Efficacy and safety of empagliflozin in combination with insulin in Chinese patients with type 2 diabetes and insufficient glycaemic control: A phase III, randomized, double-blind, placebo-controlled, parallel study.

AIM: To evaluate the efficacy and safety of empagliflozin in combination with insulin ± oral antidiabetic drugs (OADs) over 24 weeks, in Chinese patients with type 2 diabetes (T2D) who had insufficient glycaemic control. MATERIALS AND METHODS: This was a randomized, double-blind, placebo-controlled, parallel group, multicentre phase III study. Adult patients with T2D and insufficient glycaemic control who received insulin ± up to two OADs were randomized (1:1:1) to receive empagliflozin 10 or 25 mg, or placebo for 24 weeks. The primary endpoint was change from baseline in HbA1c at week 24. RESULTS: Of 219 randomized patients, 73 patients were in each treatment group; baseline characteristics were comparable among the groups. There was a significantly larger decrease from baseline in HbA1c (adjusted mean treatment difference -0.99 and -0.98 for in the empagliflozin 10 and 25 mg groups, respectively; P < .0001) with both doses of empagliflozin than with placebo. There were also significantly larger decreases from baseline in fasting plasma glucose, 2-hour postprandial glucose and body weight with both empagliflozin doses than with placebo. Among patients in the empagliflozin 10 mg, 25 mg and placebo groups, 17.8%, 9.6% and 11.0% reported confirmed hypoglycaemic events, respectively (nominal P = .2422 and .7661 in the empagliflozin 10 and 25 mg groups, respectively), and no Clinical Events Committee-confirmed diabetic ketoacidosis events were reported. CONCLUSIONS: In Chinese patients with T2D, empagliflozin combined with insulin ± OADs improved glycaemic control and was well tolerated, without an increased risk of hypoglycaemia.

Polymyxin B therapy based on therapeutic drug monitoring in carbapenem-resistant organisms sepsis: the PMB-CROS randomized clinical trial.

BACKGROUND: The appropriate administration regimen of polymyxin B is yet controversial. The present study aimed to explore the optimal dose of polymyxin B under therapeutic drug monitoring (TDM) guidance. METHODS: In China's Henan province, 26 hospitals participated in a randomized controlled trial. We included patients with sepsis caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) susceptible to polymyxin B. The patients were randomly divided into a high-dose (HD) group or a low-dose (LD) group and received 150 mg loading dose, 75 mg every 12 h and 100 mg loading dose, 50 mg every 12 h, respectively. TDM was employed to determine if the dose of polymyxin B needs adjustment based on the area under the concentration-time curve across 24 h at a steady state (ssAUC0-24) of 50-100 mg h/L. The primary outcome was the 14-day clinical response, and the secondary outcomes included 28- and 14-day mortality. RESULTS: This trial included 311 patients, with 152 assigned to the HD group and 159 assigned to the LD group. Intention-to-treat analysis showed that the 14-day clinical response was non-significant (p = 0.527): 95/152 (62.5%) in the HD group and 95/159 (59.7%) in the LD group. Kaplan-Meier's 180-day survival curve showed survival advantage in the HD group than in the LD group (p = 0.037). More patients achieved the target ssAUC0-24 in the HD than in the LD group (63.8% vs. 38.9%; p = 0.005) and in the septic shock subgroup compared to all subjects (HD group: 71.4% vs. 63.8%, p = 0.037; LD group: 58.3% vs. 38.9%, p = 0.0005). Also, the target AUC compliance was not correlated with clinical outcomes but with acute kidney injury (AKI) (p = 0.019). Adverse events did not differ between the HD and LD groups. CONCLUSION: A fixed polymyxin B loading dose of 150 mg and a maintenance dose of 75 mg every 12 h was safe for patients with sepsis caused by CR-GNB and improves long-term survival. The increased AUC was associated with increased incidence of AKI, and TDM results were valued to prevent AKI. Trial registration Trial registration ClinicalTrials.gov: ChiCTR2100043208, Registration date: January 26, 2021.

