Primordial follicle assembly in the mouse occurs during perinatal ages and largely determines the ovarian reserve that will be available to support the reproductive life span. The development of ...primordial follicles is controlled by a complex network of interactions between oocytes and ovarian somatic cells that remain poorly understood. In the present research, using single-cell RNA sequencing performed over a time series on murine ovaries, coupled with several bioinformatics analyses, the complete dynamic genetic programs of germ and granulosa cells from E16.5 to postnatal day (PD) 3 were reported. Along with confirming the previously reported expression of genes by germ cells and granulosa cells, our analyses identified 5 distinct cell clusters associated with germ cells and 6 with granulosa cells. Consequently, several new genes expressed at significant levels at each investigated stage were assigned. By building single-cell pseudotemporal trajectories, 3 states and 1 branch point of fate transition for the germ cells were revealed, as well as for the granulosa cells. Moreover, Gene Ontology (GO) term enrichment enabled identification of the biological process most represented in germ cells and granulosa cells or common to both cell types at each specific stage, and the interactions of germ cells and granulosa cells basing on known and novel pathway were presented. Finally, by using single-cell regulatory network inference and clustering (SCENIC) algorithm, we were able to establish a network of regulons that can be postulated as likely candidates for sustaining germ cell-specific transcription programs throughout the period of investigation. Above all, this study provides the whole transcriptome landscape of ovarian cells and unearths new insights during primordial follicle assembly in mice.
A high-throughput batch reactor system was designed for hydrogen production by catalytic gasification of bituminous coal in supercritical water. The experimental system was made up of six subsystems ...with the same parameters, which was designed with a maximum temperature and pressure of 750 °C and 30 MPa, respectively. The system ensures that a maximum of six series experiments are conducted at the same time, which promotes the efficiency of the experimental work. In this study, the experiments were conducted under different operational conditions: temperature of 600–750 °C, pressure of 23–25 MPa, feed concentration of 5–20 wt %, reaction time of 4–15 min, and K2CO3 addition rate of 0–200 wt %. The effects of operational conditions were examined. The results obtained show that the carbon gasification efficiency (CE) and gasification efficiency (GE) increased with decreasing feed concentration and increasing temperature, reaction time, and K2CO3 addition rate. The addition of K2CO3 promoted the gasification reactivity significantly. CE and GE in the catalytic case were about 1.7 and 2 times that in the non-catalytic case, respectively. Kinetic information on catalytic gasification of coal in supercritical water was experimentally investigated. The activation energy and pre-exponential factor obtained were 59.47 ± 4.87 kJ/mol and 43.89 ± 1.82 min–1, respectively.
The population history of Southeast (SE) China remains poorly understood due to the sparse sampling of present‐day populations and limited modeling with ancient genomic data. We report genome‐wide ...genotyping data from 207 present‐day Han Chinese and Hmong‐Mien (HM)‐speaking She people from Fujian and Taiwan Island, SE China. We coanalyzed 66 Early Neolithic to Iron Age ancient Fujian and Taiwan Island individuals obtained from previously published works to explore the genetic continuity and admixture based on patterns of genetic variations of the high‐resolution time transect. We found the genetic differentiation between northern and southern East Asians was defined by a north–south East Asian genetic cline and our studied southern East Asians were clustered in the southern end of this cline. The southeastern coastal modern East Asians are genetically similar to other southern indigenous groups as well as geographically close to Neolithic‐to‐Iron Age populations, but they also shared excess alleles with post‐Neolithic Yellow River ancients, which suggested a southward gene flow on the modern southern coastal gene pool. In addition, we identified one new HM genetic cline in East Asia with the coastal Fujian HM‐speaking She localizing at the intersection between HM and Han clines. She people show stronger genetic affinity with southern East Asian indigenous populations, with the main ancestry deriving from groups related to southeastern ancient indigenous rice farmers. The southeastern Han Chinese could be modeled with the primary ancestry deriving from the group related to the Yellow River Basin millet farmers and the remaining from groups related to rice farmers, which was consistent with the northern China origin of modern southeastern Han Chinese and in line with the historically and archaeologically attested southward migrations of Han people and their ancestors. Our estimated north–south admixture time ranges based on the decay of the linkage disequilibrium spanned from the Bronze Age to historic periods, suggesting the recent large‐scale population migrations and subsequent admixture participated in the formation of modern Han in SE Asia.
