Acupuncture for erectile dysfunction: a randomized controlled trial. / é’ˆåˆºæ²»ç–—å‹ƒèµ·åŠŸèƒ½éšœç¢ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the clinical efficacy of acupuncture in treating erectile dysfunction (ED). METHODS: A total of 64 ED patients were randomly divided into an acupuncture group (32 cases, 2 case dropped out) and a western medication group (32 cases, 2 cases dropped out). In the acupuncture group, acupuncture treatment was applied at Baihui (GV 20), Qihai (CV 6), Guanyuan (CV 4), Zhongji (CV 3), Dahe (KI 12), Qugu (CV 2), Zusanli (ST 36), and etc., two groups of acupoints were used alternately, 30 min each time, once every other day. In the western medication group, 50 mg of sildenafil tablet was took orally 1 h before sexual activity. Both groups were treated for 30 d. The international index of erectile function citrate (IIEF-5) score, self rating anxiety scale (SAS) score, self rating depression scale (SDS) score, TCM syndrome score were observed before and after treatment, and in follow-up of 2 weeks after treatment completion, the serum testosterone (T) level was detected before and after treatment, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment and in follow-up, the IIEF-5 scores were increased compared with those before treatment in the two groups (P<0.01). In follow-up, the IIEF-5 score in the acupuncture group was ascended compared with that in the western medication group (P<0.05). Except for the SDS and TCM syndrome scores in the western medication group of follow-up, the SAS scores, SDS scores, and the TCM syndrome scores were decreased after treatment and in follow-up compared with those before treatment in the two groups (P<0.01, P<0.05); in the acupuncture group, the SAS scores, SDS scores and the TCM syndrome scores after treatment and in follow-up were lower than those in the western medication group (P<0.01). After treatment, the serum T levels were increased compared with those before treatment in the two groups (P<0.01). The total effective rate of the acupuncture group was 83.3% (25/30), and it was 86.7% (26/30) in the western medication group, there was no significant difference in total effective rate between the two groups (P>0.05). CONCLUSIONS: Acupuncture can effectively improve erectile function, anxiety and depression state, and TCM syndrome in ED patients, and has a advantage of posterior effect compared with western medication treatment.

Metabolomic Analysis Reveals Association between Decreased Ovarian Reserve and In Vitro Fertilization Outcomes.

In vitro fertilization (IVF) is a highly effective treatment for infertility; however, it poses challenges for women with decreased ovarian reserve (DOR). Despite the importance of understanding the impact of DOR on IVF outcomes, limited research has explored this relationship, particularly using omics approaches. Hence, we conducted a study to investigate the association between DOR and IVF outcomes, employing a metabolomic approach. We analyzed serum samples from 207 women undergoing IVF treatment, including 89 with DOR and 118 with normal ovarian reserve (NOR). Our findings revealed that DOR was significantly associated with unfavorable IVF outcomes, characterized by a reduced oocyte count, lower embryo quality, and decreased rates of pregnancy and live births. Furthermore, we identified 82 metabolites that displayed significant alterations in DOR patients, impacting diverse metabolic pathways. Notably, a distinct panel of metabolites, including palmitic acid, stearic acid, LysoPC(9:0(CHO)/0:0), PC(18:0/9:0(CHO)), and PC(16:0/9:0(CHO)), exhibited discriminatory power between the DOR and NOR groups, showcasing a strong correlation with IVF outcomes. These findings emphasize the crucial role of metabolomic disruptions in influencing IVF outcomes among women with DOR.

[Alignment method for metabolite chromatographic peaks using an N-acyl glycine retention index system].

