An integrated in silico approach for the identification of novel potential drug target and chimeric vaccine against Neisseria meningitides strain 331401 serogroup X by subtractive genomics and reverse vaccinology.

Neisseria meningitidis, commonly known as the meningococcus, leads to substantial illness and death among children and young adults globally, revealing as either epidemic or sporadic meningitis and/or septicemia. In this study, we have designed a novel peptide-based chimeric vaccine candidate against the N. meningitidis strain 331,401 serogroup X. Through rigorous analysis of subtractive genomics, two essential cytoplasmic proteins, namely UPI000012E8E0(UDP-3-O-acyl-GlcNAc deacetylase) and UPI0000ECF4A9(UDP-N-acetylglucosamine acyltransferase) emerged as potential drug targets. Additionally, using reverse vaccinology, the outer membrane protein UPI0001F4D537 (Membrane fusion protein MtrC) identified by subcellular localization and recognized for its known indispensable role in bacterial survival was identified as a novel chimeric vaccine target. Following a careful comparison of MHC-I, MHC-II, T-cell, and B-cell epitopes, three epitopes derived from UPI0001F4D537 were linked with three types of linkers-GGGS, EAAAK, and the essential PADRE-for vaccine construction. This resulted in eight distinct vaccine models (V1-V8). Among them V1 model was selected as the final vaccine construct. It exhibits exceptional immunogenicity, safety, and enhanced antigenicity, with 97.7 % of its residues in the Ramachandran plot's most favored region. Subsequently, the vaccine structure was docked with the TLR4/MD2 complex and six different HLA allele receptors using the HADDOCK server. The docking resulted in the lowest HADDOCK score of 39.3 ± 9.0 for TLR/MD2. Immune stimulation showed a strong immune response, including antibodies creation and the activation of B-cells, T Cytotoxic cells, T Helper cells, Natural Killer cells, and interleukins. Furthermore, the vaccine construct was successfully expressed in the Escherichia coli system by reverse transcription, optimization, and ligation in the pET-28a (+) vector for the expression study. The current study proposes V1 construct has the potential to elicit both cellular and humoral responses, crucial for the developing an epitope-based vaccine against N. meningitidis strain 331,401 serogroup X.

Advancements on the impact of hydroxychloroquine in systemic lupus erythematosus.

Hydroxychloroquine (HCQ) has gained significant attention as a therapeutic option for systemic lupus erythematosus (SLE) because of its multifaceted mechanism of action. It is a lipophilic, lysosomotropic drug, that easily traverses cell membranes and accumulates in lysosomes. Once accumulated, HCQ alkalizes lysosomes within the cytoplasm, thereby disrupting their function and interfering with processes like antigen presentation. Additionally, HCQ has shown potential in modulating T-cell responses, inhibiting cytokine production, and influencing Toll-like receptor signaling. Its immunomodulatory effects have generated interest in its application for autoimmune disorders. Despite its established efficacy, uncertainties persist regarding the optimal therapeutic concentrations and their correlation with adverse effects such as retinal toxicity. Therefore, standardized dosing and monitoring guidelines are crucial. In this study, we provide a comprehensive review of the mechanisms, efficacy, dosing variations, and retinal toxicity profiles of HCQ, which are essential to optimize SLE treatment protocols and ensure patient safety.

Digital Therapy for Visual Acuity and Binocular Function in Children with Anisometropic Amblyopia.

Amblyopia affects development of children's monocular vision and binocular function and becomes a largely intractable problem with increasing aging. This study is to investigate the binocular function and evaluate efficacy of digital therapy in children 8-13 years of age with anisometropic amblyopia. The patients in the digital therapy group performed the training with the digital amblyopia therapeutic software. The visual acuity and binocular function (perceptual eye position [PEP], suppression, and stereopsis) were examined at the first visit and 3-month post-treatment. Twenty-three cases in the control group and 25 cases in the digital therapy group were enrolled. The results revealed that 3-month digital therapy can effectively improve corrected distance visual acuity (CDVA) and improve the binocular function, including PEP, suppression, and second-order stereopsis in children with anisometropic amblyopia, 8-13 years of age. Digital therapy for amblyopia can effectively improve monocular CDVA of amblyopic eyes and binocular function in older children with anisometropic amblyopia.

