Screening of high-efficiency nitrogen-fixing bacteria from the traditional Chinese medicine plant Astragalus mongolicus and its effect on plant growth promotion and bacterial communities in the rhizosphere.

BACKGROUND: Astragalus mongolicus Bunge is used in traditional Chinese medicine and is thus cultivated in bulk. The cultivation of A. mongolicus requires a large amount of nitrogen fertilizer, increasing the planting cost of medicinal materials and polluting the environment. Isolation and screening of plant growth-promoting rhizobacteria (PGPR) and exploring the nitrogen fixation potential of A. mongolicus rhizosphere microorganisms would effectively reduce the production cost of A. mongolicus. RESULTS: This study used A. mongolicus roots and rhizosphere soil samples from Longxi County of Gansu Province, Jingle County, and Hunyuan County of Shanxi Province, China, to isolate and identify nitrogen-fixing bacteria. Through nitrogen fixation efficiency test, single strain inoculation test, and plant growth-promoting characteristics, three strains, Bacillus sp. J1, Arthrobacter sp. J2, and Bacillus sp. G4 were selected from 86 strains of potential nitrogen-fixing bacteria, which were the most effective in promoting the A. mongolicus growth and increasing the nitrogen, phosphorus, and potassium content in plants. The antagonistic test showed that these bacteria could grow smoothly under the co-culture conditions. The J1, J2, and G4 strains were used in a mixed inoculum and found to enhance the biomass of A. mongolicus plants and the accumulation of the main medicinal components in the field experiment. Mixed bacterial agent inoculation also increased bacterial diversity and changed the structure of the bacterial community in rhizosphere soil. Meanwhile, the relative abundance of Proteobacteria increased significantly after inoculation, suggesting that Proteobacteria play an important role in plant growth promotion. CONCLUSIONS: These findings indicate that specific and efficient PGPRs have a significant promoting effect on the growth of A. mongolicus, while also having a positive impact on the structure of the host rhizosphere bacteria community. This study provides a basis for developing a nitrogen-fixing bacterial fertilizer and improving the ecological planting efficiency of A. mongolicus.

Long-non-coding RNA AK001058: A genetic biomarker in cisplatin sensitivity of non-small-cell lung carcinoma.

Previous evidences have shown that lncRNA AK001058 serves as an oncogene. This study aims to elucidate the expression characteristic of AK001058 in NSCLC samples, and its potential influence on the malignant progression and cisplatin resistance of NSCLC. Relative levels of AK001058 and IGF2 in NSCLC and non-tumoral tissues were detected by qRT-PCR. Proliferation inhibition rate and migratory rate in DDP-induced SPC-A1 and A549 cells were examined by CCK-8 and Transwell assay, respectively. Subsequently, DDP-resistant SPC-A1 and A549 cell lines were generated, and the role of AK001058 in affecting their cell phenotypes was determined. Using dual-luciferase reporter assay, the binding relationship between AK001058 and IGF2 was verified. Their co-regulation on DDP-resistant NSCLC cells was finally explored via rescue experiments. AK001058 was upregulated in NSCLC samples. The proliferative rate was dose-dependently and time-dependently declined in DDP-induced SPC-A1 and A549 cells. Cisplatin induction upregulated AK001058 in NSCLC cells, and attenuated migratory potential. Transfection of sh-AK001058 reduced proliferative and migratory rates in SPC-A1/DDP and A549/DDP cells. IGF2 was the downstream target binding AK001058, which was lowly expressed in NSCLC samples. AK001058 upregulation in NSCLC reduces cisplatin sensitivity and promotes malignant progression by negatively regulating IGF2, leading to cisplatin resistance.

[Association between early-life factors and pubertal timing in girls]. / ç”Ÿå‘½æ—©æœŸå› ç´ ä¸Žå¥³ç”Ÿé’æ˜¥å‘åŠ¨æ—¶ç›¸çš„å ³è”åˆ†æž.

