Ethyl caffeate attefnuates Aß-induced toxicity in Caenorhabditis elegans AD models via the insulin/insulin-like growth factor-1 signaling pathway.

The pathogenesis of Alzheimer's disease (AD), a multifactorial progressive neurodegenerative disease associated with aging, is unclear. Ethyl caffeate is a plant polyphenol that has been reported to have neuroprotective effects, but the mechanisms by which it acts are unclear. In this study, for the first time, we investigated the molecular mechanism of its anti-AD properties using the Caernorhabditis elegans model. The results of our experiments showed that ethyl caffeate delayed the paralysis symptoms of CL4176 to a different extent and reduced the exogenous 5-hydroxytryptophan-induced paralysis phenotype. Further studies revealed that ethyl caffeate lowered Aß plaques and depressed the expression of Aß monomers and oligomers, but did not influence the mRNA levels of Aß. Moreover, it was able to bring paraquat-induced ROS levels down to near-standard conditions. Real-time quantitative PCR experiment showed a significant upregulation of the transcript abundance of daf-16, skn-1 and hsf-1, key factors associated with the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway (IIS), and their downstream genes sod-3, gst-4 and hsp-16.2. It was further shown that ethyl caffeate activated the translocation of DAF-16 and SKN-1 from the cytoplasm to the nucleus and enhanced the expression of sod-3::GFP, gst-4::GFP and hsp-16.2::GFP in transgenic nematodes. This meant that the protection against Aß toxicity by ethyl caffeate may be partly through the IIS signaling pathway. In addition, ethyl caffeate suppressed the aggregation of polyglutamine proteins in AM141, which indicated a potential protective effect against neurodegenerative diseases based on abnormal folding and aggregation of amyloid proteins. Taken together, ethyl caffeate is expected to develop as a potential drug for the management of AD.

Identification of Gut Microbiota Affecting Fiber Digestibility in Pigs.

Dietary fiber plays an important role in porcine gut health and welfare. Fiber is degraded by microbial fermentation in the intestine, and most gut microbiota related to fiber digestibility in pigs are worth pursuing. The aim of this study was to identify gut microbiota associated with the apparent total tract digestibility (ATTD) of neutral detergent fiber (NDF) and of acid detergent fiber (ADF) in pigs. Large phenotypic variations in the ATTD of NDF and of ADF were separately found among 274 Suhuai pigs. Microbial community structures were significantly different between high and low fiber digestibility groups. Fourteen genera separately dominated the communities found in the high ATTD (H-AD) of NDF and ADF samples and were in very low abundance in the low ATTD (L-AD) of NDF and ADF samples. In conclusion, norank_f__Bacteroidales_S24-7_group (p < 0.05), Ruminococcaceae_UCG-005 (p < 0.05), unclassified_f__Lachnospiraceae (p < 0.05), Treponema_2 (p < 0.01), and Ruminococcaceae_NK4A214_group (p < 0.01) were the main genera of gut microbiota affecting the ATTD of NDF in pigs. Christensenellaceae_R-7_group (p < 0.01), Treponema_2 (p < 0.05), Ruminococcaceae_NK4A214_group (p < 0.05), Ruminococcaceae_UCG-002 (p < 0.05), and [Eubacterium]_coprostanoligenes_group (p < 0.05) were the main genera of gut microbiota affecting the ATTD of ADF in pigs. The most important functions of the above different potential biomarkers were: carbohydrate transport and metabolism, general function prediction only, amino acid transport and metabolism, cell wall/membrane/envelope biogenesis, translation, transcription, replication, energy production and conversion, signal transduction mechanisms, and inorganic ion transport and metabolism. The most important metabolic pathways of the above different potential biomarkers were: membrane transport, carbohydrate metabolism, amino acid metabolism, replication and repair, translation, cell motility, energy metabolism, poorly characterized, nucleotide metabolism, metabolism of cofactors and vitamins, and cellular processes and signaling.

