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Rhizopus oryzae is a destructive pathogen that frequently causes tobacco pole rot in curing chambers. Phenotypic characterization of the pathogen was conducted to provide basic biological and pathological information using Biolog Phenotype MicroArray (PM). In addition, the Y5 strain of R. oryzae was sequenced using Illumina HiSeq and Pacific Biosciences (PacBio) technologies. Using PM plates 1–8, 758 growth conditions were tested. Results indicated that R. oryzae could metabolize 54.21% of tested carbon sources, 86.84% of nitrogen sources, 100% of sulfur sources, and 98.31% of phosphorus sources. About 37 carbon compounds, including D-xylose, N-acetyl-D-glucosamine, D-sorbitol, β-methyl-D-glucoside, D-galactose, L-arabinose, and D-cellobiose, significantly supported the growth of the pathogen. PM 3 indicated the active nitrogen sources, including Gly-Asn, Ala-Asp., Ala-Gln, and uric acid. PM 6–8 showed 285 different nitrogen pathways, indicating that different combinations of different amino acids support the growth of the pathogen. Genome sequencing results showed that the R. oryzae Y5 strain had raw data assembled into 2,271 Mbp with an N50 value of 10,563 bp. A genome sequence of 50.3 Mb was polished and assembled into 53 contigs with an N50 length of 1,785,794 bp, maximum contig length of 3,223,184 bp, and a sum of contig lengths of 51,182,778 bp. A total of 12,680 protein-coding genes were predicted using the Nonredundant, Gene Ontology, Clusters of Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes, and SWISS-PROT databases. The genome sequence and annotation resources of R. oryzae provided a reference for studying its biological characteristics, trait-specific genes, pathogen-host interaction, pathogen evolution, and population genetic diversity. The phenomics and genome of R. oryzae will provide insights into microfungal biology, pathogen evolution, and the genetic diversity of epidemics.

For a long time, the epidemic situation of hemorrhagic fever with renal syndrome (HFRS) caused by hantavirus (HV) in Yunnan Province of China has been relatively severe. The molecular epidemiology and host characteristics of HV in Yunnan Province are still not completely clear, and the systematic and long-term investigation of the epidemic area is very limited. In this study, a total of 488 murine-shaped animals were captured in the three regions of Mile City, Mangshi City and Lianghe County in Yunnan Province, and then the type of HV was identified by multiplex real-time RT-PCR and sequenced. The results indicate that 2.46% of the murine-shaped animal specimens were infected with HV. A new subtype of Seoul virus (SEOV) was found in the rare rat species Rattus nitidus in Lianghe County, and the two strains of this new subtype were named YNLH-K40 and YNLH-K53. Through the phylogenetic analysis of this new subtype, it is shown that this new subtype is very similar to the type S5 of SEOV, which is previously described as the main cause for the high incidence of HFRS in Longquan City, Zhejiang Province, China. This new subtype is highly likely to cause human infection and disease. Therefore, in addition to further promoting the improvement of the HV gene database and strengthening the discovery and monitoring of the host animals in Yunnan Province, more attention should be paid to the pathogenic potential of the newly discovered HV type.

Objective: Untreated protracted bacterial bronchitis (PBB), a chronic wet cough prevalent in children, may lead to chronic suppurative lung disease or bronchiectasis. However, clinical diagnostic criteria for PBB are nonspecific; thus, PBB may be misdiagnosed. Thus, we assessed the diagnostic value of fiberoptic bronchoscopy (FOB) and risk factors associated with PBB. Methods: Children with chronic cough at First Affiliated Hospital of Anhui Medical University from January 2015 to May 2020 were enrolled and allocated to a suspected PBB (n=141) or a non-PBB (n=206) group. All children underwent extensive laboratory, chest imaging, and allergen tests. Children with suspected PBB underwent FOB with bronchoalveolar lavage; lavage and sputum samples were cultured. Results: All 347 children had chronic wet cough for approximately 2 months. Of 141 children with suspected PBB, 140 received FOB with bronchoalveolar lavage. Visible tracheal changes included pale mucosa, mucosal congestion, edema, swelling, and increased secretions attached to the wall. Sputum was visible primarily in the left main bronchus (78.7%), left lower lobe (59.6%), right upper lobe (62.4%), and right lower lobe (64.5%). Sputum properties and amounts significantly differed between children with vs. without PBB ( P < 0.05). Dermatophagoides (odds ratio [OR], 2.642; 95% CI, 1.283–5.369) and milk protein (OR, 2.452; 95% CI, 1.243–4.836) allergies and eczema (OR, 1.763; 95% CI, 1.011–3.075) were risk factors significantly associated with PBB. Conclusion: Dermatophagoides, milk protein, and eczema were associated with increased risk of PBB. Sputum distribution and tracheal wall changes observed through FOB may distinguish PBB and assist in its diagnosis.