OBJECTIVES: To study the association between early-life factors (including birth weight, method of birth, gestational age, and history of gestational metabolic disorders) and pubertal timing in girls. METHODS: The stratified cluster sampling method was used to select the girls in grades 2-3 and 7-8 from three primary schools and three middle schools in Guangzhou, China from March to December, 2019, and breast development was examined for all girls. A questionnaire survey was performed to collect the information on early-life factors. The multivariate logistic regression model was used to evaluate the association of gestational metabolic disorders, birth weight, method of birth, and gestational age with pubertal timing in girls. The Bootstrap method was used to assess the mediation effect of body mass index (BMI) (Z score) between high birth weight (≥4 000 g) and pubertal timing. RESULTS: A total of 1 665 girls were enrolled, among whom 280 (16.82%) were judged to have early pubertal timing. The multivariate logistic regression analysis showed that high birth weight was associated with the increased risk of early pubertal timing (OR=2.12, 95%CI: 1.19-3.66, P=0.008). Nevertheless, no significant association was observed between other early-life factors and pubertal timing (P>0.05). The OR for the mediation effect of BMI (Z score) between high birth weight and early pubertal timing was 1.25 (95%CI: 1.09-1.47), accounting for 29.33% of the total effect of high birth weight on early pubertal timing. CONCLUSIONS: High birth weight is associated with the increased risk of early pubertal timing in girls, and overweight/obesity may play a partial mediating role in the association between high birth weight and early pubertal timing in girls.

A Novel PCR Method for Detecting ACE Gene Insertion/Deletion Polymorphisms and its Clinical Application.

BACKGROUND: Angiotensin-converting enzyme (ACE) plays a major role in blood pressure regulation and cardiovascular homeostasis. The wide distribution and multifunctional properties of ACE suggest it's involvement in various pathophysiological conditions. RESULTS: In this study, a novel visual detection method for ACE I/D polymorphisms was designed by integrating direct PCR without the need for DNA extraction using gold magnetic nanoparticles (GMNPs)-based lateral flow assay (LFA) biosensor. The entire detection procedure could enable the genotyping of clinical samples in about 80 min. The detection limit was 0.75 ng and results could be obtained in 5 min using the LFA device. Three hundred peripheral blood samples were analyzed using the direct PCR-LFA system and then verified by sequencing to determine accuracy and repeatability. A clinical preliminary study was then performed to analyze a total of 633 clinical samples. CONCLUSIONS: After grouping based on age, we found a significant difference between the genotypes and the age of patients in the CHD group. The introduction of this method into clinical practice may be helpful for the diagnosis of diseases caused by large fragment gene insertions/deletions.

Integration of metabolomics and transcriptomics indicates changes in MRSA exposed to terpinen-4-ol.

BACKGROUND: This study investigated the effects of terpinen-4-ol on methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm, and the possible mechanisms governing this effect. RESULTS: We observed that terpinen-4-ol has good antibacterial activity and inhibits the formation of MRSA biofilm. The MIC and MBC values for terpinen-4-ol against S. aureus were 0.08% ~ 0.32%. And terpinen-4-ol at 0.32% could kill all bacteria and clear all biofilms. Untargeted metabolomic and transcriptomic analyses showed that terpinen-4-ol strongly inhibited DNA and RNA biosynthesis in MRSA at 2 h after treatment by affecting genes and metabolites related to purine and pyrimidine metabolic pathways. Some differential genes which play important roles in DNA synthesis and the production of eDNA from biofilm exposed to terpinen-4-ol was also significantly decreased compared with that of the control. CONCLUSIONS: Terpinen-4-ol has good antibacterial activity and significantly inhibits the formation of MRSA biofilm by inhibiting purine and pyrimidine metabolism.

Degradation of trimethoprim in aqueous by persulfate activated with nanosecond pulsed gas-liquid discharge plasma.

The persulfate activation by nanosecond pulsed gas-liquid discharge (NPG-LD) is employed to degrade the trimethoprim (TMP) in water. The results show that persulfate addition enhances the degradation of TMP by NPG-LD through an obvious synergetic effect. With treatment time of 50 min, the high removal efficiency and energy yield reach 94.6% and 0.57 gkWh-1 in air NPG-LD with the addition of persulfate, respectively, which is 13.5% and 0.09 gkWh-1 higher than that in solo air NPG-LD, respectively. Correspondingly, the calculated synergetic factor achieves 1.62, indicating the synergetic effect is established. The activation mechanism of persulfate by NPG-LD is analyzed by the measurement of reactive species and the effects of radical scavenger addition on TMP removal. It is found that the synergetic effect between NPG-LD and persulfate is attributed to the increased production of OH, H2O2, and . Besides, the TMP degradation by NPG-LD and persulfate synergetic system is influenced by discharge working gas, pulse voltage, addition dosage of persulfate, initial TMP concentration, and initial pH value. Subsequently, the degradation pathway of TMP is analyzed using LC-MS/MS.

