Search

The tumor microenvironment (TME) enhances regulatory T (T

13 páginas.- 5 figuras.- 1 tabla.- referencias., Palaeoclimate legacies have been reported to influence microbial communities and carbon (C) stocks even after thousands of years. However, the direct and indirect influences of climate legacies on microbial C processes remain poorly understood and thus limit our capacity to predict how climate legacies regulate C cycling. Here, we conducted microbial, soil and vegetation surveys along a continental latitudinal transect of 4200 km covering a wide range of forest biomes. With these data, we evaluated the potential capacity of climate legacies to predict direct and indirect variations in microbial metabolic quotient (MMQ) across and within three main forest biomes: tropical, subtropical and temperate, Shengen Liu and Qingkui Wang were supported by the National Natural Science Foundation of China (grant numbers 32101491, 32171752 and 31830015), fellowships of the China Postdoctoral Science Foundation (2022 T150375 and 2021 M701968) and Strategic Priority Research Program of the Chinese Academy of Sciences (grant number XDB15010301). G.Z. acknowledges sup-port from the Humbodlt Research Foundation. M.D-B. acknowl-edges support from the Spanish Ministry of Science and Innovation for the I+D+i project PID2020-115813RA-I00 funded by MCIN/AEI/10.13039/501100011033. M.D-B. is also supported by a pro-ject of the Fondo Europeo de Desarrollo Regional (FEDER) and the Consejería de Transformación Económica, Industria, Conocimiento y Universidades of the Junta de Andalucía (FEDER Andalucía 2014-2020 Objetivo temático “01 - Refuerzo de la investigación, el de-sarrollo tecnológico y la innovación”) associated with the research project P20_00879. (ANDABIOMA)

Pomegranate flowers (PFs) were reported to possess various biological activities such as antidiabetic, anti-inflammatory and hepatoprotective activities, and using to treat diabetes. Although chemical constituents and pharmacological activities of PFs have been studied, unfortunately, there was no report on the pharmacokinetic profile of PFs in vivo. In this study, a selective high-performance liquid chromatography triple quadrupole tandem mass spectrometry (HPLC–QQQ–MS/MS) method was developed and validated for simultaneous quantification of four compounds (corilagin, ellagic acid, gallic acid and brevifolincarboxylic acid) in rat plasma after oral administration of PFs. The good linearity concentration ranges for the four analytes were from 2.5 to 3000 ng/mL with coefficient value R2 > 0.99 in calibration curves. The intra- and inter-day accuracy of the four analytes was in the range of 85.33–102.50%, with relative standard deviation (RSD) of

Functional elucidation of bovine Y-chromosome genes requires available genome editing technologies. Meanwhile, it has yet to be proven whether the bovine Sry gene is the main or single factor involved in the development of the male phenotype in bovine. Here, we efficiently knocked out four Y-linked genes (Sry, ZFY, DDX3Y, and EIF2S3Y) in bovine fetal fibroblasts (BFFs) with transcription activator-like effector nucleases (TALENs) individually. Furthermore, we used TALEN-mediated gene knockin at the Sry gene and generated a sex-reversal bovine by somatic cell nuclear transfer (SCNT). The resulting bovine had only one ovary and was sterile. We demonstrate, for the first time, that the Sry gene is an important sex-determining gene in bovine. Our method lays a solid foundation for detecting the biology of the bovine Y chromosome, as it may provide an alternative biological model system for the study of mammalian sex determination, and new methods for the practical application in agricultural, especially for sex predetermination.

The metabolic profiles of Tanreqing injection, which is a traditional Chinese medicine recommended for complementary administration to treat a novel coronavirus, have remained unclear, which inhibit the understanding of the effective chemical compounds of Tanreqing injection. In this study, a sensitive high-performance liquid chromatography quadrupole time-of-flight mass spectrometry method was used to identify the compounds and metabolites in various biosamples, including plasma, bile, liver, lung, kidney, urine, and feces, following the intravenous administration of Tanreqing injection in rats. A total of 89 compounds were characterized in the biosamples of Tanreqing injection-treated rats including 25 precursor constituents and 64 metabolites. Nine flavonoid compounds, twelve phenolic acids, and four iridoid glycosides were identified in the rats. Their metabolites were mainly produced by glucuronidation, deglucuronidation, glycosylation, deglycosylation, methylation, demethylation, N-heterocyclisation, sulphation, dehydroxylation, decarboxylation, dehydration, hydroxylation, and corresponding recombination reactions. This study was the first to comprehensively investigate the metabolic profile of Tanreqing injection and provides a scientific basis to further elucidate the pharmacodynamic material basis and therapeutic mechanism of Tanreqing injection.

Introduction The treatment of intestinal perforation caused by the SBC enters the small intestine in elderly patients is a challenge for urologists. The report is to share our experience of conservative treatment after a 90-year-old male with the suprapubic bladder catheter enters the small intestine. Presentation of case Because of the device was obstructed, a 90-year-old male went to our hospital with his family and requested to replace the SBC. When the fistula tube was replaced, it entered the intestine through the intestinal injury site instead of entering the bladder. During the hospitalization, the patient was given supportive treatments and the SBC was dynamically monitored daily and it was intermittently withdrawn out during this period. After the drainage volume was less than 10 mL for three consecutive days and the intestinal fistula was healing gradually, the catheter was taken out. Discussion According to our experience, the common complications in the process include failure to pull out the SBC, abnormal position of the SBC, and poor drainage of the SBC. However, the drainage tube placing into the small intestine through the original hole of the suprapubic bladder fistula during the replacement process is quite rare. When elderly patients have traumatic small bowel perforation, the diagnosis and treatment of intestinal perforation in elderly patients was particularly important. Conclusion The conservative treatment of intestinal perforation is suitable for elderly patients who are unsuitable or unwilling to undergo a surgical operation. Of course, it should be in accordance with the patient's condition to make the right choice of treatment.