The influence of high-speed train's transient pressure change on the fetal growth of SD rats.

This research aims to explore the influence of transient pressure fluctuation inside high-speed trains passing throught tunnels on the fetal growth of Sprague - Dawley (SD) rats. A pressure variation simulation system was designed and exposure experiments were performed on SD rats. Forty-eight SD rats are divided into two control groups and two experimental groups, and are then exposed to transient pressure alternation (-1200 Pa ~1200 Pa) from gestation day 0 to gestation day 5 (GD 0-5). Fetal growth and development indicators on GD12 and GD18 between experimental and control groups were compared. Statistical results showed that, compared to the control group, the key indicators in the experimental group, including placental weight, placental diameter, fetal weight, and crown-to-rump length have decreased by 4.77%, 3.38%, 6.20%, and 3.75% respectively on GD18. The findings imply that the pressure fluctuation environment of high-speed trains has potential effects on the fetal growth of SD rats.

Simultaneous Targeted Analysis of GGT and Its H-Type mRNA in HepG2 Cells Based on Degradable Silicon Nanomaterials.

Most important physiological processes in live cells are usually maintained by the interaction of multiple related biomolecules; the multi-target simultaneous analysis of these related molecules can better reflect the dynamic changes of their biological regulatory processes, providing more comprehensive information for diseases diagnosis and research. Herein, we have constructed the degradable multifunctional silica nanomaterials from the prepared degradable organic silicon source and further established degradable composite nanoprobes (DCNPs). The low toxicity of DCNPs could reduce the impact on normal physiological processes in cells and achieve the needs of living cell analysis applications; by the loading of the gamma-glutamyltransferase (GGT) activity-identification probe (Cy-GGT) and surface nucleic acid-recognizing molecular beacon (hairpin) modification, the DCNP realized the simultaneous image analysis of GGT and its related H-type mutated GGT mRNA (H-mRNA) in HepG2 cells and their quantitative detection in vitro. Compared with the traditional multi-target analysis strategy, the lack of targets' physiological mechanism connection was improved, and the combined application of small molecular probes and nucleic acid analysis structures was realized under the control of the cross-influence. This strategy is expected to provide a new direction for the design of multi-target analysis in live cells and provide more accurate analytical tools for clinical research and cancer therapy.

Peripheral perfusion index predicting prolonged ICU stay earlier and better than lactate in surgical patients: an observational study.

BACKGROUND: Peripheral perfusion index (PPI) is an indicator reflecting perfusion. Patients undergoing long time surgeries are more prone to hypoperfusion and increased lactate. Few studies focusing on investigating the association between PPI and surgical patients' prognoses. We performed this study to find it out. METHODS: From January 2019 to September 2019, we retrospected all surgical patients who were transferred to ICU, Xinyang Central hospital, Henan province, China. Inclusive criteria: age ≥ 18 years old; surgical length ≥ 120 min. Exclusive criteria: died in ICU; discharging against medical advice; existing diseases affecting blood flow of upper limbs, for example, vascular thrombus in arms; severe liver dysfunction. We defined "prolonged ICU stay" as patients with their length of ICU stay longer than 48 h. According to the definition, patients were divided into two groups: "prolonged group" (PG) and "non-prolong group" (nPG). Baseline characteristics, surgical and therapeutic information, ICU LOS, SOFA and APACHE II were collected. Besides we gathered data of following parameters at 3 time points (T0: ICU admission; T1: 6 h after admission; T2: 12 h after admission): mean artery pressure (MAP), lactate, heart rate (HR), PPI and body temperature. Data were compared between the 2 groups. Multivariable binary logistic regression and ROC (receiver operating characteristic) curves were performed to find the association between perfusion indictors and ICU LOS. RESULTS: Eventually, 168 patients were included, 65 in PG and 103 in nPG. Compared to nPG, patients in PG had higher blood lactate and lower PPI. PPI showed significant difference between two groups earlier than lactate (T0 vs T1). The value of PPI at two time points was lower in PG than nPG(T0: 1.09 ± 0.33 vs 1.41 ± 0.45, p = 0.001; T1: 1.08 ± 0.37 vs 1.49 ± 0.41, p < 0.001). Increased lactateT1(OR 3.216; 95% CI 1.253-8.254, P = 0.015) and decreased PPIT1 (OR 0.070; 95% CI 0.016-0.307, P < 0.001) were independently associated with prolonged ICU stay. The area under ROC of the PPIT1 for predicting ICU stay> 48 h was 0.772, and the cutoff value for PPIT1 was 1.35, with 83.3% sensitivity and 73.8% specificity. CONCLUSIONS: PPI and blood lactate at T1(6 h after ICU admission) are associated with ICU LOS in surgical patient. Compared to lactate, PPI indicates hypoperfusion earlier and more accurate in predicting prolonged ICU stay.

