Multi-omics reveals the role of MCM2 and hnRNP K phosphorylation in mouse renal aging through genomic instability.

The process of aging is characterized by structural degeneration and functional decline, as well as diminished adaptability and resistance. The aging kidney exhibits a variety of structural and functional impairments. In aging mice, thinning and graying of fur were observed, along with a significant increase in kidney indices compared to young mice. Biochemical indicators revealed elevated levels of creatinine, urea nitrogen and serum uric acid, suggesting impaired kidney function. Histological analysis unveiled glomerular enlargement and sclerosis, severe hyaline degeneration, capillary occlusion, lymphocyte infiltration, tubular and glomerular fibrosis, and increased collagen deposition. Observations under electron microscopy showed thickened basement membranes, altered foot processes, and increased mesangium and mesangial matrix. Molecular marker analysis indicated upregulation of aging-related ß-galactosidase, p16-INK4A, and the DNA damage marker γH2AX in the kidneys of aged mice. In metabolomics, a total of 62 significantly different metabolites were identified, and 10 pathways were enriched. We propose that citrulline, dopamine, and indoxyl sulfate have the potential to serve as markers of kidney damage related to aging in the future. Phosphoproteomics analysis identified 6656 phosphosites across 1555 proteins, annotated to 62 pathways, and indicated increased phosphorylation at the Ser27 site of Minichromosome maintenance complex component 2 (Mcm2) and decreased at the Ser284 site of heterogeneous nuclear ribonucleoprotein K (hnRNP K), with these modifications being confirmed by western blotting. The phosphorylation changes in these molecules may contribute to aging by affecting genome stability. Eleven common pathways were detected in both omics, including arginine biosynthesis, purine metabolism and biosynthesis of unsaturated fatty acids, etc., which are closely associated with aging and renal insufficiency.

Proteomics and ß-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice.

Aging is widely accepted as an independent risk factor for cardiovascular disease (CVD), which contributes to increasing morbidity and mortality in the elderly population. Lysine ß-hydroxybutyrylation (Kbhb) is a novel post-translational modification (PTM), wherein ß-hydroxybutyrate is covalently attached to lysine ε-amino groups. Recent studies have revealed that histone Kbhb contributes to tumor progression, diabetic cardiomyopathy progression, and postnatal heart development. However, no studies have yet reported a global analysis of Kbhb proteins in aging hearts or elucidated the mechanisms underlying this modification in the process. Herein, we conducted quantitative proteomics and Kbhb PTM omics to comprehensively elucidate the alterations of global proteome and Kbhb modification in the hearts of aged mice. The results revealed a decline in grip strength and cardiac diastolic function in 22-month-old aged mice compared to 3-month-old young mice. High-throughput liquid chromatogram-mass spectrometry analysis identified 1710 ß-hydroxybutyrylated lysine sites in 641 proteins in the cardiac tissue of young and aged mice. Additionally, 183 Kbhb sites identified in 134 proteins exhibited significant differential modification in aged hearts (fold change (FC) > 1.5 or <1/1.5, p < 0.05). Notably, the Kbhb-modified proteins were primarily detected in energy metabolism pathways, such as fatty acid elongation, glyoxylate and dicarboxylate metabolism, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, these Kbhb-modified proteins were predominantly localized in the mitochondria. The present study, for the first time, provides a global proteomic profile and Kbhb modification landscape of cardiomyocytes in aged hearts. These findings put forth novel possibilities for treating cardiac aging and aging-related CVDs by reversing abnormal Kbhb modifications.

Quantification and Proteomic Characterization of ß-Hydroxybutyrylation Modification in the Hearts of AMPKα2 Knockout Mice.

AMP-activated protein kinase alpha 2 (AMPKα2) regulates energy metabolism, protein synthesis, and glucolipid metabolism myocardial cells. Ketone bodies produced by fatty acid ß-oxidation, especially ß-hydroxybutyrate, are fatty energy-supplying substances for the heart, brain, and other organs during fasting and long-term exercise. They also regulate metabolic signaling for multiple cellular functions. Lysine ß-hydroxybutyrylation (Kbhb) is a ß-hydroxybutyrate-mediated protein posttranslational modification. Histone Kbhb has been identified in yeast, mouse, and human cells. However, whether AMPK regulates protein Kbhb is yet unclear. Hence, the present study explored the changes in proteomics and Kbhb modification omics in the hearts of AMPKα2 knockout mice using a comprehensive quantitative proteomic analysis. Based on mass spectrometry (LC-MS/MS) analysis, the number of 1181 Kbhb modified sites in 455 proteins were quantified between AMPKα2 knockout mice and wildtype mice; 244 Kbhb sites in 142 proteins decreased or increased after AMPKα2 knockout (fold change >1.5 or <1/1.5, p < 0.05). The regulation of Kbhb sites in 26 key enzymes of fatty acid degradation and tricarboxylic acid cycle was noted in AMPKα2 knockout mouse cardiomyocytes. These findings, for the first time, identified proteomic features and Kbhb modification of cardiomyocytes after AMPKα2 knockout, suggesting that AMPKα2 regulates energy metabolism by modifying protein Kbhb.

Integrated metabolomics and phosphoproteomics reveal the protective role of exosomes from human umbilical cord mesenchymal stem cells in naturally aging mouse livers.

BACKGROUND: Aging is characterized by a general decline in cellular function, which ultimately affects whole body homeostasis. This study aimed to investigate the effects and underlying mechanisms of exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-exos) on the livers of naturally aging mice. METHOD: Twenty-two-month-old C57BL6 mice were used as a natural aging animal model, divided into a saline-treated wild-type aged control group (WT-AC) and a hUCMSC-exo-treated group (WT-AEX), and then detected by morphology, metabolomics and phosphoproteomics. RESULTS: Morphological analysis showed that hUCMSC-exos ameliorated structural disorder and decreased markers of senescence and genome instability in aging livers. Metabolomics showed that hUCMSC-exos decreased the contents of saturated glycerophospholipids, palmitoyl-glycerols and eicosanoid derivatives associated with lipotoxicity and inflammation, consistent with the decreased phosphorylation of metabolic enzymes, such as propionate-CoA ligase (Acss2), at S267 detected by phosphoproteomics. Moreover, phosphoproteomics indicated that hUCMSC-exos reduced the phosphorylation of proteins participating in nuclear transport and cancer signaling, such as heat shock protein HSP90-beta (Hsp90ab1) at S226 and nucleoprotein TPR (Tpr) at S453 and S379, while increasing those involved in intracellular communication, such as calnexin (Canx) at S563 and PDZ domain-containing protein 8 (Pdzd8). Finally, phosphorylated HSP90ß and Tpr were verified predominantly in hepatocytes. CONCLUSION: HUCMSC-exos improved metabolic reprogramming and genome stability mainly associated with phosphorylated HSP90ß in hepatocytes in natural aging livers. This work provides a comprehensive resource of biological data by omics to support future investigations of hUCMSC-exos in aging.

Aquibacillus rhizosphaerae sp. nov., an Indole Acetic Acid (IAA)-producing Halotolerant Bacterium Isolated from the Rhizosphere Soil of Kalidium cuspidatum.

A bacterium (named strain LR5S19T) was isolated from the rhizosphere soil of the halophyte Kalidium cuspidatum in Baotou, Inner Mongolia, China. Strain LR5S19T was Gram-stain-positive, motile with a polar flagellum, rod shaped, and spore forming at the terminal position in swollen sporangia, and it grew at 10-40 ℃ (optimum 30 ℃), pH 6.0-9.0 (optimum pH 7.0), and in the presence of 1.0-15.0% (w/v) NaCl (optimum 2.0%). The phylogenetic analysis of the 16S rRNA gene showed that strain LR5S19T shared the highest similarity (96.7%) with A. koreensis JCM 12387T, followed by A. kalidii HU2P27T (96.2%), A. sediminis BH258T (96.1%), and 'A. salsiterrae' 3ASR75-54T (96.0%). The ANIb, AAI and dDDH values between strain LR5S19T and its closely related type strains were 69.3-73.8%, 65.4-72.4% and 19.2-20.3%, respectively. The major polar lipids in strain LR5S19T consisted of diphosphatidylglycerol, phosphatidylglycerol, and three unidentified phospholipids, while MK-7 was the major respiratory quinone. The major fatty acids of the strain were anteiso-C15:0 and iso-C15:0. Based on phylogenomic and phenotypic results, strain LR5S19T should be classified as a novel species within the genus Aquibacillus, for which Aquibacillus rhizosphaerae sp. nov. is proposed. The type strain is LR5S19T (= CGMCC 1.62028T = KCTC 43434T). The comparative genomic analysis revealed that all eight members of Aquibacillus could utilize D-glucose via the glycolysis-gluconeogenesis pathway or the pentose phosphate pathway and use the tricarboxylic acid cycle as the metabolic center. The potassium ion transport proteins and compatible solute synthesis pathways in all the members likely also help them cope with hypersaline environments.

Effects of home-based chronic wound care training for patients and caregivers: A systematic review.

We aimed to review and synthesise the evidence of the interventions of patients' and informal caregivers' engagement in managing chronic wounds at home. The research team used a systematic review methodology based on an updated guideline for reporting systematic reviews (PRISMA) and recommendations from the Synthesis Without Meta-analysis. Cochrane Central Register of Controlled Trial of the Cochrane Library, Pubmed, Embase, CINAHL, Wanfang (Chinese), and CNKI database (Chinese) were searched from inception to May 2022. The following MESH terms were used: wound healing, pressure ulcer, leg ulcer, diabetic foot, skin ulcer, surgical wound, educational, patient education, counselling, self-care, self-management, social support, and family caregiver. Experimental studies involving participants with chronic wounds (not at risk of wounds) and their informal caregivers were screened. Data were extracted and the narrative was synthesised from the findings of included studies. By screening the above databases, 790 studies were retrieved, and 16 met the inclusion and exclusion criteria. Studies were 6 RCTs and ten non-RCTs. Outcomes of chronic wound management included patient indicators, wound indicators, and family/caregiver indicators. Home-based interventions of patients or informal caregivers' engagement in managing chronic wounds at home may effectively improve patient outcomes and change wound care behaviour. What's more, educational/behavioural interventions were the primary type of intervention. Multiform integration of education and skills training on wound care and aetiology-based treatment was delivered to patients and caregivers. Besides, there are no studies entirely targeting elderly patients. Home-based chronic wound care training was important to patients with chronic wounds and their family caregivers, which may advance wound management outcomes. However, the findings of this systematic review were based on relatively small studies. We need more exploration of self and family-oriented interventions in the future, especially for older people affected by chronic wounds.

Exosomes from human umbilical cord mesenchymal stem cells protect aortas in Db/db mice characterized by combination of metabolomics and proteomics.

Diabetic cardiovascular complication is a common systemic disease with high morbidity and mortality worldwide. We hypothesise that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exos) can rescue these disorders and alleviate vascular remodeling in diabetes. Morphological, non-targeted metabolomics and 4D label-free proteomics techniques were used to analyze the aortas of db/m mice as normal control group (NCA), saline treated db/db mice (DMA), and hUCMSCs-exos treated db/db mice (DMTA), and to clarify the molecular mechanism of the protection of hUCMSCs-exos in vascular remodeling from a new point of view. The results showed that 74 metabolites were changed significantly in diabetic aortas, of which 15 were almost restored by hUCMSCs-exos. In proteomics, 30 potential targets such as Stromal cell-derived factor 2-like protein 1, Leukemia inhibitory factor receptor, Peroxisomal membrane protein and E3 ubiquitin-protein ligase MYCBP2 were detected. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based analysis showed that Central carbon metabolism in cancer and Galactose metabolism pathway were up-regulated to near normal by hUCMSCs-exos in metabolomics, with janus associated kinase-signal transducer and activator of transcription (JAK-STAT) pathway displayed in proteomics. According to bioinformatics and integrated analysis, these targeted molecules of hUCMSCs-exos to attenuate the vascular remodeling were mainly associated with regulation of energy metabolism, oxidative stress, inflammation, and cellular communications. This study provided a reference for the therapy of diabetes-induced cardiovascular complications.

Dynamic changes in maternal immune biomarkers during labor in nulliparous vs multiparous women.

BACKGROUND: Immunomodulation is observed in human parturition. However, data from longitudinal studies for the prelabor phase and the active phase of labor are lacking, and no study had compared the immune responses during labor between nulliparous and multiparous women. OBJECTIVE: This study aimed to investigate the temporal changes of immune biomarkers in maternal blood from the prelabor phase to the latent and active phases of labor and to compare the dynamic changes between nulliparous and multiparous women. STUDY DESIGN: A prospective case-control study was conducted on women who had induction of labor at term followed by vaginal delivery. Maternal blood was serially collected at 3 consecutive time points: (1) before the onset of labor, (2) during the latent phase of labor, and (3) during the active phase of labor. Peripheral immune cells were measured by 4-color flow cytometry, and the plasma concentrations of cytokines and chemokines were measured by cytometric bead arrays. A longitudinal comparison was made to assess the dynamic changes in inflammatory parameters over 3 time points in nulliparous and multiparous women, respectively, and a cross-sectional comparison was made between nulliparous and multiparous women. RESULTS: A total of 40 women, including 20 nulliparous and 20 multiparous, were included in the study. Prelabor circulating levels of macrophage inflammatory protein-1ß, monokine induced by gamma interferon, and interferon gamma-induced protein-10 were higher in multiparous women than in nulliparous women. In the latent phase of labor, the innate immune system in both groups responded with increases in neutrophils and interleukin 6, and the nulliparous women showed a more pronounced response. During the active phase of labor, such innate immune response continued with both groups, with additional increases in natural killer cells, monocyte chemoattractant protein-1, interleukin 8, and interleukin 10. Conversely, the adaptive immune system in nulliparous women showed a reduction in both cytotoxic and helper T cells, whereas the adaptive immune system in multiparous women only had a reduction in helper T cells, showing a smaller reduction. CONCLUSION: Innate and adaptive immune responses partake in immunomodulation during human parturition. Nulliparous and multiparous women showed different responses in their blood levels of immune cells and biomarkers during the different phases of labor.

Health-related quality of life in different trimesters during pregnancy.

BACKGROUND: Pregnant women experience physical, physiological, and mental changes. Health-related quality of life (HRQoL) is a relevant indicator of psychological and physical behaviours, changing over the course of pregnancy. This study aims to assess HRQoL of pregnant women during different stages of pregnancy. METHODS: This cross-sectional study was performed using the The EuroQoL Group's five-dimension five-level questionnaire (EQ-5D-5L) to assess the HRQoL of pregnant women, and demographic data were collected. This study was conducted in a regional university hospital in Guangzhou, China. RESULTS: A total of 908 pregnant women were included in this study. Pregnant women in the early 2nd trimester had the highest HRQoL. The HRQoL of pregnant women rose from the 1st trimester to the early 2nd trimester, and dropped to the bottom at the late 3rd trimester due to some physical and mental changes. Reports of pain/discomfort problem were the most common (46.0%) while self-care were the least concern. More than 10% of pregnant women in the 1st trimester had health-related problems in at least one dimension of whole five dimensions. In the whole sample, the EuroQoL Group's visual analog scale (EQ-VAS) was 87.86 ± 9.16. Across the gestational stages, the HRQoL remained stable during the pregnancy but the highest value was observed in the 1st trimester (89.65 ± 10.13) while the lowest was in the late 3rd trimester (87.28 ± 9.13). CONCLUSIONS: During pregnancy, HRQoL were associated with gestational trimesters in a certain degree. HRQoL was the highest in the early 2nd trimester and then decreased to the lowest in the late 3rd trimester due to a series of physical and psychological changes. Therefore, obstetric doctors and medical institutions should give more attention and care to pregnant women in the late 3rd trimester.

The relationship between total cholesterol and postpartum impaired glucose tolerance in women with gestational diabetes mellitus.

BACKGROUND: History of gestational diabetes mellitus (GDM) and serum lipid abnormalities were associated with postpartum impaired glucose tolerance. To investigate the association between concentration of total cholesterol (TC), at the time of GDM diagnosis, and risk of postpartum glucose intolerance. METHODS: Women who were diagnosed GDM with a live singleton delivery between January 1, 2013 and December 31, 2017 were included. Women were grouped based on the TC quartiles at the time of GDM diagnosis and had an OGTT at 6-12 weeks after delivery. The relationship between TC and the risk of postpartum glucose intolerance was assessed by COX regression. RESULTS: A total of 845 women were in the final analysis. Higher TC quartile at diagnosis of GDM was associated with a decreased risk of postpartum glucose intolerance. Women in the highest TC quartile (>7.0 mmol L- 1) had approximately only half-risk of any postpartum glucose intolerance, compared with women in the lowest TC quartile (<5.5 mmol L- 1). CONCLUSIONS: The decreased concentration of TC, at the time of GDM diagnosis, was related to an increased risk of postpartum abnormal glucose regulation in GDM women. Therefore, because both excessively increased and decreased TC were associated with pregnancy and postpartum complications, the optimal concentration of maternal TC throughout pregnancy remained to be further researched.

Health-related quality of life in pregnancy with uterine fibroid: a cross-sectional study in China.

BACKGROUND: Uterine fibroids (UFs) are the most common benign tumors in women. They are likely to cause numerous clinical symptoms, such as pain, menorrhagia, and other obstetric complications in pregnant women. This study aimed to determine the health-related quality of life (HRQoL) during pregnancy with uterine fibroids (UF), thus providing a utility-based case value in pregnant women with UF and understanding of whether HRQoL is associated with clinical outcomes in pregnant women with UFs. METHOD: This study was conducted in a cross-sectional manner. This study was based on questionnaire surveys completed by sequential out- and in-patients and was conducted in a regional university hospital in Guangzhou, China. The EuroQoL five-dimension-five-level (EQ-5D-5 L) questionnaire was used, and demographic data were collected. An electronic record of the clinical outcomes of pregnant women with UF was retrieved from the hospital's electronic medical record system. The association between UF and HRQoL was evaluated by ordered regression. RESULTS: Seven-hundred-sixty-seven pregnant women with a mean age (SD) of 32.7 (4.8) years completed 707 questionnaires. Overall, when comparing the UF with non-UF groups, we detected statistical differences in age, body mass index (BMI), gravidity and abortion times, partner's smoking and alcoholic habits, advanced maternal age, and uterine scars (p <  0.05). Furthermore, pregnant women without UF scored significantly higher than those with UF on the EQ-5D value system (0.84 versus 0.79; p = 0.017). Moreover, pregnant women with UF suffered more health-related problems, especially with respect to self-care (odds ratio [OR] = 3.69, p <  0.01) and usual activity dimensions (OR = 2.11; p = 0.01). CONCLUSION: We found that UF has a negative impact on the HRQoL of pregnant women with respect to self-care and usual activity dimensions. Also, the EQ-5D score was a better index than the EQ-VAS score for HRQoL when evaluating of the QoL of our population of pregnant women.

The effect of exercise during pregnancy on gestational diabetes mellitus in normal-weight women: a systematic review and meta-analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy, and it has both short- and long-term adverse effects on the health of mothers and fetuses. To investigate the effect of exercise during pregnancy on the occurrence of GDM among normal-weight pregnant women. METHODS: We searched for studies published between January 1994 and June 2017 that appeared in the Web of Science, Scopus, ClinicalTrials.gov or Cochrane library databases. Randomized controlled trials that investigated the preventive effect of exercise on GDM in normal-weight women were included. Interventions including any confounding factors (e.g., dietary) were excluded. We extracted maternal characteristics, the diagnostic criteria of GDM, and basic information for intervention and obstetric outcomes. The primary outcome was the occurrence of GDM, and the secondary outcomes included gestational weight gain, gestational age at birth, birth weight, and the odds of cesarean section. A meta-analysis was conducted based on calculations of pooled estimates using the random-effects model. RESULTS: Eight studies were included in this systematic review and meta-analysis. Exercise during pregnancy was shown to decrease the occurrence of GDM [RR = 0.58, 95% CI (0.37, 0.90), P = 0.01 and RR = 0.60, 95% CI (0.36, 0.98), P = 0.04 based on different diagnosis criteria, respectively] in normal-weight women. Regarding secondary outcomes, exercise during pregnancy can decrease gestational weight gain [MD = - 1.61, 95% CI (- 1.99, - 1.22), P<0.01], and  had no significant effects on gestational age at birth [MD = - 0.55, 95% CI (- 1.57, 0.47), P = 0.29], birth weight [MD = - 18.70, 95% CI (- 52.49, 15.08), P = 0.28], and the odds of caesarean section [RR = 0.88, 95% CI (0.72, 1.08), P = 0.21], respectively. CONCLUSIONS: Exercise during pregnancy can ostensibly decrease the occurrence of GDM without reducing gestational age at delivery and increasing the odds of cesarean section in normal-weight women.

The impact on ovarian reserve of haemostasis by bipolar coagulation versus suture following surgical stripping of ovarian endometrioma: a meta-analysis.

Concern is increasing that the use of bipolar coagulation or suturing to obtain haemostasis after surgical stripping of ovarian endometrioma could affect ovarian reserve. To compare the ovarian damage associated with the use of bipolar coagulation with ovarian suture as determined by anti-Müllerian hormone (AMH), FSH and antral follicle count, 21 studies were identified. Pooled analysis of 312 patients showed the average serum level of AMH was lower in the coagulation group than in the suture group (3-month follow-up: weighted mean difference (WMD) -0.75 ng/ml, 95% confidence interval (CI) -1.82 to 0.31; 6 months: WMD -1.45 ng/ml, 95% CI -2.43 to -0.47; 12 months: WMD -1.01 ng/ml; 95% CI -1.85 to -0.17), although heterogeneity was high. The weighted overall average levels of FSH between the two groups were not statistically significantly different 3 months after surgery (WMD 0.37 mIU/ml; 95% CI -1.56 to 1.30). The mean antral follicle count in the coagulation group was significantly less than in the suture group at 3 months' follow-up (WMD -2.53, with 95% CI -4.94 to -0.12). This study showed bipolar coagulation did more harm to the ovarian reserve than the suture haemostasis during excision of ovarian cyst as shown by a significant postoperative reduction in AMH.

LRG1 is an independent prognostic factor for endometrial carcinoma.

Endometrial cancer (EC) is one of the most common female malignancies. The patients with high-risk factors may have poor prognosis. Therefore, there is an urgent need to find a new molecule to more accurately predict survival of patients. Leucine-rich-alpha-2-glycoprotein1 (LRG1), one of leucine-rich repeat family, was closely associated with cancer metastasis and poor prognosis. The biological functions and the expression level of LRG1 remain obscure in EC. In this study, by immunohistochemical analysis of 242 EC patient tissues, we found that LRG1 expression was associated with stage and lymphatic metastasis in both test cohort (133 patients) and validation cohort (109 patients). Furthermore, to investigate the prognostic value of LRG1 in endometrial carcinoma, we analyzed the correlation between variables and overall survival with Cox proportional hazard regression. The result showed that LRG1 was an independent prognostic factor for overall survival of endometrial carcinoma patients. To further evaluate the prognostic efficiency of LRG1 in endometrial carcinoma, we compared the sensitivity and specificity of LRG1 in endometrial carcinoma prognosis by logistic regression. The result showed that LRG1 combining with other clinicopathological risk factors was a stronger prognostic model than clinicopathological risk factors alone or their combination. Thus, LRG1 potentially offered clinical value in directing personal treatment for endometrial carcinoma patients.

One-step separation and purification of two chromones and one pyrone from Aloe barbadensis Miller: a comparison between reversed-phase flash chromatography and high-speed counter current chromatography.

INTRODUCTION: Chromones and pyrones are the major secondary metabolites of Aloe barbadensis Miller. As they are minor components of the plant, an efficient purification procedure for them is of great importance for promoting their pharmacological studies. OBJECTIVE: To develop efficient methods for one-step separation and purification of two chromones (5-((S)-2'-oxo-4'-hydroxypentyl)-2-hydroxymethylchromone (1) and 5-((4E)-2'-oxo-pentenyl)-2-hydroxymethylchromone (3)) and one pyrone (aloenin aglycone (2)) from A. barbadensis via reversed-phase flash chromatography (RP-FC) and high-speed counter current chromatography (HSCCC). METHODS: The RP-FC separation was performed using methanol:water (26:74, v/v) as the mobile phase at a flow rate of 20 mL/min. A solvent system composed of dichloromethane:methanol:water (3:1.5:1, v/v/v) was used for the HSCCC separation, at a flow rate of 2.0 mL/min. RESULTS: A one-step RP-FC operation within 110 min was successfully used for the purification of compounds 1 (27.9 mg, 96.5%), 2 (32.4 mg, 98.2%) and 3 (4.1 mg, 99.0%) from 129 mg of crude sample, and a one-step HSCCC separation within 95 min was successfully implemented for the purification of compounds 1 (31.1 mg, 97.6%), 2 (35.8 mg, 96.7%) and 3 (2.7 mg, 98.1%) from 134 mg of crude sample. CONCLUSION: The developed procedures were efficient, with low cost and high yield, which would afford sufficient amounts of high-purity compounds for chromatographic purposes and pharmacological activity screening.