Peak alignment is a crucial data-processing step in untargeted metabolomics analysis that aims to integrate metabolite data from multiple liquid chromatography-mass spectrometry (LC-MS) batches for enhanced comparability and reliability. However, slight variations in the chromatographic separation conditions can result in retention time (RT) shifts between consecutive analyses, adversely affecting peak alignment accuracy. In this study, we present a retention index (RI)-based chromatographic peak-shift correction (CPSC) strategy to address RT shifts and align chromatographic peaks for metabolomics studies. A series of N-acyl glycine homologues (C2-C23) was synthesized as calibrants, and an LC RI system was established. This system effectively corrected RT shifts arising from variations in flow rate, gradient elution, instrument systems, and chromatographic columns. Leveraging the RI system, we successfully adjusted the RT of raw data to mitigate RT shifts and then implemented the Joint Aligner algorithm for peak alignment. We assessed the accuracy of the RI-based CPSC strategy using pooled human fecal samples as a test model. Notably, the application of the RI-based CPSC strategy to a long-term dataset spanning 157 d as an illustration revealed a significant enhancement in peak alignment accuracy from 15.5% to 80.9%, indicating its ability to substantially improve peak-alignment precision in multibatch LC-MS analyses.

A dataset of branched fatty acid esters of hydroxy fatty acids diversity in foods.

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are a class of bioactive lipids that show therapeutic potential for diabetes, anti-cancer and inflammation. These FAHFAs can be obtained through dietary intake, potentially improving human health. However, there is currently inadequate knowledge regarding the presence and variety of FAHFAs in different foods. Herein, we profile FAHFAs from 12 typical food samples and 4 medicinal food samples with the aid of our previous established chemical isotope labeling-assisted liquid chromatography-mass spectrometry method and build a comprehensive dataset of FAHFA diversity. The dataset comprised a total of 1207 regioisomers belonging to 298 different families, with over 100 families being newly discovered for the first time. Therefore, our findings contribute valuable insights into the molecular diversity and presence of FAHFA in a range of foods. This dataset serves as a foundation for further exploration of the nutritional and medicinal functions of FAHFAs.

Annotation of cell types (ACT): a convenient web server for cell type annotation.

BACKGROUND: The advancement of single-cell sequencing has progressed our ability to solve biological questions. Cell type annotation is of vital importance to this process, allowing for the analysis and interpretation of enormous single-cell datasets. At present, however, manual cell annotation which is the predominant approach remains limited by both speed and the requirement of expert knowledge. METHODS: To address these challenges, we constructed a hierarchically organized marker map through manually curating over 26,000 cell marker entries from about 7000 publications. We then developed WISE, a weighted and integrated gene set enrichment method, to integrate the prevalence of canonical markers and ordered differentially expressed genes of specific cell types in the marker map. Benchmarking analysis suggested that our method outperformed state-of-the-art methods. RESULTS: By integrating the marker map and WISE, we developed a user-friendly and convenient web server, ACT ( http://xteam.xbio.top/ACT/ or http://biocc.hrbmu.edu.cn/ACT/ ), which only takes a simple list of upregulated genes as input and provides interactive hierarchy maps, together with well-designed charts and statistical information, to accelerate the assignment of cell identities and made the results comparable to expert manual annotation. Besides, a pan-tissue marker map was constructed to assist in cell assignments in less-studied tissues. Applying ACT to three case studies showed that all cell clusters were quickly and accurately annotated, and multi-level and more refined cell types were identified. CONCLUSIONS: We developed a knowledge-based resource and a corresponding method, together with an intuitive graphical web interface, for cell type annotation. We believe that ACT, emerging as a powerful tool for cell type annotation, would be widely used in single-cell research and considerably accelerate the process of cell type identification.

Determination of vitamin D metabolites in various biological samples through an improved chemical derivatization assisted liquid chromatography-tandem mass spectrometry approach.