Diterpenoid Caesalmin C Delays Aß-Induced Paralysis Symptoms via the DAF-16 Pathway in Caenorhabditis elegans.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world. However, there is no effective drug to cure it. Caesalmin C is a cassane-type diterpenoid abundant in Caesalpinia bonduc (Linn.) Roxb. In this study, we investigated the effect of caesalmin C on Aß-induced toxicity and possible mechanisms in the transgenic Caenorhabditis elegans AD model. Our results showed that caesalmin C significantly alleviated the Aß-induced paralysis phenotype in transgenic CL4176 strain C. elegans. Caesalmin C dramatically reduced the content of Aß monomers, oligomers, and deposited spots in AD C. elegans. In addition, mRNA levels of sod-3, gst-4, and rpt-3 were up-regulated, and mRNA levels of ace-1 were down-regulated in nematodes treated with caesalmin C. The results of the RNAi assay showed that the inhibitory effect of caesalmin C on the nematode paralysis phenotype required the DAF-16 signaling pathway, but not SKN-1 and HSF-1. Further evidence suggested that caesalmin C may also have the effect of inhibiting acetylcholinesterase (AchE) and upregulating proteasome activity. These findings suggest that caesalmin C delays the progression of AD in C. elegans via the DAF-16 signaling pathway and that it could be developed into a promising medication to treat AD.

Cryptotanshinone Alleviates Oxidative Stress and Reduces the Level of Abnormally Aggregated Protein in Caenorhabditis elegans AD Models.

Alzheimer's disease (AD) is one of the leading causes of dementia. As the first common neurodegenerative disease, there are no effective drugs that can reverse the progression. The present study is to report the anti-AD effect of cryptotanshinone (CTS), a natural product isolated from Salvia castanea. It is found that it can alleviate AD-like features associated with Aß1-42 toxicity in muscle cells as well as neuronal cells of Caenorhabditis elegans (C. elegans). Further studies showed that CTS reduced the level of reactive oxygen species (ROS) in nematodes, up-regulated the expression of sod-3, and enhanced superoxide dismutase activity. Cryptotanshinone reduced the level of Aß monomers and highly toxic oligomers in C. elegans while inhibiting the abnormal aggregation of polyglutamine protein. In addition, CTS upregulated the expression of hsp-16.2 and downregulated the expression of ace-2. These results suggested that CTS could alleviate oxidative stress and reduce the level of abnormally aggregated proteins and has the potential to be developed as an anti-AD drug candidate.

The Relationship Between Hormone Replacement Therapy and Risk of Kidney Cancer in Women: A Meta-Analysis.

Results from the epidemiologic studies on the relationship between hormone replacement therapy (HRT) and the risk of kidney cancer in women were not completely consistent. This meta-analysis aimed to evaluate the relationship between HRT and risk of kidney cancer in women. We performed a meta-analysis of observational studies to assess this association. The PubMed and Embase databases were searched from their inception to January 29, 2020, to identify relevant studies that fit the pre-stated inclusion criteria; reference lists from the retrieved articles were also been reviewed. Relative risks (RRs) with corresponding 95% CIs were extracted and combined using random effects models. Furthermore, dose-response, sensitivity analyses, publication bias, and subgroup analysis by study design, regional location, and exposure assessment method were conducted. Thirteen articles involving 6 cohort studies and 8 case-control studies were included in our meta-analysis. Overall, 4194 women were diagnosed with kidney cancer among 648 107 participants. The pooled RR for kidney cancer was 1.08 (95% CI: 0.96-1.22) in those who were administered HRT compared to those who had not. Subgroup analysis indicated the overall result was not influenced by study type, regional location, or adjusted variables. Dose-response analysis showed a nonlinear relationship between HRT and kidney cancer (P = .0021) and the risk of kidney cancer decreased by 15% to 28% with 12 to 18 years of HRT use. No evidence of publication bias was found (P for Egger =.111). Our meta-analysis showed that HRT use is inversely associated with kidney cancer risk in a dose-dependent fashion.

Isolation, Characterization, and Possible Anti-Alzheimer's Disease Activities of Bisabolane-Type Sesquiterpenoid Derivatives and Phenolics from the Rhizomes of Curcuma longa.

One new bisabolane-type sesquiterpenoid, together with four known bisabolane-type sesquiterpenoid derivatives and seven phenolics, was isolated from the rhizomes of Curcuma longa. Their structures were elucidated by extensive spectroscopic (IR, HR-ESI-MS, and NMR) data analysis. The possible anti-Alzheimer's disease (AD) activities of the isolated compounds were also evaluated using Caenorhabditis elegans AD pathological model, and 1ß-hydroxybisabola-2,10-dien-4-one had the highest possible anti-AD activity.

