Abstract Sojae semen germinatum (SSG) prepared from the germinating black soybean Glycine max L. Merr. is a traditional Chinese herbal medicine with heat-clearing, dampness-removing, and detoxifying properties. In the present study, we explored the effects and possible underlying mechanisms of petroleum ether extract (PEE), ethyl acetate extract (EAE), n-butanol extract (NBE) and aqueous fraction (AF) of SSG on the carbon tetrachloride (CCl4)-induced liver injury in mice, an animal model representing pathological features of “dampness-heat” syndrome from the perspective of Traditional Chinese Medicine. Results showed that the EAE and NBE of SSG significantly protected mice against the CCl4-induced increases of liver tissue index and serum transaminase levels, ameliorated the CCl4-induced liver morphological changes. Compared with CCl4 model controls, EAE and NBE of SSG decreased malondiadehyde (MDA) levels, enhanced glutathione (GSH) content and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver tissues, as well as reduced the number of apoptotic hepatocytes. Moreover, the CCl4-induced increase of pro-inflammatory cytokine levels in livers was markedly suppressed by pre-treatment with EAE of SSG. Data suggested that SSG extracts showed protective effect on the CCl4-induced liver injury via multiple pharmacological mechanisms including anti-oxidation, anti-inflammation and anti-apoptosis. EAE and NBE appeared to be superior to other fractions.

ABSTRACT Purpose: To investigate the role of cyanidin-3-O-glucoside (C3G) in renal ischemia/reperfusion (I/R) injury and the potential mechanisms. Methods: Mouse models were established by clamping the left renal vessels, and in vitro cellular models were established by hypoxic reoxygenation. Results: Renal dysfunction and tissue structural damage were significantly higher in the I/R group. After treatment with different concentrations of C3G, the levels of renal dysfunction and tissue structural damage decreased at different levels. And its protective effect was most pronounced at 200 mg/kg. The use of C3G reduced apoptosis as well as the expression of endoplasmic reticulum stress (ERS)-related proteins. Hypoxia/reoxygenation (H/R)-induced apoptosis and ERS are dependent on oxidative stress in vitro. In addition, both AG490 and C3G inhibited the activation of JAK/STAT pathway and attenuated oxidative stress, ischemia-induced apoptosis and ERS. Conclusions: The results demonstrated that C3G blocked renal apoptosis and ERS protein expression by preventing reactive oxygen species (ROS) production after I/R via the JAK/STAT pathway, suggesting that C3G may be a potential therapeutic agent for renal I/R injury.

This study aimed to evaluate in vitro the possible mechanisms underlying the estrogenic potential of benzalkonium chloride (BAC) as a disinfectant emerging contaminant. Effects of BAC at the environmentally-relevant concentrations on estrogen synthesis and estrogen receptor (ER) signaling were assessed using the H295R steroidogenesis assay and the MCF-7 proliferation assay, respectively. Results showed that exposure to BAC at concentrations of 1.0-1.5 mg/L for 48 h significantly increased estradiol production of H295R cells in a concentration-dependent manner. Transcription of steroidogenic genes 3β‐HSD2, 17β‐HSD1, 17β‐HSD4, and CYP19A were significantly enhanced by BAC. In ER-positive MCF-7 cells, exposure to 0.5-1.5 mg/L BAC for 48 h significantly promoted cell proliferation and increased the expressions of ERα and G-protein coupled estrogen receptor 1. Flow cytometry analysis showed that 0.5-1.5 mg/L BAC significantly decreased the percentage of cells in G0/G1 phase, increased the percentage in S phase, and BAC at concentrations of 1.0 and 1.5 mg/L increased the G2/M phase cells. Findings of the study suggested that BAC at environmentally-relevant concentrations might act as a xenoestrogen through its inhibitory effect on steroidogenesis and ER-mediated mechanism.

