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Magnetic materials with noncolinear spin configurations have engendered significant interest in condensed matter physics due to their intriguing physical properties. In this study, we direct our attention towards the magnetic properties and critical behavior of single-crystal SmMn$_{2}$Ge$_{2}$, an itinerant magnet with numerous temperature-dependent magnetic phase transitions. Notably, SmMn$_{2}$Ge$_{2}$ displays significant magnetic anisotropy with easy magnetization direction switching from the $ c $ axis to the $ab$ plane as temperature decreases. The critical behavior of the ferromagnetic transition occurring above room temperature is thoroughly examined. Reliable and self-consistent critical exponents, including $ \beta = 0.292(2) $, $ \gamma=0.924(8) $, and $ \delta = 4.164(6)$, along with the Curie temperature, $T_{\rm c}=347$ K, are extracted through various methods, which provide evidence for the coexistence of multiple magnetic interactions in SmMn$_{2}$Ge$_{2}$. Further analysis reveals that the magnetic interaction of SmMn$_{2}$Ge$_{2}$ is a long-range type with the interaction distance decaying as $ J(r)\sim r^{-4.35} $.

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), Y RNA, and lncRNA, as well as protein-coding mRNA fragments. Computational deconvolution of exRBP RNA cargo reveals associations of exRBPs with extracellular vesicles, lipoproteins, and ribonucleoproteins across human biofluids. Overall, we mapped the distribution of exRBPs across human biofluids, presenting a resource for the community.

Background The prognosis of peripheral T cell lymphomas (PTCLs) varies greatly. This study aimed at generating a prognostic nomogram based on differentially expressed genes (DEGs).Methods Firstly, we collected RNA transcripts from Gene Expression Omnibus and identified DEGs. Secondly we used univariate Cox regression, Least absolute shrinkage and selection operator (LASSO) to screen the independent risk factors to construct nomogram in the training cohort. Thirdly, we evaluate its prediction accuracy via decision curves analysis (DCA), receiver operating characteristic (ROC) and calibration rate to confirm its performance on survival in training and validation cohort. Then we carried out subgroup analysis in training and validation to eliminate the effects of age, gender, and pathological subtype. Lastly, to verify feasibility of nomogram in practice, we applied immunohistochemistry to clinical samples and analyzed the relationship between IHC scores and prognosis.Results The 702 DEGs between 40 PTCLs and 20 non-tumor patients were identified. Then ANGPTL2, CPSF4, CLIC4 and OTUD6B were screened out as independent risk factors via univariate Cox regression and LASSO. The DCA, ROC, Harrell’s concordance index (c-index) and calibration rate showed nomogram predicting more accurately than any single specific transcript. The results showed PTCLs with higher nomogram-score had a longer survival, regardless of age, gender and pathological subtype. Finally, the high expression level of ANGPTL2, CPSF4 and OTUD6B related to poor prognosis. Higher expression of CLIC4 related to longer survival.Conclusion This nomogram showed the favorable clinical applicability, regardless of age, gender and pathological subtype.

There is growing evidence that extracellular vesicles (EVs) play a functional role in tissue repair and anti-aging by transferring the contents of donor cells to recipient cells. We hypothesized that Dauer (C. elegans), known as “ageless” nematodes, can also secrete extracellular vesicles and influence the lifespan of C. elegans. Here, we isolated EVs of dauer larvae (dauer EVs). Dauer EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA), and Western blot analysis. Wild-type C. elegans were fed in the presence or absence of dauer EVs and tested for a range of phenotypes, including longevity, mobility and reproductive capacity. Results showed that dauer EVs increased the average lifespan of nematodes by 15.74%, improved mobility, slowed age-related pigmentation as well as body length, and reduced the accumulation of reactive oxygen species and lipids, while not impairing nematode reproductive capacity. These findings suggest that dauer EVs can extend the lifespan of C. elegans as well as the healthy lifespan by reducing ROS accumulation, with potential anti-aging capacity.

