Sildenafil increases AAV9 transduction after a systemic administration and enhances AAV9-dystrophin therapeutic effect in mdx mice.

Adeno-associated virus (AAV) vectors have been successfully used to deliver genes for treating rare diseases. However, the systemic administration of high AAV vector doses triggers several adverse effects, including immune response, the asymptomatic elevation of liver transaminase levels, and complement activation. Thus, improving AAV transduction and reducing AAV dosage for treatment is necessary. Recently, we found that a phosphodiesterase-5 inhibitor significantly promoted AAV9 transduction in vitro by regulating the caveolae and macropinocytosis pathways. When AAV9-Gaussian luciferase (AAV9-Gluc) and AAV9-green fluorescent protein (AAV9-GFP) were injected intravenously into mice pre-treated with sildenafil, the expressions of Gluc in the plasma and GFP in muscle tissues significantly increased (P < 0.05). Sildenafil also improved Evans blue permeation in tissues. Additionally, we found that sildenafil promoted Treg proliferation, inhibited B-cell activation, and decreased anti-AAV9 IgG levels (P < 0.05). Furthermore, sildenafil significantly promoted Duchenne muscular dystrophy gene therapy efficacy using AAV9 in mdx mice; it increased micro-dystrophin gene expression, forelimb grip strength, and time spent on the rotarod test, decreased serum creatine kinase levels, and ameliorated histopathology by improving muscle cell morphology and reducing fibrosis (P < 0.05). These results show that sildenafil significantly improved AAV transduction, suppressed the levels of anti-AAV9 IgG, and enhanced the efficacy of gene therapy.

Bacillus subtilis and Enterococcus faecium co-fermented feed alters antioxidant capacity, muscle fibre characteristics and lipid profiles of finishing pigs.

This study aimed to assess how Bacillus subtilis and Enterococcus faecium co-fermented feed (FF) affects the antioxidant capacity, muscle fibre types and muscle lipid profiles of finishing pigs. In this study, a total of 144 Duroc × Berkshire × Jiaxing Black finishing pigs were randomly assigned into three groups with four replicates (twelve pigs per replication). The three treatments were a basal diet (0 % FF), basal diet + 5 % FF and basal diet + 10 % FF, respectively. The experiment lasted 38 d after 4 d of acclimation. The study revealed that 10 % FF significantly increased the activity of superoxide dismutase (SOD) and catalase (CAT) compared with 0 % FF group, with mRNA levels of up-regulated antioxidant-related genes (GPX1, SOD1, SOD2 and CAT) in 10 % FF group. 10 % FF also significantly up-regulated the percentage of slow-twitch fibre and the mRNA expression of MyHC I, MyHC IIa and MyHC IIx, and slow MyHC protein expression while reducing MyHC IIb mRNA expression. Lipidomics analysis showed that 5 % FF and 10 % FF altered lipid profiles in longissimus thoracis. 10 % FF particularly led to an increase in the percentage of TAG. The Pearson correlation analysis indicated that certain molecular markers such as phosphatidic acid (PA) (49:4), Hex2Cer (d50:6), cardiolipin (CL) (72:8) and phosphatidylcholine (PC) (33:0e) could be used to indicate the characteristics of muscle fibres and were closely related to meat quality. Together, our findings suggest that 10 % FF improved antioxidant capacity, enhanced slow-twitch fibre percentage and altered muscle lipid profiles in finishing pigs.

Surface Acoustic Wave Sensors for Wireless Temperature Measurements above 1200 Degree Celsius.

High-temperature wireless sensing is crucial for monitoring combustion chambers and turbine stators in aeroengines, where surface temperatures can reach up to 1200 °C. Surface Acoustic Wave (SAW) temperature sensors are an excellent choice for these measurements. However, at extreme temperatures, they face issues such as agglomeration and recrystallization of electrodes, leading to loss of conductivity and reduced quality factor, hindering effective wireless signal transmission. This study develops an LGS SAW sensor with a Pt-10%Rh/Zr/Pt-10%Rh/Zr/Pt-10%Rh/Zr multilayer composite electrode structure to address these challenges. We demonstrate that the sensor can achieve wireless temperature measurements from room temperature to 1200 °C with an accuracy of 1.59%. The composite electrodes excite a quasi-shear wave on the LGS substrate, maintaining a Q-factor of 3526 at room temperature, providing an initial assurance for the strength of the wireless interrogation echo signal. The sensor operates stably for 2.18 h at 1200 °C before adhesion loss between the composite electrode and the substrate causes a sudden increase in resonant frequency. This study highlights the durability of the proposed electrode materials and structure at extreme temperatures and suggests future research to improve adhesion and extend the sensor's lifespan, thereby enhancing the reliability and effectiveness of high-temperature wireless sensing in aerospace applications.

