Anatomical, chemical and endophytic fungal diversity of a Qi-Nan clone of Aquilaria sinensis (Lour.) Spreng with different induction times.

Recently, some new Qi-Nan clones of Aquilaria sinensis (Lour.) Spreng which intensively produces high-quality agarwood have been identified and propagated through grafting techniques. Previous studies have primarily focused on ordinary A. sinensis and the differences in composition when compared to Qi-Nan and ordinary A. sinensis. There are few studies on the formation mechanism of Qi-Nan agarwood and the dynamic changes in components and endophytic fungi during the induction process. In this paper, the characteristics, chemical composition, and changes in endophytic fungi of Qi-Nan agarwood induced after 1 year, 2 years, and 3 years were studied, and Qi-Nan white wood was used as the control. The results showed that the yield of Qi-Nan agarwood continued to increase with the induction time over a period of 3 years, while the content of alcohol extract from Qi-Nan agarwood reached its peak at two years. During the formation of agarwood, starch and soluble sugars in xylem rays and interxylary phloem are consumed and reduced. Most of the oily substances in agarwood were filled in xylem ray cells and interxylary phloem, and a small amount was filled in xylem vessels. The main components of Qi-Nan agarwood are also chromones and sesquiterpenes. With an increasing induction time, the content of sesquiterpenes increased, while the content of chromones decreased. The most abundant chromones in Qi-Nan agarwood were 2-(2-Phenethyl) chromone, 2-[2-(3-Methoxy-4-hydroxyphenyl) ethyl] chromone, and2-[2-(4-Methoxyphenyl) ethyl] chromone. Significant differences were observed in the species of the endophytic fungi found in Qi-Nan agarwood at different induction times. A total of 4 phyla, 73 orders, and 448 genera were found in Qi-Nan agarwood dominated by Ascomycota and Basidiomycota. Different induction times had a significant effect on the diversity of the endophytic fungal community in Qi-Nan. After the induction of agarwood formation, the diversity of Qi-Nan endophytic fungi decreased. Correlation analysis showed that there was a significant positive correlation between endophytic fungi and the yield, alcohol extract content, sesquiterpene content, and chromone content of Qi-Nan agarwood, which indicated that endophytic fungi play a role in promoting the formation of Qi-Nan agarwood. Qi-Nan agarwood produced at different induction times exhibited strong antioxidant capacity. DPPH free radical scavenging activity and reactive oxygen species clearance activity were significantly positively correlated with the content of sesquiterpenes and chromones in Qi-Nan agarwood.

[Efficacy analysis of OLIF combined with posterior percutaneous internal fixation in patients with lumbar spinal stenosis with or without redundant nerve roots].

