Shexiang Tongxin Dropping Pill Promotes Angiogenesis through VEGF/eNOS Signaling Pathway on Diabetic Coronary Microcirculation Dysfunction.

OBJECTIVE: To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD). METHODS: According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot. RESULTS: Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01). CONCLUSION: STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.

[Mechanism of Shexiang Tongxin Dropping Pills in treating diabetic cardiomyopathy based on network pharmacology and animal experiments].

This study aimed to explore the mechanism of Shexiang Tongxin Dropping Pills(STDP) in treating diabetic cardiomyopathy(DCM) based on network pharmacology, molecular docking, and animal experiments. BATMAN, TCMSP, and GeneCards were searched for the active ingredients and targets of STDP against DCM. STRING and Cytoscape were used to build the protein-protein interaction(PPI) network and "drug-active ingredient-target" network. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of the targets were carried out based on DAVID. The molecular docking of key receptor proteins with corresponding active ingredients was performed using AutoDock Vina. The rat model of DCM was established by a high-fat diet combined with intraperitoneal injection of streptozotocin. Rats were assigned into control, model, low-(20 mg·kg~(-1)) and high-dose(40 mg·kg~(-1)) STDP, and metformin(200 mg·kg~(-1)) groups. After 8 weeks of continuous administration, the cardiac function, myocardial pathological changes, and myocardial collagen fiber deposition of rats in each group were detected by echocardiography, hematoxylin-eosin(HE) staining, and Sirius red staining, respectively. The myocardial hypertrophy was detected by WGA staining. The expression levels of p38 mitogen-activated protein kinase(p38), phosphorylation-p38(p-p38), c-Jun N-terminal kinase(JNK), phosphorylation-JNK(p-JNK), caspase-3, and C-caspase-3 in the myocardial tissue of rats in each group were measured by Western blot. The network pharmacology predicted 199 active ingredients and 1 655 targets of STDP and 463 targets of DCM. One hundred and thirty-four potential targets of STDP for treating DCM were obtained, and the AGE-RAGE signaling pathway in diabetic complications was screened out. Molecular docking results showed that miltirone, dehydromiltirone, and tryptanthrin had strong binding affinity with RAGE. The results of animal experiments confirmed that STDP effectively protected the cardiac function of DCM rats. Compared with the DCM model group, the STDP groups showed significantly down-regulated protein levels of p-p38, p-JNK, and C-caspase-3. To sum up, STDP may protect the cardiac function of DCM rats by regulating the AGE-RAGE signaling pathway.

Single-cell bisulfite-free 5mC and 5hmC sequencing with high sensitivity and scalability.

Existing single-cell bisulfite-based DNA methylation analysis is limited by low DNA recovery, and the measurement of 5hmC at single-base resolution remains challenging. Here, we present a bisulfite-free single-cell whole-genome 5mC and 5hmC profiling technique, named Cabernet, which can characterize 5mC and 5hmC at single-base resolution with high genomic coverage. Cabernet utilizes Tn5 transposome for DNA fragmentation, which enables the discrimination between different alleles for measuring hemi-methylation status. Using Cabernet, we revealed the 5mC, hemi-5mC and 5hmC dynamics during early mouse embryo development, uncovering genomic regions exclusively governed by active or passive demethylation. We show that hemi-methylation status can be used to distinguish between pre- and post-replication cells, enabling more efficient cell grouping when integrated with 5mC profiles. The property of Tn5 naturally enables Cabernet to achieve high-throughput single-cell methylome profiling, where we probed mouse cortical neurons and embryonic day 7.5 (E7.5) embryos, and constructed the library for thousands of single cells at high efficiency, demonstrating its potential for analyzing complex tissues at substantially low cost. Together, we present a way of high-throughput methylome and hydroxymethylome detection at single-cell resolution, enabling efficient analysis of the epigenetic status of biological systems with complicated nature such as neurons and cancer cells.

A novel method for maize leaf disease classification using the RGB-D post-segmentation image data.

