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The spread of modern humans across the globe has led to genetic adaptations to diverse local environments. Recent developments in genomic technologies, statistical analyses, and expanded sampled populations have led to improved identification and fine-mapping of genetic variants associated with adaptations to regional living conditions and dietary practices. Ongoing efforts in sequencing genomes of indigenous populations, accompanied by the growing availability of \"-omics\" and ancient DNA data, promises a new era in our understanding of recent human evolution and the origins of variable traits and disease risks.

Background Structural variants (SVs) play a crucial role in gene regulation, trait association, and disease in humans. SV genotyping has been extensively applied in genomics research and clinical diagnosis. Although a growing number of SV genotyping methods for long reads have been developed, a comprehensive performance assessment of these methods has yet to be done. Results Based on one simulated and three real SV datasets, we performed an in-depth evaluation of five SV genotyping methods, including cuteSV, LRcaller, Sniffles, SVJedi, and VaPoR. The results show that for insertions and deletions, cuteSV and LRcaller have similar F1 scores (cuteSV, insertions: 0.69–0.90, deletions: 0.77–0.90 and LRcaller, insertions: 0.67–0.87, deletions: 0.74–0.91) and are superior to other methods. For duplications, inversions, and translocations, LRcaller yields the most accurate genotyping results (0.84, 0.68, and 0.47, respectively). When genotyping SVs located in tandem repeat region or with imprecise breakpoints, cuteSV (insertions and deletions) and LRcaller (duplications, inversions, and translocations) are better than other methods. In addition, we observed a decrease in F1 scores when the SV size increased. Finally, our analyses suggest that the F1 scores of these methods reach the point of diminishing returns at 20× depth of coverage. Conclusions We present an in-depth benchmark study of long-read SV genotyping methods. Our results highlight the advantages and disadvantages of each genotyping method, which provide practical guidance for optimal application selection and prospective directions for tool improvement.

Background Periprosthetic joint infection (PJI) is a severe complication of joint arthroplasty that causes significant pain and economic loss. This study aimed to determine whether the current evidence supports single-stage revision for PJI based on reinfection and reoperation rates. Methods We searched the PubMed, EBSCO, Medline, and Cochrane Library databases from inception to 30 May 2023 to identify studies that compared single-stage revision and two-stage revision for PJI. Data on reinfection and reoperation rates were pooled. Results This meta-analysis included a total of 40 studies with 8711 patients. Overall, there was no significant difference between single- and two-stage revision regarding the postoperative reinfection rate and reoperation rate. Subgroup analysis by surgery period and different surgical sites revealed no difference between the two groups in the reinfection and reoperation rates. Conclusions Based on the available evidence, our study did not identify a significant difference in reinfection and reoperation rates between single- and two-stage revision for PJI. Given the limitations in inclusion/exclusion criteria and the observed heterogeneity, we acknowledge the complexity of drawing strong conclusions. Therefore, we suggest that the choice between single- and two-stage revision should be carefully considered on an individual basis, taking into account patient-specific factors and further research developments.

Human genomics is witnessing an ongoing paradigm shift from a single reference sequence to a pangenome form, but populations of Asian ancestry are underrepresented. Here we present data from the first phase of the Chinese Pangenome Consortium, including a collection of 116 high-quality and haplotype-phased de novo assemblies based on 58 core samples representing 36 minority Chinese ethnic groups. With an average 30.65× high-fidelity long-read sequence coverage, an average contiguity N50 of more than 35.63 megabases and an average total size of 3.01 gigabases, the CPC core assemblies add 189 million base pairs of euchromatic polymorphic sequences and 1,367 protein-coding gene duplications to GRCh38. We identified 15.9 million small variants and 78,072 structural variants, of which 5.9 million small variants and 34,223 structural variants were not reported in a recently released pangenome reference 1 . The Chinese Pangenome Consortium data demonstrate a remarkable increase in the discovery of novel and missing sequences when individuals are included from underrepresented minority ethnic groups. The missing reference sequences were enriched with archaic-derived alleles and genes that confer essential functions related to keratinization, response to ultraviolet radiation, DNA repair, immunological responses and lifespan, implying great potential for shedding new light on human evolution and recovering missing heritability in complex disease mapping. A study reports data from the first phase of the Chinese Pangenome Consortium including 116 de novo assemblies from 58 core samples representing 36 minority Chinese ethnic groups.

