Maternal pregnancy diet quality, night eating, and offspring metabolic health: the GUSTO study.

BACKGROUND: We investigated the understudied influence of maternal diet quality, food timing, and their interactions during pregnancy on offspring metabolic health. METHODS: Maternal diet at 26-28 weeks' gestation was assessed using a 24-h recall and adherence to the modified-healthy-eating-index (HEI-SGP) reflects diet quality. Predominant night-eating (PNE) was defined as consuming >50% of total daily energy intake from 19:00 to 06:59. Outcomes were offspring composite metabolic syndrome score and its components measured at age 6 years. Multivariable linear regressions adjusted for relevant maternal and child covariates assessed associations of diet quality and PNE with these outcomes. RESULTS: Up to 758 mother-child pairs were included. The mean(SD) maternal HEI-SGP score was 52.3(13.7) points (theoretical range: 0-100) and 15% of the mothers demonstrated PNE. Maternal diet quality showed inverse relationship with offspring Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [ß(95% CI): -0.08(-0.15, -0.02) per-10-point HEI-SGP increment; P = 0.012]. Maternal PNE was associated with a higher offspring HOMA-IR [0.28(0.06, 0.50); P = 0.012], with similar estimates after adjustment for children's BMI and diet quality; the association was stronger for boys (P-interaction<0.001) and among mothers with lower diet quality (

Higher early pregnancy plasma myo-inositol associates with increased postprandial glycaemia later in pregnancy: Secondary analyses of the NiPPeR randomized controlled trial.

AIM: Myo-inositol supplementation from ~13 weeks' gestation reportedly improves glycaemia regulation in metabolically at-risk women, with speculation that earlier supplementation might bring further improvement. However, the NiPPeR trial of a myo-inositol-containing supplement starting preconception did not lower gestational glycaemia in generally healthy women. We postulated that the earlier timing of supplementation influences the maternal metabolic adaptation for gestational glycaemia regulation. METHODS: In total, 585 women were recruited from Singapore, UK and New Zealand for the NiPPeR study. We examined associations of plasma myo-inositol concentrations at 7 and 28 weeks' gestation with 28 weeks plasma glucose (PG; fasting, and 1 h and 2 h in 75 g oral glucose tolerance test) and insulin indices using linear regression adjusting for covariates. RESULTS: Higher 7-week myo-inositol, but not 28-week myo-inositol, associated with higher 1 h PG [ßadj (95% confidence intervals) 0.05 (0.01, 0.09) loge mmol/L per loge µmol/L, p = .022] and 2 h PG [0.08 (0.03, 0.12), p = .001]; equivalent to 0.39 mmol/L increase in 2 h PG for an average 7-week myo-inositol increase of 23.4 µmol/L with myo-inositol supplementation. Higher 7-week myo-inositol associated with a lower 28-week Stumvoll index (first phase), an approximation of insulin secretion [-0.08 (-0.15, -0.01), p = .020] but not with 28-week Matsuda insulin sensitivity index. However, the clinical significance of a 7-week myo-inositol-related increase in glycaemia was limited as there was no association with gestational diabetes risk, birthweight and cord C-peptide levels. In-silico modelling found higher 28-week myo-inositol was associated with lower gestational glycaemia in White, but not Asian, women after controlling for 7-week myo-inositol effects. CONCLUSION: To our knowledge, our study provides the first evidence that increasing first trimester plasma myo-inositol may slightly exacerbate later pregnancy post-challenge glycaemia, indicating that the optimal timing for starting prenatal myo-inositol supplementation needs further investigation.

One-pot tandem reduction and site-selective halogenation of nitroarenes.

Halogenated aryl amines are a widely used chemical feedstock in the pharmaceutical and agrochemical industries. Achieving a single regioselective product from the para-selective halogenation of the aryl ring is significantly challenging because of the presence of several C-H bonds with similar reactivities. In this study, single para-halogenated aniline derivatives were prepared by the cascade para-selective halogenation (Cl, Br) and reduction of nitrobenzene derivatives using a mixture of SnCl2/SnCl4 salts. The mechanistic study confirmed that the noncovalent interactions between the chalcogen bond and Sn salt were pivotal for achieving regioselectivity. This synthetic method was applied for the development of potent and highly selective positron emission tomography molecular probes for serotonin transporters.

