[Effect and mechanism of Jiedu Huoxue Decoction in regulating YAP/ACSL4 pathway to inhibit ferroptosis in treatment of acute kidney injury].

Jiedu Huoxue Decoction(JDHX), first recorded in the Correction on Errors in Medical Works by WANG Qing-ren, is an effective formula screened out from ancient formulas by the traditional Chinese medicine(TCM) master ZHANG Qi to treat acute kidney injury(AKI) caused by heat, toxicity, stasis, and stagnation. This paper elucidated the therapeutic effect of JDHX on AKI and probed into the potential mechanism from ferroptosis. Thirty-two male C57BL/6 mice were randomized into four groups(n=8): normal, model, and low-and high-dose JDHX. Since the clinical treatment of AKI depends on supportive or alternative therapies and there is no specific drug, this study did not include a positive drug group. The low dose of JDHX corresponded to half of clinically equivalent dose, while the high dose corresponded to the clinically equivalent dose. Mice were administrated with JDHX by gavage daily for 7 consecutive days, while those in the normal group and the model group were administered with the corresponding volume of distilled water. On day 5 of drug administration, mice in other groups except the normal group were injected intraperitoneally with cisplatin solution at a dose of 20 mg·kg~(-1) to induce AKI, and the normal group was injected with saline. All of the mice were sacrificed 72 h after modeling, blood and kidney samples were collected for subsequent analysis. The levels of serum creatine(Scr) and blood urea nitrogen(BUN) were measured by the commercial kits. The expression level of kidney injury molecule 1(KIM-1) in the serum was measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin(HE) staining, periodic acid-Schiff(PAS) staining, and Prussian blue staining were employed to observe the pathological changes, glycogen deposition, and iron deposition, respectively, in the renal tissue. In addition, the levels of glutathione(GSH), superoxide dismutase(SOD), and catalase(CAT) in the renal tissue were examined by biochemical colorimetry. Western blot was performed to determine the protein levels of acyl-CoA synthetase long chain family member 4(ACSL4), lysophosphatidylcholine acyltransferase 3(LPCAT3), and Yes-associated protein(YAP, a key molecule in the Hippo pathway) in the renal tissue. Immunohistochemistry was then employed to detect the location and expression of YAP in the renal tissue. Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR) was performed to measure the mRNA levels of ACSL4 and glutathione peroxidase 4(GPX4). Compared with the normal group, the model group showed elevated serum levels of Scr, BUN, and KIM-1. In the AKI model group, the tubular epithelial cells underwent atrophy and necrotic detachment, disappearance of brush border, and some tubules became protein tubules or experienced vacuole-like degeneration. In addition, this group presented widening of the interstitium or even edema, increased renal tubule injury score, and obvious glycogen and iron deposition in parts of the renal tissue. Moreover, the model group had lower GSH, SOD, and CAT levels, higher ASCL4 and LPCAT3 levels, and lower GPX4 expression and higher YAP expression than the normal group. Compared with the model group, high dose of JDHX effectively protected renal function, lowered the levels of Scr, BUN and KIM-1, alleviated renal pathological injury, reduced glycogen and iron deposition, and elevated the GSH, SOD, and CAT levels in the renal tissue. Furthermore, JDHX down-regulated the protein levels of ACSL4, LPCAT3, and YAP and up-regulated the level of GPX4, compared with the model group. In conclusion, JDHX can protect mice from cisplatin-induced AKI by inhibiting ferroptosis via regulating the YAP/ACSL4 signaling pathway.

Phosphate deficiency responsive TaSPX3 is involved in the regulation of shoot phosphorus in Arabidopsis plants.

SPX (SYG/PHO81/XPR1) domain genes have been reported to play vital roles in the Phosphorus (Pi) signaling network in Arabidopsis thaliana and rice. However, the functions of SPX proteins in wheat remain largely unknown. In this study, the full-length cDNA sequence of the TaSPX3 gene was cloned from the common wheat variety Zhengmai9023. The expression of TaSPX3 was up-regulated in eight different genotypes of wheat under low phosphorus (LP) stress, indicating that TaSPX3 responds to Pi limitation in multiple wheat genotypes. The transcription level of TaSPX3 was also detected in the absence of seven different elements, showing certain specificity for Pi deficiency in wheat. Over expressing TaSPX3 in Arabidopsis can alleviate Pi deficiency symptoms at the seedling stage and promote the growth of plant, and advance the flowering period at the adult stage. The expression of 7 genes associated with the Pi starvation signal pathways was analyzed using qRT-PCR. The results showed that TaSPX3, along with AtSPX1, AtRNS1, AtIPS1, AtPAP2, AtPAP17 and AtAT4, were all induced by Pi deficiency. This study reveals that the TaSPX3 gene in wheat is involved in the response to phosphorus stress and may affect shoot phosphorus levels through AT4 or PAPs-related pathways. Overall, our study provides new insights into the regulation of plant response under LP conditions and the molecular mechanism underlying the role of the wheat SPX gene in coping with LP stress.