Positive and negative effects coexist in applying nitrification inhibitors (NIs) in China, making it difficult to accurately evaluate the risks and benefits brought by applying NIs. Thus, this study comprehensively investigated the benefits and risks for the environment and crops when applying three commonly used NIs: 3,4-dimethypyrazole phosphate (DMPP), dicyandiamide (DCD), and 2-chloro-6-trichloromethyl pyridine (nitrapyrin) in China. A meta-analysis including 617 observations from 172 studies in China was conducted in this study. DMPP, DCD, and nitrapyrin averagely reduced nitrous (N2O) emissions by 60.1%, 30.4%, and 36.1%, nitrate (NO3−) leaching by 49.5%, 51.9%, and 49.4%, respectively. Methane (CH4) and carbon dioxide (CO2) emissions were also inhibited by NIs. However, the application of DMPP, DCD, and nitrapyrin aggravated ammonia (NH3) volatilization by 43.2%, 27.4%, and 28.5%, respectively, and ammonium (NH4+) leaching by an average of 28.2%, 80.1%, and 30.9%, respectively. NIs increased crop yields and the magnitudes of the effects were in the following order: nitrapyrin (8.6–12%) > DCD (6.9–10.3%) > DMPP (5.8–8%). Furthermore, plant NO3− content was reduced by NIs and crop growth characteristics and qualities (e.g., plant height and sugar content) all exhibited positive responses to NI application. NI application provided benefits by decreasing N2O, CH4, and CO2 emissions and NO3−-N leaching and by enhancing crop yields and quality. The risks of NI application were caused by increasing NH3 volatilization and NH4+-N leaching. Considering all the environmental and crop factors together, the benefits in applying NIs were greater than the risks.

The temperature sensitivity (Q₁₀) of soil organic carbon (SOC) decomposition is an important parameter for those seeking accurate projections of SOC dynamics and its feedback on climate change in terrestrial ecosystems. However, how Q₁₀ responds to N deposition across environmental gradients and the underlying mechanism remain largely unresolved. We conducted a novel incubation experiment with periodically varying temperature based on the of soil origin sites to elucidate the responses of Q₁₀ to N addition across China. Our results demonstrated that N addition effects (NAEs) on Q₁₀ were negatively related to latitude and were strongly site dependent. Bioclimatic, edaphic, and microbial variables together explained 50.1% of the total variation in NAEs on Q₁₀, but bioclimate (16.0%) had the greater explanation than edaphic (11.8%) and microbial properties (6.3%). The response of soil exchangeable Ca²⁺ to N addition was a predictive power for NAEs on Q₁₀, contributing 7.2% relative importance in regulating this variation. Furthermore, arbuscular mycorrhizal fungi indicated by Glomeromycota were the best microbial predictor and contributed 10.9% relative importance in the variation regulating NAEs on Q₁₀. Overall, our results suggest that increasing N addition will increase the sensitivity of SOC decomposition to global warming and highlight the importance of bioclimate, exchangeable Ca²⁺, and arbuscular mycorrhizal fungi in predicting the response of Q₁₀ to N deposition in natural terrestrial ecosystems. The biogeographic variation in response of Q₁₀ to N deposition should be considered in carbon‐climate models to decrease the prediction uncertainties of SOC dynamics and its feedback to global warming.

The chemotherapeutic drug Doxorubicin is the most commonly prescribed in the world. However, its clinical wide application is limited due to harmful side effects like cardiotoxicity. The cardiotoxic mechanism of DOX is not fully clear, however, it is considered as a potential etiological factor to the generation of ROS and Iron complexes, impairment, Ca

In the modern multishaft gas turbine engines, orifice is an important throttling element, and the discharge coefficient of rotating orifices may vary considerably depending on the operating conditions, the geometry, and surrounding environment. The influences of the rotating number and the pressure ratio on the rotating orifices' flow characteristics are investigated in this study. Besides, the effects of confined space, wall inclination angle (α), and the angle between the axis of orifice and the disk wall normal (β) are also analyzed statistically. It is found that the rotating number has a significant effect on the discharge coefficient. As the rotating number increases from 0 to 0.6, the discharge coefficient reduces by about 47.88%. When rotating number is 0.74 and pressure ratio is 1.10, the discharge coefficient can be improved by 16.88% with α changes from 90 deg to 180 deg. The parameter, β, affects discharge coefficient slightly in rotating condition. However, the maximum discharge coefficient is achieved with β = 0 deg in the static condition. The results also show that a confined space weakens the effect of rotation and changes the air flow direction in the inlet chamber, which also has a positive impact on the discharge coefficient. In the current research, it is found that there is a significant difference between the traditional empirical formulas used in the literature and the fitting result. By modifying the incidence angle and taking account of the influence of the angle of inclination, the maximum error was reduced from 56.79% to 3.16%.

RNase III DROSHA is upregulated in multiple cancers and contributes to tumor progression by hitherto unclear mechanisms. Here, we demonstrate that DROSHA interacts with β-Catenin to transactivate STC1 in an RNA cleavage-independent manner, contributing to breast cancer stem-like cell (BCSC) properties. DROSHA mRNA stability is enhanced by N(6)-methyladenosine (m(6)A) modification which is activated by AURKA in BCSCs. AURKA stabilizes METTL14 by inhibiting its ubiquitylation and degradation to promote DROSHA mRNA methylation. Moreover, binding of AURKA to DROSHA transcript further strengthens the binding of the m(6)A reader IGF2BP2 to stabilize m(6)A-modified DROSHA. In addition, wild-type DROSHA, but not an m(6)A methylation-deficient mutant, enhances BCSC stemness maintenance, while inhibition of DROSHA m(6)A modification attenuates BCSC traits. Our study unveils the AURKA-induced oncogenic m(6)A modification as a key regulator of DROSHA in breast cancer and identifies a novel DROSHA transcriptional function in promoting the BCSC phenotype.

Purpose: To investigate the feasibility of retroperitoneal laparoscopic ipsilateral nephrectomy of a benign nonfunctional kidney after percutaneous nephrostomy, and to compare this method with open...