Hydrothermal carbonisation of polyvinyl chloride in ethanol-water/water system for solid fuels: Dechlorination, characteristics analysis of hydrochar, and reaction path.

Polyvinyl chloride (PVC) waste plastic is a typical solid waste. In this paper, the dechlorination and carbonization behavior of PVC in ethanol-water/water system under different process parameters (temperature, residence time, solid-liquid ratio) was studied, and hydrothermal carbon was characterized by SEM, elemental analysis, TG-DTG, XPS, Py-GC/MS. The results show that temperature is the key to the hydrothermal dechlorination of PVC, and the dechlorination efficiency of PVC is the highest by parameter optimization (220°C-90 min-10% S/D-80% E/D), which can reach 96.33 %. With the removal of Cl, the surface of the PVC matrix changed from full and smooth flocculent to honeycomb with uniform pore size distribution. Thermogravimetric analysis shows that the combustion of hydrochar can be divided into three stages: HCl precipitation and volatile combustion, semi-coke and coke combustion, and fixed carbon combustion. The combustion parameters and kinetic parameters of hydrochar were measured, and it was found that the hydrothermal carbonization of PVC at higher temperatures and ethanol-water ratio could improve the combustion performance of hydrochar. The highest calorific value can reach 36.68 MJ/mol. Py-GC/MS analyzed the distribution of the pyrolysis products, and alkylbenzene and aliphatic were the main products of pyrolysis. The structural analysis of hydrochar showed that C-C and CC accounted for the largest proportion, accompanied by a small amount of C-O and CO and trace C-Cl. The possible reaction mechanism of the hydrothermal carbonization of PVC was analyzed based on the distribution of functional groups and compound composition. This work provides an effective and sustainable method for the recycling of refractory chlorinated plastics.

Preparation of functionalized porous chitin carbon to enhance the H2O2 production and Fe3+ reduction properties of Electro-Fenton cathodes for efficient degradation of RhB.

The performance of Electro-Fenton (EF) cathode materials is primarily assessed by H2O2 yield and Fe3+ reduction efficiency. This study explores the impact of pore structure in chitin-based porous carbon on EF cathode effectiveness. We fabricated mesoporous carbon (CPC-700-2) and microporous carbon (ZPC-700-3) using template and activation methods, retaining nitrogen from the precursors. CPC-700-2, with mesopores (3-5 nm), enhanced O2 diffusion and oxygen reduction, producing up to 778 mg/L of H2O2 in 90 min. ZPC-700-3, with a specific surface area of 1059.83 m2/g, facilitated electron transport and ion diffusion, achieving a Fe2+/Fe3+ conversion rate of 79.9%. EF systems employing CPC-700-2 or ZPC-700-3 as the cathode exhibited superior degradation performance, achieving 99% degradation of Rhodamine B, efficient degradation, and noticeable decolorization. This study provides a reference for the preparation of functionalized carbon cathode materials for efficient H2O2 production and effective Fe3+ reduction in EF systems.

Deep-learning reconstruction of complex dynamical networks from incomplete data.

Reconstructing complex networks and predicting the dynamics are particularly challenging in real-world applications because the available information and data are incomplete. We develop a unified collaborative deep-learning framework consisting of three modules: network inference, state estimation, and dynamical learning. The complete network structure is first inferred and the states of the unobserved nodes are estimated, based on which the dynamical learning module is activated to determine the dynamical evolution rules. An alternating parameter updating strategy is deployed to improve the inference and prediction accuracy. Our framework outperforms baseline methods for synthetic and empirical networks hosting a variety of dynamical processes. A reciprocity emerges between network inference and dynamical prediction: better inference of network structure improves the accuracy of dynamical prediction, and vice versa. We demonstrate the superior performance of our framework on an influenza dataset consisting of 37 US States and a PM2.5 dataset covering 184 cities in China.

