Influence of continuous renal replacement therapy on the plasma concentration of tigecycline in patients with septic shock: A prospective observational study.

Objective: The influence of continuous renal replacement therapy (CRRT) on the steady-state plasma concentration of high-dose tigecycline was investigated in septic shock patients to provide references for drug dosing. Methods: In this prospective observational study, 17 septic shock patients presenting with severe infections needing a broad-spectrum antibiotic therapy with high-dose tigecycline (100 mg per 12 h) in the intensive care unit were included and divided into CRRT group (n = 6) or non-CRRT group (n = 11). The blood samples were collected and plasma drug concentration was determined by SHIMADZU LC-20A and SHIMADZU LCMS 8040. The steady-state plasma concentration was compared between groups using unpaired t-test. Furthermore, between-groups comparisons adjusted for baseline value was also done using multivariate linear regression model. Results: Peak concentration (Cmax) of tigecycline was increased in CRRT group compared to non-CRRT group, but there were no statistical differences (505.11 ± 143.84 vs. 406.29 ± 108.00 ng/mL, p-value: 0.129). Trough concentration (Cmin) of tigecycline was significantly higher in CRRT group than in non-CRRT group, with statistical differences (287.92 ± 41.91 vs. 174.79 ± 33.15 ng/mL, p-value: 0.000, adjusted p-value: 0.000). In safety, Cmin was reported to be a useful predictor of hepatotoxicity with a cut-off of 474.8 ng/mL. In our studies, Cmin of all patients in CRRT group was lower than 474.8 ng/mL. Conclusion: The plasma concentration of tigecycline was increased in septic shock patients with CRRT treatment and only Cmin shown statistical differences. No dose adjustment seems needed in the view of hepatotoxicity. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2000037475.

Establishment of a patient-derived organoid model and living biobank for nasopharyngeal carcinoma.

Background: Recurrent nasopharyngeal carcinoma (NPC) remains a major challenge for clinicians and scientists. Tumor organoid is a revelational disease model that highly resembled the heterogeneity and histopathological characteristics of original tumors. This study aimed to optimize the modeling process of patient-derived NPC organoids (NPCOs), and establish a living-biobank of NPCs to study the mechanism and explore the more effective treatment of the disease. Methods: Sixty-two fresh NPC tissue samples and 15 normal mucosa samples were collected for 3-dimensional (3D) organoid culture. The organoids were confirmed using hematoxylin and eosin assays. The expression levels of CD133, CD44, BMI-1, and Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) were detected by immunohistochemistry (IHC) and in situ hybridization (ISH). Recurrent NPCOs were frozen in liquid nitrogen for 6 months and then resuscitated and passaged. Results: We identified a novel two-step enzymatic strategy for the treatment of NPC and nasal mucosa specimens and an optimal medium for culturing NPCOs and nasal mucosa organoids (NMOs). Organoid cultures were generated from 34 primary NPC samples, 28 recurrent NPC samples, and 15 normal mucosa samples. The success rates for primary NPCO, recurrent NPCO, and NMO formation were 47.06%, 81.25%, and 86.5%, respectively. All the NPCOs were EBER positive and CK7 negative. Recurrent NPCOs had higher expressions of stem cell markers, including BMI-1, CD44, and CD133. Additionally, recurrent NPCOs could be cultured to passage 4 and frozen and revived repeatedly, while primary NPCOs were challenging to culture. Conclusions: In summary, we successfully established a living biobank using the NPCO model, which has enormous potential in basic and clinical research on NPC.

Nanosensitizers for sonodynamic therapy for glioblastoma multiforme: current progress and future perspectives.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood-brain barrier (BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy (SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.

Optimization of Heat Treatment for 38Si7 Spring Steel with Excellent Mechanical Properties and Controlled Decarburization.

Optimizing the heat treatment procedure with 13 mm diameter 38Si7 spring steel is critical for developing high-performance, low-cost, large spring steel for railway clips. The effects of quenching temperature, holding time, tempering temperature, and tempering time on the microstructure and mechanical properties were investigated using an orthogonal experiment, designed with four factors and three levels. The best heat treatment settings were explored, as well as the variation laws of mechanical properties, decarburization behavior, and fracture morphology. The results demonstrated that quenching temperature and tempering temperature had the most impact on plasticity and tempering temperature, while time had the most effect on strength. The optimized heat treatment schemes made the elongation increase by up to 106% and the reduction in area increase by up to 67%, compared with the standard BS EN 10089-2002, and there were mixed fractures caused by ductility and brittleness. The fracture tests showed a good performance of 20.2 GPa·%, and the heat treatment processes' minimum decarburization depth of 93.4 µm was determined. The optimized process would obtain stronger plastic deposition and better decarburization performance. The microstructure was simply lightly tempered martensite, and the matrix still retained the acicular martensite. The optimal heat treatment process is quenching at 900 °C for 30 min (water cooling), followed by tempering at 430 °C for 60 min (air cooling). The research led to a solution for increasing the overall mechanical characteristics and decreasing the surface decarburization of 38Si7 spring steel with a diameter of 13 mm, and it set the foundation for increasing the mass production of railway clips of this size.

Heterogeneous public preferences for controlling agricultural non-point source pollution based on a choice experiment.

The public's stated value and heterogeneous preferences are crucial for formulating policies and financing approaches to promote the control of agricultural non-point-source pollution (ANSP). This study aims to investigate urban residents' willingness to pay (WTP) for ANSP control and analyse the source of preference heterogeneity using a choice experiment method. Survey data were obtained from face-to-face interviews with 595 respondents in south Shaanxi Province, China. We found that respondents' average WTP for the attributes of ANSP control schemes were 2.34 yuan ($0.36) and 5.42 yuan ($0.83) per year per household for a 1% reduction in fertiliser and pesticide use, respectively. We also found significant impacts of WTP from individuals' socio-economic characteristics (i.e., gender, age, education, and income) and cognitive factors (i.e., policy understanding, and government trust). Thus, to improve the efficiency and universality of ANSP control policy, the public's willingness and preference heterogeneity should be thoroughly taken into policy formulation.