Thickness effect of 2D PdSe2film on performance of PdSe2/Si heterostructure photodetectors.

Two-dimensional (2D) PdSe2film has the characteristics of adjustable bandgap, high carrier mobility, and high stability. Photodetector (PD) based on 2D PdSe2exhibits wide spectral self-driving features, demonstrating enormous potential in the field of optical detection. Here, we design and fabricate PdSe2/Si heterojunction PDs with various thicknesses of the PdSe2films from 10 to 35 nm. Due to the enhancement of light absorption capacity and built-in electric field of heterojunction, the photodetector with thicker PdSe2film can generate more photo-generated carriers and effectively separate them to form a large photocurrent, thus showing more excellent photodetection performance. The responsivity and specific detectivity of the PdSe2/Si PDs with 10 nm, 20 nm, and 35 nm PdSe2films are 2.12 A W-1and 6.72 × 109Jones, 6.17 A W-1and 1.95 × 1010Jones, and 8.02 A W-1and 2.54 × 1010Jones, respectively (808 nm illumination). The PD with 35 nm PdSe2film exhibits better performance than the other two PDs, with the rise/fall times of 15.8µs/138.9µs atf= 1 kHz and the cut-off frequency of 8.6 kHz. Furthermore, we demonstrate that the properties of PdSe2/Si PD array have excellent uniformity and stability at room temperature and shows potential for image sensing in the UV-vis-NIR wavelength range.

Dysiscalarones A-E, scalarane sesterterpenoids with nitric oxide production inhibitory activity from marine sponge Dysidea granulosa.

Dysiscalarones A-E (1-5), five new scalarane-type bishomoscalarane sesterterpenoids, were isolated from marine sponge Dysidea granulosa collected from the South China Sea, together with two known ones, honulactone A (6) and phyllofolactone I (7). The new structures were determined by extensive spectroscopic analysis including HR-ESI-MS and 1D and 2D NMR data, and their absolute configurations were assigned by single crystal X-ray diffraction analyses. The inhibitory activity of all the seven isolates on the production of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in mouse RAW 264.7 macrophages was evaluated. Of these metabolites, dysiscalarones A-B (1-2), honulactone A (6), and phyllofolactone I (7) showed inhibitory activities with respective IC50 values of 16.4, 18.5, 2.6, and 3.7 µM, which suggested that the γ-methylated α,ß-unsaturated γ-lactone might be the functional group. In addition, all the seven metabolites showed no significant cytotoxicity against lung cancer PC9 cell line at the concentration of 20 µM.

Strong emissive nanofibers of organogels for the detection of volatile acid vapors.

Two L-phenylalanine derivatives with 5,8-bis(2-(carbazol-3-yl)vinyl)quinoxaline (PCQ) and 5,8-bis[2-(carbazol-3-yl)]-2,3-dimethylquinoxaline (DCQ) as fluorophores were synthesized, and their photophysical properties were measured and compared. The two compounds were found to gelate some organic solvents and self-assemble into 1D nanofibers in gels. The wet gel of PCQ emitted a weak orange fluorescence, but the DCQ gel had a strong green one. This result can be due to the presence of two methyl groups and the nonplanar conformation of fluorophore in DCQ. The gel film of DCQ also showed significantly stronger fluorescence than that of PCQ. Thus, the wet gel and xerogel film of DCQ were selected to study their sensing properties to acids. The yellow wet gel of DCQ transformed into a brown sol upon the addition of 0.2 equiv trifluoroacetic acid (TFA), accompanied by emission quenching. The xerogel film of DCQ rapidly responded to volatile acids, such as TFA, HCl, and HOAc. The fluorescence of the xerogel film was gradually quenched with increased concentration of volatile acid vapors. The fibrous film exhibited low detection limits for volatile acid. The detection limits of the thin films for TFA, HCl, and HOAc reached 43, 122, and 950 ppb, respectively.

A high-performance broadband phototransistor array of a PdSe2/SOI Schottky junction.