The effects of sex hormones during the menstrual cycle on knee kinematics.

The effects of the menstrual cycle and sex hormones on knee kinematics remain unclear. The purpose of the study was to investigate the effects of the menstrual cycle and serum sex hormone concentrations on knee kinematic parameters of the 90°cutting in female college soccer athletes. Three female college soccer teams (53 subjects) participated in the study. During the first menstrual cycle, a three-step method was used to exclude subjects with anovulatory and luteal phase-deficient (LPD) (12 subjects). The subjects' menstrual cycle was divided into the menstrual phase, late-follicular phase, ovulatory phase, and mid-luteal phase (group 1, 2, 3, 4). In each phase of the second menstrual cycle, we used a portable motion analysis system to enter the teams and tested the sex hormones concentrations and knee kinematics parameters in three universities in turn. We found that subjects had a lower maximum knee valgus in group 4 compared with other groups. This meant that subjects had a lower biomechanical risk of non-contact anterior cruciate ligament (ACL) injury in the mid-luteal phase. There was no significant correlation between serum estrogen, progesterone concentration, and knee kinematic parameters. This meant that sex hormones did not have a protective effect. Future studies need to incorporate more factors (such as neuromuscular control, etc.) to investigate.

Effects of epigallocatechin gallate, caffeine, and their combination on fat accumulation in high-glucose diet-fed Caenorhabditis elegans.

Epigallocatechin gallate (EGCG) and caffeine are inevitable to be ingested together in the process of drinking green tea. This study used Caenorhabditis elegans as an organism model to examine whether the binding of EGCG and caffeine could influence the fat-reduction effect. The results revealed that EGCG significantly reduced the Nile Red fluorescence intensity and the triglyceride/protein ratio of the C. elegans obesity model by 14.7% and 16.5%, respectively, while the effect of caffeine was not significant. Moreover, the degree of reduction in fluorescence intensity and triglyceride/protein ratio by EGCG + caffeine was comparable to that of EGCG. In the exploration of underlying mechanism, we found that EGCG and EGCG + caffeine treatments had no influence on food intake and energy expenditure of C. elegans. Their fat-reduction effects were dependent on the regulation of lipogenesis, as shown by the decreased expression of the sbp-1, fat-7, and daf-16 genes.

Structure bionic topology design method based on biological unit cell.

The mechanical structure topology design based on substructure always adopts the traditional substructure design method, which often comes from the experience and is limited by the inherent or stereotyped design thinking. A substructure design method based on biological unit cell (UC) is proposed, which draws inspiration from the biological efficient load-bearing topology structure. Especially, the thought of the formalized problem-solving of extension matter-element is introduced. Through the matter-element definition of UC substructure, the process model for the structure bionic topology design method based on biological UC is formed, which avoids the random or wild mental stimulation of the structure topology design method based on traditional substructure. In particular, in this proposed method, aiming at the problem about how to achieve the integration of high-efficiency load-bearing advantage of different organisms, furthermore, a biological UC hybridization method based on the principle of inventive problem solving theory (TRIZ) is proposed. The typical case is used to illustrate the process of this method in detail. The results from simulations and experiments both show that: the load-bearing capacity of structure design based on biology UC is improved than the initial design; on this basis, the load-bearing capacity of structure design is improved further through UC hybridization. All these show the feasibility and correctness of the proposed method.

Multi-stable isotope and multi-element origin traceability of rice from the main producing regions in Asia: A long-term investigation during 2017-2020.