High levels of reactive oxygen species (ROS) result in oxidative stress, which damages cells and leads to the development of many diseases. Macroautophagy/autophagy plays an important role in protecting cells from diverse stress stimuli including oxidative stress. However, the molecular mechanisms of autophagy activation in response to oxidative stress remain largely unclear. In this study, we showed that TRAF6 mediates oxidative stress-induced ATG9A ubiquitination at two C-terminal lysine residues (K581 and K838). ATG9A ubiquitination promotes its association with BECN1, BECN1-PIK3C3/VPS34-UVRAG complex assembly and PIK3C3/VPS34 activation, thereby activating autophagy and endocytic trafficking. We also identified TNFAIP3/A20 as a negative regulator of oxidative-induced autophagy by counteracting TRAF6-mediated ATG9A ubiquitination. Moreover, ATG9A depletion attenuates LPS-induced autophagy and causes aberrant TLR4 signaling and inflammatory responses. Our findings revealed a critical role of ATG9A ubiquitination in oxidative stress-induced autophagy, endocytic trafficking and innate immunity.

Animal studies suggest that the apolipoprotein E ε4 ( APOE ε4) allele is a culprit of early microglial activation in Alzheimer’s disease (AD). Here, we tested the association between APOE ε4 status and microglial activation in living individuals across the aging and AD spectrum. We studied 118 individuals with positron emission tomography for amyloid-β (Aβ; [ 18 F]AZD4694), tau ([ 18 F]MK6240), and microglial activation ([ 11 C]PBR28). We found that APOE ε4 carriers presented increased microglial activation relative to noncarriers in early Braak stage regions within the medial temporal cortex accounting for Aβ and tau deposition. Furthermore, microglial activation mediated the Aβ-independent effects of APOE ε4 on tau accumulation, which was further associated with neurodegeneration and clinical impairment. The physiological distribution of APOE mRNA expression predicted the patterns of APOE ε4-related microglial activation in our population, suggesting that APOE gene expression may regulate the local vulnerability to neuroinflammation. Our results support that the APOE ε4 genotype exerts Aβ-independent effects on AD pathogenesis by activating microglia in brain regions associated with early tau deposition.

Fetal alcohol spectrum disorder (FASD) caused by mother's exposure to alcohol during pregnancy is a congenital neurological disease of the fetus resulting in fetal developmental and intellectual disabilities, cognitive impairment, and coordination disorder. Excess oxidative stress and neuroinflammatory responses were an important factor in neuropathological changes in FASD. Astaxanthin (AST) was a potent antioxidant and anti-inflammatory carotenoid. Therefore, this study proposed to explore how AST treatment can ameliorate morphological changes in the hippocampus and cognitive impairment in FASD rats by reducing oxidative stress and neuroinflammation in the brain. An alcohol atomizer was used from postnatal day (P) 2 to P10 to induce the FASD rat model. They were treated with AST (10 mg/kg body weight/day, intraperitoneal injection) for 8 consecutive days starting at P53 and sacrificed at P60. FASD rats had growth retardation and facial dysmorphologies, excessive oxidative stress and neuroinflammation in the hippocampus, decreased choline acetyltransferase (ChAT) expression in MS nucleus, spine loss on hippocampal CA1 pyramidal neurons, and poor performance in spatial learning and memory and sensory-motor coordination. After AST treatment, oxidative stress, neuroinflammation, cholinergic system, excitatory synaptic structure and behavior of FASD rats improved. Therefore, our study provided evidence to support the proposal that AST could be considered to treat FASD.

