The effect of artificial light at night (ALAN) on the characteristics of diapause of Aedes albopictus.

BACKGROUND: Recently, the effect of artificial light at night (ALAN) on the physiology and behavior of insects has gradually attracted the attention of researchers and has become a new research topic. Aedes albopictus is an important vector that poses a great public health risk. Further studies on the diapause of Ae. albopictus can provide a basis for new vector control, and it is also worth exploring whether the effect of ALAN on the diapause of Ae. albopictus will provide a reference for the prevention and control of infectious diseases mediated by Ae. albopictus. METHODS: In this study, we experimentally studied the diapause characteristics of different geographical strains of Ae. albopictus under the interference of ALAN, explored the effect of ALAN on the diapause of Ae. albopictus and explored the molecular mechanism of ALAN on the diapause process through RNA-seq. RESULTS: As seen from the diapause incidence, Ae. albopictus of the same geographic strain showed a lower diapause incidence when exposed to ALAN. The differentially expressed genes (DEGs) were mainly enriched in signaling and metabolism-related pathways in the parental females and diapause eggs of the ALAN group. CONCLUSIONS: ALAN inhibits Ae. albopictus diapause. In the short photoperiod induced diapause of Ae. albopictus in temperate strain Beijing and subtropical strain Guangzhou, the disturbance of ALAN reduced the egg diapause rate and increased the egg hatching rate of Ae. albopictus, and the disturbance of ALAN also shortened the life cycle of Ae. albopictus eggs after hatching.

Possible potential spread of Anopheles stephensi, the Asian malaria vector.

BACKGROUND: Anopheles stephensi is native to Southeast Asia and the Arabian Peninsula and has emerged as an effective and invasive malaria vector. Since invasion was reported in Djibouti in 2012, the global invasion range of An. stephensi has been expanding, and its high adaptability to the environment and the ongoing development of drug resistance have created new challenges for malaria control. Climate change is an important factor affecting the distribution and transfer of species, and understanding the distribution of An. stephensi is an important part of malaria control measures, including vector control. METHODS: In this study, we collected existing distribution data for An. stephensi, and based on the SSP1-2.6 future climate data, we used the Biomod2 package in R Studio through the use of multiple different model methods such as maximum entropy models (MAXENT) and random forest (RF) in this study to map the predicted global An. stephensi climatically suitable areas. RESULTS: According to the predictions of this study, some areas where there are no current records of An. stephensi, showed significant areas of climatically suitable for An. stephensi. In addition, the global climatically suitability areas for An. stephensi are expanding with global climate change, with some areas changing from unsuitable to suitable, suggesting a greater risk of invasion of An. stephensi in these areas, with the attendant possibility of a resurgence of malaria, as has been the case in Djibouti. CONCLUSIONS: This study provides evidence for the possible invasion and expansion of An. stephensi and serves as a reference for the optimization of targeted monitoring and control strategies for this malaria vector in potential invasion risk areas.

Potential Global Distribution of the Invasive Mosquito Aedes koreicus under a Changing Climate.

Invasive alien species are a growing threat to natural systems, the economy, and human health. Active surveillance and responses that readily suppress newly established colonies are effective actions to mitigate the noxious consequences of biological invasions. Aedes (Hulecoeteomyia) koreicus (Edwards), a mosquito species native to East Asia, has spread to parts of Europe and Central Asia since 2008. In the last decade, Ae. koreicus has been shown to be a competent vector for chikungunya virus and Dirofilaria immitis. However, information about the current and potential distribution of Ae. koreicus is limited. Therefore, to understand the changes in their global distribution and to contribute to the monitoring and control of Ae. koreicus, in this study, the MaxEnt model was used to predict and analyze the current suitable distribution area of Ae. koreicus in the world to provide effective information.

The predicted potential distribution of Aedes albopictus in China under the shared socioeconomic pathway (SSP)1-2.6.