Anticonvulsive activity of duloxetine: A new choice for the epileptic patients with depression.

The aim of this study was to investigate the antiepileptic effects of duloxetine in the maximal electroshock test and convulsions induced by four compounds: Pentylenetetrazole, 3-mercaptopropionic acid, thiosemicarbazide, and bicuculline. Duloxetine exhibited moderate anticonvulsive activity with an ED50 (median effective dose) of 48.21 mg/kg in the maximal electroshock test in mice. The anticonvulsive action of duloxetine was also confirmed in chemical-induced seizure tests, where this drug decreased tonic convulsions. Single administration of duloxetine (6.25-25 mg/kg) significantly increased the anticonvulsant effects of valproate, carbamazepine, and oxcarbazepine in the maximal electroshock test. Furthermore, pretreatment with thiosemicarbazide (an inhibitor of GABA synthesis enzyme) significantly increased the ED50 of duloxetine, suggesting the GABAergic system may contribute to the anticonvulsive action of duloxetine. These results support the use of duloxetine in the treatment of coexisting depression and epilepsy.

[Study of Kinase Inhibitor WP1066 on the STAT3/JAK2 of Prostate Stromal Cells].

OBJECTIVE: To study the role of JAK2 signaling pathway in prostate stromal cells and the effect of inhibitor WP1066 on its expression. METHODS: The phosphorylation of JAK2 and STAT3 in prostate tissues of patients with benign prostatic hyperplasia (BHP) (n=4) and severe histological prostatitis (HP) plus BPH (n=4) was tested by using Western blot to verify the activation of their mediated signaling pathway. Kinase inhibitor WP1066 was added to prostate stromal cells to detect inhibition of the JAK2 and STAT3 activation launched by IL-6. RESULTS: JAK2 phosphorylation level (pJAK2) was significantly increased in the patients with severe HP plus BPH,and the expression of JAK2 or STAT3 was not decreased in WP1066 treatment cells. However,neither phosphorylation in JAK2 nor STAT3 was able to be detected in the cells treated with WP1066 or WP1066+IL-6,indicating that the signaling pathway of JAK2-STAT3 was inhibited. CONCLUSION: JAK/STAT signaling pathway is activated in patients with severe HP plus BPH , but could be inhibited by WP1066.

[Topical application of clobetasol propionate cream in the treatment of phimosis in prepubertal children: A report of 237cases].

OBJECTIVE: To investigate the clinical effect of 0.02% clobetasol propionate cream (CPC) on phimosis in prepubertal children. METHODS: We retrospectively analyzed the clinical data about 237 prepubertal children with phimosis present at the Outpatient Department from June 2012 to December 2015. The patients were aged 2－14 (mean 8.6) years, all treated by topical application of 0.02% CPC to the narrowed opening and adhered part of the foreskin twice a day, in the morning and evening respectively. At the time of CPC application, the foreskin was slightly retracted. We evaluated the therapeutic effect every week from the end of the first week of treatment. RESULTS: Totally, 233 of the patients completed the 8-week treatment, of whom 181 (77.68%) showed full retraction of the foreskin, 28 (12.01%) experienced improvement (disappearance of the phimotic ring), and 24 (10.30%) failed to respond, with a total effectiveness rate of 89.70%. No significant local or systemic adverse reactions were observed during the treatment. CONCLUSIONS: Topical application of 0.02% Clobetasol Propionate Cream is a safe, effective, painless, and inexpensive option for the treatment of phimosis in prepubertal chilodren.

MiR-181b sensitizes glioma cells to teniposide by targeting MDM2.

