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To investigate the renal microstructure changes and hypoxia changes in type 2 diabetic patients and the relationship between them and glucose using both diffusion-weighted imaging (DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI). After measuring morning fasting blood glucose, DWI and BOLD MRI were performed in 57 patients with type 2 diabetes mellitus (DM group) and 14 healthy volunteers (NC group). According to the fasting blood glucose levels, diabetic patients were divided into a normoglycemic diabetes group (group A), a less hyperglycemic diabetes group (group B) and a more hyperglycemic diabetes group (group C). The renal parenchymal apparent diffusion coefficient (ADC), renal cortical R2* (CR2*), and medullary R2* (MR2*) were measured, and the R2* ratio between the medulla and cortex (MCR) was calculated. To test for differences in ADC, R2*, and MCR among the four groups, the data were analyzed by separate one-way ANOVAs. The correlations between ADC, R2*, and MCR and the clinical index of renal function were analyzed. Groups B and C had significantly lower ADC values in the renal parenchyma (P = 0.048, 0.002) and significantly higher MR2* and MCR values (P

Receptor interacting serine/threonine protein kinase 1 (RIPK1) activation and necroptosis have been genetically and mechanistically linked with human multiple sclerosis and neurodegenerative diseases for which demyelination is a common key pathology. Demyelination can be healed through remyelination which is mediated by new oligodendrocytes derived from the adult oligodendrocyte progenitor cells (OPCs). Unfortunately, the efficiency of remyelination declines with progressive aging partially due to the depletion of OPCs following chronic or repeated demyelination. However, to our knowledge, so far there is no drug which enhances proliferation of OPCs, and it is unknown whether inhibiting RIPK1 activity directly affect OPCs, the central player of remyelination. Using TNFα induced RIPK1-dependent necroptosis in Jurkat FADD−/− cells as a cell death assay, we screened from 2112 FDA-approved drugs and the drug candidates of new RIPK1 inhibitors selected by ourselves, and identified ZJU-37, a small molecule modified by introducing an amide bond to Nec-1s, is a new RIPK1 kinase inhibitor with higher potency than Nec-1s which has the best reported potency. We unveil in addition to protecting myelin from demyelination and axons from degeneration, ZJU-37 exhibits a new role on promoting proliferation of OPCs and enhancing remyelination by inhibiting RIPK1 kinase activity with higher potency than Nec-1s. Mechanistically, ZJU-37 promotes proliferation of OPCs by enhancing the transcription of platelet derived growth factor receptor alpha via NF-κB pathway. This work identifies ZJU-37 as a new drug candidate which enhances remyelination by promoting proliferation of OPCs, paving the way for a potential drug to enhance myelin repair.

Cloperastine hydrochloride, a piperidine derivative, is a drug substance with a central antitussive effect and widely used in cough treatment; and its impurities have not been reported. Herein we isolated and identified five impurities (named as impurity A, B, C, D and E) in cloperastine hydrochloride bulk drug and developed a quantitative HPLC method. First, impurity A, B, C were enriched by ODS column chromatography and isolated by semi-preparative HPLC, at the same time, impurity D was purified by ODS column chromatography. Then, impurity E was enriched by strong acid degradation and purified by semi-preparative HPLC. At last, their structures were characterized by a variety of spectral data (MS, 1H NMR, 13C NMR, HSQC, HMBC and 1H-1H COSY). Impurity A was confirmed as 1-[2-(diphenylmethoxy)ethyl]piperidine, which having one less chloro-substituent compared with cloperastine. Impurity B was confirmed as 1-[2-[(2-chlorophenyl)(phenyl)methoxy]ethyl]piperidine, which was the isomer of cloperastine with 2-chloro-substituent. Impurity C was confirmed as 1-[2-[(3-chlorophenyl)(phenyl)methoxy]ethyl]piperidine, which was the isomer of cloperastine with 3-chloro-substituent. Impurity D was confirmed as (4-chlorophenyl)(phenyl)methanone, which was the raw material for the synthesis of cloperastine. Impurity E was confirmed as (4-chlorophenyl)(phenyl)methanol, which was an intermediate in the synthesis of cloperastine, and it was also a hydrolysate of cloperastine. Finally, the developed method was validated in terms of specificity, linearity, sensitivity, precision and accuracy.

Programmed cell death (PCD) plays a critical role in the development of plant pigment glands, while H2O2, which is a kind of reactive oxygen species (ROS) produced by the aerobic metabolism of cells, acts as an important signal in this process. Here, we investigated the temporal and spatial dynamics of accumulated H2O2 in pigment glands of Gossypium hirsutum L. with 3,3-diaminobenzidine (DAB) staining, 2',7'-dichlorodihydrofluorescein diacetate (DCFH2)-DA fluorescent labeling and CeCl3 cytochemical localization techniques. The results showed that the pigment glands of G. hirsutum could generate H2O2, and the amount and localization of H2O2 varied at different developmental stages. At the early developmental stage, a small amount of H2O2 accumulated in the vacuole membrane of pigment gland cells. At the intermediate stage, a large number of H2O2 appeared in the vacuole membrane, while cell walls started to accumulate a small amount of H2O2. When pigment gland cell degraded, H2O2 mainly accumulated on the chloroplast envelope membrane of inner sheath cells. With the degradation of the sheath cells, H2O2 was detected in cell wall and the membrane of secretory vesicles which contains the preliminary contents of pigment gland. With the pigment glands completely maturation, H2O2 would disappeared. The accumulation sites of H2O2 are consistent with the process of PCD of individual gland cells, which started from the degradation of intracellular membrane and ended with the degradation of cell walls. Thus H2O2 probably plays an important role in the development of pigment glands. In addition, the development of pigment glands and the generation of H2O2 are not associated with the light, and no H2O2 was detected in the secretions of pigment glands.

