Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes.

While rapid demographic changes in Asia are driving the incidence of chronic aging-related diseases, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun-metagenomic sequencing for high-resolution taxonomic and functional characterization of their gut microbiomes (n = 234). Joint species-level analysis with other Asian cohorts identified distinct age-associated shifts characterized by reduction in microbial richness, and specific Alistipes and Bacteroides species enrichment (e.g., Alistipes shahii and Bacteroides xylanisolvens). Functional analysis confirmed these changes correspond to metabolic potential expansion in aging towards alternate pathways synthesizing and utilizing amino-acid precursors, vis-à-vis dominant microbial guilds producing butyrate in gut from pyruvate (e.g., Faecalibacterium prausnitzii, Roseburia inulinivorans). Extending these observations to key clinical markers helped identify >10 robust microbial associations to inflammation, cardiometabolic and liver health, including potential probiotic species (e.g., Parabacteroides goldsteinii) and pathobionts (e.g., Klebsiella pneumoniae), highlighting the microbiome's role as biomarkers and potential targets for promoting healthy aging.

Polyprenylated acylphloroglucinols from Hypericum sampsonii with cytotoxicity against pancreatic carcinomas.

Chemical investigation on the 80% EtOH extract of the air dried aerial parts of Hypericum sampsonii resulted in the isolation of two new polycyclic polyprenylated derivatives, hypersampines A and B (1 and 2). The structures of the new compounds were elucidated by spectroscopic data (NMR, IR, and UV) and high resolution mass analysis. The two isolated polyprenylated acylphloroglucinols were tested in vitro for cytotoxic activities against 6 pancreatic cell lines. As a result, compounds 1 and 2 possessed modest cytotoxic activities against all the tested tumor cell lines with IC50 values less than 40 µM.

Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine.

Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.

Exopolysaccharides of Paenibacillus polymyxa: A review.

Paenibacillus polymyxa (P. polymyxa) is a member of the genus Paenibacillus, which is a rod-shaped, spore-forming gram-positive bacterium. P. polymyxa is a source of many metabolically active substances, including polypeptides, volatile organic compounds, phytohormone, hydrolytic enzymes, exopolysaccharide (EPS), etc. Due to the wide range of compounds that it produces, P. polymyxa has been extensively studied as a plant growth promoting bacterium which provides a direct benefit to plants through the improvement of N fixation from the atmosphere and enhancement of the solubilization of phosphorus and the uptake of iron in the soil, and phytohormones production. Among the metabolites from P. polymyxa, EPS exhibits many activities, for example, antioxidant, immunomodulating, anti-tumor and many others. EPS has various applications in food, agriculture, environmental protection. Particularly, in the field of sustainable agriculture, P. polymyxa EPS can be served as a biofilm to colonize microbes, and also can act as a nutrient sink on the roots of plants in the rhizosphere. Therefore, this paper would provide a comprehensive review of the advancements of diverse aspects of EPS from P. polymyxa, including the production, extraction, structure, biosynthesis, bioactivity and applications, etc. It would provide a direction for future research on P. polymyxa EPS.

Prediction of pathological complete response of breast cancer patients who received neoadjuvant chemotherapy with a nomogram based on clinicopathologic variables, ultrasound, and MRI.

OBJECTIVE: To establish a nomogram for predicting the pathologic complete response (pCR) in breast cancer (BC) patients after NAC by applying magnetic resonance imaging (MRI) and ultrasound (US). METHODS: A total of 607 LABC women who underwent NAC before surgery between January 2016 and June 2022 were retrospectively enrolled, and then were randomly divided into the training (n = 425) and test set (n = 182) with the ratio of 7:3. MRI and US variables were collected before and after NAC, as well as the clinicopathologic features. Univariate and multivariate logistic regression analyses were applied to confirm the potentially associated predictors of pCR. Finally, a nomogram was developed in the training set with its performance evaluated by the area under the receiver operating characteristics curve (ROC) and validated in the test set. RESULTS: Of the 607 patients, 108 (25.4%) achieved pCR. Hormone receptor negativity (odds ratio [OR], 0.3; P < .001), human epidermal growth factor receptor 2 positivity (OR, 2.7; P = .001), small tumour size at post-NAC US (OR, 1.0; P = .031), tumour size reduction ≥50% at MRI (OR, 9.8; P < .001), absence of enhancement in the tumour bed at post-NAC MRI (OR, 8.1; P = .003), and the increase of ADC value after NAC (OR, 0.3; P = .035) were all significantly associated with pCR. Incorporating the above variables, the nomogram showed a satisfactory performance with an AUC of 0.884. CONCLUSION: A nomogram including clinicopathologic variables and MRI and US characteristics shows preferable performance in predicting pCR. ADVANCES IN KNOWLEDGE: A nomogram incorporating MRI and US with clinicopathologic variables was developed to provide a brief and concise approach in predicting pCR to assist clinicians in making treatment decisions early.