[Analysis and Processing of Flow Alarm about Fresenius 4008 S Hemodialysis Machine].

The Fresenius 4008 S hemodialysis machine is one of the main hemodialysis machines in our hospital. Because of its longer service life, the probability of malfunction is larger. For flow alarm is the typical fault of this model, we combined with practical maintenance experience and theoretical technology, then briefly analyzed and summarized the malfunction. On the principle of easy to difficult, we check in order from five aspects, they are pipeline blockage, aging of the degassing pump or flow pump, the float switch malfunction, valve abnormality and the control circuit problem. Through this one-by-one and systematic troubleshooting, the flow alarm can usually be solved, also we can save the maintenance time and the cost.

Aluminum Toxicity-Induced Alterations of Leaf Proteome in Two Citrus Species Differing in Aluminum Tolerance.

Seedlings of aluminum-tolerant 'Xuegan' (Citrus sinensis) and Al-intolerant 'sour pummelo' (Citrus grandis) were fertigated for 18 weeks with nutrient solution containing 0 and 1.2 mM AlCl3·6H2O. Al toxicity-induced inhibition of photosynthesis and the decrease of total soluble protein only occurred in C. grandis leaves, demonstrating that C. sinensis had higher Al tolerance than C. grandis. Using isobaric tags for relative and absolute quantification (iTRAQ), we obtained more Al toxicity-responsive proteins from C. sinensis than from C. grandis leaves, which might be responsible for the higher Al tolerance of C. sinensis. The following aspects might contribute to the Al tolerance of C. sinensis: (a) better maintenance of photosynthesis and energy balance via inducing photosynthesis and energy-related proteins; (b) less increased requirement for the detoxification of reactive oxygen species and other toxic compounds, such as aldehydes, and great improvement of the total ability of detoxification; and (c) upregulation of low-phosphorus-responsive proteins. Al toxicity-responsive proteins related to RNA regulation, protein metabolism, cellular transport and signal transduction might also play key roles in the higher Al tolerance of C. sinensis. We present the global picture of Al toxicity-induced alterations of protein profiles in citrus leaves, and identify some new Al toxicity-responsive proteins related to various biological processes. Our results provide some novel clues about plant Al tolerance.

Root iTRAQ protein profile analysis of two Citrus species differing in aluminum-tolerance in response to long-term aluminum-toxicity.

