Evaluating three strategies of genome-wide association analysis for integrating data from multiple populations.

In livestock, genome-wide association studies (GWAS) are usually conducted in a single population (single-GWAS) with limited sample size and detection power. To enhance the detection power of GWAS, meta-analysis of GWAS (meta-GWAS) and mega-analysis of GWAS (mega-GWAS) have been proposed to integrate data from multiple populations at the level of summary statistics or individual data, respectively. However, there is a lack of comparison for these different strategies, which makes it difficult to guide the best practice of GWAS integrating data from multiple study populations. To maximize the comparison of different association analysis strategies across multiple populations, we conducted single-GWAS, meta-GWAS, and mega-GWAS for the backfat thickness of 100 kg (BFT_100) and days to 100 kg (DAYS_100) within each of the three commercial pig breeds (Duroc, Yorkshire, and Landrace). Based on controlling the genome inflation factor to one, we calculated corrected p-values (pC ). In Yorkshire, with the largest sample size, mega-GWAS, meta-GWAS and single-GWAS detected 149, 38 and 20 significant SNPs (pC < 1E-5) associated with BFT_100, as well as 26, four, and one QTL, respectively. Among them, pC of SNPs from mega-GWAS was the lowest, followed by meta-GWAS and single-GWAS. The correlation of pC among the three GWAS strategies ranged from 0.60 to 0.75 and the correlation of SNP effect values between meta-GWAS and mega-GWAS was 0.74, all showing good agreement. Collectively, even though there are differences in the integration of individual data or summary statistics, integrating data from multiple populations is an effective means of genetic argument for complex traits, especially mega-GWAS versus single-GWAS.

Integrating Multiple Database Resources to Elucidate the Gene Flow in Southeast Asian Pig Populations.

The domestic pig (Sus scrofa) and its subfamilies have experienced long-term and extensive gene flow, particularly in Southeast Asia. Here, we analyzed 236 pigs, focusing on Yunnan indigenous, European commercial, East Asian, and Southeast Asian breeds, using the Pig Genomics Reference Panel (PGRP v1) of Pig Genotype-Tissue Expression (PigGTEx) to investigate gene flow and associated complex traits by integrating multiple database resources. In this study, we discovered evidence of admixtures from European pigs into the genome of Yunnan indigenous pigs. Additionally, we hypothesized that a potential conceptual gene flow route that may have contributed to the genetic composition of the Diannan small-ear pig is a gene exchange from the Vietnamese pig. Based on the most stringent gene introgression scan using the fd statistic, we identified three specific loci on chromosome 8, ranging from 51.65 to 52.45 Mb, which exhibited strong signatures of selection and harbored the NAF1, NPY1R, and NPY5R genes. These genes are associated with complex traits, such as fat mass, immunity, and litter weight, in pigs, as supported by multiple bio-functionalization databases. We utilized multiple databases to explore the potential dynamics of genetic exchange in Southeast Asian pig populations and elucidated specific gene functionalities.

Exploring the mechanism of artificial selection signature in Chinese indigenous pigs by leveraging multiple bioinformatics database tools.

BACKGROUND: Chinese indigenous pigs in Yunnan exhibit considerable phenotypic diversity, but their population structure and the biological interpretation of signatures of artificial selection require further investigation. To uncover population genetic diversity, migration events, and artificial selection signatures in Chinese domestic pigs, we sampled 111 Yunnan pigs from four breeds in Yunnan which is considered to be one of the centres of livestock domestication in China, and genotyped them using Illumina Porcine SNP60K BeadChip. We then leveraged multiple bioinformatics database tools to further investigate the signatures and associated complex traits. RESULTS: Population structure and migration analyses showed that Diannanxiaoer pigs had different genetic backgrounds from other Yunnan pigs, and Gaoligongshan may undergone the migration events from Baoshan and Saba pigs. Intriguingly, we identified a possible common target of sharing artificial selection on a 265.09 kb region on chromosome 5 in Yunnan indigenous pigs, and the genes on this region were associated with cardiovascular and immune systems. We also detected several candidate genes correlated with dietary adaptation, body size (e.g., PASCIN1, GRM4, ITPR2), and reproductive performance. In addition, the breed-sharing gene MMP16 was identified to be a human-mediated gene. Multiple lines of evidence at the mammalian genome, transcriptome, and phenome levels further supported the evidence for the causality between MMP16 variants and the metabolic diseases, brain development, and cartilage tissues in Chinese pigs. Our results suggested that the suppression of MMP16 would directly lead to inactivity and insensitivity of neuronal activity and skeletal development in Chinese indigenous pigs. CONCLUSION: In this study, the population genetic analyses and identification of artificial selection signatures of Yunnan indigenous pigs help to build an understanding of the effect of human-mediated selection mechanisms on phenotypic traits in Chinese indigenous pigs. Further studies are needed to fully characterize the process of human-mediated genes and biological mechanisms.