Stable isotope and multi-element analytical techniques with chemometrics were developed to trace the origin authenticity of rice in China market. In the long-term study from 2017 to 2020, a total of 115 batches of rice samples from 8 main producing areas of 7 Asian countries were determined 5 stable isotope ratios and 18 elemental contents. One-way analysis of variance (ANOVA) and various multivariate modeling methods were performed for the origin discrimination. Supervised multivariate modeling including partial least squares discriminant analysis (PLS-DA) and linear discriminant analysis (LDA) can realize more satisfactory identification of 8 rice origins than ANOVA comparison and unsupervised methods, their leave-one-out cross-validation accuracies approach 85.0 % and 90.9 %, respectively. δ2H, δ13C, Ba, Al, Mg, δ34S, Pb and δ18O were screened as the most important variables for rice origin traceability (VIP > 1 or AUC > 0.5). This analytical strategy combining maybe promising to ensure the origin authenticity and combat illegal mislabeling in rice trade.

A new oleanane-type triterpene from Ardisia lindleyana D.Dietr and its cytotoxic activity.

A new oleanane-type triterpene, ardisiapunine A (1), together with eight known compounds were isolated from the roots of Ardisia lindleyana D.Dietr. Their chemical structures were determined by means of spectroscopic methods including HR-ESI-MS and (1 D, 2 D) NMR data. The absolute configuration of compound 1 was established by a single-crystal X-ray diffraction experiment. The new compound is an unusual oleanane-type triterpene bearing an acetal and a C-13-C-18 double bond. The cytotoxicity of all isolated compounds were evaluated using four human cancer cell lines, including A549, HepG2, HeLa and U87. The new compound 1 and compound 2 were weakly active but the known compound 6 exhibited a high cytotoxicity compared to cisplatin.

Purification of total flavonoids from Ginkgo biloba flowers with resin column chromatography and evaluation of antioxidant activities in vitro.

Purification of total flavonoids from Ginkgo biloba flowers (GBF) extracts were studied using six resins. Adsorption-desorption experiments indicated that polyamide resin is the most suitable resin. The optimal purification process of total flavonoids of GBF was as follows: a loading concentration of 5.85 mg/mL, a loading volume of 1 bed volume (BV), a loading flow rate of 2 BV/h, a water volume of 2.67 BV, and a desorption solution of 40% ethanol. Under these conditions, the maximum purity of total flavonoids was 37.1 ± 1.1%. The antioxidant activity of purified flavonoids was further evaluated in vitro. It showed that the 40% ethanol purified fraction (Fr. B) group had the strongest antioxidant activity of the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity concentration for 50% of maximal effect (EC50, 145.4 ± 13.8 µg/mL) and ferric reducing ability (2.5 ± 0.2 mM FeSO4 equivalent mg-1 Fr. B). In addition, at the concentration of 160 µg/mL, the Fr. B strikingly increased the viability rate of hydrogen peroxide stimulated PC-12 cells to normal levels (***p < 0.001). This method provides a basis for the application and development of GBF resources. It indicated that the purified GBF flavonoids can be used as a source of potential antioxidant.

Cognitive changes are associated with increased blood-brain barrier leakage in non-brain metastases lung cancer patients.

To explore the relationship between cognitive function and blood-brain barrier leakage in non-brain metastasis lung cancer and healthy controls. 75 lung cancers without brain metastasis and 29 healthy controls matched with age, sex, and education were evaluated by cognitive assessment, and the Patlak pharmacokinetic model was used to calculate the average leakage in each brain region according to the automated anatomical labeling atlas. After that, the relationships between cognitive and blood-brain barrier leakage were evaluated. Compared with healthy controls, the leakage of bilateral temporal gyrus and whole brain gyrus were higher in patients with lung cancers (P < 0.05), mainly in patients with advanced lung cancer (P < 0.05), but not in patients with early lung cancer (P > 0.05). The cognitive impairment of advanced lung cancers was mainly reflected in the damage of visuospatial/executive, and delayed recall. The left temporal gyrus with increased blood-brain barrier leakage showed negative correlations with delayed recall (r = -0.201, P = 0.042). An increase in blood-brain barrier leakage was found in non-brain metastases advanced lung cancers that corresponded to decreased delayed recall. With progression in lung cancer staging, blood-brain barrier shows higher leakage and may lead to brain metastases and lower cognitive development.

