Endocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation.

Glycolysis is a fundamental cellular process, yet its regulatory mechanisms remain incompletely understood. Here, we show that a subset of glucose transporter 1 (GLUT1/SLC2A1) co-endocytoses with platelet-derived growth factor (PDGF) receptor (PDGFR) upon PDGF-stimulation. Furthermore, multiple glycolytic enzymes localize to these endocytosed PDGFR/GLUT1-containing vesicles adjacent to mitochondria. Contrary to current models, which emphasize the importance of glucose transporters on the cell surface, we find that PDGF-stimulated glucose uptake depends on receptor/transporter endocytosis. Our results suggest that growth factors generate glucose-loaded endocytic vesicles that deliver glucose to the glycolytic machinery in proximity to mitochondria, and argue for a new layer of regulation for glycolytic control governed by cellular membrane dynamics.

Debugging and consolidating multiple synthetic chromosomes reveals combinatorial genetic interactions.

The Sc2.0 project is building a eukaryotic synthetic genome from scratch. A major milestone has been achieved with all individual Sc2.0 chromosomes assembled. Here, we describe the consolidation of multiple synthetic chromosomes using advanced endoreduplication intercrossing with tRNA expression cassettes to generate a strain with 6.5 synthetic chromosomes. The 3D chromosome organization and transcript isoform profiles were evaluated using Hi-C and long-read direct RNA sequencing. We developed CRISPR Directed Biallelic URA3-assisted Genome Scan, or "CRISPR D-BUGS," to map phenotypic variants caused by specific designer modifications, known as "bugs." We first fine-mapped a bug in synthetic chromosome II (synII) and then discovered a combinatorial interaction associated with synIII and synX, revealing an unexpected genetic interaction that links transcriptional regulation, inositol metabolism, and tRNASerCGA abundance. Finally, to expedite consolidation, we employed chromosome substitution to incorporate the largest chromosome (synIV), thereby consolidating >50% of the Sc2.0 genome in one strain.

3D reconstructions of parasite development and the intracellular niche of the microsporidian pathogen Encephalitozoon intestinalis.

Microsporidia are an early-diverging group of fungal pathogens with a wide host range. Several microsporidian species cause opportunistic infections in humans that can be fatal. As obligate intracellular parasites with highly reduced genomes, microsporidia are dependent on host metabolites for successful replication and development. Our knowledge of microsporidian intracellular development remains rudimentary, and our understanding of the intracellular niche occupied by microsporidia has relied on 2D TEM images and light microscopy. Here, we use serial block-face scanning electron microscopy (SBF-SEM) to capture 3D snapshots of the human-infecting species, Encephalitozoon intestinalis, within host cells. We track E. intestinalis development through its life cycle, which allows us to propose a model for how its infection organelle, the polar tube, is assembled de novo in developing spores. 3D reconstructions of parasite-infected cells provide insights into the physical interactions between host cell organelles and parasitophorous vacuoles, which contain the developing parasites. The host cell mitochondrial network is substantially remodeled during E. intestinalis infection, leading to mitochondrial fragmentation. SBF-SEM analysis shows changes in mitochondrial morphology in infected cells, and live-cell imaging provides insights into mitochondrial dynamics during infection. Our data provide insights into parasite development, polar tube assembly, and microsporidia-induced host mitochondria remodeling.