BRF2 is mediated by microRNA-409-3p and promotes invasion and metastasis of HCC through the Wnt/ß-catenin pathway.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Its invasiveness and ability to metastasize contributes to an extremely high patient mortality. However, the molecular mechanisms that underlie the characteristics of HCC progression are not well understood. BRF2 has been shown to be an oncogene in a number of tumors; however, its role in HCC has not yet been thoroughly examined. In this study, we identified and validated BRF2 as an oncogene in HCC, providing a new insight into HCC pathogenesis and therapeutic possibilities. We showed that BRF2 expression was significantly upregulated in HCC cell lines and tissues, while BRF2 depletion suppressed HCC metastasis and invasion. We then examined the upstream regulation of BRF2 and identified miR-409-3p as being predicted to bind to the 3' UTR of BRF2. We used a luciferase activity assay and functional verification to show that BRF2 is downregulated by miR-409-3p. Finally, we used bioinformatic analysis to show that BRF2 may be related to early HCC development through the Wnt/ß-catenin signaling pathway.

MALAT1/ mir-1-3p mediated BRF2 expression promotes HCC progression via inhibiting the LKB1/AMPK signaling pathway.

BACKGROUND: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to play a vital role in the occurrence and development of various tumors. However, the underlying mechanism of MALAT1 in hepatocellular carcinoma (HCC) has not been thoroughly elucidated. METHODS: The expression levels of MALAT1 in HCC tissues and different cell lines were detected by qRT-PCR. Antisense oligonucleotides (ASO)-MALAT1 transfected cells were used to explore the biological effects of MALAT1 in HCC cells by cell counting kit 8 (CCK-8), colony formation, transwell, wound healing, and flow cytometry analysis. Western blotting was performed to measure AMPK and apoptosis-related protein levels. Dual-luciferase reporter assay was performed to verify the relationship between MALAT1 and its specific targets. RESULTS: We found that MALAT1 was upregulated in HCC, and MALAT1 knockdown in HCC cells inhibited cell proliferation, migration, and invasion and inhibited apoptosis in vitro. Further studies demonstrated that MALAT1 positively regulated the expression of transcription factor II B­related factor 2 (BRF2), which was associated with tumor recurrence, large tumor size, and poor prognosis in HCC. Mechanistically, MALAT1 was found to act as a competitive endogenous RNA to sponge has-miR-1-3p, which upregulated BRF2 expression. Knockdown of BRF2 inhibited the progression of HCC by activating the LKB1/AMPK signaling pathway. Overexpression of BRF2 reversed the inhibitory effect of MALAT1 knockdown on HCC cell viability. Moreover, ASO targeting MALAT1 inhibited the growth of xenograft tumors. CONCLUSIONS: Our results demonstrate a novel MALAT1/miR-1-3p/BRF2/LKB1/AMPK regulatory axis in HCC, which may provide new molecular therapeutic targets for HCC in the future.

Moiré Lattice in One-Dimensional Synthetic Frequency Dimension.

The moiré lattice has recently attracted broad interest in both solid-state physics and photonics where exotic phenomena in manipulating the quantum states are explored. In this work, we study the one-dimensional (1D) analogs of "moiré" lattices in a synthetic frequency dimension constructed by coupling two resonantly modulated ring resonators with different lengths. Unique features associated with the flatband manipulation as well as the flexible control of localization position inside each unit cell in the frequency dimension have been found, which can be controlled via the choice of flatband. Our work therefore provides insight into simulating moiré physics in 1D synthetic frequency space, which holds important promise for potential applications toward optical information processing.

