Search

Objective This study was designed to observe the effect of electroacupuncture at Hegǔ (合谷LI4), or Houxī (后溪SI3) or Waiguān (外关TE5) acupoints on the function of the brain regions of a healthy human, and to explore the neural information mechanism of a specific connection between LI4 and the facial-oral area from the point of view of the brain function connection network. A further objective was to enrich knowledge of the specific connection between the body surface and the meridian route, and the specificity of acupoint effects. Methods A total of 30 healthy volunteers were randomly assigned to LI4, SI3, and TE5 groups. The members of each group were stimulated with electroacupuncture, and their heads were scanned using fMRI. DPARSFA 2.4 and REST 1.8 software were used for data preprocessing and statistical analysis. The paired t-test was used within group and the double sample t-test was used for two-group comparisons. Results In healthy people, left LI4 with electroacupuncture mainly caused a decrease of the functional connection of the right orofacial motor area of the brain, which remained decreased after removing the needle. When LI4 was compared with SI3 and TE5, LI4 caused a more significant decline in the functional connection of the right side of the brain during acupuncture. Conclusions Acupuncture at LI4 has a significant effect on the function of the face- and mouth-related areas in the brain, and there is a continuous effect. It is suggested that LI4 and the face and mouth have a specific relationship in the brain, which is most obvious during acupuncture.

Background Mutations in the SPAST gene are the most frequent cause of hereditary spastic paraplegia (HSP). We aim to extend the mutation spectrum of spastic paraplegia 4 (SPG4) and carried out experiment in vitro to explore the influence of the SPAST gene mutation on the function of corresponding protein. Methods Whole-exome sequencing (WES) combined with multiplex ligation-dependent probe amplification (MLPA) were performed in a cohort of 150 patients clinically diagnosed with HSP. We focus on screening for mutations in SPAST gene and carrying out functional experiments to assess the effects of the novel variants. Results A total of 34 different mutations in the SPAST gene were identified, of which 10 were novel, including 1 missense (c.1479T > A), 1 nonsense (c.766G > T), 3 splicing (c.1413 + 1_1413+4delGTAA, c.1729-1G > A and c.1536+2T > G) and 5 frameshift mutations (c.1094delC, c.885dupA, c.517_518delAG, c.280delG and c.908dupC). For 7 novel non-splicing mutations, functional study showed that accumulated M1 spastin colcocalized with microtubules which was different from a uniformly diffused M87 spastin. While an impairment in severing activity was observed in both mutant M1 and mutant M87, except for c.280delG. All 3 novel splicing variants w ere predicted to affect splicing by using bioinformatic programs. However, only c.1536+2T > G had no influence on splice site in vitro, which conflicts with the in-silico analysis. Conclusion We genetically diagnosed 40 SPG4 patients. All the novel non-splicing mutations except for c.280delG were certified to exert an effect on the microtubule-severing and all the novel splicing mutations other than c.1536+2T > G would cause abnormal splicing of the spastin.

Exercise can prevent osteoporosis and improve immune function, but the mechanism remains unclear. Here, we show that exercise promotes reticulocalbin-2 secretion from the bone marrow macrophages to initiate bone marrow fat lipolysis. Given the crucial role of lipolysis in exercise-stimulated osteogenesis and lymphopoiesis, these findings suggest that reticulocalbin-2 is a pivotal regulator of a local adipose-osteogenic/immune axis. Mechanistically, reticulocalbin-2 binds to a functional receptor complex, which is composed of neuronilin-2 and integrin beta-1, to activate a cAMP-PKA signaling pathway that mobilizes bone marrow fat via lipolysis to fuel the differentiation and function of mesenchymal and hematopoietic stem cells. Notably, the administration of recombinant reticulocalbin-2 in tail-suspended and old mice remarkably decreases bone marrow fat accumulation and promotes osteogenesis and lymphopoiesis. These findings identify reticulocalbin-2 as a novel mechanosensitive lipolytic factor in maintaining energy homeostasis in bone resident cells, and it provides a promising target for skeletal and immune health.