Electroacupuncture improving obesity-induced insulin resistance via regulating intestinal SIRT1/TLR4 signaling pathway. / ç”µé’ˆè°ƒæŽ§å°è‚ æ²‰é»˜ä¿¡æ¯è°ƒèŠ‚å› å­1/Tollæ ·å—ä½“4ç‚Žæ€§é€šè·¯æ”¹å–„è‚¥èƒ–å¤§é¼ èƒ°å²›ç´ æŠµæŠ—çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) in obese rats with insulin resistance (IR) through regulating intestinal silent information regulator 1 (SIRT1)/Toll-like receptor 4 (TLR4) signaling pathway, so as to explore the underlying mechanism of EA in improving obesity-induced IR. METHODS: A total of 40 Wistar rats were randomly divided into 4 groups, i.e. normal group, model group, EA group and EA combined with inhibitor group, with 10 rats in each group. The obesity-induced IR model was induced by feeding high-fat diet for 8 weeks. EA (2 Hz, 1mA) was applied at "Zhongwan"(CV12), "Guanyuan"(CV4), "Zusanli"(ST36) and "Fenglong" (ST40) for 10 min, 3 times a week for 8 weeks in both EA and EA combined with inhibitor groups. Sirtinol, an inhibitor of SIRT1 was injected into the tail vein (1 mg/kg), 3 times a week for 8 weeks in EA combined with inhibitor group. The body weight, glucose infusion rate (GIR) of rats in each group were recorded. The contents of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and lipopolysaccharide (LPS) were detected by ELISA. Mucosal morphological changes in the small intestine was observed by HE staining and was graded using Chiu's score. The protein relative expression levels of SIRT1 and TLR4 and the co-labeling of SIRT1 with TLR4 in the small intestine was detected by Western blot and double immunofluorescence staining, separately. RESULTS: Compared with the normal group, the body weight, serum contents of CRP, TNF-α, IL-6, LPS, Chiu's score, TLR4 protein relative expression level and percentage of TLR4 positive expression area were increased (P<0.01, P<0.05), while the GIR, SIRT1 protein expression, percentage of SIRT1 positive expression area and SIRT1/TLR4 were decreased (P<0.01) in the model group. The pathological injury of small intestine mucosa was severe, accompanied with inflammatory cell infiltration in the model group. Following interventions, the body weight, serum contents of CRP, TNF-α and LPS, Chiu's score, TLR4 protein relative expression level and percentage of TLR4 positive expression area were decreased(P<0.01, P<0.05), and the GIR was increased (P<0.01), the pathological injury and inflammatory cell infiltration of small intestine mucosa were reduced in both EA and EA combined with inhibitor groups in contrast to the model group. Compared with the model group, the serum IL-6 content was significantly decreased (P<0.01), and the SIRT1 protein relative expression level and percentage of positive expression area, SIRT1/TLR4 were increased (P<0.01, P<0.05) in the EA group. Compared with the EA group, EA combined with inhibitor group showed the body weight, serum CRP, IL-6, LPS, Chiu's score, TLR4 protein relative expression level and TLR4 positive expression area were increased (P<0.01, P<0.05), and the GIR level , SIRT1 relative expression level, SIRT1/TLR4 ratio were decreased (P<0.05, P<0.01). CONCLUSIONS: EA can reduce the body weight and ameliorate peripheral insulin sensitivity in IR obese rats, which may be related with its function in regulating intestinal SIRT1/TLR4 signaling pathway to reduce inflammatory response.

A noncanonical function of SKP1 regulates the switch between autophagy and unconventional secretion.

Intracellular degradation of proteins and organelles by the autophagy-lysosome system is essential for cellular quality control and energy homeostasis. Besides degradation, endolysosomal organelles can fuse with the plasma membrane and contribute to unconventional secretion. Here, we identify a function for mammalian SKP1 in endolysosomes that is independent of its established role as an essential component of the family of SCF/CRL1 ubiquitin ligases. We found that, under nutrient-poor conditions, SKP1 is phosphorylated on Thr131, allowing its interaction with V1 subunits of the vacuolar ATPase (V-ATPase). This event, in turn, promotes V-ATPase assembly to acidify late endosomes and enhance endolysosomal degradation. Under nutrient-rich conditions, SUMOylation of phosphorylated SKP1 allows its binding to and dephosphorylation by the PPM1B phosphatase. Dephosphorylated SKP1 interacts with SEC22B to promote unconventional secretion of the content of less acidified hybrid endosomal/autophagic compartments. Collectively, our study implicates SKP1 phosphorylation as a switch between autophagy and unconventional secretion in a manner dependent on cellular nutrient status.

Bacterial contact induces polar plug disintegration to mediate whipworm egg hatching.