Aedes albopictus (Skuse) (Diptera: Culicidae) is one of the 100 most invasive species in the world and represents a significant threat to public health. The distribution of Ae. albopictus has been expanding rapidly due to increased international trade, population movement, global warming and accelerated urbanization. Consequently, it is very important to know the potential distribution area of Ae. albopictus in advance for early warning and control of its spread and invasion. We randomly selected 282 distribution sites from 27 provincial-level administrative regions in China, and used the GARP and MaxEnt models to analyze and predict the current and future distribution areas of Ae. albopictus in China. The results showed that the current range of Ae. albopictus in China covers most provinces such as Yunnan and Guizhou Provinces, and the distribution of Ae. albopictus in border provinces such as Tibet, Gansu and Jilin Provinces tend to expand westwards. In addition, the potential distribution area of Ae. albopictus in China will continue to expand westwards due to future climate change under the SSP126 climate scenario. Furthermore, the results of environmental factor filtering showed that temperature and precipitation had a large effect on the distribution probability of Ae. albopictus.

Photo-Activated Circularly Polarized Luminescence Film Based on Aggregation-Induced Emission Copper(I) Cluster-Assembled Materials.

In this study, a pair of chiral copper(I) cluster-assembled materials (R/S-2) was prepared, exhibiting unique photo-response characteristics with a concentration-wavelength correlation property in DMSO solution. By the combination of R/S-2 with a polymethyl methacrylate (PMMA) matrix, the first photo-activated circularly polarized luminescence (CPL) film was developed, the CPL signal (glum =9×10-3 ) of which could be induced by UV light irradiation. Moreover, the film exhibited a reversible photo-response and extremely good fatigue resistance. Mechanism study revealed that the photo-response properties of the R/S-2 solution and film are attributed to the aggregation-induced emission (AIE) characteristics of R/S-2 and a photo-induced deoxygenation process. This study enriches the types of luminescent cluster-assembled molecules and provides a new strategy for the construction of metal cluster-based stimuli-responsive composite materials.

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

Enhancing the Activity of an Alcohol Dehydrogenase by Using "Aromatic Residue Scanning" at Potential Plasticity Sites.

An alcohol dehydrogenase LkADH was successfully engineered to exhibit improved activity and substrate tolerance for the production of (S)-2-chloro-1-(3,4-difluorophenyl)ethanol, an important precursor of ticagrelor. Five potential hotspots were identified for enzyme mutagenesis by using natural residue abundance as an indicator to evaluate their potential plasticity. A semi-rational strategy named "aromatic residue scanning" was applied to randomly mutate these five sites simultaneously by using tyrosine, tryptophan, and phenylalanine as "exploratory residues" to introduce steric hindrance or potential π-π interactions. The best variant Lk-S96Y/L199W identified with 17.2-fold improvement in catalytic efficiency could completely reduce up to 600 g/L (3.1 M) 2-chloro-1-(3,4-difluorophenyl)ethenone in 12 h with >99.5 % ee, giving the highest space-time yield ever reported. This study, therefore, offers a strategy for mutating alcohol dehydrogenase to reduce aromatic substrates and provides an efficient variant for the efficient synthesis of (S)-2-chloro-1-(3,4-difluorophenyl)ethanol.

Evaluation of product conceptual design based on Pythagorean fuzzy set under big data environment.

The concept design evaluation phase of the new product launch is extremely important. However, current evaluation information relies mainly on the a priori knowledge of decision makers and is subjective and ambiguous. For this reason, a conceptual design solution decision model based on Pythagorean fuzzy sets in a big data environment is proposed. Firstly, we use the ability of big data to mine and analyze information to construct a new standard for product concept design evaluation in the big data environment. Secondly, the Pythagorean fuzzy set (PFS), Analytic Hierarchy Process (AHP), and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) are integrated into a decision model. AHP, extended by the Pythagorean fuzzy set, is used to determine the weights of new conceptual design criteria in a big data environment. The Pythagorean fuzzy TOPSIS is used to prioritize alternative conceptual design solutions. The feasibility of the approach is proven with a practical case, the generalizability of the method is confirmed with two descriptive digital cases, and the reliability, validity, and superiority of the process are demonstrated with sensitivity analysis, comparative analysis, and computational complexity analysis.