Urolithiasis has become more prevalent throughout China.Knowing stone composition helps identify their possible underlying etiology of urolithiasis, provide appropriate individualized treatment and prevent stone recurrence.To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone localization and geographical region on stone composition.We used Fourier transform infrared spectroscopy to analyse urinary stones from consecutive patients at 46 hospitals in seven geographic areas of China between June 1, 2010 and May 31, 2015.Chi-squared tests and logistic regression analyses were performed to determine associations between stone composition and sex, age, body mass index (BMI), stone location, and geographic region.The most common stone components were calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), brushite (1.7%), and cystine (0.9%). CaOx and urate occurred more frequently in males, whereas carbapatite and struvite were more common in females (p

Background: Currently, there are relatively few studies on the effects of changes in estrogen and androgen levels on prostatic MVD.This article aimed to study the changes of prostatic MVD in SD rats after castration under the effect of estrogen/androgen at different concentrations.Methods: Male Sprague-Dawley(SD) rats aged 3-4 months were randomly divided into the control group, castration group, and different concentrations of estrogen/ androgen treatment after castration. Dihydrotestosterone(DHT) and estradiol(E) were administered daily by subcutaneous injection for one month. All the rats were sacrificed by cervical dislocation after one month, and the serum DHT and E concentrations of the rats in each group were measured by ELISA assay. Prostate tissues specimens were immunohistochemically stained with monoclonal antibodies against CD-34 and factor VIII for the MVD.Results: Compared with the control group, the MVD decreased significantly in the castration group (PConclusions: Androgens carried an important role in the regulation of prostatic MVD in SD rats, and the decrease of DHT concentration can induce a decrease in prostatic MVD. In contrast, prostatic MVD can be increased with the increase of DHT concentration. In addition, prostatic MVD can be increased gradually with the increase of estrogen concentration.

Background Currently, there are relatively few studies on the effects of changes in oestrogen and androgen levels on prostatic microvessel density (MVD). This article aimed to study the changes in prostatic MVD in Sprague-Dawley (SD) rats after castration under the effect of oestrogen/androgen at different concentrations. Methods Male SD rats aged 3–4 months were randomly divided into a control group, a castration group, and groups with different concentrations of oestrogen/androgen treatment after castration. Dihydrotestosterone (DHT) and oestradiol (E) were administered daily by subcutaneous injection for one month. All the rats were killed by cervical dislocation after one month, and the serum DHT and E concentrations of the rats in each group were measured by ELISA. Prostate tissue specimens were immunohistochemically stained with monoclonal antibodies against CD34 and factor VIII for MVD. Results Compared with the control group, the MVD decreased significantly in the castration group (P P P Conclusions Androgens play an important role in the regulation of prostatic MVD in SD rats, and a decrease in DHT concentration can induce a decrease in prostatic MVD. In contrast, prostatic MVD can be increased with increasing DHT concentration. In addition, prostatic MVD can be increased gradually with increasing oestrogen concentration.

Atherosclerotic cardiovascular disease resulting from dysregulated lipid metabolism is the leading cause of morbidity and mortality worldwide. Apolipoprotein E (ApoE) plays a critical role in cholesterol metabolism. Knockouts in lipid-metabolizing proteins including ApoE in multiple model organisms such as mice and rats exhibiting elevated levels of cholesterol have been widely used for dissecting the pathology of atherosclerosis, but few of these animal models exhibit advanced atherosclerotic plaques leading to ischemia-induced clinical symptoms, limiting their use for translational studies. Here we report hypercholesterolemia and severe atherosclerosis characterized by stenosis and occlusion of arteries, together with clinical manifestations of stroke and gangrene, in ApoE knockout dogs generated by CRISPR/Cas9 and cloned by somatic cell nuclear transfer technologies. Importantly, the hypercholesterolemia and atherosclerotic complications in F0 mutants are recapitulated in their offspring. As the ApoE-associated atherosclerosis and clinical manifestations in mutant dogs are more similar to that in human patients compared with those in other animal models, these mutant dogs will be invaluable in developing and evaluating new therapies, including endovascular procedures, against atherosclerosis and related disorders.

Background Inputs of above- and belowground litter into forest soils are changing at an unprecedented rate due to continuing human disturbances and climate change. Microorganisms drive the soil carbon (C) cycle, but the roles of above- and belowground litter in regulating the soil microbial community have not been evaluated at a global scale. Methods Here, we conducted a meta-analysis based on 68 aboveground litter removal and root exclusion studies across forest ecosystems to quantify the roles of above- and belowground litter on soil microbial community and compare their relative importance. Results Aboveground litter removal significantly declined soil microbial biomass by 4.9% but root exclusion inhibited it stronger, up to 11.7%. Moreover, the aboveground litter removal significantly raised fungi by 10.1% without altering bacteria, leading to a 46.7% increase in the fungi-to-bacteria (F/B) ratio. Differently, root exclusion significantly decreased the fungi by 26.2% but increased the bacteria by 5.7%, causing a 13.3% decrease in the F/B ratio. Specifically, root exclusion significantly inhibited arbuscular mycorrhizal fungi, ectomycorrhizal fungi, and actinomycetes by 22.9%, 43.8%, and 7.9%, respectively. The negative effects of aboveground litter removal on microbial biomass increased with mean annual temperature and precipitation, whereas that of root exclusion on microbial biomass did not change with climatic factors but amplified with treatment duration. More importantly, greater effects of root exclusion on microbial biomass than aboveground litter removal were consistent across diverse forest biomes (expect boreal forests) and durations. Conclusions These data provide a global evidence that root litter inputs exert a larger control on microbial biomass than aboveground litter inputs in forest ecosystems. Our study also highlights that changes in above- and belowground litter inputs could alter soil C stability differently by shifting the microbial community structure in the opposite direction. These findings are useful for predicting microbe-mediated C processes in response to changes in forest management or climate.

