The effect of progesterone supplementation for luteal phase support in natural cycle frozen embryo transfer: a systematic review and meta-analysis based on randomized controlled trials.

IMPORTANCE: The necessity of progesterone supplementation for luteal phase support (LPS) in natural cycle frozen embryo transfer (NC-FET) cycles warrants further confirmation. OBJECTIVE: To investigate the effect of progesterone supplementation for LPS on the reproductive outcomes of patients undergoing NC-FET cycles. DATA SOURCES: The PubMed, Ovid-Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM were electronically searched. The search time frame was from inception up to September 2022. STUDY SELECTION AND SYNTHESIS: Randomized controlled trials (RCTs) that used progesterone for LPS in NC-FET cycles, including true NC-FET cycles (tNC-FET) and modified NC-FET cycles (mNC-FET), were included. The counted data were analyzed using relative risk (RR) as the effect-size statistic, and each effect size was assigned its 95% confidence interval (CI). MAIN OUTCOME MEASURES: The primary outcomes were the live birth rate (LBR) and the clinical pregnancy rate (CPR), and the secondary outcome was the miscarriage rate. RESULTS: Four RCTs were included, which involved 1116 participants. The results of the meta-analysis showed that progesterone supplementation was associated with increased LBR (RR, 1.42; 95% CI, 1.15-1.75; I2 = 0%, moderate-quality evidence) and CPR (RR, 1.30, 95% CI, 1.07-1.57; I2 = 0%, moderate-quality evidence) in patients undergoing NC-FET cycles. Subgroup analysis showed that progesterone supplementation was associated with higher LBR and CPR in tNC-FET cycles. However, no association was found between increased LBR and CPR in mNC-FET cycles. In addition, only one RCT reported that oral dydrogesterone had similar CPR and miscarriage rate compared with vaginal progesterone in mNC-FET cycles. CONCLUSION(S): Overall, moderate-quality evidence suggested that progesterone supplementation for LPS was associated with increased LBR and CPR in NC-FET cycles. Progesterone supplementation was associated with a higher LBR and CPR in tNC-FET cycles. However, the effectiveness of progesterone supplementation in mNC-FET cycles should be further verified by larger RCTs. Low to very low-quality evidence indicated that oral dydrogesterone and vaginal progesterone have similar reproductive outcomes in mNC-FET cycles, which requires further study, especially in tNC-FET cycles. REGISTRATION NUMBER: PROSPERO CRD42022355550 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=355550) was registered on September 3, 2022.

Aspergillus niger Enhances Organic and Inorganic Phosphorus Release from Wheat Straw by Secretion of Degrading Enzymes and Oxalic Acid.

To explore the mechanisms of crop straw degradation and phosphorus (P) release by phosphate-solubilizing fungi (PSF), a typical PSF Aspergillus niger (A. niger, ANG) was investigated for the degradation of wheat straw (WST) in this work. The results revealed that A. niger significantly increased wheat straw degradation (30%) compared with no A. niger treatment (7.7%). Meanwhile, more than 92% of total P was released from WST by A. niger, much higher than from WST treatment (69.5%). Although the ratios of inorganic P release between WST and WST + ANG treatments were similar (17.6 vs 19.7%), a significant difference occurred between their release of organic P, i.e., WST (51.9%) vs WST + ANG (72.5%). The high enzyme activity of ß-1,4-glucanase and ß-glucosidase produced by A. niger contributed to the wheat straw degradation and organic P release compared with no A. niger treatment. Oxalic acid secreted by A. niger dominated the release of inorganic P from WST. Our findings suggested that A. niger is an efficient microbial agent for crop straw degradation and P release, which could be a candidate in the pathway of straw return.

Effect of inoculation with Penicillium chrysogenum on chemical components and fungal communities in fermentation of Pu-erh tea.