Vitamin D (VD) metabolites are involved in a variety of important metabolic processes and physiological effects in organisms. Profiling of VD metabolites favors a deep understanding of the physiological role of VD. However, VD metabolites are difficult to detect due to their high chemical structural rigidity, structural similarity, and low sensitivities under liquid chromatography-tandem mass spectrometry (LC-MS). Herein, we present a chemical derivatization assisted LC-MS/MS strategy for the detection of VDs, in which 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) is employed to derivatize the conjugated diene of VD metabolites and provides sensitizing reporters for MS detection. After PTAD derivatization, the sensitivities of seven VD metabolites increased by 24-276 folds, with the limits of detection ranging from 3 to 20 pg mL-1. Using this method, we achieved a sensitive and accurate quantification of 7 VD metabolites (vitamin D2, vitamin D3, 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D2, 1,25-dihydroxyvitamin D3, and 1,24,25-trihydroxyvitamin D3) of the VD metabolic pathway in different trace biological samples, including human serum, mouse tissues (namely liver, kidney, lung, and spleen), and cells. We believe that the present method can provide a promising tool for an in-depth analysis of VD metabolism.

Co-Occurring EGFR S645C and EGFR L858R in a Patient with Lung Adenocarcinoma Induced Primary Resistance to Osimertinib.

Approximately 10-20% of patients demonstrate primary resistance to EGFR-TKIs, and different EGFR mutations vary in sensitivity to EGFR-TKIs. We report a case of a 78-year-old male with lung adenocarcinoma that EGFR L858R (AF = 1.32%) coexisting with EGFR S645C (AF = 7.13%) in his diagnosed tissues analyzed by NGS. The patient was primarily resistant to first-line osimertinib and rapidly progressed after pembrolizumab in combination with pemetrexed and bevacizumab, as demonstrated by persistently elevated CEA levels during treatment. ctDNA-based NGS analysis revealed loss of EGFR L858R while persistence of highly abundant EGFR S645C in the pleural fluid and plasma after treatment, suggesting that EGFR L858R may be a subclone. We provide the first clinical evidence of the primary resistance of EGFR S645C to osimertinib and emphasize the importance of identifying clones and subclones. Our patient did not respond to immunotherapy either, and preclinical studies have shown that EGFR S645C activates the MEK signaling pathway, the combination of EGFR-TKIs and MEK inhibitors may be effective.

Novel Peak Shift Correction Method Based on the Retention Index for Peak Alignment in Untargeted Metabolomics.

Peak alignment is a crucial step in liquid chromatography-mass spectrometry (LC-MS)-based large-scale untargeted metabolomics workflows, as it enables the integration of metabolite peaks across multiple samples, which is essential for accurate data interpretation. Slight differences or fluctuations in chromatographic separation conditions, however, can cause the chromatographic retention time (RT) shift between consecutive analyses, ultimately affecting the accuracy of peak alignment between samples. Here, we introduce a novel RT shift correction method based on the retention index (RI) and apply it to peak alignment. We synthesized a series of N-acyl glycine (C2-C23) homologues via the amidation reaction between glycine with normal saturated fatty acids (C2-C23) as calibrants able to respond proficiently in both mass spectrometric positive- and negative-ion modes. Using these calibrants, we established an N-acyl glycine RI system. This RI system is capable of covering a broad chromatographic space and addressing chromatographic RT shift caused by variations in flow rate, gradient elution, instrument systems, and LC separation columns. Moreover, based on the RI system, we developed a peak shift correction model to enhance peak alignment accuracy. Applying the model resulted in a significant improvement in the accuracy of peak alignment from 15.5 to 80.9% across long-term data spanning a period of 157 days. To facilitate practical application, we developed a Python-based program, which is freely available at https://github.com/WHU-Fenglab/RI-based-CPSC.

Computational Quantification of Cancer Immunoediting.