Bacteria and bacterial components possess multifunctional properties, making them attractive natural bio-nanocarriers for cancer diagnosis and targeted treatment. The inherent tropic and motile nature of bacteria allows them to grow and colonize in hypoxic tumor microenvironments more readily than conventional therapeutic agents and other nanomedicines. However, concerns over biosafety, limited antitumor efficiency, and unclear tumor-targeting mechanisms have restricted the clinical translation and application of natural bio-nanocarriers based on bacteria and bacterial components. Fortunately, bacterial therapies combined with engineering strategies and nanotechnology may be able to reverse a number of challenges for bacterial/bacterial component-based cancer biotherapies. Meanwhile, the combined strategies tend to enhance the versatility of bionanoplasmic nanoplatforms to improve biosafety and inhibit tumorigenesis and metastasis. This review summarizes the advantages and challenges of bacteria and bacterial components in cancer therapy, outlines combinatorial strategies for nanocarriers and bacterial/bacterial components, and discusses their clinical applications.

Background Africa is the origin of modern humans within the past 300 thousand years. To infer the complex demographic history of African populations and adaptation to diverse environments, we sequenced the genomes of 92 individuals from 44 indigenous African populations. Results Genetic structure analyses indicate that among Africans, genetic ancestry is largely partitioned by geography and language, though we observe mixed ancestry in many individuals, consistent with both short- and long-range migration events followed by admixture. Phylogenetic analysis indicates that the San genetic lineage is basal to all modern human lineages. The San and Niger-Congo, Afroasiatic, and Nilo-Saharan lineages were substantially diverged by 160 kya (thousand years ago). In contrast, the San and Central African rainforest hunter-gatherer (CRHG), Hadza hunter-gatherer, and Sandawe hunter-gatherer lineages were diverged by ~ 120–100 kya. Niger-Congo, Nilo-Saharan, and Afroasiatic lineages diverged more recently by ~ 54–16 kya. Eastern and western CRHG lineages diverged by ~ 50–31 kya, and the western CRHG lineages diverged by ~ 18–12 kya. The San and CRHG populations maintained the largest effective population size compared to other populations prior to 60 kya. Further, we observed signatures of positive selection at genes involved in muscle development, bone synthesis, reproduction, immune function, energy metabolism, and cell signaling, which may contribute to local adaptation of African populations. Conclusions We observe high levels of genomic variation between ethnically diverse Africans which is largely correlated with geography and language. Our study indicates ancient population substructure and local adaptation of Africans.

Seahorses have a specialized morphology that includes a toothless tubular mouth, a body covered with bony plates, a male brood pouch, and the absence of caudal and pelvic fins. Here we report the sequencing and de novo assembly of the genome of the tiger tail seahorse, Hippocampus comes . Comparative genomic analysis identifies higher protein and nucleotide evolutionary rates in H. comes compared with other teleost fish genomes. We identified an astacin metalloprotease gene family that has undergone expansion and is highly expressed in the male brood pouch. We also find that the H. comes genome lacks enamel matrix protein-coding proline/glutamine-rich secretory calcium-binding phosphoprotein genes, which might have led to the loss of mineralized teeth. tbx4 , a regulator of hindlimb development, is also not found in H. comes genome. Knockout of tbx4 in zebrafish showed a ‘pelvic fin-loss’ phenotype similar to that of seahorses. Here, the genome sequence of the tiger tail seahorse is reported and comparative genomic analyses with other ray-finned fishes are used to explore the genetic basis of the unique morphology and reproductive system of the seahorse. Evolution at a gallop Seahorses are prime examples of the exuberance of evolution and are unique among bony fish on several counts, including their equine body shape and male brood pouch. An international collaboration reporting in this issue of Nature has determined the genome sequence of a seahorse ( Hippocampus comes , the tiger tail seahorse). They find it to be the most rapidly evolving fish genome studied so far. H. comes is among the most commonly traded seahorse species—dried for traditional medicines and live for the aquarium trade—and is on the IUCN Red List as a 'vulnerable' species. Analysis of the genomic sequence provides insights into the evolution of its unique morphology. Of note is the absence of a master control gene, tbx4 , which functions in the development of hindlimbs and pelvic fins. Pelvic fins are missing in seahorses, and tbx4 -knockout mutant zebrafish also lack pelvic fins.

Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is a highly effective and well-tolerated antidiabetic drug. In addition to hypoglycemic effects, empagliflozin has many other effects, such as being hypotensive and cardioprotective. It also has anti-inflammatory and antioxidative stress effects in diabetic nephropathy. Several studies have shown that empagliflozin has anticancer effects. SGLT2 is expressed in a variety of cancer cell lines. The SGLT2 inhibitor empagliflozin has significant inhibitory effects on certain types of tumor cells, such as inhibition of proliferation, migration and induction of apoptosis. In conclusion, empagliflozin has promising applications in cancer therapy as a drug for the treatment of diabetes and heart failure. This article provides a brief review of the anticancer effects of empagliflozin.

Background Optimal management of Rockwood type III acromioclavicular joint (ACJ) dislocation is still debated. Our aim is to conduct a meta-analysis of clinical studies evaluating the functional outcomes of operative versus conservative treatment for Rockwood type III ACJ dislocation. Methods We conducted a systematic search across PubMed, EMBASE, Web of Science, and the Cochrane Library, including only randomized controlled trials (RCTs) focusing exclusively on type III ACJ dislocation. A total of 244 patients from four studies were included. Outcomes measured included Constant scores (CS), coracoclavicular distance (CCD), pain, and complication rates. Heterogeneity was assessed and managed to ensure robust conclusions. Results The pooled results showed no significant difference in long-term functional outcomes, measured by CS, between surgical and conservative treatments (MD: 4.82, 95% CI: -6.42 to 16.06, P  = 0.400). Surgical treatment provided better early pain relief and superior CCD at all follow-up points but did not improve long-term outcomes. Complication rates were similar for both treatments, though surgical intervention had a higher incidence of posttraumatic osteoarthritis and hardware-related issues. Conservative treatment resulted in fewer complications and comparable long-term results. Conclusions Based on the evidence, while surgical treatment may offer early benefits in pain relief and CCD improvement, it does not enhance long-term functional outcomes and is associated with higher specific complication rates. Conservative treatment provides a viable alternative with fewer complications and similar long-term outcomes. These findings highlight the need for individualized treatment plans based on patient-specific factors and suggest further high-quality, long-term studies to refine management strategies for Type III AC joint dislocations.

Background Genomic DNA reference materials are widely recognized as essential for ensuring data quality in omics research. However, relying solely on reference datasets to evaluate the accuracy of variant calling results is incomplete, as they are limited to benchmark regions. Therefore, it is important to develop DNA reference materials that enable the assessment of variant detection performance across the entire genome. Results We established a DNA reference material suite from four immortalized cell lines derived from a family of parents and monozygotic twins. Comprehensive reference datasets of 4.2 million small variants and 15,000 structural variants were integrated and certified for evaluating the reliability of germline variant calls inside the benchmark regions. Importantly, the genetic built-in-truth of the Quartet family design enables estimation of the precision of variant calls outside the benchmark regions. Using the Quartet reference materials along with study samples, batch effects are objectively monitored and alleviated by training a machine learning model with the Quartet reference datasets to remove potential artifact calls. Moreover, the matched RNA and protein reference materials and datasets from the Quartet project enables cross-omics validation of variant calls from multiomics data. Conclusions The Quartet DNA reference materials and reference datasets provide a unique resource for objectively assessing the quality of germline variant calls throughout the whole-genome regions and improving the reliability of large-scale genomic profiling.