Construction and validation of a risk prediction model for extrauterine growth restriction in preterm infants born at gestational age less than 34 weeks.

Objective: This study aimed to develop and validate a model for predicting extrauterine growth restriction (EUGR) in preterm infants born ≤34 weeks gestation. Methods: Preterm infants from Guangxi Maternal and Child Health Hospital (2019-2021) were randomly divided into training (80%) and testing (20%) sets. Collinear clinical variables were excluded using Pearson correlation coefficients. Predictive factors were identified using Lasso regression. Random forest (RF), support vector machine (SVM), and logistic regression (LR) models were then built and evaluated using the confusion matrix, area under the curve (AUC), and the F1 score. Additionally, calibration curves and decision curve analysis (DCA) were plotted to assess the performance and practical utility of the models. Results: The study included 387 infants, with no significant baseline differences between training (n = 310) and testing (n = 77) sets. LR identified gestational age, birth weight, premature rupture of membranes, patent ductus arteriosus, cholestasis, and neonatal sepsis as key EUGR predictors. The RF model (19 variables) demonstrated an accuracy of greater than 90% during training, and superior AUC (0.62), F1 score (0.80), and accuracy (0.72) in testing compared to other models. Conclusions: Gestational age, birth weight, premature rupture of membranes, patent ductus arteriosus, cholestasis, and neonatal sepsis are significant EUGR predictors in preterm infants ≤34 weeks. The model shows promise for early EUGR prediction in clinical practice, potentially enhancing screening efficiency and accuracy, thus saving medical resources.

All-Cellulose-based flexible Zinc-Ion battery enabled by waste pomelo peel.

Aqueous zinc-ion batteries are attracting extensive attention due to the long-term service life and credible safety as well as the superior price performance between the low cost of manufacture and high energy density. The fabrication of inexpensive, high-performance flexible solid-state zinc-ion batteries, thus, are urgently need for the blooming wearable electronics. Herein, as a proof-of-concept study of waste into wealth, cellulose flakes derived from waste pomelo peel are utilized as the substrate for electrodes and hydrogel electrolytes into a flexible rocking-chair zinc-ion battery. The unique sandwich-type structure holding the flake-like cellulose substrate and linear carbon nanotubes endows the flexible cathode and anode with fast ion and electron transportation. The obtained cellulose-based hydrogel electrolytes on account of special affinity with aqueous ZnSO4 electrolyte output an excellent ionic conductivity. The assembled flexible rocking-chair zinc-ion battery benefitting from the synergistic effect of sandwich-type electrodes and cellulose-based hydrogel electrolytes demonstrates outstanding electrochemical performance and mechanical properties. This work not only puts up an effective roadmap for flexible battery devices, but also reveals the great potential of waste biomass materials in energy storage applications.

Sex-Specific Behavioral and Molecular Responses to Maternal Lipopolysaccharide-Induced Immune Activation in a Murine Model: Implications for Neurodevelopmental Disorders.

Maternal immune activation (MIA) during pregnancy has been increasingly recognized as a critical factor in the development of neurodevelopmental disorders, with potential sex-specific impacts that are not yet fully understood. In this study, we utilized a murine model to explore the behavioral and molecular consequences of MIA induced by lipopolysaccharide (LPS) administration on embryonic day 12.5. Our findings indicate that male offspring exposed to LPS exhibited significant increases in anxiety-like and depression-like behaviors, while female offspring did not show comparable changes. Molecular analyses revealed alterations in pro-inflammatory cytokine levels and synaptic gene expression in male offspring, suggesting that these molecular disruptions may underlie the observed behavioral differences. These results emphasize the importance of considering sex as a biological variable in studies of neurodevelopmental disorders and highlight the need for further molecular investigations to understand the mechanisms driving these sex-specific outcomes. Our study contributes to the growing evidence that prenatal immune challenges play a pivotal role in the etiology of neurodevelopmental disorders and underscores the potential for sex-specific preventative approaches of MIA.

Integrated Effects of Soil Moisture on Wheat Hydraulic Properties and Stomatal Regulation.