Abstract Adaptation of photoperiod-sensitive japonica rice varieties from long-day (LD) to short-day (SD) conditions is impeded by their extremely early flowering in response to photoperiod change, but the genetic factor underlying this is still elusive. We detected mutations in Hd1 in Zhenjing2400 through gene mapping and sequencing analysis. Genome resequencing of the varieties Zhenjing2400 and Jiahe218 identified single nucleotide polymorphisms (SNPs) in the other flowering-related genes Ehd1, SDG725, OsCOL15, DTH2, and DTH7. We constructed recombinant inbred lines (RILs) derived from a cross between Zhenjing2400 and Jiahe218, and selected homozygous lines with these six genes. We established that photoperiod insensitivity is caused by a defective Hd1 gene. In addition, the effect of Hd1 and Ehd1 on heading date was stronger than that of the other four genes. Measurements of agronomic traits and quality traits in homozygous lines demonstrated the superiority of the hd1 ehd1 genotype for eating quality and photoperiod-insensitive high yield. photoperiodsensitive sensitive longday long day LD (LD shortday short SD (SD change elusive Hd Zhenjing Zhenjing240 analysis Jiahe Jiahe21 SNPs (SNPs floweringrelated related Ehd SDG725 SDG OsCOL15 OsCOL DTH2 DTH DTH7 RILs (RILs addition hd ehd photoperiodinsensitive insensitive yield Zhenjing24 Jiahe2 SDG72 OsCOL1 Zhenjing2 SDG7

ABSTRACT Background: This study aimed to explore the prevalence and clinical risk factors in patients diagnosed with incidental prostate cancer (IPC) during certain surgeries (transurethral resection of the prostate [TURP], open prostatectomy [OP], and holmium laser enucleation of the prostate [HoLEP]) after clinically suspected benign prostatic hyperplasia (BPH). Materials and Methods: Literature search of the MEDILINE, Web of Science, Embase, and Cochrane Library databases was performed to identify eligible studies published before June 2021. Multivariate adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) of the prevalence and clinical risk factors of IPC were calculated using random or fixed-effect models. Results: Twenty-three studies were included in the meta-analysis. Amongst the 94.783 patients, IPC was detected in 24.715 (26.1%). Results showed that the chance of IPC detection (10%, 95% CI: 0.07-4.00; P<0.001; I2=97%) in patients treated with TURP is similar to that of patients treated with HoLEP (9%, 95% CI: 0.07-0.11; P<0.001; I2=81.4%). However, the pooled prevalence estimate of patients treated with OP was 11% (95% CI: −0.03-0.25; P=0.113; I2=99.1%) with no statistical significance. We observed increased incidence of IPC diagnosis after BPH surgery amongst patients with higher prostate-specific antigen (PSA) level (OR: 1.13, 95% CI: 1.04-1.23; P=0.004; I2=89%), whereas no effect of age (OR: 1.02, 95% CI: 0.97-1.06; P=0.48; I2=78.8%) and prostate volume (OR: 0.99, 95% CI: 0.96-1.03; P=0.686; I2=80.5%) were observed. Conclusions: The prevalence of IPC was similar amongst patients undergoing TURP, HoLEP, and OP for presumed BPH. Interestingly, increased PSA level was the only independent predictor of increasing risk of IPC after BPH surgery rather than age and prostate volume. Hence, future research should focus on predictors which accurately foretell the progression of prostate cancer to determine the optimal treatment for managing patients with IPC after BPH surgery.

Abstract Osteoarthritis (OA) is a degenerative joint disease associated with inflammation. Polygonatum sibiricum polysaccharide (PSP) is a major group of active components isolated from Polygonatum sibiricum with broad activities including anti-inflammatory effect. However, the role of PSP in OA is unclear. In the present study, we aimed to investigate the effects of PSP on IL-1β-induced inflammatory response in primary human OA chondrocytes. The results showed that PSP improved cell viability of chondrocytes in response to IL-1β induction. The increased levels of several inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IL-1β-induced chondrocytes were attenuated by PSP in a dose-dependent manner. The IL-1β-induced production of pro-inflammatory cytokines, TNF-α and IL-6, were mitigated by PSP in chondrocytes. Besides, PSP also suppressed the production of matrix metalloproteinases (MMPs), including MMP-1, MMP-3 and MMP-13 in IL-1β-stimulated chondrocytes. Furthermore, the IL-1β-induced activation of NF-κB signaling pathway in chondrocytes was also prevented by PSP. These findings suggested that PSP alleviated IL-1β-induced inflammatory response in chondrocytes via inhibiting NF-κB signaling pathway.

