Skin Formation Research Articles

Functional analysis of vitamin D receptor (VDR) using adenovirus vector

Recently, we generated type II rickets model rats, including Vdr(R270L), Vdr(H301Q), Vdr(R270L/H301Q), and Vdr-knockout (KO), by genome editing. All generated animals showed symptoms of rickets, including growth retardation and abnormal bone formation. Among these, only Vdr-KO rats exhibited abnormal skin formation and alopecia. To elucidate the relationship between VDR function and rickets symptoms, each VDR was expressed in human HaCaT-VDR-KO cells using an adenovirus vector. We also constructed an adenovirus vector expressing VDR(V342M) corresponding to human VDR(V346M) which causes alopecia. We compared the nuclear translocation of VDRs after adding 1α,25-dihydroxyvitamin D3 (1,25D3) or 25-hydroxyvitamin D3 (25D3) at final concentrations of 10 and 100 nM, respectively. Both 25D3 and 1,25D3 induced the nuclear translocation of wild type VDR and VDR(V342M). Conversely, VDR(R270L) translocation was observed in the presence of 100 nM 25D3, with almost no translocation following treatment with 10 nM 1,25D3. VDR(R270L/H301Q) failed to undergo nuclear translocation. These results were consistent with their affinity for each ligand. Notably, VDR(R270L/H301Q) may exist in an unliganded form under physiological conditions, and factors interacting with VDR(R270L/H301Q) may be involved in the hair growth cycle. Thus, this novel system using an adenovirus vector could be valuable in elucidating vitamin D receptor functions.

Verrucous epidermal nevi: some aspects of pathogenesis and clinical cases

Verrucous epidermal nevi ― hamartomas of keratinocyte or epidermal appendages, located on the skin or mucous membranes in the form of isolated birthmarks, less often have a linear localization. The pathogenesis of verrucous epidermal nevi has not been fully defined, probably the development of the disease is associated with genetic mutations during embryogenesis and represent a special form of skin mosaicism. Verrucous epidermal nevi are skin pathologies that require attention as potentially dangerous in terms of the development of malignant neoplasms of the skin and due to the possible difficulties in their diagnosis and differential diagnosis.
 Analysis of current data on the pathogenesis and differential diagnosis of various forms of verrucous epidermal nevi, presentation of clinical cases of verrucous epidermal nevi.
 The article considers two clinical cases of linear verrucous epidermal nevus. Studies of the pathogenesis of WEN have shown the presence of changes in expressed proteins by affected skin cells, such as OGN, NT5C3A, ADD1, OLFML1, DHRS1, CALML5, SAMHD1, SFRP2, SPRR1B and SERPINB13. This may indicate the participation in the development of verrucous epidermal nevi of changes in the p53 signaling pathway, the cellular response to a cytokine stimulus, and disturbances in cell adhesion and differentiation of Th1 and Th2 cells. The presented clinical cases describe linear verrucous epidermal nevus in order to study the diagnosis of the disease, based on the clinical picture. The need for differential diagnosis of various forms of verrucous epidermal nevi is due to their clinical and sometimes histological similarity with other skin formations. Immunohistochemical examination, genetic analysis using sequencing of the affected skin exome, and proteomic analysis of proteins expressed by affected skin cells help to carry out differential diagnosis.
 The study of the mechanisms of development of this disease will help not only in differential diagnosis with other skin diseases, but will also allow finding new approaches to its conservative therapy.

Development on potential skin anti-aging agents of Cosmos caudatus Kunth via inhibition of collagenase, MMP-1 and MMP-3 activities

