E-value: a superior alternative to P-value and its adjustments in DNA methylation studies.

DNA methylation plays a crucial role in transcriptional regulation. Reduced representation bisulfite sequencing (RRBS) is a technique of increasing use for analyzing genome-wide methylation profiles. Many computational tools such as Metilene, MethylKit, BiSeq and DMRfinder have been developed to use RRBS data for the detection of the differentially methylated regions (DMRs) potentially involved in epigenetic regulations of gene expression. For DMR detection tools, as for countless other medical applications, P-values and their adjustments are among the most standard reporting statistics used to assess the statistical significance of biological findings. However, P-values are coming under increasing criticism relating to their questionable accuracy and relatively high levels of false positive or negative indications. Here, we propose a method to calculate E-values, as likelihood ratios falling into the null hypothesis over the entire parameter space, for DMR detection in RRBS data. We also provide the R package 'metevalue' as a user-friendly interface to implement E-value calculations into various DMR detection tools. To evaluate the performance of E-values, we generated various RRBS benchmarking datasets using our simulator 'RRBSsim' with eight samples in each experimental group. Our comprehensive benchmarking analyses showed that using E-values not only significantly improved accuracy, area under ROC curve and power, over that of P-values or adjusted P-values, but also reduced false discovery rates and type I errors. In applications using real RRBS data of CRL rats and a clinical trial on low-salt diet, the use of E-values detected biologically more relevant DMRs and also improved the negative association between DNA methylation and gene expression.

Identification and validation of miR-29b-3p and LIN7A as important diagnostic markers for bone non-union by WGCNA.

Bone non-union is a common fracture complication that can severely impact patient outcomes, yet its mechanism is not fully understood. This study used differential analysis and weighted co-expression network analysis (WGCNA) to identify susceptibility modules and hub genes associated with fracture healing. Two datasets, GSE125289 and GSE213891, were downloaded from the GEO website, and differentially expressed miRNAs and genes were analysed and used to construct the WGCNA network. Gene ontology (GO) analysis of the differentially expressed genes showed enrichment in cytokine and inflammatory factor secretion, phagocytosis, and trans-Golgi network regulation pathways. Using bioinformatic site prediction and crossover gene search, miR-29b-3p was identified as a regulator of LIN7A expression that may negatively affect fracture healing. Potential miRNA-mRNA interactions in the bone non-union mechanism were explored, and miRNA-29-3p and LIN7A were identified as biomarkers of skeletal non-union. The expression of miRNA-29b-3p and LIN7A was verified in blood samples from patients with fracture non-union using qRT-PCR and ELISA. Overall, this study identified characteristic modules and key genes associated with fracture non-union and provided insight into its molecular mechanisms. Downregulated miRNA-29b-3p was found to downregulate LIN7A protein expression, which may affect the healing process after fracture in patients with bone non-union. These findings may serve as a prognostic biomarker and potential therapeutic target for bone non-union.

Associations between a normal-range free thyroxine concentration and ovarian reserve in infertile women undergoing treatment via assisted reproductive technology.