BACKGROUND: Although the incidence of glioma is relatively low, it is the most malignant tumor of the central nervous system. The prognosis of high-grade glioma patient is very poor due to the difficulties in complete resection and resistance to radio-/chemotherapy. Therefore, it is worth investigating the molecular mechanisms involved in glioma drug resistance. MicroRNAs have been found to play important roles in tumor progression and drug resistance. Our previous work showed that miR-181b is involved in the regulation of temozolomide resistance. In the current study, we investigated whether miR-181b also plays a role in antagonizing the effect of teniposide. METHODS: MiR-181b expression was measured in 90 glioma patient tissues and its relationship to prognosis of these patients was analyzed. Cell sensitivity to teniposide was tested in 48 primary cultured glioma samples. Then miR-181b stably overexpressed U87 cells were generated. The candidate genes of miR-181b from our previous study were reanalyzed, and the interaction between miR-181b and target gene MDM2 was confirmed by dual luciferase assay. Cell sensitivity to teniposide was detected on miR-181b over expressed and MDM2 down regulated cells. RESULTS: Our data confirmed the low expression levels of miR-181b in high-grade glioma tissues, which is related to teniposide resistance in primary cultured glioma cells. Overexpression of miR-181b increased glioma cell sensitivity to teniposide. Through target gene prediction, we found that MDM2 is a candidate target of miR-181b. MDM2 knockdown mimicked the sensitization effect of miR-181b. Further study revealed that miR-181b binds to the 3'-UTR region of MDM2 leading to the decrease in MDM2 levels and subsequent increase in teniposide sensitivity. Partial restoration of MDM2 attenuated the sensitivity enhancement by miR-181b. CONCLUSIONS: MiR-181b is an important positive regulator on glioma cell sensitivity to teniposide. It confers glioma cell sensitivity to teniposide through binding to the 3'-UTR region of MDM2 leading to its reduced expression. Our findings not only reveal the novel mechanism involved in teniposide resistance, but also shed light on the optimization of glioma treatment in the future.

Malignant melanoma of the penis and urethra: one case report.

We present a case of a patient with malignant melanoma of the glans penis and urethra, which was found in a 53-year-old man with nonhealing ulcerative penile lesion and bilateral, clinically palpable inguinal lymphadenopathies at diagnosis. A diagnostic biopsy showed the characteristics of a melanoma. We treated the patient with total penectomy and bilateral inguinal lymph node dissection. After surgery, chemotherapy with bleomycin, vincristine and cisplatin and immunotherapy with thymosin injection were started. No recurrence or metastasis occurred during the 3 years after the operation. Melanoma of the penis is very rare, and early diagnosis is important because the patient prognosis is very poor.

[The role of actigraphy in monitoring sleep and sleep disorders].

The use of actigraphy, which can be used to estimate sleep-wake patterns from activity levels, has become common in sleep research. Actigraphy is a simple, cost-effective and non-invasive method for healthcare providers and researchers to assess patients sleep quality and screen for potential sleep disorders in recent years. But, there is no wide recognition and application of actigraphy in China up till now. This review summarized the application of actigraphy in evaluation of sleep and diagnosis of sleep disorders.

[Histological effects of unilateral spermatic cord torsion without removal of the ipsilateral necrotic testis on the contralateral testis in rats].

OBJECTIVE: To investigate the protective effect of retarded removal of the unilateral necrotic testis after long-time (> 24 h) spermatic cord torsion on the contralateral testis in rats. METHODS: Thirty-three male SD rats aged 21 -42 days were divided into a sham-operation group (n = 11), a torsion-reservation group (n = 12) and a torsion-orchiectomy group (n = 10). The rats of the sham-operation group received dartos pouch orchidopexy on the left testis, while those of the latter two groups underwent 720 degrees unilateral spermatic cord torsion on the left side. Ninety-six hours later, the rats of the torsion-reservation group received detorsion with the ipsilateral testis preserved, while those of the torsion-orchiectomy group underwent orchiectomy. Three months after operation, blood samples were obtained from the rats for measurement of serum testosterone and antisperm antibodies by ELISA, and meanwhile testes and epididymides were harvested for determination of the volumes of various structures and the diameter of seminiferous tubules with stereological methods. RESULTS: There were no significant differences in the level of serum testosterone among the three groups. Anti-sperm antibody positive was found in only 1 animal in the torsion-reservation group. The Leydig cell nuclei in the contralateral testis appeared larger in the torsion groups than in the sham-operation group. Marked morphological changes were observed in 1, 3 and 0 of the animals in the sham-operation, torsion-reservation and torsion-orchiectomy group, respectively, mainly including atrophy of seminiferous tubules and reduced number of spermatogenic cells. The volume of the contralateral testis was increased by 19% and 21% in the torsion-reservation and torsion-orchiectomy group, respectively, in comparison with that in the sham-operation group (P < 0.05). No significant differences were observed in the volume of seminiferous tubules of the contralateral testis among the sham-operation, torsion-reservation and torsion-orchiectomy groups ([1.15 +/- 0.07], [1.30 +/- 0.04] and [1.35 +/- 0.05] cm3). The volume of the interstitial tissue was significantly increased in the latter two groups ([0.36 +/- 0.02 and 0.34 +/- 0.03] cm3) as compared with the former ([0.25 +/- 0.02] cm3) (P < 0.05). The diameters of the seminiferous tubules exhibited no significant differences among the three groups ([226.00 +/- 7.00], [223.00 +/- 6.00] and [221.00 +/- 3.0] microm). CONCLUSION: Long-time unilateral spermatic cord torsion may result in compensatory hypertrophy of the contralateral testis, and orchiectomy does not significantly affect the histology of the contralateral testis and epididymis.

