Red Blood Cell Lysis Pretreatment Can Significantly Improve the Yield of Treponema pallidum DNA from Blood.

PCR can be a supplement to Treponema serological testing. However, its sensitivity is not satisfactory for blood sample testing. The aim of this study was to investigate whether pretreatment with red blood cell (RBC) lysis could enhance the yield of Treponema pallidum subsp. pallidum DNA extraction from blood. We developed and verified the efficacy of a quantitative PCR (qPCR) assay that utilizes TaqMan technology to specifically detect T. pallidum DNA by targeting the polA gene. Simulation media with 106 to 100 treponemes/mL were prepared in normal saline (NS), whole blood, plasma, and serum, and RBC lysis pretreatment was performed on a portion of whole blood. Then, blood samples drawn from 50 syphilitic rabbits were divided in parallel into five groups, labeled whole blood, whole blood/lysed RBCs, plasma, serum, and blood cells/lysed RBCs. DNA extraction and qPCR detection were performed. The detection rate and copy number were compared among different groups. The polA assay showed good linearity and an excellent amplification efficiency of 102%. In the simulated blood samples, the detection limit of the polA assay reached 1 × 102 treponemes/mL in whole blood/lysed RBCs, plasma, and serum. However, the detection limit was only 1 × 104 treponemes/mL in NS and whole blood. Among the blood samples from syphilitic rabbits, whole blood/lysed RBCs showed the best detection rate (82.0%), while the detection rate for whole blood was only 6%. The copy number of whole blood/lysed RBCs was higher than that of whole blood. RBC lysis pretreatment can significantly improve the yield of T. pallidum DNA from whole blood, and the yield is better than that from whole blood, plasma, serum, and blood cells/lysed RBCs. IMPORTANCE Syphilis is a sexually transmitted disease caused by T. pallidum that can spread into the blood. T. pallidum DNA can be detected in blood by PCR but with low sensitivity. Few studies have applied RBC lysis pretreatment to blood T. pallidum DNA extraction. This study shows that the detection limit, detection rate, and copy number of whole blood/lysed RBCs were better than those of whole blood, plasma, and serum. After RBC lysis pretreatment, the yield of low concentrations of T. pallidum DNA was improved, and the low sensitivity of blood-based T. pallidum PCR was improved. Therefore, whole blood/lysed RBCs are the ideal sample for acquiring blood T. pallidum DNA.

Outcomes of radial head fractures treated with pre-curved metacarpal plate.

OBJECTIVE: To explore the clinical outcomes of MasonII/III radial head fractures without the neck involvement treated with pre-curved metacarpal plates. METHODS: Ninety cases of Mason typeII/III radial head fractures without the neck involvement were retrospectively collected from the department of orthopaedics of our hospital from September 2015 to May 2021. Group A (n = 44) underwent open reduction and internal fixation with pre-curved metacarpal plate, and Group B (n = 46) were fixed by traditional T-shaped plates. The operation time and the incision length were recorded during the operation. The Mayo Elbow Performance Score (MEPS), Disability of Arm, Shoulder and Hand (DASH) score, visual analogue scale (VAS) for pain, range of motion (ROM) and post-operative complications were evaluated at the last follow-up. RESULTS: All the patients were followed up for at least 12 months. There were no significant difference between two groups regarding operation time (54.2 ± 12.1 v.s 51.3 ± 7.2, mins), MEPS (88.9 ± 4.2 v.s 87.8 ± 4.4), DASH score (7.3 ± 4.6 v.s 9.0 ± 4.0), VAS (1.6 ± 0.8 v.s 1.7 ± 0.7), and ROM. However, the incision length was shorter in Group A (5.6 ± 0.5 v.s 6.6 ± 0.5, cm, P < 0.01). The postoperative complication rate was also lower in Group A (1/44 v.s 8/46, P = 0.02). CONCLUSION: Masson II/III radial head fractures without the neck involvement treated with pre-curved metacarpal plates could achieve satisfactory outcomes comparable to traditional T-shaped plates. Moreover, the invasiveness and postoperative complications are less in patients with pre-curved metacarpal plates. LEVEL OF EVIDENCE: III, retrospective comparison study.