The development of water-saving management relies on understanding the physiological response of crops to soil drought. The coordinated regulation of hydraulics and stomatal conductance in plant water relations has steadily received attention. However, research focusing on grain crops, such as winter wheat, remains limited. In this study, three soil water supply treatments, including high (H), moderate (M), and low (L) soil water contents, were conducted with potted winter wheat. Leaf water potential (Ψleaf), leaf hydraulic conductance (Kleaf), and stomatal conductance (gs), as well as leaf biochemical parameters and stomatal traits were measured. Results showed that, compared to H, predawn leaf water potential (ΨPD) significantly reduced by 48.10% and 47.91%, midday leaf water potential (ΨMD) reduced by 40.71% and 43.20%, Kleaf reduced by 64.80% and 65.61%, and gs reduced by 21.20% and 43.41%, respectively, under M and L conditions. Although gs showed a significant difference between M and L, Ψleaf and Kleaf did not show significant differences between these treatments. The maximum carboxylation rate (Vcmax) and maximum electron transfer rate (Jmax) under L significantly decreased by 23.11% and 28.10%, stomatal density (SD) and stomatal pore area index (SPI) under L on the abaxial side increased by 59.80% and 52.30%, respectively, compared to H. The leaf water potential at 50% hydraulic conduction loss (P50) under L was not significantly reduced. The gs was positively correlated with ΨMD and Kleaf, but it was negatively correlated with abscisic acid (ABA) and SD. A threshold relationship between gs and Kleaf was observed, with rapid and linear reduction in gs occurring only when Kleaf fell below 8.70 mmol m-2 s-1 MPa-1. Our findings demonstrate that wheat leaves adapt stomatal regulation strategies from anisohydric to isohydric in response to reduced soil water content. These results enrich the theory of trade-offs between the carbon assimilation and hydraulic safety in crops and also provide a theoretical basis for water management practices based on stomatal regulation strategies under varying soil water conditions.

MixImages: An Urban Perception AI Method Based on Polarization Multimodalities.

Intelligent urban perception is one of the hot topics. Most previous urban perception models based on semantic segmentation mainly used RGB images as unimodal inputs. However, in natural urban scenes, the interplay of light and shadow often leads to confused RGB features, which diminish the model's perception ability. Multimodal polarization data encompass information dimensions beyond RGB, which can enhance the representation of shadow regions, serving as additional data for assistance. Additionally, in recent years, transformers have achieved outstanding performance in visual tasks, and their large, effective receptive field can provide more discriminative cues for shadow regions. For these reasons, this study proposes a novel semantic segmentation model called MixImages, which can combine polarization data for pixel-level perception. We conducted comprehensive experiments on a polarization dataset of urban scenes. The results showed that the proposed MixImages can achieve an accuracy advantage of 3.43% over the control group model using only RGB images in the unimodal benchmark while gaining a performance improvement of 4.29% in the multimodal benchmark. Additionally, to provide a reference for specific downstream tasks, we also tested the impact of different combinations of polarization types on the overall segmentation accuracy. The proposed MixImages can be a new option for conducting urban scene perception tasks.

Retarding the capacity fading and voltage decay of Li-rich Mn-based cathode materials via a compatible layer coating for high-performance lithium-ion batteries.

Li-rich Mn-based layered oxides have been considered as the most promising cathode candidate for high energy density lithium ion batteries. However, the practical application of Li-rich Mn-based layered oxides is hindered due to the capacity fading and voltage decay accompanied with structure transition from the layered structure to spinel phase during cycling. Herein, a facile surface structure repair via Ce modification is reported. The structural analysis of the bulk and coating layer was carried out using XRD, XPS, SEM and TEM, which confirmed the successful doping of Ce and formation of a Li2CeO3 coating on the surface. The modified sample LLO-2 delivers a discharge specific capacity of 263.5 mA h g-1 at 0.1C and capacity retention rate with 88.1% at 0.2C after 100 cycles compared to 250.2 mA h g-1 and 75.6% for the pristine sample. The enhanced performance could be because Ce doping enlarges the lattice parameter, which may contribute to accelerating the Li+ diffusion rate. Moreover, the newly formed Li2CeO3 coating with oxygen vacancies could inhibit the loss of lattice oxygen and protect the electrode surface by suppressing the attack from the electrolyte. This work provides an effective approach to design Li-rich Mn-based layered oxides with improved electrochemical performance.