Inhibition of EphA4 reduces vasogenic edema after experimental stroke in mice by protecting the blood-brain barrier integrity.

Cerebral vasogenic edema, a severe complication of ischemic stroke, aggravates neurological deficits. However, therapeutics to reduce cerebral edema still represent a significant unmet medical need. Brain microvascular endothelial cells (BMECs), vital for maintaining the blood-brain barrier (BBB), represent the first defense barrier for vasogenic edema. Here, we analyzed the proteomic profiles of the cultured mouse BMECs during oxygen-glucose deprivation and reperfusion (OGD/R). Besides the extensively altered cytoskeletal proteins, ephrin type-A receptor 4 (EphA4) expressions and its activated phosphorylated form p-EphA4 were significantly increased. Blocking EphA4 using EphA4-Fc, a specific and well-tolerated inhibitor shown in our ongoing human phase I trial, effectively reduced OGD/R-induced BMECs contraction and tight junction damage. EphA4-Fc did not protect OGD/R-induced neuronal and astrocytic death. However, administration of EphA4-Fc, before or after the onset of transient middle cerebral artery occlusion (tMCAO), reduced brain edema by about 50%, leading to improved neurological function recovery. The BBB permeability test also confirmed that cerebral BBB integrity was well maintained in tMCAO brains treated with EphA4-Fc. Therefore, EphA4 was critical in signaling BMECs-mediated BBB breakdown and vasogenic edema during cerebral ischemia. EphA4-Fc is promising for the treatment of clinical post-stroke edema.

Progress of proximity labeling technology in membrane protein interaction / 中国药科大学学报

@#Abstract: Membrane proteins, which play a critical role in various life processes, particularly in regulating cell-cell contact and signal transduction, are closely linked to cell differentiation and maturation. Therefore, it is of great theoretical and practical significance to develop a variety of methods to thoroughly explore the interactions between membrane proteins. In addition to traditional techniques such as immunoprecipitation, newly developed proximity labeling (PL) techniques have gradually become important means to study membrane protein interaction. PL methods are based on engineered enzymes fused with bait protein to catalyze small molecules, label neighboring target proteins, and detect the interactions by flow cytometry, mass spectrometry, confocal microscopic imaging, etc. This paper focuses on the recent developments in PL techniques for studying membrane protein interactions, with a prospect of the potential future directions for research in this area.

Effects of Tuina on motor behavior,oxidative stress and inflammatory response in rats with chronic fatigue syndrome / 中国运动医学杂志

Objective To explore the effect of back Tuina on motor behavior,oxidative stress and in-flammation in rats with chronic fatigue syndrome(CFS).Methods Twenty-four Sprague-Dawley rats were randomly divided into a blank group,a model group and a Tuina group,each of 8,according to a random number table.The CFS rat model was prepared by means of forced weight-bearing swimming combined with chronic stress stimulation in 21 days.After modeling,the Tuina group was given daily 20-minute Tuina for 14 days.The general condition semi-quantitative score,exhaustion swimming time and open field experiment(OFE)distance of all groups were recorded.After the experiment,sam-ples were collected,and the histopathological changes of the vertical spine muscles were observed by hematoxylin and eosin(HE)staining.The cross-sectional area and diameter of muscle fibers were calcu-lated using Image Pro Plus software,and the frequency distribution diagram of cross-sectional area of muscle fibers was processed by using the Origin software.The contents of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and peroxisome proliferator-activated receptor γ-coactivator 1α(PGC-1α)and tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6 in the serum of rats were mea-sured.Results After the intervention,the general condition semi-quantitative score of the Tuina group was significantly lower than the model group(P<0.01),while the exhaustion swimming time and OFE distance were significantly higher than the latter group(P<0.05,P<0.01).(2)HE staining showed that the significant atrophy of erector spinal muscle cells in the model group,was significantly relieved in the Tuina group.(3)Compared with the blank group,the contents of SOD,GSH-Px and PGC-1α in erectus muscles decreased significantly(P<0.01),while those of TNF-α,IL-1β and IL-6 in the se-rum of the model group increased significantly(P<0.01).However,compared with model group,the contents of SOD,GSH-Px and PGC-1α in erectus muscle increased significantly(P<0.05,P<0.01),while those of TNF-α,IL-1β and IL-6 of the Tuina group decreased significantly(P<0.05,P<0.01).Conclusion Tuina in the back can regulate the oxidative stress response,reliever the inflammatory re-sponse and improve the motor behavior of CFS rats.