Developing an effective method to improve the quality of Pu-erh tea is of great scientific and commercial interest. In this work, Penicillium chrysogenum P1 isolated from Pu-erh tea was inoculated in sterilized or unsterilized sun-dreid green tea leaves to develop pure-culture fermentation (PF) and enhanced fermentation (EF) of Pu-erh tea. Spectrophotometry and high performance liquid chromatography determined that contents of free amino acids (FAA), total tea polyphenols and eight polyphenolic compounds in PF were significantly lower than these in non-inoculation control test (CK) (P < 0.05), whereas the contents of soluble sugars and theabrownins (TB) in PF were significantly higher (P < 0.05) than in CK. A total of 416 volatile compounds were detected by headspace solid-phase micro-extraction combined with gas chromatography-mass spectrometry. Comparison to CK, 124 compounds in PF were degraded or decreased significantly [Variable importance in projection [(VIP) > 1.0, P < 0.05, fold change (FC) < 0.5], whereas 110 compounds in PF were formed or increased significantly (VIP > 1.0, P < 0.05, FC > 2). Compared with normal fermentation (NF), the levels of gallic acid, (+)-catechin, (-)-epicatechin and 64 volatile compounds in EF were significantly lower (VIP > 1.0, P < 0.05, FC < 0.5), whereas the levels of FAA and 39 volatile compounds were significantly higher (VIP > 1.0, P < 0.05, FC > 2). Amplicon sequencing of fungal internal transcribed spacer 1 (ITS1) revealed that P. chrysogenum P1 didn't become the dominant fungus in EF; while the fungal communities in EF were different from those in NF, in that the relative abundances of Blastobotrys bambusae and P. chrysogenum in EF were higher, and the relative abundances of Aspergillus niger and Kluyveromyces marxianus in EF were lower. Overall, inoculation of P. chrysogenum in unsterilized sun-dreid green tea leaves changed the the fungal communities in fermentation of Pu-erh tea, and chemical compounds in fermented tea leaves, i.e., the levels of TB and the compounds responsible for the stale flavor, e.g., 2-amino-4-methoxybenzothiazole were increased, resulting in improvement of the sensory quality, including mellower taste and stronger stale flavor.

Tracing Key Molecular Regulators of Lipid Biosynthesis in Tuber Development of Cyperus esculentus Using Transcriptomics and Lipidomics Profiling.

Cyperus esculentus is widely representing one of the important oil crops around the world, which provides valuable resources of edible tubers called tiger nut. The chemical composition and high ability to produce fats emphasize the role of tiger nut in promoting oil crop productivity. However, the underlying molecular mechanism of the production and accumulation of lipids in tiger nut development still remains unclear. Here, we conducted comprehensive transcriptomics and lipidomics analyses at different developmental stages of tuber in Cyperus esculentus. Lipidomic analyses confirmed that the accumulation of lipids including glycolipids, phospholipids, and glycerides were significantly enriched during tuber development from early to mature stage. The proportion of phosphatidylcholines (PC) declined during all stages and phosphatidyl ethanolamine (PE) was significantly declined in early and middle stages. These findings implied that PC is actively involved in triacylglycerol (TAG) biosynthesis during the tubers development, whereas PE may participate in TAG metabolism during early and middle stages. Comparative transcriptomics analyses indicated several genomic and metabolic pathways associated with lipid metabolism during tuber development in tiger nut. The Pearson correlation analysis showed that TAG synthesis in different developmental stages was attributed to 37 candidate transcripts including CePAH1. The up-regulation of diacylglycerol (DAG) and oil content in yeast, resulted from the inducible expression of exogenous CePAH1 confirmed the central role of this candidate gene in lipid metabolism. Our results demonstrated the foundation of an integrative metabolic model for understanding the molecular mechanism of tuber development in tiger nut, in which lipid biosynthesis plays a central role.

Effect of Parathyroid Hormone on Intestinal Mucosal Sodium Dependent Phosphorus Transporter.