Gold-standard diagnosis of Alzheimer’s disease (AD) relies on histopathological staging systems. Using the topographical information from [18F]MK6240 tau positron-emission tomography (PET), we applied the Braak tau staging system to 324 living individuals. We used PET-based Braak stage to model the trajectories of amyloid-β, phosphorylated tau (pTau) in cerebrospinal fluid (pTau181, pTau217, pTau231 and pTau235) and plasma (pTau181 and pTau231), neurodegeneration and cognitive symptoms. We identified nonlinear AD biomarker trajectories corresponding to the spatial extent of tau-PET, with modest biomarker changes detectable by Braak stage II and significant changes occurring at stages III–IV, followed by plateaus. Early Braak stages were associated with isolated memory impairment, whereas Braak stages V–VI were incompatible with normal cognition. In 159 individuals with follow-up tau-PET, progression beyond stage III took place uniquely in the presence of amyloid-β positivity. Our findings support PET-based Braak staging as a framework to model the natural history of AD and monitor AD severity in living humans.

Abnormal mitochondrial metabolism has been described in the Alzheimer's disease (AD) brain. However, the relationship between AD pathophysiology and key mitochondrial processes remains elusive. The purpose of this study was to investigate whether mitochondrial complex I dysfunction is associated with amyloid aggregation or glucose metabolism and brain atrophy in patients with mild AD using positron emission tomography (PET).Amyloid- and tau-positive symptomatic AD patients with clinical dementia rating 0.5 or 1 (N = 30; mean age ± standard deviation: 71.8 ± 7.6 years) underwent magnetic resonance imaging and PET scans with [[In symptomatic cases, although mitochondrial complex I reduction is linked to a wide range of downstream neurodegenerative processes such as hypometabolism, atrophy, and cognitive decline, a link to amyloid was not observable. The data presented here support [

The mechanisms by which the apolipoprotein E ε4 (APOEε4) allele influences Alzheimer’s disease (AD) pathophysiological progression are poorly understood. Here, we tested the association of APOEε4 carriership and amyloid-β (Aβ) burden with longitudinal tau pathology progression. We studied 104 individuals across the aging and AD spectrum who underwent clinical assessments, APOE genotyping, magnetic resonance imaging, positron emission tomography (PET) for Aβ ([18F]AZD4694) and tau ([18F]MK-6240) at baseline, as well as a follow-up tau-PET scan (mean follow-up, 2.4 years). We further assessed longitudinal changes in tau phosphorylation (plasma phosphorylated tau at threonine 217 [p-tau217+]), brain atrophy (gray matter density), and clinical function (clinical dementia rating scale sum of boxes). We found that APOEε4 carriership potentiates Aβ effects on longitudinal tau tangle accumulation over two years. The APOEε4-potentiated Aβ effects on tangles were mediated by longitudinal plasma p-tau217+ increase. This longitudinal tau accumulation as measured by PET was accompanied by brain atrophy and clinical decline. Our results support a model in which the APOEε4 allele plays a key role in Aβ downstream effects on the aggregation of phosphorylated tau in the form of neurofibrillary tangles in the living human brain.

A classical early sign of typical Alzheimer’s disease is memory decline, which has been linked to the aggregation of tau in the medial temporal lobe. Verbal delayed free recall and recognition tests have consistently probed useful to detect early memory decline, and there is substantial debate on how performance, particularly in recognition tests, is differentially affected through health and disease in older adults. Using in vivo PET-Braak staging, we investigated delayed recall and recognition memory dysfunction across the Alzheimer’s disease spectrum. Our cross-sectional study included 144 cognitively unimpaired elderly, 39 amyloid-β+ individuals with mild cognitive impairment and 29 amyloid-β+ Alzheimer’s disease patients from the Translational Biomarkers in Aging and Dementia cohort, who underwent [18F]MK6240 tau and [18F]AZD4694 amyloid PET imaging, structural MRI and memory assessments. We applied non-parametric comparisons, correlation analyses, regression models and voxel-wise analyses. In comparison with PET-Braak Stage 0, we found that reduced, but not clinically significant, delayed recall starts at PET-Braak Stage II (adjusted P < 0.0015), and that recognition (adjusted P = 0.011) displayed a significant decline starting at PET-Braak Stage IV. While performance in both delayed recall and recognition related to tau in nearly the same cortical areas, further analyses showed that delayed recall rendered stronger associations in areas of early tau accumulation, whereas recognition displayed stronger correlations in mostly posterior neocortical regions. Our results support the notion that delayed recall and recognition deficits are predominantly associated with tau load in allocortical and neocortical areas, respectively. Overall, delayed recall seems to be more dependent on the integrity of anterior medial temporal lobe structures, while recognition appears to be more affected by tau accumulation in cortices beyond medial temporal regions.