Endovascular Stent Graft Repair for Mycotic Aorto-Iliac Aneurysm Due to Brucella.

PURPOSE: Brucella aneurysms are very rare but life-threatening, and a standard treatment approach has yet to be established. The current study aimed to assess the safety and efficacy of endovascular treatment for Brucella aneurysms. MATERIALS AND METHODS: The clinical data of 15 Brucella aortic-iliac aneurysm patients who underwent endovascular repair at 2 hospitals from January 2012 to December 2021 were retrospectively collected and analyzed. RESULTS: Fifteen patients (12 men and 3 women) with a mean age of 59.3 years were included. Fourteen patients (93.3%) had a history of exposure to animals (cattle and sheep). All patients had aortic or iliac pseudoaneurysms, 9 abdominal aortic aneurysms (AAAs), 4 iliac aneurysms, and 2 AAA combined with iliac aneurysms. Endovascular aneurysm repair (EVAR) was performed in all patients without conversion to open surgery. Six cases were treated for emergency surgery due to aneurysm rupture. The immediate technique success rate was 100%, with no postoperative death. Two cases had the iliac artery ruptured again after operation because of lack of antibiotic treatment and was given endovascular treatment again. Once brucellosis is diagnosed, antibiotic treatment with doxycycline and rifampicin was initiated for all the patients until 6 months after operation. All patients survived over a median follow-up period of 45 months. Follow-up computed tomography angiography showed that all stent grafts remained patent, with no endoleak. CONCLUSION: EVAR combined with antibiotics treatment is feasible, safe, and effective for Brucella aneurysms and represents a promising treatment option for these Brucella aneurysms. CLINICAL IMPACT: Brucella aneurysms are very rare but life-threatening, and a standard treatment approach has yet to be established. The traditional operation management strategy is surgical resection and debridement of the infected aneurysm and the surrounding tissues. However, open surgical management in these patients causes severe trauma with high surgical risks and mortality (13.3%-40%). We tried to treat Brucella aneurysms with endovascular therapy, and the technique success and survival rate of the operation reached 100%. EVAR combined with antibiotics treatment is feasible, safe, and effective for Brucella aneurysms and represents a promising treatment option for some mycotic aneurysms.

Maternal genetic diversity, differentiation and phylogeny of three white yak breeds/populations in China.

White yak is a unique economic livestock animal on the Qilian Mountains of Qinghai-Tibet Plateau (QTP). Here, 369 mitochondrial D-loop sequences from three Chinese white yak breeds/populations (Tianzhu, Menyuan and Huzhu) were comprehensively analyzed to indicate their maternal genetic diversity, differentiation and phylogenetic relationship. Our results showed that the haplotype diversity (Hd) was found to be highest in Tianzhu white yak (Hd ± SD = 0.9501 ± 0.0058), while the lowest was recorded in Huzhu white yak (Hd ± SD = 0.7178 ± 0.0474). Totally, the haplotype and nucleotide diversities of white yak were 0.9407 ± 0.0069 and 0.0187 ± 0.0094, respectively, indicating an abundant maternal genetic diversity in white yak. Estimates of FST (Fixation Index) values showed a high genetic differentiation between Tianzhu and Menyuan populations (FST = 0.2928, p < 0.05) as well as that between Tianzhu and Huzhu populations (FST = 0.2721, p < 0.05), but a moderate genetic differentiation between Menyuan and Huzhu populations (FST = 0.1352, p > 0.05) was observed. Cluster analysis based on FST values among populations indicated that the genetic relationship between Menyuan and Huzhu white yak was closer, but they had a far genetic relationship with Tianzhu white yak. Maternal phylogenetic analysis revealed that white yak represented two maternal lineages (I and II), suggesting two maternal origins. In addition, it is notable that taurine mtDNA haplotypes were detected in Tianzhu and Huzhu white yak populations, indicating taurine genetic introgression to some extent. Our study would provide useful information for the conservation and utilization of white yak.