Joint effects of gas bubbles and solid particles on sonochemical inhibition in sonicated aqueous solutions.

Wastewater is a multicomponent and multiphase mixture. Gas bubbles and solid particles in the dispersed phase influence sonochemical efficiency during ultrasonic treatment of wastewater, sometimes unfavorably; however, the influencing factors and mechanisms remain unclear. In this paper, the influence of argon gas bubbles (1.2 mm) and monodisperse silica particles (0.1 mm) on sonochemical effects in an aqueous system using a horn-type reactor (20 kHz) is reported. Triiodide formation decreased with an increase in the volume fraction of either or both phases. The two phases started inhibiting sonoreactions as the total volume fraction approached 3.0-4.0 vol% compared to pure water. The effect of the gas-to-solid ratio is also considered. We propose an acoustic attenuation model, which incorporates the scattering effect of solid particles and the thermal effect of gas bubbles. The agreement between the modeling and experimental results demonstrates that the two phases are jointly responsible for sonochemical inhibition by increasing ultrasound attenuation. This enhances the understanding of sonochemistry in gas-solid-liquid systems and helps regulate gases and solids in sonochemical reactors.

Nogo-B mediates endothelial oxidative stress and inflammation to promote coronary atherosclerosis in pressure-overloaded mouse hearts.

AIMS: Endothelial dysfunction plays a pivotal role in atherosclerosis, but the detailed mechanism remains incomplete understood. Nogo-B is an endoplasmic reticulum (ER)-localized protein mediating ER-mitochondrial morphology. We previously showed endothelial Nogo-B as a key regulator of endothelial function in the setting of hypertension. Here, we aim to further assess the role of Nogo-B in coronary atherosclerosis in ApoE-/- mice with pressure overload. METHODS AND RESULTS: We generated double knockout (DKO) mouse models of systemically or endothelium-specifically excising Nogo-A/B gene on an ApoE-/- background. After 7 weeks of transverse aortic constriction (TAC) surgery, compared to ApoE-/- mice DKO mice were resistant to the development of coronary atherosclerotic lesions and plaque rapture. Sustained elevation of Nogo-B and adhesion molecules (VCAM-1/ICAM-1), early markers of atherosclerosis, was identified in heart tissues and endothelial cells (ECs) isolated from TAC ApoE-/- mice, changes that were significantly repressed by Nogo-B deficiency. In cultured human umbilical vein endothelial cells (HUVECs) exposure to inflammatory cytokines (TNF-α, IL-1ß), Nogo-B was upregulated and activated reactive oxide species (ROS)-p38-p65 signaling axis. Mitofusin 2 (Mfn2) is a key protein tethering ER to mitochondria in ECs, and we showed that Nogo-B expression positively correlated with Mfn2 protein level. And Nogo-B deletion in ECs or in ApoE-/- mice reduced Mfn2 protein content and increased ER-mitochondria distance, reduced ER-mitochondrial Ca2+ transport and mitochondrial ROS generation, and prevented VCAM-1/ICAM-1 upregulation and EC dysfunction, eventually restrained atherosclerotic lesions development. CONCLUSION: Our study revealed that Nogo-B is a critical modulator in promoting endothelial dysfunction and consequent pathogenesis of coronary atherosclerosis in pressure overloaded hearts of ApoE-/- mice. Nogo-B may hold the promise to be a common therapeutic target in the setting of hypertension.