There is great interest in the incorporation of novel two-dimensional materials into Si-based technologies to realize multifunctional optoelectronic devices via heterogeneous integration. Here, we demonstrate a gate-tunable, self-driven, high-performance broadband phototransistor array based on a PdSe2/Si Schottky junction, which is fabricated by pre-depositing a semi-metallic PdSe2 film on a SOI substrate. In addition, thanks to the zero bandgap of the PdSe2 material and the PdSe2/Si vertical heterostructure, the prepared phototransistor exhibits pronounced photovoltaic properties in a wide spectral range from ultraviolet to near-infrared. The responsivity, specific detectivity and response time of the device at the incident light wavelength of 808 nm are 1.15 A W-1, 9.39 × 1010 Jones, and 27.1/40.3 µs, respectively, which are better than those of previously reported PdSe2-based photodetectors. The photoelectric performance can be further improved by applying an appropriate gate voltage to the phototransistor and the responsivity of the device increases to 1.61 A W-1 at VG = 5 V. We demonstrate the excellent imaging capabilities of a 4 × 4 array image sensor using PdSe2/SOI phototransistors under 375 nm, 532 nm, and 808 nm laser sources.

Pig pangenome graph reveals functional features of non-reference sequences.

BACKGROUND: The reliance on a solitary linear reference genome has imposed a significant constraint on our comprehensive understanding of genetic variation in animals. This constraint is particularly pronounced for non-reference sequences (NRSs), which have not been extensively studied. RESULTS: In this study, we constructed a pig pangenome graph using 21 pig assemblies and identified 23,831 NRSs with a total length of 105 Mb. Our findings revealed that NRSs were more prevalent in breeds exhibiting greater genetic divergence from the reference genome. Furthermore, we observed that NRSs were rarely found within coding sequences, while NRS insertions were enriched in immune-related Gene Ontology terms. Notably, our investigation also unveiled a close association between novel genes and the immune capacity of pigs. We observed substantial differences in terms of frequencies of NRSs between Eastern and Western pigs, and the heat-resistant pigs exhibited a substantial number of NRS insertions in an 11.6 Mb interval on chromosome X. Additionally, we discovered a 665 bp insertion in the fourth intron of the TNFRSF19 gene that may be associated with the ability of heat tolerance in Southern Chinese pigs. CONCLUSIONS: Our findings demonstrate the potential of a graph genome approach to reveal important functional features of NRSs in pig populations.

A Plasmonic Optoelectronic Resistive Random-Access Memory for In-Sensor Color Image Cryptography.

The optoelectronic resistive random-access memory (RRAM) with the integrated function of perception, storage and intrinsic randomness displays promising applications in the hardware level in-sensor image cryptography. In this work, 2D hexagonal boron nitride based optoelectronic RRAM is fabricated with semitransparent noble metal (Ag or Au) as top electrodes, which can simultaneous capture color image and generate physically unclonable function (PUF) key for in-sensor color image cryptography. Surface plasmons of noble metals enable the strong light absorption to realize an efficient modulation of filament growth at nanoscale. Resistive switching curves show that the optical stimuli can impede the filament aggregation and promote the filament annihilation, which originates from photothermal effects and photogenerated hot electrons in localized surface plasmon resonance of noble metals. By selecting noble metals, the optoelectronic RRAM array can respond to distinct wavelengths and mimic the biological dichromatic cone cells to perform the color perception. Due to the intrinsic and high-quality randomness, the optoelectronic RRAM can produce a PUF key in every exposure cycle, which can be applied in the reconfigurable cryptography. The findings demonstrate an effective strategy to build optoelectronic RRAM for in-sensor color image cryptography applications.

Anion response of organogels: dependence on intermolecular interactions between gelators.

Being different from common sensing molecules existing as monomer in solution, the gelators as sensing molecules self-assembled together in gels. Therefore, the interaction strength between gelators is believed as an important factor for gels to recognize selectively anions. In this paper, we choose two gelators, presenting similar binding sites for anions, but different strengths in intermolecular interaction. Moreover, their anion responsive behaviors in organogels were examined by observing phase state and measuring UV-vis and fluorescence spectra. We found that the organogel formed by 2 with strong intermolecular interaction could selectively recognize fluoride anion. However, the gels of 1 could be transformed into sol phases by addition of F(-), Cl(-), Br(-), AcO(-) and H(2)PO(4)(-) because of the small aggregate constant of 1 in o-dichlorobenzene, presenting poor selectivity. Moreover, their UV-vis and emission spectra acting as testing methods also suggested the same conclusion.

Modal-Transition-Induced Valleys of K2 in Piezoelectric Bilayer Laterally Vibrating Resonators.