Maize (Zea mays L.) is one of the most important crops, influencing food production and even the whole industry. In recent years, global crop production has been facing great challenges from diseases. However, most of the traditional methods make it difficult to efficiently identify disease-related phenotypes in germplasm resources, especially in actual field environments. To overcome this limitation, our study aims to evaluate the potential of the multi-sensor synchronized RGB-D camera with depth information for maize leaf disease classification. We distinguished maize leaves from the background based on the RGB-D depth information to eliminate interference from complex field environments. Four deep learning models (i.e., Resnet50, MobilenetV2, Vgg16, and Efficientnet-B3) were used to classify three main types of maize diseases, i.e., the curvularia leaf spot [Curvularia lunata (Wakker) Boedijn], the small spot [Bipolaris maydis (Nishik.) Shoemaker], and the mixed spot diseases. We finally compared the pre-segmentation and post-segmentation results to test the robustness of the above models. Our main findings are: 1) The maize disease classification models based on the pre-segmentation image data performed slightly better than the ones based on the post-segmentation image data. 2) The pre-segmentation models overestimated the accuracy of disease classification due to the complexity of the background, but post-segmentation models focusing on leaf disease features provided more practical results with shorter prediction times. 3) Among the post-segmentation models, the Resnet50 and MobilenetV2 models showed similar accuracy and were better than the Vgg16 and Efficientnet-B3 models, and the MobilenetV2 model performed better than the other three models in terms of the size and the single image prediction time. Overall, this study provides a novel method for maize leaf disease classification using the post-segmentation image data from a multi-sensor synchronized RGB-D camera and offers the possibility of developing relevant portable devices.

Performance on inhibitory tasks does not relate to handedness in several small groups of Callitrichids.

Brain lateralization, a trait ubiquitous in vertebrates and invertebrates, refers to structural differences between the left and right sides of the brain or to the left and right sides controlling different functions or processing information in different ways. Many studies have looked into the advantages of lateralized brains and discovered that cerebral lateralization confers a fitness advantage. Enhancing cognitive ability has been proposed as one of the potential benefits of the lateralized brain, however, this has not been widely validated. In this study, we investigated the handedness of 34 subjects from four groups of Callitrichids, as well as their performance in two inhibitory control tasks (the revised A-not-B task and the cylinder task). The subjects had strong individual hand preferences, and only a few zoo-born individuals were ambidextrous. Sex and generation influence the strength of hand preference. In the cylinder task, the subjects showed differences between groups, and the performance of the second-generation was better than that of the first-generation. We found that neither the strength of hand preferences (ABS-HI) or direction of hand preferences (HI) was linked with success on the two inhibitory tasks. That is, we were unable to support the enhanced cognitive function hypothesis. We believe that individual ontogeny and the type of cognitive task have an impact on the support of this hypothesis. The advantages of lateralized brain may be reflected in tests that require multiple cognitive abilities.

Use of chemical labeling-assisted liquid chromatography-mass spectrometry for discovering derivatives of brassinosteroids.

Brassinosteroids (BRs) are plant steroid hormones that are involved in the regulation of plant growth and development as well as environmental adaptation. The discovery of new BR derivatives is beneficial to their biosynthesis and regulation mechanisms research. However, there are few reports on the methods for exploring new BRs, and the existing methods tend to lack coverage. In this work, we established a comprehensive, highly sensitive and selective structure-oriented method for the screening and structural identification of potential BRs in plants using chemical isotope labeling-assisted liquid chromatography-high resolution mass spectrometry (CL-LC-HRMS). The potential BRs were speculated according to the structural features of the reported BRs, and those speculated BRs containing cis-diol groups were labeled by isotope reagents of 2-methyl-4-phenylaminomethylphenylboronic acid (2-methyl-4-PAMBA) and 2-methyl-4-PAMBA-d5 to improve the sensitivity and selectivity of MS detection. In addition, the fragmentation of 2-methyl-4-PAMBA-labeled BRs via collision-induced dissociation (CID) led to the generation of reporter ions, which contributed to specific screening of potential BRs. In-depth structure of potential BRs was elucidated by analyzing multistage MS (MSn) fragmentation patterns. Using our proposed method, a total of 16 potential BRs were detected from plant samples including 5 new ones, of which one new BR derivative was identified as 2-deoxy-3-epi-6-deoxy-dolichosterone, and this new BR may be involved in the biosynthesis of BRs as precursor of 6-deoxo-dolichosterone. The method developed in this work is promising for screening and identifying new BR derivatives in plants, thereby supplementing the biosynthesis pathway of BRs.

Screening and Identification of Potential Abscisic Acid Catabolites by Chemical Labeling-Assisted Ultrahigh-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry.

