1-[3,5-Bis(trifluoro­meth­yl)phen­yl]-3-(2-pyrid­yl)thio­urea

The title compound, C14H9F6N3S, exhibits a nearly planar conformation in the solid state, with a dihedral angle between the planes of the benzene and pyridine rings of 14.86 (3)°. The pyridine N atom allows for the formation of a six-membered N—H⋯Npy hydrogen-bonded ring, thus forcing the two amide H atoms of the thio­urea group to point in opposite directions. The second N—H group forms an inter­molecular N—H⋯S hydrogen bond with the S atom of an adjacent mol­ecule. The F atoms of the two trifluoro­methyl groups display rotational disorder around the C—CF3 axis, with an occupancy ratio of 0.54 (1):0.46 (1)

Unraveling fish diversity and assembly patterns in a temperate river: evidence from environmental DNA metabarcoding and morphological data

The loss of freshwater biodiversity has drawn greater attention to fish diversity and community assembly patterns. However, traditional survey methods, such as ground cages and electrofishing, may cause damage to fish communities and have become increasingly unsuitable for frequent and large-scale fish diversity surveys. In this study, environmental DNA (eDNA) metabarcoding and morphological data were both used to investigate the distribution and diversity of fish communities in the Taizi River basin, a temperate river in Northeast China, and the fish diversity and assembly patterns were investigated by using the null model. The results showed that a total of 7 orders, 17 families, 49 genera and 56 species were detected by the eDNA metabarcoding (6 orders, 15 families, 40 genera and 45 species) and morphological method (6 orders, 10 families, 31 genera and 34 species), and the eDNA method had a higher detection probability. Cypriniformes was detected most frequently, followed by Perciformes. Principal coordinate analysis revealed that fish communities in the Taizi River exhibited different spatial structures between the upper and lower reaches, with fish sensitive to environmental changes mostly found in the upper reaches and higher fish richness in the same area. The beta diversity in the upper reaches was higher than that in the lower reaches. The null model results showed the main factor that affected the distribution of fish in the Taizi River is the stochastic processes. Among the deterministic processes, the main environmental filter factors affecting fish community structure include total phosphorus, biochemical oxygen demand and temperature. We also confirm that eDNA metabarcoding has a higher detection rate compared to traditional survey methods, so it is feasible for freshwater ecosystem and fish resource monitoring. Therefore, the utilization of eDNA metabarcoding can effectively enhance monitoring efficiency and minimize interference with water bodies

Parkin Modulates ERRα/eNOS Signaling Pathway in Endothelial Cells

Background/Aims: Although a number of reports documented the important role of parkin in mitophagy, emerging evidence also indicated additional functions of parkin besides mitophagy. The present study was undertaken to investigate the role of parkin in the regulation of ERRα/eNOS pathway in endothelial cells (ECs). Methods: Mouse aortic endothelial cells (MAECs) and cardiac muscle HL-1 cells were transfected with parkin plasmid or siRNA. ERRα inhibitor XCT-790, autophagy inhibitor 3-MA and Bafilomycin A1, and caspase inhibitor Z-VAD-FMK were used to block autophagy or apoptosis. Western blotting was performed to examine the protein levels. Flow cytometry was applied to determine the cell apoptosis and ROS production. Mitochondrial membrane potential was measured using JC-1 and TMRM. Immunoprecipitation was performed to confirm the parkin effect on ERRα ubiquitination. Results: Overexpression of parkin resulted in a significant reduction of total-eNOS and p-eNOS in parallel with the downregulation of ERRα (a regulator of eNOS) protein and the enhancement of ERRα ubiquitination. To test the role of ERRα in regulating eNOS in this experimental setting, we treated ECs with ERRα inhibitor and found a decrement of total-eNOS and p-eNOS. On the contrary, overexpression of ERRα increased the levels of total-eNOS and p-eNOS. Meanwhile, parkin overexpression induced mitochondrial dysfunction and cell apoptosis in both ECs and HL-1 cells. Finally, we confirmed that the parkin effect on the regulation of eNOS was independent of the autophagy and apoptosis. Conclusion: These findings suggested that parkin overexpression downregulated eNOS possibly through the ubiquitination of ERRα in endothelial cells

Frozen inactivated autograft replantation for bone and soft tissue sarcomas

BackgroundThe frozen inactivation of autologous tumor bones using liquid nitrogen is an important surgical method for limb salvage in patients with sarcoma. At present, there are few research reports related to frozen inactivated autograft replantation.MethodsIn this study, we retrospectively collected the clinical data of patients with bone and soft tissue sarcoma treated with liquid nitrogen-frozen inactivated tumor bone replantation, and analyzed the safety and efficacy of this surgical method. The healing status of the frozen inactivated autografts was evaluated using the International Society of Limb Salvage (ISOLS) scoring system. Functional status of patients was assessed using the Musculoskeletal Tumor Society (MSTS) scale.ResultsThis study included 43 patients. The average length of the bone defect after tumor resection is 16.9 cm (range 6.3–35.3 cm). Patients with autograft not including the knee joint surface had significantly better healing outcomes (ISOLS scores) (80.6% ± 15% vs 28.2% ± 4.9%, P<0.001) and limb function (MSTS score) (87% ± 11.6% vs 27.2% ± 4.4%, P<0.001) than patients with autografts including the knee joint surface. The healing time of the end of inactivated autografts near the metaphyseal was significantly shorter than that of the end far away from the metaphyseal (9.8 ± 6.3 months vs 14.9 ± 6.3 months, P=0.0149). One patient had local recurrence, one had an autograft infection, five (all of whom had an autograft including the knee joint surface) had joint deformities, and seven had bone non-union.ConclusionFrozen inactivated autologous tumor bone replantation is safe and results in good bone healing. But this method is not suitable for patients with autograft involving the knee joint surface