The bacterial microbiota promotes the life cycle of the intestine-dwelling whipworm Trichuris by mediating hatching of parasite eggs ingested by the mammalian host. Despite the enormous disease burden associated with Trichuris colonization, the mechanisms underlying this transkingdom interaction have been obscure. Here, we used a multiscale microscopy approach to define the structural events associated with bacteria-mediated hatching of eggs for the murine model parasite Trichuris muris. Through the combination of scanning electron microscopy (SEM) and serial block face SEM (SBFSEM), we visualized the outer surface morphology of the shell and generated 3D structures of the egg and larva during the hatching process. These images revealed that exposure to hatching-inducing bacteria catalyzed asymmetric degradation of the polar plugs prior to exit by the larva. Unrelated bacteria induced similar loss of electron density and dissolution of the structural integrity of the plugs. Egg hatching was most efficient when high densities of bacteria were bound to the poles. Consistent with the ability of taxonomically distant bacteria to induce hatching, additional results suggest chitinase released from larva within the eggs degrade the plugs from the inside instead of enzymes produced by bacteria in the external environment. These findings define at ultrastructure resolution the evolutionary adaptation of a parasite for the microbe-rich environment of the mammalian gut.

The REEP5/TRAM1 complex binds SARS-CoV-2 NSP3 and promotes virus replication.

IMPORTANCE: Generation of virus-host protein-protein interactions (PPIs) maps may provide clues to uncover SARS-CoV-2-hijacked cellular processes. However, these PPIs maps were created by expressing each viral protein singularly, which does not reflect the life situation in which certain viral proteins synergistically interact with host proteins. Our results reveal the host-viral protein-protein interactome of SARS-CoV-2 NSP3, NSP4, and NSP6 expressed individually or in combination. Furthermore, REEP5/TRAM1 complex interacts with NSP3 at ROs and promotes viral replication. The significance of our research is identifying virus-host interactions that may be targeted for therapeutic intervention.

Endocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation.

Glycolysis is a fundamental cellular process, yet its regulatory mechanisms remain incompletely understood. Here, we show that a subset of glucose transporter 1 (GLUT1/SLC2A1) co-endocytoses with platelet-derived growth factor (PDGF) receptor (PDGFR) upon PDGF-stimulation. Furthermore, multiple glycolytic enzymes localize to these endocytosed PDGFR/GLUT1-containing vesicles adjacent to mitochondria. Contrary to current models, which emphasize the importance of glucose transporters on the cell surface, we find that PDGF-stimulated glucose uptake depends on receptor/transporter endocytosis. Our results suggest that growth factors generate glucose-loaded endocytic vesicles that deliver glucose to the glycolytic machinery in proximity to mitochondria, and argue for a new layer of regulation for glycolytic control governed by cellular membrane dynamics.

Nanogold based protein localization enables subcellular visualization of cell junction protein by SBF-SEM.

Recent advances in volume electron microscopy (vEM) allow unprecedented visualization of the electron-dense structures of cells, tissues and model organisms at nanometric resolution in three dimensions (3D). Light-based microscopy has been widely used for specific localization of proteins; however, it is restricted by the diffraction limit of light, and lacks the ability to identify underlying structures. Here, we describe a protocol for ultrastructural detection, in three dimensions, of a protein (Connexin 43) expressed in the intercalated disc region of adult murine heart. Our protocol does not rest on the expression of genetically encoded proteins and it overcomes hurdles related to pre-embedding and immunolabeling, such as the penetration of the label and the preservation of the tissue. The pre-embedding volumetric immuno-electron microscopy (pre-embedding vIEM) protocol presented here combines several practical strategies to balance sample fixation with antigen and ultrastructural preservation, and penetration of labeling with blocking of non-specific antigen binding sites. The small 1.4 nm gold along with surrounded silver used as a detection marker buried in the sample also serves as a functional conductive resin that significantly reduces the charging of samples. Our protocol also presents strategies for facilitating the successful cutting of the samples during serial block-face scanning electron microscopy (SBF-SEM) imaging. Our results suggest that the small gold-based pre-embedding vIEM is an ideal labeling method for molecular localization throughout the depth of the sample at subcellular compartments and membrane microdomains.

3D reconstructions of parasite development and the intracellular niche of the microsporidian pathogen E. intestinalis.