Bencycloquidium bromide nasal spray is effective and safe for persistent allergic rhinitis: a phase III, multicenter, randomized, double-blinded, placebo-controlled clinical trial.

PURPOSE: To investigate the efficacy and safety of bencycloquidium bromide nasal spray (BCQB) in patients with persistent allergic rhinitis (PAR). METHODS: We enrolled 720 patients from 15 hospitals across China and randomly assigned them into BCQB group or placebo group (90 µg per nostril qid) to receive a 4-week treatment. Visual analog scale (VAS) for rhinorrhea, sneezing, nasal congestion, itching and overall symptoms were recorded by patients every day. Anterior rhinoscopy scoring was completed by doctors on every visit. Adverse events were recorded in detail. RESULTS: A total of 354 and 351 patients were included in BCQB group and in placebo group. Baseline information was comparable. At the end of the trial, the decrease of VAS for rhinorrhea from baseline was 4.83 ± 2.35 and 2.46 ± 2.34 in BCQB group and placebo group, respectively (P < 0.001). The change ratio from baseline of VAS for rhinorrhea in BCQB group was 72.32%, higher than 31.03% in placebo group (P < 0.001). VAS for other symptoms and overall symptoms also improved significantly in the BCQB group, while no inter-group difference was found in anterior rhinoscopy scoring. The incidence of adverse reaction was similar between the two groups. Most reactions were mild and no severe reactions happened. CONCLUSION: 90 µg BCQB per nostril four times daily is effective and safe in the treatment of rhinorrhea as well as sneezing, nasal congestion and itching for patients with PAR. RETROSPECTIVELY REGISTERED: ChiCTR2000030924, 2020/3/17.

A new pleuromutilin candidate with potent antibacterial activity against Pasteurella multocida.

This study assessed the antimicrobial activity of 14-O-[(4,6-Diaminopyrimidine-2-yl) thioacetyl] mutilin (DPTM), a novel pleuromutilin candidate with a substituted pyrimidine moiety, against Pasteurella multocida. Minimum Inhibitory Concentration (MIC), Oxford Cup assay, and time-kill experiments were used to measure the activity of DPTM against P. multocida serotype A in vitro. We observed that DPTM was potent against Pasteurella multocida serotype A with the MIC value of 0.781 µg/mL. The mean inhibition-zone diameters of DPTM (50, 25, and 12.5 µg/mL) were 29.4, 24.2 and 20.1 mm, respectively. Time-kill experiments showed that the drug caused a rapid decline in the number of bacteria compared with the initial inoculum at 4 h and killed 94.6% of the bacteria during 24 h. Furthermore, DPTM activity was also assessed in a lung infection model challenged with 4.0 × 109 CFU/mL P. multocida serotype A. The results showed that DPTM significantly reduced mortality rate and bacterial load, and alleviated the pathological changes of lung. The antibacterial effect of DPTM found in this study suggested that it was useful in the prevention or control of pneumonia caused by P. multocida.

Direct genotyping from whole blood using alkaline polyethylene glycol.

In order to simplify biological sample preparation to meet the demand of rapid genotyping, we improve alkaline polyethylene glycol (APEG) based on Chomczynski's procedure for the PCR-based lateral flow genotyping system, which enables the rapid and efficient direct genotyping from whole blood without DNA purification. The improved APEG has a high tolerance for extreme storage conditions. Testing whole blood with an abnormal hematological index indicates that APEG efficiency would not be influenced by pathological factors. Compared with sequencing, the accuracy of this genotyping system was 100% on testing with 200 clinical samples.

A Validated HPLC-MS/MS Assay for 14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] Mutilin in Biological Samples and Its Pharmacokinetic, Distribution and Excretion via Urine and Feces in Rats.

14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] mutilin (DPTM), a novel pleuromutilin candidate with a substituted pyrimidine moiety, has been confirmed to possess excellent antibacterial activity against Gram-positive bacteria. To illustrate the pharmacokinetic profile after intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations with DPTM, as well as tissue distribution and excretion via urine and feces in vivo, a specific, sensitive and robust HPLC-MS/MS method was first developed to determine DPTM in rat plasma, various tissues, urine and feces. The plasma, tissues, urine and feces samples were treated by protein precipitation with acetonitrile using tiamulin fumarate as an internal standard (IS). This method which was achieved on an HPLC system detector equipped with an ESI interface, was sensitive with 5 ng/mL as the lower limit of detection and exhibited good linearity (R² > 0.9900) in the range of 5⁻4000 ng/mL for plasma, various tissues, urine and feces, as well as intra-day precision, inter-day precision and accuracy. The matrix effects ranged from 94.2 to 109.7% with RSD ≤ 9.4% and the mean extraction recoveries ranged from 95.4 to 109.5% in plasma, tissue homogenates, urine and feces (RSD ≤ 9.9). After i.v., i.m. and p.o. administrations, DPTM was rapidly absorbed and metabolized in rats with the half-life (t1/2) of 1.70⁻1.86, 3.23⁻3.49 and 4.38⁻4.70 for 10, 25 and 75 mg/kg doses, respectively. The tissue distribution showed that DPTM was diffused into all the tested tissues, especially into the intestine and lung. Excretion via urine and feces studies demonstrated that DPTM was mainly excreted by feces after administration.

