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Abstract Autophagosomes are double-membrane vesicles generated intracellularly to encapsulate substrates for lysosomal degradation during autophagy. Phase separated p62 body plays pivotal roles during autophagosome formation, however, the underlying mechanisms are still not fully understood. Here we describe a spatial membrane gathering mode by which p62 body functions in autophagosome formation. Mass spectrometry-based proteomics reveals significant enrichment of vesicle trafficking components within p62 body. Combining cellular experiments and biochemical reconstitution assays, we confirm the gathering of ATG9 and ATG16L1-positive vesicles around p62 body, especially in Atg2ab DKO cells with blocked lipid transfer and vesicle fusion. Interestingly, p62 body also regulates ATG9 and ATG16L vesicle trafficking flux intracellularly. We further determine the lipid contents associated with p62 body via lipidomic profiling. Moreover, with in vitro kinase assay, we uncover the functions of p62 body as a platform to assemble ULK1 complex and invigorate PI3KC3-C1 kinase cascade for PI3P generation. Collectively, our study raises a membrane-based working model for multifaceted p62 body in controlling autophagosome biogenesis, and highlights the interplay between membraneless condensates and membrane vesicles in regulating cellular functions.

Objective: To investigate 38 Y-chromosome short tandem repeat (Y-STR) genetic polymorphisms in Beijing Han and analyze the genetic distance with neighboring or linguistically similar populations. Materials and Methods: In the study, we selected 531 unrelated male individuals of Beijing Han, and the results were statistically analyzed by testing with GSTAR™ 41Y reagents. Results: The allele peak heights were balanced among the Y loci, the amplified fragment ranged from 100 to 500 bps. A total of 531 haplotypes were detected in 531 samples. Eight null genotypes were observed on locus DYS448. One and three double alleles were observed on single-copy locus DYS576 and DYS19, respectively. DYS385 a/b, DYF387S1 a/b, and DYS527 a/b were more common in double copies, but 3, 13, and 11 triple alleles were detected, respectively. The gene diversity values of Y-STRs except DYS391, DYS438, and DYS645 were >0.5. Twenty-seven Y-STRs of Beijing Han population were selected for genetic distance comparison with 17 populations including Changchun Han, with Rst values ranging from 0.0002 to 0.1703. Conclusion: The 38 Y-STRs in this study have strong male lineage identification ability and have great potential for individual identification, kinship identification, Y-STR database construction, and genetic relationship research.

To investigate the genetic polymorphisms of 19 X-STR loci in the Han population in Northern China, samples from 628 unrelated individuals (314 males and 314 females) were collected and 19 X-STR loci were amplified by AGCU X19 STR System. A total of 270 different alleles were detected in 19 X-STR loci. All loci were in Hardy − Weinberg equilibrium and there was only one pair of linkage loci (DXS10103-DXS10101). There was no significant difference in allele frequency between male and female populations. The combined power of discrimination in males was 1–1.8667 × 10−13, while the combined power of discrimination in females was 1–3.6532 × 10−22. The combined mean paternity exclusion chance (CMEC) for X-chromosomal markers in father/daughter or mother/son duos Mean paternity exclusion chance (MECDesmarais Duo) was 1–5.1109 × 10−9. Moreover, the CMEC for X-chromosomal markers in trios involving daughters (MECDesmarais) was 1–2.0292 × 10−12. The compound amplification system composed of 19 X-STR in this study showed high polymorphism in the Han population of Northern China, which had a high application value in difficult genetic relationship identification.

This study aimed to investigate the application of autosomal short tandem repeat (STR) loci using the ITO method and discriminant function algorithm for full-sibling (FS) identification. A total of 342 pairs of full siblings (FSs) and 3900 pairs of unrelated individuals (UIs) were genotyped at 51 STR loci. The groups were in accordance with discrimination power (DP) values and the number of loci, and the values of FS index (FSI) of FSs and UIs were calculated by the ITO method. The discriminant functions of FS–UI were established using the Fisher's discriminant analysis method with SPSS 19.0 software. All the lgFSI values in the FS and UI groups followed a normal distribution, and there were significant differences between the two pairs. A higher average DP value was associated with a more significant difference, as was a greater number of STR loci detected. Receiver operator characteristic curves showed that the accuracy of FS identification can be affected by both locus polymorphism and the number of loci detected. Comparing the rate of false positives and false negatives of discriminant function between the two groups, a higher average DP value and larger number of loci detected were associated with a lower rate of miscarriage of justice and were more helpful for FS–UI identification. The ITO-based discriminant analysis method has high applicability in FS–UI tests. Testing of a greater number of STR loci promotes FS identification.