Effects of plastic contamination on carbon fluxes in a subtropical coastal wetland of East China.

Coastal wetlands are recognized as carbon sinks that play an important role in mitigating global climate change because of the strong carbon uptake by vegetation and high carbon sequestration in the soil. Over the last few decades, plastic waste pollution in coastal zones has become increasingly serious owing to high-intensity anthropogenic activities. However, the influence of plastic waste (including foam waste) accumulation in coastal wetlands on carbon flux remains unclear. In the Yangtze Estuary, we investigated the variabilities of vegetation growth, carbon dioxide (CO2) and methane (CH4) fluxes, and soil properties in a clean Phragmites australis marsh and mudflat and a plastic-polluted marsh during summer and autumn. The clean marsh showed a strong CO2 uptake capacity (a carbon sink), and the clean mudflat showed a weak CO2 sink during the measurement period. However, polluted marshes are a significant source of CO2 emissions. Regardless of the season, the gross primary production and vegetation biomass of the polluted marshes were on average 9.5 and 1.1 times lower than those in the clean marshes, respectively. Ecosystem respiration and CH4 emissions in polluted marshes were significantly higher than those in clean marshes and mudflats. Generally, the soil bulk density and salinity in polluted marshes were lower, whereas the median particle size was higher at the polluted sites than at the clean sites. Increased soil porosity and decreased salinity may favor CO2 and CH4 emissions through gas diffusion pathways and microbiological behavior. Moreover, the concentrations of heavy metals in the soil of plastic-polluted marshes were 1.24-1.49 times higher than those in the clean marshes, which probably limited vegetation growth and CO2 uptake. Our study highlights the adverse effects of plastic pollution on the carbon sink functions of coastal ecosystems, which should receive global attention in coastal environmental management.

Effects of fibre-supplemented enteral feeds on bowel function of non-critically ill tube-fed adults: a meta-analysis of randomised controlled trials.

Diarrhoea is common in enterally fed patients and can impact their nutritional and overall outcomes. This meta-analysis evaluates the potential benefits of fibre-supplemented (FS) feeds on incidence of diarrhoea and stool frequency in non-critically ill tube-fed adults. Databases including PubMed, Embase and CINAHL with full text were searched for randomised controlled trials (RCT) with adults on exclusive tube feeding, published until August 2022. The Cochrane Collaboration's tool was used for quality assessment. Studies with published results on incidence of diarrhoea and stool frequency were analysed using RevMan 5. Thirteen RCT with 847 non-critically ill patients between 20 and 90 years old without diarrhoea at the onset of enteral feeding were included. Study duration ranged from 3 to 35 d. Nine papers investigated the incidence of diarrhoea where intervention group was given FS and control was given non-fibre-supplemented (NFS) enteral feeds. Those receiving FS feeds were significantly less likely to experience diarrhoea as compared with those using NFS feeds (OR 0·44; 95 % CI 0·20, 0·95; P = 0·04; I2 = 71 %). Combined analysis showed no differences in stool frequency in those receiving NFS feeds (SMD 0·32; 95 % CI -0·53, 1·16; P = 0·47; I2 = 90 %). Results should be interpreted with caution due to considerable heterogeneity between study population, assessment tool for diarrhoea, potential conflict of interest and short duration of studies. This meta-analysis shows that FS feeds can reduce the incidence of diarrhoea in non-critically ill adults; however, the effects of stool frequency remain debatable.

Regio-controllable [2+2] benzannulation with two adjacent C(sp3)-H bonds.

Regiocontrol in traditional cycloaddition reactions between unsaturated carbon compounds is often challenging. The increasing focus in modern medicinal chemistry on benzocyclobutene (BCB) scaffolds indicates the need for alternative, more selective routes to diverse rigid carbocycles rich in C(sp3) character. Here, we report a palladium-catalyzed double C-H activation of two adjacent methylene units in carboxylic acids, enabled by bidentate amide-pyridone ligands, to achieve a regio-controllable synthesis of BCBs through a formal [2+2] cycloaddition involving σ bonds only (two C-H bonds and two aryl-halogen bonds). A wide range of cyclic and acyclic aliphatic acids, as well as dihaloheteroarenes, are compatible, generating diversely functionalized BCBs and hetero-BCBs present in drug molecules and bioactive natural products.

[Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II].

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 µmol/L) with or without Ang II (0.4 µmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.

Cholecystectomy and risk of liver disease: a systematic review and meta-analysis of 27 million individuals.

BACKGROUND: There is still a lack of knowledge on the association between cholecystectomy and liver disease. This study was conducted to summarize the available evidence on the association of cholecystectomy with liver disease and quantify the magnitude of the risk of liver disease after cholecystectomy. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched systematically from database inception to January 2023 to identify eligible studies that evaluated the association between cholecystectomy and the risk of liver disease. Meta-analysis was conducted to obtain a summary odds ratio (OR) and 95% confidence interval (CI) using a random-effects model. RESULTS: We identified 20 studies with a total of 27 320 709 individuals and 282 670 liver disease cases. Cholecystectomy was associated with an increased risk of liver disease (OR: 1.63, 95% CI: 1.34-1.98). In particular, cholecystectomy was found to be significantly associated with a 54% increased risk of nonalcoholic fatty liver disease (OR: 1.54, 95% CI: 1.18-2.01), a 173% increased risk of cirrhosis (OR: 2.73, 95% CI: 1.81-4.12), and a 46% increased risk of primary liver cancer (OR: 1.46, 95% CI: 1.18-1.82). CONCLUSIONS: There is an association between cholecystectomy and the risk of liver disease. Our results suggest that strict surgical indications should be implemented to reduce unnecessary cholecystectomy. Additionally, the routine assessment of liver disease is necessary for patients with a history of cholecystectomy. More prospective large-sample studies are required for better estimates of the risk.

Self-Assembled Plasmonic Nanojunctions Mediated by Host-Guest Interaction for Ultrasensitive Dual-Mode Detection of Cholesterol.

Herein, a fluorescence and surface-enhanced Raman spectroscopy dual-mode system was designed for cholesterol detection based on self-assembled plasmonic nanojunctions mediated by the competition of rhodamine 6G (R6G) and cholesterol with ß-cyclodextrin modified on gold nanoparticles (HS-ß-CD@Au). The fluorescence of R6G was quenched by HS-ß-CD@Au due to the fluorescence resonance energy transfer effect. When cholesterol was introduced as the competitive guest, R6G in the cavities of HS-ß-CD@Au was displaced to recover its fluorescence. Moreover, two of HS-ß-CD@Au can be linked by one cholesterol to form a more stable 2:1 complex, and then, plasmonic nanojunctions were generated, which resulted in the increasing SERS signal of R6G. In addition, fluorescence and SERS intensity of R6G increased linearly with the increase in the cholesterol concentrations with the limits of detection of 95 and 74 nM, respectively. Furthermore, the dual-mode strategy can realize the reliable and sensitive detection of cholesterol in the serum with good accuracy, and two sets of data can mutually validate each other, which demonstrated great application prospects in the surveillance of diseases related with cholesterol.

Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II / 生理学报

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.

HaASR2 from Haloxylon ammodendron confers drought and salt tolerance in plants.

Abscisic acid (ABA), stress, and ripening-induced proteins (ASR), which belong to the ABA/WDS domain superfamily, are involved in the plant response to abiotic stresses. Haloxylon ammodendron is a succulent xerohalophyte species that exhibits strong resistance to abiotic stress. In this study, we isolated HaASR2 from H. ammodendron and demonstrated its detailed molecular function for drought and salt stress tolerance. HaASR2 interacted with the HaNHX1 protein, and its expression was significantly up-regulated under osmotic stress. Overexpression of HaASR2 improved drought and salt tolerance by enhancing water use efficiency and photosynthetic capacity in Arabidopsis thaliana. Overexpression of HaASR2 maintained the homeostasis of reactive oxygen species (ROS) and decreased sensitivity to exogenous ABA and endogenous ABA levels by down-regulating ABA biosynthesis genes under drought stress. Furthermore, a transcriptomic comparison between wild-type and HaASR2 transgenic Arabidopsis plants indicated that HaASR2 significantly induced the expression of 896 genes in roots and 406 genes in shoots under osmotic stress. Gene ontology (GO) enrichment analysis showed that those DEGs were mainly involved in ROS scavenging, metal ion homeostasis, response to hormone stimulus, etc. The results demonstrated that HaASR2 from the desert shrub, H. ammodendron, plays a critical role in plant adaptation to drought and salt stress and could be a promising gene for the genetic improvement of crop abiotic stress tolerance.