Network pharmacology and molecular dynamics study of the effect of the Astragalus-Coptis drug pair on diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The Astragalus-Coptis drug pair is frequently employed in the management of DKD. However, the precise molecular mechanism underlying its therapeutic effect remains elusive. AIM: To investigate the synergistic effects of multiple active ingredients in the Astragalus-Coptis drug pair on DKD through multiple targets and pathways. METHODS: The ingredients of the Astragalus-Coptis drug pair were collected and screened using the TCMSP database and the SwissADME platform. The targets were predicted using the SwissTargetPrediction database, while the DKD differential gene expression analysis was obtained from the Gene Expression Omnibus database. DKD targets were acquired from the GeneCards, Online Mendelian Inheritance in Man database, and DisGeNET databases, with common targets identified through the Venny platform. The protein-protein interaction network and the "disease-active ingredient-target" network of the common targets were constructed utilizing the STRING database and Cytoscape software, followed by the analysis of the interaction relationships and further screening of key targets and core active ingredients. Gene Ontology (GO) function and Kyoto Ency-clopedia of Genes and Genomes (KEGG) pathway enrichments were performed using the DAVID database. The tissue and organ distributions of key targets were evaluated. PyMOL and AutoDock software validate the molecular docking between the core ingredients and key targets. Finally, molecular dynamics (MD) simulations were conducted to simulate the optimal complex formed by interactions between core ingredients and key target proteins. RESULTS: A total of 27 active ingredients and 512 potential targets of the Astragalus-Coptis drug pair were identified. There were 273 common targets between DKD and the Astragalus-Coptis drug pair. Through protein-protein interaction network topology analysis, we identified 9 core active ingredients and 10 key targets. GO and KEGG pathway enrichment analyses revealed that Astragalus-Coptis drug pair treatment for DKD involves various biological processes, including protein phosphorylation, negative regulation of apoptosis, inflammatory response, and endoplasmic reticulum unfolded protein response. These pathways are mainly associated with the advanced glycation end products (AGE)-receptor for AGE products signaling pathway in diabetic complications, as well as the Lipid and atherosclerosis. Molecular docking and MD simulations demonstrated high affinity and stability between the core active ingredients and key targets. Notably, the quercetin-AKT serine/threonine kinase 1 (AKT1) and quercetin-tumor necrosis factor (TNF) protein complexes exhibited exceptional stability. CONCLUSION: This study demonstrated that DKD treatment with the Astragalus-Coptis drug pair involves multiple ingredients, targets, and signaling pathways. We propose a novel approach for investigating the molecular mechanism underlying the therapeutic effects of the Astragalus-Coptis drug pair on DKD. Furthermore, we suggest that quercetin is the most potent active ingredient and specifically targets AKT1 and TNF, providing a theoretical foundation for further exploration of pharmacologically active ingredients and elucidating their molecular mechanisms in DKD treatment.

Physiological and genetic responses of the benthic dinoflagellate Prorocentrum lima to polystyrene microplastics.

Microplastics are well known as contaminants in marine environments. With the development of biofilms, most microplastics will eventually sink and deposit in benthic environment. However, little research has been done on benthic toxic dinoflagellates, and the effects of microplastics on benthic dinoflagellates are unknown. Prorocentrum lima is a cosmopolitan toxic benthic dinoflagellate, which can produce a range of polyether metabolites, such as diarrhetic shellfish poisoning (DSP) toxins. In order to explore the impact of microplastics on marine benthic dinoflagellates, in this paper, we studied the effects of polystyrene (PS) on the growth and toxin production of P. lima. The molecular response of P. lima to microplastic stress was analyzed by transcriptomics. We selected 100 nm, 10 µm and 100 µm PS, and set three concentrations of 1 mg L-1, 10 mg L-1 and 100 mg L-1. The results showed that PS exposure had limited effects on cell growth, but increased the OA and extracellular polysaccharide content at high concentrations. After exposure to PS MPs, genes associated with DSP toxins synthesis, carbohydrate synthesis and energy metabolism, such as glycolysis, TCA cycle and pyruvate metabolism, were significantly up-regulated. We speculated that after exposure to microplastics, P. lima may increase the synthesis of DSP toxins and extracellular polysaccharides, improve the level of energy metabolism and gene expression of ABC transporter, thereby protecting algal cells from damage. Our findings provide new insights into the effects of microplastics on toxic benthic dinoflagellates.

Phosphoric Acid-Catalyzed Alkene Difunctionalization of 2-Vinylpyridines via HOMO/LUMO Biactivated Diels-Alder Reaction.

The difunctionalization of vinylpyridines based on the cyclization strategy remains rare and underdeveloped, in contrast to the well-developed hydrogen functionalization. Current exploration on [4 + 2] cyclization of vinylpyridines mainly relies on extremely high temperatures and the LUMO activation of vinylpyridines using boron trifluoride as a strong Lewis acid. Herein, we established a phosphoric acid-catalyzed [4 + 2] cyclization reaction of 3-vinyl-1H-indoles and 2-vinylpyridines by means of the LUMO/HOMO bifunctional activation model. This protocol features mild reaction conditions, high functional group tolerance, broad substrate compatibility, and high diastereoselectivity, enabling the efficient construction of various functionalized pyridine-substituted tetrahydrocarbazoles with prominent potential in drug discovery.

Prevalence of nontuberculous mycobacteria and the emergence of rare species in Henan Province, China.

Nontuberculous mycobacteria (NTM) is a large group of mycobacteria other than the Mycobacterium tuberculosis complex and Mycobacterium leprae. Epidemiological investigations have found that the incidence of NTM infections is increasing in China, and it is naturally resistant to many antibiotics. Therefore, studies of NTM species in clinical isolates are useful for understanding the epidemiology of NTM infections. The present study aimed to investigate the incidence of NTM infections and types of NTM species. Of the 420 samples collected, 285 were positive for M. tuberculosis, 62 samples were negative, and the remaining 73 samples contained NTM, including 35 (8.3%) only NTM and 38 (9%) mixed (M. tuberculosis and NTM). The most prevalent NTM species were Mycobacterium intracellulare (30.1%), followed by Mycobacterium abscessus (15%) and M. triviale (12%). M. gordonae infection was detected in 9.5% of total NTM-positive cases. Moreover, this study reports the presence of Mycobacterium nonchromogenicum infection and a high prevalence of M. triviale for the first time in Henan. M. intracellulare is the most prevalent, accompanied by some emerging NTM species, including M. nonchromogenicum and a high prevalence of M. triviale in Henan Province. Monitoring NTM transmission and epidemiology could enhance mycobacteriosis management in future.

BET bromodomain inhibition potentiates radiosensitivity in models of H3K27-altered diffuse midline glioma.

Diffuse midline glioma (DMG) H3K27-altered is one of the most malignant childhood cancers. Radiation therapy remains the only effective treatment yet provides a 5-year survival rate of only 1%. Several clinical trials have attempted to enhance radiation antitumor activity using radiosensitizing agents, although none have been successful. Given this, there is a critical need for identifying effective therapeutics to enhance radiation sensitivity for the treatment of DMG. Using high-throughput radiosensitivity screening, we identified bromo- and extraterminal domain (BET) protein inhibitors as potent radiosensitizers in DMG cells. Genetic and pharmacologic inhibition of BET bromodomain activity reduced DMG cell proliferation and enhanced radiation-induced DNA damage by inhibiting DNA repair pathways. RNA-Seq and the CUT&RUN (cleavage under targets and release using nuclease) analysis showed that BET bromodomain inhibitors regulated the expression of DNA repair genes mediated by H3K27 acetylation at enhancers. BET bromodomain inhibitors enhanced DMG radiation response in patient-derived xenografts as well as genetically engineered mouse models. Together, our results highlight BET bromodomain inhibitors as potential radiosensitizer and provide a rationale for developing combination therapy with radiation for the treatment of DMG.

MED1 IDR acetylation reorganizes the transcription preinitiation complex, rewires 3D chromatin interactions and reprograms gene expression.