[Breeding of new Artemisia annua variety "Kehao No.1"].

As a natural plant source of artemisinin,a first-line drug against malaria,Artemisia annua directly affects the extraction process of artemisinin and the source of artemisinin. At present,traditional breeding methods combined with tissue culture are often used to breed high-yield artemisinin-containing new varieties of A. annua. However,the breeding method has the disadvantages of low efficiency and continuous selection. In this study,heavy ion beam irradiation technology was used to observe the specific germplasm resources of A. annua,and the morphological characteristics,agronomic traits and artemisinin content were used as indicators to observe the selection materials and materials. The cultivated new varieties were compared with trials and regional trials. In addition,the new variety of A. annua was identified by SRAP molecular marker technology. The results showed that the new variety of A. annua, " Kehao No.1",had an average yield of 235. 0 kg of dry leaf per mu,which was more than 20% higher than that of the control. Especially,the average artemisinin content was 2. 0%,which was 45% higher than that of the control,and the " Kehao No.1" has high anti-white powder disease,high-yield and high-quality new varieties. Therefore,mutagenic breeding of heavy ion beam irradiation can significantly improve the yield and artemisinin content of the " Kehao No. 1" and it has a good promotion value.

Antibacterial activity and pharmacokinetic profile of a promising antibacterial agent: 14-O-[(4-Amino-6-hydroxy-pyrimidine-2-yl)thioacetyl] mutilin.

A new pleuromutilin derivative, 14-O-[(4-Amino-6-hydroxy-pyrimidine-2-yl)thioacetyl] mutilin (APTM), has been synthesized and proved most potent antibacterial agent in in vitro assays, suggesting that further development of this compound may lead to a promising antibacterial drug. In this study, we further evaluated the cytotoxicity, antibacterial efficacy and the pharmacokinetic profile of APTM. In BRL 3A cells, 50% of viability was obtained when 363µg/mL of APTM was used, while retapamulin and tiamulin fumarate needed 49 and 28µg/mL, respectively, to reach this viability. Compared to tiamulin fumarate, APTM showed higher inhibition efficacy and faster bactericidal activity against S. aureus and lower 50% effective dose (ED50) in mice after a lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA). Docking experiment for APTM showed a similar binding pattern with tiamulin. Furthermore, a simple, accurate and sensitive HPLC method for the determination of APTM in rabbit plasma was developed and successfully applied to pharmacokinetic study, in which the half life (t1/2), clearance rate (Cl) and the area under the plasma concentration-time curve (AUC0→∞) were 3.37h, 0.35L/h/kg and 70.68µg·h/m, respectively.

Body image as risk factor for emotional and behavioral problems among Chinese adolescents.