OBJECTIVE: To investigate the clinical efficacy of oblique lumbar interbody fusion(OLIF) combined with posterior percutaneous internal fixation in patients with lumbar spinal stenosis with or without redundant nerve roots(RNRs). METHODS: A retrospective analysis of 92 patients with lumbar spinal stenosis treated by oblique lateral lumbar interbody fusion combined with posterior percutaneous internal fixation from June 2019 to June 2022 was performed. There were 32 males and 60 females, aged from 44 to 82 years old with an average of (63.67±9.93) years old. All patients were divided into RNRs positive group and RNRs negative group according to redundancy or not before operation. There were 38 patients in RNRs positive group, including 15 males and 23 females. The age ranged from 45 to 82 years old with an average of (65.45±10.37) years old. The disease duration was 24.00(12.00, 72.00) months. There were 54 patients in RNRs negative group, including 17 males and 37 females. The age ranged from 44 to 77 years old with an average of (62.42±9.51) years old. The disease duration was 13.50(9.00, 36.00) months. The general data of patients were recorded, including operation time, intraoperative blood loss and complications. The imaging parameters before and after operation were observed, including the number of stenosis segments, intervertebral space height, lumbar lordosis angle and dural sac area. The visual analogue scale (VAS) was used to evaluate the back and lower extremity pain, and the Oswestry disability index (ODI) was used to evaluate the activities of daily living. RESULTS: All patients were followed up for 8 to 18 months with an average of (11.04±3.61) months, and no complications were found during the follow-up period.The number of stenosis segments in RNRs positive group (1.71±0.46) was more than that in RNRs negative group(1.17±0.38). In RNRs positive group, intervertebral space height, dural sac area, low back pain VAS, lower extremity pain VAS, ODI score were (1.11±0.19) cm, (0.46±0.17) cm2, (5.39±1.00) scores, (5.05±1.01) points, (55.74±4.05) points, respectively. RNRs negative groups respectively (0.97±0.23) cm, (0.69±0.26) cm2, (4.50±0.77) scores, (4.00±0.58) scores, (47.33±3.43) %. In RNRs positive group, intervertebral space height, dural sac area, low back pain VAS, leg pain VAS, ODI score were (1.60±0.19) cm, (0.74±0.36) cm2, (3.39±0.72) scores, (3.05±1.01) scores, (46.74±4.82) scores, respectively. RNRs negative groups respectively (1.48±0.25) cm, (1.12±0.35) cm2, (3.00±0.82) scores, (3.00±0.82) scores, (37.67±3.58) %. The postoperative intervertebral space height, dural sac area, low back pain VAS score, lower extremity pain VAS and ODI score of the patients in the RNRs positive group and the negative group were significantly improved compared with those before operation, and the differences were statistically significant (P<0.05). There were statistically significant differences in the number of stenosed segments, preoperative intervertebral space height, dural sac area, low back pain VAS, lower extremity pain VAS, and ODI between the two groups(P<0.05). There were significant differences in postoperative intervertebral space height and postoperative ODI between the two groups(P<0.05), but there was no significant difference in intervertebral space height before and after operation and ODI score before and after operation(P>0.05). There were significant differences in operation time, intraoperative blood loss, postoperative dural sac area, difference of dural sac area before and after operation, postoperative low back pain VAS, difference of low back pain VAS score before and after operation, difference of lower extremity pain VAS before and after operation between the two groups(P<0.05). CONCLUSION: OLIF combined with posterior percutaneous internal fixation has a good effect on patients with or without RNRs. Multi-segmental lumbar spinal stenosis and decreased dural sac area may lead to the occurrence of RNRs, and LSS patients with RNRs have more severe symptoms. LSS patients with RNRs have worse surgical outcomes than those without RNRs.

Machine learning in risk prediction of continuous renal replacement therapy after coronary artery bypass grafting surgery in patients.

OBJECTIVES: This study aimed to develop machine learning models for risk prediction of continuous renal replacement therapy (CRRT) following coronary artery bypass grafting (CABG) surgery in intensive care unit (ICU) patients. METHODS: We extracted CABG patients from the electronic medical record system of the hospital. The endpoint of this study was the requirement for CRRT after CABG surgery. The Boruta method was used for feature selection. Seven machine learning algorithms were developed to train models and validated using 10 fold cross-validation (CV). Model discrimination and calibration were estimated using the area under the receiver operating characteristic curve (AUC) and calibration plot, respectively. We used the SHapley Additive exPlanations (SHAP) method to illustrate the effects of the features attributed to the model and analyze the effects of individual features on the output of the mode. RESULTS: In this study, 72 (37.89%) patients underwent CRRT, with a higher mortality compared to those patients without CRRT. The Gaussian Naïve Bayes (GNB) model with the highest AUC were considered as the final predictive model and performed best in predicting postoperative CRRT. The analysis of importance revealed that cardiac troponin T, creatine kinase isoenzyme, albumin, low-density lipoprotein cholesterol, NYHA, serum creatinine, and age were the top seven features of the GNB model. The SHAP force analysis illustrated how created model visualized individualized prediction of CRRT. CONCLUSIONS: Machine learning models were developed to predict CRRT. This contributes to the identification of risk variables for CRRT following CABG surgery in ICU patients and enables the optimization of perioperative managements for patients.

Salty treatment increased bioactive compounds accumulation during agarwood development in Aquilaria sinensis trees.