BackgroundSkin aging is associated with degradation of collagen by matrix metalloproteinases (MMPs), which leads to loss of skin elasticity and formation of wrinkles. Cosmos caudatus Kunth (CC) has been traditionally claimed as an anti-aging agent in Malaysia. Despite its well-known antioxidant activity, the anti-aging properties of CC was not validated. PurposeThis study aimed to investigate the anti-aging potential of CC extracts and fractions, particularly their inhibition of collagenase, MMP-1 and MMP-3 activities in human dermal fibroblasts CCD-966SK, followed by isolation, identification and analysis of their bioactive constituents. Study design and methodsDPPH assay was firstly used to evaluate the antioxidant activity throughout the bioactivity-guided fractionation. Cell viability was determined using MTS assay. Collagenase activity was examined, while MMP-1 and MMP-3 expression were measured using qRT-PCR and western blotting. Then, chemical identification of pure compounds isolated from CC fractions was done by using ESIMS, 1H and 13C NMR spectroscopies. HPLC analyses were carried out for bioactive fractions to quantify the major components. ResultsThroughout the antioxidant activity-guided fractionation, fractions CC-E2 and CC-E3 with antioxidant activity and no toxicity towards CCD-966SK cells were obtained from CC 75% ethanol partitioned layer (CC-E). Both fractions inhibited collagenase activity, MMP-1 and MMP-3 mRNA and protein expression, as well as NF-κB activation induced by TNF-α in CCD-966SK cells. 14 compounds, which mainly consists of flavonoids and their glycosides, were isolated. Quercitrin (14.79% w/w) and quercetin (11.20% w/w) were major compounds in CC-E2 and CC-E3, respectively, as quantified by HPLC. Interestingly, both fractions also inhibited the MMP-3 protein expression synergistically, compared with treatment alone. ConclusionThe quantified CC fractions rich in flavonoid glycosides exhibited skin anti-aging effects via the inhibition of collagenase, MMP-1 and MMP-3 activities, probably through NF-κB pathway. This is the first study reported on MMP-1 and MMP-3 inhibitory activity of CC with its chemical profile, which revealed its potential to be developed as anti-aging products in the future.

Кожно-шерстный покров овец при пастбищном и круглогодовом стойловом содержании животных

The positive influence of year-round stabling (in comparison with stabling-pasture) on the formation of skin and wool cover: the total thickness of skin and its separate layers, the density of hair follicles, physical and technical properties and wool shearing has been established in sheep of the Prekos breed. The studied technology in growing of repair young sheep is acceptable in conditions of sheep breeding farms of the Central Black Earth zone.

Enhancement of Wound Healing Efficacy by Chitosan-based Hydrocolloid on Sprague Dawley Rats.

Chitosan-based functional materials have attracted considerable attention worldwide for applications in wound healing, especially in skin wound healing, due to their efficiency in hemostasis, anti-bacterial, and skin regeneration. Various chitosan-based products have been developed for skin wound healing applications, but most of these face limitations in either efficacy or cost-effectiveness. Therefore, there is a need to develop a unique material that can handle all of these concerns and be utilized for acute and chronic wounds. This study investigated mechanisms of new chitosan-based hydrocolloid patches in inflammatory reduction and skin formation by using wound-induced Sprague Dawley Rats. Our study combined a hydrocolloid patch with chitosan to achieve a practical and accessible medical patch that would enhance skin wound healing. Our chitosan-embedded patch has shown a significant influence by preventing wound expansion and inflammation increment on Sprague Dawley rat models. The chitosan patch significantly increased the wound healing rate and accelerated the inflammatory stage by suppressing pro-inflammatory cytokines activity (e.g., TNF-α, IL-6, MCP-1, and IL-1β). Moreover, the product was effective in promoting skin regeneration, demonstrated by the increase in the number of fibroblasts through specific biomarkers (e.g., vimentin, α-SMA, Ki-67, collagen I, and TGF-β1). Our study on the chitosan-based hydrocolloid patches not only elucidated mechanisms of reducing inflammation and enhancing proliferation, but also provided a cost-effective method for skin wound dressing.

A hybrid hydrogel constructed using drug loaded mesoporous silica and multiple response copolymer as an intelligent dressing for wound healing of diabetic foot ulcers.

