Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage.

Recurrent spontaneous miscarriage (RSM) affects 1%-2% of fertile women worldwide and poses a risk of future pregnancy complications. Increasing evidence has indicated that defective endometrial stromal decidualization is a potential cause of RSM. Here, we perform liquid chromatography with mass spectrometry (LC-MS)-based metabolite profiling in human endometrial stromal cells (ESCs) and differentiated ESCs (DESCs) and find that accumulated α-ketoglutarate (αKG) derived from activated glutaminolysis contributes to maternal decidualization. Contrarily, ESCs obtained from patients with RSM show glutaminolysis blockade and aberrant decidualization. We further find that enhanced Gln-Glu-αKG flux decreases histone methylation and supports ATP production during decidualization. In vivo, feeding mice a Glu-free diet leads to a reduction of αKG, impaired decidualization, and an increase of fetal loss rate. Isotopic tracing approaches demonstrate Gln-dependent oxidative metabolism as a prevalent direction during decidualization. Our results demonstrate an essential prerequisite of Gln-Glu-αKG flux to regulate maternal decidualization, suggesting αKG supplementation as a putative strategy to rectify deficient decidualization in patients with RSM.

Evaluation of physicochemical properties, bacterial community, and product fertility during rice straw composting supplemented with different nitrogen-rich wastes.

This study evaluated the compostability of rice straw as the main feedstock (75 % in dry weight), supplemented with three different nitrogen-rich wastes, namely food waste (FW), dairy manure (DM), and sewage sludge (SS). Organic matter (OM) degradation, maturity and fertility of the end-product, and bacterial community structure during the composting processes were compared. All composting processes generated mature end-product within 51 days. Notably, FW addition was more effective to accelerate rice straw OM degradation and significantly improved end-product fertility with a high yield of Chinese cabbage. The succession of the bacterial community was accelerated with FW supplementation. Genera Geobacillus, Chryseolinea, and Blastocatella were significantly enriched during the composting of rice straw with FW supplementation. Finally, temperature, total nitrogen, moisture, pH, and total carbon were the key factors affecting microorganisms. This study provides a promising alternative method to enhance the disposal of larger amounts of rice straw in a shorter time.

Magnetic hydrogel with long in situ retention time for self-regulating temperature hyperthermia.

Aim: Magnetic hydrogels (MHGs) have been proposed to avoid the redistribution and loss of magnetic nanoparticles (MNPs) when administrated by intratumoral injection. However, the requirement of complex cooling systems and temperature monitoring systems still hinder the clinical application of MHGs. This study investigates the feasibility of developing an MHG to realize the self-regulation of hyperthermia temperature. Methods: The MHG was developed by dispersing the MNPs with self-regulating temperature property into the temperature-sensitive hydrogel through physical crosslinking. The MHG's gelation temperature was tested by measuring the storage modulus and loss modulus on a rotational rheometer. The biocompatibility of the MHG and MNPs was characterized by CCK-8 assay against HaCaT cells. The in vivo magnetic heating property was examined through monitoring the temperature in the MHG on mice back upon the application of the alternating magnetic field (400 ± 5 Oe, 100 ± 5 kHz) every week for successive six weeks. Results: The gelation temperature of the MHG falls in 28.4°C-37.4°C. At in vivo applied concentration of 80 mg/mL, the MHG exhibits over 80% cell viability after 72 h, significantly higher than 50% cell viability of the MNPs (p<0.001). The MHG's stable magnetic hyperthermia temperatures in vivo are in the range of 43.4°C-43.8°C. Conclusions: The developed MHG can be injected using a syringe and will solidify upon body temperature. The biocompatibility is improved after the MNPs being made into MHG. The MHG can self-regulate the temperature for six weeks, exhibiting application potential for self-regulating temperature hyperthermia.

Postchemotherapy Histiocyte-rich Pseudotumor Mimicking Residual Lymphoma: A Report of 11 Cases Correlating Clinicopathologic and Radiologic Findings.

Postchemotherapy histiocyte-rich pseudotumor is a rare event in lymphoma patients and can cause elevated metabolic activity on positron emission tomography-computed tomography scan mimicking residual tumor. Here, we reported 11 lymphoma cases showing mass-like lesions with increased fluorodeoxyglucose uptake after chemotherapy. These postchemotherapy lesions occurred in various anatomic sites including spleen, mediastinum, lymph node, and other tissue locations, concerning for refractory or residual lymphoma. Their median size was 2.7 cm (range, 1.4 to 7.7 cm) and the median standardized uptake value on positron emission tomography-computed tomography was 10.6 (range, 5.2 to 13.8). Histologic examination of these lesions demonstrated reactive changes mainly composed of histiocyte-rich proliferation without viable lymphoma. Fat necrosis, cholesterol cleft, and calcium deposit were also commonly observed. After biopsies, 3 patients received additional chemotherapy, 2 had stem cell transplant with adjuvant chemotherapy or radiation, 1 had surgical excision, and the remaining 5 patients did not receive any further treatment. Follow-up imaging studies showed the resolved or decreased fluorodeoxyglucose activities in all patients including those without additional treatments, consistent with benign/reactive nature of these pseudotumor lesions. This study illustrates postchemotherapy mass-like lesions with elevated metabolic activity do not always represent residual disease and provides awareness of correlation between radiologic and histologic features of these lesions to avoid misinterpretation and overtreatment of lymphoma patients after chemotherapy.