Optimal Energy Management System of IoT-Enabled Large Building Considering Electric Vehicle Scheduling, Distributed Resources, and Demand Response Schemes.

In the energy system, various sources are used to fulfill the energy demand of large buildings. The energy management of large-scale buildings is very important. The proposed system comprises solar PVs, energy storage systems, and electric vehicles. Demand response (DR) schemes are considered in various studies, but the analysis of the impact of dynamic DR on operational cost has been ignored. So, in this paper, renewable energy resources and storages are integrated considering the demand response strategies such as real-time pricing (RTP), critical peak pricing (CPP), and time of use (ToU). The proposed system is mapped in a linear model and simulated in MATLAB using linear programming (LP). Different case studies are investigated considering the dynamic demand response schemes. Among different schemes, results based on real-time pricing (58% saving) show more saving as compared to the CPP and ToU. The obtained results reduced the operational cost and greenhouse gas (GHG) emissions, which shows the efficacy of the model.

Chemical constituents from the aerial parts of Orychophragmus violaceus.

A new alkaloid, demethylorychophragine A (1), together with 18 known compounds was isolated from the aerial parts of Orychophragmus violaceus. Structure of the new compound was identified by extensive spectroscopic techniques. 2 and 3 were isolated from nature for the first time. Known compounds were identified by comparison with data reported in the literature. All compounds were evaluated for anti-radiation activities against X-ray irradiation in HUVEC cell line. Results showed that 10, 12, and 15 showed excellent anti-radiation activity. All compounds were tested for cytotoxic activity against SH-SY5Y and HeLa cell lines. 16 exhibited significant cytotoxicity activity against SH-SY5Y cells, with IC50 value of 23.86 ± 0.38 µM (p = 0.045). The anti-inflammatory effects of all compounds were assessed by determining their ability to inhibit the production of NO, which was induced by stimulating the RAW264.7 murine macrophage cell line with lipopolysaccharide. 16 markedly decreased NO to a level of 27.34 ± 1.29 µM.

Biodegradable Silk Fibroin Nanocarriers to Modulate Hypoxia Tumor Microenvironment Favoring Enhanced Chemotherapy.

Biopolymer silk fibroin (SF) is a great candidate for drug carriers characterized by its tunable biodegradability, and excellent biocompatibility properties. Recently, we have constructed SF-based nano-enabled drug delivery carriers, in which doxorubicin (Dox) and atovaquone (Ato) were encapsulated with Arg-Gly-Asp-SF-Polylactic Acid (RSA) to form micellar-like nanoparticles (RSA-Dox-Ato NPs). The RGD peptide was decorated on micellar-like nanoparticles, promoting tumor accumulation of the drug. Meanwhile, Ato, as a mitochondrial complex III inhibitor inhibiting mitochondrial respiration, would reverse the hypoxia microenvironment and enhance chemotherapy in the tumor. In vitro, the biopolymer alone showed extremely low cytotoxicity to 4T1 cell lines, while the RSA-Dox-Ato demonstrated a higher inhibition rate than other groups. Most significantly, the ROS levels in cells were obviously improved after being treated with RSA-Dox-Ato, indicating that the hypoxic microenvironment was alleviated. Eventually, SF-based targeted drug carrier provides biocompatibility to reverse hypoxia microenvironment in vivo for enhancing chemotherapy, strikingly suppressing tumor development, and thereby suggesting a promising candidate for drug delivery system.

Scheduling and Sizing of Campus Microgrid Considering Demand Response and Economic Analysis.