Abstract As one of classic Chinese kidney-tonifying herbal medicines, Taxillus chinensis (DC.) Danser is widely applied in Chinese folk medicine as herbal tea for nutraceutical purposes including nourishing kidney, strengthening muscle and bone to against weakness, etc. In the present study, we investigated the protective effect of aqueous extracts from Taxillus chinensis (AETCs) on the ovariectomy (OVX)-induced osteoporosis in rats. Results showed that AETC treatment at the dose of 12.0 g raw materials/kg for 12 weeks significantly enhanced the bone mineral densities of femur and tibia, improved the trabecular microarchitecture compared with OVX controls. The serum levels of osteogenic markers alkaline phosphatase and osteocalcin were increased, and the levels of bone resorption biomarkers tartrate-resistant acid phosphatase 5b and telopeptides of collagen type I were suppressed by AETCs. Moreover, 12.0 g raw materials/kg AETC treatment significantly reduced the OVX-induced up-regulation of cyclooxygenase (COX)-2 mRNA and protein expression in bone tissues. Data suggested that AETCs showed anti-osteoporotic effect in OVX rats, possibly via promoting bone formation and inhibiting bone absorption. The down-regulation of inflammatory COX-2 might be involved in the protection of AETCs against OVX –induced osteoporosis.

Abstract To study the caramel reactions of disaccharides with water, the type I maltose caramel products (MCPs) and sucrose caramel products (SCPs) at three reaction stages were yielded and their reaction rates, UV absorptions, flavor compounds, and antioxidant activities were also detected. It was found that the caramel reactions of sucrose were faster than those of maltose and their reaction rates quickly increased to a high level in the middle stage. UV absorption of SCP in the late stage at 305 nm was much stronger than those of MCPs. Both the MCP and SCP obtained at 180 °C and 4 min had the highest concentrations of 5-hydroxymethylfurfural and total flavor compounds. Moreover, the total flavor concentrations of SCPs were much larger than those of MCPs and the antioxidant effects of SCPs were also stronger. Thus, a preferred condition for both two disaccharide caramel reactions was suggested at 180 °C for 4 min and the sucrose caramels could give better flavors than maltose caramels.

Abstract Salted duck egg white was desalted and hydrolyzed to produce angiotensin I-converting enzyme (ACE) inhibitory peptides. Single factor test and response surface design were performed to determine the best hydrolysis conditions: enzyme dosage 11875.99 U/g, substrate concentration 33.04 g/L and hydrolysis time 4 h. The fraction V (MW < 1 kDa), which exhibited the strongest ACE inhibitory activity, was characterized by HPLC-ESI-MS/MS. Eighty-three peptides were identified, and among them Ile-Leu-Lys-Pro, Ile-Asn-Ser-Trp, Ile-Arg and His-Pro-Ala were synthesized for further research. Ile-Leu-Lys-Pro exhibited the highest ACE inhibitory activity (IC50: 0.355 mM). The molecular docking studies revealed that nine amino acids contributed to stabilize the docking complex. The ACE inhibition of Ile-Leu-Lys-Pro and Ile-Asn-Ser-Trp were mainly attributed to Ile in N-terminal. The residues Glu362 and Ala332 were the important binding sites in molecular docking. This research expands the understanding of ACE inhibitory peptides from duck egg white as well as highlights an opportunity for recycling an otherwise discarded byproduct.

Abstract Rock materials are often subjected to cyclic loads during construction. A full understanding of the deformation behavior of rock under cyclic loads is of great significance in engineering. In this study, by using the endochronic constitutive model proposed by Valanis, the reinforcement function form and constitutive parameters of the endochronic model are improved. An endochronic plasticity constitutive program for rock based on the finite element method is used to study the mechanical properties of rock under different cyclic loading conditions (of maximum loading stress, amplitude, and confining pressure), and through the use of red sandstone, marble, and basalt, experimental and simulation results are compared to verify the model. The results show that the theory can better simulate the hysteresis loop width and cumulative plastic strain of rock under cyclic loading and, under different loading conditions, the numerical simulation results are consistent with the actual rock experimental law. Therefore, the endochronic plasticity constitutive model in this study can be applied to investigate the influence of cyclic loading on the dynamic deformation behavior of rock.