Research progress in improving sludge dewaterability: sludge characteristics, chemical conditioning and influencing factors.

Sludge from wastewater treatment processes with high water content and large volume has become an inevitable issue in environmental management. Due to the challenging dewatering properties of sludge, current mechanical dewatering methods are no longer sufficient to meet the escalating water content standards of sludge. This paper summarizes the characteristics of various sludge and raises reasons for the their dewaterability differences. Affected by extracellular polymeric substances, biological sludge is hydrophilic and negatively charged, which limits the dewatering degree. The rheological properties, flocs, ionic composition, and solid phase concentration of the sludge also influence the dewatering to some extent. For these factors, the chemical conditioning measures with simple operation and excellent effect improve its dewaterability, which mainly include flocculation/coagulation, acid/alkali treatment, advanced oxidation, surfactant treatment and combined treatment. There is a growing necessity to explore the development of new chemical conditioning agents, even though traditional agents continue to remain widely used. However, the development of these new agents should prioritize finding a balance between various factors such as efficiency, effectiveness, ease of operation, environmental safety, and cost-effectiveness. Electrochemical dewatering enhances solid-liquid separation, and its coupling with chemical conditioning is also an excellent means to further reduce water content. In addition, the improvement of press filter is an effective way, which is influenced by pressure, processing time, sludge cake thickness and pore structure, filter media etc. In general, it is essential to develop new conditioning agents and enhance mechanical filtration press technology based on a thorough understanding of various sludge properties. Concurrently, an in-depth study of the principles of mechanical pressure filtration will contribute to establishing a theoretical foundation for effective deep sludge dewatering and propel further advancements in this field.

Construction of a Flexible Optogenetic Device for Multisite and Multiregional Optical Stimulation Through Flexible µ-LED Displays on the Cerebral Cortex.

Precisely delivering light to multiple locations in biological tissue is crucial for advancing multiregional optogenetics in neuroscience research. However, conventional implantable devices typically have rigid geometries and limited light sources, allowing only single or dual probe placement with fixed spacing. Here, a fully flexible optogenetic device with multiple thin-film microscale light-emitting diode (µ-LED) displays scattering from a central controller is presented. Each display is heterogeneously integrated with thin-film 5 × 10 µ-LEDs and five optical fibers 125 µm in diameter to achieve cellular-scale spatial resolution. Meanwhile, the device boasts a compact, flexible circuit capable of multichannel configuration and wireless transmission, with an overall weight of 1.31 g, enabling wireless, real-time neuromodulation of freely moving rats. Characterization results and finite element analysis have demonstrated excellent optical properties and mechanical stability, while cytotoxicity tests further ensure the biocompatibility of the device for implantable applications. Behavior studies under optogenetic modulation indicate great promise for wirelessly modulating neural functions in freely moving animals. The device with multisite and multiregional optogenetic modulation capability offers a comprehensive platform to advance both fundamental neuroscience studies and potential applications in brain-computer interfaces.

Orthant-symmetric four-dimensional geometric shaping for fiber-optic channels via a nonlinear interference model.

Maximizing the data throughput for optical fiber communication via signal shaping has usually been regarded as challenging due to the nonlinear interference and implementation/optimization complexity. To overcome these challenges, in this paper, we propose an efficient four-dimensional (4D) geometric shaping (GS) approach to design 4D 512-ary and 1024-ary modulation formats by maximizing the generalized mutual information (GMI) using a 4D nonlinear interference (NLI) model, which makes these modulation formats more nonlinear-tolerant. In addition, we propose and evaluate a fast and low-complexity orthant-symmetry based modulation optimization algorithm via neural networks, which allows to improve the optimization speed and GMI performance for both linear and nonlinear fiber transmission systems. The optimized modulation formats with spectral efficiencies of 9 and 10 bit/4D-sym demonstrate a GMI improvement of up to 1.35 dB compared with their quadrature amplitude modulation (QAM) counterparts in additive white Gaussian noise (AWGN) channel. Numerical simulations of optical transmission over two types of fibers show that the 4D NLI model-learned modulation formats could extend the transmission reach by up to 34% and 12% with respect to the QAM formats and the AWGN-learned 4D modulation formats, respectively. Results of effective signal-to-noise ratio are also presented, which confirm that the extra gains in optical fiber channel come from the enhanced SNR by reducing the modulation-dependent NLI.