INTRODUCTION: Hyperphosphatemia is an important symptom of chronic kidney disease-mineral bone disorder (CKD-MBD). Various oral phosphate binders have been used, but have not been very effective, especially for severe secondary hyperparathyroidism (SHPT) in patients undergoing maintenance dialysis. Maintenance dialysis patients with severe SHPT can develop hypophosphatemia for several months after parathyroidectomy without elevated alkaline phosphatase. Based on these clinical phenomena, we hypothesized that high levels of parathyroid hormone (PTH) might inhibit intestinal phosphorus absorption which mediated by sodium-dependent phosphorus transporters. METHODS: Forty BALB/c mice were divided into four groups. Mice in group 1 were given an intravenous injection of normal saline as the control group. Mice in groups 2, 3, and 4 were given PTH(1- 34) in doses of 40 µg/100 g, 200 µg/100 g, and 400 µg/100 g body weight intravenously, respectively. All mice were euthanized 8 hours after the injection. The mRNA and protein expression of sodium-dependent phosphorus transporter NPT-2b and Pit-1 on the membrane of the intestinal epithelial cells was detected by real-time polymerase chain reaction (PCR) and western blot analysis, respectively. RESULTS: In group 4, intestinal epithelial NPT-2b and Pit-1 protein expression was significantly decreased, whereas in groups 2 and 3, no significant changes were found. CONCLUSION: A high PTH level decreases the protein expression of NPT-2b and Pit-1 in the intestinal mucosa.

Ginsenoside-Rg1 Rescues Stress-Induced Depression-Like Behaviors via Suppression of Oxidative Stress and Neural Inflammation in Rats.

Depression is an inflammatory-related condition, with the progression in neuronal damage resulting in major depression disorder. Ginsenoside-Rg1, a sterol extract from the herb Panax ginseng, has been shown to exert neuroprotective effects upon neurodegeneration disorders. However, whether ginsenoside-Rg1 confers antidepressant-like effects on neuroinflammation as associated with depression, as well as the possible mechanism involved in these neuroprotective effects, is currently unclear. In the present report, we show that treatment with ginsenoside-Rg1 (40 mg/kg, i.p.) significantly ameliorated depressive-like behaviors as induced by chronic unpredictable mild stress (CUMS) in a rat model of depression. Moreover, these CUMS rats treated with ginsenoside-Rg1 showed reductions in the levels of the oxidative stress products and the activity in the antioxidant stress kinase. Furthermore, CUMS rats treated with ginsenoside-Rg1 showed ameliorated neuroinflammation and associated neuronal apoptosis along with a reduction in dendritic spine atrophy and display of depressive behaviors. Taken together, the results of this study suggest that ginsenoside-Rg1 produces antidepressant-like effects in CUMS-exposed rats; and one of the mechanisms for these antidepressant-like effects of ginsenoside-Rg1 appears to involve protection against oxidative stress and thus the neuronal deterioration resulting from inflammatory responses. These findings provide evidence for the therapeutic potential of ginsenoside-Rg1 in the treatment of stress-related depression.

Effects of Herba Lophatheri extract on the physicochemical properties and biological activities of the chitosan film.

Active films based on chitosan incorporated Herba Lophatheri extract (HLE) with different concentrations were developed. Physicochemical properties of the chitosan films incorporated HLE, including density, opacity, moisture content, color, water solubility, swelling, water vapor permeability and oil resistance were measured. Biological activities of the films include antioxidant activity and antimicrobial properties, which were characterized in terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity and Oxford cup method, respectively. The potential interactions between chitosan and HLE in the films were investigated by Attenuated total reflectance-Fourier transform infrared analysis and X-ray diffraction. The results indicated that the moisture content, water solubility, swelling degree, water vapor permeability and oil absorption rate of chitosan/HLE films decreased up to 14.81%, 38.97%, 48.03%, 69.23% and 80% in comparison with the control chitosan film. The DPPH free radical scavenging activity of chitosan/HLE films increased by nearly 3.5 folds, and the diameter of inhibitory zone of the chitosan/HLE films extract solution against Staphylococcus aureus and Escherichia coli increased 17.02% and 19.28%, respectively. Additionally, the incorporation of HLE caused interactions between chitosan and HLE and gave rise to the chitosan/HLE films more opacity, darker, redness and yellowness appearance. In summary, the addition of HLE enhanced the moisture and oil resistance, antioxidant activity which declined with time, and antimicrobial activity of the chitosan film, which were all desirable for food packaging.