Current energy systems face multiple problems related to inflation in energy prices, reduction of fossil fuels, and greenhouse gas emissions which are disturbing the comfort zone of energy consumers and the affordability of power for large commercial customers. These kinds of problems can be alleviated with the help of optimal planning of demand response policies and with distributed generators in the distribution system. The objective of this article is to give a strategic proposition of an energy management system for a campus microgrid (µG) to minimize the operating costs and to increase the self-consuming energy of the green distributed generators (DGs). To this end, a real-time based campus is considered that currently takes provision of its loads from the utility grid only. According to the proposed given scenario, it will contain solar panels and a wind turbine as non-dispatchable DGs while a diesel generator is considered as a dispatchable DG. It also incorporates an energy storage system with optimal sizing of BESS to tackle the multiple disturbances that arise from solar radiation. The resultant problem of linear mathematics was simulated and plotted in MATLAB with mixed-integer linear programming. Simulation results show that the proposed given model of energy management (EMS) minimizes the grid electricity costs by 668.8 CC/day ($) which is 36.6% of savings for the campus microgrid. The economic prognosis for the campus to give an optimum result for the UET Taxila, Campus was also analyzed. The general effect of a medium-sized solar PV installation on carbon emissions and energy consumption costs was also determined. The substantial environmental and economic benefits compared to the present situation have prompted the campus owners to invest in the DGs and to install large-scale energy storage.

Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders?

Neuroinflammatory disorder is a general term that is associated with the progressive loss of neuronal structure or function. At present, the widely studied diseases with neuroinflammatory components are mainly divided into neurodegenerative and neuropsychiatric diseases, namely, Alzheimer's disease, Parkinson's disease, depression, stroke, and so on. An appropriate neuroinflammatory response can promote brain homeostasis, while excessive neuroinflammation can inhibit neuronal regeneration and damage the central nervous system. Apart from the symptomatic treatment with cholinesterase inhibitors, antidepressants/anxiolytics, and neuroprotective drugs, the treatment of neuroinflammation is a promising therapeutic method. Sirtuins are a host of class III histone deacetylases, that require nicotinamide adenine dinucleotide for their lysine residue deacetylase activity. The role of sirtuin 2 (SIRT2), one of the sirtuins, in modulating senescence, myelin formation, autophagy, and inflammation has been widely studied. SIRT2 is associated with many neuroinflammatory disorders considering it has deacetylation properties, that regulate the entire immune homeostasis. The aim of this review was to summarize the latest progress in regulating the effects of SIRT2 on immune homeostasis in neuroinflammatory disorders. The overall structure and catalytic properties of SIRT2, the selective inhibitors of SIRT2, the relationship between immune homeostasis and SIRT2, and the multitasking role of SIRT2 in several diseases with neuroinflammatory components were discussed.

A randomized, parallel control and multicenter clinical trial of evidence-based traditional Chinese medicine massage treatment VS External Diclofenac Diethylamine Emulgel for the treatment of knee osteoarthritis.

BACKGROUND: Both massage and topically administered NSAIDs are safe and effective treatments for knee osteoarthritis (KOA); however, different massage technique sects in China caused assessment difficulties for the treatment of KOA. In order to standardize the massage techniques and procedures, we organized multi-disciplinary experts in China to acquire an evidence-based traditional Chinese medicine massage treatment of knee osteoarthritis. The purposes of this study will be to provide clinicians a complementary and alternative therapy for patients and to evaluate the efficacy and safety of evidence-based traditional Chinese medicine massage treatment of KOA compared to External Diclofenac Diethylamine Emulgel. METHODS AND DESIGN: A randomized controlled trial in which 300 participants diagnosed with KOA will be recruited and randomly allocated to either the experimental group or the control group in a ratio of 2:1. Two hundred participants will receive evidence-based traditional Chinese medicine massage 2 sessions per week for 10 weeks as the experimental group, and 100 participants will receive External Diclofenac Diethylamine Emulgel 3-4 times per day for 10 weeks as the control group. The patients in the two groups will receive follow-up at two time points at 5 weeks and 10 weeks from the beginning of treatment, respectively. The MRI scans and X-ray will be performed at baseline and at the end of the intervention. The primary outcome will be the changes in the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Secondary outcomes will be measured by the PRO scale for knee osteoarthritis based on the concept of traditional Chinese medicine (Chinese scale for knee osteoarthritis (CSKO)), X-ray evaluation, and MRI scan evaluation. The data of WOMAC and CSKO will be analyzed at the baseline, 5 weeks, and 10 weeks from the beginning of treatment. The data from MRI scans and X-rays will be analyzed at baseline and at the end of the intervention. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session. DISCUSSION: This study will provide clinicians with much-needed knowledge for the treatment of KOA through a controlled trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800014400 . Registered on 10 January 2018.