Reduction of glyoxalase 1 (GLO1) aggravates cerebrovascular remodeling via promoting the proliferation of basilar smooth muscle cells in hypertension.

Uncontrollable vascular smooth cell proliferation is responsible for vascular remodeling during hypertension development. Glyoxalase 1 (GLO1), the major enzyme detoxifying methylglyoxal, has a critical role in regulating proliferation of several cell types. However, little is known whether GLO1 is involved in cerebrovascular remodeling and basilar smooth muscle cell (BASMC) proliferation during hypertension. Here we explored the role of GLO1 in angiotensin II (Ang II)-induced cerebrovascular remodeling and proliferation of BASMCs and the underlying mechanisms. The protein expression of GLO1 in basilar arteries from hypertensive mice was decreased, and GLO1 expression was negatively correlated with medial cross-sectional area and blood pressure in basilar arteries during hypertension. Knockdown of GLO1 promoted while overexpression of GLO1 prevented Ang II-induced cell proliferation and cell cycle transition in BASMCs. These results were related to the inhibitory effects of GLO1 on PI3K/AKT/CDK2 cascade activation upon Ang II treatment. In addition, in vivo study, GLO1 overexpression with adeno-associated virus harboring GLO1 cDNA improved cerebrovascular remodeling in basilar artery tissue during Ang II-induced hypertension development. These data indicate that GLO1 reduction mediates cerebrovascular modeling via PI3K/AKT/CDK2 cascade-dependent BASMC proliferation. GLO1 acts as a negative regulator of hypertension-induced cerebrovascular remodeling and targeting GLO1 may be a novel therapeutic strategy to prevent hypertension-associated cardiovascular complications such as stroke.

Free fatty acid-induced H2O2 activates TRPM2 to aggravate endothelial insulin resistance via Ca2+-dependent PERK/ATF4/TRB3 cascade in obese mice.

Transient Receptor Potential Melastatin-2 (TRPM2) is a nonselective cation channel mediating Ca2+ influx in response to oxidative stress. Given that insulin resistance-related endothelial dysfunction in obesity attributes to fatty-acid-induced reactive oxygen species (ROS) overproduction, in this study, we addressed the possible role of TRPM2 in obesity-related endothelial insulin resistance and the underlying mechanisms. Whole-cell patch clamp technique, intracellular Ca2+ concentration measurement, western blot, vasorelaxation assay, and high-fat diet (HFD)-induced obese model were employed to assess the relationship between TRPM2 and endothelial insulin response. We found that both the expression and activity of TRPM2 were higher in endothelial cells of obese mice. Palmitate rose a cationic current in endothelial cells which was inhibited or enlarged by TRPM2 knockdown or overexpression. Silencing of TRPM2 remarkably improved insulin-induced endothelial Akt activation, nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production, while TRPM2 overexpression resulted in the opposite effects. Furthermore, TRPM2-mediated Ca2+ entry, CaMKII activation and the following activation of PERK/ATF4/TRB3 cascade were involved in the mechanism of obesity or palmitate-induced endothelial insulin resistance. Notably, in vivo study, knockdown of TRPM2 with adeno-associated virus harboring short-hairpin RNA (shRNA) against TRPM2 alleviated endothelial insulin resistance and ameliorated endothelium-dependent vasodilatation in obese mice. Thus, these results suggest that TRPM2-activated Ca2+ signaling is necessary to induce insulin resistance-related endothelial dysfunction in obesity. Downregulation or pharmacological inhibition of TRPM2 channels may lead to the development of effective drugs for treatment of endothelial dysfunction associated with oxidative stress state.