The population history of SE China remains poorly understood due to sparse sampling of present‐day populations and limited modeling with ancient genomic data. We report genome‐wide genotyping data from 207 present‐day Han Chinese and Hmong‐Mien‐speaking She people from Fujian and Taiwan, SE China. We coanalyzed 66 Early Neolithic to Iron Age ancient Fujian and Taiwan individuals obtained from previous works. We found the genetic differentiation between northern and southern East Asians was defined by a north–south East Asian genetic cline. The studied southeastern East Asians are genetically close to other southern Tai‐Kadai, Hmong‐Mien, Austronesian, and Austroasiatic speakers, as well as geographically close Neolithic‐to‐Iron Age ancient populations, but also share excess alleles with post‐Neolithic Yellow River ancients, suggesting the influence of southward gene flow from northern China on modern southern coastal gene pool. The She people derive the main ancestry from southern East Asian indigenous populations, while the southeastern Han Chinese could be modeled with the primary ancestry deriving from the group related to the Yellow River Basin millet farmers and the remaining from groups related to southeastern ancient indigenous rice farmers. Our estimated north–south admixture time ranges based on the decay of the linkage disequilibrium spanned from the Bronze Age to historic periods, suggesting the recent large‐scale population migrations and subsequent admixture participated in the formation of modern Han in SE Asia, which is in line with the historically and archaeologically attested southward migrations of Han people and their ancestors.
Auxiliary function-based summation inequalities are addressed in this technical note. By constructing appropriate auxiliary functions, several new summation inequalities are obtained. A novel ...sufficient criterion for asymptotic stability of discrete-time systems with time-varying delay is obtained in terms of linear matrix inequalities. The advantage of the proposed method is demonstrated by two classical examples from the literature.
Polygonatum kingianum has been widely regarded as a potential resource for anti-aging. In this study, we aimed to investigate the specific effect and action mechanism of saponins, the main active ...component of the plant, based on the current promising anti-aging targets. The results demonstrated that Polygonatum kingianum saponins (PKS) significantly delayed stress-induced and replicative cellular senescence. Model cells MRC-5 treated with PKS exhibited increased cell proliferation viability, reduced β-galactosidase activity, and improved cell cycle arrest. These positive trends were attributed to the senescence-associated secretory phenotype (SASP) down-regulation by PKS. The mRNA expression and factor secretion levels of some typical SASP factors, such as IL-6, IL-8, and CXCL-10, were significantly decreased under the effect of PKS, which effectively inhibited SASP-mediated senescence diffusion and improved the cellular microenvironment. Additionally, PKS was found to have a favorable effect on the healthy lifespan of model animals. Caenorhabditis elegans (C. elegans) treated with PKS showed increased lifespan, a significant reduction in lipofuscin accumulation, strengthened stress resistance ability, and enhanced antioxidant activity (SOD/CAT/MDA/ROS). Further mechanistic studies indicated that PKS can upregulate sir-2.1 in C. elegans and then affect the transcriptional activity of daf-16. Moreover, PKS exhibited autophagy-inducing effects, as evidenced by the up-regulated expression of autophagy-related genes (lgg-1 and bec-1) and an increased number of autophagosome monitored in worms treated with PKS. These findings suggest that PKS possesses the superiority of multiple pathways for anti-aging. As a promising anti-aging natural drug resource, PKS is worthy of further application and development.
•Polygonatum kingianum saponins (PKS) can significantly delay senescence in MRC-5 cells.•PKS is related to the down-regulation of senescence-associated secretory phenotype (SASP).•PKS could extend the healthy lifespan of Caenorhabditis elegans.•PKS anti-aging effect on C. elegans is correlated to sir-2.1 activation and autophagy induction.
Treg cells play a crucial role in immune tolerance, but mechanisms that induce Treg cells are poorly understood. We here have described eosinophils in lamina propria (LP) that displayed high aldehyde ...dehydrogenase (ALDH) activity, a rate-limiting step during all-trans retinoic acid (ATRA) synthesis, and expressed TGF-β1 mRNA and high levels of ATRA. Co-incubation assay confirmed that LP eosinophils induced the differentiation of naïve T cells into Treg cells. Differentiation promoted by LP eosinophils were inhibited by blocked either TGF-β1 or ATRA. Peripheral blood (PB) eosinophils did not produce ATRA and could not induce Treg differentiation. These data identifies LP eosinophils as effective inducers of Treg cell differentiation through a mechanism dependent on TGF-β1 and ATRA.