To observe the effects of moxibustion on "Shenshu" and "Zusanli" on macrophage polarization and IL-4/STAT6 signaling pathway in rats with rheumatoid arthritis (RA). To further explore the possible anti-inflammatory mechanism of moxibustion in the treatment of RA.The rats' right hind paws were injected with freund's complete adjuvant (FCA) to establish the model of RA. Seven days after the injection of FCA, moxibustion therapy was performed on the acupoints of Shenshu (BL23) and Zusanli (ST36) once a day for three weeks. The researchers measured the thickness of the foot pad. ELISA and Histological Analysis were performed to observe the anti-inflammatory effect of moxibustion. Then researchers detected the expression of macrophage phenotype and the expression of IL-4/STAT6 signaling pathway related molecules.It was observed that after the injection of FCA, the rats' feet showed obvious symptoms of redness and swelling. But the symptoms were significantly improved when moxibustion was employed. The study found lower IL-23 and higher IL-4 level in the serum of FCA-injected rats after moxibustion treatment. HE staining showed that the synovium of the RA group was hyperemia and edema, with a large number of inflammatory cells infiltration and vascular dilatation. In the moxibustion group, the degree of synovial hyperemia and edema was improved, and the infiltration of inflammatory cells and vascular dilation were reduced. The study also found that there wer differences among the expressions of macrophage phenotypes in RA, and this was shown by the high expression of CD86 and low expression of CD206. However, the polarization of macrophages in the moxibustion group changed, and that was manifested by enhanced M2-polarized Mφs and inhibited M1-polarized Mφs. Meanwhile, moxibustion suppressed the activation of JAK1, JAK3 and STAT6 in the IL-4/STAT6 signaling pathway, which contributed to the polarization of M2 .The results demonstrate that moxibustion not only suppresses the polarization of M1, but also promotes the polarization of M1. The anti-inflammatory effect of moxibustion may be related to the regulation of macrophage polarization through IL-4/STAT6 signaling pathway.

In this study, a community-scale in-situ rapid biological reduction (IRBR) system was applied to achieve the rapid disposal and resource recovery of food waste (FW). A total of 5263 kg FW was processed in the 35 days of stably operation, during which 84.37% total mass reduction and 43.30% volatile solid removal were achieved, and the odor had been effectively controlled. Microbial sequencing results showed that aerobic and facultative thermophilic bacteria were major bacterial community, and vigorous metabolism of both carbohydrate and amino acid were maintained during the IRBR process. The final products have the potential to be recycled as organic fertilizers or bio-solid fuel to realize resource recovery. The results of economic analysis showed that the IRBR system had lower FW disposal costs due to the high automation. These results suggested that the IRBR system was an environmentally friendly, economical and practical method for the FW rapid treatment.

Objective To unravel if there was muscular ion channel dysfunction in paroxysmal kinesigenic dyskinesia (PKD) patients using the exercises tests (ET). Methods Sixty PKD patients including 28 PRRT2 mutations carriers were enrolled in this study, as well as 19 hypokalaemic periodic paralysis (HypoPP) patients as the positive controls and 45 healthy subjects as the negative controls. ET including long exercise test (LET) and short exercise test (SET) was performed in the corresponding subjects. Results In the LET, both the overall PKD patients and HypoPP patients had greater CMAP amplitude and area increments during exercise than healthy controls. At most 25% of PKD patients were identified from the normality with greater amplitude increment than the area. On the contrary, 50% of HypoPP patients were differentiated with greater area increment than the amplitude. More percentage of PRRT2− patients than PRRT2+ patients had abnormal average amplitude increment. Unexpectedly, five PKD patients had abnormal maximum CMAP amplitude decrements after exercise in the LET, and one had abnormal maximum immediate amplitude decrement in the SET. Conclusions Distinct ET manifestations were found in PKD patients compared to normal controls and HypoPP patients. Significance Abnormal muscle membrane excitability might be involved in the mechanisms responsible for PKD.