Does more voluntary environmental information disclosure cut down the cost of equity: heavy pollution industries in China.

Examining the coexisting policies for mandatory and voluntary disclosure of environmental information, this paper focuses on the unique background for such disclosure in the context of domestic companies in heavy pollution industries (EHPIs), a topic thus far overlooked by the literature. We aim to identify, in regard to compulsory environmental information disclosure in financial reports, whether adding further voluntary information disclosure to corporate social responsibility (CSR) results in an extra discount from investors during an equity financing. We evaluate a sample of 4390 A-share listed companies in EHPIs operating in China between 2010 and 2018. Specifically, linguistic analysis and image recognition are conducted with Python, and a regression model is applied to test our hypotheses. The positive impact of the following variables on the cost reduction in equity capital is thus demonstrated: (a) CSR disclosure, (b) higher quality CSR reports, (c) increased environmental information disclosure in CSR reports (CSR_E), (d) more accurate environmental investment information, and (e) additional graphs and text. Moreover, the degree of CSR_E disclosure's reduction in the cost of equity is 30 times that of CSR disclosure, while charts have specific positive effects that text does not. Therefore, we identify a new path for remitting information asymmetry in a financial market by extending information manipulation research, especially studies of nonfinancial information. Overall, information disclosure should be taken seriously by both firms and supervisors. Hence, this study offers guidelines for regulatory authorities to explore the coordination effect of mandatory and voluntary disclosure policies, i.e., to achieve environmental governance and the sustainable development of enterprises by improving corporate governance.

Research on anthracnose grade of Camellia oleifera based on the combined LIBS and THz technology.

BACKGROUND: Anthracnose of Camellia oleifera is a very destructive disease that commonly occurs in the Camellia oleifera industry, which severely restricts the development of the Camellia oleifera industry. In the early stage of the Camellia oleifera suffering from anthracnose, only the diseased parts of the tree need to be repaired in time. With the aggravation of the disease, the diseased branches need to be eradicated, and severely diseased plants should be cut down in time. At present, aiming at the problems of complex experiments and low accuracy in detecting the degree of anthracnose of Camellia oleifera, a method is proposed to detect the degree of anthracnose of Camellia oleifera leaves by using terahertz spectroscopy (THz) combined with laser-induced breakdown spectroscopy (LIBS), so as to realize the rapid, efficient, non-destructive and high-precision determination of the degree of anthracnose of Camellia oleifera. RESULTS: Mn, Ca, Ca II, Fe and other elements in the LIBS spectrum of healthy and infected Camellia oleifera leaves with different degrees of anthracnose are significantly different, and the Terahertz absorption spectra of healthy Camellia oleifera leaves, and Camellia oleifera leaves with different degrees of anthracnose there are also significant differences. Partial least squares discriminant analysis (PLS-DA), support vector machine (SVM), and linear discriminant analysis (LDA) are used to establish the fusion spectrum anthracnose classification model of Camellia oleifera. Among them, the Root mean square error of prediction (RMSEP) and the prediction determination coefficient R2p of THz-LIBS-CARS-PLS-DA of prediction set are 0.110 and 0.995 respectively, and the misjudgment rate is 1.03%; The accuracy of the modeling set of THz (CARS)-LIBS (CARS)-SVM is 100%, and the accuracy of prediction set is 100%, after preprocessing of the multivariate scattering correction (MSC), the accuracy of the THz-LIBS-MSC-CARS modeling set is 100%, and the accuracy of prediction set is 100%; The accuracy rate of THz-LIBS-MSC-CARS-LDA of modeling set is 98.98%, and the accuracy rate of the prediction set is 96.87%. CONCLUSION: The experimental results show that: the SVM model has higher qualitative analysis accuracy and is more stable than the PLS-DA and LDA models. The results showed that: the THz spectrum combined with the LIBS spectrum could be used to separate healthy Camellia oleifera leaves from various grades of anthracnose Camellia oleifera leaves non-destructively, quickly and accurately.