Maternal and Paternal Dietary Quality and Dietary Inflammation Associations with Offspring DNA Methylation and Epigenetic Biomarkers of Aging in the Lifeways Cross-Generation Study.

BACKGROUND: Early-life nutritional exposures may contribute to offspring epigenetic modifications. However, few studies have evaluated parental dietary quality effects on offspring DNA methylation (DNAm). OBJECTIVES: We aim to fill this gap by elucidating the influence of maternal and paternal whole-diet quality and inflammatory potential on offspring DNAm in the Lifeways Cross-generation cohort. METHODS: Families (n = 1124) were recruited around 16 weeks of gestation in the Republic of Ireland between 2001 and 2003. Maternal dietary intake during the first trimester and paternal diet during the 12 previous months were assessed with an FFQ. Parental dietary inflammatory potential and quality were determined using the energy-adjusted Dietary Inflammatory Index (E-DII), the Healthy Eating Index-2015 (HEI-2015), and the maternal DASH score. DNAm in the saliva of 246 children at age nine was measured using the Illumina Infinium HumanMethylationEPIC array. DNAm-derived biomarkers of aging, the Pediatric-Buccal-Epigenetic clock and DNAm estimator of telomere length, were calculated. Parental diet associations with the DNAm concentrations of 850K Cytosine-phosphate-guanine sites (CpG sites) and with DNAm-derived biomarkers of aging were examined using an epigenome-wide association study and linear regressions, respectively. RESULTS: Maternal HEI-2015 scores were inversely associated with DNAm at CpG site (cg21840035) located near the PLEKHM1 gene, whose functions involve regulation of bone development (ß = -0.0036, per 1 point increase in the score; P = 5.6 × 10-8). Higher paternal HEI-2015 score was related to lower methylation at CpG site (cg22431767), located near cell signaling gene LUZP1 (ß = -0.0022, per 1 point increase in the score, P = 4.1 × 10-8). There were no associations with parental E-DII and DASH scores, and no evidence of major effects on biomarkers of aging. CONCLUSIONS: Parental dietary quality in the prenatal period, evaluated by the HEI-2015, may influence offspring DNAm during childhood. Further research to improve our understanding of parental nutritional programming is warranted.

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial.

BACKGROUND: Aponermin, a circularly permuted tumor necrosis factor-related apoptosis-inducing ligand, is a potential death receptor 4/5-targeted antitumour candidate. Previous phase 1/2 studies have demonstrated the efficacy of aponermin in patients with relapsed or refractory multiple myeloma (RRMM). To confirm the superiority of aponermin plus thalidomide and dexamethasone (aponermin group) over placebo plus thalidomide and dexamethasone (placebo group) in RRMM, a randomized, double-blinded, placebo controlled phase 3 trial was performed. METHODS: Four hundred seventeen patients with RRMM who had previously received at least two regimens were randomly assigned (2:1) to receive aponermin, thalidomide, and dexamethasone or placebo, thalidomide, and dexamethasone. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and overall response rate (ORR). RESULTS: A total of 415 patients received at least one dose of trial treatment (276 vs. 139). The median PFS was 5.5 months in the aponermin group and 3.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.49-0.78; P < 0.001). The median OS was 22.4 months for the aponermin group and 16.4 months for the placebo group (hazard ratio, 0.70; 95% CI, 0.55-0.89; P = 0.003). Significantly higher rates of ORR (30.4% vs. 13.7%, P < 0.001) and very good partial response or better (14.1% vs. 2.2%, P < 0.0001) were achieved in the aponermin group than in the placebo group. Treatment with aponermin caused hepatotoxicity in some patients, as indicated by the elevated alanine transaminase, aspartate transaminase, or lactate dehydrogenase levels (52.2% vs. 24.5%, 51.1% vs. 19.4% and 44.9% vs. 21.6%, respectively), mostly grade 1/2, transient and reversible. The main grade 3/4 adverse events included neutropenia, pneumonia and hyperglycemia. The incidence of serious adverse events was similar between the two groups (40.6% vs. 37.4%). There was no evidence that aponermin leads to hematological toxicity, nephrotoxicity, cardiotoxicity, or secondary tumors. CONCLUSIONS: Aponermin plus thalidomide and dexamethasone significantly improved PFS, OS and ORR with manageable side effects in RRMM patients who had received at least two prior therapies. These results support the use of aponermin, thalidomide, and dexamethasone as a treatment option for RRMM patients. TRIAL REGISTRATION: The trial was registered at http://www.chictr.org.cn as ChiCTR-IPR-15006024, 17/11/2014.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