Bone marrow mesenchymal stem cell-derived exosomes alleviate high phosphorus-induced vascular smooth muscle cells calcification by modifying microRNA profiles.

Vascular calcification is a common complication in patients with chronic kidney disease (CKD). It is an important predictor of cardiovascular disease and all-cause mortality. Previous studies have confirmed that bone marrow mesenchymal stem cell (BMSC) therapy can reduce vascular calcification, but the specific mechanism is still controversial. In this study, we aimed to investigate the mechanisms of BMSC-derived exosomes (EXO) in improving vascular calcification. BMSCs were cultured and EXO were isolated using the Total Exosome Isolation Reagent. Human aortic vascular smooth muscle cells (HA-VSMCs) were cultured into three groups: control group, high phosphorus group, and high phosphorus plus EXO group. Then, indicators related to smooth muscle cell calcification and microRNA profiles were analyzed. BMSC-derived exosomes inhibited high phosphorus-induced calcification in HA-VSMCs. Besides, EXO treatment reduced calcium content and decreased the alkaline phosphatase (AKP) activity in high phosphorus co-incubated HA-VSMCs. MicroRNA (miRNA) and mRNA expression profiles analyses revealed that 63 miRNAs were significantly upregulated and 1424 genes were significantly downregulated in HA-VSMCs after EXO treatment. Functional miRNA-gene regulatory network revealed that mTOR, MAPK, and Wnt signaling pathway were involved in vascular calcification. BMSC-derived exosomes alleviated high phosphorus-induced calcification in HA-VSMC through modifying miRNA profiles.

[Effect of Scalp Electroacupuncture Combined Constraint-induced Movement Therapy on Move- ment Function of Ischemic Stroke Patients' Upper Limbs].

Objective To observe the effects of scalp electroacupuncture (SEA) combined con- straint-induced movement therapy ( CIMT) on movement function of ischemic stroke patients' upper limbs. Methods Totally 80 stroke patients were assigned to four groups according to random digit table, i.e., the routine rehabilitation group, the SEA group, the CIMT group, and the comprehensive intervention group. Patients in the routine rehabilitation group strengthened the training of upper limbs on the affected side by Bobath dominated technology and Brunnstrom assisted technology. Patients in the SEA group received Jiao's SEA combined EA therapy. Those in the CIMT group restricted the upper limbs of the healthy side and strengthened training of the affected side. Those in the comprehensive intervention group used SEA combined CIMT treatment. Fugl-Meyer assessment scale (FMA) , grading of hand function and range of wrist movement were observed before intervention, at week 4 and 12 after intervention, respectively. Results Compared with before treatment in the same group, FMA scores of upper limbs significantly increased, grading of hand function, and range of wrist movement were obviously improved in the 4 groups after 4-week treatment (P <0. 05, P <0. 01). There was no statistical difference in FMA scores of upper limbs or grading of hand function among the four groups. But dorsal expansion of wrist and radial deviation were more obviously improved in the comprehensive intervention group than in the routine rehabilitation group (P <0. 05). Compared with the routine rehabilitation group, FMA scores of up- per limbs increased, grading of hand function and range of wrist movement were obviously improved in the comprehensive intervention group (P <0. 05). Conclusions Routine rehabilitation, SEA, and CIMT showed better rehabilitation effect on movement function of ischemic stroke patients' upper limbs. But ESA combined CIMT showed most obvious effect with earliest effect shown.

Efficacy of microwave ablation for severe secondary hyperparathyroidism in subjects undergoing hemodialysis.