Background Standardized mortality ratio (SMR) is the most frequently used index in Parkinson's disease (PD) survival survey. However, there is little SMR data in PD from China. Objective To examine the outcome, including overall and cause-specific mortality, of PD patients subsequent to 10 years of surveillance in Shanghai, China. This is an extension study of our previous investigation on mortality. Methods One hundred fifty-seven PD patients recruited from the movement disorder clinic of Rui Jin Hospital in 2006 were followed up until December 31, 2016 or death, representing a follow-up period of up to 10 years. Overall and cause-specific standardized mortality ratios (SMR) were calculated, and predictors for survival at disease onset were estimated. Results Thirty one patients had died by December 31, 2016, and the SMR at 10 years of follow-up was 0.87 (0.59–1.25). The primary direct cause of death was respiratory disease (SMR = 3.52, 95% CI 1.98–5.78). Employing Cox's proportional hazard modeling, postural instability gait disorder (PIGD) type and older age at onset predicted poor survival in this cohort. Conclusions This finding confirms the similar survival of patients with PD to the control population in the post-levodopa era. PIGD type and older age at onset had a negative impact on survival.

β-Alanine is the only naturally occurring β-amino acid, widely used in the fine chemical and pharmaceutical fields. In this study, metabolic design strategies were attempted in Escherichia coli W3110 for enhancing β-alanine biosynthesis. Specifically, heterologous L-aspartate-α-decarboxylase was used, the aspartate kinase I and III involved in competitive pathways were down-regulated, the β-alanine uptake system was disrupted, the phosphoenolpyruvate carboxylase was overexpressed, and the isocitrate lyase repressor repressing glyoxylate cycle shunt was delete, the glucose uptake system was modified, and the regeneration of amino donor was up-regulated. On this basis, a plasmid harboring the heterologous panD and aspB was constructed. The resultant strain ALA17/pTrc99a-panDBS-aspBCG could yield 4.20 g/L β-alanine in shake flask and 43.94 g/L β-alanine (a yield of 0.20 g/g glucose) in 5-L bioreactor via fed-batch cultivation. These modification strategies were proved effective and the constructed β-alanine producer was a promising microbial cell factory for industrial production of β-alanine.

As the key precursor of coenzyme A synthesis in vivo, D-pantothenic acid plays an important role in maintaining biological function, which is widely applied in the food, pharmaceutical, and cosmetic industries. At present, it was mainly produced by chemical methods, with serious environmental pollution, therefore, it is urgent to develop an economical, practical, and environmentally friendly biological fermentation method based on microbial chassis cells. Herein, based on our previously developed D-pantothenic acid producing strains, we obtained higher yielding D-pantothenic acid producing strains by systematic metabolic engineering. First, according to the results of CRISPRi experiments, lpd were overexpressed, disrupted the non-PTS (non-phosphoenolpyruvate-pyruvate transport system) as well as enhanced the PTS (phosphoenolpyruvate-pyruvate transport system) allowing precursor accumulation. Subsequently, based on the analysis of metabolic intermediates, the pyruvate bypass pathway was blocked as well as the (R)-pantothenic acid pathway was further enhanced, increasing the titer of D-pantothenic acid to 4.60 g/L. Finally, the organic acid and branched-chain amino acid synthesis pathways were blocked, and in order to accelerate the synthesis of acetolactate and the output of D-pantothenic acid, heterologous acetolactate synthase and pantothenate transfer protein were introduced, which significantly increased the yield of D-pantothenic acid, reach to 6.33 g/L. The final strain in a 5 L bioreactor produced 32.32 g/L D-pantothenic acid with a productivity of 2.33 g/L/h and the high-yielding strain provides an effective platform for biological fermentation to produce D-pantothenic acid.

