A new lymphedema treatment using pyro-drive jet injection.

Lymphedema, resulting from impaired lymphatic drainage, causes inflammation, fibrosis and tissue damage leading to symptoms such as limb swelling and restricted mobility. Despite various treatments under exploration, no standard effective therapy exists. Here a novel technique using the pyro-drive jet injection (PJI) was used to create artificial clefts between collagen fibers, which facilitated the removal of excess interstitial fluid. The PJI was used to deliver a mixture of lactated Ringer's solution and air into the tail of animals with secondary skin edema. Edema levels were assessed using micro-CT scanning. Histopathological changes and neovascularization were evaluated on the injury-induced regenerative tissue. Regarding tissue remodeling, we focused on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF)-C. PJI markedly diminished soft tissue volume in the experimental lymphedema animals compared to the non-injected counterparts. The PJI groups exhibited a significantly reduced proportion of inflammatory granulation tissue and an enhanced density of lymphatic vessels and α-smooth muscle actin (αSMA)-positive small vessels in the fibrous granulation tissue compared to the controls. In addition, PJI curtailed the prevalence of CTGF- and VEGF-C-positive cells in regenerative tissue. In a lymphedema animal model, PJI notably ameliorated interstitial edema, promoted lymphatic vessel growth, and bolstered αSMA-positive capillaries in fibrous granulation tissue. PJI's minimal tissue impact post-lymph node dissection indicates significant potential as an early, standard preventative measure. Easily applied in general clinics without requiring specialized training, it offers a cost-effective and highly versatile solution to the management of lymphedema.

Mining association rules between the granulation feasibility and physicochemical properties of aqueous extracts from Chinese herbal medicine in fluidized bed granulation.

Fluidized bed granulation (FBG) is a widely used granulation technology in the pharmaceutical industry. However, defluidization caused by the formation of large aggregates poses a challenge to FBG, particularly in traditional Chinese medicine (TCM) due to its complex physicochemical properties of aqueous extracts. Therefore, this study aims to identify the complex relationships between physicochemical characteristics and defluidization using data mining methods. Initially, 50 types of TCM were decocted and assessed for their potential influence on defluidization using a set of 11 physical properties and 10 chemical components, utilizing the loss rate as an evaluation index. Subsequently, the random forest (RF) and Apriori algorithms were utilized to uncover intricate association rules among physicochemical characteristics and defluidization. The RF algorithm analysis revealed the top 8 critical factors associated with defluidization. These factors include physical properties like glass transition temperature (Tg) and dynamic surface tension (DST) of DST100ms, DST1000ms, DST10ms and conductivity, in addition to chemical components such as fructose, glucose and protein contents. The results from Apriori algorithm demonstrated that lower Tg and conductivity were associated with an increased risk of defluidization, resulting in a higher loss rate. Moreover, DST100ms, DST1000ms and DST10ms exhibited a contrasting trend in the physical properties Specifically, defluidization probability increases when Tg and conductivity dip below 29.04℃ and 6.21 ms/m respectively, coupled with DST10ms, DST100ms and DST1000ms values exceeding 70.40 mN/m, 66.66 mN/m and 61.58 mN/m, respectively. Moreover, an elevated content of low molecular weight saccharides was associated with a higher occurrence of defluidization, accompanied by an increased loss rate. In contrast, protein content displayed an opposite trend regarding chemical properties. Precisely, the defluidization likelihood amplifies when fructose and glucose contents surpass 20.35 mg/g and 34.05 mg/g respectively, and protein concentration is less than 1.63 mg/g. Finally, evaluation criteria for defluidization were proposed based on these results, which could be used to avoid this situation during the granulation process. This study demonstrated that the RF and Apriori algorithms are effective data mining methods capable of uncovering key factors affecting defluidization.

La-MOFs in situ loaded Al2O3 particles for effective removal of phosphate in water: characterization, application potential analysis, and mechanism.