Alveolar echinococcosis (AE) is a fatal zoonosis caused by the larvae of Echinococcus multilocularis. However, current chemotherapy treatment options are based on benzimidazoles albendazole (ABZ) and ...mebendazole, which have limited efficacy. Therefore, novel drugs are necessary for the treatment of this disease. The anthelmintic effects of crocin were tested on E. multilocularis metacestodes, germinal cells and protoscoleces in vitro. Human foreskin fibroblasts (HFFs) and Reuber rat hepatoma (RH) cells were used to assess cytotoxicity. The in vivo efficacy of crocin was investigated in mice following secondary infection with E. multilocularis. Furthermore, collagen deposition and degradation in host tissues around the metacestodes were evaluated. In vitro, crocin had a median effective concentration of 11.36 muM against cultured E. multilocularis metacestodes, while it reduced germinal cell viability at a median inhibitory concentration of 10.05 muM. Crocin was less toxic to HFFs and RH mammalian cell lines than to metacestodes. Transmission electron microscopy revealed that crocin treatment resulted in structural damage in the germinal layer. In addition, 60.33 + or - 3.06% of protoscoleces were killed by treatment with 10 muM crocin for 7 days, indicating that crocin has a parasiticidal effect. In vivo, the metacestode weight was significantly reduced after the administration of crocin at 50 mg/kg and 100 mg/kg (55.1 and 68.1%, respectively). Metacestode pathology showed structural disruption of the germinal and laminated layers after crocin treatment. The crocin- and ABZ-treated groups presented significant increases in the levels of interleukin (IL)-2 and IL-4. Furthermore, crocin inhibited the expression of matrix metalloproteinases (MMPs) (MMP2 and MMP9) and promoted collagen deposition in the metacestode. Crocin was demonstrated to exert parasiticidal activity against E. multilocularis in vitro and in vivo, and can be developed as a novel drug for the treatment of AE.
Pathologic complete response (pCR) following preoperative systemic therapy is associated with improved outcomes after subsequent liver transplant/resection in hepatocellular carcinoma (HCC). However, ...the relationship between radiographic and histopathological response remains unclear.
We retrospectively examined patients with initially unresectable HCC who received tyrosine kinase inhibitor (TKI) plus anti-programmed death 1 (PD-1) therapy before undergoing liver resection between March 2019 and September 2021 across 7 hospitals in China. Radiographic response was evaluated using mRECIST. A pCR was defined as no viable tumor cells in resected samples.
We included 35 eligible patients, of whom 15 (42.9%) achieved pCR after systemic therapy. After a median follow-up of 13.2 months, tumors recurred in 8 non-pCR and 1 pCR patient. Before resection, there were 6 complete responses, 24 partial responses, 4 stable disease cases, and 1 progressive disease case, per mRECIST. Predicting pCR by radiographic response yielded an area under the receiver operating characteristic curve (AUC) of 0.727 (95% CI: 0.558-0.902), with an optimal cutoff value of 80% reduction in the enhanced area in MRI (called major radiographic response), which had a 66.7% sensitivity, 85.0% specificity, and a 77.1% diagnostic accuracy. When radiographic response was combined with α-fetoprotein response, the AUC was 0.926 (95% CI: 0.785-0.999); the optimal cutoff value was 0.446, which had a 91.7% sensitivity, 84.6%, specificity, and an 88.0% diagnostic accuracy.
In patients with unresectable HCC receiving combined TKI/anti-PD 1 therapy, major radiographic response alone or combined with α-fetoprotein response may predict pCR.
Background:
The outcomes of patients with postmenopausal breast cancer(PBC) can be improved through the early detection of intraocular metastases(IOMs). In this study, we investigated patients with ...PBC, and compared those with IOMs with those with non-intraocular metastases(NIOMs) in terms of blood lipid levels, and then differentiated the risk factors associated with IOMs.
Methods:
Student’s t-test and a chi-square test were used to discriminate between the IOMs and NIOMs groups. After establishing a Poisson regression model to analyze risk factors, we plotted receiver operating characteristic curves(ROC) to assess the quality of risk factors predicting IOMs.