Redox signal-mediated TRPM2 promotes Ang II-induced adipocyte insulin resistance via Ca2+-dependent CaMKII/JNK cascade.

BACKGROUND AND OBJECTIVE: Redox-sensitive transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable, nonselective cation channel which plays a crucial role in various physiological processes. However, little is known whether TRPM2 is involved in adipocyte dysfunction during hypertension. In the present study, we determined the role of TRPM2 in angiotensin II (Ang II)-induced insulin resistance in adipocytes and the underlying mechanisms. METHODS: Ang II-induced adipocyte insulin resistant model was conducted. Data from Ang II-induced hypertensive mice were used to measure the effects of TRPM2 inhibitor on insulin resistance in vivo. Whole-cell patch clamp technique, intracellular Ca2+ concentration measurement, glucose uptake assay, western blot, cDNA and siRNA transfection were employed to investigate the TRPM2/Ca2+/CaMKII/JNK signaling. RESULTS: Ang II rose a cation current similar to that activated by hydrogen peroxide (H2O2) or ADP-ribose (ADPR), which was blocked by TRPM2 inhibitor or TRPM2 siRNA in adipocytes. Knockdown of TRPM2 significantly improved the lowered insulin sensitivity induced by Ang II, including insulin stimulated glucose uptake, phosphorylation of IRS1 and Akt, interaction between IR and IRS1 and the membrane translocation of GLUT4, whereas overexpression of TRPM2 resulted in the opposite effects. These results were related to the potentiated effects of TRPM2 on Ca2+ influx and CaMKII/JNK cascade activation upon Ang II-induced challenge. Notably, the pharmacological TRPM2 inhibitor, N-(p-amylcinnamoyl)anthranilic acid (ACA), was proved to improve insulin sensitivity in adipose tissue during Ang II-induced hypertension progress. CONCLUSIONS: These data suggested that TRPM2 is a positive regulator of Ang II-induced adipocyte insulin resistance via Ca2+/CaMKII/JNK-dependent signaling pathway. Targeting TRPM2 may be a novel therapeutic strategy to treat hypertension-associated insulin resistance.

[Verification of a sporadic Alzheimer disease model in SORL1 gene knockout mice].

OBJECTIVE: To compare the behavioral and pathological features of SORL1 gene knockout mice with those of normal mice and APP/PSE1 mice to verify the feasibility of using SORL1 knockout mice as a model of sporadic Alzheimer disease. METHODS: SORL1 gene of fertilized mouse eggs were edited using Crispr/Case9 technique. SORL1-/- mice were screened and identified by detecting the DNA sequence, and Western blotting was used to detect the expression of SORL1. SORL1-/- mice, control mice and APP/PSE1 mice all underwent Morris water maze test to assess their learning and memory abilities with positioning navigation and space exploration experiments. The expression of APP and Aß in the brain of the mice was detected using immunohistochemistry and Western blotting, respectively. RESULTS: DNA sequencing showed CAAT deletion in SORL1 gene in two chromosomes of SORL1-/- mice, and the control mice had intact SORL1 gene without the deletion; Western blotting did not detect the expression of the SORL1 in the brain of SORL1-/- mice. Morris water maze test showed that in positioning navigation experiment, the average avoidance latency was similar between SORL1-/- mice and APP/PSE1 mice (P>0.05) but increased significantly in both mice as compared with the control group (P<0.05); similar results were obtained in the space exploration experiment. Immunohistochemistry and Western blotting revealed significantly increased APP and Aß expression in the brain tissue of both SORL1-/- mice and APP/PSE1 mice compared with the control mice without significant differences between the two transgenic mice. CONCLUSION: SORL1-/- mice exhibit similar behavioral and pathological changes with APP/PSE1 mice and can be used as a model of sporadic Alzheimer's disease.