Investigating Dynamic Molecular Events in Melanoma Cell Nucleus During Photodynamic Therapy by SERS

Photodynamic therapy (PDT) involves the uptake of photosensitizers by cancer cells and the irradiation of a light with a specific wavelength to trigger a series of photochemical reactions based on the generation of reactive oxygen, leading to cancer cell death. PDT has been widely used in various fields of biomedicine. However, the molecular events of the cancer cell nucleus during the PDT process are still unclear. In this work, a nuclear-targeted gold nanorod Raman nanoprobe combined with surface-enhanced Raman scattering spectroscopy (SERS) was exploited to investigate the dynamic intranuclear molecular changes of B16 cells (a murine melanoma cell line) treated with a photosensitizer (Chlorin e6) and the specific light (650 nm). The SERS spectra of the cell nucleus during the PDT treatment were recorded in situ and the spectroscopic analysis of the dynamics of the nucleus uncovered two main events in the therapeutic process: the protein degradation and the DNA fragmentation. We expect that these findings are of vital significance in having a better understanding of the PDT mechanism acting on the cancer cell nucleus and can further help us to design and develop more effective therapeutic platforms and methods

Caveolin-1 Plays a Crucial Role in Inhibiting Neuronal Differentiation of Neural Stem/Progenitor Cells via VEGF Signaling-Dependent Pathway

In the present study, we aim to elucidate the roles of caveolin-1(Cav-1), a 22 kDa protein in plasma membrane invaginations, in modulating neuronal differentiation of neural progenitor cells (NPCs). In the hippocampal dentate gyrus, we found that Cav-1 knockout mice revealed remarkably higher levels of vascular endothelial growth factor (VEGF) and the more abundant formation of newborn neurons than wild type mice. We then studied the potential mechanisms of Cav-1 in modulating VEGF signaling and neuronal differentiation in isolated cultured NPCs under normoxic and hypoxic conditions. Hypoxic embryonic rat NPCs were exposed to 1% O2 for 24 h and then switched to 21% O2 for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O2. Compared with normoxic NPCs, hypoxic NPCs had down-regulated expression of Cav-1 and up-regulated VEGF expression and p44/42MAPK phosphorylation, and enhanced neuronal differentiation. We further studied the roles of Cav-1 in inhibiting neuronal differentiation by using Cav-1 scaffolding domain peptide and Cav-1-specific small interfering RNA. In both normoxic and hypoxic NPCs, Cav-1 peptide markedly down-regulated the expressions of VEGF and flk1, decreased the phosphorylations of p44/42MAPK, Akt and Stat3, and inhibited neuronal differentiation, whereas the knockdown of Cav-1 promoted the expression of VEGF, phosphorylations of p44/42MAPK, Akt and Stat3, and stimulated neuronal differentiation. Moreover, the enhanced phosphorylations of p44/42MAPK, Akt and Stat3, and neuronal differentiation were abolished by co-treatment of VEGF inhibitor V1. These results provide strong evidence to prove that Cav-1 can inhibit neuronal differentiation via down-regulations of VEGF, p44/42MAPK, Akt and Stat3 signaling pathways, and that VEGF signaling is a crucial target of Cav-1. The hypoxia-induced down-regulation of Cav-1 contributes to enhanced neuronal differentiation in NPCs

The Relationship Between Cognitive Dysfunction and Symptom Dimensions Across Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Background: Cognitive dysfunction is considered a core feature among schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Despite abundant literature comparing cognitive dysfunction among these disorders, the relationship between cognitive dysfunction and symptom dimensions remains unclear. The study aims are a) to identify the factor structure of the BPRS-18 and b) to examine the relationship between symptom domains and cognitive function across SZ, BD, and MDD.Methods: A total of 716 participants [262 with SZ, 104 with BD, 101 with MDD, and 249 healthy controls (HC)] were included in the study. One hundred eighty participants (59 with SZ, 23 with BD, 24 with MDD, and 74 HC) completed the MATRICS Consensus Cognitive Battery (MCCB), and 507 participants (85 with SZ, 89 with BD, 90 with MDD, and 243 HC) completed the Wisconsin Card Sorting Test (WCST). All patients completed the Brief Psychiatric Rating Scale (BPRS).Results: We identified five BPRS exploratory factor analysis (EFA) factors (“affective symptoms,” “psychosis,” “negative/disorganized symptoms,” “activation,” and “noncooperation”) and found cognitive dysfunction in all of the participant groups with psychiatric disorders. Negative/disorganized symptoms were the most strongly associated with cognitive dysfunctions across SZ, BD, and MDD.Conclusions: Our findings suggest that cognitive dysfunction severity relates to the negative/disorganized symptom domain across SZ, BD, and MDD, and negative/disorganized symptoms may be an important target for effective cognitive remediation in SZ, BD, and MDD

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead