Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.

Influence of Reactive Volatile Organic Compounds on Ozone Production in Houston-Galveston-Brazoria Area

Secondary pollutant ozone (O3) formation in a particular area is often influenced by various factors. Source of emissions is one of the factors. In south east Texas, Houston-Galveston-Brazoria (HGB) is a marginal non-attainment area for ozone (O3). A summer episode of May 28 to July 2, 2006 is simulated using Comprehensive Air Quality Model with extensions (CAMx). During this period O3 concentration in HGB often exceeds the National Ambient Air Quality Standards (NAAQS) 0.075 ppm of average 8 hour O3 concentration. HGB area has numerous point sources. Various studies found that some specific volatile organic compounds are very reactive in atmosphere. The objective of this study is to analyze the influence of volatile organic compounds present in point source emissions on the air quality of HGB area. For this purpose ozone sensitivity for HGB area is analyzed by the ratio of hydrogen peroxides (H2O2) to nitric acid (HNO3). HGB area is found NOx limited but reactive VOCs are found to be influential too. From (1-4 June, 2006) maximum O3 concentration was found on weekend, June 3. VOCs such as Acetaldehyde (ALD2), Formaldehyde (FORM) and Alkane (ETHA) showed good correlation with O3 concentrations on that day. In addition, Peroxyacetyl nitrate (PAN) formation was found correlated to higher ozone production. Criteria pollutant Sulfur dioxide (SO2) was found to influence the ALD2 and ETHA concentrations, and thus indirectly influenced O3 production.

Estimating the Yield Loss of Winter Wheat from Drought in the United States Southern Plains Region as Influenced by El Niño-Southern Oscillation (ENSO)

Wheat (Triticum aestivum L.) production is a major economic activity in most regional and rural areas in the Southern Plains, a semi-arid region of the United States. This region is vulnerable to drought and is projected to experience a drier climate in the future. Since the interannual variability in climate in this region is linked to an ocean-atmospheric phenomenon, called El Niño-Southern Oscillation (ENSO), droughts in this region may be associated with ENSO. Droughts that occur during the critical growth phases of wheat can be extremely costly. However, the losses due to an impending drought can be minimized through mitigation measures if it is predicted in advance. Predicting the yield loss from an imminent drought is crucial for stakeholders. One of the reliable ways for such prediction is using a plant physiology-based agricultural drought index, such as Agricultural Reference Index for Drought (ARID). This study developed ENSO phase-specific, ARID-based models for predicting the drought-induced yield loss for winter wheat in this region by accounting for its phenological phase-specific sensitivity to drought. The reasonable values of the drought sensitivity coefficients of the yield model for each ENSO phase (El Niño, La Niña, or Neutral) indicated that the yield models reflected reasonably well the phenomena of water stress decreasing the winter wheat yields in this region during different ENSO phases. The values of various goodness-of-fit measures used, including the Nash-Sutcliffe Index (0.54 to 0.67), the Willmott Index (0.82 to 0.89), and the percentage error (20 to 26), indicated that the yield models performed fairly well at predicting the ENSO phase-specific loss of wheat yields from drought. This yield model may be useful for predicting yield loss from drought and scheduling irrigation allocation based on the phenological phase-specific sensitivity to drought as impacted by ENSO.

Discarded Carbon-Zinc Batteries as Source of an Efficient Heterogeneous Fenton-Like Catalyst Employed to Degrade Organic Molecules in an Aqueous Medium

The present work evaluates the feasibility of using the raw material collected from discarded zinc-carbon batteries as heterogeneous catalyst to degrade the dye Indigo Carmine in an aqueous solution. Besides the evident environmental application, this work also presents an economic alternative for the production of new catalysts used to remediate polluted waters. For this, discarded carbon-zinc batteries were gathered, disassembled and their anodic paste collected. After acidic treatment and calcination at 500°C, characterization measurements, i.e. flame atomic absorption spectroscopy (FAAS), nitrogen sorption, X-ray diffraction (XRD) and scanning electron microscopy (SEM), revealed that the so-obtained material consisted mainly of ZnMn2O4. This material acts as a heterogeneous catalyst in a Fenton-like process that degrades the dye Indigo Carmine in water. That is probably due to the presence of Mn(III) (manganese in the +3 oxidation state) in this material that triggers the decomposition of hydrogen peroxide (H2O2) to yield hydroxyl radicals (HO·). Moreover, direct infusion electrospray ionization coupled to high resolution mass spectrometry (ESI-HRMS) was employed to characterize the main by-products resulting from such degradation process. These initial results thus indicate that raw materials from waste batteries can therefore be potentially employed as efficient Fenton-like catalysts to degrade organic pollutants in an aqueous solution.

SIRT1 and stem cells: In the forefront with cardiovascular disease, neurodegeneration and cancer

Cardiovascular disease, nervous system disorders, and cancer in association with other diseases such as diabetes mellitus result in greater than sixty percent of the global annual deaths. These noncommunicable diseases also affect at least one-third of the population in low and middle-income countries and lead to hypertension, elevated cholesterol, malignancy, and neurodegenerative disorders such as Alzheimer's disease and stroke. With the climbing lifespan of the world's population, increased prevalence of these disorders is expected requiring the development of new therapeutic strategies against these disabling disease entities. Targeting stem cellproliferation for cardiac disease, vascular disorders, cancer, and neurodegenerative disorders is receiving great enthusiasm, especially those that focus upon SIRT1, a mammalian homologue of the yeast silent information regulator-2. Modulation of the cellular activity of SIRT1 can involve oversight by nicotinamide/nicotinic acid mononucleotide adenylyltransferase, mammalian forkhead transcription factors, mechanistic of rapamycin pathways, and cysteine-rich protein 61, connective tissue growth factor, and nephroblastoma over-expressed gene family members that can impact cytoprotective outcomes. Ultimately, the ability of SIRT1 to control the programmed cell death pathways of apoptosis and autophagy can determine not only cardiac, vascular, and neuronal stem cell development and longevity, but also the onset of tumorigenesis and the resistance against chemotherapy. SIRT1 therefore has a critical role and holds exciting prospects for new therapeutic strategies that can offer reparative processes for cardiac, vascular, and nervous system degenerative disorders as well as targeted control of aberrant cell growth during cancer.

Disposal and Treatment Methods for Pesticide Containing Wastewaters: Critical Review and Comparative Analysis

Pesticides provide the primary means for controlling organisms that compete with man for food and fibre or cause injury to man, livestock and crops. They played a vital role in the economic production of wide ranges of vegetable, fruit, cereal, forage, fibre and oil crops which now constitute a large part of successful agricultural industry in many countries. After application to the target areas, pesticide residues are removed from applicators by rinsing with water which results in the formation of a toxic wastewater that represents a disposal problem for many farmers. Pesticides can adversely affect people, pets, livestock and wildlife in addition to the pests they are intended to destroy. The phenomenon of biomagnification of some pesticides has resulted in reproductive failure of some fish species and egg shell thinning of birds such as peregrine falcons, sparrow hawk and eagle owls. Pesticide toxicity to humans include skin and eye irritation and skin cancer. Therefore, care must be exercised in the application, disposal and treatment of pesticides. Currently, disposal of pesticide wastewater is carried out by: 1) land cultivation, 2) dumping in soil pits, plastic pits and concrete pits or on land and in extreme cases in streams near the rinsing operation, 3) use of evaporation beds and 4) land filling. These methods of disposal are unsafe as the surface run off will reach streams, rivers and lakes and the infiltration of the wastewater into the local soil will eventually reach ground water. The treatment methods currently used for pesticide wastewater include: 1) incineration (incinerators and open burning), 2) chemical treatments (O3/UV, hydrolysis, Fenton oxidation and KPEG), 3) physical treatments (inorganic, organic absorbents and activated carbon) and 4) biological treatments (composting, bioaugmentation and phytoremediation). Therefore, the choice of safe, on farm disposal techniques for agricultural pesticides is very important. A comparative analysis was performed on 18 methods of pesticide disposal/treatment using six criteria: containment, detoxification ability, cost, time, suitability for on farm use, size and evaporation efficiency. The results indicated that of the 18 methods evaluated, 9 scored above 80/100 and can be used on farm. They were organic absorbents (97), composting (94), bioaugmentation (92), inorganic absorbents (90), Fenton oxidation (86), O3/UV (83), activated carbon (82), hydrolysis (82), and land cultivation (80). The other methods are not suitable for on farm use as they suffered from containment problems, high cost and variability of effectiveness.

LiCoO_2梯度包覆LiNi_(0.96)Co_(0.04)O_2电极材料的电化学性能

LiCoO2 gradient coated LiNi0.96Co0.04O2 material and iso-structure LiNi0.8Co0.2O2 material (the same molar ratio 8/2 of Ni/Co in the two materials) as cathode for lithium-ion batteries were synthesized with a co-precipitation method. Microstructure of iso-structure LiNi0.8Co0.2O2 were about the same as that of LiNiO2, and the structure of the coated material was much more similar to that of LiCoO2 based on the X-ray diffraction patterns. The cycling voltammetry and galvanostatic cycle tests show that the properties of the coated material were improved significantly. The first specific charge and discharge capacity for the coated material was 249.20 mAh·g-1 and 207.90 mAh·g-1 respectively, and the specific discharge capacity for the 100th cycle was still 186.02 mAh·g-1 with an irreversible loss of only 21.1 mAh·g-1. This showed that the new material had a good lithium intercalation-deintrercalation performance. Meanwhile, the mechanism of the sintering reaction was proposed. During the sintering reaction of the precursor with LiOH, the Li+-ion permeated into the body of precursors because the shape of the precursor particles was not changed basically based on scanning electronic microscopy. So, the layer microstructure of the precursor is important for the layer microstructure of lithium nickel cobalt oxides electrode material.

Astragaloside Ⅳ protects RGC-5 cells against oxidative stress

Astragaloside Ⅳ is the main active compound of Astragalus membranaceus. Astragaloside Ⅳ has strong anti-oxidative activities and protective effects against progression of peripheral neuropathy. In this study, we determined whether astragaloside Ⅳ protects retinal ganglion cells（RGC） from oxidative stress injury using the rat RGC-5 cell line. Hydrogen peroxide（H_2O_2） was used to induce oxidative stress injury, with the protective effect of astragaloside Ⅳ examined. Cell Counting Kit-8 and 4′,6-diamidino-2-phenylindole staining showed that astragaloside Ⅳ increased cell survival rate and decreased apoptotic cell number. Flow cytometry showed that astragaloside Ⅳ decreased H_2O_2-induced reactive oxygen species levels. While laser confocal microscopy showed that astragaloside Ⅳ inhibited the H_2O_2-induced decrease of mitochondrial membrane potential. Western blot assay showed that astragaloside Ⅳ reduced cytochrome c release induced by H_2O_2, inhibited Bax and caspase-3 expression, and increased Bcl-2 expression. Altogether, these results indicate that astragaloside Ⅳ has potential protective effects against H_2O_2-induced oxidative stress in retinal ganglion cells.

溶胶-凝胶新方法合成介孔铁酸铜纳米粉体催化剂上CO低温氧化(英文)

Mesoporous CuFe2O4 solid solution nanopowders with high specific surface areas were synthesized by a novel, very simple and inexpensive sol-gel route using propylene oxide as gelation agent, and used as the catalyst in low temperature CO oxidation. The samples were characterized by X-ray diffraction, N2 adsorption-desorption, thermogravimetric/differential thermal analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and temperature-programmed reduction. The results revealed that the samples have a nanocrystalline structure with crystals in the range of 10 to 25 nm, and that all the catalysts have mesoporous pores. The addition of Cu into iron oxide affected its structural and catalytic properties. The sample containing 15 mol% Cu showed the highest specific surface area and catalytic activity, and showed high catalytic stability in low temperature CO oxidation.

Advanced glycation end products induce neural tube defects through elevating oxidative stress in mice

Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube development, C57BL/6 female mice were fed for 4 weeks with com- mercial food containing 3% advanced glycation end product bovine serum albumin （AGE-BSA） or 3% bovine serum albumin （BSA） as a control. After mating mice, oxidative stress markers including malondialdehyde and H202 were measured at embryonic day 7.5 （E7.5） of ges- tation, and the level of intracellular reactive oxygen species （ROS） in embryonic cells was determined at E8.5. In addition to evaluating NTDs, an enzyme-linked immunosorbent assay was used to determine the effect of embryonic protein administration on the N-（carboxymethyl） lysine reactivity of acid and carboxyethyl lysine antibodies at E10.5. The results showed a remarkable increase in the incidence of NTDs at El0.5 in embryos of mice fed with AGE-BSA （no hyperglycemia） compared with control mice. Moreover, embryonic protein administration resulted in a noticeable increase in the reactivity of N-（carboxymethyl） lysine and N（ε）-（carboxyethyl） lysine antibodies. Malondialdehyde and H2O2 levels in embryonic cells were increased at E7.5, followed by increased intracellular ROS levels at E8.5. Vitamin E supplementation could partially recover these phenomena. Collectively, these results suggest that AGE-BSA could induce NTDs in the absence of hyperglycemia by an underlying mechanism that is at least partially associated with its capacity to increase embryonic oxidative stress levels.

Distribution of Ag(I), Li(I)-Cs(I) Picrates, and Na(I) Tetraphenylborate with Differences in Phase Volume between Water and Diluents

Ionic strength conditions in distribution experiments with single ions are very important for evaluating their distribution properties. Distribution experiments of picrates (MPic) with M = Ag(I) and Li(I)-Cs(I) into o-dichlorobenzene (oDCBz) were performed at 298 K by changing volume ratios (Vorg/V) between water and oDCBz phases, where “org” shows an organic phase. Simultaneously, an analytic equation with the Vorg/V variation was derived in order to analyze such distribution systems. Additionally, the AgPic distribution into nitrobenzene (NB), dichloromethane, and 1,2-dichloroethene (DCE) and the NaB(C6H5) 4 (=NaBPh4) one into NB and DCE were studied at 298 K under the conditions of various Vorg/V values. So, extraction constants (Kex) for MPic into the org phases, their ion-pair formation constants (KMA,org) for MA = MPic in the org ones, and standard distribution constants () for the M(I) transfers between the water and org bulk phases with M = Ag and Li-Cs were determined at the distribution equilibrium potential (dep) of zero V between the bulk phases and also the Kex (NaA), KNaA,org, and values were done at A-=BPh-4. Here, the symbols Kex, KMA,org, and or were defined as [MA] org/[M+][A-], [MA] org/[M+]org [A-]org, and [M+]org/[M+] or [A-]org/[A-] at dep = 0, respectively. Especially, the ionic strength dependences of Kex and KMPic,org were examined at M = Li(I)-K(I) and org = oDCBz. From above, the conditional distribution constants, KD,BPh4 and KD,Cs, were classified by checking the experimental conditions of the I, Iorg, and dep values.

Electrokinetic-mechanism of water and furfural oxidation on pulsed laser-interlaced Cu_(2)O and CoO on nickel foam