BACKGROUND: Being overweight and obesity during adolescence are worldwide public health problems. This study examined the relationship between actual weight, body image, and emotional and behavioral problems among Chinese adolescents. METHODS: A total of 3841 adolescents (age range, 11-16 years) from 5 Chinese cities were included in this cross-sectional study. All of the study participants were asked to complete questionnaires (including demographic features, strengths and difficulties questionnaires, pubertal development scale), and their height and weight were measured at the same time. Body image was measured in two ways: self-perceived weight and body satisfaction. The relationship between weight status and mental health was estimated by multivariate logistic regression for boys and girls. RESULTS: Our study showed a difference by sex for prevalence of being overweight/obesity and body dissatisfaction among Chinese adolescents. Boys were more likely to be overweight or obese than girls (30.4% vs. 21.5%, p < 0.05), but girls were more likely to be dissatisfied with their bodies than boys (41.2% vs. 27.9%, p < 0.05). In the logistic regression, body image, not actually being overweight, was significantly associated with a higher risk of emotional and behavioral problems. Compared to perceived normal weight boys, boys who perceived themselves as underweight had an increased likelihood of emotional problems (adjusted odds ratio [OR] = 1.73; 95% confidence interval (CI), 1.16-2.57), conduct problems (OR = 1.73; 95% CI, 1.20-2.50), and total difficulties (OR = 1.50; 95% CI, 1.09-2.05). Compared to body satisfaction, body dissatisfaction was a risk factor for emotional problems (boys: OR = 2.80; 95% CI, 1.84-4.25; girls: OR = 2.18; 95% CI, 1.42-3.36), conduct problems (boys: OR = 1.87, 95% CI, 1.26-2.76; girls: OR = 2.79; 95% CI, 1.46-5.30), hyperactivity problems (boys: OR = 1.67; 95% CI, 1.09-2.55; girls: OR = 2.04; 95% CI, 1.13-3.69), and total difficulties (boys: OR = 2.03; 95% CI, 1.45-2.84; girls: OR = 2.30; 95% CI, 1.46-3.56). CONCLUSIONS: Being overweight and obese during adolescence are very serious public health problems in China. Body image was a more substantial predictor for adolescent emotional and behavioral problems than actually being overweight/obesity.

Synthesis and antibacterial activities of novel pleuromutilin derivatives.

Pleuromutilin derivatives 4a-h, 5a-g, and 6a-d were synthesized and characterized by IR, 1 H NMR, and 13 C NMR. All synthetic compounds were screened for their in vitro antibacterial activity against Staphylococcus aureus (ATCC 25923), methicillin-resistant S. aureus (MRSA, ATCC 43300), Pasteurella multocida (CVCC 408), Escherichia coli (ATCC 25922), and Salmonella typhimurium (ATCC 14028). Most compounds with quaternary amine showed higher antibacterial activities against both Gram-positive and Gram-negative bacteria strains. Among the screened compounds, compound 5a bearing an N,N,N-trimethyl group at the C-14 side chain of pleuromutilin was found to be the most active agent. Furthermore, preliminary molecular docking was performed to predict the binding interaction of the compounds in the binding pocket.

Novel compound heterozygous mutations in the OTOF Gene identified by whole-exome sequencing in auditory neuropathy spectrum disorder.

BACKGROUND: Many hearing-loss diseases are demonstrated to have Mendelian inheritance caused by mutations in single gene. However, many deaf individuals have diseases that remain genetically unexplained. Auditory neuropathy is a sensorineural deafness in which sounds are able to be transferred into the inner ear normally but the transmission of the signals from inner ear to auditory nerve and brain is injured, also known as auditory neuropathy spectrum disorder (ANSD). The pathogenic mutations of the genes responsible for the Chinese ANSD population remain poorly understood. METHODS: A total of 127 patients with non-syndromic hearing loss (NSHL) were enrolled in Guangxi Zhuang Autonomous Region. A hereditary deafness gene mutation screening was performed to identify the mutation sites in four deafness-related genes (GJB2, GJB3, 12S rRNA, and SLC26A4). In addition, whole-exome sequencing (WES) was applied to explore unappreciated mutation sites in the cases with the singularity of its phenotype. RESULTS: Well-characterized mutations were found in only 8.7% (11/127) of the patients. Interestingly, two mutations in the OTOF gene were identified in two affected siblings with ANSD from a Chinese family, including one nonsense mutation c.1273C > T (p.R425X) and one missense mutation c.4994 T > C (p.L1665P). Furthermore, we employed Sanger sequencing to confirm the mutations in each subject. Two compound heterozygous mutations in the OTOF gene were observed in the two affected siblings, whereas the two parents and unaffected sister were heterozygous carriers of c.1273C > T (father and sister) and c.4994 T > C (mother). The nonsense mutation p.R425X, contributes to a premature stop codon, may result in a truncated polypeptide, which strongly suggests its pathogenicity for ANSD. The missense mutation p.L1665P results in a single amino acid substitution in a highly conserved region. CONCLUSIONS: Two mutations in the OTOF gene in the Chinese deaf population were recognized for the first time. These findings not only extend the OTOF gene mutation spectrum for ANSD but also indicate that whole-exome sequencing is an effective approach to clarify the genetic characteristics in non-syndromic ANSD patients.

Palladium-catalyzed intermolecular tandem cyclization reaction: a highly regioselective synthesis of functionalized 3H-spiro[isobenzofuran-1,3'-isochroman] scaffolds.