Causal association between lipid-lowering drugs and cancers: A drug target Mendelian randomization study.

Accumulating evidences have indicated that lipid-lowering drugs have effect for the treatment of cancers. However, causal associations between lipid-lowering drugs and the risk of cancers are still unclear. In our study, we utilized single nucleotide polymorphisms of proprotein convertase subtilis kexin 9 (PCSK9) inhibitors and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors and performed a drug target Mendelian randomization to explore the causal association between lipid-lowering drugs and the risk of cancers. Five regression methods were carried out, including inverse variance weighted (IVW) method, MR Egger, weighted median, simple mode and weighted mode methods, of which IVW method was considered as the main analysis. Our outcome dataset contained the risk of breast cancer (BC), colorectal cancer, endometrial cancer, gastric cancer (GC), hepatocellular carcinoma (HCC), lung cancer, esophageal cancer, prostate cancer (PC), and skin cancer (SC). Our results demonstrated that PCSK9 inhibitors were significant associated with a decreased effect of GC [IVW: OR = 0.482, 95% CI: 0.264-0.879, P = .017]. Besides, genetic inhibitions of HMGCR were significant correlated with an increased effect of BC [IVW: OR = 1.421, 95% CI: 1.056-1.911, P = .020], PC [IVW: OR = 1.617, 95% CI: 1.234-2.120, P = .0005] and SC [IVW: OR = 1.266, 95% CI: 1.022-1.569, P = .031]. For GC [IVW: OR = 0.559, 95% CI: 0.382-0.820, P = .0029] and HCC [IVW: OR = 0.241, 95% CI: 0.085-0.686, P = .0077], HMGCR inhibitors had a protective risk. Our method suggested that PCSK9 inhibitors were significant associated with a protective effect of GC. Genetic inhibitions of HMGCR were significant correlated with an increased effect of BC, PC and SC. Meanwhile, HMGCR inhibitors had a protective risk of GC and HCC. Subsequent studies still needed to assess potential effects between lipid-lowering drugs and the risk of cancers with clinical trials.

A comprehensive comparative genomic analysis revealed that plant growth promoting traits are ubiquitous in strains of Stenotrophomonas.

Stenotrophomonas strains, which are often described as plant growth promoting (PGP) bacteria, are ubiquitous in many environments. A total of 213 genomes of strains of Stenotrophomonas were analyzed using comparative genomics to better understand the ecological roles of these bacteria in the environment. The pan-genome of the 213 strains of Stenotrophomonas consists of 27,186 gene families, including 710 core gene families, 11,039 unique genes and 15,437 accessory genes. Nearly all strains of Stenotrophomonas harbor the genes for GH3-family cellulose degradation and GH2- and GH31-family hemicellulose hydrolase, as well as intact glycolysis and tricarboxylic acid cycle pathways. These abilities suggest that the strains of this genus can easily obtain carbon and energy from the environment. The Stenotrophomonas strains can respond to oxidative stress by synthesizing catalase, superoxide dismutase, methionine sulfoxide reductase, and disulfide isomerase, as well as managing their osmotic balance by accumulating potassium and synthesizing compatible solutes, such as betaine, trehalose, glutamate, and proline. Each Stenotrophomonas strain also contains many genes for resistance to antibiotics and heavy metals. These genes that mediate stress tolerance increase the ability of Stenotrophomonas strains to survive in extreme environments. In addition, many functional genes related to attachment and plant colonization, growth promotion and biocontrol were identified. In detail, the genes associated with flagellar assembly, motility, chemotaxis and biofilm formation enable the strains of Stenotrophomonas to effectively colonize host plants. The presence of genes for phosphate-solubilization and siderophore production and the polyamine, indole-3-acetic acid, and cytokinin biosynthetic pathways confer the ability to promote plant growth. These strains can produce antimicrobial compounds, chitinases, lipases and proteases. Each Stenotrophomonas genome contained 1-9 prophages and 17-60 genomic islands, and the genes related to antibiotic and heavy metal resistance and the biosynthesis of polyamines, indole-3-acetic acid, and cytokinin may be acquired by horizontal gene transfer. This study demonstrates that strains of Stenotrophomonas are highly adaptable for different environments and have strong potential for use as plant growth-promoting bacteria.