Diabetes mellitus (DM) has a high prevalence in patients with pancreatic cancer (PaC), but the prognostic value of DM in PaC remains controversial. Alterations of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) contribute to multidrug resistance and intestinal metabolism in a variety of cancer types, which may be implicated in DM development. This study aimed to explore the potential prognostic value of P-gp and CYP3A4 in PaC patients in the context of DM through long-term follow-up. We retrospectively reviewed the medical records of patients with PaC admitted at The First People's Hospital of Changzhou, Jiangsu, China, from January 2011 to November 2019 and identified two cohorts of adult patients with PaC, including 24 with DM and 24 without DM (non-DM). The baseline clinical characteristics and outcomes were compared. Immunohistochemistry showed that protein expression of P-gp, but not CYP3A, in duodenum tissues was significantly upregulated in PaC patients with DM compared with those without DM. Kaplan-Meier analysis and log-rank test showed that the survival of patients with PaC and DM/high expression of P-gp was not significantly reduced compared with that of patients without DM/low expression of P-gp. These findings suggested that P-gp expression levels were different in the DM and non-DM groups of patients with PaC, but DM and duodenal P-gp levels were not associated with the long-term survival of patients with PaC. It appears that the presence of DM or P-gp expression levels may not serve as effective prognostic markers for PaC.

Abstract Background: Reports regarding the causative drugs of drug-induced cutaneous adverse reactions in China are indistinct, such that different regions have reported the spectrum of drugs differs substantially in different clinical conditions. Objective: To explore the causative drugs that led to cutaneous reactions. Methods: Adverse drug reaction reports from central China were collected and divided into cutaneous adverse reactions and severe cutaneous adverse reactions groups. Cases were reviewed retrospectively for causative drugs. Results: The male:female ratio was equal in both cutaneous adverse reactions and severe cutaneous adverse reactions. In cutaneous adverse reactions (n = 482), the highest incidence happened between 51 and 60 years of age and the top three causative drugs were antibiotics (48%), Chinese medicine (16%), and allopurinol (9%). In severe cutaneous adverse reactions (n = 126), the highest incidence happened between 41 and 50 years of age and the top three causative drugs were sedative-hypnotics and antiepileptics (39%), antibiotics (22%), and allopurinol (15%). Carbamazepine was the most frequently used single-drug (16/18) in sedative-hypnotics and antiepileptics. β-lactams were the most frequently used antibiotics that induced both cutaneous adverse reactions and severe cutaneous adverse reactions. Study limitations: The small sample size, retrospective design, collection of cutaneous adverse reactions and severe cutaneous adverse reactions at different time frames and locations, and exclusion of patients taking more than five medications are limitations of the study. Conclusions: Gender does not affect cutaneous adverse reactions and severe cutaneous adverse reactions. The top three drugs to induce cutaneous adverse reactions are antibiotics, Chinese medicine, and allopurinol, while those that triggered severe cutaneous adverse reactions are sedative-hypnotics and antiepileptics, antibiotics, and allopurinol. Carbamazepine is the most frequent single drug that induces severe cutaneous adverse reactions. β-lactams are the most frequently used antibiotics that induce both cutaneous adverse reactions and severe cutaneous adverse reactions.

Abstract: Background: Pityriasis rosea is a common papulosquamous disorder. However, its etiology and pathogenesis remain unclear. Objective: We investigate the types of inflammatory cells infiltrating the lesional skin of pityriasis rosea and demonstrate whether T-cell-mediated immunity is involved in the pathogenesis of this condition or not. Methods: The biopsies were taken from the lesional skin of 35 cases of patients diagnosed with pityriasis rosea. The specimens were prepared in paraffin sections, then submitted to routine immunohistochemistry procedures using monoclonal antibodies directed against CD3, CD4, CD8, CD20 and CD45RO and horseradish peroxidase-labeled goat anti-human antibodies. The positive sections were determined by the ratio and staining intensity of positive inflammatory cells. Results: The mean score of positive CD3, CD4, CD8, and CD45RO staining was respectively 3.74±3.88, 5.67±4.40, 2.94±3.42 and 7.68±4.33 in these pityriasis rosea patients (P<0.001). The percentage of positive staining was 54.29% (19/35), 69.7% (23/33), 40% (14/35) and 79.41% (27/34) (P<0.05). However, the staining of CD20 was negative in all samples. The mean score of CD3 staining in patients with time for remission ≤60 days (4.90±4.21) was higher than that in patients with time for remission >60 days (2.00±2.5) (P<0.05), whereas no statistical difference in the mean score of CD4, CD8 and CD45RO staining was observed. study liMitations: The sample size and the selected monoclonal antibody are limited, so the results reflect only part of the cellular immunity in the pathogenesis of pityriasis rosea. Conclusion: Our findings support a predominantly T-cell mediated immunity in the development of pityriasis rosea.