Piezoelectric Laterally Vibrating Resonators (LVRs) have attracted significant attention as a potential technology for next-generation wafer-level multi-band filters. Piezoelectric bilayer structures such as Thin-film Piezoelectric-on-Silicon (TPoS) LVRs which aim to increase the quality factor (Q) or aluminum nitride and silicon dioxide (AlN/SiO2) composite membrane for thermal compensation have been proposed. However, limited studies have investigated the detailed behaviors of the electromechanical coupling factor (K2) of these piezoelectric bilayer LVRs. Herein, AlN/Si bilayer LVRs are selected as an example, we observed notable degenerative valleys in K2 at specific normalized thicknesses using two-dimensional finite element analysis (FEA), which has not been reported in the previous studies of bilayer LVRs. Moreover, the bilayer LVRs should be designed away from the valleys to minimize the reduction in K2. Modal-transition-induced mismatch between electric and strain fields of AlN/Si bilayer LVRs are investigated to interpret the valleys from energy considerations. Furthermore, the impact of various factors, including electrode configurations, AlN/Si thickness ratios, the Number of Interdigitated Electrode (IDT) Fingers (NFs), and IDT Duty Factors (DFs), on the observed valleys and K2 are analyzed. These results can provide guidance for the designs of piezoelectric LVRs with bilayer structure, especially for LVRs with a moderate K2 and low thickness ratio.

Integration of Selection Signatures and Protein Interactions Reveals NR6A1, PAPPA2, and PIK3C2B as the Promising Candidate Genes Underlying the Characteristics of Licha Black Pig.

Licha black (LI) pig has the specific characteristics of larger body length and appropriate fat deposition among Chinese indigenous pigs. Body length is one of the external traits that affect production performance, and fat deposition influences meat quality. However, the genetic characteristics of LI pigs have not yet been systematically uncovered. Here, the genomic information from 891 individuals of LI pigs, commercial pigs, and other Chinese indigenous pigs was used to analyze the breed characteristics of the LI pig with runs of homozygosity, haplotype, and FST selection signatures. The results showed the growth traits-related genes (i.e., NR6A1 and PAPPA2) and the fatness traits-related gene (i.e., PIK3C2B) were the promising candidate genes that closely related to the characteristics of LI pigs. In addition, the protein-protein interaction network revealed the potential interactions between the promising candidate genes and the FASN gene. The RNA expression data from FarmGTEx indicated that the RNA expression levels of NR6A1, PAPPA2, PIK3C2B, and FASN were highly correlated in the ileum. This study provides valuable molecular insights into the mechanisms that affect pig body length and fat deposition, which can be used in the further breeding process to improve meat quality and commercial profitability.

Fermented mixed feed regulates intestinal microbial community and metabolism and alters pork flavor and umami.

This study aimed to determine the effects of fermented mixed feed (FMF) supplementation (0%, 5% and 10%) on the intestinal microbial community and metabolism, and the compositions of volatile flavor compounds and inosine monophosphate (IMP) contents in the longissimus thoracis. In this study, 144 finishing pigs (Duroc × Berkshire × Jiaxing Black) were randomly allocated to 3 groups with 4 replicate pens per group and 12 pigs per pen. The experiment lasted 38 days after 4 days of acclimation. The 16S rRNA gene sequences and an untargeted metabolomics analysis showed FMF altered the profiles of microbes and metabolites in the colon. Heracles flash GC e-nose analysis showed that 10% FMF (treatment 3) had a greater influence on the compositions of volatile flavor compounds than 5% FMF (treatment 2). Compared to 0% FMF (treatment 1), the contents of total aldehydes, (E,E)-2,4-nonadienal, dodecanal, nonanal and 2-decenal were significantly increased by treatment 3, and treatment 3 increased IMP concentrations and gene expressions related to its synthesis. Correlations analysis showed significantly different microbes and metabolites had strong correlations with the contents of IMP and volatile flavor compounds. In conclusion, treatment 3 regulated intestinal microbial community and metabolism, that in turn altered the compositions of volatile compounds, which contributed to improving pork flavor and umami.

Tuina for perimenopausal insomnia: A protocol for systematic review and meta-analysis.