The co-phytotoxicity of two Asteraceae invasive plants Solidago canadensis L. and Bidens pilosa L. with different invasion degrees.

The phytotoxicity of invasive plants (IPS) has been identified as one of the main factors influencing their invasion success. The invasion of IPS can occur to varying degrees in the habitats. Two IPS can invade one habitat. This study aimed to evaluate the mono- and co-phytotoxicity of two Asteraceae IPS Solidago canadensis L. and Bidens pilosa L. with different invasion degrees (including light invasion (relative abundance <50%) and heavy invasion (relative abundance ≥50%)) on the horticultural Asteraceae species Lactuca sativa L., through a hydroponic experiment conducted on 9 cm Petri dishes. Leaf extracts of the two IPS can cause significant mono- and co-phytotoxicity. The mono- and co-phytotoxicity of the two IPS were concentration-dependent. The mono-phytotoxicity of S. canadensis was significantly increased with increasing invasion degree, but the opposite was true for the mono-phytotoxicity of B. pilosa. Leaf extracts of B. pilosa with light invasion caused stronger phytotoxicity than those of S. canadensis with light invasion. There may be an antagonistic effect for the co-phytotoxicity caused by mixed leaf extracts of the two IPS compared with those of either S. canadensis or B. pilosa. The phytotoxicity of the two IPS on the growth performance of neighboring plants may play a more important role in their mono-invasion than in their co-invasion. The phytotoxicity appeared to affect the growth performance of S. canadensis individuals more significantly when the invasion was heavy, while the growth performance of B. pilosa individuals seemed to be more influenced by phytotoxicity when the invasion was light. Consequently, the concentration of leaf extracts of IPS, the invasion degree of IPS, the species identity of IPS, and the species number of IPS modulated the mono- and co-phytotoxicity of the two IPS.

The effect of epigallocatechin gallate on laying performance, egg quality, immune status, antioxidant capacity, and hepatic metabolome of laying ducks reared in high temperature condition.

Epigallocatechin gallate (EGCG) is a main component in green tea extract, which possesses multiple bioactivities. The present research studied the effects of EGCG on the laying performance, egg quality, immune status, antioxidant capacity, and hepatic metabolome of Linwu laying ducks reared under high temperature. A total of 180 42-w-old healthy Linwu laying ducks were allocated into control or EGCG-treated groups. Each treatment had 6 replicates with 15 ducks in each replicate. Diets for the two groups were basal diets supplemented with 0 or 300 mg/kg EGCG, respectively. All ducks were raised in the high temperature condition (35 ± 2 °C for 6 h from 10:00 to 16:00, and 28 ± 2 °C for the other 18 h from 16:00 to 10:00 the next day) for 21 days. Results showed that EGCG increased the egg production rate (p = 0.014) and enhanced the immunocompetence by improving serum levels of immunoglobulin A (p = 0.008) and immunoglobulin G (p = 0.006). EGCG also fortified the antioxidant capacity by activating superoxide dismutase (p = 0.012), catalase (p = 0.009), and glutathione peroxidase (p = 0.021), and increasing the level of heat-shock protein 70 (p = 0.003) in laying ducks' liver. At the same time, hepatic metabolomics result suggested that EGCG increased the concentration of several key metabolites, such as spermidine (p = 0.031), tetramethylenediamine (p = 0.009), hyoscyamine (p = 0.026), ß-nicotinamide adenine dinucleotide phosphate (p = 0.038), and pantothenic acid (p = 0.010), which were involved in the metabolic pathways of glutathione metabolism, arginine and proline metabolism, ß-alanine metabolism, and tropane, piperidine, and pyridine alkaloid biosynthesis. In conclusion, 300 mg/kg dietary EGCG showed protection effects on the laying ducks reared in high temperature by improving the immune and antioxidant capacities, which contributed to the increase of laying performance of ducks. The potential mechanism could be that EGCG modulate the synthesis of key metabolites and associated metabolic pathways.