Dysregulation of the nuclear export machinery mediated by chromosomal maintenance 1 (CRM1, also known as exportin-1), is closely associated with various human disorders, such as breast cancer. Previously, we identified sulforaphene and its synthetic analogues as covalent inhibitors of CRM1. Herein, we describe the discovery and biological evaluation of another sulforaphene synthetic analogue, LFS-31, as a potential CRM1 inhibitor. In addition, we investigated the reversible binding mechanism of LFS-31 with CRM1 through molecular simulations coupled with bio-layer interferometry (BLI) and found relatively high binding affinity (KD = 43.1 ± 35.3 nM) between the LFS-31 and CRM1 groups. We found that LFS-31 exhibited a stronger growth suppression of triple-negative breast cancer (TNBC) cells than non-TNBC cells, and had minimal effect on normal breast cells. Pharmacological treatment of TNBC cells with LFS-31 at nanomolar concentrations led to the nuclear retention of IkBα resulting in strong suppression of NF-κB transcriptional activity and attenuated cell growth and proliferation, which collectively contributed to the antitumor responses. To the best of our knowledge, this is the first study to demonstrate the use of a sulforaphene analogue as a potent CRM1 inhibitor that targets the NF-κB signaling pathway for the targeted therapy of TNBC.

Background: Serum prostate-specific antigen (PSA) is a primary metric for diagnosis and prognosis of prostate cancer (PCa). Exposure to heavy metals, such as lead, cadmium, mercury, and zinc can impact PSA levels in PCa patients. However, it is unclear whether this effect also occurs in men without PCa, which may lead to the overdiagnosis of PCa.Method: Data on a total of 5,089 American men who had never been diagnosed with PCa were obtained from the National Health and Nutrition Examination Survey performed from 2003–2010. The relationship between serum PSA levels (dependent variable) and concentrations of lead (μmol/L), cadmium (nmol/L), and mercury (μmol/L) were investigated with dietary zinc intake being used as a potential modifier or covariate in a weighted linear regression model and a generalized additive model. A series of bootstrapping analyses were performed to evaluate sensitivity and specificity using these models. Results: Regression analyses suggested that, in general, lead, cadmium, or mercury did not show an association with PSA levels, which was consistent with the results of the bootstrapping analyses. However, in a subgroup of participants with a high level of dietary zinc intake (≥14.12 mg/day), a significant positive association between cadmium and serum PSA was identified (1.06, 95% CI, P=0.0268, P for interaction=0.0249).Conclusions: With high-level zinc intake, serum PSA levels may rise in PCa-free men as the exposure to cadmium increases, leading to a potential risk of an overdiagnosis of PCa and unnecessary treatment. Therefore, environmental variables should be factored in the current diagnostic model for PCa that is solely based on PSA measurements. Different criteria for PSA screening are necessary based on geographical variables. Further investigations are needed to uncover the biological and biochemical relationship between zinc, cadmium, and serum PSA levels to more precisely diagnose PCa.

Yin-Chen-Hao Tang (YCHT), consisting of Artemisia annua L., Gardenia jasminoides Ellis, and Rheum Palmatum L., has been used to relieve liver diseases in China for thousands of years. Several protective mechanisms of YCHT on liver injury have been investigated based on metabolomics, but the effects of YCHT on the alterations in the gut microbiota are still unclear. In this study, an integrated approach based on 16S rRNA gene sequencing combined with high-performance liquid chromatography-mass spectrometry (HPLC-MS) metabolic profiling was performed to assess the effects of YCHT on liver injury induced by carbon tetrachloride (CCl4) through the regulation of the relative abundances of gut microbiota and their relationships with biomarker candidates. A total of twelve significantly altered bacterial genera and nine metabolites were identified, which returned to normal levels after YCHT treatment. The relative abundances of the identified microbiota, including significantly elevated amounts of p_Firmicutes, c_Clostridia, o_Clostridiales, f_Ruminococcaceae, g_[Eubacterium]_coprostanoligenes_group, s_uncultured_bacterium_f_Lachnospiraceae and remarkedly increased amounts of p_Bacteroidetes, c_Bacteroidia, o_Bacteroidales, f_Bacteroidaceae, g_Bacteroides and s_uncultured_bacterium_g_Bacteroides, were found in model rats compared with controls. Potential biomarkers, including lower levels of LysoPC (16:1(9Z)/0:0), LysoPC (20:3(5Z,8Z,11Z)), LysoPC (17:0), LysoPC (20:1(11Z)) and 3-hydroxybutyric acid and higher amounts of ornithine, L-kynurenine, hippuric acid and taurocholic acid are involved in several custom metabolic pathways, such as arginine and proline metabolism, tryptophan metabolism, glycerophospholipid metabolism and primary bile acid biosynthesis. Interestingly, there was a strong correlation between the perturbed gut microbiota in genera c_Clostridia and o_Clostridiales and the altered plasma metabolite 3-hydroxybutyric acid. This finding means that the hepatoprotective effects of YCHT may be due to the regulation of the production of the functional metabolite 3-hydroxybutyric acid through changes in the proportions of c_Clostridia and o_Clostridiales. These results showed that the hepatoprotective effects of YCHT not only focused on custom metabolic pathways but also depended on the changes in the gut microbiota in liver injury. These findings suggest that the 16S rRNA gene sequencing and LC-MS based metabolomics approach can be applied to comprehensively evaluate the effects of traditional Chinese medicines (TCMs).