Traditional wound dressings have poor mechanical properties and a single function, which cannot achieve rapid healing of diabetic wounds in a unique physiological microenvironment. In order to develop multifunctional hydrogel dressings with appropriate biological activity to accelerate wound healing and obtain better clinical therapeutic effects, herein we report a hybrid system based on drug loaded mesoporous silica and injectable polymer hydrogels mixed with hypoglycemic drug metformin (Met) as a dressing for diabetic wounds. Firstly, a copolymer with the phenylboronic acid group in the side group, poly(acrylamide-co-dimethylaminopropylacrylamide-co-methacrylamidophenylboronic acid) (abbreviated as PB), was prepared. PB was mixed with polyvinyl alcohol (PVA) to obtain an injectable hydrogel (named PP) with pH/glucose dual responsiveness, which was formed through the combination of the phenylborate group of PB and o-diol of PVA. In another reaction, polydopamine-modified mesoporous silica nanoparticles (MSN@PDA) were prepared and used to adsorb antibiotic tetracycline hydrochloride (TH) to obtain drug-loaded MSN@PDA-TH nanoparticles. Subsequently, the hybrid hydrogel dressing (abbreviated as PP/MSN@PDA-TH/Met) was obtained by mixing PB, PVA, Met and MSN@PDA-TH. The self-healing, rheological and adhesive properties of the hybrid hydrogel were characterized. The results show that the hydrogel dressing has good physical properties. Met and TH were released in vitro in different pH media and glucose environments. The results show that the hydrogel dressing has dual responsiveness towards pH and glucose, and can continuously release metformin and tetracycline, which is conducive to accelerating wound healing. The antimicrobial activity, ROS clearance ability and biocompatibility of the hydrogel dressing were evaluated. The results indicate that the hydrogel dressing was multifunctional. Finally, a full-thickness wound repair model of diabetic mice induced by streptozotocin (STZ) was established. The hybrid hydrogel dressing was applied to the wound surface of mice. The wound healing testing on diabetic mice confirmed that the wound covered with the hybrid hydrogel dressing was completely healed with the formation of the new skin and hair within 9 days to 12 days. Histological analysis indicates that, compared to the PBS control, the hydrogel dressing did not cause significant inflammation in the wound, and a large number of blood vessels, glands and hair follicles appeared. This study provides a good strategy for multi-drug synergistic treatment of diabetic foot ulcers.

Effectiveness of Post-operative Single-dose Anticoagulant with Compression Therapy in Preventing Deep Vein Thrombosis after Thermal Ablation of Varicose Veins

Abstract Introduction: Deep vein thrombosis (DVT) and pulmonary embolism are relatively common diseases and are amenable to therapy but with a potentially fatal outcome if untreated. It is not clear whether patients undergoing varicose vein surgeries should receive a thromboprophylaxis. Furthermore, there is no consensus amongst surgeons with regard to the prevention of venous thromboembolism in patients undergoing surgical treatment for varicose veins. The objective of our study was to assess the effectiveness of post-operative single-dose anticoagulant with 48 h of compression therapy in preventing DVT after thermal ablation for varicose veins under spinal anaesthesia. Materials and Methods: A prospective observational study was conducted amongst 115 patients undergoing endovenous thermal ablation procedure for varicose veins in the Department of General Surgery, Trivandrum. After obtaining detailed history, all patients were assessed clinically for symptoms and signs of varicose veins and graded according to CEAP grading. The patients underwent pre-operative ultrasound Doppler study as per hospital protocol. Thermal ablation (radiofrequency/laser) was done in all selected patients after getting informed consent. Endovenous thermal ablation of veins was done using radiofrequency probe/laser catheter inserted inside the vein under ultrasound guidance after giving tumescence around the vein with normal saline. Phlebectomy of superficial varicosities was done. After thermal ablation of veins and phlebectomy, compression bandaging was given for the limb and continued for 48 h. Single-dose injection enoxaparin 0.4 ml subcutaneous was given after 8 h of procedure. The patient was encouraged for ambulation after recovery from anaesthesia. The patient was examined for swelling, pain, difference in circumference of limb, haematoma formation and appearance of skin and if indicated Doppler study to detect any presence of DVT at post-operative day (POD) 3, 2nd week and 6th week. Then, the proportion of patients developing DVT was taken as a primary outcome. Results: None of the patients in the study group was detected to have DVT of the lower limb during pre-operative venous Doppler study and none of the patients enrolled showed symptoms or signs of DVT during the clinical assessment at POD 3, 2nd week and 6th week after the procedure and a low incidence of DVT is found after thermal ablation procedures. Conclusion: Our study concludes that the use of post-operative single-dose anticoagulant and 48 h of compression therapy and early ambulation as prophylaxis measures prevents DVT.