Development and Evaluation of a Novel One-Step RT-qPCR Targeting the Vero Gene for the Identification of False-Positive Results Caused by Inactivated Virus Vaccine Contamination.

To identify false-positive SARS-CoV-2 test results caused by novel coronavirus inactivated vaccine contamination, a novel RT-qPCR targeting the ORF1ab and N genes of SARS-CoV-2 and Vero gene was developed. The amplification efficiency, precision, and lower limit of detection (LLOD) of the RT-qPCR assay were determined. A total of 346 clinical samples and 132 environmental samples were assessed, and the diagnostic performance was evaluated. The results showed that the amplification efficiency of the ORF1ab, N, and Vero genes was 95%, 97%, and 93%, respectively. The coefficients of variation of Ct values at a concentration of 3 × 104 copies/mL were lower than 5%. The LLOD for the ORF1ab, N, and Vero genes reached 8.0, 3.3, and 8.2 copies/reaction, respectively. For the 346 clinical samples, our RT-qPCR assay identified SARS-CoV-2-positive and SARS-CoV-2-negative samples with a sensitivity of 100.00% and a specificity of 99.30% and novel coronavirus inactivated vaccine-contaminated samples with a sensitivity of 100% and a specificity of 100%. For the environmental samples, our RT-qPCR assay identified novel coronavirus inactivated vaccine-contaminated samples with a sensitivity of 88.06% and a specificity of 95.38%. In conclusion, the RT-qPCR assay we established can be used to diagnose COVID-19 and, to a certain extent, false-positive results due to vaccine contamination.

Clinical effect of peroneal fracture line in the treatment of posterior Pilon fracture / 中华骨科杂志

Objective:To investigate the clinical effect of peroneal fracture line in the treatment of posterior Pilon fracture.Methods:The data of 26 patients treated with fibular fracture line from January 2017 to July 2019 were analyzed retrospectively, including 11 males and 15 females; the age ranged from 28 to 69 years, with an average of 42.2 years. There were 10 cases of falling injury, 9 cases of falling injury and 7 cases of traffic injury; all of them were fresh closed fibular fractures;According to Yu Guangrong's classification, there were 11 cases of type I, 8 cases of type II and 7 cases of type III; AGH was divided into 10 cases of type I, 5 cases of type IIa, 2 cases of type IIb, 5 cases of type IIIa and 4 cases of type IIIb. All cases were treated by opening the fibular fracture line through the posterolateral approach, the quality of fracture reduction was evaluated by Burwell Charnley radiological evaluation standard after operation; At the last follow-up, ankle function was evaluated by American Association of Foot and Ankle surgery (AOFAS) ankle and hindfoot scores.Results:All 26 patients were followed up for 12-23 months, with an average of 14.9 months; Bone healing was achieved in all fractures. The healing time was 3-6 months, with an average of 4.0 months. The quality of fracture reduction was evaluated according to the Burwell Charnley radiology evaluation standard after operation, including anatomical reduction in 23 cases and acceptable reduction in 3 cases. The anatomical reduction rate was 88% (23/26). At the last follow-up, AOFAS ankle and hindfoot scores ranged from 80 to 100, with an average of 89.9 points, of which 17 cases were excellent and 9 cases were good, and the excellent and good rate was 100%. At the last follow-up, no patient had complications such as reduction loss, skin necrosis, infection, internal fixation loosening or ankle stiffness.Conclusion:After the treatment of Pilon fractures via peroneal fracture line, the distal tibial articular surface and posterior ankle fracture gap can be fully exposed, which can be repositioned and fixed under direct vision, with high anatomical repositioning rate and good and safe clinical results.

Identifying FBLN1 (Gene ID: 2192) as a Potential Melanoma Biomarker for Melanoma based on an Analysis of microRNA Expression Profiles in the GEO and TCGA Databases.