Clerodendranthus spicatus inhibits epithelial-mesenchymal transition of renal tubular cells through the NF-κB/Snail signalling pathway in hyperuricaemia nephropathy.

CONTEXT: Clerodendranthus spicatus Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to treat hyperuricaemic nephropathy (HN). OBJECTIVE: To investigate the molecular mechanism of action of CS in HN treatment using in vivo and in vitro experiments. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into control, HN, CS and positive control allopurinol groups. The HN group was intraperitoneally injected with 750 mg/kg oxonic acid potassium (OA), whereas the CS group was injected with OA along with a gavage of CS (low dose 3.125 g/kg, high dose 6.25 g/kg) for five weeks. For in vitro studies, uric acid-treated HK2 cells were used to verify the therapeutic mechanism of CS in HN. RESULTS: HN rats exhibit pathological phenotypes of elevated sUA levels and renal injury. CS significantly improved these symptoms and sUA (p < 0.05) and blood urea nitrogen (p < 0.01) levels, and dramatically improved renal tubular injury in HN rats. The IC50 value of UA (uric acid) in HK2 cells was 826.32 ± 3.55 µg/mL; however, 120 ng/mL CS had no significant cytotoxicity on HK2 cells. In vivo and in vitro studies showed that CS inhibited NF-κB phosphorylation and inhibited α-smooth muscle actin (α-SMA) and vimentin expression while increasing E-cadherin expression, suggesting that CS inhibited the fibrotic process in renal cells, thus protecting renal function. DISCUSSION AND CONCLUSIONS: These findings provide a fundamental understanding of the application of CS in HN treatment to better guide clinical interventions.

[Leonurine inhibits ferroptosis in renal tubular epithelial cells by activating p62/Nrf2/HO-1 signaling pathway].

To investigate the protective effect and the potential mechanism of leonurine(Leo) against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells), an in vitro erastin-induced ferroptosis model was constructed to detect the cell viability as well as the expressions of ferroptosis-related indexes and signaling pathway-related proteins. HK-2 cells were cultured in vitro, and the effects of Leo on the viability of HK-2 cells at 10, 20, 40, 60, 80 and 100 µmol·L~(-1) were examined by CCK-8 assay to determine the safe dose range of Leo administration. A ferroptosis cell model was induced by erastin, a common ferroptosis inducer, and the appropriate concentrations were screened. CCK-8 assay was used to detect the effects of Leo(20, 40, 80 µmol·L~(-1)) and positive drug ferrostatin-1(Fer-1, 1, 2 µmol·L~(-1)) on the viability of ferroptosis model cells, and the changes of cell morphology were observed by phase contrast microscopy. Then, the optimal concentration of Leo was obtained by Western blot for nuclear factor erythroid 2-related factor 2(Nrf2) activation, and transmission electron microscope was further used to detect the characteristic microscopic morphological changes during ferroptosis. Flow cytometry was performed to detect reactive oxygen species(ROS), and the level of glutathione(GSH) was measured using a GSH assay kit. The expressions of glutathione peroxidase 4(GPX4), p62, and heme oxygenase 1(HO-1) in each group were quantified by Western blot. RESULTS:: showed that Leo had no side effects on the viability of normal HK-2 cells in the concentration range of 10-100 µmol·L~(-1). The viability of HK-2 cells decreased as the concentration of erastin increased, and 5 µmol·L~(-1) erastin significantly induced ferroptosis in the cells. Compared with the model group, Leo dose-dependently increased cell via-bility and improved cell morphology, and 80 µmol·L~(-1) Leo promoted the translocation of Nrf2 from the cytoplasm to the nucleus. Further studies revealed that Leo remarkably alleviated the characteristic microstructural damage of ferroptosis cells caused by erastin, inhibited the release of intracellular ROS, elevated GSH and GPX4, promoted the nuclear translocation of Nrf2, and significantly upregulated the expression of p62 and HO-1 proteins. In conclusion, Leo exerted a protective effect on erastin-induced ferroptosis in HK-2 cells, which might be associated with its anti-oxidative stress by activating p62/Nrf2/HO-1 signaling pathway.

Novel gellan gum-based probiotic film with enhanced biological activity and probiotic viability: Application for fresh-cut apples and potatoes.

