CBX7 promotes choroidal neovascularization by activating the HIF-1α/VEGF pathway in choroidal vascular endothelial cells.

Vascular endothelial growth factor (VEGF) signaling is crucial for choroidal neovascularization (CNV), a major pathological feature of neovascular age-related macular degeneration (nAMD). Gene transcription of VEGF is mainly regulated by hypoxia-inducible factor 1-alpha (HIF-1α). The chromobox (CBX) family polycomb protein (Pc) subgroup includes CBX2, CBX4, CBX6, CBX7, and CBX8. CBX4 enhances hypoxia-induced VEGF expression and angiogenesis in hepatocellular carcinoma (HCC) cells by increasing HIF-1α's transcriptional activity. The objective of the study was to examine the functions of members of the CBX family Pc subgroup in choroidal vascular endothelial cells (CVECs) during CNV. CBX4 and CBX7 expression was up-regulated in hypoxic human choroidal vascular endothelial cells (HCVECs). In HCVECs, CBX7 facilitated HIF-1α transcription and expression, while CBX4 did not. In HCVECs, CBX7 stimulated HIF-1α's nuclear translocation and transcriptional activity, which in turn stimulated VEGF transcription and expression. The CBX7/HIF-1α/VEGF pathway promoted the migration, proliferation, and tube formation of HCVECs. The CBX7/HIF-1α/VEGF pathway was up-regulated in CVECs and in the mouse model with laser-induced CNV. Mouse CNV was lessened by the blockade of CBX7 through the down-regulation of HIF-1α/VEGF. In conclusion, CBX7 enhanced pro-angiogenic behaviors of hypoxic CVECs by up-regulating the HIF-1α/VEGF pathway, which contributing to the formation of mouse laser-induced CNV.

XGBoost algorithm assisted multi-component quantitative analysis with Raman spectroscopy.

To improve prediction performance and reduce artifacts in Raman spectra, we developed an eXtreme Gradient Boosting (XGBoost) preprocessing method to preprocess the Raman spectra of glucose, glycerol and ethanol mixtures. To ensure the robustness and reliability of the XGBoost preprocessing method, an X-LR model (which combined XGBoost preprocessing and a linear regression (LR) model) and a X-MLP model (which combined XGBoost preprocessing and a multilayer perceptron (MLP) model) were developed. These two models were used to quantitatively analyze the concentrations of glucose, glycerol and ethanol in the Raman spectra of mixed solutions. The proportion map of hyperparameters was firstly used to narrow down the search range of hyperparameters in the X-LR and the X-MLP models. Then the correlation coefficients (R2), root mean square of calibration (RMSEC), and root mean square error of prediction (RMSEP) were used to evaluate the models' performance. Experimental results indicated that the XGBoost preprocessing method achieved higher accuracy and generalization capability, with better performance than those of other preprocessing methods for both LR and MLP models.

Safety profiles of doxycycline, minocycline, and tigecycline in pediatric patients: a real-world pharmacovigilance analysis based on the FAERS database.

Introduction: Recently, the rise of antibiotic resistance has prompted a reconsideration of tetracyclines. However, existing studies are inadequate in assessing the pediatric safety of this class of antibiotics. To address the gap, our study aims to comprehensively assess the safety of tetracyclines in children. Methods: Adverse event (AE) reports from January 2005 to September 2023 were obtained from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, and reporting odds ratio (ROR) was performed to identify potential risk signals in children under 18 years old who were administered any of the three tetracyclines: doxycycline, minocycline, and tigecycline. Results: A total of 1903 AE cases were included in our study: 782 for doxycycline, 981 for minocycline, and 140 for tigecycline. Doxycycline and tigecycline were predominantly associated with "general disorders and administration site conditions" and "gastrointestinal disorders," while minocycline was more frequently linked to "skin and subcutaneous tissue disorders" and "gastrointestinal disorders." Psychiatric risks predominantly included depression, suicidal ideation, and suicide attempt. In the category of skin and subcutaneous tissues, 30.88% of the minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) cases resulted in death, alongside a high occurrence of co-occurring AEs such as multiple organ dysfunction syndrome, Type 1 Diabetes Mellitus (T1DM), and autoimmune thyroiditis. As for the endocrine system, both doxycycline and minocycline were found to potentially increase the risk of thyroid dysfunction. For children under the age of 8, doxycycline was associated with tooth discoloration (N = 7, ROR = 20.11%, 95% CI: 9.48-42.67), although it remained unclear whether the discoloration was permanent. Conclusion: Our findings indicated that for pediatric patients, the majority of results were in line with the prescribing information and previous studies, and minocycline tended to cause more frequent and severe AEs than doxycycline. However, it is noteworthy that exceptions were found for psychiatric disorders and thyroid dysfunction associated with doxycycline, which are not mentioned in its FDA prescribing information. Additionally, further safety studies on tigecycline are still needed for children. When prescribing tetracyclines to pediatric patients, a careful risk-benefit assessment is crucial.

