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Abstract Background C-C chemokine receptor 5 (CCR5) has recently been recognized as an underlying therapeutic target for various malignancies. However, the association of CCR5 with prognosis in the head and neck squamous cell carcinoma (HNSC) patients and tumor-infiltrating lymphocytes (TILs) is unclear. Methods In the current experiment, methods such as the Tumor Immune Estimation Resource Analysis (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier plotter Analysis were used to comprehensively evaluate the expression of CCR5 in human various malignancies and the clinical prognosis in HNSC patients. Subsequently, we used the TIMER database and the TISIDB platform to investigate the correlation between CCR5 expression levels and immune cell infiltration in the HNSC tumor microenvironment. Furthermore, immunomodulatory and chemokine profiling were performed using the TISIDB platform to analyse the correlation between CCR5 expression levels and immunomodulation in HNSC patients. Results We found that CCR5 expression in HNSC tumor tissues was significantly upregulated than in normal tissues. In HNSC, patients with high CCR5 expression levels had worse overall survival (OS, HR = 0.59, p = 0.00015) and worse recurrence-free survival (RFS, HR = 3.27, p = 0.00098). Upregulation of CCR5 expression is closely associated with immunomodulators, chemokines, and infiltrating levels of CD4+ T cells, neutrophils, macrophages, and myeloid dendritic cells. Furthermore, upregulated CCR5 was significantly associated with different immune markers in the immune cell subsets of HNSC. Conclusions High expression of CCR5 plays an important prognostic role in HNSC patients and may serve as a prognostic biomarker correlated with immune infiltration, and further studies are still needed to investigate therapeutic targeting HNSC patients in the future.

Sinomenine, an isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, has been extensively studied for its derivatives as bioactive agents. This review concentrates on the research advancements in the biological activities and action mechanisms of sinomenine-related compounds until November 2023. The findings indicate a broad spectrum of pharmacological effects, including antitumor, anti-inflammation, neuroprotection, and immunosuppressive properties. These compounds are notably effective against breast, lung, liver, and prostate cancers, exhibiting IC50 values of approximately 121.4 nM against PC-3 and DU-145 cells, primarily through the PI3K/Akt/mTOR, NF-κB, MAPK, and JAK/STAT signaling pathways. Additionally, they manifest anti-inflammatory and analgesic effects predominantly via the NF-κB, MAPK, and Nrf2 signaling pathways. Utilized in treating rheumatic arthritis, these alkaloids also play a significant role in cardiovascular and cerebrovascular protection, as well as organ protection through the NF-κB, Nrf2, MAPK, and PI3K/Akt/mTOR signaling pathways. This review concludes with perspectives and insights on this topic, highlighting the potential of sinomenine-related compounds in clinical applications and the development of medications derived from natural products.

ObjectiveRecently, short-term spinal cord stimulation (st-SCS) has been used in neurorehabilitation and consciousness recovery. However, little is known about its effects on primary brainstem hemorrhage (PBSH)-induced disorders of consciousness (DOC). In this study, we examined the therapeutic effects of st-SCS in patients with PBSH-induced DOC.MethodsFourteen patients received a 2-week st-SCS therapy. Each patient's state of consciousness was evaluated using the Coma Recovery Scale-Revised (CRS-R). CRS-R evaluation scores were recorded at the baseline (before SCS implantation) and 14 days later.ResultsOver 70% (10/14) of the patients (CRS-R score increased to ≥2 points) responded to the SCS stimulation after 14 days of st-SCS treatment. All items included in the CRS-R exhibited a significant increase post-treatment compared with pretreatment. After 2 weeks of st-SCS treatment, seven patients showed diagnostic improvement, resulting in a 50% (7/14) overall effective rate. Approximately 75% (3/4) of patients with minimally conscious state plus (MCS+) improved to emergence from MCS (eMCS), and 50% (1/2) of patients with vegetative state or unresponsive wakefulness syndrome (VS/UWS) improved to MCS+.ConclusionIn PBSH-induced DOC, st-SCS is a safe and effective treatment. The clinical behavior of the patients improved significantly following the st-SCS intervention, and their CRS-R scores markedly increased. This was most effective for MCS+.