Formation of glassy skins in drying polymer solutions: approximate analytical solutions.

We study the formation of a glassy skin at the air interface of drying polymer solutions. We introduce a simple approximation, which is valid for most diffusion problems, and which allows us to derive analytical relationships for the polymer concentration as a function of time. We show that the approximate results differ by less than 15% from those obtained by numerically solving the diffusion equation. We use the approximation to study skin formation in evaporating solutions. We focus on the influence of variations of the mutual diffusion coefficient with concentration, when the latter decreases sharply at high concentrations, as observed in the vicinity of the glass transition. We show that the skin thickness depends very strongly on the exponent characterising the decrease of the diffusion coefficient, in contrast to the polymer volume fraction at the interface, which varies only slightly with the exponent.

Assessment of nutrient intakes of children and adolescents with recessive dystrophic epidermolysis bllosa, severe subtype.

Background and aims: epidermolysis bullosa (EB) is a rare disease presenting with skin fragility and formation of blisters. Constant presence of skin lesions, loss of blood, wastage of heat through the open skin, increased turnover of proteins and infections, result in increased energy, protein, and micronutrient needs. This study investigated the intake adequacy of energy, protein, zinc, iron, and dietary fiber in children with epidermolysis bullosa. Methods: this cross-sectional, analytical study was conducted with children and adolescents of up to 18 years of age with recessive dystrophic EB, severe subtype. Demographic data and clinical manifestations affecting food consumption were collected. Nutritional assessment was performed through anthropometric data. We used a formula to estimate specific energy needs for EB, and ratio of skin lesions was also evaluated to assist in estimating energy needs. A protein adequacy of 115 % to 200 % of the Recommended Dietary Allowance was considered for the adequacy of protein intake. And the Dietary Reference Intake tables according to sex and age were used as a reference for micronutrients. Intake assessment was performed using seven consecutive daily food records. Sip feed consumption was considered for intake assessment. Results: all patients showed undernutrition and presented at least three clinical symptoms that affect food consumption: pseudosyndactyly, microstomy, and blisters in the oral cavity. Sip feed constituted between 20 % and 50 % of the patients' energy intake. Intake of iron and zinc was adequate for most patients (confidence of adequacy ≥ 0.85), while fiber intake was below the reference value. Conclusions: this study underscores the importance of nutritional monitoring for EB patients, which is often interpreted as a skin disease but has enormous nutritional repercussions.

Case of left toe gangrene

Diabetes-Related Complications Affect Many Organ Systems and Are Responsible For The Majority Of Morbidity And Mortality Associated With The Disease. The Vascular Complications of DM Are Subdivided Into Micro Vascular (Retinopathy, Neuropathy, Nephropathy) And Macro Vascular Complications (Coronary Heart Disease [CHD], Peripheral Arterial Disease [PAD], Cerebrovascular Disease). Autonomic Neuropathy Results in Anhidrosis and Altered Superficial Blood Flow in The Foot, Which Promote Drying of The Skin And Fissure Formation. PAD And Poor Wound Healing Impede Resolution of Minor Breaks In The Skin, Allowing Them To Enlarge And To Become Infected. Here In This Case Recurrent Diabetes Non-Healing Ulcer With Other Associated Complaints Witnessed Recovery With Deeper Understanding Of Silica As A Constitutional Remedy.