PurposeThis study aims to examine members’ perceptions of interactivity in brand communities on social networking sites in the Super Basketball League (SBL) context in Taiwan.Design/methodology/approachThe proposed model was empirically evaluated using survey data collected from 332 followers of the SBL teams’ Facebook pages on their perceptions of brand communities. Structural equation modeling was used to examine the relationships in the research model.FindingsThe results suggest significant relationships between perceived interactivity and community benefits, including special treatment, social influence, sense of membership and the notion that community satisfaction has a strong and positive effect on brand loyalty. Both social influence and a sense of membership positively affect community satisfaction. However, special treatment negatively affects community satisfaction. Perceived interactivity positively affects a sense of membership and social influence, which, in turn, positively affect community satisfaction.Originality/valueThis study examines the effects of members’ perceived interactivity and community benefits. The results significantly advance the understanding of the antecedents of members’ loyalty to specific brands. The study offers insights into practical ways of improving community satisfaction and brand loyalty by running brand communities on social networking sites. The findings also augment the theory of brand management.

A new kind of bio-based polyamide 5,6 (PA56) fiber has been synthesized from adipic acid and 1,5-pentanediamine. In this report, the characterization, antistatic treatment, mechanical properties, m...

Background: The growing cardiovascular disease (CVD) epidemic calls for further research to identify novel biomarkers for earlier detection and as potential therapeutic targets. Biomarkers Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMP-2, and MMP-9) are linked to proatherogenic and proinflammatory pathways of CVD development, the majority of which are coronary artery disease (CAD) and stroke. We evaluated potential factors affecting these four biomarkers and established their association with CVD. Methods: This is a cross-sectional analysis using a nested case-control design involving 580 participants aged 21–75 years from the prospective multi-ethnic cohort study. A total of 290 CVD cases and 290 age-and sex-matched controls were identified. All participants underwent interviews, health screenings, and provided blood samples, including biomarkers RANTES, EMMPRIN, and MMPs. CVD was defined based on previous medical history. Results: The average age of the participants was 55.7(SD = 10.3) years of age, and 34.6% were female. Arrhythmia history and low-density lipoprotein (LDL) levels were significant factors of logEMMPRIN (β = −0.124 [−0.245, −0.003] and β = 0.111 [0.0, 0.191], respectively). Only female sex (β = 0.189 [0.078, 0.300]) for logRANTES and age (β = 0.033 [0.010, 0.055]) for logMMP-2 and logMMP-9 were significant. The Indian ethnicity (β = 0.192 [0.048, 0.335]) and highly sensitive C-reactive protein (hs-CRP) levels (β = 0.063 [0.011, 0.116]) were statistically significant for logMMP-9. No association was detected between biomarkers and CVD. Conclusions: In this multi-ethnic study cohort, RANTES was associated with sex, EMMPRIN was associated with a history of arrhythmia and LDL levels, MMP-2 with age, and MMP-9 with ethnicity and hs-CRP levels. The biomarker serum levels were not associated with CVD.