With our current appreciation of the complexity of eukaryotic transcription, whose dysregulation drives diseases including cancer, it is becoming apparent that identification of key events coordinating multiple aspects of transcriptional regulation is of special importance. To elucidate how assembly of RNA polymerase II (Pol II) with Mediator complex preinitiation complexes (PICs) and formation of transcription-permissive 3D chromatin organization are coordinated, we studied MED1, a representative subunit of the Mediator complex that acts to establish functional preinitiation complexes (PICs) that forms biomolecular condensates through an intrinsically disordered region (IDR) to facilitate transcription, and is implicated in the function of estrogen receptor α (hereafter ER) in ER-positive breast cancer (ER+ BC) cells. We found that MED1 is acetylated at 6 lysines in its IDR and, further, that MCF7 ER+ BC cells in which endogenous MED1 is replaced by an ectopic 6KR (non-acetylatable) mutant (6KR cells) exhibit enhanced cell growth and elevated expression of MED1-dependent genes. These results indicate an enhanced function of 6KR MED1 that may be attributed to two mechanisms: (1) reorganized PIC assembly, as indicated by increased MED1 and Pol II, decreased MED17, and equivalent ERα occupancies on chromatin, particularly at active enhancers and promoters; (2) sub-TAD chromatin unfolding, as revealed by HiCAR (Hi-C on accessible regulatory DNA) analyses. Furthermore, in vitro assays demonstrate distinct physio-chemical properties of liquid-liquid phase separation (LLPS) for 6KR versus 6KQ MED1 IDRs, and for non-acetylated versus CBP-acetylated WT MED1 IDR fragments. Related, Pol II CTD heptads are sequestered in 6KR and control WT MED1 IDR condensates, but not 6KQ and CBP-acetylated WT MED1 IDR condensates. These findings, in conjunction with recent reports of PIC structures, indicate that MED1 coordinates reorganization of the PIC machinery and the rewiring of regional chromatin organization through acetylation of its IDR. This study leads to an understanding of how the transition in phase behavior of a transcription cofactor acts as a mechanistic hub integrating linear and spatial chromatin functions to support gene expression, and have potential therapeutic implications for diseases involving MED1/Mediator-mediated transcription control.

Application and effect of tension-reducing suture in surgical treatment of hypertrophic scar.

PURPOSE: To investigate the application and effectiveness of tension-reducing suture in the repair of hypertrophic scars. METHODS: A retrospective analysis of clinical data was conducted on 82 patients with hypertrophic scars treated at the Department of Burns and Plastic Surgery of Nanjing Drum Tower Hospital from September 2021 to December 2022. Patients were operated with combination of heart-shaped tension-reducing suturing technique and looped, broad, and deep buried (LBD) suturing technique or conventional suture method. Outcomes of surgical treatment were assessed before and 6 months after surgery using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). RESULTS: Improvements were achieved on scar quality compared to that preoperatively, with a reduction in scar width (1.7 ± 0.6 cm vs. 0.7 ± 0.2 cm, P < 0.001). Assessment using the POSAS and VSS scales showed significant improvements in each single parameter and total score compared to preoperative values (P < 0.05). The Combination method group achieved better score in total score of VSS scale, in color, stiffness, thickness and overall opinion of PSAS scale, and in vascularity, thickness, pliability and overall opinion of OSAS scale. CONCLUSION: The amalgamation of the heart-shaped tension-reducing suturing technique and the LBD suturing technique has shown promising outcomes, garnering notably high levels of patient satisfaction in the context of hypertrophic scar repair. Patients have exhibited favorable postoperative recoveries, underscoring the clinical merit and the prospective broader applicability of this approach in the realm of hypertrophic scar management.

Aluminum and polyanion-doping to improve structural and moisture stability of Ni-rich layered oxides for lithium-ion batteries.

Ni-rich layered materials LiNi0.8Co0.1Mn0.1O2 attracts extensive interest to build high-performance lithium-ion batteries, but ground challenges, e.g., unfavorable phase transfer and interfacial parasitic reactions during cycling, especially after being exposure to the air for a long time, greatly limit their practical utilization. Here, we prove that those issues of Ni-rich layered materials can be alleviated by concurrently incorporating the Al3+ and PO34-, and conduct corresponding comprehensive studies to explore mechanisms of the enhanced electrochemical performances. It is suggested that the phase transition (H2 to H3) that related to the lattice contraction can be suppressed after Al3+ and PO34- co-doping, leading to improved cycling stability. Additionally, the co-doping successfully mitigates the chemical reaction between the Ni-based oxides and the ambient air, significantly improving the reversibility of lithium intercalation and charge transfer kinetics against long-time storage. Specifically, the Al3+ and PO34- co-doped material maintains 94.1% capacity retention of 150 cycles before storage, and 73.6% capacity retention of 100 cycles after being stored in ambient air for 30 days, which is much better than that of the undoped one.