BACKGROUND: Some recent studies have shown that female subclinical hypothyroidism (SCH) is associated with diminished ovarian reserve (DOR). In this study, we aimed to investigate whether serum-free thyroxine (fT4) concentrations within the reference range are associated with ovarian reserve in women. METHODS: This cross-sectional study included 4933 infertile women with normal-range fT4 concentrations who received assisted reproductive technology treatment in our clinic. The data of women in different fT4 concentration tertiles (namely 12-15.33, 15.34-18.67, and 18.68-22 pmol/L) were compared with ovarian reserve markers, namely the anti-Müllerian hormone (AMH) concentration, the antral follicle count (AFC), and the number of aspirated oocytes. The primary outcomes were the AMH concentration and the risk of DOR, diagnosed as an AMH concentration < 1.1 ng/mL. RESULTS: The average ages of women in the low-normal, middle-normal, and high-normal fT4 tertiles were 33.20 (standard deviation [SD]: 5.11), 32.33 (SD: 5.13), and 31.61 (SD: 5.10) years, respectively (p < 0.0001). AMH concentrations (adjusted mean: 3.32 [95% confidence interval {CI}: 3.16 to 3.50] vs. 3.51 [3.40 to 3.62] vs. 3.64 [3.50 to 3.80] ng/mL, p = 0.022) were significantly different between the fT4 concentration tertiles. The risk of DOR was significantly increased in the low-normal (adjusted odds ratio: 1.61 [95% CI: 1.01 to 2.58]) and middle-normal (1.47 [95% CI: 1.00 to 2.16]) tertiles compared with the high-normal tertile. Subgroup analysis showed that AMH concentrations were significantly different among the fT4 concentration tertiles in women aged < 35 years (adjusted mean: 3.94 [95% CI: 3.70 to 4.20] vs. 4.25 [4.11 to 4.39] vs. 4.38 [4.18 to 4.58], p = 0.028), whereas this difference was not significant in women aged ≥ 35 years (p = 0.534). The general additive models using fT4 as a continuous variable indicated that a lower fT4 concentration within the normal range was significantly associated with a lower AMH concentration (p = 0.027), a lower AFC (p = 0.018), a lower number of aspirated oocytes (p = 0.001), and a higher risk of DOR (p = 0.007). CONCLUSION: Low-normal fT4 concentrations are associated with lower ovarian reserve in infertile women.

Reconstruction of recurrent shoulder dislocation with glenoid bone defect with 3D-printed titanium alloy pad: outcomes at 2-year minimum follow-up.

BACKGROUND: To evaluate the outcome of shoulder arthroscopy-assisted implantation of three-dimensional (3D)-printed titanium pads for recurrent shoulder dislocation with glenoid bone defects. METHODS: From June 2019 to May 2020, the clinical efficacy of 3D printed titanium pad implantation assisted by shoulder arthroscopy, for the treatment of recurrent shoulder dislocations with shoulder glenoid defects was retrospectively analyzed. The American Shoulder and Elbow Surgeons (ASES) shoulder, Rowe, and Constant scores were recorded before surgery and at 3 months, 6 months, 1 year, and 2 years after surgery. 3D computed tomography (CT) and magnetic resonance imaging were used to evaluate the location of the glenoid pad, bone ingrowth, joint degeneration, and osteochondral damage. RESULTS: The mean age of the 12 patients was 21.4 (19-24) years and the mean follow-up time was 27.6 (24-35) months. The Visual Analog Scale score significantly improved from 5.67 ± 1.98 preoperatively to 0.83 ± 0.58 postoperatively (p = 0.012). The postoperative ASES score was significantly increased to 87.91 ± 3.47 compared with preoperative ASES score (46.79 ± 6.45) (p < 0.01). Rowe and Constant scores also improved from 22.5 ± 12.34 and 56.58 ± 7.59 preoperatively to 90.83 ± 4.69 and 90.17 ± 1.89 at 2 years postoperatively, respectively. CT performed 2 years after surgery showed that the pad perfectly replenished the bone-defective part of the shoulder glenoid and restored the articular surface curvature of the shoulder glenoid in the anterior-posterior direction, and the bone around the central riser of the pad was tightly united. Magnetic resonance imaging 2 years after surgery showed that the humeral head osteochondral bone was intact, and there was no obvious osteochondral damage. CONCLUSIONS: 3D printed titanium pads are a reliable, safe, and effective surgical procedure for treating recurrent shoulder dislocations with glenoid bone defects.

rAAV-mediated over-expression of acid ceramidase prevents retinopathy in a mouse model of Farber lipogranulomatosis.

