Mechanical and chemical itch regulated by neuropeptide Y-Y1 signaling.

Itch is a somatosensory sensation to remove potential harmful stimulation with a scratching desire, which could be divided into mechanical and chemical itch according to diverse stimuli, such as wool fiber and insect biting. It has been reported that neuropeptide Y (NPY) neurons, a population of spinal inhibitory interneurons, could gate the transmission of mechanical itch, with no effect on chemical itch. In our study, we verified that chemogenetic activation of NPY neurons could inhibit the mechanical itch as well as the chemical itch, which also attenuated the alloknesis phenomenon in the chronic dry skin model. Afterwards, intrathecal administration of NPY1R agonist, [Leu31, Pro34]-NPY (LP-NPY), showed the similar inhibition effect on mechanical itch, chemical itch and alloknesis as chemo-activation of NPY neurons. Whereas, intrathecal administration of NPY1R antagonist BIBO 3304 enhanced mechanical itch and reversed the alloknesis phenomenon inhibited by LP-NPY treatment. Moreover, selectively knocking down NPY1R by intrathecal injection of Npy1r siRNA enhanced mechanical and chemical itch behavior as well. These results indicate that NPY neurons in spinal cord regulate mechanical and chemical itch, and alloknesis in dry skin model through NPY1 receptors.

Oroxin A alleviates early brain injury after subarachnoid hemorrhage by regulating ferroptosis and neuroinflammation.

BACKGROUND: Subarachnoid hemorrhage (SAH), a severe subtype of stroke, is characterized by notably high mortality and morbidity, largely due to the lack of effective therapeutic options. Although the neuroprotective potential of PPARg and Nrf2 has been recognized, investigative efforts into oroxin A (OA), remain limited in preclinical studies. METHODS: SAH was modeled in vivo through filament perforation in male C57BL/6 mice and in vitro by exposing HT22 cells to hemin to induce neuronal damage. Following the administration of OA, a series of methods were employed to assess neurological behaviors, brain water content, neuronal damage, cell ferroptosis, and the extent of neuroinflammation. RESULTS: The findings indicated that OA treatment markedly improved survival rates, enhanced neurological functions, mitigated neuronal death and brain edema, and attenuated the inflammatory response. These effects of OA were linked to the suppression of microglial activation. Moreover, OA administration was found to diminish ferroptosis in neuronal cells, a critical factor in early brain injury (EBI) following SAH. Further mechanistic investigations uncovered that OA facilitated the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus, thereby activating the Nrf2/GPX4 pathway. Importantly, OA also upregulated the expression of FSP1, suggesting a significant and parallel protective effect against ferroptosis in EBI following SAH in synergy with GPX4. CONCLUSION: In summary, this research indicated that the PPARg activator OA augmented the neurological results in rodent models and diminished neuronal death. This neuroprotection was achieved primarily by suppressing neuronal ferroptosis. The underlying mechanism was associated with the alleviation of cellular death through the Nrf2/GPX4 and FSP1/CoQ10 pathways.

Depletion of regulatory T cells enhancing the anti-tumor effect of in situ vaccination in solid tumors.

The emergence of immune checkpoint inhibitors (ICIs) has revolutionized the clinical treatment for tumor. However, the low response rate of ICIs remains the major obstacle for curing patients and effective approaches for patients with primary or secondary resistance to ICIs remain lacking. In this study, immune stimulating agent unmethylated CG-enriched (CpG) oligodeoxynucleotide (ODN) was locally injected into the tumor to trigger a robust immune response to eradicate cancer cells, while anti-CD25 antibody was applied to remove immunosuppressive regulatory T cells, which further enhanced the host immune activity to attack tumor systematically. The combination of CpG and anti-CD25 antibody obtained notable regression in mouse melanoma model. Furthermore, rechallenge of tumor cells in the xenograft model has resulted in smaller tumor volume, which demonstrated that the combinational treatment enhanced the activity of memory T cells. Remarkably, this combinational therapy presented significant efficacy on multiple types of tumors as well and was able to prevent relapse of tumor partially. Taken together, our combinational immunotherapy provides a new avenue to enhance the clinical outcomes of patients who are insensitive or resistant to ICIs treatments.