Technologically feasible quasi-edge states and topological Bloch oscillation in the synthetic space.

The dimensionality of a physical system is one of the major parameters defining its physical properties. The recently introduced concept of synthetic dimension has made it possible to arbitrarily manipulate the system of interest and harness light propagation in different ways. It also facilitates the transformative architecture of system-on-a-chip devices enabling far reaching applications such as optical isolation. In this report, a novel architecture based on dynamically-modulated waveguide arrays with the Su-Schrieffer-Heeger configuration in the spatial dimension is proposed and investigated with an eye on a practical implementation. The propagation of light through the one-dimensional waveguide arrays mimics time evolution of the field in a synthetic two-dimensional lattice. The addition of the effective gauge potential leads to an exotic topologically protected one-way transmission along adjacent boundary. A cosine-shape isolated band, which supports the topological Bloch oscillation in the frequency dimension under the effective constant force, appears and is localized at the spatial boundary being robust against small perturbations. This work paves the way to improved light transmission capabilities under topological protections in both spatial and spectral regimes and provides a novel platform based on a technologically feasible lithium niobate platform for optical computing and communication.

Rich maternal and paternal genetic diversity and divergent lineage composition in wild yak (Bos mutus).

Wild yak (Bos mutus) is a vulnerable bovine species on the Qinghai-Tibetan Plateau (QTP). So far, most studies on molecular genetic diversity of wild yak have focused on autosomal and mtDNA variations based on small number of samples. In this study, we analyzed 84 D-loop and 24 whole mitogenome sequences of wild yak to further comprehensively explore its maternal genetic diversity and lineage composition. Meanwhile, using six yak Y-specific polymorphic markers (i.e., SRY4, USP9Y, UTY19, AMELY3, OFD1Y10 and INRA189), we assessed the paternal genetic diversity and lineage composition based on eight wild yak. Our results showed that wild yak exhibited abundant maternal genetic diversity with haplotype diversities of 0.9621 ± 0.0078 and 0.9928 ± 0.0144 in the D-loop and whole mitogenome sequences, respectively. Maternal phylogenetic analysis of wild yak uncovered three defined lineages (mt-I, mt-II and mt-III). Similarly, profuse paternal genetic diversity was observed in wild yak with Y-haplotype diversity (Hd) at 0.8214 ± 0.1007. Two Y-haplogroups (Y1 and Y2) with four Y-haplotypes (yH1-yH4) were identified in paternal phylogenetic analysis, indicating wild yak to be of two paternal lineages. This study of genetic diversity and lineage composition of wild yak would provide useful information for the genetic resource conservation and utilization of this vulnerable wild species.

Rich maternal and paternal genetic diversity and divergent lineage composition in wild yak (Bos mutus).

Wild yak (Bos mutus) is a vulnerable bovine species on the Qinghai-Tibetan Plateau. So far, most studies on the molecular genetic diversity of wild yak have focused on autosomal and mtDNA variations based on the small number of samples. In this study, we analyzed 84 D-loop and 24 whole mitogenome sequences of wild yak to further comprehensively explore its maternal genetic diversity and lineage composition. Meanwhile, using six yak Y-specific polymorphic markers (i.e., SRY4, USP9Y, UTY19, AMELY3, OFD1Y10 and INRA189), we assessed the paternal genetic diversity and lineage composition based on eight wild yak. Our results showed that wild yak exhibited abundant maternal genetic diversity with haplotype diversities of 0.9621 ± 0.0078 and 0.9928 ± 0.0144 in the D-loop and whole mitogenome sequences, respectively. Maternal phylogenetic analysis of wild yak uncovered three defined lineages (mt-I, mt-II and mt-III). Similarly, profuse paternal genetic diversity was observed in wild yak with Y-haplotype diversity at 0.8214 ± 0.1007. Two Y-haplogroups (Y1 and Y2) and four Y-haplotypes (yH1-yH4) were identified in paternal phylogenetic analysis, indicating wild yak to be of two paternal lineages. The present study of genetic diversity and lineage composition of wild yak would provide useful information for the genetic resource conservation and utilization of this vulnerable wild species.