Farber disease (FD) is a rare monogenic lysosomal storage disorder caused by mutations in ASAH1 that results in a deficiency of acid ceramidase (ACDase) activity and the abnormal systemic accumulation of ceramide species, leading to multi-system organ failure involving neurological decline and retinopathy. Here we describe the effects of rAAV-mediated ASAH1 over-expression on the progression of retinopathy in a mouse model of FD (Asah1P361R/P361R) and its littermate controls (Asah1+/+ and Asah1+/P361R). Using a combination of non-invasive multimodal imaging, electrophysiology, post-mortem histology and mass spectrometry we demonstrate that ASAH1 over-expression significantly reduces central retinal thickening, ceramide accumulation, macrophage activation and limits fundus hyper-reflectivity and auto-fluorescence in FD mice, indicating rAAV-mediated over-expression of biologically active ACDase protein is able to rescue the anatomical retinal phenotype of Farber disease. Unexpectedly, ACDase over-expression in Asah1+/+ and Asah1+/P361R control eyes was observed to induce abnormal fundus hyper-reflectivity, auto-fluorescence and retinal thickening that closely resembles a FD phenotype. This study represents the first evidence of a gene therapy for Farber disease-related retinopathy. Importantly, the described gene therapy approach could be used to preserve vision in FD patients synergistically with broader enzyme replacement strategies aimed at preserving life.

Response characteristics of highland barley under freeze-thaw, drought and artemisinin stresses.

The freeze-thaw of early spring in China's Qinghai-Tibet Plateau is often accompanied by severe droughts. Artemisia annua, widely distributed in China, releases allelopathic substances, mainly artemisinin, to the environment and exerts a wide range of effects on crops. This paper studied the physiological effects of highland barley under freeze-thaw, drought, and artemisinin stress through indoor simulation experiments. The physiological response characteristics of superoxide dismutase (SOD) activity, catalase (POD) activity, net photosynthetic rate, relative water content (RWC), relative electrical conductivity, malondialdehyde (MDA) content, and soluble protein content in highland barley were analyzed. The results showed that artemisinin and drought contributed to the increase of SOD activity and the decrease of POD activity. Under the freeze-thaw stress, the SOD and POD activities both decreased firstly and then increased, but the effect of compound stress on POD was more complicated. Either artemisinin, drought, or low temperature could reduce the net photosynthetic rate of highland barley. Low temperature had more significant impacts on photosynthesis, and compound stress would show a single stress superimposed effect. Artemisinin, drought, and low temperature could reduce the RWC of highland barley, and increase the relative electrical conductivity and the concentration of soluble protein (except for low temperature stress above zero, which reduces the concentration of soluble protein). However, the effect of compound stress on soluble protein is more complex. The single stress of artemisinin and drought had no obvious effect on MDA content, while the MDA content was increased significantly under the freeze-thaw stress and the compound stress of artemisinin and drought, and the MDA content reached its peak at T1. The results are helpful to explore the effects of freeze-thaw, drought and artemisinin stress on the growth of highland barley under the background of the aridification of the Qinghai-Tibet Plateau, and provide ideas for rational agricultural management.

[Determination and comparison of 10 active components in different parts of Loropetalum chinensis based on ultra-high performance liquid chromatography-tandem mass spectrometry].

To establish a method for the simultaneous determination of ellagic acid, quercetin, gallic acid, kaempferol, myricetin, tiliroside, salidroside, isoquercetin, chlorogenic acid, and quinic acid in the leaves, flowers, fruits, and roots of Loropetalum chinensis by ultra-performance liquid chromatography-tandem mass spectrometry, and provide references for the development and utilization of L. chinensis resources. The analysis was performed on the chromatographic column ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 µm) with a gradient mobile phase of acetonitrile-0.2% formic solution at the flow rate of 0.3 mL·min~(-1). Column temperature was 30 ℃ and injection volume was 2 µL. Multiple reactive ion monitoring mode(MRM) was used in the negative ion ionization mode of electrospray ion source. The 10 active components had a good linear relationship, and the established method was stable, simple, and accurate. The 10 active components existed in different parts of L. chinensis, with significant different content. The main components in different parts of L. chinensis were polyphenols, with the highest content, followed by flavonoids. The content of 10 active components was generally high in flowers. Among them, the content of quinic acid was the highest, reaching 22.539 1 mg·g~(-1). This study elucidates the differences of active components in the same part and the different parts of L. chinensis, thereby providing basis for the research on the pharmacodynamic substances of L. chinensis and references for the comprehensive development and utilization of L. chinensis resources.