PoDPBT, an O-benzoyltransferase belonging to the BAHD family, can catalyze the benzoylation of 8-debenzoylpaeoniflorin to paeoniflorin. PoDPBT is the first enzyme demonstrated to be involved in the modification stage of paeoniflorin biosynthesis. DFGGG, a new DFGWG-like motif, was revealed in the BAHD family. The transcriptome database provides a resource for further investigation of other enzyme genes involved in paeoniflorin biosynthesis.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other. To investigate this, we used unbiased quantitative mass spectrometry-based proteomics to examine the most proximal fluid to the brain, cerebrospinal fluid (CSF). This was to ascertain if the proteome profile of one was the same or different from the other. We examined two separate groups of ME/CFS, one with (n=15) and one without (n=15) fibromyalgia. We quantified a total of 2,083 proteins using immunoaffinity depletion, tandem mass tag isobaric labeling and offline two-dimensional liquid chromatography coupled to tandem mass spectrometry, including 1,789 that were quantified in all the CSF samples. ANOVA analysis did not yield any proteins with an adjusted p-value < 0.05. This supports the notion that ME/CFS and fibromyalgia as currently defined are not distinct entities.

The burden imposed by the COVID-19 pandemic deferentially interferes with the outcomes of clinical trials of aging and dementia. We examined the impact of the lockdown on cognitive impairment due to Alzheimer’s Disease (AD), anxiety, and COVID-19-related stress in participants from the Translational Biomarkers In Aging and Dementia (TRIAD) cohort using neuropsychiatric assessments, tau and amyloid PET. We found that, before the lockdown, anxiety was higher in cognitively impaired individuals (CI) and positively associated with brain tau load. However, during the lockdown, anxiety increased only in the cognitively unimpaired (CU) and was positively associated with COVID-19 related stress. Interestingly, we found that in patients, tau load was anti-correlated with higher anxiety during lockdown. Our findings contribute to a framework for interpreting the effects of the pandemic on neuropsychiatric symptoms among clinical trial participants. Collectively, our results suggest that caregivers are more vulnerable to external stressors than patients.

Microglial activation is an early phenomenon in Alzheimer’s disease (AD) that may occur prior to and independently of amyloid-β (Aβ) aggregation. Recent studies in transgenic animal models suggest that the apolipoprotein E ε4 (APOEε4) allele may be a culprit of early microglial activation in AD. However, it is unclear whether the APOEε4 genotype is associated with microglial reactivity in the living human brain. Here, we tested whether APOEε4 carriership is associated with microglial activation in individuals across the aging and AD spectrum. We studied 118 individuals who had positron emission tomography (PET) for Aβ ([18F]AZD4694), tau ([18F]MK6240), and microglial activation ([11C]PBR28), as well as clinical, genetic, and magnetic resonance imaging data. We found that APOEε4 carriership was associated with increased microglial activation mainly in early Braak-staging regions within the medial temporal cortex, and this effect of APOEε4 was independent of Aβ and tau deposition. Furthermore, microglial activation mediated the Aβ-independent effects of APOEε4 on downstream tau accumulation, neurodegeneration, and clinical impairment. Interestingly, the physiological distribution of APOE mRNA expression, obtained from the Allen Human Atlas, predicted the patterns of APOEε4-related microglial activation in our population, suggesting that the deleterious effects of APOEε4 occur at the level of gene expression. These results support a model in which the APOEε4 has Aβ-independent effects on AD pathogenesis by activating microglia in brain regions associated with early tau deposition. Our findings provide a rationale for the development of novel AD therapies targeting the interplay between ApoE and neuroinflammation.

Two new cycloartane triterpenoids, (24 R)-cycloartane-3β,24,25,30-tetrol (1) and (24 R)-24,25,30-trihydroxy-9,19-cycloartane-3-one (2), along with three known compounds (3-5) were isolated from leaves and twigs of Aphanamixis polystachya. The new compounds were elucidated based on comprehensive spectroscopic analysis, including 1 D, 2 D NMR and HREIMS. The in vitro cytotoxic activities evaluation of five human cancer cell lines revealed that compound 1 exhibited cytotoxic activity on all of tested human cancer cell lines, while compound 2 only had specific activity on SMMC-7721 cell line.

The technology of wind power is being widely developed worldwide. Ensuring the reliable operation of wind turbine systems is of significance. A popular tool to identify the potential risk of an eng...