BACKGROUND: Limited information is available on aluminum (Al)-toxicity-responsive proteins in woody plant roots. Seedlings of 'Xuegan' (Citrus sinensis) and 'Sour pummelo' (Citrus grandis) were treated for 18 weeks with nutrient solution containing 0 (control) or 1.2 mM AlCl3 · 6H2O (+Al). Thereafter, we investigated Citrus root protein profiles using isobaric tags for relative and absolute quantification (iTRAQ). The aims of this work were to determine the molecular mechanisms of plants to deal with Al-toxicity and to identify differentially expressed proteins involved in Al-tolerance. RESULTS: C. sinensis was more tolerant to Al-toxicity than C. grandis. We isolated 347 differentially expressed proteins from + Al Citrus roots. Among these proteins, 202 (96) proteins only presented in C. sinensis (C. grandis), and 49 proteins were shared by the two species. Of the 49 overlapping proteins, 45 proteins were regulated in the same direction upon Al exposure in the both species. These proteins were classified into following categories: sulfur metabolism, stress and defense response, carbohydrate and energy metabolism, nucleic acid metabolism, protein metabolism, cell transport, biological regulation and signal transduction, cell wall and cytoskeleton metabolism, and jasmonic acid (JA) biosynthesis. The higher Al-tolerance of C. sinensis may be related to several factors, including: (a) activation of sulfur metabolism; (b) greatly improving the total ability of antioxidation and detoxification; (c) up-regulation of carbohydrate and energy metabolism; (d) enhancing cell transport; (e) decreased (increased) abundances of proteins involved in protein synthesis (proteiolysis); (f) keeping a better balance between protein phosphorylation and dephosphorylation; and (g) increasing JA biosynthesis. CONCLUSIONS: Our results demonstrated that metabolic flexibility was more remarkable in C. sinenis than in C. grandis roots, thus improving the Al-tolerance of C. sinensis. This provided the most integrated view of the adaptive responses occurring in Al-toxicity roots.

Boron-deficiency-responsive microRNAs and their targets in Citrus sinensis leaves.

BACKGROUND: MicroRNAs play important roles in the adaptive responses of plants to nutrient deficiencies. Most research, however, has focused on nitrogen (N), phosphorus (P), sulfur (S), copper (Cu) and iron (Fe) deficiencies, limited data are available on the differential expression of miRNAs and their target genes in response to deficiencies of other nutrient elements. In this study, we identified the known and novel miRNAs as well as the boron (B)-deficiency-responsive miRNAs from citrus leaves in order to obtain the potential miRNAs related to the tolerance of citrus to B-deficiency. METHODS: Seedlings of 'Xuegan' [Citrus sinensis (L.) Osbeck] were supplied every other day with B-deficient (0 µM H3BO3) or -sufficient (10 µM H3BO3) nutrient solution for 15 weeks. Thereafter, we sequenced two small RNA libraries from B-deficient and -sufficient (control) citrus leaves, respectively, using Illumina sequencing. RESULTS: Ninety one (83 known and 8 novel) up- and 81 (75 known and 6 novel) down-regulated miRNAs were isolated from B-deficient leaves. The great alteration of miRNA expression might contribute to the tolerance of citrus to B-deficiency. The adaptive responses of miRNAs to B-deficiency might related to several aspects: (a) attenuation of plant growth and development by repressing auxin signaling due to decreased TIR1 level and ARF-mediated gene expression by altering the expression of miR393, miR160 and miR3946; (b) maintaining leaf phenotype and enhancing the stress tolerance by up-regulating NACs targeted by miR159, miR782, miR3946 and miR7539; (c) activation of the stress responses and antioxidant system through down-regulating the expression of miR164, miR6260, miR5929, miR6214, miR3946 and miR3446; (d) decreasing the expression of major facilitator superfamily protein genes targeted by miR5037, thus lowering B export from plants. Also, B-deficiency-induced down-regulation of miR408 might play a role in plant tolerance to B-deficiency by regulating Cu homeostasis and enhancing superoxide dismutase activity. CONCLUSIONS: Our study reveals some novel responses of citrus to B-deficiency, which increase our understanding of the adaptive mechanisms of citrus to B-deficiency at the miRNA (post-transcriptional) level.

Identification of boron-deficiency-responsive microRNAs in Citrus sinensis roots by Illumina sequencing.