[Protective effect of butylphthalide in a cell model of Alzheimer's disease induced by Aß25-35 in Neuro 2a cells].

OBJECTIVE: To study the protective effect of butylphthalide in a cell model of Alzheimer's disease(AD) induced by Aß25-35 in Neuro 2a (N2a) cells. METHODS: N2a cells were divided into AD group, butylphthalide (NBP) group and control group. AD cell model was established by adding 20 µmol/L Aß25-35 to cultured N2a cells. The cells in NBP group were treated with 0.1, 1, 10, or 100 µmol/L NBP 4 h prior to treatment with 20 µmol/L Aß25-35. The cell viability were determined by MTT assay, the cell apoptotic rate were detected by AnnexinV-FITC flow cytometry, and the cell morphological changes were observed under inverted phase contrast microscope. The expression of TNF-α and IL-1ß mRNA were determined by qRT-PCR. RESULTS: Compared with those in the control group, the number of adherent cells was significantly decreased, neurite structures were reduced, and the cell viability was decreased, while the apoptotic rate and expressions of TNF-α and IL-1ß mRNA were increased in AD group (P<0.05). Compared with that in AD group, the number of adherent cells was increased in NBP group and the cell morphology was similar to the normal control cells. The cell viability of N2a cells was increased in NBP group with decreased apoptotic rate and expression of TNF-αand IL-1ß mRNA (P<0.05). CONCLUSION: Butylphthalide can protect against AD in the cell model induced by Aß25-35 possibly by inhibiting the expression of inflammatory cytokines.

In vivo reversion of an inherited mutation in a Chinese patient with Wiskott-Aldrich syndrome.

A spontaneous reversion that restores Wiskott-Aldrich syndrome protein (WASP) expression was reported recently. However, the genetic mechanism underlying the reversion event was unclear. In the present study, a WAS patient with a nonsense mutation (155 C>T, R41X) was followed during a three-year period. No expression of WASP was detected in peripheral blood mononucleated cells (PBMCs) in 2009 and a small population of intracellular WASP positive lymphocytes was detected during the following three years. The increasing trend of the revertant genotype was significant. WASP-expressing cells were present mainly CD56+ NK cells and CD8+ T cells. Sorted WASP+ cells were analyzed, indicating that the population of CD3+ T cells increased from 36.81% to 99.8%. Although the revertant cells in vivo may have a growth advantage, the patient presented a persistent autoimmune disease, thrombocytopenia, and died from extensive pulmonary fibrosis. The results suggest that the clinical consequences of T-cell mosaicism in WAS remain difficult to predict and is not sufficient to fully normalize immune functions in patients with WAS.

Distribution, clinical features and molecular analysis of primary immunodeficiency diseases in Chinese children: a single-center study from 2005 to 2011.

METHODS: Two hundred three children with genetically proven primary immunodeficiency diseases (PIDs) from 197 unrelated families were enrolled from January 2005 to December 2011. RESULTS: On the basis of criteria developed by the International Union of Immunological Societies, 79 patients were diagnosed as "other well-defined immunodeficiency syndromes" (38.9%), 62 (30.6%) with "predominant antibody deficiencies," 26 (12.8%) with "congenital defects of phagocyte," 25 (12.3%) with "T- and B-cell immunodeficiency" and 11 (5.4%) with "diseases of immune dysregulation." The median time to the diagnosis was 27.9 months and the patients had a wide range of clinical presentations. In addition, a total of 23 pathogenic genes were identified and 213 mutations were detected, including 42 novel mutations. CONCLUSIONS: With the increase in the awareness of PIDs and diagnostic competence, more PID patients will be diagnosed and we will be able to more accurately identify the frequency and the distribution of PIDs in the most populous country in the world.

[Preparation of in situ gel systems for the oral delivery of ibuprofen and its pharmacokinetics study in beagle dogs].