A novel probiotic film based on gellan gum (GN), cranberry extract (CE), and Lactococcus lactis (LA) was developed in the present study. The fluorescence and SEM image results showed that GN/CE film containing LA was successfully fabricated. The incorporation of LA significantly enhanced the antibacterial activity of the film. The presence of CE strengthened the antioxidant activity and LA survivability in the film. The combination of LA (0-1.0 %) and CE (0.5-1.0 %) improved the mechanical property of the film through the formation of density structure. The best comprehensive properties were obtained with the film containing 2.0 %LA and 0.5 %CE. The GN/2.0 %LA/0.5 %CE film also showed the optimal preservation effect on fresh-cut potatoes and apples. Hence, GN/2.0 %LA/0.5 %CE probiotic film has proved to be suitable for fruit and vegetable preservation.

What modulates the impacts of acid rain on the allelopathy of the two Asteraceae invasives?

Most of the allelopathic studies have focused on the independent allelopathy of one invasive plant, but have ignored the co-allelopathy of the two invasives. The variations in the type of acid rain can modulate the invasiveness of invasives via the changes in the allelopathy. Thus, it is vital to elucidate the allelopathy of invasives, particularly the co-allelopathy of the two invasives, under acid rain with different types, to illuminate the mechanisms driving the co-invasion of two invasives under diversified acid rain. However, little progress has been finished in this aspect presently. This study aimed to evaluate the co-allelopathy of two Asteraceae invasives Solidago canadensis L. and Erigeron annuus L. treated with acid rain with different nitrogen-to-sulfur ratios on seed germination and seedling growth of the horticultural Asteraceae species Lactuca sativa L. via a hydroponic experiment. Aqueous extracts of the two Asteraceae invasives generated obvious allelopathy on L. sativa. S. canadensis aqueous extracts caused stronger allelopathy. There may be an antagonistic effect for the co-allelopathy of the two Asteraceae invasives. Nitric acid at pH 5.6 weakened the allelopathy of the two Asteraceae invasives, but the other types of acid rain strengthened the allelopathy of the two Asteraceae invasives. The allelopathy of the two Asteraceae invasives increases with the increasing acidity of acid rain, but the allelopathy of the two Asteraceae invasives decreases with the increasing nitrogen-to-sulfur ratio of acid rain. Accordingly, the species number of invasives, and the acidity and type of acid rain modulated the impacts of acid rain on the allelopathy of the two Asteraceae invasives.

Effects of rosemary extract supplementation in feed on growth performance, meat quality, serum biochemistry, antioxidant capacity, and immune function of meat ducks.

This study aimed to investigate the effects of diets supplemented with different levels of rosemary extract (RE) on the growth performance, meat quality, serum biochemistry, antioxidative capacity, and immunological capacity of Cherry Valley meat ducks. A total of 525 healthy Cherry Valley female meat ducks at 1 d of age were selected for this study. Ducks were randomly divided into 5 treatments with 7 replicates per treatment, and each replicate had 15 ducks. All replicates were randomly assigned to treatments. The study was designed as a dose response experiment. Treatment 1 (CON) was fed with the basal diet, and Treatment 2 to 5 (RE250, RE500, RE750, RE1000) were fed with the basal diet supplemented with 250, 500, 750, and 1,000 g/t RE, respectively. The whole experiment lasted 42 days with early stage (1-21 d) and late stage (22-42 d). Results showed that during 22 to 42 d, ducks that were fed over 500 g/t RE had significantly lower feed gain ratio than the ones in CON (P = 0.006). In addition, ducks in RE750 had significantly lower L* and a* in leg muscle compared with the ones in CON (P < 0.05). Besides, ducks that were fed between 250 and 750 g/t RE had significantly lower total protein level in serum compared with the ones in CON (P = 0.005). Ducks in RE250 and RE750 had significantly lower albumin, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels in serum compared with the ones in CON and RE1000 (P < 0.05), and significant quadratic relationships were noticed between albumin, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol and dietary RE level (P < 0.05). Moreover, ducks that were fed between 500 and 750 g/t RE had significantly higher levels of interleukin-2 in serum compared to the ones in CON and RE1000 (P = 0.003). Ducks in RE250 and RE750 had significantly higher levels of immunoglobulin G in serum compared to the ones in CON and RE1000 (P < 0.001). Ducks that were fed over 500 g/t RE had significantly higher levels of immunoglobulin A in serum compared to the ones in CON (P = 0.001). Finally, ducks that were fed between 500 and 750 g/t RE had significantly higher serum levels of glutathione peroxidase, superoxide dismutase, catalase, and total antioxidant capacity (P < 0.05) compared to the ones in CON. Ducks that were fed over 250 g/t RE had significantly lower serum level of malondialdehyde compared to the ones in CON (P = 0.020). Collectively, dietary supplementation of RE improved the growth performance and meat qualities of meat ducks during 22 to 42 d, which were possibly associated with the antioxidative and anti-inflammatory effects of RE. Based on the serum antioxidative and immunological parameters, we suggested that 500 to 750 g/t was the optimal supplementation rate for RE in diets for meat ducks aged 22 to 42 d.