Microsporidia are an early-diverging group of fungal pathogens that infect a wide range of hosts. Several microsporidian species infect humans, and infections can lead to fatal disease in immunocompromised individuals. As obligate intracellular parasites with highly reduced genomes, microsporidia are dependent on metabolites from their hosts for successful replication and development. Our knowledge of how microsporidian parasites develop inside the host remains rudimentary, and our understanding of the intracellular niche occupied by microsporidia has thus far relied largely on 2D TEM images and light microscopy. Here, we use serial block face scanning electron microscopy (SBF-SEM) to capture 3D snapshots of the human-infecting microsporidian, Encephalitozoon intestinalis , within host cells. We track the development of E. intestinalis through its life cycle, which allows us to propose a model for how its infection organelle, the polar tube, is assembled de novo in each developing spore. 3D reconstructions of parasite-infected cells provide insights into the physical interactions between host cell organelles and parasitophorous vacuoles, which contain the developing parasites. The host cell mitochondrial network is substantially remodeled during E. intestinalis infection, leading to mitochondrial fragmentation. SBF-SEM analysis shows changes in mitochondrial morphology in infected cells, and live-cell imaging provides insights into mitochondrial dynamics during infection. Together, our data provide insights into parasite development, polar tube assembly, and microsporidia-induced mitochondrial remodeling in the host cell.

Juvenile CLN3 disease is a lysosomal cholesterol storage disorder: similarities with Niemann-Pick type C disease.

BACKGROUND: The most common form of neuronal ceroid lipofuscinosis (NCL) is juvenile CLN3 disease (JNCL), a currently incurable neurodegenerative disorder caused by mutations in the CLN3 gene. Based on our previous work and on the premise that CLN3 affects the trafficking of the cation-independent mannose-6 phosphate receptor and its ligand NPC2, we hypothesised that dysfunction of CLN3 leads to the aberrant accumulation of cholesterol in the late endosomes/lysosomes (LE/Lys) of JNCL patients' brains. METHODS: An immunopurification strategy was used to isolate intact LE/Lys from frozen autopsy brain samples. LE/Lys isolated from samples of JNCL patients were compared with age-matched unaffected controls and Niemann-Pick Type C (NPC) disease patients. Indeed, mutations in NPC1 or NPC2 result in the accumulation of cholesterol in LE/Lys of NPC disease samples, thus providing a positive control. The lipid and protein content of LE/Lys was then analysed using lipidomics and proteomics, respectively. FINDINGS: Lipid and protein profiles of LE/Lys isolated from JNCL patients were profoundly altered compared to controls. Importantly, cholesterol accumulated in LE/Lys of JNCL samples to a comparable extent than in NPC samples. Lipid profiles of LE/Lys were similar in JNCL and NPC patients, except for levels of bis(monoacylglycero)phosphate (BMP). Protein profiles detected in LE/Lys of JNCL and NPC patients appeared identical, except for levels of NPC1. INTERPRETATION: Our results support that JNCL is a lysosomal cholesterol storage disorder. Our findings also support that JNCL and NPC disease share pathogenic pathways leading to aberrant lysosomal accumulation of lipids and proteins, and thus suggest that the treatments available for NPC disease may be beneficial to JNCL patients. This work opens new avenues for further mechanistic studies in model systems of JNCL and possible therapeutic interventions for this disorder. FUNDING: San Francisco Foundation.

[Mechanism of acupuncture-moxibustion with "Biao-Ben" acupoint combination in treating irritable bowel syndrome rats by regulating serum metabolites and metabolic pathway based on TM widely targeted metabolomics method].