Nanotechnology gives rise to new breakthroughs and developments in various fields. The applications of advanced nanotechnology may resolve the current technical problems encountered in stem cell research. Nanotechnology has gained significant attention in both academic research and the biomedical industry in recent years. In this mini-review article, the progress of nanotechnology-aided stem cell studies has been surveyed, and the in vitro and in vivo applications of nanotechnology have been introduced. The in vitro studies are divided into three categories: isolation, detection, and regulation. The progress of in vivo studies and trends in biomedical applications have also been addressed.

Chaperone-mediated autophagy (CMA) is a protein degradation mechanism through lysosomes. By targeting the KFERQ motif of the substrate, CMA is responsible for the degradation of about 30% of cytosolic proteins, including a series of proteins associated with neurodegenerative diseases (NDs). The fact that decreased activity of CMA is observed in NDs, and ND-associated mutant proteins, including alpha-synuclein and Tau, directly impair CMA activity reveals a possible vicious cycle of CMA impairment and pathogenic protein accumulation in ND development. Given the intrinsic connection between CMA dysfunction and ND, enhancement of CMA has been regarded as a strategy to counteract ND. Indeed, genetic and pharmacological approaches to modulate CMA have been shown to promote the degradation of ND-associated proteins and alleviate ND phenotypes in multiple ND models. This review summarizes the current knowledge on the mechanism of CMA with a focus on its relationship with NDs and discusses the therapeutic potential of CMA modulation for ND.

Introduction[18F]MK6240 is a tau-PET tracer that quantifies brain tau neurofibrillary tangles (NFT) load in Alzheimer’s disease (AD). The aims of our study are to test the stability of common reference regions estimates in the cerebellum over time and across diagnoses and evaluate the effects of age-related and off-target retention in the longitudinal quantification of [18F]MK6240 in target regions.MethodsWe assessed reference, target, age-related and off-target regions in 125 individuals across the aging and AD spectrum with longitudinal [18F]MK6240 standardized uptake values (SUV) and ratios (SUVR) (2.25± 0.4 years of follow-up duration). We obtained SUVR values from meninges, a region exhibiting frequent off-target retention of [18F]MK6240, as well as compared tracer uptake between cognitively unimpaired young (CUY, mean age: 23.41± 3.3 years) and cognitively unimpaired older adults (CU, amyloid-β and tau negative, mean age: 58.50± 9.0 years) to identify possible, non-visually apparent, age-related signal. Two-tailed t-test and Pearson correlations tested the difference between groups and associations between changes in region uptake, respectively.ResultsInferior cerebellar grey (CG) and full CG presented stable SUV cross-sectionally and over time, across diagnosis and Aβ status. [18F]MK6240 uptake was significantly different between CU young and adults mostly in putamen/pallidum (affecting ∼75% of the region) but also in Braak II region (affecting ∼35%), comprised of the entorhinal cortex and hippocampus. Changes in meningeal and putamen/pallidum SUVRs were not significantly different from zero, nor varied across diagnostic groups. We did not observe significant correlations between longitudinal changes in age-related or meningeal off-target retention and changes in target regions, whereas changes in all target regions were highly correlated.ConclusionInferior and full CG were similar across diagnostic groups cross-sectionally and stable over time, and thus were deemed suitable reference regions for quantification. Despite this not being visually perceptible, [18F]MK6240 has age-related retention in subcortical regions, in much lower magnitude but topographically co-localized with the most significant off-target signal of the first-generation tau tracers. The lack of correlation between changes in age-related/meningeal and target retention suggests little influence of possible off-target signals on longitudinal tracer quantification. On the other hand, the age-related tracer retention in Braak II needs to be further investigated. Future post-mortem studies should elucidate the source of the newly reported age-related [18F]MK6240 signal, and in vivo studies should further explore its impact on tracer quantification.