For the problem of pellet density control in the fish feed extrusion forming process, the influence of extrusion speed, the depth of die hole and the interaction of the two factors on feed pellet density was studied by experiment method. The study results own good application value because as theoretical basis they can be used to determine the extrusion scheme and optimize the granulator structural parameters.

To facilitate gas exchange, some plants produce specialized air cavities called aerenchyma. To determine how the aerenchyma is formed, we conducted serial experimental observations and tests. Here we provide evidence that aerenchyma is formed in Typha angustifolia leaves through cell lysis in which programmed cell death (PCD) is involved. We first observed by light microscopy that aerenchyma was formed by degradation of some specialized cells, the designated PCD-susceptible cells. Consistent with this observation, a TUNEL assay displayed the typical PCD features of in situ DNA fragmentation. The biomarkers of PCD were further revealed by gel electrophoresis. Using electron microscopy, we further observed that the PCD-susceptible cells underwent several organized changes that are typically associated with PCD, including emergence of vesicles, rupture of tonoplast, and degradation of cytoplasm, organelles, and cell walls. Additionally, we observed that calcium oxalate crystals appeared at the early cavity formation phase and disappeared at the late cavity formation phase during aerenchyma formation. Taken together, our results suggest that PCD plays a critical role in the development of lysigenous aerenchyma in T. angustifolia leaves.

To the Editor: The syndrome of mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) is one of the most frequently occurring mitochondrial disorders. Dandy–Walker malformation (DWM) is a rare posterior fossa malformation. We report a 21-year-old male with DWM and MELAS syndrome. This report focuses on a 21-year-old Chinese male who is the only child of nonconsanguineous parents. His family history was unremarkable. Developmental milestones were achieved at the appropriate ages. The patient presented with his fourth stroke-like event within a 2-year period. The primary clinical manifestations were aphasia, recurrent headache, muscular weakness, cortical blindness, and seizures. Neurological examination showed anomic aphasia, right visual field deficits, left hemiparesis (muscle power was 4/5), gait ataxia, and cognitive impairment (mini-mental state examination score of 16). The cerebrospinal fluid examination was unremarkable. At 8 h after the event, the lactic acid levels were 200 mg/L. A significant increase in lactic acid levels in the serum was observed during the stroke-like event. They increased to 700–1200 mg/L during the event and decreased to 250 mg/L afterward. Several magnetic resonance imaging (MRI) results revealed infarcts in the bilateral temporal lobes and the parietal and occipital lobes, which were inconsistent with any vascular distribution [Figure 1]. Meanwhile, there was demonstrated hypoplasia of the cerebellar vermis and cystic dilatation of an enlarged fourth ventricle, which are consistent with a diagnosis of DWM [Figure 2]. Repeated cerebrovascular disease tests were negative for stenosis and abnormalities. Figure 1 Magnetic resonance imaging results (diffusion weighted imaging) from the patient suffered four “stroke-like” accidents showing lesions at (a) left temporal lobe, (b) left temporal and occipital lobe, (c) right temporal lobe, (d) right ... Figure 2 Axial T1-weighted brain magnetic resonance imaging results. It demonstrates the (a) hypoplasia of cerebellum and enlarged fourth ventricle and (b) hydrocephalus findings of characteristics of Dandy–Walker malformation. During his admission in May 2014, polymerase chain reaction was used to sequence the patient's DNA. An AG mutation (A3243G) was found in the tRNA-Leu gene of the mitochondrial DNA, confirming MELAS syndrome. Therefore, he was diagnosed with MELAS syndrome and DWM. The last stroke-like period was treated with coenzyme Q10 (CoQ10, 100 mg, 3 times/day), butylphthalide soft capsules (0.2 g, 3 times/day), and levetiracetam tablets (1000 mg, 2 times/day). At 6-month follow-up, the symptoms of aphasia, headache, cortical blindness, and seizures were disappeared, but his cognitive impairment and left hemiparesis remained unaltered. Unfortunately, we were unable to perform follow-up brain MRI. DWM is characterized by hypoplasia or agenesis of the cerebellar vermis, involving the cortex and deep cerebellar nuclei, enlargement of the fourth ventricle in continuity with a posterior fossa cyst. It has been shown to be associated with multiple congenital anomalies or other diseases including down syndrome, Wisconsin syndrome, neurocutaneous melanosis, and schizophrenia.[1,2,3,4] However, to the best of our knowledge, there are few reports of a DWM diagnosis associated with mitochondrial diseases. MELAS syndrome is one of the most frequently occurring mitochondrial disorders and is most commonly caused by an A-to-G transition mutation at the 3243 position of the mitochondrial genome. However, mutations in the nuclear DNA may also contribute to this disorder. Many findings suggest that DWM is primarily due to a nuclear genome alteration. Unfortunately, we were unable to perform autosomal DNA tests on the patient because of cost. It is unclear that whether the coincidence of MELAS and DWM is coincidental or causal, further researches are needed to elucidate this possible association. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.