OBJECTIVE: To investigate the effect of acupuncture-moxibustion with "Biao-Ben" acupoint combination (BB) on the serum metabolites and metabolic pathway in irritable bowel syndrome (IBS) model rats, so as to explore the mechanisms of BB in the prevention and treatment of IBS. METHODS: Thirty SD rats were randomly divided into three groups: control group, model group, and BB group, with 10 rats in each group. The IBS model was established by the combination of acute stress method and chronic stress method, and the success of the model establishment was evaluated by abdominal wall reflex (AWR). BB group received acupuncture-moxibustion treatment at "Neiguan" (PC6), "Zusanli" (ST36), and "Guanyuan" (CV4) for 15 min, once a day, for a total of 28 days. Bristol's fecal character score was evaluated, and intestinal propulsion rate was calculated. The open-field experiment was used to observe the behaviour of rats. Pathological changes in the colon were observed by H.E. staining. TM widely targeted metabolomics technology was used to detect the metabolic profile of serum samples from 3 groups of rats. Principal component analysis and orthogonal partial least-squares discrimination analysis techniques were combined with database screening to screen differential metabolites, and the KEGG database was utilized to map the enriched metabolic pathway. RESULTS: Compared with the control group, AWR, and the total distance, speed, duration traveled autonomously, the distance of central grid traveling, the number of central grid crossings of the open-field experiment were significantly decreased (P<0.01，P<0.05), while Bristol's fecal character score, intestinal propulsion rate and rest duration in the open-field experiment were significantly increased(P<0.01) in the model group. Compared with the model group, Bristol's fecal character score, the intestinal propulsion rate, rest duration, and rest episode were significantly decreased(P<0.01, P<0.05), while AWR, the total distance, speed, duration traveled autonomously, the distance of central grid traveling, the number of central grid crossings, and the residence time of the central grid were significantly increased(P<0.01，P<0.05) in the BB group. H.E. staining showed a discontinuous mucosal layer of colon tissue, a slightly disordered arrangement of glands, and more inflammatory cell infiltration in the submucosa and muscle layer in the model group, which was relatively milder in the BB group. After comparing the model and control group, 123 differential metabolites were screened, while 57 were screened after comparing the model and BB group. Six differential metabolic pathways were acquired when comparing the model and the control group, while 8 were acquired when comparing the model and BB group using KEGG enrichment analysis, both of which included the arachidonic acid metabolism pathway. CONCLUSION: "Biao-Ben" acupoint combination can improve symptoms of IBS by regulating metabolites of the arachidonic acid metabolism pathway, which may be a potential target for the treatment of IBS.

Mechanisms of gut microbiota-immune-host interaction on glucose regulation in type 2 diabetes.

Intestinal absorption of food is one of the sources of glucose. Insulin resistance and impaired glucose tolerance caused by lifestyle and diet are the precursors of type 2 diabetes. Patients with type 2 diabetes have trouble controlling their blood sugar levels. For long-term health, strict glycemic management is necessary. Although it is thought to be well correlated with metabolic diseases like obesity, insulin resistance, and diabetes, its molecular mechanism is still not completely understood. Disturbed microbiota triggers the gut immune response to reshape the gut homeostasis. This interaction not only maintains the dynamic changes of intestinal flora, but also preserves the integrity of the intestinal barrier. Meanwhile, the microbiota establishes a systemic multiorgan dialog on the gut-brain and gut-liver axes, intestinal absorption of a high-fat diet affects the host's feeding preference and systemic metabolism. Intervention in the gut microbiota can combat the decreased glucose tolerance and insulin sensitivity linked to metabolic diseases both centrally and peripherally. Moreover, the pharmacokinetics of oral hypoglycemic medications are also influenced by gut microbiota. The accumulation of drugs in the gut microbiota not only affects the drug efficacy, but also changes the composition and function of them, thus may help to explain individual therapeutic variances in pharmacological efficacy. Regulating gut microbiota through healthy dietary patterns or supplementing pro/prebiotics can provide guidance for lifestyle interventions in people with poor glycemic control. Traditional Chinese medicine can also be used as complementary medicine to effectively regulate intestinal homeostasis. Intestinal microbiota is becoming a new target against metabolic diseases, so more evidence is needed to elucidate the intricate microbiota-immune-host relationship, and explore the therapeutic potential of targeting intestinal microbiota.

Bacterial contact induces polar plug disintegration to mediate whipworm egg hatching.

The bacterial microbiota promotes the life cycle of the intestine-dwelling whipworm Trichuris by mediating hatching of parasite eggs ingested by the mammalian host. Despite the enormous disease burden associated with Trichuris colonization, the mechanisms underlying this transkingdom interaction have been obscure. Here, we used a multiscale microscopy approach to define the structural events associated with bacteria-mediated hatching of eggs for the murine model parasite Trichuris muris . Through the combination of scanning electron microscopy (SEM) and serial block face SEM (SBFSEM), we visualized the outer surface morphology of the shell and generated 3D structures of the egg and larva during the hatching process. These images revealed that exposure to hatching-inducing bacteria catalyzed asymmetric degradation of the polar plugs prior to exit by the larva. Although unrelated bacteria induced similar loss of electron density and dissolution of the structural integrity of the plugs, egg hatching was most efficient in the presence of bacteria that bound poles with high density such as Staphylococcus aureus . Consistent with the ability of taxonomically distant bacteria to induce hatching, additional results suggest chitinase released from larva within the eggs degrade the plugs from the inside instead of enzymes produced by bacteria in the external environment. These findings define at ultrastructure resolution the evolutionary adaptation of a parasite for the microbe-rich environment of the mammalian gut.

Research progress on acupuncture treatment in central nervous system diseases based on NLRP3 inflammasome in animal models.

Central nervous system (CNS) disorders exhibit complex neurophysiological and pathological mechanisms, which seriously affect the quality of life in patients. Acupuncture, widely accepted as complementary and alternative medicine, has been proven to exert significant therapeutic effects on CNS diseases. As a part of the innate immune system, NLRP3 inflammasome contributes to the pathogenesis of CNS diseases via regulating neuroinflammation. To further explore the mechanisms of acupuncture regulating NLRP3 inflammasome in CNS diseases, our study focused on the effects of acupuncture on neuroinflammation and the NLRP3 inflammasome in vascular dementia, Alzheimer's disease, stroke, depression, and spinal cord injury. This study confirmed that the activation of NLRP3 inflammasome promotes the development of CNS diseases, and inhibiting the activation of NLRP3 inflammasome is a potential key target for the treatment of CNS diseases. In addition, it is concluded that acupuncture alleviates neuroinflammation by inhibiting the activation of the NLRP3 inflammasome pathway, thereby improving the progression of CNS diseases, which provides a theoretical basis for acupuncture to attenuate neuroinflammation and improve CNS diseases.

Capsular Polysaccharide Is Essential for the Virulence of the Antimicrobial-Resistant Pathogen Enterobacter hormaechei.

Nosocomial infections caused by multidrug-resistant (MDR) Enterobacter cloacae complex (ECC) pathogens are on the rise. However, the virulence strategies employed by these pathogens remain elusive. Here, we study the interaction of ECC clinical isolates with human serum to define how this pathogen evades the antimicrobial action of complement, one of the first lines of host-mediated immune defense. We identified a small number of serum-sensitive strains, including Enterobacter hormaechei strain NR3055, which we exploited for the in vitro selection of serum-resistant clones. Comparative genomics between the serum-sensitive NR3055 strain and the isolated serum-resistant clones revealed a premature stop codon in the wzy gene of the capsular polysaccharide biosynthesis locus of NR3055. The complementation of wzy conferred serum resistance to NR3055, prevented the deposition of complement proteins on the bacterial surface, inhibited phagocytosis by human neutrophils, and rendered the bacteria virulent in a mouse model of peritonitis. Mice exposed to a nonlethal dose of encapsulated NR3055 were protected from subsequent lethal infections by encapsulated NR3055, whereas mice that were previously exposed to unencapsulated NR3055 succumbed to infection. Thus, capsule is a key immune evasion determinant for E. hormaechei, and it is a potential target for prophylactics and therapeutics to combat these increasingly MDR human pathogens. IMPORTANCE Infections caused by antimicrobial resistant bacteria are of increasing concern, especially those due to carbapenem-resistant Enterobacteriaceae pathogens. Included in this group are species of the Enterobacter cloacae complex, regarding which there is a paucity of knowledge on the infection biology of the pathogens, despite their clinical relevance. In this study, we combine techniques in comparative genomics, bacterial genetics, and diverse models of infection to establish capsule as an important mechanism of Enterobacter pathogens to resist the antibacterial activity of serum, a first line of host defense against bacterial infections. We also show that immune memory targeting the Enterobacter capsule protects against lethal infection. The further characterization of Enterobacter infection biology and the immune response to infection are needed for the development of therapies and preventative interventions targeting these highly antibiotic resistant pathogens.

[Clinical research of acupuncture therapy combined with domperidone in treatment of diabetic gastroparesis of liver stagnation and spleen deficiency].