HIV/AIDS pandemic remains the world's most severe public health challenge, especially for HIV/AIDS immunological nonresponders (HIV/AIDS-INRs), who tend to have higher mortality. Due to the advantages in promoting patients' immune reconstitution, Traditional Chinese medicine (TCM) has become one of the mainstays of complementary treatments for HIV/AIDS-INRs. Given that effective TCM treatments largely depend on precise syndrome differentiation, there is an increasing interest in exploring biological evidence for the classification of TCM syndromes in HIV/AIDS-INRs. In our study, to identify the typical HIV/AIDS-INRs syndrome, an epidemiological survey was first conducted in the Liangshan prefecture (China), a high HIV/AIDS prevalence region. The key TCM syndrome, Yang deficiency of spleen and kidney (YDSK), was evaluated by using a tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS). A total of 62 differentially expressed proteins (DEPs) of YDSK syndrome compared with healthy people were screened out. Comparative bioinformatics analyses showed that DEPs in YDSK syndrome were mainly associated with response to wounding and acute inflammatory response in the biological process. The pathway annotation is mainly enriched in complement and coagulation cascades. Finally, the YDSK syndrome-specific DEPs such as HP and S100A9 were verified by ELISA, and confirmed as potential biomarkers for YDSK syndrome. Our study may lay the biological and scientific basis for the specificity of TCM syndromes in HIV/AIDs-INRs, and may provide more opportunities for the deep understanding of TCM syndromes and the developing more effective and stable TCM treatment for HIV/AIDS-INRs.中文摘要艾滋病仍然是全世界最严重的公共卫生挑战, 尤其是对艾滋病免疫无应答者而言, 他们往往有更高的死亡率。由于中医药在促进患者免疫重建方面优势突出, 现已成为艾滋病免疫无应答者补充治疗的支柱之一。鉴于有效的中医药治疗基于精准的辨证, 探索艾滋病免疫重建不全中医证候分类的生物学依据备受青睐。在我们的研究中, 为了确定艾滋病免疫无应答者的中医证候分布规律, 首先在我国艾滋病高发区凉山州进行了流行病学调查。接着我们采用TMT-LC-MS/MS技术对典型中医证候脾肾阳虚证进行了蛋白组学研究, 筛选出62种差异表达蛋白。通过生物信息分析显示, 脾肾阳虚证中的差异表达蛋白主要与生物过程中的创伤反应和急性炎症反应等有关。通路富集主要集中在补体和凝血级联等方面。最后, 利用ELISA检测方法对脾肾阳虚证候特异性蛋白HP和S100A9进行验证, 最终将这两种证候特异性蛋白确认为脾肾阳虚证的生物标记物。这为艾滋病免疫无应答中医证候的特异性奠定了生物学和科学基础, 为深入了解中医证候, 开发更有效、更稳定的中医治疗提供了更多机会。.

Our previous findings have shown that the chlorophyllides composites have anticancer activities to breast cancer cell lines (MCF-7 and MDA-MB-231). In the present study, microarray gene expression profiling was utilized to investigate the chlorophyllides anticancer mechanism on the breast cancer cells lines. Results showed that chlorophyllides composites induced upregulation of 43 and 56 differentially expressed genes (DEG) in MCF-7 and MDA-MB-231 cells, respectively. In both cell lines, chlorophyllides composites modulated the expression of annexin A4 (ANXA4), chemokine C-C motif receptor 1 (CCR1), stromal interaction molecule 2 (STIM2), ethanolamine kinase 1 (ETNK1) and member of RAS oncogene family (RAP2B). Further, the KEGG annotation revealed that chlorophyllides composites modulated DEGs that are associated with the endocrine system in MCF-7 cells and with the nervous system in MDA-MB-231 cells, respectively. The expression levels of 9 genes were validated by quantitative reverse transcription PCR (RT-qPCR). The expression of CCR1, STIM2, ETNK1, MAGl1 and TOP2A were upregulated in both chlorophyllides composites treated-MCF-7 and MDA-MB-231 cells. The different expression of NLRC5, SLC7A7 and PKN1 provided valuable information for future investigation and development of novel cancer therapy.