In this study, a screening strategy was established based on ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry assisted by chemical isotope labeling (CIL-UPLC-HRMS) for screening and identifying abscisic acid (ABA) catabolites. Based on the structures of known ABA catabolites, this strategy first proposed the structures of catabolites to be discovered. Afterward, a pair of isotope reagents N,N-2-dimethylaminoethylamine (DMED) and d4-DMED were used as labeling reagents to label the carboxyl groups in ABA and its catabolites. Then, the mass-to-charge ratio (m/z) of DMED- and d4-DMED-labeled ABA catabolites was calculated based on the labeling schema. In light of the characteristic fragmentation patterns of the DMED-labeled standards of ABA and its catabolites, screening criteria were formulated. Using our strategy, ABA, t-ABA, and 18 ABA catabolites were identified from seven plant samples. Of the identified catabolites, 16 were known, and to our knowledge, 2 were previously unidentified. Our findings contribute to ABA catabolic network improvement.

Neophaseic acid catabolism in the 9'-hydroxylation pathway of abscisic acid in Arabidopsis thaliana.

Abscisic acid (ABA) hydroxylation is an important pathway for ABA inactivation and homeostasis maintenance. Here, we discover a new downstream catabolite of neophaseic acid (neoPA) in the ABA 9'-hydroxyl pathway and identify it as epi-neodihydrophaseic acid (epi-neoDPA) by comparing its accurate mass, retention time, and MSn spectra with those of our chemically synthesized epi-neoDPA. Analyses of Arabidopsis seed germination and ABA-related gene expression reveal that neoPA rather than epi-neoDPA possesses ABA-like hormonal activity. In vitro enzyme activity tests of prokaryotic recombinant protein reveal that NeoPAR1 (neoPA reductase 1) identified from Arabidopsis converts neoPA into epi-neoDPA. Site-directed mutation at Tyr163 in the conserved motif of NeoPAR1 abolishes the catalytic activity of NeoPAR1. Accelerated seed germination was observed in NeoPAR1 knockdown and knockout mutants, whereas retarded seed germination and the accumulation of epi-neoDPA and ABA were observed in NeoPAR1 overexpression lines, suggesting that NeoPAR1 is involved in seed germination and maintenance of ABA homeostasis.

Triple chemical derivatization strategy assisted liquid chromatography-mass spectrometry for determination of retinoic acids in human serum.

Retinoic acids (RAs), an important class of fatty acid derived from vitamin A, are closely associated with various human diseases including cancer. Hence, determination of endogenous RAs would help to uncover the mechanisms underlying RAs-related diseases. However, accurate quantification of RAs is still a challenge due to their high structure similarity, low abundance in biological samples and the lack of isotope internal standards (ISs). In this study, a liquid chromatography-mass spectrometry (LC-MS) method with high-sensitivity and high-throughput was developed to simultaneously determine 5 RAs (all-trans-retinoic acid, 13-cis-retinoic acid, 9,13-cis-retinoic acid, all-trans-4-oxoretinoic acid and 4-hydroxy-retinoic acid) in human serum. In the method, three derivatization reagents, N, N-dimethylethylenediamine (DMED), d4-N,N-dimethylethylenediamine (d4-DMED) and 13C2-N,N-dimethylethylenediamine (13C2-DMED), were used for triple chemical derivatization of RAs, thus the detection sensitivity and analysis throughput of endogenous RAs could be achieved. Benefiting from the developed strategy, the analysis throughput was enhanced and the detection sensitivity of RAs was increased by 14-398 folds. The limits of quantification (LOQs) of RAs were found to be between 8.4 and 130 pg/mL, which were better than previously reported methods. Good linearities of RAs were obtained with determination coefficient (R2) ranging from 0.9774 to 0.9999. The intra- and inter-day relative standard deviations (RSDs) were below 11.7% and 12.7%, respectively, indicating the acceptable reproducibility of the method. Using the developed method, we successfully quantified 4 RAs (all-trans-retinoic acid, 13-cis-retinoic acid, 9,13-cis-retinoic acid and all-trans-4-oxoretinoic acid) in health controls and cancer patient serum samples. Furthermore, t-test analysis showed that the concentration of three RAs (all-trans-retinoic acid, 13-cis-retinoic acid and all-trans-4-oxoretinoic acid) in cancer patient serum samples were significantly decreased compared with health controls, which indicated that RAs might play an important role in the formation and development of cancer.