As one of the most environmentally toxic heavy metals, cadmium (Cd) has attracted the attention of researchers globally. In particular, Guangxi, a province in southwestern China, has been subjected to severe Cd pollution due to geogenic processes and anthropogenic activities. Cd can be accumulated in aquatic animals and transferred to the human body through the food chain, with potential health risks. The aim of the present study was to explore the effects of waterborne Cd exposure (0.5 mg/L and 1.5 mg/L) on the intestinal microbiota of mudsnail, Cipangopaludina cathayensis, which is favored by farmers and consumers in Guangxi. Gut bacterial community composition was investigated using high-throughput sequencing of the V3–V4 segment of the bacterial 16S rRNA gene. Our results indicated that C. cathayensis could tolerate low Cd (0.5 mg/L) stress, while Cd exposure at high doses (1.5 mg/L) exerted considerable effects on microbiota composition. At the phylum level, Proteobacteria, Bacteroidetes, and Firmicutes were the dominant phyla in the mudsnail gut microbiota. The relative abundances of Bacteroidetes increased significantly under high Cd exposure (H14) (p < 0.01), with no significant change in the low Cd exposure (L14) treatment. The dominant genera with significant differences in relative abundance were Pseudomonas, Cloacibacterium, Acinetobacter, Dechloromonas, and Rhodobacter. In addition, Cd exposure could significantly alter the pathways associated with metabolism, cellular processes, environmental information processing, genetic information processing, human diseases, and organismal systems. Notably, compared to the L14 treatment, some disease-related pathways were enriched, while some xenobiotic and organic compound biodegradation and metabolism pathways were significantly inhibited in the H14 group. Overall, Cd exposure profoundly influenced community structure and function of gut microbiota, which may in turn influence C. cathayensis gut homeostasis and health.

Phyllospheric microbial composition of tobacco (Nicotiana tabacum L.) is contingent upon certain factors, such as the growth stage of the plant, leaf position, and cultivar and its geographical location, which influence, either directly or indirectly, the growth, overall health, and production of the tobacco plant. To better understand the spatiotemporal variation of the community and the divergence of phyllospheric microflora, procured from healthy and diseased tobacco leaves infected by Alternaria alternata, the current study employed microbe culturing, high-throughput technique, and BIOLOG ECO. Microbe culturing resulted in the isolation of 153 culturable fungal isolates belonging to 33 genera and 99 bacterial isolates belonging to 15 genera. High-throughput sequencing revealed that the phyllosphere of tobacco was dominantly colonized by Ascomycota and Proteobacteria, whereas, the most abundant fungal and bacterial genera were Alternaria and Pseudomonas. The relative abundance of Alternaria increased in the upper and middle healthy groups from the first collection time to the third, whereas, the relative abundance of Pseudomonas, Sphingomonas, and Methylobacterium from the same positions increased during gradual leaf aging. Non-metric multi-dimensional scaling (NMDs) showed clustering of fungal communities in healthy samples, while bacterial communities of all diseased and healthy groups were found scattered. FUNGuild analysis, from the first collection stage to the third one in both groups, indicated an increase in the relative abundance of Pathotroph-Saprotroph, Pathotroph-Saprotroph-Symbiotroph, and Pathotroph-Symbiotroph. Inclusive of all samples, as per the PICRUSt analysis, the predominant pathway was metabolism function accounting for 50.03%. The average values of omnilog units (OUs) showed relatively higher utilization rates of carbon sources by the microbial flora of healthy leaves. According to the analysis of genus abundances, leaf growth and leaf position were the important drivers of change in structuring the microbial communities. The current findings revealed the complex ecological dynamics that occur in the phyllospheric microbial communities over the course of a spatiotemporal varying environment with the development of tobacco brown spots, highlighting the importance of community succession.