Global trends in the burden of chronic kidney disease attributable to type 2 diabetes: An age-period-cohort analysis.

AIM: To assess temporal trends of chronic kidney disease (CKD) attributable to type 2 diabetes (T2D) globally and in five sociodemographic index (SDI) regions. MATERIALS AND METHODS: We extracted the population data and CKD burden attributable to T2D from the Global Burden of Disease Study 2019. We evaluated the trends of disability-adjusted life years (DALYs), mortality, prevalence and incidence through age-period-cohort modelling, and calculated net drifts (overall annual percentage changes), local drifts (annual percentage changes in each age group), longitudinal age curves (fitted longitudinal age-specific rates), period relative risks (RRs) and cohort RRs. RESULTS: From 1990 to 2019, the global burden of CKD attributable to T2D showed increasing trends in general. The burden of CKD attributable to T2D was highest in the middle SDI region and lowest in the low SDI region. Age effects increased with age, and peaked at the ages of 75-79 and 80-84 years for incidence and prevalence, respectively. Period RRs in the burden of CKD attributable to T2D increased, with the high SDI being the most remarkable in DALYs and mortality, and the middle SDI being the most notable in incidence. Cohort RRs showed unfavourable trends in incidence and prevalence among recent cohorts. CONCLUSIONS: After a lengthy period of multi-initiative diabetes management, the high-middle SDI region exhibited improvement. However, unresolved issues and improvement gaps were still remarkable. Future efforts to reduce the burden of CKD attributable to T2D in the population should prioritize addressing the unfavourable patterns identified.

Microbial Necromass, Lignin, and Glycoproteins for Determining and Optimizing Blue Carbon Formation.

Coastal wetlands contribute to the mitigation of climate change through the sequestration of "blue carbon". Microbial necromass, lignin, and glycoproteins (i.e., glomalin-related soil proteins (GRSP)), as important components of soil organic carbon (SOC), are sensitive to environmental change. However, their contributions to blue carbon formation and the underlying factors remain largely unresolved. To address this paucity of knowledge, we investigated their contributions to blue carbon formation along a salinity gradient in coastal marshes. Our results revealed decreasing contributions of microbial necromass and lignin to blue carbon as the salinity increased, while GRSP showed an opposite trend. Using random forest models, we showed that their contributions to SOC were dependent on microbial biomass and resource stoichiometry. In N-limited saline soils, contributions of microbial necromass to SOC decreased due to increased N-acquisition enzyme activity. Decreases in lignin contributions were linked to reduced mineral protection offered by short-range-ordered Fe (FeSRO). Partial least-squares path modeling (PLS-PM) further indicated that GRSP could increase microbial necromass and lignin formation by enhancing mineral protection. Our findings have implications for improving the accumulation of refractory and mineral-bound organic matter in coastal wetlands, considering the current scenario of heightened nutrient discharge and sea-level rise.

Nonstoichiometric Direct Arylation Polymerization of Octafluorobiphenyl with 2,7-Diiodofluorene for Regulating CH Terminals of π-Conjugated Polymer.

Nonstoichiometric direct arylation polycondensation of 2,2',3,3',5,5',6,6'-octafluorobiphenyl with excess of 2,7-diiodo-9,9-dioctyl-9H-fluorene is demonstrated. Pd/Ag dual-catalyst system under water/2-methyltetrahydrofuran biphasic conditions enables direct arylation under mild conditions and promotes the intramolecular transfer of a Pd catalyst walking through the fluorene moiety. The nonstoichiometric direct arylation polycondensation under the optimized reaction conditions produces the corresponding π-conjugated polymer with a high molecular weight and terminal octafluorobiphenyl units at both ends.