High-resolution X-ray structure of three microtubule-stabilizing agents in complex with tubulin provide a rationale for drug design.

Microtubule is a key component of cytoskeleton and has been considered as an important target for the treatment of cancer. In particular, the tubulin taxane-site inhibitors such as taxol analogs and epothilones have achieved great success in clinical trials. However, the structural basis of many taxane-site inhibitors is still lacking in exploring their mechanism of action. We here reported crystal complex structures for three taxane-site inhibitors, Ixabepilone, Epothilone B, and Epothilone D, which were determined to 2.4 Å, 2.4 Å, and 2.85 Å, respectively. The crystal structures revealed that these taxane-site inhibitors possess similar binding modes to that of Epothilone A at the taxane site, e.g. making critical hydrogen-bonding interactions with multiple residues on the M-loop, which facilitating the tubulin polymerization. Furthermore, we summarized the binding modes of almost all taxane-site inhibitors and identified novel taxane-site ligands with simpler chemical structures through virtual screening. On this basis, new derivatives with higher binding affinity to tubulin were designed and developed, which can form additional hydrogen bond interactions with tubulin. Overall, this work determined the mechanism of action of epothilones and provided a structural basis to design reasonably novel taxane-site inhibitors with simpler structure and improved pharmacokinetic properties.

[Evaluation of the efficacy of acupuncture combined with hyperbaric oxygen on delayed neuropathological sequelae after carbon monoxide poisoning by using mTI-ASL imaging].

OBJECTIVE: Quantitative assessment of white blood flow in semi-oval center of patients with delayed neuropathological sequelae (DNS) after carbon monoxide poisoning treated with acupuncture combined with hyperbaric oxygen (HBO) based on magnetic resonance multi-inversion time arterial spin labeling imaging (mTI-ASL), and to evaluate its efficacy indirectly. METHODS: Twenty-six patients with clinically diagnosed DNS were randomly divided into an observation group (13 cases) and a control group (13 cases). The conventional therapy combined with HBO were given in the control group. In the observation group,on the base of the treatment, Xingnao Kaiqiao acupuncture was applied, the main acupoints were Shuigou (GV 26), Neiguan (PC 6), Baihui (GV 20), Shangxing (GV 23), Yintang (GV 29), Sanyinjiao (SP 6) on the affected side, Sishencong (EX-HN 1), Fenglong (ST 40), Lianquan (CV 23) and Jinjin (EX-HN12) for slurred speech, Jianyu (LI 15), Waiguan (TE 5) and Shousanli (LI 10) for upper limb pain, Huantiao (GB 30), Yanglingquan (GB 34), Yinlingquan (SP 9) for lower limb pain, the treatment was given once every day, 5 days as one course, with an interval of 2 days between the course. The treatment for 6 courses was required. The conventional head MR scan, mTI-ASL and diffusion tensor imaging (DTI) scans before and 1 week after treatment were adopted, Matlab (R2014b), Mricron and Syngo.via software were adopted to measure the cerebral blood flow (CBF) and anisotropy (FA) values of the semi-oval center. The correlation between the parameters was evaluated by Pearson method. And the simple intelligent mental state examination scale (MMSE) was uesd to assess cognitive function. RESULTS: After treatment, the CBF, MMSE scores in both groups and FA values in the observation group were higher than those before treatment (P<0.05). After treatment, the CBF, FA and MMSE scores in the observation group were significantly higher than those in the control group (P<0.05). There was a positive correlation between CBF, FA and MMSE scores (P<0.05), and the correlation between CBF and MMSE was the best (r =0.822). CONCLUSION: Acupuncture combined with hyperbaric oxygen can significantly improved early white matter hypoperfusion and improved cognitive function score in patients with DNS. The curative effect is better than that of hyperbaric oxygen therapy alone. The mTI-ASL imaging can quantitatively evaluate its curative effect.