A highly regioselective synthesis of functionalized 3H-spiro[isobenzofuran-1,3'-isochroman] scaffolds using a novel palladium-catalyzed tandem cyclization reaction is explored. During the reaction process, C-O, C-C and C-O bonds are sequentially formed in one pot via decarboxylative allenylpalladium formation, nucleophilic attack, arylpalladium addition and intramolecular nucleophilic attack.

Strain improvement of Trichoderma viride for increased cellulase production by irradiation of electron and (12)C(6+)-ion beams.

OBJECTIVES: To improve cellulase production and activity, Trichoderma viride GSICC 62010 was subjected to mutation involving irradiation with an electron beam and subsequently with a (12)C(6+)-ion beam. RESULTS: Mutant CIT 626 was the most promising cellulase producer after preliminary and secondary screening. Soluble protein production and cellulase activities were increased mutifold. The optimum temperature, pH and culture time for the maximum cellulase production of the selected mutant were 35 °C, pH 5 and 6 days. The highest cellulase production was obtained using wheat bran. The prepared cellulases from T. viride CIT 626 had twice the hydrolytic performance with sawdust (83 %) than that from the parent strain (42.5 %). Furthermore, molecular studies demonstrated that there were some key mutation sites suggesting that some amino acid changes in the protein caused by base mutations had led to the enhanced cellulase production and activity. CONCLUSIONS: Mutagenesis with electron and (12)C(6+)-ion beams could be developed as an effective tool for improvement of cellulase producing strains.

Synthesis and Pharmacological Evaluation of Novel Pleuromutilin Derivatives with Substituted Benzimidazole Moieties.

A series of novel pleuromutilin derivatives with substituted benzimidazole moieties were designed and synthesized from pleuromutilin and 5-amino-2-mercaptobenzimidazole through sequential reactions. All the newly synthesized compounds were characterized by IR, NMR, and HRMS. Each of the derivatives was evaluated in vitro for their antibacterial activity against Escherichia coli (E. coli) and five Gram (+) inoculums. 14-O-((5-amino-benzimidazole-2-yl) thioacetyl) mutilin (3) was the most active compound and showed highest antibacterial activities. Furthermore, we evaluated the inhibition activities of compound 3 on short-term S. aureus and MRSA growth and cytochrome P450 (CYP). The bioassay results indicate that compound 3 could be considered potential antibacterial agents but with intermediate inhibition of CYP3A4.

Review of Platensimycin and Platencin: Inhibitors of ß-Ketoacyl-acyl Carrier Protein (ACP) Synthase III (FabH).

Platensimycin and platencin were successively discovered from the strain Streptomyces platensis through systematic screening. These natural products have been defined as promising agents for fighting multidrug resistance in bacteria by targeting type II fatty acid synthesis with slightly different mechanisms. Bioactivity studies have shown that platensimycin and platencin offer great potential to inhibit many resistant bacteria with no cross-resistance or toxicity observed in vivo. This review summarizes the general information on platensimycin and platencin, including antibacterial and self-resistant mechanisms. Furthermore, the total synthesis pathways of platensimycin and platencin and their analogues from recent studies are presented.

In vivo efficacy and toxicity studies of a novel antibacterial agent: 14-o-[(2-amino-1,3,4-thiadiazol-5-yl)thioacetyl] mutilin.

A new pleuromutilin derivative with excellent antibacterial activity, 14-O-[(2-amino-1,3,4-thiadiazol-5-yl) thioacetyl] mutilin (ATTM), may serve as a possible lead compound for the development of antibacterial drugs. However, in vivo efficacy and toxicity evaluations of this compound have not been performed. In this study, we evaluated the efficacy of ATTM by measuring the survival of mice after a lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA), and the 50% effective dose (ED50) was 5.74 mg/kg by the intravenous route. In an oral single-dose toxicity study, ATTM was orally administered to mice at different doses and the 50% lethal dose (LD50) was calculated to be 2304.4 mg/kg by the Bliss method. The results of the subchronic oral toxicity study in rats showed no mortality, exterior signs of toxicity, or differences in the total weight gain or relative organ weights between the treated groups and control group after administration. The hematological and serum biochemical data showed no differences between the treated and control groups, except for the levels of alkaline phosphatase (ALP), creatinine (CR) and blood glucose (GLU), which were significantly different in the high-dose group. The differences in the histopathological findings between the treated groups and the control group were not considered to be treatment-related. Our results indicated that the no observed adverse effect level (NOAEL) for ATTM was 5 mg/kg in this study.