Genomic anatomy of male-specific microchromosomes in a gynogenetic fish.

Unisexual taxa are commonly considered short-lived as the absence of meiotic recombination is supposed to accumulate deleterious mutations and hinder the creation of genetic diversity. However, the gynogenetic gibel carp (Carassius gibelio) with high genetic diversity and wide ecological distribution has outlived its predicted extinction time of a strict unisexual reproduction population. Unlike other unisexual vertebrates, males associated with supernumerary microchromosomes have been observed in gibel carp, which provides a unique system to explore the rationales underlying male occurrence in unisexual lineage and evolution of unisexual reproduction. Here, we identified a massively expanded satellite DNA cluster on microchromosomes of hexaploid gibel carp via comparing with the ancestral tetraploid crucian carp (Carassius auratus). Based on the satellite cluster, we developed a method for single chromosomal fluorescence microdissection and isolated three male-specific microchromosomes in a male metaphase cell. Genomic anatomy revealed that these male-specific microchromosomes contained homologous sequences of autosomes and abundant repetitive elements. Significantly, several potential male-specific genes with transcriptional activity were identified, among which four and five genes displayed male-specific and male-biased expression in gonads, respectively, during the developmental period of sex determination. Therefore, the male-specific microchromosomes resembling common features of sex chromosomes may be the main driving force for male occurrence in gynogenetic gibel carp, which sheds new light on the evolution of unisexual reproduction.

Tris(2-ethylhexyl) phosphate induces cytotoxicity in TM3 Leydig cells by modulating autophagy and endoplasmic reticulum stress.

Tris (2-ethylhexyl) phosphate (TEHP) is a frequently used organophosphorus flame retardant with significant ecotoxicity and widespread human exposure. Recent research indicates that TEHP has reproductive toxicity. However, the precise cell mechanism is not enough understood. Here, by using testicular mesenchymal stromal TM3 cells as a model, we reveal that TEHP induces apoptosis. Then RNA sequencing analysis, immunofluorescence, and western blotting results show that THEP inhibits autophagy flux and enhances endoplasmic reticulum (ER) stress. Moreover, the activation of the ER stress is critical for TEHP-induced cell injury. Interestingly, TEHP-induced ER stress is contributed to autophagic flux inhibition. Furthermore, pharmacological inhibition of autophagy aggravates, and activation of autophagy attenuates TEHP-induced apoptosis. In summary, these findings indicate that TEHP triggers apoptosis in mouse TM3 cells through ER stress activation and autophagy flux inhibition, offering a new perspective on the mechanisms underlying TEHP-induced interstitial cytotoxicity in the mouse testis.

Nucleos(t)ide analogues altered quasispecies composition of hepatitis B virus (HBV)-resistant mutations in serum HBV DNA and serum HBV RNA.

Serum hepatitis B virus (HBV) RNA is a new serological indicator reflecting viral replication with good clinical application prospects. This study aimed to clarify the dynamic changes of serum HBV RNA levels and the quasispecies of HBV RNA virus-like particles in nucleos(t)ide analogues (NAs)-experienced chronic hepatitis B (CHB) patients harboring NAs-resistant mutations and their identifiable effects on NAs resistance. We included CHB patients who were on long-term NAs treatment and with HBV DNA rebound. The longitudinally dynamics of serum HBV RNA levels were quantitatively detected, and the quasispecies differences between serum HBV DNA and serum HBV RNA were compared by high-throughput sequencing. The effect of NAs concentration pressure on altering the resistance mutations quasispecies proportion of HBV DNA and HBV RNA in cell supernatant was analyzed in vitro. A total of 447 serum samples from 36 CHB patients treated with NAs were collected. The median follow-up period was 47 months (about 4 years), and the longest follow-up period was 117 months (about 10 years). Our results showed that HBV RNA could reflect virological breakthrough in 23 (64%, 23/36) patients, and serum HBV RNA rebound earlier than HBV DNA in 12 (52%, 12/23) patients. However, serum HBV RNA remained at a consistently high level and did not fluctuate significantly with the HBV DNA rebound in 6 of 36 patients. In addition, serum HBV RNA was not consistently detectable in 7 of the 36 patients, and their serum HBV RNA was undetectable even after HBV DNA had rebounded. The proportion of drug-resistant mutations in HBV DNA was higher than that of HBV RNA by high-throughput sequencing. The results of in vitro experiments showed that the viral strains with drug-resistant mutation in HBV DNA in cell supernatants gradually become the dominant strains with the increase of NAs concentrations. Serum HBV RNA levels can reflect virological breakthrough in most NAs- treated CHB patients, but there are certain limitations. NAs alter the quasispecies composition of serum HBV DNA and serum HBV RNA, resulting in a higher detection rate of drug-resistant mutations in serum HBV DNA than in serum HBV RNA.