BACKGROUND: Insomnia in perimenopausal women has a negative impact on quality of life and increases health care costs. With the increasing incidence of the disease, Tuina has been accepted by perimenopausal women. The purpose of this study is to explore the effectiveness and safety of Tuina for perimenopausal insomnia. METHODS: We will search 9 electronic databases: Chinese Biomedical Literature Database, Cochrane Library, China National Knowledge Infrastructure, EMBASE, MEDLINE, Web of Science, PubMed, Wan fang, Chinese Scientific Journal Database, and 1 clinical trials register platform: WHO International Clinical Trials Registry Platform. All relevant randomized controlled trial using Tuina for perimenopausal insomnia will be included. Two reviewers will independently screen date, and meta-analysis will be performed with RevMan (V5.3.5) software. RESULTS: This study will provide an evidence of Tuina for perimenopausal insomnia. CONCLUSION: This study will provide a reliable evidence for the evaluation of the efficacy and side effects of Tuina in the treatment of perimenopausal insomnia. PROSPERO REGISTRATION NUMBER: CRD42021259017. ETHICS AND DISSEMINATION: This systematics review will evaluate the efficacy and safety of tuina in the treatment of perimenopausal insomnia. Since all the data included were published, the systematic review did not require ethical approval.

Acupuncture combined with traditional Chinese medicine for knee osteoarthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: With the aging of society, the incidence of knee osteoarthritis (KOA) is increasing year by year, which seriously affects the quality of life. Acupuncture therapy has been widely used in the treatment of osteoarthritis, but there is no complete systematic review on acupuncture combined with traditional Chinese medicine. Therefore, this study aims to clarify the efficacy and safety of acupuncture combined with traditional Chinese medicine in the treatment of KOA through systematic review and meta-analysis. METHODS: A structured and systematic literature search will be conducted in the following databases up to March, 20, 2022: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific and Journal Database, Wan Fang database and 2 clinical trials register platforms: Chinese Clinical Trial Registry, ClinicalTrials.gov (www.ClinicalTrials.gov/). We will use the Review Manager 5.4 software provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed the outcome measures. RESULTS: This meta-analysis further established the efficacy of acupuncture combined with traditional Chinese medicine in the treatment of KOA. CONCLUSION: This meta-analysis aims to investigate the efficacy of acupuncture combined with traditional Chinese medicine on patients with KOA and provide reliable evidence. To provide more options for clinicians and patients in the treatment of KOA.

Tuina for shoulder pain after stroke: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-stroke shoulder pain is a relatively common complication in stroke patients, with an incidence of 16% to 84% and poor outcomes with anti-inflammatory or sedative medications. This study will evaluate the results of a randomized controlled trial to determine the effectiveness and safety of Tuina in the treatment of post-stroke shoulder pain. METHODS: The Chinese and English search strategies were used to search China National Knowledge Infrastructure, Chinese Scientific Journal Database, Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, PubMed, Wanfang Database, and Web of Science were used to search seven databases. All eligible studies published on or before September 15, 2022, will be selected. To improve the validity of this study, only clinical randomized controlled trials related to the use of Tuina for post-stroke shoulder pain will be included. The screening will be performed by 2 independent reviewers and data synthesis, bias analysis, subgroup analysis, and meta-analysis will be performed using RevMan (V.5.4) software. RESULTS: The study will provide a high-quality evaluation of the effectiveness and safety of Tuina in the treatment of post-stroke shoulder pain. CONCLUSION: This systematic review will provide evidence to determine whether Tuina is an effective and safe intervention for treating patients with post-stroke shoulder pain.PROSPERO registration number: CRD42022360401.

A Power-Harvesting CGM Chiplet Featuring Silicon-Based Enzymatic Glucose Sensor.

Diabetes has become a leading cause of death and disability in the past decades. Continuous glucose monitoring (CGM) is a prevailing technique to determine the glucose level and provide in-time treatment. However, conventional CGM systems combine an electrochemical sensor with a CMOS chip, suffering from bulky size and interface issues. Integrating the CGM sensor on silicon is potential to miniaturize the CGM system and reduce the cost, while the recent silicon-based sensors show limited detection range and sensitivity. In this work, we present a silicon-based CGM chip let with wireless power transfer (WPT) and real-time wireless telemetry. Fabricated on a single silicon substrate, the chiplet consists of a silicon-based CGM sensor, a power-harvesting wireless-telemetry chip, and a silicon-based antenna. Measured results show that the chip let achieves a sensitivity of 4 µA.mM.cm-2 and a linear detection range of 0-10 mM. Based on WPT and backscattering communication, the chip let consumes 18.8 µ W power in glucose telemetry.

Abdominal massage: A review of clinical and experimental studies from 1990 to 2021.

