restricted transfer technique that allows perfectly transferring the pre-patterned ferromagnetic electrodes onto channel materials without any damage and change on the properties of magnetism, interface, and channel. This technique is found productive for pursuing superior-quality spintronic devices with high controllability and reproducibility. It can also apply to various-kind (organic, inorganic, organic-inorganic hybrid, or carbon-based) and diverse-morphology (smooth, rough, even discontinuous) channel materials. This technique can be very useful for reliable device construction and will facilitate the technological transition of spintronic study.

Improving regional medical laboratory center report quality through a report recall management system.

OBJECTIVES: Currently, most medical laboratories do not have a dedicated software for managing report recalls, and relying on traditional manual methods or laboratory information system (LIS) to record recall data is no longer sufficient to meet the quality management requirements in the large regional laboratory center. The purpose of this article was to describe the research process and preliminary evaluation results of integrating the Medical Laboratory Electronic Record System (electronic record system) laboratory report recall function into the iLab intelligent management system for quality indicators (iLab system), and to introduce the workflow and methods of laboratory report recall management in our laboratory. METHODS: This study employed cluster analysis to extract commonly used recall reasons from laboratory report recall records in the electronic record system. The identified recall reasons were validated for their applicability through a survey questionnaire and then incorporated into the LIS for selecting recall reasons during report recall. The statistical functionality of the iLab system was utilized to investigate the proportion of reports using the selected recall reasons among the total number of reports, and to perform visual analysis of the recall data. Additionally, we employed P-Chart to establish quality targets and developed a "continuous improvement process" electronic flow form. RESULTS: The reasons for the recall of laboratory reports recorded in the electronic recording system were analyzed. After considering the opinions of medical laboratory personnel, a total of 12 recall reasons were identified, covering 73.05 % (1854/2538) of the recalled laboratory reports. After removing data of mass spectra lab with significant anomalies, the coverage rate increased to 82.66 % (1849/2237). The iLab system can generate six types of statistical graphs based on user needs, including statistical time, specialty labs (or divisions), test items, reviewers, reasons for report recalls, and distribution of the recall frequency of 0-24 h reports. The control upper limit of the recall rate of P-Chart based on laboratory reports can provide quality targets suitable for each professional group at the current stage. Setting the five stages of continuous process improvement reasonably and rigorously can effectively achieve the goal of quality enhancement. CONCLUSIONS: The enhanced iLab system enhances the intelligence and sustainable improvement capability of the recall management of laboratory reports, thus improving the efficiency of the recall management process and reducing the workload of laboratory personnel.

Effect of public square dancing combined with serotonin reuptake inhibitors on persistent postural-perceptual dizziness (PPPD) in middle-aged and older women.

BACKGROUND: Persistent postural-perceptual dizziness (PPPD) is a functional vestibular disorder that causes chronic dizziness and limits daily activities. Although pharmacology, vestibular rehabilitation, and cognitive behavioral therapy have been proposed to have some efficacy, they have certain limitations. Some patients with PPPD report that public square dancing can effectively relieve the symptoms of dizziness and instability, and their mood improves. OBJECTIVE: To evaluate the effects of combining public square dancing with serotonin reuptake inhibitors (SSRIs/SNRIs) on the subjective sensations of dizziness, balance enhancement, anxiety, and depressive symptom regulation in middle-aged and older women with PPPD. MATERIALS AND METHODS: In this trial, 124 patients diagnosed with PPPD were enrolled. Among them, 64 patients were randomly assigned to the experimental group (EG), where they received square dance training combined with serotonin reuptake inhibitors. The remaining 60 cases were randomly assigned to the control group (CG), where they received only serotonin reuptake inhibitors and did not participate in organized sports activities, allowing them freedom in their daily lives. Data from the Dizziness Handicap Inventory (DHI), Hospital Anxiety and Depression Scale (HADS), Active-specific Balance Confidence Scale (ABC), and Vestibular Disorder Activities of Daily Living Scale (VADL) were collected and compared at the beginning, 3 months, and 6 months of the trial to evaluate the effect of public square dancing on middle-aged and older women with PPPD. RESULTS: There were no significant differences between the EG and CG before the trial. Compared with baseline measures, DHI, HADS, ABC, and VADL scores improved as the experiment progressed, and the improvements were more pronounced in the EG. CONCLUSION: Public square dancing combined with serotonin reuptake inhibitors has a positive impact on the subjective sensations of dizziness, balance enhancement, anxiety, and depressive symptom regulation in middle-aged and older women with PPPD.