Fbxo22 inhibits metastasis in triple-negative breast cancer through ubiquitin modification of KDM5A and regulation of H3K4me3 demethylation.

The importance of Fbxo22 in carcinogenesis has been highly documented. Here, we discussed downstream regulatory factors of Fbxo22 in TNBC. RNA-sequencing was conducted for identifying differentially expressed genes, followed by construction of a regulatory network. Expression patterns of Fbxo22/KDM5A in TNBC were determined by their correlation with the prognosis analyzed. Then, regulation mechanisms between Fbxo22 and KDM5A as well as between KDM5A and H3K4me3 were assayed. After silencing and overexpression experiments, the significance of Fbxo22 in repressing tumorigenesis in vitro and in vivo was explored. Fbxo22 was poorly expressed, while KDM5A was highly expressed in TNBC. Patients with elevated Fbxo22, decreased KDM5A, or higher p16 had long overall survival. Fbxo22 reduced the levels of KDM5A by ubiquitination. KDM5A promoted histone H3K4me3 demethylation to downregulate p16 expression. Fbxo22 reduced KDM5A expression to enhance p16, thus inducing DNA damage as well as reducing tumorigenesis and metastasis in TNBC. Our study validated FBXO22 as a tumor suppressor in TNBC through ubiquitination of KDM5A and regulation of p16.

Isolation and genomic characterization of a cypovirus from Clanis bilineata.

Clanis bilineata Walker, soybean hawkmoth, belongs to the subfamily Ambulicinae (Sphingidae, Lepidoptera) and is an edible insect that usually grows on soybean leaves. In this study, we isolated a new cypovirus from naturally diseased Clanis bilineata larvae (named CbCPV), scanned its structure, sequenced its genome, and studied its phylogenetic relationship to other cypoviruses. Microscopy showed that CbCPV polyhedral occlusion bodies were about 1.878 µm on average and contained many virions in the ultrathin sections. The complete genome sequence of CbCPV is 22,812 bp comprising 10 segmented double-stranded RNAs. Apart from segment 1 containing one open reading frame (ORF) and one sub-ORF, the other nine segments all contain one open reading frame and encoded one putative protein. The non-coding regions contained conserved sequences at 5' termini (AGUCAAA) and 3' termini (AGC), except segment 4 containing a different 5' termini (AUGUUUA). The whole sequence of the polyhedrin gene in CbCPV contained 892 nucleotides, encoding a protein of 246 amino acids. Based on amino acid sequences of polyhedrin or RNA dependent RNA polymerase (RdRp), the phylogenetic analysis indicated that CbCPV was closely related to DnCPV-23. The putative function of all segments differed from each other, but the most closely related species of segments were DnCPV-23 with 98.2-99.8% nucleotide identity. Overall, the evidence of morphology, protein analysis and nucleic acids (genomic pattern) showed that CbCPV is a new isolate in the cypovirus-23 type and can be termed Clanis bilineata cypovirus type 23 (CbCPV-23).