Excessive phosphorus in water would cause eutrophication and deterioration of the ecological environment. Herein, the La-MOFs/Al2O3 composite was successfully prepared by the in situ hydrothermal synthesis method for granulation, which was conducive to exerting the phosphate adsorption capacity and facilitating practical application. The materials were characterized by SEM, EDX, XRD, BET, FTIR, and Zeta. In addition, the adsorption performance of La-MOFs/Al2O3 was evaluated through adsorption kinetics and isotherms, showing that the Langmuir adsorption capacity was 16.34 mgP·g-1 (25 °C) and increased with the water temperature. Moreover, the batch influence experiments of intimal pH, adsorbent dosage, coexisting ions, and stability tests were performed to analyze the potential for practical applications and verified through the natural micro-polluted water samples from Houxi River and Bailu Lake (China). The results indicated that the La-MOFs/Al2O3 was suited to a wide pH range of 4 to 10 and the phosphate removal efficiency remained above 70% after continuous use for four times, exhibiting excellent stability. It also had excellent selectivity in the presence of SO42-, Cl-, NO3-, and HCO3-, only decreased to 70.24% at high HCO3- ion concentration of 60 mg/L, respectively. And the La-MOFs/Al2O3 had excellent adsorption of total phosphorus, phosphate, and organic phosphorus in the actual river and lake water and completely removed dissolved phosphorus. Finally, a phosphate adsorption mechanism model involved in electrostatic interaction and ligand exchange was proposed. Therefore, La-MOFs/Al2O3 could be considered to be an excellent phosphorus adsorbent for application in the actual water environmental remediation.

QbD-Guided Traditional Chinese Medicine Manufacturing Process: Development and Optimization of Fluid-Bed Granulation and Drying Processes for Xiaochaihu Capsules.

Traditional methods of producing Xiaochaihu (XCH) capsules, a traditional Chinese medicine, are time-consuming, costly, and labor-intensive, which is not conductive to modernizing TCM. To address the challenges, new fluid-bed granulation and drying processes with water as the binder were developed and optimized guided by the principles of Quality by Design (QbD) in this study. Ishikawa diagram was applied to conduct a preliminary risk assessment, followed by 6-factor definitive screening design (DSD) serving as a QbD statistical tool to develop and optimize the new processes. Multiple potential factors and interactions were studied with a small number of experiments using the DSD. This study identified critical process parameters (CPPs), established quadratic regression models to reveal CPP-critical quality attributes (CQAs) connections within the DSD framework, and defined a dependable design space. Processes conducted by parameter combinations in the design space produced qualified granules with production yield and raw material utilization higher than 90% and moisture content lower than 4%. Furthermore, quantitative analysis of baicalin of all the granules ensured qualified contents of active pharmaceutical ingredient. The newly developed processes for XCH capsules, with advantages of shorter time, environmental friendliness, and decreased cost, exemplify the effective application of QbD and design of experiments (DoE) methodologies in the modernization of TCM manufacturing processes.

Predictive factors and clinical efficacy of Chinese medicine Shengji ointment in the treatment of diabetic foot ulcers in the elderly: a prospective study.