The CXC chemokines belong to a family which includes 17 different CXC members. Accumulating evidence suggests that CXC chemokines regulate tumor cell proliferation, invasion, and metastasis in various types of cancers by influencing the tumor microenvironment. The different expression profiles and specific function of each CXC chemokine in head and neck squamous cell carcinoma (HNSCC) are not yet clarified. In our work, we analyzed the altered expression, interaction network, and clinical data of CXC chemokines in patients with HNSCC by using the following: the Oncomine dataset, cBioPortal, Metascape, String analysis, GEPIA, and the Kaplan–Meier plotter. The transcriptional level analysis suggested that the mRNA levels of CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, CXCL9, CXCL10, CXCL11, and CXCL13 increased in HNSCC tissue samples when compared to the control tissue samples. The expression levels of CXCL9, CXCL10, CXCL11, CXCL12, and CXCL14 were associated with various tumor stages in HNSCC. Clinical data analysis showed that high transcription levels of CXCL2, CXCL3, and CXCL12, were linked with low relapse-free survival (RFS) in HNSCC patients. On the other hand, high CXCL14 levels predicted high RFS outcomes in HNSCC patients. Meanwhile, increased gene transcription levels of CXCL9, CXCL10, CXCL13, CXCL14, and CXCL17 were associated with a higher overall survival (OS) advantage in HNSCC patients, while high levels of CXCL1, and CXCL8 were associated with poor OS in all HNSCC patients. This study implied that CXCL1, CXCL2, CXCL3, CXCL8, and CXCL12 could be used as prognosis markers to identify low survival rate subgroups of patients with HNSCC as well as be potential suitable therapeutic targets for HNSCC patients. Additionally, CXCL9, CXCL10, CXCL13, CXCL14, and CXCL17 could be used as functional prognosis biomarkers to identify better survival rate subgroups of patients with HNSCC.

Complex kinship identification such as half-sibling identification is a difficult task in forensic biology Here we represented an approach in dealing with half-sisters from different mothers, with the combination of autosomal and X chromosomal short-tandem repeats (STRs) data. X chromosomal STRs can offer additional information, especially in some cases where autosomal STRs alone may not provide enough information for an accurate opinion. In this case, half-sister or unrelated relationship between two women (S1 and S2) with different mothers were distinguished. 23 autosomal and 31 X chromosomal STRs of S1, S2, S1's mother (M1), S2's mother (M2) and S1's grandmother (G1) were profiled with three different commercial kits. As to X-chromosome STRs, likelihood ratios (LRs) were calculated by FamLinkX with consideration of linkage, linkage disequilibrium, and mutations. When only the profiles of the two individuals (S1 and S2) were available, LRs between S1 and S2 were 1.1110 × 10² based on 23 autosomal STRs and 3.2257 om107 based on 31 X chromosomal STRs. When the maternal genotypes were taken into consideration, LRs increased to 2.5297 × 10³ and 3.0563 × 1018. Therefore, both the DNA profiles of each mothers and X chromosomal STRs are important in dealing with the identification of half-sisters from different mothers. [ABSTRACT FROM AUTHOR]

Background: The 3D structure and functions of ENPP4, a protein expressed on the surface of Bacillus Calmette--Guerin (BCG)-activated macrophages, are unknown. In this study, we analyzed the 3D structure of ENPP4 and determined its tumoricidal effects on MCA207 cells. Results: Homology modeling showed that Arg305, Tyr341, Asn291, and Asn295 are important residues in substrate, adenosine triphosphate (ATP), binding. A molecular dynamics study was also carried out to study the stability of ENPP4 (including zinc atoms) as well as its ligand--enzyme complex. BCG increased ENPP4 expression in macrophages, and specific blocking of ENPP4 in BCG-activated macrophages (BAMs) significantly reduced their cytotoxicity against MCA207 cells. Conclusions: These results indicate that zinc remains inside the ENPP4 protein, a BCG activated tumoricidal macrophage protein, throughout the simulation. Important information for the design of new inhibitors was obtained. [ABSTRACT FROM AUTHOR]