A novel anthrancene-dopamine thioether L compound was designed as fluorescent probe for detecting Hg2+ in living cells sample. L exhibits a good sensitive and selective recognition towards Hg2+ ions in the presence of other important relevant metal ions and amino acids in HEPES solution. The addition of Hg2+ causes a marked enhancement in the fluorescence emission intensity with the detection limit as low as 1.1×10-6M, combining with obvious colormetric change from colorless to pale brown. Mechanistic studies show that catechol group and sulfur atom in L all participate in the coordination with Hg2+, though catechol group contributes mainly to chelation-enhanced fluorescence enhancement and sulfur atom to selectivity. Furthermore, L demonstrates good cell permeability and compatibility for sensitive fluorescent detection of Hg2+ in HepG2 cells. This present probe will have broad applications in biological imaging.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1), also known as distal spinal muscular atrophy 1 (DSMA1) or distal hereditary motor neuropathies type 6 (dHMN6), is a rare autosomal recessive motor neuron disorder that affects infants and is characterized by diaphragmatic palsy, distal muscular weakness and muscle atrophy. The disease is caused by mutations in the gene encoding immunoglobulinm-binding protein 2 (IGHMBP2). We present a female child with novel compound heterozygous mutations in IGHMBP2 gene c.344C>T (p.115T>M) and c.1737C>A (p.579F>L), displaying distal limbs weakness and atrophy without signs of diaphragmatic palsy or respiratory insufficiency. We review 20 reported SMARD1 cases that have no respiratory involvement or have late onsets. We propose that IGHMBP2 gene mutations are characterized by significant phenotypic heterogeneity. Diaphragmatic palsy and respiratory distress may be absent and SMARD1 should be considered in infantile with the onset of peripheral neuropathies.

A new enzyme-catalyzed asymmetric construction of chiral tertiary alcohols via asymmetric aldol reactions between β,γ-unsaturated α-keto esters and ketones was reported. Proteinase from Aspergillus melleus (AMP) was used as a sustainable biocatalyst. The best results can be obtained with yields of up to 90%, diastereoselectives of up to 93:7 dr, and enantioselectivities of up to 70% ee. This work not only expands the application of enzymatic promiscuity, but also provides more examples for constructing chiral tertiary alcohols.

Transcranial sonography can display structural alterations in the substantia nigra (SN) of patients with Parkinson's disease (PD), and is considered to be a potential useful tool for the diagnosis of PD. The aim of this study was to assess the correlation between SN echogenicity and clinical features in Chinese patients with PD.A total of 420 subjects including 290 patients with PD and 130 controls were recruited from the neurological clinic or the community. Transcranial sonographic evaluations of the SN were performed in all subjects, and motor and non-motor symptoms were thoroughly assessed by a series of rating scales in PD patients.Two hundred and one patients were successfully assessed by transcranial sonography. SN hyperechogenicity was found to be associated with male sex (p = 0.004), higher scores on the Unified Parkinson's Disease Rating Scale (UPDRS) part II (p = 0.001) and autonomic symptoms scores (p = 0.003). Moreover, regression analysis revealed that UPDRS part II scores (odds ratio = 1.141, p0.001) and gender (odds ratio = 2.409, p = 0.007) could be the independent predictors for SN hyperechogenicity; in addition, among all items of UPDRS part II, speech, dressing, hygiene, and turning in bed and adjusting bed clothes significantly correlated with SN hyperechogenicity.This is the first report suggesting the correlation between SN echogenicity and UPDRS part II, and we conclude that increased SN echogenicity might reflect more severe disease disability or poorer medical response.