Hirsutine ameliorates myocardial ischemia-reperfusion injury through improving mitochondrial function via CaMKII pathway.

Acute myocardial infarction (AMI) is the leading cause of death worldwide. Ischemia-reperfusion (I/R) injury is considered the most common contributor to AMI. Hirsutine has been shown to protect cardiomyocytes against hypoxic injury. The present study investigated whether hirsutine improved AMI induced by I/R injury and the underlying mechanisms. In our study, we used a rat model of myocardial I/R injury. The rats were given hirsutine daily (5, 10, 20 mg/kg) by gavage for 15 days before the myocardial I/R injury. Detectable changes were observed in myocardial infarct size, mitochondrial function, histological damage, and cardiac cell apoptosis. According to our findings, hirsutine pre-treatment reduced the myocardial infarct size, enhanced cardiac function, inhibited cell apoptosis, reduced the tissue lactate dehydrogenase (LDH) and reactive oxygen species (ROS) content, as well as enhanced myocardial ATP content and mitochondrial complex activity. In addition, hirsutine balanced mitochondrial dynamics by increasing Mitofusin2 (Mfn2) expression while decreasing dynamin-related protein 1 phosphorylation (p-Drp1), which was partially regulated by ROS and calmodulin-dependent protein kinase II phosphorylation (p-CaMKII). Mechanistically, hirsutine inhibited mitochondrial-mediated apoptosis during I/R injury by blocking the AKT/ASK-1/p38 MAPK pathway. This present study provides a promising therapeutic intervention for myocardial I/R injury.

Organic pulses and bacterial invasion alleviated by the resilience of soil microbial community.

Biogas slurry is a nutrient-rich secondary product of livestock feces digestion which is recycled as a crop plantation fertilizer and provides exogenous microbes to the soil. However, the effects of biogas slurry microbes on the soil resident community remain unknown. In this study, we examined the ecological consequences of long-term biogas slurry pulse on the soil resident community and found that it promoted crop yield and altered soil characteristics. The soil microbial ecosystem was altered as a result of organic amendments due to the exogenous input of microbes and nutrients. Nevertheless, the soil resident communities were highly resilient to long-term organic pulses, as evidenced by community diversity and composition. The two dominant bacterial species in biogas slurry were Sterolibacterium and Clostridium. Notably, the abundance of Clostridium in biogas slurry increased following long-term amendments, while other species such as GP1 and Subdivision3_genera_incertae_sedis decreased; which was consistent with the results of module-eigengene analysis. Long-term organic pulses shifted the balance of microbial community assembly from stochastic to deterministic processes. Overall, our findings indicated that organic pulses accompanied with bacterial invasion could be alleviated by the resilience of soil microbial communities, thereby emphasizing the importance of microbiota assemblage and network architecture.

Biochemical mechanisms of tributyltin chloride-induced cell toxicity in Sertoli cells.

Tributyltin chloride (TBTCL) is a widely used fungicide and heat stabilizer in compositions of PVC. TBTCL has been detected in human bodies and potentially causes harmful effects on humans' thyroid, cardiovascular and other organs. As one of the first examples of endocrine disruptors, the toxicity effects of TBTCL on the male reproduction system have aroused concerns. However, the potential cellular mechanisms are not fully explored. In the current study, by using Sertoli cells, a critical regulator of spermatogenesis as a cell model, we showed that with 200 nM exposure for 24 h, TBTCL causes apoptosis and cell cycle arrest. RNA sequencing analyses suggested that TBTCL probably activates endoplasmic reticulum (ER) stress, and disrupts autophagy. Biochemical analysis showed that TBTCL indeed induces ER stress and the dysregulation of autophagy. Interestingly, activation of ER stress and inhibition of autophagy is responsible for TBTCL-induced apoptosis and cell cycle arrest. Our results thus uncovered a novel insight into the cellular mechanisms for TBTCL-induced toxicology in Sertoli cells.

Intensive management facilitates bacterial invasion on soil microbial community.