Eurasian otters prefer to prey on religious released non-native fish on the Qinghai-Tibetan Plateau.

Religious wildlife release is prevalent worldwide, especially in Asia countries. It is one of the anthropogenic pathways to cause biological invasions. Religious fish release is common on the Qinghai-Tibetan Plateau, yet few studies have assessed the influences of religious fish release on local species. In Yushu, a city on the Qinghai-Tibetan Plateau, we interviewed local people, conducted fish trap surveys in local rivers, and examined the diet of Eurasian otters Lutra lutra using a fecal DNA metabarcoding approach. We found that fish release started at least in 1980-1990s in Yushu. Tibetan residents released fish in large amounts and released fish were usually exotic commercial fish purchased from market. Despite such long-term and intensive fish release activities, released fish were few in local rivers. On the other hand, Eurasian otters mainly prey on fish and released fish accounted for ~20% of relative read abundance of prey DNA in otters' diet, indicating their high preference on released fish. Our study suggested that religious fish release may provide additional food resources for otters, whereas otters, as a top predator in local rivers, may deplete non-native fish once they were released and, therefore, reduce the probability of colonization of released fish, although further studies are required to assess otters' impact. Our study revealed otters' diet in Yushu, providing basic information for local otter management and conservation. Furthermore, it represents a case showing that native predators prey on religious released animals, implying a probable direction for controlling invasive species through native predator conservation.

Characterization of biomass burning tracers in particulate matter at 12 sites in China: Significant increase of coal combustion emitted levoglucosan in northern China during winter.

Biomass burning (BB) is the largest contributor to carbonaceous aerosols globally. Specific organic tracers can track BB particles and identify BB types. At present, there is limited information on the composition of BB tracers on a continental scale. In this study, we conducted year-round sampling of particulate matter (PM) at 12 sites in China. Nine BB tracers were measured in PM with aerodynamic diameters <1.1 µm (PM<1.1), in the range of 1.1-3.3 µm (PM1.1-3.3), and > 3.3 µm (PM>3.3). The annual average concentration of these nine BB tracers (∑9 BB tracers) in the total PM was 366 ng m-3 with the majority of levoglucosan (66 %). The concentration of ∑9 BB tracers was higher in northern China than in southern China, especially in winter. ∑9 BB tracers were most enriched in PM<1.1 (50-61 % in mass), followed by PM1.1-3.3 and PM>3.3. The highest concentrations of ∑9 BB tracers were observed in winter, while satellite-recorded fire spots were intensive in autumn and spring. The mismatch of seasonal trends between them indicated that the high levels of BB tracers in winter was not due to open BB. The composition of 4-hydroxybenzoic acid, syringic acid and vanillic acid suggested that the burning of crop residues and softwoods were the major BB types in China. The ratio of levoglucosan to mannosan could neither identify the major BB types in China nor distinguish between BB and coal combustion. Correlation analysis and the PMF model demonstrated that non-BB sources contributed 7 %-58 % to levoglucosan at the 12 sites, with coal combustion being the predominant non-BB source in China, especially in northern urban sites during winter. Our findings suggest that caution should be taken in application of these organic tracers to identify BB types and estimate BB aerosols.

High-sensitivity narrow­band T-shaped cantilever Fabry-perot acoustic sensor for photoacoustic spectroscopy.