Lithium Polyacrylate as Lithium and Carbon Source in the Synthesis of Li3 VO4 for High-Rate and Long-Life Li-Ion Batteries.

Li3 VO4 is a promising anode material for use in lithium-ion batteries, however, the conventional synthesis methods for Li3 VO4 anodes involve the separate use of lithium and carbon sources, resulting in inefficient contact and low crystalline quality. Herein, lithium polyacrylate (LiPAA) was utilized as a dual-functional source and an in-situ polymerization followed by a spray-drying method was employed to synthesize Li3 VO4 . LiPAA serves a dual purpose, acting as both a lithium source to improve the crystal process and a carbon source to confine the particle size within a desired volume during high-temperature treatment. Additionally, the in-situ synthesis of a porous carbon decorating skeleton prevents the growth and agglomeration of Li3 VO4 particles and provides abundant ion/electron diffusion channels and contact areas. Based on the synthesis route and the constructed primary-secondary structure, the Li3 VO4 anodes obtained in this study exhibit an impressive capacity of 596.2 mAh g-1 . Moreover, they demonstrate enhanced rate performance over 600 cycles during 10 periods of rate testing, as well as a remarkably long lifespan of 5000 cycles at high currents. The utilization of LiPAA as a dual-functional source represents a broad approach that holds great potential for future research on high-performance electrodes requiring both lithium and carbon sources.

Effects of Varying Levels of Wheat Bran Dietary Fiber on Growth Performance, Fiber Digestibility and Gut Microbiota in Erhualian and Large White Pigs.

To evaluate the tolerance of a high-fiber diet in Erhualian pigs (Er-HL), the present investigation systematically investigated the ramifications of varying wheat bran fiber levels, specified as total dietary fiber (TDF) values of 14.07%, 16.32%, 17.99%, and 18.85%, on growth performance, fiber digestibility and gut microbiota in Er-HL, large Large White pigs (L-LW, the same physiological stage as the Er-HL) and small Large White pigs (S-LW, the same body weight as the Er-HL). Our results revealed that fiber levels exerted no discernable impact on growth performance (average daily feed intake (ADFI), and average daily gain (ADG)) of Er-HL (p > 0.05). Conversely, L-LW exhibited a decrease in ADFI and ADG with increasing fiber levels (p < 0.05). Notably, the apparent total tract digestibility (ATTD) of various fiber components, including neutral detergent fiber (NDF), acid detergent fiber (ADF), hemicellulose, TDF and insoluble dietary fiber (IDF), in Er-HL were significantly higher than those in S-LW and L-LW irrespective of diets (p < 0.05). The ATTD of cellulose and hemicellulose in Er-HL significantly decreased with increasing fiber levels (p < 0.05), yet remained statistically indifferent when comparing the 7%-wheat-bran-replaced diet (7% WRB, TDF 16.32%) to the basal diet (TDF 14.07%) (p > 0.05). The cecal microbiota of Er-HL had higher richness estimators (Chao1 and ACE) than those of S-LW and L-LW irrespective of diets (p < 0.01). Breed serves as a pivotal determinant in shaping swine gut microbiota. Thirteen genera were selected as the key bacteria related to high fiber digestibility of Er-HL. Further functional examination of these key genera elucidated an enrichment of pathways pertinent to carbohydrate metabolism in Er-HL samples compared with S-LW and L-LW samples. In summary, Er-HL exhibited high-fiber tolerance both in terms of growth performance and fiber digestibility compared with Large White pigs. Specifically, the ATTD of NDF, ADF, hemicellulose, IDF and TDF were significantly higher in Er-HL compared with L-LW and S-LW, irrespective of diets. Fiber level exerted no discernable impact on growth performance (ADFI, ADG) and the ATTD of fiber (NDF, ADF, IDF and TDF) in Er-HL. The optimum fiber level of the Er-HL was identified as 7% WRB (TDF 16.32%). Thirteen genera were ascertained to significantly contribute to high fiber digestibility of Er-HL, correlating with an enhancement of carbohydrate metabolism pathways.