Priming effect (PE) of soil organic carbon (SOC) decomposition induced by exogenous organic C is an important ecological process in regulating the soil C cycle. The objective of this study was to evaluate how the PE varied among different ecosystems at the global scale and explore factors that drive the direction and magnitude of the PE. Using 2048 experimental comparisons compiled from 94 incubation studies with stable (13C) or radioactive (14C) carbon isotopic techniques, we performed a meta-analysis on the effect of exogenous organic C input on native SOC decomposition (i.e., PE) across multiple terrestrial ecosystems. In particular, the linear mixed-effect model was used to examine the relationship between the PE and potential influencing factors. The addition of exogenous organic C significantly enhanced native SOC decomposition by 47.5% (i.e., positive PE), with the highest value in cropland soils (60.9%) and the lowest value in forest soils (26.2%). The intensity of the PE decreased with increasing SOC content, soil total nitrogen content, soil C/N, incubation duration, and incubation temperature, but increased with increasing exogenous organic C addition rate and soil pH. Soil PE was not affected by the complexity of exogenous organic C. Our results indicate that positive PE is a widespread phenomenon in terrestrial ecosystems, and that the magnitude is closely related to soil properties and experimental conditions. These findings may be useful for understanding soil C priming and the effect on soil C balance under climate change scenarios.

Prostate cancer (PCa) is the most common malignant tumor for men. But the mechanism is unclear. EIF3C was shown to be overexpressed in PCa tissues and cell lines. EIF3C overexpression was correlated to age and tumor stage in PCa patients and indicated poor survival. The proliferation, migration, and invasiveness of PC3 cells were all inhibited after EIF3C knockdown. Additionally, the phosphorylation level of PI3K and Akt was downregulated while total NF-κB and Myc decreased after EIF3C knockdown. But the expression of IκB increased reversely. Therefore, EIF3C at least partially regulates the activity of PI3K/Akt/NF-κB signaling pathway in PC3 cells.

A carbon supported carbon nitride is reported here as a catalyst for the direct conversion of acetylene and 1,2-dichloroethane (EDC) to vinyl chloride monomer (VCM). We demonstrate that increasing ...

In this study, Yin-Chen-Hao-Tang prepared by two decoction methods, namely, combined decoction (modern decoction method) and separated decoction (traditional decoction method), was analyzed by high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. The acquired datasets containing sample codes, tR -m/z pairs and ion intensities were processed with multivariate statistical analyses, such as principal component analysis and an orthogonal partial least squared discriminant analysis model, to globally compare the chemical differences between the different decoction samples. Then, the chemical differences between the combined and separated decoctions were screened out by S-plots generated from the orthogonal partial least squared discriminant analysis model and compared with chemical information from an established in-house library. The six components that contributed the most to the chemical differences were identified as chlorogenic acid, caffeic acid, geniposide, genipin, scopoletin, and 3,5-dicaffeoylquinic acid. The concentrations of genipin and caffeic acid from the separated decoction were higher than those from the combined decoction, indicating that the separated decoction may present a stronger hepatoprotective effect. However, the results still require further investigation through pharmacological and clinical studies. Our findings not only establish a strategy to evaluate chemical consistency of Yin-Chen-Hao-Tang but also provide the scientific basis for using traditional separated decoction method.

Ethnopharmacological revelvance CGA consisting of Cordyceps sinensis mycelia polysaccharide, gypenosides and amygdalin, was demonstrated to be the effective components formula in Fuzheng Huayu (FZHY) capsule, a traditional Chinese medicine approved by China food and drug administration for treatment of liver fibrosis and to inhibit transforming growth factor-β1 (TGF-β1) signaling, previously. Aim of the study To evaluate the effects of CGA on hepatic apoptosis in liver fibrosis induced by carbon tetrachloride (CCl4). Materials and methods The hepatic injury and histology was detected by serum biomarker assay and hematoxylin-eosin staining. The hepatic collagen was illustrated by Sirius red staining and hydroxyproline (Hyp) concentration. The hepatic stellate cells (HSCs) activation and hepatic apoptosis was visualized by immunohistochemical analysis of α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase-mediated dUPT nick-end labeling (TUNEL) assay respectively. The protein expression of collagen type I (Col-I), α-SMA, TGF-β1, Fas, tumor necrosis factor receptor 1 (TNF-R1), cleaved-caspase-8, cleaved-caspase-10, cleaved-caspase-9, cleaved-caspase-3, mitochondrial Bcl-2, Bcl-2 associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak), cytochrome C and cytoplasmic cytochrome C was detected by western-blot. Results CGA or FZHY ameliorated liver histological changes, decreasing serum alanine aminotransferase, aspartate aminotransferase, hepatic Hyp, TUNEL positive-stained area, and down-regulated the protein expression of α-SMA, TGF-β1, Col-I, Fas, TNF-R1, cleaved-caspase-8, cleaved-caspase-10, cleaved-caspase-9, and cleaved-caspase-3, mitochondrial Bax, Bak, and cytoplasmic cytochrome C, while restored the expression of mitochondrial Bcl-2 and cytochrome C. Conclusion CGA formula ameliorates liver fibrosis induced by CCl4, which is correlated to its inhibition on hepatic apoptosis.

Alcohol liver disease is a major public health problem associated with lifestyle. Our recent study demonstrated that the roots of Panax notoginseng saponins (PNS) exert hepatoprotective effects against alcohol consumption. Considering that the leaves of Panax notoginseng saponins (LPNS) have similar chemical ingredients with PNS, increased attention should be given to the hepatoprotective effects of LPNS. In this study, a metabonomic approach based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) was developed to evaluate the hepatoprotective effect of LPNS on alcoholic fatty liver and elucidate the interaction mechanisms. Results showed that the ethanol-induced metabolic perturbations were restored after treatment with LPNS. Furthermore, 12 potential biomarkers (11 upregulated and 1 downregulated) were identified by V-plot and orthogonal partial least square discriminant analysis. Changes in the levels of these metabolites indicated that glycerophospholipid and fatty acid metabolism were disturbed in alcoholic fatty liver mouse. Our findings demonstrated that the UHPLC–QTOF/MS-based metabonomic method may provide a useful means for exploring biomarkers involved in alcoholic fatty liver and elucidating the therapeutic effects of LPNS. This work also showed that the metabonomic approach is a powerful and promising tool for the evaluation of the efficacy of traditional Chinese medicine and elucidation of related mechanisms.