Intensive management has greatly altered natural forests, especially forests around the world are increasingly being converted into economic plantations. Soil microbiota are critical for community functions in all ecosystems, but the effects of microbial disturbance during economic plantation remain unclear. Here, we used Escherichia coli O157:H7, a model pathogenic species for bacterial invasion, to assess the invasion impacts on the soil microbial community under intensive management. The E. coli invasion was tracked for 135 days to explore the instant and legacy impacts on the resident community. Our results showed that bamboo economic plantations altered soil abiotic and biotic properties, especially increasing pH and community diversity. Higher pH in bamboo soils resulted in longer pathogen survivals than in natural hardwood soils, indicating that pathogen suppression during intensive management should arouse our attention. A longer invasion legacy effect on the resident community (P < 0.05) were found in bamboo soils underlines the need to quantify the soil resilience even when the invasion was unsuccessful. Deterministic processes drove community assembly in bamboo plantations, and this selection acted more strongly during by E. coli invasion than in hardwood soils. We also showed more associated co-occurrence patterns in bamboo plantations, suggesting more complex potential interactions within the microbial community. Apart from community structure, community functions are also strongly related to the resident species associated with invaders. These findings provide new perspectives to understand intensive management facilitates the bacterial invasion, and the impacts would leave potential risks on environmental and human health.

The Mosquito Larvicidal Activity of Lignans from Branches of Cinnamomum camphora chvar. Borneol.

The chemical investigation of branches of Cinnamomum camphora chvar. Borneol guided by mosquito larvicidal activity led to the isolation of fourteen known lignans (1-14). Their structures were elucidated unambiguously based on comprehensive spectroscopic analysis and comparison with the literature data. This is the first report of these compounds being isolated from branches of Cinnamomum camphora chvar. Borneol. Compounds 3-5 and 8-14 were isolated from this plant for the first time. All compounds isolated were subjected to anti-inflammatory, mosquito larvicidal activity and cytotoxic activity evaluation. Compounds (1-14) showed significant mosquito larvicidal activity against Culex pipiens quinquefasciatus with lethal mortality in 50% (LC50), with values ranging from 0.009 to 0.24 µg/mL. Among them, furofuran lignans(1-8) exhibited potent mosquito larvicidal activity against Cx. p. quinquefasciatus, with LC50 values of 0.009-0.021 µg/mL. From the perspective of a structure-activity relationship, compounds with a dioxolane group showed high mosquito larvicidal activity and have potential to be developed into a mosquitocide.

Talaromyces sp. Ethyl Acetate Crude Extract as Potential Mosquitocide to Control Culex pipiens quinquefasciatus.

Vector control is considered an effective approach to controlling diseases spread by mosquito bites. Entomopathogenic fungi are widely used in agriculture to control insect pests, and fungal metabolites can potentially be developed as effective mosquitocides. In this study, a high-throughput screening method was used to search for potential mosquitocides in the Global Fungal Extract Library (GFEL). We tested the larvicidal activity of 264 fungal ethyl acetate crude extracts against Culex pipiens quinquefasciatus. Nine fungal extracts caused moderate to high mortality rates (>50%), with two fungal extracts (58A7 and 101H12) causing a 100% mortality rate. The lethal concentrations for 50% of the population (LC50) were 44.27 mg/L and 31.90 mg/L, respectively. Fraction 14 had a high mortality rate, with an LC50 value of 12.13 mg/L, and was isolated from 58A7 (Fractions 1-11) and 101H12 (Fractions 12-15). Further analyses showed that Fraction 14 was made up of vermistatin and dihydrovermistatin. In a Cx. p. quinquefasciatus larvicidal bioassay, vermistatin (LC50 = 28.13 mg/L) was more toxic than dihydrovermistatin (LC50 = 83.87 mg/L). Our findings suggested that the active fungal extract 101H12 from Talaromyces sp. and its compound vermistatin could be developed as mosquitocides.