Exposure to microplastics renders immunity of the thick-shell mussel more vulnerable to diarrhetic shellfish toxin-producing harmful algae.

Despite both microplastics (MPs) and harmful algae blooms (HABs) may pose a severe threat to the immunity of marine bivalves, the toxification mechanism underlying is far from being fully understood. In addition, owing to the prevalence and sudden occurrence characteristics of MPs and HABs, respectively, bivalves with MP-exposure experience may face acute challenge of harmful algae under realistic scenarios. However, little is known about the impacts and underlying mechanisms of MP-exposure experience on the susceptibility of immunity to HABs in bivalve mollusks. Taking polystyrene MPs and diarrhetic shellfish toxin-producing Prorocentrum lima as representatives, the impacts of MP-exposure on immunity vulnerability to HABs were investigated in the thick-shell mussel, Mytilus coruscus. Our results revealed evident immunotoxicity of MPs and P. lima to the mussel, as evidenced by significantly impaired total count, phagocytic activity, and cell viability of haemocytes, which may result from the induction of oxidative stress, aggravation of haemocyte apoptosis, and shortage in cellular energy supply. Moreover, marked disruptions of immunity, antioxidant system, apoptosis regulation, and metabolism upon MPs and P. lima exposure were illustrated by gene expression and comparative metabolomic analyses. Furthermore, the mussels that experienced MP-exposure were shown to be more vulnerable to P. lima, indicated by greater degree of deleterious effects on abovementioned parameters detected. In general, our findings emphasize the threat of MPs and HABs to bivalve species, which deserves close attention and more investigation.

Platelet-to-Lymphocyte Ratio (PLR), Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), and Eosinophil-to-Lymphocyte Ratio (ELR) as Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD).

Purpose: The study comprehensively evaluated the prognostic roles of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and eosinophil-to-lymphocyte ratio (ELR) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients and Methods: Six hundred and nineteen patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics of the patients with AECOPD and the complete blood counts (CBCs) of the healthy volunteers were collected. The associations of PLR, NLR, MLR, BLR, and ELR with airflow limitation, hospital length of stay (LOS), C-reactive protein (CRP), and in-hospital mortality in patients with AECOPD were analyzed. Results: Compared with the healthy volunteers, PLR, NLR, MLR, BLR, and ELR were all elevated in COPD patients under stable condition. PLR, NLR, MLR, and BLR were further elevated while ELR was lowered during exacerbation. In the patients with AECOPD, PLR, NLR, and MLR were positively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more severe airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while elevated ELR was associated with decreased in-hospital mortality. Binary logistic regression analysis showed that smoking history, FEV1% predicted, pneumonia, pulmonary heart disease (PHD), uric acid (UA), albumin, and MLR were significant independent predictors ofin-hospital mortality. These predictors along with ELR were used to construct a nomogram for predicting in-hospital mortality in AECOPD. The nomogram had a C-index of 0.850 (95% CI: 0.799-0.901), and the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) further demonstrated its good predictive value and clinical applicability. Conclusion: In summary, PLR, NLR, MLR, and ELR served as useful biomarkers in patients with AECOPD.

A density functional theory study on the mechanism of toluene from dimethylcyclopentane catalyzed by the [GaH]2+ active site of Ga-ZSM-5.

The ONIOM (ωb97xd/6-31G(d,p):pm6) method was used to study the reaction mechanism of dimethylcyclopentane to toluene by the [GaH]2+ active site of Ga-ZSM-5. The results showed that the rate-determining step in the dimethylcyclopentane aromatization process is the ring expansion process. Compared to those of methylcyclopentane to benzene (D. D. Zhang, H. Y. Liu, L. X. Ling, H. R. Zhang, R. G. Zhang, P. Liu and B. J. Wang, Phys. Chem. Chem. Phys., 2021, 23, 10988-11003.), the free energy barriers of dimethylcyclopentane to toluene are significantly decreased, indicating that toluene is easier to produce than benzene, which confirmed the experimental results that a higher proportion of toluene than benzene is produced in the MTA process.

Enhancing the reversibility of the chemical evolution of the Ni-rich LiNi0.8Co0.1Mn0.1O2 cathode via a simple pre-oxidation process.