Holistic review and meta-analysis of independent impact of the residual SYNTAX score on prognosis in patients with acute coronary syndrome.

Objectives. The appropriate extent of revascularization following primary intervention is unknown. We conducted a systematic review and meta-analysis of residual Syntax score (rSS) to predict the outcomes and provide guide to optimal management of revascularization following primary intervention. Designs. Previously published studies from 2007 to 2020 assessing the prognostic impact of rSS after ACS were included for this meta-analysis. The primary endpoint was defined as the major adverse clinical events (MACE) in multivariable analysis. The risk ratios (RRs) with 95% confidence intervals (CI) were calculated using the RevMan 5.4 software. Results. A total of 8,157 participants complicated with ACS from 12 clinical studies were included in this analysis. Based on the wide range of rSS studies available, we classified it into two major groups: rSS < 8 and rSS ≥ 8. In multivariate analysis, the rSS was an independent risk marker for MACE [RR = 1.04 (95%CI; 1.00-1.08)], all-cause mortality [RR = 1.05 (1.03-1.07)] and cardiovascular death [RR = 1.05 (1.03-1.07)]. Patients with incomplete revascularization (ICR) showed higher prevalence of MACE along with all-cause mortality, cardiovascular morality, and recurrent myocardial infarction without significant heterogeneity [RR = 1.60 (1.03-1.07), 2.30 (1.57-3.38), 3.57 (2.09-6.10) and 1.70 (1.38-2.09), respectively]. The patients with rSS ≥ 8 presented higher frequency of all-cause mortality [RR = 2.99 (2.18-4.09)], cardiovascular death [RR = 3.32 (2.22-4.95)], and recurrent myocardial infarction [RR = 1.64 (1.34-2.02)]. Conclusion. The meta-analysis indicated that an rSS value of 8 could be a reasonable cut-off for incomplete revascularization after ACS and is an efficient tool to guide revascularization. In future, detailed research should focus on investigation of the optimal value of the rSS score.

Neferine Suppresses Experimental Colitis-Associated Colorectal Cancer by Inhibition of NF-[Formula: see text]B p65 and STAT3.

Colitis is an important risk factor for the development of colorectal cancer (CRC). The inhibitory effect and the underlying mechanism of neferine on colitis-associated colorectal cancer (CA-CRC) were investigated using an azoxymethane (AOM)/dextran sulfate sodium (DSS) triggered mice model. Compared with the CA-CRC model, oral treatment of neferine (2.5 and 5.0 mg/kg) significantly inhibited the DAI scores, decreased the tumor number, and reduced the tumor size. Neferine decreased inflammatory cell infiltration and epithelial hyperplasia in colon tissues. The levels of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text], interleukin-1beta (IL-1[Formula: see text], and interleukin 6 (IL-6) in colon tissues were decreased by neferine. Furthermore, neferine significantly decreased protein expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), p-p65, and p-STAT3 in both tumor and non-tumor tissues. In addition, neferine inhibited LPS and IL-6-induced phosphorylation of both NF-[Formula: see text]B p65 and STAT3. Molecular docking demonstrated the interactions of neferine with both NF-[Formula: see text]B p65 and STAT3. In conclusion, these results suggested that neferine inhibited CA-CRC carcinogenesis possibly by regulating NF-[Formula: see text]B and STAT3. Neferine might be a lead compound for the chemoprevention of CA-CRC.

Meroterpenoids with unknown skeletons from the leaves of Psidium guajava including one anti-inflammatory and anticoagulant compound: psidial F.

Four unknown meroterpenoids named as psidials D-G (1-4) together with 5 known compounds (5-9) had been obtained from the leaves of Psidium guajava. Their absolute structures were elucidated by spectral and calculated methods. Psidials DF (1-3) represented unknown carbon skeleton of the 3,5-diformylbenzyl phloroglucinol-coupled sesquiterpenoid. The possible biosynthetic pathway for 1-3 was postulated. In the bioactivity assay, psidial F (3) was found to possess anti-inflammatory and anticoagulant activities.