To compare the bioactive compounds in agarwood induced by different methods in Aquilaria sinensis(Lour.) Gilg trees, a two dimensional thin layer chromatograph(2D-TLC) combined with effect directive analysis(EDA) was developed. Three antioxidants were found by 2D-TLC-DPPH and further identified as 2-(2-phenylethyl) chromones(PECs) with LC-MS/MS. The 3 antioxidants decreased along agarwood formation and their compositions in drilling induced agarwood differed with those in microbe culture induced agarwood. Further study showed NaCl treatment promoted antioxidants accumulation in agarwood induced by drilling or hot drilling. Hot drilling combined with salty stimulation was most efficient in some chemicals accumulation, which were identified as PECs with antioxidant, tyrosinase or ß-glucosidase inhibiting activities by 2D-TLC-EDA-LC-MS/MS. This study provided a 2D-TLC-EDA-LC-MS/MS method for bioactive compounds screen and qualification of agarwood. Based on this method, non-conventional methods were found to accelerate the accumulation of some bioactive PECs in A. sinensis trees.

Identification and characterization of two O-methyltransferases involved in methylated 2-(2-phenethyl) chromones biosynthesis in agarwood.

The 2-(2-phenethyl)chromones (PECs) are the signature constituents responsible for the fragrance and pharmacological properties of agarwood. O-methyltransferases (OMTs) are necessary for the methylated PECs biosynthesis, however, there is little information known about OMTs in Aquilaria sinensis. In this study, we identified 29 OMT genes from the A. sinensis genome. Expression analysis showed they were differentially expressed in different tissues and responded to drill wounding. Comprehensive analysis of the gene expression and methylated PECs content revealed that the AsOMT2, AsOMT8, AsOMT11, AsOMT16, and AsOMT28 could potentially be involved in methylated PECs biosynthesis. The vitro enzyme assays and functional analysis in Nicotiana benthamiana demonstrated that AsOMT11 and AsOMT16 could methylate 6-hydroxy-2-(2-phenylethyl)chromone to form 6-methoxy-2-(2-phenylethyl) chromone. The transient overexpression experiment in Qi-Nan revealed that AsOMT11 and AsOMT16 could significantly promote the accumulation of three major methylated PECs. Our results provide candidate genes for the mass production of methylated PECs using synthetic biology.

PDGFBB facilitates tumorigenesis and malignancy of lung adenocarcinoma associated with PI3K-AKT/MAPK signaling.

Lung adenocarcinoma (LUAD) remains one of the most aggressive tumors and the efficacy of conventional treatment has been bleak. Nowadays, gene-targeted therapy has become a new favorite in tumor therapy. Herein, we investigated the effect of platelet derived growth factor BB (PDGFBB) on LUAD. Firstly, PDGFBB was upregulated in LUAD patients and closely linked with poor survival. Furthermore, the expression of PDGFBB and PDGFRα/ß in LUAD cells was higher than that in normal lung cells. By loss-of-function with herpes simplex virus (HSV)-PDGFi-shRNA, we found that PDGFBB knockdown caused a significant decrease in proliferation and migration, but evoked apoptosis of LUAD cells in vitro. Conversely, exogenous PDGFBB held adverse effect. Additionally, A549 cells with PDGFBB knockdown had a low probability of tumorigenesis in vivo. Moreover, PDGFBB knockdown restrained the growth of xenografts derived from normal A549 cells. Mechanistically, PDGFBB knockdown suppressed PI3K/AKT and Ras/MAPK signaling, while PDGFBB was the opposite. Therefore, we concluded that PDGFBB might facilitate the tumorigenesis and malignancy of LUAD through its functional downstream nodes-PI3K/AKT and Ras/MAPK signaling, which supported that PDGFBB could serve as a rational therapeutic target for LUAD.

Tanshinone IIA attenuates osteoarthritis via inhibiting aberrant angiogenesis in subchondral bone.

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.

Age-related decline in melatonin contributes to enhanced osteoclastogenesis via disruption of redox homeostasis.