Objectives The present study aimed to investigate the influence of urine on re-epithelialization in canine prostatic urethra after prostatectomy and explore possible causes. Method We established two groups of prostatic canine models. The first group contained urine that canines underwent the surgery by two-micron laser resection of the prostate-tangerine technique (TmLRP-TT), and no transurethral catheter was required. The second group was without urine that canines accepted the surgery by TmLRP-TT add ureter skin ostomy urine bypass. Histopathology of re-epithelialization of repair in trauma in canine prostatic urethra was observed by hematoxylin and eosin (HE) staining, and immunochemistry was used to determine the expression of transforming growth factor-β1 (TGF-β1). Human prostate epithelial line (BPH-1) cells were cultured with or without urine and the abilities of proliferation and migration were tested by CCK-8 and transwell assays, respectively. Results The histology displayed that there was distinct proliferation of prostatic cell under the wound after 3 days, re-epithelialization began after 9 days, and finished after 28 days at urine group. The TGF-β1 like-IR in prostatic epithelium cells and fibroblast cells under the wound at urine group were strikingly increased as compared with the cells at no urine group after 3, 9, and 11 days, respectively (p

Background: Our previous studies revealed that the downregulation of Suppressor of cytokine signaling 6 (SOCS6) was correlated with malignant progression of human prostate cancer (PCa). Aims: In the current study, we aimed to investigate the tumor suppressive roles of SOCS6 and the underlying mechanisms in PCa. Methods: SOCS6 expression in PCa and non-cancerous prostate tissues was compared by immunohistochemistry. Statistical associations of SOCS6 expression with various clinicopathological features and patients prognosis were evaluated. In addition, we investigated SOCS6’s functions by overexpressing it in vitro (cell apoptosis, migration and invasion assays) and in vivo (tumor formation, angiogenesis and apoptosis). Moreover, SOCS6-regulated genes were identified by nextgeneration RNA-sequencing analysis, followed by pathway enrichment analysis and in vitro experimental validation. Results: SOCS6 downregulation was significantly associated with advanced clinical stage (P=0.029) and positive lymph node metastasis (P=0.013) in PCa patients. We also identified SOCS6 as an independent prognostic factor for disease-free survival in PCa patients (P=0.045). Moreover, overexpression of SOCS6 inhibited PCa cell invasion, migration, tumor xenografts growth and angiogenesis, but induced PCa cell apoptosis (P values Conclusion: These findings suggest that the reduced expression of SOCS6 may be predictive of unfavorable prognosis in PCa. Thus, SOCS6 may serve as a tumor suppressor and a novel therapeutic target for this cancer.

Litter decomposition plays important roles in maintaining ecosystem function and controlling carbon (C) and nutrient cycle in terrestrial ecosystems. Thus, understanding its fundamental controlling factors is of great value to improve the accuracy of biologically driven global carbon (C) cycle of prediction models. In this study, we conducted a field decomposition experiment with 205 tree species litters and quantified the relative importance of litter nutrients, C-related and physical traits in controlling litter decomposition in different plant functional groups. The results showed that across all species, litter nutrients (65.1%) explained more variation in litter decomposition than physical (17.5%) and C-related traits (17.4%). Litter nutrients had lower explanation for deciduous species (47.0%) than for evergreen species (77.9%), while C-related and physical traits had higher explanation for deciduous litters (20.5% and 32.5%) than for evergreen species (13.5% and 8.6%), suggesting that the importance of these three categorized litter traits in controlling litter decomposability was plant functional type dependent. Nitrogen, tannins and water saturation capacity were the best predictors of litter decomposition among nutrients, C-related and physical traits, respectively, irrespective of plant functional types. In sum, our findings highlight the differences in the roles of initial litter nutrients, C-related and physical traits in regulating litter decomposition and suggest that litter trait-decomposition relationships vary substantially between deciduous and evergreen species, necessitating their explicit consideration in Earth’s C cycle models to improve the accuracy of predicting litter decomposition.

Background: To clarify the expression of histological inflammation and major inflammatory factors in prostate of castrated rats induced by different concentrations estrogen/ androgen. Methods: Male Sprague-Dawley (SD) rats aged 3-4 months were randomly divided into the blank group (sham operation group, bilateral testicular specimens were retained), and the castration group (surgical removal of bilateral testes) and different concentrations of estrogen/androgen treatment after castration. Dihydrotestosterone (DHT) and estradiol (E) were administered daily by subcutaneous injection for one month, and the rats in each group were sacrificed by neck-broken method after one month. Obtained prostate specimens by surgery, and performed routine paraffin embedding and sectioning of prostate tissue. Observed the changes of prostate tissue structure and prostate inflammation under light microscope after Hematoxylin-eosin (HE) staining. Immunohistochemical method was used to detect the expression of TGF-β1, IL-6 and IL-8 in the rats prostate tissues. Results: After castration, when the exogenous E concentration was constant, the exogenous DHT(0-0.15mg/kg) concentration of SD rats in each group increased gradually, and the anatomical position score of inflammatory cell infiltration in each group of rats gradually increased. Further, even if the DHT concentration increased again after the exogenous DHT concentration reached at 0.5mg/kg, the score did not increase but decreased insteadly. From the area of tissues involved in inflammatory cell infiltration and the density of typical inflammatory cells, the inflammation score of each group of rats increased gradually with the increase of DHT concentration. When the exogenous DHT concentration was constant, from the anatomical location and the area of tissues involved in inflammatory cell infiltration in each group of SD rats, the inflammation score of each group of rats increased gradually with the increase of exogenous E concentration. The results of the immunohistochemical reaction showed that the positive rates of TGF-β1, IL-6 and IL-8 in SD rats after castration were higher than those in the blank group, and the positive rate of TGF-β1 was statistically significant compared with the blank group (PConclusions: Sex hormone levels are involved in the regulation of prostate inflammation in SD rats. Different levels of estrogen and androgen have different levels of inflammatory response to prostate inflammation and the expression of TGF-β1, IL-6, IL-8 in castrated SD rats, and the positive expression of TGF-β1, IL-6, IL-8 can reflect the inflammation of prostate tissue in SD rats to a certain extent. In addition, there may be an inflection point between the ratio of estrogen/ androgen and prostate inflammation. After crossing this inflection point, the inflammation of the prostate did not further deepen even if the concentration of exogenous androgens increased again. Of course, it needs to be confirmed by more systematic and comprehensive experiments in vivo and vitro.