Aims: We analyzed and compared the gene expression profiles (GSE92763) from normal melanocytes with malignant melanoma cell lines to identify genes that were differentially expressed that could serve as potential biomarkers for melanoma diagnosis. Materials and Methods: Gene expression profiles from the GSE92763 dataset were downloaded from the Gene Expression Omnibus (GEO) database. By comparing normal human melanocytes with multiple melanoma cell lines we identified 127 differentially expressed genes whose expression was altered. These data were used to identify hub genes associated with protein-protein interaction networks using Cytoscape software. To explore the biological functions of the aforementioned hub genes, we utilized the clusterProfiler package in R studio to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We then used the Gene Expression Profiling Interactive Analysis (GEPIA) website to determine the association of these hub genes with overall survival (OS). In addition, we utilized the Oncomine and Cancer Cell Line Encyclopedia (CCLE) databases to further analyze and compare the expression of these key genes associated with melanoma with other tumor types. Results: The hub genes included three upregulated and seven downregulated genes, which were linked with extracellular junctions, migration, paracrine and proliferation functions based on GO. In addition, we performed a confirmatory analysis of the hub genes using The Cancer Genome Atlas (TCGA) database. This analysis revealed that the expression of the Fibulin 1 (FBLN1; gene ID: 2192) gene was significantly downregulated in melanomas, and that its expression level in melanoma patients was significantly associated with OS with high expressors having better OS (log-rank p = 0.0034, hazard ratio = 1.5, p = 0.0036). We further analyzed the expression of FBLN1 in melanoma using the TCGA and Oncomine databases, and confirmed that FBLN1 is expressed at lower levels than in other cells (p = 2.03E-15, t = -15.586). FBLN1 has extremely high DNA copy number and low messenger RNA expression in melanoma cell lines according to the CCLE analysis. Conclusion: These results suggest that FBLN1 expression may be utilized as a biomarker and essential prognostic factor for melanoma; as well as provide an important theoretical basis for the development of melanoma treatments.

Protective effects of orally administered shark compound peptides from Chiloscyllium plagiosum against acute inflammation.

The anti-inflammatory effects of shark compound peptides (SCP) from Chiloscyllium plagiosum were investigated. Results showed that SCP enhanced the viability of RAW 264.7 macrophages in vitro in a dose-dependent manner. Orally administered SCP exhibited potent anti-inflammatory activity in lipopolysaccharide (LPS)-challenged mice by suppressing serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), as well as nitric oxide (NO). Moreover, SCP significantly inhibited the inflammatory rise of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatinine (CRE), while blocking the decline of cholinesterase (CHE), with an efficacy close to aspirin. This research showed that orally administered SCP from C. plagiosum notably downregulated uncontrolled inflammatory responses, and conferred substantial protection from endotoxin-induced acute hepatic damage and renal functional impairment. Therefore, oral supplementation of SCP can be used as a preventive approach to reduce the risk of inflammatory-related diseases.

The total terpenoids of Celastrus aggravate DNA damage and induce apoptosis of gastric cancer cells by inhibiting Chk1 / 中国药理学通报

Aim To explore the inhibitory effect of the on gastric cancer cells from the perspective of DNA total terpenoids of Celastrus orbiculatus Thunb (TTC) damage response. Methods CCK-8 experiment was conducted to investigate the toxic effects of different concentrations

Efficacy comparison of interlocking intramedullary nail and locking plate in the treatment of varus proximal humeral fractures in the elderly / 中华创伤杂志