BACKGROUND: Increased oxidative stress contributes to enhanced osteoclastogenesis and age-related bone loss. Melatonin (MT) is an endogenous antioxidant and declines with aging. However, it was unclear whether the decline of MT was involved in the enhanced osteoclastogenesis during the aging process. METHODS: The plasma level of MT, oxidative stress status, bone mass, the number of bone marrow-derived monocytes (BMMs) and its osteoclastogenesis were analyzed in young (3-month old) and old (18-month old) mice (n = 6 per group). In vitro, BMMs isolated from aged mice were treated with or without MT, followed by detecting the change of osteoclastogenesis and intracellular reactive oxygen species (ROS) level. Furthermore, old mice were treated with MT for 2 months to investigate the therapeutic effect. RESULTS: The plasma level of MT was markedly lower in aged mice compared with young mice. Age-related decline in MT was accompanied by enhanced oxidative stress, osteoclastogenic potential and bone loss. MT intervention significantly suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, decreased intracellular ROS and enhanced antioxidant capacity of BMMs from aged mice. MT supplementation significantly attenuated oxidative stress, osteoclastogenesis, bone loss and deterioration of bone microstructure in aged mice. CONCLUSIONS: These results suggest that age-related decline of MT enhanced osteoclastogenesis via disruption of redox homeostasis. MT may serve as a key regulator in osteoclastogenesis and bone homeostasis, thereby highlighting its potential as a preventive agent for age-related bone loss.

Factors Associated with Re-Displacement after Nonsurgical Treatment of Distal Radius Fractures in Adults: A Retrospective Study.

OBJECTIVE: Closed reduction combined with external fixation is a frequently utilized approach for treating distal radial fractures in adults. Nonetheless, the potential for re-displacement following external fixation remains. Analyzing the factors influencing re-displacement after nonsurgical treatment of distal radial fractures in adults is vital for preventing re-displacement and making prognostic assessments. METHODS: A retrospective analysis was performed on 884 patients who underwent nonsurgical treatment for distal radius fractures in the reduction room of the Orthopedics and Traumatology Department of Integrated Traditional Chinese and Western Medicine at Tianjin Hospital, Tianjin, China, between July 2019 and December 2022. Patients were categorized into two groups, namely displaced and nondisplaced, based on radiographic outcomes. Factors affecting fracture re-displacement were examined, including sex, age, side, AO/OTA type, external fixation, and radiographic outcomes at pre-reduction and immediate reduction. Logistic regression analysis was employed to identify the risk factors for fracture re-displacement, and ROC curves were constructed. RESULTS: Among the 884 patients, 563 (63.69%) experienced re-displacement after fracture reduction. There were no statistically significant differences (p > 0.05) between the two groups in terms of gender, external fixation method, and palmar tilt angle at pre-reduction and immediate reduction, while significant differences (p < 0.05) were observed in age, side, AO/OTA type, and radial inclination, radial length, and radiographic outcomes of ulnar variance at pre-reduction and immediate reduction. Multifactorial logistic regression analysis revealed that age (odds ratio [OR] = 1.027, p < 0.001), AO/OTA type (OR = 2.327, p = 0.005), ulnar variance at pre-reduction (OR = 1.142, p = 0.048), and ulnar variance at immediate reduction (OR = 1.685, p < 0.001) were significant factors (p < 0.05) associated with re-displacement following nonoperative treatment of adult distal radius fractures. For patients aged ≥60 years, the amount of missing radiographic outcomes was positively correlated with age. The receiver operating characteristic curve demonstrated that age ≥65.5 years, ulnar variance >3.26 mm at pre-reduction, and ulnar variance >2.055 mm at immediate reduction were high-risk factors for fracture re-displacement. CONCLUSIONS: Nonsurgical treatment of distal radius fractures exhibits a higher rate of re-displacement. Age, AO/OTA type, pre-reduction, and immediate reduction ulnar variance are key factors predicting fracture re-displacement.

Mendelian randomization analysis reveals the impact of physical and occupational activities on the risk of gastroesophageal reflux disease and Barrett's esophagus.