The Role of Open Cardiopulmonary Resuscitation in Chest Trauma Patients with No Sign of Life: A National Trauma Data Bank Study.

PURPOSE: The effectiveness of open cardiopulmonary resuscitation (OCPR) remains controversial for trauma patients. In this current study, the role of OCPR in managing chest trauma patients is evaluated using nationwide real-world data. METHODS: From 2014 to 2015, the National Trauma Data Bank was retrospectively queried for chest trauma patients with out-of-hospital cardiac arrest status. The emergency department (ED) and overall survival of patients without signs of life were analyzed. Multivariate logistic regression (MLR) analysis was performed to evaluate independent factors of mortality for the target group. Furthermore, a subset group of patients who survived after the ED were studied, focusing on the duration of survival after leaving the ED. RESULTS: A total of 911 patients were enrolled in this study (OCPR vs. non-OCPR: 161 patients vs. 750 patients). The average overall mortality rate was 98.6% (N = 898). Among penetrating chest trauma patients, non-survivors in the ED had significantly higher proportions of gunshot injuries (83.9% vs. 69.7%, p = 0.001) and lower proportions of OCPR (20.7% vs. 44.4%, p < 0.001). MLR analysis showed that gunshot injuries and non-OCPR were significantly related to ED mortality in penetrating trauma patients without signs of life (odds ratio = 2.039, p = 0.006 and odds ratio = 2.900, p < 0.001, respectively). However, the overall survival rate of patients after ED survival (n = 99) was 9.9%, and only 21.2% (n = 21) of them survived more than 1 day after leaving the ED. CONCLUSION: OCPR could be considered in situations where appropriate indications exist. The survival benefit was observed in critically ill patients with penetrating chest trauma who show no signs of life. By enhancing ED survival, OCPR may also contribute to overall survival improvement.

Comparing the effectiveness of two diagnostic approaches for the interpretation of oral radiographic lesions by dental students.

Interpreting radiographic lesions on dental radiographs is a challenging process especially for novice learners, and there is a lack of tools available to support this diagnostic process. This study introduced dental students to two diagnostic aids with contrasting reasoning approaches-ORAD DDx, which uses an analytic, forward reasoning approach, and a Radiographic Atlas, which emphasizes a non-analytic, backward reasoning approach. We compared the effectiveness of ORAD DDx and the Atlas in improving students' diagnostic accuracy and their ability to recall features of radiographic lesions. Participants (99 third-year dental students) were assigned to ORAD DDx, Atlas and Control groups. In the pre-test and post-test, participants provided their diagnosis for eight types of radiographic lesions. All groups also completed a Cued Recall Test. Feedback about ORAD DDx and the Atlas was collected. Results indicated that the Atlas was more effective than ORAD DDx in improving diagnostic accuracy (Estimated marginal mean difference = 1.88 (95% CI 0.30-3.46), p = 0.014, Cohen's d = 0.714). Participants in the Atlas group also outperformed the Control group in the recall of the lesions' radiographic features (Estimated marginal mean difference = 3.42 (95% CI 0.85-5.99), p = 0.005, Cohen's d = 0.793). Students reported that both ORAD DDx and Atlas increased their confidence and decreased the mental effort required to develop differential diagnosis (p ≤ 0.001). This study demonstrates the effectiveness of a non-analytic approach in interpreting dental radiographs among novice learners through the novel use of diagnostic aids.