The phytomelatonin receptor PMTR1 regulates seed development and germination by modulating abscisic acid homeostasis in Arabidopsis thaliana.

Melatonin is known to involve multiple physiological actions in plants. Herein, we found that exogenous melatonin inhibited the Arabidopsis seedling growth through the elevated abscisic acid (ABA) levels, and the elevated ABA was ascribed to the upregulation of 9-cis-epoxycarotenoid dioxygenase genes (NCEDs) in the ABA biosynthesis pathway. We also found that the overexpression lines of the melatonin receptor gene PMTR1 (also known as Cand2) yielded smaller seeds and germinated slower than the wild type, whereas PMTR1-knockout mutants produced larger seeds and germinated faster than the wild type. During the seed development, the accumulation peak of ABA was higher in the PMTR1-knockout mutant, while it was lower in the PMTR1-overexpression line than that in the wild type. In the dry seeds and imbibed seeds, the PMTR1-overexpression line accumulated higher ABA levels, while the PMTR1-knockout contained less ABA than the wild type. In summary, our findings suggest that PMTR1 is involved in ABA-mediated seed development and germination in Arabidopsis.

Highly sensitive analysis of cyanogenic glycosides in cold-pressed flaxseed oil by employing cigarette filter fiber-based SPE coupled with ultra-performance liquid chromatography-tandem mass spectrometry.

In this study, a highly sensitive method for analysis of 4 cyanogenic glycosides (CNGs) in cold-pressed flaxseed oil was developed by using cigarette filter fiber-based SPE and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The cold-pressed flaxseed oil was diluted with 5% (v/v) isopropanol/n-hexane solution and loaded to a cigarette filters fiber-based SPE column for CNG enrichment and purification. Under optimized conditions, four CNGs could be detected with limits of detection ranging from 1.3 to 4.4 pg/mL. The linear range was 0.05-50 ng/ml with a linear correlation coefficient (r) > 0.9935. CNG recovery ranged from 113% to 133%, and the relative standard deviation was between 0.8% and 20.5%. Finally, the proposed method was applied to the determination of CNGs in nine cold-pressed flaxseed oils.

Alternating Dual-Collision Energy Scanning Mass Spectrometry Approach: Discovery of Novel Microbial Bile-Acid Conjugates.

Bile acids (BAs) are a type of gut microbiota-host cometabolites with abundant structural diversity, and they play critical roles in maintaining host-microbiota homeostasis. In this study, we developed a new N-(4-aminomethylphenyl) pyridinium (AMPP) derivatization-assisted alternating dual-collision energy scanning mass spectrometry (AMPP-dual-CE MS) method for the profiling of BAs derived from host-gut microbiota cometabolism in mice. Using the proposed method, we discovered two new types of amino acid conjugations (alanine conjugation and proline conjugation) and acetyl conjugation with host BAs, for the first time, from mouse intestine contents and feces. Additionally, we also determined and identified nine new leucine- and phenylalanine-conjugated BAs. These findings broaden our knowledge of the composition of the BA pool and provide insight into the mechanism of host-gut microbiota cometabolism of BAs.

Cinnamoyl coA: NADP oxidoreductase-like 1 regulates abscisic acid response by modulating phaseic acid homeostasis in Arabidopsis thaliana.

Phaseic acid (PA), a main catabolite of abscisic acid (ABA), is structurally related to ABA and possesses ABA-like hormonal activity. However, the comprehensive metabolism pathway and roles of PA are not well understood. Here, using homologous alignment and expression pattern analysis, we identified in Arabidopsis the previously named CRL1 (Cinnamoyl coA: NADP oxidoreductase-like 1) as a PA reductase that catalyses PA to dihydrophaseic acid. The function of CRL1 and the potential role of PA were studied in transgenic CRL1 plants. Overexpression of CRL1 resulted in decreased ABA sensitivity in seed germination and attenuated drought tolerance. In contrast, increased ABA sensitivity and elevated drought tolerance was observed in down-regulated and loss-of-function crl1 mutants. Tyr162 in the conserved motif is the key residue in CRL1 to catalyse PA. Accelerated seed germination and earlier flowering phenotype were also observed in overexpressing lines, while retarded seed germination and delayed flowering occurred in crl1 mutants which accumulated more PA, but less dihydrophaseic acid than the wild type. This study demonstrates that PA plays diverse functions in drought tolerance, seed germination and flowering in an ABA-like manner, which may increase the adaptive plasticity of plants.