Endovascular Stent Graft Repair for True and Post-Traumatic False Aneurysms of the Subclavian Artery.

OBJECTIVE: Subclavian artery aneurysms (SAAs) are uncommon but life-threatening, and a standard treatment approach has yet to be established. The current study aimed to assess the safety and efficacy of endovascular treatment for SAAs. METHODS: The clinical data of 18 SAA patients who underwent endovascular repair at 3 hospitals from January 2009 to December 2019 were retrospectively collected and analyzed. RESULTS: Eighteen patients (12 men and 6 women) with a mean age of 61 years were included. Six patients (33.3%) had a history of hypertension, and 5 (27.8%) had a history of chest trauma. Five patients (27.8%) were asymptomatic. Thirteen (72.2%) SAAs were true aneurysms, and the others (27.8%) were posttraumatic false aneurysms. Endovascular stent graft repair was performed in all patients without conversion to open surgery. The immediate technique success rate was 94.4%, with no postoperative death and only one case (5.6%) of endoleak that was observed on intraoperative angiography and later resolved spontaneously. All patients survived over a median follow-up time of 57 months. Follow-up imaging showed that all stent grafts remained patent, with no endoleak. CONCLUSIONS: Endovascular stent graft repair is feasible, safe, and effective for true and posttraumatic false SAAs and represents a promising treatment option for these SAAs.

Therapeutic management of isolated internal iliac artery aneurysms.

OBJECTIVE: Isolated internal iliac artery aneurysms (IIIAAs) are rare, life-threatening entities for which the optimal treatment strategy has not been established. This study aimed to evaluate the outcomes of open and endovascular treatment of IIIAAs. METHODS: IIIAA cases between January 2009 and March 2019 at two hospitals were retrospectively reviewed. Demographic, clinical, ancillary testing, treatment, and outcome data were collected and analyzed. RESULTS: Forty-two patients (37 men and 5 women) with a mean age of 71 years were included. Twenty-five patients (60%) had a history of hypertension. Twenty-two patients (52%) were asymptomatic, and 16 (38%) presented with abdominal pain (12 with ruptured aneurysms). The 42 included patients had 43 treated IIIAAs. The following surgical techniques were used: surgical resection (n = 6), endovascular coil embolization (n = 12), endovascular stent graft placement across the internal iliac artery origin (n = 8 with 9 aneurysms), and combined coil embolization and stent graft placement (n = 16). The immediate technical success rate was 67%, 67%, and 88% for embolization, stent graft placement, and combined method, respectively. Open surgery was associated with the longest operative time and hospital stay. Overall 30-day mortality was 5% for all patients and 17% for patients with ruptured IIIAAs. Buttock claudication occurred in 7 of 40 patients who survived (18%). The median follow-up time was 56 months. The combined approach was associated with the lowest rates of endoleak (6% vs 25% and 29%) and reintervention (6% vs 17% and 29%) of the three endovascular methods. CONCLUSIONS: Endovascular coil embolization with stent graft placement is a feasible, safe, and effective treatment approach for large IIIAAs without adequate aneurysm necks.

A Modified Loop Snare Technique for Difficult Retrievals of Inferior Vena Cava Filter and Migrated Coil.

The aim of this study was to evaluate the safety and efficacy of a modified loop snare technique for retrieval of difficult inferior vena cava (IVC) filters and migrated coils.A retrospective review of Günther Tulip filter retrievals between January 2014 and February 2017 was performed. A total of 316 IVC filter retrievals were attempted. In 25 cases, the standard technique had failed and our modified loop snare technique was subsequently attempted in 21 of these patients.The retrievals were successful in 20 cases (mean dwell time, 42.6 days, range, 14-102 days). The dwell time of the one failure was 46 days. The retrieval rate increased from 92.1% with the standard technique to 98.4% with the combination of the standard and modified loop snare technique. Unsuccessful retrieval was due to migration and endothelialization of the filter. This technique can also be used to remove migrated coils which cannot be captured by standard techniques. There were no complications from the retrievals.Tilt and endothelialization of filters are the main factors resulting in unsuccessful retrievals with the standard technique. In the present study, we describe an alternative technique for difficult IVC filter retrievals, which can also be used to capture migrated coils and occluders in the aorta and heart.