The electrocatalytic oxidation of biomass-derived furfural(FF)feedstocks into 2-furoic acid(FA)holds immense industrial potential in optics,cosmetics,polymers,and food.Herein,we fabricated Co O/Ni O/nickel foam(NF)and Cu_(2)O/Ni O/NF electrodes via in situ pulsed laser irradiation in liquids(PLIL)for the bifunctional electrocatalysis of oxygen evolution reaction(OER)and furfural oxidation reaction(FOR),respectively.Simultaneous oxidation of NF surface to NiO and deposition of CoO and/or Cu_(2)O on NF during PLIL offer distinct advantages for enhancing both the OER and FOR.CoO/NiO/NF electrocatalyst provides a consistently low overpotential of~359 m V(OER)at 10 m A/cm^(2),achieving the maximum FA yield(~16.37 m M)with 61.5%selectivity,79.5%carbon balance,and a remarkable Faradaic efficiency of~90.1%during 2 h of FOR at 1.43 V(vs.reversible hydrogen electrode).Mechanistic pathway via in situ electrochemical-Raman spectroscopy on CoO/NiO/NF reveals the involvement of phase transition intermediates(NiOOH and CoOOH)as surface-active centers during electrochemical oxidation.The carbonyl carbon in FF is attacked by hydroxyl groups to form unstable hydrates that subsequently undergo further oxidation to yield FA products.This method holds promise for large-scale applications,enabling simultaneous production of renewable building materials and fuel.

Facile preparation of N-doped corncob-derived carbon nanofiber efficiently encapsulating Fe2O3 nanocrystals towards high ORR electrocatalytic activity

Facile preparation of cost-effective and durable porous carbon-supported non-precious-metal/nitrogen electrocatalysts for oxygen reduction reaction(ORR)is extremely important for promoting the commercialized applications of such catalysts.In this work,the FeCl3-containing porphyrinato iron-based covalent porous polymer(FeCl3·FeP or-CPP)was fabricated in-situ onto porous corncob biomass supports via a simple one-pot method.Subsequent thermal-reduction pyrolysis at 700℃-900℃with CO2 gas as an activating agent resulted in Fe2O3-decorated and N-doped graphitic carbon composite Fe2O3@NC&bio-C with a high degree of graphitization of Fe-involved promotion during pyrolysis(Fe2O3=FeCl3·FePor-CPP derived Fe2O3;NC=N-doped graphene analog;bio-C=the corncob-derived hierarchically porous graphitic biomass carbon framework).The derivedα-Fe2O3 andγ-Fe2O3 nanocrystals(5-10 nm particle diameter)were all immobilized on the N-doped bio-C micro/nanofibers.Notably,the Fe2O3@NC&bio-C obtained at the pyrolysis temperature of 800℃(Fe2O3@NC&bio-C-800),exhibited unusual ORR catalytic efficiency via a 4-electron pathway with the onset and half-wave potentials of 0.96 V and 0.85 V vs.RHE,respectively.In addition,Fe2O3@NC&bio-C-800 also exhibited a high and stable limiting current density of-6.0 mA cm-2,remarkably stability(larger than 91%retention after 10000 s),and good methanol tolerance.The present work represents one of the best results for iron-based biomass material ORR catalysts reported to date.The high ORR activity is attributed to the uniformly distributedα-Fe2O3 andγ-Fe2O3 nanoparticles on the N-enriched carbon matrix with a large specific surface area of 772.6 m^2 g^-1.This facilitates favor faster electron movement and better adsorption of oxygen molecules on the surface of the catalyst.Nevertheless,comparative studies on the structure and ORR catalytic activity of Fe2O3@NC&bioC-800 with Fe2O3@bio-C-800 and NC&bio-C-800 clearly highlight the synergistic effect of the coexisting Fe2O3 nanocrystals,NC,and bio-C on the ORR performance.

Lessons from Vibrio Pathogen and the Comparative Study of Vaccines Developed

Cholera continues to be one of the most common causes of morbidity and mortality among children and adults in developing countries. Vaccine against cholera is an approach in the control of this epidemic and pandemic disease. From the development of very early oral cholera vaccine, advances in vaccine development documented due to a good illustration of the epidemiology, outbreak strategy, and pathophysiology of the disease causing pathogen. The newer-generation oral cholera vaccines are safe and guarantee a high level of protection during outbreak settings for several years. Yet infants and young children in developing countries are hyporesponsive to vaccines and show poor protection against cholera. In this review, we survey and analyse our current knowledge on the etiology of cholera, its clinical manifestation, global epidemiology and elaborate the vaccine candidates, which are effective against the pathogen and the corresponding immune responses to the available vaccines. These reviews comprehensively cover the salient features of recent discoveries related to Vibrio cholerae virulence, past and present vaccine candidates and their advantages and disadvantages with their development strategies. We believe that the advances that have been included in this review will give a comprehensive insight to the prevention and control of cholera outbreaks and development of effective cholera vaccines.