[Shexiang Tongxin Dropping Pills improve cardiac function in type 2 diabetic rats by promoting angiogenesis].

This study aims to investigate the effect of Shexiang Tongxin Dropping Pills(STDP) on angiogenesis in type 2 diabetic rats. Thirty-two healthy male SD rats were randomized into a control group(n=6) and a type 2 diabetes mellitus(T2 D) group(n=26). The T2 DM rat model was established with a high-fat diet combined with intraperitoneal injection of streptozotocin(STZ). The model rats were randomized into a model group, a metformin group(200 mg·kg~(-1)·d~(-1)), a high-dose STDP group(40 mg·kg~(-1)·d~(-1)), and a low-dose STDP group(20 mg·kg~(-1)·d~(-1)). The corresponding agents were administered continuously for 8 weeks. The cardiac function indexes were detected by ultrasound at the experiment endpoint, and the myocardial pathological changes were observed via hematoxylin-eosin(HE) staining. The myocardial collagen fiber deposition was detected by sirius red staining, the myocardial microvascular density by immunohistochemistry, and the myocardial hypertrophy by immunofluorescence assay. Western blot was employed to measure the protein levels of vascular endothelial growth factor(VEGF), phosphorylated vascular endothelial growth factor receptor 2(p-VEGFR2), angiogenin-1(Ang1), and TEK tyrosine kinase endothelial(Tie2) in the myocardial tissue. Compared with the model group, STDP improved the left ventricular ejection fraction(EF) and fractional shortening(FS)(P<0.05), alleivated the arrangement disorder of myocardial cells and local myocardial fiber rupture. Sirius red staining showed that STDP, especially the high-dose group(P<0.01), repaired the deposition of myocardial collagen fibers in the model group. The results of immunohistochemistry showed that the cluster of differentiation 31(CD31) expression in myocardial tissue of the STDP groups was higher than that of the model group(P<0.01). The immunofluorescence results showed that STDP mitigated the hypertrophy of myocardial cells(P<0.01). Furthermore, STDP up-regulated the protein levels of VEGF, p-VEGFR2, Angl, and Tie2 compared with the model group(P<0.01). In conclusion, STDP can effectively promote angiogenesis and improve cardiac function in type 2 diabetic rats by up-regulating the expression of VEGF, p-VEGFR2, Ang1, and Tie2.

Stability and optimal control strategies for a novel epidemic model of COVID-19.

In this paper, a novel two-stage epidemic model with a dynamic control strategy is proposed to describe the spread of Corona Virus Disease 2019 (COVID-19) in China. Combined with local epidemic control policies, an epidemic model with a traceability process is established. We aim to investigate the appropriate control strategies to minimize the control cost and ensure the normal operation of society under the premise of containing the epidemic. This work mainly includes: (i) propose the concept about the first and the second waves of COVID-19, as well as study the case data and regularity of four cities; (ii) derive the existence and stability of the equilibrium, the parameter sensitivity of the model, and the existence of the optimal control strategy; (iii) carry out the numerical simulation associated with the theoretical results and construct a dynamic control strategy and verify its feasibility.

Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines.

SARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B.1.351), of the plasma and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine), ZF2001 (RBD-subunit vaccine) and natural infection. Among 86 potent NAbs identified by high-throughput single-cell VDJ sequencing of peripheral blood mononuclear cells from vaccinees and convalescents, near half anti-RBD NAbs showed major neutralization reductions against the K417N/E484K/N501Y mutation combination, with E484K being the dominant cause. VH3-53/VH3-66 recurrent antibodies respond differently to RBD variants, and K417N compromises the majority of neutralizing activity through reduced polar contacts with complementarity determining regions. In contrast, the 242-244 deletion (242-244Δ) would abolish most neutralization activity of anti-NTD NAbs by interrupting the conformation of NTD antigenic supersite, indicating a much less diversity of anti-NTD NAbs than anti-RBD NAbs. Plasma of convalescents and CoronaVac vaccinees displayed comparable neutralization reductions against pseudo- and authentic 501Y.V2 variants, mainly caused by E484K/N501Y and 242-244Δ, with the effects being additive. Importantly, RBD-subunit vaccinees exhibit markedly higher tolerance to 501Y.V2 than convalescents, since the elicited anti-RBD NAbs display a high diversity and are unaffected by NTD mutations. Moreover, an extended gap between the third and second doses of ZF2001 leads to better neutralizing activity and tolerance to 501Y.V2 than the standard three-dose administration. Together, these results suggest that the deployment of RBD-vaccines, through a third-dose boost, may be ideal for combating SARS-CoV-2 variants when necessary, especially for those carrying mutations that disrupt the NTD supersite.