The in situ gel systems can form gel in situ after administration to achieve sustained release, thus provides a promising strategy for drug delivery systems. The aim of this study was to design and prepare in situ gel systems for the oral delivery of ibuprofen (IBU-ISG) and study its pharmacokinetics in Beagle dogs. The characteristics of the basic material of gellan gum (Kelcogel, Kel) and sodium alginate (Manugel, M) were studied through investigating the complex viscosity of the Kel or M solution with or without different concentrations of calcium ion or sodium citrate to ascertain the amount range of the excipients. The measurement of complex viscosity of the solution (0. 5% Kel and 1% M) with different concentrations of sodium citrate and calcium ion was carried out to select the suitable proportion of calcium ion and sodium citrate. The formulation of binary IBU-ISG was optimized by monitoring the complex viscosity before gelling in vitro release property. The optimized formulation contains 1.0% sodium alginate, 0.5% gellan gum, 0. 21% sodium citrate and 0.056% calcium chloride. A single oral dose of IBU-ISG and reference formulation (IBU suspension) were given to each of the 6 healthy Beagle dogs, ibuprofen in plasma at different sampling times was determined by RP-HPLC. The pharmacokinetics parameters in 6 Beagle dogs were calculated. The Tmax of IBU-ISG and reference formulation were (1.8 +/- 0.6) and (0.4 +/- 0. 1) h. The Cmax values were (29.2 +/- 7.6) and (37.8 +/- 2.2) microg x mL(-1). The T(1/2) were (2.3 +/- 0.5) and (2.0 +/- 0.9) h, and the AUC(0-t) were (131.0 +/- 38.6) and (117.3 +/- 23.1) microg x mL(-1) x h, respectively. The binary IBU-ISG was successfully prepared.

Separation of cefoperazone enantiomers using beta-cyclodextrin as chiral additive by capillary zone electrophoresis.

A capillary electrophoresis method was developed to separate the enantiomers of cefoperazone. Different cyclodextrins, including alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), gamma-cyclodextrin (gamma-CD), 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and methyl-beta-cyclodextrin (Me-beta-CD), were tested as chiral additives in the running buffer. The effect of various parameters on enantioseparation such as concentration of NaH(2)PO(4), buffer pH, and CD concentration was also studied. The cefoperazone enantiomers were baseline separated under conditions of 0.04 mmol/L beta-CD, 75 mmol/L NaH(2)PO(4) buffer at pH 4.0. A fused silica capillary (40 cm effective length x 75 microm ID) was used. The applied voltage and capillary temperature were 20 kV and 25 degrees C, respectively. Under these conditions, linear calibration curves were obtained in the 5-500 microg/ml range using UV detection at 280 nm. The limit of detection for both isomers was 0.1 microg/ml. The method was used for the analysis of different pharmaceutical preparations (dose) and biological samples containing cefoperazone.

Restricted-access media high pressure liquid chromatography vs fluorescence polarization immunoassay for analysis of carbamazepine in human plasma.

AIM: To compare restricted-access media high performance liquid chromatographic (RAM-HPLC) method with fluorescence polarization immunoassay (FPIA) for analysis of carbamazepine (CBZ) in human blood. METHODS: An RAM-HPLC method was established for the determination of CBZ in plasma. RESULTS: The two methods do not need sample clean-up prior to analysis and they have almost 100 % recovery and good reproducibility. There is a good correlation between the CBZ concentration in venous plasma samples determined by FPIA and that in both venous and fingertip plasma samples obtained by RAM-HPLC, the correlation coefficients being 0.989 and 0.995, respectively. It is shown by t-test that the data sets of venous and fingertip plasma samples given by RAM-HPLC are consistent with each other but significantly different from the results obtained by FPIA. CONCLUSION: Both direct injection RAM-HPLC and FPIA may be applied in determining CBZ in therapeutic drug monitoring (TDM). FPIA is well-suited to the routine TDM. RAM-HPLC is more useful in TDM related research and especial cases.