Results:
The incidence of IOMs in PBC was 1.16%. There was no significant difference in terms of histopathology between the 2 groups. The levels of total cholesterol (TC), apolipoprotein A1(APOA1) and low-density lipoprotein(LDL) in IOMs were significantly lower than in NIOMs groups. Poisson regression suggested that low levels of APOA1 and LDL were risk factors for IOMs (P = 0.002 and P < 0.001, respectively). ROC curve analysis demonstrated that the cut-off values of APOA1 and LDL were 1.025 g/L and 2.415 mmol/L. The highest prediction accuracy for IOMs involved the combination of APOA1 and LDL (AUC = 0.881, P < 0.001).
Conclusion:
Our research demonstrates that low levels of APOA1 and LDL efficiently predict IOMs in PBC as risk factors, and the combination of APOA1 and LDL was more predictive than single factors.
Tsantan Sumtang, which consists of Choerospondias axillaris (Roxb.) Burtt et Hill, Myristica fragrans Houtt and Santalum album L, is a traditional and common prescription of Tibetan medicine. Tsantan ...Sumtang originates from Four Tantra with properties of nourishing heart and has been used as a folk medicine for cardiovascular diseases and heart failure in Qinghai, Tibet and Inner Mongolia. Our previous studies found that Tsantan Sumtang showed beneficial effects on right ventricular structure in hypoxia rats, while the underling mechanism remains unclear.
To elucidate the underlying mechanisms of Tsantan Sumtang attenuated right ventricular (RV) remodeling and fibrosis of chronic hypoxia-induced pulmonary arterial hypertension (HPAH) rats.
Fifty male Sprague Dawley (SD) rats (170 ± 20 g) were randomly divided into control group, hypoxia group, and hypoxia + Tsantan Sumtang groups (1.0 g· kg−1·day−1, 1.25 g· kg−1·day−1, 1.5 g ·kg−1·day−1). Rats in the hypoxia group and hypoxia + Tsantan Sumtang groups were maintained in a hypobaric chamber by adjusting the inner pressure and oxygen content to simulate an altitude of 4500 m for 28 days. The mean pulmonary arterial pressure (mPAP), right ventricle hypertrophy index (RVHI), the ratio of RV weight to tibia length (TL) (RV/TL), heart rate (HR) and RV systolic pressure (RVSP) was determined. Histomorphological assay of RV structure was evaluated by hematoxylin and eosin (HE) staining. RV tissue fibrosis was assessed by collagen proportion area (CPA), collagen I, collagen III and hydroxyproline content. CPA was obtained by picro-sirius red staining (PSR). The expression of collagen I and collagen III were detected by immunohistochemistry and western blotting. The hydroxyproline content was detected by alkaline hydrolysis. In addition, the level of angiotensin II (AngII) and angiotensin 1-7 (Ang1-7) in RV tissue was tested by enzyme-linked immune sorbent assay (ELISA). Protein expression of angiotensin-converting enzyme (ACE), AngII, AngII type 1 receptor (AT1R), angiotensin-converting enzyme 2 (ACE2), Mas receptor (Mas) were determined by immunohistochemistry and western blotting. mRNA level of ACE, AT1R, ACE2, Mas were tested by qPCR. The chemical profile of Tsantan Sumtang was revealed by UHPLC-Q-Exactive hybrid quadrupole-orbitrap mass analysis.
Our results showed that RVHI, RV/TL and RVSP were significantly increased in HPAH rat. Furthermore, levels of collagen I, collagen III and hydroxyproline were up-regulated in RV tissue under hypoxia. We found that RV hypertrophy and fibrosis were associated with increased expression of ACE, AngII, AT1R as well as decreased expression of ACE2, Ang1-7 and Mas. RV remodeling and fibrosis were attenuated after Tsantan Sumtang administration by up-regulating ACE2 and Mas level as well as down-regulating ACE, AngII and AT1R levels in RV tissue. 35 constituents in Tsantan Sumtang were identified.
Tsantan Sumtang attenuated RV remodeling and fibrosis in rat exposed to chronic hypoxia. The pharmacological effect of Tsantan Sumtang was based on equilibrating ACE-AngII-AT1R and ACE2-Ang1-7-Mas axis of RV tissue in HPAH rat.
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