BACKGROUND: Boron (B)-deficiency is a widespread problem in many crops, including Citrus. MicroRNAs (miRNAs) play important roles in nutrient deficiencies. However, little is known on B-deficiency-responsive miRNAs in plants. In this study, we first identified miRNAs and their expression pattern in B-deficient Citrus sinensis roots by Illumina sequencing in order to identify miRNAs that might be involved in the tolerance of plants to B-deficiency. RESULTS: We isolated 52 (40 known and 12 novel) up-regulated and 82 (72 known and 10 novel) down-regulated miRNAs from B-deficient roots, demonstrating remarkable metabolic flexibility of roots, which might contribute to the tolerance of plants to B-deficiency. A model for the possible roles of miRNAs in the tolerance of roots to B-deficiency was proposed. miRNAs might regulate the adaptations of roots to B-deficiency through following several aspects: (a) inactivating reactive oxygen species (ROS) signaling and scavenging through up-regulating miR474 and down-regulating miR782 and miR843; (b) increasing lateral root number by lowering miR5023 expression and maintaining a certain phenotype favorable for B-deficiency-tolerance by increasing miR394 expression; (c) enhancing cell transport by decreasing the transcripts of miR830, miR5266 and miR3465; (d) improving osmoprotection (miR474) and regulating other metabolic reactions (miR5023 and miR821). Other miRNAs such as miR472 and miR2118 in roots increased in response to B-deficiency, thus decreasing the expression of their target genes, which are involved in disease resistance, and hence, the disease resistance of roots. CONCLUSIONS: Our work demonstrates the possible roles of miRNAs and related mechanisms in the response of plant roots to B-deficiency.

Reducing the contaminant dispersion and infection risks in the train cabins by adjusting the inlet turbulence intensity: A study based on turbulence simulation.

Existing studies on ventilation in closed spaces mainly considered the average inlet velocity and ignored the influence of inlet turbulent fluctuation. However, the variation in inlet turbulence intensity (TI) is considerable and significantly affects the dispersion of contaminants. This study conducts numerical simulations verified by experiments to investigate the effect of the inlet TI on train contaminants dispersion and analyze infection probability variation. Firstly, the unsteady Reynolds-averaged Navier-Stokes (URANS) method and improved delayed detached eddy simulation (IDDES) method are compared in simulating the internal airflow characteristics based on the on-site measurement. The results indicate that the latter dominates in capturing airflow pulsations more than the former, although the mean airflow results obtained from both methods agree well with experimental results. Furthermore, the IDDES method is employed to investigate the effect of the inlet TI on contaminant dispersion, and the infection risks are also assessed using the improved probability model. The results show that, with the increase of TI from 5 % to 30 %, the contaminant removal grows considerably, with the removal index rising from 0.23 to 1.86. The increased TI leads to the overall and local infection risks of occupants descending significantly, wherein the former decreases from 1.53 % to 0.88 % with a reduction rate of 42 %, and the latter drops from 3.30 % to 2.16 % with a mitigation rate of 35 %. The findings can serve as solid guidelines for numerical method selection in accurately capturing the indoor dynamic airflow distribution and for the ventilation parameters design regarding TI inside trains to mitigate the airborne infection risk.

Numerical computation of preimage domains for spiral slit regions and simulation of flow around bodies.

In this paper, we propose the iterative numerical methods to calculate the conformal preimage domains for the specified logarithmic spiral slit regions and develop the applications of conformal mappings in the simulations of the flow around bodies. Firstly, we postulate that the boundaries of the preimage domains mapped onto logarithmic spiral slits are ellipses. The lengths of the long axes of ellipses and the coordinates of the centers are calculated using our iterative methods. Secondly, each type of the presented iterative method calculates numerical conformal mappings via solving the boundary integral equation with the generalized Neumann kernel. Finally, numerical examples show the convergence and availability of our iterative methods and display the simulations of the flow around the bodies as an application.

Simulation and optimization of the thermal sterilization process of puree cans using the production of chestnut puree as an example.

