Relevance of PUFA-derived metabolites in seminal plasma to male infertility

AimThis study aims to investigate the biological effects of polyunsaturated fatty acid (PUFA)-derived metabolites in seminal plasma on male fertility and to evaluate the potential of PUFA as a biomarker for normozoospermic male infertility.MethodsFrom September 2011 to April 2012, We collected semen samples from 564 men aged 18 to 50 years old (mean=32.28 years old)ch., residing in the Sandu County, Guizhou Province, China. The donors included 376 men with normozoospermia (fertile: n=267; infertile: n=109) and 188 men with oligoasthenozoospermia (fertile: n=121; infertile: n=67). The samples thus obtained were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to detect the levels of PUFA-derived metabolites in April 2013. Data were analyzed from December 1, 2020, to May 15, 2022.ResultsOur analysis of propensity score-matched cohorts revealed that the concentrations of 9/26 and 7/26 metabolites differed significantly between fertile and infertile men with normozoospermia and oligoasthenozoospermia, respectively (FDR < 0.05). In men with normozoospermia, higher levels of 7(R)-MaR1 (HR: 0.4 (95% CI [0.24, 0.64]) and 11,12-DHET (0.36 (95% CI [0.21, 0.58]) were significantly associated with a decreased risk of infertility, while higher levels of 17(S)-HDHA (HR: 2.32 (95% CI [1.44, 3.79]), LXA5 (HR: 8.38 (95% CI [4.81, 15.24]), 15d-PGJ2 (HR: 1.71 (95% CI [1.06, 2.76]), and PGJ2 (HR: 2.28 (95% CI [1.42, 3.7]) correlated with an increased risk of infertility. Our ROC model using the differentially expressed metabolites showed the value of the area under the curve to be 0.744.ConclusionThe PUFA-derived metabolites 7(R)-MaR1, 11,12-DHET, 17(S)-HDHA, LXA5, and PGJ2 might be considered as potential diagnostic biomarkers of infertility in normozoospermic men

Phosphoantigen/IL2 Expansion and Differentiation of Vγ2Vδ2 T Cells Increase Resistance to Tuberculosis in Nonhuman Primates

Dominant Vγ2Vδ2 T-cell subset exist only in primates, and recognize phosphoantigen from selected pathogens including M. tuberculosis(Mtb). In vivo function of Vγ2Vδ2 T cells in tuberculosis remains unknown. We conducted mechanistic studies to determine whether earlier expansion/differentiation of Vγ2Vδ2 T cells during Mtb infection could increase immune resistance to tuberculosis in macaques. Phosphoantigen/IL-2 administration specifically induced major expansion and pulmonary trafficking/accumulation of phosphoantigen-specific Vγ2Vδ2 T cells, significantly reduced Mtb burdens and attenuated tuberculosis lesions in lung tissues compared to saline/BSA or IL-2 controls. Expanded Vγ2Vδ2 T cells differentiated into multifunctional effector subpopulations capable of producing anti-TB cytokines IFNγ, perforin and granulysin, and co-producing perforin/granulysin in lung tissue. Mechanistically, perforin/granulysin-producing Vγ2Vδ2 T cells limited intracellular Mtb growth, and macaque granulysin had Mtb-bactericidal effect, and inhibited intracellular Mtb in presence of perforin. Furthermore, phosphoantigen/IL2-expanded Vγ2Vδ2 T effector cells produced IL-12, and their expansion/differentiation led to enhanced pulmonary responses of peptide-specific CD4+/CD8+ Th1-like cells. These results provide first in vivo evidence implicating that early expansion/differentiation of Vγ2Vδ2 T effector cells during Mtb infection increases resistance to tuberculosis. Thus, data support a rationale for conducting further studies of the γδ T-cell-targeted treatment of established TB, which might ultimately help explore single or adjunctive phosphoantigen expansion of Vγ2Vδ2 T-cell subset as intervention of MDR-tuberculosis or HIV-related tuberculosis

DR*W201/P65 Tetramer Visualization of Epitope-Specific CD4 T-Cell during M. tuberculosis Infection and Its Resting Memory Pool after BCG Vaccination

In vivo kinetics and frequencies of epitope-specific CD4 T cells in lymphoid compartments during M. tuberculosis infection and their resting memory pool after BCG vaccination remain unknown.Macaque DR*W201 tetramer loaded with Ag85B peptide 65 was developed to directly measure epitope-specific CD4 T cells in blood and tissues form macaques after M. tuberculosis infection or BCG vaccination via direct staining and tetramer-enriched approach. The tetramer-based enrichment approach showed that P65 epitope-specific CD4 T cells emerged at mean frequencies of approximately 500 and approximately 4500 per 10(7) PBL at days 28 and 42, respectively, and at day 63 increased further to approximately 22,000/10(7) PBL after M. tuberculosis infection. Direct tetramer staining showed that the tetramer-bound P65-specific T cells constituted about 0.2-0.3% of CD4 T cells in PBL, lymph nodes, spleens, and lungs at day 63 post-infection. 10-fold expansion of these tetramer-bound epitope-specific CD4 T cells was seen after the P65 peptide stimulation of PBL and tissue lymphocytes. The tetramer-based enrichment approach detected BCG-elicited resting memory P65-specific CD4 T cells at a mean frequency of 2,700 per 10(7) PBL.Our work represents the first elucidation of in vivo kinetics and frequencies for tetramer-bound epitope-specific CD4 T cells in the blood, lymphoid tissues and lungs over times after M. tuberculosis infection, and BCG immunization

The inflammatory cytokine IL-6 induces FRA1 deacetylation promoting colorectal cancer stem-like properties