Clinical, Hematological, and Biochemical Alterations Associated With Early and Late Infection of Lumpy Skin Disease in Cattle in Egypt

This study aimed to investigate clinical, hematological, and biochemical alterations associated with early (during the first week.) and late (after one month) of lumpy skin disease (LSD) infection in cattle infected during an outbreak of LSD in Egypt. Animals which were clinically examined directly after the clinical onset of LSD showed, firm elevated skin nodules that were distributed all over the body, fever (more than 40℃) associated with anorexia, general weakness, reduced milk yield, enlargement of superficial lymph nodes, and edema in the brisket and/or limbs. Examination of the affected animals one month after the disease onset revealed marked weight loss, shrunk of skin nodules and formation of sit fast. There were significant increases in body temperature, pulse and respiratory rate in all animals infected with LSD with significant decrease of ruminal movement compared to control group. DNA extracted from skin samples collected from LSD infected animals showed bands at the expected size (172 base pairs) by partial amplification of viral attachment protein using PCR. Reduced RBCS count, Hb content, HCT, and MCHC values with a significant increase in MCV in all LSD infected cows compared to the control group, while leukogram analysis revealed leucopenia and lymphopenia during the 1st week. Post-infection, however, one month post-infection revealed granulocytic leukocytosis. In addition, all LSD infected cows showed inflammatory thrombocytopenia. Animals during early LSD infection showed significant reduction in total protein, albumin, glucose and TAC and significant increase in ALT, AST, ALP, LDH, CPK, C-troponin-1, total and direct bilirubin, creatinine, K and MDA levels compared to the control group. While animals during late infection showed significant decrease in glucose, ALT, AST, LDH, CPK, C-troponin-1, direct bilirubin, K and MDA levels and significant increase in total protein, albumin and TAC compared to the early infection group. It can be concluded that, LSD infection in cattle revealed critical alterations in some hematological and serum biochemical parameters during both early and late stages of infection with negative impact on different organ functions including skin, muscle, liver, kidney and heart.

A Novel Workflow for Early Time Transient Pressure Data Interpretation in Tight Oil Reservoirs with Physical Constraints

In this work, a novel workflow has been proposed, validated and applied to interpret the early time transient pressure data in tight oil reservoirs with physical constraints. More specifically, the theoretical model was developed to obtain the transient pressure response for a vertical well in tight oil reservoirs with consideration of pseudo threshold pressure gradient (TPG). Then, a physical constraint between the skin factor and formation permeability has been proposed based on the physical meaning of percolation theory. This physical constraint can be applied to determine the lower limit of the skin factor which can reduce the uncertainty during the interpretation process. It is found that the influence range of the skin factor and permeability may partially overlap during the interpretation process without consideration of physical constraints. Additionally, it is found that the equivalent wellbore radius is more reasonable by considering the skin factor constraints. Furthermore, the short-time asymptotic method was applied to separate the small pressure signal at the early time period and a novel type curve was proposed to better analyze the early time pressure response. Subsequently, sensitivity analyses were conducted to investigate the influence of different parameters on the new type curves. It is found that the new type curves are more dispersed and sensitive to the parameters at the early time period which can be beneficial for the early time transient pressure analysis in a tight formation. The proposed method has been validated and then extended to a field application, demonstrating that the transient pressure for a vertical well in a tight formation can be analyzed in a reasonable and accurate manner with only early time transient pressure data.

Piezo‐Augmented and Photocatalytic Nanozyme Integrated Microneedles for Antibacterial and Anti‐Inflammatory Combination Therapy

AbstractWound infection is arguably the most common, and potentially the most devastating, complication of the wound healing process. The ideal treatment strategy has to eliminate bacteria, alleviate inflammation, and promote wound healing and skin formation. Herein, a multifunctional heterostructure is designed consisting of ultrasmall platinum–ruthenium nanoalloys and porous graphitic carbon nitride C3N5 nanosheets (denoted as PtRu/C3N5), which concurrently possesses piezoelectric enhanced oxidase ‐mimic nanozyme activity and photocatalytic hydrogen gas production capacity. Moreover, these hybrid nanotherapeutics are integrated in natural hyaluronic acid microneedles, which exhibit almost 100% broad‐spectrum antibacterial efficacy against multiple bacterial strains in vitro and in vivo within 10 min ultrasound treatment, and effectively inhibit inflammation reactions after 1 h visible light irradiation, promising for accelerating the cutaneous wound healing in the bacterial infected mice. This study highlights a competitive strategy for development of all‐in‐one antibacterial and anti‐inflammatory therapies.