[DNA Extraction of Cast-off Cells of Fingerprints from 502 Glue Fumigated Contact Samples].

OBJECTIVE: To establish a method of fingerprint position, sample transfer and fingerprint DNA extraction in contact samples. METHODS: Sixty-six cases were visualized by 502 glue fingerprint fumigation. Two methods, ordinary wipe and acetone wipe, were used to transfer cast-off cells of fingerprints from testing samples, respectively. DNA was extracted and purified by ultramicro magnetic bead kit. The data was resolved on genetic analysis after amplification. RESULTS: In 33 samples, 30 samples got better STR analysis by acetone wipe method. The peak range was 1,000-4,000 RFU and peak shapes were equable. It was hard to get ideal STR typing by ordinary wipe method. CONCLUSION: The samples are visualized by 502 glue fingerprint fumigation and the case-off cells are transferred by acetone wipe method. The method shows better STR analysis result, which might be a better method for forensic science practice.

Effects of cadmium on absorption, excretion, and distribution of nickel in rats.

The effects of cadmium (Cd (II)) on absorption, excretion, and distribution of nickel (Ni (II)) were studied in rats using (63)Ni-NiCl(2) as radiotracer in the presence and absence of CdCl(2), through intraperitoneal injection (i.p.). The time-concentration curves in the blood were fitted with a two-compartment model. The peak time (t ((peak))) is 0.31 h in the absence of Cd (II), and it is 5.5 h in the presence of Cd (II). The levels of nickels were higher at 3 h and lower (close to zero) at 24 h in all organs of interest, except kidneys, in the absence of Cd (II). There still residue Ni (II) at 72 h post-injection in the presence of Cd (II). The Cd (II) did effect the total Ni (II) excretion 24 h post-injection. Our study showed that cadmium has a competitive effect on the absorption of nickel and an inhibitory effect on the elimination of it, so cadmium may induce the bioaccumulation of nickel in the body.

A family of new glutarate compounds: synthesis, crystal structures of: Co(H2O)5L(1), Na2[CoL2] (2), Na2[L(H2L)4/2] (3), {[Co3(H2O)6L2](HL)2}.4H2O (4), {[Co3(H2O)6L2](HL)2}.10H2O (5), {[Co3(H2O)6L2]L2/2}.4H2O (6), and Na2{[Co3(H2O)2]L8/2].6H2O (7), and magnetic properties of 1 and 2 with H2L = HOOC-(CH2)3-COOH.

Seven new glutaric acid complexes, Co(H 2O) 5L 1, Na 2[CoL 2] 2, Na 2[L(H 2L) 4/2] 3, {[Co 3(H 2O) 6L 2](HL) 2}.4H 2O 4, {[Co 3(H 2O) 6L 2](HL) 2}.10H 2O 5, {[Co 3(H 2O) 6L 2]L 2/2}.4H 2O 6, and Na 2{[Co 3(H 2O) 2]L 8/2].6H 2O 7 were obtained and characterized by single-crystal X-ray diffraction methods along with elemental analyses, IR spectroscopic and magnetic measurements (for 1 and 2). The [Co(H 2O) 5L] complex molecules in 1 are assembled into a three-dimensional supramolecular architecture based on intermolecular hydrogen bonds. Compound 2 consists of the Na (+) cations and the necklace-like glutarato doubly bridged [ C o L 4 / 2 ] 2 - infinity 1 anionic chains, and 3 is composed of the Na (+) cations and the anionic hydrogen bonded ladder-like [ L ( H 2 L ) 4 / 2 ] 2 - infinity 1 anionic chains. The trinuclear {[Co 3(H 2O) 6L 2](HL) 2} complex molecules with edge-shared linear trioctahedral [Co 3(H 2O) 6L 2] (2+) cluster cores in 4 and 5 are hydrogen bonded into two-dimensional (2D) networks. The edge-shared linear trioctahedral [Co 3(H 2O) 6L 2] (2+) cluster cores in 6 are bridged by glutarato ligands to generate one-dimensional (1D) chains, which are then assembled via interchain hydrogen bonds into 2D supramolecular networks. The corner-shared linear [Co 3O 16] trioctahedra in 7 are quaternate bridged by glutarato ligands to form 1D band-like anionic {[Co 3(H 2O) 2]L 8/2} (2+) chains, which are assembled via interchain hydrogen bonds into 2D layers, and between them are sandwiched the Na (+) cations. The magnetic behaviors of 1 and 2 obey the Curie-Weiss law with chi m = C/( T - Theta) with the Curie constant C = 3.012(8) cm (3) x mol (-1) x K and the Weiss constant Theta = -9.4(7) K for 1, as well as C = 2.40(1) cm (3) x mol (-1) x K and Theta = -2.10(5) K for 2, indicating weak antiferromagnetic interactions between the Co(II) ions.

A novel mixed-valence copper complex, poly[[mu2-4,4'-bipyridine-mu3-pyridine-2,4,6-tricarboxylato-dicopper(I,II)] monohydrate].

In the title novel mixed-valence copper complex, {[Cu2(C8H2NO6)(C10H8N2)].H2O}n, the Cu(I) and Cu(II) ions are linked by 4,4'-bipyridine (bpy) and pyridine-2,4,6-tricarboxylate (ptc) ligands into corrugated layers, which are assembled via interlayer C-H...O hydrogen bonds to give a three-dimensional supramolecular architecture.