For developing commercially viable LiNi1-x-yMnxCoyO2 (NCM), it is necessary to alleviate the irreversible chemical process upon Li-ion insertion/extraction, which primarily accounts for prevailing capacity loss, impedance buildup as well as low columbic efficiency. To resolve this issue, we herein propose a simple but novel method to alter the chemical composition by a facile treatment of H2O2, which remarkably reduces the cation mixing of Li+/Ni2+ and residual lithium on the cathode. The tailored composition contributes great resistance to the structural reconstruction and enhancement in structural reversibility, as shown by in situ Raman and high-resolution transmission electron microscope (HRTEM) results. Thus, the modified sample outperforms the pristine one; it exhibits cyclability with 95.7% capacity retention over 300 cycles, high columbic efficiency and enhanced rate capability.

Potent inhibitors targeting cyclin-dependent kinase 9 discovered via virtual high-throughput screening and absolute binding free energy calculations.

Due to the crucial regulatory mechanism of cyclin-dependent kinase 9 (CDK9) in mRNA transcription, the development of kinase inhibitors targeting CDK9 holds promise as a potential treatment strategy for cancer. A structure-based virtual screening approach has been employed for the discovery of potential novel CDK9 inhibitors. First, compounds with kinase inhibitor characteristics were identified from the ZINC15 database via virtual high-throughput screening. Next, the predicted binding modes were optimized by molecular dynamics simulations, followed by precise estimation of binding affinities using absolute binding free energy calculations based on the free energy perturbation scheme. The binding mode of molecule 006 underwent an inward-to-outward flipping, and the new binding mode exhibited binding affinity comparable to the small molecule T6Q in the crystal structure (PDB ID: 4BCF), highlighting the essential role of molecular dynamics simulation in capturing a plausible binding pose bridging docking and absolute binding free energy calculations. Finally, structural modifications based on these findings further enhanced the binding affinity with CDK9. The results revealed that enhancing the molecule's rigidity through ring formation, while maintaining the major interactions, reduced the entropy loss during the binding process and, thus, enhanced binding affinities.

Single-cell RNA sequencing analysis of lung cells in COVID-19 patients with diabetes, hypertension, and comorbid diabetes-hypertension.

Background: There is growing evidence that the lung is a target organ for injury in diabetes and hypertension. There are no studies on the status of the lungs, especially cellular subpopulations, and related functions in patients with diabetes, hypertension, and hypertension-diabetes after combined SARS-CoV-2 infection. Method: Using single-cell meta-analysis in combination with bulk-RNA analysis, we identified three drug targets and potential receptors for SARS-CoV-2 infection in lung tissues from patients with diabetes, hypertension, and hypertension-diabetes, referred to as "co-morbid" patients. Using single-cell meta-analysis analysis in combination with bulk-RNA, we identified drug targets and potential receptors for SARS-CoV-2 infection in the three co-morbidities. Results: The single-cell meta-analysis of lung samples from SARS-CoV-2-infected individuals with diabetes, hypertension, and hypertension-diabetes comorbidity revealed an upregulation of fibroblast subpopulations in these disease conditions associated with a predictive decrease in lung function. To further investigate the response of fibroblasts to therapeutic targets in hypertension and diabetes, we analyzed 35 upregulated targets in both diabetes and hypertension. Interestingly, among these targets, five specific genes were upregulated in fibroblasts, suggesting their potential association with enhanced activation of endothelial cells. Furthermore, our investigation into the underlying mechanisms driving fibroblast upregulation indicated that KREMEN1, rather than ACE2, could be the receptor responsible for fibroblast activation. This finding adds novel insights into the molecular processes involved in fibroblast modulation in the context of SARS-CoV-2 infection within these comorbid conditions. Lastly, we compared the efficacy of Pirfenidone and Nintedanib as therapeutic interventions targeting fibroblasts prone to pulmonary fibrosis. Our findings suggest that Nintedanib may be a more suitable treatment option for COVID-19 patients with diabetes and hypertension who exhibit fibrotic lung lesions. Conclusion: In the context of SARS-CoV-2 infections, diabetes, hypertension, and their coexistence predominantly lead to myofibroblast proliferation. This phenomenon could be attributed to the upregulation of activated endothelial cells. Moreover, it is noteworthy that therapeutic interventions targeting hypertension-diabetes demonstrate superior efficacy. Regarding treating fibrotic lung conditions, Nintedanib is a more compelling therapeutic option.