Rhizosphere processes play a critical role in soil organic carbon (SOC) cycling that is primarily regulated by temperature. Understanding the response of rhizospheric SOC decomposition to global warming, which is called temperature sensitivity (Q10), is pivotal for predicting the feedback of SOC cycling to global warming. However, the rhizosphere effects (REs) on Q10 and their underlying mechanisms in forest ecosystems remain unclear. Here, the REs on Q10 for Cunninghamia lanceolata and three understory ferns (e.g., Woodwardia japonica, Parathelypteris glanduligera and Microlepia marginata) in a subtropical forest were explored using a novel incubation procedure with periodically changing temperatures based on the mean annual temperature. Our results showed that the positive REs on Q10 were observed for all plant species, which ranged from 33% to 88%, and P. glanduligera exhibited higher REs on Q10 than C. lanceolata. The positive REs on Q10 were associated with the rhizospheric nitrogen (N) availability and microbial properties. The REs on N component (i.e., the REs on total N, NH4+ and NO3− along the first PCA axis), which is the most important driver, had a positive direct effect on the REs on Q10. Furthermore, the rhizospheric microbial biomass and the REs on microbial residues were also positively related to the REs on Q10. Overall, these findings highlight that plant-covered soils have high risks of C emissions under planetary warming, underscore the importance of root-soil interactions for accurately predicting SOC dynamics and reveal that rhizospheric nutrients and microbial properties drive the feedback of the root-associated SOC cycle to global warming.

Climate warming potentially changes the flowering seasons of terrestrial plants, and thus species interaction, with consequently substantial impacts on ecosystem structure and function. However, the general response patterns of flowering seasons to warming and the underlying mechanisms remain poorly understood. Here, a meta-analysis of data from 26 experimental studies examining 168 species was conducted to quantify the responses of the flowering seasons of terrestrial plants to experimental warming. The results showed that experimental warming prolonged the flowering season by 2.08% across all species included in this study. In addition, flowering season responses were dependent on plant functional types, with a significant extension in herbaceous species (+2.18%) but no change in woody species. The warming impacts on the flowering season of wind-pollinated (-4.53%) and insect-pollinated species (+4.21%) were opposite. Among herbaceous species, the flowering seasons of forb (+4.47%) and specifically legume species (+15.06%) were positive, whereas grass species (-4.53%) showed negative responses to experimental warming. Moreover, experimental warming effects on the flowering season showed quadratic relationships with the latitude and the mean annual temperature but did not change with the mean annual precipitation. The responses of the flowering season to experimental warming also differed in terms of the warming magnitude. These diverse findings indicate the need for additional experimental warming experiments, especially for underrepresented plant functional groups, to better understand the mechanistic relationships between phenology and temperature under future climate warming scenarios.

Globally rising soil microbial respiration (Rm) is a key process controlling the soil-to-atmosphere CO2 flux, yet its spatial variation and underlying mechanism at different scales is still poorly understood. A novel experiment based on the annual mean temperature of soil origin sites along a 4,200 km north–south transect of China forests revealed a hump-shaped relationship between Rm and latitude with a latitudinal threshold of 32.5°N. Microbial variables were more important in shaping Rm’ spatial variation at the continental scale than at the regional scales, but soil physicochemical property had comparably unique importance at different scales. Labile organic C was the most important factor in regulating the Rm’s variation at the continent and in the latitude > 32.5°N region, but fungi biomass was the most important factor in the latitude < 32.5°N region. Overall, our findings suggest different controlling factors of Rm’s variations on either side of the latitudinal threshold.

The recent emerged SARS-CoV-2 may first transmit to intermediate animal host from bats before the spread to humans. The receptor recognition of ACE2 protein by SARS-CoVs or bat-originated coronaviruses is one of the most important determinant factors for the cross-species transmission and human-to-human transmission. To explore the hypothesis of possible intermediate animal host, we employed molecular dynamics simulation and free energy calculation to examine the binding of bat coronavirus with ACE2 proteins of 47 representing animal species collected from public databases. Our results suggest that intermediate animal host may exist for the zoonotic transmission of SARS-CoV-2. Furthermore, we found that tree shrew and ferret may be two putative intermediate hosts for the zoonotic spread of SARS-CoV-2. Collectively, the continuous surveillance of pneumonia in human and suspicious animal hosts are crucial to control the zoonotic transmission events caused by SARS-CoV-2.

Regulatory T cells (Tregs) are required to control immune responses and maintain homeostasis but are a significant barrier to anti-tumor immunity1. Conversely, Treg instability, characterized by loss of the master transcription factor Foxp3 and acquisition of pro-inflammatory properties2, can promote autoimmunity and/or facilitate more effective tumor immunity3,4. A comprehensive understanding of the pathways that regulate Foxp3 could lead to more effective Treg therapies for autoimmune disease and cancer. Despite improved functional genetic tools that now allow for systematic interrogation, dissection of the gene regulatory programs that modulate Foxp3 expression has not yet been reported. In this study, we developed a CRISPR-based pooled screening platform for phenotypes in primary mouse Tregs and applied this technology to perform a targeted loss-of-function screen of ∼490 nuclear factors to identify gene regulatory programs that promote or disrupt Foxp3 expression. We discovered several novel modulators including ubiquitin-specific peptidase 22 (Usp22), Ataxin 7 like 3 (Atxn7l3) and ring finger protein 20 (Rnf20). Members of the deubiquitination module of the SAGA chromatin modifying complex, Usp22 and Atxn7l3, were discovered to be positive regulators that stabilized Foxp3 expression; whereas the screen suggested Rnf20, an E3 ubiquitin ligase, is a negative regulator of Foxp3. Treg-specific ablation of Usp22 in mice reduced Foxp3 protein and created defects in their suppressive function that led to spontaneous autoimmunity but protected against tumor growth in multiple cancer models. Foxp3 destabilization in Usp22-deficient Tregs could be rescued by ablation of Rnf20, revealing a reciprocal ubiquitin switch in Tregs. These results reveal novel modulators of Foxp3 and demonstrate a screening method that can be broadly applied to discover new targets for Treg immunotherapies for cancer and autoimmune disease.