Abstract Laiwu pigs are a Chinese indigenous breed that is renowned for its exceptionally high intramuscular fat content (average greater than 6%), providing an excellent genetic resource for the genetic improvement of meat quality of modern commercial pigs. To uncover genetic diversity, population structure, signature of selection, and potential exotic introgression in this breed, we sampled 238 Laiwu pigs from a state‐supported conservation population and genotyped these individuals using GeneSeek 80K SNP BeadChip. We then conducted in‐depth population genetics analyses for the Laiwu pig in a context of 1,116 pigs from 42 Eurasian diverse breeds. First, we show that the current Laiwu population has more abundant genetic diversity than the population of 18 years ago likely due to gene flow from European commercial breeds. Both neighbor‐joining (NJ) and principal component analyses indicate the introgression of European haplotypes into Laiwu pigs. The admixture analysis reveals that an average 26.66% of Laiwu genetic components are of European origin. Then, we assigned the tested individuals to different families according to their clustering patterns in the NJ tree and proposed a family‐based conservation strategy to reduce the risk of inbreeding depression in Laiwu pigs. Next, we explored three statistics (ROH and iHS and EigenGWAS) to identify a list of candidate genes for fat deposition, reproduction, and growth in Laiwu pigs. Last, we detected a strong signature of introgression from European pigs into Laiwu pigs at the GPC6 locus that regulates the growth of developing long bones. Further association analyses indicate that the introgressed GPC6 haplotype likely contributed to the improvement of growth performance in Laiwu pigs. Altogether, this study not only benefits the better conservation of the Laiwu pig, but also advances our knowledge of the poorly understood effect of human‐mediated introgression on phenotypic traits in Chinese indigenous pigs.

Runs of homozygosity (ROH) and heterozygosity (ROHet) are windows into population demographic history and adaptive evolution. Numerous studies have shown that deleterious mutations are enriched in the ROH of humans, pigs, cattle, and chickens. However, the relationship of deleterious variants to ROH and the pattern of ROHet in goats have been largely understudied. Here, 240 Guangfeng and Ganxi goats from Jiangxi Province, China, were genotyped using the Illumina GoatSNP50 BeadChip and genome-wide ROH, ROHet, and genetic load analyses were performed in the context of 32 global goat breeds. The classes with the highest percentage of ROH and ROHet were 0.5–2 Mb and 0.5–1 Mb, respectively. The results of inbreeding coefficients (based on SNP and ROH) and ROHet measurements showed that Guangfeng goats had higher genetic variability than most Chinese goats, while Ganxi goats had a high degree of inbreeding, even exceeding that of commercial goat breeds. Next, the predicted damaging homozygotes were more enriched in long ROHs, especially in Guangfeng goats. Therefore, we suggest that information on damaging alleles should also be incorporated into the design of breeding and conservation programs. A list of genes related to fecundity, growth, and environmental adaptation were identified in the ROH hotspots of two Jiangxi goats. A sense-related ROH hotspot (chromosome 12: 50.55–50.81 Mb) was shared across global goat breeds and may have undergone selection prior to goat domestication. Furthermore, an identical ROHet hotspot (chromosome 1: 132.21–132.54 Mb) containing two genes associated with embryonic development (STAG1 and PCCB) was detected in domestic goat breeds worldwide. Tajima’s D and BetaScan2 statistics indicated that this region may be caused by long-term balancing selection. These findings not only provide guidance for the design of conservation strategies for Jiangxi goat breeds but also enrich our understanding of the adaptive evolution of goats.