化学处理对托鲁巴姆(Solanum Torvum)种子发芽的影响

论文通过15种化学试剂处理托鲁巴姆种子发现,CaCl2、H2O2和H3BO3不能促进托鲁巴姆种子萌发,发芽率低于对照清水处理;Ca(NO3)2和NaNO3处理虽然对萌发有促进作用,但种子发芽延缓,发芽率不高;KH2PO、K2HPO4、NH4NO3、CaCO3、MnCl2、KCl和NaCl处理对发芽也有促进作用,但发芽效果不明显;KNO3、NaNO2和K3PO4处理发芽率和发芽势都较高,是试剂中较好的类型。采用0.3%～2.0%K3PO4浸种36～48h、0.5%～1.0%KNO3浸种36～48h、0.1%～0.5%NaNO3浸种48h都可使种子发芽率达85%以上,基本达到生产要求,可以作为种子处理的方法。其中K3PO4处理效果最好,NaNO3较好,KNO3对处理浓度和浸种时间要求较严格。

Vertical profile of aerosol extinction based on the measurement of O4 of multi-elevation angles with MAX-DOAS

A method for aerosol extinction profile retrieval using ground-based multi-axis differential optical absorption spectroscopy(MAX-DOAS)is studied,which is based on a look-up table algorithm.The algorithm uses parametric method to represent aerosol extinction profiles and simulate different atmospheric aerosol states through atmospheric radiation transfer model.Based on the method,aerosol extinction profile was obtained during six cloud-free days.The O4 differential air mass factor(dAMF)measured by MAX-DOAS is compared with the corresponding model results under different atmospheric conditions(R^2=0.78).The aerosol optical thickness,aerosol weight factor in boundary layer,and the height of the boundary layer are obtained after the process of minimization and look-up table method.The retrieved aerosol extinction in boundary layer is compared with PM2.5 data measured by ground point instrument.The diurnal variation trends of the two methods are in good agreement.The correlation coefficients of the two methods are 0.71 when the aerosol optical thickness is smaller than 0.5.The results show that the look-up table method can obtain the aerosol state of the troposphere and provide validation for other instrument data.

Interhemispheric and longitudinal differences in the ionosphere-thermosphere coupling process during the May 2024 superstorm

Geomagnetic storm events have a strong influence on the ionosphere–thermosphere(I-T)coupling system.Analyzing the regional response process of the I-T system and its differences across the northern and southern hemispheres is an important but challenging task.In this study,we used a combination of multiple observations and a model simulation to examine the north–south hemispheric difference in the I-T coupling system in the American and Asian sectors during the geomagnetic superstorm that occurred in May 2024.Observations of the total electron content(TEC)showed that the Asian sector had negative storms in the northern hemisphere and positive storms in the southern hemisphere,a process that exacerbated the hemispheric differences in the TEC.However,both hemispheres of the American sector showed negative storms.The thermospheric composition changes also differed between the two sectors,and their variation could partially explain the hemispheric differences caused by positive and negative storms.Moreover,the influence of the thermospheric density change was less than that of the thermospheric composition.Finally,the dynamic effect of the thermospheric wind and the plasma transport processes strongly modulated the north–south differences in the TEC at nighttime in the American and Asian sectors,respectively,during this superstorm.