Prophylactic effects of hyperforin on anhedonia-like phenotype in chronic restrain stress model: A role of gut microbiota.

Anhedonia is the core symptom of depression, which largely reflects the therapeutic effect of depression. Hypericum perforatum is one of the most important antidepressant herb that has fewer side effects than traditional antidepressants. Considering the antibacterial effect of Hypericum perforatum, we verified whether this antidepressant activity was related to intestinal microbiomics. So we established anhedonia mouse model to explore the underlying treatment mechanism of hyperforin, the key antidepressant ingredient of Hypericum perforatum and to screen new psychobiotics based on hyperforin. It was found that hyperforin prevented anhedonia induced by chronic restraint stress in mice and altered the richness and evenness of bacteria populations compared with stressed mice. Metastat analysis showed that Akkermansia muciniphila and Muribaculum intestinale were the bacterial species obviously affected by hyperforin, and their abundance in hyperforin-treated group significantly increased. The results suggest that the effect of hyperforin on anhedonia may be partly assisted by Akkermansia muciniphila. These also indicate that Muribaculum intestinale may be another important intestinal bacteria involved in the pathogenesis of anhedonia symptom and depression.

Effect of Shenfu Injection () on Lactate and Lactate Clearance in Patients with Post-cardiac Arrest Syndrome: A Post Hoc Analysis of a Multicenter Randomized Controlled Trial.

OBJECTIVE: To assess the effects of Shenfu Injection (, SFI) on blood lactate, and secondarily its effect on the lactate clearance (LC) in patients with post cardiac arrest syndrome (PCAS). METHODS: The present study is a post hoc study of a randomized, assessor-blinded, controlled trial. Patients experienced in-hospital cardiac arrest between 2012 and 2015 were included in the predefined post hoc analyses. Of 1,022 patients enrolled, a total of 978 patients were allocated to the control group (486 cases) and SFI (492 cases) group, receiving standardized post-resuscitation care bundle (PRCB) treatment or PRCB combined with SFI (100 mL/d), respectively. Patients' serum lactate was measured simultaneously with artery blood gas, lactate clearance (LC) was calculated on days 1, 3, and 7 after admission and compared between groups. Lactate and LC were also compared between the survivors and non-survivors according to the 28-d mortality, as well as the survivors and non-survivors subgroups both in the SFI and control groups. RESULTS: In both groups, compared with pre-treatment levels, mean arterial pressure (MAP) and PaO2 were significantly improved on 1, 3, 7 d after treatment (P<0.05), while heart rate (HR) and blood glucose levels were significantly decreased on 1, 3 and 7 d after treatment (P<0.05). compared with control group, SFI treatment improved the values of MAP and PaO2 (P<0.05), and significantly decreased the levels of HR and the blood glucose level on 3 and 7 d after treatment (P<0.05). Compared with the control group, lactate levels decreased faster in the SFI group versus the control group on 3 and 7 d (P<0.05). From initiation of treatment and the following 3 and 7 d, SFI treatment greatly increased the LC compared with that in the control group (P<0.05). Compared with survivors, non-survivors had higher admission lactate levels (7.3 ±1.1 mmol/L vs. 5.5 ±2.3 mmol/L; P<0.01), higher lactate levels on days 1, 3 and 7 (P<0.05), and LC were decreased significantly on 3 and 7 d after treatment (P<0.05). Similar results were also found both in the SFI and control groups between survivors and non-survivors subgroups. CONCLUSION: SFI in combination with PRCB treatment is effective at lowering lactate level and resulted in increasing LC in a targeted population of PCAS patients.

Sanqi Oral Solution Mitigates Proteinuria in Rat Passive Heymann Nephritis and Blocks Podocyte Apoptosis via Nrf2/HO-1 Pathway.