The islet of Langerhans contains at least five types of endocrine cells producing distinct hormones. In response to nutrient or neuronal stimulation, islet endocrine cells release biochemicals including peptide hormones to regulate metabolism and to control glucose homeostasis. It is now recognized that malfunction of islet cells, notably insufficient insulin release of β-cells and hypersecretion of glucagon from α-cells, represents a causal event leading to hyperglycemia and frank diabetes, a disease that is increasing at an alarming rate to reach an epidemic level worldwide. Understanding the mechanisms regulating stimulus-secretion coupling and investigating how islet β-cells maintain a robust secretory activity are important topics in islet biology and diabetes research. To facilitate such studies, a number of biological systems and assay platforms have been developed for the functional analysis of islet cells. These technologies have enabled detailed analyses of individual islets at the cellular level, either in vitro, in situ, or in vivo.

Pancreatic β-cells respond to metabolic stress by upregulating insulin secretion, however the underlying mechanisms remain unclear. In β-cells from overweight humans without diabetes, and mice fed a high-fat diet for 2 days, insulin exocytosis and secretion are enhanced without increased Ca2+influx. β-cell RNA-seq suggests altered metabolic pathways early following HFD, where we find increased basal oxygen consumption, proton leak, but a more reduced cytosolic redox state. Increased β-cell exocytosis after 2-day HFD is dependent on this reduced intracellular redox and requires thesentrin-specific SUMO-protease-1(SENP1). Mice with either pancreas- or β-cell-specific SENP1 deletion fail to up-regulate exocytosis and become rapidly glucose intolerant after 2-day HFD. Mechanistically, redox-sensing by SENP1 requires a thiol group at C535 which together with Zn+-binding suppresses basal protease activity and unrestrained β-cell exocytosis and increases SENP1 sensitivity to regulation by redox signals.

Amino acid metabolism in vascular endothelium is important for sprouting angiogenesis. SLC38A5 (solute carrier family 38 member 5), an amino acid (AA) transporter, shuttles neutral AAs across cell membrane, including glutamine, which may serve as metabolic fuel for proliferating endothelial cells (ECs) to promote angiogenesis. Here we found thatSlc38a5is highly enriched in normal retinal vascular endothelium, and more specifically in pathological sprouting neovessels.Slc38a5is suppressed in retinal blood vessels fromLrp5-/-andNdpy/-mice, both genetic models of defective retinal vascular development with Wnt signaling mutations. Additionally,Slc38a5transcription is directly regulated by Wnt/β-catenin signaling. Genetic deficiency ofSlc38a5in mice substantially delays retinal vascular development and suppresses pathological neovascularization in oxygen-induced retinopathy modeling ischemic proliferative retinopathies. Inhibition ofSLC38A5in retinal vascular ECs impairs EC proliferation and angiogenic function, suppresses glutamine uptake, and dampens vascular endothelial growth factor receptor 2 (VEGFR2). Together these findings suggest that SLC38A5 is a new metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in ECs.Significance StatementAmino acid metabolism in vascular endothelium is important for angiogenesis. SLC38A5 (solute carrier family 38 member 5) is an amino acid (AA) transporter for shuttling neutral AAs such as glutamine across cell membrane. Our work demonstrate thatSlc38a5is highly enriched in retinal vascular endothelium. SLC38A5 regulates endothelial cell glutamine uptake and vascular growth factor receptors to impact blood vessels growth in retinal development and in retinopathies. This work uncovered a novel role of SLC38A5 as a metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in blood vessel endothelium. Findings from this study also suggest that targeting SLC38A5 or relevant AAs can be a new way to protect against retinopathy.