Severe secondary hyperparathyroidism (SHPT) is a serious problem in patients undergoing hemodialysis. The efficacy and safety of microwave ablation (MWA), a minimally invasive treatment, for severe SHPT are as yet unclear. To clarify the role of MWA, we administered it to patients with severe SHPT and assessed its efficacy and safety. This was a prospective, single-center, single-arm, clinical trial. We enrolled patients with severe SHPT attending our hemodialysis center who met the inclusion and exclusion criteria. We then assessed primary outcome measures (serum concentrations of intact parathyroid hormone) and secondary outcome measures (serum concentrations of calcium and phosphorus). Twenty-six patients were enrolled in this study, 10 of whom (38.46%) were responsive to MWA and 16 (61.54%) of whom were not. The main complication was hypocalcemia (10 cases, 38.46%), which had occurred in all cases by one week after administration of MWA. Responding patients with hypocalcemia all achieved normal serum calcium concentrations within seven months and non-responding patients within three months. There were no changes in serum phosphorus concentrations after MWA in either responders or non-responders. Microwave ablation is relatively ineffective in patients with severe SHPT undergoing maintaining hemodialysis and should not be the initial therapy in such cases.

A mismatch negativity study in Mandarin-speaking children with sensorineural hearing loss.

OBJECTIVE: a) To examine the effects of sensorineural hearing loss on the discriminability of linguistic and non-linguistic stimuli at the cortical level, and b) to examine whether the cortical responses differ based on the chronological age at intervention, the degree of hearing loss, or the acoustic stimulation mode in children with severe and profound hearing loss. METHODS: Mismatch negativity (MMN) responses were collected from 43 children with severe and profound bilateral sensorineural hearing loss, and 20 children with normal hearing (age: 3-6 years). In the non-verbal stimulation condition, pure tones with frequencies of 1 kHz and 1.1 kHz were used as the standard and the deviant respectively. In the verbal stimulation condition, the Chinese mandarin tokens/ba2/and/ba4/were used as the standard and the deviant respectively. Latency and amplitude of the MMN responses were collected and analyzed. RESULTS: Overall, children with hearing loss showed longer latencies and lower amplitudes of the MMN responses to both non-verbal and verbal stimulations. The latency of the verbal/ba2/-/ba4/pair was longer than that of the nonverbal 1 kHz-1.1 kHz pair in both groups of children. CONCLUSIONS: Children with hearing loss, especially those who received intervention after 2 years of age, showed substantial weakness in the neural responses to lexical tones and pure tones. Thus, the chronological age when the children receive hearing intervention may have an impact on the effectiveness of discriminating between verbal and non-verbal signals.

Apelin: A novel inhibitor of vascular calcification in chronic kidney disease.

BACKGROUND: Vascular calcification (VC) is closely related to cardiovascular events in chronic kidney disease (CKD). Apelin has emerged as a potent regulator of cardiovascular function, but its role in VC during CKD remains unknown. We determined whether apelin plays a role in phosphate-induced mineralization of human aortic smooth muscle cells (HASMCs) and in adenine-induced CKD rats with aortic calcification. METHODS AND RESULTS: In vitro, apelin-13 was found to inhibit calcium deposition in HASMCs (Pi(+) Apelin(+) group vs Pi(+) Apelin(-) group: 50.1 ± 6.21 ug/mg vs 146.67 ± 10.02 ug/mg protein, p = 0.012) and to suppress the induction of the osteoblastic transformation genes BMP-2, osteoprotegerin (OPG) and Cbfa1. This effect was mediated by interference of the sodium-dependent phosphate cotransporter (Pit-1) expression and phosphate uptake. In vivo, decreased plasma apelin levels (adenine(+) apelin(-) vs vehicle: 0.37 ± 0.09 ng/ml vs 0.68 ± 0.16 ng/ml, p = 0.003) and downregulation of APJ in the aorta were found in adenine-induced CKD rats with hyperphosphatemia (adenine(+) apelin(-) vs vehicle: 6.91 ± 0.23 mmoL/L vs 2.3 ± 0.07 mmoL/L, p = 0.001) and aortic calcification. Exogenous supplementation of apelin-13 normalized the level of the apelin/APJ system and significantly ameliorated aortic calcification, as well as the suppression of Runx2, OPG and Pit-1 expression. CONCLUSIONS: Apelin ameliorates VC by suppressing osteoblastic differentiation of VSMCs through downregulation of Pit-1. These results suggest apelin may have potential therapeutic value for treatment of VC in CKD.