Objective: This study aims to investigate the predictive factors and efficacy of traditional Chinese medicine Shengji Ointment in the treatment of diabetic foot ulcers in the elderly population, with the intent of formulating an effective predictive model for deep diabetic foot ulcer healing. The importance of this research lies in its provision of new perspectives and tools for addressing the severe health impact of diabetic foot ulcers in the elderly population, considering the complexity and diversity of its treatment methods. Methods: The study includes 180 elderly patients with Wagner grade 3-4 diabetic foot ulcers that involve the tendon or fascia. The dependent variable is the initiation time of granulation tissue development. Independent variables encompass demographic information, a treatment strategy including Shengji Ointment, pre-treatment trauma assessment data, routine blood count, and biochemical index test results. Lasso regression is employed for variable selection, and Cox regression is utilized for the construction of a prediction model. A nomogram is generated to authenticate the model. Results: The Chinese Medicine treatment approach, ulcer location, creatinine levels, BMI, and haemoglobin levels are identified as independent predictors of granulation tissue development in diabetic foot ulcers. The combined treatment of Chinese herbal Shengji ointment and bromelain positively influenced granulation tissue development. The location of plantar ulcers, impaired renal functionality, obesity, and anaemia are established as independent risk factors that might influence the speed and probability of ulcer healing. The area under the time-dependent ROC curve fluctuates between 0.7 and 0.8, demonstrating substantial discrimination and calibration of the model. Conclusion: The study ascertains that a combined treatment strategy incorporating Shengji Ointment demonstrates greater effectiveness than the use of cleansing gel debridement alone in facilitating the healing of Wagner grade 3 or higher diabetic foot ulcers. Furthermore, the predictive model developed in this research serves as a valuable tool in evaluating the efficacy of Chinese Medicine treatments like Shengji Ointment for diabetic foot ulcers in the elderly. It aids clinicians in effectively assessing and adjusting treatment strategies, thereby proving its significant application value in clinical practice. Clinical Trial Registration: (https://www.chictr.org.cn/hvshowproject.html?id=73862&v=1.5&u_atoken=b403af53-d3b9-41ae-a7e2-db5498609b0c&u_asession=01tNh69p235bMUO4CmHIXcv8Hxirl5-557Duue9QB5lGfl3mf8IvPlcs2kN2zC30voX0KNBwm7Lovlpxjd_P_q4JsKWYrT3W_NKPr8w6oU7K_AyPrQhedMUWBMR2-ZDL_KO0uwDPR9XlF566xraDvT9mBkFo3NEHBv0PZUm6pbxQU&u_asig=05Kd_Q8fjv-24MVbZpOS9ef3xuCCN-tSVH5eUoJKgNLM7E0-n0zMpW6xLq9gh9aUhkKEEA15rdDoCydncF99APBwVSaTPgEG_V_B1iT4wimdCTxV_4ZVbTlDewxyQtE4YgU4-Oza7KPi94RJ64Utel0yZfqg3Tlm-bVxFNOY-zXFP9JS7q8ZD7Xtz2Ly-b0kmuyAKRFSVJkkdwVUnyHAIJzSYJ6SfhFl0WMTCCasZ7zV2I2qfyrp5m-SELPVeREKgX_6yRmLu26qT8kGfcS-Yaeu3h9VXwMyh6PgyDIVSG1W-7D_Sko5YQtpDbs3uvezYkZcUUY4o9-zDPaoYelmMDs8u7I4TPvtCXaPp44YUJcQ9bHr-_RmKA5V8nji3daArhmWspDxyAEEo4kbsryBKb9Q&u_aref=NNH1nHSUCE6pNvCilV%2F1MD0aERs%3D), identifier (ChiCTR2000039327).

Aerobic granular sludge formation and stability in enhanced biological phosphorus removal system under antibiotics pressure: Performance, granulation mechanism, and microbial successions.

Wastewater containing antibiotics can pose a significant threat to biological wastewater treatment processes. This study investigated the establishment and stable operation of enhanced biological phosphorus removal (EBPR) by aerobic granular sludge (AGS) under mixed stress conditions induced by tetracycline (TC), sulfamethoxazole (SMX), ofloxacin (OFL), and roxithromycin (ROX). The results show that the AGS system was efficient in removing TP (98.0%), COD (96.1%), and NH4+-N (99.6%). The average removal efficiencies of the four antibiotics were 79.17% (TC), 70.86% (SMX), 25.73% (OFL), and 88.93% (ROX), respectively. The microorganisms in the AGS system secreted more polysaccharides, which contributed to the reactor's tolerance to antibiotics and facilitated granulation by enhancing the production of protein, particularly loosely bound protein. Illumina MiSeq sequencing revealed that putative phosphate accumulating organisms (PAOs)-related genera (Pseudomonas and Flavobacterium) were enormously beneficial to the mature AGS for TP removal. Based on the analysis of extracellular polymeric substances, extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory, and microbial community, a three-stage granulation mechanism was proposed including adaption to the stress environment, formation of early aggregates and maturation of PAOs enriched microbial granules. Overall, the study demonstrated the stability of EBPR-AGS under mixed antibiotics pressure, providing insight into the granulation mechanism and the potential use of AGS for wastewater treatment containing antibiotics.

A new methodology of understanding the mechanism of high shear wet granulation based on experiment and molecular dynamics simulation.