Photoacoustic spectroscopy (PAS) has been rapidly developed and applied to different detection scenarios. The acoustic pressure detection is an important part in the PAS system. In this paper, an ultrahigh sensitivity Fabry-Perot acoustic sensor with a T-shaped cantilever was proposed. To achieve the best acoustic pressure effect, the dimension of the cantilever structure was designed and optimized by finite element analysis using COMSOL Multiphysics. Simulation results showed that the sensitivity of such T-shaped cantilever was 1.5 times higher than that based on a rectangular cantilever, and the resonance frequency of T-shaped cantilever were able to modulate from 800 Hz to 1500 Hz by adjusting the multi-parameter characteristics. Experimental sensing results showed that the resonance frequency of T-shaped Fabry-Perot acoustic sensor was 1080 Hz, yielding a high sensitivity of 1.428 µm/Pa, with a signal-to-noise ratio (SNR) of 84.8 dB and a detectable pressure limit of 1.9 µPa/Hz1/2@1 kHz. We successfully used such acoustic sensor to measure acetylene (C2H2) concentration in the PAS. The sensitivity of PAS for C2H2 gas was 3.22 pm/ppm with a concentration range of 50 ppm ∼100 ppm, and the minimum detection limit was 24.91ppb.

Comparison of the therapeutic effects of lens capsular flap transplantation and autologous retinal transplantation in the management of refractory macular holes.

PURPOSE: To report the comparison of the therapeutic effects of lens capsular flap transplantation (LCT) and autologous retinal transplantation (ART) in refractory macular hole (MH) treatment. METHODS: Thirty-one patients (31 eyes) with refractory MH were retrospectively reviewed. The patients were divided into two groups based on the surgical procedures: the LCT group (13 eyes) and the ART group (18 eyes). Patients were monitored for a minimum of 6 months. Best corrected visual acuity (BCVA), hole closure rate, postoperative central foveolar thickness (CFT), and some complications (e.g. graft loss or dislocation, postoperative retinal detachment, or postoperatively elevated intraocular pressure) were the primary outcome measures. RESULTS: The mean preoperative MH diameter was 1104 ± 287 µm in the LCT group and 1066 ± 297 µm in the ART group (t = 0.353, P = 0.727). The MH was closed in 12 patients (92.3%) of the LCT group and 17 patients (94.4%) of the ART group (χ2 = 0.057, P = 0.811); the MHs of 10 patients (76.9%) in the LCT group and 11 patients (61.1%) in the ART group were completely closed (χ2 = 0.864, P = 0.353). The BCVA improved from 2.3 ± 1.0 logMAR preoperatively to 1.3 ± 0.9 logMAR postoperatively in the LCT group and 2.3 ± 0.9 logMAR preoperatively to 1.0 ± 0.6 logMAR postoperatively in the ART group (postoperative BCVA vs preoperative BCVA in the LCT group: t = 4.374, P = 0.001; postoperative BCVA vs preoperative BCVA in the ART group: t = 5.899, P = 0.000018). The visual improvement was 1.3 ± 0.9 logMAR in the ART group and 1.0 ± 0.8 logMAR in the LCT group (t = - 1.033, P = 0.310). The postoperative CFT was 139.7 ± 48.3 µm in the LCT and 199.2 ± 25.1 µm in the ART group (t = - 4.062, P = 0.001). Graft dislocation emerged in 2 patients (15.4%) in the LCT group and 1 patient (5.6%) in the ART group. CONCLUSIONS: Applications of LCT and ART may both enhance anatomical and visual outcomes in refractory MH cases. The ART group exhibited a more optimal postoperative CFT than the LCT group one.

Celastrol Regulates the Hsp90-NLRP3 Interaction to Alleviate Rheumatoid Arthritis.