Hepatic Stellate Cells in Liver Fibrosis and siRNA-Based Therapy.

Hepatic fibrosis is a reversible wound-healing response to either acute or chronic liver injury caused by hepatitis B or C, alcohol, and toxic agents. Hepatic fibrosis is characterized by excessive accumulation and reduced degradation of extracellular matrix (ECM). Excessive accumulation of ECM alters the hepatic architecture leading to liver fibrosis and cirrhosis. Cirrhosis results in failure of common functions of the liver. Hepatic stellate cells (HSC) play a major role in the development of liver fibrosis as HSC are the main source of the excessive production of ECM in an injured liver. RNA interference (RNAi) is a recently discovered therapeutic tool that may provide a solution to manage multiple diseases including liver fibrosis through silencing of specific gene expression in diseased cells. However, gene silencing using small interfering RNA (siRNA) is encountering many challenges in the body after systemic administration. Efficient and stable siRNA delivery to the target cells is a key issue for the development of siRNA therapeutic. For that reason, various viral and non-viral carriers for liver-targeted siRNA delivery have been developed. This review will cover the current strategies for the treatment of liver fibrosis as well as discussing non-viral approaches such as cationic polymers and lipid-based nanoparticles for targeted delivery of siRNA to the liver.

Asymmetric Total Synthesis of Lancifodilactone G Acetate. 2. Final Phase and Completion of the Total Synthesis.

The asymmetric total synthesis of lancifodilactone G acetate was accomplished in 28 steps. The key steps in this synthesis include (i) an asymmetric Diels-Alder reaction for formation of the scaffold of the BC ring; (ii) an intramolecular ring-closing metathesis reaction for the formation of the trisubstituted cyclooctene using a Hoveyda-Grubbs II catalyst; (iii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; (iv) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G; and (v) a Dieckmann-type condensation reaction for installation of the A ring. The strategy and chemistry developed for the total synthesis will be useful in the synthesis of other natural products and complex molecules.

Effects of Moisture Content and Loading Profile on Changing Properties of Bone Micro-Biomechanical Characteristics.

BACKGROUND Our study explored the influences of hydration conditions and loading methods on the mechanical properties of cortical bones and cancellous bones. MATERIAL AND METHODS Elastic modulus and hardness of human cortical bones and cancellous bones that contained different moisture levels (20%, 30%, 40%, 50%, and 60%) were measured with nanoindentation with different peak loads and loading rates. Cortical bones with 20% and 60% moisture were tested with 30 nm, 40 nm, and 50 nm peak loads at 6 nm/s, 8 nm/s, and 10 nm/s loading rates, respectively. Cancellous bones with 5% or 40% moisture percentages were tested with 600 µN, 750 µN, and 1000 µN peak loads at 200 µN/s, 250 µN/s, and 333 µN/s loading rates, respectively. RESULTS Under the same loading condition, specimens with higher moisture contents showed decreased elastic modulus and hardness. Under different loading conditions, the loading modes had little influence on elastic modulus and hardness of cortical bone and cancellous bone with low moisture, but had significant influence on specimens with higher moistures. CONCLUSIONS The elastic modulus and bone hardness were affected by the moisture content and the loading conditions in cortical and cancellous bones with high hydration condition but not in those with low hydration condition.

The prevalence, awareness, treatment, and control of dyslipidemia in northeast China: a population-based cross-sectional survey.