BACKGROUND: Recent studies have indicated that participating in physical activity may provide a safeguard against gastroesophageal reflux disease (GERD). Nevertheless, the precise links between physical and occupational activity and the occurrence of GERD and Barrett's esophagus (BE) are still uncertain. METHODS: Conducting univariate and multivariate Mendelian randomization investigations to examine the causal relationship between exposures and outcomes. Genetic variation simulation was used in randomized experiments. Data on physical and occupational activity were obtained from the UK Biobank and GWAS catalog. In the meantime, data on GERD and BE were extracted from a high quality meta-analysis. RESULTS: The results of univariate Mendelian randomization analysis using multiple methods suggest a causal relationship between strenuous sports or other forms of exercise (as a protective factor) and GERD/BE. At the same time, three types of occupational related physical activities, including heavy manual or physical work, shift work and walking or standing work, are risk factors for GERD/BE and have a causal relationship with them. These results were reconfirmed through multivariate Mendelian randomization analysis, which excluding the influence of other potential confounding factors. CONCLUSIONS: The findings indicated that strenuous sports or other forms of exercise could lower the likelihood of GERD/BE, while excessive physical strain in the workplace, prolonged periods of standing or walking, and shift work could raise the risk of GERD/BE. Acknowledging this risk and implementing suitable measures can contribute to the prevention of GERD and BE, thus mitigating the associated health burden.

Synthesis and antitumor activity evaluation of coumarin Mannich base derivatives.

Twenty-one new coumarin Mannich base derivatives (11a-u) were synthesized, which exhibited antiproliferation activities in HepG2 (liver cancer), A549 (lung cancer), MCF-7 (breast cancer), and HT-29 (colon cancer). Most of the target compounds showed the most potent activity against HepG2 cells compared with other cancer cells, compound 11g showed the strongest antiproliferative activity (2.10 µM) against HepG2, even superior to the positive control drug 5-FU(5.49 µM). The nitric oxide (NO) release of all compounds in HepG2 cells was determined, of which compound 11g showed high levels of NO release (10.8 µM). Notably, the solubility of compound 11g increased 13-fold compared with the lead 8. The preliminary cytotoxicity studies suggest that 11g had little effect on LO2 cells(normal liver cells, >50 µM). The effect of compound 11g on the apoptosis of HepG2 cells was also studied, and the results showed that the induction effect of compound 11g on apoptosis is a concentration-dependent manner. Our results indicate that compound 11g might be a promising lead for further studies.

Comprehensive quality evaluation of Guge fengtong tablets / 中国药房

OBJECTIVE To establish a method for the content determination of 11 components such as protodioscin in Guge fengtong tablets， and to evaluate the comprehensive quality of Guge fengtong tablets by combining with chemometric analysis and entropy weight-technique for order preference by similarity to ideal solution （EW-TOPSIS） method. METHODS HPLC method was adopted. The determination was performed on Agilent Eclipse Plus C18 column with a mobile phase consisted of acetonitrile- 0.2% phosphoric acid solution at the flow rate of 1.0 mL/min by gradient elution. The column temperature was set at 30 ℃ . The detection wavelengths were set at 203 nm （0-28 min， protodioscin， methyl protodioscin， pseudoprotodioscin， dioscin） and 280 nm （28-60 min， catechin， epicatechin， liquiritigenin， medicarpin， 6-gingerol， 8-gingerol， 10-gingerol）； the sample size was 10 μL. Using epicatechin as the internal reference， quantitative analysis of multi-components by single marker （QAMS） method was used to determine the contents of protodioscin， methyl protodioscin， pseudoprotodioscin， dioscin， catechin， liquiritigenin， medicarpin， 6-gingerol， 8-gingerol and 10-gingerol， which were compared with the results of the external standard method. SPSS 26.0 software and SIMCA 14.1 software were used for principal component analysis and orthogonal partial least squares-discriminant analysis， with variable importance in projection （VIP） value greater than 1 as the standard， to screen for differential markers that affect the quality； the EW-TOPSIS method was adopted to evaluate the quality of 15 batches of samples comprehensively.RESULTS The contents of protodioscin， methyl protodioscin， pseudoprotodioscin， dioscin， catechin， liquiritigenin， medi-carpin， 6-gingerol， 8-gingerol and 10-gingerol determined by HPLC combined with QAMS were 6.330-10.863， 1.150-2.274， 0.431- 0.740， 2.818-4.823， 0.826-1.510， 0.043-0.094， 0.079-0.231， 0.479-1.020， 0.146-0.288， 0.118-0.318 mg/g， respectively； there were no statistical significances， compared with the external standard method （P＞0.05）. A total of 15 batches of samples were clustered into 3 groups， with S1-S6， S7-S10， and S11-S15 clustered into one group， respectively. The VIP values of protodioscin， epicatechin， dioscin and 6-gingerol were greater than 1. Euclidean closeness values of the optimal solution （C）i for 15 batches of samples were 0.163 5 to 0.703 7， and Ci values of S11-S15 were all higher than 0.6. CONCLUSIONS The established QAMS method is accurate and simple， and can be used for comprehensive quality evaluation of Guge fengtong tablets， by combining with chemometric analysis and EW-TOPSIS method. Protodioscin， epicatechin， dioscin and 6-gingerol are the differential markers that affect the quality of Guge fengtong tablets. Samples S11-S15 have better quality.