A novel cyclic dipeptide from deep marine-derived fungus Aspergillus sp. SCSIOW2.

A novel cyclic dipeptide, 14-hydroxy-cyclopeptine (1), was purified from a deep sea derived fungal isolate identified as an Aspergillus sp. The structure was elucidated by detailed spectroscopic analyses using 1D and 2D NMR experiments and high resolution mass spectrometry. The absolute configuration of the amino acid was determined by Marfey's method. Two conformational isomers of 1 were established by ROE analyses. 1 inhibited nitric oxide production with IC50 values at 40.3 µg/mL in a lipopolysaccharide and recombinant mouse interferon-γ -activated macrophage-like cell line, RAW 264.7 and showed no cytotoxic effect in the tested dose range up to 100 µg/mL.

Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice.

Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2(-/-) mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-ß) and IL-6. Particularly, a dose-dependent inhibition on LPS-induced inflammatory responses was observed following treatment with MBF dichloromethane extract (MBF-DE), in which linoleic acid and ethyl linolenate were identified as two active compounds. Moreover, we elucidated that MBF-DE attenuated LPS-induced inflammatory responses by blocking activation of both NF-κB/p65 and pERK/MAPK pathways. In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage. In addition, MBF-fed MUC2(-/-) mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group. Overall, our results demonstrated that MBF suppressed the development of intestinal inflammation and tumorgenesis both in vitro and in vivo, and supports the potential of MBF as a therapeutic functional food for testing in human clinical trials.

Melatonin prevents neural tube defects in the offspring of diabetic pregnancy.

Melatonin, an endogenous neurohormone secreted by the pineal gland, has a variety of physiological functions and neuroprotective effects. However, its protective role on the neural tube defects (NTDs) was not very clear. The aim of this study was to investigate the effects of melatonin on the incidence of NTDs (including anencephaly, encephalocele, and spina bifida) of offspring from diabetic pregnant mice as well as its underlying mechanisms. Pregnant mice were given 10 mg/kg melatonin by daily i.p. injection from embryonic day (E) 0.5 until being killed on E11.5. Here, we showed that melatonin decreased the NTDs (especially exencephaly) rate of embryos exposed to maternal diabetes. Melatonin stimulated proliferation of neural stem cells (NSCs) under hyperglycemic condition through the extracellular regulated protein kinases (ERK) pathway. Furthermore, as a direct free radical scavenger, melatonin decreased apoptosis of NSCs exposed to hyperglycemia. In the light of these findings, it suggests that melatonin supplementation may play an important role in the prevention of neural malformations in diabetic pregnancy.

Anthocyanin-rich fractions from red raspberries attenuate inflammation in both RAW264.7 macrophages and a mouse model of colitis.

Edible berries have a broad spectrum of biomedical functions, including improving immune responses and reducing risk for chronic diseases. In this study, the anti-inflammatory activities of crude extracts (CEs), anthocyanin-rich fractions (ARFs), and des-anthocyanin fractions (DAFs) from seven berries were evaluated based on their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)/IFN-γ-activated RAW264.7 macrophages. ARFs from red raspberries (RR-ARFs) exhibited the highest efficiency in suppressing NO synthesis. The anti-inflammatory properties were also demonstrated by reducing the expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1ß) and IL-6 in RAW264.7 cells. The luciferase reporter assay demonstrated that the activities of NF-κB and AP-1 signaling pathways were significantly suppressed by RR-ARFs. Further studies showed that RR-ARFs decreased the phosphorylation of IKK, IκBα, p65 and JNK and the nuclear translocation of p65 in LPS/IFN-γ-stimulated RAW264.7 cells. In a mouse colitis model, dextran sulfate sodium (DSS)-induced weight loss and histological damage were significantly ameliorated by RR-ARFs treatment. Taken together, our results indicate that RR-ARFs attenuate inflammation both in vitro and in vivo primarily by inhibiting the activation of NF-κB and MAPKs. The anti-inflammatory of RR-ARFs could be harnessed and applied in animal agriculture, drug and food industries.