Idiopathic membranous nephropathy (IMN) is the most common pathological type in adult nephrotic syndrome where podocyte apoptosis was found to mediate the development of proteinuria. Sanqi oral solution (SQ), an effective Chinese herbal preparation clinically used in treatment of IMN for decades, plays an important role in reducing proteinuria, but the underlying mechanisms have not been fully elucidated yet. The current study tested the hypothesis that SQ directly lessens proteinuria in IMN by reducing podocyte apoptosis. To investigate the effects of SQ, we established the experimental passive Heymann nephritis (PHN) rat model induced by anti-Fx1A antiserum in vivo and doxorubicin hydrochloride (ADR)-injured apoptotic podocyte model in vitro. SQ intervention dramatically reduced the level of proteinuria, together with the rat anti-rabbit IgG antibodies, complement C3, and C5b-9 deposition in glomerulus of PHN rats, accompanied by an elevation of serum albumin. Protein expression of synaptopodin, marker of podocyte injury, restored after SQ administration, whereas the electron microscopic analysis indicated that fusion of foot processes, and the pachynsis of glomerular basement membrane was markedly diminished. Further studies showed that SQ treatment could significantly inhibit podocyte apoptosis in PHN rats and ADR-injured podocytes, and protein levels of Cleaved Caspase-3 or the ratio of Bax/Bcl-2 were significantly decreased with SQ treatment in vivo or in vitro. Moreover, we found that the nuclear factor erythroid 2-related factor-2/heme oxygenase 1 (Nrf2/HO-1) pathway mediated the anti-apoptosis effective of SQ in podocyte. Thus, SQ mitigates podocyte apoptosis and proteinuria in PHN rats via the Nrf2/HO-1 pathway.

Identification of SPX family genes in the maize genome and their expression under different phosphate regimes.

Many studies have revealed that SPX (SYG1/Pho81/XPR1) family genes play a key role in signal transduction related to phosphorus (P) deficiency in plants. Here, we identified 33 SPX gene family members in maize through genome-wide analysis and classified them into 4 subfamilies according to SPX structural characteristics (SPX, SPX-MFS, SPX-EXS and SPX-RING). The promoter regions of ZmSPXs are rich in biotic/abiotic-related stress elements. The quantitative real-time PCR analysis of 33 ZmSPXs revealed that all members except for ZmSPX3 of the SPX subfamily were significantly induced under P-deficient conditions, especially ZmSPX4.1 and ZmSPX4.2, which showed strong responses to low P stress and exhibited remarkably different expression patterns in low Pi sensitive and insensitive cultivars of maize. These results suggested that the SPX subfamily might play pivotal roles in P stress sensing and response. Experimental observations of subcellular localization in maize protoplasts indicated the following results, implying multiple roles in cell metabolism: ZmSPX2, ZmSPX5 and ZmSPX6 localized in the nucleus; ZmSPX1 and ZmSPX3 localized in the nucleus and cytoplasm; and ZmSPX4.2 localized in the chloroplast. A Y2H assay suggested that ZmPHR1 could interact with ZmSPX3, ZmSPX4.2, ZmSPX5, and ZmSPX6, indicating the involvement of these proteins in the P stress response in a ZmPHR1-mediated manner.

Boosting Photothermal Theranostics via TICT and Molecular Motions for Photohyperthermia Therapy of Muscle-Invasive Bladder Cancer.

The development of photothermal agents with high photothermal conversion efficiency (PCE) can help to reduce drug and laser dosage, but still remains a big challenge. Herein, a novel approach is reported to design photothermal agents with high PCE values by promoting nonradiative heat generation processes through the cooperation of twisted intramolecular charge transfer (TICT) and molecular motions. Within the designed molecule 2DMTT-BBTD, the tetraphenylethenes act as molecular rotors, the long alkyl chain grafted thiophene helps to twist the molecular geometry to facilitate TICT state formation and preserve molecular motions in aggregate, while the strong electron-withdrawing BBTD unit enhances TICT effect. 2DMTT-BBTD exhibits NIR-absorption and a high PCE value of 74.8% under 808 nm laser irradiation. Gambogic acid (GA) which surmounts tumor cell thermotolerance by inhibiting heat shock protein 90 (HSP90) expression is coloaded into the nanoparticles, RGD peptide is further introduced to the nanoparticle surface to improve tumor accumulation. The resultant nanoparticles facilitate the effective low-temperature hyperthermia therapy of muscle-invasive bladder cancer (MIBC) with minimal damage to surrounding heathy tissues. This work delivers a new design concept for development of highly efficient photothermal agents, which also provides a safer approach for noninvasive treatment of MIBC and other malignant tumors.

Evaluation of serum antioxidative status, immune status and intestinal condition of Linwu duck challenged by lipopolysaccharide with various dosages and replications.