Toward Linear Scaling Auxiliary-Field Quantum Monte Carlo with Local Natural Orbitals.

We develop a local correlation variant of auxiliary-field quantum Monte Carlo (AFQMC) based on local natural orbitals (LNO-AFQMC). In LNO-AFQMC, independent AFQMC calculations are performed for each localized occupied orbital using a truncated set of tailored orbitals. Because the size of this space does not grow with the system size for a target accuracy, the method has linear scaling. Applying LNO-AFQMC to molecular problems containing a few hundred to a thousand orbitals, we demonstrate convergence of total energies with significantly reduced costs. The savings are more significant for larger systems and larger basis sets. However, even for our smallest system studied, we find that LNO-AFQMC is cheaper than canonical AFQMC, in contrast with many other reduced-scaling methods. Perhaps most significantly, we show that energy differences converge much more quickly than total energies, making the method ideal for applications in chemistry and material science. Our work paves the way for linear scaling AFQMC calculations of strongly correlated systems, which would have a transformative effect on ab initio quantum chemistry.

Drebrin Protects Assembled Actin from INF2-FFC-mediated Severing and Stabilizes Cell Protrusions.

Highly specialized cells, such as neurons and podocytes, have arborized morphologies that serve their specific functions. Actin cytoskeleton and its associated proteins are responsible for the distinctive shapes of cells. The mechanism of their cytoskeleton regulation - contributing to cell shape maintenance - is yet to be fully clarified. Inverted formin 2 (INF2), one of the modulators of the cytoskeleton, is an atypical formin that can both polymerize and depolymerize actin filaments depending on its molar ratio to actin. Prior work has established that INF2 binds to the sides of actin filaments and severs them. Drebrin is another actin-binding protein that also binds filaments laterally and stabilizes them, but the interplay between drebrin and INF2 on actin filament stabilization is not well understood. Here, we have used biochemical assays, electron microscopy, and total internal reflection fluorescence microscopy imaging to show that drebrin protects actin filaments from severing by INF2 without inhibiting its polymerization activity. Notably, truncated drebrin - DrbA1-300 - is sufficient for this protection, though not as effective as the full-length protein. INF2 and drebrin are abundantly expressed in highly specialized cells and are crucial for the temporal regulation of their actin cytoskeleton, consistent with their involvement in peripheral neuropathy.

[In vitro biological evaluation of PEGylated poly(glycerol sebacate)/ß-TCP-coating modified magnesium alloy].