Qushi Huayu Fang (QHF) is a clinic-empirical prescription for treating non-alcoholic fatty liver disease (NAFLD) in China, which is composed of five herbs. However, the bioactive constituents responsible for the efficacy of QHF remain unclear. Thus, a high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method was established and adopted to identify the constituents of QHF, and profile its metabolism in vivo and in vitro. Among the 66 constituents in QHF, only 14 compounds of six structural types were absorbed, and 34 metabolites were generated through eight metabolic pathways. A total of 20 metabolites were first reported, including four organic acids, one iridoid, two flavones, five naphthols, three anthraquinones, and five stilbenes. Glucuronidation and sulfation were the main metabolic pathways, and the intestinal metabolism played an important role in the biotransformation of QHF. Many compounds, especially those detected in the liver, the target organ of QHF, were reported to display the anti-NAFLD activity. This is the first study to explore the constituents of QHF and its metabolism in vivo and in vitro, thus realizing the first step to clarify the chemical basis of QHF qualitatively, and laying the foundation for further research on the anti-NAFLD mechanism of QHF.

Increasing fire risk and atmospheric nitrogen (N) deposition have the potential to alter plant community structure and composition, with consequent impacts on biodiversity and ecosystem functioning. This study was conducted to examine short‐term responses of understory plant community to burning and N addition in a coniferous‐broadleaved mixed forest of the subtropical‐temperate transition zone in Central China. The experiment used a pair‐nested design, with four treatments (control, burning, N addition, and burning plus N addition) and five replicates. Species richness, cover, and density of woody and herbaceous plants were monitored for 3 years after a low‐severity fire in the spring of 2014. Burning, but not N addition, significantly stimulated the cover (+15.2%, absolute change) and density (+62.8%) of woody species as well as herb richness (+1.2 species/m2, absolute change), cover (+25.5%, absolute change), and density (+602.4%) across the seven sampling dates from June 2014 to October 2016. Light availability, soil temperature, and prefire community composition could be primarily responsible for the understory community recovery after the low‐severity fire. The observations suggest that light availability and soil temperature are more important than nutrients in structuring understory plant community in the mixed forest of the subtropical‐temperate transition zone in Central China. Legacy woody and herb species dominated the understory vegetation over the 3 years after fire, indicating strong resistance and resilience of forest understory plant community and biodiversity to abrupt environmental perturbation.

The genetic modification of cattle has many agricultural and biomedical applications. However, random integration often results in the unstable expression of transgenes and unpredictable phenotypes. Targeting genes to the “safe locus” and stably expressing foreign genes at a high level are desirable methods for overcoming these hurdles. The Rosa26 locus has been widely used to produce genetically modified animals in some species expressing transgenes at high and consistent levels. For the first time, we identified a bovine orthologue of the mouse Rosa26 locus through a genomic sequence homology analysis. According to 5′ rapid-amplification of cDNA ends (5′RACE), 3′ rapid-amplification of cDNA ends (3′RACE), reverse transcription PCR (RT-PCR) and quantitative PCR (Q-PCR) experiments, this locus encodes a long noncoding RNA (lncRNA) comprising two exons that is expressed ubiquitously and stably in different tissues. The bovine Rosa26 (bRosa26) locus appears to be highly amenable to transcription activator-like effector nucleases (TALENs)-mediated knock-in, and ubiquitous expression of enhanced green fluorescent protein (EGFP) inserted in the bRosa26 locus was observed in various stages, including cells, embryos, fetus and cattle. Finally, we created a valuable master bRosa26-EGFP fetal fibroblast cell line in which any gene of interest can be efficiently introduced and stably expressed using recombinase-mediated cassette exchange (RMCE). The new tools described here will be useful for a variety of studies using cattle.

Recent large high-quality trials have questioned the clinical effectiveness of medical expulsive therapy using tamsulosin for ureteral stones.To evaluate the efficacy and safety of tamsulosin for distal ureteral stones compared with placebo.We conducted a double-blind, placebo-controlled study of 3296 patients with distal ureteral stones, across 30 centers, to evaluate the efficacy and safety of tamsulosin.Participants were randomly assigned (1:1) into tamsulosin (0.4mg) or placebo groups for 4 wk.The primary end point of analysis was the overall stone expulsion rate, defined as stone expulsion, confirmed by negative findings on computed tomography, over a 28-d surveillance period. Secondary end points included time to stone expulsion, use of analgesics, and incidence of adverse events.Among 3450 patients randomized between September 1, 2011, and August 31, 2013, 3296 (96%) were included in the primary analysis. Tamsulosin benefits from a higher stone expulsion rate than the placebo (86% vs 79%; p0.001) for distal ureteral stones. Subgroup analysis identified a specific benefit of tamsulosin for the treatment of large distal ureteral stones (5mm). Considering the secondary end points, tamsulosin-treated patients reported a shorter time to expulsion (p0.001), required lower use of analgesics compared with placebo (p0.001), and significantly relieved renal colic (p0.001). No differences in the incidence of adverse events were identified between the two groups.Our data suggest that tamsulosin use benefits distal ureteral stones in facilitating stone passage and relieving renal colic. Subgroup analyses find that tamsulosin provides a superior expulsion rate for stones5mm, but no effect for stones ≤5mm.In this report, we looked at the efficacy and safety of tamsulosin for the treatment of distal ureteral stones. We find that tamsulosin significantly facilitates the passage of distal ureteral stones and relieves renal colic.