In the production process of puree cans such as chestnuts cans, it is easy to browning due to excessive heating, which causes a lot of waste every year. The heat and mass transfer model of Chinese Chestnut Puree was established through the finite element method. The model simulated the change process of the temperature field, heat flow velocity field and F value during the production of Chinese Chestnut Puree. After comparing and confirming the effectiveness of the model through the thermal penetration test, the model was used to adjust and optimize the production process. For #9121 cans, the two-stage sterilization method was adopted. Through the sterilization method at 10-65-48-14/118-110°C, a sterilization effect equivalent to that of the original process at 10-86-24/121°C was achieved, the browning problem of the product was alleviated, and the product quality was improved. This practice can also provide a reference for canning enterprises to adjust their production processes in the future.

Research Progress of Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is a new infectious disease first discovered in Ta-pieh Mountains in central China in 2009. It is caused by a novel bunyavirus infection (SFTSV). Since the first discovery of SFTSV, there have been case reports and epidemiological studies on SFTS in several East Asian countries, such as South Korea, Japan, Vietnam and so on. With the rising incidence of SFTS and the rapid spread of the novel bunyavirus around the world, it is clear that the virus has a pandemic potential and may pose a threat to global public health in the future. Early studies have suggested that ticks are an important medium for the transmission of SFTSV to humans; in recent years, it has been reported that there is also human-to-human transmission. In endemic areas, potential hosts include a variety of livestock and wildlife. When people are infected with SFTV, the main clinical manifestations are high fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, liver and kidney function damage, and even MODS, with a mortality rate of about 10-30%. This article reviews the latest progress of novel bunyavirus, including virus transmission vector, virus genotypic diversity and epidemiology, pathogenesis, clinical manifestation and treatment.

Atomization Characteristics of Hydrogen Peroxide Solutions in Electrostatic Field.

Hydrogen peroxide (H2O2) can be considered as a sterilant or a green propellant. For a common use in industrial application, spray is an effective method to form fine H2O2 droplets. In this paper, electrostatic atomization based on the configuration of needle ring electrodes is proposed to produce H2O2 spray by minimizing its effective surface tension. The breakup performances of H2O2 ligaments can be improved by increasing the electric field intensity, reducing the nozzle size, and adjusting suitable volume flow rate. The smallest average diameter of breakup droplets for 35 wt. % concentration H2O2 solution reached 92.8 µm under optimum operation conditions. The H2O2 concentration significantly influenced the breakup performance owing to the concentration effect on comprehensive physical properties such as density, surface tension, viscosity, and permittivity. The average diameters of breakup droplets decreased with decreasing H2O2 concentration. At 8 wt. % concentration, the average breakup droplet diameter was reduced to 67.4 µm. Finally, electrostatic atomization mechanism of H2O2 solution was analyzed by calculating dimensionless parameters of Re, We, and Oh numbers with the combination of the operation conditions and physical properties for in-depth understanding the breakup behaviors. The calculation showed that the minimum average diameter of breakup droplets was obtained at 8 wt. % concentration at the investigated range of H2O2 concentration, which kept in agreement with the experimental results.

Photoanode-supported cathodic immunosensor for sensitive and specific detection of human chorionic gonadotropin.

Target biomarker detection with high accuracy in biological sample is necessary for the constructed immunoassays. Herein, a novel and enhanced cathodic immunosensor supported by photoanode was designed for sensitive and specific detection of human chorionic gonadotropin (HCG). Specifically, the electrode of TiO2 nanotube with N doping (TiO2:N) was fabricated and assembled with AgInS2 quantum dots (QDs) to acquire the TiO2:N/AgInS2 photoanode. For the sensing cathode, Pt nanoparticles (NPs) were decorated on carbon nanotubes (CNTs) to prepare the CNT/Pt cathodic matrix and was used to modify capture HCG antibody (Ab). In this photoelectrochemical (PEC) sensing system, the TiO2:N/AgInS2 photoanode served as the signal-converting element to produce prominent current signal, while the immune recognition events occurred on the sensing cathode to evidently change the initial current signal from steric hindrance effect. Profiting by excellent photoelectric property and good anti-interference ability of this featured PEC system, the developed cathodic immunosensor demonstrated high sensitivity and specificity for the detection of target HCG antigen (Ag). This photoanode-supported cathodic sensing strategy provided a potential path forward to exploit other enhanced PEC immunosensors in the application of biological samples.