The remarkable success of cancer immunotherapy has revolutionized cancer treatment, emphasizing the importance of tumor-immune interactions in cancer evolution and treatment. Cancer immunoediting describes the dual effect of tumor-immune interactions: inhibiting tumor growth by destroying tumor cells and facilitating tumor escape by shaping tumor immunogenicity. To better understand tumor-immune interactions, it is critical to develop computational methods to measure the extent of cancer immunoediting. In this review, we provide a comprehensive overview of the computational methods for quantifying cancer immunoediting. We focus on describing the basic ideas, computational processes, advantages, limitations, and influential factors. We also summarize recent advances in quantifying cancer immunoediting studies and highlight future research directions. As the methods for quantifying cancer immunoediting are continuously improved, future research will further help define the role of immunity in tumorigenesis and hopefully provide a basis for the design of new personalized cancer immunotherapy strategies.

Partial Response to Crizotinib in a Lung Adenocarcinoma Patient with a Novel FBXO11 (Intergenic)-ALK (Exon 20-29) Fusion.

Intergenic-gene fusion detected by DNA-seq is particularly confusing for drug selection since the function of the intergenic region located upstream is unknown. We reported a case of a 49-year-old male with advanced lung adenocarcinoma, who was detected FBXO11 (intergenic)-ALK (exon 20-29) by DNA-seq, and FISH analysis revealed a positive result. The patient was treated with crizotinib and achieved a PR. The canonical EML4 (exon 1-13)-ALK (exon 20-29) fusion verified by RNA-seq suggested a complex EML4 (exon 1-13)-FBXO11 (intergenic)-ALK (exon 20-29) tripartite rearrangement at the DNA level. Our case emphasized the necessity of RNA-seq for verifying intergenic-gene fusion. Simultaneously, the pathogenic germline SLX4 variant and extensive CNVs of DNA segment were detected by DNA-seq deserves our attention.

Uncovering the Carboxylated Metabolome in Gut Microbiota-Host Co-metabolism: A Chemical Derivatization-Molecular Networking Approach.

Gut microbiota-host co-metabolites serve as essential mediators of communication between the host and gut microbiota. They provide nutrient sources for host cells and regulate gut microenvironment, which are associated with a variety of diseases. Analysis of gut microbiota-host co-metabolites is of great significance to explore the host-gut microbiota interaction. In this study, we integrated chemical derivatization, liquid chromatography-mass spectrometry, and molecular networking (MN) to establish a novel CD-MN strategy for the analysis of carboxylated metabolites in gut microbial-host co-metabolism. Using this strategy, 261 carboxylated metabolites from mouse feces were detected, which grouped to various classes including fatty acids, bile acids, N-acyl amino acids, benzoheterocyclic acids, aromatic acids, and other unknown small-scale molecular clusters in MN. Based on the interpretation of the bile acid cluster, a novel type of phenylacetylated conjugates of host bile acids was identified, which were mediated by gut microbiota and exhibited a strong binding ability to Farnesoid X receptor and Takeda G protein-coupled receptor 5. Our proposed strategy offers a promising platform for uncovering carboxylated metabolites in gut microbial-host co-metabolism.