Effective phosphoproteome of nanoscale sample analysis remains a daunting task, primarily due to significant sample loss associated with non-specific surface adsorption during enrichment of low stoichiometric phosphopeptide. We developed a novel tandem tip phosphoproteomics sample preparation method that is capable of sample cleanup and enrichment without additional sample transfer, and its integration with our recently developed SOP (Surfactant-assisted One-Pot sample preparation) and iBASIL (improved Boosting to Amplify Signal with Isobaric Labeling) approaches provides a streamlined workflow enabling sensitive, high-throughput nanoscale phosphoproteome measurements. This approach significantly reduces both sample loss and processing time, allowing the identification of >3,000 (>9,500) phosphopeptides from 1 (10) µg of cell lysate using the label-free method without a spectral library. It also enabled precise quantification of ∼600 phosphopeptides from 100 cells sorted by FACS (single-cell level input for the enriched phosphopeptides) and ∼700 phosphopeptides from human spleen tissue voxels with a spatial resolution of 200 µm (equivalent to ∼100 cells) in a high-throughput manner. The new workflow opens avenues for phosphoproteome profiling of mass-limited samples at the low nanogram level.

A broad variety of unactivated acyclic and alicyclic substrates cleanly undergo site-selective alkenylation of unactivated C(sp3 )-H bonds with 1,2-bis(phenylsulfonyl)ethene in the presence of persulfate. This simple transformation furnishes (E)-2-alkylvinylphenylsulfones in up to 88 % yield. In contrast with the previously reported decatungstate protocol, the current method is applicable to alkenylation of sterically hindered C-H bonds. This important advantage significantly broadens the substrate scope, and is attributed to the compact size of the sulfate radical employed in the C-H activation and cleavage.

In the era of big data, the research on clustering technologies is a popular topic because they can discover the structure of complex data sets with minimal prior knowledge. Among the existing soft clustering technologies, as an extension of fuzzy c-means (FCM) algorithm, the intuitionistic FCM (IFCM) algorithm has been widely used due to its superiority in reducing the effects of outliers/noise and improving the clustering accuracy. In the existing IFCM algorithm, the measurement of proximity degree between a pair of objects and the determination of parameters are two critical problems, which have considerable effects on the clustering results. Therefore, we propose an improved IFCM clustering technique in this paper. Firstly, a novel weighted proximity measure, which aggregates weighted similarity and correlation measures, is proposed to evaluate not only the closeness degree but also the linear relationship between two objects. Subsequently, genetic algorithms are utilized for identifying the optimal parameters. Lastly, experiments on the proposed IFCM technique are conducted on synthetic and UCI data sets. Comparisons with other approaches in cluster evaluation indexes indicate the effectiveness and superiority of our method.

Background: Approximately 85% of the U.S. military active duty population is male and less than 50 years of age, with elevated levels of known risk factors for oropharyngeal squamous cell carcinoma (OPSCC), including smoking, excessive use of alcohol, and greater numbers of sexual partners, and elevated prevalence of human papilloma virus (HPV). Given the recent rise in incidence of OPSCC related to the HPV, the Department of Defense Serum Repository provides an unparalleled resource for longitudinal studies of OPSCC in the military for the identification of early detection biomarkers. Methods: We identified 175 patients diagnosed with OPSCC with 175 matched healthy controls and retrieved a total of 978 serum samples drawn at the time of diagnosis, 2 and 4 years prior to diagnosis, and 2 years after diagnosis. Following immunoaffinity depletion, serum samples were analyzed by targeted proteomics assays for multiplexed quantification of a panel of 146 candidate protein biomarkers from the curated literature. Results: Using a Random Forest machine learning approach, we derived a 13-protein signature that distinguishes cases versus controls based on longitudinal changes in serum protein concentration. The abundances of each of the 13 proteins remain constant over time in control subjects. The AUC for the derived Random Forest classifier was 0.90. Conclusions: This 13-protein classifier is highly promising for detection of OPSCC prior to overt symptoms. Impact: Use of longitudinal samples has significant potential to identify biomarkers for detection and risk stratification.