BACKGROUND: Dyslipidemia is an important independent modifiable risk factor for cardiovascular disease. The aim of this study was to explore the current prevalence, awareness, treatment and control of dyslipidemia and its associated influence factors in northeast China. METHODS: In this population-based cross-sectional study, we adopted a multi-stage, stratified sampling method to obtain a representative sample of 4052 permanent residents aged 40 years and over from different urban and rural regions in Dehui City of Jilin Province. All subjects completed a questionnaire and were examined for risk factors. Continuous data were presented as means ± standard deviations (SD) and compared using the Student's t-test. Categorical variables were presented as proportions and compared using the Rao-Scott-χ 2 test in different subgroups. The associated influence factors for the prevalence, awareness, treatment and control of dyslipidemia were evaluated through multivariate logistic regression. RESULTS: The prevalence of dyslipidemia was 62.1% overall, with 33.5, 43.9, 0.6, and 8.8% for high total cholesterol, triglyceride, low-density lipoprotein cholesterol, and low high-density lipoprotein cholesterol, respectively. Among those with dyslipidemia, the proportion of subjects who were aware, treated, and controlled was 14.4, 33.9, and 19.9%, respectively. Overweight or obesity (OR = 2.156; 95% CI: 1.863, 2.533), hypertension (OR = 1.643; 95% CI: 1.425, 1.893), or diabetes mellitus (OR = 2.173; 95% CI: 1.661, 2.844) increased the prevalence of dyslipidemia, also these participants were more likely to be aware of their condition, however, this did not increase the likelihood of treatment and control. Living in urban areas and higher education level also increased the awareness of dyslipidemia. Personal history of coronary heart disease was the strongest influence factors associated with better awareness, treatment and control of dyslipidemia. Overweight or obesity (OR = 0.404; 95% CI: 0.235, 0.695) and lack of exercise (OR = 0.423; 95% CI: 0.215, 0.830) were associated with poor control of dyslipidemia. CONCLUSION: The prevalence of dyslipidemia among adults aged 40 years and over in northeast China was high, however, the awareness, treatment, and control of dyslipidemia was measured at far from desirable levels. Renewed efforts taking influence factors into account are needed to improve the current unsatisfactory condition.

Functionally defective germline variants of sialic acid acetylesterase in autoimmunity.

Sialic acid acetylesterase (SIAE) is an enzyme that negatively regulates B lymphocyte antigen receptor signalling and is required for the maintenance of immunological tolerance in mice. Heterozygous loss-of-function germline rare variants and a homozygous defective polymorphic variant of SIAE were identified in 24/923 subjects of European origin with relatively common autoimmune disorders and in 2/648 controls of European origin. All heterozygous loss-of-function SIAE mutations tested were capable of functioning in a dominant negative manner. A homozygous secretion-defective polymorphic variant of SIAE was catalytically active, lacked the ability to function in a dominant negative manner, and was seen in eight autoimmune subjects but in no control subjects. The odds ratio for inheriting defective SIAE alleles was 8.6 in all autoimmune subjects, 8.3 in subjects with rheumatoid arthritis, and 7.9 in subjects with type I diabetes. Functionally defective SIAE rare and polymorphic variants represent a strong genetic link to susceptibility in relatively common human autoimmune disorders.

A morphologic study of the transcallosal-interventricular foramen approach in endoscopic third ventriculostomy with magnetic resonance imaging.

There is a very wide range of applications in neurosurgery for the treatment of obstructive hydrocephalus by third ventriculostomy. To facilitate the operation, we measured the related data of transcallosal-interventricular foramen approach in endoscopic third ventriculostomy with the magnetic resonance images of the third ventricle from 103 healthy adults. We calculated the mean and standard deviation as well as the 95% confidence interval for the mean value of the measured data, which conformed to normal distribution. We used median and interquartile range to show its concentration and the level of variation when it does not.

Morphological study of surgical approach by superior temporal sulcus-temporal horn of lateral ventricle approach using volume rendering.