Synthesis and biological evaluation of C-4 substituted phenoxazine-bearing hydroxamic acids with potent class II histone deacetylase inhibitory activities.

Class II histone deacetylases (HDACs) are considered as potential targets to treat Alzheimer's disease (AD). Previously, C-3 substituted phenothiazine-containing compounds with class II HDAC-inhibiting activities was found to promote neurite outgrowth. This study replaced phenothiazine moiety with phenoxazine that contains many C-3 and C-4 substituents. Some resulting compounds bearing the C-4 substituent on a phenoxazine ring displayed potent class II HDAC inhibitory activities. Structure-activity relationship (SAR) of these compounds that inhibited HDAC isoenzymes was disclosed. Molecular modelling analysis demonstrates that the potent activities of C-4 substituted compounds probably arise from π-π stacked interactions between these compounds and class IIa HDAC enzymes. One of these, compound 7d exhibited the most potent class II HDAC inhibition (IC50= 3-870 nM). Notably, it protected neuron cells from H2O2-induced neuron damage at sub-µM concentrations, but with no significant cytotoxicity. These findings show that compound 7d is a lead compound for further development of anti-neurodegenerative agents.

Short-lived chimera states.

In the classic Kuramoto system of coupled two-dimensional rotators, chimera states characterized by the coexistence of synchronous and asynchronous groups of oscillators are long-lived because the average lifetime of these states increases exponentially with the system size. Recently, it was discovered that, when the rotators in the Kuramoto model are three-dimensional, the chimera states become short-lived in the sense that their lifetime scales with only the logarithm of the dimension-augmenting perturbation. We introduce transverse-stability analysis to understand the short-lived chimera states. In particular, on the unit sphere representing three-dimensional (3D) rotations, the long-lived chimera states in the classic Kuramoto system occur on the equator, to which latitudinal perturbations that make the rotations 3D are transverse. We demonstrate that the largest transverse Lyapunov exponent calculated with respect to these long-lived chimera states is typically positive, making them short-lived. The transverse-stability analysis turns the previous numerical scaling law of the transient lifetime into an exact formula: the "free" proportional constant in the original scaling law can now be precisely determined in terms of the largest transverse Lyapunov exponent. Our analysis reinforces the speculation that in physical systems, chimera states can be short-lived as they are vulnerable to any perturbations that have a component transverse to the invariant subspace in which they live.

Reservoir computing as digital twins for nonlinear dynamical systems.

We articulate the design imperatives for machine learning based digital twins for nonlinear dynamical systems, which can be used to monitor the "health" of the system and anticipate future collapse. The fundamental requirement for digital twins of nonlinear dynamical systems is dynamical evolution: the digital twin must be able to evolve its dynamical state at the present time to the next time step without further state input-a requirement that reservoir computing naturally meets. We conduct extensive tests using prototypical systems from optics, ecology, and climate, where the respective specific examples are a chaotic CO2 laser system, a model of phytoplankton subject to seasonality, and the Lorenz-96 climate network. We demonstrate that, with a single or parallel reservoir computer, the digital twins are capable of a variety of challenging forecasting and monitoring tasks. Our digital twin has the following capabilities: (1) extrapolating the dynamics of the target system to predict how it may respond to a changing dynamical environment, e.g., a driving signal that it has never experienced before, (2) making continual forecasting and monitoring with sparse real-time updates under non-stationary external driving, (3) inferring hidden variables in the target system and accurately reproducing/predicting their dynamical evolution, (4) adapting to external driving of different waveform, and (5) extrapolating the global bifurcation behaviors to network systems of different sizes. These features make our digital twins appealing in applications, such as monitoring the health of critical systems and forecasting their potential collapse induced by environmental changes or perturbations. Such systems can be an infrastructure, an ecosystem, or a regional climate system.