In high shear wet granulation (HSWG), the interaction mechanism between binder and powder with different sugar content is still unclear. Herein, the law and mechanism of the interaction between binder and powder were studied on the molecular level by combining experiment analysis through the Kriging model and molecular dynamics (MD) simulation. For the sticky powder with high sugar content, the ethanol in the binder played a pivotal role in dispersing water into powders, and the amount of water determined the growth of granules. In the saturating stage, the reduction of sugar content facilitates the penetration of ethanol molecules. The concentration of ethanol determines whether the mixture is blended uniformly in the merging stage. The simulation results are consistent with the actual situation and explain the competition mechanism of interaction with binder and powder. Therefore, this research offers an efficient strategy for the in-depth understanding of the HSWG process where the powder is sticky, as well as providing guidelines for the practical application of preparation for Traditional Chinese Medicine (TCM) granules.

Combining biosolid and mineral sources of phosphorus and potassium in organomineral fertilizers influences the dynamics and efficiency of nutrient release.

Using urban residues to produce organomineral fertilizers (OMF) is an environmentally friendly strategy that can enhance soil fertility by adding organic matter and mineral nutrients. Herein we investigated the availability of N, P, and K, under organomineral fertilization in sandy soils. An incubation study was conducted using OMF formulated with biosolids as organic matrix and N source, rock phosphate, and potassium sulfate as P and K sources, respectively. Two forms of isolated N, P, and K sources (granulated and non-granulated), five N:P:K granulation proportions (1-2-0, 1-4-0, 1-0-2, 1-2-2, 1-2-4), and a control (unfertilized) were mixed with soil and assessed over a 112 days incubation period. Soil samples were collected at 0, 7, 14, 28, 56, and 112 days to quantify available soil concentrations of ammonium (N-NH4+), nitrate + nitrite (N-NO2- + N-NO3-), P, and K. The results showed that OMF formulated with NPK had better nitrogen efficiency indexes (NEI) than other formulations and did not induce N immobilization throughout the experiment. Regarding P and K efficiency, OMFs containing phosphorus and potassium increased the indexes compared to the single fertilizer sources. When comparing non-granulated potassium sulfate with granulated, the latter showed a steadier release due to the granulation process. In comparison with rock phosphate at the end of the experiment, the OMFs 1-2-0 and 1-4-2 had higher P available by 116 and 41%, respectively. Based on these results, OMFs have the potential to alter the dynamics of nutrient availability serving as a strategy for nutrient management in agriculture.

De novo granulation of sewage-borne microorganisms: A proof of concept on cultivating aerobic granular sludge without activated sludge and effective enhanced biological phosphorus removal.

Long start-up periods for granulating activated sludge and concerns on granular stability are the bottlenecks reported during implementation of novel aerobic granular sludge (AGS) technology in municipal wastewater treatment plants. Here, de novo granulation of sewage-borne microorganisms without using activated sludge (AS) inoculum was investigated in bench-scale sequencing batch reactors (SBR). Data showed that formation of AGS from sewage-borne microorganisms was rapid and first granules appeared within one week. Granulation was indicated by appearance of biomass particles (size >0.12 mm), high biomass levels (∼8 g/L) and superior settling properties (SVI30 min: 30 mL/g). Granulation process involved distinct stages like formation of aggregates, retention of aggregates, and growth of millimetre sized granules. Simultaneous COD, nitrogen and phosphorous removal was established within 10 days of start-up in the SBR without using AS inoculum. However, phosphorus removal became stable after 50 days of start-up. Total nitrogen (TN) and total phosphorus (TP) removals of 92% and 70%, respectively, were achieved from real domestic wastewater. Furthermore, addition of granular activated carbon (GAC) had improved both granulation and biological nutrient removals. Interestingly, phosphorus removal became quite stable within 10 days of start-up in the SBR operated with GAC particles. TN and TP removals were found to be higher at >98% and >94%, respectively, in GAC-augmented SBR. Removal of ammonia and phosphorus were mediated by nitritation-denitritation and enhanced biological phosphorus removal (EBPR) pathways, respectively. The bacterial diversity of AGS was lower than that of sewage. Quantitative PCR indicated enrichment of ammonia oxidizing bacteria, denitrifying bacteria and polyphosphate accumulating organisms during granulation. De novo granulation of sewage-borne microorganisms is a promising approach for rapidly cultivating AGS and establishing biological nutrient removal in sewage treatment plants.

