The Gut Microbiome and Acute Leukemia: Implications for Early Diagnostic and New Therapies.

Acute leukemia (AL), one of the hematological malignancies, shows high heterogeneity. Tremendous progresses are achieved in treating AL with novel targeted drugs and allogeneic hematopoietic stem cell transplantation, there are numerous issues including pathogenesis, early diagnosis, and therapeutic efficacy of AL to be solved. In recent years, an increasing number of studies regarding microbiome have shed more lights on the role of gut microbiota in promoting AL progression. Mechanisms related to the role of gut microbiota in enhancing AL genesis are summarized in the present work, especially on critical pathways like leaky gut, bacterial dysbiosis, microorganism-related molecular patterns, and bacterial metabolites, resulting in AL development. Additionally, the potential of gut microbiota as the biomarker for early AL diagnosis is discussed. It also outlooks therapies targeting gut microbiota for preventing AL development.

Gut microbiota and metabolites in myasthenia gravis: Early diagnostic biomarkers and therapeutic strategies.

Myasthenia gravis (MG) is an acquired neurological autoimmune disorder characterized by dysfunctional transmission at the neuromuscular junction. The complex interplay of genetic and environmental influences is important for the occurrence and development of the disease. Recently, some studies have demonstrated the relationship between gut microbiota dysbiosis and MG. Certain gut microbial strains have been shown to attenuate or promote MG. This review summarized the role of gut microbiota and metabolites in MG progression. Meanwhile, we discuss the important potential of gut microbiota and metabolites for the early diagnostic biomarker of MG. Regulating gut microbiota may be novel and effective treatment for MG. Thus, targeted gut microbiota therapies are discussed and prospected to prevent MG progression.

The gut microbiome and Alopecia areata: Implications for early diagnostic biomarkers and novel therapies.

Alopecia areata (AA) accounts for the autoimmune disorder mediated by T cells, whose prognostic outcome cannot be predicted and curative treatment is unavailable at present. The AA pathogenic mechanism remains largely unclear, even though follicular attack has been suggested to result from that attack of immune privilege-losing hair follicles driven by immunity. Recently, gut microbiota is suggested to have an important effect on immunoregulation under autoimmune situations like AA. Fecal microbial transplantation (FMT) may be used to treat AA. Nonetheless, related research remains at the initial stage. To promote the rapid progress of relevant research, the present work aimed to shed more lights on gut microbiota's effect on AA, early diagnostic biomarker and FMT therapeutics.

Future Prospect of Oral Microbiota Influencing Allergy/Asthma Development.

Allergic diseases have become a primary public health issue in a moderately prosperous society. Colonization of microorganisms early in life appears to be significant in guiding the regulation of childhood immune system maturation and allergy development. Since the oral cavity is the first position where most foreign antigens meet the immune system, the oral microbiota may play a key role in the development of allergies. However, the study on the effects of oral microorganisms on allergy/asthma is very restricted and should be actively investigated. It requires considerable effort to enrich our knowledge in this area of the relationship between the oral cavity and allergy/asthma. To promote the rapid progress of relevant research. In this review, we aimed to provide several insights into the role of the oral microbiota in allergy/asthma while prospecting future directions.

Emergence of Hypervirulent ST11-K64 Klebsiella pneumoniae Poses a Serious Clinical Threat in Older Patients.

The carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses a severe therapeutic challenge to global public health, and research on CR-hvKP in older patients remain limited. In this study, we aimed to investigate the clinical and molecular characteristics and risk factors of CR-hvKP infections in older patients. We retrospectively investigated older patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in the intensive care unit (ICU) between January 2020 and December 2020. The clinical data, and microbiological data including antimicrobial susceptibility testing, phenotype experiment and detection of carbapenemases, string test, virulence genes, capsular serotype-specific (cps) genes, and multilocus sequence typing, of the CR-hvKP group defined by the presence of any one of the virulence genes, including rmpA, rmpA2, iucA, iroN, and peg-344 were compared with those of CR-non-hvKP strains. Of the 80 CRKP strains, 51 (63.8%) met the definition of CR-hvKP. The main mechanism of resistance to carbapenems was the presence of the blaKPC-2 gene. Sequence type (ST)11 (81.3%, 65/80) and ST15 (16.3%, 13/80) were the most common STs in CRKP strains. The minimum inhibitory concentration (MIC)50 values of the CR-hvKP group against the six tested antibiotics (ceftazidime, ceftazidime-avibactam, imipenem-avibactam, tigecycline, levofloxacin, and Cefoperazone-Sulbactam) exhibited elevated levels than the CR-non-hvKP group. Ceftazidime and imipenem by combining avibactam (4 µg/mL) significantly decreased the MIC90 values more than 16-fold than ceftazidime and imipenem alone against Klebsiella pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae. Cardiovascular disease [odds ratio (OR) = 11.956] and ST11-K64 (OR = 8.385) appeared to be independent variables associated with CR-hvKP infection by multivariate analysis. In conclusion, higher MICs of the last line antibiotic agents (ceftazidime-avibactam, tigecycline) might be a critical consideration in the clinical management of older patients where the concentration of these toxic antibiotics matters because of underlying comorbidities. Caution regarding KPC-2-producing ST11-K64 CR-hvKP as being new significant "superbugs" is required as they are widespread, and infection control measures should be strengthened to curb further dissemination in nosocomial settings in China.

First Report of Alfalfa Root Rot Caused by Plectosphaerella cucumerina in Inner Mongolia Autonomous Region of China.

Alfalfa (Medicago sativa L.) is an important forage crop with high nutrition for animal feed. In May 2016, a disease showing brown root rot was observed on alfalfa collected from several farms in Tongliao City (44°17' N; 121°29' E), Inner Mongolia Autonomous Region of China. The incidence of brown root rot was approximately 50 to 70% in the 2-year-old alfalfa field. Infected alfalfa exhibited varying degrees of decay in the tap root. Symptomatic roots were cut into 0.5-cm pieces, surface disinfected with 70% ethanol for 5 s and 0.1% HgCl2 for 35 s, then rinsed with sterilize distilled water three times, and placed onto potato dextrose agar (PDA) at 26°C in the dark. After 5 days, hyphal tips of the growing colonies were transferred onto PDA plates for purification. Forty-four isolates belonging to five fungal species were obtained from 20 diseased root samples. Six of the isolates resembled the genus Plectosphaerella. Colonies of these isolates were white to cream in color with sparse aerial mycelium, and then gradually became salmon pink with slimy or moist mycelium. The hyphae were transparent and branched. Colonies produced numerous hyphal coils with conidiophores. Conidiogenous cells and conidia were both hyaline, solitary, and smooth. Conidia were 4 to 8.5 ×1.2 to 4.8 µm (n= 100), 0 to 1 septum, elliptical and ovoid, and aggregating to form a head (Palm et al. 1995). According to these morphological characteristics, the fungus was identified as P. cucumerina (Lindf.) (Carlucci et al. 2012). To confirm the identification, the genomic DNA of two representative isolates was extracted and their internal transcribed spacer (ITS) region was amplified and sequenced with the primer pair ITS1/ITS4 (White et al. 1990). The ITS sequences of the two isolates were deposited in GenBank (acc. nos. MN915126 and MN915127). The two ITS sequences showed 99 to 100% identical to known P. cucumerina strains CBS 131739 (acc. no. KY662258.1) (Su et al. 2017) and MP313 (acc. no. KC756835.1) from alfalfa in China (Wen et al. 2015). To test for pathogenicity, a set of 15 alfalfa seedlings (cv. Aohan) were root-dipped in the conidial suspension of one of the isolates (1×105 conidia /ml) prepared from 7-day-old cultures on PDA. Inoculated seedlings were transplanted in three pots (10×15 cm) with sterilized nursery soil. Another set of five alfalfa seedlings inoculated with sterile water only served as the controls. Treated alfalfa seedlings were maintained in a greenhouse at 25°C to 28°C under a 12-h photoperiod. After 25 days, the roots of all inoculated plants showed brown lesions. P. cucumerina was reisolated from symptomatic tissue. No symptoms were observed on the control plants. P. cucumerina was previously reported on alfalfa in the fields of Huanxi Country (36°20' N; 107°21'), Gansu Province, China (Wen et al. 2015). To our knowledge, this is the first report of P. cucumerina causing root rot of alfalfa in Inner Mongolia Autonomous Region, China. This disease may cause serious economic losses in the region. It is needed to develop effective management strategies for control of this disease.

A rapid performance evaluation approach for lower mobility hybrid robot based on gravity-center position.