Introductions Transcranial sonography (TCS) of the substantia nigra is a new and promising method to diagnose Parkinson's disease (PD) but its effectiveness is controversial. Methods All 55 PD patients involved in the study underwent single photon emission computed tomography (SPECT) imaging using the labeled dopamine transporter radiotracer 99mTc-TRODAT-1 to assess nigrostriatal dopaminergic function. The echogenicity of the substantia nigra was measured by TCS in all patients who received DAT-SPECT scanning. Finally, statistical analysis was carried out to determine the diagnostic accuracy of TCS as well as its correlation with 99mTc-TRODAT-1 SPECT, its positive predictive value (PPV), and negative predictive value (NPV). Results Contralateral striatal 99mTc-TRODAT-1 uptake was significantly reduced compared to ipsilateral striatal uptake, and had a negative correlation with UPDRS-Ⅲ(r = −0.334, p = 0.013), disease duration (r = −0.393, p = 0.003) and H–Y stage (r = −0.330, p = 0.014). After TCS measurement, the contralateral SN echogenic area was similar to the ipsilateral SN echogenic area (27.77 ± 13.19 vs 25.98 ± 11.94 mm2, p = 0.402, n = 24). No correlation was identified between TCS and UPDRS-Ⅲ (r = 0.383, p = 0.065), disease duration (r = 0.371, p = 0.075) or H–Y stage (r = 0.259, p = 0.222). The sensitivity and specificity of SN TCS for the diagnosis of PD were calculated as 64.70% and 60% according to DAT-SPECT, respectively, while the positive predictive value and negative predictive value was calculated as 91.67% and 20%, respectively. Conclusions Compared to DAT-SPECT, TCS is a non-radioactive and convenient procedure to perform. In our investigation, TCS had no correlation with DAT-SPECT. However, the high positive predictive value of TCS highlights its possible utility as a routine diagnostic test.

Accumulating evidence suggests that adiponectin plays an important role in the genesis of obesity and insulin resistance. Although it has been shown that glucocortocoids (GC) inhibit adiponectin expression in vitro, there exist discrepant results in vivo. In this study, we observe the effect of GC on the serum adiponectin level and adiponectin expression in white adipose tissue (WAT) in male SD rats.An obese rat model was made by a high-fat diet. Both non-obese and obese rats were randomly divided into normal saline (intraperitoneal injection with normal saline 0.2ml/100gday for 20 days, NS), a low dose GC group (intraperitoneal injection with hydrocortisone sodium succinate 5mg/kgday for 20 days, LDG) and a high dose GC group, respectively (intraperitoneal injection with hydrocortisone sodium succinate 15mg/kgday for 20 days, HDG). Serum adiponectin levels were detected by ELISA and the adiponectin mRNA level was assayed by Northern blot.The serum adiponectin level significantly decreased after 80 days of the high-fat diet (P0.05), while it was not decreased after 80 days of the chow diet (P0.05). The serum adioponectin levels in both the non-obese and obese rats were significantly decreased after a 20-day GC injection period (P0.01). The adiponectin mRNA levels in epididymal fat after high dose GC injection, in both non-obese and obese rats were also decreased (P0.001).A high-fat diet decreased serum adiponectin levels in the rat. GC decreased serum adiponectin levels, and this might be due to inhibited adiponectin mRNA expression in WAT. High-fat diet and GC have a synergistic effect on inhibiting adiponectin expression in rats.

This study was conducted to evaluate the prevalence of malnutrition among patients with Parkinson's disease (PD) and determine the associations between malnutrition and non-motor symptoms (NMS).We conducted a cross-sectional assessment of 117 consecutive outpatients with PD and their respective caregivers. The participants were interviewed and assessed using various scales, including the Mini Nutritional Assessment (MNA), Non-Motor Symptoms questionnaire for Parkinson's disease (NMS quest), Mini-mental State Examination (MMSE), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Geriatric Depression Scale (GDS), and Hamilton Anxiety Scale (HAMA). We also investigated the socio-demographic characteristics of the subjects.The prevalence of malnutrition (MNA score17) was 1.71%, and 19.66% patients were at risk of malnutrition (17or= MNA scoreor= 23.5). Poor nutrition (malnutrition and at risk of malnutrition) was associated with some of the NMS including the constipation, vomiting, loss of interest, inability to concentrate and sadness, and high scores in PSQI, GDS, and HAMA. Constipation (OR, 6.646; 95% CI, 1.561-28,300; P = 0.010) and GDS scores (OR, 1.166; 95% CI, 1.042-1.304; P = 0.007) were considered to be the 2 most important predictors of nutritional impairment.Nearly 22% of PD patients were malnourished or at the risk of malnutrition and the negative association between NMSs and nutritional care needs to be determined by further studies.