Fine-tuning bromide AIE probes for Hg2+ detection in mitochondria with wash-free staining.

Mercury ions (Hg2+) primarily target mitochondria in the cells. Therefore, the development of novel probes that specifically target mitochondria in the presence of Hg2+ is of immense importance. Most previously reported probes that utilize the softness of S, Te, O, and/or N atoms for Hg2+ binding often face problems such as fluorescence quenching and off-target signals. In this study, bromide-hydrocarbon pyridinium salts were designed to target the mitochondria and chelate Hg2+ via Hg-Br coordination bonds. As a prototype, four aggregation-induced emission (AIE) fluorogens, namely TPP-Br, TPP-Cl, R1, and R2, with a similar D-π-A structure but slight differences in their halogen substituents, were designed. Among them, only TPP-Br achieved the highly selective and sensitive detection of Hg2+ by triggering its AIE properties, resulting in remarkable emission enhancement (80-fold), colorimetry, and the Tyndall effect. TPP-Br exhibited high selectivity and sensitivity to Hg2+ with a detection limit of 0.35 µM, rapid response time (<10 s), and large Stokes shift of 185 nm. Their interaction modes were studied using a combination of 1H nuclear magnetic resonance spectroscopy, scanning electron microscopy, fluorescent lifetime decay, and theoretical calculations. TPP-Br exhibited a low emission background in cells, whereas in the presence of Hg2+, mitochondria were lit up with wash-free staining. This study provides a powerful tool for accurately diagnosing mercury poisoning-related diseases in mitochondria.

Antitumor Effect of Poplar Propolis on Human Cutaneous Squamous Cell Carcinoma A431 Cells.

Propolis is a gelatinous substance processed by western worker bees from the resin of plant buds and mixed with the secretions of the maxillary glands and beeswax. Propolis has extensive biological activities and antitumor effects. There have been few reports about the antitumor effect of propolis against human cutaneous squamous cell carcinoma (CSCC) A431 cells and its potential mechanism. CCK-8 assays, label-free proteomics, RT-PCR, and a xenograft tumor model were employed to explore this possibility. The results showed that the inhibition rate of A431 cell proliferation by the ethanol extract of propolis (EEP) was dose-dependent, with an IC50 of 39.17 µg/mL. There were 193 differentially expressed proteins in the EEP group compared with the control group (p < 0.05), of which 103 proteins (53.37%) were upregulated, and 90 proteins (46.63%) were downregulated. The main three activated and suppressed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were extracellular matrix (ECM)-receptor interaction, amoebiasis, cell adhesion molecules (CAMs), nonalcoholic fatty liver disease (NAFLD), retrograde endocannabinoid signaling, and Alzheimer's disease. The tumor volume of the 100 mg/kg EEP group was significantly different from that of the control group (p < 0.05). These results provide a theoretical basis for the potential treatment of human CSCC A431 cell tumors using propolis.

Gene editing of ZmGA20ox3 improves plant architecture and drought tolerance in maize.

KEY MESSAGE: Editing ZmGA20ox3 can achieve the effect similar to applying Cycocel, which can reduce maize plant height and enhance stress resistance. Drought stress, a major plant abiotic stress, is capable of suppressing crop yield performance severely. However, the trade-off between crop drought tolerance and yield performance turns out to be significantly challenging in drought-resistant crop breeding. Several phytohormones [e.g., gibberellin (GA)] have been reported to play a certain role in plant drought response, which also take on critical significance in plant growth and development. In this study, the loss-of-function mutations of GA biosynthesis enzyme ZmGA20ox3 were produced using the CRISPR-Cas9 system in maize. As indicated by the result of 2-year field trials, the above-mentioned mutants displayed semi-dwarfing phenotype with the decrease of GA1, and almost no yield loss was generated compared with wild-type (WT) plants. Interestingly, as revealed by the transcriptome analysis, differential expressed genes (DEGs) were notably enriched in abiotic stress progresses, and biochemical tests indicated the significantly increased ABA, JA, and DIMBOA levels in mutants, suggesting that ZmGA20ox3 may take on vital significance in stress response in maize. The in-depth analysis suggested that the loss function of ZmGA20ox3 can enhance drought tolerance in maize seedling, reduce Anthesis-Silking Interval (ASI) delay while decreasing the yield loss significantly in the field under drought conditions. The results of this study supported that regulating ZmGA20ox3 can improve plant height while enhancing drought resistance in maize, thus serving as a novel method for drought-resistant genetic improvement in maize.