This article develops a rapid performance evaluation approach for lower mobility hybrid robot, which provides guidance for manipulator evaluation, design, and optimization. First, a general position vector model of gravity center for the lower mobility hybrid robot in the whole workspace is constructed based on a general inverse kinematic model. A performance evaluation index based on gravity-center position is then proposed, where the coordinates pointing to the supporting direction are selected as the evaluation index of the robot performance. Furthermore, the credibility of the evaluation approach is verified from a 5-DOF hybrid robot (TriMule) by comparing with the condition number and the first natural frequency. Analysis results demonstrate that the evaluation index can not only reflect the performance spatial distribution in the whole workspace but also is sensitive to the performance difference caused by mass distribution. The proposed performance evaluation approach provides a new index for the rapid design and optimization of the cantilever robot.

Coupling analysis of a 5-degree-of-freedom hybrid manipulator based on a global index.

Parallel kinematic machines have been applied in aerospace and automotive manufacturing due to their potentials in high speed and high accuracy. However, there exists coupling in parallel kinematic machines, which makes dynamic analysis, rigidity enhancement, and control very complicated. In this article, coupling characteristics of a 5-degree-of-freedom (5-dof) hybrid manipulator are analyzed based on a local index and a global index. First, velocity analysis as well as acceleration analysis of the robot is conducted to provide essential information for dynamic modeling. Then the dynamic model is built based on the principle of virtual work. Whereas the mass matrix is off-diagonal, a local coupling index as well as a global index is defined, based on which coupling characteristics of the robot are analyzed. Results show that distributions of coupling indices are symmetric due to its structural features. And dimensional parameters, structural parameters, as well as mass parameters have a large influence on the system's coupling characteristics. Research conducted in the article is of great help in optimal design and control. Meanwhile, the method proposed in the article can be applied to other types of parallel kinematic machines or hybrid manipulators.

Trajectory optimization of the 6-degrees-of-freedom high-speed parallel robot based on B-spline curve.

According to the problem that the existing high-speed parallel robot cannot satisfy the operation requirements of non-planar industrial production line, a 6-degrees-of-freedom high-speed parallel robot is proposed to carry out the kinematic and dynamic analyses. Combining with the door-type trajectory commonly used by the parallel robot, it adopts 3-, 5-, and 7-time B-spline curve motion law to conduct the trajectory planning in operation space. Taking the average cumulative effect of joint jerky as the optimization target, a trajectory optimization method is proposed to improve the smoothness of robot end-effector motion with the selected motion law. Furthermore, to solve the deformation problem of the horizontal motion stage of the trajectory, a mapping model between the control point subset of B-spline and the motion point subset of trajectory is established. Based on the main diagonally dominant characteristic of the coefficient matrix, the trajectory deformation evaluation index is constructed to optimize the smoothness and minimum deformation of the robot motion trajectory. Finally, compared to without the optimization, the maximum robot joint jerk decreases by 69.4% and 72.3%, respectively, and the maximum torque decreases by 51.4% and 38.9%, respectively, under a suitable trajectory deformation.

Studies on the binding of fulvic acid with transferrin by spectroscopic analysis.

Transferrin has shown potential in the delivery of anticancer drugs into primarily proliferating cancer cells that over-express transferrin receptors. Fulvic acid has a wide range of biological and pharmacological activities which caused widespread concerns, the interaction of fulvic acid with human serum transferrin (Tf) has great significance for gaining a deeper insight about anticancer activities of fulvic acid. In this study, the mechanism of interaction between fulvic acid and Tf, has been investigated by using fluorescence quenching, thermodynamics, synchronous fluorescence and circular dichroism (CD) under physiological condition. Our results have shown that fulvic acid binds to Tf and form a new complex, and the calculated apparent association constants are 5.04×10(8) M(-1), 5.48×10(7) M(-1), 7.38×10(6) M(-1) from the fluorescence quenching at 288 K, 298 K, and 310 K. The thermodynamic parameters indicate that hydrogen bonding and weak van der Waals are involved in the interaction between fulvic acid and Tf. The binding of fulvic acid to Tf causes the α-helix structure content of the protein to reduce, and resulting that peptide chains of Tf become more stretched. Our results have indicated a mechanism of the interaction between fulvic acid and Tf, which may provide information for possible design of methods to deliver drug molecules via transferrin to target tissues and cells effectively.