Deep residual network enabled smart hyperspectral image analysis and its application to monitoring moisture, size distribution and contents of four bioactive compounds of granules in the fluid-bed granulation process of Guanxinning tablets.

Bed collapse is a serious problem in a fluid-bed granulation process of traditional Chinese medicine. Moisture content and size distribution are regarded as two pivotal influencing factors. Herein, a smart hyperspectral image analysis methodology was established via deep residual network (ResNet) algorithm, which was then applied to monitoring moisture content, size distribution and contents of four bioactive compounds of granules in the fluid-bed granulation process of Guanxinning tablets. First, a hyperspectral imaging camera was utilized to acquire hyperspectral images of 132 real granule samples in the spectral region of 389-1020 nm. Second, the moisture content and size distribution of the granules were measured with a laser particle sizer and a fast moisture analyzer, respectively. Moreover, the contents of danshensu, ferulic acid, rosmarinic acid and salvianolic acid B of the granules were determined by using high-performance liquid chromatography-diode array detection. Third, ResNet quantitative calibration models were built, which consisted of convolutional layer, maxpooling layer, four convolutional blocks with residual learning function and two fully connected layers. As a result, the Rc2 values for the moisture content, granule sizes and contents of four bioactive compounds are determined to be 0.957, 0.986, 0.936, 0.959, 0.937, 0.938, 0.956, 0.889, 0.914 and 0.928, whereas the Rp2 values are calculated as 0.940, 0.969, 0.904, 0.930, 0.925, 0.928, 0.896, 0.849, 0.844, and 0.905, respectively. The predicted values matched well with the measured values. These findings indicated that ResNet algorithm driven hyperspectral image analysis is feasible for monitoring both the physical and chemical properties of Guanxinning tablets at the same time.

[Key techniques for granulation and flavor masking of innovative Chinese medicinal preparations for children: a review].

There are many kinds of pharmaceutical preparations for children in China, which are generally divided into oral solid preparations and oral liquid preparations. Solid preparations, such as microtablets, pellets, dispersible tablets, and fine granules, have become the development trend of pediatric drugs. Liquid preparations mainly include syrup, suspension, oral solution, and drops. The poor taste and the treatment of drugs in children of different ages are the key factors affecting the efficacy, safety, and compliance of pediatric drugs. To reduce the risk caused by the fluctuation of blood concentration and improve the oral compliance of pediatric drugs, it is urgent to develop new techniques for granulation and flavor maskingto improve the poor taste of solid preparations. For liquid pre-parations with poor taste, the flavor correction technique should be used. This paper summarized the new pharmaceutical techniques for granulation and flavor masking, and it was found that sustained/controlled-releasegranules, fine granules, and chewing solid mini-tablets became the mainstream of oral solid preparations for children. Generally, multiparticle preparation, coating, microencapsulation, and other granulating techniques were involved in these preparations. Granulation and flavor masking are closely related and synergetic. Flavor masking techniques mask the bitter taste of Chinese medicine from four aspects, including confusing the brain taste, changing the compounds, reducing the exposure of bitter molecules to bitter receptors in the mouth, and numbing the taste cells to increase the threshold of bitter perception. At present, the main drugs for children on the market mainly inhibit the oral release of bitter drugs.

Effects of submicron magnetite particles on granulation of flocculent sludge and process stability in upflow anaerobic sludge blanket reactor.

Promoting direct interspecies electron transfer (DIET) with conductive additives is considered a promising approach to enhance methanogenesis. This study investigated the effects of adding submicron magnetite particles on sludge granulation and methanogenic performance in upflow anaerobic sludge blanket reactors inoculated with flocculent sludge. The reactor supplemented with magnetite was more stable and resilient than the no-magnetite control, with higher degree of granulation (up to 26.6-fold) and biomass retention. Magnetite addition to unstable reactors improved the methane yield in both reactors (1.2-1.3-fold). Electroactive Deltaproteobacteria bacteria, including Geobacter and Syntrophobacter, were enriched in the presence of magnetite. Methanogenic functional genes involved in DIET-based syntrophy were more abundant under magnetite-supplemented conditions. However, the improvement of methanogenic performance and granulation was limited, and inducing the self-embedment of magnetite into mature sludge granules rather than granulating flocculent sludge with magnetite appears to be a better strategy for engineering DIET in anaerobic granular sludge systems.