Colorectal cancer (CRC) has long been known for its tight association with chronic inflammation, thought to play a key role in tumor onset and malignant progression through the modulation of cancer stemness. However, the underlying molecular and cellular mechanisms are still largely elusive. Here we show that the IL-6/STAT3 inflammatory signaling axis induces the deacetylation of FRA1 at the Lys-116 residue located within its DNA-binding domain. The HDAC6 deacetylase underlies this key modification leading to the increase of FRA1 transcriptional activity, the subsequent transactivation of NANOG expression, and the acquisition of stem-like cellular features. As validated in a large (n = 123) CRC cohort, IL-6 secretion was invariably accompanied by increased FRA1 deacetylation at K116 and an overall increase in its protein levels, coincident with malignant progression and poor prognosis. Of note, combined treatment with the conventional cytotoxic drug 5-FU together with Tubastatin A, a HDAC6-specific inhibitor, resulted in a significant in vivo synergistic inhibitory effect on tumor growth through suppression of CRC stemness. Our results reveal a novel transcriptional and posttranslational regulatory cross-talk between inflammation and stemness signaling pathways that underlie self-renewal and maintenance of CRC stem cells and promote their malignant behavior. Combinatorial treatment aimed at the core regulatory mechanisms downstream of IL-6 may offer a novel promising approach for CRC treatment

An Inner- and Outer-Fed Dual-Arm Archimedean Spiral Antenna for Generating Multiple Orbital Angular Momentum Modes

Orbital angular momentum (OAM) beams have attracted great attention owing to their excellent performances in imaging and communication. In this paper, a dual-arm Archimedean spiral antenna (DASA) is proposed to generate multiple OAM states with positive and negative values by feeding at the inner and outer ends, respectively. The topological charge of radiated vortex waves is reconfigurable by tuning the operating frequency. Dual-mode OAM states are generated at different working frequencies (l = ±1 at 3 GHz, l = ±2 at 4 GHz, and l = ±3 at 4.8 GHz). Both the simulation and measurement results demonstrate that OAM beams can be generated effectively by the DASA. In addition, a conical cavity is used to increase the gain of the proposed DASA for more than 5 dBi in comparison to the traditional cylindrical cavity. Furthermore, the qualities of the generated OAM modes by the proposed DASA have been evaluated at different operating frequencies of 3 GHz, 4 GHz, and 4.8 GHz, respectively. The OAM modes purities of l = −1, −2, −3, 1, 2, and 3 are predominate with the proportion of about 81%, 70%, 74%, 78%, 77%, and 75%, respectively. Our results demonstrate that the proposed DASA has great potentials in OAM multiplexing communication systems

A Rare Kimura’s Disease in the Oral Cavity with Severe Sleep Apnea: Case Report and Literature Review

Kimura’s disease (KD) is a rare chronic inflammatory disorder that commonly occurs in Asian males. It mainly presents as painless subcutaneous masses or lymphadenopathy in the head and neck region. The incidence of KD in the oral cavity is quite rare. We reported a rare case of a 53-year-old male who had KD in his soft palate, hard palate and bilateral tonsils associated with severe sleep apnea. This patient underwent radiotherapy and exhibited a good response to the treatment. Throughout the 12-month follow-up period, the patient’s condition remained satisfactory. Of the other 14 reviewed cases of KD in the oral cavity, the lesions can occur in the buccal mucosa, hard and soft palate, and mouth floor with specific clinical features. We further summarized their manifestations and treatments in order to guide the future identification and management of KD with lesions in the oral cavity

Artificial cells from microfluidic electrospray for reactive oxygen species scavenging

Excess reactive oxygen species (ROS) are closely related to many diseases, and the removal of ROS is a crucial strategy for facilitating clinical treatment. Herein, inspired by the multicompartment and the ROS-eliminating pathway within cells, an artificial cell containing enzymatic inverse opal hydrogel particles (IOHPs) for ROS scavenging is presented. The IOHPs with different colors are integrated into the prepared artificial cells through a microfluidic electrospray platform. Benefiting from the structural color marks of the IOHPs and the fluid manipulability of the microfluidic electrospray technique, the composited artificial cells with tunable numbers and types of encapsulated enzymes were developed. The resultant artificial cells displayed excellent capability in scavenging ROS, and when they were used for the treatment of culture medium, they could protect the cells from ROS-related damage. These features indicate that such biomimetic microcapsules with artificial cell structures can be a powerful therapeutic tool for the treatment of ROS-related diseases

Effects of allelochemicals from tobacco root exudates on seed germination and seedling growth of tobacco

The composition of root exudates from two varieties (K 326 and NC 89) of tobacco were identified by GC-MS. Organic acids,amides and esters were the main constituents of the root exudates which differed in their qualitative and quantitative composition.Contents of cinnamic acid and nine other organic compounds was reduced in about 29% after 15 days of exposition to soil microflora.The effects of 6 organic acids (benzoic, cinnamic, lauric, myristic, palmitic and phthalic acids) identified intothe root exudates of tobacco varieties were evaluated on seed germination of tobacco.The cinnamic and benzoic acids were the most inhibitory on seed germination.Fil: Huiyong, Yu. Chinese Academy of Agricultural Sciences; ChinaFil: Hongbo, Liang. Chinese Academy of Agricultural Sciences; ChinaFil: Guoming, Shen. Chinese Academy of Agricultural Sciences; ChinaFil: Sampietro, Diego Alejandro. Chinese Academy of Agricultural Sciences; China. Universidad Nacional de Tucumán; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Xinxin, Gao. Chinese Academy of Agricultural Sciences; Chin