Previous studies have verified that celastrol (Cel) protects against rheumatoid arthritis (RA) by inhibiting the NLRP3 inflammasome signaling pathway, but the molecular mechanism by which Cel regulates NLRP3 has not been clarified. This study explored the specific mechanisms of Cel in vitro and in vivo. A type II collagen-induced arthritis (CIA) mouse model was used to study the antiarthritic activity of Cel; analysis of paw swelling, determination of the arthritis score, and pathological examinations were performed. The antiproliferative and antimigratory effects of Cel on TNF-α induced fibroblast-like synoviocytes (FLSs) were tested. Proinflammatory factors were evaluated using enzyme-linked immunosorbent assay (ELISA). The expression of NF-κB/NLRP3 pathway components was determined by western blotting and immunofluorescence staining in vitro and in vivo. The putative binding sites between Cel and Hsp90 were predicted through molecular docking, and the binding interactions were determined using the Octet RED96 system and coimmunoprecipitation. Cel decreased arthritis severity and reduced TNF-α-induced FLSs migration and proliferation. Additionally, Cel inhibited NF-κB/NLRP3 signaling pathway activation, reactive oxygen species (ROS) production, and proinflammatory cytokine secretion. Furthermore, Cel interacted directly with Hsp90 and blocked the interaction between Hsp90 and NLRP3 in FLSs. Our findings revealed that Cel regulates NLRP3 inflammasome signaling pathways both in vivo and in vitro. These effects are induced through FLSs inhibition of the proliferation and migration by blocking the interaction between Hsp90 and NLRP3.

Tocilizumab attenuates choroidal neovascularization by regulating macrophage polarization through the IL-6R/STAT3/VEGF pathway.

Globally, age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment. Up to 80% of severe vision loss is caused by AMD, which is characterized by the development of choroidal neovascularization (CNV). Uncertainty exists regarding the precise pathophysiological mechanisms of CNV. It has been suggested that the interleukin (IL) IL-6/IL-6R signaling pathway is crucial in the progression of CNV. Tocilizumab (TCZ), a monoclonal antibody, binds to soluble and membrane-bound IL-6R and competitively inhibits IL-6 downstream signaling. Previous research has demonstrated that TCZ promotes several roles related to inflammation and neovascularization. However, the effects of TCZ on CNV and the underlying mechanism are still unknown. This study found that TCZ administration decreased the area and leakage of CNV lesions in the mice model of laser-induced CNV. Additionally, results demonstrated that TCZ promotes the expression of iNOS, CCL-3, CCL-5, TNF-α and inhibits the expression of Arg-1, IL-10, YM-1 and CD206. Furthermore, TCZ treatment inhibited the signal transducer and activator of transcription (STAT) STAT3/vascular endothelial growth factor (VEGF) pathway, which was activated after CNV formation. Colivelin, a STAT3 agonist, reversed the inhibitory effects of TCZ on CNV formation and macrophage polarization. In a mouse model of laser-induced CNV, our findings demonstrated that TCZ attenuated CNV formation and inhibited the leakage of CNV lesions by regulating macrophage polarization via inhibiting the STAT3/VEGF axis. TCZ is the potential therapeutic strategy for CNV.

The Contributions of Thrombospondin-1 to Epilepsy Formation.

Epilepsy is a neural network disorder caused by uncontrolled neuronal hyperexcitability induced by an imbalance between excitatory and inhibitory networks. Abnormal synaptogenesis plays a vital role in the formation of overexcited networks. Recent evidence has confirmed that thrombospondin-1 (TSP-1), mainly secreted by astrocytes, is a critical cytokine that regulates synaptogenesis during epileptogenesis. Furthermore, numerous studies have reported that TSP-1 is also involved in other processes, such as angiogenesis, neuroinflammation, and regulation of Ca2+ homeostasis, which are closely associated with the occurrence and development of epilepsy. In this review, we summarize the potential contributions of TSP-1 to epilepsy development.

High sensitivity and ultra-low concentration range photoacoustic spectroscopy based on trapezoid compound ellipsoid resonant photoacoustic cell and partial least square.

A high sensitivity and ultra-low concentration range photoacoustic spectroscopy (PAS) gas detection system, which was based on a novel trapezoid compound ellipsoid resonant photoacoustic cell (TCER-PAC) and partial least square (PLS), was proposed to detect acetylene (C2H2) gas. In the concentration range of 0.5 ppm ∼ 10.0 ppm, the limit of detection (LOD) values of TCER-PAC-based PAS system without data processing was 66.4 ppb, which was lower than that of the traditional trapezoid compound cylindrical resonant photoacoustic cell (TCCR-PAC). The experimental results indicated that the TCER-PAC had higher sensitivity than of TCCR-PAC. Within the concentration range of 12.5 ppb ∼ 125.0 ppb, the LOD and limit of quantification (LOQ) of TCER-PAC-based PAS system combined with PLS regression algorithm were 1.1 ppb and 3.7 ppb, respectively. The results showed that higher detection sensitivity and lower LOD were obtained by PAS system with TCER-PAC and PLS than that of TCCR-PAC-based PAS system.