Broadband sum-frequency generation using d33 in periodically poled LiNbO3 thin film in the telecommunications band.

We demonstrate the first, to the best of our knowledge, type-0 broadband sum-frequency generation (SFG) based on single-crystal periodically poled LiNbO3 (PPLN) thin film. The broad bandwidth property was largely tuned from mid-infrared region to the telecommunications band by engineering the thickness of PPLN from bulk crystal to nanoscale. It provides SFG a solution with both broadband and high efficiency by using the highest nonlinear coefficient d33 instead of d31 in type-I broadband SFG or second-harmonic generation. The measured 3 dB upconversion bandwidth is about 15.5 nm for a 4 cm long single crystal at 1530 nm wavelength. It can find applications in chip-scale spectroscopy, quantum information processing, LiNbO3-thin-film-based microresonator and optical nonreciprocity devices, etc.

Smad3 Sensitizes Hepatocelluar Carcinoma Cells to Cisplatin by Repressing Phosphorylation of AKT.

BACKGROUND: Heptocelluar carcinoma (HCC) is insensitive to chemotherapy due to limited bioavailability and acquired drug resistance. Smad3 plays dual roles by inhibiting cell growth initially and promoting the progression of advanced tumors in HCC. However, the role of smad3 in chemosensitivity of HCC remains elusive. METHODS: The role of smad3 in chemosensitivity of HCC was measured by cell viability, apoptosis, plate colony formation assays and xenograft tumor models. Non-smad signaling was detected by Western blotting to search for the underlying mechanisms. RESULTS: Smad3 enhanced the chemosensitivity of HCC cells to cisplatin. Smad3 upregulated p21(Waf1/Cip1) and downregulated c-myc and bcl2 with the treatment of cisplatin. Moreover, overexpression of smad3 repressed the phosphorylation of AKT, and vice versa. Inhibition of PI3K/AKT pathway by LY294002 restored chemosensitivity of smad3-deficiency cells to cisplatin in HCC. CONCLUSION: Smad3 sensitizes HCC cells to the effects of cisplatin by repressing phosphorylation of AKT and combination of inhibitor of AKT pathway and conventional chemotherapy may be a potential way to solve drug resistance in HCC.

Optical half-adder and half-subtracter employing the Pockels effect.

The Pockels effect in periodically poled lithium niobate made it possible to switch optical signals between two orthogonal optical linear polarizations of the vertical and horizontal polarization states. Based on this effect, we demonstrated polarization-based binary optical logic gates: AND, and OR gates. By combining these basic gates with other polarization-based optical logic gates such as XOR gate accomplished in our previous researches, half-adder and half-subtracter of digital signals with a high extinction ratio of about 10dB have been demonstrated in our experiment, which made it possible to run more complex logical calculus.

Tunable temporal gap based on simultaneous fast and slow light in electro-optic photonic crystals.

We demonstrated a tunable temporal gap based on simultaneous fast and slow light in electro-optic photonic crystals. The light experiences an anomalous dispersion near the transmission center and a normal dispersion away from the center, where it can be accelerated and slowed down, respectively. We also obtained the switch between fast and slow light by adjusting the external electric filed. The observed largest temporal gap is 541 ps, which is crucial in practical event operation inside the gap. The results offer a new solution for temporal cloak.

[Scrotal calculi: advances in clinical research].

Scrotal calculi are freely mobile calcified bodies or stones located between the layers of the tunica vaginalis of the testis. The literature on this relatively rare benign lesion consists mostly of case reports. In most cases, scrotal calculi are found incidentally during ultrasound examination. Now with the application of high-frequency ultrasonography, the detection rate of scrotal calculi is gradually increasing. This article summarizes the etiology, pathogenesis, clinical manifestations, diagnosis, and treatment of scrotal calculi.