Study on the geographic distribution and influencing factors of Dai settlements in Yunnan based on geodetector.

The Dai people are primarily found in Yunnan Province, China, and have a long heritage there. The latest national census reports that Yunnan is home to 1,259,000 individuals of the Dai ethnic group. This study focuses on 3504 Dai settlements in Yunnan, identified through county records. Using the ArcGIS spatial analysis platform, we first evaluated their settlements' spatial distribution patterns using metrics like the nearest neighbor index and geographic concentration index. Then, we applied geodetector to investigate the underlying mechanisms of their distribution. The results reveal that: (1) Dai settlements in Yunnan Province generally have a cohesive spatial distribution; at the provincial level, however, there is an uneven distribution pattern, with many densely populated areas and a pattern of "two cores, one belt, one area, and two points"; (2) The Dai settlements predominantly occupy the third gradient of the vertical zonation, with Dai gathering settlements primarily found in the Lancang, Ayeyarwaddy, and Red River basins. Conversely, Dai mixed settlements are mainly situated in the Lancang, Red, and Nu River basins; (3) Analysis via geodetector indicates that ethnocultural factors are the most significant in determining the spatial distribution of the Dai settlements, followed by socio-economic and natural factors; (4) The distribution of settlements is significantly influenced by the proportion of the Dai population within these settlements. Dai gathering settlements are typically located on flat slopes with elevations ranging from 500 to 1000 m and slopes of 0°-5°. Meanwhile, Dai mixed settlements are found on gentle slopes with elevations of 1000-2000 m and slopes of 5°-15°. The study reveals that the location of Dai settlements is strongly influenced by environmental considerations and has a significant explanation from similar origins.

Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes.

Curcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs), and cytochrome P450 (CYP) enzymes (CYP3A4, 1A2, 2E1, and 2C19) in an NADPH-generating system in vitro were evaluated by UP-HPLC-MS/MS (ultrahigh-pressure liquid chromatography-tandem mass spectrometry). The contents of four cytochrome P450 (CYP) enzymes, adjusting by the compounds were detected using Western blotting in vitro and in vivo. The t1/2 of curcumin was 22.35 min in RLMs and 173.28 min in HLMs, while 18.02 and 16.37 min were gained for germacrone. The Vmax of curcumin in RLMs was about 4-fold in HLMs, meanwhile, the Vmax of germacrone in RLMs was similar to that of HLMs. The single enzyme t1/2 of curcumin was 38.51 min in CYP3A4, 301.4 min in 1A2, 69.31 min in 2E1, 63.01 min in 2C19; besides, as to the same enzymes, t1/2 of germacrone was 36.48 min, 86.64 min, 69.31 min, and 57.76 min. The dynamic curves were obtained by reasonable experimental design and the metabolism of curcumin and germacrone were selected in RLMs/HLMs. The selectivities in the two liver microsomes differed in degradation performance. These results meant that we should pay more attention to drugs in clinical medication-drug and drug-enzyme interactions.

Differential MC5R loss in whales and manatees reveals convergent evolution to the marine environment.

Melanocortin 5 receptor (MC5R), which is expressed in the terminally differentiated sebaceous gland, is a G protein-coupled receptor (GPCR). MC5R exists mostly in mammals but is completely lost in whales; only the relic of MC5R can be detected in manatees, and phenotypically, they have lost sebaceous glands. Interestingly, whales and manatees are both aquatic mammals but have no immediate common ancestors. The loss of MC5R and sebaceous glands in whales and manatees is likely to be a result of convergent evolution. Here, we find that MC5R in whales and manatees are lost by two different mechanisms. Homologous recombination of MC5R in manatees and the insertion of reverse transcriptase in whales lead to the gene loss, respectively. On one hand, in manatees, there are two "TTATC" sequences flanking MC5R, and homologous recombination of the segments between the two "TTATC" sequences resulted in the partial loss of the sequence of MC5R. On the other hand, in whales, reverse transcriptase inserts between MC2R and RNMT on the chromosome led to the loss of MC5R. Based on these two different mechanisms for gene loss in whales and manatees, we finally concluded that MC5R loss might be the result of convergent evolution to the marine environment, and we explored the impact on biological function that is significant to environmental adaptation.

KSHV-encoded ORF45 activates human NLRP1 inflammasome.