Hierarchical Self-Assembly Strategy for Scalable Synthesis of Li3VO4/N Doped C Nanosheets for High-Rate Li-Ion Storage.

While the comprehensive merits of high safety and high capacity make Li3VO4 (LVO) a potential anode material for lithium-ion batteries, the practical application of LVO was severely impeded by the unfavorable high-rate capability and unscalable preparation. Here, LVO/N doped C nanosheets (LVO@NC NSs) assembled from primary LVO@NC nanoparticles are prepared via a scalable and concise spray drying approach. The 2D morphology and the interconnected LVO@NC constituents endow the LVO@NC NSs with continuously excellent reaction activity, leading to prominent rate performance. When cycling at 0.2 A g-1, the obtained LVO@NC NSs exhibit a high charge capacity of 628.4 mAh g-1 after 300 cycles, showing little improvement compared with the initial charge capacity. After 9 periods of rate testing ranging from 0.1 to 6.0 A g-1 for 460 cycles, a high charge capacity of 610.3 mAh g-1 remains. It also exhibits an outstanding long lifespan at the charge/discharge currents of 3.0/6.0 A g-1, delivering a high charge capacity of 277.0 mAh g-1 in the 5000th cycle. The scalable and concise preparation as well as the enhanced high-rate capability of the LVO@NC NSs make them hold great promise as an anode candidate for high-power lithium-ion storage devices.

Comparison of the effectiveness and safety of robotic-assisted and laparoscopic in adrenalectomy: A systematic review and meta-analysis.

OBJECTIVE: To compare the safety and effectiveness of robot-assisted adrenalectomy (RA) and laparoscopic adrenalectomy (LA). METHODS: We performed a systematic review and cumulative meta-analysis of the primary outcomes of interest according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the Methodological Quality of Systematic Reviews) Guidelines. Five databases, including Medline, PubMed, Cochrane Library, Scopus, and Web of Science, were systematically searched. The search timeframe was set from the creation of the database to December 2021. RESULTS: There were 26 studies including 2985 patients. Our study found that the robotic technique was superior to conventional laparoscopy for estimated blood loss (WMD = -18.25, 95% CI [-27.85, -8.65], P < 0.01), length of stay (WMD = -0.45, 95% CI [-0.57, -0.33], P < 0.01), and conversion to open (OR = 0.31, 95% CI [0.12, 0.78], P = 0.01), while complications and readmissions were comparable. Interestingly, there was no difference in operative time between the two surgical modalities, but subgroup analysis found that the retroperitoneal route robotic technique took longer (WMD = 14.64, 95% CI [0.04, 29.24], P < 0.05), whereas the study of the mixed surgical modality (RA versus LA with mixed transabdominal and retroperitoneal surgical routes) found that the robot required less time (WMD = -12.29, 95% CI [-22.86, -1.72], P < 0.05). For pheochromocytoma, RA was superior to LA in terms of length of stay (WMD = -0.49, 95% CI [-0.83, -0.15], P < 0.01), with no difference in other indicators. CONCLUSION: robotic-assisted adrenalectomy is a superior technique to conventional laparoscopy in managing adrenal tumors, even in the case of a specific adrenal tumor - pheochromocytoma.

Genome-Wide Association Study and FST Analysis Reveal Four Quantitative Trait Loci and Six Candidate Genes for Meat Color in Pigs.