Objective:To compare the effect of interlocking intramedullary nail and locking plate in the treatment of varus proximal humeral fractures in the elderly.Method:A retrospective case-control study was conducted to analyze the clinical data of 46 elderly patients with varus proximal humeral fractures treated in Central Theater General Hospital of PLA from June 2016 to January 2019, including 27 males and 19 females, at age of 60-84 years［（71.9±5.7）years］. All fractures were fresh. Overall 25 patients were treated with interlocking intramedullary nail（intramedullary nail group）, and 21 patients were treated with locking plate（bone plate group）. The incision length, operation time, intraoperative bleeding and fracture healing time were compared between the two groups. Visual analogue scale（VAS）was used to evaluate the degree of pain relief at 1 week and 1 month after operation, and Constant-Murley score was used to evaluate the recovery of shoulder function at 1 month, 3 months and 1 year after operation. The cervical trunk angle was recorded at 2 days and 1 year after operation to judge whether there was a loss of cervical trunk angle. Postoperative complications were observed.Results:All patients were followed up for 12-32 months［（19.7±6.6）months］. The incision length［（7.1±0.6）cm］, operation time［（60.8±5.2）minutes］, intraoperative bleeding［（64.4±8.4）ml］and fracture healing time［（10.0±1.0）weeks］in intramedullary nail group were significantly less than those in bone plate group［（13.6±0.9）cm,（80.2±8.1）minutes,（151.0±15.2）ml,（11.0±1.5）weeks］（ P<0.05）. In both groups, the VAS decreased significantly over time, and markedly increased Constant-Murley score was detected as well（ P<0.05）. The VAS in intramedullary nail group［（2.8±0.2）points,（1.1±0.2）points］was significantly lower than that in bone plate group［（4.0±0.2）points,（1.5±0.1）points］at 1 week and 1 month after operation（ P<0.05）. The Constant-Murley score in intramedullary nail group［（59.9±6.9）points,（79.1±6.8）points］was higher than that in bone plate group［（50.1±8.5）points,（73.6±8.4）points］at 1 month and 3 months after operation（ P<0.05）, but the score showed no significant difference between intramedullary nail group［（89.1±5.3）points］and bone plate group［（86.4±6.4）points］at 1 year after operation（ P>0.05）. According to Constant-Murley score, 10 patients were evaluated as excellent and 15 patients as good in intramedullary nail group at 1 year after operation, with the excellent and good rate of 100%, while 8 patients were evaluated as excellent, 11 patients as good and 2 patients as fair in bone plate group at 1 year after operation, with the excellent and good rate of 91%（ P>0.05）. The cervical trunk angle in intramedullary nail group［（140.2±2.9）°,（139.6±2.3）°］had significant difference from that in bone plate group［（139.6±3.2）°,（138.8±3.3）°］at 2 days and 1 year after operation（ P<0.05）. In both groups, the cervical trunk angle had slight lost at 1 year after operation compared with that at 2 days after operation, but the difference was not statistically significant（ P>0.05）. In intramedullary nail group, 1 patient had subacromial impact. In bone plate group, 1 patient had screw cutting, 2 patients subacromial impact, and 2 patients delayed fracture healing. The incidence of complications in intramedullary nail group was 4%（1/25）, lower than 24%（5/21）in bone plate group（ P<0.05）. Conclusion:Compared with locking nail plate, interlocking intramedullary nail in the treatment of senile varus proximal humeral fracture has the advantages of small trauma, early fracture healing, less pain, early function recovery and less complications.

Bone-strengthening effects and safety of compound peptides from skin of Chiloscyllium plagiosum and Mustelus griseus.

Fish processing produces a lot of by-products highly containing large amount of proteins which mainly consist of collagen, implying great potential value for application as nutraceutical ingredients. In present study, two kinds of sharks, Chiloscyllium plagiosum and Mustelus griseus, were used as raw material to gain three kinds of "compound peptides" (CPs) by enzymolysis, FCP (CPs from the flesh of C. plagiosum), SCP (CPs from the skin of C. plagiosum), and SMG (CPs from the skin of M. griseus). According to a series of constituent analysis, the molecule weights of FCP, SCP, and SMG were under 800 Da; amino acids composition analysis of FCP, SCP, and SMG showed that there were high glycine, proline, and hydroxyproline and low cysteine contents in SCP and SMG, which is the characteristic of collagen peptides; their total protein contents were 87.500%, 91.875%, and 95.625%, respectively; and heavy metal contents of CPs were all beneath national standards. After three kinds of CPs were administrated intragastrically to C57BL/6 mice at a total dosage of 15 g/kg, bone-strengthening effects of SCP and SMG were manifested by osteoblasts activity promotion, bone mineral density (BMD) increase, and marrow adipocyte number decrease, yet nonsignificant effects were shown in FCP group. No index showed toxicity of SCP and SMG in subacute toxicology trial, indicating their safety as functional foods. Herein, industrial application foundation of the skins from these two sharks was explored but more efforts should subsequently be implemented for further exploitation.

The inhibitory kinetics and mechanism of glycolic acid on lipase.