In this work, a method for the determination of berberine in Rhizoma coptidis using β-cyclodextrin-sensitized fluorescence technology is established. Berberine is the main extract of Rhizoma coptidis, a medicinal material, which causes an envelope reaction with β-cyclodextrin to generate fluorescence sensitization. In the environment of its own aqueous extract, with 0.0065 mol L−1 of β-cyclodextrin, a fluorescence excitation wavelength (λex) of 345 nm and an emission wavelength (λem) of 540 nm were selected to avoid interference from other distractors. The fluorescent sensor for the detection of berberine exhibits a low limit of detection (3.59 × 10−9 mol L−1) and a wide linear range from 2.7 × 10−7 mol L−1 to 2.7 × 10−6 mol L−1. Our sensor can be also used to detect berberine in real medicinal materials. The content of berberine in Rhizoma coptidis medicinal material was found to be 7.60% using this method with an average recovery rate of 99.5%. The result obtained by thin-layer chromatography with fluorescence detection was 7.61%, which is consistent with the result from the β-cyclodextrin sensitized fluorescence method. This method is simple and environmentally friendly with high sensitivity and good selectivity and gives reliable results, which is promising for practical application.

Amino acid (AA) metabolism in vascular endothelium is important for sprouting angiogenesis. SLC38A5 (solute carrier family 38 member 5), an AA transporter, shuttles neutral AAs across cell membrane, including glutamine, which may serve as metabolic fuel for proliferating endothelial cells (ECs) to promote angiogenesis. Here, we found that Slc38a5 is highly enriched in normal retinal vascular endothelium, and more specifically, in pathological sprouting neovessels. Slc38a5 is suppressed in retinal blood vessels from Lrp5−/− and Ndpy/− mice, both genetic models of defective retinal vascular development with Wnt signaling mutations. Additionally, Slc38a5 transcription is regulated by Wnt/β-catenin signaling. Genetic deficiency of Slc38a5 in mice substantially delays retinal vascular development and suppresses pathological neovascularization in oxygen-induced retinopathy modeling ischemic proliferative retinopathies. Inhibition of SLC38A5 in human retinal vascular ECs impairs EC proliferation and angiogenic function, suppresses glutamine uptake, and dampens vascular endothelial growth factor receptor 2. Together these findings suggest that SLC38A5 is a new metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in ECs.

The innovation and patent layout of traditional Chinese medicine compounds reflects the innovation level of the traditio-nal Chinese medicine industry to a certain extent. Lianhua Qingwen Formula was taken as an example to analyze the innovation and patent layout of traditional Chinese medicine compounds. The study first proposed an innovative technology system for traditional Chinese medicine compounds, and then analyzed the advantages and disadvantages of Lianhua Qingwen Formula in innovation and patent layout based on 56 patents and other relevant patents. The analysis results showed that Lianhua Qingwen Formula had the following characte-ristics in terms of patent layout. In terms of innovation technical route, the patented technical route of Lianhua Qingwen Formula was mainly based on the composition and preparation of granules as the first choice, followed by corresponding process improvements, new uses, and detection methods as the main improvement routes. In terms of the corresponding patent layout, the basic patent protection scope of Lianhua Qingwen Formula completely covered marketed drugs, and then took new functions as the main layout strategy for subsequent patent applications. With the advancement of modern technical means, the preparation process and testing methods have been optimized continuously. At the same time, the international patent layout was given the priority in domestic patent application. Based on the above characteristics, the study gave suggestions for follow-up innovation and patent work for Lianhua Qingwen Formula, so as to provide enlightenment for other traditional Chinese medicine companies in exploring original innovation of traditional Chinese medicine compounds, improving innovative methods, and enhancing the ability of patent layout of innovative achievements.