In this research, we acquired the length of the superior temporal sulcus, the shortest distance from the superior temporal sulcus to the temporal horn of the lateral ventricle, and the approach angle between the median sagittal plane and the shortest segment from the superior temporal sulcus to the temporal horn of the lateral ventricle measuring 98 specimens by magnetic resonance imaging volume rendering. At the same time, we preliminarily oriented the point of the superior temporal sulcus, which is closest to the temporal horn of the lateral ventricle, aimed at finding out the best entrance point of surgical approach through the superior temporal sulcus to the temporal horn of the lateral ventricle and reducing the damage to optic radiation as well as other nerve fibers during the operation. The results indicate that the point at the front side 3/5 of the superior temporal sulcus may be the ideal surgical approach entrance point, and there is no difference between 2 cerebral hemispheres (P < 0.05).

Biomechanical study of 3D-printed titanium alloy pad for repairing glenoid bone defect.

Background: The purpose of this study was to investigate the effect of 3D-printed technology to repair glenoid bone defect on shoulder joint stability. Methods: The shoulder joints of 25 male cadavers were tested. The 3D-printed glenoid pad was designed and fabricated. The specimens were divided into 5 groups. Group A: no bone defect and the structure of the glenoid labrum and joint capsule was intact; Group B: Anterior inferior bone defect of the shoulder glenoid; Group C: a pad with a width of 2 mm was installed; Group D: a pad with a width of 4 mm was installed; Group E: a pad with a width of 6 mm was installed. This study measured the distance the humeral head moved forward at the time of glenohumeral dislocation and the maximum load required to dislocate the shoulder. Results: The shoulder joint stability and humerus displacement was significantly lower in groups B and C compared with group A (p < .05). Compared with group A, the stability of the shoulder joint of group D was significantly improved (p < .05). However, there was no significant difference in humerus displacement between groups D and A (p > .05). In addition, compared with group A, shoulder joint stability was significantly increased and humerus displacement was significantly decreased in group E (p < .05). Conclusion: The 3D-printed technology can be used to make the shoulder glenoid pad to perfectly restore the geometric shape of the shoulder glenoid articular surface. Moreover, the 3D-printed pad is 2 mm larger than the normal glenoid width to restore the initial stability of the shoulder joint.

A simulation and risk assessment framework for water-energy-environment nexus: A case study in the city cluster along the middle reach of the Yangtze River, China.

In the Anthropocene, there is a strong interlinkage among water, energy, and the environment. The water-energy-environment nexus (WEEN) has been vigorously advocated as an emerging development paradigm and a global research agenda. Based on the nexus concept, a framework for the WEEN complex system simulation and risk assessment is developed. The three metropolitan areas of the city cluster along the middle reaches of the Yangtze River (CCMRYR) are taken as the objects. Regional policies are combined with generic shared socio-economic pathways (SSPs) to form a localized SSPs suitable for the research region. The dynamic simulation of the WEEN complex system and the risk analysis are carried out with the combination of system dynamics models and copula functions. Results show that: There are obvious differences in water utilization, energy consumption, air pollutant emissions, and water pollutant emissions among the three metropolitan areas. The issue of high carbon intensity in the Wuhan Metropolitan Coordinating Region needs to be emphasized and solved from the perspective of optimizing the industrial structure. Adhering to current development patterns, there will be successive peaks in water utilization, energy consumption, and carbon emissions in Wuhan, Dongting Lake, and Poyang Lake Metropolitan Coordinating Region by 2030, leading to high synergy risks at the systemic level, with maximum values of 0.84, 0.85, 0.62, respectively. A development path based on conservation priorities indicates that future policymaking needs to prioritize a resource-saving and pollution-control development pattern directed by technological upgrading against the backdrop of scarce natural resource endowments. The localized SSPs are a beneficial extension that enriches the narrative of regional-scale SSPs. The evolutionary trajectories and risk assessments of WEEN complex systems under different localized SSPs provide a sweeping insight into the consequences of policy decisions, thus enabling policymakers to appraise policy rationality and implement appropriate corrective measures.

Structure-based approaches for the design of 6-aryl-1-(3,4,5-trimethoxyphenyl)-1H-benzo[d][1,2,3]triazoles as tubulin polymerization inhibitors.