[Bamboo-based medicinal moxibustion for chronic fatigue syndrome: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of bamboo-based medicinal moxibustion for chronic fatigue syndrome (CFS), and to preliminarily explore its action mechanism. METHODS: Sixty-four patients with CFS were randomly divided into a moxibustion group (32 cases, 1 case dropped off, 1 case excluded) and an acupuncture group (32 cases, 2 cases dropped off). The patients in the moxibustion group were treated with bamboo-based medicinal moxibustion, while the patients in the acupuncture group were treated with routine acupuncture. Both groups were treated once a day, 6 days as a course of treatment with 1 day interval, for a total of 2 courses of treatment. Before treatment, 1 and 2 courses into treatment and in the follow-up of 14 days after treatment, the fatigue scale-14 (FS-14) and somatic and psychological health report (SPHERE) scores were observed in the two groups. Before and after treatment, the contents of CD+3, CD+4, CD+8 of peripheral blood T lymphocyte subsets were measured and CD+4/CD+8 ratio was calculated; the clinical efficacy of the two groups was compared. RESULTS: Compared before treatment, the FS-14 and SPHERE scores in the two groups were decreased 1 and 2 courses into treatment and in the follow-up (P<0.01), and the FS-14 and SPHERE scores in the moxibustion group were lower than those in the acupuncture group (P<0.01, P<0.05). Compared before treatment, the contents of CD+3, CD+4 and CD+4/CD+8 ratio in the moxibustion group were increased after treatment (P<0.01). There was no significant difference of CD+3, CD+4, CD+8 and CD+4/CD+8 ratio between before and after treatment in the acupuncture group (P>0.05). After treatment, the contents of CD+3 and CD+4 in the moxibustion group were higher than those in the acupuncture group (P<0.05). The total effective rate was 93.3% (28/30) in the moxibustion group, which was higher than 73.3% (22/30) in the acupuncture group (P<0.05). CONCLUSION: Bamboo-based medicinal moxibustion could improve the physical and mental fatigue symptoms and psychological status in patients with CFS. Its effect may be related to regulating the contents of CD+3, CD+4 of peripheral blood T lymphocyte subsets and CD+4/CD+8 ratio.

Chemical isotope labeling assisted liquid chromatography-mass spectrometry method for simultaneous analysis of central carbon metabolism intermediates.

Central carbon metabolism pathway (CCM) is one of the most important metabolic pathways in all living organisms and play crucial function in aspect of organism life. However, the simultaneous detection of CCM intermediates remains challenging. Here, we developed a chemical isotope labeling combined with LC-MS method for simultaneous determination of CCM intermediates with high coverage and accuracy. By chemical derivatization with 2-(diazo-methyl)-N-methyl-N-phenyl-benzamide (2-DMBA) and d5-2-DMBA, all CCM intermediates obtain better separation and accurate quantification at a single LC-MS run. The obtained limits of detection of CCM intermediates ranged from 5 to 36 pg/mL. Using this method, we achieved simultaneous and accurate quantification of 22 CCM intermediates in different biological samples. Take account of the high detection sensitivity of the developed method, this method was further applied to the quantification of CCM intermediates at single-cell level. Finally, 21 CCM intermediates were detected in 1000 HEK-293T cells and 9 CCM intermediates were detected in mouse kidney glomeruli optical slice samples (10∼100 cells).

In-depth profiling of di(2-ethylhexyl) phthalate metabolic footprints in rats using click chemistry-mass spectrometry probes.

Di(2-ethylhexyl) phthalate (DEHP), the most widely used plasticizers in the world, has been regarded as an endocrine disrupting chemical with serious adverse health outcomes. Accumulating evidence strongly suggests that the undesirable biological effects of DEHP are meditated by its metabolites rather than itself. However, the metabolic footprints of DEHP in vivo are still unclear. Here we developed a click chemistry-assisted mass spectrometry (CC-MS) strategy for in-depth profiling DEHP metabolites in rats. An alkyne-modified DEHP analogue (alkyne-DEHP) was synthesized as a tracer for in vivo tracing, and a pair of MS probes (4-azido-nphenylbenzamide, 4-ANPA, and its deuterated reagent d5-4-ANPA) were prepared to specifically label the alkyne-DEHP metabolites, and prominently improve their detection sensitivity and selectivity. Using the CC-MS strategy, we successfully screened 247 alkyne-DEHP metabolites from rat urine, feces, and serum, including many unrevealed metabolites, such as oxidized phthalate diester metabolites and glucuronides of phthalate monoester metabolites. The discovery of new DEHP metabolites provides additional insights for understanding the metabolism of DEHP, which may be beneficial in exploring the mechanism underlying DEHP induced-toxicity in the future.

A strategy for screening and identification of new amino acid-conjugated bile acids with high coverage by liquid chromatography-mass spectrometry.