Mechanism of the Anti-Influenza Functions of Guizhi Granules Based on Network Pharmacology, Molecular Docking, and in Vitro Experiments.

Guizhi granules mainly treat colds and improve overall health. They are widely used in clinical practice, but their protective effect and anti-inflammatory mechanism against influenza are unclear. In this study, the therapeutic effect of Guizhi granules on influenza was verified in vitro. The active compounds, targets, and cellular pathways of Guizhi granules against influenza were predicted using network pharmacology. The protein-protein interaction and component-target networks identified 5 core targets (JUN, TNF-α, RELA, AKT1, and MAPK1) and components (dihydrocapsaicin, kumatakenin, calycosin, licochalcone A, and berberine). GO and KEGG enrichment analyses revealed the anti-influenza pathways of Guizhi granules as antiviral and anti-inflammatory pathways. Molecular docking further verified that the core targets and components have good or strong binding activity. Therefore, the active ingredients, targets, and molecular mechanisms of Guizhi granules involved in influenza treatment were elucidated.

Clinical observation of Porcine Collagen Membrane + artificial Bovine Bone Granules Guided tissue regeneration combined with Autologous CGF in the treatment of severe periodontitis bone defect.

Objective: To investigate and analyze the clinical observation of porcine collagen membrane + artificial bovine bone granules guided tissue regeneration (GTR) combined with autologous concentration of growth factors (CGF) in the treatment of severe periodontitis bone defect. Methods: A total of 94 patients with severe periodontitis bone defects admitted to Shanxi Bethune Hospital from January 2019 to January 2022 were included. They were divided into two groups by simple randomization method. Patients in the control group were treated with porcine collagen membrane + artificial bovine bone granules GTR, while those in the observation group were treated with autologous CGF on the basis of the control group. Before and after treatment, periodontal clinical indicators [sulcus bleeding index (SBI), gingival retreat index (GR), probing depth (PD), clinical attachment loss (CAL), alveolar bone height (AH)] and bone resorption markers [Osteoprotegerin (OPG), bone gla protein (BGP), Type-1 collagen N-terminal peptide (NTX)] were compared between the two groups, and the incidence of postoperative complications in the two groups was recorded. Results: The total efficacy of observation group was significantly higher than that of control group (p<0.05). Three months after surgery, the observation group had lower levels of SBI, PD, CAL and NTX while higher levels of GR, AH, OPG and BGP than the control group (p<0.05). There was no significant difference in complication rate between the two groups (p>0.05). Conclusion: Porcine collagen membrane + artificial bovine bone granules GTR combined with autologous CGF boasts various benefits in the treatment of severe periodontitis bone defects, such as improvement of clinical outcomes, amelioration of periodontal tissue and inhibition of bone resorption.

[Identification of terpene synthase gene family in Gynostemma pentaphyllum and expression pattern analysis under abiotic stresses].

The present study aimed to investigate the composition of the terpene synthase(TPS) gene family in Gynostemma pentaphyllum and its role in abiotic stresses. The G. pentaphyllum TPS gene family was identified and analyzed at the genome-wide level using bioinformatics analysis, and the expression patterns of these family members were analyzed in different tissues of G. pentaphyllum as well as under various abiotic stresses. The results showed that there were 24 TPS gene family members in G. pentaphyllum with protein lengths ranging from 294 to 842 aa. All of them were localized in the cytoplasm or chloroplasts and unevenly distributed on the 11 chromosomes of G. pentaphyllum. The results of the phylogenetic tree showed that the G. pentaphyllum TPS gene family members could be divided into five subfamilies. As revealed by the analysis of promoter cis-acting elements, TPS gene family members in G. pentaphyllum were predicted to respond to a variety of abiotic stresses such as salt, low temperature, and dark stress. The analysis of gene expression patterns in different tissues of G. pentaphyllum revealed that nine TPS genes were tissue-specific in expression. The qPCR results showed that GpTPS16, GpTPS17, and GpTPS21 responded to a variety of abiotic stresses. This study is expected to provide references in guiding the further exploration of the biological functions of G. pentaphyllum TPS genes under abiotic stresses.