Obesity is prone to cause a variety of chronic metabolic diseases, and it has aroused people's attention that the rapid increase in the global population of obese people in the past years. As a kind of weight-loss drug acting in the intestine, lipase inhibitor does not enter the bloodstream without producing central nervous side effects. Because they do not affect the metabolism system, lipase inhibitors and obesity have become one of the hot spots in recent years. Glycolic acid is a new substrate analog inhibitor with the value of the semi-inhibitory concentration of lipase is estimated to be 17.29 ± 0.14 mM. Using the plots of Lineweaver-Burk, the inhibition mechanism of lipase by glycolic acid was reversible and the inhibition type belongs to competitive inhibition with a KI value of 19.61 ± 0.26 mM. The inhibitory kinetics assay showed that the microscopic velocity constant k+0 of inhibition kinetics is 1.79 × 10-3 mM-1s-1, and k-0 is 0.73 × 10-3 s-1. The results of UV full-wavelength scanning on product cumulative, fluorescence quenching and molecular simulation also indicated that glycolic acid and substrate competitive with lipase by binding to Lys137. Thereby glycolic acid inhibiting the oxidation-catalyzed reaction and reducing the product of the enzyme and substrate. This adds a new direction for the search for lipase inhibitors and provides new ideas about the development of anti-obesity drugs.Communicated by Ramaswamy H. Sarma.

Diosgenin Suppresses Cholangiocarcinoma Cells Via Inducing Cell Cycle Arrest And Mitochondria-Mediated Apoptosis.

PURPOSE: Diosgenin (DSG) is the precursor of steroid hormones and plays a crucial part in the proliferation of various carcinomas including human colorectal cancer and gastric carcinoma. Nevertheless, its specific features and mechanisms in human cholangiocarcinoma (CCA) remain unknown. METHODS: MTS assay, colony-forming assay, and EdU assay were performed to determine the role of DSG on the progression of human CCA cells. The distributions of cell cycle, the ratio of apoptosis, and the mitochondrial membrane potential (ΔΨm) were studied by flow cytometry (FCM). AO/EB and Hoechst 33258 staining were performed to observe the morphological features of cell apoptosis. TEM was performed to observe the ultrastructures of QBC939 and HuCCT1 cells. The mRNA and protein expression of mitochondrial apoptotic pathway and GSK3ß/ß-catenin pathway were further confirmed by qPCR and Western blotting. The xenograft tumor model of HuCCT1 cells was built. Immunohistochemistry of tumor tissues was performed. RESULTS: Our results indicated that DSG inhibited the progression of six CCA cell lines. In vivo tumor studies also indicated that DSG significantly inhibited tumor growth in xenografts in nude mice. The expression of mitosis-promoting factor cyclinB1 was decreased along with the elevating level of cell cycle inhibitor p21, resulting in arresting CCA cell cycles at G2/M phase. Furthermore, DSG induced apoptosis with the increased expressions of cytosol cytochrome C, cleaved-caspase-3, cleaved-PARP1 and the Bax/Bcl-2 ratio. Mechanistically, our study showed that GSK3ß/ß-catenin pathway was involved in the apoptosis of CCA cells. Thus, DSG might provide a new clue for the drug therapy of CCA. CONCLUSION: In our data, DSG was found to have efficient antitumor potential of human CCA cells in vitro and in vivo.

Progress in targeted therapy of tumor KRAS gene mutation / 中国药理学通报

Targeting KRAS mutations has always been a difficult issue in clinical tumor therapy as most tumors are accompanied by KRAS gene mutations, which indicate poor prognosis. The mutant KRAS protein is difficult to design specific inhibitors in the conventional way of inhibiting the active sites, which is known as "undmggble" target. Therefore, the exploration of drug strategies targeting KRAS mutations has become a hot spot in the research and development of antitumor drugs. Although the research progress of targeted KRAS treatment strategy is limited, some new strategies that directly or indirectly inhibit mutant KRAS are still emerging in view of the deepening understanding of KRAS mutation function and malignant mechanism. In this review, we discussed the research progress of targeted therapy for KRAS gene mutation in tumor, hoping to provide the latest clues for the treatment of KRAS mutant tumor.

Multifunctional Bacteria-Driven Microswimmers for Targeted Active Drug Delivery.