At steady state, the NOD-like receptor (NLR)-containing pyrin domain (PYD) (NLRP)1 inflammasome is maintained in an auto-inhibitory complex by dipeptidyl peptidases 8 and 9 (DPP8 and DPP9) and is activated by pathogen-encoded proteases after infection. Here, we showed that the open reading frame (ORF)45 protein of the Kaposi's sarcoma-associated herpesvirus activated the human NLRP1 (hNLRP1) inflammasome in a non-protease-dependent manner, and we additionally showed that the Linker1 region of hNLRP1, situated between the PYD and NACHT domains, was required for the auto-inhibition and non-protease-dependent activation of hNLRP1. At steady state, the interaction between Linker1 and the UPA subdomain silenced the activation of hNLRP1 in auto-inhibitory complexes either containing DPP9 or not in a manner independent of DPP9. ORF45 binding to Linker1 displaced UPA from the Linker1-UPA complex and induced the release of the C-terminal domain of hNLRP1 for inflammasome assembly. The ORF45-dependent activation of the NLRP1 inflammasome was conserved in primates but was not observed for murine NLRP1b inflammasomes.

RSK1 SUMOylation is required for KSHV lytic replication.

RSK1, a downstream kinase of the MAPK pathway, has been shown to regulate multiple cellular processes and is essential for lytic replication of a variety of viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV). Besides phosphorylation, it is not known whether other post-translational modifications play an important role in regulating RSK1 function. We demonstrate that RSK1 undergoes robust SUMOylation during KSHV lytic replication at lysine residues K110, K335, and K421. SUMO modification does not alter RSK1 activation and kinase activity upon KSHV ORF45 co-expression, but affects RSK1 downstream substrate phosphorylation. Compared to wild-type RSK1, the overall phosphorylation level of RxRxxS*/T* motif is significantly declined in RSK1K110/335/421R expressing cells. Specifically, SUMOylation deficient RSK1 cannot efficiently phosphorylate eIF4B. Sequence analysis showed that eIF4B has one SUMO-interacting motif (SIM) between the amino acid position 166 and 170 (166IRVDV170), which mediates the association between eIF4B and RSK1 through SUMO-SIM interaction. These results indicate that SUMOylation regulates the phosphorylation of RSK1 downstream substrates, which is required for efficient KSHV lytic replication.

A fast and effective detection framework for whole-slide histopathology image analysis.

Pathologists generally pan, focus, zoom and scan tissue biopsies either under microscopes or on digital images for diagnosis. With the rapid development of whole-slide digital scanners for histopathology, computer-assisted digital pathology image analysis has attracted increasing clinical attention. Thus, the working style of pathologists is also beginning to change. Computer-assisted image analysis systems have been developed to help pathologists perform basic examinations. This paper presents a novel lightweight detection framework for automatic tumor detection in whole-slide histopathology images. We develop the Double Magnification Combination (DMC) classifier, which is a modified DenseNet-40 to make patch-level predictions with only 0.3 million parameters. To improve the detection performance of multiple instances, we propose an improved adaptive sampling method with superpixel segmentation and introduce a new heuristic factor, local sampling density, as the convergence condition of iterations. In postprocessing, we use a CNN model with 4 convolutional layers to regulate the patch-level predictions based on the predictions of adjacent sampling points and use linear interpolation to generate a tumor probability heatmap. The entire framework was trained and validated using the dataset from the Camelyon16 Grand Challenge and Hubei Cancer Hospital. In our experiments, the average AUC was 0.95 in the test set for pixel-level detection.

(2,2'-Bipyridine-κN,N')bis-(3-meth-oxy-benzoato-κO,O)copper(II) mono-hydrate.

The title compound, [Cu(C(8)H(7)O(3))(2)(C(10)H(8)N(2))]·H(2)O, is comprised of a Cu(II) ion, two 3-meth-oxy-benzoate ligands, a 2,2'-bipyridine (bipy) ligand and one uncoordinated water mol-ecule. The Cu(II) ion and the water O atom lie on a twofold axis. The Cu(II) ion exhibits a six-coordinate distorted octa-hedral geometry, with two N atoms from the bipy ligand [Cu-N = 1.9996 (16) Å] and four O atoms from two 3-meth-oxy-benzoate ligands [Cu-O = 1.9551 (15) and 2.6016 (16) Å]. The mol-ecules are linked by O-H⋯O and C-H⋯O hydrogen bonds, forming a three-dimensional network.