Integrated Traditional Chinese and Western medicine for ulcerative colitis with diabetes: A protocol for systematic review and meta-analysis.

BACKGROUND: This study aimed to access the efficacy and safety of integrated Traditional Chinese and Western medicine treatment for patients with ulcerative colitis (UC) combined diabetes. METHODS: This protocol adheres to the preferred reporting items for systematic reviews and meta-analysis protocol statement. We plan to search 8 electronic databases to identify qualifying studies published from database inception until December 1, 2020. The software of EndNote reference manager (X9) will be used to study selection. A pre-developed standardized data collection form will be used to extract from all eligible studies. For included studies, the quality will be assessed by Cochrane Risk of bias tool. The RevMan 5.3 software (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) developed by the Cochrane Collaboration will be used for all statistical analysis. If possible, meta-analysis will be undertaken for each of the outcomes. For continuous variable data, we will used mean differences with 95% confidence intervals (CIs) as summary statistics. For dichotomous variable data, we will calculate Mantel-Haenszel odds ratio with 95% CIs as summary statistics from the numbers of events in control and intervention groups. We will consider a result to be statistically significant if P < .05. If outcomes cannot be meta-analyzed, we will performer a descriptive analysis. RESULTS: This study will be performed to test the efficacy and safety of integrated Traditional Chinese and Western medicine treatment for patients with UC combined diabetes. CONCLUSION: The results of our study will be published in a peer-reviewed journals, and we will promotion results in domestic and foreign conferences. REGISTRATION NUMBER: INPLASY2020120087. ETHICS AND DISSEMINATION: As a systematic review and meta-analysis which based on previously published literature, ethical approval, and informed consent from patients are not required.

Boron Isotope Tag-Assisted Ultrahigh-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry for Discovery and Annotation of cis-Diol-Containing Metabolites.

cis-Diol-containing metabolites are widely distributed in living organisms, and they participate in the regulation of various important biological activities. The profiling of cis-diol-containing metabolites could help us in fully understanding their functions. In this work, based on the characteristic isotope pattern of boron, we employed a boronic acid reagent as the isotope tag to establish a sensitive and selective liquid chromatography-high-resolution mass spectrometry method for the screening and annotation of cis-diol-containing metabolites in biological samples. Boronic acid reagent 2-methyl-4-phenylaminomethylphenylboronic acid was used to label the cis-diol-containing metabolites in biological samples to improve the selectivity and MS sensitivity of cis-diol-containing metabolites. Based on the characteristic 0.996 Da mass difference of precursor ions and the peak intensity ratio of 1:4 originating from 10B and 11B natural isotopes, the potential cis-diol-containing metabolites were rapidly screened from biological samples. Potential cis-diol-containing metabolites were annotated by database searching and analysis of fragmentation patterns obtained by multistage MS (MSn) via collision-induced dissociation. Importantly, the cis-diol position could be readily resolved by the MS3 spectrum. With this method, a total of 45 cis-diol-containing metabolites were discovered in rice, including monoglycerides, polyhydroxy fatty acids, fatty alcohols, and so forth. Furthermore, the established method showed superiority in avoiding false-positive results in profiling cis-diol-containing metabolites.

Monkeys fight more in polluted air.

Air pollution is a global environmental problem, and its effects on human behavior, psychology, and health have been well studied. However, very few studies were done on if and how air pollution affects animal behavior, for example, social conflict. Many physiological and psychological evidences suggest a possible positive relationship between air pollution and animal social conflict, thus we established a multiple linear regression model using a captive monkey group to explore if monkeys behave more aggressively in polluted air. Our results confirmed that daily social fighting behaviors occurred more when air is polluted. Temperature has a nonlinear effect on monkey social conflict, with a fighting peak at 25-29 °C. To our knowledge, this is the first report that animal social conflict, like humans, is also affected by air pollution and temperature.