High-performance, multifunctional bacteria-driven microswimmers are introduced using an optimized design and fabrication method for targeted drug delivery applications. These microswimmers are made of mostly single Escherichia coli bacterium attached to the surface of drug-loaded polyelectrolyte multilayer (PEM) microparticles with embedded magnetic nanoparticles. The PEM drug carriers are 1 µm in diameter and are intentionally fabricated with a more viscoelastic material than the particles previously studied in the literature. The resulting stochastic microswimmers are able to swim at mean speeds of up to 22.5 µm/s. They can be guided and targeted to specific cells, because they exhibit biased and directional motion under a chemoattractant gradient and a magnetic field, respectively. Moreover, we demonstrate the microswimmers delivering doxorubicin anticancer drug molecules, encapsulated in the polyelectrolyte multilayers, to 4T1 breast cancer cells under magnetic guidance in vitro. The results reveal the feasibility of using these active multifunctional bacteria-driven microswimmers to perform targeted drug delivery with significantly enhanced drug transfer, when compared with the passive PEM microparticles.

Propulsion and Chemotaxis in Bacteria-Driven Microswimmers.

Despite the large body of experimental work recently on biohybrid microsystems, few studies have focused on theoretical modeling of such systems, which is essential to understand their underlying functioning mechanisms and hence design them optimally for a given application task. Therefore, this study focuses on developing a mathematical model to describe the 3D motion and chemotaxis of a type of widely studied biohybrid microswimmer, where spherical microbeads are driven by multiple attached bacteria. The model is developed based on the biophysical observations of the experimental system and is validated by comparing the model simulation with experimental 3D swimming trajectories and other motility characteristics, including mean squared displacement, speed, diffusivity, and turn angle. The chemotaxis modeling results of the microswimmers also agree well with the experiments, where a collective chemotactic behavior among multiple bacteria is observed. The simulation result implies that such collective chemotaxis behavior is due to a synchronized signaling pathway across the bacteria attached to the same microswimmer. Furthermore, the dependencies of the motility and chemotaxis of the microswimmers on certain system parameters, such as the chemoattractant concentration gradient, swimmer body size, and number of attached bacteria, toward an optimized design of such biohybrid system are studied. The optimized microswimmers would be used in targeted cargo, e.g., drug, imaging agent, gene, and RNA, transport and delivery inside the stagnant or low-velocity fluids of the human body as one of their potential biomedical applications.

Multi-fractal characterization of bacterial swimming dynamics: a case study on real and simulated Serratia marcescens.

To add to the current state of knowledge about bacterial swimming dynamics, in this paper, we study the fractal swimming dynamics of populations of Serratia marcescens bacteria both in vitro and in silico, while accounting for realistic conditions like volume exclusion, chemical interactions, obstacles and distribution of chemoattractant in the environment. While previous research has shown that bacterial motion is non-ergodic, we demonstrate that, besides the non-ergodicity, the bacterial swimming dynamics is multi-fractal in nature. Finally, we demonstrate that the multi-fractal characteristic of bacterial dynamics is strongly affected by bacterial density and chemoattractant concentration.

Bioadhesive Bacterial Microswimmers for Targeted Drug Delivery in the Urinary and Gastrointestinal Tracts.

Bacteria-driven biohybrid microswimmers (bacteriabots), which integrate motile bacterial cells and functional synthetic cargo parts (e.g., microparticles encapsulating drug), are recently studied for targeted drug delivery. However, adhesion of such bacteriabots to the tissues on the site of a disease (which can increase the drug delivery efficiency) is not studied yet. Here, this paper proposes an approach to attach bacteriabots to certain types of epithelial cells (expressing mannose on the membrane), based on the affinity between lectin molecules on the tip of bacterial type I pili and mannose molecules on the epithelial cells. It is shown that the bacteria can anchor their cargo particles to mannose-functionalized surfaces and mannose-expressing cells (ATCC HTB-9) using the lectin-mannose bond. The attachment mechanism is confirmed by comparing the adhesion of bacteriabots fabricated from bacterial strains with or without type I pili to mannose-covered surfaces and cells. The proposed bioadhesive motile system can be further improved by expressing more specific adhesion moieties on the membrane of the bacteria.

Chemotaxis of bio-hybrid multiple bacteria-driven microswimmers.

In this study, in a bio-hybrid microswimmer system driven by multiple Serratia marcescens bacteria, we quantify the chemotactic drift of a large number of microswimmers towards L-serine and elucidate the associated collective chemotaxis behavior by statistical analysis of over a thousand swimming trajectories of the microswimmers. The results show that the microswimmers have a strong heading preference for moving up the L-serine gradient, while their speed does not change considerably when moving up and down the gradient; therefore, the heading bias constitutes the major factor that produces the chemotactic drift. The heading direction of a microswimmer is found to be significantly more persistent when it moves up the L-serine gradient than when it travels down the gradient; this effect causes the apparent heading preference of the microswimmers and is the crucial reason that enables the seemingly cooperative chemotaxis of multiple bacteria on a microswimmer. In addition, we find that their chemotactic drift velocity increases superquadratically with their mean swimming speed, suggesting that chemotaxis of bio-hybrid microsystems can be enhanced by designing and building faster microswimmers. Such bio-hybrid microswimmers with chemotactic steering capability may find future applications in targeted drug delivery, bioengineering, and lab-on-a-chip devices.

Single-center study on transplantation of livers donated after cardiac death: A report of 6 cases.

Effective use of all available donated organs is critical, in order to meet the increasing demand for transplants. The present study explored liver transplantation with livers that were donated following cardiac death (DCD). According to the guidelines established by The Red Cross Society of China, 42 DCD organs were procured. Selected donors were treated with extracorporeal membrane oxygenation (ECMO) prior to the organ retrieval. The present single-center study included 6 liver transplantations of DCD organs (5 liver transplants and 1 liver-kidney combined transplant). All 6 recipients had a successful recovery without significant complications. The serum alanine transaminase, total bilirubin and international normalized ratio returned to the normal levels within a short period of time following transplantation, and the liver function remained normal during the follow-up period, which lasted up to 24 months. The present report demonstrated the feasibility of orthotopic liver transplantation using DCD livers. The pre-conditioning DCD donors and optimization of the recipient's condition using ECMO, played a crucial role in ensuring the success of transplantation.

Inhibitory effects of cefotaxime on the activity of mushroom tyrosinase.

Tyrosinase (EC 1.14.18.1) catalyzes both the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones that form brown or black pigments. In the present paper, cefotaxime, a cephalosporin antibacterial drug, was tested as an inhibitor of tyrosinase. The results show that cefotaxime inhibits both the monophenolase and diphenolase activities of tyrosinase. For the monophenolase activity, cefotaxime increased the lag time and decreased the steady-state activity with an IC50 of 3.2 mM. For the diphenolase activity, the inhibition by cefotaxime is reversible and mix-I type with an IC50 of 0.14 mM. The inhibition constants (K(I) and K(IS)) were determined to be 0.14 and 0.36 mM, respectively. The molecular mechanism of inhibition of tyrosinase by cefotaxime was determined by fluorescence quenching and molecular docking. The results demonstrated that cefotaxime was a static quencher of tyrosinase and that cefotaxime could dock favorably in the active site of tyrosinase. This research may offer a lead for designing and synthesizing novel and effective tyrosinase inhibitors in the future.

pH-Taxis of Biohybrid Microsystems.

The last decade has seen an increasing number of studies developing bacteria and other cell-integrated biohybrid microsystems. However, the highly stochastic motion of these microsystems severely limits their potential use. Here, we present a method that exploits the pH sensing of flagellated bacteria to realize robust drift control of multi-bacteria propelled microrobots. Under three specifically configured pH gradients, we demonstrate that the microrobots exhibit both unidirectional and bidirectional pH-tactic behaviors, which are also observed in free-swimming bacteria. From trajectory analysis, we find that the swimming direction and speed biases are two major factors that contribute to their tactic drift motion. The motion analysis of microrobots also sheds light on the propulsion dynamics of the flagellated bacteria as bioactuators. It is expected that similar driving mechanisms are shared among pH-taxis, chemotaxis, and thermotaxis. By identifying the mechanism that drives the tactic behavior of bacteria-propelled microsystems, this study opens up an avenue towards improving the control of biohybrid microsystems. Furthermore, assuming that it is possible to tune the preferred pH of bioactuators by genetic engineering, these biohybrid microsystems could potentially be applied to sense the pH gradient induced by cancerous cells in stagnant fluids inside human body and realize targeted drug delivery.