[Granulation of Yangxue Qingnao Granules in fluidized bed based on near-infrared spectroscopy].

To realize the real-time monitoring of the production process of Yangxue Qingnao Granules and improve the inter-batch consistency of granule quality in the granulation process, this study established a near-infrared quantitative prediction model of moisture, particle size, bulk density, and angle of repose in the fluidized bed granulation process of Yangxue Qingnao Granules based on near-infrared spectroscopy(NIRS). The near-infrared spectra were collected from 355 samples in 12 batches in the granulation process by integrating the sphere detection module of the near-infrared spectrometer. In combination with the pretreatment methods such as the first derivative, multiplicative scatter correction(MSC), and standard normal variate(SNV), the model was established by partial least squares(PLS) regression. The root mean square error of prediction(RMSEP) of moisture was 0.347 and R_P~2 was 0.935. The RMSEP of the D_(50) particle size model was 38.4 and R_P~2 was 0.980. The RMSEPs of bulk density and angle of repose were 0.018 8 and 0.879, with R_P~2 of 0.085 9 and 0.958. The results showed that the prediction of the PLS quantitative model combined with NIRS was accurate, and this model can be applied to the monitoring of key quality attributes in the fluidized bed granulation of Chinese medicinal granules in the production scale.

Effect of extrusion-spheronization granulation and manganese loading on catalytic ozonation of petrochemical wastewater.

The petrochemical secondary effluent (PSE) is typical refractory wastewater derived from the petrochemical industries, which requires advanced treatment due to the strict environmental protection policies. Catalytic ozonation is one of the most widely used advanced oxidation technologies in wastewater treatment because of its high mineralization rate, in which the alumina-based catalyst usually plays an important role. Extrusion-spheronization is a promising technique for the preparation of alumina spheres because the synthesized alumina particles have high sphericity, high specific surface aera and narrow particle size distribution. In this paper, two kinds of alumina-based catalysts (catalyst A: manganese nitrate added after alumina granulation and catalyst B: manganese nitrate added into alumina powder before granulation) were prepared by the extrusion-spheronization method and used for PSE treatment by catalytic ozonation. The prepared alumina samples were characterized by Brunauer-Emmett-Teller (BET) method, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and scanning electron microscopy (SEM), while the wastewater samples were analyzed for Total organic carbon (TOC), UV254 and fluorescence spectroscopy. Results showed that manganese was uniformly distributed in both catalysts, and the specific surface area of two catalysts was 318.36 m2/g and 354.95 m2/g, respectively. Catalytic ozonation experiments were repeated nine times with each catalyst under the same conditions. The TOC removal rates for catalysts A and B in the first run were 48.88% and 49.06%, respectively, then it dropped to 28.05% for catalyst A but remained 47.81% for catalyst B after using for nine times. This implied that the long-term performance of catalyst B would be more stable than catalyst A. Similar result were found in three-dimensional fluorescence analysis. UV254 results indicated that the removal efficiency of aromatic and unsaturated substances by catalyst B was higher than catalyst A. A possible explanation is that the active component manganese oxide formed a catalyst skeleton in catalyst B, which makes it hard to dissolve. Effect of extrusion-spheronization granulation and manganese loading on advanced oxidant treatment of petrochemical wastewater.

[Prediction of formability of flavonoid extract granules by dry granulation based on design space and RBFNN].

In this paper, a flavonoid extract powder properties-process parameters-granule forming rate prediction model was constructed based on design space and radial basis function neural network(RBFNN) to predict the formability of flavonoid extract gra-nules. Box-Behnken experimental design was employed to explore the mathematical relationships between critical process parameters and quality attributes. The design space of critical process parameters was developed, and the accuracy of the design space was verified by Monte Carlo method(MC). Design Expert 10 was used for Box-Behnken design and mixture design. Scutellariae Radix mixed powder was prepared and its powder properties were measured. The mixed powder was then subjected to dry granulation and the granule forming rate was determined. The correlations between powder properties were analyzed by variance influence factor(VIF), and principal component analysis(PCA) was performed for the factors with strong collinearity. In this way, a prediction model of powder properties-process parameters-granule forming rate was established based on RBFNN, the accuracy of which was evaluated with examples. The results showed that the model had a good predictive effect on the granule forming rate, with the average relative error of 1.04%. The predicted value and the measured value had a high degree of fitting, which indicated that model presented a good prediction ability. The prediction model established in this study can provide reference for the establishment of quality control methods for Chinese medicinal preparations with similar physical properties.