Appropriate insulin secretion is essential for maintaining euglycemia, and impairment or loss of insulin release represents a causal event leading to diabetes. There have been extensive efforts of studying insulin secretion and its regulation using a variety of biological preparations, yet it remains challenging to monitor the dynamics of insulin secretion at the cellular level in the intact pancreas of living animals, where islet cells are supplied with physiological blood circulation and oxygenation, nerve innervation, and tissue support of surrounding exocrine cells. Herein we presented our pilot efforts of ZIMIR imaging in pancreatic islet cells in a living mouse. The imaging tracked insulin/Zn2+ release of individual islet β-cells in the intact pancreas with high spatiotemporal resolution, revealing a rhythmic secretion activity that appeared to be synchronized among islet β-cells. To facilitate probe delivery to islet cells, we also developed a chemogenetic approach by expressing the HaloTag protein on the cell surface. Finally, we demonstrated the application of a fluorescent granule zinc indicator, ZIGIR, as a selective and efficient islet cell marker in living animals through systemic delivery. We expect future optimization and integration of these approaches would enable longitudinal tracking of beta cell mass and function in vivo by optical imaging.

In this work, reasons for the spectral difference between two isoflavones, Formononetin (F) and ononin (FG), are explained in the viewpoint of molecular structure through a comparison study of the fluorescence features of the two. The fluorescence enhancement of FG in hot alkaline condition is reported for the first time. For F, there was almost no fluorescence under acidic conditions, but when pH>5, its fluorescence began to increase with increasing pH due to the proton ionization of 7-OH. In the range of pH 9.3-12.0, the anion form of F produced a fairly strong and stable fluorescence with maximum excitation wavelength (λex) of 334 nm and emission wavelength (λem) of 464 nm, its fluorescence quantum yield (Yf) was measured to be 0.042. And for FG, its aqueous solution fluoresced weakly in a wide pH range until it was placed under hot alkaline conditions, which was presumed to the cleavage reaction of the γ-pyrone ring in FG by observing a significant fluorescence at λex / λem =288 / 388nm, and Yf was determined to be 0.020. The fluorescence sensitization methods of F and FG both exhibit low limits of detection (2.60 ng·mL-1, 9.30 ng·mL-1) and wide linear ranges (0.0117-1.86 μg·mL-1, 0.0146-2.92μg·mL-1). Although the structural relationship between F and FG is glycoside and aglycone, FG cannot be translated to F by glucoside hydrolysis under hot alkaline condition, the fluorescence enhancement mechanisms of the two are essentially different. The fluorescence difference between the two under different experimental conditions lays the foundation for future fluorescence quantitative analysis.

Ocean warming can have significant negative impacts on population genetic diversity, local endemism and geographical distribution of a wide range of marine organisms. Thus, the identification of conservation units with high risk of extinction becomes an imperative task to assess, monitor, and manage marine biodiversity for policy-makers. Here, we surveyed population structure and genetic variation of the red seaweed Gracilaria vermiculophylla along the coast of China using genome-based amplified fragment length polymorphism (AFLP) scanning. Regardless of analysis methods used, AFLP consistently revealed a south to north genetic isolation. Populations at the southern coast of China showed unique genetic variation and much greater allelic richness, heterozygosity, and average genetic diversity than the northern. In particular, we identified a geographical barrier that may hinder genetic exchange between the two lineages. Consequently, the characterized genetic lineage at the southern coast of China likely resulted from the interplay of post-glacial persistence of ancestral diversity, geographical isolation and local adaptation. In particular, the southern populations are indispensable components to explore evolutionary genetics and historical biogeography of G. vermiculophylla in the northwestern Pacific, and the unique diversity also has important conservation value in terms of projected climate warming.

Pseudocrossocheilus bamaensis is endemic to the upstream of Xijiang River, Guangxi, China and its natural population has been declining due to overfishing and habitat destruction. Here, we first report the complete mitogenome of this species, which is 16,594 bp in length, containing 13 protein-coding genes, 22 tRNA genes, two rRNA genes, as well as a putative light strand origin of replication (OL) and a putative control region (D-loop). The overall base composition is 31.8% of A, 15.7% of G, 26.8% of T and 25.7% of C, with a high A + T content (58.6%). Phylogenetic analysis suggests that P. bamaensis is closely related to Ptychidio jordani and Rectoris posehensis. These results will contribute to the molecular evolution and phylogenetic research of Labeoninae and further protection of its fish species.

Regulated secretion is a fundamental cellular process that serves diverse functions in neurobiology, endocrinology, immunology, and numerous other aspects of animal physiology. In response to environmental or biological cues, cells release contents of secretory granules into an extracellular medium to communicate with or impact neighboring or distant cells through paracrine or endocrine signaling. To investigate mechanisms governing stimulus-secretion coupling, to better understand how cells maintain or regulate their secretory activity, and to characterize secretion defects in human diseases, probes for tracking various exocytotic events at the cellular or sub-cellular level have been developed over the years. This review summarizes different strategies and recent progress in developing optical probes for monitoring regulated secretion in mammalian cells.

Objective: This study aims to evaluate the effectiveness of individualized hemodialysis for unconventional hypotension in diabetic nephropathy patients. Methods: A total of 60 patients were selected and randomly divided into study group and control group. The control group used the standard dialysis model, while the study group used the individualized hemodialysis scheme, in which the dialysis was performed using an individualized dialysis machine temperature control, pattern of natrium, and pattern of step ultrafiltration in combination with dialysate-containing glucose. Results: The total occurrence rate of hypotension, dry weight standard-reaching rate, and blood quality during and after dialysis in the study group were superior to those in the control group ( P 0.05). Conclusion: The combined application of low temperature, pattern of natrium, pattern of step ultrafiltration, and dialysate-containing glucose individualization is safe and effective for preventing and controlling the occurrence of intradialytic hypotension (IDH), improve symptoms, and improve the dry weight standard-reaching rate.

Ephedrae Herba (EH, Ephedra sinica Stapf.) and Armeniacae Semen Amarum (ASA, Prunus armeniaca L. var. ansu Maxim.) have been used to treat asthma, cold, fever, and cough in China for thousands of years.In this study, we aimed to investigate the optimal ratio of EH and ASA compatibility (EAC) to reduce airway injury in asthmatic rats and its possible mechanism.Rats were sensitized with a mixture of acetylcholine chloride and histamine bisphosphate 1 h before sensitization by intragastric administration of EAC or dexamethasone or saline for 7 days. Subsequently, the ultrastructure of rat airway epithelial tissue changes, apoptosis of the airway epithelial cells, and the expression of mRNA and protein of EGRF and Bcl-2 were detected.Transmission electron microscope: EAC (groups C and E) had the most prominent effect on repairing airway epithelial cells' ultrastructural changes in asthmatic rats. TUNEL: dexamethasone and EAC (groups B、C、E and F) inhibited the apoptosis of airway epithelial cells in asthmatic rats (P 0.05). In situ hybridization: EAC (group E) inhibited the overexpression of EGFR and Bcl-2 mRNA (P 0.05).Western Blotting: EAC (groups A、B、C、E and F) inhibited the upregulation of airway epithelial EGFR and Bcl-2 protein expression (P 0.01).Our findings indicate that EAC can inhibit abnormal changes in airway epithelial structure and apoptosis of airway epithelial cells, thereby alleviating airway injury. In this study, the best combination of EH and ASA to alleviate airway epithelial injury in asthmatic rats was group E (EH: ASA = 8: 4.5).

MicroRNAs are small non-coding RNAs acting as posttranscriptional repressors of gene expression. Identifying mRNA targets of a given miRNA remains an outstanding challenge in the field. We have developed a new experimental approach, TargetLink, that applied locked nucleic acid (LNA) as the affinity probe to enrich target genes of a specific microRNA in intact cells. TargetLink also consists a rigorous and systematic data analysis pipeline to identify target genes by comparing LNA-enriched sequences between experimental and control samples. Using miR-21 as a test microRNA, we identified 12 target genes of miR-21 in a human colorectal cancer cell by this approach. The majority of the identified targets interacted with miR-21 via imperfect seed pairing. Target validation confirmed that miR-21 repressed the expression of the identified targets. The cellular abundance of the identified miR-21 target transcripts varied over a wide range, with some targets expressed at a rather low level, confirming that both abundant and rare transcripts are susceptible to regulation by microRNAs, and that TargetLink is an efficient approach for identifying the target set of a specific microRNA in intact cells. C20orf111, one of the novel targets identified by TargetLink, was found to reside in the nuclear speckle and to be reliably repressed by miR-21 through the interaction at its coding sequence.

Mitochondrial metabolism plays an integral role in glucose-stimulated insulin secretion (GSIS) in β-cells. In addition, the diabetogenic role of glucagon released from α-cells plays a major role in the etiology of both type 1 and type 2 diabetes because unopposed hyperglucagonemia is a pertinent contributor to diabetic hyperglycemia. Titrating expression levels of the mitochondrial protein mitoNEET is a powerful approach to fine-tune mitochondrial capacity of cells. Mechanistically, β-cell–specific mitoNEET induction causes hyperglycemia and glucose intolerance due to activation of a Parkin-dependent mitophagic pathway, leading to the formation of vacuoles and uniquely structured mitophagosomes. Induction of mitoNEET in α-cells leads to fasting-induced hypoglycemia and hypersecretion of insulin during GSIS. MitoNEET-challenged α-cells exert potent antiapoptotic effects on β-cells and prevent cellular dysfunction associated with mitoNEET overexpression in β-cells. These observations identify that reduced mitochondrial function in α-cells exerts potently protective effects on β-cells, preserving β-cell viability and mass.

The pleiotropic actions of adiponectin in improving cell survival and metabolism have motivated the development of small-molecule therapeutic agents for treating diabetes and lipotoxicity. AdipoRon is a synthetic agonist of the adiponectin receptors, yet is limited by its poor solubility and bioavailability. In this work, we expand on the protective effects of AdipoRon in pancreatic β-cells and examine how structural modifications could affect the activity, pharmacokinetics, and bioavailability of this small molecule. We describe a series of AdipoRon analogs containing amphiphilic ethylene glycol (PEG) chains. Among these, AdipoRonPEG5 induced pleiotropic effects in mice under insulinopenic and high-fat diet (HFD) conditions. While both AdipoRon and AdipoRonPEG5 substantially attenuate palmitate-induced lipotoxicity in INS-1 cells, only AdipoRonPEG5 treatment is accompanied by a significant reduction in cytotoxic ceramides. In vivo, AdipoRonPEG5 can substantially reduce pancreatic, hepatic, and serum ceramide species, with a concomitant increase in the corresponding sphingoid bases and improves insulin sensitivity of mice under HFD feeding conditions. Furthermore, hyperglycemia in streptozotocin (STZ)-induced insulinopenic adiponectin-null mice is also attenuated upon AdipoRonPEG5 treatment. Our results suggest that AdipoRonPEG5 is more effective in reducing ceramides and dihydroceramides in the liver of HFD-fed mice than AdipoRon, consistent with its potent activity in activating ceramidase in vitro in INS-1 cells. Additionally, these results indicate that the beneficial effects of AdipoRonPEG5 can be partially attributed to improved pharmacokinetics as compared with AdipoRon, thus suggesting that further derivatization may improve affinity and tissue-specific targeting., Graphical abstract

Background This study aims to examine the effect of supportive psychological intervention (SPI) on psychological disorders (PD) in clinical medicine students (CMS) with English Learning Difficulties (ELD). Methods We will perform a comprehensive literature search from the following databases: Cochrane Library, MEDLINE, EMBASE, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All databases will be performed from their inception to the present without language limitation by 2 independent reviewers. We will also look for grey literature, such as conference proceedings, dissertations or theses. Newcastle-Ottawa Scale will be used to assess study quality, and RevMan 5.3 software will be applied to carry out statistical analysis. Results This study will summarize the most recent evidence to assess the effect of SPI on PD in CMS with ELD. Conclusion This study may provide helpful evidence of SPI on PD in CMS with ELD. OSF REGISTRATION NUMBER:: osf.io/tah2s.

Numerous mammalian cells contain abundant Zn(2+) in their secretory granules, yet available Zn(2+) sensors lack the desired specificity and sensitivity for imaging granular Zn(2+). We developed a fluorescent zinc granule indicator, ZIGIR, that possesses numerous desired properties for live cell imaging, including >100-fold fluorescence enhancement, membrane permeability, and selective enrichment to acidic granules. The combined advantages endow ZIGIR with superior sensitivity and specificity for imaging granular Zn(2+). ZIGIR enables separation of heterogenous β cells based on their insulin content and sorting of mouse islets into pure α cells and β cells. In human islets, ZIGIR facilitates sorting of endocrine cells into highly enriched α cells and β cells, reveals unexpectedly high Zn(2+) activity in the somatostatin granule of some δ cells, and uncovers variation in the glucagon content among human α cells. We expect broad applications of ZIGIR for studying Zn(2+) biology and Zn(2+)-rich secretory granules and for engineering β cells with high insulin content for treating diabetes.

Photovoltaic power generation is one of the best ways to utilize solar energy, but the cost of electricity is very high. To reduce the cost of photovoltaic power generation, in this paper, a type of planar luminescent solar concentrator waveguides based on Lumogen F Red 305 (LR305) dye with each size of 50 mm×50 mm×5 mm was proposed with radical polymerization method. The optical properties and photo-electricity outputs of the waveguides were characterized.

Flavanone derivatives are important active ingredients of natural medicine, so the synthesis of these compounds is one of the research hotspots of organic synthesis. Nevertheless, there is little research on fluorescence properties of these compounds up to now. Fluorescence properties of flavanone and 6 kinds of hydroxyl derivatives are studied in this paper. It is found that aqueous solutions of flavanone (FV), 7-hydroxyflavanone (7HF) and 6-hydroxyflavanone (6HF) have fluorescence, but aqueous solutions of 2’-hydroxyflavanone (2’HF), 4’-hydroxyflavanone (4’HF), naringenin and pinocembrin basically have no fluorescence. In three dimensional fluorescence spectra, excitation wavelengths λex of FV are located at 235, 265 and 340 nm, emission wavelength λem is at 386 nm; λex of 7HF are at 230, 276 and 315 nm, λem is at 391 nm; λex of 6HF are at 260 and 356 nm, em is at 482 nm. Influences of pH on fluorescence of FV, 7HF and 6HF are studied, and the reasons of pH affects on fluorescence are discussed from the viewpoint of molecular structure. The UV-absorption spectra of 7HF and 6HF at different pH are studied, and the proton ionization constants (pKa) of 7HF and 6HF are determined respectively to be 7.26±0.05 and 9.90±0.02, by a pH-absorption method. Influences of solvent (methanol) on fluorescence of FV, 7HF and 6HF are studied, and find that the fluorescence of FV and 7HF in methanol are weaker than that in water, but the fluorescence of 6HF in methanol is much stronger. In ordered media (SDS, CTAB and β-CD), fluorescence of FV and 7HF decreased than that in water, but the fluorescence of 6HF enhanced in the media of β-CD or CTAB. Using quinine sulfate or L-tryptophane as reference, fluorescence quantum yields of FV and 7HF aqueous solutions are measured to be 0.057 and 0.012, respectively; fluorescence quantum yields of 6HF in methanol or in aqueous solution containing 1.62 mg·mL-1 β-CD are measured to be 0.064 or 0.012, respectively.

The pancreatic islet beta cell plays an essential role in maintaining the normal blood glucose level by releasing insulin. Loss of functional beta cell mass leads to diabetes—a disease affecting ∼9% of the population worldwide. There has been great interest and intense effort in developing imaging probes for monitoring islet beta cells, and glucagon-like peptide-1 receptor (GLP-1R) has emerged as a valuable biomarker for targeting beta cells. However, efforts thus far in GLP-1R mediated beta cell labeling and imaging has largely, if not exclusively, focused on developing imaging probes for monitoring beta cell mass, and few studies have investigated imaging beta cell function (insulin release) through GLP-1R. We now report the design and synthesis of a bioconjugate, ZIMIR-Ex4(9-39), that consists of a fluorescent Zn(2+) sensor and a truncated exendin 4 peptide for imaging insulin/Zn(2+) release in islet beta cells. In vitro, the conjugate bound to Zn(2+) with high affinity and displayed a robust fluorescence enhancement upon Zn(2+) chelation. When added to beta cells at submicromolar concentration, ZIMIR-Ex4(9-39) rapidly labeled cell surface in minutes to report the dynamics of insulin/Zn(2+) release with high spatiotemporal resolution. Future explorations of this approach may lead to probes for tracking beta cell function using different imaging modalities.