OBJECTIVE: To systematically review the current state and holistic application of abdominal massage (AM). DESIGN: A systematic review of qualitative evidence was conducted. All English articles exploring the topic of AM that had been published until the end of June 2021 were retrieved. DATA SOURCES: The PubMed, Cochrane library, and Embase databases were accessed. Some original texts were obtained from Google Scholar. DATA EXTRACTION AND SYNTHESIS: Two authors independently evaluated all search data to identify relevant studies. Disagreements were settled by discussion with a third author. Results were independently extracted into standardized sheets and checked for accuracy. MAIN RESULTS: A total of 107 full-text reports were eligible for inclusion. Adult digestive disorders, pediatric disorders, gynecological disorders, obstetric disorders, metabolic disorders, psychological disorders, the side effects of AM, and animal experiments accounted for 49.53%, 14.02%, 7.48%, 7.48%, 4.67%, 4.67%, 5.61%, and 6.54% of all these papers, respectively, with most reports focusing on clinical studies. CONCLUSION: The variety of diseases treated with AM is gradually increasing, and the treatment programs of AM for many diseases are being gradually optimized. Different forms of AM, especially mechanical AM, have been widely studied; the side effects of AM have also been considered; and the possible mechanisms of AM therapy continue to be discovered. In general, AM is an effective and safe therapy and can be widely used in various diseases, but further studies are necessary to clarify the mechanism of AM for different diseases. In the future, AM could become an even safer, more popular, and more modern therapy.

Tuina combined with diet and exercise for simple obesity: A protocol for systematic review.

BACKGROUND: The incidence of simple obesity is increasing annually, with the number of obese people in all age groups increasing significantly. Obesity has become an important public health concern. Simple obesity affects not only appearance but also health. Obesity has an increasing impact on individuals, families, and society. Therefore, the treatment of obesity is becoming increasingly important. Prior studies have shown that Tuina combined with diet and exercise is capable of producing improvements in body weight and fasted health markers. In recent years, there are many clinical studies on the intervention of simple obesity by Tuina combined with diet and exercise, however, no study systematically evaluated the clinical efficacy. The purpose of this study is to evaluate its effects of Tuina combined with diet and exercise on people with simple obesity. METHODS: We will search the following electronic databases: PubMed, EMBASE, MEDLINE, Web of science, Cochrane Library, WanFang Data, CBM, CNKI, and VIP from the inception of the coverage of these databases to December 2021. Randomized controlled clinical trials related to Tuina combined with diet and exercise intervention on simple obesity will be included. Cochrane's collaboration tool will be used to assess the quality of the studies. RevMan 5.3 software will be used for the data analysis. RESULTS: This study will provide a standardized evaluation for the efficacy of Tuina combined with diet and exercise for simple obesity. CONCLUSION: The conclusion of this study will provide evidence for the safety and effectiveness of Tuina combined with diet and exercise on weight loss. ETHICS AND DISSEMINATION: Ethical approval is not required for systematic review and meta- analysis. The results of this review will be disseminated in a peer-review journal. PROSPERO REGISTRATION NUMBER: INPLASY202210079.

PHARP: a pig haplotype reference panel for genotype imputation.

Pigs not only function as a major meat source worldwide but also are commonly used as an animal model for studying human complex traits. A large haplotype reference panel has been used to facilitate efficient phasing and imputation of relatively sparse genome-wide microarray chips and low-coverage sequencing data. Using the imputed genotypes in the downstream analysis, such as GWASs, TWASs, eQTL mapping and genomic prediction (GS), is beneficial for obtaining novel findings. However, currently, there is still a lack of publicly available and high-quality pig reference panels with large sample sizes and high diversity, which greatly limits the application of genotype imputation in pigs. In response, we built the pig Haplotype Reference Panel (PHARP) database. PHARP provides a reference panel of 2012 pig haplotypes at 34 million SNPs constructed using whole-genome sequence data from more than 49 studies of 71 pig breeds. It also provides Web-based analytical tools that allow researchers to carry out phasing and imputation consistently and efficiently. PHARP is freely accessible at http://alphaindex.zju.edu.cn/PHARP/index.php . We demonstrate its applicability for pig commercial 50 K SNP arrays, by accurately imputing 2.6 billion genotypes at a concordance rate value of 0.971 in 81 Large White pigs (~ 17 × sequencing coverage). We also applied our reference panel to impute the low-density SNP chip into the high-density data for three GWASs and found novel significantly associated SNPs that might be casual variants.