Intramuscularly injected long-acting testosterone-cholesterol prodrug suspension with three different particle sizes: extended in vitro release and enhanced in vivo safety.

The testosterone undecanoate oil solution is the most widely used injection of testosterone for long-acting effects on the market, whereas the formulation carries the potential risk of causing pulmonary vascular embolism, inflammation, and pain at the injection site. Therefore, a sustained-released long-acting injection of testosterone with strong security is urgently exploited. Herein, a poorly water-soluble testosterone-cholesterol prodrug (TST-Chol) was synthesized by esterification. The water solubility of TST-Chol was decreased by 644 folds in comparison to that of testosterone (TST). Moreover, suspensions of TST and TST-Chol were prepared and analyzed in vitro, utilizing three distinct particle sizes: small-sized nanocrystals (SNCs) measuring 300 nm, medium-sized microcrystals (MMCs) measuring 12 µm, and large-sized microcrystals (LMCs) measuring 20 µm. The findings from the in vitro release study indicated that the sustained release of the drug was significantly influenced by the solubility and particle sizes of the suspension. Notably, the suspensions with low water solubility and larger particle sizes exhibited a more desirable sustained-release effect in vitro. Furthermore, the study on pharmacokinetics exhibited that TST-Chol SNCs produced a sustained TST plasma concentration in vivo for up to 40 days and no obvious pathological changes in lung tissue were found. Our study indicated that solubility and particle sizes of suspensions had made a difference in pharmacokinetics and provided a valuable reference for the advancement of long-acting injections.

Meta-Analysis of the Efficacy of Levosimendan in the Treatment of Severe Sepsis Complicated with Septic Cardiomyopathy.

INTRODUCTION: Sepsis is a medical condition characterized by acute organ dysfunction and uncontrolled inflammation. Organ dysfunction in sepsis is the primary cause of mortality in patients with myocardial dysfunction. Levosimendan is a vasodilating and inotropic agent used in patients with acute heart failure and has resulted in decreased morbidity and mortality in these patients. Our main objective is to examine levosimendan's efficacy in treating severe sepsis complicated with septic cardiomyopathy. METHODS: We systematically searched five databases, PubMed, Web of Science, Embase, Cochrane Library and BioMed Central, for articles and publications from their inception to 2023. Our study adopted the PICOS approach in identifying suitable publications during the systematic search. Inclusion criteria included randomized, controlled trials utilizing levosimendan in adult patients diagnosed with septic shock or severe sepsis. We excluded non-English publications and non-randomized controlled trials. The Newcastle-Ottawa scale (NOS) scale was used to assess the methodological quality, while the risk of bias was assessed through the Cochrane Risk of bias tool. All statistical analyses were performed using RevMan version 5.4. RESULTS: Eight studies met the eligibility criteria and were included in the analysis. There was a statistically significant positive effect on cardiac input in patients treated with levosimendan compared to those treated with dobutamine (p < 0.001). Similarly, there were positive effects on left ventricular ejection fraction (LVEF) (p < 0.001) and left ventricular stroke work index (LVSWI) (p < 0.001). We observed a significant reduction in mortality (p < 0.01) and serum levels of lactic acid (p < 0.01). DISCUSSION: Levosimendan is a calcium sensitizer associated with an influx of calcium ions and activation of ATP-dependent potassium channels that increases myocardial contractility contractions, enhances vasodilation and improves oxygen supply to the cells and tissues. CONCLUSION: Levosimendan is highly efficacious and safe in the management of sepsis and sepsis-induced cardiomyopathy.