Chemical and Biological Investigations of Allium scorodoprasum L. Flower Extracts.

This study was designed to investigate the impact of different extraction solvent systems on the chemical composition and biological activities of Allium scorodoprasum L. (Amaryllidaceae)-the medicinal plant that was traditionally used as a remedy in the medieval period in the Balkans. Targeted chemical analysis of nine different extracts was performed by UHPLC(-)HESI-QqQ-MS/MS. Antimicrobial and antibiofilm activities of the extracts were investigated on sixteen clinical isolates of bacteria, yeasts and dermatomycetes, all isolated from infected human skin and corneal formations. Cytotoxicity and wound-healing properties were tested on human immortalized keratinocytes (HaCaT cell line). Antioxidant activity was assessed by six different assays, while beneficial potential against certain neurodegenerative diseases and type 2 diabetes was determined in selected enzyme inhibition assays coupled with molecular modeling. The results showed that the obtained extracts were rich in phenolic compounds, especially flavonoid glycosides such as rutin and kaempferol 3-O-glucoside. All of the extracts showed antimicrobial, wound-healing, antioxidant and anti-enzymatic properties. This study is the first of its kind, linking the medieval medicinal use of wild-growing flowers of A. scorodoprasum with contemporary in vitro scientific approaches.

Woodpile structural designs to increase the stiffness of mycelium-bound composites

Mycelium-bound composites are biodegradable, eco-friendly materials grown by fungi onto solid ligno-cellulosic substrates. Mycelium is an interconnected network made of fungal cells that bind the substrates' particulates together. Uncompressed mycelium-bound composites have typically weak mechanical properties, similar to that of expanded polystyrene. In this paper, mycelium is grown onto porous woodpile struts structures to increase the final mechanical properties. The hypothesis is that increase in porosity can increase oxygen diffusion throughout the material and increase the development of dense mycelium network. Mycelium-bound composites grown from P. ostreatus onto bamboo microfibers substrates were studied to test this hypothesis. Constructing porous woodpile structures and monitoring the growth and the mechanical properties under compression, it was found that the porosity obtained through the design was able to increase dense fungal mycelium skin formation. As a result, the stiffness of the porous structures was multiplied by 6 after 28 days of growth. The specific modulus was in turned multiplied by 4 with the addition of 30 % macroscopic porosity. Despite the modest mechanical properties (stiffness about 0.5 MPa), the approach proposed illustrates how appropriate structural design can efficiently increase the properties of grown bio-based materials.

Mpox: What Practicing Gastroenterologists Need to Know

Mpox: What Practicing Gastroenterologists Need to Know

Implications of parity-violating electron scattering experiments on 48Ca (CREX) and 208Pb (PREX-II) for nuclear energy density functionals

Recent precise parity-violating electron scattering experiments on 48Ca (CREX) and 208Pb (PREX-II) provide a new insight on the formation of neutron skin in nuclei. Within the energy density functional (EDF) framework, we investigate the implications of CREX and PREX-II data on nuclear matter symmetry energy and isovector properties of finite nuclei: neutron skin thickness and dipole polarizability. The weak-charge form factors from the CREX and PREX-II experiments are employed directly in constraining the relativistic density-dependent point coupling EDFs. The EDF established with the CREX data acquires considerably smaller values of the symmetry energy parameters, neutron skin thickness and dipole polarizability both for 48Ca and 208Pb, in comparison to the EDF obtained using the PREX-II data, and previously established EDFs. Presented analysis shows that CREX and PREX-II experiments could not provide consistent constraints for the isovector sector of the EDFs, and further theoretical and experimental studies are required.

Recombinant Photolyase-Thymine Alleviated UVB-Induced Photodamage in Mice by Repairing CPD Photoproducts and Ameliorating Oxidative Stress.