Low but highly geographically structured genomic diversity of East Asian Eurasian otters and its conservation implications.

Populations of Eurasian otters Lutra lutra, one of the most widely distributed apex predators in Eurasia, have been depleted mainly since the 1950s. However, a lack of information about their genomic diversity and how they are organized geographically in East Asia severely impedes our ability to monitor and conserve them in particular management units. Here, we re-sequenced and analyzed 20 otter genomes spanning continental East Asia, including a population at Kinmen, a small island off the Fujian coast, China. The otters form three genetic clusters (one of L. l. lutra in the north and two of L. l. chinensis in the south), which have diverged in the Holocene. These three clusters should be recognized as three conservation management units to monitor and manage independently. The heterozygosity of the East Asian otters is as low as that of the threatened carnivores sequenced. Historical effective population size trajectories inferred from genomic variations suggest that their low genomic diversity could be partially attributed to changes in the climate since the mid-Pleistocene and anthropogenic intervention since the Holocene. However, no evidence of genetic erosion, mutation load, or high level of inbreeding was detected in the presumably isolated Kinmen Island population. Any future in situ conservation efforts should consider this information for the conservation management units.

PD-1/PD-L1 inhibitors-associated cardiac adverse events: a retrospective and real-world study based on the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors have reformed the treatment landscape for various malignancies and improved prognosis of patients. However, they also lead to events that although rare may prove to be fatal. RESEARCH DESIGN AND METHODS: Data from July 2014 to June 2022 based on FDA Adverse Event Reporting System (FAERS) were analyzed. The signal index reporting odds ratio (ROR) was used to evaluate the correlation between cardiac AEs and given medications. The indications and the median time to onset (TTO) of different PD-1/PD-L1 inhibitors were compared. RESULTS: Cardiac AEs are rare but may be fatal with particular profiles in primary tumor, onset time, and especially gender. We identified 11,538 reports that were related to cardiotoxicity of PD-1/PD-L1 inhibitors, in which 178 different preferred terms (PTs) were distinguished, and nivolumab reported the most PTs with signal. All targeted medications showed signals in myocardial disorders and pericardial disorders, which tend to occur in the first 1-2 months. Non-small cell neoplasm was the top and common indication during anti-PD-1 or anti-PD-L1 therapy with cardiotoxicity. CONCLUSIONS: This study could help early diagnosis and surveillance of ICIs-related cardiotoxicity.

Photoacoustic Spectroscopy Gas Detection Technology Research Progress.

Photoacoustic spectroscopy (PAS) can be utilized as an ultrasensitive gas detection method. The basic principles of gas detection using PAS are discussed in this paper. First, the basic instrumentation for a PAS gas detection system is introduced focusing on the photoacoustic cell. The discussion includes non-resonant photoacoustic cells and the different types of resonant photoacoustic cells, including the longitudinal photoacoustic cell, the Helmholtz photoacoustic cell, the T-type photoacoustic cell, and the high-frequency resonant photoacoustic cell. The basic working principles of each of these, cells as well as the advantages and disadvantages of photoacoustic cells are discussed, and the development of newer types of photoacoustic cells in recent years is outlined in detail. This review provides detailed reference information and guidance for interested researchers who would like to design and build advanced photoacoustic cells for gas detection.

Inhibition of PTEN-induced kinase 1 autophosphorylation may assist in preventing epileptogenesis induced by pentylenetetrazol.