OBJECTIVE: To observe the clinical efficacy of shuanggu yitong acupuncture therapy (the therapy for both replenishment and unblocking) combined with domperidone on diabetic gastroparesis (DGP) of liver stagnation and spleen deficiency pattern and explore its effect mechanism. METHODS: DGP patients differentiated as liver stagnation and spleen deficiency pattern were divided into a control group (n=42) and an observation group (n=42) according to the random number table. The patients in the control group took domperidone tablets orally, 10 mg each time, 3 times a day for 28 days. In the observation group, on the base of the treatment as the control group, shuanggu yitong acupuncture therapy was applied to Baihui (GV20), Shenting (GV24), Zhongwan (CV12), bilateral Zusanli (ST36), Hegu (LI4)and Taichong (LR3), stimulated for 30 min in each treatment. Acupuncture was given once daily, 3 times a weeks for 28 days consecutively. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG) and glycosylated hemoglobin (HbA1c) were detected before and after treatment in the patients of two groups separately. The score of symptom severity index of gastroparesis (GCSI), traditional Chinese medicine (TCM) syndrome score and gastric emptying rate were assessed in the patients of two groups. Using ELISA, radioimmunoassay and colorimentry methods, the contents of motilin in plasma, gastrin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and interferon-gamma (INF-γ) in serum, as well as the activity of superoxide dismutase (SOD), reactive oxygen species (ROS) and malondialdehyde (MDA) in the serum were determined in the two groups. The clinical curative effect was evaluated. RESULTS: After treatment, the levels of FBG, 2 h PBG and HbA1c, the scores of GCSI and TCM syndrome, the contents of motilin in plasma, gastrin, TNF-α and MDA, as well as the activity of ROS in serum were all reduced when compared with those before treatment in each group (P<0.05, P<0.01), while gastric emptying rate and SOD activity in the serum were higher than those before treatment (P<0.05, P<0.01). After treatment, the serological content of INF-γ was lower than that before treatment in the control group (P<0.05), and the contents of IL-6 and IL-1ß were reduced than those before treatment in the observation group (P<0.05). Compared with the control group, the levels of FBG, 2 h PBG and HbA1c, the scores of GCSI and TCM symptoms, the contents of motilin in plasma, gastrin, TNF-α, MDA, IL-6 and IL-1ß, and the activity of ROS in serum in the observation group were all lower significantly (P<0.05, P<0.01), while the SOD activity and gastric emptying rate in the observation group were higher than those in the control group (P<0.05, P<0.01). The total effective rate was 90.5% (38/42) in the observation group, better than the control group (73.8%, 31/42, P<0.05). CONCLUSION: Shuanggu yitong acupuncture therapy combined with domperidone remarkably relieves the clinical symptoms and improves the gastric emptying rate, effectively reduces motilin and gastrin and regulates oxidative stress and inflammatory responses in the patients with DGP of liver stagnation and spleen deficiency.

A Simple-Structured Perovskite Wavelength Sensor for Full-Color Imaging Application.

In this study, simple-structured wavelength sensors were developed by depositing two back-to-back Au/MAPbI3/Au photodetectors on an MAPbI3 single crystal. This sensor could quantitatively distinguish wavelengths. Further device analysis showed that both photodetectors possess entirely disparate optoelectronic properties. Consequently, the as-developed wavelength sensor could accurately distinguish incident-light wavelengths ranging from 265 to 860 nm with a resolution of less than 1.5 nm based on the relation between the photocurrent ratios of both photodetectors and the incident light wavelengths. Notably, a high resolution and wide detection range are among the optimum reported values for such sensors and enable full-color imaging. Furthermore, technology computer-aided design (TCAD) simulations showed that a mechanism involved in distinguishing wavelengths is attributed to the wavelength-dependent photon generation rate in MAPbI3 single crystals. The high-performance MAPbI3 wavelength sensor can potentially drive the research progress of perovskites in wavelength recognition and full-color imaging.

Relationship between acupuncture and transient receptor potential vanilloid: Current and future directions.

Acupuncture is a common complementary and alternative therapy around the world, but its mechanism remains still unclear. In the past decade, some studies indicated that transient receptor potential vanilloid (TRPV) channels play a great role in the response of acupuncture stimulation. In this article, we discussed the relationship between acupuncture and TRPV channels. Different from inhibitors and agonists, the regulation of acupuncture on TRPV channels is multi-targeted and biphasic control. Acupuncture stimulation shows significant modulation on TRPV1 and TRPV4 at the autonomic nervous system (ANS) including central and peripheral nervous systems. On the contrary, the abundant expression and functional participation of TRPV1 and TRPV4 were specific to acupuncture stimulation at acupoints. The enhancement or inhibition of TRPV channels at different anatomical levels will affect the therapeutic effect of acupuncture. In conclusion, TRPV channels help to understand the principle of acupuncture stimulation, and acupuncture also provides a potential approach to TRPV-related trials.