Impact of primary sedimentation on granulation and treatment performance of municipal wastewater by aerobic granular sludge process.

Aerobic granules contain microorganisms that are responsible for carbon, nitrogen, and phosphorus removal in aerobic granular sludge (AGS) process in which aerobic/anoxic/anaerobic layers (from surface to core) occur in a single granule. Optimizing the aerobic granular sludge (AGS) process for granulation and efficient nutrient removal can be challenging. The aim of this study was to examine the impact of settling prior to AGS process on granulation and treatment performance of the process. For this purpose, synthetic wastewater mimicking municipal wastewater was fed directly (Stage 1), and after primary sedimentation (Stage 2) to a laboratory-scale AGS system. In full-scale wastewater treatment plants, primary sedimentation is used to remove particulate organic matter and produce primary sludge which is sent to anaerobic digesters to produce biogas. Performances obtained in both stages were compared in terms of treatment efficiency, granule settling behavior, and granule morphology. Granulation was achieved in both stages with more than 92% chemical oxygen demand (COD) removal efficiencies in each stage. High nutrient removal was obtained in Stage 1 since anaerobic phase was long enough (i.e., 50 min) to hydrolyze particulate matter to become available for PAOs. Primary sedimentation caused a decrease in influent organic load and COD/N ratio, as a result, low nitrogen and phosphorus removal efficiencies were observed in Stage 2 compared to Stage 1. With this study, the effect of the primary sedimentation on the biological removal performance of AGS process was revealed. COD requirement for nutrient removal in AGS systems should be assessed by considering energy generation via biogas production from primary sedimentation sludge.

Supraphysiological testosterone supplementation improves granulation tissue maturation through angiogenesis in the early phase of a cutaneous wound healing model in rats.

OBJECTIVE: The aim of this study was to evaluate the effects of both testosterone depletion and supraphysiological testosterone supplementation in the early phase of an animal cutaneous wound healing model in comparison with the physiological hormonal condition. MATERIAL AND METHODS: Forty rats were distributed into the following four groups: Control, Orchiectomy (OCX), Durateston (Dura) and OCX+Dura. On day 1, the testicles were removed (OCX group) and the rats (Dura group) received a supraphysiological dose (250 mg/kg) of exogenous testosterone weekly. After 15 days a full-thickness excisional skin wound was created in all animals, which was healed by the second intention for 7 days. On day 22, the rats were euthanatized and the wounds were harvested for histopathological evaluation, immunohistochemistry analyses and multiplex immunoassay. One-way ANOVA and post-hoc Tukey tests were performed. RESULTS: It was found that the supraphysiological testosterone level increased extracellular matrix deposition, promoted higher blood vessel formation and reduced wound contraction (p < 0.05). Additionally, it also stimulated PCNA-positive fibroblasts and KGF-positive cells (p < 0.05), while orchiectomy reduced the expression of IL-6 and TNF-α and increased VEGF and PDGF (p < 0.05) . CONCLUSION: In conclusion, the results provide evidence that supraphysiological testosterone supplementation plays a positive role in the early phase of cutaneous wound healing, thus improving granulation tissue maturation through the enhancement of angiogenesis.

A Systematic Review of the Effect of Centella asiatica on Wound Healing.