Is the dialysate calcium concentration of 1.75 mmol/L suitable for Chinese patients on maintenance hemodialysis?

We studied the effects of increasing the dialysate calcium concentration (DCa) to 1.75 mmol/L on controlling chronic kidney disease-mineral and bone disorder in Chinese patients on maintenance hemodialysis (MHD). We reviewed the data of MHD patients in one center (cohort 1) during prior 10 years and analyzed the risk factors of mortality and transference calcification (TC) in120 MHD patients surviving in 2003 (cohort 2). A multicenter, prospective, parallel-group, controlled trial (cohort 3) was also conducted from January 2011 to December 2012. The DCa at one center was increased from 1.5 to 1.75 mmol/L but was not changed at the other two centers. The clinical outcomes, biochemical parameters, medicine treatments, and TC markers [aortic arch calcification score (AoACS)] were compared between groups. In cohort 1, the annual mean serum iPTH increased significantly over 10 years. In cohort 1, 72 patients survived for 10 years, whose doses of calcium salts and active vitamin D3 and AoACs increased progressively. In cohort 2, the main cause of death was cardiocerebrovascular disease (CCVD) (n = 18, 48.6 %). Male sex and lower serum calcium concentrations were independent risk factors for CCVD mortality. In cohort 3, serum phosphorus, iPTH, and 25(OH)D decreased and serum calcium increased significantly; also, the doses of calcium and vitamin D3 decreased from 2011 to 2012 in the DCa 1.75 group. There were no significant differences in clinical outcomes either between groups or between the two calendar years. Our results indicate that increasing DCa to 1.75 mmol/L can decrease the elevated levels of serum iPTH and phosphorus, reduce the doses of calcium and vitamin D3, and be safe for short periods of time.

Dual-index evaluation of character changes in Panax ginseng C. A. Mey stored in different conditions.

Panax ginseng C. A. Mey has been used as a traditional medicine and functional food in Asia for thousands of years for its improvement of human immunity and metabolism and its antitumor and antifatigue activities. This study reports the impact of storage conditions and storage period on the quality of P. ginseng. The contents of four major ginsenosides in P. ginseng and phosphorylation activities of Akt of ginseng extracts were affected by both storage conditions and storage period. In contrast, the ATP generation capacity of ginseng extracts was affected by storage conditions, but not by storage period. The results showed that the quality of P. ginseng could be well maintained at a relative humidity between 70% and 90%, and dry conditions might decrease the quality of P. ginseng. Through dual-index evaluation, the present study extended our knowledge on the changes of ginsenosides and bioactivities in P. ginseng with respect to different storage conditions and storage periods.

Discovery of new potent inhibitors for carbonic anhydrase IX by structure-based virtual screening.

Through structure-based virtual screening, some dozen of benzene sulfonamides with novel scaffolds are identified as potent inhibitors against carbonic anhydrase (CA) IX with IC50 values ranging from 2.86 to 588.34 nM. Among them, compounds 1 and 9 show high selectivity against tumor-target CA IX over CA II (the selectivity ratios are 21.3 and 136.6, respectively). The possible binding poses of hit compounds are also explored and the selectivity is elucidated by molecular docking simulations. The hit compounds discovered in this work would provide novel scaffolds for further hit-to-lead optimization.

Jatropholane-type diterpenes from Euphorbia sikkimensis.

Four new jatropholane-type diterpenes (1-4), named sikkimenoids A-D, were isolated from the aerial parts of Euphorbia sikkimensis. The structural elucidations of 1-4 were accomplished by extensive NMR analyses, and their absolute configurations were established by ECD calculations. Compound 2 exhibited weak antiangiogenic activity with an IC(50) value of 43.0 µM when evaluated using a zebrafish model.