Evaluation of the efficacy of acupuncture combined with hyperbaric oxygen on delayed neuropathological sequelae after carbon monoxide poisoning by using mTI-ASL imaging / 中国针灸

OBJECTIVE@#Quantitative assessment of white blood flow in semi-oval center of patients with delayed neuropathological sequelae (DNS) after carbon monoxide poisoning treated with acupuncture combined with hyperbaric oxygen (HBO) based on magnetic resonance multi-inversion time arterial spin labeling imaging (mTI-ASL), and to evaluate its efficacy indirectly.@*METHODS@#Twenty-six patients with clinically diagnosed DNS were randomly divided into an observation group (13 cases) and a control group (13 cases). The conventional therapy combined with HBO were given in the control group. In the observation group,on the base of the treatment, acupuncture was applied, the main acupoints were Shuigou (GV 26), Neiguan (PC 6), Baihui (GV 20), Shangxing (GV 23), Yintang (GV 29), Sanyinjiao (SP 6) on the affected side, Sishencong (EX-HN 1), Fenglong (ST 40), Lianquan (CV 23) and Jinjin (EX-HN12) for slurred speech, Jianyu (LI 15), Waiguan (TE 5) and Shousanli (LI 10) for upper limb pain, Huantiao (GB 30), Yanglingquan (GB 34), Yinlingquan (SP 9) for lower limb pain, the treatment was given once every day, 5 days as one course, with an interval of 2 days between the course. The treatment for 6 courses was required. The conventional head MR scan, mTI-ASL and diffusion tensor imaging (DTI) scans before and 1 week after treatment were adopted, Matlab (R2014b), Mricron and Syngo.via software were adopted to measure the cerebral blood flow (CBF) and anisotropy (FA) values of the semi-oval center. The correlation between the parameters was evaluated by Pearson method. And the simple intelligent mental state examination scale (MMSE) was uesd to assess cognitive function.@*RESULTS@#After treatment, the CBF, MMSE scores in both groups and FA values in the observation group were higher than those before treatment (<0.05). After treatment, the CBF, FA and MMSE scores in the observation group were significantly higher than those in the control group (<0.05). There was a positive correlation between CBF, FA and MMSE scores (<0.05), and the correlation between CBF and MMSE was the best ( =0.822).@*CONCLUSION@#Acupuncture combined with hyperbaric oxygen can significantly improved early white matter hypoperfusion and improved cognitive function score in patients with DNS. The curative effect is better than that of hyperbaric oxygen therapy alone. The mTI-ASL imaging can quantitatively evaluate its curative effect.

[Effects of temperature and pH on digestive enzymes activities in Whitmania pigra].

OBJECTIVE: Current study was conducted to investigate and compare the impact of temperature and pH on the activities of amylase, protease and lipase in alimentary tract of Whitmania pigra. METHOD: The responses of amylase, protease, and lipase activities were determined over a wide range of temperatures (7-52 degrees C) and pH gradient (2.2-11.2). RESULT: The highest lipase activity was found under 37 degrees C, pH 8.2, and the highest amylase activity was detected under 37 degrees C, pH 5.2, while protease activity peaked at 42 degrees C, pH 3.2 or pH 9.2. CONCLUSION: The optimal temperature in alimentary tract of Wh. pigra for lipase and amylase was 37 degrees C, and the responding temperature for protease was 42 degrees C. The optimal pH value in alimentary tract of Wh. pigra for lipase and amylase was pH 8.2 and pH 5.2, respectively. While pH 3.2 or 9.2 seems to be both favorable for high protease activity.

Trafficking-competent KCNQ1 variably influences the function of HERG long QT alleles.

BACKGROUND: Mutations in the KCNQ1 and human ether-a-go-go-related gene (HERG) genes cause the long QT syndromes, LQTS1 and LQTS2, due to reductions in the cardiac repolarizing I(Ks) and I(Kr) currents, respectively. It was previously reported that KCNQ1 coexpression modulates HERG function by enhancing membrane expression of HERG, and that the 2 proteins coimmunoprecipitate, and colocalize in myocytes. In vivo studies in genetically modified rabbits also support a HERG-KCNQ1 interaction. OBJECTIVE: We sought to determine whether KCNQ1 influences the current characteristics of HERG genetic variants. METHODS: This study used expression of HERG and KCNQ1 wild-type (WT) and mutant channels in heterologous systems, combined with whole-cell patch clamp analysis and biochemistry. RESULTS: Supporting the notion that KCNQ1 needs to be trafficking competent to influence HERG function, we found that although the tail current density of HERG expressed in Chinese Hamster Ovary (CHO) cells was approximately doubled by WT KCNQ1 coexpression, it was not altered in the presence of the trafficking-defective KCNQ1(T587M) variant. Activation and deactivation kinetics of HERG variants were not altered. The HERG(M124T) variant, previously shown to be mildly impaired functionally, was restored to WT levels by KCNQ1-WT but not KCNQ1(T587M) coexpression. The tail current densities of the severely trafficking-impaired HERG(G601S) and HERG(F805C) variants were only slightly improved by KCNQ1 coexpression. The trafficking competent but incompletely processed HERG(N598Q), and a mutation in the selectivity filter, HERG(G628S), were not improved by KCNQ1 coexpression. CONCLUSION: These findings suggest a functional codependence of HERG on KCNQ1 during channel biogenesis. Moreover, KCNQ1 variably modulates LQTS2 mutations with distinct underlying pathologies.