The colchicine binding site on tubulin has been widely acknowledged as an attractive target for anticancer drug exploitation. Here, we reported the structural optimization of the lead compound 4, which was proved in our previous work as a colchicine binding site inhibitor (CBSI). Based on docking researches for the active binding conformation of compound 4, a series of novel 6-aryl-1-(3,4,5-trimethoxyphenyl)-1H-benzo[d][1,2,3]triazole derivatives (9a-9x) were developed by replacing a CH group in the 1H-benzo[d]imidazole skeleton of compound 4 with a nitrogen atom as a hydrogen bond acceptor. Among them, compound 9a showed the strongest antiproliferative activity with IC50 values ranging from 14 to 45 nM against three human cancer cell lines (MCF-7, SGC-7901 and A549), lower than that of compound 4. Mechanistic studies indicated that compound 9a could inhibit tubulin polymerization, destroy the microtubule skeleton, block the cell cycle in G2/M phase, induce cancer cell apoptosis, prevent cancer cell migration and colony formation. Moreover, compound 9a significantly inhibited tumor growth in vivo without observable toxicity in the mice 4T1 xenograft tumor model. In conclusion, this report shows a successful case of the structure-based design approach of a potent tubulin polymerization inhibitor for cancer treatment.

Stereoselective Construction of the ABCDE Pentacyclic Motif of Phainanoids via Norrish-Yang Photocyclization Reaction.

A Norrish-Yang photocyclization reaction has been applied to regio- and stereoselective construction of the ABCDE pentacyclic motif of natural product phainanoids. The observed substrate conformation control implicates this powerful reaction could be applied to the construction of structurally diverse natural product scaffolds.

[Primary study of skin wound healing in rats for Loropetalum chinens].

OBJECTIVE: Cutaneous wound is a common health problem of humans. Loropetalum chinens, a medicinal plant, is widely used to treat wounds among the people. The research aims to observe whether L. chinens can promote the rats' wounds healing process, isolate the extracts primarily and commit the wound healing selection, which provide work basis for wound healing research of L. chinens. METHOD: First we analyzed the possible components with HC-MS/MS, then committed our wound healing experiments for L. chinens in the rat incision wound model and excision wound model, which are commonly used worldwide. After that, we carried on the preliminary isolation of the L. chinens and we screened the heal-promoting effects of the isolations in incision wound model. RESULT: L. chinens significantly accelerates the wound healing of rat's skin, shortens the healing period, enhances the healing intensity and promotes the cell proliferation and blood vessels formation around the wounds. The isolations, which are petroleum ether layer, ethyl acetate layer and n-butyl alcohol layer, exert heal-promoting effects. It indicates that the possible morphon that promotes wound healing may exist in these three components, with small polar. CONCLUSIONS: L. chinens possesses strong wound healing promoting effects, and the active constituent, with small polar, exists in petroleum ether layer, ethyl acetate layer and n-butyl alcohol layer, and we should focus on these three layers when carrying on further studies.

Modeling and forecasting CO2 emissions in China and its regions using a novel ARIMA-LSTM model.

Since China joined the WTO, its economy has experienced rapidly growth, resulting in significantly increase in fossil fuel consumption and corresponding rise in CO2 emissions. Currently, China is the world's largest emitter of CO2, the regional distribution is also extremely uneven. so, it is important to identify the factors influence CO2 emissions in the three regions and predict future trends based on these factors. This paper proposes 14 carbon emission factors and uses the random forest feature ranking algorithm to rank the importance of these factors in three regions. The main factors affecting CO2 emissions in each region are identified. Additionally, an ARIMA + LSTM carbon emission predict model based on the inverse error combination method is developed to address the linear and nonlinear relationships of carbon emission data. The findings suggest that the ARIMA + LSTM is more accurate in predicting the trend of CO2 emissions in China. Moreover, the ARIMA + LSTM is employed to forecast the future CO2 emission trends in China's east, central, and west regions, which can serve as a foundation for China's CO2 emission reduction initiatives.