Exhaust emission inventory of typical construction machinery and its contribution to atmospheric pollutants in Chengdu, China.

To study the emission characteristics of typical construction machinery in Chengdu, 12 construction machinery (excavators, bulldozers, loaders, and forklifts) under idling mode, moving mode, and working mode, were tested using a portable emission measurement system (PEMS). Under three operating modes, the typical construction machinery in the working mode was higher in the fuel-based average emission factors of PM2.5 and NOx, while the fuel-based average emission factors of HC and CO were higher in idling mode. Integrated the results of investigation on ownership and activity levels of construction machinery, an exhaust emission inventory of typical construction machinery of Chengdu in 2018 was established according to the recommendation method. The annual emission of PM2.5, NOx, HC, and CO were 1.67 × 106, 1.61 × 108, 3.83 × 106, and 1.26 × 107 kg, respectively, and the excavator contributed the maximum emissions, accounting for an average proportion of 43.95%. The emission of construction machinery in Chengdu exhibited a clear monthly trend, with the highest from April to October and the lowest from November to March. In addition, the exhaust emissions presented an obvious spot-like characteristics, and the high-value areas were mainly concentrated in the surrounding suburban counties such as Shuangliu Wenjiang etc. To reduce pollution from construction machinery and improve the quality of the atmospheric environment, more effective measures on housing construction and municipal construction should be taken in those districts in Chengdu.

Proteomics and post-translational modifications analysis of umbilical mesenchymal stem cells aging.

Mesenchymal stem cells (MSCs) are considered to be critical for regenerative medicine. However, long-term culturing of MSCs will induce aging of MSCs, and thereafter impair cellular function. Changes in proteomics have been reported to be involved in cell aging, and therefore investigations on cell aging of MSCs at levels of proteomics and post-translational protein modifications (PTM) are ultimately important. In the present study, human umbilical cord mesenchymal stem cells (hUMSCs) were exposed to different culture conditions for either 7 or 30 days. Proteins changes during cell culture were investigated using tandem mass tag (TMT) labeling quantitative approach, and N-glycosylation patterns were analyzed using multistage mass spectrometry. We identified 66 proteins (fold change >1.50) that were differentially expressed in long-term culture. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that aging exerts a side effect on hUMSCs by affecting various molecular functions and biological processes, such as lysosome, autophagy and post-translational protein modification. Glycosylation analysis indicates that cell N-glycan patterns are associated with aging of MSCs. Our results presented here should contribute to future studies on cell aging and cellular quality controls related to MSCs as regenerative medicine.

An integration of UPLC-Q-TOF/MS and chemometrics analysis for the holistic quality evaluation of different geographical Paederia scandens.

RATIONALE: Due to the special geographical location and climate of China, there are large differences in the chemical composition and content of Paederia scandens (PS) from different origins, which will have a large impact on its efficacy. METHODS: An efficient quality control method for PS was established by combining ultra-high-performance liquid chromatography (UPLC) and electrospray ionization mass spectrometry analyses. First, a UPLC-quadrupole time-of-flight mass spectrometry system was employed to identify the chemical composition of PS from seven different origins. Then, the chemical variation in 73 batches of PS samples was subsequently investigated by quantitation of four marker compounds. RESULTS: A total of 15 common compounds were identified in the samples of PS from seven origins. And four of the marker compounds were chosen based on VIP values to characterize the differences between PS samples of different origins. The linearity ranged between 0.005 and 2.500 mg/mL; the correlation coefficients (r2 ) ranged from 0.999 to 1; the limits of detection ranged from 0.013 to 0.033 µg/mL; and the relative standard deviations for repeatability, precisions, and stabilities were below 0.2%, 1.6%, and 0.6%, respectively. CONCLUSION: The results show that the method can be effective and comprehensive in evaluating the quality of PS from different origins. And this comprehensive strategy proved to be a powerful technique used to differentiate between different geographical herbs.