NRhFluors: Quantitative Revealing the Interaction between Protein Homeostasis and Mitochondria Dysfunction via Fluorescence Lifetime Imaging.

Degenerative diseases are closely related to the changes of protein conformation beyond the steady state. The development of feasible tools for quantitative detection of changes in the cellular environment is crucial for investigating the process of protein conformational variations. Here, we have developed a near-infrared AIE probe based on the rhodamine fluorophore, which exhibits dual responses of fluorescence intensity and lifetime to local viscosity changes. Notably, computational analysis reveals that NRhFluors fluorescence activation is due to inhibition of the RACI mechanism in viscous environment. In the chemical regulation of rhodamine fluorophores, we found that variations of electron density distribution can effectively regulate CI states and achieve fluorescence sensitivity of NRhFluors. In addition, combined with the AggTag method, the lifetime of probe A9-Halo exhibits a positive correlation with viscosity changes. This analytical capacity allows us to quantitatively monitor protein conformational changes using fluorescence lifetime imaging (FLIM) and demonstrate that mitochondrial dysfunction leads to reduced protein expression in HEK293 cells. In summary, this work developed a set of near-infrared AIE probes activated by the RACI mechanism, which can quantitatively detect cell viscosity and protein aggregation formation, providing a versatile tool for exploring disease-related biological processes and therapeutic approaches.

Causal relationships between gut microbrome and digestive system diseases: A two-sample Mendelian randomization study.

Growing evidences of recent studies have shown that gut microbrome are causally related to digestive system diseases (DSDs). However, causal relationships between the gut microbiota and the risk of DSDs still remain unclear. We utilized identified gut microbiota based on class, family, genus, order and phylum information and digestive system diseases genome-wide association study (GWAS) dataset for two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used to evaluate causal relationships between gut microbiota and 7 DSDs, including chronic gastritis, colorectal cancer, Crohn's disease, gastric cancer, gastric ulcer, irritable bowel syndrome and esophageal cancer. Finally, we verified the robustness of MR results based on heterogeneity and pleiotropy analysis. We discovered 15 causal associations with genetic liabilities in the gut microbiota and DSDs, such as genus Victivallis, genus RuminococcaceaeUCG005, genus Ruminococcusgauvreauiigroup, genus Oxalobacter and so on. Our MR analysis revealed that the gut microbiota is causally associated with DSDs. Further researches of the gut microbiota and the pathogenesis of DSDs are still significant and provide new methods for the prevention and treatment of DSDs.

Mobile-based ecological momentary assessment and intervention: bibliometric analysis.

Objective: The aim of this article was to review existing documents in the field of mobile-based EMA and EMI, provide an overview of current hot topics, and predict future development trends. Methods: We conducted a bibliometric study on mobile-based EMA and EMI publications that were collected from the Web of Science Core Collection database. Biblioshiny and CiteSpace were utilized to analyze scientific productions, leading sources, authors, affiliations, documents, research hot topics, keywords, and trend topics. Results: A total of 2222 documents related to EMA and EMI published between 1992 and 2023 were retrieved. In recent years, scholarly publications have generally increased in mobile-based EMA and EMI research, particularly in the last decade. JMIR mHealth and uHealth (n=86), as well as JMIR (n=73), showed the highest number of publications. The United States (n=1038), Germany (n=218) and Netherlands (n=175) were leading countries. Regarding keyword co-occurrence and trend topics analysis, mental health, health behaviors, and feasibility were hot topics in mobile-based EMA and EMI research. Future research trends included using EMA for tailoring EMI, just-in-time adaptive interventions (JITAI), and digital phenotyping. Conclusion: This bibliometric study on mobile-based EMA and EMI is a valuable resource for understanding the field's evolution and future trends. Our analysis indicates that EMA and EMI have great potential in health behaviors and mental health, but implementation should consider feasibility and reactivity issues carefully. Emerging trends include EMA-tailored EMI, JITAI, and digital phenotyping. In the future, strengthening multidisciplinary cooperation will be necessary to promote the continued development of the field.