Pituitary adenylate cyclase activating polypeptide (PACAP) exhibits a protective effect against neural injury in vitro and in vivo. However, it has not been reported whether peripheral intravenous administration of PACAP could confer benefits in animal models of Parkinson's disease (PD). Furthermore, the underlying molecular mechanisms responsible for these effects are poorly understood. In the present experiments, we determined the effects and mechanism of action of intravenously administered PACAP27 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Our results indicate that intravenous injection of PACAP27 offers neuroprotective effects in the MPTP-induced PD mouse model which may not be directly associated with the expression levels of the monoamine transporters. However, this effect may be correlated with its ability to selectively regulate not only K(ATP) subunits, but D2 receptors in the striatum. Our findings suggest that the benefit of PACAP may accompany with changes not only in dopaminergic neurotransmission, but also in cholinergic neurotransmission that are relatively associated with the K(ATP) subunits and D2 receptors in the striatum.

Fruit aroma of Guoqing 1, Miyagawa Wase, and Owari from three different Satsuma mandarin varieties were investigated by headspace solid phase microextraction (HS-SPME) combined with GC-MS. The results showed that there were 73, 71, and 66 aroma components in the three varieties, and the total contents were 584.67, 505.29, and 494.63 μg g^(-1), respectively. Total 29 constituents were common in the three varieties. It was also found that Guoqing 1, Miyagawa Wase, and Owari had 12, 5, and 2 unique components, respectively. The key aroma components were limonene, linalool, γ-terpinene, β-myrcene, α-pinene, and octanal in the three fruits. Guoqing 1 contained more key aroma compounds than Miyagawa Wase and Owari.

A novel HPLC-UV method with pre-column derivatization by using 2-mercaptoethanol was established for determination of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]-ethane (BBSKE) in dog plasma. The derivatives were identified by mass spectrometry. The method had a good linear range of 0.05-2 microg/ml (r(2)=0.9995). The lower limit of quantification (LOQ) was 0.05 microg/ml. The precision and accuracy were less than 7%. After dosing of BBSKE (30 mg/kg, p.o. and 0.79 mg/kg, i.v.) in dogs, AUC(0-t) were 5.72+/-2.42 and 1.35+/-0.41 microg h/ml; t(1/2) were 4.6+/-2.1 and 1.7+/-0.6h, respectively. The method was successfully applied to the pharmacokinetic study in dogs.

ATP13A2 (PARK9) mutations are related to Kufor-Rakeb syndrome (KRS). We performed genetic analysis of the Ala746Thr variant in an independent cohort of the patients with PD and healthy controls from mainland China. The Ala746Thr variant was present in 1/532 (0.19%) of PD compared with 1/480 (0.21%) of healthy controls (odds ratio=0.90, 95% CI 0.06, 14.39, P=1.00). The two subjects carried the heterozygous genotype. Subset analysis in the group/=50 years of age revealed a prevalence of 0.7% in PD compared with 0% in healthy controls and in the group50 years of age showed 0% in PD versus 0.3% in healthy controls. We did not observe a significant association between Ala746Thr and Parkinson's disease in Han Chinese population, even after stratification by age at onset. The results suggested that Ala746Thr variant was not a major susceptible factor for PD in Han Chinese people.

A new dicoumarin, named as dimeresculetin (1), together with another dicoumarin, euphorbetin (2) and esculetin (3) were isolated from the ethyl acetate extract of the dried whole plants of Viola yedoensis Makino. The structure of 1 was elucidated as 7-hydroxy-6-[(6,7-dihydroxy-2-oxo-2H-1-benzopyran-5-yl)oxy]-2H-1-benzopyran-2-one on the basis of extensive NMR, as well as the other spectral analysis. Compounds 1-3 exhibited anticoagulant activities with respect to activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT).

• We identified one de novo novel mutation in KCNJ2 gene in a Chinese patient with Andersen–Tawil syndrome.