Age at first egg (AFE) and egg number (EN) are economically important traits related to egg production, as they directly influence the benefits of the poultry industry, but the molecular genetic research that affects those traits in laying ducks is still sparse. Our objective was to identify the genomic regions and candidate genes associated with AFE, egg production at 43 weeks (EP43w), and egg production at 66 weeks (EP66w) in a Shaoxing duck population using genome-wide association studies (GWASs) and haplotype-sharing analysis. Single-nucleotide polymorphism (SNP)-based genetic parameter estimates showed that the heritability was 0.15, 0.20, and 0.22 for AFE, EP43w, and EP66w, respectively. Subsequently, three univariate GWASs for AFE, EP43w, and EP66w were carried out independently. Twenty-four SNPs located on chromosome 25 within a 0.01-Mb region that spans from 4.511 to 4.521 Mb were associated with AFE. There are two CIs that affect EP43w, i.e., twenty-five SNPs were in strong linkage disequilibrium region spanning from 3.186 to 3.247 Mb on chromosome 25, a region spanning from 4.442 to 4.446 Mb on chromosome 25, and two interesting genes, ACAD8 and THYN1, that may affect EP43w in laying ducks. There are also two CIs that affect EP66w, i.e., a 2.412-Mb region that spans from 127.497 to 129.910 Mb on chromosome 2 and a 0.355-Mb region that spans from 4.481 to 4.837 Mb on chromosome 29, and CA2 and GAMT may be the putative candidate genes. Our study also found some haplotypes significantly associated with these three traits based on haplotype-sharing analysis. Overall, this study was the first publication of GWAS on egg production in laying ducks, and our findings will be helpful to provide some candidate genes and haplotypes to improve egg production performance based on breeding in laying duck. Additionally, we learned from a method called bootstrap test to verify the reliability of a GWAS with small experimental samples that users can access at https://github.com/xuwenwu24/Bootstrap-test.

Objective Three genome-wide association studies (GWAS) and a meta-analysis of GWAS were conducted to explore the genetic mechanisms underlying variation in pig teat number. Methods We performed three GWAS and a meta-analysis for teat number on three pig populations, including a White Duroc×Erhualian F2 resource population (n = 1,743), a Chinese Erhualian pig population (n = 320) and a Chinese Sutai pig population (n = 383). Results We detected 24 single nucleotide polymorphisms (SNPs) that surpassed the genome-wide significant level on Sus Scrofa chromosomes (SSC) 1, 7, and 12 in the F2 resource population, corresponding to four loci for pig teat number. We highlighted vertnin (VRTN) and lysine demethylase 6B (KDM6B) as two interesting candidate genes at the loci on SSC7 and SSC12. No significant associated SNPs were identified in the meta-analysis of GWAS. Conclusion The results verified the complex genetic architecture of pig teat number. The causative variants for teat number may be different in the three populations

The dihedral angle between the planes of the two aromatic rings of the title compound, C16H13N3S, is 56.7 (3)°. The crystal packing is stabilized by intermolecular N—H...N hydrogen bonds, which link the molecules into chains along [11-1].

In the title compound, C21H21N3OS·C3H7NO, the carbonitrile molecule is built up of two fused six-membered rings and one six-membered ring linked through a spiro C atom. The 1,3-diaza ring adopts an envelope conformation and the cyclohexane ring adopts a chair conformation. The dihedral angle between the aromatic rings is 46.7 (3)°. In the crystal, the components are linked by N—H...O hydrogen bonds.

The title compound, C21H21N3O, was obtained by cyclocondensation of 3-amino-5-methyl-[1,1′-biphenyl]-2,4-dicarbonitrile with cyclohexanone. The six-membered 1,3-diaza ring assumes an envelope conformation [with the flap atom displaced by 0.511 (7) Å from the plane through the other ring atoms] and the cyclohexane ring displays a chair conformation. The dihedral angle between the aromatic rings is 42.61 (7)°.In the crystal, the molecules form hydrogen-bonded bands along [011].

The title compound, C11H13N2O, was obtained by cyclocondensation of 2-aminopyridine-3-carbonitrile with cyclopentanone. The molecule is built up from two fused six-membered rings and one five-membered ring linked through a spiro C atom. Both the pyrimidine and the cyclopentane rings adopt envelope conformations. In the crystal structure, molecules are linked by intermolecular N—H...O hydrogen bonds.