PTEN-induced kinase 1 (PINK1) autophosphorylation-triggered mitophagy is the main mitophagic pathway in the nervous system. Moreover, multiple studies have confirmed that mitophagy is closely related to the occurrence and development of epilepsy. Therefore, we speculated that the PINK1 autophosphorylation may be involved in epileptogenesis by mediating mitophagic pathway. This study aimed to explore the contribution of activated PINK1 to epileptogenesis induced by pentylenetetrazol (PTZ) in Sprague‒Dawley rats. During PTZ-induced epileptogenesis, the levels of phosphorylated PINK1 were increased, accompanied by elevated mitophagy, mitochondria oxidative stress and neuronal damage. After microRNA intervention targeting translocase outer mitochondrial membrane 7 (TOM7) or overlapping with the m-AAA protease 1 homolog (OMA1), the levels of PINK1 phosphorylation, mitophagy, mitochondrial oxidative stress, neuronal injury were observed in the rats with induced epileptogenesis. Furthermore, inhibiting of the expression of TOM7, a positive regulator of PINK1 autophosphorylation, reversed the increase in PINK1 phosphorylation and alleviated mitophagy, neuronal injury, thereby preventing epileptogenesis. In contrast, reducing the levels of OMA1, a negative regulator of PINK1 autophosphorylation, led to increased phosphorylation of PINK1, accompanied by aggravated neuronal injury and ultimately, epileptogenesis. This study confirmed the contribution of activated PINK1 to PTZ-induced epileptogenesis and suggested that the inhibition of PINK1 autophosphorylation may assist in preventing epileptogenesis.

Complete Genome Sequence and Pan-Genome Analysis of Shewanella oncorhynchi Z-P2, a Siderophore Putrebactin-Producing Bacterium.

In this study, we reported the complete genome sequence of Shewanella oncorhynchi for the first time. S. oncorhynchi Z-P2 is a bacterium that produces the siderophore putrebactin. Its genome consists of a circular chromosome of 5,034,612 bp with a G + C content of 45.4%. A total of 4544 protein-coding genes, 109 tRNAs and 31 rRNAs were annotated by the RAST. Five non-ribosomal peptide synthetase (NRPS) and polyketide synthetase (PKS) gene clusters were identified by the antiSMASH analysis. The pan-genome analysis of Z-P2 and 10 Shewanella putrefaciens revealed 9228 pan-gene clusters and 2681 core gene clusters, with Z-P2 having 618 unique gene clusters. Additionally, the gene cluster involved in putrebactin biosynthesis in Z-P2 was annotated, and the mechanism of putrebactin biosynthesis was analyzed. The putrebactin produced by Z-P2 was detected using UPLC-MS analysis, with an [M + H]+ molecular ion at m/z 373.21. These findings provide valuable support for further research on the genetic engineering of putrebactin biosynthetic genes of Z-P2 and their potential applications.

Neutrophil extracellular traps boost laser-induced mouse choroidal neovascularization through the activation of the choroidal endothelial cell TLR4/HIF-1α pathway.

Choroidal neovascularization (CNV) is characterized by the infiltration of immune cells, particularly neutrophils. Neutrophil extracellular trap (NET) facilitates the angiogenesis of pulmonary endothelial cells via activating Toll-like receptor 4 (TLR4). TLR4 promotes the expression of transcription factor hypoxia inducible factor-1α (HIF-1α), which promotes inflammation and angiogenesis via the up-regulation of metalloproteinase-9 (MMP-9) and interleukin-1ß (IL-1ß). In the present study, we aimed to identify the formation of NET and its role in CNV. Our results showed that NET levels were increased in a mouse laser-induced CNV model via oxidative stress, whereas the inhibition of NET alleviated CNV. In vitro, NET activated the TLR4/HIF-1α pathway in human choroidal endothelial cells (HCECs). Additionally, NET increased the transcription and expression of MMP-9 and IL-1ß in HCECs via activating the TLR4/HIF-1α pathway. Meanwhile, NET promoted the inflammatory response accompanied by the proliferation, migration and tube formation of HCECs in a MMP-9- and IL-1ß-dependent manner. In conclusion, NET was up-regulated in CNV and promoted the formation of CNV via activating the TLR4/HIF-1α pathway in choroidal endothelial cells. Our data uncovered the novel role of NET in promoting the formation of CNV. The underlying mechanism of NET could be targeted to delay the process of CNV.

High-precision prediction of blood glucose concentration utilizing Fourier transform Raman spectroscopy and an ensemble machine learning algorithm.