BACKGROUND: Under metabolic stress conditions, there is a higher demand for nutrients which needs to be met. This is to reduce the risk of delay in wound healing which could lead to chronic wound. AIM: This is a systematic review of the effect of Centella asiatica on wound healing. C. asiatica is a traditional medicinal plant used due to its antimicrobial, antioxidant, anti-inflammatory, neuroprotective, and wound healing properties. METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for the systematic review and four electronic databases were used. RESULTS: Four clinical trials met the inclusion criteria. The following distinct areas were identified under C. asiatica: wound contraction and granulation; healing/bleeding time and re-epithelialization; VAS (visual analogue scale) scores; skin erythema and wound appearance. CONCLUSIONS: C. asiatica might enhance wound healing resulting from improved angiogenesis. This might occur due to its stimulating effect on collagen I, Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) production. Besides, C. asiatica has shown an anti-inflammatory effect observed by the reduction in Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) and Tumour Necrosis Factor α (TNFα), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), and lipoxygenase (LOX) activity. Delivery systems such as nanoencapsulation could be used to increase C. asiatica bioavailability. Nevertheless, more studies are needed in order to perform a meta-analysis and ascertain the effects of C. asiatica on wound healing and its different parameters.

Enhanced aerobic granulation for treating low-strength wastewater in an anaerobic-aerobic-anoxic sequencing batch reactor by selecting slow-growing organisms and adding carriers.

The aerobic granular sludge (AGS) process is a promising technology for wastewater treatment. However, a long start-up period for granulation and instability during long-term operation still hinder the application of AGS technology, especially for low-strength wastewater. To solve these two problems, this study tested a novel strategy involving the selection of slow-growing organisms and the addition of carriers in an anaerobic-aerobic-anoxic sequencing batch reactor (AN/O/AX_SBR). Three identical AN/O/AX_SBRs (R_Ctrl, R_CCM, and R_GAC), fed with low-strength wastewater, were operated for 120 days. R_Ctrl had no carriers, R_CCM contained cell culture microcarriers (CCM), and R_GAC contained granular activated carbon (GAC). Mature AGS was achieved within 80 days in all reactors. The carriers could reduce the maturation period of AGS by approximately 10 days (76, 66, and 69 days in R_Ctrl, R_CCM, and R_GAC, respectively) and improve the physical strength of the AGS. AGS showed a strong structure without excessive proliferation of filamentous bacteria, full-grown size (900-1100 µm), and good settleability (SVI5 was 15.4-19.4 mL/g). Microbiological analysis showed that AN/O/AX_SBRs can provide a metabolic selective pressure to select slow-growing organisms such as nitrifying bacteria (norank_f__NS9_marine_group, Ellin6067, and Nitrospira), glycogen and phosphorus accumulating organisms (GAOs: Candidatus_Competibacter and Defluviicoccus; PAOs: Candidatus_Accumulibacter and Flavobacterium). All reactors showed good performance for simultaneous nitrification, endogenous denitrification, and phosphorus removal. The removal efficiencies of total nitrogen and total phosphorous were above 70% and 80%, respectively. The cycle test showed intermediate PAO-GAO metabolism prevailed in the system, and endogenous denitrification was primarily carried out by denitrifying GAOs.

Microstructure and granulation cycle mechanisms of anammox-HAP coupled granule in the anammox EGSB reactor.

The formation of anammox-hydroxyapatite (HAP) coupled granules has been shown to be an approach to efficient nitrogen removal and phosphorus recovery in the anammox EGSB reactor. However, the granulation cycle mechanism of anammox-HAP coupled granules for sustainable regeneration and growth is still not well understood. In this study, the microstructure, chemical composition and microbial structure of a total of six different-sized granules, from 0.25 mm to 2.8 mm, was determined. An SEM-EDS analysis indicated that the small granules (<0.5 mm) were composed of poly-pellet clusters with anammox biofilms attached to the HAP cores, and the large granules (>0.5 mm) consisted of a three-layer structure: a surface anammox biofilm layer, a middle connection layer, and a HAP mineral inner core. The analysis of elemental composition and microbial structure suggested homogenous granular characteristics regardless of granule size. The dominant microorganisms were anammox bacteria of Candidatus Kuenenia stuttgartiensis and heterotrophic denitrifying bacteria. Based on these results, a granulation cycle mechanism for anammox-HAP coupled granules was proposed for the first time. The growth of the small granules with the simultaneous enlargement of anammox biofilms and HAP cores results in the formation of large granules. Large granules regenerate new small granules in a two-step procedure. The first step is the separation of embryo HAP crystals from the mother core via heterogeneous growth, and the second step is the separation of the biofilms due to biodegradation and shear stress.