Disorders of consciousness (DOC) is a state in which consciousness is affected by brain injuries, leading to dysfunction in vigilance, awareness, and behavior. DOC encompasses coma, vegetative state, and minimally conscious state based on neurobehavioral function. Currently, DOC is one of the most common neurological disorders with a rapidly increasing incidence worldwide. Therefore, DOC not only impacts the lives of individuals and their families but is also becoming a serious public health threat. Repetitive transcranial magnetic stimulation (rTMS) can stimulate electrical activity using a pulsed magnetic field in the brain, with great value in the treatment of chronic pain, neurological diseases, and mental illnesses. However, the clinical application of rTMS in patients with DOC is debatable. Herein, we report the recent main findings of the clinical therapeutics of rTMS for DOC, including its efficacy and possible mechanisms. In addition, we discuss the potential key parameters (timing, location, frequency, strength, and secession of rTMS applications) that affect the therapeutic efficiency of rTMS in patients with DOC. This review may help develop clinical guidelines for the therapeutic application of rTMS in DOC. [ABSTRACT FROM AUTHOR]

A total of 26 mice were observed with vaginal septa and 10 of them progressively developed into vaginal atresia. Among these vaginal atresia mice, 6 mice eventually suffered from uterus hydrometrocolpos syndrome (HMCPS) and polycystic ovary syndrome (PCOS) and the others were cured with surgical intervention once the vaginal orifices were found closed. Imaging and pathological observation showed that vaginal atresia led to cervix's lipoid secretion and uterine effusion. Moreover, Serum biochemical examination and ELISA test revealed significantly dramatic drop (about 50%) in blood triglycerides (P<0.01) and double increase in aromatase (P<0.01) in vaginal atresia mice. These findings give gained variable insight into further studies and provide vital guide for therapy on vaginal atresia. [ABSTRACT FROM AUTHOR]

An energy harvesting bracelet (EHB) based on two mutually exclusive circular motion permanent magnetic movers is demonstrated, which is able to capture energy through the natural motions of the wearer's wrist. The EHB can transform the translational motion in any orientation except the axial into the rotational motion of the movers, which passes through four coil transducers and induces significantly large electro-motive forces across the coils. A prototype EHB is shown to produce power that can charge a capacitor with 470 μF 25V up to more than 0.81V during at most 132 ms from any single excitations. [ABSTRACT FROM AUTHOR]

Hair provides thermal regulation for mammals and protects the skin from wounds, bites and ultraviolet (UV) radiation, and is important in adaptation to volatile environments. Pigs in nature are divided into hairy and hairless, which provide a good model for deciphering the molecular mechanisms of hairlessness. We conducted a genomic scan for genetically differentiated regions between hairy and hairless pigs using 60K SNP data, with the aim to better understand the genetic basis for the hairless phenotype in pigs. A total of 38405 SNPs in 498 animals from 36 diverse breeds were used to detect genomic signatures for pig hairlessness by estimating between-population (FST) values. Seven diversifying signatures between Yucatan hairless pig and hairy pigs were identified on pig chromosomes (SSC) 1, 3, 7, 8, 10, 11 and 16, and the biological functions of two notable genes, RGS17 and RB1, were revealed. When Mexican hairless pigs were contrasted with hairypigs, strong signatures were detected on SSC1 and SSC10, which harbor two functionally plausible genes, REV3L and BAMBI. KEGG pathway analysis showed a subset of overrepresented genes involved in the T cell receptor signaling pathway, MAPK signaling pathway and the tight junction pathways. All of these pathways may be important in local adaptability of hairless pigs. The potential mechanisms underlying the hairless phenotype in pigs are reported for the first time. RB1 and BAMBI are interesting candidate genes for the hairless phenotype in Yucatan hairless and Mexico hairless pigs, respectively. RGS17, REV3L, ICOS and RASGRP1 as well as other genes involved in the MAPK and T cell receptor signaling pathways may be important in environmental adaption by improved tolerance to UV damage in hairless pigs. These findings improve our understanding of the genetic basis for inherited hairlessness in pigs.