High-performance photoelectrochemical immunosensor based on featured photocathode-photoanode operating system.

Photocathodic immunosensors generally exhibit fortified anti-interference abilities than photoanodic ones against the detection in biological specimens. Yet, the weak photocurrent signals of the photocathodes have limited evidently the detection performance. Herein, an efficient and feasible photoelectrochemical (PEC) immunosensor was developed on the basis of the featured photocathode-photoanode operating system. In the proposal, the elaborated PEC immunosensor integrated photocathode with photoanode, and the immune recognition occurred just on the photocathode. To illustrate the performance, α-fetoprotein (AFP) was selected as a target antigen (Ag) for detection. TiO2 nanoparticles were decorated with AgInS2 quantum dots (AIS QDs) to fabricate the TiO2/AIS photoanode, and the carbon nanotubes (CNTs) were modified with CuInS2 nanoflowers (CIS NFs) to prepare the CNT/CIS photocathode for the capture AFP antibody (Ab) anchoring. Target Ag detection depended on significant decrease of the photocurrent signal produced by large steric hindrance of the captured AFP molecules. Coupling excellent photoelectric property with anti-interference ability in this elegant PEC immunosensor, sensitive and specific probing of target Ag was realized. The proposed photocathode-photoanode integrating strategy provides a promising way to explore other high-performance PEC immunosensors against the detection in biological matrixes.

Effects of Gabexate Mesylate on the Gut Microbiota and Metabolomics in Rats with Sepsis.

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. However, there is still no single drug that could reduce septic mortality. Previous studies have reported gabexate mesylate (GM) significantly reduced serum inflammatory factors, alleviated sepsis-induced lung injury and improved clinical outcomes. This study aimed to combine with microbiome sequencing and metabolomics analysis to explore the effects of GM administration in septic rats. Methods: Sixty SD rats were randomly divided into the sham control (SC), cecal ligation and puncture (CLP), and GM injection (GM) groups. The mortality was measured and colonic feces were collected to examine the gut microbiota and metabolism 24 h after the procedure. The lung tissues were collected for hematoxylin-eosin staining. Results: We observed the relative abundance of Pygmaiobacter, which contributed to short-chain fatty acids (SCFAs) promotion, Lactobacillus and Erysipelotrichaceae UCG-003 increased in the GM-treated rats, while Escherichia-Shigella and Akkermansia decreased compared to the sepsis-induced lung injury group. Furthermore, these 3 metabolites including Palmitoylethanolamide, Deoxycholic acid and Chenodeoxycholic acid correlated significantly to CLP- and GM-rich genus (P < 0.05). Besides, the lung tissues of CLP group showed more severe inflammatory infiltration and edema, and the mortality rate in the CLP group (10/20) was significantly higher than in the SC group (0/20) (P < 0.001) and GM group (4/20) (P < 0.05). Conclusion: Our findings showed that GM attenuated sepsis-induced lung injury rats and regulated metabolites related to gut microbiota, which may provide an effective treatment for sepsis patients.

Citrus Physiological and Molecular Response to Boron Stresses.

Since the essentiality of boron (B) to plant growth was reported nearly one century ago, the implication of B in physiological performance, productivity and quality of agricultural products, and the morphogenesis of apical meristem in plants has widely been studied. B stresses (B deficiency and toxicity), which lead to atrophy of canopy and deterioration of Citrus fruits, have long been discovered in citrus orchards. This paper reviews the research progress of B stresses on Citrus growth, photosynthesis, light use efficiency, nutrient absorption, organic acid metabolism, sugar metabolism and relocation, and antioxidant system. Moreover, the beneficial effects of B on plant stress tolerance and further research in this area were also discussed.