Meat color is the primary criterion by which consumers evaluate meat quality. However, there are a few candidate genes and molecular markers of meat color that were reported for pig molecular breeding. The purpose of the present study is to identify the candidate genes affecting meat color and provide the theoretical basis for meat color molecular breeding. A total of 306 Suhuai pigs were slaughtered, and meat color was evaluated at 45 min and 24 h after slaughter by CIELAB color space. All individuals were genotyped using GeneSeek GGP-Porcine 80K SNP BeadChip. The genomic estimated breeding values (GEBVs), heritability, and genetic correlation of meat color were calculated by DMU software. The genome-wide association studies (GWASs) and the fixation index (FST) tests were performed to identify SNPs related to meat color, and the candidate genes within 1 Mb upstream and downstream of significant SNPs were screened by functional enrichment analysis. The heritability of L* 45 min, L* 24 h, a* 45 min, a* 24 h, b* 45 min, and b* 24 h was 0.20, 0.16, 0.30, 0.13, 0.29, and 0.22, respectively. The genetic correlation between a* (a* 45 min and a* 24 h) and L* (L* 45 min and L* 24 h) is strong, whereas the genetic correlation between b* 45 min and b* 24 h is weak. Forty-nine significant SNPs associated with meat color were identified through GWAS and FST tests. Among these SNPs, 34 SNPs were associated with L* 45 min within a 5-Mb region on Sus scrofa chromosome 11 (SSC11); 22 SNPs were associated with a* 45 min within a 14.72-Mb region on SSC16; six SNPs were associated with b* 45 min within a 4.22-Mb region on SSC13; 11 SNPs were associated with b* 24 h within a 2.12-Mb region on SSC3. These regions did not overlap with meat color-associated QTLs reported previously. Moreover, six candidate genes (HOMER1, PIK3CG, PIK3CA, VCAN, FABP3, and FKBP1B), functionally related to muscle development, phosphatidylinositol phosphorylation, and lipid binding, were detected around these significant SNPs. Taken together, our results provide a set of potential molecular markers for the genetic improvement of meat color in pigs.

Caesalpinbondin A, a Novel Diterpenoid Lactone With an Unprecedented Carbon Skeleton from the Seeds of Caesalpinia bonduc.

One novel diterpenoid lactone named caesalpinbondin A (1) that possesses an unprecedented tetracyclic ring system in which a 6/6/5-fused tricyclic ring and a 4,5-dimethyldihydrofuran-2(3H)-one were connected by a C-C single bond comprising a 5-(naphtho [2,3-b]furan-7-yl)dihydrofuran-2(3H)-one moiety was isolated from the seeds of Caesalpinia bonduc. Its chemical structure was established by extensive spectroscopic methods, and its absolute configuration was further determined by single-crystal X-ray diffraction analysis and electronic circular dichroism calculation. The biological evaluation suggested that compound 1 demonstrated potent anti-Alzheimer's disease (AD) bioactivity, which could delay paralysis of transgenic AD Caenorhabditis elegans. A possible biogenetic pathway of 1 was also proposed.

Genome-wide association study and genomic prediction for intramuscular fat content in Suhuai pigs using imputed whole-genome sequencing data.

Integrating the single-nucleotide polymorphisms (SNPs) significantly affecting target traits from imputed whole-genome sequencing (iWGS) data into the genomic prediction (GP) model is an economic, efficient, and feasible strategy to improve prediction accuracy. The objective was to dissect the genetic architecture of intramuscular fat content (IFC) by genome wide association studies (GWAS) and to investigate the accuracy of GP based on pedigree-based BLUP (PBLUP) model, genomic best linear unbiased prediction (GBLUP) models and Bayesian mixture (BayesMix) models under different strategies. A total of 482 Suhuai pigs were genotyped using an 80 K SNP chip. Furthermore, 30 key samples were selected for resequencing and were used as a reference panel to impute the 80 K chip data to the WGS dataset. The 80 K data and iWGS data were used to perform GWAS and test GP accuracies under different scenarios. GWAS results revealed that there were four major regions affecting IFC. Two important functional candidate genes were found in the two most significant regions, including protein kinase C epsilon (PRKCE) and myosin light chain 2 (MYL2). The results of the predictions showed that the PBLUP model had the lowest reliability (0.096 ± 0.032). The reliability (0.229 ± 0.035) was improved by replacing pedigree information with 80 K chip data. Compared with using 80 K SNPs alone, pruning iWGS SNPs with the R-squared cutoff of linkage disequilibrium (0.55) led to a slight improvement (0.006), adding significant iWGS SNPs led to an improvement of reliability by 0.050 when using a one-component GBLUP, a further increase of 0.033 when using a two-component GBLUP model. For BayesMix models, compared with using 80 K SNPs alone, adding additional significant iWGS SNPs into one- or two-component BayesMix models led to improvements of reliabilities for IFC by 0.040 and 0.089, respectively. Our results may facilitate further identification of causal genes for IFC and may be beneficial for the improvement of IFC in pig breeding programs.