Bile acids (BAs) are a class of vital gut microbiota-host cometabolites, and they play an important role in maintaining gut microbiota-host metabolic homeostasis. Very recently, a new mechanism of BA anabolic metabolism mediated by gut microbiota (BA-amino acid conjugation) has been revealed, which provides a perspective for the research on BA metabolism and gut metabolome. In this study, we established a polarity-switching multiple reaction monitoring mass spectrometry-based screening method to mine amino acid-conjugated bile acids (AA-BAs) derived from host-gut microbiota co-metabolism. In addition, a retention time-based annotation strategy was further proposed to identify the AA-BA isomers and epimers. Using the developed methods, we successfully screened 118 AA-BA conjugates from mouse and human feces, 28 of them were confirmed by standards, and 62 putatively identified based on their predicted retention times. Moreover, we observed that the levels of most AA-BAs were significantly downregulated in the feces of chronic sleep deprivation mice, suggesting that the AA-BA metabolism was closely related to the physiological state of the host.

Validation of ESM1 Related to Ovarian Cancer and the Biological Function and Prognostic Significance.

Background: Ovarian cancer (OC), a serious gynecological malignant disease, remains an enormous challenge in early diagnosis and medical treatment. Based on the GEO and TCGA databases in R language, endothelial cell-specific molecule 1 (ESM1) was confirmed separately with the bioinformatic analysis tool. ESM1 has been demonstrated to be upregulated in multiple cancer types, but the oncogenic mechanism by which ESM1 promotes OC is still largely unknown. Methods: In this study, we used WGCNA and random survival forest variable screening to filter out ESM1 in OC differentially expressed genes (DEGs). Next, we confirmed the mRNA and protein levels of ESM1 in OC samples via PCR and IHC. The correlation between the ESM1 level and clinical data of OC patients was further confirmed, including FIGO stage, lymph node metastasis, and recurrence. The role of ESM1 in OC development was explored by several functional experiments in vivo and in vitro. Then, the molecular mechanisms of ESM1 were further elucidated by bioinformatic end experimental analysis. Results: ESM1 was significantly upregulated in OC and was positively correlated with PFS but negatively correlated with OS. ESM1 knockdown inhibited cell proliferation, apoptosis escape, the cell cycle, angiogenesis, migration and invasion in multiple experiments. Moreover, GSVA found that ESM1 was associated with the Akt pathway, and our results supported this prediction. Conclusion: ESM1 was closely correlated with OC development and progression, and it could be considered a novel biomarker and therapeutic target for OC patients.

Space Rather than Seasonal Changes Explained More of the Spatiotemporal Variation of Tropical Soil Microbial Communities.

Soil microbiomes play an essential role in maintaining soil geochemical cycle and function. Although there have been some reports on the diversity patterns and drivers of the tropical forest soil microbial community, how space and seasonal changes affect spatiotemporal distribution at the regional scales are poorly understood. Based on 260 soil samples, we investigated the spatiotemporal patterns of rubber plantations and rainforest soil microbial communities across the whole of Hainan Island, China during the dry and rainy seasons. We examined soil bacterial and fungal composition and diversity and the main drivers of these microbes using Illumina sequencing and assembly. Our results revealed that the diversity (both alpha and beta) spatiotemporal variation in microbial communities is highly dependent on regional location rather than seasonal changes. For example, the site explained 28.5% and 37.2% of the variation in alpha diversity for soil bacteria and fungi, respectively, and explained 34.6% of the bacterial variance and 14.3% of the fungal variance in beta diversity. Soil pH, mean annual temperature, and mean annual precipitation were the most important factors associated with the distribution of soil microbial communities. Furthermore, we identified that variations in edaphic (e.g., soil pH) and climatic factors (e.g., mean annual temperature [MAT] and mean annual precipitation [MAP]) were mainly caused by regional sites (P < 0.001). Collectively, our work provides empirical evidence that space, rather than seasonal changes, explained more of the spatiotemporal variation of soil microbial communities in tropical forests, mediated by regional location-induced changes in climatic factors and edaphic properties. IMPORTANCE The soil microbiomes communities of the two forests were not only affected by environmental factors (e.g., edaphic and climatic factors), but also by different dominant geographic factors. In particular, our work showed that spatial variation in bacterial and fungal community composition was mainly dominated by edaphic properties (e.g., pH) and climatic factors (e.g., MAT and MAP). Moreover, the environmental factors were mainly explained by geographic location effect rather than by seasonal effect, and environmental dissimilarity significantly increased with geographic distance. In conclusion, our study provides solid empirical evidence that space rather than season explained more of the spatiotemporal variation of soil microbial communities in the tropical forest.