PURPOSE: To prepare PEGS/ß-TCP modified magnesium alloy (PEGS/ß-TCP/MZG) membranes by forming a glycolated poly(sebacate)/ß-tricalcium phosphate (PEGS/ß-TCP) coating on the surface of magnesium-zinc-gadolinium alloy (MZG) membranes, and to evaluate the osteogenic induction activity and immunomodulatory properties of PEGS/ß-TCP/MZG using the material extract medium. METHODS: PEGS/ß-TCP coating was prepared on the surface of MZG by solvent method, and the PEGS/ß-TCP/MZG membrane was fabricated and compared with PEGS/ß-TCP and MZG to examine the morphology, composition, and hydrophilicity. The amount of magnesium ions released and the pH value of the materials were tested after 3 days of immersion. The cell viability and osteogenic differentiation of MC3T3 cells induced by extract medium were investigated by CCK-8 assay, ALP and mineralized nodule staining. The cell viability and polarization of RAW cells induced by extract medium were then investigated. The expression of macrophage-secreted cytokines was examined by PCR analysis. GraphPad Prism 9.0 software package was used for statistical analysis. RESULTS: PEGS/ß-TCP/MZG membranes with PEGS/ß-TCP coating tightly embedded with MZG were successfully fabricated, and the material had good hydrophilicity. The results of degradation experiments indicated that the PEGS/ß-TCP coating effectively slowed down the degradation rate of MZG, leading to a lower pH value and concentration of Mg2+ ion in the extract medium of PEGS/ß-TCP/MZG group. The results of in vitro cell experiments showed that PEGS/ß-TCP/MZG had no significant effect on the proliferation activity of both MC3T3-E1 and macrophages. PEGS/ß-TCP/MZG significantly enhanced the expression of ALP and mineralized nodule staining in MC3T3-E1. Although there was no significant difference in macrophage polarization pattern between PEGS/ß-TCP and PEGS/ß-TCP/MZG groups, PEGS/ß-TCP/MZG further reduced inflammation based on the immunomodulation of PEGS/ß-TCP coating related TNF-α expression and increased osteogenesis related TGF-ß expression. CONCLUSIONS: MZG membrane modified by PEGS/ß-TCP may provide a new material option for the development of bone tissue engineering.

Can Spin-Component Scaled MP2 Achieve kJ/mol Accuracy for Cohesive Energies of Molecular Crystals?

Attaining kJ/mol accuracy in cohesive energy for molecular crystals is a persistent challenge in computational materials science. In this study, we evaluate second-order Møller-Plesset perturbation theory (MP2) and its spin-component scaled models for calculating cohesive energies for 23 molecular crystals (X23 data set). Using periodic boundary conditions and Brillouin zone sampling, we converge results to the thermodynamic and complete basis set limits, achieving an accuracy of about 2 kJ/mol (0.5 kcal/mol), which is rarely achieved in previous MP2 calculations for molecular crystals. When compared to experimental data, our results have a mean absolute error of 12.9 kJ/mol, comparable to Density Functional Theory with the PBE functional and TS dispersion correction. By separately scaling the opposite-spin and same-spin correlation energy components, using predetermined parameters, we reduce the mean absolute error to 9.5 kJ/mol. Further fine-tuning of these scaling parameters specifically for the X23 data set brings the mean absolute error down to 7.5 kJ/mol.

Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial.

BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

Deep learning-based lung sound analysis for intelligent stethoscope.

Auscultation is crucial for the diagnosis of respiratory system diseases. However, traditional stethoscopes have inherent limitations, such as inter-listener variability and subjectivity, and they cannot record respiratory sounds for offline/retrospective diagnosis or remote prescriptions in telemedicine. The emergence of digital stethoscopes has overcome these limitations by allowing physicians to store and share respiratory sounds for consultation and education. On this basis, machine learning, particularly deep learning, enables the fully-automatic analysis of lung sounds that may pave the way for intelligent stethoscopes. This review thus aims to provide a comprehensive overview of deep learning algorithms used for lung sound analysis to emphasize the significance of artificial intelligence (AI) in this field. We focus on each component of deep learning-based lung sound analysis systems, including the task categories, public datasets, denoising methods, and, most importantly, existing deep learning methods, i.e., the state-of-the-art approaches to convert lung sounds into two-dimensional (2D) spectrograms and use convolutional neural networks for the end-to-end recognition of respiratory diseases or abnormal lung sounds. Additionally, this review highlights current challenges in this field, including the variety of devices, noise sensitivity, and poor interpretability of deep models. To address the poor reproducibility and variety of deep learning in this field, this review also provides a scalable and flexible open-source framework that aims to standardize the algorithmic workflow and provide a solid basis for replication and future extension: https://github.com/contactless-healthcare/Deep-Learning-for-Lung-Sound-Analysis .