Study on the action mechanism of the peptide compounds of Wuguchong on diabetic ulcers, based on UHPLC-Q-TOF-MS, network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic foot ulcers mainly refer to people who are initially diabetic and do not have peripheral neuropathy or peripheral vascular disease, but have developed foot infection, septicemia, and ulceration. Diabetic trauma disease is characterized by high sugar and very slow wound healing, which is the reason why some patients with severe diabetic trauma require amputation. Prolonged hyperglycemia can lead to changes in bodily functions and endocrine changes, which can lead to permeability damage of epidermal tissue structure, microvascular damage and, in more severe cases, nerve damage, which are also the main causes of diabetic trauma. Small molecule peptides have various biological activities, such as: lowering blood pressure, antibacterial and wound healing activities, etc. It is a drug recorded in classical Chinese medicine, it is safer to use natural active peptides to treat wounds compared to the listed drugs, and there are no side effects in its use.The wound healing effect of Wuguchong dry product has been confirmed but the mechanism is still unclear, whether it is related to the small molecule active peptides contained in it remains to be studied. AIM OF STUDY: Objective To investigate the potential mechanism of the peptide compounds of Wuguchong (PCW) on diabetic wound healing and the relevant targets in the pathway associated with the treatment of diabetic ulcers using a systematic pharmacological and pharmacological experimental validation approach. METHODS: 1) PCW was prepared by enzymatic digestion of TCMW and analyzed by UHPLC-Q-TOF-MS. 2) Further screening of the active chemical components of PCW using PubChem, Swiss Target Prediction data. 3) Prediction of its targets using Drug Bank, CTD, and Genecards databases. 4) Construct protein/gene interactions network diagrams for PCWs acting by using Cytoscape 3.7.0 software. 5) GO and KEGG analysis of PCW targets were performed by David database. 6) Validated by AO/EB staining, scratching and in vitro tube formation methods. 7) Explored the mechanism of PCW to promote diabetic wound healing by protein blotting and immunohistochemical detection of relevant protein expression. RESULTS: and finally: 1) After the above screening, 81 active ingredients of PCW and 94 targets acting on diabetic ulcers were obtained. 2) 30 biological processes, 30 cellular compositions and 30 molecular functions were obtained by GO analysis; 28 signaling pathways were obtained by KEGG analysis. 3) The results of AO/EB staining assay, scratch assay and in vitro tube-forming assay showed that PCW has significant pro-vascular endothelial cell proliferation and pro-angiogenic effects in vitro. CONCLUSIONS: The results of this study confirmed the effect of the PCW in treating diabetic ulcers to a certain extent, and further revealed its mechanism of action in depth, which provides a new reference for the next step of Chinese medicine in treating diabetic ulcers.

Submarine groundwater discharge-driven nutrient fluxes in a typical mangrove and aquaculture bay of the Beibu Gulf, China.

To understand the role of submarine groundwater discharge (SGD) in a mangrove combined aquaculture ecosystem, groundwater samples and timeseries observations (27 h) of 224Ra, 223Ra, and nutrients were obtained during wet and dry seasons in Zhenzhu Bay, a typical mangrove and aquaculture ecosystem along the Beibu Gulf in China. The SGD rates in Zhenzhu Bay were estimated to be 22.3-44.5 cm/d in the wet season and 41.1-58.1 cm/d in the dry season, which were 0.8-1.6 and 9.8-14.1 times higher than the corresponding river water discharge values, respectively. Furthermore, SGD-driven dissolved inorganic nitrogen, dissolved inorganic orthophosphate, and dissolved inorganic silicate accounted for 72%, 56%, and 60% of the total nutrient input, respectively, during wet season, which increased to 93%, 98%, and 89% during dry season. The findings highlight that SGD plays an important role in the dissolved inorganic nutrient sources of Zhenzhu Bay, and that the effective utilization and management of the bay should consider SGD.