ABSTRACT The N absorption and assimilation is critical for the rice (Oryza sativa L.) yield increase when overdose N was applied in rice production. Three different rice genotypes, 'Quanliangyou 1' (Q1), 'Quanliangyou 681' (Q681) and 'Huanghuazhan' (HHZ), were selected to investígate the effects of elevated N input on the N partitioning, plant growth, grain quality and key genes involved in glutamate biosynthesis. Under increasing N inputs (0, 120, 180, 250 kg ha-1), N content in leaf, culm, seed and root were increased significantly. The increased N was preferentially deposited in leaf and culm. Tiller number, panicle number and length were also proved to be significantly promoted, but plant height and 1000-grain weight were nonsignificantly affected under elevated N input. Under high N input, seed protein content was elevated, while fatty acid and amylose content remained unchanged in comparison to low N input, but amylopectin content decreased. For the key genes in N assimilation, glutamine synthetase (OsGS1;1) could be induced by increasing N input (0 to 180 kg ha-1) but higher N input (250 kg ha-1) inhibit its expression, which showed similar response pattern with the glutamine synthetase activity. Although different rice genotypes showed similar response pattern to elevated N input, each genotype varied a lot in certain phenotypic indexes. And the response pattern of all these phenotypic characteristics to elevated N input was independent of rice genotype. These findings suggest that elevated N input could promote rice growth, reallocate N content in different tissues, and have negative impact on grain quality. This study provided physiological and molecular foundation for rice breeding and cultivation under high N input.

Abstract: Chuju, the flower of Chrysanthemum morifolim cv. Chuju, is a traditional medicine-food material used in China. Bioassay-guided chemical investigation on Chuju led the isolation of 16 flavonoids (1-16) characterized as quercetin (1), isorhamnetin 3-O-b-D-glucoside (2), eriodictyol (3), pyracanthoside (4), apigenin (5), apigetrin (6), acacetin (7), acacipetalin (8), luteolin (9), diosmetin (10), spinacetin (11), axillarin (12), bonanzin (13), cirsiliol (14), chrysosplenol D (15) and artemetin (16). Among them, compounds (11-16) were first reported from the Chrsanthemum species. Chuju flavonoids displayed strong antioxidant in DPPH (1, 1-diphenyl-2- picrylhydrazyl) radical scavenging assay, and high anti-inflammatory activity by inhibiting NO production in LPS-induced RAW 264.7 cells. These findings suggests that Chuju is an ideal source of natural flavonoids with significant antioxidant and anti-inflammatory effects, and is worthy of further development as health-promoting food or supplement.

Resumen: La flor de Chrysanthemum morifolim cv. Chuju, conocida popularmente como Chuju, se utiliza tradicionalmente como alimento y medicina en China. Un estudio químico biodirigido de un extracto de las flores condujo al aislamiento de 16 flavonoides, los cuales se caracterizaron como quercetina (1), isoramnetina 3-O-b-D-glucosido (2), eriodictiol (3), piracantosido (4), apigenina (5), apigetrina (6), acacetina (7), acacipetalina (8), luteolina (9), diosmetina (10), espinacetina (11), axilarina (12), bonanzina (13), cirsiliol (14), crisosplenol D (15) and artemetina (16). Los productos 11-16 se describen por primera vez en la especie. Los flavonoides de Chuju demostraron una notable actividad antioxidante en el ensayo de captación del radical 2,2- difenil-1-picrilhidrazilo (DPPH); asimismo presentaron un fuerte efecto antiinflamatorio in vitro, valorado a través de la inhibición de la producción de NO en macrófagos RAW 264.7 estimulados con LPS. Estos resultados indican que Chuju es una fuente importante de flavonoides antiinflamatorios y antioxidantes con un potencial importante para su desarrollo como agente nutracéutico.