Raman spectroscopy has gained popularity in analyzing blood glucose levels due to its non-invasive identification and minimal interference from water. However, the challenge lies in how to accurately predict blood glucose concentrations in human blood using Raman spectroscopy. This paper researches a novel integrated machine learning algorithm called Bagging-ABC-ELM. The optimal input weights and biases of extreme learning machine (ELM) model are obtained by artificial bee colony (ABC) algorithm. The bagging algorithm is used to obtain a better the stability of the model and higher performance than ELM algorithm. The results show that the mean value of coefficient of determination is 0.9928, and root mean square error is 0.1928. Compared to other regression models, the Bagging-ABC-ELM model exhibited superior prediction accuracy, robustness, and generalization capability. The Bagging-ABC-ELM model presents a promising alternative for analyzing blood glucose levels in clinical and research settings.

[Herbal-moxa plaster for diarrhea type irritable bowel syndrome of spleen and kidney yang deficiency: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between herbal-moxa plaster and moxa-box moxibustion for diarrhea type irritable bowel syndrome (IBS-D) of spleen and kidney yang deficiency. METHODS: Eighty patients with IBS-D of spleen and kidney yang deficiency were randomly divided into a herbal-moxa plaster group and a moxa-box moxibustion group, 40 cases in each group. The patients in the two groups were treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 24+), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Yinlingquan (SP 9), and Taixi (KI 3), etc. In addition, the patients in the herbal-moxa plaster group were treated with herbal-moxa plaster (Wenyang Fuzheng ointment, composed of prepared monkshood, prepared evodia rutaecarpa, dried ginger, cinnamon, etc.) at Shenque (CV 8), Guanyuan (CV 4), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Shenshu (BL 23) and Shangjuxu (ST 37); the patients in the moxa-box moxibustion group were treated with moxa-box moxibustion at the same acupoints as the herbal-moxa plaster group. The acupuncture-moxibustion treatment was provided once every other day for 4 weeks (14 treatments). Before and after treatment, the scores of clinical symptom of TCM, irritable bowel syndrome (IBS) symptom severity scale (IBS-SSS) and IBS quality of life scale (IBS-QOL) were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: Compared with those before treatment, each item scores and total scores of clinical symptom of TCM, and IBS-SSS scores in the two groups were reduced after treatment (P<0.05). The abdominal bloating score, stool frequency score and total score of clinical symptom of TCM as well as IBS-SSS score in the herbal-moxa plaster group were lower than those in the moxa-box moxibustion group (P<0.05). Compared with those before treatment, the IBS-QOL scores in the two groups were increased after treatment (P<0.05), and the IBS-QOL score in the herbal-moxa plaster group was higher than that in the moxa-box moxibustion group (P<0.05). The total effective rate was 92.5% (37/40) in the herbal-moxa plaster group, which was higher than 85.0% (34/40) in the moxa-box moxibustion group (P<0.05). CONCLUSION: On the basis of conventional acupuncture treatment, herbal-moxa plaster could effectively improve the clinical symptoms and quality of life in IBS-D patients of spleen and kidney yang deficiency, and its efficacy is superior to that of moxa-box moxibustion.

The Paeonia qiui R2R3-MYB Transcription Factor PqMYBF1 Positively Regulates Flavonol Accumulation.

Tree peony is a "spring colored-leaf" plant which has red leaves in early spring, and the red color of the leaves usually fades in late spring. Flavonols are one subgroup of flavonoids, and they affect the plant organs' color as co-pigments of anthocyanins. To investigate the color variation mechanism of leaves in tree peony, PqMYBF1, one flavonol biosynthesis-related MYB gene was isolated from Paeonia qiui and characterized. PqMYBF1 contained the SG7 and SG7-2 motifs which are unique in flavonol-specific MYB regulators. Subcellular localization and transactivation assay showed that PqMYBF1 localized to the nucleus and acted as a transcriptional activator. The ectopic expression of PqMYBF1 in transgenic tobacco caused an observable increase in flavonol level and the anthocyanin accumulation was decreased significantly, resulting in pale pink flowers. Dual-luciferase reporter assays showed that PqMYBF1 could activate the promoters of PqCHS, PqF3H, and PqFLS. These results suggested that PqMYBF1 could promote flavonol biosynthesis by activating PqCHS, PqF3H, and PqFLS expression, which leads metabolic flux from anthocyanin to flavonol pathway, resulting in more flavonol accumulation. These findings provide a new train of thought for the molecular mechanism of leaf color variation in tree peony in spring, which will be helpful for the molecular breeding of tree peony with colored foliage.