Circulation Pattern Controls of Summer Temperature Anomalies in Southern Africa

This study investigates the relationship between circulation patterns and austral summer temperature anomalies in southern Africa. The results show that the formation of continental lows tends to increase the thickness of the lower atmosphere. Further, the distinct variabilities of high and low pressure under the circulation types, influence air mass advection from the adjacent oceans, as well as atmospheric stability over land. Stronger anticyclonic circulation at the western branch of the Mascarene high-pressure system enhances the low-level cold air advection by southeast winds,decreases the thickness, and lowers the temperature over a majority of the land in southern Africa. Conversely, a weaker Mascarene High, coupled with enhanced cyclonic activity in the southwest Indian Ocean increases low-level warm air advection and increases temperature anomalies over vast regions in southern Africa. The ridging of a closed South Atlantic anticyclone at the southern coast of southern Africa results in colder temperatures near the tip of southern Africa due to enhanced low-level cold air advection by southeast winds. However, when the ridge is weak and westerly winds dominate the southern coast of southern Africa, these areas experience temperature increases. The northward track of the Southern Hemisphere mid-latitude cyclone, which can be linked to the negative Southern Annular Mode, reduces the temperature in the southwestern part of southern Africa. Also, during the analysis period, El Ni?o was associated with temperature increases over the central parts of southern Africa;while the positive Indian Ocean dipole was linked to a temperature increase over the northeastern, northwestern, and southwestern parts of southern Africa.

Autocrine IL-8 Contributes to Propionibacterium Acnes-induced Proliferation and Differentiation of HaCaT Cells via AKT/FOXO1/Autophagy

Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the production of interleukin-8(IL-8)by keratinocytes.This study aimed to investigate the role of IL-8 in P.acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism.Methods The P.acnes-stimulated HaCaT cell(a human keratinocyte cell line)model was established.Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1(CXCR1)and C-X-C motif chemokine receptor 2(CXCR2)on HaCaT cells.Cell counting kit-8(CCK-8)assay,5-ethynyl-20-deoxyuridine(EdU)assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P.acnes,the IL-8 neutralizing antibody,the CXCR2 antagonist(SB225002),or the CXCR1/CXCR2 antagonist(G31P).Western blotting,nuclear and cytoplasmic separation,CCK-8 assay,and EdU assay were employed to determine the downstream pathway of CXCR2 after P.acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist,the protein kinase B(AKT)antagonist(AZD5363),or the constitutively active forkhead box O1(FOXO1)mutant.Finally,autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine(3-MA).Results The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P.acnes stimulation.The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P.acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling.In brief,IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis.Subsequently,phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P.acnes-induced keratinocytes.Conclusion This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P.acnes-induced keratinocytes,suggesting a potential therapeutic target for AV.

The ROCK pathway inhibitor Y-27632 mitigates hypoxia and oxidative stress-induced injury to retinal Müller cells

Rho kinase （ROCK） was the first downstream Rho effector found to mediate RhoA-induced actin cytoskeletal changes through effects on myosin light chain phosphorylation. There is abundant evidence that the ROCK pathway participates in the pathogenesis of retinal endothelial injury and proliferative epiretinal membrane traction. In this study, we investigated the effect of the ROCK pathway inhibitor Y-27632 on retinal Müller cells subjected to hypoxia or oxidative stress. Müller cells were subjected to hypoxia or oxidative stress by exposure to CoCl2 or H2O2. After a 24-hour treatment with Y-27632, the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide assay was used to assess the survival of Müller cells. Hoechst 33258 was used to detect apoptosis, while 2′,7′-dichlorodihydrofluorescein diacetate was used to measure reactive oxygen species generation. A transwell chamber system was used to examine the migration ability of Müller cells. Western blot assay was used to detect the expression levels of α-smooth muscle actin, glutamine synthetase and vimentin. After treatment with Y-27632, Müller cells subjected to hypoxia or oxidative stress exhibited a morphology similar to control cells. Y-27632 reduced apoptosis, α-smooth muscle actin expression and reactive oxygen species generation under oxidative stress, and it reduced cell migration under hypoxia. Y-27632 also upregulated glutamine synthetase expression under hypoxia but did not impact vimentin expression. These findings suggest that Y-27632 protects Müller cells against cellular injury caused by oxidative stress and hypoxia by inhibiting the ROCK pathway.