Cyclobutane pyrimidine dimers (CPDs) are the main mutagenic DNA photoproducts caused by ultraviolet B (UVB) radiation and represent the major cause of photoaging and skin carcinogenesis. CPD photolyase can efficiently and rapidly repair CPD products. Therefore, they are candidates for the prevention of photodamage. However, these photolyases are not present in placental mammals. In this study, we produced a recombinant photolyase-thymine (rPHO) from Thermus thermophilus (T. thermophilus). The rPHO displayed CPD photorepair activity. It prevented UVB-induced DNA damage by repairing CPD photoproducts to pyrimidine monomers. Furthermore, it inhibited UVB-induced ROS production, lipid peroxidation, inflammatory responses, and apoptosis. UVB-induced wrinkle formation, epidermal hyperplasia, and collagen degradation in mice skin was significantly inhibited when the photolyase was applied topically to the skin. These results demonstrated that rPHO has promising protective effects against UVB-induced photodamage and may contribute to the development of anti-UVB skin photodamage drugs and cosmetic products.

Application and Optimization for Network-Fracture Deep Acidizing Technique of Fractured Carbonate Reservoirs

Abstract The fractured carbonate rock reservoir is widespread in Sichuan Basin, and the characteristics of different areas are different. The development of natural fractures is varying degrees, lost circulations occur frequently, and the formation heterogeneity is strong, which causes the formation not sufficiently stimulated by acidizing. It may affect the effectiveness of reservoir stimulation. To advance the whole stimulation effect of the heterogeneous fractured carbonate reservoir, a new solution for determining the invasion radius during drilling in a fracture network reservoir is presented, which is based on solute transport and convection-diffusion equations. It can predict the invasion radius caused by mud loss and determines the range of mud loss invasion, which clarify the scope and degree of reservoir damage. The formation of skin factors polluted by mud loss was calculated. The experiments verified that the acidizing technology can remove reservoir damage and reduce the polluted formation of skin factors. The opening pressure of the nature fracture closed is calculated which can control the acidizing area. It is confirmed how many fractures in the carbonate reservoir can be opened under the wellhead pressure limit, which meets the construction conditions of acidizing fractured reservoirs. The framework of network-fracture deep acidizing technology was established, which can efficiently break through the detrimental zone caused by lost circulation, break down the natural fracture network, and decrease the formation of the skin. The restart pressure of natural fractures was calculated, and the design parameters such as pump pressure and displacement were optimized to quantify the scope of reservoir stimulation and the scale of acid fluid. The technique of network-fracture deep acidizing was applied for well A, the formation of skin after acidizing can be reduced to -4, and the testing production of well A was 58.87×104 m3/d. The technique of network-fracture deep acidizing can quantify the acid scale and sweep area in acid fracturing design, which develops the fracturing efficiency and improves the fracturing engineering.

Establishment of a method to expose and measure pollution in excised porcine skin with electron paramagnetic resonance spectroscopy

Health problems associated with the amount of air pollutants are increasing worldwide. Pollution damages not only the lungs; it also has an impact on skin health and is co-responsible for the development of skin diseases.Anti-pollution products are on the rise in the cosmetic market but so far, there is no established method to directly assess the impact of pollution on the skin and to test the efficacy of anti-pollution products.To address this problem, two different chambers were developed for the reproducible exposure to realistic air pollutant concentrations. One chamber for the exclusive use of excised skin and hair samples, the second chamber for ex vivo and in vivo measurements. Measurements of nicotine next to the investigated skin area allow conclusions to be drawn on the particle concentration to which the skin is exposed. Electron paramagnetic resonance spectroscopy, which enables the detection of free radicals in different systems, was applied to assess the hazard potential of pollution in the skin. A direct proof of the formation of free radicals in the skin by the model pollutant cigarette smoke could be demonstrated. An additional application of UV irradiation even increased the formation of free radicals in the skin seven-fold (sum parameter). Depending on the question of interest, the use of different spin probes allows various assessments of the radical formation in skin: the amount of radicals but also the antioxidant status of the microenvironment can be estimated.Using two exposure chambers, the direct formation of oxidative stress by cigarette smoke on ex vivo skin, with and without additional UV exposure, could be reproducibly examined. This measurement method is promising for the assessment of anti-pollution products and could allow a direct causal connection between pollutant, effect on the skin and the protective function of skin care products.