The present study investigated the dosage and replication effects of lipopolysaccharide challenges on the serum oxidative and immune status, and the intestinal morphology and permeability of Linwu ducks at the growing stage. A total of 500 54-day-old Linwu ducks were randomly assigned into 10 treatments, which included a factorial arrangement of 2 levels of LPS challenge replications (1 and 2 times) × 5 levels of lipopolysaccharide challenging dosages (0, 0.1, 0.2, 0.4, and 0.8 mg/kg). Each treatment consisted of 5 cages and 10 ducks per cage. The results showed significant replication effects of LPS on the body weight gain of ducks, that 2 replicates of LPS challenges significantly decreased the body weight gain than one challenge (P = 0.036). Regarding to the serum oxidative and immune status, dosage effects of lipopolysaccharide were found on the serum levels of superoxide dismutase (P = 0.034) and immunoglobulin A (P = 0.007), that 0.4 mg/kg lipopolysaccharides significantly increased the levels of these 2 parameters. Additionally, replication effects were found in the serum levels of interlukin 1ß, that 2 replicates of LPS challenges significantly increased the interlukin 1ß levels comparing to one challenge (P = 0.010). Regarding to the intestinal conditions, dosage effects of lipopolysaccharides were found on the ratio of villus height and crypt depth (P = 0.005) in duodenum, and the wall thickness of duodenum (P = 0.010) and jejunum (P = 0.001), that lipopolysaccharides at 0.1, 0.2, and 0.8 mg/kg significantly deteriorated the intestinal morphologies, especially in the duodenum and jejunum. Moreover, the dosage effects of lipopolysaccharides and the interactions of dosages and replications significantly influenced the permeabilities of the intestinal segments (P < 0.05). It appeared that 2 replicates of lipopolysaccharides at the dosage at 0.4 mg/kg could trigger oxidative and immunological stress, and damage the intestinal morphology and permeability of Linwu ducks at the growing stage.

Rhodomentosones A and B: Two Pairs of Enantiomeric Phloroglucinol Trimers from Rhodomyrtus tomentosa and Their Asymmetric Biomimetic Synthesis.

Rhodomentosones A and B (1 and 2), two pairs of novel enantiomeric phloroglucinol trimers featuring a unique 6/5/5/6/5/5/6-fused ring system were isolated from Rhodomyrtus tomentosa. Their structures with absolute configurations were elucidated by NMR spectroscopy, X-ray crystallography, and ECD calculation. The bioinspired syntheses of 1 and 2 were achieved in six steps featuring an organocatalytic asymmetric dehydroxylation/Michael addition/Kornblum-DeLaMare rearrangement/ketalization cascade reaction. Compounds 1 and 2 exhibited promising antiviral activities against respiratory syncytial virus (RSV).

Effectiveness of Chinese herbal medicine combined with Western medicine on deferring dialysis initiation for nondialysis chronic kidney disease stage 5 patients: a multicenter prospective nonrandomized controlled study.

BACKGROUND: In clinical practice, Chinese herbal medicine (CHM) purportedly has beneficial therapeutic effects for chronic kidney disease (CKD), which include delaying disease progression and dialysis initiation. However, there is a lack of high-quality evidence-based results to support this. Therefore, this study aimed to evaluate the efficacy of CHM combined with Western medicine in the treatment of stage 5 CKD. METHODS: This was a prospective nonrandomized controlled study. Stage 5 CKD (nondialysis) patients were recruited form 29 AAA class hospitals across China from July 2014 to April 2019. According to doctors' advice and the patients' wishes, patients were assigned to the CHM group (Western medicine + CHM) and the non-CHM group (Western medicine). Patient demographic data, primary disease, blood pressure, Chinese and Western medical drugs, clinical test results, and time of dialysis initiation were collected during follow-up. RESULTS: A total of 908 patients were recruited in this study, and 814 patients were finally included for further analysis, including 747 patients in the CHM group and 67 patients in the non-CHM group. 482 patients in the CHM group and 52 patients in the non-CHM group initiated dialysis. The median time of initiating dialysis was 9 (7.90, 10.10) and 3 (0.98,5.02) months in the CHM group and non-CHM group, respectively. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis [adjusted hazard ratio (aHR): 0.38; 95% confidence interval (CI): 0.28, 0.53] compared to those in the non-CHM group. After 1:2 matching, the outcomes of 160 patients were analyzed. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis (aHR: 0.32; 95% CI: 0.21, 0.48) compared to patients in the non-CHM group. Also, the Kaplan-Meier analysis demonstrated that the cumulative incidence of dialysis in the CHM group was significantly lower than that in the non-CHM group (log-rank test, P<0.001) before and after matching. CONCLUSIONS: This study suggest that the combination of CHM and Western medicine could effectively reduce the incidence of dialysis and delay the time of dialysis initiation in stage 5 CKD patients.