The characteristics and correlations of vaginal flora in women with cervical lesions / 中华肿瘤杂志

Objective: To explore the characteristics and correlations of vaginal flora in women with cervical lesions. Methods: A total of 132 women, including 41 women diagnosed with normal cervical (NC), 39 patients with low-grade cervical intraepithelial neoplasia (CIN 1), 37 patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) and 15 patients with cervical squamous cell carcinoma (SCC), who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January 2018 to June 2018, were enrolled in this study according to the inclusive and exclusive criteria strictly. The vaginal flora was detected by 16S rDNA sequencing technology. Co-occurrence network analysis was used to investigate the Spearman correlations between different genera of bacteria. Results: The dominant bacteria in NC, CIN 1 and CIN 2/3 groups were Lactobacillus [constituent ratios 79.4% (1 869 598/2 354 098), 63.6% (1 536 466/2 415 100) and 58.3% (1 342 896/2 301 536), respectively], while Peptophilus [20.4% (246 072/1 205 154) ] was the dominant bacteria in SCC group. With the aggravation of cervical lesions, the diversity of vaginal flora gradually increased (Shannon index: F=6.39, P=0.001; Simpson index: F=3.95, P=0.012). During the cervical lesion progress, the ratio of Lactobacillus gradually decreased, the ratio of other anaerobes such as Peptophilus, Sneathia, Prevotella and etc. gradually increased, and the differential bacteria (LDA score >3.5) gradually evolved from Lactobacillus to other anaerobes. The top 10 relative abundance bacteria, spearman correlation coefficient>0.4 and P<0.05 were selected. Co-occurrence network analysis showed that Prevotella, Peptophilus, Porphyrinomonas, Anaerococcus, Sneathia, Atopobium, Gardnerella and Streptococcus were positively correlated in different stages of cervical lesions, while Lactobacillus was negatively correlated with the above anaerobes. It was found that the relationship between vaginal floras in CIN 1 group was the most complex and only Peptophilus was significantly negatively correlated with Lactobacillus in SCC group. Conclusions: The increased diversity and changed correlations between vaginal floras are closely related to cervical lesions. Peptophilus is of great significance in the diagnosis, prediction and early warning of cervical carcinogenesis.

Construction and validation of a personalized nomogram of ultrasound for pretreatment prediction of breast cancer patients sensitive to neoadjuvant chemotherapy.

OBJECTIVE: To construct a combined radiomics model based on pre-treatment ultrasound for predicting of advanced breast cancers sensitive to neoadjuvant chemotherapy (NAC). METHODS: A total of 288 eligible breast cancer patients who underwent NAC before surgery were enrolled in the retrospective study cohort. Radiomics features reflecting the phenotype of the pre-NAC tumors were extracted. With features selected using the least absolute shrinkage and selection operator (LASSO) regression, radiomics signature (Rad-score) was established based on the pre-NAC ultrasound. Then, radiomics nomogram of ultrasound (RU) was established on the basis of the best radiomic signature incorporating independent clinical features. The performance of RU was evaluated in terms of calibration curve, area under the curve (AUC), and decision curve analysis (DCA). RESULTS: Nine features were selected to construct the radiomics signature in the training cohort. Combined with independent clinical characteristics, the performance of RU for identifying Grade 4-5 patients was significantly superior than the clinical model and Rad-score alone (p < 0.05, as per the Delong test), which achieved an AUC of 0.863 (95% CI, 0.814-0.963) in the training group and 0.854 (95% CI, 0.776-0.931) in the validation group. DCA showed that this model satisfactory clinical utility, suggesting its robustness as a response predictor. CONCLUSION: This study demonstrated that RU has a potential role in predicting drug-sensitive breast cancers. ADVANCES IN KNOWLEDGE: Aiming at early detection of Grade 4-5 breast cancer patients, the radiomics nomogram based on ultrasound has been approved as a promising indicator with high clinical utility. It is the first application of ultrasound-based radiomics nomogram to distinguish drug-sensitive breast cancers.