[Clinical significance and risk factors of redundant nerve root in patients with lumbar spinal stenosis].

OBJECTIVE: To investigate the clinical significance and screen the risk factors of redundant nerve roots(RNRs) in patients with lumbar spinal stenosis. METHODS: The clinical data of 196 patients with lumbar spinal stenosis in the department of Spinal Surgery, Yijishan Hospital, Wannan Medical College from April 1, 2015 to November 30, 2020 were retrospectively analyzed. All patients were divided into RNRs positive group and RNRs negative group according to the presence of RNRs. The differences in general clinical data, imaging parameters, visual analogue scale(VAS), Oswestry disability index(ODI), and other indicators between the two groups were compared. The risk factors which are highly correlated with RNRs were screened by binary Logistic regression analysis. RESULTS: There were 59 cases in the RNRs positive group, with an occurrence rate of 29.95% (59/137), and 137 cases in the RNRs negative group. The incidence rate of RNRs in 196 patients with lumbar spinal stenosis was 30.10% (59/196). VAS and ODI scores of patients in the two groups were statistically significant (P<0.05), and clinical symptoms of patients in the RNRs positive group were more severe than those in the RNRs negative group. There were significant differences in age, number of stenosis segments, average area of lumbar dural sac, area of the narrowest segment and the narrowest segment(P<0.05). Binary logistic regression analysis showed that the number of stenosis segments, the average median sagittal diameter of spinal canal, and the average area of dural sac in lumbar intervertebral space were correlated with the generation of RNRs (P<0.05). The regression coefficient of the number of stenosis segments was -1.115, the regression coefficient of the median sagittal diameter of the spinal canal was -1.707, and the regression coefficient of the mean dural sac area of the lumbar intervertebral space was 7.556. CONCLUSION: The clinical symptoms of patients with lumbar spinal stenosis accompanied by RNRs are more severe than those without them. The number of narrow segments, median sagittal diameter of the spinal canal, and the area of the lumbar intervertebral dural sac are the high-risk factors for RNRs, with the area of the lumbar intervertebral dural sac has the highest correlation.

Structural Characterization and Anticomplement Activity of an Acidic Heteropolysaccharide from Lysimachia christinae Hance.

A novel acidic heteropolysaccharide (LCP-90-1) was isolated and purified from a traditional "heat-clearing" Chinese medicine, Lysimachia christinae Hance. LCP-90-1 (Mw, 20.65 kDa) was composed of Man, Rha, GlcA, Glc, Gal, and Ara, with relative molar ratios of 1.00: 3.00: 11.62: 1.31: 1.64: 5.24. The backbone consisted of 1,4-α-D-GlcpA, 1,4-α-D-Glcp, 1,4-ß-L-Rhap, and 1,3,5-α-L-Araf, with three branches of ß-D-Galp-(1 → 4)-ß-L-Rhap-(1→, α-L-Araf-(1→ and α-D-Manp-(1→ attached to the C-5 position of 1,3,5-α-L-Araf. LCP-90-1 exhibited potent anticomplement activity (CH50: 135.01 ± 0.68 µg/mL) in vitro, which was significantly enhanced with increased glucuronic acid (GlcA) content in its degradation production (LCP-90-1-A, CH50: 28.26 ± 0.39 µg/mL). However, both LCP-90-1 and LCP90-1-A were inactivated after reduction or complete acid hydrolysis. These observations indicated the important role of GlcA in LCP-90-1 and associated derivatives with respect to anticomplement activity. Similarly, compared with LCP-90-1, the antioxidant activity of LCP-90-1-A was also enhanced. Thus, polysaccharides with a high content of GlcA might be important and effective substances of L. christinae.