Rapid and Economical Chemoselective Metabolomics Using Boronate Ester Formation on a Monolithic Substrate.

Although chemoselective labeling strategies show great potential in in-depth description of metabolomics, the associated time and expense limit applications in high-throughput and routine analysis. We report a fast and effective chemoselective labeling strategy based on multifunctionalized monolithic probes. A rapid pH-responsive boronate ester reaction was employed to immobilize and release probe molecules from substrate in 5 min. The mesoporous surface and hierarchically porous channels of the substrate allowed for accelerated labeling reactions. Moreover, the discernible boron beacons allowed for recognition of labeled metabolites with no need for expensive isotopic encoding. This new strategy has been successfully used for submetabolome analysis of yeast cells, serum, and faeces samples, with improved sensitivity for short chain fatty acids up to 1 600 times compared with non-labeled liquid chromatography-mass spectrometry (LC-MS) methods.

Identification of circulating immune landscape in ischemic stroke based on bioinformatics methods.

Ischemic stroke (IS) is a high-incidence disease that seriously threatens human life and health. Neuroinflammation and immune responses are key players in the pathophysiological processes of IS. However, the underlying immune mechanisms are not fully understood. In this study, we attempted to identify several immune biomarkers associated with IS. We first retrospectively collected validated human IS immune-related genes (IS-IRGs) as seed genes. Afterward, potential IS-IRGs were discovered by applying random walk with restart on the PPI network and the permutation test as a screening strategy. Doing so, the validated and potential sets of IS-IRGs were merged together as an IS-IRG catalog. Two microarray profiles were subsequently used to explore the expression patterns of the IS-IRG catalog, and only IS-IRGs that were differentially expressed between IS patients and controls in both profiles were retained for biomarker selection by the Random Forest rankings. CLEC4D and CD163 were finally identified as immune biomarkers of IS, and a classification model was constructed and verified based on the weights of two biomarkers obtained from the Neural Network algorithm. Furthermore, the CIBERSORT algorithm helped us determine the proportions of circulating immune cells. Correlation analyses between IS immune biomarkers and immune cell proportions demonstrated that CLEC4D was strongly correlated with the proportion of neutrophils (r = 0.72). These results may provide potential targets for further studies on immuno-neuroprotection therapies against reperfusion injury.

Profiling of Branched Fatty Acid Esters of Hydroxy Fatty Acids in Teas and Their Potential Sources in Fermented Tea.

Branched fatty acid ester of hydroxy fatty acid (FAHFA) is a class of natural lipid with important biological functions. In this study, we first profiled natural-origin FAHFAs in different teas using the chemical labeling-assisted liquid chromatography-mass spectrometry method. Consequently, we observed rich molecular diversity of FAHFAs with multiple regioisomers in teas. Additionally, the FAHFA contents had a positive relationship with the tea fermentation degree and a negative relationship with homologous fatty acids. Moreover, the highly accumulated FAHFAs (e.g., 3-MAHMA) in some postfermented teas (e.g., Fu brick tea) were also basically interpreted with regiospecificity of FAHFAs in both teas and fungus. This study revealed that tea is a rich natural source of FAHFAs, and some abundant FAHFAs might be the functional molecules accounting for the antidiabetic function of teas.